{"id": "PMID:1253462", "title": "Value of the erythrocyte sedimentation rate in gynecologic infections.", "content": "The ESR remains a valuable test in gynecology, specifically when obtained sequentially in cases of pelvic infection. It is nonspecific but has much merit in assessing prognosis and therapeutic measures. In conjunction with laparoscopy and diagnostic ultrasound it plays an important part in the evaluation of abdominal and pelvic infections.", "contents": "Value of the erythrocyte sedimentation rate in gynecologic infections. The ESR remains a valuable test in gynecology, specifically when obtained sequentially in cases of pelvic infection. It is nonspecific but has much merit in assessing prognosis and therapeutic measures. In conjunction with laparoscopy and diagnostic ultrasound it plays an important part in the evaluation of abdominal and pelvic infections."} {"id": "PMID:1253470", "title": "Accurate roentgenographic determination of lumbar flexion-extension.", "content": "Although many techniques have been devised for the roentgenographic measurement for angular motion in the lumbar spine, all present technical and visual problems. No previously described method has been subjected to a test of accuracy or reliability. A transparent plastic sheet technique provides a reproducible and accurate method for quantitative evaluation of flexion-extension motion in the lumbar spine.", "contents": "Accurate roentgenographic determination of lumbar flexion-extension. Although many techniques have been devised for the roentgenographic measurement for angular motion in the lumbar spine, all present technical and visual problems. No previously described method has been subjected to a test of accuracy or reliability. A transparent plastic sheet technique provides a reproducible and accurate method for quantitative evaluation of flexion-extension motion in the lumbar spine."} {"id": "PMID:1253473", "title": "Isolated lumbar disk resorption as a cause of nerve root canal stenosis.", "content": "In established isolated disk resorption at the lumbo-sacral junction, nerve root canal stenosis affects predominantly the S1 nerve which becomes obstructed between the inner margin of the superior facet of S1 and the buckled ligamentum flavum behind and by the ridge of the remaining annular fibers in front. However, in addition, there may also be an intervertebral foramen stenosis involving the L5 nerve at this level. Accordingly, in planning the surgical treatment of this condition where bilateral buttock and leg pain has become intractable or frequently recurrent, and where back pain is not major concomitant of the symptom complex, the surgeon must remove the inner and superior margins of the S1 facet together with the whole of the ligamentum flavum, thereby decompressing both L5 and S1 nerve roots. The operation involves a partial facetectomy only at the affected level and spinal stability is not impaired.", "contents": "Isolated lumbar disk resorption as a cause of nerve root canal stenosis. In established isolated disk resorption at the lumbo-sacral junction, nerve root canal stenosis affects predominantly the S1 nerve which becomes obstructed between the inner margin of the superior facet of S1 and the buckled ligamentum flavum behind and by the ridge of the remaining annular fibers in front. However, in addition, there may also be an intervertebral foramen stenosis involving the L5 nerve at this level. Accordingly, in planning the surgical treatment of this condition where bilateral buttock and leg pain has become intractable or frequently recurrent, and where back pain is not major concomitant of the symptom complex, the surgeon must remove the inner and superior margins of the S1 facet together with the whole of the ligamentum flavum, thereby decompressing both L5 and S1 nerve roots. The operation involves a partial facetectomy only at the affected level and spinal stability is not impaired."} {"id": "PMID:1253474", "title": "Stenosis of the lumbar spine in spondylolisthesis.", "content": "There are three factors which determine the volume of the spinal canal, its lateral recesses and the intervertebral canals; the developmental size; the level cephalad and caudad of the vertebral column; the multiple acquired conditions which may cause encroachment. The causes of narrowing in spondylolisthesis are characteristic of each type. Three common groups are mentioned, congenital, isthmic and degenerative and the nature of obstruction and its appropriate treatment is described in each case.", "contents": "Stenosis of the lumbar spine in spondylolisthesis. There are three factors which determine the volume of the spinal canal, its lateral recesses and the intervertebral canals; the developmental size; the level cephalad and caudad of the vertebral column; the multiple acquired conditions which may cause encroachment. The causes of narrowing in spondylolisthesis are characteristic of each type. Three common groups are mentioned, congenital, isthmic and degenerative and the nature of obstruction and its appropriate treatment is described in each case."} {"id": "PMID:1253472", "title": "Spinal stenosis. Results of treatment.", "content": "Seventy patients with spinal stenosis are reported according to the new international classifications. Cases where the stenosis was caused mainly by interluminar lesions such as disk protrusion are excluded. The treatment of patients with segmental disease and adequate technical decompression was generally successful while the patients with more generalized disease had less predictable end results. In spite of wide decompression of the lateral gutter of the spinal canal, there was little tendency to further olisthesis except in the degenerative spondylolisthesis group. Spinal fusion did not appear to be necessary except in this latter group of patients. Technetium polyphosphate scanning techniques have shown an active process in the facet joints of the spondylolisthesis group with degenerative disease.", "contents": "Spinal stenosis. Results of treatment. Seventy patients with spinal stenosis are reported according to the new international classifications. Cases where the stenosis was caused mainly by interluminar lesions such as disk protrusion are excluded. The treatment of patients with segmental disease and adequate technical decompression was generally successful while the patients with more generalized disease had less predictable end results. In spite of wide decompression of the lateral gutter of the spinal canal, there was little tendency to further olisthesis except in the degenerative spondylolisthesis group. Spinal fusion did not appear to be necessary except in this latter group of patients. Technetium polyphosphate scanning techniques have shown an active process in the facet joints of the spondylolisthesis group with degenerative disease."} {"id": "PMID:1253477", "title": "Fibrous spinal stenosis. A report on 850 myelograms with a water-soluble contrast medium.", "content": "Although osseous spinal stenosis was rarely seen, fibrous spinal stenosis was demonstrated in 6% of 850 lumbar myelograms done with 10 ml doses of water-soluble Dimer-X (Maybaker). The common antecedents of fibrosis were myelography with an oily medium and spinal operations. In mild affections only the nerve root sheaths were obliterated. More severe fibrosis produced additional stenosis of a segment of the thecal sac.", "contents": "Fibrous spinal stenosis. A report on 850 myelograms with a water-soluble contrast medium. Although osseous spinal stenosis was rarely seen, fibrous spinal stenosis was demonstrated in 6% of 850 lumbar myelograms done with 10 ml doses of water-soluble Dimer-X (Maybaker). The common antecedents of fibrosis were myelography with an oily medium and spinal operations. In mild affections only the nerve root sheaths were obliterated. More severe fibrosis produced additional stenosis of a segment of the thecal sac."} {"id": "PMID:1253475", "title": "Degenerative spondylolisthesis.", "content": "Degenerative spondylolisthesis is one important type of spinal stenosis. The spinal canal stenosis varies in degree. This is the result of anterior slipping of the whole vertebra, usually L4 on L5. The clinical picture is not greatly different from that observed in the other types of lumbar canal stenosis. The surgical management involves decompression of the cauda equina by laminectomy. Often this is associated with arthrectomy to decompress the nerve roots. Extensive excision of the neural arch may result in further spinal instability for which spinal fusion is generally advisable.", "contents": "Degenerative spondylolisthesis. Degenerative spondylolisthesis is one important type of spinal stenosis. The spinal canal stenosis varies in degree. This is the result of anterior slipping of the whole vertebra, usually L4 on L5. The clinical picture is not greatly different from that observed in the other types of lumbar canal stenosis. The surgical management involves decompression of the cauda equina by laminectomy. Often this is associated with arthrectomy to decompress the nerve roots. Extensive excision of the neural arch may result in further spinal instability for which spinal fusion is generally advisable."} {"id": "PMID:1253479", "title": "Fracture after arthrodesis of the hip and knee.", "content": "In 27 cases of fracture after arthrodesis of the hip and knee, there was a characteristic location and appearance which depended upon whether or not metal implant was present. Fracture healing and preservation of motion of adjacent joints was achieved in all cases with internal fixation using the plating techniques described by the A-O group. There is also always the opportunity to decorticate and add supplementary bone grafts for an arthrodesis that had failed before the time of fracture. Metal implants should be removed when there is evidence of consolidation and maturation of bone at both the arthrodesis and fracture sites.", "contents": "Fracture after arthrodesis of the hip and knee. In 27 cases of fracture after arthrodesis of the hip and knee, there was a characteristic location and appearance which depended upon whether or not metal implant was present. Fracture healing and preservation of motion of adjacent joints was achieved in all cases with internal fixation using the plating techniques described by the A-O group. There is also always the opportunity to decorticate and add supplementary bone grafts for an arthrodesis that had failed before the time of fracture. Metal implants should be removed when there is evidence of consolidation and maturation of bone at both the arthrodesis and fracture sites."} {"id": "PMID:1253476", "title": "Post-laminectomy and post-fusion stenosis of the lumbar spine.", "content": "On the basis of a 9-year experience with 231 patients with post-laminectomy and post-spinal fusion stenosis of the lumbar spinal canal, we emphasize the importance of recognizing and adequately decompressing such lesions. In the majority of such patients pain relief has been achieved, but some of the failures can be attributed to technical reasons. Most failures are due to associated lesions and to functional factors. A special surgical techniy be advisable. The indications for fusion however were few and require further investigation and evaluation. The significant failure rate points to the need for continuing research into the causes of low back pain and adequate management programs for the patient with the \"multiple operated back\" who still has disabling pain and drug dependence.", "contents": "Post-laminectomy and post-fusion stenosis of the lumbar spine. On the basis of a 9-year experience with 231 patients with post-laminectomy and post-spinal fusion stenosis of the lumbar spinal canal, we emphasize the importance of recognizing and adequately decompressing such lesions. In the majority of such patients pain relief has been achieved, but some of the failures can be attributed to technical reasons. Most failures are due to associated lesions and to functional factors. A special surgical techniy be advisable. The indications for fusion however were few and require further investigation and evaluation. The significant failure rate points to the need for continuing research into the causes of low back pain and adequate management programs for the patient with the \"multiple operated back\" who still has disabling pain and drug dependence."} {"id": "PMID:1253478", "title": "Diffuse pigmented villonodular synovitis. An indication for total hip replacement in the young patient.", "content": "Diffuse pigmented villonodular synovitis of the hip is a special problem because in this location it uniformly results in severe bony and cartilaginous destruction of the joint. In 2 cases treated by total hip replacement, both were successful at periods longer than 1 and 3 years follow-up with no evidence of recurrence of the disease, prosthetic failure, loosening, or any other complication despite the patients' young age and extremely active life styles. Continuous follow-up and frequent admonition about the wear erosion and recurrences of the synovitis is an essential part of the aftercare of these patients.", "contents": "Diffuse pigmented villonodular synovitis. An indication for total hip replacement in the young patient. Diffuse pigmented villonodular synovitis of the hip is a special problem because in this location it uniformly results in severe bony and cartilaginous destruction of the joint. In 2 cases treated by total hip replacement, both were successful at periods longer than 1 and 3 years follow-up with no evidence of recurrence of the disease, prosthetic failure, loosening, or any other complication despite the patients' young age and extremely active life styles. Continuous follow-up and frequent admonition about the wear erosion and recurrences of the synovitis is an essential part of the aftercare of these patients."} {"id": "PMID:1253481", "title": "Abduction injuries of the distal femoral epiphysis.", "content": "Based on a follow-up study of 15 distal femoral epiphyseal fractures, the following conclusions are drawn: Closed reduction with cross pinning of the distal femoral epiphysis provided slightly better results and prevented loss of reduction; angulation deformity, requiring corrective surgery occurred in four patients, two of whom had initial anatomical reductions; significant leg length inequality was not seen; abduction injuries of the distal femoral epiphysis are not uncommon in teenage football players.", "contents": "Abduction injuries of the distal femoral epiphysis. Based on a follow-up study of 15 distal femoral epiphyseal fractures, the following conclusions are drawn: Closed reduction with cross pinning of the distal femoral epiphysis provided slightly better results and prevented loss of reduction; angulation deformity, requiring corrective surgery occurred in four patients, two of whom had initial anatomical reductions; significant leg length inequality was not seen; abduction injuries of the distal femoral epiphysis are not uncommon in teenage football players."} {"id": "PMID:1253480", "title": "Technique, errors and safeguards in modern K\u00fcntscher nailing.", "content": "Intramedullary nailing after reaming of the medullary cavity according to K\u00fcntscher, provides a rigid fixation and makes early mobilization possible, and is even applicable to infected non-unions. Experience with 150 cases of fresh femoral fractures and more than 80 cases of non-union of the femur, the tibia, the humerus and the forearm, demonstrates that thorough familiarity with the instrumentation and the pitfalls of the technique, as well as the correct clinical indications of the method are critical to the achievement of good results.", "contents": "Technique, errors and safeguards in modern K\u00fcntscher nailing. Intramedullary nailing after reaming of the medullary cavity according to K\u00fcntscher, provides a rigid fixation and makes early mobilization possible, and is even applicable to infected non-unions. Experience with 150 cases of fresh femoral fractures and more than 80 cases of non-union of the femur, the tibia, the humerus and the forearm, demonstrates that thorough familiarity with the instrumentation and the pitfalls of the technique, as well as the correct clinical indications of the method are critical to the achievement of good results."} {"id": "PMID:1253482", "title": "Fat embolism following bilateral total knee replacement with the Guepar prosthesis. A case report.", "content": "Fat embolism followed bilateral total knee replacement with Guepar prostheses in a rheumatoid patient the day after the operation. The risk of fat embolism following total knee replacement with a hinge prosthesis is especially high in rheumatoid patients with compromised pulmonary functions and a history of long-term treatment with corticosteroids.", "contents": "Fat embolism following bilateral total knee replacement with the Guepar prosthesis. A case report. Fat embolism followed bilateral total knee replacement with Guepar prostheses in a rheumatoid patient the day after the operation. The risk of fat embolism following total knee replacement with a hinge prosthesis is especially high in rheumatoid patients with compromised pulmonary functions and a history of long-term treatment with corticosteroids."} {"id": "PMID:1253485", "title": "Isolated partial tear of the anterior cruciate ligament.", "content": "Isolated partial tear of the anterior cruciate ligament should be suspected in the patient with effusion, flexion contracture and poorly localized pain and tenderness following a knee injury. The diagnosis is difficult to make from physical findings or even arthrography. Arthroscopy is helpful in making the diagnosis and in ruling out associated meniscus lesions. A normal meniscus should not be removed if this seemingly trivial lesion is the only abnormal finding at arthrotomy. Surgical treatment is not necessary if the diagnosis can be made by other means. This injury responds well to immobilization in extension followed by rehabilitation.", "contents": "Isolated partial tear of the anterior cruciate ligament. Isolated partial tear of the anterior cruciate ligament should be suspected in the patient with effusion, flexion contracture and poorly localized pain and tenderness following a knee injury. The diagnosis is difficult to make from physical findings or even arthrography. Arthroscopy is helpful in making the diagnosis and in ruling out associated meniscus lesions. A normal meniscus should not be removed if this seemingly trivial lesion is the only abnormal finding at arthrotomy. Surgical treatment is not necessary if the diagnosis can be made by other means. This injury responds well to immobilization in extension followed by rehabilitation."} {"id": "PMID:1253484", "title": "Management of patellar subluxation. A modification of Hauser's technique.", "content": "Patellar subluxation is one of the most common causes of internal derangement of the knee in young individuals. Most surgical techniques mandate entrance into the knee joint and require prolonged postoperative immobilization. The result may be excessive postoperative synovitis and occasionally, hemarthrosis. Prolonged postoperative immobilization results in joint stiffness. The authors propose a modification of Hauser's technique which allows tailored correction of the abnormal vector forces applied to the patella, simple adjustment of the tension in the extensor mechanism, creates patellar stability, and permits rapid return of knee motion. A new tibial corticocancellous window is created in a manner similar to Hauser's technique. The cancellous defect is deepened by curettage and the transferred tibial tubercle is then inverted, inserted through the window, and tamped into the graft bed thereby gradually increasing tension in the tendon. The cancellous and cortical bone from the window is then tamped in behind the patella tendon, buttressing the tendon, and permitting the knee a full unguarded range of motion on the operating table. In 23 operations in 22 patients, with a follow-up of 35.4 months and a mean patient age of 18.7 years, all patellae were stable. All but one patient achieved full range of motion. Younger patients with minimal or absent preoperative patellofemoral chondromalacia had uniformly good results.", "contents": "Management of patellar subluxation. A modification of Hauser's technique. Patellar subluxation is one of the most common causes of internal derangement of the knee in young individuals. Most surgical techniques mandate entrance into the knee joint and require prolonged postoperative immobilization. The result may be excessive postoperative synovitis and occasionally, hemarthrosis. Prolonged postoperative immobilization results in joint stiffness. The authors propose a modification of Hauser's technique which allows tailored correction of the abnormal vector forces applied to the patella, simple adjustment of the tension in the extensor mechanism, creates patellar stability, and permits rapid return of knee motion. A new tibial corticocancellous window is created in a manner similar to Hauser's technique. The cancellous defect is deepened by curettage and the transferred tibial tubercle is then inverted, inserted through the window, and tamped into the graft bed thereby gradually increasing tension in the tendon. The cancellous and cortical bone from the window is then tamped in behind the patella tendon, buttressing the tendon, and permitting the knee a full unguarded range of motion on the operating table. In 23 operations in 22 patients, with a follow-up of 35.4 months and a mean patient age of 18.7 years, all patellae were stable. All but one patient achieved full range of motion. Younger patients with minimal or absent preoperative patellofemoral chondromalacia had uniformly good results."} {"id": "PMID:1253487", "title": "Giant synovial cyst of the calf and thigh in a patient with granulomatous synovitis.", "content": "A giant synovial cyst with granulomatous synovitis was removed from the thigh and calf in an 80-year-old woman. The lesion included necrotizing, epitheloid cell granulomata with Langhans' type giant cells. Chest X-ray, tuberculin testing, cultures for Acid Fast bacilli, as well as aerobic, anaerobic and fungal cultures were all negative. The treatment consisted of synovectomy and total knee arthroplasty with an uneventful recovery. A giant calf cyst, usually associated with rheumatoid arthritis, but in this situation, noted in granulomatous synovitis seems not to have been reported previously.", "contents": "Giant synovial cyst of the calf and thigh in a patient with granulomatous synovitis. A giant synovial cyst with granulomatous synovitis was removed from the thigh and calf in an 80-year-old woman. The lesion included necrotizing, epitheloid cell granulomata with Langhans' type giant cells. Chest X-ray, tuberculin testing, cultures for Acid Fast bacilli, as well as aerobic, anaerobic and fungal cultures were all negative. The treatment consisted of synovectomy and total knee arthroplasty with an uneventful recovery. A giant calf cyst, usually associated with rheumatoid arthritis, but in this situation, noted in granulomatous synovitis seems not to have been reported previously."} {"id": "PMID:1253486", "title": "Arteries and veins of the lumbar nerve roots and cauda equina.", "content": "An abundant vascular system supplies the nerve roots, within the cauda equina, in the spinal canal and in the nerve root tunnels. The arterial supply of nervous tissue, as noted by previous observers, is \"just adequate for its minimal needs.\" The veins of the area are classified into 3 groups, those of the spinal canal within the extradural space, those of the nerve roots themselves (radicular veins) and those which drain the bony skeleton. These thin-walled venous channels are a source of serious bleeding both at operation and in the postoperative period. Elsewhere in this symposium, emphasis has been placed on the way in which spinal stenosis and pressure on nerves cause the complex group of symptoms. Pressure on arteries, veins and capillaries can impair nerve conduction, with changes in sensation and loss of motor power in one or both limbs. If the pressure is prolonged, irreversible changes take place in the substance of the nerve roots. Recovery of sensation and of motor power following adequate surgical decompression will then be incomplete.", "contents": "Arteries and veins of the lumbar nerve roots and cauda equina. An abundant vascular system supplies the nerve roots, within the cauda equina, in the spinal canal and in the nerve root tunnels. The arterial supply of nervous tissue, as noted by previous observers, is \"just adequate for its minimal needs.\" The veins of the area are classified into 3 groups, those of the spinal canal within the extradural space, those of the nerve roots themselves (radicular veins) and those which drain the bony skeleton. These thin-walled venous channels are a source of serious bleeding both at operation and in the postoperative period. Elsewhere in this symposium, emphasis has been placed on the way in which spinal stenosis and pressure on nerves cause the complex group of symptoms. Pressure on arteries, veins and capillaries can impair nerve conduction, with changes in sensation and loss of motor power in one or both limbs. If the pressure is prolonged, irreversible changes take place in the substance of the nerve roots. Recovery of sensation and of motor power following adequate surgical decompression will then be incomplete."} {"id": "PMID:1253489", "title": "Functional treatment of intra-articular fractures of the calcaneus.", "content": "Fifty-one adult patients with 54 intra-articular fractures of the calcaneus have been reviewed from one to 11 years after the injury. Treatment consisted in immediate active exercises of the foot without any attempt at reduction or immobilization. The patients resumed full weight-bearing, on the average, three months after injury. The overall results were excellent in 19, good in 24 and unsatisfactory, objectively and subjectively, in 11 feet. In this consecutive series, the majority of the fractures had a marked degree of displacement. Excluding undisplaced fractures which had a good result, no clear cut relation between the type and degree of displacement and the final result could be found. However, there were more unsatisfactory results in fractures in which the tuber-joint angle was equal to or less than 10 degrees.", "contents": "Functional treatment of intra-articular fractures of the calcaneus. Fifty-one adult patients with 54 intra-articular fractures of the calcaneus have been reviewed from one to 11 years after the injury. Treatment consisted in immediate active exercises of the foot without any attempt at reduction or immobilization. The patients resumed full weight-bearing, on the average, three months after injury. The overall results were excellent in 19, good in 24 and unsatisfactory, objectively and subjectively, in 11 feet. In this consecutive series, the majority of the fractures had a marked degree of displacement. Excluding undisplaced fractures which had a good result, no clear cut relation between the type and degree of displacement and the final result could be found. However, there were more unsatisfactory results in fractures in which the tuber-joint angle was equal to or less than 10 degrees."} {"id": "PMID:1253488", "title": "Advancement of the tibial tuberosity.", "content": "Surgical modifications of the biomechanics of osteoarthritic and chondromalacic patellofemoral joints reduce the joint pressure by distributing pressure evenly along the articular surfaces. Forward displacement of the patella tendon lengthens the lever arm of the tendon. It also increases the angle formed by the forces exerted by the quadriceps muscle and by the patella tendon. As a result, the compressive forces transmitted from the femur to the tibia and from the patella to the femur are decreased. If the anterior tuberosity of the tibia is displaced forward and medially, the subluxated patella is brought back into the intercondylar groove and the weight-bearing areas of the patello-femoral joint are increased. Consequently the operation much reduces the compressive stresses in the joint. In osteoarthritis of the patellofemoral joint and in chondromalacia of the patella, surgical displacement of the patella tendon forward consistently relieved pain.", "contents": "Advancement of the tibial tuberosity. Surgical modifications of the biomechanics of osteoarthritic and chondromalacic patellofemoral joints reduce the joint pressure by distributing pressure evenly along the articular surfaces. Forward displacement of the patella tendon lengthens the lever arm of the tendon. It also increases the angle formed by the forces exerted by the quadriceps muscle and by the patella tendon. As a result, the compressive forces transmitted from the femur to the tibia and from the patella to the femur are decreased. If the anterior tuberosity of the tibia is displaced forward and medially, the subluxated patella is brought back into the intercondylar groove and the weight-bearing areas of the patello-femoral joint are increased. Consequently the operation much reduces the compressive stresses in the joint. In osteoarthritis of the patellofemoral joint and in chondromalacia of the patella, surgical displacement of the patella tendon forward consistently relieved pain."} {"id": "PMID:1253491", "title": "Hormonal effects on the morphology of bone defect healing.", "content": "Standard defects were produced in the radii of hypophysectomized immature rats. All animals were injected with Methimazole, and grouped according to hormone supplementation, growth hormone (GH), thyroxine (T4), the combination, or no hormones. Lack of GH and T4 caused a retardation of defect healing and callus formation but not a total cessation. The presence of GH in the hypophysectomized animal caused a larger callus due to greatly increased chondrogenesis throughout the 6 week study. Thyroxine in the hypophysectomized animal increased bone metabolism and caused more cartilage and bone formation than seen in the hormone deficient group, but not as great as that seen in the GH injected animals or the T4 and GH injected animals. Growth hormone allowed greater chondrogenesis; T4 enhanced maturation to bone. The combination allowed the development of a callus similar in stage and proportion of tissue to that observed in the pituitary intact animals. The influences of GH and T4 on the healing of a bone defect in the immature rat correspond to influences of GH and T4 on growing epiphyseal plate.", "contents": "Hormonal effects on the morphology of bone defect healing. Standard defects were produced in the radii of hypophysectomized immature rats. All animals were injected with Methimazole, and grouped according to hormone supplementation, growth hormone (GH), thyroxine (T4), the combination, or no hormones. Lack of GH and T4 caused a retardation of defect healing and callus formation but not a total cessation. The presence of GH in the hypophysectomized animal caused a larger callus due to greatly increased chondrogenesis throughout the 6 week study. Thyroxine in the hypophysectomized animal increased bone metabolism and caused more cartilage and bone formation than seen in the hormone deficient group, but not as great as that seen in the GH injected animals or the T4 and GH injected animals. Growth hormone allowed greater chondrogenesis; T4 enhanced maturation to bone. The combination allowed the development of a callus similar in stage and proportion of tissue to that observed in the pituitary intact animals. The influences of GH and T4 on the healing of a bone defect in the immature rat correspond to influences of GH and T4 on growing epiphyseal plate."} {"id": "PMID:1253490", "title": "Alterations in pulmonary function, coagulation and fat metabolism in patients with fractures of the lower limbs.", "content": "If the underlying pathology of the syndrome of fat embolism is the presence of circulating emboli of neutral fat with adherent platelets and red blood cells, then one could expect certain changes in normal vascular cellular elements and fat metabolism, with resultant alterations in pulmonary function. In our series of 118 patients with fractures of the lower limbs we found that more than half of them exhibited hypoxemia as well as a decrease in the hematocrit and platelet counts with a concomitant increase in platelet adhesiveness. In addition, those patients with hypoxemia showed increased fibrinogen degenerative product levels indicating an increased fibrinolysis. We found only a slight temporary rise in the serum triglycerides, but the nonesterified fatty acid levels rose sharply over the first three days following trauma associated with an increase in serum lipase. Our study demonstrated that this increase in serum lipase occurred slightly before the peaking tendency observed in the nonesterified fatty acids. Following trauma, fat emboli with adherent platelets and other vascular cellular elements are formed; we would expect that these emboli would lodge in the capillaries and small vessels of the lung, thereby producing a physiological shunt. An increase in the A-aDo2 confirmed this hypothesis and was associated with a decrease in the arterial oxygen level in over half the patients studied. Although 58 of our patients showed evidence of hypoxemia associated with a fall in hematocrit and platelet count, not one of them showed clinical signs and symptoms of the fat embolus syndrome. This study suggests that a subclinical form of fat embolism does exist. What causes a small percentage of those patients with subclinical fat embolism to progress to a clinical fat embolism is still unknown. The majority of our patients spontaneously returned to normal within 5 days. Reviewing the results of those patients who developed hypoxemia and the two patients who developed clinical fat embolism, there seems to be no indication of what causes the progression. Hypotension and shock do not seem to be relevant to the progression of the subclinical condition. Not one of 110 reviewed had evidence of shock or persistent hypotension, yet 58 of these patients developed changes in arterial saturation, vascular elements, and evidence of disseminated intravascular coagulation.", "contents": "Alterations in pulmonary function, coagulation and fat metabolism in patients with fractures of the lower limbs. If the underlying pathology of the syndrome of fat embolism is the presence of circulating emboli of neutral fat with adherent platelets and red blood cells, then one could expect certain changes in normal vascular cellular elements and fat metabolism, with resultant alterations in pulmonary function. In our series of 118 patients with fractures of the lower limbs we found that more than half of them exhibited hypoxemia as well as a decrease in the hematocrit and platelet counts with a concomitant increase in platelet adhesiveness. In addition, those patients with hypoxemia showed increased fibrinogen degenerative product levels indicating an increased fibrinolysis. We found only a slight temporary rise in the serum triglycerides, but the nonesterified fatty acid levels rose sharply over the first three days following trauma associated with an increase in serum lipase. Our study demonstrated that this increase in serum lipase occurred slightly before the peaking tendency observed in the nonesterified fatty acids. Following trauma, fat emboli with adherent platelets and other vascular cellular elements are formed; we would expect that these emboli would lodge in the capillaries and small vessels of the lung, thereby producing a physiological shunt. An increase in the A-aDo2 confirmed this hypothesis and was associated with a decrease in the arterial oxygen level in over half the patients studied. Although 58 of our patients showed evidence of hypoxemia associated with a fall in hematocrit and platelet count, not one of them showed clinical signs and symptoms of the fat embolus syndrome. This study suggests that a subclinical form of fat embolism does exist. What causes a small percentage of those patients with subclinical fat embolism to progress to a clinical fat embolism is still unknown. The majority of our patients spontaneously returned to normal within 5 days. Reviewing the results of those patients who developed hypoxemia and the two patients who developed clinical fat embolism, there seems to be no indication of what causes the progression. Hypotension and shock do not seem to be relevant to the progression of the subclinical condition. Not one of 110 reviewed had evidence of shock or persistent hypotension, yet 58 of these patients developed changes in arterial saturation, vascular elements, and evidence of disseminated intravascular coagulation."} {"id": "PMID:1253492", "title": "An ultrastructural evaluation of the effect of hydrocortisone on rabbit cartilage.", "content": "Pharmacologic and supra-pharmacologic doses of hydrocortisone acetate did not effect ultrastructural alteration of chondrocytes in articular cartilage of mature rabbits. Early biomechanical alterations are unaccompanied by ultrastructural cytological changes. Not until advanced biochemical alteration is effected by large, repetitive doses, does the ultrastructural alteration begin.", "contents": "An ultrastructural evaluation of the effect of hydrocortisone on rabbit cartilage. Pharmacologic and supra-pharmacologic doses of hydrocortisone acetate did not effect ultrastructural alteration of chondrocytes in articular cartilage of mature rabbits. Early biomechanical alterations are unaccompanied by ultrastructural cytological changes. Not until advanced biochemical alteration is effected by large, repetitive doses, does the ultrastructural alteration begin."} {"id": "PMID:1253493", "title": "Acute local tissue effects of polymerizing acrylic bone cement. An intravital microscopic study in the hamster's check pouch on the chemically induced microvascular changes.", "content": "The chemical effect of polymerizing CMW and Simplex-P bone cements was recorded by intravital microscopy in the hamster's cheek pouch. Thermal effects and pressure on the tissue were eliminated. Where a direct cement-tissue contact was present, severe, apparently irreversible, microcirculatory disturbances were recorded. Both cements caused equally extensive microvascular damage. Intact epithelium and connective tissue appeared to protect the underlying vascular bed from the effect of the monomer. No differences in tissue reaction were recorded when the cement past was applied after normal and prolonged kneading.", "contents": "Acute local tissue effects of polymerizing acrylic bone cement. An intravital microscopic study in the hamster's check pouch on the chemically induced microvascular changes. The chemical effect of polymerizing CMW and Simplex-P bone cements was recorded by intravital microscopy in the hamster's cheek pouch. Thermal effects and pressure on the tissue were eliminated. Where a direct cement-tissue contact was present, severe, apparently irreversible, microcirculatory disturbances were recorded. Both cements caused equally extensive microvascular damage. Intact epithelium and connective tissue appeared to protect the underlying vascular bed from the effect of the monomer. No differences in tissue reaction were recorded when the cement past was applied after normal and prolonged kneading."} {"id": "PMID:1253494", "title": "Innervation of the lumbar spine.", "content": "Back pain, in spinal stenosis, can arise from many sources. Apart from nerve root involvement any of the structures considered above can be implicated. In degenerative conditions, where discogenic and posterior facet pain are present, excess activity tends to increase these symptoms. In addition there is evidence that impulses reaching the spinal nerve root through the sinu-vertebral nerve and possibly the posterior ramus may potentiate the irritability of that root. Whether such a mechanism contributes to the claudication of degenerative spinal stenosis is not known.", "contents": "Innervation of the lumbar spine. Back pain, in spinal stenosis, can arise from many sources. Apart from nerve root involvement any of the structures considered above can be implicated. In degenerative conditions, where discogenic and posterior facet pain are present, excess activity tends to increase these symptoms. In addition there is evidence that impulses reaching the spinal nerve root through the sinu-vertebral nerve and possibly the posterior ramus may potentiate the irritability of that root. Whether such a mechanism contributes to the claudication of degenerative spinal stenosis is not known."} {"id": "PMID:1253496", "title": "Measurements of the lumbar spinal canal in 2 racial groups.", "content": "Direct measurements of 1,340 lumbar vertebrae in 275 skeletons in two racial groups are reported. The average figure, and the upper and lower limits of normal are reported for the anteroposterior diameter of the canal and for Spinal Index. Radiological studies have established a technique for defining the posterior margin of the spinal canal on plain X-ray films. It is formed by a line joining the apex of the superior to the inverted apex of the inferior articular facet. The Spinal Index is not a reliable factor. The anteroposterior diameter alone is the essential parameter in assessing spinal stenosis. The negroid canal is marginally less spatial than that of the caucasoid.", "contents": "Measurements of the lumbar spinal canal in 2 racial groups. Direct measurements of 1,340 lumbar vertebrae in 275 skeletons in two racial groups are reported. The average figure, and the upper and lower limits of normal are reported for the anteroposterior diameter of the canal and for Spinal Index. Radiological studies have established a technique for defining the posterior margin of the spinal canal on plain X-ray films. It is formed by a line joining the apex of the superior to the inverted apex of the inferior articular facet. The Spinal Index is not a reliable factor. The anteroposterior diameter alone is the essential parameter in assessing spinal stenosis. The negroid canal is marginally less spatial than that of the caucasoid."} {"id": "PMID:1253497", "title": "Myelography in the lumbar disk syndrome.", "content": "For myelography to convey the maximum information regarding theca size and relationships, and to avoid flow artifacts and other false positives, the theca must be filled to the L1-L2 level and X-rays taken with the patient upright thus ensuring a static column of dye.", "contents": "Myelography in the lumbar disk syndrome. For myelography to convey the maximum information regarding theca size and relationships, and to avoid flow artifacts and other false positives, the theca must be filled to the L1-L2 level and X-rays taken with the patient upright thus ensuring a static column of dye."} {"id": "PMID:1253498", "title": "Lumbar spinal stenosis. Radiographic diagnosis with special reference to transverse axial tomography.", "content": "Spinal stenosis due to malalignment and/or hypertrophy of the bony margins of the spinal canal is a recognized cause of cauda equina compression and nerve root entrapment. The plain lumbosacral spine roentgenograms reveal the number of lumbar vertebrae, their alignment, their interpedicular distances, the height of the intervertebral disk spaces and the presence of osteophyte formation. It correlates poorly with encroachment on the spinal canal. The transverse axial tomogram directly demonstrates a cross-section of the spinal canal and will show abnormal areas of bone encroachment usually arising from hypertrophied lamina and articular processes. These narrow the posterior portion of the spinal canal and encroach on the lateral recesses. This examination does not demonstrate soft tissue hypertrophy and the stenosis may be even greater than what is apparent due to the bony encroachment. The myelogram expresses how the narrowed spinal canal affects the dural sac and its contained cauda equina. Not infrequently there is an associated herniated disk.", "contents": "Lumbar spinal stenosis. Radiographic diagnosis with special reference to transverse axial tomography. Spinal stenosis due to malalignment and/or hypertrophy of the bony margins of the spinal canal is a recognized cause of cauda equina compression and nerve root entrapment. The plain lumbosacral spine roentgenograms reveal the number of lumbar vertebrae, their alignment, their interpedicular distances, the height of the intervertebral disk spaces and the presence of osteophyte formation. It correlates poorly with encroachment on the spinal canal. The transverse axial tomogram directly demonstrates a cross-section of the spinal canal and will show abnormal areas of bone encroachment usually arising from hypertrophied lamina and articular processes. These narrow the posterior portion of the spinal canal and encroach on the lateral recesses. This examination does not demonstrate soft tissue hypertrophy and the stenosis may be even greater than what is apparent due to the bony encroachment. The myelogram expresses how the narrowed spinal canal affects the dural sac and its contained cauda equina. Not infrequently there is an associated herniated disk."} {"id": "PMID:1253501", "title": "Pathological and myelographic changes in the major types of lumbar spinal stenosis.", "content": "Correlated pathological and myelographic observations suggest that the combined types of lumbar spinal stenosis appear to be the most common. The posterior articular processes play the greatest part in producing narrowing--the inferior facet narrowing the central canal and the superior facet narrowing the nerve root canal.", "contents": "Pathological and myelographic changes in the major types of lumbar spinal stenosis. Correlated pathological and myelographic observations suggest that the combined types of lumbar spinal stenosis appear to be the most common. The posterior articular processes play the greatest part in producing narrowing--the inferior facet narrowing the central canal and the superior facet narrowing the nerve root canal."} {"id": "PMID:1253500", "title": "Lumbar stenosis. An electromyographic evaluation.", "content": "Analysis of bilateral EMG and operative findings reveal that there is a definite correlation between bilateral positive EMG in particular and multiradicular EMG's and the findings of stenosis or spondylosis of the lumbar canal. Electromyography is helpful in identifying the atypical patient or the patient with unilateral symptoms who actually has bilateral pathology. The importance of a bilateral electromyographic examination is emphasized and the rarity of bilateral or multiradicular findings in simple herniated nucleus pulposus.", "contents": "Lumbar stenosis. An electromyographic evaluation. Analysis of bilateral EMG and operative findings reveal that there is a definite correlation between bilateral positive EMG in particular and multiradicular EMG's and the findings of stenosis or spondylosis of the lumbar canal. Electromyography is helpful in identifying the atypical patient or the patient with unilateral symptoms who actually has bilateral pathology. The importance of a bilateral electromyographic examination is emphasized and the rarity of bilateral or multiradicular findings in simple herniated nucleus pulposus."} {"id": "PMID:1253502", "title": "The treatment of spinal stenosis.", "content": "Decompression usually relieves leg pain and enables the patient to walk normal distances. Some back pain may remain. This is often helped by a light elastic support. If there was loss of sensation and motor power before operation, return may be considerable. The operation is only a small part of the total treatment of spinal stenosis. By relieving the pressure on nerves and blood vessels, it paves the way for the postoperative measures previously outlined. These are aimed at rebuilding atrophied muscles and restoring movement to stiff joints. We emphasize the importance of dealing not only with central stenosis involving the central canal, but also of making certain that there is no compression of the spinal nerves in their canals as they pass out through the foramina.", "contents": "The treatment of spinal stenosis. Decompression usually relieves leg pain and enables the patient to walk normal distances. Some back pain may remain. This is often helped by a light elastic support. If there was loss of sensation and motor power before operation, return may be considerable. The operation is only a small part of the total treatment of spinal stenosis. By relieving the pressure on nerves and blood vessels, it paves the way for the postoperative measures previously outlined. These are aimed at rebuilding atrophied muscles and restoring movement to stiff joints. We emphasize the importance of dealing not only with central stenosis involving the central canal, but also of making certain that there is no compression of the spinal nerves in their canals as they pass out through the foramina."} {"id": "PMID:1253506", "title": "The subspecialist and the child.", "content": "Specialty services for children may be defective because the subspecialist has not had adequate training in general pediatrics. Pediatric and pediatric surgery postgraduate programs should encourage this type of training for all subspecialists who care for children. Unless or until this occurs, the pediatrician must remain involved in the care of his patients whether their problems are primarily medical or surgical.", "contents": "The subspecialist and the child. Specialty services for children may be defective because the subspecialist has not had adequate training in general pediatrics. Pediatric and pediatric surgery postgraduate programs should encourage this type of training for all subspecialists who care for children. Unless or until this occurs, the pediatrician must remain involved in the care of his patients whether their problems are primarily medical or surgical."} {"id": "PMID:1253504", "title": "Results of decompression for lumbar spinal stenosis.", "content": "Approximately 80% of patients with spinal stenosis return to their usual occupations following decompressive laminectomy. It is essential to recognize distinctive features of stenosis on myelography and in accordance with the individual patients' clinical problems, to carry out an adequate decompression.", "contents": "Results of decompression for lumbar spinal stenosis. Approximately 80% of patients with spinal stenosis return to their usual occupations following decompressive laminectomy. It is essential to recognize distinctive features of stenosis on myelography and in accordance with the individual patients' clinical problems, to carry out an adequate decompression."} {"id": "PMID:1253509", "title": "The outcome of staphylococcal bacteremia in childhood. \"The prognosis is better than previously reported\".", "content": "Fifty infants and children were treated for staphylococcal infections complicated by bacteremia. Of these, 28 had serious underlying diseases, principally leukemia (15 cases). All were treated with intravenous antibiotics for a median duration of 12.7 days. Although 13 patients died (26%), the staphylococcal infection had apparently been eradicated in all but three (6%), one of whom died before treatment could be started. The relatively brief treatment periods required in even severely compromised leukemic patients and the survival of all but one of 22 previously healthy patients with staphylococcal bacteremia suggest that the prognosis is better than previously reported.", "contents": "The outcome of staphylococcal bacteremia in childhood. \"The prognosis is better than previously reported\". Fifty infants and children were treated for staphylococcal infections complicated by bacteremia. Of these, 28 had serious underlying diseases, principally leukemia (15 cases). All were treated with intravenous antibiotics for a median duration of 12.7 days. Although 13 patients died (26%), the staphylococcal infection had apparently been eradicated in all but three (6%), one of whom died before treatment could be started. The relatively brief treatment periods required in even severely compromised leukemic patients and the survival of all but one of 22 previously healthy patients with staphylococcal bacteremia suggest that the prognosis is better than previously reported."} {"id": "PMID:1253512", "title": "The medical and surgical management of patients with congenital heart disease. A survey of current knowledge and practices.", "content": "Today, techniques for diagnosis,medical preparation, and definitive surgical repair are available for most cardiac anomalies, if needed. These permit successful treatment and carry a low mortality. Such children can now be expected to lead normal and meaningful lives as contributors to society. When serious symptoms occur in infancy, as discussed herein, an emergency exists and prompt diagnosis and treatment are mandatory for survival.", "contents": "The medical and surgical management of patients with congenital heart disease. A survey of current knowledge and practices. Today, techniques for diagnosis,medical preparation, and definitive surgical repair are available for most cardiac anomalies, if needed. These permit successful treatment and carry a low mortality. Such children can now be expected to lead normal and meaningful lives as contributors to society. When serious symptoms occur in infancy, as discussed herein, an emergency exists and prompt diagnosis and treatment are mandatory for survival."} {"id": "PMID:1253516", "title": "Influenzavirus A2 infections presenting with febril convulsions and gastrointestinal symptoms in young children.", "content": "We present the clinical features of Influenzavirus A2 infection in 75 young children admitted to a children's hospital. The most common presenting features were febrile convulsions. vomiting, coughing, diarrhea, and anorexia. At any age, the illness may present with respiratory tract symptoms and signs but in young babies gastroinestinal symptoms are often the presenting complaint. Children aged one to three years often present with febrile convulsions. Only in older children does the adult pattern begin to emerge. Evidence is put forward to suggest that encephalitis in association with influenza can be due to direct invasion of the central nervous system by the virus.", "contents": "Influenzavirus A2 infections presenting with febril convulsions and gastrointestinal symptoms in young children. We present the clinical features of Influenzavirus A2 infection in 75 young children admitted to a children's hospital. The most common presenting features were febrile convulsions. vomiting, coughing, diarrhea, and anorexia. At any age, the illness may present with respiratory tract symptoms and signs but in young babies gastroinestinal symptoms are often the presenting complaint. Children aged one to three years often present with febrile convulsions. Only in older children does the adult pattern begin to emerge. Evidence is put forward to suggest that encephalitis in association with influenza can be due to direct invasion of the central nervous system by the virus."} {"id": "PMID:1253523", "title": "Plasma renin activity as a function of age in two new strains of spontaneously hypertensive and normotensive rats.", "content": "1. Strains of spontaneously hypertensive and normotensive rats were selected by repeated inbreeding. 2. Brief ether anesthesia was shown to produce a two- to three-fold increase in plasma renin activity in both strains. 3. Plasma renin activity was significantly higher in young spontaneously hypertensive than in normotensive rats of the same age (5-7 weeks). After the ninth week plasma renin activity decreased and, at week 45, became significantly lower in hypertensive than in normotensive rats. 4. When hypertension was established a significant inverse relationship was found between plasma renin activity and systolic blood pressure in spontaneously hypertensive and in normotensive rats. 5. It seems unlikely that the renin-angiotensin system plays a major role in the maintenance of the established spontaneous hypertension in this strain. However, renin hypersecretion may be important in the early pre-hypertensive stage of genetic hypertension in rats.", "contents": "Plasma renin activity as a function of age in two new strains of spontaneously hypertensive and normotensive rats. 1. Strains of spontaneously hypertensive and normotensive rats were selected by repeated inbreeding. 2. Brief ether anesthesia was shown to produce a two- to three-fold increase in plasma renin activity in both strains. 3. Plasma renin activity was significantly higher in young spontaneously hypertensive than in normotensive rats of the same age (5-7 weeks). After the ninth week plasma renin activity decreased and, at week 45, became significantly lower in hypertensive than in normotensive rats. 4. When hypertension was established a significant inverse relationship was found between plasma renin activity and systolic blood pressure in spontaneously hypertensive and in normotensive rats. 5. It seems unlikely that the renin-angiotensin system plays a major role in the maintenance of the established spontaneous hypertension in this strain. However, renin hypersecretion may be important in the early pre-hypertensive stage of genetic hypertension in rats."} {"id": "PMID:1253524", "title": "The functional response of the dog ileum to one hour's ischaemia.", "content": "1. The function and structure of dog ileal mucosa was examined immediately after arterial ischaemia for 1 h and 1, 3 or 7 days after the trauma. 2. Immediately after the ischaemia, there was a net movement of water and ions into a luminal perfusate in vivo. One day later, there was no net movement of water and electrolytes but net absorption returned on the third day. 3. Active transport of phenylalanine or beta-methylglucoside by mucosal strips in vitro was abolished immediately after the trauma but was largely restored 1 day later. There was a close correlation between glucose absorption in vivo and beta-methylglucoside uptake in vitro. 4. Morphological study revealed pronounced desquamation of enterocytes immediately after the trauma. The regenerating mucosa had shorter villi and crypts, and lower enzyme activities assessed histochemically 1 day later. Most parameters had returned to normal by the third post-operative day.", "contents": "The functional response of the dog ileum to one hour's ischaemia. 1. The function and structure of dog ileal mucosa was examined immediately after arterial ischaemia for 1 h and 1, 3 or 7 days after the trauma. 2. Immediately after the ischaemia, there was a net movement of water and ions into a luminal perfusate in vivo. One day later, there was no net movement of water and electrolytes but net absorption returned on the third day. 3. Active transport of phenylalanine or beta-methylglucoside by mucosal strips in vitro was abolished immediately after the trauma but was largely restored 1 day later. There was a close correlation between glucose absorption in vivo and beta-methylglucoside uptake in vitro. 4. Morphological study revealed pronounced desquamation of enterocytes immediately after the trauma. The regenerating mucosa had shorter villi and crypts, and lower enzyme activities assessed histochemically 1 day later. Most parameters had returned to normal by the third post-operative day."} {"id": "PMID:1253525", "title": "Measurement of an index of muscle capillary permeability and its correlation with serum insulin values in maturity-onset diabetic subjects.", "content": "1. An index of capillary permeability was obtained by measuring the ratio of the clearance rate of 77Br to that of 133Xe in the anterior tibial muscle, after a short period of maximal ischaemic exercise. 2. Seventeen control subjects and thirty-two maturity-onset, non-insulin-treated diabetic subjects, aged 60 years or less, were studied. Short glucose tolerance tests were performed in the diabetic subjects during which blood sugar and serum insulin concentrations were estimated. 3. The 77Br/133Xe clearance ratio was increased in the diabetic subjects compared with the control subjects. In the diabetic subjects, there was an inverse correlation between the insulin at 60 min after glucose and the 77Br/133Xe clearance ratio. There was also a direct correlation between the 77Br/133Xe clearance ratio and the age of the patient in the diabetic group but not in the control group. 4. The results demonstrate that a reduced insulin response to oral glucose is associated with increased capillary permability and may play a role in the development of microangiopathy.", "contents": "Measurement of an index of muscle capillary permeability and its correlation with serum insulin values in maturity-onset diabetic subjects. 1. An index of capillary permeability was obtained by measuring the ratio of the clearance rate of 77Br to that of 133Xe in the anterior tibial muscle, after a short period of maximal ischaemic exercise. 2. Seventeen control subjects and thirty-two maturity-onset, non-insulin-treated diabetic subjects, aged 60 years or less, were studied. Short glucose tolerance tests were performed in the diabetic subjects during which blood sugar and serum insulin concentrations were estimated. 3. The 77Br/133Xe clearance ratio was increased in the diabetic subjects compared with the control subjects. In the diabetic subjects, there was an inverse correlation between the insulin at 60 min after glucose and the 77Br/133Xe clearance ratio. There was also a direct correlation between the 77Br/133Xe clearance ratio and the age of the patient in the diabetic group but not in the control group. 4. The results demonstrate that a reduced insulin response to oral glucose is associated with increased capillary permability and may play a role in the development of microangiopathy."} {"id": "PMID:1253526", "title": "Evidence for both luminal and systemic factors in the control of rat intestinal epithelial replacement.", "content": "1. Isolation of a self-emptying sac of rat small intestine in vivo halved the cell production rate in the crypts of Lieberk\u00fchn as measured by colchicine blockade. 2. Starvation for 48 h of rats with isolated intestinal sacs caused a further halving of cell production rate in the sac. 3. Infusion of distilled water into isolated intestinal sacs for 72 h caused a similar degree of stimulation of cell production in sacs in fed and starved rats, suggesting that the fall in cell production rate on starving a rat bearing an isolated sac is not due to t-e non-availability of the substances required for cell synthesis. 4. The possible contribution of innervation of the gut, and of systemic hormonal influences, on intestinal epithelial replacement is discussed.", "contents": "Evidence for both luminal and systemic factors in the control of rat intestinal epithelial replacement. 1. Isolation of a self-emptying sac of rat small intestine in vivo halved the cell production rate in the crypts of Lieberk\u00fchn as measured by colchicine blockade. 2. Starvation for 48 h of rats with isolated intestinal sacs caused a further halving of cell production rate in the sac. 3. Infusion of distilled water into isolated intestinal sacs for 72 h caused a similar degree of stimulation of cell production in sacs in fed and starved rats, suggesting that the fall in cell production rate on starving a rat bearing an isolated sac is not due to t-e non-availability of the substances required for cell synthesis. 4. The possible contribution of innervation of the gut, and of systemic hormonal influences, on intestinal epithelial replacement is discussed."} {"id": "PMID:1253527", "title": "The effect of chelating agents on cellular iron metabolism.", "content": "1. The effect of iron chelators on iron uptake, ferritin and total protein synthesis was studied in cultured Chang cells. Desferrioxamine depressed ferritin synthesis and completely inhibited iron uptake by ferritin protein. Rhodotorulic acid reduced iron uptake by the cells but had little effect on ferritin synthesis. Diethylenetriamine pentaacetic acid produced complete inhibition of iron uptake and all protein synthesis. 2,3-Dihydroxybenzoic acid (2,3-DHB) had no effect in this system. 2. When 2,3-DHB was incubated with a liver homogenate, its subsequent addition to a Chang cell culture resulted in depression of ferritin synthesis, iron uptake into the protein and some depression of total protein synthesis. Pretreatment of rhodotorulic acid did not affect its properties. 3. Non-ferritin iron in the Chang cell cytosol was dialysable, available for binding to transferrin and formed chelates which appeared, on gel chromatography, to be of low molecular weight. Gel chromatography of cytosol after incubation of the cells with chelating agents showed non-ferritin iron to be in a similar form. 4. Loss of non-ferritin iron from the cells occurred only when the transferrin in the medium was unsaturated. In the presence of chelating agents non-ferritin iron was lost from the cells even when transferrin was 100% saturated. 5. The results confirm the presence of an intracellular labile iron pool which is available for chelation, and demonstration that different iron chelators have different metabolic effects.", "contents": "The effect of chelating agents on cellular iron metabolism. 1. The effect of iron chelators on iron uptake, ferritin and total protein synthesis was studied in cultured Chang cells. Desferrioxamine depressed ferritin synthesis and completely inhibited iron uptake by ferritin protein. Rhodotorulic acid reduced iron uptake by the cells but had little effect on ferritin synthesis. Diethylenetriamine pentaacetic acid produced complete inhibition of iron uptake and all protein synthesis. 2,3-Dihydroxybenzoic acid (2,3-DHB) had no effect in this system. 2. When 2,3-DHB was incubated with a liver homogenate, its subsequent addition to a Chang cell culture resulted in depression of ferritin synthesis, iron uptake into the protein and some depression of total protein synthesis. Pretreatment of rhodotorulic acid did not affect its properties. 3. Non-ferritin iron in the Chang cell cytosol was dialysable, available for binding to transferrin and formed chelates which appeared, on gel chromatography, to be of low molecular weight. Gel chromatography of cytosol after incubation of the cells with chelating agents showed non-ferritin iron to be in a similar form. 4. Loss of non-ferritin iron from the cells occurred only when the transferrin in the medium was unsaturated. In the presence of chelating agents non-ferritin iron was lost from the cells even when transferrin was 100% saturated. 5. The results confirm the presence of an intracellular labile iron pool which is available for chelation, and demonstration that different iron chelators have different metabolic effects."} {"id": "PMID:1253528", "title": "Cell size and glucose oxidation rate in adipose tissue from non-diabetic and diabetic obese human subjects.", "content": "1. The rate of oxidation of [1-14C]glucose to 14CO2 was examined in subcutaneous adipose tissue from fifteen obese non-diabetic subjects and from eleven obese maturity-onset diabetic patients. Production of 14CO2, measured in the basal state and in the presence of insulin, was significantly correlated with mean cell size in both the non-diabetic and the diabetic subjects, independent of age, relative weight and fasting plasma insulin concentration. 2. Comparison of the regressions of glucose oxidation rates on mean cell size indicated: (i) that insulin produced a significant increase in activity over the basal value in both groups, and (ii) that basal and insulin-stimulated activity were both significantly lower in diabetic than in non-diabetic adipose tissue.", "contents": "Cell size and glucose oxidation rate in adipose tissue from non-diabetic and diabetic obese human subjects. 1. The rate of oxidation of [1-14C]glucose to 14CO2 was examined in subcutaneous adipose tissue from fifteen obese non-diabetic subjects and from eleven obese maturity-onset diabetic patients. Production of 14CO2, measured in the basal state and in the presence of insulin, was significantly correlated with mean cell size in both the non-diabetic and the diabetic subjects, independent of age, relative weight and fasting plasma insulin concentration. 2. Comparison of the regressions of glucose oxidation rates on mean cell size indicated: (i) that insulin produced a significant increase in activity over the basal value in both groups, and (ii) that basal and insulin-stimulated activity were both significantly lower in diabetic than in non-diabetic adipose tissue."} {"id": "PMID:1253529", "title": "Urinary excretion of hydroxylysyl glycosides during acute inflammation in the rat.", "content": "1. Subcutaneous inflammatory granuloma were induced in young rats and the urinary excretion of hydroxyproline and hydroxylysyl glycosides was observed during the period of acute inflammation. 2. All collagen metabolites were increased in the urine and excretion of glucosyl-galactosyl-hydroxylysine was much greater than excretion of galactosyl-hydroxylysine in the first days. 3. It is argued that urinary glucosyl-galactosyl-hydroxylysine is probably derived from hydroxylysyl residues of soluble collagen. 4. This study affords new arguments in favour of the dermal origin of urinary glucosyl-galactosyl-hydroxylysine, at least in skin inflammation.", "contents": "Urinary excretion of hydroxylysyl glycosides during acute inflammation in the rat. 1. Subcutaneous inflammatory granuloma were induced in young rats and the urinary excretion of hydroxyproline and hydroxylysyl glycosides was observed during the period of acute inflammation. 2. All collagen metabolites were increased in the urine and excretion of glucosyl-galactosyl-hydroxylysine was much greater than excretion of galactosyl-hydroxylysine in the first days. 3. It is argued that urinary glucosyl-galactosyl-hydroxylysine is probably derived from hydroxylysyl residues of soluble collagen. 4. This study affords new arguments in favour of the dermal origin of urinary glucosyl-galactosyl-hydroxylysine, at least in skin inflammation."} {"id": "PMID:1253530", "title": "Assessment of responsiveness to carbon dioxide in patients with chronic airways obstruction by rate of isometric inspiratory pressure development.", "content": "1. Responsiveness to CO2 was measured in forty patients with chronic airways obstruction in terms of ventilation and rate of isometric inspiratory pressure change [(dP/dt)max]. 2. The ventilatory response was below the normal range in eighteen out of twenty-two patients with normal arterial CO2 tensions and in all of eighteen patients with CO2 retention. 2. The (dP/dt)max. response was distributed throughout the normal range in all but one of the patients with normal arterial CO2 tension. In all the patients with CO2 retention the (dP/dt)max. response was either at or below the lower limit of the normal range. 4. Although the ventilatory responses correlated significantly with FEV1 there was no such correlation for the (dP/dt)max. responses. 5. The (dP/dt)max. response showed a significant negative correlation with Pa,CO2. 6. It is believed that the (dP/dt)max. response to CO2 can be used to assess central CO2 responsiveness in subjects with airways obstruction independently of mechanical factors limiting their ventilation.", "contents": "Assessment of responsiveness to carbon dioxide in patients with chronic airways obstruction by rate of isometric inspiratory pressure development. 1. Responsiveness to CO2 was measured in forty patients with chronic airways obstruction in terms of ventilation and rate of isometric inspiratory pressure change [(dP/dt)max]. 2. The ventilatory response was below the normal range in eighteen out of twenty-two patients with normal arterial CO2 tensions and in all of eighteen patients with CO2 retention. 2. The (dP/dt)max. response was distributed throughout the normal range in all but one of the patients with normal arterial CO2 tension. In all the patients with CO2 retention the (dP/dt)max. response was either at or below the lower limit of the normal range. 4. Although the ventilatory responses correlated significantly with FEV1 there was no such correlation for the (dP/dt)max. responses. 5. The (dP/dt)max. response showed a significant negative correlation with Pa,CO2. 6. It is believed that the (dP/dt)max. response to CO2 can be used to assess central CO2 responsiveness in subjects with airways obstruction independently of mechanical factors limiting their ventilation."} {"id": "PMID:1253531", "title": "Effect of nutritional status on rat adipose tissue, muscle and post-heparin plasma clearing factor lipase activities: their relationship to triglyceride fatty acid uptake by fat-cells and to plasma insulin concentrations.", "content": "1. In rats in a variety of nutritional states, the adipose tissue clearing factor lipase activity is strongly, positively correlated with fat-cell triglyceride fatty acid uptake. 2. In the same animals, muscle clearing factor lipase activity is inversely correlated with the activity of the enzyme in adipose tissue and with the plasma insulin concentration. 3. In starved animals that are given glucose, adipose tissue clearing factor lipase activity is positively correlated with the plasma insulin concentration. 4. The effect of changes in nutritional status on the activity of clearing factor lipase in rat post-heparin plasma depends on the heparin dosage used. The administration of glucose, but not of fructose or sucrose, to starved rats alters the response to heparin injection towards that found in rats in the fed state.", "contents": "Effect of nutritional status on rat adipose tissue, muscle and post-heparin plasma clearing factor lipase activities: their relationship to triglyceride fatty acid uptake by fat-cells and to plasma insulin concentrations. 1. In rats in a variety of nutritional states, the adipose tissue clearing factor lipase activity is strongly, positively correlated with fat-cell triglyceride fatty acid uptake. 2. In the same animals, muscle clearing factor lipase activity is inversely correlated with the activity of the enzyme in adipose tissue and with the plasma insulin concentration. 3. In starved animals that are given glucose, adipose tissue clearing factor lipase activity is positively correlated with the plasma insulin concentration. 4. The effect of changes in nutritional status on the activity of clearing factor lipase in rat post-heparin plasma depends on the heparin dosage used. The administration of glucose, but not of fructose or sucrose, to starved rats alters the response to heparin injection towards that found in rats in the fed state."} {"id": "PMID:1253532", "title": "The relation between the excretion of sodium and water and the perfusion pressure in the isolated, blood-perfused, rabbit kidney, with special reference to changes occurring in clip-hypertension.", "content": "1. The sodium and water excretion rates of rabbit kidneys were studied when isolated and perfused at known pressure with blood from another normal anaesthetized rabbit. Studies at several different perfusion pressures confirmed that a small rise in perfusion pressure caused a large rise in sodium excretion and that the potential sodium-excreting ability of the isolated kidney was high. The curve obtained could be closely fitted by a quadratic equation which allowed an estimate to be made of the blood pressure below which no urine is formed, i.e. the 'theoretical perfusion pressure threshold'. For normal kidneys this was 55-4 mmHg. 2. A group of rabbits had a silver clip applied to the left renal artery and, 3-6 weeks later, the eight most hypertensive animals were selected to provide their kidneys for perfusion. Both kidneys were perfused simultaneously. The clip on the left renal artery was removed immediately before perfusion and the cannula placed distal to the stenosis in the post-stenotic dilatation. The function curves of these kidneys were compared with the curves obtained from normal kidneys. 3. The untouched kidney contralateral to the clip was found to require a significantly higher perfusion pressure (71-7 mmHg) for it to achieve a given sodium excretion rate and, surprisingly, the clipped kidney showed a similar functional change (76-4 mmHg). In other words the positions of both function curves were shifted though their slopes were not much changed. 4. Both kidneys in single-clip-hypertension appear to adapt or reset their sodium excretory behaviour. The resetting in the untouched kidney allows hypertension to be sustained without undue sodium loss. Aldosterone probably contributes little to the resetting. We infer, indirectly, that the normal kidney may, to a significant extent, restrain sodium excretion by virtue of its sympathetic innervation. We also opine that the kidney cannot be assigned fixed intrinsic functional properties on which a renal sodium-handling theory of long-term blood pressure regulation can be firmly based.", "contents": "The relation between the excretion of sodium and water and the perfusion pressure in the isolated, blood-perfused, rabbit kidney, with special reference to changes occurring in clip-hypertension. 1. The sodium and water excretion rates of rabbit kidneys were studied when isolated and perfused at known pressure with blood from another normal anaesthetized rabbit. Studies at several different perfusion pressures confirmed that a small rise in perfusion pressure caused a large rise in sodium excretion and that the potential sodium-excreting ability of the isolated kidney was high. The curve obtained could be closely fitted by a quadratic equation which allowed an estimate to be made of the blood pressure below which no urine is formed, i.e. the 'theoretical perfusion pressure threshold'. For normal kidneys this was 55-4 mmHg. 2. A group of rabbits had a silver clip applied to the left renal artery and, 3-6 weeks later, the eight most hypertensive animals were selected to provide their kidneys for perfusion. Both kidneys were perfused simultaneously. The clip on the left renal artery was removed immediately before perfusion and the cannula placed distal to the stenosis in the post-stenotic dilatation. The function curves of these kidneys were compared with the curves obtained from normal kidneys. 3. The untouched kidney contralateral to the clip was found to require a significantly higher perfusion pressure (71-7 mmHg) for it to achieve a given sodium excretion rate and, surprisingly, the clipped kidney showed a similar functional change (76-4 mmHg). In other words the positions of both function curves were shifted though their slopes were not much changed. 4. Both kidneys in single-clip-hypertension appear to adapt or reset their sodium excretory behaviour. The resetting in the untouched kidney allows hypertension to be sustained without undue sodium loss. Aldosterone probably contributes little to the resetting. We infer, indirectly, that the normal kidney may, to a significant extent, restrain sodium excretion by virtue of its sympathetic innervation. We also opine that the kidney cannot be assigned fixed intrinsic functional properties on which a renal sodium-handling theory of long-term blood pressure regulation can be firmly based."} {"id": "PMID:1253533", "title": "A simple method of measuring breath hydrogen in carbohydrate malabsorption by end-expiratory sampling.", "content": "1. A simple method is described for measuring the hydrogen concentration in alveolar air by end-expiratory sampling, by using a modified Haldane-Priestley tube and gas chromatography. Hydrogen was generated in vivo by ingestion of the non-absorbable sugar lactulose. 2. Alveolar hydrogen concentration showed a highly significant correlation with hydrogen production measured either by a rebreathing technique or by a total collection procedure. 3. The coefficient of variation of the end-expiratory method, assessed by comparing sixty-one paired results, was 11-6%. The coefficient of variation in ten measurements in one subject at 1 min intervals was 17-6%.", "contents": "A simple method of measuring breath hydrogen in carbohydrate malabsorption by end-expiratory sampling. 1. A simple method is described for measuring the hydrogen concentration in alveolar air by end-expiratory sampling, by using a modified Haldane-Priestley tube and gas chromatography. Hydrogen was generated in vivo by ingestion of the non-absorbable sugar lactulose. 2. Alveolar hydrogen concentration showed a highly significant correlation with hydrogen production measured either by a rebreathing technique or by a total collection procedure. 3. The coefficient of variation of the end-expiratory method, assessed by comparing sixty-one paired results, was 11-6%. The coefficient of variation in ten measurements in one subject at 1 min intervals was 17-6%."} {"id": "PMID:1253540", "title": "The changing ecology of bacterial infections in children.", "content": "There is continued change in the organisms involved in commonly encountered infections. Although the major organisms have changed less in pediatric than in medical or surgical infections, the advances in neonatology and the chemotherapy of leukemia have resulted in cases in which infection with once uncommon organisms is now commonplace. Perhaps more disheartening has been the increasing resistance of bacteria to antibiotics. Since resistance patterns are so much a reflection of antibiotic usage patterns in an institution, each pediatrician must be aware of the species of bacteria and the resistance patterns of the bacteria isolated in his hospital, particularly in neonatal, intensive care, and burn areas where there is the highest use of antibiotics. Close interaction of pediatrician, diagnostic microbiology laboratory, and hospital epidemiologist can provide early clues to possible bacteria involved in infection, as well as suspected antibiotic resistance patterns.", "contents": "The changing ecology of bacterial infections in children. There is continued change in the organisms involved in commonly encountered infections. Although the major organisms have changed less in pediatric than in medical or surgical infections, the advances in neonatology and the chemotherapy of leukemia have resulted in cases in which infection with once uncommon organisms is now commonplace. Perhaps more disheartening has been the increasing resistance of bacteria to antibiotics. Since resistance patterns are so much a reflection of antibiotic usage patterns in an institution, each pediatrician must be aware of the species of bacteria and the resistance patterns of the bacteria isolated in his hospital, particularly in neonatal, intensive care, and burn areas where there is the highest use of antibiotics. Close interaction of pediatrician, diagnostic microbiology laboratory, and hospital epidemiologist can provide early clues to possible bacteria involved in infection, as well as suspected antibiotic resistance patterns."} {"id": "PMID:1253541", "title": "Peptic ulcer disease in children.", "content": "Physician recognition of peptic ulcers in children is a challenging problem because of the multiple, often nonspecific, symptoms. A compatible history and upper gastrointestinal contrast study were formerly all that was available to the practitioner trying to confirm his clinical impressions. With the advent of new developments in gastroduodenal endoscopy, lesions not detectable radiologically can be localized, and the diagnosis firmly established. As experience with this procedure in children accumulates, the incidence of other conditions previously attributed to ulcer disease may be apparent, thus enlarging our concepts of causes of upper gastrointestinal bleeding in children.", "contents": "Peptic ulcer disease in children. Physician recognition of peptic ulcers in children is a challenging problem because of the multiple, often nonspecific, symptoms. A compatible history and upper gastrointestinal contrast study were formerly all that was available to the practitioner trying to confirm his clinical impressions. With the advent of new developments in gastroduodenal endoscopy, lesions not detectable radiologically can be localized, and the diagnosis firmly established. As experience with this procedure in children accumulates, the incidence of other conditions previously attributed to ulcer disease may be apparent, thus enlarging our concepts of causes of upper gastrointestinal bleeding in children."} {"id": "PMID:1253550", "title": "Immunology of Allergy.", "content": "Immune reactions, presumably developed to rid organisms of troublesome invaders, are rather frequently associated with responses that result in injury to host tissue. Such responses are manifestations of allergy or hypersensitivity, and involve antibodies of certain immunoglobulin classes, complement components, mast cells and basophils, lymphocytes, macrophages, and various pharmacologic mediators and other soluble substances in an exuberant array of possible combinations. An understanding of clinical hypersensitivity diseases is aided by classifying basic allergic mechanisms into four main types: anaphylactic (Type I), cytotoxic (Type II), complex-mediated (Type III), and cell-mediated (Type IV), which may participate in various combinations in disease states.", "contents": "Immunology of Allergy. Immune reactions, presumably developed to rid organisms of troublesome invaders, are rather frequently associated with responses that result in injury to host tissue. Such responses are manifestations of allergy or hypersensitivity, and involve antibodies of certain immunoglobulin classes, complement components, mast cells and basophils, lymphocytes, macrophages, and various pharmacologic mediators and other soluble substances in an exuberant array of possible combinations. An understanding of clinical hypersensitivity diseases is aided by classifying basic allergic mechanisms into four main types: anaphylactic (Type I), cytotoxic (Type II), complex-mediated (Type III), and cell-mediated (Type IV), which may participate in various combinations in disease states."} {"id": "PMID:1253604", "title": "Serologic evidence of equine leptospirosis in the northeast United States.", "content": "Serologic testing for leptospiral antibody was conducted with the macroscopic agglutination test on 1,346 equine serum samples. These were collected from clinically normal horses in 123 purebred herds in the Northeast. Sixty-eight samples (5%) from the population tested reacted at significant levels (1:40 or higher) to one or more of the 5 serotype antigens used. These reactors were from 38 (31%) of the herds tested. Reactions to serotype pomona predominated in 25 (72%) of these 38 herds. Smaller numbers of herds had reactors to canicola, icterohemorrhagiae and grippotyphosa. No significant reactions to serotype hardjo were detected.", "contents": "Serologic evidence of equine leptospirosis in the northeast United States. Serologic testing for leptospiral antibody was conducted with the macroscopic agglutination test on 1,346 equine serum samples. These were collected from clinically normal horses in 123 purebred herds in the Northeast. Sixty-eight samples (5%) from the population tested reacted at significant levels (1:40 or higher) to one or more of the 5 serotype antigens used. These reactors were from 38 (31%) of the herds tested. Reactions to serotype pomona predominated in 25 (72%) of these 38 herds. Smaller numbers of herds had reactors to canicola, icterohemorrhagiae and grippotyphosa. No significant reactions to serotype hardjo were detected."} {"id": "PMID:1253605", "title": "A rheumatoid-like arthritis in calves.", "content": "Arthritis characterized by lameness. Joint swelling and purulent synovial fluid was seen in a group of dairy replacement heifers. Mycoplasma was cultured from one joint aspirate, but all bacterial cultures were negative. Antiglobulins were demonstrated by double diffusion precipitin tests in the serum and synovial fluid. Due to the clinical and clinical pathological similarities to rheumatoid arthritis in man, the disease was called rheumatoid-like arthritis. The presence of antiglobulin may indicate antibody in the synovial fluid explaining the difficulty in culturing a causative agent.", "contents": "A rheumatoid-like arthritis in calves. Arthritis characterized by lameness. Joint swelling and purulent synovial fluid was seen in a group of dairy replacement heifers. Mycoplasma was cultured from one joint aspirate, but all bacterial cultures were negative. Antiglobulins were demonstrated by double diffusion precipitin tests in the serum and synovial fluid. Due to the clinical and clinical pathological similarities to rheumatoid arthritis in man, the disease was called rheumatoid-like arthritis. The presence of antiglobulin may indicate antibody in the synovial fluid explaining the difficulty in culturing a causative agent."} {"id": "PMID:1253608", "title": "The pathology of subacute methylmerculialism in swine.", "content": "Clinical signs of toxicosis, neurologic lesions, and elevated tissue residues of methylmercury (MM) were produced in 12 pigs by oral administration of 1.29, 0.86, 0.64, and 0.43 mg mercury/kg of body weight daily as methylmercuric hydroxide (MMH). Clinical signs which began on day 17 were ataxia, dysmetria, blindness, convulsions, paresis, and death. Time of onset of signs was inversely related to size of daily dose. Microscopic lesions were found in the cerebrum brain stem, and spinal cord, and correlated well with clinical signs. The cerebrum in which severity of lesions was directly related to length of exposure was the most severely affected region of the central nervous system (CNS). Lesions were neuronal necrosis, neuronophagia, cortical vacuolation, axon swelling, gliosis, leptomeningitis, and vascular fibrinoid necrosis. Neuronal necrosis was most extensive within mid and deep cerebrocortical laminae. Brain residues of MM were directly proportional to the size of daily dose, and statistically significant. Distribution of MM among different tissues was rather uniform with highest concentrations found in liver, followed by kidney, muscle, spleen, and brain.", "contents": "The pathology of subacute methylmerculialism in swine. Clinical signs of toxicosis, neurologic lesions, and elevated tissue residues of methylmercury (MM) were produced in 12 pigs by oral administration of 1.29, 0.86, 0.64, and 0.43 mg mercury/kg of body weight daily as methylmercuric hydroxide (MMH). Clinical signs which began on day 17 were ataxia, dysmetria, blindness, convulsions, paresis, and death. Time of onset of signs was inversely related to size of daily dose. Microscopic lesions were found in the cerebrum brain stem, and spinal cord, and correlated well with clinical signs. The cerebrum in which severity of lesions was directly related to length of exposure was the most severely affected region of the central nervous system (CNS). Lesions were neuronal necrosis, neuronophagia, cortical vacuolation, axon swelling, gliosis, leptomeningitis, and vascular fibrinoid necrosis. Neuronal necrosis was most extensive within mid and deep cerebrocortical laminae. Brain residues of MM were directly proportional to the size of daily dose, and statistically significant. Distribution of MM among different tissues was rather uniform with highest concentrations found in liver, followed by kidney, muscle, spleen, and brain."} {"id": "PMID:1253609", "title": "Naturally occurring cerebrospinal parelaphostronglylosis.", "content": "An isolated case and an outbreak of parelaphostrongylosis in goats are described. Signs included tetraparesis, hemiparesis, tetraplegia, spastic gait, scoliosis, vestibular strabismus, blindness, and death. Five cases were necropsied and nematodes were seen in the brain and spinal cord of four of these. Intact adult nematodes from two cases were identified as Parelaphostrongylus tenuis, the meningeal worm of white-tailed deer. Cerebrospinal fluid analysis from affected goats showed a moderately elevated protein content, evidence of hemorrhage, and mononuclear cell and eosinophil pleocytosis. Recoveries are recorded.", "contents": "Naturally occurring cerebrospinal parelaphostronglylosis. An isolated case and an outbreak of parelaphostrongylosis in goats are described. Signs included tetraparesis, hemiparesis, tetraplegia, spastic gait, scoliosis, vestibular strabismus, blindness, and death. Five cases were necropsied and nematodes were seen in the brain and spinal cord of four of these. Intact adult nematodes from two cases were identified as Parelaphostrongylus tenuis, the meningeal worm of white-tailed deer. Cerebrospinal fluid analysis from affected goats showed a moderately elevated protein content, evidence of hemorrhage, and mononuclear cell and eosinophil pleocytosis. Recoveries are recorded."} {"id": "PMID:1253610", "title": "A malignant neoplasm resembling a circumanal gland adenocarcinoma in a dog.", "content": "In the neoplasm of this report a final diagnosis of a circumanal gland adenocarcinoma invading the vertebral column and canal was made based on the histologic appearance. No growths were noted in the circumanal gland region and the location of the primary neoplasm is open to debate.", "contents": "A malignant neoplasm resembling a circumanal gland adenocarcinoma in a dog. In the neoplasm of this report a final diagnosis of a circumanal gland adenocarcinoma invading the vertebral column and canal was made based on the histologic appearance. No growths were noted in the circumanal gland region and the location of the primary neoplasm is open to debate."} {"id": "PMID:1253626", "title": "Adjustment of cephaloridine (Keflodin): dosage according to its pharmacokinetics.", "content": "The determination of the serum and urine concentrations of cephaloridine permitted calculation of the pharmacokinetic constants of this antibiotic: after administration of a 1-gram intravenous dose in five normal subjects; after administration of a 1-gram intramuscular dose in five normal subjects, five patients with renal impairment and five patients on maintenance hemodialysis. In normal subjects, serum half-life averaged 1.56 h (Ke=0.4445) after intravenous administration and 1.63 h (Ke=0.4254) after intramuscular administration of a 1-gram dose of the antibiotic. The urinary excretion of cephaloridine over the 6 h following its intramuscular administration in normal subjects amounted to 56.4% of the administered dose. The renal clearance of cephaloridine was 194 ml/min. A linear correlation (Ke=0.0670+0.0028 CrCl) was established between overall elimination rate-constant values and the creatinine clearances of the patients under investigation. These data were used to calculate the maintenance and loading doses and intervals adjusted to creatinine clearance values. Accurate dosage regimens adjusted to the renal status of each individual patient were derived from the calculated values.", "contents": "Adjustment of cephaloridine (Keflodin): dosage according to its pharmacokinetics. The determination of the serum and urine concentrations of cephaloridine permitted calculation of the pharmacokinetic constants of this antibiotic: after administration of a 1-gram intravenous dose in five normal subjects; after administration of a 1-gram intramuscular dose in five normal subjects, five patients with renal impairment and five patients on maintenance hemodialysis. In normal subjects, serum half-life averaged 1.56 h (Ke=0.4445) after intravenous administration and 1.63 h (Ke=0.4254) after intramuscular administration of a 1-gram dose of the antibiotic. The urinary excretion of cephaloridine over the 6 h following its intramuscular administration in normal subjects amounted to 56.4% of the administered dose. The renal clearance of cephaloridine was 194 ml/min. A linear correlation (Ke=0.0670+0.0028 CrCl) was established between overall elimination rate-constant values and the creatinine clearances of the patients under investigation. These data were used to calculate the maintenance and loading doses and intervals adjusted to creatinine clearance values. Accurate dosage regimens adjusted to the renal status of each individual patient were derived from the calculated values."} {"id": "PMID:1253627", "title": "Comparative pharmacokinetic studies of ornidazole and metronidazole in man.", "content": "Pharmacokinetic characteristics of ornidazole and metronidazole were compared in man. Both drugs were labelled with 14C in the imidazole ring at position 2. Four healthy volunteers were given an oral dose of 750 mg of one of the drugs, followed 2--4 weeks later by the same dose of the other. The same technique for determining the unchanged compound was used for both drugs. Results may be summarized as follows: mean peak concentrations in the plasma of 10.9 mug/ml for ornidazole and of 12.3 mug/ml for metronidazole were reached 2--4 h and 30--60 min after administration, respectively; both drugs showed the same volume of distribution. Their binding to human plasma proteins was less than 15%; the mean half-life of elimination from the plasma was 14.4 h for ornidazole and 8.4 h for metronidazole; the mean radioactivity recovered from the urine and faeces during the first 5 days was 85% of the dose for ornidazole and 91% for metronidazole, the major proportion in each case being excreted in the urine; the radioactivity found in the faeces was 22.1% of the dose for ornidazole and 13.9% for metronidazole.", "contents": "Comparative pharmacokinetic studies of ornidazole and metronidazole in man. Pharmacokinetic characteristics of ornidazole and metronidazole were compared in man. Both drugs were labelled with 14C in the imidazole ring at position 2. Four healthy volunteers were given an oral dose of 750 mg of one of the drugs, followed 2--4 weeks later by the same dose of the other. The same technique for determining the unchanged compound was used for both drugs. Results may be summarized as follows: mean peak concentrations in the plasma of 10.9 mug/ml for ornidazole and of 12.3 mug/ml for metronidazole were reached 2--4 h and 30--60 min after administration, respectively; both drugs showed the same volume of distribution. Their binding to human plasma proteins was less than 15%; the mean half-life of elimination from the plasma was 14.4 h for ornidazole and 8.4 h for metronidazole; the mean radioactivity recovered from the urine and faeces during the first 5 days was 85% of the dose for ornidazole and 91% for metronidazole, the major proportion in each case being excreted in the urine; the radioactivity found in the faeces was 22.1% of the dose for ornidazole and 13.9% for metronidazole."} {"id": "PMID:1253628", "title": "Characteristics of biliary excretion of cefazolin and other cephalosporins with reference to the relationship between serum levels and administration conditions.", "content": "The biliary excretion of cefazolin was compared with that of cephalothin and cephaloridine in rats and man. In rats, the biliary levels were dose-related with cefazolin and cephalothin but not with cephaloridine. Biliary levels were higher than serum levels after injection of 10--80 mg/kg of cefazolin and cephalothin, whereas serum levels of cephaloridine after injection were higher than biliary levels. The highest biliary levels of cefazolin were obtained by intravenous injection, followed by intramuscular injection and drip infusion. In man, a crossover study was made to compare biliary levels of cefazolin with those of cephaloridine and cephalothin. After a single 1-gram intravenous injection, the peak levels of cefazolin ranged from 0.85 to 21 mug/ml and those of cephaloridine varied from 0.55 to 3.9 mug/ml. After a 3-gram intravenous injection, the peak biliary levels of cefazolin ranged from 35.5 to 270 mug/ml and those of cephalothin from 0.3 to 64 mug/ml. The chemotherapeutic biliary levels of cefazolin able to inhibit susceptible organisms were obtained by 3-gram intravenous injections.", "contents": "Characteristics of biliary excretion of cefazolin and other cephalosporins with reference to the relationship between serum levels and administration conditions. The biliary excretion of cefazolin was compared with that of cephalothin and cephaloridine in rats and man. In rats, the biliary levels were dose-related with cefazolin and cephalothin but not with cephaloridine. Biliary levels were higher than serum levels after injection of 10--80 mg/kg of cefazolin and cephalothin, whereas serum levels of cephaloridine after injection were higher than biliary levels. The highest biliary levels of cefazolin were obtained by intravenous injection, followed by intramuscular injection and drip infusion. In man, a crossover study was made to compare biliary levels of cefazolin with those of cephaloridine and cephalothin. After a single 1-gram intravenous injection, the peak levels of cefazolin ranged from 0.85 to 21 mug/ml and those of cephaloridine varied from 0.55 to 3.9 mug/ml. After a 3-gram intravenous injection, the peak biliary levels of cefazolin ranged from 35.5 to 270 mug/ml and those of cephalothin from 0.3 to 64 mug/ml. The chemotherapeutic biliary levels of cefazolin able to inhibit susceptible organisms were obtained by 3-gram intravenous injections."} {"id": "PMID:1253629", "title": "Sulphamethoxazole-trimethoprim: effect on antibody response in man.", "content": "The possible immunosuppressive properties of the combination sulphamethoxazole-trimethoprim or either of the agents alone were studied in healthy human volunteers. The effect of the 4-day drug treatment on the antibody synthesis after vaccination was measured by titrating tetanus antitoxin, mumps antibody and Salmonella Hb antibody levels 4 and 5 weeks after vaccination. No significant differences were found in mumps or Salmonella antibody titres in the drug-treated group compared to controls. Tetanus antitoxin levels, however, were significantly lower than in controls after the combined drug. When a fourfold or greater increase in tetanus antitoxin titre was obtained in 75% of controls, the respective figures were 38% in the sulphamethoxazole-trimethoprim-treated group (p less than 0.05), 45% in the trimethoprim group (p greater than 0.05), and 50% in the sulphamethoxazole group (p greater than 0.05). The implications of these findings are discussed.", "contents": "Sulphamethoxazole-trimethoprim: effect on antibody response in man. The possible immunosuppressive properties of the combination sulphamethoxazole-trimethoprim or either of the agents alone were studied in healthy human volunteers. The effect of the 4-day drug treatment on the antibody synthesis after vaccination was measured by titrating tetanus antitoxin, mumps antibody and Salmonella Hb antibody levels 4 and 5 weeks after vaccination. No significant differences were found in mumps or Salmonella antibody titres in the drug-treated group compared to controls. Tetanus antitoxin levels, however, were significantly lower than in controls after the combined drug. When a fourfold or greater increase in tetanus antitoxin titre was obtained in 75% of controls, the respective figures were 38% in the sulphamethoxazole-trimethoprim-treated group (p less than 0.05), 45% in the trimethoprim group (p greater than 0.05), and 50% in the sulphamethoxazole group (p greater than 0.05). The implications of these findings are discussed."} {"id": "PMID:1253630", "title": "The effect of erythromycin on the growth of Rickettsia prowazekii in the body louse (Pediculus humanus corporis L) and the tick (Ornithodoros moubata Murray).", "content": "Body lice (Pediculus humanus corporis L) and ticks (Ornithodoros moubata) that had been infected with Rickettsia prowazekii received varying doses of erythromycin. The anti-rickettsial activity of this drug was evaluated with regard to the determination of the numbers of surviving microorganism (LID100) and the in vivo concentration of erythromycin in both arthropod hosts. Erythromycin was found to exert a rickettsiostatic effect in lice, whereas in ticks the drug at concentrations of 0.3--0.04 mug/mg body weight completely eliminated R. prowazekii.", "contents": "The effect of erythromycin on the growth of Rickettsia prowazekii in the body louse (Pediculus humanus corporis L) and the tick (Ornithodoros moubata Murray). Body lice (Pediculus humanus corporis L) and ticks (Ornithodoros moubata) that had been infected with Rickettsia prowazekii received varying doses of erythromycin. The anti-rickettsial activity of this drug was evaluated with regard to the determination of the numbers of surviving microorganism (LID100) and the in vivo concentration of erythromycin in both arthropod hosts. Erythromycin was found to exert a rickettsiostatic effect in lice, whereas in ticks the drug at concentrations of 0.3--0.04 mug/mg body weight completely eliminated R. prowazekii."} {"id": "PMID:1253632", "title": "Fosfomycin in Osteomyelitis.", "content": "Fosfomycin was exclusively used as antibiotic treatment in 37 patients suffering from osteomyelitis, out ot which 23 were operated for sequestrectomy or fistulectomy, whereas the remaining 14 did not undergo any surgery during fosfomycin treatment. Fosfomycin was adminsitered parenterally, alone or combined with oral administration, and in some cases only orally. The dosage varied from 4 to 8 g/day for an average period of 3 weeks. After one or two treatments the results were 29 definitive cures (78%), 2 failures and 6 relapses (22%).", "contents": "Fosfomycin in Osteomyelitis. Fosfomycin was exclusively used as antibiotic treatment in 37 patients suffering from osteomyelitis, out ot which 23 were operated for sequestrectomy or fistulectomy, whereas the remaining 14 did not undergo any surgery during fosfomycin treatment. Fosfomycin was adminsitered parenterally, alone or combined with oral administration, and in some cases only orally. The dosage varied from 4 to 8 g/day for an average period of 3 weeks. After one or two treatments the results were 29 definitive cures (78%), 2 failures and 6 relapses (22%)."} {"id": "PMID:1253633", "title": "Comparative assessment of cylacillin and ampicillin by experimental therapy and by serum level determinations in rats and mice.", "content": "Therapy of chronic E. coli pyelonephritis in rats was equally effective with cyclacillin and oral ampicillin, whereas intramuscular ampicillin had a significantly higher therapeutic activity than oral cyclacillin. Serum concentrations in rats and mice were consistently higher with cyclacillin than with ampicillin and showed great variations depending on the animal species. It was concluded that there is a good correlation between in vivo and in vitro activity of both antibiotics, provided that the serum levels are taken into consideration. On this basis it may be predicted that a man cyclacillin will exhibit lower therapeutic activity in gram-negative infections than ampicillin.", "contents": "Comparative assessment of cylacillin and ampicillin by experimental therapy and by serum level determinations in rats and mice. Therapy of chronic E. coli pyelonephritis in rats was equally effective with cyclacillin and oral ampicillin, whereas intramuscular ampicillin had a significantly higher therapeutic activity than oral cyclacillin. Serum concentrations in rats and mice were consistently higher with cyclacillin than with ampicillin and showed great variations depending on the animal species. It was concluded that there is a good correlation between in vivo and in vitro activity of both antibiotics, provided that the serum levels are taken into consideration. On this basis it may be predicted that a man cyclacillin will exhibit lower therapeutic activity in gram-negative infections than ampicillin."} {"id": "PMID:1253634", "title": "The simultaneous quantitative determination of total, 'active', acetylated and conjugated sulfonamide in biological fluids.", "content": "Methods are proposed which, in combination with those described in an earlier publication by the author, enable the separate determination of the two main types of sulfonamide metabolites, the N4-acetyl derivative and the conjugates, besides the total and the active sulfonamide in body fluids.", "contents": "The simultaneous quantitative determination of total, 'active', acetylated and conjugated sulfonamide in biological fluids. Methods are proposed which, in combination with those described in an earlier publication by the author, enable the separate determination of the two main types of sulfonamide metabolites, the N4-acetyl derivative and the conjugates, besides the total and the active sulfonamide in body fluids."} {"id": "PMID:1253635", "title": "Conversion of benzylpenicillin to penicilloic acid in patients with chronic bronchial infections.", "content": "A colorimetric method was modified to estimate the levels of benzylpenicillin and its penicilloic acid in urine. When benzylpenicillin was given orally to healthy volunteers, both it and its penicilloic acid were detected in the urine. When benzylpenicillin was given by intramuscular injections to these volunteers, only benzylpenicillin was detected in the urine. Patients suffering from chronic bronchial infections that exhibited beta-lactamase producing gram-negative bacteria in their sputum were given benzylpenicillin intramuscularly. It was found that both benzylpenicillin and penicilloic acid were recovered from the urine of such patients.", "contents": "Conversion of benzylpenicillin to penicilloic acid in patients with chronic bronchial infections. A colorimetric method was modified to estimate the levels of benzylpenicillin and its penicilloic acid in urine. When benzylpenicillin was given orally to healthy volunteers, both it and its penicilloic acid were detected in the urine. When benzylpenicillin was given by intramuscular injections to these volunteers, only benzylpenicillin was detected in the urine. Patients suffering from chronic bronchial infections that exhibited beta-lactamase producing gram-negative bacteria in their sputum were given benzylpenicillin intramuscularly. It was found that both benzylpenicillin and penicilloic acid were recovered from the urine of such patients."} {"id": "PMID:1253636", "title": "Effect of trimethoprim on the occurrence of drug-resistant coliform bacteria in the faecal flora.", "content": "The occurrence of drug-resistant coliform bacteria was studied in the faecal flora of 30 persons receiving for 3 weeks either trimethoprim alone, a combination of sulphamethoxazole and trimethoprim, or a combination of sulphamethoxydiazine and sulphamethoxazole. Bacterial sensitivity was tested against trimethoprim, sulphamethoxazole-trimethoprim, sulphamethoxazole, and sulphaisodimidine. After treatment with trimethoprim alone, no increase in the occurrence of strains resistant to either trimethoprim or sulphonamides was observed. After treatment with sulphamethoxazole-trimethoprim, the faecal flora contained an increased percentage of sulphonamide-resistant coliforms but significantly less than found after treatment with sulphamethoxydiazine-sulphamethoxazole. In the persons receiving the sulphonamides only, a rapid increase in sulphonamide-resistant coliforms was observed. During the whole study, only one trimethoprim-resistant coliform strain was detected.", "contents": "Effect of trimethoprim on the occurrence of drug-resistant coliform bacteria in the faecal flora. The occurrence of drug-resistant coliform bacteria was studied in the faecal flora of 30 persons receiving for 3 weeks either trimethoprim alone, a combination of sulphamethoxazole and trimethoprim, or a combination of sulphamethoxydiazine and sulphamethoxazole. Bacterial sensitivity was tested against trimethoprim, sulphamethoxazole-trimethoprim, sulphamethoxazole, and sulphaisodimidine. After treatment with trimethoprim alone, no increase in the occurrence of strains resistant to either trimethoprim or sulphonamides was observed. After treatment with sulphamethoxazole-trimethoprim, the faecal flora contained an increased percentage of sulphonamide-resistant coliforms but significantly less than found after treatment with sulphamethoxydiazine-sulphamethoxazole. In the persons receiving the sulphonamides only, a rapid increase in sulphonamide-resistant coliforms was observed. During the whole study, only one trimethoprim-resistant coliform strain was detected."} {"id": "PMID:1253641", "title": "Myths and mechanisms of meiosis.", "content": "A comparative analysis of the meiotic secquence in a wide variety of organisms indicates there is no convincing evidence that: (1) Premeiotic pairing plays any role in the synapsis of homologues. (2) Heterochromatic association facilitates homologous pairing. (3) Chiasmata ever form within segments which are positively heteropycnotic at zygotenepachytene. (4) Localisation of chiasmata depends on prior localisation of pairing or on the occurrence of euchromatin-heterochromatin boundaries. (5) Prior association of centromeres plays any role in determing co-orientation. (6) Any form of supra-chromosomal organisation exists involving permanent association between the members of a haploid complement, and (7) Unequal progeny ratios recovered from structurally modified Drosophila complements arise as a consequence of distributive pairing.--On the other hand there is good evidence that: (1) Interlocking of bivalents can occur regularly in species with a chiasma frequency sufficiently high to regularly produce ring bivalents and in which the chiasmata are localised to the ends of the bivalent. (2) Some forms of terminal association cannot represent terminalised chiasmata. (3) U-type exchanges present at diplotene result from errors in crossing over. (4) Pairing and chiasma formation are not necessary for coorientation, and (5) at least some types of elastic constrictions present at first metaphase represent extended nucleolar organisers.", "contents": "Myths and mechanisms of meiosis. A comparative analysis of the meiotic secquence in a wide variety of organisms indicates there is no convincing evidence that: (1) Premeiotic pairing plays any role in the synapsis of homologues. (2) Heterochromatic association facilitates homologous pairing. (3) Chiasmata ever form within segments which are positively heteropycnotic at zygotenepachytene. (4) Localisation of chiasmata depends on prior localisation of pairing or on the occurrence of euchromatin-heterochromatin boundaries. (5) Prior association of centromeres plays any role in determing co-orientation. (6) Any form of supra-chromosomal organisation exists involving permanent association between the members of a haploid complement, and (7) Unequal progeny ratios recovered from structurally modified Drosophila complements arise as a consequence of distributive pairing.--On the other hand there is good evidence that: (1) Interlocking of bivalents can occur regularly in species with a chiasma frequency sufficiently high to regularly produce ring bivalents and in which the chiasmata are localised to the ends of the bivalent. (2) Some forms of terminal association cannot represent terminalised chiasmata. (3) U-type exchanges present at diplotene result from errors in crossing over. (4) Pairing and chiasma formation are not necessary for coorientation, and (5) at least some types of elastic constrictions present at first metaphase represent extended nucleolar organisers."} {"id": "PMID:1253642", "title": "The in situ formation of DNA-DNA duplexes of drosophila virilis satellite DNA.", "content": "The DNA of Drosophila virilis brains and imaginal discs was labeled in vitro to a specific activity of 6 X 10(-5) dpm/mug, using an organ culture medium. The DNA was fractionated on neutral and alkaline CsC1 gradients and the heavy strands of satellite I annealed in situ to denatured polytene chromosomes from squash preparations of larval salivary glands. Nuclease S1 from Aspergillus oryzae was used to digest the unpaired ssDNA, resulting in a distinct labeling of the alpha-heterochromatin in the chromocenter and a small amount of diffused labeling in the proximal beta-heterochromatic part of the X-Chromsome.", "contents": "The in situ formation of DNA-DNA duplexes of drosophila virilis satellite DNA. The DNA of Drosophila virilis brains and imaginal discs was labeled in vitro to a specific activity of 6 X 10(-5) dpm/mug, using an organ culture medium. The DNA was fractionated on neutral and alkaline CsC1 gradients and the heavy strands of satellite I annealed in situ to denatured polytene chromosomes from squash preparations of larval salivary glands. Nuclease S1 from Aspergillus oryzae was used to digest the unpaired ssDNA, resulting in a distinct labeling of the alpha-heterochromatin in the chromocenter and a small amount of diffused labeling in the proximal beta-heterochromatic part of the X-Chromsome."} {"id": "PMID:1253643", "title": "Light and electron microscopy of rat kangaroo cells in mitosis. III. Patterns of chromosome behavior during prometaphase.", "content": "Chromosome orientation and behavior during prometaphase of mitosis in PtK1 rat kangaroo cells were investigated by cin\u00e9micrography and electron microscopy. The first chromosome movements occur soon after the nuclear envelope begins to break down in the region near each pole. Initial chromosome behavior is primarily determined by the distance from the kinetochore region to the spindle poles. The predominant pattern is a movement to and/or association with the proximal pole. Movement to and association with the more distant pole, or direct alignment at or near the spindle equator (direct congression) are less frequent patterns. Except for rare cases, pole-associated chromosomes congress sooner or later and most congressed chromosomes oscillate about the equator.--Ultrastructural observations suggest that pole-associated chromosomes are oriented only to the poximal pole (monotelic or syntelic orientation) and they demonstrate that the sister-kinetochores of congressing or oscillating chromosomes are oriented to opposite poles (amphitelic orientation).--Based on the structure of the early prometaphase spindle and four assumptions concerning the formation of kinetochore fibers and their force-producing interaction with complementary elements, the different patterns of chromosome behavior observed can be explained as a result of synchronous or asynchronous formation of sister-kinetochore fibers. The few chromosomes whose kinetochore region is approximately equidistant from the poles amphi-orient immediately because their sister-kinetochores form fibers synchronously and they congress directly because of the bidirectional forces to which they are subjected. The kinetochore region of most chromosomes is not equidistant from the poles. Therefore, they form a functional fiber first to the nearer pole and move to, or associate with it, it because of the unidirectional force. Eventually, however, these chromosomes achieve amphitelic orientation and congress. Once established, amphitelic orientation is stable. Re-orientations do not occur during congression or oscillatory movements.", "contents": "Light and electron microscopy of rat kangaroo cells in mitosis. III. Patterns of chromosome behavior during prometaphase. Chromosome orientation and behavior during prometaphase of mitosis in PtK1 rat kangaroo cells were investigated by cin\u00e9micrography and electron microscopy. The first chromosome movements occur soon after the nuclear envelope begins to break down in the region near each pole. Initial chromosome behavior is primarily determined by the distance from the kinetochore region to the spindle poles. The predominant pattern is a movement to and/or association with the proximal pole. Movement to and association with the more distant pole, or direct alignment at or near the spindle equator (direct congression) are less frequent patterns. Except for rare cases, pole-associated chromosomes congress sooner or later and most congressed chromosomes oscillate about the equator.--Ultrastructural observations suggest that pole-associated chromosomes are oriented only to the poximal pole (monotelic or syntelic orientation) and they demonstrate that the sister-kinetochores of congressing or oscillating chromosomes are oriented to opposite poles (amphitelic orientation).--Based on the structure of the early prometaphase spindle and four assumptions concerning the formation of kinetochore fibers and their force-producing interaction with complementary elements, the different patterns of chromosome behavior observed can be explained as a result of synchronous or asynchronous formation of sister-kinetochore fibers. The few chromosomes whose kinetochore region is approximately equidistant from the poles amphi-orient immediately because their sister-kinetochores form fibers synchronously and they congress directly because of the bidirectional forces to which they are subjected. The kinetochore region of most chromosomes is not equidistant from the poles. Therefore, they form a functional fiber first to the nearer pole and move to, or associate with it, it because of the unidirectional force. Eventually, however, these chromosomes achieve amphitelic orientation and congress. Once established, amphitelic orientation is stable. Re-orientations do not occur during congression or oscillatory movements."} {"id": "PMID:1253644", "title": "Centriole behavior in early mitosis of rat kangaroo cells (PTK2).", "content": "Behavior of the centriolar duplexes during early mitosis was investigated. In general, both duplexes are capable of migrating about the cell as a unit with little change in their center to center spacing prior to separation to form the spindle poles. This duplex separation may occur at any point within the mid-prophase-prometaphase period. If it is delayed to prometaphase, transitory monopolar spindles were observed.", "contents": "Centriole behavior in early mitosis of rat kangaroo cells (PTK2). Behavior of the centriolar duplexes during early mitosis was investigated. In general, both duplexes are capable of migrating about the cell as a unit with little change in their center to center spacing prior to separation to form the spindle poles. This duplex separation may occur at any point within the mid-prophase-prometaphase period. If it is delayed to prometaphase, transitory monopolar spindles were observed."} {"id": "PMID:1253645", "title": "Effects of treatment on differential staining of BrdU labeled metaphase chromosomes: three-way differentiation of M3 chromosomes.", "content": "In this paper methodology is described which yields three-way Giemsa differentiation (light-medium-dark) in human metaphase chromosomes exposed to 5-bromodeoxyuridine (BrdU) for 3 DNA synthetic periods (or exposed for 2 DNA synthetic periods and removed from exposure for the third) by means of which all of the sister chromatid exchanges (SCEs) occurring during (or shortly after) S1, S2 and S3 can be accurately counted and distinguished from one another. Using these methods it has been demonstrated that approximately twice as many SCEs occur during the first S-period in the presence of the drug (labeling=B1T0XT0B1)1 as occur during the second S-period (labeling=B2B1XT0B2)1. The three-way differentiation pattern is thought to result from a stepwise decrease in the amount of BrdU incorporated during the first, second and third DNA synthetic periods. These methods can also be used to differentiate between unlabeled (T2T0) and unifilarly labeled (B1T2) sister chromatids and are potentially useful in the detection of sub-chromatid exchanges (none were detected).", "contents": "Effects of treatment on differential staining of BrdU labeled metaphase chromosomes: three-way differentiation of M3 chromosomes. In this paper methodology is described which yields three-way Giemsa differentiation (light-medium-dark) in human metaphase chromosomes exposed to 5-bromodeoxyuridine (BrdU) for 3 DNA synthetic periods (or exposed for 2 DNA synthetic periods and removed from exposure for the third) by means of which all of the sister chromatid exchanges (SCEs) occurring during (or shortly after) S1, S2 and S3 can be accurately counted and distinguished from one another. Using these methods it has been demonstrated that approximately twice as many SCEs occur during the first S-period in the presence of the drug (labeling=B1T0XT0B1)1 as occur during the second S-period (labeling=B2B1XT0B2)1. The three-way differentiation pattern is thought to result from a stepwise decrease in the amount of BrdU incorporated during the first, second and third DNA synthetic periods. These methods can also be used to differentiate between unlabeled (T2T0) and unifilarly labeled (B1T2) sister chromatids and are potentially useful in the detection of sub-chromatid exchanges (none were detected)."} {"id": "PMID:1253646", "title": "Karotype, DNA replication and origin of sex chromosomes in Anopheles atroparvus.", "content": "Anopheles atroparvus has two pairs of autosomes similar in length and morphology and two sex chromosomes with equal, heterochromatic, late replicating long arms with homologous C-, G-, and Q-bands. The short arm of the Y is shorter than that of the X and both are euchromatic. The mean number of chiasmata per cell in the male is 3.2. During mitosis there is a high grade of somatic pairing but X and Y, which form a heteropycnotic mass in the interphase nucleus, have a differential behaviour. The chronology of DNA replication was studied in spermatogonia and brain cells by autoradiography. It is hypothesized that the present sex chromosomes of A. atroparvus evolved by accumulation of sex determining factors and gene deterioration resulting in heterochromatinization of the long arms, followed by structural rearrangements.--The homology of the two sex chromosomes requires limited dosage compensation which is achieved either as in Drosophila by modifier genes or by accumulation on the short arm of the X, only of female determining factors which do not require dosage compensation.", "contents": "Karotype, DNA replication and origin of sex chromosomes in Anopheles atroparvus. Anopheles atroparvus has two pairs of autosomes similar in length and morphology and two sex chromosomes with equal, heterochromatic, late replicating long arms with homologous C-, G-, and Q-bands. The short arm of the Y is shorter than that of the X and both are euchromatic. The mean number of chiasmata per cell in the male is 3.2. During mitosis there is a high grade of somatic pairing but X and Y, which form a heteropycnotic mass in the interphase nucleus, have a differential behaviour. The chronology of DNA replication was studied in spermatogonia and brain cells by autoradiography. It is hypothesized that the present sex chromosomes of A. atroparvus evolved by accumulation of sex determining factors and gene deterioration resulting in heterochromatinization of the long arms, followed by structural rearrangements.--The homology of the two sex chromosomes requires limited dosage compensation which is achieved either as in Drosophila by modifier genes or by accumulation on the short arm of the X, only of female determining factors which do not require dosage compensation."} {"id": "PMID:1253647", "title": "The location of ribosomal cistrons (rDNA) in chromosomes of the rat.", "content": "In situ hybridization of 3H-labelled ribosomal RNA to the chromosomes of rat bone marrow cells revealed that clusters of ribosomal cistrons (rDNA) are located in the secondary constrictions of chromosomes No. 3 and 12 and near the centromere of chromosome No. 11, both associated with the late DNA-replicating regions. They were not found in Nos. 1, 2, 13, 19, 20, and the Y chromosome.", "contents": "The location of ribosomal cistrons (rDNA) in chromosomes of the rat. In situ hybridization of 3H-labelled ribosomal RNA to the chromosomes of rat bone marrow cells revealed that clusters of ribosomal cistrons (rDNA) are located in the secondary constrictions of chromosomes No. 3 and 12 and near the centromere of chromosome No. 11, both associated with the late DNA-replicating regions. They were not found in Nos. 1, 2, 13, 19, 20, and the Y chromosome."} {"id": "PMID:1253648", "title": "Random distribution of centromere regions at mitosis in cultured cells of Muntiacus muntjak.", "content": "The manner in which centromere regions of mitotic chromosomes are distributed with respect to the age of their DNA was studied. Cells of the Indian deer Muntiacus muntjak, were grown in the presence of bromodeoxyuridine (BrdU) for two generations and stained with the fluorescent dye Hoechst 33258. Chromatids containing \"granddaughter DNA\" appear dim when compared with those containing \"grandparental DNA\". The frequencies of the various anaphase patterns of bright and dim centromere regions were binomially distributed, indicating random distribution of chromatids with respect to the age of their DNA templates.", "contents": "Random distribution of centromere regions at mitosis in cultured cells of Muntiacus muntjak. The manner in which centromere regions of mitotic chromosomes are distributed with respect to the age of their DNA was studied. Cells of the Indian deer Muntiacus muntjak, were grown in the presence of bromodeoxyuridine (BrdU) for two generations and stained with the fluorescent dye Hoechst 33258. Chromatids containing \"granddaughter DNA\" appear dim when compared with those containing \"grandparental DNA\". The frequencies of the various anaphase patterns of bright and dim centromere regions were binomially distributed, indicating random distribution of chromatids with respect to the age of their DNA templates."} {"id": "PMID:1253649", "title": "Sequence of centromere separation of mitotic chromosomes in Chinese hamster.", "content": "Chromosome preparation in late metaphase cells from bone marrow of colcemid treated male Chinese hamsters were used to analyse the sequence of separation of sister centromeres. Chromatids of chromosomes 2 and 1 are the first ones to separate at centromeres, followed by members of group B, D and C. Some acrocentric chromosome is always the last one to separate at the centromere. The data point to a possible correlation between the position of a centromere in the separation sequence in the genome and the amount of centromeric heterochromatin as well as relation to the phenomenon of non-disjunction.", "contents": "Sequence of centromere separation of mitotic chromosomes in Chinese hamster. Chromosome preparation in late metaphase cells from bone marrow of colcemid treated male Chinese hamsters were used to analyse the sequence of separation of sister centromeres. Chromatids of chromosomes 2 and 1 are the first ones to separate at centromeres, followed by members of group B, D and C. Some acrocentric chromosome is always the last one to separate at the centromere. The data point to a possible correlation between the position of a centromere in the separation sequence in the genome and the amount of centromeric heterochromatin as well as relation to the phenomenon of non-disjunction."} {"id": "PMID:1253650", "title": "Electron microscopic studies on the polytene chromosomes of Chironomus thummi salivary glands. I. Ultrastructural mapping.", "content": "The method of ultrathin sections of unsquashed salivary gland polytene chromosomes of Ch. thummi was applied to their ultrastrual mapping. There was a good agreement between electron micrographs and H\u00e4gele's light microscopic map (1970) with respect to the pattern and number of bands. 94% of bands were identified in larval and prepupal chromosomes. In Ch. thummi, band thickness varied from 0.05-0.5 mum. Most characteristic were 0.2-0.3 mum bands. Morphologically, bands were classified as: continuous (frequently with holes and gaps), discrete, dotted and continuous-discrete, discrete-dotted. Band morphology is related to band size, such that smaller bands, as a rule, were also dotted. Bands beginning to puff likewise became dotted. Interbands in unsquashed chromosome sections were from 0.05-0.15 mum. The smallest interbands contained only fibrils, in the larger interbands few granules could be observed. This makes interbands distinguishable from a typical puff with many such granules.", "contents": "Electron microscopic studies on the polytene chromosomes of Chironomus thummi salivary glands. I. Ultrastructural mapping. The method of ultrathin sections of unsquashed salivary gland polytene chromosomes of Ch. thummi was applied to their ultrastrual mapping. There was a good agreement between electron micrographs and H\u00e4gele's light microscopic map (1970) with respect to the pattern and number of bands. 94% of bands were identified in larval and prepupal chromosomes. In Ch. thummi, band thickness varied from 0.05-0.5 mum. Most characteristic were 0.2-0.3 mum bands. Morphologically, bands were classified as: continuous (frequently with holes and gaps), discrete, dotted and continuous-discrete, discrete-dotted. Band morphology is related to band size, such that smaller bands, as a rule, were also dotted. Bands beginning to puff likewise became dotted. Interbands in unsquashed chromosome sections were from 0.05-0.15 mum. The smallest interbands contained only fibrils, in the larger interbands few granules could be observed. This makes interbands distinguishable from a typical puff with many such granules."} {"id": "PMID:1253651", "title": "Gas gangrene infections of the small intestine, colon and rectum.", "content": "Thirty-three cases of gas gangrene infections originating from the small bowel, colon, and rectum are reviewed. The distinction between localized and diffuse, spreading, types of infection is made. The overall mortality rate was 42.4% and mortality was highest for infections following elective bowel resections. Treatment consisted of antibiotics and surgical debridement, with hyperbaric oxygen used as adjunctive therapy for the more serious cases. The importance of early recognition of clostridial infection is stressed as the key to improved survival.", "contents": "Gas gangrene infections of the small intestine, colon and rectum. Thirty-three cases of gas gangrene infections originating from the small bowel, colon, and rectum are reviewed. The distinction between localized and diffuse, spreading, types of infection is made. The overall mortality rate was 42.4% and mortality was highest for infections following elective bowel resections. Treatment consisted of antibiotics and surgical debridement, with hyperbaric oxygen used as adjunctive therapy for the more serious cases. The importance of early recognition of clostridial infection is stressed as the key to improved survival."} {"id": "PMID:1253654", "title": "Intraoperative fiberoptic colonoscopy--\"the difficult polypectomy\".", "content": "An alternative to transcolonic polypectomy, transabdominally directed, transanal colonoscopic polypectomy, for patients who require polyp removal but in whose cases standard colonoscopic approach has failed is presented. The early results are excellent, and the method also can be applied to other patients who have colonic polyps who undergo procedures such as hysterectomy and cholecystectomy.", "contents": "Intraoperative fiberoptic colonoscopy--\"the difficult polypectomy\". An alternative to transcolonic polypectomy, transabdominally directed, transanal colonoscopic polypectomy, for patients who require polyp removal but in whose cases standard colonoscopic approach has failed is presented. The early results are excellent, and the method also can be applied to other patients who have colonic polyps who undergo procedures such as hysterectomy and cholecystectomy."} {"id": "PMID:1253655", "title": "Bone scanning in carcinomas of the colon and rectum.", "content": "Bone scanning has been shown to have a higher rate of accuracy in diagnosing osseous metastatic lesions from carcinomas of the lung and breast. In the present report, we have demonstrated this to be true for osseous metastases from carcinomas of the colon and rectum. We found that a high percentage (75%) of patients who have pelvic or back pain have positive 99mTc bone scans for metastases in spite of the negative radiographs. The previously reported incidence of 5-6% of osseous involvement from these tumors is probably lower than the actual incidence, as these studies were reported without the benefit of bone scanning.", "contents": "Bone scanning in carcinomas of the colon and rectum. Bone scanning has been shown to have a higher rate of accuracy in diagnosing osseous metastatic lesions from carcinomas of the lung and breast. In the present report, we have demonstrated this to be true for osseous metastases from carcinomas of the colon and rectum. We found that a high percentage (75%) of patients who have pelvic or back pain have positive 99mTc bone scans for metastases in spite of the negative radiographs. The previously reported incidence of 5-6% of osseous involvement from these tumors is probably lower than the actual incidence, as these studies were reported without the benefit of bone scanning."} {"id": "PMID:1253656", "title": "Bupivacaine, a long-acting local anesthetic, in anorectal surgery.", "content": "The long-acting local anesthetic, bupivacaine, was used in a series of 467 anorectal patients, both inpatients and outpatients. Bupivacaine was found to be safe and effective. Like other local anesthetics, it has none of the operative and postoperative complications frequently associated with general or spinal anesthetics. Its longer duration of action makes it extremely useful in anorectal operations on hospatilized and non-hospitalized patients. The potential hypertensive effects of using epinephrine in the local anesthetic solution appears to be negated by the calming, hypotensive effects of the intravenously administered sedatives in hospitalized patients.", "contents": "Bupivacaine, a long-acting local anesthetic, in anorectal surgery. The long-acting local anesthetic, bupivacaine, was used in a series of 467 anorectal patients, both inpatients and outpatients. Bupivacaine was found to be safe and effective. Like other local anesthetics, it has none of the operative and postoperative complications frequently associated with general or spinal anesthetics. Its longer duration of action makes it extremely useful in anorectal operations on hospatilized and non-hospitalized patients. The potential hypertensive effects of using epinephrine in the local anesthetic solution appears to be negated by the calming, hypotensive effects of the intravenously administered sedatives in hospitalized patients."} {"id": "PMID:1253657", "title": "Diazepam and local anesthesia in anorectal surgery.", "content": "At the Ferguson Clinic, 161 anorectal procedures utilizing intravenously administered diazepam and lidocaine 0.5%, with epinephrine, 1:200,000, were done. Of the patients so treated 12% needed additional medication in order for anesthesia to be effective. No complication resulted from the use of these combinations. It is recommended that the combination of intravenously administered diazepam with local infection of lidocaine and epinephrine be given wider usage because of its ease of handling and very low complication rate.", "contents": "Diazepam and local anesthesia in anorectal surgery. At the Ferguson Clinic, 161 anorectal procedures utilizing intravenously administered diazepam and lidocaine 0.5%, with epinephrine, 1:200,000, were done. Of the patients so treated 12% needed additional medication in order for anesthesia to be effective. No complication resulted from the use of these combinations. It is recommended that the combination of intravenously administered diazepam with local infection of lidocaine and epinephrine be given wider usage because of its ease of handling and very low complication rate."} {"id": "PMID:1253658", "title": "Incarcerated diaphragmatic hernia: report of an unusual case.", "content": "Traumatic diaphragmatic hernias, although quite common are frequently overlooked as a cause of intestinal obstruction. The hernia may produce significant symptoms acutely or manifest itself many years following the initial injury. A high index of suspicion is necessary to diagnose intestinal obstruction due to incarcerated diaphragmatic hernia. The operation should be performed through the transabdominal approach when hernia occurs acutely, and the transthoracic approach is recommended when herniorrhaphy is performed long after the time of injury. A case of incarcerated traumatic diaphragmatic hernia that occurred 19 years following a gunshot wound of the chest is reported. The intestinal obstruction was initially thought to be due to cancer of the splenic flexure of the colon.", "contents": "Incarcerated diaphragmatic hernia: report of an unusual case. Traumatic diaphragmatic hernias, although quite common are frequently overlooked as a cause of intestinal obstruction. The hernia may produce significant symptoms acutely or manifest itself many years following the initial injury. A high index of suspicion is necessary to diagnose intestinal obstruction due to incarcerated diaphragmatic hernia. The operation should be performed through the transabdominal approach when hernia occurs acutely, and the transthoracic approach is recommended when herniorrhaphy is performed long after the time of injury. A case of incarcerated traumatic diaphragmatic hernia that occurred 19 years following a gunshot wound of the chest is reported. The intestinal obstruction was initially thought to be due to cancer of the splenic flexure of the colon."} {"id": "PMID:1253659", "title": "Total anorectal reconstruction following congenital anorectal anomaly: report of a case.", "content": "Following several unsuccessful postnatal attempts at anoplasty to correct anal atresia with a rectovaginal fistula, the patient, 20 years later, underwent an anorectal sphincteric construction using a gracilis-muscle transplant. The five-stage procedure, which extended over a period of two years, resulted in highly satisfactory continence and full social rehabilitation of the patient. The continence achieved in this case seems to be in contradiction to some of the accepted concepts of the mechanisms of continence.", "contents": "Total anorectal reconstruction following congenital anorectal anomaly: report of a case. Following several unsuccessful postnatal attempts at anoplasty to correct anal atresia with a rectovaginal fistula, the patient, 20 years later, underwent an anorectal sphincteric construction using a gracilis-muscle transplant. The five-stage procedure, which extended over a period of two years, resulted in highly satisfactory continence and full social rehabilitation of the patient. The continence achieved in this case seems to be in contradiction to some of the accepted concepts of the mechanisms of continence."} {"id": "PMID:1253660", "title": "Carcinoembryonic antigen in colorectal practice: report of three cases.", "content": "CEA, in combination with the time-honored barium enema, sigmoidoscopy, rectal examination with guaiac determinations, and thorough clinical history, is a useful tool for the colorectal surgeon in following the progression of disease in both colorectal carcinoma patients and patients who have certain premalignant conditions. In this high-risk group of patients, CEA determinations as well as colonoscopy are becoming increasingly useful. That tumors on the left side are associated with higher CEA levels than those on the right side, due to vascular invasion or the grades of the tumors, and that often CEA antigenicity and severity of symptoms in ulcerative colitis correlate well, are emphasized. Finally, following total colectomy in five cases of ulcerative colitis, all CEA titers decreased to the normal range and have remained there.", "contents": "Carcinoembryonic antigen in colorectal practice: report of three cases. CEA, in combination with the time-honored barium enema, sigmoidoscopy, rectal examination with guaiac determinations, and thorough clinical history, is a useful tool for the colorectal surgeon in following the progression of disease in both colorectal carcinoma patients and patients who have certain premalignant conditions. In this high-risk group of patients, CEA determinations as well as colonoscopy are becoming increasingly useful. That tumors on the left side are associated with higher CEA levels than those on the right side, due to vascular invasion or the grades of the tumors, and that often CEA antigenicity and severity of symptoms in ulcerative colitis correlate well, are emphasized. Finally, following total colectomy in five cases of ulcerative colitis, all CEA titers decreased to the normal range and have remained there."} {"id": "PMID:1253661", "title": "L-dopa-carbidopa: combined therapy for the treatment of Parkinson's disease.", "content": "It is now generally acknowledged that L-Dopa is the therapy of choice for Parkinson's Disease. However, L-Dopa has some short comings: It requires large daily dosage, the therapeutic benefits are achieved only after a delayed onset of 1-2 months, and it has a number of side effects both central and peripheral. In the last few years there has been an intense search for agents that are less toxic, more efficient and more rapidly acting that L-Dopa. The ideal agent has not yet been found. However, a combination therapy with L-Dopa and dopa decarboxylase inhibitors has shown promise. The decarboxylase inhibitors used have a large molecule which does not cross the blood brain barrier. Thus when L-Dopa and the decarboxylase inhibitor are given togehher, peripheral production of dopamine from L-Dopa is inhibited, therefore, rendering L-Dopa more readily and rapidly available for brain metabolism. In the present paper we present the results of the treatment of 50 patients on combined therapy using L-Dopa combined with Carbidopa.", "contents": "L-dopa-carbidopa: combined therapy for the treatment of Parkinson's disease. It is now generally acknowledged that L-Dopa is the therapy of choice for Parkinson's Disease. However, L-Dopa has some short comings: It requires large daily dosage, the therapeutic benefits are achieved only after a delayed onset of 1-2 months, and it has a number of side effects both central and peripheral. In the last few years there has been an intense search for agents that are less toxic, more efficient and more rapidly acting that L-Dopa. The ideal agent has not yet been found. However, a combination therapy with L-Dopa and dopa decarboxylase inhibitors has shown promise. The decarboxylase inhibitors used have a large molecule which does not cross the blood brain barrier. Thus when L-Dopa and the decarboxylase inhibitor are given togehher, peripheral production of dopamine from L-Dopa is inhibited, therefore, rendering L-Dopa more readily and rapidly available for brain metabolism. In the present paper we present the results of the treatment of 50 patients on combined therapy using L-Dopa combined with Carbidopa."} {"id": "PMID:1253662", "title": "Treatment of headache pain with auto-acupressure.", "content": "Acupuncture techniques, primarily self-administered acupressure, were evaluated as symptomatic treatment for the pain of migraine, histamine cephalgia, and tension headaches. A twenty-four month study was conducted with a general neuropsychiatric outpatient practice of more than 500 patients, seen for more than 5000 outpatient visits; more than 200 patients had significant headache symptomatology. Appropriate pharmacologic, dietary and psychotherapeutic treatments were administered for underlying metabolic, neurologic and psychiatric disorders. The results of the study indicated that acupuncture techniques were reasonably effective in relieving the pain of migraine and tension headaches. Auto-acupressure replaced outpatient prescriptions for analgesics, ergotamine preparations, steroids, propanolol or methysgeride. The value of auto-acupressure was enhanced by its easy availability of application and lack of toxic effects.", "contents": "Treatment of headache pain with auto-acupressure. Acupuncture techniques, primarily self-administered acupressure, were evaluated as symptomatic treatment for the pain of migraine, histamine cephalgia, and tension headaches. A twenty-four month study was conducted with a general neuropsychiatric outpatient practice of more than 500 patients, seen for more than 5000 outpatient visits; more than 200 patients had significant headache symptomatology. Appropriate pharmacologic, dietary and psychotherapeutic treatments were administered for underlying metabolic, neurologic and psychiatric disorders. The results of the study indicated that acupuncture techniques were reasonably effective in relieving the pain of migraine and tension headaches. Auto-acupressure replaced outpatient prescriptions for analgesics, ergotamine preparations, steroids, propanolol or methysgeride. The value of auto-acupressure was enhanced by its easy availability of application and lack of toxic effects."} {"id": "PMID:1253663", "title": "Seizure disorders associated with neurosyphilis.", "content": "Sixty-eight of 282 neurosyphilitic patients (24.1%) had repetitive adult onset seizures of unknown cause. Serum and CSF FTA-ABS were more accurate diagnostic tests than the non-treponemal serologic tests. The latter tests were reactive in only 54.5% of patients. In addition to standard anticonvulsants, the patients received 20-24 million units procain penicillin G IM during a three week period. The therapeutic failure rate among these patients was 17.3% in contrast to the nonsyphilitic patients who had 21.8-38.6% failure rates. The prognosis of seizures in GPI patients was the worst regardless of the form of treatment. The use of serum and CSF FTA-ABS is recommended as a part of diagnostic evaluation of adult-onset seizure disorders. The use of large doses of penicillin seems to improve the results of treatment.", "contents": "Seizure disorders associated with neurosyphilis. Sixty-eight of 282 neurosyphilitic patients (24.1%) had repetitive adult onset seizures of unknown cause. Serum and CSF FTA-ABS were more accurate diagnostic tests than the non-treponemal serologic tests. The latter tests were reactive in only 54.5% of patients. In addition to standard anticonvulsants, the patients received 20-24 million units procain penicillin G IM during a three week period. The therapeutic failure rate among these patients was 17.3% in contrast to the nonsyphilitic patients who had 21.8-38.6% failure rates. The prognosis of seizures in GPI patients was the worst regardless of the form of treatment. The use of serum and CSF FTA-ABS is recommended as a part of diagnostic evaluation of adult-onset seizure disorders. The use of large doses of penicillin seems to improve the results of treatment."} {"id": "PMID:1253665", "title": "Quantitative dimensions of alcohol use for hospitalized problem drinkers.", "content": "Estimates of lifetime drinking quantities were obtained from two samples of hospitalized drinkers by personal interview. Estimates had high reliability and may significantly correlate with actual amounts. Group parameters for two samples were similar. Individuals show considerable differences from each other on all measures. Drinking quantities often remain stable from year to year, and the changes that do occur include both increases and decreases, usually by small amounts. There are occasional sharp increases in some subjects. The upper limits of drinking may be as high as three quarts of 1200 proof per day for a person over 200 lbs. There is great quantitative diversity among those labeled \"alcoholic.\" It is more useful to view drinking within a quantitative continuum, and discard the presently accepted dichotomy which arbitrarily divides drinkers into the two classes of normal and abnormal. Drinking quantities would be associated with probable social and physical damage along the drinking continuum. It would not be necessary to view those at the extreme of the continuum as qualitatively different from other drinkers, but as quantitatively different. The relationship between quantity and the adverse consequences of drinking are not simple. The harm that any quantity of alcohol can cause may depend also on other factors. Drinking may be viewed as a learned behavior that is a response to on-going events within the person's environment, rather than a symptom of an underlying disease process. It is regulated like other conditioned behaviors by the effects which it produces. The occurrence of this persistent non-adaptive behavior can be explained by the principals of learning theory, making it unnecessary to suppose an underlying disease process to account for such behavior.", "contents": "Quantitative dimensions of alcohol use for hospitalized problem drinkers. Estimates of lifetime drinking quantities were obtained from two samples of hospitalized drinkers by personal interview. Estimates had high reliability and may significantly correlate with actual amounts. Group parameters for two samples were similar. Individuals show considerable differences from each other on all measures. Drinking quantities often remain stable from year to year, and the changes that do occur include both increases and decreases, usually by small amounts. There are occasional sharp increases in some subjects. The upper limits of drinking may be as high as three quarts of 1200 proof per day for a person over 200 lbs. There is great quantitative diversity among those labeled \"alcoholic.\" It is more useful to view drinking within a quantitative continuum, and discard the presently accepted dichotomy which arbitrarily divides drinkers into the two classes of normal and abnormal. Drinking quantities would be associated with probable social and physical damage along the drinking continuum. It would not be necessary to view those at the extreme of the continuum as qualitatively different from other drinkers, but as quantitatively different. The relationship between quantity and the adverse consequences of drinking are not simple. The harm that any quantity of alcohol can cause may depend also on other factors. Drinking may be viewed as a learned behavior that is a response to on-going events within the person's environment, rather than a symptom of an underlying disease process. It is regulated like other conditioned behaviors by the effects which it produces. The occurrence of this persistent non-adaptive behavior can be explained by the principals of learning theory, making it unnecessary to suppose an underlying disease process to account for such behavior."} {"id": "PMID:1253667", "title": "Clinical use of tricyclic antidepressants.", "content": "Tricyclic antidepressants are extremely valuable drugs when they are used in suitable patients, principally those suffering from endogenous depressions. Diagnosis of depression is of major importance in determining the nature of treatment to be used. Differences between most tricyclics are minor for the most part, involving different degrees of sedative or anticholinergic properties. With the exception of doxepin, they are about equally effective in blocking the amine pump mechanism, which is believed to be the pharmacologic action most pertinent to their antidepressant action. A wide range of dose must be explored if patients are to be treated properly. For the most part, doses are defined empirically, either by alleviation of depression or by intolerable side effects. Dosage schedules should be flexible initially but during therapeutic and maintenance periods, single daily doses are possible. Maintenance doses should be reduced to the lowest consistent with continued relief. Treatment should be brief if the episode of depression is the first and is not severe, but may be prolonged for years in patients with a history of frequent and severe recurrences of depression. Other drugs may sometimes be required, and psychological approaches to treatment are always required. ECT should be available for selected instances of severe depression. The hazards of tricyclics are well known and generally are extensions of known pharmacologic effects. Careful prescribing of these drugs can minimize the consequences of suicidal or accidental overdose.", "contents": "Clinical use of tricyclic antidepressants. Tricyclic antidepressants are extremely valuable drugs when they are used in suitable patients, principally those suffering from endogenous depressions. Diagnosis of depression is of major importance in determining the nature of treatment to be used. Differences between most tricyclics are minor for the most part, involving different degrees of sedative or anticholinergic properties. With the exception of doxepin, they are about equally effective in blocking the amine pump mechanism, which is believed to be the pharmacologic action most pertinent to their antidepressant action. A wide range of dose must be explored if patients are to be treated properly. For the most part, doses are defined empirically, either by alleviation of depression or by intolerable side effects. Dosage schedules should be flexible initially but during therapeutic and maintenance periods, single daily doses are possible. Maintenance doses should be reduced to the lowest consistent with continued relief. Treatment should be brief if the episode of depression is the first and is not severe, but may be prolonged for years in patients with a history of frequent and severe recurrences of depression. Other drugs may sometimes be required, and psychological approaches to treatment are always required. ECT should be available for selected instances of severe depression. The hazards of tricyclics are well known and generally are extensions of known pharmacologic effects. Careful prescribing of these drugs can minimize the consequences of suicidal or accidental overdose."} {"id": "PMID:1253673", "title": "Minimal brain dysfunction: a hydraulic parfait model.", "content": "A Venn diagram shows the overlap of MBD, behavior disorders, and learning disorders. A hydraulic parfait model illustrates a concept of symptom production by additive accumulation of pathology from various etiologies. This implies a psychophysiologic disorder. It also implies a multidimensional spectrum of etiologies which could be important for treatment plans in individual cases. A similar hydraulic parfait illustrates a concept of diagnosis-triggering by cumulative pressure from various symptoms. Diagnosticians form a spectrum of \"trigger pulls\", from \"hair trigger\" to \"on safety.\" A useful research effort might be to find a convenient means of developing etiological profiles for individual patients, perhaps by correlation with symptom spectra.", "contents": "Minimal brain dysfunction: a hydraulic parfait model. A Venn diagram shows the overlap of MBD, behavior disorders, and learning disorders. A hydraulic parfait model illustrates a concept of symptom production by additive accumulation of pathology from various etiologies. This implies a psychophysiologic disorder. It also implies a multidimensional spectrum of etiologies which could be important for treatment plans in individual cases. A similar hydraulic parfait illustrates a concept of diagnosis-triggering by cumulative pressure from various symptoms. Diagnosticians form a spectrum of \"trigger pulls\", from \"hair trigger\" to \"on safety.\" A useful research effort might be to find a convenient means of developing etiological profiles for individual patients, perhaps by correlation with symptom spectra."} {"id": "PMID:1253674", "title": "Towards a systems definition of psychiatric practice.", "content": "Assessment of psychiatric practice has been difficult largely because of the apparent diversity of psychiatrists' theories, procedures, and goals. Searching for a unifying principle, we propose system identification failure (SIF), a defect in data-processing, as the unit of psychopathology underlying all psychiatric disorder (and other behavioral error). Definitive treatment must not only identify and correct the data-processing defect, but also eliminate the secondary symptoms. Emphasis is not on method of treatment but on goal or intent. Preparatory treatment includes supportive psychological and environmental measures and somatic therapies (regardless of type, duration, or intensity) which make definitive treatment possible. Palliative treatment must be frequently reviewed. Preventive treatment should prevent SIF-formation. We consider our proposal a distillate of the aims and implicit intent of experienced psychiatrists regardless of their training or theoretical orientation. The search for a functional definition of the practice of psychiatry was perhaps at one time an academic or lexicographic exercise, but, with the advent of peer review, it has become a pragmatic matter deserving of earnest attention. What is psychiatric practice? In a universe criss-crossed by psychiatrists \"riding madly off in all directions.\" not only are the descendants of Anna O. and Dora analyzed in vivo and those of Little Hans at one remove, but also are distant figures and cultures subjected, often iv vitro, to critical scrutiny, while the \"talking treatment\" is applied to couples, families, groups, \"networks\" and communities. When one adds to this the diversity of biological therapies and institutional, environmental, and behavioral manipulations, the task of finding a common theme, much less procedure, becomes a worthy problem in hermeneutics, general semantics, or system analysis. Thus we must ask not only the operational question, \"What do psychiatrists do?\" BUt also, \"What did you to to treat the specific psychopathology of this patient?\" \"Did it work?\" AND, \"Hos do you know?\" Failure to deal with such questions as these will mark psychiatry's inability to cope with a reality that includes Professional Standards Review Organizations and an imminent National Health Insurance...", "contents": "Towards a systems definition of psychiatric practice. Assessment of psychiatric practice has been difficult largely because of the apparent diversity of psychiatrists' theories, procedures, and goals. Searching for a unifying principle, we propose system identification failure (SIF), a defect in data-processing, as the unit of psychopathology underlying all psychiatric disorder (and other behavioral error). Definitive treatment must not only identify and correct the data-processing defect, but also eliminate the secondary symptoms. Emphasis is not on method of treatment but on goal or intent. Preparatory treatment includes supportive psychological and environmental measures and somatic therapies (regardless of type, duration, or intensity) which make definitive treatment possible. Palliative treatment must be frequently reviewed. Preventive treatment should prevent SIF-formation. We consider our proposal a distillate of the aims and implicit intent of experienced psychiatrists regardless of their training or theoretical orientation. The search for a functional definition of the practice of psychiatry was perhaps at one time an academic or lexicographic exercise, but, with the advent of peer review, it has become a pragmatic matter deserving of earnest attention. What is psychiatric practice? In a universe criss-crossed by psychiatrists \"riding madly off in all directions.\" not only are the descendants of Anna O. and Dora analyzed in vivo and those of Little Hans at one remove, but also are distant figures and cultures subjected, often iv vitro, to critical scrutiny, while the \"talking treatment\" is applied to couples, families, groups, \"networks\" and communities. When one adds to this the diversity of biological therapies and institutional, environmental, and behavioral manipulations, the task of finding a common theme, much less procedure, becomes a worthy problem in hermeneutics, general semantics, or system analysis. Thus we must ask not only the operational question, \"What do psychiatrists do?\" BUt also, \"What did you to to treat the specific psychopathology of this patient?\" \"Did it work?\" AND, \"Hos do you know?\" Failure to deal with such questions as these will mark psychiatry's inability to cope with a reality that includes Professional Standards Review Organizations and an imminent National Health Insurance..."} {"id": "PMID:1253700", "title": "[Effect of saralasin on normal blood pressure and on reno-vascular hypertension (author's transl)].", "content": "The angiotensin antagonist saralasin was given intravenously to six normotensive students before and after dietary sodium restriction and to two patients with renovascular hypertension. Both patients responded to the angiotensin antagonist with a decrease of the systolic (32 and 38 mm Hg) and of the diastolic (29 and 16 mm Hg) blood pressure. The small changes in blood pressure observed in the normotensive subjects during the infusion of the angiotensin antagonist indicate that angiotensin II plays no important role in the control of normal blood pressure in recumbent men. The fall in blood pressure induced by saralasin in both patients, however, demonstrates that their hypertension was at least partly angiotensin-dependent. Renal vein renin determination led to the same conclusions. The saralasin infusion test seems to be a simple procedure to diagnose angiotensin-dependent hypertension and will probably help to identify patients with suspected renovascular hypertension.", "contents": "[Effect of saralasin on normal blood pressure and on reno-vascular hypertension (author's transl)]. The angiotensin antagonist saralasin was given intravenously to six normotensive students before and after dietary sodium restriction and to two patients with renovascular hypertension. Both patients responded to the angiotensin antagonist with a decrease of the systolic (32 and 38 mm Hg) and of the diastolic (29 and 16 mm Hg) blood pressure. The small changes in blood pressure observed in the normotensive subjects during the infusion of the angiotensin antagonist indicate that angiotensin II plays no important role in the control of normal blood pressure in recumbent men. The fall in blood pressure induced by saralasin in both patients, however, demonstrates that their hypertension was at least partly angiotensin-dependent. Renal vein renin determination led to the same conclusions. The saralasin infusion test seems to be a simple procedure to diagnose angiotensin-dependent hypertension and will probably help to identify patients with suspected renovascular hypertension."} {"id": "PMID:1253701", "title": "[Treatment of hyperlipoproteinaemia types IIa, IIb, IV and V with a combination of clofibrate and inositol nicotinate (author's transl)].", "content": "Treatment of 14 patients over eight weeks with a combined preparation containing 250 mg clofibrate and 180 mg inositol nicotinate resulted in a decrease of serum-cholesterol level of 20% and of serum triglyceride levels of 40%. The same effect was obtained in 22 patients by clofibrate alone in double doses. There was no significant difference in effect between the two preparations. Doubling the dose of the combined preparation in ten patients did not increase the lipid-lowering effect. After the combined preparation had been stopped triglycerides rose more slowly than after stopping clofibrate alone. There was no difference with regard to the rise in the cholesterol levels. The combined preparation lowered serum lipids regardless of the type of hyperlipoproteinaemia, but the extent was less with types IIa and IIb (n =15) because of the lower initial value, than in those with types IV (n = 26) and V (n = 3).", "contents": "[Treatment of hyperlipoproteinaemia types IIa, IIb, IV and V with a combination of clofibrate and inositol nicotinate (author's transl)]. Treatment of 14 patients over eight weeks with a combined preparation containing 250 mg clofibrate and 180 mg inositol nicotinate resulted in a decrease of serum-cholesterol level of 20% and of serum triglyceride levels of 40%. The same effect was obtained in 22 patients by clofibrate alone in double doses. There was no significant difference in effect between the two preparations. Doubling the dose of the combined preparation in ten patients did not increase the lipid-lowering effect. After the combined preparation had been stopped triglycerides rose more slowly than after stopping clofibrate alone. There was no difference with regard to the rise in the cholesterol levels. The combined preparation lowered serum lipids regardless of the type of hyperlipoproteinaemia, but the extent was less with types IIa and IIb (n =15) because of the lower initial value, than in those with types IV (n = 26) and V (n = 3)."} {"id": "PMID:1253702", "title": "[Haemoglobin M-Homburg (author's transl)].", "content": "Haemoglobin M is a rare cause of congenital cyanosis and is usually misdiagnosed as being due to congenital heart disease. This was also the case in a family on whom this report is based. In five members of three generations the characteristic grey-blue cyanosis was due to a haemoglobin M anomaly. In all of them cardiopulmonary disease, anaemia and haemolysis had been excluded. The amino-acid substitution was in the alpha-chain of the globin molecule. Consequently the carriers of the trait have an abnormal haemoglobin content of 20-25%. Despite marked cyanosis they feel well.", "contents": "[Haemoglobin M-Homburg (author's transl)]. Haemoglobin M is a rare cause of congenital cyanosis and is usually misdiagnosed as being due to congenital heart disease. This was also the case in a family on whom this report is based. In five members of three generations the characteristic grey-blue cyanosis was due to a haemoglobin M anomaly. In all of them cardiopulmonary disease, anaemia and haemolysis had been excluded. The amino-acid substitution was in the alpha-chain of the globin molecule. Consequently the carriers of the trait have an abnormal haemoglobin content of 20-25%. Despite marked cyanosis they feel well."} {"id": "PMID:1253703", "title": "[Leucocyte migration-inhibition test in syphilis (author's transl)].", "content": "The leucocyte migration-inhibition test was performed on blood from 57 patients with syphilis. Even in the early stages of the disease with lymph-node involvement there were signs of cellular antitreponemic reactivity. But there was an absence of cellular immune response in some patients with secondary syphilis and CNS involvement in the course of tertiary syphilis.", "contents": "[Leucocyte migration-inhibition test in syphilis (author's transl)]. The leucocyte migration-inhibition test was performed on blood from 57 patients with syphilis. Even in the early stages of the disease with lymph-node involvement there were signs of cellular antitreponemic reactivity. But there was an absence of cellular immune response in some patients with secondary syphilis and CNS involvement in the course of tertiary syphilis."} {"id": "PMID:1253704", "title": "[Haemoperfusion with activated charcoal and ion exchanger in phalloidin intoxicated rats (author's transl)].", "content": "Amberlite-XAD-4 and activated charcoal haemoperfusion permit a considerable increase in 14C-methyl-phalloin elimination in vitro which surpasses the effect of haemodialysis treatment. However, in the in-vivo experiment using phalloidin intoxicated rats (1.5 or 2.0 mg/kg i.v.) prolongation of the survival period could not be attained 0y haemoperfusion.", "contents": "[Haemoperfusion with activated charcoal and ion exchanger in phalloidin intoxicated rats (author's transl)]. Amberlite-XAD-4 and activated charcoal haemoperfusion permit a considerable increase in 14C-methyl-phalloin elimination in vitro which surpasses the effect of haemodialysis treatment. However, in the in-vivo experiment using phalloidin intoxicated rats (1.5 or 2.0 mg/kg i.v.) prolongation of the survival period could not be attained 0y haemoperfusion."} {"id": "PMID:1253712", "title": "[Occult blood in stool. A field trial in cancer screening (author's transl)].", "content": "4000 male probands aged 45 to 69 were investigated in a field trial according to random distribution for undetected intestinal bleeding with the Haemoccult - method. With a participation of 28% only 39 out of a total of 65 positive cases could be evaluated. Four cases of colon or rectal carcinoma and four cases of colonic polyps were ascertained. In view of complete lack of experience with false negative test results the Haemoccult test is at present a useful addition to the diagnostic possibilities. However, in suspected cases even a repeatedly negative test cannot replace complete colo-rectal investigation.", "contents": "[Occult blood in stool. A field trial in cancer screening (author's transl)]. 4000 male probands aged 45 to 69 were investigated in a field trial according to random distribution for undetected intestinal bleeding with the Haemoccult - method. With a participation of 28% only 39 out of a total of 65 positive cases could be evaluated. Four cases of colon or rectal carcinoma and four cases of colonic polyps were ascertained. In view of complete lack of experience with false negative test results the Haemoccult test is at present a useful addition to the diagnostic possibilities. However, in suspected cases even a repeatedly negative test cannot replace complete colo-rectal investigation."} {"id": "PMID:1253713", "title": "[Clinical course of arteriosclerosis of coronary and lower limb arteries (author's transl)].", "content": "The clinical course of arteriosclerosis was evaluated in 9 patients with coronary sclerosis and in 25 with peripheral arterial occlusive disease by means of repeat angiographies following primary angiography after 22.5 and 36.6 months, respectively. During the period of observation arteriosclerosis had progressed in all cases except in two patients with peripheral arterial occlusive disease. Despite intensive therapeutic efforts including control of risk factors, dietary care, guided or unguided exercise and the attempt to change unsatisfactory living conditions, progression of arteriosclerosis could not be interrupted. If treatment delayed progression of arteriosclerosis cannot be decided. All vascular areas were affected indiscriminately by progression and no particular localisation was preferred. Intensive exercise does not seem to delay progression of arteriosclerosis.", "contents": "[Clinical course of arteriosclerosis of coronary and lower limb arteries (author's transl)]. The clinical course of arteriosclerosis was evaluated in 9 patients with coronary sclerosis and in 25 with peripheral arterial occlusive disease by means of repeat angiographies following primary angiography after 22.5 and 36.6 months, respectively. During the period of observation arteriosclerosis had progressed in all cases except in two patients with peripheral arterial occlusive disease. Despite intensive therapeutic efforts including control of risk factors, dietary care, guided or unguided exercise and the attempt to change unsatisfactory living conditions, progression of arteriosclerosis could not be interrupted. If treatment delayed progression of arteriosclerosis cannot be decided. All vascular areas were affected indiscriminately by progression and no particular localisation was preferred. Intensive exercise does not seem to delay progression of arteriosclerosis."} {"id": "PMID:1253714", "title": "[The influence of coffee and caffeine on gastrin and acid secretion in man (author's transl)].", "content": "Intragastric instillation of coffee, decaffeinated coffee and pure caffeine in humans significantly stimulated gastric secretion. After intragastric caffeine, basal serum gastrin concentrations were not changed. However after instillation of coffee and decaffeinated coffee serum gastrin increased significantly. Thus acid secretion was significantly greater after coffee and decaffeinated coffee than after caffeine. Roasted products seem to be responsible for the gastrin-releasing effect of coffee.", "contents": "[The influence of coffee and caffeine on gastrin and acid secretion in man (author's transl)]. Intragastric instillation of coffee, decaffeinated coffee and pure caffeine in humans significantly stimulated gastric secretion. After intragastric caffeine, basal serum gastrin concentrations were not changed. However after instillation of coffee and decaffeinated coffee serum gastrin increased significantly. Thus acid secretion was significantly greater after coffee and decaffeinated coffee than after caffeine. Roasted products seem to be responsible for the gastrin-releasing effect of coffee."} {"id": "PMID:1253718", "title": "[Indications and limitations of mammography in the diagnosis of breast tumour (author's transl)].", "content": "Malignancy of a palpable, circumscribed, solid breast tumour can be clarified only by diagnostic extripation and subsequent histological examination. None of the known physical methods approaches the histological examination in diagnostic accuracy. Since, however, diagnostic accuracy is as important here as with every form of malignant tumour, mammography is superfluous in case of palable tumour. If results of mammography and palpation are equivocal, it must be decided whether histological examination or expectant waiting for a specified period with serial controls is necessary. The fact that \"small\" carcinomas can be removed surgically may put the patient at risk if this procedure is practised too widely for cosmetic reasons or in the belief that this is sufficient. Yet radical removal is the cardinal requirement in operations for carcinoma of the breast. Radical operation with complete removal of the axillary lymph nodes is thus not a retrogressive step.", "contents": "[Indications and limitations of mammography in the diagnosis of breast tumour (author's transl)]. Malignancy of a palpable, circumscribed, solid breast tumour can be clarified only by diagnostic extripation and subsequent histological examination. None of the known physical methods approaches the histological examination in diagnostic accuracy. Since, however, diagnostic accuracy is as important here as with every form of malignant tumour, mammography is superfluous in case of palable tumour. If results of mammography and palpation are equivocal, it must be decided whether histological examination or expectant waiting for a specified period with serial controls is necessary. The fact that \"small\" carcinomas can be removed surgically may put the patient at risk if this procedure is practised too widely for cosmetic reasons or in the belief that this is sufficient. Yet radical removal is the cardinal requirement in operations for carcinoma of the breast. Radical operation with complete removal of the axillary lymph nodes is thus not a retrogressive step."} {"id": "PMID:1253719", "title": "[Incidence of locally confined growth of carcinoma of the breast (author's transl)].", "content": "In 220 cases of breast carcinoma with an anatomical size of less than 2 cm metastases outside the primarily affected quadrant could be demonstrated in the remaining breast in 23.6% of cases (n = 52). Axillary lymph node metastases were present in 3.93% (n = 86). With a tumour size up to 0.5 cm neither metastases in remaining breast tissue nor lymph node metastases could be found. With a tumour size of 0.6 to 1.0 cm only 32 out of 51 cases (62.7%) could be considered to be locally confined. In tumours between 1.1 and 2 cm there was no spread demonstrable in remaining breast tissue or axillary nodes in 70 out of 164 cases (42.7%).", "contents": "[Incidence of locally confined growth of carcinoma of the breast (author's transl)]. In 220 cases of breast carcinoma with an anatomical size of less than 2 cm metastases outside the primarily affected quadrant could be demonstrated in the remaining breast in 23.6% of cases (n = 52). Axillary lymph node metastases were present in 3.93% (n = 86). With a tumour size up to 0.5 cm neither metastases in remaining breast tissue nor lymph node metastases could be found. With a tumour size of 0.6 to 1.0 cm only 32 out of 51 cases (62.7%) could be considered to be locally confined. In tumours between 1.1 and 2 cm there was no spread demonstrable in remaining breast tissue or axillary nodes in 70 out of 164 cases (42.7%)."} {"id": "PMID:1253720", "title": "[The influence of warm ischaemic time on the results of hypothermic kidney perfusion (author's transl)].", "content": "50 dog kidneys were mechanically perfused under hypothermia for between 12 and 72 h and then transplanted. Before perfusion the kidneys were subjected to 15,30,45 and 60 min of warm ischaemia: 15 min of warm ischaemia were well tolerated (successful 72-h preservation), but after 30 min preservation was successful for only 24 h. Enzyme release and lactate formation depended on the duration of warm ischaemia. Furthermore, these perfusate concentrations indicated the viability of the organ (highly significant differences between well functioning kidneys and those with little or no function.", "contents": "[The influence of warm ischaemic time on the results of hypothermic kidney perfusion (author's transl)]. 50 dog kidneys were mechanically perfused under hypothermia for between 12 and 72 h and then transplanted. Before perfusion the kidneys were subjected to 15,30,45 and 60 min of warm ischaemia: 15 min of warm ischaemia were well tolerated (successful 72-h preservation), but after 30 min preservation was successful for only 24 h. Enzyme release and lactate formation depended on the duration of warm ischaemia. Furthermore, these perfusate concentrations indicated the viability of the organ (highly significant differences between well functioning kidneys and those with little or no function."} {"id": "PMID:1253733", "title": "[Diagnosis of internal carotid artery obstructions (author's transl)].", "content": "The diagnostic value of directional ultrasound Doppler-sonography (UDS) of the supratrochlear (medial frontal) artery was evaluated by examination of 191 angiographically controlled cases in whom a carotid obstruction was suspected. A systematic compression of the facial and temporal arteries of both sides was performed. In 108 cases the UDS findings were normal, 6% of these were false negative and actually had a stenosis (n = 6) or occlusion (n = 2) of the internal carotid artery. In 88% of the pathological findings a stenosis (n = 39) or occlusion (n = 34) of the internal carotid artery was revealed by angiography. 79% of the stenoses were of severe degree (more than 50%). These results show that UDS is a useful diagnostic tool for the detection of severe stenoses or occlusions of the internal carotid artery. A distinction between stenosis and occlusion by UDS of the supratrochlear artery is, however, not possible, unless additional examination of the carotid arteries is performed. The method is not suitable for the detection of low grade stenoses.", "contents": "[Diagnosis of internal carotid artery obstructions (author's transl)]. The diagnostic value of directional ultrasound Doppler-sonography (UDS) of the supratrochlear (medial frontal) artery was evaluated by examination of 191 angiographically controlled cases in whom a carotid obstruction was suspected. A systematic compression of the facial and temporal arteries of both sides was performed. In 108 cases the UDS findings were normal, 6% of these were false negative and actually had a stenosis (n = 6) or occlusion (n = 2) of the internal carotid artery. In 88% of the pathological findings a stenosis (n = 39) or occlusion (n = 34) of the internal carotid artery was revealed by angiography. 79% of the stenoses were of severe degree (more than 50%). These results show that UDS is a useful diagnostic tool for the detection of severe stenoses or occlusions of the internal carotid artery. A distinction between stenosis and occlusion by UDS of the supratrochlear artery is, however, not possible, unless additional examination of the carotid arteries is performed. The method is not suitable for the detection of low grade stenoses."} {"id": "PMID:1253734", "title": "[Guinea-pig asthma (author's transl)].", "content": "Out of 140 selected patients with bronchial asthma 24 demonstrated signs of guinea-pig hypersensitivity. Six further patients with a shorter exposure to guinea-pigs were not sensitized. The diagnosis can be established by means of history, skin test, and removal of the animal. The mean period until asthma became clinically manifest was 12.3 months, for the prodromal stage rhinitis and (or) conjunctivitis 9.8 months. Atopic symptoms may or may not be present in affected persons. A great number of accompanying false-positive skin test reactions to different animal dander antigens supports the hypothesis of an antigenic relationship between dander allergens from different animal species. The only treatment for guinea-pig asthma is removal of the guinea-pig. Other domestic animals should be avoided as well.", "contents": "[Guinea-pig asthma (author's transl)]. Out of 140 selected patients with bronchial asthma 24 demonstrated signs of guinea-pig hypersensitivity. Six further patients with a shorter exposure to guinea-pigs were not sensitized. The diagnosis can be established by means of history, skin test, and removal of the animal. The mean period until asthma became clinically manifest was 12.3 months, for the prodromal stage rhinitis and (or) conjunctivitis 9.8 months. Atopic symptoms may or may not be present in affected persons. A great number of accompanying false-positive skin test reactions to different animal dander antigens supports the hypothesis of an antigenic relationship between dander allergens from different animal species. The only treatment for guinea-pig asthma is removal of the guinea-pig. Other domestic animals should be avoided as well."} {"id": "PMID:1253735", "title": "[Mineral content of bone in long-standing diabetes: densitometry of \"diabetic osteopathy\" (author's transl)].", "content": "Using 125I-photon absorption, skeletal mineral content was measured in 57 diabetics requiring insulin. Average age was 33 years, mean duration of diabetes 19 years. Abnormally reduced mineral content was detected in ten of 21 males and 11 of 36 women. This finding is interpreted as being a late complication of diabetes. Pathological fractures were not seen and there were very few complaints referable to the skeletal system.", "contents": "[Mineral content of bone in long-standing diabetes: densitometry of \"diabetic osteopathy\" (author's transl)]. Using 125I-photon absorption, skeletal mineral content was measured in 57 diabetics requiring insulin. Average age was 33 years, mean duration of diabetes 19 years. Abnormally reduced mineral content was detected in ten of 21 males and 11 of 36 women. This finding is interpreted as being a late complication of diabetes. Pathological fractures were not seen and there were very few complaints referable to the skeletal system."} {"id": "PMID:1253736", "title": "[Innervation anomalies of the thenar muscles (author's transl)].", "content": "In 337 patients various reasons led to an electromyographic investigation of the thenar muscles and frequently of the hypothenar muscles as well. Conduction velocity studies of the median and ulnar nerves were also performed. Five cases were found with concomitant innervation and two cases with exclusive innervation of the opponens pollicis muscle by the ulnar nerve. Two clinical cases in whom a severe median nerve injury has been overlooked due to this anomalous innervation demonstrate the importance of the awareness of this innervation variation.", "contents": "[Innervation anomalies of the thenar muscles (author's transl)]. In 337 patients various reasons led to an electromyographic investigation of the thenar muscles and frequently of the hypothenar muscles as well. Conduction velocity studies of the median and ulnar nerves were also performed. Five cases were found with concomitant innervation and two cases with exclusive innervation of the opponens pollicis muscle by the ulnar nerve. Two clinical cases in whom a severe median nerve injury has been overlooked due to this anomalous innervation demonstrate the importance of the awareness of this innervation variation."} {"id": "PMID:1253737", "title": "[Severe coagulopathy due to inhibitors of several clotting factors in IgM paraproteinaemia (author's transl)].", "content": "A 62-year-old man presented with an IgM paraproteinaemia and then suddenly developed an haemophilia-like haemorrhagic diathesis. Clotting tests revealed markedly prolonged Quick prothrombin times (more than 2 min) and much diminished factor II, V, VII, and X activities. Cross-mixing experiments indicated the presence of a circulating inhibitor, which specifically blocked the activity of these factors. But the exact mechanism remains uncertain, no inhibitor of this type having been previously reported. In addition to the clotting defect there was a probably monoclonal immunoglobulin IgM. Complete remission occurred and has now persisted for 18 months, after immuno-suppressive treatment with azathioprine and prednisone. It is suggested that the inhibitory capacity is confined to the abnormal IgM, due to a primary immunological disorder. A review of similar reported cases emphasizes the importance of immunosuppressive treatment in this disorder.", "contents": "[Severe coagulopathy due to inhibitors of several clotting factors in IgM paraproteinaemia (author's transl)]. A 62-year-old man presented with an IgM paraproteinaemia and then suddenly developed an haemophilia-like haemorrhagic diathesis. Clotting tests revealed markedly prolonged Quick prothrombin times (more than 2 min) and much diminished factor II, V, VII, and X activities. Cross-mixing experiments indicated the presence of a circulating inhibitor, which specifically blocked the activity of these factors. But the exact mechanism remains uncertain, no inhibitor of this type having been previously reported. In addition to the clotting defect there was a probably monoclonal immunoglobulin IgM. Complete remission occurred and has now persisted for 18 months, after immuno-suppressive treatment with azathioprine and prednisone. It is suggested that the inhibitory capacity is confined to the abnormal IgM, due to a primary immunological disorder. A review of similar reported cases emphasizes the importance of immunosuppressive treatment in this disorder."} {"id": "PMID:1253775", "title": "Spatial vector changes during ventricular depolarisation using a semi-orthogonal lead system--a study of 190 cases.", "content": "The paper describes the spatial vector changes during ventricular depolarisation in 190 horses using a semi-orthogonal ECG lead system. The replacement of planar vector loops by a plot of 3 parameters to depict the changing spatial vector, with a time base on the X axis, is described and illustrated. Some horses with diastolic murmurs and some with a history of respiratory problems formed 2 distinct groups. As a result of these findings a possible relationship between the vector changes and the anatomical siting of the ventricles is suggested and discussed. Attention is drawn to certain measurements which appear to have possible use in assessing the significance of cardiac electrical activity in relation to changes in the ventricular myocardium.", "contents": "Spatial vector changes during ventricular depolarisation using a semi-orthogonal lead system--a study of 190 cases. The paper describes the spatial vector changes during ventricular depolarisation in 190 horses using a semi-orthogonal ECG lead system. The replacement of planar vector loops by a plot of 3 parameters to depict the changing spatial vector, with a time base on the X axis, is described and illustrated. Some horses with diastolic murmurs and some with a history of respiratory problems formed 2 distinct groups. As a result of these findings a possible relationship between the vector changes and the anatomical siting of the ventricles is suggested and discussed. Attention is drawn to certain measurements which appear to have possible use in assessing the significance of cardiac electrical activity in relation to changes in the ventricular myocardium."} {"id": "PMID:1253776", "title": "The surgical treatment of fractures of the olecranon in the horse.", "content": "Methods of treating fractures of the olecranon in the horse are reviewed. A further 4 cases are recorded in which the fracture was treated by open reduction and fixation with a heavy duty Venable's plate placed on the caudal aspect of the ulna. Three cases had an oblique fracture through the semilunar notch; this was complicated in one by a fracture of the lateral half of the radial head which resulted in subluxation of the radio-humeral joint. The fracture of the radial head was treated by open reduction and fixation with a lag screw. The fourth case had an oblique fracture of the olecranon just proximal to the semilunar notch, complicated by a fracture of the anconeal process which was removed. The fractures healed within 10 weeks and the plates were removed in all 4 cases. During follow-up periods ranging from 10 to 26 months, all 4 animals became sound.", "contents": "The surgical treatment of fractures of the olecranon in the horse. Methods of treating fractures of the olecranon in the horse are reviewed. A further 4 cases are recorded in which the fracture was treated by open reduction and fixation with a heavy duty Venable's plate placed on the caudal aspect of the ulna. Three cases had an oblique fracture through the semilunar notch; this was complicated in one by a fracture of the lateral half of the radial head which resulted in subluxation of the radio-humeral joint. The fracture of the radial head was treated by open reduction and fixation with a lag screw. The fourth case had an oblique fracture of the olecranon just proximal to the semilunar notch, complicated by a fracture of the anconeal process which was removed. The fractures healed within 10 weeks and the plates were removed in all 4 cases. During follow-up periods ranging from 10 to 26 months, all 4 animals became sound."} {"id": "PMID:1253777", "title": "Behaviour of the heart rate of horses with auricular fibrillation during exercise and after treatment.", "content": "Cardioversion through varying quinidine sulphate treatments was achieved in 3 riding horses with auricular fibrillation. The horses were subjected to continual telemetric ECG registration before and after reversion in a uniform exercise-tolerance-test. A comparison of the heart rate curves showed a strong decline of the heart beat frequency during the exercise phase after synchronisation. The decrease in heart rate during exercise was greater than 30% in all 3 patients. Anti-arrhythmic treatment is, therefore, recommended for horses with auricular fibrillation and without concurrent heart disease.", "contents": "Behaviour of the heart rate of horses with auricular fibrillation during exercise and after treatment. Cardioversion through varying quinidine sulphate treatments was achieved in 3 riding horses with auricular fibrillation. The horses were subjected to continual telemetric ECG registration before and after reversion in a uniform exercise-tolerance-test. A comparison of the heart rate curves showed a strong decline of the heart beat frequency during the exercise phase after synchronisation. The decrease in heart rate during exercise was greater than 30% in all 3 patients. Anti-arrhythmic treatment is, therefore, recommended for horses with auricular fibrillation and without concurrent heart disease."} {"id": "PMID:1253778", "title": "Studies on erythrocyte metabolism following acute blood loss in the horse.", "content": "Anaemic horses do not provide reticulocytes during an erythropietic response. Acute blood loss was studied in 4 ponies as a model to monitor changes in erythrocyte metabolism during active erythropoiesis. Following phlebotomy, erythrocyte adenosine-5-triphosphate, adenosine-5-diphosphate, glucose-6-phosphate, fructose-6-phosphate, and phosphoenolpyruvate increased signifcantly. The remaining glycolytic intermediates did not change. It is suggested that the determination of erythrocyte adenosine-5-triphosphate may be used to evaluate erythrocyte response following acute blood loss in the horse.", "contents": "Studies on erythrocyte metabolism following acute blood loss in the horse. Anaemic horses do not provide reticulocytes during an erythropietic response. Acute blood loss was studied in 4 ponies as a model to monitor changes in erythrocyte metabolism during active erythropoiesis. Following phlebotomy, erythrocyte adenosine-5-triphosphate, adenosine-5-diphosphate, glucose-6-phosphate, fructose-6-phosphate, and phosphoenolpyruvate increased signifcantly. The remaining glycolytic intermediates did not change. It is suggested that the determination of erythrocyte adenosine-5-triphosphate may be used to evaluate erythrocyte response following acute blood loss in the horse."} {"id": "PMID:1253779", "title": "Isometric strength and endurance during the menstrual cycle.", "content": "Seven healthy young women, 3 whom had been taking oral contraceptives, were examined during the course of 2 menstrual cycles to assess their isometric strength, their endurance during a series of 5 fatiguing isometric contractions at a tension of 40% MVC, and their blood pressures and heart rates during those fatiguing contractions. Two sets of experiments were performed, one in which the subject's forearm temperature was allowed to vary as a function of T A, and one with the muscle temperature stabilized by immersion of the forearm in water at 37 degrees C. During exposure to ambient temperatures, isometric strength and both the heart rate and blood pressure responses at rest and at the end of a fatiguing, sustained isometric exercise, were not significantly different during any phase of the menstrual cycle in any subject. In contrast, the isometric endurance in the women not taking oral contraceptives varied sinusoidally in all 5 contractions with a peak endurance midway through the ovulatory phase and the lowest endurance mid-way through the luteal phase of the menstrual cycle. The isometric endurance of the women taking oral contraceptives did not vary during their menstrual cycle. After stabilization of the temperature of the muscles of the forearm in water at 37 degrees C, the isometric endurance of the normal subjects showed a hyperbolic response with the maximal endurance at the beginning and end of their cycles, and the shortest endurance at mid-cycle. Here again, however, the isometric endurance of the women taking oral contraceptives did not vary after immersion of their forearms in the 37 degree C water.", "contents": "Isometric strength and endurance during the menstrual cycle. Seven healthy young women, 3 whom had been taking oral contraceptives, were examined during the course of 2 menstrual cycles to assess their isometric strength, their endurance during a series of 5 fatiguing isometric contractions at a tension of 40% MVC, and their blood pressures and heart rates during those fatiguing contractions. Two sets of experiments were performed, one in which the subject's forearm temperature was allowed to vary as a function of T A, and one with the muscle temperature stabilized by immersion of the forearm in water at 37 degrees C. During exposure to ambient temperatures, isometric strength and both the heart rate and blood pressure responses at rest and at the end of a fatiguing, sustained isometric exercise, were not significantly different during any phase of the menstrual cycle in any subject. In contrast, the isometric endurance in the women not taking oral contraceptives varied sinusoidally in all 5 contractions with a peak endurance midway through the ovulatory phase and the lowest endurance mid-way through the luteal phase of the menstrual cycle. The isometric endurance of the women taking oral contraceptives did not vary during their menstrual cycle. After stabilization of the temperature of the muscles of the forearm in water at 37 degrees C, the isometric endurance of the normal subjects showed a hyperbolic response with the maximal endurance at the beginning and end of their cycles, and the shortest endurance at mid-cycle. Here again, however, the isometric endurance of the women taking oral contraceptives did not vary after immersion of their forearms in the 37 degree C water."} {"id": "PMID:1253780", "title": "An apparatus and a method for measuring the relationship of triceps surae torques to tibio-tarsal angles in man.", "content": "1. The apparatus and method described give the relationship of triceps surae torque to the absolute tibio-tarsal angle. Data of the anatomy of the foot and the axis of the ankle are taken into consideration. They make complementary measurements necessary, which in certain cases enable the angle recorded by the apparatus to be corrected so as to obtain the true angle. 2. The reliability of the apparatus and the technique of linkage of subject to apparatus are judged by examination of the torque-angle plots obtained by passive stretching of the triceps in 7 subjects for whom correction is monor. Good reliability was observed during the session and from one session to another. The plot is exponential. The merits of the method of correcting angles are illustrated in three subjects with the same protocol: when plots are not corrected, they are more dispersed during the session and no longer exponential. These results justify the considerable correction of the angle that we propose in the study of isometric contractions.", "contents": "An apparatus and a method for measuring the relationship of triceps surae torques to tibio-tarsal angles in man. 1. The apparatus and method described give the relationship of triceps surae torque to the absolute tibio-tarsal angle. Data of the anatomy of the foot and the axis of the ankle are taken into consideration. They make complementary measurements necessary, which in certain cases enable the angle recorded by the apparatus to be corrected so as to obtain the true angle. 2. The reliability of the apparatus and the technique of linkage of subject to apparatus are judged by examination of the torque-angle plots obtained by passive stretching of the triceps in 7 subjects for whom correction is monor. Good reliability was observed during the session and from one session to another. The plot is exponential. The merits of the method of correcting angles are illustrated in three subjects with the same protocol: when plots are not corrected, they are more dispersed during the session and no longer exponential. These results justify the considerable correction of the angle that we propose in the study of isometric contractions."} {"id": "PMID:1253781", "title": "[Changes in serum proteins,-iron and -copper in swimmers before and after altitude training (author's transl)].", "content": "Fifteen male swimmers (mean age 19.3 +/- 2.1 years) were subjected to a standard 120 min swimming exercise test: a) before, and b) after 5 weeks of intensive training at middle altitude (2000 m). At rest, serum levels of alpha2-macroglobulin, transferrin and copper were elevated in swimmers as compared to untrained subjects. After the altitude training program, significant increases of the parameters of iron and copper metabolism, as well as of alpha2HS-glycoprotein and beta1A-globulin were observed. After the first exercise test (a), a significant rise in serum alpha1-acid glycoprotein, alpha1-antitrypsin, hemopexin, alpha2-macroglobulin, ceruloplasmin, transferrin, iron, copper and alpha2-HS-glycoprotein was noted. The same 120 min-exercise test after the altitude training (b) led to only small changes, especially as concerns the parameters of iron metabolism. The characteristic immediate and long-lasting changes in serum proteins and heavy metals in swimmers and the effects of training in middle altitude on the answer of the organism to swimming exercise with respect to the mentioned biochemical parameters are discussed.", "contents": "[Changes in serum proteins,-iron and -copper in swimmers before and after altitude training (author's transl)]. Fifteen male swimmers (mean age 19.3 +/- 2.1 years) were subjected to a standard 120 min swimming exercise test: a) before, and b) after 5 weeks of intensive training at middle altitude (2000 m). At rest, serum levels of alpha2-macroglobulin, transferrin and copper were elevated in swimmers as compared to untrained subjects. After the altitude training program, significant increases of the parameters of iron and copper metabolism, as well as of alpha2HS-glycoprotein and beta1A-globulin were observed. After the first exercise test (a), a significant rise in serum alpha1-acid glycoprotein, alpha1-antitrypsin, hemopexin, alpha2-macroglobulin, ceruloplasmin, transferrin, iron, copper and alpha2-HS-glycoprotein was noted. The same 120 min-exercise test after the altitude training (b) led to only small changes, especially as concerns the parameters of iron metabolism. The characteristic immediate and long-lasting changes in serum proteins and heavy metals in swimmers and the effects of training in middle altitude on the answer of the organism to swimming exercise with respect to the mentioned biochemical parameters are discussed."} {"id": "PMID:1253782", "title": "[Adaption of subjects in field studies of informatory working conditions (author's transl)].", "content": "Processes of adaption in measurements of performance - cycle-times, variance of cycle-times, informatory component of time and errors - and of physiological strain - electromyograms of musculus extensor digitorum and musculus rhomboideus, horizontal and vertical electrooculogram, heart rate and heart rate variability - are presented and described in type and frequency. Simultaneous reactions and successive reactions of measured variables in dependance of shift-time and of days are described. They are classified according to the causes \"exercise\" and \"emotional habituation\" and discussed in a model \"experimenter - experimental situation\".", "contents": "[Adaption of subjects in field studies of informatory working conditions (author's transl)]. Processes of adaption in measurements of performance - cycle-times, variance of cycle-times, informatory component of time and errors - and of physiological strain - electromyograms of musculus extensor digitorum and musculus rhomboideus, horizontal and vertical electrooculogram, heart rate and heart rate variability - are presented and described in type and frequency. Simultaneous reactions and successive reactions of measured variables in dependance of shift-time and of days are described. They are classified according to the causes \"exercise\" and \"emotional habituation\" and discussed in a model \"experimenter - experimental situation\"."} {"id": "PMID:1253783", "title": "Physical performance capacity of children in Norway. Part IV. The rate of growth in maximal aerobic power and the influence of improved physical education of children in a rural community - population parameters in a rural community.", "content": "During a period of 4 years the annual increase of the physical performance of 31 boys and 34 girls was examined in a longitudinal study. In spite of the expected mean increase of the physical performance unsystematic annual variations of the increase of the maximal oxygen uptake related to body weight were observed. These variations can only be explained by the variations of the daily physical activity. The fact that in the longitudinal study a clear better performance over the years was observed than in a cross sectional study which was performed in the first year of the longitudinal study confirms this tendency. This can partly be explained by the improvement of the possibilities for physical activities in the community since the begin of the longitudinal study.", "contents": "Physical performance capacity of children in Norway. Part IV. The rate of growth in maximal aerobic power and the influence of improved physical education of children in a rural community - population parameters in a rural community. During a period of 4 years the annual increase of the physical performance of 31 boys and 34 girls was examined in a longitudinal study. In spite of the expected mean increase of the physical performance unsystematic annual variations of the increase of the maximal oxygen uptake related to body weight were observed. These variations can only be explained by the variations of the daily physical activity. The fact that in the longitudinal study a clear better performance over the years was observed than in a cross sectional study which was performed in the first year of the longitudinal study confirms this tendency. This can partly be explained by the improvement of the possibilities for physical activities in the community since the begin of the longitudinal study."} {"id": "PMID:1253784", "title": "Measurement of gas free body volume by a diving device.", "content": "A device is presented for determination of gas free body volume, by which total body volume as well as lung volume together with intestinal gas can be measured. The measurement is performed under water. The subject to be measured keeps his head in an airfilled cylinder which allows free breathing during the measurement procedure under water. The subject sits on a seat which is connected with a vertical \"probe\" that is submerged in a water basin. This \"body density probe\" carries several measuring rods of different diameter on its upper end, which lead to an increase of buoyancy when sinking deeper into the water after additional weights have been put on the device. These rods lead to new equilibrium states which are also dependent on the compressable gas volume attached to the probe. Three equilibrium states with different added weights give a physical definition of gas free body volume, which can be calculated from a number of accurately measurable single items.", "contents": "Measurement of gas free body volume by a diving device. A device is presented for determination of gas free body volume, by which total body volume as well as lung volume together with intestinal gas can be measured. The measurement is performed under water. The subject to be measured keeps his head in an airfilled cylinder which allows free breathing during the measurement procedure under water. The subject sits on a seat which is connected with a vertical \"probe\" that is submerged in a water basin. This \"body density probe\" carries several measuring rods of different diameter on its upper end, which lead to an increase of buoyancy when sinking deeper into the water after additional weights have been put on the device. These rods lead to new equilibrium states which are also dependent on the compressable gas volume attached to the probe. Three equilibrium states with different added weights give a physical definition of gas free body volume, which can be calculated from a number of accurately measurable single items."} {"id": "PMID:1253785", "title": "Changes of free amino acids in plasma of healthy subjects induced by physical exercise.", "content": "In eight healthy men a 20-min load of 1.5 W/kg body weight on a bicycle ergometer led to a significant increase of alanine and decline of leucine. Exhausting exercise caused in the same subjects a highly significant increase of alanine and decline of isoleucine, threonine, ornithine, leucine, serine, glycine, and asparasine and glutamine. The methionine and citrulline level declines also significantly. The total amino acids practically did not change. Physical exercise led furthermore to a marked increase of serum ammonia and uric acid. Urea nitrogen changed only little and on average had rather a declining tendency. The rise of alanine suggests the existence of a glucose-alanine cycle, the drop of ornithine and citrulline is most probably associated with the inhibition of ureogenesis in the liver. The reduction of leucine and isoleucine is probably the result of the entry of these amino acids into muscle and their deamination.", "contents": "Changes of free amino acids in plasma of healthy subjects induced by physical exercise. In eight healthy men a 20-min load of 1.5 W/kg body weight on a bicycle ergometer led to a significant increase of alanine and decline of leucine. Exhausting exercise caused in the same subjects a highly significant increase of alanine and decline of isoleucine, threonine, ornithine, leucine, serine, glycine, and asparasine and glutamine. The methionine and citrulline level declines also significantly. The total amino acids practically did not change. Physical exercise led furthermore to a marked increase of serum ammonia and uric acid. Urea nitrogen changed only little and on average had rather a declining tendency. The rise of alanine suggests the existence of a glucose-alanine cycle, the drop of ornithine and citrulline is most probably associated with the inhibition of ureogenesis in the liver. The reduction of leucine and isoleucine is probably the result of the entry of these amino acids into muscle and their deamination."} {"id": "PMID:1253786", "title": "Pulmonary O2 diffusing capacity at exercise by a modified rebreathing method.", "content": "The rebreathing technique for the measurement of the pulmonary O2 diffusing capacity, DO2, previously developed for resting conditions [Cerretelli et al., J. appl. Physiol. 37, 526-532 (1974)] has been modified for application to exercise and simplified to one rebreathing maneuver only. The changes consist: 1) in administering in the course of a normoxic exercise a priming breath of an O2 free mixture just before the onset of rebreathing in order to achieve rapidly the appropriate starting PO2 values on the linear part of the O2 dissociation curve as required by the method; 2) in calculating mixed venous blood O2 tension by extrapolation of the alveolar to mixed venous blood PO2 equilibration curve, instead of determining it separately. While the mean DO2 value of 21 measurements on 5 subjects at rest was 30 ml-min-1 - Torr-1 +/- 3 (S.E.), in 2 subjects exercising on a bicycle ergometer, DO2 was found to increase from a resting value of about 32 ml- min-1 - Torr-1 to 107 ml - min-1 - Torr-1 for an eightfold increase of O2 uptake. The validity and the applicability of the method are critically discussed.", "contents": "Pulmonary O2 diffusing capacity at exercise by a modified rebreathing method. The rebreathing technique for the measurement of the pulmonary O2 diffusing capacity, DO2, previously developed for resting conditions [Cerretelli et al., J. appl. Physiol. 37, 526-532 (1974)] has been modified for application to exercise and simplified to one rebreathing maneuver only. The changes consist: 1) in administering in the course of a normoxic exercise a priming breath of an O2 free mixture just before the onset of rebreathing in order to achieve rapidly the appropriate starting PO2 values on the linear part of the O2 dissociation curve as required by the method; 2) in calculating mixed venous blood O2 tension by extrapolation of the alveolar to mixed venous blood PO2 equilibration curve, instead of determining it separately. While the mean DO2 value of 21 measurements on 5 subjects at rest was 30 ml-min-1 - Torr-1 +/- 3 (S.E.), in 2 subjects exercising on a bicycle ergometer, DO2 was found to increase from a resting value of about 32 ml- min-1 - Torr-1 to 107 ml - min-1 - Torr-1 for an eightfold increase of O2 uptake. The validity and the applicability of the method are critically discussed."} {"id": "PMID:1253787", "title": "Hamster brown-adipose-tissue mitochondria. Purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide binding site.", "content": "The inner membrane of hamster brown adipose tissue mitochondria possesses a mechanism for the conductance of protons (or hydroxyl ions) and halide anions which may be specifically inhibited by exogenous purine nucleoside di- or triphosphates. The mechanism of the nucleotide interaction is examined. The added nucleotides can inhibit the ion conductances without equilibrating with the matrix pools of purine nucleotides. ADP translocation is completely sensitive to atractylate, and no mechanism for GDP translocation could be detected. The nucleotides act on the conductance mechanism without covalent modification. A purine nucleotide binding site is described which is distinct from the adenine nucleotide translocase, does not bind atractylate, has a capacity of 0.7 nmol - mg-1, and affinities, specificities and a pH dependency closely corresponding to the conditions required for the inhibition of the ion conductances. The binding site is not apparent in rat liver mitochondria. A causal relationship is suggested between the occupation of this site by added purine nucleotides, and the inhibition of the ion conductance pathway. The role of the pathway in the physiological control of non-shivering thermogenesis by the tissue is discussed.", "contents": "Hamster brown-adipose-tissue mitochondria. Purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide binding site. The inner membrane of hamster brown adipose tissue mitochondria possesses a mechanism for the conductance of protons (or hydroxyl ions) and halide anions which may be specifically inhibited by exogenous purine nucleoside di- or triphosphates. The mechanism of the nucleotide interaction is examined. The added nucleotides can inhibit the ion conductances without equilibrating with the matrix pools of purine nucleotides. ADP translocation is completely sensitive to atractylate, and no mechanism for GDP translocation could be detected. The nucleotides act on the conductance mechanism without covalent modification. A purine nucleotide binding site is described which is distinct from the adenine nucleotide translocase, does not bind atractylate, has a capacity of 0.7 nmol - mg-1, and affinities, specificities and a pH dependency closely corresponding to the conditions required for the inhibition of the ion conductances. The binding site is not apparent in rat liver mitochondria. A causal relationship is suggested between the occupation of this site by added purine nucleotides, and the inhibition of the ion conductance pathway. The role of the pathway in the physiological control of non-shivering thermogenesis by the tissue is discussed."} {"id": "PMID:1253788", "title": "Evidence that DNA polymerase-alpha of calf thymus contains a subunit of molecular weight 155000.", "content": "Small samples of the 8-S species of enzymes (A1 and A2) occurring in the DNA polymerase-alpha fraction of calf thymus, have been extensively purified using non-denaturing (normal) polyacrylamide gel electrophoresis. When peak fractions of activity on normal gels were subjected to dodecylsulphate-polyacrylamide gel electrophoresis, a polypeptide at 155000 correlated with polymerase activity. Samples of the 7.3-S (C) enzyme prepared from A2 by treatment with 2.4 M urea or isolated directly without exposure to urea, also showed the presence of a 155000-Mr polypeptide. It is concluded that the 7.3-S (C) enzyme, of previously estimated molecular weight 155000-170000, is a single polypeptide and that the 8-S enzymes A1 and A2 contain an additional subunit of 50000-70000 molecular weight.", "contents": "Evidence that DNA polymerase-alpha of calf thymus contains a subunit of molecular weight 155000. Small samples of the 8-S species of enzymes (A1 and A2) occurring in the DNA polymerase-alpha fraction of calf thymus, have been extensively purified using non-denaturing (normal) polyacrylamide gel electrophoresis. When peak fractions of activity on normal gels were subjected to dodecylsulphate-polyacrylamide gel electrophoresis, a polypeptide at 155000 correlated with polymerase activity. Samples of the 7.3-S (C) enzyme prepared from A2 by treatment with 2.4 M urea or isolated directly without exposure to urea, also showed the presence of a 155000-Mr polypeptide. It is concluded that the 7.3-S (C) enzyme, of previously estimated molecular weight 155000-170000, is a single polypeptide and that the 8-S enzymes A1 and A2 contain an additional subunit of 50000-70000 molecular weight."} {"id": "PMID:1253789", "title": "N-acetyl-9-O-L-lactylneuraminic acid, a new acylneuraminic acid from bovine submandibular gland.", "content": "The acylneuraminic acid fraction, obtained on mild acid hydrolysis of glycoproteins from bovine submandibular glands, contains approximately 2% N-acety-9-O-L-lactylneuraminic acid. The compound has been isolated and purified by ion-exchange and cellulose column chromatography. The structure has been elucidated using thin-layer chromatography, colorimetry, gas-liquid chromatography/mass spectrometry, periodate oxidation and specific lactate dehydrogenases. An evaluation of the different analytical methods is given.", "contents": "N-acetyl-9-O-L-lactylneuraminic acid, a new acylneuraminic acid from bovine submandibular gland. The acylneuraminic acid fraction, obtained on mild acid hydrolysis of glycoproteins from bovine submandibular glands, contains approximately 2% N-acety-9-O-L-lactylneuraminic acid. The compound has been isolated and purified by ion-exchange and cellulose column chromatography. The structure has been elucidated using thin-layer chromatography, colorimetry, gas-liquid chromatography/mass spectrometry, periodate oxidation and specific lactate dehydrogenases. An evaluation of the different analytical methods is given."} {"id": "PMID:1253790", "title": "The binding of Met-tRNAf to isolated 40-S ribosomal subunits and the formation of Met-tRNAf - 80-S-ribosome initiation complexes.", "content": "Different forms of 40-S ribosomal subunit, distinguishable by their buoyant densities on CsCl equilibrium density gradients, are formed when derived 40-S ribosomal subunits are incubated with partially purified reticulocyte ribosomal wash proteins. One of these subunits, the 1.37-g-cm-3 form is not present in the cell but the other two forms, the 1.40-g-cm-3 and 1.40-g-cm-3 subunits, are present in cell extracts. 35S label is bound to 1.37-g-cm-3 and 1.40-g-cm-s subunits when [35S]Met-tRANf, GTP and poly(A,U,G) are included in the incubations. The 35S-labelled 40-S subunits recovered, and the amount of 35S label bound to them, are changed if the [35S]Met-tRNAf-40-S-subunit-poly(A,U,G) complexes are first purified on sucrose gradients before analysing them on CsCl. The 1.37-g-cm-3 particle is no longer seen and the total quantity of 35S label on the 40-S subunits is 90% lower after sucrose gradient purification. Between 30% and 40% of the 40-S subunits bind [35S]Met-tRNAf when 1 mM GTP, an excess of ribosomal wash proteins and [35S]Met-tRNAf over derived 40-S subunits, and poly(A,U,G) or AUG is included in the incubations. The omission of poly(A,U,G) or AUG from the incubations substantially lowers the amount of subunit-bound 35S label ultimately recovered. With these incubations less than 10% of the 40-S subunits have bound [35S]Met-tRNAf. [35S]Met-tRNAf binding is affected by the nature of the RNA added. The addition of poly(U), rRNA and native 9-S golbin mRNA is without effect, whereas denatured globin mRNA is stimulatory. Maximum binding is obtained however with AUG. Poly(A,U,G) is less stimulatory than AUG but more stimulatory than denatured mRNA, suggesting that the number as well the accessibility of the AUG initiations condons determines the amount of 35S label bound. Similar results are obtained for the ribosomal-wash-dependent binding of [35S]Met-tRNAf to 80-S ribosomes. Contrary to the binding results, the ability of mRNA to stimulate protein synthesis is dependent on the integrity of the mRNA. Thus, native 9-S globin mRNA but not poly(A,U,G) stimulatex protein synthesis in the wheat germ system. HCHO-treated globin mRNA, although stimulatory, is 45% less effective than native mRNA. The addition of AUG, derived 60-S subunits and extra ribosomal wash is required for the formation of [35S]Met-tRNAf-80-S-ribosome complexes from sucrose-gradient-purified [35S]Met-tRNAf-40-S-subunit complexes. The 80-S ribosome complexes are able to form peptide bonds. Thus, if puromycin is added to the full incubations at zero time, no 35S label is present on the 80-S ribosome. 35S label is released as methionyl-puromycin. If the [35S]Met-tRNAf-40-S-subunit complexes are assembled with poly(A,U,G) or AUG in the incubations and then purified, only derived 60-S subunits are required to form [35S]Met-tRNAf-80-S-ribosome complexes. 35S label is not released from them when puromycin is added to the incubations unless extra ribosomal wash is also added.", "contents": "The binding of Met-tRNAf to isolated 40-S ribosomal subunits and the formation of Met-tRNAf - 80-S-ribosome initiation complexes. Different forms of 40-S ribosomal subunit, distinguishable by their buoyant densities on CsCl equilibrium density gradients, are formed when derived 40-S ribosomal subunits are incubated with partially purified reticulocyte ribosomal wash proteins. One of these subunits, the 1.37-g-cm-3 form is not present in the cell but the other two forms, the 1.40-g-cm-3 and 1.40-g-cm-3 subunits, are present in cell extracts. 35S label is bound to 1.37-g-cm-3 and 1.40-g-cm-s subunits when [35S]Met-tRANf, GTP and poly(A,U,G) are included in the incubations. The 35S-labelled 40-S subunits recovered, and the amount of 35S label bound to them, are changed if the [35S]Met-tRNAf-40-S-subunit-poly(A,U,G) complexes are first purified on sucrose gradients before analysing them on CsCl. The 1.37-g-cm-3 particle is no longer seen and the total quantity of 35S label on the 40-S subunits is 90% lower after sucrose gradient purification. Between 30% and 40% of the 40-S subunits bind [35S]Met-tRNAf when 1 mM GTP, an excess of ribosomal wash proteins and [35S]Met-tRNAf over derived 40-S subunits, and poly(A,U,G) or AUG is included in the incubations. The omission of poly(A,U,G) or AUG from the incubations substantially lowers the amount of subunit-bound 35S label ultimately recovered. With these incubations less than 10% of the 40-S subunits have bound [35S]Met-tRNAf. [35S]Met-tRNAf binding is affected by the nature of the RNA added. The addition of poly(U), rRNA and native 9-S golbin mRNA is without effect, whereas denatured globin mRNA is stimulatory. Maximum binding is obtained however with AUG. Poly(A,U,G) is less stimulatory than AUG but more stimulatory than denatured mRNA, suggesting that the number as well the accessibility of the AUG initiations condons determines the amount of 35S label bound. Similar results are obtained for the ribosomal-wash-dependent binding of [35S]Met-tRNAf to 80-S ribosomes. Contrary to the binding results, the ability of mRNA to stimulate protein synthesis is dependent on the integrity of the mRNA. Thus, native 9-S globin mRNA but not poly(A,U,G) stimulatex protein synthesis in the wheat germ system. HCHO-treated globin mRNA, although stimulatory, is 45% less effective than native mRNA. The addition of AUG, derived 60-S subunits and extra ribosomal wash is required for the formation of [35S]Met-tRNAf-80-S-ribosome complexes from sucrose-gradient-purified [35S]Met-tRNAf-40-S-subunit complexes. The 80-S ribosome complexes are able to form peptide bonds. Thus, if puromycin is added to the full incubations at zero time, no 35S label is present on the 80-S ribosome. 35S label is released as methionyl-puromycin. If the [35S]Met-tRNAf-40-S-subunit complexes are assembled with poly(A,U,G) or AUG in the incubations and then purified, only derived 60-S subunits are required to form [35S]Met-tRNAf-80-S-ribosome complexes. 35S label is not released from them when puromycin is added to the incubations unless extra ribosomal wash is also added."} {"id": "PMID:1253791", "title": "Binding of secretory component to dimers of immunoglobulin A in vitro. Mechanism of the covalent bond formation.", "content": "A complex between secretory component and an immunoglobulin A (IgA) myeloma dimer has been studied in vitro as a model to elucidate the mechanism of the formation of disulfide bonds during assembly in vivo of secretory immunoglobin A. A small amount of free thiol groups, totally about 0.4 groups per mole of protein, were shown to be present on both the heavy and light chains of the IgA dimer, but not on its J-chain, while no such groups could be demonstrated on free secretory component. The SH-groups on IgA most likely exist as a result of incomplete oxidation of some intra-or interchain disulfide bonds of the molecule, analogous to what has been suggested for IgG. Several types of evidence indicated that the disulfide bonds between secretory component and IgA are formed after the noncovalent association of the two proteins by a sulfhydryl group-disulfide bond exchange reaction, in which the small amount of free sulfhydryl groups on the IgA dimer initiate the reaction by reducing a reactive disulfide bond on secretory component. This exchange reaction, which thus proceeds by the mechanism of so-called disulfide interchange reactions, requires certain conformational features of one or both of the proteins and leads to the formation of presumably two new interchain disulfide bonds between secretory component and IgA. The reaction does not progress to completion, however, but ends in an equilibrium so that a small proportion of the secretory component molecules always are unattached by disulfide bonds.", "contents": "Binding of secretory component to dimers of immunoglobulin A in vitro. Mechanism of the covalent bond formation. A complex between secretory component and an immunoglobulin A (IgA) myeloma dimer has been studied in vitro as a model to elucidate the mechanism of the formation of disulfide bonds during assembly in vivo of secretory immunoglobin A. A small amount of free thiol groups, totally about 0.4 groups per mole of protein, were shown to be present on both the heavy and light chains of the IgA dimer, but not on its J-chain, while no such groups could be demonstrated on free secretory component. The SH-groups on IgA most likely exist as a result of incomplete oxidation of some intra-or interchain disulfide bonds of the molecule, analogous to what has been suggested for IgG. Several types of evidence indicated that the disulfide bonds between secretory component and IgA are formed after the noncovalent association of the two proteins by a sulfhydryl group-disulfide bond exchange reaction, in which the small amount of free sulfhydryl groups on the IgA dimer initiate the reaction by reducing a reactive disulfide bond on secretory component. This exchange reaction, which thus proceeds by the mechanism of so-called disulfide interchange reactions, requires certain conformational features of one or both of the proteins and leads to the formation of presumably two new interchain disulfide bonds between secretory component and IgA. The reaction does not progress to completion, however, but ends in an equilibrium so that a small proportion of the secretory component molecules always are unattached by disulfide bonds."} {"id": "PMID:1253792", "title": "Organization of vitellogenin polysomes, size of the mRNA and polyadenylate fragment.", "content": "A heavy polysome fraction containing vitellogenin mRNA was isolated from the liver of oestradiol-treated chicks. As determined by urea-polyacrylamide gel electrophoresis, the molecular weight of vitellogenin mRNA is about 2.5 x 10(6). The mRNA contains a polyadenylate segment of about 220 nucleotides at the 3' end. The remaining 7000 nucleotides are sufficient to code for a polypeptide of Mr about 270000. Combining 'run off' experiments of heavy polysomes in vitro together with radioimmunoprecipitation and polyacrylamide gel electrophoresis of the translation product, we concluded that vitellogenin mRNA is probably monocistronic and the 2.5 x 10(6)-Mr mRNA codes for two polypeptides, Mr 30000 and 240000. The largest polypeptide is, in our cell-free system and liver homogenate, readily cleaved into smaller peptides.", "contents": "Organization of vitellogenin polysomes, size of the mRNA and polyadenylate fragment. A heavy polysome fraction containing vitellogenin mRNA was isolated from the liver of oestradiol-treated chicks. As determined by urea-polyacrylamide gel electrophoresis, the molecular weight of vitellogenin mRNA is about 2.5 x 10(6). The mRNA contains a polyadenylate segment of about 220 nucleotides at the 3' end. The remaining 7000 nucleotides are sufficient to code for a polypeptide of Mr about 270000. Combining 'run off' experiments of heavy polysomes in vitro together with radioimmunoprecipitation and polyacrylamide gel electrophoresis of the translation product, we concluded that vitellogenin mRNA is probably monocistronic and the 2.5 x 10(6)-Mr mRNA codes for two polypeptides, Mr 30000 and 240000. The largest polypeptide is, in our cell-free system and liver homogenate, readily cleaved into smaller peptides."} {"id": "PMID:1253793", "title": "On the mechanism of amylose branching by potato Q-enzyme.", "content": "1. When potato Q-enzyme converts amylose into an amylopectin-like molecule, the action is by a random, endo-type transglycosylation of the substrate chains. 2. Inter-chain transfer takes place during the formation of the amylopectin branch linkage. This is seen in experiments in which radioactive label was transferred between substrates of disparate molecular weight. Intra-chain transfer, leading to the formation of a branch linkage, is not excluded by these experiments. 3. The minimum length of amylose chain that can act as an acceptor in the transglycosylation reaction, under the experimental conditions described, is greater than 40 glucose units. 4. The requirement of Q-enzyme for substrate chains at least 40 glucose units in length is interpreted as meaning that a stabilized secondary and tertiary structure must be established in the substrate before it can be utilized by Q-enzyme, and that the forces that provide such conformation are sufficiently strong only when the chains are longer than the minimum. Inter-chain transfer is seen as taking place by one of two mechanisms. The first involved the reaction of the enzyme with a chain that has a stabilized (helical?) conformation. An enzyme-donor chain intermediate is formed, that then reacts with an acceptor chain to complete the transglycosylation. The second mechanism envisages the substrate for the enzyme as being a complex formed between two chains (a double helix?). The enzyme encounters the complex and carries out an inter-chain transglycosylation reactions.", "contents": "On the mechanism of amylose branching by potato Q-enzyme. 1. When potato Q-enzyme converts amylose into an amylopectin-like molecule, the action is by a random, endo-type transglycosylation of the substrate chains. 2. Inter-chain transfer takes place during the formation of the amylopectin branch linkage. This is seen in experiments in which radioactive label was transferred between substrates of disparate molecular weight. Intra-chain transfer, leading to the formation of a branch linkage, is not excluded by these experiments. 3. The minimum length of amylose chain that can act as an acceptor in the transglycosylation reaction, under the experimental conditions described, is greater than 40 glucose units. 4. The requirement of Q-enzyme for substrate chains at least 40 glucose units in length is interpreted as meaning that a stabilized secondary and tertiary structure must be established in the substrate before it can be utilized by Q-enzyme, and that the forces that provide such conformation are sufficiently strong only when the chains are longer than the minimum. Inter-chain transfer is seen as taking place by one of two mechanisms. The first involved the reaction of the enzyme with a chain that has a stabilized (helical?) conformation. An enzyme-donor chain intermediate is formed, that then reacts with an acceptor chain to complete the transglycosylation. The second mechanism envisages the substrate for the enzyme as being a complex formed between two chains (a double helix?). The enzyme encounters the complex and carries out an inter-chain transglycosylation reactions."} {"id": "PMID:1253794", "title": "Molecular-weight determination of animal-cell RNA by electrophoresis in formamide under fully denaturing conditions on exponential polyacrylamide gels.", "content": "A method for electrophoretic analysis of RNA under fully denaturing conditions on exponential gradient polyacrylamide gels is described. Full denaturation, and strand separation of DNA - RNA hybrids and double-stranded RNA is obtained in dry formamide only if electrophoresis is carried out at 45 degrees and 55 degrees C, respectively. In such conditions, the effects of secondary structure of RNA, important in aqueous medium, are suppressed and a linear correlation is obtained between the logarithm of the molecular weight of an RNA and its final position in the gel over the entire molecular weight range of 10(4) - 10(7). Based on absolute molecular weight standards, obtained from sequenced rRNA of Escherichia coli and tRNA and extrapolating to higher molecular weights the size of animal cell was reexamined. Precursor tRNA from HeLa cells migrates according to a molecular weight of 4.1 x 10(6). Nascent precursor mRNA has molecular weights of up to 5 x 10(6) in the case of duck erythroblasts and of up to 10(7) in HeLa cells. This seems to represent the largest size of non-viral animal-cell RNA molecules.", "contents": "Molecular-weight determination of animal-cell RNA by electrophoresis in formamide under fully denaturing conditions on exponential polyacrylamide gels. A method for electrophoretic analysis of RNA under fully denaturing conditions on exponential gradient polyacrylamide gels is described. Full denaturation, and strand separation of DNA - RNA hybrids and double-stranded RNA is obtained in dry formamide only if electrophoresis is carried out at 45 degrees and 55 degrees C, respectively. In such conditions, the effects of secondary structure of RNA, important in aqueous medium, are suppressed and a linear correlation is obtained between the logarithm of the molecular weight of an RNA and its final position in the gel over the entire molecular weight range of 10(4) - 10(7). Based on absolute molecular weight standards, obtained from sequenced rRNA of Escherichia coli and tRNA and extrapolating to higher molecular weights the size of animal cell was reexamined. Precursor tRNA from HeLa cells migrates according to a molecular weight of 4.1 x 10(6). Nascent precursor mRNA has molecular weights of up to 5 x 10(6) in the case of duck erythroblasts and of up to 10(7) in HeLa cells. This seems to represent the largest size of non-viral animal-cell RNA molecules."} {"id": "PMID:1253795", "title": "Transcription of specific genes in isolated nuclei from HeLa cells in vitro.", "content": "Isolated HeLa cell nuclei were employed to catalyze the synthesis of RNA in vitro. In the presence of low concentrations of alpha-amanitin (1 mug/ml), used to suppress the formation heterogeneous nRNA, these nuclei synthesize RNA very efficiently for extended periods of time (at least 60 min) at an elongation rate of about seven nucleotides per second. The product, analyzed on sucrose density gradients and polyacrylamide gels was found to exist of two predominant size classes. Synthesis of the 45-S ribosomal precursor was completely resistant even to high concentrations of alpha-amanitin (150 mug/ml) and hence was catalyzed by enzyme A (or I). A limited degree of processing of the 45-S precursor occurred in vitro. In addition, a second RNA class of low molecular weight (4-8 S) was synthesized by HeLa cell nuclei in the presence of 1 mug/ml alpha-amanitin in vitro. Analysis on 8% polyacrylamide gels resolved the RNA into four distinct components. Their synthesis was resistant to low (1 mug/ml) but clearly sensitive to high (150 mug/ml) concentrations of alpha-amanitin. Consequently the synthesis of all these small-molecular-weight RNA species is catalyzed by RNA polymerase C (or III). For the assessment of the initiation frequency of the individual classes of RNA, a new technique was developed independent of labelling the 5' end of the RNA molecule with the gamma-phosphate of the initiating nucleotide. It employs the double labelling of an RNA molecule with two different isotopes added sequentially at different stages of completion of the chain. From the incorporation ratio of the two isotopes into a particular class of RNA, conclusions can be drawn concerning their initiation frequency. The results obtained have shown a high reinitiation frequency for the small-molecular-weight RNA species at all stages of the incubation reaction. In contrast, reinitiation of the 45-S precursor RNA occurs only to a limited extent in isolated HeLa cell nuclei in vitro.", "contents": "Transcription of specific genes in isolated nuclei from HeLa cells in vitro. Isolated HeLa cell nuclei were employed to catalyze the synthesis of RNA in vitro. In the presence of low concentrations of alpha-amanitin (1 mug/ml), used to suppress the formation heterogeneous nRNA, these nuclei synthesize RNA very efficiently for extended periods of time (at least 60 min) at an elongation rate of about seven nucleotides per second. The product, analyzed on sucrose density gradients and polyacrylamide gels was found to exist of two predominant size classes. Synthesis of the 45-S ribosomal precursor was completely resistant even to high concentrations of alpha-amanitin (150 mug/ml) and hence was catalyzed by enzyme A (or I). A limited degree of processing of the 45-S precursor occurred in vitro. In addition, a second RNA class of low molecular weight (4-8 S) was synthesized by HeLa cell nuclei in the presence of 1 mug/ml alpha-amanitin in vitro. Analysis on 8% polyacrylamide gels resolved the RNA into four distinct components. Their synthesis was resistant to low (1 mug/ml) but clearly sensitive to high (150 mug/ml) concentrations of alpha-amanitin. Consequently the synthesis of all these small-molecular-weight RNA species is catalyzed by RNA polymerase C (or III). For the assessment of the initiation frequency of the individual classes of RNA, a new technique was developed independent of labelling the 5' end of the RNA molecule with the gamma-phosphate of the initiating nucleotide. It employs the double labelling of an RNA molecule with two different isotopes added sequentially at different stages of completion of the chain. From the incorporation ratio of the two isotopes into a particular class of RNA, conclusions can be drawn concerning their initiation frequency. The results obtained have shown a high reinitiation frequency for the small-molecular-weight RNA species at all stages of the incubation reaction. In contrast, reinitiation of the 45-S precursor RNA occurs only to a limited extent in isolated HeLa cell nuclei in vitro."} {"id": "PMID:1253796", "title": "Comparison of cytoplasmic and nuclear poly(A)-containing RNA sequences in Xenopus liver cells.", "content": "Poly(A)-containing RNAs from cytoplasm and nuclei of adult Xenopus liver cells are compared. After denaturation of the RNA by dimethysulfoxide the average molecule of nuclear poly(A)-containing RNA has a sedimentation value of 28 S whereas the cytoplasmic poly(A)-containing RNA sediments slightly ahead of 18 S. To compare the complexity of cytoplasmic and nuclear poly(A)-containing RNA, complementary DNA (cDNA) transcribed on either cytoplasmic or nuclear RNA is hybridized to the RNA used as a template. The hybridization kinetics suggest a higher complexity of the nuclear RNA compared to the cytoplasmic fraction. Direct evidence of a higher complexity of nuclear poly(A)-containing RNA is shown by the fact that 30% of the nuclear cDNA fails to hybridize with cytoplasmic poly(A)-containing RNA. An attempt to isolate a specific probe for this nucleus-restricted poly(A)-containing RNA reveals that more than 10(4) different nuclear RNA sequences adjacent to the poly(A) do not get into the cytoplasm. We conclude that a poly(A) on a nuclear RNA does not ensure the transport of the adjacent sequence to the cytoplasm.", "contents": "Comparison of cytoplasmic and nuclear poly(A)-containing RNA sequences in Xenopus liver cells. Poly(A)-containing RNAs from cytoplasm and nuclei of adult Xenopus liver cells are compared. After denaturation of the RNA by dimethysulfoxide the average molecule of nuclear poly(A)-containing RNA has a sedimentation value of 28 S whereas the cytoplasmic poly(A)-containing RNA sediments slightly ahead of 18 S. To compare the complexity of cytoplasmic and nuclear poly(A)-containing RNA, complementary DNA (cDNA) transcribed on either cytoplasmic or nuclear RNA is hybridized to the RNA used as a template. The hybridization kinetics suggest a higher complexity of the nuclear RNA compared to the cytoplasmic fraction. Direct evidence of a higher complexity of nuclear poly(A)-containing RNA is shown by the fact that 30% of the nuclear cDNA fails to hybridize with cytoplasmic poly(A)-containing RNA. An attempt to isolate a specific probe for this nucleus-restricted poly(A)-containing RNA reveals that more than 10(4) different nuclear RNA sequences adjacent to the poly(A) do not get into the cytoplasm. We conclude that a poly(A) on a nuclear RNA does not ensure the transport of the adjacent sequence to the cytoplasm."} {"id": "PMID:1253797", "title": "EEG spectral analysis in children with febrile convulsions.", "content": "The abnormal theta-rhythm of the EEG can be identified by use of spectral analysis. The rhythms appear as peaks in the power spectrum and can be considered as given, if the intensity of this peak is significantly higher than the average intensity and if a left-right coherence is present. Abnormal theta-rhythms in the parietal region are significantly more frequent in children with a histroy of febrile convulsions than in controls. This difference becomes especially obvious in the records with open eyes. According to previous investigations, the abnormal theta-rhythm is correlated with a genetically determined susceptibility to convulsions.", "contents": "EEG spectral analysis in children with febrile convulsions. The abnormal theta-rhythm of the EEG can be identified by use of spectral analysis. The rhythms appear as peaks in the power spectrum and can be considered as given, if the intensity of this peak is significantly higher than the average intensity and if a left-right coherence is present. Abnormal theta-rhythms in the parietal region are significantly more frequent in children with a histroy of febrile convulsions than in controls. This difference becomes especially obvious in the records with open eyes. According to previous investigations, the abnormal theta-rhythm is correlated with a genetically determined susceptibility to convulsions."} {"id": "PMID:1253798", "title": "Visual evoked responses and their dispersion pattern in frontal lobe tumours.", "content": "In patients with frontal lobe tumours the averaged visual evoked responses (AVER) and their dispersion pattern (DP) in visual areas were investigated before and at different periods after operation. Important changes in AVER (in amplitude and latency) were found in the patients with tumours on the midline or in one of the frontal lobes. The DP was abnormal in all the cases. There was no relation to visual acuity, tumour location and existance of intracranial hypertension. After operation, despite the clinical improvement, the alterations of AVERs or DPs were very marked and in some cases became even more important than before. The role of the frontal lobe in the organization of the responses to peripheral stimuli in the visual areas is discussed.", "contents": "Visual evoked responses and their dispersion pattern in frontal lobe tumours. In patients with frontal lobe tumours the averaged visual evoked responses (AVER) and their dispersion pattern (DP) in visual areas were investigated before and at different periods after operation. Important changes in AVER (in amplitude and latency) were found in the patients with tumours on the midline or in one of the frontal lobes. The DP was abnormal in all the cases. There was no relation to visual acuity, tumour location and existance of intracranial hypertension. After operation, despite the clinical improvement, the alterations of AVERs or DPs were very marked and in some cases became even more important than before. The role of the frontal lobe in the organization of the responses to peripheral stimuli in the visual areas is discussed."} {"id": "PMID:1253799", "title": "Encephalopathy subsequent to accidental poisoning with chlorpromazine.", "content": "A cerebral biopsy performed in an infant 9 months after accidental poisoning with chlorpromazine was studied. Light microscopy disclosed necrosing encephalopathy, while electron microscopy showed neuronal, glial, myelinic and vascular lesions. The findings in the present study suggest that the various neurologic syndromes appearing in cases of prolonged treatment with neuroleptic drugs and persisting after cessation of therapy would be due to consequent occurrence, in specific areas, of some irreversible cerebral lesions.", "contents": "Encephalopathy subsequent to accidental poisoning with chlorpromazine. A cerebral biopsy performed in an infant 9 months after accidental poisoning with chlorpromazine was studied. Light microscopy disclosed necrosing encephalopathy, while electron microscopy showed neuronal, glial, myelinic and vascular lesions. The findings in the present study suggest that the various neurologic syndromes appearing in cases of prolonged treatment with neuroleptic drugs and persisting after cessation of therapy would be due to consequent occurrence, in specific areas, of some irreversible cerebral lesions."} {"id": "PMID:1253800", "title": "Occult normal pressure hydrocephalus with parkinsonian symptomatology.", "content": "The authors describe a case where a parkinsonian symptomatology is associated with pneumoencephalographic and RISA-cisternographic findings typical of an occult normal pressure hydrocephalus. They discuss their personal contribution in the light of what has been already reported in the literature on the same subject. They conclude that a CSF dynamics disturbance among the possible physiopathogenetic mechanisms of an extrapyramidal syndrome in young subjects should be considered. On the other hand, they also emphasize the possibility that the occult normal pressure hydrocephalus may have syndromical expression which are different from the typical one initially described.", "contents": "Occult normal pressure hydrocephalus with parkinsonian symptomatology. The authors describe a case where a parkinsonian symptomatology is associated with pneumoencephalographic and RISA-cisternographic findings typical of an occult normal pressure hydrocephalus. They discuss their personal contribution in the light of what has been already reported in the literature on the same subject. They conclude that a CSF dynamics disturbance among the possible physiopathogenetic mechanisms of an extrapyramidal syndrome in young subjects should be considered. On the other hand, they also emphasize the possibility that the occult normal pressure hydrocephalus may have syndromical expression which are different from the typical one initially described."} {"id": "PMID:1253801", "title": "Measurement of jugular venous blood gases for prediction of brain ischaemia following carotid ligation. A comparison with direct measurements of cerebral blood flow.", "content": "Measurements of various indices derived from arterial and jugular venous blood gas and pH values during temporary carotid clamping have been compared with measurements of cerebral blood flow and internal carotid artery pressure in 15 patients referred for carotid ligation. Cerebral venous blood gas measurements did not provide a reliable index of cerebral ischaemia.", "contents": "Measurement of jugular venous blood gases for prediction of brain ischaemia following carotid ligation. A comparison with direct measurements of cerebral blood flow. Measurements of various indices derived from arterial and jugular venous blood gas and pH values during temporary carotid clamping have been compared with measurements of cerebral blood flow and internal carotid artery pressure in 15 patients referred for carotid ligation. Cerebral venous blood gas measurements did not provide a reliable index of cerebral ischaemia."} {"id": "PMID:1253802", "title": "A reappraisal of the significance of thymic germinal centers in myasthenia gravis.", "content": "The morphology of thymuses removed from 16 cases of myasthenia gravis was studied in an attempt to correlate clinical response following thymectomy with the frequency of thymic germinal centers. In these patients, the presence of germinal centers in the thymus did not appear to influence response to thymectomy.", "contents": "A reappraisal of the significance of thymic germinal centers in myasthenia gravis. The morphology of thymuses removed from 16 cases of myasthenia gravis was studied in an attempt to correlate clinical response following thymectomy with the frequency of thymic germinal centers. In these patients, the presence of germinal centers in the thymus did not appear to influence response to thymectomy."} {"id": "PMID:1253803", "title": "Results of electromyographical and electroneurographical investigations concerning syringomyelia.", "content": "16 patients suffering from syringomyelia were checked for additional peripheral nerve lesions. On voluntary effort, often in conformity with the decrease of muscle strength, a moderate rarefication of the discharge patterns was apparent. Fasciculation potentials were common. Motor conduction velocities of the median and ulnar nerve were in the normal range in cases without additional peripheral nervous lesion at the elbow or the carpal. Depending on the severity of the peripheral nervous lesion, we found the duration of the muscle action potentials increased.", "contents": "Results of electromyographical and electroneurographical investigations concerning syringomyelia. 16 patients suffering from syringomyelia were checked for additional peripheral nerve lesions. On voluntary effort, often in conformity with the decrease of muscle strength, a moderate rarefication of the discharge patterns was apparent. Fasciculation potentials were common. Motor conduction velocities of the median and ulnar nerve were in the normal range in cases without additional peripheral nervous lesion at the elbow or the carpal. Depending on the severity of the peripheral nervous lesion, we found the duration of the muscle action potentials increased."} {"id": "PMID:1253804", "title": "Liver function and gastric acid secretion in parkinsonian patients under prolonged treatment with L-dopa and a peripheral decarboxylase inhibitor.", "content": "Twelve patients with long-standing Parkinson's disease, treated successfully with a combination of l-dopa and an inhibitor of aromatic l-amino acid decarboxylase (Ro 4-4602), in the ratio 4:1, were screened for damage to various organ systems, in particular liver and skeleton. Among other tests, liver biopsies were obtained before and after 6 months of treatment. One patient discontinued therapy becuase of an accentuation of pre-existent liver damage, another because of psychomental manifestations. The remaining ten patients were followed for 8-15 months and longer. The liver biopsies remained practically unaltered. Elevation of alkaline phosphatase was found in 10 out of 12 subjects. In five patients this rise fluctuated around the upper limit of normal. In two patients, who discontinued the treatment, the raised alkaline phosphatase values soon returned to normal. Analysis of isozymes proved this phosphatase to be of liver origin. All other liver function tests remained unchanged, except for an increased retention of bromsulphalein in two patients. In the one patient with the initially damaged liver, all tests became normal soon after discontinuation of therapy. No changes could be found in gastric acid secretion. All other parameters studied remained within normal limits, including urinary excretion of calcium and phosphate.", "contents": "Liver function and gastric acid secretion in parkinsonian patients under prolonged treatment with L-dopa and a peripheral decarboxylase inhibitor. Twelve patients with long-standing Parkinson's disease, treated successfully with a combination of l-dopa and an inhibitor of aromatic l-amino acid decarboxylase (Ro 4-4602), in the ratio 4:1, were screened for damage to various organ systems, in particular liver and skeleton. Among other tests, liver biopsies were obtained before and after 6 months of treatment. One patient discontinued therapy becuase of an accentuation of pre-existent liver damage, another because of psychomental manifestations. The remaining ten patients were followed for 8-15 months and longer. The liver biopsies remained practically unaltered. Elevation of alkaline phosphatase was found in 10 out of 12 subjects. In five patients this rise fluctuated around the upper limit of normal. In two patients, who discontinued the treatment, the raised alkaline phosphatase values soon returned to normal. Analysis of isozymes proved this phosphatase to be of liver origin. All other liver function tests remained unchanged, except for an increased retention of bromsulphalein in two patients. In the one patient with the initially damaged liver, all tests became normal soon after discontinuation of therapy. No changes could be found in gastric acid secretion. All other parameters studied remained within normal limits, including urinary excretion of calcium and phosphate."} {"id": "PMID:1253806", "title": "The effect of spironolactone on transport of Na+, K+ and H+. A microperfusion study in rat main submaxillary duct.", "content": "The epithelium of the main excretory duct of the rat submaxillary gland was used as a target tissue for studies on the effect of a spironolactone on electrolyte transport. The spironolactone decreased net Na+ reabsorption by 27% and net K+ secretion by 23%. HCO-3 was found to be about 2-fold accumulated in the duct lumen, which was considered to result from decreased H+ion secretion. The results can be reconciled with an action of spironolactone on 1) the peritubular Na+-K+-exchange mechanism and 2) the functional coupling of Na+ entry from lumen to cell with K+ and H+ transfer from cell to lumen.", "contents": "The effect of spironolactone on transport of Na+, K+ and H+. A microperfusion study in rat main submaxillary duct. The epithelium of the main excretory duct of the rat submaxillary gland was used as a target tissue for studies on the effect of a spironolactone on electrolyte transport. The spironolactone decreased net Na+ reabsorption by 27% and net K+ secretion by 23%. HCO-3 was found to be about 2-fold accumulated in the duct lumen, which was considered to result from decreased H+ion secretion. The results can be reconciled with an action of spironolactone on 1) the peritubular Na+-K+-exchange mechanism and 2) the functional coupling of Na+ entry from lumen to cell with K+ and H+ transfer from cell to lumen."} {"id": "PMID:1253807", "title": "Phenazone metabolism in patients with liver disease.", "content": "Phenazone metabolism was studied in 14 patients with liver disease and six normal volunteers. The plasma and renal clearance of phenazone and the 4-hydrozyphenazone excretion in urine was significantly decreased in the patients with liver disease. The urinary excretion of 4-hydroxyphenazone was significantly correlated to the plasma clearance of phenazone (r= + 0.95, P less than 0.001), to quantitative liver function as measured by the galactose elimination capacity (r= + 0.95, P less than 0.001), and to the prothrombin values (r= + 0.82, P less than 0.001). The determination of the 4-hydroxyphenazone excretion in urine may be used as an easy and non-invasive test of quantitative liver function.", "contents": "Phenazone metabolism in patients with liver disease. Phenazone metabolism was studied in 14 patients with liver disease and six normal volunteers. The plasma and renal clearance of phenazone and the 4-hydrozyphenazone excretion in urine was significantly decreased in the patients with liver disease. The urinary excretion of 4-hydroxyphenazone was significantly correlated to the plasma clearance of phenazone (r= + 0.95, P less than 0.001), to quantitative liver function as measured by the galactose elimination capacity (r= + 0.95, P less than 0.001), and to the prothrombin values (r= + 0.82, P less than 0.001). The determination of the 4-hydroxyphenazone excretion in urine may be used as an easy and non-invasive test of quantitative liver function."} {"id": "PMID:1253808", "title": "Diabetes mellitus in gonadal dysgenesis: studies of insulin and growth hormone secretion.", "content": "On the basis of results obtained from an oral glucose tolerance test, (OGTT), twenty patients with gonadal dysgenesis were classified as normal (N = 8) and diabetic (N = 12). The two groups of patients were further tested by a rapid intravenous glucose injection, a tolbutamide test, an insulin sensitivity test and an oral amino acid load. Fasting levels of plasma growth hormone (GH) were normal in all subjects but one. Approximately 1/3 of the GH responses during testing periods were abnormal, being either absent during hypoglycaemia or following amino acid ingestion, or paradoxically increased during hyperglycaemia. No correlation was found between the degree of carbohydrate intolerance and the levels of plasma GH. There was no gross alteration of tissue sensitivity to exogenous insulin. The beta-cell response to tolbutamide, amino acid and intravenous glucose were comparable in patients with a normal or a diabetic OGTT. In both groups, the rates of decrease of blood glucose following tolbutamide or intravenous glucose were also similar and within the normal range. During OGTT, the diabetic group had a delayed insulin release and a low insulinogenic index. It is concluded that in gonadal dysgenesis the intolerance to an oral carbohydrate load is frequently associated with, but unrelated to, anomalies of the GH secretion. In diabetic subjects, the process of insulin secretion loses its normal sensitivity to the oral glucose stimulus while remaining unaltered and similiar to that of non-diabetic subjects in response to tolbutamide, amino acid and intravenous glucose.", "contents": "Diabetes mellitus in gonadal dysgenesis: studies of insulin and growth hormone secretion. On the basis of results obtained from an oral glucose tolerance test, (OGTT), twenty patients with gonadal dysgenesis were classified as normal (N = 8) and diabetic (N = 12). The two groups of patients were further tested by a rapid intravenous glucose injection, a tolbutamide test, an insulin sensitivity test and an oral amino acid load. Fasting levels of plasma growth hormone (GH) were normal in all subjects but one. Approximately 1/3 of the GH responses during testing periods were abnormal, being either absent during hypoglycaemia or following amino acid ingestion, or paradoxically increased during hyperglycaemia. No correlation was found between the degree of carbohydrate intolerance and the levels of plasma GH. There was no gross alteration of tissue sensitivity to exogenous insulin. The beta-cell response to tolbutamide, amino acid and intravenous glucose were comparable in patients with a normal or a diabetic OGTT. In both groups, the rates of decrease of blood glucose following tolbutamide or intravenous glucose were also similar and within the normal range. During OGTT, the diabetic group had a delayed insulin release and a low insulinogenic index. It is concluded that in gonadal dysgenesis the intolerance to an oral carbohydrate load is frequently associated with, but unrelated to, anomalies of the GH secretion. In diabetic subjects, the process of insulin secretion loses its normal sensitivity to the oral glucose stimulus while remaining unaltered and similiar to that of non-diabetic subjects in response to tolbutamide, amino acid and intravenous glucose."} {"id": "PMID:1253809", "title": "Bile salt glucuronides: identification and quantitative analysis in the urine of patients with cholestasis.", "content": "Glucuronides of lithocholate, chenodeoxycholate and cholate were synthesized enzymatically and characterized by thin layer chromatography, column chromatography and specific enzymatic hydrolysis. Bile salt glucuronides were quantitatively analysed in thr urine of patients with intra- and extra- hepatic cholestasis and were found to be present in 19 out of 20 patients studied. Our patients with intrahepatic cholestasis excreted 8.9 mg non-sulphated and non-glucoronidated bile salts, 18.2 mg sulphated bile salts and 7.2 mg glucuronidated bile salts. The patients with extrahepatic cholestasis excreted 14.7 mg non-sulphated and non-glucuronidated bile salts, 20.7 mg sulphated bile salts and 4.7 mg glucuronidated bile salts. These findings indicate that glucuronidation of bile salts occurs in man and represents a metabolic pathway in patients with cholestasis.", "contents": "Bile salt glucuronides: identification and quantitative analysis in the urine of patients with cholestasis. Glucuronides of lithocholate, chenodeoxycholate and cholate were synthesized enzymatically and characterized by thin layer chromatography, column chromatography and specific enzymatic hydrolysis. Bile salt glucuronides were quantitatively analysed in thr urine of patients with intra- and extra- hepatic cholestasis and were found to be present in 19 out of 20 patients studied. Our patients with intrahepatic cholestasis excreted 8.9 mg non-sulphated and non-glucoronidated bile salts, 18.2 mg sulphated bile salts and 7.2 mg glucuronidated bile salts. The patients with extrahepatic cholestasis excreted 14.7 mg non-sulphated and non-glucuronidated bile salts, 20.7 mg sulphated bile salts and 4.7 mg glucuronidated bile salts. These findings indicate that glucuronidation of bile salts occurs in man and represents a metabolic pathway in patients with cholestasis."} {"id": "PMID:1253810", "title": "Effects of myocardial revascularization following acute coronary occlusion in pigs.", "content": "In a comparative study in pigs the extent of myocardial infarction has been estimated following a temporary three hour coronary occlusion and following a permanent coronary ligation. For evaluation of the cellular injury the infarct size has been determined by a histochemical staining procedure and correlated with serum enzyme studies (creatine phosphokinase, alpha-hydroxybutyric dehydrogenase) in the surviving animal. No significant difference could be detected between the two experimental groups and the extent of cellular damage was similar. A strict linear correlation was found between the serum enzyme activity plotted logarithmically and the morphological infarct size. Likewise the incidence of ventricular fibrillation depended on the extent of cellular injury. Myocardial revascularization does not appear to benefit a pig heart subjected to an acute coronary occlusion lasting three hours or more. Revascularization may even be harmful by creating a haemorrhagic infarct, as found in all the animals submitted to a transient coronary occlusion.", "contents": "Effects of myocardial revascularization following acute coronary occlusion in pigs. In a comparative study in pigs the extent of myocardial infarction has been estimated following a temporary three hour coronary occlusion and following a permanent coronary ligation. For evaluation of the cellular injury the infarct size has been determined by a histochemical staining procedure and correlated with serum enzyme studies (creatine phosphokinase, alpha-hydroxybutyric dehydrogenase) in the surviving animal. No significant difference could be detected between the two experimental groups and the extent of cellular damage was similar. A strict linear correlation was found between the serum enzyme activity plotted logarithmically and the morphological infarct size. Likewise the incidence of ventricular fibrillation depended on the extent of cellular injury. Myocardial revascularization does not appear to benefit a pig heart subjected to an acute coronary occlusion lasting three hours or more. Revascularization may even be harmful by creating a haemorrhagic infarct, as found in all the animals submitted to a transient coronary occlusion."} {"id": "PMID:1253811", "title": "Sodium balance and renal tubular sensitivity to aldosterone during total fast and carbohydrate refeeding in the obese.", "content": "In man the first days of fasting are characterized by enhanced natriuresis despite an increase in aldosterone secretion. Therefore the possibility of a decreased renal tubular sensitivity to this hormone was considered. The response to aldosterone infused before a fast and again on day 4 of fasting was evaluated in 12 starving obese women in terms of urinary sodium, chloride and potassium excretion. The data were compared to those obtained from 20 untreated starving obese women. In addition, salivary flow and sodium output were measured before and after aldosterone infusion in 4 out of the 12 patients treated. The involvement of aldosterone in the mechanism of fasting natriuresis and glucose-induced sodium retention was evaluated by means of spironolactone treatment (Aldactone A; 300 mg/day p.o.) on days 6 to 8 of the fast, with an oral glucose load (100 g) on day 7. Aldosterone infused on day 4 of the fast caused on average only 40% of the antinatriuretic effect it achieved before the fast. On the other hand even before aldosterone infusion, salivary sodium output was markedly reduced during the fast to levels comparable to those observed after aldosterone treatment in the pre-fast period. Furthermore, spironolactone administration on day 6 of the fast was associated with a prompt and marked increase in natriuresis. These 3 sets of facts indicate a definite biological activity of aldosterone during the initial phase of fasting with factor(s) interfering at the renal level with the normal expression of the hormonal action on sodium balance. There was still a distinct antinatiuretic effect of glucose in the presence of spironolactone, but less pronounced than when glucose was administered alone. The well-documented hyperaldosteronism of a total fast may represent a compensatory mechanism to decrease sodium loss at the end of a week-long fast. In addition a marked sodium-retaining effect of glucose can be demonstrated after aldosterone action is blocked by spironolactone. This provides another indication that glucose stimulates sodium retention through mechanism(s) which do not involve aldosterone.", "contents": "Sodium balance and renal tubular sensitivity to aldosterone during total fast and carbohydrate refeeding in the obese. In man the first days of fasting are characterized by enhanced natriuresis despite an increase in aldosterone secretion. Therefore the possibility of a decreased renal tubular sensitivity to this hormone was considered. The response to aldosterone infused before a fast and again on day 4 of fasting was evaluated in 12 starving obese women in terms of urinary sodium, chloride and potassium excretion. The data were compared to those obtained from 20 untreated starving obese women. In addition, salivary flow and sodium output were measured before and after aldosterone infusion in 4 out of the 12 patients treated. The involvement of aldosterone in the mechanism of fasting natriuresis and glucose-induced sodium retention was evaluated by means of spironolactone treatment (Aldactone A; 300 mg/day p.o.) on days 6 to 8 of the fast, with an oral glucose load (100 g) on day 7. Aldosterone infused on day 4 of the fast caused on average only 40% of the antinatriuretic effect it achieved before the fast. On the other hand even before aldosterone infusion, salivary sodium output was markedly reduced during the fast to levels comparable to those observed after aldosterone treatment in the pre-fast period. Furthermore, spironolactone administration on day 6 of the fast was associated with a prompt and marked increase in natriuresis. These 3 sets of facts indicate a definite biological activity of aldosterone during the initial phase of fasting with factor(s) interfering at the renal level with the normal expression of the hormonal action on sodium balance. There was still a distinct antinatiuretic effect of glucose in the presence of spironolactone, but less pronounced than when glucose was administered alone. The well-documented hyperaldosteronism of a total fast may represent a compensatory mechanism to decrease sodium loss at the end of a week-long fast. In addition a marked sodium-retaining effect of glucose can be demonstrated after aldosterone action is blocked by spironolactone. This provides another indication that glucose stimulates sodium retention through mechanism(s) which do not involve aldosterone."} {"id": "PMID:1253812", "title": "Effects of fructose and glucose on ethanol-induced metabolic changes and on the intensity of alcohol intoxication and hangover.", "content": "The effects of fructose and glucose on the metabolic changes induced by ethanol and on the intensity of alcohol intoxication and hangover were studied in 109 healthy male volunteers. After 10 hours of fasting, the subjects were given 1.75 g of ethanol per kg body wt during 3 hours under controlled laboratory conditions. Fructose or glucose were adminstered either simultaneously with ethanol or 12 hours later during the hangover period. The intensity of alcohol intoxication and hangover were estimated 10 times during the experimental period of 20 hours using subjective and objective rating scales. Sequential determinations of blood ethanol, acetaldehyde, glucose, lactate, free fatty acids, triglycerides, ketone bodies and capillary blood acid-base balance were also made during the experiment. Under these experimental conditions neither fructose nor glucose had any significant effect on the intensity of alcohol intoxication and hangover. The sugars also had no significant effect on the rate of ethanol elimination or on the blood acetaldehyde concentration during the course of the experiment. Blood glucose concentration was decreased and blood lactate, free fatty acid and ketone body concentrations were increased during the hangover period in the subjects who had been given only ethanol. These subjects also had a marked metabolic acidosis during hangover. Glucose and fructose significantly inhibited the metabolic alterations induced by ethanol. In this respect fructose was more effective than glucose. The results indicate that both fructose and glucose effectively inhibit the metabolic disturbances induced by ethanol but they do not affect the symptoms or signs of alcohol intoxication and hangover. The results support the view that hangover is not directly related to the metabolic effects of ethanol or to its metabolic products.", "contents": "Effects of fructose and glucose on ethanol-induced metabolic changes and on the intensity of alcohol intoxication and hangover. The effects of fructose and glucose on the metabolic changes induced by ethanol and on the intensity of alcohol intoxication and hangover were studied in 109 healthy male volunteers. After 10 hours of fasting, the subjects were given 1.75 g of ethanol per kg body wt during 3 hours under controlled laboratory conditions. Fructose or glucose were adminstered either simultaneously with ethanol or 12 hours later during the hangover period. The intensity of alcohol intoxication and hangover were estimated 10 times during the experimental period of 20 hours using subjective and objective rating scales. Sequential determinations of blood ethanol, acetaldehyde, glucose, lactate, free fatty acids, triglycerides, ketone bodies and capillary blood acid-base balance were also made during the experiment. Under these experimental conditions neither fructose nor glucose had any significant effect on the intensity of alcohol intoxication and hangover. The sugars also had no significant effect on the rate of ethanol elimination or on the blood acetaldehyde concentration during the course of the experiment. Blood glucose concentration was decreased and blood lactate, free fatty acid and ketone body concentrations were increased during the hangover period in the subjects who had been given only ethanol. These subjects also had a marked metabolic acidosis during hangover. Glucose and fructose significantly inhibited the metabolic alterations induced by ethanol. In this respect fructose was more effective than glucose. The results indicate that both fructose and glucose effectively inhibit the metabolic disturbances induced by ethanol but they do not affect the symptoms or signs of alcohol intoxication and hangover. The results support the view that hangover is not directly related to the metabolic effects of ethanol or to its metabolic products."} {"id": "PMID:1253813", "title": "The importance of 5-hydroxytryptamine for the induction of harmine tremor and its antagonism by dopaminergic agonists assessed by lesions of the midbrain raphe nuclei.", "content": "The brain lesion technique was used to destroy the ascending 5-hydroxytryptamine (5-HT) system at its cell bodies in the dorsal and medial raphe nuclei in order to assess the importance of 5-HT for the induction of harmine tremor and its antagonism by the dopaminergic agonists, L-DOPA, apomorphine and d-amphetamine. Lesions of the medial or dorsal raphe nucleus reduced the intensity of harmine tremor. The remaining tremor was generally resistant to further reduction by the dopaminergic agonists. 5-hydroxytryptophan was shown to enhance tremor: this effect was reduced both by the raphe lesions and by treatment with L-DOPA. The data are discussed in terms of the possible relationship between 5-HT and dopamine.", "contents": "The importance of 5-hydroxytryptamine for the induction of harmine tremor and its antagonism by dopaminergic agonists assessed by lesions of the midbrain raphe nuclei. The brain lesion technique was used to destroy the ascending 5-hydroxytryptamine (5-HT) system at its cell bodies in the dorsal and medial raphe nuclei in order to assess the importance of 5-HT for the induction of harmine tremor and its antagonism by the dopaminergic agonists, L-DOPA, apomorphine and d-amphetamine. Lesions of the medial or dorsal raphe nucleus reduced the intensity of harmine tremor. The remaining tremor was generally resistant to further reduction by the dopaminergic agonists. 5-hydroxytryptophan was shown to enhance tremor: this effect was reduced both by the raphe lesions and by treatment with L-DOPA. The data are discussed in terms of the possible relationship between 5-HT and dopamine."} {"id": "PMID:1253814", "title": "Photoaffinity labeling of the beta-adrenergic receptors and receptor reserve for isoprenaline.", "content": "The beta-adrenergic receptors in the taenia isolated from the guinea pig caecum were irreversibly inactivated by photoaffinity labeling with 1-isoprenaline and 2-(2-hydroxy-3-isopropylaminopropoxy)iodobenzene. The photoinactivation was eliminated in the presence of protectors of the receptors. Photoinactivation caused a considerable parallel shift in the concentration-action curve of 1-isoprenaline. The results possibly point to a certain receptor reserve for 1-isoprenaline.", "contents": "Photoaffinity labeling of the beta-adrenergic receptors and receptor reserve for isoprenaline. The beta-adrenergic receptors in the taenia isolated from the guinea pig caecum were irreversibly inactivated by photoaffinity labeling with 1-isoprenaline and 2-(2-hydroxy-3-isopropylaminopropoxy)iodobenzene. The photoinactivation was eliminated in the presence of protectors of the receptors. Photoinactivation caused a considerable parallel shift in the concentration-action curve of 1-isoprenaline. The results possibly point to a certain receptor reserve for 1-isoprenaline."} {"id": "PMID:1253815", "title": "Modification of the L-DOPA reversal of reserpine akinesia by inhibitors of dopamine-beta-hydroxylase.", "content": "The effect of the dopamine-beta-hydroxylase inhibitors (DBHI) FLA-63 and U10,157 on the reversal of reserpine akinesia by L-DOPA in mice was investigated both behaviourally and by measurement of the cerebral amines dopamine and noradrenaline. Pretreatment of reserpinised animals with intraperitoneal, but not oral, FLA-63 produced hypermotility in the first hour after L-DOPA administration, compared to animals receiving L-DOPA alone. This enhanced activity was associated with an increase in dopamine, but no significant change in the noradrenaline content of whole brain. Pretreatment with both oral and intraperitoneal FLA-63 caused dose-dependent suppression of locomotor activity in the second and third hours after L-DOPA. This suppression was associated with a significant decrease in brain noradrenaline in the presence of a significant elevation in brain dopamine. Pretreatment of animals with U10,157 produced similar but less marked behavioural responses. The results do not appear to be due to stressful effects of DBHI's, causing release of corticosteroids; neither corticosterone nor beta-methasone had any significant effect on L-DOPA-induced locomotor activity in reserpinised animals, although they did increase spontaneous motor activity in normal animals. The data presented support the concept that both noradrenaline and dopamine are responsible for the gross motor activity induced by L-DOPA in the reserpinised mouse.", "contents": "Modification of the L-DOPA reversal of reserpine akinesia by inhibitors of dopamine-beta-hydroxylase. The effect of the dopamine-beta-hydroxylase inhibitors (DBHI) FLA-63 and U10,157 on the reversal of reserpine akinesia by L-DOPA in mice was investigated both behaviourally and by measurement of the cerebral amines dopamine and noradrenaline. Pretreatment of reserpinised animals with intraperitoneal, but not oral, FLA-63 produced hypermotility in the first hour after L-DOPA administration, compared to animals receiving L-DOPA alone. This enhanced activity was associated with an increase in dopamine, but no significant change in the noradrenaline content of whole brain. Pretreatment with both oral and intraperitoneal FLA-63 caused dose-dependent suppression of locomotor activity in the second and third hours after L-DOPA. This suppression was associated with a significant decrease in brain noradrenaline in the presence of a significant elevation in brain dopamine. Pretreatment of animals with U10,157 produced similar but less marked behavioural responses. The results do not appear to be due to stressful effects of DBHI's, causing release of corticosteroids; neither corticosterone nor beta-methasone had any significant effect on L-DOPA-induced locomotor activity in reserpinised animals, although they did increase spontaneous motor activity in normal animals. The data presented support the concept that both noradrenaline and dopamine are responsible for the gross motor activity induced by L-DOPA in the reserpinised mouse."} {"id": "PMID:1253816", "title": "Regional differences in the response to nicotine in isolated canine arteries.", "content": "Helically cut strips of canine cerebral, coronary, femoral, mesenteric and renal arteries were contracted with prostaglandin F2alpha. In response to 10(-4)M nicotine, cerebral arterial strips showed a transient relaxation, which was abolished by hexamethonium, cocaine and propranolol but was not significantly influenced by sotalol and tetrodotoxin. In coronary arteries, biphasic response, relaxation followed by contraction, to 8 X 10(-4)M nicotine and contractile response to 10(-4)M nicotine were not influenced by hexamethonium, cocaine and propranolol. Initial contraction and relaxation of femoral arteries induced by nicotine were abolished by hexamethonium and cocaine. Phentolamine (2 X 10(-7)M) attenuated the contraction but not the relaxation, while sotalol (10(-5)M) reduced the relaxation without alterations in the contractile response. In mesenteric and renal arteries, the contractile response to nicotine was abolished by hexamethonium, cocaine, bretylium and phentolamine, but was attenuated only partially by tetrodotoxin. It may be concluded that nicotine exerts a relaxation in cerebral arteries by a mechanism different from the adrenergic one, and a non-specific relaxation and contraction in coronary arteries. It appears that initial contractions of femoral, mesenteric and renal arteries and also relaxation of femoral arteries in response to nicotine are associated with the release of noradrenaline; however, the mechanism of the amine release is different from that with transmural stimulation, in which the nerve action potential is involved.", "contents": "Regional differences in the response to nicotine in isolated canine arteries. Helically cut strips of canine cerebral, coronary, femoral, mesenteric and renal arteries were contracted with prostaglandin F2alpha. In response to 10(-4)M nicotine, cerebral arterial strips showed a transient relaxation, which was abolished by hexamethonium, cocaine and propranolol but was not significantly influenced by sotalol and tetrodotoxin. In coronary arteries, biphasic response, relaxation followed by contraction, to 8 X 10(-4)M nicotine and contractile response to 10(-4)M nicotine were not influenced by hexamethonium, cocaine and propranolol. Initial contraction and relaxation of femoral arteries induced by nicotine were abolished by hexamethonium and cocaine. Phentolamine (2 X 10(-7)M) attenuated the contraction but not the relaxation, while sotalol (10(-5)M) reduced the relaxation without alterations in the contractile response. In mesenteric and renal arteries, the contractile response to nicotine was abolished by hexamethonium, cocaine, bretylium and phentolamine, but was attenuated only partially by tetrodotoxin. It may be concluded that nicotine exerts a relaxation in cerebral arteries by a mechanism different from the adrenergic one, and a non-specific relaxation and contraction in coronary arteries. It appears that initial contractions of femoral, mesenteric and renal arteries and also relaxation of femoral arteries in response to nicotine are associated with the release of noradrenaline; however, the mechanism of the amine release is different from that with transmural stimulation, in which the nerve action potential is involved."} {"id": "PMID:1253817", "title": "Antagonism of the hyperactivity induced by dopamine applied intracerebrally to the nucleus accumbens septi by typical neuroleptics and by clozapine, sulpiride and thioridazine.", "content": "Dopamine administered intracerebrally to the nucleus accumbens septi was shown to induce a dose-dependent hyperactivity following pretreatment with nialamide. This effect was optimum following the injection of 50 mug dopamine. The hyperactivity induced by this dose of dopamine was inhibited by the i.p. injection of both the typical neuroleptic agents, haloperidol, fluphenazine, pimozide and clothiapine (0.05--0.5 mg/kg i.p.), and the atypical neuroleptics clozapine, sulpiride and thioridazine (0.5--20 mg/kg i.p.) although, generally, the doses required ot the latter were in the order of 20--100 times those of the typical agents to produce an equivalent effect. In contrast, cataleptic doses of metoclopramide (10--30 mg/kg i.p.) failed to reduce the dopamine-induced hyperactivity: aceperone and propranolol were similarly ineffective. However, inhibition of hyperactivity was recorded following the peripheral administration of the antimanic drug, IB503. It is suggested that the ability of a drug to antagonise the hyperactivity induced by the injection of dopamine into the nucleus accumbens septi may be of value in the detection of antipsychotic activity.", "contents": "Antagonism of the hyperactivity induced by dopamine applied intracerebrally to the nucleus accumbens septi by typical neuroleptics and by clozapine, sulpiride and thioridazine. Dopamine administered intracerebrally to the nucleus accumbens septi was shown to induce a dose-dependent hyperactivity following pretreatment with nialamide. This effect was optimum following the injection of 50 mug dopamine. The hyperactivity induced by this dose of dopamine was inhibited by the i.p. injection of both the typical neuroleptic agents, haloperidol, fluphenazine, pimozide and clothiapine (0.05--0.5 mg/kg i.p.), and the atypical neuroleptics clozapine, sulpiride and thioridazine (0.5--20 mg/kg i.p.) although, generally, the doses required ot the latter were in the order of 20--100 times those of the typical agents to produce an equivalent effect. In contrast, cataleptic doses of metoclopramide (10--30 mg/kg i.p.) failed to reduce the dopamine-induced hyperactivity: aceperone and propranolol were similarly ineffective. However, inhibition of hyperactivity was recorded following the peripheral administration of the antimanic drug, IB503. It is suggested that the ability of a drug to antagonise the hyperactivity induced by the injection of dopamine into the nucleus accumbens septi may be of value in the detection of antipsychotic activity."} {"id": "PMID:1253818", "title": "Pharmacologic analysis of papaverine-induced positive chronotropic and inotropic effects.", "content": "Effects of papaverine on sinus rate and atrial contractility were investigated using the isolated atrium preparation of the dog perfused with heparinized arterial blood led from a support dog. When papaverine was injected into the cannulated sinus node artery, positive chronotropic and inotropic responses were dose-relatedly produced from about 3 mug. At a dose level above 100 mug, papaverine induced initially slightly negative chronotropic and inotropic effects followed by marked positive ones. Papaverine-induced positive chronotropic and inotropic effects (P-PCIE) were not influenced by treatment with tetrodotoxin which blocked the action of nicotine. P-PCIE were slightly suppressed by an adrenergic beta-blocking agent, alprenolol, which blocked the action of norepinephrine. They were however potentiated by treatment with desmethylimipramine which completely blocked the action of tyramine. A large amount of MnCl2 suppressed the actions of both papaverine and norepinephrine. Papaverine-induced negative chronotropic and inotropic effects were not influenced by atropine treatment. In addition, papaverine slightly potentiated the negative chronotropic and inotropic responses to adenosine. From these results, it appears that papaverine has a direct stimulating property on sinus rate and atrial contractility which may be due to inhibition of phosphodiesterase and successive accumulation of cyclic AMP. Moreover, papaverine may partially cause catecholamine release from adrenergic nerve fibers and it may inhibit the adenosine uptake mechanism.", "contents": "Pharmacologic analysis of papaverine-induced positive chronotropic and inotropic effects. Effects of papaverine on sinus rate and atrial contractility were investigated using the isolated atrium preparation of the dog perfused with heparinized arterial blood led from a support dog. When papaverine was injected into the cannulated sinus node artery, positive chronotropic and inotropic responses were dose-relatedly produced from about 3 mug. At a dose level above 100 mug, papaverine induced initially slightly negative chronotropic and inotropic effects followed by marked positive ones. Papaverine-induced positive chronotropic and inotropic effects (P-PCIE) were not influenced by treatment with tetrodotoxin which blocked the action of nicotine. P-PCIE were slightly suppressed by an adrenergic beta-blocking agent, alprenolol, which blocked the action of norepinephrine. They were however potentiated by treatment with desmethylimipramine which completely blocked the action of tyramine. A large amount of MnCl2 suppressed the actions of both papaverine and norepinephrine. Papaverine-induced negative chronotropic and inotropic effects were not influenced by atropine treatment. In addition, papaverine slightly potentiated the negative chronotropic and inotropic responses to adenosine. From these results, it appears that papaverine has a direct stimulating property on sinus rate and atrial contractility which may be due to inhibition of phosphodiesterase and successive accumulation of cyclic AMP. Moreover, papaverine may partially cause catecholamine release from adrenergic nerve fibers and it may inhibit the adenosine uptake mechanism."} {"id": "PMID:1253819", "title": "Studies on drug-induced neuropathies. III. Motor nerve deficit in cats with experimental acrylamide neuropathy.", "content": "To assess motor nerve and motor nerve terminal function in acrylamide neuropathy, cats were given i.m. injections of acrylamide (15 mg/kg) daily for 10 days to induce a peripheral neuropathy. Tests of function were performed on the day of the 10th injection (day 0) and 7, 21 and 35 days thereafter. In untreated animals tetanic conditioning evoked stimulus-bound repetition (SBR) in 85% of soleus alpha-motoneurones. Following administration of acrylamide, the percent of axons elaborating SBR were: day 0 -- 79%, day 7 -- 71%, day 21 -- 31%, day 35 -- 22%. The response of soleus muscle to SBR is normally a post-tetanic potentiation (PTP) of contractile tension which is proportional to the tetanic conditioning frequency; during the development of the neuropathy, PTP in response to all tetanic frequencies progressively declined, concomitant with and as a result of the declining incidence of SBR. These data indicate that initial functional alterations in motor nerves during acrylamide neuropathy occurs at the level of the nerve terminal, preceding alterations in conduction velocities in the axons. However, the motor nerve deficit is not adequate, in either time to onset or severity, to account for the clinical manifestations of the neuropathy. The possible contribution to clinical signs of the neuropathy made by lesions to other peripheral nerves is discussed.", "contents": "Studies on drug-induced neuropathies. III. Motor nerve deficit in cats with experimental acrylamide neuropathy. To assess motor nerve and motor nerve terminal function in acrylamide neuropathy, cats were given i.m. injections of acrylamide (15 mg/kg) daily for 10 days to induce a peripheral neuropathy. Tests of function were performed on the day of the 10th injection (day 0) and 7, 21 and 35 days thereafter. In untreated animals tetanic conditioning evoked stimulus-bound repetition (SBR) in 85% of soleus alpha-motoneurones. Following administration of acrylamide, the percent of axons elaborating SBR were: day 0 -- 79%, day 7 -- 71%, day 21 -- 31%, day 35 -- 22%. The response of soleus muscle to SBR is normally a post-tetanic potentiation (PTP) of contractile tension which is proportional to the tetanic conditioning frequency; during the development of the neuropathy, PTP in response to all tetanic frequencies progressively declined, concomitant with and as a result of the declining incidence of SBR. These data indicate that initial functional alterations in motor nerves during acrylamide neuropathy occurs at the level of the nerve terminal, preceding alterations in conduction velocities in the axons. However, the motor nerve deficit is not adequate, in either time to onset or severity, to account for the clinical manifestations of the neuropathy. The possible contribution to clinical signs of the neuropathy made by lesions to other peripheral nerves is discussed."} {"id": "PMID:1253820", "title": "Effect of nomifensine on acetylcholine and choline in the rat striatum and brainstem.", "content": "Nomifensine, at a dose of 40 mg/kg, slightly but significantly increased rat striatal acetylcholine 60 min after i.p. administration without affecting choline levels or choline O-acetyltransferase and cholinesterase activities. This drug had no effect on brainstem acetylcholine. In contrast, d-amphetamine and desipramine both produced a small but significant increase in brainstem acetylcholine. It is suggested that nomifensine increased striatal acetylcholine indirectly through blockade of dopamine uptake.", "contents": "Effect of nomifensine on acetylcholine and choline in the rat striatum and brainstem. Nomifensine, at a dose of 40 mg/kg, slightly but significantly increased rat striatal acetylcholine 60 min after i.p. administration without affecting choline levels or choline O-acetyltransferase and cholinesterase activities. This drug had no effect on brainstem acetylcholine. In contrast, d-amphetamine and desipramine both produced a small but significant increase in brainstem acetylcholine. It is suggested that nomifensine increased striatal acetylcholine indirectly through blockade of dopamine uptake."} {"id": "PMID:1253821", "title": "Central hyperglycemic effect of carbachol in rats.", "content": "Intraventricular injection of carbachol produces hyperglycemia in rats at doses which are ineffective when given subcutaneously. This effect is suppressed by intraventricular administration of small amounts of atropine, further supporting the suggestion that the effect of carbachol is due to its action on central cholinergic receptors. Carbachol-induced hyperglycemia is not abolished by adrenalectomy and hypophysectomy, or pretreatment with reserpine.", "contents": "Central hyperglycemic effect of carbachol in rats. Intraventricular injection of carbachol produces hyperglycemia in rats at doses which are ineffective when given subcutaneously. This effect is suppressed by intraventricular administration of small amounts of atropine, further supporting the suggestion that the effect of carbachol is due to its action on central cholinergic receptors. Carbachol-induced hyperglycemia is not abolished by adrenalectomy and hypophysectomy, or pretreatment with reserpine."} {"id": "PMID:1253822", "title": "Fenfluramine: long-term reduction in brain serotonin (5-hydroxytryptamine).", "content": "A single oral dose of 15 mg/kg of fenfluramine reduced the level of serotonin in rat brain to 48, 51 and 63% of control at 1, 15 and 30 days, respectively, after administration. 3 mg/kg p.o. of the drug caused a smaller but significant diminution in brain serotonin. At the 3 mg/kg dose level, the decreases in serotonin were, at least partially, cumulative following multiple injections spaced 24 hr apart. Brains removed 14 days after the 5th daily injection of 5 mg/kg p.o. of fenfluramine had only 60% of the concentration of serotonin found in brains from control animals. These findings demonstrate that fenfluramine has a long-lasting action on serotonin-containing neurons in brain.", "contents": "Fenfluramine: long-term reduction in brain serotonin (5-hydroxytryptamine). A single oral dose of 15 mg/kg of fenfluramine reduced the level of serotonin in rat brain to 48, 51 and 63% of control at 1, 15 and 30 days, respectively, after administration. 3 mg/kg p.o. of the drug caused a smaller but significant diminution in brain serotonin. At the 3 mg/kg dose level, the decreases in serotonin were, at least partially, cumulative following multiple injections spaced 24 hr apart. Brains removed 14 days after the 5th daily injection of 5 mg/kg p.o. of fenfluramine had only 60% of the concentration of serotonin found in brains from control animals. These findings demonstrate that fenfluramine has a long-lasting action on serotonin-containing neurons in brain."} {"id": "PMID:1253823", "title": "Acute gastric ulcer formation in response to electrical vagal stimulation in rats.", "content": "Intermittent electrical stimulation of the left cervical vagus increased intragastric pressure and induced a 100% incidence of haemorrhagic ulcers in the glandular mucosa of rat stomachs. Atropine pretreatment of sub-diaphragmatic vagotomy prevented these effects. The findings substantiate the idea that stress-induced glandular ulcers result from vagal-mediated increased gastric contractions.", "contents": "Acute gastric ulcer formation in response to electrical vagal stimulation in rats. Intermittent electrical stimulation of the left cervical vagus increased intragastric pressure and induced a 100% incidence of haemorrhagic ulcers in the glandular mucosa of rat stomachs. Atropine pretreatment of sub-diaphragmatic vagotomy prevented these effects. The findings substantiate the idea that stress-induced glandular ulcers result from vagal-mediated increased gastric contractions."} {"id": "PMID:1253824", "title": "Ethanol, indomethacin and gastric acid secretion in the rat.", "content": "In the anesthetized rat, 10% ethanol in the gastric lumen causes a total cessation of the secretion of gastric acid within 30--60 min. This effect is inhibited by pretreatment with indomethacin, which is a potent inhibitor of prostaglandin synthesis. Therefore, the inhibitory effect of local ethanol on gastric acid secretion in the rat may be mediated, at least partly, by increased synthesis of prostaglandins.", "contents": "Ethanol, indomethacin and gastric acid secretion in the rat. In the anesthetized rat, 10% ethanol in the gastric lumen causes a total cessation of the secretion of gastric acid within 30--60 min. This effect is inhibited by pretreatment with indomethacin, which is a potent inhibitor of prostaglandin synthesis. Therefore, the inhibitory effect of local ethanol on gastric acid secretion in the rat may be mediated, at least partly, by increased synthesis of prostaglandins."} {"id": "PMID:1253825", "title": "Release of 3H-alpha-methyl-m-tyramine from rat striatum in vitro.", "content": "Release of 3H-d-alpha-methyl-m-tyramine (3H-MMTA), a false dopaminergic transmitter, from rat striatum was studied in vitro. After its initial uptake, 3H-MMTA was released by high K+ and by amphetamine. The release requirements were essentially the same as those known to exist for release of dopamine in vitro. These studies indicate that 3H-MMTA might serve as a useful tool with which to study dopamine release mechanisms in vitro.", "contents": "Release of 3H-alpha-methyl-m-tyramine from rat striatum in vitro. Release of 3H-d-alpha-methyl-m-tyramine (3H-MMTA), a false dopaminergic transmitter, from rat striatum was studied in vitro. After its initial uptake, 3H-MMTA was released by high K+ and by amphetamine. The release requirements were essentially the same as those known to exist for release of dopamine in vitro. These studies indicate that 3H-MMTA might serve as a useful tool with which to study dopamine release mechanisms in vitro."} {"id": "PMID:1253826", "title": "Role of DA in the stimulant effect of DITA in mice; comparison with d-amphetamine.", "content": "The effect of DL-alpha methyltyrosine (alpha-MT), 6-hydroxydopa (6-OH DOPA), haloperidol, phenoxybenzamine and propranolol on the stimulant activity of the anorexigenic agents (3',4'-dichloro-2-(2-imidazolin-2-yl-thio)-acetophenone HBr) (DITA) and d-amphetamine was studied in male mice. The pretreatment of mice with alpha-MT, (32, 64 mg/kg i.p.), significantly reduced the increase in motor activity induced by DITA or d-amphetamine. On the other hand, pretreatment of mice with 6-OH DOPA, (100, 150 mg/kg, i.v.), did not significantly after the stimulant effect of either DITA or d-amphetamine. In the case of haloperidol, it significantly reduced the increase of motor activity induced by DITA or d-amphetamine; propranolol and phenoxybenzamine were ineffective. Our results support the hypothesis that the stimulant effect of DITA and d-amphetamine depends mainly on the integrity of the central dopaminergic rather than the noradrenergic system.", "contents": "Role of DA in the stimulant effect of DITA in mice; comparison with d-amphetamine. The effect of DL-alpha methyltyrosine (alpha-MT), 6-hydroxydopa (6-OH DOPA), haloperidol, phenoxybenzamine and propranolol on the stimulant activity of the anorexigenic agents (3',4'-dichloro-2-(2-imidazolin-2-yl-thio)-acetophenone HBr) (DITA) and d-amphetamine was studied in male mice. The pretreatment of mice with alpha-MT, (32, 64 mg/kg i.p.), significantly reduced the increase in motor activity induced by DITA or d-amphetamine. On the other hand, pretreatment of mice with 6-OH DOPA, (100, 150 mg/kg, i.v.), did not significantly after the stimulant effect of either DITA or d-amphetamine. In the case of haloperidol, it significantly reduced the increase of motor activity induced by DITA or d-amphetamine; propranolol and phenoxybenzamine were ineffective. Our results support the hypothesis that the stimulant effect of DITA and d-amphetamine depends mainly on the integrity of the central dopaminergic rather than the noradrenergic system."} {"id": "PMID:1253827", "title": "Comparative action of fenfluramine on the uptake and release of serotonin and dopamine.", "content": "The anorectic agent, fenfluramine, proves to be a good inhibitor of serotonin uptake in vitro, in synaptosomes from rat whole brain (IC50 = 8.5 +/- 0.6 X 10(-7) M). After administration in vivo, its inhibitory activity in vitro equals that of chlorimipramine and in contrast to the latter, its effect is of long duration. Fenfluramine is also effective in promoting the release of serotonin from pre-loaded synaptosomes. In comparison, the structurally related compound, amphetamine, has little activity with respect to these serotonin mechanisms. It is, however, active both in inhibiting the uptake of dopamine and in promoting its release, whereas fenfluramine is inactive. The implication of these mechanisms in the serotonin-depleting capacity as well as in the anorectic activity of fenfluramine is discussed.", "contents": "Comparative action of fenfluramine on the uptake and release of serotonin and dopamine. The anorectic agent, fenfluramine, proves to be a good inhibitor of serotonin uptake in vitro, in synaptosomes from rat whole brain (IC50 = 8.5 +/- 0.6 X 10(-7) M). After administration in vivo, its inhibitory activity in vitro equals that of chlorimipramine and in contrast to the latter, its effect is of long duration. Fenfluramine is also effective in promoting the release of serotonin from pre-loaded synaptosomes. In comparison, the structurally related compound, amphetamine, has little activity with respect to these serotonin mechanisms. It is, however, active both in inhibiting the uptake of dopamine and in promoting its release, whereas fenfluramine is inactive. The implication of these mechanisms in the serotonin-depleting capacity as well as in the anorectic activity of fenfluramine is discussed."} {"id": "PMID:1253828", "title": "Anticonvulsant activity of delta9-tetrahydrocannabinol compared with three other drugs.", "content": "Delta9-tetrahydrocannabinol (THC) was compared with diphenylhydantoin (DPH), phenobarbital (PB) and chlordiazepoxide (CDP) using several standard laboratory procedures to determine anticonvulsant activity in mice, i.e., the maximal electroshock test (MES), and seizures induced by pentylenetetrazol, strychnine and nicotine. In the MES test, THC was the least potent and DPH the most potent blocker of hind limb tonic extensor convulsions whereas THC was the most potent and DPH the least potent in increasing the latency to this response and in preventing mortality. Seizures and mortality induced by pentylenetetrazol or by strychnine were enhanced by THC and DPH and were blocked by PB and CDP. In the test with nicotine, none of the four anticonvulsant agents prevented seizures; DPH was the only one which failed to increase latency; THC and DPH were less potent than PB and CDP in preventing mortality. THC most closely resembled DPH in the tests with chemical convulsant agents, but a sedative action of THC, resembling that of PB and CDP, was indicated by low ED5 0 for increased latency and for prevention of mortality in the MES test.", "contents": "Anticonvulsant activity of delta9-tetrahydrocannabinol compared with three other drugs. Delta9-tetrahydrocannabinol (THC) was compared with diphenylhydantoin (DPH), phenobarbital (PB) and chlordiazepoxide (CDP) using several standard laboratory procedures to determine anticonvulsant activity in mice, i.e., the maximal electroshock test (MES), and seizures induced by pentylenetetrazol, strychnine and nicotine. In the MES test, THC was the least potent and DPH the most potent blocker of hind limb tonic extensor convulsions whereas THC was the most potent and DPH the least potent in increasing the latency to this response and in preventing mortality. Seizures and mortality induced by pentylenetetrazol or by strychnine were enhanced by THC and DPH and were blocked by PB and CDP. In the test with nicotine, none of the four anticonvulsant agents prevented seizures; DPH was the only one which failed to increase latency; THC and DPH were less potent than PB and CDP in preventing mortality. THC most closely resembled DPH in the tests with chemical convulsant agents, but a sedative action of THC, resembling that of PB and CDP, was indicated by low ED5 0 for increased latency and for prevention of mortality in the MES test."} {"id": "PMID:1253829", "title": "Aporphines. 16. Action of aporphine alkaloids on locomotor activity in rats with 6-hydroxydopamine lesions of the nucleus accumbens.", "content": "(-)-Apomorphine and (+/-)-N-n-propylnorapomorphine (+/-)-NPA) produce stereotypy but not locomotor activity in normal rats. In rats with selective bilateral lesions of dopamine terminals in the nucleus accumbens induced by microinjection of 6-hydroxydopamine both compounds produced a marked stimulation of locomotor activity. (+/-)-NPA was considerably more potent than (-) -apomorphine. The maximal intensity of stimulation produced by the two drugs was, however, similar. The locomotor stimulant effects of (-)-apomorphine were inhibited by (+)-bulbocapnine (20 mg/kg) or pimozide (0.5 mg/kg). (+/-)-N-n-Propylnorapocodeine also produced a long-lasting stimulation of locomotor activity. (+/-)-Aporphine, (+/-)-isopomorphine, (-)-1,2-dihydroxyaporphine, and (-)-nuciferine were all inactive in stimulating locomotor activity.", "contents": "Aporphines. 16. Action of aporphine alkaloids on locomotor activity in rats with 6-hydroxydopamine lesions of the nucleus accumbens. (-)-Apomorphine and (+/-)-N-n-propylnorapomorphine (+/-)-NPA) produce stereotypy but not locomotor activity in normal rats. In rats with selective bilateral lesions of dopamine terminals in the nucleus accumbens induced by microinjection of 6-hydroxydopamine both compounds produced a marked stimulation of locomotor activity. (+/-)-NPA was considerably more potent than (-) -apomorphine. The maximal intensity of stimulation produced by the two drugs was, however, similar. The locomotor stimulant effects of (-)-apomorphine were inhibited by (+)-bulbocapnine (20 mg/kg) or pimozide (0.5 mg/kg). (+/-)-N-n-Propylnorapocodeine also produced a long-lasting stimulation of locomotor activity. (+/-)-Aporphine, (+/-)-isopomorphine, (-)-1,2-dihydroxyaporphine, and (-)-nuciferine were all inactive in stimulating locomotor activity."} {"id": "PMID:1253830", "title": "[Fuorometric analysis of delta-9-tetrahydrocannabinol and its metabolites in urine].", "content": "The high number of drug addicts using marijuana (Cannabis sativa var. indica) under various forms has lead research workers to propound many a method for the characterization and assaying of delta9-tetrahydrocannabinol (delta9-THC) and its metabolites in biological fluids. Some of them are based on labelled materials, radioimmuno-chemistry, gas chromatography alone or combined with mass spectrometry. No mention of a purely chemical method has been found in the literature, with the exception of characterizations using thin-layer chromatography and formation of dansylated derivatives (5 to 9, 11 to 14, 16, 17, 18, 22, 23, 26, 31, 32, 34, to 38, 43 to 48, 59).", "contents": "[Fuorometric analysis of delta-9-tetrahydrocannabinol and its metabolites in urine]. The high number of drug addicts using marijuana (Cannabis sativa var. indica) under various forms has lead research workers to propound many a method for the characterization and assaying of delta9-tetrahydrocannabinol (delta9-THC) and its metabolites in biological fluids. Some of them are based on labelled materials, radioimmuno-chemistry, gas chromatography alone or combined with mass spectrometry. No mention of a purely chemical method has been found in the literature, with the exception of characterizations using thin-layer chromatography and formation of dansylated derivatives (5 to 9, 11 to 14, 16, 17, 18, 22, 23, 26, 31, 32, 34, to 38, 43 to 48, 59)."} {"id": "PMID:1253832", "title": "[Bromide vegetating skin diseases after treatment by a bromocalcic specialty].", "content": "The authors report on a case of vegetating bromoderma observed after therapy with bromocalcic speciality (Calcibronat). Repeated bromine determinations in body fluids enabled, while reconsidering the metabolism of this halogen, to monitor its elimination.", "contents": "[Bromide vegetating skin diseases after treatment by a bromocalcic specialty]. The authors report on a case of vegetating bromoderma observed after therapy with bromocalcic speciality (Calcibronat). Repeated bromine determinations in body fluids enabled, while reconsidering the metabolism of this halogen, to monitor its elimination."} {"id": "PMID:1253831", "title": "[Lactic acidosis induced by excessive ingestion of metformin].", "content": "The authors report on a case of lethal lactate acidosis during acute metformine and barbiturate poisoning. The study of energetic substrates and glucoregulation hormones demonstrated a blockade of hepatic gluconeogenesis.", "contents": "[Lactic acidosis induced by excessive ingestion of metformin]. The authors report on a case of lethal lactate acidosis during acute metformine and barbiturate poisoning. The study of energetic substrates and glucoregulation hormones demonstrated a blockade of hepatic gluconeogenesis."} {"id": "PMID:1253855", "title": "Role of the kidneys in thrombopoietin production.", "content": "Extracts of plasma from normal rats, rats injected with rabbit anti-rat platelet serum (RARPS), nephrectomized rats and nephrectomized rats injected with RARPS were tested in thrombocytotic mice for the presence of thrombopoietin. Only fractions of plasma from unoperated rats that had been made thrombocytopenic by injection of RARPS gave positive results for thrombopoietin. The results suggest that the kidneys play a role in thrombopoietin production.", "contents": "Role of the kidneys in thrombopoietin production. Extracts of plasma from normal rats, rats injected with rabbit anti-rat platelet serum (RARPS), nephrectomized rats and nephrectomized rats injected with RARPS were tested in thrombocytotic mice for the presence of thrombopoietin. Only fractions of plasma from unoperated rats that had been made thrombocytopenic by injection of RARPS gave positive results for thrombopoietin. The results suggest that the kidneys play a role in thrombopoietin production."} {"id": "PMID:1253856", "title": "Cerebello-olivary fibers: their origin, course and distribution in the North American opossum.", "content": "Although degeneration techniques suggest that cerebello-olivary fibers are limited in their origin and distribution, horseradish peroxidase and autoradiographic experiments make it clear that they arise within all cerebellar nuclei and project to most, if not all, areas of the contralateral inferior olive. Autoradiographic preparations show that cerebello-olivary fibers are highly ordered and suggest that the dentate nucleus projects primarily to the principal olive, the interpositus anterior relays particularly heavy to the dorsal accessory nucleus and the interpositus posterior distributes extensively to the medial accessory complex. Evidence for a small projection from the fastigial nucleus to the caudal medial accessory nucleus is also available. However, it appears clear that neither the dentate nor the interpositus nuclei project to just one subdivision of the olive. For example, although dentate fibers end extensively within the principal nucleus some of them also distribute to portions of the medial accessory nucleus and perhaps the dorsal accessory nucleus as well. The medial accessory olive is particularly complex and at rostral levels receives input from both interposed and dentate nuclei, whereas more caudally it receives a projection from the fastigial nucleus. Olivary fibers from both the interposed and dentate nuclei traverse the brachium conjunctivum descendens and distribute primarily to the rostral 2/3 to 3/4 of the olive, whereas those from fastigial neurons take a different route and end more caudally. Experiments utilizing horseradish peroxidase as a retrograde tracer suggest that cerebello-olivary fibers from both the interpositus anterior and dentate nuclei take origin from a population of generally small neurons.", "contents": "Cerebello-olivary fibers: their origin, course and distribution in the North American opossum. Although degeneration techniques suggest that cerebello-olivary fibers are limited in their origin and distribution, horseradish peroxidase and autoradiographic experiments make it clear that they arise within all cerebellar nuclei and project to most, if not all, areas of the contralateral inferior olive. Autoradiographic preparations show that cerebello-olivary fibers are highly ordered and suggest that the dentate nucleus projects primarily to the principal olive, the interpositus anterior relays particularly heavy to the dorsal accessory nucleus and the interpositus posterior distributes extensively to the medial accessory complex. Evidence for a small projection from the fastigial nucleus to the caudal medial accessory nucleus is also available. However, it appears clear that neither the dentate nor the interpositus nuclei project to just one subdivision of the olive. For example, although dentate fibers end extensively within the principal nucleus some of them also distribute to portions of the medial accessory nucleus and perhaps the dorsal accessory nucleus as well. The medial accessory olive is particularly complex and at rostral levels receives input from both interposed and dentate nuclei, whereas more caudally it receives a projection from the fastigial nucleus. Olivary fibers from both the interposed and dentate nuclei traverse the brachium conjunctivum descendens and distribute primarily to the rostral 2/3 to 3/4 of the olive, whereas those from fastigial neurons take a different route and end more caudally. Experiments utilizing horseradish peroxidase as a retrograde tracer suggest that cerebello-olivary fibers from both the interpositus anterior and dentate nuclei take origin from a population of generally small neurons."} {"id": "PMID:1253857", "title": "The role of cutaneous afferents from the distal hindlimb in the regulation of the step cycle of thalamic cats.", "content": "The pad and the plantar surface of the foot were stimulated electrically in thalamic cats. Weak stimulation evoked an extensor reflex in the animal at rest. The same stimuli in a spontaneously walking animal applied during the stance phase produced an increase both in amplitude and duration of the ongoing extensor activity. When given during the swing phase, the stimuli either prolonged the ongoing flexor activity and/or shortened the following extensor burst. These changes in flexor and extensor burst duration were reflected in changes in the step cycle duration. Similar results were seen with direct stimulation of the sural nerve. For the latter experiments the ipsilateral hindlimb was fixed and denervated except for the ankle extensors and flexors, which showed rhythmic contractions correlated normally with the walking movements of the three remaining limbs. At rest, threshold stimulation of the sural nerve evoked a reflex contraction in the triceps surae of the fixed leg. The same stimuli applied during the contraction phase of the fixed triceps surae during walking resulted in a larger and longer extensor contraction and a delay of the following flexion. Stimulation during the relaxation phase of the fixed triceps surae reduced the duration of the following contraction phase. The findings are discussed in relation to the possible role of cutaneous input during locomotion.", "contents": "The role of cutaneous afferents from the distal hindlimb in the regulation of the step cycle of thalamic cats. The pad and the plantar surface of the foot were stimulated electrically in thalamic cats. Weak stimulation evoked an extensor reflex in the animal at rest. The same stimuli in a spontaneously walking animal applied during the stance phase produced an increase both in amplitude and duration of the ongoing extensor activity. When given during the swing phase, the stimuli either prolonged the ongoing flexor activity and/or shortened the following extensor burst. These changes in flexor and extensor burst duration were reflected in changes in the step cycle duration. Similar results were seen with direct stimulation of the sural nerve. For the latter experiments the ipsilateral hindlimb was fixed and denervated except for the ankle extensors and flexors, which showed rhythmic contractions correlated normally with the walking movements of the three remaining limbs. At rest, threshold stimulation of the sural nerve evoked a reflex contraction in the triceps surae of the fixed leg. The same stimuli applied during the contraction phase of the fixed triceps surae during walking resulted in a larger and longer extensor contraction and a delay of the following flexion. Stimulation during the relaxation phase of the fixed triceps surae reduced the duration of the following contraction phase. The findings are discussed in relation to the possible role of cutaneous input during locomotion."} {"id": "PMID:1253858", "title": "Pathways for the vestibulo-ocular reflex excitation arising from semicircular canals of rabbits.", "content": "In anesthetized albino rabbits, ampullary branches of the vestibular nerve were stimulated electrically. Prominent and stable reflex contraction was induced in extra-ocular muscles by applying single current pulses of relatively long duration, 3-5 msec. Survey with a glass microelectrode revealed that, during application of relatively wide pulses to a canal, primary vestibular fibers discharged impulses repetitively at a rate as high as 300-1400/sec and that after being transmitted across second-order vestibular neurons these impulses built up summated EPSPs in oculomotor neurons, large enough to trigger off motoneuronal discharges. From each semicircular canal, prominent reflex contraction was evoked selectively in two muslces; from the anterior canal in the ipsilateral superior rectus and contralateral inferior oblique; from the horizontal canal in the ipsilateral medial rectus and contralateral lateral rectus; and from the posterior rectus. Acute lesion experiments indicated that signals for this excitation reached IIIrd and IVth nuclei via three different pathways; from the anterior canal through the ipsilateral brachium conjunctivum, from the horizontal canal through the ipsilateral fasciculus longitudinalis medialis and from the posterior canal through the contralateral fasciculus longitudinalis medialis.", "contents": "Pathways for the vestibulo-ocular reflex excitation arising from semicircular canals of rabbits. In anesthetized albino rabbits, ampullary branches of the vestibular nerve were stimulated electrically. Prominent and stable reflex contraction was induced in extra-ocular muscles by applying single current pulses of relatively long duration, 3-5 msec. Survey with a glass microelectrode revealed that, during application of relatively wide pulses to a canal, primary vestibular fibers discharged impulses repetitively at a rate as high as 300-1400/sec and that after being transmitted across second-order vestibular neurons these impulses built up summated EPSPs in oculomotor neurons, large enough to trigger off motoneuronal discharges. From each semicircular canal, prominent reflex contraction was evoked selectively in two muslces; from the anterior canal in the ipsilateral superior rectus and contralateral inferior oblique; from the horizontal canal in the ipsilateral medial rectus and contralateral lateral rectus; and from the posterior rectus. Acute lesion experiments indicated that signals for this excitation reached IIIrd and IVth nuclei via three different pathways; from the anterior canal through the ipsilateral brachium conjunctivum, from the horizontal canal through the ipsilateral fasciculus longitudinalis medialis and from the posterior canal through the contralateral fasciculus longitudinalis medialis."} {"id": "PMID:1253859", "title": "Postsynaptic inhibition of oculomotor neurons involved in vestibulo-ocular reflexes arising from semicircular canals of rabbits.", "content": "In anesthetized albino rabbits, electric stimulation of vestibular nerve branches innervating semicircular canals produced not only reflex contraction in certain extraocular muscles, but also a transient relaxation in others. From relaxing muscles was recorded a slow muscle potential that reflected depression of spontaneous spike discharges in muscle fibers. When recorded monophasically, spontaneous spikes of muscle fibers were superposed to form a direct current potential, and depression of the spikes resulted in a transient reduction of this direct current potential, i.e., the slow muscle potential. The slow muscle potential was correlated to the postsynaptic inhibition induced in oculomotor neurons through the vestibulo-ocular reflex are for the following reasons; its latency was compatible with that of the IPSP's recorded from oculomotor neurons; it was removed by severing axons of the inhibitory second-order vestibular neurons; it was blocked by intravenous injection of picrotoxin as were the IPSP's in oculomotor neurons. By recording slow muscle potentials, a specific canal-muscle relationship for the vestibulo-ocular reflex inhibition of oculomotor neurons was shown to be complementary to that obtained for the vestibulo-ocular reflex excitation.", "contents": "Postsynaptic inhibition of oculomotor neurons involved in vestibulo-ocular reflexes arising from semicircular canals of rabbits. In anesthetized albino rabbits, electric stimulation of vestibular nerve branches innervating semicircular canals produced not only reflex contraction in certain extraocular muscles, but also a transient relaxation in others. From relaxing muscles was recorded a slow muscle potential that reflected depression of spontaneous spike discharges in muscle fibers. When recorded monophasically, spontaneous spikes of muscle fibers were superposed to form a direct current potential, and depression of the spikes resulted in a transient reduction of this direct current potential, i.e., the slow muscle potential. The slow muscle potential was correlated to the postsynaptic inhibition induced in oculomotor neurons through the vestibulo-ocular reflex are for the following reasons; its latency was compatible with that of the IPSP's recorded from oculomotor neurons; it was removed by severing axons of the inhibitory second-order vestibular neurons; it was blocked by intravenous injection of picrotoxin as were the IPSP's in oculomotor neurons. By recording slow muscle potentials, a specific canal-muscle relationship for the vestibulo-ocular reflex inhibition of oculomotor neurons was shown to be complementary to that obtained for the vestibulo-ocular reflex excitation."} {"id": "PMID:1253860", "title": "Variability of inter-spike intervals of cat's on-center optic tract fibres activated by steady light spot: a comparative study on X- and Y-fibres.", "content": "Extracellular recordings were made from single on-center optic tract fibres in cats. Light spots of 10sec duration were focussed on the center of the receptive field under 1cd/m2 adaptation luminance by diffuse light. In the maintained discharges at 1 cd/m2, the shape of inter-spike interval histograms (IH) tended to be more skewed in X-fibres than in Y-fibres. As the luminance of the light spot increased, corresponding with the decrease in irregularity of length of inter-spike intervals, the shape of the IHs from X-fibres became symmetrical without noticeable shift of the modal interval peaks. This change was not clear in Y-fibres. The first order serial correlation coefficients showed small negative values in the case of the maintained discharges. These negative values increased with the decrease of the mean intervals of the discharges induced by the light spots, commonly in X- and Y-fibres. The negative correlation of adjacent inter-spike intervals was associated with a change of the shape of some IHs at lower luminances.", "contents": "Variability of inter-spike intervals of cat's on-center optic tract fibres activated by steady light spot: a comparative study on X- and Y-fibres. Extracellular recordings were made from single on-center optic tract fibres in cats. Light spots of 10sec duration were focussed on the center of the receptive field under 1cd/m2 adaptation luminance by diffuse light. In the maintained discharges at 1 cd/m2, the shape of inter-spike interval histograms (IH) tended to be more skewed in X-fibres than in Y-fibres. As the luminance of the light spot increased, corresponding with the decrease in irregularity of length of inter-spike intervals, the shape of the IHs from X-fibres became symmetrical without noticeable shift of the modal interval peaks. This change was not clear in Y-fibres. The first order serial correlation coefficients showed small negative values in the case of the maintained discharges. These negative values increased with the decrease of the mean intervals of the discharges induced by the light spots, commonly in X- and Y-fibres. The negative correlation of adjacent inter-spike intervals was associated with a change of the shape of some IHs at lower luminances."} {"id": "PMID:1253861", "title": "Gravity responses of Purkinje cells in the nodulus.", "content": "In cats, either decerebrated or under chloralose anaesthesia, Purkinje cells (P-cells) of the cerebellar nodulus have been examined with the animal under static lateral tilt (roll +/- 20 degrees). The cell activity was extracellularly recorded and both \"simple\" and \"complex\" spike discharge patterns were studied. In 20 cells out of a population of 198, \"simple\" spike firing was found to be affected by static roll. Ten cells had an alpha-type response, 8 a beta-type, while only single examples of gamma and delta activations were found. Out of 67 Purkinje cells tested for \"complex\" spike activation, 5 were found to be sensitive to static roll, 4 with an alpha or beta response and one with a gamma response. The results are to be attributed to pure otolith activation and show that this input is able to modulate P-cell activity in the nodulus through both the mossy fibre and the climbing fibre systems.", "contents": "Gravity responses of Purkinje cells in the nodulus. In cats, either decerebrated or under chloralose anaesthesia, Purkinje cells (P-cells) of the cerebellar nodulus have been examined with the animal under static lateral tilt (roll +/- 20 degrees). The cell activity was extracellularly recorded and both \"simple\" and \"complex\" spike discharge patterns were studied. In 20 cells out of a population of 198, \"simple\" spike firing was found to be affected by static roll. Ten cells had an alpha-type response, 8 a beta-type, while only single examples of gamma and delta activations were found. Out of 67 Purkinje cells tested for \"complex\" spike activation, 5 were found to be sensitive to static roll, 4 with an alpha or beta response and one with a gamma response. The results are to be attributed to pure otolith activation and show that this input is able to modulate P-cell activity in the nodulus through both the mossy fibre and the climbing fibre systems."} {"id": "PMID:1253862", "title": "Heterogeneity of motor units activating single Golgi tendon organs in cat leg muscles.", "content": "The aim of this study was to investigate whether an individual Golgi tendon organ can signal the contraction of motor units with different physiological properties. The axonal conduction velocity and tetanic tension of motor units were examined in four muscles of the cat leg (peroneus brevis, peroneus longus, tibialis anterior and soleus). The motor units which were found to activate a given tendon organ had contractile properties dispersed over the same range as those of the whole muscle population. The proportion of tendon organ-activating motor units found in the studied samples suggests that altogether, the Golgi tendon organs of a muscle monitor the contraction of every motor unit in this muscle.", "contents": "Heterogeneity of motor units activating single Golgi tendon organs in cat leg muscles. The aim of this study was to investigate whether an individual Golgi tendon organ can signal the contraction of motor units with different physiological properties. The axonal conduction velocity and tetanic tension of motor units were examined in four muscles of the cat leg (peroneus brevis, peroneus longus, tibialis anterior and soleus). The motor units which were found to activate a given tendon organ had contractile properties dispersed over the same range as those of the whole muscle population. The proportion of tendon organ-activating motor units found in the studied samples suggests that altogether, the Golgi tendon organs of a muscle monitor the contraction of every motor unit in this muscle."} {"id": "PMID:1253863", "title": "Electrophysiological studies on the cerebellocerebral projections in monkeys.", "content": "1. Responses evoked by stimulation of the cerebellar and thalamic nuclei were recorded by microelectrodes introduced at various depths in the cerebral cortex of monkeys (Macaca mulatta) under light Nembutal anaesthesia. 2. Stimulation of the medial (fastigial) cerebellar nucleus produced, at a latency of 4-5 msec, deep thalamo-cortical (T-C) responses (surface positive-deep negative potentials) mainly in the medial part of the precentral gyrus (area 4, \"motor area for hindlimb\") and in the superior parietal gyrus (area 5) on both contralateral and ipsilateral sides to the nucleus stimulated. 3. Stimulation of the lateral (dentate) cerebellar nucleus elicited, at a latency of about 3 msec, superficial T-C responses (surface negative-deep positive potentials) predominately in the lateral part of the precentral gyrus (area 4, \"motor area for forelimb and face\") and in the rostromedial part of the gyrus (area 6, premotor area) on the contralateral side. 4. Stimulation of the interpositus cerebellar nucleus set up superficial T-C responses chiefly in the motor area between those influenced by the medial and the lateral cerebellar nucleus stimulation and also in the premotor area on the contralateral side. 5. The respective areas responsive to the medial, interpositus and lateral nucleus stimulation overlapped considerably each other in the motor cortex. 6. Comparison of the responses in the cortex induced by stimulation of the cerebellar and thalamic nuclei indicated different relay portions in and around the VA-VL region of the thalamus for the superficial and the deep T-C responses respectively. 7. Functional implications of the results were discussed in referring to the cerebellocerebral projections in cats.", "contents": "Electrophysiological studies on the cerebellocerebral projections in monkeys. 1. Responses evoked by stimulation of the cerebellar and thalamic nuclei were recorded by microelectrodes introduced at various depths in the cerebral cortex of monkeys (Macaca mulatta) under light Nembutal anaesthesia. 2. Stimulation of the medial (fastigial) cerebellar nucleus produced, at a latency of 4-5 msec, deep thalamo-cortical (T-C) responses (surface positive-deep negative potentials) mainly in the medial part of the precentral gyrus (area 4, \"motor area for hindlimb\") and in the superior parietal gyrus (area 5) on both contralateral and ipsilateral sides to the nucleus stimulated. 3. Stimulation of the lateral (dentate) cerebellar nucleus elicited, at a latency of about 3 msec, superficial T-C responses (surface negative-deep positive potentials) predominately in the lateral part of the precentral gyrus (area 4, \"motor area for forelimb and face\") and in the rostromedial part of the gyrus (area 6, premotor area) on the contralateral side. 4. Stimulation of the interpositus cerebellar nucleus set up superficial T-C responses chiefly in the motor area between those influenced by the medial and the lateral cerebellar nucleus stimulation and also in the premotor area on the contralateral side. 5. The respective areas responsive to the medial, interpositus and lateral nucleus stimulation overlapped considerably each other in the motor cortex. 6. Comparison of the responses in the cortex induced by stimulation of the cerebellar and thalamic nuclei indicated different relay portions in and around the VA-VL region of the thalamus for the superficial and the deep T-C responses respectively. 7. Functional implications of the results were discussed in referring to the cerebellocerebral projections in cats."} {"id": "PMID:1253864", "title": "Ascending long spinal actions on forelimb motoneurons in the acute spinal cat.", "content": "Ascending long spinal reflex system were investigated by means of monosynaptic reflex testing in the acutely spinalized unanesthetized cat. 1. Hindlimb nerve stimulation gave bilateral facilitatory effects on the motoneuron pools of pectoralis major and physiological flexors of the forelimb such as biceps brachii, extensor carpi radialis, extensor digitorum communis, but elicited depressive effects on the physiological extensors such as triceps brachii, flexor carpi radialis, flexor digitorum profundus. 2. In the latissimus dorsi, which is the antagonist of pectoralis major, a depressive effect was elicited by the stimulation of ipsilateral hindlimb nerves, and a facilitatory effect by contralateral stimulation. 3. These effects were evoked mainly from group II afferent fibers in muscle as well as cutaneous nerves. 4. Intracellular recordings from motoneurons of extensor carpi radialis revealed EPSPs following stimulation of hindlimb nerves with time courses corresponding to those of the facilitatory effects. We failed to detect any potential changes in the motoneurons of flexor carpi radialis following stimulation of hindlimb nerves.", "contents": "Ascending long spinal actions on forelimb motoneurons in the acute spinal cat. Ascending long spinal reflex system were investigated by means of monosynaptic reflex testing in the acutely spinalized unanesthetized cat. 1. Hindlimb nerve stimulation gave bilateral facilitatory effects on the motoneuron pools of pectoralis major and physiological flexors of the forelimb such as biceps brachii, extensor carpi radialis, extensor digitorum communis, but elicited depressive effects on the physiological extensors such as triceps brachii, flexor carpi radialis, flexor digitorum profundus. 2. In the latissimus dorsi, which is the antagonist of pectoralis major, a depressive effect was elicited by the stimulation of ipsilateral hindlimb nerves, and a facilitatory effect by contralateral stimulation. 3. These effects were evoked mainly from group II afferent fibers in muscle as well as cutaneous nerves. 4. Intracellular recordings from motoneurons of extensor carpi radialis revealed EPSPs following stimulation of hindlimb nerves with time courses corresponding to those of the facilitatory effects. We failed to detect any potential changes in the motoneurons of flexor carpi radialis following stimulation of hindlimb nerves."} {"id": "PMID:1253889", "title": "Photodegradable formulatins of DDT.", "content": "The incorporation of diphenylamine and diethylaniline in commercial DDT-WDP formulations sprayed on Phaseolus aureus and Tabernaemontana coronaria revealed that both these chemicals enhanced the initial rate of loss of DDT. Both these sensitizers exhibited no immediate adverse effect on the storage stability, pH, sieve requirement and colour of the formulations and introduced no phytotoxicity. Diphenylamine addition, however, had some adverse effects on the suspensibility.", "contents": "Photodegradable formulatins of DDT. The incorporation of diphenylamine and diethylaniline in commercial DDT-WDP formulations sprayed on Phaseolus aureus and Tabernaemontana coronaria revealed that both these chemicals enhanced the initial rate of loss of DDT. Both these sensitizers exhibited no immediate adverse effect on the storage stability, pH, sieve requirement and colour of the formulations and introduced no phytotoxicity. Diphenylamine addition, however, had some adverse effects on the suspensibility."} {"id": "PMID:1253890", "title": "A possible chemical basis for the higher mutagenicity of marijuana smoke as compared to tobacco smoke.", "content": "The results of comparative anslyses of polynuclear aromatic hydrocarbons in marijuana and tobacco smoke indicate a considerably higher content of potential carcinogens in the former. A model experiment involving delta9-tetrahydrocannabinol suggests that the pyrolysis products of cannabinoids are major contributors to the polynuclear aromatic hydrocarbons.", "contents": "A possible chemical basis for the higher mutagenicity of marijuana smoke as compared to tobacco smoke. The results of comparative anslyses of polynuclear aromatic hydrocarbons in marijuana and tobacco smoke indicate a considerably higher content of potential carcinogens in the former. A model experiment involving delta9-tetrahydrocannabinol suggests that the pyrolysis products of cannabinoids are major contributors to the polynuclear aromatic hydrocarbons."} {"id": "PMID:1253892", "title": "Double stranded ribonuclease activity in human lymphocyte nuclei.", "content": "Ribonuclease activity directed against the synthetic duplex polyrC:polyI was detected in nuclear extracts from both unstimulated and PHA-stimulated human lymphocytes. In the latter cells, the activity was about twice that of small lymphocytes.", "contents": "Double stranded ribonuclease activity in human lymphocyte nuclei. Ribonuclease activity directed against the synthetic duplex polyrC:polyI was detected in nuclear extracts from both unstimulated and PHA-stimulated human lymphocytes. In the latter cells, the activity was about twice that of small lymphocytes."} {"id": "PMID:1253893", "title": "Dissociation-constants of metat-ion-complexes with alkaline phosphatase from pig kidney.", "content": "Using metal-ion buffers it was possible to remove Zn2+, Mg2+ and Mn2+ ions of pig kidney alkaline phosphatase reversibly. The dissociation constants obtained are KEMg: 4 X 10(-7) M, KEMn: 4 X 10(-8) M and KEZn: 8 X 10(-13) M (22 degrees C, pH: 9.6, mu: 0.07).", "contents": "Dissociation-constants of metat-ion-complexes with alkaline phosphatase from pig kidney. Using metal-ion buffers it was possible to remove Zn2+, Mg2+ and Mn2+ ions of pig kidney alkaline phosphatase reversibly. The dissociation constants obtained are KEMg: 4 X 10(-7) M, KEMn: 4 X 10(-8) M and KEZn: 8 X 10(-13) M (22 degrees C, pH: 9.6, mu: 0.07)."} {"id": "PMID:1253895", "title": "Age and peritoneal fluid cellular distribution in women 20-40 years of age.", "content": "Cytologic aspiration specimens of peritoneal fluid revealed that mesothelial cell proportions were significantly reduced 19.2% in women between 26 and 35 years of age. Possibly, mesothelial cell renewal was decreased in women of the older age groups.", "contents": "Age and peritoneal fluid cellular distribution in women 20-40 years of age. Cytologic aspiration specimens of peritoneal fluid revealed that mesothelial cell proportions were significantly reduced 19.2% in women between 26 and 35 years of age. Possibly, mesothelial cell renewal was decreased in women of the older age groups."} {"id": "PMID:1253896", "title": "Biochemical markers in the taxonomy of the Actinomycetales.", "content": "Useful biochemical markers for the classification of Actinomycetales are: 1. DL- or LL-diaminopimelic acid in the peptidoglycan, 2. sugar composition of polysaccharides, 3. fatty acid spectrum of cell lipids. The occurrence of various kinds of branched fatty acids and of unsaturated fatty acids is of special value.", "contents": "Biochemical markers in the taxonomy of the Actinomycetales. Useful biochemical markers for the classification of Actinomycetales are: 1. DL- or LL-diaminopimelic acid in the peptidoglycan, 2. sugar composition of polysaccharides, 3. fatty acid spectrum of cell lipids. The occurrence of various kinds of branched fatty acids and of unsaturated fatty acids is of special value."} {"id": "PMID:1253897", "title": "Emericid, a new polyether antibiotic from Streptomyces hygroscopicus (DS 24 367).", "content": "Emericid is a new polyether polycyclic ionophore antibiotic excreted by Streptomyces hygroscopicus (DS 24 367). Active in vitro against Gram-positive bacteria, it is ineffective in vivo. At a 0.006-0.02% level in the diet it protects chickens and rabbits against coccidiosis.", "contents": "Emericid, a new polyether antibiotic from Streptomyces hygroscopicus (DS 24 367). Emericid is a new polyether polycyclic ionophore antibiotic excreted by Streptomyces hygroscopicus (DS 24 367). Active in vitro against Gram-positive bacteria, it is ineffective in vivo. At a 0.006-0.02% level in the diet it protects chickens and rabbits against coccidiosis."} {"id": "PMID:1253898", "title": "Cellular control of the tick-borne virus antigen production in persistently infected cell culture.", "content": "The influence of inhibition or stimulation of cellular DNA synthesis on tick-borne virus antigen production in persistently infected cell culture was studied. Either mitomycin C or cytosine-arabinoside caused cessation of antigen-containing cell number increase. Stimulation of cellular DNA synthesis by growth medium change increased the level of antigen-containing cells. When HEp-2-Sof culture was synchronized, a correlation was observed between the entrance of cells into DNA synthesis phase and the increase of proportion of antigen-containing cells.", "contents": "Cellular control of the tick-borne virus antigen production in persistently infected cell culture. The influence of inhibition or stimulation of cellular DNA synthesis on tick-borne virus antigen production in persistently infected cell culture was studied. Either mitomycin C or cytosine-arabinoside caused cessation of antigen-containing cell number increase. Stimulation of cellular DNA synthesis by growth medium change increased the level of antigen-containing cells. When HEp-2-Sof culture was synchronized, a correlation was observed between the entrance of cells into DNA synthesis phase and the increase of proportion of antigen-containing cells."} {"id": "PMID:1253899", "title": "Effect of air ionization of blood serotonin in vitro.", "content": "The effect of negative and positive air ionisation on siliconized blood serotonin was studied in vitro. The experiments showed that within 10 min positive ionisation increased serotonin levels in total blood (+40%), plasma (+90%), erythrocytes (+50%) and thrombocytes (+240%). On the other hand, negative ionization (10 min) lowered the serotonin content of total blood (-30%), plasma (-42.5%), erythrocytes (-41.7%) and thrombocytes (-72.3%), thus confirming the 'Krueger Effect' in vitro.", "contents": "Effect of air ionization of blood serotonin in vitro. The effect of negative and positive air ionisation on siliconized blood serotonin was studied in vitro. The experiments showed that within 10 min positive ionisation increased serotonin levels in total blood (+40%), plasma (+90%), erythrocytes (+50%) and thrombocytes (+240%). On the other hand, negative ionization (10 min) lowered the serotonin content of total blood (-30%), plasma (-42.5%), erythrocytes (-41.7%) and thrombocytes (-72.3%), thus confirming the 'Krueger Effect' in vitro."} {"id": "PMID:1253900", "title": "[Amino acid incorporation by human milk fat globules membranes (author's transl)].", "content": "Human milk fat globule membranes (MFGM) can incorporate radioactive 14C amino acids in a hot trichloracetic acid-insoluble material. Aspecific adsorption and bacterial contamination are unlikely. The products of protein synthesis were analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate or by action of proteolytic enzymes. Various inhibitors of protein synthesis were assayed. Fragments of rough endoplasmic reticulum or mitochondria could be involved in this incorporation.", "contents": "[Amino acid incorporation by human milk fat globules membranes (author's transl)]. Human milk fat globule membranes (MFGM) can incorporate radioactive 14C amino acids in a hot trichloracetic acid-insoluble material. Aspecific adsorption and bacterial contamination are unlikely. The products of protein synthesis were analyzed by polyacrylamide gel electrophoresis in sodium dodecyl sulfate or by action of proteolytic enzymes. Various inhibitors of protein synthesis were assayed. Fragments of rough endoplasmic reticulum or mitochondria could be involved in this incorporation."} {"id": "PMID:1253904", "title": "Alternative methods of animal sacrifice: the effect on intestinal function in vitro.", "content": "The total fluid uptake of everted sacs of rat jejunum was compared in animals killed by stunning and decapitation, or anaesthetised with ether. Fluid transport was significantly higher in the tissue prepared from stunned and decapitated animals. It is suggested that etherization may have adverse effects on the physiological viability of subsequently isolated tissues.", "contents": "Alternative methods of animal sacrifice: the effect on intestinal function in vitro. The total fluid uptake of everted sacs of rat jejunum was compared in animals killed by stunning and decapitation, or anaesthetised with ether. Fluid transport was significantly higher in the tissue prepared from stunned and decapitated animals. It is suggested that etherization may have adverse effects on the physiological viability of subsequently isolated tissues."} {"id": "PMID:1253905", "title": "Concerning the ionic basis of presynaptic inhibition.", "content": "The superfused rat cuneate nucleus has been used to investigate the sensitivity of primary afferent terminals and of evoked primary afferent depolarization (PAD) to alterations in extracellular K+ and Cl- ions levels. Results indicate that PAD is caused by an efflux of Cl- from primary afferent terminals rather than by an increase in extracellular K+.", "contents": "Concerning the ionic basis of presynaptic inhibition. The superfused rat cuneate nucleus has been used to investigate the sensitivity of primary afferent terminals and of evoked primary afferent depolarization (PAD) to alterations in extracellular K+ and Cl- ions levels. Results indicate that PAD is caused by an efflux of Cl- from primary afferent terminals rather than by an increase in extracellular K+."} {"id": "PMID:1253906", "title": "Effect of angiotensin II on neonatal lamb carotid arteries.", "content": "Isometric tension was measured in arterial strips from neonatal lambs and adult sheep, after stimulation by angiotensin II. During the early maturation period immediately following birth (3 weeks) there was a progressive increase in sensitivity to the agent.", "contents": "Effect of angiotensin II on neonatal lamb carotid arteries. Isometric tension was measured in arterial strips from neonatal lambs and adult sheep, after stimulation by angiotensin II. During the early maturation period immediately following birth (3 weeks) there was a progressive increase in sensitivity to the agent."} {"id": "PMID:1253909", "title": "Sodium pump: its importance to intercellular communication in heart fibres.", "content": "The effect of ouabain on the electrical coupling of canine Purkinje cells was investigated. It was found that the glycoside decreases cell communication through an increase in junctional resistance, what supports the view that the sodium pump has an important role on the control of cell communication.", "contents": "Sodium pump: its importance to intercellular communication in heart fibres. The effect of ouabain on the electrical coupling of canine Purkinje cells was investigated. It was found that the glycoside decreases cell communication through an increase in junctional resistance, what supports the view that the sodium pump has an important role on the control of cell communication."} {"id": "PMID:1253910", "title": "Behavior and endocrine effects of 3,4,5-trimethoxyamphetamine in male mice.", "content": "Effects of single doses of 50 and 100 mg/kg of TMA given i.p. were noted in male albino mice after 40 min and 2 1/2 h. Locomotor activity was significantly altered and biochemical tests indicated stimulatory effects on adrenocortical and adrenomedullary functions due to TMA.", "contents": "Behavior and endocrine effects of 3,4,5-trimethoxyamphetamine in male mice. Effects of single doses of 50 and 100 mg/kg of TMA given i.p. were noted in male albino mice after 40 min and 2 1/2 h. Locomotor activity was significantly altered and biochemical tests indicated stimulatory effects on adrenocortical and adrenomedullary functions due to TMA."} {"id": "PMID:1253911", "title": "Structure-activity relationships of cyclic acetylcholine analogues of the piperidinol and thiacyclohexanol series.", "content": "The hydrochlorides and methiodides of 1-methyl-3- and 4-acetoxypiperidine and their sulphonium analogues are cholinergic agonists. They are substrates for acetylcholinesterase. The sulphonium compounds have a 78(-524)-fold higher activity than its nitrogen analogues.", "contents": "Structure-activity relationships of cyclic acetylcholine analogues of the piperidinol and thiacyclohexanol series. The hydrochlorides and methiodides of 1-methyl-3- and 4-acetoxypiperidine and their sulphonium analogues are cholinergic agonists. They are substrates for acetylcholinesterase. The sulphonium compounds have a 78(-524)-fold higher activity than its nitrogen analogues."} {"id": "PMID:1253913", "title": "The accumulation pattern of ingested gossypol in selected organs of the rat.", "content": "Bound gossypol levels in the spleen and kidney of rats ingesting dietary gossypol (0.98%) varied directly with the feeding intervals of 6, 14, 28 and 35 days. Free gossypol level in the kidney, spleen and lungs increased for 14 days and then tended to decrease as the feeding period was extended.", "contents": "The accumulation pattern of ingested gossypol in selected organs of the rat. Bound gossypol levels in the spleen and kidney of rats ingesting dietary gossypol (0.98%) varied directly with the feeding intervals of 6, 14, 28 and 35 days. Free gossypol level in the kidney, spleen and lungs increased for 14 days and then tended to decrease as the feeding period was extended."} {"id": "PMID:1253914", "title": "Interaction of atropine or methylatropinium with four effects of two cholinergic drugs.", "content": "In mice, pilocarpine - or oxotremorine - induced decrease in locomotor activity and increase of the reaction time to pain were antagonized by atropine and not by methylatropinium. Identical doses of atropine and methylatropinium suppressed the antagonism of the cholinergics towards reserpine-induced palpebral ptosis. Cholinergics-induced hypothermia was not clearly antagonized by atropine or methylatropinium.", "contents": "Interaction of atropine or methylatropinium with four effects of two cholinergic drugs. In mice, pilocarpine - or oxotremorine - induced decrease in locomotor activity and increase of the reaction time to pain were antagonized by atropine and not by methylatropinium. Identical doses of atropine and methylatropinium suppressed the antagonism of the cholinergics towards reserpine-induced palpebral ptosis. Cholinergics-induced hypothermia was not clearly antagonized by atropine or methylatropinium."} {"id": "PMID:1253915", "title": "Melatonin antagonizes colchicine-induced mitotic arrest.", "content": "Melatonin, in concentrations up to 10(-3) M, showed no effect on mitosis in cultures of HeLa or KB cells. However, when melatonin at 10(-4) M was preincubated with HeLa cells prior to addition of 10(-7) M colchicine, a reduction in the mitotic index, in comparison to colchicine alone, was observed.", "contents": "Melatonin antagonizes colchicine-induced mitotic arrest. Melatonin, in concentrations up to 10(-3) M, showed no effect on mitosis in cultures of HeLa or KB cells. However, when melatonin at 10(-4) M was preincubated with HeLa cells prior to addition of 10(-7) M colchicine, a reduction in the mitotic index, in comparison to colchicine alone, was observed."} {"id": "PMID:1253917", "title": "Extrachromosomal DNA and RNA-synthesis in oocytes of Creophilus maxillosus (Staphylinidae, Coleoptera, Polyphaga).", "content": "It has been found that the transcriptional activity of nuclear extra DNA in Creophilus maxillosus oocytes, as examined by autoradiography, increases parallel with its dispersion during the previtellogenic period of oocyte growth. The RNA, after being synthesized in the greatly enlarged oocyte nucleus, is subsequently transported into the cytoplasm. The oocyte chromosomes form a karyosphere and synthesize the RNA more weakly than other parts of the nucleus, which contain the extra DNA in a highly dispersed condition.", "contents": "Extrachromosomal DNA and RNA-synthesis in oocytes of Creophilus maxillosus (Staphylinidae, Coleoptera, Polyphaga). It has been found that the transcriptional activity of nuclear extra DNA in Creophilus maxillosus oocytes, as examined by autoradiography, increases parallel with its dispersion during the previtellogenic period of oocyte growth. The RNA, after being synthesized in the greatly enlarged oocyte nucleus, is subsequently transported into the cytoplasm. The oocyte chromosomes form a karyosphere and synthesize the RNA more weakly than other parts of the nucleus, which contain the extra DNA in a highly dispersed condition."} {"id": "PMID:1253918", "title": "The distribution of endocrine-like cells in the human male and female urethral epithelium.", "content": "Histochemical and electron microscopic techniques have been used to study the nature and distribution of fluorescent, endocrine-like cells in the urethra of the human male and female. The confinement of such cells to specific regions of the urethra is discussed in relation to the embryological development of this part of the urinary tract.", "contents": "The distribution of endocrine-like cells in the human male and female urethral epithelium. Histochemical and electron microscopic techniques have been used to study the nature and distribution of fluorescent, endocrine-like cells in the urethra of the human male and female. The confinement of such cells to specific regions of the urethra is discussed in relation to the embryological development of this part of the urinary tract."} {"id": "PMID:1253920", "title": "Cytochemical evidence for stage-specific changes of nuclear RNA and nonhistone protein content during early development of Triturus vulgaris.", "content": "During early embryogenesis of Triturus vulgaris, RNA and nonhistone protein contents of neuroectoderm nuclei change with stage specifically. Maximum values were found in the late gastrula after embryonic induction, and in the late neurula with the formation of the neural tube. The stage-specific increases of RNA and nonhistone protein are correlated with a preceding increase of Feulgen-DNA content.", "contents": "Cytochemical evidence for stage-specific changes of nuclear RNA and nonhistone protein content during early development of Triturus vulgaris. During early embryogenesis of Triturus vulgaris, RNA and nonhistone protein contents of neuroectoderm nuclei change with stage specifically. Maximum values were found in the late gastrula after embryonic induction, and in the late neurula with the formation of the neural tube. The stage-specific increases of RNA and nonhistone protein are correlated with a preceding increase of Feulgen-DNA content."} {"id": "PMID:1253921", "title": "Coated vesicles in the rat adrenal glomerular zone after a low-sodium diet.", "content": "In rats subjected to a low-sodium diet, a great activity was observed of the coated vesicles at Golgi complex and cell surfaces of glomerular adrenal zone. These findings are related to the function of these organoids in the uptake and transport of necessary substances under stimulating conditions of the zone.", "contents": "Coated vesicles in the rat adrenal glomerular zone after a low-sodium diet. In rats subjected to a low-sodium diet, a great activity was observed of the coated vesicles at Golgi complex and cell surfaces of glomerular adrenal zone. These findings are related to the function of these organoids in the uptake and transport of necessary substances under stimulating conditions of the zone."} {"id": "PMID:1253922", "title": "Effect of haemolysis on plasms and serum immunoglobulin estimations.", "content": "Plasma IgG, IgM and IgA estimations were carried out in blood samples with varying degrees of haemolysis, produced by controlled ultrasonication. Extent of haemolysis was determined by plasma haemoglobin, plasma potassium and packed cell volume; and plasma IgG, IgM and IgA estimations showed a steady and significant fall with increasing haemolysis. A calculated correction is proposed which compensates for the dilutional effect of haemolysis, during estimations of plasma and serum immunoglobulins.", "contents": "Effect of haemolysis on plasms and serum immunoglobulin estimations. Plasma IgG, IgM and IgA estimations were carried out in blood samples with varying degrees of haemolysis, produced by controlled ultrasonication. Extent of haemolysis was determined by plasma haemoglobin, plasma potassium and packed cell volume; and plasma IgG, IgM and IgA estimations showed a steady and significant fall with increasing haemolysis. A calculated correction is proposed which compensates for the dilutional effect of haemolysis, during estimations of plasma and serum immunoglobulins."} {"id": "PMID:1253924", "title": "Undulating tubules in lymphocytes of an apparently healthy human donor.", "content": "So-called 'undulating tubules' were found in the blood lymphocytes of an apparently healthy 33-year-old male. Undulating tubules have been noted to occur frequently in kidney cells and blood lymphocytes of patients suffering from collagen diseases and especially from SLE. They have been suggested to be a possibly pathognomonic finding in such diseases. Our result seems to contradict such an association.", "contents": "Undulating tubules in lymphocytes of an apparently healthy human donor. So-called 'undulating tubules' were found in the blood lymphocytes of an apparently healthy 33-year-old male. Undulating tubules have been noted to occur frequently in kidney cells and blood lymphocytes of patients suffering from collagen diseases and especially from SLE. They have been suggested to be a possibly pathognomonic finding in such diseases. Our result seems to contradict such an association."} {"id": "PMID:1253926", "title": "Effect of estradiol on aminoacid incorporation into proteins of different hypothalamic areas in prepuberal rats.", "content": "Estradiol in vitro produces a significant increase in the incorporation of 3H-leucine into proteins of the anterior hypothalamic area in prepuberal female rats, 15 and 20 days old, but not in younger animals. The ovarian hormone induced no changes in the protein synthetic activity of middle and posterior hypothalamus and cerebral cortex in prepuberal female rats of different ages. Estradiol did not modify the protein synthesis of the hypothalamus and cerebral cortex in prepuberal male rats.", "contents": "Effect of estradiol on aminoacid incorporation into proteins of different hypothalamic areas in prepuberal rats. Estradiol in vitro produces a significant increase in the incorporation of 3H-leucine into proteins of the anterior hypothalamic area in prepuberal female rats, 15 and 20 days old, but not in younger animals. The ovarian hormone induced no changes in the protein synthetic activity of middle and posterior hypothalamus and cerebral cortex in prepuberal female rats of different ages. Estradiol did not modify the protein synthesis of the hypothalamus and cerebral cortex in prepuberal male rats."} {"id": "PMID:1253927", "title": "Effect of the extracts from Aristolochia indica Linn. on interception in female mice.", "content": "The crude petroleum ether, chloroform and alcoholic extracts from the roots of Aristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used.", "contents": "Effect of the extracts from Aristolochia indica Linn. on interception in female mice. The crude petroleum ether, chloroform and alcoholic extracts from the roots of Aristolochia indica (Linn.) showed 100% interceptive activity in mature female mice at the single dose of 100 mg/kg body wt. The follow-up studies with the chloroform extract showed the most significant effect in the basic part and two acidic fractions at the single dose levels of 50 mg/kg body wt. No toxic effect was observed at the dose levels used."} {"id": "PMID:1253928", "title": "Granulocyte colony formation in vitro: enhancement by human placental (umbilical cord) serum.", "content": "Addition of human placental umbilical cord serum to bone marrow cultures reproducibly increased the number of granulocyte colonies in vitro. This stimulatory effect was significantly greater than that of fetal calf serum which was seen in cultures of human bone marrow under the conditions described.", "contents": "Granulocyte colony formation in vitro: enhancement by human placental (umbilical cord) serum. Addition of human placental umbilical cord serum to bone marrow cultures reproducibly increased the number of granulocyte colonies in vitro. This stimulatory effect was significantly greater than that of fetal calf serum which was seen in cultures of human bone marrow under the conditions described."} {"id": "PMID:1253960", "title": "[Influence of immobilization and 3(beta-aminoethyl)-1, 2, 4-triazole on the calcium level in the tissues of the stomach of guinea pigs during the formation of experimental ulcers].", "content": "The Ca2+ ions content in the blood plasma and gastric tissues of guinea pigs during experimental ulceration provoked by a 12-hour immobilation or through introduction of 3(beta-aminoethyl)-1,2,4-triazol--a histamine analogue--was measured by using atom absorption spectrophotometry. A sharp fall in the concentration of calcium in gastric tissues upon immobilization down to 79 per cent (317 gamma/g) and after administration of the histamine analogue--down to 71 per cent (287 gamma/g. Similar shifts were seen to occur in the blood plasma as well. According to the authors this implies that under the effect of different action the tissular dystrophy develops by following a common mechanism with involvement not only of the adenylcyclase system, but of the calcium ions metabolism as well.", "contents": "[Influence of immobilization and 3(beta-aminoethyl)-1, 2, 4-triazole on the calcium level in the tissues of the stomach of guinea pigs during the formation of experimental ulcers]. The Ca2+ ions content in the blood plasma and gastric tissues of guinea pigs during experimental ulceration provoked by a 12-hour immobilation or through introduction of 3(beta-aminoethyl)-1,2,4-triazol--a histamine analogue--was measured by using atom absorption spectrophotometry. A sharp fall in the concentration of calcium in gastric tissues upon immobilization down to 79 per cent (317 gamma/g) and after administration of the histamine analogue--down to 71 per cent (287 gamma/g. Similar shifts were seen to occur in the blood plasma as well. According to the authors this implies that under the effect of different action the tissular dystrophy develops by following a common mechanism with involvement not only of the adenylcyclase system, but of the calcium ions metabolism as well."} {"id": "PMID:1253963", "title": "[Synthesis of analogues of acetohydroxam lacetic acid with phytotoxic activity].", "content": "Syntheses, spectroscopic data and phytotoxic activities of some N-acyl-O-alkylhydroxylamines, similar in structure to the natural compoud, methyl acetohydroxamyl acetate, are reported. Many of synthesized compounds show strong growth-inhibiting activity on both roots and coleoptiles of Triticum vulgare seedlings.", "contents": "[Synthesis of analogues of acetohydroxam lacetic acid with phytotoxic activity]. Syntheses, spectroscopic data and phytotoxic activities of some N-acyl-O-alkylhydroxylamines, similar in structure to the natural compoud, methyl acetohydroxamyl acetate, are reported. Many of synthesized compounds show strong growth-inhibiting activity on both roots and coleoptiles of Triticum vulgare seedlings."} {"id": "PMID:1253964", "title": "Preparation and spectroscopic behavior of acetylderivatives of sulphonamides.", "content": "Acetylderivatives of five sulpha drugs (N1-phenylsulphamilamide, sulphapyridine, sulphapyrimidine, sulphamerazine, sulphamethazine) and of three reference compounds, devoid of the para amino group, are synthetized. The trends of the U.V. spectra and of the symmetric stretching frequency of the SO2 group of the prepared compounds are described and discussed in a systematic way, by means of a simple conjugation model. Our data show that, on the basis of the values of the indices of electronic structure [upsilons(SO2), lambdap], the N1-acetylderivatives would appear to have a lower bacteriostatic activity than that of the non-acetylated compounds, which is in disagreement with the literature. The question therefore arises as to whether the N1-acetylderivatives are to be considered an exception to the structure-activity correlations previously put forward, or whether, owing to phenomena of hydrolysis, the degree of activity can no longer be attributed to the form characterized by the indices measured.", "contents": "Preparation and spectroscopic behavior of acetylderivatives of sulphonamides. Acetylderivatives of five sulpha drugs (N1-phenylsulphamilamide, sulphapyridine, sulphapyrimidine, sulphamerazine, sulphamethazine) and of three reference compounds, devoid of the para amino group, are synthetized. The trends of the U.V. spectra and of the symmetric stretching frequency of the SO2 group of the prepared compounds are described and discussed in a systematic way, by means of a simple conjugation model. Our data show that, on the basis of the values of the indices of electronic structure [upsilons(SO2), lambdap], the N1-acetylderivatives would appear to have a lower bacteriostatic activity than that of the non-acetylated compounds, which is in disagreement with the literature. The question therefore arises as to whether the N1-acetylderivatives are to be considered an exception to the structure-activity correlations previously put forward, or whether, owing to phenomena of hydrolysis, the degree of activity can no longer be attributed to the form characterized by the indices measured."} {"id": "PMID:1253965", "title": "2,6-dialkylpiperazines. VII-Synthesis of N4-(2'-pyridyl)-2,6-dimethylpiperazine and separation of its geometrical isomers.", "content": "Cis-(I a) and trans-(I b) N4-(2'-pyridyl)-2,6-dimethylpiperazine were synthetised as the key intermediates for isomeric 2,6-dimethylpiperazine derivatives to be pharmacologically tested.", "contents": "2,6-dialkylpiperazines. VII-Synthesis of N4-(2'-pyridyl)-2,6-dimethylpiperazine and separation of its geometrical isomers. Cis-(I a) and trans-(I b) N4-(2'-pyridyl)-2,6-dimethylpiperazine were synthetised as the key intermediates for isomeric 2,6-dimethylpiperazine derivatives to be pharmacologically tested."} {"id": "PMID:1253962", "title": "[Influence of octadine, reserpine and methyl-dopa on the hemodynamic system].", "content": "In experiments set up on rats the influence of octadine (sanotensin), reserpine and methyl-dopa on the basic characteristics of the systemic hemodynamics in persistent renovascular hypertension was studied. The nature of the influence exerted by the above drugs on the systemic hemodynamics of hypertensive rats is shown to depend upon the duration of their action on the organism. The hypotensive effect manifests itself first by reduced cardiac ejection and then by a fall of the total peripheral resistance. It is presumed that the disappearance of the inhibitory action of octadine, reserpine and methyl-dopa on the cardiac ejection is related to the development of a compensatory reaction aimed at maintaining the needed level of the blood supply to the organs and tissues--i. e. at \"systemic autoregulation\".", "contents": "[Influence of octadine, reserpine and methyl-dopa on the hemodynamic system]. In experiments set up on rats the influence of octadine (sanotensin), reserpine and methyl-dopa on the basic characteristics of the systemic hemodynamics in persistent renovascular hypertension was studied. The nature of the influence exerted by the above drugs on the systemic hemodynamics of hypertensive rats is shown to depend upon the duration of their action on the organism. The hypotensive effect manifests itself first by reduced cardiac ejection and then by a fall of the total peripheral resistance. It is presumed that the disappearance of the inhibitory action of octadine, reserpine and methyl-dopa on the cardiac ejection is related to the development of a compensatory reaction aimed at maintaining the needed level of the blood supply to the organs and tissues--i. e. at \"systemic autoregulation\"."} {"id": "PMID:1253966", "title": "Alkylthiophenylureas with phytotoxic activity.", "content": "A series of 1-(p.alkylthio)phenylureas variously substituted on the N atom in position 3 (substances I leads to XXXVII) has been prepared and studied for pre- and post-emergence phytotoxicity. Some compounds were found to have high activity; in particular some 1-(p.alkylthio)phenyl-3-dimethylureas showed high activity even at very low doses (2 kg/ha).", "contents": "Alkylthiophenylureas with phytotoxic activity. A series of 1-(p.alkylthio)phenylureas variously substituted on the N atom in position 3 (substances I leads to XXXVII) has been prepared and studied for pre- and post-emergence phytotoxicity. Some compounds were found to have high activity; in particular some 1-(p.alkylthio)phenyl-3-dimethylureas showed high activity even at very low doses (2 kg/ha)."} {"id": "PMID:1253967", "title": "[Research on heterocyclic compounds. II.- Imidazo ( 1,2-a) pyridin-2-acetic acids].", "content": "A series of ethyl imidazo [1,2-a]pyridin-2-acetates was prepared by reaction between several substituted 2-aminopyridines and ethyl-4-bromoacetate. From these esters the corresponding acids were prepared and their anti-inflammatory activity was tested.", "contents": "[Research on heterocyclic compounds. II.- Imidazo ( 1,2-a) pyridin-2-acetic acids]. A series of ethyl imidazo [1,2-a]pyridin-2-acetates was prepared by reaction between several substituted 2-aminopyridines and ethyl-4-bromoacetate. From these esters the corresponding acids were prepared and their anti-inflammatory activity was tested."} {"id": "PMID:1253968", "title": "Cholinergic compounds VII - Synthesis and pharmacological activity of some trimethylammonium iodides related to desethermuscarine.", "content": "Some substances similar to desethermuscarine were synthesized and studied as cholinergics on isolated organs. The results show the importance of the cyclopentane nucleus with regard to activity. The activity of 3-methyltrimethylammonium hexane iodide is particularly interesting for, though lacking the oxygenated function in 3 and having a different methyl spatial arrangement, this compound is only ten times less active than desethermuscarone.", "contents": "Cholinergic compounds VII - Synthesis and pharmacological activity of some trimethylammonium iodides related to desethermuscarine. Some substances similar to desethermuscarine were synthesized and studied as cholinergics on isolated organs. The results show the importance of the cyclopentane nucleus with regard to activity. The activity of 3-methyltrimethylammonium hexane iodide is particularly interesting for, though lacking the oxygenated function in 3 and having a different methyl spatial arrangement, this compound is only ten times less active than desethermuscarone."} {"id": "PMID:1253969", "title": "Determination of structure-activity relationships of 2-aryl-1,3-indandiones.", "content": "The uncoupling activities in rat liver mitochondria of a number of 2-aryl-1,3-indandiones were studied by means of the Free-Wilson method followed by a stepwise regression analysis. The activity appears to be mainly dependent on the hydrophobic parameter.", "contents": "Determination of structure-activity relationships of 2-aryl-1,3-indandiones. The uncoupling activities in rat liver mitochondria of a number of 2-aryl-1,3-indandiones were studied by means of the Free-Wilson method followed by a stepwise regression analysis. The activity appears to be mainly dependent on the hydrophobic parameter."} {"id": "PMID:1254022", "title": "Laparoscopic sterilization with electrocautery, spring-loaded clips, and Silastic bands: technical problems and early complications.", "content": "Among 2283 patients, rates of technical failure, technical difficulty, and operative and early postoperative complications were evaluated for different methods of tubal occlusion at laparoscopy: electrocoagulation (980 cases), spring-loaded clip application (991 cases), and Silastic band application (312 cases). Rates of technical failure and technical difficulty at surgery were significantly higher (P less than 0.05) for the spring-loaded clip technique than for the electrocoagulation and Silastic band techniques. Mechanical and optical difficulties with the prototype spring clip applicator were the major sources of technical difficulties. Rates of operative (1.2%) and early postoperative (1.9%) complications were not significantly different for the three techniques of tubal occlusion. It is concluded that all three study techniques appear to be practical, and large, long-term, randomized, comparative studies to determine rates of failure and subsequent gynecologic problems are necessary to determine the best method of sterilization.", "contents": "Laparoscopic sterilization with electrocautery, spring-loaded clips, and Silastic bands: technical problems and early complications. Among 2283 patients, rates of technical failure, technical difficulty, and operative and early postoperative complications were evaluated for different methods of tubal occlusion at laparoscopy: electrocoagulation (980 cases), spring-loaded clip application (991 cases), and Silastic band application (312 cases). Rates of technical failure and technical difficulty at surgery were significantly higher (P less than 0.05) for the spring-loaded clip technique than for the electrocoagulation and Silastic band techniques. Mechanical and optical difficulties with the prototype spring clip applicator were the major sources of technical difficulties. Rates of operative (1.2%) and early postoperative (1.9%) complications were not significantly different for the three techniques of tubal occlusion. It is concluded that all three study techniques appear to be practical, and large, long-term, randomized, comparative studies to determine rates of failure and subsequent gynecologic problems are necessary to determine the best method of sterilization."} {"id": "PMID:1254023", "title": "Some gross observations of the epididymides following vasectomy: a clinical study.", "content": "In 114 vasectomized men, 220 epididymides were grossly examined during vasovasostomy. Fullness, distention, turgidity, thickening, induration, and other gross changes of the epididymides, including the formation of cystic spermatic granuloma, or spermatocele, indicated inadequate removal of spermatozoa and testicular fluid from the sequestrated proximal seminal ducts and the epididymis. Further studies are necessary to determine whether the epididymal changes following vasectomy have any effect on sperm morphology and sperm physiology. The information obtained from these studies possibly may explain the poor pregnancy rates in the spouses of successfully vasanastomosed patients.", "contents": "Some gross observations of the epididymides following vasectomy: a clinical study. In 114 vasectomized men, 220 epididymides were grossly examined during vasovasostomy. Fullness, distention, turgidity, thickening, induration, and other gross changes of the epididymides, including the formation of cystic spermatic granuloma, or spermatocele, indicated inadequate removal of spermatozoa and testicular fluid from the sequestrated proximal seminal ducts and the epididymis. Further studies are necessary to determine whether the epididymal changes following vasectomy have any effect on sperm morphology and sperm physiology. The information obtained from these studies possibly may explain the poor pregnancy rates in the spouses of successfully vasanastomosed patients."} {"id": "PMID:1254024", "title": "Anatomical sizes of the human vas deferens after vasectomy.", "content": "After vasectomy, the lumen of the testicular side of the vas deferens dilates, apparently because of internal pressure from accumulation of spermatic fluid. This dilatation occurs within the 1st postoperative year. It causes a thinning of the wall of the vas without significant increase in the external diameter. The extent of dilatation is similar in the same man, but differs markedly between individuals, the mean increase in diameter being approximately 70%. The implications of this difference in size are discussed with regard to vas anastomosis and to the possible use of devices to rejoin the vas or to bridge a defect created by a prior vasectomy.", "contents": "Anatomical sizes of the human vas deferens after vasectomy. After vasectomy, the lumen of the testicular side of the vas deferens dilates, apparently because of internal pressure from accumulation of spermatic fluid. This dilatation occurs within the 1st postoperative year. It causes a thinning of the wall of the vas without significant increase in the external diameter. The extent of dilatation is similar in the same man, but differs markedly between individuals, the mean increase in diameter being approximately 70%. The implications of this difference in size are discussed with regard to vas anastomosis and to the possible use of devices to rejoin the vas or to bridge a defect created by a prior vasectomy."} {"id": "PMID:1254026", "title": "Comparison of the tray agglutination technique with the gelatin agglutination technique for the detection of spermagglutinating activity in human sera.", "content": "Extensive comparisons were made between the tray agglutination test (TAT) and the gelatin agglutination test (GAT) in order to evaluate the validity of the TAT for demonstrating spermagglutinating activity in human sera. The incidence of spermagglutination in both tests was about the same. In screening 118 samples from infertile men and women, the TAT seemed to be more sensitive, whereas the reverse was true when 143 samples earlier found positive with the GAT were tested. These differences were mainly encountered with low titers. Two T-agglutinating sera (or 2% of the sera) with a GAT titer of 16 or more (both had a titer of 64) were missed with the TAT. On the other hand, two sera (or 2% of the screened samples) having small H-agglutinates up to a titer of 32 to 64 were positive only with the TAT.", "contents": "Comparison of the tray agglutination technique with the gelatin agglutination technique for the detection of spermagglutinating activity in human sera. Extensive comparisons were made between the tray agglutination test (TAT) and the gelatin agglutination test (GAT) in order to evaluate the validity of the TAT for demonstrating spermagglutinating activity in human sera. The incidence of spermagglutination in both tests was about the same. In screening 118 samples from infertile men and women, the TAT seemed to be more sensitive, whereas the reverse was true when 143 samples earlier found positive with the GAT were tested. These differences were mainly encountered with low titers. Two T-agglutinating sera (or 2% of the sera) with a GAT titer of 16 or more (both had a titer of 64) were missed with the TAT. On the other hand, two sera (or 2% of the screened samples) having small H-agglutinates up to a titer of 32 to 64 were positive only with the TAT."} {"id": "PMID:1254027", "title": "Some properties of human endometrial alkaline phosphatase.", "content": "A study of some biochemical properties of alkaline phosphatase derived from human endometrium has been undertaken. The endometrial enzyme has been shown to be different from alkaline phosphatases obtained from placenta and small intestine. Endometrial alkaline phosphatase is inhibited by sodium deoxycholate but not by L-phenylalanine; it is completely inhibited by 3 M urea. Magnesium ions have no significant effect on the endometrial enzyme. No differences in biochemical properties were observed when alkaline phosphatase from follicular phase endometrium was compared with that from luteal phase tissue. Acrylamide gel electrophoresis showed a single, constant band of enzyme at all stages of the cycle. It is concluded that, despite the cyclic appearance of alkaline phosphatase in endometrial glands and the constant presence of the enzyme in blood vessels, there is but one variety of alkaline phosphatase in human endometrium.", "contents": "Some properties of human endometrial alkaline phosphatase. A study of some biochemical properties of alkaline phosphatase derived from human endometrium has been undertaken. The endometrial enzyme has been shown to be different from alkaline phosphatases obtained from placenta and small intestine. Endometrial alkaline phosphatase is inhibited by sodium deoxycholate but not by L-phenylalanine; it is completely inhibited by 3 M urea. Magnesium ions have no significant effect on the endometrial enzyme. No differences in biochemical properties were observed when alkaline phosphatase from follicular phase endometrium was compared with that from luteal phase tissue. Acrylamide gel electrophoresis showed a single, constant band of enzyme at all stages of the cycle. It is concluded that, despite the cyclic appearance of alkaline phosphatase in endometrial glands and the constant presence of the enzyme in blood vessels, there is but one variety of alkaline phosphatase in human endometrium."} {"id": "PMID:1254028", "title": "Studies of rabbit ovarian contractility using chronically implanted transducers.", "content": "A chronically implanted, highly sensitive force transducer was used to study ovarian contractions in the rabbit. The transducer is implanted into the medulla of the ovary through its long axis. The leads are then drawn through the abdominal wall and directed subcutaneously to the back of the neck. The miniature pin connector is fixed into place beneath the skin to facilitate accessibility for repeated recordings, obviating the necessity for anesthesia or serial laparotomies. Intraovarian transducers were implanted in isolated rabbits. Serial recordings of ovarian contractions were made at weekly intervals for 3 weeks, following which ovulation was induced with 100 IU of human chorionic gonadotropin (HCG). Extended recordings were made from 3 through 13 hours after HCG administration to six animals. Recordings revealed increased ovarian contractile activity beginning just before the anticipated time of ovulation. The observations support those of previous acute experiments and demonstrate a relationship between ovarian contractile activity and the process of follicle rupture.", "contents": "Studies of rabbit ovarian contractility using chronically implanted transducers. A chronically implanted, highly sensitive force transducer was used to study ovarian contractions in the rabbit. The transducer is implanted into the medulla of the ovary through its long axis. The leads are then drawn through the abdominal wall and directed subcutaneously to the back of the neck. The miniature pin connector is fixed into place beneath the skin to facilitate accessibility for repeated recordings, obviating the necessity for anesthesia or serial laparotomies. Intraovarian transducers were implanted in isolated rabbits. Serial recordings of ovarian contractions were made at weekly intervals for 3 weeks, following which ovulation was induced with 100 IU of human chorionic gonadotropin (HCG). Extended recordings were made from 3 through 13 hours after HCG administration to six animals. Recordings revealed increased ovarian contractile activity beginning just before the anticipated time of ovulation. The observations support those of previous acute experiments and demonstrate a relationship between ovarian contractile activity and the process of follicle rupture."} {"id": "PMID:1254029", "title": "The sperm-cervical mucus contact test: a preliminary report.", "content": "Infertility in men and women with spermagglutinins is the result of disturbed penetration and migration of spermatozoa in the cervical mucus. In ejaculates with partial spermagglutination caused by autoimmunization, the progressive propulsion of the sperm was changed into stationary, shaking movement the moment the sperm came into contact with cervical mucus. The same alteration in spermatozoal motility pattern also occurred when spermatozoa from a normal, fertile ejaculate came into contact with cervical mucus of a woman whose serum contained sperm antibodies. This shaking phenomenon was visualized in a simple test, the sperm-cervical mucus contact test. We demonstrated that sensitized spermatozoa exhibit the shaking phenomenon after contact with the glycoprotein fraction of the cervical mucus and not after contact with the aqueous fraction. Therefore, the hypothesis is introduced that the shaking phenomenon is due to an interaction between sensitized spermatozoa and the glycoprotein micelles in cervical mucus.", "contents": "The sperm-cervical mucus contact test: a preliminary report. Infertility in men and women with spermagglutinins is the result of disturbed penetration and migration of spermatozoa in the cervical mucus. In ejaculates with partial spermagglutination caused by autoimmunization, the progressive propulsion of the sperm was changed into stationary, shaking movement the moment the sperm came into contact with cervical mucus. The same alteration in spermatozoal motility pattern also occurred when spermatozoa from a normal, fertile ejaculate came into contact with cervical mucus of a woman whose serum contained sperm antibodies. This shaking phenomenon was visualized in a simple test, the sperm-cervical mucus contact test. We demonstrated that sensitized spermatozoa exhibit the shaking phenomenon after contact with the glycoprotein fraction of the cervical mucus and not after contact with the aqueous fraction. Therefore, the hypothesis is introduced that the shaking phenomenon is due to an interaction between sensitized spermatozoa and the glycoprotein micelles in cervical mucus."} {"id": "PMID:1254051", "title": "[An analysis of the electrical responses of the neocortex evoked by stimulation of different hypothalamic structures].", "content": "Evoked potentials and extracellular spike activity during stimulation of the posterior, lateral, anterior, and ventro-medical hypothalamus were recorded in different areas of the neocortex in unanesthetized cats. Hypothalamo--cortical evoked potentials (HC EP) of maximal amplitude are generated in gyr. sigm. ant. with 0.5--2.5 msec latency. The responses are of positive--negative configuration and often a fast spike--like defiction appears at the positive phase. EP in gyr. suprasylv. med. are initially negative and of 2--6 msec latency. Most effective is stimulation of the posterior and lateral hypothalamus, HC EP in gyr. sigm. ant. following the frequency of stimulation up to 200/sec and being characterized not only by a high \"functional lability\" or reproducibility but also by the ability of posttetanic potentiation. With the aid of paired stimuli, the early fast component of the EP in the sensorimotor cortex was shown to appear at an interval of approximately 2 msec. HC EP entirely recover 50--150 msec after the conditioning stimulus. The recovery cycle is biphasic and reflect, a biphasic change of the excitability of neurons in gyr. sigm. ant. and suprasylvian associative areas of the cortex. The latency of evoked discharges of some neurons of the sensorimotor cortex during stimulation of the posterior hypothalamus, is 0.8--1.5 msec, which suggests the existence of a monosynaptic pathway for the hypothalamo--cortical discharges. The maximal amount of neurons in deep layers of gyr. sigm. ant. respond during development of the early and the main positive deflections of HC EP.", "contents": "[An analysis of the electrical responses of the neocortex evoked by stimulation of different hypothalamic structures]. Evoked potentials and extracellular spike activity during stimulation of the posterior, lateral, anterior, and ventro-medical hypothalamus were recorded in different areas of the neocortex in unanesthetized cats. Hypothalamo--cortical evoked potentials (HC EP) of maximal amplitude are generated in gyr. sigm. ant. with 0.5--2.5 msec latency. The responses are of positive--negative configuration and often a fast spike--like defiction appears at the positive phase. EP in gyr. suprasylv. med. are initially negative and of 2--6 msec latency. Most effective is stimulation of the posterior and lateral hypothalamus, HC EP in gyr. sigm. ant. following the frequency of stimulation up to 200/sec and being characterized not only by a high \"functional lability\" or reproducibility but also by the ability of posttetanic potentiation. With the aid of paired stimuli, the early fast component of the EP in the sensorimotor cortex was shown to appear at an interval of approximately 2 msec. HC EP entirely recover 50--150 msec after the conditioning stimulus. The recovery cycle is biphasic and reflect, a biphasic change of the excitability of neurons in gyr. sigm. ant. and suprasylvian associative areas of the cortex. The latency of evoked discharges of some neurons of the sensorimotor cortex during stimulation of the posterior hypothalamus, is 0.8--1.5 msec, which suggests the existence of a monosynaptic pathway for the hypothalamo--cortical discharges. The maximal amount of neurons in deep layers of gyr. sigm. ant. respond during development of the early and the main positive deflections of HC EP."} {"id": "PMID:1254052", "title": "[Neuronal organization of the thermosensory region of the anterior hypothalamus].", "content": "In anesthetized rabbits, extracellular recording of activity of 236 neurons was made in the anterior hypothalamus on changing of its temperature (+/-3 degrees C). 27% of the neurons revealed high sensitivity to the temperature stimulus with coefficient Q10 from 2.4 to 30; 6% of the neurons reacted by the on-response type; 5% of the neurons changed their activity and preserved the new level. The character of the unit responses seems to indicate that the anterior hypothalamus fulfills not only the reception of temperature shifts, i.e. the primary processing of information, but its further analysis as well.", "contents": "[Neuronal organization of the thermosensory region of the anterior hypothalamus]. In anesthetized rabbits, extracellular recording of activity of 236 neurons was made in the anterior hypothalamus on changing of its temperature (+/-3 degrees C). 27% of the neurons revealed high sensitivity to the temperature stimulus with coefficient Q10 from 2.4 to 30; 6% of the neurons reacted by the on-response type; 5% of the neurons changed their activity and preserved the new level. The character of the unit responses seems to indicate that the anterior hypothalamus fulfills not only the reception of temperature shifts, i.e. the primary processing of information, but its further analysis as well."} {"id": "PMID:1254053", "title": "[Responses of directionally sensitive neurons of the frog midbrain tectum, their adaptation and extrapolation responses].", "content": "The greatest coherence of responses and latency for neuronal pairs was found at interelectrode distances up to 300 microns which is due, apparently, to dimensions of the afferent fibers' branching areas. The adaptation and extrapolation features observed in majority of the neurons, were more obvious in the tectum nuclear layers rather than in the fiber those. The more stable responses of the fiber layers' neurons suggest a representation of branches stemming from the fibers of the retina ganglionic cells, while in the nuclear layers the elements with high adaptability: the \"novelty neurons\", are localized.", "contents": "[Responses of directionally sensitive neurons of the frog midbrain tectum, their adaptation and extrapolation responses]. The greatest coherence of responses and latency for neuronal pairs was found at interelectrode distances up to 300 microns which is due, apparently, to dimensions of the afferent fibers' branching areas. The adaptation and extrapolation features observed in majority of the neurons, were more obvious in the tectum nuclear layers rather than in the fiber those. The more stable responses of the fiber layers' neurons suggest a representation of branches stemming from the fibers of the retina ganglionic cells, while in the nuclear layers the elements with high adaptability: the \"novelty neurons\", are localized."} {"id": "PMID:1254054", "title": "[Reflection of visceral signals in the impulse activity of the caudate nucleus].", "content": "Responses of spontaneously active neurons of the caudate nucleus to stimulation of the n. splanchnicus were extracellularly recorded in immobilized cats. Presence of multimodal neurons responding to stimulation of visceral, somatic and auditory sensory systems, was also determined in this structure. The data obtained suggest probable participation of the caudate nucleus' neurons in the mechanisms of interaction between visceral signals and somatic and auditory those.", "contents": "[Reflection of visceral signals in the impulse activity of the caudate nucleus]. Responses of spontaneously active neurons of the caudate nucleus to stimulation of the n. splanchnicus were extracellularly recorded in immobilized cats. Presence of multimodal neurons responding to stimulation of visceral, somatic and auditory sensory systems, was also determined in this structure. The data obtained suggest probable participation of the caudate nucleus' neurons in the mechanisms of interaction between visceral signals and somatic and auditory those."} {"id": "PMID:1254055", "title": "[An analysis of participation of central noradrenergic structures in the process of memory trace reproduction].", "content": "Variations of the noradrenaline content in noradrenergic terminals of different nuclei of the limbic system and the anterior hypothalamus were studied by the limuniscent histochemical method in the course of reproduction of a series of conditioned reflex reacitions in male Wistar rats. Both in reproduction of a conditioned passive avoiding responce and in training with inevitable conditioned reinforcement, a decrease of the noradrenaline content was found as compared with the control level. A lesser decrease was observed both in the animals that had been trained but did not reproduce the relfex reaction, and in the trained animals after repeated testing for 4 days following the training. The reproduction of the conditioned active avoiding response in shuttle box did not entail variations in the noradrenaline content.", "contents": "[An analysis of participation of central noradrenergic structures in the process of memory trace reproduction]. Variations of the noradrenaline content in noradrenergic terminals of different nuclei of the limbic system and the anterior hypothalamus were studied by the limuniscent histochemical method in the course of reproduction of a series of conditioned reflex reacitions in male Wistar rats. Both in reproduction of a conditioned passive avoiding responce and in training with inevitable conditioned reinforcement, a decrease of the noradrenaline content was found as compared with the control level. A lesser decrease was observed both in the animals that had been trained but did not reproduce the relfex reaction, and in the trained animals after repeated testing for 4 days following the training. The reproduction of the conditioned active avoiding response in shuttle box did not entail variations in the noradrenaline content."} {"id": "PMID:1254056", "title": "[Nystagmus after unilateral destruction of the superior colliculus in rabbits].", "content": "The frequency, the amplitude of optokinetic nystagmus (OKN) the reverse postoptokinetic nystagmus (RPN) were studied in rabbits before and during the first 7 days after left-side lesions of the superior colliculi. The lesions led to a more obvious decrease in the frequency and amplitude of the OKN than in those of the RPN. The retino-colliculi pathway seems to be of greater importance for the OKN formation than for the RPN mechanism.", "contents": "[Nystagmus after unilateral destruction of the superior colliculus in rabbits]. The frequency, the amplitude of optokinetic nystagmus (OKN) the reverse postoptokinetic nystagmus (RPN) were studied in rabbits before and during the first 7 days after left-side lesions of the superior colliculi. The lesions led to a more obvious decrease in the frequency and amplitude of the OKN than in those of the RPN. The retino-colliculi pathway seems to be of greater importance for the OKN formation than for the RPN mechanism."} {"id": "PMID:1254057", "title": "[Characteristics of the reactions of neurons of successive links in the auditory pathway to changes in the timing of acoustic signals].", "content": "Afferent impulsation was compared for different levels of the auditory system: the cochlear nuclei, posterior colliculi, and the auditory cortex. While moving from the cochlear nuclei over to the posterior colliculi and the auditory cortex, the number of neurons describing the temporal structure of the amplitude-modulated signal's envelope in the impulse activity pattern, becomes sharply reduced; the number of neurons selectively responding to certain phases of the envelope increases; the firing rate of neurons of the auditory pathway's higher levels decreases; the repetition rates becomes narrow due to limitation from both the high- and the low-frequency sides. Selectivity of responses to combination of such signal parameters as the frequency of the carrier and the rhythm of the amplitude modulation, increases. Specificity of the neuronal responses increases on certain combinations of such parameters of the frequency-modulated sounds as the frequency range in the signal, the direction and speed of the frequency modulation. The data obtained revealed some general tendencies of the impulsation transformation in successive levels of the auditory pathway.", "contents": "[Characteristics of the reactions of neurons of successive links in the auditory pathway to changes in the timing of acoustic signals]. Afferent impulsation was compared for different levels of the auditory system: the cochlear nuclei, posterior colliculi, and the auditory cortex. While moving from the cochlear nuclei over to the posterior colliculi and the auditory cortex, the number of neurons describing the temporal structure of the amplitude-modulated signal's envelope in the impulse activity pattern, becomes sharply reduced; the number of neurons selectively responding to certain phases of the envelope increases; the firing rate of neurons of the auditory pathway's higher levels decreases; the repetition rates becomes narrow due to limitation from both the high- and the low-frequency sides. Selectivity of responses to combination of such signal parameters as the frequency of the carrier and the rhythm of the amplitude modulation, increases. Specificity of the neuronal responses increases on certain combinations of such parameters of the frequency-modulated sounds as the frequency range in the signal, the direction and speed of the frequency modulation. The data obtained revealed some general tendencies of the impulsation transformation in successive levels of the auditory pathway."} {"id": "PMID:1254058", "title": "[The electrical reactions and lability of an isolated nerve exposed to low-energy laser radiation].", "content": "In the frog isolated n. n. ischiadici, under permanent low-intensity laser radiation (6328 A; 0.5 mVt), the physiological lability of tissue changed in a monophasic manner towards consecutive growth. After a single illumination lasting from 1 sec to 10 min, statistically significant shifts of the maximal rhythm of impulse excitation towards an increase occur with some \"latency\" at the 10-min exposure. The maximal frequency of evoked action potentials, at that, invariably remained at the attained level. After the laser action, the irradiated portion of the nerve becomes electropositive in regard to other, intact points of the nerve. The polarization shifts are weak and not directly dependent on the exposure dose of the irradiation. The laser is concluded to evoke an increase and acceleration of metabolic processes which raises the lability level, hence the increased working capacity of the tissue.", "contents": "[The electrical reactions and lability of an isolated nerve exposed to low-energy laser radiation]. In the frog isolated n. n. ischiadici, under permanent low-intensity laser radiation (6328 A; 0.5 mVt), the physiological lability of tissue changed in a monophasic manner towards consecutive growth. After a single illumination lasting from 1 sec to 10 min, statistically significant shifts of the maximal rhythm of impulse excitation towards an increase occur with some \"latency\" at the 10-min exposure. The maximal frequency of evoked action potentials, at that, invariably remained at the attained level. After the laser action, the irradiated portion of the nerve becomes electropositive in regard to other, intact points of the nerve. The polarization shifts are weak and not directly dependent on the exposure dose of the irradiation. The laser is concluded to evoke an increase and acceleration of metabolic processes which raises the lability level, hence the increased working capacity of the tissue."} {"id": "PMID:1254060", "title": "[The effect of an inhibitor of erythropoiesis on the metabolism of tissues of various organs].", "content": "The nucleus of the bone marrow cells was shown to be the source of humoral inhibitor of erythropoiesis and to inhibit the oxidative metabolism in the bone marrow. However, the nucleus intensifies aerobic oxidative metabolism in the kidneys. Therefore the nucleus of the bone marrow cells was suggested to regulate the formation of erythropoietin in the kidneys.", "contents": "[The effect of an inhibitor of erythropoiesis on the metabolism of tissues of various organs]. The nucleus of the bone marrow cells was shown to be the source of humoral inhibitor of erythropoiesis and to inhibit the oxidative metabolism in the bone marrow. However, the nucleus intensifies aerobic oxidative metabolism in the kidneys. Therefore the nucleus of the bone marrow cells was suggested to regulate the formation of erythropoietin in the kidneys."} {"id": "PMID:1254061", "title": "[Changes in the cardiac and \"sleep--wakefulness\" cycle rhythms following isoproterenol administration to white rats].", "content": "The heart-rate during sleep-wakefulness cycle did not significantly change after isoproterenol administration. However, both the duration of R--R intervals and their dispersion became sharply increased. The observed shifts were least obvious during the slow-wave sleep. The bradycardia periods during paradoxical sleep in rats are supposed to be a beneficiary background for further suppresion of the sinus automatism up to sinoauricular blockade. The data obtained suggest that the heart-rate during wakefulness can be a reliable enough evidence of its oscillations in other phases of the cycle. The revealed changes of the sleep structure involved increasing part of paradoxical stages in the total time of sleep in animals when measuring it starting from the 5th day after the sympathomimetic administration.", "contents": "[Changes in the cardiac and \"sleep--wakefulness\" cycle rhythms following isoproterenol administration to white rats]. The heart-rate during sleep-wakefulness cycle did not significantly change after isoproterenol administration. However, both the duration of R--R intervals and their dispersion became sharply increased. The observed shifts were least obvious during the slow-wave sleep. The bradycardia periods during paradoxical sleep in rats are supposed to be a beneficiary background for further suppresion of the sinus automatism up to sinoauricular blockade. The data obtained suggest that the heart-rate during wakefulness can be a reliable enough evidence of its oscillations in other phases of the cycle. The revealed changes of the sleep structure involved increasing part of paradoxical stages in the total time of sleep in animals when measuring it starting from the 5th day after the sympathomimetic administration."} {"id": "PMID:1254062", "title": "[Pressor reflexes and changes in sympathetic impulsation and the responses of intestinal and renal vessels].", "content": "In acute experiments on cats, the ganglio-blocking agent (hexonium 2 mg/kg) revealed no high-amplitude impulsation (over 15 mcV) in the branches of intestinal and kidney nerves. Simultaneously, no responses of the small intestine and kidney resistance vessels to constriction of the carotid arteries were observed. The constrictory and dilatory responses of the capacitance vessels in the same organs, after the above dose of the ganglioblocking agent, are preserved and correlated with the character of changes of the lowamplitude (equal to or lower than 15 mcV) impulsation persisting in the intestinal and kidney nerves. The post-ganglionar sympathetic fibers conducting high-amplitude discharges are suggested to be mainly responsible for the reflex responses of the resistance vessels, while the low-amplitude fibers--for responses of the capacitance vessels.", "contents": "[Pressor reflexes and changes in sympathetic impulsation and the responses of intestinal and renal vessels]. In acute experiments on cats, the ganglio-blocking agent (hexonium 2 mg/kg) revealed no high-amplitude impulsation (over 15 mcV) in the branches of intestinal and kidney nerves. Simultaneously, no responses of the small intestine and kidney resistance vessels to constriction of the carotid arteries were observed. The constrictory and dilatory responses of the capacitance vessels in the same organs, after the above dose of the ganglioblocking agent, are preserved and correlated with the character of changes of the lowamplitude (equal to or lower than 15 mcV) impulsation persisting in the intestinal and kidney nerves. The post-ganglionar sympathetic fibers conducting high-amplitude discharges are suggested to be mainly responsible for the reflex responses of the resistance vessels, while the low-amplitude fibers--for responses of the capacitance vessels."} {"id": "PMID:1254063", "title": "[The relationship between lung volume and discharges of individual groups of pulmonary stretch receptors].", "content": "In 120 lung stretch receptors of the cat, the volume threshold, impulse frequencies in the end of inspiration and in various volumes of inflation or defleation of the lung, were studied. Low-threshold (25%), high-threshold (60%), and intermediate (15%) endings were revealed. Two types of low-threshold and four types of high-threshold receptors were singled out. Nerve fibers from various types of the lung stretch receptors were found to have similar conduction velocities.", "contents": "[The relationship between lung volume and discharges of individual groups of pulmonary stretch receptors]. In 120 lung stretch receptors of the cat, the volume threshold, impulse frequencies in the end of inspiration and in various volumes of inflation or defleation of the lung, were studied. Low-threshold (25%), high-threshold (60%), and intermediate (15%) endings were revealed. Two types of low-threshold and four types of high-threshold receptors were singled out. Nerve fibers from various types of the lung stretch receptors were found to have similar conduction velocities."} {"id": "PMID:1254065", "title": "[The hydrodynamics of the superficial cortical nephrons of the rat kidney during a diuretic response].", "content": "Diuretic response to administration of mannitol, furozemide, ethaerynic acid, and euphyllinum was invariably followed by a considerable dilation of the lumen of proximal and distal tubular of the kidney surface nephrones. Simultaneously, a considerably reduced flow of the tubular fluid was always observed except after euphyllinum administration, the latter being followed by acceleration of the flow. Questions of interrelationships between the nephrone's hydrodynamic characteristics and the processes of glomerule filtration and tubular reabsorption of the fluid and electrolytes, are discussed.", "contents": "[The hydrodynamics of the superficial cortical nephrons of the rat kidney during a diuretic response]. Diuretic response to administration of mannitol, furozemide, ethaerynic acid, and euphyllinum was invariably followed by a considerable dilation of the lumen of proximal and distal tubular of the kidney surface nephrones. Simultaneously, a considerably reduced flow of the tubular fluid was always observed except after euphyllinum administration, the latter being followed by acceleration of the flow. Questions of interrelationships between the nephrone's hydrodynamic characteristics and the processes of glomerule filtration and tubular reabsorption of the fluid and electrolytes, are discussed."} {"id": "PMID:1254066", "title": "[The effect of body temperature on biochemical changes in the blood during adaptation to cold].", "content": "The changes of the body temperature, intensity of oxidative processes, glucose content in the blood, and unesterified fatty acids (UEFA) content in the serum of the homeotherm organism were studied at +5 degrees C. The initial (1--3) coolings induced mobilization of carbohydrate and fat energetic reserves, using the blood free glucose and the serum UEFA for heatproduction. This caused hypoglycemia in some of the animals. Further (4--13) coolings were characterized by considerable fluctuations of the parameters. Excessive release of UEFA from the fat stores and their enhanced oxydation coincided with a small drop of the body temperature and a decrease in glucose concentration in the blood. By the 26th-35th exposures the animals became adapted to the temperature +5 degrees C. In the adapted organism, the prevalence of UEFA oxydation coincided with the prevalence of the free glucose entering the blood. This suggests that, in the cold-adapted organism, oxydation of UEFA keeps up the body temperature while using the blood glucose is restricted. This may be of importance for a steady maintenance of glucemic homeostasis in cold.", "contents": "[The effect of body temperature on biochemical changes in the blood during adaptation to cold]. The changes of the body temperature, intensity of oxidative processes, glucose content in the blood, and unesterified fatty acids (UEFA) content in the serum of the homeotherm organism were studied at +5 degrees C. The initial (1--3) coolings induced mobilization of carbohydrate and fat energetic reserves, using the blood free glucose and the serum UEFA for heatproduction. This caused hypoglycemia in some of the animals. Further (4--13) coolings were characterized by considerable fluctuations of the parameters. Excessive release of UEFA from the fat stores and their enhanced oxydation coincided with a small drop of the body temperature and a decrease in glucose concentration in the blood. By the 26th-35th exposures the animals became adapted to the temperature +5 degrees C. In the adapted organism, the prevalence of UEFA oxydation coincided with the prevalence of the free glucose entering the blood. This suggests that, in the cold-adapted organism, oxydation of UEFA keeps up the body temperature while using the blood glucose is restricted. This may be of importance for a steady maintenance of glucemic homeostasis in cold."} {"id": "PMID:1254073", "title": "Lifetime probability of additional births by age and parity for American women, 1935-1968: a new measurement of period fertility.", "content": "A new fertility measurement, probability that a woman of specified parity and age will bear a given number of births in her remaining lifetime, is proposed in this article. The measurement is a summary index of a set of age-parity-specific birth probabilities and in a particular case it is conceptually analogous to the total fertility by birth order but free from the influence of the parity distribution. Fertility of American women for the period 1935-1968 was studied by use of such lifetime probabilities. It appears that the trend of fertility of high birth orders has been parallel with that of low orders. Initiation of the recent decline in fertility depends on parity and age of woman.", "contents": "Lifetime probability of additional births by age and parity for American women, 1935-1968: a new measurement of period fertility. A new fertility measurement, probability that a woman of specified parity and age will bear a given number of births in her remaining lifetime, is proposed in this article. The measurement is a summary index of a set of age-parity-specific birth probabilities and in a particular case it is conceptually analogous to the total fertility by birth order but free from the influence of the parity distribution. Fertility of American women for the period 1935-1968 was studied by use of such lifetime probabilities. It appears that the trend of fertility of high birth orders has been parallel with that of low orders. Initiation of the recent decline in fertility depends on parity and age of woman."} {"id": "PMID:1254075", "title": "Constructing fertility tables for Soviet populations.", "content": "Because the 1970 Soviet Union census does not provide information on the age structure of men and women separately by sex and according to their ethnic affiliation, the 1959 USSR census data serve as the basis to infer knowledge about ethnic fertility. The model takes into account (1) the total number of births in 1960, estimated from the child-woman ratio in 1959, (2) the age structure of women in 1959, and (3) the assumed pattern of age-specific birth rates structured in terms of the modal age at childbearing and the length of the fertility age span. The results show that Ukrainians among the Slav populations ranked as the lowest with 2.07 children born per woman. Their total fertility contrasts with that of Kazakhs native to Central Asia, who reportedly according to Soviet sources had 7.46 children per woman in 1958-1959, and whose estimated rate is around 8.59 children. Extreme variations appear in the estimates of fertility among nationalities of the Caucasus region, Volga Basin, and to a lesser degree in Siberia. Official Soviet calculations of crude birth rates and age-specific rates for 15 Union Republics in 1967-1968 are transcribed and compared with the estimates for nationalities in 1959-1960. The same theoretical model used to generate the Soviet rates may be adapted under different assumptions to non-Soviet populations in other situations where the data are scanty or incomplete.", "contents": "Constructing fertility tables for Soviet populations. Because the 1970 Soviet Union census does not provide information on the age structure of men and women separately by sex and according to their ethnic affiliation, the 1959 USSR census data serve as the basis to infer knowledge about ethnic fertility. The model takes into account (1) the total number of births in 1960, estimated from the child-woman ratio in 1959, (2) the age structure of women in 1959, and (3) the assumed pattern of age-specific birth rates structured in terms of the modal age at childbearing and the length of the fertility age span. The results show that Ukrainians among the Slav populations ranked as the lowest with 2.07 children born per woman. Their total fertility contrasts with that of Kazakhs native to Central Asia, who reportedly according to Soviet sources had 7.46 children per woman in 1958-1959, and whose estimated rate is around 8.59 children. Extreme variations appear in the estimates of fertility among nationalities of the Caucasus region, Volga Basin, and to a lesser degree in Siberia. Official Soviet calculations of crude birth rates and age-specific rates for 15 Union Republics in 1967-1968 are transcribed and compared with the estimates for nationalities in 1959-1960. The same theoretical model used to generate the Soviet rates may be adapted under different assumptions to non-Soviet populations in other situations where the data are scanty or incomplete."} {"id": "PMID:1254076", "title": "A modification of a continuous time model for first conception.", "content": "The interval between marriage and the first conception leading to a live birth plays an important role in the determination of fertility components. Several probability models (Potter and Parker, 1964; Singh, 1961, 1964, 1967) based on varying sets of assumptions relating to this interval have been propounded in the recent past. All of them are based on the assumption that the females under study are susceptible to conception at the time of marriage. However, in certain situations, where some of the females already pregnant at the time of marriage report to have conceived within a short interval following marriage, this condition is not satisfied and these models become unsuitable. A probability distribution which is an inflated form of the continuous model proposed by Singh, for the time of the first conception leading to a live birth, is presented in this paper. It describes reasonably well the data on first conception times in the context of premarital conceptions. Simple expressions for the maximum likelihood estimators of the parameters involved in the model are obtained and a method for finding the asymptotic covariance matrix of the estimators is outlined. The model is applied to four sets of data.", "contents": "A modification of a continuous time model for first conception. The interval between marriage and the first conception leading to a live birth plays an important role in the determination of fertility components. Several probability models (Potter and Parker, 1964; Singh, 1961, 1964, 1967) based on varying sets of assumptions relating to this interval have been propounded in the recent past. All of them are based on the assumption that the females under study are susceptible to conception at the time of marriage. However, in certain situations, where some of the females already pregnant at the time of marriage report to have conceived within a short interval following marriage, this condition is not satisfied and these models become unsuitable. A probability distribution which is an inflated form of the continuous model proposed by Singh, for the time of the first conception leading to a live birth, is presented in this paper. It describes reasonably well the data on first conception times in the context of premarital conceptions. Simple expressions for the maximum likelihood estimators of the parameters involved in the model are obtained and a method for finding the asymptotic covariance matrix of the estimators is outlined. The model is applied to four sets of data."} {"id": "PMID:1254077", "title": "Parity patterns of birth interval distribution.", "content": "A simplified model is presented for the measurement of inter-live birth interval distributions. Comparative analyses of \"effective fecundability,\" the mean length and variation of postpartum infecundity, and the parity progression ratio based on this measurement model are presented using data from U.S. marriage cohorts and from an Indian sample. Parity differentials in these reproduction parameters are investigated, and the ramifications for fertility estimate and projection discussed.", "contents": "Parity patterns of birth interval distribution. A simplified model is presented for the measurement of inter-live birth interval distributions. Comparative analyses of \"effective fecundability,\" the mean length and variation of postpartum infecundity, and the parity progression ratio based on this measurement model are presented using data from U.S. marriage cohorts and from an Indian sample. Parity differentials in these reproduction parameters are investigated, and the ramifications for fertility estimate and projection discussed."} {"id": "PMID:1254078", "title": "Immigration policies and trends: a comparison of Canada and the United States.", "content": "This paper discusses recent migration to North America with reference to the 1962 and 1967 Canadian immigration regulations and the 1965 United States Immigration and Nationality Act. Despite the similar emphasis on manpower and kinship criteria as the basis for the admission of immigrants, differences between Canada and the United States exist with respect to the importance of immigration for the respective economies, the organization of immigration, the formal regulations, and the size and composition of migrant streams. After an examination of the volume, origin, and occupational composition of immigration to Canada and the United States, flows between the two countries are studied. The paper concludes with a scrutiny of changes in immigration regulations which are pending in both countries.", "contents": "Immigration policies and trends: a comparison of Canada and the United States. This paper discusses recent migration to North America with reference to the 1962 and 1967 Canadian immigration regulations and the 1965 United States Immigration and Nationality Act. Despite the similar emphasis on manpower and kinship criteria as the basis for the admission of immigrants, differences between Canada and the United States exist with respect to the importance of immigration for the respective economies, the organization of immigration, the formal regulations, and the size and composition of migrant streams. After an examination of the volume, origin, and occupational composition of immigration to Canada and the United States, flows between the two countries are studied. The paper concludes with a scrutiny of changes in immigration regulations which are pending in both countries."} {"id": "PMID:1254079", "title": "The anatomy of the parotoid gland in Bufonidae with some histochemical findings. II. Bufo alvarius.", "content": "The gross and microscopic anatomy of the venom producing parotoid glands of Bufo alvarius has been studied by light and electron microscopy. Histochemical reactions for the presence of venom constituents and of components in biochemical pathways in the synthesis and release of venom were performed. The gland is composed of numerous lobules. Each lobule is an individual unit with a lumen surrounded by a double cell layer. Microvilli of the outer layer interdigitate with microvilli of the inner layer. Cells of the outer layer resemble smooth muscle cells, are rich in adenosine triphosphatase and glucose-6-phosphatase, and contain numerous pinocytotic vesicles, glycogen granules and various organelles. These organelles include \"crystalloids\" of what seem to be highly organized agranular reticulum. These outer layer cells probably function in some aspects of venom synthesis, active cellular transport and contraction in the discharge of the secretory product. The inner cell layer demonstrates a positive chromaffin reaction, contains steroid material, various organelles, some pinocytotic vesicles and glycogen granules, and appears devoid of a plasmalemma on its inner surface. This layer is probably involved in venom formation and release via an apocrine type of secretion. Bufo alvarius parotid gland shows significant morphological and histochemical differences from that of B. marinus and more nearly resembles a typical steroid producing organ.", "contents": "The anatomy of the parotoid gland in Bufonidae with some histochemical findings. II. Bufo alvarius. The gross and microscopic anatomy of the venom producing parotoid glands of Bufo alvarius has been studied by light and electron microscopy. Histochemical reactions for the presence of venom constituents and of components in biochemical pathways in the synthesis and release of venom were performed. The gland is composed of numerous lobules. Each lobule is an individual unit with a lumen surrounded by a double cell layer. Microvilli of the outer layer interdigitate with microvilli of the inner layer. Cells of the outer layer resemble smooth muscle cells, are rich in adenosine triphosphatase and glucose-6-phosphatase, and contain numerous pinocytotic vesicles, glycogen granules and various organelles. These organelles include \"crystalloids\" of what seem to be highly organized agranular reticulum. These outer layer cells probably function in some aspects of venom synthesis, active cellular transport and contraction in the discharge of the secretory product. The inner cell layer demonstrates a positive chromaffin reaction, contains steroid material, various organelles, some pinocytotic vesicles and glycogen granules, and appears devoid of a plasmalemma on its inner surface. This layer is probably involved in venom formation and release via an apocrine type of secretion. Bufo alvarius parotid gland shows significant morphological and histochemical differences from that of B. marinus and more nearly resembles a typical steroid producing organ."} {"id": "PMID:1254101", "title": "Duration of early visual experience and visual cliff behavior of chicks.", "content": "Visual cliff behavior was studied in 120 chicks as a function of 22, 46, 70, 94, or 118 hr of rearing in a deep or shallow environment. Preference for the deep side of the visual cliff increased directly with duration of depth-rearing but was uninfluenced at any duration of shallow-rearing. Although qualitative differences existed in the behaviors of those shallow- and deep-reared chicks which crossed the cliff, the loss of depth avoidance by the latter group appeared to be specific to the rearing and testing apparatus.", "contents": "Duration of early visual experience and visual cliff behavior of chicks. Visual cliff behavior was studied in 120 chicks as a function of 22, 46, 70, 94, or 118 hr of rearing in a deep or shallow environment. Preference for the deep side of the visual cliff increased directly with duration of depth-rearing but was uninfluenced at any duration of shallow-rearing. Although qualitative differences existed in the behaviors of those shallow- and deep-reared chicks which crossed the cliff, the loss of depth avoidance by the latter group appeared to be specific to the rearing and testing apparatus."} {"id": "PMID:1254102", "title": "Developmental patterns of seizure susceptibility in inbred strains of mice.", "content": "Samples of mice from each of 6 inbred strains were tested for audiogenic and electroconvulsive seizures at 5 ages (14, 21, 28, 35, and 42 days). A moderately large within-strain correlation (.67) was found, indicating that developmental patterns of susceptibility to audiogenic and electroconvulsive seizures are similar within each strain. The finding of an even larger between-strain correlation (.91) indicated that strains which are highly susceptible to audiogenic seizures are also likely to be highly susceptible to electroconvulsive seizures. In a 2nd experiment, whole brain norepinephrine and serotonin were assayed in each of 5 inbred strains at 21 and 42 days of age. Results were consistent with the hypothesis that levels of these amines are inversely related to seizure susceptibility. Mice from strains which were susceptible to seizures at 21 days of age had significantly lower levels of norepinephrine and serotonin in brain than did 42-day-old, seizure-resistant animals.", "contents": "Developmental patterns of seizure susceptibility in inbred strains of mice. Samples of mice from each of 6 inbred strains were tested for audiogenic and electroconvulsive seizures at 5 ages (14, 21, 28, 35, and 42 days). A moderately large within-strain correlation (.67) was found, indicating that developmental patterns of susceptibility to audiogenic and electroconvulsive seizures are similar within each strain. The finding of an even larger between-strain correlation (.91) indicated that strains which are highly susceptible to audiogenic seizures are also likely to be highly susceptible to electroconvulsive seizures. In a 2nd experiment, whole brain norepinephrine and serotonin were assayed in each of 5 inbred strains at 21 and 42 days of age. Results were consistent with the hypothesis that levels of these amines are inversely related to seizure susceptibility. Mice from strains which were susceptible to seizures at 21 days of age had significantly lower levels of norepinephrine and serotonin in brain than did 42-day-old, seizure-resistant animals."} {"id": "PMID:1254103", "title": "Absence of effects of corticosterone given at 22 days.", "content": "Mice given a single large dose of corticosterone at 2 days of age, and tested when adult, have shown lasting alterations in operant behavior, associated with reductions in cerebral weight and DNA content. When mice were given corticosterone at 22 days, no changes appeared in cerebral weight, DNA, or in operant behavior, but an apparent decrease did occur in open-field activity. The results suggest that the effects of corticosterone treatment at 2 days on the developing brain are mediated by one or more types of sensitivity to the steroid that have been largely lost by 22 days.", "contents": "Absence of effects of corticosterone given at 22 days. Mice given a single large dose of corticosterone at 2 days of age, and tested when adult, have shown lasting alterations in operant behavior, associated with reductions in cerebral weight and DNA content. When mice were given corticosterone at 22 days, no changes appeared in cerebral weight, DNA, or in operant behavior, but an apparent decrease did occur in open-field activity. The results suggest that the effects of corticosterone treatment at 2 days on the developing brain are mediated by one or more types of sensitivity to the steroid that have been largely lost by 22 days."} {"id": "PMID:1254104", "title": "Rapid changes in cerebral blood flow and initial visual experience in the developing chick.", "content": "A single eye of young chicks was sewed shut for various times. Regions contralateral to and primarily or secondarily innervated by the sutured eye had a reduced rate of cerebral blood flow in comparison to the corresponding ipsilateral regions. However, upon reopening the sutured eye after 2 days, these contralateral regions (optic lobes and cerebral hemispheres) exhibited a rapid increase in cerebral blood flow to a level significantly above that in control ipsilateral areas. The duration of this effect was considerably prolonged in chicks that were monocularly sutured immediately after hatching without prior exposure to light. Chicks that had 1 week of normal vision before monocular suture did not show this overcompensatory effect. If the period of monocular suture was extended to 7 days before restoration of vision to the occluded eye, the overcompensatory vascular effect was delayed. The maximal effect was apparent only upon the 1st exposure of an eye to major visual input. A possible relation exists between this rapid increase in regional blood flow and the period when visual imprinting could normally be expected to be maximal.", "contents": "Rapid changes in cerebral blood flow and initial visual experience in the developing chick. A single eye of young chicks was sewed shut for various times. Regions contralateral to and primarily or secondarily innervated by the sutured eye had a reduced rate of cerebral blood flow in comparison to the corresponding ipsilateral regions. However, upon reopening the sutured eye after 2 days, these contralateral regions (optic lobes and cerebral hemispheres) exhibited a rapid increase in cerebral blood flow to a level significantly above that in control ipsilateral areas. The duration of this effect was considerably prolonged in chicks that were monocularly sutured immediately after hatching without prior exposure to light. Chicks that had 1 week of normal vision before monocular suture did not show this overcompensatory effect. If the period of monocular suture was extended to 7 days before restoration of vision to the occluded eye, the overcompensatory vascular effect was delayed. The maximal effect was apparent only upon the 1st exposure of an eye to major visual input. A possible relation exists between this rapid increase in regional blood flow and the period when visual imprinting could normally be expected to be maximal."} {"id": "PMID:1254105", "title": "The influence of incubatory photic stimuli on chicks' visual intensity preference for approach behavior.", "content": "Incubating chicks were presented with a high-intensity or low-intensity photic flicker stimulus, or with no photic stimulation. The chicks were tested at 16 hr posthatching for approach behavior, or at 96 hr for imprinting performance to the 2 visual flicker stimuli. The data were analyzed in accord with the arguments of whether those stimuli that effectively elicit approach behavior are determined by interaction between maturation and experience or by a genetic program. The results show that prehatch exposure to photic flicker stimuli affects initial approach behavior and imprinting performance, supporting the interaction position in opposition to the genetically programmed position.", "contents": "The influence of incubatory photic stimuli on chicks' visual intensity preference for approach behavior. Incubating chicks were presented with a high-intensity or low-intensity photic flicker stimulus, or with no photic stimulation. The chicks were tested at 16 hr posthatching for approach behavior, or at 96 hr for imprinting performance to the 2 visual flicker stimuli. The data were analyzed in accord with the arguments of whether those stimuli that effectively elicit approach behavior are determined by interaction between maturation and experience or by a genetic program. The results show that prehatch exposure to photic flicker stimuli affects initial approach behavior and imprinting performance, supporting the interaction position in opposition to the genetically programmed position."} {"id": "PMID:1254106", "title": "The development of response to continuous auditory stimulation in rats treated neonatally with 6-hydroxydopamine.", "content": "This study investigated biochemical substrates of the continuous stimulation effect, i.e. the developmental phenomenon whereby continuous stimulation depresses arousal level. Neonatal rats were injected intracisternally with 6-hydroxydopamine. Motility, heart rate, and brain amines were measured in theses animals, as well as in injected and noninjected control animals, at 14 and 28 days of age in an own-control design with and without continuous auditory stimulation. Brain norepinephrine was significantly and inversely related to the magnitude of the continuous stimulation effect and experimental-control differences increased with age. These results indicate that an intact catecholaminergic system is necessary for the mediation of increased arousal during stimulation.", "contents": "The development of response to continuous auditory stimulation in rats treated neonatally with 6-hydroxydopamine. This study investigated biochemical substrates of the continuous stimulation effect, i.e. the developmental phenomenon whereby continuous stimulation depresses arousal level. Neonatal rats were injected intracisternally with 6-hydroxydopamine. Motility, heart rate, and brain amines were measured in theses animals, as well as in injected and noninjected control animals, at 14 and 28 days of age in an own-control design with and without continuous auditory stimulation. Brain norepinephrine was significantly and inversely related to the magnitude of the continuous stimulation effect and experimental-control differences increased with age. These results indicate that an intact catecholaminergic system is necessary for the mediation of increased arousal during stimulation."} {"id": "PMID:1254107", "title": "Audiogenic priming in DBA/2J and C57BL/6J mice: interactions among age, prime-to-test interval and index of seizure.", "content": "C57BL/6J mice, not susceptible to audiogenic seizures (AGS) on the 1st exposure to an acoustic stimulus, were exposed to the acoustic stimulus for 1 min and then tested at some later date (acoustic priming). They were first exposed at either 8, 16, 19, 22, or 28 days of age, and then tested for AGS 2-16 days after priming. DBA/2J mice, susceptible to AGS on the 1st exposure to intense noise, were exposed to the acoustic stimulus at 26 days of age, and then again 2-14 days later. Data indicate that the incidence of AGS upon the 2nd exposure to the acoustic stimulus is a function of age at priming, the prime-to-test interval in days, and the index of seizures. In the case of DBA mice, later effects are also dependent on the initial level of seizure.", "contents": "Audiogenic priming in DBA/2J and C57BL/6J mice: interactions among age, prime-to-test interval and index of seizure. C57BL/6J mice, not susceptible to audiogenic seizures (AGS) on the 1st exposure to an acoustic stimulus, were exposed to the acoustic stimulus for 1 min and then tested at some later date (acoustic priming). They were first exposed at either 8, 16, 19, 22, or 28 days of age, and then tested for AGS 2-16 days after priming. DBA/2J mice, susceptible to AGS on the 1st exposure to intense noise, were exposed to the acoustic stimulus at 26 days of age, and then again 2-14 days later. Data indicate that the incidence of AGS upon the 2nd exposure to the acoustic stimulus is a function of age at priming, the prime-to-test interval in days, and the index of seizures. In the case of DBA mice, later effects are also dependent on the initial level of seizure."} {"id": "PMID:1254108", "title": "Department of Medicina, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Brazil.", "content": "The acute and late phases of insulin secretion were studied in mongrel dogs before and after the induction of mild alloxan diabetes. Fasting glucose and insulin levels were unchanged from pretreatment values. The alloxan-diabetic dogs had significantly decreased early-phase insulin responses to glucose pulses (0.5 gm./kg.) and slower plasma glucose disappearance rates. In contrast, these mildly diabetic dogs achieved comparable insulin levels and higher glucose levels during a four-hour 40 mg./min. glucose infusion than pre-alloxan control values. Similar findings in human congenital mild diabetes have been interpreted as beta cell insensitivity or impedance to efficiency of plasma glucose uptake. The present observations in alloxan-induced mild diabetes in dogs suggest that reduced early-phase secretion and intact later phase of insulin secretion are not dependent on genetic determinants and may be induced in a model of acquired diabetes.", "contents": "Department of Medicina, Faculdade de Medicina da Universidade de S\u00e3o Paulo, Brazil. The acute and late phases of insulin secretion were studied in mongrel dogs before and after the induction of mild alloxan diabetes. Fasting glucose and insulin levels were unchanged from pretreatment values. The alloxan-diabetic dogs had significantly decreased early-phase insulin responses to glucose pulses (0.5 gm./kg.) and slower plasma glucose disappearance rates. In contrast, these mildly diabetic dogs achieved comparable insulin levels and higher glucose levels during a four-hour 40 mg./min. glucose infusion than pre-alloxan control values. Similar findings in human congenital mild diabetes have been interpreted as beta cell insensitivity or impedance to efficiency of plasma glucose uptake. The present observations in alloxan-induced mild diabetes in dogs suggest that reduced early-phase secretion and intact later phase of insulin secretion are not dependent on genetic determinants and may be induced in a model of acquired diabetes."} {"id": "PMID:1254109", "title": "Growth hormone levels in diabetes. Correlation with the clinical control of the disease.", "content": "We carried out contemporaneous daytime blood sugar and growth hormone (HGH) determinations in eight juvenile and six middle-aged diabetics under both poor and good metabolic control. A continuous blood sampling technic was used. The following results were obtained: 1. HGH values in poorly controlled diabetics were higher and more fluctuating than in normals of a corresponding age. 2. After good control was reached, a significant HGH decrease was observed in all patients but one. In this condition HGH levels were normalized in middle-aged diabetics but not in juvenile ones. In the latter group HGH values, even if decreased, were persistently higher than in controls of the same age. 3. No difference was observed between newly diagnosed diabetics and patients known to have had diabetes for some years. Our data support the suggestion that HGH abnormalities in diabetes are a consequence of the metabolic disturbance.", "contents": "Growth hormone levels in diabetes. Correlation with the clinical control of the disease. We carried out contemporaneous daytime blood sugar and growth hormone (HGH) determinations in eight juvenile and six middle-aged diabetics under both poor and good metabolic control. A continuous blood sampling technic was used. The following results were obtained: 1. HGH values in poorly controlled diabetics were higher and more fluctuating than in normals of a corresponding age. 2. After good control was reached, a significant HGH decrease was observed in all patients but one. In this condition HGH levels were normalized in middle-aged diabetics but not in juvenile ones. In the latter group HGH values, even if decreased, were persistently higher than in controls of the same age. 3. No difference was observed between newly diagnosed diabetics and patients known to have had diabetes for some years. Our data support the suggestion that HGH abnormalities in diabetes are a consequence of the metabolic disturbance."} {"id": "PMID:1254110", "title": "Tumor hypoglycemia: deficient splanchnic glucose output and deficient glucagon secretion.", "content": "Fasting hypoglycemia occurred in a patient with a histologically benign mesothelioma; the serum insulin was low (2-4 muU./ml.), as was the glucose utilization rate. Splanchnic glucose output was markedly decreased on direct measurement (21 mg./min.; normal: 108-180 mg./min.). Splanchnic uptake of gluconeogenic substrates plasma glucagon was low normal during hypoglycemia and responded poorly to oral and intravenous alanine. The nonsuppressible insulin-like (NSILA-s) and somatomedin-like activities of the serum were not elevated, and the tumor did not release insulin-like activity on incubation nor did it contain somatostatin. The marked decrease in splanchnic glucose output was the principal cause of hypoglycemia, was associated with an apparent decrease in glycogenolysis, and was at least partly due to deficient glucagon secretion. The relationship of the tumor to these defects is unclear. The tumor may have secreted an unknown insulin-like material affecting primarily the liver and/or pancreatic alpha cell. The approach used here may serve as a paradigm for the analysis of hypoglycemia not caused by excessive insulin.", "contents": "Tumor hypoglycemia: deficient splanchnic glucose output and deficient glucagon secretion. Fasting hypoglycemia occurred in a patient with a histologically benign mesothelioma; the serum insulin was low (2-4 muU./ml.), as was the glucose utilization rate. Splanchnic glucose output was markedly decreased on direct measurement (21 mg./min.; normal: 108-180 mg./min.). Splanchnic uptake of gluconeogenic substrates plasma glucagon was low normal during hypoglycemia and responded poorly to oral and intravenous alanine. The nonsuppressible insulin-like (NSILA-s) and somatomedin-like activities of the serum were not elevated, and the tumor did not release insulin-like activity on incubation nor did it contain somatostatin. The marked decrease in splanchnic glucose output was the principal cause of hypoglycemia, was associated with an apparent decrease in glycogenolysis, and was at least partly due to deficient glucagon secretion. The relationship of the tumor to these defects is unclear. The tumor may have secreted an unknown insulin-like material affecting primarily the liver and/or pancreatic alpha cell. The approach used here may serve as a paradigm for the analysis of hypoglycemia not caused by excessive insulin."} {"id": "PMID:1254111", "title": "Growth of rabbit aortic smooth-muscle cells cultured in media containing diabetic and hyperlipemic serum.", "content": "Smooth-muscle cell cultures were grown from thoracic aortas of normal and diabetic rabbits. The effect of diabetic rabbit serum on the growth of these cultures was studied both in the first, rapid-growth phase and the following, more \"stationary\" phase of growth. Control experiments were carried out on normal sera to which glucose had been added. The concentrations of cholesterol, phospholipid, and triglyceride were same in both normal and diabetic sera. Media containing diabetic serum stimulated the growth of cultures significantly in both phases (2p less than 0.01). This occurred in experiments utilizing cells from normal as well as from diabetic rabbits. Control media containing normal serum with added glucose had no such effect. The growth-promoting effects of diabetic serum and of hyperlipemic serum from nondiabetic rabbits were of the same order of magnitude. Autoradiographic studies showed that the number of 3H-thymidine-labeled cells increased significantly after culture in diabetic serum (2p less than 0.005). Cells cultured from the very beginning in diabetic serum or normal serum with added glucose were significantly larger than cells grown in control serum (2p less than 0.05 and 2p less than 0.01, respectively). Cells grown in hyperlipemic serum were significantly smaller than those grown in normal serum (2p less than 0.01). These results indicate that diabetic serum contains a factor or factors that stimulate the arterial medial cell to excessive growth. This factor is not glucose, insulin, or lipid. The results may be of relevance for the understanding of human diabetic macroangiopathy.", "contents": "Growth of rabbit aortic smooth-muscle cells cultured in media containing diabetic and hyperlipemic serum. Smooth-muscle cell cultures were grown from thoracic aortas of normal and diabetic rabbits. The effect of diabetic rabbit serum on the growth of these cultures was studied both in the first, rapid-growth phase and the following, more \"stationary\" phase of growth. Control experiments were carried out on normal sera to which glucose had been added. The concentrations of cholesterol, phospholipid, and triglyceride were same in both normal and diabetic sera. Media containing diabetic serum stimulated the growth of cultures significantly in both phases (2p less than 0.01). This occurred in experiments utilizing cells from normal as well as from diabetic rabbits. Control media containing normal serum with added glucose had no such effect. The growth-promoting effects of diabetic serum and of hyperlipemic serum from nondiabetic rabbits were of the same order of magnitude. Autoradiographic studies showed that the number of 3H-thymidine-labeled cells increased significantly after culture in diabetic serum (2p less than 0.005). Cells cultured from the very beginning in diabetic serum or normal serum with added glucose were significantly larger than cells grown in control serum (2p less than 0.05 and 2p less than 0.01, respectively). Cells grown in hyperlipemic serum were significantly smaller than those grown in normal serum (2p less than 0.01). These results indicate that diabetic serum contains a factor or factors that stimulate the arterial medial cell to excessive growth. This factor is not glucose, insulin, or lipid. The results may be of relevance for the understanding of human diabetic macroangiopathy."} {"id": "PMID:1254112", "title": "Effect of insulin on the exaggerated glucagon response to arginine stimulation in diabetes mellitus.", "content": "The effect of insulin on the glucagon response to intravenous arginine was studied in eight juvenile-type and six adult-onset diabetics. In the juvenile-type diabetics, concomitant administration of insulin significantly blunted the glucagon response from a mean maximal rise of 310 +/- 54 pg./ml. to only 184 +/- 39 pg./ml. (p less than 0.01), about the same as in nondiabetics. In the adult-onset patients, however, insulin had no effect, the mean maximal rise being 250 +/- 50 pg./ml. without insulin and 307 +/- 71 pg./ml. with insulin (N.S.). This study demonstrates that in juvenile-type diabetics concomitant administration of supraphysiologic quantities of insulin can reduce the exaggerated glucagon response to intravenous arginine to normal, whereas in the adult-type group, it has no apparent effect.", "contents": "Effect of insulin on the exaggerated glucagon response to arginine stimulation in diabetes mellitus. The effect of insulin on the glucagon response to intravenous arginine was studied in eight juvenile-type and six adult-onset diabetics. In the juvenile-type diabetics, concomitant administration of insulin significantly blunted the glucagon response from a mean maximal rise of 310 +/- 54 pg./ml. to only 184 +/- 39 pg./ml. (p less than 0.01), about the same as in nondiabetics. In the adult-onset patients, however, insulin had no effect, the mean maximal rise being 250 +/- 50 pg./ml. without insulin and 307 +/- 71 pg./ml. with insulin (N.S.). This study demonstrates that in juvenile-type diabetics concomitant administration of supraphysiologic quantities of insulin can reduce the exaggerated glucagon response to intravenous arginine to normal, whereas in the adult-type group, it has no apparent effect."} {"id": "PMID:1254113", "title": "Hemoglobin AIc as an indicator of the degree of glucose intolerance in diabetes.", "content": "Hemoglobin AIc concentration, fasting blood sugar, response to an oral glucose tolerance test, and skeletal muscle capillary basement membrane thickness were measured in diabetic patients. Hemoglobin AIc concentration correlates with both response to a glucose tolerance test (r = 0.82, p less than 0.001) and fasting blood sugar (r = 0.62, p less than 0.001). The correlation of hemoglobin AIc concentration with glucose tolerance is independent of fasting blood sugar concentration (partial r = 0.61, p less than 0.005), whereas that of hemoglobin AIc with fasting blood sugar probably reflects the relationship between fasting blood sugar levels and glucose tolerance (partial r = 0.22, p less than 0.05). Hemoglobin AIc levels do not correlate with basement membrane thickness ( r = 0.15, p less than 0.05).", "contents": "Hemoglobin AIc as an indicator of the degree of glucose intolerance in diabetes. Hemoglobin AIc concentration, fasting blood sugar, response to an oral glucose tolerance test, and skeletal muscle capillary basement membrane thickness were measured in diabetic patients. Hemoglobin AIc concentration correlates with both response to a glucose tolerance test (r = 0.82, p less than 0.001) and fasting blood sugar (r = 0.62, p less than 0.001). The correlation of hemoglobin AIc concentration with glucose tolerance is independent of fasting blood sugar concentration (partial r = 0.61, p less than 0.005), whereas that of hemoglobin AIc with fasting blood sugar probably reflects the relationship between fasting blood sugar levels and glucose tolerance (partial r = 0.22, p less than 0.05). Hemoglobin AIc levels do not correlate with basement membrane thickness ( r = 0.15, p less than 0.05)."} {"id": "PMID:1254114", "title": "The effect of oxytetracycline on the response to insulin of diaphragm muscle and on lipid synthesis in vivo and in vitro in the ob/ob mouse.", "content": "The insulin sensitivity of the peripheral tissues in ob/ob mice treated with oxytetracycline was assessed both in vivo and in vitro by measuring the effect of insulin on the incorporation of glucose into glycogen in diaphragm muscle and on the incorporation of glucose and 3H2O into lipids in epidymal adipose tissue. The results indicated that OTC treatment improved the insulin sensitivity of muscle but not that of adipose tissue. The results presented also indicated that oxytetracycline treatment led to a decrease in the basal incorporation of lipids into the liver in vivo and the adipose tissue in vivo and in vitro. The results are discussed in view of the relative importance of liver and adipose tissue in the lipid metabolism of ob/ob and lean mice and in view of results obtained by other workers on the effects of B-cell cytotoxic agents.", "contents": "The effect of oxytetracycline on the response to insulin of diaphragm muscle and on lipid synthesis in vivo and in vitro in the ob/ob mouse. The insulin sensitivity of the peripheral tissues in ob/ob mice treated with oxytetracycline was assessed both in vivo and in vitro by measuring the effect of insulin on the incorporation of glucose into glycogen in diaphragm muscle and on the incorporation of glucose and 3H2O into lipids in epidymal adipose tissue. The results indicated that OTC treatment improved the insulin sensitivity of muscle but not that of adipose tissue. The results presented also indicated that oxytetracycline treatment led to a decrease in the basal incorporation of lipids into the liver in vivo and the adipose tissue in vivo and in vitro. The results are discussed in view of the relative importance of liver and adipose tissue in the lipid metabolism of ob/ob and lean mice and in view of results obtained by other workers on the effects of B-cell cytotoxic agents."} {"id": "PMID:1254115", "title": "Diabetes, prediabetes and uricaemia.", "content": "Three diabetes surveys carried out at two yearly intervals on 10000 men aged 40 years and over have enabled us to compare four groups of subjects with regard to their serum uric acid level in relation to carbohydrate metabolism. Prediabetics, that is, persons who screened negative at previous surveys and subsequently developed diabetes, had a higher mean uric acid level than normals (p less than 0.001). Their uric acid level was considerably higher than in diabetics, who had a mean value lower than normals (up to p less than 0.001). Men, without diabetes, but having an abnormal GTT were found to have a mean value higher than the normals at each survey.", "contents": "Diabetes, prediabetes and uricaemia. Three diabetes surveys carried out at two yearly intervals on 10000 men aged 40 years and over have enabled us to compare four groups of subjects with regard to their serum uric acid level in relation to carbohydrate metabolism. Prediabetics, that is, persons who screened negative at previous surveys and subsequently developed diabetes, had a higher mean uric acid level than normals (p less than 0.001). Their uric acid level was considerably higher than in diabetics, who had a mean value lower than normals (up to p less than 0.001). Men, without diabetes, but having an abnormal GTT were found to have a mean value higher than the normals at each survey."} {"id": "PMID:1254116", "title": "Effects of metformin on insulin resistance after injury in the rat.", "content": "Hyperglycaemia and insulin resistance occur after injury. The effects of the antidiabetic biguanide metformin in injured rats have been studied in order to elucidate the cause of these effects. Metformin (120 mg/kg S. C.) produced a significant hypoglycaemic effect after a 20% dorsal scald but did not affect the blood glucose concentration in non-injured rats. The hypoglycaemic effect did not result from increased insulin secretion. It was associated with a reduction in liver glycogen and an increase in blood lactate concentrations, suggesting that the drug acted by promoting peripheral glucose utilization. This was confirmed by measuring the clearance rate coefficient of [5-3H]glucose. This rate coefficient was significantly increased by metformin treatment (140 mg/kg S. C.) in scalded rats, although it was not affected in non-injured rats. Intravenous glucose tolerance in scalded rats was not improved, probably because of the increased lactate concentration. Metformin (120-160 mg/kg) also produced a hypoglycaemic effect in rats after a 4 hrs period of bilateral hind-limb ischaemia, suggesting that similar metabolic changes occur after these two types of injury.", "contents": "Effects of metformin on insulin resistance after injury in the rat. Hyperglycaemia and insulin resistance occur after injury. The effects of the antidiabetic biguanide metformin in injured rats have been studied in order to elucidate the cause of these effects. Metformin (120 mg/kg S. C.) produced a significant hypoglycaemic effect after a 20% dorsal scald but did not affect the blood glucose concentration in non-injured rats. The hypoglycaemic effect did not result from increased insulin secretion. It was associated with a reduction in liver glycogen and an increase in blood lactate concentrations, suggesting that the drug acted by promoting peripheral glucose utilization. This was confirmed by measuring the clearance rate coefficient of [5-3H]glucose. This rate coefficient was significantly increased by metformin treatment (140 mg/kg S. C.) in scalded rats, although it was not affected in non-injured rats. Intravenous glucose tolerance in scalded rats was not improved, probably because of the increased lactate concentration. Metformin (120-160 mg/kg) also produced a hypoglycaemic effect in rats after a 4 hrs period of bilateral hind-limb ischaemia, suggesting that similar metabolic changes occur after these two types of injury."} {"id": "PMID:1254117", "title": "[A study of atrio-ventricular conduction in subjects with the Lown-Ganong-Levine syndrome (author's transl)].", "content": "Eight subjects with the Lown-Ganong-Levine syndrome were studied by means of His bundle recordings during sinus rhythm and during atrial pacing. During sinus rhythm in all cases, the A-H interval was lesser than the mean value observed in 10 control subjects. Atrial pacing at rates up to 190/min produced three types of responses. Four patients showed an initial increment in A-H interval, followed by a plateau response at higher rates. One patient showed an initial increment and a plateau response in A-H interval at low and intermediate rates, followed by a sudden and conspicuous increment at higher rates, indicating conduction of impulse through the A-V node, due to refractoriness of the by-pass tract. Three patients showed a progressive increase in A-H interval similar to that of normal subjects but to a lesser degree. The possible mechanisms for the different types of response are discussed.", "contents": "[A study of atrio-ventricular conduction in subjects with the Lown-Ganong-Levine syndrome (author's transl)]. Eight subjects with the Lown-Ganong-Levine syndrome were studied by means of His bundle recordings during sinus rhythm and during atrial pacing. During sinus rhythm in all cases, the A-H interval was lesser than the mean value observed in 10 control subjects. Atrial pacing at rates up to 190/min produced three types of responses. Four patients showed an initial increment in A-H interval, followed by a plateau response at higher rates. One patient showed an initial increment and a plateau response in A-H interval at low and intermediate rates, followed by a sudden and conspicuous increment at higher rates, indicating conduction of impulse through the A-V node, due to refractoriness of the by-pass tract. Three patients showed a progressive increase in A-H interval similar to that of normal subjects but to a lesser degree. The possible mechanisms for the different types of response are discussed."} {"id": "PMID:1254118", "title": "[Familial sick sinus syndrome. Observations on three cases studied (author's transl)].", "content": "Three siblings with sick sinus syndrome (SSS) are described. In each case, electrocardiogram, Hisian electrogram and sinus node recovery time were recorded, both in basic conditions and under the effect of drugs. In two cases a permanent pacemaker uas applied. The clinical and instrumental investigations were extended to 24 out of 33 cases included in the complete genealogical tree; three cases with arrhythmias were identified (atrial and ventricular extrasystoles and atrial fibrillation). From a genetic point of view, the SSS seemed to segregate a dominant autosomic character with a lower frequency of the disease in the descendants then expected, which is probably due to their low age.", "contents": "[Familial sick sinus syndrome. Observations on three cases studied (author's transl)]. Three siblings with sick sinus syndrome (SSS) are described. In each case, electrocardiogram, Hisian electrogram and sinus node recovery time were recorded, both in basic conditions and under the effect of drugs. In two cases a permanent pacemaker uas applied. The clinical and instrumental investigations were extended to 24 out of 33 cases included in the complete genealogical tree; three cases with arrhythmias were identified (atrial and ventricular extrasystoles and atrial fibrillation). From a genetic point of view, the SSS seemed to segregate a dominant autosomic character with a lower frequency of the disease in the descendants then expected, which is probably due to their low age."} {"id": "PMID:1254120", "title": "[A rare case of endocardial fibroelastosis in the left atrium simulating mitral stenosis (author's transl)].", "content": "A rare case of primary endocardial fibroelastosis, involving only the left atrium, simulating mitral stenosis is reported; the clinical and hemodynamic features which led to the diagnosis of mitral stenosis are described. The authors discuss the data upon which a differential diagnosis between the two similar diseases can be established. The suggest that isolated fibroelastosis of the left atrium could have been developed slowly because of ipoxia of the left atrium for agenesia of the circumflex coronary artery. An operation of endotelial decortication of the left atrium is described.", "contents": "[A rare case of endocardial fibroelastosis in the left atrium simulating mitral stenosis (author's transl)]. A rare case of primary endocardial fibroelastosis, involving only the left atrium, simulating mitral stenosis is reported; the clinical and hemodynamic features which led to the diagnosis of mitral stenosis are described. The authors discuss the data upon which a differential diagnosis between the two similar diseases can be established. The suggest that isolated fibroelastosis of the left atrium could have been developed slowly because of ipoxia of the left atrium for agenesia of the circumflex coronary artery. An operation of endotelial decortication of the left atrium is described."} {"id": "PMID:1254121", "title": "[Fibroplastic parietal endocarditis with L\u00f6ffler's hematic oesinophilia (author's transl)].", "content": "The clinical data and autopsy findings in a case of L\u00f6ffler endocarditis are reported. The differential diagnosis with endocardial fibrosis of East Africa is discussed. On the basis of their histological findings and recent literature the authors suggest that endocardial fibrosis follows the organization of successive fibrin layers.", "contents": "[Fibroplastic parietal endocarditis with L\u00f6ffler's hematic oesinophilia (author's transl)]. The clinical data and autopsy findings in a case of L\u00f6ffler endocarditis are reported. The differential diagnosis with endocardial fibrosis of East Africa is discussed. On the basis of their histological findings and recent literature the authors suggest that endocardial fibrosis follows the organization of successive fibrin layers."} {"id": "PMID:1254122", "title": "[Hemochromatosic cardiomyopathy. Report of a case with registration of his bundle potentials and hemodynamic examination (author's transl)].", "content": "A case of idiopathic haemochromatosis in a young adult aged 23, with pre-eminent cardiac symptoms is described. The cardiac symptoms consisted of heart failure and various types of arrhythmias (atrial and ventricular tachycardia, AV block). The haemodynamic studies revealed a biventricular diastolic hypertension; the cineangiocardiography showed a diffuse hypokinesis of the left ventricle and mitral regurgitation.", "contents": "[Hemochromatosic cardiomyopathy. Report of a case with registration of his bundle potentials and hemodynamic examination (author's transl)]. A case of idiopathic haemochromatosis in a young adult aged 23, with pre-eminent cardiac symptoms is described. The cardiac symptoms consisted of heart failure and various types of arrhythmias (atrial and ventricular tachycardia, AV block). The haemodynamic studies revealed a biventricular diastolic hypertension; the cineangiocardiography showed a diffuse hypokinesis of the left ventricle and mitral regurgitation."} {"id": "PMID:1254123", "title": "[Serial analysis of \"P-terminal force-V1\" (PTF-V1) in acute myocardial infarction (author's transl)].", "content": "P-terminal force on horizontal plane (PTF-V1) has been studied following clinical and statistical criteria in 122 subjects with acute myocardial infarction (A.M.I.) and in a control comparable group. Also the other parameters of the P-wave have been analysed. PTF-V1 is a more reliable sign than the last and has shown some modifications in connection with the clinical changes in A.M.I. The more pathologic values have been found in anterior myocardial infarction and in infarction with pump failure. There has not been possible to find so strict relation between pathologic PTF-V1 and mortality.", "contents": "[Serial analysis of \"P-terminal force-V1\" (PTF-V1) in acute myocardial infarction (author's transl)]. P-terminal force on horizontal plane (PTF-V1) has been studied following clinical and statistical criteria in 122 subjects with acute myocardial infarction (A.M.I.) and in a control comparable group. Also the other parameters of the P-wave have been analysed. PTF-V1 is a more reliable sign than the last and has shown some modifications in connection with the clinical changes in A.M.I. The more pathologic values have been found in anterior myocardial infarction and in infarction with pump failure. There has not been possible to find so strict relation between pathologic PTF-V1 and mortality."} {"id": "PMID:1254125", "title": "[Coronary spasm and acute coronary insufficiency (author's transly)].", "content": "A series of cases illustrating a spectrum of acute coronary episodes associated with transient subepicardial injury, namely the variant form of angina, angina intermedia with electrocardiographic changes similar to those of the variant angina, acute myocardial infarction complicated by variant angina with electrocardiographic changes localized to the infarcted area, acute myocardial infarction preceded and followed by variant angina, is presented. The role of a coronary spasm as a common mechanism of the above mentioned episodes is postulated. Coronarographic demonstration of this mechanism is produced.", "contents": "[Coronary spasm and acute coronary insufficiency (author's transly)]. A series of cases illustrating a spectrum of acute coronary episodes associated with transient subepicardial injury, namely the variant form of angina, angina intermedia with electrocardiographic changes similar to those of the variant angina, acute myocardial infarction complicated by variant angina with electrocardiographic changes localized to the infarcted area, acute myocardial infarction preceded and followed by variant angina, is presented. The role of a coronary spasm as a common mechanism of the above mentioned episodes is postulated. Coronarographic demonstration of this mechanism is produced."} {"id": "PMID:1254126", "title": "[A new mitral valve prosthesis (Cooley-Cutter). Experiences on 241 cases of valvular replacement (author's transl)].", "content": "A new mitral valve prosthesis (Cooley-Cutter) is described, which incorporated a low profile design, an excentric sewing cuff, a full flow orifice, a controlled regurgitation for self-washing and symmetrical peripheral flow. The new prosthesis has a titanium double-caged frame, a Pyrolite carbon poppet and a Teflon knit sewing cuff. We have attempted to incorporate in the design of this new prosthesis tre most favorable features of each of many types of prosthesis used at the Texas Heart Institute since 1962. Isolated prosthetic mitral valve replacement for severe congenital or acquired valvular disease was performed in 541 patients from June 1971 to ne 1975. Of these, 66 patients received a concomitant aortocoronary bypass and 31 tricuspid annuloplasty. In 72 patients a malfunctioning mitral prosthesis of other types was replaced with the new Cooley-Cutter prosthesis. There were 49 early deaths (9.1%) and 33 late deaths (6.1%). The most gratifying results were a low incidence of late thrombo-embolic phenomena (1.8%) and absence of hemolisis, malfunction, infection and material failure of the prosthesis.", "contents": "[A new mitral valve prosthesis (Cooley-Cutter). Experiences on 241 cases of valvular replacement (author's transl)]. A new mitral valve prosthesis (Cooley-Cutter) is described, which incorporated a low profile design, an excentric sewing cuff, a full flow orifice, a controlled regurgitation for self-washing and symmetrical peripheral flow. The new prosthesis has a titanium double-caged frame, a Pyrolite carbon poppet and a Teflon knit sewing cuff. We have attempted to incorporate in the design of this new prosthesis tre most favorable features of each of many types of prosthesis used at the Texas Heart Institute since 1962. Isolated prosthetic mitral valve replacement for severe congenital or acquired valvular disease was performed in 541 patients from June 1971 to ne 1975. Of these, 66 patients received a concomitant aortocoronary bypass and 31 tricuspid annuloplasty. In 72 patients a malfunctioning mitral prosthesis of other types was replaced with the new Cooley-Cutter prosthesis. There were 49 early deaths (9.1%) and 33 late deaths (6.1%). The most gratifying results were a low incidence of late thrombo-embolic phenomena (1.8%) and absence of hemolisis, malfunction, infection and material failure of the prosthesis."} {"id": "PMID:1254127", "title": "[Morphological aspects and electrophysiological evaluation of the vectorcardiogram in inferior myocardial infarction (author's transl)].", "content": "The purpose of the paper is to evaluate the vectorcardiographic characteristics of the QRS in inferior myocardial infarction, now extended and modified in the light of recent advances in electrophysiology. The VCGs (Frank system) of 70 patients with old inferior myocardial infarction were analyzed. The most important parameters previously considered by others and the behaviour of the different vectorial groups were considered. The results of the analysis of these parameters were concordant with those obtained by others. The morphologic evaluation of the QRS on different planes allowed our cases to be divided into five vectorcardiographic groups. The evaluation of the morphological aspects of the QRS for a more sure diagnosis of myocardial infarction, specially considering false positive cases, was considered from the semeiological point of view. Moreover, it was shown that some alterations of VCG cannot be apparent electrocardiographically. The electrogenetic meaning of vectorcardiographic alterations, probably related with depth and width of necrosis and with conduction disturbances in the subdivisions of left bundle branch, were evaluated.", "contents": "[Morphological aspects and electrophysiological evaluation of the vectorcardiogram in inferior myocardial infarction (author's transl)]. The purpose of the paper is to evaluate the vectorcardiographic characteristics of the QRS in inferior myocardial infarction, now extended and modified in the light of recent advances in electrophysiology. The VCGs (Frank system) of 70 patients with old inferior myocardial infarction were analyzed. The most important parameters previously considered by others and the behaviour of the different vectorial groups were considered. The results of the analysis of these parameters were concordant with those obtained by others. The morphologic evaluation of the QRS on different planes allowed our cases to be divided into five vectorcardiographic groups. The evaluation of the morphological aspects of the QRS for a more sure diagnosis of myocardial infarction, specially considering false positive cases, was considered from the semeiological point of view. Moreover, it was shown that some alterations of VCG cannot be apparent electrocardiographically. The electrogenetic meaning of vectorcardiographic alterations, probably related with depth and width of necrosis and with conduction disturbances in the subdivisions of left bundle branch, were evaluated."} {"id": "PMID:1254128", "title": "[Quantitative evaluation of the systolic displacement of the left ventricle profile. A cineventriculographic study (author's transl)].", "content": "A new method for evaluating the systolic displacement of the left ventricle profile is proposed. It rests on the definition of an intracardiac axis and the identification of equivalent points on cardiac end-systolic and end-diastolic silhouettes separately. Displacement in then evaluated by means of vector methods. The results in ten normal subjects are reported. Systolic displacement is visualized by means of maps, uhich reflect the geometric properties of left ventricle normal contraction.", "contents": "[Quantitative evaluation of the systolic displacement of the left ventricle profile. A cineventriculographic study (author's transl)]. A new method for evaluating the systolic displacement of the left ventricle profile is proposed. It rests on the definition of an intracardiac axis and the identification of equivalent points on cardiac end-systolic and end-diastolic silhouettes separately. Displacement in then evaluated by means of vector methods. The results in ten normal subjects are reported. Systolic displacement is visualized by means of maps, uhich reflect the geometric properties of left ventricle normal contraction."} {"id": "PMID:1254129", "title": "[Cardioangiographic evaluation of the left ventricular volume: an analysis of the various formulas used (author's transl)].", "content": "In recent years, mono and biplane cardioangiography has been used to calculate the left ventricular volume. In order to evaluate the reliability of the various methods currently most used, a study of 14 hearts removed during autopsy was carried out. The left ventricle was filled with a mixture of paraffin and Lipiodol, the hearts were then X-rayed in anteroposterior projection (AP), laterolateral (LL) and left oblique posterior (OPS) at 30 degrees. The ventricles were opened and the real volume of the cost was obtained by means of the measurement of the volume of displaced liquid. The left ventricular volume was calculated using the methods of Dodge and coll., Sandler and Dodge, Greene and coll. and Kennedy and coll. The data obtained were statistically worked out. With all the tecniques used, there was a good correlation between values of true volume and the volume calculated with the angiographic methods. The coefficient of correlation varied between 0,940 (Dodge and coll. method) and 0,979 (Sandler and Dodge method). A more detailed analysis however, demonstrated that in the hearts with lower volumes, the correlation coefficient is lower and completely unsatisfactory with the methods of Kennedy and coll. and the method of Greene and coll. In these cases some indexes of ventricualr function (stroke volume, ejection fraction) may be not reliable.", "contents": "[Cardioangiographic evaluation of the left ventricular volume: an analysis of the various formulas used (author's transl)]. In recent years, mono and biplane cardioangiography has been used to calculate the left ventricular volume. In order to evaluate the reliability of the various methods currently most used, a study of 14 hearts removed during autopsy was carried out. The left ventricle was filled with a mixture of paraffin and Lipiodol, the hearts were then X-rayed in anteroposterior projection (AP), laterolateral (LL) and left oblique posterior (OPS) at 30 degrees. The ventricles were opened and the real volume of the cost was obtained by means of the measurement of the volume of displaced liquid. The left ventricular volume was calculated using the methods of Dodge and coll., Sandler and Dodge, Greene and coll. and Kennedy and coll. The data obtained were statistically worked out. With all the tecniques used, there was a good correlation between values of true volume and the volume calculated with the angiographic methods. The coefficient of correlation varied between 0,940 (Dodge and coll. method) and 0,979 (Sandler and Dodge method). A more detailed analysis however, demonstrated that in the hearts with lower volumes, the correlation coefficient is lower and completely unsatisfactory with the methods of Kennedy and coll. and the method of Greene and coll. In these cases some indexes of ventricualr function (stroke volume, ejection fraction) may be not reliable."} {"id": "PMID:1254130", "title": "[Permanent endocardiac electric stimulation. Observations on 1125 patients (1 January 1966-31 August 1974)].", "content": "The authors report on nine years' experience with permanent endocardial pacing in the treatment of various conduction disturbances. Their experiences relate to 1125 patients; 2208 pacers were used. The age of the patients ranges from 60 to 80 (85%), 15% referring to the left decades, minimum 17 - maximum 94. Fixed rate pacers were used in 41% of cases, QRS synchronous or QRS inhibited pacers were used in 59%. Average life of pacers varies from 8.5 to 28.3 months; the average life of fixed rate pacers is higher. Complications and causes of failures, among which electrode dislodgement is the most relevant and frequent, as well as the relative therapeutical treatments, are described. Early mortality is about 1% and late mortality 8-9%: the survival rate calculated altogether after 9 years' treatment with implantable pervenous pacing is about 24%.", "contents": "[Permanent endocardiac electric stimulation. Observations on 1125 patients (1 January 1966-31 August 1974)]. The authors report on nine years' experience with permanent endocardial pacing in the treatment of various conduction disturbances. Their experiences relate to 1125 patients; 2208 pacers were used. The age of the patients ranges from 60 to 80 (85%), 15% referring to the left decades, minimum 17 - maximum 94. Fixed rate pacers were used in 41% of cases, QRS synchronous or QRS inhibited pacers were used in 59%. Average life of pacers varies from 8.5 to 28.3 months; the average life of fixed rate pacers is higher. Complications and causes of failures, among which electrode dislodgement is the most relevant and frequent, as well as the relative therapeutical treatments, are described. Early mortality is about 1% and late mortality 8-9%: the survival rate calculated altogether after 9 years' treatment with implantable pervenous pacing is about 24%."} {"id": "PMID:1254131", "title": "[The battery-state control. A new possibility for the control of pacemakers. Preliminary report (author's transl)].", "content": "After a brief examination of the technical problems of current pacemakers, with special reference to the battery state control, the authors present a new technique for such control. A power stabilizer able to generate a standard pulse of 4.3 in every condition of battery charge has been fitted on the power supply of a fixed rate pacemaker of normal production. By activating (through an external magnet) such apparatus, it is possible with an easy oscilloscopic measurement to obtain the real value of the battery voltage. Thus the comparison with previously taken measurements and the errors connected with the repetition of such measurements can be avoided. The stimulation rate and the pulse duration corresponding to the discharged state of the batteries can also be known in advance. The data obtained from the first two controls are reported.", "contents": "[The battery-state control. A new possibility for the control of pacemakers. Preliminary report (author's transl)]. After a brief examination of the technical problems of current pacemakers, with special reference to the battery state control, the authors present a new technique for such control. A power stabilizer able to generate a standard pulse of 4.3 in every condition of battery charge has been fitted on the power supply of a fixed rate pacemaker of normal production. By activating (through an external magnet) such apparatus, it is possible with an easy oscilloscopic measurement to obtain the real value of the battery voltage. Thus the comparison with previously taken measurements and the errors connected with the repetition of such measurements can be avoided. The stimulation rate and the pulse duration corresponding to the discharged state of the batteries can also be known in advance. The data obtained from the first two controls are reported."} {"id": "PMID:1254132", "title": "[The reliability of several polycardiographic indices in the quantitative evaluation of mitral stenosis (author's transl)].", "content": "In 21 patients with pure, isolated mitral stenosis, four hemodynamic parameters were studied. They were obtained by left and right cardiac catheterization and were: the mean pulmonary artery wedge pressure, the diastolic mitral gradient, the stroke volume and the mitral valve area with one or more parametres amd polycardiographic indices, to verify the reliability of the quantitative evaluation of mitral stenosis by noninvasive methods. The polycardiographic indices of Yigitbasi (r = 0.76) and Wells (r = 0.65) were best correlated with the mean pulmonary wedge pressure. The only index with a moderate correlation (r = 0.60) with the mitral diastolic gradient was that of Wells. The LVET/PEP index has only a mediocre correlation with the stroke volume (r = 0.50). The Oreshkov index was the only one among those studies to correlate at all significantly with the mitral valve area (r = --0.62). The investigation confirms the practical use of noninvasive methods in predicting the pulmonary wedge pressure, whilst the indices of Wells and Oreshkov seem less satisfactory in prediction both for the mitral diastolic gradient and the mitral valve area.", "contents": "[The reliability of several polycardiographic indices in the quantitative evaluation of mitral stenosis (author's transl)]. In 21 patients with pure, isolated mitral stenosis, four hemodynamic parameters were studied. They were obtained by left and right cardiac catheterization and were: the mean pulmonary artery wedge pressure, the diastolic mitral gradient, the stroke volume and the mitral valve area with one or more parametres amd polycardiographic indices, to verify the reliability of the quantitative evaluation of mitral stenosis by noninvasive methods. The polycardiographic indices of Yigitbasi (r = 0.76) and Wells (r = 0.65) were best correlated with the mean pulmonary wedge pressure. The only index with a moderate correlation (r = 0.60) with the mitral diastolic gradient was that of Wells. The LVET/PEP index has only a mediocre correlation with the stroke volume (r = 0.50). The Oreshkov index was the only one among those studies to correlate at all significantly with the mitral valve area (r = --0.62). The investigation confirms the practical use of noninvasive methods in predicting the pulmonary wedge pressure, whilst the indices of Wells and Oreshkov seem less satisfactory in prediction both for the mitral diastolic gradient and the mitral valve area."} {"id": "PMID:1254133", "title": "Manometric studies of the human pylorus.", "content": "The human gastroduodenal junction was investigated by means of simultaneous measurements of pressure and potential difference between skin and mucosa. An accurate and circumferentially sensitive miniature transducer assembly failed to reveal a zone of elevated pressure at the gastroduodenal junction of 8 fasting, healthy, young subjects. Additional studies were carried out with a six-lumen perfused catheter system, in which three of the pressure-transmitting catheters had openings arranged circumferentially at the same axial level. Measurements of pressure and potential difference were obtained basally during intraduodenal infusion of hydrochloric acid and after intraduodenal instillation of olive oil. In only 1 of 10 subjects was a tonic elevation in pressure recorded simultaneously by all three leads at the gastroduodenal junction. The normal human pylorus, therefore, is not reliably demonstrable as a high pressure zone.", "contents": "Manometric studies of the human pylorus. The human gastroduodenal junction was investigated by means of simultaneous measurements of pressure and potential difference between skin and mucosa. An accurate and circumferentially sensitive miniature transducer assembly failed to reveal a zone of elevated pressure at the gastroduodenal junction of 8 fasting, healthy, young subjects. Additional studies were carried out with a six-lumen perfused catheter system, in which three of the pressure-transmitting catheters had openings arranged circumferentially at the same axial level. Measurements of pressure and potential difference were obtained basally during intraduodenal infusion of hydrochloric acid and after intraduodenal instillation of olive oil. In only 1 of 10 subjects was a tonic elevation in pressure recorded simultaneously by all three leads at the gastroduodenal junction. The normal human pylorus, therefore, is not reliably demonstrable as a high pressure zone."} {"id": "PMID:1254134", "title": "Manometric studies on the human pyloric sphincter. Effect of cigarette smoking, metoclopramide, and atropine.", "content": "Pyloric sphincter pressure was assessed with water-perfused polyvinyl tubes. Smoking one cigarette significantly decreased the basal pyloric pressure, whereas 10 mg of metoclopramide as an intravenous bolus increased the pyloric pressure in normal subjects and in patients with gastric ulcer with low basal pressure. Duodenal acidification with 0.1 N HCl significantly increased pyloric pressure. Atropine 15 mug per kg, subcutaneously prevented the rise of pyloric pressure in response to acid infusion into the duodenum.", "contents": "Manometric studies on the human pyloric sphincter. Effect of cigarette smoking, metoclopramide, and atropine. Pyloric sphincter pressure was assessed with water-perfused polyvinyl tubes. Smoking one cigarette significantly decreased the basal pyloric pressure, whereas 10 mg of metoclopramide as an intravenous bolus increased the pyloric pressure in normal subjects and in patients with gastric ulcer with low basal pressure. Duodenal acidification with 0.1 N HCl significantly increased pyloric pressure. Atropine 15 mug per kg, subcutaneously prevented the rise of pyloric pressure in response to acid infusion into the duodenum."} {"id": "PMID:1254135", "title": "The effect of 16,16-dimethyl prostaglandin E2 on meal-stimulated gastric acid secretion and serum gastrin in duodenal ulcer patients.", "content": "The effect of intragastric and intraduodenal 16,16-dimethyl prostaglandin E2 (dm PGE2) on meal-stimulated gastric acid secretion and gastrin release was studied in patients with inactive duodenal ulcer. Compared to placebo, doses of 0.75, 1.00, 1.33, and 1.77 mug per kg of dm PGE2 instilled into the stomach inhibited meal-stimulated gastric acid secretion by 61 to 94% (P less than 0.01). The 1.00, 1.33, and 1.77 mug per kg doses inhibited acid secretion significantly (P less than 0.05) more than an optimal dose of propantheline bromide. Intragastric dm PGE2 (1 mug per kg) was significantly (P less than 0.05) more effective than intraduodenal dm PGE2 (1 mug per kg) in inhibiting both gastric acid secretion and gastrin release. After 1.33 and 1.77 mug per kg, some patients experienced abdominal cramps, or diarrhea, or both, but at doses of 1.00 mug per kg or less no apparent untoward side effects were observed. It is concluded that 16,16-dm PGE2 significantly inhibits meal-stimulated gastric acid secretion and gastrin release, and may be of therapeutic value in patients with peptic ulcer provided it is free of untoward side-effects with chronic administration.", "contents": "The effect of 16,16-dimethyl prostaglandin E2 on meal-stimulated gastric acid secretion and serum gastrin in duodenal ulcer patients. The effect of intragastric and intraduodenal 16,16-dimethyl prostaglandin E2 (dm PGE2) on meal-stimulated gastric acid secretion and gastrin release was studied in patients with inactive duodenal ulcer. Compared to placebo, doses of 0.75, 1.00, 1.33, and 1.77 mug per kg of dm PGE2 instilled into the stomach inhibited meal-stimulated gastric acid secretion by 61 to 94% (P less than 0.01). The 1.00, 1.33, and 1.77 mug per kg doses inhibited acid secretion significantly (P less than 0.05) more than an optimal dose of propantheline bromide. Intragastric dm PGE2 (1 mug per kg) was significantly (P less than 0.05) more effective than intraduodenal dm PGE2 (1 mug per kg) in inhibiting both gastric acid secretion and gastrin release. After 1.33 and 1.77 mug per kg, some patients experienced abdominal cramps, or diarrhea, or both, but at doses of 1.00 mug per kg or less no apparent untoward side effects were observed. It is concluded that 16,16-dm PGE2 significantly inhibits meal-stimulated gastric acid secretion and gastrin release, and may be of therapeutic value in patients with peptic ulcer provided it is free of untoward side-effects with chronic administration."} {"id": "PMID:1254136", "title": "CEA levels in fluids bathing gastrointestinal tumors.", "content": "A controlled prospective study was undertaken to determine if fluids which bathe malignancies may contain carcinoembryonic antigen (CEA) earlier in the course of gastrointestinal cancer than does plasma of the same patient and may offer a better means for diagnosis. CEA titers were normal (less than 2.5 ng per ml) in the plasma of 42 healthy volunteers. Normal CEA levels were also found in the plasma and in the colonic mucus of 14, the gastric juice of 18, duodenal drainage of 10, and bile of 11 normal control subjects. The colonic mucus of 3 patients with ulcerative colitis, gastric secretions of 5 benign gastric ulcer patients, bile specimens from 11 normal control subjects and from 5 gallstone patients contained CEA at concentrations below 2.5 ng per ml. Positive CEA titers were found in the fluids bathing tumors of all 23 patients with colonic carcinoma, 9 of 17 patients with gastric carcinoma, and all 6 patients with pancreatic carcinoma. In contrast, positive CEA titers were found in the plasma of only 16 of 23 patients with colon carcinoma, 6 of 17 patients with gastric carcinoma, and 4 of 6 patients with pancreatic carcinoma. Among 46 patients with gastrointestinal malignancies, CEA was detected in significant concentrations in the plasma of 26 patients and in fluids bathing tumors of 38 patients. These results indicate a significant association of adenocarcinoma of the colon with CEA-positive colonic mucus (P less than 0.01) and suggest the usefulness of assaying CEA in fluids bathing tumors for the detection of gastrointestinal malignancies.", "contents": "CEA levels in fluids bathing gastrointestinal tumors. A controlled prospective study was undertaken to determine if fluids which bathe malignancies may contain carcinoembryonic antigen (CEA) earlier in the course of gastrointestinal cancer than does plasma of the same patient and may offer a better means for diagnosis. CEA titers were normal (less than 2.5 ng per ml) in the plasma of 42 healthy volunteers. Normal CEA levels were also found in the plasma and in the colonic mucus of 14, the gastric juice of 18, duodenal drainage of 10, and bile of 11 normal control subjects. The colonic mucus of 3 patients with ulcerative colitis, gastric secretions of 5 benign gastric ulcer patients, bile specimens from 11 normal control subjects and from 5 gallstone patients contained CEA at concentrations below 2.5 ng per ml. Positive CEA titers were found in the fluids bathing tumors of all 23 patients with colonic carcinoma, 9 of 17 patients with gastric carcinoma, and all 6 patients with pancreatic carcinoma. In contrast, positive CEA titers were found in the plasma of only 16 of 23 patients with colon carcinoma, 6 of 17 patients with gastric carcinoma, and 4 of 6 patients with pancreatic carcinoma. Among 46 patients with gastrointestinal malignancies, CEA was detected in significant concentrations in the plasma of 26 patients and in fluids bathing tumors of 38 patients. These results indicate a significant association of adenocarcinoma of the colon with CEA-positive colonic mucus (P less than 0.01) and suggest the usefulness of assaying CEA in fluids bathing tumors for the detection of gastrointestinal malignancies."} {"id": "PMID:1254137", "title": "Validation and application of a radioimmunoassay for serotonin.", "content": "A radioimmunoassay for serotonin (5-hydroxytryptamine) has been developed, validated, and applied to the measurement of serotonin in blood and platelet-rich plasma. Six rabbits immunized with serotonin diazotized to a DL-p-aminophenylalanine-bovine serum albumin conjugate yielded anti-serotonin antibodies. In the radioimmunoassay, antibody-containing plasma (1:100) is incubated with 0.2 pmoles of [3H]serotonin, EDTA, and either serotonin standards or unknown samples (0.1 ml). Blood levels of serotonin are measured in a protein-free supernatant prepared by water lysis of heparinized blood followed by protein precipitation using zinc hydroxide. This assay is sensitive to 100 pg of serotonin and has demonstrated insignificant cross-reactivity with a number of serotonin analogues at their normal circulating concentrations. Validation has been achieved by obtaining comparable values for normal blood serotonin concentrations by radioimmunoassay and by spectrophotofluorometry as well as by demonstrating that dilutions of endogenous serotonin in rabbit blood and blood from a patient with the carcinoid syndrome were superimposable on a standard calibration curve. In 55 normal human subjects the mean whole blood serotonin concentration was 168 +/- 13.4 ng/ml (mean +/- SEM) (range: 31 to 442 ng/ml). In 15 normal volunteers the mean radioimmunoassayable serotonin concentrations in whole blood and platelet-rich plasma were 337 +/- 40 ng/10(9) platelets and 341 +/- 37 ng/10(9) platelets, respectively. Incubation of blood with PGE1 to inhibit in vitro platelet aggregation before radioimmunoassay resulted in a significant fall in measurable serotonin activity in platelet-poor plasma (from 15.3 +/- 3.0 to 6.4 +/- 1.2 ng/ml). Seventeen normal human volunteers demonstrated a rise in circulating serotonin activity to a mean of 362.1 +/- 16.9 ng/ml at 30 min postcibal after a standard test meal, which was significantly (P less than 0.02) greater than the mean fasting level of 198.1 +/- 37.0 ng/ml. Five fasting controls did not show a rise in circulating serotonin levels when sampled at these intervals. These data suggest release of serotonin, presumably from the intestine, after a meal and make serotonin a candidate hormone in gastrointestinal physiology.", "contents": "Validation and application of a radioimmunoassay for serotonin. A radioimmunoassay for serotonin (5-hydroxytryptamine) has been developed, validated, and applied to the measurement of serotonin in blood and platelet-rich plasma. Six rabbits immunized with serotonin diazotized to a DL-p-aminophenylalanine-bovine serum albumin conjugate yielded anti-serotonin antibodies. In the radioimmunoassay, antibody-containing plasma (1:100) is incubated with 0.2 pmoles of [3H]serotonin, EDTA, and either serotonin standards or unknown samples (0.1 ml). Blood levels of serotonin are measured in a protein-free supernatant prepared by water lysis of heparinized blood followed by protein precipitation using zinc hydroxide. This assay is sensitive to 100 pg of serotonin and has demonstrated insignificant cross-reactivity with a number of serotonin analogues at their normal circulating concentrations. Validation has been achieved by obtaining comparable values for normal blood serotonin concentrations by radioimmunoassay and by spectrophotofluorometry as well as by demonstrating that dilutions of endogenous serotonin in rabbit blood and blood from a patient with the carcinoid syndrome were superimposable on a standard calibration curve. In 55 normal human subjects the mean whole blood serotonin concentration was 168 +/- 13.4 ng/ml (mean +/- SEM) (range: 31 to 442 ng/ml). In 15 normal volunteers the mean radioimmunoassayable serotonin concentrations in whole blood and platelet-rich plasma were 337 +/- 40 ng/10(9) platelets and 341 +/- 37 ng/10(9) platelets, respectively. Incubation of blood with PGE1 to inhibit in vitro platelet aggregation before radioimmunoassay resulted in a significant fall in measurable serotonin activity in platelet-poor plasma (from 15.3 +/- 3.0 to 6.4 +/- 1.2 ng/ml). Seventeen normal human volunteers demonstrated a rise in circulating serotonin activity to a mean of 362.1 +/- 16.9 ng/ml at 30 min postcibal after a standard test meal, which was significantly (P less than 0.02) greater than the mean fasting level of 198.1 +/- 37.0 ng/ml. Five fasting controls did not show a rise in circulating serotonin levels when sampled at these intervals. These data suggest release of serotonin, presumably from the intestine, after a meal and make serotonin a candidate hormone in gastrointestinal physiology."} {"id": "PMID:1254138", "title": "The effects of highly selective vagotomy on exocrine pancreatic function in man.", "content": "Exocrine pancreatic function was studied after meal stimulation and intravenous hormone stimulation with secretin and cholecystokinin in 10 patients with duodenal ulcers before, and 3 to 4 months after, highly selective vagotomy. Hormone stimulation was also performed in 10 healthy volunteers. Meal stimulation test results pre- and postoperatively were not certainly different, but it was concluded that the test technique was inappropriate to the study, not least because no correction of aspirated volumes is possible. Such correction was possible in the intravenous hormone studies. A gastroduodenal tube with a balloon to occlude the pyloric canal was used, and tracer was infused into the duodenum. Results of this latter study showed that patients with duodenal ulcer display an increased basal secretion volume and an increased trypsin output during hormone stimulation. After highly selective vagotomy, basal secretion volume fell, tending to normal, while the stimulated secretion volume and bicarbonate and enzyme output were unchanged.", "contents": "The effects of highly selective vagotomy on exocrine pancreatic function in man. Exocrine pancreatic function was studied after meal stimulation and intravenous hormone stimulation with secretin and cholecystokinin in 10 patients with duodenal ulcers before, and 3 to 4 months after, highly selective vagotomy. Hormone stimulation was also performed in 10 healthy volunteers. Meal stimulation test results pre- and postoperatively were not certainly different, but it was concluded that the test technique was inappropriate to the study, not least because no correction of aspirated volumes is possible. Such correction was possible in the intravenous hormone studies. A gastroduodenal tube with a balloon to occlude the pyloric canal was used, and tracer was infused into the duodenum. Results of this latter study showed that patients with duodenal ulcer display an increased basal secretion volume and an increased trypsin output during hormone stimulation. After highly selective vagotomy, basal secretion volume fell, tending to normal, while the stimulated secretion volume and bicarbonate and enzyme output were unchanged."} {"id": "PMID:1254139", "title": "Effect of first part of duodenum on gastric emptying in dogs: response to acid, fat, glucose, and neural blockade.", "content": "Five dogs were prepared, each with a gastric and duodenal fistula (5 cm distal to the pylorus), to study the inhibitory role of the first 5 cm of the duodenum on gastric emptying. The basic design of the experiments was to instill the test meal (300 ml at 37 degrees C, containing phenol red 40 mg 1(-1)) into the stomach and collect it at 1- or 2-min intervals for 10 or 20 min from the duodenal fistula. As the test meal emptied from the stomach it bathed the first 5 cm of duodenum and thus stimulated the appropriate receptor. A Foley catheter with an inflated balloon prevented passage into the second part of the duodenum. Test meals of hypertonic glucose (15%, 865 milliosmoles kg-1) or 20 and 80 mM of sodium oleate emptied at the same rate as water when allowed to bathe the first 5 cm of duodenum, whereas test meals of 100 mM of HCl were slowed. In further studies using neural blocking agents, the emptying of water meals was slowed with subcutaneous atropine sulfate (0.03 and 0.15 mg kg-1), intravenous hexamethonium chloride (10 mg kg-1), and norepinephrine bitartrate (0.04 mg kg-1). The emptying of 100 to 120 mM HCl meals was slowed by subcutaneous atropine sulfate (0.03 and 0.15 mg kg-1), intravenous norepinephrine bitartrate (0.04 mg kg-1), and the intravenous alpha-receptor blocking agents phenoxybenzamine HCl (2 mg kg-1) and phentolamine (2 mg kg-1), was unaffected by intravenous hexamethonium chloide (10 mg kg-1), and was unchanged (1.0 mg kg-1) or slightly slowed (2.0 mg kg-1) by the beta-receptor blocker propranolol. In contrast, acid test meals were emptied at the same rate as water when treated with intravenous guanethidine monosulfate (2 mg kg-1) or intramuscular reserpine (1 mg kg-1), indicating that the acid inhibition was mediated by an adrenergic mechanism. The emptying of water meals was unchanged by these two drugs. The authors suggest that the first 5 cm of duodenum contain receptors for inhibition of emptying of acid but not for fat or hypertonic glucose. Furthermore, the neural blocking studies indicate that the inhibitory effect of acid in the first part of the duodenum is an adrenergic mechanism which appears to be neither alpha nor beta-receptor-mediated.", "contents": "Effect of first part of duodenum on gastric emptying in dogs: response to acid, fat, glucose, and neural blockade. Five dogs were prepared, each with a gastric and duodenal fistula (5 cm distal to the pylorus), to study the inhibitory role of the first 5 cm of the duodenum on gastric emptying. The basic design of the experiments was to instill the test meal (300 ml at 37 degrees C, containing phenol red 40 mg 1(-1)) into the stomach and collect it at 1- or 2-min intervals for 10 or 20 min from the duodenal fistula. As the test meal emptied from the stomach it bathed the first 5 cm of duodenum and thus stimulated the appropriate receptor. A Foley catheter with an inflated balloon prevented passage into the second part of the duodenum. Test meals of hypertonic glucose (15%, 865 milliosmoles kg-1) or 20 and 80 mM of sodium oleate emptied at the same rate as water when allowed to bathe the first 5 cm of duodenum, whereas test meals of 100 mM of HCl were slowed. In further studies using neural blocking agents, the emptying of water meals was slowed with subcutaneous atropine sulfate (0.03 and 0.15 mg kg-1), intravenous hexamethonium chloride (10 mg kg-1), and norepinephrine bitartrate (0.04 mg kg-1). The emptying of 100 to 120 mM HCl meals was slowed by subcutaneous atropine sulfate (0.03 and 0.15 mg kg-1), intravenous norepinephrine bitartrate (0.04 mg kg-1), and the intravenous alpha-receptor blocking agents phenoxybenzamine HCl (2 mg kg-1) and phentolamine (2 mg kg-1), was unaffected by intravenous hexamethonium chloide (10 mg kg-1), and was unchanged (1.0 mg kg-1) or slightly slowed (2.0 mg kg-1) by the beta-receptor blocker propranolol. In contrast, acid test meals were emptied at the same rate as water when treated with intravenous guanethidine monosulfate (2 mg kg-1) or intramuscular reserpine (1 mg kg-1), indicating that the acid inhibition was mediated by an adrenergic mechanism. The emptying of water meals was unchanged by these two drugs. The authors suggest that the first 5 cm of duodenum contain receptors for inhibition of emptying of acid but not for fat or hypertonic glucose. Furthermore, the neural blocking studies indicate that the inhibitory effect of acid in the first part of the duodenum is an adrenergic mechanism which appears to be neither alpha nor beta-receptor-mediated."} {"id": "PMID:1254140", "title": "Disordered gustatory acuity in liver disease.", "content": "Disordered gustatory acuity was demonstrated in 22 patients with acute viral hepatitis and in 16 patients with chronic liver disease utilizing subjective responses and objective measurements of detection and recognition thresholds and scaling for NaCl, sucrose, HCl, and urea. In patients with early hepatitis and those with chronic liver disease, the magnitude and the uniformity of the threshold elevations were comparable, implying that disordered gustatory acuity reflects disordered hepatic function per se. Patients with acute hepatitis showed a significant fall in taste thresholds (improvement in acuity) as the hepatitis waned, indicating that the gustatory defect is reversible. This disorder of gustatory acuity may contribute to the anorexia commonly found in patients with liver disease.", "contents": "Disordered gustatory acuity in liver disease. Disordered gustatory acuity was demonstrated in 22 patients with acute viral hepatitis and in 16 patients with chronic liver disease utilizing subjective responses and objective measurements of detection and recognition thresholds and scaling for NaCl, sucrose, HCl, and urea. In patients with early hepatitis and those with chronic liver disease, the magnitude and the uniformity of the threshold elevations were comparable, implying that disordered gustatory acuity reflects disordered hepatic function per se. Patients with acute hepatitis showed a significant fall in taste thresholds (improvement in acuity) as the hepatitis waned, indicating that the gustatory defect is reversible. This disorder of gustatory acuity may contribute to the anorexia commonly found in patients with liver disease."} {"id": "PMID:1254141", "title": "Electrophoretic identification of an isoenzyme of amylase which increases in serum in liver diseases.", "content": "Isoenzymes of amylase were studied in serum from 72 persons by means of polyacrylamide gel electrophoresis and a direct saccharogenic assay for amylase activity. In 37 normal individuals, there were two major peaks of amylase actvity with mobilities similar to pancreatic and salivary amylases. In 11 patiets with acute pancreatitis, the area of activity corresponding with pancreatic amylases increased disproportionately. Electrophoretic patterns of amylase activity in normal and pancreatitis urine were almost identical to the respective serum patterns from the same persons. In contrast, a prominent slower-moving peak of amylase activity occurred in the serum of 8 of 12 patients who had hyperamylasemia associated with various liver diseases. Traces of this third peak were identifiable in one-third of normal serum specimens, but no increases in its activity were observed in any specimen from 11 patients with pancreatitis or from 12 other patients with hyperamylasemia unassociated with liver disease. The slower-moving peak was absent from the urine of patients whose serum contained it. The origin of the slower-moving serum amylase appearing in patients with liver disease is not established by these studies. It is possible either that a hepatic amylase is liberated from damaged liver cells or that the metabolism of an amylase not originating in the liver is altered as a result of liver dysfunction.", "contents": "Electrophoretic identification of an isoenzyme of amylase which increases in serum in liver diseases. Isoenzymes of amylase were studied in serum from 72 persons by means of polyacrylamide gel electrophoresis and a direct saccharogenic assay for amylase activity. In 37 normal individuals, there were two major peaks of amylase actvity with mobilities similar to pancreatic and salivary amylases. In 11 patiets with acute pancreatitis, the area of activity corresponding with pancreatic amylases increased disproportionately. Electrophoretic patterns of amylase activity in normal and pancreatitis urine were almost identical to the respective serum patterns from the same persons. In contrast, a prominent slower-moving peak of amylase activity occurred in the serum of 8 of 12 patients who had hyperamylasemia associated with various liver diseases. Traces of this third peak were identifiable in one-third of normal serum specimens, but no increases in its activity were observed in any specimen from 11 patients with pancreatitis or from 12 other patients with hyperamylasemia unassociated with liver disease. The slower-moving peak was absent from the urine of patients whose serum contained it. The origin of the slower-moving serum amylase appearing in patients with liver disease is not established by these studies. It is possible either that a hepatic amylase is liberated from damaged liver cells or that the metabolism of an amylase not originating in the liver is altered as a result of liver dysfunction."} {"id": "PMID:1254142", "title": "A refractory case of hepatic amoebiasis.", "content": "A 39-year-old man had three separate episodes of hepatic amoebiasis despite one course of emetine and chloroquine, two courses of metronidazole, and one prolonged course of chloroquine. Asymptomatic intestinal amoebiasis was first detected after his third episode of hepatic disease, and his eventual cure followed an intensive regimen designed primarily to treat the intestinal infection. It seems likely that the intestinal amoebiasis had been present undetected since the onset of hepatic disease and had served as the source for reinfection of the liver.", "contents": "A refractory case of hepatic amoebiasis. A 39-year-old man had three separate episodes of hepatic amoebiasis despite one course of emetine and chloroquine, two courses of metronidazole, and one prolonged course of chloroquine. Asymptomatic intestinal amoebiasis was first detected after his third episode of hepatic disease, and his eventual cure followed an intensive regimen designed primarily to treat the intestinal infection. It seems likely that the intestinal amoebiasis had been present undetected since the onset of hepatic disease and had served as the source for reinfection of the liver."} {"id": "PMID:1254143", "title": "Spontaneous hepatic artery thrombosis with infarction of the liver.", "content": "Extensive infarction of the liver, initially thought to be halothane hepatitis, is described. The patient developed severe right upper quadrant abdominal pain and abnormal liver function tests after amputation of the leg. The correct diagnosis was made by percutaneous needle biopsy of the liver which demonstrated a large area of avascular necrosis. The patient recovered, indicating the remarkable ability of the liver to maintain function despite ischemic injury. The patient died later from an acute myocardial infarction, and at autopsy thrombosis of the hepatic artery and multiple hepatic infarcts were confirmed.", "contents": "Spontaneous hepatic artery thrombosis with infarction of the liver. Extensive infarction of the liver, initially thought to be halothane hepatitis, is described. The patient developed severe right upper quadrant abdominal pain and abnormal liver function tests after amputation of the leg. The correct diagnosis was made by percutaneous needle biopsy of the liver which demonstrated a large area of avascular necrosis. The patient recovered, indicating the remarkable ability of the liver to maintain function despite ischemic injury. The patient died later from an acute myocardial infarction, and at autopsy thrombosis of the hepatic artery and multiple hepatic infarcts were confirmed."} {"id": "PMID:1254155", "title": "[The diagnosis of corpus carcinoma (Differentialdiagnostic importance of history- and clinical criteria in post-menopausal hemorrhage) (author's transl)].", "content": "Among 1554 patients with post-memopausal hemorrhage over 7 years one half were due to benign causes, the other in almost equal parts to carcinoma of the fundus or cervix. Ca of the fundus is more likely when post-menopausal bleeding occurs at a relatively old age, a late menopause and a long interval between menopause and post-menopausal bleeding. Nulliparae more often have Ca of the corpus than in the cervix or have benign changes. The trias known for the corpus Ca: adiposity, diabetes and hypertension is confirmed. An enlargement or softening of the uterus and myomatous changes also indicate Ca. Anatomical and clinical criteria permit not only a detailed assessment of post-menopausal bleeding but also a definition of cases at risk before bleeding occurs and give an indication for detailed investigations.", "contents": "[The diagnosis of corpus carcinoma (Differentialdiagnostic importance of history- and clinical criteria in post-menopausal hemorrhage) (author's transl)]. Among 1554 patients with post-memopausal hemorrhage over 7 years one half were due to benign causes, the other in almost equal parts to carcinoma of the fundus or cervix. Ca of the fundus is more likely when post-menopausal bleeding occurs at a relatively old age, a late menopause and a long interval between menopause and post-menopausal bleeding. Nulliparae more often have Ca of the corpus than in the cervix or have benign changes. The trias known for the corpus Ca: adiposity, diabetes and hypertension is confirmed. An enlargement or softening of the uterus and myomatous changes also indicate Ca. Anatomical and clinical criteria permit not only a detailed assessment of post-menopausal bleeding but also a definition of cases at risk before bleeding occurs and give an indication for detailed investigations."} {"id": "PMID:1254156", "title": "[Cytology of mamma-secretion -- results at a laboratory (author's transl)].", "content": "Results of cytological examination of mammasecretion in 1252 patients are analyzed. 85.2% were negative. 30 patients (2.4%) showed a suspect or positive result. Of 22 biopsies 9 showed histologically a carcinoma, in the others there were proliferative changes. In contrast there were 3 cases of mamma carcinoma in whom cytology was negative. In all these clinical and mammographic findings gave proof. The possibility of negative histologic results combined with positive cytology is shown to be due to inexpert biopsy. Comparing results with galactography, cytology of mammasecretion which is pathologic is recommended as an additional technique.", "contents": "[Cytology of mamma-secretion -- results at a laboratory (author's transl)]. Results of cytological examination of mammasecretion in 1252 patients are analyzed. 85.2% were negative. 30 patients (2.4%) showed a suspect or positive result. Of 22 biopsies 9 showed histologically a carcinoma, in the others there were proliferative changes. In contrast there were 3 cases of mamma carcinoma in whom cytology was negative. In all these clinical and mammographic findings gave proof. The possibility of negative histologic results combined with positive cytology is shown to be due to inexpert biopsy. Comparing results with galactography, cytology of mammasecretion which is pathologic is recommended as an additional technique."} {"id": "PMID:1254157", "title": "[The problems of prophylactic chemotherapy, the second-look operation and the maintenance of the remission in the treatment of ovarian cancer (author's transl)].", "content": "The results of the treatment of 1022 ovarian cancers were reviewed and the problems of prophylactic chemotherapy, a second look operation and the maintenance of the remission were studied. In ovarian cancers of stage 1 and stage 2, a post-operative prophylactic chemotherapy is useful only in cases with tumor cells in the secretions of the pouch of Douglas or in the ascites and in cases where a sensitivity to the chemotherapy can be assumed. In about 50% of primarily inoperable stage 3 ovarian cancers, the random treatment with cyclophosphamide (Endoxan) results in a clinical remission. A significant five year cure rate can only be obtained if the uterus and the adnexa are removed. Radical operation during the remission appears to be very important for survival of the patient. For the maintenance of the remission continuous chemotherapy for at least 2 years following treatment by operation and radiotherapy is necessary.", "contents": "[The problems of prophylactic chemotherapy, the second-look operation and the maintenance of the remission in the treatment of ovarian cancer (author's transl)]. The results of the treatment of 1022 ovarian cancers were reviewed and the problems of prophylactic chemotherapy, a second look operation and the maintenance of the remission were studied. In ovarian cancers of stage 1 and stage 2, a post-operative prophylactic chemotherapy is useful only in cases with tumor cells in the secretions of the pouch of Douglas or in the ascites and in cases where a sensitivity to the chemotherapy can be assumed. In about 50% of primarily inoperable stage 3 ovarian cancers, the random treatment with cyclophosphamide (Endoxan) results in a clinical remission. A significant five year cure rate can only be obtained if the uterus and the adnexa are removed. Radical operation during the remission appears to be very important for survival of the patient. For the maintenance of the remission continuous chemotherapy for at least 2 years following treatment by operation and radiotherapy is necessary."} {"id": "PMID:1254158", "title": "[The clinical significance of deficiency coagulopathy in relationship to consumption coagulopathy (authors' transl)].", "content": "A deficiency coagulopathy may lead to a coagulation defect in the presence of massive blood loss which is characterized by a dilution of the coagulation factors especially a dilution of the plasma fibrinogen and the platelets and a dilution of their function. Hemorrhages which are triggered by a coagulation defect (consumption coagulopathy) may be aggravated by the additional loss of coagulation factors. The combination of a coagulation coagulopathy with a deficiency coagulopathy results in a bad prognosis. A case of deficiency coagulopathy and a case of consumption coagulopathy with additional deficiency coagulopathy are reported, the clinical importance and the management of these conditions are discussed.", "contents": "[The clinical significance of deficiency coagulopathy in relationship to consumption coagulopathy (authors' transl)]. A deficiency coagulopathy may lead to a coagulation defect in the presence of massive blood loss which is characterized by a dilution of the coagulation factors especially a dilution of the plasma fibrinogen and the platelets and a dilution of their function. Hemorrhages which are triggered by a coagulation defect (consumption coagulopathy) may be aggravated by the additional loss of coagulation factors. The combination of a coagulation coagulopathy with a deficiency coagulopathy results in a bad prognosis. A case of deficiency coagulopathy and a case of consumption coagulopathy with additional deficiency coagulopathy are reported, the clinical importance and the management of these conditions are discussed."} {"id": "PMID:1254159", "title": "[Experimental and clinical investigations on the effects of carbon dioxide gas during hysteroscopy (author's transl)].", "content": "The acute toxicity, lethal dosage and mechanical effects of carbon dioxide gas were studied in the waking dog by intravenous and intra-arterial insufflation. The threshold dosage for toxicity was 400 ml per minute in the dog. The important factor in the toxicity was not the total volume of carbon dioxide but the volume per unit of time. Metabolic acidosis was responsible for changes in the EKG, the heart rate and the respiratory rate. These findings are discussed in relationship to the usage of carbon dioxide gas for hysteroscopy in the human female. During carbon dioxide gas hysteroscopy blood gas analyses were done in 40 patients. 28 patients had a hysteroscopy under general anaesthesia and 12 patients under local anaesthesia. It was found that the volume of carbon dioxide used for the creation of a pneumometra in hysteroscopy has no side effect. The necessary gas flow is too small for toxic side effects or mechanical side effects such as a gas embolisation.", "contents": "[Experimental and clinical investigations on the effects of carbon dioxide gas during hysteroscopy (author's transl)]. The acute toxicity, lethal dosage and mechanical effects of carbon dioxide gas were studied in the waking dog by intravenous and intra-arterial insufflation. The threshold dosage for toxicity was 400 ml per minute in the dog. The important factor in the toxicity was not the total volume of carbon dioxide but the volume per unit of time. Metabolic acidosis was responsible for changes in the EKG, the heart rate and the respiratory rate. These findings are discussed in relationship to the usage of carbon dioxide gas for hysteroscopy in the human female. During carbon dioxide gas hysteroscopy blood gas analyses were done in 40 patients. 28 patients had a hysteroscopy under general anaesthesia and 12 patients under local anaesthesia. It was found that the volume of carbon dioxide used for the creation of a pneumometra in hysteroscopy has no side effect. The necessary gas flow is too small for toxic side effects or mechanical side effects such as a gas embolisation."} {"id": "PMID:1254160", "title": "[On the optimal method of delivery in breech presentation (author's transl)].", "content": "Between 1966 and 1974, 90% of 581 single breech presentations were delivered vaginally. The incidence of Caesarean Section was 9.5%. The overall perinatal mortality was 14%. After elimination of premature deliveries under 1000 grams, stillbirth prior to labour and non-viable anomalies, the perinatal mortality was 5.6%. The perinatal mortality in infants over 2500 grams was 0.69%.", "contents": "[On the optimal method of delivery in breech presentation (author's transl)]. Between 1966 and 1974, 90% of 581 single breech presentations were delivered vaginally. The incidence of Caesarean Section was 9.5%. The overall perinatal mortality was 14%. After elimination of premature deliveries under 1000 grams, stillbirth prior to labour and non-viable anomalies, the perinatal mortality was 5.6%. The perinatal mortality in infants over 2500 grams was 0.69%."} {"id": "PMID:1254161", "title": "[Dignity of morgagni hydatids (scanning-electronoptical and light-optical investigations (author's transl)].", "content": "Scanning-electronoptical and light-optical investigations were performed on 25 Morgagni-hydatids being a special type of parovarial cysts and not descending from the Fallopian tube. An epithelium similar to that of the Fallopian tube was found not depending to cyclic changes. In one case atypical papillary growth with disorder in cellular differentiation causing in an increased proliferation could be demonstrated. As hydatids belong to parovarial cysts, they may become malignant and therefore should be exstirpated in any case.", "contents": "[Dignity of morgagni hydatids (scanning-electronoptical and light-optical investigations (author's transl)]. Scanning-electronoptical and light-optical investigations were performed on 25 Morgagni-hydatids being a special type of parovarial cysts and not descending from the Fallopian tube. An epithelium similar to that of the Fallopian tube was found not depending to cyclic changes. In one case atypical papillary growth with disorder in cellular differentiation causing in an increased proliferation could be demonstrated. As hydatids belong to parovarial cysts, they may become malignant and therefore should be exstirpated in any case."} {"id": "PMID:1254162", "title": "[Cervical perforation due to a copper-T device placed following abortion (author's transl)].", "content": "Report on a patient who had a Copper-T intrauterine device placed following abortion. The vertical arm of the device perforated the cervix and resulted in cervicitis and endometritis.", "contents": "[Cervical perforation due to a copper-T device placed following abortion (author's transl)]. Report on a patient who had a Copper-T intrauterine device placed following abortion. The vertical arm of the device perforated the cervix and resulted in cervicitis and endometritis."} {"id": "PMID:1254213", "title": "[Ski boots from an orthopedic point of view].", "content": "1. A ski-boot should have an adequate arch support and a variable, as well as an exact fitting of the dorsal part. This can be achieved with flow, foam, air or wax. 2. Isolated pressure of compression systems of different kinds should be avoided (e.g. pressure of buckles above the ankle). New results are demonstrated by the possibility of putting on the boot from behind and having the buckles at the back of the boot. 3. The strap from ankle to foot has to be continuous to avoid pressure points. 4. It should be possible to walk and stand in a ski-boot without either muscular strain or pressure on the knee-joint. In addition, the sole has to give an optimal grip also on icy ground to prevent slipping.", "contents": "[Ski boots from an orthopedic point of view]. 1. A ski-boot should have an adequate arch support and a variable, as well as an exact fitting of the dorsal part. This can be achieved with flow, foam, air or wax. 2. Isolated pressure of compression systems of different kinds should be avoided (e.g. pressure of buckles above the ankle). New results are demonstrated by the possibility of putting on the boot from behind and having the buckles at the back of the boot. 3. The strap from ankle to foot has to be continuous to avoid pressure points. 4. It should be possible to walk and stand in a ski-boot without either muscular strain or pressure on the knee-joint. In addition, the sole has to give an optimal grip also on icy ground to prevent slipping."} {"id": "PMID:1254214", "title": "[Ski boot rim fracture: tension-optical study].", "content": "Most of the models of ski-boots used today end up at the weakest area of the tibia. They should be disregarded for medical and statistical reasons because the maximal bending point lies at the minimal diameter of the tibia. A ski-boot with a joint, splinting more than the distal third of the calf and ending approximately at the mid-point of the tibia elasticity, offers an important safety to the skier. Together with a safety binding the risk of an accident of the so-called \"fracture of the border of the ski-boot\" can be further reduced.", "contents": "[Ski boot rim fracture: tension-optical study]. Most of the models of ski-boots used today end up at the weakest area of the tibia. They should be disregarded for medical and statistical reasons because the maximal bending point lies at the minimal diameter of the tibia. A ski-boot with a joint, splinting more than the distal third of the calf and ending approximately at the mid-point of the tibia elasticity, offers an important safety to the skier. Together with a safety binding the risk of an accident of the so-called \"fracture of the border of the ski-boot\" can be further reduced."} {"id": "PMID:1254215", "title": "[The fatal ski accident].", "content": "This investigation analyzes 18 fatal skiing accidents which happened from 1959 to 1975. Deadly accidents caused by avalanches were not taken into consideration. The results of the authors were compared with reports of altogether sixty similar injuries due to skiing accidents. 46% of the fatal accidents were caused by crashing against hindrances. Half of the accidents happened during high-speed-skiing or downhill-competition. More than two-thirds of the wounded skiers died of head injuries. Therefore it is highly recommended to wear a suitable headprotection while skiing downhill.", "contents": "[The fatal ski accident]. This investigation analyzes 18 fatal skiing accidents which happened from 1959 to 1975. Deadly accidents caused by avalanches were not taken into consideration. The results of the authors were compared with reports of altogether sixty similar injuries due to skiing accidents. 46% of the fatal accidents were caused by crashing against hindrances. Half of the accidents happened during high-speed-skiing or downhill-competition. More than two-thirds of the wounded skiers died of head injuries. Therefore it is highly recommended to wear a suitable headprotection while skiing downhill."} {"id": "PMID:1254216", "title": "[Appendicitis in infants].", "content": "Results from cases of appendicitis occurring during the first three years of life are compared with those found in the literature. In the Departments of Surgery and Paediatrics in the University of K\u00f6ln-Lindenthal 26 cases of appendicitis occurred in this age group between 1960 and 1975. The majority of cases were of the advanced forms of the disease in which the appendix was already perforated. Successful operations were performed in 25 children, but in a 12-day old infant the disease was diagnosed only at autopsy. An early diagnosis is imperative, and can only be deduced from a thorough diagnosis and compilation of symptoms.", "contents": "[Appendicitis in infants]. Results from cases of appendicitis occurring during the first three years of life are compared with those found in the literature. In the Departments of Surgery and Paediatrics in the University of K\u00f6ln-Lindenthal 26 cases of appendicitis occurred in this age group between 1960 and 1975. The majority of cases were of the advanced forms of the disease in which the appendix was already perforated. Successful operations were performed in 25 children, but in a 12-day old infant the disease was diagnosed only at autopsy. An early diagnosis is imperative, and can only be deduced from a thorough diagnosis and compilation of symptoms."} {"id": "PMID:1254219", "title": "[Chronic posttraumatic osteomyelitis. 2. Circulation problems].", "content": "Blood volume and total body water was determined in 20 patients suffering from chronic posttraumatic osteomyelitis and compared to the values from 15 healthy volunteers. Only patients who were unable to leave the bed, showed a marked decrease in circulating blood volume of more than 10%. Total body water remained essentially unchanged.", "contents": "[Chronic posttraumatic osteomyelitis. 2. Circulation problems]. Blood volume and total body water was determined in 20 patients suffering from chronic posttraumatic osteomyelitis and compared to the values from 15 healthy volunteers. Only patients who were unable to leave the bed, showed a marked decrease in circulating blood volume of more than 10%. Total body water remained essentially unchanged."} {"id": "PMID:1254220", "title": "[Biodynamics of the hip joint. The elasticity of the human femur and its importance].", "content": "Pauwels' biomechanical analysis of hip joint function shows that the dynamic forces acting on the joint can be large. In these techniques, spring mechanisms are being used to neutralize dynamic forces. The question remains as to whether such a mechanism in humans exists in the vicinity of the hip joint, i.e. in the femur. Fresh human femoral bones were put under axial stress and their qualities examined. Different spring qualities were found in the various femora; and by comparing these, 6 groups were established which were then subjected to statistical analysis. More than half the bones examined possessed good spring qualities. A practical example proves that the spring qualities of the femur are apt to absorb a considerable amount of kinetic energy during the axial stress and thus lessen the vertical mechanical strain vector of the hip joint.", "contents": "[Biodynamics of the hip joint. The elasticity of the human femur and its importance]. Pauwels' biomechanical analysis of hip joint function shows that the dynamic forces acting on the joint can be large. In these techniques, spring mechanisms are being used to neutralize dynamic forces. The question remains as to whether such a mechanism in humans exists in the vicinity of the hip joint, i.e. in the femur. Fresh human femoral bones were put under axial stress and their qualities examined. Different spring qualities were found in the various femora; and by comparing these, 6 groups were established which were then subjected to statistical analysis. More than half the bones examined possessed good spring qualities. A practical example proves that the spring qualities of the femur are apt to absorb a considerable amount of kinetic energy during the axial stress and thus lessen the vertical mechanical strain vector of the hip joint."} {"id": "PMID:1254221", "title": "[The hip joint arthrodesis. A clinical and experimental study on the effective ankylosis of the hip joint].", "content": "It could be demonstrated by clinical, electromyographical, biomechanical and experimental investigations that only a flexed position of 25-30 degrees in medial position between abduction and adduction and in an external rotated position of 5-10 degrees of arthrodesis of the hip the impairment of the periankylotic locomotor centers is minimal.", "contents": "[The hip joint arthrodesis. A clinical and experimental study on the effective ankylosis of the hip joint]. It could be demonstrated by clinical, electromyographical, biomechanical and experimental investigations that only a flexed position of 25-30 degrees in medial position between abduction and adduction and in an external rotated position of 5-10 degrees of arthrodesis of the hip the impairment of the periankylotic locomotor centers is minimal."} {"id": "PMID:1254222", "title": "[The fiberglass dressing with a hinge and its value in the care of ski injuries].", "content": "Casts for immobilisation of a limb with an artificial external joint can be made light and stable using fiberglass material, because the application of a joint is possible with less material as it is possible using a conventional cast.", "contents": "[The fiberglass dressing with a hinge and its value in the care of ski injuries]. Casts for immobilisation of a limb with an artificial external joint can be made light and stable using fiberglass material, because the application of a joint is possible with less material as it is possible using a conventional cast."} {"id": "PMID:1254227", "title": "[Hormonal regulation of human mammary function].", "content": "This review summarises our present knowledge on the endocrine aspects of human mammary function. The fact is stressed that much of the knowledge on mammary function is based on animal studies, and therefore caution must be exercised in drawing conclusions as to mammary function in humans from such experiments. Some recent aspects of mammary function especially in humans are also summarised, as evaluated through 2-bromo-alpha-ergocryptine (CB 154). Special emphasis is placed upon the role of prolactin in the initiation and maintenance of human lactation, some phylogenetic aspects of this hormone are also discussed.", "contents": "[Hormonal regulation of human mammary function]. This review summarises our present knowledge on the endocrine aspects of human mammary function. The fact is stressed that much of the knowledge on mammary function is based on animal studies, and therefore caution must be exercised in drawing conclusions as to mammary function in humans from such experiments. Some recent aspects of mammary function especially in humans are also summarised, as evaluated through 2-bromo-alpha-ergocryptine (CB 154). Special emphasis is placed upon the role of prolactin in the initiation and maintenance of human lactation, some phylogenetic aspects of this hormone are also discussed."} {"id": "PMID:1254230", "title": "[Chronic posttraumatic ostemyelitis. 3. Immunopathological aspects].", "content": "3. Immunological aspects 90 patients suffering from chronic posttraumatic osteomyelitis were examined immunologically. In 10-20% of the patients serum immunoglobulin levels were changed. Only 45% of the patients with staphylococcal infection had a positive anti-staphylolysin titer. In 10% of the patients so-called wound-specific antibodies were demonstrated; their possible autoimmune origin is discussed. A comparison of three groups of patients according to the immunological reactivity \"hypoimmune\", \"humoral hyper-immune\" and \"cellular hyperimmune\" showed that the worst clinical courses were observed in patinets with established delayed type hypersensitivity.", "contents": "[Chronic posttraumatic ostemyelitis. 3. Immunopathological aspects]. 3. Immunological aspects 90 patients suffering from chronic posttraumatic osteomyelitis were examined immunologically. In 10-20% of the patients serum immunoglobulin levels were changed. Only 45% of the patients with staphylococcal infection had a positive anti-staphylolysin titer. In 10% of the patients so-called wound-specific antibodies were demonstrated; their possible autoimmune origin is discussed. A comparison of three groups of patients according to the immunological reactivity \"hypoimmune\", \"humoral hyper-immune\" and \"cellular hyperimmune\" showed that the worst clinical courses were observed in patinets with established delayed type hypersensitivity."} {"id": "PMID:1254238", "title": "[Anorectal manometry. A new method for the evaluation of continence, incontinence and chronic constipation].", "content": "643 ano-rectal electromanometric investigations were carried out in 438 children with different ano-rectal diseases including myelomeningocele, Hirschsprung's disease, anal atresia and chronic constipation, as well as in healthy premature, new-born and older infants. The reliability of the recorded physiological and pathological parameters was found to be significant in 87,2%. Electromanometry is shown to be an important new method of assessing ano-rectal continence.", "contents": "[Anorectal manometry. A new method for the evaluation of continence, incontinence and chronic constipation]. 643 ano-rectal electromanometric investigations were carried out in 438 children with different ano-rectal diseases including myelomeningocele, Hirschsprung's disease, anal atresia and chronic constipation, as well as in healthy premature, new-born and older infants. The reliability of the recorded physiological and pathological parameters was found to be significant in 87,2%. Electromanometry is shown to be an important new method of assessing ano-rectal continence."} {"id": "PMID:1254239", "title": "[Adenomatous hyperplasia of the corpus endometrium and the endocervix. Origin, severity and therapy].", "content": "An excessive endogenous or exogenous stimulation by estrogen induces adenomatous hyperplasia of the endometrium. The age of the patient and the origin of the estrogenic stimulus however influence the morphology of the hyperplasia. Those resulting from exogenous estrogen rapidly regress after the estrogen is discontinued. To cure hyperplasias brought on by endogenous estrogen, however, therapy with high doses of gestagen is required.", "contents": "[Adenomatous hyperplasia of the corpus endometrium and the endocervix. Origin, severity and therapy]. An excessive endogenous or exogenous stimulation by estrogen induces adenomatous hyperplasia of the endometrium. The age of the patient and the origin of the estrogenic stimulus however influence the morphology of the hyperplasia. Those resulting from exogenous estrogen rapidly regress after the estrogen is discontinued. To cure hyperplasias brought on by endogenous estrogen, however, therapy with high doses of gestagen is required."} {"id": "PMID:1254240", "title": "[Chronic posttraumatic osteomyelitis. Attempt at oral autovaccine therapy].", "content": "18 patients suffering from chronic posttraumatic osteomyelitis were treated by oral autovaccination. 11 patients showed significant improvement of clinical condition. The therapeutic effect was evaluated by a scoring system considering the wound morphology, the bone radiology and the erythrocyte sedimentation rate. The most pronounced clinical improvements were observed in patients with established delayed type hypersensitivity against staphylococci.", "contents": "[Chronic posttraumatic osteomyelitis. Attempt at oral autovaccine therapy]. 18 patients suffering from chronic posttraumatic osteomyelitis were treated by oral autovaccination. 11 patients showed significant improvement of clinical condition. The therapeutic effect was evaluated by a scoring system considering the wound morphology, the bone radiology and the erythrocyte sedimentation rate. The most pronounced clinical improvements were observed in patients with established delayed type hypersensitivity against staphylococci."} {"id": "PMID:1254242", "title": "[Therapeutic results with delta tomanol B, a new form of the so-called \"Tubingen bomb\". Experiences from a general practice].", "content": "98 patients suffering from spinal syndromes, acute inflammatory arthropathies, neuritides and one case of polyneuropathy were treated with Delta-Tomanol B. As a result, it can be stated that Delta-Tomanol B provides a quick analgesia and, in general a good therapeutic effect with an excellent tolerance. It should be stressed moreover that the mode of application of Delta-Tomanol B, which contains 4 active principles in a stable solution for injections (3 ml!) is very simple: but one ampule has to be opened and drawn up. This is an important advantage of Delta-Tomanol B in comparison with the existing comparable preparations.", "contents": "[Therapeutic results with delta tomanol B, a new form of the so-called \"Tubingen bomb\". Experiences from a general practice]. 98 patients suffering from spinal syndromes, acute inflammatory arthropathies, neuritides and one case of polyneuropathy were treated with Delta-Tomanol B. As a result, it can be stated that Delta-Tomanol B provides a quick analgesia and, in general a good therapeutic effect with an excellent tolerance. It should be stressed moreover that the mode of application of Delta-Tomanol B, which contains 4 active principles in a stable solution for injections (3 ml!) is very simple: but one ampule has to be opened and drawn up. This is an important advantage of Delta-Tomanol B in comparison with the existing comparable preparations."} {"id": "PMID:1254243", "title": "Human high denisty apolipoprotein A-I-lysolecithin-lecithin and sphingomyelin complexes. A method for high yield recombinations to lipoprotein complexes of reproducible stoichiometry.", "content": "High denisty apolipoprotein A-1 (apoLp A-I) has been prepared in a chromatographically and immunochemically homogeneous form. This apoprotein forms trimeric and tetrameric aggregates in aqueous solutions at higher concentrations. ApoLp A-I has been recombined in almost quantitative yield in the presence of lysolecithin with phosphatidylcholine and sphingomyelin to particles of reproducible stoichiometry. Lysolecithin is not required for the interactions of lecithin and sphingomyelin with the apoprotein A-I or for the stability of these complexes. Dialysis removes most of the lysolecithin without the loss of lecithin and sphingomyelin. ApoLp A-I-lecithin particles have a molecular weight of 200 000 and contain 50 molecules lecithin and 25 of lysolecithin. ApoLp A-I-sphingomyelin complexes contain 50 sphingomyelin and 13 lysolecithin molecules. The former particles show up as discs of 100 A diameter, and the latter particles are 250 A in diameter. Their thickness was estimated as 25 A in the apoLp A-I lecithin and 60 A in the apoLp A-I-sphingomyelin particles. ApoLp A-I and lysolecithin form complexes whose densities depend on the lysolecithin concentration. Lysolecithin enhances the binding of phosphatidylcholine to apoLP A-I, yielding lipoprotein complexes with decreasing density. The yield of apoLp A-I-sphingomyelin-lysolecithin complexes is proportional to the lysolecithin concentration. The ratio of apoLp A-I to sphingomyelin in all these complexes remains constant.", "contents": "Human high denisty apolipoprotein A-I-lysolecithin-lecithin and sphingomyelin complexes. A method for high yield recombinations to lipoprotein complexes of reproducible stoichiometry. High denisty apolipoprotein A-1 (apoLp A-I) has been prepared in a chromatographically and immunochemically homogeneous form. This apoprotein forms trimeric and tetrameric aggregates in aqueous solutions at higher concentrations. ApoLp A-I has been recombined in almost quantitative yield in the presence of lysolecithin with phosphatidylcholine and sphingomyelin to particles of reproducible stoichiometry. Lysolecithin is not required for the interactions of lecithin and sphingomyelin with the apoprotein A-I or for the stability of these complexes. Dialysis removes most of the lysolecithin without the loss of lecithin and sphingomyelin. ApoLp A-I-lecithin particles have a molecular weight of 200 000 and contain 50 molecules lecithin and 25 of lysolecithin. ApoLp A-I-sphingomyelin complexes contain 50 sphingomyelin and 13 lysolecithin molecules. The former particles show up as discs of 100 A diameter, and the latter particles are 250 A in diameter. Their thickness was estimated as 25 A in the apoLp A-I lecithin and 60 A in the apoLp A-I-sphingomyelin particles. ApoLp A-I and lysolecithin form complexes whose densities depend on the lysolecithin concentration. Lysolecithin enhances the binding of phosphatidylcholine to apoLP A-I, yielding lipoprotein complexes with decreasing density. The yield of apoLp A-I-sphingomyelin-lysolecithin complexes is proportional to the lysolecithin concentration. The ratio of apoLp A-I to sphingomyelin in all these complexes remains constant."} {"id": "PMID:1254244", "title": "[On uroporphyrinogen formation: Studies with 1-aminomethyl-3, 8, 13, 18-tetra(2-carboxyethyl)-2, 7, 12, 17-tetracarboxymethylbilinogen (author's transl)].", "content": "The preparation of the aminomethyl-bilinogen which results from formal \"head to tail\" condensation of porphobilinogen is described. The chemical cyclocondensation of this compound at pH 7.4 yields uroporphyrinogen I. Enzymatic studies with enzyme preparations from Propionibacterium shermanii, which synthesize uroporphyrinogens from porphobilinogen, show that the rate of cyclisation is increased by these enzymes and indicate that the bilinogen also might be used for uroporphyrinogen III formation. This is also suggested by studies on the formation of cobyrinic acid from [4-14C]5-aminolevulinate via uroporphyrinogen III in the presence of the aminomethylbilinogen by cell-free extracts from Clostridium tetanomorphum.", "contents": "[On uroporphyrinogen formation: Studies with 1-aminomethyl-3, 8, 13, 18-tetra(2-carboxyethyl)-2, 7, 12, 17-tetracarboxymethylbilinogen (author's transl)]. The preparation of the aminomethyl-bilinogen which results from formal \"head to tail\" condensation of porphobilinogen is described. The chemical cyclocondensation of this compound at pH 7.4 yields uroporphyrinogen I. Enzymatic studies with enzyme preparations from Propionibacterium shermanii, which synthesize uroporphyrinogens from porphobilinogen, show that the rate of cyclisation is increased by these enzymes and indicate that the bilinogen also might be used for uroporphyrinogen III formation. This is also suggested by studies on the formation of cobyrinic acid from [4-14C]5-aminolevulinate via uroporphyrinogen III in the presence of the aminomethylbilinogen by cell-free extracts from Clostridium tetanomorphum."} {"id": "PMID:1254245", "title": "Plant microbody proteins. II. Purification and characterization of the major protein component (SP-63) of peroxisome membranes.", "content": "The major component of membranes of microbodies from green leaves of Lens culinaris is a protein of a subunit molecular weight of 63 000. This protein, referred to as SP-63, seems to be unique to microbodies and could not be detected when plastids or mitochondria were analyzed. It is probably a structural protein and is thus not solubilized by cholate, Triton X-100, chloroform/methanol, or 0.2M KCl. Solubilization from purified membranes was achieved with guanidinium chloride or sodium dodecylsulphate. The protein was separated from minor contaminating components by chromatography on Sepharose 4B or Sephadex G-150 employing 0.1% sodium dodecylsulphate or 4M urea as eluent. It was shown to be homogeneous upon sodium dodecylsulphate gel electrophoresis and did not give a positive glycoprotein stain.", "contents": "Plant microbody proteins. II. Purification and characterization of the major protein component (SP-63) of peroxisome membranes. The major component of membranes of microbodies from green leaves of Lens culinaris is a protein of a subunit molecular weight of 63 000. This protein, referred to as SP-63, seems to be unique to microbodies and could not be detected when plastids or mitochondria were analyzed. It is probably a structural protein and is thus not solubilized by cholate, Triton X-100, chloroform/methanol, or 0.2M KCl. Solubilization from purified membranes was achieved with guanidinium chloride or sodium dodecylsulphate. The protein was separated from minor contaminating components by chromatography on Sepharose 4B or Sephadex G-150 employing 0.1% sodium dodecylsulphate or 4M urea as eluent. It was shown to be homogeneous upon sodium dodecylsulphate gel electrophoresis and did not give a positive glycoprotein stain."} {"id": "PMID:1254246", "title": "Further studies on the three-step-increase in activity due to the aromatic amino acids B24-26 (-Phe-Phe-Tyr-).", "content": "Using a reaction suite which was suggested by Ruttenberg [5] for the semisynthesis of insulin variants, insulin hexamethyl ester was digested by trypsin, then the N-terminal amino groups of the resulting desoctapeptide insulin pentamethyl ester were protected with the Boc residue. The free carboxyl group of the arginyl residue (B22) of this product was coupled to two different series of synthetic peptide methyl esters: I) Gly-OMe, Gly-Phe-OMe, Gly-Phe-Phe-OMe, Gly-Phe-Phe-Tyr-OMe and II) Gly-Ala-OMe, Gly-Phe-Ala-OMe, Gly-Phe-Phe-Ala-OMe, Gly-Phe-Phe-Tyr-Ala-OMe. Removal of all protecting groups yielded the corresponding insulin variants. The syntheses of these peptide methyl esters are described. Following the original prescription of Ruttenberg[5], we were not able to prepare the desired variants. That is why we were forced to change some important details of the Ruttenberg[5] recipe. The activity determinations by the mouse fall test showed the weak activity (ca. 4%) of the desoctapeptide insulin (C-terminus Arg B22). This activity increases drastically in three steps, when the amino acids Phe, Phe, Tyr (B24-26) are added successively to the insulin trunk. Coupling of Gly-Phe yields 14%, -Gly-Phe-Phe 36%, and -Gly-Phe-Phe-Tyr 61% of the biological activity (cryst. insulin=100%). The same peptides, elongated at their C-terminis with an alanyl residues (see above, series II) yield higher activities. Coupling these peptides to the arginyl residue B22 increases the activity as follows: -Gly-Phe-Ala, 36%, -Gly-Phe-Phe-Ala, 59%, and -Gly-Phe-Phe-Tyr-Ala, 91%. Comparing the activities of the variants with the C-termini-Gly-Phe-Phe (36%) and -Gly-Phe-Ala (36%) or -Gly-Phe-Phe-Tyr (61%) and -Gly-Phe-Phe-Ala (59%), it becomes clear that the aromatic amino acids Phe (B25) and Tyr (B26) can be substituted by Ala without loss of activity. In our preceding work (published 1969-1973 [3, 6-8]), we synthesized successively shortened insulin B-chains which yielded, after combination with natural A-chain, practically the same activity values as we have now obtained with the Ruttenberg semisynthesis. As we have already mentioned l.c.[1-4], it is obvious that the activity of insulin proceeds from the arginyl residue (B22) and is only intensified by the aromatic amino acids (B24-26). We[2,3] observed the same three-step increase in activity in the case of our synthetic oligopeptides Arg-Gly-Phe, Arg-Gly-Phe-Phe and Arg-Gly-Phe-Phe-Tyr (B22-26), which we assume to be the active region of insulin (1971[2]).", "contents": "Further studies on the three-step-increase in activity due to the aromatic amino acids B24-26 (-Phe-Phe-Tyr-). Using a reaction suite which was suggested by Ruttenberg [5] for the semisynthesis of insulin variants, insulin hexamethyl ester was digested by trypsin, then the N-terminal amino groups of the resulting desoctapeptide insulin pentamethyl ester were protected with the Boc residue. The free carboxyl group of the arginyl residue (B22) of this product was coupled to two different series of synthetic peptide methyl esters: I) Gly-OMe, Gly-Phe-OMe, Gly-Phe-Phe-OMe, Gly-Phe-Phe-Tyr-OMe and II) Gly-Ala-OMe, Gly-Phe-Ala-OMe, Gly-Phe-Phe-Ala-OMe, Gly-Phe-Phe-Tyr-Ala-OMe. Removal of all protecting groups yielded the corresponding insulin variants. The syntheses of these peptide methyl esters are described. Following the original prescription of Ruttenberg[5], we were not able to prepare the desired variants. That is why we were forced to change some important details of the Ruttenberg[5] recipe. The activity determinations by the mouse fall test showed the weak activity (ca. 4%) of the desoctapeptide insulin (C-terminus Arg B22). This activity increases drastically in three steps, when the amino acids Phe, Phe, Tyr (B24-26) are added successively to the insulin trunk. Coupling of Gly-Phe yields 14%, -Gly-Phe-Phe 36%, and -Gly-Phe-Phe-Tyr 61% of the biological activity (cryst. insulin=100%). The same peptides, elongated at their C-terminis with an alanyl residues (see above, series II) yield higher activities. Coupling these peptides to the arginyl residue B22 increases the activity as follows: -Gly-Phe-Ala, 36%, -Gly-Phe-Phe-Ala, 59%, and -Gly-Phe-Phe-Tyr-Ala, 91%. Comparing the activities of the variants with the C-termini-Gly-Phe-Phe (36%) and -Gly-Phe-Ala (36%) or -Gly-Phe-Phe-Tyr (61%) and -Gly-Phe-Phe-Ala (59%), it becomes clear that the aromatic amino acids Phe (B25) and Tyr (B26) can be substituted by Ala without loss of activity. In our preceding work (published 1969-1973 [3, 6-8]), we synthesized successively shortened insulin B-chains which yielded, after combination with natural A-chain, practically the same activity values as we have now obtained with the Ruttenberg semisynthesis. As we have already mentioned l.c.[1-4], it is obvious that the activity of insulin proceeds from the arginyl residue (B22) and is only intensified by the aromatic amino acids (B24-26). We[2,3] observed the same three-step increase in activity in the case of our synthetic oligopeptides Arg-Gly-Phe, Arg-Gly-Phe-Phe and Arg-Gly-Phe-Phe-Tyr (B22-26), which we assume to be the active region of insulin (1971[2])."} {"id": "PMID:1254247", "title": "Bile acid glucuronides, II[1]. Isolation and identification of a chenodeoxycholic acid glucuronide from human plasma in intrahepatic cholestasis.", "content": "The isolation of a glucurono-conjugate of a bile acid has been performed from human plasma in a case of chronic intrahepatic cholestasis. By means of a series of chromatographic steps, esterification with diazomethane and acetylation a mixture of methylester polyacetates of steroid glucuronides was obtained, which could be separated by thin-layer chromatography. Methyl 7alpha-acetoxy-3alpha-O-(methyl 2, 3, 4-tri-O-acetyl-beta-D-glucopyranosyluronate)5beta-cholan-24-oate, synthesized via the Koenigs-Knorr condensation reaction, was used as reference substance. From comparison of the chromatogrphic behaviour and the mass spectrum of the natural compound and the synthetic product the structure of the bile acid derivative isolated from plasma could be established as a peracetylated methylester of chenodeoxycholic acid-3-beta-D-glucuronide.", "contents": "Bile acid glucuronides, II[1]. Isolation and identification of a chenodeoxycholic acid glucuronide from human plasma in intrahepatic cholestasis. The isolation of a glucurono-conjugate of a bile acid has been performed from human plasma in a case of chronic intrahepatic cholestasis. By means of a series of chromatographic steps, esterification with diazomethane and acetylation a mixture of methylester polyacetates of steroid glucuronides was obtained, which could be separated by thin-layer chromatography. Methyl 7alpha-acetoxy-3alpha-O-(methyl 2, 3, 4-tri-O-acetyl-beta-D-glucopyranosyluronate)5beta-cholan-24-oate, synthesized via the Koenigs-Knorr condensation reaction, was used as reference substance. From comparison of the chromatogrphic behaviour and the mass spectrum of the natural compound and the synthetic product the structure of the bile acid derivative isolated from plasma could be established as a peracetylated methylester of chenodeoxycholic acid-3-beta-D-glucuronide."} {"id": "PMID:1254248", "title": "Bile acid glucuronides, III[1, 2]. Chemical synthesis and characterization of glucuronic acid coupled mono-, di- and trihydroxy bile acids.", "content": "The synthesis of bile acid-3-beta-D-monoglucuronides has been accomplished via the Koenigs-Knorr condensation reaction using methyl 2, 3, 4-tri-O-acetyl-1-deoxy-alpha-bromo-D-glucopyranuronate as coupling reagent. Chemical characteristics as melting points, elemental analyses, IR-spectra, isobutane-chemical ionization mass spectra and, in case of the derivative of 3alpha-hydroxy=5beta-cholanoate, NMR-spectra were recorded and can serve as a means of identification of these recently detected naturally occurring derivatives of bile acids in isolation procedures from biological sources.", "contents": "Bile acid glucuronides, III[1, 2]. Chemical synthesis and characterization of glucuronic acid coupled mono-, di- and trihydroxy bile acids. The synthesis of bile acid-3-beta-D-monoglucuronides has been accomplished via the Koenigs-Knorr condensation reaction using methyl 2, 3, 4-tri-O-acetyl-1-deoxy-alpha-bromo-D-glucopyranuronate as coupling reagent. Chemical characteristics as melting points, elemental analyses, IR-spectra, isobutane-chemical ionization mass spectra and, in case of the derivative of 3alpha-hydroxy=5beta-cholanoate, NMR-spectra were recorded and can serve as a means of identification of these recently detected naturally occurring derivatives of bile acids in isolation procedures from biological sources."} {"id": "PMID:1254249", "title": "Oxidative side reactions during dansylation of SH-compounds.", "content": "Dansyl chloride can act as an oxidizing agent on compounds which are easily oxidized. During the reaction of mercaptanes, e.g. cysteine, homocysteine, cysteamine, with dansyl chloride, the corresponding disulfides are formed and dansyl chloride is reduced to 5-dimethylaminonaphthalene 1-sulfinic acid. This reaction is so rapid that the normal dansylation can take place only after complete oxidation of all SH-compounds. Therefore only the dansyl derivatives of the corresponding disulfides are formed during normal dansylation of SH-compounds. If different SH-compounds are present in the reaction mixture mixed disulfides are formed as well. These can be separated by microchromatography on 3 X 3 cm micropolyamide sheets. Dependent on the concentration of dansyl chloride, 6 or even 15 different dansylated disulfides are formed from three different SH-compounds so that interpretation of these chromatograms is difficult. The actual dansylmercaptanes (e.g., dansylcysteine, dansylhomocysteine, dansylcysteamine) can be prepared by reduction of the dansylated disulfides with suitable reducing agents.", "contents": "Oxidative side reactions during dansylation of SH-compounds. Dansyl chloride can act as an oxidizing agent on compounds which are easily oxidized. During the reaction of mercaptanes, e.g. cysteine, homocysteine, cysteamine, with dansyl chloride, the corresponding disulfides are formed and dansyl chloride is reduced to 5-dimethylaminonaphthalene 1-sulfinic acid. This reaction is so rapid that the normal dansylation can take place only after complete oxidation of all SH-compounds. Therefore only the dansyl derivatives of the corresponding disulfides are formed during normal dansylation of SH-compounds. If different SH-compounds are present in the reaction mixture mixed disulfides are formed as well. These can be separated by microchromatography on 3 X 3 cm micropolyamide sheets. Dependent on the concentration of dansyl chloride, 6 or even 15 different dansylated disulfides are formed from three different SH-compounds so that interpretation of these chromatograms is difficult. The actual dansylmercaptanes (e.g., dansylcysteine, dansylhomocysteine, dansylcysteamine) can be prepared by reduction of the dansylated disulfides with suitable reducing agents."} {"id": "PMID:1254255", "title": "Expanding a sheltered workshop to replace nonpaying patient jobs.", "content": "Mental hospitals with large numbers of inactive chronic patients often have a history of hospital farms and shops that provided meaningful, though unpaid, occupation to hundreds of patients. The reforms of work programs brought about by the Souder v. Brennan decision were long overdue, the author says, but the resulting termination of work programs in many hospitals means many benefits to patients have been lost. At one state hospital, many of the jobs eliminated by the Souder decision were replaced by an expansion of the hospital's sheltered workshop, which operates under a work activities center certificate. A project in which patients made and assembled parts for unpainted wooden toys was responsible for much of the expansion.", "contents": "Expanding a sheltered workshop to replace nonpaying patient jobs. Mental hospitals with large numbers of inactive chronic patients often have a history of hospital farms and shops that provided meaningful, though unpaid, occupation to hundreds of patients. The reforms of work programs brought about by the Souder v. Brennan decision were long overdue, the author says, but the resulting termination of work programs in many hospitals means many benefits to patients have been lost. At one state hospital, many of the jobs eliminated by the Souder decision were replaced by an expansion of the hospital's sheltered workshop, which operates under a work activities center certificate. A project in which patients made and assembled parts for unpainted wooden toys was responsible for much of the expansion."} {"id": "PMID:1254316", "title": "[A comparison of two tests for rheumatoid factor: latex test and l-agglutination (author's transl)].", "content": "Positive and negative reactions of latex test (LX) and streptococcal L-agglutination (LA) were correlated significantly with one another. However, in approximately 70% of the sera tested only one test was positive, LX at a much higher rate than LA. Postive rheumatoid factor tests were found in 117 patients with rheumatoid arthritis and in 595 patients with other diseases, exclusive of connective tissue diseases. Among the seropositive patients with rheumatoid arthritis, a positive reaction was seen in 85% and 71% by LX or LA respectively. Patients with nonrheumatic diseases showed positive reactions at a rate of 3,1%, with 2,3% and 1,7% in LX or La respectively. This shows that LA is less sensitive, but more specific as compared with LX. With increasing age of the patients, the rate of \"nonspecific positive\" reactors in patients with nonrheumatic diseases increases, more strongly for LX than for LA. The distribution of positive tests (LX positive, LA positive, or both positive) was analyzed in various groups of patients. The rate of positive reactions in both tests is significantly higher than patients with rheumatoid arthritis; it further increases with the severity of the disease. In cases with positive CRP, the rate of sera positive in both tests is higher, equally in patients with and without rheumatoid arthritis. In patients with nonrheumatic diseases an elevated serum gamma-globulin is associated with positive reactions in both tests and with positive LX. In all other grouping of patients, the rheumatoid factor tests did not yield significant deviations from chance distribution, as determined by chi2 analysis.", "contents": "[A comparison of two tests for rheumatoid factor: latex test and l-agglutination (author's transl)]. Positive and negative reactions of latex test (LX) and streptococcal L-agglutination (LA) were correlated significantly with one another. However, in approximately 70% of the sera tested only one test was positive, LX at a much higher rate than LA. Postive rheumatoid factor tests were found in 117 patients with rheumatoid arthritis and in 595 patients with other diseases, exclusive of connective tissue diseases. Among the seropositive patients with rheumatoid arthritis, a positive reaction was seen in 85% and 71% by LX or LA respectively. Patients with nonrheumatic diseases showed positive reactions at a rate of 3,1%, with 2,3% and 1,7% in LX or La respectively. This shows that LA is less sensitive, but more specific as compared with LX. With increasing age of the patients, the rate of \"nonspecific positive\" reactors in patients with nonrheumatic diseases increases, more strongly for LX than for LA. The distribution of positive tests (LX positive, LA positive, or both positive) was analyzed in various groups of patients. The rate of positive reactions in both tests is significantly higher than patients with rheumatoid arthritis; it further increases with the severity of the disease. In cases with positive CRP, the rate of sera positive in both tests is higher, equally in patients with and without rheumatoid arthritis. In patients with nonrheumatic diseases an elevated serum gamma-globulin is associated with positive reactions in both tests and with positive LX. In all other grouping of patients, the rheumatoid factor tests did not yield significant deviations from chance distribution, as determined by chi2 analysis."} {"id": "PMID:1254317", "title": "[Detection of HBSAG in cerebrospinal fluid by means of a radioimmunoassay technique (author's transl)].", "content": "HBSAg was demonstrated radioimmunologically in cerebrospinal fluid in 7 out of 11 seropositive children with acute viral hepatitis B (1/2), fulminant viral hepatitis (0/1), chronic active hepatitis (2/4), chronic persistent hepatitis (1/1), cirrhosis (1/1), and asymptomatic carrier status (2/2). Counterelectrophoresis and complement fixation test lacked the necessary sensitivity to detect the antigen even in patients with high serum concentrations. The pass over of the cerebrospinal barrier appears to be dependent of the serum titer. Some neurologic symptoms in the early stage of acute viral hepatitis are probably connected with the appearance of HBSAg in cerebrospinal fluid. It is however unlikely that central-nervous-system dysfunctions observed in association with fulminant viral hepatitis and coma result from a direct effect of HBSAg or hepatitis B-virus. In chronic carriers the cerebrospinal fluid probably contains the antigen more frequent. The cerebrospinal fluid of HBSAg-positive patients has to be regarded as an infectious agent.", "contents": "[Detection of HBSAG in cerebrospinal fluid by means of a radioimmunoassay technique (author's transl)]. HBSAg was demonstrated radioimmunologically in cerebrospinal fluid in 7 out of 11 seropositive children with acute viral hepatitis B (1/2), fulminant viral hepatitis (0/1), chronic active hepatitis (2/4), chronic persistent hepatitis (1/1), cirrhosis (1/1), and asymptomatic carrier status (2/2). Counterelectrophoresis and complement fixation test lacked the necessary sensitivity to detect the antigen even in patients with high serum concentrations. The pass over of the cerebrospinal barrier appears to be dependent of the serum titer. Some neurologic symptoms in the early stage of acute viral hepatitis are probably connected with the appearance of HBSAg in cerebrospinal fluid. It is however unlikely that central-nervous-system dysfunctions observed in association with fulminant viral hepatitis and coma result from a direct effect of HBSAg or hepatitis B-virus. In chronic carriers the cerebrospinal fluid probably contains the antigen more frequent. The cerebrospinal fluid of HBSAg-positive patients has to be regarded as an infectious agent."} {"id": "PMID:1254319", "title": "Acquired resistance to ticks. I. Passive transfer of resistance.", "content": "Guinea-pigs developed resistance to larvae of the ixodid tick, Dermacentor andersoni, after one infestation. Resistance was characterized by guinea-pigs allowing fewer larvae to engorge (5-15%) during a second exposure than during an initial infestation (70-90%). Larvae feeding on resistant hosts weighed less than larvae engorging on a host with no previous exposure to ticks. Evidence is presented which indicates that this resistance can be passively transferred with viable lymph node cells, but not with serum, from resistant guinea-pigs. Recipients of cells from such resistant animals allowed significantly fewer larvae to engorge than did controls previously unexposed to ticks. This was not so in recipients of immune serum. The protection provided by passive transfer of cells from a resistant donor was not as complete as the protection afforded by natural exposure.", "contents": "Acquired resistance to ticks. I. Passive transfer of resistance. Guinea-pigs developed resistance to larvae of the ixodid tick, Dermacentor andersoni, after one infestation. Resistance was characterized by guinea-pigs allowing fewer larvae to engorge (5-15%) during a second exposure than during an initial infestation (70-90%). Larvae feeding on resistant hosts weighed less than larvae engorging on a host with no previous exposure to ticks. Evidence is presented which indicates that this resistance can be passively transferred with viable lymph node cells, but not with serum, from resistant guinea-pigs. Recipients of cells from such resistant animals allowed significantly fewer larvae to engorge than did controls previously unexposed to ticks. This was not so in recipients of immune serum. The protection provided by passive transfer of cells from a resistant donor was not as complete as the protection afforded by natural exposure."} {"id": "PMID:1254320", "title": "Cell-mediated cytotoxicity. Characterization of the effector cells.", "content": "Isolated human mononuclear cells were fractionated according to their membrane characteristics or physical properties. Adherent cells were depleted by filtration through glass columns; phagocytic cells were removed by iron treatment and cell subpopulations capable of forming rosettes with sheep erythrocytes (E), erythrocyte-antibody-complement (EAC) and chicken erythrocyte-antibody complexes (CEA) were separated by centrifugation of Ficoll-Hypaque gradients. The functional activity of the cell subpopulations obtained was assayed by testing PHA-induced cytoxicity (PIC), antibody-dependent cytoxicity (ADCC) and blast transformation by PHA. The results of this study demonstrate that: (1) cells reacting in PIC and ADCC assays are different, adherent and phagocytic cells being necessary for full expression of PIC and not for ADCC; (2) PHA induces direct blast transformation of purified E-RFC in the absence of PIC cytotoxic cells; (3) cell populations specifically enriched in E or EAC rosette-forming cells are not cytotoxic neither in the PHA nor in antibody mediated cytotoxic assays; (4) cells participating in ADCC can be selectively purified by centrifugation of CEA rosettes.", "contents": "Cell-mediated cytotoxicity. Characterization of the effector cells. Isolated human mononuclear cells were fractionated according to their membrane characteristics or physical properties. Adherent cells were depleted by filtration through glass columns; phagocytic cells were removed by iron treatment and cell subpopulations capable of forming rosettes with sheep erythrocytes (E), erythrocyte-antibody-complement (EAC) and chicken erythrocyte-antibody complexes (CEA) were separated by centrifugation of Ficoll-Hypaque gradients. The functional activity of the cell subpopulations obtained was assayed by testing PHA-induced cytoxicity (PIC), antibody-dependent cytoxicity (ADCC) and blast transformation by PHA. The results of this study demonstrate that: (1) cells reacting in PIC and ADCC assays are different, adherent and phagocytic cells being necessary for full expression of PIC and not for ADCC; (2) PHA induces direct blast transformation of purified E-RFC in the absence of PIC cytotoxic cells; (3) cell populations specifically enriched in E or EAC rosette-forming cells are not cytotoxic neither in the PHA nor in antibody mediated cytotoxic assays; (4) cells participating in ADCC can be selectively purified by centrifugation of CEA rosettes."} {"id": "PMID:1254321", "title": "Studies on lymph humoral factor. Evidence for a lymphocytopoietic factor in rat thoracic duct lymph.", "content": "Normal rats were injected with the partially purified material extracted from the thoracic duct lymph which was collected from normal syngeneic rats. The cellular changes in the peripheral lymphoid tissues and thymus were examined cytologically and histologically. The intravenous injection of the lymph extract into normal syngeneic rats resulted in increase in weight of lymphoid tissues. Histologically, a massive proliferation of large pyroninophilic lymphoid cells and an increase in mitotic index was detected predominantly in the thymus-dependent areas and thymic cortex. In spleens from rats injected with lymph extract, the marginal zone bridging channel was shown as one route for the translocation or mobilization of newly borne lymphoid cells to the venous circulation. Similar lymphocytopoietic activity, but to a lesser extent than lymph extract, was also detected in lymph plasma, serum and serum extract. The lymph extract was shown to be non-immunogenic in syngeneic rats. It is suggested that the effects of the lymph extract on lymphoid cell proliferation are due to the presence of a lymphocytopoietic factor in body fluid, particularly in the lymph.", "contents": "Studies on lymph humoral factor. Evidence for a lymphocytopoietic factor in rat thoracic duct lymph. Normal rats were injected with the partially purified material extracted from the thoracic duct lymph which was collected from normal syngeneic rats. The cellular changes in the peripheral lymphoid tissues and thymus were examined cytologically and histologically. The intravenous injection of the lymph extract into normal syngeneic rats resulted in increase in weight of lymphoid tissues. Histologically, a massive proliferation of large pyroninophilic lymphoid cells and an increase in mitotic index was detected predominantly in the thymus-dependent areas and thymic cortex. In spleens from rats injected with lymph extract, the marginal zone bridging channel was shown as one route for the translocation or mobilization of newly borne lymphoid cells to the venous circulation. Similar lymphocytopoietic activity, but to a lesser extent than lymph extract, was also detected in lymph plasma, serum and serum extract. The lymph extract was shown to be non-immunogenic in syngeneic rats. It is suggested that the effects of the lymph extract on lymphoid cell proliferation are due to the presence of a lymphocytopoietic factor in body fluid, particularly in the lymph."} {"id": "PMID:1254322", "title": "Evidence for the secretory transport mechanism of intestinal immunoglobulin. The ultrastructural distribution of IgM.", "content": "The intracellular localization of IgM in porcine intestinal tissue has been studied by immunoelectron microscopy and immunofluorescence. IgM was demonstrated in vesicles in the cytoplasm of crypt epithelial cells particularly in the supranuclear region. It was also shown in the ergastoplasmic cisternae of plasma cells in the intercryptal lamina propria. The findings are compared with those of a previous similar study on secretory IgA and their implications for possible mechanisms of selective transport are discussed.", "contents": "Evidence for the secretory transport mechanism of intestinal immunoglobulin. The ultrastructural distribution of IgM. The intracellular localization of IgM in porcine intestinal tissue has been studied by immunoelectron microscopy and immunofluorescence. IgM was demonstrated in vesicles in the cytoplasm of crypt epithelial cells particularly in the supranuclear region. It was also shown in the ergastoplasmic cisternae of plasma cells in the intercryptal lamina propria. The findings are compared with those of a previous similar study on secretory IgA and their implications for possible mechanisms of selective transport are discussed."} {"id": "PMID:1254323", "title": "[Nutrition physiological aspects in the treatment of obesity].", "content": "Obesity is one of the most common prosperity diseases. As a consequence of this disease there is a decrease in the expectation of life. Obesity is bascially caused by overeating. The low-caloric reducing diets are differentiated into a low-fat and high-carbohydrate form, and into a carbohydrate-free and high-fat diet. The metabolic advantages and the disadvantages of these two forms of low-caloric diets are discussed with respect to starvation metabolism. It is assumed that without ketoacidosis, at least 100-140 g glucose per day are required to meet the energetic demands of the central nervous system. Since the conversion rate of protein to glucose is about 2:1, during a carbohydrate-free diet about 200-260 g of protein per day would be necessary to meet the glucose requirements of the organism. As such a high-protein supply with food is almost impossible, ketogenesis in the liver must take place as a sort of \"glucose-sparing mechanism\". Only under these conditions, the otherwise extreme nitrogen catabolism can be avoided during an almost carbohydrate-free diet. However, using a fat-free (600 kcal) diet it is possible to furnish the glucose requirements of the central nervous system by the food supply. Therefore, a compensatory ketoacidosis is not required. Additionally, the fat-free diet does not contain cholesterol. In this way, the hypercholesterinemia which is a common feature in obesity is favourably influenced by the absence of foods of animal origin. Therefore, within a short period a marked decrease in serum cholesterol concentration results by the high-carbohydrate diet. The same is true for the concentration of free fatty acids and serum triglycerides. It is concluded that the high-carbohydrate low-caloric diet is suited best for reduction of body weight.", "contents": "[Nutrition physiological aspects in the treatment of obesity]. Obesity is one of the most common prosperity diseases. As a consequence of this disease there is a decrease in the expectation of life. Obesity is bascially caused by overeating. The low-caloric reducing diets are differentiated into a low-fat and high-carbohydrate form, and into a carbohydrate-free and high-fat diet. The metabolic advantages and the disadvantages of these two forms of low-caloric diets are discussed with respect to starvation metabolism. It is assumed that without ketoacidosis, at least 100-140 g glucose per day are required to meet the energetic demands of the central nervous system. Since the conversion rate of protein to glucose is about 2:1, during a carbohydrate-free diet about 200-260 g of protein per day would be necessary to meet the glucose requirements of the organism. As such a high-protein supply with food is almost impossible, ketogenesis in the liver must take place as a sort of \"glucose-sparing mechanism\". Only under these conditions, the otherwise extreme nitrogen catabolism can be avoided during an almost carbohydrate-free diet. However, using a fat-free (600 kcal) diet it is possible to furnish the glucose requirements of the central nervous system by the food supply. Therefore, a compensatory ketoacidosis is not required. Additionally, the fat-free diet does not contain cholesterol. In this way, the hypercholesterinemia which is a common feature in obesity is favourably influenced by the absence of foods of animal origin. Therefore, within a short period a marked decrease in serum cholesterol concentration results by the high-carbohydrate diet. The same is true for the concentration of free fatty acids and serum triglycerides. It is concluded that the high-carbohydrate low-caloric diet is suited best for reduction of body weight."} {"id": "PMID:1254324", "title": "[Problems of the intravenous access--a new instrument for the vena cava catheterization by way of the internal jugular vein].", "content": "Experience with a new Braunula is reported. However, even with this new punction set the long-term peripheral application of certain solutions is not possible. For this reason, more and more central-vein catheters must be used. Comparing the advantages and disadvantages of the subclavian catheter of the jugularis interna catheter the latter is preferred. A new set for this method is demonstrated.", "contents": "[Problems of the intravenous access--a new instrument for the vena cava catheterization by way of the internal jugular vein]. Experience with a new Braunula is reported. However, even with this new punction set the long-term peripheral application of certain solutions is not possible. For this reason, more and more central-vein catheters must be used. Comparing the advantages and disadvantages of the subclavian catheter of the jugularis interna catheter the latter is preferred. A new set for this method is demonstrated."} {"id": "PMID:1254325", "title": "[Microfilters and blood transfusion].", "content": "The use of microfilters for the transfusion of fresh blood and bank blood stored for 10 and 18 days is reported. No amorphous debris are found in the microfilter after perfusion of fresh blood. After perfusion of blood stored for 10 and 18 days, in two cases aggregates of platelets are found, amorphous debris, however, only in one case in the smallest mesh. On the other hand, in the 300 mu standard filter a passage of amorphous debris through the filter is often to be seen. It is possible that some manipulation has favoured this.", "contents": "[Microfilters and blood transfusion]. The use of microfilters for the transfusion of fresh blood and bank blood stored for 10 and 18 days is reported. No amorphous debris are found in the microfilter after perfusion of fresh blood. After perfusion of blood stored for 10 and 18 days, in two cases aggregates of platelets are found, amorphous debris, however, only in one case in the smallest mesh. On the other hand, in the 300 mu standard filter a passage of amorphous debris through the filter is often to be seen. It is possible that some manipulation has favoured this."} {"id": "PMID:1254326", "title": "[Nutritional problems in diseases of the small and large intestine].", "content": "18 patients with inflammatory bowel disease, among them ten with ulcerative colitis and 5 with Crohn's disease, were treated with the combined enteral-parenteral synthetic hypercaloric nutrition. By use of Vivasorb the clinical results were rather good. However, it was impossible to normalize the serumalbumin until the application of the formula diet BSD, enriched in amino acids. These experiences with BSD reveal much better results. All patients recovered nearly completely from their complaints and the clinical parameters went back to normal. Furthermore, it is easier to improve the flavour. The typical mode therapy is demonstrated on one patient with ulcerative colitis and one with Crohn's disease.", "contents": "[Nutritional problems in diseases of the small and large intestine]. 18 patients with inflammatory bowel disease, among them ten with ulcerative colitis and 5 with Crohn's disease, were treated with the combined enteral-parenteral synthetic hypercaloric nutrition. By use of Vivasorb the clinical results were rather good. However, it was impossible to normalize the serumalbumin until the application of the formula diet BSD, enriched in amino acids. These experiences with BSD reveal much better results. All patients recovered nearly completely from their complaints and the clinical parameters went back to normal. Furthermore, it is easier to improve the flavour. The typical mode therapy is demonstrated on one patient with ulcerative colitis and one with Crohn's disease."} {"id": "PMID:1254328", "title": "Central fractures of the acetabulum.", "content": "A series of 26 patients with central fractures of the acetabulum is presented with a follow-up of 3-13 years. Three patients had undisplaced fractures. In the remaining 23, long-term results of treatment by traction in 15 and by primary open reduction in 8 have been compared. A numerical grading system has been used for assessment. Results in the non-operative group were generally poor, only 2 being satisfactory. Some of the poorest scores in this group were associated with initial roof damage. Three patients required secondary salvage procedures because of severe pain and disability approximately 2 years after injury. Of the open reduction patients, all with roof damage, 4 had satisfactory results. Reasons for failure is the remaining 4 patients are discussed. Galloping degeneration due presumably to irreversible intra-articular cartilage damage at the initial injury, developed in 2 patients in the non-operative group and in one in the operative group.", "contents": "Central fractures of the acetabulum. A series of 26 patients with central fractures of the acetabulum is presented with a follow-up of 3-13 years. Three patients had undisplaced fractures. In the remaining 23, long-term results of treatment by traction in 15 and by primary open reduction in 8 have been compared. A numerical grading system has been used for assessment. Results in the non-operative group were generally poor, only 2 being satisfactory. Some of the poorest scores in this group were associated with initial roof damage. Three patients required secondary salvage procedures because of severe pain and disability approximately 2 years after injury. Of the open reduction patients, all with roof damage, 4 had satisfactory results. Reasons for failure is the remaining 4 patients are discussed. Galloping degeneration due presumably to irreversible intra-articular cartilage damage at the initial injury, developed in 2 patients in the non-operative group and in one in the operative group."} {"id": "PMID:1254329", "title": "Instances in which intramedullary nailing of a child's fracture is justifiable.", "content": "Two cases of fractures of the femur in childhood where internal fixation was indicated are described. Internal fixation of children's fractures is rarely justifiable (Blount, 1955), partly because of the rarity of non-union and partly because moulding usually corrects what may at first have been unacceptable deformity. Among the methods of internal fixation, K\u00fcntscher nailing for fracture of the shaft of a child's femur may seem to be the most difficult to defend. Nevertheless, there are occasions when it becomes necessary, although it might have been possible to avoid the operation by better care at the time.", "contents": "Instances in which intramedullary nailing of a child's fracture is justifiable. Two cases of fractures of the femur in childhood where internal fixation was indicated are described. Internal fixation of children's fractures is rarely justifiable (Blount, 1955), partly because of the rarity of non-union and partly because moulding usually corrects what may at first have been unacceptable deformity. Among the methods of internal fixation, K\u00fcntscher nailing for fracture of the shaft of a child's femur may seem to be the most difficult to defend. Nevertheless, there are occasions when it becomes necessary, although it might have been possible to avoid the operation by better care at the time."} {"id": "PMID:1254330", "title": "A report of 3 cases of simultaneous Colles' and scaphoid fractures.", "content": "Three cases of simultaneous Colles' and scaphoid fractures, one bilateral, occurring in a series of 422 Colles' fractures are presented. The factors necessary for the occurrence of such injuries are discussed.", "contents": "A report of 3 cases of simultaneous Colles' and scaphoid fractures. Three cases of simultaneous Colles' and scaphoid fractures, one bilateral, occurring in a series of 422 Colles' fractures are presented. The factors necessary for the occurrence of such injuries are discussed."} {"id": "PMID:1254331", "title": "Complications of fractures of the clavicle.", "content": "Most fractures of the clavicle unite without incident. The number and diversity of the methods of treatment in use suggest that in most cases good results are obtained despite medical supervision. Yet occasionally complications do arise. This paper describes two such cases and reviews the literature in search of a common factor to account for these complications. Cases presenting with early and late complications of fractures of the clavicle are described and the literature on the subject reviewed. The incidence of complications is highest in cases of direct violence to the shoulder region producing comminuted fractures. Surgical management is outlined in general terms. It is suggested that more prolonged and rigorous immobilization of cases \"at risk\" may reduce the incidence of non-union and prevent late neurovascular complications.", "contents": "Complications of fractures of the clavicle. Most fractures of the clavicle unite without incident. The number and diversity of the methods of treatment in use suggest that in most cases good results are obtained despite medical supervision. Yet occasionally complications do arise. This paper describes two such cases and reviews the literature in search of a common factor to account for these complications. Cases presenting with early and late complications of fractures of the clavicle are described and the literature on the subject reviewed. The incidence of complications is highest in cases of direct violence to the shoulder region producing comminuted fractures. Surgical management is outlined in general terms. It is suggested that more prolonged and rigorous immobilization of cases \"at risk\" may reduce the incidence of non-union and prevent late neurovascular complications."} {"id": "PMID:1254332", "title": "The use of plaster casts in the treatment of fractures of the femoral shaft.", "content": "In order to relieve the pressure on an overworked fracture service, the early mobilization of patients with fractures of the femoral shaft in plaster casts was investigated. The cast is designed to have a weight-relieving function and to mould the soft tissues of the thigh around the fracture. Using this method, 40 patients were discharged from hospital in an average of 44 days from injury and all their fractures healed rapidly and successfully.", "contents": "The use of plaster casts in the treatment of fractures of the femoral shaft. In order to relieve the pressure on an overworked fracture service, the early mobilization of patients with fractures of the femoral shaft in plaster casts was investigated. The cast is designed to have a weight-relieving function and to mould the soft tissues of the thigh around the fracture. Using this method, 40 patients were discharged from hospital in an average of 44 days from injury and all their fractures healed rapidly and successfully."} {"id": "PMID:1254333", "title": "Tardy palsy of the radial nerve from a Monteggia fracture.", "content": "A case of tardy palsy of the radial nerve, which developed 65 years after a Monteggia fracture that remained unreduced, is described. The weakness recovered sufficiently well for a tendon transference to bu unnecessary, partly because the patient was semi-retired. This condition is rare but comparison with the only two similar reported case of tardy radial and posterior interosseous nerve palsy associated with long-standing dislocation of the superior radio-ulnar joint suggests that the prognosis for recovery of such a palsy following excision of the radial head is better than might be expected.", "contents": "Tardy palsy of the radial nerve from a Monteggia fracture. A case of tardy palsy of the radial nerve, which developed 65 years after a Monteggia fracture that remained unreduced, is described. The weakness recovered sufficiently well for a tendon transference to bu unnecessary, partly because the patient was semi-retired. This condition is rare but comparison with the only two similar reported case of tardy radial and posterior interosseous nerve palsy associated with long-standing dislocation of the superior radio-ulnar joint suggests that the prognosis for recovery of such a palsy following excision of the radial head is better than might be expected."} {"id": "PMID:1254334", "title": "Intra-articular fractures of the calcaneum.", "content": "A method of reducing deformity of displaced, intra-articular fractures of the calcaneum is described, together with a programme of management aimed at restoring a painless and mobile foot. The clinical and radiographic results are presented in 41 patients treated over a 10-year-period, with a minimum follow-up of 2 years. The complications, none of which were serious, are described. The results are compared with a group of 52 patients whose fractures were treated over the same period by early movements without any attempt at reduction. Although disabling pain was not a notable feature in either group, more patients in the reduced group had resumed work of a heavy nature entailing climbing or walking on rough ground. Analysis of the figures suggests that this is related to the better function regained in the subtalar joint by this group.", "contents": "Intra-articular fractures of the calcaneum. A method of reducing deformity of displaced, intra-articular fractures of the calcaneum is described, together with a programme of management aimed at restoring a painless and mobile foot. The clinical and radiographic results are presented in 41 patients treated over a 10-year-period, with a minimum follow-up of 2 years. The complications, none of which were serious, are described. The results are compared with a group of 52 patients whose fractures were treated over the same period by early movements without any attempt at reduction. Although disabling pain was not a notable feature in either group, more patients in the reduced group had resumed work of a heavy nature entailing climbing or walking on rough ground. Analysis of the figures suggests that this is related to the better function regained in the subtalar joint by this group."} {"id": "PMID:1254336", "title": "Recurrent severe haemorrhage from false aneurysm following fracture of the femur.", "content": "A case of traumatic false aneurysm presenting as recurrent exsanguinating haemorrhage from a surgical wound of the thigh is described. A plate, inserted to maintain reduction of a fracture of the femur, was removed during the third attempt to control the bleeding and only then was the source revealed. Diagnostic difficulty delayed definitive treatment.", "contents": "Recurrent severe haemorrhage from false aneurysm following fracture of the femur. A case of traumatic false aneurysm presenting as recurrent exsanguinating haemorrhage from a surgical wound of the thigh is described. A plate, inserted to maintain reduction of a fracture of the femur, was removed during the third attempt to control the bleeding and only then was the source revealed. Diagnostic difficulty delayed definitive treatment."} {"id": "PMID:1254337", "title": "Major venous injuries and bullet wounds.", "content": "A review of the reported incidence, management and results of treatment of major vein injuries is presented and a brief account given of the mechanism of vascular damage by high-velocity bullet wounds. This paper reports 3 cases of isolated major venous injury caused by high-velocity bullets. Repair was performed in each case. Two patients survived with a good short-term clinical result. The third patient died during operation. The advantages of repairing injured veins are discussed.", "contents": "Major venous injuries and bullet wounds. A review of the reported incidence, management and results of treatment of major vein injuries is presented and a brief account given of the mechanism of vascular damage by high-velocity bullet wounds. This paper reports 3 cases of isolated major venous injury caused by high-velocity bullets. Repair was performed in each case. Two patients survived with a good short-term clinical result. The third patient died during operation. The advantages of repairing injured veins are discussed."} {"id": "PMID:1254339", "title": "A comparison of deaths from injury. 1947-56 compared with 1962-71.", "content": "Deaths from injury occurring during a recent 10-year period at the Birmingham Accident Hospital were compared with those occurring during a similar period 15 years earlier. Reliable comparisons were not possible because of changes in policy that tended to reduce the delay in getting badly injured persons to hospital. The figures did show: 1. A slight increase in the number of deaths from domestic accidents which might account for: 2. A slight increase in the number of deaths following fracture of the femur. 3. A slight decrease in the number of deaths from road accidents. 4. A slight decrease in the number of deaths following head injury and a tendency for these deaths to be delayed in the second 10-year period. 5. Deaths following injuries of the trunk were mostly due to bleeding and some of these could be looked on as examples of failure in diagnosis or resuscitation or both. What still remains true is that prompt diagnosis and resuscitation, and well-judged definitive treatment offer the best prospect of reducing mortality. Accurate diagnosis may owe much to technical aids but it also requires observation of physical signs in the light of well-known patterns of injury.", "contents": "A comparison of deaths from injury. 1947-56 compared with 1962-71. Deaths from injury occurring during a recent 10-year period at the Birmingham Accident Hospital were compared with those occurring during a similar period 15 years earlier. Reliable comparisons were not possible because of changes in policy that tended to reduce the delay in getting badly injured persons to hospital. The figures did show: 1. A slight increase in the number of deaths from domestic accidents which might account for: 2. A slight increase in the number of deaths following fracture of the femur. 3. A slight decrease in the number of deaths from road accidents. 4. A slight decrease in the number of deaths following head injury and a tendency for these deaths to be delayed in the second 10-year period. 5. Deaths following injuries of the trunk were mostly due to bleeding and some of these could be looked on as examples of failure in diagnosis or resuscitation or both. What still remains true is that prompt diagnosis and resuscitation, and well-judged definitive treatment offer the best prospect of reducing mortality. Accurate diagnosis may owe much to technical aids but it also requires observation of physical signs in the light of well-known patterns of injury."} {"id": "PMID:1254349", "title": "A computer program to derive the rate equations of enzyme catalysed reactions with up to ten enzyme-containing intermediates in the reaction mechanism.", "content": "The paper describes a program, designed for a desk-top computer, which can be used to derive the rate equations of enzyme catalysed reactions with up to ten enzyme-containing intermediates included in the mechanism. The program allows the rate equation to be presented in simplified forms of practical use and in a variety of formats.", "contents": "A computer program to derive the rate equations of enzyme catalysed reactions with up to ten enzyme-containing intermediates in the reaction mechanism. The paper describes a program, designed for a desk-top computer, which can be used to derive the rate equations of enzyme catalysed reactions with up to ten enzyme-containing intermediates included in the mechanism. The program allows the rate equation to be presented in simplified forms of practical use and in a variety of formats."} {"id": "PMID:1254350", "title": "A systems model of blood glucose control.", "content": "A mathematical model for the short-term control of glucose is presented, focusing upon the role of the liver. Non-linear representation is provided, enabling complete system behaviour of the metabolic and endocrine processes to be analysed, including both basic auto-regulation and higher levels of control. The level of a priori knowledge incorporated in the formulation is maximised by including unit process dynamics, making direct use of known enzymological data. From simulation results, hypotheses concerning system structure are tested. Hormones are seen to be important in maintaining the biochemical environment, providing the coarse control. The dominant control of flux within the glucose metabolic pathways is intrinsic to the enzyme systems which can be looked upon as providing the fine tuning and auto regulatory effects.", "contents": "A systems model of blood glucose control. A mathematical model for the short-term control of glucose is presented, focusing upon the role of the liver. Non-linear representation is provided, enabling complete system behaviour of the metabolic and endocrine processes to be analysed, including both basic auto-regulation and higher levels of control. The level of a priori knowledge incorporated in the formulation is maximised by including unit process dynamics, making direct use of known enzymological data. From simulation results, hypotheses concerning system structure are tested. Hormones are seen to be important in maintaining the biochemical environment, providing the coarse control. The dominant control of flux within the glucose metabolic pathways is intrinsic to the enzyme systems which can be looked upon as providing the fine tuning and auto regulatory effects."} {"id": "PMID:1254351", "title": "Some aspects of a stochastic two locus selfing genetic model with selection and computer simulation.", "content": "The present paper examines a specific genetic model as a finite Markov process, using the normal matrix approach. This model is the two locus selfing model with selection studied by Tan (1973), who used an eigenvalue approach. The properties of the process are analytically and numerically investigated and the effects of selection and cross-over on the transition from a heterozygotic parent through several generations of heterozygotic progeny are assessed. These results enlarge upon Tan's work and, in addition, present two new aspects of the model. In particular (1) the expected number of generations of heterozygotic progeny of genotype j that will descend from a heterozygotic parent of genotype i and (2) the variance of this number of generations about the mean value have not been previously considered.", "contents": "Some aspects of a stochastic two locus selfing genetic model with selection and computer simulation. The present paper examines a specific genetic model as a finite Markov process, using the normal matrix approach. This model is the two locus selfing model with selection studied by Tan (1973), who used an eigenvalue approach. The properties of the process are analytically and numerically investigated and the effects of selection and cross-over on the transition from a heterozygotic parent through several generations of heterozygotic progeny are assessed. These results enlarge upon Tan's work and, in addition, present two new aspects of the model. In particular (1) the expected number of generations of heterozygotic progeny of genotype j that will descend from a heterozygotic parent of genotype i and (2) the variance of this number of generations about the mean value have not been previously considered."} {"id": "PMID:1254353", "title": "Temperature-sensitive DNA repair of ultraviolet damage in human cell lines.", "content": "Following exposure to ultraviolet irradiation (UV), two of three human fibroblast strains and one of three melanoma cell lines showed lower rates of thymine dimer excision during 24 h at 40 degrees C than at 36 degrees C. All lines had lower rates at 32 degrees C. Autoradiographic studies of three fibroblast strains and four melanoma lines incubated for four hours after irradiation revealed decreased unscheduled DNA synthesis at 42 degrees C compared with 36 degrees C. The rate of semiconservative DNA synthesis was decreased at the upper temperature in both series of experiments. All eight cell lines tested showed decreased repair at 42 degrees C, as judged by slower sedimentation and increased heterogeneity of parental DNA in alkaline sucrose gradients. Experiments using the DNA synthesis inhibitor Actinomycin D suggested that these effects were due to temperature-sensitive repair synthesis. In the two lines studied, preincubation of cells at 42 degrees C apparently increased the extent of UV damage. Although by no means conclusive, these results are consistent with the possibility that temperature-sensitive DNA repair is a contributory factor in some cases of solar carcinogenesis.", "contents": "Temperature-sensitive DNA repair of ultraviolet damage in human cell lines. Following exposure to ultraviolet irradiation (UV), two of three human fibroblast strains and one of three melanoma cell lines showed lower rates of thymine dimer excision during 24 h at 40 degrees C than at 36 degrees C. All lines had lower rates at 32 degrees C. Autoradiographic studies of three fibroblast strains and four melanoma lines incubated for four hours after irradiation revealed decreased unscheduled DNA synthesis at 42 degrees C compared with 36 degrees C. The rate of semiconservative DNA synthesis was decreased at the upper temperature in both series of experiments. All eight cell lines tested showed decreased repair at 42 degrees C, as judged by slower sedimentation and increased heterogeneity of parental DNA in alkaline sucrose gradients. Experiments using the DNA synthesis inhibitor Actinomycin D suggested that these effects were due to temperature-sensitive repair synthesis. In the two lines studied, preincubation of cells at 42 degrees C apparently increased the extent of UV damage. Although by no means conclusive, these results are consistent with the possibility that temperature-sensitive DNA repair is a contributory factor in some cases of solar carcinogenesis."} {"id": "PMID:1254354", "title": "Incidence rates of specific histological types of lung cancer in Singapore Chinese dialect groups, and their aetiological significance.", "content": "Significant differences in the incidence levels of lung cancer have been observed among major Chinese dialect groups or communities (Kokkien, Teochew and Cantonese) in Singapore. Among males, the incidence rate is highest in the Hokkiens (age-standardized incidence rate per 100,000 persons per year in Hokkien 67.8, Teochew 55.3, Cantonese 54.0) and among females, it is highest in the Cantonese (Hokkien 12.4, Teochew 12.8, Cantonese 27.2). The present investigation was undertaken to determine the incidence rates of each of the main histological types of lung cancer in the Chinese population and to determine whether there are any correlations between histological patterns and the dialect group differentials that may be of aetiological significance. During the period 1968-1972, a total of 1,747 cases of lung cancer (1,285 males and 462 females) were reported to the Singapore Cancer Registry. It proved possible to type the neoplasms histologically in 476 males (37.0%) and 154 females (33.3%). Age-standardized rates by histological type were computed on the assumption that those histologically typed were a representative sample of all lung cancers. This study shows that Hokkien males have a significantly higher incidence rate of epidermoid carcinoma than the other dialect groups (Hokkien 36.1, Teochew 21.1, Cantonese 17.3). The Cantonese females have significantly higher incidence rates of both epidermoid carcinoma (Hokkien 3.7, Teochew 2.3, Cantonese 5.9) and adenocarcinoma (Hokkien 4.6, Teochew 3.6, Cantonese 11.9). Various sources of bias in studied of this type were examined; it is concluded that the differences in the histologic-specific incidence rates of lung cancer among the various Chinese dialect groups in Singapore are real and not artefactual. The significance of these findings in relation to possible aetiological factors is discussed.", "contents": "Incidence rates of specific histological types of lung cancer in Singapore Chinese dialect groups, and their aetiological significance. Significant differences in the incidence levels of lung cancer have been observed among major Chinese dialect groups or communities (Kokkien, Teochew and Cantonese) in Singapore. Among males, the incidence rate is highest in the Hokkiens (age-standardized incidence rate per 100,000 persons per year in Hokkien 67.8, Teochew 55.3, Cantonese 54.0) and among females, it is highest in the Cantonese (Hokkien 12.4, Teochew 12.8, Cantonese 27.2). The present investigation was undertaken to determine the incidence rates of each of the main histological types of lung cancer in the Chinese population and to determine whether there are any correlations between histological patterns and the dialect group differentials that may be of aetiological significance. During the period 1968-1972, a total of 1,747 cases of lung cancer (1,285 males and 462 females) were reported to the Singapore Cancer Registry. It proved possible to type the neoplasms histologically in 476 males (37.0%) and 154 females (33.3%). Age-standardized rates by histological type were computed on the assumption that those histologically typed were a representative sample of all lung cancers. This study shows that Hokkien males have a significantly higher incidence rate of epidermoid carcinoma than the other dialect groups (Hokkien 36.1, Teochew 21.1, Cantonese 17.3). The Cantonese females have significantly higher incidence rates of both epidermoid carcinoma (Hokkien 3.7, Teochew 2.3, Cantonese 5.9) and adenocarcinoma (Hokkien 4.6, Teochew 3.6, Cantonese 11.9). Various sources of bias in studied of this type were examined; it is concluded that the differences in the histologic-specific incidence rates of lung cancer among the various Chinese dialect groups in Singapore are real and not artefactual. The significance of these findings in relation to possible aetiological factors is discussed."} {"id": "PMID:1254355", "title": "A cohort study on mortality from cancer and other causes among workers at a metal refinery.", "content": "A non-concurrent prospective study was made on deaths from cancer and other causes occurring among 2,675 male workers at a metal refinery from 1949 to 1971. The expected number of deaths computed by applying age- and cause-specific death rates of Japanese males to these workers was compared with the observed number of deaths. Among 839 copper smelters, significantly increased mortalities were noted for lung cancer (SMR = 1,189) and colon cancer, but nor for cancer of the stomach, liver (primary) and biliary passages, pancreas and skin or for leukemia, tuberculosis, cerebrovascular diseases, heart diseases and liver cirrhosis. A dose-response relationship was demonstrated between the mortality from lung cancer and the degree of exposure. A very high excess mortality from lung cancer (SMR = 2,500) was seen among copper smelters who were considered to have been most heavily exposed to arsenic or workers who had engaged in sintering and blast furnace operations for 15 years of more before 1949. The latent period of lung cancer was 37.6 years on average, and not related to level of exposure. Twenty-six of 29 deaths from lung cancer among copper smelters occurred after they had left the refinery. Other production workers and clerical workers showed no significant excess mortality from any kind of cancer.", "contents": "A cohort study on mortality from cancer and other causes among workers at a metal refinery. A non-concurrent prospective study was made on deaths from cancer and other causes occurring among 2,675 male workers at a metal refinery from 1949 to 1971. The expected number of deaths computed by applying age- and cause-specific death rates of Japanese males to these workers was compared with the observed number of deaths. Among 839 copper smelters, significantly increased mortalities were noted for lung cancer (SMR = 1,189) and colon cancer, but nor for cancer of the stomach, liver (primary) and biliary passages, pancreas and skin or for leukemia, tuberculosis, cerebrovascular diseases, heart diseases and liver cirrhosis. A dose-response relationship was demonstrated between the mortality from lung cancer and the degree of exposure. A very high excess mortality from lung cancer (SMR = 2,500) was seen among copper smelters who were considered to have been most heavily exposed to arsenic or workers who had engaged in sintering and blast furnace operations for 15 years of more before 1949. The latent period of lung cancer was 37.6 years on average, and not related to level of exposure. Twenty-six of 29 deaths from lung cancer among copper smelters occurred after they had left the refinery. Other production workers and clerical workers showed no significant excess mortality from any kind of cancer."} {"id": "PMID:1254356", "title": "Capillary tube leukocyte adherence inhibition: an assay for cell-mediated immunity in cancer patients.", "content": "The leukocyte adherence inhibition (LAI) assay has been modified and automated in order to facilitate its clinical application. This new assay-the capillary tube LAI test-correlated with delayed cutaneous hypersensitivity using streptokinase-streptodornase antigen in 83% of the cases. When tested with a 3 M KC1 lung carcinoma antigen, lung carcinoma patients' leukocytes were more frequently inhibited (55%) than those of controls (normals 6%, other tumors 20%).", "contents": "Capillary tube leukocyte adherence inhibition: an assay for cell-mediated immunity in cancer patients. The leukocyte adherence inhibition (LAI) assay has been modified and automated in order to facilitate its clinical application. This new assay-the capillary tube LAI test-correlated with delayed cutaneous hypersensitivity using streptokinase-streptodornase antigen in 83% of the cases. When tested with a 3 M KC1 lung carcinoma antigen, lung carcinoma patients' leukocytes were more frequently inhibited (55%) than those of controls (normals 6%, other tumors 20%)."} {"id": "PMID:1254357", "title": "Studies on a gross-virus-induced lymphoma in the rat. III. Optimisation, specificity and applications of the in vitro immune response.", "content": "Conditions are described for optimal stimulation in vitro of lymphocytes from rats primed in vivo with syngeneic MuLV-G leukaemia cells. Cultures generate effector cells which show high cytotoxic activity against leukaemic cells. Specific stimulation can be obtained with leukaemic cells and with disrupted MuLV. Leukaemic cells, normal spleen cells and the viron internal protein p30 competitively inhibit effector cells, but purified virus exerts non-specific inhibition. These findings are interpreted as supporting the hypothesis that virion antigens constitute a major target of anti-tumour cytotoxic immunity.", "contents": "Studies on a gross-virus-induced lymphoma in the rat. III. Optimisation, specificity and applications of the in vitro immune response. Conditions are described for optimal stimulation in vitro of lymphocytes from rats primed in vivo with syngeneic MuLV-G leukaemia cells. Cultures generate effector cells which show high cytotoxic activity against leukaemic cells. Specific stimulation can be obtained with leukaemic cells and with disrupted MuLV. Leukaemic cells, normal spleen cells and the viron internal protein p30 competitively inhibit effector cells, but purified virus exerts non-specific inhibition. These findings are interpreted as supporting the hypothesis that virion antigens constitute a major target of anti-tumour cytotoxic immunity."} {"id": "PMID:1254358", "title": "The influence of vitamin A on the susceptibility of the rat lung to 3-methylcholanthrene.", "content": "The susceptibility of rats to pulmonary carcinogens is increased in the absence of vitamin A intake even when considerable amounts (0.4 nmole/mg) of vitamin A are stored in the liver and deficiency symptoms are absent. This was demonstrated in studies on the induction of metaplastic lung nodules by intratracheally administered 3-methylcholanthrene. Only moderate amounts of all-trans-retinyl acetate in the diet (7.6 nmole/g of diet) were required to prevent the development of this state of enhanced susceptibility. A further increase in intake of retinoids (by intragastric administration of either all-trans-retinyl acetate or 13-cis-retinoic acid) provided no additional protection against the effects of carcinogen.", "contents": "The influence of vitamin A on the susceptibility of the rat lung to 3-methylcholanthrene. The susceptibility of rats to pulmonary carcinogens is increased in the absence of vitamin A intake even when considerable amounts (0.4 nmole/mg) of vitamin A are stored in the liver and deficiency symptoms are absent. This was demonstrated in studies on the induction of metaplastic lung nodules by intratracheally administered 3-methylcholanthrene. Only moderate amounts of all-trans-retinyl acetate in the diet (7.6 nmole/g of diet) were required to prevent the development of this state of enhanced susceptibility. A further increase in intake of retinoids (by intragastric administration of either all-trans-retinyl acetate or 13-cis-retinoic acid) provided no additional protection against the effects of carcinogen."} {"id": "PMID:1254359", "title": "Monkey antisera with increased specificity to carcino-embryonic antigen (CEA).", "content": "Three Macaca irus monkeys were immunized with purified human CEA. One received unmodified CEA and two were immunized with haptenated (4-hydroxy-5-iodo-3-nitrophenyl acetyl) CEA. All three monkeys formed precipitating antibodies to CEA. The antisera did not precipitate the CEA-related normal glycoprotein antigen (NCA). In contrast, CEA-immunized rabbits, sheep and goats invariably form antibodies against NCA. Radio-immunoassays showed the monkey antisera to contain trace amounts of antibodies to NCA but the titers were about 10-1,000 times lower than those in rabbit and sheep sera with comparable anti-CEA titers. These results show that monkeys produce antibodies against CEA, but respond weakly to a normal, CEA-related antigen. The weak response to NCA suggests that monkeys may possess an NCA-related antigen. Antisera lacking reactivity to normal CEA-related antigens may be helpful in establishing a more specific diagnostic test for CEA.", "contents": "Monkey antisera with increased specificity to carcino-embryonic antigen (CEA). Three Macaca irus monkeys were immunized with purified human CEA. One received unmodified CEA and two were immunized with haptenated (4-hydroxy-5-iodo-3-nitrophenyl acetyl) CEA. All three monkeys formed precipitating antibodies to CEA. The antisera did not precipitate the CEA-related normal glycoprotein antigen (NCA). In contrast, CEA-immunized rabbits, sheep and goats invariably form antibodies against NCA. Radio-immunoassays showed the monkey antisera to contain trace amounts of antibodies to NCA but the titers were about 10-1,000 times lower than those in rabbit and sheep sera with comparable anti-CEA titers. These results show that monkeys produce antibodies against CEA, but respond weakly to a normal, CEA-related antigen. The weak response to NCA suggests that monkeys may possess an NCA-related antigen. Antisera lacking reactivity to normal CEA-related antigens may be helpful in establishing a more specific diagnostic test for CEA."} {"id": "PMID:1254360", "title": "Mixed lymphocyte/tumor-cell interaction in a murine sarcoma virus (Moloney)-induced tumor system. Comparison between lymphoproliferation and lymphocyte cytotoxicity.", "content": "Studies of the MLTI were performed in a primary MSV-induced tumor system. Reactivity against mitomycin-C-treated RBL-5 cells could be detected during a limited period at about 14 days after virus injection. The degree of reactivity of MSV 14 spleen cells was quite variable; stimulation indices ranged from 2.2 to 9.4. Activity in the MLTI appeared to a great extent to be dependent on T-lymphocytes. A relatively broad spectrum of specificity was demonstrated in experiments using additional stimulating cells besides RBL-5. The kinetics of the MLTI correlated well with the kinetics of the primary cytotoxic response in the CRA against RBL-5 cells. However, positive results in the in vivo and in vitro secondary cytotoxicity assays could be detected between 21 and 100 days after MSV injection when the MLTI was negative. Transplantation resistance against challenge with RBL-5 tumor cells also persists for a long time after MSV inoculation. Our data therefore indicate that the MLTI, in contrast to the secondary cytotoxicity assays, does not correlate well with the status of in vivo immunity.", "contents": "Mixed lymphocyte/tumor-cell interaction in a murine sarcoma virus (Moloney)-induced tumor system. Comparison between lymphoproliferation and lymphocyte cytotoxicity. Studies of the MLTI were performed in a primary MSV-induced tumor system. Reactivity against mitomycin-C-treated RBL-5 cells could be detected during a limited period at about 14 days after virus injection. The degree of reactivity of MSV 14 spleen cells was quite variable; stimulation indices ranged from 2.2 to 9.4. Activity in the MLTI appeared to a great extent to be dependent on T-lymphocytes. A relatively broad spectrum of specificity was demonstrated in experiments using additional stimulating cells besides RBL-5. The kinetics of the MLTI correlated well with the kinetics of the primary cytotoxic response in the CRA against RBL-5 cells. However, positive results in the in vivo and in vitro secondary cytotoxicity assays could be detected between 21 and 100 days after MSV injection when the MLTI was negative. Transplantation resistance against challenge with RBL-5 tumor cells also persists for a long time after MSV inoculation. Our data therefore indicate that the MLTI, in contrast to the secondary cytotoxicity assays, does not correlate well with the status of in vivo immunity."} {"id": "PMID:1254361", "title": "Alteration of the cell membrane architecture during suspension and monolayer culturing.", "content": "Using suspension-growth-adapted HeLa (S3) cells, we followed the alterations in cell morphology during attachment and spreading on a glass surface in vitro by scanning electron microscopy. Suspension cultivation obviated the need for trypsinization or EDTA treatment of the cells before seeding, thus the cell surface was not chemically altered. The suspension-grown cells were sperical and covered with microvilli. Three hours after seeding into stationary culture, attached cells had surface blebs and large processes, but no microvilli. During the following 9 h, the surface topography altered stepwise producing a complex lamelloplasm. The paper discusses how these membrane events are related to the cell cycle and metastasis.", "contents": "Alteration of the cell membrane architecture during suspension and monolayer culturing. Using suspension-growth-adapted HeLa (S3) cells, we followed the alterations in cell morphology during attachment and spreading on a glass surface in vitro by scanning electron microscopy. Suspension cultivation obviated the need for trypsinization or EDTA treatment of the cells before seeding, thus the cell surface was not chemically altered. The suspension-grown cells were sperical and covered with microvilli. Three hours after seeding into stationary culture, attached cells had surface blebs and large processes, but no microvilli. During the following 9 h, the surface topography altered stepwise producing a complex lamelloplasm. The paper discusses how these membrane events are related to the cell cycle and metastasis."} {"id": "PMID:1254362", "title": "Graduates and splitees from therapeutic community drug treatment programs: a comparison.", "content": "As greater numbers of drug abusers seek treatment and drug rehabilitation program resources become more and more scarce, selection processes should become based on scientific research rather than on the intuition of a few influential personnel. Many therapeutic community drug treatment programs have a preferential policy for accepting voluntary over court-ordered commitments. Our findings indicate that such a policy discriminates against those individuals who are most likely to succeed in completing their treatment. Our data also indicate that the success of male drug addicts in completing therapeutic community drug treatment programs is associated with sociological variables. The success of women, on the other hand, is more associated with psychologically oriented concerns.", "contents": "Graduates and splitees from therapeutic community drug treatment programs: a comparison. As greater numbers of drug abusers seek treatment and drug rehabilitation program resources become more and more scarce, selection processes should become based on scientific research rather than on the intuition of a few influential personnel. Many therapeutic community drug treatment programs have a preferential policy for accepting voluntary over court-ordered commitments. Our findings indicate that such a policy discriminates against those individuals who are most likely to succeed in completing their treatment. Our data also indicate that the success of male drug addicts in completing therapeutic community drug treatment programs is associated with sociological variables. The success of women, on the other hand, is more associated with psychologically oriented concerns."} {"id": "PMID:1254363", "title": "Interpersonal relationships in heroin use by men and women and their role in treatment outcome.", "content": "The majority of both male and female heroin addicts entering a city treatment program were introduced to heroin by a male. But by contrast with the males, females were in many cases introduced to heroin by another woman, more often used drugs with persons of both sexes, and were more likely to be living with a current or former heroin user at intake. Encouragement to give up drugs was reported more frequently by both men and women than attempts to discourage their entry into treatment, but only the encouragement of the spouse or opposite-sexed partner was significantly related to treatment outcome.", "contents": "Interpersonal relationships in heroin use by men and women and their role in treatment outcome. The majority of both male and female heroin addicts entering a city treatment program were introduced to heroin by a male. But by contrast with the males, females were in many cases introduced to heroin by another woman, more often used drugs with persons of both sexes, and were more likely to be living with a current or former heroin user at intake. Encouragement to give up drugs was reported more frequently by both men and women than attempts to discourage their entry into treatment, but only the encouragement of the spouse or opposite-sexed partner was significantly related to treatment outcome."} {"id": "PMID:1254364", "title": "Contingent naloxone treatment of the narcotic addict: a pilot study.", "content": "In a community-based abstinence program, 108 chronic heroin abusers, paroled from Maryland correctional institutions, were administered the narcotic antagonist, naloxone, in escalating 500 mg dosages to a daily maximum dosage of 2,000 mg when either urine analysis indicated narcotic drug use or unexcused absences led to the suspicion of narcotic intake. Dosage was then continued at the maximum level until the record again indicated abstinence. This approach was regarded as such a distinct departure from customary antagonist administration that a pilot investigation of its effectiveness was undertaken. Six month outcome data on all patients were constrasted with those of an historical comparison group previously treated in the same clinic without naloxone administration. Both groups were equivalent on all criminal history, demographic, and prognostic variables. The group receiving contingent naloxone administration showed a significantly lower institutionalization rate (8%) than that for the reference sample (37%). Complete abstinence rates were also in favor of the naloxone group (38 vs. 12%).", "contents": "Contingent naloxone treatment of the narcotic addict: a pilot study. In a community-based abstinence program, 108 chronic heroin abusers, paroled from Maryland correctional institutions, were administered the narcotic antagonist, naloxone, in escalating 500 mg dosages to a daily maximum dosage of 2,000 mg when either urine analysis indicated narcotic drug use or unexcused absences led to the suspicion of narcotic intake. Dosage was then continued at the maximum level until the record again indicated abstinence. This approach was regarded as such a distinct departure from customary antagonist administration that a pilot investigation of its effectiveness was undertaken. Six month outcome data on all patients were constrasted with those of an historical comparison group previously treated in the same clinic without naloxone administration. Both groups were equivalent on all criminal history, demographic, and prognostic variables. The group receiving contingent naloxone administration showed a significantly lower institutionalization rate (8%) than that for the reference sample (37%). Complete abstinence rates were also in favor of the naloxone group (38 vs. 12%)."} {"id": "PMID:1254365", "title": "Demographic characteristics of groups classified by patterns of multiple drug abuse: a 1969-1971 sample.", "content": "Patient characteristics are described in relation to pretreatment usage combinations of eight classes of illicit drugs for 11,380 drug abusers admitted between 1969 and 1971 to drug treatment centers participating in the NIDA-TCU Drug Abuse Reporting Program. From these data, nine basic patterns of drug use were defined. The most frequent, involving the daily use of heroin or other opioids only, characterized 27% of the patients. Four patterns involving heroin (at least weekly) with various combinations of cocaine, barbiturates, and marijuana accounted for another 29%, two patterns of polydrug use (three or more nonopioid drugs, with and without opioids daily) included 16%, and the remaining 28% of the patients were represented by patterns of a less specific nature. The distribution of patients across drug-use patterns was unrelated to sex, but was associated with race-ethnic background and age.", "contents": "Demographic characteristics of groups classified by patterns of multiple drug abuse: a 1969-1971 sample. Patient characteristics are described in relation to pretreatment usage combinations of eight classes of illicit drugs for 11,380 drug abusers admitted between 1969 and 1971 to drug treatment centers participating in the NIDA-TCU Drug Abuse Reporting Program. From these data, nine basic patterns of drug use were defined. The most frequent, involving the daily use of heroin or other opioids only, characterized 27% of the patients. Four patterns involving heroin (at least weekly) with various combinations of cocaine, barbiturates, and marijuana accounted for another 29%, two patterns of polydrug use (three or more nonopioid drugs, with and without opioids daily) included 16%, and the remaining 28% of the patients were represented by patterns of a less specific nature. The distribution of patients across drug-use patterns was unrelated to sex, but was associated with race-ethnic background and age."} {"id": "PMID:1254366", "title": "Incidence of daily drug use as reported by a population of Thai partners working near United States military installations: a preliminary study.", "content": "A survey of 497 women, all of whom solicited partners from among American soldiers, indicated that 15% of this Thai population uses drugs and/or alcohol daily. Since behavioral observation made during this interview, as well as inconsistencies in responses on the survey, strongly suggested a reluctance to report drug use, it is judged that reported drug use represents an underestimate of true daily usage rate. The influence of transactions between these Thai women and their American associates upon drug use in each group was assessed from the perspective of the Thai informants. There appears to neither a great deal of drug use by Americans induced by interpersonal relationships with these Thai women, nor a great deal of Thai drug use which can be directly attributed to the influence of American soldiers. Alternate methods of data collection are suggested to substantiate this finding. An in-depth study of the relations established between these respondents and their American partners is planned to better interpret these results.", "contents": "Incidence of daily drug use as reported by a population of Thai partners working near United States military installations: a preliminary study. A survey of 497 women, all of whom solicited partners from among American soldiers, indicated that 15% of this Thai population uses drugs and/or alcohol daily. Since behavioral observation made during this interview, as well as inconsistencies in responses on the survey, strongly suggested a reluctance to report drug use, it is judged that reported drug use represents an underestimate of true daily usage rate. The influence of transactions between these Thai women and their American associates upon drug use in each group was assessed from the perspective of the Thai informants. There appears to neither a great deal of drug use by Americans induced by interpersonal relationships with these Thai women, nor a great deal of Thai drug use which can be directly attributed to the influence of American soldiers. Alternate methods of data collection are suggested to substantiate this finding. An in-depth study of the relations established between these respondents and their American partners is planned to better interpret these results."} {"id": "PMID:1254367", "title": "Doxepin: a useful adjunct in the treatment of heroin addicts in a methadone program.", "content": "An uncontrolled trial of doxepin as an adjunct to treatment of heroin addicts in a methadone program was performed over a 14-month period. Approximately 10% (27) of the program's population utilized a mean of 73 mg of doxepin, usually briefly, and beneficial results were noted in 93% (25). One adverse reaction occurred. No instance of habituation or addiction was noted. A controlled study is warranted to confirm the impression that doxepin represents a useful adjunct in the treatment of heroin addicts in a methadone program.", "contents": "Doxepin: a useful adjunct in the treatment of heroin addicts in a methadone program. An uncontrolled trial of doxepin as an adjunct to treatment of heroin addicts in a methadone program was performed over a 14-month period. Approximately 10% (27) of the program's population utilized a mean of 73 mg of doxepin, usually briefly, and beneficial results were noted in 93% (25). One adverse reaction occurred. No instance of habituation or addiction was noted. A controlled study is warranted to confirm the impression that doxepin represents a useful adjunct in the treatment of heroin addicts in a methadone program."} {"id": "PMID:1254368", "title": "Alcoholism as blaming the alcoholic.", "content": "Theories of alcoholism tend to blame the alcoholic by implying that most American drinkers have an ability, which the alcoholic lacks, to drink without problems. The presence or absence of this ability or capacity presumably accounts for the incidence of alcohol problems in society. But we normally apply the idea of an ability or a capacity only after an individual has been exposed to the risk of problems from a hazard or difficult task, and when an individual avoids these problems by their efforts. On this point survey data reveal that most American drinkers have a rather limited exposure to alcohol and are not at risk for problems. It is likely that it is this low exposure to alcohol-rather than some drinking ability-that accounts for the absence of problems. Moreover, the entire practice of treating drinking and the occurrence of problems in the idiom of individual abilities, capacities, or control can be shown to be incorrect and is systematically misleading. A public health approach to alcohol problems is needed that identifies the risks for all associated with hazardous intakes of alcohol and that seeks to reduce these hazards chiefly by reducing the overall consumption of alcohol.", "contents": "Alcoholism as blaming the alcoholic. Theories of alcoholism tend to blame the alcoholic by implying that most American drinkers have an ability, which the alcoholic lacks, to drink without problems. The presence or absence of this ability or capacity presumably accounts for the incidence of alcohol problems in society. But we normally apply the idea of an ability or a capacity only after an individual has been exposed to the risk of problems from a hazard or difficult task, and when an individual avoids these problems by their efforts. On this point survey data reveal that most American drinkers have a rather limited exposure to alcohol and are not at risk for problems. It is likely that it is this low exposure to alcohol-rather than some drinking ability-that accounts for the absence of problems. Moreover, the entire practice of treating drinking and the occurrence of problems in the idiom of individual abilities, capacities, or control can be shown to be incorrect and is systematically misleading. A public health approach to alcohol problems is needed that identifies the risks for all associated with hazardous intakes of alcohol and that seeks to reduce these hazards chiefly by reducing the overall consumption of alcohol."} {"id": "PMID:1254369", "title": "Drug flashbacks. II. Some additional findings.", "content": "A subsample was drawn from an earlier collection of data in order to answer a number of questions related to \"acid\" (LSD, STP) flashbacks. Acid users who reported flashbacks also reported significantly more marijuana use than those who did not; the two groups did not differ on use of other drugs, including acid. Simple correlations and multiple regression analyses both showed extent of marijuana use to be the only drug variable significantly related to acid flashbacks. No optimal combination of marijuana and acid improved flashback prediction. Among acid users, correlations between amounts of use for various drugs were high and significant, excepting only the marijuana-acid correlation.", "contents": "Drug flashbacks. II. Some additional findings. A subsample was drawn from an earlier collection of data in order to answer a number of questions related to \"acid\" (LSD, STP) flashbacks. Acid users who reported flashbacks also reported significantly more marijuana use than those who did not; the two groups did not differ on use of other drugs, including acid. Simple correlations and multiple regression analyses both showed extent of marijuana use to be the only drug variable significantly related to acid flashbacks. No optimal combination of marijuana and acid improved flashback prediction. Among acid users, correlations between amounts of use for various drugs were high and significant, excepting only the marijuana-acid correlation."} {"id": "PMID:1254370", "title": "Drug patterns in the chronic marijuana user.", "content": "The study examined the drug patterns and attitudes of a heavy marijuana user sample drawn from the local \"counter-culture.\" The results indicate that the heavier marijuana user has a different subjective attitude and perception of the drug's effect than a light user. Second, multiple drug usage is, in general, the current and accepted mode within the sample. Finally, it appears that age of initial usage of a specific agent, duration, frequency of usage, and perceived drug effects may be dependent variables with reference to heavy marijuana and multiple drug usage. With respect to these variables, the question arises concerning what proportion of lighter drug using samples may, with time, adopt heavier and more varied drug patterns.", "contents": "Drug patterns in the chronic marijuana user. The study examined the drug patterns and attitudes of a heavy marijuana user sample drawn from the local \"counter-culture.\" The results indicate that the heavier marijuana user has a different subjective attitude and perception of the drug's effect than a light user. Second, multiple drug usage is, in general, the current and accepted mode within the sample. Finally, it appears that age of initial usage of a specific agent, duration, frequency of usage, and perceived drug effects may be dependent variables with reference to heavy marijuana and multiple drug usage. With respect to these variables, the question arises concerning what proportion of lighter drug using samples may, with time, adopt heavier and more varied drug patterns."} {"id": "PMID:1254371", "title": "The personality of the cigarette smoker: some empirical data.", "content": "Smokers and nonsmokers are compared in terms of (1) psychological needs, (2) self-descriptions, (3) self-esteem, (4) academic achievement in high school and college, and (5) marijuana use. On the EPPS smokers scored significantly higher on the needs for Autonomy (p less than .01), Change (p less than .02) and Heterosexuality (p less than .05), while nonsmokers scored higher on the needs for Achievement (p less than .05), Deference (p less than .001), and Order (p less than .001). Smokers rated themselves as being more sociable (p less than .05), while nonsmokers rated themselves as being more careful (p less than .05) and reliable (p less than .05). While the two groups did not differ on a measure of self-esteem, smokers were found to have lower grades in high school (p less than .05) and college (p less than .01) and to be more likely (p less than .0001) to use marijuana. These findings are compared to the results of previous studies and the need for future research is discussed.", "contents": "The personality of the cigarette smoker: some empirical data. Smokers and nonsmokers are compared in terms of (1) psychological needs, (2) self-descriptions, (3) self-esteem, (4) academic achievement in high school and college, and (5) marijuana use. On the EPPS smokers scored significantly higher on the needs for Autonomy (p less than .01), Change (p less than .02) and Heterosexuality (p less than .05), while nonsmokers scored higher on the needs for Achievement (p less than .05), Deference (p less than .001), and Order (p less than .001). Smokers rated themselves as being more sociable (p less than .05), while nonsmokers rated themselves as being more careful (p less than .05) and reliable (p less than .05). While the two groups did not differ on a measure of self-esteem, smokers were found to have lower grades in high school (p less than .05) and college (p less than .01) and to be more likely (p less than .0001) to use marijuana. These findings are compared to the results of previous studies and the need for future research is discussed."} {"id": "PMID:1254372", "title": "Addiction to diazepam.", "content": "Literature is reviewed which raises the question of diazepam's addicting potential. To explore this issue, 50 subjects referred from medical, surgical, and psychiatric clinics were evaluated by interview regarding their use of diazepam. Replies to a standardized interview were combined with physicians' ratings of addiction under two conditions: without and then with the knowledge that the drug in question was diazepam. A computer-aided analysis of these data, including a correlation matrix, revealed surprisingly strong evidence for diazepam's capacity to elicit tolerance and withdrawal in this sample. Psychiatric patients were no more \"addiction-prone\" in this regard than patients given diazepam for medical conditions. Of equal significance, physicians' impressions of addiction were significantly altered toward a more favorable view when they learned that the drug in question was diazepam. Implications for psychiatric and medical practice are discussed, and suggestions for further controlled research offered.", "contents": "Addiction to diazepam. Literature is reviewed which raises the question of diazepam's addicting potential. To explore this issue, 50 subjects referred from medical, surgical, and psychiatric clinics were evaluated by interview regarding their use of diazepam. Replies to a standardized interview were combined with physicians' ratings of addiction under two conditions: without and then with the knowledge that the drug in question was diazepam. A computer-aided analysis of these data, including a correlation matrix, revealed surprisingly strong evidence for diazepam's capacity to elicit tolerance and withdrawal in this sample. Psychiatric patients were no more \"addiction-prone\" in this regard than patients given diazepam for medical conditions. Of equal significance, physicians' impressions of addiction were significantly altered toward a more favorable view when they learned that the drug in question was diazepam. Implications for psychiatric and medical practice are discussed, and suggestions for further controlled research offered."} {"id": "PMID:1254373", "title": "Inhibitory effect of an intravenous glucose load on basal and insulin-stimulated gastric acid secretion in man.", "content": "The effect of intravenous glucose on basal and insulin-stimulated gastric acid secretion was investigated in a crossover study on four healthy subjects. Acid output was measured by means of intragastric titration and a telemetering capsule; serum-gastrin and blood glucose levels were measured in 15-minute-intervals. Two different experiments were carried out on each subject. After one basal hour in series (a), 2 ml saline, and in series (b), 0.2 U/kg b. w. glucagon-free insulin were injected intravenously. Two hours later, in both series 0.66 g/kg b. w. glucose were given by rapid i.v. infusion, and the experiment continued for another hour. Hyperglycemia was found to depress significantly basal as well as insulin-stimulated acid secretion, while serum-gastrin levels showed no systematic variation. On the basis of these findings and of earlier studies in animals, it is concluded that the inhibitory effect of hyperglycemia is due to a central action, i.e., an increased activity of the satiety center.", "contents": "Inhibitory effect of an intravenous glucose load on basal and insulin-stimulated gastric acid secretion in man. The effect of intravenous glucose on basal and insulin-stimulated gastric acid secretion was investigated in a crossover study on four healthy subjects. Acid output was measured by means of intragastric titration and a telemetering capsule; serum-gastrin and blood glucose levels were measured in 15-minute-intervals. Two different experiments were carried out on each subject. After one basal hour in series (a), 2 ml saline, and in series (b), 0.2 U/kg b. w. glucagon-free insulin were injected intravenously. Two hours later, in both series 0.66 g/kg b. w. glucose were given by rapid i.v. infusion, and the experiment continued for another hour. Hyperglycemia was found to depress significantly basal as well as insulin-stimulated acid secretion, while serum-gastrin levels showed no systematic variation. On the basis of these findings and of earlier studies in animals, it is concluded that the inhibitory effect of hyperglycemia is due to a central action, i.e., an increased activity of the satiety center."} {"id": "PMID:1254374", "title": "Inhibition of prostaglandin potentiated formalin induced arthritis with non-steroid antiphlogistics.", "content": "The PGE2 potentiated formalin arthritis can be only temporarily influenced by indomethacin. Azapropazone had a good therapeutic effect on chronic inflammation. According to the enzyme histochemical studies, azapropazone enhanced oxidative enzyme activity. This phenomenon may be interpreted as a sign of a favorable effect.", "contents": "Inhibition of prostaglandin potentiated formalin induced arthritis with non-steroid antiphlogistics. The PGE2 potentiated formalin arthritis can be only temporarily influenced by indomethacin. Azapropazone had a good therapeutic effect on chronic inflammation. According to the enzyme histochemical studies, azapropazone enhanced oxidative enzyme activity. This phenomenon may be interpreted as a sign of a favorable effect."} {"id": "PMID:1254375", "title": "Probenecid and the rat kidney: investigations by renal enzyme excretion technique.", "content": "Probenecid in doses of 640 mg/kg was administered to rats by the oral route, and the changes in five important enzymatic activities of urine were recorded thereafter for two days. The resluts exclude that probenecid impairs tubular reabsorption of low molecular weight protein, as urinary muramidase activity was not found increased. On the other hand, increased activities were encountered in those enzymatic activities in urine which derive from the renal tubular cells (ALD, G-6-PDH, LDH). These observations point towards a nephrotoxic effect of probenecid, which, however, is only of very low degree, as other \"standard\" enzymatic activities of urine, such as alkaline phosphatase, remained unchanged.", "contents": "Probenecid and the rat kidney: investigations by renal enzyme excretion technique. Probenecid in doses of 640 mg/kg was administered to rats by the oral route, and the changes in five important enzymatic activities of urine were recorded thereafter for two days. The resluts exclude that probenecid impairs tubular reabsorption of low molecular weight protein, as urinary muramidase activity was not found increased. On the other hand, increased activities were encountered in those enzymatic activities in urine which derive from the renal tubular cells (ALD, G-6-PDH, LDH). These observations point towards a nephrotoxic effect of probenecid, which, however, is only of very low degree, as other \"standard\" enzymatic activities of urine, such as alkaline phosphatase, remained unchanged."} {"id": "PMID:1254376", "title": "Application of a simple fluorometric method on absorption of canrenone.", "content": "The absorption of canrenone, the major metabolite of spironolactone, was studied by a simple fluorometric method in 30 healthy subjects. Two different pharmaceutical formulations were compared on absorption, and only a negligible difference was found between the micronized and balled-milled form. Canrenone in both formulations was well absorbed, whereas spironolactone absorption was slower. Mattingly's fluorometric assay proved to be a simple method to evaluate the absorption of canrenone.", "contents": "Application of a simple fluorometric method on absorption of canrenone. The absorption of canrenone, the major metabolite of spironolactone, was studied by a simple fluorometric method in 30 healthy subjects. Two different pharmaceutical formulations were compared on absorption, and only a negligible difference was found between the micronized and balled-milled form. Canrenone in both formulations was well absorbed, whereas spironolactone absorption was slower. Mattingly's fluorometric assay proved to be a simple method to evaluate the absorption of canrenone."} {"id": "PMID:1254377", "title": "[Concentration course of Na-Penicillin G in wound secretions following vascular surgery].", "content": "After infusion of 10 and 20 M.I.U. of Na-penicilline G, the concentrations in serum, wound exudation, and urine were analysed, at equal points of time, following vascular reconstruction; pharmacokinetic data were calculated as well. The importance of local concentration of antibiotics for therapy and prevention of infections is emphasized - according to pharmacokinetics - in relation to the blood level. Simultaneously, the influence of pathological changes is discussed and represented by a brief case follow-up.", "contents": "[Concentration course of Na-Penicillin G in wound secretions following vascular surgery]. After infusion of 10 and 20 M.I.U. of Na-penicilline G, the concentrations in serum, wound exudation, and urine were analysed, at equal points of time, following vascular reconstruction; pharmacokinetic data were calculated as well. The importance of local concentration of antibiotics for therapy and prevention of infections is emphasized - according to pharmacokinetics - in relation to the blood level. Simultaneously, the influence of pathological changes is discussed and represented by a brief case follow-up."} {"id": "PMID:1254378", "title": "[The influence of xanthinol nicotinate and of a hyperosmolar solution on the motility of the colon].", "content": "The effect of Xantinol nicotinate and of hyperosmolar solution upon colonic motility of man was examined in five patients with tranverse preternatural anus by means of intraluminal tonometry. During these examinations, a clear increase of the normal colonic motility could proved as caused by Xantinol nicotinate. According to previous animal experimental tests, and also based on our own clinical experiences, Xantinol nicotinate may be recommended for surgical practice as a reliable stimulant for colonic motility.", "contents": "[The influence of xanthinol nicotinate and of a hyperosmolar solution on the motility of the colon]. The effect of Xantinol nicotinate and of hyperosmolar solution upon colonic motility of man was examined in five patients with tranverse preternatural anus by means of intraluminal tonometry. During these examinations, a clear increase of the normal colonic motility could proved as caused by Xantinol nicotinate. According to previous animal experimental tests, and also based on our own clinical experiences, Xantinol nicotinate may be recommended for surgical practice as a reliable stimulant for colonic motility."} {"id": "PMID:1254380", "title": "Intestinal peptidase activity following whole-body irradiation in mice.", "content": "Dipeptidase activity (Gly-L-Leucine, L. Leu-Glycine, Gly-L-Phe, L Phe-Gly) was measured in the cytoplasmic fraction of the small bowel mucosa of mice eating three synthetic, defined formula, diets or Purina Chow. The activity/milligram protein of all peptidases was found to be reduced seven days after the last of six weekly exposures to 400 rads (Cobalt 60). The magnitude of reduction varied from half the control value for L-Leu-Glycine peptidase to between one fourth and one fifth the control values for the other three peptidases. These findings may partly explain the improved tolerance to radiation in mice eating a diet containing amino acids (protein hydrolysate) instead of whole protein.", "contents": "Intestinal peptidase activity following whole-body irradiation in mice. Dipeptidase activity (Gly-L-Leucine, L. Leu-Glycine, Gly-L-Phe, L Phe-Gly) was measured in the cytoplasmic fraction of the small bowel mucosa of mice eating three synthetic, defined formula, diets or Purina Chow. The activity/milligram protein of all peptidases was found to be reduced seven days after the last of six weekly exposures to 400 rads (Cobalt 60). The magnitude of reduction varied from half the control value for L-Leu-Glycine peptidase to between one fourth and one fifth the control values for the other three peptidases. These findings may partly explain the improved tolerance to radiation in mice eating a diet containing amino acids (protein hydrolysate) instead of whole protein."} {"id": "PMID:1254381", "title": "Comparison of renal excretion of chloramphenicol in patients with chronic pyelonephritis, glomerulonephritis and polycystic kidneys.", "content": "In patients with chronic pyelonephritis, glomerulonephritis and polycystic kidneys, decrease in renal clearance of chloramphenicol (CCHL) is related to a decrease in the clearance of inulin (Cin). The rate of decrease of CCHL is relatively slower than that of Cin. The findings attest to an increased excretion of chloramphenicol by residual nephrons. The groups investigated did not display any significant differences in the relation between CCHL and Cin. The findings indicate that changes in the excretion of chloramphenicol by residual nephrons are not related to the primary pathological process responsible for the impairment of the renal parenchyma.", "contents": "Comparison of renal excretion of chloramphenicol in patients with chronic pyelonephritis, glomerulonephritis and polycystic kidneys. In patients with chronic pyelonephritis, glomerulonephritis and polycystic kidneys, decrease in renal clearance of chloramphenicol (CCHL) is related to a decrease in the clearance of inulin (Cin). The rate of decrease of CCHL is relatively slower than that of Cin. The findings attest to an increased excretion of chloramphenicol by residual nephrons. The groups investigated did not display any significant differences in the relation between CCHL and Cin. The findings indicate that changes in the excretion of chloramphenicol by residual nephrons are not related to the primary pathological process responsible for the impairment of the renal parenchyma."} {"id": "PMID:1254382", "title": "The human biotransformation of nalidixic acid.", "content": "Authors have developed new chemical methods for studying the human metabolism of nalidixic acid. The methods are suited for the quantitative determination of nalidixic acid, hydroxynalidixic acid, nalidixic acid glucuronide, hydroxynalidixic acid-glucuronide, and of free and total glucuronic acid excretion. The total urinary excretion of NA and its metabolites was found to be 50 to 100% of the ingested dose. The percentual distribution of the individual metabolites was as follows: NA 0,5-5, HNA2,5-6, NAG24-80, and HNAG11-26%. It was unanimously proved by enzymatic decomposition and specific chemical reactions that the excreted conjugates were monoglucuronides. The significance of individual differences, bilirubin metabolism, urinary pH and the pharmacokinetical behaviour of the individual metabolites is discussed from the therapeutic view.", "contents": "The human biotransformation of nalidixic acid. Authors have developed new chemical methods for studying the human metabolism of nalidixic acid. The methods are suited for the quantitative determination of nalidixic acid, hydroxynalidixic acid, nalidixic acid glucuronide, hydroxynalidixic acid-glucuronide, and of free and total glucuronic acid excretion. The total urinary excretion of NA and its metabolites was found to be 50 to 100% of the ingested dose. The percentual distribution of the individual metabolites was as follows: NA 0,5-5, HNA2,5-6, NAG24-80, and HNAG11-26%. It was unanimously proved by enzymatic decomposition and specific chemical reactions that the excreted conjugates were monoglucuronides. The significance of individual differences, bilirubin metabolism, urinary pH and the pharmacokinetical behaviour of the individual metabolites is discussed from the therapeutic view."} {"id": "PMID:1254383", "title": "Effect of tuberculostatic agents on the response of serum growth hormone and immunoreactive insulin to intravenous tolbutamide, and on the half-life of tolbutamide.", "content": "The effect of drugs used in the chemotherapy of tuberculosis on blood glucose, serum immunoreactive insulin and serum growth hormone, and on the half-life of tolbutamide, were studied in 16 patients with tuberculosis just before starting treatment and four weeks later using an intravenous tolbutamide test. The maximum fall of blood sugar was about 30% on both test occasions. The peak values of serum growth hormone before and after treatment (15.6+/-3.1 ng/ml and 17.3+/-2.9 ng/ml), and the maximum values of serum insulin before or after treatment (37.6+/-5.3muU/ml and 45.6+/-7.0 muU/ml) did not differ significantly from one another. The levels of serum insulin remained slightly higher in the test from 10 minutes onwards after treatment than before, but this was not associated with any particular tuberculostatic drug combination. The half-life of tolbutamide decreased by 43% and the serum concentration of tolbutamide decreased at 180 minutes by 30% and at 360 minutes by 49% after treatment in comparison with the pretreatment values in the patients receiving rifampicin in their drug combination. In patients receiving other tuberculostatic agents, no significant changes were observed.", "contents": "Effect of tuberculostatic agents on the response of serum growth hormone and immunoreactive insulin to intravenous tolbutamide, and on the half-life of tolbutamide. The effect of drugs used in the chemotherapy of tuberculosis on blood glucose, serum immunoreactive insulin and serum growth hormone, and on the half-life of tolbutamide, were studied in 16 patients with tuberculosis just before starting treatment and four weeks later using an intravenous tolbutamide test. The maximum fall of blood sugar was about 30% on both test occasions. The peak values of serum growth hormone before and after treatment (15.6+/-3.1 ng/ml and 17.3+/-2.9 ng/ml), and the maximum values of serum insulin before or after treatment (37.6+/-5.3muU/ml and 45.6+/-7.0 muU/ml) did not differ significantly from one another. The levels of serum insulin remained slightly higher in the test from 10 minutes onwards after treatment than before, but this was not associated with any particular tuberculostatic drug combination. The half-life of tolbutamide decreased by 43% and the serum concentration of tolbutamide decreased at 180 minutes by 30% and at 360 minutes by 49% after treatment in comparison with the pretreatment values in the patients receiving rifampicin in their drug combination. In patients receiving other tuberculostatic agents, no significant changes were observed."} {"id": "PMID:1254385", "title": "Measurement of blood flow in skin with an intact vascular pedicle.", "content": "An experimental model was devised to confirm directly the validity of total skin blood flow measurement, as postulated by Sejrsen. A section of skin in the groin of the rat was prepared, which contained an intact artery and vein. Both of these were direct branches of the femoral vessels. When 133Xe was injected intradermally in saline solution, it was demonstrated that a sham isolated vascular pedicle cleared the isotope, and that the clearance was biexpoential, suggesting two compartments. When the vascualr pedicle was ligated, thereby removing direct blood flow to the piece of skin, the 133Xe clearance curve was monexponential. It is concluded that the rapid portion of the biexponential clearance curve, as analyzed by Sejrsen, does represent the dermal vascular components of isotope clearance, and that measurement of cutaneous blood flow by this method is a valid and useful technique. Results using this technique to follow rejection in a new skin transplant model are presented.", "contents": "Measurement of blood flow in skin with an intact vascular pedicle. An experimental model was devised to confirm directly the validity of total skin blood flow measurement, as postulated by Sejrsen. A section of skin in the groin of the rat was prepared, which contained an intact artery and vein. Both of these were direct branches of the femoral vessels. When 133Xe was injected intradermally in saline solution, it was demonstrated that a sham isolated vascular pedicle cleared the isotope, and that the clearance was biexpoential, suggesting two compartments. When the vascualr pedicle was ligated, thereby removing direct blood flow to the piece of skin, the 133Xe clearance curve was monexponential. It is concluded that the rapid portion of the biexponential clearance curve, as analyzed by Sejrsen, does represent the dermal vascular components of isotope clearance, and that measurement of cutaneous blood flow by this method is a valid and useful technique. Results using this technique to follow rejection in a new skin transplant model are presented."} {"id": "PMID:1254386", "title": "Trichophyton violaceum infection in an Indian school.", "content": "Trichophyton violaceum infection was found in 26% of 69 children attending a public boarding school. The possible source of infection may have been the adult women from the gypsy community discussed. Treatment with systemic griseofulvin and external sulphur salicylic ointment eliminated the infection in all affected individuals.", "contents": "Trichophyton violaceum infection in an Indian school. Trichophyton violaceum infection was found in 26% of 69 children attending a public boarding school. The possible source of infection may have been the adult women from the gypsy community discussed. Treatment with systemic griseofulvin and external sulphur salicylic ointment eliminated the infection in all affected individuals."} {"id": "PMID:1254387", "title": "Clofazimine in dermatology.", "content": "In dermatology, patients with nodosum leprosum and discoid lupus erythematosus are benefited by clofazimine therapy. Its use in other autoimmune diseases has to be considered. Patients with lupus pernio may respond to this regime, but further prolonged trials will have to be undertaken.", "contents": "Clofazimine in dermatology. In dermatology, patients with nodosum leprosum and discoid lupus erythematosus are benefited by clofazimine therapy. Its use in other autoimmune diseases has to be considered. Patients with lupus pernio may respond to this regime, but further prolonged trials will have to be undertaken."} {"id": "PMID:1254399", "title": "A study of thirty right hepatic arteries.", "content": "Thirty right hepatic arteries discovered among 137 celiomesenteric angiographies show the high frequency (22%) of this variation. Radiologic anatomy of the right hepatic artery was discussed; with the exception of one atheromatous stenosis, the pathologic findings of the right hepatic artery and its terminal branches illustrate the development of a regional disease (12 cases or 40%). This assumed pathology is divided half in pancreatic causes (neoplasm, pancreatitis, pseudocysts) and half in hepatobiliary causes (metastatic cancer of the liver, cancer of the hilus, cirrhosis, hydatid cyst, alveolar echinococcosis or angioma). Five times the surgical technic was modified because of the right hepatic artery. Since these observations were made, we are studying the consequences of this hepatic artery over surgical technics and the approach to the various segments of this artery.", "contents": "A study of thirty right hepatic arteries. Thirty right hepatic arteries discovered among 137 celiomesenteric angiographies show the high frequency (22%) of this variation. Radiologic anatomy of the right hepatic artery was discussed; with the exception of one atheromatous stenosis, the pathologic findings of the right hepatic artery and its terminal branches illustrate the development of a regional disease (12 cases or 40%). This assumed pathology is divided half in pancreatic causes (neoplasm, pancreatitis, pseudocysts) and half in hepatobiliary causes (metastatic cancer of the liver, cancer of the hilus, cirrhosis, hydatid cyst, alveolar echinococcosis or angioma). Five times the surgical technic was modified because of the right hepatic artery. Since these observations were made, we are studying the consequences of this hepatic artery over surgical technics and the approach to the various segments of this artery."} {"id": "PMID:1254407", "title": "Anti-herpes activity of adenine arabinoside monophosphate.", "content": "Adenine arabinoside monophosphate (Ara-AMP) demonstrated antiviral activity equivalent to adenine arabinoside (Ara-A) against herpesvirus Types 1 and 2 in tissue culture. Against established herpes virus Type 1 epithelial keratitis in rabbits, Ara-AMP 2 per cent was comparable in efficacy to Ara-A 3 per cent, and Ara-AMP 20 per cent was superior to Ara-A 3 per cent. These results are especially significant in that Ara-A's high solubility will permit (1) more concentrated formulations to be presented topically and (2) adequate absorption by parenteral routes with smaller fluid loads than required for Ara-A.", "contents": "Anti-herpes activity of adenine arabinoside monophosphate. Adenine arabinoside monophosphate (Ara-AMP) demonstrated antiviral activity equivalent to adenine arabinoside (Ara-A) against herpesvirus Types 1 and 2 in tissue culture. Against established herpes virus Type 1 epithelial keratitis in rabbits, Ara-AMP 2 per cent was comparable in efficacy to Ara-A 3 per cent, and Ara-AMP 20 per cent was superior to Ara-A 3 per cent. These results are especially significant in that Ara-A's high solubility will permit (1) more concentrated formulations to be presented topically and (2) adequate absorption by parenteral routes with smaller fluid loads than required for Ara-A."} {"id": "PMID:1254408", "title": "Deposits of mucosubstances on the cornea by topical chloramphenicol: an electron microscopic study.", "content": "Chloramphenicol was instilled into rabbit eyes and five days later the corneal surface was examined by scanning electron microscopy. The corneal surface was roughened and showed a proliferative appearance. Examination of thin sections of the cornea by transmission electron microscope showed that the corneal surface stained strongly with alcian blue. It was thus supposed to be a deposit of mucosubstances. Mucosubstances increase pathogenicity of bacteria and, therefore, this deposit may accelerate Pseudomonas keratitis after chloramphenicol application.", "contents": "Deposits of mucosubstances on the cornea by topical chloramphenicol: an electron microscopic study. Chloramphenicol was instilled into rabbit eyes and five days later the corneal surface was examined by scanning electron microscopy. The corneal surface was roughened and showed a proliferative appearance. Examination of thin sections of the cornea by transmission electron microscope showed that the corneal surface stained strongly with alcian blue. It was thus supposed to be a deposit of mucosubstances. Mucosubstances increase pathogenicity of bacteria and, therefore, this deposit may accelerate Pseudomonas keratitis after chloramphenicol application."} {"id": "PMID:1254409", "title": "Dissecting ocular tissue for intraocular drug studies.", "content": "This report describes a convenient reproducible ocular dissection technique which has important applications for ocular antimicrobial penetration studies. Different ocular tissues can be sectioned while frozen and then plated directly on culture medium containing the test organism; after the zones of bacterial inhibition are measured at 18 hours following incubation, the tissue specimens are weighed providing more reliable evidence regarding drug concentrations. In such a fashion, a drug can be administered topically, subconjunctivally, or systematically, and assayed from the cornea to the optic nerve at various time intervals. Analysis of antibiotic in the vitreous body, which has important application in the therapy of endophthalmitis, can be routinely performed in the experimental model.", "contents": "Dissecting ocular tissue for intraocular drug studies. This report describes a convenient reproducible ocular dissection technique which has important applications for ocular antimicrobial penetration studies. Different ocular tissues can be sectioned while frozen and then plated directly on culture medium containing the test organism; after the zones of bacterial inhibition are measured at 18 hours following incubation, the tissue specimens are weighed providing more reliable evidence regarding drug concentrations. In such a fashion, a drug can be administered topically, subconjunctivally, or systematically, and assayed from the cornea to the optic nerve at various time intervals. Analysis of antibiotic in the vitreous body, which has important application in the therapy of endophthalmitis, can be routinely performed in the experimental model."} {"id": "PMID:1254410", "title": "Chlorampenicol retention on, and penetration into, the rabbit eye.", "content": "The retention of the antibiotic chloramphenicol on, and penetration into, the rabbit eye has been compared following administration in two vehicles. Samples were taken of both aqueous humor and a washing fluid applied to the conjunctival surface and the concentration of 14C-chloramphenicol determined. Greater tear film and aqueous humor drug concentrations, which are effective against many organisms, were found with a vehicle which enhanced retention time on the ocular surfaces.", "contents": "Chlorampenicol retention on, and penetration into, the rabbit eye. The retention of the antibiotic chloramphenicol on, and penetration into, the rabbit eye has been compared following administration in two vehicles. Samples were taken of both aqueous humor and a washing fluid applied to the conjunctival surface and the concentration of 14C-chloramphenicol determined. Greater tear film and aqueous humor drug concentrations, which are effective against many organisms, were found with a vehicle which enhanced retention time on the ocular surfaces."} {"id": "PMID:1254411", "title": "Steroid metabolism in ocular tissues of the rabbit.", "content": "The metabolism of cortisol and other steroids was studied in normal untreated rabbit iris-ciliary body and cornea as part of an investigation into the mechanism of glucocorticoid-induced glaucoma. Cortisol is readily converted to the inactive metabolite cortisone by these eye tissues indicating the presence of an 11beta-oxidoreductase system. This reaction is reversible with cortisone being converted to cortisol in the presence of appropriate cofactor. However, due to the absence of a (or as yet undetectable) cortisol-A-ring-reductase system (rate-limiting reaction) the steroid is not irreversibly metabolized to biologically inactive compounds. The 11beta-oxidoreductase system readily converts other C21-11beta-hydroxysteroids, such as corticosterone, to its appropriate C21-11-ketosteroid (11-dehydrocorticosterone). Some C21-steroids lacking the 11-hydroxyl group (11-deoxycortisol, 11-deoxycorticosterone) remain virtually unmetabolized (exception to this was found with progesterone). Evidence of a C21-steroid A-ring reductase system was found only when cortisone and progesterone were used as substrates. However, testosterone a C19 steroid was converted to clearly identifiable A-ring reduced and 17beta-and 3alpha(beta)-oxidoreduced metabolites, thus indicating the presence of testosterone A-ring reductase, 17beta-and 3alpha(beta)-oxidoreductase systems in the eye tissues studied. The presence of a steroid 5alpha(beta)-reductase for some steroids but not for cortisol indicates a distinct substrate specificity for this enzyme system in the eye tissues.", "contents": "Steroid metabolism in ocular tissues of the rabbit. The metabolism of cortisol and other steroids was studied in normal untreated rabbit iris-ciliary body and cornea as part of an investigation into the mechanism of glucocorticoid-induced glaucoma. Cortisol is readily converted to the inactive metabolite cortisone by these eye tissues indicating the presence of an 11beta-oxidoreductase system. This reaction is reversible with cortisone being converted to cortisol in the presence of appropriate cofactor. However, due to the absence of a (or as yet undetectable) cortisol-A-ring-reductase system (rate-limiting reaction) the steroid is not irreversibly metabolized to biologically inactive compounds. The 11beta-oxidoreductase system readily converts other C21-11beta-hydroxysteroids, such as corticosterone, to its appropriate C21-11-ketosteroid (11-dehydrocorticosterone). Some C21-steroids lacking the 11-hydroxyl group (11-deoxycortisol, 11-deoxycorticosterone) remain virtually unmetabolized (exception to this was found with progesterone). Evidence of a C21-steroid A-ring reductase system was found only when cortisone and progesterone were used as substrates. However, testosterone a C19 steroid was converted to clearly identifiable A-ring reduced and 17beta-and 3alpha(beta)-oxidoreduced metabolites, thus indicating the presence of testosterone A-ring reductase, 17beta-and 3alpha(beta)-oxidoreductase systems in the eye tissues studied. The presence of a steroid 5alpha(beta)-reductase for some steroids but not for cortisol indicates a distinct substrate specificity for this enzyme system in the eye tissues."} {"id": "PMID:1254412", "title": "Components of vitreous-soluble proteins: effect of hyperoxia and age.", "content": "In young puppies, the retina, which is incompletely vascularized at birth becomes fully vascularized at approximately four weeks of age. During this period of vessel growth the total content of vitreous-soluble protein was found closely associated with the rate of retinal vessel growth. As vascularization progressed toward completion, the protein originally present at birth decreased to a negligible or undetected amount. Intravitreal neovascularization was produced in young puppies by exposure to 85 per cent oxygen for four days, then removal to room air. This form of neovascularization resembles closely that observed in human proliferative diabetic retinopathy. The oxygen treatment, which initially produced retinal capillary closure, then neovascularization, was associated with a retention of vitreous-soluble protein at a high level for several days. The results raise the possibility that the vitreous protein(s) may be fundamentally involved in the process of normal vascularization of the retina and in retinal neovascularization.", "contents": "Components of vitreous-soluble proteins: effect of hyperoxia and age. In young puppies, the retina, which is incompletely vascularized at birth becomes fully vascularized at approximately four weeks of age. During this period of vessel growth the total content of vitreous-soluble protein was found closely associated with the rate of retinal vessel growth. As vascularization progressed toward completion, the protein originally present at birth decreased to a negligible or undetected amount. Intravitreal neovascularization was produced in young puppies by exposure to 85 per cent oxygen for four days, then removal to room air. This form of neovascularization resembles closely that observed in human proliferative diabetic retinopathy. The oxygen treatment, which initially produced retinal capillary closure, then neovascularization, was associated with a retention of vitreous-soluble protein at a high level for several days. The results raise the possibility that the vitreous protein(s) may be fundamentally involved in the process of normal vascularization of the retina and in retinal neovascularization."} {"id": "PMID:1254413", "title": "Essential fatty acid deficiency and renewal of rod outer segments in the albino rat.", "content": "Biochemical studies in albino rats fed a lab chow diet (control) showed a 9 to 10 day turnover time for rhodopsin in rod photoreceptor membranes, whereas the turnover time in animals raised on a fat-free diet (experimental) was not easily measurable. The number of phagosomes in the pigment epithelium of the control group was three times that found in the experimetals. These studies support earlier autoradiographic data which suggested that the renewal of new photoreceptor discs in the rat retina is controlled by the availability of polyunsaturated fatty acids.", "contents": "Essential fatty acid deficiency and renewal of rod outer segments in the albino rat. Biochemical studies in albino rats fed a lab chow diet (control) showed a 9 to 10 day turnover time for rhodopsin in rod photoreceptor membranes, whereas the turnover time in animals raised on a fat-free diet (experimental) was not easily measurable. The number of phagosomes in the pigment epithelium of the control group was three times that found in the experimetals. These studies support earlier autoradiographic data which suggested that the renewal of new photoreceptor discs in the rat retina is controlled by the availability of polyunsaturated fatty acids."} {"id": "PMID:1254416", "title": "Bradykinin-induced changes in caliber of portal vein during splanchnic angiography.", "content": "The caliber of the portal vein was investigated in two groups of patients subjected to celiac and mesenteric angiography. In one group, 10 patients (the controls) two angiographic series were performed without giving any pharmacon but the contrast medium. In the other group, 20 patients, also two angiographic series were performed but bradykinin 10 mug was given in the superior mesenteric artery before the second series. Injection of bradykinin resulted in a dilation of the portal vein in 18 of 20 patients, while there was no change in portal caliber in the controls.", "contents": "Bradykinin-induced changes in caliber of portal vein during splanchnic angiography. The caliber of the portal vein was investigated in two groups of patients subjected to celiac and mesenteric angiography. In one group, 10 patients (the controls) two angiographic series were performed without giving any pharmacon but the contrast medium. In the other group, 20 patients, also two angiographic series were performed but bradykinin 10 mug was given in the superior mesenteric artery before the second series. Injection of bradykinin resulted in a dilation of the portal vein in 18 of 20 patients, while there was no change in portal caliber in the controls."} {"id": "PMID:1254417", "title": "Effect of bradykinin on portal pressure and protal caliber in the dog. An experimental angiographic study.", "content": "Portal pressure and caliber of the portal vein was examined in dogs after bradykinin injection (0.5 mug/kg bodyweitght) into the superior mesenteric artery. Ten experiments were performed. The portal pressure rose from a mean of 10.4 cm H2O to a mean of 21.2 cm H2O after bradykinin injection. The portal vein was dilated in 8 of the 10 experiments. Also the portal circulation time was calculated and decreased after bradykinin injection. Thus, because of the increase in portal pressure and increase in portal circulation care should be exercised when injecting bradykinin into the superior mesenteric artery in patients with portal hypertension and imminent bleeding from oesophageal varices.", "contents": "Effect of bradykinin on portal pressure and protal caliber in the dog. An experimental angiographic study. Portal pressure and caliber of the portal vein was examined in dogs after bradykinin injection (0.5 mug/kg bodyweitght) into the superior mesenteric artery. Ten experiments were performed. The portal pressure rose from a mean of 10.4 cm H2O to a mean of 21.2 cm H2O after bradykinin injection. The portal vein was dilated in 8 of the 10 experiments. Also the portal circulation time was calculated and decreased after bradykinin injection. Thus, because of the increase in portal pressure and increase in portal circulation care should be exercised when injecting bradykinin into the superior mesenteric artery in patients with portal hypertension and imminent bleeding from oesophageal varices."} {"id": "PMID:1254418", "title": "Gallium-67 citrate in cerebral infarction.", "content": "Cerebral scans were obtained on 30 \"stroke\" patients first with 99mTc pertechnetate and subsequently with 67Ga citrate. Of the 26 patients with abnormal 99mTc static scans, 17 (65%) showed the same abnormality in gallium citrate scans also. In 4 patients with positive technetium flow studies but negative static scans, no abnormality was seen in the scans obtained after gallium citrate injection. In none of the patients was the relative concentration of radioactivity in the lesion greater in the gallium image than in the technetium image. This study proves the nonspecificity of gallium citrate and thus its inability to differentiate cerebral tumor from cerebral infarction just on the basis of localization of gallium.", "contents": "Gallium-67 citrate in cerebral infarction. Cerebral scans were obtained on 30 \"stroke\" patients first with 99mTc pertechnetate and subsequently with 67Ga citrate. Of the 26 patients with abnormal 99mTc static scans, 17 (65%) showed the same abnormality in gallium citrate scans also. In 4 patients with positive technetium flow studies but negative static scans, no abnormality was seen in the scans obtained after gallium citrate injection. In none of the patients was the relative concentration of radioactivity in the lesion greater in the gallium image than in the technetium image. This study proves the nonspecificity of gallium citrate and thus its inability to differentiate cerebral tumor from cerebral infarction just on the basis of localization of gallium."} {"id": "PMID:1254419", "title": "Velocity of left ventricular wall motion determined by fluoroscopic videodensitometry. A noninvasive method for evaluating myocardial contractile state.", "content": "Videodensitometry of the margins of the fluoroscopic image of the left ventricle (LV) was used to evaluate LV wall motion and differentiation of the wall motion signal reflected velocity of LV contraction (dV/dt) during various inotropic interventions in six anesthetized dogs. During these interventions heart rate, afterload and preload were maintained constant. Alterations in dV/dt were similar to changes in simultaneously measured LV peak dP/dt and the quotient of dP/dt and developed LV pressure, two widely accepted parameters of LV contractile state. Wide variations in preload and afterload caused no significant changes in dV/dt. Thus, the current study indicates that fluoroscopic videodensitometry provides a specific and reliable noninvasive method for evaluating LV contractile state.", "contents": "Velocity of left ventricular wall motion determined by fluoroscopic videodensitometry. A noninvasive method for evaluating myocardial contractile state. Videodensitometry of the margins of the fluoroscopic image of the left ventricle (LV) was used to evaluate LV wall motion and differentiation of the wall motion signal reflected velocity of LV contraction (dV/dt) during various inotropic interventions in six anesthetized dogs. During these interventions heart rate, afterload and preload were maintained constant. Alterations in dV/dt were similar to changes in simultaneously measured LV peak dP/dt and the quotient of dP/dt and developed LV pressure, two widely accepted parameters of LV contractile state. Wide variations in preload and afterload caused no significant changes in dV/dt. Thus, the current study indicates that fluoroscopic videodensitometry provides a specific and reliable noninvasive method for evaluating LV contractile state."} {"id": "PMID:1254420", "title": "Saturation kinetics of iopanoate in dogs with an intact enterohepatic circulation. Before and after phenobarbital induction.", "content": "Capacity-limited elimination of sodium iopanoate and a reproducible apparent transport maximum (Tm) were demonstrated in nonoperated dogs having an intact enterohepatic circulation and normal endogenous bile salt pool. Using a multiple infusion technique, estimation of apparent Tm of iopanoate in the liver was possible without sampling either bile or urine. Values obtained for apparent Tm of iopanoate in dogs with normal bile salt pool were similar to those obtained in studies of dogs with chronic bile fistulas. Use of this technique in 4 dogs demonstrated that pretreatment with phenobarbital significantly increases apparent Tm of iopanoate.", "contents": "Saturation kinetics of iopanoate in dogs with an intact enterohepatic circulation. Before and after phenobarbital induction. Capacity-limited elimination of sodium iopanoate and a reproducible apparent transport maximum (Tm) were demonstrated in nonoperated dogs having an intact enterohepatic circulation and normal endogenous bile salt pool. Using a multiple infusion technique, estimation of apparent Tm of iopanoate in the liver was possible without sampling either bile or urine. Values obtained for apparent Tm of iopanoate in dogs with normal bile salt pool were similar to those obtained in studies of dogs with chronic bile fistulas. Use of this technique in 4 dogs demonstrated that pretreatment with phenobarbital significantly increases apparent Tm of iopanoate."} {"id": "PMID:1254425", "title": "Some contractile and electrophysiologic properties of the periurethral striated muscle of the cat.", "content": "Evidence for differences between the periurethral striated muscle and external anal sphincter of the cat is provided by measurement of the contractile properties in situ and in vitro and the electrophysiologic properties in vitro. In the periurethral striated muscle, the contractile pressure response was faster, d-tubocurarine sensitivity was greater, d-tubocurarine blockade had a shorter duration, and fatigue was faster but not uniquely fast as compared with results for the external anal sphincter. These results suggest that the periurethral striated muscle has similar characteristics to certain fast twitch muscles. Effect of succinylcholine on the periurethral striated muscle and external anal sphincter was similar. Miniature end-plate potentials had large amplitudes which appeared to be correlated to the small diameter of the periurethral striated muscle fibers. Since only focally distributed miniature end-plate potentials could be found, true physiologically slow muscle fibers were absent.", "contents": "Some contractile and electrophysiologic properties of the periurethral striated muscle of the cat. Evidence for differences between the periurethral striated muscle and external anal sphincter of the cat is provided by measurement of the contractile properties in situ and in vitro and the electrophysiologic properties in vitro. In the periurethral striated muscle, the contractile pressure response was faster, d-tubocurarine sensitivity was greater, d-tubocurarine blockade had a shorter duration, and fatigue was faster but not uniquely fast as compared with results for the external anal sphincter. These results suggest that the periurethral striated muscle has similar characteristics to certain fast twitch muscles. Effect of succinylcholine on the periurethral striated muscle and external anal sphincter was similar. Miniature end-plate potentials had large amplitudes which appeared to be correlated to the small diameter of the periurethral striated muscle fibers. Since only focally distributed miniature end-plate potentials could be found, true physiologically slow muscle fibers were absent."} {"id": "PMID:1254426", "title": "Urinary cytology automation. Preliminary studies with acridine orange stain and flow-through cytofluorometry.", "content": "Preliminary results are reported in an ongoing program to develop automated cytologic examinations for the detection of bladder cancer from exfoliated urinary epithelium. A metachromatic fluorescent dye, acridine orange, was used to stain the cells in suspension in such a way that their nuclei (DNA) fluoresced green in blue light, and their cytoplasm (chiefly RNA) fluoresced red. The intensities of green and red fluorescence per cell were measured for up to 5000 cells per sample by a flow-through cytofluorometer, and differences were found between cell types that served to identify bladder epithelial cells, leukocytes, squamous cells, and other particulates. Benign and malignant bladder epithelial cells differed principally in their cytoplasmic RNA staining intensity, and methods are discussed for amplifying this and other differences that may be of diagnostic value in an automated instrumental system.", "contents": "Urinary cytology automation. Preliminary studies with acridine orange stain and flow-through cytofluorometry. Preliminary results are reported in an ongoing program to develop automated cytologic examinations for the detection of bladder cancer from exfoliated urinary epithelium. A metachromatic fluorescent dye, acridine orange, was used to stain the cells in suspension in such a way that their nuclei (DNA) fluoresced green in blue light, and their cytoplasm (chiefly RNA) fluoresced red. The intensities of green and red fluorescence per cell were measured for up to 5000 cells per sample by a flow-through cytofluorometer, and differences were found between cell types that served to identify bladder epithelial cells, leukocytes, squamous cells, and other particulates. Benign and malignant bladder epithelial cells differed principally in their cytoplasmic RNA staining intensity, and methods are discussed for amplifying this and other differences that may be of diagnostic value in an automated instrumental system."} {"id": "PMID:1254427", "title": "Ureteral function. III. The catheter and the geometry of the ureter.", "content": "The geometry of a canine ureter with and without the presence of an indwelling catheter has been studied after in vivo freezing and sectioning. Changes in ureteral cross-section were observed as catheter size was increased from about 2 Fr. through 6 Fr. using a new microphotographic procedure. These preliminary results indicate direct contact between the ureteral wall and catheter during ureteral contraction, relaxation, and inactivity. In the region of a urine bolus, an open lumen could be clearly observed. The shape of the lumen appears to depend on the bolus volume, the size of the catheter, and local muscular characteristics of the ureteral wall. In the absence of a catheter, the lumen appears to vary between a totally collapsed configuration and an almost circular shape.", "contents": "Ureteral function. III. The catheter and the geometry of the ureter. The geometry of a canine ureter with and without the presence of an indwelling catheter has been studied after in vivo freezing and sectioning. Changes in ureteral cross-section were observed as catheter size was increased from about 2 Fr. through 6 Fr. using a new microphotographic procedure. These preliminary results indicate direct contact between the ureteral wall and catheter during ureteral contraction, relaxation, and inactivity. In the region of a urine bolus, an open lumen could be clearly observed. The shape of the lumen appears to depend on the bolus volume, the size of the catheter, and local muscular characteristics of the ureteral wall. In the absence of a catheter, the lumen appears to vary between a totally collapsed configuration and an almost circular shape."} {"id": "PMID:1254421", "title": "The role of serum albumin in the hepatic excretion of iodipamide.", "content": "The contrast agent for biliary tract visualization, iodipamide, is strongly bound to serum albumin. The relationship between the affinity of the contrast agent for albumin and its preferential uptake and excretion by the liver has been unclear. The role of serum albumin on hepatic uptake and excretion of iodipamide therefore was investigated on the isolated perfused rabbit liver. With the perfusate containing fully reconstituted rabbit plasma protein or 3.5 g/100 ml rabbit albumin alone, the iodipamide excretion is initially extremely slow. It then increases gradually to about 6 mug/gm liver per min by 60 minutes and thereafter remains constant. The half-time of transfer to the bile is about 130 min. Without albumin in the perfusate the initial clearance rate of iodipamide is rapid, with half-time transfer to the bile of about 40 min. Rabbit serum globulins have no effect on iodipamide excretion. Thus, binding of iodipamide to albumin retards the transfer of iodipamide from plasma to the bile, probably due to competition between albumin and the anion binding protein of the liver.", "contents": "The role of serum albumin in the hepatic excretion of iodipamide. The contrast agent for biliary tract visualization, iodipamide, is strongly bound to serum albumin. The relationship between the affinity of the contrast agent for albumin and its preferential uptake and excretion by the liver has been unclear. The role of serum albumin on hepatic uptake and excretion of iodipamide therefore was investigated on the isolated perfused rabbit liver. With the perfusate containing fully reconstituted rabbit plasma protein or 3.5 g/100 ml rabbit albumin alone, the iodipamide excretion is initially extremely slow. It then increases gradually to about 6 mug/gm liver per min by 60 minutes and thereafter remains constant. The half-time of transfer to the bile is about 130 min. Without albumin in the perfusate the initial clearance rate of iodipamide is rapid, with half-time transfer to the bile of about 40 min. Rabbit serum globulins have no effect on iodipamide excretion. Thus, binding of iodipamide to albumin retards the transfer of iodipamide from plasma to the bile, probably due to competition between albumin and the anion binding protein of the liver."} {"id": "PMID:1254428", "title": "Dissolution of struvite urinary stones. Experimental studies in vitro.", "content": "Previous studies from our laboratory have shown that struvite crystals form primarily as a result of urease-induced alkalinity and supersaturation. In vitro perfusion of struvite crystals with undersaturated urine caused crystal dissolution. The investigations reported herein demonstrate complete dissolution of human struvite urinary stones during 6 weeks of perfusion in vitro with undersaturated human urine. Human hydroxyapatite stones perfused similarly underwent only slight dissolution. A glycoprotein precipitated as the stones dissolved; the pathogenic significance of the glycoprotein is unknown.", "contents": "Dissolution of struvite urinary stones. Experimental studies in vitro. Previous studies from our laboratory have shown that struvite crystals form primarily as a result of urease-induced alkalinity and supersaturation. In vitro perfusion of struvite crystals with undersaturated urine caused crystal dissolution. The investigations reported herein demonstrate complete dissolution of human struvite urinary stones during 6 weeks of perfusion in vitro with undersaturated human urine. Human hydroxyapatite stones perfused similarly underwent only slight dissolution. A glycoprotein precipitated as the stones dissolved; the pathogenic significance of the glycoprotein is unknown."} {"id": "PMID:1254422", "title": "The location of increased resistance to portal blood flow in obstructive jaundice.", "content": "The simultaneous measurement of wedged hepatic venous pressure and portal venous pressure at 11 and 28 days following common bile duct and intrahepatic bile duct obstruction reveals a significant elevation of the portal pressure at 28 days which is due primarily to increased presinusoidal resistance to portal blood flow. Portal venograms performed prior to sacrifice revealed moderate narrowing of the portal vein radicles and delayed emptying at 11 days and severe morphological alterations at 28 days. These results confirm the findings of other investigators and help to explain why the hemodynamic alterations occur so rapidly in obstructive jaundice, well before the development of significant biliary cirrhosis.", "contents": "The location of increased resistance to portal blood flow in obstructive jaundice. The simultaneous measurement of wedged hepatic venous pressure and portal venous pressure at 11 and 28 days following common bile duct and intrahepatic bile duct obstruction reveals a significant elevation of the portal pressure at 28 days which is due primarily to increased presinusoidal resistance to portal blood flow. Portal venograms performed prior to sacrifice revealed moderate narrowing of the portal vein radicles and delayed emptying at 11 days and severe morphological alterations at 28 days. These results confirm the findings of other investigators and help to explain why the hemodynamic alterations occur so rapidly in obstructive jaundice, well before the development of significant biliary cirrhosis."} {"id": "PMID:1254429", "title": "Study on the efficiency of electric stimulation of the pelvic floor.", "content": "The continuous electric stimulation of the anal sphincter leads to the onset of a very quick fatigue of the muscle, with a progressive decrease of the amplitude of contraction after 15 min of stimulation. Under the same experimental conditions intermittent stimulation leads to a sustained contraction amplitude. Ts and Tr combinations that can give efficiency rates of contraction above 80 per cent were defined. The results of this study could be applied when intermittent electric stimulation of the pelvic floor is indicated for the treatment of anal or urinary incontinence.", "contents": "Study on the efficiency of electric stimulation of the pelvic floor. The continuous electric stimulation of the anal sphincter leads to the onset of a very quick fatigue of the muscle, with a progressive decrease of the amplitude of contraction after 15 min of stimulation. Under the same experimental conditions intermittent stimulation leads to a sustained contraction amplitude. Ts and Tr combinations that can give efficiency rates of contraction above 80 per cent were defined. The results of this study could be applied when intermittent electric stimulation of the pelvic floor is indicated for the treatment of anal or urinary incontinence."} {"id": "PMID:1254430", "title": "New studies with intravasal devices. The soft valve.", "content": "In contrast to the results that were obtained with rigid ended prosthetic devices, effective sperm transport occurred for prolonged periods of time through the IITRI Vas-Valve, which had soft silicone rubber flexible end tubes when implanted in the vasa deferentia of dogs. Such transport could be halted by device occlusion with stainless steel springs or with shuttle stem valves. Opening the devices resulted once more in the passage of spermatozoa as well as the production of offspring, indicating that these devices have the potential for being useful as a human male contraceptive method. More research needs to be performed to determine why there is an over-all decrease in sperm output after device implantation and to evaluate and adverse side effects of such devices. The presence of Dacron velour-covered suture rings on the devices permitted effective tissue ingrowth and prevented leakage or recanalization in all cases.", "contents": "New studies with intravasal devices. The soft valve. In contrast to the results that were obtained with rigid ended prosthetic devices, effective sperm transport occurred for prolonged periods of time through the IITRI Vas-Valve, which had soft silicone rubber flexible end tubes when implanted in the vasa deferentia of dogs. Such transport could be halted by device occlusion with stainless steel springs or with shuttle stem valves. Opening the devices resulted once more in the passage of spermatozoa as well as the production of offspring, indicating that these devices have the potential for being useful as a human male contraceptive method. More research needs to be performed to determine why there is an over-all decrease in sperm output after device implantation and to evaluate and adverse side effects of such devices. The presence of Dacron velour-covered suture rings on the devices permitted effective tissue ingrowth and prevented leakage or recanalization in all cases."} {"id": "PMID:1254431", "title": "The generation of formaldehyde from methenamine. Effect of urinary flow and residual volume.", "content": "The antimicrobial effect of methenamine in urine is dependent upon: (i) the rate of generation of formaldehyde; (ii) the concentration of formaldehyde achieved; and (iii) the duration of bacterial exposure to formaldehyde. Studies utilizing an in vitro model which simulates the dynamics of the urinary tract showed that bacteriostatic concentrations of formaldehyde (greater than or equal to 25 mug per ml) were obtained from attainable concentrations of methenamine at urine pH 5.7 to 5.85. Reduced urinary flow rates and large residual volumes increased formaldehyde concentrations and would appear to provide prolonged bacterial exposure to the formaldehyde.", "contents": "The generation of formaldehyde from methenamine. Effect of urinary flow and residual volume. The antimicrobial effect of methenamine in urine is dependent upon: (i) the rate of generation of formaldehyde; (ii) the concentration of formaldehyde achieved; and (iii) the duration of bacterial exposure to formaldehyde. Studies utilizing an in vitro model which simulates the dynamics of the urinary tract showed that bacteriostatic concentrations of formaldehyde (greater than or equal to 25 mug per ml) were obtained from attainable concentrations of methenamine at urine pH 5.7 to 5.85. Reduced urinary flow rates and large residual volumes increased formaldehyde concentrations and would appear to provide prolonged bacterial exposure to the formaldehyde."} {"id": "PMID:1254432", "title": "The ureterovesical junction of the rabbit.", "content": "Twelve New Zealand rabbits were studied for ureterovesical reflux. Dissections revealed the intramural ureter and ureterovesical junction to follow an upward and medial course, unlike the course observed in man. This course could not be altered or distorted by dissection of the bladder base or ureter, by freeing the urether retroperitoneally, or by changing the position of the animal.", "contents": "The ureterovesical junction of the rabbit. Twelve New Zealand rabbits were studied for ureterovesical reflux. Dissections revealed the intramural ureter and ureterovesical junction to follow an upward and medial course, unlike the course observed in man. This course could not be altered or distorted by dissection of the bladder base or ureter, by freeing the urether retroperitoneally, or by changing the position of the animal."} {"id": "PMID:1254434", "title": "Alterations in the red blood cell membrane and the effect of vitamin E on osmotic fragility in beta-thalassemia major.", "content": "Red blood cell membranes from patients with beta-thalassemia major and intermedia had an average of 25% less sialic acids, and a 50% decrease in titratable SH groups, as compared with normal controls. Membranes from 12 of 13 splenectomized patients were less dense and could be clearly distinguished from normal membranes on a sucrose linear density gradient, indicating a change in lipid-to-protein ratio. The impaired osmotic fragility of thalassemic erythrocytes almost returned to normal following administration of vitamin E, a potent antioxidant, in a daily dose of 750 IU for three to six months. These observations provide more evidence that membrane properties of thalassemic red blood cells differ from those of normal erythrocytes, the difference being due, in part, to increased oxidative stress.", "contents": "Alterations in the red blood cell membrane and the effect of vitamin E on osmotic fragility in beta-thalassemia major. Red blood cell membranes from patients with beta-thalassemia major and intermedia had an average of 25% less sialic acids, and a 50% decrease in titratable SH groups, as compared with normal controls. Membranes from 12 of 13 splenectomized patients were less dense and could be clearly distinguished from normal membranes on a sucrose linear density gradient, indicating a change in lipid-to-protein ratio. The impaired osmotic fragility of thalassemic erythrocytes almost returned to normal following administration of vitamin E, a potent antioxidant, in a daily dose of 750 IU for three to six months. These observations provide more evidence that membrane properties of thalassemic red blood cells differ from those of normal erythrocytes, the difference being due, in part, to increased oxidative stress."} {"id": "PMID:1254435", "title": "Mitral stenosis with pulmonary hypertension. Long-term results after mitral valvotomy.", "content": "Ten patients suffering from tight mitral stenosis with severe pulmonary hypertension were operated on and followed up for one to nine years after operation. There was no operative or postoperative mortality. Postoperative hemodynamic studies were performed on seven of the 10 patients. One patient was evaluated twice--one month and seven months after surgery. The condition of all patients improved after operation and regression of severe to extreme pulmonary hypertension was documented in the seven patients on whom the hemodynamic studies were repeated. Hemodynamic and clinical improvement was greatest in young patients with a shorter duration of disease and a normal sinus rhythm prior to operation. The results indicate that a severe degree of pulmonary vascular resistance in mitral stenosis is largely reversible, provided that the obstruction is adequately relieved.", "contents": "Mitral stenosis with pulmonary hypertension. Long-term results after mitral valvotomy. Ten patients suffering from tight mitral stenosis with severe pulmonary hypertension were operated on and followed up for one to nine years after operation. There was no operative or postoperative mortality. Postoperative hemodynamic studies were performed on seven of the 10 patients. One patient was evaluated twice--one month and seven months after surgery. The condition of all patients improved after operation and regression of severe to extreme pulmonary hypertension was documented in the seven patients on whom the hemodynamic studies were repeated. Hemodynamic and clinical improvement was greatest in young patients with a shorter duration of disease and a normal sinus rhythm prior to operation. The results indicate that a severe degree of pulmonary vascular resistance in mitral stenosis is largely reversible, provided that the obstruction is adequately relieved."} {"id": "PMID:1254436", "title": "A prospective clinicopathological study of 1,108 cases of antenatal fetal death.", "content": "A prospective clinicopathological study of antenatal fetal death (AFD) showed that in most cases multiple factors were involved and that in about 70% of the cases maternal diseases were responsible for AFD. The main causes of AFD appeared to be toxemia of pregnancy, various diabetic conditions of the mother (60% of the cases), and blood group incompatibility. Closer and more frequent supervision of pregnant women attending the antenatal clinics will enable earlier detection of maternal disease, and thus may be important in preventing AFD. A simplified oral glucose tolerance test for early detection of diabetes should be performed during pregnancy. In every case of AFD, the placenta and the fetus should be sent for pathological examination.", "contents": "A prospective clinicopathological study of 1,108 cases of antenatal fetal death. A prospective clinicopathological study of antenatal fetal death (AFD) showed that in most cases multiple factors were involved and that in about 70% of the cases maternal diseases were responsible for AFD. The main causes of AFD appeared to be toxemia of pregnancy, various diabetic conditions of the mother (60% of the cases), and blood group incompatibility. Closer and more frequent supervision of pregnant women attending the antenatal clinics will enable earlier detection of maternal disease, and thus may be important in preventing AFD. A simplified oral glucose tolerance test for early detection of diabetes should be performed during pregnancy. In every case of AFD, the placenta and the fetus should be sent for pathological examination."} {"id": "PMID:1254437", "title": "Some physical properties of the Haifa occlusive dressing for burns.", "content": "In order to evaluate some of the physical properties of the Haifa Occlusive Dressing, which is in use in our Department, temperature, moisture and the transfer of gases were measured. The Haifa Occlusive Dressing does not significantly raise the temperature of the covered burn, nor does it hinder the diffusion of gases, even when wet. Measurements taken from a patient suffering from a deep second degree burn showed that the amount of secretion over a 9-h period was 270 cm3 and the rate of secretion/unit area was 0.0125 cm/h.", "contents": "Some physical properties of the Haifa occlusive dressing for burns. In order to evaluate some of the physical properties of the Haifa Occlusive Dressing, which is in use in our Department, temperature, moisture and the transfer of gases were measured. The Haifa Occlusive Dressing does not significantly raise the temperature of the covered burn, nor does it hinder the diffusion of gases, even when wet. Measurements taken from a patient suffering from a deep second degree burn showed that the amount of secretion over a 9-h period was 270 cm3 and the rate of secretion/unit area was 0.0125 cm/h."} {"id": "PMID:1254471", "title": "[Protection against light in normal and diseased skin].", "content": "At the beginning of the holiday season dermatologists are regularily confronted with questions of light protection. Based on these questions and the respective replies the above subject is discussed. The following differentiation has to be considered: Cosmetical light protection. Light protection in case of pathological sensitivity to light. Light protection in case of light dermatoses. Besides a few exceptions (e.g. in the therapy of porphyria and similar diseases) light protection is a physical, absorptive process, i.e. a part of the UV rays is absorbed before reaching the skin. In abnormal light sensitivity, the UVA with longer wave lengths plays a part too, whereas for \"normal skin\" UVB with medium wave lengths is responsible for the light induced reactions. Details concerning selection, application, and effect of light protecting measurements are discussed.", "contents": "[Protection against light in normal and diseased skin]. At the beginning of the holiday season dermatologists are regularily confronted with questions of light protection. Based on these questions and the respective replies the above subject is discussed. The following differentiation has to be considered: Cosmetical light protection. Light protection in case of pathological sensitivity to light. Light protection in case of light dermatoses. Besides a few exceptions (e.g. in the therapy of porphyria and similar diseases) light protection is a physical, absorptive process, i.e. a part of the UV rays is absorbed before reaching the skin. In abnormal light sensitivity, the UVA with longer wave lengths plays a part too, whereas for \"normal skin\" UVB with medium wave lengths is responsible for the light induced reactions. Details concerning selection, application, and effect of light protecting measurements are discussed."} {"id": "PMID:1254472", "title": "[Nodular cutaneous amyloidosis. Clinical, histopathological and ultrastructural findings].", "content": "A case of nodular amyloidosis cutis of the face with minimal deposits of amyloid in the rectum is reported with respect to clinical, histopathological, and ultrastructural findings. A discussion of the problem of systematization in nodular amyloidoses is included. By electron microscopy, the principal similarity of the ultrastructure of amyloid is stressed again. Amyloid in this case of nodular amyloidosis cutis is thought to be synthesized by plasma cells which are found especially in the growing peripheral parts of the tumors. Fibroblasts with extremely dilated endoplasmic reticulum are almost totally surrounded by the fibrillar masses of amyloid within the tumor. Unusual spindle-formed cisternae of Golgi bodies containing oriented coarse fibrils are found in the fibroblasts. They are thought to represent a disturbance of the secretion of tropocollagen to the interstitium due to the surrounding amyloid masses.", "contents": "[Nodular cutaneous amyloidosis. Clinical, histopathological and ultrastructural findings]. A case of nodular amyloidosis cutis of the face with minimal deposits of amyloid in the rectum is reported with respect to clinical, histopathological, and ultrastructural findings. A discussion of the problem of systematization in nodular amyloidoses is included. By electron microscopy, the principal similarity of the ultrastructure of amyloid is stressed again. Amyloid in this case of nodular amyloidosis cutis is thought to be synthesized by plasma cells which are found especially in the growing peripheral parts of the tumors. Fibroblasts with extremely dilated endoplasmic reticulum are almost totally surrounded by the fibrillar masses of amyloid within the tumor. Unusual spindle-formed cisternae of Golgi bodies containing oriented coarse fibrils are found in the fibroblasts. They are thought to represent a disturbance of the secretion of tropocollagen to the interstitium due to the surrounding amyloid masses."} {"id": "PMID:1254473", "title": "[Diagnostic possibilities using RAST. Correlation with three various skin extracts].", "content": "The correlation between RAST and three different commercial extracts referred to allergen and commercial gives a review of the reliability of skin tests (up to 25% false results). The question whether both RAST-discs for house dust and house dust mite have to be used is discussed. The common allergens of house dust mites and the rarer allergens of cats and guinea-pigs are emphasized.", "contents": "[Diagnostic possibilities using RAST. Correlation with three various skin extracts]. The correlation between RAST and three different commercial extracts referred to allergen and commercial gives a review of the reliability of skin tests (up to 25% false results). The question whether both RAST-discs for house dust and house dust mite have to be used is discussed. The common allergens of house dust mites and the rarer allergens of cats and guinea-pigs are emphasized."} {"id": "PMID:1254510", "title": "Veterinary medical manpower: supply-demand projections to 2020.", "content": "A supply projection model to estimate the number of veterinarians available through the year 2020 was developed. When projected available manpower was compared with the need for veterinary medical services, as estimated in a National Academy of Science study, a net shortage was indicated in each year between 1976 and 2020. The manpower supply available if 3 additional veterinary colleges were developed in the United States was also estimated. It was concluded that, even with the additional output of these colleges, the supply of veterinarians will not keep pace with future needs for veterinary services.", "contents": "Veterinary medical manpower: supply-demand projections to 2020. A supply projection model to estimate the number of veterinarians available through the year 2020 was developed. When projected available manpower was compared with the need for veterinary medical services, as estimated in a National Academy of Science study, a net shortage was indicated in each year between 1976 and 2020. The manpower supply available if 3 additional veterinary colleges were developed in the United States was also estimated. It was concluded that, even with the additional output of these colleges, the supply of veterinarians will not keep pace with future needs for veterinary services."} {"id": "PMID:1254515", "title": "Squamous cell carcinoma in dogs.", "content": "In a review of neoplasm registry records at Kansas State University (1961 through 1971), 112 squamous cell carcinomas were reported in 38 breeds of dogs, representing 3.2% of 3,481 neoplasms recorded. Mean age of the affected dogs was 8.3 years. Metastases occurred in 7 dogs. The tumors were removed surgically for biopsy in 104 dogs, 8 of which then had recurrences and required further surgery. The oral cavity was the principal site (18%) of squamous cell carcinomas in the 112 dogs.", "contents": "Squamous cell carcinoma in dogs. In a review of neoplasm registry records at Kansas State University (1961 through 1971), 112 squamous cell carcinomas were reported in 38 breeds of dogs, representing 3.2% of 3,481 neoplasms recorded. Mean age of the affected dogs was 8.3 years. Metastases occurred in 7 dogs. The tumors were removed surgically for biopsy in 104 dogs, 8 of which then had recurrences and required further surgery. The oral cavity was the principal site (18%) of squamous cell carcinomas in the 112 dogs."} {"id": "PMID:1254517", "title": "Patent ductus arteriosus in the dog: characteristics of occurrence and results of surgery in one hundred consecutive cases.", "content": "The results of surgical repair of patent ductus arteriosus (100 dogs) were compared with the results of nonsurgical treatment of this defect (14 dogs). The death rate for dogs surgically treated was 8%, with 2 deaths at surgery and 6 late postoperative deaths. In the nonsurgical group, 64% died within one year of the examination. The increased survival rate for the surgically treated group was significant ( P less than 0.001). Surgical death rate was high for dogs more than 2 years old and weighing more than 23 kg. It was concluded that surgery is the preferred method of treatment and that early surgery increases the survival rate of dogs with patent ductus arteriosus, compared with the survival rate for older, heavier dogs with the defect.", "contents": "Patent ductus arteriosus in the dog: characteristics of occurrence and results of surgery in one hundred consecutive cases. The results of surgical repair of patent ductus arteriosus (100 dogs) were compared with the results of nonsurgical treatment of this defect (14 dogs). The death rate for dogs surgically treated was 8%, with 2 deaths at surgery and 6 late postoperative deaths. In the nonsurgical group, 64% died within one year of the examination. The increased survival rate for the surgically treated group was significant ( P less than 0.001). Surgical death rate was high for dogs more than 2 years old and weighing more than 23 kg. It was concluded that surgery is the preferred method of treatment and that early surgery increases the survival rate of dogs with patent ductus arteriosus, compared with the survival rate for older, heavier dogs with the defect."} {"id": "PMID:1254518", "title": "Disappearance of spermatoza from the ejaculates of vasectomized dogs.", "content": "Ejaculates of bilaterally vasectomized dogs contained spermatozoa as long as 21 days after vasectomy, indicating that spermatozoa in the canine ejaculate originated from both the epididymides and the vasa deferentia, not from the epididymides alone.", "contents": "Disappearance of spermatoza from the ejaculates of vasectomized dogs. Ejaculates of bilaterally vasectomized dogs contained spermatozoa as long as 21 days after vasectomy, indicating that spermatozoa in the canine ejaculate originated from both the epididymides and the vasa deferentia, not from the epididymides alone."} {"id": "PMID:1254519", "title": "Amphetamine poisoning in dogs.", "content": "Amphetamine intoxication in dogs referred to the Veterinary Diagnostic Laboratory or the Veterinary Hospital of the University of Minnesota was characterized by excitement, agitation, hyperthermia, and convulsive episodes that could be confused with other convulsant poisonings. Extraction procedures on stomach contents or urine enabled indentification of the drug, using ultraviolet spectrophotometry.", "contents": "Amphetamine poisoning in dogs. Amphetamine intoxication in dogs referred to the Veterinary Diagnostic Laboratory or the Veterinary Hospital of the University of Minnesota was characterized by excitement, agitation, hyperthermia, and convulsive episodes that could be confused with other convulsant poisonings. Extraction procedures on stomach contents or urine enabled indentification of the drug, using ultraviolet spectrophotometry."} {"id": "PMID:1254524", "title": "The use of freeze-fracture and negative staining techniques to study the ultrastructure of melanosomes isolated from B16 melanoma.", "content": "Freeze-fracture negative staining methods were used to investigate the structure of melanosomes isolated from B16 melanoma. The findings demonstrated the presence of a melanosomal double-layered membrane. Negative staining procedure showed that the melanosomal membrane is sometimes ruptured, displaced or peeled off during the purification process. Fractured melanosomes showed melanin spheres with a mean diameter of 24 nm. This compares with a mean diameter of 26 nm for the melanin spheres revealed by negative staining. The granular appearance of fractured mature melanosomes is due to the fracture following a random path between melanin spheres.", "contents": "The use of freeze-fracture and negative staining techniques to study the ultrastructure of melanosomes isolated from B16 melanoma. Freeze-fracture negative staining methods were used to investigate the structure of melanosomes isolated from B16 melanoma. The findings demonstrated the presence of a melanosomal double-layered membrane. Negative staining procedure showed that the melanosomal membrane is sometimes ruptured, displaced or peeled off during the purification process. Fractured melanosomes showed melanin spheres with a mean diameter of 24 nm. This compares with a mean diameter of 26 nm for the melanin spheres revealed by negative staining. The granular appearance of fractured mature melanosomes is due to the fracture following a random path between melanin spheres."} {"id": "PMID:1254525", "title": "Experimental production of ridges on rabbit articular cartilage: a scanning electron microscope study.", "content": "The surface of normal rabbit articular cartilage attached to subchondral bone has a pitted appearance when examined with the scanning electron microsope. It is thought that these pits are similar to those seen in human cartilage and that they reflect the presence of underlying chondrocytes and lacunae, shrunken by preparative procedures. Ridges or undulations were not seen on the normal articular surface with the scanning electron microscope but complex systems of coarse and fine ridges were produced when cartilage was damaged by cutting, by making a hole in it or by detaching it from subchondral bone. Humps or mound-like elevations also developed in some instances when cartilage was damaged by cutting or by making a hole in its substance.", "contents": "Experimental production of ridges on rabbit articular cartilage: a scanning electron microscope study. The surface of normal rabbit articular cartilage attached to subchondral bone has a pitted appearance when examined with the scanning electron microsope. It is thought that these pits are similar to those seen in human cartilage and that they reflect the presence of underlying chondrocytes and lacunae, shrunken by preparative procedures. Ridges or undulations were not seen on the normal articular surface with the scanning electron microscope but complex systems of coarse and fine ridges were produced when cartilage was damaged by cutting, by making a hole in it or by detaching it from subchondral bone. Humps or mound-like elevations also developed in some instances when cartilage was damaged by cutting or by making a hole in its substance."} {"id": "PMID:1254526", "title": "The structural basis of the philtrum and the contour of the vermilion border: a study of the musculature of the upper lip.", "content": "The course and insertion pattern of muscle fibres in the philtrum of the human upper lip were studied in seven post-mortem specimens using serial histological sections and a reconstruction method using sheets of Plexiglas. The fibres of the musculus orbicularis oris entering the upper lip from one side were observed to decussate in the midline and proceed to insert into the skin of the opposite side lateral to the philtral groove. The philtral ridges appeared to represent the medial borders of bilateral muscle insertion zones of the lip in which the fibres of the m. orbicularis oris raised the level of the skin by splaying out and inserting into it. Contributions to philtral form also came from the musculus levator labii superioris as it descended as far medially as the philtral ridge to insert into the vermilion border lateral to the median groove, and from fibres of the musculus nasalis which inserted into the philtral ridges superiorly. The philtral groove corresponded to the more compact median decussation of the orbicularis oris where lip thickness was also reduced by the relative absence of muscle fibre insertions into the skin. The displacment of the vermilion border giving rise to Cupid's bow appeared to result from the lifting action of the m. levator labii superioris lateral to the median groove in conjuction with a depressor action by the m. orbicularis oris on the median tubercle.", "contents": "The structural basis of the philtrum and the contour of the vermilion border: a study of the musculature of the upper lip. The course and insertion pattern of muscle fibres in the philtrum of the human upper lip were studied in seven post-mortem specimens using serial histological sections and a reconstruction method using sheets of Plexiglas. The fibres of the musculus orbicularis oris entering the upper lip from one side were observed to decussate in the midline and proceed to insert into the skin of the opposite side lateral to the philtral groove. The philtral ridges appeared to represent the medial borders of bilateral muscle insertion zones of the lip in which the fibres of the m. orbicularis oris raised the level of the skin by splaying out and inserting into it. Contributions to philtral form also came from the musculus levator labii superioris as it descended as far medially as the philtral ridge to insert into the vermilion border lateral to the median groove, and from fibres of the musculus nasalis which inserted into the philtral ridges superiorly. The philtral groove corresponded to the more compact median decussation of the orbicularis oris where lip thickness was also reduced by the relative absence of muscle fibre insertions into the skin. The displacment of the vermilion border giving rise to Cupid's bow appeared to result from the lifting action of the m. levator labii superioris lateral to the median groove in conjuction with a depressor action by the m. orbicularis oris on the median tubercle."} {"id": "PMID:1254527", "title": "An ultrastructural study of implantation in the golden hamster. I. Loss of the zona pellucida and initial attachment to the uterine epithelium.", "content": "Forty five blastocysts from 14 golden hamsters were examined in situ with light and electron microscopy between 3 and 4 days of pregnancy (post-ovulation). At 3 days blastocysts remained free within the uterine lumen with their zonae pellucidae intact. At various intervals between 3 days and 3 days 6 hours a gradual thinning of the zona occurred, indicating the possible presence of a lytic factor which aids in the removal of the zona pellucida. Blastocysts at 3 days 8 hours had lost their zonae pellucidae, and by 3 1/2 days they were completely enclosed by the uterine pithelium. By 4 days a more intimate association between the juxtaposed trophoblast and uterine epithelium occurred, leaving intermittent deposits of electron-dense material between the adjoining plasma membranes.", "contents": "An ultrastructural study of implantation in the golden hamster. I. Loss of the zona pellucida and initial attachment to the uterine epithelium. Forty five blastocysts from 14 golden hamsters were examined in situ with light and electron microscopy between 3 and 4 days of pregnancy (post-ovulation). At 3 days blastocysts remained free within the uterine lumen with their zonae pellucidae intact. At various intervals between 3 days and 3 days 6 hours a gradual thinning of the zona occurred, indicating the possible presence of a lytic factor which aids in the removal of the zona pellucida. Blastocysts at 3 days 8 hours had lost their zonae pellucidae, and by 3 1/2 days they were completely enclosed by the uterine pithelium. By 4 days a more intimate association between the juxtaposed trophoblast and uterine epithelium occurred, leaving intermittent deposits of electron-dense material between the adjoining plasma membranes."} {"id": "PMID:1254528", "title": "A histochemical study of human fetal skin.", "content": "Glycogen and alkaline phosphatase have been studied in human fetal epidermis between the 28th and 182nd days of gestation. Early on, bladder cells rich in glycogen and alkaline phosphatase are present in the periderm. After 140 days, however, keratin appears in the superficial layers of the periderm; the bladder cells degenerate and become 'rosette' cells, and glycogen and alkaline phosphatase begin to disappear. It is suggested from this evidence that, in early fetal life, before the onset of keratinization, glucose is absorbed from the amniotic fluid and stored as glycogen in the periderm.", "contents": "A histochemical study of human fetal skin. Glycogen and alkaline phosphatase have been studied in human fetal epidermis between the 28th and 182nd days of gestation. Early on, bladder cells rich in glycogen and alkaline phosphatase are present in the periderm. After 140 days, however, keratin appears in the superficial layers of the periderm; the bladder cells degenerate and become 'rosette' cells, and glycogen and alkaline phosphatase begin to disappear. It is suggested from this evidence that, in early fetal life, before the onset of keratinization, glucose is absorbed from the amniotic fluid and stored as glycogen in the periderm."} {"id": "PMID:1254529", "title": "Further observations on the pharyngeal hypophysis and the postsphenoid in the mature male rat.", "content": "In an investigation into the pharyngeal hypophysis and the postsphenoid using seven hypophysectiomized mature male rats, a pharyngeal hypophysis and a craniopharyngeal canal was found in each of two rats. Cellular differentiation was noted in the pharyngeal hypophysis in both rats. In one rat the pharyngeal hypophysis was markedly larger than any seen to date. In both rats the pharyngeal hypophysis was continuous with tissue of similar histological appearance which extended the full length of the cranio-pharyngeal canal. The histological appearance of the pharyngeal hypophysis and of the specific intra-canal tissue was also similar to that of cystic areas in the sellar adenohypophysis in the normal rat. The data arising from the present investigation indicate that a well-defined cranio-pharyngeal canal can occur in the rat. The data also support the assumption that the sellar adenohypophysis may be continuous with specific tissue within a cranio-pharyngeal canal. The significance of the data in terms of reactive hypertrophy and cellular differentiation of the pharyngeal hypophysis and the specific intra-canal tissue following hypophysectomy must await further data on the volume and histology of such tissue in normal rats which possess a cranio-pharyngeal canal.", "contents": "Further observations on the pharyngeal hypophysis and the postsphenoid in the mature male rat. In an investigation into the pharyngeal hypophysis and the postsphenoid using seven hypophysectiomized mature male rats, a pharyngeal hypophysis and a craniopharyngeal canal was found in each of two rats. Cellular differentiation was noted in the pharyngeal hypophysis in both rats. In one rat the pharyngeal hypophysis was markedly larger than any seen to date. In both rats the pharyngeal hypophysis was continuous with tissue of similar histological appearance which extended the full length of the cranio-pharyngeal canal. The histological appearance of the pharyngeal hypophysis and of the specific intra-canal tissue was also similar to that of cystic areas in the sellar adenohypophysis in the normal rat. The data arising from the present investigation indicate that a well-defined cranio-pharyngeal canal can occur in the rat. The data also support the assumption that the sellar adenohypophysis may be continuous with specific tissue within a cranio-pharyngeal canal. The significance of the data in terms of reactive hypertrophy and cellular differentiation of the pharyngeal hypophysis and the specific intra-canal tissue following hypophysectomy must await further data on the volume and histology of such tissue in normal rats which possess a cranio-pharyngeal canal."} {"id": "PMID:1254530", "title": "Some aspects of amoeboid microglia in the corpus callosum and neighbouring regions of neonatal rats.", "content": "The distribution and form of amoeboid microglia in the brain of neonatal rats have been studied with the light and electron microscope. With the silver carbonate method of Rio-Hortega, two major 'colonies' of amoeboid microglia are identified: (1) in the supraventricular corpus callosum in which the nerve fibres are widely spaced, and (2) at the medial angle of the lateral ventricle inferior to the corpus callosum. Scattered amoeboid cells are also seen in the cavum septum pellucidum and in the lumen of the lateral ventricle. Associated with the subependyma forming the roof of the lateral ventricle there are also numerous amoeboid cells. Ultrastructural studies show that the subependyma includes cellular elements with features intermediate between those of immature subependymal cells and full-blown amoeboid microglia. It is suggested that the latter are derived from the subependymal cells and that, once they are formed, they leave the subependyma and migrate into the corpus callosum and elsewhere. With the metallic stain, the amoeboid microglia present a wide diversity of appearances, some of which bear a close resemblance to typical microglia. It is therefore suggested that amoeboid microglia change into typical microglia. The present study clearly demonstrates that amoeboid microglia are active phagocytes. Their cytoplasm is heavily loaded with secretory granules (lysosomes) and give a positive reaction with PAS and acid phosphatase.", "contents": "Some aspects of amoeboid microglia in the corpus callosum and neighbouring regions of neonatal rats. The distribution and form of amoeboid microglia in the brain of neonatal rats have been studied with the light and electron microscope. With the silver carbonate method of Rio-Hortega, two major 'colonies' of amoeboid microglia are identified: (1) in the supraventricular corpus callosum in which the nerve fibres are widely spaced, and (2) at the medial angle of the lateral ventricle inferior to the corpus callosum. Scattered amoeboid cells are also seen in the cavum septum pellucidum and in the lumen of the lateral ventricle. Associated with the subependyma forming the roof of the lateral ventricle there are also numerous amoeboid cells. Ultrastructural studies show that the subependyma includes cellular elements with features intermediate between those of immature subependymal cells and full-blown amoeboid microglia. It is suggested that the latter are derived from the subependymal cells and that, once they are formed, they leave the subependyma and migrate into the corpus callosum and elsewhere. With the metallic stain, the amoeboid microglia present a wide diversity of appearances, some of which bear a close resemblance to typical microglia. It is therefore suggested that amoeboid microglia change into typical microglia. The present study clearly demonstrates that amoeboid microglia are active phagocytes. Their cytoplasm is heavily loaded with secretory granules (lysosomes) and give a positive reaction with PAS and acid phosphatase."} {"id": "PMID:1254531", "title": "Observations on the source of embryonic myocardioblasts.", "content": "The light and electron microscopic appearance of mesenchymal and myoblastic tissue in the embryonic heart is described. The similarity in the morphological appearance of all mesenchymal cells is pointed out, whether they occur in atrioventricular cushion tissue, the ridge tissue of the bulbus, cordis, sub-epicardial tissue or in mesenchyme elsewhere in the embryo. Cells intermediate in their ultrastructure between mesenchymal cells and myoblasts are found. The significance of such cells is discussed and the suggestion made that their appearance is consistent with their representing stages in the differentiation of mesenchymal cells into myoblasts.", "contents": "Observations on the source of embryonic myocardioblasts. The light and electron microscopic appearance of mesenchymal and myoblastic tissue in the embryonic heart is described. The similarity in the morphological appearance of all mesenchymal cells is pointed out, whether they occur in atrioventricular cushion tissue, the ridge tissue of the bulbus, cordis, sub-epicardial tissue or in mesenchyme elsewhere in the embryo. Cells intermediate in their ultrastructure between mesenchymal cells and myoblasts are found. The significance of such cells is discussed and the suggestion made that their appearance is consistent with their representing stages in the differentiation of mesenchymal cells into myoblasts."} {"id": "PMID:1254532", "title": "A presomite human embryo of Horizon VII.", "content": "A presomite embryo of Horizon VII aged approximately 18 days is described and illustrated. It is compared with some other embryos of a similar age, and a considerable variation of histological characteristics within the same Horizon is noted.", "contents": "A presomite human embryo of Horizon VII. A presomite embryo of Horizon VII aged approximately 18 days is described and illustrated. It is compared with some other embryos of a similar age, and a considerable variation of histological characteristics within the same Horizon is noted."} {"id": "PMID:1254533", "title": "Quantitative changes in neuroglia in the white matter of the mouse brain following hypoxic stress.", "content": "Two experimental and one control group of 70-80 day old mice were used in this study. The two experimental groups were subjected to hypoxia for 2 days in a decompression chamber at 390 mmHg. The animals in one experimental group were killed on removal from the chamber (hypoxic group) while those in the other (recovery group) were allowed to recover at sea-level atmospheric pressure for one week before being killed. Semithin, toluidine blue stained sections from the anterior limb of the anterior commissure were examined to find whether any quantitative changes occurred in the neuroglia with hypoxic stress. The following changes were observed: (1) The percentage of astrocytes in the hypoxic and recovery groups was significantly (P less than 0-005) lower than in the control group. (2) The percentage of oligodendrocytes in the hypoxic and recovery groups was significantly (P less than 0-001) higher than in the control group. (3) The percentage of microglia in the recovery groups was significantly (P less than 0-02) lower than in either of the other two groups. (4) The percentage of astrocytes in the recovery group was slightly (2-1%) higher than in the hypoxic group, and although not statistically significant, this result suggested that a slow return to normal might be occurring. (5) Little change was observed in cell density. The possible significance of these changes is discussed. I should like to express my indebtedness to Dr E.J. Clegg of the Department of Anatomy, Sheffield University, for the use of the decompression chamber, for his advice and help in the preparation of the control and experimental animals, and also for his hospitality throughout the duration of the experiments. Thanks are also due to Mrs Sheila Ramsay for her careful preparation of the perfusing fluids, and to Mrs Dawn Alexander for typing the manuscript.", "contents": "Quantitative changes in neuroglia in the white matter of the mouse brain following hypoxic stress. Two experimental and one control group of 70-80 day old mice were used in this study. The two experimental groups were subjected to hypoxia for 2 days in a decompression chamber at 390 mmHg. The animals in one experimental group were killed on removal from the chamber (hypoxic group) while those in the other (recovery group) were allowed to recover at sea-level atmospheric pressure for one week before being killed. Semithin, toluidine blue stained sections from the anterior limb of the anterior commissure were examined to find whether any quantitative changes occurred in the neuroglia with hypoxic stress. The following changes were observed: (1) The percentage of astrocytes in the hypoxic and recovery groups was significantly (P less than 0-005) lower than in the control group. (2) The percentage of oligodendrocytes in the hypoxic and recovery groups was significantly (P less than 0-001) higher than in the control group. (3) The percentage of microglia in the recovery groups was significantly (P less than 0-02) lower than in either of the other two groups. (4) The percentage of astrocytes in the recovery group was slightly (2-1%) higher than in the hypoxic group, and although not statistically significant, this result suggested that a slow return to normal might be occurring. (5) Little change was observed in cell density. The possible significance of these changes is discussed. I should like to express my indebtedness to Dr E.J. Clegg of the Department of Anatomy, Sheffield University, for the use of the decompression chamber, for his advice and help in the preparation of the control and experimental animals, and also for his hospitality throughout the duration of the experiments. Thanks are also due to Mrs Sheila Ramsay for her careful preparation of the perfusing fluids, and to Mrs Dawn Alexander for typing the manuscript."} {"id": "PMID:1254534", "title": "A pilot study of cell production by the ganglionic eminences of the developing mouse brain.", "content": "Cell production in the medial and lateral ganglionic eminences in pre- and post-natal mouse brains was studied by recording the number, location and plane of cleavage of mitotic figures. The site of maximum cell production shifted progressively from the ependymal layer to an adjacent sub-ependymal proliferative compartment. In the latter, mitosis occurred without the nuclei participating in the migratory movement to the ventricular surface which is characteristic of the nuclei of the ependymal compartment. The sub-ependymal compartment persisted vestigially into post-natal life as the well known sub-ependymal layer.", "contents": "A pilot study of cell production by the ganglionic eminences of the developing mouse brain. Cell production in the medial and lateral ganglionic eminences in pre- and post-natal mouse brains was studied by recording the number, location and plane of cleavage of mitotic figures. The site of maximum cell production shifted progressively from the ependymal layer to an adjacent sub-ependymal proliferative compartment. In the latter, mitosis occurred without the nuclei participating in the migratory movement to the ventricular surface which is characteristic of the nuclei of the ependymal compartment. The sub-ependymal compartment persisted vestigially into post-natal life as the well known sub-ependymal layer."} {"id": "PMID:1254540", "title": "An experimental analysis of \"spillover\" effects on the social interaction of behaviorally handicapped preschool children.", "content": "The effects of prompting and social reinforcement directed to target subjects on their social behavior and that of peers who never received prompting and reinforcement for positive social behavior, were examined. In a combined reversal and multiple-baseline design, three behaviorally handicapped preschool boys who exhibited divergent social behavior repertoires and varied histories with social reinforcement events were sequentially exposed to intervention conditions in order to investigate \"spillover\" of treatment effects. Prompting and reinforcement increased positive social behavior and decreased negative social behavior emitted by all target subjects. The results also demonstrated a \"spillover\" effect on two target subjects, who at various times were not under intervention, and on the peers as well. The findings suggest that: (a) the direct and indirect effects of intervention procedures may be enhanced by designing treatment based on the social repertoire and reinforcement histories of the subjects; and (b) the treatment \"spillover\" effect may be increased by applying procedures to two children at once, rather than at one at a time.", "contents": "An experimental analysis of \"spillover\" effects on the social interaction of behaviorally handicapped preschool children. The effects of prompting and social reinforcement directed to target subjects on their social behavior and that of peers who never received prompting and reinforcement for positive social behavior, were examined. In a combined reversal and multiple-baseline design, three behaviorally handicapped preschool boys who exhibited divergent social behavior repertoires and varied histories with social reinforcement events were sequentially exposed to intervention conditions in order to investigate \"spillover\" of treatment effects. Prompting and reinforcement increased positive social behavior and decreased negative social behavior emitted by all target subjects. The results also demonstrated a \"spillover\" effect on two target subjects, who at various times were not under intervention, and on the peers as well. The findings suggest that: (a) the direct and indirect effects of intervention procedures may be enhanced by designing treatment based on the social repertoire and reinforcement histories of the subjects; and (b) the treatment \"spillover\" effect may be increased by applying procedures to two children at once, rather than at one at a time."} {"id": "PMID:1254541", "title": "Self-recording in training girls to increase work and evoke staff praise in an institution for offenders.", "content": "Self-recording procedures were used by four adolescent girls to increase work and comments (cues) that evoked staff praise during vocational training sessions in a maximum-security institution for offenders. The girls were selected on the basis of their not responding to a staff-directed token program. The self-recording procedures were directed by a therapist who saw the girls outside the vocational training sessions. According to a multiple-baseline design, self-recording of work was introduced sequentially to each of the two or three settings the girls attended each day. A few days after work had increased, self-recording of cues was introduced. Tokens were delivered by the therapist for work and cues recorded by the girls. Work and cues increased following self-recording for three of the girls and increased cues evoked higher rates of staff praise. Girl and staff behaviors were maintained during short follow-up periods when tokens were not given for the girls' records. The procedures failed to effect desirable changes with a fourth girl's work and self-recording of work was terminated without introducing cueing.", "contents": "Self-recording in training girls to increase work and evoke staff praise in an institution for offenders. Self-recording procedures were used by four adolescent girls to increase work and comments (cues) that evoked staff praise during vocational training sessions in a maximum-security institution for offenders. The girls were selected on the basis of their not responding to a staff-directed token program. The self-recording procedures were directed by a therapist who saw the girls outside the vocational training sessions. According to a multiple-baseline design, self-recording of work was introduced sequentially to each of the two or three settings the girls attended each day. A few days after work had increased, self-recording of cues was introduced. Tokens were delivered by the therapist for work and cues recorded by the girls. Work and cues increased following self-recording for three of the girls and increased cues evoked higher rates of staff praise. Girl and staff behaviors were maintained during short follow-up periods when tokens were not given for the girls' records. The procedures failed to effect desirable changes with a fourth girl's work and self-recording of work was terminated without introducing cueing."} {"id": "PMID:1254542", "title": "Contingent observation: an effective and acceptable procedure for reducing disruptive behavior of young children in a group setting.", "content": "Since a major task of childhood is learning to get along in a group without disrupting other children's activities, caregivers need explicit guidelines for gentle but effective procedures for dealing with disruptive behaviors in child-care settings. In a day-care center for normal 1- and 2-yr.-old children, an effort was made to develop a procedure that appeared sufficiently humane and educational to be acceptable to parents and day-care workers, and yet effective in reducing disruptive play behaviors. Caregivers used the occasion of disruptive behavior to instruct the child in appropriate alternatives, then had the child sit on the periphery and observe the appropriate social behavior of the other children \"sit and watch\", for a brief period before inviting him or her to rejoin the play activities. The effectiveness of this procedure was compared with a method commonly recommended for the use with young children: instructing the child, then distracting or redirecting the child to an alternative toy or activity. Contingent observation, combining instruction with a brief timeout (from being a participant in an activity to becoming an observer of the activity), proved considerably more effective in maintaining low levels of disruptions and was considered by caregivers and parents to be an appropriate and socially acceptable method of dealing with young children's disruptive behaviors. Therefore, contingent observation can be recommended for general use in day-care programs for young children.", "contents": "Contingent observation: an effective and acceptable procedure for reducing disruptive behavior of young children in a group setting. Since a major task of childhood is learning to get along in a group without disrupting other children's activities, caregivers need explicit guidelines for gentle but effective procedures for dealing with disruptive behaviors in child-care settings. In a day-care center for normal 1- and 2-yr.-old children, an effort was made to develop a procedure that appeared sufficiently humane and educational to be acceptable to parents and day-care workers, and yet effective in reducing disruptive play behaviors. Caregivers used the occasion of disruptive behavior to instruct the child in appropriate alternatives, then had the child sit on the periphery and observe the appropriate social behavior of the other children \"sit and watch\", for a brief period before inviting him or her to rejoin the play activities. The effectiveness of this procedure was compared with a method commonly recommended for the use with young children: instructing the child, then distracting or redirecting the child to an alternative toy or activity. Contingent observation, combining instruction with a brief timeout (from being a participant in an activity to becoming an observer of the activity), proved considerably more effective in maintaining low levels of disruptions and was considered by caregivers and parents to be an appropriate and socially acceptable method of dealing with young children's disruptive behaviors. Therefore, contingent observation can be recommended for general use in day-care programs for young children."} {"id": "PMID:1254543", "title": "Interactions between teacher guidance and contingent access to play in developing preacademic skills of deviant preschool children.", "content": "Token-mediated access to play and snacks was made contingent on completion of academic tasks in the Baseline Experiment. This contingency produced stable completion rates that were subsequently doubled, and then tripled, for four deviant children in a special preschool. A reversal design demonstrated that the contingency was functional in maintaining the children's rates of task completion. The Guidance Experiment examined the role of a social event, teacher guidance, in the acquisition of task-completion skills, in a multiple-baseline-across-tasks design (with reversals). The analysis demonstrated that teacher guidance was an important supplement to the token-mediated contingency in establishing significant increases in task completions for a second group of three deviant children in the special class. The importance of teacher guidance was related to the difficulty level of the children's tasks.", "contents": "Interactions between teacher guidance and contingent access to play in developing preacademic skills of deviant preschool children. Token-mediated access to play and snacks was made contingent on completion of academic tasks in the Baseline Experiment. This contingency produced stable completion rates that were subsequently doubled, and then tripled, for four deviant children in a special preschool. A reversal design demonstrated that the contingency was functional in maintaining the children's rates of task completion. The Guidance Experiment examined the role of a social event, teacher guidance, in the acquisition of task-completion skills, in a multiple-baseline-across-tasks design (with reversals). The analysis demonstrated that teacher guidance was an important supplement to the token-mediated contingency in establishing significant increases in task completions for a second group of three deviant children in the special class. The importance of teacher guidance was related to the difficulty level of the children's tasks."} {"id": "PMID:1254544", "title": "Quantitation of o- and p-sulfamoylbenzoic acids in commerical saccharin by high-performance liquid chromatography.", "content": "Quantitation of o- and p-sulfamoylbenzoic acid residues in saccharin and its sodium salt is achieved by a method comprising methanolic extraction and high-performance ion exchange chromatography. A commercially available anion exchange column was employed with an aqueous buffered (pH 9.2) mobile phase. As little as 80 ppm of the ortho-isomer and 25 ppm of the para-isomer can be accurately determined. The levels of detectability (2 times noise) are estimated as 8 ppm (0.16 mug on column) and 2.5 ppm (0.05 mug on column), respectively. Recoveries from saccharin ranged from 92.7 to 96.5% (ortho) and from 92.2 to 103.3% (para). Recoveries from the sodium salt ranged from 93.1 to 104.4% (ortho) and from 93.5 to 97.8% (para). Of 9 other potential saccharin impurities tested separately, only one was found to interfere slightly in the chromatographic part of the procedure.", "contents": "Quantitation of o- and p-sulfamoylbenzoic acids in commerical saccharin by high-performance liquid chromatography. Quantitation of o- and p-sulfamoylbenzoic acid residues in saccharin and its sodium salt is achieved by a method comprising methanolic extraction and high-performance ion exchange chromatography. A commercially available anion exchange column was employed with an aqueous buffered (pH 9.2) mobile phase. As little as 80 ppm of the ortho-isomer and 25 ppm of the para-isomer can be accurately determined. The levels of detectability (2 times noise) are estimated as 8 ppm (0.16 mug on column) and 2.5 ppm (0.05 mug on column), respectively. Recoveries from saccharin ranged from 92.7 to 96.5% (ortho) and from 92.2 to 103.3% (para). Recoveries from the sodium salt ranged from 93.1 to 104.4% (ortho) and from 93.5 to 97.8% (para). Of 9 other potential saccharin impurities tested separately, only one was found to interfere slightly in the chromatographic part of the procedure."} {"id": "PMID:1254545", "title": "Gas-liquid chromatographic determination of famphur and its oxygen analog in tissues of reindeer and cattle.", "content": "A gas chromatography equipped with a flame photometric detector operating in the phosphorus mode provided a sensitive method for determining residues of famphur, O,O-dimethyl O-[p-(dimethylsulfamoyl)phenyl]phosphorothioate, and its oxygen analog in reindeer and cattle tissues. With extraction and cleanup, 0.025 ppm famphur and 0.06 ppm oxygen analog could be detected in the body tissues. Recoveries of 73-100% were obtained from fat, muscle, liver, and kidney.", "contents": "Gas-liquid chromatographic determination of famphur and its oxygen analog in tissues of reindeer and cattle. A gas chromatography equipped with a flame photometric detector operating in the phosphorus mode provided a sensitive method for determining residues of famphur, O,O-dimethyl O-[p-(dimethylsulfamoyl)phenyl]phosphorothioate, and its oxygen analog in reindeer and cattle tissues. With extraction and cleanup, 0.025 ppm famphur and 0.06 ppm oxygen analog could be detected in the body tissues. Recoveries of 73-100% were obtained from fat, muscle, liver, and kidney."} {"id": "PMID:1254546", "title": "Gas-liquid chromatographic determination of 3,6-dichloropicolinic acid in soils.", "content": "A gas-liquid chromatographic (GLC) method has been developed for the determination of the experimental herbicide 3,6-dichloropicolinic acid (Dowco 290) in soils. The method involves extraction of 1 g soil samples with 1N NaCl at approximately pH 7, methylation with diazomethane utilizing a microgenerator, and detection by electron capture GLC. Interferences are small, so that a cleanup step is not necessary even at the 6 ppb level. The procedure is rapid, requiring only 45 min/sample. Recoveries range from 84 to 94% at the 6-1000 ppb level with a minimum detectable limit of 6 ppb. Standard deviations for the percentage recovery values vary from 10.9 to 2.3 for the tested range of 6.7-670 ppb, respectively.", "contents": "Gas-liquid chromatographic determination of 3,6-dichloropicolinic acid in soils. A gas-liquid chromatographic (GLC) method has been developed for the determination of the experimental herbicide 3,6-dichloropicolinic acid (Dowco 290) in soils. The method involves extraction of 1 g soil samples with 1N NaCl at approximately pH 7, methylation with diazomethane utilizing a microgenerator, and detection by electron capture GLC. Interferences are small, so that a cleanup step is not necessary even at the 6 ppb level. The procedure is rapid, requiring only 45 min/sample. Recoveries range from 84 to 94% at the 6-1000 ppb level with a minimum detectable limit of 6 ppb. Standard deviations for the percentage recovery values vary from 10.9 to 2.3 for the tested range of 6.7-670 ppb, respectively."} {"id": "PMID:1254547", "title": "Comparison of analytical methods for metribuzin.", "content": "Determinations of the active ingredient in technical and formulated metribuzin were compared by gas-liquid chromatography (GLC) using various solvents, infrared (IR) spectrophotometry, and high-pressure liquid chromatography (HPLC). Ketones could not be used as a solvent for GLC analysis because of Schiff base formation. The GLC method using ethylene glycol monomethyl ether gave results about 1% higher for technical metribuzin than the other methods. GLC using methylene chloride solvent agreed with IR and HPLC results to within 0.4%. GLC using methylene chloride is the preferred method.", "contents": "Comparison of analytical methods for metribuzin. Determinations of the active ingredient in technical and formulated metribuzin were compared by gas-liquid chromatography (GLC) using various solvents, infrared (IR) spectrophotometry, and high-pressure liquid chromatography (HPLC). Ketones could not be used as a solvent for GLC analysis because of Schiff base formation. The GLC method using ethylene glycol monomethyl ether gave results about 1% higher for technical metribuzin than the other methods. GLC using methylene chloride solvent agreed with IR and HPLC results to within 0.4%. GLC using methylene chloride is the preferred method."} {"id": "PMID:1254548", "title": "Collaborative study of the colorimetric determination of nitrate and nitrite in cheese.", "content": "A quantitative colorimetric method for the determination of nitrate and nitrite in cheese has been subjected to collaborative study. The method includes clarification of an aqueous extract of cheese with zinc hydroxide, reduction of nitrate to nitrite via a spongy cadmium collumn (the nitrite originally present is unaltered), diazotization of sulfanilic acid with the nitrite, and coupling with 1-naphthylamine hydrochloride to form a pink azo dye whose absorbance is measured at 522 nm. The spectrophotometric responses are compared to a standard curve. In samples containing both nitrate and nitrite, nitrate is determined by difference. A standard deviation of 5.5 was obtained (5 of 6 collaborators) when a cheese sample spiked with 276 ppm sodium nitrate was analyzed by the method. The method has been adopted as official first action.", "contents": "Collaborative study of the colorimetric determination of nitrate and nitrite in cheese. A quantitative colorimetric method for the determination of nitrate and nitrite in cheese has been subjected to collaborative study. The method includes clarification of an aqueous extract of cheese with zinc hydroxide, reduction of nitrate to nitrite via a spongy cadmium collumn (the nitrite originally present is unaltered), diazotization of sulfanilic acid with the nitrite, and coupling with 1-naphthylamine hydrochloride to form a pink azo dye whose absorbance is measured at 522 nm. The spectrophotometric responses are compared to a standard curve. In samples containing both nitrate and nitrite, nitrate is determined by difference. A standard deviation of 5.5 was obtained (5 of 6 collaborators) when a cheese sample spiked with 276 ppm sodium nitrate was analyzed by the method. The method has been adopted as official first action."} {"id": "PMID:1254549", "title": "Collaborative study of a semiautomated fluorometric method for the determination of reserpine in tablets.", "content": "A semiautomated fluorometric method for the determination of resperpine in tablets was collaboratively studied by 7 laboratories. The method is a modification of the semiautomated method of Urb\u00e1nyi and Stober, which involves formation of a fluorogen with vanadium pentoxide. Collaborators were supplied with 3 composites, each from a different dosage level of commercial tablets. The results obtained agreed well with the AOAC manual fluorometric method; coefficients of variation ranged from 0.45 to 2.70%. The method has been adopted as official first action.", "contents": "Collaborative study of a semiautomated fluorometric method for the determination of reserpine in tablets. A semiautomated fluorometric method for the determination of resperpine in tablets was collaboratively studied by 7 laboratories. The method is a modification of the semiautomated method of Urb\u00e1nyi and Stober, which involves formation of a fluorogen with vanadium pentoxide. Collaborators were supplied with 3 composites, each from a different dosage level of commercial tablets. The results obtained agreed well with the AOAC manual fluorometric method; coefficients of variation ranged from 0.45 to 2.70%. The method has been adopted as official first action."} {"id": "PMID:1254550", "title": "Transport of vitamin B12 in Escherichia coli: common receptor system for vitamin B12 and bacteriophage BF23 on the outer membrane of the cell envelope.", "content": "We showed previously that the outer membrane of the Escherichia coli cell envelope normally contains about 200 to 250 B12 receptors, and that these receptors function both in B12 transport and as receptors for the E colicins. This paper shows that this receptor system is also shared with bacteriophage BF23. A strong positive correlation was observed between the number of B12 receptors per cell and the rate of adsorption of BF23. Cells from mutant strains that lacked B12 receptors did not adsorb BF23 particles. The rate of adsorption of BF23 to cells of a merodiploid strain (RK4151), with about 550 B12 receptors per cell, was approximately double that to cells of a normal, haploid strain. The adsorption of BF23 to hole cells, cell envelopes, outer membrane particles, and solubilized outer membranes was inhibited by vitamin B12, with 50% inhibition at B12 concentrations in the range of 0.5 to 2.0 nM. These values are close to the observed KS for B12 binding to the B12 receptors. Vitamin B12 concentrations as high as 100 nM did not inhibit adsorption of bacteriophages T5, T6, and lambdacI to cells of sensitive strains of E. coli. Bacteriophage BF23 inhibited B12 transport by whole cells and was shown to be a competitive inhibitor of B12 binding to isolated cell envelope particles. The B12/BF23 receptors from E. coli strains KBT069 (btuB69) and RK4104 (btuB69) were fully active, but the number per cell was reduced to an average value of about 0.5.", "contents": "Transport of vitamin B12 in Escherichia coli: common receptor system for vitamin B12 and bacteriophage BF23 on the outer membrane of the cell envelope. We showed previously that the outer membrane of the Escherichia coli cell envelope normally contains about 200 to 250 B12 receptors, and that these receptors function both in B12 transport and as receptors for the E colicins. This paper shows that this receptor system is also shared with bacteriophage BF23. A strong positive correlation was observed between the number of B12 receptors per cell and the rate of adsorption of BF23. Cells from mutant strains that lacked B12 receptors did not adsorb BF23 particles. The rate of adsorption of BF23 to cells of a merodiploid strain (RK4151), with about 550 B12 receptors per cell, was approximately double that to cells of a normal, haploid strain. The adsorption of BF23 to hole cells, cell envelopes, outer membrane particles, and solubilized outer membranes was inhibited by vitamin B12, with 50% inhibition at B12 concentrations in the range of 0.5 to 2.0 nM. These values are close to the observed KS for B12 binding to the B12 receptors. Vitamin B12 concentrations as high as 100 nM did not inhibit adsorption of bacteriophages T5, T6, and lambdacI to cells of sensitive strains of E. coli. Bacteriophage BF23 inhibited B12 transport by whole cells and was shown to be a competitive inhibitor of B12 binding to isolated cell envelope particles. The B12/BF23 receptors from E. coli strains KBT069 (btuB69) and RK4104 (btuB69) were fully active, but the number per cell was reduced to an average value of about 0.5."} {"id": "PMID:1254551", "title": "Ultrastructure of rigid and lignified forage tissue degradation by a filamentous rumen microorganism.", "content": "A small (less than 1 mum)-filamentous, branching microorganism was observed in Gram-stained smears of the rumen microflora and was found to degrade tissues in forage samples incubated in vitro and in vivo with rumen fluid and observed by scanning and transmission electron microscopy. The microbe had prokaryotic cytoplasmic features and a gram-positive type of cell wall structure. Round to oval bodies apparently attached to hyphae resembled the sporulation pattern reported for Micromonospora. Filaments and rod and coccal forms of the microbe degraded rigid forage cell walls and lignified, thick-walled sclerenchymal cells. Location of the microbe at a slight distance from the degraded zones suggested the action of extracellular enzymes. The presence of a microbe with the capability of degrading lignified tissue represents an important and unique function in the rumen ecosystem.", "contents": "Ultrastructure of rigid and lignified forage tissue degradation by a filamentous rumen microorganism. A small (less than 1 mum)-filamentous, branching microorganism was observed in Gram-stained smears of the rumen microflora and was found to degrade tissues in forage samples incubated in vitro and in vivo with rumen fluid and observed by scanning and transmission electron microscopy. The microbe had prokaryotic cytoplasmic features and a gram-positive type of cell wall structure. Round to oval bodies apparently attached to hyphae resembled the sporulation pattern reported for Micromonospora. Filaments and rod and coccal forms of the microbe degraded rigid forage cell walls and lignified, thick-walled sclerenchymal cells. Location of the microbe at a slight distance from the degraded zones suggested the action of extracellular enzymes. The presence of a microbe with the capability of degrading lignified tissue represents an important and unique function in the rumen ecosystem."} {"id": "PMID:1254552", "title": "Change in quantity of lipids and cell size during intracytoplasmic membrane formation in Gluconobacter oxydans.", "content": "Electron microscopy previously revealed that Gluconobacter oxydans differentiates by forming quantities of intracytoplasmic membranes at the end of exponential growth. It was also shown that the formation of these membranes appears concurrently with an increased rate of polyol oxidation. In the present study, exponential-phase cells devoid of intracytoplasmic membranes were harvested and the quantity of free lipid was determined. This quantity was compared with that extracted from cells harvested 4 and 16 h into the stationary phase that contained intracytoplasmic membranes. Cells harvested 4 and 16 h into the stationary phase contained 58 and 43% more free lipid per 100 mg of cell weight than found in undifferentiated exponential-phase cells. These same cultures were used to compare the quantity of lipid extracted per cell. This analysis revealed 89 and 142% more lipid per cell in 4 and 16 h stationary-phase cells. Further study demonstrated that cells increased in length and decreased in density with time after they entered the stationary phase. We estimated, however, that intracytoplasmic membrane development in G. oxydans is accompanied by a 57 to 62% increase in free-lipid that cannot be attributed to a change in cell size. These results suggest that the traditional expression of extracted lipid per milligram of cellular dry weight should not be used for comparative purposes during differentiation in gram-negative bacteria, unless it is first established that both cell size and cell density remain constant throughout differentiation.", "contents": "Change in quantity of lipids and cell size during intracytoplasmic membrane formation in Gluconobacter oxydans. Electron microscopy previously revealed that Gluconobacter oxydans differentiates by forming quantities of intracytoplasmic membranes at the end of exponential growth. It was also shown that the formation of these membranes appears concurrently with an increased rate of polyol oxidation. In the present study, exponential-phase cells devoid of intracytoplasmic membranes were harvested and the quantity of free lipid was determined. This quantity was compared with that extracted from cells harvested 4 and 16 h into the stationary phase that contained intracytoplasmic membranes. Cells harvested 4 and 16 h into the stationary phase contained 58 and 43% more free lipid per 100 mg of cell weight than found in undifferentiated exponential-phase cells. These same cultures were used to compare the quantity of lipid extracted per cell. This analysis revealed 89 and 142% more lipid per cell in 4 and 16 h stationary-phase cells. Further study demonstrated that cells increased in length and decreased in density with time after they entered the stationary phase. We estimated, however, that intracytoplasmic membrane development in G. oxydans is accompanied by a 57 to 62% increase in free-lipid that cannot be attributed to a change in cell size. These results suggest that the traditional expression of extracted lipid per milligram of cellular dry weight should not be used for comparative purposes during differentiation in gram-negative bacteria, unless it is first established that both cell size and cell density remain constant throughout differentiation."} {"id": "PMID:1254553", "title": "Occurrence of phosphenolpyruvate carboxylase in the extremely thermophilic bacterium Thermus aquaticus.", "content": "In the extreme thermophile Thermus aquaticus, phosphoenolpyruvate carboxylase catalyzes carbon dioxide fixation on the C3 metabolite phosphoenolpyruvate, producing oxaloacetate. In a moderately thermophilic Bacillus species this function is fulfilled by pyruvate carboyxlase. Like several of its mesophilic counterparts, the Thermus enzyme exhibits a requirement for acetyl coenzyme A.", "contents": "Occurrence of phosphenolpyruvate carboxylase in the extremely thermophilic bacterium Thermus aquaticus. In the extreme thermophile Thermus aquaticus, phosphoenolpyruvate carboxylase catalyzes carbon dioxide fixation on the C3 metabolite phosphoenolpyruvate, producing oxaloacetate. In a moderately thermophilic Bacillus species this function is fulfilled by pyruvate carboyxlase. Like several of its mesophilic counterparts, the Thermus enzyme exhibits a requirement for acetyl coenzyme A."} {"id": "PMID:1254554", "title": "Lowered levels of colicin Ia membrane receptors in an Escherichia coli mutant defective in heme biosynthesis.", "content": "Cells of an Escherichia coli mutant defective in heme biosynthesis (hemA) grown under conditions for respiration deficiency (grown in the absence of aminolevulinic acid) have 20% of the number of specific colicin Ia receptors found in cells of the same strain grown under conditions for respiration competency (grown in the presence of aminolevulinic acid).", "contents": "Lowered levels of colicin Ia membrane receptors in an Escherichia coli mutant defective in heme biosynthesis. Cells of an Escherichia coli mutant defective in heme biosynthesis (hemA) grown under conditions for respiration deficiency (grown in the absence of aminolevulinic acid) have 20% of the number of specific colicin Ia receptors found in cells of the same strain grown under conditions for respiration competency (grown in the presence of aminolevulinic acid)."} {"id": "PMID:1254555", "title": "Ubiquity of plasmids in coding for toluene and xylene metabolism in soil bacteria: evidence for the existence of new TOL plasmids.", "content": "Thirteen bacteria have been isolated from nine different soil samples by selective enrichment culture on m-toluate (m-methylbenzoate) minimal medium. Eight of these were classified as Pseudomonas putida, one as a fluorescent Pseudomonas sp., and four as nonfluorescent Pseudomonas sp. All 13 strains appeared to carry TOL plasmids superficially similar to that previously described in P. putida mt-2 in that: (i) all the wild-type strains could utilize toluene, m-xylene, and p-xylene as sole carbon and energy sources, (ii) these growth substrates were metabolized through the corresponding alcohols and aldehydes to benzoate, m-toluate, and p-toluate, respectively, and thence by the divergent meta (or alpha-ketoacid) pathway, and (iii) the isolates could simultaneously and spontaneously lose their ability to utilize the hydrocarbons, alcohols, aldehydes, and acids, particularly during growth on benzoate, giving rise to cured strains which could grow only on benzaldehyde and benzoate of the aromatic substrates by the alternative ortho (or beta-ketoadipate) pathway. Eight of the isolates were able to transfer their TOL plasmids into their own cured strains, but only five were able to transfer them in interstrain conjugation into the cured strains, but only five were able to transfer them in interstrain conjugation into the cured derivative of P. putida mt-2. However, P. putida mt-2 was able to transfer its TOL plasmid into 11 of the cured isolates, and eight of these were able to retransmit this foreign plasmid in intrastrain conjugation with their own cured derivatives. Three of the isolates, MT 14, MT 15, and MT 20, differed significantly from the others in that the wild-type strains dissimilated the p-methyl-substituted substrates poorly, and also, during growth on benzoate, in addition to the cured derivatives, they gave rise to derivatives with a phenotype intermediate between the cured and wild-type strains, the biochemical and genetic nature of which has not been elucidated.", "contents": "Ubiquity of plasmids in coding for toluene and xylene metabolism in soil bacteria: evidence for the existence of new TOL plasmids. Thirteen bacteria have been isolated from nine different soil samples by selective enrichment culture on m-toluate (m-methylbenzoate) minimal medium. Eight of these were classified as Pseudomonas putida, one as a fluorescent Pseudomonas sp., and four as nonfluorescent Pseudomonas sp. All 13 strains appeared to carry TOL plasmids superficially similar to that previously described in P. putida mt-2 in that: (i) all the wild-type strains could utilize toluene, m-xylene, and p-xylene as sole carbon and energy sources, (ii) these growth substrates were metabolized through the corresponding alcohols and aldehydes to benzoate, m-toluate, and p-toluate, respectively, and thence by the divergent meta (or alpha-ketoacid) pathway, and (iii) the isolates could simultaneously and spontaneously lose their ability to utilize the hydrocarbons, alcohols, aldehydes, and acids, particularly during growth on benzoate, giving rise to cured strains which could grow only on benzaldehyde and benzoate of the aromatic substrates by the alternative ortho (or beta-ketoadipate) pathway. Eight of the isolates were able to transfer their TOL plasmids into their own cured strains, but only five were able to transfer them in interstrain conjugation into the cured strains, but only five were able to transfer them in interstrain conjugation into the cured derivative of P. putida mt-2. However, P. putida mt-2 was able to transfer its TOL plasmid into 11 of the cured isolates, and eight of these were able to retransmit this foreign plasmid in intrastrain conjugation with their own cured derivatives. Three of the isolates, MT 14, MT 15, and MT 20, differed significantly from the others in that the wild-type strains dissimilated the p-methyl-substituted substrates poorly, and also, during growth on benzoate, in addition to the cured derivatives, they gave rise to derivatives with a phenotype intermediate between the cured and wild-type strains, the biochemical and genetic nature of which has not been elucidated."} {"id": "PMID:1254556", "title": "Partial purification and characterization of cytidine 5'-diphosphate-diglyceride hydrolase from membranes of Escherichia coli.", "content": "Cytidine 5'-diphosphate (CDP)-diglyceride is hydrolyzed to phosphatidic acid and cytidine 5'-monophosphate by a specific membrane-bound enzyme in cell-free extracts of Escherichia coli. The hydrolase can be extracted from the particulate fraction with Triton X-100 and purified 1,000-fold in the presence of this detergent. Several nucleoside disphosphate diglycerides were synthesized to determine the substrate specificity of the hydrolase. CDP-diglyceride was hydrolyzed preferentially, although uridine 5'-diphosphate-diglyceride, guanosine 5'-diphosphate-diglyceride, and adenosine 5'-diphosphate (ADP)-diglyceride were also slowly hydrolyzed. Surprisingly, the purified enzyme did not catalyze detectable cleavage of deoxy-CDP (dCDP)-diglyceride. The liponucleotide pool of E. coli contains dCDP-diglyceride and CDP-diglyceride in approximately equal amounts (Raetz and Kennedy, 1973). Water-soluble nucleoside pyrophosphates, such as CDP-choline, nicotinamide adenine dinucleotide, or adenosine 5'-triphosphate are not attacked by this specific hydrolase. Hydrolysis of CDP-diglyceride is strongly inhibited by adenosine 5'-monophosphate and by ADP-diglyceride.", "contents": "Partial purification and characterization of cytidine 5'-diphosphate-diglyceride hydrolase from membranes of Escherichia coli. Cytidine 5'-diphosphate (CDP)-diglyceride is hydrolyzed to phosphatidic acid and cytidine 5'-monophosphate by a specific membrane-bound enzyme in cell-free extracts of Escherichia coli. The hydrolase can be extracted from the particulate fraction with Triton X-100 and purified 1,000-fold in the presence of this detergent. Several nucleoside disphosphate diglycerides were synthesized to determine the substrate specificity of the hydrolase. CDP-diglyceride was hydrolyzed preferentially, although uridine 5'-diphosphate-diglyceride, guanosine 5'-diphosphate-diglyceride, and adenosine 5'-diphosphate (ADP)-diglyceride were also slowly hydrolyzed. Surprisingly, the purified enzyme did not catalyze detectable cleavage of deoxy-CDP (dCDP)-diglyceride. The liponucleotide pool of E. coli contains dCDP-diglyceride and CDP-diglyceride in approximately equal amounts (Raetz and Kennedy, 1973). Water-soluble nucleoside pyrophosphates, such as CDP-choline, nicotinamide adenine dinucleotide, or adenosine 5'-triphosphate are not attacked by this specific hydrolase. Hydrolysis of CDP-diglyceride is strongly inhibited by adenosine 5'-monophosphate and by ADP-diglyceride."} {"id": "PMID:1254557", "title": "In vitro system for the synthesis of teichoic acid linked to peptidoglycan.", "content": "A crude cell wall preparation from Staphylococcus aureus H prepared by the method of Mirelman and Sharon (1972) was shown to catalyze the synthesis of polyribitol phosphate linked to the cell wall peptidoglycan. The reaction used cytidine diphosphate (CDP)-ribitol as a substrate and in addition required the presence of CDP-glycerol, uridine diphosphate (UDP)-N-acetyl-D-glucosamine, and adenosine triphosphate. Incubation of radioactive CDP-glycerol with the crude cell wall preparation resulted in the transfer of glycerol phosphate residues to the cell wall; this reaction was greatly stimulated by the presence of UDP-N-acetylglucosamine. These data suggest that polyribitol phosphate is linked to the cell wall peptidoglycan by an oligomer contaning N-acetyl-D-glucosamine and glycerol phosphate.", "contents": "In vitro system for the synthesis of teichoic acid linked to peptidoglycan. A crude cell wall preparation from Staphylococcus aureus H prepared by the method of Mirelman and Sharon (1972) was shown to catalyze the synthesis of polyribitol phosphate linked to the cell wall peptidoglycan. The reaction used cytidine diphosphate (CDP)-ribitol as a substrate and in addition required the presence of CDP-glycerol, uridine diphosphate (UDP)-N-acetyl-D-glucosamine, and adenosine triphosphate. Incubation of radioactive CDP-glycerol with the crude cell wall preparation resulted in the transfer of glycerol phosphate residues to the cell wall; this reaction was greatly stimulated by the presence of UDP-N-acetylglucosamine. These data suggest that polyribitol phosphate is linked to the cell wall peptidoglycan by an oligomer contaning N-acetyl-D-glucosamine and glycerol phosphate."} {"id": "PMID:1254558", "title": "Diminution of outer membrane permeability by Mg2+ in a marine pseudomonad.", "content": "Intact cells of the marine pseudomonad MB-45, in the presence of optimal Mg2+, exhibited little alkaline phosphatase activity as judged by the hydrolysis of p-nitrophenylphosphate. Sonic extracts, in contrast, were rich in this activity. Removal of the loosely bound outer layer did not diminish this crypticity of alkaline phosphatase, but decreasing the concentration of Mg2+ in the suspending medium progressively exposed the alkaline phosphatase. Since MB-45 did not liberate alkaline phosphatase into the surrounding medium even in the absence of Mg2+ and since this enzyme is localized in the periplasmic space, it can be concluded that the crypticity was due to the exclusion of p-nitrophenylphosphate by the outer membrane. Mg2+ is apparently essential for the full expression of this limited permeability.", "contents": "Diminution of outer membrane permeability by Mg2+ in a marine pseudomonad. Intact cells of the marine pseudomonad MB-45, in the presence of optimal Mg2+, exhibited little alkaline phosphatase activity as judged by the hydrolysis of p-nitrophenylphosphate. Sonic extracts, in contrast, were rich in this activity. Removal of the loosely bound outer layer did not diminish this crypticity of alkaline phosphatase, but decreasing the concentration of Mg2+ in the suspending medium progressively exposed the alkaline phosphatase. Since MB-45 did not liberate alkaline phosphatase into the surrounding medium even in the absence of Mg2+ and since this enzyme is localized in the periplasmic space, it can be concluded that the crypticity was due to the exclusion of p-nitrophenylphosphate by the outer membrane. Mg2+ is apparently essential for the full expression of this limited permeability."} {"id": "PMID:1254559", "title": "Distribution and composition of lipopolysaccharides from mycoplasmas.", "content": "Polymeric carbohydrates containing glycerol and fatty acids were isolated from whole cells and membranes of mycoplasmas by hot aqueous phenol extraction and gel filtration. Lipopolysaccharides were found to occur in four species of Acholeplasma, two of Anaeroplasma, and in Mycoplasma neurolyticum. None were detected in Spiroplasma citri or in five species of Mycoplasma. All lipopolysaccharides contained both neutral and N-acylated amino sugars in ratios varying from 1:1 to 3:1. The neutral sugars found in varying distribution were glucose, galactose, and mannose. The amino sugars included fucosamine, an unidentified deoxyhexosamine, galactosamine, and glucosamine. Fucosamine and glucose were the only sugars common to all lipopolysaccharides. The fatty acids were similar to those found in the lipids of each organism.", "contents": "Distribution and composition of lipopolysaccharides from mycoplasmas. Polymeric carbohydrates containing glycerol and fatty acids were isolated from whole cells and membranes of mycoplasmas by hot aqueous phenol extraction and gel filtration. Lipopolysaccharides were found to occur in four species of Acholeplasma, two of Anaeroplasma, and in Mycoplasma neurolyticum. None were detected in Spiroplasma citri or in five species of Mycoplasma. All lipopolysaccharides contained both neutral and N-acylated amino sugars in ratios varying from 1:1 to 3:1. The neutral sugars found in varying distribution were glucose, galactose, and mannose. The amino sugars included fucosamine, an unidentified deoxyhexosamine, galactosamine, and glucosamine. Fucosamine and glucose were the only sugars common to all lipopolysaccharides. The fatty acids were similar to those found in the lipids of each organism."} {"id": "PMID:1254560", "title": "Lipid composition and lipid metabolism of Spiroplasma citri.", "content": "In a horse serum-based medium containing a full complement of fatty acids, cells of Spiroplasma citri were seen to preferentially incorporate palmitic acid. In the same medium, which had a steryl ester-to-sterol ratio of 3.64, a steryl ester-to-sterol ratio of 0.23 was seen in the cells, cholesterol being preferentially incorporated over cholesteryl ester. Like most other mycoplasmas, S. citri was shown to be unable to synthesize fatty acids or esterify cholesterol. The neutral lipids of S. citri grown in a medium containing horse serum consisted of free cholesterol, cholesteryl ester, free fatty acids, triglycerides and diglycerides. All polar lipids were phospholipids, with no glycolipids detected. These phospholipids, which are characteristic of many mycoplasmas, are phosphatidyl glycerol, diphosphatidyl glycerol, and their lyso derivatives. Sphingomyelin was also incorporated when cells were grown on horse serum. A sterol requirement for the growth of S. citri was confirmed using a serum-free medium supplemented with bovine serum albumin, palmitic acid, and various concentrations of sterols dissolved in Tween 80. The addition of palmitic acid stimulated growth but was not essential for growth. S citri was shown to grow best on cholesterol and beta-sitosterol and was able to grow on stigmasterol and ergosterol to a lesser degree. No growth was obtained using mevalonate, deoxycholate, or taurodeoxycholate as an alternative to sterol. S. citri was also able to grow when palmitic acid was replaced with oleic acid, linoleic acid, or linolenic acid. Alterations in the lipid composition of the growth medium and hence in the lipid composition of S. citri induced changes in the characteristic helical morphology of the cells, concurrent with loss of cell viability. Culture, age, and pH were also factors in determining cell morphology and viability.", "contents": "Lipid composition and lipid metabolism of Spiroplasma citri. In a horse serum-based medium containing a full complement of fatty acids, cells of Spiroplasma citri were seen to preferentially incorporate palmitic acid. In the same medium, which had a steryl ester-to-sterol ratio of 3.64, a steryl ester-to-sterol ratio of 0.23 was seen in the cells, cholesterol being preferentially incorporated over cholesteryl ester. Like most other mycoplasmas, S. citri was shown to be unable to synthesize fatty acids or esterify cholesterol. The neutral lipids of S. citri grown in a medium containing horse serum consisted of free cholesterol, cholesteryl ester, free fatty acids, triglycerides and diglycerides. All polar lipids were phospholipids, with no glycolipids detected. These phospholipids, which are characteristic of many mycoplasmas, are phosphatidyl glycerol, diphosphatidyl glycerol, and their lyso derivatives. Sphingomyelin was also incorporated when cells were grown on horse serum. A sterol requirement for the growth of S. citri was confirmed using a serum-free medium supplemented with bovine serum albumin, palmitic acid, and various concentrations of sterols dissolved in Tween 80. The addition of palmitic acid stimulated growth but was not essential for growth. S citri was shown to grow best on cholesterol and beta-sitosterol and was able to grow on stigmasterol and ergosterol to a lesser degree. No growth was obtained using mevalonate, deoxycholate, or taurodeoxycholate as an alternative to sterol. S. citri was also able to grow when palmitic acid was replaced with oleic acid, linoleic acid, or linolenic acid. Alterations in the lipid composition of the growth medium and hence in the lipid composition of S. citri induced changes in the characteristic helical morphology of the cells, concurrent with loss of cell viability. Culture, age, and pH were also factors in determining cell morphology and viability."} {"id": "PMID:1254561", "title": "Production of extracellular ribonuclease by yeasts and yeastlike fungi, and its repression by orthophosphate in species of Cryptococcus and Tremella.", "content": "A strain of Cryptococcus laurentii and a haploid isolate of Tremella foliacea were shown to produce orthophosphate-repressible ribonuclease in liquid culture. Addition of as little as 1 mM K2HPO4, pH 7.0, completely repressed enzyme production by both fungi. The orthophosphate-repressible enzyme was not produced by other species of the two genera tested. These results, together with other findings, suggest a close phylogenetic relationship between Cryptococcus laurentii and Tremella foliacea. The ability of other yeasts and yeastlike fungi to hydrolyze ribonucleic acid in a solid test medium was assessed. Based on the limited number of organisms available for study, extracellular ribonuclease activity was found in species having close affinity to the Basidiomycetes and in yeasts classified in the ascomycetous genera, Endomycopsis, Hansenula, and Kluyveromyces. Other ascomycetous yeasts did not exhibit extracellular ribonuclease.", "contents": "Production of extracellular ribonuclease by yeasts and yeastlike fungi, and its repression by orthophosphate in species of Cryptococcus and Tremella. A strain of Cryptococcus laurentii and a haploid isolate of Tremella foliacea were shown to produce orthophosphate-repressible ribonuclease in liquid culture. Addition of as little as 1 mM K2HPO4, pH 7.0, completely repressed enzyme production by both fungi. The orthophosphate-repressible enzyme was not produced by other species of the two genera tested. These results, together with other findings, suggest a close phylogenetic relationship between Cryptococcus laurentii and Tremella foliacea. The ability of other yeasts and yeastlike fungi to hydrolyze ribonucleic acid in a solid test medium was assessed. Based on the limited number of organisms available for study, extracellular ribonuclease activity was found in species having close affinity to the Basidiomycetes and in yeasts classified in the ascomycetous genera, Endomycopsis, Hansenula, and Kluyveromyces. Other ascomycetous yeasts did not exhibit extracellular ribonuclease."} {"id": "PMID:1254562", "title": "Isolation and characterization of a mutant of Staphylococcus aureus deficient in autolytic activity.", "content": "A mutant of Staphylococcus aureus H (RUS3) uas isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. The rate of autolysis of whole cells and isolated cell walls of RUS3 was less than 10% of the parent strain. In addition, the ability of the crude soluble enzyme isolated from RUS3 to degrade cell walls was negligible compared with the parent strain. The cell wall composition and the generation time of RUS3 were comparable to the parent strain. Unlike S. aureus H, RUS3 grew in clumps and did not undergo cell wall turnover. Both strains exhibited identical kinetics of killing by penicillin G. This may indicate that autolytic enzymes play a role in cell wall turnover and cell separation, but in S. aureus most of the autolytic activity is unrelated to the lethal effect of cell wall antibiotics.", "contents": "Isolation and characterization of a mutant of Staphylococcus aureus deficient in autolytic activity. A mutant of Staphylococcus aureus H (RUS3) uas isolated after mutagenesis with N-methyl-N'-nitro-N-nitrosoguanidine. The rate of autolysis of whole cells and isolated cell walls of RUS3 was less than 10% of the parent strain. In addition, the ability of the crude soluble enzyme isolated from RUS3 to degrade cell walls was negligible compared with the parent strain. The cell wall composition and the generation time of RUS3 were comparable to the parent strain. Unlike S. aureus H, RUS3 grew in clumps and did not undergo cell wall turnover. Both strains exhibited identical kinetics of killing by penicillin G. This may indicate that autolytic enzymes play a role in cell wall turnover and cell separation, but in S. aureus most of the autolytic activity is unrelated to the lethal effect of cell wall antibiotics."} {"id": "PMID:1254563", "title": "Requirement for pantothenate for filament formation by Erwinia carotovora.", "content": "Pantothenate is required for the formation of filaments by Erwinia carotovora. This has been demonstrated for the following division-inhibiting agents: D-serine, D-cycloserine, penicillin, vancomycin, fluoride ion, and ultraviolet light. D-Serine inhibits pantothenate synthesis in an ammonia-glucose or an ammonia-pyruvate medium; therefore, it is necessary to add pantothenate to obtain filament formation in these media, using D-serine as the division-inhibiting agent. Under conditions in which pantothenate synthesis is not inhibited by the agent producing filaments, the need for it for filamentation was shown by the use of salicylate, an inhibitor of endogenous pantothenate synthesis. Evidence is presented that the production of filaments is a specific response to pantothenate, rather than a nonspecific growth stimulation.", "contents": "Requirement for pantothenate for filament formation by Erwinia carotovora. Pantothenate is required for the formation of filaments by Erwinia carotovora. This has been demonstrated for the following division-inhibiting agents: D-serine, D-cycloserine, penicillin, vancomycin, fluoride ion, and ultraviolet light. D-Serine inhibits pantothenate synthesis in an ammonia-glucose or an ammonia-pyruvate medium; therefore, it is necessary to add pantothenate to obtain filament formation in these media, using D-serine as the division-inhibiting agent. Under conditions in which pantothenate synthesis is not inhibited by the agent producing filaments, the need for it for filamentation was shown by the use of salicylate, an inhibitor of endogenous pantothenate synthesis. Evidence is presented that the production of filaments is a specific response to pantothenate, rather than a nonspecific growth stimulation."} {"id": "PMID:1254564", "title": "Metabolism of resorcinylic compounds by bacteria: orcinol pathway in Pseudomonas putida.", "content": "Enrichment cultures yielded two strains of Pseudomonas putida capable of growth with orcinol (3,5-dihydroxytoluene) as the sole source of carbon. Experiments with cell suspensions and cell extracts indicate that orcinol is metabolized by hydroxylation of the benzene ring followed successively by ring cleavage and hydrolyses to give 2 mol of acetate and 1 mol of pyruvate per mol of orcinol as shown: orcinol leads to 2,3,5-trihydroxytoluene leads to 2,4,6-trioxoheptanoate leads to acetate + acetylpyruvate leads to acetate + pyruvate. Evidence for this pathway is based on: (i) high respiratory activities of orcinol-grown cells towards 2,3,5-trihydroxytoluene; (ii) transient accumulation of a quinone, probably 2-hydroxy-6-methyl-1,4-benzoquinone, during grouth with orcinol; (iii) formation of pyruvate and acetate from orcinol, 2,3,5-trihydroxytoluene, and acetylpyruvate catalyzed by extracts of orcinol, but not by succinate-grown cells; (iv) characterization of the product of oxidation of 3-methylcatechol (an analogue of 2,3,5-trihydroxytoluene) showing that oxygenative cleavage occurs between carbons bearing methyl and hydroxyl substituents; (v) transient appearance of a compound having spectral properties similar to those of acetylpyruvate during 2,3,5-trihydroxytoluene oxidation by extracts of orcinol-grown cells. Orcinol hydroxylase exhibits catalytic activity when resorcinol or m-cresol is substituted for orcinol; hydroxyquinol and 3-methylcatechol are substrates for the ring cleavage enzyme 2,3,5-trihydroxytoluene-1,2-oxygenase. The enzymes of this pathway are induced by growth with orcinol but not with glucose or succinate.", "contents": "Metabolism of resorcinylic compounds by bacteria: orcinol pathway in Pseudomonas putida. Enrichment cultures yielded two strains of Pseudomonas putida capable of growth with orcinol (3,5-dihydroxytoluene) as the sole source of carbon. Experiments with cell suspensions and cell extracts indicate that orcinol is metabolized by hydroxylation of the benzene ring followed successively by ring cleavage and hydrolyses to give 2 mol of acetate and 1 mol of pyruvate per mol of orcinol as shown: orcinol leads to 2,3,5-trihydroxytoluene leads to 2,4,6-trioxoheptanoate leads to acetate + acetylpyruvate leads to acetate + pyruvate. Evidence for this pathway is based on: (i) high respiratory activities of orcinol-grown cells towards 2,3,5-trihydroxytoluene; (ii) transient accumulation of a quinone, probably 2-hydroxy-6-methyl-1,4-benzoquinone, during grouth with orcinol; (iii) formation of pyruvate and acetate from orcinol, 2,3,5-trihydroxytoluene, and acetylpyruvate catalyzed by extracts of orcinol, but not by succinate-grown cells; (iv) characterization of the product of oxidation of 3-methylcatechol (an analogue of 2,3,5-trihydroxytoluene) showing that oxygenative cleavage occurs between carbons bearing methyl and hydroxyl substituents; (v) transient appearance of a compound having spectral properties similar to those of acetylpyruvate during 2,3,5-trihydroxytoluene oxidation by extracts of orcinol-grown cells. Orcinol hydroxylase exhibits catalytic activity when resorcinol or m-cresol is substituted for orcinol; hydroxyquinol and 3-methylcatechol are substrates for the ring cleavage enzyme 2,3,5-trihydroxytoluene-1,2-oxygenase. The enzymes of this pathway are induced by growth with orcinol but not with glucose or succinate."} {"id": "PMID:1254565", "title": "Beta-Adrenergic receptor interactions. Characterization of iodohydroxybenzylpindolol as a specific ligand.", "content": "Hydroxybenzylpindolol (HYP) is a specific and highly potent beta-adrenergic antagonist. Monoiodination of HYP produces an equally high affinity inhibitor of binding to and activation of the beta receptor-coupled adenylate cyclase in turkey erythrocyte membranes. Monoiodohydroxybenzylpindolol was isolated by high pressure liquid chromatography. Mass spectroscopy showed that the iodine was contained in the phenolic moiety of the molecule. 125I-HYP was purified in tracer amounts by ion exchange chromatography; specific activities were achieved (1500 to 2000 Ci/mmol) approaching theoretical for 1 mol of iodine/mol of HYP. 125I-HYP interacts with a single stereospecific site with affinity of 4 to 5 X 10(10) M-1 by Scatchard analysis. Maximal binding capacity was 0.2 to 0.3 pmol/mg of membrane protein. If recovery of receptor were complete, this would correspond to 400 to 600 receptor sites per cell. Kinetic analyses of the on and off reactions gave a kinetically derived KA in good agreement with that derived from thermodynamic methods both at 20 degrees and 37 degrees. No evidence is found in these experiments for cooperative interaction of ligands with the receptor system. Iodohydroxybenzylpindolol thus represents a high affinity, high specific activity ligand of established chemical structure which should prove useful in studying the interaction of other blockers and agonists with the beta-adrenergic receptor in this and other biological systems.", "contents": "Beta-Adrenergic receptor interactions. Characterization of iodohydroxybenzylpindolol as a specific ligand. Hydroxybenzylpindolol (HYP) is a specific and highly potent beta-adrenergic antagonist. Monoiodination of HYP produces an equally high affinity inhibitor of binding to and activation of the beta receptor-coupled adenylate cyclase in turkey erythrocyte membranes. Monoiodohydroxybenzylpindolol was isolated by high pressure liquid chromatography. Mass spectroscopy showed that the iodine was contained in the phenolic moiety of the molecule. 125I-HYP was purified in tracer amounts by ion exchange chromatography; specific activities were achieved (1500 to 2000 Ci/mmol) approaching theoretical for 1 mol of iodine/mol of HYP. 125I-HYP interacts with a single stereospecific site with affinity of 4 to 5 X 10(10) M-1 by Scatchard analysis. Maximal binding capacity was 0.2 to 0.3 pmol/mg of membrane protein. If recovery of receptor were complete, this would correspond to 400 to 600 receptor sites per cell. Kinetic analyses of the on and off reactions gave a kinetically derived KA in good agreement with that derived from thermodynamic methods both at 20 degrees and 37 degrees. No evidence is found in these experiments for cooperative interaction of ligands with the receptor system. Iodohydroxybenzylpindolol thus represents a high affinity, high specific activity ligand of established chemical structure which should prove useful in studying the interaction of other blockers and agonists with the beta-adrenergic receptor in this and other biological systems."} {"id": "PMID:1254566", "title": "Beta-Adrenergic receptor interactions. Direct comparison of receptor interaction and biological activity.", "content": "Iodohydroxybenzylpindolol (I-HYP) is a chemically defined, high affinity, high specific activity beta-adrenergic antagonist that interacts with a single site on the turkey erythrocyte membrane. Study of the interaction of agonists, antagonists, and congeners with this site and concomitant alterations in adenylate cyclase activity have been carried out in the presence of high or low concentrations of guanine nucleotide. The results help clarify the relationship between binding and activation or inhibition of adenylate cyclase and the role of guanine nucleotides in modulating this interaction. There is a close correlation between binding constants (KD) for inhibitors determined by analysis of competitive displacement of 125I-HYP from receptor, and apparent affinities (Ki) for inhibition of adenylate cyclase. For activators, however, there is up to a 10-fold difference between KD and apparent affinity (KDapp) for adenylate cyclase activation at low guanine nucleotide concentration (10(-6) M guanylylimidodiphosphate). This difference is virtually abolished by employing higher nucleotide concentrations (10(-5) M guanylylimidodiphosphate) without significantly altering receptor affinity. This suggests that guanine nucleotides act by modulating receptor-enzyme interactions rather than hormone-receptor interactions. Moreover, several beta-adrenergic analogs previously shown to have no effect on adenylate cyclase in the absence of nucleotide, are partial agonists in the presence of 10(-5) M guanylylimidodiphosphate. Parallel analyses for a series of agonists and antagonists for adenylate cyclase activation and receptor interaction show affinities for levorotatory isomers generally 100-fold greater than for dextrorotatory isomers. Thus stereoconfiguration at the beta carbon clearly influences affinity of agonists or antagonists. Affinity is also importantly influenced by the nature of the aromatic ring as well as the N-alkyl group. The complexity of structure-function relationships for these compounds requires a redefinition of structural requirements for beta-adrenergic activity.", "contents": "Beta-Adrenergic receptor interactions. Direct comparison of receptor interaction and biological activity. Iodohydroxybenzylpindolol (I-HYP) is a chemically defined, high affinity, high specific activity beta-adrenergic antagonist that interacts with a single site on the turkey erythrocyte membrane. Study of the interaction of agonists, antagonists, and congeners with this site and concomitant alterations in adenylate cyclase activity have been carried out in the presence of high or low concentrations of guanine nucleotide. The results help clarify the relationship between binding and activation or inhibition of adenylate cyclase and the role of guanine nucleotides in modulating this interaction. There is a close correlation between binding constants (KD) for inhibitors determined by analysis of competitive displacement of 125I-HYP from receptor, and apparent affinities (Ki) for inhibition of adenylate cyclase. For activators, however, there is up to a 10-fold difference between KD and apparent affinity (KDapp) for adenylate cyclase activation at low guanine nucleotide concentration (10(-6) M guanylylimidodiphosphate). This difference is virtually abolished by employing higher nucleotide concentrations (10(-5) M guanylylimidodiphosphate) without significantly altering receptor affinity. This suggests that guanine nucleotides act by modulating receptor-enzyme interactions rather than hormone-receptor interactions. Moreover, several beta-adrenergic analogs previously shown to have no effect on adenylate cyclase in the absence of nucleotide, are partial agonists in the presence of 10(-5) M guanylylimidodiphosphate. Parallel analyses for a series of agonists and antagonists for adenylate cyclase activation and receptor interaction show affinities for levorotatory isomers generally 100-fold greater than for dextrorotatory isomers. Thus stereoconfiguration at the beta carbon clearly influences affinity of agonists or antagonists. Affinity is also importantly influenced by the nature of the aromatic ring as well as the N-alkyl group. The complexity of structure-function relationships for these compounds requires a redefinition of structural requirements for beta-adrenergic activity."} {"id": "PMID:1254567", "title": "Quaternary structure of (Na+ + K+)-dependent adenosine triphosphatase.", "content": "(Na+ + K+)-dependent adenosine triphosphatase (NaK-ATPase) consists of two polypeptide chains, a large polypeptide with a molecular weight of about 100,000, and a sialoglycoprotein with a molecular weight of about 40,000. Cross-linking of purified NaK-ATPase with the (o-phenanthroline)2-cupric ion complex (CP) results in the reversible formation of dimers, trimers, tetramers, and pentamers of the large polypeptide and loss of NaK-ATPase activity. ATPase activity is partially recovered if NaK-ATPase is incubated with beta-mercaptoethanol after treatment with CP. In contrast to these results, if NaK-ATPase is cross-linked in crude canine kidney microsomes, only a dimer of the large polypeptide is formed. No cross-linking of the sialoglycoprotein to the large polypeptide is detected when NaK-ATPase is cross-linked in purified form. However, when NaK-ATPase is reacted with CP in either purified or microsomal form, the sialoglycoprotein cross-links to itself yielding a high molecular weight aggregate. The results show that the functional subunit structure of NaK-ATPase consists of at least two large polypeptides.", "contents": "Quaternary structure of (Na+ + K+)-dependent adenosine triphosphatase. (Na+ + K+)-dependent adenosine triphosphatase (NaK-ATPase) consists of two polypeptide chains, a large polypeptide with a molecular weight of about 100,000, and a sialoglycoprotein with a molecular weight of about 40,000. Cross-linking of purified NaK-ATPase with the (o-phenanthroline)2-cupric ion complex (CP) results in the reversible formation of dimers, trimers, tetramers, and pentamers of the large polypeptide and loss of NaK-ATPase activity. ATPase activity is partially recovered if NaK-ATPase is incubated with beta-mercaptoethanol after treatment with CP. In contrast to these results, if NaK-ATPase is cross-linked in crude canine kidney microsomes, only a dimer of the large polypeptide is formed. No cross-linking of the sialoglycoprotein to the large polypeptide is detected when NaK-ATPase is cross-linked in purified form. However, when NaK-ATPase is reacted with CP in either purified or microsomal form, the sialoglycoprotein cross-links to itself yielding a high molecular weight aggregate. The results show that the functional subunit structure of NaK-ATPase consists of at least two large polypeptides."} {"id": "PMID:1254568", "title": "Chemical and physical properties of an hepatic membrane protein that specifically binds asialoglycoproteins.", "content": "The state of aggregation found in water-soluble preparations of an hepatic membrane protein responsible for the clearance of serum asialoglycoproteins has been shown to result from the self-associating properties of a single oligomeric protein. The smallest functional unit identifiable in aqueous solution possessed an estimated molecular weight of 500,000 with each of the successive components increasing in size by an equal amount to form an oligomeric series bearing an integral ratio of 1:2:3:4:5. The tendency towards self-association was promptly and completely reversed by the addition of Triton X-100 with the concomitant appearance of a single component. Extensive treatment with sodium dodecyl sulfate permitted the identification and isolation of two subunits with estimated molecular weights of 48,000 and 40,000, respectively. Amino acid and carbohydrate analyses revealed both subunits to be glycoproteins with a closely similar, but not identical, composition.", "contents": "Chemical and physical properties of an hepatic membrane protein that specifically binds asialoglycoproteins. The state of aggregation found in water-soluble preparations of an hepatic membrane protein responsible for the clearance of serum asialoglycoproteins has been shown to result from the self-associating properties of a single oligomeric protein. The smallest functional unit identifiable in aqueous solution possessed an estimated molecular weight of 500,000 with each of the successive components increasing in size by an equal amount to form an oligomeric series bearing an integral ratio of 1:2:3:4:5. The tendency towards self-association was promptly and completely reversed by the addition of Triton X-100 with the concomitant appearance of a single component. Extensive treatment with sodium dodecyl sulfate permitted the identification and isolation of two subunits with estimated molecular weights of 48,000 and 40,000, respectively. Amino acid and carbohydrate analyses revealed both subunits to be glycoproteins with a closely similar, but not identical, composition."} {"id": "PMID:1254569", "title": "Phospholipids as ionophores.", "content": "The ionophoretic capabilities of phospholipids have been examined by direct measurement in a Pressman cell of the phospholipid-mediated translocation of cations across an organic phase separating two aqueous phases. Cardiolipin and phosphatidic acid were the most active inonophores among the phospholipids tested, with activities comparable to that of X537A in respect to the translocation of divalent cations. Cardiolipin translocates both divalent and monovalent cations at approximately equal rates. The ionophoretic activity of cardiolipin could be modulated by other phospholipids (inhibition), by butacaine (stimulation), by complexation with cytochrome c (inhibition), and by ruthenium red and lanthanum (inhibition). The rate of translocation of cations mediated by cardiolipin was independent of pH over a wide pH range (5.4 to 8.3). The same general pattern of properties observed for cardiolipin applied to phosphatidic acid except for stimulation by butacaine. Complexation of phospholipid mixtures, such as asolectin or mitochondrial lipid, with reduced cytochrome c, enhanced the ionophoretic capability of these phospholipids by 1 order of magnitude. The complex thus formed has the properties of a polyionophore. The possible physiological significance of this enormous ionophoretic potential of phospholipids is examined.", "contents": "Phospholipids as ionophores. The ionophoretic capabilities of phospholipids have been examined by direct measurement in a Pressman cell of the phospholipid-mediated translocation of cations across an organic phase separating two aqueous phases. Cardiolipin and phosphatidic acid were the most active inonophores among the phospholipids tested, with activities comparable to that of X537A in respect to the translocation of divalent cations. Cardiolipin translocates both divalent and monovalent cations at approximately equal rates. The ionophoretic activity of cardiolipin could be modulated by other phospholipids (inhibition), by butacaine (stimulation), by complexation with cytochrome c (inhibition), and by ruthenium red and lanthanum (inhibition). The rate of translocation of cations mediated by cardiolipin was independent of pH over a wide pH range (5.4 to 8.3). The same general pattern of properties observed for cardiolipin applied to phosphatidic acid except for stimulation by butacaine. Complexation of phospholipid mixtures, such as asolectin or mitochondrial lipid, with reduced cytochrome c, enhanced the ionophoretic capability of these phospholipids by 1 order of magnitude. The complex thus formed has the properties of a polyionophore. The possible physiological significance of this enormous ionophoretic potential of phospholipids is examined."} {"id": "PMID:1254570", "title": "Ribonuclease S-peptide. A model for molecular recognition.", "content": "The relationship of structure to function in the recognition of ribonuclease S-peptide by S-protein was studied by several methods. Liquid phase peptide synthesis was employed to generate analogs of S-peptide in which from 1 to 8 residues were deleted from the NH2-terminal end of the S-peptide. Additional derivatives were made by substitutions in the NH2-terminal three amino acids or by modifying the S-peptide analogs by trifluoroacetylation. The analogs were generated in the following way. S-Peptide was cleaved with chymotrypsin. The fragment obtained, RNase(9-20), was purified and lengthened step by step using liquid phase peptide synthesis. A second set of analogs were prepared by cleavage of CF3CO-S-peptide with elastase and the resulting CF3CO-RNase(7-20), similarly lengthened. The various analogs of S-peptide were tested in their capacity to combine with S-protein and regenerate biological activity as measured by Vmax and Kb. This work shows a positive contribution of every one of the first 8 NH2-terminal residues of S-peptide to the molecular recognition of S-protein in the presence of RNA substrate. Substitution of the first 3 residues by alanine or blocking of the free amino groups decreases recognition, indicating that the original primary structure is the most favorable one.", "contents": "Ribonuclease S-peptide. A model for molecular recognition. The relationship of structure to function in the recognition of ribonuclease S-peptide by S-protein was studied by several methods. Liquid phase peptide synthesis was employed to generate analogs of S-peptide in which from 1 to 8 residues were deleted from the NH2-terminal end of the S-peptide. Additional derivatives were made by substitutions in the NH2-terminal three amino acids or by modifying the S-peptide analogs by trifluoroacetylation. The analogs were generated in the following way. S-Peptide was cleaved with chymotrypsin. The fragment obtained, RNase(9-20), was purified and lengthened step by step using liquid phase peptide synthesis. A second set of analogs were prepared by cleavage of CF3CO-S-peptide with elastase and the resulting CF3CO-RNase(7-20), similarly lengthened. The various analogs of S-peptide were tested in their capacity to combine with S-protein and regenerate biological activity as measured by Vmax and Kb. This work shows a positive contribution of every one of the first 8 NH2-terminal residues of S-peptide to the molecular recognition of S-protein in the presence of RNA substrate. Substitution of the first 3 residues by alanine or blocking of the free amino groups decreases recognition, indicating that the original primary structure is the most favorable one."} {"id": "PMID:1254571", "title": "Assessment of protein turnover in perfused rat liver. Evidence for amino acid compartmentation from differential labeling of free and tRNA-gound valine.", "content": "Total protein synthesis in perfused livers of fed rats was determined by measuring the rate of valine incorporation based on the specific activity of valine attached to tRNA. Rates were not significantly altered when perfusate valine was increased from 0.40 to 5 mM and were similar to values calculated earlier from the specific activity of extracellular valine at a concentration of 15 mM. Overall protein degradation, computed from the sum of the rates of synthesis and the total increase of free intra- and extracellular valine, corresponded closely to the increase of free valine that occurred between 5 and 15 min after the addition of cycloheximide. In the latter experiments advantage was taken of the fact that the previously established suppressive effect of cycloheximide on proteolysis does not begin initially with the inhibition of synthesis, but 15 min later. Thus, the release of valine from 5 to 15 min was assumed to represent rates of protein degradation in effect prior to the addition of cycloheximide. The close agreement found among these independent assessments of protein metabolism thus appears to eliminate much of the previous uncertainty in the quantitation of hepatic protein turnover. In the course of these studies we noted that the specific activity of valyl-tRNA attained steady state values that were intermediate between specific activities of the extracellular and intracellular pools, but appeared to reach a steady state sooner than that of intracellular valine. To evaluate these early events more precisely, the specific activity of valine in tRNA and the intracellular pool was measured in a series of single-pass perfusion experiments where extracellular valine concentration and specific activity were held constant. The intracellular valine specific activity rose with a half-life of 1.2 min. By contrast, the rise in the specific activity of valyl-tRNA was biphasic: the initial phase of the valyl-tRNA curve was rapid, while the second phase had a half-life equal to that of intracellular valine. These data show that at physiological concentrations of valine, valyl-tRNA derives its amino acids from both the extracellular and cytoplasmic pools, and that at least some tRNA is charged by extracellular amino acids before they mix with intracellular amino acid pools, possibly from a precursor pool at or near the cell membrane.", "contents": "Assessment of protein turnover in perfused rat liver. Evidence for amino acid compartmentation from differential labeling of free and tRNA-gound valine. Total protein synthesis in perfused livers of fed rats was determined by measuring the rate of valine incorporation based on the specific activity of valine attached to tRNA. Rates were not significantly altered when perfusate valine was increased from 0.40 to 5 mM and were similar to values calculated earlier from the specific activity of extracellular valine at a concentration of 15 mM. Overall protein degradation, computed from the sum of the rates of synthesis and the total increase of free intra- and extracellular valine, corresponded closely to the increase of free valine that occurred between 5 and 15 min after the addition of cycloheximide. In the latter experiments advantage was taken of the fact that the previously established suppressive effect of cycloheximide on proteolysis does not begin initially with the inhibition of synthesis, but 15 min later. Thus, the release of valine from 5 to 15 min was assumed to represent rates of protein degradation in effect prior to the addition of cycloheximide. The close agreement found among these independent assessments of protein metabolism thus appears to eliminate much of the previous uncertainty in the quantitation of hepatic protein turnover. In the course of these studies we noted that the specific activity of valyl-tRNA attained steady state values that were intermediate between specific activities of the extracellular and intracellular pools, but appeared to reach a steady state sooner than that of intracellular valine. To evaluate these early events more precisely, the specific activity of valine in tRNA and the intracellular pool was measured in a series of single-pass perfusion experiments where extracellular valine concentration and specific activity were held constant. The intracellular valine specific activity rose with a half-life of 1.2 min. By contrast, the rise in the specific activity of valyl-tRNA was biphasic: the initial phase of the valyl-tRNA curve was rapid, while the second phase had a half-life equal to that of intracellular valine. These data show that at physiological concentrations of valine, valyl-tRNA derives its amino acids from both the extracellular and cytoplasmic pools, and that at least some tRNA is charged by extracellular amino acids before they mix with intracellular amino acid pools, possibly from a precursor pool at or near the cell membrane."} {"id": "PMID:1254572", "title": "Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture. Patterns of acetylcholine phosphocholine, and choline phosphoglycerides labeling from (methyl-14C)choline.", "content": "The uptake and metabolism of [14C]choline in dissociated rat brain embryo cell cultures was examined as a function of the extracellular choline concentration. Choline uptake did not follow normal Michaelis-Menten kinetics, but rather exhibited two components with apparent Km of 0.016 mM and 0.96 mM. At low choline concentrations (high affinity uptake) most of the [14C]choline label was present in the phosphocholine fraction prior to the appearance of label in phospholipids. At high choline concentrations (low affinity uptake) a large proportion of the radioactivity was converted into acetylcholine. The dissimilarities between the formation of phosphocholine and acetylcholine as a function of choline concentration might be explained by the existence of two mutually independent enzymatic activities with different Km affinities for choline. Kinetic data augmented by double label studies, suggested that formation of choline phosphoglyceride proceeds entirely via a phosphocholine intermediate. Nearly all radioactivity in the lipid fraction is incorporated into choline phosphoglycerides. A higher turnover rate of choline incorporation into choline phosphoglycerides, accompanied by an increase in the levels of glycerophosphocholine, was observed in older cultures as compared to younger cultures. The metabolic implications of these findings in cultured brain cells in comparison with other in vitro systems are discussed.", "contents": "Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture. Patterns of acetylcholine phosphocholine, and choline phosphoglycerides labeling from (methyl-14C)choline. The uptake and metabolism of [14C]choline in dissociated rat brain embryo cell cultures was examined as a function of the extracellular choline concentration. Choline uptake did not follow normal Michaelis-Menten kinetics, but rather exhibited two components with apparent Km of 0.016 mM and 0.96 mM. At low choline concentrations (high affinity uptake) most of the [14C]choline label was present in the phosphocholine fraction prior to the appearance of label in phospholipids. At high choline concentrations (low affinity uptake) a large proportion of the radioactivity was converted into acetylcholine. The dissimilarities between the formation of phosphocholine and acetylcholine as a function of choline concentration might be explained by the existence of two mutually independent enzymatic activities with different Km affinities for choline. Kinetic data augmented by double label studies, suggested that formation of choline phosphoglyceride proceeds entirely via a phosphocholine intermediate. Nearly all radioactivity in the lipid fraction is incorporated into choline phosphoglycerides. A higher turnover rate of choline incorporation into choline phosphoglycerides, accompanied by an increase in the levels of glycerophosphocholine, was observed in older cultures as compared to younger cultures. The metabolic implications of these findings in cultured brain cells in comparison with other in vitro systems are discussed."} {"id": "PMID:1254573", "title": "Inhibition of glutamate dehydrogenase and malate dehydrogenases by palmitoyl coenzyme A.", "content": "In extension of a previous study with yeast glucose-6-P dehydrogenase (Kawaguchi, A., and Bloch, K. (1974) J. Biol. Chem. 249, 5793-5800), the structural changes accompanying the inhibition of glutamate dehydrogenase and several malate dehydrogenases by palmitoyl-CoA and by sodium dodecyl sulfate have been investigated. Palmitoyl-CoA converts liver glutamate dehydrogenase to enzymatically inactive dimeric subunits (Mr = 1.2 X 10(5)) and tightly binds to the dissociated enzyme. Removal of the inhibitor from the palmitoyl-CoA-dimer complex fails to regenerate enzyme activity. The Ki values for palmitoyl-CoA inhibition of malate dehydrogenases (oxalacetate reduction) are, for the enzyme from pig heart mitochondria, 1.8 muM, 500 muM from pig heart supernatant, and 10 muM from chicken heart supernatant. These inhibitions are readily reversible. Palmitoyl-CoA does not alter the quaternary structure of any of the malate dehydrogenases and binds only weakly to these enzymes. Mitochondrial malate dehydrogenase assayed in the direction malate to oxalacetate is much less sensitive to palmitoyl-CoA, with Ki values of 50 muM at pH 10 and greater than 50 muM at pH 7.4. While the differences in palmitoyl-CoA sensitivity in the forward and backward reactions catalyzed by mitochondrial dehydrogenase are unexplained, a physiological rationale for these differential effects is offered. Sodium dodecyl sulfate dissociates the various dehydrogenases to monomeric subunits in contrast to the more selective effects of palmitoyl-CoA.", "contents": "Inhibition of glutamate dehydrogenase and malate dehydrogenases by palmitoyl coenzyme A. In extension of a previous study with yeast glucose-6-P dehydrogenase (Kawaguchi, A., and Bloch, K. (1974) J. Biol. Chem. 249, 5793-5800), the structural changes accompanying the inhibition of glutamate dehydrogenase and several malate dehydrogenases by palmitoyl-CoA and by sodium dodecyl sulfate have been investigated. Palmitoyl-CoA converts liver glutamate dehydrogenase to enzymatically inactive dimeric subunits (Mr = 1.2 X 10(5)) and tightly binds to the dissociated enzyme. Removal of the inhibitor from the palmitoyl-CoA-dimer complex fails to regenerate enzyme activity. The Ki values for palmitoyl-CoA inhibition of malate dehydrogenases (oxalacetate reduction) are, for the enzyme from pig heart mitochondria, 1.8 muM, 500 muM from pig heart supernatant, and 10 muM from chicken heart supernatant. These inhibitions are readily reversible. Palmitoyl-CoA does not alter the quaternary structure of any of the malate dehydrogenases and binds only weakly to these enzymes. Mitochondrial malate dehydrogenase assayed in the direction malate to oxalacetate is much less sensitive to palmitoyl-CoA, with Ki values of 50 muM at pH 10 and greater than 50 muM at pH 7.4. While the differences in palmitoyl-CoA sensitivity in the forward and backward reactions catalyzed by mitochondrial dehydrogenase are unexplained, a physiological rationale for these differential effects is offered. Sodium dodecyl sulfate dissociates the various dehydrogenases to monomeric subunits in contrast to the more selective effects of palmitoyl-CoA."} {"id": "PMID:1254574", "title": "On the sidedness of membrane phosphorylation by Pi and ATP synthesis during reversal of the Ca2+ pump of sarcoplasmic reticulum vesicles.", "content": "The membrane sidedness of Pi interaction in reactions which characterize reversal of the Ca2+ pump of sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle was investigated. Vesicles previously loaded with calcium [32P]phosphate were incubated with 0.1 mM ADP and different concentrations of nonradioactive Pi. Alternatively, vesicles loaded with nonradioactive calcium phosphate were incubated in a medium containing 32Pi. The rates of Ca2+ efflux and ATP synthesis were siginficantly activated only when Pi was included in the assay medium. Although the Pi contained by the vesicles crosses the membrane at a rate proportional to the Ca2+ efflux, [gamma-32P]ATP was synthesized only when 32Pi interacted with the outer surface of the membrane. Similarly, ATP in equilibrium 32Pi or ITP in equilibrium 32Pi exchange could be measured only when the external pool of Pi was labeled. Both for ATP synthesis and for the ITP in equilibrium Pi exchange reaction, membrane phosphorylation by 32Pi was negligible unless the external pool of Pi was labeled. The ionophore X-537 A increased the rate of Ca2+ efflux but inhibited the synthesis of ATP. During reversal of the Ca2+ pump, Pi apparently interacts with the membrane only at the outer surface, and at a site different from that where Ca2+ crosses the membrane.", "contents": "On the sidedness of membrane phosphorylation by Pi and ATP synthesis during reversal of the Ca2+ pump of sarcoplasmic reticulum vesicles. The membrane sidedness of Pi interaction in reactions which characterize reversal of the Ca2+ pump of sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle was investigated. Vesicles previously loaded with calcium [32P]phosphate were incubated with 0.1 mM ADP and different concentrations of nonradioactive Pi. Alternatively, vesicles loaded with nonradioactive calcium phosphate were incubated in a medium containing 32Pi. The rates of Ca2+ efflux and ATP synthesis were siginficantly activated only when Pi was included in the assay medium. Although the Pi contained by the vesicles crosses the membrane at a rate proportional to the Ca2+ efflux, [gamma-32P]ATP was synthesized only when 32Pi interacted with the outer surface of the membrane. Similarly, ATP in equilibrium 32Pi or ITP in equilibrium 32Pi exchange could be measured only when the external pool of Pi was labeled. Both for ATP synthesis and for the ITP in equilibrium Pi exchange reaction, membrane phosphorylation by 32Pi was negligible unless the external pool of Pi was labeled. The ionophore X-537 A increased the rate of Ca2+ efflux but inhibited the synthesis of ATP. During reversal of the Ca2+ pump, Pi apparently interacts with the membrane only at the outer surface, and at a site different from that where Ca2+ crosses the membrane."} {"id": "PMID:1254575", "title": "Kinetic and equilibrium studies of the reactions of heme-substituted horse heart myoglobins with oxygen and carbon monoxide.", "content": "In order to study the effects of chemical modifications of the vinyl groups of heme on oxygen and carbon monoxide binding to myoglobin, apomyoglobins from horse heart were reconstituted with six different hemins with various side chains. Laser flash photolysis experiments of these reconstituted myoglobins showed that the combination rate constants for oxygen (k') and carbon monoxide (l') were closely related to the electron-attractive properties of the side chains. The k' values obtained in 0.1 M potassium phosphate buffer, pH 7.0, at 20 degrees were 0.83 (meso-), 2.4 (deutero-), 1.1 (reconstituted proto-), 1.2 (native proto-), 1.5 (2-formyl-4-vinyl-), 1.9 (2-vinyl-4-formyl-), and 2.7 X 10(7) M-1 S-1 (2,4-diformylmyoglobins), and the corresponding l' values were 2.8, 18, 4.8, 5.1, 7.1, 15, and 35 X 10(5) M-1 S-1, respectively. These rate constants tend to increase as the electron-withdrawing power of the side chains increases, indicating that reduced electron density of the iron atom of heme in myoglobin favors the combination reaction for both oxygen and carbon monoxide. Equilibrium constants (L) between carbon monoxide and various myoglobins were also determined by measuring the partition coefficients (M) between oxygen and carbon monoxide for the myoglobins, and were also found to be closely related to the electronic properties (pK3 of porphyrin) of the heme side chains. The equilibrium association constants for carbon monoxide thus obtained increased with a decrease in pK3 value of the porphyrin. This order was completely opposite to the case of the oxygen binding reaction. The dissociation rate constants for oxygen (k) and carbon monoxide (l) were calculated from the equilibrium and the combination rate constants. The dissociation rate constants showed a similar characteristic to the combination rate constants and increased with the increase in electron attractivity of heme side chains. The concomitant increase in both the combination and dissociation rate constants with increase in electronegativity of the iron atom suggests that these reactions have different rate determining steps, although such a reaction process is contradictory to the generally accepted concept that in a reversible reaction, both on and off reactions proceed through the same transition state. In the on reaction sigma bond formation appears to be dominant, while in the off reaction eta bond break-up is more important.", "contents": "Kinetic and equilibrium studies of the reactions of heme-substituted horse heart myoglobins with oxygen and carbon monoxide. In order to study the effects of chemical modifications of the vinyl groups of heme on oxygen and carbon monoxide binding to myoglobin, apomyoglobins from horse heart were reconstituted with six different hemins with various side chains. Laser flash photolysis experiments of these reconstituted myoglobins showed that the combination rate constants for oxygen (k') and carbon monoxide (l') were closely related to the electron-attractive properties of the side chains. The k' values obtained in 0.1 M potassium phosphate buffer, pH 7.0, at 20 degrees were 0.83 (meso-), 2.4 (deutero-), 1.1 (reconstituted proto-), 1.2 (native proto-), 1.5 (2-formyl-4-vinyl-), 1.9 (2-vinyl-4-formyl-), and 2.7 X 10(7) M-1 S-1 (2,4-diformylmyoglobins), and the corresponding l' values were 2.8, 18, 4.8, 5.1, 7.1, 15, and 35 X 10(5) M-1 S-1, respectively. These rate constants tend to increase as the electron-withdrawing power of the side chains increases, indicating that reduced electron density of the iron atom of heme in myoglobin favors the combination reaction for both oxygen and carbon monoxide. Equilibrium constants (L) between carbon monoxide and various myoglobins were also determined by measuring the partition coefficients (M) between oxygen and carbon monoxide for the myoglobins, and were also found to be closely related to the electronic properties (pK3 of porphyrin) of the heme side chains. The equilibrium association constants for carbon monoxide thus obtained increased with a decrease in pK3 value of the porphyrin. This order was completely opposite to the case of the oxygen binding reaction. The dissociation rate constants for oxygen (k) and carbon monoxide (l) were calculated from the equilibrium and the combination rate constants. The dissociation rate constants showed a similar characteristic to the combination rate constants and increased with the increase in electron attractivity of heme side chains. The concomitant increase in both the combination and dissociation rate constants with increase in electronegativity of the iron atom suggests that these reactions have different rate determining steps, although such a reaction process is contradictory to the generally accepted concept that in a reversible reaction, both on and off reactions proceed through the same transition state. In the on reaction sigma bond formation appears to be dominant, while in the off reaction eta bond break-up is more important."} {"id": "PMID:1254576", "title": "Control of pyrimidine biosynthesis in human lymphocytes. Inhibitory effect of guanine and guanosine on induction of enzymes for pyrimidine biosynthesis de novo in phytohemagglutinin-stimulated lymphocytes.", "content": "Human peripheral lymphocytes were incubated with Phaseolus vulgaris phytohemagglutinin. The induction of glutamine-utilizing carbamyl phosphate synthetase (EC 2.7.2.5) and aspartate transcarbamylase (EC 2.1.3.2) for pyrimidine biosynthesis de novo and the induction of uridine kinase were observed as described previously (Ito, K., and Uchino, H. (1971) J. Biol. Chem. 246, 4060-4065; Ito, K., and Uchino, H. (1973) J. Biol. Chem. 248, 389-392; Lucas, Z.J. (1967) Science 156, 1237-1240). By the addition of 1 mM guanine to the culture, the induction of the former two enzymes was inhibited, while that of uridine kinase was not, and even accelerated. An increase in the rate of [14C] bicarbonate incorporation into the acid-soluble uridine nucleotides via the de novo pathway for pyrimidine biosynthesis after phytohemagglutinin stimulation was inhibited by guanine, the incorporation rate being almost at the level of the control culture without phytohemagglutinin. Guanosine had a similar effect on pyrimidine biosynthesis. The induction of the three enzymes mentioned above was completely inhibited by adenine (1 mM). Guanine and guanosine seem to have a unique inhibitory effect on the induction of glutamine-utilizing carbamyl phosphate synthetase and aspartate transcarbamylase.", "contents": "Control of pyrimidine biosynthesis in human lymphocytes. Inhibitory effect of guanine and guanosine on induction of enzymes for pyrimidine biosynthesis de novo in phytohemagglutinin-stimulated lymphocytes. Human peripheral lymphocytes were incubated with Phaseolus vulgaris phytohemagglutinin. The induction of glutamine-utilizing carbamyl phosphate synthetase (EC 2.7.2.5) and aspartate transcarbamylase (EC 2.1.3.2) for pyrimidine biosynthesis de novo and the induction of uridine kinase were observed as described previously (Ito, K., and Uchino, H. (1971) J. Biol. Chem. 246, 4060-4065; Ito, K., and Uchino, H. (1973) J. Biol. Chem. 248, 389-392; Lucas, Z.J. (1967) Science 156, 1237-1240). By the addition of 1 mM guanine to the culture, the induction of the former two enzymes was inhibited, while that of uridine kinase was not, and even accelerated. An increase in the rate of [14C] bicarbonate incorporation into the acid-soluble uridine nucleotides via the de novo pathway for pyrimidine biosynthesis after phytohemagglutinin stimulation was inhibited by guanine, the incorporation rate being almost at the level of the control culture without phytohemagglutinin. Guanosine had a similar effect on pyrimidine biosynthesis. The induction of the three enzymes mentioned above was completely inhibited by adenine (1 mM). Guanine and guanosine seem to have a unique inhibitory effect on the induction of glutamine-utilizing carbamyl phosphate synthetase and aspartate transcarbamylase."} {"id": "PMID:1254577", "title": "Assay of protamine messenger RNA from rainbow trout testis.", "content": "A low molecular weight RNA fraction possessing protamine mRNA activity was prepared from rainbow trout testis polysomes. Addition of low molecular weight RNA to a Krebs II ascites S-30 cell-free protein synthesis system strongly stimulated [14C]arginine incorporation into acid-insoluble material. This stimulation was completely abolished by 10-4 M aurintricarboxylic acid, an inhibitor of eukaryotic protein synthesis at the level of initiation. Starch gel electrophoresis showed that labeled arginine was incorporated in vitro into products identical with both authentic protamine and histones as found previously (Gilmour, R. S., and Dixon, G. H. (1972) J. Biol. Chem. 247, 4621-4627). The 4 to 6 S RNA fraction, isolated from the polysomal low molecular weight RNA by sucrose gradient fractionation, enhanced the incorporation of [14C]arginine into acid-insoluble material and when this product was examined by starch gel electrophoresis, it co-migrated with authentic rainbow trout protamine.", "contents": "Assay of protamine messenger RNA from rainbow trout testis. A low molecular weight RNA fraction possessing protamine mRNA activity was prepared from rainbow trout testis polysomes. Addition of low molecular weight RNA to a Krebs II ascites S-30 cell-free protein synthesis system strongly stimulated [14C]arginine incorporation into acid-insoluble material. This stimulation was completely abolished by 10-4 M aurintricarboxylic acid, an inhibitor of eukaryotic protein synthesis at the level of initiation. Starch gel electrophoresis showed that labeled arginine was incorporated in vitro into products identical with both authentic protamine and histones as found previously (Gilmour, R. S., and Dixon, G. H. (1972) J. Biol. Chem. 247, 4621-4627). The 4 to 6 S RNA fraction, isolated from the polysomal low molecular weight RNA by sucrose gradient fractionation, enhanced the incorporation of [14C]arginine into acid-insoluble material and when this product was examined by starch gel electrophoresis, it co-migrated with authentic rainbow trout protamine."} {"id": "PMID:1254578", "title": "Purification and properties of biologically active rainbow trout testis protamine mRNA.", "content": "At least two classes of protamine mRNA are present in both trout testis polysomal RNA and RNA from the postribosomal supernatant fraction of trout testis hormogenate both of which direct the synthesis of protamine in a Krebs II ascites S-30. One contains poly(A) tracts and the other is devoid of poly(A). Sucrose gradient analyses showed that the poly(A) containing protamine mRNA (poly(A) (+)) sedimented IN THE 6 S region with a shoulder in the 4 S region while the protamine mRNA devoid of poly(A) (poly(A) (-)) appeared to sediment at about 4 S and could not be resolved from tRNA. Analysis of the poly(A) (+) protamine mRNA by boundary sedimentation in an analytical ultracentrifuge showed a sedimentation coefficient of 5.7 S, a value which gives rise to an estimate of 165 to 170 nucleotides per molecule. The poly(A) (+) protamine mRNA migrated as a single species in formamide-containing polyacrylamide gels and its mobility in relation to markers of tRNA (4 S) and 5 S RNA was consistent with its sedimentation velocity of 6 S. The RNA present in the major band on an aqueous polyacrylamide gel was extracted and shown to code for protamine in a wheat germ cell-free system.", "contents": "Purification and properties of biologically active rainbow trout testis protamine mRNA. At least two classes of protamine mRNA are present in both trout testis polysomal RNA and RNA from the postribosomal supernatant fraction of trout testis hormogenate both of which direct the synthesis of protamine in a Krebs II ascites S-30. One contains poly(A) tracts and the other is devoid of poly(A). Sucrose gradient analyses showed that the poly(A) containing protamine mRNA (poly(A) (+)) sedimented IN THE 6 S region with a shoulder in the 4 S region while the protamine mRNA devoid of poly(A) (poly(A) (-)) appeared to sediment at about 4 S and could not be resolved from tRNA. Analysis of the poly(A) (+) protamine mRNA by boundary sedimentation in an analytical ultracentrifuge showed a sedimentation coefficient of 5.7 S, a value which gives rise to an estimate of 165 to 170 nucleotides per molecule. The poly(A) (+) protamine mRNA migrated as a single species in formamide-containing polyacrylamide gels and its mobility in relation to markers of tRNA (4 S) and 5 S RNA was consistent with its sedimentation velocity of 6 S. The RNA present in the major band on an aqueous polyacrylamide gel was extracted and shown to code for protamine in a wheat germ cell-free system."} {"id": "PMID:1254579", "title": "Purification of and mechanism studies on citrate synthase. Use of biospecific adsorption-elution techniques.", "content": "Citrate synthases from animal tissues were found to bind to Sepharose-\"ATP.\" A pure preparation of citrate synthase was obtained from a crude fraction of rat heart by the specific elution of the enzyme from the Sepharose-\"ATP\" with the dead end complex-forming substrates, oxalacetate and CoA. The proposed mechanisms of citrate synthase, obtained from steady state kinetics, were examined in light of the elution pattern of the enzyme obtained using combinations of substrates and substrate analogs.", "contents": "Purification of and mechanism studies on citrate synthase. Use of biospecific adsorption-elution techniques. Citrate synthases from animal tissues were found to bind to Sepharose-\"ATP.\" A pure preparation of citrate synthase was obtained from a crude fraction of rat heart by the specific elution of the enzyme from the Sepharose-\"ATP\" with the dead end complex-forming substrates, oxalacetate and CoA. The proposed mechanisms of citrate synthase, obtained from steady state kinetics, were examined in light of the elution pattern of the enzyme obtained using combinations of substrates and substrate analogs."} {"id": "PMID:1254580", "title": "Triacylglycerol synthesis in isolated fat cells. An effect of insulin on microsomal fatty acid coenzyme A ligase activity.", "content": "Fatty acid CoA ligase (AMP) (EC 6.2.1.3) specific activity was increased approximately 2-fold in microsomes prepared from isolated rat fat cells incubated with 400 microunits of insulin/ml (2.9 nM) for 45 to 60 min compared to paired controls using an assay based on the conversion of [3H]oleic acid to [3H]oleoyl-CoA. Similar insulin-dependent increases in microsomal fatty acid CoA ligase specific activities were observed using an assay based on the conversion of [3H]CoA to fatty acyl-[3H]CoA. Fatty acid CoA ligase activity was predominately (about 80%) associated with the microsomal fraction. The insulin-dependent increase in microsomal fatty acid CoA ligase specific activity was maximal in 2 to 5 min at 400 microunits/ml. At 10 min, 80 to 100 microunits of insulin/ml caused a maximal increase in fatty acid CoA ligase specific activity. Similar apparent Km values for ATP, CoA, and fatty acid were observed for fatty acid CoA ligase activity in microsomal preparations from control and insulin-exposed cells. These data suggest that fatty acid CoA ligase activity is regulated in adipose tissue by insulin. Such regulation may serve to promote the capture of fatty acid and thereby, triacylglycerol synthesis in adipose tissue.", "contents": "Triacylglycerol synthesis in isolated fat cells. An effect of insulin on microsomal fatty acid coenzyme A ligase activity. Fatty acid CoA ligase (AMP) (EC 6.2.1.3) specific activity was increased approximately 2-fold in microsomes prepared from isolated rat fat cells incubated with 400 microunits of insulin/ml (2.9 nM) for 45 to 60 min compared to paired controls using an assay based on the conversion of [3H]oleic acid to [3H]oleoyl-CoA. Similar insulin-dependent increases in microsomal fatty acid CoA ligase specific activities were observed using an assay based on the conversion of [3H]CoA to fatty acyl-[3H]CoA. Fatty acid CoA ligase activity was predominately (about 80%) associated with the microsomal fraction. The insulin-dependent increase in microsomal fatty acid CoA ligase specific activity was maximal in 2 to 5 min at 400 microunits/ml. At 10 min, 80 to 100 microunits of insulin/ml caused a maximal increase in fatty acid CoA ligase specific activity. Similar apparent Km values for ATP, CoA, and fatty acid were observed for fatty acid CoA ligase activity in microsomal preparations from control and insulin-exposed cells. These data suggest that fatty acid CoA ligase activity is regulated in adipose tissue by insulin. Such regulation may serve to promote the capture of fatty acid and thereby, triacylglycerol synthesis in adipose tissue."} {"id": "PMID:1254581", "title": "Identification and subcellular distribution of adipocyte peptides and phosphopeptides.", "content": "Subcellular fractions of high purity (including plasma membrane, endoplasmic reticulum, mitochondria, nuclei, and cytoplasm) were prepared from isolated adipocytes, and the peptide components were examined by detergent gel electrophoresis. Each fraction except the endoplasmic reticulum exhibited a unique and reproducible complement of major peptides. Although the endoplasmic reticulum was distinctive in its enzymic markers, its peptide components showed striking homologies with certain species in the plasma membrane and cytoplasm. The two major adipocyte glycopeptides appear to be contained in the plasma membrane, inasmuch as they followed the distribution of 5'-nucleotidase. Incubation of adipocytes with extracellular 32Pi led to a uniform rate of incorporation of 32P into cellular peptides, with steady-state incorporation reached by 2 hours. Plasma membrane, mitochondria, nuclei, and cytoplasm all contained a distinctive complement of from two to five major phosphopeptides of different molecular weights. The majority of endoplasmic reticulum phosphopeptides exhibited molecular weights closely similar to those of certain species in the plasma membrane and cytoplasm. The phosphopeptides of the plasma membrane exhibited the highest absolute 32P incorporation of all phosphopeptides, next was the single major mitochondiral phosphopeptide. All fractions except the mitochondria contained, in addition to the few major phosphopeptides, numerous minor 32P-labeled phosphopeptides.", "contents": "Identification and subcellular distribution of adipocyte peptides and phosphopeptides. Subcellular fractions of high purity (including plasma membrane, endoplasmic reticulum, mitochondria, nuclei, and cytoplasm) were prepared from isolated adipocytes, and the peptide components were examined by detergent gel electrophoresis. Each fraction except the endoplasmic reticulum exhibited a unique and reproducible complement of major peptides. Although the endoplasmic reticulum was distinctive in its enzymic markers, its peptide components showed striking homologies with certain species in the plasma membrane and cytoplasm. The two major adipocyte glycopeptides appear to be contained in the plasma membrane, inasmuch as they followed the distribution of 5'-nucleotidase. Incubation of adipocytes with extracellular 32Pi led to a uniform rate of incorporation of 32P into cellular peptides, with steady-state incorporation reached by 2 hours. Plasma membrane, mitochondria, nuclei, and cytoplasm all contained a distinctive complement of from two to five major phosphopeptides of different molecular weights. The majority of endoplasmic reticulum phosphopeptides exhibited molecular weights closely similar to those of certain species in the plasma membrane and cytoplasm. The phosphopeptides of the plasma membrane exhibited the highest absolute 32P incorporation of all phosphopeptides, next was the single major mitochondiral phosphopeptide. All fractions except the mitochondria contained, in addition to the few major phosphopeptides, numerous minor 32P-labeled phosphopeptides."} {"id": "PMID:1254582", "title": "Subcellular localization of nerve growth factor receptors. Thirteen-day chick embryo brain.", "content": "The subcellular location of the specific binding sites of nerve growth factor (NGF) as judged by binding of the 125I-labeled protein in 13-day chick embryo brain, has been examined. The homogenized tissue was separated into four fractions, P1, P2, P3, and S, by differential centrifugation. Fraction P2, which contained the majority of the specific 125I-NGF binding, was further separated by discontinuous sucrose density gradient centrifugation into three fractions. Fraction B contains many synaptosome-like structures, which, when derived from adult brain, result from the shearing off and resealing of synaptic terminals. This fraction contained 65% of the specific 125I-NGF binding of P2. Following hypoosmotic lysis by water, Fraction B was separated into seven fractions, O, D, E, F, G, H, and I, by discontinuous sucrose density gradient centrifugation. The specific 125I-NGF binding was localized with the denser fractions, G, H, and I, with about a 10-fold purification as compared to the original homogenate. However, only 65% of the binding of Fraction B was found in the sum of the tertiary fractions, indicating that some loss of specific binding accompanied the lysis. By means of marker enzymes and macromolecules, as well as electron microscopy, it was determined that the distribution of cellular components of embryonic tissue in this fractionation technique is very similar to that observed for adult brain tissue. Thus, the properties of the NGF receptors determined in whole brain, which are remarkably similar to those found in peripheral neurons, are the properties of the receptors that appear to be located in the developing synaptosomal structures.", "contents": "Subcellular localization of nerve growth factor receptors. Thirteen-day chick embryo brain. The subcellular location of the specific binding sites of nerve growth factor (NGF) as judged by binding of the 125I-labeled protein in 13-day chick embryo brain, has been examined. The homogenized tissue was separated into four fractions, P1, P2, P3, and S, by differential centrifugation. Fraction P2, which contained the majority of the specific 125I-NGF binding, was further separated by discontinuous sucrose density gradient centrifugation into three fractions. Fraction B contains many synaptosome-like structures, which, when derived from adult brain, result from the shearing off and resealing of synaptic terminals. This fraction contained 65% of the specific 125I-NGF binding of P2. Following hypoosmotic lysis by water, Fraction B was separated into seven fractions, O, D, E, F, G, H, and I, by discontinuous sucrose density gradient centrifugation. The specific 125I-NGF binding was localized with the denser fractions, G, H, and I, with about a 10-fold purification as compared to the original homogenate. However, only 65% of the binding of Fraction B was found in the sum of the tertiary fractions, indicating that some loss of specific binding accompanied the lysis. By means of marker enzymes and macromolecules, as well as electron microscopy, it was determined that the distribution of cellular components of embryonic tissue in this fractionation technique is very similar to that observed for adult brain tissue. Thus, the properties of the NGF receptors determined in whole brain, which are remarkably similar to those found in peripheral neurons, are the properties of the receptors that appear to be located in the developing synaptosomal structures."} {"id": "PMID:1254583", "title": "Carbohydrate composition of bovine rhodopsin.", "content": "The carbohydrate content of bovine rhodopsin was investigated and found to be different from previously reported values. Rod outer segments were isolated from dark-adapted bovine retinas by sucrose flotation and purified by sucrose density contrifugation. Rhodopsin was extracted with detergents and purified by chromatographic procedures involving calcium phosphate/celite chromatography followed by affinity chromatograpy on concanavalin A-Sepharose (or in some cases, gel filtration on agarose). Purified preparations of rhodopsin had A278/A498 ratios of 1.6 to 2.0. After treatment of the rhodopsin with chloroform/methanol (2/1) to remove lipids and detergents, the carbohydrate content was measured by gas-liquid chromatography, colorimetric and enzymatic analyses, paper chromatography, and electrophoresis. Rhodopsin was found to have about 9 mol of mannose and 5 mol of glucosamine per mol of visual pigment. A molar ratio of mannose/glucosamine of about 2 was also found in samples of rhodopsin obtained from two other laboratories. The amino acid analysis was similar to previously published values.", "contents": "Carbohydrate composition of bovine rhodopsin. The carbohydrate content of bovine rhodopsin was investigated and found to be different from previously reported values. Rod outer segments were isolated from dark-adapted bovine retinas by sucrose flotation and purified by sucrose density contrifugation. Rhodopsin was extracted with detergents and purified by chromatographic procedures involving calcium phosphate/celite chromatography followed by affinity chromatograpy on concanavalin A-Sepharose (or in some cases, gel filtration on agarose). Purified preparations of rhodopsin had A278/A498 ratios of 1.6 to 2.0. After treatment of the rhodopsin with chloroform/methanol (2/1) to remove lipids and detergents, the carbohydrate content was measured by gas-liquid chromatography, colorimetric and enzymatic analyses, paper chromatography, and electrophoresis. Rhodopsin was found to have about 9 mol of mannose and 5 mol of glucosamine per mol of visual pigment. A molar ratio of mannose/glucosamine of about 2 was also found in samples of rhodopsin obtained from two other laboratories. The amino acid analysis was similar to previously published values."} {"id": "PMID:1254584", "title": "Inactivation of phosphorylase b by potassium ferrate, a new reactive analogue of the phosphate group.", "content": "Rabbit muscle phosphorylase b reacts with the phosphate-like reagent potassium ferrate, K2FeO4, a potent oxidizing agent. The reaction results in inactivation of the enzyme and abolition of the ability of the enzyme to bind 5'-AMP. Activating and nonactivating nucleotides which bind at the 5'-AMP binding site such as 5'-AMP, 2'-AMP, 3'-AMP, and 5'-IMP substantially protect the enzyme from inactivation by ferrate. One to two residues of tyrosine and approximately 1 residue of cysteine are modified by ferrate under the conditions employed. Tyrosine is protected by 5-AMP, whereas cysteine is not. The tyrosine modification is suggested as the inactivating chemical reaction. The location of the inactivating reaction is suggested to be in or near the 5'-AMP binding site. The structural and chemical properties of ferrate ion are discussed and compared to those of phosphate. Ferrate ion may be a reagent useful for phosphate group binding site-directed modification of proteins.", "contents": "Inactivation of phosphorylase b by potassium ferrate, a new reactive analogue of the phosphate group. Rabbit muscle phosphorylase b reacts with the phosphate-like reagent potassium ferrate, K2FeO4, a potent oxidizing agent. The reaction results in inactivation of the enzyme and abolition of the ability of the enzyme to bind 5'-AMP. Activating and nonactivating nucleotides which bind at the 5'-AMP binding site such as 5'-AMP, 2'-AMP, 3'-AMP, and 5'-IMP substantially protect the enzyme from inactivation by ferrate. One to two residues of tyrosine and approximately 1 residue of cysteine are modified by ferrate under the conditions employed. Tyrosine is protected by 5-AMP, whereas cysteine is not. The tyrosine modification is suggested as the inactivating chemical reaction. The location of the inactivating reaction is suggested to be in or near the 5'-AMP binding site. The structural and chemical properties of ferrate ion are discussed and compared to those of phosphate. Ferrate ion may be a reagent useful for phosphate group binding site-directed modification of proteins."} {"id": "PMID:1254585", "title": "Partial puridication of a membrane protein from human erythrocytes involved in glucose transport.", "content": "In an attempt to determine which membrane proteins are essential to the stereospecific uptake of D-glucose, isolated human erythrocyte membranes were exposed to a variety of reagents capable of selectively extracting various membrane proteins. These reagents included EDTA, lithium 3,5-diiodosalicylate, sodium iodide, and 2,3-dimethylmaleic anhydride. Selective elution of spectrin and Components 2.1, 2.2, 2.3, 4.1, 4.2, 5, and 6 representing 65% of the ghost protein has no effect on the uptake of D-glucose. All of the sugar transport proteins are associated with a membrane residue consisting of the proteins of Bands 3, 4.5, and 7, the periodic acid-Schiff-sensitive glycoproteins, and ghost phospholipids. Specific cross-linking of the proteins of Band 3 of ghosts by the catalyzed oxidation of intrinsic sulfhydryl groups with the o-phenanthroline-cupric ion complex inhibits D-glucose uptake and alters the relative electrophoretic mobility of Band 3 proteins in sodium dodecyl sulfate-polyacrylamide-agarose gels. This uptake activity and the relative mobility of Band 3 proteins are recovered upon reversal of the cross-linking reaction by reduction with 2-mercaptoethanol. These results and other observations indicate that the D-glucose transport protein is an intrinsic component of the hydrophobic structure of the erythrocyte membrane and may be associated with the proteins of Band 3 which are glycoproteins spanning the membrane bilayer. It is proposed that D-glucose transport occurs through a water-filled channel formed by specific subunit aggregates of the transport proteins in the erythrocyte membrane rather than by rotation of the protein within the plane of the membrane.", "contents": "Partial puridication of a membrane protein from human erythrocytes involved in glucose transport. In an attempt to determine which membrane proteins are essential to the stereospecific uptake of D-glucose, isolated human erythrocyte membranes were exposed to a variety of reagents capable of selectively extracting various membrane proteins. These reagents included EDTA, lithium 3,5-diiodosalicylate, sodium iodide, and 2,3-dimethylmaleic anhydride. Selective elution of spectrin and Components 2.1, 2.2, 2.3, 4.1, 4.2, 5, and 6 representing 65% of the ghost protein has no effect on the uptake of D-glucose. All of the sugar transport proteins are associated with a membrane residue consisting of the proteins of Bands 3, 4.5, and 7, the periodic acid-Schiff-sensitive glycoproteins, and ghost phospholipids. Specific cross-linking of the proteins of Band 3 of ghosts by the catalyzed oxidation of intrinsic sulfhydryl groups with the o-phenanthroline-cupric ion complex inhibits D-glucose uptake and alters the relative electrophoretic mobility of Band 3 proteins in sodium dodecyl sulfate-polyacrylamide-agarose gels. This uptake activity and the relative mobility of Band 3 proteins are recovered upon reversal of the cross-linking reaction by reduction with 2-mercaptoethanol. These results and other observations indicate that the D-glucose transport protein is an intrinsic component of the hydrophobic structure of the erythrocyte membrane and may be associated with the proteins of Band 3 which are glycoproteins spanning the membrane bilayer. It is proposed that D-glucose transport occurs through a water-filled channel formed by specific subunit aggregates of the transport proteins in the erythrocyte membrane rather than by rotation of the protein within the plane of the membrane."} {"id": "PMID:1254586", "title": "Studies on the mechanism of 3-ketosphinganine synthetase.", "content": "The biosynthesis of sphinganine and 4-D-hydroxysphinganine was studied in rat liver microsomes and whole cells of yeast (Hansenula ciferri). It was shown in both cases that the condensation of [2,3,3-2H3]serine and palmitic acid yielded long chain bases containing only two deuterium atoms, both of which were located on the terminal (C-1) carbon atom by combined gas-liquid chromatography/mass spectrometry. When the reaction with the liver microsomal system was carried out in 2H2O with the protium species of serine, the sphinganine contained a deuterium atom on C-2. These results suggest that the synthesis of 3-ketosphinganine involves the replacement of the alpha-hydrogen atom and the carboxyl group of serine by a proton from the medium and a palmitoyl group, rather than a previously proposed mechanism in which the alpha-hydrogen of serine is retained. Some stereochemical requirements of 3-ketosphinganine synthetase are discussed.", "contents": "Studies on the mechanism of 3-ketosphinganine synthetase. The biosynthesis of sphinganine and 4-D-hydroxysphinganine was studied in rat liver microsomes and whole cells of yeast (Hansenula ciferri). It was shown in both cases that the condensation of [2,3,3-2H3]serine and palmitic acid yielded long chain bases containing only two deuterium atoms, both of which were located on the terminal (C-1) carbon atom by combined gas-liquid chromatography/mass spectrometry. When the reaction with the liver microsomal system was carried out in 2H2O with the protium species of serine, the sphinganine contained a deuterium atom on C-2. These results suggest that the synthesis of 3-ketosphinganine involves the replacement of the alpha-hydrogen atom and the carboxyl group of serine by a proton from the medium and a palmitoyl group, rather than a previously proposed mechanism in which the alpha-hydrogen of serine is retained. Some stereochemical requirements of 3-ketosphinganine synthetase are discussed."} {"id": "PMID:1254587", "title": "Leucine aminopeptidase (bovine lens). The relative binding of cobalt and zinc to leucine aminopeptidase and the effect of cobalt substitution on specific activity.", "content": "Prolonged incubation of zinc-zinc leucine aminopeptidase (bovine lens) (EC 3.4.1.1) with 0.05 M CoCl2 and M KCl in 0.2 M N-ethylmorpholine-HCl at pH 7.5 and 37 degrees yields an active enzyme in which 2 g atoms of Co2+ per 54,000 dalton subunit have replaced the Zn2+. Incubation of cobalt-cobalt leucine aminopeptidase with various AnCl2 concentrations or zinc-zinc leucine aminopeptidase with various CoCl2 concentrations in M KCl and 0.2 M N-ethylmorpholine-HCl at pH 7.5 and 37 degrees demonstrates that Co2+ and Zn2+ compete reversibly for two independent binding sites per subunit for which the ratio of the association constants for Zn2+ and Co2+ (1KZn:1KCo = 1KZn/Co; 2KZn:2KCo = 2KZn/Co) are 115 and 15.9 for sites 1 and 2, respectively. The specific activities of the various species of enzyme with 2 mM L-leucine p-nitroanilide as substrate in 0.2 M N-ethylmorpholine-HCl and 0.01 M NaHCO3 at pH 7.5 are estimated to be (in micromoles per min per mg) 0.043 for the zinc-zinc. 0.039 for the zinc-cobalt, 0.541 for the cobalt-zinc, and 0.536 for the cobalt-cobalt forms, which implies that activity is affected only when cobalt is substituted at site 1, the \"activation site.\" The site, at which cobalt substitution has no effect on activity, is designated the \"structural site.\" The value of Km for cobalt-cobalt leucine aminopeptidase with L-leucine p-nitroanilide as substrate in 0.2 M N-ethylmorpholine-HCl at pH 7.5 containing 0.01 M NaHCO3 at 30 degrees is 0.52 mM while Vmax is 0.90 mumol per min per mg. In the additional presence of 1 M KCl, Km is 0.19 mM while Vmax is 0.68 mumol per min per mg.", "contents": "Leucine aminopeptidase (bovine lens). The relative binding of cobalt and zinc to leucine aminopeptidase and the effect of cobalt substitution on specific activity. Prolonged incubation of zinc-zinc leucine aminopeptidase (bovine lens) (EC 3.4.1.1) with 0.05 M CoCl2 and M KCl in 0.2 M N-ethylmorpholine-HCl at pH 7.5 and 37 degrees yields an active enzyme in which 2 g atoms of Co2+ per 54,000 dalton subunit have replaced the Zn2+. Incubation of cobalt-cobalt leucine aminopeptidase with various AnCl2 concentrations or zinc-zinc leucine aminopeptidase with various CoCl2 concentrations in M KCl and 0.2 M N-ethylmorpholine-HCl at pH 7.5 and 37 degrees demonstrates that Co2+ and Zn2+ compete reversibly for two independent binding sites per subunit for which the ratio of the association constants for Zn2+ and Co2+ (1KZn:1KCo = 1KZn/Co; 2KZn:2KCo = 2KZn/Co) are 115 and 15.9 for sites 1 and 2, respectively. The specific activities of the various species of enzyme with 2 mM L-leucine p-nitroanilide as substrate in 0.2 M N-ethylmorpholine-HCl and 0.01 M NaHCO3 at pH 7.5 are estimated to be (in micromoles per min per mg) 0.043 for the zinc-zinc. 0.039 for the zinc-cobalt, 0.541 for the cobalt-zinc, and 0.536 for the cobalt-cobalt forms, which implies that activity is affected only when cobalt is substituted at site 1, the \"activation site.\" The site, at which cobalt substitution has no effect on activity, is designated the \"structural site.\" The value of Km for cobalt-cobalt leucine aminopeptidase with L-leucine p-nitroanilide as substrate in 0.2 M N-ethylmorpholine-HCl at pH 7.5 containing 0.01 M NaHCO3 at 30 degrees is 0.52 mM while Vmax is 0.90 mumol per min per mg. In the additional presence of 1 M KCl, Km is 0.19 mM while Vmax is 0.68 mumol per min per mg."} {"id": "PMID:1254588", "title": "Human placental 3beta-hydroxysteroid dehydrogenase: delta5-isomerase. Demonstration of an intermediate in the conversion of 3beta-hydroxypregn-5-en-20-one to pregn-4-ene-3,20-dione.", "content": "3beta-Hydroxypregn-5-en-20-one (pregnenolone) and NAD+ were incubated with a solubilized preparation of the coupled enzyme 3beta-hydroxysteroid:NAD(P) oxidoreductase-3-ketosteroid delta4,delta5-isomerase (3beta-hydroxysteroid dehydrogenase: delta5-isomerase) from the mitochondrial fraction of human placenta. Unconverted pregnenolone, pregn-4-ene-3,20-dione (rogesterone), and a small but detectable amount of pregn-5-ene-3,20-dione were isolated from the medium by Sephadex LH-20 chromomatography. The identification of pregn-5-ene-3,20-dione, confirmed by mass fragmentography, has provided the first direct evidence for the formation of the hypothetical delta5,3-ketone intermediate in the conversion of pregnenolone to progesterone. When tritium-labeled pregnenolone and [4-14C]pregnenolone were incubated simultaneously the 3H:14C ratio in isolated pregn-5-ene-3,20-dione was 4.6 times greater than in isolated progesterone and pregnenolone, indicating a kinetic isotope effect in the enzymatic isomerization of tritium-labeled pregn-5-ene-3,20-dione. Exposure of the enzyme to two steroids which inhibit the overall enzyme reaction, 2alpha-cyano-17beta-hydroxy-4,4,17alpha-trimethylandrost-5-en-3-one (cyanoketone) and 3-hydroxyestra-1,3,5(10),6,8-pentaen-17-one (equilenin), increased the relative yield of labeled pregn-5-ene-3,20-dione as well as the recovery of radioactivity remaining as unconverted pregnenolone, suggesting that both the dehydrogenase and isomerase activities were inhibited. Exposure of the enzyme to equilenin increased the ratio of isolated pregn-5-ene-3,20-dione radioactivity to progesterone radioactivity as progesterone synthesis was inhibited. Equilenin also diminished the tritium isotope effect on the isomerase reaction. Both findings suggest that it is possible to inhibit the isomerase to a greater extent than the dehydrogenase. In order to measure the rate of progesterone produced by the coupled enzymes, we have modified a radiochemical method which involves precipitation of pregnenolone by digitonin. Digitonin precipitation proved to be effective in separating unconverted pregnenolone from the steroid products of both enzyme reactions, progesterone and pregn-5-ene-3,20-dione. Neither the steroidal inhibitors nor the kinetic isotope effect altered the accuracy of the method for routine measurement of the overall rate of conversion of delta5,3beta-hydroxysteroid to delta4,3-ketosteroid.", "contents": "Human placental 3beta-hydroxysteroid dehydrogenase: delta5-isomerase. Demonstration of an intermediate in the conversion of 3beta-hydroxypregn-5-en-20-one to pregn-4-ene-3,20-dione. 3beta-Hydroxypregn-5-en-20-one (pregnenolone) and NAD+ were incubated with a solubilized preparation of the coupled enzyme 3beta-hydroxysteroid:NAD(P) oxidoreductase-3-ketosteroid delta4,delta5-isomerase (3beta-hydroxysteroid dehydrogenase: delta5-isomerase) from the mitochondrial fraction of human placenta. Unconverted pregnenolone, pregn-4-ene-3,20-dione (rogesterone), and a small but detectable amount of pregn-5-ene-3,20-dione were isolated from the medium by Sephadex LH-20 chromomatography. The identification of pregn-5-ene-3,20-dione, confirmed by mass fragmentography, has provided the first direct evidence for the formation of the hypothetical delta5,3-ketone intermediate in the conversion of pregnenolone to progesterone. When tritium-labeled pregnenolone and [4-14C]pregnenolone were incubated simultaneously the 3H:14C ratio in isolated pregn-5-ene-3,20-dione was 4.6 times greater than in isolated progesterone and pregnenolone, indicating a kinetic isotope effect in the enzymatic isomerization of tritium-labeled pregn-5-ene-3,20-dione. Exposure of the enzyme to two steroids which inhibit the overall enzyme reaction, 2alpha-cyano-17beta-hydroxy-4,4,17alpha-trimethylandrost-5-en-3-one (cyanoketone) and 3-hydroxyestra-1,3,5(10),6,8-pentaen-17-one (equilenin), increased the relative yield of labeled pregn-5-ene-3,20-dione as well as the recovery of radioactivity remaining as unconverted pregnenolone, suggesting that both the dehydrogenase and isomerase activities were inhibited. Exposure of the enzyme to equilenin increased the ratio of isolated pregn-5-ene-3,20-dione radioactivity to progesterone radioactivity as progesterone synthesis was inhibited. Equilenin also diminished the tritium isotope effect on the isomerase reaction. Both findings suggest that it is possible to inhibit the isomerase to a greater extent than the dehydrogenase. In order to measure the rate of progesterone produced by the coupled enzymes, we have modified a radiochemical method which involves precipitation of pregnenolone by digitonin. Digitonin precipitation proved to be effective in separating unconverted pregnenolone from the steroid products of both enzyme reactions, progesterone and pregn-5-ene-3,20-dione. Neither the steroidal inhibitors nor the kinetic isotope effect altered the accuracy of the method for routine measurement of the overall rate of conversion of delta5,3beta-hydroxysteroid to delta4,3-ketosteroid."} {"id": "PMID:1254589", "title": "In vivo metabolism of 4'-deoxypyridoxine in rat and man.", "content": "In rats 80 to 95% of 4'-deoxypyridoxine administered intraperitoneally, intravenously, intramuscularly, or subcutaneously was excreted in the urine within 7.5 hours. Orally administered deoxypyridoxine was also rapidly eliminated. Over one-half of the excreted material appeared as deoxypyridoxine-3-(hydrogen sulfate) and the remainder as unchanged deoxypyridoxine. Tissue concentrations of deoxypyridoxine 5'phosphate were comparable to those of pyridoxal 5'phosphate. In normal men about 50% of a single oral dose (3 to 7.5 mg/kg of body weight) appeared in the urine within 6 hours. 4'Deoxy-5-pyridoxic acid accounted for 50 to 100% of the excreted material. The remainder was unchanged deoxypyridoxine. No deoxypyridoxine-3-(hydrogen sulfate) was detected in human urine and no 4'-deoxy-5-pyridoxic acid was found in rat urine. Deoxypyridoxine 5'-phosphate was not detected in the urine of either species. The complexity of deoxypyridoxine metabolism indicated by these data suggests the use of caution in extrapolating data obtained with deoxypyridoxine to B6 metabolism in the absence of deoxypyridoxine, and particularly in extrapolating results from the rat to man. Synthesis for 4'-deoxypyridoxine-3-(ethyl carbonate), 4'-deoxypyridoxine 5'-acetate, 4'-deoxy-3-0-(2-sulfoethyl)-pyridoxine, and the metabolites are presented. These synthesis were facilitated by using ethylchloroformate conjugates and N-methylpiperazine hydrolysis to block and unblock the phenol group.", "contents": "In vivo metabolism of 4'-deoxypyridoxine in rat and man. In rats 80 to 95% of 4'-deoxypyridoxine administered intraperitoneally, intravenously, intramuscularly, or subcutaneously was excreted in the urine within 7.5 hours. Orally administered deoxypyridoxine was also rapidly eliminated. Over one-half of the excreted material appeared as deoxypyridoxine-3-(hydrogen sulfate) and the remainder as unchanged deoxypyridoxine. Tissue concentrations of deoxypyridoxine 5'phosphate were comparable to those of pyridoxal 5'phosphate. In normal men about 50% of a single oral dose (3 to 7.5 mg/kg of body weight) appeared in the urine within 6 hours. 4'Deoxy-5-pyridoxic acid accounted for 50 to 100% of the excreted material. The remainder was unchanged deoxypyridoxine. No deoxypyridoxine-3-(hydrogen sulfate) was detected in human urine and no 4'-deoxy-5-pyridoxic acid was found in rat urine. Deoxypyridoxine 5'-phosphate was not detected in the urine of either species. The complexity of deoxypyridoxine metabolism indicated by these data suggests the use of caution in extrapolating data obtained with deoxypyridoxine to B6 metabolism in the absence of deoxypyridoxine, and particularly in extrapolating results from the rat to man. Synthesis for 4'-deoxypyridoxine-3-(ethyl carbonate), 4'-deoxypyridoxine 5'-acetate, 4'-deoxy-3-0-(2-sulfoethyl)-pyridoxine, and the metabolites are presented. These synthesis were facilitated by using ethylchloroformate conjugates and N-methylpiperazine hydrolysis to block and unblock the phenol group."} {"id": "PMID:1254590", "title": "Conformation, enzymic activity, and immunochemistry of a lysozyme derivative modified at tryptophan 123 by reaction with 2,3-dioxo-5-indolinesulfonic acid.", "content": "Reaction of hen egg-white lysozyme with 2,3-dioxo-5-indolinesulfonic acid (DISA) yielded a homogeneous derivative which was modified at a single tryptophan residue. The modification was located at Trp-123. The absorption spectrum of the derivative showed a new peak in the visible range with lambdamax at 365 nm. In addition, the absorption maximum in the ultraviolet which appears in lysozyme at 280 nm was shifted to 270 nm in the derivative and appreciably enhanced. In ORD measurements, the rotatory behaviors of lysozyme and its derivative were identical at the 233 nm negative minimum and the 199 nm positive extremum. CD measurements gave equal [theta] values for lysozyme and derivative at the two negative ellipticity bands at 208 and 220 nm. Although no conformational differences between lysozyme and derivative were observed by ORD and CD measurements, some changes were detectable by chemical methods. Accessibility to tryptic hydrolysis and susceptibility of the disulfide bonds to reduction were increased in the derivative relative to lysozyme. The lytic activity of the derivative, which retained the same pH optimum as native lysozyme, was greatly (50%) decreased, probably as a result of the slight conformational change. With several antisera to lysozyme, the native protein and its derivative had equal antigenic reactivities. The findings were instrumental in further delineation of an antigenic reactive site in lysozyme.", "contents": "Conformation, enzymic activity, and immunochemistry of a lysozyme derivative modified at tryptophan 123 by reaction with 2,3-dioxo-5-indolinesulfonic acid. Reaction of hen egg-white lysozyme with 2,3-dioxo-5-indolinesulfonic acid (DISA) yielded a homogeneous derivative which was modified at a single tryptophan residue. The modification was located at Trp-123. The absorption spectrum of the derivative showed a new peak in the visible range with lambdamax at 365 nm. In addition, the absorption maximum in the ultraviolet which appears in lysozyme at 280 nm was shifted to 270 nm in the derivative and appreciably enhanced. In ORD measurements, the rotatory behaviors of lysozyme and its derivative were identical at the 233 nm negative minimum and the 199 nm positive extremum. CD measurements gave equal [theta] values for lysozyme and derivative at the two negative ellipticity bands at 208 and 220 nm. Although no conformational differences between lysozyme and derivative were observed by ORD and CD measurements, some changes were detectable by chemical methods. Accessibility to tryptic hydrolysis and susceptibility of the disulfide bonds to reduction were increased in the derivative relative to lysozyme. The lytic activity of the derivative, which retained the same pH optimum as native lysozyme, was greatly (50%) decreased, probably as a result of the slight conformational change. With several antisera to lysozyme, the native protein and its derivative had equal antigenic reactivities. The findings were instrumental in further delineation of an antigenic reactive site in lysozyme."} {"id": "PMID:1254591", "title": "The thrombin-like enzyme from Bothrops atrox snake venom. Properties of the enzyme purified by affinity chromatography on p-aminobenzamidine-substituted agarose.", "content": "The trhombin-like activities from the snake venoms of two subspecies of Bothrops atrox, moojeni (type I) and marajoensis (type II), were purified to homogeneity by affinity chromatography on a support consisting of the inhibitor, p-aminobenzamidine, linked to Sepharose 4B with a spacer of diaminodipropylaminosuccinate. At room temperature the enzyme was not bound to the affinity support but rather was retarded in relation to the unbound protein. As a result the thrombin-like activity eluted in a large volume following the main protein fraction. However, at 4 degrees the enzyme was absorbed to the affinity support and could be eluted specifically with the ligand benzamidine (0.15 M). Optimal conditions for column loading and washing were 0.05 M Tris.HCl/0.4 M NaCl, pH 9.0 at 4 degrees. The type I enzyme isolated in this manner showed a single major band on pH 8.9 disc gel electrophoresis as well as two minor bands. Further purification by isoelectric focusing yielded one major and two minor components. All three protein fractions had identical thrombin-like activities and amino acid composition. The major band had a specific activity of 210 to 230 NIH thrombin units/mg, a S20, w of 2.65 S, a molecular weight of 29,000, and an E1% 280 of 15.6. This protein has a carbohydrate content, measured as hexose, glucosamine, and sialic acid, of 27%. From the amino acid and carbohydrate composition a partial specific volume of 0.700 ml/g was calculated. The type I enzyme, purified on affinity chromatography only, did not activate Factor XIII and was free of thromboplastin-like activity. The type II enzyme behaved very differently from the type I on pH 8.9 polyacrylamide disc gels yielding two major bands and two minor bands. The relative amounts of these four bands were not a function of purity. The type II enzyme had a specific activity of 650 to 700 NIH thrombin units/mg, a S20, w of 2.60, and a molecular weight of 31,400.", "contents": "The thrombin-like enzyme from Bothrops atrox snake venom. Properties of the enzyme purified by affinity chromatography on p-aminobenzamidine-substituted agarose. The trhombin-like activities from the snake venoms of two subspecies of Bothrops atrox, moojeni (type I) and marajoensis (type II), were purified to homogeneity by affinity chromatography on a support consisting of the inhibitor, p-aminobenzamidine, linked to Sepharose 4B with a spacer of diaminodipropylaminosuccinate. At room temperature the enzyme was not bound to the affinity support but rather was retarded in relation to the unbound protein. As a result the thrombin-like activity eluted in a large volume following the main protein fraction. However, at 4 degrees the enzyme was absorbed to the affinity support and could be eluted specifically with the ligand benzamidine (0.15 M). Optimal conditions for column loading and washing were 0.05 M Tris.HCl/0.4 M NaCl, pH 9.0 at 4 degrees. The type I enzyme isolated in this manner showed a single major band on pH 8.9 disc gel electrophoresis as well as two minor bands. Further purification by isoelectric focusing yielded one major and two minor components. All three protein fractions had identical thrombin-like activities and amino acid composition. The major band had a specific activity of 210 to 230 NIH thrombin units/mg, a S20, w of 2.65 S, a molecular weight of 29,000, and an E1% 280 of 15.6. This protein has a carbohydrate content, measured as hexose, glucosamine, and sialic acid, of 27%. From the amino acid and carbohydrate composition a partial specific volume of 0.700 ml/g was calculated. The type I enzyme, purified on affinity chromatography only, did not activate Factor XIII and was free of thromboplastin-like activity. The type II enzyme behaved very differently from the type I on pH 8.9 polyacrylamide disc gels yielding two major bands and two minor bands. The relative amounts of these four bands were not a function of purity. The type II enzyme had a specific activity of 650 to 700 NIH thrombin units/mg, a S20, w of 2.60, and a molecular weight of 31,400."} {"id": "PMID:1254592", "title": "Allosteric transitions in cobalt hemoglobins.", "content": "Circular dichroism and difference ultraviolet visible spectra were obtained for cobalt hemoglobin derivatives. At 287 nm the ellipticity difference between the oxy- and deoxycobaltohemoglobin is about one-half as great as that for the native proteins indicating smaller quaternary conformational changes for the former. Deoxygenation increases the Soret rotational strengths of both iron and cobalt hemoglobins to comparable degrees suggesting similar conformational changes for their aromatic residues near the \"heme.\" Deoxygenation causes a much larger decrease of L band ellipticity for iron than cobalt hemoglobin. Circular dichroism spectra of nitrosylcobaltohemoglobin indicate the molecule to have a T quaternary structure. The circular dichroism spectra of cobaltihemoglobin do not seem to fit the patterns of the other cobalt derivatives and its 287 nm ellipticity is pH-dependent. From the shape of the Soret circular dichroism spectra, it is estimated that the transition dipole makes an angle with the line joining the two opposing pyrrole nitrogens of about 60 degrees for oxy- and deoxycobaltohemoglobin, 80 degrees for cobaltihemoglobin, as compared to 70 degrees for the native oxy- and deoxyhemoglobins. Inositol hexaphosphate has little or no effect on the circular dichroism spectra of cobalt hemoglobins in the 287 nm region, but it significantly increases the Soret rotational strength and decreases the L band ellipticity. The results are interpreted to mean that polyphosphates modify primarily the protein structure of hemoglobins at the tertiary level, and that the intersubunit interactions are weak in cobalt hemoglobins.", "contents": "Allosteric transitions in cobalt hemoglobins. Circular dichroism and difference ultraviolet visible spectra were obtained for cobalt hemoglobin derivatives. At 287 nm the ellipticity difference between the oxy- and deoxycobaltohemoglobin is about one-half as great as that for the native proteins indicating smaller quaternary conformational changes for the former. Deoxygenation increases the Soret rotational strengths of both iron and cobalt hemoglobins to comparable degrees suggesting similar conformational changes for their aromatic residues near the \"heme.\" Deoxygenation causes a much larger decrease of L band ellipticity for iron than cobalt hemoglobin. Circular dichroism spectra of nitrosylcobaltohemoglobin indicate the molecule to have a T quaternary structure. The circular dichroism spectra of cobaltihemoglobin do not seem to fit the patterns of the other cobalt derivatives and its 287 nm ellipticity is pH-dependent. From the shape of the Soret circular dichroism spectra, it is estimated that the transition dipole makes an angle with the line joining the two opposing pyrrole nitrogens of about 60 degrees for oxy- and deoxycobaltohemoglobin, 80 degrees for cobaltihemoglobin, as compared to 70 degrees for the native oxy- and deoxyhemoglobins. Inositol hexaphosphate has little or no effect on the circular dichroism spectra of cobalt hemoglobins in the 287 nm region, but it significantly increases the Soret rotational strength and decreases the L band ellipticity. The results are interpreted to mean that polyphosphates modify primarily the protein structure of hemoglobins at the tertiary level, and that the intersubunit interactions are weak in cobalt hemoglobins."} {"id": "PMID:1254593", "title": "Derivatives of Clostridium acidi-urici ferredoxin containing altered amino acid sequences. Semisynthetic synthesis, biological activity, and stability.", "content": "The semisynthetic syntheses and some properties of derivatives of Clostridium acidi-urici ferredoxin that contain amino acid deletions or replacements in the peptide chain are described. All 16 stable derivatives prepared, with the exception of [Trp2]ferredoxin, were fully active as electron carriers in the two enzymatic assay systems tested: the phosphoroclastic system and the ferrodoxin-dependent reduction of cytochrome c. E1Trp1]Ferredoxin had 70% of the activity of native ferredoxin in both assay systems. The stability in aerobic solution of [Ala1]ferredoxin, which had had its natural alanyl NH2-terminal residue removed and then replaced chemically, is the same as that of the native ferrodoxin (half-life of approximately 54 days). The relative stabilities of derivatives with a replacement or deletion of the NH2-terminal residue are as follows: [Ala1]- greater than or equal to [Phe1]-, [Lys1]-, [ Pro1]-, [Leu1]- greater than [Met1]- greater than [Gly1]- greater than [Glu1]- greater than des-Ala1-ferrodoxin. The data indicate that a large bulky residue, but not a negatively charged residue, is tolerated in position 1 of the peptide chain and the greatly decreased stability (half-life = 1 day) of des-Ala1-ferredoxin confirms the importance of the NH2-terminal residue for the stability of the protein. The relative stabilities of derivatives containing Ala1, but including a replacement for the normal Tyr2, are as follows: Native greater than [Trp2]- greater than or equal to [Phe2]- greater than [His2]- greater than [Leu2]- greater than [Pro2]ferredoxin. [Gly2]- and des-Ala1-Tyr2-apoferredoxin did not form stable derivatives upon reconstitution with iron and sulfide, nor did [3-NO2-Tyr2, 30]- and [Leu2,3-NO2-Tyr30]apoferredoxins. Other relatively stable and fully active derivatives prepared included: [3-NH2-Tyr30]-, [3-F-Phe2]-, and [2-F-Phe2]ferredoxin. The behavior of these various derivatives demonstrates the importance of the peptide chain for the stability of C. acidi-urici ferredoxin and shows that the activity of ferredoxin can be altered by a single amino acid substitution in the peptide chain.", "contents": "Derivatives of Clostridium acidi-urici ferredoxin containing altered amino acid sequences. Semisynthetic synthesis, biological activity, and stability. The semisynthetic syntheses and some properties of derivatives of Clostridium acidi-urici ferredoxin that contain amino acid deletions or replacements in the peptide chain are described. All 16 stable derivatives prepared, with the exception of [Trp2]ferredoxin, were fully active as electron carriers in the two enzymatic assay systems tested: the phosphoroclastic system and the ferrodoxin-dependent reduction of cytochrome c. E1Trp1]Ferredoxin had 70% of the activity of native ferredoxin in both assay systems. The stability in aerobic solution of [Ala1]ferredoxin, which had had its natural alanyl NH2-terminal residue removed and then replaced chemically, is the same as that of the native ferrodoxin (half-life of approximately 54 days). The relative stabilities of derivatives with a replacement or deletion of the NH2-terminal residue are as follows: [Ala1]- greater than or equal to [Phe1]-, [Lys1]-, [ Pro1]-, [Leu1]- greater than [Met1]- greater than [Gly1]- greater than [Glu1]- greater than des-Ala1-ferrodoxin. The data indicate that a large bulky residue, but not a negatively charged residue, is tolerated in position 1 of the peptide chain and the greatly decreased stability (half-life = 1 day) of des-Ala1-ferredoxin confirms the importance of the NH2-terminal residue for the stability of the protein. The relative stabilities of derivatives containing Ala1, but including a replacement for the normal Tyr2, are as follows: Native greater than [Trp2]- greater than or equal to [Phe2]- greater than [His2]- greater than [Leu2]- greater than [Pro2]ferredoxin. [Gly2]- and des-Ala1-Tyr2-apoferredoxin did not form stable derivatives upon reconstitution with iron and sulfide, nor did [3-NO2-Tyr2, 30]- and [Leu2,3-NO2-Tyr30]apoferredoxins. Other relatively stable and fully active derivatives prepared included: [3-NH2-Tyr30]-, [3-F-Phe2]-, and [2-F-Phe2]ferredoxin. The behavior of these various derivatives demonstrates the importance of the peptide chain for the stability of C. acidi-urici ferredoxin and shows that the activity of ferredoxin can be altered by a single amino acid substitution in the peptide chain."} {"id": "PMID:1254594", "title": "Mechanism and specificity of succinyl-CoA:3-ketoacid coenzyme A transferase.", "content": "(a) The reactivity of substituted acetates as substrates for CoA transferase increases sharply with increasing basicity and exhibits a slope of 1.0 in a plot of either log kappacat or log (kappacat/Km) against pKa (betanuc = 1.0). This result shows that the catalyzed reaction, which involves both carboxylate activation and leaving group transfer, does not proceed through a fully concerted reaction mechanism in the rate-determining step. The result is consistent with a stepwise reaction mechanism that proceeds through an anhydride intermediate. (b) Equilibrium constants for thiol ester formation, either bound to the enzyme or free in solution, show the same dependence on the basicity of carboxylate ions (betaeq = 1.0) and are independent of acidity when expressed in terms of the carboxylic acid. Thus, the polar environment around substituents on the acyl group is the same for carboxylic acids, thiol esters, and oxygen esters. (c) The interaction of the terminal CH3CO group of acetoacetate with the active site causes a 200,000-fold increase in kappacat/Km, corresponding to a decrease in delta G++ OF 7.2 kcal/mol compared with an unsubstituted acid of the same pK. The binding energy of the coenzyme A moiety of the substrate is utilized to interact with the active site and cause a 10(4) to 10(6)-fold increase in kappacat, corresponding to a decrease in delta G++ of 6 to 9 kcal/mol, compared with fragments of the coenzyme A moiety added separatly or together. (d) The exchange of labeled coenzyme A into acyl-CoA substrates was found to be greater than or equal to 10(5) slower than substrate turnover.", "contents": "Mechanism and specificity of succinyl-CoA:3-ketoacid coenzyme A transferase. (a) The reactivity of substituted acetates as substrates for CoA transferase increases sharply with increasing basicity and exhibits a slope of 1.0 in a plot of either log kappacat or log (kappacat/Km) against pKa (betanuc = 1.0). This result shows that the catalyzed reaction, which involves both carboxylate activation and leaving group transfer, does not proceed through a fully concerted reaction mechanism in the rate-determining step. The result is consistent with a stepwise reaction mechanism that proceeds through an anhydride intermediate. (b) Equilibrium constants for thiol ester formation, either bound to the enzyme or free in solution, show the same dependence on the basicity of carboxylate ions (betaeq = 1.0) and are independent of acidity when expressed in terms of the carboxylic acid. Thus, the polar environment around substituents on the acyl group is the same for carboxylic acids, thiol esters, and oxygen esters. (c) The interaction of the terminal CH3CO group of acetoacetate with the active site causes a 200,000-fold increase in kappacat/Km, corresponding to a decrease in delta G++ OF 7.2 kcal/mol compared with an unsubstituted acid of the same pK. The binding energy of the coenzyme A moiety of the substrate is utilized to interact with the active site and cause a 10(4) to 10(6)-fold increase in kappacat, corresponding to a decrease in delta G++ of 6 to 9 kcal/mol, compared with fragments of the coenzyme A moiety added separatly or together. (d) The exchange of labeled coenzyme A into acyl-CoA substrates was found to be greater than or equal to 10(5) slower than substrate turnover."} {"id": "PMID:1254595", "title": "Utilization of the inactivation rate of coenzyme A transferase by thiol reagents to determine properties of the enzyme-CoA intermediate.", "content": "The rate of inactivation of succinyl-CoA:3-ketoacid coenzyme A transferase by thiol reagents is increased 3 to 100 times by very low concentrations of acyl-CoA substrates. The same maximum inactivation rate is found with acetoacetyl-CoA and succinyl-CoA. The enhanced rate of inactivation is caused by the stoichiometric formation of the enzyme-CoA intermediate and an accompanying conformation change of the enzyme. The inactivation rate provides a simple assay for the amount of enzyme present as the enzyme-CoA intermediate, using only catalytic concentrations of enzyme. This technique has been utilized to measure (a) a rate constant for hydrolysis of the enzyme-CoA intermediate of 0.10 min-1 at pH 8.1; (b) a stoichiometry of two active sites per enzyme molecule; and (c) the equilibrium constants for formation of the enzyme-CoA intermediate from dilute solutions of substrates (and hence for the overall reaction) by determining the ratio of [enzyme-CoA]/[enzyme] in the presence of a series of substrate \"buffers\" at different ratios of [RCOO-]/[RCOSCoA]. As the total concentration of acyl-CoA and carbosylate substrates is increased, the inactivation rate is decreased. This indicates that the Michaelis complexes are protected against inactivation.", "contents": "Utilization of the inactivation rate of coenzyme A transferase by thiol reagents to determine properties of the enzyme-CoA intermediate. The rate of inactivation of succinyl-CoA:3-ketoacid coenzyme A transferase by thiol reagents is increased 3 to 100 times by very low concentrations of acyl-CoA substrates. The same maximum inactivation rate is found with acetoacetyl-CoA and succinyl-CoA. The enhanced rate of inactivation is caused by the stoichiometric formation of the enzyme-CoA intermediate and an accompanying conformation change of the enzyme. The inactivation rate provides a simple assay for the amount of enzyme present as the enzyme-CoA intermediate, using only catalytic concentrations of enzyme. This technique has been utilized to measure (a) a rate constant for hydrolysis of the enzyme-CoA intermediate of 0.10 min-1 at pH 8.1; (b) a stoichiometry of two active sites per enzyme molecule; and (c) the equilibrium constants for formation of the enzyme-CoA intermediate from dilute solutions of substrates (and hence for the overall reaction) by determining the ratio of [enzyme-CoA]/[enzyme] in the presence of a series of substrate \"buffers\" at different ratios of [RCOO-]/[RCOSCoA]. As the total concentration of acyl-CoA and carbosylate substrates is increased, the inactivation rate is decreased. This indicates that the Michaelis complexes are protected against inactivation."} {"id": "PMID:1254596", "title": "Properties of biologically active messenger RNA from human placenta. Cell-free synthesis of two immunoreactive forms of placental lactogen.", "content": "In order to understand better the regulation of human placental proteins the activity of placental lactogen messenger RNA has been examined. Total RNA was extracted from normal term placentas and purified by chromatography on oligo(dT)-cellulose. The poly(A)-containing fraction stimulated amino acid incorporation 5- to 10-fold in wheat germ cell-free extracts, and immunoprecipitation of the translation products with antiserum directed against human placental lactogen (hPL) suggests that about 2% of the peptides contain hPL determinants. Analysis of the material precipitated with hPL antiserum by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels revealed two major species, one co-migrating with hPL and the other migrating slightly slower than hPL. On DEAE-cellulose chromatography the former material eluted close to authentic hPL while the latter material eluted at higher ionic strength than hPL, indicating a difference in net charge of these two species. Tryptic peptide analysis of the large material and authentic hPL shows marked similarities in the primary structure of these two proteins. The slower migrating peptide has an apparent molecular weight about 3000 larger than hPL and thus may represent a precursor molecule. Both cell-free products could be competed out of immunoprecipitates by a large excess of authentic hPL, confirming their immunologic similarities. Centrifugation of the placental poly(A)-containing RNA through aqueous glycerol gradients indicates that the hPL mRNA sediments at about 14 S.", "contents": "Properties of biologically active messenger RNA from human placenta. Cell-free synthesis of two immunoreactive forms of placental lactogen. In order to understand better the regulation of human placental proteins the activity of placental lactogen messenger RNA has been examined. Total RNA was extracted from normal term placentas and purified by chromatography on oligo(dT)-cellulose. The poly(A)-containing fraction stimulated amino acid incorporation 5- to 10-fold in wheat germ cell-free extracts, and immunoprecipitation of the translation products with antiserum directed against human placental lactogen (hPL) suggests that about 2% of the peptides contain hPL determinants. Analysis of the material precipitated with hPL antiserum by electrophoresis on sodium dodecyl sulfate-polyacrylamide gels revealed two major species, one co-migrating with hPL and the other migrating slightly slower than hPL. On DEAE-cellulose chromatography the former material eluted close to authentic hPL while the latter material eluted at higher ionic strength than hPL, indicating a difference in net charge of these two species. Tryptic peptide analysis of the large material and authentic hPL shows marked similarities in the primary structure of these two proteins. The slower migrating peptide has an apparent molecular weight about 3000 larger than hPL and thus may represent a precursor molecule. Both cell-free products could be competed out of immunoprecipitates by a large excess of authentic hPL, confirming their immunologic similarities. Centrifugation of the placental poly(A)-containing RNA through aqueous glycerol gradients indicates that the hPL mRNA sediments at about 14 S."} {"id": "PMID:1254597", "title": "Group fractionation of eukaryotic ribosomal proteins.", "content": "The proteins of the subunits of rat liver ribosomes were fractionated by stepwise elution from carboxymethylcellulose with LiCl at pH 6.5. The 40 S ribosomal proteins were separated into five groups containing between 3 and 14 proteins; the 60 S proteins, into seven groups of 3 to 15. Only a comparatively small number of proteins occurred in appreciable amounts in more than one group. The number of relatively acidic proteins associated with the ribosomal subunits was larger than had been reported before: it is not known if they are initiation or translation factors or ribosomal structural proteins. The group fractionation procedure has proven valuable as the initial step in the isolation and characterization of rat liver ribosomal proteins.", "contents": "Group fractionation of eukaryotic ribosomal proteins. The proteins of the subunits of rat liver ribosomes were fractionated by stepwise elution from carboxymethylcellulose with LiCl at pH 6.5. The 40 S ribosomal proteins were separated into five groups containing between 3 and 14 proteins; the 60 S proteins, into seven groups of 3 to 15. Only a comparatively small number of proteins occurred in appreciable amounts in more than one group. The number of relatively acidic proteins associated with the ribosomal subunits was larger than had been reported before: it is not known if they are initiation or translation factors or ribosomal structural proteins. The group fractionation procedure has proven valuable as the initial step in the isolation and characterization of rat liver ribosomal proteins."} {"id": "PMID:1254598", "title": "Induction of multiple forms of mouse liver cytochrome P-450. Evidence for genetically controlled de novo protein synthesis in response to treatment with beta-naphthoflavone or phenobarbital.", "content": "The administration of polycyclic aromatic compounds such as beta-naphthoflavone or 3-methylcholanthrene is known to cause the induction of many liver microsomal monoxygenase activities and the appearance of a distinct cytochrome called P-448 in genetically responsive, but not in nonresponsive, inbred mouse strains. However, the administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin induces these activities and cytochrome P-448 formation to the same extent in both responsive and nonresponsive inbred strains. In contrast, phenobarbital or pregnenolone-16 alpha-carbonitrile induces in both responsive and nonresponsive strains a different profile of enzyme activities and the appearance of cytochrome P-450 (rather than cytochrome P-448). In the present studies, electrophoresis of liver microsomal proteins from inbred C57BL/6N and DBA/2N and recombinant inbred AKXL-38 and AKXL-38A mouse strains revealed the presence of four polypeptides whose relative staining intensity could be correlated with the induction state of the microsomes as determined by enzymatic and spectral methods. Of these four bands, Band 4 (55,000 daltons) was increased whenever spectral measurements revealed an increase in the cytochrome P-448 content due to administration of beta-naphthoflavone or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Administration of pregnenolone-16alpha-carbonitrile caused an increase in Band 3 (54,000 daltons), whereas administration of phenobarbital caused an increase primarily in Band 2 (51,000 daltons) but also smaller increases in Band 1 (49,000 daltons) and Band 4. The changes observed for phenobarbital and pregnenolone-16alpha-carbonitrile were the same for both responsive and nonresponsive strains. The same electrophoretic technique was used to measure the incorporation of radioactive leucine into microsomal proteins. Microsomes were prepared from liver combined from responsive mice (C57BL/6N) treated with beta-naphthoflavone and L-[14C]leucine and nonresponsive mice (DBA/2N) treated with beta-naphthoflavone and L-[3H-4,5]leucine. A significant increase in the 14C/3H ratio was observed for Band 4, and decreases were seen for Bands 1 and 2. In similar experiments with other mice and phenobarbital as the inducing agent with L-[14C]leucine and the vehicle alone with L-[3H-4,5]leucine, the 14C/3H ratio was markedly increased for Band 2, and smaller increases were observed for Bands 1 and 4. These results and other data presented indicate that the increased formation of cytochrome P-448 and P-450 by beta-naphthoflavone and phenobarbital, respectively, is primarily the result of an increased rate of de novo protein synthesis rather than a decreased degradation rate or a conversion of pre-existing polypeptides.", "contents": "Induction of multiple forms of mouse liver cytochrome P-450. Evidence for genetically controlled de novo protein synthesis in response to treatment with beta-naphthoflavone or phenobarbital. The administration of polycyclic aromatic compounds such as beta-naphthoflavone or 3-methylcholanthrene is known to cause the induction of many liver microsomal monoxygenase activities and the appearance of a distinct cytochrome called P-448 in genetically responsive, but not in nonresponsive, inbred mouse strains. However, the administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin induces these activities and cytochrome P-448 formation to the same extent in both responsive and nonresponsive inbred strains. In contrast, phenobarbital or pregnenolone-16 alpha-carbonitrile induces in both responsive and nonresponsive strains a different profile of enzyme activities and the appearance of cytochrome P-450 (rather than cytochrome P-448). In the present studies, electrophoresis of liver microsomal proteins from inbred C57BL/6N and DBA/2N and recombinant inbred AKXL-38 and AKXL-38A mouse strains revealed the presence of four polypeptides whose relative staining intensity could be correlated with the induction state of the microsomes as determined by enzymatic and spectral methods. Of these four bands, Band 4 (55,000 daltons) was increased whenever spectral measurements revealed an increase in the cytochrome P-448 content due to administration of beta-naphthoflavone or 2,3,7,8-tetrachlorodibenzo-p-dioxin. Administration of pregnenolone-16alpha-carbonitrile caused an increase in Band 3 (54,000 daltons), whereas administration of phenobarbital caused an increase primarily in Band 2 (51,000 daltons) but also smaller increases in Band 1 (49,000 daltons) and Band 4. The changes observed for phenobarbital and pregnenolone-16alpha-carbonitrile were the same for both responsive and nonresponsive strains. The same electrophoretic technique was used to measure the incorporation of radioactive leucine into microsomal proteins. Microsomes were prepared from liver combined from responsive mice (C57BL/6N) treated with beta-naphthoflavone and L-[14C]leucine and nonresponsive mice (DBA/2N) treated with beta-naphthoflavone and L-[3H-4,5]leucine. A significant increase in the 14C/3H ratio was observed for Band 4, and decreases were seen for Bands 1 and 2. In similar experiments with other mice and phenobarbital as the inducing agent with L-[14C]leucine and the vehicle alone with L-[3H-4,5]leucine, the 14C/3H ratio was markedly increased for Band 2, and smaller increases were observed for Bands 1 and 4. These results and other data presented indicate that the increased formation of cytochrome P-448 and P-450 by beta-naphthoflavone and phenobarbital, respectively, is primarily the result of an increased rate of de novo protein synthesis rather than a decreased degradation rate or a conversion of pre-existing polypeptides."} {"id": "PMID:1254599", "title": "Purification and properties of a new polypeptide chain elongation factor, EF-1beta, from pig liver.", "content": "Eukaryotic polypeptide elongation factor 1 (EF-1) from pig liver has been resolved into two complementary factors, EF-1alpha and EF-1beta (Iwasaki, K., Mizumoto, K., Tanka, M., and Kaziro, Y. (1973) J. Biochem. (Tokyo) 74, 849). This paper describes the procedures for purification of EF-1beta and some properties of the purified factor. The purification method includes an aqueous two-phase separation technique, a treatment of the crude factor with sodium cholate and two successive column chromatographies on diethyl-aminoethyl-Sephadex A-50. By this method, EF-1beta was purified about 50-fold starting from the material obtained after two-phase separation followed by ammonium sulfate fractionation with a recovery of 20%. The purified EF-1beta appeared homogeneous, having a molecular weight of about 90,000. It consisted of two unequal subunits of the molecular weights of 55,000 and 30,000. It stimulates polymerization of phenylalanine dependent on poly(U) in the presence of both EF-1alpha and EF-2, as well as the EF-1alpha-dependent binding of phenylalanyl-tRNA to ribosomes in the presence of GTP. However, it had no effect on the stoichiometric binding of phenylalanyl-tRNA to ribosomes dependent on EF-1alpha in the presence of guanyl-5'-yl methylenediphosphonate. These results indicate that the function of EF-1beta is to stimulate the recycling of EF-1alpha.", "contents": "Purification and properties of a new polypeptide chain elongation factor, EF-1beta, from pig liver. Eukaryotic polypeptide elongation factor 1 (EF-1) from pig liver has been resolved into two complementary factors, EF-1alpha and EF-1beta (Iwasaki, K., Mizumoto, K., Tanka, M., and Kaziro, Y. (1973) J. Biochem. (Tokyo) 74, 849). This paper describes the procedures for purification of EF-1beta and some properties of the purified factor. The purification method includes an aqueous two-phase separation technique, a treatment of the crude factor with sodium cholate and two successive column chromatographies on diethyl-aminoethyl-Sephadex A-50. By this method, EF-1beta was purified about 50-fold starting from the material obtained after two-phase separation followed by ammonium sulfate fractionation with a recovery of 20%. The purified EF-1beta appeared homogeneous, having a molecular weight of about 90,000. It consisted of two unequal subunits of the molecular weights of 55,000 and 30,000. It stimulates polymerization of phenylalanine dependent on poly(U) in the presence of both EF-1alpha and EF-2, as well as the EF-1alpha-dependent binding of phenylalanyl-tRNA to ribosomes in the presence of GTP. However, it had no effect on the stoichiometric binding of phenylalanyl-tRNA to ribosomes dependent on EF-1alpha in the presence of guanyl-5'-yl methylenediphosphonate. These results indicate that the function of EF-1beta is to stimulate the recycling of EF-1alpha."} {"id": "PMID:1254612", "title": "The influence of surface chemistry on implant interface histology: a theoretical basis for implant materials selection.", "content": "A theory is proposed stating that an ideal implant material must have a dynamic surface chemistry that induces histological changes at the implant interface which would normally occur if the implant were not present. Evidence for the validity of this theory is provided with a series of bone-implant studies which result in stable interfacial osteogenesis under specific implant surface chemistry conditions. Insufficient or excess surface ion concentrations produce negative osteogenesis and fixation results. Implantation of osteogenic implants in soft tissues also produces undesirable histological responses as proposed in the theory. A variety of surface chemical analyses of the implant are reviewed which provide a scientific basis for the implant surface theory.", "contents": "The influence of surface chemistry on implant interface histology: a theoretical basis for implant materials selection. A theory is proposed stating that an ideal implant material must have a dynamic surface chemistry that induces histological changes at the implant interface which would normally occur if the implant were not present. Evidence for the validity of this theory is provided with a series of bone-implant studies which result in stable interfacial osteogenesis under specific implant surface chemistry conditions. Insufficient or excess surface ion concentrations produce negative osteogenesis and fixation results. Implantation of osteogenic implants in soft tissues also produces undesirable histological responses as proposed in the theory. A variety of surface chemical analyses of the implant are reviewed which provide a scientific basis for the implant surface theory."} {"id": "PMID:1254613", "title": "Biocompatibility of materials for total joint replacement.", "content": "The clinical use of total joint prostheses demands absolute biocompatibility of the materials employed. The purpose of this experiment was the bioassay of some materials considered as possible candidates for use in total joint prostheses as load-bearing members or as wear-resistant surfaces. Some materials already in use were also tested. 316L stainless steel was used as a control. The materials were implanted as a standardized rod and in particulate form. An average of 12 samples per material were implanted in soft tissue for six months and a total of 145 rabbits were used in this study. Twenty-five materials including metals, polymers, and ceramics were tested in solid and powdered form. A semiquantitative evaluation of local tissue reaction and a study of organs was performed. Polymers and metallic materials showed in general a mild tissue reaction. Ceramics, which some authors describe as the best tolerated materials, elicited variable tissue responses. Some of these (glass-ceramics) presented very poor tissue tolerance. The least reactive, titanium oxide, titanium aluminate, and aluminum oxide, presented a degree of tissue reaction comparable to that of corrosion resistant metals, but not superior to them. Moderate reactivity was the general rule for particulate materials except for the Pyroceram glass-ceramics, polymides, and Teflon. Ultrahigh molecular weight polyethylene in particulate form elicited a rather cellular tissue response, a fact to be considered when projecting long-term results in total joint arthroplasty. No pathological changes compatible with systemic toxicity by materials tested were observed in the study of the organs.", "contents": "Biocompatibility of materials for total joint replacement. The clinical use of total joint prostheses demands absolute biocompatibility of the materials employed. The purpose of this experiment was the bioassay of some materials considered as possible candidates for use in total joint prostheses as load-bearing members or as wear-resistant surfaces. Some materials already in use were also tested. 316L stainless steel was used as a control. The materials were implanted as a standardized rod and in particulate form. An average of 12 samples per material were implanted in soft tissue for six months and a total of 145 rabbits were used in this study. Twenty-five materials including metals, polymers, and ceramics were tested in solid and powdered form. A semiquantitative evaluation of local tissue reaction and a study of organs was performed. Polymers and metallic materials showed in general a mild tissue reaction. Ceramics, which some authors describe as the best tolerated materials, elicited variable tissue responses. Some of these (glass-ceramics) presented very poor tissue tolerance. The least reactive, titanium oxide, titanium aluminate, and aluminum oxide, presented a degree of tissue reaction comparable to that of corrosion resistant metals, but not superior to them. Moderate reactivity was the general rule for particulate materials except for the Pyroceram glass-ceramics, polymides, and Teflon. Ultrahigh molecular weight polyethylene in particulate form elicited a rather cellular tissue response, a fact to be considered when projecting long-term results in total joint arthroplasty. No pathological changes compatible with systemic toxicity by materials tested were observed in the study of the organs."} {"id": "PMID:1254614", "title": "Electrical stimulation of bone growth into porous A12O3.", "content": "Porous, cylindrical, high alumina, ceramic structures were fabricated for implantation in the superior third of canine femoral medullary canals. Implant durations of one, two, four, and eight weeks using three animals per time period were studied. A constant current (10 muA) power supply was used to attempt to stimulate bone growth into the porous ceramic structures. Osseous tissue in-growth was evaluated using a mechanical push-out test, microadiography, and histological thin sectioning. The interfacial shear strength and tissue micro-structure was studied as a function of implant residence site and implant residence site and implant residence time. The results indicate that initially the proximal implants have a higher interfacial shear strength, however, after eight weeks of implantation the distal implants have a shear strength about twice that of the proximal implants. This trend is observed for both the electrically stimulated and nonstimulated specimens. The 10 muA current level used in this investigation was found to have a small but significant effect on shear strength increasing it at implantation times of less than eight weeks.", "contents": "Electrical stimulation of bone growth into porous A12O3. Porous, cylindrical, high alumina, ceramic structures were fabricated for implantation in the superior third of canine femoral medullary canals. Implant durations of one, two, four, and eight weeks using three animals per time period were studied. A constant current (10 muA) power supply was used to attempt to stimulate bone growth into the porous ceramic structures. Osseous tissue in-growth was evaluated using a mechanical push-out test, microadiography, and histological thin sectioning. The interfacial shear strength and tissue micro-structure was studied as a function of implant residence site and implant residence site and implant residence time. The results indicate that initially the proximal implants have a higher interfacial shear strength, however, after eight weeks of implantation the distal implants have a shear strength about twice that of the proximal implants. This trend is observed for both the electrically stimulated and nonstimulated specimens. The 10 muA current level used in this investigation was found to have a small but significant effect on shear strength increasing it at implantation times of less than eight weeks."} {"id": "PMID:1254615", "title": "An in vitro study of bacterial response to inert and reactive metals and to methyl methacrylate.", "content": "The clinical use of inert materials for internal fixation and joint replacement devices is increasing rapidly; studies on the effect of these materials on bacteria and host resistance to infection have not kept apace. Any substance placed within the body may interfere with host-parasite interaction, either by its physical presence or by physiochemical activity at its interface with the surrounding tissue. Either mechanism, by altering the normal host defense mechanism, may promote or retard bacterial growth. Bacterial growth may also be altered if a trace element essential to or inhibitory to the bacteria or an element that antagonizes or potentiates humoral antibacterial systems is leached from the substance. We have tested bacterial growth and inhibition in vitro in the presence of substances used as implant materials: surgical silver, iron, zinc-coated galvanized iron, aluminum alloy, stainless steel, Vitallium, and methyl methacrylate. Our results showed: 1) metals that have low grades of tissue reactivity and little bacteriotoxic effect provided a framework along which bacterial growth and propagation occurred; 2) metals that have higher levels of cellular reactivity, specifically aluminum and galvanized wire, caused selective bacterial toxicity. The in vitro response of bacteria to methyl methacrylate was similar to that of Vitallium and other inert substances, i.e., growth and propagation were abundant adjacent to methyl methacrylate. These studies led us to speculate that, if similar phenomena occur in vivo, bacterial growth and dissemination might be increased when an inert implant material was used and decreased when the implant material was more reactive.", "contents": "An in vitro study of bacterial response to inert and reactive metals and to methyl methacrylate. The clinical use of inert materials for internal fixation and joint replacement devices is increasing rapidly; studies on the effect of these materials on bacteria and host resistance to infection have not kept apace. Any substance placed within the body may interfere with host-parasite interaction, either by its physical presence or by physiochemical activity at its interface with the surrounding tissue. Either mechanism, by altering the normal host defense mechanism, may promote or retard bacterial growth. Bacterial growth may also be altered if a trace element essential to or inhibitory to the bacteria or an element that antagonizes or potentiates humoral antibacterial systems is leached from the substance. We have tested bacterial growth and inhibition in vitro in the presence of substances used as implant materials: surgical silver, iron, zinc-coated galvanized iron, aluminum alloy, stainless steel, Vitallium, and methyl methacrylate. Our results showed: 1) metals that have low grades of tissue reactivity and little bacteriotoxic effect provided a framework along which bacterial growth and propagation occurred; 2) metals that have higher levels of cellular reactivity, specifically aluminum and galvanized wire, caused selective bacterial toxicity. The in vitro response of bacteria to methyl methacrylate was similar to that of Vitallium and other inert substances, i.e., growth and propagation were abundant adjacent to methyl methacrylate. These studies led us to speculate that, if similar phenomena occur in vivo, bacterial growth and dissemination might be increased when an inert implant material was used and decreased when the implant material was more reactive."} {"id": "PMID:1254616", "title": "Hyaluronidase-bound membrane as a biomaterial for implantable fuel cells.", "content": "A new biomaterial containing covalently bound hyaluronidase was prepared. An application of this enzyme membrane is to improve the performance of an implantable fuel cell. Hyaluronic acid is a contributor to the viscosity of tissue fluids but can be a potential fuel source because of its sugar content. The incorporation of immobilized hyaluronidase would not only contribute to a more available fuel supply by splitting hyaluronic acid but, perhaps more importantly, enhance the rate of mass transport of fuel, O2, and reaction products by reducing the viscosity near the electrode membranes. Hyaluronidase was bound to Sepharose gel and its thermoplastic membrane after activation by cyanogen bromide. Fourteen and 22% of the activities were recovered from the gel and membrane, respectively. The activity of the bound enzyme was stable for six months at 0 degrees C. The addition of hyaluronic acid, 1 mg/ml, to a typical implantable type bioautofuel cell in vitro increased external solution viscosity from 1.1 to 2.5-2.8 cP and reduced voltage output under 10 komega by 60% in 3 hr. When the hyaluronidase bound membrane was placed at the anode, viscosity of the glucose-hyaluronic acid solution was lowered to 1.8 cP and the cell output increased to the original level of a glucose-fueled cell in 3 hr. Glucosamine-equivalent released from hyaluronic acid at the electrode was 3.1 mg after 22.5 hr. This represents 90% of the theoretical consumption. Restoration of the cell output was probably a combination of the enhanced transport of fuel, O2 and products, and/or appearance of a new fuel, glucosamine-equivalent.", "contents": "Hyaluronidase-bound membrane as a biomaterial for implantable fuel cells. A new biomaterial containing covalently bound hyaluronidase was prepared. An application of this enzyme membrane is to improve the performance of an implantable fuel cell. Hyaluronic acid is a contributor to the viscosity of tissue fluids but can be a potential fuel source because of its sugar content. The incorporation of immobilized hyaluronidase would not only contribute to a more available fuel supply by splitting hyaluronic acid but, perhaps more importantly, enhance the rate of mass transport of fuel, O2, and reaction products by reducing the viscosity near the electrode membranes. Hyaluronidase was bound to Sepharose gel and its thermoplastic membrane after activation by cyanogen bromide. Fourteen and 22% of the activities were recovered from the gel and membrane, respectively. The activity of the bound enzyme was stable for six months at 0 degrees C. The addition of hyaluronic acid, 1 mg/ml, to a typical implantable type bioautofuel cell in vitro increased external solution viscosity from 1.1 to 2.5-2.8 cP and reduced voltage output under 10 komega by 60% in 3 hr. When the hyaluronidase bound membrane was placed at the anode, viscosity of the glucose-hyaluronic acid solution was lowered to 1.8 cP and the cell output increased to the original level of a glucose-fueled cell in 3 hr. Glucosamine-equivalent released from hyaluronic acid at the electrode was 3.1 mg after 22.5 hr. This represents 90% of the theoretical consumption. Restoration of the cell output was probably a combination of the enhanced transport of fuel, O2 and products, and/or appearance of a new fuel, glucosamine-equivalent."} {"id": "PMID:1254617", "title": "The rate of bone ingrowth into porous metal.", "content": "Experiments have been devised to study the rate of ingrowth of bone into porous metal with pore sizes up to 100 mu and to study the significance of a gap between the porous metal surface and bone. When the porous coat was in direct apposition with bone, the implant was firmly locked in place after a three week period and the plateau value of implant-tissue shear strength was reached at four weeks. A gap of 1.5 mm between the bone and the implant was bridged by new bone within four weeks.", "contents": "The rate of bone ingrowth into porous metal. Experiments have been devised to study the rate of ingrowth of bone into porous metal with pore sizes up to 100 mu and to study the significance of a gap between the porous metal surface and bone. When the porous coat was in direct apposition with bone, the implant was firmly locked in place after a three week period and the plateau value of implant-tissue shear strength was reached at four weeks. A gap of 1.5 mm between the bone and the implant was bridged by new bone within four weeks."} {"id": "PMID:1254618", "title": "An evaluation of bone growth into porous high density polyethylene.", "content": "The purpose of this investigation was to study bone growth into porous polyethylene rods as a function of time and pore structure. Previous studies have indicated the biocompatibility of solid polyethylene materials which are currently being used clinically. Porous polyethylene rods were implanted in the femurs of mongrel dogs which are sacrificed four, eight, and 16 weeks postoperatively. The implants were then sectioned and examined histologically and microadiographically. Quantitative techniques were employed to determine the amount of bone ingrowth as a function of time and pore size. The pore structures of the materials were evaluated using optical microscopy and mercury intrusion porosimetry. The results of this investigation have demonstrated that porous polyethylene is capable of accepting bone growth into pores as small as 40 mum. The optimum rate of bone ingrowth was observed in pore sizes of approximately 100 to 135 mum, with no increase in the rate of bone ingrowth observed in samples possessing larger pore sizes. No adverse tissue response was found at implant times up to 16 weeks in pore sizes of 100 mum or larger.", "contents": "An evaluation of bone growth into porous high density polyethylene. The purpose of this investigation was to study bone growth into porous polyethylene rods as a function of time and pore structure. Previous studies have indicated the biocompatibility of solid polyethylene materials which are currently being used clinically. Porous polyethylene rods were implanted in the femurs of mongrel dogs which are sacrificed four, eight, and 16 weeks postoperatively. The implants were then sectioned and examined histologically and microadiographically. Quantitative techniques were employed to determine the amount of bone ingrowth as a function of time and pore size. The pore structures of the materials were evaluated using optical microscopy and mercury intrusion porosimetry. The results of this investigation have demonstrated that porous polyethylene is capable of accepting bone growth into pores as small as 40 mum. The optimum rate of bone ingrowth was observed in pore sizes of approximately 100 to 135 mum, with no increase in the rate of bone ingrowth observed in samples possessing larger pore sizes. No adverse tissue response was found at implant times up to 16 weeks in pore sizes of 100 mum or larger."} {"id": "PMID:1254619", "title": "Classification of knee ligament instabilities. Part I. The medial compartment and cruciate ligaments.", "content": "Based on the clinical and operative findings in sixty-eight knees with acute tears of the medial compartment and cruciate ligaments, a standardized terminology and classification of knee ligament instability is presented. With an intact posterior cruciate ligament, anteromedial, anterolateral, or posterolateral rotatory instability may occur, but not true posteromedial rotatory instability. With the posterior cruciate ligament ruptured, straight anterior, posterior, medial, or lateral instability may be found.", "contents": "Classification of knee ligament instabilities. Part I. The medial compartment and cruciate ligaments. Based on the clinical and operative findings in sixty-eight knees with acute tears of the medial compartment and cruciate ligaments, a standardized terminology and classification of knee ligament instability is presented. With an intact posterior cruciate ligament, anteromedial, anterolateral, or posterolateral rotatory instability may occur, but not true posteromedial rotatory instability. With the posterior cruciate ligament ruptured, straight anterior, posterior, medial, or lateral instability may be found."} {"id": "PMID:1254620", "title": "Classification of knee ligament instabilities. Part II. The lateral compartment.", "content": "Lateral instability of the knee is less frequent but more disabling than medial instability of a comparable amount. At the same time the diagnostic tests for lateral instability are more subtle and more frequently misinterpreted. Posterolateral rotatory subluxation is demonstrated by an apparently positive posterior drawer test with the tibia in neutral rotation or by the external rotation-recurvatum test with the knee in extension. Anterolateral rotatory subluxation is present when the anterior drawer test with the tibia in neutral rotation demonstrates that the lateral tibial condyle appears to become more prominent or that both condyles appear to become equally prominent.", "contents": "Classification of knee ligament instabilities. Part II. The lateral compartment. Lateral instability of the knee is less frequent but more disabling than medial instability of a comparable amount. At the same time the diagnostic tests for lateral instability are more subtle and more frequently misinterpreted. Posterolateral rotatory subluxation is demonstrated by an apparently positive posterior drawer test with the tibia in neutral rotation or by the external rotation-recurvatum test with the knee in extension. Anterolateral rotatory subluxation is present when the anterior drawer test with the tibia in neutral rotation demonstrates that the lateral tibial condyle appears to become more prominent or that both condyles appear to become equally prominent."} {"id": "PMID:1254621", "title": "The anterior cruciate ligament. A functional analysis based on postmortem studies.", "content": "In forty fresh human cadaver knees the function of the anterior cruciate ligament and of its two component parts, the posterolateral part and the anteromedial band, were studied by cutting these ligaments and others in different sequences and combinations and then manually stressing the knees. The anterior drawer sign cannot be obtained unless the anteromedial band is severed. The postolateral part and the medial collateral ligament are, respectively, the secondary and tertiary restraints limiting the anterior drawer sign. Both internal and external rotation are limited by the anterior cruciate ligament, especially when the knee is in extension. The anterior cruciate ligament also limits hyperextension.", "contents": "The anterior cruciate ligament. A functional analysis based on postmortem studies. In forty fresh human cadaver knees the function of the anterior cruciate ligament and of its two component parts, the posterolateral part and the anteromedial band, were studied by cutting these ligaments and others in different sequences and combinations and then manually stressing the knees. The anterior drawer sign cannot be obtained unless the anteromedial band is severed. The postolateral part and the medial collateral ligament are, respectively, the secondary and tertiary restraints limiting the anterior drawer sign. Both internal and external rotation are limited by the anterior cruciate ligament, especially when the knee is in extension. The anterior cruciate ligament also limits hyperextension."} {"id": "PMID:1254622", "title": "Experimental stabilization of segmental defects in the human femur. A torsional study.", "content": "One of each of thirty-five pairs of fresh intact femora were tested to failure in torsion, recording the dynamic torque, the absorbed energy, and the angle of rotation. These results were compared with the results obtained with the contralateral femur, reconstituted after removal of a segment. Intramedullary nails with polymethylmethacrylate cement, strips of titanium mesh with cement, bone plates with and without cement, and multiple Steinmann pins with cement were the reconstituting configurations. Bone plates were the strongest configuration; the failure torques in all cases were limited by the stress concentration effects of the holes in the bone used for screw fixation. The use of cement as an adjunct to single-plate fixation provided some additional strength. The torsional strength of femora fixed with K\u00fcntscher and Schneider nails was limited by failure of the cement and bone. The use of titanium mesh with polymethylmethacrylate was less effective, because this composite has a low torsional rigidity. The use of multiple Steinmann pins packed with polymethylmethacrylate in the medullary cavity should be discouraged because severe twisting and fragmentation of the surrounding acrylic will occur at low levels of torque.", "contents": "Experimental stabilization of segmental defects in the human femur. A torsional study. One of each of thirty-five pairs of fresh intact femora were tested to failure in torsion, recording the dynamic torque, the absorbed energy, and the angle of rotation. These results were compared with the results obtained with the contralateral femur, reconstituted after removal of a segment. Intramedullary nails with polymethylmethacrylate cement, strips of titanium mesh with cement, bone plates with and without cement, and multiple Steinmann pins with cement were the reconstituting configurations. Bone plates were the strongest configuration; the failure torques in all cases were limited by the stress concentration effects of the holes in the bone used for screw fixation. The use of cement as an adjunct to single-plate fixation provided some additional strength. The torsional strength of femora fixed with K\u00fcntscher and Schneider nails was limited by failure of the cement and bone. The use of titanium mesh with polymethylmethacrylate was less effective, because this composite has a low torsional rigidity. The use of multiple Steinmann pins packed with polymethylmethacrylate in the medullary cavity should be discouraged because severe twisting and fragmentation of the surrounding acrylic will occur at low levels of torque."} {"id": "PMID:1254623", "title": "A comparison of cortical bone atrophy secondary to fixation with plates with large differences in bending stiffness.", "content": "Two internal-fixation plates with large differences in bending stiffness were applied to pairs of intact femora of six adult mongrel dogs to study the osteoporosis induced by rigid fixation. After nine and twelve months of plate application a significant, increased amount of bone atrophy was seen on the rigidly plated side. Biomechanical measurements of specimens from various segments of both femoral diaphyses showed the bones to have similar mechanical properties (as tissue), but different structural properties (as organ). These findings suggest that the osteoporosis due to rigid plate fixation occurs by thinning of the cortex rather than by reduction of the mechanical properties of the osseous tissue.", "contents": "A comparison of cortical bone atrophy secondary to fixation with plates with large differences in bending stiffness. Two internal-fixation plates with large differences in bending stiffness were applied to pairs of intact femora of six adult mongrel dogs to study the osteoporosis induced by rigid fixation. After nine and twelve months of plate application a significant, increased amount of bone atrophy was seen on the rigidly plated side. Biomechanical measurements of specimens from various segments of both femoral diaphyses showed the bones to have similar mechanical properties (as tissue), but different structural properties (as organ). These findings suggest that the osteoporosis due to rigid plate fixation occurs by thinning of the cortex rather than by reduction of the mechanical properties of the osseous tissue."} {"id": "PMID:1254624", "title": "Normal and abnormal motion of the shoulder.", "content": "The roentgenographic parameters of motion in normal and abnormal shoulders, including the movement of the scapula, arm angle, glenohumeral angle, scapulothoracic angle, excursion of the humeral head, and instant center of motion for abduction in the plane of the scapula, were determined in twelve normal subjects and fifteen patients. The scapula rotated externally with abduction. The ratio of glenohumeral to scapulothoracic movement was 5:4 after about 30 degrees of abduction. The center of rotation of the glenohumeral joint for abduction in the plane of the scapula was located within six millimeters of the geometric center of the humeral ball. The average excursion of the humeral ball on the face of the glenoid in the superoinferior plane between each 30-degree arc of motion was less than 1.5 millimeters in normal subjects. Significant previous injury resulting in abnormal mechanics of the shoulder joint was associated with abnormal values for excursion of the instant center and of the humeral head. An abnormal glenohumeral-to-scapulothoracic ratio was associated with significant pain in the shoulder. The fact that these various parameters were sensitive indicators of normal and abnormal motion raises the possibility of diagnostic clinical application.", "contents": "Normal and abnormal motion of the shoulder. The roentgenographic parameters of motion in normal and abnormal shoulders, including the movement of the scapula, arm angle, glenohumeral angle, scapulothoracic angle, excursion of the humeral head, and instant center of motion for abduction in the plane of the scapula, were determined in twelve normal subjects and fifteen patients. The scapula rotated externally with abduction. The ratio of glenohumeral to scapulothoracic movement was 5:4 after about 30 degrees of abduction. The center of rotation of the glenohumeral joint for abduction in the plane of the scapula was located within six millimeters of the geometric center of the humeral ball. The average excursion of the humeral ball on the face of the glenoid in the superoinferior plane between each 30-degree arc of motion was less than 1.5 millimeters in normal subjects. Significant previous injury resulting in abnormal mechanics of the shoulder joint was associated with abnormal values for excursion of the instant center and of the humeral head. An abnormal glenohumeral-to-scapulothoracic ratio was associated with significant pain in the shoulder. The fact that these various parameters were sensitive indicators of normal and abnormal motion raises the possibility of diagnostic clinical application."} {"id": "PMID:1254625", "title": "Electromyography before and after surgery for hip deformity in children with cerebral palsy. A comparison of clinical and electromyographic findings.", "content": "Twenty-three ambulatory children with spastic diplegic cerebral palsy were evaluated clinically and by electromyography before and after hip-muscle surgery. The stretch tests originally designed to distinguish specific muscle tightness and spasticity were found to be non-specific when tested by electromyography. Ambulatory electromyograms using needle electrodes and telemetry generally showed decreased activity in the released muscles and, on occasion, changes in activity in muscles not operated on. These unanticipated changes after release may explain some of the unpredictability of results of such procedures in cerebral palsy.", "contents": "Electromyography before and after surgery for hip deformity in children with cerebral palsy. A comparison of clinical and electromyographic findings. Twenty-three ambulatory children with spastic diplegic cerebral palsy were evaluated clinically and by electromyography before and after hip-muscle surgery. The stretch tests originally designed to distinguish specific muscle tightness and spasticity were found to be non-specific when tested by electromyography. Ambulatory electromyograms using needle electrodes and telemetry generally showed decreased activity in the released muscles and, on occasion, changes in activity in muscles not operated on. These unanticipated changes after release may explain some of the unpredictability of results of such procedures in cerebral palsy."} {"id": "PMID:1254626", "title": "Femoral trabecular-pattern index and bone mineral content measurement by photon absorption in senile osteoporosis.", "content": "A comparative study of the usefulness of the femoral trabecular-pattern index (Singh index) and bone mineral content measurement by photon absorption in senile osteoporosis was performed in 106 white women, seventy to ninety-five years old. In 17% of the subjects adequate hip roentgenograms could not be obtained. Interpretation of the Singh index was not found to be simple and easily reproducible. A positive correlation was noted between the bone mineral content and the Singh index. The incidence of previous vertebral and non-vertebral fracture was noted to be inversely related to both bone mineral content and the Singh index, but neither method clearly separated subjects with fracture from those without fracture.", "contents": "Femoral trabecular-pattern index and bone mineral content measurement by photon absorption in senile osteoporosis. A comparative study of the usefulness of the femoral trabecular-pattern index (Singh index) and bone mineral content measurement by photon absorption in senile osteoporosis was performed in 106 white women, seventy to ninety-five years old. In 17% of the subjects adequate hip roentgenograms could not be obtained. Interpretation of the Singh index was not found to be simple and easily reproducible. A positive correlation was noted between the bone mineral content and the Singh index. The incidence of previous vertebral and non-vertebral fracture was noted to be inversely related to both bone mineral content and the Singh index, but neither method clearly separated subjects with fracture from those without fracture."} {"id": "PMID:1254627", "title": "The fate of hypertrophic chondrocytes of the epiphyseal plate. An electron microscopic study.", "content": "An ultrastructural study of the distal femoral epiphyseal-metaphyseal junction of C3H mice revealed that the hypertrophic chondrocytes undergo degenerative changes leading to their death. While most chondrocytes will die before their lacunae are opened to the marrow, others survive for a time in lacunae which communicate with the primary spongiosa, but they also ultimately die. There was no evidence to indicate that hypertrophic chondrocytes survive or are transformed into other cells.", "contents": "The fate of hypertrophic chondrocytes of the epiphyseal plate. An electron microscopic study. An ultrastructural study of the distal femoral epiphyseal-metaphyseal junction of C3H mice revealed that the hypertrophic chondrocytes undergo degenerative changes leading to their death. While most chondrocytes will die before their lacunae are opened to the marrow, others survive for a time in lacunae which communicate with the primary spongiosa, but they also ultimately die. There was no evidence to indicate that hypertrophic chondrocytes survive or are transformed into other cells."} {"id": "PMID:1254628", "title": "Total hip replacement in patients with ankylosing spondylitis with involvement of the hip.", "content": "Twenty-three patients with ankylosing spondylitis underwent thirty-four total hip arthroplasties with an average follow-up of 42.5 months. The over-all results were rated good in all but two patients. Significant benefit was obtained in posture and function so that these patients could be gainfully employed. Improvement in the sum total range of motion was 96.1 degrees in patients with bone ankylosis and 150 degrees in those with fibrous ankylosis. The preoperative sum total range of motion was maintained or improved in hips with a painful arc of motion. Most of the limited motion in patients with ankylosed hips was due to myositis ossificans.", "contents": "Total hip replacement in patients with ankylosing spondylitis with involvement of the hip. Twenty-three patients with ankylosing spondylitis underwent thirty-four total hip arthroplasties with an average follow-up of 42.5 months. The over-all results were rated good in all but two patients. Significant benefit was obtained in posture and function so that these patients could be gainfully employed. Improvement in the sum total range of motion was 96.1 degrees in patients with bone ankylosis and 150 degrees in those with fibrous ankylosis. The preoperative sum total range of motion was maintained or improved in hips with a painful arc of motion. Most of the limited motion in patients with ankylosed hips was due to myositis ossificans."} {"id": "PMID:1254629", "title": "Tibial lengthening using a new extension device. Report of thirty-two cases.", "content": "Using a new type of external fixation device for lengthening the tibia, lengthenings of from 3.5 to 6.5 centimeters were accomplished in thirty-two children, eight to seventeen years old, the six complications, none of which jeopardized the result. The procedure was painless and the patients were ambulatory on crutches two to three days after operation, while lengthening was continued as an out-patient procedure.", "contents": "Tibial lengthening using a new extension device. Report of thirty-two cases. Using a new type of external fixation device for lengthening the tibia, lengthenings of from 3.5 to 6.5 centimeters were accomplished in thirty-two children, eight to seventeen years old, the six complications, none of which jeopardized the result. The procedure was painless and the patients were ambulatory on crutches two to three days after operation, while lengthening was continued as an out-patient procedure."} {"id": "PMID:1254630", "title": "Batchelor's extra-articular subtalar arthrodesis. A report on sixty-four procedures in patients with poliomyelitic deformities.", "content": "Sixty-four feet of fifty-four patients treated with Batchelor's extra-articular subtalar arthrodesis for poliomyelitic deformities were reviewed after a minimum follow-up of four years. Early in the series the results were poor because of inexperience with the technique and poor selection of patients. The incidence of non-union, which appeared to be high in this series compared with other series in which the Grice technique was used, was attributed mainly to the more advanced age of our patients at the time of arthrodesis (average age, 9.9 years). A common factor in the cause of non-union was tightness of the heel cord. Redistribution of muscles to balance power in the foot did not appear to be necessary to achieve good results in feet with equinovalgus deformity, and conversely, energetic redistribution of muscle power in these feet did not result in late varus deformity.", "contents": "Batchelor's extra-articular subtalar arthrodesis. A report on sixty-four procedures in patients with poliomyelitic deformities. Sixty-four feet of fifty-four patients treated with Batchelor's extra-articular subtalar arthrodesis for poliomyelitic deformities were reviewed after a minimum follow-up of four years. Early in the series the results were poor because of inexperience with the technique and poor selection of patients. The incidence of non-union, which appeared to be high in this series compared with other series in which the Grice technique was used, was attributed mainly to the more advanced age of our patients at the time of arthrodesis (average age, 9.9 years). A common factor in the cause of non-union was tightness of the heel cord. Redistribution of muscles to balance power in the foot did not appear to be necessary to achieve good results in feet with equinovalgus deformity, and conversely, energetic redistribution of muscle power in these feet did not result in late varus deformity."} {"id": "PMID:1254631", "title": "Bucket-handle tear of the medial meniscus. A case for conservative surgery.", "content": "To compare the results of two methods of treatment for bucket-handle tears of the medial meniscus eighty-seven knees were studied, thirty-seven treated by excision of the bucket-handle tear alone and fifty by total meniscectomy. A postoperative history suggestive of locking was given by one patient in each treatment group. Anteroposterior laxity was found in 72% of knees treated by excision of the bucket-handle tear alone as compared with 68% of the knees treated by total meniscectomy, but in all other respects the results showed a marginal preference in favor of the simpler operation. Although the numbers are too small to prove that results are better following excision of the bucket-handle tear alone, it is suggested, in the absence of evidence that total meniscectomy is more advantageous, that the simpler operation of excision of just the bucket-handle tear is the treatment of choice in bucket-handle tears of the medial meniscus.", "contents": "Bucket-handle tear of the medial meniscus. A case for conservative surgery. To compare the results of two methods of treatment for bucket-handle tears of the medial meniscus eighty-seven knees were studied, thirty-seven treated by excision of the bucket-handle tear alone and fifty by total meniscectomy. A postoperative history suggestive of locking was given by one patient in each treatment group. Anteroposterior laxity was found in 72% of knees treated by excision of the bucket-handle tear alone as compared with 68% of the knees treated by total meniscectomy, but in all other respects the results showed a marginal preference in favor of the simpler operation. Although the numbers are too small to prove that results are better following excision of the bucket-handle tear alone, it is suggested, in the absence of evidence that total meniscectomy is more advantageous, that the simpler operation of excision of just the bucket-handle tear is the treatment of choice in bucket-handle tears of the medial meniscus."} {"id": "PMID:1254632", "title": "Recurrent anterior dislocation of the shoulder. Long-term follow-up of the Putti-Platt and Bankart procedures.", "content": "Follow-up of 176 patients among 223 who underwent 232 repairs for recurrent shoulder dislocation (average follow-up, 10.2 years) revealed a recurrence rate of 11%. Among the twenty with recurrence, important factors were youth, athletic activity, inadequate immobilization, a history of contralateral dislocation, and a family history of shoulder dislocation. Redislocation occurred two years or more after operation in seven of the twenty patients with recurrence. Surgical repair permitted good function without significant pain in most cases.", "contents": "Recurrent anterior dislocation of the shoulder. Long-term follow-up of the Putti-Platt and Bankart procedures. Follow-up of 176 patients among 223 who underwent 232 repairs for recurrent shoulder dislocation (average follow-up, 10.2 years) revealed a recurrence rate of 11%. Among the twenty with recurrence, important factors were youth, athletic activity, inadequate immobilization, a history of contralateral dislocation, and a family history of shoulder dislocation. Redislocation occurred two years or more after operation in seven of the twenty patients with recurrence. Surgical repair permitted good function without significant pain in most cases."} {"id": "PMID:1254633", "title": "The modified Bristow procedure for recurrent dislocation of the shoulder.", "content": "A review of fifty-one cases of the modified Bristow procedure for recurrent anterior shoulder instability is presented. The results were favorable. The redislocation rate was 2% with few complications. The average limitation of motion was 11 degrees of external rotation. Athletic individuals with involvement of the dominant shoulder were not capable of returning to high performance levels of overhead sports activity (particularly throwing) after the operation.", "contents": "The modified Bristow procedure for recurrent dislocation of the shoulder. A review of fifty-one cases of the modified Bristow procedure for recurrent anterior shoulder instability is presented. The results were favorable. The redislocation rate was 2% with few complications. The average limitation of motion was 11 degrees of external rotation. Athletic individuals with involvement of the dominant shoulder were not capable of returning to high performance levels of overhead sports activity (particularly throwing) after the operation."} {"id": "PMID:1254639", "title": "Genetic analysis of membrane differentiation in Paramecium. Freeze-fracture study of the trichocyst cycle in wild-type and mutant strains.", "content": "Using a series of mutants of Paramecium tetraurelia, we demonstrate, for the first time, changes in the internal structure of the cell membrane, as revealed by freeze-fracture, that correspond to specific single gene mutations. On the plasma membrane of Paramecium circular arrays of particles mark the sites of attachment of the tips of the intracellular secretory organelles-trichocysts. In wild-type paramecia, where attached trichocysts can be expelled by exocytosis under various stimuli, the plasma membrane array is composed of a double outer ring of particles (300 nm in diameter) and inside the ring a central rosette (fusion rosette) of particles (76 nm in diameter). Mutant nd9, characterized by a thermosensitive ability to discharge trichocysts, shows the same organization in cells grown at the permissive temperature (18 degrees C), while in cells grown at the nonpermissive temperature (27 degrees C) the rosette is missing. In mutant tam 8, characterized by normal but unattached trichocysts, and in mutant tl, completely devoid of trichocysts, no rosette is formed and the outer rings always show a modified configuration called \"parentheses\", also found in wild-type and in nd9 (18 degrees C) cells. From this comparison between wild type and mutants, we conclude: (a) that the formation of parentheses is a primary differentiation of the plasma membrane, independent of the presence of trichocysts, while the secondary transformation of parentheses into circular arrays and the formation of the rosette are triggered by interaction between trichocysts and plasma membranes; and (b) that the formation of the rosette is a prerequisite for trichocyst exocytosis.", "contents": "Genetic analysis of membrane differentiation in Paramecium. Freeze-fracture study of the trichocyst cycle in wild-type and mutant strains. Using a series of mutants of Paramecium tetraurelia, we demonstrate, for the first time, changes in the internal structure of the cell membrane, as revealed by freeze-fracture, that correspond to specific single gene mutations. On the plasma membrane of Paramecium circular arrays of particles mark the sites of attachment of the tips of the intracellular secretory organelles-trichocysts. In wild-type paramecia, where attached trichocysts can be expelled by exocytosis under various stimuli, the plasma membrane array is composed of a double outer ring of particles (300 nm in diameter) and inside the ring a central rosette (fusion rosette) of particles (76 nm in diameter). Mutant nd9, characterized by a thermosensitive ability to discharge trichocysts, shows the same organization in cells grown at the permissive temperature (18 degrees C), while in cells grown at the nonpermissive temperature (27 degrees C) the rosette is missing. In mutant tam 8, characterized by normal but unattached trichocysts, and in mutant tl, completely devoid of trichocysts, no rosette is formed and the outer rings always show a modified configuration called \"parentheses\", also found in wild-type and in nd9 (18 degrees C) cells. From this comparison between wild type and mutants, we conclude: (a) that the formation of parentheses is a primary differentiation of the plasma membrane, independent of the presence of trichocysts, while the secondary transformation of parentheses into circular arrays and the formation of the rosette are triggered by interaction between trichocysts and plasma membranes; and (b) that the formation of the rosette is a prerequisite for trichocyst exocytosis."} {"id": "PMID:1254640", "title": "Quantitation of junctional and extrajunctional acetylcholine receptors by electron microscope autoradiography after 125I-alpha-bungarotoxin binding at mouse neuromuscular junctions.", "content": "The distribution and quantitation of 125I-alpha-bungarotoxin (alpha-BTX) binding sites and thus acetylcholine receptor (AChR) were determined in mouse sternomastoid muscle by electron microscope autoradiography. We found that a valid criterion for receptor saturation at the neuromuscular junction was the complete elimination of neurally evoked tetanic muscle contractions, since, when such a criterion was used for the endpoint of toxin incubation, alpha-BTX was bound to approximately 90% of total available endplate sites. When, without implying localization, the presynaptic axonal membrane was used as a convenient reference structure, the concentration of alpha-BTX relative to this membrane was determined to be 46,000 +/- 27% sites/mum2.", "contents": "Quantitation of junctional and extrajunctional acetylcholine receptors by electron microscope autoradiography after 125I-alpha-bungarotoxin binding at mouse neuromuscular junctions. The distribution and quantitation of 125I-alpha-bungarotoxin (alpha-BTX) binding sites and thus acetylcholine receptor (AChR) were determined in mouse sternomastoid muscle by electron microscope autoradiography. We found that a valid criterion for receptor saturation at the neuromuscular junction was the complete elimination of neurally evoked tetanic muscle contractions, since, when such a criterion was used for the endpoint of toxin incubation, alpha-BTX was bound to approximately 90% of total available endplate sites. When, without implying localization, the presynaptic axonal membrane was used as a convenient reference structure, the concentration of alpha-BTX relative to this membrane was determined to be 46,000 +/- 27% sites/mum2."} {"id": "PMID:1254641", "title": "Involvement of vesicle coat material in casein secretion and surface regeneration.", "content": "The ultrastructure of the apical zone of lactating rat mammary epithelial cells was studied with emphasis on vesicle coat structures. Typical 40-60 nm ID \"coated vesicles\" were abundant, frequently associated with the internal filamentous plasma membrane coat or in direct continuity with secretory vesicles (SV) or plasma membrane proper. Bristle coats partially or totally covered membranes of secretory vesicles identified by their casein micelle content. This coat survived SV isolation. Exocytotic fusion of SV membranes and release of the casein micelles was observed. Frequently, regularly arranged bristle coat structures were identified in those regions of the plasma membrane that were involved in exocytotic processes. Both coated and uncoated surfaces of the casein-containing vesicles, as well as typical \"coated vesicles\", were frequently associated with microtubules and/or microfilaments. We suggest that coat materials of vesicles are related or identical to components of the internal coat of the surface membrane and that new plasma membrane and associated internal coat is produced concomitantly by fusion and integration of bristle coat moieties. Postexocytotic association of secreted casein micelles with the cell surface, mediated by finely filamentous extensions, provided a marker for the integrated vesicle membrane. An arrangement of SV with the inner surface of the plasma membrane is described which is characterized by regularly spaced, heabily stained membrane to membrane cross-bridges (pre-exocytotic attachment plaques). Such membrane-interconnecting elements may represent a form of coat structure important to recognition and interaction of membrane surfaces.", "contents": "Involvement of vesicle coat material in casein secretion and surface regeneration. The ultrastructure of the apical zone of lactating rat mammary epithelial cells was studied with emphasis on vesicle coat structures. Typical 40-60 nm ID \"coated vesicles\" were abundant, frequently associated with the internal filamentous plasma membrane coat or in direct continuity with secretory vesicles (SV) or plasma membrane proper. Bristle coats partially or totally covered membranes of secretory vesicles identified by their casein micelle content. This coat survived SV isolation. Exocytotic fusion of SV membranes and release of the casein micelles was observed. Frequently, regularly arranged bristle coat structures were identified in those regions of the plasma membrane that were involved in exocytotic processes. Both coated and uncoated surfaces of the casein-containing vesicles, as well as typical \"coated vesicles\", were frequently associated with microtubules and/or microfilaments. We suggest that coat materials of vesicles are related or identical to components of the internal coat of the surface membrane and that new plasma membrane and associated internal coat is produced concomitantly by fusion and integration of bristle coat moieties. Postexocytotic association of secreted casein micelles with the cell surface, mediated by finely filamentous extensions, provided a marker for the integrated vesicle membrane. An arrangement of SV with the inner surface of the plasma membrane is described which is characterized by regularly spaced, heabily stained membrane to membrane cross-bridges (pre-exocytotic attachment plaques). Such membrane-interconnecting elements may represent a form of coat structure important to recognition and interaction of membrane surfaces."} {"id": "PMID:1254642", "title": "Structural complexes in the squid giant axon membrane sensitive to ionic concentrations and cardiac glycosides.", "content": "Giant nerve fibers of squid Sepioteuthis sepioidea were incubated for 10 min in artificial sea water (ASW) under control conditions, in the absence of various ions, and in the presence of cardiac glycosides. The nerve fibers were fixed in OsO4 and embedded in Epon, and structural complexes along the axolemma were studied.", "contents": "Structural complexes in the squid giant axon membrane sensitive to ionic concentrations and cardiac glycosides. Giant nerve fibers of squid Sepioteuthis sepioidea were incubated for 10 min in artificial sea water (ASW) under control conditions, in the absence of various ions, and in the presence of cardiac glycosides. The nerve fibers were fixed in OsO4 and embedded in Epon, and structural complexes along the axolemma were studied."} {"id": "PMID:1254643", "title": "Platelet factors stimulate fibroblasts and smooth muscle cells quiescent in plasma serum to proliferate.", "content": "Whole blood serum is widely recognized as essential for the growth of diploid cells in culture. Dermal fibroblasts and arterial smooth muscle cells fail to proliferate in culture in the presence of serum derived from platelet-poor plasma. Platelet-poor plasma serum is capable of maintaining monkey arterial smooth muscle cells quiescent in culture at either low (1.5 x 10(3)) or high (2.0 x 10(4)) population densities. The proportion of cell traversing the cell cycle under these conditions was approximately 3%. Equal numbers of quiescent smooth muscle cells initiated DNA synthesis and cell division when treated with whole blood serum or with an equivalent quantity of platelet-poor plasma serum supplemented with a factor(s) derived from a supernate obtained after exposure of human platelets to purified thrombin in vitro.", "contents": "Platelet factors stimulate fibroblasts and smooth muscle cells quiescent in plasma serum to proliferate. Whole blood serum is widely recognized as essential for the growth of diploid cells in culture. Dermal fibroblasts and arterial smooth muscle cells fail to proliferate in culture in the presence of serum derived from platelet-poor plasma. Platelet-poor plasma serum is capable of maintaining monkey arterial smooth muscle cells quiescent in culture at either low (1.5 x 10(3)) or high (2.0 x 10(4)) population densities. The proportion of cell traversing the cell cycle under these conditions was approximately 3%. Equal numbers of quiescent smooth muscle cells initiated DNA synthesis and cell division when treated with whole blood serum or with an equivalent quantity of platelet-poor plasma serum supplemented with a factor(s) derived from a supernate obtained after exposure of human platelets to purified thrombin in vitro."} {"id": "PMID:1254644", "title": "Carbamycholine prevents giant granule-formation in cultured fibroblasts from beige (Chediak-Higashi) mice.", "content": "Primary embryonic fibroblasts isolated from beige (Chediak-Higashi) mice develop pathognomonic giant granules in vitro. Inclusion in the culture medium of carbamylcholine (carbachol) or phorbol myristate acetate (PMA) results in the generation of morphologically normally granules. Chediak-Higashi fibroblasts are highly susceptible to shape changes induced by colchicine. This abnormal property is also corrected by carbachol and PMA.", "contents": "Carbamycholine prevents giant granule-formation in cultured fibroblasts from beige (Chediak-Higashi) mice. Primary embryonic fibroblasts isolated from beige (Chediak-Higashi) mice develop pathognomonic giant granules in vitro. Inclusion in the culture medium of carbamylcholine (carbachol) or phorbol myristate acetate (PMA) results in the generation of morphologically normally granules. Chediak-Higashi fibroblasts are highly susceptible to shape changes induced by colchicine. This abnormal property is also corrected by carbachol and PMA."} {"id": "PMID:1254645", "title": "Intranuclear complexes in a copper-tolerant green alga.", "content": "The results of ultrastructural studies and transmission electron microscope microanalysis of two Scenedesmus strains experimentally exposed to copper sulfate are presented. A fine-structural examination of the cells revealed the presence of nuclear inclusions in the form of central dense-core complexes. Cytoplasmic structures resembling the intranuclear inclusions were occasionally found in the cells. TEM-X-ray microanalysis of these structures has provided evidence that the inclusions contain copper. It is concluded that their presence may be regarded as a detoxifying mechanism.", "contents": "Intranuclear complexes in a copper-tolerant green alga. The results of ultrastructural studies and transmission electron microscope microanalysis of two Scenedesmus strains experimentally exposed to copper sulfate are presented. A fine-structural examination of the cells revealed the presence of nuclear inclusions in the form of central dense-core complexes. Cytoplasmic structures resembling the intranuclear inclusions were occasionally found in the cells. TEM-X-ray microanalysis of these structures has provided evidence that the inclusions contain copper. It is concluded that their presence may be regarded as a detoxifying mechanism."} {"id": "PMID:1254646", "title": "Cautionary note on the use of [methyl-3H]thymidine to measure rates of chloroplast DNA synthesis in Chlamydomonas reinhardtii.", "content": "Commercial [methyl-3H]thymidine preparations tested here contain about a 0.2% contaminant which is rapidly incorporated into Chlamydomonas DNA. This contaminant obscures the measurement of the rate of chloroplast DNA synthesis when methyl-labeled preparations are used. Such contaminants are not present in ring-labeled (either 3H or 14C) thymidine preparations. In ring-labeled thymidine preparations, a slower incorporation rate commensurate with cell density is observed. These slower, long-term incorporation kinetics would be expected for the utilization of bona fide thymidine into chloroplast DNA.", "contents": "Cautionary note on the use of [methyl-3H]thymidine to measure rates of chloroplast DNA synthesis in Chlamydomonas reinhardtii. Commercial [methyl-3H]thymidine preparations tested here contain about a 0.2% contaminant which is rapidly incorporated into Chlamydomonas DNA. This contaminant obscures the measurement of the rate of chloroplast DNA synthesis when methyl-labeled preparations are used. Such contaminants are not present in ring-labeled (either 3H or 14C) thymidine preparations. In ring-labeled thymidine preparations, a slower incorporation rate commensurate with cell density is observed. These slower, long-term incorporation kinetics would be expected for the utilization of bona fide thymidine into chloroplast DNA."} {"id": "PMID:1254647", "title": "Oscillations of calcium ion concentrations in Physarum polycephalum.", "content": "Aequorin is a photoprotein which emits light in response to changes in free calcium concentration. When aequorin was microinjected into plasmodia of Physarum polycephalum, light emission varied in synchrony with the motile oscillations of the organisms. Therefore, movement is correlated which changes in the concentration of free calcium.", "contents": "Oscillations of calcium ion concentrations in Physarum polycephalum. Aequorin is a photoprotein which emits light in response to changes in free calcium concentration. When aequorin was microinjected into plasmodia of Physarum polycephalum, light emission varied in synchrony with the motile oscillations of the organisms. Therefore, movement is correlated which changes in the concentration of free calcium."} {"id": "PMID:1254648", "title": "Rhodopsin in the rod outer segment plasma membrane.", "content": "Isolated frog retinas were incubated in vitro with a 4-h pulse of [3H]leucine, then chased for 32 h with a nonradioactive amino acid mixture. At the end of the incubation, light and electron microscope autoradiograms were prepared from some of the retinas. The autoradiograms revealed: (a) intense radioactivity in the basal disks of the rod outer segments, (b) diffuse label evenly distributed throughout the rod outer segments, and (c) a high concentration of label in the entire rod outer segment plasma membrane. Incubation under identical conditions, but with puromycin added, significantly inhibited the labeling of all of these components. To identify the labeled proteins, purified outer segments from the remaining retinas were analyzed biochemically by SDS disc gel electrophoresis and gel filtration chromatography. SDS gel electrophoresis showed that about 90% of the total rod outer segment radioactivity chromatographed coincident with visual pigment, suggesting that the radiolabeled protein in the plasma membrane is visual pigment. Gel filtration chromatography demonstrated that the radiolabeled protein co-chromatographed with rhodopsin rather than opsin, and that the newly synthesized visual pigment is both the basal disks and the plasma membrane is present in the native configuration.", "contents": "Rhodopsin in the rod outer segment plasma membrane. Isolated frog retinas were incubated in vitro with a 4-h pulse of [3H]leucine, then chased for 32 h with a nonradioactive amino acid mixture. At the end of the incubation, light and electron microscope autoradiograms were prepared from some of the retinas. The autoradiograms revealed: (a) intense radioactivity in the basal disks of the rod outer segments, (b) diffuse label evenly distributed throughout the rod outer segments, and (c) a high concentration of label in the entire rod outer segment plasma membrane. Incubation under identical conditions, but with puromycin added, significantly inhibited the labeling of all of these components. To identify the labeled proteins, purified outer segments from the remaining retinas were analyzed biochemically by SDS disc gel electrophoresis and gel filtration chromatography. SDS gel electrophoresis showed that about 90% of the total rod outer segment radioactivity chromatographed coincident with visual pigment, suggesting that the radiolabeled protein in the plasma membrane is visual pigment. Gel filtration chromatography demonstrated that the radiolabeled protein co-chromatographed with rhodopsin rather than opsin, and that the newly synthesized visual pigment is both the basal disks and the plasma membrane is present in the native configuration."} {"id": "PMID:1254649", "title": "Relationship between chromosome condensation and metaphase lysine-rich histone phosphorylation.", "content": "Treatment of metaphase HTC cells with ZnCl2 inhibits histone phosphatase activity and leads to an increase in the hyperphosphorylated forms of the lysine-rich (F1) histone. Under normal conditions a massive phosphatase activity is triggered as the cells shift from M into G1 phase. In the presence of ZnCl2 this activity is abolished and thehyperphosphorylated form of F1 persists intact into G1. We have asked the simple question of whether the chromosome can still extend during the M-G1 transition even if the F1 histone is maintained in the hyperphosphorylated form. We observe an apparently normal extension os the chromosomal material under these conditions, though it is evident that high levels of ZnCl2 have rather substantial effects on other cell functions.", "contents": "Relationship between chromosome condensation and metaphase lysine-rich histone phosphorylation. Treatment of metaphase HTC cells with ZnCl2 inhibits histone phosphatase activity and leads to an increase in the hyperphosphorylated forms of the lysine-rich (F1) histone. Under normal conditions a massive phosphatase activity is triggered as the cells shift from M into G1 phase. In the presence of ZnCl2 this activity is abolished and thehyperphosphorylated form of F1 persists intact into G1. We have asked the simple question of whether the chromosome can still extend during the M-G1 transition even if the F1 histone is maintained in the hyperphosphorylated form. We observe an apparently normal extension os the chromosomal material under these conditions, though it is evident that high levels of ZnCl2 have rather substantial effects on other cell functions."} {"id": "PMID:1254650", "title": "The polymerization of actin. II. How nonfilamentous actin becomes nonrandomly distributed in sperm: evidence for the association of this actin with membranes.", "content": "At an early stage in spermiogenesis the acrosomal vacuole and other organelles including ribosomes are located at the basal end of the cell. From here actin must be transported to its future location at the anterior end of the cell. At no stage, in the accumulation of actin in the periacrosomal region is the actin sequested in a membrane-bounded compartment such as a vacuole or vesicle. Since filaments are not present in the periacrsomoal region during the accumulation of the actin even though the fixation of these cells is sufficiently good to distinguish actin filaments in thin section, the actin must accumulate in the nonfilamentous state.", "contents": "The polymerization of actin. II. How nonfilamentous actin becomes nonrandomly distributed in sperm: evidence for the association of this actin with membranes. At an early stage in spermiogenesis the acrosomal vacuole and other organelles including ribosomes are located at the basal end of the cell. From here actin must be transported to its future location at the anterior end of the cell. At no stage, in the accumulation of actin in the periacrosomal region is the actin sequested in a membrane-bounded compartment such as a vacuole or vesicle. Since filaments are not present in the periacrsomoal region during the accumulation of the actin even though the fixation of these cells is sufficiently good to distinguish actin filaments in thin section, the actin must accumulate in the nonfilamentous state."} {"id": "PMID:1254651", "title": "Morphological changes in tight junctions of Necturus maculosus proximal tubules undergoing saline diuresis.", "content": "Tight junctions between epithelial cells are believed to control the paracellular diffusion of substances across epithelia. Epithelia in which tight junctions are poorly developed display a higher paracellular electrical conductance, while those with extensive tight junctions show lower conductance values. We described here a particular epithelium, that of the proximal tubules of the Necturus kidney, in which the development of the tight junctions varies in parallel with a change of paracellular electrical conductance. In control conditions, tight junctions between epithelial cells of the proximal tubules are more developed than in tubules undergoing saline diuresis, a situation which increases the conductance across the paracellular shunt pathway.", "contents": "Morphological changes in tight junctions of Necturus maculosus proximal tubules undergoing saline diuresis. Tight junctions between epithelial cells are believed to control the paracellular diffusion of substances across epithelia. Epithelia in which tight junctions are poorly developed display a higher paracellular electrical conductance, while those with extensive tight junctions show lower conductance values. We described here a particular epithelium, that of the proximal tubules of the Necturus kidney, in which the development of the tight junctions varies in parallel with a change of paracellular electrical conductance. In control conditions, tight junctions between epithelial cells of the proximal tubules are more developed than in tubules undergoing saline diuresis, a situation which increases the conductance across the paracellular shunt pathway."} {"id": "PMID:1254652", "title": "Non-histone protein synthesis during G1 phase and its relation to DNA replication.", "content": "The kinetics of non-histone chromosomal protein (NHCP) synthesis were studied in Chinese hamster ovary (CHO) plateau phase cells stimulated to proliferate and were compared to NHCP synthesis kinetics in two populations of synchronous G1 traversing cells. In all cases, NHCP synthesis rates increase 3- to 5-fold as cells traversed G1 and attained maximum values one hour before semi-conservative DNA replication began. Similar to results in synchronous G1 cells, the molecular weight distributions of the NHCP fraction from stimulated plateau phase cells underwent only minor changes, measured by sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis, as these cells moved toward S phase. Yet, during this progression after plateau phase and in the transition from early G1 to late G1 in synchronous cells, the total NHCP fraction increased significantly (1.5-2-fold) in amount per cell. These data indicate that plateau phase cells are similar to early G1 cells both in terms of their amounts of non-histone per cell and in their subsequent NHCP synthesis kinetics as they move toward S phase. These results extend previous findings which suggested that NHCP synthesis was coupled to DNA replication and demonstrate that the increased NHCP synthesis and accumulation in chromatin may be a biochemical marker for G1 progression.", "contents": "Non-histone protein synthesis during G1 phase and its relation to DNA replication. The kinetics of non-histone chromosomal protein (NHCP) synthesis were studied in Chinese hamster ovary (CHO) plateau phase cells stimulated to proliferate and were compared to NHCP synthesis kinetics in two populations of synchronous G1 traversing cells. In all cases, NHCP synthesis rates increase 3- to 5-fold as cells traversed G1 and attained maximum values one hour before semi-conservative DNA replication began. Similar to results in synchronous G1 cells, the molecular weight distributions of the NHCP fraction from stimulated plateau phase cells underwent only minor changes, measured by sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis, as these cells moved toward S phase. Yet, during this progression after plateau phase and in the transition from early G1 to late G1 in synchronous cells, the total NHCP fraction increased significantly (1.5-2-fold) in amount per cell. These data indicate that plateau phase cells are similar to early G1 cells both in terms of their amounts of non-histone per cell and in their subsequent NHCP synthesis kinetics as they move toward S phase. These results extend previous findings which suggested that NHCP synthesis was coupled to DNA replication and demonstrate that the increased NHCP synthesis and accumulation in chromatin may be a biochemical marker for G1 progression."} {"id": "PMID:1254653", "title": "Effect of exogenous ATP on sodium transport in mammalian red cells.", "content": "The effect of exogenous adenosine triphosphate (ATP) and other nucleotides on the transport of Na in various mammalian red cells has been studied. While they have no effect on the transport of Na in human and cat red cells, in dog red cells adenosine and its mono-, di- and triphosphorylated forms were found to increase Na-influx. Of these, ATP has the most striking effect, causing a more than 8-fold increase at a concentration of 0.6 mM and exerting this effect at a dose range of 10(-5) to 10(-3) M. The effect of ATP is rapid (less than 5 minutes) and can be reversed by washing or the addition of calcium or magnesium. In contrast to the adenosine series other phosphorylated nucleotides (GTP, CTP, UDP, GDP and cAMP) have no effect. The well known volume dependent Na-transport in these cells is reversed in the presence of 0.6 mM ATP. It is suggested that ATP acts on passive cation movements either by chelation of membrane charge or by a direct interaction with membrane proteins and may be involved in the volume regulation of cation transport in the dog erythrocyte.", "contents": "Effect of exogenous ATP on sodium transport in mammalian red cells. The effect of exogenous adenosine triphosphate (ATP) and other nucleotides on the transport of Na in various mammalian red cells has been studied. While they have no effect on the transport of Na in human and cat red cells, in dog red cells adenosine and its mono-, di- and triphosphorylated forms were found to increase Na-influx. Of these, ATP has the most striking effect, causing a more than 8-fold increase at a concentration of 0.6 mM and exerting this effect at a dose range of 10(-5) to 10(-3) M. The effect of ATP is rapid (less than 5 minutes) and can be reversed by washing or the addition of calcium or magnesium. In contrast to the adenosine series other phosphorylated nucleotides (GTP, CTP, UDP, GDP and cAMP) have no effect. The well known volume dependent Na-transport in these cells is reversed in the presence of 0.6 mM ATP. It is suggested that ATP acts on passive cation movements either by chelation of membrane charge or by a direct interaction with membrane proteins and may be involved in the volume regulation of cation transport in the dog erythrocyte."} {"id": "PMID:1254654", "title": "Methionine metabolism in BHK cells: selection and characterization of ethionine resistant clones.", "content": "The selection of clones resistant to methionine antagonists was undertaken on baby hamster Kidney cells grown in a methionine free medium, supplemented with homocystine, folic acid and hydroxo-B12. Clones resistant to 30 mug/ml ethionine were isolated after mutagenesis at an induced mutation frequency of 2.3 X 10(-5). An ethionine resistant clone, ETH 304, was extensively studied. The resistant cells excreted methionine in the culture medium and the intracellular pools of methionine and SAM were two to five times greater in the resistant clone than in the wild type cells. A semidominant ethionine resistant phenotype was observed in hybrids between the wild type and this resistant clone. Measurement of the specific activity of menadione reductase, B12 methyltransferase and ATP: L-methionine S-adenosyl-transferase in crude extracts of the wild type showed a repressive action of methionine on the level of the three enzymes. However, the ethionine resistant clone ETH 304 was not modified in this function. Menadione reductase is feedback-inhibited by SAM in wild type cells. The enzyme of the ethionine resistant clone was significantly less sensitive to SAM. When a comparison of thermal stability was made between the wild type and ethionine resistant clone enzymes, it was found that the thermal stability of the latter was modified. Three other ethionine resistant clones, independantly isolated, were similarly affected in the properties of menadione reductase. These results suggest that the pathway of re-use of S-adenosyl homocysteine, produced during methylation reactions, is highly regulated by methionine and SAM.", "contents": "Methionine metabolism in BHK cells: selection and characterization of ethionine resistant clones. The selection of clones resistant to methionine antagonists was undertaken on baby hamster Kidney cells grown in a methionine free medium, supplemented with homocystine, folic acid and hydroxo-B12. Clones resistant to 30 mug/ml ethionine were isolated after mutagenesis at an induced mutation frequency of 2.3 X 10(-5). An ethionine resistant clone, ETH 304, was extensively studied. The resistant cells excreted methionine in the culture medium and the intracellular pools of methionine and SAM were two to five times greater in the resistant clone than in the wild type cells. A semidominant ethionine resistant phenotype was observed in hybrids between the wild type and this resistant clone. Measurement of the specific activity of menadione reductase, B12 methyltransferase and ATP: L-methionine S-adenosyl-transferase in crude extracts of the wild type showed a repressive action of methionine on the level of the three enzymes. However, the ethionine resistant clone ETH 304 was not modified in this function. Menadione reductase is feedback-inhibited by SAM in wild type cells. The enzyme of the ethionine resistant clone was significantly less sensitive to SAM. When a comparison of thermal stability was made between the wild type and ethionine resistant clone enzymes, it was found that the thermal stability of the latter was modified. Three other ethionine resistant clones, independantly isolated, were similarly affected in the properties of menadione reductase. These results suggest that the pathway of re-use of S-adenosyl homocysteine, produced during methylation reactions, is highly regulated by methionine and SAM."} {"id": "PMID:1254656", "title": "Bromodeoxyuridine induced variations in the level of alkaline phosphatase in several human heteroploid cell lines.", "content": "The level of alkaline phosphatase in a number of established cell lines of human origin can be modified by exposure to non-lethal concentrations of bromodeoxyuridine (BRdU). In the several cell lines examined an inverse relationship between amount of induction and constitutive level of the enzyme was observed. Thus, the H.Ep 2 line, which had the highest basal level of enzyme, was reversibly repressed following exposure to the drug, whereas other cell lines with relatively low constitutive enzyme levels were induced to a maximum of 10-fold following exposure. Initiation of induction required from 24 to 48 hours, and as short an exposure (\"pulse\") as five hours was sufficient to produce induction. Exposure to visible light had no effect upon the repression of alkaline phosphatase in H.Ep 2 by BRdU. Induction did not occur in non-dividing, serum starved cells. The time course of induction by BRdU and hydrocortisone was similar, and simultaneous exposure of the cells to both agents resulted in no greater induction than that observed with either drug alone. Experiments utilizing mitomycin C yielded significant induction in the presence of this agent alone, and somewhat less induction when both mitomycin C and BRdU were added simultaneously. These results suggest that DNA synthesis is required for BRdU were added simultaneously. These results suggest that DNA synthesis is required for BRdU-mediated induction of alkaline phosphatase.", "contents": "Bromodeoxyuridine induced variations in the level of alkaline phosphatase in several human heteroploid cell lines. The level of alkaline phosphatase in a number of established cell lines of human origin can be modified by exposure to non-lethal concentrations of bromodeoxyuridine (BRdU). In the several cell lines examined an inverse relationship between amount of induction and constitutive level of the enzyme was observed. Thus, the H.Ep 2 line, which had the highest basal level of enzyme, was reversibly repressed following exposure to the drug, whereas other cell lines with relatively low constitutive enzyme levels were induced to a maximum of 10-fold following exposure. Initiation of induction required from 24 to 48 hours, and as short an exposure (\"pulse\") as five hours was sufficient to produce induction. Exposure to visible light had no effect upon the repression of alkaline phosphatase in H.Ep 2 by BRdU. Induction did not occur in non-dividing, serum starved cells. The time course of induction by BRdU and hydrocortisone was similar, and simultaneous exposure of the cells to both agents resulted in no greater induction than that observed with either drug alone. Experiments utilizing mitomycin C yielded significant induction in the presence of this agent alone, and somewhat less induction when both mitomycin C and BRdU were added simultaneously. These results suggest that DNA synthesis is required for BRdU were added simultaneously. These results suggest that DNA synthesis is required for BRdU-mediated induction of alkaline phosphatase."} {"id": "PMID:1254659", "title": "Studies on steroids. CIX. O-omega-haloalkyloximes, new derivatives for gas chromatography-mass spectrometry of oxosteroids.", "content": "Several kinds of omega-haloalkoxyamines have been prepared as new derivative-forming agents applicable for the gas chromatography-mass spectrometry of carbonyl compounds. Of these reagents, 2-chloroethoxyamine hydrochloride [O-(2-chloroethyl)hydroxylamine] was the most suitable for use with oxosteroids because of its higher reactivity and the appropriate retention value and satisfactory chromatographic properties of the resulting oximes. The contribution to the retention value due to formation of the 2-chloroethyloxime was determined for 5alpha-androstanones having the oxo-group at various positions in the steroid nucleus. As expected, 17-oxosteroid O-2-haloethyloximes exhibit readily distinguishable isotope peaks as a cluster in the mas spectrum.", "contents": "Studies on steroids. CIX. O-omega-haloalkyloximes, new derivatives for gas chromatography-mass spectrometry of oxosteroids. Several kinds of omega-haloalkoxyamines have been prepared as new derivative-forming agents applicable for the gas chromatography-mass spectrometry of carbonyl compounds. Of these reagents, 2-chloroethoxyamine hydrochloride [O-(2-chloroethyl)hydroxylamine] was the most suitable for use with oxosteroids because of its higher reactivity and the appropriate retention value and satisfactory chromatographic properties of the resulting oximes. The contribution to the retention value due to formation of the 2-chloroethyloxime was determined for 5alpha-androstanones having the oxo-group at various positions in the steroid nucleus. As expected, 17-oxosteroid O-2-haloethyloximes exhibit readily distinguishable isotope peaks as a cluster in the mas spectrum."} {"id": "PMID:1254660", "title": "Separation of C19 and C21 dihydroxysteroids by open-hole tubular glass columns and lipophilic gel chromatography.", "content": "The combination of lipophilic gel chromatography and high-resolution glass capillary chromatography has been shown to be an important means of identification and quantification of steroid urinary metabolites. Some problems in the use of capillary columns, such as coating with polar and apolar stationary phases, column performance, thermal stability and injection systems have been investigated and this type of chromatography has been used in the analysis of 33 dihydroxysteroids. Gel chromatography is a method complementary to high-efficiency gas chromatography. The steroids are eluted according to the number of hydroxyl groups in the molecules.", "contents": "Separation of C19 and C21 dihydroxysteroids by open-hole tubular glass columns and lipophilic gel chromatography. The combination of lipophilic gel chromatography and high-resolution glass capillary chromatography has been shown to be an important means of identification and quantification of steroid urinary metabolites. Some problems in the use of capillary columns, such as coating with polar and apolar stationary phases, column performance, thermal stability and injection systems have been investigated and this type of chromatography has been used in the analysis of 33 dihydroxysteroids. Gel chromatography is a method complementary to high-efficiency gas chromatography. The steroids are eluted according to the number of hydroxyl groups in the molecules."} {"id": "PMID:1254661", "title": "Studies on monoterpene glucosides and related natural products. XXXI. Gas chromatography and gas chromatography-mass spectrometry of iridoid and secoiridoid glucosides.", "content": "A total of 33 iridoid and secoiridoid glucosides were detected by gas chromatography on several columns such as OV-1 or OV-17. Representative glucosides were then subjected to gas chromatography-mass spectrometry, giving some characteristic peaks that permitted the discrimination of both types of glucosides from other compounds in most instances. The successful detection of both types of glucosides in several plant extracts showed the applicability of this combination of methods to small amounts of plant materials.", "contents": "Studies on monoterpene glucosides and related natural products. XXXI. Gas chromatography and gas chromatography-mass spectrometry of iridoid and secoiridoid glucosides. A total of 33 iridoid and secoiridoid glucosides were detected by gas chromatography on several columns such as OV-1 or OV-17. Representative glucosides were then subjected to gas chromatography-mass spectrometry, giving some characteristic peaks that permitted the discrimination of both types of glucosides from other compounds in most instances. The successful detection of both types of glucosides in several plant extracts showed the applicability of this combination of methods to small amounts of plant materials."} {"id": "PMID:1254662", "title": "Quantitative thin-layer chromatographic analysis of ergotamine tartrate and caffeine in the nanogram range.", "content": "Direct, quantitative, thin-layer chromatographic methods for the determination of ergotamine tartrate and caffeine in the presence of each other in blood and in pharmaceutical preparations are described. The blood is centrifuged, the plasma decanted from the coagulum and deproteinized with acetone-methanol. After removal of the solvent mixture, the active ingredients are extracted from the remaining aqueous solution with chloroform. In the case of the pharmaceutical preparations, the active ingredients are also extracted with chloroform or methanol. Ergotamine tartrate and caffeine are separated on pre-coated silica gel 60 F254 plates and measured directly on the thin-layer plate, ergotamine tartrate being determined by the fluorescence method, excitation wavelength 365 nm, at lambdamax.=450 nm and caffeine by the reflactance method at lambdamax.=274 nm. The analytical methods are suitable for the bioavailability studies of these drugs in blood as they enable the determination of 20 ng ergotamine tartrate with a coefficient of variation of 6.7% and the determination of 200 ng caffeine with a coefficient of variation of 6.1%. The methods have also proved useful in the determination of the active ingredients of drug forms such as tablets and suppositories and can be well reproduced with a maximum coefficient of variation of 4.9% for ergotamine tartrate and 3.5% for caffeine.", "contents": "Quantitative thin-layer chromatographic analysis of ergotamine tartrate and caffeine in the nanogram range. Direct, quantitative, thin-layer chromatographic methods for the determination of ergotamine tartrate and caffeine in the presence of each other in blood and in pharmaceutical preparations are described. The blood is centrifuged, the plasma decanted from the coagulum and deproteinized with acetone-methanol. After removal of the solvent mixture, the active ingredients are extracted from the remaining aqueous solution with chloroform. In the case of the pharmaceutical preparations, the active ingredients are also extracted with chloroform or methanol. Ergotamine tartrate and caffeine are separated on pre-coated silica gel 60 F254 plates and measured directly on the thin-layer plate, ergotamine tartrate being determined by the fluorescence method, excitation wavelength 365 nm, at lambdamax.=450 nm and caffeine by the reflactance method at lambdamax.=274 nm. The analytical methods are suitable for the bioavailability studies of these drugs in blood as they enable the determination of 20 ng ergotamine tartrate with a coefficient of variation of 6.7% and the determination of 200 ng caffeine with a coefficient of variation of 6.1%. The methods have also proved useful in the determination of the active ingredients of drug forms such as tablets and suppositories and can be well reproduced with a maximum coefficient of variation of 4.9% for ergotamine tartrate and 3.5% for caffeine."} {"id": "PMID:1254668", "title": "Quantitative determination of naltrexone and beta-naltrexol in human plasma using electron detection.", "content": "A gas-liquid chromatographic method is described for the determination of naltrexone and beta-naltrexol in human plasma following derivatization with pentafluoropropionic anhydride using electron capture detection. The lower sensitivity of the method for absolute standards is 5-10 pg. Following an acute 100-mg dose to a subject, peak levels of naltrexone of 15 ng/ml at 2 h and of beta-naltrexol 84 ng/ml at 4 h were observed. The levels of both compounds decreased by 24 h after the dose: naltrexone to 2.9 ng/ml and beta-naltrexol to 25 ng/ml. Following chronic administration for two weeks of 100 mg per day the peak levels of naltrexone and betanaltrexol increased to 26.9 and 131 ng/ml at 2 h, respectively, but by 24 h both compounds were at levels similar to those following a single dose. Thus no accumulation of either drug ro metabolite in the plasma was seen following chronic naltrexone administration.", "contents": "Quantitative determination of naltrexone and beta-naltrexol in human plasma using electron detection. A gas-liquid chromatographic method is described for the determination of naltrexone and beta-naltrexol in human plasma following derivatization with pentafluoropropionic anhydride using electron capture detection. The lower sensitivity of the method for absolute standards is 5-10 pg. Following an acute 100-mg dose to a subject, peak levels of naltrexone of 15 ng/ml at 2 h and of beta-naltrexol 84 ng/ml at 4 h were observed. The levels of both compounds decreased by 24 h after the dose: naltrexone to 2.9 ng/ml and beta-naltrexol to 25 ng/ml. Following chronic administration for two weeks of 100 mg per day the peak levels of naltrexone and betanaltrexol increased to 26.9 and 131 ng/ml at 2 h, respectively, but by 24 h both compounds were at levels similar to those following a single dose. Thus no accumulation of either drug ro metabolite in the plasma was seen following chronic naltrexone administration."} {"id": "PMID:1254669", "title": "The application of thin-layer gel filtration chromatography in the rapid assessment of protein-protein coupling reactions.", "content": "The use of enzymes as markers when covalently coupled to various antigens or antibodies has wide application in medical science. A variety of bifunctional reagents has been used to produced the conjugates, and there have been some attempts to investigate the conditions of reaction necessary to obtain good coupling, whilst preserving the biological function of the molecules. The present study describes the influence of coupling conditions on the coupling of a alpha-amylase and albumin by a range of commercially available bifunctional coupling reagents, and the application of thin-layer gel filtration chromatography for the rapid qualitative/semi-quantitative assessment of coupling reactions.", "contents": "The application of thin-layer gel filtration chromatography in the rapid assessment of protein-protein coupling reactions. The use of enzymes as markers when covalently coupled to various antigens or antibodies has wide application in medical science. A variety of bifunctional reagents has been used to produced the conjugates, and there have been some attempts to investigate the conditions of reaction necessary to obtain good coupling, whilst preserving the biological function of the molecules. The present study describes the influence of coupling conditions on the coupling of a alpha-amylase and albumin by a range of commercially available bifunctional coupling reagents, and the application of thin-layer gel filtration chromatography for the rapid qualitative/semi-quantitative assessment of coupling reactions."} {"id": "PMID:1254670", "title": "Gas-liquid chromatographic method for the measurement of methyl urea in blood and urine.", "content": "A technique for the measurement of methyl urea in biological fluids is described based upon gas-liquid chromatography of its trifluoroacetyl derivative. The method requires 10 ml of either blood or urine and is capable of measuring methyl urea at concentrations of less than 5 mg/l.", "contents": "Gas-liquid chromatographic method for the measurement of methyl urea in blood and urine. A technique for the measurement of methyl urea in biological fluids is described based upon gas-liquid chromatography of its trifluoroacetyl derivative. The method requires 10 ml of either blood or urine and is capable of measuring methyl urea at concentrations of less than 5 mg/l."} {"id": "PMID:1254671", "title": "Determination of 7-iodo-1,3-dihydro-1-methyl-5(2'-fluorophenyl)-2h-1,4-benzodiazepin-2-one (Ro 7-9957) and its major biotransformation products in blood and urine by electron capture-gas-liquid chromatography.", "content": "A sensitive and specific electron capture-gas chromatographic assay was developed for the determination of 7-iodo-1,3-dihydro-1-methyl-5(2'-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I) and its major metabolites in blood and urine. The overall recovery of I and its N-desmethyl metabolite (II) from blood is apparently quantitative. The recovery of the major urinary metabolite, the N-desmethyl-3-hydroxy analog (IV), and the minor metabolites, the N-desmethyl analog (II) and the N-methyl-3-hydroxy analog (III) added to urine as authentic reference standards ranged from 80 to 85%. The sensitivity limits of detection are of the order of 2-3 ng of I and 4-5 ng of II per ml of blood or urine. The method was applied to the determination of blood levels and the urinary excretion pattern in a dog following oral and intravenous administration of a 1-mg/kg dose (total 13 mg), and in man following the intravenous administration of single 5- and 10-mg doses. The N-desmethyl metabolite II was more predominant in dog blood than was the orally or intravenously administered I, but II was barely measurable in human blood.", "contents": "Determination of 7-iodo-1,3-dihydro-1-methyl-5(2'-fluorophenyl)-2h-1,4-benzodiazepin-2-one (Ro 7-9957) and its major biotransformation products in blood and urine by electron capture-gas-liquid chromatography. A sensitive and specific electron capture-gas chromatographic assay was developed for the determination of 7-iodo-1,3-dihydro-1-methyl-5(2'-fluorophenyl)-2H-1,4-benzodiazepin-2-one (I) and its major metabolites in blood and urine. The overall recovery of I and its N-desmethyl metabolite (II) from blood is apparently quantitative. The recovery of the major urinary metabolite, the N-desmethyl-3-hydroxy analog (IV), and the minor metabolites, the N-desmethyl analog (II) and the N-methyl-3-hydroxy analog (III) added to urine as authentic reference standards ranged from 80 to 85%. The sensitivity limits of detection are of the order of 2-3 ng of I and 4-5 ng of II per ml of blood or urine. The method was applied to the determination of blood levels and the urinary excretion pattern in a dog following oral and intravenous administration of a 1-mg/kg dose (total 13 mg), and in man following the intravenous administration of single 5- and 10-mg doses. The N-desmethyl metabolite II was more predominant in dog blood than was the orally or intravenously administered I, but II was barely measurable in human blood."} {"id": "PMID:1254672", "title": "A specific gas chromatographic method for the determination of microsomal styrene monooxygenase and styrene epoxide hydratase activities.", "content": "A gas chromatographic (GC) method for the determination of the metabolite resulting from the activities of microsomal styrene monooxygenase (epoxide synthetase) and epoxide hydratase using styrene or styrene epoxide as substrates has been developed. The determination of the activities of both enzymes is based on the GC determination of phenylethylene glycol after its esterification with n-butylboronic acid. Kinetic parameters for both enzymes are given.", "contents": "A specific gas chromatographic method for the determination of microsomal styrene monooxygenase and styrene epoxide hydratase activities. A gas chromatographic (GC) method for the determination of the metabolite resulting from the activities of microsomal styrene monooxygenase (epoxide synthetase) and epoxide hydratase using styrene or styrene epoxide as substrates has been developed. The determination of the activities of both enzymes is based on the GC determination of phenylethylene glycol after its esterification with n-butylboronic acid. Kinetic parameters for both enzymes are given."} {"id": "PMID:1254673", "title": "Mass fragmentographic quantitation of glutamic acid and gamma-aminobutyric acid in cerebellar nuclei and sympathetic ganglia of rats.", "content": "A method for the simultaneous quantitation of glutamic acid and gamma-aminobutyric acid (GABA) in tissue by mass fragmentography has been developed. The amino and carboxylic groups of the two amino acids were in a convenient one-step reaction derivatized with pentafluoropropionic anhydride and hexafluoroisopropanol. Deuterium-labeled glutamic acid and GABA and a homologue of GABA have been used as internal standards. The usefulness of the technique has been demonstrated by measurements in parts of rat cerebellum and in the superior cervical ganglion.", "contents": "Mass fragmentographic quantitation of glutamic acid and gamma-aminobutyric acid in cerebellar nuclei and sympathetic ganglia of rats. A method for the simultaneous quantitation of glutamic acid and gamma-aminobutyric acid (GABA) in tissue by mass fragmentography has been developed. The amino and carboxylic groups of the two amino acids were in a convenient one-step reaction derivatized with pentafluoropropionic anhydride and hexafluoroisopropanol. Deuterium-labeled glutamic acid and GABA and a homologue of GABA have been used as internal standards. The usefulness of the technique has been demonstrated by measurements in parts of rat cerebellum and in the superior cervical ganglion."} {"id": "PMID:1254674", "title": "High-speed liquid chromatographic determination of phenylpyruvic acid.", "content": "A high-speed liquid chromatographic method has been developed for the determination of urinary phenylpyruvic acid. This acid is converted by treatment with naphthalene-2,3-diamine into 3-benzyl-2-hydroxybenzoquinoxaline, which is extracted into carbon tetrachloride for separation. 2-Mercaptoethanol is a useful stabilizer, and 2-chlorothioxanthone is a suitable internal standard. The method is specific, and the results are not affected by the presence of such 2-oxo-acids as pyruvic acid, 2-oxobutyric acid, 2-oxoglutaric acid, and 4-hydroxphenylpyruvic acid.", "contents": "High-speed liquid chromatographic determination of phenylpyruvic acid. A high-speed liquid chromatographic method has been developed for the determination of urinary phenylpyruvic acid. This acid is converted by treatment with naphthalene-2,3-diamine into 3-benzyl-2-hydroxybenzoquinoxaline, which is extracted into carbon tetrachloride for separation. 2-Mercaptoethanol is a useful stabilizer, and 2-chlorothioxanthone is a suitable internal standard. The method is specific, and the results are not affected by the presence of such 2-oxo-acids as pyruvic acid, 2-oxobutyric acid, 2-oxoglutaric acid, and 4-hydroxphenylpyruvic acid."} {"id": "PMID:1254680", "title": "Application of a computer-based chromatograph for automated water pollution analyses.", "content": "A modified head-space analysis technique, coupling thermal extraction with subsequent adsorption of organics on a poly (para 2,6-diphenyl phenylene) oxide adsorbent (Tenax-GC), has been found to be an efficacious tool when combined with gas chromatography for the study and monitoring of low molecular weight organics present in drinking water supplies (1-4). This procedure has allowed for the analysis of volatile organics in the low parts-per-billion range from 1 liter or less of tap water. Because thermal extraction requires smaller sample sizes than required in carbon-chloroform extraction methods and liquid/liquid extractions, the EPA has recently adopted this type of methodology (5,6). Passage of the Safe Water Drinking Act in December of 1974 has mandated that each state assumes the primary responsibility for carrying out the purposes of the legislation (7). Because the Act says that any supplier of water serving 25 individuals or more must comply with these regulations, large-scale monitoring programs will have to be undertaken. It was thus our desire to try to simplify the sample collection and data acquistion and reduction processes as much as possible, in the effort to make the procedure more adaptable for incorporation into routine monitoring programs. Also, automation reduces the experience and number of personnel required to perform the analyses. In addition to analysis of drinking water samples, the automated procedure described hereinafter can also be applied to monitoring industrial plant effluents, waste water treatment processes, and general quality control monitoring of low molecular weight organic compounds.", "contents": "Application of a computer-based chromatograph for automated water pollution analyses. A modified head-space analysis technique, coupling thermal extraction with subsequent adsorption of organics on a poly (para 2,6-diphenyl phenylene) oxide adsorbent (Tenax-GC), has been found to be an efficacious tool when combined with gas chromatography for the study and monitoring of low molecular weight organics present in drinking water supplies (1-4). This procedure has allowed for the analysis of volatile organics in the low parts-per-billion range from 1 liter or less of tap water. Because thermal extraction requires smaller sample sizes than required in carbon-chloroform extraction methods and liquid/liquid extractions, the EPA has recently adopted this type of methodology (5,6). Passage of the Safe Water Drinking Act in December of 1974 has mandated that each state assumes the primary responsibility for carrying out the purposes of the legislation (7). Because the Act says that any supplier of water serving 25 individuals or more must comply with these regulations, large-scale monitoring programs will have to be undertaken. It was thus our desire to try to simplify the sample collection and data acquistion and reduction processes as much as possible, in the effort to make the procedure more adaptable for incorporation into routine monitoring programs. Also, automation reduces the experience and number of personnel required to perform the analyses. In addition to analysis of drinking water samples, the automated procedure described hereinafter can also be applied to monitoring industrial plant effluents, waste water treatment processes, and general quality control monitoring of low molecular weight organic compounds."} {"id": "PMID:1254681", "title": "Improved column systems for gas-liquid chromatography of iproniazid and iproclozide.", "content": "As a result of a comparative study performed on thirteen liquid phases an improved set of four analytically packed columns, i.e., Versamid-900, Versamid-930, XE-60, and OV-225 is withheld for successful gas chromatography of iproniazid and iproclozide. Retention data in terms of adjusted retention times and relative retentions, using structurally related compounds as reference, are reported. An evaluation of gas chromatographic performance of proposed columns is described.", "contents": "Improved column systems for gas-liquid chromatography of iproniazid and iproclozide. As a result of a comparative study performed on thirteen liquid phases an improved set of four analytically packed columns, i.e., Versamid-900, Versamid-930, XE-60, and OV-225 is withheld for successful gas chromatography of iproniazid and iproclozide. Retention data in terms of adjusted retention times and relative retentions, using structurally related compounds as reference, are reported. An evaluation of gas chromatographic performance of proposed columns is described."} {"id": "PMID:1254686", "title": "Paget's disease of the bone: observations after cessation of long-term synthetic salmon calcitonin treatment.", "content": "Thirteen patients with Paget's disease of the bone were treated with subcutaneous injections of synthetic salmon calcitonin (SCT) for a mean period of 22 months at doses of 50-100 MCR units daily or 3 times a week. They manifested symptomatic improvement and significant reductions in serum alkaline phosphatase and urinary hydroxyproline excretion during SCT administration. Following discontinuation of SCT, symptomatic improvement was maintained in 10 patients for up to one year, whereas a recurrence of symptoms was seen in only 3 patients. The serum alkaline phosphatase generally showed a return toward pretreatment values 6 months after discontinuation of SCT, whereas urinary hydroxyproline remained depressed for up to a year.", "contents": "Paget's disease of the bone: observations after cessation of long-term synthetic salmon calcitonin treatment. Thirteen patients with Paget's disease of the bone were treated with subcutaneous injections of synthetic salmon calcitonin (SCT) for a mean period of 22 months at doses of 50-100 MCR units daily or 3 times a week. They manifested symptomatic improvement and significant reductions in serum alkaline phosphatase and urinary hydroxyproline excretion during SCT administration. Following discontinuation of SCT, symptomatic improvement was maintained in 10 patients for up to one year, whereas a recurrence of symptoms was seen in only 3 patients. The serum alkaline phosphatase generally showed a return toward pretreatment values 6 months after discontinuation of SCT, whereas urinary hydroxyproline remained depressed for up to a year."} {"id": "PMID:1254687", "title": "Androsterone sulfate concentrations in plasma in hypo- and hyperthyroidism.", "content": "Androsterone sulfate concentrations have been measured in the plasma of 16 hypothyroid women and 14 hyperthyroid women by a gas-liquid chromatographic technique and in 23 hypothyroid and 18 hyperthyroid women by radioimmunoassay. In obth studies androsterone sulfate concentrations were significantly higher in the hyperthyroid groups. In one hypothyroid subject, blood was obtained at 20-minute intervals over 24 hours before and after the administration of triiodothyronine; plasma androsterone sulfate, initially 25 mug per dl, increased three-fold as a consequence of treatment.", "contents": "Androsterone sulfate concentrations in plasma in hypo- and hyperthyroidism. Androsterone sulfate concentrations have been measured in the plasma of 16 hypothyroid women and 14 hyperthyroid women by a gas-liquid chromatographic technique and in 23 hypothyroid and 18 hyperthyroid women by radioimmunoassay. In obth studies androsterone sulfate concentrations were significantly higher in the hyperthyroid groups. In one hypothyroid subject, blood was obtained at 20-minute intervals over 24 hours before and after the administration of triiodothyronine; plasma androsterone sulfate, initially 25 mug per dl, increased three-fold as a consequence of treatment."} {"id": "PMID:1254688", "title": "Dose dependence of growth response to human growth hormone in growth hormone deficiency.", "content": "A trial of the relative effect on growth of 20 IU/week and 10 IU/week of human growth hormone has been made in 38 patients with \"isolated\" growth hormone deficiency over 1 year of treatment, 18 patients over 2 years and 10 over 3 years, and in 17 patients with surgically treated craniopharyngiomata over 1 year. The velocity of height growth in the first year of treatment, compared with a full year of pre-treatment control, was 1.3 times as great in both groups of patients on the larger dose as it was in those on the smaller one. Second-degree equations fitted to the treatment catch-up curve gave estimates of 1.7 cm more height gained on the larger dose by the end of the first year, 2.7 cm by the end of the second, and 3.4 cm by the end of the third. Adjusting treatment increment by covariance for bone age at the beginning of treatment, pre-treatment velocity, and body surface area did not alter these mean differences. Bone age velocity during treatment was the same in both treatment groups (mean 1.09 \"years\"/year in the first year); thus we anticipate a gain in final adult height of the order of 10 cm from employing the larger dose. The decrease in skin folds occurring on treatment, however, was no different with the larger than with the smaller dose. This reinforces previous observations that the short-term metabolic and longer-term auxologic effects of hGH are not necessarily related.", "contents": "Dose dependence of growth response to human growth hormone in growth hormone deficiency. A trial of the relative effect on growth of 20 IU/week and 10 IU/week of human growth hormone has been made in 38 patients with \"isolated\" growth hormone deficiency over 1 year of treatment, 18 patients over 2 years and 10 over 3 years, and in 17 patients with surgically treated craniopharyngiomata over 1 year. The velocity of height growth in the first year of treatment, compared with a full year of pre-treatment control, was 1.3 times as great in both groups of patients on the larger dose as it was in those on the smaller one. Second-degree equations fitted to the treatment catch-up curve gave estimates of 1.7 cm more height gained on the larger dose by the end of the first year, 2.7 cm by the end of the second, and 3.4 cm by the end of the third. Adjusting treatment increment by covariance for bone age at the beginning of treatment, pre-treatment velocity, and body surface area did not alter these mean differences. Bone age velocity during treatment was the same in both treatment groups (mean 1.09 \"years\"/year in the first year); thus we anticipate a gain in final adult height of the order of 10 cm from employing the larger dose. The decrease in skin folds occurring on treatment, however, was no different with the larger than with the smaller dose. This reinforces previous observations that the short-term metabolic and longer-term auxologic effects of hGH are not necessarily related."} {"id": "PMID:1254689", "title": "Growth hormone and insulin binding to human liver.", "content": "Specific binding of 125I-hGH to human liver was found in autopsy specimens from 12 to 15 patients. Specific binding was studied using a new technique employing 20 mu thich \"microslices\" cut on a cryostat. About 0.5 to 1 mg of tissue per assay tube makes feasible the study of small samples. The range of specific binding was 1.4 to 11.7% of 80,000 cpm 125I-hGH added expressed per mg dry weight of tissue. Specific binding was also demonstratable in homogenates and crude membrane preparations from liver. No correlation was seen between 125I-hGH binding and age, sex, or pathology in the series of patients studied. No specific binding of 125I-hGH was observed in lung, adrenal, spleen, or kidney, although all the tissues bound 125I-insulin. Of several species of growth hormone tested, only primate GH displaced 125I-hGH from its binding sites in human liver. No displacement was seen with ovine or human prolactin or with insulin. Primate placental lactogens had only 0.5-1.0% potency of native hGH in displacing 125I-hGH from human liver. Ungulate placental extracts, however, were equipotent with hGH in this respect.", "contents": "Growth hormone and insulin binding to human liver. Specific binding of 125I-hGH to human liver was found in autopsy specimens from 12 to 15 patients. Specific binding was studied using a new technique employing 20 mu thich \"microslices\" cut on a cryostat. About 0.5 to 1 mg of tissue per assay tube makes feasible the study of small samples. The range of specific binding was 1.4 to 11.7% of 80,000 cpm 125I-hGH added expressed per mg dry weight of tissue. Specific binding was also demonstratable in homogenates and crude membrane preparations from liver. No correlation was seen between 125I-hGH binding and age, sex, or pathology in the series of patients studied. No specific binding of 125I-hGH was observed in lung, adrenal, spleen, or kidney, although all the tissues bound 125I-insulin. Of several species of growth hormone tested, only primate GH displaced 125I-hGH from its binding sites in human liver. No displacement was seen with ovine or human prolactin or with insulin. Primate placental lactogens had only 0.5-1.0% potency of native hGH in displacing 125I-hGH from human liver. Ungulate placental extracts, however, were equipotent with hGH in this respect."} {"id": "PMID:1254690", "title": "Triiodothyronine and thyroxine in urine. I. Measurement and application.", "content": "Urinary triiodothyronine (T3) and thyroxine (T4) were measured by RIA, and T4 was also measured by competitive protein binding (CPB). pH 1-hydrolysable conjugates were 48% of total urinary T3, and enzyme- or pH 1-hydrolysable conjugates were 55% and 61% of total urinary T4. The mean unconjugated T3 excretion was 34.3 ng/h (0.99 mug T3/g creatinine) in normal subjects (no day-night rhythm found), 1.56 mug/g in late pregnancy, 0.82 mug/g in neonates (1-12 days), and was also unchanged in persons with high or low thyroxine-binding globulin (TBG). In thyrotoxicosis, mean T3 excretion was 281 ng/h, no values being in the normal range. In primary hypothyroidism it was 18.3 ng/h, but over half the values were in the normal range. The mean urinary unconjugated T4 was 82.2 ng/h (1.37 mug T4/g creatinine) in normal subjects, 1.6 mug/g in neonates, and unchanged in persons with high or low TBG, except that in pregnancy high values were compatible with increases protein excretion. Apparently increased day-time T4 excretion compared with night-time excretion may also be due to changes in protein excretion rate. The mean T4 in thyrotoxicosis was 337 ng/h (12% of values in the normal range) and 32.8 ng/h in primary hypothyroidism (over half the normal range). All the assays, especially that of T4 by CPB gave readings which were incorrect with protein concentrations above 100 mg/l. Urinary T3 and T4 assays for clinical purposes have few practical advantages over serum assays, despite the relationship of urine T3 and T4 to serum unbound levels.", "contents": "Triiodothyronine and thyroxine in urine. I. Measurement and application. Urinary triiodothyronine (T3) and thyroxine (T4) were measured by RIA, and T4 was also measured by competitive protein binding (CPB). pH 1-hydrolysable conjugates were 48% of total urinary T3, and enzyme- or pH 1-hydrolysable conjugates were 55% and 61% of total urinary T4. The mean unconjugated T3 excretion was 34.3 ng/h (0.99 mug T3/g creatinine) in normal subjects (no day-night rhythm found), 1.56 mug/g in late pregnancy, 0.82 mug/g in neonates (1-12 days), and was also unchanged in persons with high or low thyroxine-binding globulin (TBG). In thyrotoxicosis, mean T3 excretion was 281 ng/h, no values being in the normal range. In primary hypothyroidism it was 18.3 ng/h, but over half the values were in the normal range. The mean urinary unconjugated T4 was 82.2 ng/h (1.37 mug T4/g creatinine) in normal subjects, 1.6 mug/g in neonates, and unchanged in persons with high or low TBG, except that in pregnancy high values were compatible with increases protein excretion. Apparently increased day-time T4 excretion compared with night-time excretion may also be due to changes in protein excretion rate. The mean T4 in thyrotoxicosis was 337 ng/h (12% of values in the normal range) and 32.8 ng/h in primary hypothyroidism (over half the normal range). All the assays, especially that of T4 by CPB gave readings which were incorrect with protein concentrations above 100 mg/l. Urinary T3 and T4 assays for clinical purposes have few practical advantages over serum assays, despite the relationship of urine T3 and T4 to serum unbound levels."} {"id": "PMID:1254691", "title": "Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein.", "content": "Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4.", "contents": "Triiodothyronine and thyroxine in urine. II. Renal handling, and effect of urinary protein. Mean urinary clearances of T3 were 164 ml/min in normal subjects, 177 in pregnancy, 221 in thyrotoxicosis, 174 in hypothyroidism, and 194 in 3 persons with undetectable T4 but normal T3 levels. T4 clearances were 38 ml/min in normal subjects, 48 in thyrotoxicosis, and 138 in hypothyroidism. Low creatinine clearance was associated with low clearances of T4 and T3. The data suggest urinary excretion of T3 by glomerular filtration of serum unbound T3 with added tubular excretion; and T4 excretion by glomerular filtration of unbound T4 and tubular reabsorption. However, 3-9% of urinary T3 and 5-12% of urinary T4 were bound to urinary proteins, and increased protein excretion caused markedly increased T4 excretion. In addition, 52% of urinary T3 and 68% of urinary T4 were bound to other substances of approximate mol wt 500-2,000, which may influence tubular handling of T3 or T4."} {"id": "PMID:1254692", "title": "Plasma levels of 5alpha-androstane-3alpha,17beta-diol in boys during adolescent growth.", "content": "A radioimmunoassay using as antibody against testosterone-3-carboxymethyloxime-BSA is described for the measurement of androstanediol (5alpha-androstane-3alpha,17beta-diol) in human plasma. Sephadex LH 20-column chromatography was used to separate other steroids croos-reaching with the antibody from androstanediol. The sensitivity of the assay was 7 pg and the recovery of labelled androstanediol was 65.1%. The intra-assay coefficient of variation was 9.9%. The existence of 5alpha-androstane-3alpha,17beta-diol in the androstanediol fraction could be demonstrated by gas chromatography and mass spectrometry (GC-MS). Plasma concentration of this substance was measured in 53 normally developing pre-pubertal and pubertal boys and in 13 adult men. The mean concentrations significantly rose from puberty stage 1 to 2, and stage 2 to 3. Although there was no significant difference between the plasma concentrations at stages 3 and 4, an increment from stage 4 and 5 was highly significant. Levels in adult males were significantly higher than those in the stage 5 of normal puberty.", "contents": "Plasma levels of 5alpha-androstane-3alpha,17beta-diol in boys during adolescent growth. A radioimmunoassay using as antibody against testosterone-3-carboxymethyloxime-BSA is described for the measurement of androstanediol (5alpha-androstane-3alpha,17beta-diol) in human plasma. Sephadex LH 20-column chromatography was used to separate other steroids croos-reaching with the antibody from androstanediol. The sensitivity of the assay was 7 pg and the recovery of labelled androstanediol was 65.1%. The intra-assay coefficient of variation was 9.9%. The existence of 5alpha-androstane-3alpha,17beta-diol in the androstanediol fraction could be demonstrated by gas chromatography and mass spectrometry (GC-MS). Plasma concentration of this substance was measured in 53 normally developing pre-pubertal and pubertal boys and in 13 adult men. The mean concentrations significantly rose from puberty stage 1 to 2, and stage 2 to 3. Although there was no significant difference between the plasma concentrations at stages 3 and 4, an increment from stage 4 and 5 was highly significant. Levels in adult males were significantly higher than those in the stage 5 of normal puberty."} {"id": "PMID:1254693", "title": "RAdioimmunoassay of human proparathyroid hormone: analysis of hormone content in tissue extracts and in plasma.", "content": "A radioimmunoassay for human proparathyroid hormone (hProPTH) has been developed and applied to an evaluation of prohormone content in parathyroid tissues and in plasma.", "contents": "RAdioimmunoassay of human proparathyroid hormone: analysis of hormone content in tissue extracts and in plasma. A radioimmunoassay for human proparathyroid hormone (hProPTH) has been developed and applied to an evaluation of prohormone content in parathyroid tissues and in plasma."} {"id": "PMID:1254694", "title": "Histological studies of bone from normocalcemic post-menopausal osteoporotic patients with increased circulating parathyroid hormone.", "content": "Quantitative histological evaluations were made of nondecalcified iliac crest needle biopsies were obtained from 16 untreated, normocalcemic, normophosphatemic postmenopausal osteopenic females. Six of the patients had elevated circulating immunoreactive parathyroid hormone. Morphometric parameters, which were significantly increased in the hyperparathyroid group compared with the euparathyroid patients were the cortical osteoclast count and the percentage of trabecular surface covered by active or inactive osteoid. In addition, in all patients, the cortical osteoclast count, and the per cent of trabecular surface covered by osteoid and inactive osteoid were directly related to levels of immunoreactive parathyroid hormone. These data suggest that progressive osteopenia in some patients with crush fracture, or postmenopausal or senile osteoporosis, may be conditioned by an osteoclastosis, elevations in circulating parathyroid hormone, and a relative increase in poorly mineralized osteoid tissue. As such they emphasize the heterogeneity of a so-called \"osteoporotic population\" and stress the need for specific histological morphometric evaluation of bone before initiating long-term therapeutic modalities.", "contents": "Histological studies of bone from normocalcemic post-menopausal osteoporotic patients with increased circulating parathyroid hormone. Quantitative histological evaluations were made of nondecalcified iliac crest needle biopsies were obtained from 16 untreated, normocalcemic, normophosphatemic postmenopausal osteopenic females. Six of the patients had elevated circulating immunoreactive parathyroid hormone. Morphometric parameters, which were significantly increased in the hyperparathyroid group compared with the euparathyroid patients were the cortical osteoclast count and the percentage of trabecular surface covered by active or inactive osteoid. In addition, in all patients, the cortical osteoclast count, and the per cent of trabecular surface covered by osteoid and inactive osteoid were directly related to levels of immunoreactive parathyroid hormone. These data suggest that progressive osteopenia in some patients with crush fracture, or postmenopausal or senile osteoporosis, may be conditioned by an osteoclastosis, elevations in circulating parathyroid hormone, and a relative increase in poorly mineralized osteoid tissue. As such they emphasize the heterogeneity of a so-called \"osteoporotic population\" and stress the need for specific histological morphometric evaluation of bone before initiating long-term therapeutic modalities."} {"id": "PMID:1254695", "title": "Measurements of free thyroxine: comparison of per cent of free thyroxine in diluted and undiluted sera.", "content": "The effect of dilution on values of the per cent of free T4 in serum (%FT4) measured by equilibrium dialysis, was determined by comparing the values for %FT4 in diluted and undiluted specimens. The specimens studied were sera obtained from 10 normal subjects, 10 patients with hyperthyroidism, 5 with hypothyroidism, and 9 women with normal pregnancy. The method of analysis employed was that described by Sterling and Brenner, except that the 125I-thyroxine used was predialyzed to remove non-thyroxine contaminants and that \"corrected\" values for %FT4 were calculated by dividing measured values by the numerical extent to which the serum had been diluted.", "contents": "Measurements of free thyroxine: comparison of per cent of free thyroxine in diluted and undiluted sera. The effect of dilution on values of the per cent of free T4 in serum (%FT4) measured by equilibrium dialysis, was determined by comparing the values for %FT4 in diluted and undiluted specimens. The specimens studied were sera obtained from 10 normal subjects, 10 patients with hyperthyroidism, 5 with hypothyroidism, and 9 women with normal pregnancy. The method of analysis employed was that described by Sterling and Brenner, except that the 125I-thyroxine used was predialyzed to remove non-thyroxine contaminants and that \"corrected\" values for %FT4 were calculated by dividing measured values by the numerical extent to which the serum had been diluted."} {"id": "PMID:1254696", "title": "Pituitary gonadotropin function during human pregnancy: serum FSH and LH levels before and after LHRH administration.", "content": "Pituitary gonadotropin reserve was evaluated in 8 normal pregnant women (13-35 weeks gestation) by measuring serum concentrations of FSH and LH (betaLH assay) before and after an IV bolus of 100 mug LHRH. Basal levels of FSH and LH were low or undetectable. LHRH administration failed to stimulate FSH release but did result in a small short-lived rise in LH levels. These findings provide further evidence that pituitary gonadotropin synthesis and release are inhibited during pregnancy.", "contents": "Pituitary gonadotropin function during human pregnancy: serum FSH and LH levels before and after LHRH administration. Pituitary gonadotropin reserve was evaluated in 8 normal pregnant women (13-35 weeks gestation) by measuring serum concentrations of FSH and LH (betaLH assay) before and after an IV bolus of 100 mug LHRH. Basal levels of FSH and LH were low or undetectable. LHRH administration failed to stimulate FSH release but did result in a small short-lived rise in LH levels. These findings provide further evidence that pituitary gonadotropin synthesis and release are inhibited during pregnancy."} {"id": "PMID:1254698", "title": "A pressor formation by trypsin from renin-denatured human plasma protein.", "content": "Trypsin, when incubated with human plasma protein either undenatured or denatured by pretreatment with acid or alkali or by heat, produced an angiotensin II-like pressor substance instead of the depressor bradykinin which has been reported to be formed from various plasma fractions and trypsin. This reaction may be due to the activation of prorenin by trypsin, but this is rather unlikely since it appears that angiotensin II rather than I is formed. It seems to be more likely a direct production of the angiotensin hormone from the substrate, and we propose to call tentatively the active product \"tryptensin\".", "contents": "A pressor formation by trypsin from renin-denatured human plasma protein. Trypsin, when incubated with human plasma protein either undenatured or denatured by pretreatment with acid or alkali or by heat, produced an angiotensin II-like pressor substance instead of the depressor bradykinin which has been reported to be formed from various plasma fractions and trypsin. This reaction may be due to the activation of prorenin by trypsin, but this is rather unlikely since it appears that angiotensin II rather than I is formed. It seems to be more likely a direct production of the angiotensin hormone from the substrate, and we propose to call tentatively the active product \"tryptensin\"."} {"id": "PMID:1254699", "title": "Effect of pyridoxine on human hypophyseal trophic hormone release: a possible stimulation of hypothalamic dopaminergic pathway.", "content": "A single dose of pyridoxine (300 mg iv) produced significant rises in peak levels of immunoreactive growth hormone GH and significant decrease of plasma prolactin PRL in 8 hospitalized healthy subjects. Serum glucose, luteinizing hormone LH, follicle stimulating hormone FSH and thyrotropin TSH were not altered significantly. In addition, in 5 acromegalic patients who were studied with both L-dopa and pyridoxine, inhibition of GH secretion followed either agent in a similar pattern. These data suggest a hypothalamic dopaminergic effect of pyridoxine.", "contents": "Effect of pyridoxine on human hypophyseal trophic hormone release: a possible stimulation of hypothalamic dopaminergic pathway. A single dose of pyridoxine (300 mg iv) produced significant rises in peak levels of immunoreactive growth hormone GH and significant decrease of plasma prolactin PRL in 8 hospitalized healthy subjects. Serum glucose, luteinizing hormone LH, follicle stimulating hormone FSH and thyrotropin TSH were not altered significantly. In addition, in 5 acromegalic patients who were studied with both L-dopa and pyridoxine, inhibition of GH secretion followed either agent in a similar pattern. These data suggest a hypothalamic dopaminergic effect of pyridoxine."} {"id": "PMID:1254700", "title": "Preparation and properties of a national reference endotoxin.", "content": "A large pool of refined endotoxin was prepared from Escherichia coli O113 by extraction with hot acqueous phenol. It was characterized chemically and biologically and will be available for a reference standard designated as reference endotoxin EC.", "contents": "Preparation and properties of a national reference endotoxin. A large pool of refined endotoxin was prepared from Escherichia coli O113 by extraction with hot acqueous phenol. It was characterized chemically and biologically and will be available for a reference standard designated as reference endotoxin EC."} {"id": "PMID:1254701", "title": "Ethylenimine-inactivated rabies vaccine of tissue culture origin.", "content": "The replication of seven rabies virus strains (CVS, HEP, PV, ERA, WIRAB, CPZ and BOLIVAR) in BHK cells and the inactivation dynamics of these strains by beta-propiolactone, acetylethylenimine, and ethylenimine were studied to find the most immunogenic strain and the most economic and stable inactivating agent for the production of an inactivated tissue culture rabies vaccine for animal use. The seven strains reached the peak of virus production 3 to 5 days after inoculation of the cell culture; PV yielded the highest virus titer (10(9) plaque-forming units/ml). The infectivity of virus suspensions containing 10(7) to 10(8) plaque-forming units/0.1 ml was inactivated by beta-propiolactone in 0.5 h, acetylethylenimine in 3.0 h, and ethylenimine in 1.0 h. Most of the vaccine lots prepared with the different strains and inactivating agents passed a modified National Institutes of Health potency test. The vaccines prepared with the PV strain had consistently higher antigenic values (equal or better than four) than the other six strains. This difference was highly significant (F6,12=59.8), whereas there were no statistically significant differences among the antigenic values of the vaccine lots prepared with the three inactivating agents. Batches of lyophilized and liquid vaccine stored at 4 C maintained potency for over 1 year. Ten dogs vaccinated with a vaccine prepared with the PV strain and inactivated with ethylenimine developed a good antibody response and resisted challenge 60 days after vaccination, while seven of eight nonvaccinated controls died of rabies. This information indicates that an inactivated, stable, economic, and easy-to-prepare rabies vaccine can be produced in BHK cells by using the PV strain and ethylenimine as an inactivating agent.", "contents": "Ethylenimine-inactivated rabies vaccine of tissue culture origin. The replication of seven rabies virus strains (CVS, HEP, PV, ERA, WIRAB, CPZ and BOLIVAR) in BHK cells and the inactivation dynamics of these strains by beta-propiolactone, acetylethylenimine, and ethylenimine were studied to find the most immunogenic strain and the most economic and stable inactivating agent for the production of an inactivated tissue culture rabies vaccine for animal use. The seven strains reached the peak of virus production 3 to 5 days after inoculation of the cell culture; PV yielded the highest virus titer (10(9) plaque-forming units/ml). The infectivity of virus suspensions containing 10(7) to 10(8) plaque-forming units/0.1 ml was inactivated by beta-propiolactone in 0.5 h, acetylethylenimine in 3.0 h, and ethylenimine in 1.0 h. Most of the vaccine lots prepared with the different strains and inactivating agents passed a modified National Institutes of Health potency test. The vaccines prepared with the PV strain had consistently higher antigenic values (equal or better than four) than the other six strains. This difference was highly significant (F6,12=59.8), whereas there were no statistically significant differences among the antigenic values of the vaccine lots prepared with the three inactivating agents. Batches of lyophilized and liquid vaccine stored at 4 C maintained potency for over 1 year. Ten dogs vaccinated with a vaccine prepared with the PV strain and inactivated with ethylenimine developed a good antibody response and resisted challenge 60 days after vaccination, while seven of eight nonvaccinated controls died of rabies. This information indicates that an inactivated, stable, economic, and easy-to-prepare rabies vaccine can be produced in BHK cells by using the PV strain and ethylenimine as an inactivating agent."} {"id": "PMID:1254702", "title": "Recovery of pathogenic fungi from clinical specimens submitted for mycobacteriological culture.", "content": "A total of 332 major pathogenic fungi were isolated from specimens cultured onto both fungal culture media and media used for culturing mycobacteria from January 1968 to June 1975. Only 72 (21.7%) fungi were recovered on media used for culturing mycobacteria. The effect of sodium hydroxide treatment was evaluated and shown to be detrimental to the recovery of fungi. It is recommended that clinical laboratories not rely on mycobacteriological cultures to recover fungal pathogens.", "contents": "Recovery of pathogenic fungi from clinical specimens submitted for mycobacteriological culture. A total of 332 major pathogenic fungi were isolated from specimens cultured onto both fungal culture media and media used for culturing mycobacteria from January 1968 to June 1975. Only 72 (21.7%) fungi were recovered on media used for culturing mycobacteria. The effect of sodium hydroxide treatment was evaluated and shown to be detrimental to the recovery of fungi. It is recommended that clinical laboratories not rely on mycobacteriological cultures to recover fungal pathogens."} {"id": "PMID:1254703", "title": "Pseudomonas cepacia strains isolated from water reservoirs of unheated nebulizers.", "content": "Pseudomonas cepacia strains were isolated from the water reservoirs of unheated nebulizers in a hospital setting. The isolates were characterized by morphology, biochemical tests, and antibiotic susceptibility patterns. An interesting feature of these organisms was their capacity for sustained multiplication in either doubly deionized or doubly distilled water as well as 5% dextrose or 0.9% saline. They could not multiply in doubly deionized and then doubly distilled water or in any of several parenteral nutrition solutions studied. Isolation of Pseudomonas cepacia from the water reservoirs of unheated nebulizers suggests that this equipment may serve as a source of respiratory tract exposure to the organism.", "contents": "Pseudomonas cepacia strains isolated from water reservoirs of unheated nebulizers. Pseudomonas cepacia strains were isolated from the water reservoirs of unheated nebulizers in a hospital setting. The isolates were characterized by morphology, biochemical tests, and antibiotic susceptibility patterns. An interesting feature of these organisms was their capacity for sustained multiplication in either doubly deionized or doubly distilled water as well as 5% dextrose or 0.9% saline. They could not multiply in doubly deionized and then doubly distilled water or in any of several parenteral nutrition solutions studied. Isolation of Pseudomonas cepacia from the water reservoirs of unheated nebulizers suggests that this equipment may serve as a source of respiratory tract exposure to the organism."} {"id": "PMID:1254704", "title": "Unusual Chromobacterium violaceum: aerogenic strains.", "content": "This is the first report of Chromobacterium violaceum strains that are aerogenic. Two pigmented strains of C. violaceum and their nonpigmented variants produced gas in glucose broth. Kliger iron agar, and triple sugar iron agar. They were similar morphologically and biochemically to other anaerogenic strains studied previously.", "contents": "Unusual Chromobacterium violaceum: aerogenic strains. This is the first report of Chromobacterium violaceum strains that are aerogenic. Two pigmented strains of C. violaceum and their nonpigmented variants produced gas in glucose broth. Kliger iron agar, and triple sugar iron agar. They were similar morphologically and biochemically to other anaerogenic strains studied previously."} {"id": "PMID:1254705", "title": "Isolation and characterization of a catalase-negative strain of Staphylococcus aureus.", "content": "An unusual, naturally occurring strain of Staphylococcus aureus is characterized. It is typical in colony and cellular morphology, coagulase production, and other biochemical reactions as compared to S. aureus (ATCC-25923), except that it is catalase negative and fails to ferment mannitol anaerobically.", "contents": "Isolation and characterization of a catalase-negative strain of Staphylococcus aureus. An unusual, naturally occurring strain of Staphylococcus aureus is characterized. It is typical in colony and cellular morphology, coagulase production, and other biochemical reactions as compared to S. aureus (ATCC-25923), except that it is catalase negative and fails to ferment mannitol anaerobically."} {"id": "PMID:1254706", "title": "Meningitis due to Aeromonas hydrophila.", "content": "A case of meningitis caused by Aeromonas hydrophila is reported. The infection complicated an otherwise successful frontotemporal craniotomy. Survey of the literature revealed that human infections due to this organism are relatively uncommon, and its causal relationship in meningitis has not been previously reported. A. hydrophila is known to cause bacteremia in patients under treatment with immunosuppresive agents. We report meningitis with bacteremia, caused by this organism, in an immunologically competent host.", "contents": "Meningitis due to Aeromonas hydrophila. A case of meningitis caused by Aeromonas hydrophila is reported. The infection complicated an otherwise successful frontotemporal craniotomy. Survey of the literature revealed that human infections due to this organism are relatively uncommon, and its causal relationship in meningitis has not been previously reported. A. hydrophila is known to cause bacteremia in patients under treatment with immunosuppresive agents. We report meningitis with bacteremia, caused by this organism, in an immunologically competent host."} {"id": "PMID:1254707", "title": "Computer-assisted bacterial identification utilizing antimicrobial susceptibility profiles generated by autobac 1.", "content": "A computer program was developed to identify bacteria solely on the basis of their relative susceptibility to various antimicrobial agents. A sample of 481 clinical isolates from nine of the most commonly isolated gram-negative groups was identified by the quadratic discriminant function technique. Various combinations of antimicrobials were tried, and one set of 18 resulted in a more than 97% correlation with conventional identification procedures. The antimicrobial set could be decreased to 14, while a better than 95% correlation with the conventional procedures was maintained.", "contents": "Computer-assisted bacterial identification utilizing antimicrobial susceptibility profiles generated by autobac 1. A computer program was developed to identify bacteria solely on the basis of their relative susceptibility to various antimicrobial agents. A sample of 481 clinical isolates from nine of the most commonly isolated gram-negative groups was identified by the quadratic discriminant function technique. Various combinations of antimicrobials were tried, and one set of 18 resulted in a more than 97% correlation with conventional identification procedures. The antimicrobial set could be decreased to 14, while a better than 95% correlation with the conventional procedures was maintained."} {"id": "PMID:1254708", "title": "Cholesterol requirement of mycoplasmas as determined by microtiter test using polyene antibiotics.", "content": "A microtiter metabolic inhibition test was used to determine the effect of filipin and lucensomycin on the growth of representative species of Mycoplasma and Acholeplasma. The cholesterol-requiring species tested were found to be very susceptible to the two antibiotics, whereas the cholesterol nonrequiring species were not. The utilization of this method for differentiation between the Mycoplasma and Acholeplasma species is suggested and its advantages are discussed.", "contents": "Cholesterol requirement of mycoplasmas as determined by microtiter test using polyene antibiotics. A microtiter metabolic inhibition test was used to determine the effect of filipin and lucensomycin on the growth of representative species of Mycoplasma and Acholeplasma. The cholesterol-requiring species tested were found to be very susceptible to the two antibiotics, whereas the cholesterol nonrequiring species were not. The utilization of this method for differentiation between the Mycoplasma and Acholeplasma species is suggested and its advantages are discussed."} {"id": "PMID:1254709", "title": "Temperature-dependent cultural and biochemical characteristics of rhamnose-positive Yersinia enterocolitica.", "content": "Clinical isolates of rhamnose-positive Yersinia enterocolitica (Y.e.rh+) were compared with typical rhamnose-negative Y. enterocolitica (Y.e.rh-) and with Yersinia pseudotuberculosis. The Y.e.rh+ differed from the Y.e.rh- and Y. pseudotuberculosis in their ability to ferment raffinose and lactose, utilize citrate and in their inability to grow on Hektoen enteric agar at 22 or 37 C, on Salmonella-Shigella agar at 37 C, and scant on xylose-lysine-deoxycholate agar at 37 C. An extensive temperature-dependent profile of characteristics was established for the Y.e.rh+: motility, acetoin production, citrate utilization, growth on Salmonella-Shigella agar, and ampicillin resistance occurred at 22 C but not 37 C; fermentation of melibiose, raffinose, and cellobiose occurred within 24 h at 22 C, but not before 5 days at 37 C; fermentation of rhamnose and production of beta-galactosidase occurred within 24 h at 22 C, but not before 48 h at 37 C; greater resistance to ampicillin, chloramphenicol, streptomycin, kanamycin, carbenicillin, and gentamicin was observed at 22 than 37 C; and good growth on xylose-lysine-deoxycholate agar occurred at 22 but not 37 C. For optimal recovery of Y.e.rh+ from mixed culture, e.g., stools, two MacConkey plates should be inoculated and incubated, one at 37 C, and one at 22 C. Lactose-negative colonies appearing after 48 h on the 22 C MacConkey agar but not the 37 C MacConkey agar should be considered possible Y.e.rh+. Biochemicals should be tested in duplicate, one set incubated at 22 C, one set at 37 C. Antibiotic susceptibility tests of Y.e.rh+ isolates should be incubated at both 37 C and at a lower temperature to allow the greatest expression of resistance of these organisms to the various antibiotics.", "contents": "Temperature-dependent cultural and biochemical characteristics of rhamnose-positive Yersinia enterocolitica. Clinical isolates of rhamnose-positive Yersinia enterocolitica (Y.e.rh+) were compared with typical rhamnose-negative Y. enterocolitica (Y.e.rh-) and with Yersinia pseudotuberculosis. The Y.e.rh+ differed from the Y.e.rh- and Y. pseudotuberculosis in their ability to ferment raffinose and lactose, utilize citrate and in their inability to grow on Hektoen enteric agar at 22 or 37 C, on Salmonella-Shigella agar at 37 C, and scant on xylose-lysine-deoxycholate agar at 37 C. An extensive temperature-dependent profile of characteristics was established for the Y.e.rh+: motility, acetoin production, citrate utilization, growth on Salmonella-Shigella agar, and ampicillin resistance occurred at 22 C but not 37 C; fermentation of melibiose, raffinose, and cellobiose occurred within 24 h at 22 C, but not before 5 days at 37 C; fermentation of rhamnose and production of beta-galactosidase occurred within 24 h at 22 C, but not before 48 h at 37 C; greater resistance to ampicillin, chloramphenicol, streptomycin, kanamycin, carbenicillin, and gentamicin was observed at 22 than 37 C; and good growth on xylose-lysine-deoxycholate agar occurred at 22 but not 37 C. For optimal recovery of Y.e.rh+ from mixed culture, e.g., stools, two MacConkey plates should be inoculated and incubated, one at 37 C, and one at 22 C. Lactose-negative colonies appearing after 48 h on the 22 C MacConkey agar but not the 37 C MacConkey agar should be considered possible Y.e.rh+. Biochemicals should be tested in duplicate, one set incubated at 22 C, one set at 37 C. Antibiotic susceptibility tests of Y.e.rh+ isolates should be incubated at both 37 C and at a lower temperature to allow the greatest expression of resistance of these organisms to the various antibiotics."} {"id": "PMID:1254710", "title": "Survival of anaerobic and aerobic bacteria in a nonsupportive gassed transport system.", "content": "Survival of anaerobic and aerobic bacteria in a commercially available, non-supportive, gassed (oxygen-free) transport container (Anaport) was evaluated quantitatively. Saline-suspended obligate anaerobes survived significantly better in the gassed container in aerobic control tubes (P less than 0.025, t test), and counts were virtually unchanged after 8 h of holding. Similarly, initial counts and relative proportions of a mixture of Bacteroides fragilis and Staphylococcus aureus were maintained for 72 h. The value of the gassed transport system was less apparent when microorganisms were suspended in nutrient broth. The major advantage of the gassed transport system appears to be for holding of specimens collected by saline irrigation.", "contents": "Survival of anaerobic and aerobic bacteria in a nonsupportive gassed transport system. Survival of anaerobic and aerobic bacteria in a commercially available, non-supportive, gassed (oxygen-free) transport container (Anaport) was evaluated quantitatively. Saline-suspended obligate anaerobes survived significantly better in the gassed container in aerobic control tubes (P less than 0.025, t test), and counts were virtually unchanged after 8 h of holding. Similarly, initial counts and relative proportions of a mixture of Bacteroides fragilis and Staphylococcus aureus were maintained for 72 h. The value of the gassed transport system was less apparent when microorganisms were suspended in nutrient broth. The major advantage of the gassed transport system appears to be for holding of specimens collected by saline irrigation."} {"id": "PMID:1254711", "title": "Anaerobes survive in clinical specimens despite delayed processing.", "content": "Quantitative cultures were performed on 11 purulent specimens of at least 2 ml from mixed aerobic-anaerobic infections to determine the effect of prolonged exposure to air on the recovery of anaerobes. The specimens were processed immediately and after air exposure for periods of 10 min and 1, 4, and 24 h. There were at total of 37 anaerobic and 36 aerobic strains recovered from these specimens. Of the anaerobes, 26 were isolated with the initial processing and 22 were still present after air exposure for 24 h. The numerical concentrations of anaerobes showed little change with the sequential samplings. Eleven anaerobic strains were not detected in the initial culture but appeared sporadically in subsequent cultures. Using the types of specimens and method of processing employed in this study, most pathogenic anaerobes survived in purulent exudate despite extended periods of air exposure. The major cause of discrepent results with periodic cultures was attributed to vagaries in sampling.", "contents": "Anaerobes survive in clinical specimens despite delayed processing. Quantitative cultures were performed on 11 purulent specimens of at least 2 ml from mixed aerobic-anaerobic infections to determine the effect of prolonged exposure to air on the recovery of anaerobes. The specimens were processed immediately and after air exposure for periods of 10 min and 1, 4, and 24 h. There were at total of 37 anaerobic and 36 aerobic strains recovered from these specimens. Of the anaerobes, 26 were isolated with the initial processing and 22 were still present after air exposure for 24 h. The numerical concentrations of anaerobes showed little change with the sequential samplings. Eleven anaerobic strains were not detected in the initial culture but appeared sporadically in subsequent cultures. Using the types of specimens and method of processing employed in this study, most pathogenic anaerobes survived in purulent exudate despite extended periods of air exposure. The major cause of discrepent results with periodic cultures was attributed to vagaries in sampling."} {"id": "PMID:1254712", "title": "Evaluation of the rapid decarboxylase and dihydrolase test for the differentiation of nonfermentative bacteria.", "content": "A rapid medium for the detection of lysine and ornithine decarboxylase and arginine dihydrolase activity of 439 strains of gram-negative, nonfermenting bacteria was evaluated and compared with Moeller decarboxylase medium. Results were obtained in 4 to 24 h using the rapid medium, whereas Moeller medium often required extended (3 to 7 days) incubation. There was 100% agreement in the lysine tests with both media and almost 100% agreement in the ornithine tests. There was 91% agreement in the arginine tests, with the significance of discrepant results discussed. The sensitivity, specificity, and quick results obtained by the rapid test make it a suitable substitute for Moeller medium for the identication of gram-negative, nonfermenting bacteria.", "contents": "Evaluation of the rapid decarboxylase and dihydrolase test for the differentiation of nonfermentative bacteria. A rapid medium for the detection of lysine and ornithine decarboxylase and arginine dihydrolase activity of 439 strains of gram-negative, nonfermenting bacteria was evaluated and compared with Moeller decarboxylase medium. Results were obtained in 4 to 24 h using the rapid medium, whereas Moeller medium often required extended (3 to 7 days) incubation. There was 100% agreement in the lysine tests with both media and almost 100% agreement in the ornithine tests. There was 91% agreement in the arginine tests, with the significance of discrepant results discussed. The sensitivity, specificity, and quick results obtained by the rapid test make it a suitable substitute for Moeller medium for the identication of gram-negative, nonfermenting bacteria."} {"id": "PMID:1254713", "title": "Blocking effect of rheumatoid factor and cold agglutinins on complement fixation tests for histoplasmosis.", "content": "The blocking effect of rheumatoid factor (RF) and cold agglutinins (CA) on the detection of complement-fixing (CF) antibodies for Histoplasma capsulatum using a mycelial (histoplasmin) and a yeast antigen was studied. Sera from 213 patients serologically positive for histoplasmosis were screened for the presence of RF or CA. CF antibodies to H. capsulatum in sera containing RF or CA were studied before and after removal of these factors (RF and CA) by treatment with dithiothreitol. Results suggest that RF or CA may interfere with the CF reaction to the yeast antigen of H. capsulatum but not to the mycelial antigen (histoplasmin).", "contents": "Blocking effect of rheumatoid factor and cold agglutinins on complement fixation tests for histoplasmosis. The blocking effect of rheumatoid factor (RF) and cold agglutinins (CA) on the detection of complement-fixing (CF) antibodies for Histoplasma capsulatum using a mycelial (histoplasmin) and a yeast antigen was studied. Sera from 213 patients serologically positive for histoplasmosis were screened for the presence of RF or CA. CF antibodies to H. capsulatum in sera containing RF or CA were studied before and after removal of these factors (RF and CA) by treatment with dithiothreitol. Results suggest that RF or CA may interfere with the CF reaction to the yeast antigen of H. capsulatum but not to the mycelial antigen (histoplasmin)."} {"id": "PMID:1254714", "title": "Evaluation of simplified dichotomous schemata for the identification of anaerobic bacteria from clinical material.", "content": "Simplified dichotomous schemata are described for the identification of anaerobic bacteria commonly encountered in clinical material. The procedures used are combinations of routine biochemical tests and techniques that are used to uniformly characterize these organisms. Over 200 anaerobic organisms were used in a three-stage evaluation in which data were compared with those obtained by conventional methods. When there was inconsistency between the biochemical tests described in the presumptive identification schemes and gas-liquid chromatography, additional biochemical tests or reference procedures were used to confirm identification. Strains from the American Type Culture Collection and the Center for Disease Control, as well as recent clinical isolates, were included in this evaluation. The results show the simplified procedures to be useful for the identification of anaerobic isolates from clinical material.", "contents": "Evaluation of simplified dichotomous schemata for the identification of anaerobic bacteria from clinical material. Simplified dichotomous schemata are described for the identification of anaerobic bacteria commonly encountered in clinical material. The procedures used are combinations of routine biochemical tests and techniques that are used to uniformly characterize these organisms. Over 200 anaerobic organisms were used in a three-stage evaluation in which data were compared with those obtained by conventional methods. When there was inconsistency between the biochemical tests described in the presumptive identification schemes and gas-liquid chromatography, additional biochemical tests or reference procedures were used to confirm identification. Strains from the American Type Culture Collection and the Center for Disease Control, as well as recent clinical isolates, were included in this evaluation. The results show the simplified procedures to be useful for the identification of anaerobic isolates from clinical material."} {"id": "PMID:1254715", "title": "Comparative evaluation of the Candida agglutinin test, precipitin test, and germ tube dispersion test in the diagnosis of candidiasis.", "content": "Normal sera and sera from burned patients were examined for Candida agglutinin titers, precipitin titers, and the ability to disperse germ tubes of Candida albicans in an attempt to determine whether germ tube dispersion is correlated with Candida infection as animal models have indicated. Other investigators have reported that immunoglobulin G antibody to Candida interferes with a serum clumping factor resulting in germ tube dispersion. Germ tube dispersion in sera from burned patients with varying degrees of Candida infection is significantly greater than that found in uninfected controls. In addition, the germ tube dispersion test indicated the presence of Candida infection in several patients who had clinical evidence of infection but no detectable agglutinins or precipitins.", "contents": "Comparative evaluation of the Candida agglutinin test, precipitin test, and germ tube dispersion test in the diagnosis of candidiasis. Normal sera and sera from burned patients were examined for Candida agglutinin titers, precipitin titers, and the ability to disperse germ tubes of Candida albicans in an attempt to determine whether germ tube dispersion is correlated with Candida infection as animal models have indicated. Other investigators have reported that immunoglobulin G antibody to Candida interferes with a serum clumping factor resulting in germ tube dispersion. Germ tube dispersion in sera from burned patients with varying degrees of Candida infection is significantly greater than that found in uninfected controls. In addition, the germ tube dispersion test indicated the presence of Candida infection in several patients who had clinical evidence of infection but no detectable agglutinins or precipitins."} {"id": "PMID:1254716", "title": "Electron capture gas chromatography study of the acid and alcohol products of Clostridium septicum and Clostridium chauvoei.", "content": "The metabolic products produced by several strains of Clostridium septicum obtained from patients and animals, along with strains of Clostridium chauvoei, were studied in chopped meat glucose medium by electron capture gas-liquid chromatography (EC-GLC). The strains of C. septicum and C. chauvoei were shown to comprise five different metabolic groups. Both the EC-GLC study and the O and H antigenic study performed previously showed that strains of C. septicum comprise a heterogeneous group. One type of metabolic profile was found only in strains of C. chauvoei. The O antigen types and EC-GLC metabolic types of C. septicum correlated fairly well in isolates from cancer patients but not in stock culture and animal isolates.", "contents": "Electron capture gas chromatography study of the acid and alcohol products of Clostridium septicum and Clostridium chauvoei. The metabolic products produced by several strains of Clostridium septicum obtained from patients and animals, along with strains of Clostridium chauvoei, were studied in chopped meat glucose medium by electron capture gas-liquid chromatography (EC-GLC). The strains of C. septicum and C. chauvoei were shown to comprise five different metabolic groups. Both the EC-GLC study and the O and H antigenic study performed previously showed that strains of C. septicum comprise a heterogeneous group. One type of metabolic profile was found only in strains of C. chauvoei. The O antigen types and EC-GLC metabolic types of C. septicum correlated fairly well in isolates from cancer patients but not in stock culture and animal isolates."} {"id": "PMID:1254717", "title": "Rapid in vitro conversion and identification of Coccidioides immitis.", "content": "Since many contaminating nonpathogenic fungi resemble Coccidioides immitis culturally, isolates from patients must be inoculated into laboratory animals to confirem identification as C. immitis. This procedure is time-consuming, expensive, and not generally available in clinical laboratories. When cultures of C. immitis were grown in slide cultures on modified Converse liquid medium in purified agar and incubated at 40 C in a candle jar, all 57 isolates demonstrated inhibition of mycelial growth and conversion of arthrospores to endosporulating spherules in 3 to 5 days. Representative isolates of six species of nonpathogenic fungi that resembled C. immitis culturally either did not grow or failed to produce endosporulating spherules under the same conditions. This procedure is recommended for confirming the identication of a culture as C. immitis.", "contents": "Rapid in vitro conversion and identification of Coccidioides immitis. Since many contaminating nonpathogenic fungi resemble Coccidioides immitis culturally, isolates from patients must be inoculated into laboratory animals to confirem identification as C. immitis. This procedure is time-consuming, expensive, and not generally available in clinical laboratories. When cultures of C. immitis were grown in slide cultures on modified Converse liquid medium in purified agar and incubated at 40 C in a candle jar, all 57 isolates demonstrated inhibition of mycelial growth and conversion of arthrospores to endosporulating spherules in 3 to 5 days. Representative isolates of six species of nonpathogenic fungi that resembled C. immitis culturally either did not grow or failed to produce endosporulating spherules under the same conditions. This procedure is recommended for confirming the identication of a culture as C. immitis."} {"id": "PMID:1254718", "title": "A new medium for the detection of gelatin-hydrolyzing activity of human dental plaque flora.", "content": "A new medium for the detection of gelatin-hydrolyzing activity of human dental plaque flora by a simplified plate method is described. It is designed to support the growth of obligate anaerobes, facultative anaerobes, and aerobes. This medium can be used for the identification of gelatinase-producing organisms of clinical importance.", "contents": "A new medium for the detection of gelatin-hydrolyzing activity of human dental plaque flora. A new medium for the detection of gelatin-hydrolyzing activity of human dental plaque flora by a simplified plate method is described. It is designed to support the growth of obligate anaerobes, facultative anaerobes, and aerobes. This medium can be used for the identification of gelatinase-producing organisms of clinical importance."} {"id": "PMID:1254719", "title": "Comparison of sodium amylosulfate and sodium polyanetholsulfonate in blood culture media.", "content": "A comparison between sodium polyanetholsulfonate and sodium amylosulfate in unvented vacuum blood culture bottles containing tryptic soy broth was made with 5,800 sets of blood cultures. No statistically significant differences in isolation rates of bacteria were noted.", "contents": "Comparison of sodium amylosulfate and sodium polyanetholsulfonate in blood culture media. A comparison between sodium polyanetholsulfonate and sodium amylosulfate in unvented vacuum blood culture bottles containing tryptic soy broth was made with 5,800 sets of blood cultures. No statistically significant differences in isolation rates of bacteria were noted."} {"id": "PMID:1254720", "title": "Phage typing set for group C1 and C2 Salmonellae.", "content": "Fifteen common serotypes representative of group C(1) and C(2)Salmonella were characterized using a single set of phages.", "contents": "Phage typing set for group C1 and C2 Salmonellae. Fifteen common serotypes representative of group C(1) and C(2)Salmonella were characterized using a single set of phages."} {"id": "PMID:1254721", "title": "Effectiveness of palladium chloride for the isolation of anaerobes.", "content": "Because of the increased price of palladium chloride, we investigated the effectiveness of the addition of this ingredient to the culture medium used for the recovery of anaerobes. With our system, the addition of palladium chloride did not consistently improve the recovery rate of bacteria from guinea pig intestinal contents and human fecal material.", "contents": "Effectiveness of palladium chloride for the isolation of anaerobes. Because of the increased price of palladium chloride, we investigated the effectiveness of the addition of this ingredient to the culture medium used for the recovery of anaerobes. With our system, the addition of palladium chloride did not consistently improve the recovery rate of bacteria from guinea pig intestinal contents and human fecal material."} {"id": "PMID:1254722", "title": "Prophylactic immunization of humans against rabies by intradermal inoculation of human diploid cell culture vaccine.", "content": "The antirabies human diploid cell vaccine produced by 1'Institute Merieux, Lyon, France, was administered intradermally to 35 high-risk volunteers using 0.2-ml amounts and various immunization schedules. Three groups never before vaccinated against rabies developed virus-neutralizing antibodies, the titer of which was dose dependent. A single injection stimulated the formation of antibodies. Four inoculations induced the highest antibody levels and the longest persistence of antibody. The administration of a single intradermal booster inoculation was sufficient, even in the case of low-persisting antibody, to elicit a rapid increase of antibodies to high levels. A primary inoculation course of two injections induced a sufficient antibody level which, in case of exposure, could apparently be rapidly elevated by a 0.2-ml intradermal booster inoculation. Adverse side reactions were observed in 7 of 14 individuals after a 1- or 1.5-year intradermal booster inoculation. We therefore suggest that the intramuscular and subcutaneous routes continue to be used for primary vaccinations and that the highly effective intradermal route be restricted to booster inoculations. This is the first long term study of this vaccine and should be a guideline for the pre-exposure treatment of high-risk personnel.", "contents": "Prophylactic immunization of humans against rabies by intradermal inoculation of human diploid cell culture vaccine. The antirabies human diploid cell vaccine produced by 1'Institute Merieux, Lyon, France, was administered intradermally to 35 high-risk volunteers using 0.2-ml amounts and various immunization schedules. Three groups never before vaccinated against rabies developed virus-neutralizing antibodies, the titer of which was dose dependent. A single injection stimulated the formation of antibodies. Four inoculations induced the highest antibody levels and the longest persistence of antibody. The administration of a single intradermal booster inoculation was sufficient, even in the case of low-persisting antibody, to elicit a rapid increase of antibodies to high levels. A primary inoculation course of two injections induced a sufficient antibody level which, in case of exposure, could apparently be rapidly elevated by a 0.2-ml intradermal booster inoculation. Adverse side reactions were observed in 7 of 14 individuals after a 1- or 1.5-year intradermal booster inoculation. We therefore suggest that the intramuscular and subcutaneous routes continue to be used for primary vaccinations and that the highly effective intradermal route be restricted to booster inoculations. This is the first long term study of this vaccine and should be a guideline for the pre-exposure treatment of high-risk personnel."} {"id": "PMID:1254723", "title": "The essentiality of insulin and the role of glucagon in regulating glucose utilization and production during strenuous exercise in dogs.", "content": "In order to elucidate the role of insulin and glucagon during strenuous exercise (100 m/min, slope 10-12 degrees), we have determined the rates of production (Ra), utilization (Rd), and metabolic clearance (M) of glucose in normal dogs before pancreatectomy and 2 wk after total pancreatectomy (a) when they were being maintained on constant intraportal basal insulin infusion, (245 muU/kg-min) and (b) when insulin supply had been withheld before and during exercise. Such an intense exercise induced in normal dogs a prompt decrease in mean immunoreactive serum insulin (IRI) from 20 +/- 3 to 11 +/- 2 muU/ml. In depancreatized insulin-infused dogs serum IRI during rest and exercise was between 14 +/- 1 and 12 +/- 2 muU/ml. In the third group, after cessation of insulin infusion, IRI decreased by 76% (from 17 +/- 5 to 4 +/- 1) and did not decrease futher during exercise. During exercise, serum immunoreactive glucagon (IRG) increased threefold in normal dogs. In depancreatized dogs serum IRG was the same as in normal resting dogs (indicating a nonpancreatic source of the hormone) but it did not increase during exercise. In normal dogs exercise induced proportional increases in Ra, Rd, and M (threefold) and normoglycemia was maintained. Changes in glucose turnover in depancreatized insulin-infused dogs were similar to those seen in normal dogs suggesting that a decrease in insulin secretion and a rise in IRG are not essential to prevent hypoglycemia in diabetic dogs. With the cessation of insulin infusion in resting depancreatized dogs, Ra increased, M decreased, and hyperglycemia ensued. During exercise, Ra continued to rise, but M did not increase significantly. (a) Regulation of glucose production by liver during exercise is multifactorial. A decrease in IRI and an increase in IRG are not the only factors which can promote delivery of glucose to the peripheral tissues. The insulin glucagon molar ratio was found not to be an essential metabolic functional unit in regulating glucose metabolism during exercise. (b) It is hypothesized that increases in blood flow and capillary surface area can lead to an increase in the amount of insulin delivered to the muscle even when serum levels of IRI are reduced during exercies. It is suggested that small, but adequate amounts of insulin (as found in normal and depancreatized insulin-infused dogs) are essential in regulating glucose uptake in the working muscle. (c) Since totally depancreatized dogs had normal serum levels of IRG (originating presumably from the gastrointestinal tract), the question of essentiality of basal glucagon activity in glucose homeostasis during exercise could not be resolved by these experiments. It appears, however, that regulation of secretion of nonpancreatic glucagon differs from that of pancreatic glucagon.", "contents": "The essentiality of insulin and the role of glucagon in regulating glucose utilization and production during strenuous exercise in dogs. In order to elucidate the role of insulin and glucagon during strenuous exercise (100 m/min, slope 10-12 degrees), we have determined the rates of production (Ra), utilization (Rd), and metabolic clearance (M) of glucose in normal dogs before pancreatectomy and 2 wk after total pancreatectomy (a) when they were being maintained on constant intraportal basal insulin infusion, (245 muU/kg-min) and (b) when insulin supply had been withheld before and during exercise. Such an intense exercise induced in normal dogs a prompt decrease in mean immunoreactive serum insulin (IRI) from 20 +/- 3 to 11 +/- 2 muU/ml. In depancreatized insulin-infused dogs serum IRI during rest and exercise was between 14 +/- 1 and 12 +/- 2 muU/ml. In the third group, after cessation of insulin infusion, IRI decreased by 76% (from 17 +/- 5 to 4 +/- 1) and did not decrease futher during exercise. During exercise, serum immunoreactive glucagon (IRG) increased threefold in normal dogs. In depancreatized dogs serum IRG was the same as in normal resting dogs (indicating a nonpancreatic source of the hormone) but it did not increase during exercise. In normal dogs exercise induced proportional increases in Ra, Rd, and M (threefold) and normoglycemia was maintained. Changes in glucose turnover in depancreatized insulin-infused dogs were similar to those seen in normal dogs suggesting that a decrease in insulin secretion and a rise in IRG are not essential to prevent hypoglycemia in diabetic dogs. With the cessation of insulin infusion in resting depancreatized dogs, Ra increased, M decreased, and hyperglycemia ensued. During exercise, Ra continued to rise, but M did not increase significantly. (a) Regulation of glucose production by liver during exercise is multifactorial. A decrease in IRI and an increase in IRG are not the only factors which can promote delivery of glucose to the peripheral tissues. The insulin glucagon molar ratio was found not to be an essential metabolic functional unit in regulating glucose metabolism during exercise. (b) It is hypothesized that increases in blood flow and capillary surface area can lead to an increase in the amount of insulin delivered to the muscle even when serum levels of IRI are reduced during exercies. It is suggested that small, but adequate amounts of insulin (as found in normal and depancreatized insulin-infused dogs) are essential in regulating glucose uptake in the working muscle. (c) Since totally depancreatized dogs had normal serum levels of IRG (originating presumably from the gastrointestinal tract), the question of essentiality of basal glucagon activity in glucose homeostasis during exercise could not be resolved by these experiments. It appears, however, that regulation of secretion of nonpancreatic glucagon differs from that of pancreatic glucagon."} {"id": "PMID:1254724", "title": "Is gastrin a major determinant of basal lower esophageal sphincter pressure? A double-blind controlled study using high titer gastrin antiserum.", "content": "Studies were performed in anesthetized opossums to determine the influence of binding of circulating gastrin with a high titer gastrin antiserum on lower esophageal sphincter pressure. Gastrin antiserum or control antiserum was administered intravenously in successive doses of 0.02, 0.1, and 0.5 ml/kg on separate days. The lower esophageal sphincter pressures were measured for 1 h before and for 1 h after antiserum administration. The control serum caused no binding of opossum circulating gastrin, nor did it modify lower esophageal sphincter pressure. On the other hand, the administration of gastrin antiserum resulted in the binding of 85-90% of circulating gastrin, but it did not reduce sphincter pressure. A continuous infusion of 0.25 mug-kg-1-h-1 of synthetic human gastrin I caused a significant (P less than 0.05) increase in the sphincter pressure, a 30-fold increase in gastric acid output, and a fourfold increase in immunoreactive gastrin in the opossum blood. Prior treatment with 0.1 ml/kg of gastrin antiserum antagonized and 0.2 ml/kg of the antiserum abolished the gastrin-stimulated gastric acid secretion and the stimulating effect of gastrin on lower esophageal sphincter pressure. However, neither dose of antiserum modified basal lower esophageal sphincter pressure. It is concluded that circulating gastrin may be an important determinant of basal sphincter pressure.", "contents": "Is gastrin a major determinant of basal lower esophageal sphincter pressure? A double-blind controlled study using high titer gastrin antiserum. Studies were performed in anesthetized opossums to determine the influence of binding of circulating gastrin with a high titer gastrin antiserum on lower esophageal sphincter pressure. Gastrin antiserum or control antiserum was administered intravenously in successive doses of 0.02, 0.1, and 0.5 ml/kg on separate days. The lower esophageal sphincter pressures were measured for 1 h before and for 1 h after antiserum administration. The control serum caused no binding of opossum circulating gastrin, nor did it modify lower esophageal sphincter pressure. On the other hand, the administration of gastrin antiserum resulted in the binding of 85-90% of circulating gastrin, but it did not reduce sphincter pressure. A continuous infusion of 0.25 mug-kg-1-h-1 of synthetic human gastrin I caused a significant (P less than 0.05) increase in the sphincter pressure, a 30-fold increase in gastric acid output, and a fourfold increase in immunoreactive gastrin in the opossum blood. Prior treatment with 0.1 ml/kg of gastrin antiserum antagonized and 0.2 ml/kg of the antiserum abolished the gastrin-stimulated gastric acid secretion and the stimulating effect of gastrin on lower esophageal sphincter pressure. However, neither dose of antiserum modified basal lower esophageal sphincter pressure. It is concluded that circulating gastrin may be an important determinant of basal sphincter pressure."} {"id": "PMID:1254725", "title": "Spontaneous in vivo isomerization of bovine serum albumin as a determinant of its normal catabolism.", "content": "By combination of isoelectric focusing and immunoelectrophoresis of fresh bovine plasma it is shown that 10% of the albumin in plasma has isoionic points equal to the intramolecular SS-interchanged isomers of bovine serum albumin (BSA). It is also shown that (a) albumin with the isoionic point of SS-interchanged BSA is produced in the cow from radioiodinated BSA depleted from SS-interchanged albumin before injection and (b) purified radiolabeled SS-interchanged BSA can be converted in vivo to albumin with the native isoionic point. On this basis, it is proposed that SS-interchanged albumin in vivo is in postsynthetic equilibrium with the \"native\" albumin conformation. The SS-interchanged isomers purified either from commerical BSA or from BSA submitted to SH-SS interchange was, after radioiodination with 125I, compared metabolically with \"native\" albumin labeled with 131I in the same calf. Both species of SS-interchanged albumins have fast initial turnover rates but obtain a normal rate of degradation after the reversion to native albumin. If the isomers formed in vivo have the same properties as the ones present in commercial BSA, at least 50% of the physiological degradation of albumin can be accounted for by the 6-7 times faster catabolic rates of these isomers.", "contents": "Spontaneous in vivo isomerization of bovine serum albumin as a determinant of its normal catabolism. By combination of isoelectric focusing and immunoelectrophoresis of fresh bovine plasma it is shown that 10% of the albumin in plasma has isoionic points equal to the intramolecular SS-interchanged isomers of bovine serum albumin (BSA). It is also shown that (a) albumin with the isoionic point of SS-interchanged BSA is produced in the cow from radioiodinated BSA depleted from SS-interchanged albumin before injection and (b) purified radiolabeled SS-interchanged BSA can be converted in vivo to albumin with the native isoionic point. On this basis, it is proposed that SS-interchanged albumin in vivo is in postsynthetic equilibrium with the \"native\" albumin conformation. The SS-interchanged isomers purified either from commerical BSA or from BSA submitted to SH-SS interchange was, after radioiodination with 125I, compared metabolically with \"native\" albumin labeled with 131I in the same calf. Both species of SS-interchanged albumins have fast initial turnover rates but obtain a normal rate of degradation after the reversion to native albumin. If the isomers formed in vivo have the same properties as the ones present in commercial BSA, at least 50% of the physiological degradation of albumin can be accounted for by the 6-7 times faster catabolic rates of these isomers."} {"id": "PMID:1254726", "title": "Intrarenal mechanisms of salt retention after bile duct ligation in rats.", "content": "In order to study renal salt-retaining mechanisms during the early stages of ascites formation, rats were subjected to bile duct ligation. After this procedure, plasma volumes were found to be reduced and hematocrits slightly increased. The whole-kidney glomberular filtration rate and plasma flows were reduced to 59 and 57% of control values, but the filtration fraction was unchanged. Absolute sodium excretion, as well as the fraction of the filtered sodium load excreted, was also significantly reduced. When micropuncture techniques were used to examine the function of single superficial nephrons, the glomerular filtration rate in these nephrons was found to be reduced to 70% of controlled values, and fractional reabsorption was found to be increased at all accessible sites along the nephron. Filtration by intermediate and juxtamedullary nephrons, determined by Hanssen's technique, was reduced to 55 and 48% of control values. By the use of radioactive microspheres, it was demonstrated that blood flow to superficial, intermediate, and juxtamedullary nephrons was reduced to 49, 59, and 73% of control values. Filtration by superficial nephrons decreased much more than plasma flow--a finding which suggests that the measured increase in fractional reabsorption was associated with an increase in the superficial nephron filtration fraction. From this study, it appears that two factors play an important part in the sodium retention observed in the initial stages of ascites formation following bile duct ligation in rats: (a) a decrease in the filtered sodium load and (b) increased fractional reabsorption by the superficial nephrons--the nephrons which show the least decrease in filtration.", "contents": "Intrarenal mechanisms of salt retention after bile duct ligation in rats. In order to study renal salt-retaining mechanisms during the early stages of ascites formation, rats were subjected to bile duct ligation. After this procedure, plasma volumes were found to be reduced and hematocrits slightly increased. The whole-kidney glomberular filtration rate and plasma flows were reduced to 59 and 57% of control values, but the filtration fraction was unchanged. Absolute sodium excretion, as well as the fraction of the filtered sodium load excreted, was also significantly reduced. When micropuncture techniques were used to examine the function of single superficial nephrons, the glomerular filtration rate in these nephrons was found to be reduced to 70% of controlled values, and fractional reabsorption was found to be increased at all accessible sites along the nephron. Filtration by intermediate and juxtamedullary nephrons, determined by Hanssen's technique, was reduced to 55 and 48% of control values. By the use of radioactive microspheres, it was demonstrated that blood flow to superficial, intermediate, and juxtamedullary nephrons was reduced to 49, 59, and 73% of control values. Filtration by superficial nephrons decreased much more than plasma flow--a finding which suggests that the measured increase in fractional reabsorption was associated with an increase in the superficial nephron filtration fraction. From this study, it appears that two factors play an important part in the sodium retention observed in the initial stages of ascites formation following bile duct ligation in rats: (a) a decrease in the filtered sodium load and (b) increased fractional reabsorption by the superficial nephrons--the nephrons which show the least decrease in filtration."} {"id": "PMID:1254727", "title": "Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat.", "content": "The effects of both synthetic and biologically produced angiotensin II (AII) upon the process of glolerular filtration were examined in the plasma-expanded (2.5% body wt) Munich-Wistar rat, by micropuncture evaluation of pressures, nephron plasma flow (rpf) and filtration rate (sngfr). Plasma expansion was chosen as a control condition because (a) response to AII was uniform and predictable, (b) endogenous generation of AII was presumably suppressed, and (c) the high control values for rpf permitted accurate determination of values for the glomerular permeability coefficient (LpA) before and during AII infusion. With subpressor quantities of synthetic Asn-1, Val-5 AII (less than 5 ng/100 g body wt/min), sngfr fell from 47.7 in the control group to 39.8 nl/min/g kidney (P less than 0.005). The rpf fell to 60% of control values (P less than 0.001). Measurement of glomerular capillary (PG) and Bowman's space (Pt) hydrostatic pressures in surface glomeruli with a servo-nulling device permitted evaluation of the hydrostatic pressure gradient (deltaP = PG - Pi). DeltaP increased from 38.1 +/- 1.2 in control to 45.9 +/- 1.3 mm Hg after Asn-1, Val-5 AII and essentially neutralized the effect of decreased rpf in sngfr. The sngfr then fell as a result of a decreased in LpA from 0.063 +/- 0.008 in control to 0.028 +/- 0.004 nl/s/g kidney/mm Hg after Asn-1, Val-5 AII (P less than 0.02). Lower doses of Asp-1, Ile-5 AII (less than 3 ng/100 g body wt/min) had no effect on sngfr, rpf, deltaP, and afferent and efferent vascular resistance, but significantly elevated systemic blood pressure, suggesting peripheral effects on smooth muscle at this low dose. LpA was 0.044 +/- 0.007 nl/s/g kidney/mm Hg after low-dose Asp-1, Ile-5 AII, and 0.063 +/- 0.008 in the control group (0.02 greater than P greater than 0.1). Higher, equally pressor doses of native AII (5 ng/100 g body wt/min) produced effects almost identical to similar quantites of synthetic Asn-1, Val-5 AII upon rpf, deltaP, sngfr, and renal vascular resistance. LpA again fell to 0.026 +/- 0.004 nl/s/g kidney/mn Hg, a value almost identical to that after the synthetic AII. Paired studies with Asp-1, Ile-5 AII also demonstrated a consistent reduction in LpA.", "contents": "Angiotensin II effects upon the glomerular microcirculation and ultrafiltration coefficient of the rat. The effects of both synthetic and biologically produced angiotensin II (AII) upon the process of glolerular filtration were examined in the plasma-expanded (2.5% body wt) Munich-Wistar rat, by micropuncture evaluation of pressures, nephron plasma flow (rpf) and filtration rate (sngfr). Plasma expansion was chosen as a control condition because (a) response to AII was uniform and predictable, (b) endogenous generation of AII was presumably suppressed, and (c) the high control values for rpf permitted accurate determination of values for the glomerular permeability coefficient (LpA) before and during AII infusion. With subpressor quantities of synthetic Asn-1, Val-5 AII (less than 5 ng/100 g body wt/min), sngfr fell from 47.7 in the control group to 39.8 nl/min/g kidney (P less than 0.005). The rpf fell to 60% of control values (P less than 0.001). Measurement of glomerular capillary (PG) and Bowman's space (Pt) hydrostatic pressures in surface glomeruli with a servo-nulling device permitted evaluation of the hydrostatic pressure gradient (deltaP = PG - Pi). DeltaP increased from 38.1 +/- 1.2 in control to 45.9 +/- 1.3 mm Hg after Asn-1, Val-5 AII and essentially neutralized the effect of decreased rpf in sngfr. The sngfr then fell as a result of a decreased in LpA from 0.063 +/- 0.008 in control to 0.028 +/- 0.004 nl/s/g kidney/mm Hg after Asn-1, Val-5 AII (P less than 0.02). Lower doses of Asp-1, Ile-5 AII (less than 3 ng/100 g body wt/min) had no effect on sngfr, rpf, deltaP, and afferent and efferent vascular resistance, but significantly elevated systemic blood pressure, suggesting peripheral effects on smooth muscle at this low dose. LpA was 0.044 +/- 0.007 nl/s/g kidney/mm Hg after low-dose Asp-1, Ile-5 AII, and 0.063 +/- 0.008 in the control group (0.02 greater than P greater than 0.1). Higher, equally pressor doses of native AII (5 ng/100 g body wt/min) produced effects almost identical to similar quantites of synthetic Asn-1, Val-5 AII upon rpf, deltaP, sngfr, and renal vascular resistance. LpA again fell to 0.026 +/- 0.004 nl/s/g kidney/mn Hg, a value almost identical to that after the synthetic AII. Paired studies with Asp-1, Ile-5 AII also demonstrated a consistent reduction in LpA."} {"id": "PMID:1254728", "title": "Effects of brief starvation on muscle amino acid metabolism in nonobese man.", "content": "A reduction in the release of substrate amino acids from skeletal muscle largely explains the decrease in gluconeogenesis characterizing prolonged starvation. Brief starvation is associated with an increase in gluconeogenesis, suggesting increased release of amino acids from muscle. In the present studies, accelerated amino acid release from skeletal muscle induced by brief starvation was sought to account for the accompanying augmentation of gluconeogenesis. To do this amino acid balance across forearm muscles was quantified in 15 postabsorptive (overnight fasted) subjects and in 7 subjects fasted for 60 h. Fasting significantly reduced basal insulin (11.3-7.5 muU/ml) and increased glucagon (116-134 pg/ml). Muscle release of the principal glycogenic amino acids increased. Alanine release increased 59.4%. The increase in release for all amino acids averaged 69.4% and was statistically significant for threonine, serine, glycine, alanine, alpha-aminobutyrate, methionine, tyrosine, and lysine. Thus, with brief starvation, muscle release of glycogenic amino acids increases strikingly. This contrasts with the reduction of amino acid release characterizing prolonged starvation. The adaptation of peripheral tissue metabolism to brief starvation is best explained by the decrease in insulin.", "contents": "Effects of brief starvation on muscle amino acid metabolism in nonobese man. A reduction in the release of substrate amino acids from skeletal muscle largely explains the decrease in gluconeogenesis characterizing prolonged starvation. Brief starvation is associated with an increase in gluconeogenesis, suggesting increased release of amino acids from muscle. In the present studies, accelerated amino acid release from skeletal muscle induced by brief starvation was sought to account for the accompanying augmentation of gluconeogenesis. To do this amino acid balance across forearm muscles was quantified in 15 postabsorptive (overnight fasted) subjects and in 7 subjects fasted for 60 h. Fasting significantly reduced basal insulin (11.3-7.5 muU/ml) and increased glucagon (116-134 pg/ml). Muscle release of the principal glycogenic amino acids increased. Alanine release increased 59.4%. The increase in release for all amino acids averaged 69.4% and was statistically significant for threonine, serine, glycine, alanine, alpha-aminobutyrate, methionine, tyrosine, and lysine. Thus, with brief starvation, muscle release of glycogenic amino acids increases strikingly. This contrasts with the reduction of amino acid release characterizing prolonged starvation. The adaptation of peripheral tissue metabolism to brief starvation is best explained by the decrease in insulin."} {"id": "PMID:1254729", "title": "Rapid diagnosis of anaerobic infections by direct gas-liquid chromatography of clinical speciments.", "content": "Current methods to isolate and identify anaerobic bacteria are laborious and time consuming. It was postulated that the short-chain fatty acids (SCFA) produced by these organisms might serve as microbial markers in clinical material. 98 specimens of pus or serous fluid were analyzed by gas-liquid chromatography, and findings were compared with culture results. Good correlations were found for the recovery of anaerobic Gram-negative bacilli and the presence of isobutyric, butyric, and succinic acids. 19 of 20 specimens with significant amounts of these acids (greater than 0.01 mumol/ml) yielded bacteroides or fusobacteria. Culture of the single \"false-positive\" specimen failed to grow anaerobic Gram-negative bacilli, although clinical data and Gram-stain suggested their presence. 77 of 78 specimens which has insignificant concentrations of the marker acids failed to yield anaerobic, Gram-negative bacilli in culture. The single \"false-negative\" specimen yielded Bacteroides pneumosintes, an organism which does not ferment carbohydrates. It is concluded that direct gas-liquid chromatographic analysis of clinical specimens provides a rapid presumptive test for the presence of anaerobic, Gram-negative bacilli.", "contents": "Rapid diagnosis of anaerobic infections by direct gas-liquid chromatography of clinical speciments. Current methods to isolate and identify anaerobic bacteria are laborious and time consuming. It was postulated that the short-chain fatty acids (SCFA) produced by these organisms might serve as microbial markers in clinical material. 98 specimens of pus or serous fluid were analyzed by gas-liquid chromatography, and findings were compared with culture results. Good correlations were found for the recovery of anaerobic Gram-negative bacilli and the presence of isobutyric, butyric, and succinic acids. 19 of 20 specimens with significant amounts of these acids (greater than 0.01 mumol/ml) yielded bacteroides or fusobacteria. Culture of the single \"false-positive\" specimen failed to grow anaerobic Gram-negative bacilli, although clinical data and Gram-stain suggested their presence. 77 of 78 specimens which has insignificant concentrations of the marker acids failed to yield anaerobic, Gram-negative bacilli in culture. The single \"false-negative\" specimen yielded Bacteroides pneumosintes, an organism which does not ferment carbohydrates. It is concluded that direct gas-liquid chromatographic analysis of clinical specimens provides a rapid presumptive test for the presence of anaerobic, Gram-negative bacilli."} {"id": "PMID:1254730", "title": "The effect of inhibition of prostaglandin synthesis on urinary sodium excretion in the conscious dog.", "content": "Studies were performed to determine the effect of decreased endogenous release of renal prostaglandins on urinary sodium excretion. Two structurally dissimilar inhibitors of prostaglandin synthesis were employed, and studies were performed in conscious dogs allowed to recover from prior surgical instrumentation. Either meclofenamate (2 mg/kg) or the competitive prostaglandin inhibitor RO 20-5720 (1 mg/kg) was given to seven unanesthetized dogs undergoing a water diuresis. The administration of either prostaglandin inhibitor did not alter glomerular filtration rate, renal plasma flow, urinary volume, or potassium excretion. Sodium excretion, however, increased from 32 to 130 mueq/min (P less than 0.02). Essentially, the entire increase in sodium excretion was due to an increase in urinary sodium concentration from 7.7 to 28.3 meq/liter (P less than 0.02). On a different day, the same animals were studied before and after administration of the diluent of the prostaglandin inhibitor. No change was noted in sodium excretion or any other parameter. Thus, these findings suggest that prostaglandin inhibition in the conscious dog is associated with a natriuresis without a change in urinary volume or potassium excretion during water diuresis. This may indicate that the natruiresis was due to diminished sodium reabsorption beyond the distal tubule.", "contents": "The effect of inhibition of prostaglandin synthesis on urinary sodium excretion in the conscious dog. Studies were performed to determine the effect of decreased endogenous release of renal prostaglandins on urinary sodium excretion. Two structurally dissimilar inhibitors of prostaglandin synthesis were employed, and studies were performed in conscious dogs allowed to recover from prior surgical instrumentation. Either meclofenamate (2 mg/kg) or the competitive prostaglandin inhibitor RO 20-5720 (1 mg/kg) was given to seven unanesthetized dogs undergoing a water diuresis. The administration of either prostaglandin inhibitor did not alter glomerular filtration rate, renal plasma flow, urinary volume, or potassium excretion. Sodium excretion, however, increased from 32 to 130 mueq/min (P less than 0.02). Essentially, the entire increase in sodium excretion was due to an increase in urinary sodium concentration from 7.7 to 28.3 meq/liter (P less than 0.02). On a different day, the same animals were studied before and after administration of the diluent of the prostaglandin inhibitor. No change was noted in sodium excretion or any other parameter. Thus, these findings suggest that prostaglandin inhibition in the conscious dog is associated with a natriuresis without a change in urinary volume or potassium excretion during water diuresis. This may indicate that the natruiresis was due to diminished sodium reabsorption beyond the distal tubule."} {"id": "PMID:1254731", "title": "Glucagon response to hypoglycemia in sympathectomized man.", "content": "Hypoglycemia stimulates immunoreactive glucagon (IRG) secretion and increases the activity of the sympathetic nervous system. To ascertain if the augmented alpha cell activity evoked by glucopenia is mediated by the adrenergic nervous system, the glucagon response to insulin-induced hypoglycemia of five subjects with neurologically complete cervical transections resulting from trauma, thereby disrupting their hypothalamic sympathetic outflow, was compared to six healthy volunteers. In addition to clinical neurological evaluation, completeness of sympathectomy was verified by failure to raise plasma norepinephrine levels during hypoglycemia compared to the two- and threefold increase observed in controls. Total IRG response (IRG area above basal 0-90 min) and peak IRG levels achieved were the same in the quadriplegics and the controls. Although the glucagon rise tended to be slower, and the peak levels attained occurred later in the quadriplegic patients than in the controls, this response was appropriate for their sugar decline, which was slower and reached the nadir later than in the control subjects. These observations that the glucagon release during insulin-induced hypoglycemia is normal in subjects whose hypothalamic sympathetic outflow has been interrupted provide strong evidence that the sympathetic nervous system does not mediate the glucagon response to hypoglycemia.", "contents": "Glucagon response to hypoglycemia in sympathectomized man. Hypoglycemia stimulates immunoreactive glucagon (IRG) secretion and increases the activity of the sympathetic nervous system. To ascertain if the augmented alpha cell activity evoked by glucopenia is mediated by the adrenergic nervous system, the glucagon response to insulin-induced hypoglycemia of five subjects with neurologically complete cervical transections resulting from trauma, thereby disrupting their hypothalamic sympathetic outflow, was compared to six healthy volunteers. In addition to clinical neurological evaluation, completeness of sympathectomy was verified by failure to raise plasma norepinephrine levels during hypoglycemia compared to the two- and threefold increase observed in controls. Total IRG response (IRG area above basal 0-90 min) and peak IRG levels achieved were the same in the quadriplegics and the controls. Although the glucagon rise tended to be slower, and the peak levels attained occurred later in the quadriplegic patients than in the controls, this response was appropriate for their sugar decline, which was slower and reached the nadir later than in the control subjects. These observations that the glucagon release during insulin-induced hypoglycemia is normal in subjects whose hypothalamic sympathetic outflow has been interrupted provide strong evidence that the sympathetic nervous system does not mediate the glucagon response to hypoglycemia."} {"id": "PMID:1254732", "title": "Nonsuppressible insulin-like activity of human serum. A potent inhibitor of insulin degradation.", "content": "Nonsuppressible insulin-like activity soluble in acid ethanol (NSILA-s) is a well-characterized peptide derived from human serum which has previously been shown to have insulin-like bioactivity and react with both insulin and NSILA-s receptor sites in liver plasma membranes. In the present study we find that NSILA-s is also a potent competitive inhibitor of the insulin-degrading system of the liver plasma membrane. The most purified NSILA-s preparation tested was 20-fold more potent than insulin itself, and significant inhibition of insulin degradation occurred at concentrations of NSILA-s similar to those found in plasma.", "contents": "Nonsuppressible insulin-like activity of human serum. A potent inhibitor of insulin degradation. Nonsuppressible insulin-like activity soluble in acid ethanol (NSILA-s) is a well-characterized peptide derived from human serum which has previously been shown to have insulin-like bioactivity and react with both insulin and NSILA-s receptor sites in liver plasma membranes. In the present study we find that NSILA-s is also a potent competitive inhibitor of the insulin-degrading system of the liver plasma membrane. The most purified NSILA-s preparation tested was 20-fold more potent than insulin itself, and significant inhibition of insulin degradation occurred at concentrations of NSILA-s similar to those found in plasma."} {"id": "PMID:1254733", "title": "Apoprotein B in fasting and postprandial human jejunal mucosa.", "content": "We tested whether apoprotein B is present in fasting and postprandial human duodenojejunal mucosa because lipoprotein-like particles are visualized by electron microscopy within the smooth endoplasmic reticulum and the Golgi cisternae of these absorptive cells. Duodenojejunal biopsies from normal volunteers were incubated in citrate buffer and were shaken in 1% EDTA so that absorptive cells could be freed from underlying tissue. Apoprotein B was determined by double-antibody radioimmunoassay in homogenates of absorptive cells. The preparations of absorptive cells were shown to be uncontaminated by plasma lipoproteins; they did not contain any albumin by immunodiffusion able to detect 2 mug/ml. They adsorbed less than 0.1% of 125I-low density lipoprotein which was added to the citrate buffer. Cell preparations from suction biopsies of human rectum contained no detectable apoprotein B. Duodenojejunal absorptive cells from 22 fasting subjects contained 3.2 +/- 0.5 mug of apoprotein B per 100 mg (wet wt) of biopsies or 1.3 mug of apoprotein B per mg of total cell protein. The amount of apoprotein B per milligram of cell protein fell to 0.3 mug in 14 of these individuals whose mucosa was also sampled 45 min after instilling fat intraduodenally. These experiments provide immunochemical evidence that human duodenojejunal absorptive cells contain apoprotein B. This technique should be valuable for studying the physiology of intestinal lipoproteins in absorption and in patients with hyperlipidemia.", "contents": "Apoprotein B in fasting and postprandial human jejunal mucosa. We tested whether apoprotein B is present in fasting and postprandial human duodenojejunal mucosa because lipoprotein-like particles are visualized by electron microscopy within the smooth endoplasmic reticulum and the Golgi cisternae of these absorptive cells. Duodenojejunal biopsies from normal volunteers were incubated in citrate buffer and were shaken in 1% EDTA so that absorptive cells could be freed from underlying tissue. Apoprotein B was determined by double-antibody radioimmunoassay in homogenates of absorptive cells. The preparations of absorptive cells were shown to be uncontaminated by plasma lipoproteins; they did not contain any albumin by immunodiffusion able to detect 2 mug/ml. They adsorbed less than 0.1% of 125I-low density lipoprotein which was added to the citrate buffer. Cell preparations from suction biopsies of human rectum contained no detectable apoprotein B. Duodenojejunal absorptive cells from 22 fasting subjects contained 3.2 +/- 0.5 mug of apoprotein B per 100 mg (wet wt) of biopsies or 1.3 mug of apoprotein B per mg of total cell protein. The amount of apoprotein B per milligram of cell protein fell to 0.3 mug in 14 of these individuals whose mucosa was also sampled 45 min after instilling fat intraduodenally. These experiments provide immunochemical evidence that human duodenojejunal absorptive cells contain apoprotein B. This technique should be valuable for studying the physiology of intestinal lipoproteins in absorption and in patients with hyperlipidemia."} {"id": "PMID:1254734", "title": "Metabolic effects of cloprednol-a new systemic corticosteroid.", "content": "The short-term metabolic effects of cloprednol, a new short-acting synthetic corticosteroid, were evaluated in four normal subjects. Cloprednol, 12.5 mg/day, in one subject had no appreciable effect on urinary excretion of sodium, potassium, nitrogen, or calcium. Cloprednol, 20 mg/day, in three subjects had no significant effect on mean daily urinary sodium and potassium excretion, although mild, transient sodium retention and kaliuresis were observed. One subject had increased nitrogen excretion and all three had a small increase in calcium excretion. Prednisolone, 40 mg/day, a dose with antiinflammatory potency equivalent to 20 mg/day cloprednol, given subsequently to two subjects under identical conditions resulted in sodium and potassium excretion results similar to those of cloprednol, 20 mg/day, but produced a much greater increase in nitrogen and calcium excretion. These results suggest that, like prednisolone, cloprednol lacks the sodium-retaining properties of hydrocortisone and raise the possibility that cloprednol has less of a deleterious effect on nitrogen and calcium excretion than prednisolone.", "contents": "Metabolic effects of cloprednol-a new systemic corticosteroid. The short-term metabolic effects of cloprednol, a new short-acting synthetic corticosteroid, were evaluated in four normal subjects. Cloprednol, 12.5 mg/day, in one subject had no appreciable effect on urinary excretion of sodium, potassium, nitrogen, or calcium. Cloprednol, 20 mg/day, in three subjects had no significant effect on mean daily urinary sodium and potassium excretion, although mild, transient sodium retention and kaliuresis were observed. One subject had increased nitrogen excretion and all three had a small increase in calcium excretion. Prednisolone, 40 mg/day, a dose with antiinflammatory potency equivalent to 20 mg/day cloprednol, given subsequently to two subjects under identical conditions resulted in sodium and potassium excretion results similar to those of cloprednol, 20 mg/day, but produced a much greater increase in nitrogen and calcium excretion. These results suggest that, like prednisolone, cloprednol lacks the sodium-retaining properties of hydrocortisone and raise the possibility that cloprednol has less of a deleterious effect on nitrogen and calcium excretion than prednisolone."} {"id": "PMID:1254735", "title": "Pharmacokinetics of 125I-iothalamate and 131I-o-iodohippurate in man.", "content": "The pharmacokinetics of 125I-iothalamate (IOT125I) and 131I-o-iodohippurate (OIH131I) have been studied in patients with varying degrees of renal insufficiency. Both compounds have been shown to obey two-compartment model kinetics after intravenous administration. The clearances are closely related to renal function, but poor correlations were obtained between renal function and compartmental distribution characteristics. This study provides further evidence that IOT125I and OIH131I may be used as indicators of renal function in patients after a single intravenous injection.", "contents": "Pharmacokinetics of 125I-iothalamate and 131I-o-iodohippurate in man. The pharmacokinetics of 125I-iothalamate (IOT125I) and 131I-o-iodohippurate (OIH131I) have been studied in patients with varying degrees of renal insufficiency. Both compounds have been shown to obey two-compartment model kinetics after intravenous administration. The clearances are closely related to renal function, but poor correlations were obtained between renal function and compartmental distribution characteristics. This study provides further evidence that IOT125I and OIH131I may be used as indicators of renal function in patients after a single intravenous injection."} {"id": "PMID:1254873", "title": "Fear of trying.", "content": "Unless the nutrition community intervenes in national and international policymaking, the world could well be headed for serious trouble with deaths from starvation on a consequential scale. There has been near-total dissociation between agricultural planning policies and food distribution and nutritional needs of populations. Unfortunately, the nutrition community is out of the mainstream of forces which affect nutritional status and which produce the macro-decisions. Why? Perhaps the professionals have too narrow a view of their role; although malnutrition is a health problem, the solution is not necessarily one of health delivery. Perhaps they don't seriously wish to be involved with policy change and the work it entails. Perhaps, by being unable to achieve consensus within their own ranks, they have generated a lack of credibility. The nutrition community needs to recognize a broader scope for nutrition and to take new approaches in advocacy directed to education policy-makers. No one else can play this role with authority.", "contents": "Fear of trying. Unless the nutrition community intervenes in national and international policymaking, the world could well be headed for serious trouble with deaths from starvation on a consequential scale. There has been near-total dissociation between agricultural planning policies and food distribution and nutritional needs of populations. Unfortunately, the nutrition community is out of the mainstream of forces which affect nutritional status and which produce the macro-decisions. Why? Perhaps the professionals have too narrow a view of their role; although malnutrition is a health problem, the solution is not necessarily one of health delivery. Perhaps they don't seriously wish to be involved with policy change and the work it entails. Perhaps, by being unable to achieve consensus within their own ranks, they have generated a lack of credibility. The nutrition community needs to recognize a broader scope for nutrition and to take new approaches in advocacy directed to education policy-makers. No one else can play this role with authority."} {"id": "PMID:1254874", "title": "Comments on the division of labor in occupations concerned with food.", "content": "The roles of men and women in relation to food have always been sharply defined: animals belonged to men and plants and food preparation to women. Thus, when the land-grant colleges were established, men were taught animal husbandry and agricultural methods; in home economics, women learned the \"home-making\" arts, including nutrition and were concerned with people. But, as nutrition became more scientific, men took it over, separating it from home economics. In so doing, less attention was paid to the human elements in food production. World food policies are now made without regard to feeding people, and women have been progressively left out in the decision-making. The increase in nutritional knowledge in the last half century has had little effect on policies. Because Americans set the pattern the rest of the world will emulate, we must come to the realization that we cannot alleviate hunger with money alone-hunger is relieved with food, and food supplies are finite. Real sacrifices in terms of food itself, such as were made in World Wars I and II, will be necessary. Knowledge that millions are truly hungry may convince mothers to feed their children and families in different ways.", "contents": "Comments on the division of labor in occupations concerned with food. The roles of men and women in relation to food have always been sharply defined: animals belonged to men and plants and food preparation to women. Thus, when the land-grant colleges were established, men were taught animal husbandry and agricultural methods; in home economics, women learned the \"home-making\" arts, including nutrition and were concerned with people. But, as nutrition became more scientific, men took it over, separating it from home economics. In so doing, less attention was paid to the human elements in food production. World food policies are now made without regard to feeding people, and women have been progressively left out in the decision-making. The increase in nutritional knowledge in the last half century has had little effect on policies. Because Americans set the pattern the rest of the world will emulate, we must come to the realization that we cannot alleviate hunger with money alone-hunger is relieved with food, and food supplies are finite. Real sacrifices in terms of food itself, such as were made in World Wars I and II, will be necessary. Knowledge that millions are truly hungry may convince mothers to feed their children and families in different ways."} {"id": "PMID:1254875", "title": "Progress toward a national food policy-its implications.", "content": "Over the last several years, the Senate Select Committee on Nutrition and Human Needs has conducted hearings in an effort to obtain experts' recommendations, prior to proposing legislation to establish a comprehensive national nutrition plan. The framework for such a plan, as developed by the Committee, is presented here. A \"nutritional state of the union\" report-to include a formal assessment of existing conditions plus specific goals-would be made annually. To insure accountability, a Federal Nutrition Office, headed by a Cabinet-level official, would be responsible for coordination and monitoring all nutrition programs in all governmental agencies and would have the right to review (but not veto) proposals before an agency could issue them officially. In addition, there would be a National Nutrition Center in the Department of Health, Education, and Welfare, charged with day-to-day administration of expanded nutrition program. This Center would operate at the Sub-Cabinet level.", "contents": "Progress toward a national food policy-its implications. Over the last several years, the Senate Select Committee on Nutrition and Human Needs has conducted hearings in an effort to obtain experts' recommendations, prior to proposing legislation to establish a comprehensive national nutrition plan. The framework for such a plan, as developed by the Committee, is presented here. A \"nutritional state of the union\" report-to include a formal assessment of existing conditions plus specific goals-would be made annually. To insure accountability, a Federal Nutrition Office, headed by a Cabinet-level official, would be responsible for coordination and monitoring all nutrition programs in all governmental agencies and would have the right to review (but not veto) proposals before an agency could issue them officially. In addition, there would be a National Nutrition Center in the Department of Health, Education, and Welfare, charged with day-to-day administration of expanded nutrition program. This Center would operate at the Sub-Cabinet level."} {"id": "PMID:1254876", "title": "Out-patient dietary management in the Prader-Willi syndrome.", "content": "Dietary adherence of eight children with the Prader-Willi syndrome was studied in the home environment. Weight changes were recorded at two-week intervals, and measured two-week dietary records were completed twice during the study by the parents of seven of the children. An eighth child was similarly followed for three months, and one dietary record was obtained. Calories, protein, fat, and carbohydrate contents were calculated, and related to recorded weight changes to determine which diets were most practical in controlling weight gain. Caloric requirements of children with the Prader-Willi syndrome appear to be much lower than those of healthy, active children of comparable ages. Age, degree of obesity, familial relationships, and probably, composition of the diet influenced the effectiveness of a given diet. Each family designed a diet which took into consideration the family's eating habits, as well as the needs of the Prader-Willi child. Frequent contact with the dietitian enabled each family to try new food preparation ideas. The effectiveness and acceptability of a low caloric, very low-carbohydrate diet should be tested over long periods in Prader-Willi children whose obesity is being managed in a non-institution setting.", "contents": "Out-patient dietary management in the Prader-Willi syndrome. Dietary adherence of eight children with the Prader-Willi syndrome was studied in the home environment. Weight changes were recorded at two-week intervals, and measured two-week dietary records were completed twice during the study by the parents of seven of the children. An eighth child was similarly followed for three months, and one dietary record was obtained. Calories, protein, fat, and carbohydrate contents were calculated, and related to recorded weight changes to determine which diets were most practical in controlling weight gain. Caloric requirements of children with the Prader-Willi syndrome appear to be much lower than those of healthy, active children of comparable ages. Age, degree of obesity, familial relationships, and probably, composition of the diet influenced the effectiveness of a given diet. Each family designed a diet which took into consideration the family's eating habits, as well as the needs of the Prader-Willi child. Frequent contact with the dietitian enabled each family to try new food preparation ideas. The effectiveness and acceptability of a low caloric, very low-carbohydrate diet should be tested over long periods in Prader-Willi children whose obesity is being managed in a non-institution setting."} {"id": "PMID:1254877", "title": "Comprehensive evaluation of fatty acids in foods. VI. Cereal products.", "content": "Information on total lipid and fatty acid composition or cereal grains and their products used for food has been collated in a comprehensive search of world literature published since 1960. Data considered most suitable for use for representing contents of total lipids and fatty acids have been tabulated and are presented. In developing these data, attention was given to stability and other chemical properties of the lipids, lipid composition of the different parts of the grain, and to such factors as genetics, production, processing, and analytical methods used in extracting and determining the fat and fatty acids in cereal products.", "contents": "Comprehensive evaluation of fatty acids in foods. VI. Cereal products. Information on total lipid and fatty acid composition or cereal grains and their products used for food has been collated in a comprehensive search of world literature published since 1960. Data considered most suitable for use for representing contents of total lipids and fatty acids have been tabulated and are presented. In developing these data, attention was given to stability and other chemical properties of the lipids, lipid composition of the different parts of the grain, and to such factors as genetics, production, processing, and analytical methods used in extracting and determining the fat and fatty acids in cereal products."} {"id": "PMID:1254878", "title": "Folklore and food habits.", "content": "The folklore surrounding food habits developed from uncertainty and fear in mankind's quest for food. In an attempt to gain control of his destiny, man developed various magical practices which would perhaps assure an abundance of food. The practice and beliefs did not develop haphazardly, but, on examination, reveal a type of \"folk logic\" explained by Sir James Frazer's concepts of contagious and homeopathic magic. The \"logic\" was extended to specific practices in preparing foods, eating of foods on special days, the use of food in curing certain diseases, and forbidding foods at certain times. The folk were attempting to coordinate the phenomena of their world according to cause and effect much the same as modern Americans coordinate their world. However, the basic assuptions were different.", "contents": "Folklore and food habits. The folklore surrounding food habits developed from uncertainty and fear in mankind's quest for food. In an attempt to gain control of his destiny, man developed various magical practices which would perhaps assure an abundance of food. The practice and beliefs did not develop haphazardly, but, on examination, reveal a type of \"folk logic\" explained by Sir James Frazer's concepts of contagious and homeopathic magic. The \"logic\" was extended to specific practices in preparing foods, eating of foods on special days, the use of food in curing certain diseases, and forbidding foods at certain times. The folk were attempting to coordinate the phenomena of their world according to cause and effect much the same as modern Americans coordinate their world. However, the basic assuptions were different."} {"id": "PMID:1254879", "title": "Hypochondriasis and the elderly.", "content": "Hypochondriasis is poorly understood and poorly treated. Attempts to classify it have been unsatisfactory except for Pilowsky's division into primary and secondary groups. Twenty consecutive cases of hypochondriasis in elderly patients were studied; 4 were of the primary type and 16 of the secondary type. For the primary group, neither family therapy nor hospitalization was needed, and the prognosis was good. In contrast, hospitalization was always advised for the secondary group, and such patients improved while in the hospital. Psychotropic drugs, a therapeutic milieu, and often electroshock therapy were needed to treat depression. After discharge, successful treatment necessitated Day Care programs and the long-term use of family therapy. Treatment was unsuccessful in 8 patients characterized by refusal to become involved in post-discharge Day Care programs and family therapy.", "contents": "Hypochondriasis and the elderly. Hypochondriasis is poorly understood and poorly treated. Attempts to classify it have been unsatisfactory except for Pilowsky's division into primary and secondary groups. Twenty consecutive cases of hypochondriasis in elderly patients were studied; 4 were of the primary type and 16 of the secondary type. For the primary group, neither family therapy nor hospitalization was needed, and the prognosis was good. In contrast, hospitalization was always advised for the secondary group, and such patients improved while in the hospital. Psychotropic drugs, a therapeutic milieu, and often electroshock therapy were needed to treat depression. After discharge, successful treatment necessitated Day Care programs and the long-term use of family therapy. Treatment was unsuccessful in 8 patients characterized by refusal to become involved in post-discharge Day Care programs and family therapy."} {"id": "PMID:1254880", "title": "Estrogen-androgen levels in aging men and women: therapeutic considerations.", "content": "The influence of aging on serum levels of gonadotropins (FSH and LH), testosterone and estradiol was studied in the following groups: 4 normal men (ages 30 to 50), 38 men with symptoms of the male climacteric (ages 51 to 84), 25 men with relative impotence (ages 31 to 50), 10 normal women (ages 24 to 31), and 6 menopausal women (ages 58 to 76). FSH and LH levels began to rise in men in their 40's, and the increase became more conspicuous in the later age decades. The degree of elevation was nowhere comparable to that observed in the aging women. In the male, the serum testosterone levels showed a progressive decrease from the fifth age decade onward, whereas in the female there was an increase after the menopause. Estradiol levels showed no significant change in the aged male, but they were somewhat higher than in the aged female. Exceptions to the low-testosterone and low-gonadotropin relationship were observed in individual cases and might be explained by relatively high estradiol values. Proper replacement therapy by means of estrogens for the postmenopausal female and androgens for the aging male is often of great benefit, physically and emotionally.", "contents": "Estrogen-androgen levels in aging men and women: therapeutic considerations. The influence of aging on serum levels of gonadotropins (FSH and LH), testosterone and estradiol was studied in the following groups: 4 normal men (ages 30 to 50), 38 men with symptoms of the male climacteric (ages 51 to 84), 25 men with relative impotence (ages 31 to 50), 10 normal women (ages 24 to 31), and 6 menopausal women (ages 58 to 76). FSH and LH levels began to rise in men in their 40's, and the increase became more conspicuous in the later age decades. The degree of elevation was nowhere comparable to that observed in the aging women. In the male, the serum testosterone levels showed a progressive decrease from the fifth age decade onward, whereas in the female there was an increase after the menopause. Estradiol levels showed no significant change in the aged male, but they were somewhat higher than in the aged female. Exceptions to the low-testosterone and low-gonadotropin relationship were observed in individual cases and might be explained by relatively high estradiol values. Proper replacement therapy by means of estrogens for the postmenopausal female and androgens for the aging male is often of great benefit, physically and emotionally."} {"id": "PMID:1254881", "title": "Treatable aspects of the dementia syndrome.", "content": "With attentive medical management, the elderly demented patient can live in greater comfort, dignity and independence. Errors in supervision can result in a drug intoxication, misdiagnoses, and personal neglect. Many of the elderly have a chronic dementing illness, and disability often is accelerated by complications. However, some of these complications are treatable. Case histories are presented to illustrate pitfalls in the care of such patients.", "contents": "Treatable aspects of the dementia syndrome. With attentive medical management, the elderly demented patient can live in greater comfort, dignity and independence. Errors in supervision can result in a drug intoxication, misdiagnoses, and personal neglect. Many of the elderly have a chronic dementing illness, and disability often is accelerated by complications. However, some of these complications are treatable. Case histories are presented to illustrate pitfalls in the care of such patients."} {"id": "PMID:1254882", "title": "Cardiovascular effects of levodopa in aged versus younger patients with Parkinson's disease.", "content": "The cardiovascular effects of prolonged administration of levodopa were studied in 54 men and women with Parkinson's disease; 23 of them were younger than 70 and 31 were 70 or older. The patients were evaluated clinically before treatment was started and at regular intervals thereafter. The average optimal dosage of levodopa for both age groups was 3.0 and 2.5 gm per day, respectively, during an average treatment period of 20.7 months. Eleven patients showed hypotension (systolic BP of 105 mm Hg or less) that was not related to dosage; in only 6 did the drug have to be permanently discontinued because of syncope; 3 of this group had an associated psychiatric disorder. Four patients had pretreatment hypertension; in 3 the BP fell to normal during therapy; in the remaining patient the hypertension persisted and was successfully treated by an antihypertensive drug. In 5 patients an occasional atrial or ventricular ectopic beat was noted both before and during levodopa therapy but no therapeutic intervention was required. Thirty of the 46 patients with adequate ECG follow-up did not show any significant changes; 5 others showed an increase, and 11 a decrease in myocardial ischemia. Thus the administration of levodopa in elderly patients with or without heart disease is a relatively safe procedure. The only exception would be patients over 70 years of age with a history of previous myocardial infarction. In this group there seems to be a higher incidence of clinically significant hypotension. In such patients, levodopa therapy should be carried out with great caution.", "contents": "Cardiovascular effects of levodopa in aged versus younger patients with Parkinson's disease. The cardiovascular effects of prolonged administration of levodopa were studied in 54 men and women with Parkinson's disease; 23 of them were younger than 70 and 31 were 70 or older. The patients were evaluated clinically before treatment was started and at regular intervals thereafter. The average optimal dosage of levodopa for both age groups was 3.0 and 2.5 gm per day, respectively, during an average treatment period of 20.7 months. Eleven patients showed hypotension (systolic BP of 105 mm Hg or less) that was not related to dosage; in only 6 did the drug have to be permanently discontinued because of syncope; 3 of this group had an associated psychiatric disorder. Four patients had pretreatment hypertension; in 3 the BP fell to normal during therapy; in the remaining patient the hypertension persisted and was successfully treated by an antihypertensive drug. In 5 patients an occasional atrial or ventricular ectopic beat was noted both before and during levodopa therapy but no therapeutic intervention was required. Thirty of the 46 patients with adequate ECG follow-up did not show any significant changes; 5 others showed an increase, and 11 a decrease in myocardial ischemia. Thus the administration of levodopa in elderly patients with or without heart disease is a relatively safe procedure. The only exception would be patients over 70 years of age with a history of previous myocardial infarction. In this group there seems to be a higher incidence of clinically significant hypotension. In such patients, levodopa therapy should be carried out with great caution."} {"id": "PMID:1254883", "title": "Miles' resection for cancer of the rectum.", "content": "Miles' resection is the optimal surgical operation for cancer involving the lowermost third of the rectum, although some surgeons question the wisdom of subjecting the patient to permanent colostomy and use fulguration as the alternative. In the author's series of 100 patients, the five-year survival rate was 41.6%. The operative mortality rate was 4%. The median distance of the cancer above the dentate line was 3 cm and the average distance was 4.6 cm. Fifty patients had Dukes' C lesions. Of the 100 patients, 95 had adenocarcinoma, 3 had squamous-cell carcinoma, 1 had a cloacogenic lesion, and 1 had melanocarcinoma. Complications were surprisingly few. Eleven patients had perineal recurrence. The relatively poor survival rate is attributed to anatomic limitations for radical surgical measures and to the spread of cancer cells by the time of operation. Regular check-up examinations are most effective in the prevention of rectal cancer.", "contents": "Miles' resection for cancer of the rectum. Miles' resection is the optimal surgical operation for cancer involving the lowermost third of the rectum, although some surgeons question the wisdom of subjecting the patient to permanent colostomy and use fulguration as the alternative. In the author's series of 100 patients, the five-year survival rate was 41.6%. The operative mortality rate was 4%. The median distance of the cancer above the dentate line was 3 cm and the average distance was 4.6 cm. Fifty patients had Dukes' C lesions. Of the 100 patients, 95 had adenocarcinoma, 3 had squamous-cell carcinoma, 1 had a cloacogenic lesion, and 1 had melanocarcinoma. Complications were surprisingly few. Eleven patients had perineal recurrence. The relatively poor survival rate is attributed to anatomic limitations for radical surgical measures and to the spread of cancer cells by the time of operation. Regular check-up examinations are most effective in the prevention of rectal cancer."} {"id": "PMID:1254907", "title": "An automated microscope for cytologic research a preliminary evaluation.", "content": "A research-oriented system for automated microscopy is described from an operational point of view. The system consists of a microscope, a TV camera, an automatic cell finder and a servo-driven computer controlled stage. The system is interfaced to a NOVA 840 computer having 112,000 words of 16-bit core memory and extensive peripherals. It is capable of performing a wide variety of image processing tasks and is being used to study various aspects of automated microscopy, with applications in, but not limited to, cytology. Results of preliminary performance evaluations are given.", "contents": "An automated microscope for cytologic research a preliminary evaluation. A research-oriented system for automated microscopy is described from an operational point of view. The system consists of a microscope, a TV camera, an automatic cell finder and a servo-driven computer controlled stage. The system is interfaced to a NOVA 840 computer having 112,000 words of 16-bit core memory and extensive peripherals. It is capable of performing a wide variety of image processing tasks and is being used to study various aspects of automated microscopy, with applications in, but not limited to, cytology. Results of preliminary performance evaluations are given."} {"id": "PMID:1254908", "title": "The use of a slide spinner in the analysis of cell dispersion.", "content": "A simple and reliable method of determining the degree of dispersion of a cell suspension has been developed using the Perkin-Elmer Uni-Smear Spinner. Optimum conditions regarding rate and duration of spin, etc., were first ascertained using dispersed cell cultures including human cervical cancer cells as well as gynecologic samples. After spinning, single cells in suspension appeared as isolated cells on the slides. Cell aggregates, on the other hand, remained together. Therefore, the distribution of cells in various sized aggregates could be easily quantitated and the slides retained for future review. This method was used to evaluate the dispersing effects of trypsin, ethylenediaminetetraacetate and and syringing human on human gynecology samples obtained by routine cervical scrapes. None of the dispersion methods has, so far, produced an adequate monodispersed cell suspension without unacceptable cell loss.", "contents": "The use of a slide spinner in the analysis of cell dispersion. A simple and reliable method of determining the degree of dispersion of a cell suspension has been developed using the Perkin-Elmer Uni-Smear Spinner. Optimum conditions regarding rate and duration of spin, etc., were first ascertained using dispersed cell cultures including human cervical cancer cells as well as gynecologic samples. After spinning, single cells in suspension appeared as isolated cells on the slides. Cell aggregates, on the other hand, remained together. Therefore, the distribution of cells in various sized aggregates could be easily quantitated and the slides retained for future review. This method was used to evaluate the dispersing effects of trypsin, ethylenediaminetetraacetate and and syringing human on human gynecology samples obtained by routine cervical scrapes. None of the dispersion methods has, so far, produced an adequate monodispersed cell suspension without unacceptable cell loss."} {"id": "PMID:1254909", "title": "A real time TV to computer image input system using run coding.", "content": "Run coding applied to the digitized video signal from a TV scan of cell preparations can effect a substantial reduction in the total amount of data, sufficient to permit a moderate size of store to be loaded within one frame time with a representation of the field adequate for computer analysis. This paper describes the design of a run coding interface between a TV scanner and a computer store which also allows control of scan domain, spatial resolution and density resolution. Results are presented showing its efficiency when dealing with cervical smear preparations.", "contents": "A real time TV to computer image input system using run coding. Run coding applied to the digitized video signal from a TV scan of cell preparations can effect a substantial reduction in the total amount of data, sufficient to permit a moderate size of store to be loaded within one frame time with a representation of the field adequate for computer analysis. This paper describes the design of a run coding interface between a TV scanner and a computer store which also allows control of scan domain, spatial resolution and density resolution. Results are presented showing its efficiency when dealing with cervical smear preparations."} {"id": "PMID:1254910", "title": "Coherent optical processing of cervical cytologic samples.", "content": "Earlier research using a very limited data base gave encouraging results for the automated screening of exfoliated cytologic samples using coherent optical processing techniques to examine individual isolated cells. A more thorough investigation involving a larger data base has confirmed our initial results. This investigation was performed using a specially designed Fourier spectrum analyzer and a solid state optical detector array. An analysis was made to determine the performance of a screening system using such a cell-by-cell discriminating device. This analysis indicated that less than 20,000 cells would have to be examined to obtain a system performance level of 1% false negative and 10% false positive error rates with a 1% probability of occurrence of malignant cells in a malignant sample. This performance figure was inferred from measured statistical performance characteristics of a laboratory cell-by-cell screening device using optically generated Fourier transfrom techniques for cell discrimination. The performance of the system was shown to be much more sensitive to cell-by-cell false error rates than false negative error rates. It was also found that the majority of false positive errors were due to misclassifying parabasal cells as malignant. By eliminating parabasal cells, which comprised more than 25% of our normal cell data base, the number of cells needed to be screened dropped by an order of magnitude. It was also shown that there is an inverse quadratic relationship between the percentage of malignant cells in a malignant sample and the number of cells that must be screened to achieve any desired system performance.", "contents": "Coherent optical processing of cervical cytologic samples. Earlier research using a very limited data base gave encouraging results for the automated screening of exfoliated cytologic samples using coherent optical processing techniques to examine individual isolated cells. A more thorough investigation involving a larger data base has confirmed our initial results. This investigation was performed using a specially designed Fourier spectrum analyzer and a solid state optical detector array. An analysis was made to determine the performance of a screening system using such a cell-by-cell discriminating device. This analysis indicated that less than 20,000 cells would have to be examined to obtain a system performance level of 1% false negative and 10% false positive error rates with a 1% probability of occurrence of malignant cells in a malignant sample. This performance figure was inferred from measured statistical performance characteristics of a laboratory cell-by-cell screening device using optically generated Fourier transfrom techniques for cell discrimination. The performance of the system was shown to be much more sensitive to cell-by-cell false error rates than false negative error rates. It was also found that the majority of false positive errors were due to misclassifying parabasal cells as malignant. By eliminating parabasal cells, which comprised more than 25% of our normal cell data base, the number of cells needed to be screened dropped by an order of magnitude. It was also shown that there is an inverse quadratic relationship between the percentage of malignant cells in a malignant sample and the number of cells that must be screened to achieve any desired system performance."} {"id": "PMID:1254911", "title": "Methods of quantitative autoradiography using incident light microphotometry.", "content": "Several different approaches of automated grain counting of microautoradiographic grain densities have been reported in the literature. Application of grain counters to cell biology is limited, however, primarily due to shortage of methods allowing the interpretation of grain counts on a molecular basis. Two suitable methods of quantitative autoradiography at the cellular level are reviewed, developed for the isotopes 14C and 125 I. They permit evaluation of absolute radioactivity in autoradiographs and, thus, determination of synthesis processes such as deoxyribonucleic acid synthesis, and of antigen densities on cell surfaces. In this approach towards quantitative autoradiography, grain densities are compared photometrically over labeled cells and over a standard source on the same autoradiograph. Allowance has to be made for the specific geometric factors of the isotope used. This can be advantageously done with an integrating type of measurement using incident light bright-field. With this type of recording, there is an exponential dependence of the photometric values on the radioactive dose. As an example of application, results are presented of the deoxyribonucleic acid synthesis rate of human myelocytes in aplastic anemia and of the immunoglobulin G density on lymphocyte membranes in the normal state and in chronic lymphocytic leukemia.", "contents": "Methods of quantitative autoradiography using incident light microphotometry. Several different approaches of automated grain counting of microautoradiographic grain densities have been reported in the literature. Application of grain counters to cell biology is limited, however, primarily due to shortage of methods allowing the interpretation of grain counts on a molecular basis. Two suitable methods of quantitative autoradiography at the cellular level are reviewed, developed for the isotopes 14C and 125 I. They permit evaluation of absolute radioactivity in autoradiographs and, thus, determination of synthesis processes such as deoxyribonucleic acid synthesis, and of antigen densities on cell surfaces. In this approach towards quantitative autoradiography, grain densities are compared photometrically over labeled cells and over a standard source on the same autoradiograph. Allowance has to be made for the specific geometric factors of the isotope used. This can be advantageously done with an integrating type of measurement using incident light bright-field. With this type of recording, there is an exponential dependence of the photometric values on the radioactive dose. As an example of application, results are presented of the deoxyribonucleic acid synthesis rate of human myelocytes in aplastic anemia and of the immunoglobulin G density on lymphocyte membranes in the normal state and in chronic lymphocytic leukemia."} {"id": "PMID:1254912", "title": "The hybrid resolution approach to automated autoradiographic analysis.", "content": "The use of radioactive isotopes in the investigation of cells and their relations to an organism as a physiologic unit is an important area of research to the biologist. The manual analysis of the autoradiographs which result from the use of radioactive tracers is, however, very time consuming and prone to error. This paper describes the utilization of hybrid resolution image processing techniques for the rapid and automatic analysis of tissue region autoradiographs. Nine regional features can be extracted and six properties characterized using the present system implementation. Priliminary measurements on two tissue types show good agreement between manual and automated readings.", "contents": "The hybrid resolution approach to automated autoradiographic analysis. The use of radioactive isotopes in the investigation of cells and their relations to an organism as a physiologic unit is an important area of research to the biologist. The manual analysis of the autoradiographs which result from the use of radioactive tracers is, however, very time consuming and prone to error. This paper describes the utilization of hybrid resolution image processing techniques for the rapid and automatic analysis of tissue region autoradiographs. Nine regional features can be extracted and six properties characterized using the present system implementation. Priliminary measurements on two tissue types show good agreement between manual and automated readings."} {"id": "PMID:1254914", "title": "A technique for multiple-cell chromosome karyotyping.", "content": "A new approach to a system for chromosome karyotyping is presented. The system assembles the information about chromosomes from several cells at a time, thereby filtering out noise due to variations in the slide preparations. The system makes i possible to use metaphase spreads which are incomplete due to missing chromosomes, touching and overlapping chromosomes and stain particles. The system gives a precise description of the chromosome complement in terms of distribution function parameters, with the uncertainty of the parameters specificed. The system is adaptive with respect to the initial reference parameter set so that both recognition of normal chromosomes, in spite of the variation displayed among individuals, and identification of aberrant chromosomes are possible. The precise chromosome descriptors can be used to detect differences between the tested individual and various references, in order to find chromosomal abnormalities.", "contents": "A technique for multiple-cell chromosome karyotyping. A new approach to a system for chromosome karyotyping is presented. The system assembles the information about chromosomes from several cells at a time, thereby filtering out noise due to variations in the slide preparations. The system makes i possible to use metaphase spreads which are incomplete due to missing chromosomes, touching and overlapping chromosomes and stain particles. The system gives a precise description of the chromosome complement in terms of distribution function parameters, with the uncertainty of the parameters specificed. The system is adaptive with respect to the initial reference parameter set so that both recognition of normal chromosomes, in spite of the variation displayed among individuals, and identification of aberrant chromosomes are possible. The precise chromosome descriptors can be used to detect differences between the tested individual and various references, in order to find chromosomal abnormalities."} {"id": "PMID:1254915", "title": "Automatic detection and localization of sister chromatid exchanges.", "content": "Sister chromatids of human metaphase chromsomes from cells which have replicated twice in medium containing 5-bromodeoxyuridine exhibit unequal fluorescence when stained with the dye 33258 Hoechst. Sister chromatid exchanges occurring in these chromosomes are apparent as interchanges of brightly and dully fluorescing chromatids. A technique for detecting such exchanges by computer analysis of chromsome images has been developed and found to campare favorably with manual methods. The exchanges have been localized in the context of quinacrine banding patterns.", "contents": "Automatic detection and localization of sister chromatid exchanges. Sister chromatids of human metaphase chromsomes from cells which have replicated twice in medium containing 5-bromodeoxyuridine exhibit unequal fluorescence when stained with the dye 33258 Hoechst. Sister chromatid exchanges occurring in these chromosomes are apparent as interchanges of brightly and dully fluorescing chromatids. A technique for detecting such exchanges by computer analysis of chromsome images has been developed and found to campare favorably with manual methods. The exchanges have been localized in the context of quinacrine banding patterns."} {"id": "PMID:1254916", "title": "Image processing for automated erythrocyte classification.", "content": "Digital image processing and pattern recognition techniques were applied to determine the feasibility of a natural n-space subgrouping of normal and abnormal peripheral blood erythrocytes into well separated categories. The data consisted of 325 digitized red cells from 11 different cell classes. The analysis resulted in five features: (a) size, (b) roundness, (c) spicularity, (d) eccentricity and (e) central gray level distribution. These features separated the data into six distinct condensed subgroups of red cells. Each subgroup consisted of morphologically similar cells: (a) macrocytes, (b) normocytes, (c) schistocytes, acanthocytes and burr cells, (d) microcytes and spherocytes, (e) elliptocytes, sickle cells and pencil forms and (f) target cells. The concept of a quantitative \"red cell differential\" was introduced, utilizing these subgroup definitions to establish subpopulations of red cells, with quantifiable indices for the diagnosis of anemia, at the specimen level.", "contents": "Image processing for automated erythrocyte classification. Digital image processing and pattern recognition techniques were applied to determine the feasibility of a natural n-space subgrouping of normal and abnormal peripheral blood erythrocytes into well separated categories. The data consisted of 325 digitized red cells from 11 different cell classes. The analysis resulted in five features: (a) size, (b) roundness, (c) spicularity, (d) eccentricity and (e) central gray level distribution. These features separated the data into six distinct condensed subgroups of red cells. Each subgroup consisted of morphologically similar cells: (a) macrocytes, (b) normocytes, (c) schistocytes, acanthocytes and burr cells, (d) microcytes and spherocytes, (e) elliptocytes, sickle cells and pencil forms and (f) target cells. The concept of a quantitative \"red cell differential\" was introduced, utilizing these subgroup definitions to establish subpopulations of red cells, with quantifiable indices for the diagnosis of anemia, at the specimen level."} {"id": "PMID:1254917", "title": "Performance of the LARC classifier in clinical laboratories.", "content": "As part of the installation procedure of the LARC leukocyte differential classifier in a clinical laboratory, a 100-slide protocol is carried out to establish the performance of the classifier in the laboratory. The detailed make-up of this protocol and its relationship to key performance parameters for the leukocyte differential are described in detail. Data from the first ten of these protocols are presented which establish the (a) normal ranges, (b) reproducibility, (c) accuracy, (d) false-positive/false-negative rates for the detection of left shifts and (e) false-positive/false-negative rates for the detection of bloods with abnormal cells.", "contents": "Performance of the LARC classifier in clinical laboratories. As part of the installation procedure of the LARC leukocyte differential classifier in a clinical laboratory, a 100-slide protocol is carried out to establish the performance of the classifier in the laboratory. The detailed make-up of this protocol and its relationship to key performance parameters for the leukocyte differential are described in detail. Data from the first ten of these protocols are presented which establish the (a) normal ranges, (b) reproducibility, (c) accuracy, (d) false-positive/false-negative rates for the detection of left shifts and (e) false-positive/false-negative rates for the detection of bloods with abnormal cells."} {"id": "PMID:1254918", "title": "Basic principles of electrical sizing of cells and particles and their realization in the new instrument \"Metricell\".", "content": "To understand the basic events during the passage of particles through the Coulter orifice, three experiments were performed. (1) The denpendence of the volume results on the particle path has been shown by ink-colored particle beams. (2) The deformation and alignment of cells during their passage through the orifice have been photographed by a nano-second photographing technique. (3) The absolute volume evaluation of particles has been studied with model particles in enlarged model orifices of different lengths. A new compact sizing instrument, \"Metricell,\" equipped with a particle-independent electrical calibrating system, is described.", "contents": "Basic principles of electrical sizing of cells and particles and their realization in the new instrument \"Metricell\". To understand the basic events during the passage of particles through the Coulter orifice, three experiments were performed. (1) The denpendence of the volume results on the particle path has been shown by ink-colored particle beams. (2) The deformation and alignment of cells during their passage through the orifice have been photographed by a nano-second photographing technique. (3) The absolute volume evaluation of particles has been studied with model particles in enlarged model orifices of different lengths. A new compact sizing instrument, \"Metricell,\" equipped with a particle-independent electrical calibrating system, is described."} {"id": "PMID:1254919", "title": "The computer analysis of volume distribution curves. Demonstration of two erythrocyte populations of different size in the young guinea pig and analysis of the mechanism of immune lysis of cells by antibody and complement.", "content": "Guinea pig, rat and sheep erythrocytes were sized electrically using the hydrodynamic focusing technique. The experimental curves were approximated with a computer by linear and logarithmic normal distributions. Rat and guinea pig erythrocytes from adult animals were best approximated by one linear normal distribution. Two populations (I, II) of erythrocytes with different mean volume could be demonstrated in young guinea pigs by this analysis. Population I erythrocytes are small, have a lower electrophoretic mobility and are mainly present at birth. They are gradually replaced by the larger population II erythrocytes. Both types of erythrocytes are probably the result of separate differentiation pathways. The analysis of erythrocyte volume distribution curves during immune lysis by antibody and complement shows that intact and ghost erythrocytes are measured by electrical sizing. No volume changes were observed up to the EAC1-8 intermediate. After the addition of C9, a C9 dose-dependent part of the erythrocytes swell permanently to spheroids. The spheroid transformation is a temperature-dependent, all or nothing reaction which is independent of protein osmotic forces from the interior of the cell.", "contents": "The computer analysis of volume distribution curves. Demonstration of two erythrocyte populations of different size in the young guinea pig and analysis of the mechanism of immune lysis of cells by antibody and complement. Guinea pig, rat and sheep erythrocytes were sized electrically using the hydrodynamic focusing technique. The experimental curves were approximated with a computer by linear and logarithmic normal distributions. Rat and guinea pig erythrocytes from adult animals were best approximated by one linear normal distribution. Two populations (I, II) of erythrocytes with different mean volume could be demonstrated in young guinea pigs by this analysis. Population I erythrocytes are small, have a lower electrophoretic mobility and are mainly present at birth. They are gradually replaced by the larger population II erythrocytes. Both types of erythrocytes are probably the result of separate differentiation pathways. The analysis of erythrocyte volume distribution curves during immune lysis by antibody and complement shows that intact and ghost erythrocytes are measured by electrical sizing. No volume changes were observed up to the EAC1-8 intermediate. After the addition of C9, a C9 dose-dependent part of the erythrocytes swell permanently to spheroids. The spheroid transformation is a temperature-dependent, all or nothing reaction which is independent of protein osmotic forces from the interior of the cell."} {"id": "PMID:1254920", "title": "Comparison of techniques improving the resolution of standard Coulter cell sizing systems.", "content": "Latex spheres with nominal diameters of 1.857, 2.02, 3.5, 5.2 and 9.69 mum were used to compare improvement in Coulter resolution gained (a) by a simple hydrodynamic focusing modification and (b) by Coulter edit and high resolution circuits. Since pulse size profiles of focused 9.69-mum spheres appeared quasimonodisperse [geometric SD (GSD) congruent to 0.016 congruent to (1 + Arithmetic SD/arithmetic mean)], unfocused profiles of these particles approximated the error function resulting from inhomogeneities in the electric and hydrodynamic sensing-zone fields. As expected, this field error function differed systematically with differences in orifice diameters (30, 50, 70 and 100 mum) and length to diameter ratios (0.75 or 1.2), the error being reduced slightly by the edit circuit and considerably by the high resolution circuit. Data on the 1.857- and 2.02-mum spheres (focused GSDs congruent to 1.06) and 3.5- and 5.2-mum spheres (focused GSDs congruent to 1.6) indicated that the field error affected closely similar particles similarly but its influence on the unfocused population means and variances differed in the GSD regions of 1.06 and 1.60.", "contents": "Comparison of techniques improving the resolution of standard Coulter cell sizing systems. Latex spheres with nominal diameters of 1.857, 2.02, 3.5, 5.2 and 9.69 mum were used to compare improvement in Coulter resolution gained (a) by a simple hydrodynamic focusing modification and (b) by Coulter edit and high resolution circuits. Since pulse size profiles of focused 9.69-mum spheres appeared quasimonodisperse [geometric SD (GSD) congruent to 0.016 congruent to (1 + Arithmetic SD/arithmetic mean)], unfocused profiles of these particles approximated the error function resulting from inhomogeneities in the electric and hydrodynamic sensing-zone fields. As expected, this field error function differed systematically with differences in orifice diameters (30, 50, 70 and 100 mum) and length to diameter ratios (0.75 or 1.2), the error being reduced slightly by the edit circuit and considerably by the high resolution circuit. Data on the 1.857- and 2.02-mum spheres (focused GSDs congruent to 1.06) and 3.5- and 5.2-mum spheres (focused GSDs congruent to 1.6) indicated that the field error affected closely similar particles similarly but its influence on the unfocused population means and variances differed in the GSD regions of 1.06 and 1.60."} {"id": "PMID:1254921", "title": "Estimation of cell size from pulse shape in flow cytofluorometry.", "content": "The fluorescence pulse widths (pulse duration) generated by fluorochromed cells in a flow-through cytofluorometer provide useful information regarding cell (or nuclear) size and possibly other morphologic features. Simple fixed thresholds just above background noise can be used to identify these pulses, but measurements are then strongly affected by random noise and will vary as a result of both pulse amplitude and pulse shape. In this paper, we propose two alternative, amplitude-independent estimates of pulse width. The first is based on a threshold at some fraction of pulse height, or on a pair of thresholds scaled to some fixed central fraction of the total integrated intensity. The second is based on the ratio of pulse area to peak height. The quantitative properties of these width estimators is studied with simulated fluorescence pulses and with experimental specimens of fluorchromed polystyrene spheres, pollen and spores of known different diameters. The results indicated that absolute particle diameters can be measured within a precision of approximately 1 mu using instruments for flow cytofluorometry.", "contents": "Estimation of cell size from pulse shape in flow cytofluorometry. The fluorescence pulse widths (pulse duration) generated by fluorochromed cells in a flow-through cytofluorometer provide useful information regarding cell (or nuclear) size and possibly other morphologic features. Simple fixed thresholds just above background noise can be used to identify these pulses, but measurements are then strongly affected by random noise and will vary as a result of both pulse amplitude and pulse shape. In this paper, we propose two alternative, amplitude-independent estimates of pulse width. The first is based on a threshold at some fraction of pulse height, or on a pair of thresholds scaled to some fixed central fraction of the total integrated intensity. The second is based on the ratio of pulse area to peak height. The quantitative properties of these width estimators is studied with simulated fluorescence pulses and with experimental specimens of fluorchromed polystyrene spheres, pollen and spores of known different diameters. The results indicated that absolute particle diameters can be measured within a precision of approximately 1 mu using instruments for flow cytofluorometry."} {"id": "PMID:1254923", "title": "Cell discrimination by multiangle light scattering.", "content": "Measurement of the light scattered by biological cells as a function of scattering angle provides information that can be correlated with cell type. Two flow systems that provide multiangle scattering data from cells have been constructed and tested. The first utilizes two narrow-aperture detectors positioned at different angles; the second utilizes the motion of the cell to generate complete scatter patterns of individual cells over a 67 degrees range of scattering angle.", "contents": "Cell discrimination by multiangle light scattering. Measurement of the light scattered by biological cells as a function of scattering angle provides information that can be correlated with cell type. Two flow systems that provide multiangle scattering data from cells have been constructed and tested. The first utilizes two narrow-aperture detectors positioned at different angles; the second utilizes the motion of the cell to generate complete scatter patterns of individual cells over a 67 degrees range of scattering angle."} {"id": "PMID:1254924", "title": "Flow microfluorometric and light-scatter measurement of nuclear and cytoplasmic size in mammalian cells.", "content": "A technique for rapid measurement of nuclear and cytoplasmic size relationships in mammalian cell populations has been developed. Based on fluorescence staining of either the nucleus alone or in combination with the cytoplasm using two-color fluorescence methods, this technique permits the simultaneous determination of nuclear and cytoplasmic diameters from fluorescence and light-scatter measurements. Cells stained in liquid suspension pass through a flow chamber at a constant velocity, intersecting a laser beam which excites cell fluorescence and causes light scatter. Depending upon which analysis procedure is used, optical sensors measure nuclear fluorescence and light scatter (whole cell size) or two-color nuclear and cytoplasmic fluorescence from individual cells crossing the laser beam. The time durations of signals generated by the nucleus and cytoplasm are converted electronically into signals proportional to the respective diameters and are displayed as frequency distribution hitograms. Illustrative examples of measurements on uniform microspheres, cultured mammalian cells and human exfoliated gynecologic cells are presented.", "contents": "Flow microfluorometric and light-scatter measurement of nuclear and cytoplasmic size in mammalian cells. A technique for rapid measurement of nuclear and cytoplasmic size relationships in mammalian cell populations has been developed. Based on fluorescence staining of either the nucleus alone or in combination with the cytoplasm using two-color fluorescence methods, this technique permits the simultaneous determination of nuclear and cytoplasmic diameters from fluorescence and light-scatter measurements. Cells stained in liquid suspension pass through a flow chamber at a constant velocity, intersecting a laser beam which excites cell fluorescence and causes light scatter. Depending upon which analysis procedure is used, optical sensors measure nuclear fluorescence and light scatter (whole cell size) or two-color nuclear and cytoplasmic fluorescence from individual cells crossing the laser beam. The time durations of signals generated by the nucleus and cytoplasm are converted electronically into signals proportional to the respective diameters and are displayed as frequency distribution hitograms. Illustrative examples of measurements on uniform microspheres, cultured mammalian cells and human exfoliated gynecologic cells are presented."} {"id": "PMID:1254925", "title": "Pulse-height light-scatter distributions using flow-systems instrumentation.", "content": "Several laboratories have recently been making light-scatter measurements on cells and other particles using flow-systems instrumentation. We at the Los Alamos Scientific Laboratory, as well as others, have obtained multimodal pulse-height distributions in certain angular regimes from particles of supposedly uniform characteristics. Because it was assumed that multimodal distributions implied characteristics of multivalue, the accuracy of such data has been doubted. In the present work, pulse-height distributions anticipated on the basis of exact electromagnetic theory were calculated for particles of known characteristics. These calculated pulse-height distributions agree quite well with those obtained experimentally. Physical optics form the basis for the explanation of the complex pulse-height distributions obtained experimentally. However, the results of this study show that certain cautions are necessary in the interpretation of light-scatter data presented in this manner.", "contents": "Pulse-height light-scatter distributions using flow-systems instrumentation. Several laboratories have recently been making light-scatter measurements on cells and other particles using flow-systems instrumentation. We at the Los Alamos Scientific Laboratory, as well as others, have obtained multimodal pulse-height distributions in certain angular regimes from particles of supposedly uniform characteristics. Because it was assumed that multimodal distributions implied characteristics of multivalue, the accuracy of such data has been doubted. In the present work, pulse-height distributions anticipated on the basis of exact electromagnetic theory were calculated for particles of known characteristics. These calculated pulse-height distributions agree quite well with those obtained experimentally. Physical optics form the basis for the explanation of the complex pulse-height distributions obtained experimentally. However, the results of this study show that certain cautions are necessary in the interpretation of light-scatter data presented in this manner."} {"id": "PMID:1254926", "title": "Slit-scan cytofluorometry. Basis for automated prescreening of urinary tract cytology.", "content": "A study was undertaken to assess the applicability of the slit-scan technique to automated prescreening of urinary tract cytology. Cells from voided and catheterized urines were stained with acridine orange and measured on a static cell slit-scan cytofluorometer. Analysis of data from the specimens indicates that nuclear fluorescence alone appears adequate for recognition of abnormal specimens. Remaining problems in the automation of urinary tract cytology prescreening are discussed.", "contents": "Slit-scan cytofluorometry. Basis for automated prescreening of urinary tract cytology. A study was undertaken to assess the applicability of the slit-scan technique to automated prescreening of urinary tract cytology. Cells from voided and catheterized urines were stained with acridine orange and measured on a static cell slit-scan cytofluorometer. Analysis of data from the specimens indicates that nuclear fluorescence alone appears adequate for recognition of abnormal specimens. Remaining problems in the automation of urinary tract cytology prescreening are discussed."} {"id": "PMID:1254927", "title": "Flow microfluorometric system for screening gynecologic cytology specimens using propidium iodide-fluorescein isothiocyanate.", "content": "Seventy cervical cytology specimens have been screened by a xero resolution flow analyzer-sorter using propidium iodide and fluorescein isothiocyanate as fluorochromes for nucleus and cytoplasm, respectively. This system shows a 1% sensitivity for detection of abnormal cells using only crude visual data analysis. Screening of clinical specimens was performed on the instrument with a 5.8% false negative rate and a 11.8% false positive rate by comparison with routine visual cytologic evaluation of the same samples.", "contents": "Flow microfluorometric system for screening gynecologic cytology specimens using propidium iodide-fluorescein isothiocyanate. Seventy cervical cytology specimens have been screened by a xero resolution flow analyzer-sorter using propidium iodide and fluorescein isothiocyanate as fluorochromes for nucleus and cytoplasm, respectively. This system shows a 1% sensitivity for detection of abnormal cells using only crude visual data analysis. Screening of clinical specimens was performed on the instrument with a 5.8% false negative rate and a 11.8% false positive rate by comparison with routine visual cytologic evaluation of the same samples."} {"id": "PMID:1254928", "title": "Studies of cellular differentiation by automated cell separation. Two model systems: Friend virus-transformed cells and Hydra attenuata.", "content": "The automated high-speed analysis and separation of cells on the basis of spectroscopic parameters has been applied to studies of cellular differentiation in two systems. The temporal changes following induction of differentiation by dimethylsulfoxide in the Friend virus-transformed erythroid cells were quantitated by multiparameter analysis leading to the separation of discrete subpopulations. Thus, following induction, cell size decreased as measured by light scattering, the number of H-2 histocompatibility antigen sites decreased as measured by indirect fluorescent antibody binding, the number of lectin-binding sites per cell increased as measured by fluorescein-labeled concanavalin-A and the microviscosity of the hydrocarbon region of the plasma membrane increased as determined by the fluorescence emission anisotropy of the membrane probe 1,6-diphenyl-1,3,5-hexatriene. Cells were separated on the basis of several of these parameters and analyzed for their hemogloglobin content by benzidine staining. Examination of cells separated according to the anisotropy parameter showed that high anisotropy values were correlated with (a) small cell size, (b) positive staining with benzidine and (c) pronounced reactivity with fluorescent antibody to the erythrocyte protein spectrin. Disaggregated cells from Hydra attenuata were selectively stained with the dyes rhodanile blue, 7-(p-methoxybenzylamino)-4-nitrobenz-2-oxa-1,3-diazole and fluorescamine. Distribution analyses and preliminary separations indicated the feasibility of obtaining homogeneous classes of cell types in a viable state. The experiments with emission anisotropy represent the first analyses and separations of single cells on the basis of fluorescence polarization. Many other uses of this technique are anticipated.", "contents": "Studies of cellular differentiation by automated cell separation. Two model systems: Friend virus-transformed cells and Hydra attenuata. The automated high-speed analysis and separation of cells on the basis of spectroscopic parameters has been applied to studies of cellular differentiation in two systems. The temporal changes following induction of differentiation by dimethylsulfoxide in the Friend virus-transformed erythroid cells were quantitated by multiparameter analysis leading to the separation of discrete subpopulations. Thus, following induction, cell size decreased as measured by light scattering, the number of H-2 histocompatibility antigen sites decreased as measured by indirect fluorescent antibody binding, the number of lectin-binding sites per cell increased as measured by fluorescein-labeled concanavalin-A and the microviscosity of the hydrocarbon region of the plasma membrane increased as determined by the fluorescence emission anisotropy of the membrane probe 1,6-diphenyl-1,3,5-hexatriene. Cells were separated on the basis of several of these parameters and analyzed for their hemogloglobin content by benzidine staining. Examination of cells separated according to the anisotropy parameter showed that high anisotropy values were correlated with (a) small cell size, (b) positive staining with benzidine and (c) pronounced reactivity with fluorescent antibody to the erythrocyte protein spectrin. Disaggregated cells from Hydra attenuata were selectively stained with the dyes rhodanile blue, 7-(p-methoxybenzylamino)-4-nitrobenz-2-oxa-1,3-diazole and fluorescamine. Distribution analyses and preliminary separations indicated the feasibility of obtaining homogeneous classes of cell types in a viable state. The experiments with emission anisotropy represent the first analyses and separations of single cells on the basis of fluorescence polarization. Many other uses of this technique are anticipated."} {"id": "PMID:1254929", "title": "Purification of the chromosomes of the Indian muntjac by flow sorting.", "content": "Metaphase chromosomes were isolated from a male Indian muntjac cell line, were stained with ethidium bromide and were analyzed by flow microfluorometry to establish a deoxyribonucleic acid (DNA)-based karyotype. Five major peaks were evident on the chromosomal DNA distribution corresponding to the five chromosome types in this species. The amount of DNA in each chromosome was confirmed by cytophotometric measurements of intact metaphase spreads. The five chromosome types were separated by flow sorting at rates up to several hundred chromosomes per second. The sorted chromosomes were identified by morphology and by Giemsa banding patterns. The automsomes, Numbers 1, 2 and 3, and the X + 3 composite chromosome were separated with a high degree of purity (90%). The centromere region of the X + 3 chromosome was fragile to mechanical shearing, and during isolation a small proportion of these chromosomes broke into four segiments: the long arm, the short arm, the short arm plus centromere and the centromere region. A large fraction of the constitutive heterochromatin of this species is present in the centromere region of the X + 3 chromosome and in the Y chromosome; these two regions possess similar amounts of DNA and therefore sort together. Chromosome flow sorting is rapid, reproducible and precise; it allows the collection of microgram quantities of purified chromosomes.", "contents": "Purification of the chromosomes of the Indian muntjac by flow sorting. Metaphase chromosomes were isolated from a male Indian muntjac cell line, were stained with ethidium bromide and were analyzed by flow microfluorometry to establish a deoxyribonucleic acid (DNA)-based karyotype. Five major peaks were evident on the chromosomal DNA distribution corresponding to the five chromosome types in this species. The amount of DNA in each chromosome was confirmed by cytophotometric measurements of intact metaphase spreads. The five chromosome types were separated by flow sorting at rates up to several hundred chromosomes per second. The sorted chromosomes were identified by morphology and by Giemsa banding patterns. The automsomes, Numbers 1, 2 and 3, and the X + 3 composite chromosome were separated with a high degree of purity (90%). The centromere region of the X + 3 chromosome was fragile to mechanical shearing, and during isolation a small proportion of these chromosomes broke into four segiments: the long arm, the short arm, the short arm plus centromere and the centromere region. A large fraction of the constitutive heterochromatin of this species is present in the centromere region of the X + 3 chromosome and in the Y chromosome; these two regions possess similar amounts of DNA and therefore sort together. Chromosome flow sorting is rapid, reproducible and precise; it allows the collection of microgram quantities of purified chromosomes."} {"id": "PMID:1254930", "title": "Assessment of monocyte esterase activity by flow cytophotometry.", "content": "An azo dye supravital method has been devised for selectively staining human monocytes in suspension for nonspecific esterase activity. Stained cells can be identified and rapidly enumerated by presenting the suspension of stained cells to the Cytograf, a flow-through cell discriminating cytophotometer. The intensity of stain is proportional to the intracellular esterase activity. By analysis of the oscilloscope display, it has been possible to obtain relative data concerning the degree of activity of monocyte nonspecific esterase activity. These observations suggest a unique approach to the measurement of intracellular enzyme activity in selected cells in a mixed population.", "contents": "Assessment of monocyte esterase activity by flow cytophotometry. An azo dye supravital method has been devised for selectively staining human monocytes in suspension for nonspecific esterase activity. Stained cells can be identified and rapidly enumerated by presenting the suspension of stained cells to the Cytograf, a flow-through cell discriminating cytophotometer. The intensity of stain is proportional to the intracellular esterase activity. By analysis of the oscilloscope display, it has been possible to obtain relative data concerning the degree of activity of monocyte nonspecific esterase activity. These observations suggest a unique approach to the measurement of intracellular enzyme activity in selected cells in a mixed population."} {"id": "PMID:1254931", "title": "Automated analysis of antigen-stimulated lymphocytes.", "content": "Human peripheral blood lymphocytes were stimulated with phytohemagglutinin and tuberculin-purified protein derivative to determine if flow microfluorometric techniques had the sensitivity to detect high and low levels of blastogenic response. The deoxyribonucleic acid content of the lymphocytes was analyzed after culture. Blastogenic response was found to be measurable both sensitively and reproducibly. Tritiated thymidine incorporation measurements were also made. Preliminary experiments using inactivated Herpesvirion (type I) as a stimulant showed blastogenic response detectable by flow microfluorometric deoxyribonucleic acid measurements. Refinements of this technique may prove to be useful in the study of lymphocyte response to viral antigens in patient populations.", "contents": "Automated analysis of antigen-stimulated lymphocytes. Human peripheral blood lymphocytes were stimulated with phytohemagglutinin and tuberculin-purified protein derivative to determine if flow microfluorometric techniques had the sensitivity to detect high and low levels of blastogenic response. The deoxyribonucleic acid content of the lymphocytes was analyzed after culture. Blastogenic response was found to be measurable both sensitively and reproducibly. Tritiated thymidine incorporation measurements were also made. Preliminary experiments using inactivated Herpesvirion (type I) as a stimulant showed blastogenic response detectable by flow microfluorometric deoxyribonucleic acid measurements. Refinements of this technique may prove to be useful in the study of lymphocyte response to viral antigens in patient populations."} {"id": "PMID:1254932", "title": "Quantitation of lymphocyte response to antigen by flow cytofluorometry.", "content": "The response of human peripheral blood lymphocytes to antigenic stimulation has been studied in vitro using flow cytofluorometry and an acridine orange (AO) staining technique for cellular deoxyribonucleic acid and ribonucleic acid (RNA). Antigen-stimulated \"pyroninophillic\" immunoblasts, identified by an increase in cellular content of RNA (red fluorescence with AO), were quantitated in triplicate cultures incubated up to 7 days with and without bacterial antigen. These results were similar to 14C-thymidine incorporation into identical cultures incubated in parallel. Cytofluorometric analysis showed a peak in percentage of immunoblasts after 6 days in culture, while maximum thymidine incorporation was seen on day 7. Cells from patients with depressed immune response secondary to cancer showed lower than normal antigen response by cytofluorometry. Kinetic studies revealed both a lower percentage of immunoblasts when compared to normal and a lower average per cell RNA content of the stimulated cells. AO cytofluorometry is suggested as a convenient method of simultaneously assessing lymphocyte proliferative and nonproliferative response to antigen.", "contents": "Quantitation of lymphocyte response to antigen by flow cytofluorometry. The response of human peripheral blood lymphocytes to antigenic stimulation has been studied in vitro using flow cytofluorometry and an acridine orange (AO) staining technique for cellular deoxyribonucleic acid and ribonucleic acid (RNA). Antigen-stimulated \"pyroninophillic\" immunoblasts, identified by an increase in cellular content of RNA (red fluorescence with AO), were quantitated in triplicate cultures incubated up to 7 days with and without bacterial antigen. These results were similar to 14C-thymidine incorporation into identical cultures incubated in parallel. Cytofluorometric analysis showed a peak in percentage of immunoblasts after 6 days in culture, while maximum thymidine incorporation was seen on day 7. Cells from patients with depressed immune response secondary to cancer showed lower than normal antigen response by cytofluorometry. Kinetic studies revealed both a lower percentage of immunoblasts when compared to normal and a lower average per cell RNA content of the stimulated cells. AO cytofluorometry is suggested as a convenient method of simultaneously assessing lymphocyte proliferative and nonproliferative response to antigen."} {"id": "PMID:1254933", "title": "A generalized machine for automated flow cytology system design.", "content": "A general-purpose multiparameter flow cytophotometry system has been developed for use in the desgin of flow cytophotometers to perform specific tasks in automated cytology. Five separate measurement stations spaced along the axis of a capillary tube can be used to make up to eight optical measurements of individual cells flowing through the capillary. The system uses a broad-band arc source and can measure light scattered at various angles, light absorption by cell constituents and/or dyes and fluorescence of cell constituents and/or fluorochromes, excited directly and/or by energy transfer from neighboring molecules. High numerical aperture optics are used to maximize light-gathering capacity and minimize the effects of cell orientation and eccentricity of position in the fluid stream on measurements. A hard-wired preprocessor is used to detect the presence of cells and adjust sampling timing for changes in cell velocity; the electronic system also controls the gain of the detector photomultiplier tubes to compensate for background variations. Data acquistion and analysis are controled by a small general-purpose digital computer. The system has been used to develop a method and apparatus for blood cell counting and classification.", "contents": "A generalized machine for automated flow cytology system design. A general-purpose multiparameter flow cytophotometry system has been developed for use in the desgin of flow cytophotometers to perform specific tasks in automated cytology. Five separate measurement stations spaced along the axis of a capillary tube can be used to make up to eight optical measurements of individual cells flowing through the capillary. The system uses a broad-band arc source and can measure light scattered at various angles, light absorption by cell constituents and/or dyes and fluorescence of cell constituents and/or fluorochromes, excited directly and/or by energy transfer from neighboring molecules. High numerical aperture optics are used to maximize light-gathering capacity and minimize the effects of cell orientation and eccentricity of position in the fluid stream on measurements. A hard-wired preprocessor is used to detect the presence of cells and adjust sampling timing for changes in cell velocity; the electronic system also controls the gain of the detector photomultiplier tubes to compensate for background variations. Data acquistion and analysis are controled by a small general-purpose digital computer. The system has been used to develop a method and apparatus for blood cell counting and classification."} {"id": "PMID:1254934", "title": "Cytofluorometric studies on conformation of nucleic acids in situ. I. Restriction of acridine orange binding by chromatin proteins.", "content": "Binding of the fluorochrome acridine orange (AO) to nucleic acids in situ is studied by automated cytofluorometry in two differentiating cell systems: Friend virus-transformed murine erythroleukemia induced to differentiate by dimethyl sulfoxide, and phytohemagglutinin-stimulated human lymphocytes. The specificity of the stain for deoxyribonucleic acid is discussed on the basis of data obtained by cell treatment with nucleases. Evidence is presented that in the case of Friend leukemia cells, but not phytohemagglutinin-stimulated lymphocytes, a significant change in the number of AO-intercalating sites in DNA occurrs during differentiation. These results suggest that changes in nuclear chromatin occurring during cell differentiation may be correlated, in some but not all systems, with changes in accessibility of DNA in situ to intercalating dyes. The role of divalent cations, especially Mg2+, in the conformation of nuclear chromatin and in modulation of the accessibility of nucleic acids to AO is discussed. The method provides a tool for the study of nucleic acid-protein interaction in situ, and in some cell systems it may be applicable as a marker for recognition of cell transformation, differentiation or neoplasia.", "contents": "Cytofluorometric studies on conformation of nucleic acids in situ. I. Restriction of acridine orange binding by chromatin proteins. Binding of the fluorochrome acridine orange (AO) to nucleic acids in situ is studied by automated cytofluorometry in two differentiating cell systems: Friend virus-transformed murine erythroleukemia induced to differentiate by dimethyl sulfoxide, and phytohemagglutinin-stimulated human lymphocytes. The specificity of the stain for deoxyribonucleic acid is discussed on the basis of data obtained by cell treatment with nucleases. Evidence is presented that in the case of Friend leukemia cells, but not phytohemagglutinin-stimulated lymphocytes, a significant change in the number of AO-intercalating sites in DNA occurrs during differentiation. These results suggest that changes in nuclear chromatin occurring during cell differentiation may be correlated, in some but not all systems, with changes in accessibility of DNA in situ to intercalating dyes. The role of divalent cations, especially Mg2+, in the conformation of nuclear chromatin and in modulation of the accessibility of nucleic acids to AO is discussed. The method provides a tool for the study of nucleic acid-protein interaction in situ, and in some cell systems it may be applicable as a marker for recognition of cell transformation, differentiation or neoplasia."} {"id": "PMID:1254935", "title": "Cytofluorometric studies on conformation of nucleic acids in situ. II. Denaturation of deoxyribonucleic acid.", "content": "Thermal denaturation of deoxyribonucleic acid (DNA) in situ in individual unbroken cells is studied by a cytofluorometric method. This method allows us to investigate DNA denaturation in the presence of divalent cations at concentrations reported to be necessary to maintain native structure of nuclear chromatin. Under these conditions the pattern of DNA denaturation is very different than when studied in the presence of ethylenediaminetetraacetate or citrate. The results suggest that with divalent cations present, the histone basic charges are more uniformly distributed along whole nuclear DNA. Various cell types exhibit great differences in sensitivity to DNA denaturation when assayed in the presence of 1 mM MgCl2. Human lymphocytes, monocytes and certain kinds of human leukemic cells show differences large enough to be used as a parameter for their recognition in mixed samples. Possible applications of the method in basic research on chromatin conformation and as a tool for cell recognition in diagnostic cytology or in the classification of human leukemia are proposed.", "contents": "Cytofluorometric studies on conformation of nucleic acids in situ. II. Denaturation of deoxyribonucleic acid. Thermal denaturation of deoxyribonucleic acid (DNA) in situ in individual unbroken cells is studied by a cytofluorometric method. This method allows us to investigate DNA denaturation in the presence of divalent cations at concentrations reported to be necessary to maintain native structure of nuclear chromatin. Under these conditions the pattern of DNA denaturation is very different than when studied in the presence of ethylenediaminetetraacetate or citrate. The results suggest that with divalent cations present, the histone basic charges are more uniformly distributed along whole nuclear DNA. Various cell types exhibit great differences in sensitivity to DNA denaturation when assayed in the presence of 1 mM MgCl2. Human lymphocytes, monocytes and certain kinds of human leukemic cells show differences large enough to be used as a parameter for their recognition in mixed samples. Possible applications of the method in basic research on chromatin conformation and as a tool for cell recognition in diagnostic cytology or in the classification of human leukemia are proposed."} {"id": "PMID:1254936", "title": "Quantitation of fluorescence fading phenomena for identifying intracellular biopolymers.", "content": "The fading behavior of the 670 nm fluorescence emission band produced by unfixed rat mast cells stained with acridine orange (AO) has been found to be in excellent agreement with the behavior predicted by second order chemical kinetics. The reciprocal of fluorescence intensity plotted against time yields a straight line. When due account is taken of dye/cell ratio and the intensity of fluorescence-exciting radiation, Io (measured with the standard phosphor particle), the slope of this straight line is a constant, k'', which is independent of dye/cell ratio and Io. k'' differs from the second order photochemical rate constant by a constant factor. The fading of a given AO-biopolymer complex is described by a particular value of k''. Two values of k'' have been found for rat mast cell granules, indicating the presence of two different AO-biopolymer complexes. Fading of fluorescence may serve to identify particular intracellular biopolymers in individual cells even when present in a heterogeneous population.", "contents": "Quantitation of fluorescence fading phenomena for identifying intracellular biopolymers. The fading behavior of the 670 nm fluorescence emission band produced by unfixed rat mast cells stained with acridine orange (AO) has been found to be in excellent agreement with the behavior predicted by second order chemical kinetics. The reciprocal of fluorescence intensity plotted against time yields a straight line. When due account is taken of dye/cell ratio and the intensity of fluorescence-exciting radiation, Io (measured with the standard phosphor particle), the slope of this straight line is a constant, k'', which is independent of dye/cell ratio and Io. k'' differs from the second order photochemical rate constant by a constant factor. The fading of a given AO-biopolymer complex is described by a particular value of k''. Two values of k'' have been found for rat mast cell granules, indicating the presence of two different AO-biopolymer complexes. Fading of fluorescence may serve to identify particular intracellular biopolymers in individual cells even when present in a heterogeneous population."} {"id": "PMID:1254937", "title": "Quantitation of the rate-zonal sedimentation spectrum.", "content": "Rate-zonal sedimentation of cells from the female genital tract has been employed as a means of separating many of the different cellular components from each other. Ultra-slow streak photography of forward scattered light from the sedimentation spectrum has been used as a monitor of the success of the individual sedimentation maneuver. The presence of convention currents vitiates the separation potential of the technique, and this is readily detected by the photographic monitor. In addition, these photographs clearly indicate the positions of bands of cellular entities of different sedimentation velocities. Further study of the quantitative aspects of the light scattered from each part of the spectrum reveals that it possesses a quantitative representation of the concentration of cells at each level of the spectrum. The photographs and densitometric scans support these expectations. To avoid the limitations of film as a data-logging medium and to obtain real-time system utilization, a direct photoelectric scanner has been assembled. Preliminary tests indicate ready feasibility.", "contents": "Quantitation of the rate-zonal sedimentation spectrum. Rate-zonal sedimentation of cells from the female genital tract has been employed as a means of separating many of the different cellular components from each other. Ultra-slow streak photography of forward scattered light from the sedimentation spectrum has been used as a monitor of the success of the individual sedimentation maneuver. The presence of convention currents vitiates the separation potential of the technique, and this is readily detected by the photographic monitor. In addition, these photographs clearly indicate the positions of bands of cellular entities of different sedimentation velocities. Further study of the quantitative aspects of the light scattered from each part of the spectrum reveals that it possesses a quantitative representation of the concentration of cells at each level of the spectrum. The photographs and densitometric scans support these expectations. To avoid the limitations of film as a data-logging medium and to obtain real-time system utilization, a direct photoelectric scanner has been assembled. Preliminary tests indicate ready feasibility."} {"id": "PMID:1254938", "title": "A new optical multichannel microspectrofluorometer.", "content": "A new microspectrofluorometer has been developed that combines a photometric fluorescence microscope with an optical multichannel analyzer. This instrument provides fluorescence emission spectra of biological materials by detecting the entire spectrum simultaneously in real time. These spectra are subsequently recorded and corrected so as to identify the fluorescent reaction products or to test whether fluorescent cytochemical probes bind to the expected substrate within cells. The procedures and advantages of optical multichannel analysis are described, and an application of microspectrofluorometry to acriflavine-Feulgen cytochemistry is given.", "contents": "A new optical multichannel microspectrofluorometer. A new microspectrofluorometer has been developed that combines a photometric fluorescence microscope with an optical multichannel analyzer. This instrument provides fluorescence emission spectra of biological materials by detecting the entire spectrum simultaneously in real time. These spectra are subsequently recorded and corrected so as to identify the fluorescent reaction products or to test whether fluorescent cytochemical probes bind to the expected substrate within cells. The procedures and advantages of optical multichannel analysis are described, and an application of microspectrofluorometry to acriflavine-Feulgen cytochemistry is given."} {"id": "PMID:1254939", "title": "Microfluorimetric quantitation of catecholamine fluorescence in rat median eminence. I. Aspects on the distribution of dopamine and noradrenaline nerve terminals.", "content": "Using the fluorescence histochemical technique of Falck and Hillarp, a quantitative microfluorimetric study of the catecholamine fluorescence in the median eminence has been performed. On the basis of morphologic criteria, the median eminence was subdivided into various areas from which the microfluorimetric measurements were made; the subependymal layer, the medial and lateral palisade zone of the rostral and the central and caudal region of the median eminence (for definitions of the various areas and regions, see Anatomical Subdivision). The highest fluorescence intensities were recorded from the lateral palisade zone, indicating that this area has the most dense catecholamine innervation, whereas the lowest fluorescence intensities were recorded from the subependymal layer. Dopamine-beta-hydroxylase inhibition produced by FLA-63, fusaric acid or diethyldithiocarbamate resulted in all cases in a 50-70% reduction of the catecholamine fluorescence in the subependymal layer, whereas only minute effects were observed in the lateral palisade zone. In the medial palisade zone, these treatments generally led to a substantial reduction (30-50%) of the catecholamine fluorescence. Basal hypothalamic deafferentation according to Halasz, or lesioning of the ventral catecholamine bundle, produced an almost complete disappearance of the fluorescence in the subependymal layer, while both procedures were largely ineffective in affecting the catecholamine fluorescence in the lateral palisade zone. On basal hypothalamic deafferentation the catecholamine fluorescence in the medial palisade zone was markedly reduced (40-60%), while the ventral bundle lesions were less efficient in this respect. From the present results it is suggested that the subependymal layer is mainly innervated by noradrenaline nerve terminals and the lateral palisade zone is mainly innervated by dopamine nerve terminals, whereas the medial palisade zone receives a mixed innervation of dopamine and noradrenaline terminals, the dopamine proportion being in the order of 50-75% of total catecholamine content.", "contents": "Microfluorimetric quantitation of catecholamine fluorescence in rat median eminence. I. Aspects on the distribution of dopamine and noradrenaline nerve terminals. Using the fluorescence histochemical technique of Falck and Hillarp, a quantitative microfluorimetric study of the catecholamine fluorescence in the median eminence has been performed. On the basis of morphologic criteria, the median eminence was subdivided into various areas from which the microfluorimetric measurements were made; the subependymal layer, the medial and lateral palisade zone of the rostral and the central and caudal region of the median eminence (for definitions of the various areas and regions, see Anatomical Subdivision). The highest fluorescence intensities were recorded from the lateral palisade zone, indicating that this area has the most dense catecholamine innervation, whereas the lowest fluorescence intensities were recorded from the subependymal layer. Dopamine-beta-hydroxylase inhibition produced by FLA-63, fusaric acid or diethyldithiocarbamate resulted in all cases in a 50-70% reduction of the catecholamine fluorescence in the subependymal layer, whereas only minute effects were observed in the lateral palisade zone. In the medial palisade zone, these treatments generally led to a substantial reduction (30-50%) of the catecholamine fluorescence. Basal hypothalamic deafferentation according to Halasz, or lesioning of the ventral catecholamine bundle, produced an almost complete disappearance of the fluorescence in the subependymal layer, while both procedures were largely ineffective in affecting the catecholamine fluorescence in the lateral palisade zone. On basal hypothalamic deafferentation the catecholamine fluorescence in the medial palisade zone was markedly reduced (40-60%), while the ventral bundle lesions were less efficient in this respect. From the present results it is suggested that the subependymal layer is mainly innervated by noradrenaline nerve terminals and the lateral palisade zone is mainly innervated by dopamine nerve terminals, whereas the medial palisade zone receives a mixed innervation of dopamine and noradrenaline terminals, the dopamine proportion being in the order of 50-75% of total catecholamine content."} {"id": "PMID:1254940", "title": "Microfluorimetric quantitation of catecholamine fluorescence in rat median eminence. II. Turnover changes in hormonal states.", "content": "Catecholamine nerve terminals in the rat median eminence have been studied using the fluorescence histochemical technique of Falck and Hillarp in combination with quantitative microfluorimetry. The catecholamine fluorescence intensities recorded from various parts of the median eminence were all found to be within the linear part of the dopamine or noradrenaline concentration-fluorescence relationship as studied in an agar-albumin model system. The catecholamine fluorescence was also found to disappear with time in an exponential manner following tyrosine hydroxylase inhibition produced by alpha-methyl-p-tyrosine methylester (H44/68). Similar results were obtained when measuring the dopamine decline by mass fragmentography in the median eminence after H44/68 treatment. These results and analysis of fluorescence frequency histograms strongly indicate that the catecholamine fluorescence values recorded are proportional to the catecholamine concentration. It is concluded that the microfluorimetric technique used is a reliable method for catecholamine quantitation in discrete nerve terminal areas of the median eminence. The main advantages of the technique are that a high sensitivity and quantitative data on the transmitter content can be obtained in strict relation to the neuroanatomy. Measurement of the catecholamine fluorescence disappearance after H44/68 was used to evaluate catecholamine turnover during various endocrine states. The results showed that two dopamine systems with different transmitter turnover may be distinguished. Tuberinfundibular dopamine neurons projecting to the lateral palisade zone were thus shown to have a slower turnover than those projecting medially to the capillary loops. No definite changes in catecholamine turnover were observed after adrenalectomy and castration in the male, although there was a tendency toward increased noradrenaline turnover in both states. During pregnancy an increase in noradrenaline as well as dopamine turnover was noted. The present results therefore give further evidence for the view that catecholamine nerve terminals in the median eminence may participate in the regulation of gonadotrophin secretion.", "contents": "Microfluorimetric quantitation of catecholamine fluorescence in rat median eminence. II. Turnover changes in hormonal states. Catecholamine nerve terminals in the rat median eminence have been studied using the fluorescence histochemical technique of Falck and Hillarp in combination with quantitative microfluorimetry. The catecholamine fluorescence intensities recorded from various parts of the median eminence were all found to be within the linear part of the dopamine or noradrenaline concentration-fluorescence relationship as studied in an agar-albumin model system. The catecholamine fluorescence was also found to disappear with time in an exponential manner following tyrosine hydroxylase inhibition produced by alpha-methyl-p-tyrosine methylester (H44/68). Similar results were obtained when measuring the dopamine decline by mass fragmentography in the median eminence after H44/68 treatment. These results and analysis of fluorescence frequency histograms strongly indicate that the catecholamine fluorescence values recorded are proportional to the catecholamine concentration. It is concluded that the microfluorimetric technique used is a reliable method for catecholamine quantitation in discrete nerve terminal areas of the median eminence. The main advantages of the technique are that a high sensitivity and quantitative data on the transmitter content can be obtained in strict relation to the neuroanatomy. Measurement of the catecholamine fluorescence disappearance after H44/68 was used to evaluate catecholamine turnover during various endocrine states. The results showed that two dopamine systems with different transmitter turnover may be distinguished. Tuberinfundibular dopamine neurons projecting to the lateral palisade zone were thus shown to have a slower turnover than those projecting medially to the capillary loops. No definite changes in catecholamine turnover were observed after adrenalectomy and castration in the male, although there was a tendency toward increased noradrenaline turnover in both states. During pregnancy an increase in noradrenaline as well as dopamine turnover was noted. The present results therefore give further evidence for the view that catecholamine nerve terminals in the median eminence may participate in the regulation of gonadotrophin secretion."} {"id": "PMID:1254941", "title": "Simultaneous visualization by light microscopy of two pituitary hormones in a single tissue section using a combination of indirect immunohistochemical methods.", "content": "Two indirect methods involving enzyme-labeled antibodies were used to demonstrate simultaneously two distinct tissue antigens in the same histologic section without a need for antigen-antibody dissociative procedures. Sections of rat pituitary gland were incubated with rabbit anti-rat luteinizing hormone followed by goat anti-rabbit gamma-globulin conjugated to horseradish peroxidase. The same sections were then further incubated with monkey anti-rat growth hormone followed by goat anti-monkey gamma-globulin conjugated to glucose oxidase. Antigenic luteinizing hormone was subsequently localized with hydrogen peroxide-3,3'-diaminobenzidine as substrate for peroxidase, and growth hormone was localized with a glucose-phenazine methosulfate-nitroblue tetrazolium mixture as a substrate for glucose oxidase. The method relies on the availability of specific primary antibodies raised in different animal species in addition to corresponding specific secondary antibodies linked covalently to separate enzymes.", "contents": "Simultaneous visualization by light microscopy of two pituitary hormones in a single tissue section using a combination of indirect immunohistochemical methods. Two indirect methods involving enzyme-labeled antibodies were used to demonstrate simultaneously two distinct tissue antigens in the same histologic section without a need for antigen-antibody dissociative procedures. Sections of rat pituitary gland were incubated with rabbit anti-rat luteinizing hormone followed by goat anti-rabbit gamma-globulin conjugated to horseradish peroxidase. The same sections were then further incubated with monkey anti-rat growth hormone followed by goat anti-monkey gamma-globulin conjugated to glucose oxidase. Antigenic luteinizing hormone was subsequently localized with hydrogen peroxide-3,3'-diaminobenzidine as substrate for peroxidase, and growth hormone was localized with a glucose-phenazine methosulfate-nitroblue tetrazolium mixture as a substrate for glucose oxidase. The method relies on the availability of specific primary antibodies raised in different animal species in addition to corresponding specific secondary antibodies linked covalently to separate enzymes."} {"id": "PMID:1254942", "title": "Aurothiomalate as an ultrastructural marker. Electron microscopy and x-ray microanalysis of various tissues after in vivo gold injections.", "content": "Rabbits and rats were given single injections of aurothiomalate by different routes. The animals were killed at progressive intervals, and sections from various organs were examined by electron microscopic x-ray microanalysis. Ultrastructurally, characteristic material was regularly found in vacuoles, dense and heterogeneous bodies of macrophages, hepatocytes and renal epithelial cells. Occasionally, other mesenchymal cells also contained gold. Histochemical and analytical tests showed that the gold-containing organelles were devoid of acid phosphatase activity. The generalized rapid spread, retention and selectivity of localization after a single small dose make aurothiomalate a useful marker substance for ultrastructural studies.", "contents": "Aurothiomalate as an ultrastructural marker. Electron microscopy and x-ray microanalysis of various tissues after in vivo gold injections. Rabbits and rats were given single injections of aurothiomalate by different routes. The animals were killed at progressive intervals, and sections from various organs were examined by electron microscopic x-ray microanalysis. Ultrastructurally, characteristic material was regularly found in vacuoles, dense and heterogeneous bodies of macrophages, hepatocytes and renal epithelial cells. Occasionally, other mesenchymal cells also contained gold. Histochemical and analytical tests showed that the gold-containing organelles were devoid of acid phosphatase activity. The generalized rapid spread, retention and selectivity of localization after a single small dose make aurothiomalate a useful marker substance for ultrastructural studies."} {"id": "PMID:1254945", "title": "Transformation of human peripheral lymphocytes by galactose oxidase.", "content": "Human peripheral lymphocytes can be transformed by treatment with galactose oxidase alone. Prior treatment with neuraminidase enhances this effect. The aldehyde blocking agents thiocarbohydrazide, hydroxylamine, dimedone, and sodium borohydride block transformation when they follow, but not when they precede, galactose oxidase treatment. Thus, as is the case for periodate-induced lymphocyte transformation, the formation of free aldehyde at the cell surface would seem to be a critical event in the triggering of transformation by this agent. The degree of transformation is highly variable from individual to individual, and also for the same donor at different times. However, the lymphocytes of some people give a consistently poor response to galactose oxidase. Similar results have been obtained for periodate-induced transformation of human lymphocytes, but to this date this is unexplained.", "contents": "Transformation of human peripheral lymphocytes by galactose oxidase. Human peripheral lymphocytes can be transformed by treatment with galactose oxidase alone. Prior treatment with neuraminidase enhances this effect. The aldehyde blocking agents thiocarbohydrazide, hydroxylamine, dimedone, and sodium borohydride block transformation when they follow, but not when they precede, galactose oxidase treatment. Thus, as is the case for periodate-induced lymphocyte transformation, the formation of free aldehyde at the cell surface would seem to be a critical event in the triggering of transformation by this agent. The degree of transformation is highly variable from individual to individual, and also for the same donor at different times. However, the lymphocytes of some people give a consistently poor response to galactose oxidase. Similar results have been obtained for periodate-induced transformation of human lymphocytes, but to this date this is unexplained."} {"id": "PMID:1254946", "title": "Experimental allergic orchitis and aspermatogenesis. VI. Transfer of allergic orchitis with immune cells.", "content": "Typical experimental allergic orchitis (EAO) and aspermatogenesis were successfully transferred to strain 13 guinea pigs with peritoneal exudate and lymph node cells from male and female donor guinea pigs (lacking detectable antibody) previously sensitized with 9 mug of highly purified GP1 glucoprotein isolated from the sperm acrosome. Attempts to transfer the disease with circulating antibody from hyperimmunized animals were not successful. These studies support a cell-mediated basis for the immunopathologic events in EAO.", "contents": "Experimental allergic orchitis and aspermatogenesis. VI. Transfer of allergic orchitis with immune cells. Typical experimental allergic orchitis (EAO) and aspermatogenesis were successfully transferred to strain 13 guinea pigs with peritoneal exudate and lymph node cells from male and female donor guinea pigs (lacking detectable antibody) previously sensitized with 9 mug of highly purified GP1 glucoprotein isolated from the sperm acrosome. Attempts to transfer the disease with circulating antibody from hyperimmunized animals were not successful. These studies support a cell-mediated basis for the immunopathologic events in EAO."} {"id": "PMID:1254947", "title": "Resistance to murine leukemia in mice rejecting syngeneic somatic hybrid cells.", "content": "(A/J X C3H/HeJ) F1 mice reject somatic cell hybrids of ASL-1 cells (A origin) and LM(TK)- cells (C3H origin), but die from leukemia within 10 days after the inoculation of approximately 10(6) viable ASL-1 cells. Mice rejecting hybrid cells survive for prolonged periods after challenge with otherwise lethal numbers of ASL-1 cells. The hybrid cells, rejected by syngeneic F1 recipients, retained their oncogenic potential as determined by the appearance and progressive growth of tumors in immunologically deficient nu/nu mice injected with the cells. Similar results were obtained using hybrids of a radiation-induced cell line (RADA-1), maintained by serial transfer in strain A mice and LM(TK)- cells. Syngeneic mice injected with RADA-1 X LM(TK)- cells failed to form tumors. Mice rejecting RADA-1 X LM(TK)- hybrid cells survived for prolonged periods after challenge with otherwise lethal numbers of RADA-1 cells.", "contents": "Resistance to murine leukemia in mice rejecting syngeneic somatic hybrid cells. (A/J X C3H/HeJ) F1 mice reject somatic cell hybrids of ASL-1 cells (A origin) and LM(TK)- cells (C3H origin), but die from leukemia within 10 days after the inoculation of approximately 10(6) viable ASL-1 cells. Mice rejecting hybrid cells survive for prolonged periods after challenge with otherwise lethal numbers of ASL-1 cells. The hybrid cells, rejected by syngeneic F1 recipients, retained their oncogenic potential as determined by the appearance and progressive growth of tumors in immunologically deficient nu/nu mice injected with the cells. Similar results were obtained using hybrids of a radiation-induced cell line (RADA-1), maintained by serial transfer in strain A mice and LM(TK)- cells. Syngeneic mice injected with RADA-1 X LM(TK)- cells failed to form tumors. Mice rejecting RADA-1 X LM(TK)- hybrid cells survived for prolonged periods after challenge with otherwise lethal numbers of RADA-1 cells."} {"id": "PMID:1254948", "title": "Production of large amounts of antibodies in individual mice.", "content": "A method is described for the elicitation of substantial amounts of anti-hapten and anti-protein antibodies in ascitic fluids of individual mice of various strains. The method utilizes repeated i.p. inoculations of u.5-mg quantities of antigen in complete Freund's adjuvant. A high volume ratio of adjuvant to antigen solution, and the volume used per inoculation, were shown to be critical factors. Ascitic fluids developed after three to five inoculations and were subsequently tapped repeatedly over a period of several weeks. All strains tested produced substantial amounts of anti-KLH antibodies, but marked differences were noted with respect to response to a hapten. Titers were enhanced in low responders by priming before the induction of ascites. The method is also useful for the production of \"nonspecific\" IgG and other serum components.", "contents": "Production of large amounts of antibodies in individual mice. A method is described for the elicitation of substantial amounts of anti-hapten and anti-protein antibodies in ascitic fluids of individual mice of various strains. The method utilizes repeated i.p. inoculations of u.5-mg quantities of antigen in complete Freund's adjuvant. A high volume ratio of adjuvant to antigen solution, and the volume used per inoculation, were shown to be critical factors. Ascitic fluids developed after three to five inoculations and were subsequently tapped repeatedly over a period of several weeks. All strains tested produced substantial amounts of anti-KLH antibodies, but marked differences were noted with respect to response to a hapten. Titers were enhanced in low responders by priming before the induction of ascites. The method is also useful for the production of \"nonspecific\" IgG and other serum components."} {"id": "PMID:1254949", "title": "Degranulation of basophilic leukocytes in allergic contact dermatitis reactions in man.", "content": "Basophilic leukocytes participating in allergic contact dermatitis in man underwent progressive degranulation over the course of several days after skin test. Less than 10% of basophils were degranulated in 24-hr reactions, but more than 60% were degranulated by 72hr. In electron microscopic individual basophil granules developed looser packing of particles by finely granular material, and eventual loss of all visible granule contents, changes that were progressive between 2- and 3-day reactions.", "contents": "Degranulation of basophilic leukocytes in allergic contact dermatitis reactions in man. Basophilic leukocytes participating in allergic contact dermatitis in man underwent progressive degranulation over the course of several days after skin test. Less than 10% of basophils were degranulated in 24-hr reactions, but more than 60% were degranulated by 72hr. In electron microscopic individual basophil granules developed looser packing of particles by finely granular material, and eventual loss of all visible granule contents, changes that were progressive between 2- and 3-day reactions."} {"id": "PMID:1254950", "title": "Tolerance and contact sensitivity to DNFB in mice. V. Induction of tolerance with DNP compounds and with free and membrane-associated DNFB.", "content": "Immunologic unresponsiveness (tolerance) was induced in a mouse model of contact sensitization to DNFB. The ability to induce tolerance varied with the chemical reactivity of the tolerogen; DNFB was highly tolerogenic, DNBSO3 was moderately tolerogenic, and DNP-lysine was not tolerogenic. Although DNFB is considered a highly reactive compound, tracer studies of injected DNFB showed that it was rapidly excreted. Further studies were therefore done with DNFB attached to mouse erythrocytes. Tolerance to DNFB-RBC was highly specific in vivo; mice tolerant to DNFB showed normal reactivity to TNCB (picryl chloride.) Cells of mice tolerant to DNFB-RBC were also unresponsive to DNBSO3 in vitro. Tolerance to DNFB, DNBSO3, and DNFB-RBC all required time to develop, suggesting that an active process was involved.", "contents": "Tolerance and contact sensitivity to DNFB in mice. V. Induction of tolerance with DNP compounds and with free and membrane-associated DNFB. Immunologic unresponsiveness (tolerance) was induced in a mouse model of contact sensitization to DNFB. The ability to induce tolerance varied with the chemical reactivity of the tolerogen; DNFB was highly tolerogenic, DNBSO3 was moderately tolerogenic, and DNP-lysine was not tolerogenic. Although DNFB is considered a highly reactive compound, tracer studies of injected DNFB showed that it was rapidly excreted. Further studies were therefore done with DNFB attached to mouse erythrocytes. Tolerance to DNFB-RBC was highly specific in vivo; mice tolerant to DNFB showed normal reactivity to TNCB (picryl chloride.) Cells of mice tolerant to DNFB-RBC were also unresponsive to DNBSO3 in vitro. Tolerance to DNFB, DNBSO3, and DNFB-RBC all required time to develop, suggesting that an active process was involved."} {"id": "PMID:1254951", "title": "Tumor-associated blocking factors: isolation from sera of tumor-bearing mice.", "content": "An isolation and partial purifications of tumor-associated blocking factors from the sera of tumor-bearing mice is described. Columns for affinity chromatography were prepared by coupling syngeneic tumor-immune antibodies to Sepharose 4B. Passage of serum through such immunoadsorbent columns removed all blocking activity from tumor-bearers' sera; subsequent elution of the absorbent with 3 M NaSCN recovered the activity. The blocking material was further purified on Sephadex G-200. The data provide evidence for the presence of antigen in tumor-associated blocking factors and are compatible with the hypothesis that blocking factors often consist of antigen and antibodies in the form of immune complexes.", "contents": "Tumor-associated blocking factors: isolation from sera of tumor-bearing mice. An isolation and partial purifications of tumor-associated blocking factors from the sera of tumor-bearing mice is described. Columns for affinity chromatography were prepared by coupling syngeneic tumor-immune antibodies to Sepharose 4B. Passage of serum through such immunoadsorbent columns removed all blocking activity from tumor-bearers' sera; subsequent elution of the absorbent with 3 M NaSCN recovered the activity. The blocking material was further purified on Sephadex G-200. The data provide evidence for the presence of antigen in tumor-associated blocking factors and are compatible with the hypothesis that blocking factors often consist of antigen and antibodies in the form of immune complexes."} {"id": "PMID:1254952", "title": "Genetic control of immune response against random copolymers of glutamic acid and alanine (GA) and tyrosine (GT) in inbred mice.", "content": "An immune response (lr) gene(s) controlling responses to synthetic random copolymers of two amino acids of glutamic acid and alanine (GA) in mice has been well documented. This specific lr gene is linked to the major histocompatibility complex of the species. Mice of the H-2a,b,d,f,k,r and s haplotypes produce high titer antibodies and thus are high responders; whereas mice of the H-2 haplotypes j, ja, p and q produce no detectable antibody and are non responders. The response is \"all or none\" and high response is dominant. Attempts to detect an Ir-GT gene (glutamic acid and tyrosine) after immunization with two GT random copolymers were unsuccessful. However, GT-antibody could be produced after immunization with GT-methylated bovine serum albumin aggregates.", "contents": "Genetic control of immune response against random copolymers of glutamic acid and alanine (GA) and tyrosine (GT) in inbred mice. An immune response (lr) gene(s) controlling responses to synthetic random copolymers of two amino acids of glutamic acid and alanine (GA) in mice has been well documented. This specific lr gene is linked to the major histocompatibility complex of the species. Mice of the H-2a,b,d,f,k,r and s haplotypes produce high titer antibodies and thus are high responders; whereas mice of the H-2 haplotypes j, ja, p and q produce no detectable antibody and are non responders. The response is \"all or none\" and high response is dominant. Attempts to detect an Ir-GT gene (glutamic acid and tyrosine) after immunization with two GT random copolymers were unsuccessful. However, GT-antibody could be produced after immunization with GT-methylated bovine serum albumin aggregates."} {"id": "PMID:1254953", "title": "Development of rat mast cells in vitro. I. Differentiation of mast cells from thymus cells.", "content": "Mast cells were differentiated by long-term culture of rat thymus cells on rat embryonic fibroblasts monolayers. Mature mast cells obtained in the culture were morphologically similar to normal peritoneal and thoracic mast cells and possessed specific receptors for IgE on their surface. In culture, blast cells appeared on the monolayer several days after seeding of thymus cells. These cells developed into young mast cells in the monolayer and became free in the culture medium with maturation. Receptors for IgE were detected on the surface of mastoblasts which contained a small amount of metachromatic granules. Evidence was obtained which suggested that the number and/or affinity of the receptors for IgE increases with maturation of mast cells. It was found that some mast cells differentiated from monolayers of embryo cells without seeding thymus cells. The present experiments, however, clearly showed that mast cells can be differentiated from thymus cell culture without monolayer. It appears that both thymus and embryo tissues contain precursors of mast cells.", "contents": "Development of rat mast cells in vitro. I. Differentiation of mast cells from thymus cells. Mast cells were differentiated by long-term culture of rat thymus cells on rat embryonic fibroblasts monolayers. Mature mast cells obtained in the culture were morphologically similar to normal peritoneal and thoracic mast cells and possessed specific receptors for IgE on their surface. In culture, blast cells appeared on the monolayer several days after seeding of thymus cells. These cells developed into young mast cells in the monolayer and became free in the culture medium with maturation. Receptors for IgE were detected on the surface of mastoblasts which contained a small amount of metachromatic granules. Evidence was obtained which suggested that the number and/or affinity of the receptors for IgE increases with maturation of mast cells. It was found that some mast cells differentiated from monolayers of embryo cells without seeding thymus cells. The present experiments, however, clearly showed that mast cells can be differentiated from thymus cell culture without monolayer. It appears that both thymus and embryo tissues contain precursors of mast cells."} {"id": "PMID:1254954", "title": "Visual detection of carcinoembryonic antigen on surfaces.", "content": "An attempt is made to detect carcinoembryonic antigen (CEA) at clinically interesting concentrations by using a simple immunologic surface test. Antibodies to CEA are detected in a direct test at concentrations below 1 ng/ml. The sensitivity of this assay is mainly limited by diffusion to the reacting surface. CEA is detected in an inhibition test at concentrations down to 20 ng/ml. The sensitivity of this inhibition test is limited by the average equilibrium constant in solution of the antibody-antigen reaction.", "contents": "Visual detection of carcinoembryonic antigen on surfaces. An attempt is made to detect carcinoembryonic antigen (CEA) at clinically interesting concentrations by using a simple immunologic surface test. Antibodies to CEA are detected in a direct test at concentrations below 1 ng/ml. The sensitivity of this assay is mainly limited by diffusion to the reacting surface. CEA is detected in an inhibition test at concentrations down to 20 ng/ml. The sensitivity of this inhibition test is limited by the average equilibrium constant in solution of the antibody-antigen reaction."} {"id": "PMID:1254955", "title": "Regulation of the immune response to tumor antigens. II. The nature of immunosuppressor cells in tumor-bearing hosts.", "content": "Immunosuppressor (IS) cells were found to be generated in tumor-bearing animals (TBA) within 24 hr after inoculation of tumor cells of the methylcholanthrene-induced Sarcoma 1509a and appeared to persist in the hosts as long as the tumor was progressing. However, IS cells disappeared with 5 days after extirpation of the tumor. Increasing doses of thymus cells of TBA increased the degree of suppression of tumor rejection in immune syngeneic animals. Ten million thymus cells of TBA were capable of suppressing significantly the tumor rejection. The IS cells were detected in the thymus, spleens, and draining lymph nodes, as well as in bone marrow of TBA, but could not be detected in the peripheral circulating blood. Since immunosuppressive activity of bone marrow cells from TBA was entirely abolished by the in vitro treatment of the cells with anti-theta serum and complement, the observed immunosuppression appears to be mediated by the T cell population.", "contents": "Regulation of the immune response to tumor antigens. II. The nature of immunosuppressor cells in tumor-bearing hosts. Immunosuppressor (IS) cells were found to be generated in tumor-bearing animals (TBA) within 24 hr after inoculation of tumor cells of the methylcholanthrene-induced Sarcoma 1509a and appeared to persist in the hosts as long as the tumor was progressing. However, IS cells disappeared with 5 days after extirpation of the tumor. Increasing doses of thymus cells of TBA increased the degree of suppression of tumor rejection in immune syngeneic animals. Ten million thymus cells of TBA were capable of suppressing significantly the tumor rejection. The IS cells were detected in the thymus, spleens, and draining lymph nodes, as well as in bone marrow of TBA, but could not be detected in the peripheral circulating blood. Since immunosuppressive activity of bone marrow cells from TBA was entirely abolished by the in vitro treatment of the cells with anti-theta serum and complement, the observed immunosuppression appears to be mediated by the T cell population."} {"id": "PMID:1254956", "title": "Analysis of the humoral immune response to influenza virus in vitro.", "content": "The induction of in vitro primary and secondary humoral immune responses to influenza virus in murine splenic explant culture is described. Anti-influenza antibody synthesized in vitro was detected and quantitated by a radioimmunoassay which utilized influenza coupled to bromoacetylcellulose. Both in vitro primary and secondary responses could be stimulated over a large range of virus doses. In vitro secondary responses were maximal when spleen donors had been immunized by the parenteral route although secondary type responses could be demonstrated as well after primary immunization by pulmonary infection. In vitro stimulation with influenza virus was relatively insensitive to inhibition at high antigen doses. The results are discussed in terms of the response of other antigens in spleen fragment culture.", "contents": "Analysis of the humoral immune response to influenza virus in vitro. The induction of in vitro primary and secondary humoral immune responses to influenza virus in murine splenic explant culture is described. Anti-influenza antibody synthesized in vitro was detected and quantitated by a radioimmunoassay which utilized influenza coupled to bromoacetylcellulose. Both in vitro primary and secondary responses could be stimulated over a large range of virus doses. In vitro secondary responses were maximal when spleen donors had been immunized by the parenteral route although secondary type responses could be demonstrated as well after primary immunization by pulmonary infection. In vitro stimulation with influenza virus was relatively insensitive to inhibition at high antigen doses. The results are discussed in terms of the response of other antigens in spleen fragment culture."} {"id": "PMID:1254957", "title": "Immune serum-mediated cytotoxicity against Trypanosoma rhodesiense.", "content": "The metabolic integrity of Trypanosoma rhodesiense can be assessed in vitro by the extent of incorporation of radiolabeled leucine into trichloroacetic acid precipitable material or into material retained after filtration on a glass fiber filter. Incorporation is an approximately linear function of time, and the rate of incorporation is linearly dependent on cell concentration in the presence of normal rat serum. Incorporation is completely prevented if the organisms are reacted wiith fresh serum from animals immunized with gamma-irradiated parasites; the degree of inhibition is a function of the dose of immune serum used. This serum-mediated cytotoxic activity is abrogated by heating the serum, but can be fully restored by addition of fresh rat or guinea pig serum to the heated immune serum. The serum activity arises promptly after one to four immunizing doses of irradiated parasites, falls to lower levels by 1 month, but persists for at least 2(1/2) months, and is unaffected by challenge with viable trypanosomes.", "contents": "Immune serum-mediated cytotoxicity against Trypanosoma rhodesiense. The metabolic integrity of Trypanosoma rhodesiense can be assessed in vitro by the extent of incorporation of radiolabeled leucine into trichloroacetic acid precipitable material or into material retained after filtration on a glass fiber filter. Incorporation is an approximately linear function of time, and the rate of incorporation is linearly dependent on cell concentration in the presence of normal rat serum. Incorporation is completely prevented if the organisms are reacted wiith fresh serum from animals immunized with gamma-irradiated parasites; the degree of inhibition is a function of the dose of immune serum used. This serum-mediated cytotoxic activity is abrogated by heating the serum, but can be fully restored by addition of fresh rat or guinea pig serum to the heated immune serum. The serum activity arises promptly after one to four immunizing doses of irradiated parasites, falls to lower levels by 1 month, but persists for at least 2(1/2) months, and is unaffected by challenge with viable trypanosomes."} {"id": "PMID:1254958", "title": "Preferential expression of anti-azobenzenearsonate antibodies of heterozygous a1a3 rabbits in the a1 allotype.", "content": "The preferential expression of anti-As antibodies in the allotype a1 of heterozygous a1a3 rabbits immunized with As-TMA-BSA has been investigated by means of quantitative methods. The average content of the anti-As antibodies in a1 and a3 allotypes was 84 and 11%, respectively; the analogous values for anti-TMA antibodies were 41 and 56%, and for anti-BSA antibodies they were 54 and 41%. The molar anti-As/anti-TMA ratios in the heterozygous a1a1 rabbits sensitized with As-TMA-BSA. The very low yields of anti-As-antibodies of allotype a3 cannot be caused by a lack of genes for the production of anti-As antibodies of allotype a3 because a3a3 homozygotes produce considerable amounts of anti-As antibody of allotpye a3. Competition between lymphoid cells having anti-As receptors of different allotype and different affinity for the antigenic p-azobenzenearsonate determinant is discussed as a possible cause for the preferential expression in the a1 allotype.", "contents": "Preferential expression of anti-azobenzenearsonate antibodies of heterozygous a1a3 rabbits in the a1 allotype. The preferential expression of anti-As antibodies in the allotype a1 of heterozygous a1a3 rabbits immunized with As-TMA-BSA has been investigated by means of quantitative methods. The average content of the anti-As antibodies in a1 and a3 allotypes was 84 and 11%, respectively; the analogous values for anti-TMA antibodies were 41 and 56%, and for anti-BSA antibodies they were 54 and 41%. The molar anti-As/anti-TMA ratios in the heterozygous a1a1 rabbits sensitized with As-TMA-BSA. The very low yields of anti-As-antibodies of allotype a3 cannot be caused by a lack of genes for the production of anti-As antibodies of allotype a3 because a3a3 homozygotes produce considerable amounts of anti-As antibody of allotpye a3. Competition between lymphoid cells having anti-As receptors of different allotype and different affinity for the antigenic p-azobenzenearsonate determinant is discussed as a possible cause for the preferential expression in the a1 allotype."} {"id": "PMID:1254959", "title": "Synthesis of Gm allotypes by human tonsillar lymphocytes in culture: concordance with serum phenotype.", "content": "Isolated human tonsillar lymphocytes were cultured with pokeweed mitogen, phytohemagglutinin, and without mitogen for 9 to 28 days. IgK, Gm(a) and Gm(f) were then quantitated in the cell suspensions. In cultures of cells derived from persons whose blood was heterozygous for IgGl allotype antigens Gm(a+f+), approximately equal amounts of Gm(a) and Gm(f) were found. In cultures of cells of Gma or Gmf homozygotes, there was complete concordance between the Gm allotype antigens produced by the cultures and the donor's serum phenotype-with no instance, either at zero time or at culture termination in which a Gm antigen was detected which was absent from the donor's serum. It was concluded that in vitro genetic allotype synthesis in tonsillar lymphocytes during short-term culture mirrored accurately in vivo Gm expression. IgK and Gm antigen synthesis was highest in the flasks containing pokeweed mitogen although both phytohemagglutinin and no-mitogen control flasks showed, in certain experiments, proliferation and an increase in the Ig per viable cell. It was observed that no-mitogen flasks contained twice as much allotype antigen as did phytohemagglutinin flasks suggesting an inhibition of Ig synthesis associated with the mitogen. The tonsillar lymphocytes, under the experimental conditions employed, were shown by a radio-incorporation and immunoprecipitation technique to be synthesizing polyclonal Ig de novo, at the termination of the cultures.", "contents": "Synthesis of Gm allotypes by human tonsillar lymphocytes in culture: concordance with serum phenotype. Isolated human tonsillar lymphocytes were cultured with pokeweed mitogen, phytohemagglutinin, and without mitogen for 9 to 28 days. IgK, Gm(a) and Gm(f) were then quantitated in the cell suspensions. In cultures of cells derived from persons whose blood was heterozygous for IgGl allotype antigens Gm(a+f+), approximately equal amounts of Gm(a) and Gm(f) were found. In cultures of cells of Gma or Gmf homozygotes, there was complete concordance between the Gm allotype antigens produced by the cultures and the donor's serum phenotype-with no instance, either at zero time or at culture termination in which a Gm antigen was detected which was absent from the donor's serum. It was concluded that in vitro genetic allotype synthesis in tonsillar lymphocytes during short-term culture mirrored accurately in vivo Gm expression. IgK and Gm antigen synthesis was highest in the flasks containing pokeweed mitogen although both phytohemagglutinin and no-mitogen control flasks showed, in certain experiments, proliferation and an increase in the Ig per viable cell. It was observed that no-mitogen flasks contained twice as much allotype antigen as did phytohemagglutinin flasks suggesting an inhibition of Ig synthesis associated with the mitogen. The tonsillar lymphocytes, under the experimental conditions employed, were shown by a radio-incorporation and immunoprecipitation technique to be synthesizing polyclonal Ig de novo, at the termination of the cultures."} {"id": "PMID:1254960", "title": "Radioimmunossay for detection of antigen and antibodies to Newcastle disease virus.", "content": "When Newcastle disease virus (NDV) is treated with NP-40 and ether a membrane fraction of 150,000 m.w. is obtained. This fraction which is composed of two polypeptides with m.w. of 56,000 and 76,000 was used in a radioimmunoassay (RIA). The assay was developed for both antigen and antibody and was found to be reproducible, specific, and highly sensitive. Titers of 1:51,200 were determined by RIA as compared to 1:4 by agar gel diffusion and 1:200 by hemaglutination inhibition (HI). As little as 5 ng of viral protein were detected by RIA inhibition technique. Labeled antigen could be stored in the presence of serum, KCI and Triton X-100 at -20 degrees C for as long as 6 weeks and retained similar reactivity as fresh reagent.", "contents": "Radioimmunossay for detection of antigen and antibodies to Newcastle disease virus. When Newcastle disease virus (NDV) is treated with NP-40 and ether a membrane fraction of 150,000 m.w. is obtained. This fraction which is composed of two polypeptides with m.w. of 56,000 and 76,000 was used in a radioimmunoassay (RIA). The assay was developed for both antigen and antibody and was found to be reproducible, specific, and highly sensitive. Titers of 1:51,200 were determined by RIA as compared to 1:4 by agar gel diffusion and 1:200 by hemaglutination inhibition (HI). As little as 5 ng of viral protein were detected by RIA inhibition technique. Labeled antigen could be stored in the presence of serum, KCI and Triton X-100 at -20 degrees C for as long as 6 weeks and retained similar reactivity as fresh reagent."} {"id": "PMID:1254961", "title": "The host antigen phenomenon in experimental murine schistosomiasis. II. Failure to demonstrate destruction of parasites transferred from hamsters to mice.", "content": "Adult Schistosoma monsoni grown in hamsters and transferred directly to the mesenteric vessels of C57BL10J mice previously immunized with hamster cells survive normally despite evidence of cytoxic and hemagglutinating antibodies directed against hamster cells. This finding indicates that species differences may play an important part in the manifestions of the host antigen phenomenon in experimental schistosomiasis.", "contents": "The host antigen phenomenon in experimental murine schistosomiasis. II. Failure to demonstrate destruction of parasites transferred from hamsters to mice. Adult Schistosoma monsoni grown in hamsters and transferred directly to the mesenteric vessels of C57BL10J mice previously immunized with hamster cells survive normally despite evidence of cytoxic and hemagglutinating antibodies directed against hamster cells. This finding indicates that species differences may play an important part in the manifestions of the host antigen phenomenon in experimental schistosomiasis."} {"id": "PMID:1254962", "title": "Gentic control of the immune response to the Ea-2 alloantigen system of the mouse. I. The humoral antibody response.", "content": "The immunization of selected congenic strains and hybrids against the Ea-2.1 cellular alloantigen of the mouse demonstrated that the hammagglutinating antibody response to Ea-2.1 is regulated by a gene or genes associated with the H-2 gene complex. H-2r and H-2b are, respectively, responder and non-responder haplotypes.", "contents": "Gentic control of the immune response to the Ea-2 alloantigen system of the mouse. I. The humoral antibody response. The immunization of selected congenic strains and hybrids against the Ea-2.1 cellular alloantigen of the mouse demonstrated that the hammagglutinating antibody response to Ea-2.1 is regulated by a gene or genes associated with the H-2 gene complex. H-2r and H-2b are, respectively, responder and non-responder haplotypes."} {"id": "PMID:1254963", "title": "A phosphorylcholine idiotype related to TEPC 15 in mice infected with Ascaris suum.", "content": "A serum component, binding antigens having phosphorylcholine (PC) determinants were induced in several strains of mice by infection with Ascaris suum. This component was isolated and demonstrated to be an IgM (K) anti-PC antibody having idiotypic determinants in common with the IgA PC-binding myeloma protein TEPC 15. Rabbit anti-idiotypic antisera prepared with this component had idiotypic specificity for TEPC 15 and cross-idiotypic recognition of MOPC 167 and McPC 603, all IgA PC-binding myeloma proteins. The antisera also recognized determinants not present on TEPC 15. IgM and idiotype levels were quantitated by radial immunodiffusion and PC-specific antibody measured by hemagglutination (HA) with sheep erythrocytes coated with pneumococcal-C-polysaccharide. Mean IgM levels ranged from 2.5 to 8.7 mg/ml, idiotype from 0.54 to 5.3 mg/ml; and HA titers from 1:512 to 1:130,000 in different mouse strains. The high PC-specific antibody response was not duplicated by immunization with dead ascaris larvae or by infection with two other nematode species.", "contents": "A phosphorylcholine idiotype related to TEPC 15 in mice infected with Ascaris suum. A serum component, binding antigens having phosphorylcholine (PC) determinants were induced in several strains of mice by infection with Ascaris suum. This component was isolated and demonstrated to be an IgM (K) anti-PC antibody having idiotypic determinants in common with the IgA PC-binding myeloma protein TEPC 15. Rabbit anti-idiotypic antisera prepared with this component had idiotypic specificity for TEPC 15 and cross-idiotypic recognition of MOPC 167 and McPC 603, all IgA PC-binding myeloma proteins. The antisera also recognized determinants not present on TEPC 15. IgM and idiotype levels were quantitated by radial immunodiffusion and PC-specific antibody measured by hemagglutination (HA) with sheep erythrocytes coated with pneumococcal-C-polysaccharide. Mean IgM levels ranged from 2.5 to 8.7 mg/ml, idiotype from 0.54 to 5.3 mg/ml; and HA titers from 1:512 to 1:130,000 in different mouse strains. The high PC-specific antibody response was not duplicated by immunization with dead ascaris larvae or by infection with two other nematode species."} {"id": "PMID:1254964", "title": "Amyloid fibril protein AA: purification and properties of the antigenically related serum component as determined by solid phase radioimmunoassay.", "content": "The isolation by gel filtration of a serum component (SAA), antigenically related to the major filbrillar amyloid protein (AA), associated with \"secondary\" amyloidosis, has been monitored by a solid phase radioimmunoassay for the AA protein to detect cross-reacting serum fractions. Evidence is presented that not all cross-reacting antigenic determinants are accessible in native SAA, since additional determinants are revealed during the isolation procedure. The native structure of SAA appears to be quite labile. SAA from freshly collected serum has a m.w. of 180,000 and co-chromatographs with IgG. However, species of higher m.w. are observed after storage of serum at 4 degrees C or upon chromatography of serum in ammonium bicarbonate. Denatured SAA has a tendency to aggregate under strong dissociating conditions. A 12.500 m.w. antigenic species (SAAL) was detected upon guanidine-HCl denaturation of SAA, by earlier studies employing double immunodiffusion. However, evidence is presented here that the major part of the antigenic acitivity after guanidine-HCl treatment was of m.w. greater than 12,500, but was unreactive in double immunodiffusion. Formic acid treatment of cross-reacting serum fractions does result in virtually complete dissociation of SAA to SAAL, however. Furthermore, Formic acid-dissociated SAAL is of comparable immunoreactivity with AA, on a molar basis, unlike SAAL obtained from SAA by guanidine-HCl denaturation.", "contents": "Amyloid fibril protein AA: purification and properties of the antigenically related serum component as determined by solid phase radioimmunoassay. The isolation by gel filtration of a serum component (SAA), antigenically related to the major filbrillar amyloid protein (AA), associated with \"secondary\" amyloidosis, has been monitored by a solid phase radioimmunoassay for the AA protein to detect cross-reacting serum fractions. Evidence is presented that not all cross-reacting antigenic determinants are accessible in native SAA, since additional determinants are revealed during the isolation procedure. The native structure of SAA appears to be quite labile. SAA from freshly collected serum has a m.w. of 180,000 and co-chromatographs with IgG. However, species of higher m.w. are observed after storage of serum at 4 degrees C or upon chromatography of serum in ammonium bicarbonate. Denatured SAA has a tendency to aggregate under strong dissociating conditions. A 12.500 m.w. antigenic species (SAAL) was detected upon guanidine-HCl denaturation of SAA, by earlier studies employing double immunodiffusion. However, evidence is presented here that the major part of the antigenic acitivity after guanidine-HCl treatment was of m.w. greater than 12,500, but was unreactive in double immunodiffusion. Formic acid treatment of cross-reacting serum fractions does result in virtually complete dissociation of SAA to SAAL, however. Furthermore, Formic acid-dissociated SAAL is of comparable immunoreactivity with AA, on a molar basis, unlike SAAL obtained from SAA by guanidine-HCl denaturation."} {"id": "PMID:1254965", "title": "The indiction by complement of a change in KSCN-dissociable red cell membrane lipids.", "content": "During complement lysis of antibody-sensitized sheep erythrocytes (EA) there was a larger loss of membrane phospholipids than during lysis elicited by hypotonic buffer. In addition, membranes prepared from complement-lysed EA had a marked reduction in KSCN (2.4 M)-dissociable membrane cholesterol and phospholipids, as compared to membranes from EA lysed hypotonically. Complement lysis caused a mild reduction in the amount of KSCN-dissociable membrane hexose but no change in the amount of dissociable protein. The impairment in dissociation of membrane lipids was related to the action of C8; it did not occur with membranes from EA that were treated with heat-inactivated (56 degrees C for 30 min) human serum, C4-deficient guinea pig serum, C6-deficient rabbit serum, or the first seven human complement components. EA lysed with limited amounts of complement exhibited a partial impairment in KSCN-dissociable lipids. Membranes from erythrocytes lysed with melittin showed a large increase in dissociation by KSCN of lipids, proteins,and hexoses. Membranes from erythocytes lysed with lysolecithin or phospholipase C showed, in addition to a reduction in dissociable lipid, a much larger reduction in dissociable hexose than a membranes from complement-lysed cells. These profiles of reactivity with 2.4 M KSCN inidcate that the membrane pertubations caused caused by complement may be specific. We conclude that complement-lysis is accompanied by a major rearrangement of membrane cholesterol and phospholipid which could be demonstrated in membranes from cells lysed by only one or very few complement lesions. Therefore, it appears that the lesions induce a propragated change in the lipid organization which extends throughout large areas of the membrane. This change might be responsible for the impairment of membrane permeability that follows the action of complement and results in cell destruction.", "contents": "The indiction by complement of a change in KSCN-dissociable red cell membrane lipids. During complement lysis of antibody-sensitized sheep erythrocytes (EA) there was a larger loss of membrane phospholipids than during lysis elicited by hypotonic buffer. In addition, membranes prepared from complement-lysed EA had a marked reduction in KSCN (2.4 M)-dissociable membrane cholesterol and phospholipids, as compared to membranes from EA lysed hypotonically. Complement lysis caused a mild reduction in the amount of KSCN-dissociable membrane hexose but no change in the amount of dissociable protein. The impairment in dissociation of membrane lipids was related to the action of C8; it did not occur with membranes from EA that were treated with heat-inactivated (56 degrees C for 30 min) human serum, C4-deficient guinea pig serum, C6-deficient rabbit serum, or the first seven human complement components. EA lysed with limited amounts of complement exhibited a partial impairment in KSCN-dissociable lipids. Membranes from erythrocytes lysed with melittin showed a large increase in dissociation by KSCN of lipids, proteins,and hexoses. Membranes from erythocytes lysed with lysolecithin or phospholipase C showed, in addition to a reduction in dissociable lipid, a much larger reduction in dissociable hexose than a membranes from complement-lysed cells. These profiles of reactivity with 2.4 M KSCN inidcate that the membrane pertubations caused caused by complement may be specific. We conclude that complement-lysis is accompanied by a major rearrangement of membrane cholesterol and phospholipid which could be demonstrated in membranes from cells lysed by only one or very few complement lesions. Therefore, it appears that the lesions induce a propragated change in the lipid organization which extends throughout large areas of the membrane. This change might be responsible for the impairment of membrane permeability that follows the action of complement and results in cell destruction."} {"id": "PMID:1254966", "title": "Temporary inhibition of antibody-dependent, cell-mediated cytotoxicity by pretreatment of human attacking cells with ammonium chloride.", "content": "Treatment of lymphoid cell preparations with ammonium chloride buffers to remove contaminating erythroid cells markedly reduced the ability of these cells to function as attacking cells in antibody dependent cell mediated cytotoxicity tests (ADCC). The lymphoid cells, however, retained their ability to adhere to antibody-coated target cells. Recovery of function 20 hr after exposure to ammonium chloride suggests a metabolic rather than receptor effect of these salts on the ADCC function of lymphocytes.", "contents": "Temporary inhibition of antibody-dependent, cell-mediated cytotoxicity by pretreatment of human attacking cells with ammonium chloride. Treatment of lymphoid cell preparations with ammonium chloride buffers to remove contaminating erythroid cells markedly reduced the ability of these cells to function as attacking cells in antibody dependent cell mediated cytotoxicity tests (ADCC). The lymphoid cells, however, retained their ability to adhere to antibody-coated target cells. Recovery of function 20 hr after exposure to ammonium chloride suggests a metabolic rather than receptor effect of these salts on the ADCC function of lymphocytes."} {"id": "PMID:1254967", "title": "Cell membrane IgD: demonstration of IgD on human lymphocytes by enzyme-catalyzed iodination and comparison with cell surface Ig of mouse, guinea pig, and rabbit.", "content": "A substantial fraction of human cord blood and peripheral blood lymphocytes have recently been shown to bear IgD. Although IgD has not been identified in mice, it has been suggested that it is also a major surface immunoglobulin of murine lymphocytes. Thus, lactoperoxidase-catalyzed iodination of surface immunoglobulin of mouse spleen and lymph node cells reveals the existence of an IgH chain differing from mu, gamma, and alpha-chain both antigenically and by mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This new H chain class has been previously proposed to be the mouse homologue of delta-chain. In this paper, we analyzed human, mouse, guinea pig, and rabbit lymphoid cell membrane Ig by lactoperoxidase-catalyzed iodination, extraction with non-ionic detergent precipitation with a variety of specific anti-Ig sera, and electrophoresis of dissolved reduced precipitates on sodium dodecyl sulfate-polyacrylamide gels. Our studies confirm the previous reports of a new mouse cell membrane H chain with a mobility more rapid than that of mu-chain. However, we fail to detect a molecule with this electrophoretic mobility on the surface of guinea pig or rabbit lymph node and spleen cells. Moreover, neither anti-kappa nor anti-delta antibody precipitates a molecule with an H chain of this mobility from labeled extracts of human cord blood or peripheral blood lymphocytes. Cell surface delta was identified on both human cord blood and peripheral blood lymphocytes, but it proved to have mobility similar to human and mouse mu-chain. This result indicates either that mouse delta-chain has an electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels which differs appreciably from that of human membrane delta-chain or that the newly described mouse H chain is not the homologue of human delta-chain.", "contents": "Cell membrane IgD: demonstration of IgD on human lymphocytes by enzyme-catalyzed iodination and comparison with cell surface Ig of mouse, guinea pig, and rabbit. A substantial fraction of human cord blood and peripheral blood lymphocytes have recently been shown to bear IgD. Although IgD has not been identified in mice, it has been suggested that it is also a major surface immunoglobulin of murine lymphocytes. Thus, lactoperoxidase-catalyzed iodination of surface immunoglobulin of mouse spleen and lymph node cells reveals the existence of an IgH chain differing from mu, gamma, and alpha-chain both antigenically and by mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This new H chain class has been previously proposed to be the mouse homologue of delta-chain. In this paper, we analyzed human, mouse, guinea pig, and rabbit lymphoid cell membrane Ig by lactoperoxidase-catalyzed iodination, extraction with non-ionic detergent precipitation with a variety of specific anti-Ig sera, and electrophoresis of dissolved reduced precipitates on sodium dodecyl sulfate-polyacrylamide gels. Our studies confirm the previous reports of a new mouse cell membrane H chain with a mobility more rapid than that of mu-chain. However, we fail to detect a molecule with this electrophoretic mobility on the surface of guinea pig or rabbit lymph node and spleen cells. Moreover, neither anti-kappa nor anti-delta antibody precipitates a molecule with an H chain of this mobility from labeled extracts of human cord blood or peripheral blood lymphocytes. Cell surface delta was identified on both human cord blood and peripheral blood lymphocytes, but it proved to have mobility similar to human and mouse mu-chain. This result indicates either that mouse delta-chain has an electrophoretic mobility on sodium dodecyl sulfate-polyacrylamide gels which differs appreciably from that of human membrane delta-chain or that the newly described mouse H chain is not the homologue of human delta-chain."} {"id": "PMID:1254969", "title": "Antibody-dependent cell-mediated cytotoxicity in humans. III. Effect of protease inhibitors and substrates.", "content": "Different classes of protease inhibitors and substrates were tested for their effect on the ability of human lymphocytes to mediate antibody-dependent cytotoxicity (Ab CMC). All the inhibitors tested (serine esterase inhibitors, chloromethyl ketone derivatives of tosyl-amino acids, synthetic protease substrates), except for the naturally occurring protease inhibitors (derived from soybean, lima bean, and porcine pancreas), were able to suppress, or to reduce insignificantly, the cytotoxicity. In the absence of a direct demonstration of an esterase activity, sensitive to the action of the inhibitors in the effector lymphocytes, careful controls were used to restrict the possibility that some nonspecific effect of the drugs was being interpreted. Particularly, the dependence of the inhibition of cytotoxicity as an effect of drugs on membrane transport mechanisms or on energy metabolism was excluded. The similarity between results obtained with compounds of different chemical characteristics and different molecular mechanisms of action supports a specific effect of the inhibitor on cellular esterase(s) or possibly protease(s). The fully reversible inhibition obtained with serine esterase inhibitors suggests that the relevant enzymes are activated only after effector-target cell interaction; the irreversible effect of chloromethyl ketone derivatives, however, does not allow the participation of already activated enzymes to be excluded. The results presented in this study on the probable role of cellular esterases, on cation requirement and on the sequence of biochemical steps in Ab CMC add a new element to the analogy between this cellular phenomenon and different types of cytotoxicity or other immunologically induced cellular reactions, suggesting that the biochemical mechanisms of cytotoxicity may partly reflect a common pattern of cellular response to external stimuli.", "contents": "Antibody-dependent cell-mediated cytotoxicity in humans. III. Effect of protease inhibitors and substrates. Different classes of protease inhibitors and substrates were tested for their effect on the ability of human lymphocytes to mediate antibody-dependent cytotoxicity (Ab CMC). All the inhibitors tested (serine esterase inhibitors, chloromethyl ketone derivatives of tosyl-amino acids, synthetic protease substrates), except for the naturally occurring protease inhibitors (derived from soybean, lima bean, and porcine pancreas), were able to suppress, or to reduce insignificantly, the cytotoxicity. In the absence of a direct demonstration of an esterase activity, sensitive to the action of the inhibitors in the effector lymphocytes, careful controls were used to restrict the possibility that some nonspecific effect of the drugs was being interpreted. Particularly, the dependence of the inhibition of cytotoxicity as an effect of drugs on membrane transport mechanisms or on energy metabolism was excluded. The similarity between results obtained with compounds of different chemical characteristics and different molecular mechanisms of action supports a specific effect of the inhibitor on cellular esterase(s) or possibly protease(s). The fully reversible inhibition obtained with serine esterase inhibitors suggests that the relevant enzymes are activated only after effector-target cell interaction; the irreversible effect of chloromethyl ketone derivatives, however, does not allow the participation of already activated enzymes to be excluded. The results presented in this study on the probable role of cellular esterases, on cation requirement and on the sequence of biochemical steps in Ab CMC add a new element to the analogy between this cellular phenomenon and different types of cytotoxicity or other immunologically induced cellular reactions, suggesting that the biochemical mechanisms of cytotoxicity may partly reflect a common pattern of cellular response to external stimuli."} {"id": "PMID:1254970", "title": "Neutrophil receptors for IgG and complement: their roles in the attachment and ingestion phases of phagocytosis.", "content": "The functional roles of IgG and C3b in phagocytosis by human peripheral neutrophils were investigated. Phagocytosis of Staphylococcus aureus in the presence of human serum was severely depressed by heat inactivation of serum at 56 degrees C for 30 min. Experiments with varying particle: leukocyte ratios in the presence of complement-inactivated sera showed that particle-bound C3b can mediate a 10-fold enhancement of the overall phagocytic rate. When sheep erythrocytes were sensitized with either IgG or IgM, only the former were bound to and readily internalized by neutrophils. Erythrocytes sensitized with both IgM and C3b were bound but not internalized. Furthermore, the presence of Fc fragments during incubation of S. aureus or latex beads with neutrophils in the presence of IgG or fresh serum affected a total inhibition of internalization but did not significantly alter adherence. Quantitative data regarding IgG sensitization indicated that bound C3b results in at least a 3-fold decrease in the amount of sensitizing IgG required for 50% maximal phagocytic response by neutrophils. On the basis of the above results, it is argued that particle-bound C3b functions primarily in the adherence phase and that bound IgG serves as a trigger for the internalization phase of phagocytosis.", "contents": "Neutrophil receptors for IgG and complement: their roles in the attachment and ingestion phases of phagocytosis. The functional roles of IgG and C3b in phagocytosis by human peripheral neutrophils were investigated. Phagocytosis of Staphylococcus aureus in the presence of human serum was severely depressed by heat inactivation of serum at 56 degrees C for 30 min. Experiments with varying particle: leukocyte ratios in the presence of complement-inactivated sera showed that particle-bound C3b can mediate a 10-fold enhancement of the overall phagocytic rate. When sheep erythrocytes were sensitized with either IgG or IgM, only the former were bound to and readily internalized by neutrophils. Erythrocytes sensitized with both IgM and C3b were bound but not internalized. Furthermore, the presence of Fc fragments during incubation of S. aureus or latex beads with neutrophils in the presence of IgG or fresh serum affected a total inhibition of internalization but did not significantly alter adherence. Quantitative data regarding IgG sensitization indicated that bound C3b results in at least a 3-fold decrease in the amount of sensitizing IgG required for 50% maximal phagocytic response by neutrophils. On the basis of the above results, it is argued that particle-bound C3b functions primarily in the adherence phase and that bound IgG serves as a trigger for the internalization phase of phagocytosis."} {"id": "PMID:1254971", "title": "Separate Fc-receptors for immunoglogulins IgG2a and IgG2b on an established cell line of mouse macrophages.", "content": "The specificity of Fe-receptors on IC-21 cells, an established line of mouse peritoneal macrophages with antibody-dependent effector cell activity has been examined. Only IgG2a and IgG2b myeloma proteins bound readily to IC-21 Fc-receptors, the former in nonaggregated as well as aggregated form, the latter only as aggregated complexes. Thus, IgG2a bound in a manner characteristic of classically defined cytophilic antibody, whereas the binding of IgG2b appeared to be mediated by Fc-receptors for antigen-antibody complexes. Evidence is presented in support of the view that IC-21 macrophages possess separate and distinct Fc-receptor sites for these two immunoglobulins.", "contents": "Separate Fc-receptors for immunoglogulins IgG2a and IgG2b on an established cell line of mouse macrophages. The specificity of Fe-receptors on IC-21 cells, an established line of mouse peritoneal macrophages with antibody-dependent effector cell activity has been examined. Only IgG2a and IgG2b myeloma proteins bound readily to IC-21 Fc-receptors, the former in nonaggregated as well as aggregated form, the latter only as aggregated complexes. Thus, IgG2a bound in a manner characteristic of classically defined cytophilic antibody, whereas the binding of IgG2b appeared to be mediated by Fc-receptors for antigen-antibody complexes. Evidence is presented in support of the view that IC-21 macrophages possess separate and distinct Fc-receptor sites for these two immunoglobulins."} {"id": "PMID:1254972", "title": "In vitro hemolysis of autologous erythrocytes caused by immune murine spleen cells and spherules of the fungus Coccidioides immitis.", "content": "This communication describes an in vitro system wherein mouse erythrocytes are lysed in the presence of spherules of the fungus Coccidioides immitis and spleen cells from syngeneic mice immunized with a variety of antigens. The antigens include: tobacco mosaic virus in complete Freund's adjuvant (CFA), CFA alone, separate components of CFA, sheep erythrocytes, and allogeneic tumor. Spleen cells from mice sublethally infected with C. immitis are also capable of participating in this response. The lytic phenomenon, which does not require complement, is dependent upon the number of spleen cells per culture, the number of spherules per culture, the time of culture incubation, the amount of antigen injected into the animal and the time after immunization at which spleen cells are recovered. Live spherules or spherules killed with heat, with dimethylsulfoxide, or with formalin were effective participants, together with immune spleen cells, in the lytic reaction.", "contents": "In vitro hemolysis of autologous erythrocytes caused by immune murine spleen cells and spherules of the fungus Coccidioides immitis. This communication describes an in vitro system wherein mouse erythrocytes are lysed in the presence of spherules of the fungus Coccidioides immitis and spleen cells from syngeneic mice immunized with a variety of antigens. The antigens include: tobacco mosaic virus in complete Freund's adjuvant (CFA), CFA alone, separate components of CFA, sheep erythrocytes, and allogeneic tumor. Spleen cells from mice sublethally infected with C. immitis are also capable of participating in this response. The lytic phenomenon, which does not require complement, is dependent upon the number of spleen cells per culture, the number of spherules per culture, the time of culture incubation, the amount of antigen injected into the animal and the time after immunization at which spleen cells are recovered. Live spherules or spherules killed with heat, with dimethylsulfoxide, or with formalin were effective participants, together with immune spleen cells, in the lytic reaction."} {"id": "PMID:1254973", "title": "Age-associated involution of cellular immune function. I. Accelerated decline of mitogen reactivity of spleen cells in adult thymectomized mice.", "content": "Autoimmune-susceptible (A/J and C57BL/6J) and nonautoimmune-susceptible (DBA/1J) strains of mice were adult thymectomized (aTx). Groups of mice treated by aTx, aTx and 330 rads (R), aTx and 650 R, and 330 R OR 650 R only, were compared to normal age-matched control (normal and sham Tx) mice. T cell functions were then followed as measured by in vitro spleen cell responsiveness to the T cell mitogens phytohemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) in a long-term study. A decline in spleen cell responsiveness with natural aging up to 18 months of age was seen to PHA in all three strains and to SEB in A/J and C57BL/J mice. Adult Tx alone was followed by an accelerated decline in spleen cell responsiveness to PHA and SEB in all three strains of mice. Irradiation combined with aTx-reduced spleen cell responsiveness to SEB in A/J and DBA/1J mice. Irradiation with or without aTx diminished the bone marrow stem cell pool as measured by exogenous colony-forming units, and the hematocrit of all three strains of mice. Thus, the natural decline in cellular immunity with aging was accelerated by aTx in both autoimmune-susceptible and non-autoimmune-susceptible strains of mice. These results emphasize that physiologic thymic function(s) must continue throughout life in order to maintain T cell function.", "contents": "Age-associated involution of cellular immune function. I. Accelerated decline of mitogen reactivity of spleen cells in adult thymectomized mice. Autoimmune-susceptible (A/J and C57BL/6J) and nonautoimmune-susceptible (DBA/1J) strains of mice were adult thymectomized (aTx). Groups of mice treated by aTx, aTx and 330 rads (R), aTx and 650 R, and 330 R OR 650 R only, were compared to normal age-matched control (normal and sham Tx) mice. T cell functions were then followed as measured by in vitro spleen cell responsiveness to the T cell mitogens phytohemagglutinin (PHA) and staphylococcal enterotoxin B (SEB) in a long-term study. A decline in spleen cell responsiveness with natural aging up to 18 months of age was seen to PHA in all three strains and to SEB in A/J and C57BL/J mice. Adult Tx alone was followed by an accelerated decline in spleen cell responsiveness to PHA and SEB in all three strains of mice. Irradiation combined with aTx-reduced spleen cell responsiveness to SEB in A/J and DBA/1J mice. Irradiation with or without aTx diminished the bone marrow stem cell pool as measured by exogenous colony-forming units, and the hematocrit of all three strains of mice. Thus, the natural decline in cellular immunity with aging was accelerated by aTx in both autoimmune-susceptible and non-autoimmune-susceptible strains of mice. These results emphasize that physiologic thymic function(s) must continue throughout life in order to maintain T cell function."} {"id": "PMID:1254974", "title": "The chromic chloride method of coupling antigens to erythrocytes: definition of some important parameters.", "content": "Factors affecting the efficiency of the chronic cloride method of coupling antigen to erythrocytes were studied using a radioactive tracer. The amount of chromic chloride required for optimal coupling was related to the concentration of protein in the reaction mixture. Coupling was considerably more efficient when the chromic chloride solution was allowed to 'age' prior to use. In the system studied, the addition of piperazine buffer made little difference to the degree of coupling. The reaction was shown to proceed very rapidly. 50% of the final uptake of antigen took place within seconds, and the reaction was essentially complete 5 min after initiation. The importance of adequate mixing during the addition of the chromic chloride solution was emphasised.", "contents": "The chromic chloride method of coupling antigens to erythrocytes: definition of some important parameters. Factors affecting the efficiency of the chronic cloride method of coupling antigen to erythrocytes were studied using a radioactive tracer. The amount of chromic chloride required for optimal coupling was related to the concentration of protein in the reaction mixture. Coupling was considerably more efficient when the chromic chloride solution was allowed to 'age' prior to use. In the system studied, the addition of piperazine buffer made little difference to the degree of coupling. The reaction was shown to proceed very rapidly. 50% of the final uptake of antigen took place within seconds, and the reaction was essentially complete 5 min after initiation. The importance of adequate mixing during the addition of the chromic chloride solution was emphasised."} {"id": "PMID:1254975", "title": "Reliability of the enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of Trichinella spiralis infections in conventionally raised pigs.", "content": "An enzyme immunoassay with horse radish peroxidase as marker enzyme for detection of antibodies to Trichinella spiralis in pigs is described. In the enzyme-linked immunosorbent assay (ELISA) quantitation of specific antibodies is obtained by means of peroxidase labeled anti-species-immunoglobulin in antigen-coated tubes. The enzyme remaining in the tube after washing provides a measure of the amount of specific antibodies in the serum. A crude saline extract of T. spiralis muscle larvae served as antigen, 5 mug protein/ml being a satisfactory concentration. Lyophilization of antigen had no adverse effect on sensitivity. To decrease background staining the use of an optimal conjugate dilution was important. Adding bovine serum albumen to the conjugate was essential to decrease background reactions. Suitable substrate incubation times were studied. Washing was performed with tap water and Tween 20. In experiments with conventionally raised slaughter pigs infected with different numbers of T. spiralis larvae a positive correlation was found between initial dose of larvae and amount of antibodies detected by ELISA. Compared with immunofluorescence (IF) ELISA was more sensitive. IF yielded positive results in 11 out of 34 infected animals, whereas ELISA results were positive in 27. To evaluate ELISA under practical conditions extinction values of sera from infected and non-infected conventional pigs were compared with the highest extinction value in a group of 74 negative conventional pig sera. The relatively high background reaction of some of these negative sera decreased the number of positive practical ELISA results from 27 to 19 out of 34. In 1 out of 10 non-infected animals a false positive practical ELISA result was obtained.", "contents": "Reliability of the enzyme-linked immunosorbent assay (ELISA) for the serodiagnosis of Trichinella spiralis infections in conventionally raised pigs. An enzyme immunoassay with horse radish peroxidase as marker enzyme for detection of antibodies to Trichinella spiralis in pigs is described. In the enzyme-linked immunosorbent assay (ELISA) quantitation of specific antibodies is obtained by means of peroxidase labeled anti-species-immunoglobulin in antigen-coated tubes. The enzyme remaining in the tube after washing provides a measure of the amount of specific antibodies in the serum. A crude saline extract of T. spiralis muscle larvae served as antigen, 5 mug protein/ml being a satisfactory concentration. Lyophilization of antigen had no adverse effect on sensitivity. To decrease background staining the use of an optimal conjugate dilution was important. Adding bovine serum albumen to the conjugate was essential to decrease background reactions. Suitable substrate incubation times were studied. Washing was performed with tap water and Tween 20. In experiments with conventionally raised slaughter pigs infected with different numbers of T. spiralis larvae a positive correlation was found between initial dose of larvae and amount of antibodies detected by ELISA. Compared with immunofluorescence (IF) ELISA was more sensitive. IF yielded positive results in 11 out of 34 infected animals, whereas ELISA results were positive in 27. To evaluate ELISA under practical conditions extinction values of sera from infected and non-infected conventional pigs were compared with the highest extinction value in a group of 74 negative conventional pig sera. The relatively high background reaction of some of these negative sera decreased the number of positive practical ELISA results from 27 to 19 out of 34. In 1 out of 10 non-infected animals a false positive practical ELISA result was obtained."} {"id": "PMID:1254976", "title": "Lymphocyte activation. VIII. The application of a whole blood test to the quantitative analysis of PHA responsive T cells.", "content": "In diluted blood predominantly T cells responded to purified PHA (pure leucoagglutinin Wellcome). Red cells and non-T mononuclear cells increased PHA responsiveness of T cells at concentrations present in the peripheral blood. Addition of polymorphonuclear leucocytes was a very slight further advantage. The incorporation of [3H] thymidine reflected the numbers of T cells in culture, although not perfectly linearly, since counts increased when more T cells were added to the cultures. It was therefore concluded that in cultures of diluted whole blood non-specific amplification mechanisms were provided and responses reflected the performance of stimulated T lymphocytes. Since the method is simple and the number of technical variables is relatively small, it is possible to establish a \"normal\" range of PHA responsiveness expressed in absolute counts per minute, and thus directly compare results from different laboratories.", "contents": "Lymphocyte activation. VIII. The application of a whole blood test to the quantitative analysis of PHA responsive T cells. In diluted blood predominantly T cells responded to purified PHA (pure leucoagglutinin Wellcome). Red cells and non-T mononuclear cells increased PHA responsiveness of T cells at concentrations present in the peripheral blood. Addition of polymorphonuclear leucocytes was a very slight further advantage. The incorporation of [3H] thymidine reflected the numbers of T cells in culture, although not perfectly linearly, since counts increased when more T cells were added to the cultures. It was therefore concluded that in cultures of diluted whole blood non-specific amplification mechanisms were provided and responses reflected the performance of stimulated T lymphocytes. Since the method is simple and the number of technical variables is relatively small, it is possible to establish a \"normal\" range of PHA responsiveness expressed in absolute counts per minute, and thus directly compare results from different laboratories."} {"id": "PMID:1254977", "title": "A new screening method for adenosine deaminase and nucleoside phosphorylase.", "content": "An improved screening test for both adenosine deaminase and nucleoside phosphorylase is described.", "contents": "A new screening method for adenosine deaminase and nucleoside phosphorylase. An improved screening test for both adenosine deaminase and nucleoside phosphorylase is described."} {"id": "PMID:1254987", "title": "Persistence of neuroadapted mumps virus in brains of newborn hamsters after intraperitoneal inoculation.", "content": "Neuroadapted mumps virus produces systemic infection in newborn hamsters after intraperitoneal inoculation. Virus is disseminated via a low-level viremia and appears to enter the central nervous system by passage through the choroid plexus. At such sites, choroidal and ependymal epithelial cells are productively infected and become a source for further viral spread throughout the brain parenchyma. The development of neutralizing and hemagglutination-inhibiting antibodies in serum correlates with the clearance of virus from most systemic sites. However, peristence of virus in both brain and kidney is demonstrated late in this infection.", "contents": "Persistence of neuroadapted mumps virus in brains of newborn hamsters after intraperitoneal inoculation. Neuroadapted mumps virus produces systemic infection in newborn hamsters after intraperitoneal inoculation. Virus is disseminated via a low-level viremia and appears to enter the central nervous system by passage through the choroid plexus. At such sites, choroidal and ependymal epithelial cells are productively infected and become a source for further viral spread throughout the brain parenchyma. The development of neutralizing and hemagglutination-inhibiting antibodies in serum correlates with the clearance of virus from most systemic sites. However, peristence of virus in both brain and kidney is demonstrated late in this infection."} {"id": "PMID:1254988", "title": "Activity of combinations of antimicrobial agents against Bacteroides fragilis.", "content": "Thirty-two clinical isolates of Bacteroides fragilis were tested against nine pairs of antimicrobial agents by means of an agar dilution technique. A synergistic effect was observed with the combination of clindamycin and metronidazole. End points were achieved with 17 strains. Of these strains, 13 (76%) were inhibited by the combination of clindamycin and metronidazole; each drug was present at a concentration of less than or equal to 25% of its minimal inhibitory concentration when tested alone. This combination also showed synergistic bactericidal activity against three of six strains examined by a tube dilution technique. No antagonism was noted with any strain. The other eight combinations tested failed to show a consistent synergistic effect, although no antagonism was observed. These in vitro data indicate that antagonism is not likely to be encountered when combination therapy is used for B. fragilis infections. For selected B. fragilis infections, the combination of clindamycin and metronidazole may be useful.", "contents": "Activity of combinations of antimicrobial agents against Bacteroides fragilis. Thirty-two clinical isolates of Bacteroides fragilis were tested against nine pairs of antimicrobial agents by means of an agar dilution technique. A synergistic effect was observed with the combination of clindamycin and metronidazole. End points were achieved with 17 strains. Of these strains, 13 (76%) were inhibited by the combination of clindamycin and metronidazole; each drug was present at a concentration of less than or equal to 25% of its minimal inhibitory concentration when tested alone. This combination also showed synergistic bactericidal activity against three of six strains examined by a tube dilution technique. No antagonism was noted with any strain. The other eight combinations tested failed to show a consistent synergistic effect, although no antagonism was observed. These in vitro data indicate that antagonism is not likely to be encountered when combination therapy is used for B. fragilis infections. For selected B. fragilis infections, the combination of clindamycin and metronidazole may be useful."} {"id": "PMID:1254989", "title": "Relation of infection with Neisseria gonorrhoeae to ABO blood groups.", "content": "The relation of infection with Neisseria gonorrhoeae to the blood groups A, B, AB, and O was examined in 584 women attending a prenatal clinic. The occurrence of gonorrhea was significantly higher in black patients with blood group B than in those with blood groups A, AB, or O.", "contents": "Relation of infection with Neisseria gonorrhoeae to ABO blood groups. The relation of infection with Neisseria gonorrhoeae to the blood groups A, B, AB, and O was examined in 584 women attending a prenatal clinic. The occurrence of gonorrhea was significantly higher in black patients with blood group B than in those with blood groups A, AB, or O."} {"id": "PMID:1254990", "title": "Equal susceptibility of males and females on Santa Cruz Island to the carrier state of hepatitis B surface antigen.", "content": "Various studies have shown that hepatitis B surface antigen is detected more frequently in the blood of asymptomatic males than in that of asymptomatic females. The reason for this difference might be that males are more frequently infected than females or that males more frequently become asymptomatic carriers when they are infected. The sex distribution of hepatitis B surface antigen and antibody, as measured by reversed passive hemagglutination and passive hemagglutination, was determined in a Melanesian population. The frequency of the antigen was higher among males, but the ratio of antigen to antibody was the same in both sexes. This finding indicated that the higher frequency in males was due to a higher rate of infection rather than to a greater susceptibility of the males to the chronic carrier state.", "contents": "Equal susceptibility of males and females on Santa Cruz Island to the carrier state of hepatitis B surface antigen. Various studies have shown that hepatitis B surface antigen is detected more frequently in the blood of asymptomatic males than in that of asymptomatic females. The reason for this difference might be that males are more frequently infected than females or that males more frequently become asymptomatic carriers when they are infected. The sex distribution of hepatitis B surface antigen and antibody, as measured by reversed passive hemagglutination and passive hemagglutination, was determined in a Melanesian population. The frequency of the antigen was higher among males, but the ratio of antigen to antibody was the same in both sexes. This finding indicated that the higher frequency in males was due to a higher rate of infection rather than to a greater susceptibility of the males to the chronic carrier state."} {"id": "PMID:1254991", "title": "Biological properties of the M-44 strain of Coxiella burneti.", "content": "The attenuated M-44 strain of Coxiella burneti was investigated for biological characteristics affecting its use as a live vaccine. After 25 serial passages in guinea pigs, the strain did not develop phase I properties detectable by the microagglutination test. Infectious organisms were not detected in untreated guinea pigs later than 12 weeks after inoculation; however, infection could be reactivated at later times by the production of stress (by pregnancy or drug treatment) in guinea pigs that had recovered. Evidence of reactivated infection was observed in recovered pregnant animals just before parturition at 46 weeks after infection, in methyl prednisolone-treated animals at 56 weeks, and in cyclophosphamide-treated guinea pigs at 96 weeks. A low rate of intercage and intracage infection was recorded.", "contents": "Biological properties of the M-44 strain of Coxiella burneti. The attenuated M-44 strain of Coxiella burneti was investigated for biological characteristics affecting its use as a live vaccine. After 25 serial passages in guinea pigs, the strain did not develop phase I properties detectable by the microagglutination test. Infectious organisms were not detected in untreated guinea pigs later than 12 weeks after inoculation; however, infection could be reactivated at later times by the production of stress (by pregnancy or drug treatment) in guinea pigs that had recovered. Evidence of reactivated infection was observed in recovered pregnant animals just before parturition at 46 weeks after infection, in methyl prednisolone-treated animals at 56 weeks, and in cyclophosphamide-treated guinea pigs at 96 weeks. A low rate of intercage and intracage infection was recorded."} {"id": "PMID:1254995", "title": "Chemical characterization of the structure of cholera toxin and its natural toxoid.", "content": "Acrylamide gel electrophoresis demonstrated that the toxin of Vibrio cholerae is comprised of three polypeptide chains, alpha, beta, and gamma, of molecular weights 24,000, 9,700, and 9,700 daltons, respectively. Amino acid sequence analysis of intact toxin indicated a molecular composition of alpha gamma beta4. Acrylamide gel electrophoresis and sequence analysis confirmed that the natural toxoid (choleragenoid) is identical to the toxin beta-chain. The alpha- and gamma-chains of the toxin are disulfide-linked (fragment A) but are noncovalently bound to the beta-chains. About 50% of the primary structure of the N-terminal portion of the beta-chain has been identified and a small segment of the D-terminus has also been characterized. Twenty residues of the N-terminal portions of the alpha- and gamma-chains have been tentativly identified. The amino acid composition of the beta-chain was determined and compared to that of the natural toxoid.", "contents": "Chemical characterization of the structure of cholera toxin and its natural toxoid. Acrylamide gel electrophoresis demonstrated that the toxin of Vibrio cholerae is comprised of three polypeptide chains, alpha, beta, and gamma, of molecular weights 24,000, 9,700, and 9,700 daltons, respectively. Amino acid sequence analysis of intact toxin indicated a molecular composition of alpha gamma beta4. Acrylamide gel electrophoresis and sequence analysis confirmed that the natural toxoid (choleragenoid) is identical to the toxin beta-chain. The alpha- and gamma-chains of the toxin are disulfide-linked (fragment A) but are noncovalently bound to the beta-chains. About 50% of the primary structure of the N-terminal portion of the beta-chain has been identified and a small segment of the D-terminus has also been characterized. Twenty residues of the N-terminal portions of the alpha- and gamma-chains have been tentativly identified. The amino acid composition of the beta-chain was determined and compared to that of the natural toxoid."} {"id": "PMID:1254996", "title": "Aspects of the interaction of Vibrio cholerae toxin with the pigeon red cell membrane.", "content": "The ganglioside galactosy-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide (GM1) is readily accumulated in pigeon red cell membranes soaked with [3H]GM1 (1-100 mug/ml) at 37 C for 30 min. This treatment enhances the activation of adenyl cyclase by the toxin of Vibrio cholerae. An attempt was made at correlation of the amount of incorporated GM1 with the increased binding of toxin and activation of adenyl cyclase. Cells with less than 2 mug of incorporated GM1 per 4 X 10(9) cells bind 5-10 mug more toxin than do untreated cells, which bind 0.25 mug per 4 X 10(9) cells. Cells with more than 2 mug of GM1 bound (per 4 X 10(9) CELls) which has been incorporated from micellar solutions of GM1 (greater than 20 mug/ml), do not bind any more extra toxin. In untreated cells, 0.1 mug of toxin is involved in the activation of adenyl cyclase. In GM1-treated cells 0.25-0.5 mug of toxin is involved, although at least 5 mug of toxin is bound. It is concluded that 90% of the extra toxin-binding sites on the GM1-treated cell are nonproductive.", "contents": "Aspects of the interaction of Vibrio cholerae toxin with the pigeon red cell membrane. The ganglioside galactosy-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide (GM1) is readily accumulated in pigeon red cell membranes soaked with [3H]GM1 (1-100 mug/ml) at 37 C for 30 min. This treatment enhances the activation of adenyl cyclase by the toxin of Vibrio cholerae. An attempt was made at correlation of the amount of incorporated GM1 with the increased binding of toxin and activation of adenyl cyclase. Cells with less than 2 mug of incorporated GM1 per 4 X 10(9) cells bind 5-10 mug more toxin than do untreated cells, which bind 0.25 mug per 4 X 10(9) cells. Cells with more than 2 mug of GM1 bound (per 4 X 10(9) CELls) which has been incorporated from micellar solutions of GM1 (greater than 20 mug/ml), do not bind any more extra toxin. In untreated cells, 0.1 mug of toxin is involved in the activation of adenyl cyclase. In GM1-treated cells 0.25-0.5 mug of toxin is involved, although at least 5 mug of toxin is bound. It is concluded that 90% of the extra toxin-binding sites on the GM1-treated cell are nonproductive."} {"id": "PMID:1254997", "title": "Stimulation of adenylate cyclase by Vibrio cholerae toxin and its active subunit.", "content": "The mechanism by which Vibrio cholerae toxin and its active subunit A stimulate adenylate cyclase of rat liver plasma membrane after in vivo or in vitro exposure was investigated. Stimulation of adenylate cyclase was more efficient with cholera toxin than with subunit A in whole animals and in \"soluble\" preparations of adenylate cyclase. Toxin-stimulated plasma membrane adenylate cyclase activity persisted after solubilization from the membrane by detergent, while subunit A stimulation was destroyed by detergent treatment. Detergent-free \"soluble\" enzyme could be stimulated in vitro by cholera toxin, but such stimulation by subunit A was very weak. Binding studies with iodotoxin or iodosubunit A confirmed that the interaction of toxin with adenylate cyclase in \"soluble\" preparations could be the result of specific binding to the enzyme. The uncertainty as to whether G M1 ganglioside (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide; GGnSLC) is present in these fractions limited the interpretation of the data on binding. A biological modification of subunit A prior to the activation of adenylate cyclase is inferred from these data.", "contents": "Stimulation of adenylate cyclase by Vibrio cholerae toxin and its active subunit. The mechanism by which Vibrio cholerae toxin and its active subunit A stimulate adenylate cyclase of rat liver plasma membrane after in vivo or in vitro exposure was investigated. Stimulation of adenylate cyclase was more efficient with cholera toxin than with subunit A in whole animals and in \"soluble\" preparations of adenylate cyclase. Toxin-stimulated plasma membrane adenylate cyclase activity persisted after solubilization from the membrane by detergent, while subunit A stimulation was destroyed by detergent treatment. Detergent-free \"soluble\" enzyme could be stimulated in vitro by cholera toxin, but such stimulation by subunit A was very weak. Binding studies with iodotoxin or iodosubunit A confirmed that the interaction of toxin with adenylate cyclase in \"soluble\" preparations could be the result of specific binding to the enzyme. The uncertainty as to whether G M1 ganglioside (galactosyl-N-acetylgalactosaminyl [sialosyl] lactosyl ceramide; GGnSLC) is present in these fractions limited the interpretation of the data on binding. A biological modification of subunit A prior to the activation of adenylate cyclase is inferred from these data."} {"id": "PMID:1255009", "title": "Aspiration biopsy. An aid in the diagnosis of para-nasal tumours.", "content": "Three cases are reported to demonstrate (1) the difficulty in diagnosing the nature of nasopharyngeal tumours (2) the assistance given by the fine-needle aspiration biopsy technique in cases of paranasal tumours. Reliance should not be placed on this technique alone. It should be performed at the initial examination together with conventional techniques. In this way, the patient may be spared the need for multiple anaesthetics and a diagnosis may be arrived at more promptly so that treatment may be instituted more quickly.", "contents": "Aspiration biopsy. An aid in the diagnosis of para-nasal tumours. Three cases are reported to demonstrate (1) the difficulty in diagnosing the nature of nasopharyngeal tumours (2) the assistance given by the fine-needle aspiration biopsy technique in cases of paranasal tumours. Reliance should not be placed on this technique alone. It should be performed at the initial examination together with conventional techniques. In this way, the patient may be spared the need for multiple anaesthetics and a diagnosis may be arrived at more promptly so that treatment may be instituted more quickly."} {"id": "PMID:1255010", "title": "Massive acquired cholesteatoma of the temporal bone.", "content": "Nine patients with massive acquired cholesteatoma of the temporal bone were treated by radical mastoidectomy, facial nerve decompression, and excision of the inner ear. The commonest presenting symptoms were otorrhea and deafness, but otalgia, vertigo, external swelling and facial nerve palsies were also seen. Polytomography was helpful in assessing the degree of bone erosion preoperatively. The large cavity present following cholesteatoma excision was partially obliterated by a superiorly based temporalis muscle pedicle which helped to seal the internal auditory meatus and prevented the development of a cerebral hernia. Those patients with preoperative facial nerve palsies showed evidence of nerve degeneration and had incomplete recovery at a one year follow-up.", "contents": "Massive acquired cholesteatoma of the temporal bone. Nine patients with massive acquired cholesteatoma of the temporal bone were treated by radical mastoidectomy, facial nerve decompression, and excision of the inner ear. The commonest presenting symptoms were otorrhea and deafness, but otalgia, vertigo, external swelling and facial nerve palsies were also seen. Polytomography was helpful in assessing the degree of bone erosion preoperatively. The large cavity present following cholesteatoma excision was partially obliterated by a superiorly based temporalis muscle pedicle which helped to seal the internal auditory meatus and prevented the development of a cerebral hernia. Those patients with preoperative facial nerve palsies showed evidence of nerve degeneration and had incomplete recovery at a one year follow-up."} {"id": "PMID:1255011", "title": "Acid-base equilibrium in Meni\u00e8re's disease.", "content": "57 patients suffering from Meiere's disease have been examined: metabolic alkalosis has been found in 39 and metabolic acidosis in 4. Electrolytes (Na, K and Cl) were normal. Among the 31 subjects in the control series a slight metabolic alkalosis qas detected only twice. Follow-up of several patients, from one to three years, resulted in a realization of a parallel between metabolic disturbance and Meniere symptoms. A provocation test, by sodium bicarbonate oral administration, has beem attempted twice: in both instances alkalosis did increase strongly but, only once, vertigo was elicited. Meniere patients found in alkalosis were given acidifying drugs to normalize their acid-base equilibrium. Such treatment proved effective in preventing acute cochleo-vestibular crises and in improving tinnitus and deafness (in the fluctuating stage). On the interruption of treatment symptoms reappeared. The physiological-pathological significance of metabolic alkalosis in Meniere's disease still remains unclear and, consequently, this can be considered merely a predisposing factor in endolymphatic hydrops.", "contents": "Acid-base equilibrium in Meni\u00e8re's disease. 57 patients suffering from Meiere's disease have been examined: metabolic alkalosis has been found in 39 and metabolic acidosis in 4. Electrolytes (Na, K and Cl) were normal. Among the 31 subjects in the control series a slight metabolic alkalosis qas detected only twice. Follow-up of several patients, from one to three years, resulted in a realization of a parallel between metabolic disturbance and Meniere symptoms. A provocation test, by sodium bicarbonate oral administration, has beem attempted twice: in both instances alkalosis did increase strongly but, only once, vertigo was elicited. Meniere patients found in alkalosis were given acidifying drugs to normalize their acid-base equilibrium. Such treatment proved effective in preventing acute cochleo-vestibular crises and in improving tinnitus and deafness (in the fluctuating stage). On the interruption of treatment symptoms reappeared. The physiological-pathological significance of metabolic alkalosis in Meniere's disease still remains unclear and, consequently, this can be considered merely a predisposing factor in endolymphatic hydrops."} {"id": "PMID:1255013", "title": "Benign cartilagenous tumour of the temporomandibular joint.", "content": "An unusual case of a benign cartilagenous tumour of the temporomandibular joint is presented. The difficulties encountered in histological diagnosis, the benign behaviour of the tumour and the need for restraint in treatment are emphasized.", "contents": "Benign cartilagenous tumour of the temporomandibular joint. An unusual case of a benign cartilagenous tumour of the temporomandibular joint is presented. The difficulties encountered in histological diagnosis, the benign behaviour of the tumour and the need for restraint in treatment are emphasized."} {"id": "PMID:1255014", "title": "Carotid body tumour. Exicsion with resection of carotid arteries.", "content": "A case of carotid body tumour is reported and the salient features of its histopathology have been described. Its excision with resection of the carotid arteries can be safely undertaken if the tumour is of long duration, the angiography shows marked displacement of the carotid arteries and if the blood pressure is maintained during surgery by regulating the blood transfusion and lowering the head end of the patient, thereby preventing fatal brain hypoxia. The fact that it is a potentially malignant and radioresistant tumour, makes its excision with or without ligation of the carotid arteries almost imperative.", "contents": "Carotid body tumour. Exicsion with resection of carotid arteries. A case of carotid body tumour is reported and the salient features of its histopathology have been described. Its excision with resection of the carotid arteries can be safely undertaken if the tumour is of long duration, the angiography shows marked displacement of the carotid arteries and if the blood pressure is maintained during surgery by regulating the blood transfusion and lowering the head end of the patient, thereby preventing fatal brain hypoxia. The fact that it is a potentially malignant and radioresistant tumour, makes its excision with or without ligation of the carotid arteries almost imperative."} {"id": "PMID:1255015", "title": "Unilateral blindness following vidian neurectomy.", "content": "A case with unilateral blindness is being reported, to arouse awareness in surgeons about the possibility of such a serious complication after Vidian neurectomy by the trans-septal route.", "contents": "Unilateral blindness following vidian neurectomy. A case with unilateral blindness is being reported, to arouse awareness in surgeons about the possibility of such a serious complication after Vidian neurectomy by the trans-septal route."} {"id": "PMID:1255016", "title": "11, 15, 19-trihydroxy-9-ketoprost-13-enoic acid and 11, 15, 19-trihydroxy-9-ketoprosta-5, 13-dienoic acid in human seminal fluid.", "content": "Two novel prostaglandins (PG) have been found in human seminal fluid which had been frozen immediately after collection. They were characterized by combined gas-liquid chromatography-mass spectrometry of various derivatives as 19-hydroxy prostaglandin E1 (11, 15, 19-trihydroxy-9-ketoprost-13-enoic acid) and 19-hydroxy prostaglandin E2 (11, 15, 19-trihydroxy-9-ketoprosta-5, 13-dienoic acid). They were present in three to five times the quantity of prostaglandins E1 and E2. Incubation of seminal fluid for 3 hr at 25 degrees C reduced levels of 190H-PGEs2.5-fold and PGE22-fold, while increasing levels of PGAs and PGBs 2-fold. No 190H PGA or 190H PGB was detected in extracts of unincubated fluid. The PGAs, PGBs and their 19-hydroxy analogs are probably artifacts arising metabolically or as a result of classical isolation techniques.", "contents": "11, 15, 19-trihydroxy-9-ketoprost-13-enoic acid and 11, 15, 19-trihydroxy-9-ketoprosta-5, 13-dienoic acid in human seminal fluid. Two novel prostaglandins (PG) have been found in human seminal fluid which had been frozen immediately after collection. They were characterized by combined gas-liquid chromatography-mass spectrometry of various derivatives as 19-hydroxy prostaglandin E1 (11, 15, 19-trihydroxy-9-ketoprost-13-enoic acid) and 19-hydroxy prostaglandin E2 (11, 15, 19-trihydroxy-9-ketoprosta-5, 13-dienoic acid). They were present in three to five times the quantity of prostaglandins E1 and E2. Incubation of seminal fluid for 3 hr at 25 degrees C reduced levels of 190H-PGEs2.5-fold and PGE22-fold, while increasing levels of PGAs and PGBs 2-fold. No 190H PGA or 190H PGB was detected in extracts of unincubated fluid. The PGAs, PGBs and their 19-hydroxy analogs are probably artifacts arising metabolically or as a result of classical isolation techniques."} {"id": "PMID:1255017", "title": "Bile acids. XLIX. Allocholic acid, the major bile acid of Uromastix hardwickii.", "content": "Tauroallocholate is the major bile salt of the lizard, Uromastix hardwickii. Alkaline hydrolysis of bile from 25 gallbladders provided 1.21 g of acidic material, about 90% of which was allocholic acid. Analyses by gas-liquid chromatography, and mass spectrometry verified the presence of almost 10% of deoxycholic acid and smaller amounts of other 5alpha and 5beta-bile acids.", "contents": "Bile acids. XLIX. Allocholic acid, the major bile acid of Uromastix hardwickii. Tauroallocholate is the major bile salt of the lizard, Uromastix hardwickii. Alkaline hydrolysis of bile from 25 gallbladders provided 1.21 g of acidic material, about 90% of which was allocholic acid. Analyses by gas-liquid chromatography, and mass spectrometry verified the presence of almost 10% of deoxycholic acid and smaller amounts of other 5alpha and 5beta-bile acids."} {"id": "PMID:1255018", "title": "Measurement of human high density lipoprotein apolipoprotein A-1 in serum by radioimmunoassay.", "content": "A sensitive and specific double antibody radioimmunoassay for the major apolipoprotein (apo A-I) of human serum high density lipoprotein (HDL) was developed. Initial studies indicated that direct measurements of apo A-I concentration in whole untreated sera or isolated high density lipoprotein fractions yielded variable results, which were lower than those obtained in the corresponding samples which had been subjected to delipidation. Subsequently, it was observed that heating diluted sera or HDL for 3 hr at 52 degrees C prior to assay resulted in maximal increases in apo A-I immunoreactivity to levels comparable to those found in the delipidated specimens. This simple procedure permitted multiple sera to be assayed efficiently with full recovery of apo A-I.", "contents": "Measurement of human high density lipoprotein apolipoprotein A-1 in serum by radioimmunoassay. A sensitive and specific double antibody radioimmunoassay for the major apolipoprotein (apo A-I) of human serum high density lipoprotein (HDL) was developed. Initial studies indicated that direct measurements of apo A-I concentration in whole untreated sera or isolated high density lipoprotein fractions yielded variable results, which were lower than those obtained in the corresponding samples which had been subjected to delipidation. Subsequently, it was observed that heating diluted sera or HDL for 3 hr at 52 degrees C prior to assay resulted in maximal increases in apo A-I immunoreactivity to levels comparable to those found in the delipidated specimens. This simple procedure permitted multiple sera to be assayed efficiently with full recovery of apo A-I."} {"id": "PMID:1255019", "title": "Measurement of squalene in human tissues and plasma: validation and application.", "content": "A method is described for accurate and reproducible measurement of squalene in plasma, feces, urine, bile, and tissue that depends on isolation by alumina column chromatography after mild saponification and on measurement by gas-liquid chromatography. Recoveries from all tissues exceeded 80% and from plasma 96%; losses were accurately corrected by appropriate additions of squalene as an overall recovery standard.", "contents": "Measurement of squalene in human tissues and plasma: validation and application. A method is described for accurate and reproducible measurement of squalene in plasma, feces, urine, bile, and tissue that depends on isolation by alumina column chromatography after mild saponification and on measurement by gas-liquid chromatography. Recoveries from all tissues exceeded 80% and from plasma 96%; losses were accurately corrected by appropriate additions of squalene as an overall recovery standard."} {"id": "PMID:1255020", "title": "Effect of p-chlorophenoxyisobutyrate on the antilipolytic action of insulin and insulin binding in isolated adipocytes.", "content": "The present study was undertaken to investigate the potentiation by p-chlorophenoxyisobutyrate (CPIB) of the antilipolytic effect of insulin in isolated adipocytes from rats fed a (1) sucrose diet, (2) glycerol-lard diet, or (3) chow diet. CPIB supplementation in the diet consistently resulted in decreased serum triglyceride levels in rats from the three dietary groups. The catecholamine-stimulated glycerol release was significantly depressed to a greater extent by insulin when the fat cells were obtained from rats given CPIB compared to those without drug treatment. The enhanced insulin sensitivity was, however, not accompanied by any changes in insulin binding to adipocytes. These two observations were found in cell preparations from rats fed any one of the diets, although differences among dietary groups could be detected. In an in vitro experiment, epinephrine-stimulated glycerol release was progressively inhibited by increasing concentrations of CPIB in the incubation medium. However, the antilipolytic response to an optimal concentration of insulin (100 muU/ml) was augmented in the presence of CPIB. Thus, it seems that CPIB can potentiate the action of insulin in inhibiting mobilization of free fatty acid from the adipose tissue, and the coordinated effect of both antilipolytic agents is important in lowering serum triglyceride concentration. The mechanism by which CPIB facilitates the effect of insulin is discussed.", "contents": "Effect of p-chlorophenoxyisobutyrate on the antilipolytic action of insulin and insulin binding in isolated adipocytes. The present study was undertaken to investigate the potentiation by p-chlorophenoxyisobutyrate (CPIB) of the antilipolytic effect of insulin in isolated adipocytes from rats fed a (1) sucrose diet, (2) glycerol-lard diet, or (3) chow diet. CPIB supplementation in the diet consistently resulted in decreased serum triglyceride levels in rats from the three dietary groups. The catecholamine-stimulated glycerol release was significantly depressed to a greater extent by insulin when the fat cells were obtained from rats given CPIB compared to those without drug treatment. The enhanced insulin sensitivity was, however, not accompanied by any changes in insulin binding to adipocytes. These two observations were found in cell preparations from rats fed any one of the diets, although differences among dietary groups could be detected. In an in vitro experiment, epinephrine-stimulated glycerol release was progressively inhibited by increasing concentrations of CPIB in the incubation medium. However, the antilipolytic response to an optimal concentration of insulin (100 muU/ml) was augmented in the presence of CPIB. Thus, it seems that CPIB can potentiate the action of insulin in inhibiting mobilization of free fatty acid from the adipose tissue, and the coordinated effect of both antilipolytic agents is important in lowering serum triglyceride concentration. The mechanism by which CPIB facilitates the effect of insulin is discussed."} {"id": "PMID:1255021", "title": "Duvatrienediols in cuticular wax of Burley tobacco leaves.", "content": "4, 8, 13-Duvatriene-1, 3-diol diastereoisomers have been identified in the cuticular wax of fresh Burley tobacco leaves. Their structures were determined by gas-liquid chromatography, mass spectrometry, and infrared and ultraviolet spectroscopy. Butylboronic acid derivatives of the alpha, beta-isomers were separated by gas-liquid chromatography and identified by mass spectrometry. The quantitative determination by gas-liquid chromatography revealed that the duvatrienediols are major components in the cuticular wax of Nicotiana tabacum. The duvatrienediol content in young leaves is higher than in old leaves, and in young leaves this compound may account for half of the cuticular wax.", "contents": "Duvatrienediols in cuticular wax of Burley tobacco leaves. 4, 8, 13-Duvatriene-1, 3-diol diastereoisomers have been identified in the cuticular wax of fresh Burley tobacco leaves. Their structures were determined by gas-liquid chromatography, mass spectrometry, and infrared and ultraviolet spectroscopy. Butylboronic acid derivatives of the alpha, beta-isomers were separated by gas-liquid chromatography and identified by mass spectrometry. The quantitative determination by gas-liquid chromatography revealed that the duvatrienediols are major components in the cuticular wax of Nicotiana tabacum. The duvatrienediol content in young leaves is higher than in old leaves, and in young leaves this compound may account for half of the cuticular wax."} {"id": "PMID:1255022", "title": "Synthesis of 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol and 5beta-cholestane-3alpha, 7alpha, 245, 25-pentol.", "content": "This paper describes syntheses of 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol and 5beta-cholestane-3alpha, 7alpha, 12alpha, 24xi, 25-pentol which give higher yields than previously published methods. In addition, 5beta-cholestane-3alpha, 7alpha, 12alpha, 24xi, 25-pentol was synthesized by a different procedure, namely via performic acid oxidation of the correspinding unsaturated triol, which gave a lower yield but avoided the formation of 5beta-cholestane-3alpha, 7alpha, 12alpha, 25, 26-pentol, which normally tends to contaminate the final product. Structures were confirmed by gas-liquid chromatography, infrared-, proton magnetic resonance- and mass spectrometry, 5beta-Cholestane-3alpha, 7alpha, 12alpha, 25-tetrol and 5beta-cholestane-3alpha, 7alpha, 12alpha, 24xi, 25-pentol were required for in vivo and in vitro studies of the (hypothetical) 25-hydroxylation pathway of cholic acid biosynthesis.", "contents": "Synthesis of 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol and 5beta-cholestane-3alpha, 7alpha, 245, 25-pentol. This paper describes syntheses of 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol and 5beta-cholestane-3alpha, 7alpha, 12alpha, 24xi, 25-pentol which give higher yields than previously published methods. In addition, 5beta-cholestane-3alpha, 7alpha, 12alpha, 24xi, 25-pentol was synthesized by a different procedure, namely via performic acid oxidation of the correspinding unsaturated triol, which gave a lower yield but avoided the formation of 5beta-cholestane-3alpha, 7alpha, 12alpha, 25, 26-pentol, which normally tends to contaminate the final product. Structures were confirmed by gas-liquid chromatography, infrared-, proton magnetic resonance- and mass spectrometry, 5beta-Cholestane-3alpha, 7alpha, 12alpha, 25-tetrol and 5beta-cholestane-3alpha, 7alpha, 12alpha, 24xi, 25-pentol were required for in vivo and in vitro studies of the (hypothetical) 25-hydroxylation pathway of cholic acid biosynthesis."} {"id": "PMID:1255023", "title": "A sterospecific synthesis of 7alpha-hydroxycholesterol.", "content": "The five step synthesis of 7alpha-hydroxycholesterol utilizes the solvolysis of 7alpha-bromocholesterol benzoate with potassium acetate in acetic acid as the key step in controlling the stereospecificity of the reaction sequence. This reaction yields 7alpha-acetoxycholesterol benzoate with retention of configuration at position seven. The diester is readily reduced with lithium aluminum to 7alpha-hydroxycholesterol.", "contents": "A sterospecific synthesis of 7alpha-hydroxycholesterol. The five step synthesis of 7alpha-hydroxycholesterol utilizes the solvolysis of 7alpha-bromocholesterol benzoate with potassium acetate in acetic acid as the key step in controlling the stereospecificity of the reaction sequence. This reaction yields 7alpha-acetoxycholesterol benzoate with retention of configuration at position seven. The diester is readily reduced with lithium aluminum to 7alpha-hydroxycholesterol."} {"id": "PMID:1255037", "title": "Measurement of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma during the perinatal period.", "content": "A method is described for the resolution and individual quantitation of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma. The steroids were extracted by solvent partition and separated by LH-20 Sephadex column chromatography. Radioimmunoassay was used for the measurement of 11-deoxycortisol and cortisone and competitive protein-binding for corticosterone and cortisol. The relative levels of these steroids in the plasma of chronically catheterized sheep foetuses from 12 days before birth to term and then in the newborn lamb until 2 days of age are recorded. Cortisol gradually increased from a basal concentration of between 0 - 5 and 3 - 0 mug/100 ml plasma between days 12 and 5 pre partum, and then rose rapidly to 10 mug/100 ml plasma during the last 5 days of pregnancy to reach a maximum during or just after birth. Two days post partum the levels had fallen to approximately 3 mug/100 ml plasma. The mean value for 11-deoxycortisol between days 8 and 3 pre partum was 0 - 4 mug/100 ml plasma and increased in the final days before delivery to 1 - 0 mug/100 ml. Corticosterone initially showed slightly higher levels (approximately 1 - 5 mug/100 ml) in the earlier period of investigation but then fell during the immediate pre-partum period to 0 - 8 mug/100 ml. Cortisone was not detected at any stage of the investigations. The relationship between levels of cortisol and 11-deoxycortisol in foetal plasma and myometrial contractility is shown. An increase in uterine activity was seen to occur at the time that cortisol levels were at their maximum. The 11-deoxycortisol values throughout this particular study remained low. The results are discussed in relation to recorded levels in the adult and to previous studies in vitro with regard to changing steroid biosynthetic enzyme activity.", "contents": "Measurement of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma during the perinatal period. A method is described for the resolution and individual quantitation of cortisol, cortisone, 11-deoxycortisol and corticosterone in foetal sheep plasma. The steroids were extracted by solvent partition and separated by LH-20 Sephadex column chromatography. Radioimmunoassay was used for the measurement of 11-deoxycortisol and cortisone and competitive protein-binding for corticosterone and cortisol. The relative levels of these steroids in the plasma of chronically catheterized sheep foetuses from 12 days before birth to term and then in the newborn lamb until 2 days of age are recorded. Cortisol gradually increased from a basal concentration of between 0 - 5 and 3 - 0 mug/100 ml plasma between days 12 and 5 pre partum, and then rose rapidly to 10 mug/100 ml plasma during the last 5 days of pregnancy to reach a maximum during or just after birth. Two days post partum the levels had fallen to approximately 3 mug/100 ml plasma. The mean value for 11-deoxycortisol between days 8 and 3 pre partum was 0 - 4 mug/100 ml plasma and increased in the final days before delivery to 1 - 0 mug/100 ml. Corticosterone initially showed slightly higher levels (approximately 1 - 5 mug/100 ml) in the earlier period of investigation but then fell during the immediate pre-partum period to 0 - 8 mug/100 ml. Cortisone was not detected at any stage of the investigations. The relationship between levels of cortisol and 11-deoxycortisol in foetal plasma and myometrial contractility is shown. An increase in uterine activity was seen to occur at the time that cortisol levels were at their maximum. The 11-deoxycortisol values throughout this particular study remained low. The results are discussed in relation to recorded levels in the adult and to previous studies in vitro with regard to changing steroid biosynthetic enzyme activity."} {"id": "PMID:1255038", "title": "Hormone storage in individual neurosecretory granules of the pituitary gland: A quantitative ultrastructural approach to hormone storage in the neural lobe.", "content": "A quantitative ultrastructural study of the neurosecretory granules in the neural lobe of the rat was performed in order to calculate the number of such granules in the neural lobe and thus, provided all hormone is intragranular, to derive the hormone content of individual granules. The results suggest that the gland contains 1 - 44 X 10(10) granules and that an individual granule (mean diameter 160 nm) contains about 84000 hormone molecules. The errors involved in the many measurements made are analysed, and the calculated value for the amount of space available for each hormone molecule within the granule is shown to agree well with independently reported data for the expected size of a molecule of protein-hormone complex, and for the size of subunits visualized in freeze-etched material. These results are compatible with exclusive intragranular hormone storage as a 'solid' core, and the physical form that this core might take is discussed. The data are used to express what is known of hormone turnover and release in terms of the numbers of granules involved. Comparison of different parts of the neural lobe suggests that, apart from the most anterior part of the gland, there is little regional variation in quantitative aspects of granule storage in the neural lobe.", "contents": "Hormone storage in individual neurosecretory granules of the pituitary gland: A quantitative ultrastructural approach to hormone storage in the neural lobe. A quantitative ultrastructural study of the neurosecretory granules in the neural lobe of the rat was performed in order to calculate the number of such granules in the neural lobe and thus, provided all hormone is intragranular, to derive the hormone content of individual granules. The results suggest that the gland contains 1 - 44 X 10(10) granules and that an individual granule (mean diameter 160 nm) contains about 84000 hormone molecules. The errors involved in the many measurements made are analysed, and the calculated value for the amount of space available for each hormone molecule within the granule is shown to agree well with independently reported data for the expected size of a molecule of protein-hormone complex, and for the size of subunits visualized in freeze-etched material. These results are compatible with exclusive intragranular hormone storage as a 'solid' core, and the physical form that this core might take is discussed. The data are used to express what is known of hormone turnover and release in terms of the numbers of granules involved. Comparison of different parts of the neural lobe suggests that, apart from the most anterior part of the gland, there is little regional variation in quantitative aspects of granule storage in the neural lobe."} {"id": "PMID:1255039", "title": "Distribution of neurosecretory granules among the anatomical compartments of the neurosecretory processes of the pituitary gland: a quantitative ultrastructural approach to hormone storage in the neural lobe.", "content": "The distribution of neurosecretory granules in various anatomical compartments of neurosecretory axons of the neural lobe of the rat pituitary has been studied. Apart from the most anterior tip of the gland, where granules are largely restricted to undilated axons and a few 'swellings', the proportional compartmental storage of granules is essentially homogeneous for the rest of the gland: 13% of granules are found in undilated axons, 31% in axonal 'endings' (which contain microvesicles and abut the basement membrane) and 55% in axonal 'swellings' (which are devoid of significant numbers of microvesicles). These values indicate that the 'endings' contain a much greater proportion of the total number of granules stored in the neural lobe than would be predicted if the readily releasable pool of hormone were composed of all the granules in the 'endings'. Some further constraint on granule release either physiological or anatomical (e.g. the position of the granule in relation to the plasmalemma of the 'ending') must be operative.", "contents": "Distribution of neurosecretory granules among the anatomical compartments of the neurosecretory processes of the pituitary gland: a quantitative ultrastructural approach to hormone storage in the neural lobe. The distribution of neurosecretory granules in various anatomical compartments of neurosecretory axons of the neural lobe of the rat pituitary has been studied. Apart from the most anterior tip of the gland, where granules are largely restricted to undilated axons and a few 'swellings', the proportional compartmental storage of granules is essentially homogeneous for the rest of the gland: 13% of granules are found in undilated axons, 31% in axonal 'endings' (which contain microvesicles and abut the basement membrane) and 55% in axonal 'swellings' (which are devoid of significant numbers of microvesicles). These values indicate that the 'endings' contain a much greater proportion of the total number of granules stored in the neural lobe than would be predicted if the readily releasable pool of hormone were composed of all the granules in the 'endings'. Some further constraint on granule release either physiological or anatomical (e.g. the position of the granule in relation to the plasmalemma of the 'ending') must be operative."} {"id": "PMID:1255040", "title": "Circadian rhythm of corticosterone levels in rat brain.", "content": "In the present study the circadian changes which occur in the levels of corticosterone in the brain and plasma in Sprague-Dawley rats are reported. The levels of corticosterone in the brain were found to have a daily trough and crest with timing similar to that observed for the plasma steroid. In addition, the effect of histamine stress on the corticosterone content of the particulate and the soluble fractions at the trough and crest was examined. The levels of both brain fractions were significantly higher 20 min after histamine injection. The time of day at which the stress was applied was not a significant factor in the magnitude of the stress response.", "contents": "Circadian rhythm of corticosterone levels in rat brain. In the present study the circadian changes which occur in the levels of corticosterone in the brain and plasma in Sprague-Dawley rats are reported. The levels of corticosterone in the brain were found to have a daily trough and crest with timing similar to that observed for the plasma steroid. In addition, the effect of histamine stress on the corticosterone content of the particulate and the soluble fractions at the trough and crest was examined. The levels of both brain fractions were significantly higher 20 min after histamine injection. The time of day at which the stress was applied was not a significant factor in the magnitude of the stress response."} {"id": "PMID:1255041", "title": "Effect of cortisol on utilization and hepatic release of glucose in the marsupial brush-tailed opossum, Trichosurus vulpecula.", "content": "Brush-tailed opossums were prepared surgically with indwelling heatic and jugular venous catheters for blood sampling without disturbance in the conscious state. Hepatic extraction of Rose Bengal was 21 +3 (s.d.) % and hepatic clearance, used as a measure of hepatic blood flow, was 42.5 +7 ml/kg/min. Hepatic relaease of new glucose, calculated from the thorias vena caval-hepatic venous difference in glucose specific activity at equilibrium during i.v. infusion of [14C]glucose and hepatic blood flow, was 3.5 + o.0 mg/kg/mim. This was not changed by i.v. infusions of 10% ethanolic aline or cortisol in ethanolic saline, at 1mg/kg/h for 90 min, although the cortisol infusion caused the peripheral blood glucose concentration to rise form 56.5 + 7.3 to 83.2 + 10.3 mg/100ml. The rate of metabolic clearance of glucose fell from 6.1 +1.1 to 4.2 +0.9 ml/kg/min during i.v. cortisol infusion. Daily i.m. injection of 1 mg cortisol accetate/kg for 5 days caused an increase in hepatic new glucose release to 8.0 + 1.6 mg/kg/min. The findings support the propostion that, in the marsupial, the short-term effect of cortisol on plasma glucose concentration is due to inhibition of peripheral glucose utilization, whereas the long-term effect is due to increased hepatic glucose production.", "contents": "Effect of cortisol on utilization and hepatic release of glucose in the marsupial brush-tailed opossum, Trichosurus vulpecula. Brush-tailed opossums were prepared surgically with indwelling heatic and jugular venous catheters for blood sampling without disturbance in the conscious state. Hepatic extraction of Rose Bengal was 21 +3 (s.d.) % and hepatic clearance, used as a measure of hepatic blood flow, was 42.5 +7 ml/kg/min. Hepatic relaease of new glucose, calculated from the thorias vena caval-hepatic venous difference in glucose specific activity at equilibrium during i.v. infusion of [14C]glucose and hepatic blood flow, was 3.5 + o.0 mg/kg/mim. This was not changed by i.v. infusions of 10% ethanolic aline or cortisol in ethanolic saline, at 1mg/kg/h for 90 min, although the cortisol infusion caused the peripheral blood glucose concentration to rise form 56.5 + 7.3 to 83.2 + 10.3 mg/100ml. The rate of metabolic clearance of glucose fell from 6.1 +1.1 to 4.2 +0.9 ml/kg/min during i.v. cortisol infusion. Daily i.m. injection of 1 mg cortisol accetate/kg for 5 days caused an increase in hepatic new glucose release to 8.0 + 1.6 mg/kg/min. The findings support the propostion that, in the marsupial, the short-term effect of cortisol on plasma glucose concentration is due to inhibition of peripheral glucose utilization, whereas the long-term effect is due to increased hepatic glucose production."} {"id": "PMID:1255042", "title": "Solvolysable deoxycorticosterone conjugates in human urine.", "content": "The nature of the urinary conjugate converted by solvolysis, to free unconjugated deoxycorticosterone (DOC) was studied. A comparison of 11 solvolysis techniques has shown that the method employed in this study yielded 86% of the highest yield by any of the techniques tried. Three successive chromatographic systems on paper showed that no appreciable amounts of contaminants were present in the free DOC eluates, following solvolysis. By preparing authentic [3H]DOC sulphate and subjecting it to solvolysis it was shown that more than 90% of the tritiated DOC was recovered, after chromatography of the free DOC extract. This suggests that much of the solvolysable DOC in human urine is present in the form of the sulphate conjugate. The levels of DOC, excreted as the solvolysable conjugate in a variety of urine specimens, were shown to be much higher than those of free DOC, the former being 4-8 to 127 times higher than the amount of the latter. This highly variable ratio suggests that the site of production of solvolysable DOC is different from that for free DOC. The only correlation between free and solvolysable DOC was shown in dexamethasone-suppressed patients, in whom the mean percentage remaining after suppression was 30-6% for free DOC, 24-1% for solvolysable DOC and 22-2% for cortisol. As solvolysable DOC is present in much larger amounts in urine, care is necessary in the storage of urine samples in which free DOC estimates are to be made, as we found that urine specimens left at room temperature for 1 week could show rises of as much as 400% of their starting free DOC levels.", "contents": "Solvolysable deoxycorticosterone conjugates in human urine. The nature of the urinary conjugate converted by solvolysis, to free unconjugated deoxycorticosterone (DOC) was studied. A comparison of 11 solvolysis techniques has shown that the method employed in this study yielded 86% of the highest yield by any of the techniques tried. Three successive chromatographic systems on paper showed that no appreciable amounts of contaminants were present in the free DOC eluates, following solvolysis. By preparing authentic [3H]DOC sulphate and subjecting it to solvolysis it was shown that more than 90% of the tritiated DOC was recovered, after chromatography of the free DOC extract. This suggests that much of the solvolysable DOC in human urine is present in the form of the sulphate conjugate. The levels of DOC, excreted as the solvolysable conjugate in a variety of urine specimens, were shown to be much higher than those of free DOC, the former being 4-8 to 127 times higher than the amount of the latter. This highly variable ratio suggests that the site of production of solvolysable DOC is different from that for free DOC. The only correlation between free and solvolysable DOC was shown in dexamethasone-suppressed patients, in whom the mean percentage remaining after suppression was 30-6% for free DOC, 24-1% for solvolysable DOC and 22-2% for cortisol. As solvolysable DOC is present in much larger amounts in urine, care is necessary in the storage of urine samples in which free DOC estimates are to be made, as we found that urine specimens left at room temperature for 1 week could show rises of as much as 400% of their starting free DOC levels."} {"id": "PMID:1255043", "title": "Metabolic clearance rate and production rate of oestradiol in conscious rabbits.", "content": "A continuous isotope infusion technique was used to measure the metabolic clearance rate (MCRB) and production rate (PRB) of oestradiol-17beta in a group of six non-pregnant conscious Chinchilla rabbits. The mean MCRB of oestradiol was 162 ml/min (0 X 079 1/min/weight0 X 75), and at equilibrium a significant proportion of the radioactivity in the circulation was present as oestrone (conversion ratio oestradiol to oestrone, 27 X 6%). The mean PRB of oestradiol was 4 X 3 ng/min, which is equivalent to about 5 mug/day. Some day-to-day variation was seen in the endogenous concentrations of oestradiol, oestrone and progesterone although in general the levels of the two oestrogens were less than 30-40 pg/ml, and progesterone levels were below 300 pg/ml apart from short peaks up to 600 pg/ml. These values were compared with previous measurements of the ovarian secretion rate of oestradiol measured directly in anaesthetized animals.", "contents": "Metabolic clearance rate and production rate of oestradiol in conscious rabbits. A continuous isotope infusion technique was used to measure the metabolic clearance rate (MCRB) and production rate (PRB) of oestradiol-17beta in a group of six non-pregnant conscious Chinchilla rabbits. The mean MCRB of oestradiol was 162 ml/min (0 X 079 1/min/weight0 X 75), and at equilibrium a significant proportion of the radioactivity in the circulation was present as oestrone (conversion ratio oestradiol to oestrone, 27 X 6%). The mean PRB of oestradiol was 4 X 3 ng/min, which is equivalent to about 5 mug/day. Some day-to-day variation was seen in the endogenous concentrations of oestradiol, oestrone and progesterone although in general the levels of the two oestrogens were less than 30-40 pg/ml, and progesterone levels were below 300 pg/ml apart from short peaks up to 600 pg/ml. These values were compared with previous measurements of the ovarian secretion rate of oestradiol measured directly in anaesthetized animals."} {"id": "PMID:1255044", "title": "Egg transport in ovariectomized rabbits as affected by different combinations of oestrogen and progesterone.", "content": "A total of 1548 eggs was transferred to the oviducts of rabbits ovariectomized 45 days to 7 months earlier. The pattern of egg transport was disrupted, and the majority of eggs were in the vagina 60-72 h after transfer. To determine the role of the ovarian hormones on egg transport, the effects of various combinations of oestrogen and progesterone were studied. None of the hormonal treatments produced the normal transport pattern and large proportions of transferred eggs were retained in the oviducts. It is concluded that as long as progesterone is the dominant hormone, eggs move very slowly through the isthmus, and that a surge of oestrogen is required to modify the action of progesterone and to speed the movement of eggs to the uterus.", "contents": "Egg transport in ovariectomized rabbits as affected by different combinations of oestrogen and progesterone. A total of 1548 eggs was transferred to the oviducts of rabbits ovariectomized 45 days to 7 months earlier. The pattern of egg transport was disrupted, and the majority of eggs were in the vagina 60-72 h after transfer. To determine the role of the ovarian hormones on egg transport, the effects of various combinations of oestrogen and progesterone were studied. None of the hormonal treatments produced the normal transport pattern and large proportions of transferred eggs were retained in the oviducts. It is concluded that as long as progesterone is the dominant hormone, eggs move very slowly through the isthmus, and that a surge of oestrogen is required to modify the action of progesterone and to speed the movement of eggs to the uterus."} {"id": "PMID:1255049", "title": "Stimulation of carp interrenal function by adrenocorticotrophin.", "content": "The effect of ACTH on cortisol concentration in the plasma of the carp has been studied; cortisol was determined using a competitive protein-binding radioassay. Blood was sampled at 12.00 h (the diurnal minimum) by cardiac puncture. The plasma cortisol level of undisturbed carp (blood obtained 1--3 min after netting) was 16 +/- 14 (S.E.M.) ng/ml. One hour after injection of ACTH (1-0 i.u./100 g body wt., i.m.) the level of cortisol increased to 415 +/- 62 ng/ml and reached a maximum of 656 +/- 62 ng/ml after 2 h. The level of cortisol in saline-injected control carp after 2 h was 72 +/- 33 ng/ml. A transient rise of cortisol was noted in both groups 30 min after injection (315 +/- 51, 315 +/- 62 ng/ml). This was attributed to a surge of endogenous ACTH, presumably due to handling. Carp head kidneys were superfused in vitro. They released cortisol spontaneously, but the releasing rate declined exponentially and reached a minimum after 135 min. Addition of ACTH to the medium was followed by a prompt increase in cortisol release. The rate of cortisol release was maximal 30--45 min after addition of ACTH and was identical to the rate at the beginning of the superfusion.", "contents": "Stimulation of carp interrenal function by adrenocorticotrophin. The effect of ACTH on cortisol concentration in the plasma of the carp has been studied; cortisol was determined using a competitive protein-binding radioassay. Blood was sampled at 12.00 h (the diurnal minimum) by cardiac puncture. The plasma cortisol level of undisturbed carp (blood obtained 1--3 min after netting) was 16 +/- 14 (S.E.M.) ng/ml. One hour after injection of ACTH (1-0 i.u./100 g body wt., i.m.) the level of cortisol increased to 415 +/- 62 ng/ml and reached a maximum of 656 +/- 62 ng/ml after 2 h. The level of cortisol in saline-injected control carp after 2 h was 72 +/- 33 ng/ml. A transient rise of cortisol was noted in both groups 30 min after injection (315 +/- 51, 315 +/- 62 ng/ml). This was attributed to a surge of endogenous ACTH, presumably due to handling. Carp head kidneys were superfused in vitro. They released cortisol spontaneously, but the releasing rate declined exponentially and reached a minimum after 135 min. Addition of ACTH to the medium was followed by a prompt increase in cortisol release. The rate of cortisol release was maximal 30--45 min after addition of ACTH and was identical to the rate at the beginning of the superfusion."} {"id": "PMID:1255050", "title": "Inability of actinomycin D to act upon the uterine refractory state resulting from nidatory oestrogen action in rats.", "content": "After priming with oestradiol, ovariectomized rats were given 6 days of progesterone treatment in which two doses of 50 ng oestradiol were superimposed on days 3 and 6. This basic regimen allows the oestradiol-induced (1st injection) inhibition of uterine sensitivity to decidual stimuli to appear. Actinomycin D given instead of, or together with, the first dose of oestradiol could not mimic, or prevent oestrogen action in the occurrence of the uterine refractory state. This drug was unable to interfere with the minimal 48 h progesterone treatment which is requisite to uterine sensitization. Our results together with other data from the literature, suggest that luteal hormones do not need to act at the transcriptional level to sensitize and desensitize the uterus to implantation.", "contents": "Inability of actinomycin D to act upon the uterine refractory state resulting from nidatory oestrogen action in rats. After priming with oestradiol, ovariectomized rats were given 6 days of progesterone treatment in which two doses of 50 ng oestradiol were superimposed on days 3 and 6. This basic regimen allows the oestradiol-induced (1st injection) inhibition of uterine sensitivity to decidual stimuli to appear. Actinomycin D given instead of, or together with, the first dose of oestradiol could not mimic, or prevent oestrogen action in the occurrence of the uterine refractory state. This drug was unable to interfere with the minimal 48 h progesterone treatment which is requisite to uterine sensitization. Our results together with other data from the literature, suggest that luteal hormones do not need to act at the transcriptional level to sensitize and desensitize the uterus to implantation."} {"id": "PMID:1255051", "title": "Placental lactogen in the cow.", "content": "Placental lactogen secretion has been demonstrated in cows on days 36, 178, 182 and 270 of pregnancy by co-culture of cotyledonary tissue with mouse mammary gland explants. Bovine placental lactogen probably originated from the foetal cotyledon and showed no detectable cross-reaction in immunoassays for bovine prolactin or growth hormone. Peripheral plasma samples collected from seven primiparous heifers at 2-week intervals throughout pregnancy showed a seasonal rhythm in prolactin concentration, measured by radioimmunoassay, with high levels in the summer. Monthly samples were bioassayed for total lactogenic activity by a rabbit mammary gland organ culture method. Postive responses were obtained only when prolactin levels were high (greater than 70 ng/ml), indicating that levels of placental lactogen in the circulation are much lower in the cow than in sheep, goats or women.", "contents": "Placental lactogen in the cow. Placental lactogen secretion has been demonstrated in cows on days 36, 178, 182 and 270 of pregnancy by co-culture of cotyledonary tissue with mouse mammary gland explants. Bovine placental lactogen probably originated from the foetal cotyledon and showed no detectable cross-reaction in immunoassays for bovine prolactin or growth hormone. Peripheral plasma samples collected from seven primiparous heifers at 2-week intervals throughout pregnancy showed a seasonal rhythm in prolactin concentration, measured by radioimmunoassay, with high levels in the summer. Monthly samples were bioassayed for total lactogenic activity by a rabbit mammary gland organ culture method. Postive responses were obtained only when prolactin levels were high (greater than 70 ng/ml), indicating that levels of placental lactogen in the circulation are much lower in the cow than in sheep, goats or women."} {"id": "PMID:1255052", "title": "The influence of oestradiol-17beta and progesterone on the contractility of the oviduct of the turtle, Chrysemys picta, in vitro.", "content": "The contractility of the oviduct of Chrysemys picta (the fresh-water turtle) was studied in vitro. Significant regional differences in contractile activity were observed. Contractions increased in amplitude and duration and decreased in frequency from the proximal to the distal end of the oviduct. Injections of oestradiol-17beta in vivo increased the amplitude of contractions and decreased the duration of the rest period in segments taken from the diatal end of the oviduct. In contrast, progesterone injections significantly reduced the duration of both contractile and resting periods.", "contents": "The influence of oestradiol-17beta and progesterone on the contractility of the oviduct of the turtle, Chrysemys picta, in vitro. The contractility of the oviduct of Chrysemys picta (the fresh-water turtle) was studied in vitro. Significant regional differences in contractile activity were observed. Contractions increased in amplitude and duration and decreased in frequency from the proximal to the distal end of the oviduct. Injections of oestradiol-17beta in vivo increased the amplitude of contractions and decreased the duration of the rest period in segments taken from the diatal end of the oviduct. In contrast, progesterone injections significantly reduced the duration of both contractile and resting periods."} {"id": "PMID:1255053", "title": "Uptake and metabolism in vivo of tritiated oestradiol-17beta in tissues of ageing female mice.", "content": "The uptake in vivo of tritiated oestradiol-17beta has been compared in young and aged ovariectomized CBA/H-T6 mice by examining the levels of radioactivity in tissues 1 h after injection. The specificity of oestradiol uptake was demonstrated by previous treatment of some animals with either diethylstilboestrol or progesterone. The levels of radioactivity in whole tissue extracts were similar in both age groups for the uterus, hypothalamus, cerebrum and serum, but the uptake in the pituitary gland was significantly lower in old mice. There was no evidence of altered hormone metabolism with age.", "contents": "Uptake and metabolism in vivo of tritiated oestradiol-17beta in tissues of ageing female mice. The uptake in vivo of tritiated oestradiol-17beta has been compared in young and aged ovariectomized CBA/H-T6 mice by examining the levels of radioactivity in tissues 1 h after injection. The specificity of oestradiol uptake was demonstrated by previous treatment of some animals with either diethylstilboestrol or progesterone. The levels of radioactivity in whole tissue extracts were similar in both age groups for the uterus, hypothalamus, cerebrum and serum, but the uptake in the pituitary gland was significantly lower in old mice. There was no evidence of altered hormone metabolism with age."} {"id": "PMID:1255061", "title": "Absorption of 125I-labelled sheep growth hormone in single proximal tubules of the rat kidney.", "content": "Techniques of kidney micropuncture and electron microscope autoradiography have been used to study the uptake of 125I-labelled sheep growth hormone (GH) in rat renal proximal tubules. After microperfusion of a proximal tubule with 125I-labelled GH, the transport of label by the tubular epithelium was studied autoradiographically at selected times up to 1 h. The sequential transfer of labelled material from tubule to microvilli, then to small and large apical vacuoles and finally to lysosomes followed the pattern of absorption that has been described for other proteins. Evidence of lysosomal degradation of the transported protein was obtained from studies in vitro; lysosomes isolated from the renal cortex rapidly converted 125I-labelled GH to products of lower molecular weight. In addition to the absorptive pathway through the intracellular vacuolar apparatus is appeared that there was also an alternative pathway, less well defined, whereby GH could be absorbed without being degraded.", "contents": "Absorption of 125I-labelled sheep growth hormone in single proximal tubules of the rat kidney. Techniques of kidney micropuncture and electron microscope autoradiography have been used to study the uptake of 125I-labelled sheep growth hormone (GH) in rat renal proximal tubules. After microperfusion of a proximal tubule with 125I-labelled GH, the transport of label by the tubular epithelium was studied autoradiographically at selected times up to 1 h. The sequential transfer of labelled material from tubule to microvilli, then to small and large apical vacuoles and finally to lysosomes followed the pattern of absorption that has been described for other proteins. Evidence of lysosomal degradation of the transported protein was obtained from studies in vitro; lysosomes isolated from the renal cortex rapidly converted 125I-labelled GH to products of lower molecular weight. In addition to the absorptive pathway through the intracellular vacuolar apparatus is appeared that there was also an alternative pathway, less well defined, whereby GH could be absorbed without being degraded."} {"id": "PMID:1255062", "title": "Corticosteroid binding by plasma proteins and the effects of oestrogens in the marsupial brush-tailed opossum, Trichosurus vulpecula (Kerr).", "content": "Using the techniques of equilibrium dialysis at 36 degrees C and gel filtration at 4 degrees C, a high-affinity, transcortin-like, corticosteroid binding system has been demonstrated in the blood plasma of the marsupial Trichosurus vulpecula. The affinity constant for non-albumin binding was 4-018 +/- 1-032 X 10(7) (S.C.) 1/mol for males and 4-046 +/- 0.981 X 10(7) for females. The concentration of non-albumin binding sites was 1-82 +/- 0.76 X 10(-7) mol/1 in males and 1-86 +/- 0-57 X 10(-7) mol/1 for females. Oestrogen administration, sufficient to cause marked hypertrophy of the genital tract in the femlaes, had no effect on the affinity constant or the concentration of the non-albumin binding sites in either males or females. The general condition of the animals deteriorated during oestrogen administration and there were significant falls in the concentrations of albumin and cortisol in the blood plasma. In one animal which died during oestrogen treatment, the adrenal glands were significantly hypertrophied.", "contents": "Corticosteroid binding by plasma proteins and the effects of oestrogens in the marsupial brush-tailed opossum, Trichosurus vulpecula (Kerr). Using the techniques of equilibrium dialysis at 36 degrees C and gel filtration at 4 degrees C, a high-affinity, transcortin-like, corticosteroid binding system has been demonstrated in the blood plasma of the marsupial Trichosurus vulpecula. The affinity constant for non-albumin binding was 4-018 +/- 1-032 X 10(7) (S.C.) 1/mol for males and 4-046 +/- 0.981 X 10(7) for females. The concentration of non-albumin binding sites was 1-82 +/- 0.76 X 10(-7) mol/1 in males and 1-86 +/- 0-57 X 10(-7) mol/1 for females. Oestrogen administration, sufficient to cause marked hypertrophy of the genital tract in the femlaes, had no effect on the affinity constant or the concentration of the non-albumin binding sites in either males or females. The general condition of the animals deteriorated during oestrogen administration and there were significant falls in the concentrations of albumin and cortisol in the blood plasma. In one animal which died during oestrogen treatment, the adrenal glands were significantly hypertrophied."} {"id": "PMID:1255063", "title": "A possible role for oxytocin in sperm transport in the male rabbit.", "content": "Administration of methallibure (50 mg/kg body weight, daily) to male rabbits resulted in a 45% reduction in sperm number in ejaculates obtained during the treatment period. Recovery occurred within 48 h after the last dose of methallibure. This decrease in sperm number did not occur when oxytocin (0-2 i.u./kg body weight) was administered simultaneously with methallibure. This suggests that methallibure prevents the release of oxytocin during ejaculation.", "contents": "A possible role for oxytocin in sperm transport in the male rabbit. Administration of methallibure (50 mg/kg body weight, daily) to male rabbits resulted in a 45% reduction in sperm number in ejaculates obtained during the treatment period. Recovery occurred within 48 h after the last dose of methallibure. This decrease in sperm number did not occur when oxytocin (0-2 i.u./kg body weight) was administered simultaneously with methallibure. This suggests that methallibure prevents the release of oxytocin during ejaculation."} {"id": "PMID:1255064", "title": "Behavioural responses to sex steroids of gonadectomized and sexually regressed quail.", "content": "The purpose of these experiments was to compare the behavioural and morphological effects of exogenous sex hormones in gonadectomized quail (Coturnix coturnix japonica) with those in quail having regressed gonads as a result of exposure to short days. In Expt 1, male quail were assigned to one of three treatment groups: (1) intact, exposed to 16 h light: 8 h darkness and injected with oil (group 16L); (2) gonadectomized, exposed to 16 h light: 8 h darkness and injected with 2-5 mg testosterone propionate (TP)/day (group 16L-castrated); and (3) intact, exposed to 8 h light: 16 h darkness, and injected with 2-5 mg TP/day (group 8L). Groups 16L-castrated and 8L responded similarly to testosterone, copulating with equal frequency and rapidity after the same number of days of treatment, and also developing proctodeal (foam) glands of a similar size. Only on day 7 of testosterone treatment did the results for these two groups differ. By day 14, the behaviour of both groups resembled that of the 16L birds. In Expt 2 female quail were assigned to the same three treatment groups, except that the hormone treatment was 25 mug oestradiol benzoate/day. Group 8L became sexually receptive sooner than the 16L-ovariectomized quail, but by day 13 both groups had oviducts of similar size, were equally receptive, and were as receptive as the 16L females. The results suggest that the effects of photoperiod on sexual behaviour in this species are mediated largley, if not wholly , by the gonads. They also suggest exposure to short days and surgical gonadectomy are rather similar experimental procedures in the quail.", "contents": "Behavioural responses to sex steroids of gonadectomized and sexually regressed quail. The purpose of these experiments was to compare the behavioural and morphological effects of exogenous sex hormones in gonadectomized quail (Coturnix coturnix japonica) with those in quail having regressed gonads as a result of exposure to short days. In Expt 1, male quail were assigned to one of three treatment groups: (1) intact, exposed to 16 h light: 8 h darkness and injected with oil (group 16L); (2) gonadectomized, exposed to 16 h light: 8 h darkness and injected with 2-5 mg testosterone propionate (TP)/day (group 16L-castrated); and (3) intact, exposed to 8 h light: 16 h darkness, and injected with 2-5 mg TP/day (group 8L). Groups 16L-castrated and 8L responded similarly to testosterone, copulating with equal frequency and rapidity after the same number of days of treatment, and also developing proctodeal (foam) glands of a similar size. Only on day 7 of testosterone treatment did the results for these two groups differ. By day 14, the behaviour of both groups resembled that of the 16L birds. In Expt 2 female quail were assigned to the same three treatment groups, except that the hormone treatment was 25 mug oestradiol benzoate/day. Group 8L became sexually receptive sooner than the 16L-ovariectomized quail, but by day 13 both groups had oviducts of similar size, were equally receptive, and were as receptive as the 16L females. The results suggest that the effects of photoperiod on sexual behaviour in this species are mediated largley, if not wholly , by the gonads. They also suggest exposure to short days and surgical gonadectomy are rather similar experimental procedures in the quail."} {"id": "PMID:1255065", "title": "Immunoreactive gastrin in differential and density gradient fractions of rat gastric mucosa.", "content": "Immunoreactive gastrin was measured in subcellular fractions of rat gastric mucosa. The sedimentational properties of subcellular gastrin-containing structures were distinct from those of mitochondria. After centrifugation in sucrose density gradients using a zonal rotor, the peak of immunoreactive gastrin was found in 1-17--1-18 g cm(-3) density sucrose (1-35 M; 39-5%, W/W). A thermolabile component with 125I-labelled gastrin-binding activity present in gastric mucosal homogenates and fractions was not associated with the gastrin storage vesicles sedimenting in density gradients.", "contents": "Immunoreactive gastrin in differential and density gradient fractions of rat gastric mucosa. Immunoreactive gastrin was measured in subcellular fractions of rat gastric mucosa. The sedimentational properties of subcellular gastrin-containing structures were distinct from those of mitochondria. After centrifugation in sucrose density gradients using a zonal rotor, the peak of immunoreactive gastrin was found in 1-17--1-18 g cm(-3) density sucrose (1-35 M; 39-5%, W/W). A thermolabile component with 125I-labelled gastrin-binding activity present in gastric mucosal homogenates and fractions was not associated with the gastrin storage vesicles sedimenting in density gradients."} {"id": "PMID:1255066", "title": "Incorporation of radioactive precursors into the membrane and contents of the neurosecretory granules of the rat neurohypophysis as a method of studying their fate.", "content": "Rat neural lobes have been separated into subcellular fractions by differential centrifugation at various times after an intracisternal injection of [35S]cysteine or [3H]choline. Both isotopes led to a rise and fall in the radioactivity of neurosecretory granules (NSG) which paralleled that found previously for the neurohypophysial hormones and the neurophysins. While the radioactivity of the NSGs resulting from [35S]cysteine injection was predominantly associated with granular contents, [3H]choline injections led to a preferential labelling of the granular membrane. There was no indication of a sequential movement of radioactivity from the NSG-membrane fraction into the microsomal fraction (containing the so-called small vesicles) which might be expected if granular membrane were recaptured as small vesicles after release of secretory product by exocytosis. When release was stimulated in injected animals by giving them 2% NaCl solution to drink, 35S diappeared from the gland as expected, but 3H was retained and, moreover, appeared in the NSG-membrane fraction; results compatible with membrane conservation occurring by recapture of large vesicles. There was an indication that some of the neurophysin in the NSG was membrane-bound and that this too was retained after release of the granular contents.", "contents": "Incorporation of radioactive precursors into the membrane and contents of the neurosecretory granules of the rat neurohypophysis as a method of studying their fate. Rat neural lobes have been separated into subcellular fractions by differential centrifugation at various times after an intracisternal injection of [35S]cysteine or [3H]choline. Both isotopes led to a rise and fall in the radioactivity of neurosecretory granules (NSG) which paralleled that found previously for the neurohypophysial hormones and the neurophysins. While the radioactivity of the NSGs resulting from [35S]cysteine injection was predominantly associated with granular contents, [3H]choline injections led to a preferential labelling of the granular membrane. There was no indication of a sequential movement of radioactivity from the NSG-membrane fraction into the microsomal fraction (containing the so-called small vesicles) which might be expected if granular membrane were recaptured as small vesicles after release of secretory product by exocytosis. When release was stimulated in injected animals by giving them 2% NaCl solution to drink, 35S diappeared from the gland as expected, but 3H was retained and, moreover, appeared in the NSG-membrane fraction; results compatible with membrane conservation occurring by recapture of large vesicles. There was an indication that some of the neurophysin in the NSG was membrane-bound and that this too was retained after release of the granular contents."} {"id": "PMID:1255091", "title": "Prolactin inhibition test with L-dopa: decrease and restoration of plasma prolactin levels in the rat by a peripheral process.", "content": "L-DOPA, within 30 min after administration, induced a highly significant decrease of plasma prolactin levels (phase 1) in a number of groups of rats, differing in age and/or endocrine status, apparently by direct inhibition of prolactin release from the pituitary. Three hours after administration of L-DOPA these low plasma prolactin concentrations in treated animals had increased (phase 2) and did not differ significantly from levels in control animals, indicating that the effect of L-DOPA on plasma prolactin levels is only of short duration. During this process some interesting phenomena were observed, especially in the animals treated with oestrone. The elimination rate of prolactin from plasma was very high (t 1/2 = 2.8 min), as indicated by decreasing concentrations of the hormone during phase 1. Pituitary prolactin content did not change during phase 1, suggesting that prolactin synthesis was also stopped. Notwithstanding the high elimination rate, plasma prolactin regained initial concentrations in phase 2, suggesting release of a substantial part of the pituitary prolactin content. The latter,however, remained constant during the whole experiment (i.e. before L-DOPA administration and during phase 1 as well as phase 2). The results suggested another working mechanism of L-DOPA in decreasing plasma prolactin levels, namely by stimulating the uptake of this hormone in the periphery. After the effect of L-DOPA had ceased, most of the prolactin from the periphery returned into the bloodstream, causing a rapid restoration of plasma prolactin levels without substantial release from the pituitary. The nature of the processes responsible for the peripheral uptake of prolactin is discussed.", "contents": "Prolactin inhibition test with L-dopa: decrease and restoration of plasma prolactin levels in the rat by a peripheral process. L-DOPA, within 30 min after administration, induced a highly significant decrease of plasma prolactin levels (phase 1) in a number of groups of rats, differing in age and/or endocrine status, apparently by direct inhibition of prolactin release from the pituitary. Three hours after administration of L-DOPA these low plasma prolactin concentrations in treated animals had increased (phase 2) and did not differ significantly from levels in control animals, indicating that the effect of L-DOPA on plasma prolactin levels is only of short duration. During this process some interesting phenomena were observed, especially in the animals treated with oestrone. The elimination rate of prolactin from plasma was very high (t 1/2 = 2.8 min), as indicated by decreasing concentrations of the hormone during phase 1. Pituitary prolactin content did not change during phase 1, suggesting that prolactin synthesis was also stopped. Notwithstanding the high elimination rate, plasma prolactin regained initial concentrations in phase 2, suggesting release of a substantial part of the pituitary prolactin content. The latter,however, remained constant during the whole experiment (i.e. before L-DOPA administration and during phase 1 as well as phase 2). The results suggested another working mechanism of L-DOPA in decreasing plasma prolactin levels, namely by stimulating the uptake of this hormone in the periphery. After the effect of L-DOPA had ceased, most of the prolactin from the periphery returned into the bloodstream, causing a rapid restoration of plasma prolactin levels without substantial release from the pituitary. The nature of the processes responsible for the peripheral uptake of prolactin is discussed."} {"id": "PMID:1255094", "title": "Parturition in the goat: plasma concentrations of prostaglandin F and steroid hormones and uterine activity during late pregnancy and parturition.", "content": "Changes in plasma concentrations of hormones and uterine activity associated with spontaneous parturition in the goat were examined. No change in oestradiol-17beta concentration was detected during the experimental period, but oestradiol-17alpha consistently increased in concentration 3-4 days before parturition. This was followed by an increase in prostaglandin F two days later, while a pre-partum decline in progesterone concentration occurred 18-20 h after the significant increase in prostaglandin F. The onset of uterine contractions coincided with a significant decline in progesterone concentration and a period of continually rising prostaglandin F and oestradiol-17alpha concentrations. Uterine activity expressed in Montevideo units did not change until 10-8 h before foetal expulsion. These results support the hypothesis that in the goat the elevated prepartum concentration of prostaglandin F brings about luteolysis and a subsequent decline in progesterone concentration.", "contents": "Parturition in the goat: plasma concentrations of prostaglandin F and steroid hormones and uterine activity during late pregnancy and parturition. Changes in plasma concentrations of hormones and uterine activity associated with spontaneous parturition in the goat were examined. No change in oestradiol-17beta concentration was detected during the experimental period, but oestradiol-17alpha consistently increased in concentration 3-4 days before parturition. This was followed by an increase in prostaglandin F two days later, while a pre-partum decline in progesterone concentration occurred 18-20 h after the significant increase in prostaglandin F. The onset of uterine contractions coincided with a significant decline in progesterone concentration and a period of continually rising prostaglandin F and oestradiol-17alpha concentrations. Uterine activity expressed in Montevideo units did not change until 10-8 h before foetal expulsion. These results support the hypothesis that in the goat the elevated prepartum concentration of prostaglandin F brings about luteolysis and a subsequent decline in progesterone concentration."} {"id": "PMID:1255096", "title": "Oestrogens and prolactin as possible regulators of puberty.", "content": "At day 15 after birth, high serum oestradiol levels, high FSH levels and occasionally high LH levels were observed in control female rats. Injections of potent and specific antisera for oestrogen between days 8-15 prevented LH peaks and decreased basal LH levels. Serum FSH levels were increased after treatment. High oestradiol levels at this time appear to exert a positive feedback action on phasic as well as tonic LH release. Injections of ovine prolactin (0.5 mug/g body wt twice daily) between days 8-25 of life significantly advanced the day of vaginal opening in immature rats and initiated regular oestrous cycles. Such treatment completely prevented high LH levels at day 15 but serum FSH levels remained high. Prolactin and progesterone levels were higher at day 25 than at day 15 in control rats and at that time LH and FSH levels were low. Prolactin treatment had a depressant effect on endogenous prolactin and progesterone levels. It is proposed that after day 20 the positive feedback threshold of oestradiol on LH release is at a mature, highly sensitive level. The steady increment in serum prolactin and/or progesterone levels between day 20 and puberty, however, inhibited phasic LH release thus preventing early puberty. The possible mechanisms of action of prolactin are discussed.", "contents": "Oestrogens and prolactin as possible regulators of puberty. At day 15 after birth, high serum oestradiol levels, high FSH levels and occasionally high LH levels were observed in control female rats. Injections of potent and specific antisera for oestrogen between days 8-15 prevented LH peaks and decreased basal LH levels. Serum FSH levels were increased after treatment. High oestradiol levels at this time appear to exert a positive feedback action on phasic as well as tonic LH release. Injections of ovine prolactin (0.5 mug/g body wt twice daily) between days 8-25 of life significantly advanced the day of vaginal opening in immature rats and initiated regular oestrous cycles. Such treatment completely prevented high LH levels at day 15 but serum FSH levels remained high. Prolactin and progesterone levels were higher at day 25 than at day 15 in control rats and at that time LH and FSH levels were low. Prolactin treatment had a depressant effect on endogenous prolactin and progesterone levels. It is proposed that after day 20 the positive feedback threshold of oestradiol on LH release is at a mature, highly sensitive level. The steady increment in serum prolactin and/or progesterone levels between day 20 and puberty, however, inhibited phasic LH release thus preventing early puberty. The possible mechanisms of action of prolactin are discussed."} {"id": "PMID:1255097", "title": "Inhibition of human chorionic gonadotrophin-induced hypertrophy of the ovaries and uterus in immature mice by some pineal indoles, 6-hydroxymelatonin and arginine vasotocin.", "content": "Administration of the indoles 5-methoxytryptophol, 6-hydroxymelatonin, melatonin, N-acetylserotonin or 5-methoxyindole-3-acetic acid (six 100-mug injections given at intervals of 12 h) inhibited both the absolute and relative ovarian and uterine weights of immature female mice pre-treated with HCG. Administration of 5-hydroxytryptophol or 5-methoxytryptamine at the same dosage inhibited ovarian but not uterine hypertrophy in mice pre-treated with HCG.", "contents": "Inhibition of human chorionic gonadotrophin-induced hypertrophy of the ovaries and uterus in immature mice by some pineal indoles, 6-hydroxymelatonin and arginine vasotocin. Administration of the indoles 5-methoxytryptophol, 6-hydroxymelatonin, melatonin, N-acetylserotonin or 5-methoxyindole-3-acetic acid (six 100-mug injections given at intervals of 12 h) inhibited both the absolute and relative ovarian and uterine weights of immature female mice pre-treated with HCG. Administration of 5-hydroxytryptophol or 5-methoxytryptamine at the same dosage inhibited ovarian but not uterine hypertrophy in mice pre-treated with HCG."} {"id": "PMID:1255104", "title": "Role of maternal and foetal adrenal activity in the development of the rat mammary gland near term.", "content": "The essential role of adrenal corticosteroids in the initiation of mammary gland secretory activity near term in the rat has been investigated. Mammary gland DNA and RNA were estimated as a quantitative indication of the extent of mammary gland development. Maternal adrenalectomy or hypophysectomy resulted in a decrease in the mammary gland RNA:DNA ratio. Treatment of adrenalectomized animals with cortisol acetate completely restored the RNA:DNA ratio to the control level. Treatment of hypophysectomized animals with cortisol acetate resulted in an increase in the RNA:DNA ratio but did not restore the ratio to the control level. Removal of the pups had no effect on the RNA:DNA ratio. The findings are discussed in relation to the foetal and maternal contribution to the level of glucocorticoids in the circulation and with respect to changes in mammary gland sensitivity to lactogenic stimulation near term.", "contents": "Role of maternal and foetal adrenal activity in the development of the rat mammary gland near term. The essential role of adrenal corticosteroids in the initiation of mammary gland secretory activity near term in the rat has been investigated. Mammary gland DNA and RNA were estimated as a quantitative indication of the extent of mammary gland development. Maternal adrenalectomy or hypophysectomy resulted in a decrease in the mammary gland RNA:DNA ratio. Treatment of adrenalectomized animals with cortisol acetate completely restored the RNA:DNA ratio to the control level. Treatment of hypophysectomized animals with cortisol acetate resulted in an increase in the RNA:DNA ratio but did not restore the ratio to the control level. Removal of the pups had no effect on the RNA:DNA ratio. The findings are discussed in relation to the foetal and maternal contribution to the level of glucocorticoids in the circulation and with respect to changes in mammary gland sensitivity to lactogenic stimulation near term."} {"id": "PMID:1255105", "title": "Tamoxifen as an anti-tumour agent: oestrogen binding as a predictive test for tumour response.", "content": "Rats with growing 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced rat mammary carcinomata were biopsied and oestrogen-binding capacity was measured using a Sephadex LH-20 chromatography method. Tumours were measured with calipers and animals were treated for 3 weeks with tamoxifen (50 mug/day, S.C.). Tumour response was determined by the size (cm2) before and after therapy. An increase in tumour regression (ten tumours) was seen with increasing oestrogen-binding sites determined by Scatchard analysis (P less than 0.01). Thirty tumours were used to determine oestrogen binding with a single dose of [3H]-oestradiol. The percentage tumour regression was linearly correlated with oestrogen-binding capacity (P less than 0.01), although some tumours with high oestrogen-binding capacities only partially regressed in response to tamoxifen therapy. The time of the oestrous cycle when biopsy occurred was not a critical factor in determining oestrogen binding for prediction of response. Oestrogen binding was reduced during tamoxifen therapy.", "contents": "Tamoxifen as an anti-tumour agent: oestrogen binding as a predictive test for tumour response. Rats with growing 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced rat mammary carcinomata were biopsied and oestrogen-binding capacity was measured using a Sephadex LH-20 chromatography method. Tumours were measured with calipers and animals were treated for 3 weeks with tamoxifen (50 mug/day, S.C.). Tumour response was determined by the size (cm2) before and after therapy. An increase in tumour regression (ten tumours) was seen with increasing oestrogen-binding sites determined by Scatchard analysis (P less than 0.01). Thirty tumours were used to determine oestrogen binding with a single dose of [3H]-oestradiol. The percentage tumour regression was linearly correlated with oestrogen-binding capacity (P less than 0.01), although some tumours with high oestrogen-binding capacities only partially regressed in response to tamoxifen therapy. The time of the oestrous cycle when biopsy occurred was not a critical factor in determining oestrogen binding for prediction of response. Oestrogen binding was reduced during tamoxifen therapy."} {"id": "PMID:1255106", "title": "Effect of luteinizing hormone releasing hormone on plasma levels of luteinizing hormone, oestradiol and testosterone in the male dog.", "content": "An injection of luteinizing hormone releasing hormone (LH-RH) increased plasma LH and testosterone concentrations in the male dog, but no significant increase in plasma oestradiol-17beta levels was observed. Repeated injections of LH-RH produced an increase in plasma LH levels but there was a progressive decline in the response with each injection. The concentration of plasma testosterone reached a maximum within 40 min of the first injection of LH-RH and remained constant thereafter while plasma oestradiol concentration gradually increased with successive injections of LH-RH.", "contents": "Effect of luteinizing hormone releasing hormone on plasma levels of luteinizing hormone, oestradiol and testosterone in the male dog. An injection of luteinizing hormone releasing hormone (LH-RH) increased plasma LH and testosterone concentrations in the male dog, but no significant increase in plasma oestradiol-17beta levels was observed. Repeated injections of LH-RH produced an increase in plasma LH levels but there was a progressive decline in the response with each injection. The concentration of plasma testosterone reached a maximum within 40 min of the first injection of LH-RH and remained constant thereafter while plasma oestradiol concentration gradually increased with successive injections of LH-RH."} {"id": "PMID:1255114", "title": "The effects of antigen on the migration of recirculating lymphocytes through single lymph nodes.", "content": "The increased input of RL into LN starts within 3 h after antigenic stimulation and is due to an increase in the number of RL passing through a LN. It is not associated with an altered transit time through a LN of the majority of RL and it cannot occur in the absence of high endothelial PCV. The immediate decrease in the output of RL from an antigen-stimulated LN is due to a delay in the exit from that LN of RL which had entered the LN before antigen was given. The decrease in cell output from a LN after antigen administration affects blast cells produced within the LN as well as small lymphocytes and is not specific for RL. There are at least two distinct mechanisms controlling the migration of RL through an antigen-stimulated LN. The first controls the increased input of RL which occurs only through high endothelial PCV. The second controls the immediate decrease in cell output, which although it does not occur at the level of the high endothelial PCV, can only occur in organized lymphoid tissue. The increased input of RL into an antigen-stimulated LN and the decreased cell output from the LN can occur independently and are possibly controlled by different mechanisms.", "contents": "The effects of antigen on the migration of recirculating lymphocytes through single lymph nodes. The increased input of RL into LN starts within 3 h after antigenic stimulation and is due to an increase in the number of RL passing through a LN. It is not associated with an altered transit time through a LN of the majority of RL and it cannot occur in the absence of high endothelial PCV. The immediate decrease in the output of RL from an antigen-stimulated LN is due to a delay in the exit from that LN of RL which had entered the LN before antigen was given. The decrease in cell output from a LN after antigen administration affects blast cells produced within the LN as well as small lymphocytes and is not specific for RL. There are at least two distinct mechanisms controlling the migration of RL through an antigen-stimulated LN. The first controls the increased input of RL which occurs only through high endothelial PCV. The second controls the immediate decrease in cell output, which although it does not occur at the level of the high endothelial PCV, can only occur in organized lymphoid tissue. The increased input of RL into an antigen-stimulated LN and the decreased cell output from the LN can occur independently and are possibly controlled by different mechanisms."} {"id": "PMID:1255115", "title": "Inclusion group systems and cis-trans effects in responses controlled by the two complementing Ir-GLphi genes.", "content": "The immune responses to the random linear terpolymers of L-amino acids, poly-(glu57, lys38, tyr5), poly-(glu51, lys34, tyr15,), and poly-(glu53, lys36, phe11) are each controlled by two dominant H-linked Ir genes. The immune responses to these three related terpolymers demonstrate different H-2 distributions, however, the H-2 patterns are part of a single inclusion group system. The alpha- and beta-genes are dominant; however, most effective gene interactions occur when the two genes are in the cis configuration. The potential significance of this cis-trans effect is discussed.", "contents": "Inclusion group systems and cis-trans effects in responses controlled by the two complementing Ir-GLphi genes. The immune responses to the random linear terpolymers of L-amino acids, poly-(glu57, lys38, tyr5), poly-(glu51, lys34, tyr15,), and poly-(glu53, lys36, phe11) are each controlled by two dominant H-linked Ir genes. The immune responses to these three related terpolymers demonstrate different H-2 distributions, however, the H-2 patterns are part of a single inclusion group system. The alpha- and beta-genes are dominant; however, most effective gene interactions occur when the two genes are in the cis configuration. The potential significance of this cis-trans effect is discussed."} {"id": "PMID:1255116", "title": "Differences between pig tissues in the expression of major transplantation antigens: possible relevance for organ allografts.", "content": "Evidence is presented that there are differences between pig liver and kidney parenchymal cells in the expression of major histocompatibility complex antigens. Analogues of I-region antigens of the mouse are detectable on kidney cells and some peripheral blood leukocytes (PBL) but not on liver, platelets, and other PBL. Such differences between liver and kidney may explain (a) the fate of these organs as allografts and (b) the donor-specific protection of kidney by liver. Other antigens peculiar to skin and kidney have been detected but require further characterization.", "contents": "Differences between pig tissues in the expression of major transplantation antigens: possible relevance for organ allografts. Evidence is presented that there are differences between pig liver and kidney parenchymal cells in the expression of major histocompatibility complex antigens. Analogues of I-region antigens of the mouse are detectable on kidney cells and some peripheral blood leukocytes (PBL) but not on liver, platelets, and other PBL. Such differences between liver and kidney may explain (a) the fate of these organs as allografts and (b) the donor-specific protection of kidney by liver. Other antigens peculiar to skin and kidney have been detected but require further characterization."} {"id": "PMID:1255117", "title": "Effects on adult newt limb regeneration of partial and complete skin flaps over the amputation surface.", "content": "The influence of the wound epithelium on the cellular events preceding blastema formation was examined by comparing dedifferentiation, DNA labeling indices, and mitotic indices of the distal mesodermal tissues in control regenerating newt forelimbs and in amputated forelimbs covered with a flap of full thickness skin. Three kinds of results were seen following the skin-flap graft operations. Epidermal migration across the amputation surface was completely inhibited in 22% (8) of the cases and these limbs repaired the amputation wound but did not form regeneration blastemas. In 11% (4) of the experimental limbs, essentially normal wound epithelia displaced the skin flaps and the limb stumps formed blastemas and regenerated. The majority of the skin grafts (67%) exhibited epidermal migration restricted to the free edges of the flaps. These limbs formed eccentric blastemas on the ventral side of the limb next to the dermis-free epidermis and regenerated laterally in that direction.", "contents": "Effects on adult newt limb regeneration of partial and complete skin flaps over the amputation surface. The influence of the wound epithelium on the cellular events preceding blastema formation was examined by comparing dedifferentiation, DNA labeling indices, and mitotic indices of the distal mesodermal tissues in control regenerating newt forelimbs and in amputated forelimbs covered with a flap of full thickness skin. Three kinds of results were seen following the skin-flap graft operations. Epidermal migration across the amputation surface was completely inhibited in 22% (8) of the cases and these limbs repaired the amputation wound but did not form regeneration blastemas. In 11% (4) of the experimental limbs, essentially normal wound epithelia displaced the skin flaps and the limb stumps formed blastemas and regenerated. The majority of the skin grafts (67%) exhibited epidermal migration restricted to the free edges of the flaps. These limbs formed eccentric blastemas on the ventral side of the limb next to the dermis-free epidermis and regenerated laterally in that direction."} {"id": "PMID:1255118", "title": "Evidence for the role of a trypsin-like enzyme in the hamster sperm acrosome reaction.", "content": "Acrosome reactions occurring in vitro in hamster sperm capacitated by bovine follicular fluid were severly inhibited by four synthetic trypsin inhibitors and by Zn2+. Three polypeptide trypsin inhibitors and a synthetic chymotrypsin inhibitor did not inhibit the acrosome reaction, and Ca2+ overcame the inhibition by Zn2+. These results suggest that a trypsin-like enzyme (possibly acrosin) plays a role in the acrosome reaction.", "contents": "Evidence for the role of a trypsin-like enzyme in the hamster sperm acrosome reaction. Acrosome reactions occurring in vitro in hamster sperm capacitated by bovine follicular fluid were severly inhibited by four synthetic trypsin inhibitors and by Zn2+. Three polypeptide trypsin inhibitors and a synthetic chymotrypsin inhibitor did not inhibit the acrosome reaction, and Ca2+ overcame the inhibition by Zn2+. These results suggest that a trypsin-like enzyme (possibly acrosin) plays a role in the acrosome reaction."} {"id": "PMID:1255119", "title": "Spontaneous maturation of oocytes isolated from ovaries of immature hypophysectomized rats.", "content": "Oocytes were collected from preantral follicles (200-300 mu in diameter) from 30-day-old immature rats 7 days after hypophysectomy. The ova were cultured in vitro for 17 hrs in a chemically defined medium and scored cytologically for meiotic maturation. Of 534 oocytes that were cultured 89% resumed meiosis; however, 98% of these oocytes arrested in either metaphase or anaphase I. In contrast, 82% of the oocytes isolated from preovulatory follicles (approximately 600 mu in diameter) of adult proestrus rats progressed to metaphase II. These results are discussed in terms of functional FSH and LH receptors on the granulosa cells.", "contents": "Spontaneous maturation of oocytes isolated from ovaries of immature hypophysectomized rats. Oocytes were collected from preantral follicles (200-300 mu in diameter) from 30-day-old immature rats 7 days after hypophysectomy. The ova were cultured in vitro for 17 hrs in a chemically defined medium and scored cytologically for meiotic maturation. Of 534 oocytes that were cultured 89% resumed meiosis; however, 98% of these oocytes arrested in either metaphase or anaphase I. In contrast, 82% of the oocytes isolated from preovulatory follicles (approximately 600 mu in diameter) of adult proestrus rats progressed to metaphase II. These results are discussed in terms of functional FSH and LH receptors on the granulosa cells."} {"id": "PMID:1255120", "title": "Neurohemal organ extracts effect the ventilation oscillator in crustaceans.", "content": "Extracts of the pericardial organs of crabs injected into intact animals cause an increase in the frequency of scaphognathite beating. The active factor is not dopamine of 5-hydroxytryptamine, which are present in pericardial organs; it is probably a peptide. The factor may represent a hormonal mechanism of coordinating heart rate and ventilation.", "contents": "Neurohemal organ extracts effect the ventilation oscillator in crustaceans. Extracts of the pericardial organs of crabs injected into intact animals cause an increase in the frequency of scaphognathite beating. The active factor is not dopamine of 5-hydroxytryptamine, which are present in pericardial organs; it is probably a peptide. The factor may represent a hormonal mechanism of coordinating heart rate and ventilation."} {"id": "PMID:1255121", "title": "Changes in volume of the rhabdom in the compound eye of Aedes aegypti L.", "content": "The volume of the rhabdom in compound eyes of mosquitoes decreases upon illumination. This decrease is probably mediated by a bleaching of the visual pigment, since blue light is most effective in producing the change and red light is least effective. The reduction in rhabdom volume appears to be a result of rhabdomal membrane loss to coated vesicles and multivesicular bodies. These organelles were seen most frequently in blue adapted eyes, markedly less frequently in red adapted eyes, and only rarely in dark adapted eyes.", "contents": "Changes in volume of the rhabdom in the compound eye of Aedes aegypti L. The volume of the rhabdom in compound eyes of mosquitoes decreases upon illumination. This decrease is probably mediated by a bleaching of the visual pigment, since blue light is most effective in producing the change and red light is least effective. The reduction in rhabdom volume appears to be a result of rhabdomal membrane loss to coated vesicles and multivesicular bodies. These organelles were seen most frequently in blue adapted eyes, markedly less frequently in red adapted eyes, and only rarely in dark adapted eyes."} {"id": "PMID:1255122", "title": "Biosynthesis of lipovitellin by the crustacean ovary. II. Characterization of and in vitro incorporation of amino acids into the purified subunits.", "content": "The amino acid composition has been determined for two of the five subunits of the crayfish lipovitellin. In addition the molecular weight of each subunit has also been ascertained. Most importantly, it is demonstrated that following in vitro incubation radioactive amino acids are incorporated into each of three purified subunits. These data strongly support the suggestion that the vitellogenic ovary of the crayfish is capable of in situ synthesis of lipovitellin.", "contents": "Biosynthesis of lipovitellin by the crustacean ovary. II. Characterization of and in vitro incorporation of amino acids into the purified subunits. The amino acid composition has been determined for two of the five subunits of the crayfish lipovitellin. In addition the molecular weight of each subunit has also been ascertained. Most importantly, it is demonstrated that following in vitro incubation radioactive amino acids are incorporated into each of three purified subunits. These data strongly support the suggestion that the vitellogenic ovary of the crayfish is capable of in situ synthesis of lipovitellin."} {"id": "PMID:1255123", "title": "Cleavage initiation activities of microtubules and in vitro reassembled tubulins of sperm flagella.", "content": "Cleavage of fish (Oryzias latipes) eggs was induced by injection of heterologous (sea urchin Hemicentrotus pulcherrimus and oyster Crassostrea gigas) sperm microtubules. Cleavage initiating CI activity of microtubules was higher in 3% PVP suspension than in 6% BSA, and not affected significantly by the concentration of microtubules themselves. The CI activity of microtubules suspended in 3% PVP was comparatively stable in the frozen state. Heat-treatment at more than 55 degrees C resulted in the loss of most or all of their CI activity. Such activity was observed in side-by-side aggregates of tubulin linear polymers of sea urchin (Hemicentrotus pulcherrimus) spermatozoa but not in dispersed linear polymers or tubulin dimers. Microtubules with CI activity seem to participate in initiating cleavage as astral centers, or a \"seed\" for polymerization of ooplasmic tubulins in activated eggs.", "contents": "Cleavage initiation activities of microtubules and in vitro reassembled tubulins of sperm flagella. Cleavage of fish (Oryzias latipes) eggs was induced by injection of heterologous (sea urchin Hemicentrotus pulcherrimus and oyster Crassostrea gigas) sperm microtubules. Cleavage initiating CI activity of microtubules was higher in 3% PVP suspension than in 6% BSA, and not affected significantly by the concentration of microtubules themselves. The CI activity of microtubules suspended in 3% PVP was comparatively stable in the frozen state. Heat-treatment at more than 55 degrees C resulted in the loss of most or all of their CI activity. Such activity was observed in side-by-side aggregates of tubulin linear polymers of sea urchin (Hemicentrotus pulcherrimus) spermatozoa but not in dispersed linear polymers or tubulin dimers. Microtubules with CI activity seem to participate in initiating cleavage as astral centers, or a \"seed\" for polymerization of ooplasmic tubulins in activated eggs."} {"id": "PMID:1255124", "title": "Time-course of potential spread along a skeletal muscle fiber under voltage clamp.", "content": "The equations describing the time-course of potential spread into a terminated segment of muscle fiber are given for the condition that a step of voltage is applied at x - 2l. Measurements of V(2l) - V(l) were made at 16.7-19.5 degrees C, using a three-microelectrode voltage clamp, to compare with the theory. Best least squares fits of calculated curves to data obtained in Ringer's solution (5 mM K) gave GL = 10 mumho/cm and Cm' = 1.6 muF/cm2. Similar measurements in 100 mM K solution, with the inward rectifier shut off by a positive prepulse, gave GL = 20 mumho/cm and Cm' = 2.0 muF/cm2. The time-course of V(2l) - V(l), measured when the inward rectifier was fully activated by a negative prepulse, was in good agreement with the curve calculated assuming no change in GL and Cm' and that the only effect of the negative prepulse was to increase the conductance of surface and tubular membranes.", "contents": "Time-course of potential spread along a skeletal muscle fiber under voltage clamp. The equations describing the time-course of potential spread into a terminated segment of muscle fiber are given for the condition that a step of voltage is applied at x - 2l. Measurements of V(2l) - V(l) were made at 16.7-19.5 degrees C, using a three-microelectrode voltage clamp, to compare with the theory. Best least squares fits of calculated curves to data obtained in Ringer's solution (5 mM K) gave GL = 10 mumho/cm and Cm' = 1.6 muF/cm2. Similar measurements in 100 mM K solution, with the inward rectifier shut off by a positive prepulse, gave GL = 20 mumho/cm and Cm' = 2.0 muF/cm2. The time-course of V(2l) - V(l), measured when the inward rectifier was fully activated by a negative prepulse, was in good agreement with the curve calculated assuming no change in GL and Cm' and that the only effect of the negative prepulse was to increase the conductance of surface and tubular membranes."} {"id": "PMID:1255125", "title": "Sensitivity of the sodium and potassium channels of Myxicola giant axons to changes in external pH.", "content": "Myxicola giant axons were studied using standard voltage-clamp techniques in solutions whose pH values ranged from 3.9 to 10.2. Buffer concentrations of 50 mM or greater were necessary to demonstrate the full effect of pH. In acidic solutions the axon underwent a variable depolarization, and both the sodium and potassium conductances were reversibly depressed with approximate pKa's of 4.8 and 4.4, respectively. The voltage dependence of GNa was only slightly altered by acidic conditions, whereas there occurred large shifts in GK along the voltage axis consistent with a substantial decrease in net negative surface charge in the vicinity of the K+ channels. The sodium and potassium activation rate constants were decreased by acidic conditions, but the results could not be described as a simple translation along the voltage axis.", "contents": "Sensitivity of the sodium and potassium channels of Myxicola giant axons to changes in external pH. Myxicola giant axons were studied using standard voltage-clamp techniques in solutions whose pH values ranged from 3.9 to 10.2. Buffer concentrations of 50 mM or greater were necessary to demonstrate the full effect of pH. In acidic solutions the axon underwent a variable depolarization, and both the sodium and potassium conductances were reversibly depressed with approximate pKa's of 4.8 and 4.4, respectively. The voltage dependence of GNa was only slightly altered by acidic conditions, whereas there occurred large shifts in GK along the voltage axis consistent with a substantial decrease in net negative surface charge in the vicinity of the K+ channels. The sodium and potassium activation rate constants were decreased by acidic conditions, but the results could not be described as a simple translation along the voltage axis."} {"id": "PMID:1255126", "title": "Signal transformation with pairing of sensory stimuli.", "content": "Rotation of the isolated nervous system of Hermissenda in a caudal orientation causes a synaptic hyperpolarization accompanied by elimination of impulse activity during the steady-state phase of type A but not type B photoreceptors' responses to light. Rotation of the isolated nervous system in a cephalic orientation causes a synaptic depolarization with increase of impulse activity during the steady-state phase of both type A and type B photoreceptors' responses to light. These effects of rotation on photorecptors are explained by known synaptic interactions. Sufficient redundancy is found to be provided by the neural organization of the visual system and its interaction with the statocyst to preserve much of the visual information in spite of signal transformation in specific photorecptors resulting from pairing of rotation with light.", "contents": "Signal transformation with pairing of sensory stimuli. Rotation of the isolated nervous system of Hermissenda in a caudal orientation causes a synaptic hyperpolarization accompanied by elimination of impulse activity during the steady-state phase of type A but not type B photoreceptors' responses to light. Rotation of the isolated nervous system in a cephalic orientation causes a synaptic depolarization with increase of impulse activity during the steady-state phase of both type A and type B photoreceptors' responses to light. These effects of rotation on photorecptors are explained by known synaptic interactions. Sufficient redundancy is found to be provided by the neural organization of the visual system and its interaction with the statocyst to preserve much of the visual information in spite of signal transformation in specific photorecptors resulting from pairing of rotation with light."} {"id": "PMID:1255127", "title": "The role of shear forces in arterial branching.", "content": "A new optimality principle for the branching angles of blood vessels in the cardiovascular system is proposed: the principle of minimum drag. The results are examined in the light of general observations and compared with those obtained from the principles of minimum work and minimum volume. It is shown that in some aspects the new principle is equally consistent with observations, and, in other aspects, it is perhaps more plausible than the other two principles.", "contents": "The role of shear forces in arterial branching. A new optimality principle for the branching angles of blood vessels in the cardiovascular system is proposed: the principle of minimum drag. The results are examined in the light of general observations and compared with those obtained from the principles of minimum work and minimum volume. It is shown that in some aspects the new principle is equally consistent with observations, and, in other aspects, it is perhaps more plausible than the other two principles."} {"id": "PMID:1255128", "title": "Effects of halides and bicarbonate on chloride transport in human red blood cells.", "content": "Chloride self-exchange was determined by measuring the rate of 36Cl efflux from human red blood cells at pH 7.2 (0 degrees C) in the presence of fluoride, bromide, iodide, and bicarbonate. The chloride concentration was varied between 10--400 mM and the concentration of other halides and bicarbonate between 10--300 mM. Chloride equilibrium flux showed saturation kinetics. The half-saturation constant increased and the maximum flux decreased in the presence of halides and bicarbonate: the inhibition kinetics were both competitive and noncompetitive. The competitive and the noncompetitive effects increased proportionately in the sequence: fluoride less than bromide less than iodide. The inhibitory action of bicarbonate was predominantly competitive. The noncompetitive effect of chloride (chloride self-inhibition) on chloride transport was less dominant at high inhibitor concentrations. Similarly, the noncompetitive action of the inhibitors was less dominant at high chloride concentrations. The results can be described by a carrier model with two anion binding sites: a transport site, and a second site which modifies the maximum transport rate. Binding to both types of sites increases proportionately in the sequence: fluoride less than chloride less than bromide less than iodide.", "contents": "Effects of halides and bicarbonate on chloride transport in human red blood cells. Chloride self-exchange was determined by measuring the rate of 36Cl efflux from human red blood cells at pH 7.2 (0 degrees C) in the presence of fluoride, bromide, iodide, and bicarbonate. The chloride concentration was varied between 10--400 mM and the concentration of other halides and bicarbonate between 10--300 mM. Chloride equilibrium flux showed saturation kinetics. The half-saturation constant increased and the maximum flux decreased in the presence of halides and bicarbonate: the inhibition kinetics were both competitive and noncompetitive. The competitive and the noncompetitive effects increased proportionately in the sequence: fluoride less than bromide less than iodide. The inhibitory action of bicarbonate was predominantly competitive. The noncompetitive effect of chloride (chloride self-inhibition) on chloride transport was less dominant at high inhibitor concentrations. Similarly, the noncompetitive action of the inhibitors was less dominant at high chloride concentrations. The results can be described by a carrier model with two anion binding sites: a transport site, and a second site which modifies the maximum transport rate. Binding to both types of sites increases proportionately in the sequence: fluoride less than chloride less than bromide less than iodide."} {"id": "PMID:1255129", "title": "Adaptation and facilitation in the barnacle photoreceptor.", "content": "The barnacle photoreceptor sensitivity may either decrease (light adaptation) or increase (facilitation) after exposure to a conditioning light. The balance between adaptation and facilitation is influenced by at least three factors: initial sensitivity state of the cell, external calcium concentration, and conditioning intensity. Cells of very high sensitivity show mainly adaptation, which appears only for higher conditioning intensities and is suppressed in low-calcium media. Less sensitive cells, or those whose sensitivity is reduced by injury or metabolic decay, exhibit facilitation, expecially in low-calcium media and at intermediate conditioning intensities. Both phenomena show recovery time-courses of seconds-to-minutes. Models are proposed which relate light adaptation, as previously suggested, to increased internal calcium concentration, and facilitation either to decreased internal calcium concentration or to decreased activation \"affinity\" of ion-channel-blocking sites.", "contents": "Adaptation and facilitation in the barnacle photoreceptor. The barnacle photoreceptor sensitivity may either decrease (light adaptation) or increase (facilitation) after exposure to a conditioning light. The balance between adaptation and facilitation is influenced by at least three factors: initial sensitivity state of the cell, external calcium concentration, and conditioning intensity. Cells of very high sensitivity show mainly adaptation, which appears only for higher conditioning intensities and is suppressed in low-calcium media. Less sensitive cells, or those whose sensitivity is reduced by injury or metabolic decay, exhibit facilitation, expecially in low-calcium media and at intermediate conditioning intensities. Both phenomena show recovery time-courses of seconds-to-minutes. Models are proposed which relate light adaptation, as previously suggested, to increased internal calcium concentration, and facilitation either to decreased internal calcium concentration or to decreased activation \"affinity\" of ion-channel-blocking sites."} {"id": "PMID:1255130", "title": "Phagocytosis and pinocytosis in Acanthamoeba castellanii.", "content": "Endocytotic activity of Acanthamoeba trophozoites attenuates once the cells enter stationary phase in liquid culture. Phagocytosis, monitored by the ingestion of polystyrene latex beads, essentially ceases and the uptake of [3H]inulin, known to be mediated by pinocytosis, is reduced by about half. The reduced pinocytotic activity of stationary-phase cells remains sensitive to respiratory inhibitors. Preincubation of stationary-phase cells in fresh growth medium for 1-5 h before the initiation of endocytosis has no effect on phagocytosis and only marginally increases pinocytosis. This impairment of ingestion, particularly of pinocytosis, may account for the reduced contractile vacuole activity known to characterize stationary-phase cells of this organism. The unequal responses of phagocytosis and pinocytosis to the onset of stationary-phase growth suggest that they are independent processes subject to different controls.", "contents": "Phagocytosis and pinocytosis in Acanthamoeba castellanii. Endocytotic activity of Acanthamoeba trophozoites attenuates once the cells enter stationary phase in liquid culture. Phagocytosis, monitored by the ingestion of polystyrene latex beads, essentially ceases and the uptake of [3H]inulin, known to be mediated by pinocytosis, is reduced by about half. The reduced pinocytotic activity of stationary-phase cells remains sensitive to respiratory inhibitors. Preincubation of stationary-phase cells in fresh growth medium for 1-5 h before the initiation of endocytosis has no effect on phagocytosis and only marginally increases pinocytosis. This impairment of ingestion, particularly of pinocytosis, may account for the reduced contractile vacuole activity known to characterize stationary-phase cells of this organism. The unequal responses of phagocytosis and pinocytosis to the onset of stationary-phase growth suggest that they are independent processes subject to different controls."} {"id": "PMID:1255131", "title": "Peptide utilization by Pseudomonas putida and Pseudomonas maltophilia.", "content": "Pseudomonas putida assimilates peptides and hydrolyses them with intracellular peptidases. Amino acid auxotrophs (his, trp, thr or met) grew on a variety of di- and tripeptides up to twice as slowly as with free amino acids. Pseudomonas putida has separate uptake systems for both dipeptides and oligopeptides (three or more residues). Although the dipeptide system transported a variety of structurally diverse dipeptides it did not transport peptides having either unprotonatable N-terminal amino groups, blocked C-terminal carboxyl groups, D-residues, three or more residues, N-methylated peptide bonds, or beta-amino acids. Oligopeptide uptake lacked amino acid side-chain specificity, required a free N-terminal L-residue and had an upper size limit. Glycylglycyl-D,L-p-fluorophenylalanine inhibited growth of P. putida. Uptake of glycylglycyl[I-14C]alanine was rapid and inhibited by 2,4-dinitrophenol. Both dipeptide and oligopeptide uptake were constitutive. Dipeptides competed with oligopeptides for oligopeptide uptake, but oligopeptides did not compete in the dipeptide system. Final bacterial yields were 5 to 10 times greater when P. putida his was grown on histidyl di- or tripeptides rather than on free histidine because the histidyl residue was protected from catabolism by L-histidine ammonia-lyase. Methionine peptides could satisfy the methionine requirements of P. maltophilia. Generation times on glycylmethionine and glycylmethionylglycine were equal to those obtained with free methionine. Methionylglycylmethionylmethionine gave a generation time twice that of free methionine. Growth of P. maltophilia was inhibited by glycylglycyl-D,L-p-fluorophenylalanine.", "contents": "Peptide utilization by Pseudomonas putida and Pseudomonas maltophilia. Pseudomonas putida assimilates peptides and hydrolyses them with intracellular peptidases. Amino acid auxotrophs (his, trp, thr or met) grew on a variety of di- and tripeptides up to twice as slowly as with free amino acids. Pseudomonas putida has separate uptake systems for both dipeptides and oligopeptides (three or more residues). Although the dipeptide system transported a variety of structurally diverse dipeptides it did not transport peptides having either unprotonatable N-terminal amino groups, blocked C-terminal carboxyl groups, D-residues, three or more residues, N-methylated peptide bonds, or beta-amino acids. Oligopeptide uptake lacked amino acid side-chain specificity, required a free N-terminal L-residue and had an upper size limit. Glycylglycyl-D,L-p-fluorophenylalanine inhibited growth of P. putida. Uptake of glycylglycyl[I-14C]alanine was rapid and inhibited by 2,4-dinitrophenol. Both dipeptide and oligopeptide uptake were constitutive. Dipeptides competed with oligopeptides for oligopeptide uptake, but oligopeptides did not compete in the dipeptide system. Final bacterial yields were 5 to 10 times greater when P. putida his was grown on histidyl di- or tripeptides rather than on free histidine because the histidyl residue was protected from catabolism by L-histidine ammonia-lyase. Methionine peptides could satisfy the methionine requirements of P. maltophilia. Generation times on glycylmethionine and glycylmethionylglycine were equal to those obtained with free methionine. Methionylglycylmethionylmethionine gave a generation time twice that of free methionine. Growth of P. maltophilia was inhibited by glycylglycyl-D,L-p-fluorophenylalanine."} {"id": "PMID:1255132", "title": "Intracellular peptide hydrolysis by Pseudomonas putida and Pseudomonas maltophilia.", "content": "Amino acids liberated by peptidase hydrolysis of di- and oligopeptides by Pseudomonas putida were measured by trinitrobenzenesulphonate assay and high voltage electrophoresis or paper chromatography followed by ninhydrin spray. Intact bacteria or periplasmic contents released by lysozyme treatment did not hydrolyse peptides. Subcellular fractionation showed that glycylmethionine peptidase activity was cytoplasmic. This enzyme had a Km of 2 mM, and was stimulated fivefold by I mM-Co2+. Crude peptidase extract did not cleave peptides with D-residues, acylated N-terminal amino groups or N-methylated peptide bonds but otherwise showed a wide specificity. Di- or tripeptides with blocked C-terminus were hydrolysed. Leucylleucine (12 mM) and leucylglycylglycine (10 mM) did not compete with glycylmethionine (1-2 mM) and glycylmethionylglycine (1-0 mM), respectively, for hydrolysis. Pseudomonas maltophilia also contained peptidase activity (0-84 mumol amino acid released from glycylmethionylglycine/min/mg protein). Peptidases of both P. putida and P. maltophilia were constitutive.", "contents": "Intracellular peptide hydrolysis by Pseudomonas putida and Pseudomonas maltophilia. Amino acids liberated by peptidase hydrolysis of di- and oligopeptides by Pseudomonas putida were measured by trinitrobenzenesulphonate assay and high voltage electrophoresis or paper chromatography followed by ninhydrin spray. Intact bacteria or periplasmic contents released by lysozyme treatment did not hydrolyse peptides. Subcellular fractionation showed that glycylmethionine peptidase activity was cytoplasmic. This enzyme had a Km of 2 mM, and was stimulated fivefold by I mM-Co2+. Crude peptidase extract did not cleave peptides with D-residues, acylated N-terminal amino groups or N-methylated peptide bonds but otherwise showed a wide specificity. Di- or tripeptides with blocked C-terminus were hydrolysed. Leucylleucine (12 mM) and leucylglycylglycine (10 mM) did not compete with glycylmethionine (1-2 mM) and glycylmethionylglycine (1-0 mM), respectively, for hydrolysis. Pseudomonas maltophilia also contained peptidase activity (0-84 mumol amino acid released from glycylmethionylglycine/min/mg protein). Peptidases of both P. putida and P. maltophilia were constitutive."} {"id": "PMID:1255133", "title": "The influence of culture conditions on carotenogenesis in Streptococcus faecium UNH564P.", "content": "The growth of Streptococcus faecium UNH564P and its production of triterpenoid carotenoids under a variety of culture conditions were examined. Total extractable cell lipid and carotenoid levels increased with culture age and paralleled the growth curve of the bacterium. Variations of the medium glucose concentration produced significant changes in both cell growth and carotenoid production, with the xanthophyll content decreasing at high glucose concentrations. Carotenoid degradation products were found in highly aerated cultures although a high glucose concentration appeared to have a sparing effect on oxidative degradation. Culture age appeared to have little effect on carotene:xanthophyll ratios. The significance of the production of total and individual carotenoids under the various culture conditions is discussed and related to a postulated scheme of triterpenoid carotenoid biosynthesis in the organism.", "contents": "The influence of culture conditions on carotenogenesis in Streptococcus faecium UNH564P. The growth of Streptococcus faecium UNH564P and its production of triterpenoid carotenoids under a variety of culture conditions were examined. Total extractable cell lipid and carotenoid levels increased with culture age and paralleled the growth curve of the bacterium. Variations of the medium glucose concentration produced significant changes in both cell growth and carotenoid production, with the xanthophyll content decreasing at high glucose concentrations. Carotenoid degradation products were found in highly aerated cultures although a high glucose concentration appeared to have a sparing effect on oxidative degradation. Culture age appeared to have little effect on carotene:xanthophyll ratios. The significance of the production of total and individual carotenoids under the various culture conditions is discussed and related to a postulated scheme of triterpenoid carotenoid biosynthesis in the organism."} {"id": "PMID:1255135", "title": "Measurement of virus antigens on the surface of HeLa cells persistently infected with wild type and vaccine strains of measles virus by radioimmune assay.", "content": "Persistent states of measles virus infection have been established in HeLa cells by using Edmonston strain virus and two types of measles virus vaccine (M-VAC and Schwarz). The absolute amount of surface viral antigens expressed on these cells infected separately with the three viruses has been assessed by a newly developed method which employs [125I]-labelled Fab fragments of immunoglobulin G (IgG) from immune human sera. This method was used to determine the level of viral antigenic expression on acutely infected HeLa cells harvested at a time when 95 to 100% of cells could be lysed by antiviral antibody and complement. From our data, more than 1 X 10(6) antibody molecules must bind to each cell infected with measles virus before complement dependent lysis can occur in a homologous test system. Persistently infected cells bind 2 to 3 times less antibody than acutely infected cells and correspondingly exhibit less susceptibility to humorally-mediated immune lysis.", "contents": "Measurement of virus antigens on the surface of HeLa cells persistently infected with wild type and vaccine strains of measles virus by radioimmune assay. Persistent states of measles virus infection have been established in HeLa cells by using Edmonston strain virus and two types of measles virus vaccine (M-VAC and Schwarz). The absolute amount of surface viral antigens expressed on these cells infected separately with the three viruses has been assessed by a newly developed method which employs [125I]-labelled Fab fragments of immunoglobulin G (IgG) from immune human sera. This method was used to determine the level of viral antigenic expression on acutely infected HeLa cells harvested at a time when 95 to 100% of cells could be lysed by antiviral antibody and complement. From our data, more than 1 X 10(6) antibody molecules must bind to each cell infected with measles virus before complement dependent lysis can occur in a homologous test system. Persistently infected cells bind 2 to 3 times less antibody than acutely infected cells and correspondingly exhibit less susceptibility to humorally-mediated immune lysis."} {"id": "PMID:1255136", "title": "The replication of rodent parvovirus X14.", "content": "The replication of rodent parvovirus X14 DNA has been studied in rat embryo tissue culture cells. Virus DNA was isolated from I M-NaCl-SDS-pronase supernatant fluids from 24 h after infection. The majority of this DNA was 1-7 mum in length and double-stranded, indicating that it was an intermediate in the replication cycle of this single-stranded DNA virus. Single-stranded DNA of equivalent length was isolated directly from X14 virions. The buoyant density of this DNA was 1-728 g/ml whereas the double-stranded form banded at 1-714 g/ml in caesium chloride gradients. Difficulties in detecting significant amounts of single-stranded viral DNA directly from infected cells would appear to indicate that progeny single-stranded DNA is rapidly encapsidated after synthesis.", "contents": "The replication of rodent parvovirus X14. The replication of rodent parvovirus X14 DNA has been studied in rat embryo tissue culture cells. Virus DNA was isolated from I M-NaCl-SDS-pronase supernatant fluids from 24 h after infection. The majority of this DNA was 1-7 mum in length and double-stranded, indicating that it was an intermediate in the replication cycle of this single-stranded DNA virus. Single-stranded DNA of equivalent length was isolated directly from X14 virions. The buoyant density of this DNA was 1-728 g/ml whereas the double-stranded form banded at 1-714 g/ml in caesium chloride gradients. Difficulties in detecting significant amounts of single-stranded viral DNA directly from infected cells would appear to indicate that progeny single-stranded DNA is rapidly encapsidated after synthesis."} {"id": "PMID:1255137", "title": "Some cognitive, behavioral and personality correlates of maturity of moral judgment.", "content": "This study was designed to test the hypothesis that maturity of moral judgment is related to moral behavior and to certain personality characteristics. The Ss, 33 fifth grade boys (approximately 10 1/2-years of age), were given the Kohlberg test of moral judgment, and scores on this test were related to a measure of general intelligence, moral conduct as judged by peers (sociometric nominations), honesty in a structured test, and certain personality variables. Maturity of moral judgment was found to be significantly correlated with general cognitive ability (intelligence test performance) and, even with intelligence partialed out, with resistance to temptation, reputation for being concerned with the welfare of others, self-confidence, and security in social relationships with peers.", "contents": "Some cognitive, behavioral and personality correlates of maturity of moral judgment. This study was designed to test the hypothesis that maturity of moral judgment is related to moral behavior and to certain personality characteristics. The Ss, 33 fifth grade boys (approximately 10 1/2-years of age), were given the Kohlberg test of moral judgment, and scores on this test were related to a measure of general intelligence, moral conduct as judged by peers (sociometric nominations), honesty in a structured test, and certain personality variables. Maturity of moral judgment was found to be significantly correlated with general cognitive ability (intelligence test performance) and, even with intelligence partialed out, with resistance to temptation, reputation for being concerned with the welfare of others, self-confidence, and security in social relationships with peers."} {"id": "PMID:1255138", "title": "Components of school anxiety: developmental trends and sex differences.", "content": "Dunn's School Anxiety Questionnaire was administered to 104 third through eighth graders (Study I) and 122 eighth graders (Study II). Significant decrements in anxiety with increasing age were found for worry (but not emotionality), report card anxiety, and failure anxiety. In Study I girls scored significantly higher than boys on emotionality (but not worry) and test anxiety. Sex differences were greater in Study II, girls scoring consistently higher. In Study II a worry-emotionality questionnaire administered immediately preceding a final examination correlated highly with School Anxiety Questionnaire scores. Results are taken as generally supportive of the multidimensional approach to the study of school anxiety.", "contents": "Components of school anxiety: developmental trends and sex differences. Dunn's School Anxiety Questionnaire was administered to 104 third through eighth graders (Study I) and 122 eighth graders (Study II). Significant decrements in anxiety with increasing age were found for worry (but not emotionality), report card anxiety, and failure anxiety. In Study I girls scored significantly higher than boys on emotionality (but not worry) and test anxiety. Sex differences were greater in Study II, girls scoring consistently higher. In Study II a worry-emotionality questionnaire administered immediately preceding a final examination correlated highly with School Anxiety Questionnaire scores. Results are taken as generally supportive of the multidimensional approach to the study of school anxiety."} {"id": "PMID:1255139", "title": "The effects of locus control and field independence-dependence on moral reasoning.", "content": "This study investigated whether stages of moral reasoning vary as a function of locus of control and degree of field independence. Results, based upon 36 female undergraduates, indicated a tendency for both variables to provide some prediction of morality status when used conjointly. This derived from the fact that field independent-internal Ss has disproportionately higher scores on Kohlberg's Moral Judgment Interview than field dependent-internal, field independent-external, and field dependent-external Ss. The latter showed no appreciable differences among them.", "contents": "The effects of locus control and field independence-dependence on moral reasoning. This study investigated whether stages of moral reasoning vary as a function of locus of control and degree of field independence. Results, based upon 36 female undergraduates, indicated a tendency for both variables to provide some prediction of morality status when used conjointly. This derived from the fact that field independent-internal Ss has disproportionately higher scores on Kohlberg's Moral Judgment Interview than field dependent-internal, field independent-external, and field dependent-external Ss. The latter showed no appreciable differences among them."} {"id": "PMID:1255140", "title": "Conservation of length and the development of a size concept.", "content": "The influence of the ability to conserve length in the development of a size concept was investigated in a series of two experiments. The inability to conserve length influences the perceptual bias of young children using the linear vertical dimension of objects as a salient cue in a paired comparison task when stimulus objects do not share a common baseline. When both stimulus position and attributed functional direction are involved, the latter is more influential in serving an orienting function. Sex differences suggest that females are more field dependent than males in the use of the vertical linear dimension as a cue in the judgment of \"bigger\" in a paired comparison task.", "contents": "Conservation of length and the development of a size concept. The influence of the ability to conserve length in the development of a size concept was investigated in a series of two experiments. The inability to conserve length influences the perceptual bias of young children using the linear vertical dimension of objects as a salient cue in a paired comparison task when stimulus objects do not share a common baseline. When both stimulus position and attributed functional direction are involved, the latter is more influential in serving an orienting function. Sex differences suggest that females are more field dependent than males in the use of the vertical linear dimension as a cue in the judgment of \"bigger\" in a paired comparison task."} {"id": "PMID:1255141", "title": "Motivational effects of hunger on time estimation and delay of gratification in obese and nonobese boys.", "content": "Time estimates and ability to delay gratification of obese and nonobese boys were compared by a 2x2x2 factorial experiment in which hunger and edibility of incentives were manipulated. Hunger did not affect estimates of the obese boys, while it significantly shortened estimates made by the nonobese boys when the hunger drive was made either specific or nonspecific by varying incentive conditions. Although estimates of the nonobese boys were significantly shorter in the edible than nonedible incentive condition, edibility of incentives did not affect the estiamtes of the obese, suggesting a general rather than food-specific arousal in the nonobese and a general lack of response to internal cues in the obese. Immediate rewards were chosen significantly more often by obese than nonobese Ss. However, delay gratification in both obese and nonobese was unaffected by the hunger and edibility of incentive manipulations. This was attributed to uncontrolled cognitive variables.", "contents": "Motivational effects of hunger on time estimation and delay of gratification in obese and nonobese boys. Time estimates and ability to delay gratification of obese and nonobese boys were compared by a 2x2x2 factorial experiment in which hunger and edibility of incentives were manipulated. Hunger did not affect estimates of the obese boys, while it significantly shortened estimates made by the nonobese boys when the hunger drive was made either specific or nonspecific by varying incentive conditions. Although estimates of the nonobese boys were significantly shorter in the edible than nonedible incentive condition, edibility of incentives did not affect the estiamtes of the obese, suggesting a general rather than food-specific arousal in the nonobese and a general lack of response to internal cues in the obese. Immediate rewards were chosen significantly more often by obese than nonobese Ss. However, delay gratification in both obese and nonobese was unaffected by the hunger and edibility of incentive manipulations. This was attributed to uncontrolled cognitive variables."} {"id": "PMID:1255142", "title": "Comparative levels of creative ability in black and white college students.", "content": "Eighty-seven black, educational psychology students from three intact, randomly selected classes at Tennessee State University were compared to ninety-four white, educational phychology students from three intact, randomly selected classes at the University of Tennessee on Torrance's Unusual Uses and Ask and Guess activities. No differences were found on the frequency of flexibility measures of either activity. No attempt was made to examine the results on this \"Level II\" mental ability measure on any variable except race. There were no differences based on race.", "contents": "Comparative levels of creative ability in black and white college students. Eighty-seven black, educational psychology students from three intact, randomly selected classes at Tennessee State University were compared to ninety-four white, educational phychology students from three intact, randomly selected classes at the University of Tennessee on Torrance's Unusual Uses and Ask and Guess activities. No differences were found on the frequency of flexibility measures of either activity. No attempt was made to examine the results on this \"Level II\" mental ability measure on any variable except race. There were no differences based on race."} {"id": "PMID:1255144", "title": "Visual discrimination in the Mongolian gerbil (Meriones unguiculatus) as a function of age.", "content": "Ten young (8 weeks) and 10 old (26 weeks) male gerbils were tested for the acquisition of a visual discrimination task. Ss were given 10 daily six-trial sessions in a T-maze with a food reinforcement being associated with horizontal or vertical stripes. The older Ss failed to learn the discrimination habit, and the young Ss steadily improved over the 10 sessions.", "contents": "Visual discrimination in the Mongolian gerbil (Meriones unguiculatus) as a function of age. Ten young (8 weeks) and 10 old (26 weeks) male gerbils were tested for the acquisition of a visual discrimination task. Ss were given 10 daily six-trial sessions in a T-maze with a food reinforcement being associated with horizontal or vertical stripes. The older Ss failed to learn the discrimination habit, and the young Ss steadily improved over the 10 sessions."} {"id": "PMID:1255145", "title": "The effect of visual angle orientation on perceived oscillatory motion.", "content": "The present experiment examined the effect of independently varying central, vertical, and horizontal visual angles (CVVA, CHVA) on proportion of perceived oscillations with rotating trapezoids. Twenty-five female undergraduates served as Ss. Diminution of the CHVA proved most effective in increasing oscillatory perception (p less than .01), although perceived oscillation was found to be inversely proportional to CVVA and CHVA (p less than .001). The data indicate that Os primarily rely on perceptual cues determined by the horizontal dimension of a trapezoid. When cue discriminability is reduced, the results suggest that O's perceptual response may be a function on individual differences in cue thresholds, and/or response criteria.", "contents": "The effect of visual angle orientation on perceived oscillatory motion. The present experiment examined the effect of independently varying central, vertical, and horizontal visual angles (CVVA, CHVA) on proportion of perceived oscillations with rotating trapezoids. Twenty-five female undergraduates served as Ss. Diminution of the CHVA proved most effective in increasing oscillatory perception (p less than .01), although perceived oscillation was found to be inversely proportional to CVVA and CHVA (p less than .001). The data indicate that Os primarily rely on perceptual cues determined by the horizontal dimension of a trapezoid. When cue discriminability is reduced, the results suggest that O's perceptual response may be a function on individual differences in cue thresholds, and/or response criteria."} {"id": "PMID:1255146", "title": "Psychological adaptation to jejunoileal bypass for morbid obesity.", "content": "Psychological adaptation to jejunoileal bypass procedures in 34 morbidly obese patients was evaluated preoperatively and followed postoperatively for an average of 23 months. Preoperative emotional disturbances were mainly those of mild personality disorders with passive-aggressive, passive-dependent, and emotionally immature traits. Following discharge from the hospital, nine patients (or 24 per cent) developed psychiatric difficulties, characterized by either increased neurotic symptoms and interpersonal problems, or the emergence of psychosis. Male patients and those with the greatest weight loss were statistically more likely to have psychiatric complications. The remaining patients expressed satisfaction with the operation, noted relief from the burden of dieting, experienced less excitement associated with eating, and felt more self-confident and hopeful.", "contents": "Psychological adaptation to jejunoileal bypass for morbid obesity. Psychological adaptation to jejunoileal bypass procedures in 34 morbidly obese patients was evaluated preoperatively and followed postoperatively for an average of 23 months. Preoperative emotional disturbances were mainly those of mild personality disorders with passive-aggressive, passive-dependent, and emotionally immature traits. Following discharge from the hospital, nine patients (or 24 per cent) developed psychiatric difficulties, characterized by either increased neurotic symptoms and interpersonal problems, or the emergence of psychosis. Male patients and those with the greatest weight loss were statistically more likely to have psychiatric complications. The remaining patients expressed satisfaction with the operation, noted relief from the burden of dieting, experienced less excitement associated with eating, and felt more self-confident and hopeful."} {"id": "PMID:1255147", "title": "Evaluation of the initial interview in a walk-in clinic. The patient's perspective on a \"customer approach\".", "content": "There have been different models on how to conduct the initial psychiatric interview in a walk-in clinic. A \"customer approach\" has been developed which stresses: a) eliciting and understanding the requests that patients have regarding how they hope to be helped; and b) negotiating a treatment plan with the patients. We evaluated this customer approach from the perspective of the patient. The first hypothesis was supported. The patient's perception of the clinician's utilization of the customer approach correlated positively and substantially with measures of outcome, especially feeling satisfied and helped. The second hypothesis was also supported. Utilization of the customer approach continued to correlate positively and substantially with outcome even when patients did not get the disposition originally wanted. We discussed the clinical significance of the customer approach especially in regard to patient objectives in the initial interview--a treatment plan vs. symptom relief.", "contents": "Evaluation of the initial interview in a walk-in clinic. The patient's perspective on a \"customer approach\". There have been different models on how to conduct the initial psychiatric interview in a walk-in clinic. A \"customer approach\" has been developed which stresses: a) eliciting and understanding the requests that patients have regarding how they hope to be helped; and b) negotiating a treatment plan with the patients. We evaluated this customer approach from the perspective of the patient. The first hypothesis was supported. The patient's perception of the clinician's utilization of the customer approach correlated positively and substantially with measures of outcome, especially feeling satisfied and helped. The second hypothesis was also supported. Utilization of the customer approach continued to correlate positively and substantially with outcome even when patients did not get the disposition originally wanted. We discussed the clinical significance of the customer approach especially in regard to patient objectives in the initial interview--a treatment plan vs. symptom relief."} {"id": "PMID:1255148", "title": "Electrodermal response configuration as a function of rated psychopathology in children.", "content": "Electrodermally labile children of schizophrenic, manic-depressive, and normal parents were identified as either uniphasic or biphasic responders, in each of three phases of a psychophysiological experiment. Psychological disturbance ratings, based upon test protocols, were determined independently. Analysis of the relationship between electrodermal response configuration and rated psychological pathology showed that biphasic responders were evaluated as more disturbed than uniphasic responders. The results were interpreted within a framework provided by Edelberg's work on the information content of the electrodermal recovery limb, and were seen as relevant to notions regarding schizophrenic information processing. It was hypothesized that in this situation, uniphasic responding reflected an adaptive defense against stimuli perceived as potentially threatening, whereas biphasic responding indicated overprocessing and inappropriate goal orientation.", "contents": "Electrodermal response configuration as a function of rated psychopathology in children. Electrodermally labile children of schizophrenic, manic-depressive, and normal parents were identified as either uniphasic or biphasic responders, in each of three phases of a psychophysiological experiment. Psychological disturbance ratings, based upon test protocols, were determined independently. Analysis of the relationship between electrodermal response configuration and rated psychological pathology showed that biphasic responders were evaluated as more disturbed than uniphasic responders. The results were interpreted within a framework provided by Edelberg's work on the information content of the electrodermal recovery limb, and were seen as relevant to notions regarding schizophrenic information processing. It was hypothesized that in this situation, uniphasic responding reflected an adaptive defense against stimuli perceived as potentially threatening, whereas biphasic responding indicated overprocessing and inappropriate goal orientation."} {"id": "PMID:1255149", "title": "Anxiety neurosis: a 5-year follow-up.", "content": "Fifty-seven patients who were seen on a psychiatric consultation service and who met criteria for the diagnosis of anxiety neurosis were followed up after 5 years. These patients presented symptoms from a variety of organ systems and appeared typical of anxiety neurotics seen in general medical practice. A favorable outcome was demonstrated in 67 per cent who were either recovered or mildly impaired. Women showed a more favorable outcome than men. Among men, age at the time of consultation was positively correlated with the degree of impairment after 5 years.", "contents": "Anxiety neurosis: a 5-year follow-up. Fifty-seven patients who were seen on a psychiatric consultation service and who met criteria for the diagnosis of anxiety neurosis were followed up after 5 years. These patients presented symptoms from a variety of organ systems and appeared typical of anxiety neurotics seen in general medical practice. A favorable outcome was demonstrated in 67 per cent who were either recovered or mildly impaired. Women showed a more favorable outcome than men. Among men, age at the time of consultation was positively correlated with the degree of impairment after 5 years."} {"id": "PMID:1255150", "title": "Token economies in institutional settings. Historical, political, deprivation, ethical, and generalization issues.", "content": "The use of the token economy in institutional settings is examined in light of historical, political, deprivation, ethical, and generalization issues. The major points may be summarized as follows. a) The token economy may be viewed as a palliative measure to prevent the incredibly regressive effects of institutionalization. b) To achieve control in token programs in many \"total institutions,\" an artificial state of deprivation must be achieved. c) Generalization of behaviors into the natural environment following the patient's stay in a token economy program should not be taken for granted. d) What the patient learns in a token economic system may not be what the token economy's program director probably intends.", "contents": "Token economies in institutional settings. Historical, political, deprivation, ethical, and generalization issues. The use of the token economy in institutional settings is examined in light of historical, political, deprivation, ethical, and generalization issues. The major points may be summarized as follows. a) The token economy may be viewed as a palliative measure to prevent the incredibly regressive effects of institutionalization. b) To achieve control in token programs in many \"total institutions,\" an artificial state of deprivation must be achieved. c) Generalization of behaviors into the natural environment following the patient's stay in a token economy program should not be taken for granted. d) What the patient learns in a token economic system may not be what the token economy's program director probably intends."} {"id": "PMID:1255151", "title": "Clinical and psychological test findings in cerebral dyspraxia associated with hemodialysis.", "content": "Cerebral dyspraxia associated with hemodialysis is a progressive, fatal syndrome. Patients suffer from a combination of psychiatric and neurological signs and symptoms. Psychiatric manifestations include anxiety, depression, paranoid ideation, and a progressive dementia with impaired concentration, decreased memory, personality changes, and hallucinations. Neurological findings include deliberate speech, stuttering, dysarthria, dyspraxia of speech and movement, tremulousness, myoclonic activity, asterixis, and seizures. These symptoms are aggravated during and immediately following dialysis. Patients usually die within 6 months of its onset. The etiology is unknown. Treatment efforts have failed to reverse its course. Recognition of this syndrome is highlighted so that informed, critical decisions can be made as to whether to continue dialysis therapy.", "contents": "Clinical and psychological test findings in cerebral dyspraxia associated with hemodialysis. Cerebral dyspraxia associated with hemodialysis is a progressive, fatal syndrome. Patients suffer from a combination of psychiatric and neurological signs and symptoms. Psychiatric manifestations include anxiety, depression, paranoid ideation, and a progressive dementia with impaired concentration, decreased memory, personality changes, and hallucinations. Neurological findings include deliberate speech, stuttering, dysarthria, dyspraxia of speech and movement, tremulousness, myoclonic activity, asterixis, and seizures. These symptoms are aggravated during and immediately following dialysis. Patients usually die within 6 months of its onset. The etiology is unknown. Treatment efforts have failed to reverse its course. Recognition of this syndrome is highlighted so that informed, critical decisions can be made as to whether to continue dialysis therapy."} {"id": "PMID:1255152", "title": "Marital discord, sexual problems, and depression.", "content": "Systematic studies of relationships among depression, sexual function, and martial discord in hemodialysis patients and their spouses arelacking; existing studies focus upon only one of these three topics, or deal with patient or spouse as individuals rather than as a couple. We studied 17 chronic, medically stable hemodialysis patients and their husbands or wives. Although couples rated their degree of marital discord as low, the investigators rated it as high, based on the number and type of specific problems reported by the couple. The couples' evaluation may not represent denial, as has been commonly assumed. Instead their evaluation may imply that the disease and its treatment overshadow marital problems, even though couples recognize and react to these problems. Couples showed a high prevalence of sexual problems--in terms of overall satisfaction, frequency of intercourse, and specific dysfunctional symptoms (difficulty becoming excited, maintaining excitement, or having orgasm). We found a strong relationship between severity of depression and severity of sexual dysfunction in patients, but not in their mates. No strong relationship existed between a patient's depression score and marital discord, although spouses showed a trend toward correlation between severity of depression and martial discord. Younger couples, especially, seem not to want intercourse when severe martial discord exists. Patients' depression scores were comparable to thoseof psychiatric patients, while spouses' depression scores resembled those of normals. While psychosocial phenomena such as marital discord, sexual dysfunction, and depression are clear, causal chains are not. Despite disadvantages inherent in using questionnaires, short, self-administered, easily scored instruments may elicit problems with sex, marriage, and mood which might otherwise be overlooked by caretaking personnel.", "contents": "Marital discord, sexual problems, and depression. Systematic studies of relationships among depression, sexual function, and martial discord in hemodialysis patients and their spouses arelacking; existing studies focus upon only one of these three topics, or deal with patient or spouse as individuals rather than as a couple. We studied 17 chronic, medically stable hemodialysis patients and their husbands or wives. Although couples rated their degree of marital discord as low, the investigators rated it as high, based on the number and type of specific problems reported by the couple. The couples' evaluation may not represent denial, as has been commonly assumed. Instead their evaluation may imply that the disease and its treatment overshadow marital problems, even though couples recognize and react to these problems. Couples showed a high prevalence of sexual problems--in terms of overall satisfaction, frequency of intercourse, and specific dysfunctional symptoms (difficulty becoming excited, maintaining excitement, or having orgasm). We found a strong relationship between severity of depression and severity of sexual dysfunction in patients, but not in their mates. No strong relationship existed between a patient's depression score and marital discord, although spouses showed a trend toward correlation between severity of depression and martial discord. Younger couples, especially, seem not to want intercourse when severe martial discord exists. Patients' depression scores were comparable to thoseof psychiatric patients, while spouses' depression scores resembled those of normals. While psychosocial phenomena such as marital discord, sexual dysfunction, and depression are clear, causal chains are not. Despite disadvantages inherent in using questionnaires, short, self-administered, easily scored instruments may elicit problems with sex, marriage, and mood which might otherwise be overlooked by caretaking personnel."} {"id": "PMID:1255153", "title": "The fate of the untreated alcoholic. Toward a natural history of the disorder.", "content": "Eighty-three male alcoholics were administered a structured interview when they appeared at a large general hospital for treatment of a variety of disorders. These represent 83 consecutive cases. None received treatment aside from brief \"drying-out\" but all were accepted as participants in a research program. Seventy-three (88 per cent of the sample) were located for a 3-year follow-up; five of these were not seen at the 1-year follow-up, and 10 were known to be dead. This paper focuses on 58 of the alcoholics who were seen at all three evaluations, and the 10 who were known dead. The data are presented as indicating the long term results of, at best, a mild or minimal intervention with male alcoholics. A small, but significant improvement was noted on several life-adjustment scales between the initial and 1-year evaluation (OYE), but no further improvement was seen between OYE and the 3-year evaluation (TYE); 19 percent were abstinent for 1 year and 10 per cent for the full 3-year period. The best predictor of TYE abstinence was OYE abstinence, but only for the extremes, i.e., no abstinence or total abstinence. Abstinence success was also related to a tendency to use community resources, lower number of mental hospitalizations, higher occupational status, higher global rating and, curiously, lower interpersonal adjustment rating. The group using Alcoholics Anonymous showed no better outcome than the group using no community resources at all. The mortality rate was 12 per cent over the 3 years or slightly more than 4 per cent a year. The suicide rate was about 4 per cent over the 3 years. The ratings for those dying showed a pattern of more admitted drunken arrests and heavy recent drinking superimposed on lighter overall drinking for the past year. The study demonstrates that even untreated alcoholics can be traced and effective follow-up studies completed. Results also indicate that over long time periods and left to their own devices, many alcoholics do seek out some form of help. But such assistance tends not to be sustained or intensive and a good portion of it is nonprofessional and nonmedical. Moreover, a surprisingly substantial number (31 per cent) of hospital-identified alcoholics apparently neither seek out nor receive any help at all after their initial identification; yet their self-reported life-adjustment ratings do not differ significantly from those who do seek help. The no-help receivers may be the most critical group of all to follow, as they are trule untreated. It would be important to determine how consistent in fact they are in their avoidance of help, what accounts for that behavior, and whether their ultimate fate is different from those who regularly seek assistance.", "contents": "The fate of the untreated alcoholic. Toward a natural history of the disorder. Eighty-three male alcoholics were administered a structured interview when they appeared at a large general hospital for treatment of a variety of disorders. These represent 83 consecutive cases. None received treatment aside from brief \"drying-out\" but all were accepted as participants in a research program. Seventy-three (88 per cent of the sample) were located for a 3-year follow-up; five of these were not seen at the 1-year follow-up, and 10 were known to be dead. This paper focuses on 58 of the alcoholics who were seen at all three evaluations, and the 10 who were known dead. The data are presented as indicating the long term results of, at best, a mild or minimal intervention with male alcoholics. A small, but significant improvement was noted on several life-adjustment scales between the initial and 1-year evaluation (OYE), but no further improvement was seen between OYE and the 3-year evaluation (TYE); 19 percent were abstinent for 1 year and 10 per cent for the full 3-year period. The best predictor of TYE abstinence was OYE abstinence, but only for the extremes, i.e., no abstinence or total abstinence. Abstinence success was also related to a tendency to use community resources, lower number of mental hospitalizations, higher occupational status, higher global rating and, curiously, lower interpersonal adjustment rating. The group using Alcoholics Anonymous showed no better outcome than the group using no community resources at all. The mortality rate was 12 per cent over the 3 years or slightly more than 4 per cent a year. The suicide rate was about 4 per cent over the 3 years. The ratings for those dying showed a pattern of more admitted drunken arrests and heavy recent drinking superimposed on lighter overall drinking for the past year. The study demonstrates that even untreated alcoholics can be traced and effective follow-up studies completed. Results also indicate that over long time periods and left to their own devices, many alcoholics do seek out some form of help. But such assistance tends not to be sustained or intensive and a good portion of it is nonprofessional and nonmedical. Moreover, a surprisingly substantial number (31 per cent) of hospital-identified alcoholics apparently neither seek out nor receive any help at all after their initial identification; yet their self-reported life-adjustment ratings do not differ significantly from those who do seek help. The no-help receivers may be the most critical group of all to follow, as they are trule untreated. It would be important to determine how consistent in fact they are in their avoidance of help, what accounts for that behavior, and whether their ultimate fate is different from those who regularly seek assistance."} {"id": "PMID:1255154", "title": "Some problems in the use of \"attitude\" and \"atmosphere\" scores as indicators of staff effectiveness in institutional treatment.", "content": "Most institutional investigators have used paper-and-pencil measures of staff attitudes, opinions, and beliefs about \"mental patients,\" \"mental illness,\" and treatment programs or \"atmosphere\" to describe individual staff or aggregate staff groups. Popular scales for assessing the latter staff characteristics are noted, with a review of empirical relationships to treatment effectiveness. A review of uncontrolled and frequently confounded variables related to both effectiveness, and attitude and atmosphere scales suggests that several problems exist in the use of such measures as even indirect assessments of staff activity. Specific questions are raised for investigation which need to be answered before such scales can provide more than \"demographic\" description of treatment staff. Direct assessment of actual staff behavior appears to be a better alternative for determining what staff do.", "contents": "Some problems in the use of \"attitude\" and \"atmosphere\" scores as indicators of staff effectiveness in institutional treatment. Most institutional investigators have used paper-and-pencil measures of staff attitudes, opinions, and beliefs about \"mental patients,\" \"mental illness,\" and treatment programs or \"atmosphere\" to describe individual staff or aggregate staff groups. Popular scales for assessing the latter staff characteristics are noted, with a review of empirical relationships to treatment effectiveness. A review of uncontrolled and frequently confounded variables related to both effectiveness, and attitude and atmosphere scales suggests that several problems exist in the use of such measures as even indirect assessments of staff activity. Specific questions are raised for investigation which need to be answered before such scales can provide more than \"demographic\" description of treatment staff. Direct assessment of actual staff behavior appears to be a better alternative for determining what staff do."} {"id": "PMID:1255155", "title": "Asymmetry of information processing in hallucinators and nonhallucinators.", "content": "In previous work we had developed evidence suggesting that hallucinating schizophrenics differ from nonhallucinators in the pattern of errors made in a shadowing task. Non hallucinators appeared to be less willing to guess when they were unsure. The errors of the hallucinators seemed more semantically elaborate. The experiment had not been designed to study these factors and the current experiment was conducted using a technique reported by Pisoni et al. These workers had studied normal Ss in an immediate recall task, using semantically well integrated (SWI) or poorly integrated (SPI) sentences. Pisoni et al. had shown that right ear presentation produced more accurate recall of SWI as compared to SPI sentences, whereas left ear presentation failed to discriminate these sentences. Utilizing the methods of Pisoni et al., we replicated their findings in a normal control group. The results from our hallucinating and nonhallucinating groups were different from each other, the nonhallucinators being less accurate, discriminating semantic integration level on left rather than right ear input, and making more fragmented errors. Little support could be found for attributing this pattern of performance to nonspecific aspects of the procedures. It appears that the nonhallucinators process information differently from hallucinators. These differences may reflect alterations in language development. It is speculated that such differences might be consistent with interference with the development of brain asymmetry.", "contents": "Asymmetry of information processing in hallucinators and nonhallucinators. In previous work we had developed evidence suggesting that hallucinating schizophrenics differ from nonhallucinators in the pattern of errors made in a shadowing task. Non hallucinators appeared to be less willing to guess when they were unsure. The errors of the hallucinators seemed more semantically elaborate. The experiment had not been designed to study these factors and the current experiment was conducted using a technique reported by Pisoni et al. These workers had studied normal Ss in an immediate recall task, using semantically well integrated (SWI) or poorly integrated (SPI) sentences. Pisoni et al. had shown that right ear presentation produced more accurate recall of SWI as compared to SPI sentences, whereas left ear presentation failed to discriminate these sentences. Utilizing the methods of Pisoni et al., we replicated their findings in a normal control group. The results from our hallucinating and nonhallucinating groups were different from each other, the nonhallucinators being less accurate, discriminating semantic integration level on left rather than right ear input, and making more fragmented errors. Little support could be found for attributing this pattern of performance to nonspecific aspects of the procedures. It appears that the nonhallucinators process information differently from hallucinators. These differences may reflect alterations in language development. It is speculated that such differences might be consistent with interference with the development of brain asymmetry."} {"id": "PMID:1255156", "title": "Disturbed preschizophrenics. Childhood symptoms in relation to adult outcome.", "content": "Adult outcome information was obtained for a sample of 45 males with a hospital diagnosis of schizophrenia. All cases had been treated at a child guidance clinic as children prior to the onset of schizophrenia as young adults. Refined outcome categories, which reflected the independent judgments of two clinical raters, led to the comparison of poor outcome with more favorable outcome cases in terms of antecedent characteristics. Five rationally derived childhood symptom scales were used. The psychotic scale was significantly related to poor outcome, while acting-out and aggressive symptom scales were related to more favorable adult outcomes. Neurotic and neurological scales were not predictive of outcome. Low childhood IQ and poor peer adjustment were significantly related to poor adult outcome. Sample limitations and comparison with results from other studies were discussed.", "contents": "Disturbed preschizophrenics. Childhood symptoms in relation to adult outcome. Adult outcome information was obtained for a sample of 45 males with a hospital diagnosis of schizophrenia. All cases had been treated at a child guidance clinic as children prior to the onset of schizophrenia as young adults. Refined outcome categories, which reflected the independent judgments of two clinical raters, led to the comparison of poor outcome with more favorable outcome cases in terms of antecedent characteristics. Five rationally derived childhood symptom scales were used. The psychotic scale was significantly related to poor outcome, while acting-out and aggressive symptom scales were related to more favorable adult outcomes. Neurotic and neurological scales were not predictive of outcome. Low childhood IQ and poor peer adjustment were significantly related to poor adult outcome. Sample limitations and comparison with results from other studies were discussed."} {"id": "PMID:1255157", "title": "Psychological effects of short term cerebellar stimulation in epilepsy.", "content": "The effects of short term cerebellar stimulation on integrative functions as measured by standardized psychological tests were studied. The patient group consisted of 12 epilepsy patients undergoing chronic cerebellar stimulation as treatment for intractable seizures. Three comparison groups included nonstimulated epilepsy patients, stimulated cerebral palsy patients, and stimulated stroke patients. Cerebellar stimulation resulted in some alterations in test performance. Improvements occurred from first to second test administration for both stimulated and nonstimulated subjects, as a probable practice effect. Short term stimulation of the cerebellar cortex does not result in apparent deficits. However, significant improvement in verbal output and in visual-motor performance occurred for the stimulated epilepsy group along with a small decrement in sustained concentration in a numerical task. Preliminary hypotheses were offered to explain the results.", "contents": "Psychological effects of short term cerebellar stimulation in epilepsy. The effects of short term cerebellar stimulation on integrative functions as measured by standardized psychological tests were studied. The patient group consisted of 12 epilepsy patients undergoing chronic cerebellar stimulation as treatment for intractable seizures. Three comparison groups included nonstimulated epilepsy patients, stimulated cerebral palsy patients, and stimulated stroke patients. Cerebellar stimulation resulted in some alterations in test performance. Improvements occurred from first to second test administration for both stimulated and nonstimulated subjects, as a probable practice effect. Short term stimulation of the cerebellar cortex does not result in apparent deficits. However, significant improvement in verbal output and in visual-motor performance occurred for the stimulated epilepsy group along with a small decrement in sustained concentration in a numerical task. Preliminary hypotheses were offered to explain the results."} {"id": "PMID:1255206", "title": "Craniopagus twins: surgical anatomy and embryology and their implications.", "content": "Craniopagus is of two types, partial and total. In the partial form the union is of limited extent, particularly as regards its depth, and separation can be expected to be followed by the survival of both children to lead normal lives. In the total form, of which three varieties can be recognized, the two brains can be regarded as lying within a single cranium and a series of gross intracranial abnormalities develops. These include deformity of the skull base, deformity and displacement of the cerebrum, and a gross circulatory abnormality. It is considered that these and other abnormalities, unlike the primary defect, which is defined, are secondary ones; explanations for them, based on anatomy and embryology, are put forward. The implications of the various anomalies are discussed and the ethical aspects of attempted separation in these major unions considered.", "contents": "Craniopagus twins: surgical anatomy and embryology and their implications. Craniopagus is of two types, partial and total. In the partial form the union is of limited extent, particularly as regards its depth, and separation can be expected to be followed by the survival of both children to lead normal lives. In the total form, of which three varieties can be recognized, the two brains can be regarded as lying within a single cranium and a series of gross intracranial abnormalities develops. These include deformity of the skull base, deformity and displacement of the cerebrum, and a gross circulatory abnormality. It is considered that these and other abnormalities, unlike the primary defect, which is defined, are secondary ones; explanations for them, based on anatomy and embryology, are put forward. The implications of the various anomalies are discussed and the ethical aspects of attempted separation in these major unions considered."} {"id": "PMID:1255208", "title": "Genetic associations between myasthenia gravis and the HL-A system.", "content": "HL-A antigens were determined in 159 myasthenic patients, 112 of whom were females and 47 males. Fifty-seven patients were thymectomized. The relationship between 23 different HL-A antigens and myasthenia gravis (MG) with reference to sex, age at onset, clinical course of MG, thymus histology, and auxiliary diseases of the patients, as well as the significance of these antigens to 245 relatives of myasthenics, were analysed. The frequencies of HL-A1 and HL-A8 were highly significantly higher in myasthenic patients than in normal Finnish controls. The increase of HL-A1 is secondary and due to a strong linkage disequilibrium between HL-A8 and HL-A1. HL-A8 appeared most often in females with onset of MG before the age of 35 years, and inpatients with thymus hyperplasia. No significant HL-A deviations were found in males or in females with later onset of disease. In seven thymoma patients the occurrence of W10 antigen was almost significantly increased.", "contents": "Genetic associations between myasthenia gravis and the HL-A system. HL-A antigens were determined in 159 myasthenic patients, 112 of whom were females and 47 males. Fifty-seven patients were thymectomized. The relationship between 23 different HL-A antigens and myasthenia gravis (MG) with reference to sex, age at onset, clinical course of MG, thymus histology, and auxiliary diseases of the patients, as well as the significance of these antigens to 245 relatives of myasthenics, were analysed. The frequencies of HL-A1 and HL-A8 were highly significantly higher in myasthenic patients than in normal Finnish controls. The increase of HL-A1 is secondary and due to a strong linkage disequilibrium between HL-A8 and HL-A1. HL-A8 appeared most often in females with onset of MG before the age of 35 years, and inpatients with thymus hyperplasia. No significant HL-A deviations were found in males or in females with later onset of disease. In seven thymoma patients the occurrence of W10 antigen was almost significantly increased."} {"id": "PMID:1255209", "title": "Serum immunogloblin levels in myasthenia gravis, polymyositis, and dermatomyositis.", "content": "Analyses of serum immunoglobulin (Ig) levels were performed in patients with myasthenia gravis, polymyositis and dermatomyositis, and in normal subjects. The mean IgG levels were elevated in the disease groups and there was minimal depression of serum IgM levels in nonthymectomized myasthenic patients. There was no consistent pattern with regard to selective immunoglobulin class abnormalities, effect of thymectomy in serial studies, and no evidence of gross humoral immunological deficiency as manifested by consistent depression of serum IgA, IgG, or IgM in the disease groups.", "contents": "Serum immunogloblin levels in myasthenia gravis, polymyositis, and dermatomyositis. Analyses of serum immunoglobulin (Ig) levels were performed in patients with myasthenia gravis, polymyositis and dermatomyositis, and in normal subjects. The mean IgG levels were elevated in the disease groups and there was minimal depression of serum IgM levels in nonthymectomized myasthenic patients. There was no consistent pattern with regard to selective immunoglobulin class abnormalities, effect of thymectomy in serial studies, and no evidence of gross humoral immunological deficiency as manifested by consistent depression of serum IgA, IgG, or IgM in the disease groups."} {"id": "PMID:1255210", "title": "Myasthenia gravis: clinical and histological features in relation to thymectomy.", "content": "The clinical and thymic histological features of 23 patients who underwent thymectomy for myasthenia gravis have been examined and compared. Eighty-two per cent of patients with a non-neoplastic gland containing numerous germinal centres improved postoperatively, whereas 83% of patients with a non-neoplastic gland containing no germinal centres deteriorated or died. Glands with only slight involution and containing numerous germinal centres were more commonly seen in young female patients. The evidence relating thymic histological appearances with the postoperative progress of patients with myasthenia gravis is reviewed.", "contents": "Myasthenia gravis: clinical and histological features in relation to thymectomy. The clinical and thymic histological features of 23 patients who underwent thymectomy for myasthenia gravis have been examined and compared. Eighty-two per cent of patients with a non-neoplastic gland containing numerous germinal centres improved postoperatively, whereas 83% of patients with a non-neoplastic gland containing no germinal centres deteriorated or died. Glands with only slight involution and containing numerous germinal centres were more commonly seen in young female patients. The evidence relating thymic histological appearances with the postoperative progress of patients with myasthenia gravis is reviewed."} {"id": "PMID:1255211", "title": "Transient eyelid retraction in myasthenia gravis.", "content": "Three patients with myasthenia gravis had transient retraction of the upper eyelids which usually followed prolonged upgaze and which persisted for many seconds. This could result from post-tetanic facilitation, myotonia, or a transient contracture. Retraction of this type is to be distinguished from both the long-standing unilateral retraction associated with ptosis of the contralateral eyelid and the fleeting lid twitch sign.", "contents": "Transient eyelid retraction in myasthenia gravis. Three patients with myasthenia gravis had transient retraction of the upper eyelids which usually followed prolonged upgaze and which persisted for many seconds. This could result from post-tetanic facilitation, myotonia, or a transient contracture. Retraction of this type is to be distinguished from both the long-standing unilateral retraction associated with ptosis of the contralateral eyelid and the fleeting lid twitch sign."} {"id": "PMID:1255212", "title": "Hypocalcaemic myopathy with paranoid psychosis.", "content": "A description is given of a patient with idiopathic hypoparathyroidism and a paranoid psychosis. Changes in muscle, electromyograms, and blood enzyme levels were related to hypocalcaemia. Reference is made to the elevations of these enzyme levels found in other cases of psychosis.", "contents": "Hypocalcaemic myopathy with paranoid psychosis. A description is given of a patient with idiopathic hypoparathyroidism and a paranoid psychosis. Changes in muscle, electromyograms, and blood enzyme levels were related to hypocalcaemia. Reference is made to the elevations of these enzyme levels found in other cases of psychosis."} {"id": "PMID:1255213", "title": "Ocular bobbing with survival.", "content": "A case is described of prolonged ocular bobbing with survival after subarachnoid haemorrhage from a pontine arteriovenous malformation. Hitherto, this sign has usually been associated with a rapidly fatal outcome.", "contents": "Ocular bobbing with survival. A case is described of prolonged ocular bobbing with survival after subarachnoid haemorrhage from a pontine arteriovenous malformation. Hitherto, this sign has usually been associated with a rapidly fatal outcome."} {"id": "PMID:1255214", "title": "Parallel variation of ventricular CSF tryptophan and free serum tryptophan in man.", "content": "Tryptophan was measured in the ventricular CSE and serum and the neutral amino acids leucine, isoleucine, valine, phenylalanine, and tyrosine were measured in the serum of two cases with ventricular drains. Samples were taken every two hours for 24 hours in one case and for 16 hours in the other. The CSF tryptophan was correlated significantly with the free--that is, non-albumin-bound--serum tryptophan but not with the total serum tryptophan. CSF tryptophan was not correlated significantly with the ratio of free serum tryptophan to the sum of the neutral amino acids. These data suggest that, in man, brain tryptophan concentrations are influenced by the free and not the total serum tryptophan and that physiological variations of the neutral amino acids do not appreciably influence the concentration of brain trytophan.", "contents": "Parallel variation of ventricular CSF tryptophan and free serum tryptophan in man. Tryptophan was measured in the ventricular CSE and serum and the neutral amino acids leucine, isoleucine, valine, phenylalanine, and tyrosine were measured in the serum of two cases with ventricular drains. Samples were taken every two hours for 24 hours in one case and for 16 hours in the other. The CSF tryptophan was correlated significantly with the free--that is, non-albumin-bound--serum tryptophan but not with the total serum tryptophan. CSF tryptophan was not correlated significantly with the ratio of free serum tryptophan to the sum of the neutral amino acids. These data suggest that, in man, brain tryptophan concentrations are influenced by the free and not the total serum tryptophan and that physiological variations of the neutral amino acids do not appreciably influence the concentration of brain trytophan."} {"id": "PMID:1255215", "title": "Gliomas (astrocytomas) of the brain-stem with spinal intra- and extradural metastases: report of three cases.", "content": "Astrocytomas of the pons and medulla oblongata ('brain-stem gliomas') while often invasive locally, do not as a rule seed and metastasize along the spinal meninges. Three cases are here reported (two adults, one child) in whom astrocytoma of the brain-stem metastasized along the spinal cord. The dura mater itself and the spinal epidural space were invaded in two cases. The child and one adult had a pontine astrocytoma, the other adult's tumour originated in the medulla oblongata. In the two cases that came to necropsy the tumour of the brain-stem was much better differentiated than the meningeal deposits. These three cases suggest that the possibility of spinal spread of brain-stem gliomas should be considered when dealing with diagnostic and therapeutic problems of such patients.", "contents": "Gliomas (astrocytomas) of the brain-stem with spinal intra- and extradural metastases: report of three cases. Astrocytomas of the pons and medulla oblongata ('brain-stem gliomas') while often invasive locally, do not as a rule seed and metastasize along the spinal meninges. Three cases are here reported (two adults, one child) in whom astrocytoma of the brain-stem metastasized along the spinal cord. The dura mater itself and the spinal epidural space were invaded in two cases. The child and one adult had a pontine astrocytoma, the other adult's tumour originated in the medulla oblongata. In the two cases that came to necropsy the tumour of the brain-stem was much better differentiated than the meningeal deposits. These three cases suggest that the possibility of spinal spread of brain-stem gliomas should be considered when dealing with diagnostic and therapeutic problems of such patients."} {"id": "PMID:1255216", "title": "Acute confusional states with right middle cerebral artery infarctions.", "content": "Three patients presenting predominantly with acute confusional states (ACS) are shown to have infarctions in the distribution of the right middle cerebral artery. It is suggested that the main deficit in ACS is in the function of selective attention. On the basis of cortical connections of homologous areas in the monkey brain, it is argued that this deficit arises from lesions in convergence areas for association cortex.", "contents": "Acute confusional states with right middle cerebral artery infarctions. Three patients presenting predominantly with acute confusional states (ACS) are shown to have infarctions in the distribution of the right middle cerebral artery. It is suggested that the main deficit in ACS is in the function of selective attention. On the basis of cortical connections of homologous areas in the monkey brain, it is argued that this deficit arises from lesions in convergence areas for association cortex."} {"id": "PMID:1255217", "title": "Jaw reflexes and masseter electromyograms in mesencephalic and pontine lesions: an electrodiagnostic study.", "content": "Jaw reflexes and masseter electromyograms were studied in five patients with mesencephalic and 11 patients with pontine lesions, vascular or tumorous in nature. In the former group jaw reflexes were abnormal, being delayed or absent, whereas masseter electromyograms were normal. In the latter group, both jaw reflexes and masseter EMG, showing denervation, were abnormal in six and both normal in five cases. It is suggested that the afferent limb of the human jaw reflex passes through the mesencephalic trigeminal nucleus. The methods proved to be valuable in the diagnosis of mesencephalic and pontine lesions involving the fifth cranial nerve.", "contents": "Jaw reflexes and masseter electromyograms in mesencephalic and pontine lesions: an electrodiagnostic study. Jaw reflexes and masseter electromyograms were studied in five patients with mesencephalic and 11 patients with pontine lesions, vascular or tumorous in nature. In the former group jaw reflexes were abnormal, being delayed or absent, whereas masseter electromyograms were normal. In the latter group, both jaw reflexes and masseter EMG, showing denervation, were abnormal in six and both normal in five cases. It is suggested that the afferent limb of the human jaw reflex passes through the mesencephalic trigeminal nucleus. The methods proved to be valuable in the diagnosis of mesencephalic and pontine lesions involving the fifth cranial nerve."} {"id": "PMID:1255218", "title": "Localized sympathetic overactivity: an uncommon complication of lung cancer.", "content": "Direct nerve infiltration by tumour tissue usually produces pain, and loss of motor, sensory, and autonomic function. Two patients are reported in whom a major symptom of nerve infiltration was sympathetic overactivity manifested by excessive spontaneous sweating.", "contents": "Localized sympathetic overactivity: an uncommon complication of lung cancer. Direct nerve infiltration by tumour tissue usually produces pain, and loss of motor, sensory, and autonomic function. Two patients are reported in whom a major symptom of nerve infiltration was sympathetic overactivity manifested by excessive spontaneous sweating."} {"id": "PMID:1255219", "title": "Pressure palsy of the ulnar nerve with prolonged conduction block.", "content": "A patient is described in whom conduction block occurred in the ulnar nerve after a pressure palsy and persisted for 16 weeks. The unusually long delay in recovery is discussed.", "contents": "Pressure palsy of the ulnar nerve with prolonged conduction block. A patient is described in whom conduction block occurred in the ulnar nerve after a pressure palsy and persisted for 16 weeks. The unusually long delay in recovery is discussed."} {"id": "PMID:1255220", "title": "Spatiotemporal organization of cat lateral geniculate receptive fields.", "content": "Spatial and temporal properties of LGN receptive fields were studied by flashing a small bar of light across the field in 28 discrete steps. The flashes at each of the spatial positions were used to produce 28 PST histograms. These histograms were in turn displayed as a plane, with space on the chi axis, time on the psi axis, and probability of firing on the zota axis. These response planes demonstrate that the terms on, off, center, and surround do not adequately describe when the simplest LGN receptive field. We, therefore, introduce a new terminology describing the four major spatiotemporal components of LGN fields. The primary excitatory (PE) domain corresponds to the strongest excitatory response, the secondary excitatory (SE) domain corresponds to the second-strongest excitatory domain, the primary inhibitory (PI) domain corresponds to the strongest inhibitory domain and, finally, the secondary inhibitory (SI) domain corresponds to the second-strongest inhibitory domain. Based on the arrangement of these four domains, it is possible to divide LGN fields into four major categories: 1) homogeneous-on, on-center receptive fields which have a spatially homogeneous distribution of domains; 2) homogeneous-off, off-center receptive fields which have a spatially homogeneous distribution of domains; 3) heterogeneous-on, on-center receptive fields which have a spatially heterogeneous distribution of domains; and 4) heterogeneous-off, off-center receptive fields which have a spatially heterogeneous distribution of domains; 3) heterogeneous-on, on-center receptive fields which have a spatially heterogeneous distribution of domains; and 4) heterogeneous-off, off-center receptive fields which have a spatially heterogeneous distribution of domains. Using grating, it can be demonstrated that our heterogeneous/homogeneous fields correspond to X/Y fields, respectively. These data lead us to suggest that retinal PE domains generage LGN PE and SI domains, while retinal SE domains generate LGN SE and SI domains.", "contents": "Spatiotemporal organization of cat lateral geniculate receptive fields. Spatial and temporal properties of LGN receptive fields were studied by flashing a small bar of light across the field in 28 discrete steps. The flashes at each of the spatial positions were used to produce 28 PST histograms. These histograms were in turn displayed as a plane, with space on the chi axis, time on the psi axis, and probability of firing on the zota axis. These response planes demonstrate that the terms on, off, center, and surround do not adequately describe when the simplest LGN receptive field. We, therefore, introduce a new terminology describing the four major spatiotemporal components of LGN fields. The primary excitatory (PE) domain corresponds to the strongest excitatory response, the secondary excitatory (SE) domain corresponds to the second-strongest excitatory domain, the primary inhibitory (PI) domain corresponds to the strongest inhibitory domain and, finally, the secondary inhibitory (SI) domain corresponds to the second-strongest inhibitory domain. Based on the arrangement of these four domains, it is possible to divide LGN fields into four major categories: 1) homogeneous-on, on-center receptive fields which have a spatially homogeneous distribution of domains; 2) homogeneous-off, off-center receptive fields which have a spatially homogeneous distribution of domains; 3) heterogeneous-on, on-center receptive fields which have a spatially heterogeneous distribution of domains; and 4) heterogeneous-off, off-center receptive fields which have a spatially heterogeneous distribution of domains; 3) heterogeneous-on, on-center receptive fields which have a spatially heterogeneous distribution of domains; and 4) heterogeneous-off, off-center receptive fields which have a spatially heterogeneous distribution of domains. Using grating, it can be demonstrated that our heterogeneous/homogeneous fields correspond to X/Y fields, respectively. These data lead us to suggest that retinal PE domains generage LGN PE and SI domains, while retinal SE domains generate LGN SE and SI domains."} {"id": "PMID:1255221", "title": "Interactions between cat lateral geniculate neurons.", "content": "Action potentials of 31 pairs of cat LGN neurons were recorded on single electrodes. Cross-correlograms, response planes, and a new function, the logical response plane, were calculated. The cross-correlograms between these pairs revealed four interactive classes: 1) a class with a flat cross-correlogram, 2) a class with a peak in the center of the cross-correlogram seen both during spontaneous activity and during driven activity, 3) a class with an inhibitory dip in the center of the cross-correlogram seen only when the cell pairs were driven by a stimulus and predicted by the shift predictor, 4) finally, a class with an inhibitory dip in the center of the cross-correlogram seen both during driven activity and spontaneous activity and not predicted by the shift predictor. Response plane pairs calculated for the unit pairs with flat cross-correlograms showed no predictable relationship. The pairs with a dip in the center of the cross-correlograms always had response planes that were antagonistic (i.e., approximate negative images of each other). When one cell was excited, the second cell was inhibited, and vice versa. More detailed analysis, using the logical response plane, demonstrated that the majority of the antagonistic response planes had either excitatory or inhibitory overlap. That is, the cells were simultaneously excited and/or inhibited at specific spatiotemporal loci on the response plane. These data are consistent with a feed-forward inhibitory circuit in LGN. Furthermore, the data suggest that retinal centers (PE domains) produce LGN excitatory centers (PE domains) and inhibitory centers (PI domains). In turn, retinal excitatory surrounds (SE domains) produce LGN excitatory surrounds (SE domains) and inhibitory surrounds (SI domains).", "contents": "Interactions between cat lateral geniculate neurons. Action potentials of 31 pairs of cat LGN neurons were recorded on single electrodes. Cross-correlograms, response planes, and a new function, the logical response plane, were calculated. The cross-correlograms between these pairs revealed four interactive classes: 1) a class with a flat cross-correlogram, 2) a class with a peak in the center of the cross-correlogram seen both during spontaneous activity and during driven activity, 3) a class with an inhibitory dip in the center of the cross-correlogram seen only when the cell pairs were driven by a stimulus and predicted by the shift predictor, 4) finally, a class with an inhibitory dip in the center of the cross-correlogram seen both during driven activity and spontaneous activity and not predicted by the shift predictor. Response plane pairs calculated for the unit pairs with flat cross-correlograms showed no predictable relationship. The pairs with a dip in the center of the cross-correlograms always had response planes that were antagonistic (i.e., approximate negative images of each other). When one cell was excited, the second cell was inhibited, and vice versa. More detailed analysis, using the logical response plane, demonstrated that the majority of the antagonistic response planes had either excitatory or inhibitory overlap. That is, the cells were simultaneously excited and/or inhibited at specific spatiotemporal loci on the response plane. These data are consistent with a feed-forward inhibitory circuit in LGN. Furthermore, the data suggest that retinal centers (PE domains) produce LGN excitatory centers (PE domains) and inhibitory centers (PI domains). In turn, retinal excitatory surrounds (SE domains) produce LGN excitatory surrounds (SE domains) and inhibitory surrounds (SI domains)."} {"id": "PMID:1255222", "title": "Responses of cats to sudden falls: an otolith-originating reflex assisting landing.", "content": "A short-latency electromyographic response has been demonstrated in the human gastrocnemius during unexpected falls (11). The hypothesis that it is a form of otolith-spinal reflex has been tested in the cat. Electromyographic activity was measured in four muscles while suddenly and unexpectedly dropping a series of six cats from 50 cm above the ground. In normal animals, electrical activation of all muscles tested occurred in two distinct phases. An early burst commenced as early as 15 ms from the instant of release, was usually spindle shaped, and often but not always disappeared by 100 ms. This burst was totally and permanently abolished by bilateral labyrinthectomy, but not by selective inactivation of the relevant semicircular canals. A later phase of muscle activity commenced 75-140 ms after release and gradually built up and then subsided, rougly centered about the movement of landing on the ground. This activity was not greatly altered by labyrinthectomy. The present results appear to confirm that the early electromyographic response to sudden falls is due to an otolith-spinal reflex. A later component is nonlabyrinthine in origin, however. Smooth landings from short falls are not possible in the absence of either phase of the response.", "contents": "Responses of cats to sudden falls: an otolith-originating reflex assisting landing. A short-latency electromyographic response has been demonstrated in the human gastrocnemius during unexpected falls (11). The hypothesis that it is a form of otolith-spinal reflex has been tested in the cat. Electromyographic activity was measured in four muscles while suddenly and unexpectedly dropping a series of six cats from 50 cm above the ground. In normal animals, electrical activation of all muscles tested occurred in two distinct phases. An early burst commenced as early as 15 ms from the instant of release, was usually spindle shaped, and often but not always disappeared by 100 ms. This burst was totally and permanently abolished by bilateral labyrinthectomy, but not by selective inactivation of the relevant semicircular canals. A later phase of muscle activity commenced 75-140 ms after release and gradually built up and then subsided, rougly centered about the movement of landing on the ground. This activity was not greatly altered by labyrinthectomy. The present results appear to confirm that the early electromyographic response to sudden falls is due to an otolith-spinal reflex. A later component is nonlabyrinthine in origin, however. Smooth landings from short falls are not possible in the absence of either phase of the response."} {"id": "PMID:1255223", "title": "Trial sequence of changed unit activity in auditory system of alert rat during conditioned response acquisition and extinction.", "content": "1. The activity of units in the auditory system of alert, freely moving rats was studies during the acquisition and extinction of a tone-signaled, appetitive classically conditioned response. Responses of neurons in inferior colliculus (N = 28), medial geniculate (N = 32), posterior nucleus of thalamus (N = 28), pretectal region (N = 19), and cortex (N = 100) were studies in 74 rats across 10-trial blocks. 2. During behavioral acquisition, neurons in posterior nucleus of thalamus were the first to show response increments to CS+ onset. They were followed by neurons in cortex, pretectal region, medial geniculate, inferior colliculus and by movement behavior. 3. Prestimulus background rates during acquisition showed significant decrements in cortical neurons. These background decrements began to be evidenced in the trial series before the response increases in posterior nucleus. These data strengthened the suggestion of a previous study that posterior nucleus responses could be dependent on tonic modulation from cortex. 4. Extinction appeared to be largely a reverse of acquisition. Cortex and behavior showed response decrements first in the trial series. They were followed by medial geniculate, pretectal region, posterior nucleus, and inferior colliculus neurons. 5. The hypothesis was advanced that the auditory lemniscal adjunct afferent system may play a primary role in the early phases of auditory conditioned-response acquisition.", "contents": "Trial sequence of changed unit activity in auditory system of alert rat during conditioned response acquisition and extinction. 1. The activity of units in the auditory system of alert, freely moving rats was studies during the acquisition and extinction of a tone-signaled, appetitive classically conditioned response. Responses of neurons in inferior colliculus (N = 28), medial geniculate (N = 32), posterior nucleus of thalamus (N = 28), pretectal region (N = 19), and cortex (N = 100) were studies in 74 rats across 10-trial blocks. 2. During behavioral acquisition, neurons in posterior nucleus of thalamus were the first to show response increments to CS+ onset. They were followed by neurons in cortex, pretectal region, medial geniculate, inferior colliculus and by movement behavior. 3. Prestimulus background rates during acquisition showed significant decrements in cortical neurons. These background decrements began to be evidenced in the trial series before the response increases in posterior nucleus. These data strengthened the suggestion of a previous study that posterior nucleus responses could be dependent on tonic modulation from cortex. 4. Extinction appeared to be largely a reverse of acquisition. Cortex and behavior showed response decrements first in the trial series. They were followed by medial geniculate, pretectal region, posterior nucleus, and inferior colliculus neurons. 5. The hypothesis was advanced that the auditory lemniscal adjunct afferent system may play a primary role in the early phases of auditory conditioned-response acquisition."} {"id": "PMID:1255224", "title": "Responses to tones and noise of single cells in dorsal cochlear nucleus of unanesthetized cats.", "content": "1. Single-unit responses in the dorsal cochlear nucleus of unanesthetized, decerebrate cats have been divided into two categoreis. These have been differentiated on the basis of responses to best-frequency tones. Type IV units responded to best-frequency tones with excitation from threshold to about 20 or 30 dB above threshold; at higher levels, their response was inhibitory. In a few cases, the excitatory area near threshold was not seen and in a few others, the response became excitatory again at high levels. Type IV units could be divided into two groups based on the length of time that inhibition was maintained in response to long tones. Type IV units are not seen in anesthetized cats. 2. Type II/III units responded to best-frequency tones of all levels with excitation. Nonmonotonic rate versus level functions were seen in type II/III units, but they were of much less drastic character; the discharge rate of nonmonotonic type II/III units was still well above spontaneous rate for tones 50 dB above threshold. Type II/III units defined in this way were found to have, on the average, lower rates of spontaneous activity and higher thresholds than type IV units. 3. Type II/III units responded weakly to broad-band noise in comparison to auditory nerve fibers and many of them did not respond at all to noise. Type IV units, with best frequencies above 0.9 kHz, gave excitatory responses to noise. 4. The inhibitory response areas of type IV units could be divided into two areas: a central inhibitory area in the vicinity of best frequency where on- and off-discharges and afterdischarges were seen; and inhibitory side bands at higher and lower frequencies where simple inhibitory responses were seen. In four units, it was possible to show that the central inhibitory area was converted to an excitatory area after administration of an anesthetic dose of pentobarbital. 5. Most type II/III and type IV units could be excited or inhibited by stimuli in the contralateral ear. Broad-band noise was a more effective contralateral stimulus than tones at the ipsilateral best frequency. 6. On the basis of the properties of type II/III and type IV cells, it is suggested that type II/III responses are recorded from interneurons which provide a large share of the inhibitory imput to type IV cells.", "contents": "Responses to tones and noise of single cells in dorsal cochlear nucleus of unanesthetized cats. 1. Single-unit responses in the dorsal cochlear nucleus of unanesthetized, decerebrate cats have been divided into two categoreis. These have been differentiated on the basis of responses to best-frequency tones. Type IV units responded to best-frequency tones with excitation from threshold to about 20 or 30 dB above threshold; at higher levels, their response was inhibitory. In a few cases, the excitatory area near threshold was not seen and in a few others, the response became excitatory again at high levels. Type IV units could be divided into two groups based on the length of time that inhibition was maintained in response to long tones. Type IV units are not seen in anesthetized cats. 2. Type II/III units responded to best-frequency tones of all levels with excitation. Nonmonotonic rate versus level functions were seen in type II/III units, but they were of much less drastic character; the discharge rate of nonmonotonic type II/III units was still well above spontaneous rate for tones 50 dB above threshold. Type II/III units defined in this way were found to have, on the average, lower rates of spontaneous activity and higher thresholds than type IV units. 3. Type II/III units responded weakly to broad-band noise in comparison to auditory nerve fibers and many of them did not respond at all to noise. Type IV units, with best frequencies above 0.9 kHz, gave excitatory responses to noise. 4. The inhibitory response areas of type IV units could be divided into two areas: a central inhibitory area in the vicinity of best frequency where on- and off-discharges and afterdischarges were seen; and inhibitory side bands at higher and lower frequencies where simple inhibitory responses were seen. In four units, it was possible to show that the central inhibitory area was converted to an excitatory area after administration of an anesthetic dose of pentobarbital. 5. Most type II/III and type IV units could be excited or inhibited by stimuli in the contralateral ear. Broad-band noise was a more effective contralateral stimulus than tones at the ipsilateral best frequency. 6. On the basis of the properties of type II/III and type IV cells, it is suggested that type II/III responses are recorded from interneurons which provide a large share of the inhibitory imput to type IV cells."} {"id": "PMID:1255225", "title": "Mossy fiber neck and second-order labyrinthine projections to cat flocculus.", "content": "In five decerebrate cats and in two under N2O-O2 anesthesia, a bipolar electrode array was inserted into a granular layer in the rostral flocculus. At this location MF field potentials were evoked by stimulation of the ipsilateral vestibular nerve and of the C2 dorsal root ganglion. Stimulation through the array was used to fire brain stem neurons antidromically. The activity of these neurons was recorded extracellularly with glass microelectrodes. Stimulation of the C2 dorsal root ganglion evoked in the caudal lateral brain stem a field potential caused by the arrival of impulses in primary afferent fibers. Cells projecting to the flocculus also responded to the stimulus, usually monosynaptically. These neurons were fired by stimulation of the area of the atlantoaxial joint. They did not respond to stimulation of the contralateral C2 dorsal root ganglion, and responded only rarely to stimulation of the dorsal rami of the C2 and C3 spinal nerves. Stimulation of the vestibular nerve was ineffective. Another group of cells projecting to the flocculus was fired at short latency by stimulation of the ipsilateral vestibular nerve. These neurons were usually inhibited by stimulation of the contralateral vestibular nerve. They were not affected by stimulation of any neck afferents. The location of many recording locations was identified by means of fast green dye marks. Most neurons relaying neck activity were in group x of Brodal and Pompeiano (4), a few were in the external cuneate nucleus, and one was in the descending vestibular nucleus. Neurons relaying labyrinthine activity were in the descending vestibular nucleus; one was found in the medial nucleus, in which tracks were made only rarely. There are two parallel pathways relaying neck and labyrinthine activity to the flocculus. While they are separate at the level of the brain stem, they converge in the same rostral areas of the flocculus. The neck afferent information may be required for proper performance of the flocculus in eye-movement control.", "contents": "Mossy fiber neck and second-order labyrinthine projections to cat flocculus. In five decerebrate cats and in two under N2O-O2 anesthesia, a bipolar electrode array was inserted into a granular layer in the rostral flocculus. At this location MF field potentials were evoked by stimulation of the ipsilateral vestibular nerve and of the C2 dorsal root ganglion. Stimulation through the array was used to fire brain stem neurons antidromically. The activity of these neurons was recorded extracellularly with glass microelectrodes. Stimulation of the C2 dorsal root ganglion evoked in the caudal lateral brain stem a field potential caused by the arrival of impulses in primary afferent fibers. Cells projecting to the flocculus also responded to the stimulus, usually monosynaptically. These neurons were fired by stimulation of the area of the atlantoaxial joint. They did not respond to stimulation of the contralateral C2 dorsal root ganglion, and responded only rarely to stimulation of the dorsal rami of the C2 and C3 spinal nerves. Stimulation of the vestibular nerve was ineffective. Another group of cells projecting to the flocculus was fired at short latency by stimulation of the ipsilateral vestibular nerve. These neurons were usually inhibited by stimulation of the contralateral vestibular nerve. They were not affected by stimulation of any neck afferents. The location of many recording locations was identified by means of fast green dye marks. Most neurons relaying neck activity were in group x of Brodal and Pompeiano (4), a few were in the external cuneate nucleus, and one was in the descending vestibular nucleus. Neurons relaying labyrinthine activity were in the descending vestibular nucleus; one was found in the medial nucleus, in which tracks were made only rarely. There are two parallel pathways relaying neck and labyrinthine activity to the flocculus. While they are separate at the level of the brain stem, they converge in the same rostral areas of the flocculus. The neck afferent information may be required for proper performance of the flocculus in eye-movement control."} {"id": "PMID:1255226", "title": "Reversal properties of climbing fiber potential in cat Purkinje cells: an example of a distributed synapse.", "content": "1. The electrophysiological properties of the EPSP generated in Purkinje cells by the activation of CFs were studies in the cat cerebellar cortex. 2. CF-EPSPs were evoked by electrical stimulation of the cerebellar white matter and recorded intracellularly from the soma of the Purkinje cells. 3. Current was injected into the Purkinje cells via the recording micropipette using a bridge amplifer in order to study the reversal properties of the EPSP. 4. The CF-EPSP reversal was biphasic with the early portion reversing first. 5. The reversed EPSP waveform was not a mirror image of the EPSP, but displayed a briefer time course. 6. A four-compartment computer stimulation showed that the reversal properities of the CF-EPSP were explicable in terms of a distributed synapse on a cable. 7. The biphasic reversal and asymmetry were shown to be due to the spatially nonuniform potential distribution created by the somatic current injection, which predominantly reversed the proximal part of the distributed synapse. Delayed rectification may also have contributed to the reversal asymmetry. 8. The advantages of a distributed synapse over a point synapse are discussed and the reversal properties of the CF-EPSP compared to those of the Ia-evoked EPSP in motoneurons.", "contents": "Reversal properties of climbing fiber potential in cat Purkinje cells: an example of a distributed synapse. 1. The electrophysiological properties of the EPSP generated in Purkinje cells by the activation of CFs were studies in the cat cerebellar cortex. 2. CF-EPSPs were evoked by electrical stimulation of the cerebellar white matter and recorded intracellularly from the soma of the Purkinje cells. 3. Current was injected into the Purkinje cells via the recording micropipette using a bridge amplifer in order to study the reversal properties of the EPSP. 4. The CF-EPSP reversal was biphasic with the early portion reversing first. 5. The reversed EPSP waveform was not a mirror image of the EPSP, but displayed a briefer time course. 6. A four-compartment computer stimulation showed that the reversal properities of the CF-EPSP were explicable in terms of a distributed synapse on a cable. 7. The biphasic reversal and asymmetry were shown to be due to the spatially nonuniform potential distribution created by the somatic current injection, which predominantly reversed the proximal part of the distributed synapse. Delayed rectification may also have contributed to the reversal asymmetry. 8. The advantages of a distributed synapse over a point synapse are discussed and the reversal properties of the CF-EPSP compared to those of the Ia-evoked EPSP in motoneurons."} {"id": "PMID:1255227", "title": "Long spinal and pyramidal actions on hindlimb motoneurons of the marsupial brush-tailed possum, Trichosurus vulpecula.", "content": "The existence of descending propriospinal reflex linkages between forelimbs and hindlimbs has been established in the brush-tailed possum (Trichosurus vulpecula). In animals under chloralose anesthesia and with intact brain stem, forelimb volleys evoked facilitation of flexor and extensor monosynaptic reflexes of both hindlimbs, more pronounced on the ipsilateral side. Powerful inhibition of briefer latency and restricted to ipsilateral flexor digitorum longus (FDL) motoneurons was also brought about by forelimb volleys; at latencies exceeding 20-30 ms, FDL inhibition was usually replaced by facilitation. Distinctness of the two long spinal actions was shown by differences in forelimb receptive fields and in threshold of the executant afferent fibers. The field for reflex inhibition was located distally in the forepaw region, that for facilitation being wider, including deep as well as superficial tissues. Threshold of afferent fibers evoking inhibition was lower than that for facilitation. The descending long spinal actions were compared with those set up by repetitive stimulation of the motor cortex contralateral to the test hindlimb reflexes. In agreement with previous work, strong facilitation of most flexor or extensor motoneurons was produced, including those of quadriceps and ankle flexors, as well as gastrocnemius and hamstring motor nuclei; inhibition consistently appeared only in the FDL motoneuron pool. Weak and inconstant inhibitory action was occasionally observed in other motor pools. Pyramidal tract section abolished the cortical inhibition of FDL, but had little effect on facilitation; both long spinal actions were unchanged. Pyramid-sparing brain stem section greatly reduced both cortical and long spinal facilitatory action, but had little or no effect on FDL inhibition from either source. Interaction experiments demonstrated facilitation of weak inhibitory actions on FDL motoneurons of forelimb and cortical stimulation when elicited together, suggesting a sharing by the two inputs of common interneuronal elements. The observation is consistent with the notion that the long propriospinal system responsible for FDL inhibition from the forepaw might provide the pathway for pyramidal inhibition of the same group of motoneurons.", "contents": "Long spinal and pyramidal actions on hindlimb motoneurons of the marsupial brush-tailed possum, Trichosurus vulpecula. The existence of descending propriospinal reflex linkages between forelimbs and hindlimbs has been established in the brush-tailed possum (Trichosurus vulpecula). In animals under chloralose anesthesia and with intact brain stem, forelimb volleys evoked facilitation of flexor and extensor monosynaptic reflexes of both hindlimbs, more pronounced on the ipsilateral side. Powerful inhibition of briefer latency and restricted to ipsilateral flexor digitorum longus (FDL) motoneurons was also brought about by forelimb volleys; at latencies exceeding 20-30 ms, FDL inhibition was usually replaced by facilitation. Distinctness of the two long spinal actions was shown by differences in forelimb receptive fields and in threshold of the executant afferent fibers. The field for reflex inhibition was located distally in the forepaw region, that for facilitation being wider, including deep as well as superficial tissues. Threshold of afferent fibers evoking inhibition was lower than that for facilitation. The descending long spinal actions were compared with those set up by repetitive stimulation of the motor cortex contralateral to the test hindlimb reflexes. In agreement with previous work, strong facilitation of most flexor or extensor motoneurons was produced, including those of quadriceps and ankle flexors, as well as gastrocnemius and hamstring motor nuclei; inhibition consistently appeared only in the FDL motoneuron pool. Weak and inconstant inhibitory action was occasionally observed in other motor pools. Pyramidal tract section abolished the cortical inhibition of FDL, but had little effect on facilitation; both long spinal actions were unchanged. Pyramid-sparing brain stem section greatly reduced both cortical and long spinal facilitatory action, but had little or no effect on FDL inhibition from either source. Interaction experiments demonstrated facilitation of weak inhibitory actions on FDL motoneurons of forelimb and cortical stimulation when elicited together, suggesting a sharing by the two inputs of common interneuronal elements. The observation is consistent with the notion that the long propriospinal system responsible for FDL inhibition from the forepaw might provide the pathway for pyramidal inhibition of the same group of motoneurons."} {"id": "PMID:1255228", "title": "Intracellular responses from granule cell layer in slices of rat hippocampus: perforant path synapse.", "content": "Intracellular responses were recorded in vitro from the denate granule cell layer of hippocampal slices prepared from adult rats. Spontaneous activity of granule cells in vitro consisted of action potentials and small, graded depolarizations, presumably of synaptic origin. Granule cells could be activated by injection of depolarizing current or release of hyperpolarizing current. Individual granule cells spatially summed input from the perforant path and fired multiple action potentials in vitro following strong presynaptic volleys. Depolarization decreased and hyperpolarization increased the EPSP amplitude, which is consistent with a conductance-increase mechanism. Although we could demonstrate postexcitatory inhibition in some cells, granule cells in vitro appeared to receive less inhibitory feedback than in vivo, EPSP amplitude and spike output of granule cells showed frequency potentiation and posttetanic potentiation to perforant path stimulation. These intracellular responses in vitro complement some of the findings from field-potential analyses of the dentate gyrus in intact animals.", "contents": "Intracellular responses from granule cell layer in slices of rat hippocampus: perforant path synapse. Intracellular responses were recorded in vitro from the denate granule cell layer of hippocampal slices prepared from adult rats. Spontaneous activity of granule cells in vitro consisted of action potentials and small, graded depolarizations, presumably of synaptic origin. Granule cells could be activated by injection of depolarizing current or release of hyperpolarizing current. Individual granule cells spatially summed input from the perforant path and fired multiple action potentials in vitro following strong presynaptic volleys. Depolarization decreased and hyperpolarization increased the EPSP amplitude, which is consistent with a conductance-increase mechanism. Although we could demonstrate postexcitatory inhibition in some cells, granule cells in vitro appeared to receive less inhibitory feedback than in vivo, EPSP amplitude and spike output of granule cells showed frequency potentiation and posttetanic potentiation to perforant path stimulation. These intracellular responses in vitro complement some of the findings from field-potential analyses of the dentate gyrus in intact animals."} {"id": "PMID:1255229", "title": "Role of centrifugal pathways to cochlear nucleus in determination of critical bandwidth.", "content": "Atropine sulfate was applied locally to the cochlear nucleus of three unanesthetized cats in order to block the cholinergic centrifugal innervation of the nucleus. The critical bandwidth was measured behaviorally from the masked thresholds of 1-kHz tone pips in different bandwidths of masking noise. Atropine increased the critical bandwidth markedly. This suggests that normally the centrifugal pathways influence the critical bandwidth. Saline solutions alone had no effect, and if the cannula was not accurately implanted over the cochlear nucleus, atropine had no effect either.", "contents": "Role of centrifugal pathways to cochlear nucleus in determination of critical bandwidth. Atropine sulfate was applied locally to the cochlear nucleus of three unanesthetized cats in order to block the cholinergic centrifugal innervation of the nucleus. The critical bandwidth was measured behaviorally from the masked thresholds of 1-kHz tone pips in different bandwidths of masking noise. Atropine increased the critical bandwidth markedly. This suggests that normally the centrifugal pathways influence the critical bandwidth. Saline solutions alone had no effect, and if the cannula was not accurately implanted over the cochlear nucleus, atropine had no effect either."} {"id": "PMID:1255230", "title": "Relationship between visual and tactile representations in cat superior colliculus.", "content": "A stratified organization of visual, somatic and acoustic representations was observed in the cat SC. Cells of the superficial laminae were exclusively visual. Visual, somatic, and acoustic cells were observed in the intermediate laminae while the deeper laminae were predominantly nonvisual. A detailed examination of the tactile representation revealed a somatotopic plan which was in register with the overlying visuotopy. The magnified representation of central visual fields overlapped the magnified tactile representation of the face and, as visual RFS moved temporally, the underlying tactile RFS were displaced caudal and distal. This topographical overlap can be recognized if the visual field is depicted as a flexible sheet which is stretched over the body with the area centralis superimposed on the nose and the limbs radiating out at an acute angle. The overlapping topographies and similarities in stimulus specificity of somatic and visual cells, as well as the similar behavioral deficits previously described following SC lesions, suggests a functional parallel between modalities in the SC. The possibility that visual, somatic, and acoustic cells converge on a common delivery or distribution system, which is located in the intermediate-deeper SC strata and organizes orienting and following responses on the basis of multimodality cues, is discussed.", "contents": "Relationship between visual and tactile representations in cat superior colliculus. A stratified organization of visual, somatic and acoustic representations was observed in the cat SC. Cells of the superficial laminae were exclusively visual. Visual, somatic, and acoustic cells were observed in the intermediate laminae while the deeper laminae were predominantly nonvisual. A detailed examination of the tactile representation revealed a somatotopic plan which was in register with the overlying visuotopy. The magnified representation of central visual fields overlapped the magnified tactile representation of the face and, as visual RFS moved temporally, the underlying tactile RFS were displaced caudal and distal. This topographical overlap can be recognized if the visual field is depicted as a flexible sheet which is stretched over the body with the area centralis superimposed on the nose and the limbs radiating out at an acute angle. The overlapping topographies and similarities in stimulus specificity of somatic and visual cells, as well as the similar behavioral deficits previously described following SC lesions, suggests a functional parallel between modalities in the SC. The possibility that visual, somatic, and acoustic cells converge on a common delivery or distribution system, which is located in the intermediate-deeper SC strata and organizes orienting and following responses on the basis of multimodality cues, is discussed."} {"id": "PMID:1255231", "title": "Fast and slow pyramidal tract neurons: an intracellular analysis of their contrasting repetitive firing properties in the cat.", "content": "1. Intracellular recordings were made from an estimated 500 neurons in the sensorimotor cortex of barbiturate-anesthetized cats. Of those which were antidromically identified from the medullary pyramids, 70 were selected which also exhibited steady repetitive firing to steps of current injected through the recording electrode; 81% were \"fast\" (conduction velocity greater than 20 m/s) and 19% were \"slow\". 2. As shown by earlier workers, the spike duration is a function of conduction velocity; a spike duration of 1.0 ms is the dividing line between fast and slow. 3. Of the 57 fast pyramidal tract neurons (PTNS), 14 exhibited double spikes during otherwise rhythmic firing patterns to a step of injected current. These very short interspike intervals (usually 1.5-2.5 ms) were first seen interspersed in a rhythmic discharge (e.g., 50-ms intervals) but, with further increases in current strength, would come to dominate the firing pattern; e.g., double spikes every 40 ms. Further increases in current would typically shorten only the long intervals; e.g., 40-30 ms, but some fast PTNS developed triple spikes, etc. 4. The extra spike appears to arise from a large hump which follows most spikes in fast PTNS; while this humplike \"depolarising after-potential\" can also be seen in slow PTNS, it is small. Extra spikes were seen only in fast PTNS with large postspike humps; in perhaps half of the fast PTNS, extra spikes probably contributed to \"adaptation.\" 5. Slow PTNS often had frequency-current curves which were not repeatable; a \"hysteresis\" phenomenon could often be seen, where the proportionality constant relating current to firing rate decreased following high firing rates. 6. The B spike was distinguishable from the A spike in differentiated antidromic spikes in 77% of the slow PTNS, in only 14% of the fast PTNS which later exhibited double spikes during current-induced repetitive firing, and in 53% of the other fast PTNS. 7. The antidromic spike heights of doublet PTNS were not significantly different from those of other repetitively firing PTNS.", "contents": "Fast and slow pyramidal tract neurons: an intracellular analysis of their contrasting repetitive firing properties in the cat. 1. Intracellular recordings were made from an estimated 500 neurons in the sensorimotor cortex of barbiturate-anesthetized cats. Of those which were antidromically identified from the medullary pyramids, 70 were selected which also exhibited steady repetitive firing to steps of current injected through the recording electrode; 81% were \"fast\" (conduction velocity greater than 20 m/s) and 19% were \"slow\". 2. As shown by earlier workers, the spike duration is a function of conduction velocity; a spike duration of 1.0 ms is the dividing line between fast and slow. 3. Of the 57 fast pyramidal tract neurons (PTNS), 14 exhibited double spikes during otherwise rhythmic firing patterns to a step of injected current. These very short interspike intervals (usually 1.5-2.5 ms) were first seen interspersed in a rhythmic discharge (e.g., 50-ms intervals) but, with further increases in current strength, would come to dominate the firing pattern; e.g., double spikes every 40 ms. Further increases in current would typically shorten only the long intervals; e.g., 40-30 ms, but some fast PTNS developed triple spikes, etc. 4. The extra spike appears to arise from a large hump which follows most spikes in fast PTNS; while this humplike \"depolarising after-potential\" can also be seen in slow PTNS, it is small. Extra spikes were seen only in fast PTNS with large postspike humps; in perhaps half of the fast PTNS, extra spikes probably contributed to \"adaptation.\" 5. Slow PTNS often had frequency-current curves which were not repeatable; a \"hysteresis\" phenomenon could often be seen, where the proportionality constant relating current to firing rate decreased following high firing rates. 6. The B spike was distinguishable from the A spike in differentiated antidromic spikes in 77% of the slow PTNS, in only 14% of the fast PTNS which later exhibited double spikes during current-induced repetitive firing, and in 53% of the other fast PTNS. 7. The antidromic spike heights of doublet PTNS were not significantly different from those of other repetitively firing PTNS."} {"id": "PMID:1255232", "title": "Nonketotic hyperglycemic hyperosmolar coma. Report of neurosurgical cases with a review of mechanisms and treatment.", "content": "Seventy-eight critically ill patients who died while on the neurosurgical service were studied retrospectively to establish the prevalence of nonketotic hyperglycemic hyperosmolar coma (NHHC). All the patients had been comatose before death, and all underwent necropsy. Criteria for the diagnosis of NHHC included moderate-to-severe hyperglycemia with glucosuria, absence of significant acetonuria, hyperosmolarity with dehydration, and neurological dysfunction. This study revealed seven cases of unequivocal NHHC (9%), and six of hyperosmolarity but with incomplete records. Five of the seven confirmed cases of NHHC demonstrated no evidence of cerebral edema transtentorial herniation, or brain-stem damage, and showed central nervous system (CNS) lesions compatible with survival. Fatal complications of this syndrome, such as acute renal failure, terminal arrhythmias, and vascular accidents, both cerebral and systemic, were common in this series. The mechanism of coma in NHHC is believed related to shifts of free water from the cerebral extravascular space to the hypertonic intravascular space, with subsequent intracellular dehydration, accumulation of metabolic products of glucose, and brain shrinkage. It is uncertain whether injury to specific areas in the CNS is a predisposing factor to the development of NHHC. Factors documented to be significant in its development include nonspecific stress to primary illnesses, hyperosmolar tube feedings, dehydration, diabetes and mannitol, Dilantin, or steroid administration.", "contents": "Nonketotic hyperglycemic hyperosmolar coma. Report of neurosurgical cases with a review of mechanisms and treatment. Seventy-eight critically ill patients who died while on the neurosurgical service were studied retrospectively to establish the prevalence of nonketotic hyperglycemic hyperosmolar coma (NHHC). All the patients had been comatose before death, and all underwent necropsy. Criteria for the diagnosis of NHHC included moderate-to-severe hyperglycemia with glucosuria, absence of significant acetonuria, hyperosmolarity with dehydration, and neurological dysfunction. This study revealed seven cases of unequivocal NHHC (9%), and six of hyperosmolarity but with incomplete records. Five of the seven confirmed cases of NHHC demonstrated no evidence of cerebral edema transtentorial herniation, or brain-stem damage, and showed central nervous system (CNS) lesions compatible with survival. Fatal complications of this syndrome, such as acute renal failure, terminal arrhythmias, and vascular accidents, both cerebral and systemic, were common in this series. The mechanism of coma in NHHC is believed related to shifts of free water from the cerebral extravascular space to the hypertonic intravascular space, with subsequent intracellular dehydration, accumulation of metabolic products of glucose, and brain shrinkage. It is uncertain whether injury to specific areas in the CNS is a predisposing factor to the development of NHHC. Factors documented to be significant in its development include nonspecific stress to primary illnesses, hyperosmolar tube feedings, dehydration, diabetes and mannitol, Dilantin, or steroid administration."} {"id": "PMID:1255233", "title": "Possible mechanisms for observed pathophysiological variability in experimental spinal cord injury by the method of Allen.", "content": "Experimental spinal cord injuries were induced in dogs by dropping calibrated weights through a vented tube onto a small impounder resting on the surgically exposed cord. The motion of the impounder and the drop-mass were recorded by high-speed photography and the resulting data were compared to those obtained from a computer simulation of the dynamics of the injury mechanism. It is concluded that this method of induced spinal cord injuries may yield markedly different degrees of cord compression depending upon the parameters of the animal material and apparatus even when the gm-cm of impact energy is maintained at a constant value. Some approaches to standardization of this injury model are suggested.", "contents": "Possible mechanisms for observed pathophysiological variability in experimental spinal cord injury by the method of Allen. Experimental spinal cord injuries were induced in dogs by dropping calibrated weights through a vented tube onto a small impounder resting on the surgically exposed cord. The motion of the impounder and the drop-mass were recorded by high-speed photography and the resulting data were compared to those obtained from a computer simulation of the dynamics of the injury mechanism. It is concluded that this method of induced spinal cord injuries may yield markedly different degrees of cord compression depending upon the parameters of the animal material and apparatus even when the gm-cm of impact energy is maintained at a constant value. Some approaches to standardization of this injury model are suggested."} {"id": "PMID:1255234", "title": "Classification of cervical spondylosis or disc protrusion by preoperative evoked spinal electrogram. Follow-up study.", "content": "The evoked spinal electrogram (SEG) was studied in 11 patients with cervical spondylotic myelopathy or disc protrusion. All the patients were severely handicapped before surgery. The evoked SEG was classified in three grades before and during surgery. Periodic follow-up studies were done at 18 to 35 months, with an average of 24 months. Four of six patients were normal or slightly abnormal SEG recordings showed satisfactory improvement of the disability; however, only one patient showed any improvement when the recording was moderately or severely abnormal. Location of the cord lesion and type of surgery were similar in all patients examined, and the difference was likely ascribed to the physiological change of the intramedullary structures. The evoked SEG provides some information relative to the surgical treatment of spondylotic myelopathy or disc protrusion with cord lesion.", "contents": "Classification of cervical spondylosis or disc protrusion by preoperative evoked spinal electrogram. Follow-up study. The evoked spinal electrogram (SEG) was studied in 11 patients with cervical spondylotic myelopathy or disc protrusion. All the patients were severely handicapped before surgery. The evoked SEG was classified in three grades before and during surgery. Periodic follow-up studies were done at 18 to 35 months, with an average of 24 months. Four of six patients were normal or slightly abnormal SEG recordings showed satisfactory improvement of the disability; however, only one patient showed any improvement when the recording was moderately or severely abnormal. Location of the cord lesion and type of surgery were similar in all patients examined, and the difference was likely ascribed to the physiological change of the intramedullary structures. The evoked SEG provides some information relative to the surgical treatment of spondylotic myelopathy or disc protrusion with cord lesion."} {"id": "PMID:1255235", "title": "Chronic measurement of epidural pressure with an induction-powered oscillator transducer.", "content": "An induction-powered oscillator transducer (IPOT) was designed for the chronic measurement of epidural pressure. The transducer was completely implantable so all pressure measurements were made through the intact skin. The IPOT had a linear pressure range from -50 to +200 cm H2O, was sensitive to 1 mm H2O and had a zero drift of less than 1 mm H2O/day under full load. Zero drift was minimized by using a hermetically-sealed metal bellows transducing element which was chemically treated to prevent corrosion and creep. The correlation between epidural pressure and intraventricular pressure was determined during the first 24 hours after implantation in six dogs. Epidural pressure was found to be a linear function of intraventricular fluid pressure. Epidural pressure and intraventricular pressure were essential equal provided the epidural wedge pressure was minimized by proper insertion of the transducer. The correlation between epidural pressure and intraventricular pressure was determined after chronic implantation in five dogs. Epidural pressure was a linear function of intraventricular pressure in the chronically implanted dogs, but epidural pressure was not equal to intraventricular pressure. After chronic implantation, the epidural pressure transducer was not responsive to changes in intraventricular pressure because of mechanical changes in the dura. The dura became stiff and non-compliant. Maximum correlation between epidural pressure and intraventricular fluid pressure in chronic implantations will depend on judicious material selection and mechanical design at the transducer-dura interface.", "contents": "Chronic measurement of epidural pressure with an induction-powered oscillator transducer. An induction-powered oscillator transducer (IPOT) was designed for the chronic measurement of epidural pressure. The transducer was completely implantable so all pressure measurements were made through the intact skin. The IPOT had a linear pressure range from -50 to +200 cm H2O, was sensitive to 1 mm H2O and had a zero drift of less than 1 mm H2O/day under full load. Zero drift was minimized by using a hermetically-sealed metal bellows transducing element which was chemically treated to prevent corrosion and creep. The correlation between epidural pressure and intraventricular pressure was determined during the first 24 hours after implantation in six dogs. Epidural pressure was found to be a linear function of intraventricular fluid pressure. Epidural pressure and intraventricular pressure were essential equal provided the epidural wedge pressure was minimized by proper insertion of the transducer. The correlation between epidural pressure and intraventricular pressure was determined after chronic implantation in five dogs. Epidural pressure was a linear function of intraventricular pressure in the chronically implanted dogs, but epidural pressure was not equal to intraventricular pressure. After chronic implantation, the epidural pressure transducer was not responsive to changes in intraventricular pressure because of mechanical changes in the dura. The dura became stiff and non-compliant. Maximum correlation between epidural pressure and intraventricular fluid pressure in chronic implantations will depend on judicious material selection and mechanical design at the transducer-dura interface."} {"id": "PMID:1255236", "title": "Use of epsilon aminocaproic acid (EACA) in the preoperative management of ruptured intracranial aneurysms.", "content": "The authors report their experience with the use of epsilon aminocaproic acid (EACA) in the preoperative management of a series of patients with ruptured intracranial aneurysms. A similar series of patients was taken as control. They found that EACA is of definite value in preventing recurrent hemorrhage in the preoperative period. The significance of antifibrinolytic therapy in ruptured intracranial aneurysms is discussed.", "contents": "Use of epsilon aminocaproic acid (EACA) in the preoperative management of ruptured intracranial aneurysms. The authors report their experience with the use of epsilon aminocaproic acid (EACA) in the preoperative management of a series of patients with ruptured intracranial aneurysms. A similar series of patients was taken as control. They found that EACA is of definite value in preventing recurrent hemorrhage in the preoperative period. The significance of antifibrinolytic therapy in ruptured intracranial aneurysms is discussed."} {"id": "PMID:1255237", "title": "Glioma of the jugular foramen. Case report.", "content": "A case is presented of a jugular foramen syndrome caused by an ectopic glioma. Treatment was by intracapsular removal through a suboccipital craniectomy.", "contents": "Glioma of the jugular foramen. Case report. A case is presented of a jugular foramen syndrome caused by an ectopic glioma. Treatment was by intracapsular removal through a suboccipital craniectomy."} {"id": "PMID:1255238", "title": "Radionuclide cisternographic evaluation and follow-up of posttraumatic subconjunctival CSF loculation. Case report.", "content": "The case of a patient with massive, posttraumatic, subconjunctival cerebrospinal fluid collections is described in which diagnosis and postoperative management was simplified by serial radionuclide cisternography.", "contents": "Radionuclide cisternographic evaluation and follow-up of posttraumatic subconjunctival CSF loculation. Case report. The case of a patient with massive, posttraumatic, subconjunctival cerebrospinal fluid collections is described in which diagnosis and postoperative management was simplified by serial radionuclide cisternography."} {"id": "PMID:1255239", "title": "Chondrosarcoma of the cervical spine. Case report.", "content": "The authors present a case of chondrosarcoma involving the lateral mass of the C-2 vertebra, treated by an apparent total removal of the tumor. A review of the literature revealed that these patients can be cured in a significant number of cases if a radical removal is accomplished.", "contents": "Chondrosarcoma of the cervical spine. Case report. The authors present a case of chondrosarcoma involving the lateral mass of the C-2 vertebra, treated by an apparent total removal of the tumor. A review of the literature revealed that these patients can be cured in a significant number of cases if a radical removal is accomplished."} {"id": "PMID:1255240", "title": "Complication of a large cranial defect. Case report.", "content": "A patient with acute subdural hematoma was successfully treated with hemicraniectomy. He developed contralateral weakness 4 months after surgery which was reversed by cranioplasty. The presumptive mechanism is a gradient between atmospheric and intracranial pressure. Early cranioplasty is suggested to prevent this phenomenon.", "contents": "Complication of a large cranial defect. Case report. A patient with acute subdural hematoma was successfully treated with hemicraniectomy. He developed contralateral weakness 4 months after surgery which was reversed by cranioplasty. The presumptive mechanism is a gradient between atmospheric and intracranial pressure. Early cranioplasty is suggested to prevent this phenomenon."} {"id": "PMID:1255241", "title": "Cerebral arterial dolichoectasia with seizure. Case report.", "content": "Cerebral angiography, performed after a seizure in a patient with a life-long history of typical hemiplegic migraine, disclosed markedly dolichoectatic anterior and middle cerebral arteries. No abnormality of the adjacent capillary or venous structures was present. A positive brain scan was attributed to ischemia induced by vasospasm rather than to the corresponding large tortuous anterior and middle cerebral arteries. There were no permanent sequelae and the patient has been free of seizures on Dilantin and phenobarbital over a 3-year follow-up period. Angiographic demonstration or description of a similar ectatic set of anterior and middle cerebral arteries could not be found in the literature. The concurrence of seizures and hemiplegic migraine adds to the peculiarity of this case.", "contents": "Cerebral arterial dolichoectasia with seizure. Case report. Cerebral angiography, performed after a seizure in a patient with a life-long history of typical hemiplegic migraine, disclosed markedly dolichoectatic anterior and middle cerebral arteries. No abnormality of the adjacent capillary or venous structures was present. A positive brain scan was attributed to ischemia induced by vasospasm rather than to the corresponding large tortuous anterior and middle cerebral arteries. There were no permanent sequelae and the patient has been free of seizures on Dilantin and phenobarbital over a 3-year follow-up period. Angiographic demonstration or description of a similar ectatic set of anterior and middle cerebral arteries could not be found in the literature. The concurrence of seizures and hemiplegic migraine adds to the peculiarity of this case."} {"id": "PMID:1255242", "title": "Fatal paradoxical muscle embolization in traumatic carotid-cavernous fistula repair. Case report.", "content": "A unique case of fatal paradoxical muscle embolism in a patient with a traumatic carotid-cavernous fistula is described. The muscle plug intended to occlude a left-sided fistula passed through the large fistula, bypassed the lungs by way of a patent foramen ovale, and embolized through the right carotid artery to lodge the internal carotid and middle cerebral arteries producing fatal brain infarction.", "contents": "Fatal paradoxical muscle embolization in traumatic carotid-cavernous fistula repair. Case report. A unique case of fatal paradoxical muscle embolism in a patient with a traumatic carotid-cavernous fistula is described. The muscle plug intended to occlude a left-sided fistula passed through the large fistula, bypassed the lungs by way of a patent foramen ovale, and embolized through the right carotid artery to lodge the internal carotid and middle cerebral arteries producing fatal brain infarction."} {"id": "PMID:1255243", "title": "Middle cerebral artery embolectomy. Case report.", "content": "A patient who developed an embolic occlusion of the right middle cerebral artery while undergoing a cerebral arteriogram was successfully operated on by removal of the embolus under the surgical microscope. Early postoperative cerebrovascular spasm was a factor in the transient deterioration of the patient's neurological condition. When the patient was last seen 2 1/2 months after surgery she was almost intact neurologically with only a mild right parietal dysfunction but with total resolution of the left hemiplegia. The literature is reviewed.", "contents": "Middle cerebral artery embolectomy. Case report. A patient who developed an embolic occlusion of the right middle cerebral artery while undergoing a cerebral arteriogram was successfully operated on by removal of the embolus under the surgical microscope. Early postoperative cerebrovascular spasm was a factor in the transient deterioration of the patient's neurological condition. When the patient was last seen 2 1/2 months after surgery she was almost intact neurologically with only a mild right parietal dysfunction but with total resolution of the left hemiplegia. The literature is reviewed."} {"id": "PMID:1255245", "title": "Microvascular bipolar coagulator. Technical note.", "content": "A bipolar coagulator fabricated from jeweler's forceps of various sizes is described. The unit has proved very useful in microvascular neurosurgical procedures that require high magnification.", "contents": "Microvascular bipolar coagulator. Technical note. A bipolar coagulator fabricated from jeweler's forceps of various sizes is described. The unit has proved very useful in microvascular neurosurgical procedures that require high magnification."} {"id": "PMID:1255248", "title": "Cesium-129 myocardial scintigraphy to quantify myocardial infarction in dogs.", "content": "The sizes of surgically induced acute myocardial infarctions were quantified in a study of 28 dogs. Four projections (right and left anterior oblique, anterior, and left lateral) were obtained with 129Cs myocardial scintigraphy. Control images, taken before surgery, were compared with images taken 24-72 hr after coronary artery ligation. From postmortem examination the size of the infarct was determined and expressed as a percentage of the total left ventricle. On a standard diagram four independent observers marked the infarcted areas in each projection, expressed the severity of involvement in each area, and determined overall infarction size as a percentage of the total left ventricle. A nonlinear least-squares method was also employed to derive the size of the infarct, using the results from each observer's diagram. There were positive correlations between each observer's percentage estimate and the autopsy results. The overall accuracy of the least-squares method was similar to that of the individual observers. In this study, Observer 3 proved that acute myocardial infarcts can be quantified accurately from multiple scintigraphic projections of the myocardium, but the other three observers had difficulty in estimating infarct size. This difficulty probably resulted from the lack of well-validated criteria to aid the observer in determining the area of infarction, the severity of involvement within that area, or the total size of a myocardial infarct. Improvement in these estimates will require the development of definitive criteria, the use of optical scanners or computer processing, and combinations of radionuclides.", "contents": "Cesium-129 myocardial scintigraphy to quantify myocardial infarction in dogs. The sizes of surgically induced acute myocardial infarctions were quantified in a study of 28 dogs. Four projections (right and left anterior oblique, anterior, and left lateral) were obtained with 129Cs myocardial scintigraphy. Control images, taken before surgery, were compared with images taken 24-72 hr after coronary artery ligation. From postmortem examination the size of the infarct was determined and expressed as a percentage of the total left ventricle. On a standard diagram four independent observers marked the infarcted areas in each projection, expressed the severity of involvement in each area, and determined overall infarction size as a percentage of the total left ventricle. A nonlinear least-squares method was also employed to derive the size of the infarct, using the results from each observer's diagram. There were positive correlations between each observer's percentage estimate and the autopsy results. The overall accuracy of the least-squares method was similar to that of the individual observers. In this study, Observer 3 proved that acute myocardial infarcts can be quantified accurately from multiple scintigraphic projections of the myocardium, but the other three observers had difficulty in estimating infarct size. This difficulty probably resulted from the lack of well-validated criteria to aid the observer in determining the area of infarction, the severity of involvement within that area, or the total size of a myocardial infarct. Improvement in these estimates will require the development of definitive criteria, the use of optical scanners or computer processing, and combinations of radionuclides."} {"id": "PMID:1255249", "title": "Lymphangitic carcinomatosis: lung scan abnormalities.", "content": "Lymphangitic carcinomatosis of the lung is a late and fatal manifestation of cancer. The diagnosis is seldom made ante mortem. Four patients with breast cancer had autopsy-proven lymphangitic metastases of the lung. Of these patients, two had normal chest x-rays and three had normal ventilation lung scans. The perfusion lung scans of all four showed irregular peripheral perfusion defects. Autopsies showed permeation of the lymphatics by tumor and tumor emboli in small arteries and arterioles.", "contents": "Lymphangitic carcinomatosis: lung scan abnormalities. Lymphangitic carcinomatosis of the lung is a late and fatal manifestation of cancer. The diagnosis is seldom made ante mortem. Four patients with breast cancer had autopsy-proven lymphangitic metastases of the lung. Of these patients, two had normal chest x-rays and three had normal ventilation lung scans. The perfusion lung scans of all four showed irregular peripheral perfusion defects. Autopsies showed permeation of the lymphatics by tumor and tumor emboli in small arteries and arterioles."} {"id": "PMID:1255250", "title": "Comparison of 99mTc and 123I for thyroid imaging.", "content": "Thyroid images were obtained with 99mTc and 123I, using a scintillation camera and pinhole collimator, from 85 patients selected from over 1,000 patients predisposed to the development of thyroid neoplasms by prior radiotherapy. In 66 of 85 patients 99mTc and 123I gave essentially similar information, whereas in 19 patients some thyroid-image disparity was seen. In 11 of these 19, focal areas of increased 99mTc concentration were not seen with 123I. Radioiodide images showed slightly better contrast than the 99mTc images but required a longer imaging time and usually did not provide more information; in a few cases 99mTc showed abnormalities more readily. Regardless of which radionuclide was used, oblique views were needed to define some abnormalities. Currently 123I does not provide significant advantages over 99mTc for routine thyroid imaging. However, 123I is preferred in patients with very poor thyroid function and in those with suspected retrosternal thyroid tissue. In addition, areas of increased 99mTc concentration should also be studied with 123I.", "contents": "Comparison of 99mTc and 123I for thyroid imaging. Thyroid images were obtained with 99mTc and 123I, using a scintillation camera and pinhole collimator, from 85 patients selected from over 1,000 patients predisposed to the development of thyroid neoplasms by prior radiotherapy. In 66 of 85 patients 99mTc and 123I gave essentially similar information, whereas in 19 patients some thyroid-image disparity was seen. In 11 of these 19, focal areas of increased 99mTc concentration were not seen with 123I. Radioiodide images showed slightly better contrast than the 99mTc images but required a longer imaging time and usually did not provide more information; in a few cases 99mTc showed abnormalities more readily. Regardless of which radionuclide was used, oblique views were needed to define some abnormalities. Currently 123I does not provide significant advantages over 99mTc for routine thyroid imaging. However, 123I is preferred in patients with very poor thyroid function and in those with suspected retrosternal thyroid tissue. In addition, areas of increased 99mTc concentration should also be studied with 123I."} {"id": "PMID:1255251", "title": "Thyroid scanning with gallium-67 and cesium-131.", "content": "The roles of 131Cs and 67Ga in the evaluation of solitary thyroid nodules were investigated. Radionuclide scans were performed with 67Ga and 131I in 27 patients and with 131Cs and 131I in 43 patients. Gallium-67 detected only two of eight malignant nonfunctioning nodules and 131Cs detected one of three such nodules. The contribution of 131Cs and 67Ga to the preoperative identification of malignant thyroid lesions is of doubtful value.", "contents": "Thyroid scanning with gallium-67 and cesium-131. The roles of 131Cs and 67Ga in the evaluation of solitary thyroid nodules were investigated. Radionuclide scans were performed with 67Ga and 131I in 27 patients and with 131Cs and 131I in 43 patients. Gallium-67 detected only two of eight malignant nonfunctioning nodules and 131Cs detected one of three such nodules. The contribution of 131Cs and 67Ga to the preoperative identification of malignant thyroid lesions is of doubtful value."} {"id": "PMID:1255252", "title": "Abnormal 67Ga-citrate scan of the abdomen in tuberculous peritonitis: case report.", "content": "Tuberculous peritonitis in a 34-year-old alcoholic man was associated with an abnormal 67Ga-citrate scan of the abdomen. Repeated studies after thorough bowel cleansing revealed no change in the site and shape of the abnormality for 2--5 days after injection of the tracer. The inflammatory process may have been responsible for the abnormal scan.", "contents": "Abnormal 67Ga-citrate scan of the abdomen in tuberculous peritonitis: case report. Tuberculous peritonitis in a 34-year-old alcoholic man was associated with an abnormal 67Ga-citrate scan of the abdomen. Repeated studies after thorough bowel cleansing revealed no change in the site and shape of the abnormality for 2--5 days after injection of the tracer. The inflammatory process may have been responsible for the abnormal scan."} {"id": "PMID:1255253", "title": "Tumor model studies of 131I-tetracycline and other compounds.", "content": "Iodine-131-tetracycline (131I-TET) was prepared by allowing tetracycline hydrochloride to react with radioiodide in acidic methanol (labeling efficiency greater than 85%). This preparation was found to be stable at--4 degrees C for at least 72 hr. Some minimal in vivo breakdown did occur. The 131I-TET, 67Ga, and several 99mTc compounds were studied in a rat hepatoma model. The incorporation of the radiopharmaceuticals into the tumor occurred rapidly, with peak levels at 0.5 and 24 hr after injection for 131I-TET and 67Ga, respectively. The clearnace of the radiopharmaceutical from nonviable tumor was slower than for viable tumor, and by 72 hr after injection the greatest concentration of radioactivity appeared in the nonviable fraction. All normal tissues showed faster clearance than did tumor tissue, regardless of viability. Decreasing the quantity of 131I-TET injected increased the percent of uptake in the nonviable tumor tissue but had no effect on the viable tumor uptake. Of the 99mTc compounds studied, the phosphates developed the highest tumor-to-background ratios. Unfortunately these ratios were not as high as those achieved for 67Ga or 131I-TET.", "contents": "Tumor model studies of 131I-tetracycline and other compounds. Iodine-131-tetracycline (131I-TET) was prepared by allowing tetracycline hydrochloride to react with radioiodide in acidic methanol (labeling efficiency greater than 85%). This preparation was found to be stable at--4 degrees C for at least 72 hr. Some minimal in vivo breakdown did occur. The 131I-TET, 67Ga, and several 99mTc compounds were studied in a rat hepatoma model. The incorporation of the radiopharmaceuticals into the tumor occurred rapidly, with peak levels at 0.5 and 24 hr after injection for 131I-TET and 67Ga, respectively. The clearnace of the radiopharmaceutical from nonviable tumor was slower than for viable tumor, and by 72 hr after injection the greatest concentration of radioactivity appeared in the nonviable fraction. All normal tissues showed faster clearance than did tumor tissue, regardless of viability. Decreasing the quantity of 131I-TET injected increased the percent of uptake in the nonviable tumor tissue but had no effect on the viable tumor uptake. Of the 99mTc compounds studied, the phosphates developed the highest tumor-to-background ratios. Unfortunately these ratios were not as high as those achieved for 67Ga or 131I-TET."} {"id": "PMID:1255254", "title": "Circulation clearance rate of radioiodine during fibrinogen uptake tests.", "content": "Scintillation counts, following administration of 125I-labeled fibrinogen, were performed on the legs of medical and surgical patients. As part of the test procedure, precordial count rates were recorded and used in calculating the fibrinogen clearance rates. A short half-time for the circulating radioiodine was found to correlate well with the detection of venous thrombosis.", "contents": "Circulation clearance rate of radioiodine during fibrinogen uptake tests. Scintillation counts, following administration of 125I-labeled fibrinogen, were performed on the legs of medical and surgical patients. As part of the test procedure, precordial count rates were recorded and used in calculating the fibrinogen clearance rates. A short half-time for the circulating radioiodine was found to correlate well with the detection of venous thrombosis."} {"id": "PMID:1255255", "title": "Distribution and retention of 35S-sodium sulfate in man.", "content": "Measurements were made of the 35S content of tissues obtained from biopsies and autopsies made during and up to 6 months after treatment of chondrosarcoma or chordoma with carrier-free Na235SO4. Usually 70--90% of an intravenous dose was excreted in the urine during the first 3 days. The major component of the blood concentration had a biologic half-time of 0.4--0.7 days. The initial uptakes in chondrosarcoma, chordoma, and red bone marrow were high and nearly equal, but the rates of loss differed greatly. Uptake in epiphyseal cartilage was comparable to that in chondrosarcoma; uptake in other types of cartilage was lower, but subsequent loss was very slow. For an administered dose of 1 mCi per kilogram of body weight, the integrated radiation doses were 2.4 rads for blood, 33 rads for red bone marrow, 155 rads for chondrosarcoma, 49 rads for chordoma, and 135 rads for normal cartilage. Doses to muscle, skin, and fibrous tissue were 7--15 rads.", "contents": "Distribution and retention of 35S-sodium sulfate in man. Measurements were made of the 35S content of tissues obtained from biopsies and autopsies made during and up to 6 months after treatment of chondrosarcoma or chordoma with carrier-free Na235SO4. Usually 70--90% of an intravenous dose was excreted in the urine during the first 3 days. The major component of the blood concentration had a biologic half-time of 0.4--0.7 days. The initial uptakes in chondrosarcoma, chordoma, and red bone marrow were high and nearly equal, but the rates of loss differed greatly. Uptake in epiphyseal cartilage was comparable to that in chondrosarcoma; uptake in other types of cartilage was lower, but subsequent loss was very slow. For an administered dose of 1 mCi per kilogram of body weight, the integrated radiation doses were 2.4 rads for blood, 33 rads for red bone marrow, 155 rads for chondrosarcoma, 49 rads for chordoma, and 135 rads for normal cartilage. Doses to muscle, skin, and fibrous tissue were 7--15 rads."} {"id": "PMID:1255256", "title": "A new 80-lens oscilloscope camera for routine dynamic organ scintigraphy.", "content": "A simple, reliable, and cost-effective 80-lens photographic camera records dynamically from the oscilloscope of a scintillation camera without degradation of spatial resolution or data loss. Most physiologic events can be recorded completely and without interruption on a single 9 X 12-cm negative film as 40 sequential time-frames, using one of six available exposures per frame. In addition, 40 simultaneous sequential time-frames of four times the chosen duration may bracket a transient event with increased data density. The 80-lens camera has been used routinely for perfusion scintigraphy of brain, heart, liver, kidneys,and lungs with excellent results.", "contents": "A new 80-lens oscilloscope camera for routine dynamic organ scintigraphy. A simple, reliable, and cost-effective 80-lens photographic camera records dynamically from the oscilloscope of a scintillation camera without degradation of spatial resolution or data loss. Most physiologic events can be recorded completely and without interruption on a single 9 X 12-cm negative film as 40 sequential time-frames, using one of six available exposures per frame. In addition, 40 simultaneous sequential time-frames of four times the chosen duration may bracket a transient event with increased data density. The 80-lens camera has been used routinely for perfusion scintigraphy of brain, heart, liver, kidneys,and lungs with excellent results."} {"id": "PMID:1255257", "title": "Radiation dosimetry of 204Bi- and 206Bi-citrates.", "content": "The absorbed-radiation doses from 204Bi- and 206Bi-citrates to humans are calculated from available nuclear and biologic data in order to evaluate the relative radiation risk of these radionuclides. The calculations reveal that the radiation dose to the kidneys is reduced by a factor of 8 if 204Bi replaces 206Bi. This reduction suggests that 204Bi should be investigated further as a possible soft-tissue scanning agent.", "contents": "Radiation dosimetry of 204Bi- and 206Bi-citrates. The absorbed-radiation doses from 204Bi- and 206Bi-citrates to humans are calculated from available nuclear and biologic data in order to evaluate the relative radiation risk of these radionuclides. The calculations reveal that the radiation dose to the kidneys is reduced by a factor of 8 if 204Bi replaces 206Bi. This reduction suggests that 204Bi should be investigated further as a possible soft-tissue scanning agent."} {"id": "PMID:1255258", "title": "\"EAR\" artifact in brain scans.", "content": "The ear closest to the camera may be imaged in high-resolution lateral views of the brain as a structure anterior to the lateral sinus. The artifact can usually be eliminated by taping the auricle down. Artifacts such as this can be expected to become somewhat more of a problem as image resolution improves.", "contents": "\"EAR\" artifact in brain scans. The ear closest to the camera may be imaged in high-resolution lateral views of the brain as a structure anterior to the lateral sinus. The artifact can usually be eliminated by taping the auricle down. Artifacts such as this can be expected to become somewhat more of a problem as image resolution improves."} {"id": "PMID:1255259", "title": "Thyroid uptake of 131I: further comparisons of capsules and liquid preparations.", "content": "Comparisons were made of thyroid uptake of three commercially available preparations of 131I, using a double-blind design, in 125 patients with normal thyroid function. Uptakes with Squibb Iodotope Diagnostic capsules were significantly lower than those with Squibb Iodotope Oral liquid at 4 hr (p less than 0.01) and 24 hr (p less than 0.05) after ingestion in both the general population and in all patients less than 45 years of age. Uptakes of Radiocaps I-131 (Abbott Laboratories) and Iodotope Oral liquid were indistinguishable under identical conditions. Our findings indicate that interference with either absorption or metabolism of a pharmaceutical can result from the vehicle used to administer it.", "contents": "Thyroid uptake of 131I: further comparisons of capsules and liquid preparations. Comparisons were made of thyroid uptake of three commercially available preparations of 131I, using a double-blind design, in 125 patients with normal thyroid function. Uptakes with Squibb Iodotope Diagnostic capsules were significantly lower than those with Squibb Iodotope Oral liquid at 4 hr (p less than 0.01) and 24 hr (p less than 0.05) after ingestion in both the general population and in all patients less than 45 years of age. Uptakes of Radiocaps I-131 (Abbott Laboratories) and Iodotope Oral liquid were indistinguishable under identical conditions. Our findings indicate that interference with either absorption or metabolism of a pharmaceutical can result from the vehicle used to administer it."} {"id": "PMID:1255260", "title": "Bone accumulation of 99mTc-labeled leucocytes.", "content": "Leucocytes were separated from rats' blood by dextran sedimentation method and labeled with 99mTc-pertechnetate. A maximum labeling efficiency of 18.5% was achieved with the addition of 1 mg of stannous chloride. The labeled leucocytes were intact and viable and the 99mTc label was firm. Distribution studies in rats, 3 hr after injection of 99mTc-labeled leucocytes, showed 33% concentration in the mineral part of the bone, this being slightly lower than the 36.8% concentration in the liver. Technetium concentration in the bones due to a complex formed by various ingredients used for leucocyte labeling was excluded since negligible bone uptake was noted after injection of an incubated mixture of 99mTc and all ingredients except leucocytes. Also 51Cr-labeled leucocytes showed no localization in the bone. These studies indicate that 99mTc and intact leucocytes form some sort of complex which has an affinity for bone cortex.", "contents": "Bone accumulation of 99mTc-labeled leucocytes. Leucocytes were separated from rats' blood by dextran sedimentation method and labeled with 99mTc-pertechnetate. A maximum labeling efficiency of 18.5% was achieved with the addition of 1 mg of stannous chloride. The labeled leucocytes were intact and viable and the 99mTc label was firm. Distribution studies in rats, 3 hr after injection of 99mTc-labeled leucocytes, showed 33% concentration in the mineral part of the bone, this being slightly lower than the 36.8% concentration in the liver. Technetium concentration in the bones due to a complex formed by various ingredients used for leucocyte labeling was excluded since negligible bone uptake was noted after injection of an incubated mixture of 99mTc and all ingredients except leucocytes. Also 51Cr-labeled leucocytes showed no localization in the bone. These studies indicate that 99mTc and intact leucocytes form some sort of complex which has an affinity for bone cortex."} {"id": "PMID:1255261", "title": "Comparison of inulin, iothalamate, and 99mTc-DTPA for measurement of glomerular filtration rate.", "content": "Clearances of inulin, 125I-iothalamate, and 99mTc-Sn-DTPA were measured simultaneously in five mongrel dogs exhibiting a wide range of glomerular filtration rates (GFR). Standard constant-infusion inulin clearance was compared to radionuclide clearances after subcutaneous injection of the emitters mixed with aqueous epinephrine. All three substances were found to have virtually identical clearances. The accuracy, accessibility, low cost, low radiation hazard, and short half-life of 99mTc-Sn-DTPA make it an excellent substance for measuring GFR. The subcutaneous technique offers an accuracy comparable to the more difficult constant-infusion method.", "contents": "Comparison of inulin, iothalamate, and 99mTc-DTPA for measurement of glomerular filtration rate. Clearances of inulin, 125I-iothalamate, and 99mTc-Sn-DTPA were measured simultaneously in five mongrel dogs exhibiting a wide range of glomerular filtration rates (GFR). Standard constant-infusion inulin clearance was compared to radionuclide clearances after subcutaneous injection of the emitters mixed with aqueous epinephrine. All three substances were found to have virtually identical clearances. The accuracy, accessibility, low cost, low radiation hazard, and short half-life of 99mTc-Sn-DTPA make it an excellent substance for measuring GFR. The subcutaneous technique offers an accuracy comparable to the more difficult constant-infusion method."} {"id": "PMID:1255262", "title": "Rapid radioimmunoassay of triiodothyronine on Sephadex G-25 by the Ames kit.", "content": "A rapid kit method for the determination of serum triiodothyronine levels is described. The method was satisfactory in cases of thyrotoxicosis, but its lower sensitivity in euthyroid patients gave higher levels (range 2.3-3.3 nM/liter) than normally found. The kit would be of value as a rapid method (little over 3 hr) to screen patients suspected of early or T3 thyrotoxicosis.", "contents": "Rapid radioimmunoassay of triiodothyronine on Sephadex G-25 by the Ames kit. A rapid kit method for the determination of serum triiodothyronine levels is described. The method was satisfactory in cases of thyrotoxicosis, but its lower sensitivity in euthyroid patients gave higher levels (range 2.3-3.3 nM/liter) than normally found. The kit would be of value as a rapid method (little over 3 hr) to screen patients suspected of early or T3 thyrotoxicosis."} {"id": "PMID:1255264", "title": "Fluoride-selenium interaction in the hard and soft tissues of the rat.", "content": "The interaction of dietary fluoride and selenium in the hard and soft tissues of rats was studied by providing drinking solutions containing 50 ppm F, as NaF, alone or plus 1 or 3 ppm Se as one of the following selenium compounds: NaSeO3, Na2SeO4, DL-selenomethionine, or DL-selenocystine. The following parameters were measured: symptoms of selenium toxicity, soft tissue uptake of fluoride and selenium, histology of liver and kidney tissues, fluoride uptake into growing femur bones, and fluoride uptake onto calcified molar enamel. No evidence was found that fluoride interacted with any of the four selenium compounds.", "contents": "Fluoride-selenium interaction in the hard and soft tissues of the rat. The interaction of dietary fluoride and selenium in the hard and soft tissues of rats was studied by providing drinking solutions containing 50 ppm F, as NaF, alone or plus 1 or 3 ppm Se as one of the following selenium compounds: NaSeO3, Na2SeO4, DL-selenomethionine, or DL-selenocystine. The following parameters were measured: symptoms of selenium toxicity, soft tissue uptake of fluoride and selenium, histology of liver and kidney tissues, fluoride uptake into growing femur bones, and fluoride uptake onto calcified molar enamel. No evidence was found that fluoride interacted with any of the four selenium compounds."} {"id": "PMID:1255265", "title": "Studies on the 1alpha, 25-dihydroxycholecalciferol-like activity in a calcinogenic plant. Cestrum diurnum, in the chick.", "content": "Cestrum diurnum (day-blooming jessamine) has been proposed to cause calcinosis in horses and cattle in Florida. The present studies investigated some physiological properties of the plant, using the chick as the experimental animal. The inclusion of dried leaf powder in a rachitogenic diet restored intestinal calcium-binding protein synthesis (CaBP) and increased calcium absorption in the cholecalciferol-deficient chick. The estimated level of cholecalciferol-equivalents in the dried leaf was about 30,000 to 35,000 IU/kg. Most of the activity was extractable with methanol:chloroform (2:1), indicating that the major cholecalciferol-like component in C. diurnum was different from the water soluble factor(s) in Solanum malacoxylon. The time course of effect of C. diurnum extract in rachitic chicks was similar to that ot 1,25-dihydroxycholecalciferol but the former had a longer lag time. The strontium fed chick, in which the kidney 25-hydroxycholecalciferol-1alpha-hydroxylase is inhibited, responded to C. diurnum extract, confirming the 1alpha,25-dihydroxycholecalciferol-like character of the Cestrum factor. The extract also appeared to interact with the intestinal 1 alpha,25-dihydroxycholecalciferol cytosol receptor although this observation is preliminary. These findings indicate that the l alpha,25-dihydroxycholecalciferol-like principle in C. diurnum many cause excessive calcium and phosphate absorption leading to calcinosis.", "contents": "Studies on the 1alpha, 25-dihydroxycholecalciferol-like activity in a calcinogenic plant. Cestrum diurnum, in the chick. Cestrum diurnum (day-blooming jessamine) has been proposed to cause calcinosis in horses and cattle in Florida. The present studies investigated some physiological properties of the plant, using the chick as the experimental animal. The inclusion of dried leaf powder in a rachitogenic diet restored intestinal calcium-binding protein synthesis (CaBP) and increased calcium absorption in the cholecalciferol-deficient chick. The estimated level of cholecalciferol-equivalents in the dried leaf was about 30,000 to 35,000 IU/kg. Most of the activity was extractable with methanol:chloroform (2:1), indicating that the major cholecalciferol-like component in C. diurnum was different from the water soluble factor(s) in Solanum malacoxylon. The time course of effect of C. diurnum extract in rachitic chicks was similar to that ot 1,25-dihydroxycholecalciferol but the former had a longer lag time. The strontium fed chick, in which the kidney 25-hydroxycholecalciferol-1alpha-hydroxylase is inhibited, responded to C. diurnum extract, confirming the 1alpha,25-dihydroxycholecalciferol-like character of the Cestrum factor. The extract also appeared to interact with the intestinal 1 alpha,25-dihydroxycholecalciferol cytosol receptor although this observation is preliminary. These findings indicate that the l alpha,25-dihydroxycholecalciferol-like principle in C. diurnum many cause excessive calcium and phosphate absorption leading to calcinosis."} {"id": "PMID:1255266", "title": "Hydrogen production in the rat following ingestion of raffinose, stachyose and oligosaccharide-free bean residue.", "content": "Raffinose and stachyose were compared to cooked California Small White beans (CSW) containing 4% alpha-oligosaccharides (stachyose and raffinose) and to oligosaccharide-free CSW solids (residue from hexane and 70% ethanol extraction of CSW) as sources of hydrogen when ingested by rats maintained in life support systems. If the oligosaccharide content were the only hydrogen source in CSW, it would have had to be 25 times as potent as CSW, but raffinose was only five times and stachyose seven times as potent as CSW. Oligosaccharide-free residue was 0.4 to 0.5 as active as CSW. Hydrogen producing potencies of stachyose and raffinose were enhanced by feeding in combinations with residue. The increases in hydrogen production from the combinations were more than additive. Thus, CSW contains at least one 70% alcohol-insoluble substance which, in addition to the oligosaccharides, is essential to bring about quantitatively the physiological response to whole beans observed in rats.", "contents": "Hydrogen production in the rat following ingestion of raffinose, stachyose and oligosaccharide-free bean residue. Raffinose and stachyose were compared to cooked California Small White beans (CSW) containing 4% alpha-oligosaccharides (stachyose and raffinose) and to oligosaccharide-free CSW solids (residue from hexane and 70% ethanol extraction of CSW) as sources of hydrogen when ingested by rats maintained in life support systems. If the oligosaccharide content were the only hydrogen source in CSW, it would have had to be 25 times as potent as CSW, but raffinose was only five times and stachyose seven times as potent as CSW. Oligosaccharide-free residue was 0.4 to 0.5 as active as CSW. Hydrogen producing potencies of stachyose and raffinose were enhanced by feeding in combinations with residue. The increases in hydrogen production from the combinations were more than additive. Thus, CSW contains at least one 70% alcohol-insoluble substance which, in addition to the oligosaccharides, is essential to bring about quantitatively the physiological response to whole beans observed in rats."} {"id": "PMID:1255267", "title": "In vivo requirement for silicon in articular cartilage and connective tissue formation in the chick.", "content": "Studies were undertaken to determine further effects of silicon deficiency in the chick. The diet and experimental conditions were the same as those used in previous studies to demonstrate the essentiality of silicon for growth and development. Skeletal and other abnormalities involving glycosaminoglycans in formation of articular cartilage and comb connective tissue were found to be associated with silicon deficiency. The bones of 1 day-old deutectomized cockerels fed a silicon supplemented diet and killed at 4 weeks of age had significantly greater amounts of articular cartilage and water as compared with the silicon deficient group and also a greater proportion of hexosamine in the cartilage. The greater water content in bones of the silicon supplemented chicks coincided with a larger content of glycosaminoglycans in the articular cartilage. A similar relationship was obtained in cockerel comb. In addition to larger amounts of connective tissue and of total hexosamine in combs of the supplemented group, a higher percentage of hexosamine and a higher silicon content was found. These findings provide the first evidence for a requirement for silicon in articular cartilage and connective tissue formation and that the site of action of silicon is in the glycosaminoglycan-protein complexes of the ground substance.", "contents": "In vivo requirement for silicon in articular cartilage and connective tissue formation in the chick. Studies were undertaken to determine further effects of silicon deficiency in the chick. The diet and experimental conditions were the same as those used in previous studies to demonstrate the essentiality of silicon for growth and development. Skeletal and other abnormalities involving glycosaminoglycans in formation of articular cartilage and comb connective tissue were found to be associated with silicon deficiency. The bones of 1 day-old deutectomized cockerels fed a silicon supplemented diet and killed at 4 weeks of age had significantly greater amounts of articular cartilage and water as compared with the silicon deficient group and also a greater proportion of hexosamine in the cartilage. The greater water content in bones of the silicon supplemented chicks coincided with a larger content of glycosaminoglycans in the articular cartilage. A similar relationship was obtained in cockerel comb. In addition to larger amounts of connective tissue and of total hexosamine in combs of the supplemented group, a higher percentage of hexosamine and a higher silicon content was found. These findings provide the first evidence for a requirement for silicon in articular cartilage and connective tissue formation and that the site of action of silicon is in the glycosaminoglycan-protein complexes of the ground substance."} {"id": "PMID:1255268", "title": "In vitro uptake and metabolism of pteroylpolyglutamate by rat small intestine.", "content": "The digestion and cellular uptake of 14C-pteroylheptaglutamate (14C-PG-7) was studied using an isolated cell preparation from rat small intestine and by assay of folate conjugase (EC 3.4.23.10) in whole homogenates and brush border fractions of rat small intestinal mucosa. In the cell preparation, 14C-pteroylmonoglutamate (14C-PG-1), the principal degradation product of 14C-PG-7, was concentrated earlier in the cell fraction than in the extracellular fraction, while the concentrations equalized after 15 minutes. Incubation of cells with equimolar 14C-PG-7 and 3H-PG-1 was followed by a threefold greater cellular concentration of 14C-PG-1 than 3H-PG-1. In subcellular fractionation studies, folate conjugase was minimally present in the brush border relative to the supernatant fraction. These data suggest that 14C-PG-7 is transported into the epithelial cell of the intestinal mucosa prior to its hydrolysis by intracellular folate conjugase.", "contents": "In vitro uptake and metabolism of pteroylpolyglutamate by rat small intestine. The digestion and cellular uptake of 14C-pteroylheptaglutamate (14C-PG-7) was studied using an isolated cell preparation from rat small intestine and by assay of folate conjugase (EC 3.4.23.10) in whole homogenates and brush border fractions of rat small intestinal mucosa. In the cell preparation, 14C-pteroylmonoglutamate (14C-PG-1), the principal degradation product of 14C-PG-7, was concentrated earlier in the cell fraction than in the extracellular fraction, while the concentrations equalized after 15 minutes. Incubation of cells with equimolar 14C-PG-7 and 3H-PG-1 was followed by a threefold greater cellular concentration of 14C-PG-1 than 3H-PG-1. In subcellular fractionation studies, folate conjugase was minimally present in the brush border relative to the supernatant fraction. These data suggest that 14C-PG-7 is transported into the epithelial cell of the intestinal mucosa prior to its hydrolysis by intracellular folate conjugase."} {"id": "PMID:1255269", "title": "Decreased absorption of calcium, magnesium, zinc and phosphorus by humans due to increased fiber and phosphorus consumption as wheat bread.", "content": "During a 20 day period of high fiber consumption in the form of bread made partly from wheaten wholemeal, two men developed negative balances of calcium, magnesium, zinc and phosphorus due to increased fecal excretion of each element. The fecal losses correlated closely with fecal dry matter and phosphorus. Fecal dry matter, in turn, was directly proportional to fecal fiber excretion. Balances of nitrogen remained positive. Mineral elements were well-utilized by the same subjects during a 20-day period of white bread consumption.", "contents": "Decreased absorption of calcium, magnesium, zinc and phosphorus by humans due to increased fiber and phosphorus consumption as wheat bread. During a 20 day period of high fiber consumption in the form of bread made partly from wheaten wholemeal, two men developed negative balances of calcium, magnesium, zinc and phosphorus due to increased fecal excretion of each element. The fecal losses correlated closely with fecal dry matter and phosphorus. Fecal dry matter, in turn, was directly proportional to fecal fiber excretion. Balances of nitrogen remained positive. Mineral elements were well-utilized by the same subjects during a 20-day period of white bread consumption."} {"id": "PMID:1255270", "title": "Cholesterol turnover and tissue distribution in the guinea pig in response to dietary cholesterol.", "content": "Cholesterol turnover and tissue cholesterol distribution were studied in guinea pigs fed either a control diet or one containing 0.1% cholesterol. Dietary cholesterol caused a significant increase in the cholesterol concentration in liver, red blood cells and small intestine, but not in plasma. Most of the increase in total body cholesterol could be accounted for as an increase in liver esterified cholesterol content. Feeding the 0.1% cholesterol-containing diet did not significantly change either the absorption of an oral dose of tracer cholesterol or the endogenous cholesterol synthesis rate. Steady state cholesterol input-output rate and total traced mass of cholesterol were significantly greater, and mean transit time was significantly longer in the animals fed the cholesterol containing diet. These data suggest that the maintenance of cholesterol homeostasis in the nonhypercholesterolemic cholesterol-fed guinea pig depends on liver accumulation of esterified cholesterol as well as on increased output of cholesterol.", "contents": "Cholesterol turnover and tissue distribution in the guinea pig in response to dietary cholesterol. Cholesterol turnover and tissue cholesterol distribution were studied in guinea pigs fed either a control diet or one containing 0.1% cholesterol. Dietary cholesterol caused a significant increase in the cholesterol concentration in liver, red blood cells and small intestine, but not in plasma. Most of the increase in total body cholesterol could be accounted for as an increase in liver esterified cholesterol content. Feeding the 0.1% cholesterol-containing diet did not significantly change either the absorption of an oral dose of tracer cholesterol or the endogenous cholesterol synthesis rate. Steady state cholesterol input-output rate and total traced mass of cholesterol were significantly greater, and mean transit time was significantly longer in the animals fed the cholesterol containing diet. These data suggest that the maintenance of cholesterol homeostasis in the nonhypercholesterolemic cholesterol-fed guinea pig depends on liver accumulation of esterified cholesterol as well as on increased output of cholesterol."} {"id": "PMID:1255271", "title": "Activity of L-cysteinesulfinate carboxy-lyase and persulfurase in livers of rats fed different levels of sulfate and cysteine.", "content": "Activity of L-cysteinesulfinate carboxy-lyase (CSC) and persulfurase was measured in livers of rats fed 15% casein diets supplemented with (1) 0.53% cysteine, (2) 0.40% cysteine, (3) 0.40% cysteine + 0.10% sulfate, (4) 0.42% sulfate, or (5) 0.42% sulfate + 0.40% cysteine. The diets were fed to adult rats for 1 week and to weanling rats for periods of 1 and 4 weeks. At the end of each feeding period, the highest CSC activity was detected in livers from animals fed diet 4, but no differences in CSC activity were detected among livers from the other four groups. Persulfurase activity did not differ significantly among those weanling or adult rats fed the diets for 1 week but was lower among those fed diet 4 than diet 5 for 4 weeks. The acitivity patterns did not parallel those of taurine excretion or conjugation observed previously among rats fed the same diets, and may indicate that factors other than taurine synthesis and ingestion control those processes.", "contents": "Activity of L-cysteinesulfinate carboxy-lyase and persulfurase in livers of rats fed different levels of sulfate and cysteine. Activity of L-cysteinesulfinate carboxy-lyase (CSC) and persulfurase was measured in livers of rats fed 15% casein diets supplemented with (1) 0.53% cysteine, (2) 0.40% cysteine, (3) 0.40% cysteine + 0.10% sulfate, (4) 0.42% sulfate, or (5) 0.42% sulfate + 0.40% cysteine. The diets were fed to adult rats for 1 week and to weanling rats for periods of 1 and 4 weeks. At the end of each feeding period, the highest CSC activity was detected in livers from animals fed diet 4, but no differences in CSC activity were detected among livers from the other four groups. Persulfurase activity did not differ significantly among those weanling or adult rats fed the diets for 1 week but was lower among those fed diet 4 than diet 5 for 4 weeks. The acitivity patterns did not parallel those of taurine excretion or conjugation observed previously among rats fed the same diets, and may indicate that factors other than taurine synthesis and ingestion control those processes."} {"id": "PMID:1255272", "title": "Vitamin A metabolism during the repletion of zinc deficient rats.", "content": "The experiments reported here were designed to determine if the low plasma vitamin A levels observed in zinc deficient rats are reversible as well as to examine the time required for any response. In experiment 1, rats previously zinc deficient were repleted for 6 days with a zinc sufficient diet, fed either ad libitum, or pair-fed the amount consumed by a zinc deficient group. After repletion, plasma vitamin A concentration for the zinc sufficient group returned to within normal range while the pair-fed group had a plasma vitamin A concentration intermediate between the zinc sufficient ad libitum and zinc deficient groups. The zinc sufficient ad libitum group had a lower concentration but higher total liver content of vitamin A than the other two groups. In experiment 2, the response of zinc deficient rats to intraperitoneal zinc repletion was examined daily for 7 days. There was a 3 day lag period before plasma vitamin A began to increase significantly following zinc treatment. By the fifth day, plasma vitamin A concentration increased to within the normal range. The data suggest that adequate food intake as well as zinc appears necessary to totally reverse low plasma vitamin A concentrations in zinc deficiency. Possible mechanisms are discussed.", "contents": "Vitamin A metabolism during the repletion of zinc deficient rats. The experiments reported here were designed to determine if the low plasma vitamin A levels observed in zinc deficient rats are reversible as well as to examine the time required for any response. In experiment 1, rats previously zinc deficient were repleted for 6 days with a zinc sufficient diet, fed either ad libitum, or pair-fed the amount consumed by a zinc deficient group. After repletion, plasma vitamin A concentration for the zinc sufficient group returned to within normal range while the pair-fed group had a plasma vitamin A concentration intermediate between the zinc sufficient ad libitum and zinc deficient groups. The zinc sufficient ad libitum group had a lower concentration but higher total liver content of vitamin A than the other two groups. In experiment 2, the response of zinc deficient rats to intraperitoneal zinc repletion was examined daily for 7 days. There was a 3 day lag period before plasma vitamin A began to increase significantly following zinc treatment. By the fifth day, plasma vitamin A concentration increased to within the normal range. The data suggest that adequate food intake as well as zinc appears necessary to totally reverse low plasma vitamin A concentrations in zinc deficiency. Possible mechanisms are discussed."} {"id": "PMID:1255273", "title": "Effect of dietary fat on fluoride absorption and tissue fluoride retention in rats.", "content": "The effect of dietary fat on fluoride toxicity was investigated in rats fed isoenergetic diets with graded levels of fat (0, 10%, 30% or 50% of energy) containing 400 ppm fluoride. Growth rate was depressed in all groups receiving fluoride but most severely in the 50% dietary fat group. Plasma, liver and femur fluoride concentrations were increased by increasing dietary fat. This was apparently due to increased absorption of fluoride, since urinary fluoride increased and fecal fluoride excretion decreased as fat intake was elevated. The enhancement of fluoride absorption by fat is believed to be due to the delaying effect of fat and fluoride on gastric emptying, thereby allowing more time for the fluoride to be absorbed from the stomach.", "contents": "Effect of dietary fat on fluoride absorption and tissue fluoride retention in rats. The effect of dietary fat on fluoride toxicity was investigated in rats fed isoenergetic diets with graded levels of fat (0, 10%, 30% or 50% of energy) containing 400 ppm fluoride. Growth rate was depressed in all groups receiving fluoride but most severely in the 50% dietary fat group. Plasma, liver and femur fluoride concentrations were increased by increasing dietary fat. This was apparently due to increased absorption of fluoride, since urinary fluoride increased and fecal fluoride excretion decreased as fat intake was elevated. The enhancement of fluoride absorption by fat is believed to be due to the delaying effect of fat and fluoride on gastric emptying, thereby allowing more time for the fluoride to be absorbed from the stomach."} {"id": "PMID:1255276", "title": "Standardized mortality ratios and the \"healthy worker effect\": Scratching beneath the surface.", "content": "The age-standardized mortality ratio (SMR) is a relative index of mortality, expressing the mortality experience of the study population relative to that of a comparison (\"standard\") population. With the general population as the \"standard\", the SMR for an occupational population will underestimate the mortality experience of that latter population (since it comprises individuals necessarily healthy enough to be employable --and whose mortality risk is therefore initially lower than the general population average). However, this \"healthy worker effect\" does not equally to all groups within the study population. Therefore, if one attempts to adjust for this effect, the summary nature of the SMR must be recognized, and allowance must be made for variation in the healthy worker effect between different age groups, different races, different work-status groups, different causes of death, and different elapsed-time periods of observation.", "contents": "Standardized mortality ratios and the \"healthy worker effect\": Scratching beneath the surface. The age-standardized mortality ratio (SMR) is a relative index of mortality, expressing the mortality experience of the study population relative to that of a comparison (\"standard\") population. With the general population as the \"standard\", the SMR for an occupational population will underestimate the mortality experience of that latter population (since it comprises individuals necessarily healthy enough to be employable --and whose mortality risk is therefore initially lower than the general population average). However, this \"healthy worker effect\" does not equally to all groups within the study population. Therefore, if one attempts to adjust for this effect, the summary nature of the SMR must be recognized, and allowance must be made for variation in the healthy worker effect between different age groups, different races, different work-status groups, different causes of death, and different elapsed-time periods of observation."} {"id": "PMID:1255278", "title": "Determinants of mortality in an industrial population.", "content": "Many epidemiological problems are encountered in studies of mortality experience in industrial populations. The current study was undertaken to develop background data for a large chemical manufacturing company with emphasis on differentials in mortality associated with preselection factors, socioeconomic status, and general job categories. Statistically significant differences were observed in the industrial cohort with respect to socioeconomic level and job category. Differences between the industrial population and the corresponding US white male population were also noted. Findings of this study suggest additional avenues of investigative work for epidemiologists and clinicians concerned with the well being of employee groups in various industries.", "contents": "Determinants of mortality in an industrial population. Many epidemiological problems are encountered in studies of mortality experience in industrial populations. The current study was undertaken to develop background data for a large chemical manufacturing company with emphasis on differentials in mortality associated with preselection factors, socioeconomic status, and general job categories. Statistically significant differences were observed in the industrial cohort with respect to socioeconomic level and job category. Differences between the industrial population and the corresponding US white male population were also noted. Findings of this study suggest additional avenues of investigative work for epidemiologists and clinicians concerned with the well being of employee groups in various industries."} {"id": "PMID:1255279", "title": "Mortality among rubber workers: Relationship to specific jobs.", "content": "This study has examined the ten-year mortality in a single-plant population of 6678 male rubber workers, in terms of the association of specific causes of death with a history of having worked in certain categories of jobs within the rubber industry. The work-histories of individual study subjects were analyzed, in detail, for all workers dying of selected causes of death. Comparison was made with the work-histories of a 22% age-stratified random sample of the total population. Age-adjusted exposure ratios (Tables 3 and 4) were calculated for all nine case groups in all 16 work areas, using differing exposure criteria (i.e. duration and calendar period). These ratios provide an approximation of the increased mortality risk associated with particular work areas. The risk ratios (with their associated confidence intervals), in Table 5, provide more rigorous estimates of these instances of increased mortality risk. For each cause of death studied, there were statistically significant associations with several work areas. For the cancers, the strongest associations tended to be with work areas at the front end of the production line (especially compounding and mixing), where the likelihood of contact with dusts, chemical ingredients, and vapors containing the early reaction byproducts, is high. The reclaim operation and the synthetic plant were each associated with several cancers (respiratory and bladder, and stomach and lymphato-hematopoietic cancers, respectively). The lymphatic leukemias were associated with solvent-exposure areas, especially inspection, finishing, and repair. Ischemic heart disease deaths, at ages 40-54, were strongly associated with having worked in extrusion and tread cementing, and in the synthetic plant. Deaths from diabetes mellitus were strongly associated with the janitoring-trucking category, and with jobs in the inspection, finishing and repair area. These observed associations, calculated after controlling for the variables sex and age, were apparently not due to confounding by smoking and race differences between work areas. The role of selective transfer of sick individuals (into, say janitoring or trucking) warrants further investigation. However, this mechanism is unlikely to be involved in the great majority of the observed associations. Another possible source of spurious inferences of increased risk would be correlation, within work-histories, between two job categories, one of which actually involved increased risk, while the other did not. Such associations could occur if certain job sequency trends existed within this working population. (Preliminary analyses indicate that this likelihood is not great; however, further analysis is planned.) Detailed study of specific environmental agents, historically and cross-sectionally, is currently underway, in an attempt to identify the work-environment agents responsible for the associations reported here.", "contents": "Mortality among rubber workers: Relationship to specific jobs. This study has examined the ten-year mortality in a single-plant population of 6678 male rubber workers, in terms of the association of specific causes of death with a history of having worked in certain categories of jobs within the rubber industry. The work-histories of individual study subjects were analyzed, in detail, for all workers dying of selected causes of death. Comparison was made with the work-histories of a 22% age-stratified random sample of the total population. Age-adjusted exposure ratios (Tables 3 and 4) were calculated for all nine case groups in all 16 work areas, using differing exposure criteria (i.e. duration and calendar period). These ratios provide an approximation of the increased mortality risk associated with particular work areas. The risk ratios (with their associated confidence intervals), in Table 5, provide more rigorous estimates of these instances of increased mortality risk. For each cause of death studied, there were statistically significant associations with several work areas. For the cancers, the strongest associations tended to be with work areas at the front end of the production line (especially compounding and mixing), where the likelihood of contact with dusts, chemical ingredients, and vapors containing the early reaction byproducts, is high. The reclaim operation and the synthetic plant were each associated with several cancers (respiratory and bladder, and stomach and lymphato-hematopoietic cancers, respectively). The lymphatic leukemias were associated with solvent-exposure areas, especially inspection, finishing, and repair. Ischemic heart disease deaths, at ages 40-54, were strongly associated with having worked in extrusion and tread cementing, and in the synthetic plant. Deaths from diabetes mellitus were strongly associated with the janitoring-trucking category, and with jobs in the inspection, finishing and repair area. These observed associations, calculated after controlling for the variables sex and age, were apparently not due to confounding by smoking and race differences between work areas. The role of selective transfer of sick individuals (into, say janitoring or trucking) warrants further investigation. However, this mechanism is unlikely to be involved in the great majority of the observed associations. Another possible source of spurious inferences of increased risk would be correlation, within work-histories, between two job categories, one of which actually involved increased risk, while the other did not. Such associations could occur if certain job sequency trends existed within this working population. (Preliminary analyses indicate that this likelihood is not great; however, further analysis is planned.) Detailed study of specific environmental agents, historically and cross-sectionally, is currently underway, in an attempt to identify the work-environment agents responsible for the associations reported here."} {"id": "PMID:1255281", "title": "Chloromethyl ethers, cigarettes, cough and cancer.", "content": "Beginning in 1963 a 10-year prospective study of 125 chemical workers was carried out by periodic screening for five years and follow-up for an additional five years. Eighty-eight men were exposed to chloromethyl ethers in varying cumulative doses estimates by retrospective rating. They were divided into three groups by degree of exposure. Age distribution was similar in all groups but the proportion of current heavy cigarette smokers at the start of observation decreased with increasing chemical exposure. The prevalence of chronic cough showed a dose-response relationship to both smoking and chemical exposure. The end-expiratory flow rate was below 60% of predicted in about one-third of the exposed men compared to only 6% of unexposed men and the frequency of such low rates was dose-related to cigarette smoking. During the five-year periodic screening study the prevalence of chronic cough decreased and the prevalence of dyspnea increased while chemical exposure was falling. The 10-year incidence of lung cancer was dose-related to chemical exposure but inversely related to smoking habits. All cancers were small-cell carcinomas, occurred in men younger than 55, and had an induction-latent period of 10 to 24 years. The 10-year mortality rate in this group of workers was 2.7 times expected and lung cancer accounted for the excess number of deaths.", "contents": "Chloromethyl ethers, cigarettes, cough and cancer. Beginning in 1963 a 10-year prospective study of 125 chemical workers was carried out by periodic screening for five years and follow-up for an additional five years. Eighty-eight men were exposed to chloromethyl ethers in varying cumulative doses estimates by retrospective rating. They were divided into three groups by degree of exposure. Age distribution was similar in all groups but the proportion of current heavy cigarette smokers at the start of observation decreased with increasing chemical exposure. The prevalence of chronic cough showed a dose-response relationship to both smoking and chemical exposure. The end-expiratory flow rate was below 60% of predicted in about one-third of the exposed men compared to only 6% of unexposed men and the frequency of such low rates was dose-related to cigarette smoking. During the five-year periodic screening study the prevalence of chronic cough decreased and the prevalence of dyspnea increased while chemical exposure was falling. The 10-year incidence of lung cancer was dose-related to chemical exposure but inversely related to smoking habits. All cancers were small-cell carcinomas, occurred in men younger than 55, and had an induction-latent period of 10 to 24 years. The 10-year mortality rate in this group of workers was 2.7 times expected and lung cancer accounted for the excess number of deaths."} {"id": "PMID:1255301", "title": "The pathogenesis of lupinosis in the rat.", "content": "The morphological, histochemical and biochemical changes in the liver of rats challenged with a single intraperitoneal injection of the toxin of lupinosis were investigated. The resulting injury is biphasic. The initial non-specific phase lasts for a few days, affects mainly the centrilobular region and is characterised by mitochondrial swelling, lipid accummulation and autophagosome formation. In addition, the hepatic concentrations of OCT, LDH, SDH, and AST fall while that for ALP increase. This is accompanied by a rise in the serum concentration of many of these enzymes. The second phase lasts longer and is characterised by phenomena indicative of abnormalities in hepatocytic division. Normal and abnormal metaphase as well as multinucleated hepatocytes falls. The possibility that the toxin of lupinosis interferes with microtubular units is considered.", "contents": "The pathogenesis of lupinosis in the rat. The morphological, histochemical and biochemical changes in the liver of rats challenged with a single intraperitoneal injection of the toxin of lupinosis were investigated. The resulting injury is biphasic. The initial non-specific phase lasts for a few days, affects mainly the centrilobular region and is characterised by mitochondrial swelling, lipid accummulation and autophagosome formation. In addition, the hepatic concentrations of OCT, LDH, SDH, and AST fall while that for ALP increase. This is accompanied by a rise in the serum concentration of many of these enzymes. The second phase lasts longer and is characterised by phenomena indicative of abnormalities in hepatocytic division. Normal and abnormal metaphase as well as multinucleated hepatocytes falls. The possibility that the toxin of lupinosis interferes with microtubular units is considered."} {"id": "PMID:1255302", "title": "Vascular infiltration in benign breast disease.", "content": "Infiltration of the walls of blood vessels by mammary epithelium was found in two cases of sclerosing adenosis. Survey of a series of cases of sclerosing adenosis and severe epitheliosis revealed a 10 per cent incidence of vascular infiltration. Usually only a single vein was involved but in the propositus an artery and two veins were infiltrated. The findings highlight the infiltrative propensities of sclerosing adenosis, already recognised as infiltrating nerve sheaths. The vascular lesions appear to be benign structurally and this is borne out by the clinical behaviour.", "contents": "Vascular infiltration in benign breast disease. Infiltration of the walls of blood vessels by mammary epithelium was found in two cases of sclerosing adenosis. Survey of a series of cases of sclerosing adenosis and severe epitheliosis revealed a 10 per cent incidence of vascular infiltration. Usually only a single vein was involved but in the propositus an artery and two veins were infiltrated. The findings highlight the infiltrative propensities of sclerosing adenosis, already recognised as infiltrating nerve sheaths. The vascular lesions appear to be benign structurally and this is borne out by the clinical behaviour."} {"id": "PMID:1255303", "title": "Juvenile astrocytomas with subarachnoid spread.", "content": "The surgical and necropsy findings in five cases of extracerebellar astrocytoma showing subarachnoid spread and invasion of surrounding structures are presented. The patients varied in age from 6 to 23 yr, and all died of the effects of the tumour within 20 mth of the onset of the symptoms. In each case histological examination reveals areas of piloid astrocytes, but these show varying degrees of nuclear abnormalities. Oligodendrocytomatous foci are also seen in some cases. It is suggested that nuclear pleomorphism or oligodendrocytomatous areas indicate a poor prognosis in an otherwise typical juvenile astrocytoma, and may be associated with a partly anaplastic tumour.", "contents": "Juvenile astrocytomas with subarachnoid spread. The surgical and necropsy findings in five cases of extracerebellar astrocytoma showing subarachnoid spread and invasion of surrounding structures are presented. The patients varied in age from 6 to 23 yr, and all died of the effects of the tumour within 20 mth of the onset of the symptoms. In each case histological examination reveals areas of piloid astrocytes, but these show varying degrees of nuclear abnormalities. Oligodendrocytomatous foci are also seen in some cases. It is suggested that nuclear pleomorphism or oligodendrocytomatous areas indicate a poor prognosis in an otherwise typical juvenile astrocytoma, and may be associated with a partly anaplastic tumour."} {"id": "PMID:1255304", "title": "Tumours arising in skeletal muscle in adults.", "content": "A review has been made of 30 cases of tumours arising in skeletal muscle seen over a 21-yr period (1954-74) in the Department of Pathology, Western General Hospital, Edinburgh. There were 17 females and 13 males in the series. The age range was 15 to 88 yr. The commonest site was thigh muscles (18 cases). Seven of the 14 benign tumours were myxomas: the other benign tumours included two solitary myositis ossificans, two haemangiomas and three lipomas. The three tumours which might be considered as being of borderline malignancy were two haemangiopericytomas and one desmoid tumour. There were 13 malignant tumours in the series: five fibrosarcomas, five liposarcomas, two rhabdomyosarcomas and one undifferentiated (pleomorphic) sarcoma. The average length of survival of the nine patients with malignant tumours who have died was only 15 mth. The fibrosarcomas in particular behaved in a highly malignant fashion. These 13 intramuscular sarcomas accounted for approximately 11 per cent, of all mesenchymal (non-lymphoid) sarcomas seen during the period of study.", "contents": "Tumours arising in skeletal muscle in adults. A review has been made of 30 cases of tumours arising in skeletal muscle seen over a 21-yr period (1954-74) in the Department of Pathology, Western General Hospital, Edinburgh. There were 17 females and 13 males in the series. The age range was 15 to 88 yr. The commonest site was thigh muscles (18 cases). Seven of the 14 benign tumours were myxomas: the other benign tumours included two solitary myositis ossificans, two haemangiomas and three lipomas. The three tumours which might be considered as being of borderline malignancy were two haemangiopericytomas and one desmoid tumour. There were 13 malignant tumours in the series: five fibrosarcomas, five liposarcomas, two rhabdomyosarcomas and one undifferentiated (pleomorphic) sarcoma. The average length of survival of the nine patients with malignant tumours who have died was only 15 mth. The fibrosarcomas in particular behaved in a highly malignant fashion. These 13 intramuscular sarcomas accounted for approximately 11 per cent, of all mesenchymal (non-lymphoid) sarcomas seen during the period of study."} {"id": "PMID:1255305", "title": "Cytotoxic carcinogeneic response to monocrotaline pyrrole.", "content": "The cytotoxic and carcinogenic effects of MCP, the possible proximate metabolite of the alkaloid monocrotaline, were investigated in rats by the subcutaneous route. Sequential of MCP subcutaneously produced an acute inflammatory reaction with necrosis of the local tissue. A slight delay in connective-tissue repair occurred and markedly enlarged fibroblasts were a distinctive feature of the lesion. Four injection site sarcomas were produced after repeated injection of 60 mug MCP in tricaprylin. Injection of 30 mug MCP in tricaprylin twice weekly gave rise to three local tumours. Controls injected repeatedly with tricaprylin developed two sarcomas at the injection site. The significance of these findings is discussed and it is concluded that MCP is undoubtedly cytotoxic but that its carcinogenic potency is equivocal.", "contents": "Cytotoxic carcinogeneic response to monocrotaline pyrrole. The cytotoxic and carcinogenic effects of MCP, the possible proximate metabolite of the alkaloid monocrotaline, were investigated in rats by the subcutaneous route. Sequential of MCP subcutaneously produced an acute inflammatory reaction with necrosis of the local tissue. A slight delay in connective-tissue repair occurred and markedly enlarged fibroblasts were a distinctive feature of the lesion. Four injection site sarcomas were produced after repeated injection of 60 mug MCP in tricaprylin. Injection of 30 mug MCP in tricaprylin twice weekly gave rise to three local tumours. Controls injected repeatedly with tricaprylin developed two sarcomas at the injection site. The significance of these findings is discussed and it is concluded that MCP is undoubtedly cytotoxic but that its carcinogenic potency is equivocal."} {"id": "PMID:1255306", "title": "The pathogenesis of experimental pulmonary aspergillosis in normal and cortisone-treated rats.", "content": "Normal outbred adult Wistar rats were resistant to infection with intratracheally administered viable spores of Aspergillus fumigatus although although they developed a subacute interestitial pneumonia. While the lesions were more severe in animals immune suppressed with Azathioprine (immuran) there was no evidence of hyphal growth in the pulmonary tissue. Significant histological involvement was found only in those animals receiving repeared subcutaneous injections of cortisone and multiple intratracheal injections of spores. Granulomatous lesions were scattered throughout the parenchyma of the lung, and many eroded the walls of adjoining bronchioles permitting entry of the material in the necrotic centre of the granuloma into the lumen of the bronchiole.", "contents": "The pathogenesis of experimental pulmonary aspergillosis in normal and cortisone-treated rats. Normal outbred adult Wistar rats were resistant to infection with intratracheally administered viable spores of Aspergillus fumigatus although although they developed a subacute interestitial pneumonia. While the lesions were more severe in animals immune suppressed with Azathioprine (immuran) there was no evidence of hyphal growth in the pulmonary tissue. Significant histological involvement was found only in those animals receiving repeared subcutaneous injections of cortisone and multiple intratracheal injections of spores. Granulomatous lesions were scattered throughout the parenchyma of the lung, and many eroded the walls of adjoining bronchioles permitting entry of the material in the necrotic centre of the granuloma into the lumen of the bronchiole."} {"id": "PMID:1255307", "title": "Nephrotoxic action of rattlesnake and sea snake venoms: an electron-microscopic study.", "content": "The fine structure of renal corpuscles and proximal convoluted tubules of the right kidneys of Suiss mice were studied 9 hr after the injection of the venom of Crotalus atrox (Western diamond-back rattlesnake) or the venom of Laticauda semifasciata (broad-banded blue sea snake). Rattlesnake envenomation resulted in several ultrastructural changes in the renal corpuscles and proximal convoluted tubules. Visceral epithelial changes included intracellular oedema, blebbing, vesiculations, the formation of microvillus projections and dilatation of the endoplasmic reticulum and mitochondria. Changes in the parietal epithelium were similar except that no microvillus projections were noted. Mesangiolysis was a consistent finding. Collagenous fibrils were very prominent in the lysed areas of the mesangial cells. Increased numbers of lysosome-related structures were noted in the proximal convoluted tubule cells. Most of the nuclear cisternae of the cells of the renal corpuscles and proximal convoluted tubules were greatly dilated. Sea snake envenomation resulted in focal organellar swelling and focal intracellular oedema of the visceral epithelium. This venom did not affect the cells of the proximal convoluted tubule. The presence of light and dark visceral epithelial cells has been a consistent finding for both the control and the environmated groups.", "contents": "Nephrotoxic action of rattlesnake and sea snake venoms: an electron-microscopic study. The fine structure of renal corpuscles and proximal convoluted tubules of the right kidneys of Suiss mice were studied 9 hr after the injection of the venom of Crotalus atrox (Western diamond-back rattlesnake) or the venom of Laticauda semifasciata (broad-banded blue sea snake). Rattlesnake envenomation resulted in several ultrastructural changes in the renal corpuscles and proximal convoluted tubules. Visceral epithelial changes included intracellular oedema, blebbing, vesiculations, the formation of microvillus projections and dilatation of the endoplasmic reticulum and mitochondria. Changes in the parietal epithelium were similar except that no microvillus projections were noted. Mesangiolysis was a consistent finding. Collagenous fibrils were very prominent in the lysed areas of the mesangial cells. Increased numbers of lysosome-related structures were noted in the proximal convoluted tubule cells. Most of the nuclear cisternae of the cells of the renal corpuscles and proximal convoluted tubules were greatly dilated. Sea snake envenomation resulted in focal organellar swelling and focal intracellular oedema of the visceral epithelium. This venom did not affect the cells of the proximal convoluted tubule. The presence of light and dark visceral epithelial cells has been a consistent finding for both the control and the environmated groups."} {"id": "PMID:1255309", "title": "Prospective evaluation of treatment of Hemophilus influenzae meningitis.", "content": "Fifty children with Hemophilus influenzae meningitis have been enrolled in a prospective study. Patients were randomly assigned chloramphenicol or ampicillin treatment; there were no significant differences between groups in other respects. Countercurrent immunoelectrophoresis proved to be a valuable tool for rapid diagnosis of the causative agent even in pretreated patients. Increasing quantities of capsular polyribosephosphate antigen detected in the initial cerebrospinal fluid correlated significantly (r=0.62419; p less than 0.01) with early and late sequelae of meningitis. None of the patients died. Severe and persistent neurologic or intellectual deficits were noted in four (8%) of the children, and an additional 14 (28%) had IQ scores between 70 and 90. The presence of bactericidal antibody in serum was not protective. Anti-PRP antibody generally was not present in acute serum specimens and irrespective of the quantity of antigenic stimulus provided by the disease was nondetectable in 21 of 24 children less than 17 months of age following recovery.", "contents": "Prospective evaluation of treatment of Hemophilus influenzae meningitis. Fifty children with Hemophilus influenzae meningitis have been enrolled in a prospective study. Patients were randomly assigned chloramphenicol or ampicillin treatment; there were no significant differences between groups in other respects. Countercurrent immunoelectrophoresis proved to be a valuable tool for rapid diagnosis of the causative agent even in pretreated patients. Increasing quantities of capsular polyribosephosphate antigen detected in the initial cerebrospinal fluid correlated significantly (r=0.62419; p less than 0.01) with early and late sequelae of meningitis. None of the patients died. Severe and persistent neurologic or intellectual deficits were noted in four (8%) of the children, and an additional 14 (28%) had IQ scores between 70 and 90. The presence of bactericidal antibody in serum was not protective. Anti-PRP antibody generally was not present in acute serum specimens and irrespective of the quantity of antigenic stimulus provided by the disease was nondetectable in 21 of 24 children less than 17 months of age following recovery."} {"id": "PMID:1255310", "title": "Detection of bacterial antigen in pleural fluid by counterimmunoelectrophoresis.", "content": "Pleural fluid specimens from 87 patients were studied using counterimmunoelectrophoresis with pneumococcal, staphylococcal, and Hemophilus influenza b antisera. This method compared favorably with traditional bacteriologic methods and in addition provided a presumptive etiologic diagnosis in more than half of the specimens with negative bacterial cultures. One cross-reaction between H. influenza b antiserum and a pleural fluid specimen with an Escherichia coli isolate was observed.", "contents": "Detection of bacterial antigen in pleural fluid by counterimmunoelectrophoresis. Pleural fluid specimens from 87 patients were studied using counterimmunoelectrophoresis with pneumococcal, staphylococcal, and Hemophilus influenza b antisera. This method compared favorably with traditional bacteriologic methods and in addition provided a presumptive etiologic diagnosis in more than half of the specimens with negative bacterial cultures. One cross-reaction between H. influenza b antiserum and a pleural fluid specimen with an Escherichia coli isolate was observed."} {"id": "PMID:1255311", "title": "Hepatitis B virus infection in the Wiskott-Aldrich syndrome.", "content": "Testing of paired serum samples of 12 children with the Wiskott-Aldrich syndrome for the presence of hepatitis B surface antigen (HBsAg) antibody to HB, Ag, and antibody to the hepatitis B core antigen revealed evidence of hepatitis B virus infection in three. None of the three, however, developed overt clinical hepatitis or the chronic HBsAg carrier state. These data suggest that the immunologic defects seen in the Wiskott-Aldrich syndrome permit adequate immune responses to the hepatitis B virus and do not predispose to the chronic HBsAg carrier state.", "contents": "Hepatitis B virus infection in the Wiskott-Aldrich syndrome. Testing of paired serum samples of 12 children with the Wiskott-Aldrich syndrome for the presence of hepatitis B surface antigen (HBsAg) antibody to HB, Ag, and antibody to the hepatitis B core antigen revealed evidence of hepatitis B virus infection in three. None of the three, however, developed overt clinical hepatitis or the chronic HBsAg carrier state. These data suggest that the immunologic defects seen in the Wiskott-Aldrich syndrome permit adequate immune responses to the hepatitis B virus and do not predispose to the chronic HBsAg carrier state."} {"id": "PMID:1255312", "title": "Provocative tests for growth hormone release.", "content": "Subnormal growth hormone responses to both insulin-induced hypoglycemia and arginine infusion (peak response less than or equal to 5 ng/ml) were found in five male subjects (aged 10 to 14 years) with short stature but with normal interval growth rates and normal bone ages (in 4 cases). They demonstrated one or more normal GH responses to subsequent provocation by glucagon stimulation, tolbutamide-induced hypoglycemia, and repeat insulin and arginine testing following pretreatment with sex steroids. Two subjects had received exogensou GH therapy for six months prior to the subsequent assessment; each one failed to demonstrate the growth response characteristic of GH deficiency. These studies indicate the need for multiple provocative human GH testing to exclude children whose growth would not be enhanced by GH therapy despite a subnormal response to provocative tests with insulin and arginine.", "contents": "Provocative tests for growth hormone release. Subnormal growth hormone responses to both insulin-induced hypoglycemia and arginine infusion (peak response less than or equal to 5 ng/ml) were found in five male subjects (aged 10 to 14 years) with short stature but with normal interval growth rates and normal bone ages (in 4 cases). They demonstrated one or more normal GH responses to subsequent provocation by glucagon stimulation, tolbutamide-induced hypoglycemia, and repeat insulin and arginine testing following pretreatment with sex steroids. Two subjects had received exogensou GH therapy for six months prior to the subsequent assessment; each one failed to demonstrate the growth response characteristic of GH deficiency. These studies indicate the need for multiple provocative human GH testing to exclude children whose growth would not be enhanced by GH therapy despite a subnormal response to provocative tests with insulin and arginine."} {"id": "PMID:1255313", "title": "Constrictive pericarditis with dwarfism in two siblings (mulibrey nanism).", "content": "Two siblings with marked dwarfism, now 11 and 19 years of age, have been followed from infancy. The girl had frequent episodes of pneumonitis and presented at age 4 years with hepatic enlargement and ascites which proved to be due to constrictive pericarditis. The boy presented with growth failure and pseudohydrocephalus. He had fibrous dysplasia of the tibia and a pathologic fracture; acute hepatic congestion followed physical activity at age 13 years and led to the diagnosis of constrictive pericarditis. Muscle function was normal, there was no evidence for a primary liver disorder, and mental development was normal so that the coined word \"mulibray\" seemed inappropriate. Pericardiectomy produced only partial improvement; both patients have hepatic enlargement and continue to need diuretics. A third patient with dwarfism, frequent respiratory infections, and pericardial calcification has certain features of the syndrome.", "contents": "Constrictive pericarditis with dwarfism in two siblings (mulibrey nanism). Two siblings with marked dwarfism, now 11 and 19 years of age, have been followed from infancy. The girl had frequent episodes of pneumonitis and presented at age 4 years with hepatic enlargement and ascites which proved to be due to constrictive pericarditis. The boy presented with growth failure and pseudohydrocephalus. He had fibrous dysplasia of the tibia and a pathologic fracture; acute hepatic congestion followed physical activity at age 13 years and led to the diagnosis of constrictive pericarditis. Muscle function was normal, there was no evidence for a primary liver disorder, and mental development was normal so that the coined word \"mulibray\" seemed inappropriate. Pericardiectomy produced only partial improvement; both patients have hepatic enlargement and continue to need diuretics. A third patient with dwarfism, frequent respiratory infections, and pericardial calcification has certain features of the syndrome."} {"id": "PMID:1255314", "title": "The acro-osteolysis syndrome: Morphologic and biochemical studies.", "content": "The acro-osteolysis syndrome consists of dissolution of terminal phalanges of the hands and feet, dolichocephaly with multiple wormian bones, delayed closure of cranial sutures, absence of frontal sinuses, a prominent occipital ridge, skeletal demineralization, vertebral and extremity fractures, joint laxity, and coarse hair. Studies of bone morphology reveal diminished bone density and bone formation. Osteoblasts have widely dilated smooth endoplasmic reticulum. It is postulated that an abnormality of a structural protein is the pathogenic basis of this disease.", "contents": "The acro-osteolysis syndrome: Morphologic and biochemical studies. The acro-osteolysis syndrome consists of dissolution of terminal phalanges of the hands and feet, dolichocephaly with multiple wormian bones, delayed closure of cranial sutures, absence of frontal sinuses, a prominent occipital ridge, skeletal demineralization, vertebral and extremity fractures, joint laxity, and coarse hair. Studies of bone morphology reveal diminished bone density and bone formation. Osteoblasts have widely dilated smooth endoplasmic reticulum. It is postulated that an abnormality of a structural protein is the pathogenic basis of this disease."} {"id": "PMID:1255315", "title": "Leukocyte glutathione peroxidase deficiency in a male patient with chronic granulomatous disease.", "content": "A male child with chronic granulomatous disease is described in whom glutathione peroxidase deficiency of leukocytes was identified. Stability and activity of G-6-PD and activity of NADPH oxidase were normal. The leukocytes of the parents showed intermediate activities of glutathione peroxidase, suggesting the possibility of autosomal recessive inheritance.", "contents": "Leukocyte glutathione peroxidase deficiency in a male patient with chronic granulomatous disease. A male child with chronic granulomatous disease is described in whom glutathione peroxidase deficiency of leukocytes was identified. Stability and activity of G-6-PD and activity of NADPH oxidase were normal. The leukocytes of the parents showed intermediate activities of glutathione peroxidase, suggesting the possibility of autosomal recessive inheritance."} {"id": "PMID:1255316", "title": "Joint contracture--common manifestation of childhood diabetes mellitus.", "content": "Sixty-five of 229 seven to eighteen-year-old campers with diabetes were found to have contractures of finger joints; in two thirds of affected children only the fifth finger was involved. Stiff resistance to passive finger manipulation and thickened adherent skin over the dorsa of the hands were additional features. Short stature was associated with involvement of more than one finger; the shortest youngsters also had contractures of large joints. Joint changes were independent of age, sex, age of onset of diabetes, and control of diabetes, but correlated with duration of the diabetes.", "contents": "Joint contracture--common manifestation of childhood diabetes mellitus. Sixty-five of 229 seven to eighteen-year-old campers with diabetes were found to have contractures of finger joints; in two thirds of affected children only the fifth finger was involved. Stiff resistance to passive finger manipulation and thickened adherent skin over the dorsa of the hands were additional features. Short stature was associated with involvement of more than one finger; the shortest youngsters also had contractures of large joints. Joint changes were independent of age, sex, age of onset of diabetes, and control of diabetes, but correlated with duration of the diabetes."} {"id": "PMID:1255321", "title": "Cerebellar hemorrhage in the premature infant.", "content": "Lesions of the central nervous system were reviewed in 144 premature neonates without anomalies or infections coming to autopsy from the Intermountain Regional Neonatal Intensive Care Unit. Twelve neonates were found to have had cerebellar hemorrhages. Eleven of the 12 with cerebellar hemorrhage also had germinal plate hemorrhages at postmortem examination. Some hemorrhages destroyed one or both cerebellar hemispheres. Three of 19 (16%) infants between 20 to 24 weeks' gestation, six of 26 (25%) infants between 26 to 28 weeks' gestation, two of 24 (8%) infants between 28 to 30 weeks' gestation, and one of 19 (5%) infants between 20 to 32 weeks' gestation had cerebellar hemorrhage. No premature neonate after 32 weeks' gestation had cerebellar hemorrhage. It is probable that trauma does not play a role in the pathogenesis of the cerebellar hemorrhage.", "contents": "Cerebellar hemorrhage in the premature infant. Lesions of the central nervous system were reviewed in 144 premature neonates without anomalies or infections coming to autopsy from the Intermountain Regional Neonatal Intensive Care Unit. Twelve neonates were found to have had cerebellar hemorrhages. Eleven of the 12 with cerebellar hemorrhage also had germinal plate hemorrhages at postmortem examination. Some hemorrhages destroyed one or both cerebellar hemispheres. Three of 19 (16%) infants between 20 to 24 weeks' gestation, six of 26 (25%) infants between 26 to 28 weeks' gestation, two of 24 (8%) infants between 28 to 30 weeks' gestation, and one of 19 (5%) infants between 20 to 32 weeks' gestation had cerebellar hemorrhage. No premature neonate after 32 weeks' gestation had cerebellar hemorrhage. It is probable that trauma does not play a role in the pathogenesis of the cerebellar hemorrhage."} {"id": "PMID:1255322", "title": "Variance in albumin loading in exchange transfusions.", "content": "To assess the rationale of albumin priming prior to exchange transfusions, 42 hyperbilirubinemic infants who required exchange transfusions were randomly assigned to one of two groups. Group I consisted of 15 infants who were given intravenously 1 gm/kg of salt-poor human serum albumin one hour before the exchanges. Group II, which consisted of 27 infants, received simple exchanges. No statistical differences were found in variations in reserve albumin-binding capacity, bilirubin, albumin, or red cell bilirubin at pre and one-hour post albumin infusion in the primed infants. The amount of bilirubin removed per kilogram is directly correlated to plasma bilirubin concentration (r=0.87). No significant difference in efficiency on bilirubin removal was seen between the two groups. Beneficial effects of albumin therapy was apparent only in those infants with low RABC as determined by the sephadex gel filtration technique.", "contents": "Variance in albumin loading in exchange transfusions. To assess the rationale of albumin priming prior to exchange transfusions, 42 hyperbilirubinemic infants who required exchange transfusions were randomly assigned to one of two groups. Group I consisted of 15 infants who were given intravenously 1 gm/kg of salt-poor human serum albumin one hour before the exchanges. Group II, which consisted of 27 infants, received simple exchanges. No statistical differences were found in variations in reserve albumin-binding capacity, bilirubin, albumin, or red cell bilirubin at pre and one-hour post albumin infusion in the primed infants. The amount of bilirubin removed per kilogram is directly correlated to plasma bilirubin concentration (r=0.87). No significant difference in efficiency on bilirubin removal was seen between the two groups. Beneficial effects of albumin therapy was apparent only in those infants with low RABC as determined by the sephadex gel filtration technique."} {"id": "PMID:1255323", "title": "Persistent fetal circulation: Newly recognized structural features.", "content": "Three infants died with pulmonary hypertension of unknown cause during the first three months of life. Their lungs were examined using quantitative morphologic techniques. In all three cases the intra-acinar pulmonary arteries were more muscular than normal, as shown both by an increase in thickness of the muscle coat in arteries which are normally muscular, and by extension of muscle into smaller and more peripheral intra-acinar arteries not normally muscular at this age. It is suggested that \"persistent pulmonary hypertension\" of the newborn infant is, in some infants, due to a structural abnormality of the pulmonary circulation which is present at birth.", "contents": "Persistent fetal circulation: Newly recognized structural features. Three infants died with pulmonary hypertension of unknown cause during the first three months of life. Their lungs were examined using quantitative morphologic techniques. In all three cases the intra-acinar pulmonary arteries were more muscular than normal, as shown both by an increase in thickness of the muscle coat in arteries which are normally muscular, and by extension of muscle into smaller and more peripheral intra-acinar arteries not normally muscular at this age. It is suggested that \"persistent pulmonary hypertension\" of the newborn infant is, in some infants, due to a structural abnormality of the pulmonary circulation which is present at birth."} {"id": "PMID:1255324", "title": "Neonatal hyperuricemia.", "content": "Serum concentrations and urinary excretion of uric acid were measured in ten normal newborn infants and in 13 patients with the idiopathic respiratory distress syndrome. In the normal infants, serum urate increased from a mean value of 6.0 mg/dl in cord blood to 7.0 mg/dl at 24 hours, followed by a decrease to 3.5 mg/dl over the next three days. The infants with IRDS had higher serum urate concentrations during the first three days of life, and the urinary excretion of uric acid over the period of 12 to 36 hours of age was also higher than in the normal infants. In both groups of neonates the correlation of maximal serum urate values with the urinary excretion was positive, which indicates that neonatal hyperuricemia is not due to renal retention but to increased production of uric acid. It is postulated that this overproduction results from increased nucleotide breakdown associated with perinatal hypoxia. Because of high serum and urinary uric acid concentrations, maintenance of adequate hydration and urinary flow as well as alkalinization of urine is recommended.", "contents": "Neonatal hyperuricemia. Serum concentrations and urinary excretion of uric acid were measured in ten normal newborn infants and in 13 patients with the idiopathic respiratory distress syndrome. In the normal infants, serum urate increased from a mean value of 6.0 mg/dl in cord blood to 7.0 mg/dl at 24 hours, followed by a decrease to 3.5 mg/dl over the next three days. The infants with IRDS had higher serum urate concentrations during the first three days of life, and the urinary excretion of uric acid over the period of 12 to 36 hours of age was also higher than in the normal infants. In both groups of neonates the correlation of maximal serum urate values with the urinary excretion was positive, which indicates that neonatal hyperuricemia is not due to renal retention but to increased production of uric acid. It is postulated that this overproduction results from increased nucleotide breakdown associated with perinatal hypoxia. Because of high serum and urinary uric acid concentrations, maintenance of adequate hydration and urinary flow as well as alkalinization of urine is recommended."} {"id": "PMID:1255325", "title": "The relationship of serum alkaline phosphatase concentrations to sex maturity ratings in adolescents.", "content": "The relationship of serum alkaline phosphatase concentrations to sex maturity ratings, age sex, and race was studied in healthy prepubertal and adolescent patients. Previous data concerning SAP concentrations in adolescents have been age related and do not give primary consideration to biologic growth during adolescence. The highest mean concentrations for girls occurred at SMR 2 and for boys at SMR 3, coinciding in each instance with peak height velocity and thus correlating with presumed maximum osteoblastic activity during growth. With increasing SMR or age, the SAP levels in both sexes decreased markedly. Black boys had higher SAP concnetrations than white boys at SMRs 2, 3 and 4, whereas black girls had higher values than white girls only at SMR 4. This study demonstrates the value of correlating the enzyme activity with sex maturity ratings rather than with chronologic age.", "contents": "The relationship of serum alkaline phosphatase concentrations to sex maturity ratings in adolescents. The relationship of serum alkaline phosphatase concentrations to sex maturity ratings, age sex, and race was studied in healthy prepubertal and adolescent patients. Previous data concerning SAP concentrations in adolescents have been age related and do not give primary consideration to biologic growth during adolescence. The highest mean concentrations for girls occurred at SMR 2 and for boys at SMR 3, coinciding in each instance with peak height velocity and thus correlating with presumed maximum osteoblastic activity during growth. With increasing SMR or age, the SAP levels in both sexes decreased markedly. Black boys had higher SAP concnetrations than white boys at SMRs 2, 3 and 4, whereas black girls had higher values than white girls only at SMR 4. This study demonstrates the value of correlating the enzyme activity with sex maturity ratings rather than with chronologic age."} {"id": "PMID:1255326", "title": "Neonatal narcotic abstinence: Effects of pharmacotherapeutic agents and maternal drug usage on nutritive sucking behavior.", "content": "An uncoordinated and ineffectual sucking reflex is a major manifestation of neonatal narcotic abstinence and may have important consequences for the infant's subsequent well being. Measures of nutritive sucking were used to monitor the severity of neonatal narcotic abstinence in a series of infants born to narcotic-dependent mothers who were either attending the methadone clinic or else were \"street addicts.\" In all these infants, sucking measures were significantly reduced relative to normal control subjects. Furthermore, the sucking behavior of infants born to mothers attending the methadone clinic was significantly more depressed than that of infants born to street addicts. In regard to the salutary effects of pharmacotherapy for neonatal narcotic abstinence, infants treated with paregoric approached normal control levels and showed significantly better sucking than those treated with phenobarbital or diazepam. The latter drug practically eliminated all spontaneous nutritive sucking behavior.", "contents": "Neonatal narcotic abstinence: Effects of pharmacotherapeutic agents and maternal drug usage on nutritive sucking behavior. An uncoordinated and ineffectual sucking reflex is a major manifestation of neonatal narcotic abstinence and may have important consequences for the infant's subsequent well being. Measures of nutritive sucking were used to monitor the severity of neonatal narcotic abstinence in a series of infants born to narcotic-dependent mothers who were either attending the methadone clinic or else were \"street addicts.\" In all these infants, sucking measures were significantly reduced relative to normal control subjects. Furthermore, the sucking behavior of infants born to mothers attending the methadone clinic was significantly more depressed than that of infants born to street addicts. In regard to the salutary effects of pharmacotherapy for neonatal narcotic abstinence, infants treated with paregoric approached normal control levels and showed significantly better sucking than those treated with phenobarbital or diazepam. The latter drug practically eliminated all spontaneous nutritive sucking behavior."} {"id": "PMID:1255327", "title": "A study of factors that influence the severity of neonatal narcotic withdrawal.", "content": "A prospective study of 196 drug-addicted mothers and their infants was conducted to determine the maternal, fetal, or environmental factors that may affect the severity of narcotic withdrawal in the infants. The severity of neonatal withdrawal did not correlate with the infant's gestational age, sex, race, or Apgar score, not to maternal age, parity, duration of heroin intake, or the level of morphine measured in the infant's urine or blood. Reduction in the amount of illumination and noise in a study nursery also did not lower the incidence of severe withdrawal in the infants. There was, however, significant correlation between the severity of withdrawal in the infant and the maternal methadone dose (p less than 0.025). It is therefore recommended that mothers on methadone treatment be put on a low dose of the drug (less than 20 mg/day) as soon as is safely possible to prevent serious withdrawal in her infant.", "contents": "A study of factors that influence the severity of neonatal narcotic withdrawal. A prospective study of 196 drug-addicted mothers and their infants was conducted to determine the maternal, fetal, or environmental factors that may affect the severity of narcotic withdrawal in the infants. The severity of neonatal withdrawal did not correlate with the infant's gestational age, sex, race, or Apgar score, not to maternal age, parity, duration of heroin intake, or the level of morphine measured in the infant's urine or blood. Reduction in the amount of illumination and noise in a study nursery also did not lower the incidence of severe withdrawal in the infants. There was, however, significant correlation between the severity of withdrawal in the infant and the maternal methadone dose (p less than 0.025). It is therefore recommended that mothers on methadone treatment be put on a low dose of the drug (less than 20 mg/day) as soon as is safely possible to prevent serious withdrawal in her infant."} {"id": "PMID:1255328", "title": "Treatment of skin irritation around enterostomies with cholestyramine ointment.", "content": "Eight patients with inflammation of the skin about the cutaneous stoma responded to local application of a 20% cholestyramine ointment in a short period of time. Two children treated with the hydrophilic base (Aquaphor) alone did not respond to treatment. The ileal bile acid patterns of two children with ileostomies were found to be different from that of the control group. Ileostomy patients had a higher concentration for total bile acids and a higher percentage of free bile acids.", "contents": "Treatment of skin irritation around enterostomies with cholestyramine ointment. Eight patients with inflammation of the skin about the cutaneous stoma responded to local application of a 20% cholestyramine ointment in a short period of time. Two children treated with the hydrophilic base (Aquaphor) alone did not respond to treatment. The ileal bile acid patterns of two children with ileostomies were found to be different from that of the control group. Ileostomy patients had a higher concentration for total bile acids and a higher percentage of free bile acids."} {"id": "PMID:1255329", "title": "A six-year controlled trial of prevention of children's behavior disorders.", "content": "Preschool interviews between a clinician and mothers were studied to determine their influence upon the behavioral patterns and learning abilities of the mother's children. After six years, 124 children of this experimental group were compared with 122 control children; the results indicated that a significant number of experimental children had fewer fears, sleep disorders, eating problems, loud modes of speech, and aggression toward others and fewer of the girls distorted events to their advantage or demanded their parents to share in joint play. A larger proportion of the experimental children had positive feelings, and to a lesser degree negative feelings, toward their mothers, but a greater number were late for school, with more of the boys being excitable and hard to control. The greater benefits, which were more apparent in the girls than in the boys, were consistent with an effectiveness of more firmly expressed views about the girls, whereas the confidence of the boys' mothers may well have been affected by too cautious an approach to discipline problems. The interviews probably had no influence on the children's learning capacities.", "contents": "A six-year controlled trial of prevention of children's behavior disorders. Preschool interviews between a clinician and mothers were studied to determine their influence upon the behavioral patterns and learning abilities of the mother's children. After six years, 124 children of this experimental group were compared with 122 control children; the results indicated that a significant number of experimental children had fewer fears, sleep disorders, eating problems, loud modes of speech, and aggression toward others and fewer of the girls distorted events to their advantage or demanded their parents to share in joint play. A larger proportion of the experimental children had positive feelings, and to a lesser degree negative feelings, toward their mothers, but a greater number were late for school, with more of the boys being excitable and hard to control. The greater benefits, which were more apparent in the girls than in the boys, were consistent with an effectiveness of more firmly expressed views about the girls, whereas the confidence of the boys' mothers may well have been affected by too cautious an approach to discipline problems. The interviews probably had no influence on the children's learning capacities."} {"id": "PMID:1255330", "title": "An attempt to identify frequency of use of technical skills and procedures by the primary care physician.", "content": "Some technical skills required and learned during residency training are not often used in primary care. Pediatricians who practice primary care in rural settings for smaller communities) tend to perform a greater variety of procedures than those who practice in urban settings. Family practitioners report that they perform more of these procedures than either rural or urban practicing pediatricians. Training programs should define the skills and procedures which residents must learn to perform and should differentiate between those needed during the training period and those which will be used in primary care practice.", "contents": "An attempt to identify frequency of use of technical skills and procedures by the primary care physician. Some technical skills required and learned during residency training are not often used in primary care. Pediatricians who practice primary care in rural settings for smaller communities) tend to perform a greater variety of procedures than those who practice in urban settings. Family practitioners report that they perform more of these procedures than either rural or urban practicing pediatricians. Training programs should define the skills and procedures which residents must learn to perform and should differentiate between those needed during the training period and those which will be used in primary care practice."} {"id": "PMID:1255351", "title": "Fasciola gigantica Cobbold 1856 in the snail.", "content": "Intramolluscan stages of Fasciola gigantica were followed experimentally in laboratory-reared Lymnaea natalensis, from the time of miracidial entry until the 85th day. Contrary to previous accounts, the miracidium was found to metamorphose directly into a first-generation redia during the first 4 days. About the 16th day, the redia migrated to the snail liver. Second-generation rediae gave rise to 3rd-generation rediae and/or cercariae by the 45th to 50th day. The release of cercariae from 3rd-generation rediae began around the 75th day, and from 4th-generation rediae after 85 days. All studies were conducted at ambient temperatures in the laboratory at Makerere University, Kampala, Uganda, in 1968-71.", "contents": "Fasciola gigantica Cobbold 1856 in the snail. Intramolluscan stages of Fasciola gigantica were followed experimentally in laboratory-reared Lymnaea natalensis, from the time of miracidial entry until the 85th day. Contrary to previous accounts, the miracidium was found to metamorphose directly into a first-generation redia during the first 4 days. About the 16th day, the redia migrated to the snail liver. Second-generation rediae gave rise to 3rd-generation rediae and/or cercariae by the 45th to 50th day. The release of cercariae from 3rd-generation rediae began around the 75th day, and from 4th-generation rediae after 85 days. All studies were conducted at ambient temperatures in the laboratory at Makerere University, Kampala, Uganda, in 1968-71."} {"id": "PMID:1255353", "title": "Pilum pilum gen. et sp. n. (Acanthocephala: Echinorhynchidae) from freshwater fishes of the southeastern United States.", "content": "Pilum pilum gen. et sp. n. is described from the warmouth, Lepomis gulosus (Cuvier); brown bullhead, Ictalurus nebulosus (Lesueur); yellow bullhead, I. natalis (Lesueur); redbreast sunfish, L. auritus (Linnaeus); bluegill, L. macrochirus Rafinesque; spotted sunfish, L. punctatus (Valenciennes); and redfin pickerel, Esox americanus (Gmelin), from the Alabama River Drainage, brown bullhead from the Mobile Bay Drainage in Alabama, and pirate perch, Aphredoderus sayanus Gilliams, from an Atlantic Coast drainage in Georgia. The new genus most closely resembles the genus Acanthocephalus; it differs from this genus in having a distinctive pear-shaped proboscis, a long neck, and hooks which abruptly differ in size.", "contents": "Pilum pilum gen. et sp. n. (Acanthocephala: Echinorhynchidae) from freshwater fishes of the southeastern United States. Pilum pilum gen. et sp. n. is described from the warmouth, Lepomis gulosus (Cuvier); brown bullhead, Ictalurus nebulosus (Lesueur); yellow bullhead, I. natalis (Lesueur); redbreast sunfish, L. auritus (Linnaeus); bluegill, L. macrochirus Rafinesque; spotted sunfish, L. punctatus (Valenciennes); and redfin pickerel, Esox americanus (Gmelin), from the Alabama River Drainage, brown bullhead from the Mobile Bay Drainage in Alabama, and pirate perch, Aphredoderus sayanus Gilliams, from an Atlantic Coast drainage in Georgia. The new genus most closely resembles the genus Acanthocephalus; it differs from this genus in having a distinctive pear-shaped proboscis, a long neck, and hooks which abruptly differ in size."} {"id": "PMID:1255354", "title": "Community ecology of helminth parasitism in an insular passerine avifauna.", "content": "Three hundred and thirty specimens of 7 species of passerine birds from South Bass Island, Ottawa County, Ohio, were examined for helminth parasites. The total number of helminth specimens collected was 4,333. Forty-one helminth taxa were identified. Ten species of helminths were identified as having foci of infection on the island. An index of association for these 10 species is presented. The low association revealed between helminth species utilizing common species of intermediate hosts indicated that a single intermediate host specimen is likely to harbor infective stages of only one species of parasitic helminth. An index of similarity is presented to express the species importance relationships of the helminth faunas of the 7 species of birds: red-winged blackbirds (Agelaius phoeniceus), blue jays (Cyanocitta cristata), brown-headed cowbirds (Molothrus ater), common grackles (Quiscalus quiscula), house sparrows (Passer domesticus), starlings (Sturnus vulgaris), and robins (Turdus migratorius). The results reveal that competition between these avian species for invertebrate food resources helps to maximize the transmission of those helminth populations which utilize these same invertebrates as intermediate hosts. The aggregation of birds into mixed feeding flocks insures a heavy loading of the feeding grounds with agents infective for the invertebrate populations.", "contents": "Community ecology of helminth parasitism in an insular passerine avifauna. Three hundred and thirty specimens of 7 species of passerine birds from South Bass Island, Ottawa County, Ohio, were examined for helminth parasites. The total number of helminth specimens collected was 4,333. Forty-one helminth taxa were identified. Ten species of helminths were identified as having foci of infection on the island. An index of association for these 10 species is presented. The low association revealed between helminth species utilizing common species of intermediate hosts indicated that a single intermediate host specimen is likely to harbor infective stages of only one species of parasitic helminth. An index of similarity is presented to express the species importance relationships of the helminth faunas of the 7 species of birds: red-winged blackbirds (Agelaius phoeniceus), blue jays (Cyanocitta cristata), brown-headed cowbirds (Molothrus ater), common grackles (Quiscalus quiscula), house sparrows (Passer domesticus), starlings (Sturnus vulgaris), and robins (Turdus migratorius). The results reveal that competition between these avian species for invertebrate food resources helps to maximize the transmission of those helminth populations which utilize these same invertebrates as intermediate hosts. The aggregation of birds into mixed feeding flocks insures a heavy loading of the feeding grounds with agents infective for the invertebrate populations."} {"id": "PMID:1255356", "title": "Tinaminyssus juxtamelloi sp. n. (Acari: Dermanyssidae; Rhinonyssinae) from the nasal passages of the band-tailed pigeon, Columba fasciata, in New Mexico.", "content": "Tinaminyssus juxtamelloi sp. n. is described from the nasal passages of Columba fasciata in New Mexico. The new species is most similar to Tinaminyssus melloi (Castro) 1948 and T. turturi (Fain) 1962, but differs in (1) possessing only 5 pairs of ventral opisthosomal setae, (2) presence of 3 pairs of enlarged setae on the dorsal opisthosoma at the posterolateral margin of the podosomal plate (1 pair) and at the lateral margins of the opisthosomal plate (2 pairs), (3) elongate shape and larger size of the poststigmatic plates, and (4) chaetotaxy and solenidiotaxy of the legs, especially tarsus I with a cluster of 4 solenida and 1 club-shaped solenidion on the apex of the dorsum. The relationships of this with allied species of the genus Tinaminyssus from columbiform birds are briefly discussed.", "contents": "Tinaminyssus juxtamelloi sp. n. (Acari: Dermanyssidae; Rhinonyssinae) from the nasal passages of the band-tailed pigeon, Columba fasciata, in New Mexico. Tinaminyssus juxtamelloi sp. n. is described from the nasal passages of Columba fasciata in New Mexico. The new species is most similar to Tinaminyssus melloi (Castro) 1948 and T. turturi (Fain) 1962, but differs in (1) possessing only 5 pairs of ventral opisthosomal setae, (2) presence of 3 pairs of enlarged setae on the dorsal opisthosoma at the posterolateral margin of the podosomal plate (1 pair) and at the lateral margins of the opisthosomal plate (2 pairs), (3) elongate shape and larger size of the poststigmatic plates, and (4) chaetotaxy and solenidiotaxy of the legs, especially tarsus I with a cluster of 4 solenida and 1 club-shaped solenidion on the apex of the dorsum. The relationships of this with allied species of the genus Tinaminyssus from columbiform birds are briefly discussed."} {"id": "PMID:1255357", "title": "Dermacarus jonesi sp. n. (acari: Labidophorinae: Glycyphagidae) from Peromyscus maniculatus from western North America.", "content": "A new species of labidophorine hypopus, Dermacarus jonesi, is described from Peromyscus maniculatus from Washington, USA, and British Columbia, Canada. A single individual was also found on Sorex sp. from California.", "contents": "Dermacarus jonesi sp. n. (acari: Labidophorinae: Glycyphagidae) from Peromyscus maniculatus from western North America. A new species of labidophorine hypopus, Dermacarus jonesi, is described from Peromyscus maniculatus from Washington, USA, and British Columbia, Canada. A single individual was also found on Sorex sp. from California."} {"id": "PMID:1255367", "title": "Immunity to monomorphic Trypanosoma brucei: humoral response.", "content": "Trypanosome-agglutinating antibodies, predominantly of the IgM class, are formed in T. brucei-infected rats cured with Berenil (diminazene). The duration of Berenil prophylaxis following administration of a minimum curative dose is approximately 28 days. Rechallenge of drug-cured animals with homologous organisms results in the production of IgG, indicating an apparent absence of interference under these conditions with B-cell, T-cell cooperativity.", "contents": "Immunity to monomorphic Trypanosoma brucei: humoral response. Trypanosome-agglutinating antibodies, predominantly of the IgM class, are formed in T. brucei-infected rats cured with Berenil (diminazene). The duration of Berenil prophylaxis following administration of a minimum curative dose is approximately 28 days. Rechallenge of drug-cured animals with homologous organisms results in the production of IgG, indicating an apparent absence of interference under these conditions with B-cell, T-cell cooperativity."} {"id": "PMID:1255380", "title": "Development of the large American liver fluke, Fascioloides magna, in white-tailed deer, cattle, and sheep.", "content": "The comparative development of Fascioloides magna in white-tailed deer, cattle and sheep has been studied. Flukes were recovered from 72% of 32 deer administered 40 to 500 metacercariae, from 82% of 11 cattle administered 10 to 500 metacercariae, and from 53% of 15 sheep administered 8 to 200 metacercariae. The percentage recovery of the flukes administered as metacercariae was 4.1% of 6,130 in deer, 5.7% of 2,510 in cattle, and 4.7% of 1,213 in sheep. Flukes were recovered only from livers of infected deer, while in cattle, 1 fluke was also found in the lungs of each of 2 animals. In sheep, all but 10 flukes were recovered from the livers; 6 were found in the lungs and 4 in the abdominal cavities. The black iron porphyrin pigment associated with F. magna infection was found to be most widespread in cattle and sheep, but was also a pathognomonic feature in deer. Growth of the fluke was similar in all 3 host species tested, but eggs were passed only from deer, the normal definitive host. In cattle, the eggs were retained in the liver, and F. magna was lethal to sheep before its own maturity was attained. In cattle and deer, flukes matured approximately 7 months after exposure, but immature migrating flukes were found 12 months after infection and apparently can remain in this retarded state for an undetermined period of time.", "contents": "Development of the large American liver fluke, Fascioloides magna, in white-tailed deer, cattle, and sheep. The comparative development of Fascioloides magna in white-tailed deer, cattle and sheep has been studied. Flukes were recovered from 72% of 32 deer administered 40 to 500 metacercariae, from 82% of 11 cattle administered 10 to 500 metacercariae, and from 53% of 15 sheep administered 8 to 200 metacercariae. The percentage recovery of the flukes administered as metacercariae was 4.1% of 6,130 in deer, 5.7% of 2,510 in cattle, and 4.7% of 1,213 in sheep. Flukes were recovered only from livers of infected deer, while in cattle, 1 fluke was also found in the lungs of each of 2 animals. In sheep, all but 10 flukes were recovered from the livers; 6 were found in the lungs and 4 in the abdominal cavities. The black iron porphyrin pigment associated with F. magna infection was found to be most widespread in cattle and sheep, but was also a pathognomonic feature in deer. Growth of the fluke was similar in all 3 host species tested, but eggs were passed only from deer, the normal definitive host. In cattle, the eggs were retained in the liver, and F. magna was lethal to sheep before its own maturity was attained. In cattle and deer, flukes matured approximately 7 months after exposure, but immature migrating flukes were found 12 months after infection and apparently can remain in this retarded state for an undetermined period of time."} {"id": "PMID:1255381", "title": "Ultrastructure of Pharyngostomoides procyonis Harkema 1942 (Diplostomatidae). I. Observations on the male reproductive system.", "content": "Spermatogonia, nutritive cells, and developmental stages of spermatids were observed with the electron microscope. Spermatogonia are near the surface of the testis and contain large nuclei and comparatively little cytoplasm. Nutritive or supporting cells are associated with the spermatogonia. Early spermatids are characterized by a circle of mitochondria around the nucleus. Late spermatids have 2 parallel free flagella separated by a cytoplasmic process, and a nucleus containing electron-dense strands of chromatin arranged in coils or concentric layers. Mature sperm have 2 flagella enclosed by cytoplasm. Their nuclei contain dense, fibrillar chromatin. A microtubule-organizing center (MTOC) found between basal bodies of spermatids is described. Descriptions are presented of the seminal reservoir, seminal vesicle, and the sperm found in those organs.", "contents": "Ultrastructure of Pharyngostomoides procyonis Harkema 1942 (Diplostomatidae). I. Observations on the male reproductive system. Spermatogonia, nutritive cells, and developmental stages of spermatids were observed with the electron microscope. Spermatogonia are near the surface of the testis and contain large nuclei and comparatively little cytoplasm. Nutritive or supporting cells are associated with the spermatogonia. Early spermatids are characterized by a circle of mitochondria around the nucleus. Late spermatids have 2 parallel free flagella separated by a cytoplasmic process, and a nucleus containing electron-dense strands of chromatin arranged in coils or concentric layers. Mature sperm have 2 flagella enclosed by cytoplasm. Their nuclei contain dense, fibrillar chromatin. A microtubule-organizing center (MTOC) found between basal bodies of spermatids is described. Descriptions are presented of the seminal reservoir, seminal vesicle, and the sperm found in those organs."} {"id": "PMID:1255383", "title": "Studies on resistance in snails. 3. Tissue reactions to Echinostoma lindoense sporocysts in sensitized and resensitized Biomphalaria glabrata.", "content": "The resistance of Biomphalaria glabrata snails that have been sensitized by various levels of irradiated or nonirradiated Echinostoma lindoense miracidia increased after a second challenge infection with nonirradiated miracidia of the same species. This was demonstrated by increased suppression of migrating capacity of invading sporocysts, an accelerated host tissue reaction, and a greater tendency of snail amebocytes to flatten while attacking the parasite. Three methods of elimination of invading sporocysts were observed: (1) encapsulation by amebocytes followed by destruction of the sporocysts; (2) expulsion of the sporocyst through the host epithelium after its encapsulation in the subepithelial tissues; (3) blockade of the parasite's entry into subepithelial tissues by a localized amebocyte aggregation. The basic mechanism of host snail response to a single or a repeated challenge infection appears to be similar, though an anamnestic reaction is evident in the accelerated response following a second challenge exposure.", "contents": "Studies on resistance in snails. 3. Tissue reactions to Echinostoma lindoense sporocysts in sensitized and resensitized Biomphalaria glabrata. The resistance of Biomphalaria glabrata snails that have been sensitized by various levels of irradiated or nonirradiated Echinostoma lindoense miracidia increased after a second challenge infection with nonirradiated miracidia of the same species. This was demonstrated by increased suppression of migrating capacity of invading sporocysts, an accelerated host tissue reaction, and a greater tendency of snail amebocytes to flatten while attacking the parasite. Three methods of elimination of invading sporocysts were observed: (1) encapsulation by amebocytes followed by destruction of the sporocysts; (2) expulsion of the sporocyst through the host epithelium after its encapsulation in the subepithelial tissues; (3) blockade of the parasite's entry into subepithelial tissues by a localized amebocyte aggregation. The basic mechanism of host snail response to a single or a repeated challenge infection appears to be similar, though an anamnestic reaction is evident in the accelerated response following a second challenge exposure."} {"id": "PMID:1255384", "title": "Corrigia Obscura Sp. N. (Trematoda: Dicrocoeliidae) from the North American black duck.", "content": "Corrigia obscura sp. n. was found in the pancreatic ducts of a black duck, Anas rubripes. This is the first record of the genus Corrigia from an anseriform bird and from North America. Corrigia obscura differs from other Corrigia spp. by having a greater relative forebody length and greater relative body width. Noticeable hyperplasia and sloughing of the wall of the pancreatic ducts were associated with this infection.", "contents": "Corrigia Obscura Sp. N. (Trematoda: Dicrocoeliidae) from the North American black duck. Corrigia obscura sp. n. was found in the pancreatic ducts of a black duck, Anas rubripes. This is the first record of the genus Corrigia from an anseriform bird and from North America. Corrigia obscura differs from other Corrigia spp. by having a greater relative forebody length and greater relative body width. Noticeable hyperplasia and sloughing of the wall of the pancreatic ducts were associated with this infection."} {"id": "PMID:1255386", "title": "Scanning electron microscopy of the integumental surfaces of Schistosoma haematobium.", "content": "The integumental surfaces of critical point dried S. haematobium were studied by scanning electron microscopy at 34 to 8,000 magnifications. There are marked differences between the surface structures of male and female as well as from one part of the same parasite to another. The surface of the male schistosome is moderately rough while that of the female is relatively smooth. SEM reveals certain basic features such as spines in the oral sucker and the acetabulum of both sexes which may facilitate rasping and/or attachment of the parasite for residence in the bloodstream of the definitive host. The lining of the gynecophoral canal is roughened by minute spines. The presence of a gynecophoral fold may enhance anchorage of the female in the grasp of the male. The significance of visualization of surface features by SEM as a means for differentiating species is not yet known.", "contents": "Scanning electron microscopy of the integumental surfaces of Schistosoma haematobium. The integumental surfaces of critical point dried S. haematobium were studied by scanning electron microscopy at 34 to 8,000 magnifications. There are marked differences between the surface structures of male and female as well as from one part of the same parasite to another. The surface of the male schistosome is moderately rough while that of the female is relatively smooth. SEM reveals certain basic features such as spines in the oral sucker and the acetabulum of both sexes which may facilitate rasping and/or attachment of the parasite for residence in the bloodstream of the definitive host. The lining of the gynecophoral canal is roughened by minute spines. The presence of a gynecophoral fold may enhance anchorage of the female in the grasp of the male. The significance of visualization of surface features by SEM as a means for differentiating species is not yet known."} {"id": "PMID:1255387", "title": "Some trypanorhynch cestodes from Hawaiian fishes, with descriptions of four new species.", "content": "Examination of teleost and elasmobranch fishes for cestodes from the Pacific Ocean off the Hawaiian Islands resulted in the recovery of 7 species of trypanorhynchs, 4 of which are new. The new species are Pseudogrillotia basipunctata, Pterobothrium hawaiiensis, Prochristianella micracantha, and Nybelinia basimegacantha. Tentacularia coryphaena Bosc 1797, Dasyrhynchus giganteus (Diesing 1859), and Parachristianella monomegacantha Kruse 1959 represent new host and distribution records. The family Pseudogrillotidae Dollfus 1969 is emended.", "contents": "Some trypanorhynch cestodes from Hawaiian fishes, with descriptions of four new species. Examination of teleost and elasmobranch fishes for cestodes from the Pacific Ocean off the Hawaiian Islands resulted in the recovery of 7 species of trypanorhynchs, 4 of which are new. The new species are Pseudogrillotia basipunctata, Pterobothrium hawaiiensis, Prochristianella micracantha, and Nybelinia basimegacantha. Tentacularia coryphaena Bosc 1797, Dasyrhynchus giganteus (Diesing 1859), and Parachristianella monomegacantha Kruse 1959 represent new host and distribution records. The family Pseudogrillotidae Dollfus 1969 is emended."} {"id": "PMID:1255388", "title": "Adsorption of bile salts by the cestodes, Hymenolepis diminuta and H. microstoma.", "content": "The accumulation of purified sodium taurocholate (NaTC) and sodium glycocholate (NaGC) by Hymenolepis diminuta and Hymenolepis microstoma (Cestoda: Cyclophyllidea) was determined using radioactive bile salts. H. diminuta reached equilibrium levels of approximately 120 nmoles NaTC/g dry wt and 300 nmoles NaGC/g dry wt. Presentation of the bile salts in mixed micelles with 0.35 mM oleic acid did not alter these values. With H. microstoma, the maxima were 195 nmoles NaTC/g dry wt and 614 nmoles NaCG/g dry wt. These values were similarly unaffected by the addition of 0.35 mM oleic acid to the micelles. Equilibrium values of this magnitude, in media containing as much as 25 or 30 mM bile salt, and the maintenance of this level during incubations of 15 to 60 min eliminated the possibility that the accumulation was by diffusion or by any form of mediated transport into the worm. The accumulation on NaTC by H. diminuta was [Na+] independent, and insensitive to ouabain, DNP, and high [K+]. These observations, the maintenance of different levels of NaTC and NaGC, and the failure of the 2 bile salts to compete indicated that there was no active excretion mechanism operating in a fashion similar to the active transport of bile salts in the vertebrate small intestine. It was concluded that the accumulation of NaTC by H. diminuta was actually adsorption to the tegument. Comparable, although more limited, experiments extended this conclusion to the accumulation of NaGC by H. diminuta and of NaTC and NaGC by H. microstoma. It is suggested that bile salt monomers, rather than intact micelles, adsorb to specific loci on the tegument.", "contents": "Adsorption of bile salts by the cestodes, Hymenolepis diminuta and H. microstoma. The accumulation of purified sodium taurocholate (NaTC) and sodium glycocholate (NaGC) by Hymenolepis diminuta and Hymenolepis microstoma (Cestoda: Cyclophyllidea) was determined using radioactive bile salts. H. diminuta reached equilibrium levels of approximately 120 nmoles NaTC/g dry wt and 300 nmoles NaGC/g dry wt. Presentation of the bile salts in mixed micelles with 0.35 mM oleic acid did not alter these values. With H. microstoma, the maxima were 195 nmoles NaTC/g dry wt and 614 nmoles NaCG/g dry wt. These values were similarly unaffected by the addition of 0.35 mM oleic acid to the micelles. Equilibrium values of this magnitude, in media containing as much as 25 or 30 mM bile salt, and the maintenance of this level during incubations of 15 to 60 min eliminated the possibility that the accumulation was by diffusion or by any form of mediated transport into the worm. The accumulation on NaTC by H. diminuta was [Na+] independent, and insensitive to ouabain, DNP, and high [K+]. These observations, the maintenance of different levels of NaTC and NaGC, and the failure of the 2 bile salts to compete indicated that there was no active excretion mechanism operating in a fashion similar to the active transport of bile salts in the vertebrate small intestine. It was concluded that the accumulation of NaTC by H. diminuta was actually adsorption to the tegument. Comparable, although more limited, experiments extended this conclusion to the accumulation of NaGC by H. diminuta and of NaTC and NaGC by H. microstoma. It is suggested that bile salt monomers, rather than intact micelles, adsorb to specific loci on the tegument."} {"id": "PMID:1255389", "title": "Effect of bile salts on the absorption of glucose and oleic acid by the cestodes, Hymenolepis diminuta and H. microstoma.", "content": "The uptake of 2 mM 14C-glucose by H. diminuta during 1-min incubations was inhibited by addition of 10 mM sodium taurocholate (NaTC) to the incubation media. Preincubation in 10 mM NaTC for 30 min did not increase the inhibition, suggesting that the inhibition was competitive. This was confirmed with a standard Lineweaver-Burk experiment. Addition of 0.35 mM oleic acid to the NaTC micelles did not alter the level of inhibition. Sodium glycocholate (NaGC) did not inhibit the uptake of glucose by H. diminuta. The uptake of glucose by H. microstoma was also inhibited by NaTC, and was not affected by NaGC. H. diminuta absorbed 3.62 mumoles of oleic acid/g dry wt during 15-min incubations in mixed micelles of 10 mM NaTC and 0.35 mM oleic acid. The total uptake was determined as the sum of the ethanol extractable and nonextractable 3H-oleic acid. In 15 mM NaTC, the uptake of oleic acid was reduced by 50%; at 30 mM NaTC the uptake of oleic acid decreased by half again. Substituting NaGC for NaTC, the greatest uptake of oleic acid, 2.63 mumoles/g dry wt, was from mixed micelles of 15 mM NaGC and 0.35 mM oleic acid. Lesser amounts of oleic acid were absorbed from mixed micelles at 5 or 30 mM NaGC. H. microstoma exhibited a similar pattern of oleic acid uptake from mixed micelles with NaTC and NaGC. At all bile salt concentrations tested, H. microstoma absorbed more oleic acid than H. diminuta and incorporated more oleic acid into the nonextractable pool. The possible roles of bile salts in the absorption of oleic acid as indicated by the results herein are discussed.", "contents": "Effect of bile salts on the absorption of glucose and oleic acid by the cestodes, Hymenolepis diminuta and H. microstoma. The uptake of 2 mM 14C-glucose by H. diminuta during 1-min incubations was inhibited by addition of 10 mM sodium taurocholate (NaTC) to the incubation media. Preincubation in 10 mM NaTC for 30 min did not increase the inhibition, suggesting that the inhibition was competitive. This was confirmed with a standard Lineweaver-Burk experiment. Addition of 0.35 mM oleic acid to the NaTC micelles did not alter the level of inhibition. Sodium glycocholate (NaGC) did not inhibit the uptake of glucose by H. diminuta. The uptake of glucose by H. microstoma was also inhibited by NaTC, and was not affected by NaGC. H. diminuta absorbed 3.62 mumoles of oleic acid/g dry wt during 15-min incubations in mixed micelles of 10 mM NaTC and 0.35 mM oleic acid. The total uptake was determined as the sum of the ethanol extractable and nonextractable 3H-oleic acid. In 15 mM NaTC, the uptake of oleic acid was reduced by 50%; at 30 mM NaTC the uptake of oleic acid decreased by half again. Substituting NaGC for NaTC, the greatest uptake of oleic acid, 2.63 mumoles/g dry wt, was from mixed micelles of 15 mM NaGC and 0.35 mM oleic acid. Lesser amounts of oleic acid were absorbed from mixed micelles at 5 or 30 mM NaGC. H. microstoma exhibited a similar pattern of oleic acid uptake from mixed micelles with NaTC and NaGC. At all bile salt concentrations tested, H. microstoma absorbed more oleic acid than H. diminuta and incorporated more oleic acid into the nonextractable pool. The possible roles of bile salts in the absorption of oleic acid as indicated by the results herein are discussed."} {"id": "PMID:1255391", "title": "Comparison of the uptake of vitamin B12 by Spirometra mansonoides and Hymenolepis diminuta and the functional groups of B12 analogs affecting uptake.", "content": "Uptake of 57Co-vitamin B12 (CN-Cbl) by spargana (larvae) of the pseudophyllidean tapeworm, Spirometra mansonoides, was affected by temperature, was saturable with respect to concentration of CN-Cbl in the medium, and was inhibited in the presence of several structural analogs of CN-Cbl. In uptake studies with various analogs it was found that chemical modifications which altered the benzimidazole moiety greatly reduced the ability of the worm to take up these analogs. Modifications in which the amide groups of the propionamide side chains were removed, resulting in carboxylic acid derivatives, showed greatly reduced transport properties. The C-13 epimer in which the e-proprionamide side chain is no longer on the benzimidazole side (lower) of the molecule but is inverted to a position on the upper side was freely taken up. The pharmacological implications of this last observation are discussed. Adult Hymenolepis diminuta did not take up CN-Cbl in vitro, which correlated with the finding that no CN-Cbl was detected in the worm by Ochromonas malhamensis assay.", "contents": "Comparison of the uptake of vitamin B12 by Spirometra mansonoides and Hymenolepis diminuta and the functional groups of B12 analogs affecting uptake. Uptake of 57Co-vitamin B12 (CN-Cbl) by spargana (larvae) of the pseudophyllidean tapeworm, Spirometra mansonoides, was affected by temperature, was saturable with respect to concentration of CN-Cbl in the medium, and was inhibited in the presence of several structural analogs of CN-Cbl. In uptake studies with various analogs it was found that chemical modifications which altered the benzimidazole moiety greatly reduced the ability of the worm to take up these analogs. Modifications in which the amide groups of the propionamide side chains were removed, resulting in carboxylic acid derivatives, showed greatly reduced transport properties. The C-13 epimer in which the e-proprionamide side chain is no longer on the benzimidazole side (lower) of the molecule but is inverted to a position on the upper side was freely taken up. The pharmacological implications of this last observation are discussed. Adult Hymenolepis diminuta did not take up CN-Cbl in vitro, which correlated with the finding that no CN-Cbl was detected in the worm by Ochromonas malhamensis assay."} {"id": "PMID:1255392", "title": "Effects of scoring norms on adolescent psychiatric patients' MMPI profiles.", "content": "Effects of employing standard adult and age-appropriate norms on the profile elevation, patterning and classification of adolescent patients' MMPI profiles were examined. More elevated and more often psychotic profiles were obtained with adult norms. Some sex differences were observed, but patient race was not an important source of profile variation.", "contents": "Effects of scoring norms on adolescent psychiatric patients' MMPI profiles. Effects of employing standard adult and age-appropriate norms on the profile elevation, patterning and classification of adolescent patients' MMPI profiles were examined. More elevated and more often psychotic profiles were obtained with adult norms. Some sex differences were observed, but patient race was not an important source of profile variation."} {"id": "PMID:1255393", "title": "Some properties of the ego-resiliency subtle scale of the MMPI.", "content": "The Ego Resiliency-Subtle (ER-S) scale was developed by Block (1965) as a social desirability free measure of the first factor of the MMPI. The purpose of the present experiments was to determine whether or not the 40-items comprising the ER-S scale remain neutral regarding social desirability and if the subject's score on the scale remains constant when taken out of the context of the other MMPI items; if so, the ER-S scale could be used as a screening device. Experiment I demonstrated that the items were not neutral regarding social desirability when taken out of context, but Experiment II indicated that this did not influence the responses subjects gave to the items. Because a memory factor may have been operating in Experiment II, a third experiment was conducted to minimize this factor resulting in a male-female vs. embedded-alone interaction and an order of presentation vs. embedded-alone interaction.", "contents": "Some properties of the ego-resiliency subtle scale of the MMPI. The Ego Resiliency-Subtle (ER-S) scale was developed by Block (1965) as a social desirability free measure of the first factor of the MMPI. The purpose of the present experiments was to determine whether or not the 40-items comprising the ER-S scale remain neutral regarding social desirability and if the subject's score on the scale remains constant when taken out of the context of the other MMPI items; if so, the ER-S scale could be used as a screening device. Experiment I demonstrated that the items were not neutral regarding social desirability when taken out of context, but Experiment II indicated that this did not influence the responses subjects gave to the items. Because a memory factor may have been operating in Experiment II, a third experiment was conducted to minimize this factor resulting in a male-female vs. embedded-alone interaction and an order of presentation vs. embedded-alone interaction."} {"id": "PMID:1255394", "title": "A statistical note on \"differential misdiagnosis of blacks and whites by the MMPI\".", "content": "This report presents a critique of the conclusion by Strauss et al, that MMPI diagnostic decision-making rules derived from whites are inapplicable to blacks. It is shown that for the data from two of their three MMPI indices, a multiple discriminant function and the Goldberg Index, there was no clear evidence for greater misdiagnosis among blacks than whites when the hit rates among psychotics, behavior disorders or both are examined. For the third measure, semiactuarial profile analysis, the results show less diagnostic accuracy for blacks psychotics, but this one result does not warrant a broad generalization. A preferable method of analysis and a source of potential bias in one of the measures are pointed out.", "contents": "A statistical note on \"differential misdiagnosis of blacks and whites by the MMPI\". This report presents a critique of the conclusion by Strauss et al, that MMPI diagnostic decision-making rules derived from whites are inapplicable to blacks. It is shown that for the data from two of their three MMPI indices, a multiple discriminant function and the Goldberg Index, there was no clear evidence for greater misdiagnosis among blacks than whites when the hit rates among psychotics, behavior disorders or both are examined. For the third measure, semiactuarial profile analysis, the results show less diagnostic accuracy for blacks psychotics, but this one result does not warrant a broad generalization. A preferable method of analysis and a source of potential bias in one of the measures are pointed out."} {"id": "PMID:1255395", "title": "Extraversion: sociability and impulsivity?", "content": "The sociability and impulsivity components of extraversion were studied. Thirty experimental items were written to assess different aspects of sociability and impuslivity. These items, along with the 24 extraversion items of the MPI, were administered to 146 college students. Factor analyses of experimental items indicated that neither sociability nor impulsivity is unitary. Correlations among these sociability and impulsivity factors and the MPI extraversion items indicated that MPI extraversion is essentially a measure of one aspect of sociability: the quantity of social relationships. Extraversion touches on but does not adequately sample either the intensity (quality) of social relationships or aspects of impulsivity.", "contents": "Extraversion: sociability and impulsivity? The sociability and impulsivity components of extraversion were studied. Thirty experimental items were written to assess different aspects of sociability and impuslivity. These items, along with the 24 extraversion items of the MPI, were administered to 146 college students. Factor analyses of experimental items indicated that neither sociability nor impulsivity is unitary. Correlations among these sociability and impulsivity factors and the MPI extraversion items indicated that MPI extraversion is essentially a measure of one aspect of sociability: the quantity of social relationships. Extraversion touches on but does not adequately sample either the intensity (quality) of social relationships or aspects of impulsivity."} {"id": "PMID:1255396", "title": "Primitive drive-dominated thinking: relationship to acute schizophrenia and sociopathy.", "content": "To investigate primitive drive-dominated thinking in schizophrenic disorders and sociopathic behavior, responses on the Rorschach and other personality tests of 171 acute psychiatric patients were assessed using Holt's system. Results suggested that: (a) Acute schizophrenics were high on primitive drive content, but this was also characteristic of some nonschizophrenics, and other types of disturbed thinking were even more prominent in schizophrenics. (b) There were no significant differences between process and reactive schizophrenics in expression of primitive drive content. (c) Males showed more drive-dominated thinking than females (p less than .10), although sex was not a powerful variable. (d) Depressives showed less drived-dominated thinking than nondepressive (p less than .05). (e) Patients high on sociopathic or rule-breaking behavior tended to show more primitive drive-dominated thinking (p less than .01).", "contents": "Primitive drive-dominated thinking: relationship to acute schizophrenia and sociopathy. To investigate primitive drive-dominated thinking in schizophrenic disorders and sociopathic behavior, responses on the Rorschach and other personality tests of 171 acute psychiatric patients were assessed using Holt's system. Results suggested that: (a) Acute schizophrenics were high on primitive drive content, but this was also characteristic of some nonschizophrenics, and other types of disturbed thinking were even more prominent in schizophrenics. (b) There were no significant differences between process and reactive schizophrenics in expression of primitive drive content. (c) Males showed more drive-dominated thinking than females (p less than .10), although sex was not a powerful variable. (d) Depressives showed less drived-dominated thinking than nondepressive (p less than .05). (e) Patients high on sociopathic or rule-breaking behavior tended to show more primitive drive-dominated thinking (p less than .01)."} {"id": "PMID:1255397", "title": "Factor specific differences in locus of control for emotionally disturbed and normal children.", "content": "The Nowicki-Strickland Locus of Control Scale for Children was given to 20 normal and 20 emotionally disturbed children to investigate the differences between the two groups on self-reported locus of control. The locus of control score and scores for each separate factor were calculated. Separate analyses of variance indicated that emotionally disturbed children did not differ from normals on overall locus of control nor on four of the five factors. However, one factor, Helplessness, differentiated the two groups with emotionally disturbed children endorsing more Helplessness items. The results are discussed in terms of factor specific methodology and in regards to the clinical relevance of Helplessness as a key factor.", "contents": "Factor specific differences in locus of control for emotionally disturbed and normal children. The Nowicki-Strickland Locus of Control Scale for Children was given to 20 normal and 20 emotionally disturbed children to investigate the differences between the two groups on self-reported locus of control. The locus of control score and scores for each separate factor were calculated. Separate analyses of variance indicated that emotionally disturbed children did not differ from normals on overall locus of control nor on four of the five factors. However, one factor, Helplessness, differentiated the two groups with emotionally disturbed children endorsing more Helplessness items. The results are discussed in terms of factor specific methodology and in regards to the clinical relevance of Helplessness as a key factor."} {"id": "PMID:1255398", "title": "Self-image disparity, repression-sensitization, and extraversion-introversion: a unitary dimension?", "content": "To determination (1) whether self-image disparity, repression-sensitization, and extraversion-introversion intercorrelated to a degree indicative of a unitary personality dimension and, (2) whether the interrelationships among these variables was accounted for by cognitive developmental variance, Byrne's Revised Repression-Sensitization Scale, Giedt and Downing's Extraversion-Introversion Scale, and two measures of self-image disparity were administered to 20 male college freshmen and 20 male seniors. All the correlations among the four measures were significant, but none correlated significantly with cognitive development, as measured by SATs. Factor analysis yielded a clearcut personality factor and a clearcut cognitive factor, indicating that the personality measures reflect a unitary dimension, even after cognitive developmental variance is extracted.", "contents": "Self-image disparity, repression-sensitization, and extraversion-introversion: a unitary dimension? To determination (1) whether self-image disparity, repression-sensitization, and extraversion-introversion intercorrelated to a degree indicative of a unitary personality dimension and, (2) whether the interrelationships among these variables was accounted for by cognitive developmental variance, Byrne's Revised Repression-Sensitization Scale, Giedt and Downing's Extraversion-Introversion Scale, and two measures of self-image disparity were administered to 20 male college freshmen and 20 male seniors. All the correlations among the four measures were significant, but none correlated significantly with cognitive development, as measured by SATs. Factor analysis yielded a clearcut personality factor and a clearcut cognitive factor, indicating that the personality measures reflect a unitary dimension, even after cognitive developmental variance is extracted."} {"id": "PMID:1255399", "title": "WAIS picture arrangement and premorbid social competence among process schizophrenics.", "content": "A study with male process schizophrenics suggested that the Picture Arrangement (PA) subtest of the WAIS was related to a measure of social competence. There was evidence that the PA subtest may measure an entity such as social intelligence which is different from overall intelligence.", "contents": "WAIS picture arrangement and premorbid social competence among process schizophrenics. A study with male process schizophrenics suggested that the Picture Arrangement (PA) subtest of the WAIS was related to a measure of social competence. There was evidence that the PA subtest may measure an entity such as social intelligence which is different from overall intelligence."} {"id": "PMID:1255400", "title": "On the assessment of sexual orientation: a reply to Anderson.", "content": "In response to Anderson's (1975) objections to Stone and Schneider's validation study of the Wheeler signs of homosexuality in the Rorschach, both the scientific and ethical-moral grounds for assessing sexual orientation were discussed. With respect to these two issues, it was argued that (a) an individual's sexual behaviors and attitudes, which includes sexual object preference, exert a significant influence on major portions of an individual's life and thus requires clinical assessment, and (b) only by gathering knowledge about human functioning in all domains can we effectively combat inappropriate stereotyping and prejudice, such as that which still exists towards homosexuals today.", "contents": "On the assessment of sexual orientation: a reply to Anderson. In response to Anderson's (1975) objections to Stone and Schneider's validation study of the Wheeler signs of homosexuality in the Rorschach, both the scientific and ethical-moral grounds for assessing sexual orientation were discussed. With respect to these two issues, it was argued that (a) an individual's sexual behaviors and attitudes, which includes sexual object preference, exert a significant influence on major portions of an individual's life and thus requires clinical assessment, and (b) only by gathering knowledge about human functioning in all domains can we effectively combat inappropriate stereotyping and prejudice, such as that which still exists towards homosexuals today."} {"id": "PMID:1255401", "title": "Evaluation of ego strength based on certain Rorschach variables.", "content": "Despite the importance of the assessment of ego strength for appropriate assignment of clients for psychotherapy and/or rehabilitation, existing techniques have not fulfilled expectations. A method for assessing ego strength through the Rorschach Test independent of clinical criterion is proposed. In addition to certain variables of Klopfer's RPRS (M+, FM+, FC+ plus CF+), sharply preceived space responses are included. They constitute a highly intercorrelated global measure of ego strength and are also highly correlated to a relatively independent Rorschach variable of global ego efficiency, i.e. integrated whole responses. In accordance with prediction, non-controlled color responses as well as accuracy of form perception did not correlate in a non-clinical sample with either measure of ego strength.", "contents": "Evaluation of ego strength based on certain Rorschach variables. Despite the importance of the assessment of ego strength for appropriate assignment of clients for psychotherapy and/or rehabilitation, existing techniques have not fulfilled expectations. A method for assessing ego strength through the Rorschach Test independent of clinical criterion is proposed. In addition to certain variables of Klopfer's RPRS (M+, FM+, FC+ plus CF+), sharply preceived space responses are included. They constitute a highly intercorrelated global measure of ego strength and are also highly correlated to a relatively independent Rorschach variable of global ego efficiency, i.e. integrated whole responses. In accordance with prediction, non-controlled color responses as well as accuracy of form perception did not correlate in a non-clinical sample with either measure of ego strength."} {"id": "PMID:1255408", "title": "Chemical constituents of fruit of Cocculus carolinus D.C. (Menispermaceae).", "content": "A phytochemical investigation of an ethanolic extract of the fruit of Cocculus carolinus resulted in the isolation and characterization of the alkaloids, cocculolidine and cocculine. The cyccculine, magnoflorine, and palmatine, previously reported in the stems and leaves of this species, were also isolated and identified.", "contents": "Chemical constituents of fruit of Cocculus carolinus D.C. (Menispermaceae). A phytochemical investigation of an ethanolic extract of the fruit of Cocculus carolinus resulted in the isolation and characterization of the alkaloids, cocculolidine and cocculine. The cyccculine, magnoflorine, and palmatine, previously reported in the stems and leaves of this species, were also isolated and identified."} {"id": "PMID:1255409", "title": "Synthesis of 5-hydroxy-1-((5-(p-nitrophenyl)furfurylidene)-amino) hydantoin, a metabolite of dantrolene.", "content": "The synthesis and structural elucidation of 5-hydroxyl-1-[[5-(p-nitrophenyl)furfurylidene]amino]hydantoin, a compound proposed as a metabolite of dantrolene sodium, are reported. In addition, a chromatographic comparison of the biological and synthesized materials is made.", "contents": "Synthesis of 5-hydroxy-1-((5-(p-nitrophenyl)furfurylidene)-amino) hydantoin, a metabolite of dantrolene. The synthesis and structural elucidation of 5-hydroxyl-1-[[5-(p-nitrophenyl)furfurylidene]amino]hydantoin, a compound proposed as a metabolite of dantrolene sodium, are reported. In addition, a chromatographic comparison of the biological and synthesized materials is made."} {"id": "PMID:1255411", "title": "Single-tablet enantiomeric purity assay of amphetamine by rotation enhancement.", "content": "Enhancement of the optical rotation of dextroamphetamine by production of an optically active chromophore through reaction with 1-fluoro-2,4-dinitrobenzene to give alpha-methPYL-N-(2,4-dinitrophenyl)-beta-phenylethylamine is reported. This reaction forms the basis of an assay for both the content and optical purity of dextroamphetamine sulfate at single-dose levels (5 mg). Results of assays of standard solutions and of commercial tablets demonstrate the suitability of the method for the determination of enantiomeric purity and amphetamine content.", "contents": "Single-tablet enantiomeric purity assay of amphetamine by rotation enhancement. Enhancement of the optical rotation of dextroamphetamine by production of an optically active chromophore through reaction with 1-fluoro-2,4-dinitrobenzene to give alpha-methPYL-N-(2,4-dinitrophenyl)-beta-phenylethylamine is reported. This reaction forms the basis of an assay for both the content and optical purity of dextroamphetamine sulfate at single-dose levels (5 mg). Results of assays of standard solutions and of commercial tablets demonstrate the suitability of the method for the determination of enantiomeric purity and amphetamine content."} {"id": "PMID:1255412", "title": "Pharmacological assessment of 3-tert-butylsydnone.", "content": "The pharmacological effects of the mesoionic derivative, 3-tert-butylsydnone, were investigated. Administration to rats caused clonic convulsions. The CD50 of 3-tert-butylsydnone was 0.471 +/- 0.033 mmole/kg. Trimethadione, but not phenytoin sodium or proadifen hydrochloride, protected the rat from the effects of 3-tert-butylsydnone. After administration of this compound, pentobarbital sodium sleeping time was reduced in the rat, but blood pressure and ECG were unchanged in the dog. Pretreatment of the mouse with 3-tert-butylsydnone did not influence the LD50 of epinephrine hydrochloride. The action of methacholine chloride in the rat was not blocked, and the pupil of the rabbit eye was unaffected. Tests for analgesic and oxytocic activity were negative. Chronic administration of a small dose to the rat for 70 days had no effect on blood glucose, blood urea nitrogen, hemoglobin, or microhematocrit values.", "contents": "Pharmacological assessment of 3-tert-butylsydnone. The pharmacological effects of the mesoionic derivative, 3-tert-butylsydnone, were investigated. Administration to rats caused clonic convulsions. The CD50 of 3-tert-butylsydnone was 0.471 +/- 0.033 mmole/kg. Trimethadione, but not phenytoin sodium or proadifen hydrochloride, protected the rat from the effects of 3-tert-butylsydnone. After administration of this compound, pentobarbital sodium sleeping time was reduced in the rat, but blood pressure and ECG were unchanged in the dog. Pretreatment of the mouse with 3-tert-butylsydnone did not influence the LD50 of epinephrine hydrochloride. The action of methacholine chloride in the rat was not blocked, and the pupil of the rabbit eye was unaffected. Tests for analgesic and oxytocic activity were negative. Chronic administration of a small dose to the rat for 70 days had no effect on blood glucose, blood urea nitrogen, hemoglobin, or microhematocrit values."} {"id": "PMID:1255413", "title": "Determination of nitroimidazoles in biological fluids by differential pulse polarography.", "content": "A sensitive differential pulse polarographic assay was developed for the determination of metronidazole, ornidazole, and 2-nitro-1H-imidazole-1-(3-methoxy-2-propanol) in plasma. The compounds are selectively extracted into ethyl acetate from a protein-free filtrate of plasma, buffered to pH 7.0 +/- 0.2. The residue of the ethyl acetate extract is dissolved in 0.1 N NaOH and analyzed by differential pulse polarography for the reduction of the nitro group at approximately -0.600 v versus the saturated calomel electrode. The overall recovery from plasma was about 55 +/- 3.0% (SD) for the three compounds investigated. A TLC step after the ethyl acetate extraction may also be included to ensure specificity. This step reduced the overall recovery to approximately 45%. The sensitivity limit of detection from plasma using a 2-ml sample is 0.1 mug/ml. The assay may also be employed for the analysis of urine. The urine is adjusted to pH 7.0 +/- 0.2 and extracted with ethyl acetate, and the residue is analyzed as described for plasma. The assay was applied to the determination of ornidazole in blood and urine in the dog following 10 mg/kg po.", "contents": "Determination of nitroimidazoles in biological fluids by differential pulse polarography. A sensitive differential pulse polarographic assay was developed for the determination of metronidazole, ornidazole, and 2-nitro-1H-imidazole-1-(3-methoxy-2-propanol) in plasma. The compounds are selectively extracted into ethyl acetate from a protein-free filtrate of plasma, buffered to pH 7.0 +/- 0.2. The residue of the ethyl acetate extract is dissolved in 0.1 N NaOH and analyzed by differential pulse polarography for the reduction of the nitro group at approximately -0.600 v versus the saturated calomel electrode. The overall recovery from plasma was about 55 +/- 3.0% (SD) for the three compounds investigated. A TLC step after the ethyl acetate extraction may also be included to ensure specificity. This step reduced the overall recovery to approximately 45%. The sensitivity limit of detection from plasma using a 2-ml sample is 0.1 mug/ml. The assay may also be employed for the analysis of urine. The urine is adjusted to pH 7.0 +/- 0.2 and extracted with ethyl acetate, and the residue is analyzed as described for plasma. The assay was applied to the determination of ornidazole in blood and urine in the dog following 10 mg/kg po."} {"id": "PMID:1255414", "title": "Effect of dioctyl sodium sulfosuccinate and poloxamer 188 on dissolution and intestinal absorption of sulfadiazine and sulfisoxazole in rats.", "content": "The influence of two medicinal surfactants, poloxamer 188 and dioctyl sodium sulfosuccinate, on the dissolution of sulfisoxazole and sulfadiazine was investigated. A dramatic increase in the dissolution rate was observed at all surfactant concentrations. Drug absorption from the rat small intestine was also studied, and a significant but less dramatic increase was noted. Dissolution rate and absorption could be correlated only qualitatively. The two surfactants had no effect on the amount of sulfisoxazole excreted by the rat in 24 hr.", "contents": "Effect of dioctyl sodium sulfosuccinate and poloxamer 188 on dissolution and intestinal absorption of sulfadiazine and sulfisoxazole in rats. The influence of two medicinal surfactants, poloxamer 188 and dioctyl sodium sulfosuccinate, on the dissolution of sulfisoxazole and sulfadiazine was investigated. A dramatic increase in the dissolution rate was observed at all surfactant concentrations. Drug absorption from the rat small intestine was also studied, and a significant but less dramatic increase was noted. Dissolution rate and absorption could be correlated only qualitatively. The two surfactants had no effect on the amount of sulfisoxazole excreted by the rat in 24 hr."} {"id": "PMID:1255415", "title": "Polarographic determination of isosorbide dinitrate.", "content": "Isosorbide dinitrate and two isomeric isosorbide mononitrates are shown to be polarographically reducible in aqueous sodium perchlorate or potassium chloride solution. The current, measured at -1.6 v, versus the saturated calomel electrode is proportional to the concentration of organic nitrate in the 10-100-mug/ml range. Inorganic nitrate produces no interference. However, the mononitrate isomers produce an additive response to isosorbide dinitrate and cannot be determined individually. The polarographic method is applicable to single-tablet assay for content uniformity determination, with precision and accuracy comparable to automated colorimetric analysis. Comparison is made between replicate analyses obtained polarographically and by IR and automated colorimetric analysis for six different commercially available formulations. The polarographic determination is sensitive, specific for nitrate esters, precise, requires little sample preparation, and utilizes relatively inexpensive apparatus.", "contents": "Polarographic determination of isosorbide dinitrate. Isosorbide dinitrate and two isomeric isosorbide mononitrates are shown to be polarographically reducible in aqueous sodium perchlorate or potassium chloride solution. The current, measured at -1.6 v, versus the saturated calomel electrode is proportional to the concentration of organic nitrate in the 10-100-mug/ml range. Inorganic nitrate produces no interference. However, the mononitrate isomers produce an additive response to isosorbide dinitrate and cannot be determined individually. The polarographic method is applicable to single-tablet assay for content uniformity determination, with precision and accuracy comparable to automated colorimetric analysis. Comparison is made between replicate analyses obtained polarographically and by IR and automated colorimetric analysis for six different commercially available formulations. The polarographic determination is sensitive, specific for nitrate esters, precise, requires little sample preparation, and utilizes relatively inexpensive apparatus."} {"id": "PMID:1255416", "title": "Inhibition of synaptosomal accumulation of l-norepinephrine II: N-aryloxyalkylphentermines, quaternary d-amphetamines, and 3-aryloxypropylamines.", "content": "The inhibitory potencies of a series of N-substituted phentermines on the synaptosomal uptake of l-norepinephrine were found to be similar to those of the corresponding amphetamines. Quaternization of N, N-dimenthyl-d-amphetamine diminished, but did not abolish, its inhibitory potency, indicating that a permanently charged cation is also effective. Since the addition of an aromatic moiety at the end of a four-atom chain originating at the nitrogen of amphetamine or phentermine significantly increased inhibitor strength, several 3-aryloxypropylamines and 4-phenylbutylamine were tested, but they were much weaker inhibitors than dl-amphetamine. Thus, the observed increase in inhibitor potency apparently was not simply the result of a specific interaction of the \"nonmimic\" portion of the N-substituted amphetamines or phentermines.", "contents": "Inhibition of synaptosomal accumulation of l-norepinephrine II: N-aryloxyalkylphentermines, quaternary d-amphetamines, and 3-aryloxypropylamines. The inhibitory potencies of a series of N-substituted phentermines on the synaptosomal uptake of l-norepinephrine were found to be similar to those of the corresponding amphetamines. Quaternization of N, N-dimenthyl-d-amphetamine diminished, but did not abolish, its inhibitory potency, indicating that a permanently charged cation is also effective. Since the addition of an aromatic moiety at the end of a four-atom chain originating at the nitrogen of amphetamine or phentermine significantly increased inhibitor strength, several 3-aryloxypropylamines and 4-phenylbutylamine were tested, but they were much weaker inhibitors than dl-amphetamine. Thus, the observed increase in inhibitor potency apparently was not simply the result of a specific interaction of the \"nonmimic\" portion of the N-substituted amphetamines or phentermines."} {"id": "PMID:1255417", "title": "Synthesis and biological evaluation of tetrakis(acetylsalicylato)-mu-dicopper(II).", "content": "The synthesis of a copper-aspirin chelate, previously reported to be a more active anti-inflammatory agent than aspirin itself, is given. Reaction of potassium acetylsalicylate with cupric sulfate gave a stable copper complex, which analysis and molecular weight determination showed to be a 4:2 chelate structure. Oil-water partition measurements showed the complex to be 10-fold more oil soluble than aspirin. Biological evaluation in rats showed the copper complex of aspirin to be approximately equal to aspirin in reducing carrageenan-induced inflammation, but it was 1.7 times more active than aspirin in reducing the primary lesion of adjuvant arthritis. Whereas aspirin produced a 50% or greater incidence of GI erosions at doses of 100-300 mg/kg in rats, the copper complex caused no erosions in doses up to 1200 mg/kg.", "contents": "Synthesis and biological evaluation of tetrakis(acetylsalicylato)-mu-dicopper(II). The synthesis of a copper-aspirin chelate, previously reported to be a more active anti-inflammatory agent than aspirin itself, is given. Reaction of potassium acetylsalicylate with cupric sulfate gave a stable copper complex, which analysis and molecular weight determination showed to be a 4:2 chelate structure. Oil-water partition measurements showed the complex to be 10-fold more oil soluble than aspirin. Biological evaluation in rats showed the copper complex of aspirin to be approximately equal to aspirin in reducing carrageenan-induced inflammation, but it was 1.7 times more active than aspirin in reducing the primary lesion of adjuvant arthritis. Whereas aspirin produced a 50% or greater incidence of GI erosions at doses of 100-300 mg/kg in rats, the copper complex caused no erosions in doses up to 1200 mg/kg."} {"id": "PMID:1255418", "title": "Transfer of alcohols and ureas across the oral mucosa measured using streaming potentials and radioisotopes.", "content": "The permeability of the oral mucosa to an alcohol and a urea series was studied using radioisotope transfer and the measurement of streaming potentials. Both methods yielded similar quantitative estimates of permeability. The rate of transfer of the smallest member of both series (methanol and urea) was greater than the second member (ethanol and methylurea). In the alcohol series, permeability increased as the chain length increased from ethanol to butanol. In contrast, the permeability of the oral mucosa to ethylurea and propylurea was less than to methylurea. However, butylurea had a greater rate of transfer than either propylurea or ethylurea.", "contents": "Transfer of alcohols and ureas across the oral mucosa measured using streaming potentials and radioisotopes. The permeability of the oral mucosa to an alcohol and a urea series was studied using radioisotope transfer and the measurement of streaming potentials. Both methods yielded similar quantitative estimates of permeability. The rate of transfer of the smallest member of both series (methanol and urea) was greater than the second member (ethanol and methylurea). In the alcohol series, permeability increased as the chain length increased from ethanol to butanol. In contrast, the permeability of the oral mucosa to ethylurea and propylurea was less than to methylurea. However, butylurea had a greater rate of transfer than either propylurea or ethylurea."} {"id": "PMID:1255419", "title": "Mild and safe procedure for hydrolyzing oximes: improved synthesis of 1,2-indandione.", "content": "Four ketoximes were hydrolyzed to the corresponding ketones in 66-91% yields using 75% sulfuric acid and 37% formaldehyde at room temperature. An earlier procedure involving hydrochloric acid and 37% formaldehyde is extremely hazardous because it leads to the formation of bis(chloromethyl) ether, a potent carcinogen.", "contents": "Mild and safe procedure for hydrolyzing oximes: improved synthesis of 1,2-indandione. Four ketoximes were hydrolyzed to the corresponding ketones in 66-91% yields using 75% sulfuric acid and 37% formaldehyde at room temperature. An earlier procedure involving hydrochloric acid and 37% formaldehyde is extremely hazardous because it leads to the formation of bis(chloromethyl) ether, a potent carcinogen."} {"id": "PMID:1255420", "title": "Rapid TLC determination of methadyl acetate and some in vitro metabolites.", "content": "Methadyl acetate was metabolized by microsomal preparations of rat liver to yield nor-methadyl acetate and 6-(dimethylamino)-4,4-diphenyl-3-heptanol. The identification and separation of these three compounds was established by TLC, using iodoplatinate spray as a visualizing agent.", "contents": "Rapid TLC determination of methadyl acetate and some in vitro metabolites. Methadyl acetate was metabolized by microsomal preparations of rat liver to yield nor-methadyl acetate and 6-(dimethylamino)-4,4-diphenyl-3-heptanol. The identification and separation of these three compounds was established by TLC, using iodoplatinate spray as a visualizing agent."} {"id": "PMID:1255421", "title": "Time-dependent change in renal clearance of bethanidine in humans.", "content": "Blood levels and urinary excretion rates of bethanidine were determined in three normal human subjects following oral administration of a single dose of the drug. The postabsorptive decline of blood concentration with time was noticeably slower than the corresponding decline in the urinary excretion rate. The discrepancy can be attributed to a continual decrease in the renal clearance of bethanidine throughout the study. Therefore, pharmacokinetic modeling of urinary excretion data alone would lead to erroneous conclusions concerning the persistence of drug in the blood.", "contents": "Time-dependent change in renal clearance of bethanidine in humans. Blood levels and urinary excretion rates of bethanidine were determined in three normal human subjects following oral administration of a single dose of the drug. The postabsorptive decline of blood concentration with time was noticeably slower than the corresponding decline in the urinary excretion rate. The discrepancy can be attributed to a continual decrease in the renal clearance of bethanidine throughout the study. Therefore, pharmacokinetic modeling of urinary excretion data alone would lead to erroneous conclusions concerning the persistence of drug in the blood."} {"id": "PMID:1255422", "title": "New compounds: synthesis of carboxymethyl carbodithioates.", "content": "The synthesis and characterization of some new carboxymethyl carbodithioates are reported.", "contents": "New compounds: synthesis of carboxymethyl carbodithioates. The synthesis and characterization of some new carboxymethyl carbodithioates are reported."} {"id": "PMID:1255429", "title": "Glass for parenteral products: a surface view using the scanning electron microscope.", "content": "The scanning electron microscope was utilized to explore the internal surface of glass ampuls and vials used in parenteral products. The surface topography of USP Type I borosilicate glass containers was viewed after exposure to \"sulfur,\" ammonium bifluoride, and sulfuric acid treatments. The scanning electron micrographs showed startling differences in the appearance of the surface regions. \"Sulfur treatment\" of ampuls was associated with a pitting of the surface and the presence of sodium sulfate crystals. The sulfur treatment of vials altered the glass surface in a characteristically different manner. The dissimilarity between the surface appearances was attributed to the method of sulfur treatment. Ampuls exposed to sulfuric acid solutions at room temperature did not show the pitting associated with the sulfur treatment. Scanning electron micrographs of ammonium bifluoride-treated ampuls showed a relief effect, suggesting that the glass was affected by the bifluoride solution but that sufficient stripping of the surface layer did not occur to remove the pits associated with the sulfur treatment. Flakes emanating from the glass were identified with the aid of the electron microprobe. Scanning electron micrographs showed that these vitreous flakes resulted from a delamination of a thin layer of the glass surface. It is concluded that the scanning electron microscope, in conjunction with other analytical techniques, is a valuable tool in assessing the quality of glass used for parenteral products. The techniques studied should be of particular importance to the pharmaceutical industry where efforts are being made to reduce the levels of particulate matter in parenteral dosage forms.", "contents": "Glass for parenteral products: a surface view using the scanning electron microscope. The scanning electron microscope was utilized to explore the internal surface of glass ampuls and vials used in parenteral products. The surface topography of USP Type I borosilicate glass containers was viewed after exposure to \"sulfur,\" ammonium bifluoride, and sulfuric acid treatments. The scanning electron micrographs showed startling differences in the appearance of the surface regions. \"Sulfur treatment\" of ampuls was associated with a pitting of the surface and the presence of sodium sulfate crystals. The sulfur treatment of vials altered the glass surface in a characteristically different manner. The dissimilarity between the surface appearances was attributed to the method of sulfur treatment. Ampuls exposed to sulfuric acid solutions at room temperature did not show the pitting associated with the sulfur treatment. Scanning electron micrographs of ammonium bifluoride-treated ampuls showed a relief effect, suggesting that the glass was affected by the bifluoride solution but that sufficient stripping of the surface layer did not occur to remove the pits associated with the sulfur treatment. Flakes emanating from the glass were identified with the aid of the electron microprobe. Scanning electron micrographs showed that these vitreous flakes resulted from a delamination of a thin layer of the glass surface. It is concluded that the scanning electron microscope, in conjunction with other analytical techniques, is a valuable tool in assessing the quality of glass used for parenteral products. The techniques studied should be of particular importance to the pharmaceutical industry where efforts are being made to reduce the levels of particulate matter in parenteral dosage forms."} {"id": "PMID:1255430", "title": "Determination of coumarin and umbelliferone mixtures in whole blood by spectrophotofluorometry.", "content": "A spectrophotofluorometric method is described for the quantitative analysis of coumarin, umbelliferone, and mixtures thereof in whole blood. The two drugs were selectively isolated from blood by solvent extraction. Analysis of the isolated coumarin was based on the measurement of the fluorophore at activation and emission wavelengths of 361 and 491 nm, respectively. The fluorophore was obtained by irradiating an alkaline methanolic solution of the drug with UV light. A linear relationship between fluorescence and concentration existed over the concentration range of 0.02-0.2 mug of coumarin/ml. A mean recovery value of 94.8% was obtained from whole blood. The isolated umbelliferone was determined according to established methods at activation and emission wavelengths of 370 and 450 nm, respectively, and the limit of detection was 10 times more sensitive than previously reported. A linearity response was obtained between 1 and 10 ng of umbelliferone/ml. Good recovery data for mixtures of coumarin and umbelliferone in whole blood were obtained.", "contents": "Determination of coumarin and umbelliferone mixtures in whole blood by spectrophotofluorometry. A spectrophotofluorometric method is described for the quantitative analysis of coumarin, umbelliferone, and mixtures thereof in whole blood. The two drugs were selectively isolated from blood by solvent extraction. Analysis of the isolated coumarin was based on the measurement of the fluorophore at activation and emission wavelengths of 361 and 491 nm, respectively. The fluorophore was obtained by irradiating an alkaline methanolic solution of the drug with UV light. A linear relationship between fluorescence and concentration existed over the concentration range of 0.02-0.2 mug of coumarin/ml. A mean recovery value of 94.8% was obtained from whole blood. The isolated umbelliferone was determined according to established methods at activation and emission wavelengths of 370 and 450 nm, respectively, and the limit of detection was 10 times more sensitive than previously reported. A linearity response was obtained between 1 and 10 ng of umbelliferone/ml. Good recovery data for mixtures of coumarin and umbelliferone in whole blood were obtained."} {"id": "PMID:1255431", "title": "Binding of salicylate and sulfathiazole by whole blood constituents.", "content": "The binding of salicylic acid and sulfathiazole to bovine whole blood, plasma proteins, and purified albumin fraction was investigated using a dynamic dialysis system. The binding profiles for salicylic acid were quite similar in bovine plasma and 4% bovine serum albumin. In contrast, the binding of sulfathiazole was significantly greater in the plasma than in solutions of fraction V bovine serum albumin. Data from dynamic dialysis binding studies of the compounds, conducted in whole blood and suspended erythrocyte systems, did not lend themselves to analysis by classical methods. Hemolysis and alteration in the nature of the protein binding sites during the binding studies were shown to be factors that could explain the unusual binding observed in the whole blood system.", "contents": "Binding of salicylate and sulfathiazole by whole blood constituents. The binding of salicylic acid and sulfathiazole to bovine whole blood, plasma proteins, and purified albumin fraction was investigated using a dynamic dialysis system. The binding profiles for salicylic acid were quite similar in bovine plasma and 4% bovine serum albumin. In contrast, the binding of sulfathiazole was significantly greater in the plasma than in solutions of fraction V bovine serum albumin. Data from dynamic dialysis binding studies of the compounds, conducted in whole blood and suspended erythrocyte systems, did not lend themselves to analysis by classical methods. Hemolysis and alteration in the nature of the protein binding sites during the binding studies were shown to be factors that could explain the unusual binding observed in the whole blood system."} {"id": "PMID:1255432", "title": "Comparison of antimicrobial activity of nuclear-substituted aromatic esters of 5-dimethylamino-1-phenyl-3-pentanol and 3-dimethylamino-1-phenyl-1-propanol with related cyclic analogs.", "content": "A series of six aromatic esters of both 5-dimethyl-amino-1-phenyl-3-pentanol and 3-dimethylamino-1-(2-phenylcyclohexyl)-1-propanol was prepared. Antimicrobial evaluation showed that the cyclic analogs had approximately twice the activity of the open chain series; in particular, the o-chlorophenyl ester showed pronounced activity against three pathogenic fungi at approximately 10 ppm. Aromatic esters of 3-dimethylamino-1-phenyl-1-propanol were prepared and demonstrated lower activity than two esters of 2-dimethylamino-1-phenylcyclohexanol. The screening results showed that the best activity was found when a dimethylene chain was present between the phenyl ring and the carbon atom bearing the acyloxy function and that the cyclic derivatives were more active than their more flexible counterparts.", "contents": "Comparison of antimicrobial activity of nuclear-substituted aromatic esters of 5-dimethylamino-1-phenyl-3-pentanol and 3-dimethylamino-1-phenyl-1-propanol with related cyclic analogs. A series of six aromatic esters of both 5-dimethyl-amino-1-phenyl-3-pentanol and 3-dimethylamino-1-(2-phenylcyclohexyl)-1-propanol was prepared. Antimicrobial evaluation showed that the cyclic analogs had approximately twice the activity of the open chain series; in particular, the o-chlorophenyl ester showed pronounced activity against three pathogenic fungi at approximately 10 ppm. Aromatic esters of 3-dimethylamino-1-phenyl-1-propanol were prepared and demonstrated lower activity than two esters of 2-dimethylamino-1-phenylcyclohexanol. The screening results showed that the best activity was found when a dimethylene chain was present between the phenyl ring and the carbon atom bearing the acyloxy function and that the cyclic derivatives were more active than their more flexible counterparts."} {"id": "PMID:1255433", "title": "Spectrophotometric determination of sodium nitroprusside and its photodegradation products.", "content": "A specific spectrophotometric method of analysis for sodium nitroprusside was developed utilizing the molar absorptivity values at the maxima appearing in the electronic spectrum at 394 and 498 nm that may be attributed to metal d leading to pi* NO transitions. These measurements appear to be indicative of the unaltered nitroferricyanide complex. A reaction sequence is postulated for aqueous solutions of nitroprusside exposed to normal artificial light. Evidence suggests that one species in the sequence is nitroferricyanide in a higher energy state but with the nitrosyl moiety still present in the coordination sphere, which exhibits an increased molar absorptivity at 394 nm. The molar absorptivity at the 498-nm maximum remains unchanged. Corroborating polarographic data are presented.", "contents": "Spectrophotometric determination of sodium nitroprusside and its photodegradation products. A specific spectrophotometric method of analysis for sodium nitroprusside was developed utilizing the molar absorptivity values at the maxima appearing in the electronic spectrum at 394 and 498 nm that may be attributed to metal d leading to pi* NO transitions. These measurements appear to be indicative of the unaltered nitroferricyanide complex. A reaction sequence is postulated for aqueous solutions of nitroprusside exposed to normal artificial light. Evidence suggests that one species in the sequence is nitroferricyanide in a higher energy state but with the nitrosyl moiety still present in the coordination sphere, which exhibits an increased molar absorptivity at 394 nm. The molar absorptivity at the 498-nm maximum remains unchanged. Corroborating polarographic data are presented."} {"id": "PMID:1255434", "title": "Effect of solvent flow Reynolds number on dissolution rate of a nondisintegrating solid (potassium chloride).", "content": "An apparatus for measuring dissolution rates of solids in the form of disks was designed to possess the following features. The solvent flowed continuously and reproducibly past the disk at various rates associated with calculable Reynolds numbers, Re. The effluent solution was adequately mixed before analysis. The concentration of dissolved solute was much less than the solubility. The surface area of the disk in contact with the solvent was constant during measurements. The dissolution rate of the disk was reproducible, and the disk and its surface could be readily characterized. The apparatus was tested at 37 degrees with compressed potassium chloride and water. The intrinsic dissolution rate, G, was a linear function of Re from Re=360 to greater than 6000. This relationship enabled one unknown constant in each dissolution theory to be expressed in terms of Re. For the diffusion layer model, the thickness of this layer, calculated from the experimental value of G, agreed well with that calculated from the various physical properties, provided that natural convection did not predominate. The dissolution of potassium chloride in this system was, therefore, controlled by diffusion.", "contents": "Effect of solvent flow Reynolds number on dissolution rate of a nondisintegrating solid (potassium chloride). An apparatus for measuring dissolution rates of solids in the form of disks was designed to possess the following features. The solvent flowed continuously and reproducibly past the disk at various rates associated with calculable Reynolds numbers, Re. The effluent solution was adequately mixed before analysis. The concentration of dissolved solute was much less than the solubility. The surface area of the disk in contact with the solvent was constant during measurements. The dissolution rate of the disk was reproducible, and the disk and its surface could be readily characterized. The apparatus was tested at 37 degrees with compressed potassium chloride and water. The intrinsic dissolution rate, G, was a linear function of Re from Re=360 to greater than 6000. This relationship enabled one unknown constant in each dissolution theory to be expressed in terms of Re. For the diffusion layer model, the thickness of this layer, calculated from the experimental value of G, agreed well with that calculated from the various physical properties, provided that natural convection did not predominate. The dissolution of potassium chloride in this system was, therefore, controlled by diffusion."} {"id": "PMID:1255435", "title": "Fluorocarbon aerosol propellants VIII: solubility of trichloromonofluoromethane in dog blood and tissue homogenates.", "content": "The solubility of trichloromonofluoromethane in dog blood and tissue homogenates was measured indirectly using the head-space method at 37 degrees. These values, except that in dog blood, were used to estimate the solubility in the whole tissues or organs. In most cases, the solubility so obtained was independent of equilibrium concentration. However, a considerable concentration dependence for the solubility was observed in dog heart and kidney. The highest solubility found was in dog fat versus air, i.e., 45.6, which is almost 220 times higher than the solubility in water or normal saline. Fat solubilization and specific binding interactions appeared to be the two major factors in determining the solubility. The pharmacokinetic implications of such findings are discussed.", "contents": "Fluorocarbon aerosol propellants VIII: solubility of trichloromonofluoromethane in dog blood and tissue homogenates. The solubility of trichloromonofluoromethane in dog blood and tissue homogenates was measured indirectly using the head-space method at 37 degrees. These values, except that in dog blood, were used to estimate the solubility in the whole tissues or organs. In most cases, the solubility so obtained was independent of equilibrium concentration. However, a considerable concentration dependence for the solubility was observed in dog heart and kidney. The highest solubility found was in dog fat versus air, i.e., 45.6, which is almost 220 times higher than the solubility in water or normal saline. Fat solubilization and specific binding interactions appeared to be the two major factors in determining the solubility. The pharmacokinetic implications of such findings are discussed."} {"id": "PMID:1255436", "title": "Fluorocarbon aerosol propellants IX: adsorption on activated charcoal.", "content": "The adsorption of three commonly used fluorocarbons, trichloromonofluoromethane, dichlorodifluoromethane, and dichlorotetrafluoroethane, on activated charcoal was studied at 25 degrees. The adsorption versus pressure plots are consistent with the Brunauer, Emmett, and Teller (BET) type II and type IV isotherms, which can be explained as the condensation of the gaseous molecules in a wide range of pores in the activated charcoal. The monolayer capacity derived from the BET equation is discussed and used to estimate the volume of micropores present in the activated charcoal. Below the relative pressure of 0.01, the adsorption deviated from the BET plot. The deviation revealed that the adsorption capacity and adsorption potential at these lower pressures are greater than the extrapolated values. It is concluded that activated charcoal can be used effectively to remove propellants from the air in pollution control.", "contents": "Fluorocarbon aerosol propellants IX: adsorption on activated charcoal. The adsorption of three commonly used fluorocarbons, trichloromonofluoromethane, dichlorodifluoromethane, and dichlorotetrafluoroethane, on activated charcoal was studied at 25 degrees. The adsorption versus pressure plots are consistent with the Brunauer, Emmett, and Teller (BET) type II and type IV isotherms, which can be explained as the condensation of the gaseous molecules in a wide range of pores in the activated charcoal. The monolayer capacity derived from the BET equation is discussed and used to estimate the volume of micropores present in the activated charcoal. Below the relative pressure of 0.01, the adsorption deviated from the BET plot. The deviation revealed that the adsorption capacity and adsorption potential at these lower pressures are greater than the extrapolated values. It is concluded that activated charcoal can be used effectively to remove propellants from the air in pollution control."} {"id": "PMID:1255437", "title": "Fluorocarbon aerosol propellants X: pharmacokinetics of dichlorotetrafluoroethane in dogs.", "content": "An intravenous dosage form of dichlorotetrafluoroethane, a common fluorocarbon aerosol propellant, was formulated in polyethylene glycol 400 for single dosing to unanesthetized dogs. A three-compartment open model was proposed for the disposition of this compound in dogs, with average half-lives of 1.3, 9.6, and 50.8 min for the three disposition phases. An analysis of tissue compartment distribution following a single dose showed that it took about 2 hr to achieve pseudo-distribution equilibration, following which more than 90% of the propellant remaining in the body was retained in the tissue compartments. Pulmonary clearance and volumes of distribution were calculated considering the first-pass effect through the lungs. The volume of distribution was approximately 10 times the body weight in terms of blood concentration, and about 84% of the propellant was cleared from the blood passing through the lungs in each cycle.", "contents": "Fluorocarbon aerosol propellants X: pharmacokinetics of dichlorotetrafluoroethane in dogs. An intravenous dosage form of dichlorotetrafluoroethane, a common fluorocarbon aerosol propellant, was formulated in polyethylene glycol 400 for single dosing to unanesthetized dogs. A three-compartment open model was proposed for the disposition of this compound in dogs, with average half-lives of 1.3, 9.6, and 50.8 min for the three disposition phases. An analysis of tissue compartment distribution following a single dose showed that it took about 2 hr to achieve pseudo-distribution equilibration, following which more than 90% of the propellant remaining in the body was retained in the tissue compartments. Pulmonary clearance and volumes of distribution were calculated considering the first-pass effect through the lungs. The volume of distribution was approximately 10 times the body weight in terms of blood concentration, and about 84% of the propellant was cleared from the blood passing through the lungs in each cycle."} {"id": "PMID:1255438", "title": "Mass spectral and pyrolytic behavior of the two main products of phenylbutazone degradation: simulation of unusual mass spectral fragmentation.", "content": "The two major routes of degradation of phenylbutazone (I) are oxidation and hydrolysis. Hydrolysis gives rise to n-butylmalonic acid mono(N,N'-diphenyl)hydrazide (II). Oxidation at the C-4 position yields 1,2-diphenyl-4-n-butyl-4-hydroxpyrazolidine-3,5-dione (III), which is readily hydrolyzed to n-butyltartronic acid mono-(N,N'-diphenyl)hydrazide (IV). Whereas the mass spectra of I, III, and the methyl esters of carboxylic acids II and IV all demonstrate major peaks corresponding to their respective molecular ions, the mass spectrum of II is essentially identical with that of I, suggesting facile dehydration. In the mass spectrum of IV, the peak of highest mass is found at m/e 205; no peak could be perceived corresponding to the molecular ion or to loss of water, carbon dioxide, or both of these elements from the molecular ion. Under normal pyrolytic conditions, II is decarboxylated to N-caproylhydrazobenzene (V) and IV is readily dehydrated to yield III. The mass spectral fragmentation of IV was successfully simulated in the laboratory to give an excellent yield of aniline and alpha-keto-N-caproylaniline (VI) (mol. wt. 205). The probable course of this unusual transformation was elucidated from studies of the accelerated decomposition of IV and derivatives considered as possible intermediates in the degradation process.", "contents": "Mass spectral and pyrolytic behavior of the two main products of phenylbutazone degradation: simulation of unusual mass spectral fragmentation. The two major routes of degradation of phenylbutazone (I) are oxidation and hydrolysis. Hydrolysis gives rise to n-butylmalonic acid mono(N,N'-diphenyl)hydrazide (II). Oxidation at the C-4 position yields 1,2-diphenyl-4-n-butyl-4-hydroxpyrazolidine-3,5-dione (III), which is readily hydrolyzed to n-butyltartronic acid mono-(N,N'-diphenyl)hydrazide (IV). Whereas the mass spectra of I, III, and the methyl esters of carboxylic acids II and IV all demonstrate major peaks corresponding to their respective molecular ions, the mass spectrum of II is essentially identical with that of I, suggesting facile dehydration. In the mass spectrum of IV, the peak of highest mass is found at m/e 205; no peak could be perceived corresponding to the molecular ion or to loss of water, carbon dioxide, or both of these elements from the molecular ion. Under normal pyrolytic conditions, II is decarboxylated to N-caproylhydrazobenzene (V) and IV is readily dehydrated to yield III. The mass spectral fragmentation of IV was successfully simulated in the laboratory to give an excellent yield of aniline and alpha-keto-N-caproylaniline (VI) (mol. wt. 205). The probable course of this unusual transformation was elucidated from studies of the accelerated decomposition of IV and derivatives considered as possible intermediates in the degradation process."} {"id": "PMID:1255439", "title": "Spectrophotometric determination of p-aminophenol alone or in the presence of acetaminophen.", "content": "Small amounts of p-aminophenol were analyzed quantitatively by mixing with 4-nitro- or 2,4-dinitrobenzaldehyde in neutral alcoholic solution and then quantitatively forming the respective Schiff bases, 4'-nitro- and 2',4'-dinitrobenzylidene-4-hydroxyaniline, by evaporating the alcoholic solutions to dryness. The Schiff bases thus formed were examined spectrophotometrically. This procedure was also used for the determination of p-aminophenol in the presence of its degradation products. It was necessary, however, to separate the respective Schiff bases by TLC from the degradation products and the reaction mixture prior to spectrophotometric examination. Small amounts of p-aminophenol present in acetaminophen were quantitatively determined by applying the procedure to a water-ethanol (95:5 v/v) extract of the samples of acetaminophen. TLC was used to separate the respective Schiff bases from the reaction mixture and acetaminophen prior to spectrophotometric examination.", "contents": "Spectrophotometric determination of p-aminophenol alone or in the presence of acetaminophen. Small amounts of p-aminophenol were analyzed quantitatively by mixing with 4-nitro- or 2,4-dinitrobenzaldehyde in neutral alcoholic solution and then quantitatively forming the respective Schiff bases, 4'-nitro- and 2',4'-dinitrobenzylidene-4-hydroxyaniline, by evaporating the alcoholic solutions to dryness. The Schiff bases thus formed were examined spectrophotometrically. This procedure was also used for the determination of p-aminophenol in the presence of its degradation products. It was necessary, however, to separate the respective Schiff bases by TLC from the degradation products and the reaction mixture prior to spectrophotometric examination. Small amounts of p-aminophenol present in acetaminophen were quantitatively determined by applying the procedure to a water-ethanol (95:5 v/v) extract of the samples of acetaminophen. TLC was used to separate the respective Schiff bases from the reaction mixture and acetaminophen prior to spectrophotometric examination."} {"id": "PMID:1255440", "title": "Fully automated analysis of phenylbutazone in plasma and urine.", "content": "A rapid, automated method for the determination of phenylbutazone in plasma and urine was developed. The method offers distinct advantages over earlier procedures and is particularly suitable for large-scale bioavailability studies.", "contents": "Fully automated analysis of phenylbutazone in plasma and urine. A rapid, automated method for the determination of phenylbutazone in plasma and urine was developed. The method offers distinct advantages over earlier procedures and is particularly suitable for large-scale bioavailability studies."} {"id": "PMID:1255441", "title": "GLC determination of quinidines in human plasma.", "content": "Human plasma was made alkaline and extracted with methylene chloride. To the extract was added the internal standard, cinchonine, followed by evaporation to dryness. The resultant residue was dissolved in a methanolic solution containing trimethylanilinium hydroxide. This solution was assayed by GLC for quinidines (quinidine and hydroquinidine). Evaluation of the method over a 0.5-10-mug/ml range in human plasma gave an overall precision and accuracy of +/- 4.5% (RSD and RE). Plasma of several patients was analyzed by the present method as well as by a fluorometric method for the level of quinidines. Results from the two methods were comparable.", "contents": "GLC determination of quinidines in human plasma. Human plasma was made alkaline and extracted with methylene chloride. To the extract was added the internal standard, cinchonine, followed by evaporation to dryness. The resultant residue was dissolved in a methanolic solution containing trimethylanilinium hydroxide. This solution was assayed by GLC for quinidines (quinidine and hydroquinidine). Evaluation of the method over a 0.5-10-mug/ml range in human plasma gave an overall precision and accuracy of +/- 4.5% (RSD and RE). Plasma of several patients was analyzed by the present method as well as by a fluorometric method for the level of quinidines. Results from the two methods were comparable."} {"id": "PMID:1255442", "title": "Synthesis of histamine analogs.", "content": "Nineteen histamine analogs were synthesized, and their biological actions were compared to those of histamine in blood pressure, gastric secretion, and nasal decongestant screens. The analogs include N-substituted 4-aminoethylimidazoles, N-substituted 2-pyridylethylamines, 2-pyridylcyclohexylamines, and 2-pyridylcyclopropylcarbamates. None of the compounds showed appreciable histamine agonist or antagonist properties.", "contents": "Synthesis of histamine analogs. Nineteen histamine analogs were synthesized, and their biological actions were compared to those of histamine in blood pressure, gastric secretion, and nasal decongestant screens. The analogs include N-substituted 4-aminoethylimidazoles, N-substituted 2-pyridylethylamines, 2-pyridylcyclohexylamines, and 2-pyridylcyclopropylcarbamates. None of the compounds showed appreciable histamine agonist or antagonist properties."} {"id": "PMID:1255443", "title": "NMR analysis of pharmaceuticals XIV: determination of amyl nitrite in its inhalant dosage form.", "content": "An NMR procedure is described for the analysis of amyl nitrite as a drug entity and in inhalant dosage forms. The choices of solvent (carbon tetrachloride) and internal standards (biphenyl or benzyl benzoate) were made with respect to stability problems and the presence of stabilizers in the formulation. The method is precise, with a standard deviation of +/-0.5. The NMR results of synthetic solutions and commercial preparations were compared with those obtained by a published relative NMR procedure and a compendial titrimetric method. The results were generally satisfactory.", "contents": "NMR analysis of pharmaceuticals XIV: determination of amyl nitrite in its inhalant dosage form. An NMR procedure is described for the analysis of amyl nitrite as a drug entity and in inhalant dosage forms. The choices of solvent (carbon tetrachloride) and internal standards (biphenyl or benzyl benzoate) were made with respect to stability problems and the presence of stabilizers in the formulation. The method is precise, with a standard deviation of +/-0.5. The NMR results of synthetic solutions and commercial preparations were compared with those obtained by a published relative NMR procedure and a compendial titrimetric method. The results were generally satisfactory."} {"id": "PMID:1255444", "title": "Solubility of straight-chain and branched alkyl barbiturates in straight-chain alcohols.", "content": "The solubilities of a series of chemically related barbiturates, including some medically useful ones as well as phenobarbital, were determined at 25 degrees in the straight-chain alcohols methanol through butanol. The solubility values are given in both milligrams per milliliter and the mole fraction notation. The solubility in methanol was the highest and decreased nonlinearly for the solubility in 1-butanol. In several cases, mole fraction solubility gave shouldering or peaking as a function of the carbon number of the solvent. This series of barbiturates was broken down into two subsets of straight-chain and branched alkyl barbiturates, and solubility ratios in these subsets were considered.", "contents": "Solubility of straight-chain and branched alkyl barbiturates in straight-chain alcohols. The solubilities of a series of chemically related barbiturates, including some medically useful ones as well as phenobarbital, were determined at 25 degrees in the straight-chain alcohols methanol through butanol. The solubility values are given in both milligrams per milliliter and the mole fraction notation. The solubility in methanol was the highest and decreased nonlinearly for the solubility in 1-butanol. In several cases, mole fraction solubility gave shouldering or peaking as a function of the carbon number of the solvent. This series of barbiturates was broken down into two subsets of straight-chain and branched alkyl barbiturates, and solubility ratios in these subsets were considered."} {"id": "PMID:1255446", "title": "Influence of hydrophobic materials on dissolution of a nondisintegrating hydrophilic solid (potassium chloride).", "content": "A nondisintegrating hydrophilic solid was covered with coatings of hydrophobic materials as a model to study their influence on dissolution rates. Both solution and sublimation techniques were satisfactory for producing coatings of stearic acid. Only a sublimation method was applicable to magnesium stearate, but the resulting coating consisted mainly of a pyrolysis product, stearone. Reductions in dissolution rates in a continuous-flow system could best be interpreted by assuming that they reflected changes in the area of the hydrophilic solid exposed to the solvent. This concept is based on the assumptions that the intrinsic dissolution rate of uncoated potassium chloride did not change and that no dissolution occurred from coated areas. The most important factors controlling the dissolution rate were the strength of attachment of the hydrophobic coat to the surface of the hydrophilic substrate and the thickness of the coat.", "contents": "Influence of hydrophobic materials on dissolution of a nondisintegrating hydrophilic solid (potassium chloride). A nondisintegrating hydrophilic solid was covered with coatings of hydrophobic materials as a model to study their influence on dissolution rates. Both solution and sublimation techniques were satisfactory for producing coatings of stearic acid. Only a sublimation method was applicable to magnesium stearate, but the resulting coating consisted mainly of a pyrolysis product, stearone. Reductions in dissolution rates in a continuous-flow system could best be interpreted by assuming that they reflected changes in the area of the hydrophilic solid exposed to the solvent. This concept is based on the assumptions that the intrinsic dissolution rate of uncoated potassium chloride did not change and that no dissolution occurred from coated areas. The most important factors controlling the dissolution rate were the strength of attachment of the hydrophobic coat to the surface of the hydrophilic substrate and the thickness of the coat."} {"id": "PMID:1255447", "title": "GLC identification and determination of 3,4-methylenedioxyamphetamine (MDA) from plasma and urine.", "content": "A GLC method for qualitative and quantitative determination of 3,4-methylenedioxyamphetamine in biological fluids is described. After extraction of the drug and the internal standard, 4-methoxyamphetamine, from plasma and urine, the solvent is evaporated and the residue is mixed with 20 mul of freshly distilled ether. Aliquots (1-2 mul) then are injected into the gas chromatograph. Both the drug and the internal standard give well-separated symmetrical peaks. Flame-ionization detection allows concentrations of 0.125 mug of 3,4-methylenedioxyamphetamine from plasma to be determined with a precision of 3.16%. The method is applicable to the estimation of 4-methoxyamphetamine, employing 3,4-methylenedioxyamphetamine as the internal standard. For identification purposes, various derivatives such as Schiff bases, isothiocyanates, trifluoroacetates, and heptafluorobutyrates of both compounds were formed following extraction from urine and their GLC behavior was investigated. Derivative formation was confirmed by GLC-mass spectrometry. Mass spectral data for these derivatives are presented.", "contents": "GLC identification and determination of 3,4-methylenedioxyamphetamine (MDA) from plasma and urine. A GLC method for qualitative and quantitative determination of 3,4-methylenedioxyamphetamine in biological fluids is described. After extraction of the drug and the internal standard, 4-methoxyamphetamine, from plasma and urine, the solvent is evaporated and the residue is mixed with 20 mul of freshly distilled ether. Aliquots (1-2 mul) then are injected into the gas chromatograph. Both the drug and the internal standard give well-separated symmetrical peaks. Flame-ionization detection allows concentrations of 0.125 mug of 3,4-methylenedioxyamphetamine from plasma to be determined with a precision of 3.16%. The method is applicable to the estimation of 4-methoxyamphetamine, employing 3,4-methylenedioxyamphetamine as the internal standard. For identification purposes, various derivatives such as Schiff bases, isothiocyanates, trifluoroacetates, and heptafluorobutyrates of both compounds were formed following extraction from urine and their GLC behavior was investigated. Derivative formation was confirmed by GLC-mass spectrometry. Mass spectral data for these derivatives are presented."} {"id": "PMID:1255448", "title": "Quantitative assessment of factors contributing to mottling of colored tablets I: manufacturing variables.", "content": "By using a recently developed method for quantifying the degree of mottling of colored tablets, the effects of manufacturing variables such as the method and temperature of granule drying, granule size, and compaction pressure were investigated. Tablets of dibasic calcium phosphate colored with FD&C Blue No. 1 dye were used. Drying temperature had little effect, but the method of granule drying, granule size, and compaction pressure were major influences on mottling. Mechanisms to explain these results, based on the migration of dye during the drying process, are proposed.", "contents": "Quantitative assessment of factors contributing to mottling of colored tablets I: manufacturing variables. By using a recently developed method for quantifying the degree of mottling of colored tablets, the effects of manufacturing variables such as the method and temperature of granule drying, granule size, and compaction pressure were investigated. Tablets of dibasic calcium phosphate colored with FD&C Blue No. 1 dye were used. Drying temperature had little effect, but the method of granule drying, granule size, and compaction pressure were major influences on mottling. Mechanisms to explain these results, based on the migration of dye during the drying process, are proposed."} {"id": "PMID:1255449", "title": "Quantitative assessment of factors contributing to mottling of colored tablets II: formulation variables.", "content": "The effects of several formulation variables were quantified with respect to factors affecting tablet mottling. Tablet mottling occurred with several commonly used binders and could not be prevented by using highly viscous binding solutions. However, mottling was reduced initially by increasing granule strength. Tablet diluents and dye-adsorbent materials had a profound effect on mottling, not by preventing dye migration but by affecting granule fragmentation on compression and the extent to which the dye-deficient material at the center of the granule was revealed. The lake form of FD&C Blue No. 1 was found to bleed in the presence of diluents that raised the pH of the granulating fluid above 6.4. Anionic impurities in the diluents also caused leaching of free dye and, consequently, increased tablet mottling. The conclusions from this study and previous papers were drawn together to give general principles for the production of uniformly colored tablets by aqueous granulation techniques.", "contents": "Quantitative assessment of factors contributing to mottling of colored tablets II: formulation variables. The effects of several formulation variables were quantified with respect to factors affecting tablet mottling. Tablet mottling occurred with several commonly used binders and could not be prevented by using highly viscous binding solutions. However, mottling was reduced initially by increasing granule strength. Tablet diluents and dye-adsorbent materials had a profound effect on mottling, not by preventing dye migration but by affecting granule fragmentation on compression and the extent to which the dye-deficient material at the center of the granule was revealed. The lake form of FD&C Blue No. 1 was found to bleed in the presence of diluents that raised the pH of the granulating fluid above 6.4. Anionic impurities in the diluents also caused leaching of free dye and, consequently, increased tablet mottling. The conclusions from this study and previous papers were drawn together to give general principles for the production of uniformly colored tablets by aqueous granulation techniques."} {"id": "PMID:1255450", "title": "Constant returns to scale for prescription dispensing in U.S. community pharmacy.", "content": "By using data from a sample of 1767 community pharmacies, a total cost function was estimated by a polynomial regression of total cost on output. The Cobb-Douglas production function was estimated by a multiple linear regression of natural logarithmic transformations of output on natural logarithmic transformation of labor and capital. No economies of scale were found in prescription departments. Cost data led to a conclusion of constant marginal costs.", "contents": "Constant returns to scale for prescription dispensing in U.S. community pharmacy. By using data from a sample of 1767 community pharmacies, a total cost function was estimated by a polynomial regression of total cost on output. The Cobb-Douglas production function was estimated by a multiple linear regression of natural logarithmic transformations of output on natural logarithmic transformation of labor and capital. No economies of scale were found in prescription departments. Cost data led to a conclusion of constant marginal costs."} {"id": "PMID:1255451", "title": "Drug permeation through membranes V: interaction of diazepam with common excipients.", "content": "The effects of common tablet excipients on the permeation of diazepam through polydimethylsiloxane membranes and on the turnover time of goldfish were studied. The permeability coefficient decreased and the turnover time increased in the presence of talc, polysorbate 80, and, possibly, fumed silicon dioxide, but these parameters were unaffected by lactose, microcrystalline cellulose, and starch.", "contents": "Drug permeation through membranes V: interaction of diazepam with common excipients. The effects of common tablet excipients on the permeation of diazepam through polydimethylsiloxane membranes and on the turnover time of goldfish were studied. The permeability coefficient decreased and the turnover time increased in the presence of talc, polysorbate 80, and, possibly, fumed silicon dioxide, but these parameters were unaffected by lactose, microcrystalline cellulose, and starch."} {"id": "PMID:1255452", "title": "Effect of dimethyl sulfoxide on permeability of human skin in vitro.", "content": "A diffusion flow cell is described for the continuous monitoring of skin permeability. The technique was used to study the permeability behavior of human skin subsequent to treatment with dimethyl sulfoxide. Such treatment produced an increased penetration rate of tritiated water, which was dependent upon the time of exposure and the concentration of dimethyl sulfoxide applied. Removal of the solvent resulted in partial recovery of barrier capacity. Skin, incubated in vitro in growth medium containing dimethyl sulfoxide, survived only at very low concentrations. Degeneration occurred after a few days in 4.5% dimethyl sulfoxide and much sooner at higher concentrations.", "contents": "Effect of dimethyl sulfoxide on permeability of human skin in vitro. A diffusion flow cell is described for the continuous monitoring of skin permeability. The technique was used to study the permeability behavior of human skin subsequent to treatment with dimethyl sulfoxide. Such treatment produced an increased penetration rate of tritiated water, which was dependent upon the time of exposure and the concentration of dimethyl sulfoxide applied. Removal of the solvent resulted in partial recovery of barrier capacity. Skin, incubated in vitro in growth medium containing dimethyl sulfoxide, survived only at very low concentrations. Degeneration occurred after a few days in 4.5% dimethyl sulfoxide and much sooner at higher concentrations."} {"id": "PMID:1255453", "title": "Evaluation of emulsion stability by diffuse reflectance spectroscopy.", "content": "A new method is described for evaluating the stability of emulsion bases and active components contained within such emulsions. Diffuse reflectance spectroscopy (DRS) is a technique that has the capability of detecting changes in particle size, surface properties, or drug quality of emulsions as a function of time without disturbance of the system. Such physical or chemical changes are monitored by changes in the visible and UV wavelength spectral characteristics of the emulsified systems. Four basic emulsion systems were prepared and analyzed for physical stability for 6 months by three techniques: visible coalescence, particle counting measurement, and DRS. Two drugs, aspirin and ascorbic acid, were then incorporated within stable emulsion bases, and the chemical stability of these drugs was monitored by DRS for 6 months. Results were compared with concomitant quantitative drug assay procedures. Good agreement was observed when data from DRS and analytical measurements were compared. The DRS technique may be used as a supportive method, offering simplicity and expedience, with other methods of evaluating emulsion stability and drug stability within emulsified systems.", "contents": "Evaluation of emulsion stability by diffuse reflectance spectroscopy. A new method is described for evaluating the stability of emulsion bases and active components contained within such emulsions. Diffuse reflectance spectroscopy (DRS) is a technique that has the capability of detecting changes in particle size, surface properties, or drug quality of emulsions as a function of time without disturbance of the system. Such physical or chemical changes are monitored by changes in the visible and UV wavelength spectral characteristics of the emulsified systems. Four basic emulsion systems were prepared and analyzed for physical stability for 6 months by three techniques: visible coalescence, particle counting measurement, and DRS. Two drugs, aspirin and ascorbic acid, were then incorporated within stable emulsion bases, and the chemical stability of these drugs was monitored by DRS for 6 months. Results were compared with concomitant quantitative drug assay procedures. Good agreement was observed when data from DRS and analytical measurements were compared. The DRS technique may be used as a supportive method, offering simplicity and expedience, with other methods of evaluating emulsion stability and drug stability within emulsified systems."} {"id": "PMID:1255454", "title": "IR studies of development of order in aluminum hydroxide gels.", "content": "The usefulness of deuteration in detecting the development of order in aluminum hydroxide gel by IR spectra is demonstrated. By treatment of gel samples with deuterium oxide vapor at room temperature, the relative ease with which deuteroxyl-hydroxyl exchange takes place is determined as a function of the age of the gel. The use of scale expansion in conjunction with deuteration allows detection of IR absorbance characteristic of gibbsitic material long before such detection is possible by conventional IR analysis or X-ray diffraction.", "contents": "IR studies of development of order in aluminum hydroxide gels. The usefulness of deuteration in detecting the development of order in aluminum hydroxide gel by IR spectra is demonstrated. By treatment of gel samples with deuterium oxide vapor at room temperature, the relative ease with which deuteroxyl-hydroxyl exchange takes place is determined as a function of the age of the gel. The use of scale expansion in conjunction with deuteration allows detection of IR absorbance characteristic of gibbsitic material long before such detection is possible by conventional IR analysis or X-ray diffraction."} {"id": "PMID:1255455", "title": "Utilization of an enantiomer as a solution to a pharmaceutical problem: application to solubilization of 1,2-di(4-piperazine-2,6-dione)propane.", "content": "An enantiomer of the cytotoxic agent (+/-)-1,2-di(4-piperazine-2,6-dione)propane [(+/-)-I] (ICRF 159) was utilized to overcome a solubility problem in the preparation of a solution suitable for intravenous use. The enantiomers were about five times more soluble and melted at about 40 degrees lower than the racemic compound. This study appears to be the first reported instance in which the difference in the physical properties of a racemic compound and its enantiomers was utilized to improve a pharmaceutical formulation. The expected differences in the physical properties of racemic solids and their corresponding enantiomers are discussed briefly in relation to the three racemic modifications known to exist.", "contents": "Utilization of an enantiomer as a solution to a pharmaceutical problem: application to solubilization of 1,2-di(4-piperazine-2,6-dione)propane. An enantiomer of the cytotoxic agent (+/-)-1,2-di(4-piperazine-2,6-dione)propane [(+/-)-I] (ICRF 159) was utilized to overcome a solubility problem in the preparation of a solution suitable for intravenous use. The enantiomers were about five times more soluble and melted at about 40 degrees lower than the racemic compound. This study appears to be the first reported instance in which the difference in the physical properties of a racemic compound and its enantiomers was utilized to improve a pharmaceutical formulation. The expected differences in the physical properties of racemic solids and their corresponding enantiomers are discussed briefly in relation to the three racemic modifications known to exist."} {"id": "PMID:1255456", "title": "Limitations in interpretation of digoxin adsorption using averaged pharmacological response intensities.", "content": "In this paper, the interpretation of averaged pharmacological effect data for the cardiac glycoside digoxin is reconsidered through a comparison with theoretically simulated data. Four parameters, with their standard deviations calculated from the best-fit biexponential equation for the experimentally derived transformed pharmacological response intensity, were the basis for the random development of a series of 17 individual sets of data with average parameters and standard deviations identical to the values found experimentally. Parameters from these 17 data sets were averaged and randomly altered as a function of the standard deviations for each average. Loo-Riegelman analyses, modified for application to the peripheral compartment, and fraction remaining to be absorbed plots were made. Results of this comparison of experimental pharmacological simulated data indicate that the presence or absence of enterohepatic recycling may not be unambiguously determined here.", "contents": "Limitations in interpretation of digoxin adsorption using averaged pharmacological response intensities. In this paper, the interpretation of averaged pharmacological effect data for the cardiac glycoside digoxin is reconsidered through a comparison with theoretically simulated data. Four parameters, with their standard deviations calculated from the best-fit biexponential equation for the experimentally derived transformed pharmacological response intensity, were the basis for the random development of a series of 17 individual sets of data with average parameters and standard deviations identical to the values found experimentally. Parameters from these 17 data sets were averaged and randomly altered as a function of the standard deviations for each average. Loo-Riegelman analyses, modified for application to the peripheral compartment, and fraction remaining to be absorbed plots were made. Results of this comparison of experimental pharmacological simulated data indicate that the presence or absence of enterohepatic recycling may not be unambiguously determined here."} {"id": "PMID:1255457", "title": "Anaerobic photodecomposition of an acridan drug through energy transfer.", "content": "Anaerobic irradiation of 2-chloro-9-(3-dimethylaminopropyl)acridan phosphate (1:1) (IIIa) with filtered visible light (300-400 nm) resulted in its quantitative conversion to its acridine derivative IV. Photoproduct IV exerted significant product catalysis on the reaction rate at concentrations of 5 x 10(-6) M. The anaerobic photodecomposition of IIIa to IV was catalyzed by the monosodium salt of riboflavin 5-phosphate (Ia). Loss of Ia was insignificant relative to that of IIIa, and reagents known to serve as quenchers of the triplet state of Ia retarded the reaction. Fluorescence spectra of Ia in the presence of IIIa and 1 x 10(-4) M KI indicated no quenching of the Ia singlet excited state. No deuterium isotope effect was noticed when IIIa and its deuterated derivative IIIb were subjected to anaerobic photodecomposition in the presence of Ia. It is suggested that the anaerobic photodecomposition of IIIa by visible light in the presence of Ia proceeds via a triplet-triplet energy transfer from Ia to IIIa.", "contents": "Anaerobic photodecomposition of an acridan drug through energy transfer. Anaerobic irradiation of 2-chloro-9-(3-dimethylaminopropyl)acridan phosphate (1:1) (IIIa) with filtered visible light (300-400 nm) resulted in its quantitative conversion to its acridine derivative IV. Photoproduct IV exerted significant product catalysis on the reaction rate at concentrations of 5 x 10(-6) M. The anaerobic photodecomposition of IIIa to IV was catalyzed by the monosodium salt of riboflavin 5-phosphate (Ia). Loss of Ia was insignificant relative to that of IIIa, and reagents known to serve as quenchers of the triplet state of Ia retarded the reaction. Fluorescence spectra of Ia in the presence of IIIa and 1 x 10(-4) M KI indicated no quenching of the Ia singlet excited state. No deuterium isotope effect was noticed when IIIa and its deuterated derivative IIIb were subjected to anaerobic photodecomposition in the presence of Ia. It is suggested that the anaerobic photodecomposition of IIIa by visible light in the presence of Ia proceeds via a triplet-triplet energy transfer from Ia to IIIa."} {"id": "PMID:1255458", "title": "Solution thermodynamics of alkyl p-aminobenzoates.", "content": "Equilibrium solubilities of the first four homologous alkyl p-aminobenzoate esters were determined in methanol, ethanol, and 1-propanol at 25, 33, and 40 degrees; the esters and the alcohols comprise separate homologous series. The solution process of a solute may be considered to be the summation of two sequential steps, melting and mixing, and the magnitude of solubility depends upon temperature and the extent of interactions between solute and solvent molecules. Quantitative solute concentrations, obtained from spectrophotometric analysis, were converted to mole fractions. Statistical analysis of the logarithmic mole fraction solubilities of the aminobenzoates, which were linear with respect to both reciprocal absolute temperature and the logarithm of absolute temperature, generated enthalpies and entropies of solution, respectively. The heats of fusion and the melting points of these aminobenzoates were determined to calculate their ideal solubilities. Excess free energies and partial molal free energies of each solution were calculated from the activity coefficients of the solutes; the thermodynamic elements for these systems are discussed.", "contents": "Solution thermodynamics of alkyl p-aminobenzoates. Equilibrium solubilities of the first four homologous alkyl p-aminobenzoate esters were determined in methanol, ethanol, and 1-propanol at 25, 33, and 40 degrees; the esters and the alcohols comprise separate homologous series. The solution process of a solute may be considered to be the summation of two sequential steps, melting and mixing, and the magnitude of solubility depends upon temperature and the extent of interactions between solute and solvent molecules. Quantitative solute concentrations, obtained from spectrophotometric analysis, were converted to mole fractions. Statistical analysis of the logarithmic mole fraction solubilities of the aminobenzoates, which were linear with respect to both reciprocal absolute temperature and the logarithm of absolute temperature, generated enthalpies and entropies of solution, respectively. The heats of fusion and the melting points of these aminobenzoates were determined to calculate their ideal solubilities. Excess free energies and partial molal free energies of each solution were calculated from the activity coefficients of the solutes; the thermodynamic elements for these systems are discussed."} {"id": "PMID:1255459", "title": "Simultaneous determination of pilocarpine and isopilocarpine in pharmaceutical preparations by liquid chromatography.", "content": "A liquid chromatographic assay method is described for the simultaneous determination of pilocarpine and isopilocarpine in pharmaceutical preparations. The method involves separation of the isomers on a high-resolution ion-exchange column, followed by detection of pilocarpine and isopilocarpine by UV absorption in the 217-nm region. The specificity of the method is such that pilocarpine and isopilocarpine can be assayed separately in the presence of one another and in the presence of the excipients commonly found in commercial pilocarpine solutions. Its sensitivity for isopilocarpine is at least 25 ppm (independent of the concentration of pilocarpine). In contrast, USP methods lack both specificity and sensitivity. It is concluded that this method is applicable to the routine analysis of commercial pilocarpine preparations and is an improvement over the official methods.", "contents": "Simultaneous determination of pilocarpine and isopilocarpine in pharmaceutical preparations by liquid chromatography. A liquid chromatographic assay method is described for the simultaneous determination of pilocarpine and isopilocarpine in pharmaceutical preparations. The method involves separation of the isomers on a high-resolution ion-exchange column, followed by detection of pilocarpine and isopilocarpine by UV absorption in the 217-nm region. The specificity of the method is such that pilocarpine and isopilocarpine can be assayed separately in the presence of one another and in the presence of the excipients commonly found in commercial pilocarpine solutions. Its sensitivity for isopilocarpine is at least 25 ppm (independent of the concentration of pilocarpine). In contrast, USP methods lack both specificity and sensitivity. It is concluded that this method is applicable to the routine analysis of commercial pilocarpine preparations and is an improvement over the official methods."} {"id": "PMID:1255460", "title": "Electron beam ionization mass fragmentographic analysis of tricyclic antidepressants in human plasma.", "content": "A method for the measurement, in human plasma, of all tertiary and secondary tricyclic antidepressants prescribed in the United States is described. The method uses electron beam ionization GLC-mass spectrometry, employing a computer-controlled multiple-ion detector. This method, mass fragmentography, is used with internal standards for each drug. Plasma levels to as low as 10 ng/ml of the following drugs can be measured: amitriptyline, nortriptyline, doxepin, desmethyldoxepin, imipramine, desipramine, and protriptyline. Deuterium-labeled amitriptyline and imipramine are used as internal standards for those two drugs; for the other drugs, deuterated amitriptyline, nortriptyline, desmethyldoxepin, or desipramine is used. The method can measure up to 15 samples/hr, making it practical for large-scale studies of these drugs in patients. Spectra of each drug and examples of their analysis are given.", "contents": "Electron beam ionization mass fragmentographic analysis of tricyclic antidepressants in human plasma. A method for the measurement, in human plasma, of all tertiary and secondary tricyclic antidepressants prescribed in the United States is described. The method uses electron beam ionization GLC-mass spectrometry, employing a computer-controlled multiple-ion detector. This method, mass fragmentography, is used with internal standards for each drug. Plasma levels to as low as 10 ng/ml of the following drugs can be measured: amitriptyline, nortriptyline, doxepin, desmethyldoxepin, imipramine, desipramine, and protriptyline. Deuterium-labeled amitriptyline and imipramine are used as internal standards for those two drugs; for the other drugs, deuterated amitriptyline, nortriptyline, desmethyldoxepin, or desipramine is used. The method can measure up to 15 samples/hr, making it practical for large-scale studies of these drugs in patients. Spectra of each drug and examples of their analysis are given."} {"id": "PMID:1255461", "title": "Isomeric inversion of ibuprofen (R)-enantiomer in humans.", "content": "Enantiomeric compositions of the major urinary metabolites of ibuprofen [(RS)-2-(4-isobutylphenyl)propionic acid]were characterized after oral administration of the racemic mixture and oral administration of the individual enantiomers to normal human volunteers. Resolution of the diastereomeric amides, formed by reaction of the urinary metabolites with (S)-(-)-alpha-methylbenzylamine, was achieved by GLC. Only the (R)-(-)-enantiomer of the intact drug was inverted to its optical antipode, (S)-(+), in humans. However, both (S)-(+)- and (R)-(-)-enantiomers of the intact drug were transformed independently in vivo to the major metabolites, i.e., 2,4'-(2-hydroxy-2-methylpropyl)phenylpropionic acid and 2,4'-(2-carboxypropyl)phenylpropionic acid. In vivo metabolism of ibuprofen to its carboxy metabolite was not stereoselective.", "contents": "Isomeric inversion of ibuprofen (R)-enantiomer in humans. Enantiomeric compositions of the major urinary metabolites of ibuprofen [(RS)-2-(4-isobutylphenyl)propionic acid]were characterized after oral administration of the racemic mixture and oral administration of the individual enantiomers to normal human volunteers. Resolution of the diastereomeric amides, formed by reaction of the urinary metabolites with (S)-(-)-alpha-methylbenzylamine, was achieved by GLC. Only the (R)-(-)-enantiomer of the intact drug was inverted to its optical antipode, (S)-(+), in humans. However, both (S)-(+)- and (R)-(-)-enantiomers of the intact drug were transformed independently in vivo to the major metabolites, i.e., 2,4'-(2-hydroxy-2-methylpropyl)phenylpropionic acid and 2,4'-(2-carboxypropyl)phenylpropionic acid. In vivo metabolism of ibuprofen to its carboxy metabolite was not stereoselective."} {"id": "PMID:1255462", "title": "Determination of methyl methacrylate in surgical acrylic cement.", "content": "A methyl methacrylate cement used in hip surgery as well as in dentistry was identified and quantitatively analyzed for its monomer content in starting materials and in the finished cement by proton magnetic resonance spectroscopy. IR data indicated that the monomer continued to escape from the product after it had hardened. The presence of 21% methyl methacrylate monomer relative to the polymer was demonstrated at the time the cement normally would be inserted into the body.", "contents": "Determination of methyl methacrylate in surgical acrylic cement. A methyl methacrylate cement used in hip surgery as well as in dentistry was identified and quantitatively analyzed for its monomer content in starting materials and in the finished cement by proton magnetic resonance spectroscopy. IR data indicated that the monomer continued to escape from the product after it had hardened. The presence of 21% methyl methacrylate monomer relative to the polymer was demonstrated at the time the cement normally would be inserted into the body."} {"id": "PMID:1255463", "title": "Tumor inhibitors II: constituents and antitumor activity of Sarracenia flava.", "content": "The chloroform extracts of the roots and leaves of Sarracenia flava showed antitumor activity against lymphocytic leukemia P-388. Lupeol was identified as one constituent responsible for this activity. Beta-Sitosterol and alpha-amyrin were isolated from the hexane extract of the roots.", "contents": "Tumor inhibitors II: constituents and antitumor activity of Sarracenia flava. The chloroform extracts of the roots and leaves of Sarracenia flava showed antitumor activity against lymphocytic leukemia P-388. Lupeol was identified as one constituent responsible for this activity. Beta-Sitosterol and alpha-amyrin were isolated from the hexane extract of the roots."} {"id": "PMID:1255464", "title": "Potential organ or tumor imaging agents XV: radioiodinated phenytoin derivatives.", "content": "Three radioiodinated phenytoin analogs were synthesized, and tissue distribution studies were conducted in rats. Except for a greater retention of radioactivity following administration of the radioiodinated derivatives, the tissue distribution patterns were qualitatively similar to those found for 14C phenytoin. In nearly all cases, the adrenals, heart, kidneys, and liver displayed the greatest capacity to retain radioactivity. The high uptake of radioactivity observed for the thyroid was attributed to in vivo metabolic deiodination of the radioiodinated derivatives.", "contents": "Potential organ or tumor imaging agents XV: radioiodinated phenytoin derivatives. Three radioiodinated phenytoin analogs were synthesized, and tissue distribution studies were conducted in rats. Except for a greater retention of radioactivity following administration of the radioiodinated derivatives, the tissue distribution patterns were qualitatively similar to those found for 14C phenytoin. In nearly all cases, the adrenals, heart, kidneys, and liver displayed the greatest capacity to retain radioactivity. The high uptake of radioactivity observed for the thyroid was attributed to in vivo metabolic deiodination of the radioiodinated derivatives."} {"id": "PMID:1255465", "title": "Permethylation of barbiturates: variation in product ratios with varying methylsulfinylmethide carbanion.", "content": "Permethylation of a barbiturate with the methylsulfinylmethide carbanion and methyl iodide gave three products clearly separable by GLC. Alteration of the reaction conditions by varying the barbiturate to carbanion ratio or the barbiturate to carbanion exposure time resulted in a single product for only one examined barbiturate, secobarbital. This derivatization technique is useful for the GLC analysis of polar barbiturate metabolites, such as glucuronides, in biological fluids but is of limited value for the analysis of the parent compounds.", "contents": "Permethylation of barbiturates: variation in product ratios with varying methylsulfinylmethide carbanion. Permethylation of a barbiturate with the methylsulfinylmethide carbanion and methyl iodide gave three products clearly separable by GLC. Alteration of the reaction conditions by varying the barbiturate to carbanion ratio or the barbiturate to carbanion exposure time resulted in a single product for only one examined barbiturate, secobarbital. This derivatization technique is useful for the GLC analysis of polar barbiturate metabolites, such as glucuronides, in biological fluids but is of limited value for the analysis of the parent compounds."} {"id": "PMID:1255466", "title": "Synthesis of 2'-acetoxybiphenyl-2-carboxylic acid and its derivatives as potential anti-inflammatory and analgesic agents.", "content": "2'-Acetoxybiphenyl-2-carboxylic acid and a series of derivatives were synthesized. The title compound and its unsubstituted amide had both anti-inflammatory and analgesic properties. Its aminoethyl esters exhibited only analgesia. None of the compounds showed any significant antimicrobial activity.", "contents": "Synthesis of 2'-acetoxybiphenyl-2-carboxylic acid and its derivatives as potential anti-inflammatory and analgesic agents. 2'-Acetoxybiphenyl-2-carboxylic acid and a series of derivatives were synthesized. The title compound and its unsubstituted amide had both anti-inflammatory and analgesic properties. Its aminoethyl esters exhibited only analgesia. None of the compounds showed any significant antimicrobial activity."} {"id": "PMID:1255467", "title": "Isolation and chemistry of alkaloids from plants of the family Papaveraceae LXVII: Corydalis cava (L.) Sch. et K. (C. tuberosa DC).", "content": "From Corydalis cava (L.) Sch. et K. (C. tuberosa DC) (Papaveraceae: genus Corydalis Med.), a mixture of alkaloids (0.53%) was isolated. The main alkaloid was (+)-bulbocapnine, and the minor alkaloids were coptisine, (+)-domestine, adlumidiceine, (+)-predicentrine, protopine, (-)-capnoidine, (+)-stylopine, (+)-isoboldine, 8-oxocoptisine, 1,2-methylenedioxy-6a,7-dehydroaporphine-10,11-quinone, and corysamine. In addition, fumaric acid was obtained. Coptisine, adlumidiceine, predicentrine, 8-oxocoptisine, corysamine, 1,2-methylenedioxy-6a, 7-dehydroaporphine-10,11-quinone, and isoboldine were found in C. cava for the first time, but rhoeadine and papaverrubine alkaloids were not detected. Predicentrine and isoboldine were identified on the basis of the UV, IR, mass, and PMR spectra.", "contents": "Isolation and chemistry of alkaloids from plants of the family Papaveraceae LXVII: Corydalis cava (L.) Sch. et K. (C. tuberosa DC). From Corydalis cava (L.) Sch. et K. (C. tuberosa DC) (Papaveraceae: genus Corydalis Med.), a mixture of alkaloids (0.53%) was isolated. The main alkaloid was (+)-bulbocapnine, and the minor alkaloids were coptisine, (+)-domestine, adlumidiceine, (+)-predicentrine, protopine, (-)-capnoidine, (+)-stylopine, (+)-isoboldine, 8-oxocoptisine, 1,2-methylenedioxy-6a,7-dehydroaporphine-10,11-quinone, and corysamine. In addition, fumaric acid was obtained. Coptisine, adlumidiceine, predicentrine, 8-oxocoptisine, corysamine, 1,2-methylenedioxy-6a, 7-dehydroaporphine-10,11-quinone, and isoboldine were found in C. cava for the first time, but rhoeadine and papaverrubine alkaloids were not detected. Predicentrine and isoboldine were identified on the basis of the UV, IR, mass, and PMR spectra."} {"id": "PMID:1255468", "title": "Synthesis of site-directed chelating agents II: 2-formyl-3-hydroxy-4,5-bis (hydroxymethyl)pyridine thiosemicarbazone.", "content": "2-Formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was synthesized in an attempt to direct the chelating potential of this agent to the active site of the zinc-requiring enzyme pyridoxal phosphokinase. Evaluation of the antineoplastic activity of this agent in the sarcoma 180 and L-1210 leukemia systems in mice showed potent activity. The presence or absence of pyridoxine hydrochloride in the diet did not influence the degree of inhibition of the growth of sarcoma 180 ascites cells. In addition, 2-formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was inactive against a subline of sarcoma 180 resistant to 1-formylisoquinoline thiosemicarbazone, suggesting that the former agent may have a biochemical mechanism of action similar to that of the latter. In keeping with this expectation, 2-formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone inhibited the synthesis of DNA but not of RNA or protein in sarcoma 180 ascites cells in vitro.", "contents": "Synthesis of site-directed chelating agents II: 2-formyl-3-hydroxy-4,5-bis (hydroxymethyl)pyridine thiosemicarbazone. 2-Formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was synthesized in an attempt to direct the chelating potential of this agent to the active site of the zinc-requiring enzyme pyridoxal phosphokinase. Evaluation of the antineoplastic activity of this agent in the sarcoma 180 and L-1210 leukemia systems in mice showed potent activity. The presence or absence of pyridoxine hydrochloride in the diet did not influence the degree of inhibition of the growth of sarcoma 180 ascites cells. In addition, 2-formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone was inactive against a subline of sarcoma 180 resistant to 1-formylisoquinoline thiosemicarbazone, suggesting that the former agent may have a biochemical mechanism of action similar to that of the latter. In keeping with this expectation, 2-formyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine thiosemicarbazone inhibited the synthesis of DNA but not of RNA or protein in sarcoma 180 ascites cells in vitro."} {"id": "PMID:1255469", "title": "N-bromosuccinimide assay of penicillins and cephalosporins.", "content": "All penicillins and cephalosporins known to possess biological activity respond to an N-bromosuccinimide assay. The developed method is not yet usable for determining stability, but it is useful as a bulk or batching assay.", "contents": "N-bromosuccinimide assay of penicillins and cephalosporins. All penicillins and cephalosporins known to possess biological activity respond to an N-bromosuccinimide assay. The developed method is not yet usable for determining stability, but it is useful as a bulk or batching assay."} {"id": "PMID:1255470", "title": "Effect of polyethylene glycol 4000 on dissolution properties of sulfathiazole polymorphs.", "content": "The dissolution rates of the two polymorphic forms of sulfathiazole containing polyethylene glycol 4000 were significantly different in water. The effect of agitation on the dissolution rates also was studied. At higher stirring speeds, the dissolution rates of the stable form were affected more than the metastable form. A high concentration of polyethylene glycol 4000 seemed to affect the dissolution properties of the metastable polymorph more than the stable polymorph.", "contents": "Effect of polyethylene glycol 4000 on dissolution properties of sulfathiazole polymorphs. The dissolution rates of the two polymorphic forms of sulfathiazole containing polyethylene glycol 4000 were significantly different in water. The effect of agitation on the dissolution rates also was studied. At higher stirring speeds, the dissolution rates of the stable form were affected more than the metastable form. A high concentration of polyethylene glycol 4000 seemed to affect the dissolution properties of the metastable polymorph more than the stable polymorph."} {"id": "PMID:1255471", "title": "Selenium heterocycles XVIII: Synthesis and antibacterial activity of 4-substituted (1,2,3-selenadiazol-5-yl) carbamic acid esters and their sulfur analogs.", "content": "4-Substituted (1,2,3-selenadiazol-5-yl)carbamic acid esters and their sulfur analogs were prepared from the Curtius rearrangement of the corresponding carboxazides. None of the compounds showed significant antibacterial activity.", "contents": "Selenium heterocycles XVIII: Synthesis and antibacterial activity of 4-substituted (1,2,3-selenadiazol-5-yl) carbamic acid esters and their sulfur analogs. 4-Substituted (1,2,3-selenadiazol-5-yl)carbamic acid esters and their sulfur analogs were prepared from the Curtius rearrangement of the corresponding carboxazides. None of the compounds showed significant antibacterial activity."} {"id": "PMID:1255475", "title": "Urinary excretion of heroin and its metabolites in man.", "content": "The purpose of this study was to investigate the kinetics of urinary excretion of heroin and its metabolites in human subjects. Heroin and its metabolites were determined with gas-liquid chromatography. Two studies were conducted, each using 10 subjects. After i.v. administration of heroin HC1, 10 mg/70 kg, urine was collected every 8 hours and ad libitum for 1 week in the first study and every 2 hours in the first 8 hours and then at less frequent intervals for 24 hours in the second study. Heroin, 6-acetylmorphine, morphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were determined in the first 24-hour urine and accounted for 0.5, 1.5, 7.2, 52 and 4%, respectively, of the administered dose. Conjugated morphine could be detected in the urine 96 hours after drug administration. Eighty-eight percent of the free morphine and 84% of the total morphine found in the urine were excreted in the first 8 hours. The half-lives of urinary excretion of free morphine, 6-acetylmorphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were 1.28, 1.31, 2.76 and 2.72 hours, respectively. It was concluded that heroin in the body was rapidly metabolized and its metabolites were rapidly excreted in the urine.", "contents": "Urinary excretion of heroin and its metabolites in man. The purpose of this study was to investigate the kinetics of urinary excretion of heroin and its metabolites in human subjects. Heroin and its metabolites were determined with gas-liquid chromatography. Two studies were conducted, each using 10 subjects. After i.v. administration of heroin HC1, 10 mg/70 kg, urine was collected every 8 hours and ad libitum for 1 week in the first study and every 2 hours in the first 8 hours and then at less frequent intervals for 24 hours in the second study. Heroin, 6-acetylmorphine, morphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were determined in the first 24-hour urine and accounted for 0.5, 1.5, 7.2, 52 and 4%, respectively, of the administered dose. Conjugated morphine could be detected in the urine 96 hours after drug administration. Eighty-eight percent of the free morphine and 84% of the total morphine found in the urine were excreted in the first 8 hours. The half-lives of urinary excretion of free morphine, 6-acetylmorphine, the sum of conjugates (morphine plus 6-acetylmorphine) and total normorphine were 1.28, 1.31, 2.76 and 2.72 hours, respectively. It was concluded that heroin in the body was rapidly metabolized and its metabolites were rapidly excreted in the urine."} {"id": "PMID:1255476", "title": "Physiological disposition and biotransformation of [allyl-1', 3' - 14C naloxone in the rat and some comparative observations on nalorphine.", "content": "A sensitive method is described for the estimation of [14C]naloxone in biological materials. After a 1 mg/kg s.c. dose of [14C]naloxone to male Wistar rats, mean peak levels of drug in brain (506 ng/g) and plasma (119 ng/ml) were attained within 15 minutes. No persistence of drug in brain was observed at this dose. After a 10 mg/kg s.c. dose, the peak levels of naloxone in brain and plasma were 4.31 mug/g and 1.27 mug/ml, respectively, and extensive localization of extractable free drug and its minor metabolite, naloxol, occurred in tissues with high levels in kidney, spleen, lung, heart, skeletal muscle and somewhat lower concentration in the liver. The T1/2 of naloxone and nalorphine in rat brain and plasma with 1 and 10 mg/kg s.c. doses was 0.4 hour. With a 10 mg/kg dose, significant amounts of radioactivity persisted in tissues but not in plasma 96 hours after injection. The brain/plasma ratios and degree of plasma-protein binding were significantly higher for naloxone as compared to nalorphine. The amounts of free naloxone excreted as a percentage of the dose in urine and feces 96 hours after injection of the 10 mg/kg s.c. dose were 4.1 and 3.9 (for nalorphine 4.7 and 8.3); conjugated drug 15.4 and 1.2 (for nalorphine 13 and 0.9); total radioactivity 43.3 and 20.9 (for nalorphine 34.8 and 19.2), respectively. Naloxone-3-glucuronide (major), 3-sulfate (minor), naloxol and conjugated naloxol (minor), 7,8-dihydro-14-hydroxynormorphine, 7,8-dihydro-14-hydroxynormorphine and their conjugates were shown to be the metabolites of naloxone. In addition, tentative evidence was obtained for two polar hydroxylated metabolites (with hydroxylation presumably in the 17-side chain or in position 2 of the aromatic nucleus). 7,8-Dihydro-14-hydroxynormorphinone and 2-polar metabolites were also observed in brain. Rapid metabolism of naloxone and rapid elimination are important factors in its short duration of action. Possible relevance of these observations on differential antagonistic properties of these two antagonists are discussed.", "contents": "Physiological disposition and biotransformation of [allyl-1', 3' - 14C naloxone in the rat and some comparative observations on nalorphine. A sensitive method is described for the estimation of [14C]naloxone in biological materials. After a 1 mg/kg s.c. dose of [14C]naloxone to male Wistar rats, mean peak levels of drug in brain (506 ng/g) and plasma (119 ng/ml) were attained within 15 minutes. No persistence of drug in brain was observed at this dose. After a 10 mg/kg s.c. dose, the peak levels of naloxone in brain and plasma were 4.31 mug/g and 1.27 mug/ml, respectively, and extensive localization of extractable free drug and its minor metabolite, naloxol, occurred in tissues with high levels in kidney, spleen, lung, heart, skeletal muscle and somewhat lower concentration in the liver. The T1/2 of naloxone and nalorphine in rat brain and plasma with 1 and 10 mg/kg s.c. doses was 0.4 hour. With a 10 mg/kg dose, significant amounts of radioactivity persisted in tissues but not in plasma 96 hours after injection. The brain/plasma ratios and degree of plasma-protein binding were significantly higher for naloxone as compared to nalorphine. The amounts of free naloxone excreted as a percentage of the dose in urine and feces 96 hours after injection of the 10 mg/kg s.c. dose were 4.1 and 3.9 (for nalorphine 4.7 and 8.3); conjugated drug 15.4 and 1.2 (for nalorphine 13 and 0.9); total radioactivity 43.3 and 20.9 (for nalorphine 34.8 and 19.2), respectively. Naloxone-3-glucuronide (major), 3-sulfate (minor), naloxol and conjugated naloxol (minor), 7,8-dihydro-14-hydroxynormorphine, 7,8-dihydro-14-hydroxynormorphine and their conjugates were shown to be the metabolites of naloxone. In addition, tentative evidence was obtained for two polar hydroxylated metabolites (with hydroxylation presumably in the 17-side chain or in position 2 of the aromatic nucleus). 7,8-Dihydro-14-hydroxynormorphinone and 2-polar metabolites were also observed in brain. Rapid metabolism of naloxone and rapid elimination are important factors in its short duration of action. Possible relevance of these observations on differential antagonistic properties of these two antagonists are discussed."} {"id": "PMID:1255477", "title": "Studies on tolerance. I. The role of the interval between doses on the development of tolerance to morphine.", "content": "The effect of varying the interval between doses on the rate of development of tolerance to a series of injections of morphine was studied in two strains of rats. Morphine sulfate injections (15 mg/kg s.c.) were given at intervals of 1, 2, 3, 7, 10, 14 or 21 days to adult male Wistar/Furth or Wistar-Lewis rats and drug effect was measured by means of the hot-plate assay technique. A diminution of morphine effect on the second or subsequent injections of drug was considered to be the result of the development of tolerance. Little or no tolerance was observed with the Wistar/Furth animals when a second injection or morphine was administered 7 days after the first, although there was marked tolerance when there were shorter or longer intervals between the first two injections. Subsequent injections of morphine sulfate, given to the animals at the predetermined intervals, resulted in wiping out out the differences between all interval groups, with the exception of the 1-day group, by the fifth injection. Although the differences between the 7-day and longer or shorter intervals were not as great with the Wistar-Lewis animals, they were significant and may reflect a slightly different rate of tolerance development in the latter strain. These observations are consistent with the hypothesis that there may be two types of tolerance, one appearing very rapidly, the other taking a longer period of time to develop.", "contents": "Studies on tolerance. I. The role of the interval between doses on the development of tolerance to morphine. The effect of varying the interval between doses on the rate of development of tolerance to a series of injections of morphine was studied in two strains of rats. Morphine sulfate injections (15 mg/kg s.c.) were given at intervals of 1, 2, 3, 7, 10, 14 or 21 days to adult male Wistar/Furth or Wistar-Lewis rats and drug effect was measured by means of the hot-plate assay technique. A diminution of morphine effect on the second or subsequent injections of drug was considered to be the result of the development of tolerance. Little or no tolerance was observed with the Wistar/Furth animals when a second injection or morphine was administered 7 days after the first, although there was marked tolerance when there were shorter or longer intervals between the first two injections. Subsequent injections of morphine sulfate, given to the animals at the predetermined intervals, resulted in wiping out out the differences between all interval groups, with the exception of the 1-day group, by the fifth injection. Although the differences between the 7-day and longer or shorter intervals were not as great with the Wistar-Lewis animals, they were significant and may reflect a slightly different rate of tolerance development in the latter strain. These observations are consistent with the hypothesis that there may be two types of tolerance, one appearing very rapidly, the other taking a longer period of time to develop."} {"id": "PMID:1255478", "title": "Behavioral effects of L-5-hydroxytryptophan after destruction of ascending serotonergic pathways in the rat: the role of catecholaminergic neurons.", "content": "Lesions in the medial forebrain bundle of the rat produced a 68 to 74% decrease in telencephalic serotonin (5-HT) and a 30 to 43% decrease in jump threshold. L-5-Hydroxytryptophan (L-5-HTP; 37.5 mg/kg) returned the 5-HT content and jump threshold of lesioned rats to normal levels. These effects of L-5-HTP were also observed after the inhibition of extracerebral decarboxylase activity with Ro 4-4602 (50 mg/kg). Pretreatment with 6-hydroxydopamine (6-OHDA), which selectively destroys catecholamine neurons, had no effect on the jump threshold of nonlesioned rats nor did it further change the 5-HT content or jump threshold of lesioned rats. Lesioned rats pretreated with 6-OHDA demonstrated an increase in 5-HT content after L-5-HTP; however, their jump threshold remained significantly lower than that of controls. This ability of 6-OHDA to block the behavioral effects of L-5-HTP in lesioned rats was also observed after Ro 4-4602. In rats given Ro 4-4602, the accumulation of 5-HT at 90 minutes after injection of L-5-HTP was significantly correlated (r = 0.98) with total monoamine content. Thus, 6-OHDA pretreatment significantly decreased the net accumulation of 5-HT from L-5-HTP in nonlesioned rats. These rats also demonstrated further decreases in norepinephrine and dopamine content after L-5-HTP. It was concluded that L-5-HTP can be decarboxylated to 5-HT in serotonergic and catecholaminergic neurons and that the behavioral effects of L-5-HTP in lesioned rats may be due to the formation of 5-HT in catecholaminergic neurons where it may act as a \"false-transmitter.\"", "contents": "Behavioral effects of L-5-hydroxytryptophan after destruction of ascending serotonergic pathways in the rat: the role of catecholaminergic neurons. Lesions in the medial forebrain bundle of the rat produced a 68 to 74% decrease in telencephalic serotonin (5-HT) and a 30 to 43% decrease in jump threshold. L-5-Hydroxytryptophan (L-5-HTP; 37.5 mg/kg) returned the 5-HT content and jump threshold of lesioned rats to normal levels. These effects of L-5-HTP were also observed after the inhibition of extracerebral decarboxylase activity with Ro 4-4602 (50 mg/kg). Pretreatment with 6-hydroxydopamine (6-OHDA), which selectively destroys catecholamine neurons, had no effect on the jump threshold of nonlesioned rats nor did it further change the 5-HT content or jump threshold of lesioned rats. Lesioned rats pretreated with 6-OHDA demonstrated an increase in 5-HT content after L-5-HTP; however, their jump threshold remained significantly lower than that of controls. This ability of 6-OHDA to block the behavioral effects of L-5-HTP in lesioned rats was also observed after Ro 4-4602. In rats given Ro 4-4602, the accumulation of 5-HT at 90 minutes after injection of L-5-HTP was significantly correlated (r = 0.98) with total monoamine content. Thus, 6-OHDA pretreatment significantly decreased the net accumulation of 5-HT from L-5-HTP in nonlesioned rats. These rats also demonstrated further decreases in norepinephrine and dopamine content after L-5-HTP. It was concluded that L-5-HTP can be decarboxylated to 5-HT in serotonergic and catecholaminergic neurons and that the behavioral effects of L-5-HTP in lesioned rats may be due to the formation of 5-HT in catecholaminergic neurons where it may act as a \"false-transmitter.\""} {"id": "PMID:1255479", "title": "Opiate receptor interactions of benzomorphans in rat brain homogenates.", "content": "Minor structural variations of benzomorphans opiates are associated with striking, unpredictable shifts in the relative extent of agonist or antagonist properties in vivo. The relative abilities of a number of benzomorphans in inhibit 3H-naloxone binding in the absence and presence of sodium in vitro show some correlations with their pharmacologic properties in vivo, although distinct exceptions exist. The ability of opiate agonists to inhibit 3H-naloxone binding is greatly reduced by sodium, while pure antagonists are affected very little, if at all, and mixed agonist-antagonist benzomorphans display an intermediate response.", "contents": "Opiate receptor interactions of benzomorphans in rat brain homogenates. Minor structural variations of benzomorphans opiates are associated with striking, unpredictable shifts in the relative extent of agonist or antagonist properties in vivo. The relative abilities of a number of benzomorphans in inhibit 3H-naloxone binding in the absence and presence of sodium in vitro show some correlations with their pharmacologic properties in vivo, although distinct exceptions exist. The ability of opiate agonists to inhibit 3H-naloxone binding is greatly reduced by sodium, while pure antagonists are affected very little, if at all, and mixed agonist-antagonist benzomorphans display an intermediate response."} {"id": "PMID:1255480", "title": "Reduction of tryptophan hydroxylase activity and 5-hydroxytryptamine concentration in certain rat brain nuclei after p-chloroamphetamine.", "content": "High-pressure liquid chromatography and mass fragmentography have been used to determine tryptophan hydroxylase activity and 5-hydroxytryptamine (5-HT) concentration, respectively, in certain rat brain nuclei. (+/-)-p-Chloroamphetamine (100 mumol/kg i.p.) decreased enzyme activity in 5-HT terminals of the caudate, hippocampus and septum to a minimum level within 3 days. In hippocampus, but not in septum, the enzyme activity and 5-HT content remained maximally depleted (about 80%) for as long as 2 months after the p-chloroamphetamine injection. Of the 5-HT cell body areas investigated, only in the B9 nucleus was the tryptophan hydroxylase activity and 5-HT content still significantly reduced (about 25-50%) at 21 and 60 days after the drug injection. The enzyme activity and 5-HT content of the B7 and B8 nuclei were not significantly different from control values at these times. These results suggest that the primary site of action of p-chloroamphetamine is on nerve terminals followed by secondary effects on serotonergic cell bodies.", "contents": "Reduction of tryptophan hydroxylase activity and 5-hydroxytryptamine concentration in certain rat brain nuclei after p-chloroamphetamine. High-pressure liquid chromatography and mass fragmentography have been used to determine tryptophan hydroxylase activity and 5-hydroxytryptamine (5-HT) concentration, respectively, in certain rat brain nuclei. (+/-)-p-Chloroamphetamine (100 mumol/kg i.p.) decreased enzyme activity in 5-HT terminals of the caudate, hippocampus and septum to a minimum level within 3 days. In hippocampus, but not in septum, the enzyme activity and 5-HT content remained maximally depleted (about 80%) for as long as 2 months after the p-chloroamphetamine injection. Of the 5-HT cell body areas investigated, only in the B9 nucleus was the tryptophan hydroxylase activity and 5-HT content still significantly reduced (about 25-50%) at 21 and 60 days after the drug injection. The enzyme activity and 5-HT content of the B7 and B8 nuclei were not significantly different from control values at these times. These results suggest that the primary site of action of p-chloroamphetamine is on nerve terminals followed by secondary effects on serotonergic cell bodies."} {"id": "PMID:1255481", "title": "Effect of tetrahydrocannabinols on 3H-acetylcholine biosynthesis in various rat brain slices.", "content": "The effects of delta8- and delta9-tetrahydrocannabinol on the biosynthesis of 3H-acetylcholine (ACh) from 3H-choline in cortical, hypothalamic and striatal rat brain slices were examined. The two cannabinols were found to inhibit the synthesis of 3H-ACh in the three brain regions. Treatment with cannabidiol did not alter ACh synthesis. Delta8-tetrahydrocannabinol was approximately twice as effective as the delta9-isomer. This effect was not associated with alterations in striatal and cortical choline acetyltransferase or with an impaired high-affinity uptake system for choline in the striatum. Treatment with delta8- and delta9-cannabinols, likewise, did not change striatal choline and ACh levels. Antagonism of the ACh biosynthesis inhibition occurred when slices from treated animals were incubated in depolarizing concentration of K+ ion. These results suggest that the inhibition of ACh synthesis observed in tetrahydrocannabinol-treated rats may be related to interference with the propagated action potential or with the depolarization process in cholinergic neurons.", "contents": "Effect of tetrahydrocannabinols on 3H-acetylcholine biosynthesis in various rat brain slices. The effects of delta8- and delta9-tetrahydrocannabinol on the biosynthesis of 3H-acetylcholine (ACh) from 3H-choline in cortical, hypothalamic and striatal rat brain slices were examined. The two cannabinols were found to inhibit the synthesis of 3H-ACh in the three brain regions. Treatment with cannabidiol did not alter ACh synthesis. Delta8-tetrahydrocannabinol was approximately twice as effective as the delta9-isomer. This effect was not associated with alterations in striatal and cortical choline acetyltransferase or with an impaired high-affinity uptake system for choline in the striatum. Treatment with delta8- and delta9-cannabinols, likewise, did not change striatal choline and ACh levels. Antagonism of the ACh biosynthesis inhibition occurred when slices from treated animals were incubated in depolarizing concentration of K+ ion. These results suggest that the inhibition of ACh synthesis observed in tetrahydrocannabinol-treated rats may be related to interference with the propagated action potential or with the depolarization process in cholinergic neurons."} {"id": "PMID:1255482", "title": "Distribution and properties of adrenergic storage vesicles in nerve terminals.", "content": "The subcellular distribution of adrenergic storage vesicles was determined in rat spleen, heart and superior cervical ganglion and in dog spleen using dopamine-beta-hydroxylase (DBH) as a marker for vesicle membranes and norepinephrine (NE) as a marker for the soluble contents of the storage vesicles. Density gradient centrifugation revealed populations of vesicles in the rat heart and spleen with equilibrium densities of 1.05 and 1.15 g/ml. There was a consistent shoulder on the low-density peak at a density of 1.08 g/ml. Several populations of NE-and DBH-containing vesicles were also found in homogenates of dog spleen. In homogenates of superior cervical ganglia, most of the NE was nonsedimentable while the DBH activity formed a broad poorly resolved band within the gradient. Although NE and DBH were present in each of several populations of vesicles in nerve terminals of rat and dog organs, the ratio of NE/DBH varied as a function of the species and organ examined. Mitochondrial contamination did not, as has been previously claimed, influence the distribution of DBH which was observed. Both light and heavy vesicles were able to take up and retain NE-[3H].", "contents": "Distribution and properties of adrenergic storage vesicles in nerve terminals. The subcellular distribution of adrenergic storage vesicles was determined in rat spleen, heart and superior cervical ganglion and in dog spleen using dopamine-beta-hydroxylase (DBH) as a marker for vesicle membranes and norepinephrine (NE) as a marker for the soluble contents of the storage vesicles. Density gradient centrifugation revealed populations of vesicles in the rat heart and spleen with equilibrium densities of 1.05 and 1.15 g/ml. There was a consistent shoulder on the low-density peak at a density of 1.08 g/ml. Several populations of NE-and DBH-containing vesicles were also found in homogenates of dog spleen. In homogenates of superior cervical ganglia, most of the NE was nonsedimentable while the DBH activity formed a broad poorly resolved band within the gradient. Although NE and DBH were present in each of several populations of vesicles in nerve terminals of rat and dog organs, the ratio of NE/DBH varied as a function of the species and organ examined. Mitochondrial contamination did not, as has been previously claimed, influence the distribution of DBH which was observed. Both light and heavy vesicles were able to take up and retain NE-[3H]."} {"id": "PMID:1255483", "title": "Centrally mediated increased reflex vagal bradycardia after L-dopa in monoamine oxidase-inhibited anesthetized dogs.", "content": "In monoamine oxidase-inhibited dogs whose peripheral dopa decarboxylase was inhibited with MK-486, L-dopa (K mg/kg i.v.) caused significant hypotension and bradycardia. In addition, reflex bradycardia but not pressor responses to norepinephrine were markedly enhanced by the drug. Similar results were obtained after intracerebroventricular administration of L-dopa (0.5 mg/kg) in monoamine oxidase-inhibited dogs not receiving MK-486. Proparnolol prevented the bradycardia caused by L-dopa but was without effect on the reflex facilitation. Both atropine and phentolamine had no effect on L-dopa bradycardia but prevented the facilitatory effect on reflexes. Inhibition of both peripheral and central dopa decarboxylase with Ro 4-4602 prevented all the effects of L-dopa. Infusions of dopamine which had obvious cardiovascular effects had no effect on reflex responses to norepinephrine. It is concluded that L-dopa, after decarboxylation, causes a centrally mediated enhancement of reflex vagal bradycardia. Pharmacological analysis of this enhancement suggests that this effect appears to be a result of central alpha receptor stimulation.", "contents": "Centrally mediated increased reflex vagal bradycardia after L-dopa in monoamine oxidase-inhibited anesthetized dogs. In monoamine oxidase-inhibited dogs whose peripheral dopa decarboxylase was inhibited with MK-486, L-dopa (K mg/kg i.v.) caused significant hypotension and bradycardia. In addition, reflex bradycardia but not pressor responses to norepinephrine were markedly enhanced by the drug. Similar results were obtained after intracerebroventricular administration of L-dopa (0.5 mg/kg) in monoamine oxidase-inhibited dogs not receiving MK-486. Proparnolol prevented the bradycardia caused by L-dopa but was without effect on the reflex facilitation. Both atropine and phentolamine had no effect on L-dopa bradycardia but prevented the facilitatory effect on reflexes. Inhibition of both peripheral and central dopa decarboxylase with Ro 4-4602 prevented all the effects of L-dopa. Infusions of dopamine which had obvious cardiovascular effects had no effect on reflex responses to norepinephrine. It is concluded that L-dopa, after decarboxylation, causes a centrally mediated enhancement of reflex vagal bradycardia. Pharmacological analysis of this enhancement suggests that this effect appears to be a result of central alpha receptor stimulation."} {"id": "PMID:1255484", "title": "Central effect of beta adrenergic blocking agents on arterial blood pressure.", "content": "dl-Sotalol, dl-pindolol, d-propranolol and dl-propranolol were evaluated for central hypotensive activity in chloralose-anesthetized vagotomized cats. Blood pressure and average evoked potentials recorded from one postganglionic renal nerve were measured during intraventricular (lateral ventricle) or intravenous (radial vein) infusion of each agent. Potentials were evoked in the sympathetic nerve by single shocks to the sciatic nerve. Three concentrations (1, 3, 5 mM) of each compound were infused consecutively for 20 minutes per concentration. The decrease in blood pressure after intraventricular infusion of 1 mM pindolol, 5 mM d-propranolol and 3 mM dl-propranolol was significantly greater than the decrease after intravenous infusion of the same concentrations of each agent. The decrease in the average evoked potential after intraventricular infusion of the 5 mM concentration was greater than the response after intravenous infusion. Consecutive (1, 3, 5 mM) intraventricular or intravenous infusions of sotalol did not significantly change either parameter. During intraventricular infusion of 3 mM dl-propranolol blood pressures was markedly decreased at a time when the average evoked potential was unchanged; however, parallel changes were observed during infusion of the drug in vagotomized cats in which the carotid sinus baroreceptors were also denervated. The results indicate a) that intraventricular administration of d-propranolol, dl-propranolol and dl-pindolol, but not of dl-sotalol, decreased blood pressure and discharge evoked in the postganglionic renal nerve by an action on central sympathetic structures, and b) that baroreceptor activity during hypotension can overcome the depressant effect of dl-propranolol on potentials evoked reflexly in the renal nerve.", "contents": "Central effect of beta adrenergic blocking agents on arterial blood pressure. dl-Sotalol, dl-pindolol, d-propranolol and dl-propranolol were evaluated for central hypotensive activity in chloralose-anesthetized vagotomized cats. Blood pressure and average evoked potentials recorded from one postganglionic renal nerve were measured during intraventricular (lateral ventricle) or intravenous (radial vein) infusion of each agent. Potentials were evoked in the sympathetic nerve by single shocks to the sciatic nerve. Three concentrations (1, 3, 5 mM) of each compound were infused consecutively for 20 minutes per concentration. The decrease in blood pressure after intraventricular infusion of 1 mM pindolol, 5 mM d-propranolol and 3 mM dl-propranolol was significantly greater than the decrease after intravenous infusion of the same concentrations of each agent. The decrease in the average evoked potential after intraventricular infusion of the 5 mM concentration was greater than the response after intravenous infusion. Consecutive (1, 3, 5 mM) intraventricular or intravenous infusions of sotalol did not significantly change either parameter. During intraventricular infusion of 3 mM dl-propranolol blood pressures was markedly decreased at a time when the average evoked potential was unchanged; however, parallel changes were observed during infusion of the drug in vagotomized cats in which the carotid sinus baroreceptors were also denervated. The results indicate a) that intraventricular administration of d-propranolol, dl-propranolol and dl-pindolol, but not of dl-sotalol, decreased blood pressure and discharge evoked in the postganglionic renal nerve by an action on central sympathetic structures, and b) that baroreceptor activity during hypotension can overcome the depressant effect of dl-propranolol on potentials evoked reflexly in the renal nerve."} {"id": "PMID:1255485", "title": "The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig.", "content": "The effects of 2 to 10 muM verapamil (1-5 mg/l) and 3.8 to 7.6 muM quinidine (2-4 mg/l) on automaticity in ventricular myocardial fibers were examined. Papillary muscles from guinea pigs were mounted in a sucrose gap chamber and transmembrane potential was recorded by standard microelectrode techniques. Automaticity was induced with depolarizing currents of various strengths. Verapamil reduced phase 4 slope at all maximum diastolic membrane potentials. It also caused a selective reduction of the overshoot of action potentials arising from less negative maximum diastolic potentials. During exposure to verapamil, increased [Ca]0 partially restored action potential overshoot, but phase 4 slope was further reduced. Epinephrine caused a partial or complete reversal of verapamil-induced phase 4 slope depression but usually did not restore action potential overshoot. Quinidine reduced phase 4 slope at all maximum diastolic potentials. There was less marked reduction of action potential overshoot than in the case of verapamil. Epinephrine caused a partial reversal of the reduction of phase 4 slope produced by quinidine. It is concluded that although both verapamil and quinidine reduce automaticity in ventricular fibers, verapamil may be more effective in reducing the amplitude and occurrence of action potentials arising from low maximum diastolic potentials.", "contents": "The effects of quinidine and verapamil on electrically induced automaticity in the ventricular myocardium of guinea pig. The effects of 2 to 10 muM verapamil (1-5 mg/l) and 3.8 to 7.6 muM quinidine (2-4 mg/l) on automaticity in ventricular myocardial fibers were examined. Papillary muscles from guinea pigs were mounted in a sucrose gap chamber and transmembrane potential was recorded by standard microelectrode techniques. Automaticity was induced with depolarizing currents of various strengths. Verapamil reduced phase 4 slope at all maximum diastolic membrane potentials. It also caused a selective reduction of the overshoot of action potentials arising from less negative maximum diastolic potentials. During exposure to verapamil, increased [Ca]0 partially restored action potential overshoot, but phase 4 slope was further reduced. Epinephrine caused a partial or complete reversal of verapamil-induced phase 4 slope depression but usually did not restore action potential overshoot. Quinidine reduced phase 4 slope at all maximum diastolic potentials. There was less marked reduction of action potential overshoot than in the case of verapamil. Epinephrine caused a partial reversal of the reduction of phase 4 slope produced by quinidine. It is concluded that although both verapamil and quinidine reduce automaticity in ventricular fibers, verapamil may be more effective in reducing the amplitude and occurrence of action potentials arising from low maximum diastolic potentials."} {"id": "PMID:1255486", "title": "The effects of batrachotoxin on cat papillary muscle.", "content": "The effects of batrachotoxin (BTX) upon the contraction and transmembrane potential of cat right ventricular papillary muscles were studied in vitro at 37 degrees C. BTX (2.0 x 10(-9) M) increased isometric contractile force by about 50% from control force, decreased the potential difference across the cell membrane to approximate -50 mV and produced spontaneous contractions of the papillary muscles. Each BTX-induced spontaneous contraction was accompanied by a spontaneous action potential which was generated when an oscillation in membrane potential reached threshold level. Spontaneous activity ovvurred only in muscles which were previously stimulated electrically. The positive inotropic effect of BTX was accompanied by an increase in the rate of force development. Papillary muscles from cats pretreated with reserpine did not differ from normal muscles in their responses to BTX treatment. Tetrodotoxin (2.0 x 10(-7) M) antagonized the effects of BTX, a finding which suggests that the actions of BTX are mediated by a selective increase in membrane permeability to sodium ions. The resultant BTX-elicited increase in the intracellular sodium ion concentration may increase the force of contraction through an augmentation of calcium influx via the sodium-calcium exchange system.", "contents": "The effects of batrachotoxin on cat papillary muscle. The effects of batrachotoxin (BTX) upon the contraction and transmembrane potential of cat right ventricular papillary muscles were studied in vitro at 37 degrees C. BTX (2.0 x 10(-9) M) increased isometric contractile force by about 50% from control force, decreased the potential difference across the cell membrane to approximate -50 mV and produced spontaneous contractions of the papillary muscles. Each BTX-induced spontaneous contraction was accompanied by a spontaneous action potential which was generated when an oscillation in membrane potential reached threshold level. Spontaneous activity ovvurred only in muscles which were previously stimulated electrically. The positive inotropic effect of BTX was accompanied by an increase in the rate of force development. Papillary muscles from cats pretreated with reserpine did not differ from normal muscles in their responses to BTX treatment. Tetrodotoxin (2.0 x 10(-7) M) antagonized the effects of BTX, a finding which suggests that the actions of BTX are mediated by a selective increase in membrane permeability to sodium ions. The resultant BTX-elicited increase in the intracellular sodium ion concentration may increase the force of contraction through an augmentation of calcium influx via the sodium-calcium exchange system."} {"id": "PMID:1255487", "title": "Effect of adenosine on myocardial oxygen balance.", "content": "The present study was designed to determine the effect of adenosine on oxyhemoglobin equilibrium (P-50) and myocardial oxygen consumption (MVO2) in the isolated supported dog heart preparation perfused at a constant coronary blood flow. Heart rate was controlled at 150 beats/min. A-3-minute intracoronary infusion of adenosine (10, 50 and 100 mug/min) produced significant decreases in MVO2, whereas coronary venous P-50 did not change. Adenosine-5'-monophosphate (5'-AMP) infusion (70 and 140 mug/min) did not produce a significant change in MVO2. Both adenosine and 5'-AMP caused equivalent decreases in coronary artery perfusion pressure and peak left ventricular systolic pressure. Furthermore, adenosine (50 and 100 mug/min) produced a significant decrease in MVO2 of the isolated supported fibrillating heart. These results suggest that the reduction in MVO2 observed with adenosine is not related to coronary vasodilation or to a negative inotropic or chronotropic action. Theophylline (2.5 mg/kg) partially blocked the hemodynamic effects of adenosine while completely abolishing the decrease in MVO2. Neither inosine nor hypoxanthine (50 and 100 mug/min) changed MVO2, P-50 or myocardial hemodynamics. Thus, in addition to its proposed role in coronary blood flow regulation, adenosine appears to exert important effects on myocardial metabolism.", "contents": "Effect of adenosine on myocardial oxygen balance. The present study was designed to determine the effect of adenosine on oxyhemoglobin equilibrium (P-50) and myocardial oxygen consumption (MVO2) in the isolated supported dog heart preparation perfused at a constant coronary blood flow. Heart rate was controlled at 150 beats/min. A-3-minute intracoronary infusion of adenosine (10, 50 and 100 mug/min) produced significant decreases in MVO2, whereas coronary venous P-50 did not change. Adenosine-5'-monophosphate (5'-AMP) infusion (70 and 140 mug/min) did not produce a significant change in MVO2. Both adenosine and 5'-AMP caused equivalent decreases in coronary artery perfusion pressure and peak left ventricular systolic pressure. Furthermore, adenosine (50 and 100 mug/min) produced a significant decrease in MVO2 of the isolated supported fibrillating heart. These results suggest that the reduction in MVO2 observed with adenosine is not related to coronary vasodilation or to a negative inotropic or chronotropic action. Theophylline (2.5 mg/kg) partially blocked the hemodynamic effects of adenosine while completely abolishing the decrease in MVO2. Neither inosine nor hypoxanthine (50 and 100 mug/min) changed MVO2, P-50 or myocardial hemodynamics. Thus, in addition to its proposed role in coronary blood flow regulation, adenosine appears to exert important effects on myocardial metabolism."} {"id": "PMID:1255488", "title": "Active transport of phenol red by rat lung slices.", "content": "32S-phenol red was taken up by rat lung slices incubated in oxygenated Krebs-Ringer phosphate-glucose solution (pH 7.4) at 37 degrees C by a process showing the characteristics of active transport. Uptake against a concentration gradient occurred by a saturable process that was inhibited by low temperature, anaerobic conditions and certain metabolic inhibitors. Phenol red uptake was depressed in the presence of certain anionic dyes, such as chlorphenol red, bromphenol blue, bromthymol blue and bromcresol green, and by various other organic acids, including disodium cromoglycate, probenecid, cephalothin and benzylpenicillin. In contrast, isoniazid and p-aminohippuric acid had no effect on phenol red uptake, suggesting that a specificity exists in the rat lung for transport of anionic compounds. Interestingly, in the presence of paraquat, an organic cation,phenol red uptake was increased. The extent of uptake of phenol red by lung slices was dependent on levels of Na, K and Ca ion in the incubation medium as well as on the thickness of the tissue slice. Phenol red was bound to lung homogenates; however, the characteristics of the binding were such that binding alone could not account for accumulation by lung slices.", "contents": "Active transport of phenol red by rat lung slices. 32S-phenol red was taken up by rat lung slices incubated in oxygenated Krebs-Ringer phosphate-glucose solution (pH 7.4) at 37 degrees C by a process showing the characteristics of active transport. Uptake against a concentration gradient occurred by a saturable process that was inhibited by low temperature, anaerobic conditions and certain metabolic inhibitors. Phenol red uptake was depressed in the presence of certain anionic dyes, such as chlorphenol red, bromphenol blue, bromthymol blue and bromcresol green, and by various other organic acids, including disodium cromoglycate, probenecid, cephalothin and benzylpenicillin. In contrast, isoniazid and p-aminohippuric acid had no effect on phenol red uptake, suggesting that a specificity exists in the rat lung for transport of anionic compounds. Interestingly, in the presence of paraquat, an organic cation,phenol red uptake was increased. The extent of uptake of phenol red by lung slices was dependent on levels of Na, K and Ca ion in the incubation medium as well as on the thickness of the tissue slice. Phenol red was bound to lung homogenates; however, the characteristics of the binding were such that binding alone could not account for accumulation by lung slices."} {"id": "PMID:1255489", "title": "Effect of prolonged lithium ingestion on the response to mineralocorticoids in rats.", "content": "The effect of long-term lithium administration on the response to mineralocorticoids was studied in rats which were adrenalectomized in order to avoid the effects of endogenous hormone. The hormone response was estimated from the changes in urinary excretion of sodium and potassium in rats on low and high sodium intake and from the consumption of a hypertonic NaCl solution by rats given a free choice between this and demineralized water. Lithium was found to lower the response to aldosterone and deoxycorticosterone acetate both in acute and chronic experiments. It was further found that in adrenalectomized rats given no hormone, those given lithium consumed significantly more NaCl solution than those given no lithium. The experiments therefore provide evidence that lithium induces a sodium requirement beyond that induced by the inhibition of the response to mineralocorticoids.", "contents": "Effect of prolonged lithium ingestion on the response to mineralocorticoids in rats. The effect of long-term lithium administration on the response to mineralocorticoids was studied in rats which were adrenalectomized in order to avoid the effects of endogenous hormone. The hormone response was estimated from the changes in urinary excretion of sodium and potassium in rats on low and high sodium intake and from the consumption of a hypertonic NaCl solution by rats given a free choice between this and demineralized water. Lithium was found to lower the response to aldosterone and deoxycorticosterone acetate both in acute and chronic experiments. It was further found that in adrenalectomized rats given no hormone, those given lithium consumed significantly more NaCl solution than those given no lithium. The experiments therefore provide evidence that lithium induces a sodium requirement beyond that induced by the inhibition of the response to mineralocorticoids."} {"id": "PMID:1255490", "title": "Studies on the binding of 5,5-diphenyl-hydantoin to nucleic acids in vitro and to rat brain subcellular fractions in vitro and in vivo.", "content": "The binding of 5,5-diphenylhydantoin (DPH) to nucleic acids (bovine brain RNA, rat liver ribosomal and tRNA, Torula utilis RNA, and calf thymus and Escherichia coli DNA was studied using ultraviolet spectroscopy, gel chromatography and thermal transition profiles. Within the sensitivity of these methods, it was found that there is essentially little or no interaction between DPH and nucleic acids in vitro as has been reported previously. Little, if any evidence of DPH intercalation with DNA was noted during thermal transition studies. DPH does not interfere with DNA reassociation. Further studies into the nature of the in vivo subcellular distribution of 14C-DPH in rat brain revealed accumulation of the radioactivity primarily in the soluble fractions. The nuclear fraction and the microsomes, containing high DNA and RNA tissue ratios, demonstrated the greatest particulate association with radioactivity at 2 and 12 hours, respectively. This association with particulate fractions was not demonstrated after gel chromatography. These data do not support a hypothesis relating DPH binding to nucleic acids in vitro or in vivo to a possible mechanism of action of the drug.", "contents": "Studies on the binding of 5,5-diphenyl-hydantoin to nucleic acids in vitro and to rat brain subcellular fractions in vitro and in vivo. The binding of 5,5-diphenylhydantoin (DPH) to nucleic acids (bovine brain RNA, rat liver ribosomal and tRNA, Torula utilis RNA, and calf thymus and Escherichia coli DNA was studied using ultraviolet spectroscopy, gel chromatography and thermal transition profiles. Within the sensitivity of these methods, it was found that there is essentially little or no interaction between DPH and nucleic acids in vitro as has been reported previously. Little, if any evidence of DPH intercalation with DNA was noted during thermal transition studies. DPH does not interfere with DNA reassociation. Further studies into the nature of the in vivo subcellular distribution of 14C-DPH in rat brain revealed accumulation of the radioactivity primarily in the soluble fractions. The nuclear fraction and the microsomes, containing high DNA and RNA tissue ratios, demonstrated the greatest particulate association with radioactivity at 2 and 12 hours, respectively. This association with particulate fractions was not demonstrated after gel chromatography. These data do not support a hypothesis relating DPH binding to nucleic acids in vitro or in vivo to a possible mechanism of action of the drug."} {"id": "PMID:1255491", "title": "The development of new iron-chelating drugs.", "content": "2,3-Dihydroxybenzoic acid has been identified as a potentially useful iron-chelating drug. Accordingly, we have evaluated a series of derivatives of hydroxylated benzoic acids for their ability to induce iron excretion in the iron-overloaded rat. In addition, we have examined a number of hydroxamic acids and some other naturally occurring iron-chelating agents. Of the 26 benzoic acid derivatives studied, none appeared to be more effective than 2,3-dihydroxybenzoic acid, for reasons which are discussed. Rhodotorulic acid, a hydroxamic acid produced by and isolated from cultures of Rhodotorula pilimanae, was the most effective of all the compounds studied in inducing iron excretion. When administered parenterally, rholotorulic acid induced iron excretion via both the urinary and the fecal routes and was more than twice as potent (on a weight basis) as desferrioxamine. Two ferrous chelators, alpha, alpha-dipyridyl ad 1,10-phenanthroline, induced a moderate amount of iron excretion, suggesting that a pool of ferrous iron may be available for chelation.", "contents": "The development of new iron-chelating drugs. 2,3-Dihydroxybenzoic acid has been identified as a potentially useful iron-chelating drug. Accordingly, we have evaluated a series of derivatives of hydroxylated benzoic acids for their ability to induce iron excretion in the iron-overloaded rat. In addition, we have examined a number of hydroxamic acids and some other naturally occurring iron-chelating agents. Of the 26 benzoic acid derivatives studied, none appeared to be more effective than 2,3-dihydroxybenzoic acid, for reasons which are discussed. Rhodotorulic acid, a hydroxamic acid produced by and isolated from cultures of Rhodotorula pilimanae, was the most effective of all the compounds studied in inducing iron excretion. When administered parenterally, rholotorulic acid induced iron excretion via both the urinary and the fecal routes and was more than twice as potent (on a weight basis) as desferrioxamine. Two ferrous chelators, alpha, alpha-dipyridyl ad 1,10-phenanthroline, induced a moderate amount of iron excretion, suggesting that a pool of ferrous iron may be available for chelation."} {"id": "PMID:1255492", "title": "Biliary excretion of 3,4-benzpyrene in nafenopin-treated rats.", "content": "When rats treated for 2 days with nafenopin are injected i.v. with 3H-3,4-benzpyrene (BP), blood disappearance rates and liver levels of the carcinogen and the rate of biliary excretion of its metabolites are, in the main, similar to those of nontreated rats. This is in accord with the observation that nafenopin does not inhibit the metabolism of BP, which is the rate-limiting step in its biliary excretion. On the other hand, when 3H-BP metabolites are injected, nafenopin pretreatment slightly retards their rate of plasma disappearance and markedly inhibits their biliary excretion, as it does other organic anions. When rats are pretreated with 3-methylcholanthrene, the rate of metabolism of 3H-BP and consequently the biliary excretion of its metabolites is greatly stimulated. In this instance, metabolism may no longer be rate-limiting in the overall biliary excretion process and inhibition by nafenopin of liver-to-bile transport of metabolites can be observed. Since nafenopin pretreatment stimulates the synthesis of new liver tissue, it is presently a matter of conjecture as to whether or not the newly formed hepatocytes have the capacity to take up and excrete BP and its metabolites or whether nafenopin inhibits transport in all liver tissue.", "contents": "Biliary excretion of 3,4-benzpyrene in nafenopin-treated rats. When rats treated for 2 days with nafenopin are injected i.v. with 3H-3,4-benzpyrene (BP), blood disappearance rates and liver levels of the carcinogen and the rate of biliary excretion of its metabolites are, in the main, similar to those of nontreated rats. This is in accord with the observation that nafenopin does not inhibit the metabolism of BP, which is the rate-limiting step in its biliary excretion. On the other hand, when 3H-BP metabolites are injected, nafenopin pretreatment slightly retards their rate of plasma disappearance and markedly inhibits their biliary excretion, as it does other organic anions. When rats are pretreated with 3-methylcholanthrene, the rate of metabolism of 3H-BP and consequently the biliary excretion of its metabolites is greatly stimulated. In this instance, metabolism may no longer be rate-limiting in the overall biliary excretion process and inhibition by nafenopin of liver-to-bile transport of metabolites can be observed. Since nafenopin pretreatment stimulates the synthesis of new liver tissue, it is presently a matter of conjecture as to whether or not the newly formed hepatocytes have the capacity to take up and excrete BP and its metabolites or whether nafenopin inhibits transport in all liver tissue."} {"id": "PMID:1255493", "title": "The participation of 2-butanone in 2-butanol-induced potentiation of carbon tetrachloride hepatotoxicity.", "content": "The role of alcohol metabolism in 2-butanol-induced potentiation of carbon tetrachloride (CCl4) hepatotoxicity was studied in rats. Animals were sacrificed at various times after the administration of 2-butanol (2.2 ml/kg p.o.) for the determination of blood 2-butanol and 2-butanone concentrations by gas chromatographic analysis. 2-butanol exhibited an apparent elimination half-life of 2.5 hours. With the decline of 2-butanol concentrations, there was a rise in 2-butanone blood concentrations with 43 mg/100 ml detected at 1 hour and a maximum of 105 mg/100 ml detected 4 hours after the administration of the alcohol. A 16-hour pretreatment with either 2-butanol (2.2 ml/kg p.o.) or 2-butanone (1.87 ml/kg p.o.) markedly enhanced the hepatotoxic response of CCl4 (0.1 ml/kg i.p.) as measured by serum glutamic pyruvic transaminase activity, hepatic glucose-6-phosphatase activity and triglyceride content. The enhanced hepatotoxicity produced by 2-butanol was not significantly different from that produced by 2-butanone. The potentiation of CCl4 hepatotoxicity by both agents was substantiated morphologically. The results indicate that 2-butanone production via the oxidation of 2-butanol appears to contribute to the marked response of 2-butanol.", "contents": "The participation of 2-butanone in 2-butanol-induced potentiation of carbon tetrachloride hepatotoxicity. The role of alcohol metabolism in 2-butanol-induced potentiation of carbon tetrachloride (CCl4) hepatotoxicity was studied in rats. Animals were sacrificed at various times after the administration of 2-butanol (2.2 ml/kg p.o.) for the determination of blood 2-butanol and 2-butanone concentrations by gas chromatographic analysis. 2-butanol exhibited an apparent elimination half-life of 2.5 hours. With the decline of 2-butanol concentrations, there was a rise in 2-butanone blood concentrations with 43 mg/100 ml detected at 1 hour and a maximum of 105 mg/100 ml detected 4 hours after the administration of the alcohol. A 16-hour pretreatment with either 2-butanol (2.2 ml/kg p.o.) or 2-butanone (1.87 ml/kg p.o.) markedly enhanced the hepatotoxic response of CCl4 (0.1 ml/kg i.p.) as measured by serum glutamic pyruvic transaminase activity, hepatic glucose-6-phosphatase activity and triglyceride content. The enhanced hepatotoxicity produced by 2-butanol was not significantly different from that produced by 2-butanone. The potentiation of CCl4 hepatotoxicity by both agents was substantiated morphologically. The results indicate that 2-butanone production via the oxidation of 2-butanol appears to contribute to the marked response of 2-butanol."} {"id": "PMID:1255494", "title": "Expiratory measurement of maximal amino-pyrine demethylation in vivo: effect of phenobarbital, partial hepatectomy, protacaval shunt and bile duct ligation in the rat.", "content": "Current in vivo methods do not give information about the drug-metabolizing capacity (Vmax) and the affinity of the microsomal enzyme system for the drug i.e., the dose yielding Vmax/2 (Kd). To explore the possibility of estimating these variables from demethylation rates measured by 14CO2 exhalation, various doses of 14C-aminopyrine were injected i.v. to unanesthetized rats. Drug clearances based on 14CO2 exhalation agreed well with those derived from plasma disappearance rates. Evaluation of dose-response curves revealed saturation phenomena. In the normal rat, a Vmax of 173 nmol/min/100 g and Kd of 26 mumol/100 g could be calculated. Enzyme induction with phenobarbital increased Vmax to 745 nmol/min/100 g, whereas in the rat with portacaval shunt, it was reduced to 45 nmol/min/100 g. After 48-hour bile duct ligation, Vmax was not significantly different from the controls, but Kd increased to 36 mumol/100 g compatible with a competitive type of inhibition of aminopyrine demethylation. Two-thirds hepatectomy reduced Vmax by only 50% suggesting that a substantial portion of demethylation occurs extrahepatically. The approach presented appears to be a valid alternative to conventional plasma clearance methods allowing interpretation of some mechanisms affecting in vivo drug metabolism under various conditions.", "contents": "Expiratory measurement of maximal amino-pyrine demethylation in vivo: effect of phenobarbital, partial hepatectomy, protacaval shunt and bile duct ligation in the rat. Current in vivo methods do not give information about the drug-metabolizing capacity (Vmax) and the affinity of the microsomal enzyme system for the drug i.e., the dose yielding Vmax/2 (Kd). To explore the possibility of estimating these variables from demethylation rates measured by 14CO2 exhalation, various doses of 14C-aminopyrine were injected i.v. to unanesthetized rats. Drug clearances based on 14CO2 exhalation agreed well with those derived from plasma disappearance rates. Evaluation of dose-response curves revealed saturation phenomena. In the normal rat, a Vmax of 173 nmol/min/100 g and Kd of 26 mumol/100 g could be calculated. Enzyme induction with phenobarbital increased Vmax to 745 nmol/min/100 g, whereas in the rat with portacaval shunt, it was reduced to 45 nmol/min/100 g. After 48-hour bile duct ligation, Vmax was not significantly different from the controls, but Kd increased to 36 mumol/100 g compatible with a competitive type of inhibition of aminopyrine demethylation. Two-thirds hepatectomy reduced Vmax by only 50% suggesting that a substantial portion of demethylation occurs extrahepatically. The approach presented appears to be a valid alternative to conventional plasma clearance methods allowing interpretation of some mechanisms affecting in vivo drug metabolism under various conditions."} {"id": "PMID:1255495", "title": "The effect of acetazolamide on the movements of anions into the posterior chamber of the dog eye.", "content": "The rate of entry of bicarbonate and chloride ions the posterior chamber of the dog, a species that has both HCO3- and Cl- concentrations in excess of plasma in this chamber, was measured in order to clarify the mechanisms involved in the produciton of aqueous humor. Four animals were given H14CO3- and 36Cl- intravenously first in a control series and then after pretreatment with acetazolamide, (50 mg/kg), a carbonci anhydrase inhibitor. Samples were taken from arterial blood and the posterior chamber. Acetazolamide did not affect chloride entry into the posterior chamber but bicarbonate entry was decreased about 50%. It is concluded that in this species, bicarbonate is the key anion for the decrease of aqueous humor production caused by the administration of acetazolamide.", "contents": "The effect of acetazolamide on the movements of anions into the posterior chamber of the dog eye. The rate of entry of bicarbonate and chloride ions the posterior chamber of the dog, a species that has both HCO3- and Cl- concentrations in excess of plasma in this chamber, was measured in order to clarify the mechanisms involved in the produciton of aqueous humor. Four animals were given H14CO3- and 36Cl- intravenously first in a control series and then after pretreatment with acetazolamide, (50 mg/kg), a carbonci anhydrase inhibitor. Samples were taken from arterial blood and the posterior chamber. Acetazolamide did not affect chloride entry into the posterior chamber but bicarbonate entry was decreased about 50%. It is concluded that in this species, bicarbonate is the key anion for the decrease of aqueous humor production caused by the administration of acetazolamide."} {"id": "PMID:1255496", "title": "Stereospecific radioimmunoassay for propranolol isomers.", "content": "Antisera against propranolol were produced in rabbits immunized with propranolol conjugated to bovine serum albumin. The antiserum against dl-propranolol recognized both d- and l-propranolol to the same degree. However, antiserum against l-propranolol was able to discriminate the l-propranolol selectively. The antisera were used to develop radioimmunoassays for dl-propranolol and l-propranolol. The assay can detect as little as 10 pg of propranolol. Metabolites of propranolol do not interfere with the assay unless concentrations are very high. Serum and heart levels of l-propranolol and the d-isomer were determined in the rat after i.v. injection (1 mg/kg) of dl-propranolol. l-Propranolol declines rapidly in the blood after the injection. Concomitantly, there is a rapid accumulation of l-propranolol by the heart. The d-form of propranolol remains in the blood and is metabolized rapidly as reflected by a shorter half-life (23.8 minutes) than the one found for l-propranolol (5.20 minutes).", "contents": "Stereospecific radioimmunoassay for propranolol isomers. Antisera against propranolol were produced in rabbits immunized with propranolol conjugated to bovine serum albumin. The antiserum against dl-propranolol recognized both d- and l-propranolol to the same degree. However, antiserum against l-propranolol was able to discriminate the l-propranolol selectively. The antisera were used to develop radioimmunoassays for dl-propranolol and l-propranolol. The assay can detect as little as 10 pg of propranolol. Metabolites of propranolol do not interfere with the assay unless concentrations are very high. Serum and heart levels of l-propranolol and the d-isomer were determined in the rat after i.v. injection (1 mg/kg) of dl-propranolol. l-Propranolol declines rapidly in the blood after the injection. Concomitantly, there is a rapid accumulation of l-propranolol by the heart. The d-form of propranolol remains in the blood and is metabolized rapidly as reflected by a shorter half-life (23.8 minutes) than the one found for l-propranolol (5.20 minutes)."} {"id": "PMID:1255500", "title": "The effects of lithium and sodium on the potassium conductance of snail neurones.", "content": "1. The iontophoretic injection of lithium into snail neurones reversibly increased the resting relative potassium permeability (PK). 2. Long exposures to snail Ringer containing 25 mM-Li and correspondingly reduced Na also caused an increase in PK. This did not occur with Ringer in which the same reduction of Na was made by replacing it with Tris. 3. Replacement of part of the Ringer Na by either Li or Tris led to proportional decreases in internal Na. 4. Injecting large quantities of Na into ouabain-treated cells caused effects similar to those of Li injection. Without ouabain, Na injection stimulated the electrogenic Na pump. 5. A number of tests failed to produce any clear evidence that intracellular Ca was involved in the response to Li.", "contents": "The effects of lithium and sodium on the potassium conductance of snail neurones. 1. The iontophoretic injection of lithium into snail neurones reversibly increased the resting relative potassium permeability (PK). 2. Long exposures to snail Ringer containing 25 mM-Li and correspondingly reduced Na also caused an increase in PK. This did not occur with Ringer in which the same reduction of Na was made by replacing it with Tris. 3. Replacement of part of the Ringer Na by either Li or Tris led to proportional decreases in internal Na. 4. Injecting large quantities of Na into ouabain-treated cells caused effects similar to those of Li injection. Without ouabain, Na injection stimulated the electrogenic Na pump. 5. A number of tests failed to produce any clear evidence that intracellular Ca was involved in the response to Li."} {"id": "PMID:1255501", "title": "The contractile state of rabbit papillary muscle in relation to stimulation frequency.", "content": "1. The relationship between active force and stimulation frequency (0-25-5/sec) was studied at 36-37 degrees C in isolated papillary muscles of the rabbit. 2. The muscle's force producing capability at a given frequency was determined as the isometric twitch response to a test stimulus that was applied at various times after a priming period. The optimum contractile response was obtained at an interval of 0-8 sec between the test pulse and the last stimulus of the priming period. 3. The optimum contractile response exceeded the steady-state twitch amplitude at all stimulation frequencies higher than 1/sec. While the steady-state twitch resonse declined at frequencies higher than 4/sec, the optimum contractile response was steadily increased as the stimulation frequency was raised. 4. The optimum contractile response was also determined after priming the muscle with a sinusoidal a.c. pulse (field strength, 10 V (r.m.s.)/cm; frequency, 20 c/s; duration, 2-5 sec). The optimum contractile response obtained after a.c. stimulation was 2-2 times greater than the maximal steady-state response. Its absolute value was 67-3+/-6-1 mN/mm2 (mean +/-S.E. of mean, n = 6). 5. The twitch potentiation produced by priming the muscle at a given frequency decayed exponentially in two phases after optimum contractile response had been attained. The time constants of the two phases, determined after a.c. stimulation, were 2-6+/-0-8 (n = 4) and 92-0+/-13-3 sec (n = 7), respectively. 6. The optimum contractile response determined at various stimulation frequencies was linearly related to the fraction of time during which the cell membrane was depolarized (beyond -40 mV) by the action potentials. 7. The results are interpreted in terms of a two-component model of the metabolism of activator calcium in the excitation-contraction coupling.", "contents": "The contractile state of rabbit papillary muscle in relation to stimulation frequency. 1. The relationship between active force and stimulation frequency (0-25-5/sec) was studied at 36-37 degrees C in isolated papillary muscles of the rabbit. 2. The muscle's force producing capability at a given frequency was determined as the isometric twitch response to a test stimulus that was applied at various times after a priming period. The optimum contractile response was obtained at an interval of 0-8 sec between the test pulse and the last stimulus of the priming period. 3. The optimum contractile response exceeded the steady-state twitch amplitude at all stimulation frequencies higher than 1/sec. While the steady-state twitch resonse declined at frequencies higher than 4/sec, the optimum contractile response was steadily increased as the stimulation frequency was raised. 4. The optimum contractile response was also determined after priming the muscle with a sinusoidal a.c. pulse (field strength, 10 V (r.m.s.)/cm; frequency, 20 c/s; duration, 2-5 sec). The optimum contractile response obtained after a.c. stimulation was 2-2 times greater than the maximal steady-state response. Its absolute value was 67-3+/-6-1 mN/mm2 (mean +/-S.E. of mean, n = 6). 5. The twitch potentiation produced by priming the muscle at a given frequency decayed exponentially in two phases after optimum contractile response had been attained. The time constants of the two phases, determined after a.c. stimulation, were 2-6+/-0-8 (n = 4) and 92-0+/-13-3 sec (n = 7), respectively. 6. The optimum contractile response determined at various stimulation frequencies was linearly related to the fraction of time during which the cell membrane was depolarized (beyond -40 mV) by the action potentials. 7. The results are interpreted in terms of a two-component model of the metabolism of activator calcium in the excitation-contraction coupling."} {"id": "PMID:1255502", "title": "Developmental aspects of potassium flux and permeability of the embryonic chick heart.", "content": "1. The rate coefficient of 42K efflux, the transmembrane potential, the intracellular concentrations of Na and K and the volume/surface area have been measured in embryonic chick hearts of different ages. 2. With respect to age, the rate coefficient for 42K efflux was minimal for preparations from 6-8 day old embryos, and distinctly higher values were obtained for the hearts of 3-5 and 18-20 days. With respect to the effect of external K concentration (Ko), all age groups showed a five- to sevenfold increase in rate coefficient between 2-5 and 140 mM-Ko. The effect of Ko was found to be indepedent of extracellular Na, except in the 18-20 day hearts bathed in K-free solution. 3. Intracellular concentrations of K and Na were found to decrease, membrane potential to increase with age. The volume/surface area measured by stereologic and morphometric techniques did not change with age. 4. The permeability coefficient for K (PK), calculated from the absolute K flux and the measured membrane potentials, was fairly constant for a given age between 2-5 and 20 mM-Ko. In K-free solution, PK was markedly reduced (factor 4). At a given Ko, PK increased twofold between 6-8 and 18-20 days while PNa remained relatively constant.", "contents": "Developmental aspects of potassium flux and permeability of the embryonic chick heart. 1. The rate coefficient of 42K efflux, the transmembrane potential, the intracellular concentrations of Na and K and the volume/surface area have been measured in embryonic chick hearts of different ages. 2. With respect to age, the rate coefficient for 42K efflux was minimal for preparations from 6-8 day old embryos, and distinctly higher values were obtained for the hearts of 3-5 and 18-20 days. With respect to the effect of external K concentration (Ko), all age groups showed a five- to sevenfold increase in rate coefficient between 2-5 and 140 mM-Ko. The effect of Ko was found to be indepedent of extracellular Na, except in the 18-20 day hearts bathed in K-free solution. 3. Intracellular concentrations of K and Na were found to decrease, membrane potential to increase with age. The volume/surface area measured by stereologic and morphometric techniques did not change with age. 4. The permeability coefficient for K (PK), calculated from the absolute K flux and the measured membrane potentials, was fairly constant for a given age between 2-5 and 20 mM-Ko. In K-free solution, PK was markedly reduced (factor 4). At a given Ko, PK increased twofold between 6-8 and 18-20 days while PNa remained relatively constant."} {"id": "PMID:1255503", "title": "Effects of atropine, injected into a lateral cerebral ventricle of the rabbit, on fevers due to intravenous leucocyte pyrogen and hypothalamic and intraventricular injections of prostaglandin E1.", "content": "1. Cholinergic synapses in the hypothalamus may transmit information in those thermoregulatory pathways which function to raise body temperature. The effect of atropine, administered intracranially, on the febrile response to intravenous leucocyte pyrogen or intracranial prostaglandin E1 was therefore examined in conscious rabbits. 2. In rabbits exposed to a thermoneutral environment, micro-injections of PGE1, into the anterior hypothalamus, intraventricular injections of PGE1, and intravenous injection so leucocyte pyrogen all caused fever accompanied by vasoconstriction in the ears and reduced respiratory rate. Intraventricular injection of 200 mug atropine during such fevers attenuated their development. This was due to the activation of heat loss mechanisms through vasodilatation in the ears and an increase in the frequency of respiration. This suggests a similarity in the pattern of neuronal activity evoked by PGE1 and leucocyte pyrogen, at least at the site(s) where atropine directly or indirectly exerted its effect and in the efferent pathways from this site. 3. In rabbits exposed to a cold environment, intraventricular injection of PGE1 caused fever through the activation of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shievering and a decrease in O2 consumption so that temperature ceased to rise and returned to normal. 4. During fever, reversal by atropine of the increased heat conservation of rabbits in a neutral environment, and of their increased heat production in a cold environment adds further support to the concept that cholinergic synapses provide an important link in central temperature-rasising pathways.", "contents": "Effects of atropine, injected into a lateral cerebral ventricle of the rabbit, on fevers due to intravenous leucocyte pyrogen and hypothalamic and intraventricular injections of prostaglandin E1. 1. Cholinergic synapses in the hypothalamus may transmit information in those thermoregulatory pathways which function to raise body temperature. The effect of atropine, administered intracranially, on the febrile response to intravenous leucocyte pyrogen or intracranial prostaglandin E1 was therefore examined in conscious rabbits. 2. In rabbits exposed to a thermoneutral environment, micro-injections of PGE1, into the anterior hypothalamus, intraventricular injections of PGE1, and intravenous injection so leucocyte pyrogen all caused fever accompanied by vasoconstriction in the ears and reduced respiratory rate. Intraventricular injection of 200 mug atropine during such fevers attenuated their development. This was due to the activation of heat loss mechanisms through vasodilatation in the ears and an increase in the frequency of respiration. This suggests a similarity in the pattern of neuronal activity evoked by PGE1 and leucocyte pyrogen, at least at the site(s) where atropine directly or indirectly exerted its effect and in the efferent pathways from this site. 3. In rabbits exposed to a cold environment, intraventricular injection of PGE1 caused fever through the activation of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shivering accompanied by increased O2 consumption. Intraventricular injection of atropine during the development of fever caused an inhibition of shievering and a decrease in O2 consumption so that temperature ceased to rise and returned to normal. 4. During fever, reversal by atropine of the increased heat conservation of rabbits in a neutral environment, and of their increased heat production in a cold environment adds further support to the concept that cholinergic synapses provide an important link in central temperature-rasising pathways."} {"id": "PMID:1255504", "title": "The effects of ouabain and ethacrynic acid on the intracellular sodium and potassium concentrations in renal medullary slices incubated in cold potassium-free ringer solution and re-incubated at 37 degrees C in the presence of external potassium.", "content": "1. The cells in slices cut from the renal outer medulla of normally hydrated adult rats were loaded with Na and depleted of K by incubation for up to 100 min in cold iso-osmolal K-free Ringer containing 180 mM-Na. There was a continuous net cellular water loss during this time; an inverse linear relationship existed between water content and intracellular Na concentration. 2. The original intracellular Na and K concentration were restored following 60 min re-incubation in warm Ringer (37 degrees C) containing 5-9 mM-K. Restoration of cellular water content was incomplete after re-incubation for up to 120 min. 3. During incubation in cold K-free Ringer the presence of 1 mM ouabain did not affect cellular Na uptake or K and water loss. Ethacrynic acid, 1 mM, completely blocked cellular Na uptake and water loss, without affecting the intracellular K concentration at 100 min. When ouabain and ethacrynic acid were present together water loss was also prevented but intracellular Na concentration rose slightly by 100 min. 4. During re-incubation in warm K-containing Ringer 1 mM ouabain inhibited Na extrusion completely for up to 60 min while only partially preventing K uptake and further depressing the level of cellular hydration. Ouabain in the presence of 1 mM ethacrynic acid had similar effects on intracellular Na and K concentrations, but raised the level of intracellular water above that of cells in control slices. 5. Ethacrynic acid alone, 1 mM, did not interfere with Na extrusion or K uptake, but also raised intracellular water above control values. 6. The results obtained are discussed in relation to (a) the nature of the preparation used, (b) the possible membrane transport processes occurring and their known or suggested sensitivity to ouabain and ethacrynic acid, (c) the mechanisms which may be responsible for cell volume maintenance in the medulla.", "contents": "The effects of ouabain and ethacrynic acid on the intracellular sodium and potassium concentrations in renal medullary slices incubated in cold potassium-free ringer solution and re-incubated at 37 degrees C in the presence of external potassium. 1. The cells in slices cut from the renal outer medulla of normally hydrated adult rats were loaded with Na and depleted of K by incubation for up to 100 min in cold iso-osmolal K-free Ringer containing 180 mM-Na. There was a continuous net cellular water loss during this time; an inverse linear relationship existed between water content and intracellular Na concentration. 2. The original intracellular Na and K concentration were restored following 60 min re-incubation in warm Ringer (37 degrees C) containing 5-9 mM-K. Restoration of cellular water content was incomplete after re-incubation for up to 120 min. 3. During incubation in cold K-free Ringer the presence of 1 mM ouabain did not affect cellular Na uptake or K and water loss. Ethacrynic acid, 1 mM, completely blocked cellular Na uptake and water loss, without affecting the intracellular K concentration at 100 min. When ouabain and ethacrynic acid were present together water loss was also prevented but intracellular Na concentration rose slightly by 100 min. 4. During re-incubation in warm K-containing Ringer 1 mM ouabain inhibited Na extrusion completely for up to 60 min while only partially preventing K uptake and further depressing the level of cellular hydration. Ouabain in the presence of 1 mM ethacrynic acid had similar effects on intracellular Na and K concentrations, but raised the level of intracellular water above that of cells in control slices. 5. Ethacrynic acid alone, 1 mM, did not interfere with Na extrusion or K uptake, but also raised intracellular water above control values. 6. The results obtained are discussed in relation to (a) the nature of the preparation used, (b) the possible membrane transport processes occurring and their known or suggested sensitivity to ouabain and ethacrynic acid, (c) the mechanisms which may be responsible for cell volume maintenance in the medulla."} {"id": "PMID:1255505", "title": "Isolation of rod and cone contributions to cat ganglion cells by a method of light exchange.", "content": "1. The great majority of cat retinal ganglion cells are known to receive signals from rods and from a single (green) cone type. The centre region of the receptive fields of these cells was stimulated by a spot that changed back and forth from orange to white. By adjusting the intensity of the white spot relative to that of the orange a condition could be established at which the photon-catch rate of the rods remained unchanged during the orange-white exchange. At this intensity setting, termed the rod isolept, rods are thus unstimulated by the exchange, however intense, and the ganglion-cell response was found to be due entirely to the green cones. At another intensity setting of the white spot relative to the orange (cone isolept), the photon catch of the green cones remained unchanged during the exchange and ganglion-cell responses were found to arise entirely from the rods. 2. A neutral wedge in the combined exchange beam (but not in the steady background that covered the whole receptive field) regulated the size of the exchange stimulus and thus the magnitude of the ganglion-cell discharge heard from a loud speaker to the exchange. Exchange threshold was the wedge setting at which this change in firing rate could only just be heard. 3. At the cone isolept, cones remain unstimulated however intense the exchange stimulus, and the rod increment threshold curve was determined over its full range from absolute threshold up to saturation. Likewise, at the rod isolept, the cone increment threshold curve was determined over the same intensity range as for the rods. Rod saturation was found to occur at the point where the cone increment threshold curve began to rise from its absolute threshold level toward its Weber region. 4. The exchange approach also enabled both rod and cone dark-adaptation curves following a strong bleaching exposure to be obtained in the same experiment by moving successively between the cone and rod isolepts. At the cone isolept the time course of early rod dark adaptation could thus be determined when the rod threshold to flashing spots lay well above that of the cones.", "contents": "Isolation of rod and cone contributions to cat ganglion cells by a method of light exchange. 1. The great majority of cat retinal ganglion cells are known to receive signals from rods and from a single (green) cone type. The centre region of the receptive fields of these cells was stimulated by a spot that changed back and forth from orange to white. By adjusting the intensity of the white spot relative to that of the orange a condition could be established at which the photon-catch rate of the rods remained unchanged during the orange-white exchange. At this intensity setting, termed the rod isolept, rods are thus unstimulated by the exchange, however intense, and the ganglion-cell response was found to be due entirely to the green cones. At another intensity setting of the white spot relative to the orange (cone isolept), the photon catch of the green cones remained unchanged during the exchange and ganglion-cell responses were found to arise entirely from the rods. 2. A neutral wedge in the combined exchange beam (but not in the steady background that covered the whole receptive field) regulated the size of the exchange stimulus and thus the magnitude of the ganglion-cell discharge heard from a loud speaker to the exchange. Exchange threshold was the wedge setting at which this change in firing rate could only just be heard. 3. At the cone isolept, cones remain unstimulated however intense the exchange stimulus, and the rod increment threshold curve was determined over its full range from absolute threshold up to saturation. Likewise, at the rod isolept, the cone increment threshold curve was determined over the same intensity range as for the rods. Rod saturation was found to occur at the point where the cone increment threshold curve began to rise from its absolute threshold level toward its Weber region. 4. The exchange approach also enabled both rod and cone dark-adaptation curves following a strong bleaching exposure to be obtained in the same experiment by moving successively between the cone and rod isolepts. At the cone isolept the time course of early rod dark adaptation could thus be determined when the rod threshold to flashing spots lay well above that of the cones."} {"id": "PMID:1255506", "title": "Cancellation of rod signals by cones, and cone signals by rods in the cat retina.", "content": "1. The interaction of rod and cone signals at the level of cat retinal ganglion cells was studied by a method of light exchange. Two spectrally distinct lights were exchanged in such a manner that the rate of photon catch by rods increased in a stepwise manner at the same moment that the cone rate decreased in the same manner, and vice versa. 2. Under any conditions of adaptation, where both rods and cones contributed to the ganglion-cell discharge, it was always possible to adjust the ratio of the magnitudes of the rod and cone stimuli so that no change in ganglion-cell discharge could be detected by listening to the recorded activity via a loudspeaker. We term this condition a silent exchange. 3. On the face of it, the condition of silent exchange arises when rod and cone signals are able to cancel one another, when made opposite in phase by the exchange situation. But was this silence due to a true cancellation of the signals from one photoreceptor type by those of the other type, or was it due to our failure to stimulate the photoreceptors adequately? In order to test whether rod signals can cancel those of cones we bleached both visual pigments and set our exchange apparatus to stimulate the two photoreceptors in the antagonistic manner described above. At first no response could be heard on exchange, for the thresholds of both rods and cones lay above that of our apparatus. But the cones soon recovered and a strong response was heard on exchange. With no change in our stimulating situation, this response diminished with time and silence was again restored. This restoration of silence could not be due to the cones alone, for with time their sensitivity could only further increase. It could only be the increasing sensitivity of the rods that quietened the cone signals. In agreement with this conculsion, the dark-adaptation curve of the rods showed that they became sensitive to our stimulus at the time that the cones began to be silenced. 4. By means of coloured backgrounds we have also shown the converse, namely that rods signals can be cancelled by those of cones.", "contents": "Cancellation of rod signals by cones, and cone signals by rods in the cat retina. 1. The interaction of rod and cone signals at the level of cat retinal ganglion cells was studied by a method of light exchange. Two spectrally distinct lights were exchanged in such a manner that the rate of photon catch by rods increased in a stepwise manner at the same moment that the cone rate decreased in the same manner, and vice versa. 2. Under any conditions of adaptation, where both rods and cones contributed to the ganglion-cell discharge, it was always possible to adjust the ratio of the magnitudes of the rod and cone stimuli so that no change in ganglion-cell discharge could be detected by listening to the recorded activity via a loudspeaker. We term this condition a silent exchange. 3. On the face of it, the condition of silent exchange arises when rod and cone signals are able to cancel one another, when made opposite in phase by the exchange situation. But was this silence due to a true cancellation of the signals from one photoreceptor type by those of the other type, or was it due to our failure to stimulate the photoreceptors adequately? In order to test whether rod signals can cancel those of cones we bleached both visual pigments and set our exchange apparatus to stimulate the two photoreceptors in the antagonistic manner described above. At first no response could be heard on exchange, for the thresholds of both rods and cones lay above that of our apparatus. But the cones soon recovered and a strong response was heard on exchange. With no change in our stimulating situation, this response diminished with time and silence was again restored. This restoration of silence could not be due to the cones alone, for with time their sensitivity could only further increase. It could only be the increasing sensitivity of the rods that quietened the cone signals. In agreement with this conculsion, the dark-adaptation curve of the rods showed that they became sensitive to our stimulus at the time that the cones began to be silenced. 4. By means of coloured backgrounds we have also shown the converse, namely that rods signals can be cancelled by those of cones."} {"id": "PMID:1255507", "title": "The effect of zinc on the late displacement current in squid giant axons.", "content": "1. Displacement currents produced by single depolarizing or hyperpolarizing voltage-clamp pulses (Idepol and Ihyperpol) were recorded from intracellularly perfused squid giant axons treated with tetrodotoxin and tetraethylammonium chloride. The effect of internal Zn on the slow part of the displacement current was studied at different holding potentials. 2. Internal Zn in a concentration of 3-3 mM markedly reduced the slow charge displacement associated with depolarizing and hyperpolarizing pulses. 3. At a holding potential more negative than -60 mV Idepol is normally larger than Ihyperpol if measured with pulses of equal height. The asymmetry Idepol greater than Ihyperpol (which possibly reflects the movement of gating charges) was abolished by Zn. 4. The reversed asymmetry Ihyperpol greater than Idepol which is normally seen at holding potentials less negative than -60 mV was not blocked by Zn. This suggests that the underlying mechanism is different from that of the asymmetry Idepol greater than Ihyperpol. 5. The Zn-sensitive slow charge displacement during single depolarizing pulses was strongly reduced by lowering the holding potential from about -90 to about -30 mV. 6. The observations with single clamp pulses were confirmed by averaging and summing the currents associated with an equal number of depolarizing and hyperpolarizing pulses. 7. The effect of internal Zn on the charge displacement is thought to be due to a reaction with mobile charges in the membrane dielectric. Internal Zn in a concentration of 0-5-1 mM did not significantly shift the Na inactivation curve, indicating that it does not react with surface charges at the inner side of the membrane.", "contents": "The effect of zinc on the late displacement current in squid giant axons. 1. Displacement currents produced by single depolarizing or hyperpolarizing voltage-clamp pulses (Idepol and Ihyperpol) were recorded from intracellularly perfused squid giant axons treated with tetrodotoxin and tetraethylammonium chloride. The effect of internal Zn on the slow part of the displacement current was studied at different holding potentials. 2. Internal Zn in a concentration of 3-3 mM markedly reduced the slow charge displacement associated with depolarizing and hyperpolarizing pulses. 3. At a holding potential more negative than -60 mV Idepol is normally larger than Ihyperpol if measured with pulses of equal height. The asymmetry Idepol greater than Ihyperpol (which possibly reflects the movement of gating charges) was abolished by Zn. 4. The reversed asymmetry Ihyperpol greater than Idepol which is normally seen at holding potentials less negative than -60 mV was not blocked by Zn. This suggests that the underlying mechanism is different from that of the asymmetry Idepol greater than Ihyperpol. 5. The Zn-sensitive slow charge displacement during single depolarizing pulses was strongly reduced by lowering the holding potential from about -90 to about -30 mV. 6. The observations with single clamp pulses were confirmed by averaging and summing the currents associated with an equal number of depolarizing and hyperpolarizing pulses. 7. The effect of internal Zn on the charge displacement is thought to be due to a reaction with mobile charges in the membrane dielectric. Internal Zn in a concentration of 0-5-1 mM did not significantly shift the Na inactivation curve, indicating that it does not react with surface charges at the inner side of the membrane."} {"id": "PMID:1255508", "title": "The effect of acetzolamide on Ion transport across isolated sheep rumen epithelium.", "content": "1. The net fluxes of sodium and chloride from the lumen to the blood side of isolated sheep rumen epithelium were reduced by treatment of both sides of the epithelium with acetazolamide. 2. The changes in the net fluxes of sodium and chloride were significantly correlated and showed recovery after removal of acetazolamide. 3. The net flux of potassium from blood to lumen side of the epithelim was not affected by treatment with acetazolamide. 4. It is suggested that acetazolamide blocks coupled sodium and chloride transport which may be mediated through 'low-activity' carbonic anhydrase enzymes.", "contents": "The effect of acetzolamide on Ion transport across isolated sheep rumen epithelium. 1. The net fluxes of sodium and chloride from the lumen to the blood side of isolated sheep rumen epithelium were reduced by treatment of both sides of the epithelium with acetazolamide. 2. The changes in the net fluxes of sodium and chloride were significantly correlated and showed recovery after removal of acetazolamide. 3. The net flux of potassium from blood to lumen side of the epithelim was not affected by treatment with acetazolamide. 4. It is suggested that acetazolamide blocks coupled sodium and chloride transport which may be mediated through 'low-activity' carbonic anhydrase enzymes."} {"id": "PMID:1255509", "title": "Secretin-like choleretic effect of prostaglandins E1 and E2 in cats.", "content": "1. The effects of intraportal and hepatic arterial infusion of prostaglandins E1 and E2 on liver function and circulation was studied in fasting chloralose anaesthetized cats. 2. Infusion of the prostaglandins at rates of 0-1, 1-0 and 5-0 mug/kg.min caused a 35-40% increase in bile flow. This may be explained by a decrease in the reabsorption or a secretion of sodium ions by the ductular cells. The canalicular bile production and bile flow. This may be explained by a decrease in the reabsorption or a secretion of sodium ions by the ductular cells. The canalicular bile production and bile acid excretion was not affected by the prostaglandins. 3. Infused at rates of 1-0 and 5-0 mug/kg.min the prostaglandins caused a transient decrease in mean arterial blood pressure and mesenteric vascular resistance. The resistance in the intrahepatic arterioles and low-pressure vessels was not affected. 4. The prostaglandins did not influence the splanchnic uptake of oxygen and ethanol, whereas a slight increase in the splanchnic glucose output occurred. 5. The effects of the two prostaglandins were identical and not related to the route of administration.", "contents": "Secretin-like choleretic effect of prostaglandins E1 and E2 in cats. 1. The effects of intraportal and hepatic arterial infusion of prostaglandins E1 and E2 on liver function and circulation was studied in fasting chloralose anaesthetized cats. 2. Infusion of the prostaglandins at rates of 0-1, 1-0 and 5-0 mug/kg.min caused a 35-40% increase in bile flow. This may be explained by a decrease in the reabsorption or a secretion of sodium ions by the ductular cells. The canalicular bile production and bile flow. This may be explained by a decrease in the reabsorption or a secretion of sodium ions by the ductular cells. The canalicular bile production and bile acid excretion was not affected by the prostaglandins. 3. Infused at rates of 1-0 and 5-0 mug/kg.min the prostaglandins caused a transient decrease in mean arterial blood pressure and mesenteric vascular resistance. The resistance in the intrahepatic arterioles and low-pressure vessels was not affected. 4. The prostaglandins did not influence the splanchnic uptake of oxygen and ethanol, whereas a slight increase in the splanchnic glucose output occurred. 5. The effects of the two prostaglandins were identical and not related to the route of administration."} {"id": "PMID:1255510", "title": "Frequency-related inhibitory mechanisms controlling rhythmical activity in the septal area.", "content": "1. The response patterns of identified neurones in the medical and lateral septal regions to varying rates of repetitive stimulation of the fimbria were investigated in rats anaesthetized with urethane. 2. Neurones in the lateral septum which characteristically respond to single pulse stimulation of the fimbria with an activation-inhibition sequence, exhibited a reduction or complete elimination of the inhibitory component both during and following tetanic volleys delivered at 7-12 HZ. Stimulation at lower frequencies did not alter the response. 3. Concurrently with this effect on the inhibitory component of the response exhibited by lateral septal cells, repetitive volleys eliminate the small amplitude burst discharges which are correlated with the onset of the inhibitory period and are considered to indicate the firing of inhibitory interneurones. 4. Tetanic stimulation of the fimbria at rates which eliminate this interneuronal response in the lateral septum, produce an irregular pattern of firing in medial septal neurones which previously exhibited a synchronized bursting discharge to single pulses. 5. Ipsilateral section of the fimbrial input to the septum resulted in the elimination of the burst discharge pattern exhibited by medial septal neurones. 6. The results suggest that a frequency gating mechanism in the lateral septum, activation of which is dependent upon the level of hippocampal output, is responsible for controlling the firing pattern of medical septal neurones.", "contents": "Frequency-related inhibitory mechanisms controlling rhythmical activity in the septal area. 1. The response patterns of identified neurones in the medical and lateral septal regions to varying rates of repetitive stimulation of the fimbria were investigated in rats anaesthetized with urethane. 2. Neurones in the lateral septum which characteristically respond to single pulse stimulation of the fimbria with an activation-inhibition sequence, exhibited a reduction or complete elimination of the inhibitory component both during and following tetanic volleys delivered at 7-12 HZ. Stimulation at lower frequencies did not alter the response. 3. Concurrently with this effect on the inhibitory component of the response exhibited by lateral septal cells, repetitive volleys eliminate the small amplitude burst discharges which are correlated with the onset of the inhibitory period and are considered to indicate the firing of inhibitory interneurones. 4. Tetanic stimulation of the fimbria at rates which eliminate this interneuronal response in the lateral septum, produce an irregular pattern of firing in medial septal neurones which previously exhibited a synchronized bursting discharge to single pulses. 5. Ipsilateral section of the fimbrial input to the septum resulted in the elimination of the burst discharge pattern exhibited by medial septal neurones. 6. The results suggest that a frequency gating mechanism in the lateral septum, activation of which is dependent upon the level of hippocampal output, is responsible for controlling the firing pattern of medical septal neurones."} {"id": "PMID:1255512", "title": "The ionic basis of the resting potential and a slow depolarizing response in Rohon-Beard neurones of Xenopus tadpoles.", "content": "1. Rohon-Beard cells in the spinal cord of Xenopus laevis tadpoles have been studied in animals 4-days to 2-weeks-old (Nieuwkoop & Faber, 1956, stages 45-49). These neurones have an unusually large resting membrane potential of -88 mV, in Ringer solution containing 3-0 mM K+. 2. Their resting potential (R..) depends on the concentration gradient of K+ across the cell membrane. These cells follow the prediction of the Nernst equation for a K+-selective electrode, down to external K+ concentrations as low as 1-0 mM (R.P. -118 mV). 3. The resting potentials of muscle cells in these animals exhibit the same dependence on external [K+], as has been shown previously. 4. Rohon-Beard cells can be driven antidromically, bu stimulation of the anterior end of the spinal cord with brief current pulses through a suction electrode. Antidromic action potentials fail to invade the cell body with repeated stimulation at 1Hz. 5. Even when impulses fail to invade Rohon-Beard somata, slow depolarizations can be produced by single shocks or trains of shocks which cause impulse activity in other neurones. The response can be observed to a single stimulus or to a train of stimuli. The magnitude of the depolarization is graded, depending on the number of stimuli and the frequency of stimulation. 6. Support is presented for the hypothesis that the slow depolarization in Rohon-Beard cells is mediated by the release of K+ into their environment by the impulse activity of neighbouring neurones. The slow depolarization increases in solutions containing 1-5 mM-K+, and decreases in solutions containing 6-0 mM-K+. The changes are in quantitative agreement with those anticipated by theory. 7. The slow depolarization is unlikely to be due to a conductance change produced by a synaptic transmitter, since hyperpolarization and depolarization of the Rohon-Beard cell with injected current do not change the amplitude of the response. Further, low Ca-high Mg solutions which block neuromuscular transmission do not block the response. 8. The possible role of the slow depolarizing response in the physiological activity of these neurones is discussed.", "contents": "The ionic basis of the resting potential and a slow depolarizing response in Rohon-Beard neurones of Xenopus tadpoles. 1. Rohon-Beard cells in the spinal cord of Xenopus laevis tadpoles have been studied in animals 4-days to 2-weeks-old (Nieuwkoop & Faber, 1956, stages 45-49). These neurones have an unusually large resting membrane potential of -88 mV, in Ringer solution containing 3-0 mM K+. 2. Their resting potential (R..) depends on the concentration gradient of K+ across the cell membrane. These cells follow the prediction of the Nernst equation for a K+-selective electrode, down to external K+ concentrations as low as 1-0 mM (R.P. -118 mV). 3. The resting potentials of muscle cells in these animals exhibit the same dependence on external [K+], as has been shown previously. 4. Rohon-Beard cells can be driven antidromically, bu stimulation of the anterior end of the spinal cord with brief current pulses through a suction electrode. Antidromic action potentials fail to invade the cell body with repeated stimulation at 1Hz. 5. Even when impulses fail to invade Rohon-Beard somata, slow depolarizations can be produced by single shocks or trains of shocks which cause impulse activity in other neurones. The response can be observed to a single stimulus or to a train of stimuli. The magnitude of the depolarization is graded, depending on the number of stimuli and the frequency of stimulation. 6. Support is presented for the hypothesis that the slow depolarization in Rohon-Beard cells is mediated by the release of K+ into their environment by the impulse activity of neighbouring neurones. The slow depolarization increases in solutions containing 1-5 mM-K+, and decreases in solutions containing 6-0 mM-K+. The changes are in quantitative agreement with those anticipated by theory. 7. The slow depolarization is unlikely to be due to a conductance change produced by a synaptic transmitter, since hyperpolarization and depolarization of the Rohon-Beard cell with injected current do not change the amplitude of the response. Further, low Ca-high Mg solutions which block neuromuscular transmission do not block the response. 8. The possible role of the slow depolarizing response in the physiological activity of these neurones is discussed."} {"id": "PMID:1255513", "title": "Centrifugal actions on amacrine and ganglion cells in the retina of the turtle.", "content": "1. An electrophysiological investigation of efferent synapses in the retina of the turtle was conducted by recording intracellularly from amacrine cells. These cells have been selected because in birds they have been shown to have direct anatomical connexions with centrifugal fibre terminals. 2. Amacrine cells could be easily distinguished from most other retinal cells, except ganglion cells, by their different photo-responses. Because both amacrine and ganglion cells may generate action potentials they were distinguished by their responses to optic nerve stimulation. 3. The response of ganglion cells to single shock stimulation of the optic nerve consists of an antidromic action potential followed by a late synaptic potential. 4. Cells which did not show antidromic responses but were electrically excitable, by passing direct current through the recording electrode, were considered to be amacrine cells. 5. Amacrine cells generate an e.p.s.p. in response to optic nerve stimulation. An analysis of the e.p.s.p. suggests that it may be due to a single afferent fibre terminating in the proximity of the cell soma. By analogy to the bird, it is concluded that the amacrine cells e.p.s.p.s result from the activation of centrifugal fibres.", "contents": "Centrifugal actions on amacrine and ganglion cells in the retina of the turtle. 1. An electrophysiological investigation of efferent synapses in the retina of the turtle was conducted by recording intracellularly from amacrine cells. These cells have been selected because in birds they have been shown to have direct anatomical connexions with centrifugal fibre terminals. 2. Amacrine cells could be easily distinguished from most other retinal cells, except ganglion cells, by their different photo-responses. Because both amacrine and ganglion cells may generate action potentials they were distinguished by their responses to optic nerve stimulation. 3. The response of ganglion cells to single shock stimulation of the optic nerve consists of an antidromic action potential followed by a late synaptic potential. 4. Cells which did not show antidromic responses but were electrically excitable, by passing direct current through the recording electrode, were considered to be amacrine cells. 5. Amacrine cells generate an e.p.s.p. in response to optic nerve stimulation. An analysis of the e.p.s.p. suggests that it may be due to a single afferent fibre terminating in the proximity of the cell soma. By analogy to the bird, it is concluded that the amacrine cells e.p.s.p.s result from the activation of centrifugal fibres."} {"id": "PMID:1255514", "title": "The temporal and steady-state relationships between activation of the sodium conductance and movement of the gating particles in the squid giant axon.", "content": "1. Comparisons were made between the kinetics and steady-state properties of the sodium conductance changes and of the sodium gating currents, in the squid giant axon perfused with caesium fluoride and maintained at a high membrane holding potential. The conductance measurements were made with reduced external sodium and as much electrical compensation as possible, in order to minimize errors caused by the series resistance. 2. After an initial delay of 10-150 musec whose size was a function of the holding potential and pulse amplitude, the conductance rise on depolarization followed cube law kinetics. 3. Values of the time constant taum, as defined by Hodgkin & Huxley (1952b), were determined for membrane potentials ranging between -140 and +70 mV. They lay on a nearly symmetrical bell-shaped curve with maximum (at 6-3 degrees C) of just under 500 musec at -36 mV. 4. Values of the gating current time constant tau(V) were determined over the same potential range, and found to lie on a very similar bell-shaped curve. A computed least-squares best fit gave the maximum as 460 musec, also falling at about -36 mV. 5. The midpoint of the minfinity curve lay at -34 mV, and its slope at this point was 0-0139 mV-1. Another series of measurements on intact axons gave a midpotential of -25 mV. In the perfused axons the state of the membrane was better described by the constant field equation than by gNa. Recalculation of minfinity from PNa shifted the curve about 15 mV in a positive direction.", "contents": "The temporal and steady-state relationships between activation of the sodium conductance and movement of the gating particles in the squid giant axon. 1. Comparisons were made between the kinetics and steady-state properties of the sodium conductance changes and of the sodium gating currents, in the squid giant axon perfused with caesium fluoride and maintained at a high membrane holding potential. The conductance measurements were made with reduced external sodium and as much electrical compensation as possible, in order to minimize errors caused by the series resistance. 2. After an initial delay of 10-150 musec whose size was a function of the holding potential and pulse amplitude, the conductance rise on depolarization followed cube law kinetics. 3. Values of the time constant taum, as defined by Hodgkin & Huxley (1952b), were determined for membrane potentials ranging between -140 and +70 mV. They lay on a nearly symmetrical bell-shaped curve with maximum (at 6-3 degrees C) of just under 500 musec at -36 mV. 4. Values of the gating current time constant tau(V) were determined over the same potential range, and found to lie on a very similar bell-shaped curve. A computed least-squares best fit gave the maximum as 460 musec, also falling at about -36 mV. 5. The midpoint of the minfinity curve lay at -34 mV, and its slope at this point was 0-0139 mV-1. Another series of measurements on intact axons gave a midpotential of -25 mV. In the perfused axons the state of the membrane was better described by the constant field equation than by gNa. Recalculation of minfinity from PNa shifted the curve about 15 mV in a positive direction."} {"id": "PMID:1255515", "title": "Low resistance junctions between mesoderm cells during development of trunk muscles.", "content": "1. Electrical connexions between mesoderm cells have been examined during the formation of somites in Xenopus laevis, Bombina orientalis and Ambystoma mexicanum. 2. In Xenopus the resting potentials of presumptive myotome cells (-65 + 2 mV, S.E. of mean) and somite muscle cells (-65 +/- 0-6 mV S.E. of mean) were 40 mV, greater than dermatome cells (-25 +/- 0-6 mV, S.E. of mean). Similar differences were found in Bombina and Ambystoma. 3. In all three species cells of the dermatome layer of the mesoderm were electrically coupled to each other. Cells of the presumptive myotome layer in the unsegmented region of the mesoderm were also electrically coupled. 4. In Xenopus dermatome and myotome layers of the mesoderm were not electrically coupled to each other either before or after somite formation. In the other two species dermatome and myotome layers were uncoupled once the somites had formed. 5. In all three species the position of the intersomite border in the unsegmented mesoderm region is marked by the breaking of electrical contracts between those cells destined to form the next somite and the rest of the unsegmented mesoderm. 6. In the axolotl each somite remains electrically insulated from its neighbour. In Xenopus and Bombina electrical connexions are re-established between somite muscle cells once the morphogenetic movements underlying somite formation are complete. 7. Presumptive myotome cells in Xenopus and Ambystoma acquire the membrane property of inward-going rectification before incorporation into a somite. 8. Once Xenopus and Bombina embryos show spontaneous movements large end-plate potentials are recorded from the head somites. Excitation spreads from somite to somite along the low resistance intercellular pathway allowing simultaneous contraction of several somites before extensive somite innervation. 9. The structure of developing somite muscle of Xenopus has been studied with the electron microscope. 10. Close membrane contacts of the gap junction type have been seen between undifferentiated presumptive myotome cells, muscle cells in the same somite and between muscle cells in adjacent somites. 11. Myofilament organization first begins in mesoderm cells when they are forming a new somite. Complete sarcomeres appear in the head somites when the embryo begins spontaneous flexion movements.", "contents": "Low resistance junctions between mesoderm cells during development of trunk muscles. 1. Electrical connexions between mesoderm cells have been examined during the formation of somites in Xenopus laevis, Bombina orientalis and Ambystoma mexicanum. 2. In Xenopus the resting potentials of presumptive myotome cells (-65 + 2 mV, S.E. of mean) and somite muscle cells (-65 +/- 0-6 mV S.E. of mean) were 40 mV, greater than dermatome cells (-25 +/- 0-6 mV, S.E. of mean). Similar differences were found in Bombina and Ambystoma. 3. In all three species cells of the dermatome layer of the mesoderm were electrically coupled to each other. Cells of the presumptive myotome layer in the unsegmented region of the mesoderm were also electrically coupled. 4. In Xenopus dermatome and myotome layers of the mesoderm were not electrically coupled to each other either before or after somite formation. In the other two species dermatome and myotome layers were uncoupled once the somites had formed. 5. In all three species the position of the intersomite border in the unsegmented mesoderm region is marked by the breaking of electrical contracts between those cells destined to form the next somite and the rest of the unsegmented mesoderm. 6. In the axolotl each somite remains electrically insulated from its neighbour. In Xenopus and Bombina electrical connexions are re-established between somite muscle cells once the morphogenetic movements underlying somite formation are complete. 7. Presumptive myotome cells in Xenopus and Ambystoma acquire the membrane property of inward-going rectification before incorporation into a somite. 8. Once Xenopus and Bombina embryos show spontaneous movements large end-plate potentials are recorded from the head somites. Excitation spreads from somite to somite along the low resistance intercellular pathway allowing simultaneous contraction of several somites before extensive somite innervation. 9. The structure of developing somite muscle of Xenopus has been studied with the electron microscope. 10. Close membrane contacts of the gap junction type have been seen between undifferentiated presumptive myotome cells, muscle cells in the same somite and between muscle cells in adjacent somites. 11. Myofilament organization first begins in mesoderm cells when they are forming a new somite. Complete sarcomeres appear in the head somites when the embryo begins spontaneous flexion movements."} {"id": "PMID:1255516", "title": "Alterations in resting membrane properties during neural plate stages of development of the nervous system.", "content": "1. The mean resting membrane potential of cells in the neural plate of axolotl embryos increases from -25 to -45 mV (maximum values from -35 to -60 mV) when the embryos move from early to mid-neural plate stages of development. 2. Increasing the extracellular [K] to 20 mM shortly before the spontaneous increase in resting potential occurs causes neural plate cells to hyperpolarize. 3. A moderate increase in [K]omicron does not hyperpolarize the membrane of neural plate cells at earlier stages or at late neural fold stages. 4. Both the hyperpolarization produced by K and the normal increase in resting potential are blocked by cardiac glycosides. 5. Cells of the ventral ectoderm do not display an increase in resting potential during the neural fold stages of development and do not hyperpolarize in response to a moderate increase in [K]omicron. 6. The results suggest that activation of the Na pump may be an early consequence of neural induction. They are discussed in the light of this suggestion.", "contents": "Alterations in resting membrane properties during neural plate stages of development of the nervous system. 1. The mean resting membrane potential of cells in the neural plate of axolotl embryos increases from -25 to -45 mV (maximum values from -35 to -60 mV) when the embryos move from early to mid-neural plate stages of development. 2. Increasing the extracellular [K] to 20 mM shortly before the spontaneous increase in resting potential occurs causes neural plate cells to hyperpolarize. 3. A moderate increase in [K]omicron does not hyperpolarize the membrane of neural plate cells at earlier stages or at late neural fold stages. 4. Both the hyperpolarization produced by K and the normal increase in resting potential are blocked by cardiac glycosides. 5. Cells of the ventral ectoderm do not display an increase in resting potential during the neural fold stages of development and do not hyperpolarize in response to a moderate increase in [K]omicron. 6. The results suggest that activation of the Na pump may be an early consequence of neural induction. They are discussed in the light of this suggestion."} {"id": "PMID:1255517", "title": "Cortical suppression of the ritino-collicular pathway in the monocularly deprived cat.", "content": "1. In nine cats monocularly deprived from birth, the responses of single neurones in the superior colliculus contralateral to the deprived eye were studied. 2. In six animals most units could be driven by visual stimuli only through the ipsilateral (experienced) eye despite the fact that this colliculus receives a major input from the contralateral (deprived) retina. 3. Immediately following removal of visual cortex, including areas 17, 18 and 19, the collicular units could be driven by the deprived eye. 4. We conclude that the cortex must exert a powerful suppression of the retino-collicular input, and we argue that this suppression occurs in normal as well as in monocularly deprived animals. 5. In three animals the retinal input from the deprived eye was not suppressed but instead dominated many collicular celld, apparently to the exclusion of the cortical input from the experienced eye.", "contents": "Cortical suppression of the ritino-collicular pathway in the monocularly deprived cat. 1. In nine cats monocularly deprived from birth, the responses of single neurones in the superior colliculus contralateral to the deprived eye were studied. 2. In six animals most units could be driven by visual stimuli only through the ipsilateral (experienced) eye despite the fact that this colliculus receives a major input from the contralateral (deprived) retina. 3. Immediately following removal of visual cortex, including areas 17, 18 and 19, the collicular units could be driven by the deprived eye. 4. We conclude that the cortex must exert a powerful suppression of the retino-collicular input, and we argue that this suppression occurs in normal as well as in monocularly deprived animals. 5. In three animals the retinal input from the deprived eye was not suppressed but instead dominated many collicular celld, apparently to the exclusion of the cortical input from the experienced eye."} {"id": "PMID:1255518", "title": "Intercellular coupling in the atrioventricular node and other tissues of the rabbit heart.", "content": "1. A fluorescent tracer dye, sodium fluorescein (mol.wt. 332), was used to assess the relative degree of intercellular coupling in various tissues of the rabbit heart. 2. Dye was injected intracellularly by micro-iontophoresis. Subsequent movement into contiguous cells was monitored by video microscopy. From these data the permeability of the intercellular boundaries was computed. 3. The values of boundary permeability were consistent with those expected from previous studies with tracers whose molecular weights bracketed that of fluorescein. 4. In the atrium, ventricle, Purkinje strands and His bundle, the relative magnitude of the boundary permeability correlated reasonably well with the relative profusity of gap junctional area on the intercalated disk, the latter estimated from published data. 5. The rate of passage of dye between N cells of the atrioventricular, AV, node was at least three orders of magnitude lower than between cells of the other tissues studied; this result is consistent with published reports indicating few gap junctions between cells within the region of slow conduction. 6. Quantitative considerations based on these data indicate that N cells may not be sufficiently well coupled to permit impulse propagation through the AV node by intercellular current flow, alone.", "contents": "Intercellular coupling in the atrioventricular node and other tissues of the rabbit heart. 1. A fluorescent tracer dye, sodium fluorescein (mol.wt. 332), was used to assess the relative degree of intercellular coupling in various tissues of the rabbit heart. 2. Dye was injected intracellularly by micro-iontophoresis. Subsequent movement into contiguous cells was monitored by video microscopy. From these data the permeability of the intercellular boundaries was computed. 3. The values of boundary permeability were consistent with those expected from previous studies with tracers whose molecular weights bracketed that of fluorescein. 4. In the atrium, ventricle, Purkinje strands and His bundle, the relative magnitude of the boundary permeability correlated reasonably well with the relative profusity of gap junctional area on the intercalated disk, the latter estimated from published data. 5. The rate of passage of dye between N cells of the atrioventricular, AV, node was at least three orders of magnitude lower than between cells of the other tissues studied; this result is consistent with published reports indicating few gap junctions between cells within the region of slow conduction. 6. Quantitative considerations based on these data indicate that N cells may not be sufficiently well coupled to permit impulse propagation through the AV node by intercellular current flow, alone."} {"id": "PMID:1255519", "title": "Mode of stimulation by aldosterone of the sodium efflux in barnacle muscle fibres: effects of ouabain, ethacrynic acid, diphenylhydantoin, (ATPMg)(2-), adenine translocase inhibitors, pyruvate and oxythiamine.", "content": "1. A study has been made of the nature of the delayed stimulation caused by external aldosterone in barnacle fibres pre-exposed to aldosterone. 2. (i) Microinjection of 0-5 M-ATPMg2- caused only a small but prompt rise in the Na efflux. (ii) Microinjection of 0-5 M-ATPMg2- followed by external application of 10(-5)M aldosterone greatly augmented the magnitude of the delayed stimulation. The response was dose-dependent, as well as dependent on the concentration of external K+ and H+, but not Na+, Ca2+ or Mg2+. (iii) External application of 10(-5) M aldosterone for 30 min followed by its withdrawal from the bathing medium failed to bring about delayed stimulation. By contrast, fibres into which ATP had been injected showed delayed stimulation under these conditions. 3. Microinjection of actinomycin-D or spironolactone SC-14266 into fibres into which ATP had been injected followed by external application of aldosterone resulted in complete abolition of the delayed stimulation. 4. Delayed stimulation was reduced whether ATP had been injected or not by prior external application of 10(-4)M ouabain or internal application of 8 x 10(-2)M ethacrynic acid. It was completely abolished by prior application of ouabain externally and ethacrynic acid internally, or only 10(-4)M diphenylhydantoin externally. 5. (i) Microinjection of atractyloside or bongkrekic acid caused a substantial fall in the resting Na efflux. Bonkrekic acid proved more powerful than atractyloside. Microinjection of 0-05 M-ATPMg2- into fibres poisoned with 2-0 x 10(-2)M bongkrekic acid completely restored the Na efflux.", "contents": "Mode of stimulation by aldosterone of the sodium efflux in barnacle muscle fibres: effects of ouabain, ethacrynic acid, diphenylhydantoin, (ATPMg)(2-), adenine translocase inhibitors, pyruvate and oxythiamine. 1. A study has been made of the nature of the delayed stimulation caused by external aldosterone in barnacle fibres pre-exposed to aldosterone. 2. (i) Microinjection of 0-5 M-ATPMg2- caused only a small but prompt rise in the Na efflux. (ii) Microinjection of 0-5 M-ATPMg2- followed by external application of 10(-5)M aldosterone greatly augmented the magnitude of the delayed stimulation. The response was dose-dependent, as well as dependent on the concentration of external K+ and H+, but not Na+, Ca2+ or Mg2+. (iii) External application of 10(-5) M aldosterone for 30 min followed by its withdrawal from the bathing medium failed to bring about delayed stimulation. By contrast, fibres into which ATP had been injected showed delayed stimulation under these conditions. 3. Microinjection of actinomycin-D or spironolactone SC-14266 into fibres into which ATP had been injected followed by external application of aldosterone resulted in complete abolition of the delayed stimulation. 4. Delayed stimulation was reduced whether ATP had been injected or not by prior external application of 10(-4)M ouabain or internal application of 8 x 10(-2)M ethacrynic acid. It was completely abolished by prior application of ouabain externally and ethacrynic acid internally, or only 10(-4)M diphenylhydantoin externally. 5. (i) Microinjection of atractyloside or bongkrekic acid caused a substantial fall in the resting Na efflux. Bonkrekic acid proved more powerful than atractyloside. Microinjection of 0-05 M-ATPMg2- into fibres poisoned with 2-0 x 10(-2)M bongkrekic acid completely restored the Na efflux."} {"id": "PMID:1255520", "title": "Lateral geniculate relay of slowly conducting retinal afferents to cat visual cortex.", "content": "1. Lateral geniculate neurones of the cat were studied in terms of the latency for activation by local electrical stimulation of the retina, the latency of electrical activation from the visual cortex and properties of receptive fields. Most of the units were relay cells (antidromic activation from visual cortex) but a small proportion were trans-synaptically activated from the cortex. The latter group included units with on-off, on-centre or off-centra receptive fields. 2. Direct activation of lateral geniculate neurones from local electrical stimulation of retinal ganglion cells or their axons in the retina was identified by the sharpness of timing of the elicited impulses. This procedure revealed the existence of slowly conducting axons relaying in the lateral geniculate nucleus. 3. The distribution of latencies for direct activation from the retina was bimodal with an extended tail of long values. It is similar to the distribution of antidromic latencies of retinal ganglion cells following stimulation of the optic tract. 4. There was a tendency for geniculate neurones with fast input from the retina to have fast axons to the visual cortex and correspondingly for medium-speed and slow input. 5. The previous classification of geniculate receptive fields into sustained and transient types was extended to include commonly encountered 'brisk' and uncommonly encountered 'sluggish' varieties of each. The extension was based on visual properties and latency for direct electrical activation from the retina. Units with receptive fields differing from the familiar on-centre or off-centre concentric pattern were encountered rarely; they included colour-coded fields, local-edge-detectors and one edge-inhibitory off-centre type.", "contents": "Lateral geniculate relay of slowly conducting retinal afferents to cat visual cortex. 1. Lateral geniculate neurones of the cat were studied in terms of the latency for activation by local electrical stimulation of the retina, the latency of electrical activation from the visual cortex and properties of receptive fields. Most of the units were relay cells (antidromic activation from visual cortex) but a small proportion were trans-synaptically activated from the cortex. The latter group included units with on-off, on-centre or off-centra receptive fields. 2. Direct activation of lateral geniculate neurones from local electrical stimulation of retinal ganglion cells or their axons in the retina was identified by the sharpness of timing of the elicited impulses. This procedure revealed the existence of slowly conducting axons relaying in the lateral geniculate nucleus. 3. The distribution of latencies for direct activation from the retina was bimodal with an extended tail of long values. It is similar to the distribution of antidromic latencies of retinal ganglion cells following stimulation of the optic tract. 4. There was a tendency for geniculate neurones with fast input from the retina to have fast axons to the visual cortex and correspondingly for medium-speed and slow input. 5. The previous classification of geniculate receptive fields into sustained and transient types was extended to include commonly encountered 'brisk' and uncommonly encountered 'sluggish' varieties of each. The extension was based on visual properties and latency for direct electrical activation from the retina. Units with receptive fields differing from the familiar on-centre or off-centre concentric pattern were encountered rarely; they included colour-coded fields, local-edge-detectors and one edge-inhibitory off-centre type."} {"id": "PMID:1255521", "title": "Effect of renin-angiotensin system on sodium intake.", "content": "1. Water and saline intake was measured in rats depleted of Na by I.P. dialysis. Na intake was prevented 180 min but not 60-90 min after bilateral nephrectomy. Unilateral nephrectomy as well as ureteral ligature had no effect on Na intake. 2. Renin (3u.) injected I.P. re-established the Na appetite abolished by nephrectomy. 3. Angiotensin I (5 ng) or II (5-40 ng) injected into the 3rd ventricle, also restored the Na intake and this effect was dose-dependent. 4. The angiotensin converting-enzyme inhibitor Sq 20,881 (1 mg/kg) inhibited the effect of AI but not that of AII in restoring Na intake. 5. It is concluded that the kidneys might play a role in the regulation of Na intake through the renin-angiotensin system.", "contents": "Effect of renin-angiotensin system on sodium intake. 1. Water and saline intake was measured in rats depleted of Na by I.P. dialysis. Na intake was prevented 180 min but not 60-90 min after bilateral nephrectomy. Unilateral nephrectomy as well as ureteral ligature had no effect on Na intake. 2. Renin (3u.) injected I.P. re-established the Na appetite abolished by nephrectomy. 3. Angiotensin I (5 ng) or II (5-40 ng) injected into the 3rd ventricle, also restored the Na intake and this effect was dose-dependent. 4. The angiotensin converting-enzyme inhibitor Sq 20,881 (1 mg/kg) inhibited the effect of AI but not that of AII in restoring Na intake. 5. It is concluded that the kidneys might play a role in the regulation of Na intake through the renin-angiotensin system."} {"id": "PMID:1255522", "title": "The physiology and anatomy of long ranging afferent fibres within the spinal cord.", "content": "The caudal extent of the terminal arborizations of dorsal root afferents was determined in adult cats. The method used micro-electrode stimulation within the dorsal horn and the recording on a distant dorsal root filament of the antidromic action potentials evoked by the stimulation of axons within the spinal cord. 2. It was found that all filaments examined in the L2, 3 and 4 dorsal roots contained axons which projected at least as far as the S1 segment. The axons descended in or near the dorsal columns and from there penetrated into the grey matter. 3. The course of single fibres was followed to their apparent terminals. Thresholds, latencies and relative and absolute refractory periods were measured for single axons. These measurements confirmed that continuous axons ran from dorsal roots to distant segments and that the action potentials recorded were not dorsal root reflexes. 4. The majority of fibres with long range central arborizations were shown to have normal receptive fields in the dermatome of their parent dorsal root. They were not aberrant fibres leaving the spinal cord. 5. The long range afferents exist in substantial numbers since fifteen of eighty axons isolated by micro-electrode recording in the L2 dorsal root sent their axons as far as the S1 segment. The presence of these afferents from five segments away does not fit the data published on the inhibitory and excitatory receptive fields or dorsal horn cells which appear adequately explained by afferents arriving over nearby dorsal roots up to two segments away.", "contents": "The physiology and anatomy of long ranging afferent fibres within the spinal cord. The caudal extent of the terminal arborizations of dorsal root afferents was determined in adult cats. The method used micro-electrode stimulation within the dorsal horn and the recording on a distant dorsal root filament of the antidromic action potentials evoked by the stimulation of axons within the spinal cord. 2. It was found that all filaments examined in the L2, 3 and 4 dorsal roots contained axons which projected at least as far as the S1 segment. The axons descended in or near the dorsal columns and from there penetrated into the grey matter. 3. The course of single fibres was followed to their apparent terminals. Thresholds, latencies and relative and absolute refractory periods were measured for single axons. These measurements confirmed that continuous axons ran from dorsal roots to distant segments and that the action potentials recorded were not dorsal root reflexes. 4. The majority of fibres with long range central arborizations were shown to have normal receptive fields in the dermatome of their parent dorsal root. They were not aberrant fibres leaving the spinal cord. 5. The long range afferents exist in substantial numbers since fifteen of eighty axons isolated by micro-electrode recording in the L2 dorsal root sent their axons as far as the S1 segment. The presence of these afferents from five segments away does not fit the data published on the inhibitory and excitatory receptive fields or dorsal horn cells which appear adequately explained by afferents arriving over nearby dorsal roots up to two segments away."} {"id": "PMID:1255523", "title": "Directional differences of impulse spread in trabecular muscle from mammalian heart.", "content": "Trabecular bundles from the right ventricle of calf hearts were used. Electrical properties measured by the application of longitudinal current were compared to those measured by the application of transverse current. 2. The following data were obtained on the basis of classical cable analysis: (i) a ratio of 3-0 for longitudinal to transverse conduction velocity, (ii) a ratio of 3-6 for intra- to extracellular longitudinal resistance, (iii) a ratio of 12-6 for intra- to extracellular transverse resistance, (iv) a ratio of 9-4 for intracellular transverse to intracellular longitudinal resistance, (v) a ratio of 2-7 for the extracellular transverse to the extracellular longitudinal resistance. 3. The disparity in conduction velocity could be explained on the sole grounds of differences in the resistivity of the intracellular and extracellular paths for current flow in the two directions, confirming theoretical predictions. 4. The value of the transverse internal resistance can be accounted for on the ground of frequent branching in a three-dimensional network. There is no need to make the additional assumption of current flow through lateral low resistance pathways between parallel fibres.", "contents": "Directional differences of impulse spread in trabecular muscle from mammalian heart. Trabecular bundles from the right ventricle of calf hearts were used. Electrical properties measured by the application of longitudinal current were compared to those measured by the application of transverse current. 2. The following data were obtained on the basis of classical cable analysis: (i) a ratio of 3-0 for longitudinal to transverse conduction velocity, (ii) a ratio of 3-6 for intra- to extracellular longitudinal resistance, (iii) a ratio of 12-6 for intra- to extracellular transverse resistance, (iv) a ratio of 9-4 for intracellular transverse to intracellular longitudinal resistance, (v) a ratio of 2-7 for the extracellular transverse to the extracellular longitudinal resistance. 3. The disparity in conduction velocity could be explained on the sole grounds of differences in the resistivity of the intracellular and extracellular paths for current flow in the two directions, confirming theoretical predictions. 4. The value of the transverse internal resistance can be accounted for on the ground of frequent branching in a three-dimensional network. There is no need to make the additional assumption of current flow through lateral low resistance pathways between parallel fibres."} {"id": "PMID:1255524", "title": "Ionic currents in the guinea-pig taenia coli.", "content": "Short segments of portions of taenia coli of the guinea-pig averaging 54 mum X 219 mum X ca. 200 mum have been studied by a double sucrose-gap voltage-clamp technique. 2. The average total capacitance was 0-4 muF, corresponding to approximately 10(4) cells, if a specific membrane capacitance of 3 muF/cm2 were assumed. 3. A significant resistance, averaging 11-4omega, was in series with the membrane, and seriously limited the accuracy of the voltage control possible. 4. On depolarization, an early transient inward current was followed by a late maintained outwary current. 5. The late current was carried mainly by K+, because its direction could be reversed if the preparation were first depolarized in isotonic K2SO4 and held back to the original resting potential. 6. After appropriate corrections for residual capacitative and leakage currents, a reversal potential for the late current (Eb) was determined to be 15-20 mV more negative than the natural resting potential. It was not affected by the amplitude or the duration of the activating voltage step, but could be changed by prolonged applications of holding current. 7. At rest, the ratio of PNa:PK was 0-16:1; for Eb it was 0-05:1. 8. The reversal potential for the transient early inward current (Ea) averaged 22 mV in Krebs-bicarbonate solution, but was shifted to about 35 mV when the late current was first suppressed with tetraethylammonium ion. The shift suggested that there was some overlap of the early and late currents. 9. Reduction of [Na+]o to 50% of normal, or replacement of all Na+ with dimethyldiethanol ammonium ion and choline ion, failed to cause any significant shifts in the reversal potential of the early current or reduce the magnitude of the early current. 10. Reduction of [Ca2+]o to 0-25 or 0-1 of the normal caused shifts of the Ea toward the negative and reductions in the early current. These changes can occur without changes in the maximum chord conductance of the early current, such as might happen in ordinary Krebs-bicarbonate solution, or in preparations which had been depolarized by prior treatment with isotonic K2SO4 and then held back to the original membrane voltage. 11. Increase of [Ca2+]o to 5 times normal increased the early inward current, and the maximum chord conductances of the early and late currents, but did not shift the Ea. 12. In preparations pretreated with TEA, increasing [Ca2+]o to 5 times normal shifted Ea toward 45 mV. 13. The various observations are interpreted to mean that the early current in the taenia coli is carried principally by influx of Ca2+, and not by Na+.", "contents": "Ionic currents in the guinea-pig taenia coli. Short segments of portions of taenia coli of the guinea-pig averaging 54 mum X 219 mum X ca. 200 mum have been studied by a double sucrose-gap voltage-clamp technique. 2. The average total capacitance was 0-4 muF, corresponding to approximately 10(4) cells, if a specific membrane capacitance of 3 muF/cm2 were assumed. 3. A significant resistance, averaging 11-4omega, was in series with the membrane, and seriously limited the accuracy of the voltage control possible. 4. On depolarization, an early transient inward current was followed by a late maintained outwary current. 5. The late current was carried mainly by K+, because its direction could be reversed if the preparation were first depolarized in isotonic K2SO4 and held back to the original resting potential. 6. After appropriate corrections for residual capacitative and leakage currents, a reversal potential for the late current (Eb) was determined to be 15-20 mV more negative than the natural resting potential. It was not affected by the amplitude or the duration of the activating voltage step, but could be changed by prolonged applications of holding current. 7. At rest, the ratio of PNa:PK was 0-16:1; for Eb it was 0-05:1. 8. The reversal potential for the transient early inward current (Ea) averaged 22 mV in Krebs-bicarbonate solution, but was shifted to about 35 mV when the late current was first suppressed with tetraethylammonium ion. The shift suggested that there was some overlap of the early and late currents. 9. Reduction of [Na+]o to 50% of normal, or replacement of all Na+ with dimethyldiethanol ammonium ion and choline ion, failed to cause any significant shifts in the reversal potential of the early current or reduce the magnitude of the early current. 10. Reduction of [Ca2+]o to 0-25 or 0-1 of the normal caused shifts of the Ea toward the negative and reductions in the early current. These changes can occur without changes in the maximum chord conductance of the early current, such as might happen in ordinary Krebs-bicarbonate solution, or in preparations which had been depolarized by prior treatment with isotonic K2SO4 and then held back to the original membrane voltage. 11. Increase of [Ca2+]o to 5 times normal increased the early inward current, and the maximum chord conductances of the early and late currents, but did not shift the Ea. 12. In preparations pretreated with TEA, increasing [Ca2+]o to 5 times normal shifted Ea toward 45 mV. 13. The various observations are interpreted to mean that the early current in the taenia coli is carried principally by influx of Ca2+, and not by Na+."} {"id": "PMID:1255525", "title": "Characteristics of the rectifying properties of the sino-atrial node cell of the rabbit.", "content": "After confirming the region of the sino-atrial (S-A) node by its characteristic action potential, man-made strands including the pacemaker region of the rabbit heart were prepared and simple cable theory analysis performed. The estimated gamma was 828 mum in Tyrode. 2. The single sucrose gap method was employed to conduct both the current-clamp experiment and the voltage-clamp experiment. In both methods outward-going and inward-going rectification were observed. 3. The existence of a positive after-potential in the case of the current-clamp experiment and of an outward current tail in the case of the voltage-clamp experiment after cessation of cathodal pulses suggests that the outward-going rectification is due to the increase of K conductance. 4. The slowly developed inward-going rectification was always accompanied with a decrease of membrane resistance. It is unlikely that change in K conductance is solely responsible for this rectification. Discussion was made of the possibility that changes in both Na and Cl conductance together with K conductance might be involved.", "contents": "Characteristics of the rectifying properties of the sino-atrial node cell of the rabbit. After confirming the region of the sino-atrial (S-A) node by its characteristic action potential, man-made strands including the pacemaker region of the rabbit heart were prepared and simple cable theory analysis performed. The estimated gamma was 828 mum in Tyrode. 2. The single sucrose gap method was employed to conduct both the current-clamp experiment and the voltage-clamp experiment. In both methods outward-going and inward-going rectification were observed. 3. The existence of a positive after-potential in the case of the current-clamp experiment and of an outward current tail in the case of the voltage-clamp experiment after cessation of cathodal pulses suggests that the outward-going rectification is due to the increase of K conductance. 4. The slowly developed inward-going rectification was always accompanied with a decrease of membrane resistance. It is unlikely that change in K conductance is solely responsible for this rectification. Discussion was made of the possibility that changes in both Na and Cl conductance together with K conductance might be involved."} {"id": "PMID:1255526", "title": "Lactate metabolism in the isolated perfused rat kidney: relations to renal function and gluconeogenesis.", "content": "In the intact dog, decreases in both glomerular filtration rate and net renal Na+ reabsorption due to raised ureteral pressure were not associated with a decrease in renal lactate oxidation rate, although total renal CO2 production decreased in proportion to the changes in net renal reabsorption of Na+ and glomerular filtration rate. 2. In order to determine whether, in the absence of other added substrates, the metabolism of lactate supports only the 'basal' renal metabolism or can enhance renal function as well, the rate of lactate utilization and decarboxylation by the isolated perfused rat kidney have been quantified in relation to renal function and one measure of renal basal metabolism, glucose production. 3. The perfusate was Krebs-Ringer bicarbonate (pH 7-35-7-48) with Fraction V bovine serum albumin, 6g/100 ml. L-(+)-lactate was added to raise the lactate concentration from endogenous levels to 2-5, 5-0 or 10 mM. 4. We determined: net lactate utilization rate, lactate decarboxylation rate (14CO2 produced from L-(+)-[U-14C]lactate), net glucose production rate, and net re-absorptive rate of Na+. 5. The apparent Km and Vmax for lactate oxidation were 2-1 mM and 1-29 mumole.g-1.min-1 respectively. There was no apparent maximum for total lactate utilization rate due to continuing increases in glucose production rate as lactate concentration was raised. At ca. 10 mM lactate, glucose production accounted for about half of the total lactate utilized. Therefore the basal energy requirements of the kidney need not be constant since glucose production increases as lactate concentration is raised. 6. Both lactate oxidation rate and lactate utilization rate were significantly correlated with the net reabsorption of Na+ by the renal tubules, with the percentage of filtered Na+ reabsorbed and with the glomerular filtration rate. The major fraction of the net renal reabsorption of Na+ was probably supported by the metabolism of substrates either bound to albumin or derived from renal tissue since the percentage of filtered Na+ reabsorbed increased from ca. 78%, when no lactate was added, to 97% when initial lactate concentration was 10 mM. Therefore, addition of lactate increased both the basal mebabolism and tubular function. However, these observations do not permit us to conclude whether it was the presence of lactate, or its utilization by oxidative or by other pathways which enhanced net renal reabsorption of Na+ and the glomerular filtration rate.", "contents": "Lactate metabolism in the isolated perfused rat kidney: relations to renal function and gluconeogenesis. In the intact dog, decreases in both glomerular filtration rate and net renal Na+ reabsorption due to raised ureteral pressure were not associated with a decrease in renal lactate oxidation rate, although total renal CO2 production decreased in proportion to the changes in net renal reabsorption of Na+ and glomerular filtration rate. 2. In order to determine whether, in the absence of other added substrates, the metabolism of lactate supports only the 'basal' renal metabolism or can enhance renal function as well, the rate of lactate utilization and decarboxylation by the isolated perfused rat kidney have been quantified in relation to renal function and one measure of renal basal metabolism, glucose production. 3. The perfusate was Krebs-Ringer bicarbonate (pH 7-35-7-48) with Fraction V bovine serum albumin, 6g/100 ml. L-(+)-lactate was added to raise the lactate concentration from endogenous levels to 2-5, 5-0 or 10 mM. 4. We determined: net lactate utilization rate, lactate decarboxylation rate (14CO2 produced from L-(+)-[U-14C]lactate), net glucose production rate, and net re-absorptive rate of Na+. 5. The apparent Km and Vmax for lactate oxidation were 2-1 mM and 1-29 mumole.g-1.min-1 respectively. There was no apparent maximum for total lactate utilization rate due to continuing increases in glucose production rate as lactate concentration was raised. At ca. 10 mM lactate, glucose production accounted for about half of the total lactate utilized. Therefore the basal energy requirements of the kidney need not be constant since glucose production increases as lactate concentration is raised. 6. Both lactate oxidation rate and lactate utilization rate were significantly correlated with the net reabsorption of Na+ by the renal tubules, with the percentage of filtered Na+ reabsorbed and with the glomerular filtration rate. The major fraction of the net renal reabsorption of Na+ was probably supported by the metabolism of substrates either bound to albumin or derived from renal tissue since the percentage of filtered Na+ reabsorbed increased from ca. 78%, when no lactate was added, to 97% when initial lactate concentration was 10 mM. Therefore, addition of lactate increased both the basal mebabolism and tubular function. However, these observations do not permit us to conclude whether it was the presence of lactate, or its utilization by oxidative or by other pathways which enhanced net renal reabsorption of Na+ and the glomerular filtration rate."} {"id": "PMID:1255527", "title": "Visual cells in the pontine nuclei of the cat.", "content": "Two hundred and thirty-two visually activated neurones were recorded in a small area of the rostral pontine nuclei of cats. The location of visually activated neurones was coextensive with the input from visual areas of cat's cortex as determined by degeneration studies. 2. Pontine visual cells could only be driven by visual stimuli. Cells responsive to somatosensory or auditory stimuli were also found in different regions in rostral pontine nuclei. They too responded to only one modality. 3. 96% of the cells were directionally selective. 4. Pontine visual cells were responsive to a wide range of stimulus speeds. Some cells responded to targets moving as fast as 1000 degrees/sec without losing directional selectivity. No pontine visual cells gave a clearly sustained response to a stationary stimulus. 5. Exact stimulus configurations were not critical. Large fields containing many spots were the most effective stimuli for 50% of the cells. Inhibition of responses depending upon stimulus dimensions, direction of movement, or location in the visual field was found for many cells. 6. Receptive field dimensions were large, ranging in size from 3 degrees X 4 degrees to more than an entire hemifield. 7. 94% of the cells had receptive fields which were centred in the contralateral hemifield. 8. 98% of the cells could be driven from both eyes. 9. The properties of the pontine visual cells suggest a corticopontocerebellar pathway sensitive to a wide range of speeds and directions of movement, but not sensitive to precise form.", "contents": "Visual cells in the pontine nuclei of the cat. Two hundred and thirty-two visually activated neurones were recorded in a small area of the rostral pontine nuclei of cats. The location of visually activated neurones was coextensive with the input from visual areas of cat's cortex as determined by degeneration studies. 2. Pontine visual cells could only be driven by visual stimuli. Cells responsive to somatosensory or auditory stimuli were also found in different regions in rostral pontine nuclei. They too responded to only one modality. 3. 96% of the cells were directionally selective. 4. Pontine visual cells were responsive to a wide range of stimulus speeds. Some cells responded to targets moving as fast as 1000 degrees/sec without losing directional selectivity. No pontine visual cells gave a clearly sustained response to a stationary stimulus. 5. Exact stimulus configurations were not critical. Large fields containing many spots were the most effective stimuli for 50% of the cells. Inhibition of responses depending upon stimulus dimensions, direction of movement, or location in the visual field was found for many cells. 6. Receptive field dimensions were large, ranging in size from 3 degrees X 4 degrees to more than an entire hemifield. 7. 94% of the cells had receptive fields which were centred in the contralateral hemifield. 8. 98% of the cells could be driven from both eyes. 9. The properties of the pontine visual cells suggest a corticopontocerebellar pathway sensitive to a wide range of speeds and directions of movement, but not sensitive to precise form."} {"id": "PMID:1255528", "title": "Two types of extrajunctional L-glutamate receptors in locust muscle fibres.", "content": "L-glutamate applied iontophoretically to the extrajunctional membrane of locust muscle produced a biphasic response, depolarization followed by hyperpolarization (i.e. DH-response). Applying L-glutamate and DL-ibotenate from multibarrel micropipettes allowed comparison of their extrajunctional responses. While glutamate produced a two component response, ibotenate produced a single component H-response. 2. The equilibrium values for the H-responses to L-glutamate and DL-ibotenate applied at the same extrajunctional site were very similar. The equilibrium value was 59-5 +/- 5-4 mV indicating an increased Cl- conductance. The H-response was reversed and abolished in Cl- free medium. Picrotoxin 10(-3) M selectively blocked the H-component of the DH-response in a reversible manner. 3. The possibility that the D- and H-responses arose from the activation of two distinct types of extrajunctional glutamate receptors was investigated. Desensitization of the glutamate H-response by ibotenate and vice versa indicated the presence of an extrajunctional H-receptor sensitive to glutamate and ibotenate and an extrajunctional D-receptor sensitive to glutamate and insensitive to ibotenate. The junctional depolarizing response to glutamate was insensitive to ibotenate. 4. The presence of junctionally occurring H-receptors could not be discounted, although, if present, they were not measurably activated by the excitatory transmitter. 5. Double logarithmic plots (coulomb dose vs. response) for the actions of glutamate and ibotenate on H-receptors had values of 0-75, indicating that both drugs act on the same receptors with similar mechanisms. The value for the action of glutamate on the D-receptors was 1-5. 6. While the extrajunctional D-receptors show analogies to the extrajunctional ACh receptors in vertebrate muscle, the significance of the extrajunctional H-receptors remains speculative.", "contents": "Two types of extrajunctional L-glutamate receptors in locust muscle fibres. L-glutamate applied iontophoretically to the extrajunctional membrane of locust muscle produced a biphasic response, depolarization followed by hyperpolarization (i.e. DH-response). Applying L-glutamate and DL-ibotenate from multibarrel micropipettes allowed comparison of their extrajunctional responses. While glutamate produced a two component response, ibotenate produced a single component H-response. 2. The equilibrium values for the H-responses to L-glutamate and DL-ibotenate applied at the same extrajunctional site were very similar. The equilibrium value was 59-5 +/- 5-4 mV indicating an increased Cl- conductance. The H-response was reversed and abolished in Cl- free medium. Picrotoxin 10(-3) M selectively blocked the H-component of the DH-response in a reversible manner. 3. The possibility that the D- and H-responses arose from the activation of two distinct types of extrajunctional glutamate receptors was investigated. Desensitization of the glutamate H-response by ibotenate and vice versa indicated the presence of an extrajunctional H-receptor sensitive to glutamate and ibotenate and an extrajunctional D-receptor sensitive to glutamate and insensitive to ibotenate. The junctional depolarizing response to glutamate was insensitive to ibotenate. 4. The presence of junctionally occurring H-receptors could not be discounted, although, if present, they were not measurably activated by the excitatory transmitter. 5. Double logarithmic plots (coulomb dose vs. response) for the actions of glutamate and ibotenate on H-receptors had values of 0-75, indicating that both drugs act on the same receptors with similar mechanisms. The value for the action of glutamate on the D-receptors was 1-5. 6. While the extrajunctional D-receptors show analogies to the extrajunctional ACh receptors in vertebrate muscle, the significance of the extrajunctional H-receptors remains speculative."} {"id": "PMID:1255529", "title": "Evidence for carrier-mediated uptake and efflux of sugars at the serosal side of the rat intestinal mucosa in vitro.", "content": "A modification of the everted sac technique is described which allows several sacs to be prepared rapidly and simultaneously from the same segment of rat intestine. 2. A method has been developed for comparing the transport of two sugars by measuring changes in the ratios of their concentrations as they pass across the intestinal wall. 3. With this method significant differences were observed between the D-[3H]galactose and L-[14C]glucose ratios in the mucosal epithelium, the serosal tissue and the serosal compartment. These results indicate that both the efflux of galactose from the serosal side of the mucosal epithelium and the uptake of the sugar into the mucosa are carrier-mediated processes. 4. The mediated efflux of galactose at the serosal side of the epithelial layer is inhibited by the presence of phlorizin on the mucosal side and to some extent by any reduction in the mucosal Na+ concentration. Both of these treatments inhibited galactose uptake at the brush border. Serosal efflux of the sugar appeared to be saturated at high concentrations of D-galactose. 5. Pre-treatment of the sacs with mercuric chloride considerably reduced D-galactose uptake from the luminal side, but did not affect its efflux relative to L-glucose at the serosal side of the mucosal epithelium. 6. Carrier-mediated sugar uptake into the mucosal epithelium from the serosal side was also examined. The role of the bidirectional, carrier-mediated sugar transport processes at the serosal pole of the mucosal epithelial cell in transintestinal transport is discussed.", "contents": "Evidence for carrier-mediated uptake and efflux of sugars at the serosal side of the rat intestinal mucosa in vitro. A modification of the everted sac technique is described which allows several sacs to be prepared rapidly and simultaneously from the same segment of rat intestine. 2. A method has been developed for comparing the transport of two sugars by measuring changes in the ratios of their concentrations as they pass across the intestinal wall. 3. With this method significant differences were observed between the D-[3H]galactose and L-[14C]glucose ratios in the mucosal epithelium, the serosal tissue and the serosal compartment. These results indicate that both the efflux of galactose from the serosal side of the mucosal epithelium and the uptake of the sugar into the mucosa are carrier-mediated processes. 4. The mediated efflux of galactose at the serosal side of the epithelial layer is inhibited by the presence of phlorizin on the mucosal side and to some extent by any reduction in the mucosal Na+ concentration. Both of these treatments inhibited galactose uptake at the brush border. Serosal efflux of the sugar appeared to be saturated at high concentrations of D-galactose. 5. Pre-treatment of the sacs with mercuric chloride considerably reduced D-galactose uptake from the luminal side, but did not affect its efflux relative to L-glucose at the serosal side of the mucosal epithelium. 6. Carrier-mediated sugar uptake into the mucosal epithelium from the serosal side was also examined. The role of the bidirectional, carrier-mediated sugar transport processes at the serosal pole of the mucosal epithelial cell in transintestinal transport is discussed."} {"id": "PMID:1255530", "title": "Comparison of vasoactive intestinal peptide and secretin in stimulation of pancreatic secretion.", "content": "Pancreatic volume flow as well as bicarbonate and protein secretion have been measured in chronic pancreatic fistula cats and dogs in response to I.V. infusion of VIP and secretin or duodenal perfusion of sodium oleate and HCl solution. 2. VIP and secretin infused I.V. in cats produced superimposable pancreatic dose-response curves for volume flow and bicarbonate secretion, reaching almost identical observed and maximal calculated outputs with both peptides. In dogs, VIP was shown previously to be a much less effective stimulant of pancreatic secretion than secretin and the maximal observed bicarbonate output in response to VIP was only about 17% of that to secretin (Konturek, Thor, Dembinski & Kr\u00f3l, 1975). It is condluded that VIP in cats is a secretin-like full agonist, whereas in dogs it is a partial agonist of pancreatic bicarbonate secretion. 3. In cats, secretin and VIP showed equal efficacy and their combination exhibited an augmentatory action on pancreatic bicarbonate secretion with additive kinetics, whereas in dogs, VIP was found to have a lower efficacy than secretin and to inhibit competitively secretin-induced pancreatic secretion. These results might be explained by the interaction of VIP and secretin, two chemically related peptides, on a common receptor site of the exocrine pancreas. 4. Caerulein, an analogue of CCK-PZ, infused I.V. in cats and dogs caused a negligible pancreatic bicarbonate secretion and a potent dose-dependent protein secretion. The combination of graded doses of VIP or secretin with a background dose of caerulein resulted in significantly higher bicarbonate and protein outputs than those induced by VIP or secretin alone. 5. Duodenal perfusion of sodium oleate soap in cats and dogs produced pancreatic dose-response curves for volume flow and bicarbonate output similar to those evoked by VIP in these species. Pancreatic protein secretion in response to luminal oleate was slightly higher than could be accounted for by the action of VIP alone. This might be attributed to the release by oleate not only of endogenous VIP but also CCK-PZ or to the vago-vagal reflexes from gut to pancreas. The results of our combined study on cats and dogs suggest the possibility that oleate releases VIP from the gut and that this peptide may play a physiological role in the stimulation of pancreatic secretion.", "contents": "Comparison of vasoactive intestinal peptide and secretin in stimulation of pancreatic secretion. Pancreatic volume flow as well as bicarbonate and protein secretion have been measured in chronic pancreatic fistula cats and dogs in response to I.V. infusion of VIP and secretin or duodenal perfusion of sodium oleate and HCl solution. 2. VIP and secretin infused I.V. in cats produced superimposable pancreatic dose-response curves for volume flow and bicarbonate secretion, reaching almost identical observed and maximal calculated outputs with both peptides. In dogs, VIP was shown previously to be a much less effective stimulant of pancreatic secretion than secretin and the maximal observed bicarbonate output in response to VIP was only about 17% of that to secretin (Konturek, Thor, Dembinski & Kr\u00f3l, 1975). It is condluded that VIP in cats is a secretin-like full agonist, whereas in dogs it is a partial agonist of pancreatic bicarbonate secretion. 3. In cats, secretin and VIP showed equal efficacy and their combination exhibited an augmentatory action on pancreatic bicarbonate secretion with additive kinetics, whereas in dogs, VIP was found to have a lower efficacy than secretin and to inhibit competitively secretin-induced pancreatic secretion. These results might be explained by the interaction of VIP and secretin, two chemically related peptides, on a common receptor site of the exocrine pancreas. 4. Caerulein, an analogue of CCK-PZ, infused I.V. in cats and dogs caused a negligible pancreatic bicarbonate secretion and a potent dose-dependent protein secretion. The combination of graded doses of VIP or secretin with a background dose of caerulein resulted in significantly higher bicarbonate and protein outputs than those induced by VIP or secretin alone. 5. Duodenal perfusion of sodium oleate soap in cats and dogs produced pancreatic dose-response curves for volume flow and bicarbonate output similar to those evoked by VIP in these species. Pancreatic protein secretion in response to luminal oleate was slightly higher than could be accounted for by the action of VIP alone. This might be attributed to the release by oleate not only of endogenous VIP but also CCK-PZ or to the vago-vagal reflexes from gut to pancreas. The results of our combined study on cats and dogs suggest the possibility that oleate releases VIP from the gut and that this peptide may play a physiological role in the stimulation of pancreatic secretion."} {"id": "PMID:1255531", "title": "Visual cortical cells: their developmental properties in normal and dark reared kittens.", "content": "582 units were recorded in area 17 in twenty-one normally reared kittens, and fourteen dark reared ones, aged between 8 and 42 days. 2. Four classes of neurones were defined: (a) non-activable cells that cannot be excited by any peripheral stimulation; (b) non-specific cells that are sensitive to a visual stimulus moving in any direction; (c) immature cells that are preferentially excited by a rectilinear stimulus but are unselective for its precise orientation; (d) specific cells that appear to be as selective for orientation as the simple or complex cells of the adult cat. 3. 23% of the cells presenting adult characteristics of specificity in terms of directionality and orientation are present in both the normally reared and in the dark reared kittens as soon as the first visual response (12 days) appears. 4. In normally reared kittens the proportion of specific cells increases with age, while that of the non-specific cells decreases. 5. Up to 3 weeks of age there is no significant difference in the proportion of the different types of cells in the dark reared from the normal kittens. But thereafter in the dark reared kittens the specific cells tend to disappear while the non-specific cells increase in number. 6. This confirms the view that cells with some highly specific response properties of the adult visual cortical neurones, especially in relation to orientation specificity, are present in the earliest stages in the absence of all visual experience. However, visual experience is necessary to maintain and develop these specific cells after the third week of post-natal life.", "contents": "Visual cortical cells: their developmental properties in normal and dark reared kittens. 582 units were recorded in area 17 in twenty-one normally reared kittens, and fourteen dark reared ones, aged between 8 and 42 days. 2. Four classes of neurones were defined: (a) non-activable cells that cannot be excited by any peripheral stimulation; (b) non-specific cells that are sensitive to a visual stimulus moving in any direction; (c) immature cells that are preferentially excited by a rectilinear stimulus but are unselective for its precise orientation; (d) specific cells that appear to be as selective for orientation as the simple or complex cells of the adult cat. 3. 23% of the cells presenting adult characteristics of specificity in terms of directionality and orientation are present in both the normally reared and in the dark reared kittens as soon as the first visual response (12 days) appears. 4. In normally reared kittens the proportion of specific cells increases with age, while that of the non-specific cells decreases. 5. Up to 3 weeks of age there is no significant difference in the proportion of the different types of cells in the dark reared from the normal kittens. But thereafter in the dark reared kittens the specific cells tend to disappear while the non-specific cells increase in number. 6. This confirms the view that cells with some highly specific response properties of the adult visual cortical neurones, especially in relation to orientation specificity, are present in the earliest stages in the absence of all visual experience. However, visual experience is necessary to maintain and develop these specific cells after the third week of post-natal life."} {"id": "PMID:1255532", "title": "Absorption from a mixture of seventeen free amino acids by the isolated small intestine of the rat.", "content": "Absorption and secretion from a mixture of seventeen free amino acids has been measured in isolated perfused rat small intestine. 2. The absorption rate of an amino acid from this mixture is proportional to its concentration in the perfusate and independent of its chemical constitution. The constant of proportionality is the same as that previously observed when the perfusate contained peptides as well as amino acids. 3. Amino acids are concentrated, on average, sixfold during passage across the mucosa, and the free amino acid composition of the secretion into the tissue fluid is very similar to that of the luminal perfusate. 4. Peptides do not appear to be added to the tissue fluid during absorption of free amino acids. 5. It is concluded that the mechanisms for absorption of free amino acids are in general independent of those for absorption of peptides.", "contents": "Absorption from a mixture of seventeen free amino acids by the isolated small intestine of the rat. Absorption and secretion from a mixture of seventeen free amino acids has been measured in isolated perfused rat small intestine. 2. The absorption rate of an amino acid from this mixture is proportional to its concentration in the perfusate and independent of its chemical constitution. The constant of proportionality is the same as that previously observed when the perfusate contained peptides as well as amino acids. 3. Amino acids are concentrated, on average, sixfold during passage across the mucosa, and the free amino acid composition of the secretion into the tissue fluid is very similar to that of the luminal perfusate. 4. Peptides do not appear to be added to the tissue fluid during absorption of free amino acids. 5. It is concluded that the mechanisms for absorption of free amino acids are in general independent of those for absorption of peptides."} {"id": "PMID:1255533", "title": "A Markovian model of adult gaze behavior.", "content": "This study was designed to test a proposed Markov chain model of adult gaze behaviors. Hypotheses for an individual's gaze behavior, dyadic visual interaction, and dyadic gaze states within an independent decision model were examined. Subjects were assigned to a same- or mixed-sex dyad and instructed to converse for approximately 5 min about life at the university. Video tapes of the conversations were unobtrusively obtained and scored by an observer of gaze behaviors for 4 1/2 min in 24 pairs of subjects: eight male, eight female, and eight mixed-sex dyads. The results indicate that the occurrence of a gaze behavior is dependent on a 0.6-sec history, but infrequently prolonged Looking behaviors were found to occur slightly more often than Markovian formulations predicted. The mathematical properties of gaze behavior demonstrated in this experiment are congruent with those of dialogic time patterns, suggesting a regularity in the gross temporal organization of nonverbal communications.", "contents": "A Markovian model of adult gaze behavior. This study was designed to test a proposed Markov chain model of adult gaze behaviors. Hypotheses for an individual's gaze behavior, dyadic visual interaction, and dyadic gaze states within an independent decision model were examined. Subjects were assigned to a same- or mixed-sex dyad and instructed to converse for approximately 5 min about life at the university. Video tapes of the conversations were unobtrusively obtained and scored by an observer of gaze behaviors for 4 1/2 min in 24 pairs of subjects: eight male, eight female, and eight mixed-sex dyads. The results indicate that the occurrence of a gaze behavior is dependent on a 0.6-sec history, but infrequently prolonged Looking behaviors were found to occur slightly more often than Markovian formulations predicted. The mathematical properties of gaze behavior demonstrated in this experiment are congruent with those of dialogic time patterns, suggesting a regularity in the gross temporal organization of nonverbal communications."} {"id": "PMID:1255534", "title": "[Double contrast radiography in the study of the gastric posterior wall (author's transl)].", "content": "The authors report their experience about 2,422 examinations with double contrast radiography in the study of the gastric posterior wall. This technique is of great value in the detection, analysis and follow-up of gastric ulcerations. In 54 per cent of cases, the double contrast radiography showed endoscopically proven ulcerations, which where not recognized by standard barium meal technique. The diagnosis of the benign tumours of the posterior wall of the stomach has been also increased bay double contrast radiography. Thus, this technique is recommended for routine examination of the stomach.", "contents": "[Double contrast radiography in the study of the gastric posterior wall (author's transl)]. The authors report their experience about 2,422 examinations with double contrast radiography in the study of the gastric posterior wall. This technique is of great value in the detection, analysis and follow-up of gastric ulcerations. In 54 per cent of cases, the double contrast radiography showed endoscopically proven ulcerations, which where not recognized by standard barium meal technique. The diagnosis of the benign tumours of the posterior wall of the stomach has been also increased bay double contrast radiography. Thus, this technique is recommended for routine examination of the stomach."} {"id": "PMID:1255535", "title": "[Endovascular extraction of catheters after accidental migration into the cardiac cavities (author's transl)].", "content": "The authors describe a technique which permits the extraction of intra-vascular foreign bodies by the intermediary of femoral catheterization. By this method it was possible to extract a catheter below Holter's valve, after accidental migration into the cardiac cavities, in four cases.", "contents": "[Endovascular extraction of catheters after accidental migration into the cardiac cavities (author's transl)]. The authors describe a technique which permits the extraction of intra-vascular foreign bodies by the intermediary of femoral catheterization. By this method it was possible to extract a catheter below Holter's valve, after accidental migration into the cardiac cavities, in four cases."} {"id": "PMID:1255536", "title": "[Presentation of a simple apparatus enabling easier tomography in Hirtz's position (author's transl)].", "content": "By means of a smiple and hardly burdensome apparatus, owing to a tomograph with hypocycloidal or better spiral scanning a detailed study of the boney structures of the base of the skull can be obtained in a position which up to now has been reputed to be difficult.", "contents": "[Presentation of a simple apparatus enabling easier tomography in Hirtz's position (author's transl)]. By means of a smiple and hardly burdensome apparatus, owing to a tomograph with hypocycloidal or better spiral scanning a detailed study of the boney structures of the base of the skull can be obtained in a position which up to now has been reputed to be difficult."} {"id": "PMID:1255537", "title": "[Radiological exploration of alveolar echinococcosis. Concerning two cases with hepatic and splenic localization (author's transl)].", "content": "Two cases of alveolar echinococcosis were observed, the first in a 30 year old man, suffering from a hepatic localization, of the classical icteric and tumoral form, the second in a 26 year old patient, with an exclusively splenic localization, a very exceptional possibility. In both cases, coeliac arteriography showed vascular lesions which led one to suspect the diagnosis. To our knowledge, this is the first case of alveolar echinococcosis explored by arteriography. Furthermore, in the first patient, retrograde catheterization of the biliary tract was carried out, which showed very marked changes of the biliary tract. Inspite of the amount of information provided by the radiological investigations, the diagnosis was not made until the surgical intervention.", "contents": "[Radiological exploration of alveolar echinococcosis. Concerning two cases with hepatic and splenic localization (author's transl)]. Two cases of alveolar echinococcosis were observed, the first in a 30 year old man, suffering from a hepatic localization, of the classical icteric and tumoral form, the second in a 26 year old patient, with an exclusively splenic localization, a very exceptional possibility. In both cases, coeliac arteriography showed vascular lesions which led one to suspect the diagnosis. To our knowledge, this is the first case of alveolar echinococcosis explored by arteriography. Furthermore, in the first patient, retrograde catheterization of the biliary tract was carried out, which showed very marked changes of the biliary tract. Inspite of the amount of information provided by the radiological investigations, the diagnosis was not made until the surgical intervention."} {"id": "PMID:1255538", "title": "[Paget's disease with osseous demineralization (author's transl)].", "content": "Radiological diagnosis of Paget's disease which is based on hypertrophy of the osseous cortex, osteocondensation and a fibrillary appearance of the cancellous bone, can be rendered difficult when there is superadded demineralization. This is usual in the initial phase of the condition and take on the form of circumscribed osteoporosis. Such an appearance can however be misleading owing to its wide extent or to the number of localizations, as was the case in two of our cases; the diagnosis of Paget's disease must then be established from histological criteria. Besides this demineralization which is directly related to the morbid process in Paget's disease, calcium deficiency is known to modify the clinical and radiological symptomatology of Paget's disease. Our first two cases illustrate this fact and the remarkable effectiveness of \"remineralization\" therapy in such cases.", "contents": "[Paget's disease with osseous demineralization (author's transl)]. Radiological diagnosis of Paget's disease which is based on hypertrophy of the osseous cortex, osteocondensation and a fibrillary appearance of the cancellous bone, can be rendered difficult when there is superadded demineralization. This is usual in the initial phase of the condition and take on the form of circumscribed osteoporosis. Such an appearance can however be misleading owing to its wide extent or to the number of localizations, as was the case in two of our cases; the diagnosis of Paget's disease must then be established from histological criteria. Besides this demineralization which is directly related to the morbid process in Paget's disease, calcium deficiency is known to modify the clinical and radiological symptomatology of Paget's disease. Our first two cases illustrate this fact and the remarkable effectiveness of \"remineralization\" therapy in such cases."} {"id": "PMID:1255540", "title": "[A technique of physical modification in mammography (author's transl)].", "content": "The authors propose a technique for use in association with mammography involving aspiration with traction which complements the standard procedure. Traction of the breast makes possible a dynamic study of the organ and its coverings. It may be used in association with radiography, xerography, thermography and transillumination. The changes in the pictures obtained should be compared to other techniques and may be of assistance to the radiologist in their interpretation. An image which does not move is suspicious. An area of translucence around a dense zone, appearing more clearly with traction, is suspicious. Images which do not converge towards the nipple are suspicious. In the light of the information obtained from these new techniques, further examinations may be requested. This simple technique poses no problems for the radiologist and is well accepted by the patient. It provides valuable information contributing to a better approach to diagnosis.", "contents": "[A technique of physical modification in mammography (author's transl)]. The authors propose a technique for use in association with mammography involving aspiration with traction which complements the standard procedure. Traction of the breast makes possible a dynamic study of the organ and its coverings. It may be used in association with radiography, xerography, thermography and transillumination. The changes in the pictures obtained should be compared to other techniques and may be of assistance to the radiologist in their interpretation. An image which does not move is suspicious. An area of translucence around a dense zone, appearing more clearly with traction, is suspicious. Images which do not converge towards the nipple are suspicious. In the light of the information obtained from these new techniques, further examinations may be requested. This simple technique poses no problems for the radiologist and is well accepted by the patient. It provides valuable information contributing to a better approach to diagnosis."} {"id": "PMID:1255541", "title": "[The parietal band. Normal angiographic appearance and its importance in the angiographic investigation of certain congenital cardiac malformations (author's transl)].", "content": "The angiographic study of the parietal band (distal conus) is an important part of the investigation of certain cardiac malformations. In this presentation we have tried to determine the angiographic appearance of the normal parietal band as well as the angiographic aspect of certain conal malformations. Different anomalies of the parietal band may be distinguished: --1) An abnormally developped parietal band may be hypertrophied. 2) The parietal band may be underdevelopped. 3) A well developped parietal band may be in an abnormal position in relation to the interventricular septum. In determining an angiographic relationship between the parietal band, be it normal or abnormal, and the ventricular septal defect, we have tried to establish an angiographic classification of ventricular septal defects.", "contents": "[The parietal band. Normal angiographic appearance and its importance in the angiographic investigation of certain congenital cardiac malformations (author's transl)]. The angiographic study of the parietal band (distal conus) is an important part of the investigation of certain cardiac malformations. In this presentation we have tried to determine the angiographic appearance of the normal parietal band as well as the angiographic aspect of certain conal malformations. Different anomalies of the parietal band may be distinguished: --1) An abnormally developped parietal band may be hypertrophied. 2) The parietal band may be underdevelopped. 3) A well developped parietal band may be in an abnormal position in relation to the interventricular septum. In determining an angiographic relationship between the parietal band, be it normal or abnormal, and the ventricular septal defect, we have tried to establish an angiographic classification of ventricular septal defects."} {"id": "PMID:1255542", "title": "[Usefulness of renal scinitigraphic scanning in the prognosis of acute renal failure (author's transl)].", "content": "The authors present their first results concerning the use of renal scintigraphic scanning using hippuran in acute renal failure (A.R.F.). The tubular stages of hippuran, extraction and secretion then excretion correspond to phenomena which are normally apparent within the first 10 minutes following the injection of hippuran, also it seemed interesting to study the changes which occur in A.R.F. 18 hospital in-patients with A.R.F. were studied, 10 of them suffering from tubulointerstitial nephropathy (T.I.N.) 4 with acute glomerulonephritis (A.G.N.), 2 with obstruction of the urinary pathways and 2 with tubular necrosis on underlying chronic renal failure. In the 10 cases of T.I.N. the phenomenon of extraction was evident without any sign of secretion appearing during the 24 minutes of the investigation. No relationship could be found between the scintigram and the rapidity of recovery from A.R.F., but 8/10 recovered satisfactory renal function, the two others died from their disease, the A.R.F. being only secondary. Two of the 4 cases of A.G.N. had normal or slightly lowered extraction and minimal or absent secretion, and they recovered, in the 2 others no image of extraction appeared within 24 mn. and in these 2 cases the course was unfavorable. Finally, the last four had evident extraction and for 3 of them the course was favorable, the death of the fourth being consecutive to the primary disease. It therefore seems that the presence of an extraction phenomenon, whatever the aetiology of the A.R.F., is a parameter which authorizes the prognosis of a favorable course whereas its absence during the 24 mn. of the investigation permits one to envisage an unfavorable course.", "contents": "[Usefulness of renal scinitigraphic scanning in the prognosis of acute renal failure (author's transl)]. The authors present their first results concerning the use of renal scintigraphic scanning using hippuran in acute renal failure (A.R.F.). The tubular stages of hippuran, extraction and secretion then excretion correspond to phenomena which are normally apparent within the first 10 minutes following the injection of hippuran, also it seemed interesting to study the changes which occur in A.R.F. 18 hospital in-patients with A.R.F. were studied, 10 of them suffering from tubulointerstitial nephropathy (T.I.N.) 4 with acute glomerulonephritis (A.G.N.), 2 with obstruction of the urinary pathways and 2 with tubular necrosis on underlying chronic renal failure. In the 10 cases of T.I.N. the phenomenon of extraction was evident without any sign of secretion appearing during the 24 minutes of the investigation. No relationship could be found between the scintigram and the rapidity of recovery from A.R.F., but 8/10 recovered satisfactory renal function, the two others died from their disease, the A.R.F. being only secondary. Two of the 4 cases of A.G.N. had normal or slightly lowered extraction and minimal or absent secretion, and they recovered, in the 2 others no image of extraction appeared within 24 mn. and in these 2 cases the course was unfavorable. Finally, the last four had evident extraction and for 3 of them the course was favorable, the death of the fourth being consecutive to the primary disease. It therefore seems that the presence of an extraction phenomenon, whatever the aetiology of the A.R.F., is a parameter which authorizes the prognosis of a favorable course whereas its absence during the 24 mn. of the investigation permits one to envisage an unfavorable course."} {"id": "PMID:1255543", "title": "[Angiographic findings in primary miliary hepatic tuberculosis (author's transl)].", "content": "The authors describe the hepatic angiographic findings in two patients with primary miliary hepatic tuberculosis. The main angiographic features are abnormalities of the distal arterioles, with small, nodular and irregular formations. The hepatic and portal veins are normal. To our knowledge, it is the first report of angiographic abnormalities in miliary tuberculosis of the liver. The diagnostic and pronostic interest of these findings are discussed.", "contents": "[Angiographic findings in primary miliary hepatic tuberculosis (author's transl)]. The authors describe the hepatic angiographic findings in two patients with primary miliary hepatic tuberculosis. The main angiographic features are abnormalities of the distal arterioles, with small, nodular and irregular formations. The hepatic and portal veins are normal. To our knowledge, it is the first report of angiographic abnormalities in miliary tuberculosis of the liver. The diagnostic and pronostic interest of these findings are discussed."} {"id": "PMID:1255544", "title": "[A rare cause of antro-pyloric stenosis in the child: septic granulomatosis. Concerning one case (author's transl)].", "content": "Presentation of a case of pyloric stenosis in a five year old boy due to a granuloma during the course of septic granulomatosis. The discussion must enable one to evoke the diagnosis when it is a known case of granulomatous disease, and consequently to treat it medically with antibiotics. In the opposite case where the disease is not known, it is a question of etiological discussion of pyloric stenosis. It is now worth thinking of septic granulomatosis routinely with the more classical causes of pyloric stenosis in the order boy.", "contents": "[A rare cause of antro-pyloric stenosis in the child: septic granulomatosis. Concerning one case (author's transl)]. Presentation of a case of pyloric stenosis in a five year old boy due to a granuloma during the course of septic granulomatosis. The discussion must enable one to evoke the diagnosis when it is a known case of granulomatous disease, and consequently to treat it medically with antibiotics. In the opposite case where the disease is not known, it is a question of etiological discussion of pyloric stenosis. It is now worth thinking of septic granulomatosis routinely with the more classical causes of pyloric stenosis in the order boy."} {"id": "PMID:1255545", "title": "[Osseous and pulmonary sarcoidosis in a 12 year old girl. Radiological study (author's transl)].", "content": "The authors present a rather rare case of sarcoidosis in a 12 year old child. Boney involvement constitutes the first manifestation of the condition, with micro-cystic radiological appearance of the second phalanges of both third fingers. The chest X-ray demonstrated glandular and parenchymatous involvement. The diagnosis was histologically confirmed by osseous biopsy. The authors compare their case with other previously published cases.", "contents": "[Osseous and pulmonary sarcoidosis in a 12 year old girl. Radiological study (author's transl)]. The authors present a rather rare case of sarcoidosis in a 12 year old child. Boney involvement constitutes the first manifestation of the condition, with micro-cystic radiological appearance of the second phalanges of both third fingers. The chest X-ray demonstrated glandular and parenchymatous involvement. The diagnosis was histologically confirmed by osseous biopsy. The authors compare their case with other previously published cases."} {"id": "PMID:1255547", "title": "The paediatric training required by the general practitioner. A report by a Joint Working Party of the British Paediatric Association and the Royal College of General Practitioners.", "content": "This report has been written because special programmes of training for general practice are being developed in many parts of the country and there are questions about the paediatric component of training which need to be discussed nationally.An important part of this report is devoted to listing educational objectives which should be attained in paediatrics by the general practitioner at the end of his training.", "contents": "The paediatric training required by the general practitioner. A report by a Joint Working Party of the British Paediatric Association and the Royal College of General Practitioners. This report has been written because special programmes of training for general practice are being developed in many parts of the country and there are questions about the paediatric component of training which need to be discussed nationally.An important part of this report is devoted to listing educational objectives which should be attained in paediatrics by the general practitioner at the end of his training."} {"id": "PMID:1255548", "title": "Psychotherapy services outside the National Health Service.", "content": "With the help of an Upjohn Travelling Fellowship, I visited 15 units providing services for people under stress. There were nine residential units and six non-residential units, all were Christian charitable organisations and in all there was close co-operation with the medical profession.All these organisations accept referrals from general practitioners and deserve to be more widely known.", "contents": "Psychotherapy services outside the National Health Service. With the help of an Upjohn Travelling Fellowship, I visited 15 units providing services for people under stress. There were nine residential units and six non-residential units, all were Christian charitable organisations and in all there was close co-operation with the medical profession.All these organisations accept referrals from general practitioners and deserve to be more widely known."} {"id": "PMID:1255549", "title": "A general-practice study of the commonest presenting symptoms of alcoholism.", "content": "In general practice alcoholism should be considered when the doctor detects marital disharmony, repeated sickness absenteeism, repeated aggressive behaviour, patients who are in debt, patients in trouble with the Law, patients with frequent upset stomachs for no obvious reason, patients presenting with anxiety and depression, and those who smell of drink.", "contents": "A general-practice study of the commonest presenting symptoms of alcoholism. In general practice alcoholism should be considered when the doctor detects marital disharmony, repeated sickness absenteeism, repeated aggressive behaviour, patients who are in debt, patients in trouble with the Law, patients with frequent upset stomachs for no obvious reason, patients presenting with anxiety and depression, and those who smell of drink."} {"id": "PMID:1255550", "title": "Medical records, medical audit, and community hospitals.", "content": "A survey of community hospitals suggests a need for improving medical records and communications and introducing review procedures. A new and extended system based on an A4 size unit record is described. The benefits of a medical audit procedure in which all general practitioners and senior nurses participate are discussed.", "contents": "Medical records, medical audit, and community hospitals. A survey of community hospitals suggests a need for improving medical records and communications and introducing review procedures. A new and extended system based on an A4 size unit record is described. The benefits of a medical audit procedure in which all general practitioners and senior nurses participate are discussed."} {"id": "PMID:1255551", "title": "Pregnancy in women using intra-uterine contraceptive devices.", "content": "Among 1,041 women fitted with intra-uterine contraceptive devices during a period of 21,445 months there were 51 pregnancies: a rate of 2.9 per hundred women years. Pregnancy occurred most commonly in the young and nulliparous. The importance of the patient checking her device is stressed. Pregnancy occurs most commonly soon after fitting, but may occur at any time. In more than half the cases pregnancy occurred with the device in the uterus. Though most pregnancies were uterine there was a high incidence of ectopic pregnancies. Many pregnancies ended in vaginal delivery, but since the Abortion Act 1967 fewer probably now go to term.", "contents": "Pregnancy in women using intra-uterine contraceptive devices. Among 1,041 women fitted with intra-uterine contraceptive devices during a period of 21,445 months there were 51 pregnancies: a rate of 2.9 per hundred women years. Pregnancy occurred most commonly in the young and nulliparous. The importance of the patient checking her device is stressed. Pregnancy occurs most commonly soon after fitting, but may occur at any time. In more than half the cases pregnancy occurred with the device in the uterus. Though most pregnancies were uterine there was a high incidence of ectopic pregnancies. Many pregnancies ended in vaginal delivery, but since the Abortion Act 1967 fewer probably now go to term."} {"id": "PMID:1255554", "title": "Social work and general practice. A report of a three-year attachment.", "content": "Much has been written about social worker/general-practitioner collaboration, particularly about conflict of roles, differing functions, avenues of accountability, and problems of distributing scarce resources.We suggest that if the two professions are to work more comfortably together, then it is imperative that both also share the despair, hopelessness, anxiety, and anger that are the occupational hazards of each. We suggest ways in which doctors and social workers can look at the pain their patients are suffering to the benefit of the patient and their own working relationship.", "contents": "Social work and general practice. A report of a three-year attachment. Much has been written about social worker/general-practitioner collaboration, particularly about conflict of roles, differing functions, avenues of accountability, and problems of distributing scarce resources.We suggest that if the two professions are to work more comfortably together, then it is imperative that both also share the despair, hopelessness, anxiety, and anger that are the occupational hazards of each. We suggest ways in which doctors and social workers can look at the pain their patients are suffering to the benefit of the patient and their own working relationship."} {"id": "PMID:1255556", "title": "Effect of HCG on the interstitial cells and androgen production in the immature rat testis.", "content": "The effect on the interstitial cells in the immature rat testis of administration of HCG for different periods was correlated with testosterone plasma levels. Significant and progressive stimulation of mitosis was observed after 3 days of HCG treatment but stabilization occurred after 5 days. The numbers of precursor fibroblasts had increased by the 5th day and were still increasing by the 10th day of treatment. Numbers of Leydig cells were significantly greater at 5 and 10 days of treatment. Plasma testosterone showed a progressive and continuous increase in all groups. The increase in Leydig cell number is considered to be due to a combination of increased stimulation of mitoses in Leydig cells and differentiation of precursor fibroblasts. Mitosis seems to precede fibroblastic differentiation, but the latter continues when mitotic changes have stabilized. The elevation of plasma testosterone concentrations is probably due firstly to the stimulation of the existing Leydig cells and then to the increase in the number of hormone-secreting cells.", "contents": "Effect of HCG on the interstitial cells and androgen production in the immature rat testis. The effect on the interstitial cells in the immature rat testis of administration of HCG for different periods was correlated with testosterone plasma levels. Significant and progressive stimulation of mitosis was observed after 3 days of HCG treatment but stabilization occurred after 5 days. The numbers of precursor fibroblasts had increased by the 5th day and were still increasing by the 10th day of treatment. Numbers of Leydig cells were significantly greater at 5 and 10 days of treatment. Plasma testosterone showed a progressive and continuous increase in all groups. The increase in Leydig cell number is considered to be due to a combination of increased stimulation of mitoses in Leydig cells and differentiation of precursor fibroblasts. Mitosis seems to precede fibroblastic differentiation, but the latter continues when mitotic changes have stabilized. The elevation of plasma testosterone concentrations is probably due firstly to the stimulation of the existing Leydig cells and then to the increase in the number of hormone-secreting cells."} {"id": "PMID:1255557", "title": "Effect of gonadotrophins and testosterone on the seminiferous tubules of the immature rat.", "content": "The actions of HCG and PMSG for different periods and of testosterone of the immature rat testis were studied. Short-term administration of HCG (1-3 days) induced an early meiotic and postmeiotic stimulatory effect but a decrease in spermatogonial numbers. Administration of HCG for longer periods (10 days) caused a reduction in numbers of all cell types. Treatment with HCG + PMSG reduced the amount of inhibition, while PMSG alone resulted in histological and humoral signs of stimulation of the interstitial tissue and the meiotic and postmeiotic stages; the numbers of spermatogonia were not affected. Testosterone caused stimulation of the meiotic and postmeiotic stages and a reduced number of spermatogonia. It is concluded that while PMSG directly stimulates spermatogonia, HCG acts through testosterone secretion at the meiotic and postmeiotic stages. The early inhibitory effects of HCG and testosterone on spermatogonial numbers could be ascribed to the inhibition of endogenous FSH by androgens.", "contents": "Effect of gonadotrophins and testosterone on the seminiferous tubules of the immature rat. The actions of HCG and PMSG for different periods and of testosterone of the immature rat testis were studied. Short-term administration of HCG (1-3 days) induced an early meiotic and postmeiotic stimulatory effect but a decrease in spermatogonial numbers. Administration of HCG for longer periods (10 days) caused a reduction in numbers of all cell types. Treatment with HCG + PMSG reduced the amount of inhibition, while PMSG alone resulted in histological and humoral signs of stimulation of the interstitial tissue and the meiotic and postmeiotic stages; the numbers of spermatogonia were not affected. Testosterone caused stimulation of the meiotic and postmeiotic stages and a reduced number of spermatogonia. It is concluded that while PMSG directly stimulates spermatogonia, HCG acts through testosterone secretion at the meiotic and postmeiotic stages. The early inhibitory effects of HCG and testosterone on spermatogonial numbers could be ascribed to the inhibition of endogenous FSH by androgens."} {"id": "PMID:1255558", "title": "Inhibition of bull and rabbit sperm enzymes by alpha-chlorohydrin.", "content": "High concentrations of alpha-chlorohydrin were found to inhibit hyaluronidase, beta-glucuronidase, and aryl sulphatases in bull and rabbit spermatozoa, but not acrosin and neuraminidase. Preincubation of the enzyme and alpha-chlorohydrin was essential to achieve the maximum inhibition which was irreversible.", "contents": "Inhibition of bull and rabbit sperm enzymes by alpha-chlorohydrin. High concentrations of alpha-chlorohydrin were found to inhibit hyaluronidase, beta-glucuronidase, and aryl sulphatases in bull and rabbit spermatozoa, but not acrosin and neuraminidase. Preincubation of the enzyme and alpha-chlorohydrin was essential to achieve the maximum inhibition which was irreversible."} {"id": "PMID:1255559", "title": "The development and proliferation of the trophoblast from ectopic mouse embryo allografts of increasing gestational age.", "content": "The development and proliferation of trophoblast from ectopic mouse embryo allografts and isografts of increasing gestational age in nonimmune and specifically preimmunized hosts was studied. Specific preimmunization of recipients significantly inhibited haemorrhagic nodule development from 3-3 1/2 and 4-4 1/2 day post coitum homozygous blastocysts and from 5-5 1/2 day homozygous egg cylinders. Preimmunization had no effect on the percentage of haemorrhagic nodules which developed from 6-6 1/2 day homozygous egg cylinders. Haemorrhagic nodule development was significantly increased for F1 hybrid allografts compared to homozygous allografts to preimmunized recipients. Coincident with the immune inhibition of haemorrhagic nodule formation was the microscopic finding that in some cases trophoblast cells developed without subsequent proliferation in preimmunized hosts. The results are discussed in relation to the expression of transplantation antigens by the developing conceptus, the continued differentiation of the embryo after transplantation, and the inductive influences of the inner cell mass on trophoblast ontogeny.", "contents": "The development and proliferation of the trophoblast from ectopic mouse embryo allografts of increasing gestational age. The development and proliferation of trophoblast from ectopic mouse embryo allografts and isografts of increasing gestational age in nonimmune and specifically preimmunized hosts was studied. Specific preimmunization of recipients significantly inhibited haemorrhagic nodule development from 3-3 1/2 and 4-4 1/2 day post coitum homozygous blastocysts and from 5-5 1/2 day homozygous egg cylinders. Preimmunization had no effect on the percentage of haemorrhagic nodules which developed from 6-6 1/2 day homozygous egg cylinders. Haemorrhagic nodule development was significantly increased for F1 hybrid allografts compared to homozygous allografts to preimmunized recipients. Coincident with the immune inhibition of haemorrhagic nodule formation was the microscopic finding that in some cases trophoblast cells developed without subsequent proliferation in preimmunized hosts. The results are discussed in relation to the expression of transplantation antigens by the developing conceptus, the continued differentiation of the embryo after transplantation, and the inductive influences of the inner cell mass on trophoblast ontogeny."} {"id": "PMID:1255560", "title": "Progesterone and 20 alpha-dihydroprogesterone in sheep: a model of their distribution and metabolism.", "content": "The rates of metabolism of progesterone and 20alpha-dihydroprogesterone (20alpha-diHP) in sheep have been measured during and after the infusion of tracer amounts of [3H]progesterone. There were significant differences in the blood concentration of [3H]progesterone between experiments, but these were not attributable to the stage of gestation or to the difference between pregnant and non-pregnant animals. The mean (+/- S.E.M.) metabolic clearance rate of progesterone was 3-277 +/- 0-239 litres blood/min. The simplest model of the distribution of progesterone was one containing two pools, V1[P] and V2[P], where [p] is the blood concentration of progesterone, and in 23 experiments on 7 sheep the mean pool dimensions were 7-8[P] mug and 70[P] mug, respectively. This model was developed to include the formation of 20alpha-diHP from progesterone. Progesterone appeared to be the major source of 20alpha-diHP, though this did not seem to be an obligatory metabolite. The parameters obtained gave comparably low residual deviations for both labelled steroids and were consistent with other observations made on progesterone clearance.", "contents": "Progesterone and 20 alpha-dihydroprogesterone in sheep: a model of their distribution and metabolism. The rates of metabolism of progesterone and 20alpha-dihydroprogesterone (20alpha-diHP) in sheep have been measured during and after the infusion of tracer amounts of [3H]progesterone. There were significant differences in the blood concentration of [3H]progesterone between experiments, but these were not attributable to the stage of gestation or to the difference between pregnant and non-pregnant animals. The mean (+/- S.E.M.) metabolic clearance rate of progesterone was 3-277 +/- 0-239 litres blood/min. The simplest model of the distribution of progesterone was one containing two pools, V1[P] and V2[P], where [p] is the blood concentration of progesterone, and in 23 experiments on 7 sheep the mean pool dimensions were 7-8[P] mug and 70[P] mug, respectively. This model was developed to include the formation of 20alpha-diHP from progesterone. Progesterone appeared to be the major source of 20alpha-diHP, though this did not seem to be an obligatory metabolite. The parameters obtained gave comparably low residual deviations for both labelled steroids and were consistent with other observations made on progesterone clearance."} {"id": "PMID:1255561", "title": "The influence of photoperiod on growth and sexual function in male and female collared lemmings (Dicrostonyx groenlandicus).", "content": "The effect of photoperiod on sexual function and growth in weanling male and female collared lemmings (Dicrostonyx groenlandicus) was studied. Males and females maintained in 6 hr light:18 hr dark after weaning were larger at the end of 70 days than their siblings kept in 20L:4D. Males in 6L:18D were longer and overall body growth was greater. Males in 6L:18D had heavier adrenals but there were no differences in the weights of testes, preputial glands or seminal vesicles or in the mean testosterone levels of the two groups. Females in 6L:18D had heavier preputial glands than the 20L:4D females. There were no differences between the two groups in uterine, ovarian or adrenal weights or in the number or mean size of atretic or healthy Graafian follicles. Adult males kept in 6L:18D increased more in body weight than those in 20L:4D, but there was no detectable influence of the short photoperiod on reproductive function.", "contents": "The influence of photoperiod on growth and sexual function in male and female collared lemmings (Dicrostonyx groenlandicus). The effect of photoperiod on sexual function and growth in weanling male and female collared lemmings (Dicrostonyx groenlandicus) was studied. Males and females maintained in 6 hr light:18 hr dark after weaning were larger at the end of 70 days than their siblings kept in 20L:4D. Males in 6L:18D were longer and overall body growth was greater. Males in 6L:18D had heavier adrenals but there were no differences in the weights of testes, preputial glands or seminal vesicles or in the mean testosterone levels of the two groups. Females in 6L:18D had heavier preputial glands than the 20L:4D females. There were no differences between the two groups in uterine, ovarian or adrenal weights or in the number or mean size of atretic or healthy Graafian follicles. Adult males kept in 6L:18D increased more in body weight than those in 20L:4D, but there was no detectable influence of the short photoperiod on reproductive function."} {"id": "PMID:1255562", "title": "Fertility in cows after treatment with a prostaglandin analogue with or without progesterone.", "content": "Two infections each of 500 mug Cloprostenol (ICI-80,996), a synthetic analogue of PGF-2alpha, 11 or 12 days apart or pretreatment for 7 days with progesterone from an intravaginal silastic coil and one injection of 500 mug Cloprostenol were both effective in synchronizing oestrus in heifers or nursing beef cows. After two inseminations at 72 and 96 hr after the end of treatment, the calving rate for cows observed in oestrus after both treatments or for cows that had oestrous-like mucus after the progesterone+Cloprostenol treatment did not differ from that of control cows, but was significantly (P less than 0-025) lower for cows diagnosed as ready for insemination by the characteristics of mucus after the two injections of Cloprostenol. Treated cows disgnosed per rectum as having inactive ovaries had a significantly (P less than 0-005) lower calving rate than those diagnosed as having active ovaries at the start of treatment. Significantly (P less than 0-005) more treated than control cows were inseminated and became pregnant in the first 15 days of the treatment period, but the overall level of reproductive efficiency was low.", "contents": "Fertility in cows after treatment with a prostaglandin analogue with or without progesterone. Two infections each of 500 mug Cloprostenol (ICI-80,996), a synthetic analogue of PGF-2alpha, 11 or 12 days apart or pretreatment for 7 days with progesterone from an intravaginal silastic coil and one injection of 500 mug Cloprostenol were both effective in synchronizing oestrus in heifers or nursing beef cows. After two inseminations at 72 and 96 hr after the end of treatment, the calving rate for cows observed in oestrus after both treatments or for cows that had oestrous-like mucus after the progesterone+Cloprostenol treatment did not differ from that of control cows, but was significantly (P less than 0-025) lower for cows diagnosed as ready for insemination by the characteristics of mucus after the two injections of Cloprostenol. Treated cows disgnosed per rectum as having inactive ovaries had a significantly (P less than 0-005) lower calving rate than those diagnosed as having active ovaries at the start of treatment. Significantly (P less than 0-005) more treated than control cows were inseminated and became pregnant in the first 15 days of the treatment period, but the overall level of reproductive efficiency was low."} {"id": "PMID:1255563", "title": "The distribution of blood flow to the reproductive organs of rats near term.", "content": "The rate of ovarian and utero-placental blood flow through vessels of less than 25 mum diameter was examined with radioactive microspheres in 5 non-pregnant rats and 19 rats at Day 22 of pregnancy. Total blood flow to the reproductive organs was 0-559 ml/min in the non-pregnant animals and 13-2 ml/min in those near term, a 23-fold difference. The mean ovarian blood flow was high and increased from 0-202 ml/min to 0-845 ml/min. Myometrial and endometrial blood flow increased from 0-156 to 2-24 ml/min. The mean maternal placental blood flow at Day 22 of pregnancy was 0-76 ml/min or 121 ml.,min-1 .100 g-1. Litter size was negatively correlated with mean fetal weight but showed little relationship to mean placental weight or to mean maternal placental blood flow.", "contents": "The distribution of blood flow to the reproductive organs of rats near term. The rate of ovarian and utero-placental blood flow through vessels of less than 25 mum diameter was examined with radioactive microspheres in 5 non-pregnant rats and 19 rats at Day 22 of pregnancy. Total blood flow to the reproductive organs was 0-559 ml/min in the non-pregnant animals and 13-2 ml/min in those near term, a 23-fold difference. The mean ovarian blood flow was high and increased from 0-202 ml/min to 0-845 ml/min. Myometrial and endometrial blood flow increased from 0-156 to 2-24 ml/min. The mean maternal placental blood flow at Day 22 of pregnancy was 0-76 ml/min or 121 ml.,min-1 .100 g-1. Litter size was negatively correlated with mean fetal weight but showed little relationship to mean placental weight or to mean maternal placental blood flow."} {"id": "PMID:1255564", "title": "Distribution and development of embryos in the pig.", "content": "The distribution and development of pig embryos were determined in relation to the number of embryos and their positions within the uterine horn between Days 14 and 34 after mating. The observed distribution of 1-11 embryos within a uterine horn was highly correlated (r = 0-96) with the theoretical expected distribution. Embryo spacing was uniform regardless of the number of embryos within the horn. Nitrogen content of the embryo in relation to its position within the uterine horn indicated that development was similar for embryos located at the utero-tubal end or cervical end and comparable to those located in the middle portion of the horm. Placental development, as indicated by nitrogen content, was similar regardless of location within the horn.", "contents": "Distribution and development of embryos in the pig. The distribution and development of pig embryos were determined in relation to the number of embryos and their positions within the uterine horn between Days 14 and 34 after mating. The observed distribution of 1-11 embryos within a uterine horn was highly correlated (r = 0-96) with the theoretical expected distribution. Embryo spacing was uniform regardless of the number of embryos within the horn. Nitrogen content of the embryo in relation to its position within the uterine horn indicated that development was similar for embryos located at the utero-tubal end or cervical end and comparable to those located in the middle portion of the horm. Placental development, as indicated by nitrogen content, was similar regardless of location within the horn."} {"id": "PMID:1255565", "title": "Effect of indomethacin on egg transport and pregnancy in the rabbit.", "content": "Treatment of rabbits with indomethacin (10 mg/kg/day) 48 hr before mating, and with 20 mg/kg at 12 hr followed by 8 mg/kg at 48, 72 or 96 hr after mating did not affect the rate of egg transport through the oviduct. Indomethacin treatment at the time of implantation interfered with pregnancy and caused degeneration and resorption of embryos. These results suggest that inhibition of prostaglandin synthesis does not directly affect egg transport, but that prostaglandin appears to be required for the retention of implanted embryos.", "contents": "Effect of indomethacin on egg transport and pregnancy in the rabbit. Treatment of rabbits with indomethacin (10 mg/kg/day) 48 hr before mating, and with 20 mg/kg at 12 hr followed by 8 mg/kg at 48, 72 or 96 hr after mating did not affect the rate of egg transport through the oviduct. Indomethacin treatment at the time of implantation interfered with pregnancy and caused degeneration and resorption of embryos. These results suggest that inhibition of prostaglandin synthesis does not directly affect egg transport, but that prostaglandin appears to be required for the retention of implanted embryos."} {"id": "PMID:1255566", "title": "Fertilizing ability in vivo and in vitro of spermatozoa of rats and mice treated with alpha-chlorohydrin.", "content": "The fertilizing ability of epididymal spermatozoa from rats and mice treated for 3 or 4 or 9 or 10 days with various doses of alpha-chlorohydrin was tested in vitro, and in vivo by intrauterine insemination. The minimum doses (per kg/day) needed to affect fertilization significantly were: rat, in vitro, 8-8 mg for 3 or 4 days, 4-4 mg for 4 days and 2-7 mg for 9 or 10 days; in vivo, 4-4 mg for 3 or 4 days and 2-7 mg for 9 or 10 days: mouse, in vitro, 4-4 mg for 3 days and 13-3 mg for 9 days; in vivo, 44-2 mg for 3 days and 26-5 for 9 days. Rats were infertile for at least 18 days after receiving 44-2 mg alpha-chlorohydrin/kg/day for 3 days, but fertilizing ability, tested in vivo and in vitro, was restored 10-11 days and 15-18 days, respectively, after daily treatment with 11-1 mg alpha-chlorohydrin/kg for 3 days.", "contents": "Fertilizing ability in vivo and in vitro of spermatozoa of rats and mice treated with alpha-chlorohydrin. The fertilizing ability of epididymal spermatozoa from rats and mice treated for 3 or 4 or 9 or 10 days with various doses of alpha-chlorohydrin was tested in vitro, and in vivo by intrauterine insemination. The minimum doses (per kg/day) needed to affect fertilization significantly were: rat, in vitro, 8-8 mg for 3 or 4 days, 4-4 mg for 4 days and 2-7 mg for 9 or 10 days; in vivo, 4-4 mg for 3 or 4 days and 2-7 mg for 9 or 10 days: mouse, in vitro, 4-4 mg for 3 days and 13-3 mg for 9 days; in vivo, 44-2 mg for 3 days and 26-5 for 9 days. Rats were infertile for at least 18 days after receiving 44-2 mg alpha-chlorohydrin/kg/day for 3 days, but fertilizing ability, tested in vivo and in vitro, was restored 10-11 days and 15-18 days, respectively, after daily treatment with 11-1 mg alpha-chlorohydrin/kg for 3 days."} {"id": "PMID:1255578", "title": "Acceleration of sexual maturation in female rats by male stimulation.", "content": "In comparison to controls reared in isolation, female rats reared in the presence of an adult male from weaning attained puberty 5 days earlier when living in groups or almost 9 days earlier when living singly with a male. Accelerated sexual development occurred in the absence of accelerated physical growth.", "contents": "Acceleration of sexual maturation in female rats by male stimulation. In comparison to controls reared in isolation, female rats reared in the presence of an adult male from weaning attained puberty 5 days earlier when living in groups or almost 9 days earlier when living singly with a male. Accelerated sexual development occurred in the absence of accelerated physical growth."} {"id": "PMID:1255585", "title": "Monoamine oxidase in rat placenta, human placenta, and cultured choriocarcinoma.", "content": "The activity of monoamine oxidase (MAO), an enzyme which metabolized catecholamines and indoleamines, was determined in rat placenta at various stages of gestation, in human term placenta, and in choriocarcinoma grown in culture. From Day 15 to Day 20 of gestation the specific activity (units/mg protein) of MAO in rat placenta increased at least 3-fold; from Day 20 to the time of parturition, it decreased about 50%. The specific activity of MAO in human placenta at term was about 50%. The specific activity of MAO in human placenta at term was about 8 times higher than that of rat placenta at term. No MAO activity was found in choriocarcinoma grown in culture.", "contents": "Monoamine oxidase in rat placenta, human placenta, and cultured choriocarcinoma. The activity of monoamine oxidase (MAO), an enzyme which metabolized catecholamines and indoleamines, was determined in rat placenta at various stages of gestation, in human term placenta, and in choriocarcinoma grown in culture. From Day 15 to Day 20 of gestation the specific activity (units/mg protein) of MAO in rat placenta increased at least 3-fold; from Day 20 to the time of parturition, it decreased about 50%. The specific activity of MAO in human placenta at term was about 50%. The specific activity of MAO in human placenta at term was about 8 times higher than that of rat placenta at term. No MAO activity was found in choriocarcinoma grown in culture."} {"id": "PMID:1255586", "title": "Seasonal changes in the pineal gland related to the reproductive cycle in the male hare, Lepus europaeus.", "content": "During the autumn months, the gonads and reproductive tract of adult male hares (Lepus europaeus) are regressed and circulating gonadotrophin levels are low. At this time the pineal glands are most active as judged by the organ size, and the nuclear and cytoplasmic size of the pinealocytes. There was an inverse relationship between the size of the pineal gland and the weight of the testis, the plasma and testicular testosterone levels, and possibly also the plasma LH levels.", "contents": "Seasonal changes in the pineal gland related to the reproductive cycle in the male hare, Lepus europaeus. During the autumn months, the gonads and reproductive tract of adult male hares (Lepus europaeus) are regressed and circulating gonadotrophin levels are low. At this time the pineal glands are most active as judged by the organ size, and the nuclear and cytoplasmic size of the pinealocytes. There was an inverse relationship between the size of the pineal gland and the weight of the testis, the plasma and testicular testosterone levels, and possibly also the plasma LH levels."} {"id": "PMID:1255639", "title": "Patient acceptance of nurse-midwife in a private group practice.", "content": "Forty private obstetrical patients cared for by a group practice employing a nurse-midwife were interviewed. Half of the study group accepted the nurse-midwife for delivery. The other 20 were delivered by an obstetrician. Acceptance of prenatal care by the nurse-midwife was found to be favorable. Patients reported feeling more comfortable with the nurse-midwife and perceived her as more understanding, sympathetic and available to answer questions than the physicians. The initial encounter with the nurse-midwife differed significantly between those in the two delivery groups. Patients accepting the nurse-midwife for delivery were more likely to have first met her alone while those who chose to be delivered by an obstetrician-gynecologist were more likely to have been introduced to the nurse-midwife by the physician. The implications of this initial \"imprinting experience\" on the acceptance of the nurse-midwife for delivery are discussed.", "contents": "Patient acceptance of nurse-midwife in a private group practice. Forty private obstetrical patients cared for by a group practice employing a nurse-midwife were interviewed. Half of the study group accepted the nurse-midwife for delivery. The other 20 were delivered by an obstetrician. Acceptance of prenatal care by the nurse-midwife was found to be favorable. Patients reported feeling more comfortable with the nurse-midwife and perceived her as more understanding, sympathetic and available to answer questions than the physicians. The initial encounter with the nurse-midwife differed significantly between those in the two delivery groups. Patients accepting the nurse-midwife for delivery were more likely to have first met her alone while those who chose to be delivered by an obstetrician-gynecologist were more likely to have been introduced to the nurse-midwife by the physician. The implications of this initial \"imprinting experience\" on the acceptance of the nurse-midwife for delivery are discussed."} {"id": "PMID:1255640", "title": "Coloscopy clinic: an evaluation of 500 new patients.", "content": "Among the many responsibilities of the gynecologist in modern practice is the detection of neoplasia at the earliest possible opportunity. The advances made in the field of cytology as related to the practice of gynecology are well known and have significantly changed the detection of cervical carcinoma. The resurgence of colposcopy in the evaluation of patients with abnormal cervical cytology has added valuable new dimensions in the understanding of early cervical neoplasia and our ability to diagnose and treat these lesions. The complete acceptance of colposcopy as an essential step in the study of such patients requires a re-education and alteration in the philosophy of management which has been prevalent in American gynecologic practice to date.", "contents": "Coloscopy clinic: an evaluation of 500 new patients. Among the many responsibilities of the gynecologist in modern practice is the detection of neoplasia at the earliest possible opportunity. The advances made in the field of cytology as related to the practice of gynecology are well known and have significantly changed the detection of cervical carcinoma. The resurgence of colposcopy in the evaluation of patients with abnormal cervical cytology has added valuable new dimensions in the understanding of early cervical neoplasia and our ability to diagnose and treat these lesions. The complete acceptance of colposcopy as an essential step in the study of such patients requires a re-education and alteration in the philosophy of management which has been prevalent in American gynecologic practice to date."} {"id": "PMID:1255641", "title": "Intravenous alcohol -- a single blind study in the prevention of premature delivery: a preliminary report.", "content": "A single blind study for the evaluation of intravenous ethanol in the prevention of premature delivery is reported. Randomly selected patients admitted to Tripler General Hospital with uncomplicated pregnancies between 24 and 36 weeks' gestation having regular, sustained contractions were evaluated. Therapy consisted of intravenous 5% ethanol in 5% dextrose/water according to a weight-time-dose schedule. Control patients were given conventional treatment. Statistical evaluation of data has shown no significant difference between success and failure between the study and control groups to date.", "contents": "Intravenous alcohol -- a single blind study in the prevention of premature delivery: a preliminary report. A single blind study for the evaluation of intravenous ethanol in the prevention of premature delivery is reported. Randomly selected patients admitted to Tripler General Hospital with uncomplicated pregnancies between 24 and 36 weeks' gestation having regular, sustained contractions were evaluated. Therapy consisted of intravenous 5% ethanol in 5% dextrose/water according to a weight-time-dose schedule. Control patients were given conventional treatment. Statistical evaluation of data has shown no significant difference between success and failure between the study and control groups to date."} {"id": "PMID:1255642", "title": "Leukocyte alkaline phosphate determinations and urinary estriol excretion in normal and pathologic pregnancies.", "content": "A comparison of the results of two assays for monitoring fetal well-being in normal and pathologic pregnancies is described. Concomitant leukocyte alkaline phosphatase (LAP) score determinations and 24-hour urinary estriol excretion were preformed in the same groups of pregnant women from the 31st week of pregnancy onward. There were 45 women with normal pregnancies, 10 women with antepartum death, 8 women in whom the membranes ruptured at least 30 hours before the determination, 40 women with moderate or severe preeclampsia and 26 women with postmaturity. Determination of LAP score is an easy, rapid and inexpensive method which can be performed in every laboratory. The results are as reliable as estriol determination. Thus LAP score may serve as a valuable method for evaluation of fetal well-being.", "contents": "Leukocyte alkaline phosphate determinations and urinary estriol excretion in normal and pathologic pregnancies. A comparison of the results of two assays for monitoring fetal well-being in normal and pathologic pregnancies is described. Concomitant leukocyte alkaline phosphatase (LAP) score determinations and 24-hour urinary estriol excretion were preformed in the same groups of pregnant women from the 31st week of pregnancy onward. There were 45 women with normal pregnancies, 10 women with antepartum death, 8 women in whom the membranes ruptured at least 30 hours before the determination, 40 women with moderate or severe preeclampsia and 26 women with postmaturity. Determination of LAP score is an easy, rapid and inexpensive method which can be performed in every laboratory. The results are as reliable as estriol determination. Thus LAP score may serve as a valuable method for evaluation of fetal well-being."} {"id": "PMID:1255643", "title": "The pill and the breast.", "content": "Estrogen and progesterone, although of a synthetic type in contraceptive pills, play a major role in the development, growth and function of the breasts. There is no statistically valid evidence to indicate that the widespread use of estrogens for contraceptive purposes and for the menopausal syndrome has increased the incidence of benign, premalignant or malignant breast lesions. However, if a cancer is present in a woman's breast, estrogen can increase its rate of growth. Furthermore, while the effect of exogenous estrogen administration to the population as a whole may be null, there may be a subgroup in which their use may have different effects, with a possible increase in breast cancer incidence in nulliparous or late parous women and a decrease in those with early parity. Patients with a dominant lump, suspicious diagnostic aid changes, serous, serosanguineous, bloody or watery nipple discharge or other adverse breast changes should not receive exogenous estrogens unless the lesion is found to be completely benign on biopsy. Even then, patients with gross cystic disease will continue to have these changes as long as estrogens are administered, and so they should avoid the use of estrogens. Patients in the high rist group for developing breast cancer should be cautioned about the potential dangers of the use of estrogens, whether in birth control pills or in other preparations for the menopause, and if they use them, these patients should be followed carefully by breast self-examinations, periodic examinations by physicians and diagnostic aids. Finally, serious consideration should be given to the inclusion of estriol in all estrogen preparations for its impeding or blocking effect against the potential carcinogenic properties of estradiol and estrone and to the addition of progesterone for its estrogen-antagonistic effect.", "contents": "The pill and the breast. Estrogen and progesterone, although of a synthetic type in contraceptive pills, play a major role in the development, growth and function of the breasts. There is no statistically valid evidence to indicate that the widespread use of estrogens for contraceptive purposes and for the menopausal syndrome has increased the incidence of benign, premalignant or malignant breast lesions. However, if a cancer is present in a woman's breast, estrogen can increase its rate of growth. Furthermore, while the effect of exogenous estrogen administration to the population as a whole may be null, there may be a subgroup in which their use may have different effects, with a possible increase in breast cancer incidence in nulliparous or late parous women and a decrease in those with early parity. Patients with a dominant lump, suspicious diagnostic aid changes, serous, serosanguineous, bloody or watery nipple discharge or other adverse breast changes should not receive exogenous estrogens unless the lesion is found to be completely benign on biopsy. Even then, patients with gross cystic disease will continue to have these changes as long as estrogens are administered, and so they should avoid the use of estrogens. Patients in the high rist group for developing breast cancer should be cautioned about the potential dangers of the use of estrogens, whether in birth control pills or in other preparations for the menopause, and if they use them, these patients should be followed carefully by breast self-examinations, periodic examinations by physicians and diagnostic aids. Finally, serious consideration should be given to the inclusion of estriol in all estrogen preparations for its impeding or blocking effect against the potential carcinogenic properties of estradiol and estrone and to the addition of progesterone for its estrogen-antagonistic effect."} {"id": "PMID:1255646", "title": "The making of a colposcopist. A safe and sensible approach.", "content": "A program was established to determine the accuracy of colposcopy at our institution. Forty-three patients with cytologic or histologic evidence of severe dysplasia or worse underwent diagnostic conization following satisfactory colposcopy. Thirty patients subsequently had either therapeutic conization or hysterectomy preceded by biopsy only. In all 73 cases, the surgical specimen did not reveal a more advanced lesion. However, when the colposcopy was unsatisfactory, the rate of error was 20.8%. It is our opinion that colposcopy is a safe and valuable technique as long as one recognizes the need for training and understands the indications for further diagnostic studies. The use of the colposcope for the evaluation of abnormal cervical cytology has increased steadily over the last few years, and several excellent courses are now offered throughout the United States. Armed with a certificate from such a course, many gynecologists then become self-proclaimed colposcopists in spite of warnings to the contrary by the instructors. In addition, supervision by experienced personnel is not always available. How, then, does one indeed become an accomplished colposcopist to the point that he or she can safely spare the patient the risk, inconvenience and expense of diagnostic cervical conization? Although several recent publications 2,5,6,9,11 document the diagnostic accuracy of colposcopically directly biopsies, we feel each individual should develop and evaluate his or her own skill before altering or abandoning conventional methods of diagnosis and management. The purpose of this report is to present our experience with colposcopy utilizing a program which can perhaps serve as a model to other clinicians.", "contents": "The making of a colposcopist. A safe and sensible approach. A program was established to determine the accuracy of colposcopy at our institution. Forty-three patients with cytologic or histologic evidence of severe dysplasia or worse underwent diagnostic conization following satisfactory colposcopy. Thirty patients subsequently had either therapeutic conization or hysterectomy preceded by biopsy only. In all 73 cases, the surgical specimen did not reveal a more advanced lesion. However, when the colposcopy was unsatisfactory, the rate of error was 20.8%. It is our opinion that colposcopy is a safe and valuable technique as long as one recognizes the need for training and understands the indications for further diagnostic studies. The use of the colposcope for the evaluation of abnormal cervical cytology has increased steadily over the last few years, and several excellent courses are now offered throughout the United States. Armed with a certificate from such a course, many gynecologists then become self-proclaimed colposcopists in spite of warnings to the contrary by the instructors. In addition, supervision by experienced personnel is not always available. How, then, does one indeed become an accomplished colposcopist to the point that he or she can safely spare the patient the risk, inconvenience and expense of diagnostic cervical conization? Although several recent publications 2,5,6,9,11 document the diagnostic accuracy of colposcopically directly biopsies, we feel each individual should develop and evaluate his or her own skill before altering or abandoning conventional methods of diagnosis and management. The purpose of this report is to present our experience with colposcopy utilizing a program which can perhaps serve as a model to other clinicians."} {"id": "PMID:1255647", "title": "The human semen and fertility regulation in the male. International Conference in Andrology.", "content": "An international conference in andrology was held on April 24, 25 and 26, 1975, at the C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan. Eighty-five papers were presented by 165 contributors from Austria, Argentina, Belgium, Canada, Denmark, Finland, France, Germany, Japan, Netherlands, Norway, South africa, Spain, Sweden, Switzerland, Thailand, the United Kingdom and the U.S.A. Eleven sessions of the conference dealt with testicular and epididymal physiology; functional anatomy of spermatozoa; sperm motility and migration; seminal plasma; seminal proteinases and their inhibitors; endocrine-andrology; immunoandrology; neuro-andrology; clinical andrology (diagnostic, endocrine, therapy and surgical); artificial insemination and male contraception.", "contents": "The human semen and fertility regulation in the male. International Conference in Andrology. An international conference in andrology was held on April 24, 25 and 26, 1975, at the C. S. Mott Center for Human Growth and Development, Wayne State University School of Medicine, Detroit, Michigan. Eighty-five papers were presented by 165 contributors from Austria, Argentina, Belgium, Canada, Denmark, Finland, France, Germany, Japan, Netherlands, Norway, South africa, Spain, Sweden, Switzerland, Thailand, the United Kingdom and the U.S.A. Eleven sessions of the conference dealt with testicular and epididymal physiology; functional anatomy of spermatozoa; sperm motility and migration; seminal plasma; seminal proteinases and their inhibitors; endocrine-andrology; immunoandrology; neuro-andrology; clinical andrology (diagnostic, endocrine, therapy and surgical); artificial insemination and male contraception."} {"id": "PMID:1255648", "title": "Incidence of endometriosis in diagnostic laparoscopy.", "content": "Endometriosis is a common finding at laparoscopy. In order to make a correct diagnosis and institute appropriate management it is recommended that laparoscopy be performed on all patients with chronic pelvic pain and on most patients with infertility or acute pelvic pain.", "contents": "Incidence of endometriosis in diagnostic laparoscopy. Endometriosis is a common finding at laparoscopy. In order to make a correct diagnosis and institute appropriate management it is recommended that laparoscopy be performed on all patients with chronic pelvic pain and on most patients with infertility or acute pelvic pain."} {"id": "PMID:1255657", "title": "Synthesis of a potential water-soluble radiographic contrast medium, 2, 4, 6-triiodo-3-acetamido-5-N-methylcarboxamidophenyl beta-D-glucopyranoside.", "content": "Starting from 3,5-dinitrobenzoic acid, the infinitely water-soluble compound, 2, 4, 6-triiodo-3-acetamido-5-N-Methylcarboxamidophenyl Beta-D-glucopyranoside (9), was synthesized in nine steps. Glucoside 9, the first example of potentially a new class of water-soluble x-ray contrast media, is rapidly excreted from dog's plasma into the urine, unchanged. It has low intravenous toxicity in mice (LD50 = 24.5 g/kg). Thin-layer chromatography of aqueous solutions of 9 revealed first appearance of aglycon 7 after 1 week at room temperature.", "contents": "Synthesis of a potential water-soluble radiographic contrast medium, 2, 4, 6-triiodo-3-acetamido-5-N-methylcarboxamidophenyl beta-D-glucopyranoside. Starting from 3,5-dinitrobenzoic acid, the infinitely water-soluble compound, 2, 4, 6-triiodo-3-acetamido-5-N-Methylcarboxamidophenyl Beta-D-glucopyranoside (9), was synthesized in nine steps. Glucoside 9, the first example of potentially a new class of water-soluble x-ray contrast media, is rapidly excreted from dog's plasma into the urine, unchanged. It has low intravenous toxicity in mice (LD50 = 24.5 g/kg). Thin-layer chromatography of aqueous solutions of 9 revealed first appearance of aglycon 7 after 1 week at room temperature."} {"id": "PMID:1255658", "title": "Radiopharmaceuticals. 16. Halogenated dopamine analogs. Synthesis and radiolabeling of 6-iododopamine and tissue distribution studies in animals.", "content": "A simple halogenated derivative of dopamine, 6-iododopamine (1), has been synthesized using two different methods. These synthetic sequences have been applied to the radiolabeling of 1 with carbon-11, iodine-131, and iodine-123. The tissue distribution of 1 in mice, dogs, and rats was determined. The ratio of radioactivity (%/g) in the adrenal medulla-kidney in dogs increases from 3.45 at 2 h postinjection to 33.3 at 24 h postinjection. Thyroid uptakes in mice, dogs, and rats show that in vivo deiodination of 1 is not significant.", "contents": "Radiopharmaceuticals. 16. Halogenated dopamine analogs. Synthesis and radiolabeling of 6-iododopamine and tissue distribution studies in animals. A simple halogenated derivative of dopamine, 6-iododopamine (1), has been synthesized using two different methods. These synthetic sequences have been applied to the radiolabeling of 1 with carbon-11, iodine-131, and iodine-123. The tissue distribution of 1 in mice, dogs, and rats was determined. The ratio of radioactivity (%/g) in the adrenal medulla-kidney in dogs increases from 3.45 at 2 h postinjection to 33.3 at 24 h postinjection. Thyroid uptakes in mice, dogs, and rats show that in vivo deiodination of 1 is not significant."} {"id": "PMID:1255659", "title": "Hypoglycemic alpha-cycloalkylphenylmehtyl, furanalkyl, and thiophenealkyl lactamimides.", "content": "A series of alpha-cycloalkylphenylmethyl lactamimides and a series of furan- and thiophenealkyl lactamimides were prepared for biological evaluation as an extension of earlier finding of hypoglycemic activity in lactamimides. Compounds 7, 20, 23, 25, 29, and 32 produced pronounced hypoglycemia after oral administration to fasted, glucose-primed rats.", "contents": "Hypoglycemic alpha-cycloalkylphenylmehtyl, furanalkyl, and thiophenealkyl lactamimides. A series of alpha-cycloalkylphenylmethyl lactamimides and a series of furan- and thiophenealkyl lactamimides were prepared for biological evaluation as an extension of earlier finding of hypoglycemic activity in lactamimides. Compounds 7, 20, 23, 25, 29, and 32 produced pronounced hypoglycemia after oral administration to fasted, glucose-primed rats."} {"id": "PMID:1255660", "title": "Synthesis and biological activity of camel and bovine beta-melanotropins.", "content": "Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex G-10 and G-25, chromatography on carboxymehtylcellulose, and partition chromatography on Sephadex G-25 with final yields of 56 and 35% for betac2-MSH and betab-MSH, respectively. They were then shown to be identical with their natural hormones in amino acid analysis, paper electrophoresis, disc electrophoresis, thin-layer chromatography, enzymic digests, and bioassays. Bioassay data of these two synthetic melanotropins indicate that the replacement of Ser by Gly in betab-MSH does not change its melanocyte-stimulating activity.", "contents": "Synthesis and biological activity of camel and bovine beta-melanotropins. Two natural occurring melanotropins, camel betaC2-MSH and bovine beta-MSH, have been synthesized by improved solid-phase procedures. The coupling reaction of tert-butyloxycarbonylamino acids was achieved by using their preformed symmetrical anhydrides. The synthetic hormones were purified by gel filtration on Sephadex G-10 and G-25, chromatography on carboxymehtylcellulose, and partition chromatography on Sephadex G-25 with final yields of 56 and 35% for betac2-MSH and betab-MSH, respectively. They were then shown to be identical with their natural hormones in amino acid analysis, paper electrophoresis, disc electrophoresis, thin-layer chromatography, enzymic digests, and bioassays. Bioassay data of these two synthetic melanotropins indicate that the replacement of Ser by Gly in betab-MSH does not change its melanocyte-stimulating activity."} {"id": "PMID:1255661", "title": "Sturcture-activity relationship of daunorubicin and its peptide derivatives.", "content": "The synthesis of potentially specific antitumor peptide derivatives of daunorubicin is presented. The interaction specificites of the drugs with nucleic acids have been examined via stop-flow kinetics as well as the inhibition of DNA template activity. It is found that the biological activity of the daunorubicin derivatives against the mouse P388 tumor is directly proportional to RNA polymerase inhibition and inversely proportional to the rate of dissociation of the DNA complex. It is concluded that the biological efficacy of drugs which act at the replicative and transcriptional level may be estimated by the more rapid in vitro techniques provided that problems of permeability, solubility, stability, etc., in vivo are not encountered.", "contents": "Sturcture-activity relationship of daunorubicin and its peptide derivatives. The synthesis of potentially specific antitumor peptide derivatives of daunorubicin is presented. The interaction specificites of the drugs with nucleic acids have been examined via stop-flow kinetics as well as the inhibition of DNA template activity. It is found that the biological activity of the daunorubicin derivatives against the mouse P388 tumor is directly proportional to RNA polymerase inhibition and inversely proportional to the rate of dissociation of the DNA complex. It is concluded that the biological efficacy of drugs which act at the replicative and transcriptional level may be estimated by the more rapid in vitro techniques provided that problems of permeability, solubility, stability, etc., in vivo are not encountered."} {"id": "PMID:1255662", "title": "Physicochemical and pharmacological studies of some 8-substituted decahydroisoquinolines.", "content": "Several compounds of a diastereoisomeric series of 8-substituted 2-methyldecahydroisoquinolines have been found to be equipotent or more potent than quinidine in prolonging the refractory period of isolated guinea pig atria. The effects of selected compounds on the intracellularly recorded transmembrane action potential of isolated canine Purkinje fibers indicated a mechanism of action similar to quinidine in causing a large decrease in the rising velocity of rapid depolarization. Acid dissociation constants and percentage buccal membrane absorption have been determined, in an attempt to correlate these physiochemical properties and the stereochemistry of the derivatives with the observed antiarrhythmic potency. Compounds with high lipophilicity and the trans ring-juncture stereochemistry generally appear to possess superior potency.", "contents": "Physicochemical and pharmacological studies of some 8-substituted decahydroisoquinolines. Several compounds of a diastereoisomeric series of 8-substituted 2-methyldecahydroisoquinolines have been found to be equipotent or more potent than quinidine in prolonging the refractory period of isolated guinea pig atria. The effects of selected compounds on the intracellularly recorded transmembrane action potential of isolated canine Purkinje fibers indicated a mechanism of action similar to quinidine in causing a large decrease in the rising velocity of rapid depolarization. Acid dissociation constants and percentage buccal membrane absorption have been determined, in an attempt to correlate these physiochemical properties and the stereochemistry of the derivatives with the observed antiarrhythmic potency. Compounds with high lipophilicity and the trans ring-juncture stereochemistry generally appear to possess superior potency."} {"id": "PMID:1255663", "title": "Etodolic acid and related compounds. Chemistry and antiinflammatory actions of some potent di- and trisubstituted 1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids.", "content": "A series of 37 1-ethyl- and 1-n-propyl-1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids bearing one, or two, substituents on the benzene ring has been synthesized via the acid-catalyzed condensation of a substituted tryptophol with ethyl propionylacetate or ethyl butyrylacetate. Antiinflammatory and ulcerogenic effects were examined and the results show that 1, 8-diethyl-1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acid (etodolic acid, USAN) is a potent agent, particularly active against a chronic rat model of inflammation (ED50 0.7 + 1-0.1 mg/kg po in the adjuvant arthritis model) and which has a relatively low acute ulcerogenic potential in the same species.", "contents": "Etodolic acid and related compounds. Chemistry and antiinflammatory actions of some potent di- and trisubstituted 1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids. A series of 37 1-ethyl- and 1-n-propyl-1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acids bearing one, or two, substituents on the benzene ring has been synthesized via the acid-catalyzed condensation of a substituted tryptophol with ethyl propionylacetate or ethyl butyrylacetate. Antiinflammatory and ulcerogenic effects were examined and the results show that 1, 8-diethyl-1, 3, 4, 9-tetrahydropyrano[3, 4-b]indole-1-acetic acid (etodolic acid, USAN) is a potent agent, particularly active against a chronic rat model of inflammation (ED50 0.7 + 1-0.1 mg/kg po in the adjuvant arthritis model) and which has a relatively low acute ulcerogenic potential in the same species."} {"id": "PMID:1255664", "title": "Aminobenzioc acid diuretics. 8.(2) 3, 4-Disubstituted 5-methylsulfonylbenzioc acids and related compounds.", "content": "Various 2, 4- and 3, 4-disubstituted 5-methylsulfonylbenzoic acids were synthesized as methylsulfonyl analogues of previously described 5-sulfamoylbenzoic acid diuretics. The results of the diuretic screening in dogs reveal that substitution of the sulfamoyl group by the spatially and sterically similar methylsulfonyl group does not affect the diuretic pattern but leads generally to somewhat decreased potency. For the highly potent 3-benzylamino-4-phenoxy-5-methylsulfonylbenzoic acid the corresponding 5-methylthio and 5-methylsulfinyl analogs were prepared and found still to exhibit diuretic activity. Internal aldol condensation and subsequent dehydration of 3-benzylamino-and 3-n-butylamino-4-benzoyl-5-methylsulfonylbenzoic acid provided the corresponding inactive 4-alkylamino-6-carboxy-2, 3-dihydro-3-hydroxy-3-phenylbenzo[b]thiophene 1, 1-dioxides and 4-alkylamino-6-carboxy-3-phenyl-benzo[b]thiophene 1,1-dioxides.", "contents": "Aminobenzioc acid diuretics. 8.(2) 3, 4-Disubstituted 5-methylsulfonylbenzioc acids and related compounds. Various 2, 4- and 3, 4-disubstituted 5-methylsulfonylbenzoic acids were synthesized as methylsulfonyl analogues of previously described 5-sulfamoylbenzoic acid diuretics. The results of the diuretic screening in dogs reveal that substitution of the sulfamoyl group by the spatially and sterically similar methylsulfonyl group does not affect the diuretic pattern but leads generally to somewhat decreased potency. For the highly potent 3-benzylamino-4-phenoxy-5-methylsulfonylbenzoic acid the corresponding 5-methylthio and 5-methylsulfinyl analogs were prepared and found still to exhibit diuretic activity. Internal aldol condensation and subsequent dehydration of 3-benzylamino-and 3-n-butylamino-4-benzoyl-5-methylsulfonylbenzoic acid provided the corresponding inactive 4-alkylamino-6-carboxy-2, 3-dihydro-3-hydroxy-3-phenylbenzo[b]thiophene 1, 1-dioxides and 4-alkylamino-6-carboxy-3-phenyl-benzo[b]thiophene 1,1-dioxides."} {"id": "PMID:1255665", "title": "Conformational influence of a 19-methyl substituent in 19-oxygenated steroid structures.", "content": "The crystal and molecular structure of (19R)-19-methyl-5-androstene-3beta, 17beta, 19-triol (C20H32O3) has been determined. The crystals are orthorhombic and the space group is P212121. The unit cell parameters are a =11.179 A, b = 21.485 A, and c = 7.328 A. The structure was solved using the direct methods program MULTAN and refined anisotorpically to an R of 7.2% for all data. The methyl substituent on C(19) is located over the B ring and the hydroxyl between the A and C rings. The flexible B ring has a distorted half-chair conformation. The 19R configuration suggests that the reaction mechanism for the formation of this compound proposed by Wicha and Caspi is incorrect. Furthermore, these results indicate that the stereochemical assignment of C(19) by Skinner and Akhtar resulting from a tritiated sodium borohydride reduction is also suspect.", "contents": "Conformational influence of a 19-methyl substituent in 19-oxygenated steroid structures. The crystal and molecular structure of (19R)-19-methyl-5-androstene-3beta, 17beta, 19-triol (C20H32O3) has been determined. The crystals are orthorhombic and the space group is P212121. The unit cell parameters are a =11.179 A, b = 21.485 A, and c = 7.328 A. The structure was solved using the direct methods program MULTAN and refined anisotorpically to an R of 7.2% for all data. The methyl substituent on C(19) is located over the B ring and the hydroxyl between the A and C rings. The flexible B ring has a distorted half-chair conformation. The 19R configuration suggests that the reaction mechanism for the formation of this compound proposed by Wicha and Caspi is incorrect. Furthermore, these results indicate that the stereochemical assignment of C(19) by Skinner and Akhtar resulting from a tritiated sodium borohydride reduction is also suspect."} {"id": "PMID:1255666", "title": "Contraceptive agents from cycloaddition reactions of diarylcyclopropenones and diarylthiirene 1, 1-dioxides.", "content": "The potential for compounds with antifertility activity from the reactions of diphenylcyclopropernone (1) and 2, 3-diphenylthiirene 1, 1-dioxide (2) with enamines is described. In certain instances, a marked dissociation of antifertility from estrogenic activity was possible. Two series were studied extensively, one was stilbene amides (7) and the other stilbene amino ketones (8). The latter series (8) afforded several materials from which, on further biological work-up, was singled out compound 21 as a potent antifertility agent in rats and hamsters.", "contents": "Contraceptive agents from cycloaddition reactions of diarylcyclopropenones and diarylthiirene 1, 1-dioxides. The potential for compounds with antifertility activity from the reactions of diphenylcyclopropernone (1) and 2, 3-diphenylthiirene 1, 1-dioxide (2) with enamines is described. In certain instances, a marked dissociation of antifertility from estrogenic activity was possible. Two series were studied extensively, one was stilbene amides (7) and the other stilbene amino ketones (8). The latter series (8) afforded several materials from which, on further biological work-up, was singled out compound 21 as a potent antifertility agent in rats and hamsters."} {"id": "PMID:1255667", "title": "Analogs of luteinizing hormone-releasing hormone with increased biological activity produced by D-amino acid substitutions in position 6.", "content": "The incorporation of simple d-amino acids in place of glycine in position 6 of the LH-RH decapeptide produces analogs which have far greater gonadotropin-releasing activities in vivo and in vitro than the natural hormone. An investigation of the structural features of the d-amino acids responsible for this phenomenon suggests that an increase in the lipophilic character and perhaps the size and aromaticity of the side chain coincides with an increase in biological activity. This is demonstrated by the LH-releasing activities of the following series of peptides which were assayed over a period of 6 h in immature male rats: [d-Glu(6)]-,1.8;[d-Ala(6)]-,7.0;[d-Leu(6)]-,9,0;[d-Phe(6)]-,10;[d-Trp(6)]-LH-RH, 13 times more active than LH-RH itself. In contrast to previous results with [d-Ala(6)]-and [d-Leu(6)]-LH-RH, where the substitution of an ethylamide group for the glycine amide at the C-terminus produces large increases in LH/FSH releasing activity, the ethylamide derivatives of [d-Phe(6)]-and [d-Trp(6)]-LH-RH were actually less potent than their parent peptides. [(N-Me-d-Ala)(6)]-LH-RH was found to be approximately 70 times less active than [d-Ala(6)]-LH-RH which indicates that disruption of a preferred receptor-site binding conformation might be brought about by methylation of the amide linkage in this position.", "contents": "Analogs of luteinizing hormone-releasing hormone with increased biological activity produced by D-amino acid substitutions in position 6. The incorporation of simple d-amino acids in place of glycine in position 6 of the LH-RH decapeptide produces analogs which have far greater gonadotropin-releasing activities in vivo and in vitro than the natural hormone. An investigation of the structural features of the d-amino acids responsible for this phenomenon suggests that an increase in the lipophilic character and perhaps the size and aromaticity of the side chain coincides with an increase in biological activity. This is demonstrated by the LH-releasing activities of the following series of peptides which were assayed over a period of 6 h in immature male rats: [d-Glu(6)]-,1.8;[d-Ala(6)]-,7.0;[d-Leu(6)]-,9,0;[d-Phe(6)]-,10;[d-Trp(6)]-LH-RH, 13 times more active than LH-RH itself. In contrast to previous results with [d-Ala(6)]-and [d-Leu(6)]-LH-RH, where the substitution of an ethylamide group for the glycine amide at the C-terminus produces large increases in LH/FSH releasing activity, the ethylamide derivatives of [d-Phe(6)]-and [d-Trp(6)]-LH-RH were actually less potent than their parent peptides. [(N-Me-d-Ala)(6)]-LH-RH was found to be approximately 70 times less active than [d-Ala(6)]-LH-RH which indicates that disruption of a preferred receptor-site binding conformation might be brought about by methylation of the amide linkage in this position."} {"id": "PMID:1255668", "title": "Synthesis of the antileukemic compound N,N(11)-[5-[bis(2-chloroethyl)amino]-1, 3-phenylene]bisurea.", "content": "Conversion of 5-nitro-1, 3-benzenedicarboxylic acid (1) to the diamide 2 followed by hypochlorite rearrangement to the idamine 3 and subsequent reaction with acetic anhydride gave the bisacetamide 4. Reduction to the amine 5 followed by treatment with ethylene oxide formed the diol 6. The latter was converted to the bistosylate 7, which undrewent facile displacement with lithium chloride in acetone to give the mustard 8. Removal of the acetyl groups with hydrochloric acid gave 9, which reacted with potassium cyanate to provide the bisurea 10. In an alternative, but less satisfactory synthesis of 10, the compound (5-nitro-1, 3-phenylene) biscarbamic acid diphenyl ester (11), or the corresponding diethyl ester 12, was converted by ammonolysis to 13. The nitrodiurea 13 was next reduced to the amine 14, the hydrochloride of which reacted with ethylene oxide to give the diol 15. Treatment of the latter in dimethylformamide with N-chlorosuccinimide in the presence of triphenylphosphine gave 10 in low yield. The nitrogen mustards 8, 9 and 10 showed significant antitumor activities against P388 lymphocytic leukemia in mice.", "contents": "Synthesis of the antileukemic compound N,N(11)-[5-[bis(2-chloroethyl)amino]-1, 3-phenylene]bisurea. Conversion of 5-nitro-1, 3-benzenedicarboxylic acid (1) to the diamide 2 followed by hypochlorite rearrangement to the idamine 3 and subsequent reaction with acetic anhydride gave the bisacetamide 4. Reduction to the amine 5 followed by treatment with ethylene oxide formed the diol 6. The latter was converted to the bistosylate 7, which undrewent facile displacement with lithium chloride in acetone to give the mustard 8. Removal of the acetyl groups with hydrochloric acid gave 9, which reacted with potassium cyanate to provide the bisurea 10. In an alternative, but less satisfactory synthesis of 10, the compound (5-nitro-1, 3-phenylene) biscarbamic acid diphenyl ester (11), or the corresponding diethyl ester 12, was converted by ammonolysis to 13. The nitrodiurea 13 was next reduced to the amine 14, the hydrochloride of which reacted with ethylene oxide to give the diol 15. Treatment of the latter in dimethylformamide with N-chlorosuccinimide in the presence of triphenylphosphine gave 10 in low yield. The nitrogen mustards 8, 9 and 10 showed significant antitumor activities against P388 lymphocytic leukemia in mice."} {"id": "PMID:1255669", "title": "Structure and antitumor activity relationship of 2-arylidene-4-cyclopentene-1, 3-diones and 2-arylideneindan-1, 3-diones.", "content": "A series of 2-arylidene-4-cyclopentene-1,3-diones and 2-arylideneindan-1,3-diones, as well as mono- and bis(arylidene substituted)cycloalkanones, was synthesized and examined for antitumor activity against ascites sarcoma-180. All the 2-arylidene-4-cyclopentene-1,3-diones and one arylideneindan-1,3-dione (where the arylidene group was either a hydroxybenzylidene or substituted hydroxybenzylidene) exhibited a high degree of activity. Among both types of 1,3-diones and 3-methoxy-4-hydroxybenzylidene derivatives were found to possess the greatest potency, while all the mono- and bis(arylidene)cycloalkanones were found to be inactive.", "contents": "Structure and antitumor activity relationship of 2-arylidene-4-cyclopentene-1, 3-diones and 2-arylideneindan-1, 3-diones. A series of 2-arylidene-4-cyclopentene-1,3-diones and 2-arylideneindan-1,3-diones, as well as mono- and bis(arylidene substituted)cycloalkanones, was synthesized and examined for antitumor activity against ascites sarcoma-180. All the 2-arylidene-4-cyclopentene-1,3-diones and one arylideneindan-1,3-dione (where the arylidene group was either a hydroxybenzylidene or substituted hydroxybenzylidene) exhibited a high degree of activity. Among both types of 1,3-diones and 3-methoxy-4-hydroxybenzylidene derivatives were found to possess the greatest potency, while all the mono- and bis(arylidene)cycloalkanones were found to be inactive."} {"id": "PMID:1255670", "title": "Synthesis and central nervous system depressant activity of some bicyclic amides.", "content": "A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital.", "contents": "Synthesis and central nervous system depressant activity of some bicyclic amides. A series of aryl bicyclic analogs of succinimide and glutarimide was prepared and evaluated for CNS depressant activity. The 8a-aryl-3,4,6,7,8,8a-hexahydro-2H-pyrrolo[2,1-beta][1,3]oxazin-6-ones possessed the best overall spectrum of activity relative to the standard agents glutethimide and phenobarbital."} {"id": "PMID:1255671", "title": "Potentiation of the estrogenic activity of stilbestrol by spiro (cyclohexane-1,2'-indan)-1',4-dione.", "content": "During the investigation of a series of spiro compounds having approximately similar molecular dimensions to naturally occurring estrogens, the novel compound spiro(cyclohexane-1,2'-indan)-1',4-dione was prepared. The pretreatment of mice with this estrogenically inactive compound was found to potentiate the estrogenic activity of stilbestrol.", "contents": "Potentiation of the estrogenic activity of stilbestrol by spiro (cyclohexane-1,2'-indan)-1',4-dione. During the investigation of a series of spiro compounds having approximately similar molecular dimensions to naturally occurring estrogens, the novel compound spiro(cyclohexane-1,2'-indan)-1',4-dione was prepared. The pretreatment of mice with this estrogenically inactive compound was found to potentiate the estrogenic activity of stilbestrol."} {"id": "PMID:1255672", "title": "A senior-year experience similar to an internship.", "content": "A senior year experience similar to an internship was initiated in community hospitals. It is designed to shorten the overall length of training and to restore a broad-based clinical experience to the period of \"intermediate patient care responsibility\" in the training of new physicians. The program provides students with an opportunity to observe and practice in a primary care setting and expands the clinical resources of the medical school. Analysis of the performance of students in the class of 1974 indicates that they perform on a level comparable with first-year house officers. This program provides a general clinical experience for those students who have not yet decided on future training plans or who are going into primary care fields.", "contents": "A senior-year experience similar to an internship. A senior year experience similar to an internship was initiated in community hospitals. It is designed to shorten the overall length of training and to restore a broad-based clinical experience to the period of \"intermediate patient care responsibility\" in the training of new physicians. The program provides students with an opportunity to observe and practice in a primary care setting and expands the clinical resources of the medical school. Analysis of the performance of students in the class of 1974 indicates that they perform on a level comparable with first-year house officers. This program provides a general clinical experience for those students who have not yet decided on future training plans or who are going into primary care fields."} {"id": "PMID:1255673", "title": "A follow-up evaluation of a summer health career program for minority students.", "content": "In an effort to attract minority students to health careers, a special summer education health career experience was developed. A matched comparison group design was utilized to determine the value of this program. Data were collected on both the participants and a matched comparison group three months before and six months after the program. Differences on most of the measures were not significant; however, there was a significant difference on stability of first career choice, indicating that a special summer program can and does have an effect on the participants. The study makes it clear that program effects cannot be assumed unless a follow-up evaluation is undertaken.", "contents": "A follow-up evaluation of a summer health career program for minority students. In an effort to attract minority students to health careers, a special summer education health career experience was developed. A matched comparison group design was utilized to determine the value of this program. Data were collected on both the participants and a matched comparison group three months before and six months after the program. Differences on most of the measures were not significant; however, there was a significant difference on stability of first career choice, indicating that a special summer program can and does have an effect on the participants. The study makes it clear that program effects cannot be assumed unless a follow-up evaluation is undertaken."} {"id": "PMID:1255674", "title": "Relationships between clinical competence ratings and examination performance.", "content": "Relationships between faculty ratings and performance on components of the National Board of Medical Examiners Certifying Examination for Primary Care Physician's Assistants were investigated. A factor analysis of the clinical competence rating form yielded three discrete factors. Results of tests of simple relationships between each rating factor and examination component indicated that four of the six examination components correlated significantly though modestly with at least one of the rating scale factors. The results of multiple regression analyses indicated complex relationships between each of two examination components and the set of rating factors. One implication is that faculty members are able to make discrete judgments about students on more than one dimension.", "contents": "Relationships between clinical competence ratings and examination performance. Relationships between faculty ratings and performance on components of the National Board of Medical Examiners Certifying Examination for Primary Care Physician's Assistants were investigated. A factor analysis of the clinical competence rating form yielded three discrete factors. Results of tests of simple relationships between each rating factor and examination component indicated that four of the six examination components correlated significantly though modestly with at least one of the rating scale factors. The results of multiple regression analyses indicated complex relationships between each of two examination components and the set of rating factors. One implication is that faculty members are able to make discrete judgments about students on more than one dimension."} {"id": "PMID:1255686", "title": "A report on graduates of the Boston University six-year combined liberal-arts--medical program.", "content": "Graduates of a six-year combined Liberal-Arts-Medicine Program and their medical school classmates (traditional \"eight-year\" students) are compared as to their medical school performance and their professional postgraduate activities. On standardized examinations (Medical College Admission Test and examinations of the National Board of Medical Examiners) the six-year group was somewhat better than the eight-year group. In other aspects, such as class ranking, honors at graduation, and medicine clerkship grades, the six- and eight-year groups were similar. The two groups were remarkably similar in their postgraduate professional career choices and in achieving board certification. The data for the first three classes indicate that qualified high school students can succeed academically in an accelerated collegiate-degree program, do well in medical school, achieve postgraduate certification, and begin the practice of medicine at a younger age.", "contents": "A report on graduates of the Boston University six-year combined liberal-arts--medical program. Graduates of a six-year combined Liberal-Arts-Medicine Program and their medical school classmates (traditional \"eight-year\" students) are compared as to their medical school performance and their professional postgraduate activities. On standardized examinations (Medical College Admission Test and examinations of the National Board of Medical Examiners) the six-year group was somewhat better than the eight-year group. In other aspects, such as class ranking, honors at graduation, and medicine clerkship grades, the six- and eight-year groups were similar. The two groups were remarkably similar in their postgraduate professional career choices and in achieving board certification. The data for the first three classes indicate that qualified high school students can succeed academically in an accelerated collegiate-degree program, do well in medical school, achieve postgraduate certification, and begin the practice of medicine at a younger age."} {"id": "PMID:1255687", "title": "The University of Michigan integrated premedical-medical program.", "content": "The University of Michigan Medical School and the College of Literature Science and the Arts are now conducting a six-year program for recent high school graduates which integrates a liberal education and the work necessary for the M. D. degree. There is a single admission point in the spring for seniors in high school. Personal characteristics are heavily emphasized in the admissions process. A number of innovative course sequences have been developed for the program. A variety of evaluation studies are being conducted and will be available as they are completed.", "contents": "The University of Michigan integrated premedical-medical program. The University of Michigan Medical School and the College of Literature Science and the Arts are now conducting a six-year program for recent high school graduates which integrates a liberal education and the work necessary for the M. D. degree. There is a single admission point in the spring for seniors in high school. Personal characteristics are heavily emphasized in the admissions process. A number of innovative course sequences have been developed for the program. A variety of evaluation studies are being conducted and will be available as they are completed."} {"id": "PMID:1255688", "title": "The Lehigh--Medical College of Pennsylvania six-year B.A.-M.D. program.", "content": "Lehigh University and the Medical College of Pennsylvania have developed a program in which selected high school students are admitted directly to medical school. The students spend two years at the university completing the premedical basic sciences and the required humanities and social sciences for the bachelor's degree. Students may choose to extend the two-year university phase to three or four years. Science credit is given by the university for medical school courses, and the student graduates with a B.A. degree after four years and an M.D. degree after six years.", "contents": "The Lehigh--Medical College of Pennsylvania six-year B.A.-M.D. program. Lehigh University and the Medical College of Pennsylvania have developed a program in which selected high school students are admitted directly to medical school. The students spend two years at the university completing the premedical basic sciences and the required humanities and social sciences for the bachelor's degree. Students may choose to extend the two-year university phase to three or four years. Science credit is given by the university for medical school courses, and the student graduates with a B.A. degree after four years and an M.D. degree after six years."} {"id": "PMID:1255689", "title": "Causes of physician migration: responses of Iranian physicians in the United States.", "content": "Each of the 2,270 Iranian physicians listed by the American Medical Association as residing in the United States in 1973 was sent a questionnaire in which he was asked whether or not he intended to return to Iran, his reasons for not returning if he did not intend to return and other questions concerning his history and present status. A total 760 questionnaires were returned. The results indicated that age, level of training, martial status, and previous practice in Iran were all related to intention to return, although whether or not the physician had returned to Iran on a visit was not an important factor. The most frequently cited reasons for not returning were professional reasons, particularly lack of medical facilities and equipment in Iran.", "contents": "Causes of physician migration: responses of Iranian physicians in the United States. Each of the 2,270 Iranian physicians listed by the American Medical Association as residing in the United States in 1973 was sent a questionnaire in which he was asked whether or not he intended to return to Iran, his reasons for not returning if he did not intend to return and other questions concerning his history and present status. A total 760 questionnaires were returned. The results indicated that age, level of training, martial status, and previous practice in Iran were all related to intention to return, although whether or not the physician had returned to Iran on a visit was not an important factor. The most frequently cited reasons for not returning were professional reasons, particularly lack of medical facilities and equipment in Iran."} {"id": "PMID:1255690", "title": "Evolution of a Family Nurse Practitioner Program to improve primary care distribution.", "content": "The Family Nurse Practitioner Program of the Univeristy of California, Davis, has effectively improved the distribution of primary health care manpower in medically underserved areas. This has been accomplished by selecting students, preceptors, and faculty from areas of need; decentralizing the clinical and didactic training sites; developing a competency-based, portable curriculum; and coordinating it all with a circuit-riding, institutionally based faculty.", "contents": "Evolution of a Family Nurse Practitioner Program to improve primary care distribution. The Family Nurse Practitioner Program of the Univeristy of California, Davis, has effectively improved the distribution of primary health care manpower in medically underserved areas. This has been accomplished by selecting students, preceptors, and faculty from areas of need; decentralizing the clinical and didactic training sites; developing a competency-based, portable curriculum; and coordinating it all with a circuit-riding, institutionally based faculty."} {"id": "PMID:1255703", "title": "A comparison of the ability of normal liver, a premalignant liver, a solid hepatoma and the Zajdela ascitic hepatoma, to take up amino acids in vitro.", "content": "The net total uptake of several amino acids at low (0.8-3.1 mumoles/liter) as well as high (800-1200 mumoles/liter) extracellular concentrations, by normal rat liver, a premalignant liver, a solid hepatoma, and the Zajdela ascitic hepatoma cells, has been compared under conditions in which protein synthesis continues. At low amino acid concentrations, the initial (3 min) total uptake of the various amino acids in the Zajdela cells, was 3-10 (average 7) times more, and the intracellular concentration of the labeled amino acids taken up 14-45 (average 31) times more, than in normal liver. At the high amino acid concentrations, the total uptake in the Zajdela cells, at 60-120 min was 2-5 (average 3.5) times more, and the intracellular concentration of the amino acids taken up 8-18 (average 13) times more, than in normal liver; the corresponding values for the premalignant liver and the solid hepatoma were in between those for normal liver and the Zajdela cells. Further, the rate of the total uptake of amino acids, their intracellular concentration, the proportion of the amino acid taken up utilized for protein synthesis, the rate of incorporation of the amino acid taken up into protein, and the cellular growth rate, seemed to be correlated in the four cell/tissue preparations studied. In most cases, the rate of the net uptake fell drastically with time, the uptake virtually stopping after 90-180 min, probably due to lack of serum in the incubation medium.", "contents": "A comparison of the ability of normal liver, a premalignant liver, a solid hepatoma and the Zajdela ascitic hepatoma, to take up amino acids in vitro. The net total uptake of several amino acids at low (0.8-3.1 mumoles/liter) as well as high (800-1200 mumoles/liter) extracellular concentrations, by normal rat liver, a premalignant liver, a solid hepatoma, and the Zajdela ascitic hepatoma cells, has been compared under conditions in which protein synthesis continues. At low amino acid concentrations, the initial (3 min) total uptake of the various amino acids in the Zajdela cells, was 3-10 (average 7) times more, and the intracellular concentration of the labeled amino acids taken up 14-45 (average 31) times more, than in normal liver. At the high amino acid concentrations, the total uptake in the Zajdela cells, at 60-120 min was 2-5 (average 3.5) times more, and the intracellular concentration of the amino acids taken up 8-18 (average 13) times more, than in normal liver; the corresponding values for the premalignant liver and the solid hepatoma were in between those for normal liver and the Zajdela cells. Further, the rate of the total uptake of amino acids, their intracellular concentration, the proportion of the amino acid taken up utilized for protein synthesis, the rate of incorporation of the amino acid taken up into protein, and the cellular growth rate, seemed to be correlated in the four cell/tissue preparations studied. In most cases, the rate of the net uptake fell drastically with time, the uptake virtually stopping after 90-180 min, probably due to lack of serum in the incubation medium."} {"id": "PMID:1255704", "title": "Amide transport channels across toad urinary bladder.", "content": "Urea and other small amides cross the toad urinary bladder by a vasopressinsensitive pathway which is independent of osmotic water flow. Amide transport has characteristics of facilitated transport: saturation, mutual inhibition between amides, and selective depression by agents such as phloretin. The present studies were designed to distinguish among several types of transport including (1) movement through a fixed selective membrane channel and (2) movement via a mobile carrier. The former would be characterized by co-transport (acceleration of labeled amide flow in the direction of net flow of unlabeled amide), the latter by counter-transport (acceleration of labeled amide flow in the opposite direction). Mucosal to serosal (M leads to S) and serosal to mucosal (S leads to M) permeabilities of labeled amides were determined in paired bladders. Unlabeled methylurea, a particularly potent inhibitor of amide movement, was added to either the M or S bath, while osmotic water flow was eliminated by addition of ethylene glycol and ethanol could not be demonstrated. Methylurea did not alter water permeability or transmembrane electrical resistance. The demonstration of co-transport is consistent with the presence of ADH-sensitive amide-selective channels rather than a mobile carrier.", "contents": "Amide transport channels across toad urinary bladder. Urea and other small amides cross the toad urinary bladder by a vasopressinsensitive pathway which is independent of osmotic water flow. Amide transport has characteristics of facilitated transport: saturation, mutual inhibition between amides, and selective depression by agents such as phloretin. The present studies were designed to distinguish among several types of transport including (1) movement through a fixed selective membrane channel and (2) movement via a mobile carrier. The former would be characterized by co-transport (acceleration of labeled amide flow in the direction of net flow of unlabeled amide), the latter by counter-transport (acceleration of labeled amide flow in the opposite direction). Mucosal to serosal (M leads to S) and serosal to mucosal (S leads to M) permeabilities of labeled amides were determined in paired bladders. Unlabeled methylurea, a particularly potent inhibitor of amide movement, was added to either the M or S bath, while osmotic water flow was eliminated by addition of ethylene glycol and ethanol could not be demonstrated. Methylurea did not alter water permeability or transmembrane electrical resistance. The demonstration of co-transport is consistent with the presence of ADH-sensitive amide-selective channels rather than a mobile carrier."} {"id": "PMID:1255728", "title": "Budding by oozooids in the polystyelid ascidian Metandrocarpa tayori Huntsman.", "content": "Larvae of the stolidobranch ascidian Metandrocarpa taylori molt a thin sheath upon settling, then metamorphose and radiate a larval complement of vascular ampullae upon the substrate. These ampullae thereafter regress, \"rest\" in a reduced condition for several weeks, and then regrow into the oozooid's definitive array of vascular ampullae in accompaniment to the development of the oozooidal vascular nest of test-vessels. Pallial buds emerge some four months after the larva settles; the oozooid has by then grown to a length of at least 2 mm and its vascular nest is surrounded by at least 16 vascular ampullae. Oozooids bud one to five buds (mean, 2.6) in a rather short period of blastogenic vigor, then persist in the colony. Late buds are frequently aborted. Buds appear anywhere around the basal margin of the oozooid, but more often on the left than the right and more often posteriorly than anteriorly. As other studies have observed with blastozooids, this study notes an integration of budding and the disposition of the elements of the test-vessel system of oozooids. Buds emerge oriented tangentially to the parental basal margin at the bud-site, then often rotate to point their anterior ends away from the parent. No larvae metamorphosed into oozooids with situs inversus viscerum, but in this study two oozooids extruded blastozooids showing this anomaly; these blastozooids budded \"reversed\" zooids in turn, so that entire clonal lines showed the anomaly.", "contents": "Budding by oozooids in the polystyelid ascidian Metandrocarpa tayori Huntsman. Larvae of the stolidobranch ascidian Metandrocarpa taylori molt a thin sheath upon settling, then metamorphose and radiate a larval complement of vascular ampullae upon the substrate. These ampullae thereafter regress, \"rest\" in a reduced condition for several weeks, and then regrow into the oozooid's definitive array of vascular ampullae in accompaniment to the development of the oozooidal vascular nest of test-vessels. Pallial buds emerge some four months after the larva settles; the oozooid has by then grown to a length of at least 2 mm and its vascular nest is surrounded by at least 16 vascular ampullae. Oozooids bud one to five buds (mean, 2.6) in a rather short period of blastogenic vigor, then persist in the colony. Late buds are frequently aborted. Buds appear anywhere around the basal margin of the oozooid, but more often on the left than the right and more often posteriorly than anteriorly. As other studies have observed with blastozooids, this study notes an integration of budding and the disposition of the elements of the test-vessel system of oozooids. Buds emerge oriented tangentially to the parental basal margin at the bud-site, then often rotate to point their anterior ends away from the parent. No larvae metamorphosed into oozooids with situs inversus viscerum, but in this study two oozooids extruded blastozooids showing this anomaly; these blastozooids budded \"reversed\" zooids in turn, so that entire clonal lines showed the anomaly."} {"id": "PMID:1255729", "title": "Cell division and tissue repair following localized damage to the mammalian lung.", "content": "Small local wounds on the surface of the mouse lung, produced by cauterization, healed by a typical reparative process involving cell migration and increased cell division in alveolar and bronchial tissues. The local cell division response closely resembled the compensatory cell division response in the same organ which follows unilateral pneumonectomy or unilateral collapse of the lung: initially there was an increase in the rate of DNA synthesis followed by an increased rate of entry into mitosis, both of these functions returning to normal levels within a few days. It is therefore suggested that both types of response are governed by a single regulatory mechanism. The results do not support the view that the rate of cell division is regulated by systemically-circulating mitotic control factors and it is proposed that changes in the cell division rate, both in the reparative and in the compensatory types of response, are determined by local alterations in the concentration of regulatory metabolites. The magnitude of the cell division response was much greater in bronchial than in alveolar tissue, a result which is consistent with the view that new alveolar tissue may be produced by the proliferation and diffentiation of bronchial cells.", "contents": "Cell division and tissue repair following localized damage to the mammalian lung. Small local wounds on the surface of the mouse lung, produced by cauterization, healed by a typical reparative process involving cell migration and increased cell division in alveolar and bronchial tissues. The local cell division response closely resembled the compensatory cell division response in the same organ which follows unilateral pneumonectomy or unilateral collapse of the lung: initially there was an increase in the rate of DNA synthesis followed by an increased rate of entry into mitosis, both of these functions returning to normal levels within a few days. It is therefore suggested that both types of response are governed by a single regulatory mechanism. The results do not support the view that the rate of cell division is regulated by systemically-circulating mitotic control factors and it is proposed that changes in the cell division rate, both in the reparative and in the compensatory types of response, are determined by local alterations in the concentration of regulatory metabolites. The magnitude of the cell division response was much greater in bronchial than in alveolar tissue, a result which is consistent with the view that new alveolar tissue may be produced by the proliferation and diffentiation of bronchial cells."} {"id": "PMID:1255730", "title": "The functional anatomy of the hindlimb of some African Viverridae (Carnivora).", "content": "The functional anatomy of the hindlimb of 12 species of viverrids was studied with relation to locomotion. The animals were allocated to primary locomotor categories on the basis of their anatomy and locomotion. The climbing, arboreal walking category (Nandinia binotata) is characterized by a small sacroiliac articulation, the iliopsoas inserts onto a medially located lesser trochanter and the femoral condyles are not posteriorly placed. The hindfoot is plantigrade and its structure permits considerable movement. The pads are soft and the claws retractile. Representatives of the arboreal and terrestrial walking and jumping category (Genetta genetta, G. servalina, G. tigrina) have a plantigrade forefoot and digitigrade hindfoot. The lesser trochanter is more posteriorly placed than in the climbing category. A previously undescribed muscle, the caudofemoralis profundus extends from several anterior caudal vertebrae to the femur. The tibio-astragular joint restricts supination of the foot. There is little mediolateral movement in the digitidgrade foot. The claws are retractile. In the general terrestrial walking and scrambling group (Helogale parvula, Mungos mungo, Atilax paludinosus, Bdeogale crassicauda, Herpestes ichneumon, H. sanguineus) the animals have essentially similar hindlimbs except for size differences and modifications to the feet. Helogale and Mungos have large medial epicondyles on the humerus and large terminal phalanges. Bdeogale has a vestigial first metatarsal, while Atilax can splay its digits. In all species the distal phalanges are non-retractile. The trotting category (Civettictis civetta, Ichneumia albicauda) is characterized by longer epipodials and metapodials and a more proximal position of muscle bellies. Most of the adaptations minimize rotation, adduction and abduction of the leg and supination of the foot. The metatarsals are closely adjoined and the distal phalanx is stout and non-retractile. There appear to be two levels of locomotory adaptation. Major adaptations affect the whole appendicular skeleton and are used to assign animals to primary locomotor categories. Minor adaptations occur mainly in the foot and indicate the more specific habits of the animal.", "contents": "The functional anatomy of the hindlimb of some African Viverridae (Carnivora). The functional anatomy of the hindlimb of 12 species of viverrids was studied with relation to locomotion. The animals were allocated to primary locomotor categories on the basis of their anatomy and locomotion. The climbing, arboreal walking category (Nandinia binotata) is characterized by a small sacroiliac articulation, the iliopsoas inserts onto a medially located lesser trochanter and the femoral condyles are not posteriorly placed. The hindfoot is plantigrade and its structure permits considerable movement. The pads are soft and the claws retractile. Representatives of the arboreal and terrestrial walking and jumping category (Genetta genetta, G. servalina, G. tigrina) have a plantigrade forefoot and digitigrade hindfoot. The lesser trochanter is more posteriorly placed than in the climbing category. A previously undescribed muscle, the caudofemoralis profundus extends from several anterior caudal vertebrae to the femur. The tibio-astragular joint restricts supination of the foot. There is little mediolateral movement in the digitidgrade foot. The claws are retractile. In the general terrestrial walking and scrambling group (Helogale parvula, Mungos mungo, Atilax paludinosus, Bdeogale crassicauda, Herpestes ichneumon, H. sanguineus) the animals have essentially similar hindlimbs except for size differences and modifications to the feet. Helogale and Mungos have large medial epicondyles on the humerus and large terminal phalanges. Bdeogale has a vestigial first metatarsal, while Atilax can splay its digits. In all species the distal phalanges are non-retractile. The trotting category (Civettictis civetta, Ichneumia albicauda) is characterized by longer epipodials and metapodials and a more proximal position of muscle bellies. Most of the adaptations minimize rotation, adduction and abduction of the leg and supination of the foot. The metatarsals are closely adjoined and the distal phalanx is stout and non-retractile. There appear to be two levels of locomotory adaptation. Major adaptations affect the whole appendicular skeleton and are used to assign animals to primary locomotor categories. Minor adaptations occur mainly in the foot and indicate the more specific habits of the animal."} {"id": "PMID:1255731", "title": "Tongue evolution in the lungless salamanders, family plethodontidae. I. Introduction, theory and a general model of dynamics.", "content": "Plethodontid salamanders capture prey by projecting the tongue from the mouth. An analysis of theoretical mechanics of the hyobranchial skeleton is used to formulate a working hypothesis of tongue movements. Predictions that the skeletal elements of the tongue are included in the projectile and that the hyobranchial skeleton is folded during projection are central to the analysis. When decapitated in a particular way, salamanders project the tongue, and it is not retracted. When these heads are fixed and sectioned, examination confirms the predications. In turn, these observations are used to refine the working hypothesis and to generate a general model of tongue dynamics for plethodontids. Muscles performing the major roles of projection (subarcualis rectus I) and retraction (rectus cervicis profundus) are identified. The skeleton is folded passively along a morphological track having the form of a tractrix. Predictions concerning the shape of the track and the exact configuration of the folded skeleton are confirmed by study of sectioned material. The skeleton unfolds along the track during retraction and is spread into the resting state. The model developed herein will be used as a basis for predictions concerning selection patterns in the family and for analytical purposes in comparative and evolutionary studies.", "contents": "Tongue evolution in the lungless salamanders, family plethodontidae. I. Introduction, theory and a general model of dynamics. Plethodontid salamanders capture prey by projecting the tongue from the mouth. An analysis of theoretical mechanics of the hyobranchial skeleton is used to formulate a working hypothesis of tongue movements. Predictions that the skeletal elements of the tongue are included in the projectile and that the hyobranchial skeleton is folded during projection are central to the analysis. When decapitated in a particular way, salamanders project the tongue, and it is not retracted. When these heads are fixed and sectioned, examination confirms the predications. In turn, these observations are used to refine the working hypothesis and to generate a general model of tongue dynamics for plethodontids. Muscles performing the major roles of projection (subarcualis rectus I) and retraction (rectus cervicis profundus) are identified. The skeleton is folded passively along a morphological track having the form of a tractrix. Predictions concerning the shape of the track and the exact configuration of the folded skeleton are confirmed by study of sectioned material. The skeleton unfolds along the track during retraction and is spread into the resting state. The model developed herein will be used as a basis for predictions concerning selection patterns in the family and for analytical purposes in comparative and evolutionary studies."} {"id": "PMID:1255732", "title": "The extrinsic blood vessels of the ovary of the sheep.", "content": "The extrinsic ovarian blood vessels were studied in 134 ewes. In view of recent evidence that uterine luteolysis may involve venoarterial transfer of prostaglandin F2alpha in the ovarian pedicle, particular attention was paid to the interrelationships between veins and arteries. The ovarian artery and utero-ovarian vein are large vessels of conventional structure and lie in close apposition. Their walls are slightly thinner on their apposing sides. The ovarian branches of the ovarian artery are very tortuous, and closely intertwined with the plexiform ovarian branches of the utero-ovarian vein. An extensive plexus of small veins surrounds the ovarian artery and its ovarian branches. Within this plexus are many thin-walled, dilated regions, interspersed with narrow, thick-walled segments. Valves are inconstantly present at sites of entry of branches of the plexus into the major veins. Small numbers of arterio-venous anastomoses are present in the distal part of the ovarian pedicle. Unless blood can flow in a veno-arterial direction through arterio-venous anastomoses or capillary beds, the structural barrier between uterine venous and ovarian arterial blood is substantial.", "contents": "The extrinsic blood vessels of the ovary of the sheep. The extrinsic ovarian blood vessels were studied in 134 ewes. In view of recent evidence that uterine luteolysis may involve venoarterial transfer of prostaglandin F2alpha in the ovarian pedicle, particular attention was paid to the interrelationships between veins and arteries. The ovarian artery and utero-ovarian vein are large vessels of conventional structure and lie in close apposition. Their walls are slightly thinner on their apposing sides. The ovarian branches of the ovarian artery are very tortuous, and closely intertwined with the plexiform ovarian branches of the utero-ovarian vein. An extensive plexus of small veins surrounds the ovarian artery and its ovarian branches. Within this plexus are many thin-walled, dilated regions, interspersed with narrow, thick-walled segments. Valves are inconstantly present at sites of entry of branches of the plexus into the major veins. Small numbers of arterio-venous anastomoses are present in the distal part of the ovarian pedicle. Unless blood can flow in a veno-arterial direction through arterio-venous anastomoses or capillary beds, the structural barrier between uterine venous and ovarian arterial blood is substantial."} {"id": "PMID:1255733", "title": "Feeding adaptations in the hairs and tongues of nectar-feeding bats.", "content": "Scales on the hairs of pollinating bats spread out at an angle to the main hair shaft. In contrast, the hairs of most bats not associated with plants are relatively smooth. Both megachiropteran and microchiropteran flower-feeding bats show this divaricate scale structure which may aid in the collection of a heavy coating of pollen. Some of the pollen is transferred to subsequent flowers, but most is groomed from the fur and ingested as the only reliable nitrogen source for the bat. The tongues of nectar-feeding bats also show structural modifications which allow efficient uptake of the carbohydrate fraction of the diet. Structural specializations of the hiars and tongue are analogous to those seen in other nectar-feeding animals.", "contents": "Feeding adaptations in the hairs and tongues of nectar-feeding bats. Scales on the hairs of pollinating bats spread out at an angle to the main hair shaft. In contrast, the hairs of most bats not associated with plants are relatively smooth. Both megachiropteran and microchiropteran flower-feeding bats show this divaricate scale structure which may aid in the collection of a heavy coating of pollen. Some of the pollen is transferred to subsequent flowers, but most is groomed from the fur and ingested as the only reliable nitrogen source for the bat. The tongues of nectar-feeding bats also show structural modifications which allow efficient uptake of the carbohydrate fraction of the diet. Structural specializations of the hiars and tongue are analogous to those seen in other nectar-feeding animals."} {"id": "PMID:1255734", "title": "Oral food processing in two herbivorous lizards, Iguana iguana (Iguanidae) and Uromastix aegyptius (Agamidae).", "content": "The anatomy and function of the feeding apparatus in Iguana iguana and Uromastix aegyptius were studied by dissection, cinematic and cineradiographic techniques. The feeding behavior of these species differs from that of insectivorous lizards in the cropping action involves movement of both the upper jaw around the atlantooccipital joint and the lower jaw around the mandibular joint; and in Uromastix only, streptostylic movement of the quadrate. Often movements of the whole head play a supplementary role in the cropping action. In both species the feeding apparatus has been modified to facilitate cropping. In Iguana the pleurodont dentition is multicusped and laterally compressed. Each tooth forms a shearing blade whose function does not require contact with other teeth. In Uromastix the dentition is acrodont and the cheek teeth are massive and lack cusps. Occlusion is necessary for shearing plant material. The skull system of Uromastix also has a number of modified structures which allow protraction and retraction of the lower jaw to facilitate cropping while maintaining a gape equivalent to that in Iguana. It is suggested that the differences in the feeding apparatus between Iguana and Uromastix are attributable to differeces in the mode of tooth replacement and implantation.", "contents": "Oral food processing in two herbivorous lizards, Iguana iguana (Iguanidae) and Uromastix aegyptius (Agamidae). The anatomy and function of the feeding apparatus in Iguana iguana and Uromastix aegyptius were studied by dissection, cinematic and cineradiographic techniques. The feeding behavior of these species differs from that of insectivorous lizards in the cropping action involves movement of both the upper jaw around the atlantooccipital joint and the lower jaw around the mandibular joint; and in Uromastix only, streptostylic movement of the quadrate. Often movements of the whole head play a supplementary role in the cropping action. In both species the feeding apparatus has been modified to facilitate cropping. In Iguana the pleurodont dentition is multicusped and laterally compressed. Each tooth forms a shearing blade whose function does not require contact with other teeth. In Uromastix the dentition is acrodont and the cheek teeth are massive and lack cusps. Occlusion is necessary for shearing plant material. The skull system of Uromastix also has a number of modified structures which allow protraction and retraction of the lower jaw to facilitate cropping while maintaining a gape equivalent to that in Iguana. It is suggested that the differences in the feeding apparatus between Iguana and Uromastix are attributable to differeces in the mode of tooth replacement and implantation."} {"id": "PMID:1255743", "title": "Synthesis of immunoglobulin and Marek's disease virus antibody in susceptible and relatively resistant chickens.", "content": "The levels of IgM, IgY, and IgA and the development of specific antibody to Marek's disease virus (MDV) and sheep red blood cells (SRBC) in young chickens susceptible and resistant to Marek's disease were compared after exposure to MDV. No significant difference was noted in the immunoglobulin levels. However, the antibody response to MDV and SRBC occurred more rapidly in susceptible birds. The initial titer of antibody to these antigens was higher. These differences in response, however, were transient. At 3 weeks post exposure, the levels of IgM antibodies to MDV and antibodies to SRBC were similar in the two lines of chickens. At 6 weeks, the levels of IgY antibodies to MDV and antibodies detected by the agar gel precipitation test were similar.", "contents": "Synthesis of immunoglobulin and Marek's disease virus antibody in susceptible and relatively resistant chickens. The levels of IgM, IgY, and IgA and the development of specific antibody to Marek's disease virus (MDV) and sheep red blood cells (SRBC) in young chickens susceptible and resistant to Marek's disease were compared after exposure to MDV. No significant difference was noted in the immunoglobulin levels. However, the antibody response to MDV and SRBC occurred more rapidly in susceptible birds. The initial titer of antibody to these antigens was higher. These differences in response, however, were transient. At 3 weeks post exposure, the levels of IgM antibodies to MDV and antibodies to SRBC were similar in the two lines of chickens. At 6 weeks, the levels of IgY antibodies to MDV and antibodies detected by the agar gel precipitation test were similar."} {"id": "PMID:1255744", "title": "Transmission of BCG-associated tumor resistance from maternal to newborn guinea pigs.", "content": "Resistance to line-10 hepatocarcinoma was studied in the newborn offspring of inbred strain-2 Sewall Wright guinea pigs that had recovered from this tumor after prior administration of subcellular components of Mycobacterium bovis strain BCG. These mothers gave birth to 15 offspring, 53% of which resisted repeated challenges with this tumor. Offspring of mothers who had been given only BCG components were similarly tested. Complete protection was observed in 23.5% of 17 babies and attenuation of disease in many others. All control offspring from normal, untreated mothers succumbed to this tumor. Resistance was associated with delayed cutaneous hypersensitivity reactions to tumor and mycobacterial antigens.", "contents": "Transmission of BCG-associated tumor resistance from maternal to newborn guinea pigs. Resistance to line-10 hepatocarcinoma was studied in the newborn offspring of inbred strain-2 Sewall Wright guinea pigs that had recovered from this tumor after prior administration of subcellular components of Mycobacterium bovis strain BCG. These mothers gave birth to 15 offspring, 53% of which resisted repeated challenges with this tumor. Offspring of mothers who had been given only BCG components were similarly tested. Complete protection was observed in 23.5% of 17 babies and attenuation of disease in many others. All control offspring from normal, untreated mothers succumbed to this tumor. Resistance was associated with delayed cutaneous hypersensitivity reactions to tumor and mycobacterial antigens."} {"id": "PMID:1255745", "title": "Antigenic cross-reactivity between adenocarcinoma of the breast and fibrocystic disease of the breast.", "content": "Peripheral lymphocytes obtained from 12 of 13 patients who had fibrocystic disease (FCD) of the breast were specifically cytotoxic to breast adenocarcinoma cells, as measured in vitro by the microcytotoxicity test. Sera from 6 women with active FCD or metastatic breast cancer could specifically block the cytotoxicity of lymphocytes from either population of patients against cancer cells. This implied extensive antigenic cross-reactivity between benign and malignant hyperplastic disease of the breast. Sera from 4 individuals clinically free of FCD or breast fibroadenoma (FAD) neutralized the blocking activity in the sera of patients with metastatic breast cancer. Patients \"cured\" of FCD or FAD represented a pool of potential plasma donors for immunotherapy of recurrent breast cancer.", "contents": "Antigenic cross-reactivity between adenocarcinoma of the breast and fibrocystic disease of the breast. Peripheral lymphocytes obtained from 12 of 13 patients who had fibrocystic disease (FCD) of the breast were specifically cytotoxic to breast adenocarcinoma cells, as measured in vitro by the microcytotoxicity test. Sera from 6 women with active FCD or metastatic breast cancer could specifically block the cytotoxicity of lymphocytes from either population of patients against cancer cells. This implied extensive antigenic cross-reactivity between benign and malignant hyperplastic disease of the breast. Sera from 4 individuals clinically free of FCD or breast fibroadenoma (FAD) neutralized the blocking activity in the sera of patients with metastatic breast cancer. Patients \"cured\" of FCD or FAD represented a pool of potential plasma donors for immunotherapy of recurrent breast cancer."} {"id": "PMID:1255746", "title": "Trisomy of the long arm of chromosome No. 1 in human leukemia.", "content": "We encountered a karyotypic abnormality, i.e. a trisomy of part of or the whole long arm of chromosome No. 1, in 4 patients with leukemia; 3 with acute myeloblastic, leukemia (AML) and 1 with chronic myelocytic leukemia (CML) in the blastic phase. Q- and G-banding techniques revealed that in two patients with AML and in the one with CML, this karyotypic abnormality was not an initial one and was apparently associated with clinical progression of the disease. This chromosome change is a common karyotypic abnormality in blood disorders, especially in AML, and possibly bears a relationship to selective growth advantages of the leukemia cells.", "contents": "Trisomy of the long arm of chromosome No. 1 in human leukemia. We encountered a karyotypic abnormality, i.e. a trisomy of part of or the whole long arm of chromosome No. 1, in 4 patients with leukemia; 3 with acute myeloblastic, leukemia (AML) and 1 with chronic myelocytic leukemia (CML) in the blastic phase. Q- and G-banding techniques revealed that in two patients with AML and in the one with CML, this karyotypic abnormality was not an initial one and was apparently associated with clinical progression of the disease. This chromosome change is a common karyotypic abnormality in blood disorders, especially in AML, and possibly bears a relationship to selective growth advantages of the leukemia cells."} {"id": "PMID:1255747", "title": "Development of fewer tumor colonies in lungs of athymic nude mice after intravenous injection of tumor cells.", "content": "The formation of tumor colonies was compared in the lungs of athymic nude and normal littermate mice after an iv injection of transplantable syngeneic tumor cells. Each of 5 tumors tested formed fewer colonies in the lungs of nude recepients.", "contents": "Development of fewer tumor colonies in lungs of athymic nude mice after intravenous injection of tumor cells. The formation of tumor colonies was compared in the lungs of athymic nude and normal littermate mice after an iv injection of transplantable syngeneic tumor cells. Each of 5 tumors tested formed fewer colonies in the lungs of nude recepients."} {"id": "PMID:1255748", "title": "Factors involved in concanavalin A agglutination of KB and NC37 cells grown in suspension culture.", "content": "NC37 and KB cells grown in suspension culture remained agglutinable at 23 degrees C by concanavalin A (Con A) after sufficient glutaraldehyde fixation to prevent lateral mobility (clustering) of Con A binding sites. In contrast, at 4 degrees C agglutination of the fixed cells was blocked. No significant differences in 3H-Con A binding were observed between unfixed cells and glutaraldehyde-fixed cells at 23 degrees C and unfixed cells at 4 degrees C. Con A bound to fixed cells at 4 degrees C produced agglutination when the cells were washed and then warmed to 23 degrees C. Thus a cold-sensitive factor unrelated to the binding of Con A or the clustering of Con A sites is necessary for agglutination to occur.", "contents": "Factors involved in concanavalin A agglutination of KB and NC37 cells grown in suspension culture. NC37 and KB cells grown in suspension culture remained agglutinable at 23 degrees C by concanavalin A (Con A) after sufficient glutaraldehyde fixation to prevent lateral mobility (clustering) of Con A binding sites. In contrast, at 4 degrees C agglutination of the fixed cells was blocked. No significant differences in 3H-Con A binding were observed between unfixed cells and glutaraldehyde-fixed cells at 23 degrees C and unfixed cells at 4 degrees C. Con A bound to fixed cells at 4 degrees C produced agglutination when the cells were washed and then warmed to 23 degrees C. Thus a cold-sensitive factor unrelated to the binding of Con A or the clustering of Con A sites is necessary for agglutination to occur."} {"id": "PMID:1255750", "title": "Protein and RNA synthesis in pituitary tumors from F344 rats given implants of estrogen.", "content": "The synthesis of total proteins, growth hormone, and prolactin and the incorporation of radioactive precursors into RNA was studied in Pituitaries from normal F344 rats and rats given implants of 15 mg diethylstilbestrol (DES). Prolonged DES treatment (greater than 50 days) induced pituitary tumors in male and female rats. The tumor tissue had a high rate of cell protein synthesis and an unusual capacity to synthesize a single-protein hormone (prolactin). After 17 days of DES treatment, the increase in prolactin synthesis in the hyperplastic pituitaries was not as marked as that in the tumors. At the time of tumor induction and high prolactin synthesis, incorporation of uridine or cytidine into RNA was not stimulated, and orotic acid incorporation in tumors from male rats was decreased. During early estrogen treatment (5 and 17 days), significantly less uridine was incorporated into RNA. These data suggested that the increment in protein and hormone synthesis promoted by DES may be related to a decrease in RNA turnover.", "contents": "Protein and RNA synthesis in pituitary tumors from F344 rats given implants of estrogen. The synthesis of total proteins, growth hormone, and prolactin and the incorporation of radioactive precursors into RNA was studied in Pituitaries from normal F344 rats and rats given implants of 15 mg diethylstilbestrol (DES). Prolonged DES treatment (greater than 50 days) induced pituitary tumors in male and female rats. The tumor tissue had a high rate of cell protein synthesis and an unusual capacity to synthesize a single-protein hormone (prolactin). After 17 days of DES treatment, the increase in prolactin synthesis in the hyperplastic pituitaries was not as marked as that in the tumors. At the time of tumor induction and high prolactin synthesis, incorporation of uridine or cytidine into RNA was not stimulated, and orotic acid incorporation in tumors from male rats was decreased. During early estrogen treatment (5 and 17 days), significantly less uridine was incorporated into RNA. These data suggested that the increment in protein and hormone synthesis promoted by DES may be related to a decrease in RNA turnover."} {"id": "PMID:1255751", "title": "Oncogenic response of rats with x-ray-induced microcephaly to transplacental ethylnitrosourea.", "content": "The relation of congenital malformations to tumor development was examined. Pregnant Sprague-Dawley rats were given 200 rads of X-rays on the 15th or 16th day of gestation and injections of 10 mg ethylnitrosourea (ENU)/kg 1-4 days later, or they were irradiated or injected only. Surviving weanlings that had been irradiated had micrencephaly and other malformations. Offspring exposed to ENU only had no external deformities. By 15 months of age 16.7% of the offspring exposed to X-rays and ENU prenatally had developed neurogenic tumors, whereas 62.2% of those exposed to ENU alone had developed tumors. Those only irradiated had no tumors. Both of the former groups developed oligodendrogliomas, mixed gliomas, ependymomas, and schwannomas, but the first manifestations of tumors occurred later in the group receiving the combined treatment. This delay persisted furing the subsequent period of the study.", "contents": "Oncogenic response of rats with x-ray-induced microcephaly to transplacental ethylnitrosourea. The relation of congenital malformations to tumor development was examined. Pregnant Sprague-Dawley rats were given 200 rads of X-rays on the 15th or 16th day of gestation and injections of 10 mg ethylnitrosourea (ENU)/kg 1-4 days later, or they were irradiated or injected only. Surviving weanlings that had been irradiated had micrencephaly and other malformations. Offspring exposed to ENU only had no external deformities. By 15 months of age 16.7% of the offspring exposed to X-rays and ENU prenatally had developed neurogenic tumors, whereas 62.2% of those exposed to ENU alone had developed tumors. Those only irradiated had no tumors. Both of the former groups developed oligodendrogliomas, mixed gliomas, ependymomas, and schwannomas, but the first manifestations of tumors occurred later in the group receiving the combined treatment. This delay persisted furing the subsequent period of the study."} {"id": "PMID:1255752", "title": "Natural antibodies to human lymphocytes in murine strains.", "content": "Murine strains vary greatly in their content of natural antibodies to human lymphocytes; sera from NZB, B10.BR/TSn, DBA/J, and B10.S mice reacted with more than 90% of the panel of human lymphocytes, yet those from other strains did not react. These levels of natural antibodies to human lymphocytes did not correlate with the H-2 type of mice, but appeared to be a dominant character with incomplete penetrance. Since sera from germfree mice also contained natural antibodies to human lymphocytes, their formation was not influenced substantially by bacteria.", "contents": "Natural antibodies to human lymphocytes in murine strains. Murine strains vary greatly in their content of natural antibodies to human lymphocytes; sera from NZB, B10.BR/TSn, DBA/J, and B10.S mice reacted with more than 90% of the panel of human lymphocytes, yet those from other strains did not react. These levels of natural antibodies to human lymphocytes did not correlate with the H-2 type of mice, but appeared to be a dominant character with incomplete penetrance. Since sera from germfree mice also contained natural antibodies to human lymphocytes, their formation was not influenced substantially by bacteria."} {"id": "PMID:1255753", "title": "Antitumor immunity. II. Viability, tumorigenicity, and immunogenicity of neuraminidase-treated tumor cells: effective immunization of animals with a tumor vaccine.", "content": "A dimethylbenzdithionaphthene (DBDN)-induced fibrosarcoma showed reduced transplantability if previously treated with Vibrio cholerae neuraminidase (VCN). However, the reduced transplantability of VCN-treated tumor cells was not associated with any loss of their viability or tumorigenic capability, but appeared to be due to their increase in immunogenicity. High doses of VCN-treated tumor cells could grow even in normal individuals. Lower doses, which did not induce tumor development in normal individuals, did so if injected into immunosuppressed animals. Although X-irradiation of VCN-treated tumor cells reduced their tumorigenic potential, it did not impair their increased immunogenic properties. Thus a suitable method for the preparation of a \"tumor vaccine\" was provided. The immunization of animals with the vaccine and a working hypothesis regarding its mechanism of action were described.", "contents": "Antitumor immunity. II. Viability, tumorigenicity, and immunogenicity of neuraminidase-treated tumor cells: effective immunization of animals with a tumor vaccine. A dimethylbenzdithionaphthene (DBDN)-induced fibrosarcoma showed reduced transplantability if previously treated with Vibrio cholerae neuraminidase (VCN). However, the reduced transplantability of VCN-treated tumor cells was not associated with any loss of their viability or tumorigenic capability, but appeared to be due to their increase in immunogenicity. High doses of VCN-treated tumor cells could grow even in normal individuals. Lower doses, which did not induce tumor development in normal individuals, did so if injected into immunosuppressed animals. Although X-irradiation of VCN-treated tumor cells reduced their tumorigenic potential, it did not impair their increased immunogenic properties. Thus a suitable method for the preparation of a \"tumor vaccine\" was provided. The immunization of animals with the vaccine and a working hypothesis regarding its mechanism of action were described."} {"id": "PMID:1255754", "title": "Antigenic changes of L5178Y lymphoma after treatment with 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide in vivo.", "content": "Immunologic alteration of the L5178Y lymphoma was obtained in vivo after treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC). A single dose of 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) \"CURED\" MICE CHALLENGED WITH L5178Y cells that had been treated with DIC (L5178Y/DIC) for four transplant generations; BCNU did not cure mice bearing the parent tumor. The L5178Y/DIC, treated in vivo for five transplant generations, id not grow in syngeneic mice. L5178Y/OIC cell growth and incidences of death were similar to those of parent cells when inoculated into heavily immunosuppressed mice. Adoptive transfer of lymphocytes from spleens of mice sensitized to the drug-altered tumor specifically protected immunosuppressed mice bearing the L5178Y/DIC tumor. Little protection was afforded by lymphocytes immune to the parent L5178Y tumor, whereas nonimmune lymphocytes or lymphocytes immune against unrelated tumors were completely ineffective. Anti-L5178Y/DIC lymphocytes did not cure mice challenged with the parent L5178Y tumor. Irradiated (400 R) mice previously sensitized to L5178Y/DIC cells rejected 10(2)-10(7) inocula of L5178Y/DIC cells and died when the parent L5178Y was used for challenge. It was concluded that antigeni( alterations of L5178Y cells occurred in (BALB/ctcr X DBA/2Cr)F1 mice after treatment with DIC in vivo.", "contents": "Antigenic changes of L5178Y lymphoma after treatment with 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide in vivo. Immunologic alteration of the L5178Y lymphoma was obtained in vivo after treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC). A single dose of 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) \"CURED\" MICE CHALLENGED WITH L5178Y cells that had been treated with DIC (L5178Y/DIC) for four transplant generations; BCNU did not cure mice bearing the parent tumor. The L5178Y/DIC, treated in vivo for five transplant generations, id not grow in syngeneic mice. L5178Y/OIC cell growth and incidences of death were similar to those of parent cells when inoculated into heavily immunosuppressed mice. Adoptive transfer of lymphocytes from spleens of mice sensitized to the drug-altered tumor specifically protected immunosuppressed mice bearing the L5178Y/DIC tumor. Little protection was afforded by lymphocytes immune to the parent L5178Y tumor, whereas nonimmune lymphocytes or lymphocytes immune against unrelated tumors were completely ineffective. Anti-L5178Y/DIC lymphocytes did not cure mice challenged with the parent L5178Y tumor. Irradiated (400 R) mice previously sensitized to L5178Y/DIC cells rejected 10(2)-10(7) inocula of L5178Y/DIC cells and died when the parent L5178Y was used for challenge. It was concluded that antigeni( alterations of L5178Y cells occurred in (BALB/ctcr X DBA/2Cr)F1 mice after treatment with DIC in vivo."} {"id": "PMID:1255758", "title": "Ultrastructural studies of surface features of human normal and tumor cells in tissue culture by scanning and transmission electron microscopy.", "content": "Human tumors of a variety of histopathologic types have been established in tissue culture. The surface features of these cell lines were investigated by scanning electron microscopy (SEM) with the use of new techniques for specimen preparation. Tumor cells demonstrated striking degrees of surface activity with numerous microvilli, filopodia, blebs, and ruffles. Intercellular contacts were also prominent in cultures of most solid tumors observed by SEM. At low cell density, normal human fibroblasts exhibited some surface features such as microvilli and blebs, but at higher cell density they lacked extensive surface modifications. By transmission electron microscopy (TEM), the cytoskeleton of normal fibroblasts was shown to be well organized, with parallel orientation of microfilaments, filaments, and microtubules. These structures were also in tumor cells, but they lacked the degree of organization of fibroblasts. Desmosomes were readily demonstrated in normal fibroblasts and carcinoma cells in culture but not in sarcomas, melanomas, or tumors of neural origin. These studies have provided the first correlative SEM and TEM analyses of solid human tumor cells of diverse pathologic types in vitro.", "contents": "Ultrastructural studies of surface features of human normal and tumor cells in tissue culture by scanning and transmission electron microscopy. Human tumors of a variety of histopathologic types have been established in tissue culture. The surface features of these cell lines were investigated by scanning electron microscopy (SEM) with the use of new techniques for specimen preparation. Tumor cells demonstrated striking degrees of surface activity with numerous microvilli, filopodia, blebs, and ruffles. Intercellular contacts were also prominent in cultures of most solid tumors observed by SEM. At low cell density, normal human fibroblasts exhibited some surface features such as microvilli and blebs, but at higher cell density they lacked extensive surface modifications. By transmission electron microscopy (TEM), the cytoskeleton of normal fibroblasts was shown to be well organized, with parallel orientation of microfilaments, filaments, and microtubules. These structures were also in tumor cells, but they lacked the degree of organization of fibroblasts. Desmosomes were readily demonstrated in normal fibroblasts and carcinoma cells in culture but not in sarcomas, melanomas, or tumors of neural origin. These studies have provided the first correlative SEM and TEM analyses of solid human tumor cells of diverse pathologic types in vitro."} {"id": "PMID:1255759", "title": "Stomach cancer in Japan.", "content": "A study of 783 patients with stomach cancer and 1,566 hospital controls in Hiroshima and Miyagi prefectures of Japan showed that farmers, representing mostly the lowest socioeconomic class, had higher risk of developing stomach cancer. The usual inverse gradient in risk by social class was in the urban population of Miyagi, but not Hiroshima, prefecture. The study in Japan did not reproduce the association of stomach cancer with consumption of salted/dried fish and salt-pickled vegetables described for the Hawaiian Japanese. Salted/dried fish and pickled vegetables were more widely used by farmers than by nonfarmers in Japan or by Japanese migrants to Hawaii. The ability to detect associations for these typical Japanese foods in Hawaii stemmed from the fact that these reduced levels of use were more completely expressed by the Hawaiian-Japanese controls than by patients. The lower risk of developing stomach cancer for lettuce and celery users agreed with the Hawaiian-Japanese findings, and the combined results supported conjectures on possible protective food effects. Lettuce, in particular, warranted attention from this viewpoint, since similar findings have been consistently reported.", "contents": "Stomach cancer in Japan. A study of 783 patients with stomach cancer and 1,566 hospital controls in Hiroshima and Miyagi prefectures of Japan showed that farmers, representing mostly the lowest socioeconomic class, had higher risk of developing stomach cancer. The usual inverse gradient in risk by social class was in the urban population of Miyagi, but not Hiroshima, prefecture. The study in Japan did not reproduce the association of stomach cancer with consumption of salted/dried fish and salt-pickled vegetables described for the Hawaiian Japanese. Salted/dried fish and pickled vegetables were more widely used by farmers than by nonfarmers in Japan or by Japanese migrants to Hawaii. The ability to detect associations for these typical Japanese foods in Hawaii stemmed from the fact that these reduced levels of use were more completely expressed by the Hawaiian-Japanese controls than by patients. The lower risk of developing stomach cancer for lettuce and celery users agreed with the Hawaiian-Japanese findings, and the combined results supported conjectures on possible protective food effects. Lettuce, in particular, warranted attention from this viewpoint, since similar findings have been consistently reported."} {"id": "PMID:1255760", "title": "The zinc glycinate marker in human colon carcinoma.", "content": "In an attempt to identify new tumor markers in human colon carcinoma, we produced antisera in rabbits tolerant to normal human tissue antigens and immunized with zinc glycinate-treated extracts of liver metastases from a colon carcinoma. These antisera reacted with carcinoembryonic antigen and with an additional component present in the tumor extracts but not detected in the extracts of normal tissues. The new component, the zinc glycinate marker (ZGM), had an alpha2 mobility on immunoelectrophoresis, was soluble in 1 M perchloric acid, and had a molecular weight of approximately 2X10(6), as indicated by its elution pattern on Sepharose 6-B chromatography. It differed from alpha fetoprotein, nonspecific cross-reacting antigens (NCA, NGP, or CCA III), ferritin-like molecules, and blood group substances A, B, H, Lewis a, and Lewis b. The ZGM was similarly identified in saline or zinc glycinate extracts of 11 of 23 carcinomas of the colon. With routine hematoxylineosin staining, no histologic differences were apparent between tumors bearing the antigen and those without it.", "contents": "The zinc glycinate marker in human colon carcinoma. In an attempt to identify new tumor markers in human colon carcinoma, we produced antisera in rabbits tolerant to normal human tissue antigens and immunized with zinc glycinate-treated extracts of liver metastases from a colon carcinoma. These antisera reacted with carcinoembryonic antigen and with an additional component present in the tumor extracts but not detected in the extracts of normal tissues. The new component, the zinc glycinate marker (ZGM), had an alpha2 mobility on immunoelectrophoresis, was soluble in 1 M perchloric acid, and had a molecular weight of approximately 2X10(6), as indicated by its elution pattern on Sepharose 6-B chromatography. It differed from alpha fetoprotein, nonspecific cross-reacting antigens (NCA, NGP, or CCA III), ferritin-like molecules, and blood group substances A, B, H, Lewis a, and Lewis b. The ZGM was similarly identified in saline or zinc glycinate extracts of 11 of 23 carcinomas of the colon. With routine hematoxylineosin staining, no histologic differences were apparent between tumors bearing the antigen and those without it."} {"id": "PMID:1255761", "title": "Mutagenicity of metronidazole: presence of several active metabolites in human urine.", "content": "Mutagenic activity was found in the urine of 10 patients given therapeutic dosages of metronidazole orally or per vagina. Paper chromatographic separation revealed that mutagenicity in the urine was associated with unmodified metronidazole and at least four of its known urinary metabolites. Activity was also recovered in a region of the chromatogram heretofore not assigned to a metronidazole metabolite.", "contents": "Mutagenicity of metronidazole: presence of several active metabolites in human urine. Mutagenic activity was found in the urine of 10 patients given therapeutic dosages of metronidazole orally or per vagina. Paper chromatographic separation revealed that mutagenicity in the urine was associated with unmodified metronidazole and at least four of its known urinary metabolites. Activity was also recovered in a region of the chromatogram heretofore not assigned to a metronidazole metabolite."} {"id": "PMID:1255762", "title": "Spontaneous tumors in the Dunkin-Hartley guinea pig.", "content": "Seventy-nine spontaneous neoplasms in Dunkin-Hartley guinea pigs were observed over a 9-year period in the Fort Detrick guinea pig colony. Sixty-three of the neoplasms were found during approximately 8,500 necropsies performed on animals under 27 months of age. The remaining 16 tumors were in 34 breeders maintained after 27 months of age on a natural life-span study. Of this group, 10 (29.4%) developed neoplasms by the termination of the study, when the animals were 80 months of age. The skin tumor, trichofolliculoma, of which there were 29, comprised the largest tumor classification.", "contents": "Spontaneous tumors in the Dunkin-Hartley guinea pig. Seventy-nine spontaneous neoplasms in Dunkin-Hartley guinea pigs were observed over a 9-year period in the Fort Detrick guinea pig colony. Sixty-three of the neoplasms were found during approximately 8,500 necropsies performed on animals under 27 months of age. The remaining 16 tumors were in 34 breeders maintained after 27 months of age on a natural life-span study. Of this group, 10 (29.4%) developed neoplasms by the termination of the study, when the animals were 80 months of age. The skin tumor, trichofolliculoma, of which there were 29, comprised the largest tumor classification."} {"id": "PMID:1255763", "title": "Occurrence of hematopoietic neoplasms in Virginia oysters (Crassostrea virginica).", "content": "A neoplastic disease of the hematopoietic system of oysters was found in tray-cultured native and laboratory-bred populations and was associated with mortalities during field monitoring. The disease, characterized by nuclear abnormalities and intensive proliferation of hemocytes, was first observed at the Virginia Institute of Marine Science in 1963. Cases rarely occurred during 14 years (1959-1973 inclusive) of regular sampling and monitoring of thousands of oysters. However, two groups exhibited a high susceptibility to this disease in a program of intensive inbreeding to achieve genetic resistance to oyster pathogens.", "contents": "Occurrence of hematopoietic neoplasms in Virginia oysters (Crassostrea virginica). A neoplastic disease of the hematopoietic system of oysters was found in tray-cultured native and laboratory-bred populations and was associated with mortalities during field monitoring. The disease, characterized by nuclear abnormalities and intensive proliferation of hemocytes, was first observed at the Virginia Institute of Marine Science in 1963. Cases rarely occurred during 14 years (1959-1973 inclusive) of regular sampling and monitoring of thousands of oysters. However, two groups exhibited a high susceptibility to this disease in a program of intensive inbreeding to achieve genetic resistance to oyster pathogens."} {"id": "PMID:1255764", "title": "Antibodies in normal rabbit serum that react with tissue-specific antigens on the plasma membranes of human adenocarcinoma cells.", "content": "Indirect viable cell immunofluorescence studies revealed, on the plasma membrane of cultured adenocarcinoma cells from the human colon and rectum, a tissue-specific antigen that reacted with a component of normal rabbit serum. The use of G200 column chromatography and monospecific antisera prepared against class-specific heavy chains of rabbit immunoglobulin indentified the reactive components in rabbit serum as IgM. Examination of normal and malignant cells from various human tissues by immunofluorescence and adsorption studies showed that rabbit serum reacted only with cells derived from the intestinal epithelium.", "contents": "Antibodies in normal rabbit serum that react with tissue-specific antigens on the plasma membranes of human adenocarcinoma cells. Indirect viable cell immunofluorescence studies revealed, on the plasma membrane of cultured adenocarcinoma cells from the human colon and rectum, a tissue-specific antigen that reacted with a component of normal rabbit serum. The use of G200 column chromatography and monospecific antisera prepared against class-specific heavy chains of rabbit immunoglobulin indentified the reactive components in rabbit serum as IgM. Examination of normal and malignant cells from various human tissues by immunofluorescence and adsorption studies showed that rabbit serum reacted only with cells derived from the intestinal epithelium."} {"id": "PMID:1255765", "title": "Antibody-dependent, cell-mediated cytotoxicity with autochthonous lymphocytes and sera after infection with Moloney sarcoma virus.", "content": "Antibody-dependent, cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was analyzed in terms of the ability of autochthonous antibody to induce or potentiate cytotoxicity by lymphocytes from animals infected with MSV. As previously demonstrated in microcytotoxicity assays, the lymphocytes from regressor animals taken 30 days after virus infection were consistently more cytotoxic than those from tumor-bearing animals 15 days after infection. Antisera from the regressors potentiated the activity of regressor lymphocytes from the same animals. Also, antisera from tumor bearers, 15 days after virus injection, induced cytotoxicity by the animals' autochthonous lymphocytes which, by themselves, were not cytotoxic. In an independent assay for antibody, both groups of sera produced cytotoxicity by control nonimmune lymphocytes. Specificity controls indicated that both antibody and lymphocytes were required for the induction of cytotoxicity against the target cells in vitro. Normal sera placed on the target cells in the same concentrations induced no cytotoxicity by the immune lymphocytes, and immune sera alone placed on the target cells caused no cytotoxicity. The cooperative activity between antibody and lymphocytes may be a factor that accounts for the observed high incidence of spontaneous tumor regression.", "contents": "Antibody-dependent, cell-mediated cytotoxicity with autochthonous lymphocytes and sera after infection with Moloney sarcoma virus. Antibody-dependent, cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was analyzed in terms of the ability of autochthonous antibody to induce or potentiate cytotoxicity by lymphocytes from animals infected with MSV. As previously demonstrated in microcytotoxicity assays, the lymphocytes from regressor animals taken 30 days after virus infection were consistently more cytotoxic than those from tumor-bearing animals 15 days after infection. Antisera from the regressors potentiated the activity of regressor lymphocytes from the same animals. Also, antisera from tumor bearers, 15 days after virus injection, induced cytotoxicity by the animals' autochthonous lymphocytes which, by themselves, were not cytotoxic. In an independent assay for antibody, both groups of sera produced cytotoxicity by control nonimmune lymphocytes. Specificity controls indicated that both antibody and lymphocytes were required for the induction of cytotoxicity against the target cells in vitro. Normal sera placed on the target cells in the same concentrations induced no cytotoxicity by the immune lymphocytes, and immune sera alone placed on the target cells caused no cytotoxicity. The cooperative activity between antibody and lymphocytes may be a factor that accounts for the observed high incidence of spontaneous tumor regression."} {"id": "PMID:1255766", "title": "A new culture model facilitating rapid quantitative testing of mitotic spindle inhibition in mammalian cells.", "content": "A new culture model, which facilitated both mass screening of potential anticancer drugs acting on microtubules and quantitative experiments with known \"antitubulins,\" was found to have the following advantages: use of mammalian cells (either transformed or not), simplicity of the techniques (phase-contrast microscopy or simple microscopy after Giemsa staining), and ease with which it lent itself to quantification. The model was based on the uniform multimicronucleation response induced by antitubulins in MO cells. The specificity (towards antitubulins) of this response was ascertained by the use of many substances, including most of the known antitubulins and a number of nonrelated cytostatic or cytotoxic compounds. The uniformity of the response was established with the use of time-lapse observation of large numbers of cells and quantitative approaches. The results obtained in this model with the standard antitubulins (colchicine, vinblastine, vincristine) showed similar effects. The major difference between colchicine and the Vinca alkaloids was that colchicine was less reversible, which might be an indication of stronger intracellular binding. The Vinca alkaloids acted synergistically with colchicine when threshold subactive doses were combined, although it is known that they bind at a different site on tubulins. A number of substances that have been claimed or were suspected to interfere with microtubules were tested. The results showed that the following substances were indeed active with MO cells: colchicine, vinblastine, vincristine, podophyllotoxin, rotenone, griseofulvin, mercaptoethanol, benomyl, methyl benzimidazol-2-yl carbamate, and R 17934. Compounds that were inactive on these mammalian cells in culture included isopropyl carbanilate and melatonin, both of which have been shown to be active in other systems.", "contents": "A new culture model facilitating rapid quantitative testing of mitotic spindle inhibition in mammalian cells. A new culture model, which facilitated both mass screening of potential anticancer drugs acting on microtubules and quantitative experiments with known \"antitubulins,\" was found to have the following advantages: use of mammalian cells (either transformed or not), simplicity of the techniques (phase-contrast microscopy or simple microscopy after Giemsa staining), and ease with which it lent itself to quantification. The model was based on the uniform multimicronucleation response induced by antitubulins in MO cells. The specificity (towards antitubulins) of this response was ascertained by the use of many substances, including most of the known antitubulins and a number of nonrelated cytostatic or cytotoxic compounds. The uniformity of the response was established with the use of time-lapse observation of large numbers of cells and quantitative approaches. The results obtained in this model with the standard antitubulins (colchicine, vinblastine, vincristine) showed similar effects. The major difference between colchicine and the Vinca alkaloids was that colchicine was less reversible, which might be an indication of stronger intracellular binding. The Vinca alkaloids acted synergistically with colchicine when threshold subactive doses were combined, although it is known that they bind at a different site on tubulins. A number of substances that have been claimed or were suspected to interfere with microtubules were tested. The results showed that the following substances were indeed active with MO cells: colchicine, vinblastine, vincristine, podophyllotoxin, rotenone, griseofulvin, mercaptoethanol, benomyl, methyl benzimidazol-2-yl carbamate, and R 17934. Compounds that were inactive on these mammalian cells in culture included isopropyl carbanilate and melatonin, both of which have been shown to be active in other systems."} {"id": "PMID:1255767", "title": "Radiotherapy of spontaneous fibrous connective-tissue sarcomas in animals.", "content": "The clinical records and follow-up data obtained over 13 years on the results of radiotherapy of spontaneous fibrous connective-tissue sarcomas in dogs, cats, and horses were reviewed. The results obtained from the treatment of fibrosarcomas and sarcoids of horses indicated that radiation administered with 60Co is important in the medical and surgical management of these tumors. Fibrous connective-tissue sarcomas in horses were radioresponsive. When radiotherapy was applied postoperatively, the probability of a 2-year cure approached 50% for all prescribed radiation doses of less than 2,000 to greater than 4,000 rads. If radiation doses of 4,500-6,000 rads were used, a 2-year cure rate may approach or exceed 60%.", "contents": "Radiotherapy of spontaneous fibrous connective-tissue sarcomas in animals. The clinical records and follow-up data obtained over 13 years on the results of radiotherapy of spontaneous fibrous connective-tissue sarcomas in dogs, cats, and horses were reviewed. The results obtained from the treatment of fibrosarcomas and sarcoids of horses indicated that radiation administered with 60Co is important in the medical and surgical management of these tumors. Fibrous connective-tissue sarcomas in horses were radioresponsive. When radiotherapy was applied postoperatively, the probability of a 2-year cure approached 50% for all prescribed radiation doses of less than 2,000 to greater than 4,000 rads. If radiation doses of 4,500-6,000 rads were used, a 2-year cure rate may approach or exceed 60%."} {"id": "PMID:1255768", "title": "Susceptibility of normal and transformed cell lines to cytostatic and cytocidal effects exerted by macrophages.", "content": "Activated, nonimmune macrophages exerted profound effects on the proliferation and viability of eukaryotic target cells in vitro. Pronounced macrophage-mediated cytostasis was exerted on every rapidly proliferating cell line examined, irrespective of transformation, species derivation, cell type, or growth characteristics. However, the magnitude of cytostasis effected differed markedly among the 40 cell lines tested. There was no evident correlation between susceptibility to cytostasis and degree of transformation. Transformed cell lines with high and with low malignant attributes were affected equally. A comparable pattern was discerned for cytocidal effects of macrophages, in which the susceptibility of transformed targets was independent of the degree of malignancy.", "contents": "Susceptibility of normal and transformed cell lines to cytostatic and cytocidal effects exerted by macrophages. Activated, nonimmune macrophages exerted profound effects on the proliferation and viability of eukaryotic target cells in vitro. Pronounced macrophage-mediated cytostasis was exerted on every rapidly proliferating cell line examined, irrespective of transformation, species derivation, cell type, or growth characteristics. However, the magnitude of cytostasis effected differed markedly among the 40 cell lines tested. There was no evident correlation between susceptibility to cytostasis and degree of transformation. Transformed cell lines with high and with low malignant attributes were affected equally. A comparable pattern was discerned for cytocidal effects of macrophages, in which the susceptibility of transformed targets was independent of the degree of malignancy."} {"id": "PMID:1255769", "title": "Effects of Rauscher leukemia virus infection on BALB/c mouse embryos.", "content": "The effects of Rauscher leukemia virus (R-MuLV) infection on BALB/c mouse embryos were described. In mice infected with R-MuLV 12 days before mating, there were no embryos 8 days after possible conception, whereas in those infected either 8 days or 1 day before mating, pregnancy was established. The most striking effect of R-MuLV infection on the microscopic properties of the embryos was vast \"apoptosis\" in the mesoderm. The XC test with trypsinized embryo cells showed numerous polykaryons, which suggested that active leukemia virus was present in the embryonal tissue. Indirect immunofluorescence studies with specific rabbit antiserum to R-MuLV demonstrated the presence of virus antigens in the embryonal tissue. Vast immunofluorescence was also found in trophoblastic cells and embryonal membranes. We concluded that R-MuLV in BALB/c mice was transmitted from mother to embryo through the placenta and thereby caused excessive cell death, especially in the mesoderm.", "contents": "Effects of Rauscher leukemia virus infection on BALB/c mouse embryos. The effects of Rauscher leukemia virus (R-MuLV) infection on BALB/c mouse embryos were described. In mice infected with R-MuLV 12 days before mating, there were no embryos 8 days after possible conception, whereas in those infected either 8 days or 1 day before mating, pregnancy was established. The most striking effect of R-MuLV infection on the microscopic properties of the embryos was vast \"apoptosis\" in the mesoderm. The XC test with trypsinized embryo cells showed numerous polykaryons, which suggested that active leukemia virus was present in the embryonal tissue. Indirect immunofluorescence studies with specific rabbit antiserum to R-MuLV demonstrated the presence of virus antigens in the embryonal tissue. Vast immunofluorescence was also found in trophoblastic cells and embryonal membranes. We concluded that R-MuLV in BALB/c mice was transmitted from mother to embryo through the placenta and thereby caused excessive cell death, especially in the mesoderm."} {"id": "PMID:1255770", "title": "Humoral antibody response and tumor transplantation resistance elicited by fetal tissues in mice.", "content": "Immune responses to fetal antigen immunization were studied in C57BL/6 (B6), C3H/HeN (C3H), and BALB/c (BALB) mice. In tests by the isotopic antiglobulin technique, the mice could be grouped in three classes according to their antibody responses: good responders (B6), poor responders (C3H), and nonresponders (BALB). In tumor transplantation experiments, protection against syngeneic tumor-cell challenge, after fetal tissue immunization, was observed only with B6 mice. In addition, experiments on B6 mice showed that resistance to tumor challenge after fetal tissue immunization depended on the quantitative expression of fetal antigens by the tumor cells. Our results indicated that, in addition to other well-known factors, the effectiveness of fetal tissue immunization in tumor-challenge resistance depended on both host responsiveness and the amount of fetal antigen expressed by the tumor cells.", "contents": "Humoral antibody response and tumor transplantation resistance elicited by fetal tissues in mice. Immune responses to fetal antigen immunization were studied in C57BL/6 (B6), C3H/HeN (C3H), and BALB/c (BALB) mice. In tests by the isotopic antiglobulin technique, the mice could be grouped in three classes according to their antibody responses: good responders (B6), poor responders (C3H), and nonresponders (BALB). In tumor transplantation experiments, protection against syngeneic tumor-cell challenge, after fetal tissue immunization, was observed only with B6 mice. In addition, experiments on B6 mice showed that resistance to tumor challenge after fetal tissue immunization depended on the quantitative expression of fetal antigens by the tumor cells. Our results indicated that, in addition to other well-known factors, the effectiveness of fetal tissue immunization in tumor-challenge resistance depended on both host responsiveness and the amount of fetal antigen expressed by the tumor cells."} {"id": "PMID:1255771", "title": "Leiomyomas and leiomyosarcomas of the kidney in 4-day-old BUF rats given methylazoxymethanol acetate intraperitoneally.", "content": "The effect of age and sex on the development of renal tumors was studied in inbred BUF male and female rats 4 days, 5, 8, 12, 24, or 52 weeks old. Methylazoxymethanol (MAM) acetate was injected ip (20 mg/kg body wt) once weekly for 9 weeks. Animals 52 weeks old died from hepatic and/or renal necrosis; however, animals of other ages survived 24-42 weeks. Female rats 4 days old were susceptible to the development of leiomyomas and leiomyosarcomas of the kidney, whereas 4-day-old male rats had a few leiomyomas. Adenomas and carcinomas of the kidney and nephroblastomas were not observed. It was concluded that the aglycone of cycasin, MAM, is important in the induction of leiomyosarcomas of the kidneys in 4-day-old rats.", "contents": "Leiomyomas and leiomyosarcomas of the kidney in 4-day-old BUF rats given methylazoxymethanol acetate intraperitoneally. The effect of age and sex on the development of renal tumors was studied in inbred BUF male and female rats 4 days, 5, 8, 12, 24, or 52 weeks old. Methylazoxymethanol (MAM) acetate was injected ip (20 mg/kg body wt) once weekly for 9 weeks. Animals 52 weeks old died from hepatic and/or renal necrosis; however, animals of other ages survived 24-42 weeks. Female rats 4 days old were susceptible to the development of leiomyomas and leiomyosarcomas of the kidney, whereas 4-day-old male rats had a few leiomyomas. Adenomas and carcinomas of the kidney and nephroblastomas were not observed. It was concluded that the aglycone of cycasin, MAM, is important in the induction of leiomyosarcomas of the kidneys in 4-day-old rats."} {"id": "PMID:1255772", "title": "Is Hodgkin's disease infectious? Discussion of an epidemiologic method used to impute that it is.", "content": "A method proposed by MacMahon for the differentiation between familial and environmental causes for disease has recently been applied to demonstrate an environmental etiology for Hodgkin's disease. It is shown that the method, which depends on the comparison of time-of-onset differences with age-at-onset differences for familial pairs with disease, is biased toward results suggestive of an environmental etiology when applied to data of the kind typically analyzed--data restricted to instances in which both members of a familial pair develop disease in a specified, limited time interval. Other features of such data are discussed.", "contents": "Is Hodgkin's disease infectious? Discussion of an epidemiologic method used to impute that it is. A method proposed by MacMahon for the differentiation between familial and environmental causes for disease has recently been applied to demonstrate an environmental etiology for Hodgkin's disease. It is shown that the method, which depends on the comparison of time-of-onset differences with age-at-onset differences for familial pairs with disease, is biased toward results suggestive of an environmental etiology when applied to data of the kind typically analyzed--data restricted to instances in which both members of a familial pair develop disease in a specified, limited time interval. Other features of such data are discussed."} {"id": "PMID:1255773", "title": "Effects of fasting on growth and glycolysis of the Ehrlich ascites tumor.", "content": "C57BL/6 male mice bearing the Ehrlich escites tumor were subjected to two schedules of intermittent starvation, and the effect on the tumor's growth and production of lactic acid was determined. Fasting resulted in a linear dose--response inhibition of tumor growth, but did not alter its lactic acid production.", "contents": "Effects of fasting on growth and glycolysis of the Ehrlich ascites tumor. C57BL/6 male mice bearing the Ehrlich escites tumor were subjected to two schedules of intermittent starvation, and the effect on the tumor's growth and production of lactic acid was determined. Fasting resulted in a linear dose--response inhibition of tumor growth, but did not alter its lactic acid production."} {"id": "PMID:1255774", "title": "Tumor-promoting activity of cigarette tar in rat skin exposed to irradiation.", "content": "A threefold increase (P=0.006) in the number of skin tumors induced by beta irradiation was demonstrated in rats after surface applications of cigarette tar. The effect appeared due to a tumor-promoting activity of the cigarette tar rather than to an additive tumorigenic effect of the two agents.", "contents": "Tumor-promoting activity of cigarette tar in rat skin exposed to irradiation. A threefold increase (P=0.006) in the number of skin tumors induced by beta irradiation was demonstrated in rats after surface applications of cigarette tar. The effect appeared due to a tumor-promoting activity of the cigarette tar rather than to an additive tumorigenic effect of the two agents."} {"id": "PMID:1255775", "title": "Enhanced growth rate of transplanted mammary adenocarcinoma induced in C3H mice by dietary linoleate.", "content": "Three-month-old C3H female mice were given injections of 5-mg pieces of mammary adenocarcinoma and were then fed diets that either were fat free or contained saturated fat (15% hydrogenated cottonseed oil) or linoleate (1-15% corn oil). After 6 weeks, the tumors in mice fed the linoleate diet weighed 3-4 times more than those in mice fed the fat-free or saturated-fat diets. Despite a linoleate-free diet, tumors contained appreciable amounts of linoleate and arachidonate (approximately 2 and 9% of the total fatty acids, respectively). When the level of dietary corn oil was increased from 1 to 15%, the linoleate content of the tumors increased from 4 to 18% of the total fatty acids. However, in these instances, the tumor arachidonate levels increased to maximum values even when the 1% corn oil diet was used. These observations showed that mammary tumor growth was depressed by a fat-free or saturated-fat diet and enhanced by dietary linoleate. Furthermore, they suggested that the growth rate was related to the arachidonate content rather than the linoleate content of the tumors.", "contents": "Enhanced growth rate of transplanted mammary adenocarcinoma induced in C3H mice by dietary linoleate. Three-month-old C3H female mice were given injections of 5-mg pieces of mammary adenocarcinoma and were then fed diets that either were fat free or contained saturated fat (15% hydrogenated cottonseed oil) or linoleate (1-15% corn oil). After 6 weeks, the tumors in mice fed the linoleate diet weighed 3-4 times more than those in mice fed the fat-free or saturated-fat diets. Despite a linoleate-free diet, tumors contained appreciable amounts of linoleate and arachidonate (approximately 2 and 9% of the total fatty acids, respectively). When the level of dietary corn oil was increased from 1 to 15%, the linoleate content of the tumors increased from 4 to 18% of the total fatty acids. However, in these instances, the tumor arachidonate levels increased to maximum values even when the 1% corn oil diet was used. These observations showed that mammary tumor growth was depressed by a fat-free or saturated-fat diet and enhanced by dietary linoleate. Furthermore, they suggested that the growth rate was related to the arachidonate content rather than the linoleate content of the tumors."} {"id": "PMID:1255776", "title": "Effect of leupeptin, a protease inhibitor, on induction of bladder tumors in rats by n-butyl-n-(4-hydroxybutyl)nitrosamine.", "content": "Leupeptin, isolated from Actinomycetes, is a potent and specific inhibitor of proteases. We found that the administration of leupeptin enhanced that size of urinary bladder tumors induced in rats by the oral administration of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). BBN was given as a 0.05% solution in the drinking water for 6 weeks, and then animals were fed a diet with or without 0.1% leupeptin for 30 weeks. The average weight of the bladders with tumors in rats fed a leupeptin diet was about eight times that of rats on a diet without leupeptin, though the incidences and average numbers of tumors in the bladders were similar in the two groups.", "contents": "Effect of leupeptin, a protease inhibitor, on induction of bladder tumors in rats by n-butyl-n-(4-hydroxybutyl)nitrosamine. Leupeptin, isolated from Actinomycetes, is a potent and specific inhibitor of proteases. We found that the administration of leupeptin enhanced that size of urinary bladder tumors induced in rats by the oral administration of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). BBN was given as a 0.05% solution in the drinking water for 6 weeks, and then animals were fed a diet with or without 0.1% leupeptin for 30 weeks. The average weight of the bladders with tumors in rats fed a leupeptin diet was about eight times that of rats on a diet without leupeptin, though the incidences and average numbers of tumors in the bladders were similar in the two groups."} {"id": "PMID:1255777", "title": "Antitumor activity of Corynebacterium parvum extracts.", "content": "Extracts of Corynebacterium parvum produced by mild hydrolysis of the whole organisms had antitumor activity if given iv 1 day before iv administration of fibrosarcoma cells or if given ip or sc in admixture with these cells. A lipid component seemed responsible for these effects. Unlike whole bacteria, they had little immunotherapeutic activity if given 3 days after sc tumor implantation unless absorbed onto latex. However, organisms treated with acid did not have any immunotherapeutic effect in this system either. The extracts, therefore, did have some antitumor activity, but full activity may depend on the integrity of the whole bacterium.", "contents": "Antitumor activity of Corynebacterium parvum extracts. Extracts of Corynebacterium parvum produced by mild hydrolysis of the whole organisms had antitumor activity if given iv 1 day before iv administration of fibrosarcoma cells or if given ip or sc in admixture with these cells. A lipid component seemed responsible for these effects. Unlike whole bacteria, they had little immunotherapeutic activity if given 3 days after sc tumor implantation unless absorbed onto latex. However, organisms treated with acid did not have any immunotherapeutic effect in this system either. The extracts, therefore, did have some antitumor activity, but full activity may depend on the integrity of the whole bacterium."} {"id": "PMID:1255778", "title": "Promoting effect of sodium deoxycholate on colon adenocarcinomas in germfree rats.", "content": "The promoting effect of sodium deoxycholate (DC) on colon carcinogenesis was studied in female F344 germfree rats. Animals received intrarectal (ir) instillations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 4 weeks (total dose, 16 mg/rat), then weekly ir doses of DC (total dose, 3 g/rat); the rats were autopsied 52 weeks after the first injection. DC increased the number of MNNG-induced colon adenocarcinomas. No tumors were in the colons of germfree rats given DC alone. It was concluded that DC (present in high concentrations in human stools) had a promoting effect on colon carcinogenesis in rats.", "contents": "Promoting effect of sodium deoxycholate on colon adenocarcinomas in germfree rats. The promoting effect of sodium deoxycholate (DC) on colon carcinogenesis was studied in female F344 germfree rats. Animals received intrarectal (ir) instillations of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) for 4 weeks (total dose, 16 mg/rat), then weekly ir doses of DC (total dose, 3 g/rat); the rats were autopsied 52 weeks after the first injection. DC increased the number of MNNG-induced colon adenocarcinomas. No tumors were in the colons of germfree rats given DC alone. It was concluded that DC (present in high concentrations in human stools) had a promoting effect on colon carcinogenesis in rats."} {"id": "PMID:1255779", "title": "Quantitative microscopy of epidermoid lung carcinoma: correlation with survival time.", "content": "Quantitative microscopy, including morphometry of tumor, stroma, and necrosis was used for the prognostication of pulmonary carcinoma. This was supplemented by the mitosis: necrobiosis ratio, reciprocal of cell count, and number of \"apoptosis\" bodies. Data for 15 short-term (4-19 mo) and 8 long-term (32-132 mo) survivors with epidermoid carcinoma were expressed as indexes. The morphometric index averaged 106.8 for short-term and 156.1 for long-term survivors, respectively. Addition of the other three indexes resulted in an average of 171.4 for short-term and 318.5 for long-term survivors. Morphometric index and the necrobiosis: mitosis ratio were of greater significance than the other two indexes. Discriminatory function analysis based on the weighted sum of the logarithms of the four indexes demonstrated their usefulness in classifying patients as short-term or long-term survivors. The error rate for the discriminant analysis was 3.5%.", "contents": "Quantitative microscopy of epidermoid lung carcinoma: correlation with survival time. Quantitative microscopy, including morphometry of tumor, stroma, and necrosis was used for the prognostication of pulmonary carcinoma. This was supplemented by the mitosis: necrobiosis ratio, reciprocal of cell count, and number of \"apoptosis\" bodies. Data for 15 short-term (4-19 mo) and 8 long-term (32-132 mo) survivors with epidermoid carcinoma were expressed as indexes. The morphometric index averaged 106.8 for short-term and 156.1 for long-term survivors, respectively. Addition of the other three indexes resulted in an average of 171.4 for short-term and 318.5 for long-term survivors. Morphometric index and the necrobiosis: mitosis ratio were of greater significance than the other two indexes. Discriminatory function analysis based on the weighted sum of the logarithms of the four indexes demonstrated their usefulness in classifying patients as short-term or long-term survivors. The error rate for the discriminant analysis was 3.5%."} {"id": "PMID:1255780", "title": "Burkitt's lymphoma in the Mengo Districts of Uganda: epidemiologic features and their relationship to malaria.", "content": "An epidemiologic study of 123 patients residing in the Mengo Districts of Uganda, with onset of symptoms of diagnosed Burkitt's lymphoma (BL) in the period 1959-68, revealed a substantial decline in incidence of BL during that decade. Other significant findings included differences by ethnic group in age of patient at onset of BL, a change in the proportions of patients by ethnic group over the decade, a lower incidence rate of BL in the countries of higher altitude, and a seasonal pattern of onset. There was no evidence of the time space clustering previously reported for BL in Uganda. The changing pattern of BL in the Mengo Districts was consistent with the hypothesis that severe malaria infection not only is important in the development of BL but also precipitates onset.", "contents": "Burkitt's lymphoma in the Mengo Districts of Uganda: epidemiologic features and their relationship to malaria. An epidemiologic study of 123 patients residing in the Mengo Districts of Uganda, with onset of symptoms of diagnosed Burkitt's lymphoma (BL) in the period 1959-68, revealed a substantial decline in incidence of BL during that decade. Other significant findings included differences by ethnic group in age of patient at onset of BL, a change in the proportions of patients by ethnic group over the decade, a lower incidence rate of BL in the countries of higher altitude, and a seasonal pattern of onset. There was no evidence of the time space clustering previously reported for BL in Uganda. The changing pattern of BL in the Mengo Districts was consistent with the hypothesis that severe malaria infection not only is important in the development of BL but also precipitates onset."} {"id": "PMID:1255781", "title": "Melanomas of the eye and other noncutaneous sites: epidemiologic aspects.", "content": "The Third National Cancer Survey, 1969-71, reported 432 patients with noncutaneous melanoma, 79% originating in the eye. As with skin melanoma, ocular tumors were more common in whites than blacks and predominated in females at younger ages and males after middle life. On the other hand, ocular melanoma did not show the strong North-South gradient seen with skin melanoma; this suggested no relation to sunlight exposure.", "contents": "Melanomas of the eye and other noncutaneous sites: epidemiologic aspects. The Third National Cancer Survey, 1969-71, reported 432 patients with noncutaneous melanoma, 79% originating in the eye. As with skin melanoma, ocular tumors were more common in whites than blacks and predominated in females at younger ages and males after middle life. On the other hand, ocular melanoma did not show the strong North-South gradient seen with skin melanoma; this suggested no relation to sunlight exposure."} {"id": "PMID:1255782", "title": "Correlation of in vivo malignancy with in vitro properties of human-mouse hybrid cells.", "content": "The in vivo tumorigenicity of malignant mouse-nonmalignant human somatic cell hybrids was correlated with the in vitro characteristics. The renal adenocarcinoma mouse cell line RAG and the normal, diploid human cell line Wl-38 were used as the fusion parents. Five independent RAG Wl 38 hybrid clones were tested for concanavalin A (Con A) agglutination patterns, in vitro invasiveness, and tumor formation in immunosuppressed mice. Tests on the parental lines showed that RAG cells agglutinated at much lower levels of Con A than the Wl-38 cells. RAG cells overgrew Wl-38 cells in the in vitro invasiveness assay. RAG cells readily formed tumors in untreated adult or young immunosuppressed mice, whereas the Wl-38 cells did not. The five hybrid clones were all similar, since they had Con A agglutination levels intermediate to those of both parents, though patterns were more \"tumor-like\", overgrew the Wl-38 cells in the invasiveness assay, and formed tumors in immunosuppressed mice.", "contents": "Correlation of in vivo malignancy with in vitro properties of human-mouse hybrid cells. The in vivo tumorigenicity of malignant mouse-nonmalignant human somatic cell hybrids was correlated with the in vitro characteristics. The renal adenocarcinoma mouse cell line RAG and the normal, diploid human cell line Wl-38 were used as the fusion parents. Five independent RAG Wl 38 hybrid clones were tested for concanavalin A (Con A) agglutination patterns, in vitro invasiveness, and tumor formation in immunosuppressed mice. Tests on the parental lines showed that RAG cells agglutinated at much lower levels of Con A than the Wl-38 cells. RAG cells overgrew Wl-38 cells in the in vitro invasiveness assay. RAG cells readily formed tumors in untreated adult or young immunosuppressed mice, whereas the Wl-38 cells did not. The five hybrid clones were all similar, since they had Con A agglutination levels intermediate to those of both parents, though patterns were more \"tumor-like\", overgrew the Wl-38 cells in the invasiveness assay, and formed tumors in immunosuppressed mice."} {"id": "PMID:1255783", "title": "Dianhydrogalactitol (NSC-132313): pharmacokinetics in normal and tumor-bearing rat brain and antitumor activity against three intracerebral rodent tumors.", "content": "Dianhydrogalactitol (DAG; NSC-132313), a hexitol epoxide, was used to treat intracerebral rodent tumors. DAG was most active against the murine ependymoblastoma [treated/controls (T/C)greater than 440%], less active against murine glioma 26 (T/C approximately 112-150%), and least active against rat 9L gliosarcoma (T/C approximately 100%). Application of a two-compartment open model for plasma disappearance of 14C-DAG in rats gave a volume of distribution at steady state of approximately 872 ml, a clearance of approximately 9.4 ml/minute, and an elimination constant of 0.025/minute. Entry of 14C-DAG was more rapid into the 9L tumor than into the normal brain. When a two-compartment series model for brain and tumor entry was applied, the t1/2 (half-time) for compartmental equilibrium was approximately 22 and 105 minutes in the brain, and 4 and 56 minutes in the 9L tumor. The drug rapidly entered the brain and tumor intracellular compartments. Binding to RNA was linear with time, and the absolute amount of binding was approximately six times greater for RNA than for DNA.", "contents": "Dianhydrogalactitol (NSC-132313): pharmacokinetics in normal and tumor-bearing rat brain and antitumor activity against three intracerebral rodent tumors. Dianhydrogalactitol (DAG; NSC-132313), a hexitol epoxide, was used to treat intracerebral rodent tumors. DAG was most active against the murine ependymoblastoma [treated/controls (T/C)greater than 440%], less active against murine glioma 26 (T/C approximately 112-150%), and least active against rat 9L gliosarcoma (T/C approximately 100%). Application of a two-compartment open model for plasma disappearance of 14C-DAG in rats gave a volume of distribution at steady state of approximately 872 ml, a clearance of approximately 9.4 ml/minute, and an elimination constant of 0.025/minute. Entry of 14C-DAG was more rapid into the 9L tumor than into the normal brain. When a two-compartment series model for brain and tumor entry was applied, the t1/2 (half-time) for compartmental equilibrium was approximately 22 and 105 minutes in the brain, and 4 and 56 minutes in the 9L tumor. The drug rapidly entered the brain and tumor intracellular compartments. Binding to RNA was linear with time, and the absolute amount of binding was approximately six times greater for RNA than for DNA."} {"id": "PMID:1255784", "title": "Pathogenesis of ascites in mice with peritoneal carcinomatosis.", "content": "For clarification of the mechanisms underlying formation of malignant ascites, alterations in lymphatic transport from the peritoneal cavity and in peritoneal capillary permeability to protein were studied sequentially in mice inoculated ip with Ehrlich-Lettre ascites tumor cells. All animals developed detectable ascites within 5-7 days of the injection. Diaphragmatic and retrosternal lymph vessels became radiopaque within 30 hours of the ip injection of radiopaque contrast material in control animals without ascites and in 12 experimental mice receiving contrast material 1-3 days after injection of tumor cells. No lymph vessels were opacified in 3 of 4 animals when contrast material was injected on day 5 or in any animal receiving contrast material on or after day 7 following the tumor cell injection. We determined alterations in peritoneal capillary permeability in the second group by measuring the concentration of iv injected Evans blue dye in eluates of sections of peritoneum and contiguous underlying tissue removed 3 hours after injection of dye. Permeability averaged 1.5 times normal (P = 0.02) by day 3 after tumor cell injection, 2 times normal by day 5, and 3 times normal by day 7; it remained at the final level. Although lymph drainage became impaired within 24 hours of the detection of ascites, a progressive increase in capillary permeability began 2 days earlier and was probably the predominant alteration in pathogenesis of the effusion.", "contents": "Pathogenesis of ascites in mice with peritoneal carcinomatosis. For clarification of the mechanisms underlying formation of malignant ascites, alterations in lymphatic transport from the peritoneal cavity and in peritoneal capillary permeability to protein were studied sequentially in mice inoculated ip with Ehrlich-Lettre ascites tumor cells. All animals developed detectable ascites within 5-7 days of the injection. Diaphragmatic and retrosternal lymph vessels became radiopaque within 30 hours of the ip injection of radiopaque contrast material in control animals without ascites and in 12 experimental mice receiving contrast material 1-3 days after injection of tumor cells. No lymph vessels were opacified in 3 of 4 animals when contrast material was injected on day 5 or in any animal receiving contrast material on or after day 7 following the tumor cell injection. We determined alterations in peritoneal capillary permeability in the second group by measuring the concentration of iv injected Evans blue dye in eluates of sections of peritoneum and contiguous underlying tissue removed 3 hours after injection of dye. Permeability averaged 1.5 times normal (P = 0.02) by day 3 after tumor cell injection, 2 times normal by day 5, and 3 times normal by day 7; it remained at the final level. Although lymph drainage became impaired within 24 hours of the detection of ascites, a progressive increase in capillary permeability began 2 days earlier and was probably the predominant alteration in pathogenesis of the effusion."} {"id": "PMID:1255785", "title": "Biologic effects of plant toxins and aflatoxins in rats.", "content": "After weaning, groups of rats were fed a semi-purified diet containing fiddlehead greens (the unfuried frond of the ostrich fern Matteuccia struthiopteris), mature bracken fern (Pteridium aquilinum), or cycad meal (Cycas circinalis), or this diet plus aflatoxin B1. The groups fed 1-10% fiddlehead greens for 70-73 weeks developed no tumors, whereas those fed mature bracken fern for 67 weeks developed small-bowel adenocarcinomas (3/17). Those fed 3% cycad meal for 64 weeks developed tumors of the liver (4/18), kidney (2/18), small bowel (1/18), and large bowel (6/18). Those given aflatoxin B1 and observed for 73 weeks developed liver tumors (11/15). Thus this study indicates that fiddlehead greens from M. struthiopteris are not toxic or carcinogenic.", "contents": "Biologic effects of plant toxins and aflatoxins in rats. After weaning, groups of rats were fed a semi-purified diet containing fiddlehead greens (the unfuried frond of the ostrich fern Matteuccia struthiopteris), mature bracken fern (Pteridium aquilinum), or cycad meal (Cycas circinalis), or this diet plus aflatoxin B1. The groups fed 1-10% fiddlehead greens for 70-73 weeks developed no tumors, whereas those fed mature bracken fern for 67 weeks developed small-bowel adenocarcinomas (3/17). Those fed 3% cycad meal for 64 weeks developed tumors of the liver (4/18), kidney (2/18), small bowel (1/18), and large bowel (6/18). Those given aflatoxin B1 and observed for 73 weeks developed liver tumors (11/15). Thus this study indicates that fiddlehead greens from M. struthiopteris are not toxic or carcinogenic."} {"id": "PMID:1255786", "title": "Protective effects of amphotericin B against spontaneous and transplantable murine tumors.", "content": "Two tumor systems were used to test prophylactic effects of amphotericin B (AmB). When 0.5 mg AmB was given ip every 2 weeks to AKR mice beginning at 8 weeks of age, the 50% tumor incidence for spontaneous lymphoma development was delayed 2-3 months. In the second tumor system, BALB/c mice received injections of either 20 or 50 mug AmB before receiving MOPC-315-C cells sc. The mice given the low dose of AmB demonstrated a decreased tumor incidence and a reduced tumor growth rate, when compared with controls. Opposite effects were found for the group administered the high dose; tumor incidence and rate of growth were increased.", "contents": "Protective effects of amphotericin B against spontaneous and transplantable murine tumors. Two tumor systems were used to test prophylactic effects of amphotericin B (AmB). When 0.5 mg AmB was given ip every 2 weeks to AKR mice beginning at 8 weeks of age, the 50% tumor incidence for spontaneous lymphoma development was delayed 2-3 months. In the second tumor system, BALB/c mice received injections of either 20 or 50 mug AmB before receiving MOPC-315-C cells sc. The mice given the low dose of AmB demonstrated a decreased tumor incidence and a reduced tumor growth rate, when compared with controls. Opposite effects were found for the group administered the high dose; tumor incidence and rate of growth were increased."} {"id": "PMID:1255787", "title": "Invasive behavior between sarcoma and fibroblast populations in cell culture.", "content": "The mutual invasion in culture of a population of standard fibroblasts (chick embryo) and a population of cells from a transplantable mouse sarcoma (MC)M, BAS/56, or 311) or of neontal mouse fibroblasts has been estimated quantitatively. We arranged the confrontation of the pairs of populations by placing primary explants near each other. After fixation, the distance the cells had migrated from each explant was sampled in the space between the explants where they met and at the sides of the explants where they migrated freely. Measurements of nuclear overlap and orientation were also made. In the sarcoma as in the fibroblast population, homologous contact inhibition of movement probably produced an oriented migration from the explants before the populations met. Abot 12-24 hours after, mutual invasion was considerably greater in the sarcoma versus fibroblast than in the fibroblast versus fibroblast experiments. It is proposed that this difference was due to a difference of heterologous contact inhibition in the two types of experiment.", "contents": "Invasive behavior between sarcoma and fibroblast populations in cell culture. The mutual invasion in culture of a population of standard fibroblasts (chick embryo) and a population of cells from a transplantable mouse sarcoma (MC)M, BAS/56, or 311) or of neontal mouse fibroblasts has been estimated quantitatively. We arranged the confrontation of the pairs of populations by placing primary explants near each other. After fixation, the distance the cells had migrated from each explant was sampled in the space between the explants where they met and at the sides of the explants where they migrated freely. Measurements of nuclear overlap and orientation were also made. In the sarcoma as in the fibroblast population, homologous contact inhibition of movement probably produced an oriented migration from the explants before the populations met. Abot 12-24 hours after, mutual invasion was considerably greater in the sarcoma versus fibroblast than in the fibroblast versus fibroblast experiments. It is proposed that this difference was due to a difference of heterologous contact inhibition in the two types of experiment."} {"id": "PMID:1255788", "title": "Further observations on the inhibition of tumor growth by Corynebacterium parvum with cyclophosphamide. II. Effect of cortisone acetate.", "content": "Studies from this laboratory have demonstrated that the administration of cyclophosphamide (CY) and Corynebacterium parvum (CP) over a prolonged time to C3H mice with established measurable tumors resulted in complete arrest of tumor growth as well as partial and complete regressions in many instances. A study of the effect of two different doses of cortisone acetate (CA), administered two or five times weekly, on the tumor inhibitory properties of this chemoimmunotherapeutic regimen indicated that the addition of a corticosteroid to the CY-CP combination did not alter its tumor-inhibitory properties. There was no significant change when CA was administered with CP; however, tumor inhibition was enhanced to a degree approaching statistical significance when CA was added to CY at dose levels of 1.5 and 2.5 mg twice weekly. These results demonstrated that it may be possible in treatment of humans to administer a steroid in combination with a chemoimmunotherapeutic regimen without inhibition of the regimen's antitumor effects.", "contents": "Further observations on the inhibition of tumor growth by Corynebacterium parvum with cyclophosphamide. II. Effect of cortisone acetate. Studies from this laboratory have demonstrated that the administration of cyclophosphamide (CY) and Corynebacterium parvum (CP) over a prolonged time to C3H mice with established measurable tumors resulted in complete arrest of tumor growth as well as partial and complete regressions in many instances. A study of the effect of two different doses of cortisone acetate (CA), administered two or five times weekly, on the tumor inhibitory properties of this chemoimmunotherapeutic regimen indicated that the addition of a corticosteroid to the CY-CP combination did not alter its tumor-inhibitory properties. There was no significant change when CA was administered with CP; however, tumor inhibition was enhanced to a degree approaching statistical significance when CA was added to CY at dose levels of 1.5 and 2.5 mg twice weekly. These results demonstrated that it may be possible in treatment of humans to administer a steroid in combination with a chemoimmunotherapeutic regimen without inhibition of the regimen's antitumor effects."} {"id": "PMID:1255789", "title": "Aflatoxin B; specific antibodies and their use in radioimmunoassay.", "content": "New Zealand White rabbits immunized with covalent conjugates prepared from polylysine and the O-carboxy-methyloxime derivatives of either aflatoxin B1 (AFB1) or an analogue, 5,7-dimethoxycyclopentenon (2,3-c) coumarin, produced antibodies that bind 3H-AFB1. The specificities of the antisera with respect to aflatoxins BI, B2a, G1, G2, Q1, P1, and some other structually related compounds were determined. Radioimmunoassays that can detect levels as low as 0.27 pmoles (0.06 ng) of AFB1-were used to analyze serum, urine, and crude extracts of corn and peanut supplemented with aflatoxin. In the foodstuffs, as little as 1 mug AFB1/kg was measured. The immunoassay was at least as sensitive and specific as other available analytic methods, but did not require the purification of samples by chromatography before analysis. The technique may be particularly useful in epidemiologic studies designed to study the possible relationship between chronic aflatoxin ingestion and cancer.", "contents": "Aflatoxin B; specific antibodies and their use in radioimmunoassay. New Zealand White rabbits immunized with covalent conjugates prepared from polylysine and the O-carboxy-methyloxime derivatives of either aflatoxin B1 (AFB1) or an analogue, 5,7-dimethoxycyclopentenon (2,3-c) coumarin, produced antibodies that bind 3H-AFB1. The specificities of the antisera with respect to aflatoxins BI, B2a, G1, G2, Q1, P1, and some other structually related compounds were determined. Radioimmunoassays that can detect levels as low as 0.27 pmoles (0.06 ng) of AFB1-were used to analyze serum, urine, and crude extracts of corn and peanut supplemented with aflatoxin. In the foodstuffs, as little as 1 mug AFB1/kg was measured. The immunoassay was at least as sensitive and specific as other available analytic methods, but did not require the purification of samples by chromatography before analysis. The technique may be particularly useful in epidemiologic studies designed to study the possible relationship between chronic aflatoxin ingestion and cancer."} {"id": "PMID:1255790", "title": "Metabolism of N-2-fluorenylacetamide in X/Gf mice: lack of correlation between biochemical interaction and carcinogenicity.", "content": "A comparative study of the metabolism of the carcinogen N-2-fluorenylacetamide by mice of the X/Gf strain (resistant to the tumorigenic action) and the NiH Swiss strain (susceptible to the tumorigenic action) showed slight but not outstanding differences in metabolic patterns. The activated metabolite N-hydroxy-N-2-fluorenylacetamide was excreted by both strains, and the levels of carcinogens or metabolites bound to liver macromolecular constituents were comparable in the X/Gf and NiH Swiss mice.", "contents": "Metabolism of N-2-fluorenylacetamide in X/Gf mice: lack of correlation between biochemical interaction and carcinogenicity. A comparative study of the metabolism of the carcinogen N-2-fluorenylacetamide by mice of the X/Gf strain (resistant to the tumorigenic action) and the NiH Swiss strain (susceptible to the tumorigenic action) showed slight but not outstanding differences in metabolic patterns. The activated metabolite N-hydroxy-N-2-fluorenylacetamide was excreted by both strains, and the levels of carcinogens or metabolites bound to liver macromolecular constituents were comparable in the X/Gf and NiH Swiss mice."} {"id": "PMID:1255792", "title": "Unusual cell junctional complexes in canine mammary adenoacanthomas.", "content": "Unusual cell junctional complexes were described in spontaneously arising adenoacanthomas of canine mammary glands. These junctional complexes were a manifestation of bidirectional differentiation of tumor cell membranes.", "contents": "Unusual cell junctional complexes in canine mammary adenoacanthomas. Unusual cell junctional complexes were described in spontaneously arising adenoacanthomas of canine mammary glands. These junctional complexes were a manifestation of bidirectional differentiation of tumor cell membranes."} {"id": "PMID:1255793", "title": "Cellular immune reaction to human malignant melanoma and breast carcinoma cells.", "content": "An in vitro microassay was used to study cytotoxic reactivity of lymphocytes of 19 patients with malignant melanoma, 8 patients with breast carcinoma, and 18 normal subjects on cell cultures of malignant melanoma and breast carcinoma. In each of the twelve experiments, peripheral blood lymphocytes from individuals with and without cancer were tested simultaneously on two or three different target cells. Cytotoxic reactivity, evaluated by a comparison of the number of target cells remaining after incubation with lymphocytes with those incubated with medium only, was found in 20 cancer patients (74%) and 13 individuals without cancer (72%). The strength of lymphocyte reactivity of the cancer and of the non-cancer group did not differ significantly. Of the 27 cancer patients, 8 were positive only on the homologous target cells, 7 only on the opposite cells, and 5 on both types; 7 were negative. Short-term melanoma cell cultures were more lysable than were established cell lines; however, no direct correlation between the growth rate during the test period and susceptibility to lysis was seen. The blood group of the lymphocyte donors had no influence on cytotoxic reactivity.", "contents": "Cellular immune reaction to human malignant melanoma and breast carcinoma cells. An in vitro microassay was used to study cytotoxic reactivity of lymphocytes of 19 patients with malignant melanoma, 8 patients with breast carcinoma, and 18 normal subjects on cell cultures of malignant melanoma and breast carcinoma. In each of the twelve experiments, peripheral blood lymphocytes from individuals with and without cancer were tested simultaneously on two or three different target cells. Cytotoxic reactivity, evaluated by a comparison of the number of target cells remaining after incubation with lymphocytes with those incubated with medium only, was found in 20 cancer patients (74%) and 13 individuals without cancer (72%). The strength of lymphocyte reactivity of the cancer and of the non-cancer group did not differ significantly. Of the 27 cancer patients, 8 were positive only on the homologous target cells, 7 only on the opposite cells, and 5 on both types; 7 were negative. Short-term melanoma cell cultures were more lysable than were established cell lines; however, no direct correlation between the growth rate during the test period and susceptibility to lysis was seen. The blood group of the lymphocyte donors had no influence on cytotoxic reactivity."} {"id": "PMID:1255791", "title": "Therapy of transplanted lymphomas.", "content": "Allogeneic cells or cell products containing murine leukemia virus were effective in curtailing growth of a transplanted CBA lymphoma, which was originally induced by Gross virus and then maintained by syngeneic cell passage. All allogeneic cells or products effective in therapy of this lymphoma expressed virus as tested by the XC cell in vitro infectivity assay. Some of the materials also expressed virus as assayed by oncogenicity in vivo. A therapeutic effect was not demonstrated with allogeneic cells or cell products laking these virus activities. Syngeneic lymphoma cells were ineffective. Protected animals did not develop lymphoma when rechallenged several months later. Mechanisms for this therapy with virus were proposed.", "contents": "Therapy of transplanted lymphomas. Allogeneic cells or cell products containing murine leukemia virus were effective in curtailing growth of a transplanted CBA lymphoma, which was originally induced by Gross virus and then maintained by syngeneic cell passage. All allogeneic cells or products effective in therapy of this lymphoma expressed virus as tested by the XC cell in vitro infectivity assay. Some of the materials also expressed virus as assayed by oncogenicity in vivo. A therapeutic effect was not demonstrated with allogeneic cells or cell products laking these virus activities. Syngeneic lymphoma cells were ineffective. Protected animals did not develop lymphoma when rechallenged several months later. Mechanisms for this therapy with virus were proposed."} {"id": "PMID:1255794", "title": "Racial and occupational variations in cancer of the testis: San Francisco, 1956-65.", "content": "During 1956-65, white and nonwhite San Francisco male residents did not have equal risks of developing testicular cancer. The lower risk observed for nonwhites could not be attributed entirely to genetic factors, since among whites a risk gradient seemed to correlate directly with broad socioeconomic indices such as occupation and census tract of residence. Although incidence rates for testicular cancer have progressively increased in the United States and now parallel rates in Danish towns and rural areas, they are still lower than rates observed in Copenhagen, where a \"technology\" effect has been postulated. In this perspective, the San Francisco findings are compatible with a hypothesis that certain occupational groups may have become epidemiologic indicators of testicular carcinogens in a changing environment.", "contents": "Racial and occupational variations in cancer of the testis: San Francisco, 1956-65. During 1956-65, white and nonwhite San Francisco male residents did not have equal risks of developing testicular cancer. The lower risk observed for nonwhites could not be attributed entirely to genetic factors, since among whites a risk gradient seemed to correlate directly with broad socioeconomic indices such as occupation and census tract of residence. Although incidence rates for testicular cancer have progressively increased in the United States and now parallel rates in Danish towns and rural areas, they are still lower than rates observed in Copenhagen, where a \"technology\" effect has been postulated. In this perspective, the San Francisco findings are compatible with a hypothesis that certain occupational groups may have become epidemiologic indicators of testicular carcinogens in a changing environment."} {"id": "PMID:1255795", "title": "Lymphocyte plasma membranes. VI. Surface antigens of lymphocytes in chronic lymphocytic leukemia.", "content": "Surface antigens from lymphocytes of patients with chronic lymphocytic leukemia (CLL) and from normal peripheral blood lymphocytes (PBL) were examined by radioimmunoassay; antisera to lymphocytes (ALS) were used to bind the labeled antigens. Cells from patients with CLL, normal PBL, thymus cells (THY), and cultured human lymphoblasts (CHL) were labeled by lactoperoxidase-catalyzed iodination. ALS (prepared against THY and CHL) were used to bind the labeled antigens solubilized in nonionic detergent. PBL resembled THY, but the CLL resembled CHL. Thus ALS(CHL) had greater potency for CLL antigens than for PBL antigens when compared to ALS(THY). Furthermore, the electrophoretic profiles of the immunoprecipitates from CLL cells revealed a peak of approximately 30,000-35,000 mol wt, which was not found for PBL or THY, but was associated with CHL.", "contents": "Lymphocyte plasma membranes. VI. Surface antigens of lymphocytes in chronic lymphocytic leukemia. Surface antigens from lymphocytes of patients with chronic lymphocytic leukemia (CLL) and from normal peripheral blood lymphocytes (PBL) were examined by radioimmunoassay; antisera to lymphocytes (ALS) were used to bind the labeled antigens. Cells from patients with CLL, normal PBL, thymus cells (THY), and cultured human lymphoblasts (CHL) were labeled by lactoperoxidase-catalyzed iodination. ALS (prepared against THY and CHL) were used to bind the labeled antigens solubilized in nonionic detergent. PBL resembled THY, but the CLL resembled CHL. Thus ALS(CHL) had greater potency for CLL antigens than for PBL antigens when compared to ALS(THY). Furthermore, the electrophoretic profiles of the immunoprecipitates from CLL cells revealed a peak of approximately 30,000-35,000 mol wt, which was not found for PBL or THY, but was associated with CHL."} {"id": "PMID:1255796", "title": "Mouse skin assay of condensate from smoking products other than tobacco.", "content": "The biologic activity of a smoking product other than tobacco (Cytrel) was compaed with that of an American-type blend of cigarette tobaccos by application of the smoke condensate (SC) to shaved mouse skin. In 4 nonsimultaneous experiments, SC's from the former were equivalent or lower in tumorigenicity than equal doses of those from the latter, studied simultaneously and under identical conditions; this was true for widely varying doses of SC's, ranging from 35 to 246 mg nonaqueous condensate (NAC) administered to each mouse/week for 63-92 weeks. The response to SC from smoking products other than tobacco ranged from a complete lack of epidermoid carcinomas and papillomas at the lower doses to an incidence of lesions in 25.3% of the animals at the highest dose. The SC from a typical American blend of tobaccos caused skin lesions in 18.7-39.1% of the animals. SC from type 324 Cytrel, applied at the even higher dose of 365 mg/mouse/week, caused papillomas or carcinomas in only 22.0% of the animals, as compared with 39.1% of mice after adminstration of 245 mg SC from the American blend of cigarette tobacco; this was the highest dose that could be achieved with a test material containing nicotine. SC from a 1:1 blend of Cytrel with cigarette tobacco produced considerably fewer skin lesions at the lower dose levels than did SC from tobacco. At the lowest dose of 35 mg/mouse/week, 2 and 18.7% of the animals had lesions, and at a 54-mg dose, 11.3 and 22.7% had lesions from the blend and tobacco samples, respectively. At an increased level (113 mg), the response was the same for the SC from a 1:1 blend and from cigarette tobacco. There existed an excellent dose-response relationship for SC from type 308 Cytrel tested at four dose levels: 8.4, 113, 246, and 383 mg NAC/mouse/week, with 0, 18.7, 25.3, and 57.7% of the animals exhibiting skin lesions, respectively. Based on the criteria inherent in the technique of \"mouse skin painting\", Cytrel variants appeared to be lower or equal in tumorigenicity than did cigarette tobacco.", "contents": "Mouse skin assay of condensate from smoking products other than tobacco. The biologic activity of a smoking product other than tobacco (Cytrel) was compaed with that of an American-type blend of cigarette tobaccos by application of the smoke condensate (SC) to shaved mouse skin. In 4 nonsimultaneous experiments, SC's from the former were equivalent or lower in tumorigenicity than equal doses of those from the latter, studied simultaneously and under identical conditions; this was true for widely varying doses of SC's, ranging from 35 to 246 mg nonaqueous condensate (NAC) administered to each mouse/week for 63-92 weeks. The response to SC from smoking products other than tobacco ranged from a complete lack of epidermoid carcinomas and papillomas at the lower doses to an incidence of lesions in 25.3% of the animals at the highest dose. The SC from a typical American blend of tobaccos caused skin lesions in 18.7-39.1% of the animals. SC from type 324 Cytrel, applied at the even higher dose of 365 mg/mouse/week, caused papillomas or carcinomas in only 22.0% of the animals, as compared with 39.1% of mice after adminstration of 245 mg SC from the American blend of cigarette tobacco; this was the highest dose that could be achieved with a test material containing nicotine. SC from a 1:1 blend of Cytrel with cigarette tobacco produced considerably fewer skin lesions at the lower dose levels than did SC from tobacco. At the lowest dose of 35 mg/mouse/week, 2 and 18.7% of the animals had lesions, and at a 54-mg dose, 11.3 and 22.7% had lesions from the blend and tobacco samples, respectively. At an increased level (113 mg), the response was the same for the SC from a 1:1 blend and from cigarette tobacco. There existed an excellent dose-response relationship for SC from type 308 Cytrel tested at four dose levels: 8.4, 113, 246, and 383 mg NAC/mouse/week, with 0, 18.7, 25.3, and 57.7% of the animals exhibiting skin lesions, respectively. Based on the criteria inherent in the technique of \"mouse skin painting\", Cytrel variants appeared to be lower or equal in tumorigenicity than did cigarette tobacco."} {"id": "PMID:1255797", "title": "Prognostic factors in canine mammary cancer.", "content": "From a follow-up study of dogs surgically treated for mammary cancer, ten characteristics were analyzed statistically with special reference to their association with prognosis (expressed as survival for 2 years). The interrelations among five of the characteristics were also tested. The histologic type (descending range in malignancy: sarcomas greater than simple carcinomas greater than complex carcinomas), mode of growth (highly infiltrating greater than moderately infiltrating greater than expansive), clinical stage of complex carcinomas (large tumors and/or tumors involving the skin or underlying tissue greater than small, well-defined tumors), and size (greater than 15 cm greater than 11-15 cm greater than 5-10 cm greater than 0-5 cm) were of definite prognostic importance. The histologic grade was of possible prognostic importance. Localization, type of surgical therapy (mastectomy, block-dissection), growth in lymph vessels, involvement of regional lymph nodes, and duration of symptoms before treatment were not important to prognosis. A comparison between the factors associated with the prognosis of canine and human mammary cancer showed many similarities. However, the involvement of regional lymph nodes, important in women, was not so in bitches.", "contents": "Prognostic factors in canine mammary cancer. From a follow-up study of dogs surgically treated for mammary cancer, ten characteristics were analyzed statistically with special reference to their association with prognosis (expressed as survival for 2 years). The interrelations among five of the characteristics were also tested. The histologic type (descending range in malignancy: sarcomas greater than simple carcinomas greater than complex carcinomas), mode of growth (highly infiltrating greater than moderately infiltrating greater than expansive), clinical stage of complex carcinomas (large tumors and/or tumors involving the skin or underlying tissue greater than small, well-defined tumors), and size (greater than 15 cm greater than 11-15 cm greater than 5-10 cm greater than 0-5 cm) were of definite prognostic importance. The histologic grade was of possible prognostic importance. Localization, type of surgical therapy (mastectomy, block-dissection), growth in lymph vessels, involvement of regional lymph nodes, and duration of symptoms before treatment were not important to prognosis. A comparison between the factors associated with the prognosis of canine and human mammary cancer showed many similarities. However, the involvement of regional lymph nodes, important in women, was not so in bitches."} {"id": "PMID:1255798", "title": "Histochemical patterns in early lesions and infiltrating adenocarcinomas induced in mouse duodenum by n-ethyl-n'-nitro-n-nitrosoguanidine.", "content": "Intravillous, microcrater, and macroscopic invasive lesions induced in the mouse duodenum by N-ethyl-N'-nitro-N-nitrosoguanidine were examined histochemically. The cells of these neoplastic lesions and the proliferative zones of the normal crypts showed similar staining reactions in leucine aminopeptidase, alkaline and acid phosphatases, adenosine 5'-triphosphatase, and glucose-6-phosphate dehydrogenase. However, a slight decrease in succinic dehydrogenase activity and a slight increase in lactic dehydrogenase activity were observed in the intravillous and microcrater lesions compared to the activity in the proliferative zones of the crypts. The neoplastic cells of these lesions showed no mucus secretion. We discussed the origin of the neoplastic lesions using these and other findings.", "contents": "Histochemical patterns in early lesions and infiltrating adenocarcinomas induced in mouse duodenum by n-ethyl-n'-nitro-n-nitrosoguanidine. Intravillous, microcrater, and macroscopic invasive lesions induced in the mouse duodenum by N-ethyl-N'-nitro-N-nitrosoguanidine were examined histochemically. The cells of these neoplastic lesions and the proliferative zones of the normal crypts showed similar staining reactions in leucine aminopeptidase, alkaline and acid phosphatases, adenosine 5'-triphosphatase, and glucose-6-phosphate dehydrogenase. However, a slight decrease in succinic dehydrogenase activity and a slight increase in lactic dehydrogenase activity were observed in the intravillous and microcrater lesions compared to the activity in the proliferative zones of the crypts. The neoplastic cells of these lesions showed no mucus secretion. We discussed the origin of the neoplastic lesions using these and other findings."} {"id": "PMID:1255799", "title": "Inconsistent response of B16 melanoma to BCG immunotherapy.", "content": "We evaluated the potential of the B16 melanoma of mice as a model system for BCG immunotherapy of malignant melanoma. We studied a variety of treatment protocols: a) BCG given simultaneously but separately with a small number of B16 cells significantly inhibited tumor growth in only three of eight experiments. b) BCG injected directly into the tumor stimulated tumor growth in three of three experiments; the stimulation was at least partially attributable to the nutrient medium in which the BCG was suspended. c) The B16 tumor was weakly immunogenic and the addition of BCG to a tumor cell vaccine offered little improvement in subsequent resistance to tumor cell challenge: d) In a model of postsurgical residual tumor, metastatic to regional lymph nodes, BCG and tumor cell vaccination did not alter the development of nodal metastases. The B16 melanoma was not a useful model system for BCG immunotherapy, because the tumor inhibition was feeble, inconsistent, and not associated with augmented tumor immunity.", "contents": "Inconsistent response of B16 melanoma to BCG immunotherapy. We evaluated the potential of the B16 melanoma of mice as a model system for BCG immunotherapy of malignant melanoma. We studied a variety of treatment protocols: a) BCG given simultaneously but separately with a small number of B16 cells significantly inhibited tumor growth in only three of eight experiments. b) BCG injected directly into the tumor stimulated tumor growth in three of three experiments; the stimulation was at least partially attributable to the nutrient medium in which the BCG was suspended. c) The B16 tumor was weakly immunogenic and the addition of BCG to a tumor cell vaccine offered little improvement in subsequent resistance to tumor cell challenge: d) In a model of postsurgical residual tumor, metastatic to regional lymph nodes, BCG and tumor cell vaccination did not alter the development of nodal metastases. The B16 melanoma was not a useful model system for BCG immunotherapy, because the tumor inhibition was feeble, inconsistent, and not associated with augmented tumor immunity."} {"id": "PMID:1255800", "title": "Intrasplenic tumor formation in the syrian hamster (Mesocricetus auratus) after tracheal implants and treatment with diethylnitrosamine.", "content": "In two simultaneous experiments (A and B), tracheal tissue from 25 young Syrian hamsters was implanted in their mothers' spleens. In A, after tracheas from 3-week-old untreated donor offspring were implanted into their mothers, the mothers received 18 mg diethylnitrosamine (DEN)/kg body weight, sc, twice weekly for 20 weeks. Thereafter, the implants were removed and transferred to the spleens of other untreated offspring that were then similarly treated with DEN for 20 weeks. In B, the procedure was similar except that the donor offspring were pretreated with DEN for 20 weeks, beginning at the age of 8 weeks. The average treatment time for the implants in experiment A was 65 weeks; in B, 44 weeks. In A, only four implants demonstrated a papilloma or a papillary polyp. In B, such neoplasms developed after a much shorter treatment time, and in three cases, squamous cell carcinomas with invasive growth in to the splenic pulp were formed.", "contents": "Intrasplenic tumor formation in the syrian hamster (Mesocricetus auratus) after tracheal implants and treatment with diethylnitrosamine. In two simultaneous experiments (A and B), tracheal tissue from 25 young Syrian hamsters was implanted in their mothers' spleens. In A, after tracheas from 3-week-old untreated donor offspring were implanted into their mothers, the mothers received 18 mg diethylnitrosamine (DEN)/kg body weight, sc, twice weekly for 20 weeks. Thereafter, the implants were removed and transferred to the spleens of other untreated offspring that were then similarly treated with DEN for 20 weeks. In B, the procedure was similar except that the donor offspring were pretreated with DEN for 20 weeks, beginning at the age of 8 weeks. The average treatment time for the implants in experiment A was 65 weeks; in B, 44 weeks. In A, only four implants demonstrated a papilloma or a papillary polyp. In B, such neoplasms developed after a much shorter treatment time, and in three cases, squamous cell carcinomas with invasive growth in to the splenic pulp were formed."} {"id": "PMID:1255801", "title": "Immunostimulation of highly immunogenic target tumor cells by lymphoid cells in vitro.", "content": "A highly immunogenic mouse tumor was studied with the use of microcytotoxicity test, performed at lymphoid cell:target tumor cell ratios ranging from 1:1 to 1,000:1 at various times during tumour growth and after tumor excision. Although the tumor was highly immunogenic, in vitro lymphoid cell-mediated cytotoxicity was shown only with lymphoid cells from hyperimmunized mice, i.e., mice that had \"seen\" the tumor more than once. Instead, the lymphoid cells harvested 2 and 3 weeks after tumor inoculation, as well as after excision of the tumor, stimulated the target cells. At 4 weeks after inoculation of the tumor, there appeared to be neither stimulation nor inhibition of the target tumor cells, though at this point the growth of this highly immunogenic tumor had been arrested in vivo.", "contents": "Immunostimulation of highly immunogenic target tumor cells by lymphoid cells in vitro. A highly immunogenic mouse tumor was studied with the use of microcytotoxicity test, performed at lymphoid cell:target tumor cell ratios ranging from 1:1 to 1,000:1 at various times during tumour growth and after tumor excision. Although the tumor was highly immunogenic, in vitro lymphoid cell-mediated cytotoxicity was shown only with lymphoid cells from hyperimmunized mice, i.e., mice that had \"seen\" the tumor more than once. Instead, the lymphoid cells harvested 2 and 3 weeks after tumor inoculation, as well as after excision of the tumor, stimulated the target cells. At 4 weeks after inoculation of the tumor, there appeared to be neither stimulation nor inhibition of the target tumor cells, though at this point the growth of this highly immunogenic tumor had been arrested in vivo."} {"id": "PMID:1255802", "title": "Exogenous estrogens and breast cancer in women with natural menopause.", "content": "Age, age at menopause, and calendar year at menopause were controlled as factors related to estrogen use. Data on 90 breast cancer patients and 83 conrols--all of whom had a natural menopause--showed no relationship between breast cancer and estrogen usage after the start of menopause symptoms.", "contents": "Exogenous estrogens and breast cancer in women with natural menopause. Age, age at menopause, and calendar year at menopause were controlled as factors related to estrogen use. Data on 90 breast cancer patients and 83 conrols--all of whom had a natural menopause--showed no relationship between breast cancer and estrogen usage after the start of menopause symptoms."} {"id": "PMID:1255803", "title": "Inhibition of cell-mediated cytotoxicity against tumor-associated antigens by suppressor cells from tumor-bearing mice.", "content": "Spleen cells from mice bearing primary tumours induced by Moloney strain of murine sarcoma virus (M-MuSV) strongly inhibited the in vitro generation of specific secondary cell-mediated cytotoxic response of spleen cells from M-MusV regressor mice. These suppressor cells were resistant to treatment with anti-theta serum and complement or to X-irradiation. It appeared that suppressor cells may have had a role in limiting the host's immune response against tumor growth.", "contents": "Inhibition of cell-mediated cytotoxicity against tumor-associated antigens by suppressor cells from tumor-bearing mice. Spleen cells from mice bearing primary tumours induced by Moloney strain of murine sarcoma virus (M-MuSV) strongly inhibited the in vitro generation of specific secondary cell-mediated cytotoxic response of spleen cells from M-MusV regressor mice. These suppressor cells were resistant to treatment with anti-theta serum and complement or to X-irradiation. It appeared that suppressor cells may have had a role in limiting the host's immune response against tumor growth."} {"id": "PMID:1255804", "title": "Murine colon adenocarcinomas: methods for selective culture in vitro.", "content": "Two murine colon adenocarcinoma cell lines were established from primary cultures. The MCA-38 cell line was begun by treatment of the primary culture with trypsin to remove the fibroblastoid elements. The MCA-36 epithelial cells were sensitive to trypsin; therefore, the growth medium of MCA-36 primary cultures was augmented with collagenase to release the tumor-cell elements from the fibroblast network. These tumor elements were dissociated with trypsin and placed in tissue culture. Each cell line was cultured for at least 10 passages in vitro and gave rise to tumors when reimplanted in vivo.", "contents": "Murine colon adenocarcinomas: methods for selective culture in vitro. Two murine colon adenocarcinoma cell lines were established from primary cultures. The MCA-38 cell line was begun by treatment of the primary culture with trypsin to remove the fibroblastoid elements. The MCA-36 epithelial cells were sensitive to trypsin; therefore, the growth medium of MCA-36 primary cultures was augmented with collagenase to release the tumor-cell elements from the fibroblast network. These tumor elements were dissociated with trypsin and placed in tissue culture. Each cell line was cultured for at least 10 passages in vitro and gave rise to tumors when reimplanted in vivo."} {"id": "PMID:1255823", "title": "Gas gangrene complicating limb trauma.", "content": "A consecutive series of 18 patients with clostridial myonecrosis has been reviewed. The two deaths were attributed to other causes. A treatment regimen including repeated debridement and excision of all non-viable tissue, and therapeutic antibiotics is outlined. Hyperbaric oxygenation has been omitted from our treatment program.", "contents": "Gas gangrene complicating limb trauma. A consecutive series of 18 patients with clostridial myonecrosis has been reviewed. The two deaths were attributed to other causes. A treatment regimen including repeated debridement and excision of all non-viable tissue, and therapeutic antibiotics is outlined. Hyperbaric oxygenation has been omitted from our treatment program."} {"id": "PMID:1255825", "title": "Radiographic detectability of occipital and temporal-parietal fractures induced in cadaver heads.", "content": "Diagnostic performance based on a double-blind evaluation of test and control radiographs produced from nine different fractured cadaver skulls was compiled for six radiologists. The data resulting from two different diagnostic tasks were analyzed statistically for accuracy and confirmed interpretability including an assessment of task-related performance differences. Performance was found to be relatively independent of differences among radiologists and lesion location. Little overall correlation was found to exist between demonstrated ability to detect lesions radiographically, and visual confirmation of known lesions from the same films. These results suggest that overall performance was probably limited by a number of undefined clinical factors which influence the amount of meaningful information available from the resulting radiographs. The distribution of these degrading influences was not uniform within the population sampled so that certain radiographs proved to be particularly misleading when considered in terms of their apparent diagnostic value. As a result, even relatively large depressed fractures were in some instances considered radiographically uninterpretable.", "contents": "Radiographic detectability of occipital and temporal-parietal fractures induced in cadaver heads. Diagnostic performance based on a double-blind evaluation of test and control radiographs produced from nine different fractured cadaver skulls was compiled for six radiologists. The data resulting from two different diagnostic tasks were analyzed statistically for accuracy and confirmed interpretability including an assessment of task-related performance differences. Performance was found to be relatively independent of differences among radiologists and lesion location. Little overall correlation was found to exist between demonstrated ability to detect lesions radiographically, and visual confirmation of known lesions from the same films. These results suggest that overall performance was probably limited by a number of undefined clinical factors which influence the amount of meaningful information available from the resulting radiographs. The distribution of these degrading influences was not uniform within the population sampled so that certain radiographs proved to be particularly misleading when considered in terms of their apparent diagnostic value. As a result, even relatively large depressed fractures were in some instances considered radiographically uninterpretable."} {"id": "PMID:1255826", "title": "Turnover of amino acids in sepsis and starvation: Effect of glucose infusion.", "content": "The catabolism of glucose and amino acids has been studied in the normal, the fasted, and the fasted septic dog. The fasted septic dog oxidized more glucose and alanine, and had more gluconeogenesis from alanine and the five tritiated amino acids--glutamate, threonine, phenylalanine, leucine, and valine--as compared to the normal and equally fasted dog. Thus the total body protein catabolic state was characterized in biochemical terms. In contrast, following glucose infusion, the fasted septic animal responded much like the fasted animal in terms of decreased animo acid gluconeogenesis and decreased plasma concentrations of amino acids, fats and fat products, but considerably increased the oxidation of alanine. The increased alanine oxidation appeared to be primarily related to increased tissue clearance and increased plasma concentration. There was some suggestive evidence for enhanced oxidation of the tritiated amino acids including leucine and valine during glucose infusion. The protein catabolic state secondary to this sort of sepsis in dogs only on per os fluid support appears to be best characterized as a glucose catabolic state with alanine being oxidized directly. Such states are known to be ones of enhanced metabolic rate secondary to enhanced synthetic processes generally. This is probably related to enhanced sympathetic nervous system release of glucagon with insulin being normally responsive to glucose because of a normal plasma epinephrine.", "contents": "Turnover of amino acids in sepsis and starvation: Effect of glucose infusion. The catabolism of glucose and amino acids has been studied in the normal, the fasted, and the fasted septic dog. The fasted septic dog oxidized more glucose and alanine, and had more gluconeogenesis from alanine and the five tritiated amino acids--glutamate, threonine, phenylalanine, leucine, and valine--as compared to the normal and equally fasted dog. Thus the total body protein catabolic state was characterized in biochemical terms. In contrast, following glucose infusion, the fasted septic animal responded much like the fasted animal in terms of decreased animo acid gluconeogenesis and decreased plasma concentrations of amino acids, fats and fat products, but considerably increased the oxidation of alanine. The increased alanine oxidation appeared to be primarily related to increased tissue clearance and increased plasma concentration. There was some suggestive evidence for enhanced oxidation of the tritiated amino acids including leucine and valine during glucose infusion. The protein catabolic state secondary to this sort of sepsis in dogs only on per os fluid support appears to be best characterized as a glucose catabolic state with alanine being oxidized directly. Such states are known to be ones of enhanced metabolic rate secondary to enhanced synthetic processes generally. This is probably related to enhanced sympathetic nervous system release of glucagon with insulin being normally responsive to glucose because of a normal plasma epinephrine."} {"id": "PMID:1255827", "title": "Significance of the electrocardiogram in heart contusion due to blunt trauma.", "content": "In a series of 24 patients with major blunt chest trauma, 11 presented evidence of heart injury upon re-examination of serial ECGs and four were confirmed at autopsy. The clinical diagnosis had been recorded in only one patient. In every case of closed chest trauma, regardless of the degree of visible injury, cardiac injury must be suspected. A presumptive diagnosis is then made, usually on the basis of ECG changes, which cannot be ruled out by any other cause. Even in some cases with normal ECGs the clinician's suspicion is the only guide. With a presumptive diagnosis made, the patient is treated as is any patient with an irritable myocardium; bedrest, avoidance of conditions which may precipitate arrhythmias, and of fluid overload, and treatment of these complications as they arise. Anticoagulants are usually avoided. Followup for long periods is indicated, because of the occasional emergence of chronic constrictive pericarditis or ventricular aneurysm.", "contents": "Significance of the electrocardiogram in heart contusion due to blunt trauma. In a series of 24 patients with major blunt chest trauma, 11 presented evidence of heart injury upon re-examination of serial ECGs and four were confirmed at autopsy. The clinical diagnosis had been recorded in only one patient. In every case of closed chest trauma, regardless of the degree of visible injury, cardiac injury must be suspected. A presumptive diagnosis is then made, usually on the basis of ECG changes, which cannot be ruled out by any other cause. Even in some cases with normal ECGs the clinician's suspicion is the only guide. With a presumptive diagnosis made, the patient is treated as is any patient with an irritable myocardium; bedrest, avoidance of conditions which may precipitate arrhythmias, and of fluid overload, and treatment of these complications as they arise. Anticoagulants are usually avoided. Followup for long periods is indicated, because of the occasional emergence of chronic constrictive pericarditis or ventricular aneurysm."} {"id": "PMID:1255828", "title": "The surgical management of hepatic trauma.", "content": "The personal experience of 179 patients with hepatic injuries is reviewed by the author. Difficulties in diagnosis and other problems encountered are discussed. The methods of management of the injuries and his operative technique are discussed. The increasing incidence of violence and large-scale civil disturbances coupled with fast automobiles have shown the changing concept in the type of injuries and the need for more aggressive treatment.", "contents": "The surgical management of hepatic trauma. The personal experience of 179 patients with hepatic injuries is reviewed by the author. Difficulties in diagnosis and other problems encountered are discussed. The methods of management of the injuries and his operative technique are discussed. The increasing incidence of violence and large-scale civil disturbances coupled with fast automobiles have shown the changing concept in the type of injuries and the need for more aggressive treatment."} {"id": "PMID:1255829", "title": "Chain saw vs. face: another hazard of mechanized progress.", "content": "Serious facial injuries can occur as the result of upward recoil of a chain saw into the operator's face. Six such cases have been discussed and the mechanism of injury as well as possible means of prevention presented.", "contents": "Chain saw vs. face: another hazard of mechanized progress. Serious facial injuries can occur as the result of upward recoil of a chain saw into the operator's face. Six such cases have been discussed and the mechanism of injury as well as possible means of prevention presented."} {"id": "PMID:1255830", "title": "Retained intrapulmonary bullet presenting with bronchial obstruction.", "content": "A patient is presented who demonstrated migration of a retained intrapulmonary bullet 7 years after injury. This resulted in bronchial occlusion and post-obstructive lung infection without apparent hemoptysis. Lobectomy is considered the operative procedure of choice for this condition.", "contents": "Retained intrapulmonary bullet presenting with bronchial obstruction. A patient is presented who demonstrated migration of a retained intrapulmonary bullet 7 years after injury. This resulted in bronchial occlusion and post-obstructive lung infection without apparent hemoptysis. Lobectomy is considered the operative procedure of choice for this condition."} {"id": "PMID:1255832", "title": "Complete avulsion of the renal pedicle with survival: case reports and literature review.", "content": "Two cases of complete avulsion of the renal pedicle with survival are presented, and the nine previous cases in the available world's literature are reviewed. The young age of these patients and frequent association with trauma to other organs are discussed. Because of the common absence of hematuria, an intravenous pyelogram should be performed in all patients with significant nonpenetrating abdominal trauma, and a renal arteriogram is indicated if nonvisualization is present. A plea for immediate surgery is made, with consideration of vascular reconstruction. (See Addendum, p. 162).", "contents": "Complete avulsion of the renal pedicle with survival: case reports and literature review. Two cases of complete avulsion of the renal pedicle with survival are presented, and the nine previous cases in the available world's literature are reviewed. The young age of these patients and frequent association with trauma to other organs are discussed. Because of the common absence of hematuria, an intravenous pyelogram should be performed in all patients with significant nonpenetrating abdominal trauma, and a renal arteriogram is indicated if nonvisualization is present. A plea for immediate surgery is made, with consideration of vascular reconstruction. (See Addendum, p. 162)."} {"id": "PMID:1255833", "title": "The quantitative swab culture and smear: A quick, simple method for determining the number of viable aerobic bacteria on open wounds.", "content": "The quantitative swab culture is a reliable method for quantifying the number of viable bacteria colonizing open wounds. For open wounds in burn patients, the swab bacterial count is linearly related to biopsy quantification of viable bacteria in the underlying tissue. This technique is simple and requires no surgical manipulation of the wound. For a wound of uniform appearance, the standard deviation of a single swab culture from the mean log bacterial count for a series of cultures from widely spaced areas on the wound is +/- 0.85 logs; 95% confidence limits are +/- 1.7 logs from the mean. A Gram-stained smear from a wound swab requires less than 10 minutes to prepare. Visualization of bacteria on the smear indicates that 106 or more bacteria per swab are present. The value of the smear and swab techniques for predicting safe wound closure may be inferred from the published reports of others and the direct relationship between the swab and biopsy counts of viable bacteria for open wounds.", "contents": "The quantitative swab culture and smear: A quick, simple method for determining the number of viable aerobic bacteria on open wounds. The quantitative swab culture is a reliable method for quantifying the number of viable bacteria colonizing open wounds. For open wounds in burn patients, the swab bacterial count is linearly related to biopsy quantification of viable bacteria in the underlying tissue. This technique is simple and requires no surgical manipulation of the wound. For a wound of uniform appearance, the standard deviation of a single swab culture from the mean log bacterial count for a series of cultures from widely spaced areas on the wound is +/- 0.85 logs; 95% confidence limits are +/- 1.7 logs from the mean. A Gram-stained smear from a wound swab requires less than 10 minutes to prepare. Visualization of bacteria on the smear indicates that 106 or more bacteria per swab are present. The value of the smear and swab techniques for predicting safe wound closure may be inferred from the published reports of others and the direct relationship between the swab and biopsy counts of viable bacteria for open wounds."} {"id": "PMID:1255834", "title": "Entrapment of the tibialis anterior tendon as a cause of nonunion in fractures of the distal tibia.", "content": "Three cases of nonunion of a fracture of the distal third of the tibia are reported. The cause of the nonunion in all three cases was the entrapment of the tibialis anterior tendon between the bone ends. This has not been previously reported as a specific cause of nonunion of the distal shaft of the tibia. This paper draws attention to this occurrence as a possible cause of nonunion in this area especially if the fracture is of the oblique type with an anterior spike at the distal end of the proximal fracture, with the line of fracture running parallel to the line of the tendon of the tibialis anterior. We suggest that fractures of this type should be treated early by internal fixation in view of the complications that can occur, such as nonunion, atrophy, or even complete rupture of the tendon of tibialis anterior, leading to a residual equinus deformity.", "contents": "Entrapment of the tibialis anterior tendon as a cause of nonunion in fractures of the distal tibia. Three cases of nonunion of a fracture of the distal third of the tibia are reported. The cause of the nonunion in all three cases was the entrapment of the tibialis anterior tendon between the bone ends. This has not been previously reported as a specific cause of nonunion of the distal shaft of the tibia. This paper draws attention to this occurrence as a possible cause of nonunion in this area especially if the fracture is of the oblique type with an anterior spike at the distal end of the proximal fracture, with the line of fracture running parallel to the line of the tendon of the tibialis anterior. We suggest that fractures of this type should be treated early by internal fixation in view of the complications that can occur, such as nonunion, atrophy, or even complete rupture of the tendon of tibialis anterior, leading to a residual equinus deformity."} {"id": "PMID:1255835", "title": "The strength and failure characteristics of rat medial collateral ligaments.", "content": "Traumatic loading of the knee joint in man occurs at strain rates ranging from 0.5-1,500 m/m/sec. Experiments on the medial collateral ligament of rats demonstrate that the mode of failure is a function of the strain rate. Avulsions occurred more often at low rates; ligament tearing occurred more often at high rates.", "contents": "The strength and failure characteristics of rat medial collateral ligaments. Traumatic loading of the knee joint in man occurs at strain rates ranging from 0.5-1,500 m/m/sec. Experiments on the medial collateral ligament of rats demonstrate that the mode of failure is a function of the strain rate. Avulsions occurred more often at low rates; ligament tearing occurred more often at high rates."} {"id": "PMID:1255836", "title": "Traumatic dislocation of hip joint with fracture of shaft of femur on the same side.", "content": "Four cases of traumatic dislocation of the hip joint with fracture of the shaft of femur on the same side, and one case of bilateral hip joint dislocation with a fracture of shaft of femur on one side are reported. Pitfalls in diagnosis and hazards of delayed treatment are emphasized. Methods of treatment are outlined. Complications such as avascular necrosis of the head of the femur and sciatic nerve palsy are discussed. Avascular necrosis of the head of the femur is not inevitable even after reduction of the joint has been delayed for several days.", "contents": "Traumatic dislocation of hip joint with fracture of shaft of femur on the same side. Four cases of traumatic dislocation of the hip joint with fracture of the shaft of femur on the same side, and one case of bilateral hip joint dislocation with a fracture of shaft of femur on one side are reported. Pitfalls in diagnosis and hazards of delayed treatment are emphasized. Methods of treatment are outlined. Complications such as avascular necrosis of the head of the femur and sciatic nerve palsy are discussed. Avascular necrosis of the head of the femur is not inevitable even after reduction of the joint has been delayed for several days."} {"id": "PMID:1255837", "title": "Use of 133xenon in early diagnosis of inhalation injury.", "content": "133Xenon lung scanning post-thermal injury was used to detect inhalation injury in 86 patients admitted to the United States Army Institute of Surgical Research during 1974. Inhalation injury was indicated by the 37 (43%) positive scans. Based on all available clinicopathologic evidence, 11 (13%) of the scans were erroneous with seven (8%) falsely positive and four (5%) falsely negative. Eighty-six per cent of the scans were \"appropriate.\" Addition of bronchoscopy and/or pulmonary function testing appeared to improve diagnostic accuracy. By using any pair of tests, falsely negative diagnoses were virtually eliminated. Inhalation injury, as expected, had an adverse effect on survival rates. The group of patients whose expected mortality lay between 40 and 59% were most notably affected. One hundred per cent (five of five) of those with inhalation injury died; only one of eight without inhalation injury died.", "contents": "Use of 133xenon in early diagnosis of inhalation injury. 133Xenon lung scanning post-thermal injury was used to detect inhalation injury in 86 patients admitted to the United States Army Institute of Surgical Research during 1974. Inhalation injury was indicated by the 37 (43%) positive scans. Based on all available clinicopathologic evidence, 11 (13%) of the scans were erroneous with seven (8%) falsely positive and four (5%) falsely negative. Eighty-six per cent of the scans were \"appropriate.\" Addition of bronchoscopy and/or pulmonary function testing appeared to improve diagnostic accuracy. By using any pair of tests, falsely negative diagnoses were virtually eliminated. Inhalation injury, as expected, had an adverse effect on survival rates. The group of patients whose expected mortality lay between 40 and 59% were most notably affected. One hundred per cent (five of five) of those with inhalation injury died; only one of eight without inhalation injury died."} {"id": "PMID:1255838", "title": "Lateral collateral ligament ankle injuries in young athletic individuals.", "content": "1. Eleven cases of surgical repair of acute tears of the capsule, anterior talo-fibular, and calcaneo-fibular ligaments of the ankle in young athletic individuals are reported. 2. Diagnosis was made by clinical examination and stress X-rays and confirmed by arthrography in selected cases. All of the ligament ruptures were visualized at surgery. 3. Post-surgery, all of the patients had a stable ankle and were able to return to vigorous athletic endeavors without disability. 4. This study lends support to the impression that surgical repair of severe lateral collateral ankle ligament injuries in young athletic individuals leads to a functionally and mechanically stable ankle able to withstand severe stress without disability.", "contents": "Lateral collateral ligament ankle injuries in young athletic individuals. 1. Eleven cases of surgical repair of acute tears of the capsule, anterior talo-fibular, and calcaneo-fibular ligaments of the ankle in young athletic individuals are reported. 2. Diagnosis was made by clinical examination and stress X-rays and confirmed by arthrography in selected cases. All of the ligament ruptures were visualized at surgery. 3. Post-surgery, all of the patients had a stable ankle and were able to return to vigorous athletic endeavors without disability. 4. This study lends support to the impression that surgical repair of severe lateral collateral ankle ligament injuries in young athletic individuals leads to a functionally and mechanically stable ankle able to withstand severe stress without disability."} {"id": "PMID:1255839", "title": "Jailhouse burns.", "content": "Twelve thermally injured patients were admitted to the burn ward of the University of Cincinnati Medical Center from penal institutions in the past six years. Six case histories were reviewed. The mortality rate was 66% and there were some with pulmonary complications. The problem of fires and burns in locked facilities is reviewed and some methods of prevention discussed.", "contents": "Jailhouse burns. Twelve thermally injured patients were admitted to the burn ward of the University of Cincinnati Medical Center from penal institutions in the past six years. Six case histories were reviewed. The mortality rate was 66% and there were some with pulmonary complications. The problem of fires and burns in locked facilities is reviewed and some methods of prevention discussed."} {"id": "PMID:1255840", "title": "Delayed appearance of traumatic ventral hernia: a case report.", "content": "An unusual traumatic ventral hernia is reported, observed 6 months after its presumed cause. The delay in diagnosis, the benign appearance of the abdomen in the supine position, and the necessity for marlex mesh prosthetic repair in a large traumatic defect are all unusual features. Following repair the patient has remained asymptomatic.", "contents": "Delayed appearance of traumatic ventral hernia: a case report. An unusual traumatic ventral hernia is reported, observed 6 months after its presumed cause. The delay in diagnosis, the benign appearance of the abdomen in the supine position, and the necessity for marlex mesh prosthetic repair in a large traumatic defect are all unusual features. Following repair the patient has remained asymptomatic."} {"id": "PMID:1255841", "title": "Triceps brachii rupture: case report.", "content": "A 44-year-old man has been seen by the present authors, apparently the third reported case of triceps brachii rupture. He had had bilateral nephrectomies one year earlier and since then has been medicated with Dilantin for grand mal seizures which followed hypovolemia during dialysis. A grand mal seizure immediately preceded the patient's right triceps brachii rupture and other multiple orthopaedic injuries. Following repair of the tendon defect the patient regained an active range of motion. The possible relationship of tendon rupture and avulsion to primary and secondary hyperparathyroidism is discussed.", "contents": "Triceps brachii rupture: case report. A 44-year-old man has been seen by the present authors, apparently the third reported case of triceps brachii rupture. He had had bilateral nephrectomies one year earlier and since then has been medicated with Dilantin for grand mal seizures which followed hypovolemia during dialysis. A grand mal seizure immediately preceded the patient's right triceps brachii rupture and other multiple orthopaedic injuries. Following repair of the tendon defect the patient regained an active range of motion. The possible relationship of tendon rupture and avulsion to primary and secondary hyperparathyroidism is discussed."} {"id": "PMID:1255845", "title": "Recovery of the accumulation ability of thiomethyl-beta-galactoside in Escherichia coli after bacteriophage T4 infection.", "content": "Effects of UV-irridiated and unirradiated T4 phage infection on the beta-galactoside accumulation ability in Eschericia coli have been examined by the use of 14C-labeled thiomethyl-beta-galactoside (TMG). Under conditions where a synchronous adsorption of phage takes place, the cellular ability for TMG accumulation is found to be largely inhibited immediately after phage adsorption, but it recovers with time to a new level, which is dependent on the multiplicity of infection. When cells are infected with UV-irradiated T4 at the same multiplicity as that of unirradiated phage, the cellular accumulation ability is more severely inhibited and there is no recovery from the inhibition. The recovery process in T4-infected cells is mostly sensitive to puromycin. These results suggest that the initial inhibition of the TMG accumulation ability is probably caused by the adsorption of phage coats, and the subsequent restoration occurs through the action of a phage-directed protein(s). In the recovery process, no new transport system appears to be involved. The restored ability of TMG accumulation is resistant to the action of superinfecting UV phage. However, different mechanisms appear to be operating in T4-infected cells for the establishment of resistance to ghosts and for the recovery from the phage coat-induced inhibition.", "contents": "Recovery of the accumulation ability of thiomethyl-beta-galactoside in Escherichia coli after bacteriophage T4 infection. Effects of UV-irridiated and unirradiated T4 phage infection on the beta-galactoside accumulation ability in Eschericia coli have been examined by the use of 14C-labeled thiomethyl-beta-galactoside (TMG). Under conditions where a synchronous adsorption of phage takes place, the cellular ability for TMG accumulation is found to be largely inhibited immediately after phage adsorption, but it recovers with time to a new level, which is dependent on the multiplicity of infection. When cells are infected with UV-irradiated T4 at the same multiplicity as that of unirradiated phage, the cellular accumulation ability is more severely inhibited and there is no recovery from the inhibition. The recovery process in T4-infected cells is mostly sensitive to puromycin. These results suggest that the initial inhibition of the TMG accumulation ability is probably caused by the adsorption of phage coats, and the subsequent restoration occurs through the action of a phage-directed protein(s). In the recovery process, no new transport system appears to be involved. The restored ability of TMG accumulation is resistant to the action of superinfecting UV phage. However, different mechanisms appear to be operating in T4-infected cells for the establishment of resistance to ghosts and for the recovery from the phage coat-induced inhibition."} {"id": "PMID:1255846", "title": "Sequence of methylated nucleotides at the 5'-terminus of adenovirus-specific RNA.", "content": "RNA labeled with [methyl-3H] methionine and [14C]uridine was isolated from the cytoplasm of adenovirus-infected cells and purified by poly(U)-Sepharose chromatography and hybridization to filters containing immobilized adeovirus DNA. Analysis by dimethyl sulfoxide-sucrose gradient sedimentation suggested that the major mRNA species were methylated. 7-Methylguanosine was identified at the 5'-terminus of the advenovirus-specific RNA and could be removed by periodate oxidation and beta-elimination. Structures of the type m7G(5')ppp(5')Nm containing the unusual nucleoside N6, O2'-dimethyladenosine, and smaller amounts of 2'-O-methyladenosine were isolated by DEAE-cellulose chromatography after P1 nuclease digestion of the RNA. Evidence for some 5'-terminal sequences, m7G(5')ppp(5')m6AmpNm, with additional 2'-O-methylribonucleosides was also obtained. A base-methylated nucleoside, N6-methyladenosine, is located within the RNA chain and is released as a mononucleotide by alkali hydrolysis.", "contents": "Sequence of methylated nucleotides at the 5'-terminus of adenovirus-specific RNA. RNA labeled with [methyl-3H] methionine and [14C]uridine was isolated from the cytoplasm of adenovirus-infected cells and purified by poly(U)-Sepharose chromatography and hybridization to filters containing immobilized adeovirus DNA. Analysis by dimethyl sulfoxide-sucrose gradient sedimentation suggested that the major mRNA species were methylated. 7-Methylguanosine was identified at the 5'-terminus of the advenovirus-specific RNA and could be removed by periodate oxidation and beta-elimination. Structures of the type m7G(5')ppp(5')Nm containing the unusual nucleoside N6, O2'-dimethyladenosine, and smaller amounts of 2'-O-methyladenosine were isolated by DEAE-cellulose chromatography after P1 nuclease digestion of the RNA. Evidence for some 5'-terminal sequences, m7G(5')ppp(5')m6AmpNm, with additional 2'-O-methylribonucleosides was also obtained. A base-methylated nucleoside, N6-methyladenosine, is located within the RNA chain and is released as a mononucleotide by alkali hydrolysis."} {"id": "PMID:1255847", "title": "Genetic analysis of adenovirus type 2 III. Temperature sensitivity of processing viral proteins.", "content": "Using sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis of [35S]methionine-labeled adenovirus type 2-infected KB cell extracts, a total of 23 virus-induced polypeptides was detected. This technique was applied to the analysis of the temperature-sensitive mutant, ts 1, which has previously been shown to be defective in a late function. By means of pulse-chase experiments, ts 1 was shown to be defective in the processing of the precursor polypeptide (Pre VII) to the major core protein VII. Two other putative precursor polypeptides, Va (27K) and Vb (24K), were also not processed. Thus, the ts 1 mutation blocked the appearance of six post-translational clevage products, i. e., polypeptides VI, VII, VIII, X, XI, and XII. All of these polypeptides are virion components. Processing was temperature sensitive in a shift-up experiment, whereas it was normal in a shift-down experiment. The kinetics of the temperature-shift experiments suggested that infectious virus could be recovered if enough time is provided for processing to take place. Processing was not inhibited by cycloheximide. The analysis of purified virus particles and empty shells (TCs) revealed the presence of the precursor and putative precursor polypeptides Pre-VII, Va and Vb, instead of their cleavage products, in both types of particles. Based on these results we propose that the ts 1 gene codes for or regulates an endoprotease which is responsible for the completion of the last step in virus maturation, that is, the conversion of \"young virions\" into mature infectious virions by a series of maturation cleavages.", "contents": "Genetic analysis of adenovirus type 2 III. Temperature sensitivity of processing viral proteins. Using sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis of [35S]methionine-labeled adenovirus type 2-infected KB cell extracts, a total of 23 virus-induced polypeptides was detected. This technique was applied to the analysis of the temperature-sensitive mutant, ts 1, which has previously been shown to be defective in a late function. By means of pulse-chase experiments, ts 1 was shown to be defective in the processing of the precursor polypeptide (Pre VII) to the major core protein VII. Two other putative precursor polypeptides, Va (27K) and Vb (24K), were also not processed. Thus, the ts 1 mutation blocked the appearance of six post-translational clevage products, i. e., polypeptides VI, VII, VIII, X, XI, and XII. All of these polypeptides are virion components. Processing was temperature sensitive in a shift-up experiment, whereas it was normal in a shift-down experiment. The kinetics of the temperature-shift experiments suggested that infectious virus could be recovered if enough time is provided for processing to take place. Processing was not inhibited by cycloheximide. The analysis of purified virus particles and empty shells (TCs) revealed the presence of the precursor and putative precursor polypeptides Pre-VII, Va and Vb, instead of their cleavage products, in both types of particles. Based on these results we propose that the ts 1 gene codes for or regulates an endoprotease which is responsible for the completion of the last step in virus maturation, that is, the conversion of \"young virions\" into mature infectious virions by a series of maturation cleavages."} {"id": "PMID:1255848", "title": "Isolation and characterization of Caulobacter crecentus bacteriophage phi Cd1.", "content": "A DNA-containing bacteriophage, phiCd1, was isolated from sewage and shown to infect both stalked and swarmer cells of Caulobacter crescentus strain CB13B1a. phiCd1 is a small, icosohedral bacteriophage, 60 nm in diameter, which possesses a short, noncontractile tail, 10 to 12 nm in length. The bacteriophage particle is composed of at least eight structural proteins. phiCd1 nucleic acid exists as a linear duplex of DNA as judged by: (i) thermal denaturation (Tm), (ii) CsCl density gradient centrifugation, and (iii) chemical analysis of its base composition. The DNA is 61% guanosine plus cytosine, has a buoyant density in CsCl of 1.721 +/- 0.001 g/cm3, and denatures sharply at 78.5 C in 0.1 SSC (standard saline citrate) buffer. The S20, w value for the DNA is 34.3 +/- 0.1S as compared with T7 DNA, indicating a molecular weight of about 29 x 10(6).", "contents": "Isolation and characterization of Caulobacter crecentus bacteriophage phi Cd1. A DNA-containing bacteriophage, phiCd1, was isolated from sewage and shown to infect both stalked and swarmer cells of Caulobacter crescentus strain CB13B1a. phiCd1 is a small, icosohedral bacteriophage, 60 nm in diameter, which possesses a short, noncontractile tail, 10 to 12 nm in length. The bacteriophage particle is composed of at least eight structural proteins. phiCd1 nucleic acid exists as a linear duplex of DNA as judged by: (i) thermal denaturation (Tm), (ii) CsCl density gradient centrifugation, and (iii) chemical analysis of its base composition. The DNA is 61% guanosine plus cytosine, has a buoyant density in CsCl of 1.721 +/- 0.001 g/cm3, and denatures sharply at 78.5 C in 0.1 SSC (standard saline citrate) buffer. The S20, w value for the DNA is 34.3 +/- 0.1S as compared with T7 DNA, indicating a molecular weight of about 29 x 10(6)."} {"id": "PMID:1255849", "title": "Functional empty capsid precursors produced by lambda mutant defective for late lambda DNA replication.", "content": "This report described lambda phage morphogenesis in a mutant system in which the normal pathways for late phage DNA (concatemer) synthesis are blocked and early (monomeric circular) DNA replication products accumulate. As shown earlier (Dawson et al., 1975) under these conditions, late proteins are synthesized and assembled into headlike structures. These structures that accumulate in the mutant are empty, suggesting the monomeric circular DNA molecules cannot be encapsulated. The present results show that crude extracts of induced lysogens of the mutant contain the complementation activities of preheads (the empty precursors to DNA-filled heads), tails, and DNA terminigenerating protein(s). Sucrose gradients of these crude extracts yield fractions containing prehead activity in relative amounts expected from the concentration of late proteins and empty structures. Furthermore, the proteins present in these fractions coelectrophorese with the known capsid proteins of preheads, and empty structures that look like preheads are observed in electron microscope examination of samples from the fractions. Based on our biological, biochemical, and electron microscope analyses, we conclude that the empty structures that accumulate in the induced lysogen of the mutant are normal preheads, which could become filled phage heads if DNA of the appropriate structure (i.e., \"late DNA\") were available.", "contents": "Functional empty capsid precursors produced by lambda mutant defective for late lambda DNA replication. This report described lambda phage morphogenesis in a mutant system in which the normal pathways for late phage DNA (concatemer) synthesis are blocked and early (monomeric circular) DNA replication products accumulate. As shown earlier (Dawson et al., 1975) under these conditions, late proteins are synthesized and assembled into headlike structures. These structures that accumulate in the mutant are empty, suggesting the monomeric circular DNA molecules cannot be encapsulated. The present results show that crude extracts of induced lysogens of the mutant contain the complementation activities of preheads (the empty precursors to DNA-filled heads), tails, and DNA terminigenerating protein(s). Sucrose gradients of these crude extracts yield fractions containing prehead activity in relative amounts expected from the concentration of late proteins and empty structures. Furthermore, the proteins present in these fractions coelectrophorese with the known capsid proteins of preheads, and empty structures that look like preheads are observed in electron microscope examination of samples from the fractions. Based on our biological, biochemical, and electron microscope analyses, we conclude that the empty structures that accumulate in the induced lysogen of the mutant are normal preheads, which could become filled phage heads if DNA of the appropriate structure (i.e., \"late DNA\") were available."} {"id": "PMID:1255850", "title": "Early gene expression in bacteriophage T7. I. In vivo synthesis, inactivation, and translational utilization of early mRNA's.", "content": "In vivo decay rates for the individual T7 early mRNA species were determined. The physical half-lives, measured at 37 C, range from 1.1 min for gene 0.7 RNA to 4.5 min for gene 0.3 RNA. Physical half-lives, as observed after rifampin inhibition of RNA synthesis and polyacylamide electrophoresis of RNAs, are approximately 30% longer than functional half-lives, as observed by 14C-labeled amino acid uptake into individual T7 early proteins. The different RNA species are synthesized at grossly different rates, 0.3 RNA at four times the rate of 1.0 RNA, 0.7 RNA at twice the rate, and 1.1 and 1.3 RNAs at about the same or a slightly lower rate than 1.0 RNA. Rho-factor-mediated termination of transcription behind genes 0.3, 0.7, and perhaps behind 1.0 is inferred from these data. The in vivo translational utilization of the individual T7 early-message species was found to vary by not more than a factor of 2.", "contents": "Early gene expression in bacteriophage T7. I. In vivo synthesis, inactivation, and translational utilization of early mRNA's. In vivo decay rates for the individual T7 early mRNA species were determined. The physical half-lives, measured at 37 C, range from 1.1 min for gene 0.7 RNA to 4.5 min for gene 0.3 RNA. Physical half-lives, as observed after rifampin inhibition of RNA synthesis and polyacylamide electrophoresis of RNAs, are approximately 30% longer than functional half-lives, as observed by 14C-labeled amino acid uptake into individual T7 early proteins. The different RNA species are synthesized at grossly different rates, 0.3 RNA at four times the rate of 1.0 RNA, 0.7 RNA at twice the rate, and 1.1 and 1.3 RNAs at about the same or a slightly lower rate than 1.0 RNA. Rho-factor-mediated termination of transcription behind genes 0.3, 0.7, and perhaps behind 1.0 is inferred from these data. The in vivo translational utilization of the individual T7 early-message species was found to vary by not more than a factor of 2."} {"id": "PMID:1255851", "title": "Replication process of the parvovirus H-1 V. Isolation and characterization of temperature-sensitive H-1 mutants.", "content": "Two temperature-sensitive mutants of the parvovirus H-1 have been isolated and characterized. These mutants are distinguishable by the immunofluorescent staining of cells infected by them and by the thermolability of their hemagglutinins. Under restrictive conditions both mutants synthesize a missense capsid protein defective in hemmaglutination. Synthesis of the viral DNA strand was shown to be diminished for both wild-type virus and these mutants at the restrictive temperature of 39.5 C, but the mutants were more defective than the wild type at the less restrictive temperature of 38 C. Replicative form DNA replication was not decreased in these mutants. It is proposed that H-1 requires one of the capsid proteins for the synthesis of the single-stranded progeny DNA.", "contents": "Replication process of the parvovirus H-1 V. Isolation and characterization of temperature-sensitive H-1 mutants. Two temperature-sensitive mutants of the parvovirus H-1 have been isolated and characterized. These mutants are distinguishable by the immunofluorescent staining of cells infected by them and by the thermolability of their hemagglutinins. Under restrictive conditions both mutants synthesize a missense capsid protein defective in hemmaglutination. Synthesis of the viral DNA strand was shown to be diminished for both wild-type virus and these mutants at the restrictive temperature of 39.5 C, but the mutants were more defective than the wild type at the less restrictive temperature of 38 C. Replicative form DNA replication was not decreased in these mutants. It is proposed that H-1 requires one of the capsid proteins for the synthesis of the single-stranded progeny DNA."} {"id": "PMID:1255852", "title": "Purification and properties of bacteriophage phi X 174 gene D product.", "content": "Bacteriophage phi X 174 gene D product, a protein required for single-stranded DNA synthesis by the phage, has been purified to near homogeneity. The protein is very abundant; approximately 10(5) monomers are present per infected cell when lysis is delayed. The protein has a monomer molecular weight of 15,200 and is normally a tetramer; however, it can form very large aggregates at high concentrations. Amino acid analysis shows an excess of arginine over lysine and a relatively high number of nonpolar residues. The protein carries a net negative charge at neutral pH. The first eight amino acids of the protein sequence have been determined; they are Ser-Gln-Val-Thr-Glu-Gln-Arg-Val. The carboxy-terminal residue is methionine. The protein has not yet been shown to bind directly to any single-stranded DNA; it does not adsorb to denatured calf thymus DNA-cellulose.", "contents": "Purification and properties of bacteriophage phi X 174 gene D product. Bacteriophage phi X 174 gene D product, a protein required for single-stranded DNA synthesis by the phage, has been purified to near homogeneity. The protein is very abundant; approximately 10(5) monomers are present per infected cell when lysis is delayed. The protein has a monomer molecular weight of 15,200 and is normally a tetramer; however, it can form very large aggregates at high concentrations. Amino acid analysis shows an excess of arginine over lysine and a relatively high number of nonpolar residues. The protein carries a net negative charge at neutral pH. The first eight amino acids of the protein sequence have been determined; they are Ser-Gln-Val-Thr-Glu-Gln-Arg-Val. The carboxy-terminal residue is methionine. The protein has not yet been shown to bind directly to any single-stranded DNA; it does not adsorb to denatured calf thymus DNA-cellulose."} {"id": "PMID:1255853", "title": "In vitro replication of cowpea mosaic virus RNA. II. Solubilization of membrane-bound replicase and the partial purification of the solubilized enzyme.", "content": "A method for the solubilization of membrane-bound Cowpea mosaic virus RNA replicase has been developed by bypassing the use of detergents. Solubilization has been achieved by washing the 31,000 x g-pellet containing the bound replicase with a Mg2+-deficient buffer. This procedure had several advantages as compared to treatments with nonionic or ionic detergents: (i) the solubilized enzyme was stable at 4 C, (ii) more than 80% of the replicase could be solubilized without loss of total enzyme activity, (iii) the replicase was rather selectively released resulting in a two- to threefold increase in specific activity per se, and (iv) most of the green color from chloroplast fragments present in the crude replicase fraction remained membrane bound resulting in only slightly colored preparations of solubilized enzyme. The solubilized replicase has been further purified by DEAE-Bio Gel column chromatography. RNA synthesis directed by the DEAE-purified enzyme was template dependent and proceeded at a linear rate for at least 9 h.", "contents": "In vitro replication of cowpea mosaic virus RNA. II. Solubilization of membrane-bound replicase and the partial purification of the solubilized enzyme. A method for the solubilization of membrane-bound Cowpea mosaic virus RNA replicase has been developed by bypassing the use of detergents. Solubilization has been achieved by washing the 31,000 x g-pellet containing the bound replicase with a Mg2+-deficient buffer. This procedure had several advantages as compared to treatments with nonionic or ionic detergents: (i) the solubilized enzyme was stable at 4 C, (ii) more than 80% of the replicase could be solubilized without loss of total enzyme activity, (iii) the replicase was rather selectively released resulting in a two- to threefold increase in specific activity per se, and (iv) most of the green color from chloroplast fragments present in the crude replicase fraction remained membrane bound resulting in only slightly colored preparations of solubilized enzyme. The solubilized replicase has been further purified by DEAE-Bio Gel column chromatography. RNA synthesis directed by the DEAE-purified enzyme was template dependent and proceeded at a linear rate for at least 9 h."} {"id": "PMID:1255854", "title": "Biochemical, biophysical, and biological properties of densonucleosis virus. I. Structural proteins.", "content": "The polypeptide composition of highly purified densonucleosis virus was studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The viral proteins showed a different behavior in sodium dodecyl sulfate-gels in comparison with the marker proteins. Therefore, the molecular weights were estimated by analyzing the retardation of the electrophoretic mobility of these proteins in gels with increasing polyacrylamide concentrations. Four structural proteins with molecular weights of 49,000, 58,500, 69,000, and 98,000 were found, ant they were designated p49, p59, p69, and p98, respectively. There are several indications that p98 is a dimer of p49. The relative quantity of the structural proteins in a virion suggests that at least p49 (accounting for +/-70% of total protein mass) is a capsid protein and that there will be 12 capsomers per virion.", "contents": "Biochemical, biophysical, and biological properties of densonucleosis virus. I. Structural proteins. The polypeptide composition of highly purified densonucleosis virus was studied by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The viral proteins showed a different behavior in sodium dodecyl sulfate-gels in comparison with the marker proteins. Therefore, the molecular weights were estimated by analyzing the retardation of the electrophoretic mobility of these proteins in gels with increasing polyacrylamide concentrations. Four structural proteins with molecular weights of 49,000, 58,500, 69,000, and 98,000 were found, ant they were designated p49, p59, p69, and p98, respectively. There are several indications that p98 is a dimer of p49. The relative quantity of the structural proteins in a virion suggests that at least p49 (accounting for +/-70% of total protein mass) is a capsid protein and that there will be 12 capsomers per virion."} {"id": "PMID:1255855", "title": "Red system of bacteriophage lambda complements the growth of a bacteriophage T1 gene 4 mutant.", "content": "The ability of phage lambda to complement the growth of T1am23, a T1 gene 4 mutant with a DNA arrest phenotype, has been shown to require both lambda Red functions, redX and redB. lambdagam function, however, is not required. Therefore, the lambda Red function can substitute for T1 gene 4 function. However, T1+ does not substitute for lambda Red in allowing lambda to grow in a polA host.", "contents": "Red system of bacteriophage lambda complements the growth of a bacteriophage T1 gene 4 mutant. The ability of phage lambda to complement the growth of T1am23, a T1 gene 4 mutant with a DNA arrest phenotype, has been shown to require both lambda Red functions, redX and redB. lambdagam function, however, is not required. Therefore, the lambda Red function can substitute for T1 gene 4 function. However, T1+ does not substitute for lambda Red in allowing lambda to grow in a polA host."} {"id": "PMID:1255856", "title": "Gene 32 protein of bacteriophage T4 moderates the activities of the T4 gene 46/47-controlled nuclease and of the Escherichia coli RecBC nuclease in vivo.", "content": "Genes 46 and 47 of phage T4 control a nuclease that is required for genetic recombination and may act similarly to the Escherichia coli RecBC nuclease. In vivo, the nucleolytic activities of both of these nucleases must be moderated so that recombining DNA intermediates are not destroyed. We conclude from our present experiments that the phage T4 gene 32 protein, specifically its C-terminal domain, participates in such moderation. We have investigated DNA degradation in different gene 32 and gene 32/46 mutants under conditions that are completely restrictive for progeny production in all the mutants. Under these conditions, DNA of those gene 32 mutants in which the C-terminal domain of the protein is not synthesized or is modified is degraded to acid-soluble material. T4 gene 46 or E. coli recB mutations reduce such degradation; together they abolish it completely. By contrast, single gene 32 mutants which produce an unaltered C-terminal domain show little or no degradation of their DNA. Residual protection against nucleases is unrelated to residual primary DNA replication or to overproduction of the mutant peptides in the different gene 32 mutants.", "contents": "Gene 32 protein of bacteriophage T4 moderates the activities of the T4 gene 46/47-controlled nuclease and of the Escherichia coli RecBC nuclease in vivo. Genes 46 and 47 of phage T4 control a nuclease that is required for genetic recombination and may act similarly to the Escherichia coli RecBC nuclease. In vivo, the nucleolytic activities of both of these nucleases must be moderated so that recombining DNA intermediates are not destroyed. We conclude from our present experiments that the phage T4 gene 32 protein, specifically its C-terminal domain, participates in such moderation. We have investigated DNA degradation in different gene 32 and gene 32/46 mutants under conditions that are completely restrictive for progeny production in all the mutants. Under these conditions, DNA of those gene 32 mutants in which the C-terminal domain of the protein is not synthesized or is modified is degraded to acid-soluble material. T4 gene 46 or E. coli recB mutations reduce such degradation; together they abolish it completely. By contrast, single gene 32 mutants which produce an unaltered C-terminal domain show little or no degradation of their DNA. Residual protection against nucleases is unrelated to residual primary DNA replication or to overproduction of the mutant peptides in the different gene 32 mutants."} {"id": "PMID:1255857", "title": "Process of infection with bacteriophage phi X 174 XXXVIII. Replication of phi chi 174 replicative form in vivo.", "content": "The replication of bacteriophage phi X 174 replicative-form DNA has been studied by structural analysis of pulse-labeled replicative-intermediate molecules. Such intermediates were identified by pulse-labeling with [13H]thymidine and separated into four major fractions (A, B, C, and D) in a propidium diiodide-cesium chloride buoyand density gradient. Sedimentation analysis of each of these fractions suggests the following features of phi X replicative-form DNA replication in vivo. (i) At the end of one cycle of replication, one daughter replicative form (RFII) contains a nascent plus (+) strand of the unit viral length, and the other daughter RFII contains small fragments of nascent minus (-) strand. (ii) Asymmetry is also associated with production of the first supercoiled RFI after addition of pulse label in that only the minus strand becomes radioactive. (iii) A supercoiled DNA (RFI') seems to occur in vivo. This DNA is observed at a position of greater density in a propidium diiodide-cesium chloride buoyant density gradient than normal RFI. (iv) A novel DNA component is observed, at a density greater than RFI, which releases, in alkali, a plus strand longer (1.5 to 1.7 times) than the unit viral length. These results are discussed in terms of the possible sequence of events in phi X 174 replicative-form replication in vivo.", "contents": "Process of infection with bacteriophage phi X 174 XXXVIII. Replication of phi chi 174 replicative form in vivo. The replication of bacteriophage phi X 174 replicative-form DNA has been studied by structural analysis of pulse-labeled replicative-intermediate molecules. Such intermediates were identified by pulse-labeling with [13H]thymidine and separated into four major fractions (A, B, C, and D) in a propidium diiodide-cesium chloride buoyand density gradient. Sedimentation analysis of each of these fractions suggests the following features of phi X replicative-form DNA replication in vivo. (i) At the end of one cycle of replication, one daughter replicative form (RFII) contains a nascent plus (+) strand of the unit viral length, and the other daughter RFII contains small fragments of nascent minus (-) strand. (ii) Asymmetry is also associated with production of the first supercoiled RFI after addition of pulse label in that only the minus strand becomes radioactive. (iii) A supercoiled DNA (RFI') seems to occur in vivo. This DNA is observed at a position of greater density in a propidium diiodide-cesium chloride buoyant density gradient than normal RFI. (iv) A novel DNA component is observed, at a density greater than RFI, which releases, in alkali, a plus strand longer (1.5 to 1.7 times) than the unit viral length. These results are discussed in terms of the possible sequence of events in phi X 174 replicative-form replication in vivo."} {"id": "PMID:1255858", "title": "Late events in T4 bacteriophage production. I. Late DNA replication is primarily exponential.", "content": "The possibility of a switch in the mechanism of T4 DNA replication, from an exponential-bidirectional mode at early stages to a nonexponential (rolling circle) mode at later stages of phage development, has been investigated. The conclusion that DNA replication does not involve such a change in mechanism for the majority of replicating molecules is based on the analysis of the clonal distribution of mutants specifically induced at late times after infection. The clonal distribution of mutants, induced by adding 5-bromodeoxyuridine to infected cells at a time when 100 phage equivalents of DNA had accumulated, fits the pattern predicted by exponential replication.", "contents": "Late events in T4 bacteriophage production. I. Late DNA replication is primarily exponential. The possibility of a switch in the mechanism of T4 DNA replication, from an exponential-bidirectional mode at early stages to a nonexponential (rolling circle) mode at later stages of phage development, has been investigated. The conclusion that DNA replication does not involve such a change in mechanism for the majority of replicating molecules is based on the analysis of the clonal distribution of mutants specifically induced at late times after infection. The clonal distribution of mutants, induced by adding 5-bromodeoxyuridine to infected cells at a time when 100 phage equivalents of DNA had accumulated, fits the pattern predicted by exponential replication."} {"id": "PMID:1255859", "title": "Late events in T4 bacteriophage production. II. Giant bacteriophages contain concatemers generated by recombination.", "content": "Analysis of \"giant\" phage, which package concatenated DNA into their capsids, shows that they are predominantly heterozygous. The results are compatible with the hypothesis that concatemers are generated by recombination.", "contents": "Late events in T4 bacteriophage production. II. Giant bacteriophages contain concatemers generated by recombination. Analysis of \"giant\" phage, which package concatenated DNA into their capsids, shows that they are predominantly heterozygous. The results are compatible with the hypothesis that concatemers are generated by recombination."} {"id": "PMID:1255860", "title": "Multiplication of parvovirus LuIII in a synchronized culture system. III. Replication of viral DNA.", "content": "The replication of the single-stranded DNA (ssDNA) of parvovirus LuIII was studied in synchronized HeLa cells. After infection of the cells in early S phase, synthesis of a replicative form (RF) DNA became detectable as early as 9 h postinfection, i.e., after display of the cellular helper function(s) indispensable for the replication of LuIII virus. According to digestion with nuclease S1, hybridization studies, and electron microscopy, RF DNA is a linear, double-stranded molecule comparable in length to mature ssDNA. It sedimented around 15S in neutral solution and banded at 1.714 g/ml in CsCl. Moreover, replication of LuIII DNA obviously includes a further replicative intermediate DNA which sedimented in front of RF DNA and bore single-stranded side-chains. Newly synthesized DNA disappeared from pools containing both RF DNA and replicative intermediate DNA within 5 min and reappeared in progeny virions only after 15 min. Intranuclear accumulation of significant amounts of progeny ssDNA could not be detected. It was postulated, therefore, that newly synthesized ssDNA is immediately enclosed in a stable maturation complex and resists extraction by the method of Hirt (1967).", "contents": "Multiplication of parvovirus LuIII in a synchronized culture system. III. Replication of viral DNA. The replication of the single-stranded DNA (ssDNA) of parvovirus LuIII was studied in synchronized HeLa cells. After infection of the cells in early S phase, synthesis of a replicative form (RF) DNA became detectable as early as 9 h postinfection, i.e., after display of the cellular helper function(s) indispensable for the replication of LuIII virus. According to digestion with nuclease S1, hybridization studies, and electron microscopy, RF DNA is a linear, double-stranded molecule comparable in length to mature ssDNA. It sedimented around 15S in neutral solution and banded at 1.714 g/ml in CsCl. Moreover, replication of LuIII DNA obviously includes a further replicative intermediate DNA which sedimented in front of RF DNA and bore single-stranded side-chains. Newly synthesized DNA disappeared from pools containing both RF DNA and replicative intermediate DNA within 5 min and reappeared in progeny virions only after 15 min. Intranuclear accumulation of significant amounts of progeny ssDNA could not be detected. It was postulated, therefore, that newly synthesized ssDNA is immediately enclosed in a stable maturation complex and resists extraction by the method of Hirt (1967)."} {"id": "PMID:1255861", "title": "In vivo and in vitro synthesis of adenovirus type 2 early proteins.", "content": "The synthesis of adenovirus type 2 (Ad2)-induced early polypeptides was examined in vivo and in vitro by a combination of sodium dodecyl sulfate-polyacrylamide gel electrophoresis alone and specific immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of total [35S]methionine-labeled polypeptides synthesized in vivo at 3 h postinfection allowed us to detect in infected cells at lease 13 distinct polypeptides that are either absent or less conspicuous in extracts from mock-infected cells. These Ad2-induced early polypeptides have molecular weights ranging from 72 x 10(3) to 10.5 x 10(3) and have accordingly been designated as E72K to E10.5K. Nine of the in vivo synthesized early polypeptides can be precipitated specifically from infected cell extracts by antisera with specificity against early adenovirus proteins. In vitro translation of mRNA extracted from mock-infected cells and from Ad2-infected cells was carried out in preincubated Ehrlich ascites cell extracts. All the early Ad2-induced polypeptides identified in the extracts from infected cells labeled in vivo were also detected among the polypeptides immunoprecipitated specifically from the in vitro reaction mixtures programmed by RNA extracted at 4 h postinfection from Ad2-infected cells.", "contents": "In vivo and in vitro synthesis of adenovirus type 2 early proteins. The synthesis of adenovirus type 2 (Ad2)-induced early polypeptides was examined in vivo and in vitro by a combination of sodium dodecyl sulfate-polyacrylamide gel electrophoresis alone and specific immunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Analysis of total [35S]methionine-labeled polypeptides synthesized in vivo at 3 h postinfection allowed us to detect in infected cells at lease 13 distinct polypeptides that are either absent or less conspicuous in extracts from mock-infected cells. These Ad2-induced early polypeptides have molecular weights ranging from 72 x 10(3) to 10.5 x 10(3) and have accordingly been designated as E72K to E10.5K. Nine of the in vivo synthesized early polypeptides can be precipitated specifically from infected cell extracts by antisera with specificity against early adenovirus proteins. In vitro translation of mRNA extracted from mock-infected cells and from Ad2-infected cells was carried out in preincubated Ehrlich ascites cell extracts. All the early Ad2-induced polypeptides identified in the extracts from infected cells labeled in vivo were also detected among the polypeptides immunoprecipitated specifically from the in vitro reaction mixtures programmed by RNA extracted at 4 h postinfection from Ad2-infected cells."} {"id": "PMID:1255862", "title": "Differences in RNA patterns of influenza A viruses.", "content": "Analysis of the segmented RNAs of influenza A viruses by electrophoresis on polyacrylamide urea slab gels has provided a method for sharper resolution of the number and migration rates of different segments than previously has been possible. Using this system, the RNA genome of influenza A/WSN (HON1) virus can be separated into seven to nine separate bands, depending on whether virus is obtained after high or low multiplicity of infection, and the genome of influenza A/PR/8 (HON1) virus can be resolved into eight bands, six of which migrate differently from comparable RNA bands of WSN virus. Comparision of the RNA patterns produced by influenza A/PR/8 (HON1) and A/England/42/72 (H8n2) virus also reveals major differences in migration speeds of different bands, and analysis of the RNAs of the RNAs of an HON2 recombinant virus derived from these two strains permits the identification of RNA segments which have been derived from one particular parent. By extension of these techniques, it may be possible to define which RNA segment codes for each viral protein and to analyze recombinant strains to identify which genes have been derived from each of its parents.", "contents": "Differences in RNA patterns of influenza A viruses. Analysis of the segmented RNAs of influenza A viruses by electrophoresis on polyacrylamide urea slab gels has provided a method for sharper resolution of the number and migration rates of different segments than previously has been possible. Using this system, the RNA genome of influenza A/WSN (HON1) virus can be separated into seven to nine separate bands, depending on whether virus is obtained after high or low multiplicity of infection, and the genome of influenza A/PR/8 (HON1) virus can be resolved into eight bands, six of which migrate differently from comparable RNA bands of WSN virus. Comparision of the RNA patterns produced by influenza A/PR/8 (HON1) and A/England/42/72 (H8n2) virus also reveals major differences in migration speeds of different bands, and analysis of the RNAs of the RNAs of an HON2 recombinant virus derived from these two strains permits the identification of RNA segments which have been derived from one particular parent. By extension of these techniques, it may be possible to define which RNA segment codes for each viral protein and to analyze recombinant strains to identify which genes have been derived from each of its parents."} {"id": "PMID:1255863", "title": "Demonstration of subpopulations of Dane particles.", "content": "Two populations of Dane particles were isolated from the plasma of individuals carrying hepatitis B surface antigen. These populations had densities in CsCl of 1.22 and 1.20 g/ml. Endogenous DNA polymerase activity was found to be associated only with the heavier of these two populations. Using a positive stain, electron microscopic examination of these particles suggested that the heavier the particle contained nucleic acid in its core whereas the lighter particle appeared empty. Cores isolated from Dane particles with densities of 1.22 and 1.20 g/ml banded in CsCl at densities of 1.36 and 1.30 g/ml, respectively. Endogenous DNA polymerase activity was associated only with the higher density core particles.", "contents": "Demonstration of subpopulations of Dane particles. Two populations of Dane particles were isolated from the plasma of individuals carrying hepatitis B surface antigen. These populations had densities in CsCl of 1.22 and 1.20 g/ml. Endogenous DNA polymerase activity was found to be associated only with the heavier of these two populations. Using a positive stain, electron microscopic examination of these particles suggested that the heavier the particle contained nucleic acid in its core whereas the lighter particle appeared empty. Cores isolated from Dane particles with densities of 1.22 and 1.20 g/ml banded in CsCl at densities of 1.36 and 1.30 g/ml, respectively. Endogenous DNA polymerase activity was associated only with the higher density core particles."} {"id": "PMID:1255864", "title": "Head morphologies in bacteriophage T4 head and internal protein mutant infections.", "content": "Escherichia coli infected with phage T4 mutants defective in synthesis of the three major internal proteins found in the phage head, IPI-, IPII-, IPIII-, or IP degrees (lacking all three) were examined in the electron microscope for head formation. Infection with IPI- or IPII- does not appear to induce increased aberrant head formation, whereas IPII- or IP degrees infections result in production of polyheads and viable phage. Multiple mutants of the early head formation genes 20, 21, 22, 23, 24, 31, 40 and IP degrees were constructed. Combination with IP degrees increases polyhead formation when head formation is not blocked at a more defective stage but results in a qualitative shift to lump formation in association with gene 22 mutants. Thin-sectioning studies show morphologically similar cores in amber 21 and 21am IP degrees tau particles. These morphological observations, genetic evidence for interaction between ts mutants in gene 22 and the IP mutants, and analysis of the protein composition of tau particles further support the idea that p22 and the internal proteins form an unstable assembly core necessary for an early stage of head formation (M. K. Showe and L. W. Black, 1973).", "contents": "Head morphologies in bacteriophage T4 head and internal protein mutant infections. Escherichia coli infected with phage T4 mutants defective in synthesis of the three major internal proteins found in the phage head, IPI-, IPII-, IPIII-, or IP degrees (lacking all three) were examined in the electron microscope for head formation. Infection with IPI- or IPII- does not appear to induce increased aberrant head formation, whereas IPII- or IP degrees infections result in production of polyheads and viable phage. Multiple mutants of the early head formation genes 20, 21, 22, 23, 24, 31, 40 and IP degrees were constructed. Combination with IP degrees increases polyhead formation when head formation is not blocked at a more defective stage but results in a qualitative shift to lump formation in association with gene 22 mutants. Thin-sectioning studies show morphologically similar cores in amber 21 and 21am IP degrees tau particles. These morphological observations, genetic evidence for interaction between ts mutants in gene 22 and the IP mutants, and analysis of the protein composition of tau particles further support the idea that p22 and the internal proteins form an unstable assembly core necessary for an early stage of head formation (M. K. Showe and L. W. Black, 1973)."} {"id": "PMID:1255866", "title": "Newcastle disease virus-specific RNA: poly(A)-containing and poly(A)-deficient transcripts as revealed by chromatography on poly(U)-sepharose.", "content": "Total [3H]uridine-labeled, virus-specific RNA from Newcastle disease virus-infected cells was fractionated by poly(U)-sepharose chromatography and analyzed by rate zonal gradient centrifugation. The sedimentation pattern of both eluted and nonadsorbed RNA resembled that of the total RNA. However, nonadsorbed RNA was enriched in 50S material, ant its 18S peak was broader and slightly shifted towards the top of the gradient. Poly(U-sepharose chromatography of isolated 18S RNA and 24S RNA resulted in the separation of poly(A)-containing RNA and poly(A)-deficient RNA. In the former the percentage of adenosine content represented by poly(A) sequences was estimated as 10 to 12% (for 18S RNA) or approximately 6.0% (for 24S RNA). The size of poly(A) fragments as measured by their sedimentation rate was the same for 18S and 24S RNA. Polyacrylamide gel electrophoresis of poly(A)-containing RNA revealed a characteristic pattern closely resembling the pattern of nonchromatographed 18S and 24S RNA. The pattern of poly(A)-deficient RNA was heterogenous, and for 18S RNA it shifted towards the anode. The possible origin of poly(A)-deficient transcripts is discussed.", "contents": "Newcastle disease virus-specific RNA: poly(A)-containing and poly(A)-deficient transcripts as revealed by chromatography on poly(U)-sepharose. Total [3H]uridine-labeled, virus-specific RNA from Newcastle disease virus-infected cells was fractionated by poly(U)-sepharose chromatography and analyzed by rate zonal gradient centrifugation. The sedimentation pattern of both eluted and nonadsorbed RNA resembled that of the total RNA. However, nonadsorbed RNA was enriched in 50S material, ant its 18S peak was broader and slightly shifted towards the top of the gradient. Poly(U-sepharose chromatography of isolated 18S RNA and 24S RNA resulted in the separation of poly(A)-containing RNA and poly(A)-deficient RNA. In the former the percentage of adenosine content represented by poly(A) sequences was estimated as 10 to 12% (for 18S RNA) or approximately 6.0% (for 24S RNA). The size of poly(A) fragments as measured by their sedimentation rate was the same for 18S and 24S RNA. Polyacrylamide gel electrophoresis of poly(A)-containing RNA revealed a characteristic pattern closely resembling the pattern of nonchromatographed 18S and 24S RNA. The pattern of poly(A)-deficient RNA was heterogenous, and for 18S RNA it shifted towards the anode. The possible origin of poly(A)-deficient transcripts is discussed."} {"id": "PMID:1255865", "title": "Isolation and characterization of an extremely basic protein from adenovirus type 5.", "content": "By starch-gel electrophoresis and a staining method that is highly sensitive for argininyl residues, adenovirus type 5 was found to contain two minor basic polypeptides of extreme cathodic mobility in addition to the two known core proteins. The fastest-migrating polypeptide, named mu protein, and the second fastest polypeptide are found in adenovirions and virus-infected KB cells but not in top components or in uninfected cells. The top components and infected cells contain an additional basic polypeptide, presumably P-VII, that migrates slightly slower than polypeptide VII. None of the basic polypeptides of adenovirions was electrophoretically identical to the host histone. The basic proteins of adenovirions were purified by urea phosphocellulose column chromatography and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The two minor basic core proteins, mu and another component, have similar mobilities in sodium dodecyl sulfate-polyacrylamide gels as a complex of polypeptides X-XII. After further purification on a Sephadex G-75 column, the mu protein was found to have a molecular weight of about 4,000. Amino acid analysis showed that the mu protein lacks tryptophan and 69% of the total amino acid residues are basic, that is, 54% arginine, 13% histidine, and 2% lysine. Only eight amino acids seem to contribute to make the mu polypeptide. There are 125 copies of the mu polypeptide per 1,000 copies of polypeptide VII in a virion.", "contents": "Isolation and characterization of an extremely basic protein from adenovirus type 5. By starch-gel electrophoresis and a staining method that is highly sensitive for argininyl residues, adenovirus type 5 was found to contain two minor basic polypeptides of extreme cathodic mobility in addition to the two known core proteins. The fastest-migrating polypeptide, named mu protein, and the second fastest polypeptide are found in adenovirions and virus-infected KB cells but not in top components or in uninfected cells. The top components and infected cells contain an additional basic polypeptide, presumably P-VII, that migrates slightly slower than polypeptide VII. None of the basic polypeptides of adenovirions was electrophoretically identical to the host histone. The basic proteins of adenovirions were purified by urea phosphocellulose column chromatography and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The two minor basic core proteins, mu and another component, have similar mobilities in sodium dodecyl sulfate-polyacrylamide gels as a complex of polypeptides X-XII. After further purification on a Sephadex G-75 column, the mu protein was found to have a molecular weight of about 4,000. Amino acid analysis showed that the mu protein lacks tryptophan and 69% of the total amino acid residues are basic, that is, 54% arginine, 13% histidine, and 2% lysine. Only eight amino acids seem to contribute to make the mu polypeptide. There are 125 copies of the mu polypeptide per 1,000 copies of polypeptide VII in a virion."} {"id": "PMID:1255867", "title": "Recombination between temperature-sensitive and deletion mutants of reovirus.", "content": "In standard pairwise crosses there was no detectable recombination between defective reovirus lacking the largest genomic segment and prototypes of the seven known classes of ts mutants. However, in such crosses between R2A (201) and the various prototypes frequencies of ts+ recombinants between 2.6 and 6.1% were observed, as others have found (Fields, 1971; Fields and Joklik, 1969). An infectious center assay was devised to measure recombination in this system, and it was found that all mixedly infected cells gave rise to ts+ recombinants in crosses between prototype ts mutants, but no recombination was detectable when the defective virus was crossed with three different ts mutants. The ts mutation of mutant R2A (201) was efficiently rescued when crossed with UV-inactivated wild-type virus but not when crossed with UV-inactivated defective virus. It is concluded from these various experiments that if there is any recombination between these defective reovirions and any known class of ts mutants it is too low to be measured by methods presently available. The kinetics of recombination were measured in cells mixedly infected with R2A (201) and R2B (352) mutants. At the earliest time progeny virus could be found in the cells the frequency of ts+ recombinants was 4.5%, and this frequency remained unchanged despite a subsequent 1,000-fold increase in progeny virus.", "contents": "Recombination between temperature-sensitive and deletion mutants of reovirus. In standard pairwise crosses there was no detectable recombination between defective reovirus lacking the largest genomic segment and prototypes of the seven known classes of ts mutants. However, in such crosses between R2A (201) and the various prototypes frequencies of ts+ recombinants between 2.6 and 6.1% were observed, as others have found (Fields, 1971; Fields and Joklik, 1969). An infectious center assay was devised to measure recombination in this system, and it was found that all mixedly infected cells gave rise to ts+ recombinants in crosses between prototype ts mutants, but no recombination was detectable when the defective virus was crossed with three different ts mutants. The ts mutation of mutant R2A (201) was efficiently rescued when crossed with UV-inactivated wild-type virus but not when crossed with UV-inactivated defective virus. It is concluded from these various experiments that if there is any recombination between these defective reovirions and any known class of ts mutants it is too low to be measured by methods presently available. The kinetics of recombination were measured in cells mixedly infected with R2A (201) and R2B (352) mutants. At the earliest time progeny virus could be found in the cells the frequency of ts+ recombinants was 4.5%, and this frequency remained unchanged despite a subsequent 1,000-fold increase in progeny virus."} {"id": "PMID:1255868", "title": "Isolation of the dengue virus envelope glycoprotein from membranes of infected cells by concanavalin A affinity chromatography.", "content": "The membranes isolated from type 2 dengue virus-infected BHK-21/15 cells contain three glycosylated virus-specified proteins; one corresponds to the virion envelope glycoprotein, V-3, whereas the other two are nonstructural virus-specified proteins, NV-2 and NV-3. A combination of two nonionic detergents, Nonidet P-40 and Triton X-305, solubilized greater than or equal to 80% of the membrane-bound protein and the majority of the type 2 dengue virus complement-fixing antigens. The soluble material was adsorbed by concanavalin A-Sepharose in the presence of the nonionic detergents, which were subsequently removed by washing with deoxycholate-containing buffer. Finally, the bound glycoprotein was eluted by the addition of alpha-methyl glucopyranoside. V-3 was the only virus-specified protein in the alpha-methyl glucopyranoside eluate. The V-3-containing fraction did not cross-react with antisera against other selected Flaviviruses in the complement fixation tests. The V-3 contained in the isolated fraction differed from the parent membrane-bound V-3 in two interesting, and as yet unexplained, ways: (i) it exhibited hemagglutinating activity similar to that of the infectious virus, but (ii) it did not block the action of neutralizing antibody.", "contents": "Isolation of the dengue virus envelope glycoprotein from membranes of infected cells by concanavalin A affinity chromatography. The membranes isolated from type 2 dengue virus-infected BHK-21/15 cells contain three glycosylated virus-specified proteins; one corresponds to the virion envelope glycoprotein, V-3, whereas the other two are nonstructural virus-specified proteins, NV-2 and NV-3. A combination of two nonionic detergents, Nonidet P-40 and Triton X-305, solubilized greater than or equal to 80% of the membrane-bound protein and the majority of the type 2 dengue virus complement-fixing antigens. The soluble material was adsorbed by concanavalin A-Sepharose in the presence of the nonionic detergents, which were subsequently removed by washing with deoxycholate-containing buffer. Finally, the bound glycoprotein was eluted by the addition of alpha-methyl glucopyranoside. V-3 was the only virus-specified protein in the alpha-methyl glucopyranoside eluate. The V-3-containing fraction did not cross-react with antisera against other selected Flaviviruses in the complement fixation tests. The V-3 contained in the isolated fraction differed from the parent membrane-bound V-3 in two interesting, and as yet unexplained, ways: (i) it exhibited hemagglutinating activity similar to that of the infectious virus, but (ii) it did not block the action of neutralizing antibody."} {"id": "PMID:1255869", "title": "Viral transcription in KB cells infected by temperature-sensitive \"early\" mutants of adenovirus type 5.", "content": "RNA:DNA hybridization was used to study the synthesis of viral RNA in two DNA-minus, temperature-sensitive mutants of type 5 adenovirus (H5ts125 and H5ts149) belonging to two different, non-overlapping complementation groups. Hybridization competition analysis showed that both mutants transcribed all early gene sequences at the restrictive temperature (41 C). In mutant-infected cells at 41 C, the rate of viral transcription was similar to the rate of early RNA synthesis in wild-type virus infection and was dependent on the multiplicity of infection; little or no late transcription was detected. The shutoff of class I early RNA transcription was shown to be a late function during wild-type virus infection and did not occur at 41 C in mutant-infected cells. When mutant-infected cells were incubated at the permissive temperature (32 C) for 25 h and then shifted to 41 C, the rate of viral DNA synthesis decreased rapidly for H5ts125 and slowly for H5ts149. However, the rate of viral transcription remained unchanged in H5ts125-infected cells for at least 3 h after the temperature shift; although the synthesis of viral DNA had stopped by this time, the synthesis of late viral RNA sequences continued.", "contents": "Viral transcription in KB cells infected by temperature-sensitive \"early\" mutants of adenovirus type 5. RNA:DNA hybridization was used to study the synthesis of viral RNA in two DNA-minus, temperature-sensitive mutants of type 5 adenovirus (H5ts125 and H5ts149) belonging to two different, non-overlapping complementation groups. Hybridization competition analysis showed that both mutants transcribed all early gene sequences at the restrictive temperature (41 C). In mutant-infected cells at 41 C, the rate of viral transcription was similar to the rate of early RNA synthesis in wild-type virus infection and was dependent on the multiplicity of infection; little or no late transcription was detected. The shutoff of class I early RNA transcription was shown to be a late function during wild-type virus infection and did not occur at 41 C in mutant-infected cells. When mutant-infected cells were incubated at the permissive temperature (32 C) for 25 h and then shifted to 41 C, the rate of viral DNA synthesis decreased rapidly for H5ts125 and slowly for H5ts149. However, the rate of viral transcription remained unchanged in H5ts125-infected cells for at least 3 h after the temperature shift; although the synthesis of viral DNA had stopped by this time, the synthesis of late viral RNA sequences continued."} {"id": "PMID:1255870", "title": "Introduction of interrupted secondary structure in supercoiled DNA as a function of superhelix density: consideration of hairpin structures in superhelical DNA.", "content": "PM2 DNA was prepared with different superhelical densities (sigma) in order to examine the relationship betweenn supercoiling and the occurrence of a region(s) of unpaired bases in this DNA. A previous study showed that CH3HgOH reacts with native superhelical PM2 DNA more rapidly than the nicked form II. This evaluation of binding, monitored through the change of sedimentation velocity, was repeated on PM2 DNA I with different superhelical densities. Early binding is detected by an increase in sedimentation velocity and occurs with molecules with sigma' values betwee -0.025 and -0.037. The conversion of form I to form II with the single-strand-specific endonuclease from Neurospora crassa also occurs above a sigma value of -0.025. This data strongly supports the view that supercoiling produces interrupted secondary structure. The question whether the interrupted regions remain single stranded in character or form small intrastrand hairpin regions is considered by examining which model best fits the CH3HgOH- induced sedimentation velocity changes and the standard sedimentation velocity versus the superhelical density curve for the in vitro made DNAs. The hairpin model offers the most satisfactory explanations for all the results of this and previous studies.", "contents": "Introduction of interrupted secondary structure in supercoiled DNA as a function of superhelix density: consideration of hairpin structures in superhelical DNA. PM2 DNA was prepared with different superhelical densities (sigma) in order to examine the relationship betweenn supercoiling and the occurrence of a region(s) of unpaired bases in this DNA. A previous study showed that CH3HgOH reacts with native superhelical PM2 DNA more rapidly than the nicked form II. This evaluation of binding, monitored through the change of sedimentation velocity, was repeated on PM2 DNA I with different superhelical densities. Early binding is detected by an increase in sedimentation velocity and occurs with molecules with sigma' values betwee -0.025 and -0.037. The conversion of form I to form II with the single-strand-specific endonuclease from Neurospora crassa also occurs above a sigma value of -0.025. This data strongly supports the view that supercoiling produces interrupted secondary structure. The question whether the interrupted regions remain single stranded in character or form small intrastrand hairpin regions is considered by examining which model best fits the CH3HgOH- induced sedimentation velocity changes and the standard sedimentation velocity versus the superhelical density curve for the in vitro made DNAs. The hairpin model offers the most satisfactory explanations for all the results of this and previous studies."} {"id": "PMID:1255871", "title": "Process of infection with bacteriophage phi chi 174. XL. Viral DNA replication of phi chi 174 mutants blocked in progeny single-stranded DNA synthesis.", "content": "Mutation in several different cistrons of bacteriophage phi chi 174 blocks net progeny single-stranded DNA synthesis at the late period of infection (15). For the study of the functions of these cistrons in single-stranded DNA synthesis, asymmetric replication of replicative form DNA was examined at the late period of infection with amber mutants of these cistrons. While the normal, rapid process of asymmetric single-stranded viral DNA synthesis is blocked at the late period of these mutant infections, an asymmetric synthesis of the viral strand of replicative-form DNA is observed in this period, though at a reduced level, together with degradation of prelabeled viral strand. Some intermediate replicative-form molecules were also detected. Asymmetric synthesis of the viral strand of replicative-form DNA at the late period of phi chi infection is completely inhibited in the presence of a low concentration (35mug/ml) of chloramphenicol (which also blocks net single-stranded viral DNA synthesis). These results are discussed in terms of the possible role of the specific viral proteins for normal single-stranded DNA synthesis.", "contents": "Process of infection with bacteriophage phi chi 174. XL. Viral DNA replication of phi chi 174 mutants blocked in progeny single-stranded DNA synthesis. Mutation in several different cistrons of bacteriophage phi chi 174 blocks net progeny single-stranded DNA synthesis at the late period of infection (15). For the study of the functions of these cistrons in single-stranded DNA synthesis, asymmetric replication of replicative form DNA was examined at the late period of infection with amber mutants of these cistrons. While the normal, rapid process of asymmetric single-stranded viral DNA synthesis is blocked at the late period of these mutant infections, an asymmetric synthesis of the viral strand of replicative-form DNA is observed in this period, though at a reduced level, together with degradation of prelabeled viral strand. Some intermediate replicative-form molecules were also detected. Asymmetric synthesis of the viral strand of replicative-form DNA at the late period of phi chi infection is completely inhibited in the presence of a low concentration (35mug/ml) of chloramphenicol (which also blocks net single-stranded viral DNA synthesis). These results are discussed in terms of the possible role of the specific viral proteins for normal single-stranded DNA synthesis."} {"id": "PMID:1255872", "title": "Multiple origins and circular structures in replicating T5 bacteriophage DNA.", "content": "Replicating T5 phage DNA was gently isolated using NaI density gradient centrifugation and examined by electron microscopy. At the beginning of phage DNA synthesis, linear unit-length T5 DNA molecules containing from one to four replicating \"eye-loops\" were consistently observed. Replication in these molecules was found to proceed bidirectionally from multiple, internal origins. A primary origin of replication is located near the center of the T5 genome, which does not coincide with the location of any of the nicks (single-strand breaks) found in mature T5 DNA. The initiation of replication at the various origins within an individual molecule does not appear to follow any definite temporal sequence. At later times in the infection, we have observed a significant number of circular T5 DNA molecules-both replicating and nonreplicating-whose average circumference is approximately the length of mature T5 DNA minus the terminal redundancy. The replicating circular molecules appear to be either in a theta configuration, a sigma configuration with the tails all being less than the length of the circle, or a combination of theta and sigma forms.", "contents": "Multiple origins and circular structures in replicating T5 bacteriophage DNA. Replicating T5 phage DNA was gently isolated using NaI density gradient centrifugation and examined by electron microscopy. At the beginning of phage DNA synthesis, linear unit-length T5 DNA molecules containing from one to four replicating \"eye-loops\" were consistently observed. Replication in these molecules was found to proceed bidirectionally from multiple, internal origins. A primary origin of replication is located near the center of the T5 genome, which does not coincide with the location of any of the nicks (single-strand breaks) found in mature T5 DNA. The initiation of replication at the various origins within an individual molecule does not appear to follow any definite temporal sequence. At later times in the infection, we have observed a significant number of circular T5 DNA molecules-both replicating and nonreplicating-whose average circumference is approximately the length of mature T5 DNA minus the terminal redundancy. The replicating circular molecules appear to be either in a theta configuration, a sigma configuration with the tails all being less than the length of the circle, or a combination of theta and sigma forms."} {"id": "PMID:1255873", "title": "Bidirectional replication of adenovirus type 2 DNA.", "content": "After short periods of labeling with [3H]thymidine, recently completed adenovirus DNA molecules were isolated and cleaved with restriction endonucleases. The strands (heavy and light) of most of the restriction endonuclease fragments were separated. The pattern of labeling clearly shows an asymmetry of radioactivity on the isolated strands of each restriction endonuclease piece. The data is consistent with replication proceeding in the 5' to 3' direction on each strand. Thus, there is an initiation point placed at or near each end of the molecule.", "contents": "Bidirectional replication of adenovirus type 2 DNA. After short periods of labeling with [3H]thymidine, recently completed adenovirus DNA molecules were isolated and cleaved with restriction endonucleases. The strands (heavy and light) of most of the restriction endonuclease fragments were separated. The pattern of labeling clearly shows an asymmetry of radioactivity on the isolated strands of each restriction endonuclease piece. The data is consistent with replication proceeding in the 5' to 3' direction on each strand. Thus, there is an initiation point placed at or near each end of the molecule."} {"id": "PMID:1255874", "title": "Comparative electrophoresis of the 18-22S RNAs of Newcastle disease virus.", "content": "Between 80 and 90% of the 18-22S Newcastle disease virus intracellular RNA molecules contain poly(A) sequences. Electrophoresis of the 18S RNA in formamide-polyacrylamide gels resolves five species resolved by electrophoresis in aqueous gels. Thus, these five RNA species are probably unique size classes of RNA and not different conformations of the same RNAs. They are of sufficient size to code for the five smaller Newcastle disease virus proteins, and their combined molecular weights represent 60% of the viral genome-a value identical to that obtained by annealing 18-22S RNA with genome RNA. Formamide or heat treatment of the 22S RNA converts most of it into species with migration rates similar to those of the 18S species. Thus, the 22S RNA may not contain unique RNA species.", "contents": "Comparative electrophoresis of the 18-22S RNAs of Newcastle disease virus. Between 80 and 90% of the 18-22S Newcastle disease virus intracellular RNA molecules contain poly(A) sequences. Electrophoresis of the 18S RNA in formamide-polyacrylamide gels resolves five species resolved by electrophoresis in aqueous gels. Thus, these five RNA species are probably unique size classes of RNA and not different conformations of the same RNAs. They are of sufficient size to code for the five smaller Newcastle disease virus proteins, and their combined molecular weights represent 60% of the viral genome-a value identical to that obtained by annealing 18-22S RNA with genome RNA. Formamide or heat treatment of the 22S RNA converts most of it into species with migration rates similar to those of the 18S species. Thus, the 22S RNA may not contain unique RNA species."} {"id": "PMID:1255876", "title": "Transcriptase activity and genome composition of defective influenza virus.", "content": "Eight genome RNA segments are present in both normal and von Magnustype influenza virus preparations and all species are transcribed by the virion-associated polymerase. Although the RNA polymerase activity and the amount of the three largest RNA segments are reduced in defective influenza virus preparations, these reductions do not appear to be great enough to account for the much greater loss of infectivity.", "contents": "Transcriptase activity and genome composition of defective influenza virus. Eight genome RNA segments are present in both normal and von Magnustype influenza virus preparations and all species are transcribed by the virion-associated polymerase. Although the RNA polymerase activity and the amount of the three largest RNA segments are reduced in defective influenza virus preparations, these reductions do not appear to be great enough to account for the much greater loss of infectivity."} {"id": "PMID:1255875", "title": "Proteins solubilized from frog virus 3 particles: effect on transcription.", "content": "The treatment of KB cells with viral proteins solubilized from frog virus 3 particles (SVE) induced a rapid shutoff of host RNA synthesis. The RNA polymerase activities of SVE-treated cells were drastically depressed, corresonding, at least for RNA polymerase B, to a decrease in the number of enzyme molecules. In vitro, SVE had no direct effect on RNA polymerases but was capable of binding with calf thymus DNA to form an SVE-DNA complex modifying the template capacity. The effect of SVE on a transcription system consisting of cell lysates would suggest that cytoplasmic factors are necessary for expression of the inhibitory capacity of SVE.", "contents": "Proteins solubilized from frog virus 3 particles: effect on transcription. The treatment of KB cells with viral proteins solubilized from frog virus 3 particles (SVE) induced a rapid shutoff of host RNA synthesis. The RNA polymerase activities of SVE-treated cells were drastically depressed, corresonding, at least for RNA polymerase B, to a decrease in the number of enzyme molecules. In vitro, SVE had no direct effect on RNA polymerases but was capable of binding with calf thymus DNA to form an SVE-DNA complex modifying the template capacity. The effect of SVE on a transcription system consisting of cell lysates would suggest that cytoplasmic factors are necessary for expression of the inhibitory capacity of SVE."} {"id": "PMID:1255877", "title": "Regulated transcription of the genomes of defective virions and temperature-sensitive mutants of reovirus.", "content": "Defective reovirus, which lacks the largest (L1) of the 10 double-stranded (ds) RNA genomic segments, attaches to L cells and is uncoated in the same way as reovirus. The defective genome does not replicate in the cells, but it is transcribed. During the first 5 h after infection, three of the genomic segments, M3, S3, and S4, are more frequently transcribed than the remaining six segments. During the succeeding 5 h, there is a transition to a situation in which all nine segments are transcribed at the same relative frequencies. Since the class C ts mutation has been allocated to the L1 segment (Spandidos and Graham, 1975) the transcription of the C mutant genome was investigated in cells infected with it at the nonpermissive temperature, at which the parental genome does not replicate. Genomic segments L1, M3, S3, and S4 are predominantly transcribed at early times, and later all 10 segments are transcribed with the same relative frequencies. Transcription of the defective viral genome and the C mutant genome is therefore regulated in the same way as previously found for wild-type virus (Nonoyama, Millward, and Graham, 1974), and the regulation is independent of genome replication. Apparently the L1 segment function is involved in dsRNA synthesis but not in regulating the early to late transcription. It is suggested that a cellular repressor may be involved in this regulation and that derepression might be effected by one of the early viral gene products. Virion transcriptase activity was studied in vitro with cores prepared by chymotrypsin digestion of purified defective and standard virions. For both genomes the relative frequencies of transcription of the dsRNA segments are inversely proportional to their molecular weights. These results can be accounted for in a model that postulates each segment to be transcribed independently of the other. The same model with certain restrictions can describe the in vivo transcription of the viral genome.", "contents": "Regulated transcription of the genomes of defective virions and temperature-sensitive mutants of reovirus. Defective reovirus, which lacks the largest (L1) of the 10 double-stranded (ds) RNA genomic segments, attaches to L cells and is uncoated in the same way as reovirus. The defective genome does not replicate in the cells, but it is transcribed. During the first 5 h after infection, three of the genomic segments, M3, S3, and S4, are more frequently transcribed than the remaining six segments. During the succeeding 5 h, there is a transition to a situation in which all nine segments are transcribed at the same relative frequencies. Since the class C ts mutation has been allocated to the L1 segment (Spandidos and Graham, 1975) the transcription of the C mutant genome was investigated in cells infected with it at the nonpermissive temperature, at which the parental genome does not replicate. Genomic segments L1, M3, S3, and S4 are predominantly transcribed at early times, and later all 10 segments are transcribed with the same relative frequencies. Transcription of the defective viral genome and the C mutant genome is therefore regulated in the same way as previously found for wild-type virus (Nonoyama, Millward, and Graham, 1974), and the regulation is independent of genome replication. Apparently the L1 segment function is involved in dsRNA synthesis but not in regulating the early to late transcription. It is suggested that a cellular repressor may be involved in this regulation and that derepression might be effected by one of the early viral gene products. Virion transcriptase activity was studied in vitro with cores prepared by chymotrypsin digestion of purified defective and standard virions. For both genomes the relative frequencies of transcription of the dsRNA segments are inversely proportional to their molecular weights. These results can be accounted for in a model that postulates each segment to be transcribed independently of the other. The same model with certain restrictions can describe the in vivo transcription of the viral genome."} {"id": "PMID:1255878", "title": "Functional half-lives of bacteriophage m13 gene 5 and gene 8 messages.", "content": "The half-lives of the M13 gene 5 and gene 8 messages were determined by measuring the decay in the rate of synthesis of the gene 5 and gene 8 proteins after inhibition of new RNA chain initiations with rifampin. The gene 5 and gene 8 messages decay with half-lives of approximately 2.5 and 5 min, respectively. We found no evidence of a functional M13 message with a half-life as long as that reported for hybridizable mRNA.", "contents": "Functional half-lives of bacteriophage m13 gene 5 and gene 8 messages. The half-lives of the M13 gene 5 and gene 8 messages were determined by measuring the decay in the rate of synthesis of the gene 5 and gene 8 proteins after inhibition of new RNA chain initiations with rifampin. The gene 5 and gene 8 messages decay with half-lives of approximately 2.5 and 5 min, respectively. We found no evidence of a functional M13 message with a half-life as long as that reported for hybridizable mRNA."} {"id": "PMID:1255880", "title": "Traumatic renal artery occlusion: 21 cases.", "content": "Sixteen cases of unilateral and 5 cases of bilateral traumatic renal artery occlusion caused by avulsion or thrombosis are presented. The injury typically follows automobile-pedestrian accidents to young male subjects. Associated extrarenal injuries are usual but non-pedicle renal injury is infrequent. Suspicion of the unilateral injury depends upon recognition of absence of visible excretion at urography. The clue to bilateral occlusion is anuria. Diagnosis is confirmed by urgent arteriography. Hematuria was absent in 24 per cent and the injury was missed at laparotomy in 29 per cent of the initial explorations. Renal function was salvaged by arterial reconstruction in 2 cases, 12 hours and 5 months after injury respectively. Hypertension developed in 50 per cent of the cases and was generally mild.", "contents": "Traumatic renal artery occlusion: 21 cases. Sixteen cases of unilateral and 5 cases of bilateral traumatic renal artery occlusion caused by avulsion or thrombosis are presented. The injury typically follows automobile-pedestrian accidents to young male subjects. Associated extrarenal injuries are usual but non-pedicle renal injury is infrequent. Suspicion of the unilateral injury depends upon recognition of absence of visible excretion at urography. The clue to bilateral occlusion is anuria. Diagnosis is confirmed by urgent arteriography. Hematuria was absent in 24 per cent and the injury was missed at laparotomy in 29 per cent of the initial explorations. Renal function was salvaged by arterial reconstruction in 2 cases, 12 hours and 5 months after injury respectively. Hypertension developed in 50 per cent of the cases and was generally mild."} {"id": "PMID:1255881", "title": "Cell-mediated immunity in renal cell carcinoma-preliminary report.", "content": "The microcytotoxicity test was used in 8 cases post-nephrectomy for renal cell carcinoma to stage the disease clinically and to evaluate immunologically. Half of the patients had stage IV disease and half were believed to be cured clinically. Cell-mediated immunity and serum blocking factors were found in all patients with known metastases. However, cellular immunity was not found in 3 of the 4 remaining patients and serum blocking factors were also not noted in the 2 clinically cured patients who were tested. These findings are compatible with the facts that cell-mediated immunity and serum blocking factors are found when there is a grossly discernible antigenic source, that serum blocking factors are lost in patients who are clinically free of tumor and that in some patients who are clinically cured with a possible total loss of antigenic presence there is a disappearance of significant cell-mediated immunity.", "contents": "Cell-mediated immunity in renal cell carcinoma-preliminary report. The microcytotoxicity test was used in 8 cases post-nephrectomy for renal cell carcinoma to stage the disease clinically and to evaluate immunologically. Half of the patients had stage IV disease and half were believed to be cured clinically. Cell-mediated immunity and serum blocking factors were found in all patients with known metastases. However, cellular immunity was not found in 3 of the 4 remaining patients and serum blocking factors were also not noted in the 2 clinically cured patients who were tested. These findings are compatible with the facts that cell-mediated immunity and serum blocking factors are found when there is a grossly discernible antigenic source, that serum blocking factors are lost in patients who are clinically free of tumor and that in some patients who are clinically cured with a possible total loss of antigenic presence there is a disappearance of significant cell-mediated immunity."} {"id": "PMID:1255882", "title": "In vitro assessment of cell-mediated immunity in patients with renal cell carcinoma.", "content": "We evaluated 25 patients with renal cell carcinoma for cell-mediated immunity using the microtoxicity assay. Normal controls frequently exhibited significant cell inhibition. The mean percentage cell inhibition in patients after nephrectomy was significantly higher than in patients before nephrectomy and significantly higher than normal male subjects. No other correlation was found with respect to the stage of the disease. The incidence of significant autoblocking activity was noted more commonly in patients after nephrectomy than in patients before nephrectomy.", "contents": "In vitro assessment of cell-mediated immunity in patients with renal cell carcinoma. We evaluated 25 patients with renal cell carcinoma for cell-mediated immunity using the microtoxicity assay. Normal controls frequently exhibited significant cell inhibition. The mean percentage cell inhibition in patients after nephrectomy was significantly higher than in patients before nephrectomy and significantly higher than normal male subjects. No other correlation was found with respect to the stage of the disease. The incidence of significant autoblocking activity was noted more commonly in patients after nephrectomy than in patients before nephrectomy."} {"id": "PMID:1255883", "title": "Immune cytolysis of human renal carcinoma mediated by xenogeneic immune ribonucleic acid.", "content": "With a microcytotoxicity assay it was shown that normal, non-immune human lymphocytes were converted to effector cells specifically cytotoxic to human renal carcinoma cells after incubation with xenogeneic immune ribonucleic acids. The ribonucleic acid was extracted from the lymphoid tissues of sheep that had been immunized with human renal carcinoma tissue. Lymphocytes incubated without ribonucleic acid from or with ribonucleic acid sheep immunized with Freund's adjuvant alone did not increase cytotoxicity. Immunotherapy with immune ribonucleic acid increased cytotoxic activity of lymphocytes from a patient with metastatic renal carcinoma. The microcytotoxicity assay may be a useful method to assessing the cellular immune response in patients receiving immunotherapy and seems to correlate with their clinical course.", "contents": "Immune cytolysis of human renal carcinoma mediated by xenogeneic immune ribonucleic acid. With a microcytotoxicity assay it was shown that normal, non-immune human lymphocytes were converted to effector cells specifically cytotoxic to human renal carcinoma cells after incubation with xenogeneic immune ribonucleic acids. The ribonucleic acid was extracted from the lymphoid tissues of sheep that had been immunized with human renal carcinoma tissue. Lymphocytes incubated without ribonucleic acid from or with ribonucleic acid sheep immunized with Freund's adjuvant alone did not increase cytotoxicity. Immunotherapy with immune ribonucleic acid increased cytotoxic activity of lymphocytes from a patient with metastatic renal carcinoma. The microcytotoxicity assay may be a useful method to assessing the cellular immune response in patients receiving immunotherapy and seems to correlate with their clinical course."} {"id": "PMID:1255884", "title": "The interaction of host immunocompetence and tumor aggressiveness in superficial bladder carcinoma.", "content": "The results of our studies suggest that in the natural history of bladder cancer intrinsic tumor aggressiveness as measured by loss of normal antigenic activity may be more relevant than intact host defenses as measured by an intact cell-mediated immune response. Our contention that tumor aggressiveness may be the more important variable fits in with the occasional success in cancer patients treated with chemotherapeutic agents that act by altering the genetic material of rapidly dividing tumor cells. Our data suggest that therapy directed at bolstering the host's immune system may not be as effective as therapy directed against molecular events within the cancer cells themselves. Unfortunately, presently available non-surgical modalities do not discriminate between aggressor (tumor) and defender (lymphocyte) cells.", "contents": "The interaction of host immunocompetence and tumor aggressiveness in superficial bladder carcinoma. The results of our studies suggest that in the natural history of bladder cancer intrinsic tumor aggressiveness as measured by loss of normal antigenic activity may be more relevant than intact host defenses as measured by an intact cell-mediated immune response. Our contention that tumor aggressiveness may be the more important variable fits in with the occasional success in cancer patients treated with chemotherapeutic agents that act by altering the genetic material of rapidly dividing tumor cells. Our data suggest that therapy directed at bolstering the host's immune system may not be as effective as therapy directed against molecular events within the cancer cells themselves. Unfortunately, presently available non-surgical modalities do not discriminate between aggressor (tumor) and defender (lymphocyte) cells."} {"id": "PMID:1255885", "title": "Prognostic significance of regional lymph node histology in cancer of the bladder.", "content": "The regional lymph nodes from 47 patients with carcinoma of the bladder who had undergone radical cystectomy and bilateral pelvic lymphadenectomy were classified into 3 histologic patterns that correlated with immunologic function. Lymph nodes were designated as stimulated if they exhibited prominent germinal centers (B cell proliferation) and expansion of the deep cortex (T cell proliferation), depleted if they appeared markedly hypocellular and fibrotic, and unstimulated if they resembled a normal resting lymph node. Correlation of the histologic pattern with the extent of disease revealed that patients whose nodes appeared stimulated had fewer metastases (p less than 0.05) than those with either unstimulated or unstimulated combined with a depleted pattern. A markedly improved 5-year survival rate was seen in patients with a stimulated pattern (p less than 0.0001) compared to those patients who exhibited a depleted and/or unstimulated lymph node pattern. The survival advantage related to the stimulated pattern was observed primarily among patients with advanced disease. It is suggested that stimulated nodes reflect proliferation of T and B lymphocytes engaged in cell-mediated and humoral immune responses to the bladder tumor and that this favorably influenced survival in those patients. Patients whose lymph nodes showed a depleted pattern fared poorly despite the extent of the disease and those with an unstimulated pattern were intermediate in survival. A depleted pattern may represent a state of local immune paralysis, exhaustion of the draining lymph nodes as a result of exposure to excess tumor-derived products such as antigen or toxic substances or simply an atrophic node incapable of response. In the absence of a local immune response such patients might be expected to do poorly. These results suggest that morphologic evaluation of the lymph nodes regional to bladder cancer may provide a clue to their immunologic function and a more accurate guide to prognosis of patients with this neoplasm.", "contents": "Prognostic significance of regional lymph node histology in cancer of the bladder. The regional lymph nodes from 47 patients with carcinoma of the bladder who had undergone radical cystectomy and bilateral pelvic lymphadenectomy were classified into 3 histologic patterns that correlated with immunologic function. Lymph nodes were designated as stimulated if they exhibited prominent germinal centers (B cell proliferation) and expansion of the deep cortex (T cell proliferation), depleted if they appeared markedly hypocellular and fibrotic, and unstimulated if they resembled a normal resting lymph node. Correlation of the histologic pattern with the extent of disease revealed that patients whose nodes appeared stimulated had fewer metastases (p less than 0.05) than those with either unstimulated or unstimulated combined with a depleted pattern. A markedly improved 5-year survival rate was seen in patients with a stimulated pattern (p less than 0.0001) compared to those patients who exhibited a depleted and/or unstimulated lymph node pattern. The survival advantage related to the stimulated pattern was observed primarily among patients with advanced disease. It is suggested that stimulated nodes reflect proliferation of T and B lymphocytes engaged in cell-mediated and humoral immune responses to the bladder tumor and that this favorably influenced survival in those patients. Patients whose lymph nodes showed a depleted pattern fared poorly despite the extent of the disease and those with an unstimulated pattern were intermediate in survival. A depleted pattern may represent a state of local immune paralysis, exhaustion of the draining lymph nodes as a result of exposure to excess tumor-derived products such as antigen or toxic substances or simply an atrophic node incapable of response. In the absence of a local immune response such patients might be expected to do poorly. These results suggest that morphologic evaluation of the lymph nodes regional to bladder cancer may provide a clue to their immunologic function and a more accurate guide to prognosis of patients with this neoplasm."} {"id": "PMID:1255886", "title": "Male incontinence: relationship of physiology to surgery.", "content": "After prostatectomy it is the passive continence mechanism that maintains continence. Since this mechanism is less effective when the structures are not in the normal elevated position, perineal continence operations are probably successful in proportion to the mobility of the sub-prostatic structures and the ability to keep them elevated.", "contents": "Male incontinence: relationship of physiology to surgery. After prostatectomy it is the passive continence mechanism that maintains continence. Since this mechanism is less effective when the structures are not in the normal elevated position, perineal continence operations are probably successful in proportion to the mobility of the sub-prostatic structures and the ability to keep them elevated."} {"id": "PMID:1255887", "title": "Experience with the Small-Carrion penile prosthesis.", "content": "The Small-Carrion prosthesis has been implanted successfully in 14 of 15 patients. These prostheses are implanted through a dorsal midline penile incision which simplifies the procedure. The perineal approach is preferred for keloid formers and paraplegics who will use a condom catheter. Operative failure may be decreased by paying particular attention to the size of prosthesis implanted and the positioning of its distal tip.", "contents": "Experience with the Small-Carrion penile prosthesis. The Small-Carrion prosthesis has been implanted successfully in 14 of 15 patients. These prostheses are implanted through a dorsal midline penile incision which simplifies the procedure. The perineal approach is preferred for keloid formers and paraplegics who will use a condom catheter. Operative failure may be decreased by paying particular attention to the size of prosthesis implanted and the positioning of its distal tip."} {"id": "PMID:1255888", "title": "Experience with the Small-Carrion penile prosthesis in the treatment of organic impotence.", "content": "Since certain animals are endowed with an os penis the concept of using penile implants was a natural development. Herein we report on our experience with the Small-Carrion penile prosthesis in 23 patients. The surgical technique is described as well as several examples of postoperative results. The major complication encountered was infection. All patients were able to accomplish coitus without significant difficulty. Proper patient selection and the attitude of the sexual partner constitute the major factors in the ultimate success or failure of the procedure.", "contents": "Experience with the Small-Carrion penile prosthesis in the treatment of organic impotence. Since certain animals are endowed with an os penis the concept of using penile implants was a natural development. Herein we report on our experience with the Small-Carrion penile prosthesis in 23 patients. The surgical technique is described as well as several examples of postoperative results. The major complication encountered was infection. All patients were able to accomplish coitus without significant difficulty. Proper patient selection and the attitude of the sexual partner constitute the major factors in the ultimate success or failure of the procedure."} {"id": "PMID:1255889", "title": "A study of meiotic preparation of human spermatocytes and their relationship to infertility.", "content": "Although our experience is based on a small series of 50 cases we believe that several points can be made. Meiotic preparations can be performed in any competent cytogenetic laboratory. These preparations appear to yield more specific information as to the site of arrest and may be more reliable than the static testicular biopsy to appraise the true status of spermatogenesis. With these facts in mind a more accurate prognosis and therapeutic regimen can be realized.", "contents": "A study of meiotic preparation of human spermatocytes and their relationship to infertility. Although our experience is based on a small series of 50 cases we believe that several points can be made. Meiotic preparations can be performed in any competent cytogenetic laboratory. These preparations appear to yield more specific information as to the site of arrest and may be more reliable than the static testicular biopsy to appraise the true status of spermatogenesis. With these facts in mind a more accurate prognosis and therapeutic regimen can be realized."} {"id": "PMID:1255890", "title": "Renal abscess: a changing concept.", "content": "Gram-negative organisms are not the most prevalent bacterial species found in renal abscesses. We postulate an ascending pathway for establishment of gram-negative abscesses. Voiding cystourethrography should be used in search of reflux. Surgical treatment remains the standard but early diagnosis may increase the effectiveness of parenteral antibiotics as definitive therapy.", "contents": "Renal abscess: a changing concept. Gram-negative organisms are not the most prevalent bacterial species found in renal abscesses. We postulate an ascending pathway for establishment of gram-negative abscesses. Voiding cystourethrography should be used in search of reflux. Surgical treatment remains the standard but early diagnosis may increase the effectiveness of parenteral antibiotics as definitive therapy."} {"id": "PMID:1255891", "title": "Excretory urographic demonstration of ureteral displacement by sigmoid fecal impaction simulating retroperitoneal tumor.", "content": "Two cases of curvilinear lateral ureteral displacement in children with abdominal masses are reported. The masses proved to be sigmoid fecal impactions. This possibility must be considered before embarking on radiographic or surgical evaluation of possible retroperitoneal neoplasm.", "contents": "Excretory urographic demonstration of ureteral displacement by sigmoid fecal impaction simulating retroperitoneal tumor. Two cases of curvilinear lateral ureteral displacement in children with abdominal masses are reported. The masses proved to be sigmoid fecal impactions. This possibility must be considered before embarking on radiographic or surgical evaluation of possible retroperitoneal neoplasm."} {"id": "PMID:1255892", "title": "Intrarenal reflux and renal damage.", "content": "The retrograde flow of dye from the calices into the collecting tubules (intrarenal reflux) seen during cystrography in children and its effect on the kidneys were evaluated. A retrospective analysis was made of 175 patients with excretory urograms revealing cortical atrophy. Of these patients 68 per cent had cystograms revealing vesicoureteral reflux. Intrarenal reflux was seen in 8 patients less than 6 years old, an incidence of 13.5 per cent in that age group. There was a high correlation, 7 of 8 or 87.5 per cent, between the areas of intrarenal reflux, and associated renal cortical atrophy and calicectasis. Intrarenal reflux provides a pathway by which bacteria and hydrostatic pressure may produce injury to the renal parenchyma. The presence of intrarenal reflux is an absolute indication for ureteroneocystostomy.", "contents": "Intrarenal reflux and renal damage. The retrograde flow of dye from the calices into the collecting tubules (intrarenal reflux) seen during cystrography in children and its effect on the kidneys were evaluated. A retrospective analysis was made of 175 patients with excretory urograms revealing cortical atrophy. Of these patients 68 per cent had cystograms revealing vesicoureteral reflux. Intrarenal reflux was seen in 8 patients less than 6 years old, an incidence of 13.5 per cent in that age group. There was a high correlation, 7 of 8 or 87.5 per cent, between the areas of intrarenal reflux, and associated renal cortical atrophy and calicectasis. Intrarenal reflux provides a pathway by which bacteria and hydrostatic pressure may produce injury to the renal parenchyma. The presence of intrarenal reflux is an absolute indication for ureteroneocystostomy."} {"id": "PMID:1255893", "title": "Urinary diversion for neurogenic bladder in children.", "content": "The fate of the upper urinary tracts after urinary diversion will determine its place in the management of neurogenic and congenital bladder lesions. In this study there was an over-all 13 per cent deterioration rate in the upper tracts after ileac and colonic diversions. The status of the upper tracts at the time of diversion was believed to be a significant factor in the prognosis.", "contents": "Urinary diversion for neurogenic bladder in children. The fate of the upper urinary tracts after urinary diversion will determine its place in the management of neurogenic and congenital bladder lesions. In this study there was an over-all 13 per cent deterioration rate in the upper tracts after ileac and colonic diversions. The status of the upper tracts at the time of diversion was believed to be a significant factor in the prognosis."} {"id": "PMID:1255894", "title": "Scrotal swelling in the Sch\u00f6nlein-Henoch syndrome.", "content": "Testicular and scrotal hemorrhage is uncommon in the Sch\u00f6nlein-Henoch syndrome. The diagnosis of testicular torsion is difficult to make when it is complicated by vasculitis of the testis. Since both conditions can occur simultaneously, torsion of the testis must be considered and surgical exploration performed whenever acute testicular pain and swelling occur during the course of the Sch\u00f6nlein-Henoch syndrome. Two patients with this syndrome as well as scrotal and testicular involvement are described.", "contents": "Scrotal swelling in the Sch\u00f6nlein-Henoch syndrome. Testicular and scrotal hemorrhage is uncommon in the Sch\u00f6nlein-Henoch syndrome. The diagnosis of testicular torsion is difficult to make when it is complicated by vasculitis of the testis. Since both conditions can occur simultaneously, torsion of the testis must be considered and surgical exploration performed whenever acute testicular pain and swelling occur during the course of the Sch\u00f6nlein-Henoch syndrome. Two patients with this syndrome as well as scrotal and testicular involvement are described."} {"id": "PMID:1255895", "title": "Diagnostic features of tumors of the lower thoracic sympathetic chain.", "content": "Four cases of sympathetic neural tumors of the most inferior portion of the thoracic sympathetic chain are presented. The location of each tumor was such that a primary adrenal tumor might have been considered. However, each tumor was associated with erosion of the ipsilateral lower ribs or vertebral pedicles. Such radiologic findings indicate a primary posterior mediastinal tumor and primary exploration should be transthoracic.", "contents": "Diagnostic features of tumors of the lower thoracic sympathetic chain. Four cases of sympathetic neural tumors of the most inferior portion of the thoracic sympathetic chain are presented. The location of each tumor was such that a primary adrenal tumor might have been considered. However, each tumor was associated with erosion of the ipsilateral lower ribs or vertebral pedicles. Such radiologic findings indicate a primary posterior mediastinal tumor and primary exploration should be transthoracic."} {"id": "PMID:1255896", "title": "Combined adrenorenal fusion and adrenohepatic adhesion: a case report with review of the literature and discussion of pathogenesis.", "content": "The second case of combined adrenorenal fusion and adrenohepatic adhesion on the right side is reported. It is hypothesized that the basic lesion underlying this innocuous anomaly rests in the periadrenal mesenchyme. In the case of fusion of adrenal with kidney or liver the mesenchymal defect causes 1) retardation of capsule formation with parenchymal mixing and 2) failure of local differentiation into fetal and later adult fat cells. In the case of adhesion of adrenal to kidney or liver there is no retardation of capsule formation with parenchymal mixing but only failure to differentiate locally into fat cells. Consequently, there is no physical separation of these organs by interposition of fat cells and there is variable party-wall sharing of the capsule.", "contents": "Combined adrenorenal fusion and adrenohepatic adhesion: a case report with review of the literature and discussion of pathogenesis. The second case of combined adrenorenal fusion and adrenohepatic adhesion on the right side is reported. It is hypothesized that the basic lesion underlying this innocuous anomaly rests in the periadrenal mesenchyme. In the case of fusion of adrenal with kidney or liver the mesenchymal defect causes 1) retardation of capsule formation with parenchymal mixing and 2) failure of local differentiation into fetal and later adult fat cells. In the case of adhesion of adrenal to kidney or liver there is no retardation of capsule formation with parenchymal mixing but only failure to differentiate locally into fat cells. Consequently, there is no physical separation of these organs by interposition of fat cells and there is variable party-wall sharing of the capsule."} {"id": "PMID:1255897", "title": "Simple renal cyst and high renin hypertension cured by cyst decompression.", "content": "A case of renin elevated hypertension cured by cyst decompression is presented. The proposed mechanism is segmental renal ischemia produced by the cyst. Renal cyst evaluation should include renin studies if hypertension is present.", "contents": "Simple renal cyst and high renin hypertension cured by cyst decompression. A case of renin elevated hypertension cured by cyst decompression is presented. The proposed mechanism is segmental renal ischemia produced by the cyst. Renal cyst evaluation should include renin studies if hypertension is present."} {"id": "PMID:1255898", "title": "Transcatheter biopsy of renal carcinoma invading the inferior vena cava.", "content": "Transcatheter biopsy is presented as an alternate method of obtaining a histopathologic diagnosis in cases with evidence of direct neoplastic intravascular involvement and when conventional biopsy methods may be contraindicated.", "contents": "Transcatheter biopsy of renal carcinoma invading the inferior vena cava. Transcatheter biopsy is presented as an alternate method of obtaining a histopathologic diagnosis in cases with evidence of direct neoplastic intravascular involvement and when conventional biopsy methods may be contraindicated."} {"id": "PMID:1255899", "title": "Ureteral obstruction and pyelonephritis caused by an inguinal hernia: report of a case.", "content": "An elderly man had pyelonephritis and sepsis owing to ureteral obstruction. Retrograde pyelography showed entrapment of the right ureter in an inguinal hernia. This condition, which may be congenital or acquired, should be considered before herniorrhapy is performed and as a possible cause of ureteral obstruction.", "contents": "Ureteral obstruction and pyelonephritis caused by an inguinal hernia: report of a case. An elderly man had pyelonephritis and sepsis owing to ureteral obstruction. Retrograde pyelography showed entrapment of the right ureter in an inguinal hernia. This condition, which may be congenital or acquired, should be considered before herniorrhapy is performed and as a possible cause of ureteral obstruction."} {"id": "PMID:1255900", "title": "Pyeloureteral filling defects associated with systemic anticoagulation: a case report.", "content": "The etiology of pyeloureteritis cystica has long been attributed to chronic infection and inflammation. A case is presented that is unique in that the acute onset and the rapid resolution of pyeloureteral filling defects in this patient were documented by radiography. There is no evidence of antecedent or concurrent infection in this patient. The disease occurred subsequent to the initiation of heparin therapy for suspected pelvic thrombophlebitis and cleared rapidly subsequent to its discontinuation. The rate of resolution of the radiographic findings may be helpful in distinguishing between true pyeloureteritis cystica and submucosal hemorrhage.", "contents": "Pyeloureteral filling defects associated with systemic anticoagulation: a case report. The etiology of pyeloureteritis cystica has long been attributed to chronic infection and inflammation. A case is presented that is unique in that the acute onset and the rapid resolution of pyeloureteral filling defects in this patient were documented by radiography. There is no evidence of antecedent or concurrent infection in this patient. The disease occurred subsequent to the initiation of heparin therapy for suspected pelvic thrombophlebitis and cleared rapidly subsequent to its discontinuation. The rate of resolution of the radiographic findings may be helpful in distinguishing between true pyeloureteritis cystica and submucosal hemorrhage."} {"id": "PMID:1255901", "title": "Carcinoma of the urachus: its demonstration by pelvic pneumography.", "content": "Carcinoma of the urachus is an uncommon neoplasm that usually presents a diagnostic problem. A case of urachal carcinoma visualized by pelvic pneumography is reported. The clinical and radiological features of this lesion are briefly discussed.", "contents": "Carcinoma of the urachus: its demonstration by pelvic pneumography. Carcinoma of the urachus is an uncommon neoplasm that usually presents a diagnostic problem. A case of urachal carcinoma visualized by pelvic pneumography is reported. The clinical and radiological features of this lesion are briefly discussed."} {"id": "PMID:1255902", "title": "Genitourinary tract anomalies in lobster claw syndrome.", "content": "A child with ectrodactyly or lobster claw syndrome and bilateral ureterovesical junction obstruction is described. The embryogenesis of the kidney and the limb buds suggest that a close association exists between these 2 conditions. Therefore, it is important to investigate the urinary tract in all patients with limb deformities.", "contents": "Genitourinary tract anomalies in lobster claw syndrome. A child with ectrodactyly or lobster claw syndrome and bilateral ureterovesical junction obstruction is described. The embryogenesis of the kidney and the limb buds suggest that a close association exists between these 2 conditions. Therefore, it is important to investigate the urinary tract in all patients with limb deformities."} {"id": "PMID:1255906", "title": "Lymphocystis disease in the winter flounder, Pseudopleuronectes americanus.", "content": "Nodular lesions on the fins of winter flounder, Pseudopleuronemphocystis disease. Hypertrophied, encapsulated connective tissue cells contained cytoplasmic inclusions composed of icosahedral virus particles. The winter flounder is a new host for lymphocystis disease and is the second flatfish in the western North Atlantic to have the disease.", "contents": "Lymphocystis disease in the winter flounder, Pseudopleuronectes americanus. Nodular lesions on the fins of winter flounder, Pseudopleuronemphocystis disease. Hypertrophied, encapsulated connective tissue cells contained cytoplasmic inclusions composed of icosahedral virus particles. The winter flounder is a new host for lymphocystis disease and is the second flatfish in the western North Atlantic to have the disease."} {"id": "PMID:1255907", "title": "A relationship between avian carcasses and living invertebrates in the epizootiology of avian botulism.", "content": "A survey of the sources of Clostridium botulinum type C toxin possibly utilized as food by aquatic birds in an epizootic area of avian botulism in northern Utah showed that living aquatic and terrestrial invertebrates normally found in close association with dead, decomposing birds commonly carried the toxin. Of 461 samples associated with 21 species of avian carcasses, 198 were toxin-positive. Invertebrate species not normally scavengers of vertebrate tissues were less commonly and less highly toxic, particularly when captured 30 cm or more from a carcass; six of 237 samples of such aquatic invertebrates low-level toxin. Of the species tested, blow fly larvae (Calliphoridae) were the most consistently and highly toxic, although others, particularly adult and larval stages of several species of beetles (Coleoptera), contained toxin at levels probably significant in the epizootiology of the disease. An estimated 0.05 to 0.25 g of the most toxic fly larvae or 15 g of the most toxic beetles tested carried a mediam lethal dose for an adult mallard duck. Examination of stomach contents of aquatic birds dead of botulism showed that some had consumed invertebrates.", "contents": "A relationship between avian carcasses and living invertebrates in the epizootiology of avian botulism. A survey of the sources of Clostridium botulinum type C toxin possibly utilized as food by aquatic birds in an epizootic area of avian botulism in northern Utah showed that living aquatic and terrestrial invertebrates normally found in close association with dead, decomposing birds commonly carried the toxin. Of 461 samples associated with 21 species of avian carcasses, 198 were toxin-positive. Invertebrate species not normally scavengers of vertebrate tissues were less commonly and less highly toxic, particularly when captured 30 cm or more from a carcass; six of 237 samples of such aquatic invertebrates low-level toxin. Of the species tested, blow fly larvae (Calliphoridae) were the most consistently and highly toxic, although others, particularly adult and larval stages of several species of beetles (Coleoptera), contained toxin at levels probably significant in the epizootiology of the disease. An estimated 0.05 to 0.25 g of the most toxic fly larvae or 15 g of the most toxic beetles tested carried a mediam lethal dose for an adult mallard duck. Examination of stomach contents of aquatic birds dead of botulism showed that some had consumed invertebrates."} {"id": "PMID:1255908", "title": "The effects of lead poisoning on various plasma constituents in the Canada goose.", "content": "Plasma glucose, free fatty acid and uric acid levels were measured in lead-poisoned Canada geese (Branta canadensis). Although plasma glucose levels were only slightly elevated, uric acid was significantly higher and free fatty acids were significantly lower. Altered plasma levels were attributed to increased protein catabolism and perhaps renal disfunction. Plasma level of growth hormone and prolactin was assessed by radioimmunoassay. Growth hormone remained unchanged while prolactin was unusually high. The increased prolactin levels may reflect an effort to stabilize free fatty acids.", "contents": "The effects of lead poisoning on various plasma constituents in the Canada goose. Plasma glucose, free fatty acid and uric acid levels were measured in lead-poisoned Canada geese (Branta canadensis). Although plasma glucose levels were only slightly elevated, uric acid was significantly higher and free fatty acids were significantly lower. Altered plasma levels were attributed to increased protein catabolism and perhaps renal disfunction. Plasma level of growth hormone and prolactin was assessed by radioimmunoassay. Growth hormone remained unchanged while prolactin was unusually high. The increased prolactin levels may reflect an effort to stabilize free fatty acids."} {"id": "PMID:1255909", "title": "Infection and mortality in captive wild-trapped canvasback ducks.", "content": "Fungal, bacterial and malarial infections, as well as malnutrition caused heavy mortality in a group of wild-trapped canvasbacks (Aythya valisineria) held in 10 X 3 X 2 m open-water pens. Deaths occurred between 21 and 158 days after confinement and were associated with infections of Aspergillus fumigatus, Escherichia coli, Staphylococcus sp., Streptococcus sp., Klebsiella sp., Enterobacter sp., and Plasmodium sp. Infection and mortality was believed to result from reduced resistance associated with confinement. Fourteen canvasbacks released onto large ponds survived throughout the period during which the penned birds died.", "contents": "Infection and mortality in captive wild-trapped canvasback ducks. Fungal, bacterial and malarial infections, as well as malnutrition caused heavy mortality in a group of wild-trapped canvasbacks (Aythya valisineria) held in 10 X 3 X 2 m open-water pens. Deaths occurred between 21 and 158 days after confinement and were associated with infections of Aspergillus fumigatus, Escherichia coli, Staphylococcus sp., Streptococcus sp., Klebsiella sp., Enterobacter sp., and Plasmodium sp. Infection and mortality was believed to result from reduced resistance associated with confinement. Fourteen canvasbacks released onto large ponds survived throughout the period during which the penned birds died."} {"id": "PMID:1255910", "title": "Fluorosis in black-tailed deer.", "content": "Marked dental disfigurement and abnormal tooth wear patterns were observed in black-tailed deer (Odocoileus hemionus columbianus) taken from an area near an industrial fluoride source in northwestern Washington. Fluoride levels in the bones of these deer were from 10 to 35 times higher than levels in the bones of normal animals. These levels are similar to those associated with fluorosis of cattle.", "contents": "Fluorosis in black-tailed deer. Marked dental disfigurement and abnormal tooth wear patterns were observed in black-tailed deer (Odocoileus hemionus columbianus) taken from an area near an industrial fluoride source in northwestern Washington. Fluoride levels in the bones of these deer were from 10 to 35 times higher than levels in the bones of normal animals. These levels are similar to those associated with fluorosis of cattle."} {"id": "PMID:1255911", "title": "Lesions associated with Orthohalarachne attenuata (Halarachnidae) in the northern fur seal (Callorhinus ursinus).", "content": "In northern fur seals (Callorhinus ursinus) up to at least 4 years of age there is virtually 100% prevalence of infestation with the nasal mite Orthohalarachne attenuata. Although clinical observations and gross examination indicate that the condition is not serious, some erosion and inflammation of the nasal turbinates and nasopharynx were seen associated with mites in histological sections.", "contents": "Lesions associated with Orthohalarachne attenuata (Halarachnidae) in the northern fur seal (Callorhinus ursinus). In northern fur seals (Callorhinus ursinus) up to at least 4 years of age there is virtually 100% prevalence of infestation with the nasal mite Orthohalarachne attenuata. Although clinical observations and gross examination indicate that the condition is not serious, some erosion and inflammation of the nasal turbinates and nasopharynx were seen associated with mites in histological sections."} {"id": "PMID:1255912", "title": "A trematode from the round window of an Atlantic Bottlenosed dolphin's ear.", "content": "A trematode from the family Nasitrematidae Yamaguti 1951 was found adhered to the round window in the inner ear of a Bottlenosed Dolphin (Tursiops truncatus). The possibility that parasites could be responsible for changes in acoustic behavior and hearing loss is discussed.", "contents": "A trematode from the round window of an Atlantic Bottlenosed dolphin's ear. A trematode from the family Nasitrematidae Yamaguti 1951 was found adhered to the round window in the inner ear of a Bottlenosed Dolphin (Tursiops truncatus). The possibility that parasites could be responsible for changes in acoustic behavior and hearing loss is discussed."} {"id": "PMID:1255913", "title": "Influence of rainfall on lungworm infections in bighorn sheep.", "content": "From 1959 through 1968, lungs from 124 Rocky Mountain bighorn sheep (Ovis c. canadensis) from the Sun River herd in western Montana were examined for lungworm infections. All lungs were infected with Protostrongylus stilesi and 104 (84%) contained concurrent infections of P. stilesi and P. rushi. Significant correlations were observed between levels of lungworm infection and total rainfall during April, May, and June of each year. An explanation of this in terms of terrestrial snail (intermediate host) populations and a suggestion for the possible use of these data in developing a predictive model for forecasting lungworm levels for use in in bighorn sheep management are given.", "contents": "Influence of rainfall on lungworm infections in bighorn sheep. From 1959 through 1968, lungs from 124 Rocky Mountain bighorn sheep (Ovis c. canadensis) from the Sun River herd in western Montana were examined for lungworm infections. All lungs were infected with Protostrongylus stilesi and 104 (84%) contained concurrent infections of P. stilesi and P. rushi. Significant correlations were observed between levels of lungworm infection and total rainfall during April, May, and June of each year. An explanation of this in terms of terrestrial snail (intermediate host) populations and a suggestion for the possible use of these data in developing a predictive model for forecasting lungworm levels for use in in bighorn sheep management are given."} {"id": "PMID:1255914", "title": "Some observations on chronic leptospiral carrier state in gerbils experimentally infected with Leptospira grippotyphosa.", "content": "Leptospiruria with persistent microscopic agglutinating antibody titers were maintained in gerbils that became carriers following experimental infection with Leptospira grippotyphosa, strain F 4397. Leptospires were isolated from kidneys of a gerbil which died 28 months after experimental inoculation.", "contents": "Some observations on chronic leptospiral carrier state in gerbils experimentally infected with Leptospira grippotyphosa. Leptospiruria with persistent microscopic agglutinating antibody titers were maintained in gerbils that became carriers following experimental infection with Leptospira grippotyphosa, strain F 4397. Leptospires were isolated from kidneys of a gerbil which died 28 months after experimental inoculation."} {"id": "PMID:1255915", "title": "Ixodes scapularis Say on white-tailed deer (Odocoileus virginianus) from Long Point, Ontario.", "content": "Ixodes scapularis Say was the only species of tick found on white-tailed deer, Odocoileus virginianus, collected at Long Point, Ontario from October 1972 to August 1973. Adults were most abundant from September 1972 to April 1973. Larvae were found throughout the study period except during February. Nymphs were scarce during winter months but fairly common during spring and summer. Most adults were found on the neck and shoulders. Larvae occurred mainly on lower regions of the body and nymphs mainly on the head, shoulders, forelegs and brisket.", "contents": "Ixodes scapularis Say on white-tailed deer (Odocoileus virginianus) from Long Point, Ontario. Ixodes scapularis Say was the only species of tick found on white-tailed deer, Odocoileus virginianus, collected at Long Point, Ontario from October 1972 to August 1973. Adults were most abundant from September 1972 to April 1973. Larvae were found throughout the study period except during February. Nymphs were scarce during winter months but fairly common during spring and summer. Most adults were found on the neck and shoulders. Larvae occurred mainly on lower regions of the body and nymphs mainly on the head, shoulders, forelegs and brisket."} {"id": "PMID:1255916", "title": "Some hematologic values of bison from five areas of the United States.", "content": "Seventeen hematologic values of the American Bison (Bison bison) from five areas of the United States were determined using standard techniques. The means of the principal blood measurements for all bison were 10.08 +/- 1.43 million erythrocytes/mm3, 8.03 +/- 1.41 thousand leukocytes/mm3, 16.92 +/- 1.43 gm % hemoglobin and 47.11 +/- 4.06% hematocrit. There was a significant variation (P less than 0.05) among age groups of males for erythrocytes, neutrophils, lymphocytes and monocytes. However, no significant variation between female age groups or sexes was found for any of the blood cell values determined.", "contents": "Some hematologic values of bison from five areas of the United States. Seventeen hematologic values of the American Bison (Bison bison) from five areas of the United States were determined using standard techniques. The means of the principal blood measurements for all bison were 10.08 +/- 1.43 million erythrocytes/mm3, 8.03 +/- 1.41 thousand leukocytes/mm3, 16.92 +/- 1.43 gm % hemoglobin and 47.11 +/- 4.06% hematocrit. There was a significant variation (P less than 0.05) among age groups of males for erythrocytes, neutrophils, lymphocytes and monocytes. However, no significant variation between female age groups or sexes was found for any of the blood cell values determined."} {"id": "PMID:1255917", "title": "Blood changes in brook trout induced by infection with Aeromonas salmonicida.", "content": "Furunculosis was induced in brook trout, Salvelinus fontinalis, by experimental inoculation with Aeromonas salmonicida. Total protein, hemoglobin, sialic acid, fatty acids, triglycerides, cholesterol, inorganic-phosphorus, acid-soluble phosphorus, and lipid-phosphorus decreased in the blood of the infected fish while amino acids, urea, total creatinine, ammonia, and glucose increased. Pyruvic acid, lactic acid, and ascorbic acid values showed no significant change.", "contents": "Blood changes in brook trout induced by infection with Aeromonas salmonicida. Furunculosis was induced in brook trout, Salvelinus fontinalis, by experimental inoculation with Aeromonas salmonicida. Total protein, hemoglobin, sialic acid, fatty acids, triglycerides, cholesterol, inorganic-phosphorus, acid-soluble phosphorus, and lipid-phosphorus decreased in the blood of the infected fish while amino acids, urea, total creatinine, ammonia, and glucose increased. Pyruvic acid, lactic acid, and ascorbic acid values showed no significant change."} {"id": "PMID:1255918", "title": "Mycotic flora in the lower digestive tract of feral pigeons (Columba livia) in the El Paso, Texas area.", "content": "Fourteen species of fungus were isolated from the lower digestive tract of 39 of 80 pigeons. Sixteen pigeons had concurrent isolations while two harbored three species. Fungi isolated were Allescheria boydii, Aspergillus spp., Candida krusei, Chrysosporium spp., Geotrichum candidum, Mucor spp., Paeciliomyces spp., Penicillium spp., Rhizopus spp., Rhodotorula spp., Scopulariopsis spp., Streptomyces spp., and Trichosporon cutaneum. There was no apparent evidence that these fungi were associated with clinical disease in any of the pigeons.", "contents": "Mycotic flora in the lower digestive tract of feral pigeons (Columba livia) in the El Paso, Texas area. Fourteen species of fungus were isolated from the lower digestive tract of 39 of 80 pigeons. Sixteen pigeons had concurrent isolations while two harbored three species. Fungi isolated were Allescheria boydii, Aspergillus spp., Candida krusei, Chrysosporium spp., Geotrichum candidum, Mucor spp., Paeciliomyces spp., Penicillium spp., Rhizopus spp., Rhodotorula spp., Scopulariopsis spp., Streptomyces spp., and Trichosporon cutaneum. There was no apparent evidence that these fungi were associated with clinical disease in any of the pigeons."} {"id": "PMID:1255919", "title": "Renal capillariasis in the small Indian mongoose, Herpestes auropunctatus.", "content": "A Capillaria sp. was recovered from the kidneys of 28 (93.3%) of 30 small Indian mongooses (Herpestes auropunctus) collected in St. Lucia, West Indies. The nematodes were embedded within distended pelvic fornices of the kidney and surrounded by accumulations of eggs. A chronic, low-level inflammation of the transitional epithelium was characterized by hyperplasia, giant cells surrounding embedded eggs and a plasmacytic infiltration. This is the first record of a capillarid nematode from the kidney of the mongoose.", "contents": "Renal capillariasis in the small Indian mongoose, Herpestes auropunctatus. A Capillaria sp. was recovered from the kidneys of 28 (93.3%) of 30 small Indian mongooses (Herpestes auropunctus) collected in St. Lucia, West Indies. The nematodes were embedded within distended pelvic fornices of the kidney and surrounded by accumulations of eggs. A chronic, low-level inflammation of the transitional epithelium was characterized by hyperplasia, giant cells surrounding embedded eggs and a plasmacytic infiltration. This is the first record of a capillarid nematode from the kidney of the mongoose."} {"id": "PMID:1255920", "title": "Quantitative determination of serum immunoglobulins in chronic obstructive pulmonary diseases with special reference to cor pulmonale.", "content": "In patients with chronic obstructive pulmonary disease, quantitative analysis of serum IgG, IgA and IgM were carried out by use of the radial immunodiffusion method. The concentration of IgE in sera was also determined by the radioactive radial immunodiffusion method. The mean value of serum IgG level in the group of cor pulmonale was higher than that in groups of emphysema, asthma and normal subjects. The mean value of serum IgA level was higher in two groups of cor pulmonale and emphysema than in the group of asthma and of normal subjects. There was no difference of serum IgM levels between these four groups. The mean value of serum IgE in the group of allergic asthma was higher than that in the group of non-allergic asthma or normal subjects and an elevated serum IgE level was also found in patients with cor pulmonale. Findings of this study suggested that the raised level of serum IgG in patients with chronic cor pulmonale might reflect production of antiheart antibodies against cardiac tissue.", "contents": "Quantitative determination of serum immunoglobulins in chronic obstructive pulmonary diseases with special reference to cor pulmonale. In patients with chronic obstructive pulmonary disease, quantitative analysis of serum IgG, IgA and IgM were carried out by use of the radial immunodiffusion method. The concentration of IgE in sera was also determined by the radioactive radial immunodiffusion method. The mean value of serum IgG level in the group of cor pulmonale was higher than that in groups of emphysema, asthma and normal subjects. The mean value of serum IgA level was higher in two groups of cor pulmonale and emphysema than in the group of asthma and of normal subjects. There was no difference of serum IgM levels between these four groups. The mean value of serum IgE in the group of allergic asthma was higher than that in the group of non-allergic asthma or normal subjects and an elevated serum IgE level was also found in patients with cor pulmonale. Findings of this study suggested that the raised level of serum IgG in patients with chronic cor pulmonale might reflect production of antiheart antibodies against cardiac tissue."} {"id": "PMID:1255921", "title": "Renin release and the juxtaglomerular apparatus in chronic renal failure due to glomerulonephritis.", "content": "Changes in renin release with decreasing renal function and juxtaglomerular apparatus in chronic renal failure due to glomerulonephritis were studied. Renin production was still remaining in the contracted kidneys and its release could be stimulated by various stimulations, although the macula densa didn't seem to play an important role in renin release in the contracted kidneys.", "contents": "Renin release and the juxtaglomerular apparatus in chronic renal failure due to glomerulonephritis. Changes in renin release with decreasing renal function and juxtaglomerular apparatus in chronic renal failure due to glomerulonephritis were studied. Renin production was still remaining in the contracted kidneys and its release could be stimulated by various stimulations, although the macula densa didn't seem to play an important role in renin release in the contracted kidneys."} {"id": "PMID:1255922", "title": "Possible existence of prorenin in rabbit renal cortex.", "content": "The possible existence of prorenin (inactive form of renin) in rabbit renal cortex was studied. Renal cortex was homogenized with 0.25 M sucrose. Following centrifugation at 800 g for 10 min, the supernatant (Fraction H) was centrifuged at 20,000 g for 20 min. The pellet (Fraction G) was separated from soluble fraction (Fraction S). Intravenous injection of non-treated Fraction G caused a little blood pressure elevation in rats. However, the pressor activity of the same amount of Fraction G which was frozen and thawed 5 times previously was more than 10 times as that of non-treated one. The renin activity in preincubated fraction G with Fraction S was 2-fold the summation of the activity of renin in each fraction, when measured using indirect method. Fraction S lost not only the renin activity but also the renin activating activity when heated for 5 min at 100 degrees C. Exposure to pH 3.5 made no influence on renin activity in either Fraction G and S.", "contents": "Possible existence of prorenin in rabbit renal cortex. The possible existence of prorenin (inactive form of renin) in rabbit renal cortex was studied. Renal cortex was homogenized with 0.25 M sucrose. Following centrifugation at 800 g for 10 min, the supernatant (Fraction H) was centrifuged at 20,000 g for 20 min. The pellet (Fraction G) was separated from soluble fraction (Fraction S). Intravenous injection of non-treated Fraction G caused a little blood pressure elevation in rats. However, the pressor activity of the same amount of Fraction G which was frozen and thawed 5 times previously was more than 10 times as that of non-treated one. The renin activity in preincubated fraction G with Fraction S was 2-fold the summation of the activity of renin in each fraction, when measured using indirect method. Fraction S lost not only the renin activity but also the renin activating activity when heated for 5 min at 100 degrees C. Exposure to pH 3.5 made no influence on renin activity in either Fraction G and S."} {"id": "PMID:1255923", "title": "Plasma renin activity in acute respiratory acidosis.", "content": "Plasma renin activity in acute respiratory acidosis and the effect of hexamethonium bromide was studied. Fourteen mongrel dogs were anesthetized with sodium pentobarbiturate and given 5% and 15% carbon dioxide in room air, successively. Hexamethonium bromide was given to 8 dogs prior to carbon dioxide inhalation. Arterial carbon dioxide partial pressure, oxygen partial pressure and pH were measured in addition to the determination of plasma renin activity. Plasma renin activity was elevated in moderate respiratory acidosis induced by 5% carbon dioxide inhalation from 37.5 +/- 8.8 ng/ml to 52.8 +/- 7.0 ng/ml. In severe respiratory acidosis produced by 15% carbon dioxide inhalation, plasma renin activity elevated further to 85.8 +/- 8.6 ng/ml. Plasma renin activity of the hexamethonium bromide treated dogs was 19.0 +/- 3.5 ng/ml during room air breathing. The activity was elevated to 26.0 +/- 6.4 ng/ml by 5% carbon dioxide inhalation and further to 57.3 +/- 5.9 ng/ml by 15% carbon dioxide inhalation. These findings may suggest that the elevation of plasma renin activity in acute respiratory acidosis induced by carbon dioxide inhalation is independent from sympathetic stimulation.", "contents": "Plasma renin activity in acute respiratory acidosis. Plasma renin activity in acute respiratory acidosis and the effect of hexamethonium bromide was studied. Fourteen mongrel dogs were anesthetized with sodium pentobarbiturate and given 5% and 15% carbon dioxide in room air, successively. Hexamethonium bromide was given to 8 dogs prior to carbon dioxide inhalation. Arterial carbon dioxide partial pressure, oxygen partial pressure and pH were measured in addition to the determination of plasma renin activity. Plasma renin activity was elevated in moderate respiratory acidosis induced by 5% carbon dioxide inhalation from 37.5 +/- 8.8 ng/ml to 52.8 +/- 7.0 ng/ml. In severe respiratory acidosis produced by 15% carbon dioxide inhalation, plasma renin activity elevated further to 85.8 +/- 8.6 ng/ml. Plasma renin activity of the hexamethonium bromide treated dogs was 19.0 +/- 3.5 ng/ml during room air breathing. The activity was elevated to 26.0 +/- 6.4 ng/ml by 5% carbon dioxide inhalation and further to 57.3 +/- 5.9 ng/ml by 15% carbon dioxide inhalation. These findings may suggest that the elevation of plasma renin activity in acute respiratory acidosis induced by carbon dioxide inhalation is independent from sympathetic stimulation."} {"id": "PMID:1255924", "title": "Newly constructed spatial circumference electrocardiograph.", "content": "Spatial circumference electrocardiograph which could compute the length of the spatial circumference of each vectorcardiographic loop and record the pattern of the increment of the vectorcardiographic are very easily and accurately on the bed side was constructed. CR differentiating circuits with three sets of the different time constant were used for the differentiations. Vector sum circuits applying absolute value operations reported by Imai and Nguyen Phuoc (1972) were used in this apparatus and the simplification of the consitution of the circuits and the excellent results were obtained. Examples of the spatial circumference ECG recorded in a normal subject and some pathologic conditions were demonstrated.", "contents": "Newly constructed spatial circumference electrocardiograph. Spatial circumference electrocardiograph which could compute the length of the spatial circumference of each vectorcardiographic loop and record the pattern of the increment of the vectorcardiographic are very easily and accurately on the bed side was constructed. CR differentiating circuits with three sets of the different time constant were used for the differentiations. Vector sum circuits applying absolute value operations reported by Imai and Nguyen Phuoc (1972) were used in this apparatus and the simplification of the consitution of the circuits and the excellent results were obtained. Examples of the spatial circumference ECG recorded in a normal subject and some pathologic conditions were demonstrated."} {"id": "PMID:1255926", "title": "Immunological reactions involving leukocytes: II. Studies of a patient with multiple transfusion-induced allogeneic antibodies to leukocytes.", "content": "A patient who had received multiple transfusions for the treatment of aplastic anemia was studied. There were antibodies against allogeneic granulocytes and lymphocytes in her serum. Granulocyte antibodies were detected by their effect on phagocytosis-associated hexose monophosphate shunt (HMS) activity, while lymphocyte antibodies were detected by their cytotoxicity. Granulocyte antibodies were in the IgG and IgM fractions. Prior absorption of this patient's serum with granulocytes or lymphocytes from a single donor eliminated its inhibitory effect on phagocytosis-associated HMS activity of that donor's granulocytes. Studies of many unrelated donors and the patient's seven siblings revealed that her serum inhibited the granulocytes from all of these individuals with the sole exception of the granulocytes harvested from her one HL-A identical sister. The evidence suggests that this patient's antibodies are directed against HL-A antigens or some cell surface antigens coded for by loci closely linked to the HL-A genes.", "contents": "Immunological reactions involving leukocytes: II. Studies of a patient with multiple transfusion-induced allogeneic antibodies to leukocytes. A patient who had received multiple transfusions for the treatment of aplastic anemia was studied. There were antibodies against allogeneic granulocytes and lymphocytes in her serum. Granulocyte antibodies were detected by their effect on phagocytosis-associated hexose monophosphate shunt (HMS) activity, while lymphocyte antibodies were detected by their cytotoxicity. Granulocyte antibodies were in the IgG and IgM fractions. Prior absorption of this patient's serum with granulocytes or lymphocytes from a single donor eliminated its inhibitory effect on phagocytosis-associated HMS activity of that donor's granulocytes. Studies of many unrelated donors and the patient's seven siblings revealed that her serum inhibited the granulocytes from all of these individuals with the sole exception of the granulocytes harvested from her one HL-A identical sister. The evidence suggests that this patient's antibodies are directed against HL-A antigens or some cell surface antigens coded for by loci closely linked to the HL-A genes."} {"id": "PMID:1255927", "title": "Continuous trans-physeal traction: a simple method of bone lengthening.", "content": "Leg length increments utilizing continuous traction across the epiphyseal plate of growing puppies produces a cleavage fracture at the level of the primary metaphyseal trabeculae which neither anatomically nor physiologically alters the growth plate. These fractures heal readily and growth resumes following removal of the traction device. This method is relatively atraumatic to the extremity. It does not require an open operation and the controlled distraction rate has not caused neurological or vascular complications. The study was designed to determine the anatomic site of fracture; no attempt was made to achieve maximal leg length increments.", "contents": "Continuous trans-physeal traction: a simple method of bone lengthening. Leg length increments utilizing continuous traction across the epiphyseal plate of growing puppies produces a cleavage fracture at the level of the primary metaphyseal trabeculae which neither anatomically nor physiologically alters the growth plate. These fractures heal readily and growth resumes following removal of the traction device. This method is relatively atraumatic to the extremity. It does not require an open operation and the controlled distraction rate has not caused neurological or vascular complications. The study was designed to determine the anatomic site of fracture; no attempt was made to achieve maximal leg length increments."} {"id": "PMID:1255928", "title": "The use of intramuscular propantheline in the short bowel syndrome.", "content": "A patient is presented with the short bowel syndrome who because of massive diarrhea was unable to maintain fluid and electrolyte balance with the aid of the usual antidiarrhea drugs. Her bowel remnant consisted of approximately 155 cm of proximal jejunum. Intramuscular propantheline has allowed this patient to function normally for the past 36 months. Balance studies are presented to document the benefit of this drug. Propantheline's effectiveness is probably secondary to its marked slowing of intestinal motility.", "contents": "The use of intramuscular propantheline in the short bowel syndrome. A patient is presented with the short bowel syndrome who because of massive diarrhea was unable to maintain fluid and electrolyte balance with the aid of the usual antidiarrhea drugs. Her bowel remnant consisted of approximately 155 cm of proximal jejunum. Intramuscular propantheline has allowed this patient to function normally for the past 36 months. Balance studies are presented to document the benefit of this drug. Propantheline's effectiveness is probably secondary to its marked slowing of intestinal motility."} {"id": "PMID:1255999", "title": "[Central core disease with \"structured cores\" in type II-fibers (author's transl)].", "content": "Report on a sporadic case with congenital slowly progressive neuromuscular disease. Light microscopic, ultrastructural and histochemical changes of muscle biopsy reveal the characteristics of central core disease with \"structured cores\" in type II-fibers.", "contents": "[Central core disease with \"structured cores\" in type II-fibers (author's transl)]. Report on a sporadic case with congenital slowly progressive neuromuscular disease. Light microscopic, ultrastructural and histochemical changes of muscle biopsy reveal the characteristics of central core disease with \"structured cores\" in type II-fibers."} {"id": "PMID:1255998", "title": "The morphological and clinical course of the different forms of glomerulonephritis.", "content": "From repeat biopsies of 291 patients with glomerulonephritis, the clinical and morphological course of the individual forms of glomerulonephritis were compared with one another. From these results we concluded that: 1. Every form of glomerulonephritis has in all probability its individual course and prognosis, which can only be very slightly influenced by therapy. 2. The prognosis is considerably worsened, when either hypertension develops or tubular lesions in the morphological sense of an acute renal failure.", "contents": "The morphological and clinical course of the different forms of glomerulonephritis. From repeat biopsies of 291 patients with glomerulonephritis, the clinical and morphological course of the individual forms of glomerulonephritis were compared with one another. From these results we concluded that: 1. Every form of glomerulonephritis has in all probability its individual course and prognosis, which can only be very slightly influenced by therapy. 2. The prognosis is considerably worsened, when either hypertension develops or tubular lesions in the morphological sense of an acute renal failure."} {"id": "PMID:1256000", "title": "[Diurnal variation in the urinary excretion of vanilmandelic acid and aldosterone in normal and hypertensive persons (author's transl)].", "content": "The excretion of creatinine, VMA, and aldosterone was measured in the urine of 14 normal and 25 persons with stable essential hypertension during a day time (7.00-23.00 hrs) and a night time (23.00-7.00 hrs) period. Excretion of VMA and aldosterone per hour in the two groups was lower during the night period than during the day. No significant difference existed between the excretion values of both groups. Night/day rations for the excretion of VMA and of aldosterone respectively, per mg of creatinine excreted were calculated for each subject. In the normal group the night/day ratios of aldosterone excretion showed a significant correlation to the corresponding ratios of VMA excretion; such correlation was not found in the hypertensive group. The fact that a correlation was observed in the normal group is compatible with the hypothesis that catecholamines are involved in the regulation of the renin-angiotensin-aldosterone system. Lack of correlation in the group of hypertensive does not as yet allow any conclusions. In two patients with primary hyperaldosteronism, the aldosterone excretion during the night was relatively more elevated than in the day.", "contents": "[Diurnal variation in the urinary excretion of vanilmandelic acid and aldosterone in normal and hypertensive persons (author's transl)]. The excretion of creatinine, VMA, and aldosterone was measured in the urine of 14 normal and 25 persons with stable essential hypertension during a day time (7.00-23.00 hrs) and a night time (23.00-7.00 hrs) period. Excretion of VMA and aldosterone per hour in the two groups was lower during the night period than during the day. No significant difference existed between the excretion values of both groups. Night/day rations for the excretion of VMA and of aldosterone respectively, per mg of creatinine excreted were calculated for each subject. In the normal group the night/day ratios of aldosterone excretion showed a significant correlation to the corresponding ratios of VMA excretion; such correlation was not found in the hypertensive group. The fact that a correlation was observed in the normal group is compatible with the hypothesis that catecholamines are involved in the regulation of the renin-angiotensin-aldosterone system. Lack of correlation in the group of hypertensive does not as yet allow any conclusions. In two patients with primary hyperaldosteronism, the aldosterone excretion during the night was relatively more elevated than in the day."} {"id": "PMID:1256001", "title": "[Aggressive emperipolesis in chronic hepatitis (author's transl)].", "content": "The penetration and destruction of hepatocytes by lymphocytes (aggressive emperipolesis) has been described and examined quantitatively in biopsy specimens of chronic hepatitis. In 48 cases of chronic persistent hepatitis, the aggressive emperipolesis was rare and, obviously, not of great importance: sometimes there was no emperipolesis at all. In 36 cases of chronic aggressive hepatitis, however, emperioplesis was always evident, usually even to a very high extent.", "contents": "[Aggressive emperipolesis in chronic hepatitis (author's transl)]. The penetration and destruction of hepatocytes by lymphocytes (aggressive emperipolesis) has been described and examined quantitatively in biopsy specimens of chronic hepatitis. In 48 cases of chronic persistent hepatitis, the aggressive emperipolesis was rare and, obviously, not of great importance: sometimes there was no emperipolesis at all. In 36 cases of chronic aggressive hepatitis, however, emperioplesis was always evident, usually even to a very high extent."} {"id": "PMID:1256002", "title": "Red cell aggregation in blood flow. I. New methods of quantification.", "content": "The rheological behavior of normal and pathological red cell aggregates in viscometric flow (artificial flow in cone plate chamber) is studied by direct microscopy, (rheoscopy) viscometry and photometry. Marked differences between normal and pathological blood are measured in the microrheological properties of red cell aggregates; only discreet differences are measured by blood viscometry (macrorheology). Both in normal and abnormal blood, red cell aggregation is a reversible process in the presence of adequate shear forces; their respective influences on apparent blood viscosity at low rates of shear are complex functions of shear rate, shear time, hematocrit and plasma viscosities. Pathological red cell aggregation (RCA) forms more rapidly and extensively than normal RCA. The pathological aggregates frequently have a tendency to grow at low rates of shear and they are highly shear resistant.", "contents": "Red cell aggregation in blood flow. I. New methods of quantification. The rheological behavior of normal and pathological red cell aggregates in viscometric flow (artificial flow in cone plate chamber) is studied by direct microscopy, (rheoscopy) viscometry and photometry. Marked differences between normal and pathological blood are measured in the microrheological properties of red cell aggregates; only discreet differences are measured by blood viscometry (macrorheology). Both in normal and abnormal blood, red cell aggregation is a reversible process in the presence of adequate shear forces; their respective influences on apparent blood viscosity at low rates of shear are complex functions of shear rate, shear time, hematocrit and plasma viscosities. Pathological red cell aggregation (RCA) forms more rapidly and extensively than normal RCA. The pathological aggregates frequently have a tendency to grow at low rates of shear and they are highly shear resistant."} {"id": "PMID:1256003", "title": "Red cell aggregation in blood flow. II. Effect on apparent viscosity of blood.", "content": "The apparent viscosity of blood strongly increases at low shear in rotational viscometers, this phenomenon is based on the reversible formation of red cell aggregates. The magnitude of this increase strongly depends on the hematocrit value, on plasma viscosity and lastly on the microrheological properties of the aggregates. The independent measurement of the microrheological behavior and the effects on viscosity allows a detailed analysis of the hemodynamic effects of red cell aggregates under defined flow conditions in vivo. The comparative analysis shows that the conventional viscometry strongly underestimates the rheological differences between normal and pathologically intensified aggregation. Based on detailed analysis under defined flow conditions in vitro, the biological significance of viscometric results and the hemodynamic relevance of red cell aggregates are discussed.", "contents": "Red cell aggregation in blood flow. II. Effect on apparent viscosity of blood. The apparent viscosity of blood strongly increases at low shear in rotational viscometers, this phenomenon is based on the reversible formation of red cell aggregates. The magnitude of this increase strongly depends on the hematocrit value, on plasma viscosity and lastly on the microrheological properties of the aggregates. The independent measurement of the microrheological behavior and the effects on viscosity allows a detailed analysis of the hemodynamic effects of red cell aggregates under defined flow conditions in vivo. The comparative analysis shows that the conventional viscometry strongly underestimates the rheological differences between normal and pathologically intensified aggregation. Based on detailed analysis under defined flow conditions in vitro, the biological significance of viscometric results and the hemodynamic relevance of red cell aggregates are discussed."} {"id": "PMID:1256004", "title": "Erythrocyte sedimentation rate and C-reactive protein.", "content": "C-reactive protein (CRP) was isolated from pleura exudate of patients with metastasing cancer and added to plasma of healthy blood donors. Only the addition of excessive amounts of CRP (220 mg/ml) caused a notable increase in erythrocyte sedimentation rate. An immunoelectrophoretic method for the simultaneous quantitative determination of CRP together with C 3 or other acute phase reactants is described.", "contents": "Erythrocyte sedimentation rate and C-reactive protein. C-reactive protein (CRP) was isolated from pleura exudate of patients with metastasing cancer and added to plasma of healthy blood donors. Only the addition of excessive amounts of CRP (220 mg/ml) caused a notable increase in erythrocyte sedimentation rate. An immunoelectrophoretic method for the simultaneous quantitative determination of CRP together with C 3 or other acute phase reactants is described."} {"id": "PMID:1256005", "title": "Somatostatin: a potent inhibitor of ACTH-hypersecretion in adrenal insufficiency.", "content": "Somatostatin (250 mug as a bolus i.v. and 250 mug as a 1-hr infusion) was administered to 5 patients with adrenal insufficiency of different origin. In each patient a sustained, progressive fall in plasma ACTH was observed during the infusion period. The mean maximal reduction in plasma ACTH was 43.8 +/- 5.9%. After cessation of the somatostatin infusion there was a rise of plasma ACTH to starting levels within 1/2 hour. These findings suggest that somatostatin is a potent inhibitor of ACTH secretion, however, only in a condition in which glucocorticoids are lacking.", "contents": "Somatostatin: a potent inhibitor of ACTH-hypersecretion in adrenal insufficiency. Somatostatin (250 mug as a bolus i.v. and 250 mug as a 1-hr infusion) was administered to 5 patients with adrenal insufficiency of different origin. In each patient a sustained, progressive fall in plasma ACTH was observed during the infusion period. The mean maximal reduction in plasma ACTH was 43.8 +/- 5.9%. After cessation of the somatostatin infusion there was a rise of plasma ACTH to starting levels within 1/2 hour. These findings suggest that somatostatin is a potent inhibitor of ACTH secretion, however, only in a condition in which glucocorticoids are lacking."} {"id": "PMID:1256006", "title": "[Renal function during passive orthostasis (author's transl)].", "content": "Glomerular filtration rate (GRF) as measured by inulin clearance and renal plasma flow (RPF) as measured by PAH clearance were determined in 9 mountaineers before and during suspension. The two step permanent infusion technique was employed for 3 periods of 8 min. GRF decreased from 123.0 +/- 14.9 ml/min to 25.3 +/- 3.9 ml/min and RPF from 791.0 +/- 101.0 ml/min to 129.0 +/- 20.4 ml/min within 24 min. These results are consistent with the occurrence of acute renal failure in mountain climbers after free suspension on the rope even after long periods.", "contents": "[Renal function during passive orthostasis (author's transl)]. Glomerular filtration rate (GRF) as measured by inulin clearance and renal plasma flow (RPF) as measured by PAH clearance were determined in 9 mountaineers before and during suspension. The two step permanent infusion technique was employed for 3 periods of 8 min. GRF decreased from 123.0 +/- 14.9 ml/min to 25.3 +/- 3.9 ml/min and RPF from 791.0 +/- 101.0 ml/min to 129.0 +/- 20.4 ml/min within 24 min. These results are consistent with the occurrence of acute renal failure in mountain climbers after free suspension on the rope even after long periods."} {"id": "PMID:1256007", "title": "Myelopoietic cell proliferation in granulocytopenia of refractory anaemia and preleukemia states with hyper-plastic bone marrow.", "content": "Myelopoiesis in healthy subjects and in 8 cases of refractory anaemia or preleukemia states was studied by the combined cytophotometric-autoradirgraphic method. Granulocytopenia was present in 7 of 8 cases. The results can be summarized as follows: 1. Mature myelocytes of healthy persons are a mainly differentiating cell population with a low labelling index (3-10%) and a high incidence in G1-Phase. 2. The proliferating immature granulopoietic cells of the patients with neutropenia showed a reduced labelling index with 3H-thymidine as a result of an arrest of these cells in G1 (6 of 8 cases). 3. A similar result was obtained in the study of the hyperplastic myelopoiesis of an other patient with preleukemia and normal granulocyte count in peripheral blood, with the disturbance of cell proliferation preceding the symptom neutropenia. 4. Finally in only one case an increased frequency of myelopoietic cells in G2-phase was found suggesting an arrest of cell proliferation in the premitotic phase.", "contents": "Myelopoietic cell proliferation in granulocytopenia of refractory anaemia and preleukemia states with hyper-plastic bone marrow. Myelopoiesis in healthy subjects and in 8 cases of refractory anaemia or preleukemia states was studied by the combined cytophotometric-autoradirgraphic method. Granulocytopenia was present in 7 of 8 cases. The results can be summarized as follows: 1. Mature myelocytes of healthy persons are a mainly differentiating cell population with a low labelling index (3-10%) and a high incidence in G1-Phase. 2. The proliferating immature granulopoietic cells of the patients with neutropenia showed a reduced labelling index with 3H-thymidine as a result of an arrest of these cells in G1 (6 of 8 cases). 3. A similar result was obtained in the study of the hyperplastic myelopoiesis of an other patient with preleukemia and normal granulocyte count in peripheral blood, with the disturbance of cell proliferation preceding the symptom neutropenia. 4. Finally in only one case an increased frequency of myelopoietic cells in G2-phase was found suggesting an arrest of cell proliferation in the premitotic phase."} {"id": "PMID:1256008", "title": "[Free and template-bound RNA polymerase in normal and leukaemic human lymphocytes (author's transl)].", "content": "Specific activities are determined of two functional fractions of alpha-amanitin sensitive DNA-dependent RNA polymerases in nucleic from human normal and chronic lymphocytic leukemia lymphocytes. Specific activity of \"free\" RNA polymerase in CLL corresponds ot 0.133 pmoles (3H)-UMP/10(6) cells as compared to 0.209 in normals. Activities of the \"engaged\" enzymes are 0.139 in CLL and 0.132 in normals. \"Free\" enzymes in NL and CLL are completely inhibited by 400 ng/ml Rifamycin AF/013, while the \"engaged\" enzymes exhibit 70% of their original activity. 1.0 ng/ml alpha-amanitin suppress 50% of the activity of the \"free\" enzyme in CLL. The \"free\" enzyme in NL and the \"engaged\" enzymes in NL and CLL do not show any residual activity in the presence of 1.0 ng/ml alpha-amanitin.", "contents": "[Free and template-bound RNA polymerase in normal and leukaemic human lymphocytes (author's transl)]. Specific activities are determined of two functional fractions of alpha-amanitin sensitive DNA-dependent RNA polymerases in nucleic from human normal and chronic lymphocytic leukemia lymphocytes. Specific activity of \"free\" RNA polymerase in CLL corresponds ot 0.133 pmoles (3H)-UMP/10(6) cells as compared to 0.209 in normals. Activities of the \"engaged\" enzymes are 0.139 in CLL and 0.132 in normals. \"Free\" enzymes in NL and CLL are completely inhibited by 400 ng/ml Rifamycin AF/013, while the \"engaged\" enzymes exhibit 70% of their original activity. 1.0 ng/ml alpha-amanitin suppress 50% of the activity of the \"free\" enzyme in CLL. The \"free\" enzyme in NL and the \"engaged\" enzymes in NL and CLL do not show any residual activity in the presence of 1.0 ng/ml alpha-amanitin."} {"id": "PMID:1256009", "title": "[Laxative abuse, plasma potassium levels and chronic interstitial nephritis due to phenacetin abuse (author's transl)].", "content": "In 154 patients with phenacetin nephropathy and in 26 patients with phenacetin abuse but without nephropathy a laxative abuse was observed in 3.2% and 15.4%, hypokalemia (3.5 maequ/l or less) in 9.1% and 3.9, respectively. The mean plasma potassium concentration was normal in both groups (4.45 and 4.22 maequ/l, respectively). These data do not support the recently proposed hypothesis that the simultaneous abuse of laxatives contributes to the development of analgesic nephropathy, and that the absence of laxative intake might explain the lack of renal damage in some phenacetin abusers. Although it cannot be excluded that long-standing potassium deficiency in consequence of an abuse of laxatives or diuretics exerts an additional nephrotoxic effect in some cases, this mechanism seems not to be involved in the majority of patients with phenacetin nephropathy.", "contents": "[Laxative abuse, plasma potassium levels and chronic interstitial nephritis due to phenacetin abuse (author's transl)]. In 154 patients with phenacetin nephropathy and in 26 patients with phenacetin abuse but without nephropathy a laxative abuse was observed in 3.2% and 15.4%, hypokalemia (3.5 maequ/l or less) in 9.1% and 3.9, respectively. The mean plasma potassium concentration was normal in both groups (4.45 and 4.22 maequ/l, respectively). These data do not support the recently proposed hypothesis that the simultaneous abuse of laxatives contributes to the development of analgesic nephropathy, and that the absence of laxative intake might explain the lack of renal damage in some phenacetin abusers. Although it cannot be excluded that long-standing potassium deficiency in consequence of an abuse of laxatives or diuretics exerts an additional nephrotoxic effect in some cases, this mechanism seems not to be involved in the majority of patients with phenacetin nephropathy."} {"id": "PMID:1256010", "title": "Breeding and fertility of the Egyptian spiny mouse, Acomys cahirinus: effect of different environments.", "content": "2 years experience with Acomys in one laboratory confirmed the slow breeding rate found by other workers. On moving the animals to another laboratory there was a 2-5 fold increase in breeding rate. The most likely explanation of this change was the presence of copper in the drinking water at the 1st laboratory, due to the use of copper water pipes. The data relating to maintenance and breeding of acomys for 2 years at the 2nd laboratory were analyzed to provide a more representative picture of the species.", "contents": "Breeding and fertility of the Egyptian spiny mouse, Acomys cahirinus: effect of different environments. 2 years experience with Acomys in one laboratory confirmed the slow breeding rate found by other workers. On moving the animals to another laboratory there was a 2-5 fold increase in breeding rate. The most likely explanation of this change was the presence of copper in the drinking water at the 1st laboratory, due to the use of copper water pipes. The data relating to maintenance and breeding of acomys for 2 years at the 2nd laboratory were analyzed to provide a more representative picture of the species."} {"id": "PMID:1256011", "title": "A survey of laboratory animal disease in Kenya.", "content": "Diseases and infections diagnosed in laboratory mice, rats, guinea-pigs, golden hamsters and rabbits at the Veterinary Research Laboratory, Kabete, Kenya, are listed and discussed. Zoonoses encountered included salmonellosis and lymphocytic choriomeningitis. A number of traditionally recognised conditions were recorded but there were some notable omissions. The changing picture in laboratory animal science in East Africa is outlined and attention is drawn to the need for work on related diseases and infections.", "contents": "A survey of laboratory animal disease in Kenya. Diseases and infections diagnosed in laboratory mice, rats, guinea-pigs, golden hamsters and rabbits at the Veterinary Research Laboratory, Kabete, Kenya, are listed and discussed. Zoonoses encountered included salmonellosis and lymphocytic choriomeningitis. A number of traditionally recognised conditions were recorded but there were some notable omissions. The changing picture in laboratory animal science in East Africa is outlined and attention is drawn to the need for work on related diseases and infections."} {"id": "PMID:1256013", "title": "Value of combining the erythrocyte sedimentation rate test with tuberculin testing in the control of tuberculosis in baboons.", "content": "2 batches of baboon infected with tuberculosis were subjected to serial tests with human and bovine tuberculin, while erythrocyte sedimentation rates were estimated concurrently. In the very early stages most but not all reacted to human tuberculin while fewer responded to bovine material. After further development of the disease, tuberculin tests remained positive while sedimentation rates were raised by 10-30 mm per hour. By the time early spread had occurred response to tuberculin was absent but sedimentation rates tended to increase. Advanced cases always tuberculin negative but sedimentation rates were in excess of 50 mm per hour. Such animals were always in good physical condition and represented an insidious danger to other animals and staff in contact with them. Clinical examination failed to reveal cases of tuberculosis except in the terminal stages and no cases were diagnosed by radiography. 2 animals died from apparent anaphylaxis following inoculation of both types of tuberculin. Results showed that use of one or other of these tests alone would not have made possible the elimination of infection.", "contents": "Value of combining the erythrocyte sedimentation rate test with tuberculin testing in the control of tuberculosis in baboons. 2 batches of baboon infected with tuberculosis were subjected to serial tests with human and bovine tuberculin, while erythrocyte sedimentation rates were estimated concurrently. In the very early stages most but not all reacted to human tuberculin while fewer responded to bovine material. After further development of the disease, tuberculin tests remained positive while sedimentation rates were raised by 10-30 mm per hour. By the time early spread had occurred response to tuberculin was absent but sedimentation rates tended to increase. Advanced cases always tuberculin negative but sedimentation rates were in excess of 50 mm per hour. Such animals were always in good physical condition and represented an insidious danger to other animals and staff in contact with them. Clinical examination failed to reveal cases of tuberculosis except in the terminal stages and no cases were diagnosed by radiography. 2 animals died from apparent anaphylaxis following inoculation of both types of tuberculin. Results showed that use of one or other of these tests alone would not have made possible the elimination of infection."} {"id": "PMID:1256014", "title": "Problems associated with the identification of bordetella bronchiseptica.", "content": "Bordetella bronchiseptica, isolated from rodent nasopharygeal swabs, failed to produce characteristic colonies after 24 hours incubation at 37 degrees C. 4-7 days incubation at 37 degrees C was required to achieve positive motility test results, when isolates later identified as B. bronchiseptica were tested by Craigie tube and soft agar stab methods. The biochemical tests used to identify suspected B. bronchiseptica are specified.", "contents": "Problems associated with the identification of bordetella bronchiseptica. Bordetella bronchiseptica, isolated from rodent nasopharygeal swabs, failed to produce characteristic colonies after 24 hours incubation at 37 degrees C. 4-7 days incubation at 37 degrees C was required to achieve positive motility test results, when isolates later identified as B. bronchiseptica were tested by Craigie tube and soft agar stab methods. The biochemical tests used to identify suspected B. bronchiseptica are specified."} {"id": "PMID:1256032", "title": "Kibbutz and city children: a comparative study of syntactic and articulatory abilities.", "content": "This study investigated whether there were any significant differences between the syntactic and articulatory development of kibbutz and city children in Israel. Ninety children between the ages of three and four and a half years were administered a Hebrew adaptation of the Northwestern Syntax Screening Test and a Hebrew articulation test. Receptive and expressive language ability at this age were found to be superior among kibbutz children. There was no significant difference in the overall number of articulation errors made: however, there was a significantly higher rate of sibilant disorders among the kibbutz children.", "contents": "Kibbutz and city children: a comparative study of syntactic and articulatory abilities. This study investigated whether there were any significant differences between the syntactic and articulatory development of kibbutz and city children in Israel. Ninety children between the ages of three and four and a half years were administered a Hebrew adaptation of the Northwestern Syntax Screening Test and a Hebrew articulation test. Receptive and expressive language ability at this age were found to be superior among kibbutz children. There was no significant difference in the overall number of articulation errors made: however, there was a significantly higher rate of sibilant disorders among the kibbutz children."} {"id": "PMID:1256033", "title": "A comparison of impairments in verbal comprehension, speech, reading, and writing in adult aphasics.", "content": "A clinical population of 44 aphasics was rated on the severity of impairment of functional communication in each of four language modalities: verbal comprehension, speech, reading, and writing. Comparisons are made of the severity of impairment in each pair of language modalities for the subjects as a group and for individual subjects. Correlations between severity ratings in each pair of language modalities are also presented. The results indicate that all modalities are impaired to approximately the same degree and that differences between severity ratings across all modalities are small for the large majority of aphasic subjects. Writing is usually the most severely impaired modality. A discussion is presented reviewing the important influences that methodology has on the data obtained and on the inferences which may be drawn about the nature of aphasia as a uni- or multimodality impairment.", "contents": "A comparison of impairments in verbal comprehension, speech, reading, and writing in adult aphasics. A clinical population of 44 aphasics was rated on the severity of impairment of functional communication in each of four language modalities: verbal comprehension, speech, reading, and writing. Comparisons are made of the severity of impairment in each pair of language modalities for the subjects as a group and for individual subjects. Correlations between severity ratings in each pair of language modalities are also presented. The results indicate that all modalities are impaired to approximately the same degree and that differences between severity ratings across all modalities are small for the large majority of aphasic subjects. Writing is usually the most severely impaired modality. A discussion is presented reviewing the important influences that methodology has on the data obtained and on the inferences which may be drawn about the nature of aphasia as a uni- or multimodality impairment."} {"id": "PMID:1256038", "title": "Pure tone-spondee threshold relationships in functional hearing loss: a hypothesis.", "content": "A hypothesis is offered to account for the fact that in functional hearing loss, spondee threshold is frequently significantly lower than the pure-tone average. The hypothesis has three basic components: (1) that patients with functional hearing loss use a loudness criterion in making response decisions to suprathreshold stimuli; (2) that, at suprathreshold levels, pure tones and spondee words appear equally loud at equal sound pressure levels, and (3) that calibration values employed in pure-tone and speech audiometry contribute to the aberrant speech-pure tone relationship. Factors that may confound the speech-pure tone relationship are discussed as are the clinical and research implication of the hypothesis.", "contents": "Pure tone-spondee threshold relationships in functional hearing loss: a hypothesis. A hypothesis is offered to account for the fact that in functional hearing loss, spondee threshold is frequently significantly lower than the pure-tone average. The hypothesis has three basic components: (1) that patients with functional hearing loss use a loudness criterion in making response decisions to suprathreshold stimuli; (2) that, at suprathreshold levels, pure tones and spondee words appear equally loud at equal sound pressure levels, and (3) that calibration values employed in pure-tone and speech audiometry contribute to the aberrant speech-pure tone relationship. Factors that may confound the speech-pure tone relationship are discussed as are the clinical and research implication of the hypothesis."} {"id": "PMID:1256039", "title": "Distinctive features in speech pathology: phonology or phonemics?", "content": "Distinctive feature is not a unique concept within linguistic theory. It has two distinct bases: phonemic theory and generative theory. Phonemic theory assumes a direct correspondence between distinctive features (the elements of phonemes) and the speech signal. Although this assumption can be shown to be incorrect, it seems to be the one most widely held in speech science. Generative theory, on the other hand, assumes no such direct relation and consequently can account for certain linguistic phenomena that phonemic theory cannot. This theory then seems to be preferable to phonemic theory for a featural analysis of misarticulation. However, there is a problem. Chomsky and Halle's system (generative theory) as it stands does not deal with the link between what it conceives to be the lowest level of linguistic structure (the phonetic matrix) and speech production. Therefore, Chomsky and Halle's distinctive features cannot be applied fruitfully to all instances of misarticulation. The discrepancy that exists between phonological structure and the speech signal must be accounted for in a theory of speech production. This can be accomplished by recognizing a production matrix below the phonetic matrix, where segments are described in terms of production features. The crucial point is that no one-to-one relationship necessarily exists between distinctive features and production features.", "contents": "Distinctive features in speech pathology: phonology or phonemics? Distinctive feature is not a unique concept within linguistic theory. It has two distinct bases: phonemic theory and generative theory. Phonemic theory assumes a direct correspondence between distinctive features (the elements of phonemes) and the speech signal. Although this assumption can be shown to be incorrect, it seems to be the one most widely held in speech science. Generative theory, on the other hand, assumes no such direct relation and consequently can account for certain linguistic phenomena that phonemic theory cannot. This theory then seems to be preferable to phonemic theory for a featural analysis of misarticulation. However, there is a problem. Chomsky and Halle's system (generative theory) as it stands does not deal with the link between what it conceives to be the lowest level of linguistic structure (the phonetic matrix) and speech production. Therefore, Chomsky and Halle's distinctive features cannot be applied fruitfully to all instances of misarticulation. The discrepancy that exists between phonological structure and the speech signal must be accounted for in a theory of speech production. This can be accomplished by recognizing a production matrix below the phonetic matrix, where segments are described in terms of production features. The crucial point is that no one-to-one relationship necessarily exists between distinctive features and production features."} {"id": "PMID:1256040", "title": "Some common problems in the design and conduct of experiments in stuttering.", "content": "This paper focuses upon and discusses some common problems in the design and conduct of various types of stuttering research. Apparent problems are dealt with under the following headings: (1) circular definitions of hypothetical constructs, (2) operational definitions of stuttering that lack denotative specificity, (3) research designs based on invalid assumptions about stuttering, and (4) omitted or inadequate measurement of speech rate in operant studies of stuttering. In each of these sections, a problem is identified and then some suggestions are offered for resolving it. This article pertains to research that underlies clinical management, and some implications for clinicians are drawn.", "contents": "Some common problems in the design and conduct of experiments in stuttering. This paper focuses upon and discusses some common problems in the design and conduct of various types of stuttering research. Apparent problems are dealt with under the following headings: (1) circular definitions of hypothetical constructs, (2) operational definitions of stuttering that lack denotative specificity, (3) research designs based on invalid assumptions about stuttering, and (4) omitted or inadequate measurement of speech rate in operant studies of stuttering. In each of these sections, a problem is identified and then some suggestions are offered for resolving it. This article pertains to research that underlies clinical management, and some implications for clinicians are drawn."} {"id": "PMID:1256041", "title": "Response-contingent small-step treatment: performance-based communication intervention.", "content": "Response-contingent small-step treatment is a structured clinical methodology developed for use in the management of brain-injured communication-disturbed adults. Treatment planning includes the determination of target behavior hierarchies, criterion levels of patient performance, and planned response contingencies. Treatment forms are employed to enable ease in scoring patient response, systematic treatment planning, and objective data retrieval for charting.", "contents": "Response-contingent small-step treatment: performance-based communication intervention. Response-contingent small-step treatment is a structured clinical methodology developed for use in the management of brain-injured communication-disturbed adults. Treatment planning includes the determination of target behavior hierarchies, criterion levels of patient performance, and planned response contingencies. Treatment forms are employed to enable ease in scoring patient response, systematic treatment planning, and objective data retrieval for charting."} {"id": "PMID:1256042", "title": "Verbal versus tangible reward for children who stutter.", "content": "The results of several previous attempts to modify the speech of stuttering children suggest that tangible (as opposed to verbal) rewards are efficient forms of positive reinforcement. The purpose of this study was to investigate the relative effectiveness of these two forms of positive reinforcement with young stuttering subjects. Each of three stuttering children was seen for a base rate session, three experimental sessions, and a carry-over session. Experimental sessions were preceded by verbal instructions explaining the response contingency, and subjects selected their own verbal and tangible reinforcers. Results revealed that both verbal and tangible reinforcements were equally effective in modifying the speech of the three subjects. The possibility is discussed that the effectiveness of verbal and tangible rewards with young stuttering subjects can be explained by (1) selection of the rewards by the subjects; (2) reinforcement of easily identifiable behavior; and (3) subject awareness of the response contingency.", "contents": "Verbal versus tangible reward for children who stutter. The results of several previous attempts to modify the speech of stuttering children suggest that tangible (as opposed to verbal) rewards are efficient forms of positive reinforcement. The purpose of this study was to investigate the relative effectiveness of these two forms of positive reinforcement with young stuttering subjects. Each of three stuttering children was seen for a base rate session, three experimental sessions, and a carry-over session. Experimental sessions were preceded by verbal instructions explaining the response contingency, and subjects selected their own verbal and tangible reinforcers. Results revealed that both verbal and tangible reinforcements were equally effective in modifying the speech of the three subjects. The possibility is discussed that the effectiveness of verbal and tangible rewards with young stuttering subjects can be explained by (1) selection of the rewards by the subjects; (2) reinforcement of easily identifiable behavior; and (3) subject awareness of the response contingency."} {"id": "PMID:1256043", "title": "The effects of age on the diagnostic utility of the rollover phenomenon.", "content": "Articulation curves were constructed for 32 elderly listeners with hearing according to previously established decadal age norms. Each function was specifically examined for the presence of rollover, a previously determined indicator of retrocochlear pathology. Rollover exhibited by six subjects was an age-related phenomenon. It is suggested that normal neural degeneration concomitant with the aging process is responsible for this auditory behavior and that clinical significance of the rollover phenomenon is greatly reduced when dealing with the aged population. Implications for the use of the rollover index are also discussed.", "contents": "The effects of age on the diagnostic utility of the rollover phenomenon. Articulation curves were constructed for 32 elderly listeners with hearing according to previously established decadal age norms. Each function was specifically examined for the presence of rollover, a previously determined indicator of retrocochlear pathology. Rollover exhibited by six subjects was an age-related phenomenon. It is suggested that normal neural degeneration concomitant with the aging process is responsible for this auditory behavior and that clinical significance of the rollover phenomenon is greatly reduced when dealing with the aged population. Implications for the use of the rollover index are also discussed."} {"id": "PMID:1256044", "title": "Paroxysmal ataxic dysarthria.", "content": "This report reviews 13 cases in which a dysarthria appeared, remitted, and reappeared within seconds. The speech pattern of each case was characteristic of ataxic dysarthria. A cinefluorographic film for one of the subjects provided a rare opportunity to study the articulatory dynamics of this disorder. Multiple sclerosis either was given as a diagnosis or was strongly suspected in each case, and carbamazepine has been an effective treatment. Speculations concerning the origin of the paroxysmal and ataxic character of the dysarthria are presented along with a preliminary checklist for identifying the disorder.", "contents": "Paroxysmal ataxic dysarthria. This report reviews 13 cases in which a dysarthria appeared, remitted, and reappeared within seconds. The speech pattern of each case was characteristic of ataxic dysarthria. A cinefluorographic film for one of the subjects provided a rare opportunity to study the articulatory dynamics of this disorder. Multiple sclerosis either was given as a diagnosis or was strongly suspected in each case, and carbamazepine has been an effective treatment. Speculations concerning the origin of the paroxysmal and ataxic character of the dysarthria are presented along with a preliminary checklist for identifying the disorder."} {"id": "PMID:1256058", "title": "Investigations of the possible role of proteases in altering surface proteins of virally transformed hamster fibroblasts.", "content": "Virally transformed fibroblasts have on their surfaces zero or reduced amounts of a large external transformation-sensitive (LETS) glycoprotein. This protein is extremely sensitive to proteolysis. When prelabeled normal fibroblasts are cocultivated with transformed cells, the LETS glycoprotein of the normal cells shows an increased rate of turnover. Experiments are described which investigate the possibility that this phenomenon and the absence of LETS glycoprotein are due to proteolysis by the transformed cells. In particular, the role of plasminogen activation is examined by the use of protease inhibitors and plasminogen-depleted serum. It is concluded that activation of plasminogen is not required for the disappearance of the LETS glycoprotein although the involvement of other proteases cannot be ruled out. The role of proteases in affecting cell growth and behavior is discussed.", "contents": "Investigations of the possible role of proteases in altering surface proteins of virally transformed hamster fibroblasts. Virally transformed fibroblasts have on their surfaces zero or reduced amounts of a large external transformation-sensitive (LETS) glycoprotein. This protein is extremely sensitive to proteolysis. When prelabeled normal fibroblasts are cocultivated with transformed cells, the LETS glycoprotein of the normal cells shows an increased rate of turnover. Experiments are described which investigate the possibility that this phenomenon and the absence of LETS glycoprotein are due to proteolysis by the transformed cells. In particular, the role of plasminogen activation is examined by the use of protease inhibitors and plasminogen-depleted serum. It is concluded that activation of plasminogen is not required for the disappearance of the LETS glycoprotein although the involvement of other proteases cannot be ruled out. The role of proteases in affecting cell growth and behavior is discussed."} {"id": "PMID:1256059", "title": "Selective modification of cell surface proteins and thymidine transport in hamster cells exposed to cholera toxin.", "content": "The increased adherence and morphological response which occurs in Chinese hamster ovary cells as a result of exposure to cholera toxin is paralleled by modification in the relative exposure of outer proteins. Mild proteolysis treatment of the cells prelabeled with [3H] glucosamine reveals a markedly different kinetics of release of external glycopeptides as a result of exposure to cholera toxin. Selective alterations in external tyrosyl-rich proteins can also be detected by lactoperoxidase-catalyzed radioiodination. The above modifications are accompanied by a decrease in the rate of thymidine uptake by toxin-treated cells.", "contents": "Selective modification of cell surface proteins and thymidine transport in hamster cells exposed to cholera toxin. The increased adherence and morphological response which occurs in Chinese hamster ovary cells as a result of exposure to cholera toxin is paralleled by modification in the relative exposure of outer proteins. Mild proteolysis treatment of the cells prelabeled with [3H] glucosamine reveals a markedly different kinetics of release of external glycopeptides as a result of exposure to cholera toxin. Selective alterations in external tyrosyl-rich proteins can also be detected by lactoperoxidase-catalyzed radioiodination. The above modifications are accompanied by a decrease in the rate of thymidine uptake by toxin-treated cells."} {"id": "PMID:1256060", "title": "Cell surface receptors and their dynamics on toxin-treated malignant cells.", "content": "The binding, mobility, and mode of cell entry of the plant toxin ricin (or RCAII) were investigated on susceptible and partially resistant murine cell lines. When susceptible cells (SV40-transformed 3T3 fibroblast cells and BW5147 lymphoma cells) were examined, ricin bound rapidly, induced endocytosis, and entered the cell cytoplasm via broken endocytotic vesicles to inhibit cell protein synthesis, as found previously (1). Addition of lactose within 15 min after initial ricin binding prevented toxicity. After this time lactose addition no longer blocked the inhibition of protein synthesis. In a partially resistant lymphoma (BW5147/RCA3) that shows only a slight reduction in the total number of ricin-binding sites, ricin bound rapidly to the cell surface, but was endocytosed significantly less at low ricin doses compared to its parental line, indicating a possible difference in cell surface behavior. The exposed surface proteins on the BW5147 parental and BW5147/RCA3 resistnat lines were examined by 125I-labeling utilizing lactoperoxidase-catalyzed iodination. The radiolabeled components were solubilized and separated by slab electrophoresis in sodium dodecyl sulfate. Autoradiograms of the slab gels indicated that two surface components of approximately 80,000 and 35,000 mol wt were much less exposed or were missing on the resistant line.", "contents": "Cell surface receptors and their dynamics on toxin-treated malignant cells. The binding, mobility, and mode of cell entry of the plant toxin ricin (or RCAII) were investigated on susceptible and partially resistant murine cell lines. When susceptible cells (SV40-transformed 3T3 fibroblast cells and BW5147 lymphoma cells) were examined, ricin bound rapidly, induced endocytosis, and entered the cell cytoplasm via broken endocytotic vesicles to inhibit cell protein synthesis, as found previously (1). Addition of lactose within 15 min after initial ricin binding prevented toxicity. After this time lactose addition no longer blocked the inhibition of protein synthesis. In a partially resistant lymphoma (BW5147/RCA3) that shows only a slight reduction in the total number of ricin-binding sites, ricin bound rapidly to the cell surface, but was endocytosed significantly less at low ricin doses compared to its parental line, indicating a possible difference in cell surface behavior. The exposed surface proteins on the BW5147 parental and BW5147/RCA3 resistnat lines were examined by 125I-labeling utilizing lactoperoxidase-catalyzed iodination. The radiolabeled components were solubilized and separated by slab electrophoresis in sodium dodecyl sulfate. Autoradiograms of the slab gels indicated that two surface components of approximately 80,000 and 35,000 mol wt were much less exposed or were missing on the resistant line."} {"id": "PMID:1256061", "title": "The expression and localization of surface neoantigens in transformed and untransformed cultured cells infected with avian tumor viruses.", "content": "The presence and localization of neoantigens induced in cultured cells, infected or transformed with avian tumor viruses (ATV), were studied ultrastructurally on carbon platinum replicas of cell surfaces. The use of antibody, labeled with hemocyanin molecules, provided sensitive detection and analysis of cell surface antigen distribution. The subgroup-specific antigens of the viral envelope were found in considerable amount in the plasma membranes of ATV-infected chick embryo fibroblasts. The distribution of these antigens over the cell surface, evaluated on cells which were prefixed with glutaraldehyde, was found to be diffuse with a greater density on the cell processes in some cells. Reaction of antibody to viral envelope antigens with living ATV-infected cells resulted in a number of patterns of redistribution of membrane antigen-antibody complexes (AAC). Redistribution occurred in symmetrical or asymmetrical modes. The former consisted of randomly oriented aggregates (patches) of AAC over the cell surface. The latter included: (a) linear accumulation of AAC at cell margins; and (b) condensation of compexes into one or more centers of coalescence. These observations could be made on chick embryo cells infected (but not transformed) by avian leukosis virus, or on cells oncogenically transformed by avian sarcoma virus. The regions of coalescence were suggestive of the \"capping\" phenomenon seen in other systems, and their formation was temporally correlated with endocytosis of labeled AAC and the gradual loss of AAC from the surface. The effects of several biologically perturbing substances on the processes of redistribution were investigated in ALV-infected fibroblasts. Sodium azide, puromycin, actinomycin D, and colchicine had no effect on either form of asymmetrical redistribution. Cytochalasin B (CB) and iodoacetic acid (IAA) appeared to have some effect on the marginal redistribution, and to completely prevent the condensation into foci of coalescence (FC). When treated with these compounds, reacted with antibody at low temperature, washed free of unbound antibody, and warmed at 37 degrees C, cells rapidly cleared their surfaces of AAC. This was not accompanied by formation of FC or endocytosis. In some of these cells, a distribution was observed which suggested a possible centrifugal flow of antigenic sites-perhaps an alternate route for disposal of AAC. None of the drugs tested affected symmetrical redistribution. Repeated attempts at detection and topographical analysis of a tumor-specific antigen on the surface of Rous sarcoma virus-transformed chicken and rat cells have provided no evidence for antibody to such an antigen in the serum of immunized animals. Autochthonous, homologous, and heterologous immunizations of chickens and rats did not produce a detectable antibody response to a virus-specific tumor surface antigen. Preliminary results, however, suggest the expression of an individual-specific (unique) tumor antigen on the surface of Rous sarcoma cells.", "contents": "The expression and localization of surface neoantigens in transformed and untransformed cultured cells infected with avian tumor viruses. The presence and localization of neoantigens induced in cultured cells, infected or transformed with avian tumor viruses (ATV), were studied ultrastructurally on carbon platinum replicas of cell surfaces. The use of antibody, labeled with hemocyanin molecules, provided sensitive detection and analysis of cell surface antigen distribution. The subgroup-specific antigens of the viral envelope were found in considerable amount in the plasma membranes of ATV-infected chick embryo fibroblasts. The distribution of these antigens over the cell surface, evaluated on cells which were prefixed with glutaraldehyde, was found to be diffuse with a greater density on the cell processes in some cells. Reaction of antibody to viral envelope antigens with living ATV-infected cells resulted in a number of patterns of redistribution of membrane antigen-antibody complexes (AAC). Redistribution occurred in symmetrical or asymmetrical modes. The former consisted of randomly oriented aggregates (patches) of AAC over the cell surface. The latter included: (a) linear accumulation of AAC at cell margins; and (b) condensation of compexes into one or more centers of coalescence. These observations could be made on chick embryo cells infected (but not transformed) by avian leukosis virus, or on cells oncogenically transformed by avian sarcoma virus. The regions of coalescence were suggestive of the \"capping\" phenomenon seen in other systems, and their formation was temporally correlated with endocytosis of labeled AAC and the gradual loss of AAC from the surface. The effects of several biologically perturbing substances on the processes of redistribution were investigated in ALV-infected fibroblasts. Sodium azide, puromycin, actinomycin D, and colchicine had no effect on either form of asymmetrical redistribution. Cytochalasin B (CB) and iodoacetic acid (IAA) appeared to have some effect on the marginal redistribution, and to completely prevent the condensation into foci of coalescence (FC). When treated with these compounds, reacted with antibody at low temperature, washed free of unbound antibody, and warmed at 37 degrees C, cells rapidly cleared their surfaces of AAC. This was not accompanied by formation of FC or endocytosis. In some of these cells, a distribution was observed which suggested a possible centrifugal flow of antigenic sites-perhaps an alternate route for disposal of AAC. None of the drugs tested affected symmetrical redistribution. Repeated attempts at detection and topographical analysis of a tumor-specific antigen on the surface of Rous sarcoma virus-transformed chicken and rat cells have provided no evidence for antibody to such an antigen in the serum of immunized animals. Autochthonous, homologous, and heterologous immunizations of chickens and rats did not produce a detectable antibody response to a virus-specific tumor surface antigen. Preliminary results, however, suggest the expression of an individual-specific (unique) tumor antigen on the surface of Rous sarcoma cells."} {"id": "PMID:1256062", "title": "The size of adenylate cyclase and guanylate cyclase from the rat renal medulla.", "content": "The size distribution of adenylate cyclase from the rat renal medulla solubilized with the nonionic detergents Triton X-100 and Lubrol PX was determined by gel filtration and by centrifugation in sucrose density gradients made up in H2O or D2O. The physical parameters of the predominant form in Triton X-100 are s20,w, 5.9S; Strokes radius, 62 A; partial specific volume (v), 0.74 ml/g; mass, 159,000 daltons; f/f0, 1.6; axial ratio (prolate ellipsoid), 11. For the minor form the values are: s20w, 3.0; Stokes radius, 28 A; mass, 38,000 daltons; f/f0, 1.2. The corresponding values determined in Lubrol PX are similar. The value for V for the enzyme indicates that it binds less than 0.2 mg detergent/mg protein. Since interactions with detergents probably substitute for interactions with lipids and hydrophobic amino acid side chains, these findings suggest that no more than 5% of the surface of adenylate cyclase is involved in hydrophobic interactions with other membrane components. Thus, most of the mass of the enzyme is not deeply embedded in the lipid bilayer of the plasma membrane. Similar studies have been performed on the soluble guanylate cyclase of the rat renal medulla. In the absence of detergent, the molecular properties of this enzyme are: s20w, 6.3S; Stokes radius, 54 A, V, 0.75 ml/g; mass, 154,000 daltons f/f0, 1.4; Axial ratio, 7. The addition of 0.1% Lubrol PX to this soluble enzyme increases it activity two- to fourfold and changes the physical properties to: s20,w, 5.5S; Stokes radius, 62 A; V, 0.74 ml/g; mass, 148,000 daltons, f/f0, 1.6; axial ratio, 11. These results show that Lubrol PX activates the enzyme by causing a conformational change with unfolding on the polypeptide chain. Guanylate cyclase from the particulate cell fraction can be solubilized with Lubrol PX but has properties quite different from those of the enzyme in the soluble cell fraction. It is a heterogeneous aggregate with s20,w, 10S; Stokes radius, 65 A; mass about 300,000 daltons. The conditions which solubilize guanylate cyclase also solubilize adenylate cyclase and the two activities can be separated on the same sucrose gradient.", "contents": "The size of adenylate cyclase and guanylate cyclase from the rat renal medulla. The size distribution of adenylate cyclase from the rat renal medulla solubilized with the nonionic detergents Triton X-100 and Lubrol PX was determined by gel filtration and by centrifugation in sucrose density gradients made up in H2O or D2O. The physical parameters of the predominant form in Triton X-100 are s20,w, 5.9S; Strokes radius, 62 A; partial specific volume (v), 0.74 ml/g; mass, 159,000 daltons; f/f0, 1.6; axial ratio (prolate ellipsoid), 11. For the minor form the values are: s20w, 3.0; Stokes radius, 28 A; mass, 38,000 daltons; f/f0, 1.2. The corresponding values determined in Lubrol PX are similar. The value for V for the enzyme indicates that it binds less than 0.2 mg detergent/mg protein. Since interactions with detergents probably substitute for interactions with lipids and hydrophobic amino acid side chains, these findings suggest that no more than 5% of the surface of adenylate cyclase is involved in hydrophobic interactions with other membrane components. Thus, most of the mass of the enzyme is not deeply embedded in the lipid bilayer of the plasma membrane. Similar studies have been performed on the soluble guanylate cyclase of the rat renal medulla. In the absence of detergent, the molecular properties of this enzyme are: s20w, 6.3S; Stokes radius, 54 A, V, 0.75 ml/g; mass, 154,000 daltons f/f0, 1.4; Axial ratio, 7. The addition of 0.1% Lubrol PX to this soluble enzyme increases it activity two- to fourfold and changes the physical properties to: s20,w, 5.5S; Stokes radius, 62 A; V, 0.74 ml/g; mass, 148,000 daltons, f/f0, 1.6; axial ratio, 11. These results show that Lubrol PX activates the enzyme by causing a conformational change with unfolding on the polypeptide chain. Guanylate cyclase from the particulate cell fraction can be solubilized with Lubrol PX but has properties quite different from those of the enzyme in the soluble cell fraction. It is a heterogeneous aggregate with s20,w, 10S; Stokes radius, 65 A; mass about 300,000 daltons. The conditions which solubilize guanylate cyclase also solubilize adenylate cyclase and the two activities can be separated on the same sucrose gradient."} {"id": "PMID:1256064", "title": "Occupational therapy treatment of the patient with thermally injured upper extremity.", "content": "Severe upper extremity burns may mean an indefinite interruption in the style of life to which an individual is accustomed, and the occupational therapist can help the thermally injured patient to regain purposeful activity. Even a simple temporary prosthesis for the amputee, enabling him to write (Fig. 12-17), permits meaningful activity that can reduce boredom, dependence, preoccupation with death, and depression. A vigorous progressive physical and occupational therapy program producing tangible results does more for the patient's morale than any verbal encouragement could possibly do. Finally, the therapist can be more than the \"mechanic\" of the burn team. In his daily contact with the patient, he can be a \"good listener\" to whom the patient can verbalize his hostility, anger, resentment, and fear. When appropriate, he may convey this information to the physician, who can help the patient gain insight into some of the problems manifested by his behavior.", "contents": "Occupational therapy treatment of the patient with thermally injured upper extremity. Severe upper extremity burns may mean an indefinite interruption in the style of life to which an individual is accustomed, and the occupational therapist can help the thermally injured patient to regain purposeful activity. Even a simple temporary prosthesis for the amputee, enabling him to write (Fig. 12-17), permits meaningful activity that can reduce boredom, dependence, preoccupation with death, and depression. A vigorous progressive physical and occupational therapy program producing tangible results does more for the patient's morale than any verbal encouragement could possibly do. Finally, the therapist can be more than the \"mechanic\" of the burn team. In his daily contact with the patient, he can be a \"good listener\" to whom the patient can verbalize his hostility, anger, resentment, and fear. When appropriate, he may convey this information to the physician, who can help the patient gain insight into some of the problems manifested by his behavior."} {"id": "PMID:1256066", "title": "Electrical injuries of the upper extremity.", "content": "Although electrical burns of the upper extremity comprise a small percentage of all thermal injuries, they present formidable clinical problems. The physician must not be lulled into a false sense of security because the visible cutaneous burn is not great. Sound surgical principles, such as the control of bacterial proliferation with topical chemotherapy, d\u00e9bridement of dead tissue, and timely wound closure, in conjunction with the expertise necessary in caring for thermally injured patients, are necessary for a maximally rehabilitated patient.", "contents": "Electrical injuries of the upper extremity. Although electrical burns of the upper extremity comprise a small percentage of all thermal injuries, they present formidable clinical problems. The physician must not be lulled into a false sense of security because the visible cutaneous burn is not great. Sound surgical principles, such as the control of bacterial proliferation with topical chemotherapy, d\u00e9bridement of dead tissue, and timely wound closure, in conjunction with the expertise necessary in caring for thermally injured patients, are necessary for a maximally rehabilitated patient."} {"id": "PMID:1256067", "title": "Cold injuries.", "content": "The management of patients with cold injuries of the hands may be extremely simple or relatively complex. The extent of the injury and the systemic response to the cold are the major influencing factors. In patients with extensive cold injuries, where all or a large portion of more than one extremity is cold or frozen and there has been a significant systemic response, treatment should be both systemic and local. Treatment should be directed toward both the preservation of tissue and maintenance of function of the damaged part. Minimal daily d\u00e9bridement and late amputation are important guidelines for care.", "contents": "Cold injuries. The management of patients with cold injuries of the hands may be extremely simple or relatively complex. The extent of the injury and the systemic response to the cold are the major influencing factors. In patients with extensive cold injuries, where all or a large portion of more than one extremity is cold or frozen and there has been a significant systemic response, treatment should be both systemic and local. Treatment should be directed toward both the preservation of tissue and maintenance of function of the damaged part. Minimal daily d\u00e9bridement and late amputation are important guidelines for care."} {"id": "PMID:1256068", "title": "The utilization of echocardiography in the differential diagnosis of cyanosis in the neonate.", "content": "Echocardiography is a useful and reliable tool for the clinical assessment of the cyanotic neonate. It can be applied rapidly without compromising even the critically ill neonate. Hypoplastic left and right heart syndromes can be diagnosed or excluded echocardiographically. The diagnostic exclusions of total anomalous pulmonary venous drainage and complete transposition of the great arteries in the neonate with cyanosis remain difficult challenges for the echocardiographer because of the variability of their anatomic and hemodynamic presentations.", "contents": "The utilization of echocardiography in the differential diagnosis of cyanosis in the neonate. Echocardiography is a useful and reliable tool for the clinical assessment of the cyanotic neonate. It can be applied rapidly without compromising even the critically ill neonate. Hypoplastic left and right heart syndromes can be diagnosed or excluded echocardiographically. The diagnostic exclusions of total anomalous pulmonary venous drainage and complete transposition of the great arteries in the neonate with cyanosis remain difficult challenges for the echocardiographer because of the variability of their anatomic and hemodynamic presentations."} {"id": "PMID:1256069", "title": "The pathogenesis and management of massive pulmonary hemorrhage in the neonate. Case report of a normal survivor.", "content": "A 1,760-G MALE INFANT SURVIVED MASSIVE PUlmonary hemorrhage. The literature is reviewed and the pathophysiologic changes and pathologic findings of this usually lethal complication of prematurity are discussed. Aggressive pulmonary toilet and ventilation seems warranted for these infants.", "contents": "The pathogenesis and management of massive pulmonary hemorrhage in the neonate. Case report of a normal survivor. A 1,760-G MALE INFANT SURVIVED MASSIVE PUlmonary hemorrhage. The literature is reviewed and the pathophysiologic changes and pathologic findings of this usually lethal complication of prematurity are discussed. Aggressive pulmonary toilet and ventilation seems warranted for these infants."} {"id": "PMID:1256070", "title": "Clinical observations on thyrotoxicosis coexisting with myotonic dystrophy.", "content": "Two cases are presented and a third is cited from the literature in which the onset of hyperthyroidism exacerbated acute weakness in previously undiagnosed myotonic dystrophy. In two of the cases a return to the euthyroid state after treatment was associated with marked clinical improvement in muscle weakness. In the third case, severe bulbar and respiratory muscle weakness, which was apparently aggravated by the thyrotoxicosis, was followed by aspiration pneumonitis and death. Possible mechanisms for the effect of excessive thyroxine on muscle function are reviewed. Early diagnosis and aggressive treatment of the hyperthyroidism is extremely important.", "contents": "Clinical observations on thyrotoxicosis coexisting with myotonic dystrophy. Two cases are presented and a third is cited from the literature in which the onset of hyperthyroidism exacerbated acute weakness in previously undiagnosed myotonic dystrophy. In two of the cases a return to the euthyroid state after treatment was associated with marked clinical improvement in muscle weakness. In the third case, severe bulbar and respiratory muscle weakness, which was apparently aggravated by the thyrotoxicosis, was followed by aspiration pneumonitis and death. Possible mechanisms for the effect of excessive thyroxine on muscle function are reviewed. Early diagnosis and aggressive treatment of the hyperthyroidism is extremely important."} {"id": "PMID:1256071", "title": "Chronic arterial insufficiency of the upper extremity.", "content": "When claudication or distal ischemia is significant, the treatment of choice for intrinsic arterial insufficiency of the upper extremity caused by atherosclerotic occlusive disease of the subclavian, axillary, or brachial artery with patent distal circulation is direct arterial surgery. Both endarterectomy and bypass procedures are utilized. In the 20 years from 1947 to 1967, 15 patients were operated on for such lesions and adequate circulation was restored in 12 patients treated by the direct method. Nine patients available for 1-year follow-up were cured of their symptoms; of the remaining three patients, one had amputation of an arm and two had sympathectomy with improvement. No hospital death occurred and morbidity was minimal. Although the diagnosis can be established on clinical grounds, arteriography is essential to ascertain the surgical procedure needed. Peripheral diseases involving the small arteries are clinically a more common cause of arterial insufficiency in the upper extremity; progress is slow and complications are infrequent. When ischemic complications exist, direct arterial surgery is not feasible and cervicodorsal sympathectomy is the usual form of treatment. Of 76 patients operated on for such disease, 74 underwent sympathetic neurectomy. The results were excellent, good, or satisfactory in 50 (78%) of the 64 traced patients. The remaining 14 patients had persistent or recurrent symptoms after operation. Removal of the stellate ganglion in addition to the second ganglion yielded better results and is indicated in recurrent or more cases.", "contents": "Chronic arterial insufficiency of the upper extremity. When claudication or distal ischemia is significant, the treatment of choice for intrinsic arterial insufficiency of the upper extremity caused by atherosclerotic occlusive disease of the subclavian, axillary, or brachial artery with patent distal circulation is direct arterial surgery. Both endarterectomy and bypass procedures are utilized. In the 20 years from 1947 to 1967, 15 patients were operated on for such lesions and adequate circulation was restored in 12 patients treated by the direct method. Nine patients available for 1-year follow-up were cured of their symptoms; of the remaining three patients, one had amputation of an arm and two had sympathectomy with improvement. No hospital death occurred and morbidity was minimal. Although the diagnosis can be established on clinical grounds, arteriography is essential to ascertain the surgical procedure needed. Peripheral diseases involving the small arteries are clinically a more common cause of arterial insufficiency in the upper extremity; progress is slow and complications are infrequent. When ischemic complications exist, direct arterial surgery is not feasible and cervicodorsal sympathectomy is the usual form of treatment. Of 76 patients operated on for such disease, 74 underwent sympathetic neurectomy. The results were excellent, good, or satisfactory in 50 (78%) of the 64 traced patients. The remaining 14 patients had persistent or recurrent symptoms after operation. Removal of the stellate ganglion in addition to the second ganglion yielded better results and is indicated in recurrent or more cases."} {"id": "PMID:1256105", "title": "The effect of prepaid group practice on physicians' utilization behavior.", "content": "The study is concerned with the practice of physicians in a prepaid group practice setting. Specifically, it is concerned 1) with investigating the extent of variation in physician behavior concerning use of clinical resources, that is, office visits and telephone calls, and technical resources, that is, x-rays and laboratory procedures, and 2) with determining the factors that account for such variation. The universe of this study consists of all internists practicing in 1970 in the prepaid group setting of Kaiser Permanente at Portland, Oregon, a total of 34. The overall framework for the study is based on the belief that medical training and the setting in which physicians work are significant determinants of their use of clinical and technical resources in different disease situations. Specifically, the framework posits that different sets of organizational variables are important in determining use of resources for acute and undiagnosed conditions. The findings reported in the study suggest that while the teaching environment in which a physician is trained is important in shaping his clinical personality, the setting in which he actually works contains its own source of influence over his professional activity. These results also provide supportive evidence for the widely held notion that prepaid group practice, through changing the nature of the incentives to physicians and introducing professional regulation, leads to a more efficient way of providing medical care by reducing the use of costly resources.", "contents": "The effect of prepaid group practice on physicians' utilization behavior. The study is concerned with the practice of physicians in a prepaid group practice setting. Specifically, it is concerned 1) with investigating the extent of variation in physician behavior concerning use of clinical resources, that is, office visits and telephone calls, and technical resources, that is, x-rays and laboratory procedures, and 2) with determining the factors that account for such variation. The universe of this study consists of all internists practicing in 1970 in the prepaid group setting of Kaiser Permanente at Portland, Oregon, a total of 34. The overall framework for the study is based on the belief that medical training and the setting in which physicians work are significant determinants of their use of clinical and technical resources in different disease situations. Specifically, the framework posits that different sets of organizational variables are important in determining use of resources for acute and undiagnosed conditions. The findings reported in the study suggest that while the teaching environment in which a physician is trained is important in shaping his clinical personality, the setting in which he actually works contains its own source of influence over his professional activity. These results also provide supportive evidence for the widely held notion that prepaid group practice, through changing the nature of the incentives to physicians and introducing professional regulation, leads to a more efficient way of providing medical care by reducing the use of costly resources."} {"id": "PMID:1256106", "title": "The clinical trial as a means for organizational change: report of a case study.", "content": "An attempt was made to introduce an innovation (nurse practitioners) into an organization (an outpatient clinic) using the format of a clinical trial. Staff physicians evaluated patients as to their acceptability for care by nurse practitioners before and after a 12-month trial. \"Acceptable\" patients were randomly assigned to control (regular clinic) and experimental groups (nurse practitioner care). There was a statistically significant increase (p less than 0.001) in physicians' willingness to delegate patients to nurse practitioners for care after the trial. Initial assessments of \"acceptable\" were highly associated with demographic variables such as age, race, and level of education. Patients' medical status, rather than personal characteristics, were found to be associated with decision making on re-evaluation. Positions were created for nurse practitioners on the staff of the clinic at the end of the experiment.", "contents": "The clinical trial as a means for organizational change: report of a case study. An attempt was made to introduce an innovation (nurse practitioners) into an organization (an outpatient clinic) using the format of a clinical trial. Staff physicians evaluated patients as to their acceptability for care by nurse practitioners before and after a 12-month trial. \"Acceptable\" patients were randomly assigned to control (regular clinic) and experimental groups (nurse practitioner care). There was a statistically significant increase (p less than 0.001) in physicians' willingness to delegate patients to nurse practitioners for care after the trial. Initial assessments of \"acceptable\" were highly associated with demographic variables such as age, race, and level of education. Patients' medical status, rather than personal characteristics, were found to be associated with decision making on re-evaluation. Positions were created for nurse practitioners on the staff of the clinic at the end of the experiment."} {"id": "PMID:1256107", "title": "The Sickness Impact Profile: reliability of a health status measure.", "content": "This report describes the results of research conducted on the reliability of the Sickness Impact Profile (SIP). The SIP is a questionnaire instrument designed to measure sickness-related behavioral dysfunction and is being developed for use as an outcome measure in the evaluation of health care. The test-retest reliability of the SIP in terms of several reliability measures was investigated using different interviewers, forms, administration procedures, and a variety of subjects who differed in terms of type and severity of dysfunction. The results provided evidence for the feasibility of collecting reliable data using the SIP under these various conditions. In addition, subject variability in relation to reliability is discussed.", "contents": "The Sickness Impact Profile: reliability of a health status measure. This report describes the results of research conducted on the reliability of the Sickness Impact Profile (SIP). The SIP is a questionnaire instrument designed to measure sickness-related behavioral dysfunction and is being developed for use as an outcome measure in the evaluation of health care. The test-retest reliability of the SIP in terms of several reliability measures was investigated using different interviewers, forms, administration procedures, and a variety of subjects who differed in terms of type and severity of dysfunction. The results provided evidence for the feasibility of collecting reliable data using the SIP under these various conditions. In addition, subject variability in relation to reliability is discussed."} {"id": "PMID:1256108", "title": "Drug information for prescribers and dispensers: toward a model system.", "content": "Four alternative ways of providing health care professionals with drug information are examined in terms of medical and social values. It is assumed that maximum patient benefit will result when prescribing decisions can be made in an environment of enlightened neutrality. The alternative of maintaining the status quo is discarded because it does little to provide practitioners with complete data. The second alternative notes major reforms that would further regulate promotional efforts and upgrade the qualifications of detailmen. Because this approach yields a suboptimum solution, a third alternative introduces the concept of a National Drug Education Foundation. This countervailing force would disseminate objective drug information to clinicians through 2,000 therapeutic consultants, subsidize professional journals and schools, develop regional drug information centers, and conduct a variety of related functions. Foundation operations are estimated to cost $167 million per year or about one-seventh of current expenditures for drug promotion and information. Since commercial inputs would not only be redundant but also tend to negate Foundation efforts, the fourth model contends that social benefits can be optimized only when such outlays are terminated.", "contents": "Drug information for prescribers and dispensers: toward a model system. Four alternative ways of providing health care professionals with drug information are examined in terms of medical and social values. It is assumed that maximum patient benefit will result when prescribing decisions can be made in an environment of enlightened neutrality. The alternative of maintaining the status quo is discarded because it does little to provide practitioners with complete data. The second alternative notes major reforms that would further regulate promotional efforts and upgrade the qualifications of detailmen. Because this approach yields a suboptimum solution, a third alternative introduces the concept of a National Drug Education Foundation. This countervailing force would disseminate objective drug information to clinicians through 2,000 therapeutic consultants, subsidize professional journals and schools, develop regional drug information centers, and conduct a variety of related functions. Foundation operations are estimated to cost $167 million per year or about one-seventh of current expenditures for drug promotion and information. Since commercial inputs would not only be redundant but also tend to negate Foundation efforts, the fourth model contends that social benefits can be optimized only when such outlays are terminated."} {"id": "PMID:1256109", "title": "Continuing education activities of physicians in solo and group practice: report on a pilot study.", "content": "Group practice has often been suggested as a form of medical care organization that facilitates professional pursuits, including continuing medical education. A survey was conducted among Iowa physicians in fee-for service multispecialty group practice and in other forms of fee-for-service medical practice, including solo practice and small partnerships to determine their levels of engagement in a number of different types of continuing medical education activities. While several differences between the two groups were found, the survey indicated that overall the levels of engagement for the two groups were similar.", "contents": "Continuing education activities of physicians in solo and group practice: report on a pilot study. Group practice has often been suggested as a form of medical care organization that facilitates professional pursuits, including continuing medical education. A survey was conducted among Iowa physicians in fee-for service multispecialty group practice and in other forms of fee-for-service medical practice, including solo practice and small partnerships to determine their levels of engagement in a number of different types of continuing medical education activities. While several differences between the two groups were found, the survey indicated that overall the levels of engagement for the two groups were similar."} {"id": "PMID:1256110", "title": "Evaluation of a cardiopulmonary resuscitation course for secondary schools retention study.", "content": "A retention study was implemented in Marshfield, Massachusetts in May 1974 in order to ascertain if cardiopulmonary resuscitation (CPR) skills could be retained by secondary school students who had 15 months previously received training in mouth to mouth resuscitation and cardiac compression. The retention study also addressed itself to the question whether a 28-minute \"refresher\" film on CPR skills prior to the test would serve to improve performance of CPR skills. (In the initial study, the students had been divided into two groups: those that received both didactic and practice sessions and those who received didactic training only.) All the initial practice group students (178 students who had received both didactic and practical CPR training) were divided equally into \"film\" and \"no film\" groups. A small sample of students (38) who had initially learned CPR skills from didactic materials only were also tested. These students were also divided into \"film\" and \"no film\" groups. Retention of continuous CPR skills, breaths anc compressions, showed very little loss. Retention of discrete CPR skills which included checking for breathing, opening the airway by tilting the head and lifting the neck, giving three quick breaths, feeling the pulse, and examining the pupil showed considerable loss of learning overtime. The film intervention did little to improve performance of CPR skills. No significant differences in performance were observed between \"film\" and \"no film\" groups. The findings of this study with respect to retention of continuous and discrete psychomotor sills closely parallel findings of the three-month retention study. In summary, this study would indicate that training of secondary students in CPR leads to good retention of essential skills. As indicated in the previous study, retention of the ancillary decision-making skills was not satisfactory. Methods for teaching these skills so that they will be retained over time need further development.", "contents": "Evaluation of a cardiopulmonary resuscitation course for secondary schools retention study. A retention study was implemented in Marshfield, Massachusetts in May 1974 in order to ascertain if cardiopulmonary resuscitation (CPR) skills could be retained by secondary school students who had 15 months previously received training in mouth to mouth resuscitation and cardiac compression. The retention study also addressed itself to the question whether a 28-minute \"refresher\" film on CPR skills prior to the test would serve to improve performance of CPR skills. (In the initial study, the students had been divided into two groups: those that received both didactic and practice sessions and those who received didactic training only.) All the initial practice group students (178 students who had received both didactic and practical CPR training) were divided equally into \"film\" and \"no film\" groups. A small sample of students (38) who had initially learned CPR skills from didactic materials only were also tested. These students were also divided into \"film\" and \"no film\" groups. Retention of continuous CPR skills, breaths anc compressions, showed very little loss. Retention of discrete CPR skills which included checking for breathing, opening the airway by tilting the head and lifting the neck, giving three quick breaths, feeling the pulse, and examining the pupil showed considerable loss of learning overtime. The film intervention did little to improve performance of CPR skills. No significant differences in performance were observed between \"film\" and \"no film\" groups. The findings of this study with respect to retention of continuous and discrete psychomotor sills closely parallel findings of the three-month retention study. In summary, this study would indicate that training of secondary students in CPR leads to good retention of essential skills. As indicated in the previous study, retention of the ancillary decision-making skills was not satisfactory. Methods for teaching these skills so that they will be retained over time need further development."} {"id": "PMID:1256111", "title": "The role of new health practitioners in a prepaid group practice: changes in the distribution of ambulatory care between physician and nonphysician providers of care.", "content": "Changes in the distribution of ambulatory care between physicians and new health practitioners (NHP) are examined in the pediatric and adult medicine departments of a prepaid group practice program. The study covers a three-year period during which NHP were extensively introduced to provide a broad range of ambulatory care. The source of data is a routine data information system that utilizes an encounter form to capture a minimal data set on every patient visit, including the provider's statement of diagnosis. Based on these data, changes in staffing are related to changes in workload and content of practice of both physicians and NHP.", "contents": "The role of new health practitioners in a prepaid group practice: changes in the distribution of ambulatory care between physician and nonphysician providers of care. Changes in the distribution of ambulatory care between physicians and new health practitioners (NHP) are examined in the pediatric and adult medicine departments of a prepaid group practice program. The study covers a three-year period during which NHP were extensively introduced to provide a broad range of ambulatory care. The source of data is a routine data information system that utilizes an encounter form to capture a minimal data set on every patient visit, including the provider's statement of diagnosis. Based on these data, changes in staffing are related to changes in workload and content of practice of both physicians and NHP."} {"id": "PMID:1256112", "title": "Electrophysiologic properties of antidysrhythmic drugs as a rational basis for therapy.", "content": "The often emergent nature of life-threatening cardiac dysrhythmias, the frequent seeming \"resistance\" of the abnormal heart rhythm to therapy, and the commonly encountered toxicity of antidysrhythmic agents combine to make treatment of cardiac dysrhythmias one of the strictest challenges to the practicing physician. Although electrophysiologic studies have markedly increased out understanding of dysrhythmogenesis and the actions of anti-dysrhythmic drugs, these numerous investigations have provided but little assistance to the practicing physician either as an intellectual framework or as a guide to patient care. The electrophysiologic classification of the antidysrhythmic drugs presented in this paper should be acceptable both to the electrophysiologist and the clinician since it is based on alterations in basic membrane properties and correlates well with clinical realities. It serves as a guide to initial drug selection, anticipated bioelectric complications, the use of alternative drugs, and combination antidysrhythmic therapy.", "contents": "Electrophysiologic properties of antidysrhythmic drugs as a rational basis for therapy. The often emergent nature of life-threatening cardiac dysrhythmias, the frequent seeming \"resistance\" of the abnormal heart rhythm to therapy, and the commonly encountered toxicity of antidysrhythmic agents combine to make treatment of cardiac dysrhythmias one of the strictest challenges to the practicing physician. Although electrophysiologic studies have markedly increased out understanding of dysrhythmogenesis and the actions of anti-dysrhythmic drugs, these numerous investigations have provided but little assistance to the practicing physician either as an intellectual framework or as a guide to patient care. The electrophysiologic classification of the antidysrhythmic drugs presented in this paper should be acceptable both to the electrophysiologist and the clinician since it is based on alterations in basic membrane properties and correlates well with clinical realities. It serves as a guide to initial drug selection, anticipated bioelectric complications, the use of alternative drugs, and combination antidysrhythmic therapy."} {"id": "PMID:1256113", "title": "A rapid response system for out-of-hospital cardiac emergencies.", "content": "We have reviewed several aspects of our initial 5 years' experience with an out-of-hospital emergency medical care system. This system is stratified and provides for rapid primary response and, when indicated, secondary response by specially trained paramedical personnel. Patient care is physician-supervised and closely monitored. Although considerable attention has been directed to acute complications of ischemic heart disease, particularly the problem of sudden cardiac death, the system is broadly based and responds to all medical emergencies. We are impressed with the ability of nonphysicians to acquire certain medical skills and judgment. Indeed, the effectiveness of this system is largely dependent on paramedical personnel. Such systems of prehospital emergency medical care will probably have an impact greater than that of hospital coronary care units in reducing the mortality from ischemic heart disease.", "contents": "A rapid response system for out-of-hospital cardiac emergencies. We have reviewed several aspects of our initial 5 years' experience with an out-of-hospital emergency medical care system. This system is stratified and provides for rapid primary response and, when indicated, secondary response by specially trained paramedical personnel. Patient care is physician-supervised and closely monitored. Although considerable attention has been directed to acute complications of ischemic heart disease, particularly the problem of sudden cardiac death, the system is broadly based and responds to all medical emergencies. We are impressed with the ability of nonphysicians to acquire certain medical skills and judgment. Indeed, the effectiveness of this system is largely dependent on paramedical personnel. Such systems of prehospital emergency medical care will probably have an impact greater than that of hospital coronary care units in reducing the mortality from ischemic heart disease."} {"id": "PMID:1256116", "title": "Tachycardias and electrical pacing.", "content": "Techniques of electrical pacing for the treatment of tachycardias are multiple. The choice of a suitable method for a particular tachycardia depends upon understanding the mechanism of the tachycardia and the pacing characteristics that will lead to interruption or suppression of the tachycardia, or to ventricular slowing. Electrical pacing is indicated for tachycardias when drug therapy alone has failed or cannot be initiated or continued, and only for those tachycardias that are likely to respond to this type of electrical stimulation. In either the circus movement type or the ectopic pacemaker type an ectopic tachycardia is more likely to be suppressed if the pacing site is near the site of origin of the tachycardia. Pacing more rapidly than the basic rate in order to prevent or abolish tachycardias is termed overdrive suppression. The mechanisms responsible for this phenomenon may be associated with release of acetylcholine, release of potassium, activation of an electrogenic sodium pump, increase in cardiac output and coronary flow, decrease in size of the heart with a consequent decrease in wall tension, and decrease in the inhomogeneity of recovery of excitability that occurs at more rapid rates in the non-ischemic heart. All of these effects of pacing suppress accelerated pacemaker activity or prevent emergence of conditions favorable for development of circus movement tachycardias. Paired, coupled, or rapid atrial pacing may improve ventricular performance or slow ventricular rate, or both, without abolishing the ectopic pacemaker activity. Atrial pacing with pacing sites located at endocardial, epicardial, coronary sinus, trans-septal, or esophageal locations may interrupt or prevent rapid supraventricular or ventricular arrhythmias. Similarly, ventricular pacing at endocardial, epicardial, myocardial, or transthoracic sites may be equally effective. Artificial pacing has abolished almost every type of tachycardia. Ventricular fibrillation always, and atrial fibrillation usually, require countershock if electrical treatment is to be employed, although defibrillation of the atria by rapid pacing has been reported once. Unipolar or bipolar pacemakers may be used temporarily, or permanently after implantation. Pacing rates used to abolish supraventricular tachycardias range from single premature beats to alternating current atrial pacing at 3600 cycles per minute. Artificial electrical stimulation of the heart may be on demand, or may be competitive (fixed rate). External magnets, induction coil coupling, and radio frequency signals allow competitive pacing to be used intermittently, with permanently implanted pacemakers. Thus, electrical pacing of the heart is a technique of major importance for the control of rapid heart rates.", "contents": "Tachycardias and electrical pacing. Techniques of electrical pacing for the treatment of tachycardias are multiple. The choice of a suitable method for a particular tachycardia depends upon understanding the mechanism of the tachycardia and the pacing characteristics that will lead to interruption or suppression of the tachycardia, or to ventricular slowing. Electrical pacing is indicated for tachycardias when drug therapy alone has failed or cannot be initiated or continued, and only for those tachycardias that are likely to respond to this type of electrical stimulation. In either the circus movement type or the ectopic pacemaker type an ectopic tachycardia is more likely to be suppressed if the pacing site is near the site of origin of the tachycardia. Pacing more rapidly than the basic rate in order to prevent or abolish tachycardias is termed overdrive suppression. The mechanisms responsible for this phenomenon may be associated with release of acetylcholine, release of potassium, activation of an electrogenic sodium pump, increase in cardiac output and coronary flow, decrease in size of the heart with a consequent decrease in wall tension, and decrease in the inhomogeneity of recovery of excitability that occurs at more rapid rates in the non-ischemic heart. All of these effects of pacing suppress accelerated pacemaker activity or prevent emergence of conditions favorable for development of circus movement tachycardias. Paired, coupled, or rapid atrial pacing may improve ventricular performance or slow ventricular rate, or both, without abolishing the ectopic pacemaker activity. Atrial pacing with pacing sites located at endocardial, epicardial, coronary sinus, trans-septal, or esophageal locations may interrupt or prevent rapid supraventricular or ventricular arrhythmias. Similarly, ventricular pacing at endocardial, epicardial, myocardial, or transthoracic sites may be equally effective. Artificial pacing has abolished almost every type of tachycardia. Ventricular fibrillation always, and atrial fibrillation usually, require countershock if electrical treatment is to be employed, although defibrillation of the atria by rapid pacing has been reported once. Unipolar or bipolar pacemakers may be used temporarily, or permanently after implantation. Pacing rates used to abolish supraventricular tachycardias range from single premature beats to alternating current atrial pacing at 3600 cycles per minute. Artificial electrical stimulation of the heart may be on demand, or may be competitive (fixed rate). External magnets, induction coil coupling, and radio frequency signals allow competitive pacing to be used intermittently, with permanently implanted pacemakers. Thus, electrical pacing of the heart is a technique of major importance for the control of rapid heart rates."} {"id": "PMID:1256190", "title": "Symposium: management of tumors of the parotid gland.", "content": "The successful management of swellings in the parotid gland region is dependent upon the establishment of a clinical and/or histologic diagnosis of the condition responsible for the production of the abnormal swelling. All mobile parotid tumors are removed as an excisional biopsy with preservation of the facial nerve. A preoperative biopsy will not influence the subsequent management of these lesions. An aspiration biopsy is employed to evaluate all primary, previously undiagnosed, non-ulcerative parotid tumors suspected of being clinically malignant. An experienced pathologist views with confidence evaluation of solid material that has been carefully separated from the aspirated specimen. It is our opinion that when the biopsy tract is removed with the tumor, there is less risk of surgical wound contamination by tumor than when there is an incisional biopsy or incomplete excision of the tumor for frozen or permanent section diagnosis. One should not expect to derive as much information from an aspiration biopsy as may be derived from a formal incisional biopsy. If the histologic interpretation of the aspirated material is inconclusive, one may proceed to accept the added risk of an open biopsy. If it is known preoperatively that the tumor is malignant, that it is other than a low grade cancer, and that the tumor should be treated surgically, management of the facial nerve and the cervical nodes may be anticipated. This may be accomplished by an aspiration biopsy.", "contents": "Symposium: management of tumors of the parotid gland. The successful management of swellings in the parotid gland region is dependent upon the establishment of a clinical and/or histologic diagnosis of the condition responsible for the production of the abnormal swelling. All mobile parotid tumors are removed as an excisional biopsy with preservation of the facial nerve. A preoperative biopsy will not influence the subsequent management of these lesions. An aspiration biopsy is employed to evaluate all primary, previously undiagnosed, non-ulcerative parotid tumors suspected of being clinically malignant. An experienced pathologist views with confidence evaluation of solid material that has been carefully separated from the aspirated specimen. It is our opinion that when the biopsy tract is removed with the tumor, there is less risk of surgical wound contamination by tumor than when there is an incisional biopsy or incomplete excision of the tumor for frozen or permanent section diagnosis. One should not expect to derive as much information from an aspiration biopsy as may be derived from a formal incisional biopsy. If the histologic interpretation of the aspirated material is inconclusive, one may proceed to accept the added risk of an open biopsy. If it is known preoperatively that the tumor is malignant, that it is other than a low grade cancer, and that the tumor should be treated surgically, management of the facial nerve and the cervical nodes may be anticipated. This may be accomplished by an aspiration biopsy."} {"id": "PMID:1256191", "title": "Symposium: management of tumors of the parotid gland. III. Management of the facial nerve.", "content": "The facial nerve is protected in parotid surgery by finding the main trunk first and peripherally dissecting free the branches. The most constant landmark is the groove between the mastoid and the bony ear canal. Wide exposure of this groove should be obtained without \"tunnelling.\" The thick (2-3 mm) white trunk is dissected forward using the electric stimulator before cutting parotid tissue. Nerve injury is more common in the peripheral branches. Nerve location in recurrent parotid tumors is more difficult. The main trunk may be found more posteriorly than in the previous surgery, but often peripheral branches must be identified crossing the masseter, facial vessels, or the parotid duct; retrograde dissection to the trunk follows. For proven invading malignancy, the trunk or branches may be sacrificed, but immediate grafting should be attempted usually with the greater auricular nerve.", "contents": "Symposium: management of tumors of the parotid gland. III. Management of the facial nerve. The facial nerve is protected in parotid surgery by finding the main trunk first and peripherally dissecting free the branches. The most constant landmark is the groove between the mastoid and the bony ear canal. Wide exposure of this groove should be obtained without \"tunnelling.\" The thick (2-3 mm) white trunk is dissected forward using the electric stimulator before cutting parotid tissue. Nerve injury is more common in the peripheral branches. Nerve location in recurrent parotid tumors is more difficult. The main trunk may be found more posteriorly than in the previous surgery, but often peripheral branches must be identified crossing the masseter, facial vessels, or the parotid duct; retrograde dissection to the trunk follows. For proven invading malignancy, the trunk or branches may be sacrificed, but immediate grafting should be attempted usually with the greater auricular nerve."} {"id": "PMID:1256192", "title": "Surgical elimination of drooling.", "content": "Drooling involves great practical problems in the care of patients with cerebral paralysis and mental deficiency. Different types of medical and surgical treatments have been used. In 17 disabled patients chorda tympani has been cut bilaterally in order to reduce the production of saliva, especially from the submandibular and sublingual glands. The loss of taste on the anterior part of the tongue seems to contribute to the reduction of salivation. Fifteen patients have been observed postoperatively during two to four years. Five patients have been cured, two are considerably improved and seven partially improved. The effect of nerve section was illustrated by Tcm99 scintigraphy in two additional cases before operation and six months postoperatively. No complications were observed.", "contents": "Surgical elimination of drooling. Drooling involves great practical problems in the care of patients with cerebral paralysis and mental deficiency. Different types of medical and surgical treatments have been used. In 17 disabled patients chorda tympani has been cut bilaterally in order to reduce the production of saliva, especially from the submandibular and sublingual glands. The loss of taste on the anterior part of the tongue seems to contribute to the reduction of salivation. Fifteen patients have been observed postoperatively during two to four years. Five patients have been cured, two are considerably improved and seven partially improved. The effect of nerve section was illustrated by Tcm99 scintigraphy in two additional cases before operation and six months postoperatively. No complications were observed."} {"id": "PMID:1256193", "title": "Fibrosarcoma of the head and neck in children.", "content": "A retrospective study of 11 children with fibrosarcoma of the head and neck is presented. Six of these tumors are well differentiated, and three are poorly differentiated. Nine patients were followed for over six years and are available for treatment evaluation. The results of treatment indicate that patients with superficially located, well differentiated tumors occurring at sites where wide surgical margins can be obtained have the most favorable prognosis.", "contents": "Fibrosarcoma of the head and neck in children. A retrospective study of 11 children with fibrosarcoma of the head and neck is presented. Six of these tumors are well differentiated, and three are poorly differentiated. Nine patients were followed for over six years and are available for treatment evaluation. The results of treatment indicate that patients with superficially located, well differentiated tumors occurring at sites where wide surgical margins can be obtained have the most favorable prognosis."} {"id": "PMID:1256195", "title": "Construction of a practical and inexpensive air stimulator for caloric vestibular testing.", "content": "An inexpensive and practical method for delivering air into the aural canal at a selected stable temperature is described. A water-air heat exchanger utilizing the external circulation of a constant-temperature water bath brings the temperature of the air stream to a chosen value. Measurements indicate stable air outflow temperatures are maintained when proper nozzle design and air flow rates are employed. The apparatus is easy to construct and has proven convenient and effective when used in the clinical vestibular laboratory.", "contents": "Construction of a practical and inexpensive air stimulator for caloric vestibular testing. An inexpensive and practical method for delivering air into the aural canal at a selected stable temperature is described. A water-air heat exchanger utilizing the external circulation of a constant-temperature water bath brings the temperature of the air stream to a chosen value. Measurements indicate stable air outflow temperatures are maintained when proper nozzle design and air flow rates are employed. The apparatus is easy to construct and has proven convenient and effective when used in the clinical vestibular laboratory."} {"id": "PMID:1256196", "title": "Effects of anoxia and ethacrynic acid upon ampullar endolymphatic potential and upon high energy phosphates in ampullar wall.", "content": "The ampullar endolymphatic potential (AEP) was studied in the guinea pig during ischemia and asphyxia and following systemic application of ethacrynic acid. In addition the specialized and nonspecialized portions of the ampullar wall were analyzed for ATP and P-creatine at different conditions of metabolic interference. Under control conditions the AEP amounted to + 4.6 +/- 1.2 mV. In both types of hypoxia the decline of the AEP proceeded on a much slower time scale than that of the cochlear endolymphatic potential (CEP), and the maximum negativity reached was considerably less. Quantitative analysis of both types of ampullar wall tissue indicated a much slower decline in hypoxia of ATP levels than in the stria vascularis. Changes in P-creatine levels were considerably more rapid. The AEP became reduced and changed polarity also by intoxication with ethacrynic acid (EA), but higher dosages (above 70 mg/kg) were necessary than for effects upon the CEP and much longer time periods were required for attainment of maximum negativity. The maximum negativity of the AEP was significantly greater at a dosage of 100 mg/kg of EA than during ischemia. At the point of maximum depression of the AEP P-creatine levels in both types of ampullar tissue were unchanged, but ATP levels were significantly reduced in the specialized portions of ampullar wall.", "contents": "Effects of anoxia and ethacrynic acid upon ampullar endolymphatic potential and upon high energy phosphates in ampullar wall. The ampullar endolymphatic potential (AEP) was studied in the guinea pig during ischemia and asphyxia and following systemic application of ethacrynic acid. In addition the specialized and nonspecialized portions of the ampullar wall were analyzed for ATP and P-creatine at different conditions of metabolic interference. Under control conditions the AEP amounted to + 4.6 +/- 1.2 mV. In both types of hypoxia the decline of the AEP proceeded on a much slower time scale than that of the cochlear endolymphatic potential (CEP), and the maximum negativity reached was considerably less. Quantitative analysis of both types of ampullar wall tissue indicated a much slower decline in hypoxia of ATP levels than in the stria vascularis. Changes in P-creatine levels were considerably more rapid. The AEP became reduced and changed polarity also by intoxication with ethacrynic acid (EA), but higher dosages (above 70 mg/kg) were necessary than for effects upon the CEP and much longer time periods were required for attainment of maximum negativity. The maximum negativity of the AEP was significantly greater at a dosage of 100 mg/kg of EA than during ischemia. At the point of maximum depression of the AEP P-creatine levels in both types of ampullar tissue were unchanged, but ATP levels were significantly reduced in the specialized portions of ampullar wall."} {"id": "PMID:1256194", "title": "Mondini defect in association with multiple congenital anomalies.", "content": "A case of bilaterally symmetrical genetic aplasia conforming to Mondini type of congenital deformity in a 12-day-old child is presented with the help of temporal bone sections. Cochlear changes include a stunted modiolus, deficient interscalar septum between the middle and upper coils forming a scala communis cochleae, a degenerated organ of Corti and reduced spiral ganglion cells and dendrites. The vestibule is malformed, with membranous labyrinth being deficient. The utricle and semicircular canals are absent. There is no oval window or stapedial footplate, and the facial nerve is hypoplastic. An interesting feature is the unusual association of bilateral bony choanal atresia, atrial septal defect, cleft lip, absence of olfactory bulbs in the brain, and congenital ophthalmic anomalies.", "contents": "Mondini defect in association with multiple congenital anomalies. A case of bilaterally symmetrical genetic aplasia conforming to Mondini type of congenital deformity in a 12-day-old child is presented with the help of temporal bone sections. Cochlear changes include a stunted modiolus, deficient interscalar septum between the middle and upper coils forming a scala communis cochleae, a degenerated organ of Corti and reduced spiral ganglion cells and dendrites. The vestibule is malformed, with membranous labyrinth being deficient. The utricle and semicircular canals are absent. There is no oval window or stapedial footplate, and the facial nerve is hypoplastic. An interesting feature is the unusual association of bilateral bony choanal atresia, atrial septal defect, cleft lip, absence of olfactory bulbs in the brain, and congenital ophthalmic anomalies."} {"id": "PMID:1256198", "title": "Symposium: management of tumors of the parotid gland. II. Diagnosis of parotid gland swelling.", "content": "Diagnosis of parotid gland swellings can be approached by attempting to answer the following questions: 1. Is it parotid? 2. Is it inflammatory or neoplastic? 3. If it is neoplastic, is it benign or malignant? Diagnosis is made by following the classical physical diagnostic procedures of inspection, palpation, and auscultation. These are followed by radiographic procedures, such as plain films, sialography and technetium scanning. Since approximately one in four parotid neoplasms is malignant, a definitive step should be biopsy. Excisional biopsy is recommended.", "contents": "Symposium: management of tumors of the parotid gland. II. Diagnosis of parotid gland swelling. Diagnosis of parotid gland swellings can be approached by attempting to answer the following questions: 1. Is it parotid? 2. Is it inflammatory or neoplastic? 3. If it is neoplastic, is it benign or malignant? Diagnosis is made by following the classical physical diagnostic procedures of inspection, palpation, and auscultation. These are followed by radiographic procedures, such as plain films, sialography and technetium scanning. Since approximately one in four parotid neoplasms is malignant, a definitive step should be biopsy. Excisional biopsy is recommended."} {"id": "PMID:1256199", "title": "Symposium: management of tumors of the parotid gland. IV. Differential diagnosis and management of deep lobe parotid tumors.", "content": "The problem of the pathological anatomy, the diagnosis, differential diagnosis and management of tumors of the parapharyngeal space has been discussed. Preoperative biopsy is to be discouraged in all benign lesions of the area. External approach with good adequate exposure is most important. Surgery is the treatment of choice in the benign lesion, by far the most common tumor as reported in the literature. Any tumor or disease of the superficial parotid may also be found in the deep lobe.", "contents": "Symposium: management of tumors of the parotid gland. IV. Differential diagnosis and management of deep lobe parotid tumors. The problem of the pathological anatomy, the diagnosis, differential diagnosis and management of tumors of the parapharyngeal space has been discussed. Preoperative biopsy is to be discouraged in all benign lesions of the area. External approach with good adequate exposure is most important. Surgery is the treatment of choice in the benign lesion, by far the most common tumor as reported in the literature. Any tumor or disease of the superficial parotid may also be found in the deep lobe."} {"id": "PMID:1256201", "title": "Symposium: the supra-tip in rhinoplasty: a dilemma. I. Theories and causes of supra-tip convexities.", "content": "Supratip convexities following rhinoplasty present a challenge to the surgeon. The correct diagnosis as to cause is necessary for proper correction. The pertinent anatomy of this area -- the theories, causes, suggested methods of prevention and correction -- are presented.", "contents": "Symposium: the supra-tip in rhinoplasty: a dilemma. I. Theories and causes of supra-tip convexities. Supratip convexities following rhinoplasty present a challenge to the surgeon. The correct diagnosis as to cause is necessary for proper correction. The pertinent anatomy of this area -- the theories, causes, suggested methods of prevention and correction -- are presented."} {"id": "PMID:1256202", "title": "Symposium: the supra-tip in rhinoplasty: a dilemma. II. Influence of surrounding structure and prevention.", "content": "One of the most annoying complications of rhinoplasty is the supra-tip hump (pollybeak). Possible causes are failure to surgically compensate for: 1. The increased skin thickness above the tip. 2. Supra-tip keloid tendency. 3. Overactive depressor septi muscles. 4. Loss of natural tip support by the upper lateral cartilages and septum.", "contents": "Symposium: the supra-tip in rhinoplasty: a dilemma. II. Influence of surrounding structure and prevention. One of the most annoying complications of rhinoplasty is the supra-tip hump (pollybeak). Possible causes are failure to surgically compensate for: 1. The increased skin thickness above the tip. 2. Supra-tip keloid tendency. 3. Overactive depressor septi muscles. 4. Loss of natural tip support by the upper lateral cartilages and septum."} {"id": "PMID:1256203", "title": "Symposium: the supra-tip in rhinoplasty: a dilemma. III. Supra-tip soft-tissue rounding after rhinoplasty: causes, prevention and treatment.", "content": "1. During rhinoplasty the surgeon can easily set in motion changes which produce soft-tissue rounding of the supra-tip area postoperatively. 2. Preventive as well as therapeutic measures are discussed.", "contents": "Symposium: the supra-tip in rhinoplasty: a dilemma. III. Supra-tip soft-tissue rounding after rhinoplasty: causes, prevention and treatment. 1. During rhinoplasty the surgeon can easily set in motion changes which produce soft-tissue rounding of the supra-tip area postoperatively. 2. Preventive as well as therapeutic measures are discussed."} {"id": "PMID:1256205", "title": "Symposium: contraindications to tympanoplasty. II. An exercise in clinical judgment.", "content": "The two primary symptoms of chronic ear disease are otorrhea and hearing loss. The goal of any tympanoplasty is to eradicate disease and improve hearing. These are the primary indications for this procedure. The success or failure of the surgery is influenced by many factors such as the age and general health of the patient, the extent and type of disease present, and whether the upper airway is functioning properly. Contraindications to tympanoplasty will vary from one surgeon to another depending upon his training, philosophy, experience, and surgical skill. It is helpful to think of these contraindications as being either absolute or relative. Absolute contraindications consist of: 1. uncontrolled cholesteatoma; 2. malignant tumors; 3. unusual infections and/or extenuating circumstances; and 4. complications of chronic ear disease, such as meningitis, brain abscess, or lateral sinus thrombosis. Relative contraindications are less well defined: 1. eustachian tube insufficiency or non-function; 2. the uncooperative patient; 3. the dead ear; 4. the better hearing or only hearing ear; 5. the elderly patient; 6. the young child; and 7. the repeated failure case. The otologic surgeon must exercise good clinical judgment in selecting patients for tympanoplasty. This paper deals with some of the more common problems in decision making.", "contents": "Symposium: contraindications to tympanoplasty. II. An exercise in clinical judgment. The two primary symptoms of chronic ear disease are otorrhea and hearing loss. The goal of any tympanoplasty is to eradicate disease and improve hearing. These are the primary indications for this procedure. The success or failure of the surgery is influenced by many factors such as the age and general health of the patient, the extent and type of disease present, and whether the upper airway is functioning properly. Contraindications to tympanoplasty will vary from one surgeon to another depending upon his training, philosophy, experience, and surgical skill. It is helpful to think of these contraindications as being either absolute or relative. Absolute contraindications consist of: 1. uncontrolled cholesteatoma; 2. malignant tumors; 3. unusual infections and/or extenuating circumstances; and 4. complications of chronic ear disease, such as meningitis, brain abscess, or lateral sinus thrombosis. Relative contraindications are less well defined: 1. eustachian tube insufficiency or non-function; 2. the uncooperative patient; 3. the dead ear; 4. the better hearing or only hearing ear; 5. the elderly patient; 6. the young child; and 7. the repeated failure case. The otologic surgeon must exercise good clinical judgment in selecting patients for tympanoplasty. This paper deals with some of the more common problems in decision making."} {"id": "PMID:1256206", "title": "Symposium: contraindications to tympanoplasty. IV. Contraindications to tympanoplasty.", "content": "Aural and non-aural disorders that are relative or are absolute contraindications to tympanoplasty surgery are discussed. Particular attention is focused on non-aural convert general medical conditions that may escape the otologist's attention as he is not daily concerned in the management of such conditions. The aural contra-indications are dealt with briefly because of the obvious and well known disorders that are familiar to all otologists.", "contents": "Symposium: contraindications to tympanoplasty. IV. Contraindications to tympanoplasty. Aural and non-aural disorders that are relative or are absolute contraindications to tympanoplasty surgery are discussed. Particular attention is focused on non-aural convert general medical conditions that may escape the otologist's attention as he is not daily concerned in the management of such conditions. The aural contra-indications are dealt with briefly because of the obvious and well known disorders that are familiar to all otologists."} {"id": "PMID:1256207", "title": "Familial laryngomalacia: a case report.", "content": "This report describes the hereditary occurrence of severe laryngomalacia in three of five siblings of a Mexican-American family. The mother, who experienced respiratory difficulties in the first year of life, may also have been affected. All three affected children required neonatal tracheostomy, and two died of pulmonary complications. Histological studies of tracheal cartilage revealed distinct hypercellularity and histochemical staining abnormalities of the cartilaginous matrix without defects in skeletal cartilage. Although laryngomalacia is not uncommon, this disorder previously has not been documented to occur as a familial trait, nor have distinct abnormalities of cartilage been associated with laryngomalacia. This report suggests that etiologic and pathophysiologic heterogeniety exists for the clinical syndrome of laryngomalacia.", "contents": "Familial laryngomalacia: a case report. This report describes the hereditary occurrence of severe laryngomalacia in three of five siblings of a Mexican-American family. The mother, who experienced respiratory difficulties in the first year of life, may also have been affected. All three affected children required neonatal tracheostomy, and two died of pulmonary complications. Histological studies of tracheal cartilage revealed distinct hypercellularity and histochemical staining abnormalities of the cartilaginous matrix without defects in skeletal cartilage. Although laryngomalacia is not uncommon, this disorder previously has not been documented to occur as a familial trait, nor have distinct abnormalities of cartilage been associated with laryngomalacia. This report suggests that etiologic and pathophysiologic heterogeniety exists for the clinical syndrome of laryngomalacia."} {"id": "PMID:1256208", "title": "Ischemic paralysis of the facial nerve: a possible etiologic factor in Bell's palsy.", "content": "Numerous causes of peripheral facial nerve paralyses have been described; however, none has satisfactorily explained the genesis of the most common type of paralysis, Bell's palsy. Two patients undergoing an experimental embolization of vascular intracranial tumors suffered a total peripheral facial nerve paralysis when occlusion of the middle meningeal artery had been accomplished. It is speculated that this paralysis resulted from ischemia of the horizontal portion of the facial nerve, an observation that has not previously been described and that might be applicable as well to the etiology of Bell's palsy.", "contents": "Ischemic paralysis of the facial nerve: a possible etiologic factor in Bell's palsy. Numerous causes of peripheral facial nerve paralyses have been described; however, none has satisfactorily explained the genesis of the most common type of paralysis, Bell's palsy. Two patients undergoing an experimental embolization of vascular intracranial tumors suffered a total peripheral facial nerve paralysis when occlusion of the middle meningeal artery had been accomplished. It is speculated that this paralysis resulted from ischemia of the horizontal portion of the facial nerve, an observation that has not previously been described and that might be applicable as well to the etiology of Bell's palsy."} {"id": "PMID:1256209", "title": "Rhabdomyoma of the pharynx.", "content": "The occurrence of a large pharyngeal rhabdomyoma in an otherwise healthy adult male is discussed in this paper. This lesion, except for local symptomatology, is established as benign. A differential diagnosis, as well as the specific surgical approach to its removal, are also presented.", "contents": "Rhabdomyoma of the pharynx. The occurrence of a large pharyngeal rhabdomyoma in an otherwise healthy adult male is discussed in this paper. This lesion, except for local symptomatology, is established as benign. A differential diagnosis, as well as the specific surgical approach to its removal, are also presented."} {"id": "PMID:1256210", "title": "Tracheostomy in infants and young children.", "content": "Seventy-three tracheostomies performed in children three years of age and under in a 52-month period are discussed. Thirty-six were under one year of age. Forty-one were performed for upper airway obstruction, 23 for ventilation or suction, and nine for a combination of upper airway obstruction and lower bronchopulmonary disease. Operative complications developed in 10 patients, and postoperative complications in 16. The most common complication was interstitial air; the most deadly was obstruction of the cannula. There were 20 deaths. Sixteen were due to the patients' diseases; four were due to complications of tracheostomy. If serious operative and postoperative complications are avoided, the important factors determining prognosis are the patient's age and the condition for which the tracheostomy was done. The long term results in these patients show this to be true for both survival and duration of tracheostomy.", "contents": "Tracheostomy in infants and young children. Seventy-three tracheostomies performed in children three years of age and under in a 52-month period are discussed. Thirty-six were under one year of age. Forty-one were performed for upper airway obstruction, 23 for ventilation or suction, and nine for a combination of upper airway obstruction and lower bronchopulmonary disease. Operative complications developed in 10 patients, and postoperative complications in 16. The most common complication was interstitial air; the most deadly was obstruction of the cannula. There were 20 deaths. Sixteen were due to the patients' diseases; four were due to complications of tracheostomy. If serious operative and postoperative complications are avoided, the important factors determining prognosis are the patient's age and the condition for which the tracheostomy was done. The long term results in these patients show this to be true for both survival and duration of tracheostomy."} {"id": "PMID:1256211", "title": "Laryngeal suspension in head and neck surgery.", "content": "Nineteen cases with major resections of the head and neck were treated with laryngeal suspension and cricopharyngeal myotomy in an attempt to allow swallowing function postoperatively and avoid a total laryngectomy. Sixteen cases were available for evaluation. Eight cases (50%) were able to eat by mouth, 15 patients (94%) had a normal airway and 14 patients (87%) had intelligible speech.", "contents": "Laryngeal suspension in head and neck surgery. Nineteen cases with major resections of the head and neck were treated with laryngeal suspension and cricopharyngeal myotomy in an attempt to allow swallowing function postoperatively and avoid a total laryngectomy. Sixteen cases were available for evaluation. Eight cases (50%) were able to eat by mouth, 15 patients (94%) had a normal airway and 14 patients (87%) had intelligible speech."} {"id": "PMID:1256212", "title": "The cochlear implant; basic principles.", "content": "In recent years the cochlear implant has been a subject of much discussion and controversy. The clinician has often been confused by the conflicting reports of success and failure. In this paper the development of the cochlear implant is reviewed and its present status summarized. It is hoped that the clinician may thereby gain an understanding of this device so that he can better evaluate its present and future status. Selection of Patients for Cochlear Implantation. The cochlear implant will benefit only those patients with hair cell loss who have remaining viable auditory neurons. In order to determine whether viable neurons remain, an electric current is passed through a small needle which is place into the promontory through the tympanic membrane. If patients experience an auditory sensation as a result of this electrical stimulation, it is felt that they are suitable candidates for a cochlear implant. Feasibility of Long-Term VIIIth Nerve Stimulation. Many questions have been raised regarding the feasibility of long-term stimulation of the auditory nerve. The first question raised was whether the auditory nerve would survive severe hair cell degeneration. Studies have shown that in most cases at least a few auditory neurons remain. The next question was whether the cochlear implant itself would destroy the remaining auditory neurons. Preliminary studies have shown that the nerve will survive the placement of electrodes both into the modiolus and the scala tympani. Several electrode materials and insulation have been found to be well tolerated, and there has been minimal damage from thermal or electrolytic processes; therefore, it appears feasible to stimulate the auditory nerve over a long period. Information Transfer by Electrical Stimulation. Single-channel stimulation produces only periodicity pitch, and information transfer is insufficient for speech discrimination. Experience to date indicates that it will be possible to produce both place and volley pitch by electrical stimulation with multiple electrodes in the scala tympani. These findings give promise for the feasibility of producing a device which will transfer sufficient information to produce speech discrimination. Present Status of the Cochlear Implant. To the present time 15 patients have been implanted with a unipolar electrode under the direction of the Ear Research Institute. These patients have all benefited from their devices. They are able to perceive background sounds and receive a cadence or rhythm to speech which makes the device helpful in lipreading. None of the patients have developed significant speech discrimination.", "contents": "The cochlear implant; basic principles. In recent years the cochlear implant has been a subject of much discussion and controversy. The clinician has often been confused by the conflicting reports of success and failure. In this paper the development of the cochlear implant is reviewed and its present status summarized. It is hoped that the clinician may thereby gain an understanding of this device so that he can better evaluate its present and future status. Selection of Patients for Cochlear Implantation. The cochlear implant will benefit only those patients with hair cell loss who have remaining viable auditory neurons. In order to determine whether viable neurons remain, an electric current is passed through a small needle which is place into the promontory through the tympanic membrane. If patients experience an auditory sensation as a result of this electrical stimulation, it is felt that they are suitable candidates for a cochlear implant. Feasibility of Long-Term VIIIth Nerve Stimulation. Many questions have been raised regarding the feasibility of long-term stimulation of the auditory nerve. The first question raised was whether the auditory nerve would survive severe hair cell degeneration. Studies have shown that in most cases at least a few auditory neurons remain. The next question was whether the cochlear implant itself would destroy the remaining auditory neurons. Preliminary studies have shown that the nerve will survive the placement of electrodes both into the modiolus and the scala tympani. Several electrode materials and insulation have been found to be well tolerated, and there has been minimal damage from thermal or electrolytic processes; therefore, it appears feasible to stimulate the auditory nerve over a long period. Information Transfer by Electrical Stimulation. Single-channel stimulation produces only periodicity pitch, and information transfer is insufficient for speech discrimination. Experience to date indicates that it will be possible to produce both place and volley pitch by electrical stimulation with multiple electrodes in the scala tympani. These findings give promise for the feasibility of producing a device which will transfer sufficient information to produce speech discrimination. Present Status of the Cochlear Implant. To the present time 15 patients have been implanted with a unipolar electrode under the direction of the Ear Research Institute. These patients have all benefited from their devices. They are able to perceive background sounds and receive a cadence or rhythm to speech which makes the device helpful in lipreading. None of the patients have developed significant speech discrimination."} {"id": "PMID:1256213", "title": "Sudden sensori-neural hearing impairment: a report of 1,220 cases.", "content": "We reviewed the findings in 1,220 cases of sudden sensori-neural hearing impairment encountered over a nine-year period at the Otologic Medical Group. A thorough neuro-otologic evaluation is indicated in each case. Ten patients had an acoustic tumor. A vasodilator regimen was prescribed in 380 cases and resulted in hearing improvement in 40%. Favorable prognostic findings were a low tone loss and absence of vertigo.", "contents": "Sudden sensori-neural hearing impairment: a report of 1,220 cases. We reviewed the findings in 1,220 cases of sudden sensori-neural hearing impairment encountered over a nine-year period at the Otologic Medical Group. A thorough neuro-otologic evaluation is indicated in each case. Ten patients had an acoustic tumor. A vasodilator regimen was prescribed in 380 cases and resulted in hearing improvement in 40%. Favorable prognostic findings were a low tone loss and absence of vertigo."} {"id": "PMID:1256214", "title": "Hearing impairment caused by intratympanic pressure changes during general anesthesia.", "content": "Hearing impairment is not often considered a potential complication of general anesthesia; however, four patients who sustained hearing loss following nitrous oxide inhalation anesthesia have recently come to the authors' attention. The cases are presented and middle ear pressure measurements taken during endotracheal inhalation anesthesia with various agents are reported. Factors predisposing to hearing loss during anesthesia are discussed.", "contents": "Hearing impairment caused by intratympanic pressure changes during general anesthesia. Hearing impairment is not often considered a potential complication of general anesthesia; however, four patients who sustained hearing loss following nitrous oxide inhalation anesthesia have recently come to the authors' attention. The cases are presented and middle ear pressure measurements taken during endotracheal inhalation anesthesia with various agents are reported. Factors predisposing to hearing loss during anesthesia are discussed."} {"id": "PMID:1256215", "title": "Carcinoma of the external auditory canal.", "content": "Successful management of carcinoma of the external auditory canal depends upon four factors: 1. early diagnosis is imperative if a high cure rate is to be expected; 2. correct evaluation of the extent of the malignancy; 3. adequate surgery based upon correct evaluation; and 4. postoperative radiation in certain selected cases. In this review of 35 cases, two factors were used to determine whether the disease was localized or extensive. When extension occurs inot the mastoid as deep as the middle ear cleft or into the facial nerve, it should be designated as extensive tumor. Tumors which do no go as deep as the facial nerve or involve the mucosa of the middle ear should be designated as localized tumors. In localized tumors, it is possible to perform a wide en bloc resection of the bony and cartilaginous external auditory canal including the tympanic membrane and malleus, and if necessary, including the superficial lobe of the parotid. Postoperative radiation is indicated when the pathological specimen shows unclear margins in the surgical dissection. With localized tumors, en bloc resection of the external auditory canal offers a high cure rate. In extensive lesions, an en bloc dissection removing the bulk of the tumor mass, followed by irradiation, seems to offer at least as good a prognosis as more radical surgery.", "contents": "Carcinoma of the external auditory canal. Successful management of carcinoma of the external auditory canal depends upon four factors: 1. early diagnosis is imperative if a high cure rate is to be expected; 2. correct evaluation of the extent of the malignancy; 3. adequate surgery based upon correct evaluation; and 4. postoperative radiation in certain selected cases. In this review of 35 cases, two factors were used to determine whether the disease was localized or extensive. When extension occurs inot the mastoid as deep as the middle ear cleft or into the facial nerve, it should be designated as extensive tumor. Tumors which do no go as deep as the facial nerve or involve the mucosa of the middle ear should be designated as localized tumors. In localized tumors, it is possible to perform a wide en bloc resection of the bony and cartilaginous external auditory canal including the tympanic membrane and malleus, and if necessary, including the superficial lobe of the parotid. Postoperative radiation is indicated when the pathological specimen shows unclear margins in the surgical dissection. With localized tumors, en bloc resection of the external auditory canal offers a high cure rate. In extensive lesions, an en bloc dissection removing the bulk of the tumor mass, followed by irradiation, seems to offer at least as good a prognosis as more radical surgery."} {"id": "PMID:1256216", "title": "Stapedectomy: gelfoam compared with tissue grafts.", "content": "The commonest causes of failure with the prefabricated wire loop-gel foam pad technique are inferior displacement of the loop in the window, high membrane formation and window fibrosis. As a result of these problems some members of the Otologic Medical Group have abandoned the use of gelfoam in favor of tissue grafts. A comparison of the results with gelfoam, fat grafts, and fascia grafts in 573 primary cases is made. Tissue grafts yielded a lower incidence of postoperative vertigo, of temporary and permanent sensori-neural hearing impairment, of fistulas and of long-term hearing regression. The conclusion is that a tissue graft is preferable to gelfoam as an oval window covering in stapedectomy.", "contents": "Stapedectomy: gelfoam compared with tissue grafts. The commonest causes of failure with the prefabricated wire loop-gel foam pad technique are inferior displacement of the loop in the window, high membrane formation and window fibrosis. As a result of these problems some members of the Otologic Medical Group have abandoned the use of gelfoam in favor of tissue grafts. A comparison of the results with gelfoam, fat grafts, and fascia grafts in 573 primary cases is made. Tissue grafts yielded a lower incidence of postoperative vertigo, of temporary and permanent sensori-neural hearing impairment, of fistulas and of long-term hearing regression. The conclusion is that a tissue graft is preferable to gelfoam as an oval window covering in stapedectomy."} {"id": "PMID:1256217", "title": "Technical note: A finger extension tongue depressor.", "content": "The author describes a tongue depressor which can be adapted to the examiner's thumb while performing indirect laryngoscopy. This depressor allows the examiner to pull the tongue and push it downward in patient where otherwise vision is obscured by the dorsum of the tongue.", "contents": "Technical note: A finger extension tongue depressor. The author describes a tongue depressor which can be adapted to the examiner's thumb while performing indirect laryngoscopy. This depressor allows the examiner to pull the tongue and push it downward in patient where otherwise vision is obscured by the dorsum of the tongue."} {"id": "PMID:1256263", "title": "[Conductometric method of studying aggregations of the formed elements of the blood].", "content": "To study an aggregation of formed blood cells a setup is proposed in which use is made of the conductometric method of measuring the resistance of a fine-pore filter through which the blood passes. A specially devised sensor allows it also to study the process of the cells aggregation in the vascular system of test animals and to control the dispersion of formed cells in the apparatus of extracoporeal circulation. Among advantages offered by the method are the objective character of measurement, the possibility of investigating the whole blood and due consideration of the part played by hydrodynamic factors.", "contents": "[Conductometric method of studying aggregations of the formed elements of the blood]. To study an aggregation of formed blood cells a setup is proposed in which use is made of the conductometric method of measuring the resistance of a fine-pore filter through which the blood passes. A specially devised sensor allows it also to study the process of the cells aggregation in the vascular system of test animals and to control the dispersion of formed cells in the apparatus of extracoporeal circulation. Among advantages offered by the method are the objective character of measurement, the possibility of investigating the whole blood and due consideration of the part played by hydrodynamic factors."} {"id": "PMID:1256265", "title": "[State of and prospects of the standardization of medical engineering terminology].", "content": "With a view to standardizing the biomedical engineering terminology some recommendations on elaborating scientific classification of terms covering the field of biomedical engineering and serving as a background to their formation are given.", "contents": "[State of and prospects of the standardization of medical engineering terminology]. With a view to standardizing the biomedical engineering terminology some recommendations on elaborating scientific classification of terms covering the field of biomedical engineering and serving as a background to their formation are given."} {"id": "PMID:1256267", "title": "[Principles of the unification of medical instruments].", "content": "Taking as a basis the calculation of the unification level index made according to the formula adopted in general machine building industry the need for determining the principle underlying the approach to unification of medical instruments is demonstrated. The paramount methodical prerequisite for unification of medical instruments is outlined and the unification of not only structural elements of the latter, but also of their mutual disposition is substantiated.", "contents": "[Principles of the unification of medical instruments]. Taking as a basis the calculation of the unification level index made according to the formula adopted in general machine building industry the need for determining the principle underlying the approach to unification of medical instruments is demonstrated. The paramount methodical prerequisite for unification of medical instruments is outlined and the unification of not only structural elements of the latter, but also of their mutual disposition is substantiated."} {"id": "PMID:1256264", "title": "[Hardening and polishing of polymeric articles for medical purposes].", "content": "Physico-mechanical and performance characteristics of manufactured articles made of polymers can be improved by treating their surfaces with active solvents during a certain period of time and at a fixed temperature. In such cases the solvent acts upon the molecular structure of the surfacial layer in the polymer, fills and cements its defects. Investigations carried out demonstrated that a short-term action of the solvent improves the durability and toughness of the articles, tends to raise their biological indifference and makes their external appearance look better.", "contents": "[Hardening and polishing of polymeric articles for medical purposes]. Physico-mechanical and performance characteristics of manufactured articles made of polymers can be improved by treating their surfaces with active solvents during a certain period of time and at a fixed temperature. In such cases the solvent acts upon the molecular structure of the surfacial layer in the polymer, fills and cements its defects. Investigations carried out demonstrated that a short-term action of the solvent improves the durability and toughness of the articles, tends to raise their biological indifference and makes their external appearance look better."} {"id": "PMID:1256268", "title": "[Some problems in the use of holography in medical-biological studies].", "content": "Various fields of the holographic methods application in medico-biological investigations are discussed. Special consideration is given to the methods of holographic interferometry, holographic microscopy, ultrasonic holography and to the technique of optic filtration of images. The paper sets forth brief characteristics of diverse holographic methods, technical possibilities of each one of them and a review of some practical work done in this field.", "contents": "[Some problems in the use of holography in medical-biological studies]. Various fields of the holographic methods application in medico-biological investigations are discussed. Special consideration is given to the methods of holographic interferometry, holographic microscopy, ultrasonic holography and to the technique of optic filtration of images. The paper sets forth brief characteristics of diverse holographic methods, technical possibilities of each one of them and a review of some practical work done in this field."} {"id": "PMID:1256272", "title": "[Improved stand for the IVCh-02 pallesthesiometer].", "content": "A support for the pallesthesiometer, model IVCh-02, which permits it to fix the position of the supper limb in measuring the vibration sensitivity threshold is proposed. This design ensures a stable digital pressure on the vibrator. The threshold levels of the vibration sensitivity registered by using this support are distinguished by lesser variability and greater accuracy as compared to those obtained with the batch-manufactured support.", "contents": "[Improved stand for the IVCh-02 pallesthesiometer]. A support for the pallesthesiometer, model IVCh-02, which permits it to fix the position of the supper limb in measuring the vibration sensitivity threshold is proposed. This design ensures a stable digital pressure on the vibrator. The threshold levels of the vibration sensitivity registered by using this support are distinguished by lesser variability and greater accuracy as compared to those obtained with the batch-manufactured support."} {"id": "PMID:1256269", "title": "[Serial spot roentgenokymography of the lungs].", "content": "A procedure employed in examining pulmonary functions with a Soviet-made roentgenokymograph and by using serial roentgenokymography is described. The procedure is relatively simple and can be effectively applied in any X-ray room. Four series of roentgenokymograms showing mid-segments of the both patient's lungs can be obtained on a single film with different respiration rates under physiological conditions and in making functional tests.", "contents": "[Serial spot roentgenokymography of the lungs]. A procedure employed in examining pulmonary functions with a Soviet-made roentgenokymograph and by using serial roentgenokymography is described. The procedure is relatively simple and can be effectively applied in any X-ray room. Four series of roentgenokymograms showing mid-segments of the both patient's lungs can be obtained on a single film with different respiration rates under physiological conditions and in making functional tests."} {"id": "PMID:1256276", "title": "[The model EN-57M apparatus for high-frequency electric surgery].", "content": "The model EN-57M apparatus is intended for cutting and coagulation of soft tissues with high-frequency currents and it represents a modernized version of the Model EN-57. In this new model the number of outlets has been increased, the set of accessories -- improved, the complement of monoactive electrodes -- broadened, a biactive pincer -- added and the design of passive electrodes -- changed. The active electrodes, electrode-holders and cables attached to them are manufactured of materials permitting their steam and air sterilization. Particular consideration has been given to the electric safety of the apparatus in providing protection against burns caused by the high-frequency current.", "contents": "[The model EN-57M apparatus for high-frequency electric surgery]. The model EN-57M apparatus is intended for cutting and coagulation of soft tissues with high-frequency currents and it represents a modernized version of the Model EN-57. In this new model the number of outlets has been increased, the set of accessories -- improved, the complement of monoactive electrodes -- broadened, a biactive pincer -- added and the design of passive electrodes -- changed. The active electrodes, electrode-holders and cables attached to them are manufactured of materials permitting their steam and air sterilization. Particular consideration has been given to the electric safety of the apparatus in providing protection against burns caused by the high-frequency current."} {"id": "PMID:1256270", "title": "[Technical means for the segmental perfusion of the small intestine].", "content": "One of the most exact methods of diagnosing disturbed absorption is perfusion of the small intestine. To make pertinent investigations a special perfusion probe manufactured of a roentgen-contrast rubber and a peristaltic pump for introducing a perfusion solution into the lumen of the intestine are proposed. A procedure used in conducting the examination is described and a formula for determining the absorption rate is given.", "contents": "[Technical means for the segmental perfusion of the small intestine]. One of the most exact methods of diagnosing disturbed absorption is perfusion of the small intestine. To make pertinent investigations a special perfusion probe manufactured of a roentgen-contrast rubber and a peristaltic pump for introducing a perfusion solution into the lumen of the intestine are proposed. A procedure used in conducting the examination is described and a formula for determining the absorption rate is given."} {"id": "PMID:1256273", "title": "[Informative nature of the \"momentary\" pulse in arrhythmia].", "content": "Changes in the \"momentary\" pulse characteristics serve as a possible background to establishing a tentative diagnosis of arrhythmias. The method is based on the evaluation of alternation of shortened and lengthened intervals between cardiac contractions and also on the appearance of isolated shortened or lengthened intervals between cardiac contractions.", "contents": "[Informative nature of the \"momentary\" pulse in arrhythmia]. Changes in the \"momentary\" pulse characteristics serve as a possible background to establishing a tentative diagnosis of arrhythmias. The method is based on the evaluation of alternation of shortened and lengthened intervals between cardiac contractions and also on the appearance of isolated shortened or lengthened intervals between cardiac contractions."} {"id": "PMID:1256282", "title": "[Methods of input into a digital computer of low-frequency physiological data].", "content": "A procedure employed for input of low-frequency physiological information coming via several channels in a digital computer, model M-220A has been worked out. The operations are effected through the application of standard equipment with the use of routine communication channels to the computer. Particular attention is attached to the storage of the input information in the permanent memory of the machine for further synchronous analysis of physiological indices. The procedure may find use in analyzing materials covering a wide range of medico-biological experiments.", "contents": "[Methods of input into a digital computer of low-frequency physiological data]. A procedure employed for input of low-frequency physiological information coming via several channels in a digital computer, model M-220A has been worked out. The operations are effected through the application of standard equipment with the use of routine communication channels to the computer. Particular attention is attached to the storage of the input information in the permanent memory of the machine for further synchronous analysis of physiological indices. The procedure may find use in analyzing materials covering a wide range of medico-biological experiments."} {"id": "PMID:1256311", "title": "Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes.", "content": "1. An attempt was made to evaluate the pathophysiology of symptoms of hyponatremia as related to changes in brain water and electrolytes. Studies were carried out in 66 hyponatremic patients and 5 groups of experimental animals. 2. In hyponatremic patients, symptoms (depression of sensorium, seizures) correlated well with plasma Na+ (r = 0.64, p less than .001), but there was substantial overlap. In patients with acute hyponatremia, all were symptomatic and 50% died. Among patients with hyponatremia of at least 3 days duration, sympatomatic patients had plasma Na+ (115 +/- 1 mEq/L) which was significantly less (p less than .001) than that of asymptomatic patients (plasma Na+ = 122 +/- 1 mEq/L). Among symptomatic patients, mortality was 12% and 8% had seizures, while none of the asymptomatic patients died or had seizures. 3. Among 14 patients with acute (less than 12 hrs) hyponatremia, the mean plasma Na+ was 112 +/- 2 mEq/L. All such patients had some depression of sensorium and four had grand male seizures. Seven of these patients were treated with hypertonic (862 mM) NaCl, while four were treated only with fluid restriction. Of the seven patients treated with hypertonic NaCl, five survived, while three of four patients treated with fluid restriction died. There was no evidence of circulatory congestion or cerebral damage in the patients treated with hypertonic NaCl. 4. Among rabbits with acute (2-3 hours) hyponatremia (plasma Na+ = 119 +/- 1 mEq/L), all had grand mal seizures and 86% died. All such animals had cerebral edema (brain H2O content 17% above control value) but brain content of Na+, K+ and Cl- was normal. 5. Rabbits with 3 1/2 days of hyponatremia (plasma Na+ = 122 +/- 2 mEq/L) appeared to be asymptomatic, even though brain water content was 7% above normal (p less than .01). 6. Rabbits with 16 days of more severe hyponatremia (plasma Na+ = 99 +/- 3 mEq/L) were weak, anorexic, lethargic and unable to walk. Brain water content was 7% above normal, although brain osmolality (218 +/- 12 mOsm/kg H2O) was similar to plasma (215 +/- 8 mOsm/kg). Brain content of Na+, K+, Cl- and osmoles was 17 to 37% less than normal values, so that the brain established osmotic equilibrium with plasma primarily by means of a loss of electrolytes. 7. These studies suggest that in patients with hyponatremia, symptoms and morbidity are only grossly correlated with either magnitude or duration of hyponatremia. Symptoms appear to correlate best with the interplay between a net increase in brain water versus a loss oof brain electrolytes. However, even asymptomatic animals have subclinical brain edema when plasma Na+ is below 125 mEq/L, and such edema may cause permanent brain damage. Thus, many patients with similar levels of plasma Na+, particularly when they are symptomatic, should probably be treated with hypertonic NaCl infusions.", "contents": "Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes. 1. An attempt was made to evaluate the pathophysiology of symptoms of hyponatremia as related to changes in brain water and electrolytes. Studies were carried out in 66 hyponatremic patients and 5 groups of experimental animals. 2. In hyponatremic patients, symptoms (depression of sensorium, seizures) correlated well with plasma Na+ (r = 0.64, p less than .001), but there was substantial overlap. In patients with acute hyponatremia, all were symptomatic and 50% died. Among patients with hyponatremia of at least 3 days duration, sympatomatic patients had plasma Na+ (115 +/- 1 mEq/L) which was significantly less (p less than .001) than that of asymptomatic patients (plasma Na+ = 122 +/- 1 mEq/L). Among symptomatic patients, mortality was 12% and 8% had seizures, while none of the asymptomatic patients died or had seizures. 3. Among 14 patients with acute (less than 12 hrs) hyponatremia, the mean plasma Na+ was 112 +/- 2 mEq/L. All such patients had some depression of sensorium and four had grand male seizures. Seven of these patients were treated with hypertonic (862 mM) NaCl, while four were treated only with fluid restriction. Of the seven patients treated with hypertonic NaCl, five survived, while three of four patients treated with fluid restriction died. There was no evidence of circulatory congestion or cerebral damage in the patients treated with hypertonic NaCl. 4. Among rabbits with acute (2-3 hours) hyponatremia (plasma Na+ = 119 +/- 1 mEq/L), all had grand mal seizures and 86% died. All such animals had cerebral edema (brain H2O content 17% above control value) but brain content of Na+, K+ and Cl- was normal. 5. Rabbits with 3 1/2 days of hyponatremia (plasma Na+ = 122 +/- 2 mEq/L) appeared to be asymptomatic, even though brain water content was 7% above normal (p less than .01). 6. Rabbits with 16 days of more severe hyponatremia (plasma Na+ = 99 +/- 3 mEq/L) were weak, anorexic, lethargic and unable to walk. Brain water content was 7% above normal, although brain osmolality (218 +/- 12 mOsm/kg H2O) was similar to plasma (215 +/- 8 mOsm/kg). Brain content of Na+, K+, Cl- and osmoles was 17 to 37% less than normal values, so that the brain established osmotic equilibrium with plasma primarily by means of a loss of electrolytes. 7. These studies suggest that in patients with hyponatremia, symptoms and morbidity are only grossly correlated with either magnitude or duration of hyponatremia. Symptoms appear to correlate best with the interplay between a net increase in brain water versus a loss oof brain electrolytes. However, even asymptomatic animals have subclinical brain edema when plasma Na+ is below 125 mEq/L, and such edema may cause permanent brain damage. Thus, many patients with similar levels of plasma Na+, particularly when they are symptomatic, should probably be treated with hypertonic NaCl infusions."} {"id": "PMID:1256322", "title": "[Fine-needle aspiration biopsy in the diagnosis of thyroid diseases (author's transl)].", "content": "879 fine-needle biopsies obtained from 754 patients with palpable lesions of the thyroid were evaluated. Cold nodules were identified in the scintigram of 509 patients. The cytologic findings could be checked by histology in 102 cases. 24 out of 26 malignant tumors of the thyroid were recognized cytologically. In 23 cases the tumor type was correctly identified by cytology. The cytologic report was false negative in two cases. Follicular adenoma and follicular carcinoma are not distinguishable on cytologic grounds. In 14.7% of patients the cytologic report stated cystic lesions and in 1.7% of patients inflammatory lesions.", "contents": "[Fine-needle aspiration biopsy in the diagnosis of thyroid diseases (author's transl)]. 879 fine-needle biopsies obtained from 754 patients with palpable lesions of the thyroid were evaluated. Cold nodules were identified in the scintigram of 509 patients. The cytologic findings could be checked by histology in 102 cases. 24 out of 26 malignant tumors of the thyroid were recognized cytologically. In 23 cases the tumor type was correctly identified by cytology. The cytologic report was false negative in two cases. Follicular adenoma and follicular carcinoma are not distinguishable on cytologic grounds. In 14.7% of patients the cytologic report stated cystic lesions and in 1.7% of patients inflammatory lesions."} {"id": "PMID:1256323", "title": "[Clinical significance of serum magnesium concentration in thyrotoxicosis (author's transl)].", "content": "Thyrotoxicosis is associated with hypomagnesemia. Therapy leads to restoration of serum magnesium concentration. The clinical significance of the disturbance in magnesium metabolism is discussed on results of two groups of patients with hyperthyroidism. One group of 7 patients with high serum thyroxine levels and mild clinical signs of thyrotoxicosis showed a normal magnesium concentration in serum. In a second group with further 7 patients serum magnesium level did not increase during therapy while thyroxine decreased in spite of lack of clinical improvement. The results suggest that serum magnesium concentration is primarily determined by 1-triiodothyronine.", "contents": "[Clinical significance of serum magnesium concentration in thyrotoxicosis (author's transl)]. Thyrotoxicosis is associated with hypomagnesemia. Therapy leads to restoration of serum magnesium concentration. The clinical significance of the disturbance in magnesium metabolism is discussed on results of two groups of patients with hyperthyroidism. One group of 7 patients with high serum thyroxine levels and mild clinical signs of thyrotoxicosis showed a normal magnesium concentration in serum. In a second group with further 7 patients serum magnesium level did not increase during therapy while thyroxine decreased in spite of lack of clinical improvement. The results suggest that serum magnesium concentration is primarily determined by 1-triiodothyronine."} {"id": "PMID:1256324", "title": "[Effect of experimentally induced hyperthyroidism on zona glomerulosa from adrenal cortex of the rat (author's transl)].", "content": "By histochemical and histometrical methods the the effect of l-triiodothyronine on the zona glomerulosa from rat adrenal cortex was investigated. Glucose-6-phosphatedehydrogenase and 3-beta-OH-steroiddehydrogenase activities were determined in slices of adrenal cortex. No increase in activities of these enzymes was observed after treatment with l-triiodothyronine. In contrast, histometrical studies showed a significant enlargement of nuclei in the zona glomerulosa as well as in the zona fasciculata. This observation suggests enhanced secretory activity of both zones of the adrenal cortex of the rat.", "contents": "[Effect of experimentally induced hyperthyroidism on zona glomerulosa from adrenal cortex of the rat (author's transl)]. By histochemical and histometrical methods the the effect of l-triiodothyronine on the zona glomerulosa from rat adrenal cortex was investigated. Glucose-6-phosphatedehydrogenase and 3-beta-OH-steroiddehydrogenase activities were determined in slices of adrenal cortex. No increase in activities of these enzymes was observed after treatment with l-triiodothyronine. In contrast, histometrical studies showed a significant enlargement of nuclei in the zona glomerulosa as well as in the zona fasciculata. This observation suggests enhanced secretory activity of both zones of the adrenal cortex of the rat."} {"id": "PMID:1256330", "title": "[Clinical experience with a new method for the determination of monoglyceride lipase (author's transl)].", "content": "The activity of monoglyceride lipase was studied in plasma from 74 patients with liver disease in whom blood was drawn 10 min after the injection of heparin (10 U/kg body weight). The results were compared with the activities from 29 healthy volunteers. For measurement a new, easy to handle method was used. The patients showed significantly lower activities, e.g. in chronic aggressive hepatitis there was a decrease by 87%. There was no correlation between the activities of monoglyceride lipase and pseudocholinesterase which also can be decreased in liver disease. The results show that the determination of monoglyceride lipase appears to be a useful test of the liver's function. Its value probably lies in the evaluation of the vessels.", "contents": "[Clinical experience with a new method for the determination of monoglyceride lipase (author's transl)]. The activity of monoglyceride lipase was studied in plasma from 74 patients with liver disease in whom blood was drawn 10 min after the injection of heparin (10 U/kg body weight). The results were compared with the activities from 29 healthy volunteers. For measurement a new, easy to handle method was used. The patients showed significantly lower activities, e.g. in chronic aggressive hepatitis there was a decrease by 87%. There was no correlation between the activities of monoglyceride lipase and pseudocholinesterase which also can be decreased in liver disease. The results show that the determination of monoglyceride lipase appears to be a useful test of the liver's function. Its value probably lies in the evaluation of the vessels."} {"id": "PMID:1256331", "title": "[Comparison between a titrimetric and a photometric method for determination of serum lipase activity (author's transl)].", "content": "Comparative studies of two methods for the determination of serum lipase activity (SLA) in human serum show in both methods, the one titrimetric the other photometric, a comparable sensivity and comparable results, especially within the group of subjects suffering from pancreactic diseases. The values of SLA within the group of 45 patients with acute and chronic pancreatic diseases and within a control group of 39 persons without pancreatic affections show a marked correlation for each group. The values of SLA obtained with the titrimetric method of Rick are found to be higher, which would be due to better conditions of the procedure. Also in the study of precision the titrimetric method gave a better result. The determination of SLA with both methods includes post-heparin-lipase-activity (PHLA).", "contents": "[Comparison between a titrimetric and a photometric method for determination of serum lipase activity (author's transl)]. Comparative studies of two methods for the determination of serum lipase activity (SLA) in human serum show in both methods, the one titrimetric the other photometric, a comparable sensivity and comparable results, especially within the group of subjects suffering from pancreactic diseases. The values of SLA within the group of 45 patients with acute and chronic pancreatic diseases and within a control group of 39 persons without pancreatic affections show a marked correlation for each group. The values of SLA obtained with the titrimetric method of Rick are found to be higher, which would be due to better conditions of the procedure. Also in the study of precision the titrimetric method gave a better result. The determination of SLA with both methods includes post-heparin-lipase-activity (PHLA)."} {"id": "PMID:1256332", "title": "[Distribution pattern of isoenzymes of alkaline phosphatase in patients with various forms of hepatitis (author's transl)].", "content": "The isoenzymes of alkaline phosphatase were measured on admission to hospital, and then weekly over a 2 to 3 month period, in 40 patients presenting with uncomplicated acute hepatitis, 12 patients with cholestatic hepatitis, and 10 patients with histologically confirmed chronic persistent hepatitis. In acute uncomplicated hepatitis the increase in total alkaline phosphatase is not due to a cholestatic reaction of the damaged liver, but reflects the impaired catabolic capacity of the liver cells to degrade alkaline phosphatases from intestine and bone, as well as that of hepato-biliary origin. The isoenzyme distribution pattern is the same as found in normal healthy subjects. The increase in total alkaline phosphatase in patients with cholestatic hepatitis results from this impaired catabolic capacity for degradation of all isoenzymes, together with an increase in cholestatic reflux of hepato-biliary enzymes. In patients with chronic persistent hepatitis the raised total alkaline phosphatase activity at each point during the illness is due to this catabolic impairment of degradation of all isoenzymes. A cholestasis is not seen. The isoenzyme distribution pattern remains normal; only the enzyme activity due to the intestinal fraction, when compared with the acute hepatitis, is slightly, but significantly, raised.", "contents": "[Distribution pattern of isoenzymes of alkaline phosphatase in patients with various forms of hepatitis (author's transl)]. The isoenzymes of alkaline phosphatase were measured on admission to hospital, and then weekly over a 2 to 3 month period, in 40 patients presenting with uncomplicated acute hepatitis, 12 patients with cholestatic hepatitis, and 10 patients with histologically confirmed chronic persistent hepatitis. In acute uncomplicated hepatitis the increase in total alkaline phosphatase is not due to a cholestatic reaction of the damaged liver, but reflects the impaired catabolic capacity of the liver cells to degrade alkaline phosphatases from intestine and bone, as well as that of hepato-biliary origin. The isoenzyme distribution pattern is the same as found in normal healthy subjects. The increase in total alkaline phosphatase in patients with cholestatic hepatitis results from this impaired catabolic capacity for degradation of all isoenzymes, together with an increase in cholestatic reflux of hepato-biliary enzymes. In patients with chronic persistent hepatitis the raised total alkaline phosphatase activity at each point during the illness is due to this catabolic impairment of degradation of all isoenzymes. A cholestasis is not seen. The isoenzyme distribution pattern remains normal; only the enzyme activity due to the intestinal fraction, when compared with the acute hepatitis, is slightly, but significantly, raised."} {"id": "PMID:1256334", "title": "[Hormon producing tumors of the pancreas. Verner-Morrison like symptomatology of a non-serotonin-producing, metastasizing carcinoid of the pancreas (author's transl)].", "content": "A case of Verner-Morrison like symptomatology of an histological identified, metastasizing, non-serotonin-producing carcinoid of the pancreas is described. The likeness of symptomatology to courses of disease by islet-cell tumors is pointed out, the coincidence of carcinoid and islet-cell-tumors and their common origin are discussed.", "contents": "[Hormon producing tumors of the pancreas. Verner-Morrison like symptomatology of a non-serotonin-producing, metastasizing carcinoid of the pancreas (author's transl)]. A case of Verner-Morrison like symptomatology of an histological identified, metastasizing, non-serotonin-producing carcinoid of the pancreas is described. The likeness of symptomatology to courses of disease by islet-cell tumors is pointed out, the coincidence of carcinoid and islet-cell-tumors and their common origin are discussed."} {"id": "PMID:1256336", "title": "[Salivary and duodenal amylase production in patients with chronic hepatic diseases (author's transl)].", "content": "Investigating patients with chronic diseases of the liver, there will sometimes be found a symmetric hypertrophy of the parotid glands. Supposing, that enlargement of the parotid glands could equal an enhancement of parotid function, the authors investigated amylase and volume production of the parotid glands and at the same time that produced by pancreatic excretion during pancreozymin/secretin stimulation. They found a compensatory action of the parotidean function: In patients with only small liver cell damage they saw a diminished parotidean function together with an enhanced pancreatic excretion. In cases with severe liver cell alteration, the parotidean function was found to be greater than in normals, the pancreatic function diminished. The authors estimate the parotidean hypertrophy as a morphologic equivalent to the compensatory enhancement of parotidean function in cases with chronic liver diseases.", "contents": "[Salivary and duodenal amylase production in patients with chronic hepatic diseases (author's transl)]. Investigating patients with chronic diseases of the liver, there will sometimes be found a symmetric hypertrophy of the parotid glands. Supposing, that enlargement of the parotid glands could equal an enhancement of parotid function, the authors investigated amylase and volume production of the parotid glands and at the same time that produced by pancreatic excretion during pancreozymin/secretin stimulation. They found a compensatory action of the parotidean function: In patients with only small liver cell damage they saw a diminished parotidean function together with an enhanced pancreatic excretion. In cases with severe liver cell alteration, the parotidean function was found to be greater than in normals, the pancreatic function diminished. The authors estimate the parotidean hypertrophy as a morphologic equivalent to the compensatory enhancement of parotidean function in cases with chronic liver diseases."} {"id": "PMID:1256337", "title": "[The serum prealbumin significance in differential diagnosis of the liver diseases (author's transl)].", "content": "We investigated the serum prealbumin by the immuno-diffusion method quantitatively according to the method of Manzini in 20 normal persons, 30 patients with hepatitis virosa acuta, 24 patients with hepatitis chronica and 11 patients with cirrhosis of the liver. The serum prealbumin was significantly decreased in patients with hepatitis acuta virosa, hepatitis chronica aggressiva and in cirrhosis of the liver, but in the patients with the hepatitis chronica persistens the serum prealbumin levels were normal or little increased. According to our results we concluded that the determination of serum prealbumin is important only for the differential diagnosis between the hepatitis chronica aggressiva and hepatitis chronica persistens. However these determinations are not of values in the differential diagnosis between hepatitis chronica aggressiva and cirrhosis of the liver.", "contents": "[The serum prealbumin significance in differential diagnosis of the liver diseases (author's transl)]. We investigated the serum prealbumin by the immuno-diffusion method quantitatively according to the method of Manzini in 20 normal persons, 30 patients with hepatitis virosa acuta, 24 patients with hepatitis chronica and 11 patients with cirrhosis of the liver. The serum prealbumin was significantly decreased in patients with hepatitis acuta virosa, hepatitis chronica aggressiva and in cirrhosis of the liver, but in the patients with the hepatitis chronica persistens the serum prealbumin levels were normal or little increased. According to our results we concluded that the determination of serum prealbumin is important only for the differential diagnosis between the hepatitis chronica aggressiva and hepatitis chronica persistens. However these determinations are not of values in the differential diagnosis between hepatitis chronica aggressiva and cirrhosis of the liver."} {"id": "PMID:1256375", "title": "Test cassette for measuring peak tube potential of diagnostic x-ray machines.", "content": "A test cassette employing a modification of the Ardran-Crooks attenuation technique for measuring peak tube potential (and half-value layer) is described. The technique employs a radiographic intensifying screen which is exposed to a hardened x-ray beam. Copper penetrameters are used to determine the attenuator thickness which reduces the light output from the screen to that transmitted by an optical attenuator over an adjacent area of the screen. The test cassette was calibrated by using x-ray machines whose high voltages were measured electrically. The test cassette has a measurement precision of +/- 1 kVp and an accuracy of +/- 3 kVp or better in the range 50-130 kVp for x-ray generators with the same voltage waveform.", "contents": "Test cassette for measuring peak tube potential of diagnostic x-ray machines. A test cassette employing a modification of the Ardran-Crooks attenuation technique for measuring peak tube potential (and half-value layer) is described. The technique employs a radiographic intensifying screen which is exposed to a hardened x-ray beam. Copper penetrameters are used to determine the attenuator thickness which reduces the light output from the screen to that transmitted by an optical attenuator over an adjacent area of the screen. The test cassette was calibrated by using x-ray machines whose high voltages were measured electrically. The test cassette has a measurement precision of +/- 1 kVp and an accuracy of +/- 3 kVp or better in the range 50-130 kVp for x-ray generators with the same voltage waveform."} {"id": "PMID:1256376", "title": "Computer dosimetry for flattened and wedged fast-neutron beams.", "content": "Beam flattening by the use of polyethylene filters has been developed for the 50-MeV d in equilibrium Be fast-neutron therapy beam at the Texas A&M Variable-Energy Cyclotron (TAMVEC) as a result of the need for a more uniform dose distribution at depth within the patient. A computer algorithm has been developed that allows the use of a modified decrement line method to calculate dose distributions; standards decrement line methods do not apply because of off-axis peaking. The dose distributions for measured flattened beams are transformed into distributions that are physically equivalent to an unflattened distribution. In the transformed space, standard decrement line theory yields a distribution for any field size which, by applying the inverse transformation, generates the flattened dose distribution, including the off-axis peaking. A semiempirical model has been constructed that allows the calculation of dose distributions for wedged beams from open-beam data.", "contents": "Computer dosimetry for flattened and wedged fast-neutron beams. Beam flattening by the use of polyethylene filters has been developed for the 50-MeV d in equilibrium Be fast-neutron therapy beam at the Texas A&M Variable-Energy Cyclotron (TAMVEC) as a result of the need for a more uniform dose distribution at depth within the patient. A computer algorithm has been developed that allows the use of a modified decrement line method to calculate dose distributions; standards decrement line methods do not apply because of off-axis peaking. The dose distributions for measured flattened beams are transformed into distributions that are physically equivalent to an unflattened distribution. In the transformed space, standard decrement line theory yields a distribution for any field size which, by applying the inverse transformation, generates the flattened dose distribution, including the off-axis peaking. A semiempirical model has been constructed that allows the calculation of dose distributions for wedged beams from open-beam data."} {"id": "PMID:1256377", "title": "High-resolution dosimetry with stimulated phosphorescence.", "content": "Thermally stimulated radiophosphorescence has been studied as a means of high-resolution dosimetry. Small grains of CaSO4:Mn phosphor, embedded in a thin Teflon tape, constitute the dosimeter. The light emitted after irradiation is measured with a photomultiplier coupled to the eyepiece of a scanning microscope. With CaSO4:Mn, the phosphorescence at room temperature is sufficient for measurement after doses in excess of 3000 rads. The spatial resolution of the technique is about 0.2 mm. The method has been tested by measuring the dose distributions from a radium needle and a beta-emitting eye applicator.", "contents": "High-resolution dosimetry with stimulated phosphorescence. Thermally stimulated radiophosphorescence has been studied as a means of high-resolution dosimetry. Small grains of CaSO4:Mn phosphor, embedded in a thin Teflon tape, constitute the dosimeter. The light emitted after irradiation is measured with a photomultiplier coupled to the eyepiece of a scanning microscope. With CaSO4:Mn, the phosphorescence at room temperature is sufficient for measurement after doses in excess of 3000 rads. The spatial resolution of the technique is about 0.2 mm. The method has been tested by measuring the dose distributions from a radium needle and a beta-emitting eye applicator."} {"id": "PMID:1256448", "title": "Hydrophobic surface properties of erythrocytes studied by affinity partition in aqueous two-phase systems.", "content": "Erythrocytes from various species have been partitioned in aqueous two-phase systems consisting of water, dextran, poly-(ethylene glycol), salt and buffer. The terminal hydroxyl groups of the latter polymer were esterified with palmitic, oleic, linoleic and linolenic acids, as well as with deoxycholic acid. In a two-phase system containing unesterified poly(ethylene glycol) the erythrocytes are exclusively in the dextran-rich lower phase. When the poly(ethylene glycol)-rich upper phase depending on the type and concentration of esterified acid. Palmitate ester is most effective in increasing the affinity of the cells for the upper phase, followed by oleate, linolate, linolenate, and deoxycholate esters. The partition behaviour of erythrocytes from various species differs considerably. Two groups can be distinguished: one consisting of erythrocytes from dog, guinea pig and rat, the other from human, sheep and rabbit. This division can be correlated to the content of sphingomyelin and phosphatidyl choline in the erythrocyte membranes.", "contents": "Hydrophobic surface properties of erythrocytes studied by affinity partition in aqueous two-phase systems. Erythrocytes from various species have been partitioned in aqueous two-phase systems consisting of water, dextran, poly-(ethylene glycol), salt and buffer. The terminal hydroxyl groups of the latter polymer were esterified with palmitic, oleic, linoleic and linolenic acids, as well as with deoxycholic acid. In a two-phase system containing unesterified poly(ethylene glycol) the erythrocytes are exclusively in the dextran-rich lower phase. When the poly(ethylene glycol)-rich upper phase depending on the type and concentration of esterified acid. Palmitate ester is most effective in increasing the affinity of the cells for the upper phase, followed by oleate, linolate, linolenate, and deoxycholate esters. The partition behaviour of erythrocytes from various species differs considerably. Two groups can be distinguished: one consisting of erythrocytes from dog, guinea pig and rat, the other from human, sheep and rabbit. This division can be correlated to the content of sphingomyelin and phosphatidyl choline in the erythrocyte membranes."} {"id": "PMID:1256450", "title": "[Methods of approach used by physicials untrained in behaviour therapy to reduce anxiety in children undergoing routine examination (author's transl)].", "content": "Samples of pediatricians (N = 50), general practitioners (N = 50) and doctors of a children's hospital (N = 30) were asked to rate the intensity of children's anxiety for 15 items of routine medical performances. In addition the first two groups were asked about the technique used to reduce children's anxiety or to hold it on a low level. The questionnaires were analysed under the following aspects: 1) Are there systematic differences between the three groups concerning the estimation of infantile fear-intensity?--2) Is it possible to express the described behaviour doctors regard as effective for anxiety-reduction in terms of learning theory or behaviour-therapy respectively?--3) Is there a statistical interaction between the estimation of fear-intensity and ways of approaching?--Concerning the estimation of children's fear-intensity the three groups turned out to be highly concordant. Nearly 60% of pediatricians and general practitioners at least once during a session use approaching-techniques in the sense of learning theory. There is no interaction between the two variables \"fear-intensity-estimation\" and \"mode of approach\".", "contents": "[Methods of approach used by physicials untrained in behaviour therapy to reduce anxiety in children undergoing routine examination (author's transl)]. Samples of pediatricians (N = 50), general practitioners (N = 50) and doctors of a children's hospital (N = 30) were asked to rate the intensity of children's anxiety for 15 items of routine medical performances. In addition the first two groups were asked about the technique used to reduce children's anxiety or to hold it on a low level. The questionnaires were analysed under the following aspects: 1) Are there systematic differences between the three groups concerning the estimation of infantile fear-intensity?--2) Is it possible to express the described behaviour doctors regard as effective for anxiety-reduction in terms of learning theory or behaviour-therapy respectively?--3) Is there a statistical interaction between the estimation of fear-intensity and ways of approaching?--Concerning the estimation of children's fear-intensity the three groups turned out to be highly concordant. Nearly 60% of pediatricians and general practitioners at least once during a session use approaching-techniques in the sense of learning theory. There is no interaction between the two variables \"fear-intensity-estimation\" and \"mode of approach\"."} {"id": "PMID:1256451", "title": "[The application of a combined Xylose-lactose tolerance-test in children with suspected malabsorption (author's transl)].", "content": "A combined xylose-lactose tolerance-test and a duodenal biopsy were performed in 68 children with suspected malabsorption-syndrome. The purpose of the present work was to assess the diagnostic value of xylose concentrations in blood at different times and to determine the additional discriminatory value to glucose levels. The contribution of the glucose rise to a calculated discriminant function is statistically significant but practically negligible and therefore does not justify its determination. A small-bowel biopsy is recommended if the concentration of xylose after 60 min is less than 26 mg/100 ml or the increment of xylose concentration above fasting level is 18 mg/100 ml or less.", "contents": "[The application of a combined Xylose-lactose tolerance-test in children with suspected malabsorption (author's transl)]. A combined xylose-lactose tolerance-test and a duodenal biopsy were performed in 68 children with suspected malabsorption-syndrome. The purpose of the present work was to assess the diagnostic value of xylose concentrations in blood at different times and to determine the additional discriminatory value to glucose levels. The contribution of the glucose rise to a calculated discriminant function is statistically significant but practically negligible and therefore does not justify its determination. A small-bowel biopsy is recommended if the concentration of xylose after 60 min is less than 26 mg/100 ml or the increment of xylose concentration above fasting level is 18 mg/100 ml or less."} {"id": "PMID:1256452", "title": "[Intermittent branched--chain ketoacidurie in ketotic hypoglycemia: investigations to localize the biochemical defect (author's transl)].", "content": "We are reporting a girl aged eight years with ketotic hypoglycemia, mental deficiency and retarded motor and somatic development. Investigation of plasma amino acid concentrations during a spontaneous hypoglycemia revealed an increase in the branched-chain amino acids valine (4.1), leucine (7.8) and isoleucine (1.7 mg/100 ml), while alanine was decreased (1.2 mg/100 ml) and ketonuria was present. The determination of the branched-chain ketoacid decarboxylase in leukocytes showed a decrease of approximately 50% of normal for alpha-ketoisocaproic acid (KIC) as substrate, whereas values for alpha-ketoisovaleric acid (KIVA) and alpha-keto-beta-methylvaleric acid (MEVA) were normal. In fibroblasts activities for all three substrates were in the normal range. Intermittend maple-syrup-urine disease was excluded by oral loading tests with the branched-chain amino acids and with an isocaloric, high-protein diet. Impairment of oxydative decarboxylation of leucine, valine, and isoleucine secondary to increased ketogenesis may play an etiologic role in ketotic hypoglycemia, since we observed, by gaschromatographic analysis, an increase in the urinary excretion of KIVA (5.5 mumol/h), KIC (29.4), and MEVA (47.9) after a provocative test with an isocaloric ketogenic diet for 36 hrs. The significance of branched-chain hyperaminoacidemia and branched chain alpha-ketoaciduria is discussed in this context.", "contents": "[Intermittent branched--chain ketoacidurie in ketotic hypoglycemia: investigations to localize the biochemical defect (author's transl)]. We are reporting a girl aged eight years with ketotic hypoglycemia, mental deficiency and retarded motor and somatic development. Investigation of plasma amino acid concentrations during a spontaneous hypoglycemia revealed an increase in the branched-chain amino acids valine (4.1), leucine (7.8) and isoleucine (1.7 mg/100 ml), while alanine was decreased (1.2 mg/100 ml) and ketonuria was present. The determination of the branched-chain ketoacid decarboxylase in leukocytes showed a decrease of approximately 50% of normal for alpha-ketoisocaproic acid (KIC) as substrate, whereas values for alpha-ketoisovaleric acid (KIVA) and alpha-keto-beta-methylvaleric acid (MEVA) were normal. In fibroblasts activities for all three substrates were in the normal range. Intermittend maple-syrup-urine disease was excluded by oral loading tests with the branched-chain amino acids and with an isocaloric, high-protein diet. Impairment of oxydative decarboxylation of leucine, valine, and isoleucine secondary to increased ketogenesis may play an etiologic role in ketotic hypoglycemia, since we observed, by gaschromatographic analysis, an increase in the urinary excretion of KIVA (5.5 mumol/h), KIC (29.4), and MEVA (47.9) after a provocative test with an isocaloric ketogenic diet for 36 hrs. The significance of branched-chain hyperaminoacidemia and branched chain alpha-ketoaciduria is discussed in this context."} {"id": "PMID:1256453", "title": "[Cerebral salt loss as Schwartz-Bartter-syndrome in childhood (author's transl)].", "content": "Schwartz-Bartter-syndrome as a consequence of severe cerebral alterations like bacterial and tuberculous meningitis, encephalitis, hydrocephalus and brain haemorrhage has been observed in 7 cases. Massive natriuresis is followed by marked hyponatremia and hypochloremia which may lead to an intracellular brain edema. Sodium administered even in high dosage is lost rapidly through the kidney, and does not normalize the serum level of sodium. The Schwartz-Bartter-syndrome is caused by inadequatly elevated ADH-secretion with consecutive water retention and an increase in plasma volume. Consecutively an increased excretion of sodium takes place causing a substantial loss of bound water. An analogous situation was seen in a child with neurohormonal diabetes insipidus after an overdosage of ADH, which resulted in a hypervolemia, marked hyponatremia and massive natriuresis. The increased excretion of sodium may be the result of reduced reabsorption of sodium in the proximal tubuli of the kidney, caused by a humeral natriuretic factor (the socalled \"third factor\"). In the serum of one of our patients an increased natriuretic activity could be shown; this is the first time in a child with Schwartz-Bartter-syndrome.", "contents": "[Cerebral salt loss as Schwartz-Bartter-syndrome in childhood (author's transl)]. Schwartz-Bartter-syndrome as a consequence of severe cerebral alterations like bacterial and tuberculous meningitis, encephalitis, hydrocephalus and brain haemorrhage has been observed in 7 cases. Massive natriuresis is followed by marked hyponatremia and hypochloremia which may lead to an intracellular brain edema. Sodium administered even in high dosage is lost rapidly through the kidney, and does not normalize the serum level of sodium. The Schwartz-Bartter-syndrome is caused by inadequatly elevated ADH-secretion with consecutive water retention and an increase in plasma volume. Consecutively an increased excretion of sodium takes place causing a substantial loss of bound water. An analogous situation was seen in a child with neurohormonal diabetes insipidus after an overdosage of ADH, which resulted in a hypervolemia, marked hyponatremia and massive natriuresis. The increased excretion of sodium may be the result of reduced reabsorption of sodium in the proximal tubuli of the kidney, caused by a humeral natriuretic factor (the socalled \"third factor\"). In the serum of one of our patients an increased natriuretic activity could be shown; this is the first time in a child with Schwartz-Bartter-syndrome."} {"id": "PMID:1256454", "title": "[The therapeutic significance of bronchial suction-drainage in infants].", "content": "Bronchial suction-drainage in infants--according to our observations--is a life-saving procedure in cases of aspiration, severe bronchitis and retention of bronchial secretion. It can also be very effective in atelectasis, bronchopneumonia and pulmonary abscess. The earlier the drainage the quicker the clearing up of the atelectasis. An additional indication for performing bronchial suction in severe lower respiratory tract infections is to gagain secretion for bacterial culture. This is especially important in the Gram negative and Staphylococcus infections of young infants. The right upper pulmonary lobe is the most common localisation for atelectasis and pneumonia in this age group. One possible explanation for this could be that malformed bronchi are more frequently found in the right than in the left upper lobe. It is such a characteristical phenomenon in infancy that we called it \"the right upper lobe syndrome\".", "contents": "[The therapeutic significance of bronchial suction-drainage in infants]. Bronchial suction-drainage in infants--according to our observations--is a life-saving procedure in cases of aspiration, severe bronchitis and retention of bronchial secretion. It can also be very effective in atelectasis, bronchopneumonia and pulmonary abscess. The earlier the drainage the quicker the clearing up of the atelectasis. An additional indication for performing bronchial suction in severe lower respiratory tract infections is to gagain secretion for bacterial culture. This is especially important in the Gram negative and Staphylococcus infections of young infants. The right upper pulmonary lobe is the most common localisation for atelectasis and pneumonia in this age group. One possible explanation for this could be that malformed bronchi are more frequently found in the right than in the left upper lobe. It is such a characteristical phenomenon in infancy that we called it \"the right upper lobe syndrome\"."} {"id": "PMID:1256455", "title": "[Summer holiday camp for children with chronic renal disease (author's transl)].", "content": "A summer camp was organized for 31 children with chronic renal disease. One third of the patients suffered from renal insufficiency. The medical and paedagogical problems which evolved during the stay could be solved satisfactorily under relatively simple external conditions. The camp offered opportunity for the detection of hidden psychosocial and behavioral problems induced by the disease. These could be treated appropriately. The most important prerequisite for the organization of summer camps of this kind is a well-trained and coordinated team which should include a paediatric nephrologist, psychologists, teachers, dieticians and social workers.", "contents": "[Summer holiday camp for children with chronic renal disease (author's transl)]. A summer camp was organized for 31 children with chronic renal disease. One third of the patients suffered from renal insufficiency. The medical and paedagogical problems which evolved during the stay could be solved satisfactorily under relatively simple external conditions. The camp offered opportunity for the detection of hidden psychosocial and behavioral problems induced by the disease. These could be treated appropriately. The most important prerequisite for the organization of summer camps of this kind is a well-trained and coordinated team which should include a paediatric nephrologist, psychologists, teachers, dieticians and social workers."} {"id": "PMID:1256456", "title": "[Hemodialysis in a child with accidental digitalis poisoning (author's transl)].", "content": "A case of an accidental digitalis intoxication in a two year old child is reported. Early Hemodialysis effectively reduced the high plasma levels of digoxin and replaced other therapeutical procedures.", "contents": "[Hemodialysis in a child with accidental digitalis poisoning (author's transl)]. A case of an accidental digitalis intoxication in a two year old child is reported. Early Hemodialysis effectively reduced the high plasma levels of digoxin and replaced other therapeutical procedures."} {"id": "PMID:1256457", "title": "[Rapidly progressive glomerulonephritis in a child. Clinical and histological observation over 3 1/2 years (author's transl)].", "content": "At the age of 5 years and 10 months a boy suffered from rapidly progressive glomerulonephritis. After 14 days of treatment with peritoneal dialysis and chlorambucil the acute renal failure was overcome and the kidneys started to function again. 3 1/2 years later 2/3 of normal values for glomerular filtration had been regained, though proteinuria is still 2,8 g/day. Histologically mainly extracapillary proliferations and a partially necrotizing glomerulonephritis were seen in the beginning. 1 1/4 years later sklerosed glomerula predominated (80%) over almost normal glomerula with only minor proliferations. The prognosis remains doubtful in spite of the benign course in the beginning.", "contents": "[Rapidly progressive glomerulonephritis in a child. Clinical and histological observation over 3 1/2 years (author's transl)]. At the age of 5 years and 10 months a boy suffered from rapidly progressive glomerulonephritis. After 14 days of treatment with peritoneal dialysis and chlorambucil the acute renal failure was overcome and the kidneys started to function again. 3 1/2 years later 2/3 of normal values for glomerular filtration had been regained, though proteinuria is still 2,8 g/day. Histologically mainly extracapillary proliferations and a partially necrotizing glomerulonephritis were seen in the beginning. 1 1/4 years later sklerosed glomerula predominated (80%) over almost normal glomerula with only minor proliferations. The prognosis remains doubtful in spite of the benign course in the beginning."} {"id": "PMID:1256458", "title": "[The campomelic syndrome (author's transl)].", "content": "Case report of a male infant who died from asphyxia on the second day of life and who exhibited typical features of the campomelic syndrome: odd facies, bowing of the long bones of the legs, skeletal deformities, cleft palate. There was also coarctatio of the aorta and probably aplasia of the fibula.", "contents": "[The campomelic syndrome (author's transl)]. Case report of a male infant who died from asphyxia on the second day of life and who exhibited typical features of the campomelic syndrome: odd facies, bowing of the long bones of the legs, skeletal deformities, cleft palate. There was also coarctatio of the aorta and probably aplasia of the fibula."} {"id": "PMID:1256459", "title": "[DeBarsy-Moens-Dierckx-syndrome (author's transl)].", "content": "The symptoms of DeBarsy-Moens-Dierckx-syndrome previously described only in single patients, have been observed in a brother and a sister. Both children showed dwarfism, dystrophy, oligophrenia, an old looking face, and a typically lax skin and cloudy cornea as signs of degeneration of the elastic tissue. Moderate pathological changes were also found in the electroencephalogram, the echoencephalogram, and the X-ray films of the wrists. The analysis of the chromosomes and many other laboratory data were normal. The family-history gave no clue as far as the heredity mode is concerned. As far as we know this is the first description of this syndrome in siblings.", "contents": "[DeBarsy-Moens-Dierckx-syndrome (author's transl)]. The symptoms of DeBarsy-Moens-Dierckx-syndrome previously described only in single patients, have been observed in a brother and a sister. Both children showed dwarfism, dystrophy, oligophrenia, an old looking face, and a typically lax skin and cloudy cornea as signs of degeneration of the elastic tissue. Moderate pathological changes were also found in the electroencephalogram, the echoencephalogram, and the X-ray films of the wrists. The analysis of the chromosomes and many other laboratory data were normal. The family-history gave no clue as far as the heredity mode is concerned. As far as we know this is the first description of this syndrome in siblings."} {"id": "PMID:1256460", "title": "[Ultrastructure of the interstitial cells of the rat kidney medulla].", "content": "Ultrastructure of the interstitial cells of the internal zone of the medulla of kidney in rats is detailly described. Electronmicroscopical feature of these cells may be connected with several functions i.e. urine-concentration, electrolyte-transport, production of intercellular matrix and vasodepressor-lipids. Ultrastructural picture of production and elimination of lipid droplets is not yet cleared out. Authors stress, that for the appropriate fixation of zones of different ion-concentration of the medulla special fixatives of an appropriate osmotic pressure are necessary.", "contents": "[Ultrastructure of the interstitial cells of the rat kidney medulla]. Ultrastructure of the interstitial cells of the internal zone of the medulla of kidney in rats is detailly described. Electronmicroscopical feature of these cells may be connected with several functions i.e. urine-concentration, electrolyte-transport, production of intercellular matrix and vasodepressor-lipids. Ultrastructural picture of production and elimination of lipid droplets is not yet cleared out. Authors stress, that for the appropriate fixation of zones of different ion-concentration of the medulla special fixatives of an appropriate osmotic pressure are necessary."} {"id": "PMID:1256462", "title": "[Electron microscopic observations in leukoedema exfoliativum mucosae oris (white sponge nevus)].", "content": "Biopsia taken from 13 cases of leukoderma exfoliativum mucosae oris (white sponge nevus) was investigated by the aid of electron microscope. Significant changes as compaired to the normal ultrastructure were revealed. The disease is a hereditary one manifesting itself in the disturbance of differentiation of epithelial cells mainly of the oral mucosa. Arrangment of the tonofilaments is disturbed, formation of tonofibrills and keratohyaline granules ceases. Odland-bodies occure in a great number but the lack of emptiing their content into the interecellular space is striking. Exfoliation of the epithelial cells diminishes, presumably because of the disturbance of their enzymatic function and the presence of a great number of desmosomes between the cells of the superficial layer. The diminished exfoliation histologically and clinically produces a hyerplasia of the epithelium with an enormous quantitity of superficial epithelial cells.", "contents": "[Electron microscopic observations in leukoedema exfoliativum mucosae oris (white sponge nevus)]. Biopsia taken from 13 cases of leukoderma exfoliativum mucosae oris (white sponge nevus) was investigated by the aid of electron microscope. Significant changes as compaired to the normal ultrastructure were revealed. The disease is a hereditary one manifesting itself in the disturbance of differentiation of epithelial cells mainly of the oral mucosa. Arrangment of the tonofilaments is disturbed, formation of tonofibrills and keratohyaline granules ceases. Odland-bodies occure in a great number but the lack of emptiing their content into the interecellular space is striking. Exfoliation of the epithelial cells diminishes, presumably because of the disturbance of their enzymatic function and the presence of a great number of desmosomes between the cells of the superficial layer. The diminished exfoliation histologically and clinically produces a hyerplasia of the epithelium with an enormous quantitity of superficial epithelial cells."} {"id": "PMID:1256463", "title": "[The effect of atherogenic diet on the entering of albumin into surviving segments of rabbit aortic wall].", "content": "Damage to the endothelial cells in the early phase of atherosclerosis is of essential importance. Presence of an anhomogen layer of endothelial cells revealed in vivo, represents an early lesion of the area of vessel well influenced heavily by haemodinamics. Authors have established that entering of albumin into the aortic wall of rabbits exposed to a cholesterin-rich diet in the early phase of atherosclerosis-in vitro-increases, but later on in the advanced phase of the disease decreases, which can be explained by the slow-down of the speed of diffusion into the vessel wall. Accumulation of plasma-constituents in the vessel wall in the early phases of the vascular lesion is caused by the increase of entering of the plasma, in the advanced stages by the slow-down of the speed of diffusion.", "contents": "[The effect of atherogenic diet on the entering of albumin into surviving segments of rabbit aortic wall]. Damage to the endothelial cells in the early phase of atherosclerosis is of essential importance. Presence of an anhomogen layer of endothelial cells revealed in vivo, represents an early lesion of the area of vessel well influenced heavily by haemodinamics. Authors have established that entering of albumin into the aortic wall of rabbits exposed to a cholesterin-rich diet in the early phase of atherosclerosis-in vitro-increases, but later on in the advanced phase of the disease decreases, which can be explained by the slow-down of the speed of diffusion into the vessel wall. Accumulation of plasma-constituents in the vessel wall in the early phases of the vascular lesion is caused by the increase of entering of the plasma, in the advanced stages by the slow-down of the speed of diffusion."} {"id": "PMID:1256464", "title": "[Changes in the structure of the wall of the human thoracic duct in relation to atherosclerosis and age].", "content": "Changes in the proportion of muscular- and connective tissue in the media of the thoracic duct were observed at atherosclerotic persons. It was established that the quotient of the muscular and connective tissue with the development of the atherosclerotic process increases. The latter causes thichkening of the connective tissue layer in the wall of the thoracic duct. These structural changes have only indirect connection with age, since severe atherosclerosis in aged persons occure more often.", "contents": "[Changes in the structure of the wall of the human thoracic duct in relation to atherosclerosis and age]. Changes in the proportion of muscular- and connective tissue in the media of the thoracic duct were observed at atherosclerotic persons. It was established that the quotient of the muscular and connective tissue with the development of the atherosclerotic process increases. The latter causes thichkening of the connective tissue layer in the wall of the thoracic duct. These structural changes have only indirect connection with age, since severe atherosclerosis in aged persons occure more often."} {"id": "PMID:1256465", "title": "[Unusual case of fire-arm injury].", "content": "A rare case of firearm-injury is described. The bullet getting into the sigmoid colon by the antiperistaltics was transferred into the colon transversum.", "contents": "[Unusual case of fire-arm injury]. A rare case of firearm-injury is described. The bullet getting into the sigmoid colon by the antiperistaltics was transferred into the colon transversum."} {"id": "PMID:1256466", "title": "[Gas chromatography of alcoholic beverages].", "content": "The author carried out investigations on mixed fruit and grape brady obtainable in shops, as well as on the alcohol of the mixtures of 500 wine samples by means of gaschromatography, partly without preliminary preparation, and partly after extraction with ether and pentane respectively. It was established that the extraction method with ether and pentane accepted in the literature is suitable for the concentration of the side products of alcoholic beverages and thus for their gaschromatographic qualitative analisis as well. When examing higher alcohols - and also other side-products - the direct, examination without preliminary preparation must be given preference, because in this case there is also a possibility for quantitative determination. On the basis of his results the author considers an increased quality control of home distilled brandy necessary as well as the determination of alcohols of higher order, because in some cases he has detected a greater quality of fusel oil content than permissable (400 mg/100 ml albolute alcohol).", "contents": "[Gas chromatography of alcoholic beverages]. The author carried out investigations on mixed fruit and grape brady obtainable in shops, as well as on the alcohol of the mixtures of 500 wine samples by means of gaschromatography, partly without preliminary preparation, and partly after extraction with ether and pentane respectively. It was established that the extraction method with ether and pentane accepted in the literature is suitable for the concentration of the side products of alcoholic beverages and thus for their gaschromatographic qualitative analisis as well. When examing higher alcohols - and also other side-products - the direct, examination without preliminary preparation must be given preference, because in this case there is also a possibility for quantitative determination. On the basis of his results the author considers an increased quality control of home distilled brandy necessary as well as the determination of alcohols of higher order, because in some cases he has detected a greater quality of fusel oil content than permissable (400 mg/100 ml albolute alcohol)."} {"id": "PMID:1256467", "title": "[Forensic problems of fatal hand-inflicted injuries].", "content": "In the last years in Hungary continual decrease of homicidal cases could be registered, however other forms of violence, severe injuries followed by the death of the victim are almost as high as formerly. Author in the last ten years performed autopsy of 14 such cases. On the base of them summarizes problems arising in connection with the medico-legal investigation of them. He concludes that among these problems-beside alcoholic intoxication-the most important is to reveal the natural disease-if any-of the victim. If there is a natural disease it may be accounted as a factor in the death. Then the crime can be evaluated as a praeterintentional one.", "contents": "[Forensic problems of fatal hand-inflicted injuries]. In the last years in Hungary continual decrease of homicidal cases could be registered, however other forms of violence, severe injuries followed by the death of the victim are almost as high as formerly. Author in the last ten years performed autopsy of 14 such cases. On the base of them summarizes problems arising in connection with the medico-legal investigation of them. He concludes that among these problems-beside alcoholic intoxication-the most important is to reveal the natural disease-if any-of the victim. If there is a natural disease it may be accounted as a factor in the death. Then the crime can be evaluated as a praeterintentional one."} {"id": "PMID:1256468", "title": "[Electron microscopic study of kidney biopsy specimens from children].", "content": "Investigation of kidney-biopsy taken from 17 children was carried out. The techniques used were: light-microscopic investigation of paraffin sections and ultrathin sections, electron microscopic investigation of the latter and basal-membrane measurements. According to the author's opinion electron microscopic investigation of kidney-biopsy is reasonable only in selected cases, representing special clinical and therapeutic problems. In cases of nephrosis syndrome electron microscopy helps in differentiation of the \"mimimal lesion\" and the early phase of the focal sclerotizing glomerular lesion. Further it gives good results in observation of mono- and olygosystemic diseases of the kidney. In the author's material electron microscopy contributed to more differentiated morphological diagnosis in 2/3 rds of the cases investigated. The authors join to the opinion of other investigators stressing that light-microscopical investigation should be completed by the light-microscopy of uktrathin scretions even then, when there are no possibilities of electonmicroscopical study.", "contents": "[Electron microscopic study of kidney biopsy specimens from children]. Investigation of kidney-biopsy taken from 17 children was carried out. The techniques used were: light-microscopic investigation of paraffin sections and ultrathin sections, electron microscopic investigation of the latter and basal-membrane measurements. According to the author's opinion electron microscopic investigation of kidney-biopsy is reasonable only in selected cases, representing special clinical and therapeutic problems. In cases of nephrosis syndrome electron microscopy helps in differentiation of the \"mimimal lesion\" and the early phase of the focal sclerotizing glomerular lesion. Further it gives good results in observation of mono- and olygosystemic diseases of the kidney. In the author's material electron microscopy contributed to more differentiated morphological diagnosis in 2/3 rds of the cases investigated. The authors join to the opinion of other investigators stressing that light-microscopical investigation should be completed by the light-microscopy of uktrathin scretions even then, when there are no possibilities of electonmicroscopical study."} {"id": "PMID:1256470", "title": "Sucrase-isomaltase deficiency. Absence of an inactive enzyme variant.", "content": "Deficiency of sucrase-isomaltase, an intestinal enzyme complex that is essential for digestion of nutritionally important carbohydrates, appears to be inherited as an autosomal recessive in 0.2 per cent of North Americans. The molecular basis of the deficiency has not been elucidated. To characterize the enzyme defect quantitatively, papain-solubilized intestinal biopsies were analyzed for total enzyme protein by radioimmunoassay and for enzyme activity by hydrolytic assay. Normal intestine had a close correlation between immunologically reactive enzyme and enzymic activity. In contrast, seven patients with sucrase-isomaltase deficiency were found to have complete absence of the enzyme protein by radioimmunoassay even though up to 10 times more intestinal protein was present than with normal tissue. This absence of an inactive enzyme variant can be explained by a major (no-sense) mutation of the structural gene or by a complete repression of the regulatory mechanism that controls structural gene function.", "contents": "Sucrase-isomaltase deficiency. Absence of an inactive enzyme variant. Deficiency of sucrase-isomaltase, an intestinal enzyme complex that is essential for digestion of nutritionally important carbohydrates, appears to be inherited as an autosomal recessive in 0.2 per cent of North Americans. The molecular basis of the deficiency has not been elucidated. To characterize the enzyme defect quantitatively, papain-solubilized intestinal biopsies were analyzed for total enzyme protein by radioimmunoassay and for enzyme activity by hydrolytic assay. Normal intestine had a close correlation between immunologically reactive enzyme and enzymic activity. In contrast, seven patients with sucrase-isomaltase deficiency were found to have complete absence of the enzyme protein by radioimmunoassay even though up to 10 times more intestinal protein was present than with normal tissue. This absence of an inactive enzyme variant can be explained by a major (no-sense) mutation of the structural gene or by a complete repression of the regulatory mechanism that controls structural gene function."} {"id": "PMID:1256482", "title": "Salicylate-induced injury of pyruvate-kinase-deficient erythrocytes.", "content": "Salicylate is known to uncouple mitochondrial oxidative phosphorylation. Since the viability of pyruvate-kinase-deficient reticulocytes depends on ATP generated by mitochondrial metabolism, this study examined the effects of salicylate on erythrocytes deficient in pyruvate kinase. When deficient erythrocytes from patients with severe hemolysis were incubated with salicylate (2 to 30 mg per deciliter), there was a marked decrease (25 to 75 percent) in ATP. In addition, this drug-induced ATP depletion produced cell potassium and water loss, and the normal oxidant responsiveness of the hexose-monophosphate shunt was blunted. Since these cellular abnormalities are associated with accelerated hemolysis in vivo, the data suggest that aspirin therapy may aggravate hemolysis in patients with pyruvate kinase deficiency whose erythrocyte manifest sensitivity to salicylate in vitro.", "contents": "Salicylate-induced injury of pyruvate-kinase-deficient erythrocytes. Salicylate is known to uncouple mitochondrial oxidative phosphorylation. Since the viability of pyruvate-kinase-deficient reticulocytes depends on ATP generated by mitochondrial metabolism, this study examined the effects of salicylate on erythrocytes deficient in pyruvate kinase. When deficient erythrocytes from patients with severe hemolysis were incubated with salicylate (2 to 30 mg per deciliter), there was a marked decrease (25 to 75 percent) in ATP. In addition, this drug-induced ATP depletion produced cell potassium and water loss, and the normal oxidant responsiveness of the hexose-monophosphate shunt was blunted. Since these cellular abnormalities are associated with accelerated hemolysis in vivo, the data suggest that aspirin therapy may aggravate hemolysis in patients with pyruvate kinase deficiency whose erythrocyte manifest sensitivity to salicylate in vitro."} {"id": "PMID:1256483", "title": "A controlled trial of multiphasic screening.", "content": "A clinical controlled trial was designed to determine the impact of Automated Multiphasic Health Testing on morbidity and attitudes. Three strata comprising 574 families (lower-income group enrolled in health maintenance organization, lower-income not enrolled in such a project, and a middle-income group employed by a utility company) were interviewed to obtain information on utilization, morbidity, health status, and attitudes. Sixty percent of adults in each stratum were then screened. All families were interviewed again one year later. The only significant difference found between screened and non-screened subjects was an increase in nights hospitalized for screened subjects. Physicians were interviewed to determine what abnormalities were found and what treatment was required for project and privately referred patients of these physicians. Previously unknown abnormalities prompted retesting for confirmation in only 28 per cent of the cases and even less often led to treatment.", "contents": "A controlled trial of multiphasic screening. A clinical controlled trial was designed to determine the impact of Automated Multiphasic Health Testing on morbidity and attitudes. Three strata comprising 574 families (lower-income group enrolled in health maintenance organization, lower-income not enrolled in such a project, and a middle-income group employed by a utility company) were interviewed to obtain information on utilization, morbidity, health status, and attitudes. Sixty percent of adults in each stratum were then screened. All families were interviewed again one year later. The only significant difference found between screened and non-screened subjects was an increase in nights hospitalized for screened subjects. Physicians were interviewed to determine what abnormalities were found and what treatment was required for project and privately referred patients of these physicians. Previously unknown abnormalities prompted retesting for confirmation in only 28 per cent of the cases and even less often led to treatment."} {"id": "PMID:1256508", "title": "Grief response of parents after referral of the critically ill newborn to a regional center.", "content": "Attitudes, feelings, and behavior were studied in 101 mother-father pairs whose critically ill newborn infants survived after referral from the hospital of birth to a regional neonatal intensive-care unit for special care. As measured by an anticipatory-grief score, most parents experienced grief reactions similar to those whose infants do not survive the newborn period. The level of anticipatory grief did not appear to be associated with severity of infant illness as determined by the need for respirator therapy or major surgical procedures. The fathers reported drastic alteration in daily activity while wife and infant were hospitalized in separate facilities, and they assumed a central role in maintaining family stability during the crisis. These data suggest that an organized family-support program could play a prominent part in maintaining family stability during the delivery of newborn intensive care.", "contents": "Grief response of parents after referral of the critically ill newborn to a regional center. Attitudes, feelings, and behavior were studied in 101 mother-father pairs whose critically ill newborn infants survived after referral from the hospital of birth to a regional neonatal intensive-care unit for special care. As measured by an anticipatory-grief score, most parents experienced grief reactions similar to those whose infants do not survive the newborn period. The level of anticipatory grief did not appear to be associated with severity of infant illness as determined by the need for respirator therapy or major surgical procedures. The fathers reported drastic alteration in daily activity while wife and infant were hospitalized in separate facilities, and they assumed a central role in maintaining family stability during the crisis. These data suggest that an organized family-support program could play a prominent part in maintaining family stability during the delivery of newborn intensive care."} {"id": "PMID:1256510", "title": "Thyroid cancer occurring as a late consequence of head-and-neck irradiation. Evaluation of 1056 patients.", "content": "From January 1 to September 30, 1974, we examined 1056 of 5266 subjects (20.1%) who had received therapeutic irradiation primarily for infections and inflammatory disease of the upper respiratory tract at our institution during the 1940's and 1950's. The tonsillar and nasopharyngeal region was the treatment site in 85% of those examined. Palpable nodular thyroid disease was found in 16.5%, and nonpalpable lesions were detected by 99m Tc pertechnetate thyroid imaging in an additional 10.7%, for a prevalence of nodular disease of 27.2%. Operation on 71% with nodular disease revealed thyroid cancer in 33% (60 of 182). Preliminary analysis for potential risk factors suggests a correlation between radiation exposure and the presence of thyroid nodules (P less than 0.001). These findings indicate that nodular thyroid disease, both benign and malignant, continues as a major health problem for at least 35 years in exposed subjects.", "contents": "Thyroid cancer occurring as a late consequence of head-and-neck irradiation. Evaluation of 1056 patients. From January 1 to September 30, 1974, we examined 1056 of 5266 subjects (20.1%) who had received therapeutic irradiation primarily for infections and inflammatory disease of the upper respiratory tract at our institution during the 1940's and 1950's. The tonsillar and nasopharyngeal region was the treatment site in 85% of those examined. Palpable nodular thyroid disease was found in 16.5%, and nonpalpable lesions were detected by 99m Tc pertechnetate thyroid imaging in an additional 10.7%, for a prevalence of nodular disease of 27.2%. Operation on 71% with nodular disease revealed thyroid cancer in 33% (60 of 182). Preliminary analysis for potential risk factors suggests a correlation between radiation exposure and the presence of thyroid nodules (P less than 0.001). These findings indicate that nodular thyroid disease, both benign and malignant, continues as a major health problem for at least 35 years in exposed subjects."} {"id": "PMID:1256511", "title": "Protein patterns of brush-border fragments in congenital lactose malabsorption and in specific hypolactasia of the adult.", "content": "Brush-border membrane proteins of the small-bowel mucosa were separated on polyacrylamide gels from intestinal biopsy specimens obtained from four children with congenital lactose malabsorption and from two adults with specific hypolactasia. In three patients with the congenital type of lactase deficiency the protein band corresponding to brush-border lactase was reduced in intensity, but was never completely absent. No difference in gel patterns was detected when this pattern in congenital deficiency was compared to that obtained from the two patients with adult-type selective hypolactasia. In one patient with congenital lactose malabsorption the protein band corresponding to lactase activity was not detectable. The findings suggest that the mechanisms leading to low lactase activity in the congenital and adult forms of lactose intolerance are similar.", "contents": "Protein patterns of brush-border fragments in congenital lactose malabsorption and in specific hypolactasia of the adult. Brush-border membrane proteins of the small-bowel mucosa were separated on polyacrylamide gels from intestinal biopsy specimens obtained from four children with congenital lactose malabsorption and from two adults with specific hypolactasia. In three patients with the congenital type of lactase deficiency the protein band corresponding to brush-border lactase was reduced in intensity, but was never completely absent. No difference in gel patterns was detected when this pattern in congenital deficiency was compared to that obtained from the two patients with adult-type selective hypolactasia. In one patient with congenital lactose malabsorption the protein band corresponding to lactase activity was not detectable. The findings suggest that the mechanisms leading to low lactase activity in the congenital and adult forms of lactose intolerance are similar."} {"id": "PMID:1256523", "title": "Lung function and risk of myocardial infarction and sudden cardiac death.", "content": "In a serach for risk factors for myocardial infarction and sudden cardiac death, the mean total vital capacity as measured at multiphasic health checkups was lower in persons who later had a first myocardial infarction than in risk-factor-matched controls (3.17 vs. 3.29 liters, 395 pairs, P less than 0.05) and non-risk-factor-matched controls (3.16 vs. 3.41 liters, 401 pairs, P less than 0.001). Findings were little affected by age and height adjustment and were similar for sudden cardiac death. The first-second vital capacity was also inversely related to later development of these conditions, but the ratio of that measurement to total vital capacity was not. Heavy smoking, productive cough, exertional dyspnea and cardiac enlargement were associated with diminished total capacity. However, exclusion of subjects with these findings did not reduce the predictive value of total vital capacity. Diminished vital capacity deserves continued attention as a possible coronary risk factor. Its relation to subsequent coronary events is not well explained.", "contents": "Lung function and risk of myocardial infarction and sudden cardiac death. In a serach for risk factors for myocardial infarction and sudden cardiac death, the mean total vital capacity as measured at multiphasic health checkups was lower in persons who later had a first myocardial infarction than in risk-factor-matched controls (3.17 vs. 3.29 liters, 395 pairs, P less than 0.05) and non-risk-factor-matched controls (3.16 vs. 3.41 liters, 401 pairs, P less than 0.001). Findings were little affected by age and height adjustment and were similar for sudden cardiac death. The first-second vital capacity was also inversely related to later development of these conditions, but the ratio of that measurement to total vital capacity was not. Heavy smoking, productive cough, exertional dyspnea and cardiac enlargement were associated with diminished total capacity. However, exclusion of subjects with these findings did not reduce the predictive value of total vital capacity. Diminished vital capacity deserves continued attention as a possible coronary risk factor. Its relation to subsequent coronary events is not well explained."} {"id": "PMID:1256524", "title": "Effect of ketosis on respiratory sensitivity to carbon dioxide in obesity.", "content": "We investigated whether the respiratory defect in the obesity-hypoventilation syndrome might respond to dietary manipulation. The effects of hypocaloric ketogenic regimens on the ventilatory response to carbon dioxide were studied in a manner excluding changes in weight or thoracic mechanics as factors. Six obese subjects with hyporesponse (less than 1.1 1/min/mm Hg) and 12 with normal response were fasted or given a diet containing 400 kcal per day of protein. During ketosis carbon dioxide response more than doubled in those with hyporesponse (0.8 +/- 0.1 to 1.8 +/- 1/min/mm Hg, P less than 0.05) but was unchanged in those with normal response. This improvement could not be accounted for by changes in weight, pulmonary function, pH or degree of ketosis between the two groups. However, a significant positive (r = 0.70; P less than 0.001) correlation between ketone-body concentrations and carbon dioxide response was observed in subjects with hyporesponse. These results indicate that depressed sensitivity to carbon dioxide in obese patients can be increased by dietary manipulation.", "contents": "Effect of ketosis on respiratory sensitivity to carbon dioxide in obesity. We investigated whether the respiratory defect in the obesity-hypoventilation syndrome might respond to dietary manipulation. The effects of hypocaloric ketogenic regimens on the ventilatory response to carbon dioxide were studied in a manner excluding changes in weight or thoracic mechanics as factors. Six obese subjects with hyporesponse (less than 1.1 1/min/mm Hg) and 12 with normal response were fasted or given a diet containing 400 kcal per day of protein. During ketosis carbon dioxide response more than doubled in those with hyporesponse (0.8 +/- 0.1 to 1.8 +/- 1/min/mm Hg, P less than 0.05) but was unchanged in those with normal response. This improvement could not be accounted for by changes in weight, pulmonary function, pH or degree of ketosis between the two groups. However, a significant positive (r = 0.70; P less than 0.001) correlation between ketone-body concentrations and carbon dioxide response was observed in subjects with hyporesponse. These results indicate that depressed sensitivity to carbon dioxide in obese patients can be increased by dietary manipulation."} {"id": "PMID:1256525", "title": "Prevalence of clinical mitral-valve prolapse in 1169 young women.", "content": "Eleven hundred and sixty-nine young women were prospectively examined for the presence of mitral-valve prolapse as manifested by midsystolic non-ejection click or late systolic murmur (or both). Of the 1169 women 74 (6.3%) had physical findings consistent with mitral-valve prolapse. Sixty-eight of the 74 (92%) had midsystolic non-ejection click, and in 57 the click was accompanied by a late systolic murmur. In six (8%) only a late systolic murmur was heard. Echocardiography on all patients with clinical diagnosis of mitral-valve prolapse showed patterns of prolapse in 60 of 74 (81%). Fourteen (19%) had negative echocardiograms. We conclude that mitral-valve prolapse is clinically present in approximately 6.3% of otherwise healthy young women.", "contents": "Prevalence of clinical mitral-valve prolapse in 1169 young women. Eleven hundred and sixty-nine young women were prospectively examined for the presence of mitral-valve prolapse as manifested by midsystolic non-ejection click or late systolic murmur (or both). Of the 1169 women 74 (6.3%) had physical findings consistent with mitral-valve prolapse. Sixty-eight of the 74 (92%) had midsystolic non-ejection click, and in 57 the click was accompanied by a late systolic murmur. In six (8%) only a late systolic murmur was heard. Echocardiography on all patients with clinical diagnosis of mitral-valve prolapse showed patterns of prolapse in 60 of 74 (81%). Fourteen (19%) had negative echocardiograms. We conclude that mitral-valve prolapse is clinically present in approximately 6.3% of otherwise healthy young women."} {"id": "PMID:1256542", "title": "T4 gene 32 protein model for control of activity at replication fork.", "content": "Limited hydrolysis of gene 32 protein by various proteinases results in the production of three stable cleavage products. Two of these products show an affinity for native T4 DNA cellulose that the uncleaved protein does not exhibit. A model for proteolytic cleavage and for the total unwinding of DNA in advance of the replication fork is discussed in terms of this unusual binding affinity.", "contents": "T4 gene 32 protein model for control of activity at replication fork. Limited hydrolysis of gene 32 protein by various proteinases results in the production of three stable cleavage products. Two of these products show an affinity for native T4 DNA cellulose that the uncleaved protein does not exhibit. A model for proteolytic cleavage and for the total unwinding of DNA in advance of the replication fork is discussed in terms of this unusual binding affinity."} {"id": "PMID:1256543", "title": "Body weight, diet and home range area in primates.", "content": "Primates show a strong positive relationship between body weight and home range area. Dietary habits also influence home range area. Folivorous primates occupy smaller home range areas for their body weight than do frugivores and omnivores. Primates generally require smaller home range area per individual than solitary terrestrial mammals, but primates living in social groups have much larger total home range than individual solitary mammals. This trend may necessitate higher expenditures of energy in food-gathering or modifications in movement patterns.", "contents": "Body weight, diet and home range area in primates. Primates show a strong positive relationship between body weight and home range area. Dietary habits also influence home range area. Folivorous primates occupy smaller home range areas for their body weight than do frugivores and omnivores. Primates generally require smaller home range area per individual than solitary terrestrial mammals, but primates living in social groups have much larger total home range than individual solitary mammals. This trend may necessitate higher expenditures of energy in food-gathering or modifications in movement patterns."} {"id": "PMID:1256552", "title": "Stable nuclear activation dependent on a protein synthesised during oogenesis.", "content": "A protein synthesised during oogenesis seems to be essential for the activation, during blastulation, of the nuclear genes essential for gastrulation and organogenesis. Nuclear transplantation experiments show that this interaction between the protein and the blastula nucleus produces a heritable state of nuclear activation.", "contents": "Stable nuclear activation dependent on a protein synthesised during oogenesis. A protein synthesised during oogenesis seems to be essential for the activation, during blastulation, of the nuclear genes essential for gastrulation and organogenesis. Nuclear transplantation experiments show that this interaction between the protein and the blastula nucleus produces a heritable state of nuclear activation."} {"id": "PMID:1256553", "title": "Developmental shifts in the synthesis of heterogeneous nuclear RNA classes in the sea urchin embryo.", "content": "Three molecular classes with different properties can be distinguished in the heterogeneous nuclear RNA (HnRNA) of sea urchin embryos. The relative proportions of these classes, which we have previously designated alpha, beta and gamma HnRNA, undergo marked changes during development from morula to early gastrula. Such changes suggest the existence of more than a single HnRNA function, as well as specific roles for different HnRNA classes in embryonic development.", "contents": "Developmental shifts in the synthesis of heterogeneous nuclear RNA classes in the sea urchin embryo. Three molecular classes with different properties can be distinguished in the heterogeneous nuclear RNA (HnRNA) of sea urchin embryos. The relative proportions of these classes, which we have previously designated alpha, beta and gamma HnRNA, undergo marked changes during development from morula to early gastrula. Such changes suggest the existence of more than a single HnRNA function, as well as specific roles for different HnRNA classes in embryonic development."} {"id": "PMID:1256560", "title": "alpha-Chain contacts in the polymerisation of sickle haemogloblin.", "content": "Five new double-mutant haemoglobins composed of betaS chains and alpha chains with different substitutions, which are located at the surface of the tetramer, have been prepared. Although all the hybrids are more soluble than deoxyhaemoglobin S, the individual differences between these molecules make it possible to evaluate several regions on the alpha chains for intermolecular contacts in the polymerisation of deoxyhaemoglobin S.", "contents": "alpha-Chain contacts in the polymerisation of sickle haemogloblin. Five new double-mutant haemoglobins composed of betaS chains and alpha chains with different substitutions, which are located at the surface of the tetramer, have been prepared. Although all the hybrids are more soluble than deoxyhaemoglobin S, the individual differences between these molecules make it possible to evaluate several regions on the alpha chains for intermolecular contacts in the polymerisation of deoxyhaemoglobin S."} {"id": "PMID:1256568", "title": "Sequence of promoter for coat protein gene of bacteriophage fd.", "content": "The nucleotide sequence in the promoter region for the coat protein gene of phage fd has been determined. This sequence contains an endonuclease R-Hha cleavage site at the fifteenth nucleotide upstream from the RNA start site. Cleavage results in loss of promoter function. Comparison with the sequence of another fd promoter indicates that the longest sequence common to both was TATAAT in the region in which RNA polymerase forms a stable initiation complex.", "contents": "Sequence of promoter for coat protein gene of bacteriophage fd. The nucleotide sequence in the promoter region for the coat protein gene of phage fd has been determined. This sequence contains an endonuclease R-Hha cleavage site at the fifteenth nucleotide upstream from the RNA start site. Cleavage results in loss of promoter function. Comparison with the sequence of another fd promoter indicates that the longest sequence common to both was TATAAT in the region in which RNA polymerase forms a stable initiation complex."} {"id": "PMID:1256625", "title": "[Chronic leukemia coexisting with hypophyseal tumor].", "content": "The author describes a case of hypophyseal tumor coexisting with chronic leukaemia. It is suggested that both these processes coexisted from the very beginning of the disease. Development of hypothalmo-hypophyseal system failure was due to the presence of hypophyseal tumour while intensification of these manifestations in the last stage of the disease was caused by the presence of leukaemic changes in the central nervous system.", "contents": "[Chronic leukemia coexisting with hypophyseal tumor]. The author describes a case of hypophyseal tumor coexisting with chronic leukaemia. It is suggested that both these processes coexisted from the very beginning of the disease. Development of hypothalmo-hypophyseal system failure was due to the presence of hypophyseal tumour while intensification of these manifestations in the last stage of the disease was caused by the presence of leukaemic changes in the central nervous system."} {"id": "PMID:1256627", "title": "[Diagnostic difficulties in brain strokes in the light of personal observations].", "content": "The authors report a clinico-neuropathological analysis of 350 case records and autopsy protocols of patients dying from stroke in the years 1962-1966 at the Department of Neurology of the Groch\u00f3w Hospital in Warsaw. Full agreement of clinical diagnosis and autopsy diagnosis was found in 314 cases while in 36 cases (about 10%) the clinical diagnosis was not correct. The authors believe that the diagnostic difficulties encountered by clinicians are due frequently to a complex pathological mechanism of vasogenic lesions in the brain and frequency of encephalomalatic foci found in the same patient beside haemorrhagic lesions. In the present material 116 (33%) such cases have been found.", "contents": "[Diagnostic difficulties in brain strokes in the light of personal observations]. The authors report a clinico-neuropathological analysis of 350 case records and autopsy protocols of patients dying from stroke in the years 1962-1966 at the Department of Neurology of the Groch\u00f3w Hospital in Warsaw. Full agreement of clinical diagnosis and autopsy diagnosis was found in 314 cases while in 36 cases (about 10%) the clinical diagnosis was not correct. The authors believe that the diagnostic difficulties encountered by clinicians are due frequently to a complex pathological mechanism of vasogenic lesions in the brain and frequency of encephalomalatic foci found in the same patient beside haemorrhagic lesions. In the present material 116 (33%) such cases have been found."} {"id": "PMID:1256628", "title": "[Venous blood concentration of pyruvates in patients with stroke].", "content": "The concentration of pyruvate in the venous blood of 31 patients with stroke was determined by the enzymatic spectrophotometric method. The pyruvate concentration was raised on the 1st, 3rd and 10th days after stroke and this increase was statistically significant. Pyruvate concentration changes in venous blood were associated with severe clinical condition of the patients.", "contents": "[Venous blood concentration of pyruvates in patients with stroke]. The concentration of pyruvate in the venous blood of 31 patients with stroke was determined by the enzymatic spectrophotometric method. The pyruvate concentration was raised on the 1st, 3rd and 10th days after stroke and this increase was statistically significant. Pyruvate concentration changes in venous blood were associated with severe clinical condition of the patients."} {"id": "PMID:1256629", "title": "[Cathemnesis of patients with myasthenia].", "content": "Fifty patients with myasthenia were followed up, including 26 surgically treated cases (thymectomy) and 24 conservatively treated ones. Improvement was obtained after thymectomy in 10 cases (73%) and in 12 (50%) conservatively treated cases. Sixteen patients died, including 6 (23%) treated surgically and 10 (41.6%) treated conservatively. Good results of surgical and conservative treatment were observed in cases with mild or moderately severe course. In severe cases of myasthenia (with respiratory disturbances) surgical and conservative treatment was ineffective. Thymectomy should be carried out early before appearance of respratory failure.", "contents": "[Cathemnesis of patients with myasthenia]. Fifty patients with myasthenia were followed up, including 26 surgically treated cases (thymectomy) and 24 conservatively treated ones. Improvement was obtained after thymectomy in 10 cases (73%) and in 12 (50%) conservatively treated cases. Sixteen patients died, including 6 (23%) treated surgically and 10 (41.6%) treated conservatively. Good results of surgical and conservative treatment were observed in cases with mild or moderately severe course. In severe cases of myasthenia (with respiratory disturbances) surgical and conservative treatment was ineffective. Thymectomy should be carried out early before appearance of respratory failure."} {"id": "PMID:1256630", "title": "[EEG pattern during treatment of parkinsonism with L-dopa].", "content": "The authors studied the dynamics of EEG changes in 27 patients treated with L-dopa. The records obtained before treatment were compared with those made during treatment and with the clinical manifestations. In 8 cases the EEG pattern was normal before treatment and 6 of them improved (three-fourths of this subgroup). In 19 cases the EEG pattern was abnormal and 10 of them improved (about 50%). Some intensification of temporal episodic complexes in EEG records was observed during treatment without concomitant changes of clinical manifestations. In 2 cases with slowed down background activity in initial records psychic disturbances of hallucinatory obnubilation type developed requiring withdrawal of treatment. This psychotic reaction was characterized in EEG with increased intensity of generalized slowing down of EEG activity.", "contents": "[EEG pattern during treatment of parkinsonism with L-dopa]. The authors studied the dynamics of EEG changes in 27 patients treated with L-dopa. The records obtained before treatment were compared with those made during treatment and with the clinical manifestations. In 8 cases the EEG pattern was normal before treatment and 6 of them improved (three-fourths of this subgroup). In 19 cases the EEG pattern was abnormal and 10 of them improved (about 50%). Some intensification of temporal episodic complexes in EEG records was observed during treatment without concomitant changes of clinical manifestations. In 2 cases with slowed down background activity in initial records psychic disturbances of hallucinatory obnubilation type developed requiring withdrawal of treatment. This psychotic reaction was characterized in EEG with increased intensity of generalized slowing down of EEG activity."} {"id": "PMID:1256631", "title": "[Direct magnification technic as a method of further improving the diagnostic value of cerebral angiography].", "content": "The authors report an evaluation of own results obtained using a technique of direct magnification which is a trial of further improvement of the diagnostic possibilities of cerebral arteriography. In the light of personal experiences and available literature the authors express the view that introduction of this method, especially in connection with traction, will increase significantly the possibility of diagnosis of various pathological processes.", "contents": "[Direct magnification technic as a method of further improving the diagnostic value of cerebral angiography]. The authors report an evaluation of own results obtained using a technique of direct magnification which is a trial of further improvement of the diagnostic possibilities of cerebral arteriography. In the light of personal experiences and available literature the authors express the view that introduction of this method, especially in connection with traction, will increase significantly the possibility of diagnosis of various pathological processes."} {"id": "PMID:1256632", "title": "[Post-traumatic petroso-nasal cerebrospinal fluid fistula].", "content": "The authors present five cases of posttraumatic petronosal fistulas. The stress the rarity of these cases, their anatomo-pathological aspects, the pathophysiological consequences of the osteo-meningeal fissure and the necessity of the neurosurgical treatment.", "contents": "[Post-traumatic petroso-nasal cerebrospinal fluid fistula]. The authors present five cases of posttraumatic petronosal fistulas. The stress the rarity of these cases, their anatomo-pathological aspects, the pathophysiological consequences of the osteo-meningeal fissure and the necessity of the neurosurgical treatment."} {"id": "PMID:1256634", "title": "[Retinal changes in subacute sclerosing panencephalitis].", "content": "In a 12-year-old boy with histologically confirmed subacute sclerosing panencephalitis changes resembling chorioretinitis were found in the peripheral part of the left retina. Fluorescein angiography demonstrated signs of atrophy of pigmented epithelium. On the basis of pertinent literature the authors suggest that in this disease retinal involvement may precede neurological manifestations. It would be interesting to try whether therapy applied in this early stage would be effective.", "contents": "[Retinal changes in subacute sclerosing panencephalitis]. In a 12-year-old boy with histologically confirmed subacute sclerosing panencephalitis changes resembling chorioretinitis were found in the peripheral part of the left retina. Fluorescein angiography demonstrated signs of atrophy of pigmented epithelium. On the basis of pertinent literature the authors suggest that in this disease retinal involvement may precede neurological manifestations. It would be interesting to try whether therapy applied in this early stage would be effective."} {"id": "PMID:1256635", "title": "[Subarachnoid hemorrhage from ruptured aneurysm in the course of pregnancy].", "content": "The authors report a case of subarachnoid haemorrhage from a ruptured aneurysm of the left internal carotid artery at the site of branching-off of the ophthalmic artery in a patient with advanced pregnancy. Indications and contraindications to surgical treatment in pregnancy are discussed. The case and follow-up are described.", "contents": "[Subarachnoid hemorrhage from ruptured aneurysm in the course of pregnancy]. The authors report a case of subarachnoid haemorrhage from a ruptured aneurysm of the left internal carotid artery at the site of branching-off of the ophthalmic artery in a patient with advanced pregnancy. Indications and contraindications to surgical treatment in pregnancy are discussed. The case and follow-up are described."} {"id": "PMID:1256636", "title": "[Diagnosis of 3-level lumbar nucleus pulposus prolapse].", "content": "Clinical investigations and plain film of the spine are not sufficient for diagnosis of three-level lumbar nucleus pulposus prolapse. Contrast investigations, especially radiculography with television monitoring, are particularly suitable for demonstration of multiple prolapses. In a material of 730 cases two-level prolapse was found in about 12% of cases and three-level prolapse in about 0.5% of cases and this suggests that radiculography should be carried out routinely before each operation for lumbar nucleus pulposus prolapse.", "contents": "[Diagnosis of 3-level lumbar nucleus pulposus prolapse]. Clinical investigations and plain film of the spine are not sufficient for diagnosis of three-level lumbar nucleus pulposus prolapse. Contrast investigations, especially radiculography with television monitoring, are particularly suitable for demonstration of multiple prolapses. In a material of 730 cases two-level prolapse was found in about 12% of cases and three-level prolapse in about 0.5% of cases and this suggests that radiculography should be carried out routinely before each operation for lumbar nucleus pulposus prolapse."} {"id": "PMID:1256644", "title": "Posterior fossa subdural hematoma demonstrated by vertebral angiography.", "content": "A case of spontaneous posterior fossa subdural hematoma secondary to anticoagulation therapy with definitive diagnosis made by vertebral angiography is reported. Vertebral angiographic findings are illustrated and demonstrate primarily mass effect from posterior compartment of posterior fossa and avascular area. Carotid angiography did not show hydrocephalus. A review of the literature was made and this appears to be the first reported case in which a posterior fossa subdural hematoma has been diagnosed by vertebral angiography.", "contents": "Posterior fossa subdural hematoma demonstrated by vertebral angiography. A case of spontaneous posterior fossa subdural hematoma secondary to anticoagulation therapy with definitive diagnosis made by vertebral angiography is reported. Vertebral angiographic findings are illustrated and demonstrate primarily mass effect from posterior compartment of posterior fossa and avascular area. Carotid angiography did not show hydrocephalus. A review of the literature was made and this appears to be the first reported case in which a posterior fossa subdural hematoma has been diagnosed by vertebral angiography."} {"id": "PMID:1256645", "title": "Location of the \"zero zone\" and its role in the pathogenesis of cervical spondylosis.", "content": "Significant correlation between the location of the \"zero zone\" and spondylosis was found in the cervical spine. The possible role of the zero zone in the development of spondylosis is suggested and the deleterious effect of counteracting forces as compared with a unidirectional traction is stressed.", "contents": "Location of the \"zero zone\" and its role in the pathogenesis of cervical spondylosis. Significant correlation between the location of the \"zero zone\" and spondylosis was found in the cervical spine. The possible role of the zero zone in the development of spondylosis is suggested and the deleterious effect of counteracting forces as compared with a unidirectional traction is stressed."} {"id": "PMID:1256646", "title": "Cerebral cortical arteries in the diagnosis of epidural hematoma.", "content": "Review of cerebral arteriograms of all our patients [19] with epidural hematoma over a 2 year period revealed evidence of localized extrinsic compression of the cerebral cortex in all cases. This finding, although not as specific as those previously described for epidural hematoma, was strongly suggestive. A 2 year prospective study was then initiated employing internal, rather than common carotid arteriography, because opacification of the external carotid artery is not necessary for evaluation of cortical compression. In this study, which consisted of 21 patients, epidural hematoma was correctly diagnosed in all, relying primarily on signs of localized extrinisic cerebral cortical compression. No epidural hematoma was misinterpreted as being a subdural hematoma or an intracerebral injury, and all epidural hematomas that were present were diagnosed correctly. We conclude that internal carotid arteriography is a sensitive method for diagnosing epidural hematoma. The signs of extrinsic cortical compression should be emphasized in the interpretation of arteriograms of patients with head injuries whether the internal or the common carotid artery is injected.", "contents": "Cerebral cortical arteries in the diagnosis of epidural hematoma. Review of cerebral arteriograms of all our patients [19] with epidural hematoma over a 2 year period revealed evidence of localized extrinsic compression of the cerebral cortex in all cases. This finding, although not as specific as those previously described for epidural hematoma, was strongly suggestive. A 2 year prospective study was then initiated employing internal, rather than common carotid arteriography, because opacification of the external carotid artery is not necessary for evaluation of cortical compression. In this study, which consisted of 21 patients, epidural hematoma was correctly diagnosed in all, relying primarily on signs of localized extrinisic cerebral cortical compression. No epidural hematoma was misinterpreted as being a subdural hematoma or an intracerebral injury, and all epidural hematomas that were present were diagnosed correctly. We conclude that internal carotid arteriography is a sensitive method for diagnosing epidural hematoma. The signs of extrinsic cortical compression should be emphasized in the interpretation of arteriograms of patients with head injuries whether the internal or the common carotid artery is injected."} {"id": "PMID:1256647", "title": "Cavum veli interpositi. Roentgen anatomy - pathology and physiology.", "content": "158 pneumoencephalographies of infants less than 2 years old were examined and 53 of them had a large cavum veli interpositi. A neuroradiological description of this cistern is given and a comparison made with injected anatomical specimens. A statistical comparison with 105 pneumoencephalographies without a cavum veli interpositi does not shown any correlation between the presence of this cistern and pathological conditions. This investigation indicates that a large cavum veli interpositi in the newborn has no relation to hydrocephalus or cerebral atrophy. The younger the child, the more frequent is the presence of this cistern, especially under eight months of age.", "contents": "Cavum veli interpositi. Roentgen anatomy - pathology and physiology. 158 pneumoencephalographies of infants less than 2 years old were examined and 53 of them had a large cavum veli interpositi. A neuroradiological description of this cistern is given and a comparison made with injected anatomical specimens. A statistical comparison with 105 pneumoencephalographies without a cavum veli interpositi does not shown any correlation between the presence of this cistern and pathological conditions. This investigation indicates that a large cavum veli interpositi in the newborn has no relation to hydrocephalus or cerebral atrophy. The younger the child, the more frequent is the presence of this cistern, especially under eight months of age."} {"id": "PMID:1256648", "title": "Angiographic demonstration of a trigeminal neurinoma.", "content": "The case of a young man with a trigeminal neurinoma arising from the cerebellopontine angle and extending to the Gasserion ganglion is presented and the angiographic findings are described.", "contents": "Angiographic demonstration of a trigeminal neurinoma. The case of a young man with a trigeminal neurinoma arising from the cerebellopontine angle and extending to the Gasserion ganglion is presented and the angiographic findings are described."} {"id": "PMID:1256670", "title": "[Histological findings in parabiosis with crossed digestive tubes].", "content": "Microscopic examination of organs from outbred and inbred rats used in 5 groups for experiments in parabiosis with and without crossing of the digestive tubes and pseudoparabiosis showed that skin junctions soon became dehiscent, with boundary furrows tendings to separate the animals, in outbred rats, whereas continuity was not lost throughout the experiment in inbred rats, whereas continuity was not lost throughout the experiment in inbred animals. Juncture with abundant connective tissue rich in small-cell infiltrates was noted in intestinal anastomoses between outbreds, followed by dehiscence or incomplte junction. In inbred animals, junctions persisted till death; these were usually less abud nant than in anastomoses after section in the same animal. Serious steatoticonecrotic liver and amyloidotic kidney alterations were noted in all animals in parabiosis and pseudoparabiosis. These were more marker in inbred animals and appeared to have been responsible for death in cases where dehiscence and peritonitis did not take place. These histopathological pictures - also noted in inbred rats in pseudoparabiosis (i. e. kept together by nylon nets only) - make it impossible to say whether crossing of the digestive tubes is per se a cause of lesions. The experimentation of another parabiosis technique is proposed.", "contents": "[Histological findings in parabiosis with crossed digestive tubes]. Microscopic examination of organs from outbred and inbred rats used in 5 groups for experiments in parabiosis with and without crossing of the digestive tubes and pseudoparabiosis showed that skin junctions soon became dehiscent, with boundary furrows tendings to separate the animals, in outbred rats, whereas continuity was not lost throughout the experiment in inbred rats, whereas continuity was not lost throughout the experiment in inbred animals. Juncture with abundant connective tissue rich in small-cell infiltrates was noted in intestinal anastomoses between outbreds, followed by dehiscence or incomplte junction. In inbred animals, junctions persisted till death; these were usually less abud nant than in anastomoses after section in the same animal. Serious steatoticonecrotic liver and amyloidotic kidney alterations were noted in all animals in parabiosis and pseudoparabiosis. These were more marker in inbred animals and appeared to have been responsible for death in cases where dehiscence and peritonitis did not take place. These histopathological pictures - also noted in inbred rats in pseudoparabiosis (i. e. kept together by nylon nets only) - make it impossible to say whether crossing of the digestive tubes is per se a cause of lesions. The experimentation of another parabiosis technique is proposed."} {"id": "PMID:1256665", "title": "[Emergency surgery for traumatic diaphragmatic hernia. Treatment of 2 cases in children].", "content": "Two cases of tra-matic diaphragmatic hernia, observed in children, are reported. The pathologenesis and therapy are discussed.", "contents": "[Emergency surgery for traumatic diaphragmatic hernia. Treatment of 2 cases in children]. Two cases of tra-matic diaphragmatic hernia, observed in children, are reported. The pathologenesis and therapy are discussed."} {"id": "PMID:1256671", "title": "[Thyroid carcinoma in the young age].", "content": "Thyroid carcinoma in the young is relatively benign. Lymph node, lung and bone metastases are very frequent. This sets a premium on early diagnosis and at the same time complicates the choice of management. These wellcombined surgical and radiation treatment is therefore recommended.", "contents": "[Thyroid carcinoma in the young age]. Thyroid carcinoma in the young is relatively benign. Lymph node, lung and bone metastases are very frequent. This sets a premium on early diagnosis and at the same time complicates the choice of management. These wellcombined surgical and radiation treatment is therefore recommended."} {"id": "PMID:1256672", "title": "[Pancreatic diseases with pleuropulmonary complications of surgical significance].", "content": "It is well known that a pleuropneumopathy brought on by local action of biochemical nature (amylase) can occur in the course of quiescent or unknown pancreatitis. The literature on the subject was therefore examined with respect to abdominothoracic diffusion of the pancreatic excretion. Also examined were indications for surgery in the unusual complications which may arise, often with dramatic emergency (acute abdomen in sufferers from slight persistent pleural effusion; pleuropulmonary perforative syndrome in be course of quite stabilized chronic pancreatitis). Personal experience with four successfully treated cases is reported. The literature contains only sporadic examples and some remarks and deductions are made with regard to the controversial ways of amylasic abdominothoracic transfer.", "contents": "[Pancreatic diseases with pleuropulmonary complications of surgical significance]. It is well known that a pleuropneumopathy brought on by local action of biochemical nature (amylase) can occur in the course of quiescent or unknown pancreatitis. The literature on the subject was therefore examined with respect to abdominothoracic diffusion of the pancreatic excretion. Also examined were indications for surgery in the unusual complications which may arise, often with dramatic emergency (acute abdomen in sufferers from slight persistent pleural effusion; pleuropulmonary perforative syndrome in be course of quite stabilized chronic pancreatitis). Personal experience with four successfully treated cases is reported. The literature contains only sporadic examples and some remarks and deductions are made with regard to the controversial ways of amylasic abdominothoracic transfer."} {"id": "PMID:1256666", "title": "[Ceporex in the treatment of closed injuries of the thorax].", "content": "The effectiveness of antibiotic therapy with Cefaloridine in 49 patients with thoracic trauma is presented and the results obtained evaluated.", "contents": "[Ceporex in the treatment of closed injuries of the thorax]. The effectiveness of antibiotic therapy with Cefaloridine in 49 patients with thoracic trauma is presented and the results obtained evaluated."} {"id": "PMID:1256667", "title": "[Extracorporeal circulation in homologous and heterologous isolated liver in the depurative treatment of prolonged limb ischemia. Experimental research].", "content": "Preliminary experiments in extracorporeal cleansing of long ischaemic limbs with isolated liver prior to re-establishment of normal circulation are described. The absence of cases of renal block and the survival of all the animals so treated offer encouragement for the prosecution of this line of investigation.", "contents": "[Extracorporeal circulation in homologous and heterologous isolated liver in the depurative treatment of prolonged limb ischemia. Experimental research]. Preliminary experiments in extracorporeal cleansing of long ischaemic limbs with isolated liver prior to re-establishment of normal circulation are described. The absence of cases of renal block and the survival of all the animals so treated offer encouragement for the prosecution of this line of investigation."} {"id": "PMID:1256673", "title": "[Thoracic injuries and resuscitation. Case reports and critical review].", "content": "A series of 68 chest injuries treated at the Resuscitation and Intensive Care Unit. S. Orsola Policlinic, Bologna, between May 1967 and December 1973 is presented. Treatment was given by the staff of the anaesthesia and resuscitation service and the chest surgery section, 2nd Surgical Clinic, University of Bologna. The types of case observed and the treatment methods employed are bierfly explained, together with the clinical and statistical data. Emphasis is laid on the relation between clinical course and blood gas values. The value of tracheostomy and protracted intubation is discussed, together with the utility of antalgic and psychosedative management. The increased frequency of bronchopneumonic complications is noted. Encouraging results obtained by surgical stabilisation of movable flaps by means of Kirschner wires are reported. While this method admittedly requires thoracotomy, this in itself has the advantage of enabling existing pleural and pulmonary lesions to be repaired.", "contents": "[Thoracic injuries and resuscitation. Case reports and critical review]. A series of 68 chest injuries treated at the Resuscitation and Intensive Care Unit. S. Orsola Policlinic, Bologna, between May 1967 and December 1973 is presented. Treatment was given by the staff of the anaesthesia and resuscitation service and the chest surgery section, 2nd Surgical Clinic, University of Bologna. The types of case observed and the treatment methods employed are bierfly explained, together with the clinical and statistical data. Emphasis is laid on the relation between clinical course and blood gas values. The value of tracheostomy and protracted intubation is discussed, together with the utility of antalgic and psychosedative management. The increased frequency of bronchopneumonic complications is noted. Encouraging results obtained by surgical stabilisation of movable flaps by means of Kirschner wires are reported. While this method admittedly requires thoracotomy, this in itself has the advantage of enabling existing pleural and pulmonary lesions to be repaired."} {"id": "PMID:1256668", "title": "[Selective anterior vagotomy of the duodenum. Propositions, technics and experimental results].", "content": "Previous studies have demonstrated that changes in endoduodenal pressure may cause pancreatic alterations in biliary diseases. Anterior selective vagotomy of the duodenum was devised to reduce duodenal motility. An experimental study showed that such a surgical procedure is followed by a marked decrease in the overall duodenal kinesis, with disappearance of the highest pressure peaks.", "contents": "[Selective anterior vagotomy of the duodenum. Propositions, technics and experimental results]. Previous studies have demonstrated that changes in endoduodenal pressure may cause pancreatic alterations in biliary diseases. Anterior selective vagotomy of the duodenum was devised to reduce duodenal motility. An experimental study showed that such a surgical procedure is followed by a marked decrease in the overall duodenal kinesis, with disappearance of the highest pressure peaks."} {"id": "PMID:1256674", "title": "[Prevention of hemorrhagic complications following cardiopulmonary bypass].", "content": "Isolated primary fibrinolysis following cardiopulmonary bypass was fully prevented by using a modern washing technique for the reusable metal parts of the extracorporeal circuit: immersion in 20% caustic soda for 4 hr and in a detergent solution for a further 4 hr prior to rinsing and sterilisation. Reduction of bleeding from 558 to 465 cc/m2 was attributable an improved perfusion technique, early diagnosis and radical cleaning of the circuit. The disappearance of fibrinolysis, however, was entirely brought about by more thorough cleansing of the reusable metal parts.", "contents": "[Prevention of hemorrhagic complications following cardiopulmonary bypass]. Isolated primary fibrinolysis following cardiopulmonary bypass was fully prevented by using a modern washing technique for the reusable metal parts of the extracorporeal circuit: immersion in 20% caustic soda for 4 hr and in a detergent solution for a further 4 hr prior to rinsing and sterilisation. Reduction of bleeding from 558 to 465 cc/m2 was attributable an improved perfusion technique, early diagnosis and radical cleaning of the circuit. The disappearance of fibrinolysis, however, was entirely brought about by more thorough cleansing of the reusable metal parts."} {"id": "PMID:1256676", "title": "[Treatment of hydatid cysts of the liver perforated into the intrahepatic bile ducts].", "content": "After recalling the latest finding on the pathological anatomy, physiopathology, symptomatology, diagnosis and surgical therapy of hepatic echinococcus with intrahepatic bile duct fistulas, the personal series and that of the Palermo Surgical Pathology School is illustrated. These series included 12 patients. The surgery employed is analysed and results obtained reported. It is concluded that modern diagnostic methods, particularly intraoperatory, the new radical surgery techniques, and the improved post-operative assistance offer better chances of success in this condition, reducing both mortality and postoperative complications.", "contents": "[Treatment of hydatid cysts of the liver perforated into the intrahepatic bile ducts]. After recalling the latest finding on the pathological anatomy, physiopathology, symptomatology, diagnosis and surgical therapy of hepatic echinococcus with intrahepatic bile duct fistulas, the personal series and that of the Palermo Surgical Pathology School is illustrated. These series included 12 patients. The surgery employed is analysed and results obtained reported. It is concluded that modern diagnostic methods, particularly intraoperatory, the new radical surgery techniques, and the improved post-operative assistance offer better chances of success in this condition, reducing both mortality and postoperative complications."} {"id": "PMID:1256677", "title": "Gastric antrum and dumping syndrome. Possible pathogenetic correlations.", "content": "On the basis of the observation that the dumping syndrome is seen very rarely now compared to the past, experimental and clinical research was carried out with a view to explaining this phenomenon. These studies showed that it is possible that the gastric antrum plays a basic role in the pathogenesis of the dumping syndrome.", "contents": "Gastric antrum and dumping syndrome. Possible pathogenetic correlations. On the basis of the observation that the dumping syndrome is seen very rarely now compared to the past, experimental and clinical research was carried out with a view to explaining this phenomenon. These studies showed that it is possible that the gastric antrum plays a basic role in the pathogenesis of the dumping syndrome."} {"id": "PMID:1256678", "title": "[Results with arteriovenous fistulae in periodic haemodialysis].", "content": "Personal experience regarding 92 arteriovenous fistuale carried for the application of the artificial kidney in 70 patients is described. The technical technique is explained and haemodynamic considerations in support of a preference for end-to-end anastomosis are illustrated. A critical assessment is made of the reasons for failure and their prognostic significance as far as subsequent operation is concerned.", "contents": "[Results with arteriovenous fistulae in periodic haemodialysis]. Personal experience regarding 92 arteriovenous fistuale carried for the application of the artificial kidney in 70 patients is described. The technical technique is explained and haemodynamic considerations in support of a preference for end-to-end anastomosis are illustrated. A critical assessment is made of the reasons for failure and their prognostic significance as far as subsequent operation is concerned."} {"id": "PMID:1256680", "title": "[Papillosphincteroplasty and wirsungsphincteroplasty. Immediate and late results].", "content": "Immediate and long-term results in 250 PSP operations associated with WSP in 116 cases are reported. Complications and failures are described and evaluated, while their causes and possible connection with the type of operation employed are explained. Examinations carried out in the assessment of long-term results are described and justified. It is felt that both operations are to be recommended. WSP, in particular, is considered a useful innovation in surgical repair of the bilopancreatic juncture.", "contents": "[Papillosphincteroplasty and wirsungsphincteroplasty. Immediate and late results]. Immediate and long-term results in 250 PSP operations associated with WSP in 116 cases are reported. Complications and failures are described and evaluated, while their causes and possible connection with the type of operation employed are explained. Examinations carried out in the assessment of long-term results are described and justified. It is felt that both operations are to be recommended. WSP, in particular, is considered a useful innovation in surgical repair of the bilopancreatic juncture."} {"id": "PMID:1256681", "title": "[Our experience with total gastrectomy for treatment of gastric carcinoma].", "content": "A personal series of cases in which surgical management was employed in the treatment of stomach cancers is presented. Total resection is recommended as a method of choice, followed by reconstruction of oesophago-intestinal continuity by interposing an excluded jejunal loop.", "contents": "[Our experience with total gastrectomy for treatment of gastric carcinoma]. A personal series of cases in which surgical management was employed in the treatment of stomach cancers is presented. Total resection is recommended as a method of choice, followed by reconstruction of oesophago-intestinal continuity by interposing an excluded jejunal loop."} {"id": "PMID:1256684", "title": "[Use of echography as a diagnostic aid in pediatric abdominal pathology].", "content": "Echotomography was used in the diagnosis of abdominal paediatric pathology and results compared with traditional methods of investigation. Out of 15 cases examined, echotomography proved its value in the location of the lesions and in the definition of their dimensions and structure.", "contents": "[Use of echography as a diagnostic aid in pediatric abdominal pathology]. Echotomography was used in the diagnosis of abdominal paediatric pathology and results compared with traditional methods of investigation. Out of 15 cases examined, echotomography proved its value in the location of the lesions and in the definition of their dimensions and structure."} {"id": "PMID:1256685", "title": "[Neuroblastoma. Clinical aspects and therapy].", "content": "A general account of questions relating to neuroblastoma is followed by the presentation of 53 personal cases observed between 1955 and 1974. Appraisal of the salient data offers information relating to prognosis and treatment in line with the more extensive series presented in the U.S. literature and elsewhere. Cases diagnosed and treated in the first year of life have a distinctly encouraging prognosis. It is felt that accurate clinical, radiological and laboratory screening should be relied upon in individual cases to decide whether or not surgical management is indicated, whereas the high rate of intra- and post-operative mortality would seem to militate against the resort to desperate attempts to achieve total extirpation, accompanied by damage to essential structures, especially since the pratical results achieved are no more than comparable with those offered by conservative surgery. It is hoped that a strip test suitable for use in routine practice will be evolved, bearing in mind the peculiar features of neuroblastomas.", "contents": "[Neuroblastoma. Clinical aspects and therapy]. A general account of questions relating to neuroblastoma is followed by the presentation of 53 personal cases observed between 1955 and 1974. Appraisal of the salient data offers information relating to prognosis and treatment in line with the more extensive series presented in the U.S. literature and elsewhere. Cases diagnosed and treated in the first year of life have a distinctly encouraging prognosis. It is felt that accurate clinical, radiological and laboratory screening should be relied upon in individual cases to decide whether or not surgical management is indicated, whereas the high rate of intra- and post-operative mortality would seem to militate against the resort to desperate attempts to achieve total extirpation, accompanied by damage to essential structures, especially since the pratical results achieved are no more than comparable with those offered by conservative surgery. It is hoped that a strip test suitable for use in routine practice will be evolved, bearing in mind the peculiar features of neuroblastomas."} {"id": "PMID:1256687", "title": "[Controlled clinical trial of 2-mercapto-propionyl-glycine in chronic hepatopathies].", "content": "A controlled clinical trial comparing 2-Mercapto-Priopionyl-Glycine (2-MPG) plus B12 vitamin with B12 vitamin alone in chronic liver disease has been conducted in seven hospitals in Italy. Patients were divided into two groups on the basis of liver histology; group I included 26 patients showing histological evidence for chronic persistent hepatitis (C.P.H.) (according to De Groote et al.) whereas group II consisted of 54 patients with chronic aggressive hepatitis (C.A.H.) or compensated liver cirrhosis. Patients of each group were randomly allocated to 2-MPG plus B12 vitamin, or to placebo plus B12 vitamin, in a double-blind way. The drug (or placebo) was diluted in 500 ml of 10% Levulose, and administered intravenously; 1000 gamma of B12 vitamin were added to each bottle. Patients in the 2-MPG group received 2.5 gms of the drug daily; the treatment lasted for 30 days. The following parameters were checked in all patients on admission, and repeated at the end of treatment: Serum bilirubin, serum Cholesterol, A.P., BSP retention, Prothrombin time, S-GOT, S-GPT, Gamma-GT, Total serum Protein, serum electrophoresis, Immunoglobulins. Patients given 2-MPG showed significant decreases of serum transaminases, and improvement of BSP retention.", "contents": "[Controlled clinical trial of 2-mercapto-propionyl-glycine in chronic hepatopathies]. A controlled clinical trial comparing 2-Mercapto-Priopionyl-Glycine (2-MPG) plus B12 vitamin with B12 vitamin alone in chronic liver disease has been conducted in seven hospitals in Italy. Patients were divided into two groups on the basis of liver histology; group I included 26 patients showing histological evidence for chronic persistent hepatitis (C.P.H.) (according to De Groote et al.) whereas group II consisted of 54 patients with chronic aggressive hepatitis (C.A.H.) or compensated liver cirrhosis. Patients of each group were randomly allocated to 2-MPG plus B12 vitamin, or to placebo plus B12 vitamin, in a double-blind way. The drug (or placebo) was diluted in 500 ml of 10% Levulose, and administered intravenously; 1000 gamma of B12 vitamin were added to each bottle. Patients in the 2-MPG group received 2.5 gms of the drug daily; the treatment lasted for 30 days. The following parameters were checked in all patients on admission, and repeated at the end of treatment: Serum bilirubin, serum Cholesterol, A.P., BSP retention, Prothrombin time, S-GOT, S-GPT, Gamma-GT, Total serum Protein, serum electrophoresis, Immunoglobulins. Patients given 2-MPG showed significant decreases of serum transaminases, and improvement of BSP retention."} {"id": "PMID:1256689", "title": "[Clinical studies of the effect of a phosphorylated glycoderivative in acute viral hepatitis].", "content": "Experimentation of two i.v. doses of a uridine-5-diphosphoglucose (UDPG) in 30 cases of acute viral hepatitis is reported. The therapeutic efficacy of the drug was assessed on qualitative and quantitative parameters indicative of liver distress. Statistically significant evidence was obtained of the efficacy of UDPG in acute and serious liver disease, and of the greater effectiveness of one of the two doses used. Excellent local and general tolerance was noted.", "contents": "[Clinical studies of the effect of a phosphorylated glycoderivative in acute viral hepatitis]. Experimentation of two i.v. doses of a uridine-5-diphosphoglucose (UDPG) in 30 cases of acute viral hepatitis is reported. The therapeutic efficacy of the drug was assessed on qualitative and quantitative parameters indicative of liver distress. Statistically significant evidence was obtained of the efficacy of UDPG in acute and serious liver disease, and of the greater effectiveness of one of the two doses used. Excellent local and general tolerance was noted."} {"id": "PMID:1256690", "title": "[Comparative evaluation of the therapeutic action and tolerance of diftalone and indomethacin in the long-term treatment of rheumatoid arthritis].", "content": "The therapeutic effectiveness and tolerability of diphthalone and indomethacine administered for long periods were compared in 10 patients suffering from rheumatoid arthritis in the active phase. Each patient was treated with one of the two drugs on a double blind basis. Diphthalone proved to be more active than indomethacine on morning stiffness and on hand grip strength. Diphthalone also produced fewer side effects. The differences indicated proved to be significant statistically.", "contents": "[Comparative evaluation of the therapeutic action and tolerance of diftalone and indomethacin in the long-term treatment of rheumatoid arthritis]. The therapeutic effectiveness and tolerability of diphthalone and indomethacine administered for long periods were compared in 10 patients suffering from rheumatoid arthritis in the active phase. Each patient was treated with one of the two drugs on a double blind basis. Diphthalone proved to be more active than indomethacine on morning stiffness and on hand grip strength. Diphthalone also produced fewer side effects. The differences indicated proved to be significant statistically."} {"id": "PMID:1256691", "title": "[A new drug combination for the treatment of non-tubercular acute and chronic bronchopneumopathies].", "content": "Good therapeutic results free of unwanted side-effects were observed in the management of acute and chronic non-tubercular bronchopneumopathies with an association of tetracyclin hydrochloride, proteolytic enzymes (trypsin and chymotrypsin), vanillic acid diethylamide and pyridophyllin.", "contents": "[A new drug combination for the treatment of non-tubercular acute and chronic bronchopneumopathies]. Good therapeutic results free of unwanted side-effects were observed in the management of acute and chronic non-tubercular bronchopneumopathies with an association of tetracyclin hydrochloride, proteolytic enzymes (trypsin and chymotrypsin), vanillic acid diethylamide and pyridophyllin."} {"id": "PMID:1256694", "title": "[Coloscopy in the diagnosis of inflammatory diseases of the large intestine].", "content": "The usefulness of coloscopy in the diagnosis of inflammatory disease of the large intestine is discussed. A nosological classification was obtained in 440/493 instances of inflammation noted in over 3000 coloscopies-on the basis of the clinical, radiological, endoscopic and histological findings. The endoscopic picture for each disease is described, with particular reference to the main features upon which correct differential diagnosis and classification depend. Coloscopy is virtually indispensable in obtaining a complete clinical study of inflammatory diseases of the colon.", "contents": "[Coloscopy in the diagnosis of inflammatory diseases of the large intestine]. The usefulness of coloscopy in the diagnosis of inflammatory disease of the large intestine is discussed. A nosological classification was obtained in 440/493 instances of inflammation noted in over 3000 coloscopies-on the basis of the clinical, radiological, endoscopic and histological findings. The endoscopic picture for each disease is described, with particular reference to the main features upon which correct differential diagnosis and classification depend. Coloscopy is virtually indispensable in obtaining a complete clinical study of inflammatory diseases of the colon."} {"id": "PMID:1256696", "title": "[Clinico-statistical studies of 700 cases of lymphopathy of various types. Nosological considerations].", "content": "A breakdown of the statistical data for 700 cases of lymphopathy was undertaken to how far each disease picture could be considered as a seperate entity or as part of a sub-class. It was found that two possibilities exist: a) there is a typical sub-class for this nosological category; b) two sub-classes can be formed, one of which covers paranormal situations, while the other includes cases presenting pathological parameter values. In either event, there remains a considerable fringe of atypical cases that cannot be included in any sub-class.", "contents": "[Clinico-statistical studies of 700 cases of lymphopathy of various types. Nosological considerations]. A breakdown of the statistical data for 700 cases of lymphopathy was undertaken to how far each disease picture could be considered as a seperate entity or as part of a sub-class. It was found that two possibilities exist: a) there is a typical sub-class for this nosological category; b) two sub-classes can be formed, one of which covers paranormal situations, while the other includes cases presenting pathological parameter values. In either event, there remains a considerable fringe of atypical cases that cannot be included in any sub-class."} {"id": "PMID:1256697", "title": "[Possibilities of metabolic endoradiotherapy with P32 in the prevention of osseous metastases from breast neoplasms. Note II].", "content": "To reach a definitive conclusion on the value of using 32P in the prophylaxis of bone metastases in association with surgical and traditional radiotherapeutic treatment, observations should be extended to a much greater number of cases. This notwithstanding, the results obtained justify this methodology based on continuous sustained, internal irradiation which would seem to make possible a diminution in the frequency of bone metastases in the early years of a delay in their onset.", "contents": "[Possibilities of metabolic endoradiotherapy with P32 in the prevention of osseous metastases from breast neoplasms. Note II]. To reach a definitive conclusion on the value of using 32P in the prophylaxis of bone metastases in association with surgical and traditional radiotherapeutic treatment, observations should be extended to a much greater number of cases. This notwithstanding, the results obtained justify this methodology based on continuous sustained, internal irradiation which would seem to make possible a diminution in the frequency of bone metastases in the early years of a delay in their onset."} {"id": "PMID:1256698", "title": "[Coloscopic characterization of polyposis of the large intestine. Macroscopic aspects and histological correlations].", "content": "On the basis of the usual macroscopic pathological descriptions, the possibility of characterizing endoscopically the various types of polypous proliferations in the large intestine is examined. The endoscopic parameters considered are described together with the histopathological findings incases of polyps observed over a period of 6 months. Comparison between presumed diagnosis formulated at coloscopic examination and final histological diagnosis shows a concordance of 80%. The usefulness of being able to give some indication regarding the type of nature of the polyps as early as endoscopy is stressed.", "contents": "[Coloscopic characterization of polyposis of the large intestine. Macroscopic aspects and histological correlations]. On the basis of the usual macroscopic pathological descriptions, the possibility of characterizing endoscopically the various types of polypous proliferations in the large intestine is examined. The endoscopic parameters considered are described together with the histopathological findings incases of polyps observed over a period of 6 months. Comparison between presumed diagnosis formulated at coloscopic examination and final histological diagnosis shows a concordance of 80%. The usefulness of being able to give some indication regarding the type of nature of the polyps as early as endoscopy is stressed."} {"id": "PMID:1256699", "title": "[Polycentric studies of idiopathic ulcerous rectocolitis and Crohn's disease of the colon].", "content": "An attempt is made to synthesize the experience of leading Italian Endoscopy Centres that concern themselves with problems of the colon. On the basis of a simple questionnaire, the series of 8 Endoscopy Centres have been collected. These number 6012 coloscopic examinations, 465 cases of Idiopathic Ulcerative Colitis and 149 cases of Crohn's Disease of the colon.", "contents": "[Polycentric studies of idiopathic ulcerous rectocolitis and Crohn's disease of the colon]. An attempt is made to synthesize the experience of leading Italian Endoscopy Centres that concern themselves with problems of the colon. On the basis of a simple questionnaire, the series of 8 Endoscopy Centres have been collected. These number 6012 coloscopic examinations, 465 cases of Idiopathic Ulcerative Colitis and 149 cases of Crohn's Disease of the colon."} {"id": "PMID:1256700", "title": "[Non-ketosic hyperosmolar hyperglycemic coma. Case reports and therapeutic consideration].", "content": "Non-ketonic hyperosmolar hyperglycaemic coma (N.K.H.H.C.) is by no means uncommon in diabetes. Its picture includes sensorial depression, hyperglycaemia, hyperazotemia, marked dehydration and plasma hyperosmolarity. It is mostly found in elderly subjects with non-serious diabetes. Reference is made to 6 personal cases observed during a period of 14 months. The incidence of N.K.H.H.C. noted during this period was 2.2%; this was higher than that of ketoacidotic coma. Two patients died from hypovolaemic shock and one from septic complications. Three survived the episode. Treatment was based on three main points: high doses of insulin, though less than those employed for equal blood sugar levels in cases of ketoacidotic coma, hypotonic saline solutions, and correction of electrolyte imbalance. It is hoped that improved knowledge of the syndrome and, more particularly, earlier diagnosis and treatment, with lead to a reduction in the ta 50% mortality present associated with the disease.", "contents": "[Non-ketosic hyperosmolar hyperglycemic coma. Case reports and therapeutic consideration]. Non-ketonic hyperosmolar hyperglycaemic coma (N.K.H.H.C.) is by no means uncommon in diabetes. Its picture includes sensorial depression, hyperglycaemia, hyperazotemia, marked dehydration and plasma hyperosmolarity. It is mostly found in elderly subjects with non-serious diabetes. Reference is made to 6 personal cases observed during a period of 14 months. The incidence of N.K.H.H.C. noted during this period was 2.2%; this was higher than that of ketoacidotic coma. Two patients died from hypovolaemic shock and one from septic complications. Three survived the episode. Treatment was based on three main points: high doses of insulin, though less than those employed for equal blood sugar levels in cases of ketoacidotic coma, hypotonic saline solutions, and correction of electrolyte imbalance. It is hoped that improved knowledge of the syndrome and, more particularly, earlier diagnosis and treatment, with lead to a reduction in the ta 50% mortality present associated with the disease."} {"id": "PMID:1256723", "title": "Clinical findings and hormonal responses in patients with polycystic ovarian disease with normal versus elevated LH levels.", "content": "The clinical features, ovarian pathology, and hormonal responses to dexamethasone (Dex), Dex + ethinyl estradiol (EE), and Dex + hCG were compared in 5 women with polycystic ovarian disease (PCOD) who have normal 24-hr urinary luteinizing hormone (LH levels to 5 who had elevated urinary LH levels. No differences were noted in the clinical features. There was no correlation between ovary size and LH levels. Three in the normal-LH group had hyperthecosis. Plasma androstenedione (A) was more frequently elevated in the high-LH group. Dex + EE markedly increased LH secretion in the high-LH group, suggesting increased responsiveness of the positive feedback control mechanism of LH secretion in the high-LH group. There was a greater response of A, testosterone (T), and 17-ketosteroids to Dex + hCG in the normal-LH group. Those with high-LH levels did not exhibit a significant increase in A, T, and 17-KS with hCG. The limitations and usefulness of the Dex + hCG test are discussed. The hypothesis is advanced that the increased LH secretion in the high-LH group is due at least in part to positive feedback resulting from the increased A levels. The amount of 17beta-oxidoreductase activity in the ovary may influence LH secretion in PCOD.", "contents": "Clinical findings and hormonal responses in patients with polycystic ovarian disease with normal versus elevated LH levels. The clinical features, ovarian pathology, and hormonal responses to dexamethasone (Dex), Dex + ethinyl estradiol (EE), and Dex + hCG were compared in 5 women with polycystic ovarian disease (PCOD) who have normal 24-hr urinary luteinizing hormone (LH levels to 5 who had elevated urinary LH levels. No differences were noted in the clinical features. There was no correlation between ovary size and LH levels. Three in the normal-LH group had hyperthecosis. Plasma androstenedione (A) was more frequently elevated in the high-LH group. Dex + EE markedly increased LH secretion in the high-LH group, suggesting increased responsiveness of the positive feedback control mechanism of LH secretion in the high-LH group. There was a greater response of A, testosterone (T), and 17-ketosteroids to Dex + hCG in the normal-LH group. Those with high-LH levels did not exhibit a significant increase in A, T, and 17-KS with hCG. The limitations and usefulness of the Dex + hCG test are discussed. The hypothesis is advanced that the increased LH secretion in the high-LH group is due at least in part to positive feedback resulting from the increased A levels. The amount of 17beta-oxidoreductase activity in the ovary may influence LH secretion in PCOD."} {"id": "PMID:1256724", "title": "Laparoscopy and the infertility evaluation.", "content": "Results of laparoscopic evaluation of 112 infertile women are presented. Laparoscopy performed prior to comtemplated fallopian tube reconstructive surgery changed the plan of management of 41% of 44 cases. Of 64 women with a normal hysterogram, 58% were found to have evidence of pelvic disease, and 47% had changes in their management based on the findings at laparoscopy. The specific indications and timing of laparoscopy in relation to the remainder of the infertility evaluation are discussed.", "contents": "Laparoscopy and the infertility evaluation. Results of laparoscopic evaluation of 112 infertile women are presented. Laparoscopy performed prior to comtemplated fallopian tube reconstructive surgery changed the plan of management of 41% of 44 cases. Of 64 women with a normal hysterogram, 58% were found to have evidence of pelvic disease, and 47% had changes in their management based on the findings at laparoscopy. The specific indications and timing of laparoscopy in relation to the remainder of the infertility evaluation are discussed."} {"id": "PMID:1256725", "title": "Induction of an LH surge with estradiol benzoate. A clinical test of pituitary-hypothalamic axis competence.", "content": "Intramuscular injection of 6.6 mg of estradiol benzoate (EB) in oil was used in 34 women as a test of the ability of the pituitary-hypothalamic axis to produce a gonadotropin surge (positive-feedback response). These responses were compared to Clomid responses. All of the normal cycling women, two-thirds of oligo-ovulatory but menstruating women, and one-third of amenorrheic women had LH surges to EB challenge. Estradiol benzoate is a more specific test of positive feedback response than Clomid. It also may be effective in inducing ovulation in some amenorrheic patients refractory to Clomid treatment.", "contents": "Induction of an LH surge with estradiol benzoate. A clinical test of pituitary-hypothalamic axis competence. Intramuscular injection of 6.6 mg of estradiol benzoate (EB) in oil was used in 34 women as a test of the ability of the pituitary-hypothalamic axis to produce a gonadotropin surge (positive-feedback response). These responses were compared to Clomid responses. All of the normal cycling women, two-thirds of oligo-ovulatory but menstruating women, and one-third of amenorrheic women had LH surges to EB challenge. Estradiol benzoate is a more specific test of positive feedback response than Clomid. It also may be effective in inducing ovulation in some amenorrheic patients refractory to Clomid treatment."} {"id": "PMID:1256726", "title": "Uterine anomalies. Frequency of diagnosis and associated obstetric complications.", "content": "Uterine anomalies are associated with an increase in cases of breech presentation, premature labor, abnormal presentation with dystocia, and the necessity for cesarean section. The yearly frequency of diagnosis of an anomaly has varied from 0.06 to 0.48 at this medical center depending on the physician's clinical suspicion. Thus, if the true incidence and the decrease of obstetric complications are to be accomplished, an increased interest in diagnosing uterine anomalies is essential.", "contents": "Uterine anomalies. Frequency of diagnosis and associated obstetric complications. Uterine anomalies are associated with an increase in cases of breech presentation, premature labor, abnormal presentation with dystocia, and the necessity for cesarean section. The yearly frequency of diagnosis of an anomaly has varied from 0.06 to 0.48 at this medical center depending on the physician's clinical suspicion. Thus, if the true incidence and the decrease of obstetric complications are to be accomplished, an increased interest in diagnosing uterine anomalies is essential."} {"id": "PMID:1256727", "title": "Maternal mortality in an urban hospital. A fifteen-year survey.", "content": "A 15-year survey of maternal mortality in a large urban hospital revealed an overall rate of 2.95 deaths per 10,000 pregnancies (3.44 per 10,000 live births), representing 31 maternal deaths among approximately 105,000 deliveries and spontaneous and therapeutic abortions. This rate showed marked improvement during the 15-year period, ie, 6.56 per 10,000 pregnancies for the first 5 years as compared to only 1.37 per 10,000 pregnancies for the last 10 years. In contrast to the classic triad of causes of maternal death--toxemia, hemorrhage, and spesis--the principal cause of death in this series was amniotic fluid embolism. Other aspects of the causes of death and of the findings are discussed. Among the 32 fetuses, total fetal wastage was 63%, with a neonatal mortality of 8% and a fetal mortality of 46%.", "contents": "Maternal mortality in an urban hospital. A fifteen-year survey. A 15-year survey of maternal mortality in a large urban hospital revealed an overall rate of 2.95 deaths per 10,000 pregnancies (3.44 per 10,000 live births), representing 31 maternal deaths among approximately 105,000 deliveries and spontaneous and therapeutic abortions. This rate showed marked improvement during the 15-year period, ie, 6.56 per 10,000 pregnancies for the first 5 years as compared to only 1.37 per 10,000 pregnancies for the last 10 years. In contrast to the classic triad of causes of maternal death--toxemia, hemorrhage, and spesis--the principal cause of death in this series was amniotic fluid embolism. Other aspects of the causes of death and of the findings are discussed. Among the 32 fetuses, total fetal wastage was 63%, with a neonatal mortality of 8% and a fetal mortality of 46%."} {"id": "PMID:1256728", "title": "Predictive value of human placental lactogen determinations in pregnancy.", "content": "The relation of human placental lactogen (hPL) levels to pregnancy outcome was studied in normal and preeclamptic pregnancies, hPL determinations were performed between 38 and 44 weeks of gestation, and the results were compared with birthweight and Apgar scores in three groups. The results of hPL determinations permitted prediction of intrauterine growth retardation in all except 2 patients. The value of hPL measurement as a screening test in pregnancy is noted.", "contents": "Predictive value of human placental lactogen determinations in pregnancy. The relation of human placental lactogen (hPL) levels to pregnancy outcome was studied in normal and preeclamptic pregnancies, hPL determinations were performed between 38 and 44 weeks of gestation, and the results were compared with birthweight and Apgar scores in three groups. The results of hPL determinations permitted prediction of intrauterine growth retardation in all except 2 patients. The value of hPL measurement as a screening test in pregnancy is noted."} {"id": "PMID:1256729", "title": "Human placental lactogen and intrauterine growth retardation.", "content": "Serum human placental lactogen levels were measured after 36 weeks' gestation in 264 serum samples from 109 women with normal pregnancies and in 137 serum samples from 70 women with pregnancies complicated by fetal intrauterine growth retardation (IGR). The fetal and placental weights were significantly lower in the IGR groups while the maternal ages were not different. There was a significantly lower hPL value at each week from 36 to 41 (except for the 39th) in the IGR group. Sixty percent of the women with IGR had hPL values less than 6 mug/ml, and 18.6% were less than 4 mug/ml. It is suggested that a low serum hPL value obtained during the last month of pregnancy should alert the physician to the possibility of intrauterine problems, including IGR.", "contents": "Human placental lactogen and intrauterine growth retardation. Serum human placental lactogen levels were measured after 36 weeks' gestation in 264 serum samples from 109 women with normal pregnancies and in 137 serum samples from 70 women with pregnancies complicated by fetal intrauterine growth retardation (IGR). The fetal and placental weights were significantly lower in the IGR groups while the maternal ages were not different. There was a significantly lower hPL value at each week from 36 to 41 (except for the 39th) in the IGR group. Sixty percent of the women with IGR had hPL values less than 6 mug/ml, and 18.6% were less than 4 mug/ml. It is suggested that a low serum hPL value obtained during the last month of pregnancy should alert the physician to the possibility of intrauterine problems, including IGR."} {"id": "PMID:1256730", "title": "Concurrent use of prostaglandin F2alpha and laminaria tents for induction of midtrimester abortion.", "content": "One hundred sixteen women between 14 and 20 weeks of gestation were aborted with a combined regimen of intraamniotic prostaglandin F2alpha (PGF2alpha) and intracervical laminaria. Complications among these women were compared to those among 122 patients who aborted after PGF2alpha administration only. Shorter intervals between initiation and completion of abortion were observed in nulliparous women treated with the combined regimen than in nulliparous women treated with PGF2alpha only. In parous patients, the use of laminaria did not shorten the interval from initiation to completion of abortion. A decrease of the hematocrit in excess of 5 points and periabortal infection requiring antibiotic therapy occurred with similar frequency in both treatment groups. However, with the combined regimen no cervical tears were observed in nulliparous patients, and fewer women failed to abort within 48 hours.", "contents": "Concurrent use of prostaglandin F2alpha and laminaria tents for induction of midtrimester abortion. One hundred sixteen women between 14 and 20 weeks of gestation were aborted with a combined regimen of intraamniotic prostaglandin F2alpha (PGF2alpha) and intracervical laminaria. Complications among these women were compared to those among 122 patients who aborted after PGF2alpha administration only. Shorter intervals between initiation and completion of abortion were observed in nulliparous women treated with the combined regimen than in nulliparous women treated with PGF2alpha only. In parous patients, the use of laminaria did not shorten the interval from initiation to completion of abortion. A decrease of the hematocrit in excess of 5 points and periabortal infection requiring antibiotic therapy occurred with similar frequency in both treatment groups. However, with the combined regimen no cervical tears were observed in nulliparous patients, and fewer women failed to abort within 48 hours."} {"id": "PMID:1256731", "title": "Acquired hypertrichosis lanuginosa associated with endometrial malignancy.", "content": "A 46-year-old nulligravida complained of the recent development of an erythematous skin eruption and fine blond hair over her face. These complaints appeared to be symptoms of acquired hypertrichosis lanuginosa, which may be associated with malignancy. The patient was found to have an endometrial adenocarcinoma with nodal metastases and was treated with hysterectomy and irradiation. Eighteen months later there was no evidence of the cancer, and the lanugo hairs had vanished. This is the first known instance of hypertrichosis lanuginosa associated with a gynecologic cancer and the first ever observed in which the lanugo hairs disappeared after cancer therapy.", "contents": "Acquired hypertrichosis lanuginosa associated with endometrial malignancy. A 46-year-old nulligravida complained of the recent development of an erythematous skin eruption and fine blond hair over her face. These complaints appeared to be symptoms of acquired hypertrichosis lanuginosa, which may be associated with malignancy. The patient was found to have an endometrial adenocarcinoma with nodal metastases and was treated with hysterectomy and irradiation. Eighteen months later there was no evidence of the cancer, and the lanugo hairs had vanished. This is the first known instance of hypertrichosis lanuginosa associated with a gynecologic cancer and the first ever observed in which the lanugo hairs disappeared after cancer therapy."} {"id": "PMID:1256733", "title": "An improved data display system for fetal heart rate monitoring.", "content": "Fetal heart rate (FHR) monitor records, particularly those derived from external sensors, may contain artifactual information closely resembling true FHR patterns. Additional machine-determined information may be used to help discriminate these data. Present commercial systems for indicating potentially artifactual FHR modify the FHR display, and this tends to cause the physician to ignore the absence of data or annoy him by obliterating some useful as well as potentialy useless information. Therefore, we chose to put the information that the data may be artifactual on another channel and allow the physician, rather than the instrument, to modify the interpretation of the FHR as necessary. A computer study was made of the characteristics of FHR beat-to-beat changes during poor signal to determine the most appropriate criteria for indicating when the FHR record is highly likely to be artifactual. Unphysiologic, erratic FHR changes are easily flagged by the presence of 3 serial beat-to-beat changes greater than 25 beats/min. Clinical testing demonstrated that this system allows the physician to better discriminate between valid and invalid data and increases the amount of usable data, particularly in active patients.", "contents": "An improved data display system for fetal heart rate monitoring. Fetal heart rate (FHR) monitor records, particularly those derived from external sensors, may contain artifactual information closely resembling true FHR patterns. Additional machine-determined information may be used to help discriminate these data. Present commercial systems for indicating potentially artifactual FHR modify the FHR display, and this tends to cause the physician to ignore the absence of data or annoy him by obliterating some useful as well as potentialy useless information. Therefore, we chose to put the information that the data may be artifactual on another channel and allow the physician, rather than the instrument, to modify the interpretation of the FHR as necessary. A computer study was made of the characteristics of FHR beat-to-beat changes during poor signal to determine the most appropriate criteria for indicating when the FHR record is highly likely to be artifactual. Unphysiologic, erratic FHR changes are easily flagged by the presence of 3 serial beat-to-beat changes greater than 25 beats/min. Clinical testing demonstrated that this system allows the physician to better discriminate between valid and invalid data and increases the amount of usable data, particularly in active patients."} {"id": "PMID:1256779", "title": "Characteristics of antifriction devices used for ski bindings.", "content": "These tests suggest that various antifriction devices do reduce the amount of torsion that can be transmitted to the skier's tibia during a slow twisting fall. It was shown that under various environmental conditions the antifriction devices are effective. Dirt negatively affected the performance of some devices. The importance of protecting bindings and antifriction devices from contamination cannot be overemphasized. It was shown that some antifriction devices perform better than others. In most instances the performance of the plate type of binding compares favorable with that of toe-heel bindings using antifriction devices. For the plate type of binding the dirt particularly had a detrimental effect. It should also be pointed out that these tests were run with one particular binding. These results would not necessarily be the same if the tests were conducted with another binding system. For instance, the limited motion of some of the antifriction devices (Lotork, Skidder) may impede their performance when used with bindings requiring a greater travel distance before release. The performance with other boot soles may be different from that with the particular boot sole used for these tests. Performance might be improved with a harder, smoother boot sole. Similarly, the effectiveness of the antifriction device may be reduced by the use of boot soles with a coarse pattern or relatively soft treads. In this test series a relatively small number of antifriction devices were evaluated. One should not presume that all devices will perform with equal effectiveness. Another factor, equally important, is the correction for the height of antifriction devices. Antifriction devices raise the boot sole from the ski surface, and if this change in height is not accounted for, the boot sole may effectively interfere with the operation of the toe or the heel unit. In summary, it can be stated that when properly applied and selected, antifriction devices make a significant contribution to skiing safety.", "contents": "Characteristics of antifriction devices used for ski bindings. These tests suggest that various antifriction devices do reduce the amount of torsion that can be transmitted to the skier's tibia during a slow twisting fall. It was shown that under various environmental conditions the antifriction devices are effective. Dirt negatively affected the performance of some devices. The importance of protecting bindings and antifriction devices from contamination cannot be overemphasized. It was shown that some antifriction devices perform better than others. In most instances the performance of the plate type of binding compares favorable with that of toe-heel bindings using antifriction devices. For the plate type of binding the dirt particularly had a detrimental effect. It should also be pointed out that these tests were run with one particular binding. These results would not necessarily be the same if the tests were conducted with another binding system. For instance, the limited motion of some of the antifriction devices (Lotork, Skidder) may impede their performance when used with bindings requiring a greater travel distance before release. The performance with other boot soles may be different from that with the particular boot sole used for these tests. Performance might be improved with a harder, smoother boot sole. Similarly, the effectiveness of the antifriction device may be reduced by the use of boot soles with a coarse pattern or relatively soft treads. In this test series a relatively small number of antifriction devices were evaluated. One should not presume that all devices will perform with equal effectiveness. Another factor, equally important, is the correction for the height of antifriction devices. Antifriction devices raise the boot sole from the ski surface, and if this change in height is not accounted for, the boot sole may effectively interfere with the operation of the toe or the heel unit. In summary, it can be stated that when properly applied and selected, antifriction devices make a significant contribution to skiing safety."} {"id": "PMID:1256781", "title": "Theoretical estimation of binding release values.", "content": "In summary, it can be stated that the optimal binding setting for either the inadvertent release criterion or for the fracture criterion is a function of the binding characteristics. This study suggests that such binding characteristics should be a factor incorporated in recommended binding setting tables for the recreational skier. Bindings with large motions (large energy absorption capabilities) are most likely to meet both the fracture and inadvertent release criteria. Bindings with large motions are more likely to cause fracture if friction exists. This study emphasizes the necessity for reducing binding friction to an absolute minimum. Frictional resistance seriously compromises the performance of contemporary bindings.", "contents": "Theoretical estimation of binding release values. In summary, it can be stated that the optimal binding setting for either the inadvertent release criterion or for the fracture criterion is a function of the binding characteristics. This study suggests that such binding characteristics should be a factor incorporated in recommended binding setting tables for the recreational skier. Bindings with large motions (large energy absorption capabilities) are most likely to meet both the fracture and inadvertent release criteria. Bindings with large motions are more likely to cause fracture if friction exists. This study emphasizes the necessity for reducing binding friction to an absolute minimum. Frictional resistance seriously compromises the performance of contemporary bindings."} {"id": "PMID:1256782", "title": "Modeling of the human leg in ski injuries.", "content": "This study establishes that the human lower extremity-ski system has a fundamental frequency of approximately 1 Hz. The fundamental mode dominates the system response when loading times are short compared to the first natural frequency. Consequently, the use of a single degree of freedom approximation and the use of impulse criteria can provide important insights into the problem of skiing injuries. Specifically, the sport of snow skiing develops forces with frequency content in the static, transition, and impulse regions of the leg-ski response spectrum. Therefore, ski release bindings must be designed to safely and effectively couple the leg to the ski throughout this loading environment. An important means of evaluating possible binding designs is by simulating their characteristics in a computer model. The model will apply realistic loading histories to the ski or binding, will evaluate the strain in the bones and ligaments of the lower extremity, and will determine the release point of the binding. The program presented in this discussion is one stage in the development of this total system capability.", "contents": "Modeling of the human leg in ski injuries. This study establishes that the human lower extremity-ski system has a fundamental frequency of approximately 1 Hz. The fundamental mode dominates the system response when loading times are short compared to the first natural frequency. Consequently, the use of a single degree of freedom approximation and the use of impulse criteria can provide important insights into the problem of skiing injuries. Specifically, the sport of snow skiing develops forces with frequency content in the static, transition, and impulse regions of the leg-ski response spectrum. Therefore, ski release bindings must be designed to safely and effectively couple the leg to the ski throughout this loading environment. An important means of evaluating possible binding designs is by simulating their characteristics in a computer model. The model will apply realistic loading histories to the ski or binding, will evaluate the strain in the bones and ligaments of the lower extremity, and will determine the release point of the binding. The program presented in this discussion is one stage in the development of this total system capability."} {"id": "PMID:1256783", "title": "The etiology of ski injuries: an eight year study of the skier and his equipment.", "content": "Detailed ski injury statistics have been maintained at Waterville Valley, New Hampshire, since the opening of the area as a major ski resort in 1966. These statistics were examined to uncover some of the major contributory factors involved in ski accidents. The characteristics that set this study aside from other such reports are the inclusion of both an adequately sized normal control population and the longitudinal collection of comparable data from a relatively stable skiing population over an eight year period, to reveal trends in the number and type of accidents.", "contents": "The etiology of ski injuries: an eight year study of the skier and his equipment. Detailed ski injury statistics have been maintained at Waterville Valley, New Hampshire, since the opening of the area as a major ski resort in 1966. These statistics were examined to uncover some of the major contributory factors involved in ski accidents. The characteristics that set this study aside from other such reports are the inclusion of both an adequately sized normal control population and the longitudinal collection of comparable data from a relatively stable skiing population over an eight year period, to reveal trends in the number and type of accidents."} {"id": "PMID:1256786", "title": "Effect of flow material ski boots on foot circulation.", "content": "The effect of modern \"flow material\" ski boots on foot circulation was studied. Pressure inside a flow material ski boot was found to be markedly higher than in a conventional ski boot. In some places the pressure exceeded the diastolic pressure in the foot. 113mIndium chloride, which when injected intravenously is bound to transferrin was used for blood pool scanning. In healthy young volunteers the uptake of radioactivity in the two feet--one with and one without a ski boot--was compared. The activity level of the foot with the ski boot was significantly lower than in the other foot. After corrections were made for absorption by the boot, a significant difference remained. Plethysmographic studies were performed with a mercury strain gauge using a ski boot in which a hole was cut over the big toe. No difference was demonstrated between the blood pressure at the leg just above the boot top and at the big toe. The arterial pulse wave at the big toe was altered; i.e., there was an absence of a dichrotic wave. Intramuscular perfusion was studied with 133xenon. The disappearance curve in a foot with a boot was more shallow than that in a bare foot. Unbuckling resulted in an immediate fall in radioactivity, the disappearance curve then becoming identical to that of the bare foot. The results indicate that when flow material ski boots are to be used by skiers who are not in the habit of unbuckling for short intervals, buckle tension should not be too high.", "contents": "Effect of flow material ski boots on foot circulation. The effect of modern \"flow material\" ski boots on foot circulation was studied. Pressure inside a flow material ski boot was found to be markedly higher than in a conventional ski boot. In some places the pressure exceeded the diastolic pressure in the foot. 113mIndium chloride, which when injected intravenously is bound to transferrin was used for blood pool scanning. In healthy young volunteers the uptake of radioactivity in the two feet--one with and one without a ski boot--was compared. The activity level of the foot with the ski boot was significantly lower than in the other foot. After corrections were made for absorption by the boot, a significant difference remained. Plethysmographic studies were performed with a mercury strain gauge using a ski boot in which a hole was cut over the big toe. No difference was demonstrated between the blood pressure at the leg just above the boot top and at the big toe. The arterial pulse wave at the big toe was altered; i.e., there was an absence of a dichrotic wave. Intramuscular perfusion was studied with 133xenon. The disappearance curve in a foot with a boot was more shallow than that in a bare foot. Unbuckling resulted in an immediate fall in radioactivity, the disappearance curve then becoming identical to that of the bare foot. The results indicate that when flow material ski boots are to be used by skiers who are not in the habit of unbuckling for short intervals, buckle tension should not be too high."} {"id": "PMID:1256787", "title": "Reconstruction of the anterior cruciate ligament.", "content": "A report is given of a personal series of 72 cases of injury of the anterior cruciate ligament, reconstructed by use of modifications of the Jones procedure. After one year, stability of the knee without a drawer sign was obtained in 80 per cent of the cases.", "contents": "Reconstruction of the anterior cruciate ligament. A report is given of a personal series of 72 cases of injury of the anterior cruciate ligament, reconstructed by use of modifications of the Jones procedure. After one year, stability of the knee without a drawer sign was obtained in 80 per cent of the cases."} {"id": "PMID:1256788", "title": "Boot top fractures.", "content": "Low transverse fractures of the tibiofibular complex due to ski injuries were formerly virtually unknown but are now met in ever increasing numbers. A series of 126 such fractures occurring in patients 13 years or older was analyzed. The sex and age distributions of these patients were found to differ significantly from those in skiers with other tibial shaft fractures. Among boot top fractures cases, boys younger than 20 years predominated much more than among patients with other fractures of the tibial shaft. In the boot top fracture there is characteristically a backward angulation, which may be combined with a forward displacement of the distal fragment. A simple technique for reduction of this typical deformity is described. According to this technique the surgeon should take a steady grip on the foot held in extreme plantar flexion. By applying strong traction, disimpaction is achieved after which the distal fragment is forced back into position and the fracture is immobilized with the foot in full equinus. This technique was successfully applied in the majority of our cases (112 of 126). Patients with boot top fractures were hospitalized for shorter periods than were skiers with other tibial fractures, and they were able to resume their normal activities much sooner. This held true even when allowance was made for differences in age. During the last few years a new type of boot top fracture has been observed. In this type there is a forward instead of a backward angulation. Its occurrence is most probably related to the new \"scoot foot\" or \"sitting back\" technique in downhill skiing. The appearance of this new type of boot top fracture implies that successful prevention can be achieved only with safety bindings that release not only at rotation but also when the skier falls backward.", "contents": "Boot top fractures. Low transverse fractures of the tibiofibular complex due to ski injuries were formerly virtually unknown but are now met in ever increasing numbers. A series of 126 such fractures occurring in patients 13 years or older was analyzed. The sex and age distributions of these patients were found to differ significantly from those in skiers with other tibial shaft fractures. Among boot top fractures cases, boys younger than 20 years predominated much more than among patients with other fractures of the tibial shaft. In the boot top fracture there is characteristically a backward angulation, which may be combined with a forward displacement of the distal fragment. A simple technique for reduction of this typical deformity is described. According to this technique the surgeon should take a steady grip on the foot held in extreme plantar flexion. By applying strong traction, disimpaction is achieved after which the distal fragment is forced back into position and the fracture is immobilized with the foot in full equinus. This technique was successfully applied in the majority of our cases (112 of 126). Patients with boot top fractures were hospitalized for shorter periods than were skiers with other tibial fractures, and they were able to resume their normal activities much sooner. This held true even when allowance was made for differences in age. During the last few years a new type of boot top fracture has been observed. In this type there is a forward instead of a backward angulation. Its occurrence is most probably related to the new \"scoot foot\" or \"sitting back\" technique in downhill skiing. The appearance of this new type of boot top fracture implies that successful prevention can be achieved only with safety bindings that release not only at rotation but also when the skier falls backward."} {"id": "PMID:1256789", "title": "Bilateral fractures of the lower leg due to skiing accidents.", "content": "The results of treatment in 13 bilateral lower leg fractures due to skiing accidents are presented. All patients were treated by internal fixation according to the principles of the Swiss Association for the Study of Internal Fixation. The patients on the average were mobilized after nine days, discharged after 24 days, started to use walking braces after 17 days, and undertook partial weight bearing 10 weeks and full weight bearing 14 weeks after the accident.", "contents": "Bilateral fractures of the lower leg due to skiing accidents. The results of treatment in 13 bilateral lower leg fractures due to skiing accidents are presented. All patients were treated by internal fixation according to the principles of the Swiss Association for the Study of Internal Fixation. The patients on the average were mobilized after nine days, discharged after 24 days, started to use walking braces after 17 days, and undertook partial weight bearing 10 weeks and full weight bearing 14 weeks after the accident."} {"id": "PMID:1256790", "title": "Comparison of stainless steel and composite plates in the healing of diaphyseal osteotomies of the dog radius: report on a short term study.", "content": "The rigid fixation of fractures is generally accepted as the best method to achieve union when open treatment of a fracture is undertaken. This has led to the development of plates that have a greater overall dimension and stiffness compared to earlier plate models, as exemplified by the Lane or Eggers type of plate. In our experience the more rigid plate generally leads to satisfactory union, but also carries with it the risk of refracture, either through a screw hole or across the original fracture after plate removal. Experiments by Uhtoff and Dubuc on experimental animals showed that plate induced osteopenia existed when a rigid plate was applied to an intact or osteomized canine femur. These results provide a possible explanation for the occurrence of late fracture. The study to be described is based on the hypothesis that a rigid plate applied to bone induced localized immobilization osteopenia, which ultimately weakens the bone and leads to the development of late fracture. The study was designed to compare a plate made of stainless steel, which exhibited mechanical stiffness comparable to that of devices presently in use, with a plate made of a composite material, which exhibited decreased stiffness by nearly one order of magnitude. It had been demonstrated by engineering analysis that the less stiff plate would allow the bone to experience normal loading, and it was thought that this loading would modulate the rate and pattern of bone remodeling, thereby resulting in bone of greater strength and size as compared to a more rigidly plated bone.", "contents": "Comparison of stainless steel and composite plates in the healing of diaphyseal osteotomies of the dog radius: report on a short term study. The rigid fixation of fractures is generally accepted as the best method to achieve union when open treatment of a fracture is undertaken. This has led to the development of plates that have a greater overall dimension and stiffness compared to earlier plate models, as exemplified by the Lane or Eggers type of plate. In our experience the more rigid plate generally leads to satisfactory union, but also carries with it the risk of refracture, either through a screw hole or across the original fracture after plate removal. Experiments by Uhtoff and Dubuc on experimental animals showed that plate induced osteopenia existed when a rigid plate was applied to an intact or osteomized canine femur. These results provide a possible explanation for the occurrence of late fracture. The study to be described is based on the hypothesis that a rigid plate applied to bone induced localized immobilization osteopenia, which ultimately weakens the bone and leads to the development of late fracture. The study was designed to compare a plate made of stainless steel, which exhibited mechanical stiffness comparable to that of devices presently in use, with a plate made of a composite material, which exhibited decreased stiffness by nearly one order of magnitude. It had been demonstrated by engineering analysis that the less stiff plate would allow the bone to experience normal loading, and it was thought that this loading would modulate the rate and pattern of bone remodeling, thereby resulting in bone of greater strength and size as compared to a more rigidly plated bone."} {"id": "PMID:1256791", "title": "The skiing sequelae of tibial torsion.", "content": "The purpose of this communication is to support the following hypotheses: 1. That variations in tibial torsion are functionally important in parallel skiing. 2. That external tibial torsion in particular is a \"deformity\" that can interfere markedly with parallel skiing. 3. That even normal individuals have greater external torsion of the right tibia than the left, and that this normal difference may correlate with the preference of many skiers for traversing and maneuvering primarily in one direction. 4. That a relatively small difference in the anatomic alignment of the lower extremities may entail substantial alterations in balance and in distribution of forces in the skier and that these differences should be searched out by centers preparing to equip skiers with bindings and skiis in an attempt to further refine the skier-ski linkage. These hypotheses derive from a blend of the personal experience of the principal author and a detailed search of the English and French literature of the past century relating to rotational alignment, motion, and control of the lower extremity in general, and to tibial torsion in particular.", "contents": "The skiing sequelae of tibial torsion. The purpose of this communication is to support the following hypotheses: 1. That variations in tibial torsion are functionally important in parallel skiing. 2. That external tibial torsion in particular is a \"deformity\" that can interfere markedly with parallel skiing. 3. That even normal individuals have greater external torsion of the right tibia than the left, and that this normal difference may correlate with the preference of many skiers for traversing and maneuvering primarily in one direction. 4. That a relatively small difference in the anatomic alignment of the lower extremities may entail substantial alterations in balance and in distribution of forces in the skier and that these differences should be searched out by centers preparing to equip skiers with bindings and skiis in an attempt to further refine the skier-ski linkage. These hypotheses derive from a blend of the personal experience of the principal author and a detailed search of the English and French literature of the past century relating to rotational alignment, motion, and control of the lower extremity in general, and to tibial torsion in particular."} {"id": "PMID:1256792", "title": "First aid on the ski slopes.", "content": "In administering first aid on ski slopes, the principles followed are basic ones: arrest of hemorrhage, adequate immobilization of fractures, prevention of shock, and relief of pain. Respiratory and circulatory complications must of course be given priority, but in my experience such situations have not arisen.", "contents": "First aid on the ski slopes. In administering first aid on ski slopes, the principles followed are basic ones: arrest of hemorrhage, adequate immobilization of fractures, prevention of shock, and relief of pain. Respiratory and circulatory complications must of course be given priority, but in my experience such situations have not arisen."} {"id": "PMID:1256793", "title": "Ski injuries in Sweden: a one year survey.", "content": "In a study of ski injuries in Sweden in 1973-1974, information regarding 1199 ski injuries was obtained. Downhill skiing was responsible for 75 per cent of the injuries. Cross country skiing proved to be a safe sport. Poor adjustment of release bindings, skiing at too high a speed, and deficiencies in the slopes were the most common causes of injury. The investigation led to an information program that seems to have reduced the injury rate by 25 to 30 per cent.", "contents": "Ski injuries in Sweden: a one year survey. In a study of ski injuries in Sweden in 1973-1974, information regarding 1199 ski injuries was obtained. Downhill skiing was responsible for 75 per cent of the injuries. Cross country skiing proved to be a safe sport. Poor adjustment of release bindings, skiing at too high a speed, and deficiencies in the slopes were the most common causes of injury. The investigation led to an information program that seems to have reduced the injury rate by 25 to 30 per cent."} {"id": "PMID:1256795", "title": "The Australian skier: his environment, injuries, and some aspects of casualty transport.", "content": "Skiing in Australia is not a new phenomenon. Since the early 1890s, when miners in the snowfield regions discovered snowshoeing using wooden palings, the craze has steadily grown in Australia, as in other countries. The Australian winter occurs six months out of phase with the northern winter, but we also have other unique problems in regard to skiing conditions, and therefore possibly ski trauma. This presentation discusses first our local skiing conditions and then presents some statistics from one of our major resorts. Two aids used by our emergency services may also be of interest.", "contents": "The Australian skier: his environment, injuries, and some aspects of casualty transport. Skiing in Australia is not a new phenomenon. Since the early 1890s, when miners in the snowfield regions discovered snowshoeing using wooden palings, the craze has steadily grown in Australia, as in other countries. The Australian winter occurs six months out of phase with the northern winter, but we also have other unique problems in regard to skiing conditions, and therefore possibly ski trauma. This presentation discusses first our local skiing conditions and then presents some statistics from one of our major resorts. Two aids used by our emergency services may also be of interest."} {"id": "PMID:1256796", "title": "Factors contributing to the production of skiing injuries.", "content": "The cause of the accident was analyzed in 981 individuals sustaining skiing injuries. Exhaustion, poor physical condition, and poor skiing technique were the most frequent causes, but poorly prepared slopes also were an important factor.", "contents": "Factors contributing to the production of skiing injuries. The cause of the accident was analyzed in 981 individuals sustaining skiing injuries. Exhaustion, poor physical condition, and poor skiing technique were the most frequent causes, but poorly prepared slopes also were an important factor."} {"id": "PMID:1256797", "title": "The risk of injury in experienced Alpine skiers.", "content": "In 981 skiing accidents the type of injury resulting was studied in relation to the skiing activity (long distance, cross country, and downhill) and to the type of boots used. From the patterns of injuries it appears that in downhill skiing not only the velocity but also the particular type of equipment used is responsible for the increased incidence and for the characteristic type of injuries. The alpine ski boot used in downhill skiing, however, seems to protect the ankle joint and the foot from injuries that are more common in cross-country and long distance skiing.", "contents": "The risk of injury in experienced Alpine skiers. In 981 skiing accidents the type of injury resulting was studied in relation to the skiing activity (long distance, cross country, and downhill) and to the type of boots used. From the patterns of injuries it appears that in downhill skiing not only the velocity but also the particular type of equipment used is responsible for the increased incidence and for the characteristic type of injuries. The alpine ski boot used in downhill skiing, however, seems to protect the ankle joint and the foot from injuries that are more common in cross-country and long distance skiing."} {"id": "PMID:1256798", "title": "Injuries in long distance, cross country, and downhill skiing.", "content": "In 981 skiing accidents the type of injury resulting was studied in relation to the skiing activity (long distance, cross country, and downhill) and to the type of boots used. From the patterns of injuries it appears that in downhill skiing not only the velocity but also the particular type of equipment used is responsible for the increased incidence and for the characteristic types of injuries. The alpine ski boot used in downhill skiing, however, seems to protect the ankle joint and the foot from injuries that are more common in cross country and long distance skiing.", "contents": "Injuries in long distance, cross country, and downhill skiing. In 981 skiing accidents the type of injury resulting was studied in relation to the skiing activity (long distance, cross country, and downhill) and to the type of boots used. From the patterns of injuries it appears that in downhill skiing not only the velocity but also the particular type of equipment used is responsible for the increased incidence and for the characteristic types of injuries. The alpine ski boot used in downhill skiing, however, seems to protect the ankle joint and the foot from injuries that are more common in cross country and long distance skiing."} {"id": "PMID:1256800", "title": "Experimental biomechanics of the human leg. A basis for interpreting typical skiing injury mechanisms.", "content": "In 1965 the continually increasing number of injured skiers inspired us to consider a special program for the prevention of injuries in alpine skiing (Fig. 1A). All the common measures used to prevent injuries resulting from a dangerous fall by the skier were apparently insufficient. Release bindings provided only limited protection for the leg, for in 63 per cent of the cases of injury the binding had not released. Moreover, no definite information was available concerning the adjustment of release bindings for maximal safety. Finally, the mechanical and dynamic characteristics of safe release bindings were not known. In alpine skiing the tibia is the most frequent site of severe injury. In such a fall the tibia is the weakest link in the lower extremity. Thus, biomechanical research was started in 1965 to study the injury threshold of this body segment. Initially we determined the relationships of bone dimensions, sex, and age to the biomechanical characteristics of the tibia.", "contents": "Experimental biomechanics of the human leg. A basis for interpreting typical skiing injury mechanisms. In 1965 the continually increasing number of injured skiers inspired us to consider a special program for the prevention of injuries in alpine skiing (Fig. 1A). All the common measures used to prevent injuries resulting from a dangerous fall by the skier were apparently insufficient. Release bindings provided only limited protection for the leg, for in 63 per cent of the cases of injury the binding had not released. Moreover, no definite information was available concerning the adjustment of release bindings for maximal safety. Finally, the mechanical and dynamic characteristics of safe release bindings were not known. In alpine skiing the tibia is the most frequent site of severe injury. In such a fall the tibia is the weakest link in the lower extremity. Thus, biomechanical research was started in 1965 to study the injury threshold of this body segment. Initially we determined the relationships of bone dimensions, sex, and age to the biomechanical characteristics of the tibia."} {"id": "PMID:1256801", "title": "Fundamental considerations in ski binding analysis.", "content": "1. The static adjustment of a ski binding by hand or by available machines is only an adjustment and is neither a static nor a dynamic evaluation of the binding design. Bindings of different design with identical static adjustments will perform differently in environments in which the forces are static or dynamic. 2. The concept of binding release force is a useful measure of binding adjustment, but it is inappropriate as a criterion for binding evaluation. First, it does not direct attention toward the injury causing mechanism, strain, or displacement in the leg. Second, it is only part of the evaluation in dynamic problems. 3. The binding release decision in present bindings is displacement controlled. The relative displacement of the boot and ski is the system variable. For any specified relative displacement the binding force can be any of an infinite number of possibilities determined by the loading path. 4. The response of the leg-ski system to external impulses applied to the ski is independent of the boot-ski relative motion as long as the boot recenters quickly in the binding. Response is dependent upon the external impulse plus system inertia, damping and stiffness. 5. When tested under half sinusoidal forces applied to a test ski, all bindings will demonstrate static and impulse loading regions. In the static region the force drives the binding to a relative release displacement. In the impulse region the initial velocity of the ski drives the binding to a release displacement. 6. The transition between the static and impulse loading regions is determined by the binding's capacity to store and dissipate energy along the principal loading path. Increased energy capacity necessitates larger external impulses to produce release. 7. In all bindings examined to date, the transmitted leg displacement or strain at release under static loading exceeds leg strain under dynamic or impact loading. Because static loading is responsible for many injuries, a skier should be able to release his bindings in every mode by simply pulling or twisting his foot outward. If that cannot be done without injury, the skier has identified for himself one type of fall that will result in injury. 8. And lastly, a little advice from Ben Franklin--\"Carelessness does more harm than a want of knowledge.\"", "contents": "Fundamental considerations in ski binding analysis. 1. The static adjustment of a ski binding by hand or by available machines is only an adjustment and is neither a static nor a dynamic evaluation of the binding design. Bindings of different design with identical static adjustments will perform differently in environments in which the forces are static or dynamic. 2. The concept of binding release force is a useful measure of binding adjustment, but it is inappropriate as a criterion for binding evaluation. First, it does not direct attention toward the injury causing mechanism, strain, or displacement in the leg. Second, it is only part of the evaluation in dynamic problems. 3. The binding release decision in present bindings is displacement controlled. The relative displacement of the boot and ski is the system variable. For any specified relative displacement the binding force can be any of an infinite number of possibilities determined by the loading path. 4. The response of the leg-ski system to external impulses applied to the ski is independent of the boot-ski relative motion as long as the boot recenters quickly in the binding. Response is dependent upon the external impulse plus system inertia, damping and stiffness. 5. When tested under half sinusoidal forces applied to a test ski, all bindings will demonstrate static and impulse loading regions. In the static region the force drives the binding to a relative release displacement. In the impulse region the initial velocity of the ski drives the binding to a release displacement. 6. The transition between the static and impulse loading regions is determined by the binding's capacity to store and dissipate energy along the principal loading path. Increased energy capacity necessitates larger external impulses to produce release. 7. In all bindings examined to date, the transmitted leg displacement or strain at release under static loading exceeds leg strain under dynamic or impact loading. Because static loading is responsible for many injuries, a skier should be able to release his bindings in every mode by simply pulling or twisting his foot outward. If that cannot be done without injury, the skier has identified for himself one type of fall that will result in injury. 8. And lastly, a little advice from Ben Franklin--\"Carelessness does more harm than a want of knowledge.\""} {"id": "PMID:1256906", "title": "Effects of a series of infections of Ostertagia circumcincta on gastric secretion of sheep.", "content": "Sheep which had been either previously infected with 3. circumcincta or maintained worm-free, were surgically prepared with separated fundic pouches and abomasal cannulae and subsequently infected with 20,000 O. circumcincta larvae three times weekly. A reduction in food intake and increases in total acid output from the pouches and plasma pepsinogen levels were evident in both groups of sheep 4 days after repeated infections commenced; effects which increased in severity after 12 or more days. Except for a transient period of slight failure, previously infected sheep retained the capacity to acidify their abomasal contents whereas previously worm-free sheep lost this capacity. These changes were reversed between 2 and 7 days after treatment with thiabendazole (88 mg.kg-1). Secretory capacity of the fundic pouches was tested with histamine (40 mug.kg-1), the histamine antagonist (burimamide 8 mg.kg-1) and atropine (100 mug.kg-1). Ostertagiasis reduced or abolished the stimulatory effects of histamine. An increase in secretion volume and acid output was obtained after food was freshly provided, even though as little as 25 gm was consumed. Atropine and burimamide both caused a profound decrease in pouch secretion and acid output. These data are consistent with the hypothesis previously stated that in ostertagiasis the hypersecretion from fundic pouches is due to increased levels of circulating gastrin.", "contents": "Effects of a series of infections of Ostertagia circumcincta on gastric secretion of sheep. Sheep which had been either previously infected with 3. circumcincta or maintained worm-free, were surgically prepared with separated fundic pouches and abomasal cannulae and subsequently infected with 20,000 O. circumcincta larvae three times weekly. A reduction in food intake and increases in total acid output from the pouches and plasma pepsinogen levels were evident in both groups of sheep 4 days after repeated infections commenced; effects which increased in severity after 12 or more days. Except for a transient period of slight failure, previously infected sheep retained the capacity to acidify their abomasal contents whereas previously worm-free sheep lost this capacity. These changes were reversed between 2 and 7 days after treatment with thiabendazole (88 mg.kg-1). Secretory capacity of the fundic pouches was tested with histamine (40 mug.kg-1), the histamine antagonist (burimamide 8 mg.kg-1) and atropine (100 mug.kg-1). Ostertagiasis reduced or abolished the stimulatory effects of histamine. An increase in secretion volume and acid output was obtained after food was freshly provided, even though as little as 25 gm was consumed. Atropine and burimamide both caused a profound decrease in pouch secretion and acid output. These data are consistent with the hypothesis previously stated that in ostertagiasis the hypersecretion from fundic pouches is due to increased levels of circulating gastrin."} {"id": "PMID:1256907", "title": "The occurrence of Eimeria marsica in the domestic sheep in England and Wales.", "content": "Eimeria marsica Restani 1971 is re-described from oocysts recovered in pure culture from experimentally infected coccidia-free lambs. The ellipsoidal oocysts, which measure 19-1 x 13-1 mum, possess an inconspicuous micropylar cap. The prepatent period varies from 14-16 days. E. marsica is recorded for the first time from sheep in England.", "contents": "The occurrence of Eimeria marsica in the domestic sheep in England and Wales. Eimeria marsica Restani 1971 is re-described from oocysts recovered in pure culture from experimentally infected coccidia-free lambs. The ellipsoidal oocysts, which measure 19-1 x 13-1 mum, possess an inconspicuous micropylar cap. The prepatent period varies from 14-16 days. E. marsica is recorded for the first time from sheep in England."} {"id": "PMID:1256908", "title": "The immunity arising from continuous low-level infection with Eimeria maxima and Eimeria acervulina.", "content": "Chicks were given daily inoculations of 1 or 5 oocysts of Eimeria maxima or 5 or 20 oocysts of E. acervulina. The inoculations ceased after 20 days with E. maxima or 25 days with E. acervulina when oocyst production had stopped. The responses to subsequent heavy challenges showed that with both species the immunity arising from the serial inoculations was stronger and/or more enduring than that produced by single inoculations of comparable numbers of oocysts.", "contents": "The immunity arising from continuous low-level infection with Eimeria maxima and Eimeria acervulina. Chicks were given daily inoculations of 1 or 5 oocysts of Eimeria maxima or 5 or 20 oocysts of E. acervulina. The inoculations ceased after 20 days with E. maxima or 25 days with E. acervulina when oocyst production had stopped. The responses to subsequent heavy challenges showed that with both species the immunity arising from the serial inoculations was stronger and/or more enduring than that produced by single inoculations of comparable numbers of oocysts."} {"id": "PMID:1256909", "title": "Immune expulsion of Trichuris muris from resistant mice: suppression by irradiation and restoration by transfer of lymphoid cells.", "content": "Lethal irradiation (850 rads) of mice made resistant to Trichuris muris markedly depressed their ability to expel a challenge infection. Expulsion was restored within 7-10 days when MLNC from uninfected mice were transferred on the day of infection, but no significant restoration was evident after transfer of immune serum. Transfer of BM alone had no restorative effect within 10 days and no synergism was seen when both BM and MLNC were transferred. MLNC from uninfected donors did not restore challenge expulsion when transfer was delayed until day 7 and the mice were killed 3 days later, although MLNC from resistant donors were effective within this time. When irradiated mice were given BM and the challenge infection allowed to continue for 15 days expulsion was restored, as it was when challenge was delayed for 7 days after BM transfer in thymectomized mice. The results confirm that expulsion of T. muris involves both antibody-mediated and lymphoid cell-mediated phases and offer no evidence for the involvement of other cell types.", "contents": "Immune expulsion of Trichuris muris from resistant mice: suppression by irradiation and restoration by transfer of lymphoid cells. Lethal irradiation (850 rads) of mice made resistant to Trichuris muris markedly depressed their ability to expel a challenge infection. Expulsion was restored within 7-10 days when MLNC from uninfected mice were transferred on the day of infection, but no significant restoration was evident after transfer of immune serum. Transfer of BM alone had no restorative effect within 10 days and no synergism was seen when both BM and MLNC were transferred. MLNC from uninfected donors did not restore challenge expulsion when transfer was delayed until day 7 and the mice were killed 3 days later, although MLNC from resistant donors were effective within this time. When irradiated mice were given BM and the challenge infection allowed to continue for 15 days expulsion was restored, as it was when challenge was delayed for 7 days after BM transfer in thymectomized mice. The results confirm that expulsion of T. muris involves both antibody-mediated and lymphoid cell-mediated phases and offer no evidence for the involvement of other cell types."} {"id": "PMID:1256910", "title": "The feeding behaviour of larvae, nymphs and adults of Rhipicephalus appendiculatus.", "content": "The pre-feeding and feeding periods of larvae, nymphs and adults of Rhipicephalus appendiculatus on rabbits (Oryctolagus cuniculus) were investigated. Larvae and nymphs required at least 8-9 days after hatching and moulting respectively before they could attach and start feeding, while adults required at least 6-9 days. But longer periods of starvation improved the proportion of ticks that successfully fed. After attachment, there was always an initial period of slow feeding, which was followed by a phase of very rapid feeding before the engorged ticks detached from the host. Larvae detached 4-5 days after attachment, nymphs detached after 5-6 days and adults detached 7-9 days after attachment.", "contents": "The feeding behaviour of larvae, nymphs and adults of Rhipicephalus appendiculatus. The pre-feeding and feeding periods of larvae, nymphs and adults of Rhipicephalus appendiculatus on rabbits (Oryctolagus cuniculus) were investigated. Larvae and nymphs required at least 8-9 days after hatching and moulting respectively before they could attach and start feeding, while adults required at least 6-9 days. But longer periods of starvation improved the proportion of ticks that successfully fed. After attachment, there was always an initial period of slow feeding, which was followed by a phase of very rapid feeding before the engorged ticks detached from the host. Larvae detached 4-5 days after attachment, nymphs detached after 5-6 days and adults detached 7-9 days after attachment."} {"id": "PMID:1256911", "title": "Observations on crystals found in the intestine of Nematodirus battus during the development of immunity to this nematode in lambs.", "content": "Lambs which were given 60000 infective larvae of Nematodirus battus progressively threw off adult nematodes from day 20 onwards. Large, hexagonal crystals appeared in the intestine of the adult nematode at about this time and caused blockage of the intestinal-rectal or -cloacal junction. Lambs which were given 1000-2000 infective larvae did not throw off the infection, and adult nematodes from lambs which had been infected for up to 74 days did not contain these crystals. Chemical, histochemical and x-ray microanalysis tests on the crystals indicated that they are lipoprotein in composition. The crystals arise within the lumen of the nematode and appear to be associated with the development of immunity to this nematode in lambs.", "contents": "Observations on crystals found in the intestine of Nematodirus battus during the development of immunity to this nematode in lambs. Lambs which were given 60000 infective larvae of Nematodirus battus progressively threw off adult nematodes from day 20 onwards. Large, hexagonal crystals appeared in the intestine of the adult nematode at about this time and caused blockage of the intestinal-rectal or -cloacal junction. Lambs which were given 1000-2000 infective larvae did not throw off the infection, and adult nematodes from lambs which had been infected for up to 74 days did not contain these crystals. Chemical, histochemical and x-ray microanalysis tests on the crystals indicated that they are lipoprotein in composition. The crystals arise within the lumen of the nematode and appear to be associated with the development of immunity to this nematode in lambs."} {"id": "PMID:1256912", "title": "Some observations on egg production and autoreinfection of Reighardia sternae (Diesing, 1864), a pentastomid parasite of the herring gull.", "content": "Egg production by Reighardia sternae, implanted at various stages of maturity into the interclavicular air sacs of captive gulls, is described. Females produce only 2900 eggs per lifetime over a short patent period of 1-3 days. The problem of a direct life-cycle in relation to this unusually low fecundity is discussed, and speculation is advanced concerning a possible parasitic behavioural trait which could facilitate direct transmission. The hazards of the latter are also offset by auto-reinfection.", "contents": "Some observations on egg production and autoreinfection of Reighardia sternae (Diesing, 1864), a pentastomid parasite of the herring gull. Egg production by Reighardia sternae, implanted at various stages of maturity into the interclavicular air sacs of captive gulls, is described. Females produce only 2900 eggs per lifetime over a short patent period of 1-3 days. The problem of a direct life-cycle in relation to this unusually low fecundity is discussed, and speculation is advanced concerning a possible parasitic behavioural trait which could facilitate direct transmission. The hazards of the latter are also offset by auto-reinfection."} {"id": "PMID:1256913", "title": "Immunity to Hymenolepis diminuta: unresponsiveness of the athymic nude mouse to infection.", "content": "Male and female congenitally athymic nude (nu/nu) mice infected with a single cysticercoid of Hymenolepis diminuta at 6 weeks of age retain the infection for at least 33 days. In the males of their phenotypically normal litter-mates, however, a single cysticercoid infection establishes and grows but is expelled between days 11 and 17. The unresponsiveness of the nude mouse to single H. diminuta infection is evidence that the immune rejection from normal mice is thymus-dependent.", "contents": "Immunity to Hymenolepis diminuta: unresponsiveness of the athymic nude mouse to infection. Male and female congenitally athymic nude (nu/nu) mice infected with a single cysticercoid of Hymenolepis diminuta at 6 weeks of age retain the infection for at least 33 days. In the males of their phenotypically normal litter-mates, however, a single cysticercoid infection establishes and grows but is expelled between days 11 and 17. The unresponsiveness of the nude mouse to single H. diminuta infection is evidence that the immune rejection from normal mice is thymus-dependent."} {"id": "PMID:1256941", "title": "Anaerobic infections in children: a prospective study.", "content": "The prevalence and significance of anaerobic infections in patients at St. Louis Children's Hospital were studied prospectively for a one-year period. Blood, selected body fluids, and aspirates obtained from abscesses or areas of cellulitis were cultured using special anaerobic collection and processing techniques. Infected peritoneal fluid from patients with gastrointestinal disease yielded a large proportion of all anaerobic isolates. The types of organisms isolated were common inhabitants of the intestinal tract. Anaerobic organisms were recovered from only 0.75% of all blood cultures; anaerobic bacteremia accounted for 5.8% of all clinically significant bacteremic episodes (8.7% in the neonatal period and 4.8% in children over 1 month of age). Serious anaerobic infections occurred more frequently in the compromised host or in newborn infants than in otherwise healthy children. Since anaerobic organisms cause a small proportion of infectious diseases in a general pediatric population, the cost of refined bacteriologic techniques for the isolation and identification of these organisms is not warranted in most community hospitals. However, such a program should be available in selected tertiary care centers to aid in the management of certain high-risk patients.", "contents": "Anaerobic infections in children: a prospective study. The prevalence and significance of anaerobic infections in patients at St. Louis Children's Hospital were studied prospectively for a one-year period. Blood, selected body fluids, and aspirates obtained from abscesses or areas of cellulitis were cultured using special anaerobic collection and processing techniques. Infected peritoneal fluid from patients with gastrointestinal disease yielded a large proportion of all anaerobic isolates. The types of organisms isolated were common inhabitants of the intestinal tract. Anaerobic organisms were recovered from only 0.75% of all blood cultures; anaerobic bacteremia accounted for 5.8% of all clinically significant bacteremic episodes (8.7% in the neonatal period and 4.8% in children over 1 month of age). Serious anaerobic infections occurred more frequently in the compromised host or in newborn infants than in otherwise healthy children. Since anaerobic organisms cause a small proportion of infectious diseases in a general pediatric population, the cost of refined bacteriologic techniques for the isolation and identification of these organisms is not warranted in most community hospitals. However, such a program should be available in selected tertiary care centers to aid in the management of certain high-risk patients."} {"id": "PMID:1256942", "title": "Does watching violence on television cause apathy?", "content": "The hypothesis that exposure to televised violence serves to increase children's toleration of real-life aggression was investigated. Fifth-grade boys and girls were exposed to either a violent television excerpt or a nonviolent, exciting control program. Immediately thereafter, each child was lead to believe that he had been given responsibility for monitoring the behavior of two younger children. Subjects who had witnessed the aggressive television program were found to be significantly slower to summon appropriate adult aid when the younger children began to argue and fight than were subjects who had viewed the control film.", "contents": "Does watching violence on television cause apathy? The hypothesis that exposure to televised violence serves to increase children's toleration of real-life aggression was investigated. Fifth-grade boys and girls were exposed to either a violent television excerpt or a nonviolent, exciting control program. Immediately thereafter, each child was lead to believe that he had been given responsibility for monitoring the behavior of two younger children. Subjects who had witnessed the aggressive television program were found to be significantly slower to summon appropriate adult aid when the younger children began to argue and fight than were subjects who had viewed the control film."} {"id": "PMID:1256943", "title": "Pinna anomalies associated with congenital conductive hearing loss.", "content": "This paper compares the normal pinna with the abnormal congenitally malformed pinna. Then the abnormal pinna is related to case histories where a hearing loss was found due to a congenital malformation of the middle ear ossicles. Careful examination of the pinna, therefore, may be a simple diagnostic sign of an underlying potentially surgically correctable hearing loss. An abnormal pinna is more often associated with a middle ear anomaly than with any other congenital malformation including a urinary tract anomaly.", "contents": "Pinna anomalies associated with congenital conductive hearing loss. This paper compares the normal pinna with the abnormal congenitally malformed pinna. Then the abnormal pinna is related to case histories where a hearing loss was found due to a congenital malformation of the middle ear ossicles. Careful examination of the pinna, therefore, may be a simple diagnostic sign of an underlying potentially surgically correctable hearing loss. An abnormal pinna is more often associated with a middle ear anomaly than with any other congenital malformation including a urinary tract anomaly."} {"id": "PMID:1256944", "title": "Central hypoventilation during quiet sleep in two infants.", "content": "Expired ventilation (VE), tidal volume (VT), frequency (f), and alveolar PCO2 (PACO2) were examined in six normal infants at 41 to 52 weeks post-conceptional age and in two infants who were apneic at birth. Their response to breathing 5% carbon dioxide in air and to 100% oxygen in quiet sleep were compared to those in rapid eye movement (REM) sleep. VE in normal infants was 259 ml/kg/min in REM and 200.2 ml/kg/min in quiet sleep with the difference being due to decreased carbon dioxide production and to decreased dead space. VE increased 34.4 ml/kg/min/mm Hg of PCO2 elevation with 5% carbon dioxide breathing during REM and was not significantly different during quiet sleep. During oxygen breathing VE fell by 32.7% at 30 seconds before increasing again. In the affected infants, VE and PACO2 during REM at 1 and 4 months were normal. At 1 month, during quiet sleep, each infant became apneic and PACO2 rose 9 and 8 mm Hg/min respectively. At this time mechanical ventilation was begun. At 4 months, during quiet sleep, VE was 0.064 and 0.063 ml/kg/min at PACO2 of 66 mm Hg in each infant. The change was due entirely to a decrease in VT to 2.3 and 2.5 ml/kg. At this time 5% carbon dioxide breathing given during normal ventilation in REM produced an abrupt fall in VT to 2.0 and 2.2 ml/kg with no change in frequency. Oxygen breathing during REM at one month had no effect but at 4 months produced apnea requiring mechanical ventilation after one minute. The findings suggest that the ventilatory response to carbon dioxide is (1) important in initiation of extrauterine ventilation and (2) in sustaining ventilation particularly in quiet sleep. It is not necessary in sustaining ventilation awake or in REM sleep and it represents a balance between the stimulatory and depressant effects of carbon dioxide on the central nervous system.", "contents": "Central hypoventilation during quiet sleep in two infants. Expired ventilation (VE), tidal volume (VT), frequency (f), and alveolar PCO2 (PACO2) were examined in six normal infants at 41 to 52 weeks post-conceptional age and in two infants who were apneic at birth. Their response to breathing 5% carbon dioxide in air and to 100% oxygen in quiet sleep were compared to those in rapid eye movement (REM) sleep. VE in normal infants was 259 ml/kg/min in REM and 200.2 ml/kg/min in quiet sleep with the difference being due to decreased carbon dioxide production and to decreased dead space. VE increased 34.4 ml/kg/min/mm Hg of PCO2 elevation with 5% carbon dioxide breathing during REM and was not significantly different during quiet sleep. During oxygen breathing VE fell by 32.7% at 30 seconds before increasing again. In the affected infants, VE and PACO2 during REM at 1 and 4 months were normal. At 1 month, during quiet sleep, each infant became apneic and PACO2 rose 9 and 8 mm Hg/min respectively. At this time mechanical ventilation was begun. At 4 months, during quiet sleep, VE was 0.064 and 0.063 ml/kg/min at PACO2 of 66 mm Hg in each infant. The change was due entirely to a decrease in VT to 2.3 and 2.5 ml/kg. At this time 5% carbon dioxide breathing given during normal ventilation in REM produced an abrupt fall in VT to 2.0 and 2.2 ml/kg with no change in frequency. Oxygen breathing during REM at one month had no effect but at 4 months produced apnea requiring mechanical ventilation after one minute. The findings suggest that the ventilatory response to carbon dioxide is (1) important in initiation of extrauterine ventilation and (2) in sustaining ventilation particularly in quiet sleep. It is not necessary in sustaining ventilation awake or in REM sleep and it represents a balance between the stimulatory and depressant effects of carbon dioxide on the central nervous system."} {"id": "PMID:1256945", "title": "Incidence and clinical features of patent ductus arteriosus in low-birthweight infants: a prospective analysis of 150 consecutively born infants.", "content": "The incidence of persistent patency of the ductus arteriosus beyond the third day of life was prospectively determined in 100 preterm infants with birthweights of 2,000 gm or less and 50 infants with birthweights of 2,001 to 2,500 gm. The overall incidence was 21% and was inversely related to increasing gestational age and birthweight. The data suggest that immaturity is the major determinant of the persistent patency of the ductus arteriosus. Spontaneous delayed closure of the ductus occurred in 79% of patients that survived the immediate neonatal period. There was a high degree of association between the presence of a patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS). Eight infants with severe RDS and PDA developed heart failure and four required surgical ligation of the ductus. None of the infants with birthweights greater than 2,000 gm who had PDA developed heart failure or required surgical ligation of the ductus arteriosus.", "contents": "Incidence and clinical features of patent ductus arteriosus in low-birthweight infants: a prospective analysis of 150 consecutively born infants. The incidence of persistent patency of the ductus arteriosus beyond the third day of life was prospectively determined in 100 preterm infants with birthweights of 2,000 gm or less and 50 infants with birthweights of 2,001 to 2,500 gm. The overall incidence was 21% and was inversely related to increasing gestational age and birthweight. The data suggest that immaturity is the major determinant of the persistent patency of the ductus arteriosus. Spontaneous delayed closure of the ductus occurred in 79% of patients that survived the immediate neonatal period. There was a high degree of association between the presence of a patent ductus arteriosus (PDA) and respiratory distress syndrome (RDS). Eight infants with severe RDS and PDA developed heart failure and four required surgical ligation of the ductus. None of the infants with birthweights greater than 2,000 gm who had PDA developed heart failure or required surgical ligation of the ductus arteriosus."} {"id": "PMID:1256946", "title": "Insulin responses during catch-up growth of infants who were small for gestational age.", "content": "Growth characteristics of 15 full-term infants, selected because of weights more than 2 SD below the mean for gestational age, are described. The response to an intravenous injection of glucose was utilized to measure the insulin response of the infants at 6 months. Infants small for gestational age grow at a faster rate than appropriate-for-age infants during the first six months of life. There was a positive correlation between the growth velocity of the period and insulin release and a negative correlation between growth velocity and birth length. There was no correlation between these variables and increases in weight during the same period. Growth velocity during catch-up growth is related to the degree of preceding retardation but insulin may play a permissive role.", "contents": "Insulin responses during catch-up growth of infants who were small for gestational age. Growth characteristics of 15 full-term infants, selected because of weights more than 2 SD below the mean for gestational age, are described. The response to an intravenous injection of glucose was utilized to measure the insulin response of the infants at 6 months. Infants small for gestational age grow at a faster rate than appropriate-for-age infants during the first six months of life. There was a positive correlation between the growth velocity of the period and insulin release and a negative correlation between growth velocity and birth length. There was no correlation between these variables and increases in weight during the same period. Growth velocity during catch-up growth is related to the degree of preceding retardation but insulin may play a permissive role."} {"id": "PMID:1256947", "title": "Books for children about death.", "content": "Books about death for preschool and schoolaged children are reviewed in terms of child development, children's understanding of death, and literary quality. The article is written to help pediatricians and nurses become aware of this literature and to aid them in selectively advising concerned parents about its constructive use to help children understand death. Preventive mental health is the focus rather than use with fatally ill children.", "contents": "Books for children about death. Books about death for preschool and schoolaged children are reviewed in terms of child development, children's understanding of death, and literary quality. The article is written to help pediatricians and nurses become aware of this literature and to aid them in selectively advising concerned parents about its constructive use to help children understand death. Preventive mental health is the focus rather than use with fatally ill children."} {"id": "PMID:1256948", "title": "Dermoid cysts in children.", "content": "A retrospective study of dermoid cysts in children over the past 13 years at St. Christopher's Children's Hospital of Philadelphia, showed that 37% of the dermoids in the body occurred in the orbital and peri-orbital areas. An unusually high percentage of these occurred in the left eyebrow which appears to be the most frequent location for dermoid cysts in children. Dermoid cysts are a very common lesion encountered by ophthalmologists inasmuch as 3.3% of all ophthalmic surgical procedures in children were performed for dermoids. All 231 cases in this series were benign. The manner and time of presentation of these lesions are discussed as well as the treatment.", "contents": "Dermoid cysts in children. A retrospective study of dermoid cysts in children over the past 13 years at St. Christopher's Children's Hospital of Philadelphia, showed that 37% of the dermoids in the body occurred in the orbital and peri-orbital areas. An unusually high percentage of these occurred in the left eyebrow which appears to be the most frequent location for dermoid cysts in children. Dermoid cysts are a very common lesion encountered by ophthalmologists inasmuch as 3.3% of all ophthalmic surgical procedures in children were performed for dermoids. All 231 cases in this series were benign. The manner and time of presentation of these lesions are discussed as well as the treatment."} {"id": "PMID:1256949", "title": "Compliance with short-term antimicrobial therapy: some techniques that help.", "content": "The effect of two reminder devices on compliance with a ten-day antimicrobial prescription was investigated in a health center population. The reminders, a clock printed on the prescription label with appropriate times circled and a 5 X 7 inch bright red sticker to be posted at home, were compared to a control group. A total of 158 patients were interviewed at home on the ninth or tenth day of therapy, and compliance estimated by measuring the amount of remaining medication. For children, both reminders improved compliance about two-fold over controls. The findings suggest that (1) several simple reminder devices can be effective and (2) the nature of the patient population may be a more important influence on compliance than the relationship to a physician or the type of health care system. In addition, the study demonstrates the influence of the pharmacist on patients' medication-taking behavior.", "contents": "Compliance with short-term antimicrobial therapy: some techniques that help. The effect of two reminder devices on compliance with a ten-day antimicrobial prescription was investigated in a health center population. The reminders, a clock printed on the prescription label with appropriate times circled and a 5 X 7 inch bright red sticker to be posted at home, were compared to a control group. A total of 158 patients were interviewed at home on the ninth or tenth day of therapy, and compliance estimated by measuring the amount of remaining medication. For children, both reminders improved compliance about two-fold over controls. The findings suggest that (1) several simple reminder devices can be effective and (2) the nature of the patient population may be a more important influence on compliance than the relationship to a physician or the type of health care system. In addition, the study demonstrates the influence of the pharmacist on patients' medication-taking behavior."} {"id": "PMID:1256962", "title": "An alternative for judging confusability of visual letters.", "content": "Numerical values for shared distinctive features were derived from Gibson's (1) feature analysis of the 26 uppercase alphabet letters. Due to the lack of agreement among the empirical matrices, it is proposed that this more general table is a useful and practical approach for judging confusability of visual letters for uppercase items. Reaction time data from a Posner-type of letter-matching task support the effectiveness of the table for judging visual confusability among uppercase letters.", "contents": "An alternative for judging confusability of visual letters. Numerical values for shared distinctive features were derived from Gibson's (1) feature analysis of the 26 uppercase alphabet letters. Due to the lack of agreement among the empirical matrices, it is proposed that this more general table is a useful and practical approach for judging confusability of visual letters for uppercase items. Reaction time data from a Posner-type of letter-matching task support the effectiveness of the table for judging visual confusability among uppercase letters."} {"id": "PMID:1256963", "title": "Effects of training in design on magnitude of the M\u00fcller-Lyer illusion.", "content": "The M\u00fcller-Lyer illusion was measured for 10 design and 10 optometry students. The illusion was smaller for design students and they improved significantly with practice. The results are discussed in relation to size-constancy, according to which part of the figure corresponding to a distant object is overestimated and to the aptitude of design students to draw according to their retinal image.", "contents": "Effects of training in design on magnitude of the M\u00fcller-Lyer illusion. The M\u00fcller-Lyer illusion was measured for 10 design and 10 optometry students. The illusion was smaller for design students and they improved significantly with practice. The results are discussed in relation to size-constancy, according to which part of the figure corresponding to a distant object is overestimated and to the aptitude of design students to draw according to their retinal image."} {"id": "PMID:1256964", "title": "Relationship between WISC verbal-performance discrepancies and motor and psychomotor abilities of children with learning disabilities.", "content": "Thirty 9- to 14-yr.-old boys with learning disabilities were divided into three WISC IQ groups: High Verbal-Low Performance, Verbal equal to Performance, and High Performance-Low Verbal. All Ss were given a battery of motor and psychomotor tests. WISC IQ Verbal-Performance discrepancy was not a good predictor of motor and psychomotor learning disabilities.", "contents": "Relationship between WISC verbal-performance discrepancies and motor and psychomotor abilities of children with learning disabilities. Thirty 9- to 14-yr.-old boys with learning disabilities were divided into three WISC IQ groups: High Verbal-Low Performance, Verbal equal to Performance, and High Performance-Low Verbal. All Ss were given a battery of motor and psychomotor tests. WISC IQ Verbal-Performance discrepancy was not a good predictor of motor and psychomotor learning disabilities."} {"id": "PMID:1256965", "title": "Evaluation of two instrumental procedures for use with embedded-figures subtest of Purdue Motion-Picture Screening Test.", "content": "The purpose of this study was to determine if modification of the materials used by young Ss in responding affected their performance on a motion picture screening device. Modification of the modes of measuring responses increased the total performance of 24 kindergarten Ss; however, there appeared to be little relationship with standardized reading achievement test scores for first and second grade Ss. The approaches used appeared applicable with kindergarten Ss.", "contents": "Evaluation of two instrumental procedures for use with embedded-figures subtest of Purdue Motion-Picture Screening Test. The purpose of this study was to determine if modification of the materials used by young Ss in responding affected their performance on a motion picture screening device. Modification of the modes of measuring responses increased the total performance of 24 kindergarten Ss; however, there appeared to be little relationship with standardized reading achievement test scores for first and second grade Ss. The approaches used appeared applicable with kindergarten Ss."} {"id": "PMID:1256966", "title": "Recall of familiar objects and projected color photographys of objects by mentally retarded individuals of comparable mental age.", "content": "The effects of cue-availability on short-term and long-term recall of 40 mentally retarded children were investigated. Subjects were chosen on the basis of comparable mental age (approximately 90 mo.) and randomly assigned to either an objects (high cues) group or slides (low cues) group. 52 familiar objects served as stimuli for the objects group and projected color photographs of the objects were presented to the slides group. In the short-term recall session the subjects were shown stimuli grouped into eight trials and asked to recall the names of the stimuli in each trial ten seconds after presentation. Delayed recall was obtained 48 hr. later in a free recall session. The objects group scored significantly higher than the slides group on memory span (p less than .01), short-term recall (p less than .001), and delayed recall (p less than .025). The facilitation of recall achieved by using three-dimensional stimuli was clearly demonstrated, and the relative degree of facilitation was comparable for both short- and long-term recall.", "contents": "Recall of familiar objects and projected color photographys of objects by mentally retarded individuals of comparable mental age. The effects of cue-availability on short-term and long-term recall of 40 mentally retarded children were investigated. Subjects were chosen on the basis of comparable mental age (approximately 90 mo.) and randomly assigned to either an objects (high cues) group or slides (low cues) group. 52 familiar objects served as stimuli for the objects group and projected color photographs of the objects were presented to the slides group. In the short-term recall session the subjects were shown stimuli grouped into eight trials and asked to recall the names of the stimuli in each trial ten seconds after presentation. Delayed recall was obtained 48 hr. later in a free recall session. The objects group scored significantly higher than the slides group on memory span (p less than .01), short-term recall (p less than .001), and delayed recall (p less than .025). The facilitation of recall achieved by using three-dimensional stimuli was clearly demonstrated, and the relative degree of facilitation was comparable for both short- and long-term recall."} {"id": "PMID:1256969", "title": "The Poggendorf illusion in stereoscopic space.", "content": "The stereoscopic depth separation between the bisecting rectangle and the oblique line of a Poggendorf configuration was manipulated by varying the direction and magnitude of disparity carried by the rectangle. Based upon data of 6 subjects, the magnitude of the illusion decreased with increasing depth separation regardless of the direction of disparity. Depth separation varied directly with disparity. These findings make plain that depth adjacency can operate symmetrically in stereoscopic space.", "contents": "The Poggendorf illusion in stereoscopic space. The stereoscopic depth separation between the bisecting rectangle and the oblique line of a Poggendorf configuration was manipulated by varying the direction and magnitude of disparity carried by the rectangle. Based upon data of 6 subjects, the magnitude of the illusion decreased with increasing depth separation regardless of the direction of disparity. Depth separation varied directly with disparity. These findings make plain that depth adjacency can operate symmetrically in stereoscopic space."} {"id": "PMID:1256970", "title": "Effects of visual presentation of caloric values on food buying by normal and obese persons.", "content": "The effects of the visual presentation of the caloric values of food on the food buying behavior of 450 normal, overweight, and obese female subjects were studied, in a cafeteria setting. The caloric signs significantly decreased the total number of calories bought across all three weight groups. No differences were found among the three weight groups, either in the effect of the presentation of the caloric signs or in the total number of calories bought. The implications of these results were discussed, both in terms of present-day research on obesity as well as in terms of a large scale modification of eating behavior.", "contents": "Effects of visual presentation of caloric values on food buying by normal and obese persons. The effects of the visual presentation of the caloric values of food on the food buying behavior of 450 normal, overweight, and obese female subjects were studied, in a cafeteria setting. The caloric signs significantly decreased the total number of calories bought across all three weight groups. No differences were found among the three weight groups, either in the effect of the presentation of the caloric signs or in the total number of calories bought. The implications of these results were discussed, both in terms of present-day research on obesity as well as in terms of a large scale modification of eating behavior."} {"id": "PMID:1256971", "title": "Asynchrony of lateral onset as a factor in difference in visual field.", "content": "An experiment in matching judgments was designed to examine a role of perceptual process in apparent asymmetry. Recognition of Hirakana letters (Japanese letters) was required. The experimental condition in which stimuli were presented to the left visual field first and to the right visual field second produced more errors for all stimulus intervals (0 to 60 msec.) than experimental conditions where stimuli were presented to the right visual field first and to the left one second. Especially, superiority of the latter condition was marked with the longest stimulus interval employed. These results indicate superiority of the left hemisphere function for recognizing Hirakana letters and suggest that not only memory but also perceptual process contributes to this laterality effect.", "contents": "Asynchrony of lateral onset as a factor in difference in visual field. An experiment in matching judgments was designed to examine a role of perceptual process in apparent asymmetry. Recognition of Hirakana letters (Japanese letters) was required. The experimental condition in which stimuli were presented to the left visual field first and to the right visual field second produced more errors for all stimulus intervals (0 to 60 msec.) than experimental conditions where stimuli were presented to the right visual field first and to the left one second. Especially, superiority of the latter condition was marked with the longest stimulus interval employed. These results indicate superiority of the left hemisphere function for recognizing Hirakana letters and suggest that not only memory but also perceptual process contributes to this laterality effect."} {"id": "PMID:1256972", "title": "Dominant direction of conjugate lateral eye movements and responsiveness to facial and verbal cues.", "content": "Responsiveness to facial versus verbal cues as a function of dominant direction of conjugate lateral eye movements and sex was tested in a 2 X 2 analysis of variance design. Ss were 81 student volunteers. Right-movers (n = 33) were more responsive to verbal cues; left-movers (n = 45) were more responsive to facial cues (p less than .05). The results are consistent with the hypothesized link between conjugate lateral eye movements and functional asymmetry of the cerebral hemispheres. Males were more responsive to verbal cues; females were more responsive to facial cues (p less than .05). Data relevant to reliability of the eye movements, the relationship between sex and eye movements, and the relationship between type of question and eye movements are also presented.", "contents": "Dominant direction of conjugate lateral eye movements and responsiveness to facial and verbal cues. Responsiveness to facial versus verbal cues as a function of dominant direction of conjugate lateral eye movements and sex was tested in a 2 X 2 analysis of variance design. Ss were 81 student volunteers. Right-movers (n = 33) were more responsive to verbal cues; left-movers (n = 45) were more responsive to facial cues (p less than .05). The results are consistent with the hypothesized link between conjugate lateral eye movements and functional asymmetry of the cerebral hemispheres. Males were more responsive to verbal cues; females were more responsive to facial cues (p less than .05). Data relevant to reliability of the eye movements, the relationship between sex and eye movements, and the relationship between type of question and eye movements are also presented."} {"id": "PMID:1256973", "title": "Comparison of the methods of limits and electrodermal response for determination of lingual vibrotactile thresholds.", "content": "Lingual vibrotactile thresholds were obtained from 30 adult Ss by the method of limits and operant conditioning of the electrodermal response. Sensitivity of the tongue was measured at 250 Hz. Comparisons of lingual threshold data showed that thresholds obtained by the method of limits were significantly lower than those obtained by the electrodermal response technique. There was a moderate positive correlation between methods however, indicating a substantial relationship. It was concluded that consistent lingual vibrotactile indexes of sensitivity can be obtained using an electrodermal response approach.", "contents": "Comparison of the methods of limits and electrodermal response for determination of lingual vibrotactile thresholds. Lingual vibrotactile thresholds were obtained from 30 adult Ss by the method of limits and operant conditioning of the electrodermal response. Sensitivity of the tongue was measured at 250 Hz. Comparisons of lingual threshold data showed that thresholds obtained by the method of limits were significantly lower than those obtained by the electrodermal response technique. There was a moderate positive correlation between methods however, indicating a substantial relationship. It was concluded that consistent lingual vibrotactile indexes of sensitivity can be obtained using an electrodermal response approach."} {"id": "PMID:1256974", "title": "Monocular acquisition and interocular transfer in albino guinea pigs as mediated by ipsi- or contralateral fiber systems.", "content": "Monocular acquisition and interocular transfer of a horizontal-vertical discrimination were measured in 12 male albino guinea pigs with unilateral lesions of the striate cortex, and in 6 sham-operated controls. In accordance with electrophysiological and anatomical findings, the animals learned readily using the contralateral fibers, while the ipsilateral fibers were found to be incapable of mediating either acquisition, or retention, of the discrimination. The control animals learned readily, but showed incomplete transfer.", "contents": "Monocular acquisition and interocular transfer in albino guinea pigs as mediated by ipsi- or contralateral fiber systems. Monocular acquisition and interocular transfer of a horizontal-vertical discrimination were measured in 12 male albino guinea pigs with unilateral lesions of the striate cortex, and in 6 sham-operated controls. In accordance with electrophysiological and anatomical findings, the animals learned readily using the contralateral fibers, while the ipsilateral fibers were found to be incapable of mediating either acquisition, or retention, of the discrimination. The control animals learned readily, but showed incomplete transfer."} {"id": "PMID:1256976", "title": "Improving a cerbral palsied child's typing with operant techniques.", "content": "A 7-yr.-old cerebral palsied girl was taught to correct responses on two typing tasks using reinforcement contingent on number of correctly typed words. Maintenance of the behavior remained contingent on the presence of tangible reinforcement.", "contents": "Improving a cerbral palsied child's typing with operant techniques. A 7-yr.-old cerebral palsied girl was taught to correct responses on two typing tasks using reinforcement contingent on number of correctly typed words. Maintenance of the behavior remained contingent on the presence of tangible reinforcement."} {"id": "PMID:1256977", "title": "Intersubject variability in perceived oscillation as a function of threshold for binocular disparity.", "content": "Four groups of 15 female subjects each were classified along a quantitative dimension for proportion of perceived oscillation and threshold for binocular disparity. Analyses of variance showed that significant differences in proportion of perceived oscillation were accompanied by significant differences in threshold for binocular disparity for perceivers of \"high\" and \"low\" oscillation (p less than .05). For perceivers of \"intermediate\" oscillation significant differences in proportion of perceived oscillation but not threshold for binocular disparity were found. It was suggested that: (1) intersubject variability in perceived oscillation may be governed by the threshold for binocular disparity, (2) \"low\" perceivers may be especially sensitive to the magnitude of the cue, (3) \"intermediate\" perceivers' subjective reports may be primarily dependent on response criteria and the multiplicity of subjective factors which constitute it, (4) \"high\" perceivers apparently have least response sensitivity and they cannot maintain a consistent response criterion.", "contents": "Intersubject variability in perceived oscillation as a function of threshold for binocular disparity. Four groups of 15 female subjects each were classified along a quantitative dimension for proportion of perceived oscillation and threshold for binocular disparity. Analyses of variance showed that significant differences in proportion of perceived oscillation were accompanied by significant differences in threshold for binocular disparity for perceivers of \"high\" and \"low\" oscillation (p less than .05). For perceivers of \"intermediate\" oscillation significant differences in proportion of perceived oscillation but not threshold for binocular disparity were found. It was suggested that: (1) intersubject variability in perceived oscillation may be governed by the threshold for binocular disparity, (2) \"low\" perceivers may be especially sensitive to the magnitude of the cue, (3) \"intermediate\" perceivers' subjective reports may be primarily dependent on response criteria and the multiplicity of subjective factors which constitute it, (4) \"high\" perceivers apparently have least response sensitivity and they cannot maintain a consistent response criterion."} {"id": "PMID:1256978", "title": "Variations of Bender-Gestalt constriction and depression in adult psychiatric patients.", "content": "The present study explored variations of Bender-Gestalt constriction and their relation to depression. 20 Ss showing constriction of drawings on the upper half-page and 20 Ss showing constriction of drawings on the left half-page were compared with regard to MMPI Depression scores. No significant difference was found between these groups. However, when the constricted groups were combined and then compared with 40 Ss who did not show constriction of Bender drawings, the constricted group had significantly higher (p less than .05) MMPI Depression scores. Thus, variations in Bender constriction are not differently related to depression, but presence of constriction is an indicator. However, its rate of occurrence is so infrequent, appearing in only 5% of the records examined, that its clinical usefulness in the detection of depression is quite limited.", "contents": "Variations of Bender-Gestalt constriction and depression in adult psychiatric patients. The present study explored variations of Bender-Gestalt constriction and their relation to depression. 20 Ss showing constriction of drawings on the upper half-page and 20 Ss showing constriction of drawings on the left half-page were compared with regard to MMPI Depression scores. No significant difference was found between these groups. However, when the constricted groups were combined and then compared with 40 Ss who did not show constriction of Bender drawings, the constricted group had significantly higher (p less than .05) MMPI Depression scores. Thus, variations in Bender constriction are not differently related to depression, but presence of constriction is an indicator. However, its rate of occurrence is so infrequent, appearing in only 5% of the records examined, that its clinical usefulness in the detection of depression is quite limited."} {"id": "PMID:1256979", "title": "Note on duration of stimulus exposure in experiments on covert scanning of laterally shown targets.", "content": "Prevention of contamination by eye movements is on methodological requirement in the choice of an exposure time in experiments on the covert scanning of stimuli, tachistoscopically exposed laterally. The use of measures of eye movement latency to set upper limits for exposure intervals seems questionable because latency does not index the total time (minimally, 200 msec.) required to obtain information through an eye movement. The foregoing requirement, however, is only one consideration in selection of an exposure time. Since covert encoding processes can only function while the stimulus is on and during the after-stimulation, duration of exposure delimits the operating time of these processes. Choice of an interval, therefore, should establish the setting required to study those aspects of covert scanning of experimental interest.", "contents": "Note on duration of stimulus exposure in experiments on covert scanning of laterally shown targets. Prevention of contamination by eye movements is on methodological requirement in the choice of an exposure time in experiments on the covert scanning of stimuli, tachistoscopically exposed laterally. The use of measures of eye movement latency to set upper limits for exposure intervals seems questionable because latency does not index the total time (minimally, 200 msec.) required to obtain information through an eye movement. The foregoing requirement, however, is only one consideration in selection of an exposure time. Since covert encoding processes can only function while the stimulus is on and during the after-stimulation, duration of exposure delimits the operating time of these processes. Choice of an interval, therefore, should establish the setting required to study those aspects of covert scanning of experimental interest."} {"id": "PMID:1256980", "title": "The \"consciousness problem\" is not the problem.", "content": "Although the concept of consciousness is not necessary for the behavioral scientist, it is closely related to a number of psychological concepts that are generally believed to be necessary. Consciousness may be defined as the very short-term memory of a just-completed perceptual act. It may thus be understood as a psychological consequence of psychological antecedents. The question of how brain processes result in consciousness is a misleading one and should be replaced by questions concerning the relationships between the brain and perception, memory, and the other psychological processes that precede consciousness.", "contents": "The \"consciousness problem\" is not the problem. Although the concept of consciousness is not necessary for the behavioral scientist, it is closely related to a number of psychological concepts that are generally believed to be necessary. Consciousness may be defined as the very short-term memory of a just-completed perceptual act. It may thus be understood as a psychological consequence of psychological antecedents. The question of how brain processes result in consciousness is a misleading one and should be replaced by questions concerning the relationships between the brain and perception, memory, and the other psychological processes that precede consciousness."} {"id": "PMID:1256981", "title": "Future-time gradients for performance in test anxious individuals.", "content": "It was assumed that highly anxious individuals should have a negative goal gradient for future performance and that this negative goal gradient should be reduced as the test-anxiety dispositions of the individuals decreased. The results for 392 grade school (6th) students showed, as expected, that (a) the highly anxious individuals (n = 55) tended to decrease the number of problems solved correctly as a future goal (task) approached in time and that (b) the slopes of the negative goal gradients decreased as the test-anxiety dispositions decreased. When number of problems attempted was the measure of performance (c) ther was a tendency for Ss of low anxiety (n = 101) to increase their performance as the goal approached.", "contents": "Future-time gradients for performance in test anxious individuals. It was assumed that highly anxious individuals should have a negative goal gradient for future performance and that this negative goal gradient should be reduced as the test-anxiety dispositions of the individuals decreased. The results for 392 grade school (6th) students showed, as expected, that (a) the highly anxious individuals (n = 55) tended to decrease the number of problems solved correctly as a future goal (task) approached in time and that (b) the slopes of the negative goal gradients decreased as the test-anxiety dispositions decreased. When number of problems attempted was the measure of performance (c) ther was a tendency for Ss of low anxiety (n = 101) to increase their performance as the goal approached."} {"id": "PMID:1256982", "title": "Development of spatial concepts in visually deprived children.", "content": "110 blind children in Grades 2 through 12 were matched with sighted controls for age, sex, and verbal reasoning ability. Spatial reasoning was compared with nonspatial reasoning ability for the two groups. At each age level, blind children were inferior to sighted children on spatial reasoning, although the two groups did not differ on nonspatial reasoning. Data further support the likelihood that certain interactions with the perceptual environment may be crucial to specific aspects of cognitive functioning in humans.", "contents": "Development of spatial concepts in visually deprived children. 110 blind children in Grades 2 through 12 were matched with sighted controls for age, sex, and verbal reasoning ability. Spatial reasoning was compared with nonspatial reasoning ability for the two groups. At each age level, blind children were inferior to sighted children on spatial reasoning, although the two groups did not differ on nonspatial reasoning. Data further support the likelihood that certain interactions with the perceptual environment may be crucial to specific aspects of cognitive functioning in humans."} {"id": "PMID:1256983", "title": "Biofeedback training with a learning disabled child.", "content": "Biofeedback training was used to increase a learning disabled child's ability to control his breathing patterns. The procedure was most effective when the child was permitted to explore freely the correlations between his respiratory movements and feedback from the apparatus. Probe trials showed that increased external and self-directed control over the direction and volume of breathing was achieved. Results were discussed in terms of the relationship between biofeedback technology and learning and behavior problems.", "contents": "Biofeedback training with a learning disabled child. Biofeedback training was used to increase a learning disabled child's ability to control his breathing patterns. The procedure was most effective when the child was permitted to explore freely the correlations between his respiratory movements and feedback from the apparatus. Probe trials showed that increased external and self-directed control over the direction and volume of breathing was achieved. Results were discussed in terms of the relationship between biofeedback technology and learning and behavior problems."} {"id": "PMID:1256984", "title": "Discriminability and identifiability of the human hand based on its quantified complexity.", "content": "Photographs of human hands were quantified according to a method suggested by Attneave (1954). The over-all complexity of the hands' contours did not affect the accuracy with which pairs and non-pairs of hands could be discriminiated. However, significantly more errors were made in identifying the mates of hands whose thumb regions were relatively complex. These results suggest that the contours of nonlaboratory forms are quantifiable and amenable to parametric investigation.", "contents": "Discriminability and identifiability of the human hand based on its quantified complexity. Photographs of human hands were quantified according to a method suggested by Attneave (1954). The over-all complexity of the hands' contours did not affect the accuracy with which pairs and non-pairs of hands could be discriminiated. However, significantly more errors were made in identifying the mates of hands whose thumb regions were relatively complex. These results suggest that the contours of nonlaboratory forms are quantifiable and amenable to parametric investigation."} {"id": "PMID:1256985", "title": "Field dependence and distraction revisited.", "content": "An attempt is made to replicate a former study of the relationship of field dependence as measured by rod-and-frame errors to distraction in an RT paradigm. For two groups of Ss (n = 14) who differed specifically in their dependence upon the tilted frame and were classified as frame-dependent and frame-independent, no relationship of frame (or field) dependence to susceptibility to distraction was found.", "contents": "Field dependence and distraction revisited. An attempt is made to replicate a former study of the relationship of field dependence as measured by rod-and-frame errors to distraction in an RT paradigm. For two groups of Ss (n = 14) who differed specifically in their dependence upon the tilted frame and were classified as frame-dependent and frame-independent, no relationship of frame (or field) dependence to susceptibility to distraction was found."} {"id": "PMID:1256986", "title": "Interest in entering helping activities and self-disclosure to three targets on the Jourard self-disclosure scale.", "content": "Jourard's 40-item Self-disclosure Questionnaire was administered to 50 students in a training and selection program for a quasi-counseling position and 52 randomly selected students. Subjects indicated past disclosures to three target persons, parents, best friend, and stranger. Results indicated: highest disclosures were reported to best friends, lowest to strangers; subjects interested in the quasi-counseling position reported more disclosure than subjects not interested in this position; females reported more disclosure than males only to strangers.", "contents": "Interest in entering helping activities and self-disclosure to three targets on the Jourard self-disclosure scale. Jourard's 40-item Self-disclosure Questionnaire was administered to 50 students in a training and selection program for a quasi-counseling position and 52 randomly selected students. Subjects indicated past disclosures to three target persons, parents, best friend, and stranger. Results indicated: highest disclosures were reported to best friends, lowest to strangers; subjects interested in the quasi-counseling position reported more disclosure than subjects not interested in this position; females reported more disclosure than males only to strangers."} {"id": "PMID:1256987", "title": "Effects of incentive and preparatory interval on activity, heart rate, and reaction time in children.", "content": "To resolve certain empirical and theoretical difficulties concerning, primarily, the significance of phasic heart-rate deceleration prior to reaction signals, 48 children were employed to perform in simple reaction-time tasks while speed, heart rate, head movement, gross movement, and blink activity were recorded. The indeory intervals and level of incentives. Reaction time varied with incentive, with preparatory interval and mode of presentation. Phasic heart-rate deceleration varied with the intervals but not incentive or mode of presentation. There was little relation between deceleration and RT. Heart rate and somatic movement measures (especially of blinking) were roughly concordant at a group level but did not correlate.", "contents": "Effects of incentive and preparatory interval on activity, heart rate, and reaction time in children. To resolve certain empirical and theoretical difficulties concerning, primarily, the significance of phasic heart-rate deceleration prior to reaction signals, 48 children were employed to perform in simple reaction-time tasks while speed, heart rate, head movement, gross movement, and blink activity were recorded. The indeory intervals and level of incentives. Reaction time varied with incentive, with preparatory interval and mode of presentation. Phasic heart-rate deceleration varied with the intervals but not incentive or mode of presentation. There was little relation between deceleration and RT. Heart rate and somatic movement measures (especially of blinking) were roughly concordant at a group level but did not correlate."} {"id": "PMID:1256988", "title": "Parental correlates of Rorschach human movement responses in children.", "content": "The meaning of the human movement response (M) to inkblot stimuli was explored in terms of correlations between children's M productions and the attributes of their parents in 119 familes. M scores were available for the family members; and for each parent there were also measures of personality, values, and childrearing attitudes. A number of the parent-child correlational patterns were congruent with Rorschach's theories concerning the significance of M.", "contents": "Parental correlates of Rorschach human movement responses in children. The meaning of the human movement response (M) to inkblot stimuli was explored in terms of correlations between children's M productions and the attributes of their parents in 119 familes. M scores were available for the family members; and for each parent there were also measures of personality, values, and childrearing attitudes. A number of the parent-child correlational patterns were congruent with Rorschach's theories concerning the significance of M."} {"id": "PMID:1256989", "title": "Self-concept: a cross-cultural study.", "content": "Self-concept differences between 190 American and 98 Danish 5th and 6th grade suburban students were examined in light of known societal and educational differences. Danish males and American females reported significantly higher self-confidence in personal attributes; American students reported higher achieving in school scores than Danish students. Results are discussed in the contex of cultural differences; further areas of investigation are offered.", "contents": "Self-concept: a cross-cultural study. Self-concept differences between 190 American and 98 Danish 5th and 6th grade suburban students were examined in light of known societal and educational differences. Danish males and American females reported significantly higher self-confidence in personal attributes; American students reported higher achieving in school scores than Danish students. Results are discussed in the contex of cultural differences; further areas of investigation are offered."} {"id": "PMID:1256990", "title": "Effect of three levels of work intensity on performance of a fine motor skill.", "content": "The purpose of this study was to investigate the effect of three levels of work intensity on the performance of a fine motor skill during steady-state exercies. Subjects were administered a progressive bicycle ergometer test to exhaustion in order to determine maximum heart rate (HRmax). Following practice sessions on the pursuit rotor, subjects performed 3 different rides on a bicycle ergometer at 60, 75, and 90% of HRmax. The order to test administration was varied randomly in an attempt to control for sequential effects. Analysis of variance with repeated measures was used to determine differences in pursuit rotor performance by days and by levels of work intensity. No confounding of learning was noted. A significant F ratio (p less than .001) between work intensities showed that fine motor performance during steady-state exercise is affected by levels of work intensity.", "contents": "Effect of three levels of work intensity on performance of a fine motor skill. The purpose of this study was to investigate the effect of three levels of work intensity on the performance of a fine motor skill during steady-state exercies. Subjects were administered a progressive bicycle ergometer test to exhaustion in order to determine maximum heart rate (HRmax). Following practice sessions on the pursuit rotor, subjects performed 3 different rides on a bicycle ergometer at 60, 75, and 90% of HRmax. The order to test administration was varied randomly in an attempt to control for sequential effects. Analysis of variance with repeated measures was used to determine differences in pursuit rotor performance by days and by levels of work intensity. No confounding of learning was noted. A significant F ratio (p less than .001) between work intensities showed that fine motor performance during steady-state exercise is affected by levels of work intensity."} {"id": "PMID:1256992", "title": "Effects of social influence in a recognition task of auditory intensity: a temporary shift in criterion.", "content": "The effects of responses of another person or a computer occurring prior to the subjects' responses in tasks to recognition model which assumed that subjects shifted their decision criteria temporarily on each trial. A parameter representing the amount of criterion shift reliably estimated sensitivity to social influence. When the social sensitivity parameter was estimated from the data, discriminative ability, defined as d', was unaffected by the presence of social influence. Principal components analyses suggested that social sensitivity and discriminative ability represented essentially orthogonal components of subjects' decision behavior.", "contents": "Effects of social influence in a recognition task of auditory intensity: a temporary shift in criterion. The effects of responses of another person or a computer occurring prior to the subjects' responses in tasks to recognition model which assumed that subjects shifted their decision criteria temporarily on each trial. A parameter representing the amount of criterion shift reliably estimated sensitivity to social influence. When the social sensitivity parameter was estimated from the data, discriminative ability, defined as d', was unaffected by the presence of social influence. Principal components analyses suggested that social sensitivity and discriminative ability represented essentially orthogonal components of subjects' decision behavior."} {"id": "PMID:1257016", "title": "[Myocardial infarction in patients over 75 years old. Comparative macroscopic anatomical study].", "content": "The macroscopic anatomical study of 27 cases of patients aged over 75 years did not show any significant difference between the myocardial and established coronary artery lesions, and those of a numericaly related group of young subjects. These anatomical facts are inducive to take more into account the physiological age of patients, and not to statistically exclude certain old patients from the eventual benefit of therapy and full investigation, at present reserved for younger patients.", "contents": "[Myocardial infarction in patients over 75 years old. Comparative macroscopic anatomical study]. The macroscopic anatomical study of 27 cases of patients aged over 75 years did not show any significant difference between the myocardial and established coronary artery lesions, and those of a numericaly related group of young subjects. These anatomical facts are inducive to take more into account the physiological age of patients, and not to statistically exclude certain old patients from the eventual benefit of therapy and full investigation, at present reserved for younger patients."} {"id": "PMID:1257017", "title": "[Cecal perforations in the course of acute idiopathic distension of the colon].", "content": "On the basis of two fatal cases of perforation of the caecum secondary to dilatation of the colon without obstruction, the authors discuss the measures which should be instituted in the presence of this condition. These consist, preventively, of decompression of the colon by caecostomy if the diameter of the caecum reaches 10 cm and, curatively, a right hemi-colectomy, not associated with immediate re-establishment of the continuity of the digestive tract.", "contents": "[Cecal perforations in the course of acute idiopathic distension of the colon]. On the basis of two fatal cases of perforation of the caecum secondary to dilatation of the colon without obstruction, the authors discuss the measures which should be instituted in the presence of this condition. These consist, preventively, of decompression of the colon by caecostomy if the diameter of the caecum reaches 10 cm and, curatively, a right hemi-colectomy, not associated with immediate re-establishment of the continuity of the digestive tract."} {"id": "PMID:1257018", "title": "[Cholestatic hepatitis with a chronic course. 7 cases].", "content": "Cholestatic hepatitis, whilst having a longer course than cytolytic forms, in general regresses in a few months. The authors report here seven cases of cholestatic hepatitis lasting for more than 18 months. These chronic forms have certain characteristic features: - female predominance (6 cases out of 7). - a severe degree of cholestasis with, in particular, marked elevation of lipids, cholesterol and alkaline phosphatase. - the absence of Australia antibody and antigen, together with the absence of anti-smooth muscle antibody and anti-mitochondrial natibody. - a decrease in the number of permeable biliary canaliculi in the portal spaces. - a decrease in the number of permeable biliary canaliculi in the portal spaces. - a course which appears to be little influenced by various therapeutic measures. Although the final course seems satisfactory on the majority of cases, the possibility of a slow cirrhogenic transformation cannot be excluded in certain instances.", "contents": "[Cholestatic hepatitis with a chronic course. 7 cases]. Cholestatic hepatitis, whilst having a longer course than cytolytic forms, in general regresses in a few months. The authors report here seven cases of cholestatic hepatitis lasting for more than 18 months. These chronic forms have certain characteristic features: - female predominance (6 cases out of 7). - a severe degree of cholestasis with, in particular, marked elevation of lipids, cholesterol and alkaline phosphatase. - the absence of Australia antibody and antigen, together with the absence of anti-smooth muscle antibody and anti-mitochondrial natibody. - a decrease in the number of permeable biliary canaliculi in the portal spaces. - a decrease in the number of permeable biliary canaliculi in the portal spaces. - a course which appears to be little influenced by various therapeutic measures. Although the final course seems satisfactory on the majority of cases, the possibility of a slow cirrhogenic transformation cannot be excluded in certain instances."} {"id": "PMID:1257020", "title": "[Sensitization to penicillin following cutaneous side-effects of ampicillin].", "content": "Sensitization to penicillin was determined in vitro in twenty subjects, 30 days after cutaneous side-effects due to ampicillin. The study inclued the detection of anti-penicillin IgE, IgM, a lymphoblastic transformation test and a leucocyte migration test. No difference could be demonstrated between the sensitization 30 days after an ampicillin reaction and the sensitization 30 days after a penicillin reaction.", "contents": "[Sensitization to penicillin following cutaneous side-effects of ampicillin]. Sensitization to penicillin was determined in vitro in twenty subjects, 30 days after cutaneous side-effects due to ampicillin. The study inclued the detection of anti-penicillin IgE, IgM, a lymphoblastic transformation test and a leucocyte migration test. No difference could be demonstrated between the sensitization 30 days after an ampicillin reaction and the sensitization 30 days after a penicillin reaction."} {"id": "PMID:1257034", "title": "[The half-life of iodine 131-labelled fibrinogen in cancer patients. Effects of heparin].", "content": "Sixty nine patients suffering from malignant tumours at different stages of their development underwent a kinetic study of fibrinogen 131I with external counting over the tumour and a study of haemostasis including P.D.F. The 1/2 T of fibrinogen 131I is shortened: 2.52 +/- 0.09 days (normal: 3.89 +/- 0.11 days.) The abnormality is proportional to serum P.D.F. levels (r=0.99). External counting demonstrated the uptake of labelled fibrinogen in the tumour. Heparine (15000 U/24h) restores the 1/2 T of fibrinogen to normal in 95 p. cent of cases. The results suggest the existence of a localised compensated intravascular coagulation process inside the tumour. Possible consequences of that phenomenon are discussed.", "contents": "[The half-life of iodine 131-labelled fibrinogen in cancer patients. Effects of heparin]. Sixty nine patients suffering from malignant tumours at different stages of their development underwent a kinetic study of fibrinogen 131I with external counting over the tumour and a study of haemostasis including P.D.F. The 1/2 T of fibrinogen 131I is shortened: 2.52 +/- 0.09 days (normal: 3.89 +/- 0.11 days.) The abnormality is proportional to serum P.D.F. levels (r=0.99). External counting demonstrated the uptake of labelled fibrinogen in the tumour. Heparine (15000 U/24h) restores the 1/2 T of fibrinogen to normal in 95 p. cent of cases. The results suggest the existence of a localised compensated intravascular coagulation process inside the tumour. Possible consequences of that phenomenon are discussed."} {"id": "PMID:1257043", "title": "Uptake of 99mTc-tripolyphosphate in thrombotic leg.", "content": "Thirtyeight patients with suspected thrombosis in the legs were investigated scintigraphically using 99mTc-tripolyphosphate. The ratio between the activity in the leg with suspected thrombosis and the other leg was calculated. The results were compared with those obtained with phlebography. A pathologically high activity ratio was found in all but one of the 18 patients in whom phlebography showed a thrombus. The ratio was normal in 13 of the 20 patients with normal phlebographic findings. The possible use of the method described as a postoperative screening test is discussed.", "contents": "Uptake of 99mTc-tripolyphosphate in thrombotic leg. Thirtyeight patients with suspected thrombosis in the legs were investigated scintigraphically using 99mTc-tripolyphosphate. The ratio between the activity in the leg with suspected thrombosis and the other leg was calculated. The results were compared with those obtained with phlebography. A pathologically high activity ratio was found in all but one of the 18 patients in whom phlebography showed a thrombus. The ratio was normal in 13 of the 20 patients with normal phlebographic findings. The possible use of the method described as a postoperative screening test is discussed."} {"id": "PMID:1257044", "title": "[Dependence of regional lung function on posture: radiospirometric findings in health].", "content": "Ten healthy volunteers were examined radiospirometrically using 133Xenon in physiologic saline i.v. and with 133Xenon gas inhalation. The measurements were done using a gamma camera (Nuclear Chicago, Pho/Gamma III) in the PA projection in both sitting and supine positions. For evaluation, each lung was divided into three regions: upper, middle, and lower fields. Using a computer (DEC, GAMMA 11), the minute exhalation value, the perfusion and ventilation indices, and the ventilation/perfusion quotient were calculated. In the upright position the ventilation and perfusion indices increase from cranial to caudal. In the horizontal position the regional lung functions tend to equalize. The vital capacity is larger in the vertical position than in the horizontal position, particularly in the right lung. The values are shown in tabular form.", "contents": "[Dependence of regional lung function on posture: radiospirometric findings in health]. Ten healthy volunteers were examined radiospirometrically using 133Xenon in physiologic saline i.v. and with 133Xenon gas inhalation. The measurements were done using a gamma camera (Nuclear Chicago, Pho/Gamma III) in the PA projection in both sitting and supine positions. For evaluation, each lung was divided into three regions: upper, middle, and lower fields. Using a computer (DEC, GAMMA 11), the minute exhalation value, the perfusion and ventilation indices, and the ventilation/perfusion quotient were calculated. In the upright position the ventilation and perfusion indices increase from cranial to caudal. In the horizontal position the regional lung functions tend to equalize. The vital capacity is larger in the vertical position than in the horizontal position, particularly in the right lung. The values are shown in tabular form."} {"id": "PMID:1257045", "title": "[Isotope studies of cerebral circulation using the Fucks-Knipping gamma camera: use of a multi-parameter system with an intravenous tracer injection technic].", "content": "In order to analyze cerebral blood flow for diagnostic purposes, Indium 113m-DTPA was i.v. injected into seated patients, and time-activity curves were registered by a multifacet gamma camera (Fucks-Knipping) from 8 regions of interest, from the median area and from the right and left side of the head: 3 from the hemisphere, 3 from the brain stem, 2 from the large arteries of the neck. The results from 14 patients with chronic impairment of cerebral blood flow were compared with normal data from 20 healthy individuals. The time activity curves were analyzed for peak-height, mean transit time, and ratio peak to plateau height. The individual parameters were investigated for the degree of their correlation in a multiparameter system. The results from the patients indicated for the different single parameters a non-uniform response. There was also no correlation between the deviation of different parameters, between single pathological parameters and the degree and the site of blood flow impairment. On the other hand, a positive correlation was found between the number of pathological parameters and the degree of blood flow impairment irrespective of the site of its localization. Reason for this result probably is the variable location and degree of blood flow compensation by collaterals, which predominantly are expected at the cerebral base. The data indicate the potential usefulness of the application of the multiparameter analysis to quantitatively detect the degree of impairment of cerebral blood flow without regard to its topography. In this respect, the method, here described, promises to be of clinical value for non-invasive and non-hazardous diagnostic screening of cerebral blood flow.", "contents": "[Isotope studies of cerebral circulation using the Fucks-Knipping gamma camera: use of a multi-parameter system with an intravenous tracer injection technic]. In order to analyze cerebral blood flow for diagnostic purposes, Indium 113m-DTPA was i.v. injected into seated patients, and time-activity curves were registered by a multifacet gamma camera (Fucks-Knipping) from 8 regions of interest, from the median area and from the right and left side of the head: 3 from the hemisphere, 3 from the brain stem, 2 from the large arteries of the neck. The results from 14 patients with chronic impairment of cerebral blood flow were compared with normal data from 20 healthy individuals. The time activity curves were analyzed for peak-height, mean transit time, and ratio peak to plateau height. The individual parameters were investigated for the degree of their correlation in a multiparameter system. The results from the patients indicated for the different single parameters a non-uniform response. There was also no correlation between the deviation of different parameters, between single pathological parameters and the degree and the site of blood flow impairment. On the other hand, a positive correlation was found between the number of pathological parameters and the degree of blood flow impairment irrespective of the site of its localization. Reason for this result probably is the variable location and degree of blood flow compensation by collaterals, which predominantly are expected at the cerebral base. The data indicate the potential usefulness of the application of the multiparameter analysis to quantitatively detect the degree of impairment of cerebral blood flow without regard to its topography. In this respect, the method, here described, promises to be of clinical value for non-invasive and non-hazardous diagnostic screening of cerebral blood flow."} {"id": "PMID:1257046", "title": "Specific diagnosis of brain disease with double isotope brain scanning.", "content": "25 patients with known cerebral disease (either CVA's or primary or secondary tumours) diagnosed by clinical and angiographic criteria were submitted to a double isotope imaging technique using 99mTcO4- and 99mTc-EHDP. The different biological behaviour of these radiopharmaceuticals has provided specific and differential diagnosis between vascular and neoplastic disease of the brain. 99mTc-EHDP is shown to be the tracer of choice for the imaging of CVA's and 99mTcO4- is confirmed as the tracer of choice for the imaging of primary or secondary tumours in the brain.", "contents": "Specific diagnosis of brain disease with double isotope brain scanning. 25 patients with known cerebral disease (either CVA's or primary or secondary tumours) diagnosed by clinical and angiographic criteria were submitted to a double isotope imaging technique using 99mTcO4- and 99mTc-EHDP. The different biological behaviour of these radiopharmaceuticals has provided specific and differential diagnosis between vascular and neoplastic disease of the brain. 99mTc-EHDP is shown to be the tracer of choice for the imaging of CVA's and 99mTcO4- is confirmed as the tracer of choice for the imaging of primary or secondary tumours in the brain."} {"id": "PMID:1257047", "title": "Scintigraphic demonstration of amebic liver abscesses with 131iodine labeled bromometronidazole.", "content": "This case report demonstrates an hepatic amebic abscess by scintigraphy, utilizing a new radiopharmaceutical designed specifically for that purpose. The abscess is delineated as a positive lesion after twenty four hours. The agent 131I-labeled bromometronidazole, may prove to be specific for the diagnosis of these abscesses.", "contents": "Scintigraphic demonstration of amebic liver abscesses with 131iodine labeled bromometronidazole. This case report demonstrates an hepatic amebic abscess by scintigraphy, utilizing a new radiopharmaceutical designed specifically for that purpose. The abscess is delineated as a positive lesion after twenty four hours. The agent 131I-labeled bromometronidazole, may prove to be specific for the diagnosis of these abscesses."} {"id": "PMID:1257048", "title": "[131-I cholesterol (19-C) in the functional and localization diagnosis of adrenal cortex disorders].", "content": "Results are reported of quantitative adrenal scintigraphy with 131I-cholesterol in 8 patients with normal adrenal function before and after ACTH-stimulation and cortisol-suppression respectively, in one case with an adrenal metastasis from a pulmonary cancer, in two cases with Cushing's disease and in 7 cases with Conn's disease. In normal cases and in patients with M. Cushing a diagnosis of adrenal cortical function is possible with this method but can usually be replaced by more specific biochemical studies of serum and urine. The scintigraphic method is in addition of value in localization studies and can in unequivocal cases replace the selective adrenal phlebography. In patients with M. Conn increased uptake values (bilateral adrenal cortex hyperplasia) as well as reduced or non-detectable uptakes were observed, one of these cases suffering from a cortex carcinoma with M. Conn.", "contents": "[131-I cholesterol (19-C) in the functional and localization diagnosis of adrenal cortex disorders]. Results are reported of quantitative adrenal scintigraphy with 131I-cholesterol in 8 patients with normal adrenal function before and after ACTH-stimulation and cortisol-suppression respectively, in one case with an adrenal metastasis from a pulmonary cancer, in two cases with Cushing's disease and in 7 cases with Conn's disease. In normal cases and in patients with M. Cushing a diagnosis of adrenal cortical function is possible with this method but can usually be replaced by more specific biochemical studies of serum and urine. The scintigraphic method is in addition of value in localization studies and can in unequivocal cases replace the selective adrenal phlebography. In patients with M. Conn increased uptake values (bilateral adrenal cortex hyperplasia) as well as reduced or non-detectable uptakes were observed, one of these cases suffering from a cortex carcinoma with M. Conn."} {"id": "PMID:1257049", "title": "Transcription of the nonrepeated fraction of \"accessible\" DNA in rat liver chromatin.", "content": "The relationship between structure and function in eukaryotic chromatin has been studied in rat liver cells. To elucidate the functional significance of \"accessible\" DNA, the transcription of this DNA (prepared by titration of liver chromatin with poly-D-lysine) has been examined by RNA-DNA hybridization. The maximum extent to which nuclear RNA will hybridize to the nonrepeated fraction of \"accessible\" DNA has been measured and compared to the extent that whole chromatin DNA will hybridize. The results show that \"accessible\" DNA has the same number of sequences complementary to nuclear RNA as does total DNA. In addition DNA-DNA reassociation experiments indicate that there is only a small difference between the total unique sequence populations of \"accessible\" and total DNA. These results indicate that nonrepeated \"accessible\" DNA is not preferentially transcribed in the cell as is predicted by some models of chromatin structure.", "contents": "Transcription of the nonrepeated fraction of \"accessible\" DNA in rat liver chromatin. The relationship between structure and function in eukaryotic chromatin has been studied in rat liver cells. To elucidate the functional significance of \"accessible\" DNA, the transcription of this DNA (prepared by titration of liver chromatin with poly-D-lysine) has been examined by RNA-DNA hybridization. The maximum extent to which nuclear RNA will hybridize to the nonrepeated fraction of \"accessible\" DNA has been measured and compared to the extent that whole chromatin DNA will hybridize. The results show that \"accessible\" DNA has the same number of sequences complementary to nuclear RNA as does total DNA. In addition DNA-DNA reassociation experiments indicate that there is only a small difference between the total unique sequence populations of \"accessible\" and total DNA. These results indicate that nonrepeated \"accessible\" DNA is not preferentially transcribed in the cell as is predicted by some models of chromatin structure."} {"id": "PMID:1257050", "title": "Studies on the mechanism of DNA cleavage by ethidium.", "content": "Ethidium causes the cleavage of DNA via a light and oxygen dependent process. Using covalently closed circular DNA as a substrate, the saturation kinetics and the dependence on superhelical density of the cleavage indicate that intercalated ethidium is mainly responsible for nicking DNA. Superoxide dismutase has little effect on the reaction and catalase none. Lowering the pH inhibited the reaction. The reaction mechanism and its use in determining superhelical densities of covalently closed circular DNA's are discussed.", "contents": "Studies on the mechanism of DNA cleavage by ethidium. Ethidium causes the cleavage of DNA via a light and oxygen dependent process. Using covalently closed circular DNA as a substrate, the saturation kinetics and the dependence on superhelical density of the cleavage indicate that intercalated ethidium is mainly responsible for nicking DNA. Superoxide dismutase has little effect on the reaction and catalase none. Lowering the pH inhibited the reaction. The reaction mechanism and its use in determining superhelical densities of covalently closed circular DNA's are discussed."} {"id": "PMID:1257051", "title": "A conformational study of adenylyl-(3',5')-adenosine and adenylyl-(2',5')-adenosine in aqueous solution by carbon-13 magnetic resonance spectroscopy.", "content": "The solution conformation of adenylyl-(3',5')-adenosine and adenylyl-(2',5')-adenosine in both the stacked and unstacked states was studied by carbon-13 magnetic resonance spectroscopy. Large chemical shift differences between the base carbons in the dimers and those in the corresponding monomers are attributed in part to the influence of base-base interaction. Carbon-phosphorus couplings across three bonds revealed the preferred populations for certain backbone rotamers, demonstrating that significant changes in conformation about the \"c(3')-O and C(5')-O bonds do not occur in the temperature or salt-induced unstacking of adenylyl-(3',5')-adenosine. However, rotations about the C(2')-O and C(5')-O bonds occur in the temperature-mediated unstacking of adenylyl-(2',5')-adenosine.", "contents": "A conformational study of adenylyl-(3',5')-adenosine and adenylyl-(2',5')-adenosine in aqueous solution by carbon-13 magnetic resonance spectroscopy. The solution conformation of adenylyl-(3',5')-adenosine and adenylyl-(2',5')-adenosine in both the stacked and unstacked states was studied by carbon-13 magnetic resonance spectroscopy. Large chemical shift differences between the base carbons in the dimers and those in the corresponding monomers are attributed in part to the influence of base-base interaction. Carbon-phosphorus couplings across three bonds revealed the preferred populations for certain backbone rotamers, demonstrating that significant changes in conformation about the \"c(3')-O and C(5')-O bonds do not occur in the temperature or salt-induced unstacking of adenylyl-(3',5')-adenosine. However, rotations about the C(2')-O and C(5')-O bonds occur in the temperature-mediated unstacking of adenylyl-(2',5')-adenosine."} {"id": "PMID:1257052", "title": "Preparation of pancreatic mRNA: cell-free translation of an insulin-immunoreactive polypeptide.", "content": "Total nucleic acid extraction and selection of poly A-containing molecules yield preparative quantities of undegraded mRNA from adult and fetal pancreas. Using a stringent immunoassay, this mRNA is found to direct the synthesis of an immunoreactive insulin polypeptide in the wheat germ translation system. On sodium dodecyl sulfate polyacrylamide gels, this polypeptide (12,000-13,000 daltons) is larger than proinsulin (9,000 daltons).", "contents": "Preparation of pancreatic mRNA: cell-free translation of an insulin-immunoreactive polypeptide. Total nucleic acid extraction and selection of poly A-containing molecules yield preparative quantities of undegraded mRNA from adult and fetal pancreas. Using a stringent immunoassay, this mRNA is found to direct the synthesis of an immunoreactive insulin polypeptide in the wheat germ translation system. On sodium dodecyl sulfate polyacrylamide gels, this polypeptide (12,000-13,000 daltons) is larger than proinsulin (9,000 daltons)."} {"id": "PMID:1257053", "title": "Biosynthesis of the modified nucleoside Q in transfer RNA.", "content": "During biosynthesis of the modified nucleoside Q, 7-(4,5-DIHYDROXYL-1-1-CYCLOPENTEN-3-YL-AMINOMETHYL)-7-DEAZAGUANOSINE, IN TRNA, the carbon atom at position 8 in precursor molecule guanine was expelled together with the nitrogen atom N-7 in a fashion similar to that in the biosynthesis of the nucleoside antibiotic toyocamycin.", "contents": "Biosynthesis of the modified nucleoside Q in transfer RNA. During biosynthesis of the modified nucleoside Q, 7-(4,5-DIHYDROXYL-1-1-CYCLOPENTEN-3-YL-AMINOMETHYL)-7-DEAZAGUANOSINE, IN TRNA, the carbon atom at position 8 in precursor molecule guanine was expelled together with the nitrogen atom N-7 in a fashion similar to that in the biosynthesis of the nucleoside antibiotic toyocamycin."} {"id": "PMID:1257054", "title": "Circular dichroism calculations for polyinosinic acid in proposed multi-stranded geometries.", "content": "Circular dichroism spectra have been calculated for multi-stranded polyinosinic acid using three different right-handed structures proposed from X-ray diffraction studies. Agreement between calculated spectra and spectra measured at high salt concentration is best for a four strand structure in which the bases are tilted with respect to the helix axis, as proposed by Arnott et al. (1974). For structures in which the bases are perpendicular to the helix axis, the characteristic negative circular dichoroism of polyinosinic acid at long wavelength no longer appears in the calculated spectra. It is clear that a negative circular dichroism at long wavelength does not indicate a left-handed polynucleotide helix.", "contents": "Circular dichroism calculations for polyinosinic acid in proposed multi-stranded geometries. Circular dichroism spectra have been calculated for multi-stranded polyinosinic acid using three different right-handed structures proposed from X-ray diffraction studies. Agreement between calculated spectra and spectra measured at high salt concentration is best for a four strand structure in which the bases are tilted with respect to the helix axis, as proposed by Arnott et al. (1974). For structures in which the bases are perpendicular to the helix axis, the characteristic negative circular dichoroism of polyinosinic acid at long wavelength no longer appears in the calculated spectra. It is clear that a negative circular dichroism at long wavelength does not indicate a left-handed polynucleotide helix."} {"id": "PMID:1257055", "title": "Reaction of HeLa cell methyl-labelled 28S ribosomal RNA with sodium bisulphite: a conformational probe for methylated sequences.", "content": "The reaction of 14C methyl-labelled HeLa cell 28 S ribosomal RNA with sodium bisulphite was studied. Using conditions under which 30% of the total cytidine residues were de-aminated to uridine, the reactivities of individual cytidine residues near particular methylation sites differed widely; some underwent almost quantitative reaction, some showed intermediate reactivity and others were almost inert. The possible value of this method as a conformational probe for ribosomal RNA is discussed.", "contents": "Reaction of HeLa cell methyl-labelled 28S ribosomal RNA with sodium bisulphite: a conformational probe for methylated sequences. The reaction of 14C methyl-labelled HeLa cell 28 S ribosomal RNA with sodium bisulphite was studied. Using conditions under which 30% of the total cytidine residues were de-aminated to uridine, the reactivities of individual cytidine residues near particular methylation sites differed widely; some underwent almost quantitative reaction, some showed intermediate reactivity and others were almost inert. The possible value of this method as a conformational probe for ribosomal RNA is discussed."} {"id": "PMID:1257056", "title": "On the isolation of TI-plasmid from Agrobacterium tumefaciens.", "content": "An efficient lysis method for Agrobacterium cells was developed, which allows a reproducible isolation of the tumor inducing (TI)-plasmid. The lysis method is based on the sensitivity of this bacterium to incubation with lysozyme, n-dodecylamine,EDTA, followed by Sarkosyl, after growth in the presence of carbenicillin. We also present a procedure for the isolation of the TI-plasmid on a large scale, that might be used for the mass isolation of other large plasmids which like the TI-plasmid, can not be cleared with earlier described procedures. The purity of the plasmid preparations was determined with DNA renaturation kinetics, which method has the advantage that the plasmid need not to be in the supercoiled or open circular form.", "contents": "On the isolation of TI-plasmid from Agrobacterium tumefaciens. An efficient lysis method for Agrobacterium cells was developed, which allows a reproducible isolation of the tumor inducing (TI)-plasmid. The lysis method is based on the sensitivity of this bacterium to incubation with lysozyme, n-dodecylamine,EDTA, followed by Sarkosyl, after growth in the presence of carbenicillin. We also present a procedure for the isolation of the TI-plasmid on a large scale, that might be used for the mass isolation of other large plasmids which like the TI-plasmid, can not be cleared with earlier described procedures. The purity of the plasmid preparations was determined with DNA renaturation kinetics, which method has the advantage that the plasmid need not to be in the supercoiled or open circular form."} {"id": "PMID:1257057", "title": "Heterogeneity of chromatin subunits in vitro and location of histone H1.", "content": "Chromatin subunits (\"nucleosomes\") which were purified by sucrose gradient centrifugation of a staphylococcal nuclease digest of chromatin have been studied. We found that such a preparation contains nucleosomes of two discrete types which can be separated from each other by polyacrylamide gel electrophoresis. Nucleosome of the first type contains all five histones and a DNA segment of approximately 200 base pairs long, whereas nucleosome of the second type lacks histone H1 and its DNA segment is approximately 170 base pairs long, i.e., about 30 base pairs shorter than the DNA segment of the nucleosome of the first type. Purified dimer of the nucleosome also can be fractionated by gel electrophoresis into three discrete bands which correspond to dinucleosomes containing two molecules of histone H1, one and no H1. These and related findings strongly suggest that the H1 molecule is bound to a short (approximately 30 base pairs) terminal stretch of the nucleosomal DNA segment which can be removed by nuclease (possibly in the form of H1-DNA complex) without any significant disturbance of main structural features of the nucleosome.", "contents": "Heterogeneity of chromatin subunits in vitro and location of histone H1. Chromatin subunits (\"nucleosomes\") which were purified by sucrose gradient centrifugation of a staphylococcal nuclease digest of chromatin have been studied. We found that such a preparation contains nucleosomes of two discrete types which can be separated from each other by polyacrylamide gel electrophoresis. Nucleosome of the first type contains all five histones and a DNA segment of approximately 200 base pairs long, whereas nucleosome of the second type lacks histone H1 and its DNA segment is approximately 170 base pairs long, i.e., about 30 base pairs shorter than the DNA segment of the nucleosome of the first type. Purified dimer of the nucleosome also can be fractionated by gel electrophoresis into three discrete bands which correspond to dinucleosomes containing two molecules of histone H1, one and no H1. These and related findings strongly suggest that the H1 molecule is bound to a short (approximately 30 base pairs) terminal stretch of the nucleosomal DNA segment which can be removed by nuclease (possibly in the form of H1-DNA complex) without any significant disturbance of main structural features of the nucleosome."} {"id": "PMID:1257058", "title": "Basic polypeptides as histone models. Effect of conformation, base composition and methylation of nucleic acids on the interaction with H1 and histone models and on the circular dichroism of complexes.", "content": "Interaction of histone H 1 and models simulating histone chains was followed by monitoring the melting curves of supernatants after the sedimentation of aggregated complexes. In a mixture of two DNAs the histones reacted selectively with (A+T)-rich and non-methylated DNA, respectively. H 1 and (Ala-Lys-Pro)n also interacted preferentially with DNA in a mixture with double stranded RNA whereas (Lys30,Ala70)n did not show any selectivity. (G+C)-rich DNA in complexes showed CD spectra the intensity of which decreased with increasing DNA methylation to values comparable with these of complexes of (A+T)-rich DNA. In complexed with double stranded RNA only the polymer (Lys30,Ala70) displayed CD pattern similar to spectra of complexes with DNA. It was concluded that formation and structure of complexes depend selectively on the DNA conformation and base composition.", "contents": "Basic polypeptides as histone models. Effect of conformation, base composition and methylation of nucleic acids on the interaction with H1 and histone models and on the circular dichroism of complexes. Interaction of histone H 1 and models simulating histone chains was followed by monitoring the melting curves of supernatants after the sedimentation of aggregated complexes. In a mixture of two DNAs the histones reacted selectively with (A+T)-rich and non-methylated DNA, respectively. H 1 and (Ala-Lys-Pro)n also interacted preferentially with DNA in a mixture with double stranded RNA whereas (Lys30,Ala70)n did not show any selectivity. (G+C)-rich DNA in complexes showed CD spectra the intensity of which decreased with increasing DNA methylation to values comparable with these of complexes of (A+T)-rich DNA. In complexed with double stranded RNA only the polymer (Lys30,Ala70) displayed CD pattern similar to spectra of complexes with DNA. It was concluded that formation and structure of complexes depend selectively on the DNA conformation and base composition."} {"id": "PMID:1257213", "title": "[Changes in the cerebral electrical activity of Itsenko-Cushing disease patients under the influence of diphenine].", "content": "For the purpose of studying the functional condition of the CNS the authors recorded the electrical activity of the brain (by the method of electroencephalography) in parallel with determination of the adrenal cortex function in patients with Itsenko-Cushing disease to whom diphenin was prescribed. Results of investigations showed reduction of the adrenal cortex function in patients with Itsenko-Cushing disease under the effect of diphenin to occur in parallel with reduction of irritation in the brain structures, detected by EEG. The data obtained confirmed an important role played by disturbances of the nervous regulation mechanisms in the appearance of this pathology.", "contents": "[Changes in the cerebral electrical activity of Itsenko-Cushing disease patients under the influence of diphenine]. For the purpose of studying the functional condition of the CNS the authors recorded the electrical activity of the brain (by the method of electroencephalography) in parallel with determination of the adrenal cortex function in patients with Itsenko-Cushing disease to whom diphenin was prescribed. Results of investigations showed reduction of the adrenal cortex function in patients with Itsenko-Cushing disease under the effect of diphenin to occur in parallel with reduction of irritation in the brain structures, detected by EEG. The data obtained confirmed an important role played by disturbances of the nervous regulation mechanisms in the appearance of this pathology."} {"id": "PMID:1257212", "title": "[The influence of adrenal cortical hormones on the state of the kinin system].", "content": "Condition of the kinin system proved to depend on the function of the adrenal cortex. An excess of glucocorticoids decreased the activity of the kinin system of the blood and kidneys. The activity of the kinin system of the blood increased in hypocorticism, whereas in the kidneys there was seen a reduction of kallikrein formation.", "contents": "[The influence of adrenal cortical hormones on the state of the kinin system]. Condition of the kinin system proved to depend on the function of the adrenal cortex. An excess of glucocorticoids decreased the activity of the kinin system of the blood and kidneys. The activity of the kinin system of the blood increased in hypocorticism, whereas in the kidneys there was seen a reduction of kallikrein formation."} {"id": "PMID:1257216", "title": "[The influence of different factors on the incidence of diabetes mellitus among the population of Ulan-Ude].", "content": "The authors present the results of studying the effect of the social-hygienic factors in diabetes mellitus morbidity in the population of Ulan-Ude. Comparative analysis of the influence of the social-hygienic factors on diabetes mellitus morbidity showed that in men origination of diabetes mellitus was promoted primarily by nervous strain during work and intensive smoking; derangements in nutritional hygiene were of lesser significance. In women origination of diabetes mellitus was primarily promoted by derangements in nutrional hygiene and emotions connected with their family; work accompanied by marked nervous strain played a lesser role.", "contents": "[The influence of different factors on the incidence of diabetes mellitus among the population of Ulan-Ude]. The authors present the results of studying the effect of the social-hygienic factors in diabetes mellitus morbidity in the population of Ulan-Ude. Comparative analysis of the influence of the social-hygienic factors on diabetes mellitus morbidity showed that in men origination of diabetes mellitus was promoted primarily by nervous strain during work and intensive smoking; derangements in nutritional hygiene were of lesser significance. In women origination of diabetes mellitus was primarily promoted by derangements in nutrional hygiene and emotions connected with their family; work accompanied by marked nervous strain played a lesser role."} {"id": "PMID:1257215", "title": "[Urinary aldosterone excretion and erythrocyte and plasma sodium and potassium ion concentration in persons of different ages].", "content": "Practically healthy persons (79 in all) aged from 20 to 80 years and over were examined. The work was aimed at the study of the character of aldosterone excretion and its correlation with the ionic composition of erythrocytes and the peripheral blood plasma in persons at various age periods. As revealed, the activity of glomerular zone of the adrenal cortex in persons aged from 20 to 40 years displayed sexual differences: 1.33 times more aldosterone was excreted with the urine in women than in men. With the advance of age there occurred a functional decrease in the glomerular zone of the adrenal cortex. In senile persons (aged 80 years and over) this difference was entirely eliminated. Sodium ions in erythrocytes increased, but remained unchanged in the peripheral blood plasma. Potassium ion concentration fell both in the erythrocytes and in the blood plasma. A reduction of aldosterone content failed to alter the sodium-retention effect of its action which corresponded to the concept on increase of tissue sensitivity to hormones with the advance of age.", "contents": "[Urinary aldosterone excretion and erythrocyte and plasma sodium and potassium ion concentration in persons of different ages]. Practically healthy persons (79 in all) aged from 20 to 80 years and over were examined. The work was aimed at the study of the character of aldosterone excretion and its correlation with the ionic composition of erythrocytes and the peripheral blood plasma in persons at various age periods. As revealed, the activity of glomerular zone of the adrenal cortex in persons aged from 20 to 40 years displayed sexual differences: 1.33 times more aldosterone was excreted with the urine in women than in men. With the advance of age there occurred a functional decrease in the glomerular zone of the adrenal cortex. In senile persons (aged 80 years and over) this difference was entirely eliminated. Sodium ions in erythrocytes increased, but remained unchanged in the peripheral blood plasma. Potassium ion concentration fell both in the erythrocytes and in the blood plasma. A reduction of aldosterone content failed to alter the sodium-retention effect of its action which corresponded to the concept on increase of tissue sensitivity to hormones with the advance of age."} {"id": "PMID:1257217", "title": "[The relationship between the pineal gland and the hypothalamo-hypophyseal complex. I. The effect of pinealectomy, binding and continuous illumination on H3-leucine incorporation in the nucleus of the anterior, middle and posterior hypothalamus of prepubertal and sexually mature rats].", "content": "Autoradiography was applied to the study of the effect of extirpation of the epiphysis in rats on the level of H3-leucine incorporation by the neurons of 8 couples of the nuclei localized in the anterior, middle and posterior portions of the hypothalamus. Experiments were conducted on female animals of the prepubertal and reproductive age. Pinealectomy was combined with binding (a factor intensifying the physiological status of the epiphysis) and continuous illumination (a factor inhibiting the function of this gland). In the blinded prepubertal rats pinealectomy enhanced the H3-leucine incorporation into the supraoptic nucleus by 38%, into the paraventricular--by 26%, into the dorsomedial--by 61%, into the premammillary dorsal--by 58%, into the ventro-medial--by 40%, into the premammillary ventral--by 36%, and into the anterior hypothalamic--by 26%. In mature rats this index exceeded, after pinealectomy, such in the sham-operated animals (control) in the supraoptic nucleus by 48%, in the paraventral--by 40%, in the premamillary ventral--by 80%, in the arcuate--by 48%, in the premammillary dorsal--by 35%, in the ventro-medial--by 29%, and in the dorso-medial--by 26%. Continuous illumination reduced the stimulating influence of pinealectomy on the H3-leucine incorporation into the neurons of the premammillary and the arcuate nuclei, without changing the difference between the experiment and control in the macrocellular nuclei. On the whole, the results obtained permit a conclusion to be drawn on tonic inhibition by the epiphysis of the extensive hypothalamic zones.", "contents": "[The relationship between the pineal gland and the hypothalamo-hypophyseal complex. I. The effect of pinealectomy, binding and continuous illumination on H3-leucine incorporation in the nucleus of the anterior, middle and posterior hypothalamus of prepubertal and sexually mature rats]. Autoradiography was applied to the study of the effect of extirpation of the epiphysis in rats on the level of H3-leucine incorporation by the neurons of 8 couples of the nuclei localized in the anterior, middle and posterior portions of the hypothalamus. Experiments were conducted on female animals of the prepubertal and reproductive age. Pinealectomy was combined with binding (a factor intensifying the physiological status of the epiphysis) and continuous illumination (a factor inhibiting the function of this gland). In the blinded prepubertal rats pinealectomy enhanced the H3-leucine incorporation into the supraoptic nucleus by 38%, into the paraventricular--by 26%, into the dorsomedial--by 61%, into the premammillary dorsal--by 58%, into the ventro-medial--by 40%, into the premammillary ventral--by 36%, and into the anterior hypothalamic--by 26%. In mature rats this index exceeded, after pinealectomy, such in the sham-operated animals (control) in the supraoptic nucleus by 48%, in the paraventral--by 40%, in the premamillary ventral--by 80%, in the arcuate--by 48%, in the premammillary dorsal--by 35%, in the ventro-medial--by 29%, and in the dorso-medial--by 26%. Continuous illumination reduced the stimulating influence of pinealectomy on the H3-leucine incorporation into the neurons of the premammillary and the arcuate nuclei, without changing the difference between the experiment and control in the macrocellular nuclei. On the whole, the results obtained permit a conclusion to be drawn on tonic inhibition by the epiphysis of the extensive hypothalamic zones."} {"id": "PMID:1257214", "title": "[Surgical tactics for sex correction of patients with testicular forms of hermaphroditism].", "content": "On the basis of own material (43 patients) the author presents surgical tactics towards the testes in patients with testicular forms of hermaphroditism depending on the form of the disease. The authors consider that in the syndrome of dysgenesia of the testes the latter should be removed from the abdominal cavity (oncological danger!): when female sex is chosen--castration, and male--fixation of the testes under abdominal skin is indicated. In case of the syndrome of testicular feminization the testicles should be fixated under the abdominal skin by the authors' method. In case of the syndrome of incomplete masculinization (eunichoid form) the tactics is the same as in testicular feminization; in android form the testicles can be placed into the scrotum. Biopsy of the testes is necessary in all forms of hermaphroditism.", "contents": "[Surgical tactics for sex correction of patients with testicular forms of hermaphroditism]. On the basis of own material (43 patients) the author presents surgical tactics towards the testes in patients with testicular forms of hermaphroditism depending on the form of the disease. The authors consider that in the syndrome of dysgenesia of the testes the latter should be removed from the abdominal cavity (oncological danger!): when female sex is chosen--castration, and male--fixation of the testes under abdominal skin is indicated. In case of the syndrome of testicular feminization the testicles should be fixated under the abdominal skin by the authors' method. In case of the syndrome of incomplete masculinization (eunichoid form) the tactics is the same as in testicular feminization; in android form the testicles can be placed into the scrotum. Biopsy of the testes is necessary in all forms of hermaphroditism."} {"id": "PMID:1257222", "title": "[The calorigenic effect of catecholamines in rats with experimental hyper- and hypothyroidism].", "content": "RQ dynamics in rats, depending on the degree of organism's saturation with hormones, and also after catecholamine injection, was studied. Animals with a relatively mild hyperthyroidism had an increased RG as compared with control. RQ was decreased in the animals with a high degree of hyperthyroidism. Adrenaline and noradrenaline injection was accompanied by a decrease of RQ in the former case, and no changes in the latter case. Even relatively low triiodthyronin doses were shown to intensify the calorigenic catecholamine action. Reserpin injection produced no effect on the metabolic rate of hyperthyroid animals.", "contents": "[The calorigenic effect of catecholamines in rats with experimental hyper- and hypothyroidism]. RQ dynamics in rats, depending on the degree of organism's saturation with hormones, and also after catecholamine injection, was studied. Animals with a relatively mild hyperthyroidism had an increased RG as compared with control. RQ was decreased in the animals with a high degree of hyperthyroidism. Adrenaline and noradrenaline injection was accompanied by a decrease of RQ in the former case, and no changes in the latter case. Even relatively low triiodthyronin doses were shown to intensify the calorigenic catecholamine action. Reserpin injection produced no effect on the metabolic rate of hyperthyroid animals."} {"id": "PMID:1257223", "title": "[The effect of thyroid hormones on changes in the haptoglobin and transferrin levels in rats].", "content": "The author presents data concerning the experimental parallel study on male albino rats (171) of the effect of various thyroid hormones on the haptoglobin and transferrin level in the blood serum. On the basis of the data obtained a study was made of the correlation between the changes in the content of iodine-bound protein (IBP) and the mentioned blood glycoproteins in the experimental animals. There was revealed an influence of the thyroid gland on the content and the character of the changes in the haptoglobin and transferrin concentration in the blood serum. Within the range of physiological action thyroid hormones increased the level of blood component data, and in toxic doses--decreased it. The changes in the content of blood glycoproteins depended on the hormone, dosage and the duration of its administration. Between the changes in the concentration of IBP, haptoglobin and transferrin there proved to be a correlation in all the experimental groups with L-thyroxin and triiodthyronin toxicosis. Normalization of the haptoglobin and transferrin level occurred in the majority of the hyperthyroid animals 12 to 24 days after the end of the experiment.", "contents": "[The effect of thyroid hormones on changes in the haptoglobin and transferrin levels in rats]. The author presents data concerning the experimental parallel study on male albino rats (171) of the effect of various thyroid hormones on the haptoglobin and transferrin level in the blood serum. On the basis of the data obtained a study was made of the correlation between the changes in the content of iodine-bound protein (IBP) and the mentioned blood glycoproteins in the experimental animals. There was revealed an influence of the thyroid gland on the content and the character of the changes in the haptoglobin and transferrin concentration in the blood serum. Within the range of physiological action thyroid hormones increased the level of blood component data, and in toxic doses--decreased it. The changes in the content of blood glycoproteins depended on the hormone, dosage and the duration of its administration. Between the changes in the concentration of IBP, haptoglobin and transferrin there proved to be a correlation in all the experimental groups with L-thyroxin and triiodthyronin toxicosis. Normalization of the haptoglobin and transferrin level occurred in the majority of the hyperthyroid animals 12 to 24 days after the end of the experiment."} {"id": "PMID:1257224", "title": "[The effect of chlorpropamide on the course of latent insular insufficiency in rats under conditions favorable for its transition to patent diabetes].", "content": "Experiments were conducted on 162 female rats which had sustained alloxan diabetes during the period of sexual immaturity and had latent insular insufficiency (prediabetes and latent diabetes). Possibilities of chlorpropamide under conditions promoting decompensation development were studied. The animals were given propamide in daily doses of 100 mg per 1 kg of weight for one month, including the period of sexual maturation. Observation period--up to 5 months. A favourable effect of chlorpropamide was noted by the end of puberty and persisted in the course of further observation; the difference from control animals by the frequency of latent and manifest diabetes was intensified under the effect of glucose overfeeding during the perinatal period. Chlorpropamide improved the course of latent insular insufficiency in the rats and was capable of preventing its change into manifest diabetes.", "contents": "[The effect of chlorpropamide on the course of latent insular insufficiency in rats under conditions favorable for its transition to patent diabetes]. Experiments were conducted on 162 female rats which had sustained alloxan diabetes during the period of sexual immaturity and had latent insular insufficiency (prediabetes and latent diabetes). Possibilities of chlorpropamide under conditions promoting decompensation development were studied. The animals were given propamide in daily doses of 100 mg per 1 kg of weight for one month, including the period of sexual maturation. Observation period--up to 5 months. A favourable effect of chlorpropamide was noted by the end of puberty and persisted in the course of further observation; the difference from control animals by the frequency of latent and manifest diabetes was intensified under the effect of glucose overfeeding during the perinatal period. Chlorpropamide improved the course of latent insular insufficiency in the rats and was capable of preventing its change into manifest diabetes."} {"id": "PMID:1257219", "title": "[The activity of the dehydrogenases of the tricarboxylic acid cycle and concentration of adenylic nucleotides in the brain and liver in experimental hypothyroidism].", "content": "A determination was made of the activity of the cycle of tricarbolic acids of dehydrogenases and of the content of adeninnucleotides in the brain and the liver of rats in experimental hypothyroidism caused by mercasolyl administration. There were revealed deviations in the activity of dehydrogenases, more pronounced in the liver. Adeninnucleotide content was found to be reduced only in the brain. ATP/ADP ratio decreased in both tissues. The data obtained are discussed with consideration to the possibility of allosteric regulation of the enzyme activity and peculiarities attending the metabolism of substances in the tissues under study.", "contents": "[The activity of the dehydrogenases of the tricarboxylic acid cycle and concentration of adenylic nucleotides in the brain and liver in experimental hypothyroidism]. A determination was made of the activity of the cycle of tricarbolic acids of dehydrogenases and of the content of adeninnucleotides in the brain and the liver of rats in experimental hypothyroidism caused by mercasolyl administration. There were revealed deviations in the activity of dehydrogenases, more pronounced in the liver. Adeninnucleotide content was found to be reduced only in the brain. ATP/ADP ratio decreased in both tissues. The data obtained are discussed with consideration to the possibility of allosteric regulation of the enzyme activity and peculiarities attending the metabolism of substances in the tissues under study."} {"id": "PMID:1257218", "title": "[The role of noradrenaline in regulating the thyrotropic function of the hypophysis].", "content": "Acute experiments were conducted on male rats; a study was made of the effect of microinjections of noradrenaline into the hypothalamus on the thyrotropic function of the hypophysis. Administration of the mediator into the anterior part of the medio-basal hypothalamus led to reduction of the level of thyrotropic hormone in the blood serum and its accumulation in the hypophysis in determination by radioimmunological method. Noradrenaline injections into the area of the paraventricular nucleus practically did not alter the thyrotropic function of the hypophysis.", "contents": "[The role of noradrenaline in regulating the thyrotropic function of the hypophysis]. Acute experiments were conducted on male rats; a study was made of the effect of microinjections of noradrenaline into the hypothalamus on the thyrotropic function of the hypophysis. Administration of the mediator into the anterior part of the medio-basal hypothalamus led to reduction of the level of thyrotropic hormone in the blood serum and its accumulation in the hypophysis in determination by radioimmunological method. Noradrenaline injections into the area of the paraventricular nucleus practically did not alter the thyrotropic function of the hypophysis."} {"id": "PMID:1257220", "title": "[The effect of insulin on amino acid accumulation and their incorporation into the proteins of incubated rat diaphragm. The effect of preliminary hypophysectomy and experimental diabetes].", "content": "A study was made of the effect of insulin on some indices of protein metabolism in the incubated muscle of the diaphragm obtained from intact rats, hypophysectomized animals, rats with alloxan diabetes and animals with a combined functional exclusion of the hypophysis and the pancreas. Preliminary hypophysectomy depressed and alloxan diabetes increased the effect of insulin on leucin-C14 incorporation into the protein of the diaphragm. At the same time both preliminary actions promoted an increase of sensitivity of the incubated diaphragm to insulin as seen in examination of accumulation of H3-alphaaminoisobutyric acid. Combined exclusion of the function of the hypophysis and the pancreas led to less pronounced changes in the sensitivity of the diaphragm to insulin than each of the actions separately.", "contents": "[The effect of insulin on amino acid accumulation and their incorporation into the proteins of incubated rat diaphragm. The effect of preliminary hypophysectomy and experimental diabetes]. A study was made of the effect of insulin on some indices of protein metabolism in the incubated muscle of the diaphragm obtained from intact rats, hypophysectomized animals, rats with alloxan diabetes and animals with a combined functional exclusion of the hypophysis and the pancreas. Preliminary hypophysectomy depressed and alloxan diabetes increased the effect of insulin on leucin-C14 incorporation into the protein of the diaphragm. At the same time both preliminary actions promoted an increase of sensitivity of the incubated diaphragm to insulin as seen in examination of accumulation of H3-alphaaminoisobutyric acid. Combined exclusion of the function of the hypophysis and the pancreas led to less pronounced changes in the sensitivity of the diaphragm to insulin than each of the actions separately."} {"id": "PMID:1257227", "title": "[The rate of cortisol secretion in patients with diabetes mellitus].", "content": "Velocity of cortizol secretion (VCS) was studied in 5 healthy individuals and 30 patients with diabetes mellitus by the method of dilution of the isotopic label by the mean specific radioactivity of tetrahydrocortizol and tetrahydrocortisone excreted with the urine. There was revealed a close interrelationship between the activation of the adrenal glands and the extent of decompensation of the disease: during the subcompensation and compensation the VCS of the patients with normal weight was no different from the normal and during the decompensation--increased in the majority of the patients investigated; this elevation was more pronounced in marked glucoseuria. The duration of the disease produced no significant influence on the secretory capacity of the adrenal glands.", "contents": "[The rate of cortisol secretion in patients with diabetes mellitus]. Velocity of cortizol secretion (VCS) was studied in 5 healthy individuals and 30 patients with diabetes mellitus by the method of dilution of the isotopic label by the mean specific radioactivity of tetrahydrocortizol and tetrahydrocortisone excreted with the urine. There was revealed a close interrelationship between the activation of the adrenal glands and the extent of decompensation of the disease: during the subcompensation and compensation the VCS of the patients with normal weight was no different from the normal and during the decompensation--increased in the majority of the patients investigated; this elevation was more pronounced in marked glucoseuria. The duration of the disease produced no significant influence on the secretory capacity of the adrenal glands."} {"id": "PMID:1257226", "title": "[Adipose tissue sensitivity to insulin in obese ovariectomized rats].", "content": "A study was made of sensitivity of the isolated adipose tissue in rats with ovariectomy and overfeeding. Insulin sensitivity was assessed by the intensity of glucose-C14 incorporation into total lipids of adipose tissue in its incubation with insulin in a concentration of 100 minutes/ml. It was demonstrated that 3 1/2 months after the operation no adiposity developed in ovariectomized rats and insulin sensitivity of the adipose tissue persisted at the normal level. In the excessively fed animals, which due to individual peculiarities of food consumption retained their normal weight, insulin sensitivity of the adipose tissue also remained unchanged. At the same time, with increase in weight caused by overfeeding or ovariectomy in combination with overfeeding, there was no intensification of glucose metabolism under the effect of insulin. The mentioned reduction of insulin sensitivity apparently served as one of the causes leading to development of a relative insulin insufficiency in adiposity and the subsequent development of disturbances of carbohydrate and fat metabolism.", "contents": "[Adipose tissue sensitivity to insulin in obese ovariectomized rats]. A study was made of sensitivity of the isolated adipose tissue in rats with ovariectomy and overfeeding. Insulin sensitivity was assessed by the intensity of glucose-C14 incorporation into total lipids of adipose tissue in its incubation with insulin in a concentration of 100 minutes/ml. It was demonstrated that 3 1/2 months after the operation no adiposity developed in ovariectomized rats and insulin sensitivity of the adipose tissue persisted at the normal level. In the excessively fed animals, which due to individual peculiarities of food consumption retained their normal weight, insulin sensitivity of the adipose tissue also remained unchanged. At the same time, with increase in weight caused by overfeeding or ovariectomy in combination with overfeeding, there was no intensification of glucose metabolism under the effect of insulin. The mentioned reduction of insulin sensitivity apparently served as one of the causes leading to development of a relative insulin insufficiency in adiposity and the subsequent development of disturbances of carbohydrate and fat metabolism."} {"id": "PMID:1257243", "title": "Influence of ketamine, phenylcyclidine, and phenobarbital on cholesterol metabolism in rats.", "content": "The effects of ip injections of phenobarbital (100 mg/kg), phenylcyclidine (Sernylan; [1-(1-phenylcyclohexyl)-piperidine-HBl] (1 mg/kg), and ketamine (Ketaset; [dl)2-O-chlorophenyl)-2-(methylamino)cyclohexanone-HCl] (1 mg/kg) on lipid metabolism in rats were compared. This study was undertaken to determine whether the two sedatives currently used in primates share any of the undesirable effects of phenobarbital on lipid metabolism. All three compounds were administered to male Wistar rats for 6 days. Phenobarbital was hepatomegalic, stimulated 7alpha hydroxylation of cholesterol, and inhibited cholesterol synthesis by rat liver slices from mevalonate, but not acetate. The two other sedatives exhibited effects very similar to those observed in the controls. From our work in rats it is concluded that the use of Sernylan or Ketaset for sedation of nonhuman primates will not significantly affect these parameters of lipid metabolism.", "contents": "Influence of ketamine, phenylcyclidine, and phenobarbital on cholesterol metabolism in rats. The effects of ip injections of phenobarbital (100 mg/kg), phenylcyclidine (Sernylan; [1-(1-phenylcyclohexyl)-piperidine-HBl] (1 mg/kg), and ketamine (Ketaset; [dl)2-O-chlorophenyl)-2-(methylamino)cyclohexanone-HCl] (1 mg/kg) on lipid metabolism in rats were compared. This study was undertaken to determine whether the two sedatives currently used in primates share any of the undesirable effects of phenobarbital on lipid metabolism. All three compounds were administered to male Wistar rats for 6 days. Phenobarbital was hepatomegalic, stimulated 7alpha hydroxylation of cholesterol, and inhibited cholesterol synthesis by rat liver slices from mevalonate, but not acetate. The two other sedatives exhibited effects very similar to those observed in the controls. From our work in rats it is concluded that the use of Sernylan or Ketaset for sedation of nonhuman primates will not significantly affect these parameters of lipid metabolism."} {"id": "PMID:1257244", "title": "Effect of methyldopa treatment on cardiac function and myocardial blood flow in mongrel dogs.", "content": "Administration of methyldopa (100 mg/kg, orally twice daily for a period of 3 days) to mongrel dogs produced significant reductions in blood pressure and heart rate. The hypotensive effect of the drug was due to a reduction in peripheral resistance. Methyldopa treatment also produced a significant decrease in coronary vascular resistance. Studies on the left ventricular function indicated that treatment with methyldopa does not compromise the ability of the myocardium to respond to an increased work load. Thus, the beneficial effect of this agent on the myocardial circulation, together with its lack of any detrimental effect on the cardiac function suggest that methyldopa may be an effective agent for the control of hypertension.", "contents": "Effect of methyldopa treatment on cardiac function and myocardial blood flow in mongrel dogs. Administration of methyldopa (100 mg/kg, orally twice daily for a period of 3 days) to mongrel dogs produced significant reductions in blood pressure and heart rate. The hypotensive effect of the drug was due to a reduction in peripheral resistance. Methyldopa treatment also produced a significant decrease in coronary vascular resistance. Studies on the left ventricular function indicated that treatment with methyldopa does not compromise the ability of the myocardium to respond to an increased work load. Thus, the beneficial effect of this agent on the myocardial circulation, together with its lack of any detrimental effect on the cardiac function suggest that methyldopa may be an effective agent for the control of hypertension."} {"id": "PMID:1257245", "title": "Effects of sodium intake on renal cortical blood flow distribution.", "content": "Renal cortical blood flow and superficial cortical blood flow were measured in chronic sodium-loaded, sodium-deprived and normal rats. Neither total renal cortical blood flow was different among the three groups of animals. Alterations in the amount of sodium excreted, therefore, are not related to alterations of renal cortical blood flow distribution.", "contents": "Effects of sodium intake on renal cortical blood flow distribution. Renal cortical blood flow and superficial cortical blood flow were measured in chronic sodium-loaded, sodium-deprived and normal rats. Neither total renal cortical blood flow was different among the three groups of animals. Alterations in the amount of sodium excreted, therefore, are not related to alterations of renal cortical blood flow distribution."} {"id": "PMID:1257246", "title": "Contractile responses to epinephrine, serotonin, and potassium in arterial smooth muscle.", "content": "Effects of epinephrine, serotonin, and KCl on development of isometric tension were studied in strips of rat femoral and tail artery smooth muscle. Strkining differences were detected between the preparations. Tension development in tail artery smooth muscle was greatest with epinephrine, intermediate with serotonin, and least with K+. In femoral preparations tension developed was greatest with serotonin. Smaller but comparable contractions were elicited with epinephrine and K+. Theoretical and experimental dose-response curves for epinephrine and serotonin agreed closely, whereas curves for K+ differed markedly. The relationship between fractional response and fractional stimulus was hyperbolic for epinephrine and serotonin but sigmoid for K+. The Hill coefficient for serotonin was about 1, slightly smaller than 1 for epinephrine (0.5 to 0.8) and significantly greater for K+ (5 to 5). These findings show that responses elicited with either epinephrine or serotonin are mechanistically consistent with receptor occupancy theory. They suggest that specific receptors for K+ exist and that they may involve positive cooperative interactions similar those described for receptor mechanisms in electroplax.", "contents": "Contractile responses to epinephrine, serotonin, and potassium in arterial smooth muscle. Effects of epinephrine, serotonin, and KCl on development of isometric tension were studied in strips of rat femoral and tail artery smooth muscle. Strkining differences were detected between the preparations. Tension development in tail artery smooth muscle was greatest with epinephrine, intermediate with serotonin, and least with K+. In femoral preparations tension developed was greatest with serotonin. Smaller but comparable contractions were elicited with epinephrine and K+. Theoretical and experimental dose-response curves for epinephrine and serotonin agreed closely, whereas curves for K+ differed markedly. The relationship between fractional response and fractional stimulus was hyperbolic for epinephrine and serotonin but sigmoid for K+. The Hill coefficient for serotonin was about 1, slightly smaller than 1 for epinephrine (0.5 to 0.8) and significantly greater for K+ (5 to 5). These findings show that responses elicited with either epinephrine or serotonin are mechanistically consistent with receptor occupancy theory. They suggest that specific receptors for K+ exist and that they may involve positive cooperative interactions similar those described for receptor mechanisms in electroplax."} {"id": "PMID:1257247", "title": "Microvibration: capable of inducing spontaneous contractions in smooth muscles.", "content": "Spontaneous contractions were elicited by the vibration of small amplitude (microvibration) imposed upon the quiescent strips prepared from the ureter and portal vein of dogs. An acceleration of the existing rhythm in the spontaneously contracting strips was also brought about by microvibration. Frequencies and amplitudes of microvibration ranged from 1 to 90 Hz and from 50 to 150 mum, respectively. Imposed cyclic strains were less than 1% at their maximum. Up to the amplitude of 150 mum, the greater the amplitude, the faster the induced rhythm. Stepwise increase of the frequencies up to 30 Hz brought about a gradual acceleration of rhythmicity. At frequencies of above 30 Hz, no appreciable frequency-dependent differences were observable among the responses induced. Local adrenergic mechanism proved to have nothing to do with these effects.", "contents": "Microvibration: capable of inducing spontaneous contractions in smooth muscles. Spontaneous contractions were elicited by the vibration of small amplitude (microvibration) imposed upon the quiescent strips prepared from the ureter and portal vein of dogs. An acceleration of the existing rhythm in the spontaneously contracting strips was also brought about by microvibration. Frequencies and amplitudes of microvibration ranged from 1 to 90 Hz and from 50 to 150 mum, respectively. Imposed cyclic strains were less than 1% at their maximum. Up to the amplitude of 150 mum, the greater the amplitude, the faster the induced rhythm. Stepwise increase of the frequencies up to 30 Hz brought about a gradual acceleration of rhythmicity. At frequencies of above 30 Hz, no appreciable frequency-dependent differences were observable among the responses induced. Local adrenergic mechanism proved to have nothing to do with these effects."} {"id": "PMID:1257248", "title": "Effect of cytosine, arabinoside, iododeoxyuridine, ethyldeoxyuridine, thiocyanatodeoxyuridine, and ribavirin on tail lesion formation in mice infected with vaccinia virus.", "content": "Mice infected intravenously with vaccinia virus develop characteristic lesions over the entire tail surface. This experimental virus infection presents a highly sensitive and reliable model for evaluating the antivaccinia activity of antiviral compounds. Ara-C (1-beta-D-arabinofuranosylcytosine), ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), IUdR (5-iodo-2'-deoxyuridine) as well as two novel analogs of IUdR, EtUdR (5-ethyl-2'-deoxyuridine), and NCSUdR (5-thiocyanato-2'-deoxyuridine), were found to inhibit the formation of vaccinia tail lesions, when administered intraperitoneally once daily for 7 days starting immediately after virus infection. The order of (decreasing) activity was: ara-C greater than IUdR greater than NCSUdR greater than ribavirin greater than EtUdR. Various drug combinations, involving IUdR + ara-C, NCSUdR + ara-C, NCSUdR + IUdR, NSCUdR + ribavirin, etc., were evaluated but none proved more efficacious than either compound administered alone.", "contents": "Effect of cytosine, arabinoside, iododeoxyuridine, ethyldeoxyuridine, thiocyanatodeoxyuridine, and ribavirin on tail lesion formation in mice infected with vaccinia virus. Mice infected intravenously with vaccinia virus develop characteristic lesions over the entire tail surface. This experimental virus infection presents a highly sensitive and reliable model for evaluating the antivaccinia activity of antiviral compounds. Ara-C (1-beta-D-arabinofuranosylcytosine), ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide), IUdR (5-iodo-2'-deoxyuridine) as well as two novel analogs of IUdR, EtUdR (5-ethyl-2'-deoxyuridine), and NCSUdR (5-thiocyanato-2'-deoxyuridine), were found to inhibit the formation of vaccinia tail lesions, when administered intraperitoneally once daily for 7 days starting immediately after virus infection. The order of (decreasing) activity was: ara-C greater than IUdR greater than NCSUdR greater than ribavirin greater than EtUdR. Various drug combinations, involving IUdR + ara-C, NCSUdR + ara-C, NCSUdR + IUdR, NSCUdR + ribavirin, etc., were evaluated but none proved more efficacious than either compound administered alone."} {"id": "PMID:1257249", "title": "Enhanced erythropoietin and prostaglandin E production in the dog following renal artery constriction.", "content": "Renal artery constriction (RAC) to 30% of normal flow for 12 hr in the unilaterally nephrectomized dog produced a marked increase in both erythropoietin titers and prostaglandin E (PGE) levels in the blood. In dogs pretreated prior to RAC with indomethacin, a potent inhibitor of prostaglandin synthetase, there was no significant increase in either PGE or erythropoietin levels as compared to zero-time control values. These data suggested an involvement of renal PGE in the generation of erythropoietin following RAC.", "contents": "Enhanced erythropoietin and prostaglandin E production in the dog following renal artery constriction. Renal artery constriction (RAC) to 30% of normal flow for 12 hr in the unilaterally nephrectomized dog produced a marked increase in both erythropoietin titers and prostaglandin E (PGE) levels in the blood. In dogs pretreated prior to RAC with indomethacin, a potent inhibitor of prostaglandin synthetase, there was no significant increase in either PGE or erythropoietin levels as compared to zero-time control values. These data suggested an involvement of renal PGE in the generation of erythropoietin following RAC."} {"id": "PMID:1257250", "title": "Melatonin-induced inhibition of testicular function in adult golden hamsters.", "content": "Melatonin (12-100 mug/day) administered via subcutaneous Silastic implants prevented or suppressed light-induced testicular recrudescence in adult golden hamsters. In addition, melatonin (150 mug/day) induced marked testicular regression in sexually mature hamsters maintained on photostimulatory long days. These results clearly establish that exogenous melatonin can inhibit gonodal function in adult male hamsters.", "contents": "Melatonin-induced inhibition of testicular function in adult golden hamsters. Melatonin (12-100 mug/day) administered via subcutaneous Silastic implants prevented or suppressed light-induced testicular recrudescence in adult golden hamsters. In addition, melatonin (150 mug/day) induced marked testicular regression in sexually mature hamsters maintained on photostimulatory long days. These results clearly establish that exogenous melatonin can inhibit gonodal function in adult male hamsters."} {"id": "PMID:1257251", "title": "Effects of aging on LH and prolactin after LHRL L-dopa, methyl-dopa, and stress in male rat.", "content": "Hypothalamic-pituitary control of prolactin and LH secretion was tested in young (4-6 months) and aged (22-30 months) male Long-Evans rats given L-dopa, methyl dopa, LHRH, or stress treatments. Pretreatment serum LH levels were consistently higher in young than in the aged groups. The increase in serum LH after LHRH injection was only about half as much in aged as compared to young control males. Although acute stress caused a prompt increase in serum LH in young male rats, this treatment was without effect in the aged group. Methyl dopa treatment stimulated serum prolactin secretion in both young and old rats. Although L-dopa treatment caused a reduction in serum prolactin in both age groups, the sensitivity, magnitude, and duration of the reduction was smaller in the aged rats.", "contents": "Effects of aging on LH and prolactin after LHRL L-dopa, methyl-dopa, and stress in male rat. Hypothalamic-pituitary control of prolactin and LH secretion was tested in young (4-6 months) and aged (22-30 months) male Long-Evans rats given L-dopa, methyl dopa, LHRH, or stress treatments. Pretreatment serum LH levels were consistently higher in young than in the aged groups. The increase in serum LH after LHRH injection was only about half as much in aged as compared to young control males. Although acute stress caused a prompt increase in serum LH in young male rats, this treatment was without effect in the aged group. Methyl dopa treatment stimulated serum prolactin secretion in both young and old rats. Although L-dopa treatment caused a reduction in serum prolactin in both age groups, the sensitivity, magnitude, and duration of the reduction was smaller in the aged rats."} {"id": "PMID:1257252", "title": "Modification of the hepatotoxicity of D-galactosamine in the rat by cycloheximide.", "content": "The effect of cycloheximide (1.5 mg/kg), a potent inhibitor of protein biosynthesis, on D-galastosamine (375 mg/kg)-induced hepatic necrosis and hepatic triglyceride accumulation was studied in rats. Serum transaminase levels, 24 hr after D-galactosamine administration, were significantly reduced in animals treated simultaneously or 4 hr before D-galactosamine with cycloheximide, when compared to animals given D-galactosamine alone. Transaminase levels in rats given cycloheximide 4 hr after D-galactosamine were not reduced. Histological grading of hepatocyte necrosis showed a similar pattern of protection in the pretreated and simultaneously treated groups. Hepatic triglycerides were significantly reduced only in the latter group. Fatality 48 hr after D-galactosamine administration was significantly less common in rats pretreated with cycloheximide when compared to rats given D-galactosamine without cycloheximide, and surviving animals in the cycloheximide pretreated group had a lower serum transaminase level, a lower necrosis score, and a reduced hepatic triglyceride level. These data are consistent with the concept that protein synthesis is important in the pathogenesis of D-galactosamine-induced hepatotoxicity.", "contents": "Modification of the hepatotoxicity of D-galactosamine in the rat by cycloheximide. The effect of cycloheximide (1.5 mg/kg), a potent inhibitor of protein biosynthesis, on D-galastosamine (375 mg/kg)-induced hepatic necrosis and hepatic triglyceride accumulation was studied in rats. Serum transaminase levels, 24 hr after D-galactosamine administration, were significantly reduced in animals treated simultaneously or 4 hr before D-galactosamine with cycloheximide, when compared to animals given D-galactosamine alone. Transaminase levels in rats given cycloheximide 4 hr after D-galactosamine were not reduced. Histological grading of hepatocyte necrosis showed a similar pattern of protection in the pretreated and simultaneously treated groups. Hepatic triglycerides were significantly reduced only in the latter group. Fatality 48 hr after D-galactosamine administration was significantly less common in rats pretreated with cycloheximide when compared to rats given D-galactosamine without cycloheximide, and surviving animals in the cycloheximide pretreated group had a lower serum transaminase level, a lower necrosis score, and a reduced hepatic triglyceride level. These data are consistent with the concept that protein synthesis is important in the pathogenesis of D-galactosamine-induced hepatotoxicity."} {"id": "PMID:1257253", "title": "Cytotoxic effects of 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) on cultured human glioblastomas.", "content": "Two cultured human glioblastoma cell lines were exposed to graded doses of BCNU, and the sequential cytoxic and cytocidal changes were studied histologically. Changes included cessation of mitotic activity, reduction in population, rounding and clumping of the cells, nuclear pyknosis, and cell death. The intensity of the changes was proportional to the dosage. With 3 daily doses of 18 mug/ml, the population in Tumor A-172 was only 20% of that in the controls, and 75% of the cells present appeared conviable. This dosage is about four times that used in a single course in treating humans. After 3 doses at 60 mug/ml, cell death appeared complete, but transfer without additional treatment brought out 2-min foci of viable cells, with several mitoses. A more anaplastic glioblastoma, T98, was much less sensitive to BCNU, responding only by lowered population density, decreased mitoses and slight-to-moderate cytotoxicity in one experiment.", "contents": "Cytotoxic effects of 1,3-bis(2 chloroethyl)-1-nitrosourea (BCNU) on cultured human glioblastomas. Two cultured human glioblastoma cell lines were exposed to graded doses of BCNU, and the sequential cytoxic and cytocidal changes were studied histologically. Changes included cessation of mitotic activity, reduction in population, rounding and clumping of the cells, nuclear pyknosis, and cell death. The intensity of the changes was proportional to the dosage. With 3 daily doses of 18 mug/ml, the population in Tumor A-172 was only 20% of that in the controls, and 75% of the cells present appeared conviable. This dosage is about four times that used in a single course in treating humans. After 3 doses at 60 mug/ml, cell death appeared complete, but transfer without additional treatment brought out 2-min foci of viable cells, with several mitoses. A more anaplastic glioblastoma, T98, was much less sensitive to BCNU, responding only by lowered population density, decreased mitoses and slight-to-moderate cytotoxicity in one experiment."} {"id": "PMID:1257254", "title": "Inhibitory effects of scillaren and dinitrophenol on bilirubin excretion by the isolated perfused rat liver.", "content": "The effects of scillaren and dinitrophenol on bilirubin excretion by the perfused rat liver were studied. Both compounds inhibited bile flow, scillaren by 20 to 40%, and dinitrophenol by 60 to 80%. Bilirubin excretion was also impaired. However, the effect of scillaren on bilirubin excretion was less than that on bile flow, as indicated by an increase in the bile bilirubin concentration, whereas dinitrophenol had a greater effect on bilirubin excretion than on bile flow. Dinitrophenol also inhibited the hepatic removal of unconjugated bilirubin from the perfusate, probably because it impaired the initial uptake and/or storage of unconjugated bilirubin by the perfused liver.", "contents": "Inhibitory effects of scillaren and dinitrophenol on bilirubin excretion by the isolated perfused rat liver. The effects of scillaren and dinitrophenol on bilirubin excretion by the perfused rat liver were studied. Both compounds inhibited bile flow, scillaren by 20 to 40%, and dinitrophenol by 60 to 80%. Bilirubin excretion was also impaired. However, the effect of scillaren on bilirubin excretion was less than that on bile flow, as indicated by an increase in the bile bilirubin concentration, whereas dinitrophenol had a greater effect on bilirubin excretion than on bile flow. Dinitrophenol also inhibited the hepatic removal of unconjugated bilirubin from the perfusate, probably because it impaired the initial uptake and/or storage of unconjugated bilirubin by the perfused liver."} {"id": "PMID:1257255", "title": "Specificity of neural effect on renal tubular sodium reabsorption.", "content": "Low level direct renal nerve stimulation increases renal tubular sodium reabsorption in the absence of changes in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. Blockade of this response with phenoxybenzamine (or guanethidine) supports the interpretation that it is mediated by direct adrenergic innervation of the renal tubule.", "contents": "Specificity of neural effect on renal tubular sodium reabsorption. Low level direct renal nerve stimulation increases renal tubular sodium reabsorption in the absence of changes in glomerular filtration rate, renal blood flow, or intrarenal distribution of blood flow. Blockade of this response with phenoxybenzamine (or guanethidine) supports the interpretation that it is mediated by direct adrenergic innervation of the renal tubule."} {"id": "PMID:1257256", "title": "Influence of antidiuretic hormone on intrarenal blood flow distribution in diabetes insipidus dogs and rats.", "content": "The distribution of labeled microspheres within the renal cortex was used to evaluate the influence of physiological amounts of antidiuretic hormone on intrarenal blood flow distribution in hypophysectomized dogs and in rats with hereditary diabetes insipidus. In both species, intravenous infusions of ADH caused a significant decrease in the ratio of inner to outer cortical blood flow. The change in blood flow distribution observed in the hypophysectomized dog with ADH was primarily a consequence of a decrease in inner cortical blood flow. No consistent changes in outer cortical blood flow were found. Also in the dog, glomerular filtration rates and electrolyte excretion rates (Na and K) increased following ADH. In contrast, ADH infusion into Brattleboro rats caused no change in glomerular filtration or excretion of Na and K.", "contents": "Influence of antidiuretic hormone on intrarenal blood flow distribution in diabetes insipidus dogs and rats. The distribution of labeled microspheres within the renal cortex was used to evaluate the influence of physiological amounts of antidiuretic hormone on intrarenal blood flow distribution in hypophysectomized dogs and in rats with hereditary diabetes insipidus. In both species, intravenous infusions of ADH caused a significant decrease in the ratio of inner to outer cortical blood flow. The change in blood flow distribution observed in the hypophysectomized dog with ADH was primarily a consequence of a decrease in inner cortical blood flow. No consistent changes in outer cortical blood flow were found. Also in the dog, glomerular filtration rates and electrolyte excretion rates (Na and K) increased following ADH. In contrast, ADH infusion into Brattleboro rats caused no change in glomerular filtration or excretion of Na and K."} {"id": "PMID:1257257", "title": "Secretion of human prolactin in vitro.", "content": "Cells from two human pituitary tumors were grown in capillary culture units and prolactin production was measured. A single unit could produce 3 mg of prolactin over a 4-month period. The cultured cells responded to TRH exposure by increasing their rate of prolactin secretion. Cultivation of cells in capillary units could be the method of choice for reducing the shortage of human hormones.", "contents": "Secretion of human prolactin in vitro. Cells from two human pituitary tumors were grown in capillary culture units and prolactin production was measured. A single unit could produce 3 mg of prolactin over a 4-month period. The cultured cells responded to TRH exposure by increasing their rate of prolactin secretion. Cultivation of cells in capillary units could be the method of choice for reducing the shortage of human hormones."} {"id": "PMID:1257258", "title": "Mercury in human maternal and cord blood, placenta, and milk.", "content": "Total mercury concentration was measured by atomic absorption spectrophotometry in 100 maternal-umbilical cord blood pairs, 39 placentae, and 32 breast milk samples, all from patients at the University of Iowa Hospitals. The mean maternal and cord blood levels were 1.01 and 1.24 parts per billion (ppb), respectively. Though the difference between maternal and cord values was not statistically significant, the two were significantly correlated with each other, and maternal blood level increased significantly with maternal age. Mean placental and milk concentrations were 2.28 and 0.93 ppb, respectively. The mercury levels in this study were lower than those reported from elsewhere, probably reflecting a combination of methodological refinement and relatively low mercury exposure in a rural population whose diet is low in fish consumption. These low levels suggest that the risk of perinatal mercury damage is small in such a population.", "contents": "Mercury in human maternal and cord blood, placenta, and milk. Total mercury concentration was measured by atomic absorption spectrophotometry in 100 maternal-umbilical cord blood pairs, 39 placentae, and 32 breast milk samples, all from patients at the University of Iowa Hospitals. The mean maternal and cord blood levels were 1.01 and 1.24 parts per billion (ppb), respectively. Though the difference between maternal and cord values was not statistically significant, the two were significantly correlated with each other, and maternal blood level increased significantly with maternal age. Mean placental and milk concentrations were 2.28 and 0.93 ppb, respectively. The mercury levels in this study were lower than those reported from elsewhere, probably reflecting a combination of methodological refinement and relatively low mercury exposure in a rural population whose diet is low in fish consumption. These low levels suggest that the risk of perinatal mercury damage is small in such a population."} {"id": "PMID:1257259", "title": "Studies on the isolation and chemical properties of porcine follicle-stimulating hormone.", "content": "Porcine follicle-stimulating hormone (pFSH) has been prepared from acetone dried pituitary glands. The acetone powder was initially extracted in pH 5 ethanol-acetate buffer (40% ethanol and acetate at 0.5 ionic strength) containing 0.02% PMSF. The gonadotropin rich fraction, obtained in the 80% ethanol precipitate, was dissolved in 0.12 M NH4HCO3, heated at 60 degrees for 3 min, cooled, and centrifuged. The supernatant was lyophilized for chromatography on QAE-Sephadex, then Sephadex G-100. The pFSH obtained has a biological activity of 15 X NIH-FSH-P-1 and 2.1% sialic acid. The amino acid analysis is characterized by high lysine, aspartic acid, and glutamic acid with notable amounts of threonine, proline, and half-cystine.", "contents": "Studies on the isolation and chemical properties of porcine follicle-stimulating hormone. Porcine follicle-stimulating hormone (pFSH) has been prepared from acetone dried pituitary glands. The acetone powder was initially extracted in pH 5 ethanol-acetate buffer (40% ethanol and acetate at 0.5 ionic strength) containing 0.02% PMSF. The gonadotropin rich fraction, obtained in the 80% ethanol precipitate, was dissolved in 0.12 M NH4HCO3, heated at 60 degrees for 3 min, cooled, and centrifuged. The supernatant was lyophilized for chromatography on QAE-Sephadex, then Sephadex G-100. The pFSH obtained has a biological activity of 15 X NIH-FSH-P-1 and 2.1% sialic acid. The amino acid analysis is characterized by high lysine, aspartic acid, and glutamic acid with notable amounts of threonine, proline, and half-cystine."} {"id": "PMID:1257260", "title": "Effect of vaginally administered 15(S)15-methyl-PGF2alpha on egg transport and fertility in rabbits.", "content": "The effects of vaginal suppositories containing 1.0 mg of 15[S]15-methy-PGF2alpha on oviductal motility, egg transport, and fertility were determined in rabbits. Suppository treatment caused a significant increase (P less than 0.02) in the amplitude of oviductal contractions, and a decrease in the frequency of contractractions (P less than 0.04). Altered oviductal motility persisted for an average of 2 hr after treatment. Treatment with 1, 2, or 3 suppositories at various times after ovulation caused a significant reduction in the number of eggs located in the oviducts (P less than 0.025). There was, however, a great deal of variation in egg recovery in treated animals (range 0 to 100%). Treatment of mated rabbits during the time of tubal egg transport caused a significant reduction in the number of Day-12 implants (P less than 0.05). The percentage of corpora lutea represented by Day-12 implants was similar to egg recovery rates in animals similarly treated. The treatment had no effect on fetal survival from Day 12 to 28 of pregnancy. The decrease in fertility caused by these vaginal suppositories is presumably due to the stimulatory effect on oviductal motility which accelerates tubal transport of the embryos into the uterus. Embryos that arrive in the uterus prematurely probably do not implant and degenerate or are expelled.", "contents": "Effect of vaginally administered 15(S)15-methyl-PGF2alpha on egg transport and fertility in rabbits. The effects of vaginal suppositories containing 1.0 mg of 15[S]15-methy-PGF2alpha on oviductal motility, egg transport, and fertility were determined in rabbits. Suppository treatment caused a significant increase (P less than 0.02) in the amplitude of oviductal contractions, and a decrease in the frequency of contractractions (P less than 0.04). Altered oviductal motility persisted for an average of 2 hr after treatment. Treatment with 1, 2, or 3 suppositories at various times after ovulation caused a significant reduction in the number of eggs located in the oviducts (P less than 0.025). There was, however, a great deal of variation in egg recovery in treated animals (range 0 to 100%). Treatment of mated rabbits during the time of tubal egg transport caused a significant reduction in the number of Day-12 implants (P less than 0.05). The percentage of corpora lutea represented by Day-12 implants was similar to egg recovery rates in animals similarly treated. The treatment had no effect on fetal survival from Day 12 to 28 of pregnancy. The decrease in fertility caused by these vaginal suppositories is presumably due to the stimulatory effect on oviductal motility which accelerates tubal transport of the embryos into the uterus. Embryos that arrive in the uterus prematurely probably do not implant and degenerate or are expelled."} {"id": "PMID:1257261", "title": "Hypercholesterolemia due to ascorbic acid.", "content": "Rats fed a purified diet containing ascorbic acid developed hypercholesterolemia. Because rats do not require exogenous ascorbic acid, they may be comparable to humans who supplement their diets with ascorbic acid in capsular form. The amount of ascorbic acid in this experiment was equivalent to 82 to 630 mg of capsular ascorbic acid ingested by an average man and was well below the amount ingested by those in search of respiratory benefit. The data are consonant with those on humans consuming controlled diets.", "contents": "Hypercholesterolemia due to ascorbic acid. Rats fed a purified diet containing ascorbic acid developed hypercholesterolemia. Because rats do not require exogenous ascorbic acid, they may be comparable to humans who supplement their diets with ascorbic acid in capsular form. The amount of ascorbic acid in this experiment was equivalent to 82 to 630 mg of capsular ascorbic acid ingested by an average man and was well below the amount ingested by those in search of respiratory benefit. The data are consonant with those on humans consuming controlled diets."} {"id": "PMID:1257262", "title": "In vitro colony assay for a new class of megakaryocyte precursor: colony-forming unit megakaryocyte (CFU-M).", "content": "A plasma culture system has been used successfully to grow and quantitate megakaryocyte colonies from mouse bone marrow following their staining for acetylcholinesterase activity in situ. Colonies averaging about six acetylcholinesterase-positive cells appear with a peak incidence after 4 days in culture with a plating efficiency of one colony formed for every 10(4) nucleated cells plated.", "contents": "In vitro colony assay for a new class of megakaryocyte precursor: colony-forming unit megakaryocyte (CFU-M). A plasma culture system has been used successfully to grow and quantitate megakaryocyte colonies from mouse bone marrow following their staining for acetylcholinesterase activity in situ. Colonies averaging about six acetylcholinesterase-positive cells appear with a peak incidence after 4 days in culture with a plating efficiency of one colony formed for every 10(4) nucleated cells plated."} {"id": "PMID:1257263", "title": "Estrogen-progestogen interaction: factors influencing progesterone-induced endometrial changes of the uterus of the immature rabbit.", "content": "In orally estrogen-primed animals, four times as much progesterone is required to bring about secretory changes comparable to those obtained following subcutaneous priming. These findings might be interpreted as evidence that: (a) oral estrogen-induced proliferative changes are either different or inadequate, and (b) excess progesterone is conditio sine qua non for the induction of those proliferative changes susceptible of being transformed into secretory ones.", "contents": "Estrogen-progestogen interaction: factors influencing progesterone-induced endometrial changes of the uterus of the immature rabbit. In orally estrogen-primed animals, four times as much progesterone is required to bring about secretory changes comparable to those obtained following subcutaneous priming. These findings might be interpreted as evidence that: (a) oral estrogen-induced proliferative changes are either different or inadequate, and (b) excess progesterone is conditio sine qua non for the induction of those proliferative changes susceptible of being transformed into secretory ones."} {"id": "PMID:1257264", "title": "The influence of hypophysectomy on the stores of somatostatin in the hypothalamuu and pituitary stem.", "content": "Twenty-eight to 133 days after hypophysectomy of the rat, somatostatin as revealed immunocytochemically was depleted from all segments of the median eminence and from the proximal part of the infundibular stem. A consistent change in the store of somatostatin in the OVLT could not be demonstrated.", "contents": "The influence of hypophysectomy on the stores of somatostatin in the hypothalamuu and pituitary stem. Twenty-eight to 133 days after hypophysectomy of the rat, somatostatin as revealed immunocytochemically was depleted from all segments of the median eminence and from the proximal part of the infundibular stem. A consistent change in the store of somatostatin in the OVLT could not be demonstrated."} {"id": "PMID:1257265", "title": "Nonparallel courses of intrapancreatic levels of exportable enzymes after a fatty meal.", "content": "Stimulation of pancreatic secretion by a fatty meal resulted in a nonparallel time-course of intrapancreatic amylase, lipase, trypsinogen, and chymotrypsinogen levels. Concomitant variations in the rate of pancreatic protein biosynthesis are observed. Those results support the hypothesis that nonparallelism in exportable enzyme levels is a consequence of a nonparallel regulation by the stimulus of the individual rates of enzyme biosynthesis.", "contents": "Nonparallel courses of intrapancreatic levels of exportable enzymes after a fatty meal. Stimulation of pancreatic secretion by a fatty meal resulted in a nonparallel time-course of intrapancreatic amylase, lipase, trypsinogen, and chymotrypsinogen levels. Concomitant variations in the rate of pancreatic protein biosynthesis are observed. Those results support the hypothesis that nonparallelism in exportable enzyme levels is a consequence of a nonparallel regulation by the stimulus of the individual rates of enzyme biosynthesis."} {"id": "PMID:1257266", "title": "Attenuation of hypoxic pulmonary vasoconstriction by verapamil in intact dogs.", "content": "The hypothesis that hypoxic pulmonary vasoconstriction is mediated directly by depolarization of the vascular smooth muscle was tested in anesthetized dogs. Pulmonary vascular responses to hypoxia were first determined in eight dogs during 20-min exposures to 10% O2. Each animal was then treated with verapamil (0.5 mg/kg, iv), to block transmembrane Ca2+ influx in an attempt to abolish the vasoconstrictor responses to hypoxia. The hypoxic exposures were then repeated, and the pulmonary vascular responses were compared to the control responses. Verapamil administration attenuated hypoxic pulmonary vasoconstriction, but did not abolish the responses to hypoxia. Pulmonary vascular resistance increased 87% during the control hypoxic exposure, but increased only 38% during hypoxia after verapamil. The response to another vasoconstrictor, prostaglandin F2alpha, was not reduced by verapamil indicating a different mechanism of mediation. These results suggest that the pulmonary vasoconstrictor response to alveolar hypoxia, in the intact dog, involves transmembrane Ca2+ influx, and are consistent with the idea that hypoxia acts primarily by directly depolarizing vascular smooth muscle, rather than acting indirectly through a chemical mediator.", "contents": "Attenuation of hypoxic pulmonary vasoconstriction by verapamil in intact dogs. The hypothesis that hypoxic pulmonary vasoconstriction is mediated directly by depolarization of the vascular smooth muscle was tested in anesthetized dogs. Pulmonary vascular responses to hypoxia were first determined in eight dogs during 20-min exposures to 10% O2. Each animal was then treated with verapamil (0.5 mg/kg, iv), to block transmembrane Ca2+ influx in an attempt to abolish the vasoconstrictor responses to hypoxia. The hypoxic exposures were then repeated, and the pulmonary vascular responses were compared to the control responses. Verapamil administration attenuated hypoxic pulmonary vasoconstriction, but did not abolish the responses to hypoxia. Pulmonary vascular resistance increased 87% during the control hypoxic exposure, but increased only 38% during hypoxia after verapamil. The response to another vasoconstrictor, prostaglandin F2alpha, was not reduced by verapamil indicating a different mechanism of mediation. These results suggest that the pulmonary vasoconstrictor response to alveolar hypoxia, in the intact dog, involves transmembrane Ca2+ influx, and are consistent with the idea that hypoxia acts primarily by directly depolarizing vascular smooth muscle, rather than acting indirectly through a chemical mediator."} {"id": "PMID:1257267", "title": "Influence of dietary fluoride restriction on regulation of plasma nd soft tissue fluoride contents.", "content": "The adjustments in total fluoride concentration in plasma, bones, liver, and muscle were examined when rats were given a diet of very low fluoride content following a dietary regimen of elevated fluoride intake. The animals received a diet containing 34 ppm of fluoride and water with 50 ppm added fluoride in the 28-day initial period and in the depletion period they were given a diet containing only 0.21 ppm of fluoride and distilled water. The findings indicated a 12-fold increase in the fluoride content of the humeri after 28 days of high-flurodie intake with a greater increment by the epiphyses than by the diaphyses. During 21 days of the depletion period the skeletal fluoride was reduced by only 7.7% indicating a marked retention of fluoride during processes of bone remodeling and growth. The plasma, muscle, and liver total fluoride contents were significantly increased at the end of the period of high-fluoride intake, but these concentrations were found to be restored to base-line levels in 3-7 days of the depletion period. By comparison of the distribution of total fluoride with injected radiofluoride between tissue and plasma waters, it was concluded that muscle and liver contain bound fluoride that does not exchange completely with ionic fluoride.", "contents": "Influence of dietary fluoride restriction on regulation of plasma nd soft tissue fluoride contents. The adjustments in total fluoride concentration in plasma, bones, liver, and muscle were examined when rats were given a diet of very low fluoride content following a dietary regimen of elevated fluoride intake. The animals received a diet containing 34 ppm of fluoride and water with 50 ppm added fluoride in the 28-day initial period and in the depletion period they were given a diet containing only 0.21 ppm of fluoride and distilled water. The findings indicated a 12-fold increase in the fluoride content of the humeri after 28 days of high-flurodie intake with a greater increment by the epiphyses than by the diaphyses. During 21 days of the depletion period the skeletal fluoride was reduced by only 7.7% indicating a marked retention of fluoride during processes of bone remodeling and growth. The plasma, muscle, and liver total fluoride contents were significantly increased at the end of the period of high-fluoride intake, but these concentrations were found to be restored to base-line levels in 3-7 days of the depletion period. By comparison of the distribution of total fluoride with injected radiofluoride between tissue and plasma waters, it was concluded that muscle and liver contain bound fluoride that does not exchange completely with ionic fluoride."} {"id": "PMID:1257273", "title": "Study of local anesthetics. Part 46: Correlations between anesthetic activity and physico-chemical parameters of some alkoxy substituted esters of phenylcarbamic acids.", "content": "The partition in water-octanol and water-carbon tetrachloride systems and electronic spectra of three series of esters of phenylcarbamic acid and its m- and p-alkoxy derivatives were measured. The surface local anesthetic activity of these compounds as well as the infiltration anesthetic activity of some of them were correlated with combinations of partition coefficients, spectral parameters and sigma-coefficients.", "contents": "Study of local anesthetics. Part 46: Correlations between anesthetic activity and physico-chemical parameters of some alkoxy substituted esters of phenylcarbamic acids. The partition in water-octanol and water-carbon tetrachloride systems and electronic spectra of three series of esters of phenylcarbamic acid and its m- and p-alkoxy derivatives were measured. The surface local anesthetic activity of these compounds as well as the infiltration anesthetic activity of some of them were correlated with combinations of partition coefficients, spectral parameters and sigma-coefficients."} {"id": "PMID:1257287", "title": "Transfer dosemeters for fast neutron sources.", "content": "The increasing use of fast neutron sources in radiobiology, radiotherapy, etc. makes dosimetry intercomparisons (intercalibrations) by mail desirable. After comparing the relative advantages and disadvantages of the various available integrating fast neutron detectors, fission fragment track etching was chosen because such detectors can be made sufficiently small, rugged, fading resistant, inexpensive and accurate. Using several combinations of 232Th or 237Np as fissile materials, and organic and inorganic track detectors, it was established that both automatic spark counting and visual track counting techniques can be developed to cover the desirable dose range (approximately 50-500 rad) with sufficient accuracy (sigma less than or equal to 5%). One possible source of errors is the overlapping size distributions of fission fragment and recoil particle tracks in organic foils exposed at high neutron energies. Several approaches to reduce this problem are discussed.", "contents": "Transfer dosemeters for fast neutron sources. The increasing use of fast neutron sources in radiobiology, radiotherapy, etc. makes dosimetry intercomparisons (intercalibrations) by mail desirable. After comparing the relative advantages and disadvantages of the various available integrating fast neutron detectors, fission fragment track etching was chosen because such detectors can be made sufficiently small, rugged, fading resistant, inexpensive and accurate. Using several combinations of 232Th or 237Np as fissile materials, and organic and inorganic track detectors, it was established that both automatic spark counting and visual track counting techniques can be developed to cover the desirable dose range (approximately 50-500 rad) with sufficient accuracy (sigma less than or equal to 5%). One possible source of errors is the overlapping size distributions of fission fragment and recoil particle tracks in organic foils exposed at high neutron energies. Several approaches to reduce this problem are discussed."} {"id": "PMID:1257288", "title": "The dosimetry of radioisotopes incorporated in bone using cavity ionization theory.", "content": "Cavity ionization theory is applied to the dosimetry of bones incorporating beta- and gamma-emitting radioactive isotopes. The assumptions inherent in different theoretical approaches to bone dosimetry are reviewed and compared with those adopted in cavity theory. In presenting the theory attention is given to the effects of electron and photon attenuation and to the absence of electronic equilibrium which may occur in bone. The mean marrow dose is calculated for a range of cavity size and gamma-ray energies and for a beta-ray emitter. The mean marrow dose and the mean endosteal dose are calculated for a human lumbar vertebra and some comparisons made with the results of other workers. It is concluded that cavity theory provides a useful approach to the dosimetry problems of bone-seeking beta- and gamma-ray radioactive isotopes.", "contents": "The dosimetry of radioisotopes incorporated in bone using cavity ionization theory. Cavity ionization theory is applied to the dosimetry of bones incorporating beta- and gamma-emitting radioactive isotopes. The assumptions inherent in different theoretical approaches to bone dosimetry are reviewed and compared with those adopted in cavity theory. In presenting the theory attention is given to the effects of electron and photon attenuation and to the absence of electronic equilibrium which may occur in bone. The mean marrow dose is calculated for a range of cavity size and gamma-ray energies and for a beta-ray emitter. The mean marrow dose and the mean endosteal dose are calculated for a human lumbar vertebra and some comparisons made with the results of other workers. It is concluded that cavity theory provides a useful approach to the dosimetry problems of bone-seeking beta- and gamma-ray radioactive isotopes."} {"id": "PMID:1257289", "title": "Conditions under which a number of sinusoids may be instantaneously in phase.", "content": "The literature on the phase relationships between frequency components of a Fourier analysis is reviewed, with examples and theories from acoustics and neurophysiology. Given n sinusoids of different frequencies omega1, omega2, .., omegan and phase angles phi1, phi2, .., phin, it is shown that for n greater than or equal to 2 the set of initial phase angles allowing the n sinusoids to be in phase at some time t0 consists of one or more planes of constant dimension 2 and that for n = 2 such a time t0 always exists. The conditions under which the common phase of n sinusoids at one time t0 will be the same as the common phase at another time t0 are also investigated. The importance of incommensurately related frequency components is emphasized by proofs which do not depend on harmonic relationships. Proofs are formulated in a linear algebra format to demonstrate the versatility of the method for analysing long sequences of frequencies and phases.", "contents": "Conditions under which a number of sinusoids may be instantaneously in phase. The literature on the phase relationships between frequency components of a Fourier analysis is reviewed, with examples and theories from acoustics and neurophysiology. Given n sinusoids of different frequencies omega1, omega2, .., omegan and phase angles phi1, phi2, .., phin, it is shown that for n greater than or equal to 2 the set of initial phase angles allowing the n sinusoids to be in phase at some time t0 consists of one or more planes of constant dimension 2 and that for n = 2 such a time t0 always exists. The conditions under which the common phase of n sinusoids at one time t0 will be the same as the common phase at another time t0 are also investigated. The importance of incommensurately related frequency components is emphasized by proofs which do not depend on harmonic relationships. Proofs are formulated in a linear algebra format to demonstrate the versatility of the method for analysing long sequences of frequencies and phases."} {"id": "PMID:1257290", "title": "Infrasonic analysis of carotid vibration as a diagnostic method in carotid insufficiency syndrome.", "content": "The infrasonic part of the spectrum of the carotid artery wall vibration in the neck was obtained. Differences between the spectral content and vibrational amplitude in normal and occluded carotids were found. The application of this technique in clinical practice could be useful in the detection of the carotid insufficiency syndrome.", "contents": "Infrasonic analysis of carotid vibration as a diagnostic method in carotid insufficiency syndrome. The infrasonic part of the spectrum of the carotid artery wall vibration in the neck was obtained. Differences between the spectral content and vibrational amplitude in normal and occluded carotids were found. The application of this technique in clinical practice could be useful in the detection of the carotid insufficiency syndrome."} {"id": "PMID:1257296", "title": "Calculated beta-ray dose factors for trabecular bone.", "content": "Mean dose factors have been calculated for those tissues in bone that are relevant to the induction of late irradiation effects; namely, red bone marrow and endosteal tissues lining trabecular bone surfaces. The calculations are based on a Monte Carlo computer method for beta-emitting radionuclides which are distributed uniformly throughout the volume of mineralized bone. Results are given for the radionuclides 14C, 45Ca, 22Na, 18F, 32P, 90Y and 90Sr+90Y (all considered for this purpose as volume-seekers) for seven bones from the adult human skeleton and calculations are also presented of average skeletal dose factors. Where possible, results are compared with those derived from other methods based on simple geometrical models.", "contents": "Calculated beta-ray dose factors for trabecular bone. Mean dose factors have been calculated for those tissues in bone that are relevant to the induction of late irradiation effects; namely, red bone marrow and endosteal tissues lining trabecular bone surfaces. The calculations are based on a Monte Carlo computer method for beta-emitting radionuclides which are distributed uniformly throughout the volume of mineralized bone. Results are given for the radionuclides 14C, 45Ca, 22Na, 18F, 32P, 90Y and 90Sr+90Y (all considered for this purpose as volume-seekers) for seven bones from the adult human skeleton and calculations are also presented of average skeletal dose factors. Where possible, results are compared with those derived from other methods based on simple geometrical models."} {"id": "PMID:1257297", "title": "A TLD system based on lithium borate for the measurement of doses to patients undergoing medical irradiation.", "content": "A dosimetry system has been developed which is especially suited to the measurement of doses to patients undergoing irradiation for medical purposes. It is a TLD system based on lithium borate which has been used both in powder form and made up into solid discs by incorporation within PTFE. The predominant advantages of this material over other more widely used TLD materials are its closer approximation to soft tissue, its simple glow curve which eliminates the need for complicated annealing procedures and its low cost. The luminescence from the lithium borate is measured with a specially designed reader which uses radiofrequency heating. At present, using lithium borate powder, the system is capable of measuring doses down to 10 mrad and using lithium borate/PTFE discs it can measure down to 50 mrad with adequate precision. Preliminary measurements on solid glassy discs of lithium borate suggest that this form of the material may in some respects be superior for patient dosimetry.", "contents": "A TLD system based on lithium borate for the measurement of doses to patients undergoing medical irradiation. A dosimetry system has been developed which is especially suited to the measurement of doses to patients undergoing irradiation for medical purposes. It is a TLD system based on lithium borate which has been used both in powder form and made up into solid discs by incorporation within PTFE. The predominant advantages of this material over other more widely used TLD materials are its closer approximation to soft tissue, its simple glow curve which eliminates the need for complicated annealing procedures and its low cost. The luminescence from the lithium borate is measured with a specially designed reader which uses radiofrequency heating. At present, using lithium borate powder, the system is capable of measuring doses down to 10 mrad and using lithium borate/PTFE discs it can measure down to 50 mrad with adequate precision. Preliminary measurements on solid glassy discs of lithium borate suggest that this form of the material may in some respects be superior for patient dosimetry."} {"id": "PMID:1257298", "title": "Ultraviolet response of CaSO4:Dy.", "content": "A simple method for measuring ultraviolet exposure using the thermoluminescent properties of CaSO4:Dy is presented in this paper. In general, three peaks at 145, 215 and 365 degrees C were observed by ultraviolet irradiation of virgin phosphor. The peak at 365 degrees C was found to be very small and that at 145 degrees C fades away within a week; no appreciable fading was observed for the 215 degrees C peak. Further, the peak at 215 degrees C was found to coincide with the gamma dosimetric peak and this peak was chosen for ultraviolet exposure measurements. A standard quartz pen-ray lamp was used for calibrating the phosphor both by peak height measurement and by integration. The dosimetric peak has been found to be linear from the detection threshold of 400 erg mm-2 to 4 X 10(4) erg mm-2. Beyond this exposure the phosphor behaved supralinearly to ultraviolet exposure up to the studied range of 5 X 10(5) erg mm-2. The phosphor exhibited strong dependence on photon energy. The TL sensitivity increases sharply by a factor of 300 as the wavelength is decreased from 250 to 200 nm. The response is negligibly small above 350 nm. Other important characteristics such as particle size dependence, fading characteristics, thickness dependence and re-usability are also presented. The ultraviolet sensitivity increased by a factor of 3 when the grain size range was changed from 105-210 mum. Self-shielding by a factor of 2 was observed when the sample thickness was increased from 10 to 72 mg cm-2.", "contents": "Ultraviolet response of CaSO4:Dy. A simple method for measuring ultraviolet exposure using the thermoluminescent properties of CaSO4:Dy is presented in this paper. In general, three peaks at 145, 215 and 365 degrees C were observed by ultraviolet irradiation of virgin phosphor. The peak at 365 degrees C was found to be very small and that at 145 degrees C fades away within a week; no appreciable fading was observed for the 215 degrees C peak. Further, the peak at 215 degrees C was found to coincide with the gamma dosimetric peak and this peak was chosen for ultraviolet exposure measurements. A standard quartz pen-ray lamp was used for calibrating the phosphor both by peak height measurement and by integration. The dosimetric peak has been found to be linear from the detection threshold of 400 erg mm-2 to 4 X 10(4) erg mm-2. Beyond this exposure the phosphor behaved supralinearly to ultraviolet exposure up to the studied range of 5 X 10(5) erg mm-2. The phosphor exhibited strong dependence on photon energy. The TL sensitivity increases sharply by a factor of 300 as the wavelength is decreased from 250 to 200 nm. The response is negligibly small above 350 nm. Other important characteristics such as particle size dependence, fading characteristics, thickness dependence and re-usability are also presented. The ultraviolet sensitivity increased by a factor of 3 when the grain size range was changed from 105-210 mum. Self-shielding by a factor of 2 was observed when the sample thickness was increased from 10 to 72 mg cm-2."} {"id": "PMID:1257299", "title": "A three-compartment model for the transport and distribution of Hippuran.", "content": "It is generally believed that after an intravenous injection of Hippuran its concentration in the plasma can be described as the sum of two exponentials. However, by collecting samples during the first minute after injection of the tracer, a third exponential term was found with a half-life of less than one minute. To explain its presence it was assumed that the plasma shares its Hippuran with two peripheral compartments, the rate of transfer from one compartment to another being proportional to the amount in the first of them. The proportionality factors have been determined for 20 adults and averaged. Substituting these averages in the differential equations for the distribution process, the only variable remaining is the renal excretion rate a (the fraction of plasma cleared per minute by the kidneys). If this procedure, which appears to be justified by the experimental results, is correct the shape of the plasma curve will be determined exclusively by a. It is shown that the (small) third compartment has a minor influence on the shape of the renogram curves.", "contents": "A three-compartment model for the transport and distribution of Hippuran. It is generally believed that after an intravenous injection of Hippuran its concentration in the plasma can be described as the sum of two exponentials. However, by collecting samples during the first minute after injection of the tracer, a third exponential term was found with a half-life of less than one minute. To explain its presence it was assumed that the plasma shares its Hippuran with two peripheral compartments, the rate of transfer from one compartment to another being proportional to the amount in the first of them. The proportionality factors have been determined for 20 adults and averaged. Substituting these averages in the differential equations for the distribution process, the only variable remaining is the renal excretion rate a (the fraction of plasma cleared per minute by the kidneys). If this procedure, which appears to be justified by the experimental results, is correct the shape of the plasma curve will be determined exclusively by a. It is shown that the (small) third compartment has a minor influence on the shape of the renogram curves."} {"id": "PMID:1257300", "title": "A neutron source with an effective energy of 0-5 keV.", "content": "Calculations indicate that an assembly consisting of an antimony-beryllium source at the centre of a 4 cm radius water sphere surrounded by a 1 mm thick shell of boron-10 will emit neutrons with a broad spectrum at intermediate energies. A device based on this design was constructed using a water-filled, boron-carbide loaded, plastic shell with an antimony-beryllium source located at the centre. The output spectrum was calculated by Monte Carlo program and the computed total yield agreed well with measurements made with a manganese bath system. The main peak has an effective energy of 0-5 keV and the total yield is 18% of the antimony-beryllium source strength. Experience with this source suggests some possible avenues for future development.", "contents": "A neutron source with an effective energy of 0-5 keV. Calculations indicate that an assembly consisting of an antimony-beryllium source at the centre of a 4 cm radius water sphere surrounded by a 1 mm thick shell of boron-10 will emit neutrons with a broad spectrum at intermediate energies. A device based on this design was constructed using a water-filled, boron-carbide loaded, plastic shell with an antimony-beryllium source located at the centre. The output spectrum was calculated by Monte Carlo program and the computed total yield agreed well with measurements made with a manganese bath system. The main peak has an effective energy of 0-5 keV and the total yield is 18% of the antimony-beryllium source strength. Experience with this source suggests some possible avenues for future development."} {"id": "PMID:1257301", "title": "A flow calorimetric method of determining electron beam energy.", "content": "The construction of an adiabatic flow calorimeter using water as the working substance is described. It is shown that at high dose rates the heat defect due to chemical reactions in water is small (of the order of 0-3%) and that under high dose rate conditions flow calorimetry can be used as a method of measuring the energy of high intensity electron beams. Measurements made with a 15 MeV linear accelerator are reported and compared with magnetic measurements.", "contents": "A flow calorimetric method of determining electron beam energy. The construction of an adiabatic flow calorimeter using water as the working substance is described. It is shown that at high dose rates the heat defect due to chemical reactions in water is small (of the order of 0-3%) and that under high dose rate conditions flow calorimetry can be used as a method of measuring the energy of high intensity electron beams. Measurements made with a 15 MeV linear accelerator are reported and compared with magnetic measurements."} {"id": "PMID:1257302", "title": "A thermoluminescence system for the intercomparison of absorbed dose and radiation quality of X-rays with a HVL of 0-1 to 3-0 mm Cu.", "content": "A TLD system is described which permits the measurement of absorbed X-ray doses in a water phantom, together with the quality of the incident X-ray beam. The system has been developed for dose and energy intercomparison studies between centres with deep therapy X-ray machines. A distinction has been made between deep therapy treatments and treatments at or near the surface. For beam qualities with a HVL above 1-1 mm Cu, the deep therapy region, measurements have been performed at 5 cm depth in water using CaF2: Mn and LiF (TLD 700). For beam qualities with a HVL of 0-11-1-4 mm Cu, these qualities include the superficial therapy region, measurements with LiF dosemeters at 2 and 10 cm depth in water have been carried out. The uncertainty in the absorbed dose value for X-ray beams with a HVL of 0-11-3-0 mm Cu amounts to +/- 4%; the uncertainty in the determination of the effective energy of the incident beam is +/- 3 to +/- 7%.", "contents": "A thermoluminescence system for the intercomparison of absorbed dose and radiation quality of X-rays with a HVL of 0-1 to 3-0 mm Cu. A TLD system is described which permits the measurement of absorbed X-ray doses in a water phantom, together with the quality of the incident X-ray beam. The system has been developed for dose and energy intercomparison studies between centres with deep therapy X-ray machines. A distinction has been made between deep therapy treatments and treatments at or near the surface. For beam qualities with a HVL above 1-1 mm Cu, the deep therapy region, measurements have been performed at 5 cm depth in water using CaF2: Mn and LiF (TLD 700). For beam qualities with a HVL of 0-11-1-4 mm Cu, these qualities include the superficial therapy region, measurements with LiF dosemeters at 2 and 10 cm depth in water have been carried out. The uncertainty in the absorbed dose value for X-ray beams with a HVL of 0-11-3-0 mm Cu amounts to +/- 4%; the uncertainty in the determination of the effective energy of the incident beam is +/- 3 to +/- 7%."} {"id": "PMID:1257303", "title": "Comparison of the particle size distribution curves determined manually and automatically in an accurately calibrated Coulter Counter.", "content": "An accurately calibrated Coulter Counter, Model ZB Industrial, was used to compare the size distribution curves of seven different standard particles obtained by calculation and after the attachment of a Channelyser, Model C-1000 coupled to an XY recorder. Comparisons were made at the modes of the curves and it was found that the automatic method consistently reported the particles to be slightly larger.", "contents": "Comparison of the particle size distribution curves determined manually and automatically in an accurately calibrated Coulter Counter. An accurately calibrated Coulter Counter, Model ZB Industrial, was used to compare the size distribution curves of seven different standard particles obtained by calculation and after the attachment of a Channelyser, Model C-1000 coupled to an XY recorder. Comparisons were made at the modes of the curves and it was found that the automatic method consistently reported the particles to be slightly larger."} {"id": "PMID:1257304", "title": "Influence of hole shape on collimator performance.", "content": "The imaging properties of triangular and hexagonal hole shapes were compared for low energy scintillation camera collimators. The response of both hole shapes was calculated using a ray-tracing computer program, corresponding collimators were constructed and their performance was evaluated by measuring line spread functions and imaging bar patterns. The triangular hole shape was found to give better results above a spatial frequency of 1-5 cycles cm-1, below that frequency the hexagonal hole shape is superior. The differences, however, are small and the superior performance of the hexagonal hole collimator at clinically significant spatial frequencies is barely visible in bar pattern images.", "contents": "Influence of hole shape on collimator performance. The imaging properties of triangular and hexagonal hole shapes were compared for low energy scintillation camera collimators. The response of both hole shapes was calculated using a ray-tracing computer program, corresponding collimators were constructed and their performance was evaluated by measuring line spread functions and imaging bar patterns. The triangular hole shape was found to give better results above a spatial frequency of 1-5 cycles cm-1, below that frequency the hexagonal hole shape is superior. The differences, however, are small and the superior performance of the hexagonal hole collimator at clinically significant spatial frequencies is barely visible in bar pattern images."} {"id": "PMID:1257305", "title": "Experience in the development of low haemolysis pumps.", "content": "In an attempt to provide a pulsatile pump with a low rate of haemolysis, two pulsatile pumps have been developed. These were compared with commercially available pulsatile and roller pumps. The blood flow and the rate of haemolysis were studied under similar conditions. Our pumps were significantly better than the commercial pumps as far as mechanical damage to the red blood cells was concerned. However, we carried out certain modifications to one of our pumps which resulted in a significant reduction in the amount of haemolysis over its previous performance.", "contents": "Experience in the development of low haemolysis pumps. In an attempt to provide a pulsatile pump with a low rate of haemolysis, two pulsatile pumps have been developed. These were compared with commercially available pulsatile and roller pumps. The blood flow and the rate of haemolysis were studied under similar conditions. Our pumps were significantly better than the commercial pumps as far as mechanical damage to the red blood cells was concerned. However, we carried out certain modifications to one of our pumps which resulted in a significant reduction in the amount of haemolysis over its previous performance."} {"id": "PMID:1257311", "title": "Physiological effects of passive exercise on cardiorespiratory function.", "content": "The purpose of this study was to determine the effects of passive exercise as performed by physical therapists on the cardiac and respiratory systems. Seventeen normal subjects were positioned supine on a treatment table where they received passive range-of-motion exercise manually of most joints of the right upper extremity for ten repetitions. Heart rate, respiratory rate, and tidal lung volume were recorded before and immediately after the exercise. The results of the study showed no significant difference between measured values.", "contents": "Physiological effects of passive exercise on cardiorespiratory function. The purpose of this study was to determine the effects of passive exercise as performed by physical therapists on the cardiac and respiratory systems. Seventeen normal subjects were positioned supine on a treatment table where they received passive range-of-motion exercise manually of most joints of the right upper extremity for ten repetitions. Heart rate, respiratory rate, and tidal lung volume were recorded before and immediately after the exercise. The results of the study showed no significant difference between measured values."} {"id": "PMID:1257312", "title": "Evaluating treatment effectiveness in cerebral palsy. Single-subject designs.", "content": "Methods to empirically evaluate treatment effectiveness for individual patients or small groups of patients are presented. Different types of single-subject (as opposed to group) experimental designs are described, and their appropriateness for heterogeneous populations such as the cerebral palsied is discussed. Possible errors in attributing causality are noted and illustrated. Techniques or behavioral analysis and various types of single-subject designs are presented, including the AB, ABA, ABAB, and multiple baseline across subjects, behaviors, and settings. The procedures are shown to produce reliable data from which conclusions about the relationship between treatment and behavior change can be made. The generalizability of single subject methods to different patients and problems is also discussed.", "contents": "Evaluating treatment effectiveness in cerebral palsy. Single-subject designs. Methods to empirically evaluate treatment effectiveness for individual patients or small groups of patients are presented. Different types of single-subject (as opposed to group) experimental designs are described, and their appropriateness for heterogeneous populations such as the cerebral palsied is discussed. Possible errors in attributing causality are noted and illustrated. Techniques or behavioral analysis and various types of single-subject designs are presented, including the AB, ABA, ABAB, and multiple baseline across subjects, behaviors, and settings. The procedures are shown to produce reliable data from which conclusions about the relationship between treatment and behavior change can be made. The generalizability of single subject methods to different patients and problems is also discussed."} {"id": "PMID:1257319", "title": "[The instability of word-final alveolar plosives in German: an electropalatographic investigation (author's transl)].", "content": "Descriptive autority analyses of continuous texts in German have shown that word-final alveolar plosives are frequently assimilated to following labials and velars. On the basis of illustrative data this experimental investigation deals with the question of whether the alveolar movement is completely eliminated by articulatory control or whether coarticulation arises which involves the preservation of the articulatory gesture without a perceptual consequence. As regards the experimental procedure, a method of dynamic palatography is used and described here, also in respect of its limitations. Material from one subject is then discussed and the direction of future research in this area outlined with regard to new experiments and the necessary instrumental facilities. Finally, the special articulatory and physiological status of alveolar consonants in general is considered as well as ensuing consequences for sound change.", "contents": "[The instability of word-final alveolar plosives in German: an electropalatographic investigation (author's transl)]. Descriptive autority analyses of continuous texts in German have shown that word-final alveolar plosives are frequently assimilated to following labials and velars. On the basis of illustrative data this experimental investigation deals with the question of whether the alveolar movement is completely eliminated by articulatory control or whether coarticulation arises which involves the preservation of the articulatory gesture without a perceptual consequence. As regards the experimental procedure, a method of dynamic palatography is used and described here, also in respect of its limitations. Material from one subject is then discussed and the direction of future research in this area outlined with regard to new experiments and the necessary instrumental facilities. Finally, the special articulatory and physiological status of alveolar consonants in general is considered as well as ensuing consequences for sound change."} {"id": "PMID:1257320", "title": "[Radiological aspects of emotive speech (author's transl)].", "content": "The mechanism for the acoustic encoding of emotions was analyzed by means of two X-ray films containing neutral and emotional variants (anger, hate, sadness, joy, tenderness, irony) of six Hungarian phrases. Each attitude is expressed by an articulatory pattern peculiar to it. This oral gesture can be seen as superimposed on the (ideal) neutral articulation. Each concrete sound necessarily contains two pieces of information differing profoundly both at the level of content (conceptual vs. preconceptual) and of expression (arbitrary linguistics vs. non-arbitrary prelinguistic encoding). In some cases, this double encoding is reflected in ambiguous and contradictory lingual articulation.", "contents": "[Radiological aspects of emotive speech (author's transl)]. The mechanism for the acoustic encoding of emotions was analyzed by means of two X-ray films containing neutral and emotional variants (anger, hate, sadness, joy, tenderness, irony) of six Hungarian phrases. Each attitude is expressed by an articulatory pattern peculiar to it. This oral gesture can be seen as superimposed on the (ideal) neutral articulation. Each concrete sound necessarily contains two pieces of information differing profoundly both at the level of content (conceptual vs. preconceptual) and of expression (arbitrary linguistics vs. non-arbitrary prelinguistic encoding). In some cases, this double encoding is reflected in ambiguous and contradictory lingual articulation."} {"id": "PMID:1257321", "title": "On the predictive role of the recent theories of aspiration.", "content": "The purpose of this study is to examine the predictive power of recent theories of aspiration. These theories (lag of voicing) predict that aspirated sounds will be perceived as unaspirated in word-final position, as in the case of Korean stops. Contrary to the predictions of these theories, our experiment showed that in final position in Hindi stops, such a neutralization between unaspirated and aspirated stops was absent. What is even more interesting is that the intelligibility of aspirated sounds in Hindi was the highest on the perception scale while unaspirated had a lower rank.", "contents": "On the predictive role of the recent theories of aspiration. The purpose of this study is to examine the predictive power of recent theories of aspiration. These theories (lag of voicing) predict that aspirated sounds will be perceived as unaspirated in word-final position, as in the case of Korean stops. Contrary to the predictions of these theories, our experiment showed that in final position in Hindi stops, such a neutralization between unaspirated and aspirated stops was absent. What is even more interesting is that the intelligibility of aspirated sounds in Hindi was the highest on the perception scale while unaspirated had a lower rank."} {"id": "PMID:1257335", "title": "The cross-hand finger transfer.", "content": "This report is of the first successful case we know of transplantation of a ray (finger and metacarpal) from one hand to another. The transfer was accomplished by a two-stage pedicle technique. The tendons and nerves were left long in the donor finger, and were anastomosed at the second stage when the pedicle was divided. Good sensation was obtained. Active tendon function resulted, with excellent power and range of motion in all of the digits of both hands.", "contents": "The cross-hand finger transfer. This report is of the first successful case we know of transplantation of a ray (finger and metacarpal) from one hand to another. The transfer was accomplished by a two-stage pedicle technique. The tendons and nerves were left long in the donor finger, and were anastomosed at the second stage when the pedicle was divided. Good sensation was obtained. Active tendon function resulted, with excellent power and range of motion in all of the digits of both hands."} {"id": "PMID:1257337", "title": "Postoperative hypertension as an etiological factor in hematoma after rhytidectomy. Prevention with chlorpromazine.", "content": "Our experience strongly implicates postoperative \"reactive hypertension\" as a major etiological factor in hematoma formation in the face lift patient. This autonomic lability to post-surgical and emotional stress may be prevented and treated by the appropriate and timely administration of chlorpromazine.", "contents": "Postoperative hypertension as an etiological factor in hematoma after rhytidectomy. Prevention with chlorpromazine. Our experience strongly implicates postoperative \"reactive hypertension\" as a major etiological factor in hematoma formation in the face lift patient. This autonomic lability to post-surgical and emotional stress may be prevented and treated by the appropriate and timely administration of chlorpromazine."} {"id": "PMID:1257338", "title": "A scanning electron microscope study of microvascular anastomoses.", "content": "The abdominal aortas of 30 rats were sutured under an operating microscope. The results were studied under a scanning electron microscope at 8 different periods after operation, ranging from 3 minutes to one month. The observations are presented.", "contents": "A scanning electron microscope study of microvascular anastomoses. The abdominal aortas of 30 rats were sutured under an operating microscope. The results were studied under a scanning electron microscope at 8 different periods after operation, ranging from 3 minutes to one month. The observations are presented."} {"id": "PMID:1257339", "title": "Preservation of a posterior pharyngeal flap during maxillary advancement.", "content": "In maxillary advancement procedures, a previously existing posterior pharyngeal flap can be preserved by lengthening it. A technique for this and its results in two cases are presented.", "contents": "Preservation of a posterior pharyngeal flap during maxillary advancement. In maxillary advancement procedures, a previously existing posterior pharyngeal flap can be preserved by lengthening it. A technique for this and its results in two cases are presented."} {"id": "PMID:1257340", "title": "Ankylosis of the mandible from cancrum oris.", "content": "We present 30 cases of ankylosis of the lower jaw following cancrum oris. The clinical and radiological findings, the anesthetic methods, and the surgical management are described. Adequate excision of limiting scar and any bony ankylosis, with immediate mucosal or skin coverage of any raw surfaces created, is the proper approach. Postoperative jaw exercises and the use of a bite block may be helpful.", "contents": "Ankylosis of the mandible from cancrum oris. We present 30 cases of ankylosis of the lower jaw following cancrum oris. The clinical and radiological findings, the anesthetic methods, and the surgical management are described. Adequate excision of limiting scar and any bony ankylosis, with immediate mucosal or skin coverage of any raw surfaces created, is the proper approach. Postoperative jaw exercises and the use of a bite block may be helpful."} {"id": "PMID:1257341", "title": "Spontaneous regression of the primary lesion of a metastatic maligvant melanoma.", "content": "An atypical elderly patient with spontaneous regression of a primary lesion of malignant melanoma is presented. The 12 previously reported cases are also reviewed. The histological diagnosis of spontaneous regression of a melanoma can still be made after the regression appears to be grossly complete. All localized areas of depigmentation, or of scarring, should be biopsied when searching for an \"occult\" primary.", "contents": "Spontaneous regression of the primary lesion of a metastatic maligvant melanoma. An atypical elderly patient with spontaneous regression of a primary lesion of malignant melanoma is presented. The 12 previously reported cases are also reviewed. The histological diagnosis of spontaneous regression of a melanoma can still be made after the regression appears to be grossly complete. All localized areas of depigmentation, or of scarring, should be biopsied when searching for an \"occult\" primary."} {"id": "PMID:1257347", "title": "The use of behavior modification therapy in a recalcitrant burned child: case report.", "content": "The hospital behavior of a burned adolescent is presented, with emphasis on the antecedent causes. We used a behavior modification technique to treat this patient, and we describe the basic characteristics of this procedure.", "contents": "The use of behavior modification therapy in a recalcitrant burned child: case report. The hospital behavior of a burned adolescent is presented, with emphasis on the antecedent causes. We used a behavior modification technique to treat this patient, and we describe the basic characteristics of this procedure."} {"id": "PMID:1257350", "title": "The role of anionic, imidic and amidic forms in structure-activity relationships. Conjugation and bacteriostatic activity in sulphonamides.", "content": "The electronic structures of anionic, imidic and amidic forms of sulphonamides were investigated and compared by means of I.R., Raman and U.V. spectroscopy. Indices reflecting the electronic situation of the common moiety p-H2N-C6H4-SO2 was a whole, although not necessarily related, physically, to any event taking place in the biological processes, were found to correlate with the in vitro bacteriostatic activity of the specific individual forms. The influence of N1-substituents both on the SO2 electronic features and on the coupling between the para amino group and the phenyl ring was discussed. It resulted that the most active chemical species, in this class of compounds, are characterized, electronically, by the most electron-rich common moiety and, in particular, by the most negative oxygens in the SO2 group and the most available (less engaged) lone-pair in the rho-amino group. These conclusions give a new settlement both to the problem of resonance and to the relation between resonance effects and bacteriostatic activity in this class of compounds.", "contents": "The role of anionic, imidic and amidic forms in structure-activity relationships. Conjugation and bacteriostatic activity in sulphonamides. The electronic structures of anionic, imidic and amidic forms of sulphonamides were investigated and compared by means of I.R., Raman and U.V. spectroscopy. Indices reflecting the electronic situation of the common moiety p-H2N-C6H4-SO2 was a whole, although not necessarily related, physically, to any event taking place in the biological processes, were found to correlate with the in vitro bacteriostatic activity of the specific individual forms. The influence of N1-substituents both on the SO2 electronic features and on the coupling between the para amino group and the phenyl ring was discussed. It resulted that the most active chemical species, in this class of compounds, are characterized, electronically, by the most electron-rich common moiety and, in particular, by the most negative oxygens in the SO2 group and the most available (less engaged) lone-pair in the rho-amino group. These conclusions give a new settlement both to the problem of resonance and to the relation between resonance effects and bacteriostatic activity in this class of compounds."} {"id": "PMID:1257359", "title": "Effect of clozapine on the metabolism of serotonin in rat brain.", "content": "Clozapine, but not chlorpromazine, haloperidol, thioridazine, or loxapine, increases the concentrations of tryptophan, serotonin, and 5-hydroxyindoleacetic acid in the brain of the rat. This effect of clozapine is due to an increased serotonin synthesis as demonstrated by an enhanced accumulation of 3H-serotonin in the brain after i.v. infusion of 3H-tryptophan. Clozapine also elevates the plasma concentration of free tryptophan, and reduces the plasma concentration of total tryptophan. Therefore, clozapine may increase the brain serotonin concentration by enhancing the availability of tryptophan in the brain, thereby promoting serotonin synthesis. Measurement of the rate of disappearance from the brain of 3H-serotonin or of endogenous serotonin after synthesis inhibition with 6-fluorotryptophan shows that clozapine has no direct effect on the release and degradation of serotonin. The effect of clozapine on brain serotonergic systems may possibly be related to the pronounced sedative and sleep-inducing properties of this drug.", "contents": "Effect of clozapine on the metabolism of serotonin in rat brain. Clozapine, but not chlorpromazine, haloperidol, thioridazine, or loxapine, increases the concentrations of tryptophan, serotonin, and 5-hydroxyindoleacetic acid in the brain of the rat. This effect of clozapine is due to an increased serotonin synthesis as demonstrated by an enhanced accumulation of 3H-serotonin in the brain after i.v. infusion of 3H-tryptophan. Clozapine also elevates the plasma concentration of free tryptophan, and reduces the plasma concentration of total tryptophan. Therefore, clozapine may increase the brain serotonin concentration by enhancing the availability of tryptophan in the brain, thereby promoting serotonin synthesis. Measurement of the rate of disappearance from the brain of 3H-serotonin or of endogenous serotonin after synthesis inhibition with 6-fluorotryptophan shows that clozapine has no direct effect on the release and degradation of serotonin. The effect of clozapine on brain serotonergic systems may possibly be related to the pronounced sedative and sleep-inducing properties of this drug."} {"id": "PMID:1257360", "title": "Acute and chronic effects of 4-chloroamphetamine on monoamine metabolism in the rat brain.", "content": "The acute administration of 4-chloroamphetamine caused a marked reduction in the concentration of serotonin and 5-hydroxyindoleacetic acid and a rise in dopamine in the rat brain. Following the injection of 3H-tyrosine and 3H-tryptophane into rats treated with 4-chloroamphetamine, there was a reduction in brain levels of 3H-dopamine and 3H-serotonin. Although the endogenous concentration of noradrenaline was not affected by 4-chloroamphetamine, there is evidence that its reuptake into neurones was reduced and its release increased by the drug. Following the administration of 4-chloroamphetamine for 10 days, the concentration of 5-hydroxyindoleacetic acid was reduced; no other changes in amine metabolism were apparent. From this investigation, and those of others, it appears that following acute administration, 4-chloroamphetamine has a neurochemical profile which has a similarity to that of many tricyclic antidepressants. However, there is a marked discrepancy between the acute and chronic effects of 4-CA on brain amine metabolism. Such findings are difficult to reconcile with the widely accepted theory that antidepressant drugs counteract the symptoms of depression by increasing the concentration of noradrenaline and/or serotonin at receptor sites within the brain.", "contents": "Acute and chronic effects of 4-chloroamphetamine on monoamine metabolism in the rat brain. The acute administration of 4-chloroamphetamine caused a marked reduction in the concentration of serotonin and 5-hydroxyindoleacetic acid and a rise in dopamine in the rat brain. Following the injection of 3H-tyrosine and 3H-tryptophane into rats treated with 4-chloroamphetamine, there was a reduction in brain levels of 3H-dopamine and 3H-serotonin. Although the endogenous concentration of noradrenaline was not affected by 4-chloroamphetamine, there is evidence that its reuptake into neurones was reduced and its release increased by the drug. Following the administration of 4-chloroamphetamine for 10 days, the concentration of 5-hydroxyindoleacetic acid was reduced; no other changes in amine metabolism were apparent. From this investigation, and those of others, it appears that following acute administration, 4-chloroamphetamine has a neurochemical profile which has a similarity to that of many tricyclic antidepressants. However, there is a marked discrepancy between the acute and chronic effects of 4-CA on brain amine metabolism. Such findings are difficult to reconcile with the widely accepted theory that antidepressant drugs counteract the symptoms of depression by increasing the concentration of noradrenaline and/or serotonin at receptor sites within the brain."} {"id": "PMID:1257361", "title": "Tolerance in methylphenidate-induced locomotion in prairie dogs (Cynomys ludovicianus).", "content": "After a five-day adaptation period in activity wheels, four prairie dogs were assigned to a methylphenidate group (2.5 mg/kg, s.c.) and four prairie dogs were assigned to a saline group for ten consecutive daily injections. Half-revolutions of locomotor activity were recorded during seven measurement periods taken daily. During the third measurement period, from 1-3 hrs following injection, the methylphenidate group declined in locomotor activity over the first three days of drug administration.", "contents": "Tolerance in methylphenidate-induced locomotion in prairie dogs (Cynomys ludovicianus). After a five-day adaptation period in activity wheels, four prairie dogs were assigned to a methylphenidate group (2.5 mg/kg, s.c.) and four prairie dogs were assigned to a saline group for ten consecutive daily injections. Half-revolutions of locomotor activity were recorded during seven measurement periods taken daily. During the third measurement period, from 1-3 hrs following injection, the methylphenidate group declined in locomotor activity over the first three days of drug administration."} {"id": "PMID:1257363", "title": "Amphetamine and the reward system: evidence for tolerance and post-drug depression.", "content": "Existing reports of tolerance to the behavioral effects of d-amphetamine are most parsimoniously interpreted as reflecting behavioral adaptation to the disruptive effects of the drug rather than physiological tolerance. The present study shows that physiological tolerance does develop to the facilitation of self-stimulation behavior which the drug produces. Rats were trained to bar-press for electrical stimulation of the medial forebrain bundle and tested for facilitation of responding following the administration of 0.25 or 0.50 mg/kg d-amphetamine. Testing was terminated for 4 days during which increasing doses (1.0-12.0 mg/kg) of the drug were given. 16 h after the last injection, the test doses (0.25 or 0.50 mg/kg) no longer produced facilitation of self-stimulation. In addition, testing on the following day with no further drug administration showed a depression of responding indicating depression of the sensitivity of the reward system of the brain.", "contents": "Amphetamine and the reward system: evidence for tolerance and post-drug depression. Existing reports of tolerance to the behavioral effects of d-amphetamine are most parsimoniously interpreted as reflecting behavioral adaptation to the disruptive effects of the drug rather than physiological tolerance. The present study shows that physiological tolerance does develop to the facilitation of self-stimulation behavior which the drug produces. Rats were trained to bar-press for electrical stimulation of the medial forebrain bundle and tested for facilitation of responding following the administration of 0.25 or 0.50 mg/kg d-amphetamine. Testing was terminated for 4 days during which increasing doses (1.0-12.0 mg/kg) of the drug were given. 16 h after the last injection, the test doses (0.25 or 0.50 mg/kg) no longer produced facilitation of self-stimulation. In addition, testing on the following day with no further drug administration showed a depression of responding indicating depression of the sensitivity of the reward system of the brain."} {"id": "PMID:1257364", "title": "Impaired development of tolerance to morphine analgesia in rats with hereditary diabetes insipidus.", "content": "Recently it was reported that vasopressin facilitates the development of resistance to the analgestic action of morphine. Therefore, the development of tolerance to daily administration of morphine-HCl (10 mg/kg i.p.) was studied in a series of trials on a hot plate using rats with hereditary diabetes insipidus (DI), which lack the ability to synthesize vasopressin. In contrast to heterozygous DI rats, who developed full tolerance after the fifth injection, homozygous DI rats showed a delayed development of tolerance. Substitution of HO-DI rats with either arginine-8-vasopressin (3 mug/rat, s.c. daily) or the endocrinologically inert fragment of vasopressin desglycinamide lysine-8-vasopressin (5 mug/100 g, s.c. daily) restored the impaired development of tolerance towards normal. The data support the notion that vasopressin is important to the development of tolerance to narcotic analgesics and that its mechanism of action is dissociated from its endocrine effect but rather resembles that of its known influence on memory consolidation.", "contents": "Impaired development of tolerance to morphine analgesia in rats with hereditary diabetes insipidus. Recently it was reported that vasopressin facilitates the development of resistance to the analgestic action of morphine. Therefore, the development of tolerance to daily administration of morphine-HCl (10 mg/kg i.p.) was studied in a series of trials on a hot plate using rats with hereditary diabetes insipidus (DI), which lack the ability to synthesize vasopressin. In contrast to heterozygous DI rats, who developed full tolerance after the fifth injection, homozygous DI rats showed a delayed development of tolerance. Substitution of HO-DI rats with either arginine-8-vasopressin (3 mug/rat, s.c. daily) or the endocrinologically inert fragment of vasopressin desglycinamide lysine-8-vasopressin (5 mug/100 g, s.c. daily) restored the impaired development of tolerance towards normal. The data support the notion that vasopressin is important to the development of tolerance to narcotic analgesics and that its mechanism of action is dissociated from its endocrine effect but rather resembles that of its known influence on memory consolidation."} {"id": "PMID:1257365", "title": "Memory performance after flurothyl treatment in rainbow trout.", "content": "Fingerling rainbow trout (N = 436) were trained in one trial with brief electric shock (2.0 V/cm) to suppress their spontaneous upstream swimming into a quiet well. Memory retention one day later was not influenced by the temperature at which they had been acclimated, trained and tested (10 degrees C, 15 degrees C or 20 degrees C). When exposed 4 min after training for 2 min, to a flurothyl solution (10, 25, 50, 100 or 200 mul/l) trout convulsed and overturned. The onset of overturn was concentration- and temperature-dependent. Flurothyl altered the one-day retention of avoidance behavior; low concentrations enhanced, whereas high concentrations impaired. Memory-enhancing low concentrations of flurothyl, applied after post-training amnesic treatment with carbon dioxide, reversed the carbon dioxide amnesia.", "contents": "Memory performance after flurothyl treatment in rainbow trout. Fingerling rainbow trout (N = 436) were trained in one trial with brief electric shock (2.0 V/cm) to suppress their spontaneous upstream swimming into a quiet well. Memory retention one day later was not influenced by the temperature at which they had been acclimated, trained and tested (10 degrees C, 15 degrees C or 20 degrees C). When exposed 4 min after training for 2 min, to a flurothyl solution (10, 25, 50, 100 or 200 mul/l) trout convulsed and overturned. The onset of overturn was concentration- and temperature-dependent. Flurothyl altered the one-day retention of avoidance behavior; low concentrations enhanced, whereas high concentrations impaired. Memory-enhancing low concentrations of flurothyl, applied after post-training amnesic treatment with carbon dioxide, reversed the carbon dioxide amnesia."} {"id": "PMID:1257366", "title": "A test of state dependency effects in marihuana intoxication for the learning of psychomotor tasks.", "content": "Cannabis cigarettes calibrated to deliver 7 mg delta9-THC were administered to experienced cannabis users and to novices in a 2 x 2 state-dependency learning design using psychomotor tasks. Subjects given four training sessions under marihuana performed no better on the fifth (test) session with the drug than those subjects who had trained in the non-drug condition and were tested in the drug condition. Cannabis-induced impairment in the performance of these tasks is such that prior training in the non-drug condition appears to confer no advantage to the subject. There was no evidence of state-dependency effects in psychomotor performance between drug and non-drug conditions.", "contents": "A test of state dependency effects in marihuana intoxication for the learning of psychomotor tasks. Cannabis cigarettes calibrated to deliver 7 mg delta9-THC were administered to experienced cannabis users and to novices in a 2 x 2 state-dependency learning design using psychomotor tasks. Subjects given four training sessions under marihuana performed no better on the fifth (test) session with the drug than those subjects who had trained in the non-drug condition and were tested in the drug condition. Cannabis-induced impairment in the performance of these tasks is such that prior training in the non-drug condition appears to confer no advantage to the subject. There was no evidence of state-dependency effects in psychomotor performance between drug and non-drug conditions."} {"id": "PMID:1257367", "title": "Autoradiographic studies on the distribution of 3H-2,3,4-trimethoxy-beta-phenylethylamine in the mouse.", "content": "The regional distribution of radioactivity was studied in the brain and in other organs of the mouse by light microscopic autoradiography after injection of 3H-2,3,4-trimethoxy-beta-phenylethylamine (2,3,4,-TMPEA), a nonhallucinogenic isomer of mescaline. The distribution patterns were compared with biochemical and autoradiographic results obtained after 3H-mescaline. Although 2,3,4-TMPEA is rapidly deaminated compared to mescaline its distribution pattern in the brain is similar to that of mescaline at 1 h after injection. However, contrary to mescaline the radioactive labeling becomes more and more homogenously distributed in the brain with tiem. The distribution patterns in kidney, pancreas, adrenal, and spinal ganglia were also different from those observed after application of 3H-mescaline.", "contents": "Autoradiographic studies on the distribution of 3H-2,3,4-trimethoxy-beta-phenylethylamine in the mouse. The regional distribution of radioactivity was studied in the brain and in other organs of the mouse by light microscopic autoradiography after injection of 3H-2,3,4-trimethoxy-beta-phenylethylamine (2,3,4,-TMPEA), a nonhallucinogenic isomer of mescaline. The distribution patterns were compared with biochemical and autoradiographic results obtained after 3H-mescaline. Although 2,3,4-TMPEA is rapidly deaminated compared to mescaline its distribution pattern in the brain is similar to that of mescaline at 1 h after injection. However, contrary to mescaline the radioactive labeling becomes more and more homogenously distributed in the brain with tiem. The distribution patterns in kidney, pancreas, adrenal, and spinal ganglia were also different from those observed after application of 3H-mescaline."} {"id": "PMID:1257368", "title": "Temporal parameters of d-amphetamine as a discriminative stimulus in the rat.", "content": "Three groups of rats were trained on a two-lever operant discrimination using d-amphetamine (0.8, 1.6 or 2.4 mg/kg) and saline as cues. Reinforcement of responding on one lever was associated with the drug and reinforcement on the other lever was associated with saline. Following acquisition, behavioral control was evaluated during 10-min extinction tests at 0, 15, 30, 60, 90, 120, 180 or 240 min after injection of drug or saline. Onset of the stimulus properties of d-amphetamine occurred within 10 min and maximal effects were attained by 15-30 min post-injection. Drug effects were minimal or absent 2-4 h after administration. The time course for all doses of d-amphetamine was identical when each group was tested iwth its respective training dose. When subjects were tested with doses other than their training dose, the time course of the drug effect varied as a function of training dose, test dose and time after injection.", "contents": "Temporal parameters of d-amphetamine as a discriminative stimulus in the rat. Three groups of rats were trained on a two-lever operant discrimination using d-amphetamine (0.8, 1.6 or 2.4 mg/kg) and saline as cues. Reinforcement of responding on one lever was associated with the drug and reinforcement on the other lever was associated with saline. Following acquisition, behavioral control was evaluated during 10-min extinction tests at 0, 15, 30, 60, 90, 120, 180 or 240 min after injection of drug or saline. Onset of the stimulus properties of d-amphetamine occurred within 10 min and maximal effects were attained by 15-30 min post-injection. Drug effects were minimal or absent 2-4 h after administration. The time course for all doses of d-amphetamine was identical when each group was tested iwth its respective training dose. When subjects were tested with doses other than their training dose, the time course of the drug effect varied as a function of training dose, test dose and time after injection."} {"id": "PMID:1257369", "title": "Pharmacological suppression of photically evoked after-discharges in rats: incremental dose, hippocampal EEG and behavioral activity correlates.", "content": "In subjects lightly restrained (Experiment I) pharmacological arousal via pilocarpine, physostigmine, or amphetamine administration, as compared to saline and methyl atropine treated controls, suppressed photically evoked after-discharge (PhAD) activity in visual cortex, while concomitantly inducing rhythmical slow-wave activity (RSA) in dorsal hippocampus. Incremental doses of amphetamine and pilocarpine correspondingly suppressed PhAD parameters in a dose-response fashion. While physostigmine treatment resulted in significant PhAD suppression, this effect could not be quantified in a dose-response manner. Incrementally increased cholinergic blockade via atropine administration also suppressed PhAD bursting yet simultaneously induced large amplitude irregular slow-wave activity (LIA) in dorsal hippocampus. When tested under identical conditions but in an unrestrained environment (Experiment II) PhADs were similarly suppressed with the concomitant induction of hippocampal patterns as specified in Experiment I; however, general ambulatory activity (grid-crossing) was differentially affected by the drugs. Amphetamine and atropine markedly enhanced while pilocarpine and physostigmine suppressed such activity. In both experiments, previously established PhAD-movement, PhAD-RSA-LIA, and RSA-LIA-movement relationships, occurring as hypothesized in amphetamine, methyl atropine, and saline treated animals, did not remain fully intact during cholinergic alteration.", "contents": "Pharmacological suppression of photically evoked after-discharges in rats: incremental dose, hippocampal EEG and behavioral activity correlates. In subjects lightly restrained (Experiment I) pharmacological arousal via pilocarpine, physostigmine, or amphetamine administration, as compared to saline and methyl atropine treated controls, suppressed photically evoked after-discharge (PhAD) activity in visual cortex, while concomitantly inducing rhythmical slow-wave activity (RSA) in dorsal hippocampus. Incremental doses of amphetamine and pilocarpine correspondingly suppressed PhAD parameters in a dose-response fashion. While physostigmine treatment resulted in significant PhAD suppression, this effect could not be quantified in a dose-response manner. Incrementally increased cholinergic blockade via atropine administration also suppressed PhAD bursting yet simultaneously induced large amplitude irregular slow-wave activity (LIA) in dorsal hippocampus. When tested under identical conditions but in an unrestrained environment (Experiment II) PhADs were similarly suppressed with the concomitant induction of hippocampal patterns as specified in Experiment I; however, general ambulatory activity (grid-crossing) was differentially affected by the drugs. Amphetamine and atropine markedly enhanced while pilocarpine and physostigmine suppressed such activity. In both experiments, previously established PhAD-movement, PhAD-RSA-LIA, and RSA-LIA-movement relationships, occurring as hypothesized in amphetamine, methyl atropine, and saline treated animals, did not remain fully intact during cholinergic alteration."} {"id": "PMID:1257370", "title": "Effect of cannabinoids on the abdominal constriction response in mice: within cannabinoid interactions.", "content": "After oral administration to mice, delta9-tetrahydrocannabinol (THC) and cannabinol (CBN) caused a dose-dependent suppression of the abdominal constriction response to formic acid. Cannabinol was 50 times less active than THC and cannabidiol (CBD) was without effect. The effects of THC and CBN were additive. CBD antagonised the antinociceptive effects of both THC and CBN in a dose-dependent manner.", "contents": "Effect of cannabinoids on the abdominal constriction response in mice: within cannabinoid interactions. After oral administration to mice, delta9-tetrahydrocannabinol (THC) and cannabinol (CBN) caused a dose-dependent suppression of the abdominal constriction response to formic acid. Cannabinol was 50 times less active than THC and cannabidiol (CBD) was without effect. The effects of THC and CBN were additive. CBD antagonised the antinociceptive effects of both THC and CBN in a dose-dependent manner."} {"id": "PMID:1257371", "title": "Piracetam-induced facilitation of interhemispheric transfer of visual information in rats.", "content": "The effect of Piracetam (UCB 6215, 2-pyrrolidoneacetamide) on learning mediated by transcommissural information flow was studied in hooded rats. Acquisition of monocular pattern discrimination was faster in drug-treated rats (100 mg/kg, 30 min before training) than in untreated controls. Subsequent relearning with one hemisphere functionally eliminated by cortical spreading depression showed that the strength of the primary engram formed under Piracetam in the hemisphere contralateral to the trained eye remained unaffected but that the secondary trace (in the ipsilateral hemisphere) was considerably improved and almost equalled the primary one (savings increased from 20-30% to 50-60%). Learning with uncrossed optic fibers was unaffected by the drug. Interhemispheric transfer of lateralized visual engrams acquired during functional hemidecortication was facilitated by Piracetam administration preceding the five transfer trials performed with the untrained eye open (imperative transfer). Piracetam was ineffective when the trained eye was open during transfer trials (facultative transfer). After a visual engram had been lateralized by 5 days of monocular overtraining, Piracetam facilitated formation of the secondary engram induced by 3 interocular transfer trials. It is concluded that Piracetam enhances transcommissural encoding mechanisms activated in the initial stage of monocular learning and in some forms of interhemispheric transfer, but does not affect the transcommissural readout. This effect is interpreted as a special case of the Piracetam-induced facilitation of the phylogenetically old mechanisms of redundant information storage which improve liminal or subnormal learning.", "contents": "Piracetam-induced facilitation of interhemispheric transfer of visual information in rats. The effect of Piracetam (UCB 6215, 2-pyrrolidoneacetamide) on learning mediated by transcommissural information flow was studied in hooded rats. Acquisition of monocular pattern discrimination was faster in drug-treated rats (100 mg/kg, 30 min before training) than in untreated controls. Subsequent relearning with one hemisphere functionally eliminated by cortical spreading depression showed that the strength of the primary engram formed under Piracetam in the hemisphere contralateral to the trained eye remained unaffected but that the secondary trace (in the ipsilateral hemisphere) was considerably improved and almost equalled the primary one (savings increased from 20-30% to 50-60%). Learning with uncrossed optic fibers was unaffected by the drug. Interhemispheric transfer of lateralized visual engrams acquired during functional hemidecortication was facilitated by Piracetam administration preceding the five transfer trials performed with the untrained eye open (imperative transfer). Piracetam was ineffective when the trained eye was open during transfer trials (facultative transfer). After a visual engram had been lateralized by 5 days of monocular overtraining, Piracetam facilitated formation of the secondary engram induced by 3 interocular transfer trials. It is concluded that Piracetam enhances transcommissural encoding mechanisms activated in the initial stage of monocular learning and in some forms of interhemispheric transfer, but does not affect the transcommissural readout. This effect is interpreted as a special case of the Piracetam-induced facilitation of the phylogenetically old mechanisms of redundant information storage which improve liminal or subnormal learning."} {"id": "PMID:1257381", "title": "Physiological concomitants (I131 uptake) of field dependence.", "content": "Radioactive iodine uptake levels of two matched groups 11 field dependent and 11 field independent male euthyroid medical students were compared at the 7th, 24th, and 48th hr and at the 7th day. Significantly higher levels were observed in the field dependent group at all points except the 48th hr. These findings may reflect individual differences in adaptive psychoendocrine functioning.", "contents": "Physiological concomitants (I131 uptake) of field dependence. Radioactive iodine uptake levels of two matched groups 11 field dependent and 11 field independent male euthyroid medical students were compared at the 7th, 24th, and 48th hr and at the 7th day. Significantly higher levels were observed in the field dependent group at all points except the 48th hr. These findings may reflect individual differences in adaptive psychoendocrine functioning."} {"id": "PMID:1257383", "title": "The magnitude of premenstrual anxiety and depression.", "content": "The magnitude of premenstrual mood changes in 50 parous adult women between the ages of 30 and 45 was assessed using standardized measures of depression and anxiety. Premenstrual test scores were compared with those obtained during the intermenstrual phase of the cycle and with normative data. Premenstrual state anxiety and depression mean scores were significantly higher than those obtained midcycle, but were much lower than those of patients with psychiatric disorders. Trait anxiety scores were low and were not significantly correlated with premenstrual depression and anxiety scores.", "contents": "The magnitude of premenstrual anxiety and depression. The magnitude of premenstrual mood changes in 50 parous adult women between the ages of 30 and 45 was assessed using standardized measures of depression and anxiety. Premenstrual test scores were compared with those obtained during the intermenstrual phase of the cycle and with normative data. Premenstrual state anxiety and depression mean scores were significantly higher than those obtained midcycle, but were much lower than those of patients with psychiatric disorders. Trait anxiety scores were low and were not significantly correlated with premenstrual depression and anxiety scores."} {"id": "PMID:1257380", "title": "Tetrahydrocortisol/tetrahydrocortisone ratio (H4F/H4E) as an indicator of depressive feelings.", "content": "Tetrahydrocortisol (H4F) and tetrahydrocortisone (H4E) were determined for a group of 15 depressed patients and 25 normal controls following the administration of cortisol-4-C14. The ratio, H4F/H4E, was significantly greater for the depressed patients than for the normal controls (P less than 0.001), although the sum of the two metabolites, H4F + H4E, was not significantly different. Three of four objective test measures of depressive feelings likewise discriminated between the two groups. All four depression measures correlated significantly with the H4F/H4E ratio at the 0.01 level or better. It is suggested that the data of the present report and those of Zumoff et al. (J Clin Endocrinol Metab 39:1120, 1974) may be explained by the paradigm: depressive feelings leads to reduced thyroid function leads to elevated H4F/H4E ratio.", "contents": "Tetrahydrocortisol/tetrahydrocortisone ratio (H4F/H4E) as an indicator of depressive feelings. Tetrahydrocortisol (H4F) and tetrahydrocortisone (H4E) were determined for a group of 15 depressed patients and 25 normal controls following the administration of cortisol-4-C14. The ratio, H4F/H4E, was significantly greater for the depressed patients than for the normal controls (P less than 0.001), although the sum of the two metabolites, H4F + H4E, was not significantly different. Three of four objective test measures of depressive feelings likewise discriminated between the two groups. All four depression measures correlated significantly with the H4F/H4E ratio at the 0.01 level or better. It is suggested that the data of the present report and those of Zumoff et al. (J Clin Endocrinol Metab 39:1120, 1974) may be explained by the paradigm: depressive feelings leads to reduced thyroid function leads to elevated H4F/H4E ratio."} {"id": "PMID:1257384", "title": "A consultation-liaison psychiatry clinical clerkship.", "content": "Toward the goal of increasing the relevance of clinical psychiatry to the future practice of medicine, a full-time psychiatry clerkship has been developed on the Consultation-Liaison Psychiatry Service at the University of Vermont. This new Psychiatry Clinical clerkship was begun on a pilot basis in January, 1973, and made fully operational in January, 1974. It uses the problem oriented medical record system and the audit of student performance as basic instructional tools. A description of the background or curricular matrix of the Consultation-Liaison Psychiatry Clinical Clerkship (CLPCC) is followed by an outline of the rotation's goals, and evaluation and educational strategies as developed over 2 years. Certain performance outcomes are reported for the 1 year of full operation. These outcomes are parameters of student performance on several standardized measures applied to all Psychiatry Clerkship students. The CLPCC students seem to be at least as adequate as students on all other clerkship rotations, in terms of their knowledge of psychopharmacology, their use of the Problem Oriented Record, their ability to assess psychosocial problems, and their ability to define a psychosocial treatment plan. Further, the CLPCC students are statistically significantly more positive about their rotation as an educational experience compared with students on other psychiatry rotations. While further evaluation measures are planned to compare the CLPCC students with those who have had one of the several traditional clinical clerkship experiences in psychiatry, our experience to date would indicate that the CLPCC is a viable alternative to traditional clerkships on psychiatric services and one that may enable a greater application of psychiatric principles to the practice of medicine.", "contents": "A consultation-liaison psychiatry clinical clerkship. Toward the goal of increasing the relevance of clinical psychiatry to the future practice of medicine, a full-time psychiatry clerkship has been developed on the Consultation-Liaison Psychiatry Service at the University of Vermont. This new Psychiatry Clinical clerkship was begun on a pilot basis in January, 1973, and made fully operational in January, 1974. It uses the problem oriented medical record system and the audit of student performance as basic instructional tools. A description of the background or curricular matrix of the Consultation-Liaison Psychiatry Clinical Clerkship (CLPCC) is followed by an outline of the rotation's goals, and evaluation and educational strategies as developed over 2 years. Certain performance outcomes are reported for the 1 year of full operation. These outcomes are parameters of student performance on several standardized measures applied to all Psychiatry Clerkship students. The CLPCC students seem to be at least as adequate as students on all other clerkship rotations, in terms of their knowledge of psychopharmacology, their use of the Problem Oriented Record, their ability to assess psychosocial problems, and their ability to define a psychosocial treatment plan. Further, the CLPCC students are statistically significantly more positive about their rotation as an educational experience compared with students on other psychiatry rotations. While further evaluation measures are planned to compare the CLPCC students with those who have had one of the several traditional clinical clerkship experiences in psychiatry, our experience to date would indicate that the CLPCC is a viable alternative to traditional clerkships on psychiatric services and one that may enable a greater application of psychiatric principles to the practice of medicine."} {"id": "PMID:1257382", "title": "The effect of biofeedback training on respiratory resistance of asthmatic children.", "content": "In a pilot study four children with severe asthma were trained to lower their respiratory resistance by means of biofeedback training techniques. Total respiratory resistance measured continuously by the forced oscillation method was used as the feedback signal. Each child demonstrated lowered respiratory resistance after most sessions. Results were comparable with the improvement seen after bronchodilator inhalation therapy. A nonasthmatic child demonstrated no significant changes of respiratory resistance after using the same techniques. Arguments are presented in support of the hypothesis that changes in total respiratory resistance were primarily due to changes in lower airway resistance. Lowering of airway resistance in asthmatic children by use of biofeedback appears possible; its promise calls for further clinical evaluation.", "contents": "The effect of biofeedback training on respiratory resistance of asthmatic children. In a pilot study four children with severe asthma were trained to lower their respiratory resistance by means of biofeedback training techniques. Total respiratory resistance measured continuously by the forced oscillation method was used as the feedback signal. Each child demonstrated lowered respiratory resistance after most sessions. Results were comparable with the improvement seen after bronchodilator inhalation therapy. A nonasthmatic child demonstrated no significant changes of respiratory resistance after using the same techniques. Arguments are presented in support of the hypothesis that changes in total respiratory resistance were primarily due to changes in lower airway resistance. Lowering of airway resistance in asthmatic children by use of biofeedback appears possible; its promise calls for further clinical evaluation."} {"id": "PMID:1257398", "title": "The haematology of hypothyroidism.", "content": "In an unselected series of 202 patients with hypothyroidism anaemia was present on diagnosis in 39 of 172 women and 14 of 30 men. Microcytic anaemia was present in only nine patients in the entire series. The average of the mean corpuscular volume (MCV) of all the patients was 90 fl. Fifty-three of 118 patients who were studied in detail had normal serum concentrations of vitamin B12, folic acid and iron. The haemoglobin was low in 13 of these 53 patients and rose on treatment with thyroxine alone. The MCV exceeded 90 fl in 29 of these 53 patients and in three it was greater than 100 fl. The MCV invariably fell on treatment with thyroxine even if the initial value was within the normal range. Nine of this group of 53 patients had both anaemia and an increased MCV--the macrocytic anaemia of hypothyroidism. A minor degree of anisocytosis of the red blood cells, which was reduced by treatment with thyroxine, was also demonstrated. Acanthocytes were present in the blood films of 32 out of 172 patients but in only five did the abnormal cells comprise more than 0-5 per cent of the red cell population. The incidence of new cases of pernicious anaemia diagnosed concurrently with the hypothyroidism in the carefully studied group of 118 patients was 8-5 per cent. The MCV of hypothyroid patients with low levels of vitamin B12 was often no greater than in patients with uncomplicated hypothyroidism. The MCV is not therefore a useful discriminant in the diagnosis of pernicious anaemia in hypothyroidism. The serum iron concentration was less than 12 mumol/1 in 60 out of 118 patients. The total iron binding capacity of the serum was increased in only 21 of these 60 patients. In 42 hypothyroid patients the low serum iron concentration was not associated with low levels of either vitamin B12 or folate and of these patients 22 were anaemic. Despite the very low percentage saturation of the iron binding capacity in all of these patients with a low serum iron, a lack of iron did not seem to be the usual determinant of anaemia when it occurred.", "contents": "The haematology of hypothyroidism. In an unselected series of 202 patients with hypothyroidism anaemia was present on diagnosis in 39 of 172 women and 14 of 30 men. Microcytic anaemia was present in only nine patients in the entire series. The average of the mean corpuscular volume (MCV) of all the patients was 90 fl. Fifty-three of 118 patients who were studied in detail had normal serum concentrations of vitamin B12, folic acid and iron. The haemoglobin was low in 13 of these 53 patients and rose on treatment with thyroxine alone. The MCV exceeded 90 fl in 29 of these 53 patients and in three it was greater than 100 fl. The MCV invariably fell on treatment with thyroxine even if the initial value was within the normal range. Nine of this group of 53 patients had both anaemia and an increased MCV--the macrocytic anaemia of hypothyroidism. A minor degree of anisocytosis of the red blood cells, which was reduced by treatment with thyroxine, was also demonstrated. Acanthocytes were present in the blood films of 32 out of 172 patients but in only five did the abnormal cells comprise more than 0-5 per cent of the red cell population. The incidence of new cases of pernicious anaemia diagnosed concurrently with the hypothyroidism in the carefully studied group of 118 patients was 8-5 per cent. The MCV of hypothyroid patients with low levels of vitamin B12 was often no greater than in patients with uncomplicated hypothyroidism. The MCV is not therefore a useful discriminant in the diagnosis of pernicious anaemia in hypothyroidism. The serum iron concentration was less than 12 mumol/1 in 60 out of 118 patients. The total iron binding capacity of the serum was increased in only 21 of these 60 patients. In 42 hypothyroid patients the low serum iron concentration was not associated with low levels of either vitamin B12 or folate and of these patients 22 were anaemic. Despite the very low percentage saturation of the iron binding capacity in all of these patients with a low serum iron, a lack of iron did not seem to be the usual determinant of anaemia when it occurred."} {"id": "PMID:1257399", "title": "Idiopathic oedema of women. A clinical and investigative study.", "content": "A clinical and investigative study is reported of 19 patients with 'idiopathic oedema of women'. The resons for defining this as a specific syndrome unrelated to the menstrual cycle are given, and the clinical features reviewed. During a forced water diuresis the flow and composition of the urine and the plasma volume were studied on tilting from the supine to the upright position seven premenopausal and four postmenopausal patients with this disorder. No differences were found in the results obtained in the follicular and luteal phases of the menstrual cycle or in the pre- and post-menopausal patients. The reductions in urinary volume and electrolyte excretion on upright tilting were greater than those observed under similar circumstances during the luteal phase of the menstrual cycle in normal female controls, and attributed to increased proximal renal tubular reabsorption. The rate of loss of isotopically labelled albumin from the intravascular compartment was greater in patients with idiopathic oedema than in control subjects. A reduction in blood volume on tilting occurred in control subjects and patients with idiopathic oedema, but was greater in the latter; and the larger the fall, the greater were the reductions in urinary flow and electrolyte excretion. The effect of administering 9-alpha-fluorohydrocortisone was studied in nine patients with idiopathic oedema. One patient failed to 'escape' from the sodium-retaining action of this mineralocorticoid and developed pulmonary oedema; the others 'escaped' normally. The pathophysiological disturbance in this condition is related to increased loss of fluid from the vascular compartment but the precise aetiological mechanism remains unknown.", "contents": "Idiopathic oedema of women. A clinical and investigative study. A clinical and investigative study is reported of 19 patients with 'idiopathic oedema of women'. The resons for defining this as a specific syndrome unrelated to the menstrual cycle are given, and the clinical features reviewed. During a forced water diuresis the flow and composition of the urine and the plasma volume were studied on tilting from the supine to the upright position seven premenopausal and four postmenopausal patients with this disorder. No differences were found in the results obtained in the follicular and luteal phases of the menstrual cycle or in the pre- and post-menopausal patients. The reductions in urinary volume and electrolyte excretion on upright tilting were greater than those observed under similar circumstances during the luteal phase of the menstrual cycle in normal female controls, and attributed to increased proximal renal tubular reabsorption. The rate of loss of isotopically labelled albumin from the intravascular compartment was greater in patients with idiopathic oedema than in control subjects. A reduction in blood volume on tilting occurred in control subjects and patients with idiopathic oedema, but was greater in the latter; and the larger the fall, the greater were the reductions in urinary flow and electrolyte excretion. The effect of administering 9-alpha-fluorohydrocortisone was studied in nine patients with idiopathic oedema. One patient failed to 'escape' from the sodium-retaining action of this mineralocorticoid and developed pulmonary oedema; the others 'escaped' normally. The pathophysiological disturbance in this condition is related to increased loss of fluid from the vascular compartment but the precise aetiological mechanism remains unknown."} {"id": "PMID:1257400", "title": "Intestinal lymphangiectasia: the variability of presentation. A study of five cases.", "content": "Five patients with intestinal lymphangiectasia are described. They all had evidence of protein-loss from the gut but this was of a variable degree. In four patients the diagnosis was first suggested by the appearances of jejunal biopsy. The factors influencing presentation are discussed as are the possible co-existence of other gastronitestinal disorders with this congenital abnormality. It seems likely that the condition is commoner than hitherto believed.", "contents": "Intestinal lymphangiectasia: the variability of presentation. A study of five cases. Five patients with intestinal lymphangiectasia are described. They all had evidence of protein-loss from the gut but this was of a variable degree. In four patients the diagnosis was first suggested by the appearances of jejunal biopsy. The factors influencing presentation are discussed as are the possible co-existence of other gastronitestinal disorders with this congenital abnormality. It seems likely that the condition is commoner than hitherto believed."} {"id": "PMID:1257401", "title": "Serum ionized calcium and parathyroid hormone in renal stone disease.", "content": "Serum ionized calcium was shown to be significantly elevated in a group of twenty-eight subjects with idiopathic hypercalciuria in whom the mean total serum calcium concentration was within normal limits. Measurement of parathyroid hormone levels confirmed that elevated values are suppressible by infusion of calcium. Ten subjects with simultaneous elevation of serum ionized calcium and parathormone levels above 3 S.D. of normal were referred for neck exploration, and a parathyroid adenoma was found and removed in nine. Significant decreases to normal values of serum ionized calcium and parathormone levels of urine and calcium excretion were documented some weeks following operation. The results conflict with both the alimentary calcium hyperabsorption theory and the renal calcium leak theory of the aetiology of idiopathic hypercalciuria, and support the possibility that idiopathic hypercalciuria in many cases represents an early or mild form of 'normocalcaemic' primary hyperparathyroidism.", "contents": "Serum ionized calcium and parathyroid hormone in renal stone disease. Serum ionized calcium was shown to be significantly elevated in a group of twenty-eight subjects with idiopathic hypercalciuria in whom the mean total serum calcium concentration was within normal limits. Measurement of parathyroid hormone levels confirmed that elevated values are suppressible by infusion of calcium. Ten subjects with simultaneous elevation of serum ionized calcium and parathormone levels above 3 S.D. of normal were referred for neck exploration, and a parathyroid adenoma was found and removed in nine. Significant decreases to normal values of serum ionized calcium and parathormone levels of urine and calcium excretion were documented some weeks following operation. The results conflict with both the alimentary calcium hyperabsorption theory and the renal calcium leak theory of the aetiology of idiopathic hypercalciuria, and support the possibility that idiopathic hypercalciuria in many cases represents an early or mild form of 'normocalcaemic' primary hyperparathyroidism."} {"id": "PMID:1257425", "title": "[Semimalignant skeletal tumors (author's transl)].", "content": "Osteoclastoma, chondroma and chordoma are tumors of the skeletal system which have some common features: in spite of benign histological findings their clinical course is that of a malignant neoplasm. They show an aggressive growth and a high rate of recurrencies mainly when the initial therapeutic procedure was insufficient. Osteolysis is the principal sign in the roentgenogram. However, there is no correlation between the roentgenogram and the dignity of the tumor. The best therapy is the radical operation. A good cooperation between surgeon, radiologist and surgical pathologist is very important for the prognosis of patients with this lesion.", "contents": "[Semimalignant skeletal tumors (author's transl)]. Osteoclastoma, chondroma and chordoma are tumors of the skeletal system which have some common features: in spite of benign histological findings their clinical course is that of a malignant neoplasm. They show an aggressive growth and a high rate of recurrencies mainly when the initial therapeutic procedure was insufficient. Osteolysis is the principal sign in the roentgenogram. However, there is no correlation between the roentgenogram and the dignity of the tumor. The best therapy is the radical operation. A good cooperation between surgeon, radiologist and surgical pathologist is very important for the prognosis of patients with this lesion."} {"id": "PMID:1257426", "title": "[Eosinophilic granuloma of the bone in adults (author's transl)].", "content": "Eosinophilic granuloma of the bone shows a characteristic age distribution with an incidence of 75% in children. According to our observations, however, its occurrence in adults is not as rare as one should expect from the number of cases reported in the literature. The clinical and radiologic diagnosis can be established in many cases if the possibility of an eosinophilic granuloma is considered and certain criteria are taken in consideration. Solitary osteolytic changes should be biopsied early in order to avoid unnecessary and expensive examinations. The X-ray signs which can lead to the diagnosis are discussed and illustrated, and 7 cases of eosinophilic granuloma in adults are presented.", "contents": "[Eosinophilic granuloma of the bone in adults (author's transl)]. Eosinophilic granuloma of the bone shows a characteristic age distribution with an incidence of 75% in children. According to our observations, however, its occurrence in adults is not as rare as one should expect from the number of cases reported in the literature. The clinical and radiologic diagnosis can be established in many cases if the possibility of an eosinophilic granuloma is considered and certain criteria are taken in consideration. Solitary osteolytic changes should be biopsied early in order to avoid unnecessary and expensive examinations. The X-ray signs which can lead to the diagnosis are discussed and illustrated, and 7 cases of eosinophilic granuloma in adults are presented."} {"id": "PMID:1257427", "title": "[Recent progress in morphology and diagnosis of bone diseases and bone tumors (author's transl)].", "content": "1. Bone structure is shaped by a specialized bone cell system comprising osteoblasts, osteocytes and osteoclasts. --2. The function of this bone cell system is impaired by metabolic bone disease altering bone structure, bone mass and mineral content. --3. In metabolic bone disease a striking improvement in morphologic diagnosis could be obtained recently using undecalcified preparations of bone tissue as well as histomorphometric methods. --4. For exact diagnosis and successful therapy of bone tumors interdisciplinary cooperation is mandatory. The advantages of modern morphologic methods are proven helpful in diagnosing benign and malignant bone tumors.", "contents": "[Recent progress in morphology and diagnosis of bone diseases and bone tumors (author's transl)]. 1. Bone structure is shaped by a specialized bone cell system comprising osteoblasts, osteocytes and osteoclasts. --2. The function of this bone cell system is impaired by metabolic bone disease altering bone structure, bone mass and mineral content. --3. In metabolic bone disease a striking improvement in morphologic diagnosis could be obtained recently using undecalcified preparations of bone tissue as well as histomorphometric methods. --4. For exact diagnosis and successful therapy of bone tumors interdisciplinary cooperation is mandatory. The advantages of modern morphologic methods are proven helpful in diagnosing benign and malignant bone tumors."} {"id": "PMID:1257428", "title": "[A new theory of the etiology of osteoporosis (author's transl)].", "content": "A new theory of the etiology of osteoporosis--inaugurated by the author and developed in cooperation with Fricke--is step by step elaborated and explained. Alteration of the bone marrow is observed simultaneonly with osteoporosis--caused by reduced blood flow in bone and bone marrow, and promoted by reduced muscle work, i.c. inactivity, influencing blood circulation in bone and bone marrow. Alteration of statics and vertebral bodies resulting from bone atrophy and reduced muscular force are newly interpreted by a new theory capabilities of radiological osteoporosis-diagnostis are preceding.", "contents": "[A new theory of the etiology of osteoporosis (author's transl)]. A new theory of the etiology of osteoporosis--inaugurated by the author and developed in cooperation with Fricke--is step by step elaborated and explained. Alteration of the bone marrow is observed simultaneonly with osteoporosis--caused by reduced blood flow in bone and bone marrow, and promoted by reduced muscle work, i.c. inactivity, influencing blood circulation in bone and bone marrow. Alteration of statics and vertebral bodies resulting from bone atrophy and reduced muscular force are newly interpreted by a new theory capabilities of radiological osteoporosis-diagnostis are preceding."} {"id": "PMID:1257429", "title": "[Synovectomy in rheumatoid arthritis of the knee, radiologic investigations (author's transl)].", "content": "Pathologic and radiologic investigations of rheumatoid arthritis are compared with regard to their development. Radiologic demonstration of several cases prior to and following synovectomy shows improvement as well as exacerbation of the disease. An increasing mineral content signifies an improvement of the bone lesion. The mineral content depends on reduction of inflammatory activity, increasing motility, and postoperative discontinuation of cortisone therapy. In some cases various lesions at the border line between bone and cartilage as blurring, notching and destructions are disappearing. Reduction of cartilage accompanied with narrowing of the joint spaces will subside postoperatively, too. We have to suppose a regeneration of cartilage under increasing physical strain by functional stimulation. Following synovectomy the structure of subcartilage spongiosa becomes more organized as a sign of regression of inflammatory activity, improved motility and load capacity. Following synovectomy, exacerbation of radiologic symptoms occur mainly in advanced stages of rheumatoid arthritis. We may often see progression of secondary osteoarthritis existing preoperatively in contrast to clinical recovery. The increasing load capacity may cause an identation of the articular surface in cases of extreme osteoporosis. This might result in a false position. These lesions might necessitate further surgical treatment as possibly total joint prosthesis. Following synovectomy in rheumatoid arthritis of the knee, dissolving radiologic symptoms in addition to improvement of the clinical picture may be observed. The poor results of synovectomy in advanced rheumatoid arthritis favours the of early synovectomy during the proliferative and destructive stage of the disease.", "contents": "[Synovectomy in rheumatoid arthritis of the knee, radiologic investigations (author's transl)]. Pathologic and radiologic investigations of rheumatoid arthritis are compared with regard to their development. Radiologic demonstration of several cases prior to and following synovectomy shows improvement as well as exacerbation of the disease. An increasing mineral content signifies an improvement of the bone lesion. The mineral content depends on reduction of inflammatory activity, increasing motility, and postoperative discontinuation of cortisone therapy. In some cases various lesions at the border line between bone and cartilage as blurring, notching and destructions are disappearing. Reduction of cartilage accompanied with narrowing of the joint spaces will subside postoperatively, too. We have to suppose a regeneration of cartilage under increasing physical strain by functional stimulation. Following synovectomy the structure of subcartilage spongiosa becomes more organized as a sign of regression of inflammatory activity, improved motility and load capacity. Following synovectomy, exacerbation of radiologic symptoms occur mainly in advanced stages of rheumatoid arthritis. We may often see progression of secondary osteoarthritis existing preoperatively in contrast to clinical recovery. The increasing load capacity may cause an identation of the articular surface in cases of extreme osteoporosis. This might result in a false position. These lesions might necessitate further surgical treatment as possibly total joint prosthesis. Following synovectomy in rheumatoid arthritis of the knee, dissolving radiologic symptoms in addition to improvement of the clinical picture may be observed. The poor results of synovectomy in advanced rheumatoid arthritis favours the of early synovectomy during the proliferative and destructive stage of the disease."} {"id": "PMID:1257430", "title": "[Xeroradiography and its value in the diagnosis of chondrocalcinosis (author's transl)].", "content": "Conventional x-ray and xeroradiographic technique were compared in a modified blind study in order to evaluate its efficiency to detect calcifications of the cartilage. Using both techniques knees, hands, and pelvic joints were examined in 16 patients with proven chondrocalcinosis. Three different radiologists evaluated radiological films and xeroradiograms independently. Their results were classified in correct, false negative, and false positive groups. All examiners achieved the best results with xeroradiography. Due to special characteristic features in xeroradiography even fine calcifications were recognized in most cases. By this method the \"false negative\" results were reduced to almost zero. On the other hand, the twenty percent \"false positive\" results in conventional radiological technique was eliminated by xeroradiography.", "contents": "[Xeroradiography and its value in the diagnosis of chondrocalcinosis (author's transl)]. Conventional x-ray and xeroradiographic technique were compared in a modified blind study in order to evaluate its efficiency to detect calcifications of the cartilage. Using both techniques knees, hands, and pelvic joints were examined in 16 patients with proven chondrocalcinosis. Three different radiologists evaluated radiological films and xeroradiograms independently. Their results were classified in correct, false negative, and false positive groups. All examiners achieved the best results with xeroradiography. Due to special characteristic features in xeroradiography even fine calcifications were recognized in most cases. By this method the \"false negative\" results were reduced to almost zero. On the other hand, the twenty percent \"false positive\" results in conventional radiological technique was eliminated by xeroradiography."} {"id": "PMID:1257431", "title": "Equipment vibration and radiographic image resolution.", "content": "Accelerometer transducers were employed to detect linear vibratory motions in various radiographic equipment during film exposure. Vibratory displacements sufficient to degrade the image were found in several spot-film devices and Bucky drawers. Other potential sources of image degradation are discussed.", "contents": "Equipment vibration and radiographic image resolution. Accelerometer transducers were employed to detect linear vibratory motions in various radiographic equipment during film exposure. Vibratory displacements sufficient to degrade the image were found in several spot-film devices and Bucky drawers. Other potential sources of image degradation are discussed."} {"id": "PMID:1257432", "title": "Experience with the AURA free-text documentation system.", "content": "AURA is a free-text system designed to facilitate automatic documentation of radiological reports, with the goal of making the information in the reports accessible for case location, feedback, and statistical evaluation without changing the regular routine of the radiologist. A simple interactive search language makes retrieval easy. Search criteria can be formulated in medical terms and do not require programming ability.", "contents": "Experience with the AURA free-text documentation system. AURA is a free-text system designed to facilitate automatic documentation of radiological reports, with the goal of making the information in the reports accessible for case location, feedback, and statistical evaluation without changing the regular routine of the radiologist. A simple interactive search language makes retrieval easy. Search criteria can be formulated in medical terms and do not require programming ability."} {"id": "PMID:1257433", "title": "Angiographic findings in recurrent meningioma.", "content": "Of 147 patients who underwent radical surgery for intracranial meningioma, 25 (17%) had symptomatic recurrence requiring further surgery. Correlation between histological and angiographic findings of recurrent meningioma was poor. Following extirpation of feeding meningeal vessels in convexity meningiomas, the principal blood supply was usually from the anterior, middle, and/or posterior cerebral arteries. The angiographic appearance was that of a \"tree-root\" or \"sunburst\" pattern, indicating neoplastic invasion of the pia mater and/or underlying brain tissue. Polytomography, selective cerebral angiography, and radionuclide imaging of the brain are often necessary to detect early recurrent meningiomas. Computed tomography appears to be an innocuous and accurate method of diagnosing recurrent tumor, especially when the bone is not involved.", "contents": "Angiographic findings in recurrent meningioma. Of 147 patients who underwent radical surgery for intracranial meningioma, 25 (17%) had symptomatic recurrence requiring further surgery. Correlation between histological and angiographic findings of recurrent meningioma was poor. Following extirpation of feeding meningeal vessels in convexity meningiomas, the principal blood supply was usually from the anterior, middle, and/or posterior cerebral arteries. The angiographic appearance was that of a \"tree-root\" or \"sunburst\" pattern, indicating neoplastic invasion of the pia mater and/or underlying brain tissue. Polytomography, selective cerebral angiography, and radionuclide imaging of the brain are often necessary to detect early recurrent meningiomas. Computed tomography appears to be an innocuous and accurate method of diagnosing recurrent tumor, especially when the bone is not involved."} {"id": "PMID:1257434", "title": "Intracerebral venous angioma.", "content": "Intracerebral venous angioma is a rare congenital vascular malformation of the brain. Three cases are reported, all of which had strikingly similar angiographic findings in the venous phase, viz., a local network of small medullary veins which converge centrally into a single large venous channel which courses transcerebrally to reach the superficial venous system. No gross abnormalities are seen in the arterial phase with the usual techniques. However, magnification delineated enlarged arterial branches supplying the periphery of the malformation in 2 of the 3 cases. A poorly marginated homogeneous blush and early filling of the draining veins were also seen in these 2 patients. The findings in the venous phase agree with those described in previous isolated case reports and appear to be highly suggestive of this rare malformation.", "contents": "Intracerebral venous angioma. Intracerebral venous angioma is a rare congenital vascular malformation of the brain. Three cases are reported, all of which had strikingly similar angiographic findings in the venous phase, viz., a local network of small medullary veins which converge centrally into a single large venous channel which courses transcerebrally to reach the superficial venous system. No gross abnormalities are seen in the arterial phase with the usual techniques. However, magnification delineated enlarged arterial branches supplying the periphery of the malformation in 2 of the 3 cases. A poorly marginated homogeneous blush and early filling of the draining veins were also seen in these 2 patients. The findings in the venous phase agree with those described in previous isolated case reports and appear to be highly suggestive of this rare malformation."} {"id": "PMID:1257435", "title": "Adhesive arachnoiditis after lumbar radiculography with Dimer-X and Depo-Medrol.", "content": "Lumbar radiculographs were obtained in 252 patients with suspected disk herniation. Fifteen patients who underwent previous radiculography with Dimer-X plus Depo-Medrol exhibited adhesive arachnoiditis. This was not observed in 6 patients who received Dimer-X alone. No positive correlation between radiological diagnosis of adhesive arachnoiditis and clinical symptoms can be demonstrated. The authors suggest that steroids not be used intrathecally in combination with water-soluble contrast media.", "contents": "Adhesive arachnoiditis after lumbar radiculography with Dimer-X and Depo-Medrol. Lumbar radiculographs were obtained in 252 patients with suspected disk herniation. Fifteen patients who underwent previous radiculography with Dimer-X plus Depo-Medrol exhibited adhesive arachnoiditis. This was not observed in 6 patients who received Dimer-X alone. No positive correlation between radiological diagnosis of adhesive arachnoiditis and clinical symptoms can be demonstrated. The authors suggest that steroids not be used intrathecally in combination with water-soluble contrast media."} {"id": "PMID:1257436", "title": "Comparative assessment of scintillation camera performance.", "content": "The performance characteristics of 5 scintillation cameras were compared: Searle 19, Searle 37, Ohio Nuclear, Picker 2C and Toshiba GCA 202. Inherent characteristics including spatial resolution, field uniformity and distortion, energy resolution, count-rate capability and paralyzing time were measured. Extrinsic characteristics such as spatial resolution with emission tests and sensitivity with high resolution, low energy collimators also were measured. The Ohio Nuclear camera gave the best results for most of the parameters studied, followed by Searle 37 PMT, Searle 19 PMT, Picker, and Toshiba. The size of the crystal must also be a criterion for choosing a camera.", "contents": "Comparative assessment of scintillation camera performance. The performance characteristics of 5 scintillation cameras were compared: Searle 19, Searle 37, Ohio Nuclear, Picker 2C and Toshiba GCA 202. Inherent characteristics including spatial resolution, field uniformity and distortion, energy resolution, count-rate capability and paralyzing time were measured. Extrinsic characteristics such as spatial resolution with emission tests and sensitivity with high resolution, low energy collimators also were measured. The Ohio Nuclear camera gave the best results for most of the parameters studied, followed by Searle 37 PMT, Searle 19 PMT, Picker, and Toshiba. The size of the crystal must also be a criterion for choosing a camera."} {"id": "PMID:1257437", "title": "The accuracy of 111InCl3 as a bone marrow scanning agent.", "content": "The number of normal cellular elements present in bone marrow biopsies was compared to the extent of uptake at corresponding sites on 111InCl3 bone marrow scans in 87 patients with malignant lymphoma. Of the biopsies free of tumor, 49/54 interpreted as normocellular and 16/17 hypocellular or aplastic confirmed the scan interpretation. Of the biopsies demonstrating tumor, 10/11 of those interpreted as normocellular and 14/15 hypocellular or aplastic confirmed the scan interpretation. The 111InCl3 bone marrow scan is accurate in depicting the presence or absence of normal marrow elements, but is of value in detecting tumor only when the normal elements are extensively replaced.", "contents": "The accuracy of 111InCl3 as a bone marrow scanning agent. The number of normal cellular elements present in bone marrow biopsies was compared to the extent of uptake at corresponding sites on 111InCl3 bone marrow scans in 87 patients with malignant lymphoma. Of the biopsies free of tumor, 49/54 interpreted as normocellular and 16/17 hypocellular or aplastic confirmed the scan interpretation. Of the biopsies demonstrating tumor, 10/11 of those interpreted as normocellular and 14/15 hypocellular or aplastic confirmed the scan interpretation. The 111InCl3 bone marrow scan is accurate in depicting the presence or absence of normal marrow elements, but is of value in detecting tumor only when the normal elements are extensively replaced."} {"id": "PMID:1257438", "title": "Marked enlargement of the left lobe of the liver causing a false-positive spleen image.", "content": "In 10 patients with a markedly enlarged left lobe of the liver, the posterior (prone) views (99mTc-sulfur colloid) revealed a false-positive splenic defect. In 1 case the defect was also apparent in the anterior view. In all but 1 case this pseudodefect was not present in the posterior image obtained standing up. Use of a spleen-specific or liver-specific radionuclide agent was necessary in that case. The authors caution against diagnosis from an apparently abnormal posterior image unless proved by other measures.", "contents": "Marked enlargement of the left lobe of the liver causing a false-positive spleen image. In 10 patients with a markedly enlarged left lobe of the liver, the posterior (prone) views (99mTc-sulfur colloid) revealed a false-positive splenic defect. In 1 case the defect was also apparent in the anterior view. In all but 1 case this pseudodefect was not present in the posterior image obtained standing up. Use of a spleen-specific or liver-specific radionuclide agent was necessary in that case. The authors caution against diagnosis from an apparently abnormal posterior image unless proved by other measures."} {"id": "PMID:1257439", "title": "Clinical and angiographic features of pulmonary arteriovenous fistulas in children.", "content": "Multiple pulmonary arteriovenous fistulas were demonstrated angiographically in 8 patients who exhibited cyanosis and polycythemia during childhood. Cyanosis was first observed during infancy in 5 patients. The diffuse (telangiectatic) type was present in 2 cases, while the remainder were of the multiple discrete type with one or two dominant fistulas. The clinical and angiographic features and surgical implications of multiple pulmonary arteriovenous fistulas in these children and those reported previously are discussed.", "contents": "Clinical and angiographic features of pulmonary arteriovenous fistulas in children. Multiple pulmonary arteriovenous fistulas were demonstrated angiographically in 8 patients who exhibited cyanosis and polycythemia during childhood. Cyanosis was first observed during infancy in 5 patients. The diffuse (telangiectatic) type was present in 2 cases, while the remainder were of the multiple discrete type with one or two dominant fistulas. The clinical and angiographic features and surgical implications of multiple pulmonary arteriovenous fistulas in these children and those reported previously are discussed."} {"id": "PMID:1257440", "title": "Roentgenography of congenital dislocation of the hip.", "content": "The chronically dislocated hip of a 15-month-old girl was studied postmortem. The cartilaginous components of the pelvis (both true and false acetabula) and proximal femur were demonstrated roentgenographically and correlated with gross anatomical observations. These findings should be useful in the interpretation of radiographs in congenital hip dysplasia in children.", "contents": "Roentgenography of congenital dislocation of the hip. The chronically dislocated hip of a 15-month-old girl was studied postmortem. The cartilaginous components of the pelvis (both true and false acetabula) and proximal femur were demonstrated roentgenographically and correlated with gross anatomical observations. These findings should be useful in the interpretation of radiographs in congenital hip dysplasia in children."} {"id": "PMID:1257441", "title": "Meckel's stones: a case report.", "content": "The authors describe a case of Meckel's stones demonstrated by barium study of the small bowel. Preoperative diagnosis of Meckel's stones is extremely rare; but with knowledge of their existence, more cases should be encountered.", "contents": "Meckel's stones: a case report. The authors describe a case of Meckel's stones demonstrated by barium study of the small bowel. Preoperative diagnosis of Meckel's stones is extremely rare; but with knowledge of their existence, more cases should be encountered."} {"id": "PMID:1257442", "title": "B-scan ultrasound in the evaluation of renal failure.", "content": "Twenty-three patients with blood urea nitrogen (BUN) over 70 and thought clinically to be in renal failure were examined by ultrasound. A correct diagnosis of kidney size and the presence or absence of hydronephrosis or polycystic kidney was made in all but one instance. One kidney in a patient with end-stage renal failure was not seen ultrasonically but was subsequently demonstrated on a retrograde pyelogram. In 10 patients, excretory urography (on 4 occasions with tomography) failed to demonstrate the kidneys adequately. It is suggested that ultrasound should either be the first or second imaging technique in the investigation of patients who present in renal failure of unknown cause.", "contents": "B-scan ultrasound in the evaluation of renal failure. Twenty-three patients with blood urea nitrogen (BUN) over 70 and thought clinically to be in renal failure were examined by ultrasound. A correct diagnosis of kidney size and the presence or absence of hydronephrosis or polycystic kidney was made in all but one instance. One kidney in a patient with end-stage renal failure was not seen ultrasonically but was subsequently demonstrated on a retrograde pyelogram. In 10 patients, excretory urography (on 4 occasions with tomography) failed to demonstrate the kidneys adequately. It is suggested that ultrasound should either be the first or second imaging technique in the investigation of patients who present in renal failure of unknown cause."} {"id": "PMID:1257443", "title": "Ultrasonic characteristics of cystadenoma of the pancreas.", "content": "The authors describe the ultrasound appearance of cystadenoma of the pancreas. Such lesions may be characterized as sonolucent, with good through-transmission, slightly irregular but well-defined margins, and internal echoes from septa.", "contents": "Ultrasonic characteristics of cystadenoma of the pancreas. The authors describe the ultrasound appearance of cystadenoma of the pancreas. Such lesions may be characterized as sonolucent, with good through-transmission, slightly irregular but well-defined margins, and internal echoes from septa."} {"id": "PMID:1257444", "title": "Time, dose and volume factors in interstitial Radium implants of carcinoma of the oral tongue.", "content": "In a retrospective computer dosimetry analysis of 58 patients with carcinoma of the oral tongue treated with interstitial radium implants alone or in combination with external irradiation, dose and volume appear to be the most important factors in both local control and the incidence of necrosis; in the dose rate range commonly used in clinical interstitial radiotherapy, dose rate has no significant effect. The optimal minimum tumor doses for local control vary with the size of the primary lesion: 6,000 rads for T1 lesions and 6,500 rads for T2 lesions treated with interstitial radium implants alone and 7,500 rads for lesions treated with interstitial radium implants in combination with external irradiation. For lesions treated with implants plus external irradiation, greater local control was achieved when most of the dose was delivered through the interstitial implants. For a given volume, the incidence of necrosis was directly proportional to the degree of overdosage; for a given dose, the incidence of necrosis was directly proportional to the volume receiving the dose.", "contents": "Time, dose and volume factors in interstitial Radium implants of carcinoma of the oral tongue. In a retrospective computer dosimetry analysis of 58 patients with carcinoma of the oral tongue treated with interstitial radium implants alone or in combination with external irradiation, dose and volume appear to be the most important factors in both local control and the incidence of necrosis; in the dose rate range commonly used in clinical interstitial radiotherapy, dose rate has no significant effect. The optimal minimum tumor doses for local control vary with the size of the primary lesion: 6,000 rads for T1 lesions and 6,500 rads for T2 lesions treated with interstitial radium implants alone and 7,500 rads for lesions treated with interstitial radium implants in combination with external irradiation. For lesions treated with implants plus external irradiation, greater local control was achieved when most of the dose was delivered through the interstitial implants. For a given volume, the incidence of necrosis was directly proportional to the degree of overdosage; for a given dose, the incidence of necrosis was directly proportional to the volume receiving the dose."} {"id": "PMID:1257445", "title": "Radiographic findings in herpetic esophagitis.", "content": "The authors report a case of classic esophagitis simulating candidiasis radiographically. Endoscopy provided pathological conformation of herpes infection, showing typical multinucleated cells with intranuclear inclusion bodies.", "contents": "Radiographic findings in herpetic esophagitis. The authors report a case of classic esophagitis simulating candidiasis radiographically. Endoscopy provided pathological conformation of herpes infection, showing typical multinucleated cells with intranuclear inclusion bodies."} {"id": "PMID:1257446", "title": "Adriamycin: a possible indirect radiosensitizer of hypoxic tumor cells.", "content": "Multicellular spheroids grown in vitro provide a convenient model of nodular tumors for experimental tumor therapy studies. Adriamycin was found to inactivate cells grown as spheroids less efficiently than single cells, presumably due to enhanced cellular resistance analogous to the increased radioresistance observed when these cells are grown in close contact. Spheroid growth was retarded by a minimally toxic (0.005 mug/ml) chronic level of adriamycin; irradiation and exposure to that drug concentration were not found to be synergistic. Large adriamycin concentrations (0.5 mug/ml) present during radiation exposure produced a marked \"radiosensitization,\" presumably due to the drug-inhibitng cellular oxygen consumption and thus permitting reoxygenation of the previously hypoxic spheroid cells.", "contents": "Adriamycin: a possible indirect radiosensitizer of hypoxic tumor cells. Multicellular spheroids grown in vitro provide a convenient model of nodular tumors for experimental tumor therapy studies. Adriamycin was found to inactivate cells grown as spheroids less efficiently than single cells, presumably due to enhanced cellular resistance analogous to the increased radioresistance observed when these cells are grown in close contact. Spheroid growth was retarded by a minimally toxic (0.005 mug/ml) chronic level of adriamycin; irradiation and exposure to that drug concentration were not found to be synergistic. Large adriamycin concentrations (0.5 mug/ml) present during radiation exposure produced a marked \"radiosensitization,\" presumably due to the drug-inhibitng cellular oxygen consumption and thus permitting reoxygenation of the previously hypoxic spheroid cells."} {"id": "PMID:1257447", "title": "The effect of hyperthermia on the repair of radiation damage in plateau phase cells.", "content": "Hyperthermia (41 degrees C for 1 hr.) completely inhibited both sublethal and potentially lethal radiation damage repair by plateau phase cells taken from V79 Chinese hamsters. This suggests that there may be disadvantages in combining x-ray and heat therapies for the treatment of tumors.", "contents": "The effect of hyperthermia on the repair of radiation damage in plateau phase cells. Hyperthermia (41 degrees C for 1 hr.) completely inhibited both sublethal and potentially lethal radiation damage repair by plateau phase cells taken from V79 Chinese hamsters. This suggests that there may be disadvantages in combining x-ray and heat therapies for the treatment of tumors."} {"id": "PMID:1257448", "title": "Minimal Thorotrast deposition in parapancreatic lymph nodes.", "content": "The characteristic roentgenologic features of Thorotrast deposition in the perihepatic and parapancreatic lymphatics are described. Minimal deposits of Thorotrast were seen in the liver and spleen on the abdominal radiograph in 6 patients who had no clinical symptoms. Inquiry into the patient's history invariably disclosed angiography for vascular surgery several years earlier. The typical configuration of the affected lymph node is an oval, heavy density with a long tail, resembling a tadpole or teardrop. Other irregular radiopacities in the same area, including linear ones, probably represent colloid deposition along the lymphatics. Roentgenologic differentiation of Thorotrast deposits from pancreas stones and calcified lymph nodes is discussed.", "contents": "Minimal Thorotrast deposition in parapancreatic lymph nodes. The characteristic roentgenologic features of Thorotrast deposition in the perihepatic and parapancreatic lymphatics are described. Minimal deposits of Thorotrast were seen in the liver and spleen on the abdominal radiograph in 6 patients who had no clinical symptoms. Inquiry into the patient's history invariably disclosed angiography for vascular surgery several years earlier. The typical configuration of the affected lymph node is an oval, heavy density with a long tail, resembling a tadpole or teardrop. Other irregular radiopacities in the same area, including linear ones, probably represent colloid deposition along the lymphatics. Roentgenologic differentiation of Thorotrast deposits from pancreas stones and calcified lymph nodes is discussed."} {"id": "PMID:1257453", "title": "Anatomic variation of the thoracic duct and visualization of mediastinal lymph nodes: a lymphographic study.", "content": "Of 243 thoracic ducts (TD) demonstrated during pedal lymphography, 65 (26.8%) had anatomic variations. In 58 of 65 cases with TD variants, mediastinal lymph nodes were visualized. This suggests that the radiographic appearance of mediastinal nodes is associated with TD anatomic variations. Two or more channels in the cervical portion of the thoracic duct were seen in 195 of the 243 cases. A classification of these anatomic variations is proposed.", "contents": "Anatomic variation of the thoracic duct and visualization of mediastinal lymph nodes: a lymphographic study. Of 243 thoracic ducts (TD) demonstrated during pedal lymphography, 65 (26.8%) had anatomic variations. In 58 of 65 cases with TD variants, mediastinal lymph nodes were visualized. This suggests that the radiographic appearance of mediastinal nodes is associated with TD anatomic variations. Two or more channels in the cervical portion of the thoracic duct were seen in 195 of the 243 cases. A classification of these anatomic variations is proposed."} {"id": "PMID:1257454", "title": "A large intrapericardial cyst presenting as a cardiac abnormality.", "content": "A case of mitral regurgitation apparently caused by extrinsic pressure of the large intrapericardial cyst distorting the mitral valve is reported. The initial radiographic appearance of the cyst suggested an atypically enlarged left atrium. The mitral regurgitation subsided after surgical drainage of the cyst. The angiogram showed elevation of the right pulmonary artery and depression of the left atrium.", "contents": "A large intrapericardial cyst presenting as a cardiac abnormality. A case of mitral regurgitation apparently caused by extrinsic pressure of the large intrapericardial cyst distorting the mitral valve is reported. The initial radiographic appearance of the cyst suggested an atypically enlarged left atrium. The mitral regurgitation subsided after surgical drainage of the cyst. The angiogram showed elevation of the right pulmonary artery and depression of the left atrium."} {"id": "PMID:1257455", "title": "Anomalous inferior vena cava with accessory hemiazygos continuation.", "content": "A case of accessory hemiazygos continuation of an anomalous left inferior cava with drainage via the highest intercostal vein into the left brachiocephalic vein is reported and the embryologic and radiological significance discussed. The diagnosis is suggested on plain films by the dilated highest intercostal vein, the so-called aortic nipple, and a widened left paraspinal line.", "contents": "Anomalous inferior vena cava with accessory hemiazygos continuation. A case of accessory hemiazygos continuation of an anomalous left inferior cava with drainage via the highest intercostal vein into the left brachiocephalic vein is reported and the embryologic and radiological significance discussed. The diagnosis is suggested on plain films by the dilated highest intercostal vein, the so-called aortic nipple, and a widened left paraspinal line."} {"id": "PMID:1257456", "title": "Developmental interruption of the inferior vena cava with azygos and hemiazygos substitution. Unusual radiographic features.", "content": "Two cases of left paraspinous density are presented. An inferior vena cava anomaly was not considered in the initial case, resulting in surgical exploration. The second case was diagnosed angiographically and surgery was avoided. The importance of considering this entity in the differential diagnosis of paraspinous masses is obvious, and venography should be performed to delineate the anatomy. Concurrent cardiac catheterization should be used to rule out associated lesions such as intracardiac shunts, since there is an increased association of such lesions with this anomaly.", "contents": "Developmental interruption of the inferior vena cava with azygos and hemiazygos substitution. Unusual radiographic features. Two cases of left paraspinous density are presented. An inferior vena cava anomaly was not considered in the initial case, resulting in surgical exploration. The second case was diagnosed angiographically and surgery was avoided. The importance of considering this entity in the differential diagnosis of paraspinous masses is obvious, and venography should be performed to delineate the anatomy. Concurrent cardiac catheterization should be used to rule out associated lesions such as intracardiac shunts, since there is an increased association of such lesions with this anomaly."} {"id": "PMID:1257457", "title": "The dislocated heart: an unusual complication of major chest injury.", "content": "A case of pericardial rupture with herniation of the heart through the pericardium into the left hemithorax is described. Chest radiographs showed the heart displaced to the left with slight or no displacement of the rest of the mediastinum. The patient's condition improved following operative reduction of the heart rate and repair of the pericardial tear.", "contents": "The dislocated heart: an unusual complication of major chest injury. A case of pericardial rupture with herniation of the heart through the pericardium into the left hemithorax is described. Chest radiographs showed the heart displaced to the left with slight or no displacement of the rest of the mediastinum. The patient's condition improved following operative reduction of the heart rate and repair of the pericardial tear."} {"id": "PMID:1257458", "title": "Various applications of corpus cavernosography.", "content": "The authors believe corpus cavernosography is an important aid in the evaluation of metastatic lesions, priapism, impotence, atrophy and fibrosis of the penis, and trauma to the penis. By visualizing the emptying of the contrast material from the cavernous spaces into the veins draining the penis, it is possible to assess the length of time that the contrast material remained in the organ.", "contents": "Various applications of corpus cavernosography. The authors believe corpus cavernosography is an important aid in the evaluation of metastatic lesions, priapism, impotence, atrophy and fibrosis of the penis, and trauma to the penis. By visualizing the emptying of the contrast material from the cavernous spaces into the veins draining the penis, it is possible to assess the length of time that the contrast material remained in the organ."} {"id": "PMID:1257459", "title": "Gastrocolic fistula as a complication of benign gastric ulcer.", "content": "The authors present 3 cases which illustrate the wide spectrum of clinical presentations of gastrocolic fistula. These complications include (a) pain, feculent vomiting, and diarrhea; (b) gastrointestinal hemorrhage; and (c) peritonitis. The gastric ulcer is easily detected by a barium meal study although a barium enema may be necessary to show the fistulous communication. The relationship of this condition to steroids and acetylsalicyclic acid is stressed. Two other cases are included to illustrate the development of such a fistula and show the distinguishing features of a gastrocolic fistula due to carcinoma of the colon.", "contents": "Gastrocolic fistula as a complication of benign gastric ulcer. The authors present 3 cases which illustrate the wide spectrum of clinical presentations of gastrocolic fistula. These complications include (a) pain, feculent vomiting, and diarrhea; (b) gastrointestinal hemorrhage; and (c) peritonitis. The gastric ulcer is easily detected by a barium meal study although a barium enema may be necessary to show the fistulous communication. The relationship of this condition to steroids and acetylsalicyclic acid is stressed. Two other cases are included to illustrate the development of such a fistula and show the distinguishing features of a gastrocolic fistula due to carcinoma of the colon."} {"id": "PMID:1257460", "title": "Mediastinal pseudotumors associated with exogenous obesity.", "content": "In obese individuals, a localized deposit of normal fat may simulate a mediastinal tumor on chest radiography. It is important to consider this possibility in the differential diagnosis to avoid needless surgery and facilitate continued observation when appropriate.", "contents": "Mediastinal pseudotumors associated with exogenous obesity. In obese individuals, a localized deposit of normal fat may simulate a mediastinal tumor on chest radiography. It is important to consider this possibility in the differential diagnosis to avoid needless surgery and facilitate continued observation when appropriate."} {"id": "PMID:1257462", "title": "Spontaneous fractures of the olecranon process in rheumatoid arthritis.", "content": "Spontaneous fractures through the olecranon process occurred in 3 patients with long-standing rheumatoid arthritis. In each case the elbow was severely damaged, particularly in the midportion of the trochlear notch, which was thinned either by erosion or cyst formation. The thin trichlear notch is the weak pivot point of a lever (the olecranon process) which pivots on the distal humerus. Excess stress on the lever, by the action of the triceps on the olecranon process, will produce a fracture at the weakest point: the midtrochlear notch.", "contents": "Spontaneous fractures of the olecranon process in rheumatoid arthritis. Spontaneous fractures through the olecranon process occurred in 3 patients with long-standing rheumatoid arthritis. In each case the elbow was severely damaged, particularly in the midportion of the trochlear notch, which was thinned either by erosion or cyst formation. The thin trichlear notch is the weak pivot point of a lever (the olecranon process) which pivots on the distal humerus. Excess stress on the lever, by the action of the triceps on the olecranon process, will produce a fracture at the weakest point: the midtrochlear notch."} {"id": "PMID:1257463", "title": "Palmar arteriography in acronecrosis.", "content": "Palmar arteriography in patients with acronecrosis complicating collagen vascular disease demonstrated multiple occlusions and stenoses which were most severe in the proper digital arteries. Involvement was prevalent at points of manual stress, i.e., adjacent to metacarpal-phalangeal and interphalangeal joints. An additional observation was the presence of incomplete superficial and deep palmar arches in all instances, a finding which diametrically contrasts with anatomical studies purporting to demonstrate complete palmar arches in 80% of the normal population.", "contents": "Palmar arteriography in acronecrosis. Palmar arteriography in patients with acronecrosis complicating collagen vascular disease demonstrated multiple occlusions and stenoses which were most severe in the proper digital arteries. Involvement was prevalent at points of manual stress, i.e., adjacent to metacarpal-phalangeal and interphalangeal joints. An additional observation was the presence of incomplete superficial and deep palmar arches in all instances, a finding which diametrically contrasts with anatomical studies purporting to demonstrate complete palmar arches in 80% of the normal population."} {"id": "PMID:1257464", "title": "Development of contrast media idiosyncrasy in the dog.", "content": "A laboratory dog exhibited an altered response to injections of sodium iothalamate. This idiosyncratic response may have been predicated on an earlier series of iothalamate injections. The overt manifestations of the reactions in this dog were vomiting, hypotension, and hyperreflexia. Significant changes in several electrolyte components and serum complement levels were noted when the dog reacted to the contrast material.", "contents": "Development of contrast media idiosyncrasy in the dog. A laboratory dog exhibited an altered response to injections of sodium iothalamate. This idiosyncratic response may have been predicated on an earlier series of iothalamate injections. The overt manifestations of the reactions in this dog were vomiting, hypotension, and hyperreflexia. Significant changes in several electrolyte components and serum complement levels were noted when the dog reacted to the contrast material."} {"id": "PMID:1257465", "title": "Axillary lymphadenopathy simulating an anterior mediastinal mass on the lateral chest roentgenogram.", "content": "The radiographic impression of an anterior mediastinal mass on the lateral chest roentgenogram must be confirmed by the postero-anterior film, oblique views, or tomograms to avoid inappropriate diagnostic procedures or erroneous staging of malignant disease. Physical examination will readily demonstrate enlarged axillary lymph nodes mimicking an anterior mediastinal mass.", "contents": "Axillary lymphadenopathy simulating an anterior mediastinal mass on the lateral chest roentgenogram. The radiographic impression of an anterior mediastinal mass on the lateral chest roentgenogram must be confirmed by the postero-anterior film, oblique views, or tomograms to avoid inappropriate diagnostic procedures or erroneous staging of malignant disease. Physical examination will readily demonstrate enlarged axillary lymph nodes mimicking an anterior mediastinal mass."} {"id": "PMID:1257466", "title": "Pressure dressings and postarteriographic care of the femoral puncture site.", "content": "Patient dissatisfaction with prolonged bed rest and the discomfort caused by pressure dressings led to the following evaluation. Alternate application of pressure dressings and band-aids to femoral artery puncture sites was performed in 754 arteriographic examinations. The application of pressure dressings for 16-24 hours, especially in hypertensive patients, was found to be justified by a significant reduction in delayed bleeding requiring further medical attention. A minimum application time of 8 hours is supported because all instances of delayed bleeding occurred within 8 hours of the procedure. Arterial thrombosis is not affected by the use of pressure dressings. The rationale for recommendation of bed rest is largely anecdotal and is supported by almost all experienced angiographers responding to our questionnaire.", "contents": "Pressure dressings and postarteriographic care of the femoral puncture site. Patient dissatisfaction with prolonged bed rest and the discomfort caused by pressure dressings led to the following evaluation. Alternate application of pressure dressings and band-aids to femoral artery puncture sites was performed in 754 arteriographic examinations. The application of pressure dressings for 16-24 hours, especially in hypertensive patients, was found to be justified by a significant reduction in delayed bleeding requiring further medical attention. A minimum application time of 8 hours is supported because all instances of delayed bleeding occurred within 8 hours of the procedure. Arterial thrombosis is not affected by the use of pressure dressings. The rationale for recommendation of bed rest is largely anecdotal and is supported by almost all experienced angiographers responding to our questionnaire."} {"id": "PMID:1257473", "title": "Analysis of activity in A and C fibres under mechanical and thermal stimulation of the skin receptor field.", "content": "A conduction velocity spectrum in nerve fibres of 0.15 to 90 m/sec was found by means of electrophysiological methods of analysis and computer-aided processing of experimental data. A greater portion of the non-myelinated fibres in the cutaneous nerve proved to be afferent. Patterns of afferent impulse flows entering the central nervous system are determined under various mechanical and thermal stimulations of cat's cutaneous receptive field. Differences of these flows are considered to be the reasons for various sensation modalities. The mechanism of cutaneous mechanoreceptor excitation under temperature stimuli is discussed. Special attention is paid to the contraction of cutaneous collagen under cooling. Experimental data on the change of cutaneous mechanical properties and the electrophysiological changes corroborating the thermomechanical hypothesis of receptor excitation are given.", "contents": "Analysis of activity in A and C fibres under mechanical and thermal stimulation of the skin receptor field. A conduction velocity spectrum in nerve fibres of 0.15 to 90 m/sec was found by means of electrophysiological methods of analysis and computer-aided processing of experimental data. A greater portion of the non-myelinated fibres in the cutaneous nerve proved to be afferent. Patterns of afferent impulse flows entering the central nervous system are determined under various mechanical and thermal stimulations of cat's cutaneous receptive field. Differences of these flows are considered to be the reasons for various sensation modalities. The mechanism of cutaneous mechanoreceptor excitation under temperature stimuli is discussed. Special attention is paid to the contraction of cutaneous collagen under cooling. Experimental data on the change of cutaneous mechanical properties and the electrophysiological changes corroborating the thermomechanical hypothesis of receptor excitation are given."} {"id": "PMID:1257492", "title": "Termination of pregnancy in cases of fetal death in utero by intravenous prostaglandin F2alpha.", "content": "Delivery was induced by an intravenous infusion of prostaglandin F2alpha (PGF2alpha) in gradually increasing doses in 30 consecutive cases of fetal death in utero after the 28th week of gestation. Twenty patients delivered during the first day of prostaglandin administration, 9 on the second day, and 1 patient not until the third day of infusion. It is concluded, that intravenous PGF2alpha appears to be superior to oxytocin in termination of pregnancy under these conditions.", "contents": "Termination of pregnancy in cases of fetal death in utero by intravenous prostaglandin F2alpha. Delivery was induced by an intravenous infusion of prostaglandin F2alpha (PGF2alpha) in gradually increasing doses in 30 consecutive cases of fetal death in utero after the 28th week of gestation. Twenty patients delivered during the first day of prostaglandin administration, 9 on the second day, and 1 patient not until the third day of infusion. It is concluded, that intravenous PGF2alpha appears to be superior to oxytocin in termination of pregnancy under these conditions."} {"id": "PMID:1257493", "title": "Luteolytic activity of a synthetic prostaglandin and PGF2alpha in heifers.", "content": "Two experiments involving 44 cycling heifers were conducted to evaluate the luteolytic activity of a synthetic prostaglandin, AY 24366, and PGF2alpha. Activity was assessed by the decline in progesterone level of peripheral blood and occurrence of estrus. Progesterone concentrations of jugular blood plasma were quantified by radioimmunoassay. In the first experiment, 36 heifers were treated during diestrus with AY 24366 (A-10mg intrauterine, B-30mg intramuscular and C-60mg im) or with PGF2alpha (D-5mg iu, E-15mg im and F-30mg im). Mean progesterone 0, 24 and 48 hours after treatment were A-6.33, 5.55 and 5.06; B-6.35, 2.79 and 3.92; C-5.23, 2.69 and 3.91; D-5.19, 1.50 and 1.51; E-4.69, 0.85 and 0.61; F-6.66, 0.80 and 0.48 ng/ml. Standing estrus was observed in 1, 1, 1, 4, 5 and 6 females in groups A, B, C, D, E and F respectively within 72 hours of treatment. PGF2alpha resulted in significantly (P less than 0.01) lower progesterone at 24 and 48 hours than AY 24366. However, in administration of the latter did significantly (P less than 0.05) lower progesterone at 24 hours. In the second trial six heifers were treated with either 120 or 180mg of AY 24366 im on day 12 of the cycle. Mean progesterone declined from 3.84 to 2.12 ng/ml (P less than 0.01) by 6 hours and to 1.59 ng/ml by 12 hours. Thereafter the decline was gradual and reached a level of 0.65 ng/ml at 72 hours. All six heifers showed standing estrus at 78 +/-2 hours and were inseminated. Two in each group conceived. Doses of 15mg PGF2alpha and 120mg AY 24366 were effective in causing luteal regression, however, the latter caused respiratory discomfort for 5 to 10 minutes post treatment.", "contents": "Luteolytic activity of a synthetic prostaglandin and PGF2alpha in heifers. Two experiments involving 44 cycling heifers were conducted to evaluate the luteolytic activity of a synthetic prostaglandin, AY 24366, and PGF2alpha. Activity was assessed by the decline in progesterone level of peripheral blood and occurrence of estrus. Progesterone concentrations of jugular blood plasma were quantified by radioimmunoassay. In the first experiment, 36 heifers were treated during diestrus with AY 24366 (A-10mg intrauterine, B-30mg intramuscular and C-60mg im) or with PGF2alpha (D-5mg iu, E-15mg im and F-30mg im). Mean progesterone 0, 24 and 48 hours after treatment were A-6.33, 5.55 and 5.06; B-6.35, 2.79 and 3.92; C-5.23, 2.69 and 3.91; D-5.19, 1.50 and 1.51; E-4.69, 0.85 and 0.61; F-6.66, 0.80 and 0.48 ng/ml. Standing estrus was observed in 1, 1, 1, 4, 5 and 6 females in groups A, B, C, D, E and F respectively within 72 hours of treatment. PGF2alpha resulted in significantly (P less than 0.01) lower progesterone at 24 and 48 hours than AY 24366. However, in administration of the latter did significantly (P less than 0.05) lower progesterone at 24 hours. In the second trial six heifers were treated with either 120 or 180mg of AY 24366 im on day 12 of the cycle. Mean progesterone declined from 3.84 to 2.12 ng/ml (P less than 0.01) by 6 hours and to 1.59 ng/ml by 12 hours. Thereafter the decline was gradual and reached a level of 0.65 ng/ml at 72 hours. All six heifers showed standing estrus at 78 +/-2 hours and were inseminated. Two in each group conceived. Doses of 15mg PGF2alpha and 120mg AY 24366 were effective in causing luteal regression, however, the latter caused respiratory discomfort for 5 to 10 minutes post treatment."} {"id": "PMID:1257495", "title": "Menstrual induction with the PGF2alpha-analogue ICI 81008.", "content": "\"Menstrual Induction\" (MI) has been studied in 79 volunteers, using the therapeutic principle of \"PG-Impact\". The PGF2alpha analogue: ICI 81008 was administered under strictly aseptic precautions into the uterine cavity during the 4th week of pregnancy. The treatment catheter (inserted through the cervical canal) delivered a single dose of only 100-200 mug ICI 81008 during the pilot study with this new drug. When it was established that the side effects were acceptable, this moderately effective dose was increased at first to 200-300 mug and eventually to 400 mug. At the 400 mug dose level, 29 (76%) of the 38 study patients had complete and 8 (21%) incomplete abortions, while 1 (3%) failed to bleed. Those 9 women who had incomplete abortions or failed to abort were curetted. In comparison with PGF2alpha (428 cases) and PGE2 (114 cases), ICI 81008 (38 cases at the 400 mug level) provoked lesser side effects, excepting the transient increase in blood pressure. All patients (whose intrauterine pressure was measured) responded to the ICI 81008-impact with rapidly developing high level uterine contracture. Plasma progesterone decreased significantly if treatment was successful and insignificantly in cases of treatment failure. In current studies, the efficacy of the vaginal delivery system of ICI 81008 is examined.", "contents": "Menstrual induction with the PGF2alpha-analogue ICI 81008. \"Menstrual Induction\" (MI) has been studied in 79 volunteers, using the therapeutic principle of \"PG-Impact\". The PGF2alpha analogue: ICI 81008 was administered under strictly aseptic precautions into the uterine cavity during the 4th week of pregnancy. The treatment catheter (inserted through the cervical canal) delivered a single dose of only 100-200 mug ICI 81008 during the pilot study with this new drug. When it was established that the side effects were acceptable, this moderately effective dose was increased at first to 200-300 mug and eventually to 400 mug. At the 400 mug dose level, 29 (76%) of the 38 study patients had complete and 8 (21%) incomplete abortions, while 1 (3%) failed to bleed. Those 9 women who had incomplete abortions or failed to abort were curetted. In comparison with PGF2alpha (428 cases) and PGE2 (114 cases), ICI 81008 (38 cases at the 400 mug level) provoked lesser side effects, excepting the transient increase in blood pressure. All patients (whose intrauterine pressure was measured) responded to the ICI 81008-impact with rapidly developing high level uterine contracture. Plasma progesterone decreased significantly if treatment was successful and insignificantly in cases of treatment failure. In current studies, the efficacy of the vaginal delivery system of ICI 81008 is examined."} {"id": "PMID:1257497", "title": "High performance liquid chromotography of prostaglandins: biological applications.", "content": "Two procedures are described for separation and purification of prostaglandins by high performance liquid chromatography. Both systems show excellent resolution of PGA2, PGE2 and PGF2a. Peak definition on the micro-particle silicic acid system is particularly good with the PGs appearing in 2-3 ml of organs effluent. Studies on reproducibility showed that PGE2 and PGE2a could be recovered with a retention volume of 54.2+/-0.76 ml and 64+/-0.6 ml, respectively (n=7, mean +/-50) with good recovery. The column can be run in about one hour and can be regenerated indefinitely (greater than 200 times). The degree of purification is compatible with analysis by gas chromatography-mass spectrometry. Examples showing the application of this chromatographic method to human seminal fluid, human renal tissue, platelet rich plasma and human urine samples indicate that it makes possible analysis of these samples even at low levels.", "contents": "High performance liquid chromotography of prostaglandins: biological applications. Two procedures are described for separation and purification of prostaglandins by high performance liquid chromatography. Both systems show excellent resolution of PGA2, PGE2 and PGF2a. Peak definition on the micro-particle silicic acid system is particularly good with the PGs appearing in 2-3 ml of organs effluent. Studies on reproducibility showed that PGE2 and PGE2a could be recovered with a retention volume of 54.2+/-0.76 ml and 64+/-0.6 ml, respectively (n=7, mean +/-50) with good recovery. The column can be run in about one hour and can be regenerated indefinitely (greater than 200 times). The degree of purification is compatible with analysis by gas chromatography-mass spectrometry. Examples showing the application of this chromatographic method to human seminal fluid, human renal tissue, platelet rich plasma and human urine samples indicate that it makes possible analysis of these samples even at low levels."} {"id": "PMID:1257498", "title": "Altered levels of PGF in cat spinal cord tissue following traumatic injury.", "content": "Previous studies by others indicated that PGs were present in brain, spinal cord, and c.s.f. of several mammalian species. In the present study we compared levels of PGE and PGF by R.I.A. in spinal cord tissue from traumatized cats and cats pretreated with indomethacin prior to trauma to those of baseline and sham operated controls in order to assess for the first time, to our knowledge, whether meaningful changes in levels of PGE and PGF could be detected which might shed new light on the etiology of spinal cord trauma. Levels of PGF (nanograms/gram wet wt) in the cord segment immediately adjacent to the point of trauma were 8.05 +/- 1.50, and 13.13 +/- 1.38 for baseline and sham operated cats respectively. Spinal trauma led to more than a 100% increase in PGF levels to 29.26 +/- 3.58. Although pretreatment with indomethacin 30 min prior to trauma gave the expected blockade of the PGF response to trauma, a measurable level of PGF (2.55 +/- 0.17) was found in the cord after indomethacin. Cord levels of PGF declined after 3 hr in both sham operated and traumatized animals. PGF was maximally stimulated by trauma during the first 3 hr with little effect at 72 hr. Although carefully examined, PGE levels in cat spinal cord appeared to be virtually unaffected by trauma. These findings clearly demonstrate for the first time that traumatic injury to the spinal cord is accompanied by marked increases in PG levels at the site of trauma, and that the observed elevation in PGF in response to trauma can be blocked by indomethacin in vivo. Whether PGF changes are causally related to the etiology of spinal cord trauma, or merely represent a manifestation of PG release as a result of non-specific tissue injury, remains to be seen.", "contents": "Altered levels of PGF in cat spinal cord tissue following traumatic injury. Previous studies by others indicated that PGs were present in brain, spinal cord, and c.s.f. of several mammalian species. In the present study we compared levels of PGE and PGF by R.I.A. in spinal cord tissue from traumatized cats and cats pretreated with indomethacin prior to trauma to those of baseline and sham operated controls in order to assess for the first time, to our knowledge, whether meaningful changes in levels of PGE and PGF could be detected which might shed new light on the etiology of spinal cord trauma. Levels of PGF (nanograms/gram wet wt) in the cord segment immediately adjacent to the point of trauma were 8.05 +/- 1.50, and 13.13 +/- 1.38 for baseline and sham operated cats respectively. Spinal trauma led to more than a 100% increase in PGF levels to 29.26 +/- 3.58. Although pretreatment with indomethacin 30 min prior to trauma gave the expected blockade of the PGF response to trauma, a measurable level of PGF (2.55 +/- 0.17) was found in the cord after indomethacin. Cord levels of PGF declined after 3 hr in both sham operated and traumatized animals. PGF was maximally stimulated by trauma during the first 3 hr with little effect at 72 hr. Although carefully examined, PGE levels in cat spinal cord appeared to be virtually unaffected by trauma. These findings clearly demonstrate for the first time that traumatic injury to the spinal cord is accompanied by marked increases in PG levels at the site of trauma, and that the observed elevation in PGF in response to trauma can be blocked by indomethacin in vivo. Whether PGF changes are causally related to the etiology of spinal cord trauma, or merely represent a manifestation of PG release as a result of non-specific tissue injury, remains to be seen."} {"id": "PMID:1257499", "title": "Prostaglandin synthesis does not mediate the pulmonary vasodilatory effect of acetylcholine.", "content": "We wondered if inhibition of hypoxic pulmonary vasoconstriction by acetylcholine was mediated by prostaglandin synthesis. In 5 calves at a simulated altitude of 4,570 m, acetylcholine (10 mug/kg/min) decreased mean pulmonary arterial pressure and total pulmonary resistance by 24 +/- 2 and 35 +/- 3% before and by 21 +/- 2 and 27 +/- 4% after the administration of meclofenamate (2 mg/kg). Since there was no difference in the effect of acetylcholine before and after meclofenamate, it was concluded that pulmonary vasodilation by activation of muscarinic receptors was not dependent on prostaglandin synthesis.", "contents": "Prostaglandin synthesis does not mediate the pulmonary vasodilatory effect of acetylcholine. We wondered if inhibition of hypoxic pulmonary vasoconstriction by acetylcholine was mediated by prostaglandin synthesis. In 5 calves at a simulated altitude of 4,570 m, acetylcholine (10 mug/kg/min) decreased mean pulmonary arterial pressure and total pulmonary resistance by 24 +/- 2 and 35 +/- 3% before and by 21 +/- 2 and 27 +/- 4% after the administration of meclofenamate (2 mg/kg). Since there was no difference in the effect of acetylcholine before and after meclofenamate, it was concluded that pulmonary vasodilation by activation of muscarinic receptors was not dependent on prostaglandin synthesis."} {"id": "PMID:1257500", "title": "Aspirin and exercise-induced asthma.", "content": "In four subjects with exercise-induced asthma, aspirin and placebo were administered prior to exercise in a double blind study. Pulmonary function tests did not reveal any difference between the response after aspirin or placebo. We conclude that in these four subjects aspirin did not prevent the bronchoconstrictor response. This might suggest that prostaglandins have no significant role in exercise-induced asthma.", "contents": "Aspirin and exercise-induced asthma. In four subjects with exercise-induced asthma, aspirin and placebo were administered prior to exercise in a double blind study. Pulmonary function tests did not reveal any difference between the response after aspirin or placebo. We conclude that in these four subjects aspirin did not prevent the bronchoconstrictor response. This might suggest that prostaglandins have no significant role in exercise-induced asthma."} {"id": "PMID:1257501", "title": "Relative biological activity of certain prostaglandins and their enantiomers.", "content": "A series of mirror image (ent) forms of prostaglandins F2 and E2 have been compared for potency in a hamster antifertility test. In the PGF2 series, ent-compounds surveyed had less potency than corresponding natural structures. For the PGE2 series, 11alpha-(15S)-ent-PGE2 methyl ester was 10-fold more potent than PGE2. Altering the C-9 hydroxy configuration in the PGF2 series from the natural alpha to beta decreased potency dramatically for compounds tested.", "contents": "Relative biological activity of certain prostaglandins and their enantiomers. A series of mirror image (ent) forms of prostaglandins F2 and E2 have been compared for potency in a hamster antifertility test. In the PGF2 series, ent-compounds surveyed had less potency than corresponding natural structures. For the PGE2 series, 11alpha-(15S)-ent-PGE2 methyl ester was 10-fold more potent than PGE2. Altering the C-9 hydroxy configuration in the PGF2 series from the natural alpha to beta decreased potency dramatically for compounds tested."} {"id": "PMID:1257566", "title": "[Thiol groups of chicken liver LDH (author's transl)].", "content": "Crystallized chicken liver H4 lactatedehydrogenase with PCBM and DTNB, proved to have sic thiol groups per enzyme molecule. Sulphydryl groups seemed necessary for activity since the enzyme became inactive when the groups were blocked by PCMB, DTNB or by Zn (II), Cu (II) or Hg (II). LDH inhibited by Hg (II) recovered its activity after treatment with beta-mercaptoentanol. LDH reversible inactivation, caused by PCMB, was partially impeded by NAD, NADH hand L-lactate but inactivation caused by DTNB was impeded in any way by coenzymes or substrates. PCMB is a competitive inhibitor with the coenzymes but is non-competitive with the substrates whereas DTNB is a competitive inhibitor with NADH or L-lactate. Kinetic studies of the DTNB inactivation suggest the possible formation of a DTNB-LDH-NADH complex. The formation of LDH-NADH and LDH-NAD pyruvate inactive complexes have been detected by U.V. absorbancy measurements. Such inactive complexes have equally been observed experimenting with the PCMB of Hg (II) previously treated enzyme. The results showed that these essential sulphydryl groups are not involved in th attaching of coenzymes or substrates to the chicken liver LDH molecule, but they seem to suggest the participation of --SH groups during the reversible hydrogen transfer between NADH and pyruvate.", "contents": "[Thiol groups of chicken liver LDH (author's transl)]. Crystallized chicken liver H4 lactatedehydrogenase with PCBM and DTNB, proved to have sic thiol groups per enzyme molecule. Sulphydryl groups seemed necessary for activity since the enzyme became inactive when the groups were blocked by PCMB, DTNB or by Zn (II), Cu (II) or Hg (II). LDH inhibited by Hg (II) recovered its activity after treatment with beta-mercaptoentanol. LDH reversible inactivation, caused by PCMB, was partially impeded by NAD, NADH hand L-lactate but inactivation caused by DTNB was impeded in any way by coenzymes or substrates. PCMB is a competitive inhibitor with the coenzymes but is non-competitive with the substrates whereas DTNB is a competitive inhibitor with NADH or L-lactate. Kinetic studies of the DTNB inactivation suggest the possible formation of a DTNB-LDH-NADH complex. The formation of LDH-NADH and LDH-NAD pyruvate inactive complexes have been detected by U.V. absorbancy measurements. Such inactive complexes have equally been observed experimenting with the PCMB of Hg (II) previously treated enzyme. The results showed that these essential sulphydryl groups are not involved in th attaching of coenzymes or substrates to the chicken liver LDH molecule, but they seem to suggest the participation of --SH groups during the reversible hydrogen transfer between NADH and pyruvate."} {"id": "PMID:1257567", "title": "[Pharmacological reactivity in cricetus aureus uterus (author's transl)].", "content": "The motility of the isolated Cricetus auratus uterus was studied and compared to that of other species. Oxitocyn, epinephrine, norepinephrine, histamine, 5-hydroxy-tryptamine and acetylcholine were used as spasmogen agents. There was not contractil response with epinephrine or nor-epinephrine. Histamine reduced basal tonus. There was contraction with acetylcholine, oxytocin and 5-hydroxy-tryptamine. Cricetus auratus uterus appeared more sensitive when the contraction was registered by the isometric method. No taquifilaxy was produced by 5-hydroxy-tryptamine, as opposed to such effect in rat uterus. The Cricetus auratus uterus has, therefore, shown similar reactivity to that of rat, but different from rabbit and guinea-pig.", "contents": "[Pharmacological reactivity in cricetus aureus uterus (author's transl)]. The motility of the isolated Cricetus auratus uterus was studied and compared to that of other species. Oxitocyn, epinephrine, norepinephrine, histamine, 5-hydroxy-tryptamine and acetylcholine were used as spasmogen agents. There was not contractil response with epinephrine or nor-epinephrine. Histamine reduced basal tonus. There was contraction with acetylcholine, oxytocin and 5-hydroxy-tryptamine. Cricetus auratus uterus appeared more sensitive when the contraction was registered by the isometric method. No taquifilaxy was produced by 5-hydroxy-tryptamine, as opposed to such effect in rat uterus. The Cricetus auratus uterus has, therefore, shown similar reactivity to that of rat, but different from rabbit and guinea-pig."} {"id": "PMID:1257568", "title": "[Kinetics of renin reaction in rat plasma (author's transl)].", "content": "Important kinetic aspects of renin reaction were studied in order to evaluate the parameters that regulate the formation rate of angiotensin I. This rate decreased throughout the incubation period of normal rat plasma and it showed a linear increase when plasma was incubated with renin-substrate. When renin was added to normal rat plasma a plateau in the angiotensin I formation rate occurred after 4-6 hours. When plasma samples containing increasing amounts of renin-substrate were incubated, the velocity of their reaction increased in proportion to the renin-substrate concentration. Under these incubation conditions, the reaction between endogenous renin and renin-substrate in normal rat plasma, proved to be a first kinetic order with respect to the substrate.", "contents": "[Kinetics of renin reaction in rat plasma (author's transl)]. Important kinetic aspects of renin reaction were studied in order to evaluate the parameters that regulate the formation rate of angiotensin I. This rate decreased throughout the incubation period of normal rat plasma and it showed a linear increase when plasma was incubated with renin-substrate. When renin was added to normal rat plasma a plateau in the angiotensin I formation rate occurred after 4-6 hours. When plasma samples containing increasing amounts of renin-substrate were incubated, the velocity of their reaction increased in proportion to the renin-substrate concentration. Under these incubation conditions, the reaction between endogenous renin and renin-substrate in normal rat plasma, proved to be a first kinetic order with respect to the substrate."} {"id": "PMID:1257569", "title": "Electron microscopic evidence for phagocytic properties of human peripheral mononuclear cells cultured with PHA.", "content": "The time course of the ultrastructural changes induced in human peripheral mononuclear cells, when cultured with PHA, has been studied. In addition to findings common to many mitotic cells, such as an increase in nuclear and nucleolar size, the presence of free polyribosomes, glycogen and lipid globules in the cytoplasma, and a high number of mitochondria, agglutinating properties due to PHA per se were observed in the first 12 hours. At 72 hours certain cells developed phagocytic-like properties, i.e. they were able to incorporate both material from the extracellular compartment and syngeneic cells. These results are discussed suggesting the possible presence of macrophages in culture or the ability of activated T cells to express it.", "contents": "Electron microscopic evidence for phagocytic properties of human peripheral mononuclear cells cultured with PHA. The time course of the ultrastructural changes induced in human peripheral mononuclear cells, when cultured with PHA, has been studied. In addition to findings common to many mitotic cells, such as an increase in nuclear and nucleolar size, the presence of free polyribosomes, glycogen and lipid globules in the cytoplasma, and a high number of mitochondria, agglutinating properties due to PHA per se were observed in the first 12 hours. At 72 hours certain cells developed phagocytic-like properties, i.e. they were able to incorporate both material from the extracellular compartment and syngeneic cells. These results are discussed suggesting the possible presence of macrophages in culture or the ability of activated T cells to express it."} {"id": "PMID:1257570", "title": "[Parasympathetic control of secretion of pancreatic juice in the rabbit (author's transl)].", "content": "The secretion of pancreatic juice in response to stimulation of the vagus nerves in the neck, and to injection of parasympathomimetic drugs, was studied in anesthetized rabbits. Vagal stimulation caused a marked increase of protein content in pancreatic juice, and also a small increase in flow of juice, highly variable from one amimal to another, preceded by a short period of inhibition. Atropine supressed vagal effect on protein concentration, but failed to abolish the flow response. Injection of parasympathomimetic drugs closely imitated the results of vagal stimulation, with the difference that secretory action was fully abolished by atropine. The possibility that effects the parasympathetic stimulation on the flow of juice were secondary to vasodilatation, was discussed. The obtained data were compared with those described for other mammalian species, and the conclusion was reached that rabbit behaves like carnivora rather than herbivora.", "contents": "[Parasympathetic control of secretion of pancreatic juice in the rabbit (author's transl)]. The secretion of pancreatic juice in response to stimulation of the vagus nerves in the neck, and to injection of parasympathomimetic drugs, was studied in anesthetized rabbits. Vagal stimulation caused a marked increase of protein content in pancreatic juice, and also a small increase in flow of juice, highly variable from one amimal to another, preceded by a short period of inhibition. Atropine supressed vagal effect on protein concentration, but failed to abolish the flow response. Injection of parasympathomimetic drugs closely imitated the results of vagal stimulation, with the difference that secretory action was fully abolished by atropine. The possibility that effects the parasympathetic stimulation on the flow of juice were secondary to vasodilatation, was discussed. The obtained data were compared with those described for other mammalian species, and the conclusion was reached that rabbit behaves like carnivora rather than herbivora."} {"id": "PMID:1257571", "title": "Validation of a heterologous radioimmunoassay for the determination of rat thyrotrophic hormone.", "content": "A heterologous RIA system is described for the determination of TSH in rat plasma. The antibody was obtained by us in guinea-pigs and directed against bovine-TSH (B-TSH). It was chosen from several antisera as the one showing the greatest potency in vivo against rat TSH, using the McKenzie bioassay. Two different antigens were tried for radioiodination: B-TSH (B-TSH) and a purified mouse tumour TSH (M-TSH). The choice of labeled antigen proved to be critical. It was not possible to develop a reliable RIA with B-TSH. Using M-TSH, however, a RIA was developed which is sensitive enough to detect differences between normal and lower than normal plasma TSH levels. The reproducibility, sensitivity and specificity of the RIA are described, as well as several procedures which shorten the time spent on a given assay, and at the same time decrease inter and intra-assay variations. Some of the results obtained with experimental plasmas were compared to the in vivo potency of the samples in the McKenzie bioassay. The results obtained with the present RIA have also been validated physiologically by carrying out the determinations on plasmas obtained from rats submitted to situations known to decrease (hypophysectomy, treatment with thyroid hormones, ether anaesthesia) or increase (injection of TRH, thyroidectomy, treatment with goitrogens) circulating TSH levels. The circulating TSH levels of normal rats found with the present RIA compare well with values obtained with the homologous immunoreactants available from NIAMDD at NIH (U.S.A.).", "contents": "Validation of a heterologous radioimmunoassay for the determination of rat thyrotrophic hormone. A heterologous RIA system is described for the determination of TSH in rat plasma. The antibody was obtained by us in guinea-pigs and directed against bovine-TSH (B-TSH). It was chosen from several antisera as the one showing the greatest potency in vivo against rat TSH, using the McKenzie bioassay. Two different antigens were tried for radioiodination: B-TSH (B-TSH) and a purified mouse tumour TSH (M-TSH). The choice of labeled antigen proved to be critical. It was not possible to develop a reliable RIA with B-TSH. Using M-TSH, however, a RIA was developed which is sensitive enough to detect differences between normal and lower than normal plasma TSH levels. The reproducibility, sensitivity and specificity of the RIA are described, as well as several procedures which shorten the time spent on a given assay, and at the same time decrease inter and intra-assay variations. Some of the results obtained with experimental plasmas were compared to the in vivo potency of the samples in the McKenzie bioassay. The results obtained with the present RIA have also been validated physiologically by carrying out the determinations on plasmas obtained from rats submitted to situations known to decrease (hypophysectomy, treatment with thyroid hormones, ether anaesthesia) or increase (injection of TRH, thyroidectomy, treatment with goitrogens) circulating TSH levels. The circulating TSH levels of normal rats found with the present RIA compare well with values obtained with the homologous immunoreactants available from NIAMDD at NIH (U.S.A.)."} {"id": "PMID:1257572", "title": "Ferritin intestinal absorption.", "content": "Ferritin as a source of iron was consiered. A good iron absorption rate appears in normal rats with an in vivo absorption technique. The same absorption appears in iron-deficient animals. The iron stored in intestinal wall is lower in anemic rats than in normal ones, suggesting a higher draw of iron from lumen to blood.", "contents": "Ferritin intestinal absorption. Ferritin as a source of iron was consiered. A good iron absorption rate appears in normal rats with an in vivo absorption technique. The same absorption appears in iron-deficient animals. The iron stored in intestinal wall is lower in anemic rats than in normal ones, suggesting a higher draw of iron from lumen to blood."} {"id": "PMID:1257574", "title": "[LDH and structural analogues of pyruvate (author's transl)].", "content": "Pyruvate related compounds have been tested for their active or inhibitory properties on LDH. Special structure features were needed for compounds to be bound to the enzyme active site. Pyruvate and the LDH molecule were bound by the interaction of the carboxyl group or its ester derivative, with the enzyme. Ethyl pyruvate seemed to behave as a substrate of the enzyme whereas acetophenone, ethyl acetoacetate and beta-oxoglutarate did not act as substrates or inhibitors of LDH. Phenyl pyruvate, alpha-oxoglutarate and L-mandelate are not substrates but inhibitors of the LDH. It seems that a structure having a carbonyl group in the alpha-position to the carboxyl is required for the binding of a compound to the LDH molecule. Glyoxylate alpha-oxobutyrate and alpha-oxovalerianate appear to be worse LDH substrates than pyruvate itself. This seems to suggest that the shortening or the extension of the pyruvate aliphatic chain induces a decrease of the affinity of the enzyme towards their substrate homologues.", "contents": "[LDH and structural analogues of pyruvate (author's transl)]. Pyruvate related compounds have been tested for their active or inhibitory properties on LDH. Special structure features were needed for compounds to be bound to the enzyme active site. Pyruvate and the LDH molecule were bound by the interaction of the carboxyl group or its ester derivative, with the enzyme. Ethyl pyruvate seemed to behave as a substrate of the enzyme whereas acetophenone, ethyl acetoacetate and beta-oxoglutarate did not act as substrates or inhibitors of LDH. Phenyl pyruvate, alpha-oxoglutarate and L-mandelate are not substrates but inhibitors of the LDH. It seems that a structure having a carbonyl group in the alpha-position to the carboxyl is required for the binding of a compound to the LDH molecule. Glyoxylate alpha-oxobutyrate and alpha-oxovalerianate appear to be worse LDH substrates than pyruvate itself. This seems to suggest that the shortening or the extension of the pyruvate aliphatic chain induces a decrease of the affinity of the enzyme towards their substrate homologues."} {"id": "PMID:1257575", "title": "The incorporation of hydrophobic protein receptors and artificial lipid membranes.", "content": "The mechanism of chemical synaptic transmission implies: 1) the existence of a specific protein receptor at the postsynaptic membrane, and 2) the interaction between the transmitter released and the receptor, thus producing a change in ionic permeability. Previous studies from our laboratory have shown that special hydrophobic proteins extracted from postsynpatic membranes of different tissues showed a high affinity binding for the different pharmacological agents. The present paper describes experiments in which different hydrophobic protein binding acetylcholine, noradrenaline, gamma-aminobutyric acid, and glutamate were incorporated into artificial lipid membranes, similar to those first described by Mueller et al. (19). The effect of the different pharmacological agents was tested under experimental conditions of voltage clamp and the d.c. current changes measured. The results were then compared for the different lipid-protein membranes employed during the steady state and during transient conductance changes. The specificity of the responses indicate that artificial lipid membranes containing these hydrophobic proteins from electroplax, myocardium, spleen capsule and shrimp muscle can be used as a model to study pharmacologic receptors.", "contents": "The incorporation of hydrophobic protein receptors and artificial lipid membranes. The mechanism of chemical synaptic transmission implies: 1) the existence of a specific protein receptor at the postsynaptic membrane, and 2) the interaction between the transmitter released and the receptor, thus producing a change in ionic permeability. Previous studies from our laboratory have shown that special hydrophobic proteins extracted from postsynpatic membranes of different tissues showed a high affinity binding for the different pharmacological agents. The present paper describes experiments in which different hydrophobic protein binding acetylcholine, noradrenaline, gamma-aminobutyric acid, and glutamate were incorporated into artificial lipid membranes, similar to those first described by Mueller et al. (19). The effect of the different pharmacological agents was tested under experimental conditions of voltage clamp and the d.c. current changes measured. The results were then compared for the different lipid-protein membranes employed during the steady state and during transient conductance changes. The specificity of the responses indicate that artificial lipid membranes containing these hydrophobic proteins from electroplax, myocardium, spleen capsule and shrimp muscle can be used as a model to study pharmacologic receptors."} {"id": "PMID:1257576", "title": "Control of ion movement by cardiac sarcolemma.", "content": "The cation affinity sequence based on 45Ca displacement from neonatal rat heart tissue culture cells was La greater than Cd greater than Zn greater than Mn greater than Mg. This sequence correlated with the rate at which these ions diminished contractile tension in neonatal rat papillary muscles. In adult rat interventricular septa elevated extracellular Mg diminished tension development concomitant with a decrease in 45Ca influx. The results support the hypothesis that these cations interfere with contraction by occupying sarcolemmal sites ordinarily reserved for calcium or by interfering with transmembrane Ca movements, both of which are crucial for tension development. The data of Bockman et al. (2) provides further support for this hypothesis. Elevated extracellular Mg reduced potassium exchange by 30% in adult rat interventricular septa but had no effect on 42K EXCHANGE IN CONTROL RABBIT INterventricular septa. Elevated extracellular Mg did inhibit the net 42K loss induced by digitalis glycoside without affecting tension development or glycoside inhibition of 42K influx in the rabbit heart. High Mg also attenuated the increase in 42K exchange produced by elevated extracellular potassium. These data demonstrate that glycoside inotropy is not dependent on potassium loss from myocardium but are consistent with the hypothesis that increased intracellular sodium mediates glycoside inotropy. A model for the effects of Mg in rat and rabbit heart is presented.", "contents": "Control of ion movement by cardiac sarcolemma. The cation affinity sequence based on 45Ca displacement from neonatal rat heart tissue culture cells was La greater than Cd greater than Zn greater than Mn greater than Mg. This sequence correlated with the rate at which these ions diminished contractile tension in neonatal rat papillary muscles. In adult rat interventricular septa elevated extracellular Mg diminished tension development concomitant with a decrease in 45Ca influx. The results support the hypothesis that these cations interfere with contraction by occupying sarcolemmal sites ordinarily reserved for calcium or by interfering with transmembrane Ca movements, both of which are crucial for tension development. The data of Bockman et al. (2) provides further support for this hypothesis. Elevated extracellular Mg reduced potassium exchange by 30% in adult rat interventricular septa but had no effect on 42K EXCHANGE IN CONTROL RABBIT INterventricular septa. Elevated extracellular Mg did inhibit the net 42K loss induced by digitalis glycoside without affecting tension development or glycoside inhibition of 42K influx in the rabbit heart. High Mg also attenuated the increase in 42K exchange produced by elevated extracellular potassium. These data demonstrate that glycoside inotropy is not dependent on potassium loss from myocardium but are consistent with the hypothesis that increased intracellular sodium mediates glycoside inotropy. A model for the effects of Mg in rat and rabbit heart is presented."} {"id": "PMID:1257577", "title": "Correlation between changes in endogenous catecholamine release from the heart and various physiological responses in anesthetized dogs.", "content": "Correlations between the concentration of endogenous catecholamines in coronary sinus blood and various physiological responses to adrenergic stimulation were studied in anesthetized dogs. Plasma catecholamine levels both in coronary sinus and aortic blood were measured by means of a modification of the radiometric-enzymatic assay for tissue catecholamines, and found to be 0.769 +/- 0.110(S.E.) and 0.972 +/-0.127(S.E.) ng/ml, respectively, under basal conditions. Circulating catecholamine levels increased after the intracoronary injection of 6-hydroxydopamine, which has an indirect sympathomimetic action. Both the increment in catecholamine release from the heart and the intensity of physiological response were dose-related. A frequency-dependent increase in coronary sinus blood catecholamine levels occurred during right cardioaccelerator nerve stimulation. Maximum values were observed with a stimulation frequency of 10 Hz, at which maximum physiological responses were obtained. A highly significant correlation was found between endogenous catecholamine levels in coronary sinus blood and the dp/dt of left ventricular pressure (r = 0.750, p less than 0.001), as well as mean coronary blood flow (r =0.706, p less than 0.001). The present preparation may prove to be a reliable means of studying the role of the sympathetic system in regulating cardiac function.", "contents": "Correlation between changes in endogenous catecholamine release from the heart and various physiological responses in anesthetized dogs. Correlations between the concentration of endogenous catecholamines in coronary sinus blood and various physiological responses to adrenergic stimulation were studied in anesthetized dogs. Plasma catecholamine levels both in coronary sinus and aortic blood were measured by means of a modification of the radiometric-enzymatic assay for tissue catecholamines, and found to be 0.769 +/- 0.110(S.E.) and 0.972 +/-0.127(S.E.) ng/ml, respectively, under basal conditions. Circulating catecholamine levels increased after the intracoronary injection of 6-hydroxydopamine, which has an indirect sympathomimetic action. Both the increment in catecholamine release from the heart and the intensity of physiological response were dose-related. A frequency-dependent increase in coronary sinus blood catecholamine levels occurred during right cardioaccelerator nerve stimulation. Maximum values were observed with a stimulation frequency of 10 Hz, at which maximum physiological responses were obtained. A highly significant correlation was found between endogenous catecholamine levels in coronary sinus blood and the dp/dt of left ventricular pressure (r = 0.750, p less than 0.001), as well as mean coronary blood flow (r =0.706, p less than 0.001). The present preparation may prove to be a reliable means of studying the role of the sympathetic system in regulating cardiac function."} {"id": "PMID:1257578", "title": "Metabolic alterations following chemical sympathectomy with 6-hydroxydopamine in the rat.", "content": "Until recently the role of the sympathetic nervous system on intermediary metabolism has been difficult to study because of the lack of efficient methods of producing generalized sympathectomy. Various metabolic parameters were measured 24 hr, 72 hr, and 1 week after chemical sympathectomy produced by a single intravenous injection of 6-hydroxydopamine (100 mg/kg) in rats. All animals were fasted 16 hr previous to all measurements. A marked increase was found in blood glucose levels in 6-OH-DA-treated animals. Serum free fatty acids (FFA) were 2 1/2 times higher 24 hr after sympathectomy than in control animals, but returned to normal values thereafter. The glycogen content of the liver was 10 times greater in treated animals 24 hr after 6-OH-DA, whereas cardiac glycogen was more than doubled 72 hr after sympathectomy. In contrast, glycogen content of skeletal muscle was only slightly but insignificantly increased. Immunoreactive insulin levels were also increased by 70 percent in sympathectomized animals after 24 hr, but returned to normal values thereafter. These results indicate an important alteration of carbohydrate and lipid metabolism after chemical sympathectomy, thus supporting a role of the sympathetic nervous system in their regulation.", "contents": "Metabolic alterations following chemical sympathectomy with 6-hydroxydopamine in the rat. Until recently the role of the sympathetic nervous system on intermediary metabolism has been difficult to study because of the lack of efficient methods of producing generalized sympathectomy. Various metabolic parameters were measured 24 hr, 72 hr, and 1 week after chemical sympathectomy produced by a single intravenous injection of 6-hydroxydopamine (100 mg/kg) in rats. All animals were fasted 16 hr previous to all measurements. A marked increase was found in blood glucose levels in 6-OH-DA-treated animals. Serum free fatty acids (FFA) were 2 1/2 times higher 24 hr after sympathectomy than in control animals, but returned to normal values thereafter. The glycogen content of the liver was 10 times greater in treated animals 24 hr after 6-OH-DA, whereas cardiac glycogen was more than doubled 72 hr after sympathectomy. In contrast, glycogen content of skeletal muscle was only slightly but insignificantly increased. Immunoreactive insulin levels were also increased by 70 percent in sympathectomized animals after 24 hr, but returned to normal values thereafter. These results indicate an important alteration of carbohydrate and lipid metabolism after chemical sympathectomy, thus supporting a role of the sympathetic nervous system in their regulation."} {"id": "PMID:1257579", "title": "Valinomycin inhibition of the inward slow current of cardiac muscle.", "content": "Valinomycin (10(-6) M), a K+ ionophore and uncoupler of oxidative phosphorylation, produced pronounced shortening of the action potential plateau in young (3 day) and old (15-19 day) embryonic chick hearts and isolated perfused guinea pig hearts. The rate of rise of the action potential was usually not affected. Dimethylsulfoxide (DMSO) (2 percent), The vehicle for valinomycin, did not cause plateau shortening. In chick hearts, diminution of the plateau by valinomycin at 10(-6) M usually occurred by 1 hr; larger doses produced prominent effects within 15 min. Young embryonic hearts were more resistant to valinomycin, and 20x10(-6) M for 1-2 hr was necessary to produce a significant diminution in plateau. Several agents were able to partially relengthen the plateau shortened by valinomycin. In both young and old hearts, the resting potential was not increased by valinomycin, even though young hearts have a low resting potential because of a low K+ conductance (gK). In guinea pig, 10(-6) M valinomycin markedly shortened the plateau within 5-10 min. Contractions were abolished, i.e., the hearts became electromechanically uncoupled. When hearts were perfused with 27 mM K+ to depolarize the cells to about -40 mV to inactivate fast Na+ channels, catecholamines or methylxanthines rapidly induced slowly rising (about 10 V/sec), overshooting, plateau-like responses with accompanying contractions. Valinomycin rapidly (within 2-5 min) abolished these slow responses and contractions. Hearts perfused with 10(-6) M valinomycin or 10(-5) dinitrophenol became nearly entirely depleted of ATP within 2-10 min. These results suggest that valinomycin blocks the slow inward current indirectly through ATP depletion, the slow cation channels requiring metabolic energy. The possibility that resting gK or kinetics of changes in gK during the plateau is also affected by valinomycin cannot be excluded.", "contents": "Valinomycin inhibition of the inward slow current of cardiac muscle. Valinomycin (10(-6) M), a K+ ionophore and uncoupler of oxidative phosphorylation, produced pronounced shortening of the action potential plateau in young (3 day) and old (15-19 day) embryonic chick hearts and isolated perfused guinea pig hearts. The rate of rise of the action potential was usually not affected. Dimethylsulfoxide (DMSO) (2 percent), The vehicle for valinomycin, did not cause plateau shortening. In chick hearts, diminution of the plateau by valinomycin at 10(-6) M usually occurred by 1 hr; larger doses produced prominent effects within 15 min. Young embryonic hearts were more resistant to valinomycin, and 20x10(-6) M for 1-2 hr was necessary to produce a significant diminution in plateau. Several agents were able to partially relengthen the plateau shortened by valinomycin. In both young and old hearts, the resting potential was not increased by valinomycin, even though young hearts have a low resting potential because of a low K+ conductance (gK). In guinea pig, 10(-6) M valinomycin markedly shortened the plateau within 5-10 min. Contractions were abolished, i.e., the hearts became electromechanically uncoupled. When hearts were perfused with 27 mM K+ to depolarize the cells to about -40 mV to inactivate fast Na+ channels, catecholamines or methylxanthines rapidly induced slowly rising (about 10 V/sec), overshooting, plateau-like responses with accompanying contractions. Valinomycin rapidly (within 2-5 min) abolished these slow responses and contractions. Hearts perfused with 10(-6) M valinomycin or 10(-5) dinitrophenol became nearly entirely depleted of ATP within 2-10 min. These results suggest that valinomycin blocks the slow inward current indirectly through ATP depletion, the slow cation channels requiring metabolic energy. The possibility that resting gK or kinetics of changes in gK during the plateau is also affected by valinomycin cannot be excluded."} {"id": "PMID:1257580", "title": "The effect of digoxin antibody on the washout of tritiated digoxin and its inotropic effect from perfused rabbit hearts.", "content": "The reversal of digoxin effects by digoxin antibody (Ab) may be mediated by at least two mechanisms. First, the Ab may simply decrease the concentration of free digoxin in the perfusing medium, or second, the Ab may dislodge digoxin from its receptor. To pursue this problem, rabbit hearts were perfused for 20 min with Krebs-Henseleit solution (K-H) followed by a 30-min perfusion with [3H] digoxin in concentrations of 10(-7), 5x10(-7), and 10(-6) M. The hearts were then washed out with K-H alone or with K-H containing Ab. During washout the effluent was collected at 30-sec intervals and the concentration of [3H] digoxin measured in each sample. Washout was continued until the positive inotropic effect of digoxin had returned to its previous level. The [3H] digoxin washout curves were analyzed on the basis of statistical criteria and yielded three exponential components. During Ab washout the half-times t1/2 of these components were 0-25 +/- 0.07, 1.70 +/- 0.28, and 19.5 +/- 6.9 min, while during K-H washout the values were 0.28 +/- 0.02, 1.49 +/- 0.22, and 11.8 +/- 2.7. The decay of the inotropic effect of digoxin was similar during both washout conditions. The results indicate that the apparent tissue to perfusate concentration gradient for the washout of [3H] digoxin was not increased by Ab...", "contents": "The effect of digoxin antibody on the washout of tritiated digoxin and its inotropic effect from perfused rabbit hearts. The reversal of digoxin effects by digoxin antibody (Ab) may be mediated by at least two mechanisms. First, the Ab may simply decrease the concentration of free digoxin in the perfusing medium, or second, the Ab may dislodge digoxin from its receptor. To pursue this problem, rabbit hearts were perfused for 20 min with Krebs-Henseleit solution (K-H) followed by a 30-min perfusion with [3H] digoxin in concentrations of 10(-7), 5x10(-7), and 10(-6) M. The hearts were then washed out with K-H alone or with K-H containing Ab. During washout the effluent was collected at 30-sec intervals and the concentration of [3H] digoxin measured in each sample. Washout was continued until the positive inotropic effect of digoxin had returned to its previous level. The [3H] digoxin washout curves were analyzed on the basis of statistical criteria and yielded three exponential components. During Ab washout the half-times t1/2 of these components were 0-25 +/- 0.07, 1.70 +/- 0.28, and 19.5 +/- 6.9 min, while during K-H washout the values were 0.28 +/- 0.02, 1.49 +/- 0.22, and 11.8 +/- 2.7. The decay of the inotropic effect of digoxin was similar during both washout conditions. The results indicate that the apparent tissue to perfusate concentration gradient for the washout of [3H] digoxin was not increased by Ab..."} {"id": "PMID:1257581", "title": "On the mechanisms underlying digitalis toxicity in cardiac Purkinje fibers.", "content": "The different mechanisms by which digitalis enhances pacemaker automaticity in canine Purkinje fibers has been studied under different conditions. Transmembrane potentials of quiescent, spontaneously active, or electrically driven fibers were recorded in the presence and absence of strophanthidin (10(-5)-10(-7) M). In quiescent fibers, strophanthidin caused the membrane potential to depolarize and to develop oscillations of progressively larger magnitude which were followed by spontaneous activity. In spontaneously active preparations strophanthidin enhanced the slope of diastolic depolarization and therefore the rate of discharge. In both cases, there was no evidence of oscillations during diastolic depolarization. A steepening of diastolic depolarizations without superimposed oscillations (and eventually also followed by spontaneous activity) was observed in preparations driven electrically at very slow rates. However, in fibers driven at faster rates (30/min or more) in the presence of ouabain, oscillations developed during diastolic depolarization. These oscillations were frequency dependent in two respects: 1) at slower rates the oscillations remained constant during the drive, the actual magnitude being proportional to the driving rate; 2) at rate of 60/min or more, the oscillations increased in size with each successive beat. Fast rhythms were initiated by a progressive acceleration of the pacemaker potential or abruptly by an extrasystole. When spontaneous activity ceased, the membrane increased slowly toward the control value. We conclude that digitalis increases the frequency of discharge of Purkinje fibers 1) by enhancing diastolic depolarization when the rate of discharge is slow; 2) by developing a new current which modifies diastolic depolarization when diastole is sufficiently short; and 3) by means of the potassium plateau current when the rate of spontaneous discharge is fast. Whether one or more of these mechanisms are operational in affecting Purkinje fiber automaticity depends critically on the rate of discharge of the fibers.", "contents": "On the mechanisms underlying digitalis toxicity in cardiac Purkinje fibers. The different mechanisms by which digitalis enhances pacemaker automaticity in canine Purkinje fibers has been studied under different conditions. Transmembrane potentials of quiescent, spontaneously active, or electrically driven fibers were recorded in the presence and absence of strophanthidin (10(-5)-10(-7) M). In quiescent fibers, strophanthidin caused the membrane potential to depolarize and to develop oscillations of progressively larger magnitude which were followed by spontaneous activity. In spontaneously active preparations strophanthidin enhanced the slope of diastolic depolarization and therefore the rate of discharge. In both cases, there was no evidence of oscillations during diastolic depolarization. A steepening of diastolic depolarizations without superimposed oscillations (and eventually also followed by spontaneous activity) was observed in preparations driven electrically at very slow rates. However, in fibers driven at faster rates (30/min or more) in the presence of ouabain, oscillations developed during diastolic depolarization. These oscillations were frequency dependent in two respects: 1) at slower rates the oscillations remained constant during the drive, the actual magnitude being proportional to the driving rate; 2) at rate of 60/min or more, the oscillations increased in size with each successive beat. Fast rhythms were initiated by a progressive acceleration of the pacemaker potential or abruptly by an extrasystole. When spontaneous activity ceased, the membrane increased slowly toward the control value. We conclude that digitalis increases the frequency of discharge of Purkinje fibers 1) by enhancing diastolic depolarization when the rate of discharge is slow; 2) by developing a new current which modifies diastolic depolarization when diastole is sufficiently short; and 3) by means of the potassium plateau current when the rate of spontaneous discharge is fast. Whether one or more of these mechanisms are operational in affecting Purkinje fiber automaticity depends critically on the rate of discharge of the fibers."} {"id": "PMID:1257582", "title": "Effects of ouabain and norepinephrine on the mechanical performance of the normal and failing heart of the myopathic hamster.", "content": "The effects of ouabain and norepinephrine on the mechanical efficiency of the normal and failing heart of the myopathic Syrian hamster were studied in a modified Langendorff preparation. Ouabain administration to the normal and failing heart caused a significant increase in heart work and energy utilization per beat with no significant change in the mechanical efficinecy of either heart. Norepinephrine caused a significant increase in heart work, energy utilization, and mechanical efficiency of the normal and failing heart. It was concluded that the isolated perfused hamster heart from normal and myopathic hamsters could provide a new model for the demonstration of the effect of cardiotonic agents on the mechanical performance of the heart.", "contents": "Effects of ouabain and norepinephrine on the mechanical performance of the normal and failing heart of the myopathic hamster. The effects of ouabain and norepinephrine on the mechanical efficiency of the normal and failing heart of the myopathic Syrian hamster were studied in a modified Langendorff preparation. Ouabain administration to the normal and failing heart caused a significant increase in heart work and energy utilization per beat with no significant change in the mechanical efficinecy of either heart. Norepinephrine caused a significant increase in heart work, energy utilization, and mechanical efficiency of the normal and failing heart. It was concluded that the isolated perfused hamster heart from normal and myopathic hamsters could provide a new model for the demonstration of the effect of cardiotonic agents on the mechanical performance of the heart."} {"id": "PMID:1257583", "title": "Glucose and palmitate uptake in the myocardium of isolated hearts from adrenalectomized cats.", "content": "Hearts from chronically adrenalectomized (ADX) cats deprived of any steroid support for 9-12 days were isolated and perfused in a Langendorff apparatus at a constant pressure of 95 mm Hg. The perfusion medium was Krebs-Henseleit buffer with either 10 mM glucose or 0.4 mM palmitate complexed to 3 percent albumin. Labeled 14C substrate was used and the transient rate of glucose and palmitate uptake was measured. Oxygen consumption and [14C] palmitate incorporation into CO2, and heart lipids were also measured. ADX hearts showed an enhanced glucose uptake rate compared with controls, 65 +/- 11.3 mumoles/gm to 16.2 +/- 6. However, the qO2 was not significantly different from control hearts. Palmitate uptake, O2 consumption, and 14CO2 were significantly lower in ADX hearts perfused with fatty acid as the energy substrate. Fatty acid uptake decreased from 9.7 +/- 1.0 to 3.6 +/- 1.1 and lipid fractions in the heart showed significant decreases in [14C] palmitate incorporated into triglycerides (p less than 0.001) and monoglycerides (p less than 0.01). The ADX heart does not appear to have any impairment to glucose uptake but does show an impairment to fatty acid uptake. Because the heart uses lipid as the primary energy source, the impairment probably is not the primary factor responsible for cardiac failure in adrenal insufficiency because of its capability of using other available substrates for energy.", "contents": "Glucose and palmitate uptake in the myocardium of isolated hearts from adrenalectomized cats. Hearts from chronically adrenalectomized (ADX) cats deprived of any steroid support for 9-12 days were isolated and perfused in a Langendorff apparatus at a constant pressure of 95 mm Hg. The perfusion medium was Krebs-Henseleit buffer with either 10 mM glucose or 0.4 mM palmitate complexed to 3 percent albumin. Labeled 14C substrate was used and the transient rate of glucose and palmitate uptake was measured. Oxygen consumption and [14C] palmitate incorporation into CO2, and heart lipids were also measured. ADX hearts showed an enhanced glucose uptake rate compared with controls, 65 +/- 11.3 mumoles/gm to 16.2 +/- 6. However, the qO2 was not significantly different from control hearts. Palmitate uptake, O2 consumption, and 14CO2 were significantly lower in ADX hearts perfused with fatty acid as the energy substrate. Fatty acid uptake decreased from 9.7 +/- 1.0 to 3.6 +/- 1.1 and lipid fractions in the heart showed significant decreases in [14C] palmitate incorporated into triglycerides (p less than 0.001) and monoglycerides (p less than 0.01). The ADX heart does not appear to have any impairment to glucose uptake but does show an impairment to fatty acid uptake. Because the heart uses lipid as the primary energy source, the impairment probably is not the primary factor responsible for cardiac failure in adrenal insufficiency because of its capability of using other available substrates for energy."} {"id": "PMID:1257584", "title": "Radiation-induced enzyme efflux from rat heart: sedentary animals.", "content": "Serum levels of lactate dehydrogenase, creatine kinase, and glutamate oxaloacetate transaminase show initial elevations within 12 hr of exposure to 2,000 rads of gamma-radiation to the thoracic region of rats. Significant decreases in heart muscle homogenate levels of these enzymes parallel initial elevations in the serum and may suggest that enhanced leakage of enzymes is a consequence of radiation injury to heart muscle. Insignificant alterations in mitochondrial glutamate oxaloacetate transaminase levels after exposure indicate that in vivo injury to the mitochondria from therapeutic levels of gamma-radiation is questionable. The results support the contention that ionizing radiation instigates alterations in the dynamic permeability of membranes, allowing leakage of biologically active material out of the injured cell.", "contents": "Radiation-induced enzyme efflux from rat heart: sedentary animals. Serum levels of lactate dehydrogenase, creatine kinase, and glutamate oxaloacetate transaminase show initial elevations within 12 hr of exposure to 2,000 rads of gamma-radiation to the thoracic region of rats. Significant decreases in heart muscle homogenate levels of these enzymes parallel initial elevations in the serum and may suggest that enhanced leakage of enzymes is a consequence of radiation injury to heart muscle. Insignificant alterations in mitochondrial glutamate oxaloacetate transaminase levels after exposure indicate that in vivo injury to the mitochondria from therapeutic levels of gamma-radiation is questionable. The results support the contention that ionizing radiation instigates alterations in the dynamic permeability of membranes, allowing leakage of biologically active material out of the injured cell."} {"id": "PMID:1257585", "title": "Effects of ischemia and reperfusion on myocardial uptake of tritiated digoxin.", "content": "The effect of coronary reperfusion on the uptake of cardiac glycosides by ischemic myocardium was studied in 17 open chested dogs undergoing anterior wall infarction produced by snaring confluent branches of the left coronary system. Epicardial electrograms delineated ischemic zones of S-T elevation, border, and nonischemic zones. Animals were reperfused by snare release 1, 2, and 6 hr after occlusion. After 15 min of reperfusion, 1.0 mg of [3H] digoxin was given intravenously, and 2 hr later the hearts were excised and endocardial (endo) and epicardial (epi) samples from each zone were analyzed for [3H] digoxin concentration. In five dogs occluded for 1 hr and reperfused, [3H] digoxin uptake was comparable in endo and epi layers of all three zones. In six dogs reperfused after 2 hr of occlusion, mean (+/-S.E.) [3H] digoxin concentrations (nanograms per gm) were significantly reduced by 54 percent in endo (111 +/-18) and 35 percent in epi (151 +/- 23) layers of the ischemic zone as compared with the mean nonischemic concentration (endo249 +/- 34; epi 239 +/- 34). Border zone endo and epi [3H] digoxin uptake was reduced by 21 and 17 percent, respectively. In six dogs reperfused after 6 hr of occlusion, [3H] digoxin uptake in the ischemic zone was markedly reduced by 85 percent in endo (34 +/- 4) and 60 percent in epi (86 +/- 12) layers as compared with the nonischemic concentration (endo 232 +/- 19; epi 217 +/- 15). Border zone uptake was decreased by 54 percent in endo and 38 percent in epi regions. We conclude that coronary reperfusion between 2 and 6 hr of coronary occlusion is associated with markedly reduced myocardial digoxin uptake, more pronounced in subendocardial regions of ischemic tissue. This alteration in digoxin binding by reperfused ischemic myocardium is consistent with ischemia-induced structural or functional alterations in the putative digitalis receptor, (Na++K+)-ATPase.", "contents": "Effects of ischemia and reperfusion on myocardial uptake of tritiated digoxin. The effect of coronary reperfusion on the uptake of cardiac glycosides by ischemic myocardium was studied in 17 open chested dogs undergoing anterior wall infarction produced by snaring confluent branches of the left coronary system. Epicardial electrograms delineated ischemic zones of S-T elevation, border, and nonischemic zones. Animals were reperfused by snare release 1, 2, and 6 hr after occlusion. After 15 min of reperfusion, 1.0 mg of [3H] digoxin was given intravenously, and 2 hr later the hearts were excised and endocardial (endo) and epicardial (epi) samples from each zone were analyzed for [3H] digoxin concentration. In five dogs occluded for 1 hr and reperfused, [3H] digoxin uptake was comparable in endo and epi layers of all three zones. In six dogs reperfused after 2 hr of occlusion, mean (+/-S.E.) [3H] digoxin concentrations (nanograms per gm) were significantly reduced by 54 percent in endo (111 +/-18) and 35 percent in epi (151 +/- 23) layers of the ischemic zone as compared with the mean nonischemic concentration (endo249 +/- 34; epi 239 +/- 34). Border zone endo and epi [3H] digoxin uptake was reduced by 21 and 17 percent, respectively. In six dogs reperfused after 6 hr of occlusion, [3H] digoxin uptake in the ischemic zone was markedly reduced by 85 percent in endo (34 +/- 4) and 60 percent in epi (86 +/- 12) layers as compared with the nonischemic concentration (endo 232 +/- 19; epi 217 +/- 15). Border zone uptake was decreased by 54 percent in endo and 38 percent in epi regions. We conclude that coronary reperfusion between 2 and 6 hr of coronary occlusion is associated with markedly reduced myocardial digoxin uptake, more pronounced in subendocardial regions of ischemic tissue. This alteration in digoxin binding by reperfused ischemic myocardium is consistent with ischemia-induced structural or functional alterations in the putative digitalis receptor, (Na++K+)-ATPase."} {"id": "PMID:1257586", "title": "Effects of calcium-free perfusion on excitation-contraction coupling in heart and skeletal muscle.", "content": "Interventricular septa and semimembranosus accessorius muscles (SMA) from the guinea pig and frog gastrocnemius (FG) muscles were vascularly perfused and isolated for mechanical and radioisotope flux measurements. Since calcium deprivation causes progressive electrical inexcitability, 100 muM La was included in all calcium-free solutions (0-Ca, 100-La) to stabilize the membrane. Perfusion of ventricular septa with such solutions resulted in tension (P) and dP/dt declines with half-times (t 1/2) = 11 sec, similar to the most rapid phase of 45Ca efflux. In contrast, the major component of tension decline during 0-Ca, 100-La perfusion of the SMA and FG muscles was much slower (t 1/2 =33 min). The rate of the slow component of 45Ca efflux from the SMA and FG muscles was essentially identical with the rate of the major tension decline. Significant tension (10-16 percent) was still present in these perfused skeletal muscles after 1-2 hr of 0-Ca, 100-La perfusion. Subsequent addition of La (200 muM total La) did not change the slope of P decline significantly for an additional 30-45 min. Addition of up to 2 mM EGTA after 30 min 0-Ca perfusion (calculated extracellular [Ca2+] less than 3x10(-9) M) altered but slightly the rate of P decline. These experiments emphasize the difference in the source of contractile Ca in heart and skeletal muscle and make it unlikely that there is a physiological \"trigger\" Ca for excitation-contraction (E-C) coupling in these muscles.", "contents": "Effects of calcium-free perfusion on excitation-contraction coupling in heart and skeletal muscle. Interventricular septa and semimembranosus accessorius muscles (SMA) from the guinea pig and frog gastrocnemius (FG) muscles were vascularly perfused and isolated for mechanical and radioisotope flux measurements. Since calcium deprivation causes progressive electrical inexcitability, 100 muM La was included in all calcium-free solutions (0-Ca, 100-La) to stabilize the membrane. Perfusion of ventricular septa with such solutions resulted in tension (P) and dP/dt declines with half-times (t 1/2) = 11 sec, similar to the most rapid phase of 45Ca efflux. In contrast, the major component of tension decline during 0-Ca, 100-La perfusion of the SMA and FG muscles was much slower (t 1/2 =33 min). The rate of the slow component of 45Ca efflux from the SMA and FG muscles was essentially identical with the rate of the major tension decline. Significant tension (10-16 percent) was still present in these perfused skeletal muscles after 1-2 hr of 0-Ca, 100-La perfusion. Subsequent addition of La (200 muM total La) did not change the slope of P decline significantly for an additional 30-45 min. Addition of up to 2 mM EGTA after 30 min 0-Ca perfusion (calculated extracellular [Ca2+] less than 3x10(-9) M) altered but slightly the rate of P decline. These experiments emphasize the difference in the source of contractile Ca in heart and skeletal muscle and make it unlikely that there is a physiological \"trigger\" Ca for excitation-contraction (E-C) coupling in these muscles."} {"id": "PMID:1257591", "title": "Drugs and punished responding VI: body weight as a determinant of drug effects.", "content": "Pigeons were rewarded with grain for pecking a key under a fixed-interval schedule of food presentation. After responding stabilized, each key-peck produced a 3.5 mA electric shock, about 50 msec in duration. Dose-effect curves for pentobarbital, d-amphetamine and chlordiazepoxide on punished responding were determined in these pigeons when their body weights were adjusted to 70%, 90% or 100% of their free-feeding weights. The lower the body weight, the higher the rate of punished responding before drugs were given. Pentobarbital increased punished responding in all three body weights, but it produced the largest increases in punished responding over the widest dose range when the body weight was maintained at 90% of the free-feeding weight. Chlordiazepoxide also tended to produce rate increases at all three body weights, but d-amphetamine increased the rate only when the birds were maintained at 100% of their free-feeding weights.", "contents": "Drugs and punished responding VI: body weight as a determinant of drug effects. Pigeons were rewarded with grain for pecking a key under a fixed-interval schedule of food presentation. After responding stabilized, each key-peck produced a 3.5 mA electric shock, about 50 msec in duration. Dose-effect curves for pentobarbital, d-amphetamine and chlordiazepoxide on punished responding were determined in these pigeons when their body weights were adjusted to 70%, 90% or 100% of their free-feeding weights. The lower the body weight, the higher the rate of punished responding before drugs were given. Pentobarbital increased punished responding in all three body weights, but it produced the largest increases in punished responding over the widest dose range when the body weight was maintained at 90% of the free-feeding weight. Chlordiazepoxide also tended to produce rate increases at all three body weights, but d-amphetamine increased the rate only when the birds were maintained at 100% of their free-feeding weights."} {"id": "PMID:1257592", "title": "Absence of collagen stimulating factors for L929 cells in granulation tissue extracts.", "content": "We have attempted to find collagen synthesis stimulating activity in polyvinyl sponge granulation tissue extracts and inflammatory fluid. The cells studied in culture were mouse L929 cells grown in monolayers. A prior study by another group reported such factors to be present in healing wound extracts and in extracts of CHHl3 injured liver. We have been unable to find such stimulating activity for L929 cells in granuloma tissue fluid. In addition we have examined the procedures used by the prior group and have found major problems in their methodology which are discussed below.", "contents": "Absence of collagen stimulating factors for L929 cells in granulation tissue extracts. We have attempted to find collagen synthesis stimulating activity in polyvinyl sponge granulation tissue extracts and inflammatory fluid. The cells studied in culture were mouse L929 cells grown in monolayers. A prior study by another group reported such factors to be present in healing wound extracts and in extracts of CHHl3 injured liver. We have been unable to find such stimulating activity for L929 cells in granuloma tissue fluid. In addition we have examined the procedures used by the prior group and have found major problems in their methodology which are discussed below."} {"id": "PMID:1257593", "title": "Anticoagulant activity of a naphthoquinone analog of vitamin K and an inhibitor of coenzyme Q10- enzyme systems.", "content": "Synthetic 2-hydroxy-3-h-dodecylmercapto-1,4-naphthoquinone is an analog of both vitamin K1 and coenzyme Q10. This naphthoquinone analog is an effective inhibitor of coenzyme Q10-enzymes of mammalian mitochondria, which are components of electron transfer mechanisms of respiration and coupled oxidative phosphorylation. This analog increased the prothrombin time in rats when it was administered orally or parenterally. Vitamin K1 reversed the prothrombin time increase, but that form of coenzyme Q, hexahydrocoenzyme Q4, which has the same phytyl side chain as vitamin K1, did not reverse the increase, constituting the biological differentiation between vitamin K and coenzyem Q. Two benzoquinone analogs of coenzyme Q10, 5-n-octadecylmercapto-2,3-dimethoxy-1,4-benzoquinone and 5-beta-naphthylmercapto-2,3-dimethoxy-1,4-benzoquinone, the latter being a strong inhibitor of coenzyme Q10-enzymes, did not increase the prothrombin time under comparable conditions.", "contents": "Anticoagulant activity of a naphthoquinone analog of vitamin K and an inhibitor of coenzyme Q10- enzyme systems. Synthetic 2-hydroxy-3-h-dodecylmercapto-1,4-naphthoquinone is an analog of both vitamin K1 and coenzyme Q10. This naphthoquinone analog is an effective inhibitor of coenzyme Q10-enzymes of mammalian mitochondria, which are components of electron transfer mechanisms of respiration and coupled oxidative phosphorylation. This analog increased the prothrombin time in rats when it was administered orally or parenterally. Vitamin K1 reversed the prothrombin time increase, but that form of coenzyme Q, hexahydrocoenzyme Q4, which has the same phytyl side chain as vitamin K1, did not reverse the increase, constituting the biological differentiation between vitamin K and coenzyem Q. Two benzoquinone analogs of coenzyme Q10, 5-n-octadecylmercapto-2,3-dimethoxy-1,4-benzoquinone and 5-beta-naphthylmercapto-2,3-dimethoxy-1,4-benzoquinone, the latter being a strong inhibitor of coenzyme Q10-enzymes, did not increase the prothrombin time under comparable conditions."} {"id": "PMID:1257594", "title": "Antigenicity of inactivated swine influenza virus concentrated by centrifugation.", "content": "Swine influenza virus grown in fertile chicken eggs was inactivated with a 1:4000 dilution of formalin for three days. Centrifugation at 47,000 g for 1-3 hours concentrated the viral particles. Reconstitution to 1/10 the original volume for use as a vaccine resulted in a product having an HA titer of 1:64 to 1:512. Two doses of 4 ml given three weeks apart resulted in a serologic response in three of six gilts of breeding age. Experimental challenge of two vaccinated and two control gilts to swine influenze virus showed that vaccinated gilts did not react by production of a marked HI antibody response when compared to unvaccinated gilts.", "contents": "Antigenicity of inactivated swine influenza virus concentrated by centrifugation. Swine influenza virus grown in fertile chicken eggs was inactivated with a 1:4000 dilution of formalin for three days. Centrifugation at 47,000 g for 1-3 hours concentrated the viral particles. Reconstitution to 1/10 the original volume for use as a vaccine resulted in a product having an HA titer of 1:64 to 1:512. Two doses of 4 ml given three weeks apart resulted in a serologic response in three of six gilts of breeding age. Experimental challenge of two vaccinated and two control gilts to swine influenze virus showed that vaccinated gilts did not react by production of a marked HI antibody response when compared to unvaccinated gilts."} {"id": "PMID:1257595", "title": "Increased lung compliance in mice exposed to sulfur dioxide.", "content": "Mice exposed 6-9 days to 40 ppm. SO2 lost 21% of body weight, but static lung compliance increased 37% (P less than or equal to 0.01). Slopes of saline volume-pressure curves increased 8% (non-sig) pointing to a decrease in surface tension rather than tissue elasticity. Alveolar stability, lung weight and lung wet/dry ratio decreased 2 to 6%, whereas trapped gas in-increased 17%, but none were statistically significant.", "contents": "Increased lung compliance in mice exposed to sulfur dioxide. Mice exposed 6-9 days to 40 ppm. SO2 lost 21% of body weight, but static lung compliance increased 37% (P less than or equal to 0.01). Slopes of saline volume-pressure curves increased 8% (non-sig) pointing to a decrease in surface tension rather than tissue elasticity. Alveolar stability, lung weight and lung wet/dry ratio decreased 2 to 6%, whereas trapped gas in-increased 17%, but none were statistically significant."} {"id": "PMID:1257596", "title": "Spectral characteristics of some metallo complexes of six-mercaptopurine.", "content": "Absorption spectra from 400-250 nm were obtained for 6-mercaptopurine (6-MP) and its Bi, Pt, and Pd complexes. The peaks were all grouped in close proximity (+/-5nm) and the curves were similar. Under the conditions of this study, the purine chemistry of 6-MP does not appear to be appreciably altered as a result of the pure compound complexing with the Bi, Pt, or Pd metals.", "contents": "Spectral characteristics of some metallo complexes of six-mercaptopurine. Absorption spectra from 400-250 nm were obtained for 6-mercaptopurine (6-MP) and its Bi, Pt, and Pd complexes. The peaks were all grouped in close proximity (+/-5nm) and the curves were similar. Under the conditions of this study, the purine chemistry of 6-MP does not appear to be appreciably altered as a result of the pure compound complexing with the Bi, Pt, or Pd metals."} {"id": "PMID:1257597", "title": "Non-teratogenicity of prostaglandin F2alpha in the chick.", "content": "Chick embryos were exposed to prostaglandin F2alpha (10, 40 or 100 mug) at 48 and 72 hours incubation. Compared to the controls there was no significant increase in the incidence of embryonic death and developmental defects.", "contents": "Non-teratogenicity of prostaglandin F2alpha in the chick. Chick embryos were exposed to prostaglandin F2alpha (10, 40 or 100 mug) at 48 and 72 hours incubation. Compared to the controls there was no significant increase in the incidence of embryonic death and developmental defects."} {"id": "PMID:1257598", "title": "Mitotic changes in neuroblastoma transplanted into denervated host tissue.", "content": "Tumors were transplanted to denervated and innervated hind limbs of A/J mice and grown for 5 days in all groups. The host tissues were denervated by femoral and sciatic nerve section 4 days prior to tumor implantation. Dnervation of host tissues resulted in a significant reduction in tumor mitotic rate as assessed by mitotic counts in the histological sections. Neurotrophic factors may thus be an additional feature of the host-tumor environment.", "contents": "Mitotic changes in neuroblastoma transplanted into denervated host tissue. Tumors were transplanted to denervated and innervated hind limbs of A/J mice and grown for 5 days in all groups. The host tissues were denervated by femoral and sciatic nerve section 4 days prior to tumor implantation. Dnervation of host tissues resulted in a significant reduction in tumor mitotic rate as assessed by mitotic counts in the histological sections. Neurotrophic factors may thus be an additional feature of the host-tumor environment."} {"id": "PMID:1257599", "title": "The metabolism of L-ethionine in rats fed alpha-naphthyl isothiocyanate.", "content": "L-[ethyl-2-14C] ethionine was administered in a single dose to rats fed a diet containing 0.10% alpha-naththyl isothiocyanate for a period of time between 6 and 99 days. Ethionine metabolites excreted into urine were investigated as a function of induced pathologic changes in the liver. A short-time exposure (6 and 14 days) to alpha-naththyl isothiocyanate increased the excretion of free ethionine and S-adenosylethionine at the expense of total ethionine sulfoxide. With the extended feeding period the excretion of total ethionine sulfoxide became normalized while the excretion of free ethionine and S-adenosylethionine decreased. The acetylated fraction of ethionine sulfoxide decreased rapidly and reached a minimum in 14 days of feeding. This fraction subsequently started to increase, but did not reach the values obtained in normal rats.", "contents": "The metabolism of L-ethionine in rats fed alpha-naphthyl isothiocyanate. L-[ethyl-2-14C] ethionine was administered in a single dose to rats fed a diet containing 0.10% alpha-naththyl isothiocyanate for a period of time between 6 and 99 days. Ethionine metabolites excreted into urine were investigated as a function of induced pathologic changes in the liver. A short-time exposure (6 and 14 days) to alpha-naththyl isothiocyanate increased the excretion of free ethionine and S-adenosylethionine at the expense of total ethionine sulfoxide. With the extended feeding period the excretion of total ethionine sulfoxide became normalized while the excretion of free ethionine and S-adenosylethionine decreased. The acetylated fraction of ethionine sulfoxide decreased rapidly and reached a minimum in 14 days of feeding. This fraction subsequently started to increase, but did not reach the values obtained in normal rats."} {"id": "PMID:1257600", "title": "Methaqualone metabolism by rat liver microsomes.", "content": "A rat hepatic microsomal system has been established which metabolizes methaqualone. The microsomes are obtained from livers of rats treated with phenobarbital. The methaqualone is dissolved in polyethylene glycol-200 prior to addition to the incubation mixture. A comparison is made between the metabolites obtained in this in vitro system and metabolites obtained from urines of phenobarbital treated rats injected with methaqualone. The same two and sometimes three metabolites, as determined by thin layer and gas liquid chromatography, were found in both the complete microsomal incubation system and the urines.", "contents": "Methaqualone metabolism by rat liver microsomes. A rat hepatic microsomal system has been established which metabolizes methaqualone. The microsomes are obtained from livers of rats treated with phenobarbital. The methaqualone is dissolved in polyethylene glycol-200 prior to addition to the incubation mixture. A comparison is made between the metabolites obtained in this in vitro system and metabolites obtained from urines of phenobarbital treated rats injected with methaqualone. The same two and sometimes three metabolites, as determined by thin layer and gas liquid chromatography, were found in both the complete microsomal incubation system and the urines."} {"id": "PMID:1257601", "title": "Metabolism of 5-(p-toluyl)-5-ethylbarbituric acid and 5-(p-toluyl)-5-phenylhydantoin in the isolated perfused rat liver.", "content": "The primary route of metabolism of 5-(p-toluyl)-5-ethylbarbituric acid (TEBA) and 5-(p-toluyl)-5-phenylhydantoin (MPPH) in the isolated perfused rat liver is oxidation of the aromatic methyl group either to a primary alcohol which is then conjugated with glucuronic acid and excreted in the bile (MPPH only) or to the carboxylic acid which is excreted free in the bile (both TEBA and MPPH). All metabolites were identified by previously described permethylation and GC-MS techniques.", "contents": "Metabolism of 5-(p-toluyl)-5-ethylbarbituric acid and 5-(p-toluyl)-5-phenylhydantoin in the isolated perfused rat liver. The primary route of metabolism of 5-(p-toluyl)-5-ethylbarbituric acid (TEBA) and 5-(p-toluyl)-5-phenylhydantoin (MPPH) in the isolated perfused rat liver is oxidation of the aromatic methyl group either to a primary alcohol which is then conjugated with glucuronic acid and excreted in the bile (MPPH only) or to the carboxylic acid which is excreted free in the bile (both TEBA and MPPH). All metabolites were identified by previously described permethylation and GC-MS techniques."} {"id": "PMID:1257602", "title": "Effects of chronic administration of polybrominated biphenyls on parameters associated with hepatic drug metabolism.", "content": "Parameters relating to hepatic microsomal drug metabolism were measured in vitro following 2 weeks exposure of rats to polybrominated biphenyls (PBB) as a dietary supplement at 4.69, 18.75, 75 and 300 ppm. The mixture of PBB was a potent inducer of hepatic microsomal drug metabolism. The pattern of induction seen after PBB exposure was compared with that produced by phenobarbital and 3-methyl-cholanthrene and the pattern of induction observed shared similarities with both of these agents.", "contents": "Effects of chronic administration of polybrominated biphenyls on parameters associated with hepatic drug metabolism. Parameters relating to hepatic microsomal drug metabolism were measured in vitro following 2 weeks exposure of rats to polybrominated biphenyls (PBB) as a dietary supplement at 4.69, 18.75, 75 and 300 ppm. The mixture of PBB was a potent inducer of hepatic microsomal drug metabolism. The pattern of induction seen after PBB exposure was compared with that produced by phenobarbital and 3-methyl-cholanthrene and the pattern of induction observed shared similarities with both of these agents."} {"id": "PMID:1257603", "title": "Treatment with o,p'-DDD (mitotane) decreased cytochrome P-450, heme, and microsomal protein content in the dog adrenal cortex in vivo.", "content": "Treatment with o,p'-DDD, at a does which markedly inhibits steroidogenesis (60 mg/kg, intravenously), significantly decreased adrenal mitochondrial and microsomal \"P-450\" and microsomal protein contnet 34%, 55%, and 35% respectively, within 3 hours. The reduction of cytochrome P-450 content was accompanied by decrease in heme content, which explains the apparent loss of cytochrome P-450. This action provides a possible explanation for the inhibition of steroidogenesis caused by o,p'-DDD, and indicates that o,p'-DDD initiates a very destructive process in the dog adrenal cortex.", "contents": "Treatment with o,p'-DDD (mitotane) decreased cytochrome P-450, heme, and microsomal protein content in the dog adrenal cortex in vivo. Treatment with o,p'-DDD, at a does which markedly inhibits steroidogenesis (60 mg/kg, intravenously), significantly decreased adrenal mitochondrial and microsomal \"P-450\" and microsomal protein contnet 34%, 55%, and 35% respectively, within 3 hours. The reduction of cytochrome P-450 content was accompanied by decrease in heme content, which explains the apparent loss of cytochrome P-450. This action provides a possible explanation for the inhibition of steroidogenesis caused by o,p'-DDD, and indicates that o,p'-DDD initiates a very destructive process in the dog adrenal cortex."} {"id": "PMID:1257604", "title": "New method for detecting and quantitating pharmacokinetic drug-drug interactions applied to ethanol-propranolol.", "content": "A novel method for detecting and quantitating pharmacokinetic drug-drug interactions is described. The method involves perturbation of an existing steady-state whole blood (or plasma) concentration of one drug by the other drug. The method would allow differentiation of \"pharmacokinetic\" drug interactions from \"pharmacologic\" interactions. It is shown that a bolus intravenous injection of propranolol reduced a steady-state arterial blood concentration of ethyl alcohol by 26% in the cat.", "contents": "New method for detecting and quantitating pharmacokinetic drug-drug interactions applied to ethanol-propranolol. A novel method for detecting and quantitating pharmacokinetic drug-drug interactions is described. The method involves perturbation of an existing steady-state whole blood (or plasma) concentration of one drug by the other drug. The method would allow differentiation of \"pharmacokinetic\" drug interactions from \"pharmacologic\" interactions. It is shown that a bolus intravenous injection of propranolol reduced a steady-state arterial blood concentration of ethyl alcohol by 26% in the cat."} {"id": "PMID:1257605", "title": "Excretion, distribution and metabolic fate of 3H-alpha-chaconine.", "content": "3H-alpha-Chaconine was poorly absorbed from the gastrointestinal tract and rapidly excreted in feces when administered orally to male rats. Intraperitoneal administration of low doses (5 to 10 mg/kg) resulted in urinary and fecal excretion of metabolites, and probably involved biliary excretion. High, toxic, intraperitoneal doses (15 to 25 mg/kg) depressed fecal and urinary elimination, and resulted in accumulation of tritium in various tissues. The major metabolite appeared to be the aglycone, solanidine. Alpha-chaconine is very similar to alpha-solanine in its elimination by and distribution in tissues of rats.", "contents": "Excretion, distribution and metabolic fate of 3H-alpha-chaconine. 3H-alpha-Chaconine was poorly absorbed from the gastrointestinal tract and rapidly excreted in feces when administered orally to male rats. Intraperitoneal administration of low doses (5 to 10 mg/kg) resulted in urinary and fecal excretion of metabolites, and probably involved biliary excretion. High, toxic, intraperitoneal doses (15 to 25 mg/kg) depressed fecal and urinary elimination, and resulted in accumulation of tritium in various tissues. The major metabolite appeared to be the aglycone, solanidine. Alpha-chaconine is very similar to alpha-solanine in its elimination by and distribution in tissues of rats."} {"id": "PMID:1257606", "title": "Disposition of nicotine in the rat after intravenous administration.", "content": "The pharmacokinetics of 14C-labeled nicotine were studied in male Fischer-344 rats following the i.v. administration of a single 0.8 mg/kg dose. Serial blood samples were collected and the nicotine in plasma was separated from its metabolites by TLC. The levels of radioactivity corresponding to nicotine, cotinine, and polar metabolites remaining at the origin of the chromatogram were determined by liquid scintillation counting. Plasma nicotine concentration was characterized by a biexponential decay with a mean biologic half-life (t1/2) of 0.96 hrs, a large apparent volume of distribution (5.67 L/kg) and total body clearance (4.04 L/hr/kg). Maximum plasma concentration of cotinine was reached within 1 1/2 hrs post-nicotine administration, followed by a monoexponential decline with a mean t1/2 of 6.4 hrs. The plasma concentrations of origin activity rose to maximum levels within 30 minutes and declined slowly in a biexponential fashion with a mean t1/2 of 23.2 hrs. It appears, therefore, that while nicotine is rapidly eliminated, its metabolites persist in the plasma a long time after its administration.", "contents": "Disposition of nicotine in the rat after intravenous administration. The pharmacokinetics of 14C-labeled nicotine were studied in male Fischer-344 rats following the i.v. administration of a single 0.8 mg/kg dose. Serial blood samples were collected and the nicotine in plasma was separated from its metabolites by TLC. The levels of radioactivity corresponding to nicotine, cotinine, and polar metabolites remaining at the origin of the chromatogram were determined by liquid scintillation counting. Plasma nicotine concentration was characterized by a biexponential decay with a mean biologic half-life (t1/2) of 0.96 hrs, a large apparent volume of distribution (5.67 L/kg) and total body clearance (4.04 L/hr/kg). Maximum plasma concentration of cotinine was reached within 1 1/2 hrs post-nicotine administration, followed by a monoexponential decline with a mean t1/2 of 6.4 hrs. The plasma concentrations of origin activity rose to maximum levels within 30 minutes and declined slowly in a biexponential fashion with a mean t1/2 of 23.2 hrs. It appears, therefore, that while nicotine is rapidly eliminated, its metabolites persist in the plasma a long time after its administration."} {"id": "PMID:1257607", "title": "The human metabolism of caffeine to theophylline.", "content": "Theophylline peak plasma concentration of over 170 ng/ml average was observed when 300 mg of caffeine, equivalent to 2-3 cups of coffee, was administered to humans. This peak level was not observed until at least 7 hr post administration. Accumulation of caffeine, with its subsequent metabolism to theophylline, in patients, who consume average quantities of caffeine-containing beverages relative to those patients who avoid such drinks could interfere with bioavailability studies in normal volunteers. However, it may account for only a small portion of the variable clinical effects associated with aminophylline administration.", "contents": "The human metabolism of caffeine to theophylline. Theophylline peak plasma concentration of over 170 ng/ml average was observed when 300 mg of caffeine, equivalent to 2-3 cups of coffee, was administered to humans. This peak level was not observed until at least 7 hr post administration. Accumulation of caffeine, with its subsequent metabolism to theophylline, in patients, who consume average quantities of caffeine-containing beverages relative to those patients who avoid such drinks could interfere with bioavailability studies in normal volunteers. However, it may account for only a small portion of the variable clinical effects associated with aminophylline administration."} {"id": "PMID:1257608", "title": "Identification of a methylated catechol metabolite of glutethimide (Doriden) in human urine.", "content": "A new metabolite of glutethimide has been isolated and identified as a methylated catechol. Gas chromatographic parameters as well as mass spectral data are presented which clearly reveal this metabolite to be present in enzymatically hydrolyzed urine of patients severely intoxicated by the parent drug.", "contents": "Identification of a methylated catechol metabolite of glutethimide (Doriden) in human urine. A new metabolite of glutethimide has been isolated and identified as a methylated catechol. Gas chromatographic parameters as well as mass spectral data are presented which clearly reveal this metabolite to be present in enzymatically hydrolyzed urine of patients severely intoxicated by the parent drug."} {"id": "PMID:1257609", "title": "A comparison of 6,7-dihydroxytetrahydroisoquinoline, salsolinol and tetrahydropapaveroline as inhibitors of monoamine oxidase within the adrenergic nerve plexus of the isolated mouse atrium.", "content": "Three dopamine-derived tetrahydroisoquinolines (TIQs) were tested for their ability to inhibit monoamine oxidase (MAO) within the adrenergic plexus of atria from reserpinized mice. Inhibition of MAO was shown by improved accumulation of 3H-norepinephrine with a concomitant decrease in 3H-deaminated catechols. Salsolinol was less potent than 6,7-dihydroxy-TIQ as a MAO inhibitor. Tetrahydropapaveroline did not appear to inhibit MAO in this system.", "contents": "A comparison of 6,7-dihydroxytetrahydroisoquinoline, salsolinol and tetrahydropapaveroline as inhibitors of monoamine oxidase within the adrenergic nerve plexus of the isolated mouse atrium. Three dopamine-derived tetrahydroisoquinolines (TIQs) were tested for their ability to inhibit monoamine oxidase (MAO) within the adrenergic plexus of atria from reserpinized mice. Inhibition of MAO was shown by improved accumulation of 3H-norepinephrine with a concomitant decrease in 3H-deaminated catechols. Salsolinol was less potent than 6,7-dihydroxy-TIQ as a MAO inhibitor. Tetrahydropapaveroline did not appear to inhibit MAO in this system."} {"id": "PMID:1257610", "title": "Is the serotonin binding protein (SBP) a soluble storage form for serotonin?", "content": "The binding of serotonin to a soluble, high affinity binding protein (SBP) present in synaptosomes and assoicated with serotonergic tracts, has now been studied for the effect of drugs and, in particular, drugs interacting with contractile proteins. Vincristine, vinblastine, and cytochalasin B were found to cause 50% inhibition of serotonin binding to SBP at 1.5 X 10(-6)M, 7.5 X 10(-6)M and 50 X 10(-6)M, respectively. Colchicine did not affect the binding at 1 X 10(-3)M. When vinblastine was injected intraventricularly, the binding capacity of SBP isolated from brain 20 and 26 hours after injection was decreased 42% and 60% respectively. It is concluded that SBP is an actin-like contractile protein, distinct from microtubulin, and not associated with membranes. The storage of serotonin through binding to a protein with such properties suggests that this compartment is in some way involved in the translocation or transfer of serotonin from one part of the cell to another.", "contents": "Is the serotonin binding protein (SBP) a soluble storage form for serotonin? The binding of serotonin to a soluble, high affinity binding protein (SBP) present in synaptosomes and assoicated with serotonergic tracts, has now been studied for the effect of drugs and, in particular, drugs interacting with contractile proteins. Vincristine, vinblastine, and cytochalasin B were found to cause 50% inhibition of serotonin binding to SBP at 1.5 X 10(-6)M, 7.5 X 10(-6)M and 50 X 10(-6)M, respectively. Colchicine did not affect the binding at 1 X 10(-3)M. When vinblastine was injected intraventricularly, the binding capacity of SBP isolated from brain 20 and 26 hours after injection was decreased 42% and 60% respectively. It is concluded that SBP is an actin-like contractile protein, distinct from microtubulin, and not associated with membranes. The storage of serotonin through binding to a protein with such properties suggests that this compartment is in some way involved in the translocation or transfer of serotonin from one part of the cell to another."} {"id": "PMID:1257611", "title": "The effect of various phenothiazines and tricyclic antidepressants on the accumulation and release of (3H)norepinephrine and (3H)5-hydroxytryptamine in slices of rat occipital cortex.", "content": "The effects of various structurally related tricyclic antidepressants and phenothiazines on the accumulation of (3H)-5-hydroxytryptamine, [(3H)5-HT] and (3H)norepinephrine [(3H)NE] and on the release of previously accumulated (3H)5-HT and (3H)NE were determined in slices of rat occipital cortex. Results may be summarized as follows: 1) Each compound was a better inhibitor of accumulation [both of (3H)5-HT and (3H)NE] than it was a releasing agent. 2) The hydroxylation of tricyclic antidepressants made little difference in the potencies of the compounds as inhibitors of both (3H)NE and (3H)5-HT accumulation. 3) The N-dimethylated phenothiazines and tricyclics (tertiary amines) were better inhibitors of (3H)5-HT accumulation than their corresponding secondary amines. 4) The change from a dimethylene bridge in the tricyclic antidepressants to an S atom in the phenothiazines led to a considerable decrease in the potency of the compounds as inhibitors of (3H)5-HT accumulation, but made less difference in the (3H)NE accumulation system.", "contents": "The effect of various phenothiazines and tricyclic antidepressants on the accumulation and release of (3H)norepinephrine and (3H)5-hydroxytryptamine in slices of rat occipital cortex. The effects of various structurally related tricyclic antidepressants and phenothiazines on the accumulation of (3H)-5-hydroxytryptamine, [(3H)5-HT] and (3H)norepinephrine [(3H)NE] and on the release of previously accumulated (3H)5-HT and (3H)NE were determined in slices of rat occipital cortex. Results may be summarized as follows: 1) Each compound was a better inhibitor of accumulation [both of (3H)5-HT and (3H)NE] than it was a releasing agent. 2) The hydroxylation of tricyclic antidepressants made little difference in the potencies of the compounds as inhibitors of both (3H)NE and (3H)5-HT accumulation. 3) The N-dimethylated phenothiazines and tricyclics (tertiary amines) were better inhibitors of (3H)5-HT accumulation than their corresponding secondary amines. 4) The change from a dimethylene bridge in the tricyclic antidepressants to an S atom in the phenothiazines led to a considerable decrease in the potency of the compounds as inhibitors of (3H)5-HT accumulation, but made less difference in the (3H)NE accumulation system."} {"id": "PMID:1257613", "title": "The fate of intratracheally installed benzo(a)pyrene in the isolated perfused rat lung of both control and 20-methylcholanthrene pretreated rats.", "content": "The fate of intratracheally installed 3H-benzo(a)pyrene in the isolated perfused rat lung of both control and 20-methylcholanthrene pretreated rats and in perfusion fluid was studied. The covalent binding of benzo(a)pyrene metabolites in the lung tissue itself was greatly enhanced by 20-methylcholanthrene pretreatment of rats. Similarly, the appearance of unchanged 3H-benzo(a)pyrene in the perfusion fluid of 20-methylcholanthrene-lung was decreased as compared to control lung perfusion. This was accompanied with the increase of water-soluble metabolites of benzo(a)-pyrene in the perfusion fluid of 20-methylcholanthrene-lung. When analyzing the metabolite profile of benzo(a)-pyrene in the lungs, especially the phenols (7-fold) and 9,10-diols (5-fold) were found to be increased.", "contents": "The fate of intratracheally installed benzo(a)pyrene in the isolated perfused rat lung of both control and 20-methylcholanthrene pretreated rats. The fate of intratracheally installed 3H-benzo(a)pyrene in the isolated perfused rat lung of both control and 20-methylcholanthrene pretreated rats and in perfusion fluid was studied. The covalent binding of benzo(a)pyrene metabolites in the lung tissue itself was greatly enhanced by 20-methylcholanthrene pretreatment of rats. Similarly, the appearance of unchanged 3H-benzo(a)pyrene in the perfusion fluid of 20-methylcholanthrene-lung was decreased as compared to control lung perfusion. This was accompanied with the increase of water-soluble metabolites of benzo(a)-pyrene in the perfusion fluid of 20-methylcholanthrene-lung. When analyzing the metabolite profile of benzo(a)-pyrene in the lungs, especially the phenols (7-fold) and 9,10-diols (5-fold) were found to be increased."} {"id": "PMID:1257614", "title": "Effects of sound stimulus on gastric secretion and plasma corticosterone level in rats.", "content": "The effects of sound stimulus were studied on the gastric secretion in rats with chronically implanted cannulas. Attempts were made to correlate the changes in the secretion with those of the plasma corticosterone level. Exposure of the animals to sound stimulus (1 hr or 2 hr) produced a marked decrease in gastric secretion and a concomitant increase in plasma corticosterone. It appears that in producing these effects sound stimulus acted as a stressor. Furthermore, a paradoxical increase in secretion was noted in the first hour collection prior to the sound stimulus. This initial increase in secretion may be due to an adaptive compensatory mechanism in anticipation of its marked inhibition.", "contents": "Effects of sound stimulus on gastric secretion and plasma corticosterone level in rats. The effects of sound stimulus were studied on the gastric secretion in rats with chronically implanted cannulas. Attempts were made to correlate the changes in the secretion with those of the plasma corticosterone level. Exposure of the animals to sound stimulus (1 hr or 2 hr) produced a marked decrease in gastric secretion and a concomitant increase in plasma corticosterone. It appears that in producing these effects sound stimulus acted as a stressor. Furthermore, a paradoxical increase in secretion was noted in the first hour collection prior to the sound stimulus. This initial increase in secretion may be due to an adaptive compensatory mechanism in anticipation of its marked inhibition."} {"id": "PMID:1257615", "title": "Effects of subtoxic lead levels on pregnant women in the state of Missouri.", "content": "Cords, placentas, placental membranes, and maternal and fetal blood were collected from 249 women delivered in Columbia, Missouri (Region I). The same samples were obtained from 253 women delivered in Rolla, Missouri (Region II), near lead mining areas. The incidence of term pregnancies with early membrane rupture was 0.41% in Region I and 17% in Region II. The incidence of premature deliveries was 3% and 13.04% respectively. Lead concentration in blood and placental tissues of term pregnancies revealed no significant changes. In term with early membrane rupture, blood concentration of lead was higher, as was the case in placental tissues and cord. Lead concentration was highest in membrane tissues, in mug/100 grams (Regions I and II respectively): placenta, 6.0 +/- 0.01 and 7.0 +/- 0.03; cord, 11.0 +/- 0.34 and 12.0 +/- 0.18; membrane, 38.9 +/- 2.64 and 45.3 +/- 3.12. A high positive correlation (r = 0.2941) between lead concentration in maternal and fetal blood existed. Both were significantly (P less than 0.01) higher in preterm pregnancies and early membrane ruptures than in term pregnancies. These data suggest that subtoxic levels of lead could increase the incidence of early membrane rupture and premature deliveries.", "contents": "Effects of subtoxic lead levels on pregnant women in the state of Missouri. Cords, placentas, placental membranes, and maternal and fetal blood were collected from 249 women delivered in Columbia, Missouri (Region I). The same samples were obtained from 253 women delivered in Rolla, Missouri (Region II), near lead mining areas. The incidence of term pregnancies with early membrane rupture was 0.41% in Region I and 17% in Region II. The incidence of premature deliveries was 3% and 13.04% respectively. Lead concentration in blood and placental tissues of term pregnancies revealed no significant changes. In term with early membrane rupture, blood concentration of lead was higher, as was the case in placental tissues and cord. Lead concentration was highest in membrane tissues, in mug/100 grams (Regions I and II respectively): placenta, 6.0 +/- 0.01 and 7.0 +/- 0.03; cord, 11.0 +/- 0.34 and 12.0 +/- 0.18; membrane, 38.9 +/- 2.64 and 45.3 +/- 3.12. A high positive correlation (r = 0.2941) between lead concentration in maternal and fetal blood existed. Both were significantly (P less than 0.01) higher in preterm pregnancies and early membrane ruptures than in term pregnancies. These data suggest that subtoxic levels of lead could increase the incidence of early membrane rupture and premature deliveries."} {"id": "PMID:1257616", "title": "Models for clinical disease. I. Biochemical cardiotoxicity of a coenzyme Q10-inhibitor in rats.", "content": "The pharmacology and toxicity in animals of synthetic analogs of essential metabolites, which show in vitro antagonism of the metabolite, may point out pathology associated with a deficiency of the metabolite. On this basis, 2-hydroxy-3-n-dodecylmercapto-1,4-naphthoquinone, a potent in vitro inhibitor of a mitochondrial coenzyme Q10-enzyme, was administered to rats. The specific activities and the percent deficiencies of the succinate dehydrogenase-coenzyme Q10 reductase in cardiac mitochondria were significantly increased (0.001 less than P less than 0.01). These enzyme activities were unchanged in leucocytes and in the dorsal aorta. This biochemical cardiotoxicity of an antimetabolite of coenzyme Q10 adds to the advancing knowledge on coenzyme Q10 in cardiac metabolism and disease, and could correlate with the cardiotoxicity of the clinical antitumor drug, adriamycin.", "contents": "Models for clinical disease. I. Biochemical cardiotoxicity of a coenzyme Q10-inhibitor in rats. The pharmacology and toxicity in animals of synthetic analogs of essential metabolites, which show in vitro antagonism of the metabolite, may point out pathology associated with a deficiency of the metabolite. On this basis, 2-hydroxy-3-n-dodecylmercapto-1,4-naphthoquinone, a potent in vitro inhibitor of a mitochondrial coenzyme Q10-enzyme, was administered to rats. The specific activities and the percent deficiencies of the succinate dehydrogenase-coenzyme Q10 reductase in cardiac mitochondria were significantly increased (0.001 less than P less than 0.01). These enzyme activities were unchanged in leucocytes and in the dorsal aorta. This biochemical cardiotoxicity of an antimetabolite of coenzyme Q10 adds to the advancing knowledge on coenzyme Q10 in cardiac metabolism and disease, and could correlate with the cardiotoxicity of the clinical antitumor drug, adriamycin."} {"id": "PMID:1257617", "title": "Evidence for a dopamine sensitive receptor in the young rat aorta.", "content": "Dopamine caused relaxation in young rat but not old rat aortae contracted with prostaglandin F2 alpha. The antagonizing action of propranolol was less effective on the relaxing effect of dopamine than that of isoproterenol or norepinephrine. Chlorpromazine or haloperidol abolished the relaxing effect of dopamine but only reduced the effect of norepinephrine and isoproterenol. The relaxing effect of dopamine is mainly mediated by the activation of dopamine sensitive receptors.", "contents": "Evidence for a dopamine sensitive receptor in the young rat aorta. Dopamine caused relaxation in young rat but not old rat aortae contracted with prostaglandin F2 alpha. The antagonizing action of propranolol was less effective on the relaxing effect of dopamine than that of isoproterenol or norepinephrine. Chlorpromazine or haloperidol abolished the relaxing effect of dopamine but only reduced the effect of norepinephrine and isoproterenol. The relaxing effect of dopamine is mainly mediated by the activation of dopamine sensitive receptors."} {"id": "PMID:1257618", "title": "A comparison between the haemagglutination inhibition and complement fixation tests for Newcastle disease.", "content": "The value of the complement fixation (CF) test as a means of assessing the immune response of fowls to Newcastle disease virus was examined using several strains of virus. A close degree of correlation was found between the CF test and the simpler haemagglutination-inhibition (HI) test. Like the HI test, the CF test only gave an indication of the immune status and was not a direct measurement of immunity.", "contents": "A comparison between the haemagglutination inhibition and complement fixation tests for Newcastle disease. The value of the complement fixation (CF) test as a means of assessing the immune response of fowls to Newcastle disease virus was examined using several strains of virus. A close degree of correlation was found between the CF test and the simpler haemagglutination-inhibition (HI) test. Like the HI test, the CF test only gave an indication of the immune status and was not a direct measurement of immunity."} {"id": "PMID:1257619", "title": "The inactivity of diamphenethide against liver fluke in certain species of mammals.", "content": "Diamphenethide is inactive against Fasciola hepatica in the rat, although the free amine is active. Extracts of rat liver failed to deacetylate diamphenethide to give the free amine. Diamphenethide is active against fluke in the sheep, less effective in the cow and mouse and not active in the rabbit, even though liver extracts of all four species are capable of liberating the free amine.", "contents": "The inactivity of diamphenethide against liver fluke in certain species of mammals. Diamphenethide is inactive against Fasciola hepatica in the rat, although the free amine is active. Extracts of rat liver failed to deacetylate diamphenethide to give the free amine. Diamphenethide is active against fluke in the sheep, less effective in the cow and mouse and not active in the rabbit, even though liver extracts of all four species are capable of liberating the free amine."} {"id": "PMID:1257620", "title": "The fasciolicidal activity of 4, 4'-diaminodiphenylsulphide.", "content": "4, 4'-diaminodiphenylsulphide is an effective fasciolicide against three-week-old Fasciola hepatica in the sheep at 50 mg/kg per os. The di-N-acetyl derivative is also an effective fasciolicide and is less toxic.", "contents": "The fasciolicidal activity of 4, 4'-diaminodiphenylsulphide. 4, 4'-diaminodiphenylsulphide is an effective fasciolicide against three-week-old Fasciola hepatica in the sheep at 50 mg/kg per os. The di-N-acetyl derivative is also an effective fasciolicide and is less toxic."} {"id": "PMID:1257621", "title": "A rotavirus in lambs with diarrhoea.", "content": "A reovirus-like agent was identified from an outbreak of enteritis in young lambs. From its morphology and immunological relationship with calf rotavirus, it was concluded that it was a rotavirus which infects lambs.", "contents": "A rotavirus in lambs with diarrhoea. A reovirus-like agent was identified from an outbreak of enteritis in young lambs. From its morphology and immunological relationship with calf rotavirus, it was concluded that it was a rotavirus which infects lambs."} {"id": "PMID:1257622", "title": "The efficacy of thiabendazole against the arrested larvae of some Trichostrongylidae and Chabertia ovina in sheep.", "content": "The activity of thiabendazole at 100 mg/kg was tested against the arrested larvae of Ostertagia spp, Haemonchus contortus, Trichostrongylus axei, Nematodirus spp and Chabertia ovina in natural infections, in 10-month-old lambs. The result, assessed by means of worm counts, showed the treatment to be very effective.", "contents": "The efficacy of thiabendazole against the arrested larvae of some Trichostrongylidae and Chabertia ovina in sheep. The activity of thiabendazole at 100 mg/kg was tested against the arrested larvae of Ostertagia spp, Haemonchus contortus, Trichostrongylus axei, Nematodirus spp and Chabertia ovina in natural infections, in 10-month-old lambs. The result, assessed by means of worm counts, showed the treatment to be very effective."} {"id": "PMID:1257623", "title": "Experimental respiratory disease in dogs due to Bordetella bronchiseptica.", "content": "Young dogs of two age groups, six weeks and 12 weeks respectively, were infected by aerosol with a strain of Bordetella bronchiseptica which had been isolated from a dog with pneumonia. Clinical respiratory disease characterised by coughing and in some cases purulent nasal discharge was induced in both groups of infected dogs and also in dogs kept in contact. B bronchiseptica was recovered from the nasal cavity, trachea, bronchi and lung parenchyma of infected and contact animals. At necropsy, masses of Gram-negative bacteria were found trapped in the cilia of the respiratory epithelia and there was an exudate containing neutrophils in the mucosae of the respiratory tract at all levels. A close similarity was noted between the lesions produced in the dog and those described in pertussis infection in man. Experimental respiratory disease in the dog due to B bronchiseptica may offer a model system for the study of the human disease.", "contents": "Experimental respiratory disease in dogs due to Bordetella bronchiseptica. Young dogs of two age groups, six weeks and 12 weeks respectively, were infected by aerosol with a strain of Bordetella bronchiseptica which had been isolated from a dog with pneumonia. Clinical respiratory disease characterised by coughing and in some cases purulent nasal discharge was induced in both groups of infected dogs and also in dogs kept in contact. B bronchiseptica was recovered from the nasal cavity, trachea, bronchi and lung parenchyma of infected and contact animals. At necropsy, masses of Gram-negative bacteria were found trapped in the cilia of the respiratory epithelia and there was an exudate containing neutrophils in the mucosae of the respiratory tract at all levels. A close similarity was noted between the lesions produced in the dog and those described in pertussis infection in man. Experimental respiratory disease in the dog due to B bronchiseptica may offer a model system for the study of the human disease."} {"id": "PMID:1257624", "title": "Comparison of the pharmacokinetics of penicillin G and ampicillin in the horse.", "content": "The affinity and the binding capacity of horse serum proteins for ampicillin and penicillin G were measured by equilibrium dialysis or ultrafiltration technique. From the figures thus obtained it may be concluded that in the range of therapeutic concentrations the protein-bound fraction accounts for 6 X 8-8 per cent of the total ampicillin concentration and for 52-54 per cent of the total penicillin G concentration in serum. The rate of elimination of ampicillin and penicillin G in horses was assessed by following serum concentrations after a single intravenous injection. The biological half life of ampicillin was found to be 93 min and that of penicillin G 53 min in adult horses with unimpaired circulation and intact kidney and liver function.", "contents": "Comparison of the pharmacokinetics of penicillin G and ampicillin in the horse. The affinity and the binding capacity of horse serum proteins for ampicillin and penicillin G were measured by equilibrium dialysis or ultrafiltration technique. From the figures thus obtained it may be concluded that in the range of therapeutic concentrations the protein-bound fraction accounts for 6 X 8-8 per cent of the total ampicillin concentration and for 52-54 per cent of the total penicillin G concentration in serum. The rate of elimination of ampicillin and penicillin G in horses was assessed by following serum concentrations after a single intravenous injection. The biological half life of ampicillin was found to be 93 min and that of penicillin G 53 min in adult horses with unimpaired circulation and intact kidney and liver function."} {"id": "PMID:1257625", "title": "Inhibition of the bactericidal activity of bovine polymorphonuclear leucocytes and related systems by casein.", "content": "Polymorphonuclear leucocytes (PMN) obtained from lactating cows' udders were deficient in their ability to kill Staphylococcus aureus compared with PMN isolated from blood. However, blood PMN suspended in separated milk or in the presence of casein were similarly impaired. Casein was found to inhibit in vitro the bactericidal activities of histone, the lactoperoxidase-H2O2-KI system and PMN lysates. Electron microscopy showed that casein was ingested by PMN with the formation of phagocytic vacuoles. These observations provide the basis of a hypothesis explaining the bactericidal deficiency of milk PMN and the consequent susceptibility of the udder to infection.", "contents": "Inhibition of the bactericidal activity of bovine polymorphonuclear leucocytes and related systems by casein. Polymorphonuclear leucocytes (PMN) obtained from lactating cows' udders were deficient in their ability to kill Staphylococcus aureus compared with PMN isolated from blood. However, blood PMN suspended in separated milk or in the presence of casein were similarly impaired. Casein was found to inhibit in vitro the bactericidal activities of histone, the lactoperoxidase-H2O2-KI system and PMN lysates. Electron microscopy showed that casein was ingested by PMN with the formation of phagocytic vacuoles. These observations provide the basis of a hypothesis explaining the bactericidal deficiency of milk PMN and the consequent susceptibility of the udder to infection."} {"id": "PMID:1257626", "title": "A cinefluoroscopic study of the caecal base of the horse.", "content": "Separate mechanisms exist for transporting ingesta and gas from the caecum to the colon. Both involve the isolation of the cranial part of the base by a constriction cranial to the ileal papilla. This involves elevation of the floor of the base and is associated with dilation of the caecocolic ostium which at other times is closed. Contraction of the ingesta-filled cranial compartment expels some material to the colon but allows most to return to the body. Contractions which discharge gas do not result in the passage of significant amounts of ingesta. The gas expelled is at once hurried through much of the ascending colon. Any considerable reflux to the caecum is prevented by the sigmoid configuration of the caecocolic junction.", "contents": "A cinefluoroscopic study of the caecal base of the horse. Separate mechanisms exist for transporting ingesta and gas from the caecum to the colon. Both involve the isolation of the cranial part of the base by a constriction cranial to the ileal papilla. This involves elevation of the floor of the base and is associated with dilation of the caecocolic ostium which at other times is closed. Contraction of the ingesta-filled cranial compartment expels some material to the colon but allows most to return to the body. Contractions which discharge gas do not result in the passage of significant amounts of ingesta. The gas expelled is at once hurried through much of the ascending colon. Any considerable reflux to the caecum is prevented by the sigmoid configuration of the caecocolic junction."} {"id": "PMID:1257627", "title": "The relationship between Trichuris trichiura (Linnaeus 1758) of man and Trichuris suis (Schrank 1788) of the pig.", "content": "Studies were made on the relationship between Trichuris suis of the pig and T trichiura of man. Comparative morphological and developmental studies revealed differences in sizes of the eggs and infective first stage larvae, in the rate of development to the infective larval stage and in development within young pigs following experimental infection. Successful cross infections of man with T suis ova and of pigs with T trichiura ova were achieved for the first time. T suis eggs recovered from one human experimental infection were used to produce a patent infection in a pig. It is argued that while the successful cross infections suggest a close evolutionary link, the differences in morphology, exogenous and endogenous development provide sufficient criteria for the two parasites to be maintained as separate species.", "contents": "The relationship between Trichuris trichiura (Linnaeus 1758) of man and Trichuris suis (Schrank 1788) of the pig. Studies were made on the relationship between Trichuris suis of the pig and T trichiura of man. Comparative morphological and developmental studies revealed differences in sizes of the eggs and infective first stage larvae, in the rate of development to the infective larval stage and in development within young pigs following experimental infection. Successful cross infections of man with T suis ova and of pigs with T trichiura ova were achieved for the first time. T suis eggs recovered from one human experimental infection were used to produce a patent infection in a pig. It is argued that while the successful cross infections suggest a close evolutionary link, the differences in morphology, exogenous and endogenous development provide sufficient criteria for the two parasites to be maintained as separate species."} {"id": "PMID:1257628", "title": "Tissue damage and concentration at the injection site after intramuscular injection of chemotherapeutics and vehicles in pigs.", "content": "Intramuscular injection sites were examined for macroscopical and microscopical changes and for residues of drugs six and 30 days after injection of chemotherapeutic preparations or vehicles in swine. The chemotherapeutic preparations contained sulphonamide and/or trimethoprim. All the chemotherapeutic preparations and the vehicles except physiological saline and sterile water caused macroscopical and microscopical changes, mainly appearing as areas of necrotic muscle tissue six days after the injection and as scar tissue 30 days after the injection. Residues of drugs were found at nearly all the injection sites six days after the injection, while 30 days after the injection only residues of sulphonamides were detectable in nearly half of the injection sites.", "contents": "Tissue damage and concentration at the injection site after intramuscular injection of chemotherapeutics and vehicles in pigs. Intramuscular injection sites were examined for macroscopical and microscopical changes and for residues of drugs six and 30 days after injection of chemotherapeutic preparations or vehicles in swine. The chemotherapeutic preparations contained sulphonamide and/or trimethoprim. All the chemotherapeutic preparations and the vehicles except physiological saline and sterile water caused macroscopical and microscopical changes, mainly appearing as areas of necrotic muscle tissue six days after the injection and as scar tissue 30 days after the injection. Residues of drugs were found at nearly all the injection sites six days after the injection, while 30 days after the injection only residues of sulphonamides were detectable in nearly half of the injection sites."} {"id": "PMID:1257629", "title": "Some consequences of the ingestion by young and growing pigs of feed contaminated with ergot.", "content": "Growing pigs were fed freshly milled ergot sclerotia (Claviceps purpurea Fr (Tul)) from North American wheat containing 0-31 per cent of total alkaloids of which 30 per cent was ergotoxine, 30 per cent ergosine, 20 per cent ergotamine and 20 per cent other ergot alkaloids. Pigs were induced to ingest a diet heavily contaminated with ergot (10 per cent w/w). The presence of ergot reduced feed intake and growth of the pigs, but there was no evidence of peripheral necrosis, of internal or external haemorrhage, or of changes in haemotological characteristics. Balance experiments in which the diet was contaminated with 4 per cent (w/w) of ergot showed that 90 per cent of the alkaloids were absorbed by the pigs, but none could be detected in tissues or urine. The ingestion of ergot did not affect the digestibility of the diet, but the urinary excretion of nitrogen was increased and the retention of nitrogen reduced. The presence of ricinoleic acid was shown to be a useful diagnostic feature of ergot contamination of diets, digesta and faeces; it was not found in body tissues.", "contents": "Some consequences of the ingestion by young and growing pigs of feed contaminated with ergot. Growing pigs were fed freshly milled ergot sclerotia (Claviceps purpurea Fr (Tul)) from North American wheat containing 0-31 per cent of total alkaloids of which 30 per cent was ergotoxine, 30 per cent ergosine, 20 per cent ergotamine and 20 per cent other ergot alkaloids. Pigs were induced to ingest a diet heavily contaminated with ergot (10 per cent w/w). The presence of ergot reduced feed intake and growth of the pigs, but there was no evidence of peripheral necrosis, of internal or external haemorrhage, or of changes in haemotological characteristics. Balance experiments in which the diet was contaminated with 4 per cent (w/w) of ergot showed that 90 per cent of the alkaloids were absorbed by the pigs, but none could be detected in tissues or urine. The ingestion of ergot did not affect the digestibility of the diet, but the urinary excretion of nitrogen was increased and the retention of nitrogen reduced. The presence of ricinoleic acid was shown to be a useful diagnostic feature of ergot contamination of diets, digesta and faeces; it was not found in body tissues."} {"id": "PMID:1257630", "title": "Observations on the alimentary tract of gnotobiotic lambs.", "content": "Seventeen gnotobiotic lambs were reared up to 21 weeks of age on cows' milk followed by sterile solid diets similar to diets fed to conventional lambs. Seven were inoculated with limited defined populations of rumen bacteria, seven were left uninoculated and three were dosed with rumen contents from conventional sheep ('conventionalised'). Seven naturally-born lambs were reared for purposes of comparison. As with other species of gnotobiotic animals, both the inoculated and the uninoculated gnotobiotic lambs had small, poorly developed lymph nodes, soft colon contents and thin intestinal walls. Unlike other species the caeca of gnotobiotic lambs were of normal size. The overall size of the reticulo-rumen including contents relative to body weight was similar in gnotobiotic and conventional lambs. However, macroscopically, the musculature of the rumen seemed to be poorly developed and histological studies showed hypoplasia of the muscle tissue of both the rumen and reticulum. Rumination was noted only infrequently in gnotobiotic lambs. The epithelium of the rumen and reticulum of the uninoculated gnotobiotic lambs was similar to that of neonatal lambs, but there was normal development of papillae in gnotobiotic lambs inoculated with limited defined populations of rumen bacteria and in conventionalised lambs. Degenerative changes were observed histologically in some of the organs of gnotobiotic lambs which were consistent with nutritional deficiencies.", "contents": "Observations on the alimentary tract of gnotobiotic lambs. Seventeen gnotobiotic lambs were reared up to 21 weeks of age on cows' milk followed by sterile solid diets similar to diets fed to conventional lambs. Seven were inoculated with limited defined populations of rumen bacteria, seven were left uninoculated and three were dosed with rumen contents from conventional sheep ('conventionalised'). Seven naturally-born lambs were reared for purposes of comparison. As with other species of gnotobiotic animals, both the inoculated and the uninoculated gnotobiotic lambs had small, poorly developed lymph nodes, soft colon contents and thin intestinal walls. Unlike other species the caeca of gnotobiotic lambs were of normal size. The overall size of the reticulo-rumen including contents relative to body weight was similar in gnotobiotic and conventional lambs. However, macroscopically, the musculature of the rumen seemed to be poorly developed and histological studies showed hypoplasia of the muscle tissue of both the rumen and reticulum. Rumination was noted only infrequently in gnotobiotic lambs. The epithelium of the rumen and reticulum of the uninoculated gnotobiotic lambs was similar to that of neonatal lambs, but there was normal development of papillae in gnotobiotic lambs inoculated with limited defined populations of rumen bacteria and in conventionalised lambs. Degenerative changes were observed histologically in some of the organs of gnotobiotic lambs which were consistent with nutritional deficiencies."} {"id": "PMID:1257631", "title": "Isolation of a protective, non-toxic capsular antigen from Pasteurella multocida, types B and E.", "content": "Separation of the capsular antigen and endotoxin from saline extracts of Pasteurella multocida type B was achieved by fractional precipitation from aqueous solution by addition of polar organic solvents. Biological tests for the presence of endotoxin showed that it was absent from capsular antigen preparations so obtained. Properties of the capsular antigen suggested that it was a high molecular weight acidic polysaccharide. The solvent fractionation method was found to be equally applicable to separation of capsular antigen and endotoxin of P multocida type E. The type B capsular antigen in the presence of aluminium hydroxide gel adjuvant, was poorly immunogenic in rabbits. In cattle, however, a dose-dependent serological response was obtained as demonstrated by the mouse passive protection test.", "contents": "Isolation of a protective, non-toxic capsular antigen from Pasteurella multocida, types B and E. Separation of the capsular antigen and endotoxin from saline extracts of Pasteurella multocida type B was achieved by fractional precipitation from aqueous solution by addition of polar organic solvents. Biological tests for the presence of endotoxin showed that it was absent from capsular antigen preparations so obtained. Properties of the capsular antigen suggested that it was a high molecular weight acidic polysaccharide. The solvent fractionation method was found to be equally applicable to separation of capsular antigen and endotoxin of P multocida type E. The type B capsular antigen in the presence of aluminium hydroxide gel adjuvant, was poorly immunogenic in rabbits. In cattle, however, a dose-dependent serological response was obtained as demonstrated by the mouse passive protection test."} {"id": "PMID:1257632", "title": "Osmotic and oxidative haemolysis of erythrocytes in calves with white muscle disease.", "content": "The stability of erythrocytes to both osmotic and oxidative haemolysis was studied in naturally occuring cases of white muscle disease of calves two to 14 weeks old. During clinical and subclinical disease the incidence of haemolysis when erythrocytes were exposed to 0-588 per cent NaCl was 74-3 +/-18-8 per cent and 76-6+/-18-6 per cent respectively, whereas in clinically healthy animals receiving 30 mg vitamin E per kg feedstuff the incidence of haemolysis was only 55-9+/-12-7 per cent. Erythrocytes of the calves receiving vitamin E supplements were completely resistent to peroxidative haemolysis whereas in the clinical and preclinical cases approximately 12-5 per cent of cells were lysed.", "contents": "Osmotic and oxidative haemolysis of erythrocytes in calves with white muscle disease. The stability of erythrocytes to both osmotic and oxidative haemolysis was studied in naturally occuring cases of white muscle disease of calves two to 14 weeks old. During clinical and subclinical disease the incidence of haemolysis when erythrocytes were exposed to 0-588 per cent NaCl was 74-3 +/-18-8 per cent and 76-6+/-18-6 per cent respectively, whereas in clinically healthy animals receiving 30 mg vitamin E per kg feedstuff the incidence of haemolysis was only 55-9+/-12-7 per cent. Erythrocytes of the calves receiving vitamin E supplements were completely resistent to peroxidative haemolysis whereas in the clinical and preclinical cases approximately 12-5 per cent of cells were lysed."} {"id": "PMID:1257633", "title": "Production of large quantities of interferon with calf testicular cells and leucocytes.", "content": "Interferon (IF) was induced in calf testicle monolayer cultures and leucocycte suspension cultures with Semliki forest virus and Newcastle disease virus to evaluate the potency of those cells for producing IF in large quantities for clinical experiments. Interferon activity was measured by an RNA-inhibition test using Semliki forest virus as challenge. To produce 10(6) units of IF, leucocytes from 67-5 litres of blood or 7-2 X 10(9) testicle cells were needed.", "contents": "Production of large quantities of interferon with calf testicular cells and leucocytes. Interferon (IF) was induced in calf testicle monolayer cultures and leucocycte suspension cultures with Semliki forest virus and Newcastle disease virus to evaluate the potency of those cells for producing IF in large quantities for clinical experiments. Interferon activity was measured by an RNA-inhibition test using Semliki forest virus as challenge. To produce 10(6) units of IF, leucocytes from 67-5 litres of blood or 7-2 X 10(9) testicle cells were needed."} {"id": "PMID:1257681", "title": "[Condylar osteonecrosis of the knee in adults and aged. Study of 36 cases].", "content": "The authors analyse the clinical symptoms, the etiology, and the evolution of condylar osteonecrosis of the knee with reference to 36 personal cases, including 28 unilateral forms and 8 bilateral forms. They confirm the predominance of the condition in women and the fact that it usually commences after the age of 50 years. They followed the evolution of the condition in 27 patients, in 20 of them for from 3 to 12 years. Evolution was good or excellent in 12 patients. The authors showed that the existence of a healthy lateral segment on the affected condyle is one element that indicates a good prognosis; they found that intra-articular injections of corticoids did not affect the evolution unfavourably, but that the coexistence of several other associated pathological conditions (vasxular, metabolic...) indicated a poor prognosis. If the precipitating cause of the condylar osteonecrosis of the knee is not known, with the exception of some cases commencing after trauma, the authors put forward the hypothesis of chronic condylar circulatory insufficiency or stasis as the cause leading to the condition, the latter occurring in cases when an already delicate vascular equilibrium is upset.", "contents": "[Condylar osteonecrosis of the knee in adults and aged. Study of 36 cases]. The authors analyse the clinical symptoms, the etiology, and the evolution of condylar osteonecrosis of the knee with reference to 36 personal cases, including 28 unilateral forms and 8 bilateral forms. They confirm the predominance of the condition in women and the fact that it usually commences after the age of 50 years. They followed the evolution of the condition in 27 patients, in 20 of them for from 3 to 12 years. Evolution was good or excellent in 12 patients. The authors showed that the existence of a healthy lateral segment on the affected condyle is one element that indicates a good prognosis; they found that intra-articular injections of corticoids did not affect the evolution unfavourably, but that the coexistence of several other associated pathological conditions (vasxular, metabolic...) indicated a poor prognosis. If the precipitating cause of the condylar osteonecrosis of the knee is not known, with the exception of some cases commencing after trauma, the authors put forward the hypothesis of chronic condylar circulatory insufficiency or stasis as the cause leading to the condition, the latter occurring in cases when an already delicate vascular equilibrium is upset."} {"id": "PMID:1257682", "title": "[Osteonecrosis of the femoral condyles in adults. Apropos of 30 personal cases].", "content": "On the basis of a series of 30 personal cases, the authors describe the circumstances in which osteonecrosis of the femoral condyles occurs, the clinical and radiological characteristics, the evolution of the disease, and some of the associated therapeutic problems. They emphasize particularly the difference between the primary forms, which are the prerogative of women over 50 years of age and are of a limited character, and the secondary forms that are essentially linked to prolonged corticotherapy. The secondary forms are found in persons of both sexes between the ages of 20 and 40 years and consist of diffuse lesions (frequent extensive epiphyseal reorganization, bilaterality, and associations with other sites). As the evolution of the disorder under simple medical treatment is usually fairly favourable, the authors consider that indications for surgery should be restricted to the infrequent forms (10 to 15% of cases) that progress rapidly towards arthrosis.", "contents": "[Osteonecrosis of the femoral condyles in adults. Apropos of 30 personal cases]. On the basis of a series of 30 personal cases, the authors describe the circumstances in which osteonecrosis of the femoral condyles occurs, the clinical and radiological characteristics, the evolution of the disease, and some of the associated therapeutic problems. They emphasize particularly the difference between the primary forms, which are the prerogative of women over 50 years of age and are of a limited character, and the secondary forms that are essentially linked to prolonged corticotherapy. The secondary forms are found in persons of both sexes between the ages of 20 and 40 years and consist of diffuse lesions (frequent extensive epiphyseal reorganization, bilaterality, and associations with other sites). As the evolution of the disorder under simple medical treatment is usually fairly favourable, the authors consider that indications for surgery should be restricted to the infrequent forms (10 to 15% of cases) that progress rapidly towards arthrosis."} {"id": "PMID:1257683", "title": "[Indications and possibilities of total prosthesis of the hip].", "content": "If all the non-traumatic coxopathies are considered, it can be said that there is practically no limit to the possibilities of operations for total prostheses fo the hip. In particular, all the technical problems posed by certain forms of coxopathy can be solved. Only grave deterioration in the general condition of the patient and non-tubercular infections constitute contra-indications. This is, of course, not new and is valid for all orthopaedic surgery. Only the future will show if this concept is true.", "contents": "[Indications and possibilities of total prosthesis of the hip]. If all the non-traumatic coxopathies are considered, it can be said that there is practically no limit to the possibilities of operations for total prostheses fo the hip. In particular, all the technical problems posed by certain forms of coxopathy can be solved. Only grave deterioration in the general condition of the patient and non-tubercular infections constitute contra-indications. This is, of course, not new and is valid for all orthopaedic surgery. Only the future will show if this concept is true."} {"id": "PMID:1257684", "title": "[Foot involvement in Paget's disease of bone].", "content": "Paget's disease of the bones of the feet is not unusual. Twenty patients out of every hundred present the signs of Paget's disease in the foot bones. The calcaneus is the bone most often affected (18 cases) but the cuboid, the metatarsals, and the astragalus (often as well as the calcaneus) may also be affected. Paget's disease of the foot remains latent clinically: 2 patients complained of talalgia; a third had a deformation of the rear part of the foot which made it difficult to wear a shoe. Pagetic deformations of the lower limb affect the foot but without pain. They are often compensated for by putting more weight on the fore-foot in cases of shortening of the lower limb or on the external arch in cases of bowed deformation of the lower limb.", "contents": "[Foot involvement in Paget's disease of bone]. Paget's disease of the bones of the feet is not unusual. Twenty patients out of every hundred present the signs of Paget's disease in the foot bones. The calcaneus is the bone most often affected (18 cases) but the cuboid, the metatarsals, and the astragalus (often as well as the calcaneus) may also be affected. Paget's disease of the foot remains latent clinically: 2 patients complained of talalgia; a third had a deformation of the rear part of the foot which made it difficult to wear a shoe. Pagetic deformations of the lower limb affect the foot but without pain. They are often compensated for by putting more weight on the fore-foot in cases of shortening of the lower limb or on the external arch in cases of bowed deformation of the lower limb."} {"id": "PMID:1257685", "title": "[Contribution of scanning electron microscopy to the study of normal and pathological human synovial membrane].", "content": "Scanning electron microscopy permits three-dimensional morphological study of the outer layer of the synovial membrane. This article concerns the study of 15 surgical samples of normal and pathological human synovial membranes: 3 normal synovial membranes, 6 inflammatory synovial membranes, 5 arthrosic synovial membranes, 1 tuberculous tenosynovitis. The samples were washed, fixed in a mixture of glutaraldehyde and iso-osmotic paraformaldehyde, dehydrated in increasing concentrations of alcohol and at the critical point, and then subjected to double metallization (aluminium and gold). Certain portions were treated with hyaluronidase. Hypertrophy of the villi, considerable in inflammatory synovial membranes, minimal in arthrosic synovial membranes, and absent in the normal synovial membrane, was confirmed. The outer layer is composed of cells of different sizes with spaces betwen, in which images indicating intercellular bridges can just be seen. The surface of the cells is irregular and covered with numerous microvilli. The arthrosic synovial membrane is poorly with large cells; in contrast in an inflammatory synovial membrane they are numerous, globular, and project from the surface.", "contents": "[Contribution of scanning electron microscopy to the study of normal and pathological human synovial membrane]. Scanning electron microscopy permits three-dimensional morphological study of the outer layer of the synovial membrane. This article concerns the study of 15 surgical samples of normal and pathological human synovial membranes: 3 normal synovial membranes, 6 inflammatory synovial membranes, 5 arthrosic synovial membranes, 1 tuberculous tenosynovitis. The samples were washed, fixed in a mixture of glutaraldehyde and iso-osmotic paraformaldehyde, dehydrated in increasing concentrations of alcohol and at the critical point, and then subjected to double metallization (aluminium and gold). Certain portions were treated with hyaluronidase. Hypertrophy of the villi, considerable in inflammatory synovial membranes, minimal in arthrosic synovial membranes, and absent in the normal synovial membrane, was confirmed. The outer layer is composed of cells of different sizes with spaces betwen, in which images indicating intercellular bridges can just be seen. The surface of the cells is irregular and covered with numerous microvilli. The arthrosic synovial membrane is poorly with large cells; in contrast in an inflammatory synovial membrane they are numerous, globular, and project from the surface."} {"id": "PMID:1257686", "title": "[Coxarthrosis due to contusion].", "content": "Can a contusion cause coxarthrosis in the absence of both fracture and dislocation? Yes. To demonstrate this the authors report 6 cases that fulfil the following conditions: (1) Simple but violent contusion affecting the greater trochanter or the knee (dashboard accident) or a forced movement, such as in doing the splits; (2) immediate or slightly delayed pain, generally of short duration (a few weeks); (3) absence of coxarthrogenic malformations and absence of pre-existing signs of a pathological hip condition; (4) progressive coxarthrosis on the side of the contusion; (5) chronological relation between the development of the coxarthrosis images and the date of the contusion; (6) subjects less than 35 years of age, in order to eliminate cases with latent primary pre-coxarthrosis. The average age of the six patients at the start of the coxarthrosis was 24.7 years (range: 13 to 33 years); there were four men and two women. In five of the six cases a violent contusion in the trochanter region was involved as a result of a fall on a hard surface or a traffic accident. In one case a forced movement on landing from a jump was involved. Evolution in three periods is usual: the hip is painful either immediately or after a few weeks (particularly on rising after a period in bed for multiple injuries). This post-traumatic pain lasts from ten days to one month, rarely longer. It is followed by a period free of pain that may last from five months to ten years (average: five years). Subsequently there is pain every day and the onset of the limp associated with coxarthrosis. Radiographically the reduction of the joint space and/or the osteophytosis appears after three months to two years (average: one year). However, there may not be any pain associated with these lesions for a long time. The authors propose that the first five conditions enumerated above represent the essential medico-legal conditions of coxarthrosis by contusion. The restriction as regards age (No 6) was introduced only to show clearly the existence of post-contusive coxarthrosis. However, even if one or more of the medico-legal conditions are not fulfilled the imputability may still be valid. Some such cases are discussed.", "contents": "[Coxarthrosis due to contusion]. Can a contusion cause coxarthrosis in the absence of both fracture and dislocation? Yes. To demonstrate this the authors report 6 cases that fulfil the following conditions: (1) Simple but violent contusion affecting the greater trochanter or the knee (dashboard accident) or a forced movement, such as in doing the splits; (2) immediate or slightly delayed pain, generally of short duration (a few weeks); (3) absence of coxarthrogenic malformations and absence of pre-existing signs of a pathological hip condition; (4) progressive coxarthrosis on the side of the contusion; (5) chronological relation between the development of the coxarthrosis images and the date of the contusion; (6) subjects less than 35 years of age, in order to eliminate cases with latent primary pre-coxarthrosis. The average age of the six patients at the start of the coxarthrosis was 24.7 years (range: 13 to 33 years); there were four men and two women. In five of the six cases a violent contusion in the trochanter region was involved as a result of a fall on a hard surface or a traffic accident. In one case a forced movement on landing from a jump was involved. Evolution in three periods is usual: the hip is painful either immediately or after a few weeks (particularly on rising after a period in bed for multiple injuries). This post-traumatic pain lasts from ten days to one month, rarely longer. It is followed by a period free of pain that may last from five months to ten years (average: five years). Subsequently there is pain every day and the onset of the limp associated with coxarthrosis. Radiographically the reduction of the joint space and/or the osteophytosis appears after three months to two years (average: one year). However, there may not be any pain associated with these lesions for a long time. The authors propose that the first five conditions enumerated above represent the essential medico-legal conditions of coxarthrosis by contusion. The restriction as regards age (No 6) was introduced only to show clearly the existence of post-contusive coxarthrosis. However, even if one or more of the medico-legal conditions are not fulfilled the imputability may still be valid. Some such cases are discussed."} {"id": "PMID:1257687", "title": "[Anatomopathology of Paget's disease. Combined approach by conventional methods and ultrastructural study].", "content": "Paget's disease is manifested by bone remodelling where the rate of the resorption-osteogenesis pattern is abnormally enhanced. This leads to the formation of a pathologically structured bone. The bone remodelling does not concern the entire skeletal structure and is unequally active. It is limited by the neighbouring healthy bone in which it can spread out. It can be followed by the development of a sarcoma. When the acetabulum or the femoral head are affected this can occasionally, lead to a coxopathy with cartilage deterioration. An anatomo-pathological study of Paget's disease is necessary for understanding the basis and the limits of biopsy diagnosis as well as its various manifestations (clinical, radiological, biological, scintigraphical, thermographical). This study also serves as a basic for pathogenic discussion.", "contents": "[Anatomopathology of Paget's disease. Combined approach by conventional methods and ultrastructural study]. Paget's disease is manifested by bone remodelling where the rate of the resorption-osteogenesis pattern is abnormally enhanced. This leads to the formation of a pathologically structured bone. The bone remodelling does not concern the entire skeletal structure and is unequally active. It is limited by the neighbouring healthy bone in which it can spread out. It can be followed by the development of a sarcoma. When the acetabulum or the femoral head are affected this can occasionally, lead to a coxopathy with cartilage deterioration. An anatomo-pathological study of Paget's disease is necessary for understanding the basis and the limits of biopsy diagnosis as well as its various manifestations (clinical, radiological, biological, scintigraphical, thermographical). This study also serves as a basic for pathogenic discussion."} {"id": "PMID:1257692", "title": "The effect of amitriptyline on forearm blood flow.", "content": "The local effect of intra-arterial infusion of amitriptyline (AT) on forearm blood flow was studied in seven healthy subjects. AT was infused at rates of 0.05, 0.10, 0.15, and 0.20 mg-min--1 for periods of 5 min. Forearm blood flow showed a dose-dependent increase when the dose exeeded 0.10 mg-min--1. On the highest dose level the blood flow increased on an average by 73%. No systemic effects, as reflected by changes in heart rate, blood pressure, and blood flow in the contralateral forearm, were observed during the infusion. The present data indicate a dilatating effect of AT on resistance vessels possibly mediated by an alpha-adrenergic blockade.", "contents": "The effect of amitriptyline on forearm blood flow. The local effect of intra-arterial infusion of amitriptyline (AT) on forearm blood flow was studied in seven healthy subjects. AT was infused at rates of 0.05, 0.10, 0.15, and 0.20 mg-min--1 for periods of 5 min. Forearm blood flow showed a dose-dependent increase when the dose exeeded 0.10 mg-min--1. On the highest dose level the blood flow increased on an average by 73%. No systemic effects, as reflected by changes in heart rate, blood pressure, and blood flow in the contralateral forearm, were observed during the infusion. The present data indicate a dilatating effect of AT on resistance vessels possibly mediated by an alpha-adrenergic blockade."} {"id": "PMID:1257693", "title": "Unimpeded plasma renin increase after intravenous furosemide during saline replacement.", "content": "The effect on plasma renin activity of intravenous furosemide combined with saline replacement of the volume depletion was studied in twelve patients with insignificant heart disease. In ten of the patients the investigation was repeated without saline replacement. It was found that saline infusion, reducing or eliminating hemoconcentration, had no significant influence on the marked plasma renin increase. In eight of the patients the combined furosemide-saline study was performed during right-hear catheterization. Decrease in atrial pressures, known to occur within 15 min after furosemide intravenously, was virtually absent with the saline replacement. It is concluded that plasma volume reduction after intravenous furosemide is responsible for decreased filling pressures of the ventricles but not for plasma renin increase.", "contents": "Unimpeded plasma renin increase after intravenous furosemide during saline replacement. The effect on plasma renin activity of intravenous furosemide combined with saline replacement of the volume depletion was studied in twelve patients with insignificant heart disease. In ten of the patients the investigation was repeated without saline replacement. It was found that saline infusion, reducing or eliminating hemoconcentration, had no significant influence on the marked plasma renin increase. In eight of the patients the combined furosemide-saline study was performed during right-hear catheterization. Decrease in atrial pressures, known to occur within 15 min after furosemide intravenously, was virtually absent with the saline replacement. It is concluded that plasma volume reduction after intravenous furosemide is responsible for decreased filling pressures of the ventricles but not for plasma renin increase."} {"id": "PMID:1257694", "title": "Selection of routine method for determination of glomerular filtration rate in adult patients.", "content": "The precision and reporducibility of three different clearance methods as used in clinical routine assessment of glomerular filtration rate (GFR) were investigated in 51 patients: total [51Cr]EDTA plasma clearance (E); 24-hr endogenous creatinine clearance (C); and creatinine clearance estimated from the plasma creatinine concentration, weight, and sex- and age-dependent mean creatinine excretion rate (c). The precision and reporducibility (coefficient of variation) for single determinations were, in patients with E greater than 30 ml/min, 5.5 and 4.1% (E); 26.9% (C); and 23.2 and 11.0% (c). The corresponding figures for E less than 30 ml/min were 11.6 and 11.5% (E); 21.9% (C); and 21.4 and 6.5% (c). The precision of C could not be ameliorated by excluding single deviating determinations, but only by excluding patients for whom the precision of 15.5% for mean of three determinations of C (total material) could be reduced to 10% by excluding 25% of the patients. The present data indicate that E in most cases is the method of choice for assessment of GFR in clinical routine work. For changes in renal function, especially at low functional levels, c may be of value.", "contents": "Selection of routine method for determination of glomerular filtration rate in adult patients. The precision and reporducibility of three different clearance methods as used in clinical routine assessment of glomerular filtration rate (GFR) were investigated in 51 patients: total [51Cr]EDTA plasma clearance (E); 24-hr endogenous creatinine clearance (C); and creatinine clearance estimated from the plasma creatinine concentration, weight, and sex- and age-dependent mean creatinine excretion rate (c). The precision and reporducibility (coefficient of variation) for single determinations were, in patients with E greater than 30 ml/min, 5.5 and 4.1% (E); 26.9% (C); and 23.2 and 11.0% (c). The corresponding figures for E less than 30 ml/min were 11.6 and 11.5% (E); 21.9% (C); and 21.4 and 6.5% (c). The precision of C could not be ameliorated by excluding single deviating determinations, but only by excluding patients for whom the precision of 15.5% for mean of three determinations of C (total material) could be reduced to 10% by excluding 25% of the patients. The present data indicate that E in most cases is the method of choice for assessment of GFR in clinical routine work. For changes in renal function, especially at low functional levels, c may be of value."} {"id": "PMID:1257695", "title": "Cardiac effects of amitriptyline in rats.", "content": "The effect of intravenous amitriptyline (0.5-2 mg/kg) on heart rate, blood pressure, ECG, and electrolytes in plasma and heart muscle was studied in rats. In addition, the effect on monophasic action potentials was studied in rats with open chest. Amitriptyline caused a significant decrease in blood pressure and heart rate and a significant prolongation of QRS and PQ duration. At the time of maximal QRS prolongation (mean +94%) the duration of monophasic action potentials was virtually unchanged. Beta-adrenergic blockade by means of pretreatment with 0.1 mg propranolol did not influence the amitriptyline-induced prolongation of QRS duration. Amitriptyline administration causing obvious QRS prolongation induced no detectable changes in plasma and heart muscle electrolytes. The results contradict adrenergic dominance or marked imbalance between intra- and extra-cellular electrolytes as a cause of the ECG changes. The present data indicate that the amitriptyline effect is compatible with a direct quinidine-like action on the heart, resulting mainly in a slowing of impulse propagation in the intracardiac conduction system.", "contents": "Cardiac effects of amitriptyline in rats. The effect of intravenous amitriptyline (0.5-2 mg/kg) on heart rate, blood pressure, ECG, and electrolytes in plasma and heart muscle was studied in rats. In addition, the effect on monophasic action potentials was studied in rats with open chest. Amitriptyline caused a significant decrease in blood pressure and heart rate and a significant prolongation of QRS and PQ duration. At the time of maximal QRS prolongation (mean +94%) the duration of monophasic action potentials was virtually unchanged. Beta-adrenergic blockade by means of pretreatment with 0.1 mg propranolol did not influence the amitriptyline-induced prolongation of QRS duration. Amitriptyline administration causing obvious QRS prolongation induced no detectable changes in plasma and heart muscle electrolytes. The results contradict adrenergic dominance or marked imbalance between intra- and extra-cellular electrolytes as a cause of the ECG changes. The present data indicate that the amitriptyline effect is compatible with a direct quinidine-like action on the heart, resulting mainly in a slowing of impulse propagation in the intracardiac conduction system."} {"id": "PMID:1257696", "title": "Classification of liver diseases by clinical chemical laboratory results and cluster analysis.", "content": "Patients with liver diseases were classified by cluster analysis using only clinical chemical laboratory results. A strong tendency towards correspondence between this classification, based on functional criteria, and the previous diagnoses, based mainly on liver biopsy findings, was found.", "contents": "Classification of liver diseases by clinical chemical laboratory results and cluster analysis. Patients with liver diseases were classified by cluster analysis using only clinical chemical laboratory results. A strong tendency towards correspondence between this classification, based on functional criteria, and the previous diagnoses, based mainly on liver biopsy findings, was found."} {"id": "PMID:1257697", "title": "Production and evaluation of high-quality thyroxine antisera for use in radioimmunoassay.", "content": "High-quality thyroxine (T4) antisera were raised in rabbits. Conjugates of protein and T4 or T4 methyl ester were given intracutaneously in Freund's complete adjuvant at one or two sites on the back at 1/2- to 3-month intervals. Eleven of 16 immunized rabbits produced antiserum with titers higher than 2 commercial antisera and 4 antisera from other laboratories. All 16 antisera had equilibrium constants (K) higher than the 6 reference sera. The highest titer observed was 130,000 with 88 fmol labeled T4 per ml incubate. A drastic increase in K from about 4 X 10(8) to 5.8 X 10(10) 1/mol was observed as the immunization proceeded. Cross-reactivity with triiodothyronine (T3) varied but was generally low. Suppression of the T4 synthesis was attempted by giving 30 nmol (20 mug) T3 per os once a day. Antiserum from rabbits given T3 suppression contained less iodine than antiserum from nonsuppressed control rabbits. The possible reasons for the successful production of the high-quality antisera are discussed.", "contents": "Production and evaluation of high-quality thyroxine antisera for use in radioimmunoassay. High-quality thyroxine (T4) antisera were raised in rabbits. Conjugates of protein and T4 or T4 methyl ester were given intracutaneously in Freund's complete adjuvant at one or two sites on the back at 1/2- to 3-month intervals. Eleven of 16 immunized rabbits produced antiserum with titers higher than 2 commercial antisera and 4 antisera from other laboratories. All 16 antisera had equilibrium constants (K) higher than the 6 reference sera. The highest titer observed was 130,000 with 88 fmol labeled T4 per ml incubate. A drastic increase in K from about 4 X 10(8) to 5.8 X 10(10) 1/mol was observed as the immunization proceeded. Cross-reactivity with triiodothyronine (T3) varied but was generally low. Suppression of the T4 synthesis was attempted by giving 30 nmol (20 mug) T3 per os once a day. Antiserum from rabbits given T3 suppression contained less iodine than antiserum from nonsuppressed control rabbits. The possible reasons for the successful production of the high-quality antisera are discussed."} {"id": "PMID:1257698", "title": "Correlations between the deoxyuridine-suppressed value and some conventional haematological parameters in patients with folate or vitamin B12 deficiency.", "content": "The correlations between the deoxyuridine-suppressed value and some conventional haematological parameters (Hb concentration, red cell count, MCV, total white cell count, red cell folate level and serum vitamin B12 level) have been investigated in 40 patients with megaloblastic haemopoiesis due to folate or vitamin B12. deficiency. The only statistically significant correlations found were (a) an inverse correlation between the deoxyuridine-suppressed value and the Hb level or red cell count in both the folate- and vitamin B12-deficient groups and (b) a direct correlation between the deoxyuridine-suppressed value and MCV in the vitamin B12-deficient group. The results indicated that the deoxyuridine-suppressed value was a better index of the magnitude of the disturbance in red cell production induced by folate or vitamin B12 deficiency than either the red cell folate or serum vitamin B12 levels.", "contents": "Correlations between the deoxyuridine-suppressed value and some conventional haematological parameters in patients with folate or vitamin B12 deficiency. The correlations between the deoxyuridine-suppressed value and some conventional haematological parameters (Hb concentration, red cell count, MCV, total white cell count, red cell folate level and serum vitamin B12 level) have been investigated in 40 patients with megaloblastic haemopoiesis due to folate or vitamin B12. deficiency. The only statistically significant correlations found were (a) an inverse correlation between the deoxyuridine-suppressed value and the Hb level or red cell count in both the folate- and vitamin B12-deficient groups and (b) a direct correlation between the deoxyuridine-suppressed value and MCV in the vitamin B12-deficient group. The results indicated that the deoxyuridine-suppressed value was a better index of the magnitude of the disturbance in red cell production induced by folate or vitamin B12 deficiency than either the red cell folate or serum vitamin B12 levels."} {"id": "PMID:1257699", "title": "Relapsing haemolytic anaemia of pregnancy with negative antiglobulin reaction.", "content": "Four patients are described in whom seven episodes of haemolytic anaemia associated with pregnancy were observed during a follow-up period of 2 to 16 years. Normal haemoglobin levels were found both before and after pregnancy. Despite consistently negative antiglobulin tests, an autoimmune haemolytic mechanism is suggested by the rapid destruction of transfused blood, favourable response to corticosteroids and the development of transient haemolytic anaemia in three of the infants. In view of its unique clinical and laboratory features and relatively mild course, recognition of this condition as a distinct clinical entitity seems to be justified.", "contents": "Relapsing haemolytic anaemia of pregnancy with negative antiglobulin reaction. Four patients are described in whom seven episodes of haemolytic anaemia associated with pregnancy were observed during a follow-up period of 2 to 16 years. Normal haemoglobin levels were found both before and after pregnancy. Despite consistently negative antiglobulin tests, an autoimmune haemolytic mechanism is suggested by the rapid destruction of transfused blood, favourable response to corticosteroids and the development of transient haemolytic anaemia in three of the infants. In view of its unique clinical and laboratory features and relatively mild course, recognition of this condition as a distinct clinical entitity seems to be justified."} {"id": "PMID:1257700", "title": "Streptokinase resistance test in patients with streptococcal infection and/or high antistreptolysin titers.", "content": "The streptokinase resistance test (SRT) has been studied in a group of patients with recent streptococcal infection and/or titres of antistreptolysin higher than 625 units. These patients generally had a higher SRT.", "contents": "Streptokinase resistance test in patients with streptococcal infection and/or high antistreptolysin titers. The streptokinase resistance test (SRT) has been studied in a group of patients with recent streptococcal infection and/or titres of antistreptolysin higher than 625 units. These patients generally had a higher SRT."} {"id": "PMID:1257701", "title": "Haemostatic and lipid abnormalities in hypothyroidism.", "content": "10 patients with hypothyroidism were examined before and 3 months after initiation of thyroxin treatment. All patients had high levels of plasma total cholesterol and total phospholipids, and 5 had an additional hypertriglyceridaemia. 1 patient had a prolonged primary bleeding time and all had a prolonged activated partial thromboplastin time and recalcification time in plasma. Platelet factor 3 activity in platelet rich plasma was reduced and total phospholipid and protein concentration in platelets were low. No significant correlation could be estiblished between the observed lipid, protein and haemostatic parameters, and it is suggested that they represent independent phenomena. All abnormalities were corrected by thyroxin replacement.", "contents": "Haemostatic and lipid abnormalities in hypothyroidism. 10 patients with hypothyroidism were examined before and 3 months after initiation of thyroxin treatment. All patients had high levels of plasma total cholesterol and total phospholipids, and 5 had an additional hypertriglyceridaemia. 1 patient had a prolonged primary bleeding time and all had a prolonged activated partial thromboplastin time and recalcification time in plasma. Platelet factor 3 activity in platelet rich plasma was reduced and total phospholipid and protein concentration in platelets were low. No significant correlation could be estiblished between the observed lipid, protein and haemostatic parameters, and it is suggested that they represent independent phenomena. All abnormalities were corrected by thyroxin replacement."} {"id": "PMID:1257702", "title": "An individual with Hb-Lepore-Baltimore- delta beta-thalassaemia in a Yugoslavian family.", "content": "The clinical, haematological and biochemical findings in a person with delta beta-thalassaemia and Hb-Lepore are described. The patient was a 24-year-old student who suffered from anaemia of intermediate severity with late onset of the clinical manifestations, had minor bone and facial deformities, but had no necessity for regular transfusions. Haemoglobins A and A2 were absent in this individual, and the Hb-Lepore has been identified as Lepore-Baltimore. Heterogeneity of gamma chain of the Hb-F follows the expected pattern. The study provides further evidence that neither beta nor delta chains are synthesized in cis to delta beta-thalassaemia or Hb-Lepore.", "contents": "An individual with Hb-Lepore-Baltimore- delta beta-thalassaemia in a Yugoslavian family. The clinical, haematological and biochemical findings in a person with delta beta-thalassaemia and Hb-Lepore are described. The patient was a 24-year-old student who suffered from anaemia of intermediate severity with late onset of the clinical manifestations, had minor bone and facial deformities, but had no necessity for regular transfusions. Haemoglobins A and A2 were absent in this individual, and the Hb-Lepore has been identified as Lepore-Baltimore. Heterogeneity of gamma chain of the Hb-F follows the expected pattern. The study provides further evidence that neither beta nor delta chains are synthesized in cis to delta beta-thalassaemia or Hb-Lepore."} {"id": "PMID:1257703", "title": "Oxymetholone treatment in aregenerative anaemia. II. Remission and survival--a prospective study.", "content": "This is a prospective multi-center study in which patients with aregenerative anaemia were treated with a standardized high dosage regime of an anabolic steroid (oxymetholone, Anasteron). 53 patients were included and divided into two groups according to bone marrow cellularity. Furthermore the hypocellular group was subdivided in order to make comparison with earlier studies possible. In the hypocellular group, the frequency of remission was 56% and the 2-year-survival from the onset of symptoms was 75%. This is longer than in some earlier studies, perhaps because of possible differences in etiology and/or because of the effect of systematic high dosage, long term androgen therapy. Patient selection was minimized and was not considered to be of major importance. Patients with hypercellular marrows, on the other hand, responded poorly to androgens. In this group 63% died of acute leukaemia, which confirms earlier suggestions that this form of aregenerative anaemia, frequently is of a preleukaemic nature.", "contents": "Oxymetholone treatment in aregenerative anaemia. II. Remission and survival--a prospective study. This is a prospective multi-center study in which patients with aregenerative anaemia were treated with a standardized high dosage regime of an anabolic steroid (oxymetholone, Anasteron). 53 patients were included and divided into two groups according to bone marrow cellularity. Furthermore the hypocellular group was subdivided in order to make comparison with earlier studies possible. In the hypocellular group, the frequency of remission was 56% and the 2-year-survival from the onset of symptoms was 75%. This is longer than in some earlier studies, perhaps because of possible differences in etiology and/or because of the effect of systematic high dosage, long term androgen therapy. Patient selection was minimized and was not considered to be of major importance. Patients with hypercellular marrows, on the other hand, responded poorly to androgens. In this group 63% died of acute leukaemia, which confirms earlier suggestions that this form of aregenerative anaemia, frequently is of a preleukaemic nature."} {"id": "PMID:1257704", "title": "Rheumatoid factor and serum IgG, IgM and IgA levels in rheumatoid arthritis with vasculitis.", "content": "The authors report a significant increase in the rheumatoid factor titre in rheumatoid arthritis patients with vasculitis. A significant rise in IgG and IgA levels was found in uncomplicated RA, when compared with a normal population. The IgM levels were not found to be elevated in this group of RA patients. In the RA patients with vasculitis, on the contrary, the three Ig classes are increased when compared with the normal population, and the IgM level is increased when compared with the uncomplicated RA group. Significant relation was found between log IgM and log R.F. titre in the RA group with vasculitis. It is shown that the mild reduction of serum (by dithiothreitol 0.004 M) causes a complete negativity of the R. F. in all cases. It is concluded that the haemagglutination and the latex precipitation in vitro are induced by IgM-R. F. and not by IgG and IgA-R. F. molecules. Only free sites of IgM-R.F. play a functional role in the determination of the R. F. -titre. The authors postulated that increase in IgM in RA patients with vasculitis is partially due to the presence of free IgM-R. F. molecules in serum. Finally it is concluded that hidden IgM-R. F. molecules in patients with lower R. F. titre are not quantified by immunodiffusion methods.", "contents": "Rheumatoid factor and serum IgG, IgM and IgA levels in rheumatoid arthritis with vasculitis. The authors report a significant increase in the rheumatoid factor titre in rheumatoid arthritis patients with vasculitis. A significant rise in IgG and IgA levels was found in uncomplicated RA, when compared with a normal population. The IgM levels were not found to be elevated in this group of RA patients. In the RA patients with vasculitis, on the contrary, the three Ig classes are increased when compared with the normal population, and the IgM level is increased when compared with the uncomplicated RA group. Significant relation was found between log IgM and log R.F. titre in the RA group with vasculitis. It is shown that the mild reduction of serum (by dithiothreitol 0.004 M) causes a complete negativity of the R. F. in all cases. It is concluded that the haemagglutination and the latex precipitation in vitro are induced by IgM-R. F. and not by IgG and IgA-R. F. molecules. Only free sites of IgM-R.F. play a functional role in the determination of the R. F. -titre. The authors postulated that increase in IgM in RA patients with vasculitis is partially due to the presence of free IgM-R. F. molecules in serum. Finally it is concluded that hidden IgM-R. F. molecules in patients with lower R. F. titre are not quantified by immunodiffusion methods."} {"id": "PMID:1257705", "title": "Arthritis and hypogammaglobulinaemia. A. Family survey.", "content": "1. Hypogammaglobulinaemic patients admitted to the Medical Research Council's immunoglobulin therapy trials up to 1963 were examined for evidence of arthritis and were compared with population samples from Leigh, Wensleydale and Watford which were used as controls. 2. Four out of 60 males had inflammatory polyarthritis compared with an expected 0.4. In addition, 3 had synovitis limited to the knees and 4 had had polyarthritis in the past, the expected figures being 0.12 and 2.4 respectively. None of the patients had definite rheumatoid arthritis as defined by the American Rheumatism Association Criteria, though one satisfied the New York Criteria for Still's disease. All were seronegative and none of the patients with polyarthritis had radiological evidence of arthritis. None of the 18 female patients had arthritis. The prevalence of arthritis of synovitis in males was 29% in 1964, but in the following 3 years varied between 8 and 11%, suggesting a strong environmental influence. 3. All of the 7 males with inflammatory polyarthritis had levels of IgG, IgA, IgM and IgD, which were less than 30% of the standard normals and steatorrhoea was present in three. Steatorrhoea was also noted in 2 of 5 patients wih arthritis who died before the start of the survey, compared with 7% of all the males. 4. Clinical inflammatory polyarthritis was no more common in the first-degree relatives of patients with hypogammaglobulinaemia than in the population as a whole and they had no excess of erosive arthritis visible in X-rays of the hands or feet nor was sacro-iliitis excessively frequent. 5. Positive tests for rheumatoid factor were found in only 2 of the patients with hypogammaglobulinaemia and the first-degree relatives had no more positive sheep cell agglutination or latex fixation tests than expected in random population samples. 6. It is concluded that the seronegative polyarthritis which occurs in patients with hypogammaglobulinaemia is unrelated genetically to rheumatoid arthritis or Still's disease.", "contents": "Arthritis and hypogammaglobulinaemia. A. Family survey. 1. Hypogammaglobulinaemic patients admitted to the Medical Research Council's immunoglobulin therapy trials up to 1963 were examined for evidence of arthritis and were compared with population samples from Leigh, Wensleydale and Watford which were used as controls. 2. Four out of 60 males had inflammatory polyarthritis compared with an expected 0.4. In addition, 3 had synovitis limited to the knees and 4 had had polyarthritis in the past, the expected figures being 0.12 and 2.4 respectively. None of the patients had definite rheumatoid arthritis as defined by the American Rheumatism Association Criteria, though one satisfied the New York Criteria for Still's disease. All were seronegative and none of the patients with polyarthritis had radiological evidence of arthritis. None of the 18 female patients had arthritis. The prevalence of arthritis of synovitis in males was 29% in 1964, but in the following 3 years varied between 8 and 11%, suggesting a strong environmental influence. 3. All of the 7 males with inflammatory polyarthritis had levels of IgG, IgA, IgM and IgD, which were less than 30% of the standard normals and steatorrhoea was present in three. Steatorrhoea was also noted in 2 of 5 patients wih arthritis who died before the start of the survey, compared with 7% of all the males. 4. Clinical inflammatory polyarthritis was no more common in the first-degree relatives of patients with hypogammaglobulinaemia than in the population as a whole and they had no excess of erosive arthritis visible in X-rays of the hands or feet nor was sacro-iliitis excessively frequent. 5. Positive tests for rheumatoid factor were found in only 2 of the patients with hypogammaglobulinaemia and the first-degree relatives had no more positive sheep cell agglutination or latex fixation tests than expected in random population samples. 6. It is concluded that the seronegative polyarthritis which occurs in patients with hypogammaglobulinaemia is unrelated genetically to rheumatoid arthritis or Still's disease."} {"id": "PMID:1257706", "title": "Enzymes in intestinal mucosa from patients with rheumatoid diseases.", "content": "Jejunal mucosa from arthritic and control subjects was obtained by intraluminal biopsy or at operation and analysed for eight different enzymes. Histidinemethyl-esterase showed 6 to 10 times higher values in patients uith rheumatoid arthritis on comparison with control individuals in respective series. A disturbance in the histidine metabolism in these patients, possible depending on their intestinal flora, is discussed.", "contents": "Enzymes in intestinal mucosa from patients with rheumatoid diseases. Jejunal mucosa from arthritic and control subjects was obtained by intraluminal biopsy or at operation and analysed for eight different enzymes. Histidinemethyl-esterase showed 6 to 10 times higher values in patients uith rheumatoid arthritis on comparison with control individuals in respective series. A disturbance in the histidine metabolism in these patients, possible depending on their intestinal flora, is discussed."} {"id": "PMID:1257707", "title": "A study of the incidence of articular chondrocalcinosis in Paget's disease of bone.", "content": "Amongst 66 pagetic patients, whose average age (median) was 76 years, 9 cases of ACC were found. This represents an incidence of 13.6% of the whole group. Of 72 control subjects, whose average age (median) was 73 years, 7 were found to have ACC. This represents an overall incidence of 9.7% of the control group, but the difference is not statistically significant. From this study we conclude that ACC does not occur more frequently in Paget's disease than in a group of control subjects with the same age distribution.", "contents": "A study of the incidence of articular chondrocalcinosis in Paget's disease of bone. Amongst 66 pagetic patients, whose average age (median) was 76 years, 9 cases of ACC were found. This represents an incidence of 13.6% of the whole group. Of 72 control subjects, whose average age (median) was 73 years, 7 were found to have ACC. This represents an overall incidence of 9.7% of the control group, but the difference is not statistically significant. From this study we conclude that ACC does not occur more frequently in Paget's disease than in a group of control subjects with the same age distribution."} {"id": "PMID:1257708", "title": "Chloroquine treatment and bone changes in rheumatoid arthritis.", "content": "The effect of chloroquine on bone and articular cartilage was studied in 28 rheumatoid arthritis patients. After the administration of chloroquine for a minimum of 6 months, a metatarsal bone specimen was taken at operation. The control material consisted of 24 operated patients treated in the same way, except that they had not received chloroquine. Histological investigation, in which pairs of slides were compared in a blind test, revealed that the changes in the articular cartilage in those given chloroquine were less marked. Moreover, a diminished tendency to pannus formation and a more vigorous bone regeneration were observed in this group. Chloroquine seems thus to have a prophylactic effect on the articular cartilage changes in case of rheumatoid arthritis.", "contents": "Chloroquine treatment and bone changes in rheumatoid arthritis. The effect of chloroquine on bone and articular cartilage was studied in 28 rheumatoid arthritis patients. After the administration of chloroquine for a minimum of 6 months, a metatarsal bone specimen was taken at operation. The control material consisted of 24 operated patients treated in the same way, except that they had not received chloroquine. Histological investigation, in which pairs of slides were compared in a blind test, revealed that the changes in the articular cartilage in those given chloroquine were less marked. Moreover, a diminished tendency to pannus formation and a more vigorous bone regeneration were observed in this group. Chloroquine seems thus to have a prophylactic effect on the articular cartilage changes in case of rheumatoid arthritis."} {"id": "PMID:1257709", "title": "Retention and extra-articular spread of intra-articularly injected 90Y silicate.", "content": "A study was performed on the retention and distribution of intra-articularly injected colloidal 90Y silicate in 7 patients with rheumatoid arthritis (8 knees). In 5 knees retention was complete within the limits of measuring accuracy, and in the remaining 3, 82-84% was retained. No radioactivity was detected in the liver and heart areas or in the blood samples. The cumulative urine activity was less than 1.8%. In the inguinal lymph nodes, activity was detectable %0.5-2%) in only 3 cases. We conclude that 90Y silicate is a safe radioactive agent for the treatment of knee effusions, provided the limb is strictly immobilized after the injection.", "contents": "Retention and extra-articular spread of intra-articularly injected 90Y silicate. A study was performed on the retention and distribution of intra-articularly injected colloidal 90Y silicate in 7 patients with rheumatoid arthritis (8 knees). In 5 knees retention was complete within the limits of measuring accuracy, and in the remaining 3, 82-84% was retained. No radioactivity was detected in the liver and heart areas or in the blood samples. The cumulative urine activity was less than 1.8%. In the inguinal lymph nodes, activity was detectable %0.5-2%) in only 3 cases. We conclude that 90Y silicate is a safe radioactive agent for the treatment of knee effusions, provided the limb is strictly immobilized after the injection."} {"id": "PMID:1257710", "title": "Osmium deposits detected by x-ray after synoviorthesis of the knee.", "content": "A study of 113 knees of 72 patients treated with intra-articular injection of osmic acid for chronic exudative synovitis caused by various rheumatic diseases is reported. Certain cases presented abnormal radiological opacities, statistically more frequent after the injection of 200 mg than after 100 mg of osmic acid (33.9% and 15.7%). These images appear early after the injection and can remain for years. They should not be confused with intra-articular calcium deposits, or with synovial ossifications or various periosteal osteogenic processes. Their appearance does not seem to be related to the rheumatic disease treated or the therapeutic result obtained. They reflect the fixation of osmium in the synovial fatty tissue, which causes a fibrous reaction at this level. Their longterm action in the cicatrization of the synovia, or their part in a relapse of an inflammatory episode should be clarified.", "contents": "Osmium deposits detected by x-ray after synoviorthesis of the knee. A study of 113 knees of 72 patients treated with intra-articular injection of osmic acid for chronic exudative synovitis caused by various rheumatic diseases is reported. Certain cases presented abnormal radiological opacities, statistically more frequent after the injection of 200 mg than after 100 mg of osmic acid (33.9% and 15.7%). These images appear early after the injection and can remain for years. They should not be confused with intra-articular calcium deposits, or with synovial ossifications or various periosteal osteogenic processes. Their appearance does not seem to be related to the rheumatic disease treated or the therapeutic result obtained. They reflect the fixation of osmium in the synovial fatty tissue, which causes a fibrous reaction at this level. Their longterm action in the cicatrization of the synovia, or their part in a relapse of an inflammatory episode should be clarified."} {"id": "PMID:1257711", "title": "[Clinical pharmacokinetics].", "content": "The action of a drug depends on the quantity which reaches the site of its pharmacological action and how long it remains there. The necessary vital processes of the body dilute the active principle into different compartments of distribution, transform it into metabolites, and excrete it. Since a time duration of drug presence at the site of action is vital for the cure of disease, a comprehensive and quantitative expression of these time courses of drug distribution as a function of dose and route of administration is necessary for the establishment of proper dosage regimens for the treatment of disease and the avoidance of toxicities. The purpose of pharmacokinetics is to study these phenomena and to construct models suitable to explain them and to predict the behavior of drugs in conditions not yet studied. In this review some basic principles of pharmacokinetics (i.e. the compartment, the volume of distribution, the elimination half-life, etc.) are explained. Their clinical implications are shown in the case of multiple dose administration and in the study of the relations existing between blood levels of digoxin and the pharmacological action of this drug.", "contents": "[Clinical pharmacokinetics]. The action of a drug depends on the quantity which reaches the site of its pharmacological action and how long it remains there. The necessary vital processes of the body dilute the active principle into different compartments of distribution, transform it into metabolites, and excrete it. Since a time duration of drug presence at the site of action is vital for the cure of disease, a comprehensive and quantitative expression of these time courses of drug distribution as a function of dose and route of administration is necessary for the establishment of proper dosage regimens for the treatment of disease and the avoidance of toxicities. The purpose of pharmacokinetics is to study these phenomena and to construct models suitable to explain them and to predict the behavior of drugs in conditions not yet studied. In this review some basic principles of pharmacokinetics (i.e. the compartment, the volume of distribution, the elimination half-life, etc.) are explained. Their clinical implications are shown in the case of multiple dose administration and in the study of the relations existing between blood levels of digoxin and the pharmacological action of this drug."} {"id": "PMID:1257712", "title": "[The postoperative myocardial infarct in the surgical therapy of pelvic and leg arterial occlusions].", "content": "A total of 4063 surgical interventions for arterial occlusions of the lower limbs have been reviewed in a retrospective study. As compared to patients without specific diagnosis of preexisting coronary heart disease, the incidence of postoperative myocardial infarction is 10 times greater in the presence of clinical and electrocardiographic evidence of previous infarction; for patients suffering from typical angina pectoris the risk is 5 times higher and for patients with suspected preoperative infarction the incidence of postoperative infarction is 3 times that in surgical patients without such a history. The mortality rate from myocardial infarction occurring postoperatively in patients with no previous history of coronary heart disease is 26% as compared to 100% for patients who had sustained preoperative infarction. The rate of recurrence is significantly greater when the time interval between previous myocardial infarction and operation is less than three months. Comparison between elective and emergency cases shows that in the group undergoing emergency surgery the incidence of post-operative infarction is twice that under elective surgery, whereas mortality from myocardial infarction is 3 times higher following acute interventions. The problem of critical establishment of surgical indication, the need for accurate prior investigations and the requirement of adequate preoperative treatment are discussed.", "contents": "[The postoperative myocardial infarct in the surgical therapy of pelvic and leg arterial occlusions]. A total of 4063 surgical interventions for arterial occlusions of the lower limbs have been reviewed in a retrospective study. As compared to patients without specific diagnosis of preexisting coronary heart disease, the incidence of postoperative myocardial infarction is 10 times greater in the presence of clinical and electrocardiographic evidence of previous infarction; for patients suffering from typical angina pectoris the risk is 5 times higher and for patients with suspected preoperative infarction the incidence of postoperative infarction is 3 times that in surgical patients without such a history. The mortality rate from myocardial infarction occurring postoperatively in patients with no previous history of coronary heart disease is 26% as compared to 100% for patients who had sustained preoperative infarction. The rate of recurrence is significantly greater when the time interval between previous myocardial infarction and operation is less than three months. Comparison between elective and emergency cases shows that in the group undergoing emergency surgery the incidence of post-operative infarction is twice that under elective surgery, whereas mortality from myocardial infarction is 3 times higher following acute interventions. The problem of critical establishment of surgical indication, the need for accurate prior investigations and the requirement of adequate preoperative treatment are discussed."} {"id": "PMID:1257713", "title": "[Hypernephroid carcinoma and carcinoma of the urinary tract following phenacetin abuse].", "content": "From the 24 683 autopsies performed at the Institute of Pathology of Zurich University from 1963 to 1973, all cases with hypernephroid carcinoma or carcinoma of the urinary tract were listed. For each type of carcinoma the extent of phenacetin abuse, the sex and the mean age of the patients were established. The positive relationship between phenacetin abuse and carcinoma of the renal pelvis and the urinary bladder confirms the results of other investigators. In addition, a relationship between phenacetin abuse and hypernephroid carcinoma is discussed.", "contents": "[Hypernephroid carcinoma and carcinoma of the urinary tract following phenacetin abuse]. From the 24 683 autopsies performed at the Institute of Pathology of Zurich University from 1963 to 1973, all cases with hypernephroid carcinoma or carcinoma of the urinary tract were listed. For each type of carcinoma the extent of phenacetin abuse, the sex and the mean age of the patients were established. The positive relationship between phenacetin abuse and carcinoma of the renal pelvis and the urinary bladder confirms the results of other investigators. In addition, a relationship between phenacetin abuse and hypernephroid carcinoma is discussed."} {"id": "PMID:1257714", "title": "[Procedures for the early recognition of diabetics in Basle 1972. Contributions to the early diagnosis of diabetes mellitus by means of blood sugar analysis with special reference to the practical procedures under Swiss conditions].", "content": "In Basle in 1972 a diabetes survey was performed in subjects with increased risk of diabetes mellitus (overweight, age above 50, relatives of diabetics). For screening, the blood sugar was determined one hour after ingestion of 50 g of glucose. 404 males and 768 females (known diabetics excluded) were examined. One third of males and one quarter of females had a blood sugar value above 150 mg%. Blood sugar values of more than 200 mg% were found in 9% of the male and 7% of the female participants. A positive correlation existed between age and blood sugar values in males and females. Body weight and blood sugar value correlated only in females. However, in male subjects with pronounced obesity (Broca index greater than 1.23) there was a significantly higher incidence of blood sugar screening value above 150 mg% than in the rest of the males. It would appear that even slight overweight enhances glucose intolerance in females, whereas in males only marked overweight favours the manifestation of glucose intolerance. The cost of the detection of a new case of diabetes mellitus (blood sugar greater than 200 mg%) amounted to Sfr. 70.-. The Basle diabetes survey provides a model for successful conduct of a preventive program through cooperation of private organizations such as the local Medical Association and the local Diabetes Association.", "contents": "[Procedures for the early recognition of diabetics in Basle 1972. Contributions to the early diagnosis of diabetes mellitus by means of blood sugar analysis with special reference to the practical procedures under Swiss conditions]. In Basle in 1972 a diabetes survey was performed in subjects with increased risk of diabetes mellitus (overweight, age above 50, relatives of diabetics). For screening, the blood sugar was determined one hour after ingestion of 50 g of glucose. 404 males and 768 females (known diabetics excluded) were examined. One third of males and one quarter of females had a blood sugar value above 150 mg%. Blood sugar values of more than 200 mg% were found in 9% of the male and 7% of the female participants. A positive correlation existed between age and blood sugar values in males and females. Body weight and blood sugar value correlated only in females. However, in male subjects with pronounced obesity (Broca index greater than 1.23) there was a significantly higher incidence of blood sugar screening value above 150 mg% than in the rest of the males. It would appear that even slight overweight enhances glucose intolerance in females, whereas in males only marked overweight favours the manifestation of glucose intolerance. The cost of the detection of a new case of diabetes mellitus (blood sugar greater than 200 mg%) amounted to Sfr. 70.-. The Basle diabetes survey provides a model for successful conduct of a preventive program through cooperation of private organizations such as the local Medical Association and the local Diabetes Association."} {"id": "PMID:1257715", "title": "[Extranodular manifestations of generalized malignant lymphomas].", "content": "90 cases of malignant lymphoma in the autopsy material of the Institute of Pathology, University of Zurich (1970-1974) have been analyzed with reference to extranodular manifestations. 8% of the malignant lymphomas showed primary extranodular manifestations. The organs involved were (in decreasing order of importance) spleen, bone marrow, liver, kidneys, central nervous system, pancreas, adrenal glands, skin, lung and stomach. In 12% of cases only the lymphnodes were affected, whereas in the rest of the cases (80%) lymphnodes as well as extranodular organs were involved. In 78% of the malignant lymphomas the disease had had its origin in a solitary lymphnode or in a group of lymphnodes, the cervical lymphnodes predominating (30%). In 22% of the cases, extranodular organs (primarily the intestinal tract) had been the site of the primary clinical manifestations. The average time of survival was 17 months, including all grades of differentiation of the proliferating tumor cells. For the more unfavourable reticulum-cell type of malignant lymphoma the corresponding period was only 12.5 months.", "contents": "[Extranodular manifestations of generalized malignant lymphomas]. 90 cases of malignant lymphoma in the autopsy material of the Institute of Pathology, University of Zurich (1970-1974) have been analyzed with reference to extranodular manifestations. 8% of the malignant lymphomas showed primary extranodular manifestations. The organs involved were (in decreasing order of importance) spleen, bone marrow, liver, kidneys, central nervous system, pancreas, adrenal glands, skin, lung and stomach. In 12% of cases only the lymphnodes were affected, whereas in the rest of the cases (80%) lymphnodes as well as extranodular organs were involved. In 78% of the malignant lymphomas the disease had had its origin in a solitary lymphnode or in a group of lymphnodes, the cervical lymphnodes predominating (30%). In 22% of the cases, extranodular organs (primarily the intestinal tract) had been the site of the primary clinical manifestations. The average time of survival was 17 months, including all grades of differentiation of the proliferating tumor cells. For the more unfavourable reticulum-cell type of malignant lymphoma the corresponding period was only 12.5 months."} {"id": "PMID:1257716", "title": "[Frequency of amebiasis and other intestinal protozoal diseases. An epidemiological study with the aid of MIF technic].", "content": "Advantages and disadvantages of various laboratory techniques used for the diagnosis of intestinal protozoa are discussed. The importance of a correct parasitological diagnosis is emphasized. The MIF procedure has been investigated with regard to its reliability and found to be very effective due to its high diagnostic yield and reproducibility in repeated examinations. The incidence rates found in our material agreed well with those in the literature, thus enhancing the value of the MIF procedure. The feces of 1005 persons returning from the tropics during the first 8 months of 1975 have been examined by the MIF technique and assessed for intestinal protozoa. Apathogenic amebae were found four times as often as E. histolytica. The incidence was 52.7/1000 for E. histolytica and 70.6/1000 for Giardia lamblia. Multiple parasitosis is often diagnosed. E. histolytica is very likely to be encountered when two or three apathogenic amebae are present.", "contents": "[Frequency of amebiasis and other intestinal protozoal diseases. An epidemiological study with the aid of MIF technic]. Advantages and disadvantages of various laboratory techniques used for the diagnosis of intestinal protozoa are discussed. The importance of a correct parasitological diagnosis is emphasized. The MIF procedure has been investigated with regard to its reliability and found to be very effective due to its high diagnostic yield and reproducibility in repeated examinations. The incidence rates found in our material agreed well with those in the literature, thus enhancing the value of the MIF procedure. The feces of 1005 persons returning from the tropics during the first 8 months of 1975 have been examined by the MIF technique and assessed for intestinal protozoa. Apathogenic amebae were found four times as often as E. histolytica. The incidence was 52.7/1000 for E. histolytica and 70.6/1000 for Giardia lamblia. Multiple parasitosis is often diagnosed. E. histolytica is very likely to be encountered when two or three apathogenic amebae are present."} {"id": "PMID:1257717", "title": "[Surgical treatment of acute pancreatitis].", "content": "In the initial stage the treatment of acute pancreatitis must be medical. If there is not positive improvement after 2 to 6 days or in cases of associated cholelithiasis, surgery is indicated. The first step in surgery is a search for necrosis and hematomas, and their exact topographic localization. These findings will determine the final tactics, which may be drainage only, partial or exceptionally, total resection, or necrosectomy (which is not to be confused with a sequestrectomy !). Indications for these different types of operation are outlined and discussed. They are supplemented by large-scale drainage/lavage of the abdomen, choledocostomy or at least cholecystostomy, and temporary exclusion of the upper portion of the digestive tract. 30 personal cases treated according these principles are discussed.", "contents": "[Surgical treatment of acute pancreatitis]. In the initial stage the treatment of acute pancreatitis must be medical. If there is not positive improvement after 2 to 6 days or in cases of associated cholelithiasis, surgery is indicated. The first step in surgery is a search for necrosis and hematomas, and their exact topographic localization. These findings will determine the final tactics, which may be drainage only, partial or exceptionally, total resection, or necrosectomy (which is not to be confused with a sequestrectomy !). Indications for these different types of operation are outlined and discussed. They are supplemented by large-scale drainage/lavage of the abdomen, choledocostomy or at least cholecystostomy, and temporary exclusion of the upper portion of the digestive tract. 30 personal cases treated according these principles are discussed."} {"id": "PMID:1257718", "title": "[New therapeutic acquisitions in the surgery of the liver and bile ducts].", "content": "During these last years, there has not been sensational changes in biliary surgery, but rather a progressive improving of already known procedures. Conversely, the surgery of the liver has had a remarkable evolution. Even without mentioning transplantation, the possibility of resecting large parts of the gland with a reasonable risk demonstrates the progresses done these thirty last years. It is probable that technics introduced by liver transplant teams, such as bloodless resection by cold perfusion in situ, will allow to go even further in subtotal liver resection.", "contents": "[New therapeutic acquisitions in the surgery of the liver and bile ducts]. During these last years, there has not been sensational changes in biliary surgery, but rather a progressive improving of already known procedures. Conversely, the surgery of the liver has had a remarkable evolution. Even without mentioning transplantation, the possibility of resecting large parts of the gland with a reasonable risk demonstrates the progresses done these thirty last years. It is probable that technics introduced by liver transplant teams, such as bloodless resection by cold perfusion in situ, will allow to go even further in subtotal liver resection."} {"id": "PMID:1257719", "title": "[Malabsorption].", "content": "Various forms of malabsorption may be differntiated by quantitiative determination of fats, nitrogen and lactic acid in feces. Increased excretion of lactic acid may also be caused by bacterial degradation of intestinal mucus.", "contents": "[Malabsorption]. Various forms of malabsorption may be differntiated by quantitiative determination of fats, nitrogen and lactic acid in feces. Increased excretion of lactic acid may also be caused by bacterial degradation of intestinal mucus."} {"id": "PMID:1257720", "title": "[Effects of the environment on the liver and gastrointestinal tract].", "content": "The liver has a central role in the detoxication and elimination of toxic substances which enter the body as lipid-soluble compounds. Their transformation into polar watersoluble metabolites, termed biotransformation, is bound to the membranes of the smooth endoplasmatic reticulum. The oxidating enzyme in biotransformation can be induced by certain toxins and drugs. The chronic induction of enzymes by DDT and the consequences of this process of adaptation, particularly in regard to the metabolism of calcium is discussed. The protective effect of biotransformation and induction of enzymes against carcinogens, especially aflatoxin, are briefly reviewed. As examples of the chronic influence of vasotoxic substances, mention is mode of the veno-occlusive disease caused by the alkaloid phlorrhizidin found in plants, and the vinyl-chloride disease occurring in workers handling PVC. The first leads to portal hypertension of the post-sinusoidal type, while the second leads to pre- or intrasinusoidal portal hypertension and, after years of exposure, to hemangioendotheliosarcoma of the liver. The same tumor has been observed after arsenic intoxication. Arsenic may also lead to non-cirrhotic portal hypertension. The present opinions about environmentally induced gastrointestinal diseases are widely hypothetical. The high frequency of gastric carcinoma in Japan. and the varying occurrence of carcinoma of the colon in the civilized world in comparison with the rural population of tropical regions, is emphasized. The explanation for these facts is probably to be sought in differences of nutrition.", "contents": "[Effects of the environment on the liver and gastrointestinal tract]. The liver has a central role in the detoxication and elimination of toxic substances which enter the body as lipid-soluble compounds. Their transformation into polar watersoluble metabolites, termed biotransformation, is bound to the membranes of the smooth endoplasmatic reticulum. The oxidating enzyme in biotransformation can be induced by certain toxins and drugs. The chronic induction of enzymes by DDT and the consequences of this process of adaptation, particularly in regard to the metabolism of calcium is discussed. The protective effect of biotransformation and induction of enzymes against carcinogens, especially aflatoxin, are briefly reviewed. As examples of the chronic influence of vasotoxic substances, mention is mode of the veno-occlusive disease caused by the alkaloid phlorrhizidin found in plants, and the vinyl-chloride disease occurring in workers handling PVC. The first leads to portal hypertension of the post-sinusoidal type, while the second leads to pre- or intrasinusoidal portal hypertension and, after years of exposure, to hemangioendotheliosarcoma of the liver. The same tumor has been observed after arsenic intoxication. Arsenic may also lead to non-cirrhotic portal hypertension. The present opinions about environmentally induced gastrointestinal diseases are widely hypothetical. The high frequency of gastric carcinoma in Japan. and the varying occurrence of carcinoma of the colon in the civilized world in comparison with the rural population of tropical regions, is emphasized. The explanation for these facts is probably to be sought in differences of nutrition."} {"id": "PMID:1257721", "title": "[Can results in modern colonic surgery be improved? The results of 600 surgically treated colonic neoplasms].", "content": "Postoperative examination of 600 patients with carcinoma of the large bowel showed: 1. in emergency operation mortality is 30%, in elective surgery 10%; 2. operation risk in elderly patients is not significantly higher than in young patients; 3. only a decrease in \"patient and doctor delay\" and/or mass screening will provide better results.", "contents": "[Can results in modern colonic surgery be improved? The results of 600 surgically treated colonic neoplasms]. Postoperative examination of 600 patients with carcinoma of the large bowel showed: 1. in emergency operation mortality is 30%, in elective surgery 10%; 2. operation risk in elderly patients is not significantly higher than in young patients; 3. only a decrease in \"patient and doctor delay\" and/or mass screening will provide better results."} {"id": "PMID:1257722", "title": "[The hemoccult test in the screening for colonic carcinoma].", "content": "The only practicable method for mass screening for carcinoma of the colon is detection of occult blood in stool. In a coloscopically controlled study with the Haemoccult test, dependent from diet, 54-66% of polyps and 77-100% of carcinomas were detected. The Haemoccult test is therefore a suitable method for mass screening for colon carcinoma.", "contents": "[The hemoccult test in the screening for colonic carcinoma]. The only practicable method for mass screening for carcinoma of the colon is detection of occult blood in stool. In a coloscopically controlled study with the Haemoccult test, dependent from diet, 54-66% of polyps and 77-100% of carcinomas were detected. The Haemoccult test is therefore a suitable method for mass screening for colon carcinoma."} {"id": "PMID:1257723", "title": "[Calcitonin and salivary gland amylase secretion in vivo and in vitro. Preliminary report].", "content": "Synthetic human calcitonin stimulates amylase secretion of salivary glands in man. The same effect has been demonstrated in isolated cells of rat salivary glands. In vitro experiments suggest that the stimulatory effect is a direct action of calcitonin on salivary cells. Salivary secretion is not affected by pancreozymin or secretin. Our findings afford another example of the difference in secretory behaviour between salivary glands and pancreas.", "contents": "[Calcitonin and salivary gland amylase secretion in vivo and in vitro. Preliminary report]. Synthetic human calcitonin stimulates amylase secretion of salivary glands in man. The same effect has been demonstrated in isolated cells of rat salivary glands. In vitro experiments suggest that the stimulatory effect is a direct action of calcitonin on salivary cells. Salivary secretion is not affected by pancreozymin or secretin. Our findings afford another example of the difference in secretory behaviour between salivary glands and pancreas."} {"id": "PMID:1257724", "title": "[Is the \"exponential fitting\" in the stomach emptying curve justified?].", "content": "Gastric emptying of a solid meal labelled with 1 mCi99mTc-sulphur colloid has been studied with a gamma camera and computer in 5 healthy volunteers. The emptying process was analyzed for the three periods 0--30 min, 45--75 min, and 90-120 min after ingesting the meal. The half emptying time (T1/2) was calculated by exponential fitting for the three periods separately and an anlysis of variance of the regression slopes was performed. The nil hypothesis of no difference between the T1/2 calculated from the three periods was rejected at a level of significance of 0.01 in 13 out of 14 experiments. The authors discuss the practical implications of these findings for the use of T1/2 in the study of gastric emptying with labelled test meals.", "contents": "[Is the \"exponential fitting\" in the stomach emptying curve justified?]. Gastric emptying of a solid meal labelled with 1 mCi99mTc-sulphur colloid has been studied with a gamma camera and computer in 5 healthy volunteers. The emptying process was analyzed for the three periods 0--30 min, 45--75 min, and 90-120 min after ingesting the meal. The half emptying time (T1/2) was calculated by exponential fitting for the three periods separately and an anlysis of variance of the regression slopes was performed. The nil hypothesis of no difference between the T1/2 calculated from the three periods was rejected at a level of significance of 0.01 in 13 out of 14 experiments. The authors discuss the practical implications of these findings for the use of T1/2 in the study of gastric emptying with labelled test meals."} {"id": "PMID:1257725", "title": "[Behavior of serum gastrin under vagus stimulation with 2-deoxy-D-glucose with special reference to acid secretion and the mucosal histology].", "content": "Administration of 2-DG accompanied by simultaneous neutralization of gastric contents with sodium bicarbonate resulted in a rise in serum gastrin in 4 patients without gastric disease, 4 with duodenal ulcer and 4 with gastric ulcer. The rise in gastrin equals that observed on stimulation with meat extract. Patients with gastric ulcers display a low PAO and a small rise in gastrin compared with normals and patients with duodenal ulcers. This finding correlates well with the chronic atrophic changes of the antral mucosa in patients with gastric ulcer.", "contents": "[Behavior of serum gastrin under vagus stimulation with 2-deoxy-D-glucose with special reference to acid secretion and the mucosal histology]. Administration of 2-DG accompanied by simultaneous neutralization of gastric contents with sodium bicarbonate resulted in a rise in serum gastrin in 4 patients without gastric disease, 4 with duodenal ulcer and 4 with gastric ulcer. The rise in gastrin equals that observed on stimulation with meat extract. Patients with gastric ulcers display a low PAO and a small rise in gastrin compared with normals and patients with duodenal ulcers. This finding correlates well with the chronic atrophic changes of the antral mucosa in patients with gastric ulcer."} {"id": "PMID:1257726", "title": "[Effects of proximal gastric vagotomy (PVG) and total vagotomy (TV) on the coordination of the interdigestive myoelectric acitivity of the canine stomach and duodenum].", "content": "Interdigestive myoelectrical activity of the canine stomach and duodenum is organized in complexes of high-amplitude action potentials originating simultaneously in the stomach and duodenum every 80-180 minutes. This type of activity has been described as the \"interdigestive myoelectrical complex\" (IDMEC) by Szurszewski. The present work was undertaken to elucidate the role of the vagus nerve in control of the IDMEC. Dogs were prepared with chronically implanted Ag-AgCl-electrodes on the stomach and duodenum. Fasting myoelectrical activity was recorded in the normal animal, after proximal gastric vagotomy (PGV), and after truncal vagotomy (TV). PGV did not affect the IDMEC, but TV abolished the pattern for the period of observation (3 months). The authors discuss the possible role of interference by TV with gastrodeuodenal interdigestive motor activity in the pathogenesis of reflux gastritis after vagotomy and drainage.", "contents": "[Effects of proximal gastric vagotomy (PVG) and total vagotomy (TV) on the coordination of the interdigestive myoelectric acitivity of the canine stomach and duodenum]. Interdigestive myoelectrical activity of the canine stomach and duodenum is organized in complexes of high-amplitude action potentials originating simultaneously in the stomach and duodenum every 80-180 minutes. This type of activity has been described as the \"interdigestive myoelectrical complex\" (IDMEC) by Szurszewski. The present work was undertaken to elucidate the role of the vagus nerve in control of the IDMEC. Dogs were prepared with chronically implanted Ag-AgCl-electrodes on the stomach and duodenum. Fasting myoelectrical activity was recorded in the normal animal, after proximal gastric vagotomy (PGV), and after truncal vagotomy (TV). PGV did not affect the IDMEC, but TV abolished the pattern for the period of observation (3 months). The authors discuss the possible role of interference by TV with gastrodeuodenal interdigestive motor activity in the pathogenesis of reflux gastritis after vagotomy and drainage."} {"id": "PMID:1257727", "title": "[Exocrine pancreatic function, intestinal resorption and reaction to Vibrio cholerae infection in protein deficiency].", "content": "Six Patas monkeys were fed a protein-free diet while 16 animals of the same species receoved a standard monkey diet. The protein-depleted monkeys showed reduced absorption of folic acid but not Dxylose, and 5 out of 6 exhibited depressed exocrine pancreatic function. When challenged with Vibrio cholerae, animals with reduced folic acid absorption and pancreatic enzyme production excreted the micro-organisms for a longer time.", "contents": "[Exocrine pancreatic function, intestinal resorption and reaction to Vibrio cholerae infection in protein deficiency]. Six Patas monkeys were fed a protein-free diet while 16 animals of the same species receoved a standard monkey diet. The protein-depleted monkeys showed reduced absorption of folic acid but not Dxylose, and 5 out of 6 exhibited depressed exocrine pancreatic function. When challenged with Vibrio cholerae, animals with reduced folic acid absorption and pancreatic enzyme production excreted the micro-organisms for a longer time."} {"id": "PMID:1257728", "title": "[Delay in the diagnosis of stomach neoplasms: consequences in 534 cases].", "content": "\"Patient delay\" in carcinoma of the stomach has been, in the past 10 years, 4 months on average. However, \"doctor delay\" has increased from 10 weeks to 8 months. A shortening of \"doctor delay\" is possible only if early endoscopy is carried out.", "contents": "[Delay in the diagnosis of stomach neoplasms: consequences in 534 cases]. \"Patient delay\" in carcinoma of the stomach has been, in the past 10 years, 4 months on average. However, \"doctor delay\" has increased from 10 weeks to 8 months. A shortening of \"doctor delay\" is possible only if early endoscopy is carried out."} {"id": "PMID:1257729", "title": "[The use of impedance measurements in the colon].", "content": "Biological changes in tissue also affect its biophysical and consequently its electrical properties. By the method here described, high-frequency current is caused to flow through the tissue under examination and the voltage decrease is measured. Measuring equipment of the author's own design has been developed for routine use of the method. The results of repeated measurements in the rectum of 323 subjects show that malignant tumor always cause lesser voltage decreases than do intact or inflamed tissues. The method has already been used during coloscopy in 40 patients. The results were in full agreement with biopsy findings.", "contents": "[The use of impedance measurements in the colon]. Biological changes in tissue also affect its biophysical and consequently its electrical properties. By the method here described, high-frequency current is caused to flow through the tissue under examination and the voltage decrease is measured. Measuring equipment of the author's own design has been developed for routine use of the method. The results of repeated measurements in the rectum of 323 subjects show that malignant tumor always cause lesser voltage decreases than do intact or inflamed tissues. The method has already been used during coloscopy in 40 patients. The results were in full agreement with biopsy findings."} {"id": "PMID:1257730", "title": "[The value of endoscopic retrograde cholangiopancreatography in negative or undetermined cholecystocholangiography].", "content": "In 299 patients with negative cholecystocholangiogram, endoscopic retrograde cholangio-pancreatography (ERCP) was performed. In obstructive jaundice ERCP is the method of choice, while in cholestasis it is indicated if the intravenous cholecystocholangiogram is insufficient. In unclear abdominal conditions and in \"postcholecystectomy syndrome\" ERCP may be carried out after other abdominal diseases have been ruled out.", "contents": "[The value of endoscopic retrograde cholangiopancreatography in negative or undetermined cholecystocholangiography]. In 299 patients with negative cholecystocholangiogram, endoscopic retrograde cholangio-pancreatography (ERCP) was performed. In obstructive jaundice ERCP is the method of choice, while in cholestasis it is indicated if the intravenous cholecystocholangiogram is insufficient. In unclear abdominal conditions and in \"postcholecystectomy syndrome\" ERCP may be carried out after other abdominal diseases have been ruled out."} {"id": "PMID:1257731", "title": "[Diagnosis of treated and untreated chronic-aggressive hepatitis].", "content": "A total of 121 patients with chronic active hepatitis (CAH) of two Zurich hospitals were controlled over a mean time of 5 years and 4 months. All patients of one hospital were consequently treated with corticosteroids and azathioprine, whereas those of the other hospital were not treated unless a severe deterioration occurred. In this case treatment was as short as possible. Results indicate that long - time treatment of CAH results in better prognosis than does no or short - time treatment. Death rate per observed patient - year was 0.079 in the no - therapy group, 0.035 in the short - therapy group and 0.025 in the long - time therapy group.", "contents": "[Diagnosis of treated and untreated chronic-aggressive hepatitis]. A total of 121 patients with chronic active hepatitis (CAH) of two Zurich hospitals were controlled over a mean time of 5 years and 4 months. All patients of one hospital were consequently treated with corticosteroids and azathioprine, whereas those of the other hospital were not treated unless a severe deterioration occurred. In this case treatment was as short as possible. Results indicate that long - time treatment of CAH results in better prognosis than does no or short - time treatment. Death rate per observed patient - year was 0.079 in the no - therapy group, 0.035 in the short - therapy group and 0.025 in the long - time therapy group."} {"id": "PMID:1257736", "title": "Oxprenolol in hypertension: a report on 2,770 patients in general practice originally treated with methyldopa.", "content": "Substitution, in part of totally, of the non-selective beta-receptor antagonist oxprenolol for methyldopa in 2,770 treated hypertensive patients resulted in a significant reduction in blood pressure levels and a considerable improvement in the quality of the patient's life.", "contents": "Oxprenolol in hypertension: a report on 2,770 patients in general practice originally treated with methyldopa. Substitution, in part of totally, of the non-selective beta-receptor antagonist oxprenolol for methyldopa in 2,770 treated hypertensive patients resulted in a significant reduction in blood pressure levels and a considerable improvement in the quality of the patient's life."} {"id": "PMID:1257737", "title": "Detection of breast disease in a family planning association clinic.", "content": "The incidence and prevalence of disorders of the breast have been assessed in 13,456 women examined annually at a family planning clinic over 5 years. Screening for disorders of the breast was by clinical examination alone and abnormalities were detected in 1 of every 58 women attending the clinic and these were referred for hospital opinion: biopsy was required in 1 in 114. Only 12 cancers of the breast were detected and all of these in women over 35 years. It is suggested that the usual policy of examining the breasts of women taking oral contraceptive preparations should be restricted to those over 40 years.", "contents": "Detection of breast disease in a family planning association clinic. The incidence and prevalence of disorders of the breast have been assessed in 13,456 women examined annually at a family planning clinic over 5 years. Screening for disorders of the breast was by clinical examination alone and abnormalities were detected in 1 of every 58 women attending the clinic and these were referred for hospital opinion: biopsy was required in 1 in 114. Only 12 cancers of the breast were detected and all of these in women over 35 years. It is suggested that the usual policy of examining the breasts of women taking oral contraceptive preparations should be restricted to those over 40 years."} {"id": "PMID:1257741", "title": "X-ray microscopy of biological objects with carbon kappa and with synchrotron radiation.", "content": "X-ray micrographs of biological objects have been obtained with a resolution better than 1000 angstroms by using poly(methyl methacrylate) x-ray resist and carbon Kalpha or synchrotron radiation. Synchrotron radiation allows short exposure times; storage rings especially designed as radiation sources and improved x-ray resists would make exposure times under 1 second possible.", "contents": "X-ray microscopy of biological objects with carbon kappa and with synchrotron radiation. X-ray micrographs of biological objects have been obtained with a resolution better than 1000 angstroms by using poly(methyl methacrylate) x-ray resist and carbon Kalpha or synchrotron radiation. Synchrotron radiation allows short exposure times; storage rings especially designed as radiation sources and improved x-ray resists would make exposure times under 1 second possible."} {"id": "PMID:1257742", "title": "Opsin structure probed by raman spectroscopy of photoreceptor membranes.", "content": "The first nonresonance Raman spectra of photoreceptor membranes are presented. Information about the membrane protein, opsin, and the membrane phospholipids can be deduced. Opsin appears to contain alpha-helical structure but little beta structure. The tyrosine residues are predominantly hydrogen bonded, and disulfide bonds, if they are present, are not in the normal gauche-gauche configuration.", "contents": "Opsin structure probed by raman spectroscopy of photoreceptor membranes. The first nonresonance Raman spectra of photoreceptor membranes are presented. Information about the membrane protein, opsin, and the membrane phospholipids can be deduced. Opsin appears to contain alpha-helical structure but little beta structure. The tyrosine residues are predominantly hydrogen bonded, and disulfide bonds, if they are present, are not in the normal gauche-gauche configuration."} {"id": "PMID:1257743", "title": "Lateral preoptic lesions in rats separate urge to drink from amount of water drunk.", "content": "Rats with bilaterally symmetrical lesions in the laterla preoptic area do not drink after acute intracellular dehydration, but they drink normally after water deprivation. They, like normal rats, also drink more when cellular dehydration is superimposed upon water deprivation. Unlike normal rats, however, rats with lesions in the lateral preoptic area do not increase their rate of lever-pressing in response to the combined stimulus. Thus, the urge to drink can be separated from the amount of fluid drunk.", "contents": "Lateral preoptic lesions in rats separate urge to drink from amount of water drunk. Rats with bilaterally symmetrical lesions in the laterla preoptic area do not drink after acute intracellular dehydration, but they drink normally after water deprivation. They, like normal rats, also drink more when cellular dehydration is superimposed upon water deprivation. Unlike normal rats, however, rats with lesions in the lateral preoptic area do not increase their rate of lever-pressing in response to the combined stimulus. Thus, the urge to drink can be separated from the amount of fluid drunk."} {"id": "PMID:1257744", "title": "Human Y-chromosome-specific reiterated DNA.", "content": "Radiolabeled reiterated DNA specific for the human Y chromosome has been obtained by extensive reassociations between [3H]DNA prepared from men and excess DNA from women. These highly purifed labeled sequences reassociate only with DNA from individuals with a Y chromosome. The percentage of Y-chromosome-specific DNA isolated from individuals with differing numbers of Y chromosomes is a function of the number of chromosomes present. The purifed Y-chromosome-specific sequences may represent between 7 and 11 percent of the human Y chromosome.", "contents": "Human Y-chromosome-specific reiterated DNA. Radiolabeled reiterated DNA specific for the human Y chromosome has been obtained by extensive reassociations between [3H]DNA prepared from men and excess DNA from women. These highly purifed labeled sequences reassociate only with DNA from individuals with a Y chromosome. The percentage of Y-chromosome-specific DNA isolated from individuals with differing numbers of Y chromosomes is a function of the number of chromosomes present. The purifed Y-chromosome-specific sequences may represent between 7 and 11 percent of the human Y chromosome."} {"id": "PMID:1257745", "title": "Elimination of the sarcoma genome from murine sarcoma virus transformed cat cells.", "content": "Cat cells transformed by Moloney murine sarcoma virus contain virus-specific sequences in their RNA and DNA. Cloned, spontaneous revertant cell lines derived from clones of these cells had no evidence of the sarcoma genome in the cell RNA or DNA as judged by RNA-complementary DNA or DNA-complementary DNA hybridizations. ?This is apparently the first report of loss of a transforming genome in a revertant cell line.", "contents": "Elimination of the sarcoma genome from murine sarcoma virus transformed cat cells. Cat cells transformed by Moloney murine sarcoma virus contain virus-specific sequences in their RNA and DNA. Cloned, spontaneous revertant cell lines derived from clones of these cells had no evidence of the sarcoma genome in the cell RNA or DNA as judged by RNA-complementary DNA or DNA-complementary DNA hybridizations. ?This is apparently the first report of loss of a transforming genome in a revertant cell line."} {"id": "PMID:1257747", "title": "Prostaglandin B1: the L-shaped prostaglandin.", "content": "The crystal and molecular structure of prostaglandin B1( PGB1) has been determined. The conformation is L-shaped, with the alpha and omega side chains roughly perpendicular to one another. This arrangement differs from the \"hairpin\" or approximately parallel disposition of side chains observed for other prostaglandins. The omega chain, which normally turns at the 15-hydroxyl back toward the alpha chain, is fully extended. The conformation is stabilized by the conjugation of the dienone chromophore. The 15-hydroxyl, which is normally directed away from the centroid of the prostaglandin in the hairpin model, is turned inward in L-shaped PGB1. The low biological activity of PGB1 in many systems and especially its inhibition of the metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase may be attributable directly to the observed L-shape conformation.", "contents": "Prostaglandin B1: the L-shaped prostaglandin. The crystal and molecular structure of prostaglandin B1( PGB1) has been determined. The conformation is L-shaped, with the alpha and omega side chains roughly perpendicular to one another. This arrangement differs from the \"hairpin\" or approximately parallel disposition of side chains observed for other prostaglandins. The omega chain, which normally turns at the 15-hydroxyl back toward the alpha chain, is fully extended. The conformation is stabilized by the conjugation of the dienone chromophore. The 15-hydroxyl, which is normally directed away from the centroid of the prostaglandin in the hairpin model, is turned inward in L-shaped PGB1. The low biological activity of PGB1 in many systems and especially its inhibition of the metabolizing enzyme 15-hydroxyprostaglandin dehydrogenase may be attributable directly to the observed L-shape conformation."} {"id": "PMID:1257748", "title": "Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats.", "content": "Rats learned to press a lever for intravenous injections of amphetamine or apomorphine. They also learned to avoid the taste of saccharin which was associated with experimenter-administered amphetamine or with self-administered apomorphine. Thus these, and presumably other, self-administered drugs serve as compound pharmacological stimuli, having both positively reinforcing and aversive properties.", "contents": "Both positive reinforcement and conditioned aversion from amphetamine and from apomorphine in rats. Rats learned to press a lever for intravenous injections of amphetamine or apomorphine. They also learned to avoid the taste of saccharin which was associated with experimenter-administered amphetamine or with self-administered apomorphine. Thus these, and presumably other, self-administered drugs serve as compound pharmacological stimuli, having both positively reinforcing and aversive properties."} {"id": "PMID:1257749", "title": "Marine oscillatoria (Trichodesmium): explanation for aerobic nitrogen fixation without heterocysts.", "content": "Nitrogen fixation in marine Oscillatoria appears to be associated with differentiated cells located in the center of the colony. These central cells exhibit reduced pigmentation relative to peripherally located cells and do not incorporate 14CO2 in photosynthesis. Central cells apparently do not produce O2 which would deactivate nitrogenase. When central cells are exposed to O2 via disruption of the colonies, N2 fixation (acetylene reduction) decreases sharply even though individual trichomes remain intact. Disruption of colonies in the absence of O2 does not cause reduced nitrogenase activity. In the sea, turbulence from wave action apparently separates trichomes allowing O2 to enter thus decreasing nitrogenase activity. These observations explain how Oscillatoria is able to fix N2 without heterocysts in an aerobic environment and why it blooms virtually always occur in calm seas.", "contents": "Marine oscillatoria (Trichodesmium): explanation for aerobic nitrogen fixation without heterocysts. Nitrogen fixation in marine Oscillatoria appears to be associated with differentiated cells located in the center of the colony. These central cells exhibit reduced pigmentation relative to peripherally located cells and do not incorporate 14CO2 in photosynthesis. Central cells apparently do not produce O2 which would deactivate nitrogenase. When central cells are exposed to O2 via disruption of the colonies, N2 fixation (acetylene reduction) decreases sharply even though individual trichomes remain intact. Disruption of colonies in the absence of O2 does not cause reduced nitrogenase activity. In the sea, turbulence from wave action apparently separates trichomes allowing O2 to enter thus decreasing nitrogenase activity. These observations explain how Oscillatoria is able to fix N2 without heterocysts in an aerobic environment and why it blooms virtually always occur in calm seas."} {"id": "PMID:1257750", "title": "Pattern-analyzing memory.", "content": "College students reread text after an interval of 13 to 15 months more rapidly than they read new matter taken from the same sources. The results implicate a memory system at the level of pattern analysis that seems to be distinguishable from memory of syntactic and semantic features of text.", "contents": "Pattern-analyzing memory. College students reread text after an interval of 13 to 15 months more rapidly than they read new matter taken from the same sources. The results implicate a memory system at the level of pattern analysis that seems to be distinguishable from memory of syntactic and semantic features of text."} {"id": "PMID:1257751", "title": "beta-D-galactosidase activity in single yeast cells during cell cycle of Saccharomyces lactis.", "content": "Single Saccharomyces lactis cells taken from a random population were assayed for beta-D-galactosidase activity under a microscope equipped for fluorogenic measurements. The cells were also photographed, and enzymatic activity was correlated to the size of cell buds. A perodic pattern of enzyme synthesis was found during the cell cycle.", "contents": "beta-D-galactosidase activity in single yeast cells during cell cycle of Saccharomyces lactis. Single Saccharomyces lactis cells taken from a random population were assayed for beta-D-galactosidase activity under a microscope equipped for fluorogenic measurements. The cells were also photographed, and enzymatic activity was correlated to the size of cell buds. A perodic pattern of enzyme synthesis was found during the cell cycle."} {"id": "PMID:1257753", "title": "Meaning, memory structure, and mental processes.", "content": "Although people experience little difficulty in recognizing printed words and comprehending sentences, they cannot do it instantaneously. Experimental psychologists have recently measured the speed of these mental processes by applying a reaction-time method. The method provides new data concerning the organization and retrieval of familiar semantic information in human memory. It has been found that close relations between the meanings of words help people to recognize and pronounce the words faster, especially when the words are hard to see because of visual distortions. Close relations between word meanings also facilitate the comprehension of some sentences, as indicated by how long a person takes to decide whether the sentences are true or false. The facilitation is not universal, however. When the relation between the meanings of two words must be analyzed carefully, their proximity may actually inhibit mental processing. These results, along with additional findings, support the hypothesis that human memory includes a semantic network that represents various categories of objects at distinct locations linked to specify their relations with each other. The memory structure probably influences a number of different mental processes that use it. One possible access route to the network is through a set of detectors designed to accumulate sensory information and signal the presence of particular words. There also appear to be processes for searching and comparing pieces of knowledge after a person finds the memory locations of designated categories. Further research using the reaction-time method may provide a more detailed inventory of what facts are retrieved directly from memory and what are computed from other stored information (36).", "contents": "Meaning, memory structure, and mental processes. Although people experience little difficulty in recognizing printed words and comprehending sentences, they cannot do it instantaneously. Experimental psychologists have recently measured the speed of these mental processes by applying a reaction-time method. The method provides new data concerning the organization and retrieval of familiar semantic information in human memory. It has been found that close relations between the meanings of words help people to recognize and pronounce the words faster, especially when the words are hard to see because of visual distortions. Close relations between word meanings also facilitate the comprehension of some sentences, as indicated by how long a person takes to decide whether the sentences are true or false. The facilitation is not universal, however. When the relation between the meanings of two words must be analyzed carefully, their proximity may actually inhibit mental processing. These results, along with additional findings, support the hypothesis that human memory includes a semantic network that represents various categories of objects at distinct locations linked to specify their relations with each other. The memory structure probably influences a number of different mental processes that use it. One possible access route to the network is through a set of detectors designed to accumulate sensory information and signal the presence of particular words. There also appear to be processes for searching and comparing pieces of knowledge after a person finds the memory locations of designated categories. Further research using the reaction-time method may provide a more detailed inventory of what facts are retrieved directly from memory and what are computed from other stored information (36)."} {"id": "PMID:1257754", "title": "Sex pheromone specificity in the pine sawflies: interchange of acid moieties in an ester.", "content": "3,7-Dimethylpentadecan-2-ol was identified as the free alcohol in three species from two genera of pine sawflies (Hymenoptera: Diprionidae). In Neodiprion lecontei and Neodiprion sertifer the acetate of this alcohol is the major component of their sex attractant; in Diprion similis it is the propionate. By examining the responses of the male antennae of several species of Neodiprion through the electroantennographic technique, it was determined that four species responded to the acetate and six to the propionate.", "contents": "Sex pheromone specificity in the pine sawflies: interchange of acid moieties in an ester. 3,7-Dimethylpentadecan-2-ol was identified as the free alcohol in three species from two genera of pine sawflies (Hymenoptera: Diprionidae). In Neodiprion lecontei and Neodiprion sertifer the acetate of this alcohol is the major component of their sex attractant; in Diprion similis it is the propionate. By examining the responses of the male antennae of several species of Neodiprion through the electroantennographic technique, it was determined that four species responded to the acetate and six to the propionate."} {"id": "PMID:1257755", "title": "Nonenzymic joining of oligoadenylates on a polyuridylic acid template.", "content": "3',5'-Linked hexa-adenylic acid with a 2',3'-cyclic phosphate terminus [(A5A less than p] couples on a polyuridylic acid template in the presence of ethylenediamine to form the dodecamer (24 percent) and octadecamer (5 percent). The bond produced is largely that of the 2',5' isomer.", "contents": "Nonenzymic joining of oligoadenylates on a polyuridylic acid template. 3',5'-Linked hexa-adenylic acid with a 2',3'-cyclic phosphate terminus [(A5A less than p] couples on a polyuridylic acid template in the presence of ethylenediamine to form the dodecamer (24 percent) and octadecamer (5 percent). The bond produced is largely that of the 2',5' isomer."} {"id": "PMID:1257756", "title": "Insect photoperiodism: the \"T experiment\" as evidence for an hourglass mechanism.", "content": "\"T experiments\" demonstrate that the clock controlling termination of larval diapause in Ostrinia nubilalis is an hourglass mechanism that measures 8 hours of darkness. Circadian oscillations are not involved in photoperiodic time measurement in this species.", "contents": "Insect photoperiodism: the \"T experiment\" as evidence for an hourglass mechanism. \"T experiments\" demonstrate that the clock controlling termination of larval diapause in Ostrinia nubilalis is an hourglass mechanism that measures 8 hours of darkness. Circadian oscillations are not involved in photoperiodic time measurement in this species."} {"id": "PMID:1257757", "title": "Tin: a potent inducer of heme oxygenase in kidney.", "content": "Tin greatly enhances heme breakdown in kidney, thus impairing heme-dependent cellular functions, such as cytochrome P-450 mediated drug biotransformation. This novel action of the metal results from a potent induction effect on heme oxygenase, the enzyme that catalyzes heme oxidation in microsomes. The possible toxicological implications of this tin effect in the kidney merit further investigation.", "contents": "Tin: a potent inducer of heme oxygenase in kidney. Tin greatly enhances heme breakdown in kidney, thus impairing heme-dependent cellular functions, such as cytochrome P-450 mediated drug biotransformation. This novel action of the metal results from a potent induction effect on heme oxygenase, the enzyme that catalyzes heme oxidation in microsomes. The possible toxicological implications of this tin effect in the kidney merit further investigation."} {"id": "PMID:1257758", "title": "Reinvestigation of oak leaf roller sex pheromone components and the hypothesis that they vary with diet.", "content": "The sex pheromone of the oak leaf roller, Archips semiferanus, was identified as a specific blend (67:33) of trans-11- and cis-11-tetradecenyl acetates. The pheromone blend of females from a semisynthetic diet and from three oak species did not vary significantly. Males from these diets responsded in the laboratory and the field only to treatments approximating the 67 : 33 blend. These findings conflict with the hypothesis that the composition and perception of month sex pheromones vary with slight changes in diet.", "contents": "Reinvestigation of oak leaf roller sex pheromone components and the hypothesis that they vary with diet. The sex pheromone of the oak leaf roller, Archips semiferanus, was identified as a specific blend (67:33) of trans-11- and cis-11-tetradecenyl acetates. The pheromone blend of females from a semisynthetic diet and from three oak species did not vary significantly. Males from these diets responsded in the laboratory and the field only to treatments approximating the 67 : 33 blend. These findings conflict with the hypothesis that the composition and perception of month sex pheromones vary with slight changes in diet."} {"id": "PMID:1257759", "title": "Insect phermones: diet related?", "content": "The question of the origin of insect pheromones is discussed in the light of new published information on the communication system of the oak leaf roller. It is concluded that compounds found in diets may be partially responsible for insect sexual behavior and that substructuring of insect populations in ecological and evolutionary time through dietary chemicals remains a hypothesis worthy of further testing.", "contents": "Insect phermones: diet related? The question of the origin of insect pheromones is discussed in the light of new published information on the communication system of the oak leaf roller. It is concluded that compounds found in diets may be partially responsible for insect sexual behavior and that substructuring of insect populations in ecological and evolutionary time through dietary chemicals remains a hypothesis worthy of further testing."} {"id": "PMID:1257760", "title": "Spatial frequency-contingent color aftereffects.", "content": "Two-dimensional Fourier analysis of checkerboards reveals that major components are at a 45 degree angle to the check edges. After adapting to chromatic checkerboards, subjects who viewed achromatic grating stimuli reported that complementary color aftereffects are aligned with spatial frequency components rather than with the edges in the pattern.", "contents": "Spatial frequency-contingent color aftereffects. Two-dimensional Fourier analysis of checkerboards reveals that major components are at a 45 degree angle to the check edges. After adapting to chromatic checkerboards, subjects who viewed achromatic grating stimuli reported that complementary color aftereffects are aligned with spatial frequency components rather than with the edges in the pattern."} {"id": "PMID:1257761", "title": "A comparison of Fourier analysis and feature analysis in pattern-specific color aftereffects.", "content": "Subjects were adapted to alternating upright red and oblique green checkerboards. After adaptation, vertical and horizontal gratings appeared pink and oblique gratings appeared green. The results show an orientation and spatial frequency selectivity predicted by two-dimensional Fourier analysis.", "contents": "A comparison of Fourier analysis and feature analysis in pattern-specific color aftereffects. Subjects were adapted to alternating upright red and oblique green checkerboards. After adaptation, vertical and horizontal gratings appeared pink and oblique gratings appeared green. The results show an orientation and spatial frequency selectivity predicted by two-dimensional Fourier analysis."} {"id": "PMID:1257762", "title": "Introversion/extroversion, time stress, and caffeine: effect on verbal performance.", "content": "Time pressure and caffeine differentially affected the performance of introverts on verbal ability tests similar to the Graduate Record Examination. With time pressure and 200 milligrams of caffeine, the performance of introverts fell by 0.63 standard deviation, but extroverts by 0.44 standard deviation.", "contents": "Introversion/extroversion, time stress, and caffeine: effect on verbal performance. Time pressure and caffeine differentially affected the performance of introverts on verbal ability tests similar to the Graduate Record Examination. With time pressure and 200 milligrams of caffeine, the performance of introverts fell by 0.63 standard deviation, but extroverts by 0.44 standard deviation."} {"id": "PMID:1257763", "title": "Lead poisoning: altered urinary catecholamine metabolites as indicators of intoxication in mice and children.", "content": "Whether neuropsychological impairment occurs in children with increased lead absorption who are without clinical symptoms is of current concern. This tissue, which involves potentially large numbers of children, remains unresolved, in part because of the lack of sensitive biochemical indicators of the effects of lead on the nervous system. In experimental subclinical lead poisoning in mice, significant increases in homovanillic acid and vanillylmandelic acid have been found in brain and urine. In children with increased lead absorption, these acids were meaured in urine collected quantitatively under controlled dietary conditions; preliminary results show fivefold increases in the daily output of these compounds. These data suggest that the altered catecholamine metabolism also occurs in children.", "contents": "Lead poisoning: altered urinary catecholamine metabolites as indicators of intoxication in mice and children. Whether neuropsychological impairment occurs in children with increased lead absorption who are without clinical symptoms is of current concern. This tissue, which involves potentially large numbers of children, remains unresolved, in part because of the lack of sensitive biochemical indicators of the effects of lead on the nervous system. In experimental subclinical lead poisoning in mice, significant increases in homovanillic acid and vanillylmandelic acid have been found in brain and urine. In children with increased lead absorption, these acids were meaured in urine collected quantitatively under controlled dietary conditions; preliminary results show fivefold increases in the daily output of these compounds. These data suggest that the altered catecholamine metabolism also occurs in children."} {"id": "PMID:1257764", "title": "A novel means for dealing with L-canavanine, a toxic metabolite.", "content": "L-canavanine is a highly toxic L-arginine analog found in some leguminous seeds. Larvae of the bruchid beetle Caryedes brasiliensis, collected in Costa Rica, subsist solely on tissues of the mature seed of Dioclea megacarpa, which contains more than 8 percent L-canavanine by dry weight. The arginyl-tRNA synthetase of the bruchid beetle larvae discriminates between L-arginine and L-canavanine, and canavanyl proteins are not synthesized. In this way, bruchid beetle larvae avoid an adverse biochemical effect of L-canavanine.", "contents": "A novel means for dealing with L-canavanine, a toxic metabolite. L-canavanine is a highly toxic L-arginine analog found in some leguminous seeds. Larvae of the bruchid beetle Caryedes brasiliensis, collected in Costa Rica, subsist solely on tissues of the mature seed of Dioclea megacarpa, which contains more than 8 percent L-canavanine by dry weight. The arginyl-tRNA synthetase of the bruchid beetle larvae discriminates between L-arginine and L-canavanine, and canavanyl proteins are not synthesized. In this way, bruchid beetle larvae avoid an adverse biochemical effect of L-canavanine."} {"id": "PMID:1257766", "title": "Morphine-induced rotation in naive, nonlesioned rats.", "content": "In rats injected with morphine in the midbrain reticular formation, pronounced ipsilateral rotation behavior was elicited by mild auditory and visual stimuli. The frequency of occurrence and rate of rotation were dose-dependent. This effect was site specific and drug specific; other drugs (except heroin) failed to induce this behavior. Naloxone potentiated the morphine rotation. Pretreatment with drugs that either potentiated or attenuated the morphine rotation indicated involvement of the noradrenergic and cholinergic systems and excluded a role for the dopaminergic system. No analgesia was observed after morphine microinjection in this site; thus, the hyperresponsivity to mild auditory and visual stimuli and concurrent analgesia previously seen in animals with morphine microinjections in the periaqueductal gray matter appear to be dissociable effects of morphine, and site specific.", "contents": "Morphine-induced rotation in naive, nonlesioned rats. In rats injected with morphine in the midbrain reticular formation, pronounced ipsilateral rotation behavior was elicited by mild auditory and visual stimuli. The frequency of occurrence and rate of rotation were dose-dependent. This effect was site specific and drug specific; other drugs (except heroin) failed to induce this behavior. Naloxone potentiated the morphine rotation. Pretreatment with drugs that either potentiated or attenuated the morphine rotation indicated involvement of the noradrenergic and cholinergic systems and excluded a role for the dopaminergic system. No analgesia was observed after morphine microinjection in this site; thus, the hyperresponsivity to mild auditory and visual stimuli and concurrent analgesia previously seen in animals with morphine microinjections in the periaqueductal gray matter appear to be dissociable effects of morphine, and site specific."} {"id": "PMID:1257767", "title": "Falcon visual acuity.", "content": "Grating acuity, the ability to resolve high-contrast square-wave gratings, was measured in a falcon and in humans under comparable conditions. This behavioral test of falcon acuity supports the common belief that Falconiform\u00e8s have superb vision-the faclon's threshold was 160 cycles per degree, while the human thresholds were 60 cycles per degree. Falcon acuity, however, was much more dependent on lumanance, declining sharply with decreases in luminance.", "contents": "Falcon visual acuity. Grating acuity, the ability to resolve high-contrast square-wave gratings, was measured in a falcon and in humans under comparable conditions. This behavioral test of falcon acuity supports the common belief that Falconiform\u00e8s have superb vision-the faclon's threshold was 160 cycles per degree, while the human thresholds were 60 cycles per degree. Falcon acuity, however, was much more dependent on lumanance, declining sharply with decreases in luminance."} {"id": "PMID:1257770", "title": "Growth promotion by homocysteic acid.", "content": "Homocysteic acid, H03SCH2CH2CHNH2CO2H, promotes growth of hypophysectomized rats, assayed by observation of increased thickness of epiphyseal cartilage of the tibia and by observation of tail growth. Doses of homocysteic acid as low as 1 microgram per day for 4 days in the tibia assay and 2.5 milligrams per kilogram per day for 5 weeks in the tail assay were effective in promoting growth. Serum somatomedin activity, determined by the porcine cartilage disk assay, was also increased by homocysteic acid. These findings relate an area of sulfur amino acid metabolism to the physiological action of growth hormone, accelerated growth in homocystinuria, initiation of arteriosclerosis, and control of cellular growth.", "contents": "Growth promotion by homocysteic acid. Homocysteic acid, H03SCH2CH2CHNH2CO2H, promotes growth of hypophysectomized rats, assayed by observation of increased thickness of epiphyseal cartilage of the tibia and by observation of tail growth. Doses of homocysteic acid as low as 1 microgram per day for 4 days in the tibia assay and 2.5 milligrams per kilogram per day for 5 weeks in the tail assay were effective in promoting growth. Serum somatomedin activity, determined by the porcine cartilage disk assay, was also increased by homocysteic acid. These findings relate an area of sulfur amino acid metabolism to the physiological action of growth hormone, accelerated growth in homocystinuria, initiation of arteriosclerosis, and control of cellular growth."} {"id": "PMID:1257771", "title": "Peripheral blood elements found in an Egyptian mummy: a three-dimensional view.", "content": "Intact peripheral blood elements were found within an intracranial mass, possibly eithern an antemortem subdural hematoma or a postmortem blood clot, removed from a 2200-year-old Egyptian female mummy. Surface topographies of neutrophils and lymphocytes were similar. Some erythrocytes partially retained their biconcave disk shape; others were spherical. Individual platelets exhibited pseudopodia.", "contents": "Peripheral blood elements found in an Egyptian mummy: a three-dimensional view. Intact peripheral blood elements were found within an intracranial mass, possibly eithern an antemortem subdural hematoma or a postmortem blood clot, removed from a 2200-year-old Egyptian female mummy. Surface topographies of neutrophils and lymphocytes were similar. Some erythrocytes partially retained their biconcave disk shape; others were spherical. Individual platelets exhibited pseudopodia."} {"id": "PMID:1257772", "title": "Sexual differences in the auditory system of the tree frog Eleutherodactylus coqui.", "content": "Acoustic playback experiments with calling males in their natural habitat and two-choice orientation experiments with females indicate that males and females of the neotropical tree frog Elutherodactylus coqui respond to different notes in the two-note call of the male. This functional dichotomy of the two notes in the male's call reflects a difference in the distribution of the best excitatory frequencies of primary auditory neurons for the males and females. To the best of our knowledge, Eleutherodactylus is the first known example of a vertebrate in which the peripheral auditory sensitivity shows a sexual difference.", "contents": "Sexual differences in the auditory system of the tree frog Eleutherodactylus coqui. Acoustic playback experiments with calling males in their natural habitat and two-choice orientation experiments with females indicate that males and females of the neotropical tree frog Elutherodactylus coqui respond to different notes in the two-note call of the male. This functional dichotomy of the two notes in the male's call reflects a difference in the distribution of the best excitatory frequencies of primary auditory neurons for the males and females. To the best of our knowledge, Eleutherodactylus is the first known example of a vertebrate in which the peripheral auditory sensitivity shows a sexual difference."} {"id": "PMID:1257773", "title": "Incentive contrast in honey bees.", "content": "Bees trained to come to the laboratory for a 20% sucrose solution accept it readily, but bees trained with a 40% sucrose solution and tested with the 20% solution show a pattern of interrupted feeding that may last for several minutes. Bees trained with 20% and tested with 40% sucrose are undisturbed. When the animals are offered two samples of the 20% solution simultaneously, they drink to repletion from whichever they first taste on each visit, but if both a 20% and a 40% drop are offered the 20% solution is rejected after a single experience of the 40% solution. Although these results are analogous in many respects to incentive contrast effects found in mammals, they can be understood in sensory terms and do not require the assumption of learning about reward.", "contents": "Incentive contrast in honey bees. Bees trained to come to the laboratory for a 20% sucrose solution accept it readily, but bees trained with a 40% sucrose solution and tested with the 20% solution show a pattern of interrupted feeding that may last for several minutes. Bees trained with 20% and tested with 40% sucrose are undisturbed. When the animals are offered two samples of the 20% solution simultaneously, they drink to repletion from whichever they first taste on each visit, but if both a 20% and a 40% drop are offered the 20% solution is rejected after a single experience of the 40% solution. Although these results are analogous in many respects to incentive contrast effects found in mammals, they can be understood in sensory terms and do not require the assumption of learning about reward."} {"id": "PMID:1257774", "title": "Hyperphagia and increased growth in rats after intraventricular injection of 5,7-dihydroxytryptamine.", "content": "Juvenile male rats given intracerebroventricular injections of 5,7-dihydroxytryptamine, following treatment with desmethylimipramine, maintained body weight gains of 5 to 6 grams per day into adulthood and grew much larger than control rats. Biochemical analyses of brain tissue obtained 50 to 140 days after the injections revealed 60 to 86% depletions of telencephalic 5-hydroxytryptamine, with catecholamine levels unchanged. Hyperphagia did not develop despite comparable losses of 5-hydroxytryptamine when the pretreatment was withheld, perhaps because substantial depletions of norepinephrine occurred as well.", "contents": "Hyperphagia and increased growth in rats after intraventricular injection of 5,7-dihydroxytryptamine. Juvenile male rats given intracerebroventricular injections of 5,7-dihydroxytryptamine, following treatment with desmethylimipramine, maintained body weight gains of 5 to 6 grams per day into adulthood and grew much larger than control rats. Biochemical analyses of brain tissue obtained 50 to 140 days after the injections revealed 60 to 86% depletions of telencephalic 5-hydroxytryptamine, with catecholamine levels unchanged. Hyperphagia did not develop despite comparable losses of 5-hydroxytryptamine when the pretreatment was withheld, perhaps because substantial depletions of norepinephrine occurred as well."} {"id": "PMID:1257775", "title": "The \"pincushion grid\" illusion.", "content": "The illusion generated by a \"pincushion grid\" is not predicted from the two-dimensional Fourier transform of the grid. This implies that the visual system may not perform two-dimensional Fourier transforms of observed patterns.", "contents": "The \"pincushion grid\" illusion. The illusion generated by a \"pincushion grid\" is not predicted from the two-dimensional Fourier transform of the grid. This implies that the visual system may not perform two-dimensional Fourier transforms of observed patterns."} {"id": "PMID:1257776", "title": "Eyeblink inhibition by monaural and binaural stimulation: one ear is better than two.", "content": "Airpuff-elicited eyeblink, like many other reflexes, may be inhibited when an auditory stimulus precedes the reflex-eliciting stimulus by approximately 100 milliseconds. This inhibition is greater when the auditory stimulus is delivered to one ear than when it is presented binaurally.", "contents": "Eyeblink inhibition by monaural and binaural stimulation: one ear is better than two. Airpuff-elicited eyeblink, like many other reflexes, may be inhibited when an auditory stimulus precedes the reflex-eliciting stimulus by approximately 100 milliseconds. This inhibition is greater when the auditory stimulus is delivered to one ear than when it is presented binaurally."} {"id": "PMID:1257777", "title": "d-Amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striato-nigral feedback pathway.", "content": "Lesions of the striato-nigral pathways (that is, crus cerebri or vicinity of the tail of the caudate nucleus) markedly attenuate depressant effects of intravenous d-amphetamine on central dopaminergic cell activity. These results, coupled with previous data showing that microiontophoretic application of d-amphetamine directly onto dopaminergic cells does not produce significant slowing, provide direct support for the hypothesis that the depressant effect of d-amphetamine on these cells is mediated through a striato-nigral neuronal feedback loop.", "contents": "d-Amphetamine-induced inhibition of central dopaminergic neurons: mediation by a striato-nigral feedback pathway. Lesions of the striato-nigral pathways (that is, crus cerebri or vicinity of the tail of the caudate nucleus) markedly attenuate depressant effects of intravenous d-amphetamine on central dopaminergic cell activity. These results, coupled with previous data showing that microiontophoretic application of d-amphetamine directly onto dopaminergic cells does not produce significant slowing, provide direct support for the hypothesis that the depressant effect of d-amphetamine on these cells is mediated through a striato-nigral neuronal feedback loop."} {"id": "PMID:1257778", "title": "Stable and plastic unit discharge patterns during behavioral generalization.", "content": "A movable microelectrode was implanted in adult cats trained to respond differentially to two different frequencies of light flicker. Unit responses were recorded along cortical and thalamic trajectories. The late components of the poststimulus response of 29% of the cells examined showed statistically significant differences when data from different behavioral outcomes to the same neutral generalization stimulus were compared.", "contents": "Stable and plastic unit discharge patterns during behavioral generalization. A movable microelectrode was implanted in adult cats trained to respond differentially to two different frequencies of light flicker. Unit responses were recorded along cortical and thalamic trajectories. The late components of the poststimulus response of 29% of the cells examined showed statistically significant differences when data from different behavioral outcomes to the same neutral generalization stimulus were compared."} {"id": "PMID:1257780", "title": "Differing attenuation coefficients of normal and infarcted myocardium.", "content": "There are significant differences in attenuation coefficients between normal and infarcted myocardium measurable with a computerized transaxial tomographic scanner. Additionally, iodinated contrast material administered prior to killing the tests animals resulted in excellent visualization of the blood-myocardial interface at a time when standard radiographs detected no differences between the ventricular cavity and the myocardial wall. These natural and induced changes in attenuation coefficients offer a new approach to evaluating and understanding the processes of tissue injury and death. Their clinical relevance lies in application to the twin problems of myocardial infarction and the structure and function of the cardiac wall.", "contents": "Differing attenuation coefficients of normal and infarcted myocardium. There are significant differences in attenuation coefficients between normal and infarcted myocardium measurable with a computerized transaxial tomographic scanner. Additionally, iodinated contrast material administered prior to killing the tests animals resulted in excellent visualization of the blood-myocardial interface at a time when standard radiographs detected no differences between the ventricular cavity and the myocardial wall. These natural and induced changes in attenuation coefficients offer a new approach to evaluating and understanding the processes of tissue injury and death. Their clinical relevance lies in application to the twin problems of myocardial infarction and the structure and function of the cardiac wall."} {"id": "PMID:1257781", "title": "Phosphorylated sites in substrates of intracellular protein kinases: a common feature in amino acid sequences.", "content": "Examination of the primary amino acid sequences surrounding phosphorylated sites in many intracellular phosphoproteins indicated that the phosphorylated hydroxyamino acid (either serine or threonine) is, in general, surrounded by amino acids having a positively charged side chain and, more specifically, is frequently separated from a basic amino acid (either lysine or arginine) by only one amino acid. Possible reasons for this common feature are discussed.", "contents": "Phosphorylated sites in substrates of intracellular protein kinases: a common feature in amino acid sequences. Examination of the primary amino acid sequences surrounding phosphorylated sites in many intracellular phosphoproteins indicated that the phosphorylated hydroxyamino acid (either serine or threonine) is, in general, surrounded by amino acids having a positively charged side chain and, more specifically, is frequently separated from a basic amino acid (either lysine or arginine) by only one amino acid. Possible reasons for this common feature are discussed."} {"id": "PMID:1257782", "title": "Dendritic reorganization of an identified motoneuron during metamorphosis of the tobacco hornworm moth.", "content": "In the tobacco hornworm, many larval motoneurons become respecified and supply new muscles in the adult. Changes in the morphology of one such neuron were examined through metamorphosis. The dendritic pattern of the adult comes about both by outgrowth from the primary and secondary branches of the larval neuron and by the development of new branches that are unique to the adult.", "contents": "Dendritic reorganization of an identified motoneuron during metamorphosis of the tobacco hornworm moth. In the tobacco hornworm, many larval motoneurons become respecified and supply new muscles in the adult. Changes in the morphology of one such neuron were examined through metamorphosis. The dendritic pattern of the adult comes about both by outgrowth from the primary and secondary branches of the larval neuron and by the development of new branches that are unique to the adult."} {"id": "PMID:1257783", "title": "Neuronal substrate of classical conditioning in the hippocampus.", "content": "Neuronal activity in dorsal hippocampus was recorded in rabbits-during classical conditioning of nictitating membrane response, with tone as conditioned stimulus and corneal air puff as unconditioned stimulus. Unit activity in hippocampus rapidly forms a temporal neuronal \"model\" of the behavioral response early in training. This hippocampal response does not develop in control animals given unpaired stimuli.", "contents": "Neuronal substrate of classical conditioning in the hippocampus. Neuronal activity in dorsal hippocampus was recorded in rabbits-during classical conditioning of nictitating membrane response, with tone as conditioned stimulus and corneal air puff as unconditioned stimulus. Unit activity in hippocampus rapidly forms a temporal neuronal \"model\" of the behavioral response early in training. This hippocampal response does not develop in control animals given unpaired stimuli."} {"id": "PMID:1257784", "title": "Rapid discrimination of rewarding nutrient by the upper gastrointestinal tract.", "content": "When certain nutrients are injected into the stomachs of rats that are drinking one of two samples of nonnutrient, flavored water, the rats will (within a 10-minute session) choose the flavor paired with the nutrient. Such rewarding effects have obtained with predigested milk but not with similarly treated glucose or fresh milk. The results suggest the presence of rapidly acting, specialized, nutrient receptors in the upper gastrointestinal tract.", "contents": "Rapid discrimination of rewarding nutrient by the upper gastrointestinal tract. When certain nutrients are injected into the stomachs of rats that are drinking one of two samples of nonnutrient, flavored water, the rats will (within a 10-minute session) choose the flavor paired with the nutrient. Such rewarding effects have obtained with predigested milk but not with similarly treated glucose or fresh milk. The results suggest the presence of rapidly acting, specialized, nutrient receptors in the upper gastrointestinal tract."} {"id": "PMID:1257785", "title": "Lens culinaris lectin immobilized on sepharose: binding and sugar-specific release of intact tissue culture cells.", "content": "Lens culinaris lectin (LCL) covalently linked to 2B Sepharose binds tissue culture cells to the matrix. This is prevented by hapten sugars specific for LCL. Unlike other immobilized lectins, lens culinaris lectin allows the removal of bound cells from the matrix on addition of the specific sugars in a concentration-dependent manner. Binding and release occur under physiological conditions. Released cells continue to grow.", "contents": "Lens culinaris lectin immobilized on sepharose: binding and sugar-specific release of intact tissue culture cells. Lens culinaris lectin (LCL) covalently linked to 2B Sepharose binds tissue culture cells to the matrix. This is prevented by hapten sugars specific for LCL. Unlike other immobilized lectins, lens culinaris lectin allows the removal of bound cells from the matrix on addition of the specific sugars in a concentration-dependent manner. Binding and release occur under physiological conditions. Released cells continue to grow."} {"id": "PMID:1257786", "title": "Facial muscle patterning to affective imagery in depressed and nondepressed subjects.", "content": "When subjects imagine happy, sad, and angry situations, different patterns of facial muscle activity are produced which can be measured by electromyography. These subtle, typically covert, facial expression patterns differentiate depressed from nondepressed subjects. Facial electromyography can provide a sensitive, objective index of normal and clinical mood states.", "contents": "Facial muscle patterning to affective imagery in depressed and nondepressed subjects. When subjects imagine happy, sad, and angry situations, different patterns of facial muscle activity are produced which can be measured by electromyography. These subtle, typically covert, facial expression patterns differentiate depressed from nondepressed subjects. Facial electromyography can provide a sensitive, objective index of normal and clinical mood states."} {"id": "PMID:1257789", "title": "Evolution of genome size by DNA doublings.", "content": "Logarithmic distributions of nucleic acid contents per genome of species within major phylogenetic groups of organisms tend to form several peaks. These peaks appear to represent intragroup doublings of DNA or RNA which, in the case of eukaryotes, are independent of polyploidy. This phenomenon has been termed cryptopolyploidy. There are numerical similarities in peak values for different taxonomic groups. A high degree of order is suggested when minimum values for the major phylogenetic groups are plotted against a series of theoretical doublings. These data demonstrate the apparent existence of an exponential periodicity over eight orders of magnitude, leading us to suggest an evolutionary continuity of doublings of a basic ancestral genome (of about 300 nucleotides), these doublings being independent of both chromosome number and ploidy level. This proposed continuity encompasses most major life forms and is generally concomitant with increasing evolutionary complexity, particularly in the prokaryotes and lower eukaryotes. Our interpretation of the data presented here must currently be viewed as speculative, and we do not propose that genome doubling is the only mechanism for genome evolution. However, we feel that the evidence is sufficient to warrant serious scrutiny of our proposals. We hope that this approach to a synthesis of available data will provoke discussion and will stimulate further work toward either supporting, modifying, or disproving our hypothesis.", "contents": "Evolution of genome size by DNA doublings. Logarithmic distributions of nucleic acid contents per genome of species within major phylogenetic groups of organisms tend to form several peaks. These peaks appear to represent intragroup doublings of DNA or RNA which, in the case of eukaryotes, are independent of polyploidy. This phenomenon has been termed cryptopolyploidy. There are numerical similarities in peak values for different taxonomic groups. A high degree of order is suggested when minimum values for the major phylogenetic groups are plotted against a series of theoretical doublings. These data demonstrate the apparent existence of an exponential periodicity over eight orders of magnitude, leading us to suggest an evolutionary continuity of doublings of a basic ancestral genome (of about 300 nucleotides), these doublings being independent of both chromosome number and ploidy level. This proposed continuity encompasses most major life forms and is generally concomitant with increasing evolutionary complexity, particularly in the prokaryotes and lower eukaryotes. Our interpretation of the data presented here must currently be viewed as speculative, and we do not propose that genome doubling is the only mechanism for genome evolution. However, we feel that the evidence is sufficient to warrant serious scrutiny of our proposals. We hope that this approach to a synthesis of available data will provoke discussion and will stimulate further work toward either supporting, modifying, or disproving our hypothesis."} {"id": "PMID:1257791", "title": "Binocular vision: two possible central interactions between signals from two eyes.", "content": "Both foveae of light-adapted subjects were stimulated at the same time with monocularly presented lights of increasing or decreasing luminance. Combinations judged just detectable violated predictions of the energy summation and the probability summation hypotheses of binocular interaction. Rather, the results can be explained by independent central neural mechanisms that signal the sum or the difference of stimuli to two eyes.", "contents": "Binocular vision: two possible central interactions between signals from two eyes. Both foveae of light-adapted subjects were stimulated at the same time with monocularly presented lights of increasing or decreasing luminance. Combinations judged just detectable violated predictions of the energy summation and the probability summation hypotheses of binocular interaction. Rather, the results can be explained by independent central neural mechanisms that signal the sum or the difference of stimuli to two eyes."} {"id": "PMID:1257792", "title": "Complement-dependent immunoglobulin G receptor function in lymphoid cells.", "content": "Lymphoid cells are unable to lyse antibody-coated target cells in the presence of normal immunoglobulin G (IgG), presumably because their surface receptors of IgG are blocked. However, when target cells are sensitized with antibodies and complement, IgG receptors are unblocked and cytotoxicity occurs even in the presence of normal IgG. Thus, IgG receptors may function in vivo despite the relatively high concentations of IgG in serum and interstitial fluid.", "contents": "Complement-dependent immunoglobulin G receptor function in lymphoid cells. Lymphoid cells are unable to lyse antibody-coated target cells in the presence of normal immunoglobulin G (IgG), presumably because their surface receptors of IgG are blocked. However, when target cells are sensitized with antibodies and complement, IgG receptors are unblocked and cytotoxicity occurs even in the presence of normal IgG. Thus, IgG receptors may function in vivo despite the relatively high concentations of IgG in serum and interstitial fluid."} {"id": "PMID:1257793", "title": "Antiserum to somatostatin prevents stress-induced inhibition of growth hormone secretion in the rat.", "content": "Plasma growth hormone levels fall and remain low for several hours after stress in the rat. When antiserums to somatostatin are administered to rats prior to stress, growth hormone secretory pulses are partially restored. The results provide evidence that circulating somatostatin plays a prominent role in stress-induced inhibition of growth hormone secretion in the rat.", "contents": "Antiserum to somatostatin prevents stress-induced inhibition of growth hormone secretion in the rat. Plasma growth hormone levels fall and remain low for several hours after stress in the rat. When antiserums to somatostatin are administered to rats prior to stress, growth hormone secretory pulses are partially restored. The results provide evidence that circulating somatostatin plays a prominent role in stress-induced inhibition of growth hormone secretion in the rat."} {"id": "PMID:1257794", "title": "Sibling species in the marine pollution indicator Capitella (polychaeta).", "content": "Electrophoretic patterns for eight enzyme loci clearly distinguish six sibling species in the well-known pollution indicator worm, Capitella capitata. Unlike sibling species of Drosophila, the Capitella species have virtually no alleles in common. Close examination has revealed only slight morphological differences between species, while life histories and reproductive modes are very distinct. The Capitella species are ideally suited for genetic and evolutionary studies.", "contents": "Sibling species in the marine pollution indicator Capitella (polychaeta). Electrophoretic patterns for eight enzyme loci clearly distinguish six sibling species in the well-known pollution indicator worm, Capitella capitata. Unlike sibling species of Drosophila, the Capitella species have virtually no alleles in common. Close examination has revealed only slight morphological differences between species, while life histories and reproductive modes are very distinct. The Capitella species are ideally suited for genetic and evolutionary studies."} {"id": "PMID:1257795", "title": "Sex differences in cognition: a function of maturation rate?", "content": "Regardless of sex, early maturing adolescents performed better on tests of verbal than spatial abilities, the late maturing ones showed the opposite pattern. Those maturing late were more lateralized for speech than those maturing early. Sex differences in mental abilities, it is argued, reflect differences in the organization of cortical function that are related to differential rates of physical maturation.", "contents": "Sex differences in cognition: a function of maturation rate? Regardless of sex, early maturing adolescents performed better on tests of verbal than spatial abilities, the late maturing ones showed the opposite pattern. Those maturing late were more lateralized for speech than those maturing early. Sex differences in mental abilities, it is argued, reflect differences in the organization of cortical function that are related to differential rates of physical maturation."} {"id": "PMID:1257815", "title": "Management of breast cancer: past, present, future.", "content": "The historical management of breast cancer leading up to the Halsted era is reviewed. Radical mastectomy is examined and evaluated in the light of cancer staging, and different modes of treatment are discussed. The question of what type of surgery and adjuvant therapy is best for each patient is not fully answered and awaits further study and clinical trials. The future promises an immunobiologic approach in the treatment of breast cancer in addition to early operation.", "contents": "Management of breast cancer: past, present, future. The historical management of breast cancer leading up to the Halsted era is reviewed. Radical mastectomy is examined and evaluated in the light of cancer staging, and different modes of treatment are discussed. The question of what type of surgery and adjuvant therapy is best for each patient is not fully answered and awaits further study and clinical trials. The future promises an immunobiologic approach in the treatment of breast cancer in addition to early operation."} {"id": "PMID:1257816", "title": "The breast cancer conundrum.", "content": "The rate of survival for patients with breast cancer is determined by the interaction of the tumor spread and the tissue ablated by the method. Clinical estimates of tumor spread are grossly inaccurate. Therefore the rate of survival is an unreliable index of the quality of the method, and a comparison of survival rates is not likely to reveal which method is superior. Nevertheless, the cancer arises in the breast, spreads away from the breast, cannot be accurately staged, and must be totally eradicated for the achievement of cure. The principle of treatment is therefore the ablation of the primary tumor and the largest amount of adjacent expendable tissue at the earliest time. Compliance of the method with this principle will produce the best possible result. Superior therapy is evidenced by compliance of the method with the principle of treatment rather than by a comparison of the rates of survival.", "contents": "The breast cancer conundrum. The rate of survival for patients with breast cancer is determined by the interaction of the tumor spread and the tissue ablated by the method. Clinical estimates of tumor spread are grossly inaccurate. Therefore the rate of survival is an unreliable index of the quality of the method, and a comparison of survival rates is not likely to reveal which method is superior. Nevertheless, the cancer arises in the breast, spreads away from the breast, cannot be accurately staged, and must be totally eradicated for the achievement of cure. The principle of treatment is therefore the ablation of the primary tumor and the largest amount of adjacent expendable tissue at the earliest time. Compliance of the method with this principle will produce the best possible result. Superior therapy is evidenced by compliance of the method with the principle of treatment rather than by a comparison of the rates of survival."} {"id": "PMID:1257817", "title": "Cholesterol crystal microembolization: a cause of the restless leg syndrome.", "content": "The restless leg syndrome is characterized by unpleasant lower extremity nocturnal aching, muscle cramps, and restless shuffling. Although the cause remains unknown in the majority of cases, two instances are reported of the restless leg syndrome caused by peripheral cholesterol crystal microemboli. The syndrome caused by cholesterol microemboli and the syndromes of the restless leg are reviewed.", "contents": "Cholesterol crystal microembolization: a cause of the restless leg syndrome. The restless leg syndrome is characterized by unpleasant lower extremity nocturnal aching, muscle cramps, and restless shuffling. Although the cause remains unknown in the majority of cases, two instances are reported of the restless leg syndrome caused by peripheral cholesterol crystal microemboli. The syndrome caused by cholesterol microemboli and the syndromes of the restless leg are reviewed."} {"id": "PMID:1257818", "title": "Retrospective critical review and analysis of bilateral staged pulmonary resections for treatment of pulmonary tuberculosis.", "content": "A critical retrospective analysis of 14 cases of bilateral staged pulmonary resections for the treatment of pulmonary tuberculosis is described. Lobectomies with or without segmentectomies were the preferred procedures. The four positive cases had mostly cavitary disease (85%) with positive bacteriologic culture from the specimens (75%). The ten negative cases had less cavitary disease (65%) with negative bacteriologic culture of the specimens (90%). Positive residual bacteriologic specimen activity (10%) of the negative group favors the surgical removal of residual disease, despite the fact that 45% have no culture or bacterial stain obtained. Negative residual bacteriologic specimen activity (25%) of the positive group indicates the limitations of inadequate surgery. Thus the indications of surgery may gradually reestablish their own crieteria in this era of massive chemotherapy.", "contents": "Retrospective critical review and analysis of bilateral staged pulmonary resections for treatment of pulmonary tuberculosis. A critical retrospective analysis of 14 cases of bilateral staged pulmonary resections for the treatment of pulmonary tuberculosis is described. Lobectomies with or without segmentectomies were the preferred procedures. The four positive cases had mostly cavitary disease (85%) with positive bacteriologic culture from the specimens (75%). The ten negative cases had less cavitary disease (65%) with negative bacteriologic culture of the specimens (90%). Positive residual bacteriologic specimen activity (10%) of the negative group favors the surgical removal of residual disease, despite the fact that 45% have no culture or bacterial stain obtained. Negative residual bacteriologic specimen activity (25%) of the positive group indicates the limitations of inadequate surgery. Thus the indications of surgery may gradually reestablish their own crieteria in this era of massive chemotherapy."} {"id": "PMID:1257819", "title": "An analysis of practice in Georgia and South Dakota.", "content": "Family practitioners in Georgia and South Dakota were surveyed in order to ascertain percentage of practice devoted to various specialty areas, daily case loads, type of diagnoses, method of handling telephone calls, and patterns of agency utilization. Questionnaires were sent to all South Dakota and Georgia family practitioners. In Georgia 22% of family practitioners do no surgery and 55% do no obstetrics, while in South Dakota 90% practice obstetrics. Differences in availability of specialists and in pysician referral patterns caused marked variations in family practice patterns. Diagnoses showing geographic differences included chronic lung disease, arthritis, sore throat, heart disease, and neuroses. About 50% of all physicians handled medical phone calls personally. Less than half the respondents in each state used some agency or resource in this time period. The distribution of specialists affects the patient load and needs to be considered when primary care is planned.", "contents": "An analysis of practice in Georgia and South Dakota. Family practitioners in Georgia and South Dakota were surveyed in order to ascertain percentage of practice devoted to various specialty areas, daily case loads, type of diagnoses, method of handling telephone calls, and patterns of agency utilization. Questionnaires were sent to all South Dakota and Georgia family practitioners. In Georgia 22% of family practitioners do no surgery and 55% do no obstetrics, while in South Dakota 90% practice obstetrics. Differences in availability of specialists and in pysician referral patterns caused marked variations in family practice patterns. Diagnoses showing geographic differences included chronic lung disease, arthritis, sore throat, heart disease, and neuroses. About 50% of all physicians handled medical phone calls personally. Less than half the respondents in each state used some agency or resource in this time period. The distribution of specialists affects the patient load and needs to be considered when primary care is planned."} {"id": "PMID:1257821", "title": "Alveolar soft part sarcoma.", "content": "Alveolar soft part sarcoma is a rare, highly malignant tumor. It usually arises in the skeletal muscles in the extremities of patients in their second or third decade with a female preponderance of 2:1. Three additional cases, including the angiographic findings, have been presented. The literature pertaining to this subject also has been reviewed.", "contents": "Alveolar soft part sarcoma. Alveolar soft part sarcoma is a rare, highly malignant tumor. It usually arises in the skeletal muscles in the extremities of patients in their second or third decade with a female preponderance of 2:1. Three additional cases, including the angiographic findings, have been presented. The literature pertaining to this subject also has been reviewed."} {"id": "PMID:1257823", "title": "Blood trace metals in military recruits.", "content": "Whole blood samples obtained from 2,000 military recruits were analyzed for cadmium, copper, lead, and zinc by atomic absorption spectroscopy. Whole blood copper levels were symmetrically distributed and those for cadmium, lead, and zinc were positively skewed. Average whole blood levels for copper and zinc were generally comparable to published values, but cadmium and lead values were somewhat higher, suggesting possible absorption of trace metals from containers during storage. Average cadmium and zinc levels were similar among blacks and whites, whereas average copper and lead levels were significantly higher in blacks. Cigarette smokers had higher copper levels than nonsmokers. Cadmium and zinc whole blood levels varied inversely with educational attainment. Copper, lead, and zinc levels varied by place of residence, suggesting the influence of dietary or other factors. Future studies characterizing trace metal body burdens or relating trace metals to diseases must carefully measure such pertinent attributes as age, sex, race or ethnic group, smoking habits, diet, and environmental exposure.", "contents": "Blood trace metals in military recruits. Whole blood samples obtained from 2,000 military recruits were analyzed for cadmium, copper, lead, and zinc by atomic absorption spectroscopy. Whole blood copper levels were symmetrically distributed and those for cadmium, lead, and zinc were positively skewed. Average whole blood levels for copper and zinc were generally comparable to published values, but cadmium and lead values were somewhat higher, suggesting possible absorption of trace metals from containers during storage. Average cadmium and zinc levels were similar among blacks and whites, whereas average copper and lead levels were significantly higher in blacks. Cigarette smokers had higher copper levels than nonsmokers. Cadmium and zinc whole blood levels varied inversely with educational attainment. Copper, lead, and zinc levels varied by place of residence, suggesting the influence of dietary or other factors. Future studies characterizing trace metal body burdens or relating trace metals to diseases must carefully measure such pertinent attributes as age, sex, race or ethnic group, smoking habits, diet, and environmental exposure."} {"id": "PMID:1257824", "title": "Isoniazid-induced convulsions.", "content": "Acute isoniazid overdose and toxicity may be complicated by convulsions and death. Six patients are reported, one of whom ingested simultaneously 15 gm of isoniazid and 5 gm of pyridoxine hydrochloride (vitamin B6); no convulsions resulted. In the light of this and other experience, suggestions are made for the use of pyridoxine in the treatment and prevention of acute isoniazid poisoning.", "contents": "Isoniazid-induced convulsions. Acute isoniazid overdose and toxicity may be complicated by convulsions and death. Six patients are reported, one of whom ingested simultaneously 15 gm of isoniazid and 5 gm of pyridoxine hydrochloride (vitamin B6); no convulsions resulted. In the light of this and other experience, suggestions are made for the use of pyridoxine in the treatment and prevention of acute isoniazid poisoning."} {"id": "PMID:1257825", "title": "Multiple myeloma in Oklahoma: racial, age, sex, geographic and time variations.", "content": "Oklahoma death certificates listing multiple myeloma as the underlying cause of death during the period 1950-1970 were examined for secular trends, and geographic and demographic characteristics associated with the disease. An upward trend in the death rates for all age, sex and race groups was found; the most dramatic increases were seen in the oldest age groups. During the 20-year period, the death rate for white males 75 years of age and older increased tenfold. For white females 75 years of age and older. It increased eightfold. White male rates were constantly higher and showed a sharper increase in age-adjusted death rates than white female rates. Because of the low number of nonwhite deaths in Oklahoma from multiple myeloma, the rates showed extreme fluctuations. After adjustments were made for age differences, the nonwhite annual rate was 2.36 per 100,000 compared with 1.62 for the white population. There was not enough information to draw conclusions about the geographic distribution of multiple myeloma. Findings for the Oklahoma population were consistent with the few previously reported studies.", "contents": "Multiple myeloma in Oklahoma: racial, age, sex, geographic and time variations. Oklahoma death certificates listing multiple myeloma as the underlying cause of death during the period 1950-1970 were examined for secular trends, and geographic and demographic characteristics associated with the disease. An upward trend in the death rates for all age, sex and race groups was found; the most dramatic increases were seen in the oldest age groups. During the 20-year period, the death rate for white males 75 years of age and older increased tenfold. For white females 75 years of age and older. It increased eightfold. White male rates were constantly higher and showed a sharper increase in age-adjusted death rates than white female rates. Because of the low number of nonwhite deaths in Oklahoma from multiple myeloma, the rates showed extreme fluctuations. After adjustments were made for age differences, the nonwhite annual rate was 2.36 per 100,000 compared with 1.62 for the white population. There was not enough information to draw conclusions about the geographic distribution of multiple myeloma. Findings for the Oklahoma population were consistent with the few previously reported studies."} {"id": "PMID:1257826", "title": "A new instrument for uncomplicated emergency cricothyrotomy.", "content": "A new device for establishing an emergency airway provides sterility, anesthesia, control of bleeding, safe and quick entrance into the cricothyroid space, and adequate air exchange. In addition, the device is compatible with standard anesthetic and resuscitation machines, inexpensive, and small enough to be carried in a pocket.", "contents": "A new instrument for uncomplicated emergency cricothyrotomy. A new device for establishing an emergency airway provides sterility, anesthesia, control of bleeding, safe and quick entrance into the cricothyroid space, and adequate air exchange. In addition, the device is compatible with standard anesthetic and resuscitation machines, inexpensive, and small enough to be carried in a pocket."} {"id": "PMID:1257827", "title": "Sudden unexplained death in a psychiatric patient taking thioridazine.", "content": "This report describes the sudden unexplained death of a young, physically healthy, psychotic woman. She had received moderate doses of thioridazine for four days prior to her death. No cause of death could be determined at autopsy. The literature regarding other such case reports and possible cardiotoxic effects of phenothiazine is cited, but no clear-cut correlations or explanations have been demonstrated.", "contents": "Sudden unexplained death in a psychiatric patient taking thioridazine. This report describes the sudden unexplained death of a young, physically healthy, psychotic woman. She had received moderate doses of thioridazine for four days prior to her death. No cause of death could be determined at autopsy. The literature regarding other such case reports and possible cardiotoxic effects of phenothiazine is cited, but no clear-cut correlations or explanations have been demonstrated."} {"id": "PMID:1257828", "title": "Epidemiologic aspects of nosocomial infections.", "content": "In a currently ongoing surveillance of hospital-associated infections in two metropolitan hospitals in Oklahoma, the results over a four-month period suggest at least tentative principles of host-agent relationships in hospital-associated infections. Within the urinary tract, the site with the highest number of total isolations, Escherichia coli and Klebsiella pneumoniae were the most common pathogens. By age, the under 5 and over 60 year age groups had the highest number of isolations. Staphylococcus aureus and E coli were isolated more frequently in the younger group, while K pneumoniae, Serratia marcescens, and Proteus mirabilis occurred more frequently in infections among the older group. A higher frequency of Enterobacter sp and S aureus were isolated among male patients, while Candida albicans and E coli apparently had a greater affinity for females; however, none of these differences by sex were statistically significant. Over 50% of the infections were manifest within the first ten days of hospitalization.", "contents": "Epidemiologic aspects of nosocomial infections. In a currently ongoing surveillance of hospital-associated infections in two metropolitan hospitals in Oklahoma, the results over a four-month period suggest at least tentative principles of host-agent relationships in hospital-associated infections. Within the urinary tract, the site with the highest number of total isolations, Escherichia coli and Klebsiella pneumoniae were the most common pathogens. By age, the under 5 and over 60 year age groups had the highest number of isolations. Staphylococcus aureus and E coli were isolated more frequently in the younger group, while K pneumoniae, Serratia marcescens, and Proteus mirabilis occurred more frequently in infections among the older group. A higher frequency of Enterobacter sp and S aureus were isolated among male patients, while Candida albicans and E coli apparently had a greater affinity for females; however, none of these differences by sex were statistically significant. Over 50% of the infections were manifest within the first ten days of hospitalization."} {"id": "PMID:1257829", "title": "Cast bracing for femoral shaft fractures.", "content": "The femoral cast-brace offers a new method of treatment for femoral shaft fractures. The cast-brace is especially well suited to fractures below the isthmus, although it can be used to treat those more proximal by giving special attention to detail. The method allows early knee motion without prolonged bed rest. Patients who should not be operated on for any medical reason or whose fracture is not amenable to surgery may be treated with the cast-brace. A series of patients with simple and complicated problems that have been treated with the cast-brace is presented. Comparisons between femoral cast-bracing, intramedullary nailing, and traction treatment are made.", "contents": "Cast bracing for femoral shaft fractures. The femoral cast-brace offers a new method of treatment for femoral shaft fractures. The cast-brace is especially well suited to fractures below the isthmus, although it can be used to treat those more proximal by giving special attention to detail. The method allows early knee motion without prolonged bed rest. Patients who should not be operated on for any medical reason or whose fracture is not amenable to surgery may be treated with the cast-brace. A series of patients with simple and complicated problems that have been treated with the cast-brace is presented. Comparisons between femoral cast-bracing, intramedullary nailing, and traction treatment are made."} {"id": "PMID:1257830", "title": "Barrett's esophagus: a multifaceted condition.", "content": "Five patients with Barrett's esophagus, each with a differing presentation, serve as the basis of this report. Hiatal hernia is noted to be frequently present in Barrett's esophagus, and the incidence of adenocarcinoma is thought to be distinctly increased. The condition is easily diagnosed by fiberoptic endoscopy and verified by direct biopsy. The increasing use of fiberoptic panendoscopy may lead to an increased frequency of diagnosis of the columnar cell-lined lower esophagus and its complications.", "contents": "Barrett's esophagus: a multifaceted condition. Five patients with Barrett's esophagus, each with a differing presentation, serve as the basis of this report. Hiatal hernia is noted to be frequently present in Barrett's esophagus, and the incidence of adenocarcinoma is thought to be distinctly increased. The condition is easily diagnosed by fiberoptic endoscopy and verified by direct biopsy. The increasing use of fiberoptic panendoscopy may lead to an increased frequency of diagnosis of the columnar cell-lined lower esophagus and its complications."} {"id": "PMID:1257831", "title": "Staphylococcal septicemia: successful treatment of complications in a child.", "content": "A previously healthy 5-year-old girl developed staphylococcal septicemia. Initially, cardiovascular failure with mitral insufficiency and purulent pericarditis dominated the clinical picture. Peripheral thromboembolic phenomena, meningitis, osteomyelitis, and persistent septicemia were subsequently encountered during antimicrobial and surgical therapy. Although staphylococcal septicemia is a potentially lethal disorder, anticipation of its natural course and its possible complications should lead to more successful management.", "contents": "Staphylococcal septicemia: successful treatment of complications in a child. A previously healthy 5-year-old girl developed staphylococcal septicemia. Initially, cardiovascular failure with mitral insufficiency and purulent pericarditis dominated the clinical picture. Peripheral thromboembolic phenomena, meningitis, osteomyelitis, and persistent septicemia were subsequently encountered during antimicrobial and surgical therapy. Although staphylococcal septicemia is a potentially lethal disorder, anticipation of its natural course and its possible complications should lead to more successful management."} {"id": "PMID:1257832", "title": "Arteriomesenteric duodenal compression syndrome: comparison of methods of treatment.", "content": "A group of 80 patients with arteriomesenteric duodenal compression syndrome was reviewed, 48 from the general population and 32 from the Hines, Illinois, VA Hospital. Differences in the patient populations are pointed out, as are differences in the therapeutic results. An additional series is reported. Duodenojejunostomy is a safe and effective operation for the majority of patients who require surgery for this condition, and patients are less likely to require further medical or surgical care than those who have section of the ligament of Treitz.", "contents": "Arteriomesenteric duodenal compression syndrome: comparison of methods of treatment. A group of 80 patients with arteriomesenteric duodenal compression syndrome was reviewed, 48 from the general population and 32 from the Hines, Illinois, VA Hospital. Differences in the patient populations are pointed out, as are differences in the therapeutic results. An additional series is reported. Duodenojejunostomy is a safe and effective operation for the majority of patients who require surgery for this condition, and patients are less likely to require further medical or surgical care than those who have section of the ligament of Treitz."} {"id": "PMID:1257834", "title": "Clindamycin-associated pseudomembranous colitis treated with prednisone.", "content": "A patient with clindamycin-associated pseudomembranous colitis is presented. His dramatic response to prednisone suggested an immunologic basis of the disease process. This aspect of etiology and therapy has not been emphasized previously. Similar patients with clindamycin-associated pseudomembranous colitis should be sought out and consideration should be given to this type of treatment.", "contents": "Clindamycin-associated pseudomembranous colitis treated with prednisone. A patient with clindamycin-associated pseudomembranous colitis is presented. His dramatic response to prednisone suggested an immunologic basis of the disease process. This aspect of etiology and therapy has not been emphasized previously. Similar patients with clindamycin-associated pseudomembranous colitis should be sought out and consideration should be given to this type of treatment."} {"id": "PMID:1257835", "title": "The unexpected pheochromocytoma.", "content": "We have presented the case history of a patient with unilateral pyelonephritis and elevated peripheral venous renin, an obvious cause of renal hypertension. However, a complete evaluation revealed pheochromocytoma as the primary cause of the hypertension. It is assumed that the increase in renin is secondary to catecholamine stimulation. Since surgery or diagnostic procedures may be disastrous in a patient with unsuspected pheochromocytoma, we urge all physicians to make a special effort to detect the presence of a tumor in the hypertensive patient.", "contents": "The unexpected pheochromocytoma. We have presented the case history of a patient with unilateral pyelonephritis and elevated peripheral venous renin, an obvious cause of renal hypertension. However, a complete evaluation revealed pheochromocytoma as the primary cause of the hypertension. It is assumed that the increase in renin is secondary to catecholamine stimulation. Since surgery or diagnostic procedures may be disastrous in a patient with unsuspected pheochromocytoma, we urge all physicians to make a special effort to detect the presence of a tumor in the hypertensive patient."} {"id": "PMID:1257836", "title": "Liver hernia diagnosed by liver scan and confirmed by angiography.", "content": "A right-sided diaphragmatic hernia contining a portion of liver is presented. The diagnosis was made by liver scan and confirmed by selective angiography. The clinical and radiologic findings are discussed. The arteriogram of the herniated liver is the first angiographic demonstration of this entity.", "contents": "Liver hernia diagnosed by liver scan and confirmed by angiography. A right-sided diaphragmatic hernia contining a portion of liver is presented. The diagnosis was made by liver scan and confirmed by selective angiography. The clinical and radiologic findings are discussed. The arteriogram of the herniated liver is the first angiographic demonstration of this entity."} {"id": "PMID:1257852", "title": "Pharmacological prophylaxis of venous thrombo-embolism.", "content": "The pathogenesis of venous thrombosis is briefly discussed as a basis for the understanding of preventive measures used in this condition. Prophylaxis in venous thrombosis is then reviewed with emphasis on pharmacological treatment, and more particularly on heparin.", "contents": "Pharmacological prophylaxis of venous thrombo-embolism. The pathogenesis of venous thrombosis is briefly discussed as a basis for the understanding of preventive measures used in this condition. Prophylaxis in venous thrombosis is then reviewed with emphasis on pharmacological treatment, and more particularly on heparin."} {"id": "PMID:1257853", "title": "Portal vein thrombosis with ascites. A case report.", "content": "A case of portal vein thrombosis with ascites in an adult is presented with postmortem findings. The experience at Groote Schuur Hospital of portal vein thrombosis and Budd-Chiari syndrome between 1964 and 1974 is summarised and the literature is reviewed.", "contents": "Portal vein thrombosis with ascites. A case report. A case of portal vein thrombosis with ascites in an adult is presented with postmortem findings. The experience at Groote Schuur Hospital of portal vein thrombosis and Budd-Chiari syndrome between 1964 and 1974 is summarised and the literature is reviewed."} {"id": "PMID:1257854", "title": "A full-term fetus with holo-acranial anencephaly and other abnormalities.", "content": "A fetus with no head or neck was dissected in order to trace possible remnants of those structures. Many other abnormalities were also displayed. Mechanisms of anencephaly are discussed, especially those which probably caused this malformation.", "contents": "A full-term fetus with holo-acranial anencephaly and other abnormalities. A fetus with no head or neck was dissected in order to trace possible remnants of those structures. Many other abnormalities were also displayed. Mechanisms of anencephaly are discussed, especially those which probably caused this malformation."} {"id": "PMID:1257855", "title": "Polyostotic fibrous dysplasia with acromegaly (Albright's syndrome). A case report.", "content": "The association of polyostotic fibrous dysplasia and acromegaly, presenting with gross deformity of the skull and fractures of the left femur and right humerus, is described in a 42-year-old Black woman. Possible causative factors are discussed.", "contents": "Polyostotic fibrous dysplasia with acromegaly (Albright's syndrome). A case report. The association of polyostotic fibrous dysplasia and acromegaly, presenting with gross deformity of the skull and fractures of the left femur and right humerus, is described in a 42-year-old Black woman. Possible causative factors are discussed."} {"id": "PMID:1257857", "title": "The blocking by autologous serum of maternal cell-mediated immune reactions to placental antigen.", "content": "The reactivity of splenic lymphocytes to a placental antigen was assessed in pregnant and control rats by means of a macrophage migration inhibition test. The pregnant but not the control animals, showed increasing cell-mediated immunity, which persisted until the second week after parturition. Migration inhibition could be abolished when sensitised lymphocytes were first pulsed with serum from the pregnant animal in the presence of antigen. This blocking effect was obtained only with autologous but not with normal or heterologous pregnant rat serum, and did not occur when antigen was omitted from the pulse. The results indicate that pregnant animals have cell-mediated immunity against a placental antigen, but the serum of these animals has a central enhancing effect which is antigen-dependent.", "contents": "The blocking by autologous serum of maternal cell-mediated immune reactions to placental antigen. The reactivity of splenic lymphocytes to a placental antigen was assessed in pregnant and control rats by means of a macrophage migration inhibition test. The pregnant but not the control animals, showed increasing cell-mediated immunity, which persisted until the second week after parturition. Migration inhibition could be abolished when sensitised lymphocytes were first pulsed with serum from the pregnant animal in the presence of antigen. This blocking effect was obtained only with autologous but not with normal or heterologous pregnant rat serum, and did not occur when antigen was omitted from the pulse. The results indicate that pregnant animals have cell-mediated immunity against a placental antigen, but the serum of these animals has a central enhancing effect which is antigen-dependent."} {"id": "PMID:1257858", "title": "Aspects of radiofolate absorption, metabolism and plasma binding.", "content": "After 14C-methyl folate (14C-MeTHF) was taken by mouth, progressive incorporation of this istope into the dialysis-resistant plasma folate fraction occurred. At 6 hours 68,9% of the total plasma radioactive folate was dialysis-resistant. We have previously shown that 14C-folic acid (14C-PGA) taken by mouth is not similarly bound at 6 hours. Chromatography of plasma on DEA A50 after 14C-PGA absorption, showed that PGA in plasma (peak 1) was gradually converted to MeTHF (peak 2) and the absence of bound radiofolate 6 hours after 14C-PGA ingestion probably reflects this conversion phase. No radiofolate appeared in red cells up to 11 days after isotope ingestion. Initial divergence between plasma biofolate and radiofolate indicated that 'cold' storage folate was being displaced by abosrbed radiofolate. Urinary radiofolate resolved into 3 fractions (peaks 2, 3 and4) on DEAE A50 chromatography. One of these (peak 2) corresponded to MeTHF, but PGA (peak 1) was absent. Plasma showed peaks 1, 2 and 3, but at 3 hours no equivalent of urinary peak 4 was evident. Further studies are indicated to characterise fractions 3 and 4.", "contents": "Aspects of radiofolate absorption, metabolism and plasma binding. After 14C-methyl folate (14C-MeTHF) was taken by mouth, progressive incorporation of this istope into the dialysis-resistant plasma folate fraction occurred. At 6 hours 68,9% of the total plasma radioactive folate was dialysis-resistant. We have previously shown that 14C-folic acid (14C-PGA) taken by mouth is not similarly bound at 6 hours. Chromatography of plasma on DEA A50 after 14C-PGA absorption, showed that PGA in plasma (peak 1) was gradually converted to MeTHF (peak 2) and the absence of bound radiofolate 6 hours after 14C-PGA ingestion probably reflects this conversion phase. No radiofolate appeared in red cells up to 11 days after isotope ingestion. Initial divergence between plasma biofolate and radiofolate indicated that 'cold' storage folate was being displaced by abosrbed radiofolate. Urinary radiofolate resolved into 3 fractions (peaks 2, 3 and4) on DEAE A50 chromatography. One of these (peak 2) corresponded to MeTHF, but PGA (peak 1) was absent. Plasma showed peaks 1, 2 and 3, but at 3 hours no equivalent of urinary peak 4 was evident. Further studies are indicated to characterise fractions 3 and 4."} {"id": "PMID:1257863", "title": "Some clinical problems in patients undergoing thrombolytic therapy.", "content": "A total of 25 patients (7 with arterial occlusion and 18 with venous thrombosis) were treated with streptokinase for 72 hours, followed by heparin for 24 hours. The clinical problems, complications and results obtained are discussed. Within the limits imposed by the study, it is concluded that streptokinase offers safe and effective therapy for early iliofemoral venous thrombosis.", "contents": "Some clinical problems in patients undergoing thrombolytic therapy. A total of 25 patients (7 with arterial occlusion and 18 with venous thrombosis) were treated with streptokinase for 72 hours, followed by heparin for 24 hours. The clinical problems, complications and results obtained are discussed. Within the limits imposed by the study, it is concluded that streptokinase offers safe and effective therapy for early iliofemoral venous thrombosis."} {"id": "PMID:1257864", "title": "The need for objective diagnosis of deep vein thrombosis.", "content": "In a series of 81 limbs in which the clinical diagnosis of deep vein thrombosis was suspected, objective confirmation could be obtained in only 24 or 30%. Of the patients who presented with signs and symptoms of deep vein thrombosis confined to the calf, the diagnosis was confirmed in only 37%. In view of the attendant morbidity and mortality associated with anticoagulation therapy, it is suggested that in all patients in whom the clinical diagnosis of deep vein thrombosis is made, objective confirmation should be obtained by one or more of the currently available methods, before the initiation of long-term anticoagulation therapy.", "contents": "The need for objective diagnosis of deep vein thrombosis. In a series of 81 limbs in which the clinical diagnosis of deep vein thrombosis was suspected, objective confirmation could be obtained in only 24 or 30%. Of the patients who presented with signs and symptoms of deep vein thrombosis confined to the calf, the diagnosis was confirmed in only 37%. In view of the attendant morbidity and mortality associated with anticoagulation therapy, it is suggested that in all patients in whom the clinical diagnosis of deep vein thrombosis is made, objective confirmation should be obtained by one or more of the currently available methods, before the initiation of long-term anticoagulation therapy."} {"id": "PMID:1257865", "title": "The successful treatment of creeping eruption with topical thiabendazole.", "content": "Fifty patients with creeping eruption were treated topically with an aqueous suspension of 15% thiabendazole. A permanent cure was obtained in 94% of patients within a fortnight and in 98% within 3 weeks. No significant side-effects were encountered and at present topical thiabendazole is the treatment of choice for this condition.", "contents": "The successful treatment of creeping eruption with topical thiabendazole. Fifty patients with creeping eruption were treated topically with an aqueous suspension of 15% thiabendazole. A permanent cure was obtained in 94% of patients within a fortnight and in 98% within 3 weeks. No significant side-effects were encountered and at present topical thiabendazole is the treatment of choice for this condition."} {"id": "PMID:1257866", "title": "Difficult reduction of traumatic dislocation of the hip. A case report.", "content": "Difficulties in the reduction of a traumatic posterior dislocation of the hip, as a result of soft-tissue interposition, are uncommon. A case in which closed reduction was prevented by a partly detached labrum acetabulare is reported.", "contents": "Difficult reduction of traumatic dislocation of the hip. A case report. Difficulties in the reduction of a traumatic posterior dislocation of the hip, as a result of soft-tissue interposition, are uncommon. A case in which closed reduction was prevented by a partly detached labrum acetabulare is reported."} {"id": "PMID:1257867", "title": "Crystalloid versus colloid hemodilution in man.", "content": "The effects of intraoperative prebleeding and hemodilution with lactated Ringer's solution on hemodynamics, oxygen transport and lung water were studied in four patients undergoing extensive surgical procedures. The results were contrasted with those previously obtained from hemodilution of a group of patients with Plasmanate. The mean volumes bled were 1,950 milliliters in the lactated Ringer's solution group and 1,697 milliliters in the Plasmanate group. The posthemodilution hematocrit values were 26 per cent and 25 per cent, respectively. Cardiac output increased to only 115 per cent of the base line in the lactated Ringer's solution group but to 161 per cent in the Plasmanate group. Systemic oxygen transport was reduced to 80.0 per cent in the lactated Ringer's solution group, while in the Plasmanate group, it rose to 109.7 per cent. The lung water and alveolar arterial oxygen gradients were increased to 134 and 112 per cent in the lactated Ringer's solution group, whereas in the Plasmanate group, the lung water was reduced to 82 per cent, and the arterial alveolar oxygen gradient was reduced to 75 per cent. In these selected patients, hemodilution was well tolerated. Plasmanate hemodilution resulted in better compensatory changes than did hemodilution with lactated Ringer's solution in terms of oxygen transport and changes in lung water.", "contents": "Crystalloid versus colloid hemodilution in man. The effects of intraoperative prebleeding and hemodilution with lactated Ringer's solution on hemodynamics, oxygen transport and lung water were studied in four patients undergoing extensive surgical procedures. The results were contrasted with those previously obtained from hemodilution of a group of patients with Plasmanate. The mean volumes bled were 1,950 milliliters in the lactated Ringer's solution group and 1,697 milliliters in the Plasmanate group. The posthemodilution hematocrit values were 26 per cent and 25 per cent, respectively. Cardiac output increased to only 115 per cent of the base line in the lactated Ringer's solution group but to 161 per cent in the Plasmanate group. Systemic oxygen transport was reduced to 80.0 per cent in the lactated Ringer's solution group, while in the Plasmanate group, it rose to 109.7 per cent. The lung water and alveolar arterial oxygen gradients were increased to 134 and 112 per cent in the lactated Ringer's solution group, whereas in the Plasmanate group, the lung water was reduced to 82 per cent, and the arterial alveolar oxygen gradient was reduced to 75 per cent. In these selected patients, hemodilution was well tolerated. Plasmanate hemodilution resulted in better compensatory changes than did hemodilution with lactated Ringer's solution in terms of oxygen transport and changes in lung water."} {"id": "PMID:1257868", "title": "An analytic critique of existing classification systems for cancer of the breast.", "content": "The most popular systems of histologic typing for cancer of the breast have been analyzed as far as details of construction and results of application. The constituents of all systems are debatable. Lack of uniformity and standardization is obvious, while meaningful comparisons in terms of results and prognostic evaluation are unfeasible. Although the attempts to classify histologic patterns are hampered by the observers' variability and by the existence of different patterns within the same tumor, efforts have to be made to further standardize the terms used for designating histologic types. Additional aid can be expected from histologic grading and morphologic host defense reaction evaluation to substantiate the prognostic evaluation of individual cancers of the breast.", "contents": "An analytic critique of existing classification systems for cancer of the breast. The most popular systems of histologic typing for cancer of the breast have been analyzed as far as details of construction and results of application. The constituents of all systems are debatable. Lack of uniformity and standardization is obvious, while meaningful comparisons in terms of results and prognostic evaluation are unfeasible. Although the attempts to classify histologic patterns are hampered by the observers' variability and by the existence of different patterns within the same tumor, efforts have to be made to further standardize the terms used for designating histologic types. Additional aid can be expected from histologic grading and morphologic host defense reaction evaluation to substantiate the prognostic evaluation of individual cancers of the breast."} {"id": "PMID:1257869", "title": "Regional antibiotic infusion of the heart.", "content": "Regional arterial infusion of the heart and lung with an antibiotic did not increase the drug in the aortic serum to concentrations that would be clinically significant when compared with concentrations which can be attained by the intravenous method in a near normal functioning heart.", "contents": "Regional antibiotic infusion of the heart. Regional arterial infusion of the heart and lung with an antibiotic did not increase the drug in the aortic serum to concentrations that would be clinically significant when compared with concentrations which can be attained by the intravenous method in a near normal functioning heart."} {"id": "PMID:1257870", "title": "Therapeutic value of nafoxidine hydrochloride in the treatment of advanced carcinoma of the human breast.", "content": "Nafoxidine hydrochloride can provide additional palliation to patients who responded to previous endocrine ablation and had tumors containing an estrogen receptor. In the present study, 24 patients were evaluated for their response to nafoxidine therapy, 180 to 240 milligrams given orally per day. When tumor response was obtained, doses were reduced to 60 to 120 milligrams every other day or longer without loss of control. In the estrogen receptor positive group, eight of ten patients responded objectively to nafoxidine, while all seven estrogen receptor negative patients progressed with this therapy. These results demonstrated that nafoxidine is effective in the treatment of estrogen receptor positive cutaneous disease. These results demonstrated that nafoxidine is effective in the treatment of estrogen receptor positive cutaneous disease. Patients with lesions to other sites should receive cytoxic agents along with nafoxidine. Alternative therapy to nafoxidine should be considered for patients in whom the tumors contain negligible estrogen receptor.", "contents": "Therapeutic value of nafoxidine hydrochloride in the treatment of advanced carcinoma of the human breast. Nafoxidine hydrochloride can provide additional palliation to patients who responded to previous endocrine ablation and had tumors containing an estrogen receptor. In the present study, 24 patients were evaluated for their response to nafoxidine therapy, 180 to 240 milligrams given orally per day. When tumor response was obtained, doses were reduced to 60 to 120 milligrams every other day or longer without loss of control. In the estrogen receptor positive group, eight of ten patients responded objectively to nafoxidine, while all seven estrogen receptor negative patients progressed with this therapy. These results demonstrated that nafoxidine is effective in the treatment of estrogen receptor positive cutaneous disease. These results demonstrated that nafoxidine is effective in the treatment of estrogen receptor positive cutaneous disease. Patients with lesions to other sites should receive cytoxic agents along with nafoxidine. Alternative therapy to nafoxidine should be considered for patients in whom the tumors contain negligible estrogen receptor."} {"id": "PMID:1257871", "title": "Evaluation of pulmonary function in the ischemic expanded canine lung.", "content": "Twenty-four dogs underwent in vivo left pulmonary hilar occlusion with the lung continuously expanded at 10 centimeters or 25 centimeters of water pressure to determine the period of pulmonary ischemia that may be tolerated before consistent pulmonary edema and congestion develop after lung revascularization. Consistent and prolonged pulmonary edema and congestion that caused death of the dog occurred in at least one-half of the dogs when the period of hilar occlusion was extended beyond six hours. Elevation of the left pulmonary artery pressure was only a rough measurement of the severity of the anoxic pulmonary injury. Expansion of the lung at 10 centimeters of water continuous pressure was more beneficial than was expansion at 25 centimeters of pressure. Cyclic ventilation with slight negative-expiratory pressure provided less support to the lung than did continuous expansion at either pressure tested. Intial decreases in both ventilation and perfusion isotope uptake and the percentage of the total volume of oxygen uptake per minute by the ischemic lung returned to near normal levels in three weeks in dogs that survived. Lung expansion during periods of ischemia appears to prevent alveolar collapse and to facilitate oxygenation.", "contents": "Evaluation of pulmonary function in the ischemic expanded canine lung. Twenty-four dogs underwent in vivo left pulmonary hilar occlusion with the lung continuously expanded at 10 centimeters or 25 centimeters of water pressure to determine the period of pulmonary ischemia that may be tolerated before consistent pulmonary edema and congestion develop after lung revascularization. Consistent and prolonged pulmonary edema and congestion that caused death of the dog occurred in at least one-half of the dogs when the period of hilar occlusion was extended beyond six hours. Elevation of the left pulmonary artery pressure was only a rough measurement of the severity of the anoxic pulmonary injury. Expansion of the lung at 10 centimeters of water continuous pressure was more beneficial than was expansion at 25 centimeters of pressure. Cyclic ventilation with slight negative-expiratory pressure provided less support to the lung than did continuous expansion at either pressure tested. Intial decreases in both ventilation and perfusion isotope uptake and the percentage of the total volume of oxygen uptake per minute by the ischemic lung returned to near normal levels in three weeks in dogs that survived. Lung expansion during periods of ischemia appears to prevent alveolar collapse and to facilitate oxygenation."} {"id": "PMID:1257873", "title": "A simplified, improved techniqe for the Collis gastroplasty for dilatable esophageal strictures.", "content": "A safe, simple, effective and fast gastrophasty for the dilatable strictured esophagus has proved sound in dogs and feasible and effective in twenty-five patients. Several of the patients who had been operated upon elsewhere had recurrences. Postoperative follow-up studies of the 25 patients operated upon have revealed freedom from substernal pain, dysphagia, aspiration and bleeding in the upper part of the gastrointestinal tract. Encouraged by the success of the surgical techinique in patients with stricture of the esophagus, we have recently applied the same technique in the repair of hiatal hernia without stricture.", "contents": "A simplified, improved techniqe for the Collis gastroplasty for dilatable esophageal strictures. A safe, simple, effective and fast gastrophasty for the dilatable strictured esophagus has proved sound in dogs and feasible and effective in twenty-five patients. Several of the patients who had been operated upon elsewhere had recurrences. Postoperative follow-up studies of the 25 patients operated upon have revealed freedom from substernal pain, dysphagia, aspiration and bleeding in the upper part of the gastrointestinal tract. Encouraged by the success of the surgical techinique in patients with stricture of the esophagus, we have recently applied the same technique in the repair of hiatal hernia without stricture."} {"id": "PMID:1257874", "title": "Simulated acute appendicitis secondary to ventriculoperitoneal shunt.", "content": "A case of simulated acute appendicitis caused by a ventriculoperitoneal shunt is described. This case presented as a perplexing clinical problem. When the diagnosis was established by laparotomy, it was apparent that another complication should be added to the list of abdominal complications which occurred secondary to insertion of a ventriculoperitoneal shunt.", "contents": "Simulated acute appendicitis secondary to ventriculoperitoneal shunt. A case of simulated acute appendicitis caused by a ventriculoperitoneal shunt is described. This case presented as a perplexing clinical problem. When the diagnosis was established by laparotomy, it was apparent that another complication should be added to the list of abdominal complications which occurred secondary to insertion of a ventriculoperitoneal shunt."} {"id": "PMID:1257875", "title": "Hydrocephalus: I. Histological and ultrastructural changes in the pre-shunted cortical mantle.", "content": "Hydrocephalus results in a reduction in the thickness of the cerebral cortical mantle which seemingly is restored by ventricular shunting. In order to determine the effect of hydrocephalus and its potential reversibility, experimental hydrocephalus was produced in adult cats by the introduction of kaolin or silicone into the basal cisterns followed by bilateral craniectomies. Microscopic and fine structural studies of these animals suggest the occurrence of significant focal axonal destruction. These studies suggest a sequence of events consisting of ventriculomegaly, disruption of the periventricular ependyma, periventricular edema, axonal destruction, secondary myelin disintegration and finally reactive astrocytosis. The damage to axons and meylin and resulting gliosis is irreversible.", "contents": "Hydrocephalus: I. Histological and ultrastructural changes in the pre-shunted cortical mantle. Hydrocephalus results in a reduction in the thickness of the cerebral cortical mantle which seemingly is restored by ventricular shunting. In order to determine the effect of hydrocephalus and its potential reversibility, experimental hydrocephalus was produced in adult cats by the introduction of kaolin or silicone into the basal cisterns followed by bilateral craniectomies. Microscopic and fine structural studies of these animals suggest the occurrence of significant focal axonal destruction. These studies suggest a sequence of events consisting of ventriculomegaly, disruption of the periventricular ependyma, periventricular edema, axonal destruction, secondary myelin disintegration and finally reactive astrocytosis. The damage to axons and meylin and resulting gliosis is irreversible."} {"id": "PMID:1257876", "title": "Hydrocephalus: II. Cell number and size, and myelin content of the pre-shunted cerebral cortical mantle.", "content": "The number of cells in the brain and their size can be calculated by determining the total brain DNA, RNA and protein. Myelin can be determined biochemically. This analysis was applied to brains of a group of adult cats with craniectomies that were made severely hydrocephalilc by the introduction of kaolin or silicone into the basal cisterns. In severely hydrocephalic brains sectioned rostral to the area of kaolin inflammation there was no loss of dry weight. Wet weight increased slightly reflecting periventricular edema. There was a slight increase in total DNA, RNA and protein, presumably reflecting the increase in small inflammatory cells. There was a significant reduction in galactolipids reflecting myelin loss.", "contents": "Hydrocephalus: II. Cell number and size, and myelin content of the pre-shunted cerebral cortical mantle. The number of cells in the brain and their size can be calculated by determining the total brain DNA, RNA and protein. Myelin can be determined biochemically. This analysis was applied to brains of a group of adult cats with craniectomies that were made severely hydrocephalilc by the introduction of kaolin or silicone into the basal cisterns. In severely hydrocephalic brains sectioned rostral to the area of kaolin inflammation there was no loss of dry weight. Wet weight increased slightly reflecting periventricular edema. There was a slight increase in total DNA, RNA and protein, presumably reflecting the increase in small inflammatory cells. There was a significant reduction in galactolipids reflecting myelin loss."} {"id": "PMID:1257877", "title": "Frontal extradural hematomas.", "content": "In a series of 1841 severe head injuries, 97 cases of epidural hematomas were observed. Among these there were 13 in the frontal area, i.e. 13.4%. The nine cases of frontal extradural hematomas not previously reported are described. Five of them had \"pure\" extradural frontal clots. In four cases the epidural hematoma was associated with intradural lesions. The \"pure\" frontal epidural cases presented a subacute to chronic course of a benign character. All of these patients survived and made a complete recovery after operation. A malignant, stormy and fatal course was observed in the \"mixed\" cases.", "contents": "Frontal extradural hematomas. In a series of 1841 severe head injuries, 97 cases of epidural hematomas were observed. Among these there were 13 in the frontal area, i.e. 13.4%. The nine cases of frontal extradural hematomas not previously reported are described. Five of them had \"pure\" extradural frontal clots. In four cases the epidural hematoma was associated with intradural lesions. The \"pure\" frontal epidural cases presented a subacute to chronic course of a benign character. All of these patients survived and made a complete recovery after operation. A malignant, stormy and fatal course was observed in the \"mixed\" cases."} {"id": "PMID:1257878", "title": "Arteriovenous malformations of the anterior and the middle portions of the corpus callosum: microsurgical treatment.", "content": "The arterio-venous malformations of the corpus callosum are distinct clinical and surgical entities. Review of literature reveals 45 documented cases of which 32 were treated surgically. The authors (M.G.Y.) had 18 such patients of which eight involved the anterior and the middle portions of the corpus callosum. (No. 8 involved the whole callosum). The patients were in the younger age group. Headache and stiffness of the neck were the common presenting features. Seizures were rare and there was a paucity of localizing neurological signs. These AVMs are supplied mainly by the pericallosal arteries and occasionally by branches of the posterior cerebral artery. The drainage is by septal veins, the inferior sagittal sinus and the superior sagittal sinus. Radical excision of these AVMs in the anterior and the middle portions of the corpus callosum was accomplished without operative mortality and with minimal morbidity. Radical removal of these anomalies with microsurgical techniques is the treatment of choice.", "contents": "Arteriovenous malformations of the anterior and the middle portions of the corpus callosum: microsurgical treatment. The arterio-venous malformations of the corpus callosum are distinct clinical and surgical entities. Review of literature reveals 45 documented cases of which 32 were treated surgically. The authors (M.G.Y.) had 18 such patients of which eight involved the anterior and the middle portions of the corpus callosum. (No. 8 involved the whole callosum). The patients were in the younger age group. Headache and stiffness of the neck were the common presenting features. Seizures were rare and there was a paucity of localizing neurological signs. These AVMs are supplied mainly by the pericallosal arteries and occasionally by branches of the posterior cerebral artery. The drainage is by septal veins, the inferior sagittal sinus and the superior sagittal sinus. Radical excision of these AVMs in the anterior and the middle portions of the corpus callosum was accomplished without operative mortality and with minimal morbidity. Radical removal of these anomalies with microsurgical techniques is the treatment of choice."} {"id": "PMID:1257879", "title": "The anterior cerebral artery: I. Anatomo-radiological study of its cortical territories.", "content": "A comparative study and angiographic analysis of 24 brains were performed using selective radiopaque injections of the anterior cerebral artery. The arterial branches were projected on a model brain, using a bicommissural system of coordinates and a stereotaxic method as an encephalometric system of reference. Eleven constant cortical branches of the artery were demonstrated and their vascular territories demarcated.", "contents": "The anterior cerebral artery: I. Anatomo-radiological study of its cortical territories. A comparative study and angiographic analysis of 24 brains were performed using selective radiopaque injections of the anterior cerebral artery. The arterial branches were projected on a model brain, using a bicommissural system of coordinates and a stereotaxic method as an encephalometric system of reference. Eleven constant cortical branches of the artery were demonstrated and their vascular territories demarcated."} {"id": "PMID:1257880", "title": "Brain necrosis after repeated radiotherapy.", "content": "A case of radionecrosis in the brain simulating a tumor was presented. Two courses of radiotherapy were given to a right intraorbital tumor over an interval of ten years. Four years after the second course of therapy, symptoms simulating a right frontal lobe tumor developed. A frontal lobectomy including the necrotic area improved the patient's condition.", "contents": "Brain necrosis after repeated radiotherapy. A case of radionecrosis in the brain simulating a tumor was presented. Two courses of radiotherapy were given to a right intraorbital tumor over an interval of ten years. Four years after the second course of therapy, symptoms simulating a right frontal lobe tumor developed. A frontal lobectomy including the necrotic area improved the patient's condition."} {"id": "PMID:1257881", "title": "Super-selective arteriography of branches of the external carotid artery.", "content": "Superselective arteriography of the branches of the external carotid artery is of great value in the diagnosis of vascular lesions in the distribution of this artery. These include vascular anomalies of the scalp, the tongue, the ears, the face, the dura mater, and intracranial sinuses, of meningiomas, glomus tumors, angiofibromas of the nasopharynx, and metastases. Super-selective catheterization of the branch of the external carotid artery can also be utilized for the treatment of these lesions by embolization. The technique is described and the various lesions illustrated.", "contents": "Super-selective arteriography of branches of the external carotid artery. Superselective arteriography of the branches of the external carotid artery is of great value in the diagnosis of vascular lesions in the distribution of this artery. These include vascular anomalies of the scalp, the tongue, the ears, the face, the dura mater, and intracranial sinuses, of meningiomas, glomus tumors, angiofibromas of the nasopharynx, and metastases. Super-selective catheterization of the branch of the external carotid artery can also be utilized for the treatment of these lesions by embolization. The technique is described and the various lesions illustrated."} {"id": "PMID:1257882", "title": "Reversal of aphasia with superficial temporal artery to middle cerebral artery anastomosis.", "content": "Two patients with aphasia which markedly regressed following superficial temporal to middle cerebral artery anastomoses are reported. Added to the armamentarium of stroke therapy for the amelioration of focal ischemic disease, modern microvascular techniques allow the establishment of collaterals to recipient vessels of less than 1 mm in diameter. A neurological deficit which is supposed to be permanent is usually considered a contraindication to these procedures. This report details two cases in which aphasia and motor weakness markedly improved following a superficial temporal artery to middle cerebral artery anastomosis.", "contents": "Reversal of aphasia with superficial temporal artery to middle cerebral artery anastomosis. Two patients with aphasia which markedly regressed following superficial temporal to middle cerebral artery anastomoses are reported. Added to the armamentarium of stroke therapy for the amelioration of focal ischemic disease, modern microvascular techniques allow the establishment of collaterals to recipient vessels of less than 1 mm in diameter. A neurological deficit which is supposed to be permanent is usually considered a contraindication to these procedures. This report details two cases in which aphasia and motor weakness markedly improved following a superficial temporal artery to middle cerebral artery anastomosis."} {"id": "PMID:1257884", "title": "Timing of pentobarbital administration for brain protection in experimental stroke.", "content": "Significant reduction of experimentally induced cerebral infarction was associated in the canine model with the administration of pentobarbital at one hour postocclusion but not thereafter.", "contents": "Timing of pentobarbital administration for brain protection in experimental stroke. Significant reduction of experimentally induced cerebral infarction was associated in the canine model with the administration of pentobarbital at one hour postocclusion but not thereafter."} {"id": "PMID:1257885", "title": "Intracranial pressure gradients in a patient with a thalamic tumor.", "content": "The clinical history and intracranial pressure records of a patient with a thalamic tumor obstructing the ventricular system is presented. There were sustained differences in pressure between the anterior and posterior parts of the obstructed lateral ventricle. Brain compliance was markedly reduced and there were numerous pressure waves. It is believed that these supratentorial pressure gradients are most marked when there is a loss of brain compliance, and that they contribute to the mechanisms of brain shifts and spreading edema. Thus, they must be taken into account in the management of patients with intracranial mass lesions.", "contents": "Intracranial pressure gradients in a patient with a thalamic tumor. The clinical history and intracranial pressure records of a patient with a thalamic tumor obstructing the ventricular system is presented. There were sustained differences in pressure between the anterior and posterior parts of the obstructed lateral ventricle. Brain compliance was markedly reduced and there were numerous pressure waves. It is believed that these supratentorial pressure gradients are most marked when there is a loss of brain compliance, and that they contribute to the mechanisms of brain shifts and spreading edema. Thus, they must be taken into account in the management of patients with intracranial mass lesions."} {"id": "PMID:1257888", "title": "Extradural extrusion of roots of the cauda equina.", "content": "For lumbar spondylotic stenosis causing progressive disability, multiple laminectomy was about to be completed. Suddenly roots of the cauda equina herniated through the myelography puncture site in the dura mater, resembling redundant nerve roots. This case is being reported not only because such sudden extradural extrusion is rare, but also to raise the question of the relationship of redundancy of nerve roots to spondylotic stenosis.", "contents": "Extradural extrusion of roots of the cauda equina. For lumbar spondylotic stenosis causing progressive disability, multiple laminectomy was about to be completed. Suddenly roots of the cauda equina herniated through the myelography puncture site in the dura mater, resembling redundant nerve roots. This case is being reported not only because such sudden extradural extrusion is rare, but also to raise the question of the relationship of redundancy of nerve roots to spondylotic stenosis."} {"id": "PMID:1257889", "title": "Epidermoid cyst of the third ventricle.", "content": "The authors report a case of a cystic epidermoid of the third ventricle in a young female presenting with headache and mental disturbances. The cyst filled completely with gas during ventriculography and was subtotally removed through an interhemispheric callosal-splitting approach.", "contents": "Epidermoid cyst of the third ventricle. The authors report a case of a cystic epidermoid of the third ventricle in a young female presenting with headache and mental disturbances. The cyst filled completely with gas during ventriculography and was subtotally removed through an interhemispheric callosal-splitting approach."} {"id": "PMID:1257890", "title": "The edema of cerebral contusion.", "content": "A model is described for study of the cerebral edema associated with the contusion of closed head injury. A Remington Humane Stunner was used to deliver blows to the skulls of anesthetized cats. Forty-eight hours after impact, those cats demonstrating a one-sided contusion were tested for cerebral edema by measurement of the decrease in density (specific gravity) of white matter from normal values. Significant change in tissue density was seen in the white matter of contused hemispheres. Hemispheres with contusion limited to the cortex (gray matter) showed a change in tissue density which was considerably less than that seen in hemispheres with contusion involving both gray and white matter.", "contents": "The edema of cerebral contusion. A model is described for study of the cerebral edema associated with the contusion of closed head injury. A Remington Humane Stunner was used to deliver blows to the skulls of anesthetized cats. Forty-eight hours after impact, those cats demonstrating a one-sided contusion were tested for cerebral edema by measurement of the decrease in density (specific gravity) of white matter from normal values. Significant change in tissue density was seen in the white matter of contused hemispheres. Hemispheres with contusion limited to the cortex (gray matter) showed a change in tissue density which was considerably less than that seen in hemispheres with contusion involving both gray and white matter."} {"id": "PMID:1257891", "title": "Acute hemorrhagic cerebellar infarction following angiography.", "content": "Cerebellar infarction following cerebral angiography is an unusual complication. A case is reported. The patient's condition deteriorated with each diagnostic study. Improvement occurred after cerebellar decompression and evacuation of an intracerebellar hematoma.", "contents": "Acute hemorrhagic cerebellar infarction following angiography. Cerebellar infarction following cerebral angiography is an unusual complication. A case is reported. The patient's condition deteriorated with each diagnostic study. Improvement occurred after cerebellar decompression and evacuation of an intracerebellar hematoma."} {"id": "PMID:1257892", "title": "Hydrocephalus: III. Reconstitution of the cerebral cortical mantle following ventricular shunting.", "content": "Adult cats with hydrocephalus were sacrificed at varying times following valveless ventricular shunting. This shunting resulted in a prompt reduction of ventricular size and rapid gross reconstitution of cortical mantle. Ultrastructurally it was evident that white matter edema persisted for many weeks, even in the presence of normal size ventricles. The areas most severely affected by the hydrocephalus such as the corpus callosum showed a paucity of myelinated fibers and their replacement by numerous reactive astrocytes. Reconstitution of the cortical mantle consists predominantly of a diminution of white matter edema and reactive astrocytosis. Clinical improvement undoubtly results from the functional improvement of remaining elements rather than from the replacement of lost elements. This scheme of hydrocephalus suggests that if hydrocephalus is relieved when only ependymal disruption and periventricular water accumulation have occurred, it may be reversible. The subsequent sequence of events consisting of axonal degeneration, myelin disruption and reactive astrocytosis may be less, if at all reversible.", "contents": "Hydrocephalus: III. Reconstitution of the cerebral cortical mantle following ventricular shunting. Adult cats with hydrocephalus were sacrificed at varying times following valveless ventricular shunting. This shunting resulted in a prompt reduction of ventricular size and rapid gross reconstitution of cortical mantle. Ultrastructurally it was evident that white matter edema persisted for many weeks, even in the presence of normal size ventricles. The areas most severely affected by the hydrocephalus such as the corpus callosum showed a paucity of myelinated fibers and their replacement by numerous reactive astrocytes. Reconstitution of the cortical mantle consists predominantly of a diminution of white matter edema and reactive astrocytosis. Clinical improvement undoubtly results from the functional improvement of remaining elements rather than from the replacement of lost elements. This scheme of hydrocephalus suggests that if hydrocephalus is relieved when only ependymal disruption and periventricular water accumulation have occurred, it may be reversible. The subsequent sequence of events consisting of axonal degeneration, myelin disruption and reactive astrocytosis may be less, if at all reversible."} {"id": "PMID:1257894", "title": "The physics of the cranial cavity, hydrocephalus and normal pressure hydrocephalus: mechanical interpretation and mathematical model.", "content": "It is intended for this research, to provide some basis for the understanding of the rational mechanics of the cranial content. There are many interesting and controversial facts derived from the experimental and clinical-pathological observations of hydrocephalus and increased intracranial pressure. For instance, in some patients a moderate increase of intracranial pressure is accompanied by hydrocephalus and mental changes, while in others, with high intracranial pressure, the ventricles and mental functions remain unaltered. What then is the parameter that changes the size of the ventricles and impairs brain function? It is shown how the transmission of intraventricular pressure throughout the brain parenchyma creates a stress distribution that varies in magnitude; how during the production, maintenance, and reversal of hydrocephalus, and normal pressure hydrocephalus the stress is distributed throughout the brain; and how in the presence of a sudden increase of intracranial pressure nature has arranged additional mechanisms for protecting the brain. It is important to recognize that some aspects of intracranial physiopathology can be explained through classical concepts of physics, prior to attempting to interpret such processes solely in terms of biological or auto-regulatory phenomena.", "contents": "The physics of the cranial cavity, hydrocephalus and normal pressure hydrocephalus: mechanical interpretation and mathematical model. It is intended for this research, to provide some basis for the understanding of the rational mechanics of the cranial content. There are many interesting and controversial facts derived from the experimental and clinical-pathological observations of hydrocephalus and increased intracranial pressure. For instance, in some patients a moderate increase of intracranial pressure is accompanied by hydrocephalus and mental changes, while in others, with high intracranial pressure, the ventricles and mental functions remain unaltered. What then is the parameter that changes the size of the ventricles and impairs brain function? It is shown how the transmission of intraventricular pressure throughout the brain parenchyma creates a stress distribution that varies in magnitude; how during the production, maintenance, and reversal of hydrocephalus, and normal pressure hydrocephalus the stress is distributed throughout the brain; and how in the presence of a sudden increase of intracranial pressure nature has arranged additional mechanisms for protecting the brain. It is important to recognize that some aspects of intracranial physiopathology can be explained through classical concepts of physics, prior to attempting to interpret such processes solely in terms of biological or auto-regulatory phenomena."} {"id": "PMID:1257895", "title": "Arterial plasma amino acids in patients with serious postoperative infection and in patients with major fractures.", "content": "Arterial plasma amino acids were measured in 27 patients with serious septic complications after operation, 15 patients following reduction of femoral shaft fractures and nine control patients on the first and third days following uneventful major abdominal surgery. Amino acid concentrations in the controls were similar to those which have been reported during early starvation. The amino acid patterns seen in all groups did not resemble that previously observed following glucocorticoid administration. In the patients with infection, mean phenylalanine concentration (108.0 +/- 46.9 mumoles per liter) was significantly greater than in the controls on the first (p greater than 0.001) or third (p less than 0.001) postoperative days. Four of the septic patients with hyperphenylalaninemia also had elevated arterial methionine concentrations. These observations suggest that many of the patients with sepsis had seriously impaired liver metabolism. In patients with fractures, the concentrations of ornithine (p less than 0.001), taurine (p less than 0.05), and aspartic acid (p less than 0.05) were lower than in controls. No other significant differences of amino acid concentrations were observed. It is difficult to relate these differences to a specific metabolic abnormality.", "contents": "Arterial plasma amino acids in patients with serious postoperative infection and in patients with major fractures. Arterial plasma amino acids were measured in 27 patients with serious septic complications after operation, 15 patients following reduction of femoral shaft fractures and nine control patients on the first and third days following uneventful major abdominal surgery. Amino acid concentrations in the controls were similar to those which have been reported during early starvation. The amino acid patterns seen in all groups did not resemble that previously observed following glucocorticoid administration. In the patients with infection, mean phenylalanine concentration (108.0 +/- 46.9 mumoles per liter) was significantly greater than in the controls on the first (p greater than 0.001) or third (p less than 0.001) postoperative days. Four of the septic patients with hyperphenylalaninemia also had elevated arterial methionine concentrations. These observations suggest that many of the patients with sepsis had seriously impaired liver metabolism. In patients with fractures, the concentrations of ornithine (p less than 0.001), taurine (p less than 0.05), and aspartic acid (p less than 0.05) were lower than in controls. No other significant differences of amino acid concentrations were observed. It is difficult to relate these differences to a specific metabolic abnormality."} {"id": "PMID:1257896", "title": "The effects of severe progressive hemodilution on regional blood flow and oxygen consumption.", "content": "Electrolyte solutions are effective in the immediate treatment of hemorrhagic shock, but the acceptable limits of hemodilution are not well defined. In this study oxygen consumption was measured in various tissues at rest and in maximally exercising skeletal muscle during progressive hemodilution. Twenty splenectomized, anesthetized dogs were studied (weight 22.6 +/- 2.0 kilograms). Measurements were made of cardiac output, capillary muscle blood flow in the hind limb, and renal and superior mesenteric arterial blood flow. Arteriovenous oxygen differences in the hind limb, kidney, gut, and in the whole body were calculated from the oxygen content of arterial and appropriate venous samples.", "contents": "The effects of severe progressive hemodilution on regional blood flow and oxygen consumption. Electrolyte solutions are effective in the immediate treatment of hemorrhagic shock, but the acceptable limits of hemodilution are not well defined. In this study oxygen consumption was measured in various tissues at rest and in maximally exercising skeletal muscle during progressive hemodilution. Twenty splenectomized, anesthetized dogs were studied (weight 22.6 +/- 2.0 kilograms). Measurements were made of cardiac output, capillary muscle blood flow in the hind limb, and renal and superior mesenteric arterial blood flow. Arteriovenous oxygen differences in the hind limb, kidney, gut, and in the whole body were calculated from the oxygen content of arterial and appropriate venous samples."} {"id": "PMID:1257897", "title": "Anaerobic infections in surgery: clinical review.", "content": "Anaerobic bacteria are being recognized with increasing frequency as important micro-organisms in surgical infections. Clostridium, Bacteriodes, Fusobacterium, and Peptostreptococcus are the clinically prominent pathological anaerobes. All are commensals and, consequently, most anaerobic infections are endogenous in origin. In the colon, anaerobes are 1,000 times more prevalent than aerobes. This has important implications regarding the management of gastrointestinal tract operations and the treatment of infections originating from the bowel. Typical anaerobic infections include gas gangrene, brain abscess, oral infections, putrid lung abscesses, intra-abdominal abscesses, and wound infections following gynecologic and bowel surgery, perirectal abscesses, postabortal infections, and septic thrombophlebitis. Infections with anaerobic organisms must be suspected when there is feculent odor and/or gas production following gynecologic or bowel surgery, when there are organisms on gram staining but no growth on aerobic cultures, or when septicemia is associated with repeatedly negative blood cultures. Debridement and drainage constitute the main stay of treatment. All anaerobes are sensitive to chloramphenicol and clindamycin and all but Bacteroides fragils are sensitive to penicillin. Identification of anaerobes requires proper specimen sampling, immediate culturing on prereduced media, and careful gram staining of clinical material. The frequency of anaerobic organisms in surgical infections generally is not recognized by many surgeons; their importance needs to be stressed in the future.", "contents": "Anaerobic infections in surgery: clinical review. Anaerobic bacteria are being recognized with increasing frequency as important micro-organisms in surgical infections. Clostridium, Bacteriodes, Fusobacterium, and Peptostreptococcus are the clinically prominent pathological anaerobes. All are commensals and, consequently, most anaerobic infections are endogenous in origin. In the colon, anaerobes are 1,000 times more prevalent than aerobes. This has important implications regarding the management of gastrointestinal tract operations and the treatment of infections originating from the bowel. Typical anaerobic infections include gas gangrene, brain abscess, oral infections, putrid lung abscesses, intra-abdominal abscesses, and wound infections following gynecologic and bowel surgery, perirectal abscesses, postabortal infections, and septic thrombophlebitis. Infections with anaerobic organisms must be suspected when there is feculent odor and/or gas production following gynecologic or bowel surgery, when there are organisms on gram staining but no growth on aerobic cultures, or when septicemia is associated with repeatedly negative blood cultures. Debridement and drainage constitute the main stay of treatment. All anaerobes are sensitive to chloramphenicol and clindamycin and all but Bacteroides fragils are sensitive to penicillin. Identification of anaerobes requires proper specimen sampling, immediate culturing on prereduced media, and careful gram staining of clinical material. The frequency of anaerobic organisms in surgical infections generally is not recognized by many surgeons; their importance needs to be stressed in the future."} {"id": "PMID:1257898", "title": "Autologus saphenous vein femoropopliteal bypass: analysis of 298 cases.", "content": "A retrospective review of 298 saphenous vein femoropopliteal bypasses performed for femoral artery occlusive disease over a 13 year period was carried out. The purpose of the study was to assess factors which influence long-term graft patency. Follow-up was 95.3 percent complete. Results were analyzed with the aid of IBM data processing equipment and standard statistical methods.", "contents": "Autologus saphenous vein femoropopliteal bypass: analysis of 298 cases. A retrospective review of 298 saphenous vein femoropopliteal bypasses performed for femoral artery occlusive disease over a 13 year period was carried out. The purpose of the study was to assess factors which influence long-term graft patency. Follow-up was 95.3 percent complete. Results were analyzed with the aid of IBM data processing equipment and standard statistical methods."} {"id": "PMID:1257899", "title": "Localization of peripheral catheter emboli with xeroradiography.", "content": "There is an increasing incidence of venous catheter emboli coincident with the prolonged use of both peripheral and central venous cannuli. Difficulty in localizing embolized catheter fragments frequently has been a problem, especially in the pediatric patient in whom nonradiopaque catheters are used. A case of catheter embolus in a 4-week-old infant is reported and the use of xeroradiography to localize the catheter in the soft tissue of the extremity is described. Xeroradiography offers excellent definition of soft tissue architecture and therefore may be of value in a variety of situations where localization of a foreign body proves difficult.", "contents": "Localization of peripheral catheter emboli with xeroradiography. There is an increasing incidence of venous catheter emboli coincident with the prolonged use of both peripheral and central venous cannuli. Difficulty in localizing embolized catheter fragments frequently has been a problem, especially in the pediatric patient in whom nonradiopaque catheters are used. A case of catheter embolus in a 4-week-old infant is reported and the use of xeroradiography to localize the catheter in the soft tissue of the extremity is described. Xeroradiography offers excellent definition of soft tissue architecture and therefore may be of value in a variety of situations where localization of a foreign body proves difficult."} {"id": "PMID:1257900", "title": "Renal function after thermal trauma: the effects of treatment on renal blood flow and sodium and water excretion.", "content": "Effective renal plasma flow, urine sodium excretion, and glomerular filtration rates were reduced markedly to 44%, 46%, and 60% of normal, respectively, in rats subjected to thermal trauma. A sodium load of about 2 mEq. per 100 Gm. of body weight restores these functions toward normal. Doubling the concomitant water load had no discernible beneficial effect, but rats resuscitated with the larger water load were in greater positive water balance. These experimental data suggest that the water loads commonly administered clinically for the treatment of burn shock may be unnecessarily large.", "contents": "Renal function after thermal trauma: the effects of treatment on renal blood flow and sodium and water excretion. Effective renal plasma flow, urine sodium excretion, and glomerular filtration rates were reduced markedly to 44%, 46%, and 60% of normal, respectively, in rats subjected to thermal trauma. A sodium load of about 2 mEq. per 100 Gm. of body weight restores these functions toward normal. Doubling the concomitant water load had no discernible beneficial effect, but rats resuscitated with the larger water load were in greater positive water balance. These experimental data suggest that the water loads commonly administered clinically for the treatment of burn shock may be unnecessarily large."} {"id": "PMID:1257901", "title": "Regional hemodynamics of large and small femoral arteriovenous fistulas in dogs.", "content": "Alterations in regional hemodynamics were determined after construction of side-to-side femoral arteriovenous fistulas in dogs to quantitate the relationship between fistula size and reversal of distal arterial blood flow. When fistula size exceeded the transverse diameter of the femoral artery and vein (large fistula group), reversal in distal arterial blood flow was observed in all fistulas and measured 48 +/- 7 ml. per minute. If the fistula size were approximately equal to these critical transverse diameters (small fistula group), distal arterial flow was reduced but reversal did not occur. Distal arterial and venous pressures were 42 +/- 5 and 35 +/- 4 mn. Hg, respectively, for the large fistula group, and these pressures were 79 +/- 5 and 17 +/- 2 mn. Ht, respectively, for the small fistula group. These pressure changes for the two groups were significantly different and may provide a better understanding of the physiology of the reversal phenomenon.", "contents": "Regional hemodynamics of large and small femoral arteriovenous fistulas in dogs. Alterations in regional hemodynamics were determined after construction of side-to-side femoral arteriovenous fistulas in dogs to quantitate the relationship between fistula size and reversal of distal arterial blood flow. When fistula size exceeded the transverse diameter of the femoral artery and vein (large fistula group), reversal in distal arterial blood flow was observed in all fistulas and measured 48 +/- 7 ml. per minute. If the fistula size were approximately equal to these critical transverse diameters (small fistula group), distal arterial flow was reduced but reversal did not occur. Distal arterial and venous pressures were 42 +/- 5 and 35 +/- 4 mn. Hg, respectively, for the large fistula group, and these pressures were 79 +/- 5 and 17 +/- 2 mn. Ht, respectively, for the small fistula group. These pressure changes for the two groups were significantly different and may provide a better understanding of the physiology of the reversal phenomenon."} {"id": "PMID:1257902", "title": "Directional arterial flow velocity: a sensitive index of changes in peripheral vascular resistance.", "content": "The effect of peripheral vascular resistance of directional arterial flow velocity was determined utilizing the directional Doppler velocity detector under experimental conditions. Femoral arterial resistance was increased and decreased, and arterial pressure, venous pressure, volume flow, and directional flow velocity were measured in the femoral artery. An increase in peripheral vascular resistance was associated with a marked increase in reverse flow and a decrease in forward flow velocity. Reverse flow decreased and forward flow velocity increased when resistance was lowered. The ratio of peak and mean reverse/forward (r/f) flow velocity changed in a linear relationship with vascular resistance. The increase in resistance associated with progressive hypovolemia was paralleled by an increase in r/f flow velocity which occurred before blood pressure declined. Thus alterations in directional arterial flow velocity can be used as a sensitive indicator of changes in peripheral vascular resistance.", "contents": "Directional arterial flow velocity: a sensitive index of changes in peripheral vascular resistance. The effect of peripheral vascular resistance of directional arterial flow velocity was determined utilizing the directional Doppler velocity detector under experimental conditions. Femoral arterial resistance was increased and decreased, and arterial pressure, venous pressure, volume flow, and directional flow velocity were measured in the femoral artery. An increase in peripheral vascular resistance was associated with a marked increase in reverse flow and a decrease in forward flow velocity. Reverse flow decreased and forward flow velocity increased when resistance was lowered. The ratio of peak and mean reverse/forward (r/f) flow velocity changed in a linear relationship with vascular resistance. The increase in resistance associated with progressive hypovolemia was paralleled by an increase in r/f flow velocity which occurred before blood pressure declined. Thus alterations in directional arterial flow velocity can be used as a sensitive indicator of changes in peripheral vascular resistance."} {"id": "PMID:1257903", "title": "Air embolization during the machine preservation of kidney.", "content": "Air embolization during machine preservation of kidneys for transplantation occurred in seven of 218 kidneys. In three it occured during transportation on a portable machine. On arrival they had warmed up and were discarded. In four kidneys air embolization occured in the laboratory and was detected immediately. Upon re-establishment of perfusion, there was a sharply lower flow and a higher diastolic pressure. Within 30 to 120 minutes the flow reached the pre-embolization rate and the diastolic pressure stabilized at a slightly higher level than before embolization. One recipient died 2 months after transplantation due to infection, and one kidney was removed because of rejection after 32 days. Two patients receiving the mates to the above kidneys were discharged with excellent kidney function. If the exact time of air embolization cannot be determined, it is prudent to discard the kidneys. This indicates the importance of continuous supervision during the perfusion. When air embolization occurs in the laboratory and is detected immediately, the kidney should be evaluated carefully. If, after correction of the defect, the perfusion and diastolic pressure reach the neighborhood of pre-embolization levels within 30 to 120 minutes with no patchy discoloration, the kidney is suitable for transportation. Discarding kidneys with air emboli without proper evaluation is not justifiable.", "contents": "Air embolization during the machine preservation of kidney. Air embolization during machine preservation of kidneys for transplantation occurred in seven of 218 kidneys. In three it occured during transportation on a portable machine. On arrival they had warmed up and were discarded. In four kidneys air embolization occured in the laboratory and was detected immediately. Upon re-establishment of perfusion, there was a sharply lower flow and a higher diastolic pressure. Within 30 to 120 minutes the flow reached the pre-embolization rate and the diastolic pressure stabilized at a slightly higher level than before embolization. One recipient died 2 months after transplantation due to infection, and one kidney was removed because of rejection after 32 days. Two patients receiving the mates to the above kidneys were discharged with excellent kidney function. If the exact time of air embolization cannot be determined, it is prudent to discard the kidneys. This indicates the importance of continuous supervision during the perfusion. When air embolization occurs in the laboratory and is detected immediately, the kidney should be evaluated carefully. If, after correction of the defect, the perfusion and diastolic pressure reach the neighborhood of pre-embolization levels within 30 to 120 minutes with no patchy discoloration, the kidney is suitable for transportation. Discarding kidneys with air emboli without proper evaluation is not justifiable."} {"id": "PMID:1257904", "title": "Spontaneous rupture of the rectosigmoid colon with anal evisceration: a new complication of uterine prolapse.", "content": "Spontaneous large bowel perforations have been associated with chronic constipation. The previously reported episodes of anal evisceration of small intestine have occurred in patients with a rectal prolapse. An end-stage complication of chronic third degree uterine prolapse is presented. A laceration of the anterior rectosignoid colon wall permitted small bowel extrusion through the anus. The tearing effect exerted by the prolapsed uterus at the rectouterine fold presumably caused the rectosigmoid laceration.", "contents": "Spontaneous rupture of the rectosigmoid colon with anal evisceration: a new complication of uterine prolapse. Spontaneous large bowel perforations have been associated with chronic constipation. The previously reported episodes of anal evisceration of small intestine have occurred in patients with a rectal prolapse. An end-stage complication of chronic third degree uterine prolapse is presented. A laceration of the anterior rectosignoid colon wall permitted small bowel extrusion through the anus. The tearing effect exerted by the prolapsed uterus at the rectouterine fold presumably caused the rectosigmoid laceration."} {"id": "PMID:1257905", "title": "The nonoperative treatment of massive pyloroduodenal hemorrhage by retracted autologous clot embolization.", "content": "Six patients with massive pyloroduodenal hemorrhage were treated by selective embolization of retracted autologous clot to occlude the bleeding vessels. All patients had severe associated illnesses and were very poor candidates for operative treatment. The actively bleeding vessel was occluded successfully and hemorrhage was controlled with autologous clot alone in five of these patients, although two patients later bled from other sites. Although three patients died, none died as a direct result of bleeding. The only complication encountered, multiple small hepatic infarct, occurred when the embolized clot migrated from the gastroduodenal artery to the hepatic artery. A method of avoiding this complication is presented. Selective emolization of retracted autologous clot represents a useful alternative to the operative management of massive pyloroduodenal hemorrhage and should be considered for the treatment of patients whose associated diseases make them poor candidates for operative treatment.", "contents": "The nonoperative treatment of massive pyloroduodenal hemorrhage by retracted autologous clot embolization. Six patients with massive pyloroduodenal hemorrhage were treated by selective embolization of retracted autologous clot to occlude the bleeding vessels. All patients had severe associated illnesses and were very poor candidates for operative treatment. The actively bleeding vessel was occluded successfully and hemorrhage was controlled with autologous clot alone in five of these patients, although two patients later bled from other sites. Although three patients died, none died as a direct result of bleeding. The only complication encountered, multiple small hepatic infarct, occurred when the embolized clot migrated from the gastroduodenal artery to the hepatic artery. A method of avoiding this complication is presented. Selective emolization of retracted autologous clot represents a useful alternative to the operative management of massive pyloroduodenal hemorrhage and should be considered for the treatment of patients whose associated diseases make them poor candidates for operative treatment."} {"id": "PMID:1257906", "title": "Giant esophageal leiomyoma with secondary megaesophagus.", "content": "A 25-year-old woman presented with a giant leiomyoma in the lower third of the esophagus. She had no digestive symptoms, although there was a severe esophageal dilation. Such a megaesophagus secondary to a leiomyoma has not been described previously. Esophagogastric resection was performed, followed by an uneventful recovery period. The literature on esophageal leiomyoma is reviewed.", "contents": "Giant esophageal leiomyoma with secondary megaesophagus. A 25-year-old woman presented with a giant leiomyoma in the lower third of the esophagus. She had no digestive symptoms, although there was a severe esophageal dilation. Such a megaesophagus secondary to a leiomyoma has not been described previously. Esophagogastric resection was performed, followed by an uneventful recovery period. The literature on esophageal leiomyoma is reviewed."} {"id": "PMID:1257907", "title": "A pressure-measuring system for long-term in vivo pressure measurements.", "content": "A new balloon-tipped catheter has been developed for the purpose of making long-term vivo intravascular pressure measurements. Among its advantages are its ability to electrically isolate the subject from the pressure transducer and be rebalanced and calibrated while in situ. Experimental results in calves indicate that the system provides a very reliable means of calibrating implanted catheter tip pressure transducers in situ and can be used as the primary long-term pressure measuring device when high frequency response is not required.", "contents": "A pressure-measuring system for long-term in vivo pressure measurements. A new balloon-tipped catheter has been developed for the purpose of making long-term vivo intravascular pressure measurements. Among its advantages are its ability to electrically isolate the subject from the pressure transducer and be rebalanced and calibrated while in situ. Experimental results in calves indicate that the system provides a very reliable means of calibrating implanted catheter tip pressure transducers in situ and can be used as the primary long-term pressure measuring device when high frequency response is not required."} {"id": "PMID:1257908", "title": "The mechanism of increased gallstone formation in obese human subjects.", "content": "Cholesterol gallstones occur three times more frequently in morbidly obese subjects than in normal controls. The present study tests the hypothesis that obese subjects develop gallstones because of relative and absolute excess cholesterol excretion in bile. The steady-state kinetics of biliary lipid excretion and bile acid pool sizes were determined in eight healthy obese subjects without gallstones by a noninvasive technique. Aliquots of resting gallbladder bile were obtained on consecutive days. Hepatic bile excretion was constantly sampled during the infusion of a liquid isocaloric cholesterol-free formula containing a dilution indicator over two 12 hour periods on consecutive days. Gallbladder bile of seven of eight subjects was saturated consistently with cholesterol. Mean hourly hepatic cholesterol excretion in bile was 0.232 mM. per hour, three times greater than that of normal subjects and twice that of subjects with gallstones. Phospholipid and bile acid excretion were 0.73 and 1.88 mM. per hour, respectively. The excretion rates of these cholesterol-solubilizing components of bile are higher than in normal subjects but are insufficient to compensate for the increased cholesterol excretion. The bile acid pool sizes were normal (X = 2.72 Gm.) but the daily synthesis of bile acids was increased (X = 0.86 Gm. of cholic acid). We conclude that the clinically observed high correlation of cholelithiasis with obesity is due to increased hepatic secretion of cholesterol which precipitates as cholesterol gallstones.", "contents": "The mechanism of increased gallstone formation in obese human subjects. Cholesterol gallstones occur three times more frequently in morbidly obese subjects than in normal controls. The present study tests the hypothesis that obese subjects develop gallstones because of relative and absolute excess cholesterol excretion in bile. The steady-state kinetics of biliary lipid excretion and bile acid pool sizes were determined in eight healthy obese subjects without gallstones by a noninvasive technique. Aliquots of resting gallbladder bile were obtained on consecutive days. Hepatic bile excretion was constantly sampled during the infusion of a liquid isocaloric cholesterol-free formula containing a dilution indicator over two 12 hour periods on consecutive days. Gallbladder bile of seven of eight subjects was saturated consistently with cholesterol. Mean hourly hepatic cholesterol excretion in bile was 0.232 mM. per hour, three times greater than that of normal subjects and twice that of subjects with gallstones. Phospholipid and bile acid excretion were 0.73 and 1.88 mM. per hour, respectively. The excretion rates of these cholesterol-solubilizing components of bile are higher than in normal subjects but are insufficient to compensate for the increased cholesterol excretion. The bile acid pool sizes were normal (X = 2.72 Gm.) but the daily synthesis of bile acids was increased (X = 0.86 Gm. of cholic acid). We conclude that the clinically observed high correlation of cholelithiasis with obesity is due to increased hepatic secretion of cholesterol which precipitates as cholesterol gallstones."} {"id": "PMID:1257909", "title": "A new vascular access for hemodialysis: the arterial jump graft.", "content": "In seven patients in whom conventional vascular access for maintenance hemodialysis was not possible, a new access in the form of a femoropopliteal jump graft was employed. A follow-up of 3 months to 3 years (92 patient months) and an experience of more than 1,000 dialysis treatments have shown it to be a stable and satisfactory access.", "contents": "A new vascular access for hemodialysis: the arterial jump graft. In seven patients in whom conventional vascular access for maintenance hemodialysis was not possible, a new access in the form of a femoropopliteal jump graft was employed. A follow-up of 3 months to 3 years (92 patient months) and an experience of more than 1,000 dialysis treatments have shown it to be a stable and satisfactory access."} {"id": "PMID:1257910", "title": "Pneumatosis cystoides intestinalis: an unusual complication of jejunoileal bypass.", "content": "A case of pneumatosis cytoides intestinalis associated with jejunoileal bypass is reported. The association of increased colonic gas, secondary to fermentation of undigested lactose in the colon, and the reflux of the excessive gas into the excluded segment of small bowel and dissection of the gas into the bowel wall and mesentery are postulated as the causes of pneumatosis cystoides intestinalis in patients with jejunoileal bypass.", "contents": "Pneumatosis cystoides intestinalis: an unusual complication of jejunoileal bypass. A case of pneumatosis cytoides intestinalis associated with jejunoileal bypass is reported. The association of increased colonic gas, secondary to fermentation of undigested lactose in the colon, and the reflux of the excessive gas into the excluded segment of small bowel and dissection of the gas into the bowel wall and mesentery are postulated as the causes of pneumatosis cystoides intestinalis in patients with jejunoileal bypass."} {"id": "PMID:1257912", "title": "(14C)Ethylenethiourea: distribution, excretion, and metabolism in pregnant rats.", "content": "Following administration of single oral doses of [14C]ethylenethiourea (ETU) to pregnant rats maternal blood maintained peak radioactivity for 2 h, and the radioactivity was dispersed uniformly between the red blood cells and plasma. The level of radioactivity was distributed equally among several maternal tissues but was present in lower amounts in embryos. Twenty-four hours after treatment all tissues examined, except blood, were relatively clear of radioactivity and 72.8% of the total radioactivity given had been excreted in the urine. Elution patterns of metabolites from Sephadex separation suggested that ethylenethiourea was degraded very little. The teratological mechanism is discussed.", "contents": "(14C)Ethylenethiourea: distribution, excretion, and metabolism in pregnant rats. Following administration of single oral doses of [14C]ethylenethiourea (ETU) to pregnant rats maternal blood maintained peak radioactivity for 2 h, and the radioactivity was dispersed uniformly between the red blood cells and plasma. The level of radioactivity was distributed equally among several maternal tissues but was present in lower amounts in embryos. Twenty-four hours after treatment all tissues examined, except blood, were relatively clear of radioactivity and 72.8% of the total radioactivity given had been excreted in the urine. Elution patterns of metabolites from Sephadex separation suggested that ethylenethiourea was degraded very little. The teratological mechanism is discussed."} {"id": "PMID:1257929", "title": "High peptic stricture of the oesophagus.", "content": "Fifty-seven patients with high peptic stricture and the lower oesophagus lined by columnar epithelium are considered from the clinical point of view. Information from 115 cases of low stricture is introduced for comparison. The average age of adult patients was 62 years with a sex incidence of 36 females to 21 males. There is little difference between the symptoms of high and low strictures. Radiologically, the majority of high strictures are short and smooth but other types are illustrated. Carcinoma and congenital mid-oesophageal web are considered in the differential diagnosis. There was an associated duodenal ulcer in 10% of cases. In six patients, a high stricture developed soon after an abdominal operation or period of recumbency. Two patients are illustrated showing the process of stricture formation. Four patients are described who had gastric-lined oesophagus but no ulceration of stricture. One patient had a Barrett ulcer in addition to a high stricture. A patient is described in whom the mucosa of the lower oesophagus appeared to be replaced by jejunal mucosa following oesophagojejunostomy. One patient is illustrated in whom a stricture was seen to ascend the oesophagus over a period of six years. Thirty-three patients were treated by dilatation and 24 by operation. Hernial repair is an effective form of treatment. Of 19 patients treated in this way, significant dysphagia persisted in two and slight dysphagia in one. The clinical findings are discussed in relation to the origin of columnar epithelium in the oesophagus.", "contents": "High peptic stricture of the oesophagus. Fifty-seven patients with high peptic stricture and the lower oesophagus lined by columnar epithelium are considered from the clinical point of view. Information from 115 cases of low stricture is introduced for comparison. The average age of adult patients was 62 years with a sex incidence of 36 females to 21 males. There is little difference between the symptoms of high and low strictures. Radiologically, the majority of high strictures are short and smooth but other types are illustrated. Carcinoma and congenital mid-oesophageal web are considered in the differential diagnosis. There was an associated duodenal ulcer in 10% of cases. In six patients, a high stricture developed soon after an abdominal operation or period of recumbency. Two patients are illustrated showing the process of stricture formation. Four patients are described who had gastric-lined oesophagus but no ulceration of stricture. One patient had a Barrett ulcer in addition to a high stricture. A patient is described in whom the mucosa of the lower oesophagus appeared to be replaced by jejunal mucosa following oesophagojejunostomy. One patient is illustrated in whom a stricture was seen to ascend the oesophagus over a period of six years. Thirty-three patients were treated by dilatation and 24 by operation. Hernial repair is an effective form of treatment. Of 19 patients treated in this way, significant dysphagia persisted in two and slight dysphagia in one. The clinical findings are discussed in relation to the origin of columnar epithelium in the oesophagus."} {"id": "PMID:1257930", "title": "Pulmonary varix.", "content": "Pulmonary varix is a rare disorder which is usually discovered by change during the third to sixth decade in an asymptomatic patient. The 37th example is reported with a review of the literature. The disorder is possibly congenital and may affect any lobe. Pulmonary angiography is the preferred procedure for diagnosis. If symptoms are present, they can usually attributed to associated cardiopulmonary disease. Two serious complications have been reported--systematic embolus from a clot in the varix (two cases suspected), and rupture leading to the death of the patient (four cases). A third hazard to the patient is an unnecessary diagnostic thoracotomy. Patients without symptoms should have periodic chest radiographs of those with haemoptysis or systemic embolism should be considered for resection of the varix.", "contents": "Pulmonary varix. Pulmonary varix is a rare disorder which is usually discovered by change during the third to sixth decade in an asymptomatic patient. The 37th example is reported with a review of the literature. The disorder is possibly congenital and may affect any lobe. Pulmonary angiography is the preferred procedure for diagnosis. If symptoms are present, they can usually attributed to associated cardiopulmonary disease. Two serious complications have been reported--systematic embolus from a clot in the varix (two cases suspected), and rupture leading to the death of the patient (four cases). A third hazard to the patient is an unnecessary diagnostic thoracotomy. Patients without symptoms should have periodic chest radiographs of those with haemoptysis or systemic embolism should be considered for resection of the varix."} {"id": "PMID:1257931", "title": "Mitral incompetence and ventricular septal defects following non-penetrating injury.", "content": "A case of mitral incompetence and multiple ventricular septal defects following a non-penetrating chest injury is described. Cardiac injury was detected by electrocardiogram and by the appearance of a heart murmur in the second week after trauma. Superimposition of bacterial endocarditis seven years later caused cardiac decompensation and necessitated successful surgical treatment. Previous reported cases are reviewed.", "contents": "Mitral incompetence and ventricular septal defects following non-penetrating injury. A case of mitral incompetence and multiple ventricular septal defects following a non-penetrating chest injury is described. Cardiac injury was detected by electrocardiogram and by the appearance of a heart murmur in the second week after trauma. Superimposition of bacterial endocarditis seven years later caused cardiac decompensation and necessitated successful surgical treatment. Previous reported cases are reviewed."} {"id": "PMID:1257932", "title": "Resection of a leiomyoma of the descending thoracic aorta.", "content": "A primary aortic neoplasm in a 4-year-old asymptomatic boy is described. At operation the tumour was found to originate from the descending thoracici aorta. Histologically it proved to be a leiomyoma. The operative findings and pathological features are briefly discussed.", "contents": "Resection of a leiomyoma of the descending thoracic aorta. A primary aortic neoplasm in a 4-year-old asymptomatic boy is described. At operation the tumour was found to originate from the descending thoracici aorta. Histologically it proved to be a leiomyoma. The operative findings and pathological features are briefly discussed."} {"id": "PMID:1257933", "title": "Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients.", "content": "An analysis is made of the results of pleuropneumonectomy for diffuse malignant pleural mesothelioma in 29 patients and a comparison is made with the results of non-surgical treatment in a further 17 patients. A system of tumour staging is proposed, and the results are correlated with tumour stage and with histological type. Pleuropneumonectomy does not appear materially to affect the course of the disease in cases of mixed epithelial and mesenchymal histological type. However, stage I cases of pure epithelial histological type appear to carry a better prognosis, especially those whose histological structure consists entirely of abundant oedematous mucoid stroma with loosely arranged tumour cells. It is suggested therefore that only epithelial cases should be subjected to pleuropneumonectomy. Means of reducing operative mortality are discussed and alternative methods of treatment described.", "contents": "Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. An analysis is made of the results of pleuropneumonectomy for diffuse malignant pleural mesothelioma in 29 patients and a comparison is made with the results of non-surgical treatment in a further 17 patients. A system of tumour staging is proposed, and the results are correlated with tumour stage and with histological type. Pleuropneumonectomy does not appear materially to affect the course of the disease in cases of mixed epithelial and mesenchymal histological type. However, stage I cases of pure epithelial histological type appear to carry a better prognosis, especially those whose histological structure consists entirely of abundant oedematous mucoid stroma with loosely arranged tumour cells. It is suggested therefore that only epithelial cases should be subjected to pleuropneumonectomy. Means of reducing operative mortality are discussed and alternative methods of treatment described."} {"id": "PMID:1257934", "title": "Chronic bronchitis--measurements and observations over 10 years.", "content": "A total of 111 patients with chronic bronchitis were selected for study in 1963. By 1974 only 54 patients were available for clinical examination, chest radiography, and pulmonary function measurements. There was a significantly higher mortality compared with men of the same age and in the same locality, and this was due to cardiorespiratory failure and bronchial carcinoma. Reduction of cigarette smoking, declining atmospheric pollution, and antibiotic treatment have reduced the 24-hour sputum volume of these patients. The initial one-second forced expiratory volume (FEV1) and vital capacity were significantly lower in those patients who later died from cardio-respiratory failure. The duration of antibiotic treatment and the smoking record have not significantly affected the decline of the FEV1 with advancing age. The transfer factor (diffusing capacity) for carbon monoxide (TF) has declined more in those who continued to smoke. Of the 54 patients 14 had radiological evidence of emphysema initially. This has shown little change over 10 years.", "contents": "Chronic bronchitis--measurements and observations over 10 years. A total of 111 patients with chronic bronchitis were selected for study in 1963. By 1974 only 54 patients were available for clinical examination, chest radiography, and pulmonary function measurements. There was a significantly higher mortality compared with men of the same age and in the same locality, and this was due to cardiorespiratory failure and bronchial carcinoma. Reduction of cigarette smoking, declining atmospheric pollution, and antibiotic treatment have reduced the 24-hour sputum volume of these patients. The initial one-second forced expiratory volume (FEV1) and vital capacity were significantly lower in those patients who later died from cardio-respiratory failure. The duration of antibiotic treatment and the smoking record have not significantly affected the decline of the FEV1 with advancing age. The transfer factor (diffusing capacity) for carbon monoxide (TF) has declined more in those who continued to smoke. Of the 54 patients 14 had radiological evidence of emphysema initially. This has shown little change over 10 years."} {"id": "PMID:1257935", "title": "Baritosis: a benign pneumoconiosis.", "content": "Baritosis is one of the benign pneumoconioses in which inhaled particulate matter lies in the lungs for years without producing symptoms, abnormal physical signs, incapacity for work, interference with lung function, or liability to develop pulmonary or bronchial infections or other thoracic disease. Owing to the high radio-opacity of barium, the discrete shadows in the chest radiograph are extremely dense. Even in the most well-marked cases with extreme profusion of the opacities, massive shadows do not occur. When exposure to barium dust ceases the opacities begin slowly to disappear. Nine cases of baritosis occurring in a small factory in which barytes was crushed, graded, and milled are described. Two of the cases occurred after only 18 and 21 month's exposure, and 9 of the 10 men employed for more than one and a half years had baritosis. Five of the affected men examined at intervals since their exposure to barytes ceased in 1964 showed marked clearing of their radiological abnormalities.", "contents": "Baritosis: a benign pneumoconiosis. Baritosis is one of the benign pneumoconioses in which inhaled particulate matter lies in the lungs for years without producing symptoms, abnormal physical signs, incapacity for work, interference with lung function, or liability to develop pulmonary or bronchial infections or other thoracic disease. Owing to the high radio-opacity of barium, the discrete shadows in the chest radiograph are extremely dense. Even in the most well-marked cases with extreme profusion of the opacities, massive shadows do not occur. When exposure to barium dust ceases the opacities begin slowly to disappear. Nine cases of baritosis occurring in a small factory in which barytes was crushed, graded, and milled are described. Two of the cases occurred after only 18 and 21 month's exposure, and 9 of the 10 men employed for more than one and a half years had baritosis. Five of the affected men examined at intervals since their exposure to barytes ceased in 1964 showed marked clearing of their radiological abnormalities."} {"id": "PMID:1257936", "title": "Cartilage in children's lungs: a quantitative assessment using the right middle lobe.", "content": "The amount and development of cartilage in the lungs of 150 children dying between 24 week's gestation and 12 years has been studied using standard sections of the right middle lobe. Both the cartilage-bearing bronchi and the cartilage fragments increase in number until approximately two months after birth, after which time a constant level is maintained. There is a progressive increase in the total area of cartilage in the child's lung during infancy and childhood, and this appears to be more directly related to the crown-rump length of the child than to its age. Percentiles of the quantity of cartilage found in the standard lung sections are presented.", "contents": "Cartilage in children's lungs: a quantitative assessment using the right middle lobe. The amount and development of cartilage in the lungs of 150 children dying between 24 week's gestation and 12 years has been studied using standard sections of the right middle lobe. Both the cartilage-bearing bronchi and the cartilage fragments increase in number until approximately two months after birth, after which time a constant level is maintained. There is a progressive increase in the total area of cartilage in the child's lung during infancy and childhood, and this appears to be more directly related to the crown-rump length of the child than to its age. Percentiles of the quantity of cartilage found in the standard lung sections are presented."} {"id": "PMID:1257937", "title": "Conservative surgery for bronchial adenomata.", "content": "Fifteen patients with bronchial adenomata have undergone surgical treatment and have been followed up for periods of one to 25 years. Management consisted of bronchotomy with local excision in six cases, segmental resection in two, lobectomy in six, and pneumonectomy in one case. One patient who underwent lobectomy subsequently died of an unrelated cause (gastric haemorrhage) in the early postoperative period; of the remaining 14, there have been no cases of recurrence, and all patients have remained sympton-free with normal chest radiographs. These results strongly support a conservative surgical approach where the clinical and histological diagnosis of carcinoid tumour is definite.", "contents": "Conservative surgery for bronchial adenomata. Fifteen patients with bronchial adenomata have undergone surgical treatment and have been followed up for periods of one to 25 years. Management consisted of bronchotomy with local excision in six cases, segmental resection in two, lobectomy in six, and pneumonectomy in one case. One patient who underwent lobectomy subsequently died of an unrelated cause (gastric haemorrhage) in the early postoperative period; of the remaining 14, there have been no cases of recurrence, and all patients have remained sympton-free with normal chest radiographs. These results strongly support a conservative surgical approach where the clinical and histological diagnosis of carcinoid tumour is definite."} {"id": "PMID:1257938", "title": "Acute aortic dissection and medial degeneration in patients with 'floppy' mitral valves.", "content": "Mitral regurgitation due to 'floppy' valves is frequently associated with areas of medical necrosis in the ascending aorta. Application of the aortic clamp to such an area during valve replacement may produce an intimal tear followed by acute dissection. This complication occurred in three patients and was treated successfully by repair of the tear in the two cases where the dissection was observed at the time of operation. Is is suggested that infrequent clamping of the aorta and careful control of the pefusion pressure may decrease the risk of intimal trauma and acute dissection.", "contents": "Acute aortic dissection and medial degeneration in patients with 'floppy' mitral valves. Mitral regurgitation due to 'floppy' valves is frequently associated with areas of medical necrosis in the ascending aorta. Application of the aortic clamp to such an area during valve replacement may produce an intimal tear followed by acute dissection. This complication occurred in three patients and was treated successfully by repair of the tear in the two cases where the dissection was observed at the time of operation. Is is suggested that infrequent clamping of the aorta and careful control of the pefusion pressure may decrease the risk of intimal trauma and acute dissection."} {"id": "PMID:1257939", "title": "Elective operations for post-infarction left ventricular aneurysms.", "content": "During a two-year period (February 1973 to February 1975) 20 consecutive patients with post-infarction left ventricular aneurysm, seen at the Wessex Cardiac and Thoracic Centre, underwent aneurysmectomy with or without aorta-to-coronary artery saphenous vein bypass grafts, ventricular septal defect closure, or valve replacement. The diagnoses were established by clinical means, plain chest radiographs, left ventriculography, and selective coronary arteriography. The indications for surgery were uncontrollable congestive heart failure and angina, ventricular arrhythmias, or a rapidly growing aneurysm. Low cardiac indices or high left ventricular end-diastolic pressure were not considered to be contraindications to operation. Resection of the left ventricular aneurysm was performed with the use of normothermic cardiopulmonary bypass with haemodilution. In addition to the aneurysmectomy, four of these patients had concomitant closure of post-infarction ventricular septal defects; four had valve replacements; two had grafts to coronary arteries; and one had both replacement of the mitral valve and a right coronary vein graft. There were two hospital deaths (10%) and two late deaths (10%), making an overall mortality of 20%. All but one of the deaths were related to coronary artery disease. The survivors are active, and their rehabilitation was satisfactory. The longest survivor is doing well two years after left ventricular aneurysmectomy, ventricular defect closure, and tricuspid valve replacement. It is evident from our experience and from the reports of others that surgery has an established place in the management of post-infarction left ventricular aneurysm.", "contents": "Elective operations for post-infarction left ventricular aneurysms. During a two-year period (February 1973 to February 1975) 20 consecutive patients with post-infarction left ventricular aneurysm, seen at the Wessex Cardiac and Thoracic Centre, underwent aneurysmectomy with or without aorta-to-coronary artery saphenous vein bypass grafts, ventricular septal defect closure, or valve replacement. The diagnoses were established by clinical means, plain chest radiographs, left ventriculography, and selective coronary arteriography. The indications for surgery were uncontrollable congestive heart failure and angina, ventricular arrhythmias, or a rapidly growing aneurysm. Low cardiac indices or high left ventricular end-diastolic pressure were not considered to be contraindications to operation. Resection of the left ventricular aneurysm was performed with the use of normothermic cardiopulmonary bypass with haemodilution. In addition to the aneurysmectomy, four of these patients had concomitant closure of post-infarction ventricular septal defects; four had valve replacements; two had grafts to coronary arteries; and one had both replacement of the mitral valve and a right coronary vein graft. There were two hospital deaths (10%) and two late deaths (10%), making an overall mortality of 20%. All but one of the deaths were related to coronary artery disease. The survivors are active, and their rehabilitation was satisfactory. The longest survivor is doing well two years after left ventricular aneurysmectomy, ventricular defect closure, and tricuspid valve replacement. It is evident from our experience and from the reports of others that surgery has an established place in the management of post-infarction left ventricular aneurysm."} {"id": "PMID:1257940", "title": "Dead space ventilation in normal children and children with obstructive airways diease.", "content": "Anatomical dead space was measured in 72 normal children aged from 5 to 16 years, using the single breath method. There was a linear increase in this measurement with height, weight, and end-inspiratory lung volume. Physiological dead space was measured in 52 normal children using the Bohr equation and substituting a rebreathing PCO2 for alveolar PCO2. There was a parallel increase in this measurement with height, weight, and end-inspiratory lung volume. The difference between the two dead space measurements constitutes the alveolar dead space and was constant over the whole age range at 45 +/- 22 ml. The ratio of physiological dead space to tidal volume was 33-6 +/-4-6% and was unaltered by age or change in lung volume. The effect of airways obstruction on the dead space volumes was studied in 36 children with asthma and 28 with cystic fibrosis. Physiological dead space increased with increasing airways obstruction. Anatomical dead space remained constant in spite of marked increases in lung volume associated with the airways obstruction.", "contents": "Dead space ventilation in normal children and children with obstructive airways diease. Anatomical dead space was measured in 72 normal children aged from 5 to 16 years, using the single breath method. There was a linear increase in this measurement with height, weight, and end-inspiratory lung volume. Physiological dead space was measured in 52 normal children using the Bohr equation and substituting a rebreathing PCO2 for alveolar PCO2. There was a parallel increase in this measurement with height, weight, and end-inspiratory lung volume. The difference between the two dead space measurements constitutes the alveolar dead space and was constant over the whole age range at 45 +/- 22 ml. The ratio of physiological dead space to tidal volume was 33-6 +/-4-6% and was unaltered by age or change in lung volume. The effect of airways obstruction on the dead space volumes was studied in 36 children with asthma and 28 with cystic fibrosis. Physiological dead space increased with increasing airways obstruction. Anatomical dead space remained constant in spite of marked increases in lung volume associated with the airways obstruction."} {"id": "PMID:1257941", "title": "A PATHOLOGICAL study of the lungs and heart in fatal and non-fatal chronic airways obstruction.", "content": "The lungs and hearts from 50 patients were examined using morphometric techniques to determine the size of the right ventricle, the amount, type, and distribution of emphysema, the size of the bronchial mucous glands, and the proportion of the lung occupied by small airways of less than 2 mm diameter. The patients were divided into three groups according to the clinical history: 18 died as a result of chronic airways obstruction, 17 had symptoms of chronic chest disease but died from some unrelated cause, and 15 had no symptoms related to the respiratory system. The total amount of emphysema was found to be greater in the fatal than the symptomatic group who in turn had more emphysema than the asymptomatic group. A positive correlation was found between the amount of emphysema and the right ventricular weight. The amount of panlobular emphysema in the lung was found to be greater in the fatal group than in the others but this did not apply to the amount of centrilobular emphysema. The amount of panlobular, but not centrilobular, emphysema showed a positive correlation with right ventricular weight. As the total amount of emphysema increased it was found that there was an increase in each of three zones in the lung-apical, middle, and lower. There was no relationship between the bronchial mucous gland size and either the clinical state of the patients with symptoms or the right ventricular weight. The proportion of lung occupied by the lumen of small airways was significantly reduced in the fatal group as compared to the other two groups and also showed a negative (inverse) correlation with right ventricular weight. The total amount of emphysema, the amount of panlobular emphysema, and reduction in small airways lumen in the lung are the three factors in chronic airways obstruction which are quantitatively related to death in chronic airways obstruction and to right ventricular weight.", "contents": "A PATHOLOGICAL study of the lungs and heart in fatal and non-fatal chronic airways obstruction. The lungs and hearts from 50 patients were examined using morphometric techniques to determine the size of the right ventricle, the amount, type, and distribution of emphysema, the size of the bronchial mucous glands, and the proportion of the lung occupied by small airways of less than 2 mm diameter. The patients were divided into three groups according to the clinical history: 18 died as a result of chronic airways obstruction, 17 had symptoms of chronic chest disease but died from some unrelated cause, and 15 had no symptoms related to the respiratory system. The total amount of emphysema was found to be greater in the fatal than the symptomatic group who in turn had more emphysema than the asymptomatic group. A positive correlation was found between the amount of emphysema and the right ventricular weight. The amount of panlobular emphysema in the lung was found to be greater in the fatal group than in the others but this did not apply to the amount of centrilobular emphysema. The amount of panlobular, but not centrilobular, emphysema showed a positive correlation with right ventricular weight. As the total amount of emphysema increased it was found that there was an increase in each of three zones in the lung-apical, middle, and lower. There was no relationship between the bronchial mucous gland size and either the clinical state of the patients with symptoms or the right ventricular weight. The proportion of lung occupied by the lumen of small airways was significantly reduced in the fatal group as compared to the other two groups and also showed a negative (inverse) correlation with right ventricular weight. The total amount of emphysema, the amount of panlobular emphysema, and reduction in small airways lumen in the lung are the three factors in chronic airways obstruction which are quantitatively related to death in chronic airways obstruction and to right ventricular weight."} {"id": "PMID:1257942", "title": "Influence of long-term intermittent exposures to hypoxia on decompression-induced pulmonary haemorrhage.", "content": "Healthy male rats were acclimatized by being placed in a decompression chamber at a simulated altitude of 18 000 feet (5486 m) for three hours daily for 84 days. The altitude acclimatized rats paired with unacclimatized rats were rapidly decompressed together. The range of decompression was performed from on atmospheric pressure to an ambient pressure of 30 mmHg in 0-2 seconds. It was found that in control rats, 14 of 20 lung (70%) exhibited pulmonary haemorrhage following rapid decompression. In altitude acclimatized rats, however, only 6 of 20 (30%) revealed decompression-induced haemorrhage. The difference was statistically significant. The present findings indicate that long-term intermittent exposures to hypoxia might increase the resistance of pulmonary tissue to rapid decompression, resulting in a decrease in frequency and severity of pulmonary haemorrhage. The possible mechanism of such a phenomenon is discussed.", "contents": "Influence of long-term intermittent exposures to hypoxia on decompression-induced pulmonary haemorrhage. Healthy male rats were acclimatized by being placed in a decompression chamber at a simulated altitude of 18 000 feet (5486 m) for three hours daily for 84 days. The altitude acclimatized rats paired with unacclimatized rats were rapidly decompressed together. The range of decompression was performed from on atmospheric pressure to an ambient pressure of 30 mmHg in 0-2 seconds. It was found that in control rats, 14 of 20 lung (70%) exhibited pulmonary haemorrhage following rapid decompression. In altitude acclimatized rats, however, only 6 of 20 (30%) revealed decompression-induced haemorrhage. The difference was statistically significant. The present findings indicate that long-term intermittent exposures to hypoxia might increase the resistance of pulmonary tissue to rapid decompression, resulting in a decrease in frequency and severity of pulmonary haemorrhage. The possible mechanism of such a phenomenon is discussed."} {"id": "PMID:1258041", "title": "[Veterinary medicine and prevention of cruelty to animals: a paradox?].", "content": "The fact that veterinary medicine is associated with the protection of the welfare of animals in intensive live-stock farming is increasingly coming to be regarded as not being an inconsistency. The veterinarian has various responsibilities in this regard, to the stock farmer who has to make money out of his animals but whose goodwill in society will also depend on the welfare of the animals, and, finally, to the other members of his profession and himself. When the housing of the animals is altered, stock farmers will require some support. However, an increase in costs and a possible decline in competetive position should not be allowed to stand in the way of essential improvements.", "contents": "[Veterinary medicine and prevention of cruelty to animals: a paradox?]. The fact that veterinary medicine is associated with the protection of the welfare of animals in intensive live-stock farming is increasingly coming to be regarded as not being an inconsistency. The veterinarian has various responsibilities in this regard, to the stock farmer who has to make money out of his animals but whose goodwill in society will also depend on the welfare of the animals, and, finally, to the other members of his profession and himself. When the housing of the animals is altered, stock farmers will require some support. However, an increase in costs and a possible decline in competetive position should not be allowed to stand in the way of essential improvements."} {"id": "PMID:1258042", "title": "[Welfare or absence of welfare in farm animals (author's transl)].", "content": "A particular adjustment of the Live-Stock Act in the Netherlands is advocated in a brief comment on problems of welfare in intensive live-stock farming. The appointment of veterinary inspectors under the Veterinary Service may provide both temporary solutions and permanent supervision. The necessary knowledge and flexibility as well as a committee of arbitration will be essential in this scheme. This would also appear to be in accordance with suggestions by the Minister of Agriculture. International co-ordination and settlement of financial consequences are a prerequisite. Further studies on the veterinary criteria of animal welfare will be required in addition to an ethological approach.", "contents": "[Welfare or absence of welfare in farm animals (author's transl)]. A particular adjustment of the Live-Stock Act in the Netherlands is advocated in a brief comment on problems of welfare in intensive live-stock farming. The appointment of veterinary inspectors under the Veterinary Service may provide both temporary solutions and permanent supervision. The necessary knowledge and flexibility as well as a committee of arbitration will be essential in this scheme. This would also appear to be in accordance with suggestions by the Minister of Agriculture. International co-ordination and settlement of financial consequences are a prerequisite. Further studies on the veterinary criteria of animal welfare will be required in addition to an ethological approach."} {"id": "PMID:1258043", "title": "[Transport of animals prior to slaughter (author's transl)].", "content": "The transport of animals prior to slaughter is discussed in broad outline. Attention is paid to the need for adjustment and harmonisation of legislation in this field. It is pointed out that veterinary advice on and interest in the transport of animals has been wanting. Methods designed to improve matters and to ensure a more efficient approach to the problem are reviewed.", "contents": "[Transport of animals prior to slaughter (author's transl)]. The transport of animals prior to slaughter is discussed in broad outline. Attention is paid to the need for adjustment and harmonisation of legislation in this field. It is pointed out that veterinary advice on and interest in the transport of animals has been wanting. Methods designed to improve matters and to ensure a more efficient approach to the problem are reviewed."} {"id": "PMID:1258044", "title": "[Transport of live-stock and process of slaughter (author's transl)].", "content": "The introduction on the transport of live-stock and the process of slaughter is mainly confined to transport and stunning as part of the processing of pigs as this presents a fair picture of the problems which also arise in the case of other animals. The study was promoted by problems of welfare both in the animals and in the people involved as well as by the need for modernization. The problems are due particularly to the advent of scale economies in slaughter-houses, the law failing to adjust itselt with sufficient rapidity. These problems will be solved most effectively by a good understanding between and interplay of research institutes and, for instance, the various executive veterinary services.", "contents": "[Transport of live-stock and process of slaughter (author's transl)]. The introduction on the transport of live-stock and the process of slaughter is mainly confined to transport and stunning as part of the processing of pigs as this presents a fair picture of the problems which also arise in the case of other animals. The study was promoted by problems of welfare both in the animals and in the people involved as well as by the need for modernization. The problems are due particularly to the advent of scale economies in slaughter-houses, the law failing to adjust itselt with sufficient rapidity. These problems will be solved most effectively by a good understanding between and interplay of research institutes and, for instance, the various executive veterinary services."} {"id": "PMID:1258045", "title": "[Veterinarians and experimental animals - duties and rights (author's transl)].", "content": "Well over one million warm-blooded experimental animals are used in the Netherlands every year. The community is socially responsible for the purposes of research. The team of investigators is responsible for the scientific and technical merits of the experimental study, and this responsibility is based on the special knowledge and skill of those concerned. The future Laboratory Animal Act will not be able to ensure \"the rights of animals\" by rigid rules. The Act is effective in that it: (a) affords guarantees that experts (including veterinarians having expert knowledge of the care and management of laboratory animals, veterinary inspectors and animal technicians) will assist at experiments on animals and, (b) will make available that data of laboratory animals and types of experiment, which is essential to the proper functioning of social responsibility. The veterinarian having expert knowledge of the care and management of laboratory animals should take steps to ensure that the stress to which animals are exposed in experimental studies is not in excess of the value of the experiment. His attention should therefore be directed to the health and uniformity of the experimental animals, the methods adopted in experimental procedures, the training of animal technicians and medical or biological students, instruction of intending research workers, providing literature on experimental animals and normal values, advice on experimental designs and the choice of an animal model.", "contents": "[Veterinarians and experimental animals - duties and rights (author's transl)]. Well over one million warm-blooded experimental animals are used in the Netherlands every year. The community is socially responsible for the purposes of research. The team of investigators is responsible for the scientific and technical merits of the experimental study, and this responsibility is based on the special knowledge and skill of those concerned. The future Laboratory Animal Act will not be able to ensure \"the rights of animals\" by rigid rules. The Act is effective in that it: (a) affords guarantees that experts (including veterinarians having expert knowledge of the care and management of laboratory animals, veterinary inspectors and animal technicians) will assist at experiments on animals and, (b) will make available that data of laboratory animals and types of experiment, which is essential to the proper functioning of social responsibility. The veterinarian having expert knowledge of the care and management of laboratory animals should take steps to ensure that the stress to which animals are exposed in experimental studies is not in excess of the value of the experiment. His attention should therefore be directed to the health and uniformity of the experimental animals, the methods adopted in experimental procedures, the training of animal technicians and medical or biological students, instruction of intending research workers, providing literature on experimental animals and normal values, advice on experimental designs and the choice of an animal model."} {"id": "PMID:1258073", "title": "[A way to spatial irradiation planning. III. Further information on the procedure for obtaining dose homogeneity in noncoplanar ray beams and its experimental verification].", "content": "The method is based on the following principle: Single, initally unsettled parameters of irradiation are determined by explicit calculation in such a way that the dose gradient resulting from the dose gradients of the single ray beams in the point of intersection of their axes becomes zero. The separation or addition of components of the gradients is performed by use of co-ordinates for the ray beam as well as for the body. The following parameters can be determined explicitly: First, the weights of the partial doses which are to form the total dose in the point of intersection and/or second, the angles of the wedges and/or third, the rotational angles of the wedge filters, i. e. the angles of rotation of the wedge filters about an axis corresponding to the central ray. In the course of the following experimental verification of the method, maximally possible dose homogeneity results within the area of the crossing ray beams. Moreover, the advantages of field arrangements with different planes of incidence are coming into view.", "contents": "[A way to spatial irradiation planning. III. Further information on the procedure for obtaining dose homogeneity in noncoplanar ray beams and its experimental verification]. The method is based on the following principle: Single, initally unsettled parameters of irradiation are determined by explicit calculation in such a way that the dose gradient resulting from the dose gradients of the single ray beams in the point of intersection of their axes becomes zero. The separation or addition of components of the gradients is performed by use of co-ordinates for the ray beam as well as for the body. The following parameters can be determined explicitly: First, the weights of the partial doses which are to form the total dose in the point of intersection and/or second, the angles of the wedges and/or third, the rotational angles of the wedge filters, i. e. the angles of rotation of the wedge filters about an axis corresponding to the central ray. In the course of the following experimental verification of the method, maximally possible dose homogeneity results within the area of the crossing ray beams. Moreover, the advantages of field arrangements with different planes of incidence are coming into view."} {"id": "PMID:1258074", "title": "[A way to spatial irradiation planning. IV. Examples of radiotherapeutic practice and conclusions].", "content": "The method described in detail in part III of this paper aims at an optimization of dose distributions with regard to homogeneity within the common area of intersection of the ray beams concerned; now, practical planning is achieved with good results. Common clinical examples are treated, but of such a kind that dose homogeneity is not to be obtained without difficulty, either because of the chosen arrangement of fields within different planes of incidence or on other grounds. Finally, the advantages, practical possibilities and limits of the method indicated are thoroughly discussed.", "contents": "[A way to spatial irradiation planning. IV. Examples of radiotherapeutic practice and conclusions]. The method described in detail in part III of this paper aims at an optimization of dose distributions with regard to homogeneity within the common area of intersection of the ray beams concerned; now, practical planning is achieved with good results. Common clinical examples are treated, but of such a kind that dose homogeneity is not to be obtained without difficulty, either because of the chosen arrangement of fields within different planes of incidence or on other grounds. Finally, the advantages, practical possibilities and limits of the method indicated are thoroughly discussed."} {"id": "PMID:1258075", "title": "[Experience in peritoneography, for the prevention of the primary complications during intraperitoneal instillation of radiogold].", "content": "Prior to intraabdominal radiogold therapy of the ovarian carcinoma, at the gynecologic clinic of the university of G\u00f6ttingen and at the gynecologic and obstetric center at Giessen a peritoneography is made. If the distribution of the contrast solution is homogeneous within the abdomen, a homogeneous distribution of activity can also be expected after the radiogold instillation. By means of the peritoneography it is possible to see incorrect punctures into the abdominal walls, into the intestine, into the retroperitoneal space, or into peritoneal conglutinations before the radiogold instillation. Peritoneography, therefore, contributes to a reduction of the early complications of the radiogold therapy. The method used in peritoneography at G\u00f6ttingen and the method of Giessen are described. The first one (G\u00f6ttingen) is more comfortable for the patient, as it necessitates less changes of position; the other (Giessen) is a little more economical. A suitable cannula for puncture is described.", "contents": "[Experience in peritoneography, for the prevention of the primary complications during intraperitoneal instillation of radiogold]. Prior to intraabdominal radiogold therapy of the ovarian carcinoma, at the gynecologic clinic of the university of G\u00f6ttingen and at the gynecologic and obstetric center at Giessen a peritoneography is made. If the distribution of the contrast solution is homogeneous within the abdomen, a homogeneous distribution of activity can also be expected after the radiogold instillation. By means of the peritoneography it is possible to see incorrect punctures into the abdominal walls, into the intestine, into the retroperitoneal space, or into peritoneal conglutinations before the radiogold instillation. Peritoneography, therefore, contributes to a reduction of the early complications of the radiogold therapy. The method used in peritoneography at G\u00f6ttingen and the method of Giessen are described. The first one (G\u00f6ttingen) is more comfortable for the patient, as it necessitates less changes of position; the other (Giessen) is a little more economical. A suitable cannula for puncture is described."} {"id": "PMID:1258076", "title": "[Effect of x-rays on changes in electrolytes and metabolism of the myocardium. VI. Radiation-induced changes of catecholamine content].", "content": "In the myocardium of guinea-pigs, the behaviour of the catecholamines noradrenalin and adrenalin as well as the monoamine oxidase activity was biochemically studied following a local irradiation with 250 up to 6000 R surface dose. The noradrenalin content is significantly reduced already after a surface dose of 250 R. This drop of the noradrenalin content is beginning 15 min after irradiation, and not till 72 hours later, a complete normalization of the noradrenalin content is to be shown. A fractionated irradiation with twice 250 R SD in an interval of 24 hours leads to a further reduction. The changes of the adrenalin content are uncharacteristic, the activity of the monoamine oxidase is unaffected.", "contents": "[Effect of x-rays on changes in electrolytes and metabolism of the myocardium. VI. Radiation-induced changes of catecholamine content]. In the myocardium of guinea-pigs, the behaviour of the catecholamines noradrenalin and adrenalin as well as the monoamine oxidase activity was biochemically studied following a local irradiation with 250 up to 6000 R surface dose. The noradrenalin content is significantly reduced already after a surface dose of 250 R. This drop of the noradrenalin content is beginning 15 min after irradiation, and not till 72 hours later, a complete normalization of the noradrenalin content is to be shown. A fractionated irradiation with twice 250 R SD in an interval of 24 hours leads to a further reduction. The changes of the adrenalin content are uncharacteristic, the activity of the monoamine oxidase is unaffected."} {"id": "PMID:1258077", "title": "Radioprotection of liver lipids of whole-body gamma-irradiated female rats by cystamine.", "content": "The effect of administration of cystamine (5 mg/100 g body weight) before 1200 R whole-body gamma irradiation has been studied on irradiation-induced changes in liver and its subcellular fractions'lipids of fasted female rats. Cystamine prevented the irradiation-induced increase in liver triglycerides and liver mitochondrial total phospholipids, but it decreased microsomal total phospholipids and proteins. Cystamine prevented the radiation-induced increased 32P-radioactivity (counts/min/mumole phospholipid phosphorus) of microsomal phosphatidyl choline. Cystamine prevented the radiation-induced increased uptake of NaH232PO4 (counts/min/g liver) in liver microsomal phosphatidyl ethanolamine and supernatant phosphatidyl choline; but in microsomal phosphatidyl choline, cystamine did not do so, but on the other hand it itself increased the uptake in control rats. Cystamine did not prevent the irradiation-induced decreased incorporation of (U-14C)glucose into liver triglycerides, total phospholipids and phosphatidyl choline. Cystamine itself decreased the incorporation of (U-14C)glucose into liver triglycerides and phosphoglycerides of control rats.", "contents": "Radioprotection of liver lipids of whole-body gamma-irradiated female rats by cystamine. The effect of administration of cystamine (5 mg/100 g body weight) before 1200 R whole-body gamma irradiation has been studied on irradiation-induced changes in liver and its subcellular fractions'lipids of fasted female rats. Cystamine prevented the irradiation-induced increase in liver triglycerides and liver mitochondrial total phospholipids, but it decreased microsomal total phospholipids and proteins. Cystamine prevented the radiation-induced increased 32P-radioactivity (counts/min/mumole phospholipid phosphorus) of microsomal phosphatidyl choline. Cystamine prevented the radiation-induced increased uptake of NaH232PO4 (counts/min/g liver) in liver microsomal phosphatidyl ethanolamine and supernatant phosphatidyl choline; but in microsomal phosphatidyl choline, cystamine did not do so, but on the other hand it itself increased the uptake in control rats. Cystamine did not prevent the irradiation-induced decreased incorporation of (U-14C)glucose into liver triglycerides, total phospholipids and phosphatidyl choline. Cystamine itself decreased the incorporation of (U-14C)glucose into liver triglycerides and phosphoglycerides of control rats."} {"id": "PMID:1258078", "title": "Distribution and behavior of isoselenouronium salts in the body. V. Acute toxicity and metabolic fate of selenium derivatives.", "content": "The acute toxicity of AESe, 2-ASe, and Se-MEG was estimated in mice after i.v., i.p. and s.c. application. In all forms of application, 2-ASe was found to have the lowest toxicity. The study of excretion showed that administered compounds are excreted practically completely within seven days, mostly by urine. The excretion by faeces is very low and by exhalation is under the threshold of demonstrability. The metabolism of 2-ASe is slow, most of it is excreted without any change; AESe is transformed into a mixture of 2-ASe and Se-MEG. Se-MEG is excreted by urine totally metabolized as trimethylselenium ion.", "contents": "Distribution and behavior of isoselenouronium salts in the body. V. Acute toxicity and metabolic fate of selenium derivatives. The acute toxicity of AESe, 2-ASe, and Se-MEG was estimated in mice after i.v., i.p. and s.c. application. In all forms of application, 2-ASe was found to have the lowest toxicity. The study of excretion showed that administered compounds are excreted practically completely within seven days, mostly by urine. The excretion by faeces is very low and by exhalation is under the threshold of demonstrability. The metabolism of 2-ASe is slow, most of it is excreted without any change; AESe is transformed into a mixture of 2-ASe and Se-MEG. Se-MEG is excreted by urine totally metabolized as trimethylselenium ion."} {"id": "PMID:1258079", "title": "Distribution and behavior of isoselenouronium salts in the body. VI. Comparative study of distribution and radioprotectivity of selenium derivatives.", "content": "The protective effect of AESe, 2-ASe, and Se-MEG during irradiation with a dose rate of 500 R/min was followed. The protective effect of 2-ASe is substantially lower during the dose rate of 20 R/min and even during an increased dose. AESe and Se-MEG are noneffective. The time of duration of the protective effect of 2-ASe corresponds to the period of its high concentration in the organism after the administration, i.e. ca. 45 min.", "contents": "Distribution and behavior of isoselenouronium salts in the body. VI. Comparative study of distribution and radioprotectivity of selenium derivatives. The protective effect of AESe, 2-ASe, and Se-MEG during irradiation with a dose rate of 500 R/min was followed. The protective effect of 2-ASe is substantially lower during the dose rate of 20 R/min and even during an increased dose. AESe and Se-MEG are noneffective. The time of duration of the protective effect of 2-ASe corresponds to the period of its high concentration in the organism after the administration, i.e. ca. 45 min."} {"id": "PMID:1258081", "title": "[The irradiation of air-filled cavities in a plexiglass phantom using 42 MiV bremsstrahlung].", "content": "For the investigation of dose distributions as they are produced by the existence of cavities within the irradiated volume, a nonhomogeneous plexiglass phantom has been exposed to a 42 MeV radiation due to retarding of particles. Depth dose curves as well as the ion dose of the interface being more distant from the focus have been measured using different dimensions and depths of the cavity. The modifications of the dose distribution are essentially due to the density difference producing the displacement of the depth dose curve and to multiple scattering effects. The displacement of the depth dose curve amounts to about two thirds of that dimension of the cavity which runs parallel to the radiation axis. An increase or a decrease of the ionization within the air-filled volume results from multiple scattering effects and in dependent on the shape of the cavity.", "contents": "[The irradiation of air-filled cavities in a plexiglass phantom using 42 MiV bremsstrahlung]. For the investigation of dose distributions as they are produced by the existence of cavities within the irradiated volume, a nonhomogeneous plexiglass phantom has been exposed to a 42 MeV radiation due to retarding of particles. Depth dose curves as well as the ion dose of the interface being more distant from the focus have been measured using different dimensions and depths of the cavity. The modifications of the dose distribution are essentially due to the density difference producing the displacement of the depth dose curve and to multiple scattering effects. The displacement of the depth dose curve amounts to about two thirds of that dimension of the cavity which runs parallel to the radiation axis. An increase or a decrease of the ionization within the air-filled volume results from multiple scattering effects and in dependent on the shape of the cavity."} {"id": "PMID:1258080", "title": "Endogenous biochemical factors affecting the efficiency of some radioprotective or radiosensitizing drugs: sulfhydryl groups and lipid peroxides.", "content": "The changes in the amounts of blood and tissular sulfhydryl groups and lipid peroxides were investigated in lethally gamma-irradiated rats treated with cystamine, AET (radioprotectors) or alpha-methyl-dopa (a radiosensitizer). The results of experiments revealed the following findings: 1. The ionizing radiation generally causes increases in the levels of tissular sulfhydryl groups and lipid peroxides (excepting the hepatic levels of these compounds). 2. AET and, especially, cystamine are able to reverse the radiation-induced changes in the tissular amounts of sulfhydryl groups and lipid peroxides; there are close relationships between this effect (including its intensity and extension) and the radioprotective action of these drugs. 3. In spite of its radiosensitizing action, alpha-methyl-dopa induces approximately similar changes in the tissular amounts of sulfhydryl groups and lipid peroxides, suggesting that biochemical processes other than an excessive yield of free radicals are also involved in radiosensitivity.", "contents": "Endogenous biochemical factors affecting the efficiency of some radioprotective or radiosensitizing drugs: sulfhydryl groups and lipid peroxides. The changes in the amounts of blood and tissular sulfhydryl groups and lipid peroxides were investigated in lethally gamma-irradiated rats treated with cystamine, AET (radioprotectors) or alpha-methyl-dopa (a radiosensitizer). The results of experiments revealed the following findings: 1. The ionizing radiation generally causes increases in the levels of tissular sulfhydryl groups and lipid peroxides (excepting the hepatic levels of these compounds). 2. AET and, especially, cystamine are able to reverse the radiation-induced changes in the tissular amounts of sulfhydryl groups and lipid peroxides; there are close relationships between this effect (including its intensity and extension) and the radioprotective action of these drugs. 3. In spite of its radiosensitizing action, alpha-methyl-dopa induces approximately similar changes in the tissular amounts of sulfhydryl groups and lipid peroxides, suggesting that biochemical processes other than an excessive yield of free radicals are also involved in radiosensitivity."} {"id": "PMID:1258082", "title": "[Reproductive death and population kinetics of survived hamster cells in vitro during 48 hours following x-ray doses up to 800 Rad. II].", "content": "By means of a quantitative analysis, the time dependency of the number of dead cells and the resulting statement of cell numbers are compared with colony survival curves and with the distribution of colony sizes. The obtained periodical variation of reproductively killed cells is analyzed through population kinetics and is reduced to the number of those among the irradiated cells which show radiation-induced lethal reproductive damage. Therefrom, together with both sorts of interphase-dead cells, the dose dependency of the three lethal fractions results, taking into consideration the quantitative cellular statement. The formation of maxima of reproductively killed cells at the intervals of generation time until F3-generation is explained by an autosynchronization of partly lethally injured cell populations. From colony size distributions a linear dose dependency of the mean colony size group can be derived; this is discussed in connection with DNA double strand breaks regarded as a possible cause of reproductive lethal damages. The data obtained concerning the development of a cell population with radiation damages are evaluated by the construction of phylogenetic schedules for every 300 rd and 500 rd. By this means, the underlying population kinetics is being revised quantitatively.", "contents": "[Reproductive death and population kinetics of survived hamster cells in vitro during 48 hours following x-ray doses up to 800 Rad. II]. By means of a quantitative analysis, the time dependency of the number of dead cells and the resulting statement of cell numbers are compared with colony survival curves and with the distribution of colony sizes. The obtained periodical variation of reproductively killed cells is analyzed through population kinetics and is reduced to the number of those among the irradiated cells which show radiation-induced lethal reproductive damage. Therefrom, together with both sorts of interphase-dead cells, the dose dependency of the three lethal fractions results, taking into consideration the quantitative cellular statement. The formation of maxima of reproductively killed cells at the intervals of generation time until F3-generation is explained by an autosynchronization of partly lethally injured cell populations. From colony size distributions a linear dose dependency of the mean colony size group can be derived; this is discussed in connection with DNA double strand breaks regarded as a possible cause of reproductive lethal damages. The data obtained concerning the development of a cell population with radiation damages are evaluated by the construction of phylogenetic schedules for every 300 rd and 500 rd. By this means, the underlying population kinetics is being revised quantitatively."} {"id": "PMID:1258083", "title": "[Results of treatment for laryngeal carcinoma in W\u00fcrzburg].", "content": "From 1960 through 1972, altogether 418 patients with laryngeal carcinoma have been treated at W\u00fcrzburg, 333 = 82% of these by primary radiation therapy with Co-60 gamma-rays. The results are reported and analyzed in dependence on prognostic factors as tumor site and extension, formation of metastases and age of the patient. Five-year survival of primarily irradiated cases from 1960 to 1967; Glottic T1 = 90%, T2 = 70%, T3 -31%. Supraglottic T2 = 51%, T3 =20%, T4 = 16%. Quota of cases with posterior surgical treatment: Glottic = 8% supraglottic = 28%. The attempt to preserve the larnyx function by means of radiation therapy as an initial measure does not bring along any risk for the patient. The incidence of recurrences with secondary surgical treatment is not smaller than with irradiation only.", "contents": "[Results of treatment for laryngeal carcinoma in W\u00fcrzburg]. From 1960 through 1972, altogether 418 patients with laryngeal carcinoma have been treated at W\u00fcrzburg, 333 = 82% of these by primary radiation therapy with Co-60 gamma-rays. The results are reported and analyzed in dependence on prognostic factors as tumor site and extension, formation of metastases and age of the patient. Five-year survival of primarily irradiated cases from 1960 to 1967; Glottic T1 = 90%, T2 = 70%, T3 -31%. Supraglottic T2 = 51%, T3 =20%, T4 = 16%. Quota of cases with posterior surgical treatment: Glottic = 8% supraglottic = 28%. The attempt to preserve the larnyx function by means of radiation therapy as an initial measure does not bring along any risk for the patient. The incidence of recurrences with secondary surgical treatment is not smaller than with irradiation only."} {"id": "PMID:1258084", "title": "[Radiation therapy of eyelid carcinomas].", "content": "Forty patients with histologically verified tumors of the eyelid, partly being pretreated surgically, were irradiated and reexamined. The irradiations were performed with an apparatus for surface therapy using soft rays. The radiation quality was between 55 and 100 kV, the dose between 3000 and 6000 rd. The single doses amounted to 300 or 400 rd. The rate of recurrences after primary irradiation of basaliomas was 5,5%, the rate of recovery 94,5%. The patients who underwent primary operation show a distinctly increased rate of recurrences. The percentage of complications was small, amounting to 8%. Primary irradiation is recommended for the treatment of stages T1 and T2 of eyelid tumors, the percentage of recovery being high and the number of complications small. Advanced stages ought to be treated according to the site and infiltration of the tumor either by the telecaesium apparatus under conditions of semi-deep therapy with use of a lead satellite for protection of the cristalline lens and with following soft-ray therapy, or by primary operation followed by radiation therapy.", "contents": "[Radiation therapy of eyelid carcinomas]. Forty patients with histologically verified tumors of the eyelid, partly being pretreated surgically, were irradiated and reexamined. The irradiations were performed with an apparatus for surface therapy using soft rays. The radiation quality was between 55 and 100 kV, the dose between 3000 and 6000 rd. The single doses amounted to 300 or 400 rd. The rate of recurrences after primary irradiation of basaliomas was 5,5%, the rate of recovery 94,5%. The patients who underwent primary operation show a distinctly increased rate of recurrences. The percentage of complications was small, amounting to 8%. Primary irradiation is recommended for the treatment of stages T1 and T2 of eyelid tumors, the percentage of recovery being high and the number of complications small. Advanced stages ought to be treated according to the site and infiltration of the tumor either by the telecaesium apparatus under conditions of semi-deep therapy with use of a lead satellite for protection of the cristalline lens and with following soft-ray therapy, or by primary operation followed by radiation therapy."} {"id": "PMID:1258085", "title": "Effect of field size on the radiation penumbra and integral dose for telegamma therapy units.", "content": "Because of the large source size in telegamma therapy units, the boundaries of the radiation beam beyond the collimator are not well defined and a zone of falling dose and resulting penumbra are produced. In general, the collimator design is such that the geometrical penumbra is nearly equal in magnitude to the source diameter. However, the magnitude of the physical or radiation penumbra is influenced by the radiation transmitted through the edge of the collimator, the geometrical penumbra and the scatter from the source and the collimator. In the present study, the variation of radiation penumbra with field size has been investigated for two different makes of telegamma units. It is seen that the radiation penumbra can be as large as 4.8 cm for a 20 X 20 cm field. The effect of such large penumbra on the integral dose is discussed.", "contents": "Effect of field size on the radiation penumbra and integral dose for telegamma therapy units. Because of the large source size in telegamma therapy units, the boundaries of the radiation beam beyond the collimator are not well defined and a zone of falling dose and resulting penumbra are produced. In general, the collimator design is such that the geometrical penumbra is nearly equal in magnitude to the source diameter. However, the magnitude of the physical or radiation penumbra is influenced by the radiation transmitted through the edge of the collimator, the geometrical penumbra and the scatter from the source and the collimator. In the present study, the variation of radiation penumbra with field size has been investigated for two different makes of telegamma units. It is seen that the radiation penumbra can be as large as 4.8 cm for a 20 X 20 cm field. The effect of such large penumbra on the integral dose is discussed."} {"id": "PMID:1258086", "title": "Effect of gamma-irradiation on cholesterol of chicken brain.", "content": "Cholesterol in chicken brain has been determined after head irradiation with 60Co gamma rays. The brain of five-week-old white Leghorn chickens, irradiated with 1200 R showed appreciable decrease in its cholesterol content after two and five days, and a slight increase after seven days of irradiation. But the cholesterol content after seven days of irradiation was still less than the control values. However, an insignificant increase in brain cholesterol (than control) was observed after 14 days of irradiation. Nine to ten weeks old Rhode Island Red chickens exposed to 4000 R head gamma-irradiation exhibited a similar effect in cholesterol content of the brain.", "contents": "Effect of gamma-irradiation on cholesterol of chicken brain. Cholesterol in chicken brain has been determined after head irradiation with 60Co gamma rays. The brain of five-week-old white Leghorn chickens, irradiated with 1200 R showed appreciable decrease in its cholesterol content after two and five days, and a slight increase after seven days of irradiation. But the cholesterol content after seven days of irradiation was still less than the control values. However, an insignificant increase in brain cholesterol (than control) was observed after 14 days of irradiation. Nine to ten weeks old Rhode Island Red chickens exposed to 4000 R head gamma-irradiation exhibited a similar effect in cholesterol content of the brain."} {"id": "PMID:1258087", "title": "An estimate of the 60Co gamma attenuation in the small phantom enployed in the definition of tissue air ratio.", "content": "Tissue air ratio definition employs a concept of dose at the centre of a small mass of tissues that is suspended in air and is just large enough to give electronic equilibrium at its own centre. When the dose at the centre of the said small mass of tissue is to be derived from a knowledge of exposure in free air at the same point, the attenuation in the small mass of tissue should be taken into account. This attenuation for 1250 keV photons has been evaluated through a theroretical model and the attenuation factor is estimated to be 0.975.", "contents": "An estimate of the 60Co gamma attenuation in the small phantom enployed in the definition of tissue air ratio. Tissue air ratio definition employs a concept of dose at the centre of a small mass of tissues that is suspended in air and is just large enough to give electronic equilibrium at its own centre. When the dose at the centre of the said small mass of tissue is to be derived from a knowledge of exposure in free air at the same point, the attenuation in the small mass of tissue should be taken into account. This attenuation for 1250 keV photons has been evaluated through a theroretical model and the attenuation factor is estimated to be 0.975."} {"id": "PMID:1258088", "title": "[Critical consideration of various irradiation methods in Hodgkin's disease].", "content": "The utilization of individualized irradiation methods in Hodgkin's disease is reported. The advantages are emphasized in comparison with a schematized mantile therapy.", "contents": "[Critical consideration of various irradiation methods in Hodgkin's disease]. The utilization of individualized irradiation methods in Hodgkin's disease is reported. The advantages are emphasized in comparison with a schematized mantile therapy."} {"id": "PMID:1258089", "title": "[Development and utilization of the Nominal Standard Dose for the tolerance dosage to healthy tissue in radiotherapy].", "content": "The utilization of the Ellis-formula for the determination of the tolerance of normal connective tissue is described. Beyond this, the formula is adapted to so-called critical organs. The individual suppositions implicated by the Ellis-formula are commented. Because of the verifyable congruency of the Ellis-formula with data obtained in clinical practice also by other authors, this conception is presented for the provisional determination of the limits of tolerance of normal tissue together with a computerized programme elaborated for use in different therapeutic techniques.", "contents": "[Development and utilization of the Nominal Standard Dose for the tolerance dosage to healthy tissue in radiotherapy]. The utilization of the Ellis-formula for the determination of the tolerance of normal connective tissue is described. Beyond this, the formula is adapted to so-called critical organs. The individual suppositions implicated by the Ellis-formula are commented. Because of the verifyable congruency of the Ellis-formula with data obtained in clinical practice also by other authors, this conception is presented for the provisional determination of the limits of tolerance of normal tissue together with a computerized programme elaborated for use in different therapeutic techniques."} {"id": "PMID:1258090", "title": "[Improvement of gynecologic radium therapy through the afterloading method using cesium 137].", "content": "For all centers performing gynecological contact irradiation the use of afterloading techniques is urgently required, since they eliminate any radiation exposure to the personnel. The radio-therapist may position and control the empty applicators still free from radiation withoug haste. This procedure diminishes the occurrence of overdosages and underdosages. The care for the patients is possible without radiation exposure, and the morbidity of contact therapy can be reduced by occasional mobilization of the patient, the applicator without sources remaining at its place. The fully automatic apparatus \"Curietron\" using cesium-137 sources (0.662 MeV gamma emission, half-life period 26.6 years) with an equivalent source activity (factor 2.6) yields the dose distribution demanded in the gynecologic field which in practice is identical to that of Ra-226 (medium gamma emission 1 MeV, half-life period 1620 years). With similar dose distribution, a biological and therapeutical effect alike to Ra-226 may be expected from Cs-137. In comparison with Ra-226, the following advantages of Cs-137 may be mentioned: Lower half-value thickness of 5.5 mm lead (low expenses for radioprotection), less danger with handling (no emanation of radioactive gases), and lower contamination risks in case of breaking. The measured dose distributions at equivalent source activity and similar geometry of the applicators revealed the possibility with regard of all techniques of gynecologic irradiation utilized in our field of arriving at similar relative and absolute dose distributions by means of the Cs-137 afterloading technique. Whilst short-term afterloading irradiation with highly active sources, their radiobiological effectiveness being not yet ascertained, has to be tested at appropriate scientific centers, it is necessary to demand afterloading techniques with dosages and duration of irradiations approved over decades for all centers of gynecological contact therapy because of radiation protection.", "contents": "[Improvement of gynecologic radium therapy through the afterloading method using cesium 137]. For all centers performing gynecological contact irradiation the use of afterloading techniques is urgently required, since they eliminate any radiation exposure to the personnel. The radio-therapist may position and control the empty applicators still free from radiation withoug haste. This procedure diminishes the occurrence of overdosages and underdosages. The care for the patients is possible without radiation exposure, and the morbidity of contact therapy can be reduced by occasional mobilization of the patient, the applicator without sources remaining at its place. The fully automatic apparatus \"Curietron\" using cesium-137 sources (0.662 MeV gamma emission, half-life period 26.6 years) with an equivalent source activity (factor 2.6) yields the dose distribution demanded in the gynecologic field which in practice is identical to that of Ra-226 (medium gamma emission 1 MeV, half-life period 1620 years). With similar dose distribution, a biological and therapeutical effect alike to Ra-226 may be expected from Cs-137. In comparison with Ra-226, the following advantages of Cs-137 may be mentioned: Lower half-value thickness of 5.5 mm lead (low expenses for radioprotection), less danger with handling (no emanation of radioactive gases), and lower contamination risks in case of breaking. The measured dose distributions at equivalent source activity and similar geometry of the applicators revealed the possibility with regard of all techniques of gynecologic irradiation utilized in our field of arriving at similar relative and absolute dose distributions by means of the Cs-137 afterloading technique. Whilst short-term afterloading irradiation with highly active sources, their radiobiological effectiveness being not yet ascertained, has to be tested at appropriate scientific centers, it is necessary to demand afterloading techniques with dosages and duration of irradiations approved over decades for all centers of gynecological contact therapy because of radiation protection."} {"id": "PMID:1258091", "title": "[Radiotherapy of 4468 uterine carcinomas].", "content": "The treatment results of 3847 carcinomas of the cervix and of 621 carcinomas of the uterine corpus during a period from 1928 to 1966 are reported in a statistical review. The constancy of the absolute recovery rate of carcinomas comprising fifty per cent within all stages and different time intervals is supposed to be due to early standardization and multiple fractionation of the radiation therapy maintained without essential modifications. The recovery rate of carcinomas of the corpus was found amounting to 61 per cent altogether, remaining also unchanged, though, between cases with carcinomas solely irradiated (43%) and woman who were surgically treated before irradiation (87%) the difference of efficiency rates was increasing with the years.", "contents": "[Radiotherapy of 4468 uterine carcinomas]. The treatment results of 3847 carcinomas of the cervix and of 621 carcinomas of the uterine corpus during a period from 1928 to 1966 are reported in a statistical review. The constancy of the absolute recovery rate of carcinomas comprising fifty per cent within all stages and different time intervals is supposed to be due to early standardization and multiple fractionation of the radiation therapy maintained without essential modifications. The recovery rate of carcinomas of the corpus was found amounting to 61 per cent altogether, remaining also unchanged, though, between cases with carcinomas solely irradiated (43%) and woman who were surgically treated before irradiation (87%) the difference of efficiency rates was increasing with the years."} {"id": "PMID:1258092", "title": "[The influencing of rat-tail tumors with and without irradiation].", "content": "In a collective of 200 Wistar rats, the influence of anticoagulants upon the rat tail tumor (Walker 256 carcinosarcoma) was checked with and without irradiation. After implantation of the tumor and development of a certain definite tumor volume, the animals were divided into four different groups of 50 rats each. The first one was the control group without any manipulation, the second received an one-stage X-irradiation with 2500 R SD directed to the tail tumor, the third was treated with an oral dose of Phenprocoumon which was added to the daily drinking quantity (0.1 mg/kg body weight), and the fourth group was given an one-stage X-irradiation together with the oral Phenprocoumon treatment. The influence of these different treatments on the growth of the primary tumor, on the incidence of metastases and on the death rate was checked up. The best therapeutical effect was observed with combined radiation and Phenprocoumon treatment. The therapy resulted in an almost complete growth rate depression of the primary tumor, in an early tendency of remission of the primary tumor, a 42 per cent decrease of the incidence of metastases to the lung, and a 42 per cent increase of the survival rate. With regard to the frequency of metastases and to the survival rate, treatment with Phenprocoumon alone showed significantly better results as sole radiation treatment.", "contents": "[The influencing of rat-tail tumors with and without irradiation]. In a collective of 200 Wistar rats, the influence of anticoagulants upon the rat tail tumor (Walker 256 carcinosarcoma) was checked with and without irradiation. After implantation of the tumor and development of a certain definite tumor volume, the animals were divided into four different groups of 50 rats each. The first one was the control group without any manipulation, the second received an one-stage X-irradiation with 2500 R SD directed to the tail tumor, the third was treated with an oral dose of Phenprocoumon which was added to the daily drinking quantity (0.1 mg/kg body weight), and the fourth group was given an one-stage X-irradiation together with the oral Phenprocoumon treatment. The influence of these different treatments on the growth of the primary tumor, on the incidence of metastases and on the death rate was checked up. The best therapeutical effect was observed with combined radiation and Phenprocoumon treatment. The therapy resulted in an almost complete growth rate depression of the primary tumor, in an early tendency of remission of the primary tumor, a 42 per cent decrease of the incidence of metastases to the lung, and a 42 per cent increase of the survival rate. With regard to the frequency of metastases and to the survival rate, treatment with Phenprocoumon alone showed significantly better results as sole radiation treatment."} {"id": "PMID:1258093", "title": "Mechanisms underlying decreased protein and RNA synthesis in the rat spleen following whole-body X-irradiation.", "content": "Whole-body exposure of rats to 1000 R X-rays resulted in decreased rates in protein and RNA syntheses in the spleen from the fourth post-irradiation hour. These changes correspond well with impaired ability of nuclei to polymerise RNA, reduction in template efficiency of chromatin, decrease in the activity of RNA polymerase and inhibition in histone phosphorylation. Protection of the spleen by lead shielding during whole-body exposure to X-rays largely eliminated the observed alterations in protein and nucleic acid synthetic machineries. This suggests that the radiation-induced inhibition in protein and RNA syntheses is mainly due to the direct action of radiation on the spleen itself.", "contents": "Mechanisms underlying decreased protein and RNA synthesis in the rat spleen following whole-body X-irradiation. Whole-body exposure of rats to 1000 R X-rays resulted in decreased rates in protein and RNA syntheses in the spleen from the fourth post-irradiation hour. These changes correspond well with impaired ability of nuclei to polymerise RNA, reduction in template efficiency of chromatin, decrease in the activity of RNA polymerase and inhibition in histone phosphorylation. Protection of the spleen by lead shielding during whole-body exposure to X-rays largely eliminated the observed alterations in protein and nucleic acid synthetic machineries. This suggests that the radiation-induced inhibition in protein and RNA syntheses is mainly due to the direct action of radiation on the spleen itself."} {"id": "PMID:1258094", "title": "Microspectrophotometric quantitation of nucleic acid and protein in irradiated epidermis.", "content": "Nucleic acid and proteins of newborn rat tail subjected to local X-irradiation were microspectrophotometrically studied. Feulgen, gallocyanine chrom-alum and naphthol yellow S methods were performed for demonstration of DNA, total nucleic acid and proteins respectively. The amount of proteins and total nucleic acid increases concomitantly with reactional acanthosis. However, the proteins and nucleic acid decrease as from day 3 post-irradiation. A tentative interpretation of the results would point to a giantization of the epidermic cells not only caused by aqueous imbition but also by an actual increase of the cellular protoplasm.", "contents": "Microspectrophotometric quantitation of nucleic acid and protein in irradiated epidermis. Nucleic acid and proteins of newborn rat tail subjected to local X-irradiation were microspectrophotometrically studied. Feulgen, gallocyanine chrom-alum and naphthol yellow S methods were performed for demonstration of DNA, total nucleic acid and proteins respectively. The amount of proteins and total nucleic acid increases concomitantly with reactional acanthosis. However, the proteins and nucleic acid decrease as from day 3 post-irradiation. A tentative interpretation of the results would point to a giantization of the epidermic cells not only caused by aqueous imbition but also by an actual increase of the cellular protoplasm."} {"id": "PMID:1258095", "title": "[Initial results on the use of C11 recoil-labelled amino acids in the animal experiment].", "content": "Extracorporeal measurement of incorporated radioactive organic compounds needs labelling with gamma emitters. The elements of organic compounds have only very short-lived gamma-emitting isotopes. (Organic compounds, therefore, up to now were labelled by more or less stable chemical coupling with gamma-emitting isotopes of the halogens or of certain metals as, for instance, chromium-51). The use of the C-11 isotope with a half-life period of about 20 min, emitting gamma radiation due to the annihilation radiation of its positrons, is very problematical, because these very short-lived nuclides can be used only at the place of their production by nuclear engineering. But especially these nuclides are very interesting just because of their short half-life period, the radiation load being lessened thereby and, in addition, the organic compound remaining chemically unchanged. Utilizing the (gamma, n) reaction, we have succeeded in labelling organic molecules in solid state directly within the electron beam due to the retarding of particles from a linear electron accelerator, and the absolute as well as the specific yield was satisfying. Till now, we have tested almost exceptionally amino-acids; during experimentation with rats, an example of the practicable utilization in nuclear medicine was set by means of the amino-acid methionine. This was confirmed by results of comparative studies using C-14 and Se-75 labelled methionine (Se-methionine respectively).", "contents": "[Initial results on the use of C11 recoil-labelled amino acids in the animal experiment]. Extracorporeal measurement of incorporated radioactive organic compounds needs labelling with gamma emitters. The elements of organic compounds have only very short-lived gamma-emitting isotopes. (Organic compounds, therefore, up to now were labelled by more or less stable chemical coupling with gamma-emitting isotopes of the halogens or of certain metals as, for instance, chromium-51). The use of the C-11 isotope with a half-life period of about 20 min, emitting gamma radiation due to the annihilation radiation of its positrons, is very problematical, because these very short-lived nuclides can be used only at the place of their production by nuclear engineering. But especially these nuclides are very interesting just because of their short half-life period, the radiation load being lessened thereby and, in addition, the organic compound remaining chemically unchanged. Utilizing the (gamma, n) reaction, we have succeeded in labelling organic molecules in solid state directly within the electron beam due to the retarding of particles from a linear electron accelerator, and the absolute as well as the specific yield was satisfying. Till now, we have tested almost exceptionally amino-acids; during experimentation with rats, an example of the practicable utilization in nuclear medicine was set by means of the amino-acid methionine. This was confirmed by results of comparative studies using C-14 and Se-75 labelled methionine (Se-methionine respectively)."} {"id": "PMID:1258096", "title": "[Intraerythrocytic enzyme activities in euthyroid subjects and hyperthyroid patients before treatment and following stabilization of metabolism using radioiodine therapy].", "content": "The activities of six intra-erythrocytic enzymes--glucose-6-phosphate-dehydrogenase, aldolase, pyruvate kinase, hexokinase, triosephosphate-isomerase and phosphoglucomutase--have been measured in euthyroid probands (n=18) and in hyperthyroid patients (n=13) prior to radioiodine therapy and after stabilization of the metabolic conditions. The hexokinase, triosephosphate-isomerase, pyruvate kinase, and glucose-6-phosphate-dehydrogenase did not show any significant changes. A moderate diminution of the aldolase activity and a distinct decrease of the phosphoglucomutase activity occur during hyperthyroidism. After normalization of the metabolic conditions, both the enzymatic activities increase again.", "contents": "[Intraerythrocytic enzyme activities in euthyroid subjects and hyperthyroid patients before treatment and following stabilization of metabolism using radioiodine therapy]. The activities of six intra-erythrocytic enzymes--glucose-6-phosphate-dehydrogenase, aldolase, pyruvate kinase, hexokinase, triosephosphate-isomerase and phosphoglucomutase--have been measured in euthyroid probands (n=18) and in hyperthyroid patients (n=13) prior to radioiodine therapy and after stabilization of the metabolic conditions. The hexokinase, triosephosphate-isomerase, pyruvate kinase, and glucose-6-phosphate-dehydrogenase did not show any significant changes. A moderate diminution of the aldolase activity and a distinct decrease of the phosphoglucomutase activity occur during hyperthyroidism. After normalization of the metabolic conditions, both the enzymatic activities increase again."} {"id": "PMID:1258097", "title": "Effect of radiophosphorus on the developing endocrine glands of Swiss albino mice. I. A study on the thyroid gland.", "content": "A study has been made on the effects of P-32 on the developing thyroid gland of Swiss albino mice. The series of experiments reveal that: (I) P-32 at the dose rate of 1.0 muCi/g body-weight to the seven-day pregnant mouse has almost no effect on the 18-day foetus or as late as 14-day postnatal thyroid. (II) With the same dose, when given to one-day-old mouse, signs of dead mitotic figures are noticed. The effects are more pronounced in the beginning, but after the fourth week no morphological changes are seen. (III) When a seven-day-old animal is injected with the same dose, dead cells are found in the earlier stages followed by the damage to the vascular structure of the epithelium. (IV) The 14-day injected group shows damage to the epithelium in the form of condensed nuclei and loss of colloid from the follicles. Replacement of follicles by fatty degeneration is evident. (V) A maximum susceptibility to P-32 irradiation is shown by 21-day-old injected animals, where epithelial desquamation and replacement of follicles by fatty degeneration are easily marked one week after the injection. (VI) In the last group, where P-32 is given at the 28th day after parturition, there may be a tendency of the thickening of the blood vessels. (VII) The females show a greater damage to P-32 injection than the males in the postnatal period studied.", "contents": "Effect of radiophosphorus on the developing endocrine glands of Swiss albino mice. I. A study on the thyroid gland. A study has been made on the effects of P-32 on the developing thyroid gland of Swiss albino mice. The series of experiments reveal that: (I) P-32 at the dose rate of 1.0 muCi/g body-weight to the seven-day pregnant mouse has almost no effect on the 18-day foetus or as late as 14-day postnatal thyroid. (II) With the same dose, when given to one-day-old mouse, signs of dead mitotic figures are noticed. The effects are more pronounced in the beginning, but after the fourth week no morphological changes are seen. (III) When a seven-day-old animal is injected with the same dose, dead cells are found in the earlier stages followed by the damage to the vascular structure of the epithelium. (IV) The 14-day injected group shows damage to the epithelium in the form of condensed nuclei and loss of colloid from the follicles. Replacement of follicles by fatty degeneration is evident. (V) A maximum susceptibility to P-32 irradiation is shown by 21-day-old injected animals, where epithelial desquamation and replacement of follicles by fatty degeneration are easily marked one week after the injection. (VI) In the last group, where P-32 is given at the 28th day after parturition, there may be a tendency of the thickening of the blood vessels. (VII) The females show a greater damage to P-32 injection than the males in the postnatal period studied."} {"id": "PMID:1258098", "title": "Radioprotective effectiveness and toxicity of ATP, AET and serotonin applied individually or simultaneously to mice. II. Dose depending protection by single agents.", "content": "The work reported was done as a part of a detailed study on the antiradiation effects of three chemical agents-ATP, AET and serotonin-given individually or simultaneously, the ultimate aim being the identification of an optimally effective and non-toxic dose ratio for the triple combination of protectants. Individual PD50 (protectant dose ensuring 50% survival after lethal irradiation) values were found to be 166 mg/kg and 37 mg/kg for AET and serotonin, respectively. ATP was most effective (45% of 30-day-survival) at 1200 mg/kg in face of a level of X-irradiation above the minimum lethal dose. Some sex differences were observed in protection provided by everyone of the three agents, females being more susceptible to the protective action.", "contents": "Radioprotective effectiveness and toxicity of ATP, AET and serotonin applied individually or simultaneously to mice. II. Dose depending protection by single agents. The work reported was done as a part of a detailed study on the antiradiation effects of three chemical agents-ATP, AET and serotonin-given individually or simultaneously, the ultimate aim being the identification of an optimally effective and non-toxic dose ratio for the triple combination of protectants. Individual PD50 (protectant dose ensuring 50% survival after lethal irradiation) values were found to be 166 mg/kg and 37 mg/kg for AET and serotonin, respectively. ATP was most effective (45% of 30-day-survival) at 1200 mg/kg in face of a level of X-irradiation above the minimum lethal dose. Some sex differences were observed in protection provided by everyone of the three agents, females being more susceptible to the protective action."} {"id": "PMID:1258099", "title": "Influence of trichlorfon and fractionated irradiation on hydroproteolytic activity of pancreas and intestinal tissues of rats.", "content": "Investigations into the hydroproteolytic activity of pancreas and intestinal tissues (small intestine and colon) of rats after fractionated irradiation (5 X 150 R) were carried out. There was found marked postirradiation enhancement of lipase activity in pancreas and duodenal part of intestine and increase of B-glucuronidase and acid phosphatase activity in nearly all parts of the examined intestinal tissues. Fractionated irradiation resulted in an increase of pancreatic catheptic (proteolytic) activity causing simultaneous decrease of proteolytic activity in intestine and colon. Preventive administration of Trichlorfon (ten days before irradiation) in the dose of 10 mg or 30 mg/kg evoked modification of hydroproteolytic activity in intestinal tissues of healthy and irradiated rats. Trichlorfon applied in the dose of 30 mg/kg exerted antilipolytic and anticatheptic effects in pancreas and intestinal tissues of irradiated rats.", "contents": "Influence of trichlorfon and fractionated irradiation on hydroproteolytic activity of pancreas and intestinal tissues of rats. Investigations into the hydroproteolytic activity of pancreas and intestinal tissues (small intestine and colon) of rats after fractionated irradiation (5 X 150 R) were carried out. There was found marked postirradiation enhancement of lipase activity in pancreas and duodenal part of intestine and increase of B-glucuronidase and acid phosphatase activity in nearly all parts of the examined intestinal tissues. Fractionated irradiation resulted in an increase of pancreatic catheptic (proteolytic) activity causing simultaneous decrease of proteolytic activity in intestine and colon. Preventive administration of Trichlorfon (ten days before irradiation) in the dose of 10 mg or 30 mg/kg evoked modification of hydroproteolytic activity in intestinal tissues of healthy and irradiated rats. Trichlorfon applied in the dose of 30 mg/kg exerted antilipolytic and anticatheptic effects in pancreas and intestinal tissues of irradiated rats."} {"id": "PMID:1258100", "title": "Noninvasive diagnosis of carotid occlusion by ocular pneumoplethysmography.", "content": "An ocular pneumoplethysmograph was devised to measure the systolic pressure in the ophthalmic artery and to obtain calibrated pulse volume changes from the ocular globe, with simultaneous recording from both eyes. The instrument is self-contained and portable. It can be applied by paramedical personnel, and the graphic recording is readily interpreted by the physician. It has proved to be 100% accurate in noninvasively detecting unilateral carotid occlusion or preocclusive stenosis. This technique, when combined with carotid compression, has been shown to be most valuable in assessing the tolerance of a cerebral hemisphere to proximal carotid occlusion. It was used to evaluate a wide variety of carotid arterial lesions. Elective carotid resection without graft replacement and urgent and elective carotid ligations were performed, based on the preoperative prediction that such procedures would be tolerated without neurological injury. The instrument and the technique of its application are simple, safe, and accurate.", "contents": "Noninvasive diagnosis of carotid occlusion by ocular pneumoplethysmography. An ocular pneumoplethysmograph was devised to measure the systolic pressure in the ophthalmic artery and to obtain calibrated pulse volume changes from the ocular globe, with simultaneous recording from both eyes. The instrument is self-contained and portable. It can be applied by paramedical personnel, and the graphic recording is readily interpreted by the physician. It has proved to be 100% accurate in noninvasively detecting unilateral carotid occlusion or preocclusive stenosis. This technique, when combined with carotid compression, has been shown to be most valuable in assessing the tolerance of a cerebral hemisphere to proximal carotid occlusion. It was used to evaluate a wide variety of carotid arterial lesions. Elective carotid resection without graft replacement and urgent and elective carotid ligations were performed, based on the preoperative prediction that such procedures would be tolerated without neurological injury. The instrument and the technique of its application are simple, safe, and accurate."} {"id": "PMID:1258101", "title": "Alterations in behavior, brain electrical activity, cerebral blood flow, and intracranial pressure produced by triethyl tin sulfate induced cerebral edema.", "content": "The interrelationships between cerebral edema, intracranial pressure (ICP), and cerebral blood flow (CBF) were studied in acute and chronic triethyl tin sulfate treated rats. Prior to pentobarbital anesthesia behavioral observations were made. ICP and regional CBF were measured under steady state conditions and brain water content was determined by vacuum drying of the right cerebral hemisphere. Control and chronic animals were neurologically normal. There were two distinct acute groups: (1) acute low pressure (ALP) animals - alert but tetraperetic, and (2) acute high pressure (AHP) animals - deeply stuporous, with minimal pain response and gross EEG slowing. ICP was significantly elevated only in AHP animals. Hemispheric CBF was significantly reduced in AHP and chronic animals. The interaction of increased pressure and edema (AHP) produced the greatest decrease in CBF, although deep white flows were significantly affected in all experimental groups. Chronic animals had significantly lower flow in four of seven regions compared to ALP animals despite no significant difference in ICP. Water content was significantly increased in all experimental groups with the greatest increase in the chronic animals. In the absence of any significant increase in ICP, cerebral edema appears to cause a significant reduction in cerebral blood flow and this reduction corresponds with the magnitude and location of the edema.", "contents": "Alterations in behavior, brain electrical activity, cerebral blood flow, and intracranial pressure produced by triethyl tin sulfate induced cerebral edema. The interrelationships between cerebral edema, intracranial pressure (ICP), and cerebral blood flow (CBF) were studied in acute and chronic triethyl tin sulfate treated rats. Prior to pentobarbital anesthesia behavioral observations were made. ICP and regional CBF were measured under steady state conditions and brain water content was determined by vacuum drying of the right cerebral hemisphere. Control and chronic animals were neurologically normal. There were two distinct acute groups: (1) acute low pressure (ALP) animals - alert but tetraperetic, and (2) acute high pressure (AHP) animals - deeply stuporous, with minimal pain response and gross EEG slowing. ICP was significantly elevated only in AHP animals. Hemispheric CBF was significantly reduced in AHP and chronic animals. The interaction of increased pressure and edema (AHP) produced the greatest decrease in CBF, although deep white flows were significantly affected in all experimental groups. Chronic animals had significantly lower flow in four of seven regions compared to ALP animals despite no significant difference in ICP. Water content was significantly increased in all experimental groups with the greatest increase in the chronic animals. In the absence of any significant increase in ICP, cerebral edema appears to cause a significant reduction in cerebral blood flow and this reduction corresponds with the magnitude and location of the edema."} {"id": "PMID:1258102", "title": "Surgical treatment of primary intracerebral hemorrhage- Part 1: new angiographical classification.", "content": "A new angiographical classification of primary intracerebral hemorrhage is presented. We have clarified the predilection sites of intracerebral hemorrhage and the advancing direction of the hematoma by studying autopsy cases. Furthermore, we tried to detect the presence or absence of destruction of the internal capsule and ventricular rupture by means of angiography. Our classification, introducing the idea of dynamic changes of hematoma advancement from localized to advanced type, can be applied to clinical practice. This classification, along with the patient's level of consciousness, it felt to be the most important indication for operation.", "contents": "Surgical treatment of primary intracerebral hemorrhage- Part 1: new angiographical classification. A new angiographical classification of primary intracerebral hemorrhage is presented. We have clarified the predilection sites of intracerebral hemorrhage and the advancing direction of the hematoma by studying autopsy cases. Furthermore, we tried to detect the presence or absence of destruction of the internal capsule and ventricular rupture by means of angiography. Our classification, introducing the idea of dynamic changes of hematoma advancement from localized to advanced type, can be applied to clinical practice. This classification, along with the patient's level of consciousness, it felt to be the most important indication for operation."} {"id": "PMID:1258103", "title": "Geographic differences in mortality from stroke in North Caroline. 1. Analysis of death certificates.", "content": "Analysis of death certification in North Carolina for a three-year period, 1969 through 1971, showed regional differences in mortality rates from stroke in white men, with the highest rates in the Plains (tobacco growing and farming) area and the lowest rates in the Mountain region. These geographic differences in death rates were observed in all but the youngest age decade and also in the various types of stroke, i.e., hemorrhagic and occlusive cerebrovascular diseases. This regional variation in mortality, however, was not present in white women or blacks. The prevalence at death of heart disease, hypertension and diabetes also was higher in the Plains than in the Mountain region, suggesting that the observed geographic variation of stroke mortality is related to one or more of these major risk factors. It is concluded that the geographic differences in stroke mortality, which had been reported during previous decades, are real and are not due to variations in death certification, errors in diagnosis, or other explanations that might artificially produce inaccuracies in vital statistics.", "contents": "Geographic differences in mortality from stroke in North Caroline. 1. Analysis of death certificates. Analysis of death certification in North Carolina for a three-year period, 1969 through 1971, showed regional differences in mortality rates from stroke in white men, with the highest rates in the Plains (tobacco growing and farming) area and the lowest rates in the Mountain region. These geographic differences in death rates were observed in all but the youngest age decade and also in the various types of stroke, i.e., hemorrhagic and occlusive cerebrovascular diseases. This regional variation in mortality, however, was not present in white women or blacks. The prevalence at death of heart disease, hypertension and diabetes also was higher in the Plains than in the Mountain region, suggesting that the observed geographic variation of stroke mortality is related to one or more of these major risk factors. It is concluded that the geographic differences in stroke mortality, which had been reported during previous decades, are real and are not due to variations in death certification, errors in diagnosis, or other explanations that might artificially produce inaccuracies in vital statistics."} {"id": "PMID:1258105", "title": "Cerebral infarction following bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats: a pathological study.", "content": "A pathological examination was performed on normotensive rats (NTR) and spontaneously hypertensive rats (SHR) following bilateral common carotid artery ligation. After ligation, diffuse and extensive cerebral infarcts in the carotid artery territory occurred frequently in SHR, while NTR occasionally had well-circumscribed small infarcts. The posterior communicating arteries, which are the major anastomotic channels connecting the carotid and vertebrobasilar systems, did not show any anomalies and were well developed in SHR and NTR. Vascular changes secondary to hypertension, such as fibrinoid necrosis or thickening of the wall, were not observed in SHR. Because of the paucity of structural difference of the blood vessels, the more diffuse and extensive cerebral infarcts in SHR after carotid occlusion were attributed to the hemodynamic difference rather than the morphological difference between the two groups. The results of the present experiment suggest that hypertension per se, i.e., hemodynamic factors, may be operative for the development of cerebral infarction.", "contents": "Cerebral infarction following bilateral carotid artery ligation in normotensive and spontaneously hypertensive rats: a pathological study. A pathological examination was performed on normotensive rats (NTR) and spontaneously hypertensive rats (SHR) following bilateral common carotid artery ligation. After ligation, diffuse and extensive cerebral infarcts in the carotid artery territory occurred frequently in SHR, while NTR occasionally had well-circumscribed small infarcts. The posterior communicating arteries, which are the major anastomotic channels connecting the carotid and vertebrobasilar systems, did not show any anomalies and were well developed in SHR and NTR. Vascular changes secondary to hypertension, such as fibrinoid necrosis or thickening of the wall, were not observed in SHR. Because of the paucity of structural difference of the blood vessels, the more diffuse and extensive cerebral infarcts in SHR after carotid occlusion were attributed to the hemodynamic difference rather than the morphological difference between the two groups. The results of the present experiment suggest that hypertension per se, i.e., hemodynamic factors, may be operative for the development of cerebral infarction."} {"id": "PMID:1258106", "title": "Platelet survival studies in stroke-prone spontaneously hypertensive rats (SHRSP).", "content": "Platelet survival was studied by using 51Cr-labeled platelets in stroke-prone spontaneously hypertensive rats (SHRSP), stroke-resistant SHR (SHRSR) and normotensive control rats of the Wistar-Kyoto (WK) strain. Relatively young animals of the same age prior to the development of cerebrovascular lesions (cerebral infarction and/or hemorrhage) were used. Platelet half-life time in SHRSP was slightly but significantly shorter than in any other groups or rats, irrespective of the type of platelet donors. Mean platelet consumption was also significantly increased in SHRSP only. Platelets of SHRSP injected into SHRSR showed normal survival. These data support the concept that the shortened platelet survival in SHRSP is brought about by some extracorpuscular abnormalities. Although the vascular changes in SHRSP could be the most likely explanation for the shortened platelet survival, its mechanism remains to be solved. This investigation suggests that studies of the platelet survival in hypertension may be useful in predicting the development of stroke before its clinical recognition.", "contents": "Platelet survival studies in stroke-prone spontaneously hypertensive rats (SHRSP). Platelet survival was studied by using 51Cr-labeled platelets in stroke-prone spontaneously hypertensive rats (SHRSP), stroke-resistant SHR (SHRSR) and normotensive control rats of the Wistar-Kyoto (WK) strain. Relatively young animals of the same age prior to the development of cerebrovascular lesions (cerebral infarction and/or hemorrhage) were used. Platelet half-life time in SHRSP was slightly but significantly shorter than in any other groups or rats, irrespective of the type of platelet donors. Mean platelet consumption was also significantly increased in SHRSP only. Platelets of SHRSP injected into SHRSR showed normal survival. These data support the concept that the shortened platelet survival in SHRSP is brought about by some extracorpuscular abnormalities. Although the vascular changes in SHRSP could be the most likely explanation for the shortened platelet survival, its mechanism remains to be solved. This investigation suggests that studies of the platelet survival in hypertension may be useful in predicting the development of stroke before its clinical recognition."} {"id": "PMID:1258108", "title": "The role of the carotid body in mediating the cerebrovascular response to altered arterial carbon dioxide tension.", "content": "The role of the carotid bifurcation chemoreceptors in mediating the cerebrovascular response to altered arterial PCO2 has been suggested to be large. In the present study the cerebrovascular response to raised PCO2 was measured in a group of baboons before and after bilateral inactivation of the carotid bodies. The results suggest that these chemoreceptors do play a part in the cerebral vasodilator response to raised PCO2. The role of the carotid body, however, appears to be relatively minor as it only accounted for +/- 40% of the total response and became significant only at arterial PCO2 levels of more than 50 mm Hg. It is postulated that the peripheral chemoreceptors in the carotid bifurcation mediate part of the cerebrovascular response to altered PaCO2 but the role is quantitatively small.", "contents": "The role of the carotid body in mediating the cerebrovascular response to altered arterial carbon dioxide tension. The role of the carotid bifurcation chemoreceptors in mediating the cerebrovascular response to altered arterial PCO2 has been suggested to be large. In the present study the cerebrovascular response to raised PCO2 was measured in a group of baboons before and after bilateral inactivation of the carotid bodies. The results suggest that these chemoreceptors do play a part in the cerebral vasodilator response to raised PCO2. The role of the carotid body, however, appears to be relatively minor as it only accounted for +/- 40% of the total response and became significant only at arterial PCO2 levels of more than 50 mm Hg. It is postulated that the peripheral chemoreceptors in the carotid bifurcation mediate part of the cerebrovascular response to altered PaCO2 but the role is quantitatively small."} {"id": "PMID:1258104", "title": "Pathogenetic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans.", "content": "The predilection sites of cerebrovascular lesions (cerebral hemorrhage and/or softening) were studied in 1,278 stroke-prone spontaneously hypertensive rats (SHRSP). The precise supply to the main cerebral arteries was determined by trypan blue injections and microangiography. The three major territories were the anteromedial cortex, the occipital cortex, and the basal ganglia. A common angioarchitectural characteristic of these three areas was the blood supply through \"recurrent branching\" from the main stream. In the basal ganglia, where there is a preponderance of lesions, the arteries responsible for these lesions belonged to the lateral group of lenticulostriate arteries. The primary pre-stroke arterial lesions were further studied microangiographically in SHRSP killed at the time the initial symptoms of stroke were detected. These points were located at the \"boundary zone\" of the main cerebral arteries. Our findings indicated the importance of these two angioarchitectural minor loci as the basis for functional or organic circulatory disturbances that may cause stroke. Since these local factors of stroke are common in the cortex and basal ganglia of rats and basal ganglia of humans, these SHRSP are regarded as good pathogenetic models for studies on stroke in humans.", "contents": "Pathogenetic similarity of strokes in stroke-prone spontaneously hypertensive rats and humans. The predilection sites of cerebrovascular lesions (cerebral hemorrhage and/or softening) were studied in 1,278 stroke-prone spontaneously hypertensive rats (SHRSP). The precise supply to the main cerebral arteries was determined by trypan blue injections and microangiography. The three major territories were the anteromedial cortex, the occipital cortex, and the basal ganglia. A common angioarchitectural characteristic of these three areas was the blood supply through \"recurrent branching\" from the main stream. In the basal ganglia, where there is a preponderance of lesions, the arteries responsible for these lesions belonged to the lateral group of lenticulostriate arteries. The primary pre-stroke arterial lesions were further studied microangiographically in SHRSP killed at the time the initial symptoms of stroke were detected. These points were located at the \"boundary zone\" of the main cerebral arteries. Our findings indicated the importance of these two angioarchitectural minor loci as the basis for functional or organic circulatory disturbances that may cause stroke. Since these local factors of stroke are common in the cortex and basal ganglia of rats and basal ganglia of humans, these SHRSP are regarded as good pathogenetic models for studies on stroke in humans."} {"id": "PMID:1258110", "title": "Cerebral manifestations of ergotism. Report of a case and review of the literature.", "content": "A patient with diffuse and focal cerebral dysfunction was found to have absent peripheral pulses. Cerbral angiography revealed evidence of an arteritis with bilateral high grade carotid stenosis. When there was no laboratory confirmation of the arteritis, an iatrogenic etiology (ergotism) was suspected. This was later confirmed by the patient. The pertinent literature on ergotism is reviewed, and it is emphasized that ergotism may develop in patients on therapeutic doses of the drug.", "contents": "Cerebral manifestations of ergotism. Report of a case and review of the literature. A patient with diffuse and focal cerebral dysfunction was found to have absent peripheral pulses. Cerbral angiography revealed evidence of an arteritis with bilateral high grade carotid stenosis. When there was no laboratory confirmation of the arteritis, an iatrogenic etiology (ergotism) was suspected. This was later confirmed by the patient. The pertinent literature on ergotism is reviewed, and it is emphasized that ergotism may develop in patients on therapeutic doses of the drug."} {"id": "PMID:1258109", "title": "Fate of stroke patients transferred to a long-term rehabilitation hospital.", "content": "The rehabilitation outcome of 25 elderly hemiplegic patients discharged from the rehabilitation facilities of an acute general hospital and admitted to a long-term facility hospital was evaluated. Only those patients who had been on a rehabilitation program and were discharged after an average of 11 weeks because of lack of progress or severity of their functional and/or neurological disability were considered for this study. Twenty-two patients were wheelchair bound on admission and severely dependent in most self-care activities. Improvement in function and performance occurred in ten patients, while 13 patients remained unchanged. Among the improved patients, eight became ambulatory and independent in activities of daily living (ADL), eight became independent from a wheel-chair level, and eight returned home or to the community. The average stay of the patients in the chronic rehabilitation care facility was seven months, although all the patients reached their maximum level of performance within six months. It appears from this study that some hemiplegic patients require a long and intensive rehabilitation program.", "contents": "Fate of stroke patients transferred to a long-term rehabilitation hospital. The rehabilitation outcome of 25 elderly hemiplegic patients discharged from the rehabilitation facilities of an acute general hospital and admitted to a long-term facility hospital was evaluated. Only those patients who had been on a rehabilitation program and were discharged after an average of 11 weeks because of lack of progress or severity of their functional and/or neurological disability were considered for this study. Twenty-two patients were wheelchair bound on admission and severely dependent in most self-care activities. Improvement in function and performance occurred in ten patients, while 13 patients remained unchanged. Among the improved patients, eight became ambulatory and independent in activities of daily living (ADL), eight became independent from a wheel-chair level, and eight returned home or to the community. The average stay of the patients in the chronic rehabilitation care facility was seven months, although all the patients reached their maximum level of performance within six months. It appears from this study that some hemiplegic patients require a long and intensive rehabilitation program."} {"id": "PMID:1258107", "title": "Temporal profile (clinical course) of acute carotid system cerebral infarction.", "content": "The records of 179 consecutive patients with acute carotid system cerebral infarction were studied to describe the temporal profile of the clinical events during the first week of the illness. Only those patients admitted to the cerebrovascular hospital service within 36 hours of the onset of the first symptom were included. The neurological status of 39% was stable (unchanged) at the end of seven days; 35% of the patients gradually improved. Nineteen percent had a progressing neurological deficit from the onset which stabilized within 48 hours of onset. Six patients (3%) had a remitting-relapsing course during the first 36 hours. Eight patients (4%) had a significant late worsening, after 48 hours of stable or improving course. Mortality was 11% for the entire group. However, a high risk of death group was identified - the mortality was 41% for those patients who had any degree of decreased level of consciousness and hemiplegia at the time of admission.", "contents": "Temporal profile (clinical course) of acute carotid system cerebral infarction. The records of 179 consecutive patients with acute carotid system cerebral infarction were studied to describe the temporal profile of the clinical events during the first week of the illness. Only those patients admitted to the cerebrovascular hospital service within 36 hours of the onset of the first symptom were included. The neurological status of 39% was stable (unchanged) at the end of seven days; 35% of the patients gradually improved. Nineteen percent had a progressing neurological deficit from the onset which stabilized within 48 hours of onset. Six patients (3%) had a remitting-relapsing course during the first 36 hours. Eight patients (4%) had a significant late worsening, after 48 hours of stable or improving course. Mortality was 11% for the entire group. However, a high risk of death group was identified - the mortality was 41% for those patients who had any degree of decreased level of consciousness and hemiplegia at the time of admission."} {"id": "PMID:1258111", "title": "Distribution of progesterone and its effect on human blood during storage.", "content": "Human blood, drawn into ACD, was stored under blood bank conditions with and without addition of tritium-labeled progesterone. At selected storage intervals, several biochemical and biophysical parameters were assayed and the distribution of the hormone between plasma and erythrocytes was determined. The retention of the radioactive material by erythrocytes was studied by repeated washes and isotonic saline. The results indicate that erythrocytes stored with addition of progesterone have higher ATP levels, less spontaneous lysis, higher osmotic resistance, and higher uptake of methylene blue throughout the time of storage than do cells stored without added progesterone. This hormone appears to be in steady-state equilibrium between plasma and red blood cells during 42 days of storage and the amount in the plasma is almost twice that present in the cells. After repeated saline washes, about 10 er cent of the progesterone remains attached to the erythrocytes. Specific association of progesterone with red blood cell populations of different density shows that high specific activity is obtained in cell populations of low density (young cells) throughout the storage time investigated.", "contents": "Distribution of progesterone and its effect on human blood during storage. Human blood, drawn into ACD, was stored under blood bank conditions with and without addition of tritium-labeled progesterone. At selected storage intervals, several biochemical and biophysical parameters were assayed and the distribution of the hormone between plasma and erythrocytes was determined. The retention of the radioactive material by erythrocytes was studied by repeated washes and isotonic saline. The results indicate that erythrocytes stored with addition of progesterone have higher ATP levels, less spontaneous lysis, higher osmotic resistance, and higher uptake of methylene blue throughout the time of storage than do cells stored without added progesterone. This hormone appears to be in steady-state equilibrium between plasma and red blood cells during 42 days of storage and the amount in the plasma is almost twice that present in the cells. After repeated saline washes, about 10 er cent of the progesterone remains attached to the erythrocytes. Specific association of progesterone with red blood cell populations of different density shows that high specific activity is obtained in cell populations of low density (young cells) throughout the storage time investigated."} {"id": "PMID:1258112", "title": "Studies of the recovery and the cost of low-glycerol cryopreserved human red blood cells.", "content": "Red blood cells were equilibrated with 28 per cent (v/v) glycerol and 3 per cent mannitol in 0.65 g/100 ml sodium chloride. The units were frozen by immersion into liquid nitrogen and stored at -160 C. After thawing, they were reconstituted and washed using the IBM 2991 Blood Cell Processor. Freeze-thaw rate curves, the effect of thawing techniques, the effect of varying postthaw washing and processing techniques, estimates of red blood cell losses because of hemolysis, and in vitro recovery were determined. In vivo recovery was determined by 51Cr techniques 24 hours after infusion and Ashby survivals and subsequent life span were measured. Metabolic, scanning electronmicroscopy, cost estimates and quality control studies were done on the reconsituted red blood cells. Recipients were evaluated before and after transfusion for metabolic erythrocyte characteristics and for evidence of hemolysis. The modified method requires less wash solution and less technician time than does the standard low-glycerol method. Two units for the same recipient could be passed through the IBM software with no alteration of cell survival or loss. Revision of the IBM 2991 processing procedure provided excellent recovery of viable previously frozen red blood cells at probably a lower cost.", "contents": "Studies of the recovery and the cost of low-glycerol cryopreserved human red blood cells. Red blood cells were equilibrated with 28 per cent (v/v) glycerol and 3 per cent mannitol in 0.65 g/100 ml sodium chloride. The units were frozen by immersion into liquid nitrogen and stored at -160 C. After thawing, they were reconstituted and washed using the IBM 2991 Blood Cell Processor. Freeze-thaw rate curves, the effect of thawing techniques, the effect of varying postthaw washing and processing techniques, estimates of red blood cell losses because of hemolysis, and in vitro recovery were determined. In vivo recovery was determined by 51Cr techniques 24 hours after infusion and Ashby survivals and subsequent life span were measured. Metabolic, scanning electronmicroscopy, cost estimates and quality control studies were done on the reconsituted red blood cells. Recipients were evaluated before and after transfusion for metabolic erythrocyte characteristics and for evidence of hemolysis. The modified method requires less wash solution and less technician time than does the standard low-glycerol method. Two units for the same recipient could be passed through the IBM software with no alteration of cell survival or loss. Revision of the IBM 2991 processing procedure provided excellent recovery of viable previously frozen red blood cells at probably a lower cost."} {"id": "PMID:1258113", "title": "Exchange transfusion in Reye's syndrome with saline-washed red blood cells.", "content": "Reye's syndrome (RS) consists of encephalopathy, fatty degeneration of viscera, and elevation of ammonia, certain amino acids, and liver enzymes in the blood. It is most characteristically a disease of children and has been considered to have a poor prognosis despite the use of various treatment regimens. Exchange transfusion (ET) with fresh blood (less than 24 hours old) for the removal of toxic metabolic byproducts in TS is a relatively recent development which appears to have improved the survival rates. However, because RS may occur in epidemic proportions at any time the demand for fresh blood can place an excessive stress on blood resources. We have, therefore, utilized saline-washed (to remove potentially toxic metabolites) red blood cells (RBC's) less than six days old, and fresh frozen citrate-phosphate-dextrose (CPD) plasma in treating this disorder. Nine patients in the Milwaukee community with severe encephalopathy secondary to RS were treated with ET. These patients collectively required 151 units of washed RBC's for 21 ET. Eight of nine patients survived without sequelae. Age of blood used did not correlate with the number of exchanges required or the eventual outcome. A continual computerized EEG in five patients provided objective evidence of the effectiveness of ET. We conclude that ET with saline-washed RBC's reconstituted with fresh frozen plasma (FFP) is a fast, safe, and effective means of treating patients with RS.", "contents": "Exchange transfusion in Reye's syndrome with saline-washed red blood cells. Reye's syndrome (RS) consists of encephalopathy, fatty degeneration of viscera, and elevation of ammonia, certain amino acids, and liver enzymes in the blood. It is most characteristically a disease of children and has been considered to have a poor prognosis despite the use of various treatment regimens. Exchange transfusion (ET) with fresh blood (less than 24 hours old) for the removal of toxic metabolic byproducts in TS is a relatively recent development which appears to have improved the survival rates. However, because RS may occur in epidemic proportions at any time the demand for fresh blood can place an excessive stress on blood resources. We have, therefore, utilized saline-washed (to remove potentially toxic metabolites) red blood cells (RBC's) less than six days old, and fresh frozen citrate-phosphate-dextrose (CPD) plasma in treating this disorder. Nine patients in the Milwaukee community with severe encephalopathy secondary to RS were treated with ET. These patients collectively required 151 units of washed RBC's for 21 ET. Eight of nine patients survived without sequelae. Age of blood used did not correlate with the number of exchanges required or the eventual outcome. A continual computerized EEG in five patients provided objective evidence of the effectiveness of ET. We conclude that ET with saline-washed RBC's reconstituted with fresh frozen plasma (FFP) is a fast, safe, and effective means of treating patients with RS."} {"id": "PMID:1258114", "title": "Fatal pulmonary hypersensitivity reaction to HL-A incompatible blood transfusion:report of a case and review of the literature.", "content": "A girl with Thalassemia major reacted to a transfusion of packed red blood cells with increasing respiratory distress until death 12 1/2 hours later. Chills and fever were followed by dry cough, dyspnea, and pulmonary edema. The recipient had lymphocytotoxic antibodies specific for donor leukocyte antigens HL-A11 and possibly W14. At autopsy, the lungs showed pulmonary edema with extensive nonspecific acute alveolar injury. Similar cases in the literature are reviewed.", "contents": "Fatal pulmonary hypersensitivity reaction to HL-A incompatible blood transfusion:report of a case and review of the literature. A girl with Thalassemia major reacted to a transfusion of packed red blood cells with increasing respiratory distress until death 12 1/2 hours later. Chills and fever were followed by dry cough, dyspnea, and pulmonary edema. The recipient had lymphocytotoxic antibodies specific for donor leukocyte antigens HL-A11 and possibly W14. At autopsy, the lungs showed pulmonary edema with extensive nonspecific acute alveolar injury. Similar cases in the literature are reviewed."} {"id": "PMID:1258115", "title": "Hepatitis B virus and hepatitis B surface antigen in human albumin products.", "content": "A collection of 1,985 lots of normal serum albumin (NSA) and 1,361 lots of plasma protein fraction (PPF) prepared between 1958 and 1974 were tested for the presence of hepatitis B surface antigen (HBsAg). Twenty-one percent of NSA lots and 71 per cent of PPF lots were HBsAg-positive by radioimmunoassay. There was considerable variation in frequency of HBsAg-positive lots among the 17 different manufacturers of NSA and the six manufacturers of PPF. In general, those lots prepared from volunteer donor plasma and placental material demonstrated lower rates of HBsAg-positivity than those prepared from commercial donor plasma. A striking decrease in the prevalence of HBsAg-positive lots of both NSA and PPF occurred during the period 1971 to 1973, coincident with the onset of routine screening of all plasma for HBsAg. Although NSA and PPF can be HBsAg-positive, they probably do not transmit type B hepatitis. Serologic tests for HBsAg and antibody to HBsAg revealed that albumin products prepared from infectious, icterogenic plasma were infectious prior to pasteurization, but that they no longer transmitted type B hepatitis after heat treatment at 60 C for ten hours.", "contents": "Hepatitis B virus and hepatitis B surface antigen in human albumin products. A collection of 1,985 lots of normal serum albumin (NSA) and 1,361 lots of plasma protein fraction (PPF) prepared between 1958 and 1974 were tested for the presence of hepatitis B surface antigen (HBsAg). Twenty-one percent of NSA lots and 71 per cent of PPF lots were HBsAg-positive by radioimmunoassay. There was considerable variation in frequency of HBsAg-positive lots among the 17 different manufacturers of NSA and the six manufacturers of PPF. In general, those lots prepared from volunteer donor plasma and placental material demonstrated lower rates of HBsAg-positivity than those prepared from commercial donor plasma. A striking decrease in the prevalence of HBsAg-positive lots of both NSA and PPF occurred during the period 1971 to 1973, coincident with the onset of routine screening of all plasma for HBsAg. Although NSA and PPF can be HBsAg-positive, they probably do not transmit type B hepatitis. Serologic tests for HBsAg and antibody to HBsAg revealed that albumin products prepared from infectious, icterogenic plasma were infectious prior to pasteurization, but that they no longer transmitted type B hepatitis after heat treatment at 60 C for ten hours."} {"id": "PMID:1258117", "title": "Plasmapheresis-induced hemodilution and its effects on serum constituents.", "content": "Samples were obtained from 23 plasmapheresis donors before, during, and after double plasmapheresis. Seventeen chemical analyses were performed on these specimens and the results were subjected to statistical analysis. Representative samples can be obtained from plasmapheresis donors before the procedure has begun, immediately after the first unit of whole blood has been removed, or 15 minutes after the completion of the entire procedure. The sample obtained after the first unit of whole blood has been removed will show dilutional lowering of the uric acid concentration and the 15-minute equilibration sample will show dilutional lowering of the inorganic phosphorus concentration. Short-term donors and long-term donors manifest a somewhat different hemodilutional response to plasmapheresis.", "contents": "Plasmapheresis-induced hemodilution and its effects on serum constituents. Samples were obtained from 23 plasmapheresis donors before, during, and after double plasmapheresis. Seventeen chemical analyses were performed on these specimens and the results were subjected to statistical analysis. Representative samples can be obtained from plasmapheresis donors before the procedure has begun, immediately after the first unit of whole blood has been removed, or 15 minutes after the completion of the entire procedure. The sample obtained after the first unit of whole blood has been removed will show dilutional lowering of the uric acid concentration and the 15-minute equilibration sample will show dilutional lowering of the inorganic phosphorus concentration. Short-term donors and long-term donors manifest a somewhat different hemodilutional response to plasmapheresis."} {"id": "PMID:1258118", "title": "Optimum centrifugation conditions for the preparation of platelet and plasma products.", "content": "Units of whole blood were centrifuged for various periods of times and at various speeds to prepare platelet-rich plasma. It was found that several sets of centrifugation conditions resulted in an optimum yield of platelets and plasma. This optimum was approximately 8.3 x 10(10) platelets in 245 ml of plasma. When platelet-rich plasma was centrifuged, a maximum of approximately 95 per cent of the platelets could be recovered in the concentrate. Although this maximum was also achieved by several sets of centrifugation conditions, the most efficient method was 3,800 RPM (3731 x g) for four minutes at speed.", "contents": "Optimum centrifugation conditions for the preparation of platelet and plasma products. Units of whole blood were centrifuged for various periods of times and at various speeds to prepare platelet-rich plasma. It was found that several sets of centrifugation conditions resulted in an optimum yield of platelets and plasma. This optimum was approximately 8.3 x 10(10) platelets in 245 ml of plasma. When platelet-rich plasma was centrifuged, a maximum of approximately 95 per cent of the platelets could be recovered in the concentrate. Although this maximum was also achieved by several sets of centrifugation conditions, the most efficient method was 3,800 RPM (3731 x g) for four minutes at speed."} {"id": "PMID:1258116", "title": "The quality of over- and undercollected blood for transfusion.", "content": "Whole blood was collected in increments varying from 100 g to 600 g into plastic containers intended for 450 ml collections. In order to determine the clinical usefulness of over and undercollected bloods, red blood cell survival studies were performed after 21 and 28 days of storage and in vitro measurements were performed weekly throughout the storage period. The red blood cell survival of 21-day-old CPD bloods was acceptable if as little as 300 g of blood were collected whereas a minimum of 400 g of blood was necessary to provide normal survival after 21 days storage in ACD solution. If as much as 600 g of whole blood were collected into a standard ACD or CPD blood pack, the red blood cell survival was within normal limits after 21 days of storage. These data demonstrate the limits to which over- and undercollected units can be utilized in transfusion therapy.", "contents": "The quality of over- and undercollected blood for transfusion. Whole blood was collected in increments varying from 100 g to 600 g into plastic containers intended for 450 ml collections. In order to determine the clinical usefulness of over and undercollected bloods, red blood cell survival studies were performed after 21 and 28 days of storage and in vitro measurements were performed weekly throughout the storage period. The red blood cell survival of 21-day-old CPD bloods was acceptable if as little as 300 g of blood were collected whereas a minimum of 400 g of blood was necessary to provide normal survival after 21 days storage in ACD solution. If as much as 600 g of whole blood were collected into a standard ACD or CPD blood pack, the red blood cell survival was within normal limits after 21 days of storage. These data demonstrate the limits to which over- and undercollected units can be utilized in transfusion therapy."} {"id": "PMID:1258120", "title": "Donor and nondonor motivations.", "content": "In an attempt to gain insight into the motivations of blood donors and nondonors, two paper and pencil questionnaires were developed and mailed to approximately 7,000 individuals. In response, 1,429 nondonors and 200 donors completed and returned usable questionnaires. Among donors, awareness of the need for blood, altruism, and investment for the future (blood credit) were the chief motivating factors. Among nondonors the major deterrent was belief in medical disqualification. Of the 33 per cent who claimed medical disqualification, 40 per cent gave clearly invalid or questionable reasons. Fear, while a substantial factor among nondonors, was not as great a deterrent to blood donation as had been previously thought. A dimension focusing upon failure to confront the issue of donating was derived and found to equal or exceed fear in importance. The influence of such items as sex, age, number of donations, and number of children on reasons expressed was examined. The major results were compared with the findings of previous studies. An approach-avoidance model of blood donation was outlined, and implications for donor recruitment are discussed.", "contents": "Donor and nondonor motivations. In an attempt to gain insight into the motivations of blood donors and nondonors, two paper and pencil questionnaires were developed and mailed to approximately 7,000 individuals. In response, 1,429 nondonors and 200 donors completed and returned usable questionnaires. Among donors, awareness of the need for blood, altruism, and investment for the future (blood credit) were the chief motivating factors. Among nondonors the major deterrent was belief in medical disqualification. Of the 33 per cent who claimed medical disqualification, 40 per cent gave clearly invalid or questionable reasons. Fear, while a substantial factor among nondonors, was not as great a deterrent to blood donation as had been previously thought. A dimension focusing upon failure to confront the issue of donating was derived and found to equal or exceed fear in importance. The influence of such items as sex, age, number of donations, and number of children on reasons expressed was examined. The major results were compared with the findings of previous studies. An approach-avoidance model of blood donation was outlined, and implications for donor recruitment are discussed."} {"id": "PMID:1258127", "title": "Kidney preservation: perfusion versus cold storage-1975.", "content": "In order to compare the efficacy of simple hypothermic preservation of cadaver kidneys in Collins solution with preservation by pulsatile perfusion, data were gathered on over 1000 transplants between December 1973 and June 1975. In this series of new patient data, it was found that the 1-year thansplant survival rate of 59%+5% in 89 kidneys preserved in Collins solution was significantly better than the 41% + 3% rate found with 358 kidneys preserved by the Belzer machine (p = 0.005). This survival rate was better than the 47% + 3% rate in 421 kidneys preserved on the Waters machine (p = 0.05), and the 34% + 6% rate of 97 kidneys preserved by cold storage in Sacks solution (p = 0.005). The difference in centers probably did not influence the data, since 28 centers submitted data on the Collins-preserved kidneys. In addition, 43 of the 89 kidneys. In addition, 43 of the 89 kidneys stored in Collins solution had been shared between centers.", "contents": "Kidney preservation: perfusion versus cold storage-1975. In order to compare the efficacy of simple hypothermic preservation of cadaver kidneys in Collins solution with preservation by pulsatile perfusion, data were gathered on over 1000 transplants between December 1973 and June 1975. In this series of new patient data, it was found that the 1-year thansplant survival rate of 59%+5% in 89 kidneys preserved in Collins solution was significantly better than the 41% + 3% rate found with 358 kidneys preserved by the Belzer machine (p = 0.005). This survival rate was better than the 47% + 3% rate in 421 kidneys preserved on the Waters machine (p = 0.05), and the 34% + 6% rate of 97 kidneys preserved by cold storage in Sacks solution (p = 0.005). The difference in centers probably did not influence the data, since 28 centers submitted data on the Collins-preserved kidneys. In addition, 43 of the 89 kidneys. In addition, 43 of the 89 kidneys stored in Collins solution had been shared between centers."} {"id": "PMID:1258128", "title": "Evaluation of a fluid-controlled artificial heart.", "content": "The Zurich A. H. is a pneumatic drive biventricular cardiac prosthesis with tubular silicone rubber membrane, tilting discvalves, and fluid control system. Membrane position is monitored throughout the cardiac cycle to prevent systolic membrane collapse or insufficient diastolic filling. This A. H. was implanted in 25 dogs weighing 23-50 kg. In five animals, the A. H. performed satisfactorily for more than 24 hr. At an average flow rate of 60-90 ml/min per kg, the aortic pressure ranged from 80 to 100 mm Hg, and both left and right atrial pressures were within normal range. The animals were awake, and they breathed spontaneously after 24 hr; average plasma hemoglobin levels averaged 91 mg/100 ml, and platelet counts decreased to 65,000 cu mm. In three animals subjected to the A. H. pump for 24 hr, the A. H. was removed and replaced with a transplant. Adequate transplant function was obtained, but there were no long-term survivors. Adequate hemostasis, sepsis, and complex organ dysfunctions associated with prolonged pumping are currently the main biologic problems.", "contents": "Evaluation of a fluid-controlled artificial heart. The Zurich A. H. is a pneumatic drive biventricular cardiac prosthesis with tubular silicone rubber membrane, tilting discvalves, and fluid control system. Membrane position is monitored throughout the cardiac cycle to prevent systolic membrane collapse or insufficient diastolic filling. This A. H. was implanted in 25 dogs weighing 23-50 kg. In five animals, the A. H. performed satisfactorily for more than 24 hr. At an average flow rate of 60-90 ml/min per kg, the aortic pressure ranged from 80 to 100 mm Hg, and both left and right atrial pressures were within normal range. The animals were awake, and they breathed spontaneously after 24 hr; average plasma hemoglobin levels averaged 91 mg/100 ml, and platelet counts decreased to 65,000 cu mm. In three animals subjected to the A. H. pump for 24 hr, the A. H. was removed and replaced with a transplant. Adequate transplant function was obtained, but there were no long-term survivors. Adequate hemostasis, sepsis, and complex organ dysfunctions associated with prolonged pumping are currently the main biologic problems."} {"id": "PMID:1258119", "title": "Blood bank reagents: some problems related to preservatives and dyes.", "content": "Occasionally the additives used for the storage, preservation, and coloring of blood bank reagents are a source of anomalous a-glutination reactions. Discrepancies in ABO cell and serum grouping or agglutination of cells used for both antibody detection and identification may be related to the presence of these materials in blood bank reagents. These substances include acriflavin and other dyes; antibiotics, such as penicillin and neomycin; EDTA; caprylate; and occasionally saline. The literature is reviewed regarding this problem.", "contents": "Blood bank reagents: some problems related to preservatives and dyes. Occasionally the additives used for the storage, preservation, and coloring of blood bank reagents are a source of anomalous a-glutination reactions. Discrepancies in ABO cell and serum grouping or agglutination of cells used for both antibody detection and identification may be related to the presence of these materials in blood bank reagents. These substances include acriflavin and other dyes; antibiotics, such as penicillin and neomycin; EDTA; caprylate; and occasionally saline. The literature is reviewed regarding this problem."} {"id": "PMID:1258136", "title": "Studies on Theileriidae (Sporozoa) in Tanzania. I. Tick transmission of Haematoxenus veliferus.", "content": "Haematoxenus veliferus was experimentally transmitted in cattle on two occasions by the tick Amblyomma variegatum; transmission was transstadial, from nymph to adult. Theileria mutans and Cowdria ruminatium were transmitted at the same time. H. veliferus infected at least 15% of red cells in a splenectomized steer and 10% in a normal steer. One experiment on transstadial transmission from larva to nymph was unsuccessful.", "contents": "Studies on Theileriidae (Sporozoa) in Tanzania. I. Tick transmission of Haematoxenus veliferus. Haematoxenus veliferus was experimentally transmitted in cattle on two occasions by the tick Amblyomma variegatum; transmission was transstadial, from nymph to adult. Theileria mutans and Cowdria ruminatium were transmitted at the same time. H. veliferus infected at least 15% of red cells in a splenectomized steer and 10% in a normal steer. One experiment on transstadial transmission from larva to nymph was unsuccessful."} {"id": "PMID:1258137", "title": "Salmonellosis and shigellosis in Togo (West Africa), 1971-1973. I. Carrier rates in the rural population.", "content": "Carrier rates of Salmonella and Shigella in the rural population of Togo were investigated between October 1971 and January 1973. A total of 6051 stool specimens from 5075 persons living in 13 rural communities of all regions of Togo was examined. Each village was investigated twice, i.e. in the dry and rainy season, respectively. The overall carrier rate was 7.2% (Salmonella 6.6%, Shigella 0.6%). There was no significant difference in carrier rates of males and females. There was a higher prevalence of Salmonella infections in individuals over 65 years of age. Positive rates in the village varied form 2.0-19.8%. In the southern part of the country within the zone of equatorial climate positive results between 2.0% and 4.9% were observed without distinct differences between the dry and rainy season. In the central region positive rates determined in the rainy season (8.0-15.9%) were twice the rates in the dry season (4.2-7.6%). In the northern part of the country differences observed in the two investigations of each community seemed not to be related to season (2.0-19.0%). The 414 Salmonella strains belong to 133 serotypes, among them 17 new antigen combinations. Typhoid bacteria were detected in 6 subjects only; paratyphoid bacteria have not been isolated. Among Shigella strains Sh. flexneri was most frequently identified (31 of 36 strains).", "contents": "Salmonellosis and shigellosis in Togo (West Africa), 1971-1973. I. Carrier rates in the rural population. Carrier rates of Salmonella and Shigella in the rural population of Togo were investigated between October 1971 and January 1973. A total of 6051 stool specimens from 5075 persons living in 13 rural communities of all regions of Togo was examined. Each village was investigated twice, i.e. in the dry and rainy season, respectively. The overall carrier rate was 7.2% (Salmonella 6.6%, Shigella 0.6%). There was no significant difference in carrier rates of males and females. There was a higher prevalence of Salmonella infections in individuals over 65 years of age. Positive rates in the village varied form 2.0-19.8%. In the southern part of the country within the zone of equatorial climate positive results between 2.0% and 4.9% were observed without distinct differences between the dry and rainy season. In the central region positive rates determined in the rainy season (8.0-15.9%) were twice the rates in the dry season (4.2-7.6%). In the northern part of the country differences observed in the two investigations of each community seemed not to be related to season (2.0-19.0%). The 414 Salmonella strains belong to 133 serotypes, among them 17 new antigen combinations. Typhoid bacteria were detected in 6 subjects only; paratyphoid bacteria have not been isolated. Among Shigella strains Sh. flexneri was most frequently identified (31 of 36 strains)."} {"id": "PMID:1258138", "title": "Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. II. Pathology.", "content": "The injection of living microfilariae of Onchocerca volvulus into the vitreous or immediately beneath the retina of rabbits gave rise to a variable degree of choroiditis. Uveal inflammation was most marked in eyes inoculated directly into the retina and subretinal tissue. The choroiditis was characterised by lymphocytic, plasma cell and eosinophil infiltration and was associated in many instances with degeneration of the overlying retina and pigment epithelium. In the eyes of animals killed more than 40 days after inoculation with microfilariae the leucocytic infiltration was usually mild or even absent, and the predominant finding was circumscribed atrophy and degeneration of the retina. It is concluded that the pathogenesis of the lesions in posterior segment onchocerciasis is basically inflammatory with, possibly, a direct toxic action of the microfilariae on the retina.", "contents": "Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. II. Pathology. The injection of living microfilariae of Onchocerca volvulus into the vitreous or immediately beneath the retina of rabbits gave rise to a variable degree of choroiditis. Uveal inflammation was most marked in eyes inoculated directly into the retina and subretinal tissue. The choroiditis was characterised by lymphocytic, plasma cell and eosinophil infiltration and was associated in many instances with degeneration of the overlying retina and pigment epithelium. In the eyes of animals killed more than 40 days after inoculation with microfilariae the leucocytic infiltration was usually mild or even absent, and the predominant finding was circumscribed atrophy and degeneration of the retina. It is concluded that the pathogenesis of the lesions in posterior segment onchocerciasis is basically inflammatory with, possibly, a direct toxic action of the microfilariae on the retina."} {"id": "PMID:1258139", "title": "Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. I. The clinical picture.", "content": "Live microfilariae of the Cameroon forest and Sudan-savanna strains of Onchocerca volvulus were inoculated into the vitreous or into the subretinal layers of the eyes of rabbits. The lesions produced are described, and are compared with those seen in control animals, which had received inocula of microfilariae-free saline supernate introduced with a similar degree of operative trauma. Control rabbits showed only minor pigment disturbance in the retina and choroid, near the healed operation scars. Infected animals showed evidence of an inflammatory process in the eye, lasting for up to 4 weeks. Fundus lesions developed following inoculation of microfilariae into the vitreous, but they were more frequent and more severe following subretinal inoculation. The lesions produced were: pallor, vascular narrowing, and flattening of the optic disc; subretinal inflammatory exudate, giving rise to a disturbance of pigment in the retinal pigment epithelium; scattered, small choroidoretinal scars, and larger circumscribed areas of choroidoretinitis, sometimes accompanied by optic atrophy. In many eyes inoculated with microfilariae the wincing reflex was lost, indicating some visual impairment. Many of the lesions were similar to those seen in human patients with onchocerciasis, but they developed much more rapidly. Microfilariae inoculated intravenously, or into the periocular tissues, were not observed to penetrate into the eye-ball.", "contents": "Fundus lesions in the rabbit eye following inoculation of onchocerca volvulus microfilariae into the posterior segment. I. The clinical picture. Live microfilariae of the Cameroon forest and Sudan-savanna strains of Onchocerca volvulus were inoculated into the vitreous or into the subretinal layers of the eyes of rabbits. The lesions produced are described, and are compared with those seen in control animals, which had received inocula of microfilariae-free saline supernate introduced with a similar degree of operative trauma. Control rabbits showed only minor pigment disturbance in the retina and choroid, near the healed operation scars. Infected animals showed evidence of an inflammatory process in the eye, lasting for up to 4 weeks. Fundus lesions developed following inoculation of microfilariae into the vitreous, but they were more frequent and more severe following subretinal inoculation. The lesions produced were: pallor, vascular narrowing, and flattening of the optic disc; subretinal inflammatory exudate, giving rise to a disturbance of pigment in the retinal pigment epithelium; scattered, small choroidoretinal scars, and larger circumscribed areas of choroidoretinitis, sometimes accompanied by optic atrophy. In many eyes inoculated with microfilariae the wincing reflex was lost, indicating some visual impairment. Many of the lesions were similar to those seen in human patients with onchocerciasis, but they developed much more rapidly. Microfilariae inoculated intravenously, or into the periocular tissues, were not observed to penetrate into the eye-ball."} {"id": "PMID:1258140", "title": "Myiasis due to Cordylobia anthropophaga in Zambia.", "content": "Dermal or subdermal myiasis due to larvae of the African tumbu fly Cordylobia anthropophaga is described from Zambia for the first time. Differential diagnosis from the closely allied C. rodhaini is considered. A patient presenting with the lesion on the penis is described. Multiple infection with different developmental stages is discussed in relation to multiple exposure or immunity. Many cases of myiasis may not reach the attention of medical personnel because of the tendency of the mature larvae to migrate out of the lesion which subsequently heals; traditional healers, to whom the condition has been known for long, also successfully extract the larvae.", "contents": "Myiasis due to Cordylobia anthropophaga in Zambia. Dermal or subdermal myiasis due to larvae of the African tumbu fly Cordylobia anthropophaga is described from Zambia for the first time. Differential diagnosis from the closely allied C. rodhaini is considered. A patient presenting with the lesion on the penis is described. Multiple infection with different developmental stages is discussed in relation to multiple exposure or immunity. Many cases of myiasis may not reach the attention of medical personnel because of the tendency of the mature larvae to migrate out of the lesion which subsequently heals; traditional healers, to whom the condition has been known for long, also successfully extract the larvae."} {"id": "PMID:1258141", "title": "[Antibodies and immunoglobulin levels in sera from patients with African paragonimiasis (author's transl)].", "content": "96% of the P. uterobilateralis patients and 86.5% of the P. africanus patients showed a positive reaction with the homologous antigen in the passive haemagglutination test (PA). Common antigens of the two species were demonstrated by cross reactions. About 75% of the Paragonimus sera reacted also with the heterologous antigen with titres greater than or equal to 1:160. The PA test can be useful in the evaluation of the efficacy of treatment and is well suited for seroepidemiologic purposes. The complement fixation (CF) test was not suitable for serodiagnostic or seroepidemiologic studies nor for the assessment of the cure of African Paragonimiasis since antibodies persisted for at least one year after treatment. Comparative studies on levels of IgA, IgE, IgG and IgM seems to be of no diagnostic value in African paragonimiasis because no significant correlation between immunoglobulin concentration and paragonimiasis could be recognized. Very high IgE levels--up to 100 times higher than in Europeans--were found in nearly all sera. Shipment of filter papers blood specimens collected from P. africanus patient resulted in a significant decrease of antibody reactivity in all sera, the loss being about 30% in the parasitologically proven patients.", "contents": "[Antibodies and immunoglobulin levels in sera from patients with African paragonimiasis (author's transl)]. 96% of the P. uterobilateralis patients and 86.5% of the P. africanus patients showed a positive reaction with the homologous antigen in the passive haemagglutination test (PA). Common antigens of the two species were demonstrated by cross reactions. About 75% of the Paragonimus sera reacted also with the heterologous antigen with titres greater than or equal to 1:160. The PA test can be useful in the evaluation of the efficacy of treatment and is well suited for seroepidemiologic purposes. The complement fixation (CF) test was not suitable for serodiagnostic or seroepidemiologic studies nor for the assessment of the cure of African Paragonimiasis since antibodies persisted for at least one year after treatment. Comparative studies on levels of IgA, IgE, IgG and IgM seems to be of no diagnostic value in African paragonimiasis because no significant correlation between immunoglobulin concentration and paragonimiasis could be recognized. Very high IgE levels--up to 100 times higher than in Europeans--were found in nearly all sera. Shipment of filter papers blood specimens collected from P. africanus patient resulted in a significant decrease of antibody reactivity in all sera, the loss being about 30% in the parasitologically proven patients."} {"id": "PMID:1258142", "title": "Circadian periodicity of Wuchereria bancrofti in Liberia and its effect on the results of a prevalence study.", "content": "The Harmonic Wave curve of Sasa and Tanaka (1972), describing microfilarial periodicity, has been fitted to observations on 38 persons infected with W. bancrofti in Liberia, as well as to data previously obtained from the same country by other authors. The periodicity of the Liberian strain was similar to that of periodic forms of W. bancrofti in Southeast Asia and Japan. The effect of periodicity on microfilaraemia prevalence survey results has been examined, using data from a recent study in coastal Liberia. Although prevalence rates appear to be little affected the median microfilarial densities (MfD50) vary condiserably according as to whether a population is examined in the early evening or late at night.", "contents": "Circadian periodicity of Wuchereria bancrofti in Liberia and its effect on the results of a prevalence study. The Harmonic Wave curve of Sasa and Tanaka (1972), describing microfilarial periodicity, has been fitted to observations on 38 persons infected with W. bancrofti in Liberia, as well as to data previously obtained from the same country by other authors. The periodicity of the Liberian strain was similar to that of periodic forms of W. bancrofti in Southeast Asia and Japan. The effect of periodicity on microfilaraemia prevalence survey results has been examined, using data from a recent study in coastal Liberia. Although prevalence rates appear to be little affected the median microfilarial densities (MfD50) vary condiserably according as to whether a population is examined in the early evening or late at night."} {"id": "PMID:1258143", "title": "[Mineral contents of the blood and chemical composition of the muscles of trichinella-infected piglets (author's transl)].", "content": "Three piglets of 22 kg were infected each with 10 larvae of Trichinella spiralis per g body weight. In the blood plasma the contents of several electrolytes were measured twice per week to day 45 post infection (p.i.). These electrolytes, water, dry matter, lipids, nitrogen and ash contents were assayed on samples of muscles of each animal after they were sacrificed on day 61 p.i. Three noninfected piglets served as controls. In blood plasma the contents of Na, Mg, Ca, Cu, Zn and chloride decreased, K- and Fe-contents increased. This process started at earliest on day 7 p.i. Only the Na- and the Fe-contents returned partially to preinfection values up to the end of the investigation period. In the muscles the Ca-contents were increased strongly on day 61 p.i., the Cu- and Zn-contents not the the same extent. There was a decrease in Fe, P, K, Na and Mg contents. The water contents of the muscles increased from 0.53 to 4.9%. The portion of dry matter was reduced correspondingly. Lipids contents increased 2.0 and 127.9% and ash contents 1.7 to 4.4%. Nitrogen contents were reduced by 2.5 to 5.9%.", "contents": "[Mineral contents of the blood and chemical composition of the muscles of trichinella-infected piglets (author's transl)]. Three piglets of 22 kg were infected each with 10 larvae of Trichinella spiralis per g body weight. In the blood plasma the contents of several electrolytes were measured twice per week to day 45 post infection (p.i.). These electrolytes, water, dry matter, lipids, nitrogen and ash contents were assayed on samples of muscles of each animal after they were sacrificed on day 61 p.i. Three noninfected piglets served as controls. In blood plasma the contents of Na, Mg, Ca, Cu, Zn and chloride decreased, K- and Fe-contents increased. This process started at earliest on day 7 p.i. Only the Na- and the Fe-contents returned partially to preinfection values up to the end of the investigation period. In the muscles the Ca-contents were increased strongly on day 61 p.i., the Cu- and Zn-contents not the the same extent. There was a decrease in Fe, P, K, Na and Mg contents. The water contents of the muscles increased from 0.53 to 4.9%. The portion of dry matter was reduced correspondingly. Lipids contents increased 2.0 and 127.9% and ash contents 1.7 to 4.4%. Nitrogen contents were reduced by 2.5 to 5.9%."} {"id": "PMID:1258144", "title": "Sylvatic echinococcosis in Argentina. II. Susceptibility of wild carnivores to Echinococcus granulosus (Batsch, 1786) and host-induced morphological variation.", "content": "Domestic dogs and cats, 3 fox species, Dusicyon culpaeus (Molina,1782), D, griseus (Gray, 1837) and D. gymnocercus (Thomas, 1914), Geoffroy's cats, Felis geoffroyi (D'Orbigny and Gervais, 1843), and grisons, Galictus cuja (Molina, 1782) were fed larvae of Echinococcus granulosus (Batsch, 1786) from domestic sheep in Argentina. Dogs and the 3 species of foxes became infected. The susceptibility of D. culpaeus compared favorably to that of dogs. Most D. griseus and D. gymnocercus were less susceptible than dogs but gravid strobilae were recovered from some animals of both species. Eggs from strobilae in dogs and Dusicyon spp. were infective to CF1 mice. The mean strobilar length and the diameters of the rostellar pad and suckers of worms in foxes were significantly reduced when compared with previously reported data for strobilae from dogs. The potential significance of Dusicyon spp. as reservoir hosts of E. granulosus in Argentina is discussed as is the confusion surrounding the taxonomic identification of cestode infections previously reported from these wild carnivores. It is suggested that Echinococcus spp. reported from Argentine foxes are E. granulosus and that foxes become infected by killing and scavenging on sheep in localities where E. granulosus is endemic.", "contents": "Sylvatic echinococcosis in Argentina. II. Susceptibility of wild carnivores to Echinococcus granulosus (Batsch, 1786) and host-induced morphological variation. Domestic dogs and cats, 3 fox species, Dusicyon culpaeus (Molina,1782), D, griseus (Gray, 1837) and D. gymnocercus (Thomas, 1914), Geoffroy's cats, Felis geoffroyi (D'Orbigny and Gervais, 1843), and grisons, Galictus cuja (Molina, 1782) were fed larvae of Echinococcus granulosus (Batsch, 1786) from domestic sheep in Argentina. Dogs and the 3 species of foxes became infected. The susceptibility of D. culpaeus compared favorably to that of dogs. Most D. griseus and D. gymnocercus were less susceptible than dogs but gravid strobilae were recovered from some animals of both species. Eggs from strobilae in dogs and Dusicyon spp. were infective to CF1 mice. The mean strobilar length and the diameters of the rostellar pad and suckers of worms in foxes were significantly reduced when compared with previously reported data for strobilae from dogs. The potential significance of Dusicyon spp. as reservoir hosts of E. granulosus in Argentina is discussed as is the confusion surrounding the taxonomic identification of cestode infections previously reported from these wild carnivores. It is suggested that Echinococcus spp. reported from Argentine foxes are E. granulosus and that foxes become infected by killing and scavenging on sheep in localities where E. granulosus is endemic."} {"id": "PMID:1258145", "title": "[Influence of xanthine oxidase on duration of asexual cycle of Plasmodium vinckei in the mouse (author's transl)].", "content": "Injection of 1.2 U xanthine oxidase in Plasmodium vinckei-infected mice showing high parasitemias prolonged the duration of the asexual cycle by about 10% and slightly decreased the multiplication factor of the parasites. This appears to be of theoretical interest only since the rapid and fatal course of the infection remained essentially unaltered.", "contents": "[Influence of xanthine oxidase on duration of asexual cycle of Plasmodium vinckei in the mouse (author's transl)]. Injection of 1.2 U xanthine oxidase in Plasmodium vinckei-infected mice showing high parasitemias prolonged the duration of the asexual cycle by about 10% and slightly decreased the multiplication factor of the parasites. This appears to be of theoretical interest only since the rapid and fatal course of the infection remained essentially unaltered."} {"id": "PMID:1258146", "title": "Antigen-induced lymphocyte blastogenesis in a hookworm (Necator americanus) infection in man.", "content": "A lymphocyte blastogenic technique was employed to examine cell-mediated immunity in a Necator americanus infection. Infective third-stage larvae of N. americanus were jsed for antigen preparation, and lymphocyte cultures were prepared from peripheral blood taken on days 3, 17, and 51 after infection with 250 third-stage larvae of N. americanus. At 3 days post-infection lymphocyte transformation was not induced; at 17 and 51 days after infection significant transformation was obtained.", "contents": "Antigen-induced lymphocyte blastogenesis in a hookworm (Necator americanus) infection in man. A lymphocyte blastogenic technique was employed to examine cell-mediated immunity in a Necator americanus infection. Infective third-stage larvae of N. americanus were jsed for antigen preparation, and lymphocyte cultures were prepared from peripheral blood taken on days 3, 17, and 51 after infection with 250 third-stage larvae of N. americanus. At 3 days post-infection lymphocyte transformation was not induced; at 17 and 51 days after infection significant transformation was obtained."} {"id": "PMID:1258147", "title": "Observations on a herd of beef cattle maintained in a tsetse area. II. Assessment of the development of immunity in association with trypanocidal drug treatment.", "content": "Three groups of Boran cattle were maintained under different trypanocidal drug regimes for 29 months in an area of \"medium\" tsetse challenge. The development of immunity to trypanosmiasis in the cattle was assessed on the basis of changes in trypanocidal drug requirement, development of parasitaemia, ability to maintain normal blood values, growth and response to challenge after the withdrawal of the drugs. Observations were also made on serum antibody content by immunofluorescence and on serum immunoglobulin levels. Cattle treated with Berenil on the development of clinical disease developed a partial immunity to trypanosomiasis after two years. Cattle treated as a group with Berenil on the development of patent parasitaemia in any one animal of the group did not develop immunity. Cattle treated as a group with Samorin using the same criterion for treatment developed a degree of immunity to the disease. It was concluded that group treatment with Samorin was the most suitable of the three regimes examined for the maintenance of beef cattle is a tsetse infested area.", "contents": "Observations on a herd of beef cattle maintained in a tsetse area. II. Assessment of the development of immunity in association with trypanocidal drug treatment. Three groups of Boran cattle were maintained under different trypanocidal drug regimes for 29 months in an area of \"medium\" tsetse challenge. The development of immunity to trypanosmiasis in the cattle was assessed on the basis of changes in trypanocidal drug requirement, development of parasitaemia, ability to maintain normal blood values, growth and response to challenge after the withdrawal of the drugs. Observations were also made on serum antibody content by immunofluorescence and on serum immunoglobulin levels. Cattle treated with Berenil on the development of clinical disease developed a partial immunity to trypanosomiasis after two years. Cattle treated as a group with Berenil on the development of patent parasitaemia in any one animal of the group did not develop immunity. Cattle treated as a group with Samorin using the same criterion for treatment developed a degree of immunity to the disease. It was concluded that group treatment with Samorin was the most suitable of the three regimes examined for the maintenance of beef cattle is a tsetse infested area."} {"id": "PMID:1258150", "title": "Serum proteins, blood and plasma volumes in experimental Trypanosoma vivax infections of sheep and goats.", "content": "Measurements of blood and plasma volumes using 131I-albumin, and of red cell volume using 51Cr in goats and sheep infected with Trypanosoma vivax for 1 to 2 months (at which time the anaemia was severe) showed statistically significant increases in blood volume (29 per cent and 57 per cent) and plasma volume (44 per cent and 59 per cent), and decreases in red cell volume per kilogram body weight (49 per cent and 50 per cent) in goats and sheep respectively. Total serum proteins and gamma globulins increased, while serum albumin decreased, in T. vivax infected sheep and goats. These findings indicate that the anaemia manifested, with mean packed cell volume decreased by 60 per cent and 47 per cent in goats and sheep respectively at the time of red cell volume measurements, is attributable partly to haemodilution and partly to an actual decrease in total volume oc circulating red blood cells.", "contents": "Serum proteins, blood and plasma volumes in experimental Trypanosoma vivax infections of sheep and goats. Measurements of blood and plasma volumes using 131I-albumin, and of red cell volume using 51Cr in goats and sheep infected with Trypanosoma vivax for 1 to 2 months (at which time the anaemia was severe) showed statistically significant increases in blood volume (29 per cent and 57 per cent) and plasma volume (44 per cent and 59 per cent), and decreases in red cell volume per kilogram body weight (49 per cent and 50 per cent) in goats and sheep respectively. Total serum proteins and gamma globulins increased, while serum albumin decreased, in T. vivax infected sheep and goats. These findings indicate that the anaemia manifested, with mean packed cell volume decreased by 60 per cent and 47 per cent in goats and sheep respectively at the time of red cell volume measurements, is attributable partly to haemodilution and partly to an actual decrease in total volume oc circulating red blood cells."} {"id": "PMID:1258151", "title": "The prevalence and diagnosis of Trypanosoma evansi infection in camels in southern Ethiopia.", "content": "An investigation of trypanosomiasis in camels indicated a high prevalence of infection in southern Ethiopia. Various direct and indirect laboratory methods for the diagnosis of infection with Trypanosoma evansi were compared and evaluated. At the present time inoculation of camel blood into laboratory rodents appears to be the best direct diagnostic method. The formol-gel test and the Takata test appear to be the most sensitive and accurate of the biochemical methods available. However, there still remains a need for an accurate diagnostic test for individual cases.", "contents": "The prevalence and diagnosis of Trypanosoma evansi infection in camels in southern Ethiopia. An investigation of trypanosomiasis in camels indicated a high prevalence of infection in southern Ethiopia. Various direct and indirect laboratory methods for the diagnosis of infection with Trypanosoma evansi were compared and evaluated. At the present time inoculation of camel blood into laboratory rodents appears to be the best direct diagnostic method. The formol-gel test and the Takata test appear to be the most sensitive and accurate of the biochemical methods available. However, there still remains a need for an accurate diagnostic test for individual cases."} {"id": "PMID:1258154", "title": "[Comparative studies of the properties of aldolase isoenzymes A-C in normal rabbit brain and in skeletal muscles from rabbits with E-avitaminosis dystrophy].", "content": "By means of fructose-1,6-diphosphate selective elution of aldolase isoenzymic forms from the phosphocellulose column the izoenzyme AC3 was isolated preparatively from the muscles rabbits with experimental E-avitaminosis muscular dystrophy. The specific activity of aldolase A4 and AC3 with pathology differs from that at normal state by fructose-1,6-diphosphate and fructose-1-monophosphate. As to the electrophoretic activity the isoenzymes A4 and AC3 are similar to the same isoforms at normal state. The values of the Michaelis constants and maximal rate are determined for aldolases A4, AC3 and C4 at normal state and for A4 and AC3 with E-avitaminosis. Differences in these parameters are found relative to two substrates for A4 aldolase and AC3-hybrid at normal state and with dystrophy.", "contents": "[Comparative studies of the properties of aldolase isoenzymes A-C in normal rabbit brain and in skeletal muscles from rabbits with E-avitaminosis dystrophy]. By means of fructose-1,6-diphosphate selective elution of aldolase isoenzymic forms from the phosphocellulose column the izoenzyme AC3 was isolated preparatively from the muscles rabbits with experimental E-avitaminosis muscular dystrophy. The specific activity of aldolase A4 and AC3 with pathology differs from that at normal state by fructose-1,6-diphosphate and fructose-1-monophosphate. As to the electrophoretic activity the isoenzymes A4 and AC3 are similar to the same isoforms at normal state. The values of the Michaelis constants and maximal rate are determined for aldolases A4, AC3 and C4 at normal state and for A4 and AC3 with E-avitaminosis. Differences in these parameters are found relative to two substrates for A4 aldolase and AC3-hybrid at normal state and with dystrophy."} {"id": "PMID:1258155", "title": "[The effect of weight loss caused by tissue dehydration on changes in carbohydrate metabolism under physical load].", "content": "Moderate dehydration of rats led to a certain reduction of glycogen content in the liver and muscles. The analogous changes were observed when the animals were subjected to physical load. The previous dehydration also causes a delay in glycogen l-vel restoration in tissue after work is over. Under usual conditions physical load which wrestlers underwent on a veloergograph caused a certain increase in the concentration of lactic and pyruvic acids in blood. Against a background of previous dehydration physical load of the same intensity caused a more considerable change in these values. Consequently, even moderate dehydration of an organism practised by some sportsmen leads to considerable change in certain values of carbohydrate metabolism. It may be one of the reasons of a negative influence produced by weight loss on working capacity.", "contents": "[The effect of weight loss caused by tissue dehydration on changes in carbohydrate metabolism under physical load]. Moderate dehydration of rats led to a certain reduction of glycogen content in the liver and muscles. The analogous changes were observed when the animals were subjected to physical load. The previous dehydration also causes a delay in glycogen l-vel restoration in tissue after work is over. Under usual conditions physical load which wrestlers underwent on a veloergograph caused a certain increase in the concentration of lactic and pyruvic acids in blood. Against a background of previous dehydration physical load of the same intensity caused a more considerable change in these values. Consequently, even moderate dehydration of an organism practised by some sportsmen leads to considerable change in certain values of carbohydrate metabolism. It may be one of the reasons of a negative influence produced by weight loss on working capacity."} {"id": "PMID:1258156", "title": "[Anticlotting activity of fragment D from fibrinogen and fibrin and its dependence on calcium presence when fragments are obtained from fibrinogen].", "content": "The CaCl2 concentration of about 10(-4) M slightly reduces the proteolytic fibrinogen degradation and greatly increases the anticlotting activity in the arising fragments D. With a rise in the CaCl2 concentration to 10(-2) M a subsequent limitation of proteolysis occurs, but less active fragments D are formed. These facts suggest that a moderate restriction of peptide bond cleavage enhances the fragment D activity, whereas excessive restriction exhibits an adverse effect. Fragment D originating from noncross-linked fibrin inhibits clotting stronger than its counterpart--the fibrinogen derivative. The following explanation seems plausible. Certain sites of the intact molecules, essential for the inhibitory activity of the prospective fragment D, become somewhat \"enzyme-proof\" (due to intermolecular links characteristic of polymeric fibrin), thus, avoiding proteolytic damage. Calcium ions presented at the optimum concentration may act similarly.", "contents": "[Anticlotting activity of fragment D from fibrinogen and fibrin and its dependence on calcium presence when fragments are obtained from fibrinogen]. The CaCl2 concentration of about 10(-4) M slightly reduces the proteolytic fibrinogen degradation and greatly increases the anticlotting activity in the arising fragments D. With a rise in the CaCl2 concentration to 10(-2) M a subsequent limitation of proteolysis occurs, but less active fragments D are formed. These facts suggest that a moderate restriction of peptide bond cleavage enhances the fragment D activity, whereas excessive restriction exhibits an adverse effect. Fragment D originating from noncross-linked fibrin inhibits clotting stronger than its counterpart--the fibrinogen derivative. The following explanation seems plausible. Certain sites of the intact molecules, essential for the inhibitory activity of the prospective fragment D, become somewhat \"enzyme-proof\" (due to intermolecular links characteristic of polymeric fibrin), thus, avoiding proteolytic damage. Calcium ions presented at the optimum concentration may act similarly."} {"id": "PMID:1258157", "title": "[Effect of heparin on oxidative phosphorylation and ultrastructure of rabbit heart mitochondria].", "content": "The effect of heparin on isolated rabbit heart mitochondria was studied in usual clinical (0.25 u/ml) and higher doses. Hepain concentration 0.25 u/ml stimulated respiration in the state 4, decreased ADP/O ratio and phosphorylation rate and did not affect mitochondria ultrastructure. Higher concentration caused two-phase changes in respiration-short-time stimulation with the following inhibition, oxidative phosphorylation (respiratory control, ADP/O, phosphorylation rate) was progressively depressed and decoupled. The mitochondria ultrastructure is changed under the influence of 1.25 u/ml and of higher doses; the external membrane lost its two-layer character, the crista were converted into a small granular mass. Concentration of 1.25 u/ml transformed many mitochondria into empty vesicles.", "contents": "[Effect of heparin on oxidative phosphorylation and ultrastructure of rabbit heart mitochondria]. The effect of heparin on isolated rabbit heart mitochondria was studied in usual clinical (0.25 u/ml) and higher doses. Hepain concentration 0.25 u/ml stimulated respiration in the state 4, decreased ADP/O ratio and phosphorylation rate and did not affect mitochondria ultrastructure. Higher concentration caused two-phase changes in respiration-short-time stimulation with the following inhibition, oxidative phosphorylation (respiratory control, ADP/O, phosphorylation rate) was progressively depressed and decoupled. The mitochondria ultrastructure is changed under the influence of 1.25 u/ml and of higher doses; the external membrane lost its two-layer character, the crista were converted into a small granular mass. Concentration of 1.25 u/ml transformed many mitochondria into empty vesicles."} {"id": "PMID:1258158", "title": "[Electrophoretic characterization of hemoglobin in rats at different ages].", "content": "Under conditions of electrophoresis in polyacrylamide gel hemoglobin dissolved in 0.1% solution of NaCl is divided into two components. In old rats the amount of a \"slow\" component increases. When stored in vitro the whole \"quick\" component is converted into a \"slow\" one, however in the former case the process is accompanied by a simultaneous decrease in the ratio between SH- and S--S-groups, in the latter case such phenomenon is absent.", "contents": "[Electrophoretic characterization of hemoglobin in rats at different ages]. Under conditions of electrophoresis in polyacrylamide gel hemoglobin dissolved in 0.1% solution of NaCl is divided into two components. In old rats the amount of a \"slow\" component increases. When stored in vitro the whole \"quick\" component is converted into a \"slow\" one, however in the former case the process is accompanied by a simultaneous decrease in the ratio between SH- and S--S-groups, in the latter case such phenomenon is absent."} {"id": "PMID:1258159", "title": "[Role of intramolecular bonds in stability of certain enzymes of the cellulolytic complex].", "content": "Stability of C1- and C2-cellulases, CX-exo- and CX-endoglucanases and beta-glucosidase of Aspergillus awamori was studied as affected by monoatomic aliphatic alcohols --methanol, ethanol, propanol and isopropanol; bi- and triatomic alcohols - ethylene glycol and glycerol, urea as well as detergents of dodecyl sulphate and sodium nonilate. The mentioned enzymes are established to manifest the highest activity in 40-60% glycerol. It is also shown that their stability is changed differently under the effect of other alcohols, urea and detergents. The latter testifies to the fact that the studied enzymes are nonidentical, in particular, they differ between themselves by a ratio of intramolecular forces which stabilize their macrostructure.", "contents": "[Role of intramolecular bonds in stability of certain enzymes of the cellulolytic complex]. Stability of C1- and C2-cellulases, CX-exo- and CX-endoglucanases and beta-glucosidase of Aspergillus awamori was studied as affected by monoatomic aliphatic alcohols --methanol, ethanol, propanol and isopropanol; bi- and triatomic alcohols - ethylene glycol and glycerol, urea as well as detergents of dodecyl sulphate and sodium nonilate. The mentioned enzymes are established to manifest the highest activity in 40-60% glycerol. It is also shown that their stability is changed differently under the effect of other alcohols, urea and detergents. The latter testifies to the fact that the studied enzymes are nonidentical, in particular, they differ between themselves by a ratio of intramolecular forces which stabilize their macrostructure."} {"id": "PMID:1258162", "title": "[Aminoacylation of rat liver tRNA under different experimental conditions].", "content": "The studies were performed in methionine, lysine and glycine aminoacylation of the total tRNA preparations isolated from the rat liver 3 h after total irradiation with X-rays with a dose of 800 R as well as after administration of nicotinic acid and proserine 4 h before decapitation of the animals. The tRNA preparations isolated from the irradiated animals liver are established to accept methionine, glycine and lysine to a less extent as compared with the normal state. The tRNA preparations isolated from the animal liver after administration of nicotinic acid accept methionine and glycine to a less degree and in the tRNA preparations from the liver of animals which were administered proserine the acceptance intensity lowers only with respect to lysine.", "contents": "[Aminoacylation of rat liver tRNA under different experimental conditions]. The studies were performed in methionine, lysine and glycine aminoacylation of the total tRNA preparations isolated from the rat liver 3 h after total irradiation with X-rays with a dose of 800 R as well as after administration of nicotinic acid and proserine 4 h before decapitation of the animals. The tRNA preparations isolated from the irradiated animals liver are established to accept methionine, glycine and lysine to a less extent as compared with the normal state. The tRNA preparations isolated from the animal liver after administration of nicotinic acid accept methionine and glycine to a less degree and in the tRNA preparations from the liver of animals which were administered proserine the acceptance intensity lowers only with respect to lysine."} {"id": "PMID:1258161", "title": "[Changes in the content of sulphydryl groups in rat tissues under the effect of muscular activity].", "content": "The muscular activity was established to affect the content of SH-groups in the tissues of skeletal muscles and myocardium. During 15-minute swimming the total content of sulphydryl groups lowers in them due to a decrease in the content of protein and nonprotein fractions. Swimming for 2-2.5 h has no effect on the content of SH-groups in the skeletal muscles and evokes its decrease in the myocardium. A more prolonged swimming (4.5-5 h) causes an increase in the amount of sulphydryl groups in the skeletal muscles due to its growth in the protein fraction. In the myocardium the total content of SH-groups and nonprotein fractions lowers. A long muscular load has no effect on the content of sulphydryl groups in the liver.", "contents": "[Changes in the content of sulphydryl groups in rat tissues under the effect of muscular activity]. The muscular activity was established to affect the content of SH-groups in the tissues of skeletal muscles and myocardium. During 15-minute swimming the total content of sulphydryl groups lowers in them due to a decrease in the content of protein and nonprotein fractions. Swimming for 2-2.5 h has no effect on the content of SH-groups in the skeletal muscles and evokes its decrease in the myocardium. A more prolonged swimming (4.5-5 h) causes an increase in the amount of sulphydryl groups in the skeletal muscles due to its growth in the protein fraction. In the myocardium the total content of SH-groups and nonprotein fractions lowers. A long muscular load has no effect on the content of sulphydryl groups in the liver."} {"id": "PMID:1258160", "title": "[Content of nucleic acids in the mammary gland tissues and blood plasma in goats during lactation].", "content": "The experimental data concerning changes in the content of nucleic acids in the mammary gland tissue as well as in the arterial and venous blood plasm are presented according to the months of lactation. The highest content of RNA phosphorus in the mammary gland tissue is observed the first week after lambing and then in the period of intensive lactation it is maintained at a relatively high level and only in the seventh month it decreases. The content of DNA phosphorus in the mammary gland tissue during lactation gradually lowers. In the plasm of arterial and venous blood the content of RNA phosphorus during lactation changes in the same regularity as in the mammary gland tissue. The content of DNA phosphorus remains unchanged.", "contents": "[Content of nucleic acids in the mammary gland tissues and blood plasma in goats during lactation]. The experimental data concerning changes in the content of nucleic acids in the mammary gland tissue as well as in the arterial and venous blood plasm are presented according to the months of lactation. The highest content of RNA phosphorus in the mammary gland tissue is observed the first week after lambing and then in the period of intensive lactation it is maintained at a relatively high level and only in the seventh month it decreases. The content of DNA phosphorus in the mammary gland tissue during lactation gradually lowers. In the plasm of arterial and venous blood the content of RNA phosphorus during lactation changes in the same regularity as in the mammary gland tissue. The content of DNA phosphorus remains unchanged."} {"id": "PMID:1258163", "title": "[Studies on the possibility of mRNA translation for interferon in the heterologic systems].", "content": "It is established that mRNA for interoferon which is isolated from free polysomas bound with endoplasmic reticulum can translate protein in homological and heterological systems. The predominant synthesis of interoferon is observed on the bound polysomas.", "contents": "[Studies on the possibility of mRNA translation for interferon in the heterologic systems]. It is established that mRNA for interoferon which is isolated from free polysomas bound with endoplasmic reticulum can translate protein in homological and heterological systems. The predominant synthesis of interoferon is observed on the bound polysomas."} {"id": "PMID:1258164", "title": "[Structural peculiarities of protein typical of G-myelomas].", "content": "G-myeloma protein is shown to differ by its conformation from the donor immunoglobulin G. It is characterized by a more polar surrounding of the molecule tyrosine and tryptophane residua. Under the effect of urea the changes are less considerable.", "contents": "[Structural peculiarities of protein typical of G-myelomas]. G-myeloma protein is shown to differ by its conformation from the donor immunoglobulin G. It is characterized by a more polar surrounding of the molecule tyrosine and tryptophane residua. Under the effect of urea the changes are less considerable."} {"id": "PMID:1258165", "title": "[Effects of UV-radiation of different spectral composition on content of sterols in rat skin].", "content": "When irradiating rats with sources of UV-radiation of different spectral composition a decrease in a relative content of cholesterol is found in the animal skin. Simultaneously an increase in the content of such cholestorol biosynthesis precursors as lathosterol and 7-dehydrocholesterol is observed. The formation of cholesterol photooxidation products under the effect of UV-radiation in vivo is shown. The quantitative ratios of sterols under study depend on spectral characteristics of the applied UV-radiation sources. The cholesterol photooxidation products and antirachitic compounds formed in skin under the effect of UV-radiation are supposed to take part in inhibition of cholesterol biosynthesis.", "contents": "[Effects of UV-radiation of different spectral composition on content of sterols in rat skin]. When irradiating rats with sources of UV-radiation of different spectral composition a decrease in a relative content of cholesterol is found in the animal skin. Simultaneously an increase in the content of such cholestorol biosynthesis precursors as lathosterol and 7-dehydrocholesterol is observed. The formation of cholesterol photooxidation products under the effect of UV-radiation in vivo is shown. The quantitative ratios of sterols under study depend on spectral characteristics of the applied UV-radiation sources. The cholesterol photooxidation products and antirachitic compounds formed in skin under the effect of UV-radiation are supposed to take part in inhibition of cholesterol biosynthesis."} {"id": "PMID:1258166", "title": "[Study of interaction between alcohols (mono- and polhydric) and proteins in aqueous solutions].", "content": "Phosphorescence properties of protein aqueous solutions (life-time, bend-point on the plots of life-time v. s. temperature, maximum positions in spectra, intensity) were shown to depend upon the concentration in the solution of solute--additions (mono- and polyhydric alcohols, glucose, sucrose, certain amino acids). New parameter tau--average life-time of protein phosphorescence in the persence in the solution of the iodine ion constant concentration, was proposed. By the character of dependence of this parameter upon the solute-addition concentration all solutes, which were used as additions, may be devided into two classes. A rise in the solution of the first class additions (monohydric alcohols) was followed by an increase of tau, that evidences for a decrease in availability of protein tryptophanyls, which may be a result of the adsorption of solute-addition by protein. With the addition concentration about 0.5% tau passes through maximum and then decreases. An increase in the solution of the second class addition (glycol, glycerol, polyethylenglycol, glucose, surcrose) was followed by a decrease of tau, that indicates to an increase of trypophanyl availability, Such an interaction of additions with protein is typical of papain and fibrinogen. In the case of myosin the addition of the second class solutes causes a sharp increase of tau with their sufficient concentration. The obtained results make it possible to state that the solute-additions affect proteins directly besides their indirect influence by a change in the water structure.", "contents": "[Study of interaction between alcohols (mono- and polhydric) and proteins in aqueous solutions]. Phosphorescence properties of protein aqueous solutions (life-time, bend-point on the plots of life-time v. s. temperature, maximum positions in spectra, intensity) were shown to depend upon the concentration in the solution of solute--additions (mono- and polyhydric alcohols, glucose, sucrose, certain amino acids). New parameter tau--average life-time of protein phosphorescence in the persence in the solution of the iodine ion constant concentration, was proposed. By the character of dependence of this parameter upon the solute-addition concentration all solutes, which were used as additions, may be devided into two classes. A rise in the solution of the first class additions (monohydric alcohols) was followed by an increase of tau, that evidences for a decrease in availability of protein tryptophanyls, which may be a result of the adsorption of solute-addition by protein. With the addition concentration about 0.5% tau passes through maximum and then decreases. An increase in the solution of the second class addition (glycol, glycerol, polyethylenglycol, glucose, surcrose) was followed by a decrease of tau, that indicates to an increase of trypophanyl availability, Such an interaction of additions with protein is typical of papain and fibrinogen. In the case of myosin the addition of the second class solutes causes a sharp increase of tau with their sufficient concentration. The obtained results make it possible to state that the solute-additions affect proteins directly besides their indirect influence by a change in the water structure."} {"id": "PMID:1258226", "title": "[The neutropathic urethra: urethrogram and pathophysiologic aspects (author's transl)].", "content": "In the analysis of neurogenic urinary voiding disturbances, too much attention has been paid to the bladder, too little to the muscular tubing of the posterior urethra and to the pelvic floor. Contrast radiography of the urethra in injection and micturition, combined with urodynamic investigations, seemed suitable for comprehension of neurogenic functional disturbances of the posterior urethra and the pelvic floor. A cross section of 143 predominantly traumatic patients and 69 patients with myelomeningocele were investigated radiologically. In addition, in a number of patients urinary flow was determined by uroflowmetry and micturition studies with simultaneous recording of intravesical and intrarectal pressure, of the EMG-activity of the pelvic floor and urinary flow were performed by a special method. The radiologic section (I) shows that the urinary picture of various neurogenic bladder types are characterized by specific changes in form of the posterior urethra. With the help of systematic investigations of a number of cases it was demonstrated that in automatic bladder the roentgen contour of the urethra changes with duration of illness and that primarily secondary, morphologic changes-recognizable at the same time from the increasing number of radiologically demonstrable changes of the prostate and the seminal vesicles-are responsible. Simultaneously a typical deformation of the posterior urethra in passive urinary voiding is described, and attention directed to the fact that the urinary pictures of children with neurogenic impaired urethra sometimes cannot be distinguished from those with urethral values. Urinary flow measurements (II) show that the flow rates from a cross section of patients with lesions of the upper and lower neurons are significantly lower in comparison to normals. With the help of combined urodynamic investigations (III) it was demonstrated that a functional obstruction was present in the neurogenic bladder at the level of spastic and of paretic pelvic floors. It was proved that the roentgenologically visible deformation of the posterior urethra plays a quite decisive role in neurogenically disturbed urinary voiding. It is the main reason why, despite sufficient bladder pressure values, urinary voiding remains unsatisfactory and urinary performance low. Hence the therapeutic consequence follows: an improvement in urinary performance in neurogenic bladder is generally only possible through a decrease in the expulsion resistance. Various operative procedures for the release of bladder outlet obstruction and their uses are discussed.", "contents": "[The neutropathic urethra: urethrogram and pathophysiologic aspects (author's transl)]. In the analysis of neurogenic urinary voiding disturbances, too much attention has been paid to the bladder, too little to the muscular tubing of the posterior urethra and to the pelvic floor. Contrast radiography of the urethra in injection and micturition, combined with urodynamic investigations, seemed suitable for comprehension of neurogenic functional disturbances of the posterior urethra and the pelvic floor. A cross section of 143 predominantly traumatic patients and 69 patients with myelomeningocele were investigated radiologically. In addition, in a number of patients urinary flow was determined by uroflowmetry and micturition studies with simultaneous recording of intravesical and intrarectal pressure, of the EMG-activity of the pelvic floor and urinary flow were performed by a special method. The radiologic section (I) shows that the urinary picture of various neurogenic bladder types are characterized by specific changes in form of the posterior urethra. With the help of systematic investigations of a number of cases it was demonstrated that in automatic bladder the roentgen contour of the urethra changes with duration of illness and that primarily secondary, morphologic changes-recognizable at the same time from the increasing number of radiologically demonstrable changes of the prostate and the seminal vesicles-are responsible. Simultaneously a typical deformation of the posterior urethra in passive urinary voiding is described, and attention directed to the fact that the urinary pictures of children with neurogenic impaired urethra sometimes cannot be distinguished from those with urethral values. Urinary flow measurements (II) show that the flow rates from a cross section of patients with lesions of the upper and lower neurons are significantly lower in comparison to normals. With the help of combined urodynamic investigations (III) it was demonstrated that a functional obstruction was present in the neurogenic bladder at the level of spastic and of paretic pelvic floors. It was proved that the roentgenologically visible deformation of the posterior urethra plays a quite decisive role in neurogenically disturbed urinary voiding. It is the main reason why, despite sufficient bladder pressure values, urinary voiding remains unsatisfactory and urinary performance low. Hence the therapeutic consequence follows: an improvement in urinary performance in neurogenic bladder is generally only possible through a decrease in the expulsion resistance. Various operative procedures for the release of bladder outlet obstruction and their uses are discussed."} {"id": "PMID:1258227", "title": "[Transretcat aspiration biopsy in the diagnosis of prostatic cancer (author's transl)].", "content": "In almost three years 853 prostatic aspirates obtained from 709 patients were cytologically examined. In 313 patients we also made histological examinations. The cytologic diagnosis could be checked by histology in 288 untreated patients. The cytologic diagnosis of prostatic cancer was confirmed by histology in 65.3% and was false negative in 28.3%. In 6.4% the cytologic material was unsatisfactory for cytologic examination. Considering cytologic findings after repeat aspiration biopsy the accuracy of the cytologic method was 71.7%. The detection rate of prostatic cancer is about 20% higher using both, cytologic and histologic methods, than using cytology or histology, only.", "contents": "[Transretcat aspiration biopsy in the diagnosis of prostatic cancer (author's transl)]. In almost three years 853 prostatic aspirates obtained from 709 patients were cytologically examined. In 313 patients we also made histological examinations. The cytologic diagnosis could be checked by histology in 288 untreated patients. The cytologic diagnosis of prostatic cancer was confirmed by histology in 65.3% and was false negative in 28.3%. In 6.4% the cytologic material was unsatisfactory for cytologic examination. Considering cytologic findings after repeat aspiration biopsy the accuracy of the cytologic method was 71.7%. The detection rate of prostatic cancer is about 20% higher using both, cytologic and histologic methods, than using cytology or histology, only."} {"id": "PMID:1258228", "title": "[The role of cells originating from seminal vesicles in aspiration biopsy smears of the prostate (author's transl)].", "content": "328 (30.7%) of 1068 prostatic aspirates obtained from 874 patients contained cells of seminal vesicle origin. Cells originating from the seminal vesicles were recognized in aspirates obtained from 27.6% of the untreated patients and in aspirates from 60.4% of the treated patients. Patients of the latter group had received hormonal treatment or radation therapy, or both, or had been surgically treated by prostatectomy. The occurrence of cells derived from seminal vesicles was due to the site of the needled prostatic lesion in 21% of the aspirates obtained, to treatment in 21% and to incorrect biopsy technique in the remaining 58%. A false cytologic report was made in the case of 6 aspirates (1.6%).", "contents": "[The role of cells originating from seminal vesicles in aspiration biopsy smears of the prostate (author's transl)]. 328 (30.7%) of 1068 prostatic aspirates obtained from 874 patients contained cells of seminal vesicle origin. Cells originating from the seminal vesicles were recognized in aspirates obtained from 27.6% of the untreated patients and in aspirates from 60.4% of the treated patients. Patients of the latter group had received hormonal treatment or radation therapy, or both, or had been surgically treated by prostatectomy. The occurrence of cells derived from seminal vesicles was due to the site of the needled prostatic lesion in 21% of the aspirates obtained, to treatment in 21% and to incorrect biopsy technique in the remaining 58%. A false cytologic report was made in the case of 6 aspirates (1.6%)."} {"id": "PMID:1258229", "title": "[Nuclear medical techniques in diagnostics of urological diseases (author's transl)].", "content": "We report on the evaluation of 2170 kidney scintigrams and isotope nephrograms under the aspect of a urological radiodiagnostic of the kidney. The possibilities of a nuclear medical demonstration for kidney tumours are discussed. Furthermore we refer to the importance of the isotope nephrogram to recognize intermitting obstructions of the ureters.", "contents": "[Nuclear medical techniques in diagnostics of urological diseases (author's transl)]. We report on the evaluation of 2170 kidney scintigrams and isotope nephrograms under the aspect of a urological radiodiagnostic of the kidney. The possibilities of a nuclear medical demonstration for kidney tumours are discussed. Furthermore we refer to the importance of the isotope nephrogram to recognize intermitting obstructions of the ureters."} {"id": "PMID:1258230", "title": "[Postrenal amuria in polycystic degeneration of a residual kidney (author's transl)].", "content": "A case of a residual kidney and polycystic renal degeneration is reported in which postrenal anuria developed from a cluster of cysts filling the entire renal pelvis. The anuria was repired by removing the intrapelvic cysts and creating a temporary renal fistula. A sudden onset of anuria and the corresponding symptoms (e.g., acute abdominal pain) and also the familiar progressive polycystic degeneration of the kidney should arouse suspicion of an obstruction caused by cysts.", "contents": "[Postrenal amuria in polycystic degeneration of a residual kidney (author's transl)]. A case of a residual kidney and polycystic renal degeneration is reported in which postrenal anuria developed from a cluster of cysts filling the entire renal pelvis. The anuria was repired by removing the intrapelvic cysts and creating a temporary renal fistula. A sudden onset of anuria and the corresponding symptoms (e.g., acute abdominal pain) and also the familiar progressive polycystic degeneration of the kidney should arouse suspicion of an obstruction caused by cysts."} {"id": "PMID:1258231", "title": "[The dangers of antibiotic therapy in gram-negative pathogens (author's transl)].", "content": "The increased occurrence of so-called gram-negative problem bacteria in urology compels us to use highly effective antibiotics in optimal doses. The danger of such therapy is illustrated by three cases in whom toxic damage was demonstrated following combined treatment with aminoglycosides and cephalosporins.", "contents": "[The dangers of antibiotic therapy in gram-negative pathogens (author's transl)]. The increased occurrence of so-called gram-negative problem bacteria in urology compels us to use highly effective antibiotics in optimal doses. The danger of such therapy is illustrated by three cases in whom toxic damage was demonstrated following combined treatment with aminoglycosides and cephalosporins."} {"id": "PMID:1258232", "title": "[The bifid ureter with a blind-ending branch -- its clinical problematic (author's transl)].", "content": "The symptoms and clinical significance of the bifid ureter with a blind-ending branch are presented. A uretero-ureteral reflux is the pathophysiologic pre-condition for the disease and its diagnosis. Complaints arise from recurrent urinary infection and/or dilatation of the blind end.", "contents": "[The bifid ureter with a blind-ending branch -- its clinical problematic (author's transl)]. The symptoms and clinical significance of the bifid ureter with a blind-ending branch are presented. A uretero-ureteral reflux is the pathophysiologic pre-condition for the disease and its diagnosis. Complaints arise from recurrent urinary infection and/or dilatation of the blind end."} {"id": "PMID:1258234", "title": "Operative and nonoperative hypertension. Recent advances in treatment.", "content": "In the past five years there have been significant advances in the diagnosis and treatment of operative and nonoperative forms of hypertension. Several areas of specific interest to urologists will be discussed.", "contents": "Operative and nonoperative hypertension. Recent advances in treatment. In the past five years there have been significant advances in the diagnosis and treatment of operative and nonoperative forms of hypertension. Several areas of specific interest to urologists will be discussed."} {"id": "PMID:1258235", "title": "Complications of renal cyst exploration versus renal mass aspiration.", "content": "This report presents a comparison of the complications of surgical exploration with unroofing and renal cyst puncture. Two hundred fifty-five patients were operated on, with a mortality rate of 1 per cent and a morbidity rate of 28 per cent. The complications in 63 patients examined by mass aspiration included a morbidity rate of 6.4 per cent and no mortality. The possibilities of over-looking carcinomas through cyst aspiration are weighed against the demonstrated morbidity of surgical exploration and found to be much less significant. The authors recommend that an asymptomatic renal mass that radiographically appears to be a cyst and is unaccompanied by urine changes or clinical stigmata of renal neoplasia be treated by cyst aspiration and not subjected to surgical exploration.", "contents": "Complications of renal cyst exploration versus renal mass aspiration. This report presents a comparison of the complications of surgical exploration with unroofing and renal cyst puncture. Two hundred fifty-five patients were operated on, with a mortality rate of 1 per cent and a morbidity rate of 28 per cent. The complications in 63 patients examined by mass aspiration included a morbidity rate of 6.4 per cent and no mortality. The possibilities of over-looking carcinomas through cyst aspiration are weighed against the demonstrated morbidity of surgical exploration and found to be much less significant. The authors recommend that an asymptomatic renal mass that radiographically appears to be a cyst and is unaccompanied by urine changes or clinical stigmata of renal neoplasia be treated by cyst aspiration and not subjected to surgical exploration."} {"id": "PMID:1258236", "title": "Simplified operative nephroscopy.", "content": "Intraoperative nephroscopy is a valuable and practical adjunct to renal surgery. A simplified methodology is described using familiar cystoscopic equipment and techniques. Its particular usefulness in the definition of small radiolucent defects of the renal collecting system is illustrated.", "contents": "Simplified operative nephroscopy. Intraoperative nephroscopy is a valuable and practical adjunct to renal surgery. A simplified methodology is described using familiar cystoscopic equipment and techniques. Its particular usefulness in the definition of small radiolucent defects of the renal collecting system is illustrated."} {"id": "PMID:1258237", "title": "Management of postoperative fistula of upper urinary tract.", "content": "The simple procedure of passage and withdrawal of a ureteral catheter hastens the closure of a urinary fistula after surgery of the ureter or renal pelvis.", "contents": "Management of postoperative fistula of upper urinary tract. The simple procedure of passage and withdrawal of a ureteral catheter hastens the closure of a urinary fistula after surgery of the ureter or renal pelvis."} {"id": "PMID:1258238", "title": "Absence of vesicoureteral reflux after stone basket manipulation. Reflections on iatrogenic reflux.", "content": "Twenty-four patients were studied after cystoscopic basket manipulation for distal ureteral calculi. Voiding cystourethrograms or cystograms were obtained at varying intervals post-operatively to detect evidence of vesicoureteral reflux. Reflux did not develop in any of the patients. In comparison with other known causes of iatrogenic reflux, stone basket manipulation does not appear to interfere with anatomic factors which normally prevent incompetence of the ureterovesical valvular mechanism.", "contents": "Absence of vesicoureteral reflux after stone basket manipulation. Reflections on iatrogenic reflux. Twenty-four patients were studied after cystoscopic basket manipulation for distal ureteral calculi. Voiding cystourethrograms or cystograms were obtained at varying intervals post-operatively to detect evidence of vesicoureteral reflux. Reflux did not develop in any of the patients. In comparison with other known causes of iatrogenic reflux, stone basket manipulation does not appear to interfere with anatomic factors which normally prevent incompetence of the ureterovesical valvular mechanism."} {"id": "PMID:1258239", "title": "Reflux in opposite ureter after successful correction of unilateral vesicoureteral reflux.", "content": "Reflux developed in the contralateral ureter in 20 per cent of our patients undergoing unilateral ureteral reimplantation for reflux. This occurrence was not predictable from the preoperative evaluation. Bilateral reimplantation may be indicated in some patients requiring surgical correction for demonstrated reflux.", "contents": "Reflux in opposite ureter after successful correction of unilateral vesicoureteral reflux. Reflux developed in the contralateral ureter in 20 per cent of our patients undergoing unilateral ureteral reimplantation for reflux. This occurrence was not predictable from the preoperative evaluation. Bilateral reimplantation may be indicated in some patients requiring surgical correction for demonstrated reflux."} {"id": "PMID:1258241", "title": "Effect of furosemide on postprostatectomy blood loss.", "content": "The value of induced diuresis, employing furosemide, on blood loss during and after prostatectomy is evaluated. Two series of 100 patients (consecutive) undergoing prostatectomy, one series with furosemide and one without, are compared. The conclusion drawn from critical analysis is that induced diuresis with furosemide is beneficial in reducing blood loss.", "contents": "Effect of furosemide on postprostatectomy blood loss. The value of induced diuresis, employing furosemide, on blood loss during and after prostatectomy is evaluated. Two series of 100 patients (consecutive) undergoing prostatectomy, one series with furosemide and one without, are compared. The conclusion drawn from critical analysis is that induced diuresis with furosemide is beneficial in reducing blood loss."} {"id": "PMID:1258242", "title": "Changes in testis of guinea pig after vasectomy.", "content": "Thirty adult guinea pigs were bilaterally vasectomized and subsequently sacrificed at one, three, and six months after operation. Cell counts were performed on five seminiferous tubules from each animal to identify and quantitate changes in spermatogenesis. Forty-three per cent of the animals had alterations in spermatogenesis that were characterized by generalized hypospermatogenesis and presence of multinucleated spermatids. There was a high incidence (93 per cent) of sperm-agglutinating antibodies in the vasectomized group. Sperm antibodies were not detected in the normal and sham-operated animals. Mean testicular weights and seminiferous tubule diameters were significantly reduced in the hypospermatogenic animals. The intersitial tissue of the vasectomized and sham-operated animals was morphologically indistinguishable from that of unoperated animals.", "contents": "Changes in testis of guinea pig after vasectomy. Thirty adult guinea pigs were bilaterally vasectomized and subsequently sacrificed at one, three, and six months after operation. Cell counts were performed on five seminiferous tubules from each animal to identify and quantitate changes in spermatogenesis. Forty-three per cent of the animals had alterations in spermatogenesis that were characterized by generalized hypospermatogenesis and presence of multinucleated spermatids. There was a high incidence (93 per cent) of sperm-agglutinating antibodies in the vasectomized group. Sperm antibodies were not detected in the normal and sham-operated animals. Mean testicular weights and seminiferous tubule diameters were significantly reduced in the hypospermatogenic animals. The intersitial tissue of the vasectomized and sham-operated animals was morphologically indistinguishable from that of unoperated animals."} {"id": "PMID:1258243", "title": "Prevention of infection during transrectal biopsy of prostate through double-glove technique.", "content": "Eighty male patients, most of whom had suspicious prostatic nodules on digital examination, were subjected to transrectal needle biopsy of the prostate. The biopsy needle was held between the gloved hand and an overlying sterile finger cot on the index finger. When the lesion was palpated, the needle was pushed through the finger cot and a tissue specimen obtained. All patients were treated orally with minocycline hydrochloride 100 mg. twice a day starting eight to twelve hours before biopsy and continuing at this dosage for five days after biopsy. Except for one episode of transitory hematuria, there were no reports of infection or complication, as manifested by fever, chills, or transrectal or transurethral bleeding.", "contents": "Prevention of infection during transrectal biopsy of prostate through double-glove technique. Eighty male patients, most of whom had suspicious prostatic nodules on digital examination, were subjected to transrectal needle biopsy of the prostate. The biopsy needle was held between the gloved hand and an overlying sterile finger cot on the index finger. When the lesion was palpated, the needle was pushed through the finger cot and a tissue specimen obtained. All patients were treated orally with minocycline hydrochloride 100 mg. twice a day starting eight to twelve hours before biopsy and continuing at this dosage for five days after biopsy. Except for one episode of transitory hematuria, there were no reports of infection or complication, as manifested by fever, chills, or transrectal or transurethral bleeding."} {"id": "PMID:1258244", "title": "Regression of pulmonary metastases from renal carcinoma.", "content": "This article describes a patient who had a nephrectomy and hormone therapy for renal carcinoma. There was roentgenographic evidence of pulmonary metastases at the time of surgery. He was alive and showed no clinical or roentgenographic evidence of pulmonary metastases six and one-half years after treatment.", "contents": "Regression of pulmonary metastases from renal carcinoma. This article describes a patient who had a nephrectomy and hormone therapy for renal carcinoma. There was roentgenographic evidence of pulmonary metastases at the time of surgery. He was alive and showed no clinical or roentgenographic evidence of pulmonary metastases six and one-half years after treatment."} {"id": "PMID:1258245", "title": "Testis tumor metastatic to lung: twenty-two-year survivor.", "content": "A case is presented of a twenty-two-year survivor following pulmonary resection of a solitary embryonal cell carcinoma metastasis from a primary teratocarcinoma of the testis. The literature is reviewed with regard to this problem, and the criteria for pulmonary resection of metastic lesions are presented.", "contents": "Testis tumor metastatic to lung: twenty-two-year survivor. A case is presented of a twenty-two-year survivor following pulmonary resection of a solitary embryonal cell carcinoma metastasis from a primary teratocarcinoma of the testis. The literature is reviewed with regard to this problem, and the criteria for pulmonary resection of metastic lesions are presented."} {"id": "PMID:1258246", "title": "Arteriovenous aneurysm of kidney after open renal biopsy.", "content": "Renal arteriovenous fistula following percutaneous renal biopsy is being reported frequently in the literature. For this reason, open renal biopsy has gained popularity as a safer alternative procedure. We present a case of a large arteriovenous fistula seen two years after open renal biopsy. The presentation was highly atypical, mimicking an acute gastrointestinal event, rather than sudden hemorrhage in a previously asymptomatic fistula.", "contents": "Arteriovenous aneurysm of kidney after open renal biopsy. Renal arteriovenous fistula following percutaneous renal biopsy is being reported frequently in the literature. For this reason, open renal biopsy has gained popularity as a safer alternative procedure. We present a case of a large arteriovenous fistula seen two years after open renal biopsy. The presentation was highly atypical, mimicking an acute gastrointestinal event, rather than sudden hemorrhage in a previously asymptomatic fistula."} {"id": "PMID:1258247", "title": "Characterization of renal stone models with Gray Scale echography. In vitro studies with clinical correlation.", "content": "Solid, matrix, and urate stone models were studied in an idealized laboratory setting by gray scale echography. The stone models could be both identified and characterized by ultrasound. Preliminary studies indicate that ultrasound may be useful in determining the nature of foreign matter in the collecting systems of patients with renal calculous disease.", "contents": "Characterization of renal stone models with Gray Scale echography. In vitro studies with clinical correlation. Solid, matrix, and urate stone models were studied in an idealized laboratory setting by gray scale echography. The stone models could be both identified and characterized by ultrasound. Preliminary studies indicate that ultrasound may be useful in determining the nature of foreign matter in the collecting systems of patients with renal calculous disease."} {"id": "PMID:1258250", "title": "Postoperative nephrogenic adenoma of bladder.", "content": "Nephrogenic adenoma of the bladder, which has been associated with either a chronic infection or severe trauma to the bladder, occurred in a six-year-old girl apparently secondary to urologic surgery. It was also a possible cause of enuresis.", "contents": "Postoperative nephrogenic adenoma of bladder. Nephrogenic adenoma of the bladder, which has been associated with either a chronic infection or severe trauma to the bladder, occurred in a six-year-old girl apparently secondary to urologic surgery. It was also a possible cause of enuresis."} {"id": "PMID:1258280", "title": "Paraquat poisoning in a dog and cat.", "content": "Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) has in the last decade gained popularity as an effective weedicide. It is marketed for commercial use as a liquid concentrate Gramoxone ICI (20% paraquat). Accidental or intentional ingestion of Gramoxone has caused 232 human deaths between 1964 and 1973 (Anon 1974). Most human patients suffer transient renal and hepatic insufficiency and pulmonary oedema followed after a latent period by progressive pulmonary fibrosis leading to death from respiratory failure (Harrison 1972). The clinical features of non-fatal paraquet poisoning in a cat and the clinical and pathological findings in fatal poisoning in a dog are reported.", "contents": "Paraquat poisoning in a dog and cat. Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) has in the last decade gained popularity as an effective weedicide. It is marketed for commercial use as a liquid concentrate Gramoxone ICI (20% paraquat). Accidental or intentional ingestion of Gramoxone has caused 232 human deaths between 1964 and 1973 (Anon 1974). Most human patients suffer transient renal and hepatic insufficiency and pulmonary oedema followed after a latent period by progressive pulmonary fibrosis leading to death from respiratory failure (Harrison 1972). The clinical features of non-fatal paraquet poisoning in a cat and the clinical and pathological findings in fatal poisoning in a dog are reported."} {"id": "PMID:1258288", "title": "Porcine atrophic rhinitis: snout radiography as an aid to diagnosis and detection of the disease.", "content": "Snout radiography is a useful and practicable aid to the diagnosis of atrophic rhinitis. It is also a fairly reliable means of detecting and measuring turbinate atrophy and distortion of the septum nasi in the live pig. Suitable physical and pharmacological methods of restraining pigs for snout radiography are described and guide lines for producing satisfactory, standard snout radiographs are given. Parameters and criteria are recommended for qualitative and quantitative methods of interpreting snout radiographs. The quantitative scoring system approximates the macroscopic post mortem snout scoring system generally employed in Britain and provides data which might be used in genetic or other control programmes. Radiographic standards are tentatively suggested for certifying pigs free from gross lesions of atrophic rhinitis for sale or export purposes.", "contents": "Porcine atrophic rhinitis: snout radiography as an aid to diagnosis and detection of the disease. Snout radiography is a useful and practicable aid to the diagnosis of atrophic rhinitis. It is also a fairly reliable means of detecting and measuring turbinate atrophy and distortion of the septum nasi in the live pig. Suitable physical and pharmacological methods of restraining pigs for snout radiography are described and guide lines for producing satisfactory, standard snout radiographs are given. Parameters and criteria are recommended for qualitative and quantitative methods of interpreting snout radiographs. The quantitative scoring system approximates the macroscopic post mortem snout scoring system generally employed in Britain and provides data which might be used in genetic or other control programmes. Radiographic standards are tentatively suggested for certifying pigs free from gross lesions of atrophic rhinitis for sale or export purposes."} {"id": "PMID:1258296", "title": "An assessment of the practical impact of insecticide resistance.", "content": "In spite of widespread resistance of the sheep blowfly to organophosphorus insecticides, they are still widely relied upon in Austrialia. Hybrid-resistant blowfly larvae do not produce fly-strike as readily as pure-resistant larvae so more attention should be paid to the use of biological, rather than chemical, control, wherever possible.", "contents": "An assessment of the practical impact of insecticide resistance. In spite of widespread resistance of the sheep blowfly to organophosphorus insecticides, they are still widely relied upon in Austrialia. Hybrid-resistant blowfly larvae do not produce fly-strike as readily as pure-resistant larvae so more attention should be paid to the use of biological, rather than chemical, control, wherever possible."} {"id": "PMID:1258301", "title": "Studies in dogs and cats dosed with trimethoprim and sulphadiazine.", "content": "Serum level studies in cats and dogs dosed with 30 mg per kg per day of either oral or injectable formulations of a 1:5 trimethoprim/sulphadiazine combination showed good absorption by both routes of administration. Toxicity tests with the products demonstrated a high margin of safety in dogs given this dose level; the margin of safety in cats was lower but still adequate. The high success rate in clinical trials against a wide range of bacterial infections confirmed the predictions from the serum level results that a dose rate of 30 mg per kg per day orally or parentally, would be therapeutically efficacious in both species.", "contents": "Studies in dogs and cats dosed with trimethoprim and sulphadiazine. Serum level studies in cats and dogs dosed with 30 mg per kg per day of either oral or injectable formulations of a 1:5 trimethoprim/sulphadiazine combination showed good absorption by both routes of administration. Toxicity tests with the products demonstrated a high margin of safety in dogs given this dose level; the margin of safety in cats was lower but still adequate. The high success rate in clinical trials against a wide range of bacterial infections confirmed the predictions from the serum level results that a dose rate of 30 mg per kg per day orally or parentally, would be therapeutically efficacious in both species."} {"id": "PMID:1258302", "title": "Copper metabolism in experimental Border disease.", "content": "The proposal that hypocupraemia and hypocuprosis are characteristic manifestations of Border disease and of aetiological significance has been investigated. Mean plasma copper concentrations in 65 affected and 47 unaffected lambs were similar and in a controlled experiment, plasma and tissue copper concentrations tended to be higher in affected lambs than in controls. It is concluded that hypocupraemia and hypocuprosis are not consistent features of Border disease and thus have no aetiological significance.", "contents": "Copper metabolism in experimental Border disease. The proposal that hypocupraemia and hypocuprosis are characteristic manifestations of Border disease and of aetiological significance has been investigated. Mean plasma copper concentrations in 65 affected and 47 unaffected lambs were similar and in a controlled experiment, plasma and tissue copper concentrations tended to be higher in affected lambs than in controls. It is concluded that hypocupraemia and hypocuprosis are not consistent features of Border disease and thus have no aetiological significance."} {"id": "PMID:1258303", "title": "Bos taurus Y chromosome of Africander cattle and the development of improved breeds for the tropics.", "content": "The Africander has anatomical and other characteristics of an animal of approximately 3/4 Bos indicus heredity. The fact that these cattle carry the Bos taurus Y chromosome supports this view and indicates that the local cattle in South Africa would have been crossed with one or more Bos taurus bulls. Droughtmaster and Braford cattle retain the Bos indicus Y chromosome because Bos indicus instead of Bos taurus bulls were used to establish these taurindicus breeds. Contrary to some assumptions, an approximate tenfold increase in productivity of cattle was made during the 18th and 19th centuries due to improvements in disease control, nutrition and genetic improvement. What is now needed is the development of taurindicus breeds combining to the maximum possible extent the disease resistance and hardiness of Bos indicus with the early maturity and productivity of Bos taurus cattle. In addition, the ravages of disease and the seasonal variations of food supply need to be overcome in tropical areas.", "contents": "Bos taurus Y chromosome of Africander cattle and the development of improved breeds for the tropics. The Africander has anatomical and other characteristics of an animal of approximately 3/4 Bos indicus heredity. The fact that these cattle carry the Bos taurus Y chromosome supports this view and indicates that the local cattle in South Africa would have been crossed with one or more Bos taurus bulls. Droughtmaster and Braford cattle retain the Bos indicus Y chromosome because Bos indicus instead of Bos taurus bulls were used to establish these taurindicus breeds. Contrary to some assumptions, an approximate tenfold increase in productivity of cattle was made during the 18th and 19th centuries due to improvements in disease control, nutrition and genetic improvement. What is now needed is the development of taurindicus breeds combining to the maximum possible extent the disease resistance and hardiness of Bos indicus with the early maturity and productivity of Bos taurus cattle. In addition, the ravages of disease and the seasonal variations of food supply need to be overcome in tropical areas."} {"id": "PMID:1258307", "title": "Salmonellosis in apparently healthy dogs.", "content": "When rectal swabs were examined from 672 dogs in Tehran, Iran, 52 (7-7 per cent) yielded Salmonellae of 20 different serotypes. The 672 dogs examined comprised 472 household pets, 181 kennel dogs and 19 strays. Tehy showed an incidence of 4-4 per cent, 15-5 per cent and 15-8 per cent respectively.", "contents": "Salmonellosis in apparently healthy dogs. When rectal swabs were examined from 672 dogs in Tehran, Iran, 52 (7-7 per cent) yielded Salmonellae of 20 different serotypes. The 672 dogs examined comprised 472 household pets, 181 kennel dogs and 19 strays. Tehy showed an incidence of 4-4 per cent, 15-5 per cent and 15-8 per cent respectively."} {"id": "PMID:1258313", "title": "Intestinal malformations in calves and their surgical correction.", "content": "A clinical study was made on 45 cases of intestinal malformations found in calves during a four year period. Fifteen calves were euthanised for different reasons. Surgical correction was made in 30 calves; 15 of them recovered. The recovery depended on the extent and the localisation of the defect and on the general condition of the animal.", "contents": "Intestinal malformations in calves and their surgical correction. A clinical study was made on 45 cases of intestinal malformations found in calves during a four year period. Fifteen calves were euthanised for different reasons. Surgical correction was made in 30 calves; 15 of them recovered. The recovery depended on the extent and the localisation of the defect and on the general condition of the animal."} {"id": "PMID:1258319", "title": "An investigation into the prevalence of S aureus on avian feet.", "content": "The feet of 63 domestic poultry and 37 birds of prey were swabbed and cultured. Staphylococcus aureus was isolated from 4 X 7 per cent of the former and 10 X 8 per cent of the latter. The recovery of S epidermidis was considerably higher, the organism being cultured from 80 X 9 per cent of poultry and 62 X 1 per cent of birds of prey. The significance of the low S aureus isolation rates is discussed in relation to avian staphylococcal infections and attention is drawn to the importance of the choice of plasma for the coagulase test when identifying S aureus from non-human sources.", "contents": "An investigation into the prevalence of S aureus on avian feet. The feet of 63 domestic poultry and 37 birds of prey were swabbed and cultured. Staphylococcus aureus was isolated from 4 X 7 per cent of the former and 10 X 8 per cent of the latter. The recovery of S epidermidis was considerably higher, the organism being cultured from 80 X 9 per cent of poultry and 62 X 1 per cent of birds of prey. The significance of the low S aureus isolation rates is discussed in relation to avian staphylococcal infections and attention is drawn to the importance of the choice of plasma for the coagulase test when identifying S aureus from non-human sources."} {"id": "PMID:1258349", "title": "[Some physicochemical changes in poultry meat caused by Pseudomonas ssp. II].", "content": "Studies showed that the reproductive capacity and the biochemical activity of the experimental Pseudomonas ssp. II are manifested to a various extent in the white and red poultry meat. No changes in the meat set in until the microbial count reach 10(8)-10(9) per gram of meat. This critical value is reached on the fifth day for the red meat, and the 7th day for the white meat. Later on the changes in PH, the aminoammonia nitrogen, the volatile fatty acids, the ammonia gas reaction, and the CuSO4 reaction show such values that give grounds to discard the meat. The reaction for the demonstration of H2S is consistently negative, which is referred to as an individual feature of the monoculture used.", "contents": "[Some physicochemical changes in poultry meat caused by Pseudomonas ssp. II]. Studies showed that the reproductive capacity and the biochemical activity of the experimental Pseudomonas ssp. II are manifested to a various extent in the white and red poultry meat. No changes in the meat set in until the microbial count reach 10(8)-10(9) per gram of meat. This critical value is reached on the fifth day for the red meat, and the 7th day for the white meat. Later on the changes in PH, the aminoammonia nitrogen, the volatile fatty acids, the ammonia gas reaction, and the CuSO4 reaction show such values that give grounds to discard the meat. The reaction for the demonstration of H2S is consistently negative, which is referred to as an individual feature of the monoculture used."} {"id": "PMID:1258350", "title": "[Effect of ionizing radiation on the activity of liver acid phosphatase in chick embryos and chickens].", "content": "The treatment of chick embryos and chickens at 1000 rad leads to the decrease of the total activity and the increase of the free activity of the acid phosphatase in the liver. These changes are mostly manifested at the 72nd hour following irradiation. The electron-microscopic studies reveal secondary lysozomes (cytolyzomes) full of round or elongated structures of varying density. All changes are most strongly manifested in 12-day-old embryos, and are most weakly manifested in 20-day-old ones.", "contents": "[Effect of ionizing radiation on the activity of liver acid phosphatase in chick embryos and chickens]. The treatment of chick embryos and chickens at 1000 rad leads to the decrease of the total activity and the increase of the free activity of the acid phosphatase in the liver. These changes are mostly manifested at the 72nd hour following irradiation. The electron-microscopic studies reveal secondary lysozomes (cytolyzomes) full of round or elongated structures of varying density. All changes are most strongly manifested in 12-day-old embryos, and are most weakly manifested in 20-day-old ones."} {"id": "PMID:1258352", "title": "[Effect of subtoxic doses of dipterex on guinea pigs].", "content": "Chronic experiments were carried out with 62 guinea pigs (31 test and 31 control animals) which were given dipterex orally for 60 days at the rate of 100 mg/kg each. The effect was followed up of dipterex on the bactericidal properties of the blood, the phagocytic activity of some organs of the reticulo-endothelial system, the serum cholinesterase, the alkaline phosphatase, the hemoglobin and hematocrit values of the blood, and the proteinogram of the blood serum. A neglible drop of the gamma-globin fraction of the serum and the phagocytic activity of the immobile cells of the RES of the spleen and liver was found. The hemoglobin content decreased by 13.5 per cent, while the hematocrit value remained unchanged. At the amount given above dipterex suppressed by 50 per cent the activity of the serum cholinesterase, and increased by 36 per cent that of the alkaline phosphatase.", "contents": "[Effect of subtoxic doses of dipterex on guinea pigs]. Chronic experiments were carried out with 62 guinea pigs (31 test and 31 control animals) which were given dipterex orally for 60 days at the rate of 100 mg/kg each. The effect was followed up of dipterex on the bactericidal properties of the blood, the phagocytic activity of some organs of the reticulo-endothelial system, the serum cholinesterase, the alkaline phosphatase, the hemoglobin and hematocrit values of the blood, and the proteinogram of the blood serum. A neglible drop of the gamma-globin fraction of the serum and the phagocytic activity of the immobile cells of the RES of the spleen and liver was found. The hemoglobin content decreased by 13.5 per cent, while the hematocrit value remained unchanged. At the amount given above dipterex suppressed by 50 per cent the activity of the serum cholinesterase, and increased by 36 per cent that of the alkaline phosphatase."} {"id": "PMID:1258353", "title": "[Experiments to determine the immunizing dosages in a single vaccinal dose of dried, lapinized K vaccine against swine plague].", "content": "Investigated was the amount of the immunizing doses per one vaccinal pig dose of five operative numbers of the lapinized K vaccine against swine fever. For this purpose pigs were immunized with 100, 200, 300, 400, and 500 fold dilutions of the vaccinal dose. A couple of weeks later the pigs were infected with 10(6)LD50 each of a pathogenic swine fever virus. It was found that the immunizing doses for the individual operative numbers of the vaccine vary in number from 100 to 400 in one vaccinal dose.", "contents": "[Experiments to determine the immunizing dosages in a single vaccinal dose of dried, lapinized K vaccine against swine plague]. Investigated was the amount of the immunizing doses per one vaccinal pig dose of five operative numbers of the lapinized K vaccine against swine fever. For this purpose pigs were immunized with 100, 200, 300, 400, and 500 fold dilutions of the vaccinal dose. A couple of weeks later the pigs were infected with 10(6)LD50 each of a pathogenic swine fever virus. It was found that the immunizing doses for the individual operative numbers of the vaccine vary in number from 100 to 400 in one vaccinal dose."} {"id": "PMID:1258354", "title": "[Study of disorders in calcium and phosphorus metabolism in the intensive fattening of young cattle].", "content": "Studied were mass disease outbreaks on eight farms in calves intensively fed concentrate mixtures that were rich in phosphorus compounds. Clinically, there were selling and deformations of the joints with pains. The tarsal and carpal joints were chiefly involved. Kyphosis of the backbone, spastic paresis of the posterior part of the body as well as tetaniform spasms in the initial stage of the disease were also observed. Morphologically, the diseased animals manifested erosions and thinning of the joint cartilage, tearing of the Achilles tendon, and increased amounts of the joint fluid. The histologic study revealed edema of the cartilage cells, disorders in the structure of the hyalin cartilage, formation of cavities, and broadening of the lumen of the Haversian canals. In most cases the blood serum presented hyperphosphatemia (up to 15.67 mg% inorganic P) and relative or absolute hypocalcemia (up to 4.47 mg% Ca). On the farm both hypocalcemia and hypophosphatemia were observed. Good prophylactic results were obtained through correct Ca:P ratios in the diet that contained calcium additives as well as by the injection of vitamin D solutions, etc. It is believed that these cases should be referred to a distinctive form of rickets of a characteristic clinical course' the inadequate Ca:P ratios in the rations playing the main etiologic role. Subsidiary causes are probably vitamin D deficiency, restricted movement of the animals, and mechanical traumata caused by the animal's own bodyweight.", "contents": "[Study of disorders in calcium and phosphorus metabolism in the intensive fattening of young cattle]. Studied were mass disease outbreaks on eight farms in calves intensively fed concentrate mixtures that were rich in phosphorus compounds. Clinically, there were selling and deformations of the joints with pains. The tarsal and carpal joints were chiefly involved. Kyphosis of the backbone, spastic paresis of the posterior part of the body as well as tetaniform spasms in the initial stage of the disease were also observed. Morphologically, the diseased animals manifested erosions and thinning of the joint cartilage, tearing of the Achilles tendon, and increased amounts of the joint fluid. The histologic study revealed edema of the cartilage cells, disorders in the structure of the hyalin cartilage, formation of cavities, and broadening of the lumen of the Haversian canals. In most cases the blood serum presented hyperphosphatemia (up to 15.67 mg% inorganic P) and relative or absolute hypocalcemia (up to 4.47 mg% Ca). On the farm both hypocalcemia and hypophosphatemia were observed. Good prophylactic results were obtained through correct Ca:P ratios in the diet that contained calcium additives as well as by the injection of vitamin D solutions, etc. It is believed that these cases should be referred to a distinctive form of rickets of a characteristic clinical course' the inadequate Ca:P ratios in the rations playing the main etiologic role. Subsidiary causes are probably vitamin D deficiency, restricted movement of the animals, and mechanical traumata caused by the animal's own bodyweight."} {"id": "PMID:1258355", "title": "[Distribution and seasonal dynamics of Hyalomma plumbeum (Panzer) species ticks in Pazsrdzhik District].", "content": "Determined were specifially a total of 12,580 Ixodes ticks taken from various farm animals. The seasonal dynamics of the parasites were followed up studying the infection in the farm animals in four communities of the Pazardjik district. It was established that from 50.7 to 60.02 per cent of the ticks belong to the Hyalomma plumbeum species. These parasites were found in 45 communities on the territory of the district excluding its southern high mountainous parts. The H. plumbeum infection in farm animals was found from April to November. Most active and numerous were the parasites in June. In the regions of highest altitudes they were prevailing in July.", "contents": "[Distribution and seasonal dynamics of Hyalomma plumbeum (Panzer) species ticks in Pazsrdzhik District]. Determined were specifially a total of 12,580 Ixodes ticks taken from various farm animals. The seasonal dynamics of the parasites were followed up studying the infection in the farm animals in four communities of the Pazardjik district. It was established that from 50.7 to 60.02 per cent of the ticks belong to the Hyalomma plumbeum species. These parasites were found in 45 communities on the territory of the district excluding its southern high mountainous parts. The H. plumbeum infection in farm animals was found from April to November. Most active and numerous were the parasites in June. In the regions of highest altitudes they were prevailing in July."} {"id": "PMID:1258441", "title": "[A comparative assessment of the results of plastic surgery on the facial nerve following total removal of neurinomas of the acoustic nerve].", "content": "The study was conducted in 3 patients following the application of intracranial facial nerve anastomoses, in 25 patients with the facial nerve anastomosed with the accessory nerve, and in 17 patients with facial-hypoglossal nerve anastomoses. Apart from the clinical observations of the facial muscle contractions, the comparative evaluation of the plastic operations was conducted with the aid of electromyography, electrogustometry and salivary glands secretion studies. The authors concluded that the intracranial anastomosis results in better restoration of the motor function of the facial muscles, the gustation being also partially restored on the side on the intervention. Among the anastomoses of the VII nerve with the XII and XI that with the XII is preferred.", "contents": "[A comparative assessment of the results of plastic surgery on the facial nerve following total removal of neurinomas of the acoustic nerve]. The study was conducted in 3 patients following the application of intracranial facial nerve anastomoses, in 25 patients with the facial nerve anastomosed with the accessory nerve, and in 17 patients with facial-hypoglossal nerve anastomoses. Apart from the clinical observations of the facial muscle contractions, the comparative evaluation of the plastic operations was conducted with the aid of electromyography, electrogustometry and salivary glands secretion studies. The authors concluded that the intracranial anastomosis results in better restoration of the motor function of the facial muscles, the gustation being also partially restored on the side on the intervention. Among the anastomoses of the VII nerve with the XII and XI that with the XII is preferred."} {"id": "PMID:1258442", "title": "[Electroencephalographic reflection of arterial spasm following surgery for saccular cerebral aneurysms].", "content": "The purpose of the investigation was to study the electrophysiological manifestations of arterial spasm developing following surgical interventions for cerebral arterial aneurysms. Repeated EEG-recording was undertaken for this purpose in 40 patients with aneurysms of different localization. The EEG data were compared with the results of a neurological examination and angiography performed pre- and postoperatively. It was found that with an uneventful postoperative course no focal changes develop in the bioelectrical activity, and EEG returns to the initial (preoperative) state or to the normal pattern as soon as by the 15th-20th day. In the presence of postoperative arterial spasm, verified clinically and angiographically, the latter is reflected in EEG tracings as peculiar focal changes in the biopotentials. These changes have a nature of a periodically occurring delta-activity recorded predominantly in the zone of ischaemia. Along with a regress of the spasm its EEG manifestations were found to decrease as well. The focal EEG changes observed in postoperative spasm differ from the localization of those EGG changes that are caused by other factors (haematoma, cicatrical processes, etc.).", "contents": "[Electroencephalographic reflection of arterial spasm following surgery for saccular cerebral aneurysms]. The purpose of the investigation was to study the electrophysiological manifestations of arterial spasm developing following surgical interventions for cerebral arterial aneurysms. Repeated EEG-recording was undertaken for this purpose in 40 patients with aneurysms of different localization. The EEG data were compared with the results of a neurological examination and angiography performed pre- and postoperatively. It was found that with an uneventful postoperative course no focal changes develop in the bioelectrical activity, and EEG returns to the initial (preoperative) state or to the normal pattern as soon as by the 15th-20th day. In the presence of postoperative arterial spasm, verified clinically and angiographically, the latter is reflected in EEG tracings as peculiar focal changes in the biopotentials. These changes have a nature of a periodically occurring delta-activity recorded predominantly in the zone of ischaemia. Along with a regress of the spasm its EEG manifestations were found to decrease as well. The focal EEG changes observed in postoperative spasm differ from the localization of those EGG changes that are caused by other factors (haematoma, cicatrical processes, etc.)."} {"id": "PMID:1258443", "title": "[Treatment of aneurysms of the cerebral arteries using stereotaxically oriented external uniform magnetic fields].", "content": "The paper presents a theoretical substantiation of the magnet-haemodynamic method of induced thrombosis of arterial aneurysms. The method is based on an \"induced\" bioelectrical phenomenon that develops in the circulating blood after the vessel in question is placed in a constant magnetic field, the field lines of which are perpendicular to the blood flow direction. Animal and in vitro experiments with induced thrombosis of 100 experimental aneurysms are described. For extrapolating the experiments into clinical conditions a special magnetic device was created that is provided with appliances for external stereotaxis and angiographic control. Nine clinical observations with induced thrombosis of aneurysms were conducted, the follow-up reaching 2 years.", "contents": "[Treatment of aneurysms of the cerebral arteries using stereotaxically oriented external uniform magnetic fields]. The paper presents a theoretical substantiation of the magnet-haemodynamic method of induced thrombosis of arterial aneurysms. The method is based on an \"induced\" bioelectrical phenomenon that develops in the circulating blood after the vessel in question is placed in a constant magnetic field, the field lines of which are perpendicular to the blood flow direction. Animal and in vitro experiments with induced thrombosis of 100 experimental aneurysms are described. For extrapolating the experiments into clinical conditions a special magnetic device was created that is provided with appliances for external stereotaxis and angiographic control. Nine clinical observations with induced thrombosis of aneurysms were conducted, the follow-up reaching 2 years."} {"id": "PMID:1258444", "title": "[Age and changes in the mechanical properties of the cerebral arteries (experimental findings)].", "content": "Experimental investigations into mechanical properties of cerebral arterial vessels of different localization and changes in these properties with age were effected. An analysis of the data obtained showed that the anatomic localization, the biochemical composition and age-specific changes affect the mechanical properties of the walls in these vessels. The available information is of importance in solving some tissues concerned with the pathogenesis of the cerebral circulation disorders and in vasal neurosurgery.", "contents": "[Age and changes in the mechanical properties of the cerebral arteries (experimental findings)]. Experimental investigations into mechanical properties of cerebral arterial vessels of different localization and changes in these properties with age were effected. An analysis of the data obtained showed that the anatomic localization, the biochemical composition and age-specific changes affect the mechanical properties of the walls in these vessels. The available information is of importance in solving some tissues concerned with the pathogenesis of the cerebral circulation disorders and in vasal neurosurgery."} {"id": "PMID:1258445", "title": "[Several parameters of the kinetics of cellular proliferation in human macroglial tumors].", "content": "The thymidine labelling index was studied by autoradiography in 95 human macroglial tumours. In 75 supratentorial tumours the values of the labelling index ranged from 0.05% to 20.10%, while in 20 cerebellar tumours it comprised 0.05% to 1.49%. Macroglial tumours of the large hemispheres could be subdivided with statistical significance into two discrete groups according to their labelling index: the group of slowly growing tumours with the labelling index below 2.5%, and the group of faster growing tumours with the labelling index above 2.5%. Gradual spontaneous malignization of the Group 1 tumours turning into Group 2 tumours is hardly probable. The duration of the DNA synthesis phase in 4 macroglial tumours of the large hemispheres in man varied from 5.7 to 7.5 hours.", "contents": "[Several parameters of the kinetics of cellular proliferation in human macroglial tumors]. The thymidine labelling index was studied by autoradiography in 95 human macroglial tumours. In 75 supratentorial tumours the values of the labelling index ranged from 0.05% to 20.10%, while in 20 cerebellar tumours it comprised 0.05% to 1.49%. Macroglial tumours of the large hemispheres could be subdivided with statistical significance into two discrete groups according to their labelling index: the group of slowly growing tumours with the labelling index below 2.5%, and the group of faster growing tumours with the labelling index above 2.5%. Gradual spontaneous malignization of the Group 1 tumours turning into Group 2 tumours is hardly probable. The duration of the DNA synthesis phase in 4 macroglial tumours of the large hemispheres in man varied from 5.7 to 7.5 hours."} {"id": "PMID:1258449", "title": "[Experience with the use of intravascular interventions using a balloon catheter for several types of cerebral pathology].", "content": "Detachable balloon catheters were used during 38 intravascular procedures in 25 patients with vascular lesions and tumours of the brain. Permanent balloon occlusion of the cavernous part of the internal corotid artery or a reconstruction of this portion of the carotid artery, with its function preserved, was performed in patients with carotid-cavernous fistulas. In arterio-venous aneurysms one or two afferent vessels were occluded, while in cases of arterial aneurysm the latter was blocked itself. In cerebral neoplasms balloon catheters were used to precise the blood supply sources of the tumor, to occlude the vessels supplying meningiomas, and to perform intravital staining of the glial tumors. Positive results were obtained in 24 of the 25 patients. One patient died of middle cerebral artery thrombosis. The method of catheterization and occlusion of cerebral vessels with the aid of balloon catheters proved effective in the examination and treatment of patients with some vascular lesions and tumors of the brain.", "contents": "[Experience with the use of intravascular interventions using a balloon catheter for several types of cerebral pathology]. Detachable balloon catheters were used during 38 intravascular procedures in 25 patients with vascular lesions and tumours of the brain. Permanent balloon occlusion of the cavernous part of the internal corotid artery or a reconstruction of this portion of the carotid artery, with its function preserved, was performed in patients with carotid-cavernous fistulas. In arterio-venous aneurysms one or two afferent vessels were occluded, while in cases of arterial aneurysm the latter was blocked itself. In cerebral neoplasms balloon catheters were used to precise the blood supply sources of the tumor, to occlude the vessels supplying meningiomas, and to perform intravital staining of the glial tumors. Positive results were obtained in 24 of the 25 patients. One patient died of middle cerebral artery thrombosis. The method of catheterization and occlusion of cerebral vessels with the aid of balloon catheters proved effective in the examination and treatment of patients with some vascular lesions and tumors of the brain."} {"id": "PMID:1258450", "title": "[Improved hemagglutination and hemagglutination inhibition tests for arboviruses].", "content": "The capacity of formalinized goose erythrocytes to be agglutinated in interactions with arboviruses was studied. Formalinized goose erythrocytes were found to be as sensitive as native erythrocytes, and were used successfully for diagnosis of arbovirus infections and study of the immune structure of the human population and animals. The superiority of formalinized erythrocytes is determined by the duration of storage (2 years of the observation period) withoug any change in the capacity for agglutination.", "contents": "[Improved hemagglutination and hemagglutination inhibition tests for arboviruses]. The capacity of formalinized goose erythrocytes to be agglutinated in interactions with arboviruses was studied. Formalinized goose erythrocytes were found to be as sensitive as native erythrocytes, and were used successfully for diagnosis of arbovirus infections and study of the immune structure of the human population and animals. The superiority of formalinized erythrocytes is determined by the duration of storage (2 years of the observation period) withoug any change in the capacity for agglutination."} {"id": "PMID:1258451", "title": "[Development of a method for preparing adeno-associated virus type 4 antigen].", "content": "A method for preparation of adeno-associated type 4 virus (AAV-4) purified from group-specific adenovirus antigen by adsorption on formalinized sheep erythrocytes and elution into hypertonic NaCl solution was developed. In 1 M naCl solution the purified AAV-4 retained its infectivity and the complement-fixing and hemagglutinating activities. Separation of AAV-4 and adenovirus group-specific complement-fixing antigen was based on differences in conditions of their adsorption and elution. AAV-4 was inactivated by treatment with both formalin and hydrogen peroxide but retained its complement-fixing antigen and hemagglutinating properties. The purified antigen or virus is recommended for serologic tests and other purposes.", "contents": "[Development of a method for preparing adeno-associated virus type 4 antigen]. A method for preparation of adeno-associated type 4 virus (AAV-4) purified from group-specific adenovirus antigen by adsorption on formalinized sheep erythrocytes and elution into hypertonic NaCl solution was developed. In 1 M naCl solution the purified AAV-4 retained its infectivity and the complement-fixing and hemagglutinating activities. Separation of AAV-4 and adenovirus group-specific complement-fixing antigen was based on differences in conditions of their adsorption and elution. AAV-4 was inactivated by treatment with both formalin and hydrogen peroxide but retained its complement-fixing antigen and hemagglutinating properties. The purified antigen or virus is recommended for serologic tests and other purposes."} {"id": "PMID:1258452", "title": "[Preparation of monospecific sera against oncornaviruses and oncornavirus-associated antigens of human cultured cells].", "content": "A method for preparation of monospecific sera against oncornaviruses and oncornavirus-associated antigens of continouus human cells has been developed on the basis of the results of comparative studies of the properties of viral and virus-associated antigens of the cell. Utilization of an adsorbent from cells free of virus antigen for adsorption of immune sera against oncornaviruses with polyspecific properties resulted in preparation of specific antiviral serum free of antibody to virus-associated antigen of the cell. Sera against virus-associated antigens of the cell containing no antibody to virus were prepared by adsorption with concentrated purified virus isolated from the cell culture.", "contents": "[Preparation of monospecific sera against oncornaviruses and oncornavirus-associated antigens of human cultured cells]. A method for preparation of monospecific sera against oncornaviruses and oncornavirus-associated antigens of continouus human cells has been developed on the basis of the results of comparative studies of the properties of viral and virus-associated antigens of the cell. Utilization of an adsorbent from cells free of virus antigen for adsorption of immune sera against oncornaviruses with polyspecific properties resulted in preparation of specific antiviral serum free of antibody to virus-associated antigen of the cell. Sera against virus-associated antigens of the cell containing no antibody to virus were prepared by adsorption with concentrated purified virus isolated from the cell culture."} {"id": "PMID:1258446", "title": "[Cerebral complications of cervical angiography (frequency, clinical manifestations, preventive measures and treatment)].", "content": "The authors carried out angiographic examinations in 327 patients with tumours in the cervical region and 11 of these (3.36%) demonstrated complications, toxico-allergic ones in 10 and thromboembolism of the cerebral vessels--in one case. Toxico-allergic reactions and dynamic disturbances of the cerebral circulation developed more often in contrasting 2 or more brachycephalic vessels, with a two-fold introduction of the contrast medium into one and the same vascular basin and also in cases of a quick injection of a relatively large amount of the compound into the vertebral artery. Thromboembolism of the cerebral vessels was, apparently, caused by a small clot of blood which occluded an atherosclerotically altered internal carotid artery at the site of its bifurcation. Clinical manifestations of the said complications and a number of preventive and curative measures in case of cerebral complications arising during cervical angiography are considered in detail.", "contents": "[Cerebral complications of cervical angiography (frequency, clinical manifestations, preventive measures and treatment)]. The authors carried out angiographic examinations in 327 patients with tumours in the cervical region and 11 of these (3.36%) demonstrated complications, toxico-allergic ones in 10 and thromboembolism of the cerebral vessels--in one case. Toxico-allergic reactions and dynamic disturbances of the cerebral circulation developed more often in contrasting 2 or more brachycephalic vessels, with a two-fold introduction of the contrast medium into one and the same vascular basin and also in cases of a quick injection of a relatively large amount of the compound into the vertebral artery. Thromboembolism of the cerebral vessels was, apparently, caused by a small clot of blood which occluded an atherosclerotically altered internal carotid artery at the site of its bifurcation. Clinical manifestations of the said complications and a number of preventive and curative measures in case of cerebral complications arising during cervical angiography are considered in detail."} {"id": "PMID:1258456", "title": "[Sedimentation properties of virion RNA of Newcastle disease virus after annealing under different conditions].", "content": "After annealing at high temperatures 50S RNA of Newcastle disease virus was partially degraded. The resulting fragments had the sedimentation coefficient of 23--32S. Solution of dimethylsulfoxide and formamide were used to decrease the temperature of annealing. However, annealing with denaturating agents caused agglomeration of 50S RNA molecules. This phenomenon is discussed.", "contents": "[Sedimentation properties of virion RNA of Newcastle disease virus after annealing under different conditions]. After annealing at high temperatures 50S RNA of Newcastle disease virus was partially degraded. The resulting fragments had the sedimentation coefficient of 23--32S. Solution of dimethylsulfoxide and formamide were used to decrease the temperature of annealing. However, annealing with denaturating agents caused agglomeration of 50S RNA molecules. This phenomenon is discussed."} {"id": "PMID:1258458", "title": "[Analysis of the long-term results of contact of human cell cultures with influenza virus].", "content": "Influenza A/Hong Kong/1/68 and A/Victoria/35/72 viruses may produce in primarily trypsinized human embryo kidney (HEK) cell culture a chronic form of persistence accompanied by periodic emergence of cytopathic changes arrested by additional medium change. This persistence causes morphological changes in HEK culture manifested in the substitution of epithelial elements by fibroblasts and prolongs the \"life\" of culture by over 100 days as compared to the controls. The chronic form of persistence of these viruses in human embryo lung diploid cell culture (HELDC) was accompanied by a cytoproliferogenic effect but did not lead to histomorphological changes and did not exert \"oncogenic-lide\" changes in cell membranes. Inapparent infection with A/Hong Kong/1/68 virus in HELDC did not cause any histomorphological and cytokaryological abnormalities and was accompanied by complete elimination of the virus from the culture. No oncornavirus contamination was found in HELDC cluture either in intact state or after inoculation with influenza virus.", "contents": "[Analysis of the long-term results of contact of human cell cultures with influenza virus]. Influenza A/Hong Kong/1/68 and A/Victoria/35/72 viruses may produce in primarily trypsinized human embryo kidney (HEK) cell culture a chronic form of persistence accompanied by periodic emergence of cytopathic changes arrested by additional medium change. This persistence causes morphological changes in HEK culture manifested in the substitution of epithelial elements by fibroblasts and prolongs the \"life\" of culture by over 100 days as compared to the controls. The chronic form of persistence of these viruses in human embryo lung diploid cell culture (HELDC) was accompanied by a cytoproliferogenic effect but did not lead to histomorphological changes and did not exert \"oncogenic-lide\" changes in cell membranes. Inapparent infection with A/Hong Kong/1/68 virus in HELDC did not cause any histomorphological and cytokaryological abnormalities and was accompanied by complete elimination of the virus from the culture. No oncornavirus contamination was found in HELDC cluture either in intact state or after inoculation with influenza virus."} {"id": "PMID:1258459", "title": "[Serological study of the specificity of leukocyte hepatitis virus].", "content": "For investigation of the specificity of leukocyte hepatitis virus (LHV) in Botkin's disease, 369 patients with virus hepatitis, 96 donors and 61 patients with acute respiratory diseases were examined. The occurrence of specific antibody to LHV was determined by a micromodification of the conventional CFT. LHV was passaged in leukocyte culture stimulated with phytohemagglutinin. A control antigen was a leukocyte culture from the same donor not infected with LHV. An additional control was Epstein-Barr virus passaged in continuous leukocyte suspension cultures. The complement-fixing antibody to LHV was detected in sera from children and adults with virus hepatitis. The number of sera with antibody to LHV was significantly higher than that in the control groups. A rise of antibody titers in the course of the disease in the experimental groups in contrast to the controls attested to certain specificity of LHV in Botkin's disease. No antigenic relationship between LHV and HB antigen was found in serologic tests. The lack of differences in detection of the complement-fixing antibody to Epstein-Barr virus in the experimental and control groups suggests no role of this virus in the etiopathogenesis of Botkin's virus hepatitis.", "contents": "[Serological study of the specificity of leukocyte hepatitis virus]. For investigation of the specificity of leukocyte hepatitis virus (LHV) in Botkin's disease, 369 patients with virus hepatitis, 96 donors and 61 patients with acute respiratory diseases were examined. The occurrence of specific antibody to LHV was determined by a micromodification of the conventional CFT. LHV was passaged in leukocyte culture stimulated with phytohemagglutinin. A control antigen was a leukocyte culture from the same donor not infected with LHV. An additional control was Epstein-Barr virus passaged in continuous leukocyte suspension cultures. The complement-fixing antibody to LHV was detected in sera from children and adults with virus hepatitis. The number of sera with antibody to LHV was significantly higher than that in the control groups. A rise of antibody titers in the course of the disease in the experimental groups in contrast to the controls attested to certain specificity of LHV in Botkin's disease. No antigenic relationship between LHV and HB antigen was found in serologic tests. The lack of differences in detection of the complement-fixing antibody to Epstein-Barr virus in the experimental and control groups suggests no role of this virus in the etiopathogenesis of Botkin's virus hepatitis."} {"id": "PMID:1258453", "title": "[Properties of an infectious agent isolated from the blood of patients with type B hepatitis and donor-antigencarriers].", "content": "An infectious agent different from HB-Ag was detected in sera from patients with hepatitis B and donors-carriers of HB-Ag. This agent can be passaged for a long time in the human tissue-chick embryo system and has a density of 1.38--1.40 g/ml in cesium chloride gradient.", "contents": "[Properties of an infectious agent isolated from the blood of patients with type B hepatitis and donor-antigencarriers]. An infectious agent different from HB-Ag was detected in sera from patients with hepatitis B and donors-carriers of HB-Ag. This agent can be passaged for a long time in the human tissue-chick embryo system and has a density of 1.38--1.40 g/ml in cesium chloride gradient."} {"id": "PMID:1258466", "title": "Barbiturate intoxication. Morbidity and mortality.", "content": "The complications encountered in caring for 185 patients intoxicated with barbiturates were reviewed. The population consisted of 142 patients with long-acting barbiturate concentrations of 8 mg per 100 ml or greater, 20 patients with short-acting barbiturate concentrations of 3 mg per 100 ml or greater and 23 consecutive patients with short-acting barbiturate intoxication referred for monitoring. Pneumonia was the major cause of morbidity and mortality and correlated best with the initial depth of coma and the use of an endotracheal tube in treatment. Cardiovascular instability manifested by pulmonary edema was the next leading cause of morbidity and mortality and correlated best with the initial depth of coma and the quantity of intravenous fluid administered. In retrospect, use of eliminative measures such as dialysis would probably not have altered the outcome in most of the patients who died and attempts at forced diuresis may have contributed to several deaths. Particular emphasis should be placed on the problems of sepsis and fluid therapy in the management of these patients.", "contents": "Barbiturate intoxication. Morbidity and mortality. The complications encountered in caring for 185 patients intoxicated with barbiturates were reviewed. The population consisted of 142 patients with long-acting barbiturate concentrations of 8 mg per 100 ml or greater, 20 patients with short-acting barbiturate concentrations of 3 mg per 100 ml or greater and 23 consecutive patients with short-acting barbiturate intoxication referred for monitoring. Pneumonia was the major cause of morbidity and mortality and correlated best with the initial depth of coma and the use of an endotracheal tube in treatment. Cardiovascular instability manifested by pulmonary edema was the next leading cause of morbidity and mortality and correlated best with the initial depth of coma and the quantity of intravenous fluid administered. In retrospect, use of eliminative measures such as dialysis would probably not have altered the outcome in most of the patients who died and attempts at forced diuresis may have contributed to several deaths. Particular emphasis should be placed on the problems of sepsis and fluid therapy in the management of these patients."} {"id": "PMID:1258467", "title": "An evaluation of bilateral breast carcinoma. Simultaneous and sequential lesions.", "content": "The detection of bilateral breast carcinoma, simultaneous or nonsimultaneous, appears to be increasing. Undoubtedly a major factor in this is the increased use of mammography and xeromammography. In a 21-year period at Saint John's Hospital and Health Center, 1,189 cases of primary breast carcinoma were treated, of which 34 (2.9 percent) were bilateral. However, from 1972 to 1974 the incidence has risen from 1.9 to 10.8 percent, with a simultaneous rise in numbers of xeromammograms made. Xeromammography should be done routinely in patients in whom carcinoma of the breast is suspected. Its use should also be an integral part of the follow-up in patients in whom mastectomy has been carried out previously.", "contents": "An evaluation of bilateral breast carcinoma. Simultaneous and sequential lesions. The detection of bilateral breast carcinoma, simultaneous or nonsimultaneous, appears to be increasing. Undoubtedly a major factor in this is the increased use of mammography and xeromammography. In a 21-year period at Saint John's Hospital and Health Center, 1,189 cases of primary breast carcinoma were treated, of which 34 (2.9 percent) were bilateral. However, from 1972 to 1974 the incidence has risen from 1.9 to 10.8 percent, with a simultaneous rise in numbers of xeromammograms made. Xeromammography should be done routinely in patients in whom carcinoma of the breast is suspected. Its use should also be an integral part of the follow-up in patients in whom mastectomy has been carried out previously."} {"id": "PMID:1258455", "title": "[Activity of DNA-dependent RNA polymerases A and B in spleen nuclei of mice infected with Rauscher leukemia virus].", "content": "The activity of DNA-dependent RNA polymerase A and B in isolated nuclei of spleens of mice infected with Rauscher leukemia virus was studied. A 3-fold increase in the activity of both RNA-polymerases in leukemic spleens was established. Study of the properties of RNA-polymerase B from nuclei of spleens of mice infected with Rauscher virus in comparison with the enzyme from normal tissue revealed the existence of some specific features in the enzyme from leukemic cells. The nature of the increased activity of RNA-polymerase B in leukemic cells is discussed.", "contents": "[Activity of DNA-dependent RNA polymerases A and B in spleen nuclei of mice infected with Rauscher leukemia virus]. The activity of DNA-dependent RNA polymerase A and B in isolated nuclei of spleens of mice infected with Rauscher leukemia virus was studied. A 3-fold increase in the activity of both RNA-polymerases in leukemic spleens was established. Study of the properties of RNA-polymerase B from nuclei of spleens of mice infected with Rauscher virus in comparison with the enzyme from normal tissue revealed the existence of some specific features in the enzyme from leukemic cells. The nature of the increased activity of RNA-polymerase B in leukemic cells is discussed."} {"id": "PMID:1258468", "title": "Microsurgical treatment of hermifacial spasm.", "content": "Five cases of idiopathic hemifacial spasm have been successfully treated by operative manipulation of arterial branches compressing the VIIth nerve in the posterior fossa. Terminology, clinical presentation, pathology and therapeutic approaches to hemifacial spasm are discussed. Hearing loss due to operatively induced vascular impairment of the inner ear, a complication in our first case, should be avoidable. Our experience indicates that hemifacial spasm reflects mild chronic compression of the facial nerve. The proposed mechanism is transaxonal excitation between afferent and efferent fibers.", "contents": "Microsurgical treatment of hermifacial spasm. Five cases of idiopathic hemifacial spasm have been successfully treated by operative manipulation of arterial branches compressing the VIIth nerve in the posterior fossa. Terminology, clinical presentation, pathology and therapeutic approaches to hemifacial spasm are discussed. Hearing loss due to operatively induced vascular impairment of the inner ear, a complication in our first case, should be avoidable. Our experience indicates that hemifacial spasm reflects mild chronic compression of the facial nerve. The proposed mechanism is transaxonal excitation between afferent and efferent fibers."} {"id": "PMID:1258457", "title": "[Role of phagocytes and antibodies in freeing the body from influenza virus].", "content": "Persistence of influenza virus in normal and immune mice was studied by determinations of the virus infectivity and by the immunofluorescence procedures. After intraperitoneal inoculation the virus could be found in macrophages of the peritoneal exudate in both normal and immune animals. However, in macrophages of normal mice synthesis of V- and S-antigens of influenza virus occurred indicating the possibility of virus reproduction in them, whereas in macrophages of immune animals there was practically no synthesis of S-antigen despite a greater number of cells with V-antigen of influenza virus in their cytoplasma. The assumption that elimination of influenza virus from the body is due to specific antibody and immunologically changed macrophage elements is substantiated.", "contents": "[Role of phagocytes and antibodies in freeing the body from influenza virus]. Persistence of influenza virus in normal and immune mice was studied by determinations of the virus infectivity and by the immunofluorescence procedures. After intraperitoneal inoculation the virus could be found in macrophages of the peritoneal exudate in both normal and immune animals. However, in macrophages of normal mice synthesis of V- and S-antigens of influenza virus occurred indicating the possibility of virus reproduction in them, whereas in macrophages of immune animals there was practically no synthesis of S-antigen despite a greater number of cells with V-antigen of influenza virus in their cytoplasma. The assumption that elimination of influenza virus from the body is due to specific antibody and immunologically changed macrophage elements is substantiated."} {"id": "PMID:1258485", "title": "[Diabetes mellitus: puberty and angiopathy (author's transl)].", "content": "It is inferred from a study of 140 cases of diabetes mellitus commencing between the ages of 10 and 17 that puberty causes the premative and accelorated appearance of angiopathy. The characteristic course of the angiopathy is not affected by puberty and does not necessarily persue an absolutely malignant form. It is genetically pre-determined and undergoes only insignificant enviornmental modifications subsequently.", "contents": "[Diabetes mellitus: puberty and angiopathy (author's transl)]. It is inferred from a study of 140 cases of diabetes mellitus commencing between the ages of 10 and 17 that puberty causes the premative and accelorated appearance of angiopathy. The characteristic course of the angiopathy is not affected by puberty and does not necessarily persue an absolutely malignant form. It is genetically pre-determined and undergoes only insignificant enviornmental modifications subsequently."} {"id": "PMID:1258486", "title": "[Insulin and adipose tissue (author's transl)].", "content": "The effect of insulin and glucose on lipolysis, on the re-esterification rate of free fatty acids and on glucose oxidation was investigated in isolated fat cells of the greater omentum. Insulin alone inhibited increased lipolysis only, but had no effect on normal basal lipolysis. The insulin effect on lipolysis was not altered by glucose. The re-esterification rate of free fatty acids was stimulated by glucose in a dose-dependent way. Insulin had no effect on the re-esterification rate of free fatty acids in the presence or absence of glucose. Basal glucose oxidation was slightly, but significantly increased by insulin. It is concluded that the prinicipal action of insulin in human adipose tissue is the inhibition of increased lipolysis, whereas glucose metabolism remains largely unaffected by insulin.", "contents": "[Insulin and adipose tissue (author's transl)]. The effect of insulin and glucose on lipolysis, on the re-esterification rate of free fatty acids and on glucose oxidation was investigated in isolated fat cells of the greater omentum. Insulin alone inhibited increased lipolysis only, but had no effect on normal basal lipolysis. The insulin effect on lipolysis was not altered by glucose. The re-esterification rate of free fatty acids was stimulated by glucose in a dose-dependent way. Insulin had no effect on the re-esterification rate of free fatty acids in the presence or absence of glucose. Basal glucose oxidation was slightly, but significantly increased by insulin. It is concluded that the prinicipal action of insulin in human adipose tissue is the inhibition of increased lipolysis, whereas glucose metabolism remains largely unaffected by insulin."} {"id": "PMID:1258487", "title": "[The effect of Glipizide on the blood glucose and insulin in non-ketotic diabetes mellitus (author's transl)].", "content": "9 patients suffering from non-ketotic diabetes were treated for 7 days with glipizide, a sulphonylurea derivative. A decrease in blood glucose level was observed in 6 patients during the course of the day, accompanied by an increase in immunoreactive insulin during the first half of the day and an increase in the insulinogenic index. In one patient with insulinopenic diabetes glipizide had only a very small effect on the blood glucose and insulin concentration. 2 patients suffering from insulin resistance caused by type IV hyperlipoproteinanemia and obesity showed an increase in insulin, but no decrease in blood glucose concentration. These results are a further indication that sulphonylurea agents should be administered only in the case of certain specific types of diabetes, because no therapeutic response can be expected in diabetes caused by insulinopenia and insulin resistance.", "contents": "[The effect of Glipizide on the blood glucose and insulin in non-ketotic diabetes mellitus (author's transl)]. 9 patients suffering from non-ketotic diabetes were treated for 7 days with glipizide, a sulphonylurea derivative. A decrease in blood glucose level was observed in 6 patients during the course of the day, accompanied by an increase in immunoreactive insulin during the first half of the day and an increase in the insulinogenic index. In one patient with insulinopenic diabetes glipizide had only a very small effect on the blood glucose and insulin concentration. 2 patients suffering from insulin resistance caused by type IV hyperlipoproteinanemia and obesity showed an increase in insulin, but no decrease in blood glucose concentration. These results are a further indication that sulphonylurea agents should be administered only in the case of certain specific types of diabetes, because no therapeutic response can be expected in diabetes caused by insulinopenia and insulin resistance."} {"id": "PMID:1258488", "title": "[Is there a feed-back mechanism between serum gastrin concentration and gastrin release (author's transl)].", "content": "The dialysability of gastrin heptadecapeptide was investigated in a model arrangement. The amounts of gastrin passing through the dialysis membrane during a 6-hour dialysis procedure are very small. Furthermore, the serum gastrin concentrations were measured during a 6-hour haemodialysis session with and without simultaneous pentagastrin infusion (0.003 mug/kg/h) in 8 patients on intermittent haemodialysis. There is a continuous decrease in the serum gastrin concentration during the 6-hour dialysis period with simultaneous pentagastrin infusion, while in the investigation without pentagastrin infusion phases of increase in serum gastrin levels are observed. In view of this different response of the serum gastrin curve it is suggested that a direct feed-back mechanism exists between the serum gastrin concentration and gastrin release, a mechanism which was interrupted by the pentagastrin infusion in the present investigation.", "contents": "[Is there a feed-back mechanism between serum gastrin concentration and gastrin release (author's transl)]. The dialysability of gastrin heptadecapeptide was investigated in a model arrangement. The amounts of gastrin passing through the dialysis membrane during a 6-hour dialysis procedure are very small. Furthermore, the serum gastrin concentrations were measured during a 6-hour haemodialysis session with and without simultaneous pentagastrin infusion (0.003 mug/kg/h) in 8 patients on intermittent haemodialysis. There is a continuous decrease in the serum gastrin concentration during the 6-hour dialysis period with simultaneous pentagastrin infusion, while in the investigation without pentagastrin infusion phases of increase in serum gastrin levels are observed. In view of this different response of the serum gastrin curve it is suggested that a direct feed-back mechanism exists between the serum gastrin concentration and gastrin release, a mechanism which was interrupted by the pentagastrin infusion in the present investigation."} {"id": "PMID:1258489", "title": "[The effect of oxyphenbutazone and flufenamic acid in vitro on the purine salvage pathway of human lymphocytes (author's transl)].", "content": "The effect of oxyphenbutazone and flufenamic acid was investigated on the enzymes of the purine salvage pathway of human lymphocytes in vitro. A distinct decrease in adenine-phosphoribosyltransferase activity and in guanine-hypoxanthine-phosphoribosyltransferase activity was observed following the administration of either pharmacological preparation. The loss of enzyme activity was 23 to 39%. The pharmaceuticals were used at a concentration of 50 mug%.", "contents": "[The effect of oxyphenbutazone and flufenamic acid in vitro on the purine salvage pathway of human lymphocytes (author's transl)]. The effect of oxyphenbutazone and flufenamic acid was investigated on the enzymes of the purine salvage pathway of human lymphocytes in vitro. A distinct decrease in adenine-phosphoribosyltransferase activity and in guanine-hypoxanthine-phosphoribosyltransferase activity was observed following the administration of either pharmacological preparation. The loss of enzyme activity was 23 to 39%. The pharmaceuticals were used at a concentration of 50 mug%."} {"id": "PMID:1258490", "title": "[Clinical results with dopamine in acute renal failure (author's transl)].", "content": "Dopamine possesses specific pharmacological actions which distinguish it from the other catecholamines. Apart from its positive inotropic effect, dopamine exerts a favourable influence on renal function with an increase in renal blood flow and alterations in intrarenal haemodynamics. The use of dopamine in the early stages of acute oliguric failure is recommended on the basis of the good therapeutic response achieved in a series of cases.", "contents": "[Clinical results with dopamine in acute renal failure (author's transl)]. Dopamine possesses specific pharmacological actions which distinguish it from the other catecholamines. Apart from its positive inotropic effect, dopamine exerts a favourable influence on renal function with an increase in renal blood flow and alterations in intrarenal haemodynamics. The use of dopamine in the early stages of acute oliguric failure is recommended on the basis of the good therapeutic response achieved in a series of cases."} {"id": "PMID:1258505", "title": "[Transfemoral coronary angiography. I. Report on the decreasing complication rate in the increasing number of cases].", "content": "4950 coronary arteriographies performed by the percutaneous transfemoral technique (Judkins) are reviewed with respect to mortality, morbidity of myocardial infarctions and cerebral emboli, incidence of femoral thrombectomies and incidence of threatening events like arrhythmias and contrast reactions. With increasing number of coronary arteriographies that were performed yearly the incidence of all complications could be reduced by more than 90%.", "contents": "[Transfemoral coronary angiography. I. Report on the decreasing complication rate in the increasing number of cases]. 4950 coronary arteriographies performed by the percutaneous transfemoral technique (Judkins) are reviewed with respect to mortality, morbidity of myocardial infarctions and cerebral emboli, incidence of femoral thrombectomies and incidence of threatening events like arrhythmias and contrast reactions. With increasing number of coronary arteriographies that were performed yearly the incidence of all complications could be reduced by more than 90%."} {"id": "PMID:1258506", "title": "[Transfemoral coronary angiography. II. Technical aspects of risk lowering].", "content": "Based on an experience of 4950 coronary arteriographies and a review of the literature common complications of transfemoral coronary arteriography are named, their mechanisms are analyzed and technical modifications of the procedure are suggested that we found useful to decrease the risk associated with this diagnostic test. Since throboembolic complications are a central problem of the transfemoral technique, various mechanisms producing myocardial and cerebral emboli are carefully analyzed. The significance of routine systemic heparinization has been emphasized repeatedly, but the contribution to safety of mechanical catheter tip debridement that can be reliably achieved by a meticulous ritual of appropriate steps is not universally recognized. These steps include a careful guidewire technique, insisting on spontaneous free back-dripping of blood from newly introduced catheters after removal of the guidewire, aspiration of blood with a syringe and flushing with saline and contrast. Careful observation of the blood pressure contour is mandatory whenever the catheter is advanced. In view of the time-thrombogenicity relation of catheter material, the procedure has to be performed expeditiously. After apparent solution of the problem of thromboembolic accidents, the only major complications occurred in patients with severe left main coronary artery lesions. Whenever disease of the left main coronary artery can be anticipated by a suggestive history, by highly abnormal ECG changes with exercise or by calcifications of the coronary arteries, the number of contrast injections should be reduced to a minimum necessary to adequately demonstrate the severity of the stenosis and the anatomy of the peripheral vessels for possible bypass surgery.", "contents": "[Transfemoral coronary angiography. II. Technical aspects of risk lowering]. Based on an experience of 4950 coronary arteriographies and a review of the literature common complications of transfemoral coronary arteriography are named, their mechanisms are analyzed and technical modifications of the procedure are suggested that we found useful to decrease the risk associated with this diagnostic test. Since throboembolic complications are a central problem of the transfemoral technique, various mechanisms producing myocardial and cerebral emboli are carefully analyzed. The significance of routine systemic heparinization has been emphasized repeatedly, but the contribution to safety of mechanical catheter tip debridement that can be reliably achieved by a meticulous ritual of appropriate steps is not universally recognized. These steps include a careful guidewire technique, insisting on spontaneous free back-dripping of blood from newly introduced catheters after removal of the guidewire, aspiration of blood with a syringe and flushing with saline and contrast. Careful observation of the blood pressure contour is mandatory whenever the catheter is advanced. In view of the time-thrombogenicity relation of catheter material, the procedure has to be performed expeditiously. After apparent solution of the problem of thromboembolic accidents, the only major complications occurred in patients with severe left main coronary artery lesions. Whenever disease of the left main coronary artery can be anticipated by a suggestive history, by highly abnormal ECG changes with exercise or by calcifications of the coronary arteries, the number of contrast injections should be reduced to a minimum necessary to adequately demonstrate the severity of the stenosis and the anatomy of the peripheral vessels for possible bypass surgery."} {"id": "PMID:1258507", "title": "[Heart function in patients with and without wall dyskinesia. Echocardiographic-cineangiographic comparative study].", "content": "The mean velocity of circumferential fibre shortening determined by echo and angiography is a good parameter for the assessment of the basal left ventricular contractility. It remains relatively constant in acute and chronic changes in preload i.e. compensated volume overload, though the inverse relation to afterload is still maintained. For the calculation of mean VCF we assumed the heart to be a rotational ellipsoid. Models and extrapolation of curve are not necessary for the calculation of this parameter. On the basis of these considerations we investigated with the echographic and angiographic technique 5 patient groups having normal cardiac function (group I, IV) and abnormal function (group II, III and V).", "contents": "[Heart function in patients with and without wall dyskinesia. Echocardiographic-cineangiographic comparative study]. The mean velocity of circumferential fibre shortening determined by echo and angiography is a good parameter for the assessment of the basal left ventricular contractility. It remains relatively constant in acute and chronic changes in preload i.e. compensated volume overload, though the inverse relation to afterload is still maintained. For the calculation of mean VCF we assumed the heart to be a rotational ellipsoid. Models and extrapolation of curve are not necessary for the calculation of this parameter. On the basis of these considerations we investigated with the echographic and angiographic technique 5 patient groups having normal cardiac function (group I, IV) and abnormal function (group II, III and V)."} {"id": "PMID:1258508", "title": "[Arrhythmia analysis--arrhythmia control (comparative studies of 4 small computers for automatic electrocardiography control)].", "content": "Four arrhythmia computers presently available on the market were tested with respect to their efficiency in identifying abnormal QRS-complexes. A considerable variation for the calculated sensitivity and specificity has been found with a highest value for sensitivity (92.9%) combined with a low specificity (72.4%), and a highest value for specificity (100%) combined with a very low sensitivity (36.6%). The best results were obtained by a computer with a sensitivity of 90.9% and a specificity of 98.5%. For the routine use of these computers in the CCU common artifacts (e.g. muscle potentials) must influence their performance in a practical way: neither should minor artifacts stop the function completely nor should the computer continue to measure with a high level of \"noise\". Based upon the results of these test series suggestions for the concept of arrhythmia computers for CCU are presented.", "contents": "[Arrhythmia analysis--arrhythmia control (comparative studies of 4 small computers for automatic electrocardiography control)]. Four arrhythmia computers presently available on the market were tested with respect to their efficiency in identifying abnormal QRS-complexes. A considerable variation for the calculated sensitivity and specificity has been found with a highest value for sensitivity (92.9%) combined with a low specificity (72.4%), and a highest value for specificity (100%) combined with a very low sensitivity (36.6%). The best results were obtained by a computer with a sensitivity of 90.9% and a specificity of 98.5%. For the routine use of these computers in the CCU common artifacts (e.g. muscle potentials) must influence their performance in a practical way: neither should minor artifacts stop the function completely nor should the computer continue to measure with a high level of \"noise\". Based upon the results of these test series suggestions for the concept of arrhythmia computers for CCU are presented."} {"id": "PMID:1258509", "title": "[Cardiofacial syndrome].", "content": "A case of cardiofacial syndrome is reported, consisting in congenital heart disease combined with unilateral lower facial paresis. The whole cases of the literature and the pathogenetic mechanisms are discussed.", "contents": "[Cardiofacial syndrome]. A case of cardiofacial syndrome is reported, consisting in congenital heart disease combined with unilateral lower facial paresis. The whole cases of the literature and the pathogenetic mechanisms are discussed."} {"id": "PMID:1258510", "title": "[Transumbilical heart diagnosis and ballon atrioseptostomy].", "content": "The way of catheter insertion through the umbilical vein is presented. We attempted the transumbilical heart catheterization in 63 patients, in 14 we failed to make an exact diagnosis. Furthermore, in 17 out of 26 patients we could perform the balloon atrial septostomy transumbilically. The possible complications are discussed and this access is recommended as an elegant and time-saving method.", "contents": "[Transumbilical heart diagnosis and ballon atrioseptostomy]. The way of catheter insertion through the umbilical vein is presented. We attempted the transumbilical heart catheterization in 63 patients, in 14 we failed to make an exact diagnosis. Furthermore, in 17 out of 26 patients we could perform the balloon atrial septostomy transumbilically. The possible complications are discussed and this access is recommended as an elegant and time-saving method."} {"id": "PMID:1258511", "title": "[Postoperative endocardial fibrosis following mitral valve prosthesis].", "content": "Uncommon observation of endocardial fibroelastosis of the left auricle and ventricle found at autopsy. The 46-year-old female patient had her mitral valve replaced 15 months ago because of mitral stenosis (and slight incompetence). The left auricle with certainty did not show endocardial fibrosis at the time of operation. The therefore acquired postoperative fibroelastosis of the left auricle is probably caused mechanically resp. by hypoxia since postoperatively valvular incompetence and restenosis with severe thrombosis of the artificial valve developed. There are no reasons to assume an inflammatory etiology. It must remain open if the fibroelastosis of the left ventricle was congenital. Its possible etiology - if it was also acquired - is discussed.", "contents": "[Postoperative endocardial fibrosis following mitral valve prosthesis]. Uncommon observation of endocardial fibroelastosis of the left auricle and ventricle found at autopsy. The 46-year-old female patient had her mitral valve replaced 15 months ago because of mitral stenosis (and slight incompetence). The left auricle with certainty did not show endocardial fibrosis at the time of operation. The therefore acquired postoperative fibroelastosis of the left auricle is probably caused mechanically resp. by hypoxia since postoperatively valvular incompetence and restenosis with severe thrombosis of the artificial valve developed. There are no reasons to assume an inflammatory etiology. It must remain open if the fibroelastosis of the left ventricle was congenital. Its possible etiology - if it was also acquired - is discussed."} {"id": "PMID:1258512", "title": "[Familial preductal aortic coarctation. Report on a sibling observation].", "content": "The cases of two siblings, who died of preductal coarctation of the aorta, are reported. The rare familiar congenital cardiopathies are of special importance for the etiological questions and for judgement of the prognosis of inheritance.", "contents": "[Familial preductal aortic coarctation. Report on a sibling observation]. The cases of two siblings, who died of preductal coarctation of the aorta, are reported. The rare familiar congenital cardiopathies are of special importance for the etiological questions and for judgement of the prognosis of inheritance."} {"id": "PMID:1258513", "title": "[Left ventricular function in mitral valve stenosis].", "content": "In 12 patients with mitral stenosis left ventricular performance was assessed by pharmacologically (Methoxamine) induced increased afterload. At rest ventricular enddiastolic pressure (6.2 +/- 3.1 mm Hg), left ventricular enddiastolic volume (68 +/- 20 ml/m2), endsystolic volume (26 +/- 11 ml/m2) and left ventricular ejection fraction (0.63 +/- 0.06) were normal in each subject. Methoxamine induced a mean increment in peak systolic atrial pressure of 65 mm Hg. Left ventricular stroke volume, stroke work, stroke power, enddiastolic pressure and volume increased with Methoxamine in each patient. The mean left ventricular ejection fraction remained unchanged for the group and remained within the normal range for all patients. No difference was observed between the response of the mitral stenosis group and a control group of 10 normal subjects with the exception of the account of mitral regurgitation during the pressure load in 9 mitral stenosis patients. This study indicates the left ventricle in mitral stenosis is capable of a normal response to a pressure load. No evidence of impaired left ventricular function was detected in this group of patients.", "contents": "[Left ventricular function in mitral valve stenosis]. In 12 patients with mitral stenosis left ventricular performance was assessed by pharmacologically (Methoxamine) induced increased afterload. At rest ventricular enddiastolic pressure (6.2 +/- 3.1 mm Hg), left ventricular enddiastolic volume (68 +/- 20 ml/m2), endsystolic volume (26 +/- 11 ml/m2) and left ventricular ejection fraction (0.63 +/- 0.06) were normal in each subject. Methoxamine induced a mean increment in peak systolic atrial pressure of 65 mm Hg. Left ventricular stroke volume, stroke work, stroke power, enddiastolic pressure and volume increased with Methoxamine in each patient. The mean left ventricular ejection fraction remained unchanged for the group and remained within the normal range for all patients. No difference was observed between the response of the mitral stenosis group and a control group of 10 normal subjects with the exception of the account of mitral regurgitation during the pressure load in 9 mitral stenosis patients. This study indicates the left ventricle in mitral stenosis is capable of a normal response to a pressure load. No evidence of impaired left ventricular function was detected in this group of patients."} {"id": "PMID:1258514", "title": "[Influence of propafenon on hemodynamics of the left ventricle and atrioventricular conduction with special reference to the WPW syndrome].", "content": "15 patients were injected 2 mg/kg Propafenon intravenously in 3 minutes. In 10 patients the changes of the atrio-ventricular conduction and the sinus-node recovery time were measured. In 5 out of these 10 patients the influence on the left ventricular systolic pressure, the left ventricular enddiastolic pressure and the dp/dtmax was also measured. 4 patients had a WPW-syndrom and one patient an AV nodal tachycardia. There was a significant increase of the PQ-time (16,7%), the AH interval (9%), HV interval (33%) and the width of the QRS complex (13.8%). The intratrial conduction (PA-time), the heart rate and the sinus-node recovery time were not influenced. In 6 out of 7 patients the effective refractory period of the AV node was prolonged and in one it remained unchanged. There was a statistically significant decrease of the dp/dt, the heart rate staying the same. The systolic pressure decreased slightly and the enddiastolic pressure increased insignificantly. In 3 out of 4 patients with WPW syndrome the accessory pathway was blocked and in the 4th the effective refractory period of the pathway prolonged. In 3 out of these 4 patients a tachycardia could be initiated by the extra-stimulus method which was not possible after administration of the drug.", "contents": "[Influence of propafenon on hemodynamics of the left ventricle and atrioventricular conduction with special reference to the WPW syndrome]. 15 patients were injected 2 mg/kg Propafenon intravenously in 3 minutes. In 10 patients the changes of the atrio-ventricular conduction and the sinus-node recovery time were measured. In 5 out of these 10 patients the influence on the left ventricular systolic pressure, the left ventricular enddiastolic pressure and the dp/dtmax was also measured. 4 patients had a WPW-syndrom and one patient an AV nodal tachycardia. There was a significant increase of the PQ-time (16,7%), the AH interval (9%), HV interval (33%) and the width of the QRS complex (13.8%). The intratrial conduction (PA-time), the heart rate and the sinus-node recovery time were not influenced. In 6 out of 7 patients the effective refractory period of the AV node was prolonged and in one it remained unchanged. There was a statistically significant decrease of the dp/dt, the heart rate staying the same. The systolic pressure decreased slightly and the enddiastolic pressure increased insignificantly. In 3 out of 4 patients with WPW syndrome the accessory pathway was blocked and in the 4th the effective refractory period of the pathway prolonged. In 3 out of these 4 patients a tachycardia could be initiated by the extra-stimulus method which was not possible after administration of the drug."} {"id": "PMID:1258515", "title": "[Regional myocardial perfusion on distribution through coronary drugs. I. Method of myocardial double radionuclide scintigraphy].", "content": "A methodical introduction of the measurement of regional myocardial microperfusion is given. Based on the results of selective coronary perfusion scintigraphy in this technique two isotopes are injected into the same coronary artery with a characteristic time interval between the two injections. The influence of the coronary active drug on regional myocardial microperfusion can be measured, when the second isotope is injected after a time interval corresponding to the maximum drug effect. The second isotope then marks the actual regional microperfusion under the influence of the drug. The two isotopes can be discriminated by their characteristic energy spectra and then quantitatively be compared. The scans are taken in different positions and then compared with the corresponding coronarograms and left ventriculograms.", "contents": "[Regional myocardial perfusion on distribution through coronary drugs. I. Method of myocardial double radionuclide scintigraphy]. A methodical introduction of the measurement of regional myocardial microperfusion is given. Based on the results of selective coronary perfusion scintigraphy in this technique two isotopes are injected into the same coronary artery with a characteristic time interval between the two injections. The influence of the coronary active drug on regional myocardial microperfusion can be measured, when the second isotope is injected after a time interval corresponding to the maximum drug effect. The second isotope then marks the actual regional microperfusion under the influence of the drug. The two isotopes can be discriminated by their characteristic energy spectra and then quantitatively be compared. The scans are taken in different positions and then compared with the corresponding coronarograms and left ventriculograms."} {"id": "PMID:1258516", "title": "[Regional myocardial perfusion redistribution through coronary drugs. II. Influence of dipyridamole and oxyfedrin on regional perfusion distribution].", "content": "The influence of Dipyridamol and Oxyfedrin on regional myocardial precapillary microperfusion patterns was investigated in groups of 15 and 13 patients by means of selective double lable perfusion scintigraphy. Automatic impulse rate integration allows the comparison of different perfusion areas in the same scintigram as well as the comparison of different identical regions in different scintigrams. The scans were taken in two positions (frontal and l.a.o.). Microperfusion patterns were measured before and after the intravenous application of the drug. We found a typical shift of the microperfusion patterns with both medicaments. Under the influence of Oxyfedrin and Dipyridamol there was an increase of the relative microperfusion intensity in the vicinity of the major arteries but there were great differences as to the degree of their reaction maximum. Besides the results of the groups some typical cases are demonstrated. The method allows a satisfactory measurement of differences in the regional precapillary myocardial perfusion under the influence of coronary active drugs. We believe that statements on physiologic and pathologic functions are possible.", "contents": "[Regional myocardial perfusion redistribution through coronary drugs. II. Influence of dipyridamole and oxyfedrin on regional perfusion distribution]. The influence of Dipyridamol and Oxyfedrin on regional myocardial precapillary microperfusion patterns was investigated in groups of 15 and 13 patients by means of selective double lable perfusion scintigraphy. Automatic impulse rate integration allows the comparison of different perfusion areas in the same scintigram as well as the comparison of different identical regions in different scintigrams. The scans were taken in two positions (frontal and l.a.o.). Microperfusion patterns were measured before and after the intravenous application of the drug. We found a typical shift of the microperfusion patterns with both medicaments. Under the influence of Oxyfedrin and Dipyridamol there was an increase of the relative microperfusion intensity in the vicinity of the major arteries but there were great differences as to the degree of their reaction maximum. Besides the results of the groups some typical cases are demonstrated. The method allows a satisfactory measurement of differences in the regional precapillary myocardial perfusion under the influence of coronary active drugs. We believe that statements on physiologic and pathologic functions are possible."} {"id": "PMID:1258517", "title": "[Alternating and intermittent bilateral bundle-branch block in acute myocardial infarct with development of total atrioventricular block].", "content": "The development of bilateral bundle branch block of various degree in the course of an acute myocardial infarction was demonstrated in a 74-year-old man during continuous ecg-monitoring. Initially there was a tachycardia- and bradycardia-dependent left bundle branch block, followed by a right bundle branch block with second degree type II AV block (Mobitz), and finally complete bilateral bundle branch block with asystole. Different combinations of incomplete block were shown and the presence of type I and type II second degree block within the bundle branches could be demonstrated; Wenckebach periods became indirectly visualized through changes in the AV conduction. This case illustrates the prognostic importance of progressive intraventricular conduction disturbance and reveals the multiplicity and possible mechanisms of conduction defects within the bundle branches.", "contents": "[Alternating and intermittent bilateral bundle-branch block in acute myocardial infarct with development of total atrioventricular block]. The development of bilateral bundle branch block of various degree in the course of an acute myocardial infarction was demonstrated in a 74-year-old man during continuous ecg-monitoring. Initially there was a tachycardia- and bradycardia-dependent left bundle branch block, followed by a right bundle branch block with second degree type II AV block (Mobitz), and finally complete bilateral bundle branch block with asystole. Different combinations of incomplete block were shown and the presence of type I and type II second degree block within the bundle branches could be demonstrated; Wenckebach periods became indirectly visualized through changes in the AV conduction. This case illustrates the prognostic importance of progressive intraventricular conduction disturbance and reveals the multiplicity and possible mechanisms of conduction defects within the bundle branches."} {"id": "PMID:1258518", "title": "[The - wave of apexcardiography in total AV block].", "content": "The apex cardiogram (acg) in three patients with total heart block showed also during closure of the a.v. valves a-waves, which modified the shape of the systolic wave of the acg. This means that in these cases the a-wave is not caused by impingement of the blood inflow from the atrium on the ventricular wall by contraction of the atrium itself.", "contents": "[The - wave of apexcardiography in total AV block]. The apex cardiogram (acg) in three patients with total heart block showed also during closure of the a.v. valves a-waves, which modified the shape of the systolic wave of the acg. This means that in these cases the a-wave is not caused by impingement of the blood inflow from the atrium on the ventricular wall by contraction of the atrium itself."} {"id": "PMID:1258519", "title": "[Serum potassium and urine potassium concentrations following single and repeated potassium load].", "content": "Levels of potassium concentration have been determined after single and repeated oral application of potassium. The maximum level of serumpotassium concentration was found about 2 hours after intake of 120 mval potassium. The concentration of potassium did not return to basic values within 24 hours. The concentration of potassium in urine increased during the first 4 hours. 6 to 12 hours later the maximum level is achieved. This leads to the conclusion that enterally applicated potassium is shifted into the intracellular space and is later released into the extracellular space. Repeated application of potassium in diminished dosages leads to reduced increased of serum and urin potassium concentration. The increase in concentration remains relatively constant during the whole period of application. For longterm therapy with oral potassium an application of a minimum dosage of 40 mval potassium in an 8 to 12 hours rhythm is reasonable.", "contents": "[Serum potassium and urine potassium concentrations following single and repeated potassium load]. Levels of potassium concentration have been determined after single and repeated oral application of potassium. The maximum level of serumpotassium concentration was found about 2 hours after intake of 120 mval potassium. The concentration of potassium did not return to basic values within 24 hours. The concentration of potassium in urine increased during the first 4 hours. 6 to 12 hours later the maximum level is achieved. This leads to the conclusion that enterally applicated potassium is shifted into the intracellular space and is later released into the extracellular space. Repeated application of potassium in diminished dosages leads to reduced increased of serum and urin potassium concentration. The increase in concentration remains relatively constant during the whole period of application. For longterm therapy with oral potassium an application of a minimum dosage of 40 mval potassium in an 8 to 12 hours rhythm is reasonable."} {"id": "PMID:1258521", "title": "[Ergometric determination of cardiac output in 1500 Swiss children and adults of both sexes, aged 5 to 65 years. Relation to body constitution, sex, age and work capacity in the step test (Part 2)].", "content": "The stroke volume of the heart during exercise in upright position (steptest) was determined in 1500 Swiss children and adults of either sex, aged 5 to 65 years. The use of the simplified ergometric method (Strehler) allowed to carry out these determinations mainly in series and without any difficulty. Average absolute values are presented for each year during childhood and adolescence and for each decade in the period of adult life. The stroke volume is lower in the female than in the male group; this refers to absolute values as well as to values relative to body size. The absolute values are approximately proportional to body weight, to the cube of body height and to a standard volume calculated from body height and body weight. There is a typical age-depending course of the relationship between stroke volume and body size (standard volume), the development of the stroke volume showing a minimum before and a maximum during puberty. Provided work load in per cent of the maximal working capacity is the same the stroke volume of the heart during exercise in upright position remains unchanged until the age of about 55 to 60 years. The practical scope of the investigation was to collect data for the setting up of a new stroke volume standard.", "contents": "[Ergometric determination of cardiac output in 1500 Swiss children and adults of both sexes, aged 5 to 65 years. Relation to body constitution, sex, age and work capacity in the step test (Part 2)]. The stroke volume of the heart during exercise in upright position (steptest) was determined in 1500 Swiss children and adults of either sex, aged 5 to 65 years. The use of the simplified ergometric method (Strehler) allowed to carry out these determinations mainly in series and without any difficulty. Average absolute values are presented for each year during childhood and adolescence and for each decade in the period of adult life. The stroke volume is lower in the female than in the male group; this refers to absolute values as well as to values relative to body size. The absolute values are approximately proportional to body weight, to the cube of body height and to a standard volume calculated from body height and body weight. There is a typical age-depending course of the relationship between stroke volume and body size (standard volume), the development of the stroke volume showing a minimum before and a maximum during puberty. Provided work load in per cent of the maximal working capacity is the same the stroke volume of the heart during exercise in upright position remains unchanged until the age of about 55 to 60 years. The practical scope of the investigation was to collect data for the setting up of a new stroke volume standard."} {"id": "PMID:1258522", "title": "Excystation of Isospora arctopitheci Rodhain, 1933 with notes on a similiar process in Isospora begemina (Stiles, 1891) L\u00fche, 1906.", "content": "The in vitro excystation process of sporozoites of Isospora arctophitheci Rodhain, 1933 from the titi marmoset Saguinus geoffroyi and of Isospora bigemina (Stiles, 1891) L\u00fche, 1906 from the bobcat, Lynx rufus is presented. Sporocysts of both species lack a Stieda body and when exposed to a trypsin-sodium taurocholate (pH 7.4) excysting fluid the walls of both collapse in a similar fashion, along apparently predetermined lines. Similarities and differences on excystation between. I. arctopitheci, I. bigemina, and other Isospora, Eimeria, and Sarcocytis species are summarized. Such studies show that 2 distinct patterns of sporozoite excystation have been described to date, and both appear to be related to the structure of the sporocyst.", "contents": "Excystation of Isospora arctopitheci Rodhain, 1933 with notes on a similiar process in Isospora begemina (Stiles, 1891) L\u00fche, 1906. The in vitro excystation process of sporozoites of Isospora arctophitheci Rodhain, 1933 from the titi marmoset Saguinus geoffroyi and of Isospora bigemina (Stiles, 1891) L\u00fche, 1906 from the bobcat, Lynx rufus is presented. Sporocysts of both species lack a Stieda body and when exposed to a trypsin-sodium taurocholate (pH 7.4) excysting fluid the walls of both collapse in a similar fashion, along apparently predetermined lines. Similarities and differences on excystation between. I. arctopitheci, I. bigemina, and other Isospora, Eimeria, and Sarcocytis species are summarized. Such studies show that 2 distinct patterns of sporozoite excystation have been described to date, and both appear to be related to the structure of the sporocyst."} {"id": "PMID:1258523", "title": "Cytochemical detection of carbohydrates in the Golgi complex of Leptomonas pessoai.", "content": "Using the periodic acid-thiosemicarbazide-silver proteinate technique, a positive reaction was observed on the membranes of the Golgi complex of Leptomonas pessoai. A positive reaction was also observed in other cytoplasmic membranes located near the Golgi complex. Structures which could represent reserve polysaccharides were not observed in the cytoplasm of Leptomonas pessoai.", "contents": "Cytochemical detection of carbohydrates in the Golgi complex of Leptomonas pessoai. Using the periodic acid-thiosemicarbazide-silver proteinate technique, a positive reaction was observed on the membranes of the Golgi complex of Leptomonas pessoai. A positive reaction was also observed in other cytoplasmic membranes located near the Golgi complex. Structures which could represent reserve polysaccharides were not observed in the cytoplasm of Leptomonas pessoai."} {"id": "PMID:1258524", "title": "Comparative cytological studies of mitotic and male meiotic karyotype of Ascaridia dissimilis (Vigueras, 1931) and Ascaridia galli (Schrank, 1788).", "content": "Gametogony and spermatogenesis of A. dissimilis and A. galli were studied. It was found that the chromosome number of A. dissimilis is 2n = 10 for female specimens and 2n = 9 for male ones. The chromosome number of A. galli is also 2n = 10 for female specimens and 2n = 9 for males ones. Comparison of the relative length of chromosomes in the chromosome set, expressed in percentages, shows nearly equal magnitudes for both species. Spermatogenesis processes were studied. It was found that they run a similar course in both species. In the following stages of gametogony and spermatogenesis differences between the two species are not discovered.", "contents": "Comparative cytological studies of mitotic and male meiotic karyotype of Ascaridia dissimilis (Vigueras, 1931) and Ascaridia galli (Schrank, 1788). Gametogony and spermatogenesis of A. dissimilis and A. galli were studied. It was found that the chromosome number of A. dissimilis is 2n = 10 for female specimens and 2n = 9 for male ones. The chromosome number of A. galli is also 2n = 10 for female specimens and 2n = 9 for males ones. Comparison of the relative length of chromosomes in the chromosome set, expressed in percentages, shows nearly equal magnitudes for both species. Spermatogenesis processes were studied. It was found that they run a similar course in both species. In the following stages of gametogony and spermatogenesis differences between the two species are not discovered."} {"id": "PMID:1258525", "title": "On the karyotype of a laboratory Trichinella strain from Bulgaria.", "content": "The karyotype of male and female individuals of the species Trichinella nelsoni was studied. It was found that the number of chromosomes in females individuals is 2n = 6 and in males 2n = 5. Each pair of chromosomes differs from one another as to dimensions and location of the centromere. The univalent chromosome that was found in the chromosome set containing five chromosomes is the second largest submetacentric chromosome. It is suggested that this chromosome is the sex chromome of the studied Trichinellae.", "contents": "On the karyotype of a laboratory Trichinella strain from Bulgaria. The karyotype of male and female individuals of the species Trichinella nelsoni was studied. It was found that the number of chromosomes in females individuals is 2n = 6 and in males 2n = 5. Each pair of chromosomes differs from one another as to dimensions and location of the centromere. The univalent chromosome that was found in the chromosome set containing five chromosomes is the second largest submetacentric chromosome. It is suggested that this chromosome is the sex chromome of the studied Trichinellae."} {"id": "PMID:1258526", "title": "Ultrastructural studies of the cysticercoid of moniezia expansa (Anoplocephalidae) with special reference to the development of the cyst.", "content": "Cysticercoids of the sheep tapeworm Moniezia expansa have been grown in oribatid mites in the laboratory. Three species of mite became infected: Xenillus tegeocranus, Platynothrus peltifer and Euzetes globulus, the latter not previously recorded as a host of anoplocephalines. Cysticercoids aged 15 and 28 weeks were examined with the electron microscope. Four distinct types of cells were found in the 15-week cysticercoid. Subsequent cyst development involves a transformation from a cellular to a mainly fibrous structure. The fibres, arranged in three layers, resemble collagen fibres described elsewhere. The outer epidermis of the cyst is replaced by an amorphous, electron-dense outer coat whose nature is unknown. The inner part of the cyst becomes condensed to a myelin-like structure. The scolex develops features characteristic of the adult tapeworm.", "contents": "Ultrastructural studies of the cysticercoid of moniezia expansa (Anoplocephalidae) with special reference to the development of the cyst. Cysticercoids of the sheep tapeworm Moniezia expansa have been grown in oribatid mites in the laboratory. Three species of mite became infected: Xenillus tegeocranus, Platynothrus peltifer and Euzetes globulus, the latter not previously recorded as a host of anoplocephalines. Cysticercoids aged 15 and 28 weeks were examined with the electron microscope. Four distinct types of cells were found in the 15-week cysticercoid. Subsequent cyst development involves a transformation from a cellular to a mainly fibrous structure. The fibres, arranged in three layers, resemble collagen fibres described elsewhere. The outer epidermis of the cyst is replaced by an amorphous, electron-dense outer coat whose nature is unknown. The inner part of the cyst becomes condensed to a myelin-like structure. The scolex develops features characteristic of the adult tapeworm."} {"id": "PMID:1258527", "title": "Trace elements in Isoparorchis hypselobagri.", "content": "The trace elements contents of the tissue of Isoparorchis hypselobagri were ascertained by quantitative analyses. The iron content was found to be particularly high in comparison of copper and zinc.", "contents": "Trace elements in Isoparorchis hypselobagri. The trace elements contents of the tissue of Isoparorchis hypselobagri were ascertained by quantitative analyses. The iron content was found to be particularly high in comparison of copper and zinc."} {"id": "PMID:1258528", "title": "The effects of low temperature on Lymnaea truncatula.", "content": "A group of 20 young and another of 20 adult Lymnaea truncatula were abundantly supplied with food and kept continuously under cold conditions (5 degrees C) in the laboratory for 3 months and the effects of low temperature on their behavior, growth and reproduction were studied. The results indicate that at low temperature the activity of L. truncatula was markedly reduced but complete hibernation did not occur. The snails seem to be unaffected by the low temperature itself since none (both young and adult) died during the 3 months that they were kept at 5 degrees C. Reduced feeding, even in the presence of abundant food, during the cold conditions caused an almost total inhibiton of growth. Of even more significance was the suppression of reproduction which was connected with the metabolic rate of adult snails kept at low temperature. Young snails seem to profit by exposure to low temperature. On the return to normal laboratory temperature (16-22 degrees C) the young snails became very active, fed voraciously, grew rapidly, tended to live longer and produced more offspring than the controls. Low temperature, however, appears to have an adverse after-effect on the growth and reproduction of mature snails. Relatively, fewer eggs were deposited in this case. The results indicate that under natural field conditions in England, where temperature fluctuations during the usually mild winter months are common, the greater burden of increasing the population in overwintered snails must rest on the younger members of the community.", "contents": "The effects of low temperature on Lymnaea truncatula. A group of 20 young and another of 20 adult Lymnaea truncatula were abundantly supplied with food and kept continuously under cold conditions (5 degrees C) in the laboratory for 3 months and the effects of low temperature on their behavior, growth and reproduction were studied. The results indicate that at low temperature the activity of L. truncatula was markedly reduced but complete hibernation did not occur. The snails seem to be unaffected by the low temperature itself since none (both young and adult) died during the 3 months that they were kept at 5 degrees C. Reduced feeding, even in the presence of abundant food, during the cold conditions caused an almost total inhibiton of growth. Of even more significance was the suppression of reproduction which was connected with the metabolic rate of adult snails kept at low temperature. Young snails seem to profit by exposure to low temperature. On the return to normal laboratory temperature (16-22 degrees C) the young snails became very active, fed voraciously, grew rapidly, tended to live longer and produced more offspring than the controls. Low temperature, however, appears to have an adverse after-effect on the growth and reproduction of mature snails. Relatively, fewer eggs were deposited in this case. The results indicate that under natural field conditions in England, where temperature fluctuations during the usually mild winter months are common, the greater burden of increasing the population in overwintered snails must rest on the younger members of the community."} {"id": "PMID:1258545", "title": "[Cytophotometric DNA measurements in mononuclear round cells of synovial fluid].", "content": "Cytophotometric investigations were performed on synovial fluid mononuclear round cells in patients with various joint diseases. In nearly all instances only round cells with a diploid DNA-content were found. No increased proliferation could be observed neither in patients with rheumatoid arthritis nor in patients with a high relative number of neutrophilic granulocytes in the synovial fluid.", "contents": "[Cytophotometric DNA measurements in mononuclear round cells of synovial fluid]. Cytophotometric investigations were performed on synovial fluid mononuclear round cells in patients with various joint diseases. In nearly all instances only round cells with a diploid DNA-content were found. No increased proliferation could be observed neither in patients with rheumatoid arthritis nor in patients with a high relative number of neutrophilic granulocytes in the synovial fluid."} {"id": "PMID:1258547", "title": "[Isoelectric focusing studies of synovial fluid in rheumatoid arthritis].", "content": "Synovial fluids obtained at operation in several different diseases were studied by means of isoelectrical focussing. All the punctates of patients with rheumatoid arthritis showed bands which migrated towards the cathode and which were not found in synovial fluid from other diseases, except in 2 meniscus lesions. In the range of pH 6.81-7.30, typical synovial proteins were demonostrated.", "contents": "[Isoelectric focusing studies of synovial fluid in rheumatoid arthritis]. Synovial fluids obtained at operation in several different diseases were studied by means of isoelectrical focussing. All the punctates of patients with rheumatoid arthritis showed bands which migrated towards the cathode and which were not found in synovial fluid from other diseases, except in 2 meniscus lesions. In the range of pH 6.81-7.30, typical synovial proteins were demonostrated."} {"id": "PMID:1258548", "title": "[The course of adjuvant disease in rats of the strain AF/Han-EMD-SPF].", "content": "The development of articular and osseous lesions in AF/Han-EMD-SPF breed rats with adjuvant disease was studied by morphological methods. At the noninjected side arthritic lesions with eventual progressive joint destruction appeared about the tenth day after adjuvant injection. Nearly simultaneously an incipient tumorous osteomyelitis in the bones both of injected and non-injected side was observed. Since epitheloid granuloma were also seen in the periarticular tissue of some animals the authors believe that all lesions in adjuvant arthritis are caused by a widespread dissemination of the injected complete adjuvant.", "contents": "[The course of adjuvant disease in rats of the strain AF/Han-EMD-SPF]. The development of articular and osseous lesions in AF/Han-EMD-SPF breed rats with adjuvant disease was studied by morphological methods. At the noninjected side arthritic lesions with eventual progressive joint destruction appeared about the tenth day after adjuvant injection. Nearly simultaneously an incipient tumorous osteomyelitis in the bones both of injected and non-injected side was observed. Since epitheloid granuloma were also seen in the periarticular tissue of some animals the authors believe that all lesions in adjuvant arthritis are caused by a widespread dissemination of the injected complete adjuvant."} {"id": "PMID:1258562", "title": "[Abnormality in the behaviour of mice after an experimental encephalitis by yellow fever virus 17 D. Experiment model(author's transl)].", "content": "Viral encephalitides in infants are very often followed by serious mental manifestations. To be able experimentally to investigate this pathological phenomenon, we established the following model. Mice having recovered from an intracerebral infection with yellow fever virus 17 D (routine test for the potency of yellow fever vaccine) and giving the impression of normal and healthy animals were examined for their psychical behaviour. As unit of measurement we took the time for running through a labyrith (fig. 1). At the entrance of the labyrith in a box there was placed the population of animals of one cage (6 animals in maximum) and at the opposite side there was deposited the food. The animals going to be examined had been without food for 24 hours. The time was taken having passed from the moment of placing the animals up to the moment of their nibbing at the food. We examined 11 groups of mice having past routine tests for the potency of the yellow fever vaccine. One of them had been tested twice at an interval of 54 days (table 1). The 791 mice which had passed the encephalitic infection showed an average running time of 8.90 min. The 164 controls, however, had an average running time of 4.37 min (table 2). This difference is significant (p=greater than 1/1000). The average running time is proportional to the injected virus quantity (table 3). The significance of each single virus dilution to the group of normal animals is always greater than 1/1000. The significance is more than 1/100 for each single virus dilution between 10(-1) and 10(-3) compared with the virus dilution of 10(-5). Immediately after the clinical period (21 days), no difference could be observed between the single virus dilutions. After 76 days only, the test showed the above mentioned differences (table 4). Therefore, the mice having found their food after a long running time had more serious postencephalitic lesions than those having had a shorter running time. To prove this statement, we examined histologically brains of 14 mice which had found their food after 20 min on an average and those of 16 mice having had an average running time of 6.58 min. The histological evaluation was performed in regard to eight pathological characteristica. The results were recorded on tables for each slide with a histological preparation. For this we used squared paper (fig. 2, 3). For each brain of mice, the so-called \"index of lesions\" was calculated by the proportion of labelled and all squares. .....", "contents": "[Abnormality in the behaviour of mice after an experimental encephalitis by yellow fever virus 17 D. Experiment model(author's transl)]. Viral encephalitides in infants are very often followed by serious mental manifestations. To be able experimentally to investigate this pathological phenomenon, we established the following model. Mice having recovered from an intracerebral infection with yellow fever virus 17 D (routine test for the potency of yellow fever vaccine) and giving the impression of normal and healthy animals were examined for their psychical behaviour. As unit of measurement we took the time for running through a labyrith (fig. 1). At the entrance of the labyrith in a box there was placed the population of animals of one cage (6 animals in maximum) and at the opposite side there was deposited the food. The animals going to be examined had been without food for 24 hours. The time was taken having passed from the moment of placing the animals up to the moment of their nibbing at the food. We examined 11 groups of mice having past routine tests for the potency of the yellow fever vaccine. One of them had been tested twice at an interval of 54 days (table 1). The 791 mice which had passed the encephalitic infection showed an average running time of 8.90 min. The 164 controls, however, had an average running time of 4.37 min (table 2). This difference is significant (p=greater than 1/1000). The average running time is proportional to the injected virus quantity (table 3). The significance of each single virus dilution to the group of normal animals is always greater than 1/1000. The significance is more than 1/100 for each single virus dilution between 10(-1) and 10(-3) compared with the virus dilution of 10(-5). Immediately after the clinical period (21 days), no difference could be observed between the single virus dilutions. After 76 days only, the test showed the above mentioned differences (table 4). Therefore, the mice having found their food after a long running time had more serious postencephalitic lesions than those having had a shorter running time. To prove this statement, we examined histologically brains of 14 mice which had found their food after 20 min on an average and those of 16 mice having had an average running time of 6.58 min. The histological evaluation was performed in regard to eight pathological characteristica. The results were recorded on tables for each slide with a histological preparation. For this we used squared paper (fig. 2, 3). For each brain of mice, the so-called \"index of lesions\" was calculated by the proportion of labelled and all squares. ....."} {"id": "PMID:1258563", "title": "[Newer antimycotics. II. Arylhydrazones of derivatives of mesoxalic acid (author's transl)].", "content": "The author produced a number of aryl-hydrazone-derivatives of the esters and amides of mesoxalic-acid-seminitril and of mesoxalic-acid-diethylester, investigated their fungistatic efficiency in vitro, and discussed the association of chemical structure with the fungistatic effect in the series of these compounds. From the author's results it can be concluded that some compounds from the series of the aryl-hydrazones of mesoxalic-acid-seminitril-esters exert a strong fungistatic effect on Trichophyton gyps. (Tabl. 1); namely those, whose ester-alkyl-group is relatively short and in that there are the substituents of benzolring Cl-atom, CH3- or NO2- groups. On the other hand the majority of the compounds of this series is totally ineffective (Tab. 2). Each aryl-hydrazones of the amides of mesoxalic-acid-seminitril ant that ones of the mesoxalic-acid-diethylester are ineffective on Trichophyton gyps. (Tab. 2, 4, 5). Not a compound of the investigated series exerts any fungistatic effect on fungi-strains other then Trichophyton gyps. Those aryl-hydrazones of the mesoxalic-acid-seminitrilesters, which proved to be most effective on Trichophyton gyps. are on the mouse only negligible toxic and they do not irritate the skin and mucous membranes of the experimental animals; their fungistatic effect is not influenced by cystein, cysteamin or thioglycolic-acid. On the basis of the intensive fungistatic efficiency and small toxicity of some aryl-hydrazones of the mesoxalic-acid-seminitril-esters, it seems that a number of representatives of these types of chemical compounds could be given a role in the chemotherapy of superficial human and animal dermatomycoses.", "contents": "[Newer antimycotics. II. Arylhydrazones of derivatives of mesoxalic acid (author's transl)]. The author produced a number of aryl-hydrazone-derivatives of the esters and amides of mesoxalic-acid-seminitril and of mesoxalic-acid-diethylester, investigated their fungistatic efficiency in vitro, and discussed the association of chemical structure with the fungistatic effect in the series of these compounds. From the author's results it can be concluded that some compounds from the series of the aryl-hydrazones of mesoxalic-acid-seminitril-esters exert a strong fungistatic effect on Trichophyton gyps. (Tabl. 1); namely those, whose ester-alkyl-group is relatively short and in that there are the substituents of benzolring Cl-atom, CH3- or NO2- groups. On the other hand the majority of the compounds of this series is totally ineffective (Tab. 2). Each aryl-hydrazones of the amides of mesoxalic-acid-seminitril ant that ones of the mesoxalic-acid-diethylester are ineffective on Trichophyton gyps. (Tab. 2, 4, 5). Not a compound of the investigated series exerts any fungistatic effect on fungi-strains other then Trichophyton gyps. Those aryl-hydrazones of the mesoxalic-acid-seminitrilesters, which proved to be most effective on Trichophyton gyps. are on the mouse only negligible toxic and they do not irritate the skin and mucous membranes of the experimental animals; their fungistatic effect is not influenced by cystein, cysteamin or thioglycolic-acid. On the basis of the intensive fungistatic efficiency and small toxicity of some aryl-hydrazones of the mesoxalic-acid-seminitril-esters, it seems that a number of representatives of these types of chemical compounds could be given a role in the chemotherapy of superficial human and animal dermatomycoses."} {"id": "PMID:1258564", "title": "[Possible relationship between bacterial surface structures, immune-adherence, chemotaxis and phagocytosis (author's transl)].", "content": "In the present study we attempted to determine the relationship between bacterial surface structures, immune adherence, chemotaxis and phagocytosis. As shown in table 1 encapsulated bacteria (Klebsiella ozanae, K. pneumoniae, Pasteurella multocida, Streptococcus pneumoniae), Mycoplasma pneumoniae and M. fermentans had a much lower immune adherence-activity than non-encapsulated bacteria (Bacillus cereus, Brucella abortus, Erysipelothrix insidiosa, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella typhimurium, S. typhi). Consequently, the former bacteria, in the absece of specific antibodies, activated complement via the C-3-bypass to a smaller extent than the latter. In modified Boyden chambers the encapsulated bacteria and the mycoplasmas were much less cytotaxigenic than the non-encapsulated bacteria (table 3). Corresponding to this was the chemotactic response in vivo. Finally the rates of phagocytosis were considerably lower with the encapsulated bacteria than with the non-encapsulated ones (fig. 1).", "contents": "[Possible relationship between bacterial surface structures, immune-adherence, chemotaxis and phagocytosis (author's transl)]. In the present study we attempted to determine the relationship between bacterial surface structures, immune adherence, chemotaxis and phagocytosis. As shown in table 1 encapsulated bacteria (Klebsiella ozanae, K. pneumoniae, Pasteurella multocida, Streptococcus pneumoniae), Mycoplasma pneumoniae and M. fermentans had a much lower immune adherence-activity than non-encapsulated bacteria (Bacillus cereus, Brucella abortus, Erysipelothrix insidiosa, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella typhimurium, S. typhi). Consequently, the former bacteria, in the absece of specific antibodies, activated complement via the C-3-bypass to a smaller extent than the latter. In modified Boyden chambers the encapsulated bacteria and the mycoplasmas were much less cytotaxigenic than the non-encapsulated bacteria (table 3). Corresponding to this was the chemotactic response in vivo. Finally the rates of phagocytosis were considerably lower with the encapsulated bacteria than with the non-encapsulated ones (fig. 1)."} {"id": "PMID:1258565", "title": "[Field studies with a new tick-borne encephalitis (TBE) vaccine].", "content": "The vaccine used contained formalin-inactivated TBE virus that was grown in chick embryo cells and adsorbed to Alhydrogel. In a first study, conducted in 1973, a total of 81 volunteers were given subcutaneously two doses of vaccine 4 weeks apart, and a third dose 7-9 months later. After each vaccination, the rates of seroconversion were assayed in the hemagglutination inhibition test. The values obtained were 76%, 96% and 98%, respectively. The geometric mean titers found were 1:26, 1:36 and 1:44. The vaccine was well tolerated locally and systematic reactions such as fever headache and fatigue were only recorded after the first dose of vaccine. In 1974 and 1975 a total of 30,000 persons were vaccinated in areas where the disease is endemic. Most of the vaccinees work in forests and are, therefore, at high risk of infection. Circumstantial evidence indicates that the vaccine is protective.", "contents": "[Field studies with a new tick-borne encephalitis (TBE) vaccine]. The vaccine used contained formalin-inactivated TBE virus that was grown in chick embryo cells and adsorbed to Alhydrogel. In a first study, conducted in 1973, a total of 81 volunteers were given subcutaneously two doses of vaccine 4 weeks apart, and a third dose 7-9 months later. After each vaccination, the rates of seroconversion were assayed in the hemagglutination inhibition test. The values obtained were 76%, 96% and 98%, respectively. The geometric mean titers found were 1:26, 1:36 and 1:44. The vaccine was well tolerated locally and systematic reactions such as fever headache and fatigue were only recorded after the first dose of vaccine. In 1974 and 1975 a total of 30,000 persons were vaccinated in areas where the disease is endemic. Most of the vaccinees work in forests and are, therefore, at high risk of infection. Circumstantial evidence indicates that the vaccine is protective."} {"id": "PMID:1258567", "title": "[Clinical and histopathological findings in mycoplasmal polyarthritis of rats. III. Course of infection during the weeks 7-30 and 54-61 (author's transl)].", "content": "Clinical, microbiological and histological findings of the late phase of experimentally induced Mycoplasma-polyarthritis in rats are described. Investigations were carried out between the 7.-30. week and between the 54-61. week p.i. M. arthritidis could be reisolated from affected joints regularly up to the 7th week p.i. Thereafter until 12th week only occasional recovery was possible. The healing process of affected joints dominated signs of arthritis which could be confirmed histologically as a purulent process. The alterations of carpal and tarsal joints were divided into purulent, chronic deforming and chronic minor lesions. The findings derived from investigation of joints and parenchymatous organs during the course of the disease are discussed.", "contents": "[Clinical and histopathological findings in mycoplasmal polyarthritis of rats. III. Course of infection during the weeks 7-30 and 54-61 (author's transl)]. Clinical, microbiological and histological findings of the late phase of experimentally induced Mycoplasma-polyarthritis in rats are described. Investigations were carried out between the 7.-30. week and between the 54-61. week p.i. M. arthritidis could be reisolated from affected joints regularly up to the 7th week p.i. Thereafter until 12th week only occasional recovery was possible. The healing process of affected joints dominated signs of arthritis which could be confirmed histologically as a purulent process. The alterations of carpal and tarsal joints were divided into purulent, chronic deforming and chronic minor lesions. The findings derived from investigation of joints and parenchymatous organs during the course of the disease are discussed."} {"id": "PMID:1258591", "title": "[Distant metastases in carcinomas of the upper airways and digestive tract (author's transl)].", "content": "144 patients with a carcinoma of the upper airways and digestive tract were examined at necropsy in the Institut Bordet, between January 1, 1960 and December 31, 1973. The study shows that 43% of these patients had distant metastases and that among these 2/3 were in local recurrence. Only 1/4 of the metastases had been recognized before death: most of them appearing in the first year following the diagnosis of the primary tumor. Survival of patients with metastases is short, most of them dying within 3 months after metastatic discovery. There seems to be no evident relationship between the initial degree of extension of the tumor and the risk of later metastatic dissemination. In the search for the most frequent metastases, located in the lungs, liver and skeleton, one should use pulmonary laminography and liver tests combined to scanning and laparoscopy.", "contents": "[Distant metastases in carcinomas of the upper airways and digestive tract (author's transl)]. 144 patients with a carcinoma of the upper airways and digestive tract were examined at necropsy in the Institut Bordet, between January 1, 1960 and December 31, 1973. The study shows that 43% of these patients had distant metastases and that among these 2/3 were in local recurrence. Only 1/4 of the metastases had been recognized before death: most of them appearing in the first year following the diagnosis of the primary tumor. Survival of patients with metastases is short, most of them dying within 3 months after metastatic discovery. There seems to be no evident relationship between the initial degree of extension of the tumor and the risk of later metastatic dissemination. In the search for the most frequent metastases, located in the lungs, liver and skeleton, one should use pulmonary laminography and liver tests combined to scanning and laparoscopy."} {"id": "PMID:1258593", "title": "[Colon occlusion due to safety belt (authors transl)].", "content": "The author describes a delayed occlusion of the colon, consecutive to an ischemic constriction, occurring after a car accident in a patient wearing his safety belt. The patient, 49 years old, had undergone urgent laparotomy just after the accident: intraabdominal hemorrhage from hepatic and mesocolic lacerations were discovered and treated. Six weeks after that operation the patient developed an occlusion of the transverse colon necessitating segmental resection and end-to-end anastomosis. Pathology disclosed typical signs of ischemia with constriction. This was considered due to the horizontal part of the safety belt. This should be placed low and tight enough so that the pelvis, rather than the abdominal viscera, receives the shock. After accidents with safety belts the possibility of such complications should be present at mind.", "contents": "[Colon occlusion due to safety belt (authors transl)]. The author describes a delayed occlusion of the colon, consecutive to an ischemic constriction, occurring after a car accident in a patient wearing his safety belt. The patient, 49 years old, had undergone urgent laparotomy just after the accident: intraabdominal hemorrhage from hepatic and mesocolic lacerations were discovered and treated. Six weeks after that operation the patient developed an occlusion of the transverse colon necessitating segmental resection and end-to-end anastomosis. Pathology disclosed typical signs of ischemia with constriction. This was considered due to the horizontal part of the safety belt. This should be placed low and tight enough so that the pelvis, rather than the abdominal viscera, receives the shock. After accidents with safety belts the possibility of such complications should be present at mind."} {"id": "PMID:1258597", "title": "Iron deposits in chronic alcoholics. Special studies in relation to the iron contained in red wine.", "content": "The iron deposits in 52 persons with marked chronic alcoholism, almost all from wine, have been studied. No relationship was found between the level of the deposits and the quantity of iron ingested by the alcoholic with the beverage. We point out the influence that alcohol may have on iron deposits. A critical examination was also made of the methods for determining organic reserves of iron.", "contents": "Iron deposits in chronic alcoholics. Special studies in relation to the iron contained in red wine. The iron deposits in 52 persons with marked chronic alcoholism, almost all from wine, have been studied. No relationship was found between the level of the deposits and the quantity of iron ingested by the alcoholic with the beverage. We point out the influence that alcohol may have on iron deposits. A critical examination was also made of the methods for determining organic reserves of iron."} {"id": "PMID:1258598", "title": "Serum levels of C3 and cholinesterase in various diseases of the liver.", "content": "The levels of C3, cholinesterase, albumin and prothrombin were determined in 46 patients (27 males and 19 females) - 26 with cirrhosis of the liver, 9 with acute hepatitis, 6 with chronic aggressive hepatitis, 1 with chronic persistent hepatitis and 4 with fatty liver. In all patients and, particularly in those with cirrhotic liver, it was shown that the normal or pathological level of serum C 3 is related both qualitatively and quantitatively to the normal or pathological levels of cholinesterase, albumin, and prothrombin. The percentage in which the levels of these four parameters were pathological was considerably higher in the cases with hepatic coma than in the cases without hepatic coma. The determination of the range of confidence for the 4 parameters showed that, in the patients with hepatic coma, cholinesterase reacted most sensitively to liver damage (0.5 - 0.94) followed by C3 and prothrombin (0.33 - 0.81). Also in the cases without hepatic coma, cholinesterase was the most sensitive indicator (0.05 - 0.29), followed by prothrombin (0.03 - 0.24), albumin and C3 (0.00-0.16).", "contents": "Serum levels of C3 and cholinesterase in various diseases of the liver. The levels of C3, cholinesterase, albumin and prothrombin were determined in 46 patients (27 males and 19 females) - 26 with cirrhosis of the liver, 9 with acute hepatitis, 6 with chronic aggressive hepatitis, 1 with chronic persistent hepatitis and 4 with fatty liver. In all patients and, particularly in those with cirrhotic liver, it was shown that the normal or pathological level of serum C 3 is related both qualitatively and quantitatively to the normal or pathological levels of cholinesterase, albumin, and prothrombin. The percentage in which the levels of these four parameters were pathological was considerably higher in the cases with hepatic coma than in the cases without hepatic coma. The determination of the range of confidence for the 4 parameters showed that, in the patients with hepatic coma, cholinesterase reacted most sensitively to liver damage (0.5 - 0.94) followed by C3 and prothrombin (0.33 - 0.81). Also in the cases without hepatic coma, cholinesterase was the most sensitive indicator (0.05 - 0.29), followed by prothrombin (0.03 - 0.24), albumin and C3 (0.00-0.16)."} {"id": "PMID:1258599", "title": "Effects of fructose infusions in patients suffering from acute viral hepatitis.", "content": "Two groups of patients suffering from uncomplicated viral hepatitis were treated for seven consecutive days with intravenous infusions of fructose and glucose, respectively (1 gram per kilogram body weight per diem). Serum transaminases were determined daily as were total bilirubin and uric acid levels. No statistically significant variations in the values of these tests were observed between the two groups of patients. Serum lactic and pyruvic acid concentrations were also determined both before and after infusion during the first three days of treatment. Blood lactic and pyruvic acid levels were found to rise significantly after fructose infusion, but not after glucose infusion. These changes, however, were limited and did not affect the lactate/pyruvate ratio.", "contents": "Effects of fructose infusions in patients suffering from acute viral hepatitis. Two groups of patients suffering from uncomplicated viral hepatitis were treated for seven consecutive days with intravenous infusions of fructose and glucose, respectively (1 gram per kilogram body weight per diem). Serum transaminases were determined daily as were total bilirubin and uric acid levels. No statistically significant variations in the values of these tests were observed between the two groups of patients. Serum lactic and pyruvic acid concentrations were also determined both before and after infusion during the first three days of treatment. Blood lactic and pyruvic acid levels were found to rise significantly after fructose infusion, but not after glucose infusion. These changes, however, were limited and did not affect the lactate/pyruvate ratio."} {"id": "PMID:1258600", "title": "Influence of d-galactosamine hydrochloride on lipids and their fatty acid composition in plasma and liver of guinea pigs.", "content": "48 hrs after i.v. applications of 1 g/kg b.w. galactosamine hydrochloride to guinea pigs the total lipids of plasma, liver homogenate and isolated liver microsomes were extracted and separated by dialysis and thin-layer chromatography. The fatty acid fractions of total lipids (plasma), neutral lipids and total phospholipids (liver homogenate) as well as phosphatidylcholines and remaining phospholipids (liver microsomes) were analyzed by gaschromatography. In plasma the concentration of total lipids was unchanged in the galactosamine group. A slight decrease of the C16- and an increase of the C161- fatty acids were observed. In total liver homogenate neutral lipids increased 9-fold, and phospholipids 2.5 fold after galactosamine application. Specially there was a relative and absolute increase of the C16-, C16(1)-, C18(1)-, and C18(3)-fatty acids in the neutral lipids, whereas the C18- and C18(2)-Fatty acids were relatively diminished. Similar changes within the fatty acid fractions could be found to a minor degree in the phospholipids. 48 hours after application of galactosamine the phospholipid content in isolated liver microsomes increased about 2-fold. Likewise there was an absolute increase of nearly all fatty acid fractions as well in phosphatidylcholines as in the other phospholipids. In both phospholipid fractions the percentage of the C18-fatty acids decreased and a relative increase in C16-fatty acids was observed. Contrary to the findings in total liver, in the isolated microsomes predominantly saturated fatty acids (C16, C18) were found.", "contents": "Influence of d-galactosamine hydrochloride on lipids and their fatty acid composition in plasma and liver of guinea pigs. 48 hrs after i.v. applications of 1 g/kg b.w. galactosamine hydrochloride to guinea pigs the total lipids of plasma, liver homogenate and isolated liver microsomes were extracted and separated by dialysis and thin-layer chromatography. The fatty acid fractions of total lipids (plasma), neutral lipids and total phospholipids (liver homogenate) as well as phosphatidylcholines and remaining phospholipids (liver microsomes) were analyzed by gaschromatography. In plasma the concentration of total lipids was unchanged in the galactosamine group. A slight decrease of the C16- and an increase of the C161- fatty acids were observed. In total liver homogenate neutral lipids increased 9-fold, and phospholipids 2.5 fold after galactosamine application. Specially there was a relative and absolute increase of the C16-, C16(1)-, C18(1)-, and C18(3)-fatty acids in the neutral lipids, whereas the C18- and C18(2)-Fatty acids were relatively diminished. Similar changes within the fatty acid fractions could be found to a minor degree in the phospholipids. 48 hours after application of galactosamine the phospholipid content in isolated liver microsomes increased about 2-fold. Likewise there was an absolute increase of nearly all fatty acid fractions as well in phosphatidylcholines as in the other phospholipids. In both phospholipid fractions the percentage of the C18-fatty acids decreased and a relative increase in C16-fatty acids was observed. Contrary to the findings in total liver, in the isolated microsomes predominantly saturated fatty acids (C16, C18) were found."} {"id": "PMID:1258601", "title": "Esophageal function in progressive systemic sclerosis.", "content": "A prospective study was performed in 13 consecutive patients with systemic progressive sclerosis (PSS). For the diagnosis of impaired esophageal peristalsis cineradiography and manometry are equally useful. Esophageal suction biopsy allows the diagnosis of esophagitis but not of scleroderma. Mild to severe esophageal involvement was observed in 12 patients. In only one patient the esophagus was virtually normal. Dysfunction of the esophageal body may occur early in the course of the disease while incompetence of the lower esophageal sphincter is observed on an average after 7 to 8 years. Both impairment of peristalsis and pressure of the lower esophageal sphincter may lead to delayed esophageal clearance. Relaxation of LES is normal even in the absence of primary peristalsis. Extensive esophageal damage including severe gastroesophageal reflux may be present in the absence of esophageal symptoms.", "contents": "Esophageal function in progressive systemic sclerosis. A prospective study was performed in 13 consecutive patients with systemic progressive sclerosis (PSS). For the diagnosis of impaired esophageal peristalsis cineradiography and manometry are equally useful. Esophageal suction biopsy allows the diagnosis of esophagitis but not of scleroderma. Mild to severe esophageal involvement was observed in 12 patients. In only one patient the esophagus was virtually normal. Dysfunction of the esophageal body may occur early in the course of the disease while incompetence of the lower esophageal sphincter is observed on an average after 7 to 8 years. Both impairment of peristalsis and pressure of the lower esophageal sphincter may lead to delayed esophageal clearance. Relaxation of LES is normal even in the absence of primary peristalsis. Extensive esophageal damage including severe gastroesophageal reflux may be present in the absence of esophageal symptoms."} {"id": "PMID:1258602", "title": "The entity of non occlusive mesenteric ischemia: strophanthin effect on mesenteric blood flow in experimental animals.", "content": "Digitalis glycosides have the well known positive inotropic effect on the heart. Their effect on extracardiac vascular smooth muscle receives increasing attention. In experimental animals a significant decrease in mesenteric blood flow and an increase in mesenteric vascular resistance could be shown. Angiography of main mesenteric arteries, smaller arteries, and arterioles reveal typical vasoconstriction. Angiomorphometric measurements show good correlation between the decrease in vascular diameter and the increase in vascular resistance.", "contents": "The entity of non occlusive mesenteric ischemia: strophanthin effect on mesenteric blood flow in experimental animals. Digitalis glycosides have the well known positive inotropic effect on the heart. Their effect on extracardiac vascular smooth muscle receives increasing attention. In experimental animals a significant decrease in mesenteric blood flow and an increase in mesenteric vascular resistance could be shown. Angiography of main mesenteric arteries, smaller arteries, and arterioles reveal typical vasoconstriction. Angiomorphometric measurements show good correlation between the decrease in vascular diameter and the increase in vascular resistance."} {"id": "PMID:1258603", "title": "Multiple dermal perifollicular fibromas with polyps of the colon -- report of a peculiar clinical syndrome.", "content": "In the present study, a peculiar fibromatosis cutis in two siblings has been reported, the dermatosis being characterized by innumerable perifollicular fibromas on face, neck and trunk as well as multiple fibromata pendulantia. Since the father allegedly had skin lesions resembling those of his two affected children, an inherited condition is assumed for the disease which manifests itself rather late in age. In the female patient, several adenomatous colon polyps were found, one transformed into an incipient carcinoma. Since the clinical and dermatohistological features are anything but typical of Gardner's syndrome and, in particular, hamartomalike fibromas of the perifollicular hair sheath are not constituents of its well-known skin tumour complex, we have discussed in detail the possibility of a peculiar cutaneo-intestinal syndrome hitherto unknown.", "contents": "Multiple dermal perifollicular fibromas with polyps of the colon -- report of a peculiar clinical syndrome. In the present study, a peculiar fibromatosis cutis in two siblings has been reported, the dermatosis being characterized by innumerable perifollicular fibromas on face, neck and trunk as well as multiple fibromata pendulantia. Since the father allegedly had skin lesions resembling those of his two affected children, an inherited condition is assumed for the disease which manifests itself rather late in age. In the female patient, several adenomatous colon polyps were found, one transformed into an incipient carcinoma. Since the clinical and dermatohistological features are anything but typical of Gardner's syndrome and, in particular, hamartomalike fibromas of the perifollicular hair sheath are not constituents of its well-known skin tumour complex, we have discussed in detail the possibility of a peculiar cutaneo-intestinal syndrome hitherto unknown."} {"id": "PMID:1258606", "title": "Evidence for the involvement of vasoactive constitutents of mast cells in axon reflex vasodilatation in the skin of the rat.", "content": "Axon reflex vasodilation following injury to the skin of the pinna of the ear was studied in rats by a thermometric method. Post-traumatic vaso-dilatation did not occur in animals treated with tyrosine ethyl ester, an inhibitor of chymotrypsin. Vasodilatation was not affected by treatment of the rats with chlorpheniramine (antihistamine) or cyproheptadine (antihistamine and anti-serotinin) or with aprotinin, soybean trypsin inhibitor, epsilon-aminocaproic acid or tosyl arginine methyl ester (inhibitors of trypsin and of some other proteinases). Taken in conjunction with the results of other investigations, these findings indicate that in the skin of the rat: (a) histamine and serotinin are not essential for the initiation of axon reflexes, and (b) the chymotrypsin-like proteinase of mast cell granules, released as the result of antidromic activity in sensory axons, may act as a kininogenase and be responsible for causing dilatation of arterioles at the efferent limb of the axon reflex.", "contents": "Evidence for the involvement of vasoactive constitutents of mast cells in axon reflex vasodilatation in the skin of the rat. Axon reflex vasodilation following injury to the skin of the pinna of the ear was studied in rats by a thermometric method. Post-traumatic vaso-dilatation did not occur in animals treated with tyrosine ethyl ester, an inhibitor of chymotrypsin. Vasodilatation was not affected by treatment of the rats with chlorpheniramine (antihistamine) or cyproheptadine (antihistamine and anti-serotinin) or with aprotinin, soybean trypsin inhibitor, epsilon-aminocaproic acid or tosyl arginine methyl ester (inhibitors of trypsin and of some other proteinases). Taken in conjunction with the results of other investigations, these findings indicate that in the skin of the rat: (a) histamine and serotinin are not essential for the initiation of axon reflexes, and (b) the chymotrypsin-like proteinase of mast cell granules, released as the result of antidromic activity in sensory axons, may act as a kininogenase and be responsible for causing dilatation of arterioles at the efferent limb of the axon reflex."} {"id": "PMID:1258607", "title": "Neuropathological considerations in cerebro-hepato-renal syndrome (Zellweger's syndrome).", "content": "The nervous system in patients with cerebro-hepato-renal syndrome appeared to be affected at various tissue levels. There was evidence of a migrational disorder manifested by polymicrogyria and lack of normal neuronal maturation. There was dysmyelination of the white matter associated with accumulation of neutral fat in astrocytes. Within the peripheral nerves, masses of tangled neurofilaments producing dystrophic axons were demonstrated by electron microscopy. These findings could be explained on the basis of a genetic metabolic defect, one that involved particularly the amino acids. The defect may have interfered with the normal intercellular reaction during embryogenesis resulting in the malformation of multiple organs. The same metabolic abnormality could have caused the hepatic damage and disturbance in normal myelination during the neonatal period.", "contents": "Neuropathological considerations in cerebro-hepato-renal syndrome (Zellweger's syndrome). The nervous system in patients with cerebro-hepato-renal syndrome appeared to be affected at various tissue levels. There was evidence of a migrational disorder manifested by polymicrogyria and lack of normal neuronal maturation. There was dysmyelination of the white matter associated with accumulation of neutral fat in astrocytes. Within the peripheral nerves, masses of tangled neurofilaments producing dystrophic axons were demonstrated by electron microscopy. These findings could be explained on the basis of a genetic metabolic defect, one that involved particularly the amino acids. The defect may have interfered with the normal intercellular reaction during embryogenesis resulting in the malformation of multiple organs. The same metabolic abnormality could have caused the hepatic damage and disturbance in normal myelination during the neonatal period."} {"id": "PMID:1258608", "title": "Extravasation, spread and cellular uptake of Evans blue-labelled albumin around a reproducible small stab-wound in the rat brain.", "content": "A small stab wound was made in the frontal lobe of the rat brain in order to study both the acute damage and the restitution of the blood-brain barrier to macromolecules under well-defined experimental conditions. Intravenously administered Evans blue-labelled albumin (EBA) was used as a tracer and the brain sections were observed in a fluorescence microscope. EBA leaked into the neuropil only during the first 3 days after the trauma. The maximal leakage occurred during the first day after the injury. The tracer spread from the area surrounding the stab wound in a reproducible way, initially roughly centrifugally. Nerve and glial cells close to the wound displayed a diffuse fluorescence of their cell bodies 1 to 6 h after the injury, i.e. at times with maximal extravasation of the tracer. A more granular distribution of the tracer was seen in neurons and glial cells at both very short and long times after EBA injection. Thus, the blood-brain barrier lesion induced was reproducible and reversible as judged by the pattern of EBA leakage. Some cells immediately adjacent to the injury had a diffuse cytoplasmic distribution of the tracer complex, in contrast to cells more distant from the injury, having a more granular distribution of the tracer in their cytoplasm. However, the appearance of the fluorescence in neurons and glia was to a large extent dependent upon the time after the injury, at which the cells were exposed to the tracer complex and on the time that had elapsed from the time of injection of the tracer complex to the sacrifice of the animal. Thus, it seems likely that two factors contribute to the appearance of the neuronal EBA distribution: on one hand the location and possibly extent of cellular damage of the cell, and, on the other hand, the time and amount of EBA to which the cells were exposed.", "contents": "Extravasation, spread and cellular uptake of Evans blue-labelled albumin around a reproducible small stab-wound in the rat brain. A small stab wound was made in the frontal lobe of the rat brain in order to study both the acute damage and the restitution of the blood-brain barrier to macromolecules under well-defined experimental conditions. Intravenously administered Evans blue-labelled albumin (EBA) was used as a tracer and the brain sections were observed in a fluorescence microscope. EBA leaked into the neuropil only during the first 3 days after the trauma. The maximal leakage occurred during the first day after the injury. The tracer spread from the area surrounding the stab wound in a reproducible way, initially roughly centrifugally. Nerve and glial cells close to the wound displayed a diffuse fluorescence of their cell bodies 1 to 6 h after the injury, i.e. at times with maximal extravasation of the tracer. A more granular distribution of the tracer was seen in neurons and glial cells at both very short and long times after EBA injection. Thus, the blood-brain barrier lesion induced was reproducible and reversible as judged by the pattern of EBA leakage. Some cells immediately adjacent to the injury had a diffuse cytoplasmic distribution of the tracer complex, in contrast to cells more distant from the injury, having a more granular distribution of the tracer in their cytoplasm. However, the appearance of the fluorescence in neurons and glia was to a large extent dependent upon the time after the injury, at which the cells were exposed to the tracer complex and on the time that had elapsed from the time of injection of the tracer complex to the sacrifice of the animal. Thus, it seems likely that two factors contribute to the appearance of the neuronal EBA distribution: on one hand the location and possibly extent of cellular damage of the cell, and, on the other hand, the time and amount of EBA to which the cells were exposed."} {"id": "PMID:1258609", "title": "Autoradiographic localisation of 3H-uridine in spinal ganglion neurones of the rat and the effects of methyl mercury poisoning.", "content": "The uptake of 3H-uridine into rat spinal ganglion neurones has been followed by autoradiography for up to 48 h after its intravenous injection. Labelling of nucleoli and of nuclei reached a peak within 1 h and then declined. Nuclear labelling returned to background levels by 24 h, but nucleolar labelling was still significant after 48 h. Animals dosed with methyl mercury chloride (7.5 mg/kg daily) showed no change in labelling rate in nucleolus or nucleus after 1, 2, or 4 doses. After 8 doses there was severe reduction in labelling in both nucleolus and nucleus; this amount causes extensive loss of axons, loss of some cell bodies and a marked reduction in amino acid incorporation into proteins. On recovery after a further 8 days, labelling levels returned to normal. It is concluded that at the time when loss of ribosomes occurs from the cytoplasm methyl mercury is more likely to be directly disturbing ribosomal structure than RNA synthesis, for methyl mercury causes marked changes in ribosomal organisation after 4 doses, but disturbances to RNA synthesis do not occur until the 8th dose.", "contents": "Autoradiographic localisation of 3H-uridine in spinal ganglion neurones of the rat and the effects of methyl mercury poisoning. The uptake of 3H-uridine into rat spinal ganglion neurones has been followed by autoradiography for up to 48 h after its intravenous injection. Labelling of nucleoli and of nuclei reached a peak within 1 h and then declined. Nuclear labelling returned to background levels by 24 h, but nucleolar labelling was still significant after 48 h. Animals dosed with methyl mercury chloride (7.5 mg/kg daily) showed no change in labelling rate in nucleolus or nucleus after 1, 2, or 4 doses. After 8 doses there was severe reduction in labelling in both nucleolus and nucleus; this amount causes extensive loss of axons, loss of some cell bodies and a marked reduction in amino acid incorporation into proteins. On recovery after a further 8 days, labelling levels returned to normal. It is concluded that at the time when loss of ribosomes occurs from the cytoplasm methyl mercury is more likely to be directly disturbing ribosomal structure than RNA synthesis, for methyl mercury causes marked changes in ribosomal organisation after 4 doses, but disturbances to RNA synthesis do not occur until the 8th dose."} {"id": "PMID:1258610", "title": "Murine influenza virus encephalomyelitis. III. Effect of defective interfering virus particles.", "content": "Defective interfering influenza virus particles lessened the yield of infective virus recovered from brain after intracerebral challange of 3-week old mice, but failed to affect the appearance of disease or lethality. In 7-week old mice, the presence of defective interfering influenza virus particles reduced both lethality and virus yield. Viral inocula containing significant numbers of defective particles appeared to diminish later inflammatory changes, nerve cell degeneration and the appearance of viral antigen in deeper cerebral regions. The protective effect exerted by defective virus particles does not appear related to interferon production in brain.", "contents": "Murine influenza virus encephalomyelitis. III. Effect of defective interfering virus particles. Defective interfering influenza virus particles lessened the yield of infective virus recovered from brain after intracerebral challange of 3-week old mice, but failed to affect the appearance of disease or lethality. In 7-week old mice, the presence of defective interfering influenza virus particles reduced both lethality and virus yield. Viral inocula containing significant numbers of defective particles appeared to diminish later inflammatory changes, nerve cell degeneration and the appearance of viral antigen in deeper cerebral regions. The protective effect exerted by defective virus particles does not appear related to interferon production in brain."} {"id": "PMID:1258611", "title": "The effects of measles virus and various strains of SSPE virus on organotypic cultures of nervous tissue.", "content": "The neurotropic effects, virologic behaviors and morphologic appearances of 4 strains of subacute sclerosing panencephalitis (SSPE) virus have been examined in organotypic cultures of hamster cerebellar tissue and have been compared with the Edmonston strain of measles virus in the same system. While measles virus caused extensive damage to nervous tissue, the SSPE strains, in general, exerted a less deleterious effect. All of the SSPE viruses replicated in this tissue. The SSPE strains showed morphologic variation ranging from normal measles-type virions to apparently nucleocapsid deficient forms. It is speculated that some of these differences between measles and SSPE virus may account for the differences in the in vivo conditions with which they are associated.", "contents": "The effects of measles virus and various strains of SSPE virus on organotypic cultures of nervous tissue. The neurotropic effects, virologic behaviors and morphologic appearances of 4 strains of subacute sclerosing panencephalitis (SSPE) virus have been examined in organotypic cultures of hamster cerebellar tissue and have been compared with the Edmonston strain of measles virus in the same system. While measles virus caused extensive damage to nervous tissue, the SSPE strains, in general, exerted a less deleterious effect. All of the SSPE viruses replicated in this tissue. The SSPE strains showed morphologic variation ranging from normal measles-type virions to apparently nucleocapsid deficient forms. It is speculated that some of these differences between measles and SSPE virus may account for the differences in the in vivo conditions with which they are associated."} {"id": "PMID:1258612", "title": "Neuro-Behcet's disease showing severe atrophy of the cerebrum.", "content": "A 38-year-old female died 6 years after the onset of what was, clinically and histopathologically, consistent with neuro-Behcet's disease. Pathologically the cerebrum showed severe atrophy. The main changes were observed in the grey and white matter, the diencephalon and the basal ganglia by light microscopy. All these changes originated in softenings around blood vessels, especially small vessels or capillaries. These foci fused together to form large regions of softening. Glial or mesenchymal reactions were minimal. In the white matter there was slight perivascular-infiltration, mainly consisting of lymphocytes. In view of these findings, it is suggested that these changes were caused by an allergic vasculitis. The present case of Neuro-Behcet's disease is the first one showing general atrophy of the cerebrum. It is very important in relation to demyelinating encephalitis.", "contents": "Neuro-Behcet's disease showing severe atrophy of the cerebrum. A 38-year-old female died 6 years after the onset of what was, clinically and histopathologically, consistent with neuro-Behcet's disease. Pathologically the cerebrum showed severe atrophy. The main changes were observed in the grey and white matter, the diencephalon and the basal ganglia by light microscopy. All these changes originated in softenings around blood vessels, especially small vessels or capillaries. These foci fused together to form large regions of softening. Glial or mesenchymal reactions were minimal. In the white matter there was slight perivascular-infiltration, mainly consisting of lymphocytes. In view of these findings, it is suggested that these changes were caused by an allergic vasculitis. The present case of Neuro-Behcet's disease is the first one showing general atrophy of the cerebrum. It is very important in relation to demyelinating encephalitis."} {"id": "PMID:1258613", "title": "Distribution of blood flow in myomatous uteri as measured by locally injected 133Xenon.", "content": "Regional blood flow in the myometrium and myomata has been measured during laparotomy in 11 patients using locally injected 133Xenon. Blood flow was calculated from the wash-out curves using both initial slope technique and compartment analysis. Assuming equal partition coefficients in myometrium and myomata the following values in ml-min-1-100 g-1 are seen: initial slope technique-myometrium 15.6 +/- 2.29, myomata 5.1 +/- 0.95, compartment analysis-myometrium 20.01 +/- 3.21, myomata 5.5 +/- 1.16. The blood flow was always lower in myomata than in myometrium of the same uterus. The main reason for the reduction of blood flow per unit weight of uterus in patients with myomata previously reported thus seems to be low blood flow in the myomata. A slight reduction of blood flow in the surrounding myometrium, however, also seems probable.", "contents": "Distribution of blood flow in myomatous uteri as measured by locally injected 133Xenon. Regional blood flow in the myometrium and myomata has been measured during laparotomy in 11 patients using locally injected 133Xenon. Blood flow was calculated from the wash-out curves using both initial slope technique and compartment analysis. Assuming equal partition coefficients in myometrium and myomata the following values in ml-min-1-100 g-1 are seen: initial slope technique-myometrium 15.6 +/- 2.29, myomata 5.1 +/- 0.95, compartment analysis-myometrium 20.01 +/- 3.21, myomata 5.5 +/- 1.16. The blood flow was always lower in myomata than in myometrium of the same uterus. The main reason for the reduction of blood flow per unit weight of uterus in patients with myomata previously reported thus seems to be low blood flow in the myomata. A slight reduction of blood flow in the surrounding myometrium, however, also seems probable."} {"id": "PMID:1258614", "title": "The intravenous infusion of prostaglandin F2alpha in the management of intrauterine death of the fetus.", "content": "Prostaglandin F2alpha (PGF2alpha) was given intravenously in the treatment of 16 cases of intrauterine death. Delivery was achieved without complications or side effects in 15 out of the 16 patients. A posterior cervical rupture occurred in one patient treated with cervical dilatation and PGF2alpha-infusion.", "contents": "The intravenous infusion of prostaglandin F2alpha in the management of intrauterine death of the fetus. Prostaglandin F2alpha (PGF2alpha) was given intravenously in the treatment of 16 cases of intrauterine death. Delivery was achieved without complications or side effects in 15 out of the 16 patients. A posterior cervical rupture occurred in one patient treated with cervical dilatation and PGF2alpha-infusion."} {"id": "PMID:1258615", "title": "A new technique for the localization of the cervix at 113mIn placental scintigraphy.", "content": "Sixty women in the third trimester of pregnancy were examined with 113mIn placental scintigraphy because of bleeding. In 24 of the cases, the scintigraphic procedure was initiated by application of a Meyers ring containing 113mIn round cervix. In the other cases, the fundus and the symphysis pubis were marked by means of a small radioactive source. Complete placenta praevia was correctly detected in 8 cases and marginal placenta in 4 cases. The scintigraphic localization of the placenta was correct in all the women where the ring was used, whereas when the external marked was used, seven errors occurred. The authors therefore recommend this new technique in order to facilitate the evaluation of the scintigrams.", "contents": "A new technique for the localization of the cervix at 113mIn placental scintigraphy. Sixty women in the third trimester of pregnancy were examined with 113mIn placental scintigraphy because of bleeding. In 24 of the cases, the scintigraphic procedure was initiated by application of a Meyers ring containing 113mIn round cervix. In the other cases, the fundus and the symphysis pubis were marked by means of a small radioactive source. Complete placenta praevia was correctly detected in 8 cases and marginal placenta in 4 cases. The scintigraphic localization of the placenta was correct in all the women where the ring was used, whereas when the external marked was used, seven errors occurred. The authors therefore recommend this new technique in order to facilitate the evaluation of the scintigrams."} {"id": "PMID:1258616", "title": "Influence of aging upon the urinary hormone excretion in the male.", "content": "The urinary excretion of LH, low polar oestrogens, neutral C19 and C21 steroids was measured in normal healthy males aged 20-79 years. No significant changes could be noted for the excretion of LH, pregnanediol and 17-ketogenic steroids between 50 and 79 years. The excretion of androsterone and aeticholanolone was significantly lower in the oldest group (70-79 years). A significant drop in the excretion of DHA was noted at approx. 60 years. The excretion of low polar oestrogens remained constant from 20 to 55-59 years, but showed a highly significant (P less than 0.001) decrease at about 60 years. This drop might reflect a sudden decrease in the plasma levels of oestrone sulphate due to a decreased sulphurylating activity in the liver.", "contents": "Influence of aging upon the urinary hormone excretion in the male. The urinary excretion of LH, low polar oestrogens, neutral C19 and C21 steroids was measured in normal healthy males aged 20-79 years. No significant changes could be noted for the excretion of LH, pregnanediol and 17-ketogenic steroids between 50 and 79 years. The excretion of androsterone and aeticholanolone was significantly lower in the oldest group (70-79 years). A significant drop in the excretion of DHA was noted at approx. 60 years. The excretion of low polar oestrogens remained constant from 20 to 55-59 years, but showed a highly significant (P less than 0.001) decrease at about 60 years. This drop might reflect a sudden decrease in the plasma levels of oestrone sulphate due to a decreased sulphurylating activity in the liver."} {"id": "PMID:1258617", "title": "Lumbar epidural analgesia in labour. A clinical analysis.", "content": "Lumbar epidural block was given for pain relief to 296 women in labour. Bupivacaine was used as the analgesic agent and the technique is described in detail. Satisfactory analgesia was obtained in 92% of the cases during the first stage of labour and in 84% during the second stage of labour. The frequency of instrumental deliveries and of occipitio-posterior position increased but the clinical condition of the newborn seemed to be unaffected.", "contents": "Lumbar epidural analgesia in labour. A clinical analysis. Lumbar epidural block was given for pain relief to 296 women in labour. Bupivacaine was used as the analgesic agent and the technique is described in detail. Satisfactory analgesia was obtained in 92% of the cases during the first stage of labour and in 84% during the second stage of labour. The frequency of instrumental deliveries and of occipitio-posterior position increased but the clinical condition of the newborn seemed to be unaffected."} {"id": "PMID:1258618", "title": "Fetal movements diagnosed by ultrasound in early pregnancy.", "content": "The purpose of this work was to ascertain whether ultrasonic techniques based on fetal movements were suitable for examinations in early pregnancy. The series consisted of 124 patients who came to be examined because of bleeding on the 6th-20th gestational week. The rapid B-scan method detected the fetal movements from the 8th week onwards, and the results were 100% reliable from the 10th week onwards. The combined A-B-scan method detected the fetal movements from the 12th week. Techniques based on the detection of fetal heart function were used as control methods. According to our results, the methods based on the indication of fetal movements constitute a practical alternative for elucidating the problems of early pregnancy.", "contents": "Fetal movements diagnosed by ultrasound in early pregnancy. The purpose of this work was to ascertain whether ultrasonic techniques based on fetal movements were suitable for examinations in early pregnancy. The series consisted of 124 patients who came to be examined because of bleeding on the 6th-20th gestational week. The rapid B-scan method detected the fetal movements from the 8th week onwards, and the results were 100% reliable from the 10th week onwards. The combined A-B-scan method detected the fetal movements from the 12th week. Techniques based on the detection of fetal heart function were used as control methods. According to our results, the methods based on the indication of fetal movements constitute a practical alternative for elucidating the problems of early pregnancy."} {"id": "PMID:1258619", "title": "Changes in the cervical blood flow during labour.", "content": "The cervical blood flow changes during labour in pregnant women (15 cases) have been studied by local injection of 133Xe into the cervix. The blood flow changes were compared with the external uterine pressure which was measured with a tocograph. During contractions the radioactivity decreased temporarily, but increased again between contractions. The overall decrease was greater in the control group (4 cases) than during spontaneous contractions. The conclusion is, that relative cervical blood circulation is rapidly changed during labour.", "contents": "Changes in the cervical blood flow during labour. The cervical blood flow changes during labour in pregnant women (15 cases) have been studied by local injection of 133Xe into the cervix. The blood flow changes were compared with the external uterine pressure which was measured with a tocograph. During contractions the radioactivity decreased temporarily, but increased again between contractions. The overall decrease was greater in the control group (4 cases) than during spontaneous contractions. The conclusion is, that relative cervical blood circulation is rapidly changed during labour."} {"id": "PMID:1258620", "title": "Unchanged total body calcium in normal human pregnancy.", "content": "The total body calcium--estimated from bone mineral content in the distal part of the forearm measured by use of photon absorptiometry--was determined during pregnancy in 13 women. The results indicate that total body calcium is constant during pregnancy.", "contents": "Unchanged total body calcium in normal human pregnancy. The total body calcium--estimated from bone mineral content in the distal part of the forearm measured by use of photon absorptiometry--was determined during pregnancy in 13 women. The results indicate that total body calcium is constant during pregnancy."} {"id": "PMID:1258621", "title": "Vaginal repair in the radical operation for cervical carcinoma.", "content": "An attempt was made to preserve postoperative sexual function and the recovery of bladder function by a simple modification of technique in 22 cases of radical operations for invasive carcinoma of the cervix. The procedures consisted of two parts. After removal of the specimen, the bladder peritoneal flap is sutured to the anterior vaginal wall leaving a 2 to 3 cm margin between the line of suture and the edge of the peritoneum. Similarly, the posterior peritoneal flap is sutured to posterior vaginal wall leaving a margin. Both edges of the peritoneum are then closed forming a pouch as an extension of vaginal canal. The length of the vagina was successfully elongated by this procedure, thus adding to better postoperative sexual function.", "contents": "Vaginal repair in the radical operation for cervical carcinoma. An attempt was made to preserve postoperative sexual function and the recovery of bladder function by a simple modification of technique in 22 cases of radical operations for invasive carcinoma of the cervix. The procedures consisted of two parts. After removal of the specimen, the bladder peritoneal flap is sutured to the anterior vaginal wall leaving a 2 to 3 cm margin between the line of suture and the edge of the peritoneum. Similarly, the posterior peritoneal flap is sutured to posterior vaginal wall leaving a margin. Both edges of the peritoneum are then closed forming a pouch as an extension of vaginal canal. The length of the vagina was successfully elongated by this procedure, thus adding to better postoperative sexual function."} {"id": "PMID:1258622", "title": "The effect of a copper IUD and various \"inert\" Iuds on the histological picture of the rabbit endometrium during early pseudopregnancy and pregnancy.", "content": "The influence of a copper IUD and two \"inert\" IUDs on the histological picture of the rabbit endometrium during early pseudopregnancy and early pregnancy was studied. The copper IUD markedly inhibited the endometrial maturation during the first five days of both pseudopregnancy and pregnancy. The \"inert\" IUDs had no such effect. The copper IUD prevented the normal response of the rabbit uterus to 17-beta-estradiol in castrated animals. The observed effects of the copper IUD might seriously interfere with the normal process of implantation.", "contents": "The effect of a copper IUD and various \"inert\" Iuds on the histological picture of the rabbit endometrium during early pseudopregnancy and pregnancy. The influence of a copper IUD and two \"inert\" IUDs on the histological picture of the rabbit endometrium during early pseudopregnancy and early pregnancy was studied. The copper IUD markedly inhibited the endometrial maturation during the first five days of both pseudopregnancy and pregnancy. The \"inert\" IUDs had no such effect. The copper IUD prevented the normal response of the rabbit uterus to 17-beta-estradiol in castrated animals. The observed effects of the copper IUD might seriously interfere with the normal process of implantation."} {"id": "PMID:1258623", "title": "Plasma renin activity in abortion.", "content": "Healthy women (N = 96) were investigated for changes in plasma renin activity (PRA) in abortion. In spontaneous abortion PRA levels were significantly lower than in induced abortion although higher than in healthy women. These findings may be explained by differences in corpus luteum function and renin production of the feto-placental unit. Alternatively, prostaglandins, released by the contracting uterus in spontaneous abortion may cause PRA suppression, as observed in 9 pregnant women with abortion induced by the intra-amniotic use of prostaglandin F2alpha.", "contents": "Plasma renin activity in abortion. Healthy women (N = 96) were investigated for changes in plasma renin activity (PRA) in abortion. In spontaneous abortion PRA levels were significantly lower than in induced abortion although higher than in healthy women. These findings may be explained by differences in corpus luteum function and renin production of the feto-placental unit. Alternatively, prostaglandins, released by the contracting uterus in spontaneous abortion may cause PRA suppression, as observed in 9 pregnant women with abortion induced by the intra-amniotic use of prostaglandin F2alpha."} {"id": "PMID:1258624", "title": "Congenital annular constrictions due to amniotic bands.", "content": "Amniotic bands which become involved with fetal parts, especially the extremities, are produced by rupture of the amnion during pregnancy with the consequent union of the extra-embryonic mesoderm in fibrous strings. An infant with the amniotic band syndrome, in whom an annular constriction of the left leg and right hand was found, is described. He was treated successfully by multiple Z-plasties and a plaster cast to correct the clubfoot. The oedema of the leg persisted for 5 weeks and then subsided completely. The role of amniotic abnormalities in the production of congenital malformations is reappraised. The microscopic and histological investigation of the placenta and membranes should accompany every case of fetal malformation in abortuses, stillbirths, and affected newborn.", "contents": "Congenital annular constrictions due to amniotic bands. Amniotic bands which become involved with fetal parts, especially the extremities, are produced by rupture of the amnion during pregnancy with the consequent union of the extra-embryonic mesoderm in fibrous strings. An infant with the amniotic band syndrome, in whom an annular constriction of the left leg and right hand was found, is described. He was treated successfully by multiple Z-plasties and a plaster cast to correct the clubfoot. The oedema of the leg persisted for 5 weeks and then subsided completely. The role of amniotic abnormalities in the production of congenital malformations is reappraised. The microscopic and histological investigation of the placenta and membranes should accompany every case of fetal malformation in abortuses, stillbirths, and affected newborn."} {"id": "PMID:1258625", "title": "Vaginal surgical intervention for a sacro-coccygeal teratoma obstructing labor.", "content": "Congenital sacro-coccygeal teratomas are rare tumors and may cause dystocia. The case presented was managed unusually by incisional drainage of the tumor through the vagina in a course of an obstructed labor, though the vaginal delivery resulted in the birth of a live, healthy infant.", "contents": "Vaginal surgical intervention for a sacro-coccygeal teratoma obstructing labor. Congenital sacro-coccygeal teratomas are rare tumors and may cause dystocia. The case presented was managed unusually by incisional drainage of the tumor through the vagina in a course of an obstructed labor, though the vaginal delivery resulted in the birth of a live, healthy infant."} {"id": "PMID:1258628", "title": "Haemophilia prophylaxis in Sweden.", "content": "29 boys (4-18 years old) with severe haemophilia A were given prophylactic infusions of AHF concentrate (human fraction I-0) for 2 to 13 years in an attempt to change the haemophilia from a severe to a moderate form and thereby prevent arthropathy and severe bleeding episodes. The sizes of the doses and the intervals at which the doses were given were titrated by AHF survival studies. As a rule, the patients received AHF in amounts sufficient to raise the AHF level to 30-45% at 5-12 day intervals. In about 50% of the infusions the AHF content was not below 1% before the next infusion. During such prophylaxis all patients except one have been in a good general condition. They have had bleeding episodes, which have, however, been much less severe and less frequent. The children have been able to live an almost normal life. The number and duration of stays in hospital have been markedly reduced. 17 of the patients had only minor or no joint defects before the start of the treatment. In this group the joint function was identical with that found in moderate haemophilia in the same age groups. Two patients developed anticoagulants. No other side effects were seen. The prophylactic regimen in Sweden thus reduced severe haemophilia to moderate.", "contents": "Haemophilia prophylaxis in Sweden. 29 boys (4-18 years old) with severe haemophilia A were given prophylactic infusions of AHF concentrate (human fraction I-0) for 2 to 13 years in an attempt to change the haemophilia from a severe to a moderate form and thereby prevent arthropathy and severe bleeding episodes. The sizes of the doses and the intervals at which the doses were given were titrated by AHF survival studies. As a rule, the patients received AHF in amounts sufficient to raise the AHF level to 30-45% at 5-12 day intervals. In about 50% of the infusions the AHF content was not below 1% before the next infusion. During such prophylaxis all patients except one have been in a good general condition. They have had bleeding episodes, which have, however, been much less severe and less frequent. The children have been able to live an almost normal life. The number and duration of stays in hospital have been markedly reduced. 17 of the patients had only minor or no joint defects before the start of the treatment. In this group the joint function was identical with that found in moderate haemophilia in the same age groups. Two patients developed anticoagulants. No other side effects were seen. The prophylactic regimen in Sweden thus reduced severe haemophilia to moderate."} {"id": "PMID:1258629", "title": "Influence of fat and carbohydrate content of diet on food intake and growth of male infants.", "content": "Two groups of normal fullterm infants were studied from 8 to 112 days of age while receiving formulas of the same caloric density and prepared from the same ingredients. A limited selection of strained foods were permitted. From the combination of formula and strained foods, one group received 29% of calories from fat and 62% from carbohydrate whereas the other received 57% from fat and 34% from carbohydrate. Fifteen infants in each group completed the study as planned. Energy intakes per kilogram and rates of gain in length and weight were similar in the two feeding groups.", "contents": "Influence of fat and carbohydrate content of diet on food intake and growth of male infants. Two groups of normal fullterm infants were studied from 8 to 112 days of age while receiving formulas of the same caloric density and prepared from the same ingredients. A limited selection of strained foods were permitted. From the combination of formula and strained foods, one group received 29% of calories from fat and 62% from carbohydrate whereas the other received 57% from fat and 34% from carbohydrate. Fifteen infants in each group completed the study as planned. Energy intakes per kilogram and rates of gain in length and weight were similar in the two feeding groups."} {"id": "PMID:1258630", "title": "Serum isoamylases in cystic fibrosis.", "content": "Salivary and pancreatic isoamylases were determined in the sera of 33 patients with cystic fibrosis (CF) and in 34 CF-parents. Pancreatic serum isoamylase activities were greatly decreased in patients with CF, and only two values from this group fell within the normal range. Salvary isoamylases, however, were markedly increased so that the total serum amylase activities were normal. We interpret the low pancreatic isoamylase levels in serum to reflect reduced exocrine masses in the pancreas of CF-children. In heterozygotes, the mean activity of the pancreatic isoamylase was significantly higher than in the reference group, while salivary isoamylases were within the normal range. Due to a genetic polymorphism pancreatic isoamylase may occur in two main fractions. This variant type of pancreatic isoamylase appeared more frequently in CF-heterozygotes than was expected from a reference group of blood donors.", "contents": "Serum isoamylases in cystic fibrosis. Salivary and pancreatic isoamylases were determined in the sera of 33 patients with cystic fibrosis (CF) and in 34 CF-parents. Pancreatic serum isoamylase activities were greatly decreased in patients with CF, and only two values from this group fell within the normal range. Salvary isoamylases, however, were markedly increased so that the total serum amylase activities were normal. We interpret the low pancreatic isoamylase levels in serum to reflect reduced exocrine masses in the pancreas of CF-children. In heterozygotes, the mean activity of the pancreatic isoamylase was significantly higher than in the reference group, while salivary isoamylases were within the normal range. Due to a genetic polymorphism pancreatic isoamylase may occur in two main fractions. This variant type of pancreatic isoamylase appeared more frequently in CF-heterozygotes than was expected from a reference group of blood donors."} {"id": "PMID:1258631", "title": "The Vater association: malformations of the male external genitalia.", "content": "Eight cases with the VATER association of malformations are presented. Maliformations of the external genitalia were found in 3 out of 7 male patients. Two of them presented with a bifid scrotum and a caudally displaced, dysplastic penis. Two patients had been exposed to progestin in early pregnancy and one of them had hyposadias and testicular atrophy. It is suggested that malformations of the male external genitalia might be part of malformations found in the VATER association.", "contents": "The Vater association: malformations of the male external genitalia. Eight cases with the VATER association of malformations are presented. Maliformations of the external genitalia were found in 3 out of 7 male patients. Two of them presented with a bifid scrotum and a caudally displaced, dysplastic penis. Two patients had been exposed to progestin in early pregnancy and one of them had hyposadias and testicular atrophy. It is suggested that malformations of the male external genitalia might be part of malformations found in the VATER association."} {"id": "PMID:1258632", "title": "Congenitally corrected transposition of the great arteries. A clinical study of 101 cases.", "content": "The anatomy, natural history, clinical features and symptomatology of 101 cases of congenitally corrected transposition of the great arteries (C-TGA) diagnosed over a 20-year period at Hospital for Sick Children, Toronto, Ontario, is reported. Only 1 patient had no association lesion and only 14 an intact ventricular septum. Pulmonary stenosis was present in a little more than half of the patients. Left A-V value involvement existed in 21 patients. In spite of the hich incidence of associated lesions with prognosis was better than expected. Seventy-six patients were alive at the end of the study, no one being critically ill. No death occurred among the patients with intact ventricular septum. Patients with pulmonary stenosis as a group developed symptoms later, were less handicapped and had a better prognosis than those without a pulmonary stenosis. One third of the patients had dysrhythmias. Eight patients having a 3rd degree AV-block. Auscultatory findings were not of too great a help when diagnosing C-TGA. Forty-seven patients had a single second sound, of these 37 had pulmonary stenosis. In 60% of the patients, where information was available, the second sound was reported to be of normal intensity. Our surgical experience is documented and discussed. Palliative procedures were done with successful results and low mortality. Totally corrective procedures were performed in 9 patients with 4 deaths.", "contents": "Congenitally corrected transposition of the great arteries. A clinical study of 101 cases. The anatomy, natural history, clinical features and symptomatology of 101 cases of congenitally corrected transposition of the great arteries (C-TGA) diagnosed over a 20-year period at Hospital for Sick Children, Toronto, Ontario, is reported. Only 1 patient had no association lesion and only 14 an intact ventricular septum. Pulmonary stenosis was present in a little more than half of the patients. Left A-V value involvement existed in 21 patients. In spite of the hich incidence of associated lesions with prognosis was better than expected. Seventy-six patients were alive at the end of the study, no one being critically ill. No death occurred among the patients with intact ventricular septum. Patients with pulmonary stenosis as a group developed symptoms later, were less handicapped and had a better prognosis than those without a pulmonary stenosis. One third of the patients had dysrhythmias. Eight patients having a 3rd degree AV-block. Auscultatory findings were not of too great a help when diagnosing C-TGA. Forty-seven patients had a single second sound, of these 37 had pulmonary stenosis. In 60% of the patients, where information was available, the second sound was reported to be of normal intensity. Our surgical experience is documented and discussed. Palliative procedures were done with successful results and low mortality. Totally corrective procedures were performed in 9 patients with 4 deaths."} {"id": "PMID:1258633", "title": "Measles vaccination. VIII. The occurrence of antibodies against virus envelope components after immunization with inactivated vaccine. Effects of revaccination with live measles vaccine.", "content": "Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8-9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-inhibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable in their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to faccination. 4 vaccinees with low pre-vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by sue of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin.", "contents": "Measles vaccination. VIII. The occurrence of antibodies against virus envelope components after immunization with inactivated vaccine. Effects of revaccination with live measles vaccine. Children immunized with 4 doses of formalin-inactivated vaccine and/or purified hemagglutinin prepared from Tween 80-ether (TE) treated material were subjected to a follow-up 8-9 years after the last dose of vaccine. 11 out of 27 children had clinical and/or serological signs of infections with wild measles virus during the 8 to 9 years post-booster period. 10 out of the 11 children with infections had non-hemagglutinating-inhibiting (HI) hemolysis-inhibiting (HLI) antibodies demonstrable in their sera after removal of HI antibodies by absorption with TE antigen. In contrast 13 out of 16 vaccinees without detectable signs of infection lacked non-HI HLI antibodies. 10 out of these 13 children were vaccinated with further attenuated live measles virus. There were no clinical reactions to faccination. 4 vaccinees with low pre-vaccination HI antibody titers showed significant rises of antibody titers including non-HI HLI antibodies. In the remaining children no take of the live vaccine could be demonstrated. Thus HI antibodies of a certain minimal concentration can block the replication of vaccine virus even in the absence of non-HI HLI antibodies. However, since it will be difficult to establish these conditions by sue of available inactivated vaccines it is recommended that future vaccine products should include both major virus envelope surface components, the hemagglutinin and the hemolysin."} {"id": "PMID:1258634", "title": "Evaluation of single oral dose metyrapone tests in children with hypopituitarism.", "content": "Evaluation of single-dose metyrapone tests in children with hypopituitarism; comparison with the prolonged metyrapone and insulin induced hypoglycaemia tests and their relationship with the etiology of hypopituitarism. Acta Paediatr Scand, 65:177, 1976.--Pituitary-adrenal reserve was evaluated in control and hypopituitary subjects by comparing the 8 a.m. plasma 11-deoxycorticoid response (11-DOCS) to a single midnight oral dose of metyrapone (short test) with 1) the 8 a.m. 11-DOCS increase under repeated oral doses of metyrapone (prolonged test) and 2) with the plasma corticoid response during arginine-insulin test. In the short and the prolonged metyrapone tests, the same response was obtained in 25 out of 27 patients. The short test was repeated in 22 patients and the 11-DOCS response did not show a significant difference. In 34 of 40 patients, the response to the short test was comparable to the response during the arginine-insulin test; only 3 patients with a normal 11-DOCS rise to the short test had a low response to insulin and vice versa. Among the low responders to the short test, the mean 11-DOCS value was significantly lower in subjects with operated craniopharyngiomas than in idiopathic hypopituitary patients (p less than 0.001). In the short test, the 8 a.m. baseline cortisol value was positively correlated with the 8 a.m. 11-DOCS response (p less than 0.001), the cortisol level allowing to predict the 11-DOCS response in 28 out of 53 patients. Thus, the short oral metyrapone stimulation was found to be a reliable test in hypopituitary children.", "contents": "Evaluation of single oral dose metyrapone tests in children with hypopituitarism. Evaluation of single-dose metyrapone tests in children with hypopituitarism; comparison with the prolonged metyrapone and insulin induced hypoglycaemia tests and their relationship with the etiology of hypopituitarism. Acta Paediatr Scand, 65:177, 1976.--Pituitary-adrenal reserve was evaluated in control and hypopituitary subjects by comparing the 8 a.m. plasma 11-deoxycorticoid response (11-DOCS) to a single midnight oral dose of metyrapone (short test) with 1) the 8 a.m. 11-DOCS increase under repeated oral doses of metyrapone (prolonged test) and 2) with the plasma corticoid response during arginine-insulin test. In the short and the prolonged metyrapone tests, the same response was obtained in 25 out of 27 patients. The short test was repeated in 22 patients and the 11-DOCS response did not show a significant difference. In 34 of 40 patients, the response to the short test was comparable to the response during the arginine-insulin test; only 3 patients with a normal 11-DOCS rise to the short test had a low response to insulin and vice versa. Among the low responders to the short test, the mean 11-DOCS value was significantly lower in subjects with operated craniopharyngiomas than in idiopathic hypopituitary patients (p less than 0.001). In the short test, the 8 a.m. baseline cortisol value was positively correlated with the 8 a.m. 11-DOCS response (p less than 0.001), the cortisol level allowing to predict the 11-DOCS response in 28 out of 53 patients. Thus, the short oral metyrapone stimulation was found to be a reliable test in hypopituitary children."} {"id": "PMID:1258635", "title": "Hypohistidinemia in juvenile rheumatoid arthritis.", "content": "The mean level of plasma histidine in 86 children with rheumatoid arthritis was found to be significantly lower in comparison with that of controls. The possible influence of various drugs on the plasma histidine concentration is discussed.", "contents": "Hypohistidinemia in juvenile rheumatoid arthritis. The mean level of plasma histidine in 86 children with rheumatoid arthritis was found to be significantly lower in comparison with that of controls. The possible influence of various drugs on the plasma histidine concentration is discussed."} {"id": "PMID:1258636", "title": "Health screening of four-year-olds in a Swedish county. III. Variation of effectiveness among examining teams.", "content": "The data gathered in connection with a routine health screening program for 4-year-olds were used in order to test a number of hypotheses concerning factors which might have influenced the effectiveness of the program, as well as concerning the quality of preventive care delivered to the children before the age of 4 years. It was found that preventive care of relatively high quality delivered to children 0-3 years of age had not reduced the prevalence of previously undetected health problems at 4 years of age. Furthermore, the analysis demonstrated substantial differences between physicians in the rates of correct and unnecessary referrals. Only a small part of these differences could be attributed to professional status or specific experience with the program. They consisted essentially in varying thresholds for what was perceived as a health problem needing treatment, and were considered as a matter of personal temperament. True differences of quality did occur but were less prominent. The implications of these findings with regard to the continuation of the program are discussed.", "contents": "Health screening of four-year-olds in a Swedish county. III. Variation of effectiveness among examining teams. The data gathered in connection with a routine health screening program for 4-year-olds were used in order to test a number of hypotheses concerning factors which might have influenced the effectiveness of the program, as well as concerning the quality of preventive care delivered to the children before the age of 4 years. It was found that preventive care of relatively high quality delivered to children 0-3 years of age had not reduced the prevalence of previously undetected health problems at 4 years of age. Furthermore, the analysis demonstrated substantial differences between physicians in the rates of correct and unnecessary referrals. Only a small part of these differences could be attributed to professional status or specific experience with the program. They consisted essentially in varying thresholds for what was perceived as a health problem needing treatment, and were considered as a matter of personal temperament. True differences of quality did occur but were less prominent. The implications of these findings with regard to the continuation of the program are discussed."} {"id": "PMID:1258637", "title": "Cerebellar-ataxic syndrome in children and adolescents with hypothyroidism under treatment.", "content": "Animal experiments and observations on quantitative growth of human cerebellum suggest a critical period when its development is particularly vulnerable to hypothyroidism. Sixty-seven patients aged 7-24 years with hypothyroidism under long-term treatment were examined for ataxic symptoms. These were found in 24 of 39 patients (60%) hypothyroid before or during the third month of life. Only 4 of 18 patients (20%) hypothyroid later had cerebellar symptoms. Such symptoms could be evidence for the onset of hypothyroidism before or during the 3rd month of life. Seventeen (80%) of mentally retarded patients had cerebellar symptoms compared with 11 (30%) of 45 attending normal school. Even retrospectively, these data might permit a more accurate prognosis of further mental development in hypothyroid children.", "contents": "Cerebellar-ataxic syndrome in children and adolescents with hypothyroidism under treatment. Animal experiments and observations on quantitative growth of human cerebellum suggest a critical period when its development is particularly vulnerable to hypothyroidism. Sixty-seven patients aged 7-24 years with hypothyroidism under long-term treatment were examined for ataxic symptoms. These were found in 24 of 39 patients (60%) hypothyroid before or during the third month of life. Only 4 of 18 patients (20%) hypothyroid later had cerebellar symptoms. Such symptoms could be evidence for the onset of hypothyroidism before or during the 3rd month of life. Seventeen (80%) of mentally retarded patients had cerebellar symptoms compared with 11 (30%) of 45 attending normal school. Even retrospectively, these data might permit a more accurate prognosis of further mental development in hypothyroid children."} {"id": "PMID:1258638", "title": "A case of impaired chemotaxis and lymphocyte transformation.", "content": "The report describes the clinical syndroms of a 14-year-old boy which suffered from recurrent infections since early infancy. The clinical and general laboratory findings were similar to \"the granulomatous disease of childhood\" as described by Bridges et al. (8). The following serum factors were determined: Immunoglobulins, complement factors, isoagglutinins. The following assays with normal or patient's granulocytes were done: Chemotactic activity, nitroblue-tetrazolium test, bactericidal assay, fungicidal assay, myeloperoxidase, monocytes fungicidal assay. Immunological studies include kinetics of phytohaemagglutinin response, effect of serum of the patient on lymphocytic reactivity in vitro and skin tests. The following results were obtained: 1) Assays with normal or patient's granulocytes showed an impaired chemotatic activity, when serum of the patient was added. There was strong indication by treatment of the patient with plasma infusions, that the chemotactic defect is a serum dependent factor. 2) It could be demonstrated that the patient's serum also inhibited the response of lymphocytes to tuberculin and phytohaemagglutinin. Therefore the patient report focuses attention upon the possibility of serum related abnormalities that may influence granulocytic as well as lymphocytic functions leading to recurrent bacterial, fungal and viral infections.", "contents": "A case of impaired chemotaxis and lymphocyte transformation. The report describes the clinical syndroms of a 14-year-old boy which suffered from recurrent infections since early infancy. The clinical and general laboratory findings were similar to \"the granulomatous disease of childhood\" as described by Bridges et al. (8). The following serum factors were determined: Immunoglobulins, complement factors, isoagglutinins. The following assays with normal or patient's granulocytes were done: Chemotactic activity, nitroblue-tetrazolium test, bactericidal assay, fungicidal assay, myeloperoxidase, monocytes fungicidal assay. Immunological studies include kinetics of phytohaemagglutinin response, effect of serum of the patient on lymphocytic reactivity in vitro and skin tests. The following results were obtained: 1) Assays with normal or patient's granulocytes showed an impaired chemotatic activity, when serum of the patient was added. There was strong indication by treatment of the patient with plasma infusions, that the chemotactic defect is a serum dependent factor. 2) It could be demonstrated that the patient's serum also inhibited the response of lymphocytes to tuberculin and phytohaemagglutinin. Therefore the patient report focuses attention upon the possibility of serum related abnormalities that may influence granulocytic as well as lymphocytic functions leading to recurrent bacterial, fungal and viral infections."} {"id": "PMID:1258639", "title": "Massive chronic feto-maternal bleeding associated with placental chorioangiomas.", "content": "After pregnancy complicated by polyhydramnios and the antenatal discovery of a very large placenta a newborn infant suffered from anemia, thrombocytopenia and hypoproteinemic edema, and was successfully treated by exchange transfusion. The placenta contained two chorioangiomas and there was diffuse placental hypertrophy with edema and patchy chorioangiomatosis. There was evidence of major chronic feto-maternal bleeding which could be the explanation for most of the hematological and biochemical problems which occurred. The child was developing normally at subsequent follow-up aged 15 weeks.", "contents": "Massive chronic feto-maternal bleeding associated with placental chorioangiomas. After pregnancy complicated by polyhydramnios and the antenatal discovery of a very large placenta a newborn infant suffered from anemia, thrombocytopenia and hypoproteinemic edema, and was successfully treated by exchange transfusion. The placenta contained two chorioangiomas and there was diffuse placental hypertrophy with edema and patchy chorioangiomatosis. There was evidence of major chronic feto-maternal bleeding which could be the explanation for most of the hematological and biochemical problems which occurred. The child was developing normally at subsequent follow-up aged 15 weeks."} {"id": "PMID:1258640", "title": "Acid activation of renin in rabbit uterus.", "content": "During the first 2 days post-partum there is a rapid fall in the uterine renin content of the rabbit. A similar loss of renin can be reproduced in vitro when pregnant and post-partum and to a lesser degree non-pregnant uterine tissue slices are incubated at pH 7.4 at 37 degrees C. When a secondary incubation of these previously incubated preparations is performed at pH 4.8 an activation of renin is seen. There was not an inverse correlation between the amounts of renin lost during the primary incubation at pH 7.4 and the amounts of renin activated during the secondary incubation at pH 4.8. In similarly incubated preparations of kidney cortex, where only a small per cent of the initial renin content is lost during the primary incubation at pH 7.4, no activatable renin is seen.", "contents": "Acid activation of renin in rabbit uterus. During the first 2 days post-partum there is a rapid fall in the uterine renin content of the rabbit. A similar loss of renin can be reproduced in vitro when pregnant and post-partum and to a lesser degree non-pregnant uterine tissue slices are incubated at pH 7.4 at 37 degrees C. When a secondary incubation of these previously incubated preparations is performed at pH 4.8 an activation of renin is seen. There was not an inverse correlation between the amounts of renin lost during the primary incubation at pH 7.4 and the amounts of renin activated during the secondary incubation at pH 4.8. In similarly incubated preparations of kidney cortex, where only a small per cent of the initial renin content is lost during the primary incubation at pH 7.4, no activatable renin is seen."} {"id": "PMID:1258641", "title": "The extent of carcinoma in situ in urinary bladders with primary carcinomas.", "content": "The occurrence of carcinoma in situ was examined in a consequtive series of cystectomy specimens from 43 patients. All patients were suffering from or had been suffering from primary bladder cancer. Carcinoma in situ was defined as a definitive polymorphia of enlarged nuclei with abnormal chromatin structure in non-tumour bearing areas. It was found in 26 bladders. By means of a systematic technique of cutting the specimens, the extent of the alterations was quantitied, relating the number of blocks containing the alteration to the total number of blocks in which the changes possibly might be present. The extent of carcinoma in situ ranged from 2 to 81% with an average of 20%. The distribution of the alterations was unpredictable, often strongly focal, most often in continuation of the tumour. In one specimen, the margins of resection were involved. The extent was largest in bladders with poorly differentiated tumours. A temporal relationship between in situ carcinoma and invasive carcinoma could not be shown, as regards tumour size and duration of clinical symptoms. The morphology of the changes is discussed seen in the light of variations in the normal epithelium lining the lower urinary tract. Minor degrees of atypia of the epithelium showed rather bad reproduction. The dominating occurrence of carcinoma in situ in bladders with poorly differentiated tumours may either be a manifestation of a biological difference between tumours of different grades of differentiation or that the morphological criteria used correspond to the in situ type of poorly differentiated tumours.", "contents": "The extent of carcinoma in situ in urinary bladders with primary carcinomas. The occurrence of carcinoma in situ was examined in a consequtive series of cystectomy specimens from 43 patients. All patients were suffering from or had been suffering from primary bladder cancer. Carcinoma in situ was defined as a definitive polymorphia of enlarged nuclei with abnormal chromatin structure in non-tumour bearing areas. It was found in 26 bladders. By means of a systematic technique of cutting the specimens, the extent of the alterations was quantitied, relating the number of blocks containing the alteration to the total number of blocks in which the changes possibly might be present. The extent of carcinoma in situ ranged from 2 to 81% with an average of 20%. The distribution of the alterations was unpredictable, often strongly focal, most often in continuation of the tumour. In one specimen, the margins of resection were involved. The extent was largest in bladders with poorly differentiated tumours. A temporal relationship between in situ carcinoma and invasive carcinoma could not be shown, as regards tumour size and duration of clinical symptoms. The morphology of the changes is discussed seen in the light of variations in the normal epithelium lining the lower urinary tract. Minor degrees of atypia of the epithelium showed rather bad reproduction. The dominating occurrence of carcinoma in situ in bladders with poorly differentiated tumours may either be a manifestation of a biological difference between tumours of different grades of differentiation or that the morphological criteria used correspond to the in situ type of poorly differentiated tumours."} {"id": "PMID:1258642", "title": "Types of metaplasia in forty urothelial bladder carcinomas. A systematic histological investigation.", "content": "In a systematic study of bladders from consecutively cystectomized patients, 40 primary urinary bladder carcinomas were examined with regard to the type of differentiation. Metaplastic areas were found in 24 of the tumours. A positive reaction of keratin to Kreybergs stain was required for the definition squamous metaplasia. Squamous areas were found in 16 of the tumours. In 4 tumours there was, in addition to squamos metaplasia, glandular metaplasia which was defined as definite glandular tissue with dysplasia of the epithelium. In 4 tumours, glandular metaplasia was also present in addition to the urothelial carcinoma. In 18 cases, metaplastic changes were present in the luminal portion of the tumour from which the biopsy material and desquaminated material originated. The occurrence of metaplasia was related to the degree of differentiation of the urothelial part of the tumour. Metaplastic changes were most frequent in the poorly differentiated tumours. The biopsies obtained pre-operatively permitted of the diagnosis metaplasia being made in 15 cases, while the cytological material suggested metaplastic changes in 4 cases only. The biological function of metaplasia is unknow. The possibility that these areas will react differently to radiation and chemotherapy is present and the frequency of such changes would suggest that their importance should be studied by their registration as mixed forms as stated by WHO.", "contents": "Types of metaplasia in forty urothelial bladder carcinomas. A systematic histological investigation. In a systematic study of bladders from consecutively cystectomized patients, 40 primary urinary bladder carcinomas were examined with regard to the type of differentiation. Metaplastic areas were found in 24 of the tumours. A positive reaction of keratin to Kreybergs stain was required for the definition squamous metaplasia. Squamous areas were found in 16 of the tumours. In 4 tumours there was, in addition to squamos metaplasia, glandular metaplasia which was defined as definite glandular tissue with dysplasia of the epithelium. In 4 tumours, glandular metaplasia was also present in addition to the urothelial carcinoma. In 18 cases, metaplastic changes were present in the luminal portion of the tumour from which the biopsy material and desquaminated material originated. The occurrence of metaplasia was related to the degree of differentiation of the urothelial part of the tumour. Metaplastic changes were most frequent in the poorly differentiated tumours. The biopsies obtained pre-operatively permitted of the diagnosis metaplasia being made in 15 cases, while the cytological material suggested metaplastic changes in 4 cases only. The biological function of metaplasia is unknow. The possibility that these areas will react differently to radiation and chemotherapy is present and the frequency of such changes would suggest that their importance should be studied by their registration as mixed forms as stated by WHO."} {"id": "PMID:1258643", "title": "Correlation of enzyme histochemical and structural segmentation in the proximal convoluted tubule of the rat kidney. Enzyme activity compared to the freeze-dried structure of serial-sectioned normal rat nephrons.", "content": "In the normal rat kidney enzyme histochemical activity was correlated with the structural segmentation of the convoluted part of the proximal tubule, as seen in freeze-dried sections. Serial sections were employed for alternate morphological and enzyme histochemical studies. The tubules were investigated for activity of the following enzymes: 1) non-specific acid phosphatases, 2) non-specific alkaline phosphatases, 3) succinate dehydrogenase and 4) non-specific esterases. Close to the urinary pole acid phosphatase activity was slight in all instances, whilst in the first and second segment a gradual increase in tubular cells with heavy enzyme activity was seen. All tubular cells at the urinary pole showed heavy alkaline phosphatase activity, but there was a gradual increase of cells showing slight enzyme activity in the first and second segments. Succinate dehydrogenase activity was constantly heavy at the urinary pole, and there was a gradual decrease in these cells with heavy enzyme activity along the course of the first and second segments. The pattern of tubular enzyme activity for these three enzymes was independent of the nephron level in the renal cortex. The non-specific esterase activity was, in comparison, uniform throughout the length of the proximal tubule in nephrons from all levels of the renal cortex. This combined enzyme histochemical and morphological investigation demonstrates conclusively that there is a close correlation between structural segmentation and the pattern of enzyme activity of non-specific acid and alkaline phosphatases and succinate dehydrogenase in the proximal convoluted tubule of normal rat kidney.", "contents": "Correlation of enzyme histochemical and structural segmentation in the proximal convoluted tubule of the rat kidney. Enzyme activity compared to the freeze-dried structure of serial-sectioned normal rat nephrons. In the normal rat kidney enzyme histochemical activity was correlated with the structural segmentation of the convoluted part of the proximal tubule, as seen in freeze-dried sections. Serial sections were employed for alternate morphological and enzyme histochemical studies. The tubules were investigated for activity of the following enzymes: 1) non-specific acid phosphatases, 2) non-specific alkaline phosphatases, 3) succinate dehydrogenase and 4) non-specific esterases. Close to the urinary pole acid phosphatase activity was slight in all instances, whilst in the first and second segment a gradual increase in tubular cells with heavy enzyme activity was seen. All tubular cells at the urinary pole showed heavy alkaline phosphatase activity, but there was a gradual increase of cells showing slight enzyme activity in the first and second segments. Succinate dehydrogenase activity was constantly heavy at the urinary pole, and there was a gradual decrease in these cells with heavy enzyme activity along the course of the first and second segments. The pattern of tubular enzyme activity for these three enzymes was independent of the nephron level in the renal cortex. The non-specific esterase activity was, in comparison, uniform throughout the length of the proximal tubule in nephrons from all levels of the renal cortex. This combined enzyme histochemical and morphological investigation demonstrates conclusively that there is a close correlation between structural segmentation and the pattern of enzyme activity of non-specific acid and alkaline phosphatases and succinate dehydrogenase in the proximal convoluted tubule of normal rat kidney."} {"id": "PMID:1258644", "title": "Atypical fibroxanthoma of the skin. A clinico-pathological study of 57 cases.", "content": "A retrospective study of 57 patients with atypical fibroxanthoma of the skin is presented. The light microscopy is described and the differential diagnosis is discussed. Most of the atypical fibroxanthomas (32 out of 57 cases) were originally diagnosed as soft tissue sarcomas, e.g. fibrosarcoma, dermatofibrosarcoma, neurofibrosarcoma, myosarcoma and unspecified sarcoma. The tumour occurred chiefly in middle-aged and elderly patients; three patients were 15 years old or younger. The median age was 73 years in patients in whom the tumour occurred in the head and neck, and 34 years in patients in whom the tumour developed on the extremities and trunk. The sex ratio (male to female) was almost equal. Follow-up information about 43 patients was available. The follow-up period ranged from 1 year to 25 years with a median of 9 years. Eight patients died from intercurrent disease; all the other 35 patients are alive and well. The clinical course was benign in all but one patient in whom a recurrence developed and metastases to the regional lymph nodes appeared 7 years after the initial excision. The tumour in this case did not differ histologically from the other atypical fibroxanthomas with respect to cellularity, cellular and nuclear atypia or mitotic activity. It is suggested that the recurrence per se might be of prognostic importance.", "contents": "Atypical fibroxanthoma of the skin. A clinico-pathological study of 57 cases. A retrospective study of 57 patients with atypical fibroxanthoma of the skin is presented. The light microscopy is described and the differential diagnosis is discussed. Most of the atypical fibroxanthomas (32 out of 57 cases) were originally diagnosed as soft tissue sarcomas, e.g. fibrosarcoma, dermatofibrosarcoma, neurofibrosarcoma, myosarcoma and unspecified sarcoma. The tumour occurred chiefly in middle-aged and elderly patients; three patients were 15 years old or younger. The median age was 73 years in patients in whom the tumour occurred in the head and neck, and 34 years in patients in whom the tumour developed on the extremities and trunk. The sex ratio (male to female) was almost equal. Follow-up information about 43 patients was available. The follow-up period ranged from 1 year to 25 years with a median of 9 years. Eight patients died from intercurrent disease; all the other 35 patients are alive and well. The clinical course was benign in all but one patient in whom a recurrence developed and metastases to the regional lymph nodes appeared 7 years after the initial excision. The tumour in this case did not differ histologically from the other atypical fibroxanthomas with respect to cellularity, cellular and nuclear atypia or mitotic activity. It is suggested that the recurrence per se might be of prognostic importance."} {"id": "PMID:1258645", "title": "Cytoplasmic effects of x-irradiation on cultured cells in a nondividing stage. 1. Establishment of an experimental model.", "content": "The investigation was initiated with the aim of establishing a suitable experimental model with respect to mode of radiation and radiation dose for elucidating morphologically the sequential development of radiation induced damage of interphase cells (human glia cells in vitro). Adequately defined and reproducible cellular changes were obtained using X-radiation generated by an 8 MeV linear accelerator at a dose of 20,000 rad. The cellular alterations were studied in the light microscope and by scanning and transmission electron microscopy. The most conspicuous changes--first appreciable about 5 hours after irradiation--occurred in the lysosomal vacuome, and the plasma membrane and associated structures.", "contents": "Cytoplasmic effects of x-irradiation on cultured cells in a nondividing stage. 1. Establishment of an experimental model. The investigation was initiated with the aim of establishing a suitable experimental model with respect to mode of radiation and radiation dose for elucidating morphologically the sequential development of radiation induced damage of interphase cells (human glia cells in vitro). Adequately defined and reproducible cellular changes were obtained using X-radiation generated by an 8 MeV linear accelerator at a dose of 20,000 rad. The cellular alterations were studied in the light microscope and by scanning and transmission electron microscopy. The most conspicuous changes--first appreciable about 5 hours after irradiation--occurred in the lysosomal vacuome, and the plasma membrane and associated structures."} {"id": "PMID:1258646", "title": "Experimental avian nephropathy. Changes of renal function and structure induced by ochratoxin A-contaminated feed.", "content": "One-day-old chickens were fed ochratoxin A-contaminated diets at 2 levels: 0.3 and 1 mg ochratoxin A per kg feed, for 341 days. The only observable lesion to develop was a kidney damage comparable with the naturally occurring avian nephropathy. The changes in renal function were characterized by impairment of glomerular and tubular function, indicated by a decreased inulin clearance, TmPAH and decreased urine concentrating capacity. The changes of renal structure included degeneration of the tubular epithelium accompanied by regeneration. At slaughter, the kidneys, liver and muscular tissue of the birds contained residues of ochratoxin A (up to 50 mug per kg). As all the birds would have passed the meat inspection because no macroscopical lesions were present, this represents a possible health problem.", "contents": "Experimental avian nephropathy. Changes of renal function and structure induced by ochratoxin A-contaminated feed. One-day-old chickens were fed ochratoxin A-contaminated diets at 2 levels: 0.3 and 1 mg ochratoxin A per kg feed, for 341 days. The only observable lesion to develop was a kidney damage comparable with the naturally occurring avian nephropathy. The changes in renal function were characterized by impairment of glomerular and tubular function, indicated by a decreased inulin clearance, TmPAH and decreased urine concentrating capacity. The changes of renal structure included degeneration of the tubular epithelium accompanied by regeneration. At slaughter, the kidneys, liver and muscular tissue of the birds contained residues of ochratoxin A (up to 50 mug per kg). As all the birds would have passed the meat inspection because no macroscopical lesions were present, this represents a possible health problem."} {"id": "PMID:1258647", "title": "Sex differences in renal damage induced in the rat by the Finnish mushroom, Cortinarius speciosissimus.", "content": "The sensitivity of male and female rats to Cortinarius speciosissimus toxins was compared. Dried, homogenized mushroom was given orally by stomach tubing at a dose of 250 mg dried mushroom/kg body weight. Both in males and in females, the kidneys were the only organs showing macroscopical changes. Sex differences in renal damage were observed in the area of the inner cortex.", "contents": "Sex differences in renal damage induced in the rat by the Finnish mushroom, Cortinarius speciosissimus. The sensitivity of male and female rats to Cortinarius speciosissimus toxins was compared. Dried, homogenized mushroom was given orally by stomach tubing at a dose of 250 mg dried mushroom/kg body weight. Both in males and in females, the kidneys were the only organs showing macroscopical changes. Sex differences in renal damage were observed in the area of the inner cortex."} {"id": "PMID:1258667", "title": "Formation and action of prostaglandin endoperoxides in the isolated human umbilical artery.", "content": "The effects on the isolated human umbilical artery (HUA) of the recently isolated endoperoxide intermediates in prostaglandin (PG) biosynthesis, PGG2 and PGH2, were studied. Both endoperoxides were potent contractors of the artery strips, the threshold concentrations being 3 (1-4) ng/ml for PGG2 and 1 (1-12) ng/ml for PGH2, as compared with 200 (40-400) ng/ml for PGE2. The hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (thromboxane B2), a metabolite of PGG2, appeared in the bath medium indicating PG and thromboxane generation in the isolated HUA. The formation of thromboxane B2 was inhibited by indomethacin (8-40 mug/ml) and by eicosa-5,8,11,14-tetraynoic acid (ETA) (25 mug/ml), ETA also inhibited the contractile responses to both endoperoxides. The results support the view that local generation of PGs might be involved in the closure of the HUA at birth.", "contents": "Formation and action of prostaglandin endoperoxides in the isolated human umbilical artery. The effects on the isolated human umbilical artery (HUA) of the recently isolated endoperoxide intermediates in prostaglandin (PG) biosynthesis, PGG2 and PGH2, were studied. Both endoperoxides were potent contractors of the artery strips, the threshold concentrations being 3 (1-4) ng/ml for PGG2 and 1 (1-12) ng/ml for PGH2, as compared with 200 (40-400) ng/ml for PGE2. The hemiacetal derivative of 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (thromboxane B2), a metabolite of PGG2, appeared in the bath medium indicating PG and thromboxane generation in the isolated HUA. The formation of thromboxane B2 was inhibited by indomethacin (8-40 mug/ml) and by eicosa-5,8,11,14-tetraynoic acid (ETA) (25 mug/ml), ETA also inhibited the contractile responses to both endoperoxides. The results support the view that local generation of PGs might be involved in the closure of the HUA at birth."} {"id": "PMID:1258668", "title": "A method for preparing isolated glands from the rabbit gastric mucosa.", "content": "A method for isolating gastric glands from the corpus of the rabbit gastric mucosa is presented. The stomach of an anesthetized rabbit was perfused with saline under high pressure through the aorta, taken out and emptied. The mucosa was stripped off, minced into small pieces and transferred to a 1 mg/ml collagenase solution. After 90 min at 37 degrees C, a large number of isolated gastric glands and cells were separated free. By a simple washing procedure the glands were freed from cell contamination and collagenase. The gastric glands were viable, as demonstrated by dye exclusion technique, oxygen consumption and electrolyte content. For identification of the glandular cells both common staining techniques and electron microscopy were used. Four types of cells were identified, viz. parietal cells, zymogen cells, mucous neck cells and some endocrine cells. The intracellular morphology of the glandular cells did not differ significantly from that seen in intact gastric mucosa. The glands could be stimulated with histamine, in a dose-response manner, as revealed by the increase in oxygen consumption (ED-50 equal 3 X 10(-6) M). This isolated gastric gland preparation may serve as a useful tool for new approaches in gastric physiology.", "contents": "A method for preparing isolated glands from the rabbit gastric mucosa. A method for isolating gastric glands from the corpus of the rabbit gastric mucosa is presented. The stomach of an anesthetized rabbit was perfused with saline under high pressure through the aorta, taken out and emptied. The mucosa was stripped off, minced into small pieces and transferred to a 1 mg/ml collagenase solution. After 90 min at 37 degrees C, a large number of isolated gastric glands and cells were separated free. By a simple washing procedure the glands were freed from cell contamination and collagenase. The gastric glands were viable, as demonstrated by dye exclusion technique, oxygen consumption and electrolyte content. For identification of the glandular cells both common staining techniques and electron microscopy were used. Four types of cells were identified, viz. parietal cells, zymogen cells, mucous neck cells and some endocrine cells. The intracellular morphology of the glandular cells did not differ significantly from that seen in intact gastric mucosa. The glands could be stimulated with histamine, in a dose-response manner, as revealed by the increase in oxygen consumption (ED-50 equal 3 X 10(-6) M). This isolated gastric gland preparation may serve as a useful tool for new approaches in gastric physiology."} {"id": "PMID:1258669", "title": "Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. I. Disynaptic Ia inhibition of Ia inhibitory interneurones.", "content": "Interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as \"Ia inhibitory interneurones\") were recorded in the lumbar spinal cord of the cat. It was revealed that the Ia inhibitory interneurones themselves receive disynaptic Ia inhibition. The muscles from which this inhibition is evoked are strictly antagonistic to those supplying their Ia excitation. Similar to the Ia inhibition in motoneurones the Ia inhibition in the Ia inhibitory interneurones is decreased when preceded by an antidromic stimulation of ventral roots. Furthermore, transmission of Ia inhibition to the Ia inhibitory interneurones is facilitated from ipsilateral and contralateral primary afferents as well as several supraspinal pathways analogous to earlier findings for the Ia inhibition of motoneurones. The pattern and control of the Ia inhibition of motoneurones and of Ia inhibitory interneurones display so striking similarities that it is suggested that identical interneurones are responsible. The conclusion thus emerges that \"opposite\" Ia inhibitory interneurones (i.e. interneurones monosynaptically connected to antagonistic muscles) are mutually inhibiting each other. The functional significance of this organization is discussed.", "contents": "Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. I. Disynaptic Ia inhibition of Ia inhibitory interneurones. Interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as \"Ia inhibitory interneurones\") were recorded in the lumbar spinal cord of the cat. It was revealed that the Ia inhibitory interneurones themselves receive disynaptic Ia inhibition. The muscles from which this inhibition is evoked are strictly antagonistic to those supplying their Ia excitation. Similar to the Ia inhibition in motoneurones the Ia inhibition in the Ia inhibitory interneurones is decreased when preceded by an antidromic stimulation of ventral roots. Furthermore, transmission of Ia inhibition to the Ia inhibitory interneurones is facilitated from ipsilateral and contralateral primary afferents as well as several supraspinal pathways analogous to earlier findings for the Ia inhibition of motoneurones. The pattern and control of the Ia inhibition of motoneurones and of Ia inhibitory interneurones display so striking similarities that it is suggested that identical interneurones are responsible. The conclusion thus emerges that \"opposite\" Ia inhibitory interneurones (i.e. interneurones monosynaptically connected to antagonistic muscles) are mutually inhibiting each other. The functional significance of this organization is discussed."} {"id": "PMID:1258670", "title": "Towards a valid technique of sampling fish muscle to determine redox substrates.", "content": "The redox substrates--lactate, malate, alpha-glycerophosphate, dihydroxy acetonephosphate and pyruvate--have been determined in liver and muscle tissue from young salmon. The redox quotients have also been calculated. The freeze clamping technique was used and reliable samples of fish muscle for the determination of lactate were obtained with the aid of a pair of pliers with a gear mechanism. It was established that the lactate content in the body muscle is in close agreement with that in the blood from rested salmon parr. The concentrations of redox substrates are in good agreement with those found in mammalian tissue. The determination of the content of glycogen in fish muscle is discussed in the light of the results obtained in this study.", "contents": "Towards a valid technique of sampling fish muscle to determine redox substrates. The redox substrates--lactate, malate, alpha-glycerophosphate, dihydroxy acetonephosphate and pyruvate--have been determined in liver and muscle tissue from young salmon. The redox quotients have also been calculated. The freeze clamping technique was used and reliable samples of fish muscle for the determination of lactate were obtained with the aid of a pair of pliers with a gear mechanism. It was established that the lactate content in the body muscle is in close agreement with that in the blood from rested salmon parr. The concentrations of redox substrates are in good agreement with those found in mammalian tissue. The determination of the content of glycogen in fish muscle is discussed in the light of the results obtained in this study."} {"id": "PMID:1258671", "title": "Regional distribution of blood flow in calf muscles of rat during passive stretch and sustained contraction.", "content": "The regional distribution and number of microspheres in the calf muscles of rat has been studied during isometric sustained contraction and in stretched uncontracted muscles in situ. Carbonized microspheres, 15 +/- 5 mum, were injected into the aortic arch and muscle blood flow arrested 6 sec later. The calf muscles were freeze sectioned (12 slices of 40 mum) and the microspheres counted microscopically. The microsphere concentration in the gastrocnemius and plantaris muscles during rest was 4.6 +/- 1.6 spheres/mm3 (mean +/- S.E.). One min after a standardized exercise programme the sphere concentration was increased to 20.5 +/- 3.9 spheres/mm3. At increasing force of contraction following the standard exercise programme, the microsphere concentration fell from 11.6 +/- 2.5 at 25% of maximal force of contraction (MFC) to 2.2 +/- 0.6 spheres/mm3 at 100% MFC (5.6 kg/cm2). Corresponding measurements in stretched, uncontracted muscles showed a similar fall in microsphere concentration in the central inner zone and in the peripheral outer zone was slightly higher than unity (1.08-1.16) in muscles at rest and at light postexercise hyperemia. At 75 and 100% MFC the ratio was 0.76 +/- 0.07 and 0.57 +/- 0.13, significantly lower than unity. Stretching of the uncontracted muscle group to 175% MFC reduced the ratio towards zero. The greater reduction in blood flow to the inner central zone of contracted calf muscles shown by microsphere distribution was confirmed by measurement of 125 I-antipyrine distribution. These results show an increased resistance against blood flow during active contraction or stretching of the calf muscles, most pronounced in the central inner zone at high tensions.", "contents": "Regional distribution of blood flow in calf muscles of rat during passive stretch and sustained contraction. The regional distribution and number of microspheres in the calf muscles of rat has been studied during isometric sustained contraction and in stretched uncontracted muscles in situ. Carbonized microspheres, 15 +/- 5 mum, were injected into the aortic arch and muscle blood flow arrested 6 sec later. The calf muscles were freeze sectioned (12 slices of 40 mum) and the microspheres counted microscopically. The microsphere concentration in the gastrocnemius and plantaris muscles during rest was 4.6 +/- 1.6 spheres/mm3 (mean +/- S.E.). One min after a standardized exercise programme the sphere concentration was increased to 20.5 +/- 3.9 spheres/mm3. At increasing force of contraction following the standard exercise programme, the microsphere concentration fell from 11.6 +/- 2.5 at 25% of maximal force of contraction (MFC) to 2.2 +/- 0.6 spheres/mm3 at 100% MFC (5.6 kg/cm2). Corresponding measurements in stretched, uncontracted muscles showed a similar fall in microsphere concentration in the central inner zone and in the peripheral outer zone was slightly higher than unity (1.08-1.16) in muscles at rest and at light postexercise hyperemia. At 75 and 100% MFC the ratio was 0.76 +/- 0.07 and 0.57 +/- 0.13, significantly lower than unity. Stretching of the uncontracted muscle group to 175% MFC reduced the ratio towards zero. The greater reduction in blood flow to the inner central zone of contracted calf muscles shown by microsphere distribution was confirmed by measurement of 125 I-antipyrine distribution. These results show an increased resistance against blood flow during active contraction or stretching of the calf muscles, most pronounced in the central inner zone at high tensions."} {"id": "PMID:1258672", "title": "Signal characteristics of EMG at different levels of muscle tension.", "content": "Electromyographic activity of m. rectus femoris at submaximal and maximal voluntary contractions was quantified by conventional integration technique and also be a more \"qualitative\" procedure of automated motor unit averaging and frequency spectrum analysis. By relating the EMG parameters to produced muscle tension it was observed that the integrated EMG increased in a slightly nonlinear fashion with the increase in muscle force. The other EMG variables also showed clear changes as a function of muscle tension. The averaged motor unit potential (AMUP) and its specific parameters (number of spikes, amplitude, rise time and amplitude-rise time ratio) showed such changes with muscle tension that they may be useful in estimation of the recruitment pattern of the different types of motor units.", "contents": "Signal characteristics of EMG at different levels of muscle tension. Electromyographic activity of m. rectus femoris at submaximal and maximal voluntary contractions was quantified by conventional integration technique and also be a more \"qualitative\" procedure of automated motor unit averaging and frequency spectrum analysis. By relating the EMG parameters to produced muscle tension it was observed that the integrated EMG increased in a slightly nonlinear fashion with the increase in muscle force. The other EMG variables also showed clear changes as a function of muscle tension. The averaged motor unit potential (AMUP) and its specific parameters (number of spikes, amplitude, rise time and amplitude-rise time ratio) showed such changes with muscle tension that they may be useful in estimation of the recruitment pattern of the different types of motor units."} {"id": "PMID:1258673", "title": "Myocardial blood flow in the diving seal.", "content": "Grey seals exhibit a marked drop in heart rate, a slight decrease in ventricular contractility, and an essentially unchanged stroke volume upon diving. In the present study, we have demonstrated that the resulting drop in cardiac output is associated with a 90% reduction of coronary blood flow. Such reduction of myocardial blood flow takes place despite a significant increase in effective coronary driving pressure, and is indicative of a 800% increase in coronary vascular resistance. This means that the circulatory adjustments displayed by the diving seal (i.e. a reduction of the workload on the heart) are so effective that myocardial blood flow can be reduced to 10% of the pre-dive value without loss of cardiac function and blood pressure. It is suggested that even partial simulation of such a circulatory state might be a successful approach in the treatment of ischemic injuries in the heart of man.", "contents": "Myocardial blood flow in the diving seal. Grey seals exhibit a marked drop in heart rate, a slight decrease in ventricular contractility, and an essentially unchanged stroke volume upon diving. In the present study, we have demonstrated that the resulting drop in cardiac output is associated with a 90% reduction of coronary blood flow. Such reduction of myocardial blood flow takes place despite a significant increase in effective coronary driving pressure, and is indicative of a 800% increase in coronary vascular resistance. This means that the circulatory adjustments displayed by the diving seal (i.e. a reduction of the workload on the heart) are so effective that myocardial blood flow can be reduced to 10% of the pre-dive value without loss of cardiac function and blood pressure. It is suggested that even partial simulation of such a circulatory state might be a successful approach in the treatment of ischemic injuries in the heart of man."} {"id": "PMID:1258697", "title": "Bacteriological and clinical evaluation of different dialysate delivery systems.", "content": "In the period 1964-74 four different dialysate delivery systems have been used in our department. 1) Central mixing of dialysate using tap water and a dialysate delivery line with \"dead ends\" resulting in stagnant dialysate. 2) Central mixing of dialysate with cold distilled water, otherwise equal to system 1. 3) Local mixing of dialysate with cold distilled water, delivered through a line with \"dead ends\" resulting in stagnant water. 4) Local mixing of dialysate with distilled water, cooled to 25 degrees C just prior to use, reduced \"dead ends\" and monitored constant overflow to drain through the water supply line. The bacterial contamination of the four systems was examined and related to the clinical occurrence of pyrogenic and other reactions. An improvement was noted with the change from central to local mixing of dialysate (system 3) but complete sterility and virtual freedom from clinical reactions were first obtained in system 4. It is concluded that the use of sterile or near sterile dialysate is recommendable.", "contents": "Bacteriological and clinical evaluation of different dialysate delivery systems. In the period 1964-74 four different dialysate delivery systems have been used in our department. 1) Central mixing of dialysate using tap water and a dialysate delivery line with \"dead ends\" resulting in stagnant dialysate. 2) Central mixing of dialysate with cold distilled water, otherwise equal to system 1. 3) Local mixing of dialysate with cold distilled water, delivered through a line with \"dead ends\" resulting in stagnant water. 4) Local mixing of dialysate with distilled water, cooled to 25 degrees C just prior to use, reduced \"dead ends\" and monitored constant overflow to drain through the water supply line. The bacterial contamination of the four systems was examined and related to the clinical occurrence of pyrogenic and other reactions. An improvement was noted with the change from central to local mixing of dialysate (system 3) but complete sterility and virtual freedom from clinical reactions were first obtained in system 4. It is concluded that the use of sterile or near sterile dialysate is recommendable."} {"id": "PMID:1258698", "title": "Survival after portacaval shunt: who and how?", "content": "In a series of 74 portacaval-shunted patients no statistically significant differences in long-term survival or in incidence of postoperative encephalopathy have been observed between electively and emergency operated patients, between patients with slight and moderate impairment of liver function (groups A and B according to Child) or between patients with alcoholic and non-alcoholic cirrhosis. Patients older than 60 years had a higher risk of postoperative encephalopathy and a border-line significantly lower survival rate six months after the operation. Among the patients with more than six months' survival, about 50% returned to work.", "contents": "Survival after portacaval shunt: who and how? In a series of 74 portacaval-shunted patients no statistically significant differences in long-term survival or in incidence of postoperative encephalopathy have been observed between electively and emergency operated patients, between patients with slight and moderate impairment of liver function (groups A and B according to Child) or between patients with alcoholic and non-alcoholic cirrhosis. Patients older than 60 years had a higher risk of postoperative encephalopathy and a border-line significantly lower survival rate six months after the operation. Among the patients with more than six months' survival, about 50% returned to work."} {"id": "PMID:1258699", "title": "Peripheral circulation, particularly heat regulation reactions, in patients with amyloidosis and polyneuropathy.", "content": "As patients with amyloidosis and polyneuropathy often have signs and symptoms of circulatory disturbances in the extremities, especially the legs, we have examined such patients and controls with oscillometry and digital pulse plethysmography in order to estimate the occurrence of any arterial circulatory insufficiency. No signs of significant obliterative arterial changes were found. Skin temperature was also determined in fingers and toes during body-cooling and at subsequent indirect heating. At low environmental temperature the skin temperature was higher in patients than in controls. In a few patients there was almost no decrease in skin temperature, despite a long period of cooling and a low rectal temperature. Indirect heating elicited a marked increase in the skin temperature of the toes and fingers of the controls. In most patients this reaction was completely absent in the toes and absent or reduced in the fingers. These deviations can be explained by nerve damage caused by amyloid deposition in the nerves. Amyloid deposits in the wall of small blood vessels may be an additional factor. Maximum blood flow in the anterior tibial muscle after combined ischemia and exercise, investigated with radioactive xenon, was reduced in half of the patients.", "contents": "Peripheral circulation, particularly heat regulation reactions, in patients with amyloidosis and polyneuropathy. As patients with amyloidosis and polyneuropathy often have signs and symptoms of circulatory disturbances in the extremities, especially the legs, we have examined such patients and controls with oscillometry and digital pulse plethysmography in order to estimate the occurrence of any arterial circulatory insufficiency. No signs of significant obliterative arterial changes were found. Skin temperature was also determined in fingers and toes during body-cooling and at subsequent indirect heating. At low environmental temperature the skin temperature was higher in patients than in controls. In a few patients there was almost no decrease in skin temperature, despite a long period of cooling and a low rectal temperature. Indirect heating elicited a marked increase in the skin temperature of the toes and fingers of the controls. In most patients this reaction was completely absent in the toes and absent or reduced in the fingers. These deviations can be explained by nerve damage caused by amyloid deposition in the nerves. Amyloid deposits in the wall of small blood vessels may be an additional factor. Maximum blood flow in the anterior tibial muscle after combined ischemia and exercise, investigated with radioactive xenon, was reduced in half of the patients."} {"id": "PMID:1258700", "title": "Skin lesions of the legs and feet and skeletal lesions of the feet in familail amyloidosis with polyneuropathy.", "content": "Twenty-one patients with familial amyloidosis and polyneuropathy have been examined for the presence of skin lesions, localized to the lower legs and feet. The lesions were classified as atrophic skin lesions, hypertrophic scar-like skin lesions, rubeosis plantarum, spontaneous blisters, necrotic skin lesions, yellow nails, traumatic skin lesions, purpura and abundant pigmented small non-atrophic spots. Skeletal destructions in the feet were also demonstrated. In many respects these lesions are similar to those of long-standing diabetes mellitus. I studied the cutaneous reactions to local thermal trauma with heat and cold to the legs and forearms in 11 patients. Petechiae were observed within the area of traumatization with either heat or cold more often in patients than in controls. Four of the 11 patients developed atrophic circumscribed skin lesions at the site of traumatization.", "contents": "Skin lesions of the legs and feet and skeletal lesions of the feet in familail amyloidosis with polyneuropathy. Twenty-one patients with familial amyloidosis and polyneuropathy have been examined for the presence of skin lesions, localized to the lower legs and feet. The lesions were classified as atrophic skin lesions, hypertrophic scar-like skin lesions, rubeosis plantarum, spontaneous blisters, necrotic skin lesions, yellow nails, traumatic skin lesions, purpura and abundant pigmented small non-atrophic spots. Skeletal destructions in the feet were also demonstrated. In many respects these lesions are similar to those of long-standing diabetes mellitus. I studied the cutaneous reactions to local thermal trauma with heat and cold to the legs and forearms in 11 patients. Petechiae were observed within the area of traumatization with either heat or cold more often in patients than in controls. Four of the 11 patients developed atrophic circumscribed skin lesions at the site of traumatization."} {"id": "PMID:1258701", "title": "Purpura, pigmentation and yellow nails of the lower extremities in diabetics.", "content": "This article describes purpura and pigmentations of the lower extremities as well as yellow nails mainly in elderly diabetics but also in persons not known to have diabetes. When the latter were compared to controls, it appeared that their glucose tolerance was altered in a diabetic direction. Precipitating factors could generally be established for these lesions, predominantly cardiac decompensation with edema of the legs, and were more common in patients not known to have open diabetes than in patients with open diabetes. Petechiae were transformed into small, pigmented, non-atrophic spots. Petechiae and pigmented spots were often seen simultaneously. In a few patients small, pigmented, non-atrophic spots were seen as pronounced brown-black pigmentation of the lower legs and feet. In a number of patients with open diabetes or diabetic glucose tolerance, erysipelas with purpura within the area of erysipelas was observed on the lower extremities. Patients with no purpura within the area of erysipelas generally had normal glucose tolerance. The pathogenesis of these lesions is discussed. Atrophic circumscribed skin lesions (Melin), cutaneous erythema, with or without necrosis, purpura, pigmentation, red toes, as well as rubeosis plantarum, yellow nails and neuropathy are often seen simultaneously on the lower extremities of patients with open diabetes as well as of those without open diabetes but with diabetic glucose tolerance.", "contents": "Purpura, pigmentation and yellow nails of the lower extremities in diabetics. This article describes purpura and pigmentations of the lower extremities as well as yellow nails mainly in elderly diabetics but also in persons not known to have diabetes. When the latter were compared to controls, it appeared that their glucose tolerance was altered in a diabetic direction. Precipitating factors could generally be established for these lesions, predominantly cardiac decompensation with edema of the legs, and were more common in patients not known to have open diabetes than in patients with open diabetes. Petechiae were transformed into small, pigmented, non-atrophic spots. Petechiae and pigmented spots were often seen simultaneously. In a few patients small, pigmented, non-atrophic spots were seen as pronounced brown-black pigmentation of the lower legs and feet. In a number of patients with open diabetes or diabetic glucose tolerance, erysipelas with purpura within the area of erysipelas was observed on the lower extremities. Patients with no purpura within the area of erysipelas generally had normal glucose tolerance. The pathogenesis of these lesions is discussed. Atrophic circumscribed skin lesions (Melin), cutaneous erythema, with or without necrosis, purpura, pigmentation, red toes, as well as rubeosis plantarum, yellow nails and neuropathy are often seen simultaneously on the lower extremities of patients with open diabetes as well as of those without open diabetes but with diabetic glucose tolerance."} {"id": "PMID:1258702", "title": "Sarcoidosis. A clinical study with special reference to the choice of biopsy procedure.", "content": "In a 10-year review of the records of 146 young male patients suspected of sarcoidosis on the basis of radiographic intrathoracic changes, the chest X-ray findings have been analysed in relation to the results of different biopsies. Most of the patients were military men, and almost all were apparently affected by the disease. Sixty-six per cent had bilateral hilar lymphadenopathy (BHL) only, 12% had isolated pulmonary lesions and 22% had both BHL and pulmonary lesions. In all patients at least one biopsy was performed, in most cases a scalene fat pad biopsy and/or a liver biopsy. Epitheloid cell granulomas were demonstrated in 86 biopsies from 64 of the 146 patients. Granulomas were obtained more frequently by scalene fat pad biopsies than by liver biopsies in the same group of patients. During the first 4--5 years of the 10-year period the scalene fat pad biopsies were done in local anesthesia in different general surgical departments without special experience of this biopsy procedure. In the last 5--6 years the scalene fat pad biopsies were done in general anaesthesia in a head and neck surgical department specially trained in this biopsy technique. Granulomas were obtained more frequently in the latter than in the former group. The highest frequency of granulomas was found among patients with both BHL and pulmonary lesions. Of the 71 patients in whom liver biopsy was performed, 43% had granulomas in the liver. A few patients had signs--although only slight--of liver affection. The results of the different biopsies are discussed in relation to the clinical picture. It is concluded that scalene fat pad biopsy in some cases can still be of some diagnostic aid in patients with radiographic intrathoracic changes suspected of sarcoidosis, although this type of biopsy has to a great extent been replaced by biopsy through mediastinoscopy. Furthermore it is concluded that comparison of different biopsies in one and the same patient could elucidate a possible relationship between the radiographic intrathoracic manifestations and the occurrence of granulomas in different intra- and extra-thoracic tissues. In this study there were only few and insignificant complications of the biopsies.", "contents": "Sarcoidosis. A clinical study with special reference to the choice of biopsy procedure. In a 10-year review of the records of 146 young male patients suspected of sarcoidosis on the basis of radiographic intrathoracic changes, the chest X-ray findings have been analysed in relation to the results of different biopsies. Most of the patients were military men, and almost all were apparently affected by the disease. Sixty-six per cent had bilateral hilar lymphadenopathy (BHL) only, 12% had isolated pulmonary lesions and 22% had both BHL and pulmonary lesions. In all patients at least one biopsy was performed, in most cases a scalene fat pad biopsy and/or a liver biopsy. Epitheloid cell granulomas were demonstrated in 86 biopsies from 64 of the 146 patients. Granulomas were obtained more frequently by scalene fat pad biopsies than by liver biopsies in the same group of patients. During the first 4--5 years of the 10-year period the scalene fat pad biopsies were done in local anesthesia in different general surgical departments without special experience of this biopsy procedure. In the last 5--6 years the scalene fat pad biopsies were done in general anaesthesia in a head and neck surgical department specially trained in this biopsy technique. Granulomas were obtained more frequently in the latter than in the former group. The highest frequency of granulomas was found among patients with both BHL and pulmonary lesions. Of the 71 patients in whom liver biopsy was performed, 43% had granulomas in the liver. A few patients had signs--although only slight--of liver affection. The results of the different biopsies are discussed in relation to the clinical picture. It is concluded that scalene fat pad biopsy in some cases can still be of some diagnostic aid in patients with radiographic intrathoracic changes suspected of sarcoidosis, although this type of biopsy has to a great extent been replaced by biopsy through mediastinoscopy. Furthermore it is concluded that comparison of different biopsies in one and the same patient could elucidate a possible relationship between the radiographic intrathoracic manifestations and the occurrence of granulomas in different intra- and extra-thoracic tissues. In this study there were only few and insignificant complications of the biopsies."} {"id": "PMID:1258703", "title": "Vectorcardiographic-hemodynamic correlations in adult aortic stenosis.", "content": "Thirty-nine vectorcardiographic (VCG) data from 45 patients with pure adult aortic stenosis have been tested as to their ability to reflect quantitatively the peak systolic left ventricular pressure (LVPSP), the left ventricular end diastolic pressure (LVEDP), and the X-ray estimated heart volume. VCG was recorded with the axial lead system and simple and multiple linear regression analyses were applied. Eight VCG data correlated significantly (p less than 0.001) with LVPSP, the best indicator being the maximum posterior dislocation in the Z lead (r = 0.65). Through multiple regression analysis a formula was derived which gave a correlation coefficient between observed and calculated pressures of 0.82. The best indicator of LVEDP was the maximum positive P amplitude in the X lead (r = 0.41). The relationship was, however, too poor to have practical significance. A good correlation was found between ST segment dislocation and heart volume (r = 0.65), in good accordance with previous observations as to the effect of right ventricular dilatation on the ECG. The study illustrates how ventricular volume and pressure exert different effects on the ECG, and how all the important hemodynamic aspects in aortic stenosis to some degree are reflected. Only the pressure correlations have, however, practical importance.", "contents": "Vectorcardiographic-hemodynamic correlations in adult aortic stenosis. Thirty-nine vectorcardiographic (VCG) data from 45 patients with pure adult aortic stenosis have been tested as to their ability to reflect quantitatively the peak systolic left ventricular pressure (LVPSP), the left ventricular end diastolic pressure (LVEDP), and the X-ray estimated heart volume. VCG was recorded with the axial lead system and simple and multiple linear regression analyses were applied. Eight VCG data correlated significantly (p less than 0.001) with LVPSP, the best indicator being the maximum posterior dislocation in the Z lead (r = 0.65). Through multiple regression analysis a formula was derived which gave a correlation coefficient between observed and calculated pressures of 0.82. The best indicator of LVEDP was the maximum positive P amplitude in the X lead (r = 0.41). The relationship was, however, too poor to have practical significance. A good correlation was found between ST segment dislocation and heart volume (r = 0.65), in good accordance with previous observations as to the effect of right ventricular dilatation on the ECG. The study illustrates how ventricular volume and pressure exert different effects on the ECG, and how all the important hemodynamic aspects in aortic stenosis to some degree are reflected. Only the pressure correlations have, however, practical importance."} {"id": "PMID:1258704", "title": "A nitrofurantoin-induced disorder simulating chronic active hepatitis. A case report.", "content": "A 78-year-old woman with liver damage resembling chronic active hepatitis and occuring during long-term nitrofurantoin treatment is described. On admission to hospital she displayed jaundice, ascites and high serum levels of GOT, GPT, bilirubin and gamma-globulin as well as high titres of ANF and antibodies against smooth muscle cells. After withdrawal of nitrofurantoin the clinical and laboratory picture normalized without corticosteroid treatment, suggesting that the liver reaction was drug-induced.", "contents": "A nitrofurantoin-induced disorder simulating chronic active hepatitis. A case report. A 78-year-old woman with liver damage resembling chronic active hepatitis and occuring during long-term nitrofurantoin treatment is described. On admission to hospital she displayed jaundice, ascites and high serum levels of GOT, GPT, bilirubin and gamma-globulin as well as high titres of ANF and antibodies against smooth muscle cells. After withdrawal of nitrofurantoin the clinical and laboratory picture normalized without corticosteroid treatment, suggesting that the liver reaction was drug-induced."} {"id": "PMID:1258706", "title": "Factors controlling growth and age involution of the rat thymus.", "content": "Thymic development and somatic growth were investigated in three strains of rat. The well established influence of sex and age on somatic growth was confirmed. It was also found that the rate of thymic growth was not influenced by the sex of the animal until four weeks of age, but thereafter, the thymus grew faster in males compared with females of the same strain. Gonadectomy had a marked effect on the thymus, resulting in a higher rate of growth than in normal animals; but a slower initial rate of involution. The maximum thymus weights attained in gonadectomized animals were found to be independent of the age at which the animals were gonadectomized or of the sex of the animal. Gonadectomy did not influence the point at which involution began. Thymic mitotic indices of gonadectomized animals were found to be higher than those of normal animals. The influence of sex hormones on somatic growth and the development of the thymus is discussed, and it is concluded that cell loss is the regulator of thumus growth and involution.", "contents": "Factors controlling growth and age involution of the rat thymus. Thymic development and somatic growth were investigated in three strains of rat. The well established influence of sex and age on somatic growth was confirmed. It was also found that the rate of thymic growth was not influenced by the sex of the animal until four weeks of age, but thereafter, the thymus grew faster in males compared with females of the same strain. Gonadectomy had a marked effect on the thymus, resulting in a higher rate of growth than in normal animals; but a slower initial rate of involution. The maximum thymus weights attained in gonadectomized animals were found to be independent of the age at which the animals were gonadectomized or of the sex of the animal. Gonadectomy did not influence the point at which involution began. Thymic mitotic indices of gonadectomized animals were found to be higher than those of normal animals. The influence of sex hormones on somatic growth and the development of the thymus is discussed, and it is concluded that cell loss is the regulator of thumus growth and involution."} {"id": "PMID:1258708", "title": "Red-blood-cell potassium as a practical index of potassium status in elderly patients.", "content": "Red-blood-cell potassium has been measured using a simplified technique on 292 geriatric patients. The measurement was found useful in reflecting changes in potassium status whereas serum potassium was unhelpful.", "contents": "Red-blood-cell potassium as a practical index of potassium status in elderly patients. Red-blood-cell potassium has been measured using a simplified technique on 292 geriatric patients. The measurement was found useful in reflecting changes in potassium status whereas serum potassium was unhelpful."} {"id": "PMID:1258709", "title": "Hypoglycaemic coma due to chlorpropamide: observations on twenty-two patients.", "content": "Twenty-two patients with chlorpropamide-induced hypoglycaemic coma were seen at a medical centre serving a region with a large geriatric population. The median age of the patients was 72; seven were over 80 and only one was under 60. Four patients died and in three of them death appeared to be connected with the hypoglycaemia. In two cases, the hypoglycaemia appeared in the postoperative period. Generally accepted contra-indications to the use of chlorpropamide were present in five of the eight patients under 70 and in four of the 14 patients over 70. If full precautions had been taken in presecribing chlorpropamide and if old age had been regarded as a contra-indication, the hypoglycaemia might have been prevented in 19 out of the 22 patients.", "contents": "Hypoglycaemic coma due to chlorpropamide: observations on twenty-two patients. Twenty-two patients with chlorpropamide-induced hypoglycaemic coma were seen at a medical centre serving a region with a large geriatric population. The median age of the patients was 72; seven were over 80 and only one was under 60. Four patients died and in three of them death appeared to be connected with the hypoglycaemia. In two cases, the hypoglycaemia appeared in the postoperative period. Generally accepted contra-indications to the use of chlorpropamide were present in five of the eight patients under 70 and in four of the 14 patients over 70. If full precautions had been taken in presecribing chlorpropamide and if old age had been regarded as a contra-indication, the hypoglycaemia might have been prevented in 19 out of the 22 patients."} {"id": "PMID:1258710", "title": "The problems of motor neurone disease.", "content": "The course of Motor Neurone Disease (MND) is described in 22 patients in respect of the extent and duration of the disabilities. The average stay in hospital in the terminal phase in 20 patients followed to the time of their death was 6.6 months for men and 4.7 months for women. The total duration of the disease ranged from 11 to 45 months, with an average of 28.7 months for men and 22.2 months for women. Between the bulbar cervical lumbar and mixed forms of the disease at the onset there emerged no difference in average survival. On woman of 32 is still alive 10 years after the onset, and one after 2-1/2 years. The hospital staff were exposed over many months to the progressive deterioration in breathing, swallowing, posture and mobility, and emotional crises and dysarthria aggravated the problems of management. Pain was a feature in one-third of the patients. In the treatment, physiotherapy with the accent on passive movements was found helpful. Although formal occupational therapy was not accepted by half of the patients, it was important to talk to them frequently, and encourage any means of expression such as painting, writing or dictating diaries, poems or essays. The indications for gastrostomy feeding are discussed, and the problem is raised of assisted respiration in this disease.", "contents": "The problems of motor neurone disease. The course of Motor Neurone Disease (MND) is described in 22 patients in respect of the extent and duration of the disabilities. The average stay in hospital in the terminal phase in 20 patients followed to the time of their death was 6.6 months for men and 4.7 months for women. The total duration of the disease ranged from 11 to 45 months, with an average of 28.7 months for men and 22.2 months for women. Between the bulbar cervical lumbar and mixed forms of the disease at the onset there emerged no difference in average survival. On woman of 32 is still alive 10 years after the onset, and one after 2-1/2 years. The hospital staff were exposed over many months to the progressive deterioration in breathing, swallowing, posture and mobility, and emotional crises and dysarthria aggravated the problems of management. Pain was a feature in one-third of the patients. In the treatment, physiotherapy with the accent on passive movements was found helpful. Although formal occupational therapy was not accepted by half of the patients, it was important to talk to them frequently, and encourage any means of expression such as painting, writing or dictating diaries, poems or essays. The indications for gastrostomy feeding are discussed, and the problem is raised of assisted respiration in this disease."} {"id": "PMID:1258711", "title": "Geriatric admissions in East London 1962-72.", "content": "Geriatric admissions over the period 1962-72 in East London were studied. Patients, for the most part, presented combinations of physical, mental and social disability. 6286 admissions of 3988 patients were analysed with regard to length of stay, outcome, number of repeat admissions, age and sex. Numbers were large enough for trends to be clear. For example, 550 admissions were of persons over 90. The largest group were aged 75-84. The likelihood of death in hospital increased with age while the percentage of discharges home fell. With age there was a gradual increase in the percentage of those in hospital 28 days or less. Eight per cent of males and 10 per cent of females remained in hospital over one year. Seventy per cent of patients were admitted to hospital once only, while fewer than 2 per cent were admitted more than five times. A sample of new patients admitted from one borough in 1968, was traced in hospital and after discharge. The 50 per cent survival time for men was 6.5 months and for women 12.9 months.", "contents": "Geriatric admissions in East London 1962-72. Geriatric admissions over the period 1962-72 in East London were studied. Patients, for the most part, presented combinations of physical, mental and social disability. 6286 admissions of 3988 patients were analysed with regard to length of stay, outcome, number of repeat admissions, age and sex. Numbers were large enough for trends to be clear. For example, 550 admissions were of persons over 90. The largest group were aged 75-84. The likelihood of death in hospital increased with age while the percentage of discharges home fell. With age there was a gradual increase in the percentage of those in hospital 28 days or less. Eight per cent of males and 10 per cent of females remained in hospital over one year. Seventy per cent of patients were admitted to hospital once only, while fewer than 2 per cent were admitted more than five times. A sample of new patients admitted from one borough in 1968, was traced in hospital and after discharge. The 50 per cent survival time for men was 6.5 months and for women 12.9 months."} {"id": "PMID:1258712", "title": "Contraception for adolescents.", "content": "The two major groups of contraceptives available to adolescents are simple and prescribed methods. Of the former, spermicidal agents and condoms alone or in combination offer some protection. Of the prescribed methods, oral contraceptives and intrauterine devices offer best protection. The risk of pregnancy and the mortality and pathologic risks involved in the use of each method must be considered. The indications, contraindications and specific guidelines for prescribing contraceptives in this age group cannot be uniformly applied to all adolescents; therefore, individualization is always necessary.", "contents": "Contraception for adolescents. The two major groups of contraceptives available to adolescents are simple and prescribed methods. Of the former, spermicidal agents and condoms alone or in combination offer some protection. Of the prescribed methods, oral contraceptives and intrauterine devices offer best protection. The risk of pregnancy and the mortality and pathologic risks involved in the use of each method must be considered. The indications, contraindications and specific guidelines for prescribing contraceptives in this age group cannot be uniformly applied to all adolescents; therefore, individualization is always necessary."} {"id": "PMID:1258713", "title": "Hospital electrical safety.", "content": "Electrocution is an environmental hazard for hospital personnel and patients. The source is low-level alternating current, accidentally applied through indwelling electrodes which invade the normally protective high resistance of the body. Probably the greatest offender is the combination of electronic monitoring and the electrically operated bed. Preventive measures include education of medical personnel and the establishment of guidelines on leakage, coupled with periodic maintenance and inspection by trained technicians.", "contents": "Hospital electrical safety. Electrocution is an environmental hazard for hospital personnel and patients. The source is low-level alternating current, accidentally applied through indwelling electrodes which invade the normally protective high resistance of the body. Probably the greatest offender is the combination of electronic monitoring and the electrically operated bed. Preventive measures include education of medical personnel and the establishment of guidelines on leakage, coupled with periodic maintenance and inspection by trained technicians."} {"id": "PMID:1258719", "title": "Tetanus.", "content": "While the incidence of clinical tetanus had decreased greatly, efforts to eradicate the disease will depend mainly upon continued stress on prophylaxis. Recent cases demonstrate the need for both continued vigil in prophylaxis and sensitivity to the early signs of the clinical disease. The fundamentals of treatment are: neutralize formed toxin, eradicate Clostridium tetani, debride tissues adequately, control spasm and start immunization. Complications are legion. Mortality is highest in the very young and in the elderly.", "contents": "Tetanus. While the incidence of clinical tetanus had decreased greatly, efforts to eradicate the disease will depend mainly upon continued stress on prophylaxis. Recent cases demonstrate the need for both continued vigil in prophylaxis and sensitivity to the early signs of the clinical disease. The fundamentals of treatment are: neutralize formed toxin, eradicate Clostridium tetani, debride tissues adequately, control spasm and start immunization. Complications are legion. Mortality is highest in the very young and in the elderly."} {"id": "PMID:1258720", "title": "Constipation in childhood.", "content": "Most commonly, constipation in the infant is functional, with increased tone of colonic smooth muscle. Hirschsprung's disease is the best known of the infrequent organic causes. Treatment includes reassurance of parents, use of sugars, fluids and bulk and care of fissures. Voluntary stool withholding occurs in older children, who present with a variety of symptoms. Medicines are required to restore the functional capacity of the colon after chronic distortion by stool. This must be combined with psychologic help.", "contents": "Constipation in childhood. Most commonly, constipation in the infant is functional, with increased tone of colonic smooth muscle. Hirschsprung's disease is the best known of the infrequent organic causes. Treatment includes reassurance of parents, use of sugars, fluids and bulk and care of fissures. Voluntary stool withholding occurs in older children, who present with a variety of symptoms. Medicines are required to restore the functional capacity of the colon after chronic distortion by stool. This must be combined with psychologic help."} {"id": "PMID:1258722", "title": "Erythema nodosum.", "content": "Erythema nodosum (EN) is now more commonly associated with streptococcal disease than with tuberculosis. Sarcoidosis is the third most frequently associated systemic disease. Oral contraceptives now lead the list of drugs associated with EN. The appearance and disappearance of crops of nodules is extremely variable. Salicylates and rest are useful. Steroids are not recommended because they may compromise defenses against an underlying disease process.", "contents": "Erythema nodosum. Erythema nodosum (EN) is now more commonly associated with streptococcal disease than with tuberculosis. Sarcoidosis is the third most frequently associated systemic disease. Oral contraceptives now lead the list of drugs associated with EN. The appearance and disappearance of crops of nodules is extremely variable. Salicylates and rest are useful. Steroids are not recommended because they may compromise defenses against an underlying disease process."} {"id": "PMID:1258724", "title": "Preclinical cardiomyopathy in chronic alcoholics: a sex difference.", "content": "Alcoholic subjects differ in the incidence of cardiomyopathy. Of potential variables, sex may be important since few females are seen with cardiomyopathy, even adjusting for the lower incidence of alcoholism. To examine this question, noninvasive systolic time intervals were measured in 22 males and 14 females of similar age, heart rate, and arterial pressure, without clinical evidence of heart disease or hypertrophy. Duration and intensity of ethanol intake and the interval from last drinking episode were apparently equivalent. In male alcoholics, the left ventricular preejection period and ejection time (PEP/LVET) ratio of 0.410 +/- 0.020 was significantly higher than in the 11 normal males (0.316 +/- 0.007) (P less than 0.001). In female alcoholics, the ratio was 0.322 +/- 0.015, compared to 0.310 +/- 0.01 for 11 normal females, and was significantly less than in the male patients (P +/- 0.001). In addition prolonged intraventricular conduction by high-frequency ECG was more prevalent in the male group. To further ensure equivalency of alcoholism, patients with biopsy-proved cirrhosis were selected. In nine males, PEP/LVET was significantly higher than in the 10 females. Thus, abnormal myocardial function was evident in males but not in females, suggesting that sex is a determinant of the toxic effects of ethanol on myocardium.", "contents": "Preclinical cardiomyopathy in chronic alcoholics: a sex difference. Alcoholic subjects differ in the incidence of cardiomyopathy. Of potential variables, sex may be important since few females are seen with cardiomyopathy, even adjusting for the lower incidence of alcoholism. To examine this question, noninvasive systolic time intervals were measured in 22 males and 14 females of similar age, heart rate, and arterial pressure, without clinical evidence of heart disease or hypertrophy. Duration and intensity of ethanol intake and the interval from last drinking episode were apparently equivalent. In male alcoholics, the left ventricular preejection period and ejection time (PEP/LVET) ratio of 0.410 +/- 0.020 was significantly higher than in the 11 normal males (0.316 +/- 0.007) (P less than 0.001). In female alcoholics, the ratio was 0.322 +/- 0.015, compared to 0.310 +/- 0.01 for 11 normal females, and was significantly less than in the male patients (P +/- 0.001). In addition prolonged intraventricular conduction by high-frequency ECG was more prevalent in the male group. To further ensure equivalency of alcoholism, patients with biopsy-proved cirrhosis were selected. In nine males, PEP/LVET was significantly higher than in the 10 females. Thus, abnormal myocardial function was evident in males but not in females, suggesting that sex is a determinant of the toxic effects of ethanol on myocardium."} {"id": "PMID:1258725", "title": "Atrioventricular conduction patterns in patients with paroxysmal supraventricular tachycardia.", "content": "Atrioventricular conduction patterns suggestive of dual A-V nodal pathways have been reported in patients with and without a history of paroxysmal A-V nodal re-entrant tachycardia (PSVT). The purpose of this study was to determine whether significant association exists between this conduction pattern and the occurrence of PSVT in man. The pattern of A-V conduction was evaluated at similar pacing rates in 13 patients with documented PSVT and 135 patients with PSVT. Patients without PSVT were divided into groups with normal PR intervals (106 patients), PR intervals of 120 msec. or less (12 patients), and PR intervals of 200 msec. or greater (17 patients). Evidence of dual A-V nodal pathways was found in seven of 13 patients with PSVT and nine of 135 patients without PSVT, including eight of 106 patients with normal PR intervals, none of 12 patients with short PR intervals, and one of 17 patients with PR intervals of 200 msec. or greater. The incidence of dual A-V nodal pathways was significantly greater (P less than 0.01) in patients with PSVT when compared with all other groups. In two of four patients with PSVT, propranolol was found to unmask evidence of dual pathways; no evidence of dual pathways was produced by propranolol in 23 patients without PSVT. The data show that the pattern of dual A-V nodal pathways is common only in patients with PSVT and is significantly less frequent in patients without PSVT regardless of the presence of short or long PR intervals. The results of this study establish a strong association between this conduction pattern and the occurrence of PSVT in man.", "contents": "Atrioventricular conduction patterns in patients with paroxysmal supraventricular tachycardia. Atrioventricular conduction patterns suggestive of dual A-V nodal pathways have been reported in patients with and without a history of paroxysmal A-V nodal re-entrant tachycardia (PSVT). The purpose of this study was to determine whether significant association exists between this conduction pattern and the occurrence of PSVT in man. The pattern of A-V conduction was evaluated at similar pacing rates in 13 patients with documented PSVT and 135 patients with PSVT. Patients without PSVT were divided into groups with normal PR intervals (106 patients), PR intervals of 120 msec. or less (12 patients), and PR intervals of 200 msec. or greater (17 patients). Evidence of dual A-V nodal pathways was found in seven of 13 patients with PSVT and nine of 135 patients without PSVT, including eight of 106 patients with normal PR intervals, none of 12 patients with short PR intervals, and one of 17 patients with PR intervals of 200 msec. or greater. The incidence of dual A-V nodal pathways was significantly greater (P less than 0.01) in patients with PSVT when compared with all other groups. In two of four patients with PSVT, propranolol was found to unmask evidence of dual pathways; no evidence of dual pathways was produced by propranolol in 23 patients without PSVT. The data show that the pattern of dual A-V nodal pathways is common only in patients with PSVT and is significantly less frequent in patients without PSVT regardless of the presence of short or long PR intervals. The results of this study establish a strong association between this conduction pattern and the occurrence of PSVT in man."} {"id": "PMID:1258726", "title": "The significance of mitral valve prolapse in middle-aged and elderly men.", "content": "The clinical, roentgenographic, phonocardiographic, ECG, and echocardiographic data were evaluated in 40 consecutive middle-aged and elderly male patients with echocardiographically detectable systolic prolapse of mitral valve leaflets. Prolapse was present during more than half of systole in 31 patients and was holosystolic in six patients. In most instances, both leaflets prolapsed during systole. The closing velocity and excursion of the anterior leaflet were frequently increased particularly in association with evidence of mitral insufficiency. A majority of the patients had cardiac symptomatology. Moreover, roentgenographic and/or ECG evidence of cardiac enlargement or hypertrophy was evident in 45 percent of patients with mitral valve prolapse.", "contents": "The significance of mitral valve prolapse in middle-aged and elderly men. The clinical, roentgenographic, phonocardiographic, ECG, and echocardiographic data were evaluated in 40 consecutive middle-aged and elderly male patients with echocardiographically detectable systolic prolapse of mitral valve leaflets. Prolapse was present during more than half of systole in 31 patients and was holosystolic in six patients. In most instances, both leaflets prolapsed during systole. The closing velocity and excursion of the anterior leaflet were frequently increased particularly in association with evidence of mitral insufficiency. A majority of the patients had cardiac symptomatology. Moreover, roentgenographic and/or ECG evidence of cardiac enlargement or hypertrophy was evident in 45 percent of patients with mitral valve prolapse."} {"id": "PMID:1258727", "title": "Adrenergic beta blockade and ECG changes in the systolic click murmur syndrome.", "content": "In an attempt to elucidate the ECG changes associated with the SCMS, we have applied the propranolol test in 35 of our patients suffering from this syndrome. To the best of our knowledge this is the first such report in the English literature. Twenty-eight patients showed improvement and this points against an ischemic etiology. The test may be applied to differentiate ischemic ST-T changes from those associated with the SCMS. We have suggested the possibility of sympathetic overactivity and autonomic imbalance as the basis for the ECG and other features related to the SCMS. We have noted the striking similarities in the symptomatology and ECG changes associated with the SCMS and those of neurocirculatory asthenia. The implication of this was discussed.", "contents": "Adrenergic beta blockade and ECG changes in the systolic click murmur syndrome. In an attempt to elucidate the ECG changes associated with the SCMS, we have applied the propranolol test in 35 of our patients suffering from this syndrome. To the best of our knowledge this is the first such report in the English literature. Twenty-eight patients showed improvement and this points against an ischemic etiology. The test may be applied to differentiate ischemic ST-T changes from those associated with the SCMS. We have suggested the possibility of sympathetic overactivity and autonomic imbalance as the basis for the ECG and other features related to the SCMS. We have noted the striking similarities in the symptomatology and ECG changes associated with the SCMS and those of neurocirculatory asthenia. The implication of this was discussed."} {"id": "PMID:1258728", "title": "First-degree sinoatrial heart block: sinoatrial block in the sick-sinus syndrome.", "content": "Sinoatrial conduction time (SACT) was estimated from the delay in the atrial recovery period after premature depolarization applied in that portion of atrial diastole when increasing prematurity resulted in a constant recovery interval. In 20 normal patients SACT was 169 msec. +/- 91 (2 S.D.). At least nine of 19 patients with \"sick-sinus syndrome\" (SSS) demonstrated SACT that were longer than seen in these normal subjects. SACT was prolonged in seven of nine SSS patients with abnormal A-V nodal conduction. Among 10 SSS patients with normal A-V conduction, only two had prolonged SACT. This study identifies first-degree sinoatrial block as a frequent manifestation of SSS associated with the presence of A-V node conduction abnormalities.", "contents": "First-degree sinoatrial heart block: sinoatrial block in the sick-sinus syndrome. Sinoatrial conduction time (SACT) was estimated from the delay in the atrial recovery period after premature depolarization applied in that portion of atrial diastole when increasing prematurity resulted in a constant recovery interval. In 20 normal patients SACT was 169 msec. +/- 91 (2 S.D.). At least nine of 19 patients with \"sick-sinus syndrome\" (SSS) demonstrated SACT that were longer than seen in these normal subjects. SACT was prolonged in seven of nine SSS patients with abnormal A-V nodal conduction. Among 10 SSS patients with normal A-V conduction, only two had prolonged SACT. This study identifies first-degree sinoatrial block as a frequent manifestation of SSS associated with the presence of A-V node conduction abnormalities."} {"id": "PMID:1258729", "title": "Long-term survival following aortic valve replacement.", "content": "Study was made of 95 survivors of aortic valve replacement during the early years of this procedure (1964 to 1970). The average follow-up time was 50.2 months. Survival was not related to hemodynamic parameters, such as cardiac index or left ventricular pressure, and did not appear to be influenced by the type of preoperative valve lesion. A history of angina pectoris and a New York Heart Association Class IV grouping were associated with shorter survival. Associated coronary artery disease was a leading cause of death in those patients surviving less than 2 years and angina pectoris the leading cause of morbidity in the long-term survivors. Sudden death occurred in five patients. Once a patient survived 36 months after the operation, the prognosis was excellent.", "contents": "Long-term survival following aortic valve replacement. Study was made of 95 survivors of aortic valve replacement during the early years of this procedure (1964 to 1970). The average follow-up time was 50.2 months. Survival was not related to hemodynamic parameters, such as cardiac index or left ventricular pressure, and did not appear to be influenced by the type of preoperative valve lesion. A history of angina pectoris and a New York Heart Association Class IV grouping were associated with shorter survival. Associated coronary artery disease was a leading cause of death in those patients surviving less than 2 years and angina pectoris the leading cause of morbidity in the long-term survivors. Sudden death occurred in five patients. Once a patient survived 36 months after the operation, the prognosis was excellent."} {"id": "PMID:1258730", "title": "Diagnosis of Bj\u00f6rk-Shiley aortic valve dysfunction by echocardiography.", "content": "Echocardiography was performed on 26 patients with prosthetic Bj\u00f6rk-Shiley aortic valves (BSAV). Technically satisfactory records were obtained in 22 patients. The systolic displacement of the valve disc varied from 1 to 1.8 cm. (mean, 1.4 cm.). Six patients developed valve dysfunction. Two patients had complete absence of Bj\u00f6rk disc motion and dense echoes in the aortic root were noted on the echocardiogram. Extensive clot formation in and around the valve was seen at operation. After clot removal, these two echocardiograms showed excellent disc motion (1.5 and 1.8 cm.). In a third patient with a clotted valve, marked reduction of the velocity of opening and closing of the valve was noted. Three patients had aortic incompetence without evidence of clot formation. Normal disc motion (DM) was observed in all three. A seventh patient presented with a low output state and markedly reduced valve clicks. Echocardiography revealed normal DM with marked dilatation of the left ventricle. These features were confirmed by angiography. We conclude that: (1) satisfactory echocardiograms can be obtained in most patients with BSAV; (2) echocardiography may be a useful method of detecting Bj\u00f6rk valve dysfunction.", "contents": "Diagnosis of Bj\u00f6rk-Shiley aortic valve dysfunction by echocardiography. Echocardiography was performed on 26 patients with prosthetic Bj\u00f6rk-Shiley aortic valves (BSAV). Technically satisfactory records were obtained in 22 patients. The systolic displacement of the valve disc varied from 1 to 1.8 cm. (mean, 1.4 cm.). Six patients developed valve dysfunction. Two patients had complete absence of Bj\u00f6rk disc motion and dense echoes in the aortic root were noted on the echocardiogram. Extensive clot formation in and around the valve was seen at operation. After clot removal, these two echocardiograms showed excellent disc motion (1.5 and 1.8 cm.). In a third patient with a clotted valve, marked reduction of the velocity of opening and closing of the valve was noted. Three patients had aortic incompetence without evidence of clot formation. Normal disc motion (DM) was observed in all three. A seventh patient presented with a low output state and markedly reduced valve clicks. Echocardiography revealed normal DM with marked dilatation of the left ventricle. These features were confirmed by angiography. We conclude that: (1) satisfactory echocardiograms can be obtained in most patients with BSAV; (2) echocardiography may be a useful method of detecting Bj\u00f6rk valve dysfunction."} {"id": "PMID:1258731", "title": "Dopamine effects on the intestinal circulation.", "content": "The effects of intra-arterial infusion of dopamine on superior mesenteric artery blood flow, intestinal flow, intestinal oxygen consumption, and capillary density were studied in anesthetized dogs before and after blockade of dopamine receptors with haloperidol and after beta-adrenergic receptor blockade with propranolol. Mesenteric blood flow to a distal segment of the small intestine was measured with an electromagnetic blood flow-meter and intestinal oxygen consumption was calculated from the measured arteriovenous oxygen difference across the intestine and total blood flow. Intestinal capillary density was estimated from the clearance of 86Rb. In normal animals prior to dopaminergic or beta-adrenergic blockade, dopamine caused a dose-related decrease in mesenteric blood flow, intestinal oxygen consumption, and 86Rb clearance. Only the lowest dose of the drug, 1 mug/Kg.-min., did not significantly change the intestinal capillary density. In dogs pretreated with the dopamine receptor, antogonist, haloperidol, dopamine (20 mug/Kg.-min.) caused a significant increase in blood flow and oxygen consumption and did not significantly alter the number of perfused intestinal capillaries. These increases in haloperidol-blocked animals administered dopamine were reversed by propranolol. Our results indicate that dopamine caused smooth muscle contraction in mesenteric arterioles and precapillary sphincters, thereby producing intestinal ischemia and hypoxia. These findings with haloperidol and propranolol indicate that dopamine stimulates at least two different receptors in the canine mesenteric vascular bed: a constrictor receptor blocked by haloperidol and a dilator receptor blocked by propranolol.", "contents": "Dopamine effects on the intestinal circulation. The effects of intra-arterial infusion of dopamine on superior mesenteric artery blood flow, intestinal flow, intestinal oxygen consumption, and capillary density were studied in anesthetized dogs before and after blockade of dopamine receptors with haloperidol and after beta-adrenergic receptor blockade with propranolol. Mesenteric blood flow to a distal segment of the small intestine was measured with an electromagnetic blood flow-meter and intestinal oxygen consumption was calculated from the measured arteriovenous oxygen difference across the intestine and total blood flow. Intestinal capillary density was estimated from the clearance of 86Rb. In normal animals prior to dopaminergic or beta-adrenergic blockade, dopamine caused a dose-related decrease in mesenteric blood flow, intestinal oxygen consumption, and 86Rb clearance. Only the lowest dose of the drug, 1 mug/Kg.-min., did not significantly change the intestinal capillary density. In dogs pretreated with the dopamine receptor, antogonist, haloperidol, dopamine (20 mug/Kg.-min.) caused a significant increase in blood flow and oxygen consumption and did not significantly alter the number of perfused intestinal capillaries. These increases in haloperidol-blocked animals administered dopamine were reversed by propranolol. Our results indicate that dopamine caused smooth muscle contraction in mesenteric arterioles and precapillary sphincters, thereby producing intestinal ischemia and hypoxia. These findings with haloperidol and propranolol indicate that dopamine stimulates at least two different receptors in the canine mesenteric vascular bed: a constrictor receptor blocked by haloperidol and a dilator receptor blocked by propranolol."} {"id": "PMID:1258732", "title": "Sinus slowing produced by intracoronary arterial injections of hyperosmotic solutions in man.", "content": "The effect of intracoronary arterial injections of normal saline, contrast agent, hyperosmotic glucose, and mannitol solutions on the sinus rate was studied in 18 patients. Sinus slowing was not produced by isosmotic saline (0.3 Osm. per kilogram of water) when injected into either coronary artery, whereas 76% Urografin (1.9 Osm. per kilogram of water), 20% glucose (1.3 Osm. per kilogram of water), and mannitol (1.2 Osm. per kilogram of water) decreased the sinus rate significantly (P less than 0.001). Among these solutions, Urografin with the highest osmolality produced the most marked sinus slowing, whereas no significant difference was detected between change in the sinus rate with hyperosmotic glucose and mannitol solutions (P greater than 0.5). Moreover, there was no significant difference between the degree of sinus slowing produced by intracoronary injections into the coronary artery of the side which the sinus node artery originated from and the slowing produced by contralateral injections with hyperosmotic solutions (P greater than 0.2). Therefore, it seems unlikely that this sinus slowing would be a result of a direct action on the sinus node including hypoxia and elevated perfusion pressure. Reflex-mediated parasympathetic stimulation may be operative.", "contents": "Sinus slowing produced by intracoronary arterial injections of hyperosmotic solutions in man. The effect of intracoronary arterial injections of normal saline, contrast agent, hyperosmotic glucose, and mannitol solutions on the sinus rate was studied in 18 patients. Sinus slowing was not produced by isosmotic saline (0.3 Osm. per kilogram of water) when injected into either coronary artery, whereas 76% Urografin (1.9 Osm. per kilogram of water), 20% glucose (1.3 Osm. per kilogram of water), and mannitol (1.2 Osm. per kilogram of water) decreased the sinus rate significantly (P less than 0.001). Among these solutions, Urografin with the highest osmolality produced the most marked sinus slowing, whereas no significant difference was detected between change in the sinus rate with hyperosmotic glucose and mannitol solutions (P greater than 0.5). Moreover, there was no significant difference between the degree of sinus slowing produced by intracoronary injections into the coronary artery of the side which the sinus node artery originated from and the slowing produced by contralateral injections with hyperosmotic solutions (P greater than 0.2). Therefore, it seems unlikely that this sinus slowing would be a result of a direct action on the sinus node including hypoxia and elevated perfusion pressure. Reflex-mediated parasympathetic stimulation may be operative."} {"id": "PMID:1258733", "title": "An inexpensive receiver for ECG telemetry.", "content": "A simple, inexpensive ECG demodulator circuit has been described which may be used in conjunction with an ECG telephone transmitter, telephone amplifier, and ECG recorder to form a telemetry system capable of ECG monitoring.", "contents": "An inexpensive receiver for ECG telemetry. A simple, inexpensive ECG demodulator circuit has been described which may be used in conjunction with an ECG telephone transmitter, telephone amplifier, and ECG recorder to form a telemetry system capable of ECG monitoring."} {"id": "PMID:1258734", "title": "Artifacts in portable electrocardiographic monitoring.", "content": "The development of portable ECG monitoring techniques has brought with it new insights into the electrical activity of the heart, and new problems in interpretation of artifacts. This article summarizes and classifies 15 different types of artifacts observed from dynamic electrocardiography. The artifacts appear partly as pseudo-arrhythmias mimicking supraventricular, ventricular, junctional, and dissociative rhythms. There are also non-arrhythmic artifacts which can be misleading in the interpretation of Q-waves, S-T-segments, and T-waves. Eight of the 15 artifacts have potentially serious consequences if not understood, and in 2 instances an artifact almost led to the unnecessary implantation of an artificial cardiac pacemaker.", "contents": "Artifacts in portable electrocardiographic monitoring. The development of portable ECG monitoring techniques has brought with it new insights into the electrical activity of the heart, and new problems in interpretation of artifacts. This article summarizes and classifies 15 different types of artifacts observed from dynamic electrocardiography. The artifacts appear partly as pseudo-arrhythmias mimicking supraventricular, ventricular, junctional, and dissociative rhythms. There are also non-arrhythmic artifacts which can be misleading in the interpretation of Q-waves, S-T-segments, and T-waves. Eight of the 15 artifacts have potentially serious consequences if not understood, and in 2 instances an artifact almost led to the unnecessary implantation of an artificial cardiac pacemaker."} {"id": "PMID:1258735", "title": "Systolic time intervals in induced atrial fibrillation in the dog.", "content": "The effect of induced atrial fibrillation on ventricular performance in the dog as measured by changes in the systolic time intervals (STI), was investigated. Atrial fibrillation was induced by enhancement of vagal tone with morphine sulfate, followed by direct mechanical stimulation of the atrium. Dogs received 15 mg. per kilogram of morphine sulfate subcutaneously, followed by 3 mg. per kilogram of pentobarbital sodium. ECG, atrial electrogram, phonocardiogram, and direct arterial blood pressure were recorded during periods of sinus rhythm and during periods of induced atrial fibrillation. Data were analyzed by selecting 20 representative cardiac cycles from each condition in each of 15 dogs. Cycles were selected so that the broadest spectrum of rates was examined for each animal. Three hundred cycles were examined from each condition, or a total of 600 cycles. Heart rate (HR), left ventricular end-diastolic pressure, and aortic end-diastolic pressure were unchanged during atrial fibrillation. The left ventricular pre-ejection period (LVPEP), externally derived isovolumic contraction time (EICT), and total mechanical systole (S1-S2 interval) were all found to increase significantly in duration after the induction of atrial fibrillation. The left ventricular ejection time (LVET) and the electromechanical delay (Q-S1 interval) were significantly decreased in duration following the induction of atrial fibrillation.", "contents": "Systolic time intervals in induced atrial fibrillation in the dog. The effect of induced atrial fibrillation on ventricular performance in the dog as measured by changes in the systolic time intervals (STI), was investigated. Atrial fibrillation was induced by enhancement of vagal tone with morphine sulfate, followed by direct mechanical stimulation of the atrium. Dogs received 15 mg. per kilogram of morphine sulfate subcutaneously, followed by 3 mg. per kilogram of pentobarbital sodium. ECG, atrial electrogram, phonocardiogram, and direct arterial blood pressure were recorded during periods of sinus rhythm and during periods of induced atrial fibrillation. Data were analyzed by selecting 20 representative cardiac cycles from each condition in each of 15 dogs. Cycles were selected so that the broadest spectrum of rates was examined for each animal. Three hundred cycles were examined from each condition, or a total of 600 cycles. Heart rate (HR), left ventricular end-diastolic pressure, and aortic end-diastolic pressure were unchanged during atrial fibrillation. The left ventricular pre-ejection period (LVPEP), externally derived isovolumic contraction time (EICT), and total mechanical systole (S1-S2 interval) were all found to increase significantly in duration after the induction of atrial fibrillation. The left ventricular ejection time (LVET) and the electromechanical delay (Q-S1 interval) were significantly decreased in duration following the induction of atrial fibrillation."} {"id": "PMID:1258736", "title": "Acute myocardial infarction following wasp sting. Report of two cases and critical survey of the literature.", "content": "Over the span of two or three days in August, 1972, in two separate communities in eastern Massachusetts two men, one aged 39, the other 66, each without previous overt heart disease, were stung by wasps. Each went into shock rapidly after an interval of over a half-hour developed chest pain and, later, sequential electrocardiographic changes diagnostic of acute myocardial infarction. Each survived; each had normal electrocardiograms before the sting. Though preexistent coronary artery disease can be excluded in neither, the view is favored that acute myocardial infarction in each was caused by deficient coronary perfusion secondary to anaphylactic shock induced by the wasp stings. An intriguing case was just recently reported58 of a 62-year-old man with previous angina who developed pulmonary edema but no chest pain following wasp sting and went on to show rapidly reversed electrocardiographic changes attributable to subendocardial ischemia or infarction. In a sense, this sequence fills the gap as an intermediate phase between the normal and the two individuals described here who developed pain after anaphylactic shock, then proceeded, perhaps through this phase, to develop transmural infarction.", "contents": "Acute myocardial infarction following wasp sting. Report of two cases and critical survey of the literature. Over the span of two or three days in August, 1972, in two separate communities in eastern Massachusetts two men, one aged 39, the other 66, each without previous overt heart disease, were stung by wasps. Each went into shock rapidly after an interval of over a half-hour developed chest pain and, later, sequential electrocardiographic changes diagnostic of acute myocardial infarction. Each survived; each had normal electrocardiograms before the sting. Though preexistent coronary artery disease can be excluded in neither, the view is favored that acute myocardial infarction in each was caused by deficient coronary perfusion secondary to anaphylactic shock induced by the wasp stings. An intriguing case was just recently reported58 of a 62-year-old man with previous angina who developed pulmonary edema but no chest pain following wasp sting and went on to show rapidly reversed electrocardiographic changes attributable to subendocardial ischemia or infarction. In a sense, this sequence fills the gap as an intermediate phase between the normal and the two individuals described here who developed pain after anaphylactic shock, then proceeded, perhaps through this phase, to develop transmural infarction."} {"id": "PMID:1258747", "title": "Primary risk factors in patients with myocardial infarction.", "content": "A predicted probability of suffering myocardial infarction based on a multiple risk function involving serum cholesterol, systolic blood pressure, and tobacco consumption, was allocated retrospectively to 270 men who survived a primary myocardial infarction. The infarction patients were representative of all surviving, diagnosed cases of primary infarction in men in certain age groups in G\u00f6teborg, Sweden, during the years 1968-70. The patients were divided into three groups-low, moderate, and high risk. A large number of patients had suffered infarction despite relatively low risk, but the patients showed a tendency toward higher risk in comparison with the risk distribution in a representative population sample. In order to study whether other variables, not included in the risk function, could \"explain\" the infarction in patients with relatiely low risk, the different risk groups were compared. A high degree of mental stress, diabetes mellitus, and dyspnea on exertion, and possibly also raised triglycerides, contributed to \"explain\" the infarctions in the low-risk group. Low physical activity during leisure time was probably also of importance.", "contents": "Primary risk factors in patients with myocardial infarction. A predicted probability of suffering myocardial infarction based on a multiple risk function involving serum cholesterol, systolic blood pressure, and tobacco consumption, was allocated retrospectively to 270 men who survived a primary myocardial infarction. The infarction patients were representative of all surviving, diagnosed cases of primary infarction in men in certain age groups in G\u00f6teborg, Sweden, during the years 1968-70. The patients were divided into three groups-low, moderate, and high risk. A large number of patients had suffered infarction despite relatively low risk, but the patients showed a tendency toward higher risk in comparison with the risk distribution in a representative population sample. In order to study whether other variables, not included in the risk function, could \"explain\" the infarction in patients with relatiely low risk, the different risk groups were compared. A high degree of mental stress, diabetes mellitus, and dyspnea on exertion, and possibly also raised triglycerides, contributed to \"explain\" the infarctions in the low-risk group. Low physical activity during leisure time was probably also of importance."} {"id": "PMID:1258748", "title": "The ECG of constrictive pericarditis--pattern resembling right ventricular hypertrophy.", "content": "The ECG changes in 122 cases of constrictive pericarditis have been reviewed. Ninety-five per cent of tracings were typical and showed a normal QRS axis, low voltage, and generalized T wave flattening or inversion. The remaining six tracings showed evidence of right ventricular hypertrophy and half of these showed right axis deviation in addition. In only one could these findings be readily accounted for by the presence of severe fibrotic annular subpulmonic constriction; the remainder are unexplained and it is postulated that cardiac rotation and distrotion is causative since none of the other mechanisms of right axis deviation or right ventricular hypertrophy were operative.", "contents": "The ECG of constrictive pericarditis--pattern resembling right ventricular hypertrophy. The ECG changes in 122 cases of constrictive pericarditis have been reviewed. Ninety-five per cent of tracings were typical and showed a normal QRS axis, low voltage, and generalized T wave flattening or inversion. The remaining six tracings showed evidence of right ventricular hypertrophy and half of these showed right axis deviation in addition. In only one could these findings be readily accounted for by the presence of severe fibrotic annular subpulmonic constriction; the remainder are unexplained and it is postulated that cardiac rotation and distrotion is causative since none of the other mechanisms of right axis deviation or right ventricular hypertrophy were operative."} {"id": "PMID:1258749", "title": "The effect of vitamin E on platelet aggregation.", "content": "Platelet aggregation studies were performed in five men with coronary artery disease and angina pectoris and five men with nonspecific chest pain before and after receiving 1,000 I.U. of alpha-tocopherol acetate orally per day for 8 days. There was no significant difference in the platelet aggregation response to three concentrations of ADP and two concentrations of epinephrine between the pre- and post-vitamin E periods among the 10 patients. If tocopherol acetate (vitamin E) has any beneficial effect on the prevention of thromboemolism or in the treatment of angina pectoris and peripheral vascular disease, it is not via inhibition of platelet aggregation.", "contents": "The effect of vitamin E on platelet aggregation. Platelet aggregation studies were performed in five men with coronary artery disease and angina pectoris and five men with nonspecific chest pain before and after receiving 1,000 I.U. of alpha-tocopherol acetate orally per day for 8 days. There was no significant difference in the platelet aggregation response to three concentrations of ADP and two concentrations of epinephrine between the pre- and post-vitamin E periods among the 10 patients. If tocopherol acetate (vitamin E) has any beneficial effect on the prevention of thromboemolism or in the treatment of angina pectoris and peripheral vascular disease, it is not via inhibition of platelet aggregation."} {"id": "PMID:1258750", "title": "A controlled trial of intramuscular lidocaine in the prevention of premature ventricular contractions associated with acute myocardial infarction.", "content": "Intramuscular lidocaine administration is known to produce blood concentration levels considered to be therapeutic for prevention of premature ventricular contractions. This double blind study was designed to study the effect of intramuscular lidocaine in the prevention of PVC's in acute myocardial infarction. Forty-six patients with confirmed acute myocardial infarction, without congestive heart failure, shock, or major arrhythmias were admitted to the trial. Twenty-one patients received 4.5 mg. per kilogram of intramuscular lidocaine and 25 patients received placebo in the deltoid muscle within 14 hours of the onset of symptoms. Rhythm strips of 2 minutes' duration, blood pressure, heart rate, and blood specimens for blood concentration levels were obtained prior to and 5, 10, 15, 30, 60, 90, and 120 minutes after injection. The mean blood concentration level of lidocaine was 1.81 +/- 0.22 mug per milliliter at 5 minutes, reached a maximum of 2.18 +/- 0.22 mug per milliliter at 10 minutes, and was still 0.81 +/- 0.05 at 120 minutes. Analysis of rhythm strips revealed that only three of 21 patients (14 per cent) in the intramuscular lidocaine group developed at least one PVC as compared to 13 of 25 (52 per cent) in the placebo group (p less than 0.0005). No significant toxic effects were noted. This study suggests that intramuscular lidocaine may significantly reduce potentially fatal arrhythmias in early phases of acute myocardial infarction.", "contents": "A controlled trial of intramuscular lidocaine in the prevention of premature ventricular contractions associated with acute myocardial infarction. Intramuscular lidocaine administration is known to produce blood concentration levels considered to be therapeutic for prevention of premature ventricular contractions. This double blind study was designed to study the effect of intramuscular lidocaine in the prevention of PVC's in acute myocardial infarction. Forty-six patients with confirmed acute myocardial infarction, without congestive heart failure, shock, or major arrhythmias were admitted to the trial. Twenty-one patients received 4.5 mg. per kilogram of intramuscular lidocaine and 25 patients received placebo in the deltoid muscle within 14 hours of the onset of symptoms. Rhythm strips of 2 minutes' duration, blood pressure, heart rate, and blood specimens for blood concentration levels were obtained prior to and 5, 10, 15, 30, 60, 90, and 120 minutes after injection. The mean blood concentration level of lidocaine was 1.81 +/- 0.22 mug per milliliter at 5 minutes, reached a maximum of 2.18 +/- 0.22 mug per milliliter at 10 minutes, and was still 0.81 +/- 0.05 at 120 minutes. Analysis of rhythm strips revealed that only three of 21 patients (14 per cent) in the intramuscular lidocaine group developed at least one PVC as compared to 13 of 25 (52 per cent) in the placebo group (p less than 0.0005). No significant toxic effects were noted. This study suggests that intramuscular lidocaine may significantly reduce potentially fatal arrhythmias in early phases of acute myocardial infarction."} {"id": "PMID:1258751", "title": "The localization of coronary artery stenoses by 12 lead ECG response to graded exercise test: support for intercoronary steal.", "content": "In 39 consecutive patients with unequivocally positive postexercise ECG we have correlated the location and severity of the coronary artery stenoses with the ECG leads in which ischemic ST changes occured. Patients with major stenoses of the right coronary artery, with or without disease of the left coronary system, showed ischemic ST changes in Leads II, III, and aVF. Patients with major stenoses of the left coronary system, many of whom had suffered old inferior wall infarction, showed ST changes in Leads I, aVL, and the chest leads. A group of 11 patients showed ischemic ST changes in leads other than those expected on the basis of the location and severity of coronary artery stenoses. In each of these 11 patients large collateral channels were donated by the vessel in whose territory the ischemic changes occurred. This finding lends support to the concept of intercoronary \"steal\" during exercise in coronary artery disease, at the same time reducing the value of the postexercise 12 lead ECG in predicting the location and severity of coronary artery stenoses.", "contents": "The localization of coronary artery stenoses by 12 lead ECG response to graded exercise test: support for intercoronary steal. In 39 consecutive patients with unequivocally positive postexercise ECG we have correlated the location and severity of the coronary artery stenoses with the ECG leads in which ischemic ST changes occured. Patients with major stenoses of the right coronary artery, with or without disease of the left coronary system, showed ischemic ST changes in Leads II, III, and aVF. Patients with major stenoses of the left coronary system, many of whom had suffered old inferior wall infarction, showed ST changes in Leads I, aVL, and the chest leads. A group of 11 patients showed ischemic ST changes in leads other than those expected on the basis of the location and severity of coronary artery stenoses. In each of these 11 patients large collateral channels were donated by the vessel in whose territory the ischemic changes occurred. This finding lends support to the concept of intercoronary \"steal\" during exercise in coronary artery disease, at the same time reducing the value of the postexercise 12 lead ECG in predicting the location and severity of coronary artery stenoses."} {"id": "PMID:1258752", "title": "Long-term survival of elderly patients after pacemaker implatation.", "content": "The follow-up of 80 patients above the age of 70 years with implanted pacemakers is described. These patients were the most advanced in age from a total group of 150 with implanted pacemakers. Their ages ranged from 70 to 87 years, with an average of 75.4 years; 50 were male and 30 were female. An epicardial electrode was implanted in 13 patients and an endocardial electrode in 67. The pacemaker was implanted in 76 patients for symptomatic atrioventricular block and in four patients for sick-sinus syndrome. Two patients (2.5 per cent) died during the postoperative period and 19 patients within a period of 3 months to 6 years after the implantation. The survival rates were: 1 year, 90.0 per cent; 2 years, 82.1 per cent; 3 years, 74.1 per cent; 4 years, 67.2 per cent; 5 years, 58.3 percent. These survival rates were surprisingly similar, for the first 3 years of follow-up, to those of our and others' previous studies, which included all age groups. The survival rates in the most advanced age groups decreased in comparison only in fourth and fifth years after the implantation. There was no evidence of new episodes of myocardial infarction among this group of patients during the follow-up period. We conclude that even in patients of the most advanced age groups the implantation of an endocardial pacemaker significantly prolongs life, improves its quality, and this at a low operative risk.", "contents": "Long-term survival of elderly patients after pacemaker implatation. The follow-up of 80 patients above the age of 70 years with implanted pacemakers is described. These patients were the most advanced in age from a total group of 150 with implanted pacemakers. Their ages ranged from 70 to 87 years, with an average of 75.4 years; 50 were male and 30 were female. An epicardial electrode was implanted in 13 patients and an endocardial electrode in 67. The pacemaker was implanted in 76 patients for symptomatic atrioventricular block and in four patients for sick-sinus syndrome. Two patients (2.5 per cent) died during the postoperative period and 19 patients within a period of 3 months to 6 years after the implantation. The survival rates were: 1 year, 90.0 per cent; 2 years, 82.1 per cent; 3 years, 74.1 per cent; 4 years, 67.2 per cent; 5 years, 58.3 percent. These survival rates were surprisingly similar, for the first 3 years of follow-up, to those of our and others' previous studies, which included all age groups. The survival rates in the most advanced age groups decreased in comparison only in fourth and fifth years after the implantation. There was no evidence of new episodes of myocardial infarction among this group of patients during the follow-up period. We conclude that even in patients of the most advanced age groups the implantation of an endocardial pacemaker significantly prolongs life, improves its quality, and this at a low operative risk."} {"id": "PMID:1258755", "title": "Facilitation of A-V nodal reciprocation by procainamide.", "content": "Procainamide is known to depress conduction through the A-V node, and this property may facilitate the development of ventricular reciprocal beats or echoes. The occurrence of ventricular reciprocal beats was studied in 20 open-chest dogs before and after the administration of procainamide. While the ventricle was paced by basic stimuli, early ventricular premature beats were introduced at various coupling intervals to induce ventricular echoes. When ventricular echoes could be induced in a given heart, there was a continuous range of coupling intervals (or echo zone) within which ventricular echoes occurred. In the control state, no echo occurred in eight dogs and the echoes developed in 12 dogs with the mean echo zone of 38.3 msec. The effect of procainamide was studied at its therapeutic blood levels about 25 minutes after an intravenous injection of the drug in a dose of 10 mg. per kilogram. Of the first group of eight dogs, in which no echo occurred in the control state, four dogs developed ventricular echoes after the administration of procainamide with the mean echo zone of 29.3 msec. for the group. Of the second group of 12 dogs, in which ventricular echoes were induced in the control state, the administration of procainamide increased the echo zone in 10 dogs with the mean echo zone of 67.8 msec. for the group. Ventricular reciprocal beats were often sustained to produce short runs of supraventricular tachycardia in five dogs after the administration of procainamide. The results demonstrated a potentially deleterious effect of procainamide in facilitating the inducation of A-V nodal reciprocation by closely coupled ventricular premature beats.", "contents": "Facilitation of A-V nodal reciprocation by procainamide. Procainamide is known to depress conduction through the A-V node, and this property may facilitate the development of ventricular reciprocal beats or echoes. The occurrence of ventricular reciprocal beats was studied in 20 open-chest dogs before and after the administration of procainamide. While the ventricle was paced by basic stimuli, early ventricular premature beats were introduced at various coupling intervals to induce ventricular echoes. When ventricular echoes could be induced in a given heart, there was a continuous range of coupling intervals (or echo zone) within which ventricular echoes occurred. In the control state, no echo occurred in eight dogs and the echoes developed in 12 dogs with the mean echo zone of 38.3 msec. The effect of procainamide was studied at its therapeutic blood levels about 25 minutes after an intravenous injection of the drug in a dose of 10 mg. per kilogram. Of the first group of eight dogs, in which no echo occurred in the control state, four dogs developed ventricular echoes after the administration of procainamide with the mean echo zone of 29.3 msec. for the group. Of the second group of 12 dogs, in which ventricular echoes were induced in the control state, the administration of procainamide increased the echo zone in 10 dogs with the mean echo zone of 67.8 msec. for the group. Ventricular reciprocal beats were often sustained to produce short runs of supraventricular tachycardia in five dogs after the administration of procainamide. The results demonstrated a potentially deleterious effect of procainamide in facilitating the inducation of A-V nodal reciprocation by closely coupled ventricular premature beats."} {"id": "PMID:1258756", "title": "The effects of acetylstrophanthidin on the response of the AV junction to adrenergic stimulation studied in dogs.", "content": "The response of the AV junction to adrenergic stimulation was studied in 35 anesthetized open-chest dogs before and after the injection of acetylstrophanthidin (5mug) directly into the AV node artery. An AV junctional rhythm was obtained under control conditions by injecting norepinephrine (n = 9) or isoproterenol (n = 8) into the AV node artery and by stimulation of the left stellate ganglion (n = 11) after selectively injecting propranolol into the sinus node artery. Acetylstrophanthidin brought about various degrees of conduction block from simple PR interval prolongation to complete heart block, and decreased the chronotropic response of the AV junction to adrenergic stimulation. In seven animals the appearance of a spontaneous second degree AV block did not reduce the AV junctional response to adrenergic stimulation. Acetylstrophanthidin also reduced the ventricular acceleration produced by adrenergic stimulation during atrial fibrillation. These results suggest that the anti-adrenergic effect of cardiac glycosides may not only be involved in the mechanism of AV conduction disturbances during digitalis intoxication, but may also play a role in slowing the ventricular rate during atrial fibrillation.", "contents": "The effects of acetylstrophanthidin on the response of the AV junction to adrenergic stimulation studied in dogs. The response of the AV junction to adrenergic stimulation was studied in 35 anesthetized open-chest dogs before and after the injection of acetylstrophanthidin (5mug) directly into the AV node artery. An AV junctional rhythm was obtained under control conditions by injecting norepinephrine (n = 9) or isoproterenol (n = 8) into the AV node artery and by stimulation of the left stellate ganglion (n = 11) after selectively injecting propranolol into the sinus node artery. Acetylstrophanthidin brought about various degrees of conduction block from simple PR interval prolongation to complete heart block, and decreased the chronotropic response of the AV junction to adrenergic stimulation. In seven animals the appearance of a spontaneous second degree AV block did not reduce the AV junctional response to adrenergic stimulation. Acetylstrophanthidin also reduced the ventricular acceleration produced by adrenergic stimulation during atrial fibrillation. These results suggest that the anti-adrenergic effect of cardiac glycosides may not only be involved in the mechanism of AV conduction disturbances during digitalis intoxication, but may also play a role in slowing the ventricular rate during atrial fibrillation."} {"id": "PMID:1258757", "title": "Atrial T (Ta) loop in patients with A-V block: a trial to differentiate normal and abnoral groups.", "content": "The P and the Ta waves were recorded with high fidelity and high amplification. The P and the Ta loops were constructed from these waves. Human subjects with A-V block were used, so that the Ta waves could be completely visualized. Subjects were separated into two groups: one group with minimal clinical evidence of heart disease and another with more severe disease. There were great and important differences in the Ta loops between the two groups with minimal differences in the P loops. In the patients with minimal heart disease, the Ta loop was always oriented to the right and superiorly. The P-Ta angle was approximately 180 degrees and all patients in this group showed a small spatial atrial gradient oriented to the left and inferiorly. These findings are similar to those found in normal dogs reported separately in the Journal. In the group of four patients with more severe heart disease, the P-Ta angle varied widely and deviated greatly form 180 degree. The satial atrial gradient was very large in three cases. The findings and others such as the direction of the maximum Ta vectors were diagnostically useful in separating the Ta loops of the two patient groups. Results indicate that the Ta loop may be very useful in separating normal from diseased atria in individuals with A-V block. There are some frequency differences between the Ta wave and the QRS complex. If the Ta wave could be extracted from the QRS complex by the use of some kind of filter when A-V block dose not exist, most of the Ta wave could be visualized. This, along with high fidelity recording techniques, may help detect atrial abnormalities in patients without A-V block. Future development of this equipment as a clinical tool is hoped for.", "contents": "Atrial T (Ta) loop in patients with A-V block: a trial to differentiate normal and abnoral groups. The P and the Ta waves were recorded with high fidelity and high amplification. The P and the Ta loops were constructed from these waves. Human subjects with A-V block were used, so that the Ta waves could be completely visualized. Subjects were separated into two groups: one group with minimal clinical evidence of heart disease and another with more severe disease. There were great and important differences in the Ta loops between the two groups with minimal differences in the P loops. In the patients with minimal heart disease, the Ta loop was always oriented to the right and superiorly. The P-Ta angle was approximately 180 degrees and all patients in this group showed a small spatial atrial gradient oriented to the left and inferiorly. These findings are similar to those found in normal dogs reported separately in the Journal. In the group of four patients with more severe heart disease, the P-Ta angle varied widely and deviated greatly form 180 degree. The satial atrial gradient was very large in three cases. The findings and others such as the direction of the maximum Ta vectors were diagnostically useful in separating the Ta loops of the two patient groups. Results indicate that the Ta loop may be very useful in separating normal from diseased atria in individuals with A-V block. There are some frequency differences between the Ta wave and the QRS complex. If the Ta wave could be extracted from the QRS complex by the use of some kind of filter when A-V block dose not exist, most of the Ta wave could be visualized. This, along with high fidelity recording techniques, may help detect atrial abnormalities in patients without A-V block. Future development of this equipment as a clinical tool is hoped for."} {"id": "PMID:1258758", "title": "Coronary artery spasm as the cause of myocardial infarction during coronary arteriogarphy.", "content": "Catheter-induced coronary artery spasm has been observed frequently. It is usually transient, reacts to the administration of nitroglycerin, and its distribution is generally confined to an area in proximity ot the intubated catheter. A 43-year-old woman with recurrent chest pain was found to have a rather long segment of tight proximal obstruction of the right coronary artery and experienced a myocardial infarction during coronary catheterization. Because of recurrent attacks of severe chest pain, coronary artery bypass surgery was performed which failed to result in significant improvement of her symptoms. Two repeat coronary cineangiograms seven weeks and three years after surgery revealed the proximal right coronary artery to be free of stenotic lesions or of luminal irregularities. After considering possible mechanisms of myocardial necrosis in the presence of normal coronary arteries it is concluded that myocardial necrosis can result from catheter-induced coronary artery spasm in spite of administration of nitroglycerin.", "contents": "Coronary artery spasm as the cause of myocardial infarction during coronary arteriogarphy. Catheter-induced coronary artery spasm has been observed frequently. It is usually transient, reacts to the administration of nitroglycerin, and its distribution is generally confined to an area in proximity ot the intubated catheter. A 43-year-old woman with recurrent chest pain was found to have a rather long segment of tight proximal obstruction of the right coronary artery and experienced a myocardial infarction during coronary catheterization. Because of recurrent attacks of severe chest pain, coronary artery bypass surgery was performed which failed to result in significant improvement of her symptoms. Two repeat coronary cineangiograms seven weeks and three years after surgery revealed the proximal right coronary artery to be free of stenotic lesions or of luminal irregularities. After considering possible mechanisms of myocardial necrosis in the presence of normal coronary arteries it is concluded that myocardial necrosis can result from catheter-induced coronary artery spasm in spite of administration of nitroglycerin."} {"id": "PMID:1258759", "title": "Spectrum of sinus node dysfunction in two siblings.", "content": "Two siblings, ages 14 and 23, with various features of sinus node dysfunction have been reported. Sinus bradycardia was the presenting feature in both patients. During the follow-up period both patients developed various types of ectopic rhythms which increased with exercise. One of them developed \"silent atrium\" at the age of 23 and had cerebral embolus as a complication. The other patient had frequent syncopal episodes and had to be treated with a combination of electronic pacemaker and antiarrhythmic drugs.", "contents": "Spectrum of sinus node dysfunction in two siblings. Two siblings, ages 14 and 23, with various features of sinus node dysfunction have been reported. Sinus bradycardia was the presenting feature in both patients. During the follow-up period both patients developed various types of ectopic rhythms which increased with exercise. One of them developed \"silent atrium\" at the age of 23 and had cerebral embolus as a complication. The other patient had frequent syncopal episodes and had to be treated with a combination of electronic pacemaker and antiarrhythmic drugs."} {"id": "PMID:1258768", "title": "Functional significance of coronary collateral vessels in patients with acute myocardial infarction: relation to pump performance, cardiogenic shock and survival.", "content": "In 20 patients with acute myocardial infarction requiring emergency left heart catheterization and coronary arteriography, ventricular function and clinical course were related to collateral vessels supplying the infarcted area. The major coronary artery to the infarcted region was severely obstructed in all patients. Patients with adequate collateral vessels (Group I, no. = 6) and those with no or inadequate collateral channels (Group II, no. = 14) had similar findings with respect to age, site of infarction, prevalence of prior infarction and presence of multivessel disease. However, there were significant differences between Groups I and II in left ventricular end-diastolic pressure (13 versus 30 mm Hg), cardiac index (3.05 versus 2.04 liters/min per m2), stroke work index (45 versus 13 g-m/m2), ejection fraction (42 versus 20 percent) and area of dyssynergy (14 versus 47 percent). Moreover, in Group I all patients survived and none had cardiogenic shock, whereas in Group II 10 of 14 patients had shock and 8 of 14 died. The rapidity of vessel obstruction appeared to influence collateralization since infarction was preceded by angina pectoris more frequently in Group I than in Group II. These results indicate that well functioning anastomotic channels to the distal trunk of the blocked coronary artery may afford some protection of pump function and improve the prognosis in acute myocardial infarction.", "contents": "Functional significance of coronary collateral vessels in patients with acute myocardial infarction: relation to pump performance, cardiogenic shock and survival. In 20 patients with acute myocardial infarction requiring emergency left heart catheterization and coronary arteriography, ventricular function and clinical course were related to collateral vessels supplying the infarcted area. The major coronary artery to the infarcted region was severely obstructed in all patients. Patients with adequate collateral vessels (Group I, no. = 6) and those with no or inadequate collateral channels (Group II, no. = 14) had similar findings with respect to age, site of infarction, prevalence of prior infarction and presence of multivessel disease. However, there were significant differences between Groups I and II in left ventricular end-diastolic pressure (13 versus 30 mm Hg), cardiac index (3.05 versus 2.04 liters/min per m2), stroke work index (45 versus 13 g-m/m2), ejection fraction (42 versus 20 percent) and area of dyssynergy (14 versus 47 percent). Moreover, in Group I all patients survived and none had cardiogenic shock, whereas in Group II 10 of 14 patients had shock and 8 of 14 died. The rapidity of vessel obstruction appeared to influence collateralization since infarction was preceded by angina pectoris more frequently in Group I than in Group II. These results indicate that well functioning anastomotic channels to the distal trunk of the blocked coronary artery may afford some protection of pump function and improve the prognosis in acute myocardial infarction."} {"id": "PMID:1258769", "title": "Functional abnormalities in nonoccluded regions of myocardium after experimental coronary occlusion.", "content": "The performance characteristics of both ischemic and \"adjacent\" and \"remote\" nonischemic myocardium were studied in open chest dogs by three mercury-in-Silastic length gauges sutured to the anterior surface of the left ventricle before and after occlusion of the distal left anterior descending coronary artery. The adjacent gauge was separated from the ischemic segment by one large nonoccluded diagonal branch of the left anterior descending artery. Remote myocardium was separated from the ischemic area by two such branches. At the time of occlusion epicardial S-T segment elevation appeared in the ischemic region but not in the adjacent or remote regions. Immediately after occlusion, typical changes of ischemic dysfunction appeared. Late systolic lengthening, depression of systolic shortening and increased diastolic compliance occurred consistently and simultaneously in ischemic and adjacent regions and inconsistently in the remote region. Five minutes after occlusion, fiber shortening was depressed to 21, 58 and 67 percent of control values in ischemic, adjacent and remote regions, respectively. Heart rate did not change, and mean arterial pressure decreased slightly. These changes persisted over time. In 11 of these dogs, end-diastolic pressure was maintained constant 20 minutes after occlusion. Systolic shortening was depressed to 40 and 74 percent of control values in the ischemic and adjacent regions, respectively. In six dogs, end-diastolic pressure was varied form 5 to 20 mm Hg by rapid volume loading during the control state and 30 minutes after occlusion. Systolic shortening in ischemic, adjacent and remote regions was depressed to 20, 40 and 65 percent of control values, respectively. The severity of all functional alterations after coronary occlusion was directly related to proximity to the ischemic region. These results indicate that depression of left ventricular function after coronary occlusion may be partially related to previously unrecognized depression of function in apparently \"nonischemic\" myocardium.", "contents": "Functional abnormalities in nonoccluded regions of myocardium after experimental coronary occlusion. The performance characteristics of both ischemic and \"adjacent\" and \"remote\" nonischemic myocardium were studied in open chest dogs by three mercury-in-Silastic length gauges sutured to the anterior surface of the left ventricle before and after occlusion of the distal left anterior descending coronary artery. The adjacent gauge was separated from the ischemic segment by one large nonoccluded diagonal branch of the left anterior descending artery. Remote myocardium was separated from the ischemic area by two such branches. At the time of occlusion epicardial S-T segment elevation appeared in the ischemic region but not in the adjacent or remote regions. Immediately after occlusion, typical changes of ischemic dysfunction appeared. Late systolic lengthening, depression of systolic shortening and increased diastolic compliance occurred consistently and simultaneously in ischemic and adjacent regions and inconsistently in the remote region. Five minutes after occlusion, fiber shortening was depressed to 21, 58 and 67 percent of control values in ischemic, adjacent and remote regions, respectively. Heart rate did not change, and mean arterial pressure decreased slightly. These changes persisted over time. In 11 of these dogs, end-diastolic pressure was maintained constant 20 minutes after occlusion. Systolic shortening was depressed to 40 and 74 percent of control values in the ischemic and adjacent regions, respectively. In six dogs, end-diastolic pressure was varied form 5 to 20 mm Hg by rapid volume loading during the control state and 30 minutes after occlusion. Systolic shortening in ischemic, adjacent and remote regions was depressed to 20, 40 and 65 percent of control values, respectively. The severity of all functional alterations after coronary occlusion was directly related to proximity to the ischemic region. These results indicate that depression of left ventricular function after coronary occlusion may be partially related to previously unrecognized depression of function in apparently \"nonischemic\" myocardium."} {"id": "PMID:1258770", "title": "Alterations in myocardial function during bacterial infective cardiomyopathy.", "content": "The status of myocardial function in rabbits subjected to cardiac catheterization and infection with Streptococcus viridans was assessed at 3 and 6 days. Sham-operated control animals as well as uninfected catheterized animals were used for comparison. Although left heart hypertrophy and interstitial edema were evident in both uninfected and infected animals, the infected animals exhibited in addition mononuclear cell infiltration and muscle degeneration as well as lung congestion and accumulation of pleural fluid. Both uninfected and infected animals has elevated levels of serum creatine phosphokinase, lactic dehydrogenase and glutamic oxaloacetic transaminase as well as electrocardiographic abnormalities such as increased amplitude of the ORS complex and flattening or inversion of the T wave. Unlike findings in the uninfected animals, the serum calcium, magnesium and sodium levels were slightly but significantly decreased and serum potassium levels were increased in the infected rabbits. Both heart rate and pulse pressure were higher in 6 day uninfected and 3 day infected animals whereas 6 day infected animals showed a decrease in heart rate. In comparison to the sham-operated control rabbits and the uninfected animals, the infected animals exhibited depression in the rates of left ventricular pressure development and relaxation as well as prolongation in time for half relaxation in situ. Relative maximal contractile element velocity extrapolated from intraventricular pressure-velocity curves was decreased by 24, 52 and 76 percent, respectively, of control values in the uninfected hearts and those with 3 and 6 days of infection. The isolated perfused hearts from infected animals also generated less contractile force and showed a decrease in the rates of contraction and relaxation, but half-relaxation time was increased. These results demonstrate myocardial dysfunction during experimental bacterial endocarditis and provide evidence that infective cardiomyopathy is associated with heart failure.", "contents": "Alterations in myocardial function during bacterial infective cardiomyopathy. The status of myocardial function in rabbits subjected to cardiac catheterization and infection with Streptococcus viridans was assessed at 3 and 6 days. Sham-operated control animals as well as uninfected catheterized animals were used for comparison. Although left heart hypertrophy and interstitial edema were evident in both uninfected and infected animals, the infected animals exhibited in addition mononuclear cell infiltration and muscle degeneration as well as lung congestion and accumulation of pleural fluid. Both uninfected and infected animals has elevated levels of serum creatine phosphokinase, lactic dehydrogenase and glutamic oxaloacetic transaminase as well as electrocardiographic abnormalities such as increased amplitude of the ORS complex and flattening or inversion of the T wave. Unlike findings in the uninfected animals, the serum calcium, magnesium and sodium levels were slightly but significantly decreased and serum potassium levels were increased in the infected rabbits. Both heart rate and pulse pressure were higher in 6 day uninfected and 3 day infected animals whereas 6 day infected animals showed a decrease in heart rate. In comparison to the sham-operated control rabbits and the uninfected animals, the infected animals exhibited depression in the rates of left ventricular pressure development and relaxation as well as prolongation in time for half relaxation in situ. Relative maximal contractile element velocity extrapolated from intraventricular pressure-velocity curves was decreased by 24, 52 and 76 percent, respectively, of control values in the uninfected hearts and those with 3 and 6 days of infection. The isolated perfused hearts from infected animals also generated less contractile force and showed a decrease in the rates of contraction and relaxation, but half-relaxation time was increased. These results demonstrate myocardial dysfunction during experimental bacterial endocarditis and provide evidence that infective cardiomyopathy is associated with heart failure."} {"id": "PMID:1258771", "title": "\"Agenesis\" of ductus arteriosus associated with the syndrome of tetralogy of Fallot and absent pulmonary valve.", "content": "Four infants with the severe form of the syndrome of tetralogy of Fallot and absent pulmonary valve are described. All had severe respiratory distress due to bronchial compression from massively dilated pulmonary arteries. The clinical diagnosis was confirmed by cardiac catheterization and angiocardiography. The infants died at age 3, 5, 30 and 90 days, respectively. Autopsy revealed, in addition to the usual components of the syndrome, absence of the ductus arteriosus or its remnants. The possible relation of \"agenesis\" of the ductus arteriosus to the pathogenesis of the severe form of this syndrome is discussed and pertinent studies are reviewed.", "contents": "\"Agenesis\" of ductus arteriosus associated with the syndrome of tetralogy of Fallot and absent pulmonary valve. Four infants with the severe form of the syndrome of tetralogy of Fallot and absent pulmonary valve are described. All had severe respiratory distress due to bronchial compression from massively dilated pulmonary arteries. The clinical diagnosis was confirmed by cardiac catheterization and angiocardiography. The infants died at age 3, 5, 30 and 90 days, respectively. Autopsy revealed, in addition to the usual components of the syndrome, absence of the ductus arteriosus or its remnants. The possible relation of \"agenesis\" of the ductus arteriosus to the pathogenesis of the severe form of this syndrome is discussed and pertinent studies are reviewed."} {"id": "PMID:1258772", "title": "Truncus arteriosus communis: truncal valve anomalies associated with small conal or truncal septal defects.", "content": "Selected specimens of truncus arteriosus communis illustrate a spectrum of anomalous truncoconal septation in which the conal and truncal septal defects are so closely approximated to the truncal valve that portions of the valve tissue extend along the free margins of the adjacent ventricular or truncal septum.", "contents": "Truncus arteriosus communis: truncal valve anomalies associated with small conal or truncal septal defects. Selected specimens of truncus arteriosus communis illustrate a spectrum of anomalous truncoconal septation in which the conal and truncal septal defects are so closely approximated to the truncal valve that portions of the valve tissue extend along the free margins of the adjacent ventricular or truncal septum."} {"id": "PMID:1258773", "title": "Duration of hospitalization in \"uncomplicated completed acute myocardial infarction\". An Ad Hoc Committee review.", "content": "The clinical and laboratory findings diagnostic of acute myocardial infarction include at least two of the following: (1) a history of pain consistent with myocardial ischemia, (2) electorcardiographic findings consistent with infarction, and (3) a rise in the serum level of specific cardiac enzymes. By the 4th or 5th day of illness, specific criteria can be applied to assign certain patients to a subset with \"uncomplicated completed acute myocardial infarction.\" These criteria include the absence of evidence of (1) continuing cardiac ischemia, (2) left ventricular failure, (3) shock, (4) important cardiac arrhythmias, (5) conduction disturbances, and (6) other serious illnesses in patients with an established acute myocardial infarction. In terms of prognosis and management, patients in this subset should be regarded as substantively different from patients in other subsets. They should respond favorably to short periods of immobilization and hospitalization than those generally used. They may remain at bed rest (modified in regard to sitting and the use of a commode) for 4 days. Subsequently, mobilization with a program of progressive activity over the ensuing 5 to 10 days should reduce the duration of hospitalization to less than the current average of 17.5 to 20.8 days for patients with acute myocardial infarction. Nine to 14 days should suffice in most instances. Current and future trials may indicate that still earlier mobilization and shorter hospitalization periods can be applied to certain patient groups, but the evidence on this point is incomplete. For the individual patient, many factors will determine the optimal duration of bed rest and hospital stay. The patient's physician must consider the therapeutic benefits that may attend earlier mobilization and shorter hospitalization while weighing potential disadvantages. When the responsible physician does not regularly care for the patient, consultation with an experienced cardiologist is desirable. Patients whose condition is classified as \"uncomplicated\" may manifest deterioration during their illness and require assignment to a subset with a different prognosis and requiring different forms of treatment. For patients with uncomplicated acute myocardial infarction, as well as those in other subsets, absolute rules for therapy are unwise and application of broader principles by the alert physician is more likely to be beneficial.", "contents": "Duration of hospitalization in \"uncomplicated completed acute myocardial infarction\". An Ad Hoc Committee review. The clinical and laboratory findings diagnostic of acute myocardial infarction include at least two of the following: (1) a history of pain consistent with myocardial ischemia, (2) electorcardiographic findings consistent with infarction, and (3) a rise in the serum level of specific cardiac enzymes. By the 4th or 5th day of illness, specific criteria can be applied to assign certain patients to a subset with \"uncomplicated completed acute myocardial infarction.\" These criteria include the absence of evidence of (1) continuing cardiac ischemia, (2) left ventricular failure, (3) shock, (4) important cardiac arrhythmias, (5) conduction disturbances, and (6) other serious illnesses in patients with an established acute myocardial infarction. In terms of prognosis and management, patients in this subset should be regarded as substantively different from patients in other subsets. They should respond favorably to short periods of immobilization and hospitalization than those generally used. They may remain at bed rest (modified in regard to sitting and the use of a commode) for 4 days. Subsequently, mobilization with a program of progressive activity over the ensuing 5 to 10 days should reduce the duration of hospitalization to less than the current average of 17.5 to 20.8 days for patients with acute myocardial infarction. Nine to 14 days should suffice in most instances. Current and future trials may indicate that still earlier mobilization and shorter hospitalization periods can be applied to certain patient groups, but the evidence on this point is incomplete. For the individual patient, many factors will determine the optimal duration of bed rest and hospital stay. The patient's physician must consider the therapeutic benefits that may attend earlier mobilization and shorter hospitalization while weighing potential disadvantages. When the responsible physician does not regularly care for the patient, consultation with an experienced cardiologist is desirable. Patients whose condition is classified as \"uncomplicated\" may manifest deterioration during their illness and require assignment to a subset with a different prognosis and requiring different forms of treatment. For patients with uncomplicated acute myocardial infarction, as well as those in other subsets, absolute rules for therapy are unwise and application of broader principles by the alert physician is more likely to be beneficial."} {"id": "PMID:1258774", "title": "\"Presystolic\" augmentation of diastolic heart sounds in atrial fibrillation.", "content": "In the presence of atrial fibrillation, the diastolic murmur of mitral stenosis can appear augmented during early systole before the mitral valve closure sound. This phenomenon has previously been thought to be due to increased blood flow velocity across the narrowing mitral valve orifice. We have observed patients in whom the third heart sound (S3) gallop, the diastolic flow murmur of atrial septal defect and mitral insufficiency and the initial muscular component of the first heart sound become more intense during this period with short, critically timed cycle lengths. This phenomenon appears to be neither peculiar to nor indicative of mitral stenosis and is probably a direct result of the initial muscular contraction of an underfilled ventricle. Either the contraction itself or the sudden deceleration of the rapidly moving flow of blood across the atrioventricular orifice may produce the sound.", "contents": "\"Presystolic\" augmentation of diastolic heart sounds in atrial fibrillation. In the presence of atrial fibrillation, the diastolic murmur of mitral stenosis can appear augmented during early systole before the mitral valve closure sound. This phenomenon has previously been thought to be due to increased blood flow velocity across the narrowing mitral valve orifice. We have observed patients in whom the third heart sound (S3) gallop, the diastolic flow murmur of atrial septal defect and mitral insufficiency and the initial muscular component of the first heart sound become more intense during this period with short, critically timed cycle lengths. This phenomenon appears to be neither peculiar to nor indicative of mitral stenosis and is probably a direct result of the initial muscular contraction of an underfilled ventricle. Either the contraction itself or the sudden deceleration of the rapidly moving flow of blood across the atrioventricular orifice may produce the sound."} {"id": "PMID:1258775", "title": "Eosinophilia and endomyocardial fibrosis.", "content": "A 12 year old boy died after a 3 year course of recurrent and progressive heart failure. His cardiac symptoms began with a marked leukocytosis (white blood cell count 188,500/mm3) due to eosinophilia (90 percent). In 6 months, the leukocytosis and eosinophilia subsided, but the patient's heart failure progressed over the next 2 1/2 years. At autopsy there was no evidence of leukemia, but a severe endocardial fibrosis extending into the myocardium was found. The origin of endomyocardial fibrosis, although unknown, appears to have been related to the eosinophilia in this patient.", "contents": "Eosinophilia and endomyocardial fibrosis. A 12 year old boy died after a 3 year course of recurrent and progressive heart failure. His cardiac symptoms began with a marked leukocytosis (white blood cell count 188,500/mm3) due to eosinophilia (90 percent). In 6 months, the leukocytosis and eosinophilia subsided, but the patient's heart failure progressed over the next 2 1/2 years. At autopsy there was no evidence of leukemia, but a severe endocardial fibrosis extending into the myocardium was found. The origin of endomyocardial fibrosis, although unknown, appears to have been related to the eosinophilia in this patient."} {"id": "PMID:1258776", "title": "Tricuspid insufficiency due to nonpenetrating trauma.", "content": "This case of tricuspid insufficiency due to nonpenetrating trauma involved a male patient who had received major chest trauma in an automobile accident, had a nonholosystolic murmur that increased slightly during inspiration on standing, and tranient electrocardiographic findings of right bundle branch block. Unlike findings in previous cases, the right atrial V wave was not dominant and was less than 8 mm Hg. An echocardiogram indicating right ventricular volume overload was an essential diagnostic tool that led to cardiac catheterization and definitive diagnosis.", "contents": "Tricuspid insufficiency due to nonpenetrating trauma. This case of tricuspid insufficiency due to nonpenetrating trauma involved a male patient who had received major chest trauma in an automobile accident, had a nonholosystolic murmur that increased slightly during inspiration on standing, and tranient electrocardiographic findings of right bundle branch block. Unlike findings in previous cases, the right atrial V wave was not dominant and was less than 8 mm Hg. An echocardiogram indicating right ventricular volume overload was an essential diagnostic tool that led to cardiac catheterization and definitive diagnosis."} {"id": "PMID:1258777", "title": "Right ventricular infarction with tricuspid insufficiency and chronic right heart failure.", "content": "A patient with chronic right heart failure and probable tricuspid insufficiency associated with an inferior myocardial infartion is described. Angiograms demonstrated total occlusion of the right coronary artery at its origin, a patent venous bypass graft to the mid-right coronary artery and hypokinesia of the inferior wall of both the right and left vebtricles. Clinical data indicated a greater impairment of right than of left ventricular function. It is proposed that infarction of the right ventricle resulted in chronic right heart failure and tricuspid insufficiency.", "contents": "Right ventricular infarction with tricuspid insufficiency and chronic right heart failure. A patient with chronic right heart failure and probable tricuspid insufficiency associated with an inferior myocardial infartion is described. Angiograms demonstrated total occlusion of the right coronary artery at its origin, a patent venous bypass graft to the mid-right coronary artery and hypokinesia of the inferior wall of both the right and left vebtricles. Clinical data indicated a greater impairment of right than of left ventricular function. It is proposed that infarction of the right ventricle resulted in chronic right heart failure and tricuspid insufficiency."} {"id": "PMID:1258783", "title": "Characterization of the ischemic process by regional metabolism.", "content": "The myocardial cell requires energy for contractile activity and for the work of internal maintenance. With the onset of ischemia mechanical performance is compromised. If the ischemia is severe and persistent, the energy necessary to maintain the internal millieu proves inadequate and cell death ensues. Ischemic heart disease is a regional phenomenon with normal and abnormal cell metabolism occurring side by side. The ischemic cell demonstrates hemodynamic, electrical and biochemical instability; its passage from a state of reversible to irreversible injury may persist for as long as 7 days and offers an opportunity to introduce interventions that may protect it and reduce ultimate infarct size. There is as yet no adequate objective means for predicting the mass of infarcted tissue. However, studies of regional metabolism, if properly conducted, may help define the adequacy of coronary vascular reserve and characterize the ischemic process. Current techniques utilize a myocardial pacing stress to induce an ischemic response. Although virtually every metabolic pathway is disrupted by severe ischemia, the assay of selected metabolities in arterial and coronary venous blood samples has provided information of diagnostic significance.", "contents": "Characterization of the ischemic process by regional metabolism. The myocardial cell requires energy for contractile activity and for the work of internal maintenance. With the onset of ischemia mechanical performance is compromised. If the ischemia is severe and persistent, the energy necessary to maintain the internal millieu proves inadequate and cell death ensues. Ischemic heart disease is a regional phenomenon with normal and abnormal cell metabolism occurring side by side. The ischemic cell demonstrates hemodynamic, electrical and biochemical instability; its passage from a state of reversible to irreversible injury may persist for as long as 7 days and offers an opportunity to introduce interventions that may protect it and reduce ultimate infarct size. There is as yet no adequate objective means for predicting the mass of infarcted tissue. However, studies of regional metabolism, if properly conducted, may help define the adequacy of coronary vascular reserve and characterize the ischemic process. Current techniques utilize a myocardial pacing stress to induce an ischemic response. Although virtually every metabolic pathway is disrupted by severe ischemia, the assay of selected metabolities in arterial and coronary venous blood samples has provided information of diagnostic significance."} {"id": "PMID:1258784", "title": "Estimation of infarct size from serum MB creatine phosphokinase activity: Applications and limitations.", "content": "Results of enzymatic estimates of infarct size have been verified under defined experimental conditions, and close correlations have been obtained between enzymatically and morphologically estimated infarct size in patients. Nevertheless, to provide a basis for improved enzymatic estimates we explored several aspects of the original model. The first order disappearance rate of creatine phosphokinase (CPK) was verified by observed high correlation coefficients of the logarithm of CPK versus time after myocardial infarction in patients or intravenous injection of purified myocardial CPK in dogs. Selected hemodynamic interventions simulating derangements accompanying myocardial infarction including acceleration of heart rate, diminution of cardiac output and reduction of renal or hepatic perfusion in conscious dogs did not markedly alter CPK disappearance. To exclude contributions from noncardiac CPK to enzymatic estimates we performed studies with the MB CPK isoenzyme. Under standard assay conditions, MB CPK was found virtually exclusively in myocardium. Serial serum MB CPK curves paralleled those of total CPK from patients with uncomplicated infarction. Similar MB curves were obtained even in patients whose noncardiac CPK values distorted the total CPK curve after intramuscular injections. The correlation coefficient between infarct size estimated from total CPK and MB CPK was 0.97 in 12 patients with hemodynamically uncomplicated infarction. Thus, hemodynamic perturbations associated with infarction are unlikely to affect CPK disappearance and hence should not lead to spurious enzymatic estimates of infarct size. Furthermore, improved enzymatic estimates can be obtained by quantitative assay of MB CPK, a more specific myocardial marker, avoiding spurious estimates due to contributions from noncardiac enzyme.", "contents": "Estimation of infarct size from serum MB creatine phosphokinase activity: Applications and limitations. Results of enzymatic estimates of infarct size have been verified under defined experimental conditions, and close correlations have been obtained between enzymatically and morphologically estimated infarct size in patients. Nevertheless, to provide a basis for improved enzymatic estimates we explored several aspects of the original model. The first order disappearance rate of creatine phosphokinase (CPK) was verified by observed high correlation coefficients of the logarithm of CPK versus time after myocardial infarction in patients or intravenous injection of purified myocardial CPK in dogs. Selected hemodynamic interventions simulating derangements accompanying myocardial infarction including acceleration of heart rate, diminution of cardiac output and reduction of renal or hepatic perfusion in conscious dogs did not markedly alter CPK disappearance. To exclude contributions from noncardiac CPK to enzymatic estimates we performed studies with the MB CPK isoenzyme. Under standard assay conditions, MB CPK was found virtually exclusively in myocardium. Serial serum MB CPK curves paralleled those of total CPK from patients with uncomplicated infarction. Similar MB curves were obtained even in patients whose noncardiac CPK values distorted the total CPK curve after intramuscular injections. The correlation coefficient between infarct size estimated from total CPK and MB CPK was 0.97 in 12 patients with hemodynamically uncomplicated infarction. Thus, hemodynamic perturbations associated with infarction are unlikely to affect CPK disappearance and hence should not lead to spurious enzymatic estimates of infarct size. Furthermore, improved enzymatic estimates can be obtained by quantitative assay of MB CPK, a more specific myocardial marker, avoiding spurious estimates due to contributions from noncardiac enzyme."} {"id": "PMID:1258785", "title": "Temporal relation of epicardial electrographic, contractile and biochemical changes after acute coronary occlusion and reperfusion.", "content": "The increasing use of changes in the S-T segment of local epicardial electrograms to quantitate myocardial infarct size has led to the need for a better understanding of this method. Accordingly, we studied the local electrographic, tension and biochemical changes that occurred after coronary occlusion and subsequent reperfusion in 44 dogs using epicardial electrograms from 10 to 12 sites, Walton-Brodie strain gauge arches and myocardial ratios of potassium ion to sodium ion (K+/Na+). After coronary occlusion for 1 hour, total S-T segment elevation increased from 10.2 +/- 2.4 to 78.3 +/- 13.7 mv (P less than 0.001) and tension development decreased to 63.6 +/- 7.0% of control value (P less than 0.001); occlusion for 3 hours resulted in a total S-T segment elevation increase from 5.8 +/- 3.4 to 56.7 +/- 8.7 mv (P less than 0.001) and a tension decrease to 61.4 +/- 5.3% (P less than 0.001) of control value. After reperfusion two types of response were observed. In nine experiments new local pathologic Q waves appeared in an average of 5.3 of 8.2 ischemic electrode sites within 5 to 10 minutes of reperfusion concomitant with a marked further decrease in total tension from 67.3 +/- 5.5% to 42.4 +/- 6.0% of control value (P less than 0.001). Simultaneously, total S-T elevation decreased from 66.1 +/- 8.2 to 25.3 +/- 3.4 mv (P less than 0.001). In seven experiments no Q waves appeared after reperfusion and there was no significant change in tension. Total S-T elevation again decreased from 58.3 +/- 12.7 to 27.1 +/- 5.7 mv (P less than 0.025). When normal saline solution was perfused distal to the coronary arterial occlusion total S-T elevation decreased from 68.0 +/- 3.6 to 36.3 +/- 5.2 mv (P less than 0.001). After 3 hours of coronary occlusion, myocardial K+ decreased and Na+ increased in the ischemic zone, resulting in a significant decrease in the K+/Na+ ratio (P less than 0.005). Reperfusion for 2 hours resulted in a further depletion of K+ and an increase in Na+ with a resultant complete reversal of the K+/Na+ ratio (P less than 0.001). In summary, after reperfusion the S-T segment abnormalities rapidly decreased in all experiments despite the appearance of new Q waves in more than half of these studies concomitant with either a decrease or no change in contractile ability and continuing myocardial K+ loss and Na+ accumulation. S-T segment mapping therefore appears to be of limited value in assessing the effect of reperfusion on infarct size. The decrease in S-T segments that occurred with perfusion of either blood or saline solution suggests a \"washout\" phenomenon.", "contents": "Temporal relation of epicardial electrographic, contractile and biochemical changes after acute coronary occlusion and reperfusion. The increasing use of changes in the S-T segment of local epicardial electrograms to quantitate myocardial infarct size has led to the need for a better understanding of this method. Accordingly, we studied the local electrographic, tension and biochemical changes that occurred after coronary occlusion and subsequent reperfusion in 44 dogs using epicardial electrograms from 10 to 12 sites, Walton-Brodie strain gauge arches and myocardial ratios of potassium ion to sodium ion (K+/Na+). After coronary occlusion for 1 hour, total S-T segment elevation increased from 10.2 +/- 2.4 to 78.3 +/- 13.7 mv (P less than 0.001) and tension development decreased to 63.6 +/- 7.0% of control value (P less than 0.001); occlusion for 3 hours resulted in a total S-T segment elevation increase from 5.8 +/- 3.4 to 56.7 +/- 8.7 mv (P less than 0.001) and a tension decrease to 61.4 +/- 5.3% (P less than 0.001) of control value. After reperfusion two types of response were observed. In nine experiments new local pathologic Q waves appeared in an average of 5.3 of 8.2 ischemic electrode sites within 5 to 10 minutes of reperfusion concomitant with a marked further decrease in total tension from 67.3 +/- 5.5% to 42.4 +/- 6.0% of control value (P less than 0.001). Simultaneously, total S-T elevation decreased from 66.1 +/- 8.2 to 25.3 +/- 3.4 mv (P less than 0.001). In seven experiments no Q waves appeared after reperfusion and there was no significant change in tension. Total S-T elevation again decreased from 58.3 +/- 12.7 to 27.1 +/- 5.7 mv (P less than 0.025). When normal saline solution was perfused distal to the coronary arterial occlusion total S-T elevation decreased from 68.0 +/- 3.6 to 36.3 +/- 5.2 mv (P less than 0.001). After 3 hours of coronary occlusion, myocardial K+ decreased and Na+ increased in the ischemic zone, resulting in a significant decrease in the K+/Na+ ratio (P less than 0.005). Reperfusion for 2 hours resulted in a further depletion of K+ and an increase in Na+ with a resultant complete reversal of the K+/Na+ ratio (P less than 0.001). In summary, after reperfusion the S-T segment abnormalities rapidly decreased in all experiments despite the appearance of new Q waves in more than half of these studies concomitant with either a decrease or no change in contractile ability and continuing myocardial K+ loss and Na+ accumulation. S-T segment mapping therefore appears to be of limited value in assessing the effect of reperfusion on infarct size. The decrease in S-T segments that occurred with perfusion of either blood or saline solution suggests a \"washout\" phenomenon."} {"id": "PMID:1258786", "title": "Significance of S-T segment elevations in acute myocardial ischemia. Evaluation with intracoronary electrode technique.", "content": "A method is described for measuring intracoronary S-T segment elevations in the closed chest, a technique that appears to provide more reliable measurements of myocardial ischemia. Electrodes were inserted through intracoronary balloon catheters that were placed within a coronary artery and its adjoining vein both proximal and at several points distal to a coronary occlusion. Intracoronary arterial and adjacent venous electrocardiograms produced equivalent tracings. The intracoronary S-T segment elevations after coronary occlusion resembled those recorded from the epicardial surface but were free of artifacts noted in open chest studies. Study of progressive alterations of the intracoronary S-T segment after proximal occlusion of the left anterior descending coronary artery in 18 closed chest dogs revealed a peak segment elevation of 3.2 +/- 0.6 mv within 5 minutes, followed within 2 to 3 hours by spontaneous reduction by more than 40% of the S-T elevation over the occluded zone. In 44% of these animals, the S-T elevation decreased spontaneously to less than 1 mv, and in 22% it decreased to the preocclusion control level within 2 hours of occlusion. This spontaneous decrease in S-T elevation was frequently followed by a secondary increase and then S-T segment fluctuations. Reperfusion of the left anterior descending coronary artery after 30 to 60 minutes of occlusion generally led to a prompt reduction in S-T elevation. In some cases S-T elevations persisted up to 14 hours of occlusion, were reduced after reperfusion and exhibited a renewed pronounced increase after subsequent reocclusion of the left anterior descending coronary artery. During the 1st hour after occlusion, the early S-T segment elevation followed by spontaneous reduction reduction generally corresponded temporally with the derangements in myocardial lactate extraction and potassium loss. However, after 1 hour of occlusion no clear-cut correlation could be established between S-T fluctuations and changes in hemodynamic or myocardial metabolic measurements. We conclude that the new closed chest intracoronary electrocardiographic S-T technique might be of use for monitoring the early ischemic myocardial derangements and to assess benefits or drawbacks of treatment in both the experimental animal and man. Correspondence of S-T segment elevation with lactate and potassium alterations in the coronary-occluded region in the 1st hour after occlusion indicates that S-T segment elevation might represent an index of early myocardial ischemia. The spontaneous S-T changes that follow coronary occlusion must be taken into consideration when investigators utilize S-T segment modification as a sign of effectiveness of treatment.", "contents": "Significance of S-T segment elevations in acute myocardial ischemia. Evaluation with intracoronary electrode technique. A method is described for measuring intracoronary S-T segment elevations in the closed chest, a technique that appears to provide more reliable measurements of myocardial ischemia. Electrodes were inserted through intracoronary balloon catheters that were placed within a coronary artery and its adjoining vein both proximal and at several points distal to a coronary occlusion. Intracoronary arterial and adjacent venous electrocardiograms produced equivalent tracings. The intracoronary S-T segment elevations after coronary occlusion resembled those recorded from the epicardial surface but were free of artifacts noted in open chest studies. Study of progressive alterations of the intracoronary S-T segment after proximal occlusion of the left anterior descending coronary artery in 18 closed chest dogs revealed a peak segment elevation of 3.2 +/- 0.6 mv within 5 minutes, followed within 2 to 3 hours by spontaneous reduction by more than 40% of the S-T elevation over the occluded zone. In 44% of these animals, the S-T elevation decreased spontaneously to less than 1 mv, and in 22% it decreased to the preocclusion control level within 2 hours of occlusion. This spontaneous decrease in S-T elevation was frequently followed by a secondary increase and then S-T segment fluctuations. Reperfusion of the left anterior descending coronary artery after 30 to 60 minutes of occlusion generally led to a prompt reduction in S-T elevation. In some cases S-T elevations persisted up to 14 hours of occlusion, were reduced after reperfusion and exhibited a renewed pronounced increase after subsequent reocclusion of the left anterior descending coronary artery. During the 1st hour after occlusion, the early S-T segment elevation followed by spontaneous reduction reduction generally corresponded temporally with the derangements in myocardial lactate extraction and potassium loss. However, after 1 hour of occlusion no clear-cut correlation could be established between S-T fluctuations and changes in hemodynamic or myocardial metabolic measurements. We conclude that the new closed chest intracoronary electrocardiographic S-T technique might be of use for monitoring the early ischemic myocardial derangements and to assess benefits or drawbacks of treatment in both the experimental animal and man. Correspondence of S-T segment elevation with lactate and potassium alterations in the coronary-occluded region in the 1st hour after occlusion indicates that S-T segment elevation might represent an index of early myocardial ischemia. The spontaneous S-T changes that follow coronary occlusion must be taken into consideration when investigators utilize S-T segment modification as a sign of effectiveness of treatment."} {"id": "PMID:1258787", "title": "Inotropic agents and infarct size. Theoretical and practical considerations.", "content": "Recent data demonstrating the ability of interventions that alter the balance between myocardial oxygen demand and supply to affect infarct size are reviewed. The effects of inotropic agents on the determinants of myocardial oxygen consumption and coronary blood flow are discussed relative to the potential of these drugs to decrease or increase infarct size in the experimental animal and in man. The applicability of the animal data to the clinical situation is discussed and, on the basis of these considerations, guidelines are presented for the use of inotropic agents in patients with acute myocardial infarction.", "contents": "Inotropic agents and infarct size. Theoretical and practical considerations. Recent data demonstrating the ability of interventions that alter the balance between myocardial oxygen demand and supply to affect infarct size are reviewed. The effects of inotropic agents on the determinants of myocardial oxygen consumption and coronary blood flow are discussed relative to the potential of these drugs to decrease or increase infarct size in the experimental animal and in man. The applicability of the animal data to the clinical situation is discussed and, on the basis of these considerations, guidelines are presented for the use of inotropic agents in patients with acute myocardial infarction."} {"id": "PMID:1258788", "title": "Effect of hypertonic mannitol and intraaortic counterpulsation on regional myocardial blood flow and ventricular performance in dogs during myocardial ischemia.", "content": "Studies were performed to determine if intervention with hypertonic mannitol and intraaortic balloon counterpulsation increases regional myocardial blood flow during acute myocardial ischemia. Anesthetized dogs on right heart bypass were studied. Heart rate was kept constant by atrial pacing. Myocardial ischemia was provided by ligating the proximal left anterior descending coronary artery for 12 minute periods. Infusion of hypertonic mannitol begun immediately after ligation increased coronary blood flow to the ischemic area by 36 +/- 9.0% (standard error) (P less than 0.01) and to the nonischemic left ventricle by 21 +/- 8.8% (P less than 0.05) as compared with flow in the same regions during the control coronary ligation. Intraaortic balloon counterpulsation begun immediately after ligation increased regional coronary flow to the ischemic region by 20 +/- 8.4% (P less than 0.05) but did not significantly alter flow to the nonischemic left ventricle as compared with levels during the control ligation. Combined intraaortic counterpulsation and hypertonic mannitol increased coronary flow to the ischemic region by 46 +/- 13% (P less than 0.02) and to the nonischemic left ventricle by 59 +/- 22% (P less than 0.05) as compared with flow during occlusion of the left anterior descending artery with mannitol alone. The data demonstrate that both hypertonic mannitol and intraaortic counterpulsation increase left ventricular ischemic regional flow and that combined hypertonic mannitol and intraaortic balloon counterpulsation provide a greater increase in regional coronary blood flow to both the ischemic and nonischemic regions of the left ventricle than mannitol alone.", "contents": "Effect of hypertonic mannitol and intraaortic counterpulsation on regional myocardial blood flow and ventricular performance in dogs during myocardial ischemia. Studies were performed to determine if intervention with hypertonic mannitol and intraaortic balloon counterpulsation increases regional myocardial blood flow during acute myocardial ischemia. Anesthetized dogs on right heart bypass were studied. Heart rate was kept constant by atrial pacing. Myocardial ischemia was provided by ligating the proximal left anterior descending coronary artery for 12 minute periods. Infusion of hypertonic mannitol begun immediately after ligation increased coronary blood flow to the ischemic area by 36 +/- 9.0% (standard error) (P less than 0.01) and to the nonischemic left ventricle by 21 +/- 8.8% (P less than 0.05) as compared with flow in the same regions during the control coronary ligation. Intraaortic balloon counterpulsation begun immediately after ligation increased regional coronary flow to the ischemic region by 20 +/- 8.4% (P less than 0.05) but did not significantly alter flow to the nonischemic left ventricle as compared with levels during the control ligation. Combined intraaortic counterpulsation and hypertonic mannitol increased coronary flow to the ischemic region by 46 +/- 13% (P less than 0.02) and to the nonischemic left ventricle by 59 +/- 22% (P less than 0.05) as compared with flow during occlusion of the left anterior descending artery with mannitol alone. The data demonstrate that both hypertonic mannitol and intraaortic counterpulsation increase left ventricular ischemic regional flow and that combined hypertonic mannitol and intraaortic balloon counterpulsation provide a greater increase in regional coronary blood flow to both the ischemic and nonischemic regions of the left ventricle than mannitol alone."} {"id": "PMID:1258789", "title": "On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs.", "content": "Propranolol has been shown to reduce the extent of necrosis that develops after temporary coronary occlusion in dogs. To determine whether this protective action was related to beta adrenergic blockade or to direct effects, necrosis was quantitated in the posterior papillary muscle 2 to 4 days after 40 minute periods of coronary occlusion in anesthetized open chest dogs. Groups of dogs either were untreated or were pretreated with doses of d,l-propranolol, 0.005 to 5 mg/kg body weight, or doses of d-propranolol 2.5 or 5 mg/kg. Necrosis was greatly reduced in dogs treated with 5 mg/kg of d, l-propranolol. This protective effect was significant but quantitatively less with 0.5 and 0.05 mg/kg of d, l-propranolol. A dose of 0.005 mg/kg d, l-propranolol and d-propranolol failed to alter myocardial necrosis significantly. The dose-related reduction of necrosis with d, l-propranolol correlated with a similar dose relation for beta adrenergic blockade and suggested that a protective effect was related to beta blockade. The reduction of necrosis with 0.05 and 0.5 mg/kg of d, l-propranolol (a level at which direct \"membrane stabilizing\" effects are insignificant) suggested that direct effects were not essential for protection. The negative results with d-propranolol further support our conclusion that propranolol reduces myocardial ischemic injury through beta adrenergic blockade rather than through direct myocardial actions.", "contents": "On the nature of protection by propranolol against myocardial necrosis after temporary coronary occlusion in dogs. Propranolol has been shown to reduce the extent of necrosis that develops after temporary coronary occlusion in dogs. To determine whether this protective action was related to beta adrenergic blockade or to direct effects, necrosis was quantitated in the posterior papillary muscle 2 to 4 days after 40 minute periods of coronary occlusion in anesthetized open chest dogs. Groups of dogs either were untreated or were pretreated with doses of d,l-propranolol, 0.005 to 5 mg/kg body weight, or doses of d-propranolol 2.5 or 5 mg/kg. Necrosis was greatly reduced in dogs treated with 5 mg/kg of d, l-propranolol. This protective effect was significant but quantitatively less with 0.5 and 0.05 mg/kg of d, l-propranolol. A dose of 0.005 mg/kg d, l-propranolol and d-propranolol failed to alter myocardial necrosis significantly. The dose-related reduction of necrosis with d, l-propranolol correlated with a similar dose relation for beta adrenergic blockade and suggested that a protective effect was related to beta blockade. The reduction of necrosis with 0.05 and 0.5 mg/kg of d, l-propranolol (a level at which direct \"membrane stabilizing\" effects are insignificant) suggested that direct effects were not essential for protection. The negative results with d-propranolol further support our conclusion that propranolol reduces myocardial ischemic injury through beta adrenergic blockade rather than through direct myocardial actions."} {"id": "PMID:1258790", "title": "Metabolic evaluation of agents designed to protect the ischemic myocardium and to reduce infarct size.", "content": "There is as yet no adequate animal mode for human myocardial ischemia. The commonly utilized technique of coronary arterial ligation in large animals may induce regional ischemia but introduces variables that make it difficult to compare studies in different laboratories. A model of global ischemia in an isolated perfused rat heart that offers a rapid, inexpensive means for producing graded, controlled, stable state and reproducible ischemia is described. The technique has been utilized with success to study the hemodynamic and metabolic effects of ischemia and to evaluate pharmacologic interventions designed to protect the ischemic myocardium. Propranolol has been shown to improve bioenergetics and reduce anaerobic glycolysis by a depression of the hemodynamic response of ischemic myocardium. Methylprednisolone appears to exert its primary effect by direct coronary vasodilation, increasing resting or control flow and providing an enhanced reserve when ischemia is imposed. Mannitol improves cardiac performance by reducing the increased myocardial cell water content induced by hypoxia or anoxia.", "contents": "Metabolic evaluation of agents designed to protect the ischemic myocardium and to reduce infarct size. There is as yet no adequate animal mode for human myocardial ischemia. The commonly utilized technique of coronary arterial ligation in large animals may induce regional ischemia but introduces variables that make it difficult to compare studies in different laboratories. A model of global ischemia in an isolated perfused rat heart that offers a rapid, inexpensive means for producing graded, controlled, stable state and reproducible ischemia is described. The technique has been utilized with success to study the hemodynamic and metabolic effects of ischemia and to evaluate pharmacologic interventions designed to protect the ischemic myocardium. Propranolol has been shown to improve bioenergetics and reduce anaerobic glycolysis by a depression of the hemodynamic response of ischemic myocardium. Methylprednisolone appears to exert its primary effect by direct coronary vasodilation, increasing resting or control flow and providing an enhanced reserve when ischemia is imposed. Mannitol improves cardiac performance by reducing the increased myocardial cell water content induced by hypoxia or anoxia."} {"id": "PMID:1258791", "title": "Effect of nitroprusside on local contractile performance after coronary ligation and reperfusion.", "content": "To study the effects of nitroprusside infusion on the regional contractile performance of the left ventricle after coronary occlusion, local tension and segment length of the ischemic, border and nonischemic zones were studied using Walton-Brodie strain gauge arches and mercury-in-Silastic tubing segment length gauges in open chest dogs. The effect of this intervention on the time period for functional reversibility of the affected areas after revascularization was also examined. Fifteen minutes after occlusion of the left anterior descending coronary artery, nitroprusside (4 to 11 mug/kg per min) was infused to keep systolic pressure 20 to 25% below control levels for 2 hours after occlusion and then 1 hour after reperfusion. The ischemic zone showed no change in either tension or length although there was a gradual continuing decrease in tension. However, in the border zone total tension which had decreased to 81.4 +/- 9.6 (standard error of the mean) percent of control level 15 minutes after coronary occlusion, increased to 87.5 +/- 11.3% immediately after nitroprusside infusion and continued at that level for 2 hours. Preejection tension rate of tension rise and ejection tension demonstrated parallel increases. Segment length, which had increased to 144.1 +/- 4.5% of control level after coronary occlusion, declined to 115 +/- 10.7% (P less than 0.02) immediately after the onset of infusion. The nonischemic zone showed a sustained increase in all tension variables (P less than 0.01) and a decrease in segment length during the period of nitroprusside infusion with a return to control value after discontinuation of the infusion. The immediate deterioration in tension in the ischemic zone caused by reperfusion after 2 hours of occlusion was prevented by nitroprusside. The border zone continued to maintain improved tension after reperfusion but exhibited an immediate decrease from 84.1 +/- 7.8% to 69.1 +/- 11.7% (P less than 0.05) after discontinuation of nitroprusside. In summary, nitroprusside infusion provides a sustained increase in tension and decrease in length of the border and the nonischemic zones after acute coronary occlusion whereas the ischemic zone remains unaffected. Although administration of nitroprusside fails to prolong the time period for functional reversibility of the affected zones with reperfusion, it appears to prevent further deterioration.", "contents": "Effect of nitroprusside on local contractile performance after coronary ligation and reperfusion. To study the effects of nitroprusside infusion on the regional contractile performance of the left ventricle after coronary occlusion, local tension and segment length of the ischemic, border and nonischemic zones were studied using Walton-Brodie strain gauge arches and mercury-in-Silastic tubing segment length gauges in open chest dogs. The effect of this intervention on the time period for functional reversibility of the affected areas after revascularization was also examined. Fifteen minutes after occlusion of the left anterior descending coronary artery, nitroprusside (4 to 11 mug/kg per min) was infused to keep systolic pressure 20 to 25% below control levels for 2 hours after occlusion and then 1 hour after reperfusion. The ischemic zone showed no change in either tension or length although there was a gradual continuing decrease in tension. However, in the border zone total tension which had decreased to 81.4 +/- 9.6 (standard error of the mean) percent of control level 15 minutes after coronary occlusion, increased to 87.5 +/- 11.3% immediately after nitroprusside infusion and continued at that level for 2 hours. Preejection tension rate of tension rise and ejection tension demonstrated parallel increases. Segment length, which had increased to 144.1 +/- 4.5% of control level after coronary occlusion, declined to 115 +/- 10.7% (P less than 0.02) immediately after the onset of infusion. The nonischemic zone showed a sustained increase in all tension variables (P less than 0.01) and a decrease in segment length during the period of nitroprusside infusion with a return to control value after discontinuation of the infusion. The immediate deterioration in tension in the ischemic zone caused by reperfusion after 2 hours of occlusion was prevented by nitroprusside. The border zone continued to maintain improved tension after reperfusion but exhibited an immediate decrease from 84.1 +/- 7.8% to 69.1 +/- 11.7% (P less than 0.05) after discontinuation of nitroprusside. In summary, nitroprusside infusion provides a sustained increase in tension and decrease in length of the border and the nonischemic zones after acute coronary occlusion whereas the ischemic zone remains unaffected. Although administration of nitroprusside fails to prolong the time period for functional reversibility of the affected zones with reperfusion, it appears to prevent further deterioration."} {"id": "PMID:1258792", "title": "Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion.", "content": "In anesthetized open chest dogs, hydrocortisone (50 mg/kg body weight administered 30 minutes after occlusion and 25 mg/kg 12 hours later) substantially reduced the size of myocardial infarcts, as reflected by both myocardial creatine phosphokinase activity and histologic appearance 24 hours later. Similarly, hyaluronidase, which increases diffusion through the extracellular space and presumably facilitates delivery of substrate to ischemic cells, also reduced the extent of myocardial necrosis after coronary occlusion in the dog. In view of the salutary effects of hyaluronidase and the absence of serious side effects, this agent was administered clinically to two groups of patients, who were compared with two groups of untreated control subjects. Hyaluronidase (500 National Formulary units/kg X 8) was shown to result in a significantly more rapid reduction in the magnitude and the extent of precordial S-T segment elevations, and in patients treated within 4 hours a tendency to a lower incidence rate of Q waves and a smaller reduction of R waves.", "contents": "Effects of hyaluronidase and hydrocortisone on myocardial necrosis after coronary occlusion. In anesthetized open chest dogs, hydrocortisone (50 mg/kg body weight administered 30 minutes after occlusion and 25 mg/kg 12 hours later) substantially reduced the size of myocardial infarcts, as reflected by both myocardial creatine phosphokinase activity and histologic appearance 24 hours later. Similarly, hyaluronidase, which increases diffusion through the extracellular space and presumably facilitates delivery of substrate to ischemic cells, also reduced the extent of myocardial necrosis after coronary occlusion in the dog. In view of the salutary effects of hyaluronidase and the absence of serious side effects, this agent was administered clinically to two groups of patients, who were compared with two groups of untreated control subjects. Hyaluronidase (500 National Formulary units/kg X 8) was shown to result in a significantly more rapid reduction in the magnitude and the extent of precordial S-T segment elevations, and in patients treated within 4 hours a tendency to a lower incidence rate of Q waves and a smaller reduction of R waves."} {"id": "PMID:1258793", "title": "Beneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia.", "content": "The metabolic and hemodynamic effects of methylprednisolone sodium succinate (40 mg/kg body weight) after acute myocardial ischemia were determined in 24 heparinized mongrel dogs. Myocardial ischemia was produced by ligation of the left anterior descending coronary artery. Catheters in the coronary sinus and the vein draining the left anterior descending coronary arterial area were used to collect blood samples from nonischemic and ischemic myocardium. Lactate, pyruvate, glucose, free fatty acids and oxygen were measured in arterial and venous blood from ischemic and nonischemic areas before and 3, 30 and 60 minutes after myocardial ischemia in animals with (Group II) and without (Group I) steroid treatment. In both Groups I and II glucose, lactate, free fatty acids, oxygen and coronary blood flow in nonischemic areas were not significantly changed, whereas glucose uptake in ischemic areas was significantly increased with myocardial ischemia and remained elevated. In Group I lactate uptake in ischemic areas became negative after coronary arterial ligation and remained so; in Group II, it increased after 30 (70%) and 60 (111%) minutes. Free fatty acid uptake in ischemic areas was reduced after myocardial ischemia in Group I, but in Group II it increased after 30 (224%) and 60 minutes (173%), and there was a concomitant increase in oxygen uptake. Pyruvate uptake in nonischemic areas decreased after 60 minutes in Group I, whereas it was reduced after 30 (68%) and 60 minutes (513%) in Group II. The changes were similar in ischemic myocardium. There were no significant changes in hemodynamic indexes. Coronary blood flow in ischemic areas decreased in Group I after myocardial ischemia and further after 30 and 60 minutes, but in Group II it increased after 30 (82%) and 60 minutes (53%). The data indicate that administration of methylprednisolone results in improved collateral blood flow into the infarcted area and a significantly improved metabolic response of ischemic myocardium. The glucocorticoid may also have a direct benefical effect on carbohydrate metabolism and cause the increased pyruvate neccesary to maintain the generation of energy-producing substrates. The results also suggest that methylprednisolone increases cell survival time and results in greater salvage of ischemic myocardium.", "contents": "Beneficial metabolic effects of methylprednisolone sodium succinate in acute myocardial ischemia. The metabolic and hemodynamic effects of methylprednisolone sodium succinate (40 mg/kg body weight) after acute myocardial ischemia were determined in 24 heparinized mongrel dogs. Myocardial ischemia was produced by ligation of the left anterior descending coronary artery. Catheters in the coronary sinus and the vein draining the left anterior descending coronary arterial area were used to collect blood samples from nonischemic and ischemic myocardium. Lactate, pyruvate, glucose, free fatty acids and oxygen were measured in arterial and venous blood from ischemic and nonischemic areas before and 3, 30 and 60 minutes after myocardial ischemia in animals with (Group II) and without (Group I) steroid treatment. In both Groups I and II glucose, lactate, free fatty acids, oxygen and coronary blood flow in nonischemic areas were not significantly changed, whereas glucose uptake in ischemic areas was significantly increased with myocardial ischemia and remained elevated. In Group I lactate uptake in ischemic areas became negative after coronary arterial ligation and remained so; in Group II, it increased after 30 (70%) and 60 (111%) minutes. Free fatty acid uptake in ischemic areas was reduced after myocardial ischemia in Group I, but in Group II it increased after 30 (224%) and 60 minutes (173%), and there was a concomitant increase in oxygen uptake. Pyruvate uptake in nonischemic areas decreased after 60 minutes in Group I, whereas it was reduced after 30 (68%) and 60 minutes (513%) in Group II. The changes were similar in ischemic myocardium. There were no significant changes in hemodynamic indexes. Coronary blood flow in ischemic areas decreased in Group I after myocardial ischemia and further after 30 and 60 minutes, but in Group II it increased after 30 (82%) and 60 minutes (53%). The data indicate that administration of methylprednisolone results in improved collateral blood flow into the infarcted area and a significantly improved metabolic response of ischemic myocardium. The glucocorticoid may also have a direct benefical effect on carbohydrate metabolism and cause the increased pyruvate neccesary to maintain the generation of energy-producing substrates. The results also suggest that methylprednisolone increases cell survival time and results in greater salvage of ischemic myocardium."} {"id": "PMID:1258794", "title": "Methylprednisolone treatment in acute myocardial infarction. Effect on regional and global myocardial function.", "content": "The effects of methylprednisolong treatment on acute myocardial ischemia were studied in nine closed chest dogs. After 1 hour of proximal occlusion of the left anterior descending coronary artery, an intravenous bolus injection (50 mg/kg body weight) of methylprednisolone was administered and its effects studied during an additional 2 hours of occlusion. After 2 hours of treatment the following significant mean alterations from levels after 1 hour of occlusion were noted: an increase of 16.7% in heart rate and decreases of 23% in left ventricular end-diastolic pressure, 32% in stroke volume, 14% in cardiac output and 37% in stroke work. Peak systolic pressure, maximal rate of rise of left ventricular pressure (dP/dt), left ventricular end-diastolic volume, systemic vascular resistance and coronary sinus blood flow changed less than 10%. Ejection fraction and regional cardiac wall motion were not improved. Metabolic dysfunction of the coronary-occluded myocardium, revealed by regional lactate as well as potassium derangements, persisted throughout the 2 hour treatment period. Comparison of these results with equivalent data from an untreated series of nine dogs with 3 hours of occlusion demonstrated no improvement in the treated series. Methylprednistone failed to restore regional cardiac metabolic and mechanical function, and treatment was associated with a further rise in S-T segment elevations. Administration of methylprednisolone after 1 hour of proximal left anterior descending coronary occlusion apparently does not reverse cardiac dysfunction in the first 2 hours of treatment.", "contents": "Methylprednisolone treatment in acute myocardial infarction. Effect on regional and global myocardial function. The effects of methylprednisolong treatment on acute myocardial ischemia were studied in nine closed chest dogs. After 1 hour of proximal occlusion of the left anterior descending coronary artery, an intravenous bolus injection (50 mg/kg body weight) of methylprednisolone was administered and its effects studied during an additional 2 hours of occlusion. After 2 hours of treatment the following significant mean alterations from levels after 1 hour of occlusion were noted: an increase of 16.7% in heart rate and decreases of 23% in left ventricular end-diastolic pressure, 32% in stroke volume, 14% in cardiac output and 37% in stroke work. Peak systolic pressure, maximal rate of rise of left ventricular pressure (dP/dt), left ventricular end-diastolic volume, systemic vascular resistance and coronary sinus blood flow changed less than 10%. Ejection fraction and regional cardiac wall motion were not improved. Metabolic dysfunction of the coronary-occluded myocardium, revealed by regional lactate as well as potassium derangements, persisted throughout the 2 hour treatment period. Comparison of these results with equivalent data from an untreated series of nine dogs with 3 hours of occlusion demonstrated no improvement in the treated series. Methylprednistone failed to restore regional cardiac metabolic and mechanical function, and treatment was associated with a further rise in S-T segment elevations. Administration of methylprednisolone after 1 hour of proximal left anterior descending coronary occlusion apparently does not reverse cardiac dysfunction in the first 2 hours of treatment."} {"id": "PMID:1258795", "title": "Influence of vasodilators upon function and metabolism of ischemic myocardium.", "content": "Although the systemic hemodynamic effects of vasodilators such as nitroprusside, phentolamine and nitrates are well known, relatively little information is available regarding their effects upon the function and metabolism of ischemic myocardium. Experimental and clinical studies indicate that vasodilators improve the mechanical performance of regional ischemic myocardium, probably by simultaneous reduction of peripheral resistance and reduction of the degree of ischemia. The majority of evidence, although still controversial, seems to indicate that myocardial perfusion can also be increased, particularly when coronary collateral vessels are present. Concomitant reduction in preload contributes to reduced oxygen demand, as evidenced by findings of reduced oxygen extraction. Thus, the balance of the oxygen supply and demand may be improved as indicated by decreases in lactate production. In addition, limited evidence in experimental animals and man suggests that vasodilators may also reduce the extent of myocardial injury as measured by S-T segment mapping and the creatine phosphokinase (CPK) release technique. However, these effects are contingent upon the arterial pressure response, and directionally opposite results may be anticipated if hypotension occurs. Since the mechanism of action of vasodilators is reasonably well understood, vasodilator therapy can be administered safely in anticipation of both improvement in total cardiac performance and a decrease in severity of ischemia.", "contents": "Influence of vasodilators upon function and metabolism of ischemic myocardium. Although the systemic hemodynamic effects of vasodilators such as nitroprusside, phentolamine and nitrates are well known, relatively little information is available regarding their effects upon the function and metabolism of ischemic myocardium. Experimental and clinical studies indicate that vasodilators improve the mechanical performance of regional ischemic myocardium, probably by simultaneous reduction of peripheral resistance and reduction of the degree of ischemia. The majority of evidence, although still controversial, seems to indicate that myocardial perfusion can also be increased, particularly when coronary collateral vessels are present. Concomitant reduction in preload contributes to reduced oxygen demand, as evidenced by findings of reduced oxygen extraction. Thus, the balance of the oxygen supply and demand may be improved as indicated by decreases in lactate production. In addition, limited evidence in experimental animals and man suggests that vasodilators may also reduce the extent of myocardial injury as measured by S-T segment mapping and the creatine phosphokinase (CPK) release technique. However, these effects are contingent upon the arterial pressure response, and directionally opposite results may be anticipated if hypotension occurs. Since the mechanism of action of vasodilators is reasonably well understood, vasodilator therapy can be administered safely in anticipation of both improvement in total cardiac performance and a decrease in severity of ischemia."} {"id": "PMID:1258796", "title": "Diastolic retroperfusion of acutely ischemic myocardium.", "content": "The effectiveness of coronary venous retroperfusion treatment of an ischemic myocardial segment was assessed by measurements of regional and global myocardial function in 16 dogs. The left anterior descending coronary artery was acutely occluded for 75 minutes. After the first 30 minutes of occlusion, diastolic retroperfusion was instituted for 45 minutes by synchronized pumping of arterial blood from the brachial artery into the anterior interventricular coronary vein. Data collected in the preocclusion control period, during occlusion and the subsequent retroperfusion period included simultaneous measurement os ischemic and border zone myocardial forces, epicardial electrocardiographic S-T segments, intracoronary pressure, coronary blood flow and oxygen pressure (PO2) sampled distal to the site of occlusion. Retroperfusion resulted in significant improvement from the level of regional dysfunction observed after 30 minutes of occlusion: Ischemic zone myocardial force increased 106%, epicardial S-T elevation decreased 46%, normalized peripheral left anterior descending coronary arterial flow increased 50% and distal left anterior descending PO2 decreased 44%. These regional improvements were significant when compared with findings in an untreated series of 12 dogs with 75 minutes occlusion of the left anterior descending coronary artery. Diastolic-augmented coronary venous retroperfusion with arterial blood provided significant but not complete restoration of function in the ischemic segment. Therefore, in the earliest phase of acute myocardial infarction, retroperfusion might represent a useful temporary support to an otherwise inaccessible jeopardized zone of the heart. Regional retroperfusion may constitute an effective emergency procedure, particularly when the occlusive lesions are diffuse and other medical or surgical emergency procedures are inadvisable, unavailable or ineffective.", "contents": "Diastolic retroperfusion of acutely ischemic myocardium. The effectiveness of coronary venous retroperfusion treatment of an ischemic myocardial segment was assessed by measurements of regional and global myocardial function in 16 dogs. The left anterior descending coronary artery was acutely occluded for 75 minutes. After the first 30 minutes of occlusion, diastolic retroperfusion was instituted for 45 minutes by synchronized pumping of arterial blood from the brachial artery into the anterior interventricular coronary vein. Data collected in the preocclusion control period, during occlusion and the subsequent retroperfusion period included simultaneous measurement os ischemic and border zone myocardial forces, epicardial electrocardiographic S-T segments, intracoronary pressure, coronary blood flow and oxygen pressure (PO2) sampled distal to the site of occlusion. Retroperfusion resulted in significant improvement from the level of regional dysfunction observed after 30 minutes of occlusion: Ischemic zone myocardial force increased 106%, epicardial S-T elevation decreased 46%, normalized peripheral left anterior descending coronary arterial flow increased 50% and distal left anterior descending PO2 decreased 44%. These regional improvements were significant when compared with findings in an untreated series of 12 dogs with 75 minutes occlusion of the left anterior descending coronary artery. Diastolic-augmented coronary venous retroperfusion with arterial blood provided significant but not complete restoration of function in the ischemic segment. Therefore, in the earliest phase of acute myocardial infarction, retroperfusion might represent a useful temporary support to an otherwise inaccessible jeopardized zone of the heart. Regional retroperfusion may constitute an effective emergency procedure, particularly when the occlusive lesions are diffuse and other medical or surgical emergency procedures are inadvisable, unavailable or ineffective."} {"id": "PMID:1258797", "title": "Effects of heparin in large doses on the extent of myocardial ischemia after acute coronary occlusion in the dog.", "content": "Heparin in large doses significantly improved epicardial electrocardiographic findings and preserved myocardial tissue and creatine phosphokinase (CPK) after coronary ligation in the dog. Epicardial S-T segment elevation 15 minutes after occlusion was lowered 84% (from 64.5 + 8.5 [standard error of the mean] to 10.4 +/- 3.0 mv) by heparin infusions of 60,000 units. Myocardial creatine phosphokinase depletion was reduced from 39 to 24% at comparable levels of S-T segment elevation. Histologic evidence of necrosis decreased 32%. It is concluded that heparin can reduce the extent of ischemic injury after acute coronary occlusion in the dog. These results may lend insight into the factors responsible for ischemic injury.", "contents": "Effects of heparin in large doses on the extent of myocardial ischemia after acute coronary occlusion in the dog. Heparin in large doses significantly improved epicardial electrocardiographic findings and preserved myocardial tissue and creatine phosphokinase (CPK) after coronary ligation in the dog. Epicardial S-T segment elevation 15 minutes after occlusion was lowered 84% (from 64.5 + 8.5 [standard error of the mean] to 10.4 +/- 3.0 mv) by heparin infusions of 60,000 units. Myocardial creatine phosphokinase depletion was reduced from 39 to 24% at comparable levels of S-T segment elevation. Histologic evidence of necrosis decreased 32%. It is concluded that heparin can reduce the extent of ischemic injury after acute coronary occlusion in the dog. These results may lend insight into the factors responsible for ischemic injury."} {"id": "PMID:1258798", "title": "Effect of heparin in anticoagulant doses on the electrocardiogram and cardiac enzymes in patients with acute myocardial infarction. A clinical pilot study.", "content": "The effect of heparin in clinical anticoagulant doses on S-T segment and cardiac enzymes was studied in 18 patients with acute myocardial infarction by electrocardiogram and enzyme evaluation 1 hour and 24 hours after initial heparin infusion. Intestinal mucosa heparin was given by infusion, 10,000 units after the admission electrocardiogram, and 5,000 units every 6 hours. Data in the nine control and nine treated patients were statistically similar on admission. The electrocardiograph findings were improved, but not significantly, 1 hour after administration of heparin. At 24 hours of heparin therapy, the S-T deviations were reduced 64% (from 139 +/- 2.1 [standard error of the mean] to 50.5 +/- 1.2 mm); in control patients S-T deviations were reduced 21% (from 109 +/- 1.8 to 86 +/- 0.9 mm (t=2.9, P less than 0.019). At 24% hours electrocardiographic leads with 2 mm or more deviation were reduced 86% in heparin-treated patients and 28% in control subjects. Cardiac enzymes were comparably elevated at 24 and 48 hours in both groups, with no clear trend. It is concluded that heparin in anticoagulant doses reduces the 12 lead electrocardiographic pattern of injury without discernibly modifying cardiac enzymes. The question of heparin efficacy in acute myocardial ischemic injury, reopened by findings with large dose heparin in therapy in dogs and anticoagulant dose in this study, awaits further expanded investigation.", "contents": "Effect of heparin in anticoagulant doses on the electrocardiogram and cardiac enzymes in patients with acute myocardial infarction. A clinical pilot study. The effect of heparin in clinical anticoagulant doses on S-T segment and cardiac enzymes was studied in 18 patients with acute myocardial infarction by electrocardiogram and enzyme evaluation 1 hour and 24 hours after initial heparin infusion. Intestinal mucosa heparin was given by infusion, 10,000 units after the admission electrocardiogram, and 5,000 units every 6 hours. Data in the nine control and nine treated patients were statistically similar on admission. The electrocardiograph findings were improved, but not significantly, 1 hour after administration of heparin. At 24 hours of heparin therapy, the S-T deviations were reduced 64% (from 139 +/- 2.1 [standard error of the mean] to 50.5 +/- 1.2 mm); in control patients S-T deviations were reduced 21% (from 109 +/- 1.8 to 86 +/- 0.9 mm (t=2.9, P less than 0.019). At 24% hours electrocardiographic leads with 2 mm or more deviation were reduced 86% in heparin-treated patients and 28% in control subjects. Cardiac enzymes were comparably elevated at 24 and 48 hours in both groups, with no clear trend. It is concluded that heparin in anticoagulant doses reduces the 12 lead electrocardiographic pattern of injury without discernibly modifying cardiac enzymes. The question of heparin efficacy in acute myocardial ischemic injury, reopened by findings with large dose heparin in therapy in dogs and anticoagulant dose in this study, awaits further expanded investigation."} {"id": "PMID:1258799", "title": "Comparative study of exercise-induced ventricular arrhythmias in normal subjects and patients with documented coronary artery disease.", "content": "The incidence, types and patterns of emergence of treadmill exercise induced ventricular arrhythmias were studied in 482 subjects with and without coronary heart disease. All subjects were free of premature ventricular complexes at rest and were classified into groups on the basis of their clinical status. In Group 1A were 141 patients with chest pain and normal coronary arteriograms and in Group IB 144 age-matched subjects free of clinical evidence of heart disease. Group II consisted of 197 patients with chest pain and arteriographically documented coronary artery disease. Patients in Group IA and II exercised to at least 85% of their predicted maximal heart rate or until chest pain occurred. Subjects in Group IB underwent maximal exercise testing. The total incidence of exercise-induced ventricular arrhythmias was 16% in Group IA, 44% in Group IB and 29% in Group II. However, when exercise heart rate at the time of appearance of ventricular arrhythmias was taken into account the incidence of exercise-induced ventricular arrhythmias up to a heart rate of 130/min was 27% in the patients with documented coronary artery disease (Group II) compared with rates of 9 and 6%, respectively, for Groups IA and IB (P less than 0.001). The incidence rates of multifocal ventricular premature complexes, ventricular tachycardia and ventricular premature complexes at a rate of more than 10/min were also significantly greater at submaximal heart rates in the patients with coronary disease. Patients with three vessel coronary artery disease and abnormal left ventricular wall motion had a significantly greater incidence of exercise-induced ventricular arrhythmias. The incidence of exercise-induced ventricular arrhythmias in patients with coronary disease and a positive S-T segment response was not significantly increased.", "contents": "Comparative study of exercise-induced ventricular arrhythmias in normal subjects and patients with documented coronary artery disease. The incidence, types and patterns of emergence of treadmill exercise induced ventricular arrhythmias were studied in 482 subjects with and without coronary heart disease. All subjects were free of premature ventricular complexes at rest and were classified into groups on the basis of their clinical status. In Group 1A were 141 patients with chest pain and normal coronary arteriograms and in Group IB 144 age-matched subjects free of clinical evidence of heart disease. Group II consisted of 197 patients with chest pain and arteriographically documented coronary artery disease. Patients in Group IA and II exercised to at least 85% of their predicted maximal heart rate or until chest pain occurred. Subjects in Group IB underwent maximal exercise testing. The total incidence of exercise-induced ventricular arrhythmias was 16% in Group IA, 44% in Group IB and 29% in Group II. However, when exercise heart rate at the time of appearance of ventricular arrhythmias was taken into account the incidence of exercise-induced ventricular arrhythmias up to a heart rate of 130/min was 27% in the patients with documented coronary artery disease (Group II) compared with rates of 9 and 6%, respectively, for Groups IA and IB (P less than 0.001). The incidence rates of multifocal ventricular premature complexes, ventricular tachycardia and ventricular premature complexes at a rate of more than 10/min were also significantly greater at submaximal heart rates in the patients with coronary disease. Patients with three vessel coronary artery disease and abnormal left ventricular wall motion had a significantly greater incidence of exercise-induced ventricular arrhythmias. The incidence of exercise-induced ventricular arrhythmias in patients with coronary disease and a positive S-T segment response was not significantly increased."} {"id": "PMID:1258800", "title": "Prevalence and reproducibility of exercise-induced ventricular arrhythmias during maximal exercise testing in normal men.", "content": "The occurrence of ventricular arrhythmias at rest or during ordinary daily activities has been implicated as a risk factor for future coronary-related events and sudden death. However, the clerical significance of exercise-induced ventricular arrhythmias remains uncertain. To assess the prevalence and reproducibility of such arrhythmias, two serial maximal treadmill exercise tests were performed in a study population of 543 male Indian State policemen at an average interval of 2.9 years. Four hundred sixty-two subjects were clinically free of evidence of cardiovascular disease, and 81 had evidence of definite or suspected cardiovascular disease. The prevalence of exercise-induced ventricular arrhythmias during the first test was 30% in men aged 25 to 34 years, 32% in those aged 35 to 44 years and 36% in those aged 45 to 54 years. The prevalence rate in these age groups with repeat testing was 36, 38 and 42%, respectively. These differences were not statistically significant. The group with definite or suspected cardiovascular disease had a greater prevalence of exercise-induced ventricular arrhythmias than normal subjects during both tests but the prevalence rate with repeat testing remained constant. The occurrence of exercise-induced ventricular arrhythmias was reproducible in individual subjects during the second test in 55% of 25 to 34 year olds, 58% of 35 to 44 year olds and 62% of 45 to 54 year olds. Thus, individual reproducibility in two consecutive tests was only slightly greater than reproducibility by chance alone. The group with known or suspected cardiovascular disease demonstrated a trend toward greater reproducibility with repeat testing. Exercise-induced ventricular arrhythmias were not reproducible by type or complexity. The marked variability of exercise-induced ventricular arrhythmias during repeat maximal exercise testing in a clinically normal population appears to negate the usefulness of this finding during a single test as a marker of future cardiovascular disease. Nevertheless, subjects whose arrhythmias were reproducible may form a group destined to manifest clinical cardiovascular disease in long-term follow-up studies.", "contents": "Prevalence and reproducibility of exercise-induced ventricular arrhythmias during maximal exercise testing in normal men. The occurrence of ventricular arrhythmias at rest or during ordinary daily activities has been implicated as a risk factor for future coronary-related events and sudden death. However, the clerical significance of exercise-induced ventricular arrhythmias remains uncertain. To assess the prevalence and reproducibility of such arrhythmias, two serial maximal treadmill exercise tests were performed in a study population of 543 male Indian State policemen at an average interval of 2.9 years. Four hundred sixty-two subjects were clinically free of evidence of cardiovascular disease, and 81 had evidence of definite or suspected cardiovascular disease. The prevalence of exercise-induced ventricular arrhythmias during the first test was 30% in men aged 25 to 34 years, 32% in those aged 35 to 44 years and 36% in those aged 45 to 54 years. The prevalence rate in these age groups with repeat testing was 36, 38 and 42%, respectively. These differences were not statistically significant. The group with definite or suspected cardiovascular disease had a greater prevalence of exercise-induced ventricular arrhythmias than normal subjects during both tests but the prevalence rate with repeat testing remained constant. The occurrence of exercise-induced ventricular arrhythmias was reproducible in individual subjects during the second test in 55% of 25 to 34 year olds, 58% of 35 to 44 year olds and 62% of 45 to 54 year olds. Thus, individual reproducibility in two consecutive tests was only slightly greater than reproducibility by chance alone. The group with known or suspected cardiovascular disease demonstrated a trend toward greater reproducibility with repeat testing. Exercise-induced ventricular arrhythmias were not reproducible by type or complexity. The marked variability of exercise-induced ventricular arrhythmias during repeat maximal exercise testing in a clinically normal population appears to negate the usefulness of this finding during a single test as a marker of future cardiovascular disease. Nevertheless, subjects whose arrhythmias were reproducible may form a group destined to manifest clinical cardiovascular disease in long-term follow-up studies."} {"id": "PMID:1258801", "title": "Beneficial effects of nitroglycerin on abnormal ventricular wall motion at rest and during exercise in patient with previous myocardial infarction.", "content": "The effects of sublingually administered nitroglycerin on segmental left ventricular wall motion determined by videotracking and radiographic left heart size were evaluated at rest and during submaximal hand grip exercise in 10 patients with previous transmural myocardial infarction. After nitroglycerin, diastolic left heart size decreased in the resting state from an average of 49.5 +/- 5.7 (standard deviation) to 47.9 +/- 5.6 mm/m2 body surface area (P less than 0.01) and during handgrip exercise from a mean of 50.7 +/- 590 to 49.1 +/- 4.7 mm/m2 (P less than 0.05). In the resting state, the average maximal velocity of shortening in segments with normal wall motion increased after nitroglycerin from 18.1 +/- 3.0 to 23.5 +/- 5.5 mm/sec (P less than 0.01), whereas during handgrip exercise alone, the velocity of shortening averaged 25.6 +/- 6.9 mm/sec and increased further after nitroglycerin to 30.1 +/- 10.6 mm/sec (P less than 0.05). The effects of nitroglycerin on the average extent of shortening in normal segments were similar. In all 10 patients, there was a decrease in the number of segments with abnormal wall motion. The number of sites with dyssynergy decreased after nitroglycerin from 24 to 15 in the resting state and from 40 to 22 when nitroglycerin was administered before handgrip exercise. Sublingually administered nitroglycerin appears to decrease left heart size, increase the velocity and extent of shortening in normal left ventricular segments and often reduce the extent of left ventricular wall motion abnormalities at rest and during isometric exercise in patients with previous transmural myocardial infarction.", "contents": "Beneficial effects of nitroglycerin on abnormal ventricular wall motion at rest and during exercise in patient with previous myocardial infarction. The effects of sublingually administered nitroglycerin on segmental left ventricular wall motion determined by videotracking and radiographic left heart size were evaluated at rest and during submaximal hand grip exercise in 10 patients with previous transmural myocardial infarction. After nitroglycerin, diastolic left heart size decreased in the resting state from an average of 49.5 +/- 5.7 (standard deviation) to 47.9 +/- 5.6 mm/m2 body surface area (P less than 0.01) and during handgrip exercise from a mean of 50.7 +/- 590 to 49.1 +/- 4.7 mm/m2 (P less than 0.05). In the resting state, the average maximal velocity of shortening in segments with normal wall motion increased after nitroglycerin from 18.1 +/- 3.0 to 23.5 +/- 5.5 mm/sec (P less than 0.01), whereas during handgrip exercise alone, the velocity of shortening averaged 25.6 +/- 6.9 mm/sec and increased further after nitroglycerin to 30.1 +/- 10.6 mm/sec (P less than 0.05). The effects of nitroglycerin on the average extent of shortening in normal segments were similar. In all 10 patients, there was a decrease in the number of segments with abnormal wall motion. The number of sites with dyssynergy decreased after nitroglycerin from 24 to 15 in the resting state and from 40 to 22 when nitroglycerin was administered before handgrip exercise. Sublingually administered nitroglycerin appears to decrease left heart size, increase the velocity and extent of shortening in normal left ventricular segments and often reduce the extent of left ventricular wall motion abnormalities at rest and during isometric exercise in patients with previous transmural myocardial infarction."} {"id": "PMID:1258802", "title": "High blood pressure in children: problems and guidelines for evaluation and treatment.", "content": "Evidence is presented from studies of the authors and of other investigators that primary hypertension is more common in children than was previously thought. Ninety-five percent of 131 asymptomatic children with incidental hypertension were considered to have primary hypertension after investigation for possible causes. The definition of hypertension was based on normal ranges of blood pressure for each age and sex. However, the definition of juvenile hypertension is still unsettled as is the question of treatment. Investigation of the effect of prolonged antihypertensive therapy on growth and development is needed. Primary hypertension in the young makes possible the study of the disease at its inception.", "contents": "High blood pressure in children: problems and guidelines for evaluation and treatment. Evidence is presented from studies of the authors and of other investigators that primary hypertension is more common in children than was previously thought. Ninety-five percent of 131 asymptomatic children with incidental hypertension were considered to have primary hypertension after investigation for possible causes. The definition of hypertension was based on normal ranges of blood pressure for each age and sex. However, the definition of juvenile hypertension is still unsettled as is the question of treatment. Investigation of the effect of prolonged antihypertensive therapy on growth and development is needed. Primary hypertension in the young makes possible the study of the disease at its inception."} {"id": "PMID:1258803", "title": "Big renin: identification, chemical properties and clinical implications.", "content": "Big renin has a greater molecular weight (63,000 versus 43,000) than normal renin, but it shares the characteristic enzymatic and immunologic properties of normal renin. As it exists in the kidney or plasma of a patient, big renin is less active than normal renin, but its enzymatic activity is greatly enhanced by exposure to pH values of 3.0 to 3.6 or by brief incubation with pepsin or trypsin. Use of the terms prorenin and zymogen might be withheld until big renin is shown to exist in normal tissue or plasma and to be converted to normal renin in vivo. To date, big renin has been found in renal tumors and other abnormal kidney tissues as well as in the plasma of patients with renal disorders. The remarkable activation of big renin at pH levels of 3.3 can be used to detect its presence. If a method involving acidification is used to quantitate plasma renin activity of a patient with circulating big renin, the activated plasma renin activity greatly exceeds that measured in plasma maintained at neutral pH. Gel filtration of plasma is used to prove the presence of big renin. When large amounts of big renin are secreted by a renal tumor, hyperfusion may ensue and be cured by removal of the tumor. The secretion of small amounts of big renin does not necessarily result in any physiologic disorder. However, if there is a concomitant diminution or absence of normal renin a state of apparent hyporeninemia exists, as we have observed in diabetic nephropathy; this may be associated with hypoaldosteronism and hyperkalemia. Big renin does not appear to respond to physiologic changes that stimulate or suppress normal plasma renin activity. The finding of big renin may indicate the presence of certain renin-secreting renal tumors or other renal disorders, especially diabetic nephropathy.", "contents": "Big renin: identification, chemical properties and clinical implications. Big renin has a greater molecular weight (63,000 versus 43,000) than normal renin, but it shares the characteristic enzymatic and immunologic properties of normal renin. As it exists in the kidney or plasma of a patient, big renin is less active than normal renin, but its enzymatic activity is greatly enhanced by exposure to pH values of 3.0 to 3.6 or by brief incubation with pepsin or trypsin. Use of the terms prorenin and zymogen might be withheld until big renin is shown to exist in normal tissue or plasma and to be converted to normal renin in vivo. To date, big renin has been found in renal tumors and other abnormal kidney tissues as well as in the plasma of patients with renal disorders. The remarkable activation of big renin at pH levels of 3.3 can be used to detect its presence. If a method involving acidification is used to quantitate plasma renin activity of a patient with circulating big renin, the activated plasma renin activity greatly exceeds that measured in plasma maintained at neutral pH. Gel filtration of plasma is used to prove the presence of big renin. When large amounts of big renin are secreted by a renal tumor, hyperfusion may ensue and be cured by removal of the tumor. The secretion of small amounts of big renin does not necessarily result in any physiologic disorder. However, if there is a concomitant diminution or absence of normal renin a state of apparent hyporeninemia exists, as we have observed in diabetic nephropathy; this may be associated with hypoaldosteronism and hyperkalemia. Big renin does not appear to respond to physiologic changes that stimulate or suppress normal plasma renin activity. The finding of big renin may indicate the presence of certain renin-secreting renal tumors or other renal disorders, especially diabetic nephropathy."} {"id": "PMID:1258804", "title": "Light and electron microscopic observations on hydrocortisone-induced cleft palate in hamsters.", "content": "Palatal histogenesis in hydrocortisone-treated hamster fetuses was studied by both light and electron microscopy. At an early stage in the hydrocortisone-affected fetuses, when the palatal shelves hung vertically on either side of the tongue, necortic changes could be seen in some of the basal epithelial cells which lay adjacent to the fragmented basal lamina. The normal looking cells lay on an intact basal lamina and were attached to the contiguous necrotic cells by desmosomes. With horizontal reorientation of the palatal shelves and their approach to the midline, cellular necrosis and fragmentation of the basal lamina increased. When compared with normal cells, the hydrocortisone-affected ones were seen to be lighter, to contain fewer ribosomes and no lysosomes. At a later stage, when midline palatal fusion was lacking, the epithelium underwent stratification and keratinization while the necrotic debris was removed by mesenchymal macrophages. It appears that the normal process of protein synthesis is inhibited following hydrocortisone administration and that this, in turn, during palatogenesis, disrupts normal cellular differentiation and the integrity of the basal lamina, which are associated with the production of a cleft palate.", "contents": "Light and electron microscopic observations on hydrocortisone-induced cleft palate in hamsters. Palatal histogenesis in hydrocortisone-treated hamster fetuses was studied by both light and electron microscopy. At an early stage in the hydrocortisone-affected fetuses, when the palatal shelves hung vertically on either side of the tongue, necortic changes could be seen in some of the basal epithelial cells which lay adjacent to the fragmented basal lamina. The normal looking cells lay on an intact basal lamina and were attached to the contiguous necrotic cells by desmosomes. With horizontal reorientation of the palatal shelves and their approach to the midline, cellular necrosis and fragmentation of the basal lamina increased. When compared with normal cells, the hydrocortisone-affected ones were seen to be lighter, to contain fewer ribosomes and no lysosomes. At a later stage, when midline palatal fusion was lacking, the epithelium underwent stratification and keratinization while the necrotic debris was removed by mesenchymal macrophages. It appears that the normal process of protein synthesis is inhibited following hydrocortisone administration and that this, in turn, during palatogenesis, disrupts normal cellular differentiation and the integrity of the basal lamina, which are associated with the production of a cleft palate."} {"id": "PMID:1258805", "title": "The transmural passage of blood cells into myeloid sinusoids and the entry of platelets into the sinusoidal circulation; a scanning electron microscopic investigation.", "content": "Scanning electron microscopic observations of rat bone marrow reveal that the sinusoidal wall is continuous and has no permanent patent apertures allowing free communication between the extravascular and intravascular myeloid compartments. Blood cells migrate into the sinusoids by perforating the endothelial cell body. Platelets are derived from long intrasinusoidal \"proplatelet\" processes which originate from the cell body of extravascularly located megakaryocytes. Proplatelet processes frequently occur in clusters, with the probability that all processes in a cluster arise from a single megakaryocyte. The release of platelets into the circulation may be initiated by local constriction along these processes, at which places either individual platelets or larger segments of proplatelet cytoplasm are pinched off. The larger segments may subsequently undergo further fragmentation into individual platelets.", "contents": "The transmural passage of blood cells into myeloid sinusoids and the entry of platelets into the sinusoidal circulation; a scanning electron microscopic investigation. Scanning electron microscopic observations of rat bone marrow reveal that the sinusoidal wall is continuous and has no permanent patent apertures allowing free communication between the extravascular and intravascular myeloid compartments. Blood cells migrate into the sinusoids by perforating the endothelial cell body. Platelets are derived from long intrasinusoidal \"proplatelet\" processes which originate from the cell body of extravascularly located megakaryocytes. Proplatelet processes frequently occur in clusters, with the probability that all processes in a cluster arise from a single megakaryocyte. The release of platelets into the circulation may be initiated by local constriction along these processes, at which places either individual platelets or larger segments of proplatelet cytoplasm are pinched off. The larger segments may subsequently undergo further fragmentation into individual platelets."} {"id": "PMID:1258806", "title": "Movement of entire cell populations during renewal of the rat incisor as shown by radoioautography after labeling with 3H-thymidine. The concept of a continuously differentiating cross-sectional segment. (With an appendix on the development of the periodontal ligament).", "content": "Renewal of the rat incisor was studied in three dimensions by employing a serial cross-sectioning technique to locate the boundary between labeled and unlabeled cells in the enamel organ and odontoblast layer at various times after a single injection of 3H-thymidine. This boundary, or leading edge of the front of labeling, was graphically illustrated through point-plotting reconstruction of the labial surface of the incisor. At one hour after the injection of 3H-thymidine the front of labeled ameloblasts was located within the presecretory zone related to early predentin secretion. This front formed a \"C\"-shaped curve stretching across the labial surface of the tooth from the lateral to the mesial cemento-enamel junction. The \"C\" was open anteriorly and the lateral arm extended almost twice as far incisally as the mesial arm. The edge of the front of labeled odontoblasts was positioned apical to and parallel with this \"C\"-shaped curve. The morphological appearance of all cells along each respective front was found to be similar. As the fronts of labeled ameloblasts and labeled odontoblasts moved forward with the erupting incisor, the cells along these fronts differentiated simultaneously and subsequently formed enamel and dentin. Throughout this movement the distance between fixed points along the leading edge of the front of labeled ameloblasts, and its positional relationship to the front of labeled odontoblasts, did not change appreciably. This indicated that cells of the tooth were being carried incisally at a uniform speed. It was concluded that renewal in the rat incisor consists of the generation by the bulbous part of the odontogenic organ of epithelial \"U\"-shaped cross-sectional segments which enclose a core of pulp. As this segment is transported towards the gingival margin, cellular differentiation and subsequent formation of hard tissue is seen to begin at the central labial side of the segment and to progress in a mesial and lateral direction towards the lingual side. In the process, the limits of the enamel organ at the mesial and lateral cemento-enamel junctions are established and the entire circumference of the segment is eventually enclosed by a rim of dentin.", "contents": "Movement of entire cell populations during renewal of the rat incisor as shown by radoioautography after labeling with 3H-thymidine. The concept of a continuously differentiating cross-sectional segment. (With an appendix on the development of the periodontal ligament). Renewal of the rat incisor was studied in three dimensions by employing a serial cross-sectioning technique to locate the boundary between labeled and unlabeled cells in the enamel organ and odontoblast layer at various times after a single injection of 3H-thymidine. This boundary, or leading edge of the front of labeling, was graphically illustrated through point-plotting reconstruction of the labial surface of the incisor. At one hour after the injection of 3H-thymidine the front of labeled ameloblasts was located within the presecretory zone related to early predentin secretion. This front formed a \"C\"-shaped curve stretching across the labial surface of the tooth from the lateral to the mesial cemento-enamel junction. The \"C\" was open anteriorly and the lateral arm extended almost twice as far incisally as the mesial arm. The edge of the front of labeled odontoblasts was positioned apical to and parallel with this \"C\"-shaped curve. The morphological appearance of all cells along each respective front was found to be similar. As the fronts of labeled ameloblasts and labeled odontoblasts moved forward with the erupting incisor, the cells along these fronts differentiated simultaneously and subsequently formed enamel and dentin. Throughout this movement the distance between fixed points along the leading edge of the front of labeled ameloblasts, and its positional relationship to the front of labeled odontoblasts, did not change appreciably. This indicated that cells of the tooth were being carried incisally at a uniform speed. It was concluded that renewal in the rat incisor consists of the generation by the bulbous part of the odontogenic organ of epithelial \"U\"-shaped cross-sectional segments which enclose a core of pulp. As this segment is transported towards the gingival margin, cellular differentiation and subsequent formation of hard tissue is seen to begin at the central labial side of the segment and to progress in a mesial and lateral direction towards the lingual side. In the process, the limits of the enamel organ at the mesial and lateral cemento-enamel junctions are established and the entire circumference of the segment is eventually enclosed by a rim of dentin."} {"id": "PMID:1258817", "title": "Sugar as a vehicle for iron fortification: further studies.", "content": "The data presented confirm the advantages of sugar as a vehicle for iron fortification over other vehicles used in the past. The absorption comparison between ferric and ferrous salts added to sugar demonstrated that Fe(III)-EDTA Complex and ferrous sulfate exhibited the highest absorption, while ferric ammonium citrate was poorly absorbed. It was also found that Fe(III)-EDTA reacts slowly with the tannin contained in tea; the color of the tea changes slightly in the first 2 hr after the addition of the fortified sugar. Iron absorption of sugar fortified with ferrous sulfate was tested in seven beverages. The mean absorption ratio from fortified sugar given with beverages to reference dose of iron ascorbate ranged between 0.42 and 0.70, that is, more than 4 times the absorption from fortified sugar when it is administered with a meal containing one or more vegetals. An absorption of between 0.25 and 0.80 mg of iron/soft drink sugar fortified with 3 mg of iron as ferrous sulfate can be expected in subjects with various degrees of iron deficiency. Thus, two soft drinks per day between meals would be enough to meet the iron requirement in more than 95% of menstruating women, even though the daily iron absorption from the diet is about 0.8 to 1.0 mg.", "contents": "Sugar as a vehicle for iron fortification: further studies. The data presented confirm the advantages of sugar as a vehicle for iron fortification over other vehicles used in the past. The absorption comparison between ferric and ferrous salts added to sugar demonstrated that Fe(III)-EDTA Complex and ferrous sulfate exhibited the highest absorption, while ferric ammonium citrate was poorly absorbed. It was also found that Fe(III)-EDTA reacts slowly with the tannin contained in tea; the color of the tea changes slightly in the first 2 hr after the addition of the fortified sugar. Iron absorption of sugar fortified with ferrous sulfate was tested in seven beverages. The mean absorption ratio from fortified sugar given with beverages to reference dose of iron ascorbate ranged between 0.42 and 0.70, that is, more than 4 times the absorption from fortified sugar when it is administered with a meal containing one or more vegetals. An absorption of between 0.25 and 0.80 mg of iron/soft drink sugar fortified with 3 mg of iron as ferrous sulfate can be expected in subjects with various degrees of iron deficiency. Thus, two soft drinks per day between meals would be enough to meet the iron requirement in more than 95% of menstruating women, even though the daily iron absorption from the diet is about 0.8 to 1.0 mg."} {"id": "PMID:1258818", "title": "Human protein requirements: the effect of variations in energy intake within the maintenance range.", "content": "Protein requirement studies in man generally avoid deficient dietary energy intakes because they decrease the efficiency of nitrogen utilization, but the opposite effect of excess dietary energy is usually overlooked. Four young men were fed the 1973 FAO/WHO safe level of egg protein (0.57 g/kg) at several levels of dietary energy. The data indicate that a significant proportion of the population may require excess energy intakes to maintain nitrogen balance at this level of dietary protein. Variations in dietary energy ranging from submaintenance to 15 to 20% above estimated maintenance needs altered net egg protein utilization in three subjects by 2 to 4.5 units/kcal per kg body wt.", "contents": "Human protein requirements: the effect of variations in energy intake within the maintenance range. Protein requirement studies in man generally avoid deficient dietary energy intakes because they decrease the efficiency of nitrogen utilization, but the opposite effect of excess dietary energy is usually overlooked. Four young men were fed the 1973 FAO/WHO safe level of egg protein (0.57 g/kg) at several levels of dietary energy. The data indicate that a significant proportion of the population may require excess energy intakes to maintain nitrogen balance at this level of dietary protein. Variations in dietary energy ranging from submaintenance to 15 to 20% above estimated maintenance needs altered net egg protein utilization in three subjects by 2 to 4.5 units/kcal per kg body wt."} {"id": "PMID:1258819", "title": "A nomograph method for assessing body weight.", "content": "The ratio of weight/height emerges from varied epidemiological studies as the most generally useful index of relative body mass in adults. The authors present a nomograph to facilitate use of this relationship in clinical situations. While showing the range of weight given as desirable in life insurance studies, the scale expresses relative weight as a continuous variable. This method encourages use of clinical judgment in interpreting \"overweight\" and \"underweight\" and in accounting for muscular and skeletal contributions to measured mass.", "contents": "A nomograph method for assessing body weight. The ratio of weight/height emerges from varied epidemiological studies as the most generally useful index of relative body mass in adults. The authors present a nomograph to facilitate use of this relationship in clinical situations. While showing the range of weight given as desirable in life insurance studies, the scale expresses relative weight as a continuous variable. This method encourages use of clinical judgment in interpreting \"overweight\" and \"underweight\" and in accounting for muscular and skeletal contributions to measured mass."} {"id": "PMID:1258820", "title": "Nutrition, infant behavior, and maternal characteristics: a pilot study in West Bengal, India.", "content": "Free activities and mother-child interaction in a standard setting were observed among undernourished and well-nourished children between the ages of 7 and 18 months in West Bengal. The undernourished boys showed less vigor in play activity, less attachment behavior toward the mother, especially in interaction across a distance, and maintained close physical contact with her more frequently than did the well-nourished boys. The mothers of the undernourished boys had lower scores in four of six measures of maternal behavior. Correlations between child and maternal scores revealed a high reciprocity in mother-child interaction for the well-nourished boys, but a lack of reciprocity for the undernourished boys. The developmental quotient and activity scores of the well- and undernourished boys were not different. However, the correlations between these and the maternal scores showed a divergent pattern of relationships for the two nutritional groups.", "contents": "Nutrition, infant behavior, and maternal characteristics: a pilot study in West Bengal, India. Free activities and mother-child interaction in a standard setting were observed among undernourished and well-nourished children between the ages of 7 and 18 months in West Bengal. The undernourished boys showed less vigor in play activity, less attachment behavior toward the mother, especially in interaction across a distance, and maintained close physical contact with her more frequently than did the well-nourished boys. The mothers of the undernourished boys had lower scores in four of six measures of maternal behavior. Correlations between child and maternal scores revealed a high reciprocity in mother-child interaction for the well-nourished boys, but a lack of reciprocity for the undernourished boys. The developmental quotient and activity scores of the well- and undernourished boys were not different. However, the correlations between these and the maternal scores showed a divergent pattern of relationships for the two nutritional groups."} {"id": "PMID:1258821", "title": "Pulmonary vascular disease in systemic lupus erythematosus.", "content": "The pulmonary vascular changes in systemic lupus erythematosus (SLE) have been investigated from 20 autopsies performed at the Mount Sinai Hospiral from 1964 to 1973. Acute lesions included fibrinoid necrosis and vasculitis. Chronic lesions consisted of intimal fibrosis, medial hypertrophy, alteration of elastic laminae, periadventitial fibrosis, and, in one case, aneruysmal dilatation. These changes were found variously in arterioles, arteries and veins. The fibrotic and occlusive vascular lesions may account for the syndrome of \"unexplained breathlessness\" that occurs in SLE. These lesions may progress in certain individuals to overt pulmonary hypertension; the concept of coexisting primary pulmonary hypertension and SLE should be re-examined.", "contents": "Pulmonary vascular disease in systemic lupus erythematosus. The pulmonary vascular changes in systemic lupus erythematosus (SLE) have been investigated from 20 autopsies performed at the Mount Sinai Hospiral from 1964 to 1973. Acute lesions included fibrinoid necrosis and vasculitis. Chronic lesions consisted of intimal fibrosis, medial hypertrophy, alteration of elastic laminae, periadventitial fibrosis, and, in one case, aneruysmal dilatation. These changes were found variously in arterioles, arteries and veins. The fibrotic and occlusive vascular lesions may account for the syndrome of \"unexplained breathlessness\" that occurs in SLE. These lesions may progress in certain individuals to overt pulmonary hypertension; the concept of coexisting primary pulmonary hypertension and SLE should be re-examined."} {"id": "PMID:1258822", "title": "Glomerulonephritis due to Staphylococcus aureus antigen.", "content": "Staphylococcus aureus antigen was identified within the glomeruli of a patient with acute bacterial endocarditis and diffuse glomerulonephritis. Routine immunofluorescence had revealed only granular deposits of complement (C3). C3 activator and C4 were not present. Direct immunofluorescence studies with a specific anti-Staphylococcus aureus conjugate were positive. Electron microscopy showed subepithelial and intramembranous electron-dense deposits. Eluates of the kidney did not contain anti-S. aureus antibody. The absence of immunoglobin suggests that the toxic action of S. aureus antigens may activate complement and cause glomerular injury and that immune complexes are not essential for the production of glomerulonephritis in this entity.", "contents": "Glomerulonephritis due to Staphylococcus aureus antigen. Staphylococcus aureus antigen was identified within the glomeruli of a patient with acute bacterial endocarditis and diffuse glomerulonephritis. Routine immunofluorescence had revealed only granular deposits of complement (C3). C3 activator and C4 were not present. Direct immunofluorescence studies with a specific anti-Staphylococcus aureus conjugate were positive. Electron microscopy showed subepithelial and intramembranous electron-dense deposits. Eluates of the kidney did not contain anti-S. aureus antibody. The absence of immunoglobin suggests that the toxic action of S. aureus antigens may activate complement and cause glomerular injury and that immune complexes are not essential for the production of glomerulonephritis in this entity."} {"id": "PMID:1258823", "title": "Cystosarcoma phyllodes with liposarcomatous stroma.", "content": "A case of cystosarcoma phyllodes with liposarcomatous stroma is presented. Electron-microscopic study revealed lipid-containing tumor cells admixed with other mesenchymal cells devoid of fat, correlating well with the light-microscopic findings. The literature is briefly reviewed.", "contents": "Cystosarcoma phyllodes with liposarcomatous stroma. A case of cystosarcoma phyllodes with liposarcomatous stroma is presented. Electron-microscopic study revealed lipid-containing tumor cells admixed with other mesenchymal cells devoid of fat, correlating well with the light-microscopic findings. The literature is briefly reviewed."} {"id": "PMID:1258824", "title": "Ultrastructural observations on a follicular carcinoma of the thyroid gland.", "content": "Electron microscopic studies were performed on a follicular carcinoma removed from a 31-year-old woman. The tumor was poorly differentiated and inoperable but distinctly follicular in pattern. Ultrastructurally, the neoplasm had many of the features of papillary carcinoma, follicular adenoma, and anaplastic carcinoma. Due to the presence of secretory granules it even somewhat resembled medullary carcinoma, but the granules were distinctly larger, and the production of amyloid was definitely excluded.", "contents": "Ultrastructural observations on a follicular carcinoma of the thyroid gland. Electron microscopic studies were performed on a follicular carcinoma removed from a 31-year-old woman. The tumor was poorly differentiated and inoperable but distinctly follicular in pattern. Ultrastructurally, the neoplasm had many of the features of papillary carcinoma, follicular adenoma, and anaplastic carcinoma. Due to the presence of secretory granules it even somewhat resembled medullary carcinoma, but the granules were distinctly larger, and the production of amyloid was definitely excluded."} {"id": "PMID:1258825", "title": "Pancytopenia associated with a granulosa-cell tumor of the ovary. Report of a case.", "content": "An unusual case of pancytopenia associated with a granulosa-cell tumor of the ovary in a 44-year-old woman is reported. Initially the patient was thought to have the rare, but well recognized, syndrome of hemolytic anemia complicating an ovarian tumor. However, laboratory studies and clinical follow-up ruled out hyperhemolysis and documented a condition of bone-marrow failure. Excision of the massive tumor was followed by hematologic recovery, which has now lasted more than a year and a half.", "contents": "Pancytopenia associated with a granulosa-cell tumor of the ovary. Report of a case. An unusual case of pancytopenia associated with a granulosa-cell tumor of the ovary in a 44-year-old woman is reported. Initially the patient was thought to have the rare, but well recognized, syndrome of hemolytic anemia complicating an ovarian tumor. However, laboratory studies and clinical follow-up ruled out hyperhemolysis and documented a condition of bone-marrow failure. Excision of the massive tumor was followed by hematologic recovery, which has now lasted more than a year and a half."} {"id": "PMID:1258826", "title": "The detection of CPK1 (BB) in serum. A summary of sixteen cases.", "content": "CPK1 (BB) was detected in the sera of 16 patients during an 18-month period. Eight of 16 had undergone cardiopulmonary resuscitation for cardiac arrest or ventricular fibrillation. Four of these eight had clinical or EEG evidence of cerebral damage. The brain is the most probable source for CPK1 in these eight cases. Two others had proven brain damage, one a massive cerebral infarct and one a traumatic cerebral hematoma requiring craniotomy. One patient had membranous enterocolitis, suggesting an intestinal source for CPK1. The source for the CPK1 in the other five cases was much less obvious, but was probably the brain.", "contents": "The detection of CPK1 (BB) in serum. A summary of sixteen cases. CPK1 (BB) was detected in the sera of 16 patients during an 18-month period. Eight of 16 had undergone cardiopulmonary resuscitation for cardiac arrest or ventricular fibrillation. Four of these eight had clinical or EEG evidence of cerebral damage. The brain is the most probable source for CPK1 in these eight cases. Two others had proven brain damage, one a massive cerebral infarct and one a traumatic cerebral hematoma requiring craniotomy. One patient had membranous enterocolitis, suggesting an intestinal source for CPK1. The source for the CPK1 in the other five cases was much less obvious, but was probably the brain."} {"id": "PMID:1258827", "title": "A new combined thyroid hormone index based on thyroxine, triiodothyronine and resin uptake.", "content": "A new thyroid hormone index, based on measurements of thyroxine (T4), triiodothyronine (T3) and resin uptake (RT3U), is proposed. In contrast to previous thyroid hormone indices, it incorporates both T3 and T4 measurements. This combined thyroid hormone index appears to have superior predictive value in terms of clinical correlation with thyroid disease.", "contents": "A new combined thyroid hormone index based on thyroxine, triiodothyronine and resin uptake. A new thyroid hormone index, based on measurements of thyroxine (T4), triiodothyronine (T3) and resin uptake (RT3U), is proposed. In contrast to previous thyroid hormone indices, it incorporates both T3 and T4 measurements. This combined thyroid hormone index appears to have superior predictive value in terms of clinical correlation with thyroid disease."} {"id": "PMID:1258828", "title": "Measurement of DNA antibodies.", "content": "Modifications of the standard Farr technic for assaying DNA antibodies are presented; these result in improved separation of normals from abnormals, enhanced reproducibility, and simplicity of performance. The use of 0.4 M borate buffer extends the range of the assay, while a 0.1 M buffer aids differentiation when equivocal results are obtained. Centrifugation of vials prior to counting improves the reproducibility by approximately 3%. Polyethylene glycol, at a final concentration of 6 Gm. per 100 ml., can be substituted for ammonium sulfate, with some advantages.", "contents": "Measurement of DNA antibodies. Modifications of the standard Farr technic for assaying DNA antibodies are presented; these result in improved separation of normals from abnormals, enhanced reproducibility, and simplicity of performance. The use of 0.4 M borate buffer extends the range of the assay, while a 0.1 M buffer aids differentiation when equivocal results are obtained. Centrifugation of vials prior to counting improves the reproducibility by approximately 3%. Polyethylene glycol, at a final concentration of 6 Gm. per 100 ml., can be substituted for ammonium sulfate, with some advantages."} {"id": "PMID:1258829", "title": "Urinary loss of clotting factors due to hereditary membranous glomerulopathy.", "content": "Severe plasma deficiencies of clotting factors IX and XII developed in a 59-year-old woman with a nephrotic syndrome secondary to a laminated membranous glomerulopathy. Both these clotting factors were subsequently identified in the patient's urine. Chromatographic analysis of the urine revealed that the bulk of clotting activity attributed to factors IX ann XII was in early eluting gel filtration fractions containing predominately alpha-2 globulin and albumin. The unprecedented finding of two coagulation proteins in the urine is attributed to the marked proteinuria present in this case.", "contents": "Urinary loss of clotting factors due to hereditary membranous glomerulopathy. Severe plasma deficiencies of clotting factors IX and XII developed in a 59-year-old woman with a nephrotic syndrome secondary to a laminated membranous glomerulopathy. Both these clotting factors were subsequently identified in the patient's urine. Chromatographic analysis of the urine revealed that the bulk of clotting activity attributed to factors IX ann XII was in early eluting gel filtration fractions containing predominately alpha-2 globulin and albumin. The unprecedented finding of two coagulation proteins in the urine is attributed to the marked proteinuria present in this case."} {"id": "PMID:1258830", "title": "Antithrombin and heparin antithrombin patterns in pre-thrombosis and thrombosis.", "content": "An antithrombin assay (AA) and an antithrombin assay modified by the addition of heparin (H-AA) were performed using sera from healthy subjects, patients predisposed to thrombosis, and patients with thromboembolic disease. Characteristic AA, and H-AA patterns were found in each group. Normal controls and four of 39 \"pill\" patients (10%) had normal AA and H-AA findings (Pattern A). Normal AA, with \"decreasing\" H-AA (Pattern B) was found in sera of 31 of 39 \"pill\" patients (80%) and three patients who had non-embolic arterial occlusive disease. Low AA and \"decreasing\" H-AA (Pattern C) occurred in sera of four \"pill\"-takers (10%) and one patient who had an arterial embolus. Low AA and low H-AA (Pattern D) developed in sera of eight patients with thrombophlebitis and seven patients with pulmonary embolus. It is concluded that the AA and H-AA assays help to identify thrombosis-prone (Pattern C) and thrombotic (Pattern D) individuals for whom antiplatelet (aspirin; dipyridamole) or anticoagulant therapy might be beneficial.", "contents": "Antithrombin and heparin antithrombin patterns in pre-thrombosis and thrombosis. An antithrombin assay (AA) and an antithrombin assay modified by the addition of heparin (H-AA) were performed using sera from healthy subjects, patients predisposed to thrombosis, and patients with thromboembolic disease. Characteristic AA, and H-AA patterns were found in each group. Normal controls and four of 39 \"pill\" patients (10%) had normal AA and H-AA findings (Pattern A). Normal AA, with \"decreasing\" H-AA (Pattern B) was found in sera of 31 of 39 \"pill\" patients (80%) and three patients who had non-embolic arterial occlusive disease. Low AA and \"decreasing\" H-AA (Pattern C) occurred in sera of four \"pill\"-takers (10%) and one patient who had an arterial embolus. Low AA and low H-AA (Pattern D) developed in sera of eight patients with thrombophlebitis and seven patients with pulmonary embolus. It is concluded that the AA and H-AA assays help to identify thrombosis-prone (Pattern C) and thrombotic (Pattern D) individuals for whom antiplatelet (aspirin; dipyridamole) or anticoagulant therapy might be beneficial."} {"id": "PMID:1258831", "title": "Blood recalcification time. A simple and reliable test to monitor heparin therapy.", "content": "The applicability of blood recalcification time as a laboratory test to assess and thereby regulate heparin anticoagulation was evaluated. Normal values for blood recalcification time ranged from 65 to 135 seconds, with a mean and standard deviation of 99 and 12 seconds, respectively. Duplicate determinations showed a mean variation of 5%. Blood recalcification times increased as a linear function of increasing heparin concentrations in vitro. Comparison with whole-blood clotting times revealed reasonably good correlation between the two tests. For whole-blood clotting times of 20 to 45 minutes the corresponding blood recalcification times were 142 to 212 seconds. The therapeutic range is often considered to be twice the normal range (130-270 seconds). In-vivo study revealed the peak blood recalcification time in the first sample collected 30 minutes after heparin injection, and a progressive decline thereafter to the pre-injection level during the subsequent 4 hours. The blood recalcification time is a simple, precise and clinically useful test to monitor heparin therapy.", "contents": "Blood recalcification time. A simple and reliable test to monitor heparin therapy. The applicability of blood recalcification time as a laboratory test to assess and thereby regulate heparin anticoagulation was evaluated. Normal values for blood recalcification time ranged from 65 to 135 seconds, with a mean and standard deviation of 99 and 12 seconds, respectively. Duplicate determinations showed a mean variation of 5%. Blood recalcification times increased as a linear function of increasing heparin concentrations in vitro. Comparison with whole-blood clotting times revealed reasonably good correlation between the two tests. For whole-blood clotting times of 20 to 45 minutes the corresponding blood recalcification times were 142 to 212 seconds. The therapeutic range is often considered to be twice the normal range (130-270 seconds). In-vivo study revealed the peak blood recalcification time in the first sample collected 30 minutes after heparin injection, and a progressive decline thereafter to the pre-injection level during the subsequent 4 hours. The blood recalcification time is a simple, precise and clinically useful test to monitor heparin therapy."} {"id": "PMID:1258835", "title": "Frontometaphyseal Dysplasia. Evidence for dominant inheritance.", "content": "A 10-year-old boy with mixed bilateral hearing loss and unusual facies was found to have frontometaphyseal dysplasia. He has prominent supraorbital ridges, height-span disproportion, dental abnormalities, thick clavicles, pectus excavatum, winged scapulae, joint contractures, and generalized muscular underdevelopment. Roentgenograms show supraorbital hyperostosis, antegonial notching of the mandible, flared ilia, contraction of the midpelvis, flattened vertebrae, deformities of the ribs posteriorly, flared metaphyses of the long tubular bones, and greatly widened and elongated metacarpals, metatarsals, and phalanges. His mother has prominent supraorbital ridges, distinct scoliosis, contractures of the fifth fingers, and conductive hearing loss. She also has many of the roentgenographic features of frontometaphyseal dysplasia. Frontometaphyseal dysplasia in a mother and son strongly suggests a dominant mode of inheritance.", "contents": "Frontometaphyseal Dysplasia. Evidence for dominant inheritance. A 10-year-old boy with mixed bilateral hearing loss and unusual facies was found to have frontometaphyseal dysplasia. He has prominent supraorbital ridges, height-span disproportion, dental abnormalities, thick clavicles, pectus excavatum, winged scapulae, joint contractures, and generalized muscular underdevelopment. Roentgenograms show supraorbital hyperostosis, antegonial notching of the mandible, flared ilia, contraction of the midpelvis, flattened vertebrae, deformities of the ribs posteriorly, flared metaphyses of the long tubular bones, and greatly widened and elongated metacarpals, metatarsals, and phalanges. His mother has prominent supraorbital ridges, distinct scoliosis, contractures of the fifth fingers, and conductive hearing loss. She also has many of the roentgenographic features of frontometaphyseal dysplasia. Frontometaphyseal dysplasia in a mother and son strongly suggests a dominant mode of inheritance."} {"id": "PMID:1258836", "title": "A considered approach to sterilization of mentally retarded youth.", "content": "A protocol of response to families requesting sterilization for retarded youths was developed, utilizing the multidisciplinary approach already structured in a project of sex education and family planning for handicapped juveniles. We operated on 20 patients over a 3 1/2 -year period. Specific criteria for sterilization eligibility were applied, based on medical diagnosis and psychometric and psychosocial maturity evaluation. Long-term follow-up indicates parental satisfaction, improved school attendance for patients after hysterectomy who were previously unable to cope with menstrual hygiene, and no postoperative depression or increase of sexual activity or sexual exploitation.", "contents": "A considered approach to sterilization of mentally retarded youth. A protocol of response to families requesting sterilization for retarded youths was developed, utilizing the multidisciplinary approach already structured in a project of sex education and family planning for handicapped juveniles. We operated on 20 patients over a 3 1/2 -year period. Specific criteria for sterilization eligibility were applied, based on medical diagnosis and psychometric and psychosocial maturity evaluation. Long-term follow-up indicates parental satisfaction, improved school attendance for patients after hysterectomy who were previously unable to cope with menstrual hygiene, and no postoperative depression or increase of sexual activity or sexual exploitation."} {"id": "PMID:1258838", "title": "Acute encephalopathy in siblings. Reye syndrome vs salicylate intoxication.", "content": "Siblings, aged 9 and 7 years, had simultaneous onset of vomiting, disorientation, ataxia, and coma. Both children had prodromal symptoms of upper respiratory tract infections, and had been treated with large doses of aspirin. Laboratory data showed evidence of hepatocellular dysfunction, with an elevated serum ammonia level in one patient; salicylate levels were 50 and 44 mg/100 ml. The child who died had autopsy evidence of cerebral edema and fatty liver. The difficulty in clinically differentiating Reye syndrome from salicylate intoxication is discussed.", "contents": "Acute encephalopathy in siblings. Reye syndrome vs salicylate intoxication. Siblings, aged 9 and 7 years, had simultaneous onset of vomiting, disorientation, ataxia, and coma. Both children had prodromal symptoms of upper respiratory tract infections, and had been treated with large doses of aspirin. Laboratory data showed evidence of hepatocellular dysfunction, with an elevated serum ammonia level in one patient; salicylate levels were 50 and 44 mg/100 ml. The child who died had autopsy evidence of cerebral edema and fatty liver. The difficulty in clinically differentiating Reye syndrome from salicylate intoxication is discussed."} {"id": "PMID:1258839", "title": "Bronchial adenoma in childhood. Two case reports and review of literature.", "content": "A review of the literature discloses 56 cases of bronchial adenoma in children under the age of 16 years; we now report two additional cases. The diagnosis of bronchial adenoma in children is often delayed due to erroneous interpretation of the secondary manifestations of pneumonitis, fever, or wheezing. These tumors should be considered potentially malignant, since local invasion and metastasis have been reported in this age group. Treatment is by thoracotomy with total excision of the lesion.", "contents": "Bronchial adenoma in childhood. Two case reports and review of literature. A review of the literature discloses 56 cases of bronchial adenoma in children under the age of 16 years; we now report two additional cases. The diagnosis of bronchial adenoma in children is often delayed due to erroneous interpretation of the secondary manifestations of pneumonitis, fever, or wheezing. These tumors should be considered potentially malignant, since local invasion and metastasis have been reported in this age group. Treatment is by thoracotomy with total excision of the lesion."} {"id": "PMID:1258840", "title": "Abnormal collagen in ataxia telangiectasia.", "content": "Ataxia telangiectasia has been associated with varying clinical and laboratory abnormalities of the cutaneous, immune, neurological, and endocrine systems. Recently, a primary defect in tissue differentiation has been proposed as a probable cause of the disease. The presence of biochemically abnormal collagen in the skin of two siblings with the disease may further support this hypothesis.", "contents": "Abnormal collagen in ataxia telangiectasia. Ataxia telangiectasia has been associated with varying clinical and laboratory abnormalities of the cutaneous, immune, neurological, and endocrine systems. Recently, a primary defect in tissue differentiation has been proposed as a probable cause of the disease. The presence of biochemically abnormal collagen in the skin of two siblings with the disease may further support this hypothesis."} {"id": "PMID:1258841", "title": "Partial DiGeorge syndrome with substantial cell-mediated immunity.", "content": "Results of studies on two male infants with incomplete expression of the DiGeorge syndrome are analyzed. Both infants demonstrated neonatal tetany with hypoparathyroidism, cardiovascular anomalies, and absence of a thymus shadow on roentgenographic examination. Some degree of cellular immunity was present in both infants, however, including normal in vitro responses to phytohemagglutinin, thus postponing attempts at thymus transplantation. Both infants died suddenly at home, one at age 7 1/2 weeks and the other at age 44 weeks. At autopsy, no thymus was found in one, and a 2x2-mm thymus was detected after extensive search in the other. These cases emphasize the need for repeated monitoring of all immunologic measurements in the partial DiGeorge syndrome, so that early therapeutic intervention can be undertaken.", "contents": "Partial DiGeorge syndrome with substantial cell-mediated immunity. Results of studies on two male infants with incomplete expression of the DiGeorge syndrome are analyzed. Both infants demonstrated neonatal tetany with hypoparathyroidism, cardiovascular anomalies, and absence of a thymus shadow on roentgenographic examination. Some degree of cellular immunity was present in both infants, however, including normal in vitro responses to phytohemagglutinin, thus postponing attempts at thymus transplantation. Both infants died suddenly at home, one at age 7 1/2 weeks and the other at age 44 weeks. At autopsy, no thymus was found in one, and a 2x2-mm thymus was detected after extensive search in the other. These cases emphasize the need for repeated monitoring of all immunologic measurements in the partial DiGeorge syndrome, so that early therapeutic intervention can be undertaken."} {"id": "PMID:1258845", "title": "Colitis associated with oral clindamycin therapy. A clinical study of 16 patients.", "content": "The clinical, radiologic, and histologic features of 16 patients hospitalized with clindamycin-associated colitis are presented. The findings are tabulated and compared to 33 cases reported in the literature. The majority of patients were caucasian females over 40 years of age. The clinical presentation varied from mild persistent diarrhea to acute surgical abdomen. Proctoscopic examination revealed nonspecific colitis in 9 and pseudomembranous colitis in 7 cases. No specific radiologic or histologic fingings for postanitbiotic colitis were found. Therapy was nonspecific and varied according to the severity of the clinical course. Clinically, there appeared to be some benefit from systemic steroid therapy. 4 of the 16 patients died. None of the recovered patients have had spontaneous relapses off medication during follow-up evaluation. The pathogenic mechanism for postantibiotic colitis secondary to clindamycin remains unknown and does not appear dose related. Clindamycin therapy should be limited to disorders with specific indications.", "contents": "Colitis associated with oral clindamycin therapy. A clinical study of 16 patients. The clinical, radiologic, and histologic features of 16 patients hospitalized with clindamycin-associated colitis are presented. The findings are tabulated and compared to 33 cases reported in the literature. The majority of patients were caucasian females over 40 years of age. The clinical presentation varied from mild persistent diarrhea to acute surgical abdomen. Proctoscopic examination revealed nonspecific colitis in 9 and pseudomembranous colitis in 7 cases. No specific radiologic or histologic fingings for postanitbiotic colitis were found. Therapy was nonspecific and varied according to the severity of the clinical course. Clinically, there appeared to be some benefit from systemic steroid therapy. 4 of the 16 patients died. None of the recovered patients have had spontaneous relapses off medication during follow-up evaluation. The pathogenic mechanism for postantibiotic colitis secondary to clindamycin remains unknown and does not appear dose related. Clindamycin therapy should be limited to disorders with specific indications."} {"id": "PMID:1258846", "title": "Clindamycin-associated colitis. Review of the clinical spectrum of 47 cases.", "content": "A review of 47 cases of clindamycin-associated colitis demonstrates two groups of patients. Group I includes patients who developed diarrhea and colitis while they were still receiving clindamycin and the antibiotic was immediately stopped. Group II includes patients who developed diarrhea and colitis either after a complete course of antibiotics had been given, or while they continued to receive clindamycin. It is in this latter group of patients that significant morbidity and occasional mortality occurs.", "contents": "Clindamycin-associated colitis. Review of the clinical spectrum of 47 cases. A review of 47 cases of clindamycin-associated colitis demonstrates two groups of patients. Group I includes patients who developed diarrhea and colitis while they were still receiving clindamycin and the antibiotic was immediately stopped. Group II includes patients who developed diarrhea and colitis either after a complete course of antibiotics had been given, or while they continued to receive clindamycin. It is in this latter group of patients that significant morbidity and occasional mortality occurs."} {"id": "PMID:1258847", "title": "Relationship between the changes in gastrin levels and intestinal properties in the starved rat.", "content": "Intestinal DNA, RNA, and protein content were decreased to a greater extent than was body weight when rats were starved for 3 days. Specific lactase and maltase activity increased with progressively longer periods of starvation. Antral and serum gastrin concentration significantly decreased during the 3 days of starvation. Pentagastrin (250 mug/kg 3 times daily) was injected into a group of rats for the duration of a 3-day starvation period and caused a small but significant increase in the relative intestinal RNA and protein content and decreased lactase and maltase specific activities in comparison with the levels of 3-day starved controls. Pentagastrin thus partially reversed some of the starvation-induced changes toward fed levels. Thus, a deficiency in the trophic hormone gastrin may be partially responsible for the disproportionate changes in intestinal tissue during starvation.", "contents": "Relationship between the changes in gastrin levels and intestinal properties in the starved rat. Intestinal DNA, RNA, and protein content were decreased to a greater extent than was body weight when rats were starved for 3 days. Specific lactase and maltase activity increased with progressively longer periods of starvation. Antral and serum gastrin concentration significantly decreased during the 3 days of starvation. Pentagastrin (250 mug/kg 3 times daily) was injected into a group of rats for the duration of a 3-day starvation period and caused a small but significant increase in the relative intestinal RNA and protein content and decreased lactase and maltase specific activities in comparison with the levels of 3-day starved controls. Pentagastrin thus partially reversed some of the starvation-induced changes toward fed levels. Thus, a deficiency in the trophic hormone gastrin may be partially responsible for the disproportionate changes in intestinal tissue during starvation."} {"id": "PMID:1258848", "title": "The effect of cholecystokinin-pancreozymin on circulating gastrin levels in man and dog.", "content": "Perfusion of the jejunum with a mixture of amino acids (MAA) stimulates cholecystokinin-pancreozymin (CCK) release in man. Since gastrin is normally found in the small intestine, studies were conducted to determine if MAA perfusion had an effect on circulating serum gastrin levels in man. In man, endogenous stimulation of CCK had no effect on gastrin release; however, when CCK was given exogenously (10% pure form), serum gastrin levels were significantly increased. In dogs, the 10% pure CCK given exogenously also significantly increased gastrin concentrations, while the pure CCK octapeptide did not. Cross-reactivity between CCK and the gastrin antibody was minimal and could not be shown to be responsible for the serum gastrin elevations. Neither the physiological release of CCK in humans nor exogenous administration of CCK octapeptide in dogs at a dose equivalent to maximal stimulation of pancreatic secretion in humans significantly altered peripheral venous serum levels of immunoreactive gastrin. Therefore, we conclude that the gastrinemic response of exogenous CCK (10% pure) in man and dog is probably due to an impurity in the CCK preparation; when studying the effects of CCK on the gastrointestinal tract, only the pure CCK or the octapeptide should be used.", "contents": "The effect of cholecystokinin-pancreozymin on circulating gastrin levels in man and dog. Perfusion of the jejunum with a mixture of amino acids (MAA) stimulates cholecystokinin-pancreozymin (CCK) release in man. Since gastrin is normally found in the small intestine, studies were conducted to determine if MAA perfusion had an effect on circulating serum gastrin levels in man. In man, endogenous stimulation of CCK had no effect on gastrin release; however, when CCK was given exogenously (10% pure form), serum gastrin levels were significantly increased. In dogs, the 10% pure CCK given exogenously also significantly increased gastrin concentrations, while the pure CCK octapeptide did not. Cross-reactivity between CCK and the gastrin antibody was minimal and could not be shown to be responsible for the serum gastrin elevations. Neither the physiological release of CCK in humans nor exogenous administration of CCK octapeptide in dogs at a dose equivalent to maximal stimulation of pancreatic secretion in humans significantly altered peripheral venous serum levels of immunoreactive gastrin. Therefore, we conclude that the gastrinemic response of exogenous CCK (10% pure) in man and dog is probably due to an impurity in the CCK preparation; when studying the effects of CCK on the gastrointestinal tract, only the pure CCK or the octapeptide should be used."} {"id": "PMID:1258851", "title": "Identical twins discordant for ulcerative colitis with colon cancer.", "content": "A 22-year-old patient with a 16-year history of ulcerative colitis who developed multifocal anaplastic colon cancer is presented. His identical twin, proven by blood type, HL-A, and fingerprint analyses, has been completely asymptomatic. This report suggests that ulcerative colitis results from a polygenic predisposition without full penetrance. Subsequent development of colon cancer seems more likely related to the inflammatory disease that an independent genetic determinant.", "contents": "Identical twins discordant for ulcerative colitis with colon cancer. A 22-year-old patient with a 16-year history of ulcerative colitis who developed multifocal anaplastic colon cancer is presented. His identical twin, proven by blood type, HL-A, and fingerprint analyses, has been completely asymptomatic. This report suggests that ulcerative colitis results from a polygenic predisposition without full penetrance. Subsequent development of colon cancer seems more likely related to the inflammatory disease that an independent genetic determinant."} {"id": "PMID:1258852", "title": "Acute colitis resembling ulcerative colitis in the hemolytic-uremic syndrome.", "content": "The case report of a 10-year-old boy, admitted to the hospital after he had experienced 4 days of periumbilical abdominal pain, intermittent vomiting, and diarrhea, is presented. He had proctoscopic and radiologic findings resembling ulcerative colitis. However, further analysis of laboratory data suggested hemolytic-uremic syndrome. Since the patient in the pediatric age group presents with a clinical picture mimicking ulcerative colitis, this hemolytic-uremic syndrome should be included in the differential diagnosis. Examination of a peripheral smear revealing typical findings of microangiogpathic, hemolytic anemia, thrombocytopenia, and a rising blood urea nitrogen value will lead to the diagnosis of hemolytic-uremic syndrome and early appropriate therapy.", "contents": "Acute colitis resembling ulcerative colitis in the hemolytic-uremic syndrome. The case report of a 10-year-old boy, admitted to the hospital after he had experienced 4 days of periumbilical abdominal pain, intermittent vomiting, and diarrhea, is presented. He had proctoscopic and radiologic findings resembling ulcerative colitis. However, further analysis of laboratory data suggested hemolytic-uremic syndrome. Since the patient in the pediatric age group presents with a clinical picture mimicking ulcerative colitis, this hemolytic-uremic syndrome should be included in the differential diagnosis. Examination of a peripheral smear revealing typical findings of microangiogpathic, hemolytic anemia, thrombocytopenia, and a rising blood urea nitrogen value will lead to the diagnosis of hemolytic-uremic syndrome and early appropriate therapy."} {"id": "PMID:1258855", "title": "An outbreak of nosocomial Proteus rettgeri urinary tract infection.", "content": "Between December 1, 1971, and November 30, 1972, 11 patients on a single physical rehabilitation ward in a large St. Louis, Missouri, community hospital developed Proteus rettgeri urinary tract infections; P. rettgeri isolates from each patient were indole-negative and resistant in vitro to all antibiotics tested. Infected patients were more likely to have indwelling urinary tract catheters than were matched control patients, and all had previously received systemic antibiotic therapy. Retrospective epidemiologic investigation and microbiologic samplig at the time of the investigation failed to detect a common source of infection. Infected patients appeared to be the major reservoir of the epidemic strain, and indirect-contact transmission of the organism via nursing personnel probably occurred. Data collected from a prospective study suggested that placing catheterized patients in rooms that did not contain other catheterized patients may be an effective control measure.", "contents": "An outbreak of nosocomial Proteus rettgeri urinary tract infection. Between December 1, 1971, and November 30, 1972, 11 patients on a single physical rehabilitation ward in a large St. Louis, Missouri, community hospital developed Proteus rettgeri urinary tract infections; P. rettgeri isolates from each patient were indole-negative and resistant in vitro to all antibiotics tested. Infected patients were more likely to have indwelling urinary tract catheters than were matched control patients, and all had previously received systemic antibiotic therapy. Retrospective epidemiologic investigation and microbiologic samplig at the time of the investigation failed to detect a common source of infection. Infected patients appeared to be the major reservoir of the epidemic strain, and indirect-contact transmission of the organism via nursing personnel probably occurred. Data collected from a prospective study suggested that placing catheterized patients in rooms that did not contain other catheterized patients may be an effective control measure."} {"id": "PMID:1258856", "title": "Hospital-acquired infections. I. Surveillance in a university hospital.", "content": "A new system of surveillance is described for detecting hospital-aquired infections. Surveillance begins on the ward where a weekly review of the nursing care plan (Kardex) is used to select high risk patients (approximately 65% of the total population) for a subsequent chart review. A nurse-epidemiologist required 16-25 hr per week to perform surveillance and 4 more hr to organize line listings of infected patients. The Kardex review was 82 to 94 percent accurate in detecting nosocomial infections when compared to prospective reviews of the charts of all hospitalized patients. The new surveillance method was more accurate than a system based on weekly chart reviews of all patients receiving systemic antibiotics and/or of all patients with fever (temperature less than or equal to 37.8 C orally). In addition, it was more accurate and offered advantages over a system in which surveillance depended primarily on the bacteriology laboratory. Over a 12-month period 1154 hospital-acquired infections were identified for a 7% annual infection rate. Data from ongoing surveillance are used to record accurate infection rates by service, to define the risk of various hospital procedures, and to monitor for common source outbreaks of infection.", "contents": "Hospital-acquired infections. I. Surveillance in a university hospital. A new system of surveillance is described for detecting hospital-aquired infections. Surveillance begins on the ward where a weekly review of the nursing care plan (Kardex) is used to select high risk patients (approximately 65% of the total population) for a subsequent chart review. A nurse-epidemiologist required 16-25 hr per week to perform surveillance and 4 more hr to organize line listings of infected patients. The Kardex review was 82 to 94 percent accurate in detecting nosocomial infections when compared to prospective reviews of the charts of all hospitalized patients. The new surveillance method was more accurate than a system based on weekly chart reviews of all patients receiving systemic antibiotics and/or of all patients with fever (temperature less than or equal to 37.8 C orally). In addition, it was more accurate and offered advantages over a system in which surveillance depended primarily on the bacteriology laboratory. Over a 12-month period 1154 hospital-acquired infections were identified for a 7% annual infection rate. Data from ongoing surveillance are used to record accurate infection rates by service, to define the risk of various hospital procedures, and to monitor for common source outbreaks of infection."} {"id": "PMID:1258857", "title": "Mortality among rubber workers. I. White male union employees in Akron, Ohio.", "content": "Mortality among a cohort of 13,571 white male rubber workers in Akron, Ohio is described. Mortality from all causes was 82% of that expected on the basis of death rates for US white males. Excess deaths from cancer (observed/expected numbers) in specific sites among workers in specific work areas include stomach:processing (18/9.9); large intestine: processing (14/10.5); lung: tire curing (20/12.4): bladder: all workers (48/39.5); brain: tire building (7/3.7): lymphatic: tire building (11/7.1): and leukemia: all workers (55/43.0). In general, excess cancer deaths occurred most often among men who started working between ages 35 and 44 and prior to 1935, who worked 25-34 years and were over age 74 at death, and who died after 1954.", "contents": "Mortality among rubber workers. I. White male union employees in Akron, Ohio. Mortality among a cohort of 13,571 white male rubber workers in Akron, Ohio is described. Mortality from all causes was 82% of that expected on the basis of death rates for US white males. Excess deaths from cancer (observed/expected numbers) in specific sites among workers in specific work areas include stomach:processing (18/9.9); large intestine: processing (14/10.5); lung: tire curing (20/12.4): bladder: all workers (48/39.5); brain: tire building (7/3.7): lymphatic: tire building (11/7.1): and leukemia: all workers (55/43.0). In general, excess cancer deaths occurred most often among men who started working between ages 35 and 44 and prior to 1935, who worked 25-34 years and were over age 74 at death, and who died after 1954."} {"id": "PMID:1258858", "title": "Some atherogenic concomitants of menopause: The Framingham Study.", "content": "Longitudinal assessment of the effect of change in menopausal status on seven biologic concomitants was made in 40- to 51-year-old women from the cohort of 1686 women premenopausal at the initial Framingham examination and subsequently followed for nine biennial examinations. Within this age range, women of any specific age undergoing natural menopause were leaner at the exam prior to menopause than their controls; while women undergoing surgical menopause with bilateral oophorectomy were heavier. Hemoglobin levels rose after menopause. There was a rise in serum cholesterol levels between the premenopausal and menopausal examinations in natural menopause and in surgical menopause with bilateral oophorectomy. This rise was not seen in surgical menopause without bilateral oophorectomy. No significant changes in weight, blood pressure, blood glucose or vital capacity were found to accompany the menopause.", "contents": "Some atherogenic concomitants of menopause: The Framingham Study. Longitudinal assessment of the effect of change in menopausal status on seven biologic concomitants was made in 40- to 51-year-old women from the cohort of 1686 women premenopausal at the initial Framingham examination and subsequently followed for nine biennial examinations. Within this age range, women of any specific age undergoing natural menopause were leaner at the exam prior to menopause than their controls; while women undergoing surgical menopause with bilateral oophorectomy were heavier. Hemoglobin levels rose after menopause. There was a rise in serum cholesterol levels between the premenopausal and menopausal examinations in natural menopause and in surgical menopause with bilateral oophorectomy. This rise was not seen in surgical menopause without bilateral oophorectomy. No significant changes in weight, blood pressure, blood glucose or vital capacity were found to accompany the menopause."} {"id": "PMID:1258859", "title": "Psychosocial factors and the risk of myocardial infarctions in white women.", "content": "The relationship of risk of myocardial infarction (tmi) to psychosocial factors was studied retrospectively in 107 white women hospitalized with first MI's and in 218 controls hospitalized for other diseases. Meical records were abstracted and the women were interviewed. Psychosocial factors associated with MI were educational discrepancy, in which the patient ha less education than her husband, householo crowding and late birth order. Eoucational discrepancy was independently associated with MI, but household crowding and birth order seemed to act as risk factors for MI only when certain biological risk factors were also present. The findings indicate that certain psychosocial factors related to risk of MI in white males are also risk factors for MI in white females especially in association with biologic risk factors. Thus the effects of certain psychosocial factors may assume clinical importance only when interacting with an underlying disease state as indicated by the presence of major biologic risk factors.", "contents": "Psychosocial factors and the risk of myocardial infarctions in white women. The relationship of risk of myocardial infarction (tmi) to psychosocial factors was studied retrospectively in 107 white women hospitalized with first MI's and in 218 controls hospitalized for other diseases. Meical records were abstracted and the women were interviewed. Psychosocial factors associated with MI were educational discrepancy, in which the patient ha less education than her husband, householo crowding and late birth order. Eoucational discrepancy was independently associated with MI, but household crowding and birth order seemed to act as risk factors for MI only when certain biological risk factors were also present. The findings indicate that certain psychosocial factors related to risk of MI in white males are also risk factors for MI in white females especially in association with biologic risk factors. Thus the effects of certain psychosocial factors may assume clinical importance only when interacting with an underlying disease state as indicated by the presence of major biologic risk factors."} {"id": "PMID:1258860", "title": "Life dissatisfactions, job dissatisfaction and illness of married men over time.", "content": "This study examines the degree to which job and marital satisfaction and participation in leisure activities could predict concurrent and future health status relative to ethnicity, class and occupational factors, and mental health. Data were obtained from a longitudinal study of a random sample of 1034 Manhattan families with at least one child 6 to 18 years of age. The wives in these families were interviewed twice at 5-year intervals. Multiple regression analyses, using variables abstracted from the records of 640 wives of working husbands, indicated that husbands' health status at Time I (R = .33) and Time II, 5 years later (R = .28) was significantly predicted by the Time I assessments on 12 independent variables. The largest single unique contributor, i.e. net of all other independent variables, to concurrent husband's health was job dissatisfaction (partial r = .15), followed by husband's institutionalization for mental illness (r = .14), being Spanish (r = .10), and the factor of Unhappy Marriage (r = .09). This preliminary investigation indicated that uncertain life satisfactions were important predictors for either concurrent or future health status which operated across class, ethnic, occupational and mental health factors. These findings tend to support models which postulate stressful psychosocial conditions as potential etiologic agents in the development of illness.", "contents": "Life dissatisfactions, job dissatisfaction and illness of married men over time. This study examines the degree to which job and marital satisfaction and participation in leisure activities could predict concurrent and future health status relative to ethnicity, class and occupational factors, and mental health. Data were obtained from a longitudinal study of a random sample of 1034 Manhattan families with at least one child 6 to 18 years of age. The wives in these families were interviewed twice at 5-year intervals. Multiple regression analyses, using variables abstracted from the records of 640 wives of working husbands, indicated that husbands' health status at Time I (R = .33) and Time II, 5 years later (R = .28) was significantly predicted by the Time I assessments on 12 independent variables. The largest single unique contributor, i.e. net of all other independent variables, to concurrent husband's health was job dissatisfaction (partial r = .15), followed by husband's institutionalization for mental illness (r = .14), being Spanish (r = .10), and the factor of Unhappy Marriage (r = .09). This preliminary investigation indicated that uncertain life satisfactions were important predictors for either concurrent or future health status which operated across class, ethnic, occupational and mental health factors. These findings tend to support models which postulate stressful psychosocial conditions as potential etiologic agents in the development of illness."} {"id": "PMID:1258861", "title": "Previous fetal loss and risk of sudden infant death syndrome in subsequent offspring.", "content": "The relationships between previous fetal loss (obtained by mother's statement) and certain categories of infant death including probable instances of the sudden infant death syndrome (SIDSp) were examined. The deaths were those occurring among the cohort of live singleton births born in the State of North Carolina, 1960-1967. SIDSp were defined by age (28-364 days), place of death (outside the hospital), and certain ICD code numbers of the 7th Revision (273, 331, 422.2, 491-493, 500-501, 522, 525, 527.2, 762, 795 and 924). Other deaths in the postneonatal period were dichotomized between congenital malformations (ICD 750-759) and all other causes combined. Neonatal deaths were classified as due to either congenital malformations or other causes. For neonatal deaths and for all categories of deaths other than SIDSp in the postneonatal period there was a strong tendency for the standardized mortality ratios (SMR) to increase with increasing history of previous fetal loss. This was true for blacks and whites, and for both mothers under and over 25 years of age. The SMR for SIDSp, on the other hand, suggested an opposite association among blacks and little association among whites. Overall there was a significant difference between the patterns for SIDSp and all other postneonatal causes of death combined.", "contents": "Previous fetal loss and risk of sudden infant death syndrome in subsequent offspring. The relationships between previous fetal loss (obtained by mother's statement) and certain categories of infant death including probable instances of the sudden infant death syndrome (SIDSp) were examined. The deaths were those occurring among the cohort of live singleton births born in the State of North Carolina, 1960-1967. SIDSp were defined by age (28-364 days), place of death (outside the hospital), and certain ICD code numbers of the 7th Revision (273, 331, 422.2, 491-493, 500-501, 522, 525, 527.2, 762, 795 and 924). Other deaths in the postneonatal period were dichotomized between congenital malformations (ICD 750-759) and all other causes combined. Neonatal deaths were classified as due to either congenital malformations or other causes. For neonatal deaths and for all categories of deaths other than SIDSp in the postneonatal period there was a strong tendency for the standardized mortality ratios (SMR) to increase with increasing history of previous fetal loss. This was true for blacks and whites, and for both mothers under and over 25 years of age. The SMR for SIDSp, on the other hand, suggested an opposite association among blacks and little association among whites. Overall there was a significant difference between the patterns for SIDSp and all other postneonatal causes of death combined."} {"id": "PMID:1258862", "title": "Investigating possible effects of abestos in city water: surveillance of gastrointestinal cancer incidence in Duluth, Minnesota.", "content": "The recent discovery of over one million asbestos-like fibers per liter of Duluth tap water and the suggestive evidence of a link between certain gastrointestinal (GI) cancers and work exposure to asbestos fibers in the air prompted this study. GI cancer incidence data were gathered for Duluth in the same manner as data previously gathered for comparison cities, Minneapolis and St. Paul. Although some differences in GI cancer incidence occurred among the three cities in 1969-1971, there was no consistent pattern of statistically significant differences observed. The number of GI cancers diagnosed in Duluth residents in 1972 was similar to that in each of the previous three years. This study represents the start of ongoing cancer surveillance in Duluth.", "contents": "Investigating possible effects of abestos in city water: surveillance of gastrointestinal cancer incidence in Duluth, Minnesota. The recent discovery of over one million asbestos-like fibers per liter of Duluth tap water and the suggestive evidence of a link between certain gastrointestinal (GI) cancers and work exposure to asbestos fibers in the air prompted this study. GI cancer incidence data were gathered for Duluth in the same manner as data previously gathered for comparison cities, Minneapolis and St. Paul. Although some differences in GI cancer incidence occurred among the three cities in 1969-1971, there was no consistent pattern of statistically significant differences observed. The number of GI cancers diagnosed in Duluth residents in 1972 was similar to that in each of the previous three years. This study represents the start of ongoing cancer surveillance in Duluth."} {"id": "PMID:1258863", "title": "Population serum urate levels and their correlates. The Sherbrooke regional study.", "content": "A natural population has been studied for its serum urate levels and for host factors associated with these levels. Householdhood, ethnicity, drug and alcohol use were found to be negligible behavioral attributes with respect to population serum urate concentrations. Of interest among significant correlates of serum urate are smoking behavior, serum protein, creatinine, calcium and monocyte count. Predominant statistically significant host factors, however, are sex, body weight and age, body weight being linearly related in both sexes and age in females only.", "contents": "Population serum urate levels and their correlates. The Sherbrooke regional study. A natural population has been studied for its serum urate levels and for host factors associated with these levels. Householdhood, ethnicity, drug and alcohol use were found to be negligible behavioral attributes with respect to population serum urate concentrations. Of interest among significant correlates of serum urate are smoking behavior, serum protein, creatinine, calcium and monocyte count. Predominant statistically significant host factors, however, are sex, body weight and age, body weight being linearly related in both sexes and age in females only."} {"id": "PMID:1258864", "title": "An outbreak of type B hepatitis associated with transfusion of plasma protein fraction.", "content": "An outbreak of type B hepatitis followed transfusion with a single lot of plasma protein fraction (PPF) at a 1200-bed hospital in June and July 1973. Of 51 recipients of the product, 31 were available as a study population and 19 (61%) had an illness compatible with hepatitis. Epidemiologic and serologic investigations provided firm evidence that this material was the vehicle for transmission of disease to its recipients. Recipients of four other PPF lots from the same manufacturer were studied. Two of these lots were also associated with extremely high clinical hepatitis attack rates (45% and 55%). The other two lots, which had been prepared from donor plasma contributing to the composition of the initially-studied PPF lot, failed to produced clinical illness, although one of these lots was associated with a high prevalence of hepatitis B seropositivity in recipients. Thus, a broad spectrum of clinical and serologic responses was evident in PPF produced from similar donor plasma and pasteurized in the same bulk container. This study is the first to incriminate heat-treated PPF in transmission of type B hepatitis and suggests the need for further studies of the effect of pasteurization cycles on inactivation of hepatitis B virus.", "contents": "An outbreak of type B hepatitis associated with transfusion of plasma protein fraction. An outbreak of type B hepatitis followed transfusion with a single lot of plasma protein fraction (PPF) at a 1200-bed hospital in June and July 1973. Of 51 recipients of the product, 31 were available as a study population and 19 (61%) had an illness compatible with hepatitis. Epidemiologic and serologic investigations provided firm evidence that this material was the vehicle for transmission of disease to its recipients. Recipients of four other PPF lots from the same manufacturer were studied. Two of these lots were also associated with extremely high clinical hepatitis attack rates (45% and 55%). The other two lots, which had been prepared from donor plasma contributing to the composition of the initially-studied PPF lot, failed to produced clinical illness, although one of these lots was associated with a high prevalence of hepatitis B seropositivity in recipients. Thus, a broad spectrum of clinical and serologic responses was evident in PPF produced from similar donor plasma and pasteurized in the same bulk container. This study is the first to incriminate heat-treated PPF in transmission of type B hepatitis and suggests the need for further studies of the effect of pasteurization cycles on inactivation of hepatitis B virus."} {"id": "PMID:1258865", "title": "Rabies immunization of red foxes (Vulpes fulva) with vaccine in sausage baits.", "content": "Foxes were orally vaccinated against rabies with two modified live vaccine viruses, ERA/BHK-21 and PRI strain, in sausage baits. The baits proved acceptable to caged foxes and effectively delivered immunizing doses of vaccine. Antibody profiles on the vaccinated foxes and intramuscular challenge with \"street\" rabies virus showed the ERA/BHK-21 vaccine to be more effective than the PRI vaccine. The addition of a stabilizer helped maintain virus titers when the baits were subjected to high (35 C) temperature.", "contents": "Rabies immunization of red foxes (Vulpes fulva) with vaccine in sausage baits. Foxes were orally vaccinated against rabies with two modified live vaccine viruses, ERA/BHK-21 and PRI strain, in sausage baits. The baits proved acceptable to caged foxes and effectively delivered immunizing doses of vaccine. Antibody profiles on the vaccinated foxes and intramuscular challenge with \"street\" rabies virus showed the ERA/BHK-21 vaccine to be more effective than the PRI vaccine. The addition of a stabilizer helped maintain virus titers when the baits were subjected to high (35 C) temperature."} {"id": "PMID:1258866", "title": "Recent trends in violent deaths among young adults in the United States.", "content": "Those Americans who feel that theirs has become an increasingly violent society have support for that belief in recent mortality statistics. Since 1960, death rates in the United States among young adults from motor vehicle accidents, homicide, and suicide have increased dramatically. As of 1973, homicide and suicide rates have shown no indication of leveling off. Death rates from nonviolent causes among young adults, however, are declining, particularly among nonwhite females.", "contents": "Recent trends in violent deaths among young adults in the United States. Those Americans who feel that theirs has become an increasingly violent society have support for that belief in recent mortality statistics. Since 1960, death rates in the United States among young adults from motor vehicle accidents, homicide, and suicide have increased dramatically. As of 1973, homicide and suicide rates have shown no indication of leveling off. Death rates from nonviolent causes among young adults, however, are declining, particularly among nonwhite females."} {"id": "PMID:1258873", "title": "Looking ahead--the report of the Study Commission on Pharmacy.", "content": "The findings and recommendations of the Study Commission on Pharmacy are presented. The Commission defined pharmacy as a knowledge system which produces a service. Practitioners in specific areas of pharmacy are considered to possess both common and differentiated knowledge and skills. While pharmacy as a system is viewed as effective and efficient with reference to drug products, it is far from satisfactory with reference to drug knowledge and information. Current forces of change in the health care system and forces of change internal to pharmacy are discussed in relation to their impact on pharmacists for the future. The Commission recommended that pharmacy should move to meet the health care system's unmet needs which involve drugs and drug information. Specific recommendations are summarized regarding educational objectives, the curriculum, the faculty and credentialling. These recommendations call for heavier emphasis in pharmacy education on the behavioral and social sciences, the establishment of a small body of \"clinical scientists,\" and the creation of a National Board of Pharmacy Examiners.", "contents": "Looking ahead--the report of the Study Commission on Pharmacy. The findings and recommendations of the Study Commission on Pharmacy are presented. The Commission defined pharmacy as a knowledge system which produces a service. Practitioners in specific areas of pharmacy are considered to possess both common and differentiated knowledge and skills. While pharmacy as a system is viewed as effective and efficient with reference to drug products, it is far from satisfactory with reference to drug knowledge and information. Current forces of change in the health care system and forces of change internal to pharmacy are discussed in relation to their impact on pharmacists for the future. The Commission recommended that pharmacy should move to meet the health care system's unmet needs which involve drugs and drug information. Specific recommendations are summarized regarding educational objectives, the curriculum, the faculty and credentialling. These recommendations call for heavier emphasis in pharmacy education on the behavioral and social sciences, the establishment of a small body of \"clinical scientists,\" and the creation of a National Board of Pharmacy Examiners."} {"id": "PMID:1258874", "title": "Comparison of methods for detection of particulate matter in large-volume perenterals.", "content": "The particulate matter content of six commonly used types of large-volume parenteral solutions was evaluated using five methods. The five methods were: (1) visual examination with the naked eye under diffuse light, (2) visual examination with a 2.5 diopter lens under diffuse light, (3) examination with a light scattering apparatus, (4) instrumental examination using the Prototron particle counter, and (5) a membrane filtration and microscopic examination technique. The visual methods (1) and (2) proved to be inadequate because of the insensitivity and high degree of subjectivity. The light-scattering apparatus was reasonably accurate and a considerable improvement over the first two techniques. The Prototron instrument was shown to be capable of predicting whether a solution would pass or fail the recently adopted USP-NF standards for particulate matter content, when compared with the membrane filtration and microscopic examination technique. All of the solutions tested were found to contain very low levels of particulate matter in relation to the USP-NF standard. It is recommended that this recently adopted standard be reevaluated with a view toward increased stringency.", "contents": "Comparison of methods for detection of particulate matter in large-volume perenterals. The particulate matter content of six commonly used types of large-volume parenteral solutions was evaluated using five methods. The five methods were: (1) visual examination with the naked eye under diffuse light, (2) visual examination with a 2.5 diopter lens under diffuse light, (3) examination with a light scattering apparatus, (4) instrumental examination using the Prototron particle counter, and (5) a membrane filtration and microscopic examination technique. The visual methods (1) and (2) proved to be inadequate because of the insensitivity and high degree of subjectivity. The light-scattering apparatus was reasonably accurate and a considerable improvement over the first two techniques. The Prototron instrument was shown to be capable of predicting whether a solution would pass or fail the recently adopted USP-NF standards for particulate matter content, when compared with the membrane filtration and microscopic examination technique. All of the solutions tested were found to contain very low levels of particulate matter in relation to the USP-NF standard. It is recommended that this recently adopted standard be reevaluated with a view toward increased stringency."} {"id": "PMID:1258875", "title": "Salary survey of hospital pharmacy residency programs.", "content": "The original purpose of this survey was to obtain sufficient salary information on residency programs to assist us in evaluating our residents' annual stipend. The data reported are intended to assist other hospital pharmacists and administrators in their efforts to maintain a fair and equitable stipend for residents in hospital pharmacy.", "contents": "Salary survey of hospital pharmacy residency programs. The original purpose of this survey was to obtain sufficient salary information on residency programs to assist us in evaluating our residents' annual stipend. The data reported are intended to assist other hospital pharmacists and administrators in their efforts to maintain a fair and equitable stipend for residents in hospital pharmacy."} {"id": "PMID:1258882", "title": "National survey of selected hospital pharmacy practices.", "content": "The incidence of 10 selected hospital pharmacy programs in short-term hospitals which contained a pharmacy was surveyed. A short questionnaire was mailed to a national sample of 738 hospitals. The 10 programs surveyed were: unit dose drug distribution; pharmacy-prepared i.v. admixtures; pharmacy-controlled drug administration; radiopharmaceutical dispensing; drug usage review; use of computers in the dispensing process; 24-hour pharmacy service; participation in group purchasing; pharmacy operation of central supply; and pharmacists' authority to select the brand or supplier of drugs. In addition, the volume of drug and supply purchases was determined. A large number of pharmacies (41%) belonged to a group purchasing plan, and a high percentage (67%) reported that pharmacists had authority to select the source of supply for all drug orders unless noted otherwise by the prescriber. Less than 10% of the hospitals had both complete unit dose drug distribution and intravenous admixture programs; an additional 10% had implemented such programs partially. Only 17% of the pharmacies in large hospitals were open 24 hours a day. Computer-assisted medication dispensing was used by 13% of the large hospitals and 5% of the small hospitals. Total pharmacy purchases for all short-term hospitals in 1974 was estimated to be 1.5 billion dollars.", "contents": "National survey of selected hospital pharmacy practices. The incidence of 10 selected hospital pharmacy programs in short-term hospitals which contained a pharmacy was surveyed. A short questionnaire was mailed to a national sample of 738 hospitals. The 10 programs surveyed were: unit dose drug distribution; pharmacy-prepared i.v. admixtures; pharmacy-controlled drug administration; radiopharmaceutical dispensing; drug usage review; use of computers in the dispensing process; 24-hour pharmacy service; participation in group purchasing; pharmacy operation of central supply; and pharmacists' authority to select the brand or supplier of drugs. In addition, the volume of drug and supply purchases was determined. A large number of pharmacies (41%) belonged to a group purchasing plan, and a high percentage (67%) reported that pharmacists had authority to select the source of supply for all drug orders unless noted otherwise by the prescriber. Less than 10% of the hospitals had both complete unit dose drug distribution and intravenous admixture programs; an additional 10% had implemented such programs partially. Only 17% of the pharmacies in large hospitals were open 24 hours a day. Computer-assisted medication dispensing was used by 13% of the large hospitals and 5% of the small hospitals. Total pharmacy purchases for all short-term hospitals in 1974 was estimated to be 1.5 billion dollars."} {"id": "PMID:1258883", "title": "Psychotropic drug therapy knowledge of health care practitioners.", "content": "The psychotropic drug therapy knowledge of eight types of health care practitioners was studied. An examination, dealing with case studies of schizophrenia, depression and mania, was developed. The categories of practitioners were: (1) clinical pharmacists in psychiatric practice, (2) psychiatrists, (3) physicians (nonpsychiatrists), (4) hospital pharmacists in mental health institutions, (5) hospital pharmacists in nonmental health institutions, (6) community pharmacists, (7) nurses in mental health institutions, and (8) nurses in nonmental health institutions. The specific areas of drug knowledge tested were: diagnosis; drug selection; side effects; adverse reactions; monitoring parameters; influence of other disease states; drug-drug interactions; drug-laboratory test interactions; and clinical drug judgment. Clinical pharmacists in psychiatric practice and psychiatrists had the highest scores, and the scores of these two groups were significantly higher than those of the other groups. Nurses practicing in nonmental health institutions had the lowest scores. The results suggested that clinical pharmacists trained in psychotropic drug therapy may be competent to manage this therapy of patients in mental health institutions. Patients receiving this therapy in nonpsychiatric facilities and in ambulatory environments are being served by physicians, nurses and pharmacists whose knowledge of psychotropic drug therapy may be inadequate.", "contents": "Psychotropic drug therapy knowledge of health care practitioners. The psychotropic drug therapy knowledge of eight types of health care practitioners was studied. An examination, dealing with case studies of schizophrenia, depression and mania, was developed. The categories of practitioners were: (1) clinical pharmacists in psychiatric practice, (2) psychiatrists, (3) physicians (nonpsychiatrists), (4) hospital pharmacists in mental health institutions, (5) hospital pharmacists in nonmental health institutions, (6) community pharmacists, (7) nurses in mental health institutions, and (8) nurses in nonmental health institutions. The specific areas of drug knowledge tested were: diagnosis; drug selection; side effects; adverse reactions; monitoring parameters; influence of other disease states; drug-drug interactions; drug-laboratory test interactions; and clinical drug judgment. Clinical pharmacists in psychiatric practice and psychiatrists had the highest scores, and the scores of these two groups were significantly higher than those of the other groups. Nurses practicing in nonmental health institutions had the lowest scores. The results suggested that clinical pharmacists trained in psychotropic drug therapy may be competent to manage this therapy of patients in mental health institutions. Patients receiving this therapy in nonpsychiatric facilities and in ambulatory environments are being served by physicians, nurses and pharmacists whose knowledge of psychotropic drug therapy may be inadequate."} {"id": "PMID:1258884", "title": "Anaphylactic shock following oral penicillin--report of two cases.", "content": "Two cases of anaphylactic shock secondary to oral penicillin therapy are presented. The clinical course and treatment of the two patients are discussed. Ways in which physicians and pharmacists may reduce the incidence and severity of anaphylactic reactions to penicillin are reviewed.", "contents": "Anaphylactic shock following oral penicillin--report of two cases. Two cases of anaphylactic shock secondary to oral penicillin therapy are presented. The clinical course and treatment of the two patients are discussed. Ways in which physicians and pharmacists may reduce the incidence and severity of anaphylactic reactions to penicillin are reviewed."} {"id": "PMID:1258886", "title": "Drug treatment of hyperlipidemia.", "content": "The most frequent indication for treatment of hyperlipidemia is for prevention of arteriosclerosis, a suspected but unproved benefit. The cornerstone of treatment of primary hyperlipidemia is diet; drugs may be added to, but do not replace, diet. When a drug is used with any patient, its potential benefits and hazards must be carefully weighed for the given subject. The subjects should be carefully followed and observed for side effects. Plasma lipids should be monitored during the course of treatment. Five drugs have been approved by the U.S. Food and Drug Administration for the treatment of hyperlipidemia: cholestyramine, clofibrate, nicotinic acid, sodium dextrothyroxine and beta-sitosterol. The use, the actions and the side effects of each and of several nonapproved agents are discussed.", "contents": "Drug treatment of hyperlipidemia. The most frequent indication for treatment of hyperlipidemia is for prevention of arteriosclerosis, a suspected but unproved benefit. The cornerstone of treatment of primary hyperlipidemia is diet; drugs may be added to, but do not replace, diet. When a drug is used with any patient, its potential benefits and hazards must be carefully weighed for the given subject. The subjects should be carefully followed and observed for side effects. Plasma lipids should be monitored during the course of treatment. Five drugs have been approved by the U.S. Food and Drug Administration for the treatment of hyperlipidemia: cholestyramine, clofibrate, nicotinic acid, sodium dextrothyroxine and beta-sitosterol. The use, the actions and the side effects of each and of several nonapproved agents are discussed."} {"id": "PMID:1258888", "title": "Bacteroides fragilis resistant to the administration of clindamycin.", "content": "The susceptibility of Bacteroides fragilis to the administration of clindamycin, and the efficacy of this agent in Bacteroides infections are well documented. Clindamycin-resistant strains of B. fragilis were isolated from two patients with bacteremia at two institutions. Clinically significant resistance to clindamycin therapy has not been noted previously in B. fragilis infections.", "contents": "Bacteroides fragilis resistant to the administration of clindamycin. The susceptibility of Bacteroides fragilis to the administration of clindamycin, and the efficacy of this agent in Bacteroides infections are well documented. Clindamycin-resistant strains of B. fragilis were isolated from two patients with bacteremia at two institutions. Clinically significant resistance to clindamycin therapy has not been noted previously in B. fragilis infections."} {"id": "PMID:1258889", "title": "Arteritis of the aged (giant cell arteritis) and fever of unexplained origin.", "content": "Arteritis of the aged (giant cell arteritis) masquerades as a degenerative, infectious, neoplastic or even functional disorder in the elderly. In the absence of obliterative vascular changes, the diagnosis is often overlooked when too rigid diagnostic criteria are employed. Four elderly women presented with fever of unexplained origin as the initial manifestation of this disease. The temporal arteries were conspicuously normal in all four, and other traditional clinical clues, such as visual disturbances, headache or manifestations of polymyalgia rheumatica were likewise infrequent of entirely absent. Influenza immunization and uncomplicated rectal surgery preceded the onset of illness in two. Anemia and an increased erythrocyte sedimentation rate are important diagnostic features, particularly in the face of spontaneous clinical improvement accompanied by defervescence and disappearance of nonspecific liver dysfunction. Occult intestinal perforation complicated steroid therapy in one case. Significant and sometimes hectic fever may be a common pattern for this arteritis in its earliest stages, when palpably abnormal temporal arteries, obliterative vascular changes and other traditional diagnostic clues are more likely to be absent.", "contents": "Arteritis of the aged (giant cell arteritis) and fever of unexplained origin. Arteritis of the aged (giant cell arteritis) masquerades as a degenerative, infectious, neoplastic or even functional disorder in the elderly. In the absence of obliterative vascular changes, the diagnosis is often overlooked when too rigid diagnostic criteria are employed. Four elderly women presented with fever of unexplained origin as the initial manifestation of this disease. The temporal arteries were conspicuously normal in all four, and other traditional clinical clues, such as visual disturbances, headache or manifestations of polymyalgia rheumatica were likewise infrequent of entirely absent. Influenza immunization and uncomplicated rectal surgery preceded the onset of illness in two. Anemia and an increased erythrocyte sedimentation rate are important diagnostic features, particularly in the face of spontaneous clinical improvement accompanied by defervescence and disappearance of nonspecific liver dysfunction. Occult intestinal perforation complicated steroid therapy in one case. Significant and sometimes hectic fever may be a common pattern for this arteritis in its earliest stages, when palpably abnormal temporal arteries, obliterative vascular changes and other traditional diagnostic clues are more likely to be absent."} {"id": "PMID:1258890", "title": "Guillain-Barr\u00e9 syndrome following administration of live measles vaccine.", "content": "In a 19 month old girl and a 10 month old girl the Guillain-Barre syndrome developed within a week after they received, respectively, live measles-rubella vaccine and live measles vaccine. The older child was immune to the rubella at the time of vaccination, but both girls demonstrated a primary measles antibody response. Serum obtained during the acute and convalescent stages from the younger child was tested for antibodies against the herpes viruses (herpes simplex, Epstein-Barr virus, cytomegalovirus and varicella-zoster) and found to be negative.", "contents": "Guillain-Barr\u00e9 syndrome following administration of live measles vaccine. In a 19 month old girl and a 10 month old girl the Guillain-Barre syndrome developed within a week after they received, respectively, live measles-rubella vaccine and live measles vaccine. The older child was immune to the rubella at the time of vaccination, but both girls demonstrated a primary measles antibody response. Serum obtained during the acute and convalescent stages from the younger child was tested for antibodies against the herpes viruses (herpes simplex, Epstein-Barr virus, cytomegalovirus and varicella-zoster) and found to be negative."} {"id": "PMID:1258891", "title": "Measles virus and Guillain-Barr\u00e9 syndrome during long-term hemodialysis.", "content": "In a black man, recently receiving long-term hemodialysis, a severe, rapidly progressive polyradiculoneuritis (Guillain-Barre syndrome) developed. Routine virologic study revealed a high antimeasles virus antibody titer (1:1280 by hemagglutination-inhibition) which progressively decreased. There was no clinical evidence of measles. Discussed here is the possible relationship between the Guillain-Barre syndrome and clinically inapparent measles associated with and perhaps modified by the uremic state.", "contents": "Measles virus and Guillain-Barr\u00e9 syndrome during long-term hemodialysis. In a black man, recently receiving long-term hemodialysis, a severe, rapidly progressive polyradiculoneuritis (Guillain-Barre syndrome) developed. Routine virologic study revealed a high antimeasles virus antibody titer (1:1280 by hemagglutination-inhibition) which progressively decreased. There was no clinical evidence of measles. Discussed here is the possible relationship between the Guillain-Barre syndrome and clinically inapparent measles associated with and perhaps modified by the uremic state."} {"id": "PMID:1258892", "title": "Multiple lentigines syndrome. Case report and review of the literature.", "content": "The multiple lentigines syndrome is reviewed and a new case is presented. The major features of this syndrome are lentigines and other cutaneous abnormalities, cardiac defects, meurologic defects, cephalofacila dysmorphism, shortness of stature, skeletal anomalies, genitourinary abnormalities, and a family history consistent with an autosomal dominant mode of inheritance. The multiple lentigines syndrome manifests markedly variable expressivity; no single finding is pathognomonic and few patients have all major features. We propose specific criteria for diagnosis.", "contents": "Multiple lentigines syndrome. Case report and review of the literature. The multiple lentigines syndrome is reviewed and a new case is presented. The major features of this syndrome are lentigines and other cutaneous abnormalities, cardiac defects, meurologic defects, cephalofacila dysmorphism, shortness of stature, skeletal anomalies, genitourinary abnormalities, and a family history consistent with an autosomal dominant mode of inheritance. The multiple lentigines syndrome manifests markedly variable expressivity; no single finding is pathognomonic and few patients have all major features. We propose specific criteria for diagnosis."} {"id": "PMID:1258894", "title": "Comparison of five methods for preparing blood smears.", "content": "An extensive study was undertaken to compare five methods of blood smear preparation. Three mechanical devices for preparing blood smears were compared to the traditional coverslip and manual wedge methods. A series of five slides was prepared from each sample of blood. One hundred-cell leukocyte differential counts, red cell morphology, and platelet distribution were compared. Differential counts along the axis and margins of each slide failed to reveal any significant distribution difference by method. On the other hand, there were a significantly fewer neutrophils as well as higher lymphocyte counts on the two spinner preparations. Subsequent analysis suggested that spinner preparations create more smudge cells in smears of normal and granulocytic leukemia patients, and significantly fewer smudge cells in smears of lymphocytic leukemia patients. Both spinner methods produced significant increases in erythrocytic target cells, spherocytes, and cells with shifted pallor; and significantly fewer burr cells and ovalocytes, as compared to the reference methods. The mechanical wedge device was most similar to both reference methods. Of the two reference methods, the cumbersome coverslip preparation apparently offers no practical advantage over wedge methods.", "contents": "Comparison of five methods for preparing blood smears. An extensive study was undertaken to compare five methods of blood smear preparation. Three mechanical devices for preparing blood smears were compared to the traditional coverslip and manual wedge methods. A series of five slides was prepared from each sample of blood. One hundred-cell leukocyte differential counts, red cell morphology, and platelet distribution were compared. Differential counts along the axis and margins of each slide failed to reveal any significant distribution difference by method. On the other hand, there were a significantly fewer neutrophils as well as higher lymphocyte counts on the two spinner preparations. Subsequent analysis suggested that spinner preparations create more smudge cells in smears of normal and granulocytic leukemia patients, and significantly fewer smudge cells in smears of lymphocytic leukemia patients. Both spinner methods produced significant increases in erythrocytic target cells, spherocytes, and cells with shifted pallor; and significantly fewer burr cells and ovalocytes, as compared to the reference methods. The mechanical wedge device was most similar to both reference methods. Of the two reference methods, the cumbersome coverslip preparation apparently offers no practical advantage over wedge methods."} {"id": "PMID:1258897", "title": "The influence of diabetes and hypertension on the results of coronary revascularization.", "content": "The effects of diabetes and hypertension on the early postoperative course of patients undergoing coronary revascularization were studied by reviewing the records of 177 patients operated upon in 1972. There were 121 nondiabetic, nonhypertensive; 32 hypertensive; ten diabetic; and 14 diabetic-hypertensive patients. The incidence of postoperative low cardiac output, renal insufficiency and arrhythmia was significantly higher in the hypertensive patient. Operative mortality ranged from 0 in diabetic patients, to 0.8 per cent in nondiabetic, nonhypertensives, to 7.1 per cent in diabetic-hypertensives and 12.5 per cent in hypertensive patients, suggesting an increased risk for the hypertensive patient. The one- to two-year follow-up results documented symptomatic improvement in 90.7 per cent of patients with little adverse effect apparent from diabetes or hypertension. Pre- and postoperative coronary angiography was carried out in 103 patients between 1968 and 1973 with a mean elapsed time between operation and postoperative angiogram of 9.3 months. The progression of atherosclerosis was graded on a 0-4 basis in both grafted and ungrafted coronary arteries. While hypertension appeared to contribute to disease progression, the incidence of vein graft and internal mammary artery bypass occlusion was not significantly affected by either diabetes or hypertension. This study has shown that while hypertension contributes to increased morbidity and mortality in the early postoperative period and an increased rate of progression of atherosclerosis, neither diabetes nor hypertension appeared to influence the one- to two-year results of coronary revascularization.", "contents": "The influence of diabetes and hypertension on the results of coronary revascularization. The effects of diabetes and hypertension on the early postoperative course of patients undergoing coronary revascularization were studied by reviewing the records of 177 patients operated upon in 1972. There were 121 nondiabetic, nonhypertensive; 32 hypertensive; ten diabetic; and 14 diabetic-hypertensive patients. The incidence of postoperative low cardiac output, renal insufficiency and arrhythmia was significantly higher in the hypertensive patient. Operative mortality ranged from 0 in diabetic patients, to 0.8 per cent in nondiabetic, nonhypertensives, to 7.1 per cent in diabetic-hypertensives and 12.5 per cent in hypertensive patients, suggesting an increased risk for the hypertensive patient. The one- to two-year follow-up results documented symptomatic improvement in 90.7 per cent of patients with little adverse effect apparent from diabetes or hypertension. Pre- and postoperative coronary angiography was carried out in 103 patients between 1968 and 1973 with a mean elapsed time between operation and postoperative angiogram of 9.3 months. The progression of atherosclerosis was graded on a 0-4 basis in both grafted and ungrafted coronary arteries. While hypertension appeared to contribute to disease progression, the incidence of vein graft and internal mammary artery bypass occlusion was not significantly affected by either diabetes or hypertension. This study has shown that while hypertension contributes to increased morbidity and mortality in the early postoperative period and an increased rate of progression of atherosclerosis, neither diabetes nor hypertension appeared to influence the one- to two-year results of coronary revascularization."} {"id": "PMID:1258900", "title": "The remote prognosis of eclamptic women. Sixth periodic report.", "content": "All but three of the 270 women surviving eclampsia at the Margaret Hague Maternity Hospital in the period 1931 through 1951 were traced to 1973-74. Seventy-six have died and 13 were not re-examined. In white women having eclampsia in the first pregnancy carried to viability the remote mortality rate is not increased over that in unselected women; in white women having eclampsia as mulitparas and in all black women the remote mortality rate is from 2 to 5 times the expected numbers. Primiparous eclamptic women are not different from women matched for age, in several epidemiologic studies, in the prevalence of hypertension or in the frequency distributions of systolic and diastolic blood pressures. There is, however, a considerable increase in the prevalence of hypertension among women having had eclampsia as multiparas and that has accounted for their increased remote death rates. The prevalence of diabetes, developing many years after eclampsia is 2.5 times the expected rate in primiparous and about 4 times the expected rate among multiparous eclamptic women. Eclampsia neither is a sign of latent essential hypertension nor causes hypertension. Hypertensive pregnancies following eclampsia indicate the probabilty of later chronic hypertension, but do not cause it.", "contents": "The remote prognosis of eclamptic women. Sixth periodic report. All but three of the 270 women surviving eclampsia at the Margaret Hague Maternity Hospital in the period 1931 through 1951 were traced to 1973-74. Seventy-six have died and 13 were not re-examined. In white women having eclampsia in the first pregnancy carried to viability the remote mortality rate is not increased over that in unselected women; in white women having eclampsia as mulitparas and in all black women the remote mortality rate is from 2 to 5 times the expected numbers. Primiparous eclamptic women are not different from women matched for age, in several epidemiologic studies, in the prevalence of hypertension or in the frequency distributions of systolic and diastolic blood pressures. There is, however, a considerable increase in the prevalence of hypertension among women having had eclampsia as multiparas and that has accounted for their increased remote death rates. The prevalence of diabetes, developing many years after eclampsia is 2.5 times the expected rate in primiparous and about 4 times the expected rate among multiparous eclamptic women. Eclampsia neither is a sign of latent essential hypertension nor causes hypertension. Hypertensive pregnancies following eclampsia indicate the probabilty of later chronic hypertension, but do not cause it."} {"id": "PMID:1258898", "title": "Case report. Mini-epidemic of thyrotoxicosis occurring in physicians.", "content": "This report describes the appearance of thyrotoxicosis over the past eight years in three male physicians working in the Division of Endocrinology at The Mount Sinai Hospital. Since no other instances of hyperthyroidism developed among the hospital medical or dental attending staff, to the authors' knowledge, during the years of 1953-1973, this incidence appears to indicate an unusual occurrence. (Information regarding other possible instances of thyrotoxicosis was obtained by questioning all of the physicians in the Division of Endocrinology at The Mount Sinai Hospital, members of the Division of Endocrinology at the other major institutions in the city and, finally, inquiry of the physicians in the Department of Medicine at The Mount Sinai Hospital.)", "contents": "Case report. Mini-epidemic of thyrotoxicosis occurring in physicians. This report describes the appearance of thyrotoxicosis over the past eight years in three male physicians working in the Division of Endocrinology at The Mount Sinai Hospital. Since no other instances of hyperthyroidism developed among the hospital medical or dental attending staff, to the authors' knowledge, during the years of 1953-1973, this incidence appears to indicate an unusual occurrence. (Information regarding other possible instances of thyrotoxicosis was obtained by questioning all of the physicians in the Division of Endocrinology at The Mount Sinai Hospital, members of the Division of Endocrinology at the other major institutions in the city and, finally, inquiry of the physicians in the Department of Medicine at The Mount Sinai Hospital.)"} {"id": "PMID:1258901", "title": "Production of experimental toxemia in the pregnant rabbit.", "content": "Experimental toxemia of pregnancy was induced in 51 of 122 rabbits by constriction of the aorta below the renal arteries. The approach was extraperitoneal and dependent on the accuracy in calibrating this stricture between 0.6 and 1.0 mm. Experimental toxemia in the rabbit was characterized by hypertension, proteinuria, weight gain, and reduced weight of the fetus. Blood pressure and blood flow studies distal to the aortic constriction demonstrated a marked diminution of blood supply below the constriction. The light microscopic changes in the kidneys and in the liver were similar to those of human toxemia. The electron microscopic changes consisted of endothelial swelling and subendothelial deposits. In a separate experiment, 22 pregnant rabbits near term had an aortic constriction varying between 0.6 and 1.0 mm. This constriction lasted 4 to 12 days. Glomerular deposits of fibrinogen were demonstrated by immunofluorescence in 20 of 22 animals. The intensity of the immunofluorescence was related to the severity and duration of the aortic stricture.", "contents": "Production of experimental toxemia in the pregnant rabbit. Experimental toxemia of pregnancy was induced in 51 of 122 rabbits by constriction of the aorta below the renal arteries. The approach was extraperitoneal and dependent on the accuracy in calibrating this stricture between 0.6 and 1.0 mm. Experimental toxemia in the rabbit was characterized by hypertension, proteinuria, weight gain, and reduced weight of the fetus. Blood pressure and blood flow studies distal to the aortic constriction demonstrated a marked diminution of blood supply below the constriction. The light microscopic changes in the kidneys and in the liver were similar to those of human toxemia. The electron microscopic changes consisted of endothelial swelling and subendothelial deposits. In a separate experiment, 22 pregnant rabbits near term had an aortic constriction varying between 0.6 and 1.0 mm. This constriction lasted 4 to 12 days. Glomerular deposits of fibrinogen were demonstrated by immunofluorescence in 20 of 22 animals. The intensity of the immunofluorescence was related to the severity and duration of the aortic stricture."} {"id": "PMID:1258899", "title": "Case report. Severe hyperuricemia, hypokalemic alkalosis and tubulointersitial nephritis.", "content": "A patient with severe idiopathic hyperuricemia and hypokalemic alkalosis was followed over a one-year period. A tubulointersitial nephritis consistent with hypokalemic nephropathy was found on biopsy. However, the possibility that the hyperuricemia contributed to the hypokalemia and renal lesion cannot be excluded. Inappropriate urinary loss of potassium could be prevented by administration of spironolactone or triameterene. Six months after initiation of allopurinol therapy with reduction of serum uric acid concentrations to normal concentrations, this potassium wasting was substantially decreased.", "contents": "Case report. Severe hyperuricemia, hypokalemic alkalosis and tubulointersitial nephritis. A patient with severe idiopathic hyperuricemia and hypokalemic alkalosis was followed over a one-year period. A tubulointersitial nephritis consistent with hypokalemic nephropathy was found on biopsy. However, the possibility that the hyperuricemia contributed to the hypokalemia and renal lesion cannot be excluded. Inappropriate urinary loss of potassium could be prevented by administration of spironolactone or triameterene. Six months after initiation of allopurinol therapy with reduction of serum uric acid concentrations to normal concentrations, this potassium wasting was substantially decreased."} {"id": "PMID:1258902", "title": "Cortisol levels in maternal venous and umbilical cord arterial and venous serum at vaginal delivery.", "content": "To provide evidence that the high levels of cortisol found in mixed cord serum at spontaneous delivery are derived from the fetus rather than the mother, arterial and venous cord samples were collected separately along with simultaneous maternal venous samples at term. In the group with spontaneous labor, the difference between umbilical arterial levels of cortisol (78.6 +/- 4.1 ng. per milliliter) exceeded venous levels (61.9 +/- 4.1 ng. per milliliter) (P less than 0.0001). In the group with induced labor, the arterial level (58.4 +/- 6.9 ng. per milliliter) did not differ significantly from the venous level (50.6 +/- 5.9 ng. per milliliter) (P greater than 0.05). In four cases where spontaneous rupture of the membranes occurred prior to induction, values were similar to those of the group with spontaneous labor. The arterial levels of the group with spontaneous labor exceeded those of the group with induced labor (P less than 0.02). These differences cannot be related to duration of labor, gestational age, or maternal cortisol concentration, none of which differed between the group with electively induced and spontaneous labor. The present data provide further evidence that a rise in fetal cortisol production independent of the mother precedes and is involved in the mechanism initiating the spontaneous onset of human labor.", "contents": "Cortisol levels in maternal venous and umbilical cord arterial and venous serum at vaginal delivery. To provide evidence that the high levels of cortisol found in mixed cord serum at spontaneous delivery are derived from the fetus rather than the mother, arterial and venous cord samples were collected separately along with simultaneous maternal venous samples at term. In the group with spontaneous labor, the difference between umbilical arterial levels of cortisol (78.6 +/- 4.1 ng. per milliliter) exceeded venous levels (61.9 +/- 4.1 ng. per milliliter) (P less than 0.0001). In the group with induced labor, the arterial level (58.4 +/- 6.9 ng. per milliliter) did not differ significantly from the venous level (50.6 +/- 5.9 ng. per milliliter) (P greater than 0.05). In four cases where spontaneous rupture of the membranes occurred prior to induction, values were similar to those of the group with spontaneous labor. The arterial levels of the group with spontaneous labor exceeded those of the group with induced labor (P less than 0.02). These differences cannot be related to duration of labor, gestational age, or maternal cortisol concentration, none of which differed between the group with electively induced and spontaneous labor. The present data provide further evidence that a rise in fetal cortisol production independent of the mother precedes and is involved in the mechanism initiating the spontaneous onset of human labor."} {"id": "PMID:1258903", "title": "Association between maternal bleeding during gestation and congenital anomalies in the offspring.", "content": "The incidence of maternal bleeding complicating the pregnancies of 326 children examined at the Jerusalem Community Center for Child and Family Development is surveyed. A history of bleeding during pregnancy was more frequent in children with congenital anomalies of the central nervous system (and/or psychomotor retardation) (33 per cent) and in children with congenital anomalies of other systems (29 per cent) than in control children (12 per cent). The implications of these findings are discussed in relation to placental pathophysiology and the pathogenesis of threatened abortion.", "contents": "Association between maternal bleeding during gestation and congenital anomalies in the offspring. The incidence of maternal bleeding complicating the pregnancies of 326 children examined at the Jerusalem Community Center for Child and Family Development is surveyed. A history of bleeding during pregnancy was more frequent in children with congenital anomalies of the central nervous system (and/or psychomotor retardation) (33 per cent) and in children with congenital anomalies of other systems (29 per cent) than in control children (12 per cent). The implications of these findings are discussed in relation to placental pathophysiology and the pathogenesis of threatened abortion."} {"id": "PMID:1258904", "title": "Placental aging monitored by gray scale echography.", "content": "With gray scale ultrasonics echography, it is possible to identify changes in placental anatomy which formerly have been recognized only by examination of the placenta after delivery. By serial examinations these changes can be detected as they occur. The significance of the changes is discussed and an association between the premature appearance of aging of the placenta and a decline in placental function is noted.", "contents": "Placental aging monitored by gray scale echography. With gray scale ultrasonics echography, it is possible to identify changes in placental anatomy which formerly have been recognized only by examination of the placenta after delivery. By serial examinations these changes can be detected as they occur. The significance of the changes is discussed and an association between the premature appearance of aging of the placenta and a decline in placental function is noted."} {"id": "PMID:1258905", "title": "Purification of naturally occurring antibody to human placental lactogen by affinity chromatography.", "content": "Antibodies against human placental lactogen (HPL) were isolated from maternal postpartum sera and nonpregnant female sera by the technique of immunoadsorption (or affinity chromatography). HPL was linked to Sepharose gel by cyanogen bromide activation and the resultant chromatographic resin was used in a repetitive column procedure to absorb and fractionate naturally occurring antibodies to HPL. The antibody to HPL was concentrated after elution from the column with a chaotropic ion, and tested for immunologic acitivity. It was determined to be an IgG molecule, and only radioimmunoelectrophoresis was sensitive enough, among the several tests performed, to show specific anti-HPL activity after treatment.", "contents": "Purification of naturally occurring antibody to human placental lactogen by affinity chromatography. Antibodies against human placental lactogen (HPL) were isolated from maternal postpartum sera and nonpregnant female sera by the technique of immunoadsorption (or affinity chromatography). HPL was linked to Sepharose gel by cyanogen bromide activation and the resultant chromatographic resin was used in a repetitive column procedure to absorb and fractionate naturally occurring antibodies to HPL. The antibody to HPL was concentrated after elution from the column with a chaotropic ion, and tested for immunologic acitivity. It was determined to be an IgG molecule, and only radioimmunoelectrophoresis was sensitive enough, among the several tests performed, to show specific anti-HPL activity after treatment."} {"id": "PMID:1258906", "title": "Outpatient postconceptional fertility control with vaginally administered 15(S) 15-methyl-PGF2alpha-methyl ester.", "content": "15(S) 15-methyl-PGF2alpha-methyl ester was administered as vaginal suppositories to terminate very early gestation in 16 outpatients who were thought to be pregnant. All patients received between 2.5 and 5.0 mg. of the prostaglandin compound. Pregnancy was confirmed later in 10 of the women. In these patients vaginal bleeding started 3 to 6 hours after the start of therapy and continued for an average of 8 days. By subjective assessment, the amount of bleeding during this time was equal to or slightly heavier than that of a normal menstruation for each woman. Patients were followed for 2 to 4 weeks with serial measurements of serum progesterone and HCG. There were no failures at early pregnancy interruption. Gastrointestinal side effects rarely were encountered; no serious complications occurred and no curettage had to be performed because of heavy bleeding. The vaginal use of the methyl ester of 15(S) 15-methyl-PGF2alpha for the termination of early pregnancy seems promising as a reliable and parctical outpatient procedure.", "contents": "Outpatient postconceptional fertility control with vaginally administered 15(S) 15-methyl-PGF2alpha-methyl ester. 15(S) 15-methyl-PGF2alpha-methyl ester was administered as vaginal suppositories to terminate very early gestation in 16 outpatients who were thought to be pregnant. All patients received between 2.5 and 5.0 mg. of the prostaglandin compound. Pregnancy was confirmed later in 10 of the women. In these patients vaginal bleeding started 3 to 6 hours after the start of therapy and continued for an average of 8 days. By subjective assessment, the amount of bleeding during this time was equal to or slightly heavier than that of a normal menstruation for each woman. Patients were followed for 2 to 4 weeks with serial measurements of serum progesterone and HCG. There were no failures at early pregnancy interruption. Gastrointestinal side effects rarely were encountered; no serious complications occurred and no curettage had to be performed because of heavy bleeding. The vaginal use of the methyl ester of 15(S) 15-methyl-PGF2alpha for the termination of early pregnancy seems promising as a reliable and parctical outpatient procedure."} {"id": "PMID:1258907", "title": "Contraceptive knowledge and practice among undergraduates at a Canadian university.", "content": "A total of 509 undergraduate students aged 17 to 23 years, were tested to assess the adequacy of their knowledge of methods of birth control. A level of adequate knowledge was arbitrarily defined a priori as one standard deviation below the mean score of a random sample of second-year medical students, who were assumed to have more than adequate knowledge on the basis of prior courses in reproductive physiology and human sexuality. Of the undergraduate population sampled, 34 per cent were found to have inadequate knowledge. This population is in need of birth control information. Of nonvirgins in the sample, 20.2 per cent risk unwanted pregnancy, the majority (78.3 per cent) in spite of adequate knowledge. This suggests that lack of motivation, rather than purely lack of information, is an important factor contributing to the unwanted pregnancy rate of the college student population.", "contents": "Contraceptive knowledge and practice among undergraduates at a Canadian university. A total of 509 undergraduate students aged 17 to 23 years, were tested to assess the adequacy of their knowledge of methods of birth control. A level of adequate knowledge was arbitrarily defined a priori as one standard deviation below the mean score of a random sample of second-year medical students, who were assumed to have more than adequate knowledge on the basis of prior courses in reproductive physiology and human sexuality. Of the undergraduate population sampled, 34 per cent were found to have inadequate knowledge. This population is in need of birth control information. Of nonvirgins in the sample, 20.2 per cent risk unwanted pregnancy, the majority (78.3 per cent) in spite of adequate knowledge. This suggests that lack of motivation, rather than purely lack of information, is an important factor contributing to the unwanted pregnancy rate of the college student population."} {"id": "PMID:1258908", "title": "Carcinoma in situ of the vagina following treatment for carcinoma of the cervix: a distinctive clinical entity.", "content": "A series of 10 patients who presented with carcinoma in situ of the vagina following treatment for carcinoma of the cervix were seen in a 3 year period and their clinical and histologic features reviewed. Vaginal lesions developed 1 to 22 years after diagnosis of carcinoma of the cervix was made. In three patients the vaginal lesions progressed to invasion. In the remaining patients repeated biopsies have revealed persistent carcinoma in situ. From this series of 10 patients we conclude that the biologic behavior of vaginal carcinoma in situ following carcinoma of the cervix resembles that of carcinoma in situ of the cervix and that carcinoma of the vagina following carcinoma of the cervix should be considered a separate clinical entity distinctive from primary invasive carcinoma of the vagina.", "contents": "Carcinoma in situ of the vagina following treatment for carcinoma of the cervix: a distinctive clinical entity. A series of 10 patients who presented with carcinoma in situ of the vagina following treatment for carcinoma of the cervix were seen in a 3 year period and their clinical and histologic features reviewed. Vaginal lesions developed 1 to 22 years after diagnosis of carcinoma of the cervix was made. In three patients the vaginal lesions progressed to invasion. In the remaining patients repeated biopsies have revealed persistent carcinoma in situ. From this series of 10 patients we conclude that the biologic behavior of vaginal carcinoma in situ following carcinoma of the cervix resembles that of carcinoma in situ of the cervix and that carcinoma of the vagina following carcinoma of the cervix should be considered a separate clinical entity distinctive from primary invasive carcinoma of the vagina."} {"id": "PMID:1258911", "title": "Vascular injuries in pelvic cancer surgery.", "content": "Although pelvic cancer surgery is attended by many difficulties, vascular injuries are actually rare. New techniques of isotopic and ultrasound monitoring allow objective assessment of such patients with vascular injury. In venous problems, absolutely precise diagnosis is now possible and in both arterial and venous injury, extra-anatomic reconstructions can be done which return the vascular status of the patient to near normal.", "contents": "Vascular injuries in pelvic cancer surgery. Although pelvic cancer surgery is attended by many difficulties, vascular injuries are actually rare. New techniques of isotopic and ultrasound monitoring allow objective assessment of such patients with vascular injury. In venous problems, absolutely precise diagnosis is now possible and in both arterial and venous injury, extra-anatomic reconstructions can be done which return the vascular status of the patient to near normal."} {"id": "PMID:1258912", "title": "Contraceptive choice and prevalence of cervical dysplasia and carcinoma in situ.", "content": "Whether use of oral contraceptives is associated with subsequent development of cervical neoplasia is an important public health question. Before evaluating this issue, we must determine if choosing oral contraceptives identifies a woman who is intrinsically at high risk of developing cervical neoplasia. We have examined the demographic and reproductive characteristics as well as cervical premalignant changes manifest by 15- to 44-year-old black women who enrolled in a public family-planning clinic. When compared to IUD acceptors, oral contraceptive acceptors did not have a disproportionately large number of women with traits which predicted for high risk of developing cervical neoplasia. Oral contraceptive acceptors, compared to IUD acceptors, did not have a higher prevalence rate of carcinoma in situ. Oral contraceptive acceptors with no Pap smears prior to initial choice of contraceptive method did have a 1.4-fold higher prevalence rate of cervical dysplasia than IUD acceptors. These results suggest that the deicision to use oral contraceptives, per se, does not identify a group of women at higher risk to develop cervical carcinoma in situ. Such a decision may, however, identify a group with a small increased propensity for developing cervical dysplasia.", "contents": "Contraceptive choice and prevalence of cervical dysplasia and carcinoma in situ. Whether use of oral contraceptives is associated with subsequent development of cervical neoplasia is an important public health question. Before evaluating this issue, we must determine if choosing oral contraceptives identifies a woman who is intrinsically at high risk of developing cervical neoplasia. We have examined the demographic and reproductive characteristics as well as cervical premalignant changes manifest by 15- to 44-year-old black women who enrolled in a public family-planning clinic. When compared to IUD acceptors, oral contraceptive acceptors did not have a disproportionately large number of women with traits which predicted for high risk of developing cervical neoplasia. Oral contraceptive acceptors, compared to IUD acceptors, did not have a higher prevalence rate of carcinoma in situ. Oral contraceptive acceptors with no Pap smears prior to initial choice of contraceptive method did have a 1.4-fold higher prevalence rate of cervical dysplasia than IUD acceptors. These results suggest that the deicision to use oral contraceptives, per se, does not identify a group of women at higher risk to develop cervical carcinoma in situ. Such a decision may, however, identify a group with a small increased propensity for developing cervical dysplasia."} {"id": "PMID:1258913", "title": "The barrel-shaped cervical carcinoma.", "content": "Twelve patients had barrel-shaped cervical carcinoma among 493 new patients with primary invasive cervical carcinoma, at the Downstate Medical Center, New York from January, 1964 to December, 1972. The incidence of barrel-shaped lesions among invasive carcinoma of the cervix was 2.43%. All 12 patients were treated with external radiation to the whole pelvis followed by two radium applications. In six patients an extrafascial hysterectomy was performed 6 to 12 weeks after radiation. Six patients died and six survived (50%). Six patients survived for over 2 years after therapy with no evidence of recurrence. Of these, four are alive and well for over 5 years. All six patients died within 20 months after therapy. The barrel-shaped cervical carcinoma fared poorly (six deaths among 12 patients or 50%) when compared with the over-all Stage I and Stage II cervical carcinoma (87 deaths among 339 patients or 25.5%).", "contents": "The barrel-shaped cervical carcinoma. Twelve patients had barrel-shaped cervical carcinoma among 493 new patients with primary invasive cervical carcinoma, at the Downstate Medical Center, New York from January, 1964 to December, 1972. The incidence of barrel-shaped lesions among invasive carcinoma of the cervix was 2.43%. All 12 patients were treated with external radiation to the whole pelvis followed by two radium applications. In six patients an extrafascial hysterectomy was performed 6 to 12 weeks after radiation. Six patients died and six survived (50%). Six patients survived for over 2 years after therapy with no evidence of recurrence. Of these, four are alive and well for over 5 years. All six patients died within 20 months after therapy. The barrel-shaped cervical carcinoma fared poorly (six deaths among 12 patients or 50%) when compared with the over-all Stage I and Stage II cervical carcinoma (87 deaths among 339 patients or 25.5%)."} {"id": "PMID:1258914", "title": "Effect of estradiol-17beta on blood flow to reproductive and nonreproductive tissues in pregnant ewes.", "content": "The effect of estradiol-17beta (1 mug per kilogram) on regional blood flow and cardiac output was studied by means of radionuclide-labeled microspheres in 6 nonpregnant and 13 pregnant ewes five to seven days after operation. Estradiol caused vasodilation in myometrium, endometrium, and placental cotyledons throughout pregnancy, but these responses were significantly less than the fifteenfold increase seen in the nonpregnant uterine tissues. Significant vasodilation also occurred in the ovaries, cervix, vagina, uterine tubes, mammary gland, skin, and adrenal glands of pregnant ewes. Cardiac output increased by 14%. No significant change in uterine oxygen consumption was associated with the increase in blood flow to the pregnant uterus.", "contents": "Effect of estradiol-17beta on blood flow to reproductive and nonreproductive tissues in pregnant ewes. The effect of estradiol-17beta (1 mug per kilogram) on regional blood flow and cardiac output was studied by means of radionuclide-labeled microspheres in 6 nonpregnant and 13 pregnant ewes five to seven days after operation. Estradiol caused vasodilation in myometrium, endometrium, and placental cotyledons throughout pregnancy, but these responses were significantly less than the fifteenfold increase seen in the nonpregnant uterine tissues. Significant vasodilation also occurred in the ovaries, cervix, vagina, uterine tubes, mammary gland, skin, and adrenal glands of pregnant ewes. Cardiac output increased by 14%. No significant change in uterine oxygen consumption was associated with the increase in blood flow to the pregnant uterus."} {"id": "PMID:1258915", "title": "Cytogenetics of methadone-managed and heroin-addicted pregnant women and their newborn infants.", "content": "Chromosomal damage was assessed prenatally and at delivery from 99 addicted pregnant women (80 from a methadone maintenance program and 19 heroin addicts) and their 101 off-spring at delivery. About 10% of the 27,907 cells scored showed chromosomal abberations. Chromosome damage was random, affected all chromosomes, and was mainly of the acentric fragment type. The per cent of hypodiploidy was significantly higher than the per cent of hyperdiploidy. In the mothers, no significant differences were found with respect to dosage and duration of methadone treatment and years of heroin abuse. No significant association was found between maternal variables and infant chromosome damage. Infants with low Apgar scores (1 to 6) had cells with significantly higher levels of chromosome damage than infants with higher scores (7 to 10).", "contents": "Cytogenetics of methadone-managed and heroin-addicted pregnant women and their newborn infants. Chromosomal damage was assessed prenatally and at delivery from 99 addicted pregnant women (80 from a methadone maintenance program and 19 heroin addicts) and their 101 off-spring at delivery. About 10% of the 27,907 cells scored showed chromosomal abberations. Chromosome damage was random, affected all chromosomes, and was mainly of the acentric fragment type. The per cent of hypodiploidy was significantly higher than the per cent of hyperdiploidy. In the mothers, no significant differences were found with respect to dosage and duration of methadone treatment and years of heroin abuse. No significant association was found between maternal variables and infant chromosome damage. Infants with low Apgar scores (1 to 6) had cells with significantly higher levels of chromosome damage than infants with higher scores (7 to 10)."} {"id": "PMID:1258916", "title": "Placental morphometric and morphologic alterations in maternal undernutrition.", "content": "Placentas, mothers, and neonates belonging to different socioeconomic groups were examined for morphometric and gross morphologic changes to assess the effect of maternal undernutrition. The mean maternal caloric intakes for socioeconomic Groups I, II, and IIII + IV are 2,919, 2420, and 1,589 calories per day, respectively, and differences were significant (P less than 0.001). The mean protein intakes were respectively, 76.1, 67.3, and 52.0 Gm. per day for socioeconomic Groups I, II, and III + IV, respectively (p less than 0.001). The birth weight, placental weight, volume, surface area, and number of cotyledon showed significantly decreasing trends (P less then 0.001) with the fall in socioeconomic group and maternal dietary intakes. Placentas of socioeconomic Group I had significantly higher incidence of well-defined cotyledons and central cord attachment. In lower socioeconomic groups and small-for-dates placentas there was significantly higher incidence of hemorrhages. There were no changes in incidences of placental infarcts, calcifications, and degeneration in various socioeconomic groups.", "contents": "Placental morphometric and morphologic alterations in maternal undernutrition. Placentas, mothers, and neonates belonging to different socioeconomic groups were examined for morphometric and gross morphologic changes to assess the effect of maternal undernutrition. The mean maternal caloric intakes for socioeconomic Groups I, II, and IIII + IV are 2,919, 2420, and 1,589 calories per day, respectively, and differences were significant (P less than 0.001). The mean protein intakes were respectively, 76.1, 67.3, and 52.0 Gm. per day for socioeconomic Groups I, II, and III + IV, respectively (p less than 0.001). The birth weight, placental weight, volume, surface area, and number of cotyledon showed significantly decreasing trends (P less then 0.001) with the fall in socioeconomic group and maternal dietary intakes. Placentas of socioeconomic Group I had significantly higher incidence of well-defined cotyledons and central cord attachment. In lower socioeconomic groups and small-for-dates placentas there was significantly higher incidence of hemorrhages. There were no changes in incidences of placental infarcts, calcifications, and degeneration in various socioeconomic groups."} {"id": "PMID:1258925", "title": "Teratogenic effects of ethyl alcohol administered to pregnant mice.", "content": "Concern has recently been renewed about detrimental effects of maternal alcoholism on human prenatal development. In light of current interest in maternal alcoholism, data are presented on the effects of ethyl alcohol administration to pregnant mice. Alcohol treatment consisted of intraperitoneal injection of 0.030 ml. per gram of body weight of a 25 per cent (v/v) solution of 95 per cent ethyl alcohol in saline. Following alcohol treatment on both of gestation days 8 and 9 or days 10 and 11 the frequency of fetal death was substantially elevated compared to saline-treated controls. Alcohol treatment on one of gestation days 7, 8, 9, 10, 11, or 12 resulted in significantly increased fetal death following alcohol treatment on day 8. The incidence of congenital anomalies was significantly increased following alcohol treatment only on gestation days 8, 9, or 10. The most frequently observed abnormalities were coloboma of the iris and ectrodactyly affecting the forepaws.", "contents": "Teratogenic effects of ethyl alcohol administered to pregnant mice. Concern has recently been renewed about detrimental effects of maternal alcoholism on human prenatal development. In light of current interest in maternal alcoholism, data are presented on the effects of ethyl alcohol administration to pregnant mice. Alcohol treatment consisted of intraperitoneal injection of 0.030 ml. per gram of body weight of a 25 per cent (v/v) solution of 95 per cent ethyl alcohol in saline. Following alcohol treatment on both of gestation days 8 and 9 or days 10 and 11 the frequency of fetal death was substantially elevated compared to saline-treated controls. Alcohol treatment on one of gestation days 7, 8, 9, 10, 11, or 12 resulted in significantly increased fetal death following alcohol treatment on day 8. The incidence of congenital anomalies was significantly increased following alcohol treatment only on gestation days 8, 9, or 10. The most frequently observed abnormalities were coloboma of the iris and ectrodactyly affecting the forepaws."} {"id": "PMID:1258926", "title": "Abnormal coagulation and fibrinolysis in eclampsia. A clinical and laboratory correlation study.", "content": "This study evaluated the existence of abnormally increased coagulation and fibrinolysis in 33 severely toxemic and eclamptic women by means of a combined hemotologic profile with clinical and morphologic correlations. The dominant findings were: different degrees of thrombocytopenia, abnormal levels of blood fibrinogen, prolonged thrombin time, and positive protamine sulfate test. Altered activated partial thromboplastin time and positive ethanol gelation test were slightly less frequent, and only few cases showed prolonged prothrombin time or early lysis of euglobulins. These abnormalities seemed to be more numerous and more pronounced in the worst cases of the series and their severity seemed to be associated with the age of the patient and the presence of previous underlying disease. These variously handicapped pregnant women exhibited worse hematologic hematologic abnormalities, and provided most of the fatal cases in the series. Finally, the main findings were discussed and commented upon.", "contents": "Abnormal coagulation and fibrinolysis in eclampsia. A clinical and laboratory correlation study. This study evaluated the existence of abnormally increased coagulation and fibrinolysis in 33 severely toxemic and eclamptic women by means of a combined hemotologic profile with clinical and morphologic correlations. The dominant findings were: different degrees of thrombocytopenia, abnormal levels of blood fibrinogen, prolonged thrombin time, and positive protamine sulfate test. Altered activated partial thromboplastin time and positive ethanol gelation test were slightly less frequent, and only few cases showed prolonged prothrombin time or early lysis of euglobulins. These abnormalities seemed to be more numerous and more pronounced in the worst cases of the series and their severity seemed to be associated with the age of the patient and the presence of previous underlying disease. These variously handicapped pregnant women exhibited worse hematologic hematologic abnormalities, and provided most of the fatal cases in the series. Finally, the main findings were discussed and commented upon."} {"id": "PMID:1258927", "title": "Erythrocyte 2,3-diphosphoglycerate in normal and hypertensive gravid women and their newborn infants.", "content": "Red blood cell 2,3-diphosphoglycerate (2,3-DPG) levels were studied in 227 normal gravid women in all stages of pregnancy, active labor, and early post partum. An increase to peak levels was observed at 19 to 22 weeks followed by a gradual fall toward normal. During labor and early post partum, 2,3-DPG again rose significantly above levels observed at term. Serial 2,3-DPG values through the third trimester, labor, and postpartum period in 11 hypertensive mothers and 20 normal gravid control subjects and their newborn infants were studied. Maternal 2,3-DPG levels were significantly higher in the hypertensive mothers when compared to control mothers at similar gestational stages. However, no difference in 2,3-DPG levels was observed when newborn infants of hypertensive mothers were compared with those of normal control subjects.", "contents": "Erythrocyte 2,3-diphosphoglycerate in normal and hypertensive gravid women and their newborn infants. Red blood cell 2,3-diphosphoglycerate (2,3-DPG) levels were studied in 227 normal gravid women in all stages of pregnancy, active labor, and early post partum. An increase to peak levels was observed at 19 to 22 weeks followed by a gradual fall toward normal. During labor and early post partum, 2,3-DPG again rose significantly above levels observed at term. Serial 2,3-DPG values through the third trimester, labor, and postpartum period in 11 hypertensive mothers and 20 normal gravid control subjects and their newborn infants were studied. Maternal 2,3-DPG levels were significantly higher in the hypertensive mothers when compared to control mothers at similar gestational stages. However, no difference in 2,3-DPG levels was observed when newborn infants of hypertensive mothers were compared with those of normal control subjects."} {"id": "PMID:1258928", "title": "Strangulation of umbilical cord by amniotic band.", "content": "Congenital malformation caused by amniotic bands is an extremely rare entity. A case report of a fetal death caused by constriction of the umbilical cord by an amniotic band which joined both hands is presented.", "contents": "Strangulation of umbilical cord by amniotic band. Congenital malformation caused by amniotic bands is an extremely rare entity. A case report of a fetal death caused by constriction of the umbilical cord by an amniotic band which joined both hands is presented."} {"id": "PMID:1258929", "title": "The effect of methadone on fetal brain function.", "content": "The effect of methadone on fetal brain function in terms of the electroencephalogram (EEG) was studied in eight short-term fetal sheep experiments by single injections of 5 to 20 mg. of methadone into the fetal circulation. Plasma methadeone concentrations (determined by radioimmunoassay) greater than 0.065 mg. per cent were associated with an immediate brief decrease in carotid blood flow, a rapid decrease in frequency and amplitude in the EEG that occasionally became isoelectric but recovered, and immediate and relatively prolonged bradycardia. Similar cardiovascular observations were obtained with plasma methadone concentrations less than 0.065 mg. per cent, but the EEG changes were either minimal or not observed. These results indicate that uptake of methadone by the fetal brain is rapid and that electrical activity and heart rate are affected.", "contents": "The effect of methadone on fetal brain function. The effect of methadone on fetal brain function in terms of the electroencephalogram (EEG) was studied in eight short-term fetal sheep experiments by single injections of 5 to 20 mg. of methadone into the fetal circulation. Plasma methadeone concentrations (determined by radioimmunoassay) greater than 0.065 mg. per cent were associated with an immediate brief decrease in carotid blood flow, a rapid decrease in frequency and amplitude in the EEG that occasionally became isoelectric but recovered, and immediate and relatively prolonged bradycardia. Similar cardiovascular observations were obtained with plasma methadone concentrations less than 0.065 mg. per cent, but the EEG changes were either minimal or not observed. These results indicate that uptake of methadone by the fetal brain is rapid and that electrical activity and heart rate are affected."} {"id": "PMID:1258930", "title": "Effect of oral contraceptives on rhythmic urinary metal excretion.", "content": "Thirteen women, six of whom were using oral contraceptive agents, between the ages of 23 and 34 years, free from illness, and without a previous clinical history of menstrual abnormality, were studied with chronobiological methods for circadian (about 24 hour) patterns of metal and creatinine excretinine excretion. Circadian rhythms were detected for the excretion of lithium, potassium, iron, sodium, copper, and creatinine. Statistically significant by lower 24 hour excretion (mesors) of lithium, potassium, and iron was detected for the subjects using oral contraceptive agents. Although all women adhered to nearly identical activity-rest (synchronization) schedules, the peak times (acrophases) of the metal excretory rhythms for oral contraceptive users were phase delayed by about two hours.", "contents": "Effect of oral contraceptives on rhythmic urinary metal excretion. Thirteen women, six of whom were using oral contraceptive agents, between the ages of 23 and 34 years, free from illness, and without a previous clinical history of menstrual abnormality, were studied with chronobiological methods for circadian (about 24 hour) patterns of metal and creatinine excretinine excretion. Circadian rhythms were detected for the excretion of lithium, potassium, iron, sodium, copper, and creatinine. Statistically significant by lower 24 hour excretion (mesors) of lithium, potassium, and iron was detected for the subjects using oral contraceptive agents. Although all women adhered to nearly identical activity-rest (synchronization) schedules, the peak times (acrophases) of the metal excretory rhythms for oral contraceptive users were phase delayed by about two hours."} {"id": "PMID:1258931", "title": "An investigation of the effects of the intrauterine contraceptive device based on a longitudinal study of a self-selected sample of Barbadian women.", "content": "The results of longitudinal study of a self-selected sample of 1,790 Barbadian women who accepted the intrauterine contraceptive device (IUD) as their method of contraception are reported. The accumulated experience of 44,000 woman months of IUD use is presented. The demographic, medical, and obstetric data on admission for 2,797 IUD acceptors and 4,296 nonacceptors are contrasted. The reproductive experience of the two groups prior to the insertion of an IUD with respect to live births, stillbirths, and miscarriages is similar while the incidence of ectopic pregnancy is shown to be different. The association between the IUD and the incidence of tubal pregnancy is evaluated, and the literature dealing with this topic is reviewed. Estimates of the relative risk of an ectopic pregnancy in a woman with an IUD in utero are given.", "contents": "An investigation of the effects of the intrauterine contraceptive device based on a longitudinal study of a self-selected sample of Barbadian women. The results of longitudinal study of a self-selected sample of 1,790 Barbadian women who accepted the intrauterine contraceptive device (IUD) as their method of contraception are reported. The accumulated experience of 44,000 woman months of IUD use is presented. The demographic, medical, and obstetric data on admission for 2,797 IUD acceptors and 4,296 nonacceptors are contrasted. The reproductive experience of the two groups prior to the insertion of an IUD with respect to live births, stillbirths, and miscarriages is similar while the incidence of ectopic pregnancy is shown to be different. The association between the IUD and the incidence of tubal pregnancy is evaluated, and the literature dealing with this topic is reviewed. Estimates of the relative risk of an ectopic pregnancy in a woman with an IUD in utero are given."} {"id": "PMID:1258932", "title": "Experience in mass Papanicolaou screening and cytologic observations of teen-age girls.", "content": "This report is based on a seven-year retrospective analysis of computerized data available from the Chicago Board of Health's Cancer Control Section and its Cytology Laboratory. All patients included were medically indigent. The cytologic specimens were obtained by the VCE technique; all Papanicolaou smears were classified with both the numerical and descriptive systems for abnormal cytology. The study cohort was composed of 33,641 teen-age patients through age 19; 58 (1.7/1,000) had abnormal cytology (Class III, IV, or V). In Chicago, from 1962 through 1969, approximately 25 per cent of the total patient load were teen-agers under the age of 19 with an extremely low yield of suspect cytology: Class III = 1.6 per month; Class IV = 0.1 per month; Class V = 0.0 per month. The Chicago Board of Health has reduced the number of Papanicolaou smears taken on young women under the age of 19; however, this conceptual approach does not exclude women under age 19 who epidemiologically and/or clinically warrant the implementation of a Papanicolaou smear with the use of Friedell's \"biologic age of the cervix\" formula.", "contents": "Experience in mass Papanicolaou screening and cytologic observations of teen-age girls. This report is based on a seven-year retrospective analysis of computerized data available from the Chicago Board of Health's Cancer Control Section and its Cytology Laboratory. All patients included were medically indigent. The cytologic specimens were obtained by the VCE technique; all Papanicolaou smears were classified with both the numerical and descriptive systems for abnormal cytology. The study cohort was composed of 33,641 teen-age patients through age 19; 58 (1.7/1,000) had abnormal cytology (Class III, IV, or V). In Chicago, from 1962 through 1969, approximately 25 per cent of the total patient load were teen-agers under the age of 19 with an extremely low yield of suspect cytology: Class III = 1.6 per month; Class IV = 0.1 per month; Class V = 0.0 per month. The Chicago Board of Health has reduced the number of Papanicolaou smears taken on young women under the age of 19; however, this conceptual approach does not exclude women under age 19 who epidemiologically and/or clinically warrant the implementation of a Papanicolaou smear with the use of Friedell's \"biologic age of the cervix\" formula."} {"id": "PMID:1258933", "title": "Association of estrone with the development of endometrial carcinoma.", "content": "Although few clinicians suspect estrogen as the prime cause of endometrial carcinoma, a retrospective study showed the following among postmenopausal women: 70 per cent of those with endometrial carcinoma and only 23 per cent of matched control subjects used estrogen systemically. Endometrial cancer developed an average of five years earlier in those taking than in those not receiving estrogen. Forty-two per cent of those with endometrial cancer had received estrogen three years or more. Most significantly, conjugated estrogens were used by 89 per cent of postmenopausal cancer patients who had received any estrogenic substance. The increased risk of endometrial cancer for all patients receiving conjugated estrogen (the risk ratio) was 7.4. This risk ratio increased with duration of conjugated estrogen exposure, from 4.6 in patients with less than three years' exposure to 9.2 in patients with three or more years' exposure.", "contents": "Association of estrone with the development of endometrial carcinoma. Although few clinicians suspect estrogen as the prime cause of endometrial carcinoma, a retrospective study showed the following among postmenopausal women: 70 per cent of those with endometrial carcinoma and only 23 per cent of matched control subjects used estrogen systemically. Endometrial cancer developed an average of five years earlier in those taking than in those not receiving estrogen. Forty-two per cent of those with endometrial cancer had received estrogen three years or more. Most significantly, conjugated estrogens were used by 89 per cent of postmenopausal cancer patients who had received any estrogenic substance. The increased risk of endometrial cancer for all patients receiving conjugated estrogen (the risk ratio) was 7.4. This risk ratio increased with duration of conjugated estrogen exposure, from 4.6 in patients with less than three years' exposure to 9.2 in patients with three or more years' exposure."} {"id": "PMID:1258934", "title": "Carbon dioxide hysteroscopy.", "content": "Hysteroscopy was performed on 75 patients undergoing a dilatation and curettage for routine gynecologic problems. For the distetnion of the uterine cavity carbon dioxide was used and found to be an adequate medium to establish a pneumometra. It provided good visualization and was simple and safe to use for the hysteroscopic examination. Arterial blood-gas determinations revealed no change in the POI PCO2, and pH with carbon dioxide insufflation. There were no complications in this series. The advantages and applications of carbon dioxide hysteroscopy are outlined.", "contents": "Carbon dioxide hysteroscopy. Hysteroscopy was performed on 75 patients undergoing a dilatation and curettage for routine gynecologic problems. For the distetnion of the uterine cavity carbon dioxide was used and found to be an adequate medium to establish a pneumometra. It provided good visualization and was simple and safe to use for the hysteroscopic examination. Arterial blood-gas determinations revealed no change in the POI PCO2, and pH with carbon dioxide insufflation. There were no complications in this series. The advantages and applications of carbon dioxide hysteroscopy are outlined."} {"id": "PMID:1258935", "title": "Dysplasia and carcinoma in situ of the uterine cervix: prevalence in very young women (under age 22). A one-year study in a health plan population.", "content": "An increased number of cervical epithelial abnormalities has been observed in women up to and including 21 years of age. The prevalence and incidence of dysplasia in adolescents and young women is increasing at a time when the incidence of cervical carcinoma is decreasing. We studied 247 women under age 22 with \"other than negative\" cytologic diagnoses identified during a one-year period (1973) in which approximately 27,500 women in this age group were screened. The prevalence rates of \"other than negative\" cytology and \"other than negative\" cytology with confirmed histopathologic abnormalities were 9/1,000 and 2.7/1,000, respectively. Repeat smears and/or tissue speciments were obtained in over 70 per cent of these cases. The majority of abnormalities identified were mild or moderate dysplasia; however eight severe dysplasias and three carcinomas in situ were identified. Fifty-nine percent of these women had a history of one or more pregnancies. Our findings emphasize the presence of dysplasia and carcinoma in situ in young women and suggest the need for re-evaluation of the age at which initiation of the Papanicolaou smear should be considered.", "contents": "Dysplasia and carcinoma in situ of the uterine cervix: prevalence in very young women (under age 22). A one-year study in a health plan population. An increased number of cervical epithelial abnormalities has been observed in women up to and including 21 years of age. The prevalence and incidence of dysplasia in adolescents and young women is increasing at a time when the incidence of cervical carcinoma is decreasing. We studied 247 women under age 22 with \"other than negative\" cytologic diagnoses identified during a one-year period (1973) in which approximately 27,500 women in this age group were screened. The prevalence rates of \"other than negative\" cytology and \"other than negative\" cytology with confirmed histopathologic abnormalities were 9/1,000 and 2.7/1,000, respectively. Repeat smears and/or tissue speciments were obtained in over 70 per cent of these cases. The majority of abnormalities identified were mild or moderate dysplasia; however eight severe dysplasias and three carcinomas in situ were identified. Fifty-nine percent of these women had a history of one or more pregnancies. Our findings emphasize the presence of dysplasia and carcinoma in situ in young women and suggest the need for re-evaluation of the age at which initiation of the Papanicolaou smear should be considered."} {"id": "PMID:1258936", "title": "Ureterovaginal fistula as a complication of radical pelvic surgery.", "content": "The main objection to radical hysterectomy and pelvic node dissection as a method of primary treatment for cervical carcinoma is the inherent danger to the ureters that may result in ureterovaginal fistula formation. The purpose of this paper is twofold: (1) to show that with adoption of certain surgical and clinical measures our incidence of fistula formation has been significantly reduced, and (2) to discuss the management of ureterovaginal fistula when it occurs.", "contents": "Ureterovaginal fistula as a complication of radical pelvic surgery. The main objection to radical hysterectomy and pelvic node dissection as a method of primary treatment for cervical carcinoma is the inherent danger to the ureters that may result in ureterovaginal fistula formation. The purpose of this paper is twofold: (1) to show that with adoption of certain surgical and clinical measures our incidence of fistula formation has been significantly reduced, and (2) to discuss the management of ureterovaginal fistula when it occurs."} {"id": "PMID:1258937", "title": "Slowing of active labor associated with internal fetal monitoring.", "content": "Active labor progress is generally believed to be linear. By using an ultrasonic cervimeter, which continuously records dilatation of the uterine cervix, acute decreases in active-phase dilatation followed by less rapid recoveries are found to be associated with intravaginal obstetric manipulations. These findings support the concepts that active labor may be nonlinear and regression in cervical dilatation is a real phenomenon.", "contents": "Slowing of active labor associated with internal fetal monitoring. Active labor progress is generally believed to be linear. By using an ultrasonic cervimeter, which continuously records dilatation of the uterine cervix, acute decreases in active-phase dilatation followed by less rapid recoveries are found to be associated with intravaginal obstetric manipulations. These findings support the concepts that active labor may be nonlinear and regression in cervical dilatation is a real phenomenon."} {"id": "PMID:1258938", "title": "Ovarian hemorrhage complicating warfarin sodium anticoagulant therapy.", "content": "Three cases of women in the reproductive age group who received warfarin sodium therapy for pulmonary embolism are presented. The therapy was complicated by rupture of ovarian cysts with intraperitoneal hemorrhage necessitating exploratory laparatomy. The possibility of intraperitoneal hemorrhage must be considered in patients who present with abdominal pain and a history of anticoagulant therapy. Lack of awareness of the complication may result in delay in making a correct diagnosis and instituting appropriate therapy.", "contents": "Ovarian hemorrhage complicating warfarin sodium anticoagulant therapy. Three cases of women in the reproductive age group who received warfarin sodium therapy for pulmonary embolism are presented. The therapy was complicated by rupture of ovarian cysts with intraperitoneal hemorrhage necessitating exploratory laparatomy. The possibility of intraperitoneal hemorrhage must be considered in patients who present with abdominal pain and a history of anticoagulant therapy. Lack of awareness of the complication may result in delay in making a correct diagnosis and instituting appropriate therapy."} {"id": "PMID:1258939", "title": "Puerperal infection in the antibiotic era.", "content": "Developments in etiology and treatment of puerperal infection in the last 20 years are reviewed. Emphasis is placed upon predisposing factors, microbiology and antibiotics, unusual sources of severe infection, special complications, and prophylactic antibiotics.", "contents": "Puerperal infection in the antibiotic era. Developments in etiology and treatment of puerperal infection in the last 20 years are reviewed. Emphasis is placed upon predisposing factors, microbiology and antibiotics, unusual sources of severe infection, special complications, and prophylactic antibiotics."} {"id": "PMID:1258941", "title": "Immunotherapy and chemotherapy of gynecologic cancers.", "content": "Recurrent cervical, ovarian, and breast cancers have been treated with immunochemotherapy. Optimum chemotherapeutic agents have been determined by direct and indirect methods of sensitivity determination. The Hellstr\u00f6m assay has been used for lymphocyte-tumor recognition and for cytotoxicity assays. Vaccines developed in this laboratory, consisting of autologous and allogeneic tumor-associated antigens, combined with BCG, have been used in immunotherapy. Objective tumor regression and notable clinical improvements have been observed. Forty-five advanced cases, including recurrent cancers of the cervix and ovary, along with sarcomas, breast malignancies, and melanomas, have been treated: 16 patients have died of their disease and 29 patients have survived for 6 months to 1 1/2 years. Some of these have shown either regression, total disappearance, or stabilization of their disease process. While the results of these preliminary studies are encouraging, the as yet unknown potential of this modality cannot be expected until it is applied earlier, at a time when residual tumor cells are minimal.", "contents": "Immunotherapy and chemotherapy of gynecologic cancers. Recurrent cervical, ovarian, and breast cancers have been treated with immunochemotherapy. Optimum chemotherapeutic agents have been determined by direct and indirect methods of sensitivity determination. The Hellstr\u00f6m assay has been used for lymphocyte-tumor recognition and for cytotoxicity assays. Vaccines developed in this laboratory, consisting of autologous and allogeneic tumor-associated antigens, combined with BCG, have been used in immunotherapy. Objective tumor regression and notable clinical improvements have been observed. Forty-five advanced cases, including recurrent cancers of the cervix and ovary, along with sarcomas, breast malignancies, and melanomas, have been treated: 16 patients have died of their disease and 29 patients have survived for 6 months to 1 1/2 years. Some of these have shown either regression, total disappearance, or stabilization of their disease process. While the results of these preliminary studies are encouraging, the as yet unknown potential of this modality cannot be expected until it is applied earlier, at a time when residual tumor cells are minimal."} {"id": "PMID:1258942", "title": "Fetal membrane dynamics.", "content": "The validity of the concepts of exchange and net flow and of the method used to measure them was proved by utilizing a standard artificial membrane. The exchange rates across the amniochorion of D- and L-isomers of various amino acids have been measured. They do not differ. Rates of exchange of water, glucose, and mannitol across the umbilical cord were determined and were noted to be considerably slower than the rates for these substances across the amniochorion.", "contents": "Fetal membrane dynamics. The validity of the concepts of exchange and net flow and of the method used to measure them was proved by utilizing a standard artificial membrane. The exchange rates across the amniochorion of D- and L-isomers of various amino acids have been measured. They do not differ. Rates of exchange of water, glucose, and mannitol across the umbilical cord were determined and were noted to be considerably slower than the rates for these substances across the amniochorion."} {"id": "PMID:1258943", "title": "Rate of transport of radioactive ovum models through the oviducts of individual rabbits.", "content": "The transport of radioactive ovum models of 100, 200, 400, 800, and 1,000 mu diameter through the oviducts was measured. Four surrogates of a given size were transferred into each oviduct 6 hours after injection of human chorionic gonadotropin (HCG). The surrogates were located in the oviducts 24, 48, 60, 66, and 72 hours after HCG injection with a collimated end-window Geiger-Mueller tube. Thus the time-course of the transport of each surrogate, from ampulla to uterus in the same animal, was plotted. The time-course of surrogate transport was directly related to surrogate size. Our data suggest that normal tubal patency and ovum transport function can be tested by introducing radioactive ovum surrogates of appropriate size into the oviducts and monitoring their time of arrival at the uterus.", "contents": "Rate of transport of radioactive ovum models through the oviducts of individual rabbits. The transport of radioactive ovum models of 100, 200, 400, 800, and 1,000 mu diameter through the oviducts was measured. Four surrogates of a given size were transferred into each oviduct 6 hours after injection of human chorionic gonadotropin (HCG). The surrogates were located in the oviducts 24, 48, 60, 66, and 72 hours after HCG injection with a collimated end-window Geiger-Mueller tube. Thus the time-course of the transport of each surrogate, from ampulla to uterus in the same animal, was plotted. The time-course of surrogate transport was directly related to surrogate size. Our data suggest that normal tubal patency and ovum transport function can be tested by introducing radioactive ovum surrogates of appropriate size into the oviducts and monitoring their time of arrival at the uterus."} {"id": "PMID:1258944", "title": "The significance of urinary free cortisol and progesterone in normal and anencephalic pregnancy.", "content": "Urinary free cortisol and progesterone were determined by radioimmunoassay in 18 normal and 16 anencephalic pregnancies and urinary free cortisol levels in 9 nonpregnant women. In normal pregnancy the urinary free cortisol (46.89 +/- 34.02 mug per 24 hours) was significantly higher (P less than 0.001) than that found with anencephaly (17.19 +/- 13.20 mug per 24 hours) and 2 1/2 times (P less than 0.001) the nonpregnant value (18.47 +/- 5.44 mug per 24 hours). In 12 of the anencephalic pregnancies, urinary free cortisol levels (11.05 +/- 5.56 mug per 24 hours) were significantly lower than in nonpregnant women (P less than 0.001). Urinary progesterone levels in normal pregnancy (15.57 +/- 9.66 mug per 24 hours) and anencephaly (18.54 +/- 12.69 mug per 24 hours) were comparable. The cortisol excretion values associated with anencephaly indicate that the normal fetus contributes substantially to the maternal plasma cortisol pool. Urinary free cortisol determinations may be a useful index of fetal adrenal dysfunction.", "contents": "The significance of urinary free cortisol and progesterone in normal and anencephalic pregnancy. Urinary free cortisol and progesterone were determined by radioimmunoassay in 18 normal and 16 anencephalic pregnancies and urinary free cortisol levels in 9 nonpregnant women. In normal pregnancy the urinary free cortisol (46.89 +/- 34.02 mug per 24 hours) was significantly higher (P less than 0.001) than that found with anencephaly (17.19 +/- 13.20 mug per 24 hours) and 2 1/2 times (P less than 0.001) the nonpregnant value (18.47 +/- 5.44 mug per 24 hours). In 12 of the anencephalic pregnancies, urinary free cortisol levels (11.05 +/- 5.56 mug per 24 hours) were significantly lower than in nonpregnant women (P less than 0.001). Urinary progesterone levels in normal pregnancy (15.57 +/- 9.66 mug per 24 hours) and anencephaly (18.54 +/- 12.69 mug per 24 hours) were comparable. The cortisol excretion values associated with anencephaly indicate that the normal fetus contributes substantially to the maternal plasma cortisol pool. Urinary free cortisol determinations may be a useful index of fetal adrenal dysfunction."} {"id": "PMID:1258945", "title": "Coagulation changes in eclampsia: their frequency and pathogenesis.", "content": "The maternal coagulation mechanism has been investigated in an effort to identify its role, if any, in the pathogenesis of eclampsia. Thrombocytopenia was identified in 28 of 95 cases (29 per cent), a prolonged thrombin time in 19 of 38 (50 per cent), abnormally elevated serum fibrinogen-fibrin degradation products in two of 65 (3 per cent), and circulating fibrin monomer in one out of 20 (5 per cent). Overt hemolysis was rare (2 per cent). Thus the pattern as well as the degree of change in the maternal coagulation mechanism differed remarkably from that typical of severe abruptio placentae and of prolonged retention of a dead fetus, the classic obstetric models of fast and slow disseminated intravascular coagulation. It is concluded that the coagulation changes when present in eclampsia are effect rather than cause. Moreover, the changes may evolve primarily from platelet adherence at sites of vascular endothelial damage as the consequence of segmental vasospasm and vasodilatation rather than be triggered by the escape of thromboplastin from the placenta into the maternal circulation.", "contents": "Coagulation changes in eclampsia: their frequency and pathogenesis. The maternal coagulation mechanism has been investigated in an effort to identify its role, if any, in the pathogenesis of eclampsia. Thrombocytopenia was identified in 28 of 95 cases (29 per cent), a prolonged thrombin time in 19 of 38 (50 per cent), abnormally elevated serum fibrinogen-fibrin degradation products in two of 65 (3 per cent), and circulating fibrin monomer in one out of 20 (5 per cent). Overt hemolysis was rare (2 per cent). Thus the pattern as well as the degree of change in the maternal coagulation mechanism differed remarkably from that typical of severe abruptio placentae and of prolonged retention of a dead fetus, the classic obstetric models of fast and slow disseminated intravascular coagulation. It is concluded that the coagulation changes when present in eclampsia are effect rather than cause. Moreover, the changes may evolve primarily from platelet adherence at sites of vascular endothelial damage as the consequence of segmental vasospasm and vasodilatation rather than be triggered by the escape of thromboplastin from the placenta into the maternal circulation."} {"id": "PMID:1258946", "title": "Effects of local anesthetic agents on the uterine vasculatures and myometrium.", "content": "Intravascular procaine, lidocaine, mepivacaine, and bupivacaine decrease blood flow to the placental and nonplacental vascular beds of gravid ewes by stimulating vasoconstriction and myometrial contractility. These effects appear to be direct ones since they are not affected by alpha-adrenergic blockade. Dose-response curves determined in nonpregnant ewes indicate that significant decreases in blood flow may occur at arterial blood concentrations encountered clinically. It is proposed that reduced placental blood flow is the cause of fetal bradycardia following paracervical block anesthesia. The implications of these findings in obstetric anesthesia are discussed.", "contents": "Effects of local anesthetic agents on the uterine vasculatures and myometrium. Intravascular procaine, lidocaine, mepivacaine, and bupivacaine decrease blood flow to the placental and nonplacental vascular beds of gravid ewes by stimulating vasoconstriction and myometrial contractility. These effects appear to be direct ones since they are not affected by alpha-adrenergic blockade. Dose-response curves determined in nonpregnant ewes indicate that significant decreases in blood flow may occur at arterial blood concentrations encountered clinically. It is proposed that reduced placental blood flow is the cause of fetal bradycardia following paracervical block anesthesia. The implications of these findings in obstetric anesthesia are discussed."} {"id": "PMID:1258947", "title": "Elective cesarean hysterectomy: a 5 year comparison with cesarean section.", "content": "Elective cesarean sections performed on the obstetric service at the University of Arkansas Medical Center were reviewed for the period January 1, 1970, through December 31, 1974. The purpose of the review was to compare operative and postoperative complications of cesarean section, cesarean section and tubal ligation, and cesarean section and elective hysterectomy. A total of 1,255 cesarean sections were performed of which 207 (17 per cent) were associated with tubal ligation and 242 (18 per cent) with hysterectomy. Elective cesarean hysterectomies were performed for elective sterilization (68 per cent), for medically indicated sterilizations (11 per cent), or for definitive treatment of uterine pathology(21 per cent). All cesarean sections were obstetrically indicated with the exception of 34 primary cesarean hysterectomies performed as definitive treatment of carcinoma in situ of the cervix. The operative procedures were compared in regard to the following characteristics or complications: operating time; incidence of blood transfusions, urinary tract injuries, postoperative bleeding, febrile morbidity, and other postoperative complications; and postoperative hospital days.", "contents": "Elective cesarean hysterectomy: a 5 year comparison with cesarean section. Elective cesarean sections performed on the obstetric service at the University of Arkansas Medical Center were reviewed for the period January 1, 1970, through December 31, 1974. The purpose of the review was to compare operative and postoperative complications of cesarean section, cesarean section and tubal ligation, and cesarean section and elective hysterectomy. A total of 1,255 cesarean sections were performed of which 207 (17 per cent) were associated with tubal ligation and 242 (18 per cent) with hysterectomy. Elective cesarean hysterectomies were performed for elective sterilization (68 per cent), for medically indicated sterilizations (11 per cent), or for definitive treatment of uterine pathology(21 per cent). All cesarean sections were obstetrically indicated with the exception of 34 primary cesarean hysterectomies performed as definitive treatment of carcinoma in situ of the cervix. The operative procedures were compared in regard to the following characteristics or complications: operating time; incidence of blood transfusions, urinary tract injuries, postoperative bleeding, febrile morbidity, and other postoperative complications; and postoperative hospital days."} {"id": "PMID:1258948", "title": "Cell kinetics and programmed chemotherapy for gynecologic cancer. I. Squamous-cell carcinoma.", "content": "The results of current investigation into cellular kinetics of both normal and abnormal human genital tissue have stimulated interest in programming chemotherapeutic drug regimens for the treatment of genital cancer. This report outlines the results of cell kinetic studies of normal and abnormal squamous epithelium of the female genital tract and presents preliminary results of a regimen utilizing methotrexate, hydroxyurea, and vincristine in patients with far-advanced squamous-cell cancer of the vulva, vagina, and cervix. A total of 92 patients have received 444 courses of programmed chemotherapy by either pelvic intra-arterial infusion or systemic administration of the drugs. Our results are presented and the theoretical basis of the research is discussed.", "contents": "Cell kinetics and programmed chemotherapy for gynecologic cancer. I. Squamous-cell carcinoma. The results of current investigation into cellular kinetics of both normal and abnormal human genital tissue have stimulated interest in programming chemotherapeutic drug regimens for the treatment of genital cancer. This report outlines the results of cell kinetic studies of normal and abnormal squamous epithelium of the female genital tract and presents preliminary results of a regimen utilizing methotrexate, hydroxyurea, and vincristine in patients with far-advanced squamous-cell cancer of the vulva, vagina, and cervix. A total of 92 patients have received 444 courses of programmed chemotherapy by either pelvic intra-arterial infusion or systemic administration of the drugs. Our results are presented and the theoretical basis of the research is discussed."} {"id": "PMID:1258949", "title": "Cytology and colposcopy in the diagnosis and management of preclinical carcinoma of the cervix uteri: a learning experience.", "content": "This report presents a learning experience in the use of colposcopy in the management of 254 patients consecutively and personally studied in whom one or more Papanicolaou smears suggested a cervical intraepithelial neoplasia or early invasive carcinoma. The accuracy of cytology in predicting the degree of cervical intraepithelial neoplasia and early invasive carcinoma, within the limits of confidence of the laboratory, was 84.5 per cent. The accuracy of the colposcopic impression, within the limits of confidence, was 83.5 per cent. When only those lesions that could be satisfactorily examined were considered, the accuracy of the colposcopic interpretation within the limits of confidence was found to be 96.4 per cent. Neoplastic lesions limited to the ectocervix, and lesions that extended from the ectocervix into the lower portion of the endocervical canal and lesions limited to the canal were significantly related to the age of the patient. Of the total group of 254 patients examined, 45 patients (17.7 per cent) were subjected to a diagnostic cone biopsy.", "contents": "Cytology and colposcopy in the diagnosis and management of preclinical carcinoma of the cervix uteri: a learning experience. This report presents a learning experience in the use of colposcopy in the management of 254 patients consecutively and personally studied in whom one or more Papanicolaou smears suggested a cervical intraepithelial neoplasia or early invasive carcinoma. The accuracy of cytology in predicting the degree of cervical intraepithelial neoplasia and early invasive carcinoma, within the limits of confidence of the laboratory, was 84.5 per cent. The accuracy of the colposcopic impression, within the limits of confidence, was 83.5 per cent. When only those lesions that could be satisfactorily examined were considered, the accuracy of the colposcopic interpretation within the limits of confidence was found to be 96.4 per cent. Neoplastic lesions limited to the ectocervix, and lesions that extended from the ectocervix into the lower portion of the endocervical canal and lesions limited to the canal were significantly related to the age of the patient. Of the total group of 254 patients examined, 45 patients (17.7 per cent) were subjected to a diagnostic cone biopsy."} {"id": "PMID:1258950", "title": "One hundred consecutive pars plana vitrectomies using the vitrophage.", "content": "One hundred consecutive eyes underwent vitrectomy with the disposable vitrophage via a pars plana approach. Eyes were divided into two main categories based on opacity location-in the anterior or posterior segment. Patients with posterior segment opacities had diabetic retinopathy, nondiabetic vitreous hemorrhages, retinal detachments associated with vitreous hemorrhage, bands, or membranes, and intraocular foreign bodies or silicone oil. Patients with anterior segment opacities were treated for pupillary membranes resulting from surgical trauma or perforating injuries, and for complications following cataract extraction, such as capsule breakage and vitreous loss. Postoperatively, visual acuity improved in 68% of eyes with posterior segment opacities and in 85% of eyes with anterior segment opacities. Overall, visual acuity was 20/300 or better in 45% of eyes. There were only two intraoperative retinal tears and one postoperative rhegmatogenous retinal detachment.", "contents": "One hundred consecutive pars plana vitrectomies using the vitrophage. One hundred consecutive eyes underwent vitrectomy with the disposable vitrophage via a pars plana approach. Eyes were divided into two main categories based on opacity location-in the anterior or posterior segment. Patients with posterior segment opacities had diabetic retinopathy, nondiabetic vitreous hemorrhages, retinal detachments associated with vitreous hemorrhage, bands, or membranes, and intraocular foreign bodies or silicone oil. Patients with anterior segment opacities were treated for pupillary membranes resulting from surgical trauma or perforating injuries, and for complications following cataract extraction, such as capsule breakage and vitreous loss. Postoperatively, visual acuity improved in 68% of eyes with posterior segment opacities and in 85% of eyes with anterior segment opacities. Overall, visual acuity was 20/300 or better in 45% of eyes. There were only two intraoperative retinal tears and one postoperative rhegmatogenous retinal detachment."} {"id": "PMID:1258951", "title": "Visual loss after cardiopulmonary bypass.", "content": "Ten cases of visual loss ranging from total blindness to a brief period of transient ischemic attacks occurred after cardiopulmonary bypass. Brain scan studies indicated occipital cortical infarction as the cause. Thrombosis, embolization, and selective laminar cortical necrosis due to cerebral anoxia were possible mechanisms.", "contents": "Visual loss after cardiopulmonary bypass. Ten cases of visual loss ranging from total blindness to a brief period of transient ischemic attacks occurred after cardiopulmonary bypass. Brain scan studies indicated occipital cortical infarction as the cause. Thrombosis, embolization, and selective laminar cortical necrosis due to cerebral anoxia were possible mechanisms."} {"id": "PMID:1258952", "title": "Surgical treatment of true Brown's syndrome.", "content": "In 1950 H. W. Brown reported the superior oblique tendon sheath syndrome and cut the sheath as treatment for the condition. My results (as well as those of other surgeons) with similar surgery have been disappointing. Consequently, I carried out different operations consisting of Z tenotomy of superior oblique tendon in nine patients, split tendon lengthening in two patients, complete tenotomy in 16 patients, and a tenectomy in two patients. One of the latter was done on a patient after an unsatisfactory tenotomy where I missed the tendon. Tenotomy of the superior oblique tendon gave the best results. Experiments with the superior oblique tendon in cadavers several hours after death showed that after cutting the tendon just medial to the superior rectus muscle, the cut end of the tendon moved medially only about 8 to 10 mm due to restrictions of the capsular attachments to the trochlea. The cause of \"true\" Brown's syndrome is a tight tendon, and a safe and effective surgical treatment consists of cutting it just medial to the superior rectus muscle.", "contents": "Surgical treatment of true Brown's syndrome. In 1950 H. W. Brown reported the superior oblique tendon sheath syndrome and cut the sheath as treatment for the condition. My results (as well as those of other surgeons) with similar surgery have been disappointing. Consequently, I carried out different operations consisting of Z tenotomy of superior oblique tendon in nine patients, split tendon lengthening in two patients, complete tenotomy in 16 patients, and a tenectomy in two patients. One of the latter was done on a patient after an unsatisfactory tenotomy where I missed the tendon. Tenotomy of the superior oblique tendon gave the best results. Experiments with the superior oblique tendon in cadavers several hours after death showed that after cutting the tendon just medial to the superior rectus muscle, the cut end of the tendon moved medially only about 8 to 10 mm due to restrictions of the capsular attachments to the trochlea. The cause of \"true\" Brown's syndrome is a tight tendon, and a safe and effective surgical treatment consists of cutting it just medial to the superior rectus muscle."} {"id": "PMID:1258953", "title": "Saccadic velocity measurements in internuclear ophthalmoplegia.", "content": "Five patients with internuclear ophthalmoplegia had horizontal saccades measured by electro-oculography. In all patients, abduction saccadic velocities were normal while adduction saccades were slowed either binocularly or monocularly. In one patient, adduction saccades were reduced in velocity, even though full adduction was present. Saccadic velocity measurements may be helpful in diagnosing internuclear ophthalmoplegia, especially in the early or subclinical case. As bilateral internuclear ophthalmoplegia frequently suggests multiple sclerosis, prolonged examination with more sophisticated and difficult diagnostic tests is avoided.", "contents": "Saccadic velocity measurements in internuclear ophthalmoplegia. Five patients with internuclear ophthalmoplegia had horizontal saccades measured by electro-oculography. In all patients, abduction saccadic velocities were normal while adduction saccades were slowed either binocularly or monocularly. In one patient, adduction saccades were reduced in velocity, even though full adduction was present. Saccadic velocity measurements may be helpful in diagnosing internuclear ophthalmoplegia, especially in the early or subclinical case. As bilateral internuclear ophthalmoplegia frequently suggests multiple sclerosis, prolonged examination with more sophisticated and difficult diagnostic tests is avoided."} {"id": "PMID:1258954", "title": "Familial nanophthalmos.", "content": "Four members of one sibship had microphthalmos with fundi having an irregular \"rippled* appearance with alternating light and dark red coloration. Fluorescein angiography revealed patchy choriocapillaris perfusion with unusually rapid diffusion into the retina. Genealogic and geographic data strongly suggest autosomal-recessive inheritance. Only one patient developed glaucoma. The unique combination of abnormalities in this family suggests that a new recessive mutation may be responsible.", "contents": "Familial nanophthalmos. Four members of one sibship had microphthalmos with fundi having an irregular \"rippled* appearance with alternating light and dark red coloration. Fluorescein angiography revealed patchy choriocapillaris perfusion with unusually rapid diffusion into the retina. Genealogic and geographic data strongly suggest autosomal-recessive inheritance. Only one patient developed glaucoma. The unique combination of abnormalities in this family suggests that a new recessive mutation may be responsible."} {"id": "PMID:1258955", "title": "Corneal distribution of subconjunctival antibiotics.", "content": "Radioactive carbon-labeled penicillin G, chloramphenicol, or gentamicin were injected subconjunctivally into rabbit eyes. The distribution of antibiotics throughout the cornea was determined in relation to the injection site; aqueous humor levels were also measured. For chloramphenicol, the highest drug concentrations in the cornea were adjacent to the injection site; levels decreased as the distance from the injection site increased. For penicillin G and gentamicin, highest corneal levels were adjacent to the injection site. Levels were lowest in the central cornea but increased in the peripheral cornea, 180 degrees opposite the injection site. For all antibiotics, therapeutic levels were reached throughout the cornea irrespective of the injection site. Corneal values for all drugs were consistently higher than aqueous humor values. These results suggest that in the treatment of corneal ulcers the choice of subconjunctival injection site is not important.", "contents": "Corneal distribution of subconjunctival antibiotics. Radioactive carbon-labeled penicillin G, chloramphenicol, or gentamicin were injected subconjunctivally into rabbit eyes. The distribution of antibiotics throughout the cornea was determined in relation to the injection site; aqueous humor levels were also measured. For chloramphenicol, the highest drug concentrations in the cornea were adjacent to the injection site; levels decreased as the distance from the injection site increased. For penicillin G and gentamicin, highest corneal levels were adjacent to the injection site. Levels were lowest in the central cornea but increased in the peripheral cornea, 180 degrees opposite the injection site. For all antibiotics, therapeutic levels were reached throughout the cornea irrespective of the injection site. Corneal values for all drugs were consistently higher than aqueous humor values. These results suggest that in the treatment of corneal ulcers the choice of subconjunctival injection site is not important."} {"id": "PMID:1258956", "title": "Specular microscopy of human corneal endothelium in vivo.", "content": "A clinical specular microscope used in the routine examination fo the corneal endothelium of 40 patients at high magnification, without inconvenience or discomfort to the patients, detected endothelial damage or disease that was not seen by slit-lamp examination. A statistically significant decrease (P less than .001) in the number of central endothelial cells with age was documented.", "contents": "Specular microscopy of human corneal endothelium in vivo. A clinical specular microscope used in the routine examination fo the corneal endothelium of 40 patients at high magnification, without inconvenience or discomfort to the patients, detected endothelial damage or disease that was not seen by slit-lamp examination. A statistically significant decrease (P less than .001) in the number of central endothelial cells with age was documented."} {"id": "PMID:1258957", "title": "Surface ultrastructure in alkali-burned rabbit corneas.", "content": "The scanning electron microscope was used to follow morphologic events after alkali burn of rabbit corneas. Immediately after a burn there was extensive destruction and shrinkage of the epithelial cells. In subsequent healing, the regenerated superficial cells were morphologically abnormal and possed multiloculated cysts; three months later the normal polygonal packing of cells was not observed. Although the shape of these cells was irregular, microprojections were present on the cell surface. Basal cells were usually observed at the edge of an epithelial defect, an area where the epithelium was easily detached from the basement membrane. In long-standing epithelial defects, the basement membrane became eroded in a spot-like manner after about two weeks. Eventually, when a frank stromal ulcer had formed, bundles of collagen fibrils were visible in a meshwork-like fashion. These changes did not seem to be caused by the direct action of alkali but rather by latent secondary factors that took days or weeks to activate.", "contents": "Surface ultrastructure in alkali-burned rabbit corneas. The scanning electron microscope was used to follow morphologic events after alkali burn of rabbit corneas. Immediately after a burn there was extensive destruction and shrinkage of the epithelial cells. In subsequent healing, the regenerated superficial cells were morphologically abnormal and possed multiloculated cysts; three months later the normal polygonal packing of cells was not observed. Although the shape of these cells was irregular, microprojections were present on the cell surface. Basal cells were usually observed at the edge of an epithelial defect, an area where the epithelium was easily detached from the basement membrane. In long-standing epithelial defects, the basement membrane became eroded in a spot-like manner after about two weeks. Eventually, when a frank stromal ulcer had formed, bundles of collagen fibrils were visible in a meshwork-like fashion. These changes did not seem to be caused by the direct action of alkali but rather by latent secondary factors that took days or weeks to activate."} {"id": "PMID:1258958", "title": "Disinsertion of the aponeurosis of the levator palpebrae superioris muscle after cataract extraction.", "content": "Surgical exploration of the upper eyelid was undertaken in two patients who developed blepharoptosis after cataract extraction. Disinsertion of the aponeurosis of the levator palpebrae superioris muscle from its epitarsal attachments was discovered and repaired in each patient to correct the blepharoptosis.", "contents": "Disinsertion of the aponeurosis of the levator palpebrae superioris muscle after cataract extraction. Surgical exploration of the upper eyelid was undertaken in two patients who developed blepharoptosis after cataract extraction. Disinsertion of the aponeurosis of the levator palpebrae superioris muscle from its epitarsal attachments was discovered and repaired in each patient to correct the blepharoptosis."} {"id": "PMID:1258959", "title": "Increased intraocular pressure after third ventricle injections of prostaglandin E1 and arachidonic acid.", "content": "Prostaglandin E1 administered into the third ventricle of rabbits produced increased intraocular pressure and body temperature. Similar responses were observed after third ventricle instillation of arachidonic acid, a precursor of prostaglandin E2. Increase of body temperature occurred with lower doses of prostaglandin E1 and arachidonic acid while the intraocular pressure response required larger amounts of these drugs. Pretreatment with aspirin rectal suppositories had no effect on the third ventricle responses induced by prostaglandin E1. Aspirin pretreatment before third ventricle instillation of arachidonic acid blocked the increases of intraocular pressure and temperature.", "contents": "Increased intraocular pressure after third ventricle injections of prostaglandin E1 and arachidonic acid. Prostaglandin E1 administered into the third ventricle of rabbits produced increased intraocular pressure and body temperature. Similar responses were observed after third ventricle instillation of arachidonic acid, a precursor of prostaglandin E2. Increase of body temperature occurred with lower doses of prostaglandin E1 and arachidonic acid while the intraocular pressure response required larger amounts of these drugs. Pretreatment with aspirin rectal suppositories had no effect on the third ventricle responses induced by prostaglandin E1. Aspirin pretreatment before third ventricle instillation of arachidonic acid blocked the increases of intraocular pressure and temperature."} {"id": "PMID:1258960", "title": "Hemorrhage into the lens as a complication of glaucoma surgery.", "content": "Intralenticular hemorrhage is a rare complication of glaucoma surgery. In a 45-year-old man, the intralenticular blood caused loss of the red reflex from the fundus postoperatively. Clinically, hemorrhage into the lens has usually been misdiagnosed initially as a hyphema.", "contents": "Hemorrhage into the lens as a complication of glaucoma surgery. Intralenticular hemorrhage is a rare complication of glaucoma surgery. In a 45-year-old man, the intralenticular blood caused loss of the red reflex from the fundus postoperatively. Clinically, hemorrhage into the lens has usually been misdiagnosed initially as a hyphema."} {"id": "PMID:1258961", "title": "Prisms for inspection of a seesaw nystagmus.", "content": "Two eyes may be simultaneously viewed one above the other by using an arrangement of two prisms with their bases arranged to the right and to the left. When these prisms are placed in front of the glabella and tilted slightly clockwise it is possible to view both eyes simultaneously and appreciate the seesaw motion of a nystagmus.", "contents": "Prisms for inspection of a seesaw nystagmus. Two eyes may be simultaneously viewed one above the other by using an arrangement of two prisms with their bases arranged to the right and to the left. When these prisms are placed in front of the glabella and tilted slightly clockwise it is possible to view both eyes simultaneously and appreciate the seesaw motion of a nystagmus."} {"id": "PMID:1258967", "title": "Comprehensive evaluation of basic living skills.", "content": "In this paper a rationale is established for an evaluation of basic living skills for chronic psychiatric patients living in mental institutions, and a comprehensive evaluation is presented. The advantages of this battery of tests over currently used activities of daily living scales are: it is specifically designed for psychiatric patients, it tests a wide range of skills, the items are graded in complexity, it can be administered in full or in part, and it has a scoring system and a summary that indicates the patient's functional status. The information gained from the evaluation improves staff communication about patient care and aids in the planning of the patient's future placement or treatment situation.", "contents": "Comprehensive evaluation of basic living skills. In this paper a rationale is established for an evaluation of basic living skills for chronic psychiatric patients living in mental institutions, and a comprehensive evaluation is presented. The advantages of this battery of tests over currently used activities of daily living scales are: it is specifically designed for psychiatric patients, it tests a wide range of skills, the items are graded in complexity, it can be administered in full or in part, and it has a scoring system and a summary that indicates the patient's functional status. The information gained from the evaluation improves staff communication about patient care and aids in the planning of the patient's future placement or treatment situation."} {"id": "PMID:1258968", "title": "Cosmetic prosthesis for traumatic defect of the leg.", "content": "The procedure described above requires two clinic visits: the initial visit for measuring and casting; the second visit for fitting, additional contouring, if necessary, and delivering the prosthesis to the patient. This prosthesis fits into the defect and is kept in place by wearing a support sock. There is minimal chance of slipping since it conforms to the defect and is also extremely light-weight. The prosthesis is confortable and allows the child to sit, kneel, and run without difficulty.", "contents": "Cosmetic prosthesis for traumatic defect of the leg. The procedure described above requires two clinic visits: the initial visit for measuring and casting; the second visit for fitting, additional contouring, if necessary, and delivering the prosthesis to the patient. This prosthesis fits into the defect and is kept in place by wearing a support sock. There is minimal chance of slipping since it conforms to the defect and is also extremely light-weight. The prosthesis is confortable and allows the child to sit, kneel, and run without difficulty."} {"id": "PMID:1258970", "title": "Adolescent role assessment.", "content": "Adolescence is a complex period when children are expected to shed their dependencies and achieve a level of independence as adults. Frequently, adult independence is achieved through the occupational role where individuals recognize personal assets and liabilities and participate cooperatively in the society. The decision-making process that guides adolescents in the search for an occupational role is occupational choice. This paper traces the development of skills necessary for the occupational choice process. An instrument is presented that attempts to identify deficiencies in the occupational choice process and to provide content for occupational therapy intervention. Its usefulness in screening deviant adolescents in order to identify those who may be at high risk in the occupational choice process is discussed.", "contents": "Adolescent role assessment. Adolescence is a complex period when children are expected to shed their dependencies and achieve a level of independence as adults. Frequently, adult independence is achieved through the occupational role where individuals recognize personal assets and liabilities and participate cooperatively in the society. The decision-making process that guides adolescents in the search for an occupational role is occupational choice. This paper traces the development of skills necessary for the occupational choice process. An instrument is presented that attempts to identify deficiencies in the occupational choice process and to provide content for occupational therapy intervention. Its usefulness in screening deviant adolescents in order to identify those who may be at high risk in the occupational choice process is discussed."} {"id": "PMID:1258971", "title": "Hand skill measurement: a gauge for treatment.", "content": "Objective measurements of performance are vital with the increasing necessity to justify the need for occupational therapy services, and to conduct studies that measure the effectiveness of treatment procedures. This paper reports on a measurement of hand skill that was standardized by comparing hand skill performance among the able-bodied, or normal, population. The performance on this test o patients with various types of disabilities and the implications for treatment are discussed. For the paraplegic, the hand skill test indicates the need for occupational therapy services; for the quadriplegic, the test measures the effectiveness of functional orthotic devices; and for the hemiplegic, the hand skill test determines the potential for success in one aspect of self-care, dressing.", "contents": "Hand skill measurement: a gauge for treatment. Objective measurements of performance are vital with the increasing necessity to justify the need for occupational therapy services, and to conduct studies that measure the effectiveness of treatment procedures. This paper reports on a measurement of hand skill that was standardized by comparing hand skill performance among the able-bodied, or normal, population. The performance on this test o patients with various types of disabilities and the implications for treatment are discussed. For the paraplegic, the hand skill test indicates the need for occupational therapy services; for the quadriplegic, the test measures the effectiveness of functional orthotic devices; and for the hemiplegic, the hand skill test determines the potential for success in one aspect of self-care, dressing."} {"id": "PMID:1258972", "title": "Theoretical and clinical approaches to the treatment of adolescent drug addiction.", "content": "Psychologists, social workers, addiction specialists, and occupational therapists often find themselves faced with clients who not only are addicted but also have personal, family, and social problems. These combined problems make the drug-abusing client an extremely difficult one to work with. Occupational therapists have a particular challenge in that they must not only understand and analyze their clients' occupational behavior but also their needs as addicts. This paper describes an approach to adolescent addiction that presents a clinical and theoretical consideration that could be helpful to professionals who work with addicted or drug-abusing clients. In the approach a fusion must be made between the client and the therapist or treatment program. The fusion is temporary but long enough to provide opportunities for clients to work through their feelings of anger, aggression, and sadism, as well as their ego and superego problems. To understand all aspects of their use of drugs, an easily memorized two-dimensional scheme is drawn by the client and therapist together and is used to formulate a treatment plan. Separation from the therapist or program is an essential part of treatment. At this time the client is given the kind of emotional support required to establish new relationships.", "contents": "Theoretical and clinical approaches to the treatment of adolescent drug addiction. Psychologists, social workers, addiction specialists, and occupational therapists often find themselves faced with clients who not only are addicted but also have personal, family, and social problems. These combined problems make the drug-abusing client an extremely difficult one to work with. Occupational therapists have a particular challenge in that they must not only understand and analyze their clients' occupational behavior but also their needs as addicts. This paper describes an approach to adolescent addiction that presents a clinical and theoretical consideration that could be helpful to professionals who work with addicted or drug-abusing clients. In the approach a fusion must be made between the client and the therapist or treatment program. The fusion is temporary but long enough to provide opportunities for clients to work through their feelings of anger, aggression, and sadism, as well as their ego and superego problems. To understand all aspects of their use of drugs, an easily memorized two-dimensional scheme is drawn by the client and therapist together and is used to formulate a treatment plan. Separation from the therapist or program is an essential part of treatment. At this time the client is given the kind of emotional support required to establish new relationships."} {"id": "PMID:1258973", "title": "Comprehensive occupational therapy evaluation scale.", "content": "This paper presents the Comprehensive Occupational Therapy Evaluation Scale (COTE Scale) for use by occupational therapists in short-term, acute-care psychiatric facilities. The scale defines 25 behaviors that occur in and are particularly relevant to the practice of occupational therapy. The scale is used as an initial evaluation, as a record of patient progress, and as a means of communicating the evaluation, progress, and treatment to other hospital departments. Ratings of patients that indicate improvement and readiness for discharge are supported by the evaluations of other disciplines.", "contents": "Comprehensive occupational therapy evaluation scale. This paper presents the Comprehensive Occupational Therapy Evaluation Scale (COTE Scale) for use by occupational therapists in short-term, acute-care psychiatric facilities. The scale defines 25 behaviors that occur in and are particularly relevant to the practice of occupational therapy. The scale is used as an initial evaluation, as a record of patient progress, and as a means of communicating the evaluation, progress, and treatment to other hospital departments. Ratings of patients that indicate improvement and readiness for discharge are supported by the evaluations of other disciplines."} {"id": "PMID:1258974", "title": "The influence of aspirin and indomethacin on the platelet contractile wave.", "content": "Recent evidence suggests that a short-lived product of prostaglandin biosynthesis produced on the addition of arachidonic acid to platelet microsomes is involved in physiologic platelet aggregation and mediates the release reaction by producing the platelet contractile wave. An important corollary of this hypothesis is that aspirin and indomethacin, inhibitors of prostaglandin synthesis, should block the platelet contractile process produced by agents which can initiate platelet aggregation. The present study tested this hypothesis and found that aspirin and indomethacin were, indeed, potent inhibitors of the platelet contractile wave stimulated by collagen and epinephrine, but largely failed to inhibit internal transformation induced by thrombin and ADP. The findings confirm the hypothesis that a prostaglandin produced endogenously by platelets initiates platelet contraction and suggests that ADP and thrombin have the ability to stimulate the platelet contractile apparatus by an alternate mechanism not dependent on prostaglandin synthesis.", "contents": "The influence of aspirin and indomethacin on the platelet contractile wave. Recent evidence suggests that a short-lived product of prostaglandin biosynthesis produced on the addition of arachidonic acid to platelet microsomes is involved in physiologic platelet aggregation and mediates the release reaction by producing the platelet contractile wave. An important corollary of this hypothesis is that aspirin and indomethacin, inhibitors of prostaglandin synthesis, should block the platelet contractile process produced by agents which can initiate platelet aggregation. The present study tested this hypothesis and found that aspirin and indomethacin were, indeed, potent inhibitors of the platelet contractile wave stimulated by collagen and epinephrine, but largely failed to inhibit internal transformation induced by thrombin and ADP. The findings confirm the hypothesis that a prostaglandin produced endogenously by platelets initiates platelet contraction and suggests that ADP and thrombin have the ability to stimulate the platelet contractile apparatus by an alternate mechanism not dependent on prostaglandin synthesis."} {"id": "PMID:1258975", "title": "Ultrastructural cytochemistry of the ischemic (endocrine) kidney.", "content": "Partial ligation of the aorta between the renal arteries induces marked atrophy of the cortical tubules (including the macula densa) of the left (endocrine) kidney with a remarkable increase in the number and granularity of hypersecretory juxtaglomerular granulated cells (JGC) which are found not only at the glomerular pole of arterioles but also in the walls of arteries and arterioles far removed from the glomerulus. Staining of fine sections of Araldite-embedded endocrine kidneys according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery reveals abundant glycogen in the JGC and less in the blood vessels and tubules. Juxtaglomerular granules are argentaphobic, but their rim is positively stained when ultrathin sections of glutaraldehyde-fixed, glycol methacrylate-embedded kidneys are exposed to phosphotungstic acid at a low pH. A positive reaction is also shown by the cell coat and lysosomes of JGC as well as by the thickened basal lamina, cell coat, cytosomes, and cytosegresomes of the atrophic tubules. Atrophy is most pronounced in the proximal convoluted tubules, which lose their apical microvilli, their basal infoldings and the majority of their mitochondria and cytosomes.", "contents": "Ultrastructural cytochemistry of the ischemic (endocrine) kidney. Partial ligation of the aorta between the renal arteries induces marked atrophy of the cortical tubules (including the macula densa) of the left (endocrine) kidney with a remarkable increase in the number and granularity of hypersecretory juxtaglomerular granulated cells (JGC) which are found not only at the glomerular pole of arterioles but also in the walls of arteries and arterioles far removed from the glomerulus. Staining of fine sections of Araldite-embedded endocrine kidneys according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery reveals abundant glycogen in the JGC and less in the blood vessels and tubules. Juxtaglomerular granules are argentaphobic, but their rim is positively stained when ultrathin sections of glutaraldehyde-fixed, glycol methacrylate-embedded kidneys are exposed to phosphotungstic acid at a low pH. A positive reaction is also shown by the cell coat and lysosomes of JGC as well as by the thickened basal lamina, cell coat, cytosomes, and cytosegresomes of the atrophic tubules. Atrophy is most pronounced in the proximal convoluted tubules, which lose their apical microvilli, their basal infoldings and the majority of their mitochondria and cytosomes."} {"id": "PMID:1258976", "title": "Inflammatory sequences in acute pulmonary radiation injury.", "content": "The histopathologic events in the developing acute pulmonary inflammatory reaction to inhaled particles of Yttrium 90 are detailed. In animals that died or were sacrificed during the first year after inhalation exposure, microscopic findings of acute inflammation predominated and included vascular congestion; stasis, focal hemorrhage; edema; various inflammatory cell infiltrates; cytolysis and desquamation of bronchiolar and alveolar epithelium followed by regeneration; vascular injury and repair; and the eventual development of pulmonary fibrosis. Accumulation of alveolar fibrin deposits was an additional characteristic, though not a constant feature of the early stages of radiation pneumonitis. In addition to the direct effects of radiation on pulmonary cell populations, the histopathologic findings were suggestive of diverse activation of various cellular and humoral mediation systems in their pathogenesis. The potential interrelationships of systems responsible for increased vascular permeability, coagulation and fibrinolysis, chemotaxis, and direct cellular injury were discussed and related to the pathogenesis of the microscopic findings characteristic of early pulmonary radiation injury.", "contents": "Inflammatory sequences in acute pulmonary radiation injury. The histopathologic events in the developing acute pulmonary inflammatory reaction to inhaled particles of Yttrium 90 are detailed. In animals that died or were sacrificed during the first year after inhalation exposure, microscopic findings of acute inflammation predominated and included vascular congestion; stasis, focal hemorrhage; edema; various inflammatory cell infiltrates; cytolysis and desquamation of bronchiolar and alveolar epithelium followed by regeneration; vascular injury and repair; and the eventual development of pulmonary fibrosis. Accumulation of alveolar fibrin deposits was an additional characteristic, though not a constant feature of the early stages of radiation pneumonitis. In addition to the direct effects of radiation on pulmonary cell populations, the histopathologic findings were suggestive of diverse activation of various cellular and humoral mediation systems in their pathogenesis. The potential interrelationships of systems responsible for increased vascular permeability, coagulation and fibrinolysis, chemotaxis, and direct cellular injury were discussed and related to the pathogenesis of the microscopic findings characteristic of early pulmonary radiation injury."} {"id": "PMID:1258977", "title": "The Chediak-Higashi (beige) mutation in two mouse strains. Allelism and similarity in lysosomal dysfunction.", "content": "A mutation called beige, with a phenotype similar to that of the human Chediak-Higashi syndrome, has occurred independently in two inbred strains of mice. Beige-J (bgj) occurred as a spontaneous mutation in the C57B1/6J strain and beige (bg) was radiation-induced in mice of heterogenous background which were then inbred as strain SB/Le (bg/bg), the subject of the present study. As in the previously characterized C57Bl/6J beige-J mutant, there is a correlation between abnormal lysosome structure and defective lysosome function in SB/Le beige mice. They secrete much less than normal amounts of lysosomal enzymes from proximal tubule cells and, hence, have increased lysosomal enzyme activity in kidney. In addition, after treatment of either beige strain with androgen, numerous giant beta-glucuronidase-containing lysosomes are present in kidney proximal tubule cells near the corticomedullary border. By directly measuring the rate of beta-glucuronidase synthesis in androgen-treated SB/Le beige mouse kidney, it was shown that the greater accumulation of this lysosomal enzyme in proximal tubule cells was not due to an increase in its rate of synthesis. Genetic analysis of the beige mutations in the two mutant strains demonstrated that both mutant genes are recessive and, in fact, are allelic. The results suggest that both beige strains are defective in intracellular motility of lysosomes and/or their fusion with cellular membranes, and that both mutant strains are suitable experimental models for the human Chediak-Higashi syndrome.", "contents": "The Chediak-Higashi (beige) mutation in two mouse strains. Allelism and similarity in lysosomal dysfunction. A mutation called beige, with a phenotype similar to that of the human Chediak-Higashi syndrome, has occurred independently in two inbred strains of mice. Beige-J (bgj) occurred as a spontaneous mutation in the C57B1/6J strain and beige (bg) was radiation-induced in mice of heterogenous background which were then inbred as strain SB/Le (bg/bg), the subject of the present study. As in the previously characterized C57Bl/6J beige-J mutant, there is a correlation between abnormal lysosome structure and defective lysosome function in SB/Le beige mice. They secrete much less than normal amounts of lysosomal enzymes from proximal tubule cells and, hence, have increased lysosomal enzyme activity in kidney. In addition, after treatment of either beige strain with androgen, numerous giant beta-glucuronidase-containing lysosomes are present in kidney proximal tubule cells near the corticomedullary border. By directly measuring the rate of beta-glucuronidase synthesis in androgen-treated SB/Le beige mouse kidney, it was shown that the greater accumulation of this lysosomal enzyme in proximal tubule cells was not due to an increase in its rate of synthesis. Genetic analysis of the beige mutations in the two mutant strains demonstrated that both mutant genes are recessive and, in fact, are allelic. The results suggest that both beige strains are defective in intracellular motility of lysosomes and/or their fusion with cellular membranes, and that both mutant strains are suitable experimental models for the human Chediak-Higashi syndrome."} {"id": "PMID:1258978", "title": "A light and electron microscopic analysis of gentamicin nephrotoxicity in rats.", "content": "The sequence of proximal tubular damage and repair after gentamicin sulfate administration was studied by light and electron microscopy in Fischer 344 rats. The drug was administered at a dose of 40 mg/kg for up to 14 days. Although epithelial destruction was progressive with time, the extent and degree of tubular damage varied among animals at each interval. Tubule regeneration began to occur by the tenth day despite continued drug administration. Regenerating cells appeared to originate from residual epithelial cells in areas of tubular damage. The morphologically immature regenerating cells are apparently metabolically immature as well and appear not to be susceptible to toxic effects of the drug. Tubules were repopulated by 3 days following cessation of gentamicin administration. Except for foci of tubular atrophy and interstitial fibrosis, cortical tissues were comparable to controls ultrastructurally at the end of 31 days.", "contents": "A light and electron microscopic analysis of gentamicin nephrotoxicity in rats. The sequence of proximal tubular damage and repair after gentamicin sulfate administration was studied by light and electron microscopy in Fischer 344 rats. The drug was administered at a dose of 40 mg/kg for up to 14 days. Although epithelial destruction was progressive with time, the extent and degree of tubular damage varied among animals at each interval. Tubule regeneration began to occur by the tenth day despite continued drug administration. Regenerating cells appeared to originate from residual epithelial cells in areas of tubular damage. The morphologically immature regenerating cells are apparently metabolically immature as well and appear not to be susceptible to toxic effects of the drug. Tubules were repopulated by 3 days following cessation of gentamicin administration. Except for foci of tubular atrophy and interstitial fibrosis, cortical tissues were comparable to controls ultrastructurally at the end of 31 days."} {"id": "PMID:1258982", "title": "The genetics of shovel shape in maxillary central incisors in man.", "content": "From dental casts of 94 parent-offspring and 127 full-sib pairs, sampled from two Chilean populations, shovelling indices are computed to measure the degree of shovelling of maxillary central incisors quantitatively. Genetic correlations are computed to determine the role of genetic factors in explaining the variation in this trait. Assuming only hereditary factors to be responsible for the transmission of shovel shape, 68% of total variability is ascribed to the additive effect of genes.", "contents": "The genetics of shovel shape in maxillary central incisors in man. From dental casts of 94 parent-offspring and 127 full-sib pairs, sampled from two Chilean populations, shovelling indices are computed to measure the degree of shovelling of maxillary central incisors quantitatively. Genetic correlations are computed to determine the role of genetic factors in explaining the variation in this trait. Assuming only hereditary factors to be responsible for the transmission of shovel shape, 68% of total variability is ascribed to the additive effect of genes."} {"id": "PMID:1258983", "title": "Relationship of body composition to somatotype.", "content": "The purpose of this study is to determine the relationship in college-aged women between somatotype using both Sheldon's ('69) and Heath and Carter's ('67) procedures, and body composition, as measured by whole-body 40K counting and body density. Sheldon's endomorphy is closely associated with height and weight; Heath and Carter's first component is significantly related to weight and body fatness. Lean body mass (LBM) as a weight or as a percent is not closely related to Sheldon's mesomorphy or Heath and Carter's second component. However, when LBM and height are used as independent variables to estimate somatotype, both variables are significantly related to Heath and Carter's second component, accounting for 61% of the variance. Thus Heath and Carter's second component is significantly associated with LBM for a given body height. Most of the variation in Sheldon's ectomorphy and Heath and Carter's third component can be accounted for by weight and height. Sheldon's somatotype for all three components is not as closely related to body composition as Heath-Carter's. Body composition, as measured by either 40K counting or body density, is found to be important in accounting for variation in Heath and Carter's first and second components.", "contents": "Relationship of body composition to somatotype. The purpose of this study is to determine the relationship in college-aged women between somatotype using both Sheldon's ('69) and Heath and Carter's ('67) procedures, and body composition, as measured by whole-body 40K counting and body density. Sheldon's endomorphy is closely associated with height and weight; Heath and Carter's first component is significantly related to weight and body fatness. Lean body mass (LBM) as a weight or as a percent is not closely related to Sheldon's mesomorphy or Heath and Carter's second component. However, when LBM and height are used as independent variables to estimate somatotype, both variables are significantly related to Heath and Carter's second component, accounting for 61% of the variance. Thus Heath and Carter's second component is significantly associated with LBM for a given body height. Most of the variation in Sheldon's ectomorphy and Heath and Carter's third component can be accounted for by weight and height. Sheldon's somatotype for all three components is not as closely related to body composition as Heath-Carter's. Body composition, as measured by either 40K counting or body density, is found to be important in accounting for variation in Heath and Carter's first and second components."} {"id": "PMID:1258984", "title": "The frequency of middle phalangeal hair in Saudi Arabia.", "content": "Middle phalangeal hair was found to be present in 71% if Saudi Arabian males. For those exhibiting this trait, the frequency of combinations of digits with hair was similar to the frequency in other populations.", "contents": "The frequency of middle phalangeal hair in Saudi Arabia. Middle phalangeal hair was found to be present in 71% if Saudi Arabian males. For those exhibiting this trait, the frequency of combinations of digits with hair was similar to the frequency in other populations."} {"id": "PMID:1258985", "title": "Newborn Brain: Body weight ratios.", "content": "Newborn brain:body weight ratios are generally considered to be constant in man. In autopsy studies many factors influence the measured weight of the brain, and therefore the conclusions based on such observations, including the gestational age of the material, the presence or absence of intrauterine growth retardation, and the cause of death. In this study these influences have been eliminated by careful selection of normally grown fullterm newborns not subject to the factors influencing brain weight. Using double logarithmic plots, brain size in fullterm newborns is found to be related to the 0.64 power of birth weight. There is a negative correlation between relative brain size and increasing fullterm birth size in man.", "contents": "Newborn Brain: Body weight ratios. Newborn brain:body weight ratios are generally considered to be constant in man. In autopsy studies many factors influence the measured weight of the brain, and therefore the conclusions based on such observations, including the gestational age of the material, the presence or absence of intrauterine growth retardation, and the cause of death. In this study these influences have been eliminated by careful selection of normally grown fullterm newborns not subject to the factors influencing brain weight. Using double logarithmic plots, brain size in fullterm newborns is found to be related to the 0.64 power of birth weight. There is a negative correlation between relative brain size and increasing fullterm birth size in man."} {"id": "PMID:1258986", "title": "The interaction between nonmetric and metric cranial variation.", "content": "Cranial discrete or 'epigenetic\" traits have been analyzed for interrelationships with measurements of the skull in a sample of American Negro males. Univariate t and multivariate T2 tests are used. It has been the previous consensus view that nonmetric and metric characters are unrelated. Statistically significant associations between the total of 50 discrete and 23 metrical characters, however, are much more frequent than would be expected through random distribution. Multivariate analysis supplements simpler statistics by synthesizing patterns of variation within regions of the skull, identifying many interrelations of skull size and shape with discrete traits. A low but observable general influence is exerted upon nonmetric morphology by metrical variation of the human skull (or vice versa).", "contents": "The interaction between nonmetric and metric cranial variation. Cranial discrete or 'epigenetic\" traits have been analyzed for interrelationships with measurements of the skull in a sample of American Negro males. Univariate t and multivariate T2 tests are used. It has been the previous consensus view that nonmetric and metric characters are unrelated. Statistically significant associations between the total of 50 discrete and 23 metrical characters, however, are much more frequent than would be expected through random distribution. Multivariate analysis supplements simpler statistics by synthesizing patterns of variation within regions of the skull, identifying many interrelations of skull size and shape with discrete traits. A low but observable general influence is exerted upon nonmetric morphology by metrical variation of the human skull (or vice versa)."} {"id": "PMID:1258987", "title": "Local cold exposure of Andean Indians during normal and simulated activities.", "content": "Thermal resonses of Andean Indians were measured during several customary tasks associated with cold exposure in the highlands of southern Peru. These included surface temperature measurements of women while they washed clothing in the river and similar measurements of men while they constructed a diversion channel in the same river. A third test measured the effects of alcohol consumption on body temperatures during light activity. Women maintained slightly warmer hand than foot temperatures. Men maintained nearly equal hand and foot temperatures during the exposure period. Among male subjects the foot rewarmed at a faster rate than the hand. The results from the field studies compared favorably with results from earlier laboratory exposure tests. Comparisons between the river water exposure tests for males and females showed a consistent pattern where females maintained warmer hand and foot temperatures than males. These findings were in accord with previous laboratory studies among Quechua Indians and with the findings reported for other ethnic groups who experience natural cold stress. Alcohol ingestion appeared to have minimal effect in mitigating cold stress response during light activity. This finding was counter to earlier laboratory tests of resting subjects.", "contents": "Local cold exposure of Andean Indians during normal and simulated activities. Thermal resonses of Andean Indians were measured during several customary tasks associated with cold exposure in the highlands of southern Peru. These included surface temperature measurements of women while they washed clothing in the river and similar measurements of men while they constructed a diversion channel in the same river. A third test measured the effects of alcohol consumption on body temperatures during light activity. Women maintained slightly warmer hand than foot temperatures. Men maintained nearly equal hand and foot temperatures during the exposure period. Among male subjects the foot rewarmed at a faster rate than the hand. The results from the field studies compared favorably with results from earlier laboratory exposure tests. Comparisons between the river water exposure tests for males and females showed a consistent pattern where females maintained warmer hand and foot temperatures than males. These findings were in accord with previous laboratory studies among Quechua Indians and with the findings reported for other ethnic groups who experience natural cold stress. Alcohol ingestion appeared to have minimal effect in mitigating cold stress response during light activity. This finding was counter to earlier laboratory tests of resting subjects."} {"id": "PMID:1258988", "title": "Finding from Asia, Australia, Europe, and North Amercia on secular change in mean height of children, youths, and young adults.", "content": "Studies conducted during the past century in Australia, Canada, Japan, Norway and the United States indicate that the magnitude of secular increase in mean height rose with advancing age from childhood to mid-adolescence. Comparisons for a period approximating two-thirds of a century yield average increases in mean height of 12.2 cm for female youths age 12 years, and 12.5 cm for male youths age 14 years; for the same calendar span, the amount of secular increase in mean height declines from mid-adolescence to early adulthood. Comparisons of Belgian females, spanning a period approximating 130 years, yield increases in mean height of 18.1 cm at age 12 years, 11.9 cm at age 16 years, and 3.7 cm in early adulthood. For a period of 90 years, increases obtained on United States White males are 14.8 cm at age 14 years, 8.8 cm at age 17 years, and 5.3 cm in early adulthood. These and other displayed findings show clearly that the search for causes of secular change should take particular account of a phenomenon widespread among human populations, i.e., the phenomenon of childhood and early adolescent growth in body height proceeding at a faster pace in recent decades than about a century ago.", "contents": "Finding from Asia, Australia, Europe, and North Amercia on secular change in mean height of children, youths, and young adults. Studies conducted during the past century in Australia, Canada, Japan, Norway and the United States indicate that the magnitude of secular increase in mean height rose with advancing age from childhood to mid-adolescence. Comparisons for a period approximating two-thirds of a century yield average increases in mean height of 12.2 cm for female youths age 12 years, and 12.5 cm for male youths age 14 years; for the same calendar span, the amount of secular increase in mean height declines from mid-adolescence to early adulthood. Comparisons of Belgian females, spanning a period approximating 130 years, yield increases in mean height of 18.1 cm at age 12 years, 11.9 cm at age 16 years, and 3.7 cm in early adulthood. For a period of 90 years, increases obtained on United States White males are 14.8 cm at age 14 years, 8.8 cm at age 17 years, and 5.3 cm in early adulthood. These and other displayed findings show clearly that the search for causes of secular change should take particular account of a phenomenon widespread among human populations, i.e., the phenomenon of childhood and early adolescent growth in body height proceeding at a faster pace in recent decades than about a century ago."} {"id": "PMID:1258989", "title": "Influence of physical activity on stability of somatotypes in boys.", "content": "The purpose of this study is to examine the stability of somatotypes of boys with different activity levels followed longitudinally for eight years. Thirty-nine boys ated 11 were somatotyped annually (until 18 years) using the Heath-Carter anthropometric rating method. Three sub-groups were formed according to their levels of systematic physical activity designated High, Moderate, and Low Activity. There were no differences in somatochart distributions of the Total Group, but there were considerable individual changes which cancelled each other in group comparisons. All boys changed their somatotype ratings at least once and 67% changed in component dominance. The inter-age correlations for the components were generally of poor prediction value, and the somatotype migratory distances showed considerable variation. The Total Group means differed on three components and this was attributed to differences within the Moderate Activity Group, the only sub-groups to differ. It was concluded that changes occur in somatotypes of adolescent boys, but the influence of physical activity on the changes is inconclusive.", "contents": "Influence of physical activity on stability of somatotypes in boys. The purpose of this study is to examine the stability of somatotypes of boys with different activity levels followed longitudinally for eight years. Thirty-nine boys ated 11 were somatotyped annually (until 18 years) using the Heath-Carter anthropometric rating method. Three sub-groups were formed according to their levels of systematic physical activity designated High, Moderate, and Low Activity. There were no differences in somatochart distributions of the Total Group, but there were considerable individual changes which cancelled each other in group comparisons. All boys changed their somatotype ratings at least once and 67% changed in component dominance. The inter-age correlations for the components were generally of poor prediction value, and the somatotype migratory distances showed considerable variation. The Total Group means differed on three components and this was attributed to differences within the Moderate Activity Group, the only sub-groups to differ. It was concluded that changes occur in somatotypes of adolescent boys, but the influence of physical activity on the changes is inconclusive."} {"id": "PMID:1258990", "title": "The genetic structure of finland.", "content": "The Finnish gene pool derives primarily from a relatively homogeneous Finno-Ugric population established during the Iron Age (100 B.C.-800 A.D.) in the southwest and southeast of Finland. Gene flow from Sweden to the southwest coastal areas, dating from prehistoric times, as well as the patterns of settlement and migration throughout Finland during the past 1000 years, appear to have been the major biosocial factors underlying the genetic structure of the contemporary population. Analysis of genetic variation and covariation at nine polymorphic loci in a large random sample of rural Finns, partitioned into either 8 countries or 27 geographic districts, showed that all of the essential features of the genetic structure suggested by the archaeological and historical data could be distinguished. Procedures for obtaining inference on the genetic structure of such a population are reviewed, including coefficients of similarity and (genetic) distance among subpopulations, the relation between linear or planar geographic structure and genetic covariation, and the methods for describing allelic differentiation. Bias resulting from the inappropriate assumption of a simple phylogenetic model can be substantial, expecially for the analysis of isolation by distance; procedures for avoiding misleading inference on the genetic structure are demonstrated.", "contents": "The genetic structure of finland. The Finnish gene pool derives primarily from a relatively homogeneous Finno-Ugric population established during the Iron Age (100 B.C.-800 A.D.) in the southwest and southeast of Finland. Gene flow from Sweden to the southwest coastal areas, dating from prehistoric times, as well as the patterns of settlement and migration throughout Finland during the past 1000 years, appear to have been the major biosocial factors underlying the genetic structure of the contemporary population. Analysis of genetic variation and covariation at nine polymorphic loci in a large random sample of rural Finns, partitioned into either 8 countries or 27 geographic districts, showed that all of the essential features of the genetic structure suggested by the archaeological and historical data could be distinguished. Procedures for obtaining inference on the genetic structure of such a population are reviewed, including coefficients of similarity and (genetic) distance among subpopulations, the relation between linear or planar geographic structure and genetic covariation, and the methods for describing allelic differentiation. Bias resulting from the inappropriate assumption of a simple phylogenetic model can be substantial, expecially for the analysis of isolation by distance; procedures for avoiding misleading inference on the genetic structure are demonstrated."} {"id": "PMID:1258991", "title": "The cnemic index: a criktique.", "content": "The accuracy of the cnemic index is questioned. Excessive random variation is found to be present in the datum for this index, the nutrient foramen. It is suggested that the index be taken at a fixed location on the tibial shaft. A new index, the cnemic index (one-third), is proposed.", "contents": "The cnemic index: a criktique. The accuracy of the cnemic index is questioned. Excessive random variation is found to be present in the datum for this index, the nutrient foramen. It is suggested that the index be taken at a fixed location on the tibial shaft. A new index, the cnemic index (one-third), is proposed."} {"id": "PMID:1258992", "title": "P.T.C. tasting among three Indian groups of Nicaragua.", "content": "Ninety-six Miskito, 85 Sumo and 79 Rama Indians were tested for P.T.C. taste ability according to a modification of Harris and Kalmus' sorting technique. Miskito's \"non-taster\" high frequency approach values reported for some highly inbred Central and South American Indian populations, while Rama's and Sumo's figures appear in aggrement with values reported for other relatively pure Amerindians.", "contents": "P.T.C. tasting among three Indian groups of Nicaragua. Ninety-six Miskito, 85 Sumo and 79 Rama Indians were tested for P.T.C. taste ability according to a modification of Harris and Kalmus' sorting technique. Miskito's \"non-taster\" high frequency approach values reported for some highly inbred Central and South American Indian populations, while Rama's and Sumo's figures appear in aggrement with values reported for other relatively pure Amerindians."} {"id": "PMID:1258993", "title": "Advanced weathering cracks as an improvement on split-line preparations for analysis of structural orientation in compact bone.", "content": "Weathering cracks have been demonstrated to be equivalent to split-lines in compact bone. The amount of cracking becomes more extensive with time. Advanced weathering cracks have the potential for giving more complete information on orientation patterns than split-lines. They can also be superior in accuracy and objectivity of results obtained, in preserving the original condition of the bone, and in elimination of much of the work involved in making split-line preparations.", "contents": "Advanced weathering cracks as an improvement on split-line preparations for analysis of structural orientation in compact bone. Weathering cracks have been demonstrated to be equivalent to split-lines in compact bone. The amount of cracking becomes more extensive with time. Advanced weathering cracks have the potential for giving more complete information on orientation patterns than split-lines. They can also be superior in accuracy and objectivity of results obtained, in preserving the original condition of the bone, and in elimination of much of the work involved in making split-line preparations."} {"id": "PMID:1258999", "title": "Dietary regulation of liver and muscle transport of amino acid.", "content": "Distribution ratios (intracellular concn/extracellular concn) of alpha-amino isobutyric acid (AIB) after intravenous injection were determined in fed, 12-h, 1-day, and 5-day starved rats. Progressive increases (over fourfold) in the distribution ratios of AIB in the liver and progressive decreases (over threefold) in the gastrocnemius muscle occurred within these periods. On full day of protein deprivation was without effect on AIB distribution ratios, but after 5 days it produced an increased distribution ratio of AIB in the liver (twofold), without affecting that of the muscle. A sudden increase in hepatic glucose output, induced by phlorizin, was followed by an increase in the liver distribution ratio of AIB. In starvation the increase in plasma concentration of glucagon and decrease in insulin level preceded the changes in AIB distribution ratios; in protein deprivation there was no change in plasma concentrations of these hormones. It is concluded that caloric restriction profoundly affects amino acid transport by the liver and by the skeletal muscle. These transport changes would enhance the availability of substrates for increased gluconeogenesis during starvation.", "contents": "Dietary regulation of liver and muscle transport of amino acid. Distribution ratios (intracellular concn/extracellular concn) of alpha-amino isobutyric acid (AIB) after intravenous injection were determined in fed, 12-h, 1-day, and 5-day starved rats. Progressive increases (over fourfold) in the distribution ratios of AIB in the liver and progressive decreases (over threefold) in the gastrocnemius muscle occurred within these periods. On full day of protein deprivation was without effect on AIB distribution ratios, but after 5 days it produced an increased distribution ratio of AIB in the liver (twofold), without affecting that of the muscle. A sudden increase in hepatic glucose output, induced by phlorizin, was followed by an increase in the liver distribution ratio of AIB. In starvation the increase in plasma concentration of glucagon and decrease in insulin level preceded the changes in AIB distribution ratios; in protein deprivation there was no change in plasma concentrations of these hormones. It is concluded that caloric restriction profoundly affects amino acid transport by the liver and by the skeletal muscle. These transport changes would enhance the availability of substrates for increased gluconeogenesis during starvation."} {"id": "PMID:1259000", "title": "Colonic absorption of bacterially synthesized vitamin K2 in the rat.", "content": "Colonic absorption of bacterially synthesized vitamin K2 ([3H]menaquinone-9) was studied with everted rat colonic sacs in vitro. The mean +/- SE rate of absorption of the vitamin by the colon was 20 +/- 1.45 pmol/min per 100 mg tissue at 300 nM mucosal concentration of the vitamin. The rate of absorption did not change (P greater than 0.10) with the addition of 2,4-dinitrophenol, Na azide, or KCN to the mucosal incubation medium. No evidence for transmural transport of the vitamin was detectable. When the concentration of the vitamin was increased in a stepwise fashion up to 900 nM, the absorption rate remained linear with respect to the mucosal fluid concentration (r = 0.98). Autoradiography indicated that the vitamin accumulated in the mucosal and submucosal layers of the large bowel. Absorption of the vitamin by the large bowel takes place via a passive, nonsaturable process that shows no evidence of energy dependence or carrier mediation. It was concluded that vitamin K2 (bacterial origin) is absorbable by the rat colon in amounts sufficient to meet the daily requirement of the animal and may explain the lack of bleeding problems in the face of episodic lack of dietary vitamin K.", "contents": "Colonic absorption of bacterially synthesized vitamin K2 in the rat. Colonic absorption of bacterially synthesized vitamin K2 ([3H]menaquinone-9) was studied with everted rat colonic sacs in vitro. The mean +/- SE rate of absorption of the vitamin by the colon was 20 +/- 1.45 pmol/min per 100 mg tissue at 300 nM mucosal concentration of the vitamin. The rate of absorption did not change (P greater than 0.10) with the addition of 2,4-dinitrophenol, Na azide, or KCN to the mucosal incubation medium. No evidence for transmural transport of the vitamin was detectable. When the concentration of the vitamin was increased in a stepwise fashion up to 900 nM, the absorption rate remained linear with respect to the mucosal fluid concentration (r = 0.98). Autoradiography indicated that the vitamin accumulated in the mucosal and submucosal layers of the large bowel. Absorption of the vitamin by the large bowel takes place via a passive, nonsaturable process that shows no evidence of energy dependence or carrier mediation. It was concluded that vitamin K2 (bacterial origin) is absorbable by the rat colon in amounts sufficient to meet the daily requirement of the animal and may explain the lack of bleeding problems in the face of episodic lack of dietary vitamin K."} {"id": "PMID:1259001", "title": "Low Na+ effects on PAH transport and permeabilities in isolated snake renal tubules.", "content": "Effects of low sodium concentrations on p-aminohippurate (PAH) transport by isolated, perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Replacement of sodium in bath with choline led to significant depression of net PAH transport from bath to lumen in less than 10 min and to maximum depression (to 25-30% of control) in about 30 min, but transport still occurred against concentration gradient. In absence of sodium, PAH concentration in cell water was markedly depressed, but was still slightly greater than that in bath or lumen. Apparent permeability of peritubular membrane, determined from PAH efflux from tubules with oil-filled lumens, averaged about 0.5 X 10(-5) cm s-1 in 150 mM sodium and about 1.1 X 10(-5) cm s-1 in sodium-free medium. Data suggest that both decreased rate of active transport and increased apparent permeability of peritubular membrane contribute to depression of net transepithelial PAH transport and cell water PAH concentration in sodium-free medium. When sodium was restored to bath, net PAH transport nearly tripled in 15 min. Reduction of bath sodium concentration to one-half control or perfusion with sodium-free medium in lumen and control medium in bath had no effect on net PAH transport.", "contents": "Low Na+ effects on PAH transport and permeabilities in isolated snake renal tubules. Effects of low sodium concentrations on p-aminohippurate (PAH) transport by isolated, perfused snake (Thamnophis spp.) distal-proximal renal tubules were studied. Replacement of sodium in bath with choline led to significant depression of net PAH transport from bath to lumen in less than 10 min and to maximum depression (to 25-30% of control) in about 30 min, but transport still occurred against concentration gradient. In absence of sodium, PAH concentration in cell water was markedly depressed, but was still slightly greater than that in bath or lumen. Apparent permeability of peritubular membrane, determined from PAH efflux from tubules with oil-filled lumens, averaged about 0.5 X 10(-5) cm s-1 in 150 mM sodium and about 1.1 X 10(-5) cm s-1 in sodium-free medium. Data suggest that both decreased rate of active transport and increased apparent permeability of peritubular membrane contribute to depression of net transepithelial PAH transport and cell water PAH concentration in sodium-free medium. When sodium was restored to bath, net PAH transport nearly tripled in 15 min. Reduction of bath sodium concentration to one-half control or perfusion with sodium-free medium in lumen and control medium in bath had no effect on net PAH transport."} {"id": "PMID:1259002", "title": "Basis for phase relations between baroreceptor and sympathetic nervous discharge.", "content": "The phase relations between the cardiac cycle and sympathetic nervous discharge (SND) were studied with an average-response computer in the anesthetized cat. Maximum SND occurred during early diastole at heart rates between 3 and 4 beats/s. Dramatic shifts in the phase relations between SND and the cardiac cycle accompanied the decrease in heart rate produced by stimulation of the distal end of the cut right vagus nerve. The point of maximum SND was shifted from early diastole to near peak systole and then into the late diastolic phase of the preceding cardiac cycle as heart rate was progressively lowered to 2 beats/s. These observations indicate that synchronization of SND during each cardiac cycle is not the simple consequence of the waxing and waning of baroreceptor nerve activity. Rather, 1:1 locking of bursts of SND to the cardiac cycle is explained on the basis of entrainment by the baroreceptor reflexes of a sympathetic rhythm of central origin. An inhibitory-phasing hypothesis is proposed to account for entrainment. In addition, two components (spinal and brainstem) of sympathoinhibition associated with the pulse-synchronous discharge of the carotid sinus nerve were revealed when the 1:1 relationship between bursts of SND and the cardiac cycle was disrupted at heart rates below 2 beats/s.", "contents": "Basis for phase relations between baroreceptor and sympathetic nervous discharge. The phase relations between the cardiac cycle and sympathetic nervous discharge (SND) were studied with an average-response computer in the anesthetized cat. Maximum SND occurred during early diastole at heart rates between 3 and 4 beats/s. Dramatic shifts in the phase relations between SND and the cardiac cycle accompanied the decrease in heart rate produced by stimulation of the distal end of the cut right vagus nerve. The point of maximum SND was shifted from early diastole to near peak systole and then into the late diastolic phase of the preceding cardiac cycle as heart rate was progressively lowered to 2 beats/s. These observations indicate that synchronization of SND during each cardiac cycle is not the simple consequence of the waxing and waning of baroreceptor nerve activity. Rather, 1:1 locking of bursts of SND to the cardiac cycle is explained on the basis of entrainment by the baroreceptor reflexes of a sympathetic rhythm of central origin. An inhibitory-phasing hypothesis is proposed to account for entrainment. In addition, two components (spinal and brainstem) of sympathoinhibition associated with the pulse-synchronous discharge of the carotid sinus nerve were revealed when the 1:1 relationship between bursts of SND and the cardiac cycle was disrupted at heart rates below 2 beats/s."} {"id": "PMID:1259003", "title": "Reflex effects of thermal stimulation on sympathetic nerve activity to skin and kidney.", "content": "Effects of peripheral and central thermoreceptor reflexes on sympathetic nerve activity to the skin (SkNA) and kidney (RNA) were compared in anesthetized cats. Sudden warming of the skin produced a rapid increase of RNA, wheras sudden cooling produced a rapid increase of SkNA. When the bath temperature (TB) was 17.6, 29.7, and 41.9 degrees C, the normalized SkNA was 100, 82, and 48%, while the normalized RNA was 81, 90, and 100%, respectively. Similarly, under open baroceptor loop conditions, SkNA changed inversely with TB, while RNA changed proportionally to TB. Changes in the temperature of the whole brain including hypothalamus (Thy) modified the amplitude of grouped RNA and SkNA synchronously with the cardiac cycle. At TB of 32.4 degrees C, when Thy was altered in a range of 30-42 degrees C, SkNA reached a maximum level at a Thy of 38.4 degrees C, whereas RNA reached a maximum above 42 degrees C. In a Thy range of 38-42 degrees C, the slopes of the Thy-SkNA curve and Thy-RNA curve were 30 and +4%/degrees C, respectively. At Thy below 38 degrees C, SkNA and RNA changed in parallel with Thy. Continuous cooling of the skin modified the slope of the TB-SkNA curve, but a small change of Thy caused a shift of the TB-SkNA curve.", "contents": "Reflex effects of thermal stimulation on sympathetic nerve activity to skin and kidney. Effects of peripheral and central thermoreceptor reflexes on sympathetic nerve activity to the skin (SkNA) and kidney (RNA) were compared in anesthetized cats. Sudden warming of the skin produced a rapid increase of RNA, wheras sudden cooling produced a rapid increase of SkNA. When the bath temperature (TB) was 17.6, 29.7, and 41.9 degrees C, the normalized SkNA was 100, 82, and 48%, while the normalized RNA was 81, 90, and 100%, respectively. Similarly, under open baroceptor loop conditions, SkNA changed inversely with TB, while RNA changed proportionally to TB. Changes in the temperature of the whole brain including hypothalamus (Thy) modified the amplitude of grouped RNA and SkNA synchronously with the cardiac cycle. At TB of 32.4 degrees C, when Thy was altered in a range of 30-42 degrees C, SkNA reached a maximum level at a Thy of 38.4 degrees C, whereas RNA reached a maximum above 42 degrees C. In a Thy range of 38-42 degrees C, the slopes of the Thy-SkNA curve and Thy-RNA curve were 30 and +4%/degrees C, respectively. At Thy below 38 degrees C, SkNA and RNA changed in parallel with Thy. Continuous cooling of the skin modified the slope of the TB-SkNA curve, but a small change of Thy caused a shift of the TB-SkNA curve."} {"id": "PMID:1259004", "title": "Effects of time on volume and distribution of coronary collateral flow.", "content": "Changes in the volume and distribution of collateral blood flow were studied during the 1st h after coronary occlusion in nine open-chest dogs. Labeled microspheres (7-10 mum) were injected into the left atrium prior to and 20 s, 5 min, and 60 min after acute occlusion of the midcircumflex coronary artery so that myocardial perfusion to small segments of the entire left ventricle could be measured. The segmental perfusions were classified as normally perfused, severely hypoperfused, moderately hypoperfused, and borderline hypoperfused. Standard hemodynamic measurements were obtained and relative coronary vascular resistance to the normally perfused and hypoperfused zones was calculated. The principal conclusions of the study are as follows: 1) during the 1st h after coronary occlusion the collateral flow to the hypoperfused myocardium increases substantially; 2) the increase in collateral flow is distributed fairly evenly to various hypoperfused zones and is associated with a marked decrease in coronary vascular resistance; and 3) as a result of this influx in collateral flow the size of the hypoperfused area decreases and the relative proportion of severely hypoperfused segments within the hypoperfused area decreases.", "contents": "Effects of time on volume and distribution of coronary collateral flow. Changes in the volume and distribution of collateral blood flow were studied during the 1st h after coronary occlusion in nine open-chest dogs. Labeled microspheres (7-10 mum) were injected into the left atrium prior to and 20 s, 5 min, and 60 min after acute occlusion of the midcircumflex coronary artery so that myocardial perfusion to small segments of the entire left ventricle could be measured. The segmental perfusions were classified as normally perfused, severely hypoperfused, moderately hypoperfused, and borderline hypoperfused. Standard hemodynamic measurements were obtained and relative coronary vascular resistance to the normally perfused and hypoperfused zones was calculated. The principal conclusions of the study are as follows: 1) during the 1st h after coronary occlusion the collateral flow to the hypoperfused myocardium increases substantially; 2) the increase in collateral flow is distributed fairly evenly to various hypoperfused zones and is associated with a marked decrease in coronary vascular resistance; and 3) as a result of this influx in collateral flow the size of the hypoperfused area decreases and the relative proportion of severely hypoperfused segments within the hypoperfused area decreases."} {"id": "PMID:1259005", "title": "Response to parathyroid hormone in defined segments of proximal tubule.", "content": "Previous investigations have suggested that there is a functional heterogeneity along the length of the proximal convoluted tubule. This study was designed to confirm and extend these suggestions by examining the intrinsic absorption of fluid and the effect of parathyroid hormone (PTH) on net fluid absorption in isolated, anatomically defined segments of rabbit superficial proximal tubules. The EPCT (early proximal convoluted tubule), LPCT (late proximal convoluted tubule), and PR (pars recta) segments were studied under controlled conditions by the isolated perfused tubule technique. In 23 EPCT, base-line fluid absorption was 1.38 +/- 0.04 (SE), a rate significantly higher than those of 11 LPCT (0.62 +/- 0.02; P less than 0.001) and 12 PR (0.52 +/- 0.03 nl mm-1 min-1, P less than 0.001) segments. In 10 EPCT, mean control fluid absorption was 1.31 +/- 0.04 nl mm-1 min-1; addition of PTH resulted in a decrease to 0.95 +/- 0.05 nl mm-1 min-1 (P less than 0.001); and, after removal of PTH, fluid absorption increased (P less than 0.001). Parathyroid hormone had no effect on either seven LPCT segments or six PR segments. These results demonstrate differences in intrinsic capacity to absorb fluid by anatomically defined segments of the rabbit proximal tubule. This functional heterogeneity is further supported by the observed differential response to PTH by the various anatomic segments of the proximal tubule.", "contents": "Response to parathyroid hormone in defined segments of proximal tubule. Previous investigations have suggested that there is a functional heterogeneity along the length of the proximal convoluted tubule. This study was designed to confirm and extend these suggestions by examining the intrinsic absorption of fluid and the effect of parathyroid hormone (PTH) on net fluid absorption in isolated, anatomically defined segments of rabbit superficial proximal tubules. The EPCT (early proximal convoluted tubule), LPCT (late proximal convoluted tubule), and PR (pars recta) segments were studied under controlled conditions by the isolated perfused tubule technique. In 23 EPCT, base-line fluid absorption was 1.38 +/- 0.04 (SE), a rate significantly higher than those of 11 LPCT (0.62 +/- 0.02; P less than 0.001) and 12 PR (0.52 +/- 0.03 nl mm-1 min-1, P less than 0.001) segments. In 10 EPCT, mean control fluid absorption was 1.31 +/- 0.04 nl mm-1 min-1; addition of PTH resulted in a decrease to 0.95 +/- 0.05 nl mm-1 min-1 (P less than 0.001); and, after removal of PTH, fluid absorption increased (P less than 0.001). Parathyroid hormone had no effect on either seven LPCT segments or six PR segments. These results demonstrate differences in intrinsic capacity to absorb fluid by anatomically defined segments of the rabbit proximal tubule. This functional heterogeneity is further supported by the observed differential response to PTH by the various anatomic segments of the proximal tubule."} {"id": "PMID:1259006", "title": "Influence of fasting on lung oxygen consumption and respiratory quotient.", "content": "We measured the oxygen consumption (QO2) of lung slices from rats and rabbits and the respiratory quotient (RQ) of lung slices from fed and fasted rats. The QO2 of lung slices is lowered within 24 h after the onset of food deprivation; this decrease in QO2 lasts during at least 2 additional days of fasting and is not eliminated by addition of glucose to the reaction medium. In fed rats the RQ of lung slices after 30 min of incubation without glucose is 0.75 +/- 0.01 (mean +/- SE) and 0.96 +/- 0.02 with glucose present. Fasting for 72 h lowers the RQ of lung slices after 30 min of incubation without glucose to 0.68 +/- 0.03; addition of glucose raises the RQ of lung slices from 72-h-fasted rats to 0.76 +/- 0.02. We conclude that fasting depresses lung oxidative metabolism. In the fed rat glucose is a major substrate for oxidative processes but in the fasting rat the oxidation of glucose is impaired and lipids are an important source of lung energy.", "contents": "Influence of fasting on lung oxygen consumption and respiratory quotient. We measured the oxygen consumption (QO2) of lung slices from rats and rabbits and the respiratory quotient (RQ) of lung slices from fed and fasted rats. The QO2 of lung slices is lowered within 24 h after the onset of food deprivation; this decrease in QO2 lasts during at least 2 additional days of fasting and is not eliminated by addition of glucose to the reaction medium. In fed rats the RQ of lung slices after 30 min of incubation without glucose is 0.75 +/- 0.01 (mean +/- SE) and 0.96 +/- 0.02 with glucose present. Fasting for 72 h lowers the RQ of lung slices after 30 min of incubation without glucose to 0.68 +/- 0.03; addition of glucose raises the RQ of lung slices from 72-h-fasted rats to 0.76 +/- 0.02. We conclude that fasting depresses lung oxidative metabolism. In the fed rat glucose is a major substrate for oxidative processes but in the fasting rat the oxidation of glucose is impaired and lipids are an important source of lung energy."} {"id": "PMID:1259007", "title": "Influence of thyroxine on adult rat lung oxygen consumption and ultrastructure.", "content": "We studied the oxygen consumption (QO2) of lung slices and the ultrastructure of the pulmonary granular pneumocyte in rats whose level of circulating thyroxine was altered. Rats given thyroxine for 6 days (1.0 mg-kg-1-day-1) and sacrificed on the 7th day had a serum thyroxine level of 18.9 +/- 2.7 mug/100 ml (mean +/- SD); rats given diluent alone for 6 days had a serum thyroxine level of 4.67 +/- 0.53 mug/100 ml. Rats subjected to a sham thyroidectomy has a serum thyroxine level of 7.27 +/- 1.47 mug/100 ml, whereas rats subjected to thyroidectomy had a serum thyroxine level of 1.13 +/- 0.55 mug/100 ml when sacrificed. The QO2 of lung slices from rats with high levels of circulating thyroxine was significantly greater than that of rats that received diluent alone. The QO2 of slices from rats whose thyroid glands were excised was significantly lower than the QO2 of slices from sham-operated rats. We did not find quantitative ultrastructural differences in granular pneumocyte mitochondria and lamellar bodies of rats given thyroxine compared to rats given diluent or between rats subjected to sham thyroidectomy compared to rats whose thyroid glands were removed.", "contents": "Influence of thyroxine on adult rat lung oxygen consumption and ultrastructure. We studied the oxygen consumption (QO2) of lung slices and the ultrastructure of the pulmonary granular pneumocyte in rats whose level of circulating thyroxine was altered. Rats given thyroxine for 6 days (1.0 mg-kg-1-day-1) and sacrificed on the 7th day had a serum thyroxine level of 18.9 +/- 2.7 mug/100 ml (mean +/- SD); rats given diluent alone for 6 days had a serum thyroxine level of 4.67 +/- 0.53 mug/100 ml. Rats subjected to a sham thyroidectomy has a serum thyroxine level of 7.27 +/- 1.47 mug/100 ml, whereas rats subjected to thyroidectomy had a serum thyroxine level of 1.13 +/- 0.55 mug/100 ml when sacrificed. The QO2 of lung slices from rats with high levels of circulating thyroxine was significantly greater than that of rats that received diluent alone. The QO2 of slices from rats whose thyroid glands were excised was significantly lower than the QO2 of slices from sham-operated rats. We did not find quantitative ultrastructural differences in granular pneumocyte mitochondria and lamellar bodies of rats given thyroxine compared to rats given diluent or between rats subjected to sham thyroidectomy compared to rats whose thyroid glands were removed."} {"id": "PMID:1259008", "title": "Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction.", "content": "To delineate the mechanism through which vasoactive compounds alter intestinal oxygen consumption and to determine the pharmacological nature of the receptors involved, we quantitated the effects of vasoconstrictors on arteriovenous oxygen difference and on vascular resistance in isolated constant-flow perfused canine small bowel. Norepinephrine (NE) and sympathetic stimulation (SS) increased vascular resistance and depressed O2 extraction. These effects were not altered by beta-blockade, but were abolished by alpha-blockade. Since capillary filtration coefficients at constant-pressure perfusion and 86Rb extraction at constant flow are reported to diminish during NE and SS, it follows that these agents reduce O2 extraction by an alpha-adrenergic closure of precapillary sphincters. Vasopressin had similar effects which were not affected by adrenergic blocking agents. Epinephrine (Epi) in high doses or after propranolol produced the same effects as NE and SS. By contrast, Epi in low doses increased O2 and 86Rb extraction. This response to low doses of Epi was not affected by phentolamine, but was reversed by propranolol. We conclude that Epi in high doses or after propranolol depresses intestinal O2 extraction by the same mechanism as NE and SS, but the mechanism through which Epi increases intestinal O2 extraction is unclear.", "contents": "Effects of vasoconstrictors on intestinal vascular resistance and oxygen extraction. To delineate the mechanism through which vasoactive compounds alter intestinal oxygen consumption and to determine the pharmacological nature of the receptors involved, we quantitated the effects of vasoconstrictors on arteriovenous oxygen difference and on vascular resistance in isolated constant-flow perfused canine small bowel. Norepinephrine (NE) and sympathetic stimulation (SS) increased vascular resistance and depressed O2 extraction. These effects were not altered by beta-blockade, but were abolished by alpha-blockade. Since capillary filtration coefficients at constant-pressure perfusion and 86Rb extraction at constant flow are reported to diminish during NE and SS, it follows that these agents reduce O2 extraction by an alpha-adrenergic closure of precapillary sphincters. Vasopressin had similar effects which were not affected by adrenergic blocking agents. Epinephrine (Epi) in high doses or after propranolol produced the same effects as NE and SS. By contrast, Epi in low doses increased O2 and 86Rb extraction. This response to low doses of Epi was not affected by phentolamine, but was reversed by propranolol. We conclude that Epi in high doses or after propranolol depresses intestinal O2 extraction by the same mechanism as NE and SS, but the mechanism through which Epi increases intestinal O2 extraction is unclear."} {"id": "PMID:1259009", "title": "Renin-angiotensin-aldosterone system in experimental renal hypertension in the rabbit.", "content": "Hypertension was produced in 25 rabbits by constricting the right renal artery and leaving the opposite kidney intact (two-kidney hypertension). After 30 days mean arterial pressure and plasma renin activity (PRA) were significantly elevated (P less than 0.01), and arterial pressure was correlated with PRA (r = 0.551, P less than 0.01); however, not all hypertensive rabbits had elevated PRA, and in animals in which sodium balance was monitored, only rabbits in negative sodium balance had increased levels of PRA. To investigate the role of angiotensin II (A-II) in the hypertension, [1-sarcosine,8-alanine]angiotensin II was infused at 6 mug/kg per min for 30 min in anesthetized hypertensive animals (n = 25). For the group, arterial pressure fell significantly (P less than 0.01), but several animals with minimal hypertension failed to give a depressor response. The declines in arterial pressure were highly correlated with PRA (r = 0.853, P less than 0.01). Aldosterone secretion in hypertensive animals was correlated with PRA (r = 0.851, P less than 0.01). Thus, two-kidney hypertension in the rabbit persists with normal PRA, but during periods of spontaneous sodium depletion, A-II plays a role in the maintenance of the hypertension.", "contents": "Renin-angiotensin-aldosterone system in experimental renal hypertension in the rabbit. Hypertension was produced in 25 rabbits by constricting the right renal artery and leaving the opposite kidney intact (two-kidney hypertension). After 30 days mean arterial pressure and plasma renin activity (PRA) were significantly elevated (P less than 0.01), and arterial pressure was correlated with PRA (r = 0.551, P less than 0.01); however, not all hypertensive rabbits had elevated PRA, and in animals in which sodium balance was monitored, only rabbits in negative sodium balance had increased levels of PRA. To investigate the role of angiotensin II (A-II) in the hypertension, [1-sarcosine,8-alanine]angiotensin II was infused at 6 mug/kg per min for 30 min in anesthetized hypertensive animals (n = 25). For the group, arterial pressure fell significantly (P less than 0.01), but several animals with minimal hypertension failed to give a depressor response. The declines in arterial pressure were highly correlated with PRA (r = 0.853, P less than 0.01). Aldosterone secretion in hypertensive animals was correlated with PRA (r = 0.851, P less than 0.01). Thus, two-kidney hypertension in the rabbit persists with normal PRA, but during periods of spontaneous sodium depletion, A-II plays a role in the maintenance of the hypertension."} {"id": "PMID:1259010", "title": "Effects of altering O2 delivery on VO2 of isolated, working muscle.", "content": "Maximal oxygen consumption (VO2 max) and muscle blood flow (Q max) were measured in an isolated gracilis muscle preparation before and after alteration in perfusion pressure (BP), arterial oxygen saturation (SaO2), and hemoglobin concentration (Hb). Q varied directly with BP and inversely with Hb (viscosity) but was unaffected by changes in arterial SaO2. VO2 max varied directly with oxygen delivery under all conditions. These results indicate that VO2 max is normally limited by oxygen delivery rather than any intrinsic limiting of oxygen consumption of the muscle.", "contents": "Effects of altering O2 delivery on VO2 of isolated, working muscle. Maximal oxygen consumption (VO2 max) and muscle blood flow (Q max) were measured in an isolated gracilis muscle preparation before and after alteration in perfusion pressure (BP), arterial oxygen saturation (SaO2), and hemoglobin concentration (Hb). Q varied directly with BP and inversely with Hb (viscosity) but was unaffected by changes in arterial SaO2. VO2 max varied directly with oxygen delivery under all conditions. These results indicate that VO2 max is normally limited by oxygen delivery rather than any intrinsic limiting of oxygen consumption of the muscle."} {"id": "PMID:1259011", "title": "Sympathetic control of Na, K transport in perfused submaxillary main duct of rat.", "content": "The effect of stimulating the sympathetic innervation to rat submaxillary gland on ductal transport of Na, K, and water and on transepithelial PD was tested in the main excretory duct during perfusion through its lumen. Stimulation of the sympathetic nerve, supramaximally, caused a decrease of 30-40% in net flux of Na from, and of K to, the lumen in ducts perfused with medium containing Na and K in isotonic concentrations. Net flux of water was unaffected. Transductal PD decreased by about 30% during supramaximal stimulation. Changes in PD and net cation fluxes were reversible. These effects of supramaximal stimulation of the sympathetics on ductal transport resemble those reported to occur after large doses of isoproterenol and suggest an adrenergic secretomotor innervation to the ducts. However, changes in PD evoked by supramaximal stimulation of the sympathetic nerve could not be suppressed with propranolol, but were with phenoxybenzamine, indicating that alpha-adrenergic receptors are primarily involved in mediating at least the electrical responses of duct cells to sympathetic nerve stimulation.", "contents": "Sympathetic control of Na, K transport in perfused submaxillary main duct of rat. The effect of stimulating the sympathetic innervation to rat submaxillary gland on ductal transport of Na, K, and water and on transepithelial PD was tested in the main excretory duct during perfusion through its lumen. Stimulation of the sympathetic nerve, supramaximally, caused a decrease of 30-40% in net flux of Na from, and of K to, the lumen in ducts perfused with medium containing Na and K in isotonic concentrations. Net flux of water was unaffected. Transductal PD decreased by about 30% during supramaximal stimulation. Changes in PD and net cation fluxes were reversible. These effects of supramaximal stimulation of the sympathetics on ductal transport resemble those reported to occur after large doses of isoproterenol and suggest an adrenergic secretomotor innervation to the ducts. However, changes in PD evoked by supramaximal stimulation of the sympathetic nerve could not be suppressed with propranolol, but were with phenoxybenzamine, indicating that alpha-adrenergic receptors are primarily involved in mediating at least the electrical responses of duct cells to sympathetic nerve stimulation."} {"id": "PMID:1259012", "title": "Primate gastric circulation: effects of catecholamines and adrenergic blockade.", "content": "The effects of intra-arterial injections and infusions of epinephrine, norepinephrine, and isoproterenol on gastric blood flow were studied in anesthetized baboons. Blood flow was measured electromagnetically before and after adrenergic blockade. The results for injected epinephrine and norepinephrine indicate these agents to be pure vasoconstrictors in the primate gastric circulation, and this response is attenuated by alpha-adrenergic blockade with phenoxybenzamine. Isoproterenol is a pure vasodilator, and its response is attenuated following beta-adrenergic blockade with propranolol. Intra-arterial infusions of epinephrine and norepinephrine (.05 mug kg-1 min-1) resulted in sustained vasoconstriction with no evidence of autoregulatory escape and no postinfusion \"over-shoot.\" This study suggests that epinephrine and norepinephrine might provide alternatives to vasopressin as a vasoconstrictor for the control of upper gastrointestinal bleeding.", "contents": "Primate gastric circulation: effects of catecholamines and adrenergic blockade. The effects of intra-arterial injections and infusions of epinephrine, norepinephrine, and isoproterenol on gastric blood flow were studied in anesthetized baboons. Blood flow was measured electromagnetically before and after adrenergic blockade. The results for injected epinephrine and norepinephrine indicate these agents to be pure vasoconstrictors in the primate gastric circulation, and this response is attenuated by alpha-adrenergic blockade with phenoxybenzamine. Isoproterenol is a pure vasodilator, and its response is attenuated following beta-adrenergic blockade with propranolol. Intra-arterial infusions of epinephrine and norepinephrine (.05 mug kg-1 min-1) resulted in sustained vasoconstriction with no evidence of autoregulatory escape and no postinfusion \"over-shoot.\" This study suggests that epinephrine and norepinephrine might provide alternatives to vasopressin as a vasoconstrictor for the control of upper gastrointestinal bleeding."} {"id": "PMID:1259013", "title": "Acetate as a metabolic substrate in the fetal lamb.", "content": "Fetal acetate metabolsim was studied in chronically catheterized fetal lambs of 110-141 days' gestation. Acetate concentration was measured enzymatically in whole blood drawn simultaneously from maternal and fetal pre- and postplacental vessels. The oxygen content of the fetal blood samples was also measured. Fetal umbilical venous acetate concentration was found to be proportional to the maternal arterial acetate concentration and had a mean value of 0.366 mM. Fetal blood acetate increased significantly, by a mean of 0.081 mM, during circulation through the placenta. This increase was proportional to both the maternal acetate concentration and the concentration gradient of acetate across the placenta. The mean maternal arterial acetate concentration was 1.153 mM. Maternal blood lost significant amounts of acetate, 0.112 mM, during circulation through the uterus and appeared to be the source of the acetate being gained by the fetus. It is estimated that a total of 23 mmol of acetate/kg of fetal weight is being taken up by the fetus each day, providing it with 0.560 g of carbon/kg. Comparisons of acetate uptake with fetal oxygen uptake indicate 10% of the daily fetal oxygen consumption would be required to completely oxidize the acetate being gained by the fetus.", "contents": "Acetate as a metabolic substrate in the fetal lamb. Fetal acetate metabolsim was studied in chronically catheterized fetal lambs of 110-141 days' gestation. Acetate concentration was measured enzymatically in whole blood drawn simultaneously from maternal and fetal pre- and postplacental vessels. The oxygen content of the fetal blood samples was also measured. Fetal umbilical venous acetate concentration was found to be proportional to the maternal arterial acetate concentration and had a mean value of 0.366 mM. Fetal blood acetate increased significantly, by a mean of 0.081 mM, during circulation through the placenta. This increase was proportional to both the maternal acetate concentration and the concentration gradient of acetate across the placenta. The mean maternal arterial acetate concentration was 1.153 mM. Maternal blood lost significant amounts of acetate, 0.112 mM, during circulation through the uterus and appeared to be the source of the acetate being gained by the fetus. It is estimated that a total of 23 mmol of acetate/kg of fetal weight is being taken up by the fetus each day, providing it with 0.560 g of carbon/kg. Comparisons of acetate uptake with fetal oxygen uptake indicate 10% of the daily fetal oxygen consumption would be required to completely oxidize the acetate being gained by the fetus."} {"id": "PMID:1259014", "title": "Effects of age and fasting on gluconeogenesis from glycerol in dogs.", "content": "The extent of gluconeogenesis from glycerol was examined in pups and adult dogs. With use of the SAAM-26 program, a four compartment model was formulated from tracer data to calculate the kinetics of the glycerol:glucose system. In the postabsorptive state gluconeogenesis from glycerol declines with age: 13.8% of glucose carbon originated from glycerol in 0- to 4-day-old pups, 6% in adults. Approximately 50% of glycerol carbon is converted to glucose carbon independent of age. During fasting, a) the percentage of glucose carbon arising from glycerol carbon increased to 13.3% and 10.3% in adult dogs and pups 5-19 days old, respectively, in younger pups it declined to 3.4%; b) glycerol production increased in adults, but decreased in the youngest pups; c) glucose production and utilization decreased at all ages, and a smaller percentage of glycerol carbon was converted to glucose carbon, especially in the youngest pups. Thus in neonates fasting decreases gluconeogenesis from glycerol.", "contents": "Effects of age and fasting on gluconeogenesis from glycerol in dogs. The extent of gluconeogenesis from glycerol was examined in pups and adult dogs. With use of the SAAM-26 program, a four compartment model was formulated from tracer data to calculate the kinetics of the glycerol:glucose system. In the postabsorptive state gluconeogenesis from glycerol declines with age: 13.8% of glucose carbon originated from glycerol in 0- to 4-day-old pups, 6% in adults. Approximately 50% of glycerol carbon is converted to glucose carbon independent of age. During fasting, a) the percentage of glucose carbon arising from glycerol carbon increased to 13.3% and 10.3% in adult dogs and pups 5-19 days old, respectively, in younger pups it declined to 3.4%; b) glycerol production increased in adults, but decreased in the youngest pups; c) glucose production and utilization decreased at all ages, and a smaller percentage of glycerol carbon was converted to glucose carbon, especially in the youngest pups. Thus in neonates fasting decreases gluconeogenesis from glycerol."} {"id": "PMID:1259015", "title": "Characterization of midbrain component of the trigger for arousal from hibernation.", "content": "The ability of the midbrain reticular formation (MRF) to trigger arousal from hibernation and to change body temperature (Tb) during euthermia was tested in golden-mantled ground squirrels (Citellus lateralis). During hibernation (ambient temperature 5-6 degrees C) microinjections of cholinomimetic compounds (acetylcholine and carbachol) triggered full arousal or produced transient increases in Tb in 15 out of 19 tests; MRF microinjections of norepinephrine (NE) and 5-hydroxytryptamine (5-HT), at the same concentrations that produced full arousal when microinjected into the preoptic/anterior hypothalamus (PO/AH) area in previous experiments, has no effect on Tb in 13 out of 16 tests. In experiments on euthermic ground squirrels tested at an ambient temperature of 25 degrees C, MRF microinjections of acetylcholine raised Tb, whereas the monoamines had no significant effects. These results show that cholinoceptive neurons in the MRF can trigger arousal from hibernation and increase Tb during euthermia. The failure of NE and 5-HT to produce any significant effects at the same doses that were reported to be effective in the PO/AH indicates that the functional organization of the MRF portion of the arousal mechanism is different from that reported for the PO/AH.", "contents": "Characterization of midbrain component of the trigger for arousal from hibernation. The ability of the midbrain reticular formation (MRF) to trigger arousal from hibernation and to change body temperature (Tb) during euthermia was tested in golden-mantled ground squirrels (Citellus lateralis). During hibernation (ambient temperature 5-6 degrees C) microinjections of cholinomimetic compounds (acetylcholine and carbachol) triggered full arousal or produced transient increases in Tb in 15 out of 19 tests; MRF microinjections of norepinephrine (NE) and 5-hydroxytryptamine (5-HT), at the same concentrations that produced full arousal when microinjected into the preoptic/anterior hypothalamus (PO/AH) area in previous experiments, has no effect on Tb in 13 out of 16 tests. In experiments on euthermic ground squirrels tested at an ambient temperature of 25 degrees C, MRF microinjections of acetylcholine raised Tb, whereas the monoamines had no significant effects. These results show that cholinoceptive neurons in the MRF can trigger arousal from hibernation and increase Tb during euthermia. The failure of NE and 5-HT to produce any significant effects at the same doses that were reported to be effective in the PO/AH indicates that the functional organization of the MRF portion of the arousal mechanism is different from that reported for the PO/AH."} {"id": "PMID:1259016", "title": "Protein composition of lung fluids in acute alloxan edema in dogs.", "content": "In 11 anesthetized dogs with acute alloxan-induced pulmonary edema, we measured the protein composition of 1-mul samples of plasma, free interstitial fluid, alveolar fluid, and airway fluid. We obtained plasma and airway fluid at regular intervals as edema developed. We sampled alveolar fluid by pleural micropuncture in the unfrozen, excised lung and free interstitial fluid from perivascular cuffs in the frozen, excised lung. The average (+/- 1 SD) total protein concentration of plasma was 4.9 +/- 0.6, airway fluid 4.4 +/- 0.7, free interstitial fluid 4.9 +/- 0.7, and alveolar fluid 5.2 +/- 0.8 g/100 ml. The average fractions of albumin were 0.42 +/- 0.05, 0.50 +/- 0.05, 0.49 +/- 0.06, and 0.49 +/- 0.07, respectively. By paired analysis, the protein concentration of interstitial fluid was not significantly different from alveolar fluid. The protein concentration of airway fluid was significantly less than that in interstitial and alveolar fluid. The albumin fraction of the three lung fluids was identical but significantly different from plasma. We conclude that in alloxan-induced pulmonary edema the lung fluids contain high concentrations of protein and the alveolar epithelial membrane becomes freely permeable to protein molecules.", "contents": "Protein composition of lung fluids in acute alloxan edema in dogs. In 11 anesthetized dogs with acute alloxan-induced pulmonary edema, we measured the protein composition of 1-mul samples of plasma, free interstitial fluid, alveolar fluid, and airway fluid. We obtained plasma and airway fluid at regular intervals as edema developed. We sampled alveolar fluid by pleural micropuncture in the unfrozen, excised lung and free interstitial fluid from perivascular cuffs in the frozen, excised lung. The average (+/- 1 SD) total protein concentration of plasma was 4.9 +/- 0.6, airway fluid 4.4 +/- 0.7, free interstitial fluid 4.9 +/- 0.7, and alveolar fluid 5.2 +/- 0.8 g/100 ml. The average fractions of albumin were 0.42 +/- 0.05, 0.50 +/- 0.05, 0.49 +/- 0.06, and 0.49 +/- 0.07, respectively. By paired analysis, the protein concentration of interstitial fluid was not significantly different from alveolar fluid. The protein concentration of airway fluid was significantly less than that in interstitial and alveolar fluid. The albumin fraction of the three lung fluids was identical but significantly different from plasma. We conclude that in alloxan-induced pulmonary edema the lung fluids contain high concentrations of protein and the alveolar epithelial membrane becomes freely permeable to protein molecules."} {"id": "PMID:1259017", "title": "Modification of in vivo lacrimal gland secretion by 2,4-dinitrophenol.", "content": "Mecholyl-stimulated flow from the excretory duct of the rabbit lacrimal gland in vivo was recorded continuously and samples of Mecholyl-stimulated fluid were collected before, during, and after 30 min of local intra-arterial infusion of 2,4-dinitrophenol (DNP). Compared with the control period, Mecholyl-stimulated flow during the DNP infusion was 60-70% less; [K+] was the same and [Na+] and [Cl-] were higher in the Mecholyl-stimulated fluid. The changes that occurred during the DNP infusion were not produced by infusion of the solvent (NaHCO3) or an acid with similar pK (para-aminohippuric acid) nor were the changes related to any effect of DNP on the general circulation. The magnitude of the changes during the DNP infusion increased as the dose of DNP increased and the inhibition of flow changes in [Na+] and [Cl-] during the DNP infusion were reversible. The results are compatible with the hypothesis that stimulation by Mecholyl involves oxidative metabolsim at the duct level but they do not exclude the possibility that oxidative metabolism may also be involved in formation of the primary fluid at the acinar level.", "contents": "Modification of in vivo lacrimal gland secretion by 2,4-dinitrophenol. Mecholyl-stimulated flow from the excretory duct of the rabbit lacrimal gland in vivo was recorded continuously and samples of Mecholyl-stimulated fluid were collected before, during, and after 30 min of local intra-arterial infusion of 2,4-dinitrophenol (DNP). Compared with the control period, Mecholyl-stimulated flow during the DNP infusion was 60-70% less; [K+] was the same and [Na+] and [Cl-] were higher in the Mecholyl-stimulated fluid. The changes that occurred during the DNP infusion were not produced by infusion of the solvent (NaHCO3) or an acid with similar pK (para-aminohippuric acid) nor were the changes related to any effect of DNP on the general circulation. The magnitude of the changes during the DNP infusion increased as the dose of DNP increased and the inhibition of flow changes in [Na+] and [Cl-] during the DNP infusion were reversible. The results are compatible with the hypothesis that stimulation by Mecholyl involves oxidative metabolsim at the duct level but they do not exclude the possibility that oxidative metabolism may also be involved in formation of the primary fluid at the acinar level."} {"id": "PMID:1259018", "title": "Effect of exercise on hormone-sensitive lipase activity in rat adipocytes.", "content": "Hormone-sensitive lipase activity was measured in adipocytes of rats subjected to a 12-wk program of treadmill running. Enzyme activity in the runners sacrificed immediately after exercise increased 2.5-fold (P less than 0.001) in tissue exposed to epinephrine and threefold (P less than 0.001) in tissue not exposed to epinephrine, when the results were expressed per gram of adipose tissue. Increases of almost the same magnitude were observed in runners sacrificed 24 h after their last bout of work. These significant increases in enzyme activity, however, were the result of a significant reduction in the size of cells in the epididymal fat pads of the exercisers compared with those of the freely eating sedentary animals (68.7 +/- 2.7 mum vs. 82.0 +/- 2.7 mum; P less than 0.01). When the results were expressed on a per-cell basis, therefore, hormone-sensitive lipase activity, assayed in the presence or absence of epinephrine, was unaffected by the exercise program. These results provide evidence that the lipolytic capacity of adipocytes of normal, untrained rats is sufficiently large to meet the increased demand for free fatty acids imposed by the exercise program without the need for an adaptive increase in enzyme activity.", "contents": "Effect of exercise on hormone-sensitive lipase activity in rat adipocytes. Hormone-sensitive lipase activity was measured in adipocytes of rats subjected to a 12-wk program of treadmill running. Enzyme activity in the runners sacrificed immediately after exercise increased 2.5-fold (P less than 0.001) in tissue exposed to epinephrine and threefold (P less than 0.001) in tissue not exposed to epinephrine, when the results were expressed per gram of adipose tissue. Increases of almost the same magnitude were observed in runners sacrificed 24 h after their last bout of work. These significant increases in enzyme activity, however, were the result of a significant reduction in the size of cells in the epididymal fat pads of the exercisers compared with those of the freely eating sedentary animals (68.7 +/- 2.7 mum vs. 82.0 +/- 2.7 mum; P less than 0.01). When the results were expressed on a per-cell basis, therefore, hormone-sensitive lipase activity, assayed in the presence or absence of epinephrine, was unaffected by the exercise program. These results provide evidence that the lipolytic capacity of adipocytes of normal, untrained rats is sufficiently large to meet the increased demand for free fatty acids imposed by the exercise program without the need for an adaptive increase in enzyme activity."} {"id": "PMID:1259019", "title": "Gastroduodenal motor gradients in the dog after pyloroplasty.", "content": "Circular muscle contractile activity of the antrum and duodenum and gastric emptying of a liquid test meal were investigated in unanesthetized dogs in which the gastroduodenal junction (GDJ) was altered (Heineke-Mikulicz pyloroplasty). After pyloroplasty, antralization (antral-like contractions occurring in the first portion of the duodenum) was observed during the digestive state. Antralization replaced the normal periods of inhibition that separate periods of duodenal contractions during the interdigestive burst. Bethanechol (0.1 mg/kg sc) and metoclopramide (2.0 mg/kg iv) were capable of stimulating interdigestive contractile activity in the altered GDJ. Pentagastrin (1.0 mug/min iv) produced a differential stimulation on the antrum without appreciably affecting duodenal contractile activity. Pyloroplasty also enhanced the emptying of a 300-ml citrate-fat liquid test meal. An intact hypomuscular segment between the antrum and duodenum is important for normal coordinated contractile activity between the antrum and the duodenum and for the normal gastric emptying of liquids.", "contents": "Gastroduodenal motor gradients in the dog after pyloroplasty. Circular muscle contractile activity of the antrum and duodenum and gastric emptying of a liquid test meal were investigated in unanesthetized dogs in which the gastroduodenal junction (GDJ) was altered (Heineke-Mikulicz pyloroplasty). After pyloroplasty, antralization (antral-like contractions occurring in the first portion of the duodenum) was observed during the digestive state. Antralization replaced the normal periods of inhibition that separate periods of duodenal contractions during the interdigestive burst. Bethanechol (0.1 mg/kg sc) and metoclopramide (2.0 mg/kg iv) were capable of stimulating interdigestive contractile activity in the altered GDJ. Pentagastrin (1.0 mug/min iv) produced a differential stimulation on the antrum without appreciably affecting duodenal contractile activity. Pyloroplasty also enhanced the emptying of a 300-ml citrate-fat liquid test meal. An intact hypomuscular segment between the antrum and duodenum is important for normal coordinated contractile activity between the antrum and the duodenum and for the normal gastric emptying of liquids."} {"id": "PMID:1259020", "title": "Effect of magnesium on rat nephron sodium reabsorption: a segmental analysis.", "content": "To evaluate the effect of hypermagnesemia on distal nephron sodium reabsorption, renal clearance, micropuncture, microinjection, and electrophysiological studies were performed in the anesthetized rat before and after intravenous administration of MgCl2, MgSO4, and Na2SO4. Along the proximal tubule, MgCl2 caused a 21% decrease and MgSO4 a 17% decrease in fractional sodium reabsorption, while only a 4% decrease was observed with Na2SO4. In the loop segment, the decrease in fractional sodium reabsorption was 7% with MgCl2, 15% with MgSO4, and 12% with Na2SO4. In the distal tubule and collecting duct, MgCl2 and MgSO4 had no effect on fractional sodium reabsorption, whereas Na2SO4 significntaly depressed sodium reabsorption to a greater extent in the collecting duct than in the distal tubule. Microinjection studies, however, showed that both MgSO4 and Na2SO4 depressed lumen-to-plasma sodium movement across the collecting duct. Early and late distal tubular transepithelial potential difference was unaffected by MgCl2, whereas it was increased by both MgSO4 and Na2SO4. The decrease in sodium reabsorption along the distal tubule and collecting duct produced by Na2SO4 and probably MgSO4 may relate to the increased transepithelial electrochemical gradient for sodium transport produced by the poorly reabsorbable sulfate anion.", "contents": "Effect of magnesium on rat nephron sodium reabsorption: a segmental analysis. To evaluate the effect of hypermagnesemia on distal nephron sodium reabsorption, renal clearance, micropuncture, microinjection, and electrophysiological studies were performed in the anesthetized rat before and after intravenous administration of MgCl2, MgSO4, and Na2SO4. Along the proximal tubule, MgCl2 caused a 21% decrease and MgSO4 a 17% decrease in fractional sodium reabsorption, while only a 4% decrease was observed with Na2SO4. In the loop segment, the decrease in fractional sodium reabsorption was 7% with MgCl2, 15% with MgSO4, and 12% with Na2SO4. In the distal tubule and collecting duct, MgCl2 and MgSO4 had no effect on fractional sodium reabsorption, whereas Na2SO4 significntaly depressed sodium reabsorption to a greater extent in the collecting duct than in the distal tubule. Microinjection studies, however, showed that both MgSO4 and Na2SO4 depressed lumen-to-plasma sodium movement across the collecting duct. Early and late distal tubular transepithelial potential difference was unaffected by MgCl2, whereas it was increased by both MgSO4 and Na2SO4. The decrease in sodium reabsorption along the distal tubule and collecting duct produced by Na2SO4 and probably MgSO4 may relate to the increased transepithelial electrochemical gradient for sodium transport produced by the poorly reabsorbable sulfate anion."} {"id": "PMID:1259021", "title": "Effects of temperature on cardiac transmembrane potentials in hibernation.", "content": "Resting and action potential parameters were measured from papillary muscle isolated from hibernating and control hamsters and from rats. The temperature range of the study was 12-38 degrees C. The decrease in resting membrane potential (Em) with decreasing temperature was significantly less in the hibernation preparations (HH), down to 20 degrees C, than in either the control hamsters or rats. Below 20 degrees C the declines in Em of all preparations were indistinguishable. Action potential magnitude was adequately maintained in HH to 12 degrees C while both control hamster and rat action potentials declined markedly as temperatures were reduced. Both types of hamster preparations showed greatly prolonged action potentials with reduced temperatures as contrasted to a limited prolongation of rat action potentials. The data are suggestive of a membrane modication in hibernation.", "contents": "Effects of temperature on cardiac transmembrane potentials in hibernation. Resting and action potential parameters were measured from papillary muscle isolated from hibernating and control hamsters and from rats. The temperature range of the study was 12-38 degrees C. The decrease in resting membrane potential (Em) with decreasing temperature was significantly less in the hibernation preparations (HH), down to 20 degrees C, than in either the control hamsters or rats. Below 20 degrees C the declines in Em of all preparations were indistinguishable. Action potential magnitude was adequately maintained in HH to 12 degrees C while both control hamster and rat action potentials declined markedly as temperatures were reduced. Both types of hamster preparations showed greatly prolonged action potentials with reduced temperatures as contrasted to a limited prolongation of rat action potentials. The data are suggestive of a membrane modication in hibernation."} {"id": "PMID:1259022", "title": "Evidence for an intrarenal beta receptor in control of renin release.", "content": "Infusion of isoproterenol intravenously in normal dogs at rates of 0.10 or 0.018 mug/min per kg body wt increased renin secretion; at the lower infusion rate arterial pressure (AP) and renal blood flow (RBF) were unchanged. Isoproterenol was also infused into the renal artery in normal dogs at 0.10 mug/min per kg; renin secretion increased in association with an increase in RBF but AP was unchanged. Plasma K concentration was consistently decreased in all three of the above experiments and because hypokalemia is known to increase renin release isoproterenol was not infused intrarenally at the lower rate; the decrease in plasma K level precluded relating the entire response in renin release to isoproterenol. Intrarenal infusion of propranolol at 0.05 mg/kg per h in Na-depleted dogs decreased renin secretion whereas intravenous infusion at the same dose failed to alter renin release. Intrarenal infusion of propranolol at this rate in Na-depleted dogs with a denervated, nonfiltering kidney also decreased renin release. In contrast, intrarenal infusion of phentolamine or phenoxybenzamine in normal dogs failed to alter renin secretion in doses that blocked alpha-adrenergic receptors. These experiments provide strong evidence for an intrarenal beta-adrenergic receptor that mediates renin release, and it seems likely from the experiment in the denervated, nonfiltering kidney that the receptor is located in the juxtaglomerular cells.", "contents": "Evidence for an intrarenal beta receptor in control of renin release. Infusion of isoproterenol intravenously in normal dogs at rates of 0.10 or 0.018 mug/min per kg body wt increased renin secretion; at the lower infusion rate arterial pressure (AP) and renal blood flow (RBF) were unchanged. Isoproterenol was also infused into the renal artery in normal dogs at 0.10 mug/min per kg; renin secretion increased in association with an increase in RBF but AP was unchanged. Plasma K concentration was consistently decreased in all three of the above experiments and because hypokalemia is known to increase renin release isoproterenol was not infused intrarenally at the lower rate; the decrease in plasma K level precluded relating the entire response in renin release to isoproterenol. Intrarenal infusion of propranolol at 0.05 mg/kg per h in Na-depleted dogs decreased renin secretion whereas intravenous infusion at the same dose failed to alter renin release. Intrarenal infusion of propranolol at this rate in Na-depleted dogs with a denervated, nonfiltering kidney also decreased renin release. In contrast, intrarenal infusion of phentolamine or phenoxybenzamine in normal dogs failed to alter renin secretion in doses that blocked alpha-adrenergic receptors. These experiments provide strong evidence for an intrarenal beta-adrenergic receptor that mediates renin release, and it seems likely from the experiment in the denervated, nonfiltering kidney that the receptor is located in the juxtaglomerular cells."} {"id": "PMID:1259023", "title": "Factors influencing left ventricular shortening in isolated canine heart.", "content": "To assess in the intact ventricle the steady-state influence of several mechanical variables on the extent of left ventricular midwall circumferential shortening, a pressure servo system was utilized in isolated canine hearts. The system permits continuous monitoring of ventricular volume and control of diastolic and systolic pressures. After determination of the diastolic volume at zero filling pressure (V0), a series of variably preloaded or afterloaded contractions were generated including the isovolumic state. Contractile state was manipulated in a positive (calcium, 12-18 mg/100 ml; norepinephrine, 0.4-1.4 mug/min) or negative (propranolol, 0.12-0.50 mg/min) direction. Force and length terms derived for a thick-walled sphere were expressed per cross-sectional area of muscle and length, respectively, calculated at V0. For any preload, an inverse linear (r greater than 0.96) force-shortening relation was obtained, and each line was identified by its slope and isovolumic load (sigma0). Both slope and sigma0 increased with positive inotropic agents (vis-a-vis propranolol) or increments in preload. Thus, in the intact ventricle an inverse linear relation characterizes the force-shortening relation with the amount of shortening determined by initial fiber length, afterload, and the contractile state of the myocardium.", "contents": "Factors influencing left ventricular shortening in isolated canine heart. To assess in the intact ventricle the steady-state influence of several mechanical variables on the extent of left ventricular midwall circumferential shortening, a pressure servo system was utilized in isolated canine hearts. The system permits continuous monitoring of ventricular volume and control of diastolic and systolic pressures. After determination of the diastolic volume at zero filling pressure (V0), a series of variably preloaded or afterloaded contractions were generated including the isovolumic state. Contractile state was manipulated in a positive (calcium, 12-18 mg/100 ml; norepinephrine, 0.4-1.4 mug/min) or negative (propranolol, 0.12-0.50 mg/min) direction. Force and length terms derived for a thick-walled sphere were expressed per cross-sectional area of muscle and length, respectively, calculated at V0. For any preload, an inverse linear (r greater than 0.96) force-shortening relation was obtained, and each line was identified by its slope and isovolumic load (sigma0). Both slope and sigma0 increased with positive inotropic agents (vis-a-vis propranolol) or increments in preload. Thus, in the intact ventricle an inverse linear relation characterizes the force-shortening relation with the amount of shortening determined by initial fiber length, afterload, and the contractile state of the myocardium."} {"id": "PMID:1259024", "title": "Natriuresis induced by intracarotid infusion of hypertonic NaCl.", "content": "The intracarotid infusion of hypertonic sodium chloride in anesthetized dogs pretreated with vasopressin and mineralocorticoid resulted in an increase in sodium excretion as well as an increase in the percent of the filtered load of sodium excreted. This increase was not due to changes in renal hemodynamics or arterial blood pressure. The change in fractional sodium excretion was approximately 1%. Intracarotid infusion of isotonic sodium chloride did not result in a natriuretic response. The intracarotid infusion of hyperosmotic glucose did not evoke an increase in sodium excretion. Femoral vein infusions of hypertonic sodium chloride failed to evoke any natriuretic response. These data indicate that a sodium-sensing mechanism may exist in the brain that can alter the renal handling of sodium. The efferent mechanism of the response is discussed.", "contents": "Natriuresis induced by intracarotid infusion of hypertonic NaCl. The intracarotid infusion of hypertonic sodium chloride in anesthetized dogs pretreated with vasopressin and mineralocorticoid resulted in an increase in sodium excretion as well as an increase in the percent of the filtered load of sodium excreted. This increase was not due to changes in renal hemodynamics or arterial blood pressure. The change in fractional sodium excretion was approximately 1%. Intracarotid infusion of isotonic sodium chloride did not result in a natriuretic response. The intracarotid infusion of hyperosmotic glucose did not evoke an increase in sodium excretion. Femoral vein infusions of hypertonic sodium chloride failed to evoke any natriuretic response. These data indicate that a sodium-sensing mechanism may exist in the brain that can alter the renal handling of sodium. The efferent mechanism of the response is discussed."} {"id": "PMID:1259025", "title": "Calcium homeostasis during hypertonic volume expansion in the hypothyroid rat.", "content": "The clearance characteristics of calcium and the relationship of coupled Na+ and Ca++ renal transport were evaluated in the hypothyroid rat (TX) during volume expansion with 1.5% saline. Despite similar hydropenic plasma calcium, after 11 ml/100 g body wt of infusion volume, the plasma calcium was significantly lower in the TX group (TX, 6.1 +/- 0.2; TI, 7.0 +/- 0.1; P less than .001). With continued infusion, plasma calcium in the TX group continued to drop to 5.3 +/- 0.3 while in the control rats (TI group) it rose to 8.0 +/- 0.1. This marked hypocalcemia in the TX group could not be explained by urinary losses of calcium, hemodilution, deficient parathyroid response, or changes in ultrafilterable plasma calcium. The higher fractional calcium excretion found in the TX group paralleled the higher fractional sodium excretion, and the coupling between calcium and sodium excretion was preserved in hypothyroidism under these conditions. Our results indicate an abnormal calcium homeostasis in the hypothyroid rat. The data do not support a renal cause for this disturbance but are consistent with the view that mobilization of calcium from the bone is sluggish in hypothyroidism during volume expansion.", "contents": "Calcium homeostasis during hypertonic volume expansion in the hypothyroid rat. The clearance characteristics of calcium and the relationship of coupled Na+ and Ca++ renal transport were evaluated in the hypothyroid rat (TX) during volume expansion with 1.5% saline. Despite similar hydropenic plasma calcium, after 11 ml/100 g body wt of infusion volume, the plasma calcium was significantly lower in the TX group (TX, 6.1 +/- 0.2; TI, 7.0 +/- 0.1; P less than .001). With continued infusion, plasma calcium in the TX group continued to drop to 5.3 +/- 0.3 while in the control rats (TI group) it rose to 8.0 +/- 0.1. This marked hypocalcemia in the TX group could not be explained by urinary losses of calcium, hemodilution, deficient parathyroid response, or changes in ultrafilterable plasma calcium. The higher fractional calcium excretion found in the TX group paralleled the higher fractional sodium excretion, and the coupling between calcium and sodium excretion was preserved in hypothyroidism under these conditions. Our results indicate an abnormal calcium homeostasis in the hypothyroid rat. The data do not support a renal cause for this disturbance but are consistent with the view that mobilization of calcium from the bone is sluggish in hypothyroidism during volume expansion."} {"id": "PMID:1259026", "title": "Mechanics of canine iliac artery smooth muscle in vitro.", "content": "Transmural pressure and external diameter were continuously recorded from intact segments of canine iliac artery and used to determine wall responses to maximal smooth muscle (SM) activation by norepinephrine (NE). Three different approaches were used:a) step inflations from low pressure following NE, B) slow, continuous inflation from low pressure following NE, and c) direct isometric and isobaric responses to NE. Passive pressure-diameter data were determined. The results show that active wall stress and diameter responses to NE determined using direct isometric and isobaric responses and from slow inflation responses (less than 1 mmHg/s) were not significantly different. Pressure-diameter and stress-strain curves determined using continuous (0.2 mmHg/s) and step pressure inflations after NE were not signficantly different. Pressure-diameter curves obtained at different inflation rates were not those expected from a simple viscoelastic material. The results suggest that slow inflation of iliac arteries with activated SM is a reasonable method for assessing contractile properties of SM. Furthermore, they also suggest that activation of iliac artery SM at high contractile element length (L greater than Lo) does not produce attenuated constriction responses.", "contents": "Mechanics of canine iliac artery smooth muscle in vitro. Transmural pressure and external diameter were continuously recorded from intact segments of canine iliac artery and used to determine wall responses to maximal smooth muscle (SM) activation by norepinephrine (NE). Three different approaches were used:a) step inflations from low pressure following NE, B) slow, continuous inflation from low pressure following NE, and c) direct isometric and isobaric responses to NE. Passive pressure-diameter data were determined. The results show that active wall stress and diameter responses to NE determined using direct isometric and isobaric responses and from slow inflation responses (less than 1 mmHg/s) were not significantly different. Pressure-diameter and stress-strain curves determined using continuous (0.2 mmHg/s) and step pressure inflations after NE were not signficantly different. Pressure-diameter curves obtained at different inflation rates were not those expected from a simple viscoelastic material. The results suggest that slow inflation of iliac arteries with activated SM is a reasonable method for assessing contractile properties of SM. Furthermore, they also suggest that activation of iliac artery SM at high contractile element length (L greater than Lo) does not produce attenuated constriction responses."} {"id": "PMID:1259027", "title": "Tracer experiment design for unique identification of nonlinear physiological systems.", "content": "The design of tracer kinetic experiments, the purpose of which is to elucidate uniquely the internal couplings of a nonlinear dynamic system, is considered for a practical class of models of physiological systems. The extent of information about the real system contained in tracer kinetic data is a central issue. Criteria for determining whether nonlinear model parameters can be estimated from small-signal, \"linearizing\" tracer experiments are developed and illustrated by examples. The concept of \"structural identifiability\" is employed in this analysis to determine which model parameters can be and which cannot be determined \"uniquely\" from given input-output data; a step-by-step procedure based on an extension of this concept is presented for adapting the overall approach to the experimental design problem. Estimation of unmeasurable endogenous inputs and system state variables, problems that are intimately related to parameter estimation for physiological systems, are also considered.", "contents": "Tracer experiment design for unique identification of nonlinear physiological systems. The design of tracer kinetic experiments, the purpose of which is to elucidate uniquely the internal couplings of a nonlinear dynamic system, is considered for a practical class of models of physiological systems. The extent of information about the real system contained in tracer kinetic data is a central issue. Criteria for determining whether nonlinear model parameters can be estimated from small-signal, \"linearizing\" tracer experiments are developed and illustrated by examples. The concept of \"structural identifiability\" is employed in this analysis to determine which model parameters can be and which cannot be determined \"uniquely\" from given input-output data; a step-by-step procedure based on an extension of this concept is presented for adapting the overall approach to the experimental design problem. Estimation of unmeasurable endogenous inputs and system state variables, problems that are intimately related to parameter estimation for physiological systems, are also considered."} {"id": "PMID:1259028", "title": "Origin of great cardiac vein and coronary sinus drainage within the left ventricle.", "content": "The relative contributions of left anterior descending (LAD) and left circumflex (LC) arterial inflow to blood sampled at various points within the great cardiac vein (GCV) and coronary sinus (CS) have been investigated in open-chest dogs. Dissolved helium (He) and hydrogen (H2) were infused into external circuits perfusing the LAD and LC, respectively, and their steady-state concentrations were measured chromatographically at various points within the GCV and CS. Under basal conditions GCV H2 averaged only 5% of mid-CS H2 and did not change greatly during alterations of preload and afterload or during selective LAD or LC obstruction and vasodilation. The relationship of mid-CS He to GCV. He was more variable under basal conditions and changed noticeably during selective changes in LAD or LC inflow. Appreciable amounts of He were present consistently in left marginal vein drainage. We conclude that: 1) GCV blood is remarkably free of LC inflow in both normal and abnormal physiological states; 2) the origin of mid-CS blood is more variable, both from animal to animal and in individual animals before and after interventions; 3) a portion of LAD drainage normally reaches the CS through circumflex venous branches rather than the GCV.", "contents": "Origin of great cardiac vein and coronary sinus drainage within the left ventricle. The relative contributions of left anterior descending (LAD) and left circumflex (LC) arterial inflow to blood sampled at various points within the great cardiac vein (GCV) and coronary sinus (CS) have been investigated in open-chest dogs. Dissolved helium (He) and hydrogen (H2) were infused into external circuits perfusing the LAD and LC, respectively, and their steady-state concentrations were measured chromatographically at various points within the GCV and CS. Under basal conditions GCV H2 averaged only 5% of mid-CS H2 and did not change greatly during alterations of preload and afterload or during selective LAD or LC obstruction and vasodilation. The relationship of mid-CS He to GCV. He was more variable under basal conditions and changed noticeably during selective changes in LAD or LC inflow. Appreciable amounts of He were present consistently in left marginal vein drainage. We conclude that: 1) GCV blood is remarkably free of LC inflow in both normal and abnormal physiological states; 2) the origin of mid-CS blood is more variable, both from animal to animal and in individual animals before and after interventions; 3) a portion of LAD drainage normally reaches the CS through circumflex venous branches rather than the GCV."} {"id": "PMID:1259029", "title": "Neurons intrinsic to arterioles initiate postcontraction vasodilation.", "content": "Ganglion cells exist in muscle arterioles. To determine the role of these intrinsic neurons in postcontraction vasodilation, isolated dog gracilis muscles were studied. A single twitch elicited vasodilation, but no vasodilator metabolites appeared in the venous effluent. Contraction at 2/s lowered resistance within 1 s whereas dilator metabolites were not demonstrable in the effluent until 15-20 s. During contraction the magnitude and time course of vasodilation were the same during constant and variable flow, and at various values of PaO2 and PVO2. In contrast, resistance was strongly correlated with flow and PO2 during recovery. Some resting muscles were perfused with venous blood from contracting donors. The rate of metabolic vasodilation in recipient muscles was about 10 times less than the rate of vasodilation in the donors. Lidocaine and procaine blocked postcontraction vasodilation but did not influence postocclusion vasodilation, metabolic vasodialtion, or autoregulation. The degree of block was the same in acutely and chronically denervated muscles. The effect of local anesthetics could not be accounted for by properties of skeletal or vascular smooth muscles. 1) intrinsic neurons initiate postcontraction vasodilation; 2) metabolites account for sustained vasodilation during recovery.", "contents": "Neurons intrinsic to arterioles initiate postcontraction vasodilation. Ganglion cells exist in muscle arterioles. To determine the role of these intrinsic neurons in postcontraction vasodilation, isolated dog gracilis muscles were studied. A single twitch elicited vasodilation, but no vasodilator metabolites appeared in the venous effluent. Contraction at 2/s lowered resistance within 1 s whereas dilator metabolites were not demonstrable in the effluent until 15-20 s. During contraction the magnitude and time course of vasodilation were the same during constant and variable flow, and at various values of PaO2 and PVO2. In contrast, resistance was strongly correlated with flow and PO2 during recovery. Some resting muscles were perfused with venous blood from contracting donors. The rate of metabolic vasodilation in recipient muscles was about 10 times less than the rate of vasodilation in the donors. Lidocaine and procaine blocked postcontraction vasodilation but did not influence postocclusion vasodilation, metabolic vasodialtion, or autoregulation. The degree of block was the same in acutely and chronically denervated muscles. The effect of local anesthetics could not be accounted for by properties of skeletal or vascular smooth muscles. 1) intrinsic neurons initiate postcontraction vasodilation; 2) metabolites account for sustained vasodilation during recovery."} {"id": "PMID:1259030", "title": "Intracellular concentrations of the salt gland of the herring gull Larus argentatus.", "content": "Attempts were made to measure intra- and extracellular concentrations in secreting and inactive salt gland tissue of the herring gull. 14C-labeled polyethylene glycol (mol wt 4,000) was used as a marker for extracellular fluid. Fluid separated by centrifugation at 36,000 g appeared by three independent criteria to represent primarily extracellular fluid. It could not, however, be fully ascertained if this fluid was mixed with a small amount of intracellular fluid. Therefore, intracellular concentrations were calculated from the concentrations in centrifuged fluid as well as from plasma concentrations. By either method it was found that secreting and inactive glands showed no difference in extracellular and intracellular fluid concentrations of Na, K, Cl and Ca. Secreting glands had lower intracellular water content and a higher intracellular Mg concentration than inactive glands. The absence of evidence for intracellular accumulation of Na and Cl ions in secreting glands suggests that active ion transport takes place across the apical rather than the basal and lateral membranes in spite of the fact that Na-K-activated ATPase is associated with the extensive infoldings of these plasma membranes.", "contents": "Intracellular concentrations of the salt gland of the herring gull Larus argentatus. Attempts were made to measure intra- and extracellular concentrations in secreting and inactive salt gland tissue of the herring gull. 14C-labeled polyethylene glycol (mol wt 4,000) was used as a marker for extracellular fluid. Fluid separated by centrifugation at 36,000 g appeared by three independent criteria to represent primarily extracellular fluid. It could not, however, be fully ascertained if this fluid was mixed with a small amount of intracellular fluid. Therefore, intracellular concentrations were calculated from the concentrations in centrifuged fluid as well as from plasma concentrations. By either method it was found that secreting and inactive glands showed no difference in extracellular and intracellular fluid concentrations of Na, K, Cl and Ca. Secreting glands had lower intracellular water content and a higher intracellular Mg concentration than inactive glands. The absence of evidence for intracellular accumulation of Na and Cl ions in secreting glands suggests that active ion transport takes place across the apical rather than the basal and lateral membranes in spite of the fact that Na-K-activated ATPase is associated with the extensive infoldings of these plasma membranes."} {"id": "PMID:1259031", "title": "Nonshivering thermogenesis induced by repetitive hypothalamic cooling in the rat.", "content": "The effect of prolonged and repetitive cooling of the preoptic/anterior hypothalamic area on the sensitivity to the metabolic effect of noradrenaline and on the resistance to cold exposure was studied in the white rat. The preoptic area of 18 unanesthetized animals was cooled 9 h/day 5 days/wk, for a total of 80-150 h. One hour after a noradrenaline test injection (0.4 mg/kg), the experimental animals in which the preoptic area had been cooled to about 24 degrees C increased oxygen uptake by 81%, whereas those in which the preoptic area had been cooled to about 28 degrees C increased oxygen uptake by 48% (the control animals by only 37%). Despite their increased capacity for nonshivering thermogenesis, the experimental animals did not tolerate cold exposure (-10 degrees C) better than the controls. This development of nonshivering thermogenesis is thought to have been mediated by the hypothalamic temperature-sensitive neurons, and the possibility that it could explain the shift from shivering to nonshivering thermogenesis seen during adaptation to cold is discussed.", "contents": "Nonshivering thermogenesis induced by repetitive hypothalamic cooling in the rat. The effect of prolonged and repetitive cooling of the preoptic/anterior hypothalamic area on the sensitivity to the metabolic effect of noradrenaline and on the resistance to cold exposure was studied in the white rat. The preoptic area of 18 unanesthetized animals was cooled 9 h/day 5 days/wk, for a total of 80-150 h. One hour after a noradrenaline test injection (0.4 mg/kg), the experimental animals in which the preoptic area had been cooled to about 24 degrees C increased oxygen uptake by 81%, whereas those in which the preoptic area had been cooled to about 28 degrees C increased oxygen uptake by 48% (the control animals by only 37%). Despite their increased capacity for nonshivering thermogenesis, the experimental animals did not tolerate cold exposure (-10 degrees C) better than the controls. This development of nonshivering thermogenesis is thought to have been mediated by the hypothalamic temperature-sensitive neurons, and the possibility that it could explain the shift from shivering to nonshivering thermogenesis seen during adaptation to cold is discussed."} {"id": "PMID:1259032", "title": "Fluoride renal clearance: a pH-dependent event.", "content": "The renal clearance of fluoride (CF) was studied in pentobarbital-anesthetized rats. Urine flow rate and chloride clearance, previously thought to be the main determinants of CF, were readily dissociated from CF. Neither the clearance of sodium nor the excretion of potassium correlated consistently with CF. In experiments designed to manipulate urinary pH, viz., the administration of NaHCO3 or NH4Cl, acetazolamide, and mannitol, CF correlated closely with urinary pH. At a urinary pH of 5.0-k96, CF/GFR averaged less than 5%, while at a urinary pH of approximately 7.6, mean CF/GFR exceeded 65%. The data suggest that 35-45% of the filtered fluoride is reabsorbed in the proximal tubule, regardless of the final urinary pH, while in acidosis the majority of fluoride reabsorption occurs in the distal nephron. The results suggest that the tubular reabsorption of fluoride is inversely related to tubular fluid pH. Fluoride reabsorption seems to occur by nonionic diffusion, apparently as hydrogen fluoride. Depending on local pH gradients, it may occur along the entire nephron.", "contents": "Fluoride renal clearance: a pH-dependent event. The renal clearance of fluoride (CF) was studied in pentobarbital-anesthetized rats. Urine flow rate and chloride clearance, previously thought to be the main determinants of CF, were readily dissociated from CF. Neither the clearance of sodium nor the excretion of potassium correlated consistently with CF. In experiments designed to manipulate urinary pH, viz., the administration of NaHCO3 or NH4Cl, acetazolamide, and mannitol, CF correlated closely with urinary pH. At a urinary pH of 5.0-k96, CF/GFR averaged less than 5%, while at a urinary pH of approximately 7.6, mean CF/GFR exceeded 65%. The data suggest that 35-45% of the filtered fluoride is reabsorbed in the proximal tubule, regardless of the final urinary pH, while in acidosis the majority of fluoride reabsorption occurs in the distal nephron. The results suggest that the tubular reabsorption of fluoride is inversely related to tubular fluid pH. Fluoride reabsorption seems to occur by nonionic diffusion, apparently as hydrogen fluoride. Depending on local pH gradients, it may occur along the entire nephron."} {"id": "PMID:1259033", "title": "Site of kininogenase secretion in the dog nephron.", "content": "We determined the site of kininogenase secretion in the nephron by performing stop-flow studies in dogs. Kininogenase activity, inulin, sodium, and potassium were measured in the same fractions. The highest kininogenase concentration was found in the fractions with the lowest sodium concentration corresponding to urine samples that must have been trapped in the distal nephron. Kininogenases in these urine fractions were 5-17 times higher than in fractions from the proximal nephron or from the free-flow sample. The ratio of kininogenase increase to inulin increase was always higher than 3.0, thus indicating that the increase in kininogenase concentration was mainly due to secretion and not to water reabsorption. When a peak of potassium was present, it occurred 1-2 ml before the peak of kininogenases. We concluded that kininogenases are secreted into the urine at the level of the distal nephron by either the tubule itself or by a specialized structure located at this part of the nephron, such as the macula densa.", "contents": "Site of kininogenase secretion in the dog nephron. We determined the site of kininogenase secretion in the nephron by performing stop-flow studies in dogs. Kininogenase activity, inulin, sodium, and potassium were measured in the same fractions. The highest kininogenase concentration was found in the fractions with the lowest sodium concentration corresponding to urine samples that must have been trapped in the distal nephron. Kininogenases in these urine fractions were 5-17 times higher than in fractions from the proximal nephron or from the free-flow sample. The ratio of kininogenase increase to inulin increase was always higher than 3.0, thus indicating that the increase in kininogenase concentration was mainly due to secretion and not to water reabsorption. When a peak of potassium was present, it occurred 1-2 ml before the peak of kininogenases. We concluded that kininogenases are secreted into the urine at the level of the distal nephron by either the tubule itself or by a specialized structure located at this part of the nephron, such as the macula densa."} {"id": "PMID:1259034", "title": "Distribution of renal blood flow in dogs with congestive heart failure.", "content": "Studies were performed to determine whether the intrarenal distribution of cortical blood flow is altered in congestive heart failure. Utilizing the radioactive microsphere method, we studied eight dogs that developed congestive heart failure secondary to the construction of an aortocaval fistula. They had marked reduction in total renal blood flow not accompanied by intracortical redistribution of blood flow. All dogs had developed edema and/or ascites, and gained a mean of 3.4 kg; glomerular filtration rate, hematocrit, and urinary sodium excretion fell significantly. Renal vascular resistance increased; mean blood pressure and filtration fraction were unchanged. Furosemide was administered to a second group of nine fistula dogs. The drug produced a marked natriuresis associated with a decrease in outer cortical blood flow (zone 1) and an increase in midcortical zones 2 and 3; no change was observed in zone 4. We conclude: 1) chronic salt retention occurs in high-output heart failure in the absence of redistribution of renal cortical blood flow, and 2) the effect of furosemide on intrarenal hemodynamics of dogs with heart failure is similar to that seen in normal animals.", "contents": "Distribution of renal blood flow in dogs with congestive heart failure. Studies were performed to determine whether the intrarenal distribution of cortical blood flow is altered in congestive heart failure. Utilizing the radioactive microsphere method, we studied eight dogs that developed congestive heart failure secondary to the construction of an aortocaval fistula. They had marked reduction in total renal blood flow not accompanied by intracortical redistribution of blood flow. All dogs had developed edema and/or ascites, and gained a mean of 3.4 kg; glomerular filtration rate, hematocrit, and urinary sodium excretion fell significantly. Renal vascular resistance increased; mean blood pressure and filtration fraction were unchanged. Furosemide was administered to a second group of nine fistula dogs. The drug produced a marked natriuresis associated with a decrease in outer cortical blood flow (zone 1) and an increase in midcortical zones 2 and 3; no change was observed in zone 4. We conclude: 1) chronic salt retention occurs in high-output heart failure in the absence of redistribution of renal cortical blood flow, and 2) the effect of furosemide on intrarenal hemodynamics of dogs with heart failure is similar to that seen in normal animals."} {"id": "PMID:1259035", "title": "The psychological treatment of personality disorder.", "content": "The author presents three case reports of individuals with personality disorder, none of whom demonstrated significant ability for transitional relatedness before therapy. In therapy, he conceptualized for the two adult patients the importance of their inability to experience in the transitional mode; he offered concrete potential transitional objects to the one child patient. The therapeutic results were good.", "contents": "The psychological treatment of personality disorder. The author presents three case reports of individuals with personality disorder, none of whom demonstrated significant ability for transitional relatedness before therapy. In therapy, he conceptualized for the two adult patients the importance of their inability to experience in the transitional mode; he offered concrete potential transitional objects to the one child patient. The therapeutic results were good."} {"id": "PMID:1259036", "title": "Psychosurgery: some current observations.", "content": "The term \"psychosurgery\" encompasses a wide variety of different neurosurgical procedures applied in the treatment of behavioral and psychiatric disorders. Arguments about the effectiveness and ethicality of psychosurgery are often based on studies using outdated procedures or inappropriate patient populations. The debate over psychosurgery is also obscured by the frequent confusion between its use in classical psychiatric syndromes and in such controversial areas as aggression or violent behavior associated with temporal lobe epilepsy. The author believes that such factors need to be clarified so that practitioners can choose a personal position based on sound medical fact.", "contents": "Psychosurgery: some current observations. The term \"psychosurgery\" encompasses a wide variety of different neurosurgical procedures applied in the treatment of behavioral and psychiatric disorders. Arguments about the effectiveness and ethicality of psychosurgery are often based on studies using outdated procedures or inappropriate patient populations. The debate over psychosurgery is also obscured by the frequent confusion between its use in classical psychiatric syndromes and in such controversial areas as aggression or violent behavior associated with temporal lobe epilepsy. The author believes that such factors need to be clarified so that practitioners can choose a personal position based on sound medical fact."} {"id": "PMID:1259037", "title": "Therapy groups for women.", "content": "The author describes her experiences with two all-female psychotherapy groups, comparing these groups with both mixed-sex and consciousness-raising groups. Problems included a tendency of group members to drop out when dependency on the group became too intense and a lack of referrals to replace these dropouts, with resulting decreases in group size. The special strengths of such groups include the opportunity to concentrate on issues relevant to women, the possibility for development of a support system, the lack of sex-role divisions of labor, and the increased respect of members for other women and for themselves.", "contents": "Therapy groups for women. The author describes her experiences with two all-female psychotherapy groups, comparing these groups with both mixed-sex and consciousness-raising groups. Problems included a tendency of group members to drop out when dependency on the group became too intense and a lack of referrals to replace these dropouts, with resulting decreases in group size. The special strengths of such groups include the opportunity to concentrate on issues relevant to women, the possibility for development of a support system, the lack of sex-role divisions of labor, and the increased respect of members for other women and for themselves."} {"id": "PMID:1259038", "title": "A psychiatric study of patients referred with a diagnosis of hypoglycemia.", "content": "Five-hour oral glucose tolerance tests (GTTs) differentiated 30 volunteer patients who considered themselves hypoglycemic into three major groups: those who had reactive hypoglycemia, those who were normal, and those who had diabetes. Clinical psychiatric evaluation and Minnesota Multiphasic Personality Inventory testing revealed that half of the 30 patients were experiencing a current psychiatric disorder, usually depression. Hysterical personality traits were also noted in many of the patients. The idea that reactive hypoglycemic patients have specific personality characteristics was not substantiated by the authors' data. They hypothesize that some patients with psychiatric illness may have their symptoms erroneously attributed to incidental GTT findings.", "contents": "A psychiatric study of patients referred with a diagnosis of hypoglycemia. Five-hour oral glucose tolerance tests (GTTs) differentiated 30 volunteer patients who considered themselves hypoglycemic into three major groups: those who had reactive hypoglycemia, those who were normal, and those who had diabetes. Clinical psychiatric evaluation and Minnesota Multiphasic Personality Inventory testing revealed that half of the 30 patients were experiencing a current psychiatric disorder, usually depression. Hysterical personality traits were also noted in many of the patients. The idea that reactive hypoglycemic patients have specific personality characteristics was not substantiated by the authors' data. They hypothesize that some patients with psychiatric illness may have their symptoms erroneously attributed to incidental GTT findings."} {"id": "PMID:1259039", "title": "Disaster at Buffalo Creek. Family and character change at Buffalo Creek.", "content": "Psychiatric evaluation teams used observations of family interaction and psychoanalytically oriented individual interviews to study the psychological aftereffects of the 1972 Buffalo Creek disaster, a tidal wave of sludge and black water released by the collapse of a slag waste dam. Traumatic neurotic reactions were found in 80% of the survivors. Underlying the clinical picture were unresolved grief, survivor shame, and feelings of impotent rage and hopelessness. These clinical findings had persisted for the two years since the flood, and a definite symptom complex labeled the \"Buffalo Creek syndrome\" was pervasive. The methods used by the survivors to cope with the overwhelming impact of the disaster--first-order defenses, undoing, psychological conservatism, and dehumanization--actually preserved their symptoms and caused disabling character changes.", "contents": "Disaster at Buffalo Creek. Family and character change at Buffalo Creek. Psychiatric evaluation teams used observations of family interaction and psychoanalytically oriented individual interviews to study the psychological aftereffects of the 1972 Buffalo Creek disaster, a tidal wave of sludge and black water released by the collapse of a slag waste dam. Traumatic neurotic reactions were found in 80% of the survivors. Underlying the clinical picture were unresolved grief, survivor shame, and feelings of impotent rage and hopelessness. These clinical findings had persisted for the two years since the flood, and a definite symptom complex labeled the \"Buffalo Creek syndrome\" was pervasive. The methods used by the survivors to cope with the overwhelming impact of the disaster--first-order defenses, undoing, psychological conservatism, and dehumanization--actually preserved their symptoms and caused disabling character changes."} {"id": "PMID:1259040", "title": "Disaster at Buffalo Creek. From chaos to responsibility.", "content": "The litigation initiated by the 625 survivors of the Buffalo Creek flood who refused to settle with the coal company claims office was a landmark case. For the first time, individuals who were not present at the scene of a disaster were allowed to recover for mental injuries. Psychic impairment, the term coined for these injuries, was found in virtually all of the survivor-plaintiffs. In an out of court settlement, the survivors were awarded $13.5 million, $6 million of which was distributed on the basis of a point system as compensation for the psychological damages.", "contents": "Disaster at Buffalo Creek. From chaos to responsibility. The litigation initiated by the 625 survivors of the Buffalo Creek flood who refused to settle with the coal company claims office was a landmark case. For the first time, individuals who were not present at the scene of a disaster were allowed to recover for mental injuries. Psychic impairment, the term coined for these injuries, was found in virtually all of the survivor-plaintiffs. In an out of court settlement, the survivors were awarded $13.5 million, $6 million of which was distributed on the basis of a point system as compensation for the psychological damages."} {"id": "PMID:1259041", "title": "Disaster at Buffalo Creek. Loss of communality at Buffalo Creek.", "content": "The survivors of the Buffalo Creek disaster suffered both individual and collective trauma, the latter being reflected in their loss of communality. Human relationships in this community had been derived from traditional bonds of kinship and neighborliness. When forced to give up these long-standing ties with familiar places and people, the survivors experienced demoralization, disorientation, and loss of connection. Stripped of the support they had received from their community, they became apathetic and seemed to have forgotten how to care for one another. This was apparently a community that was stronger than the sum of its parts, and these parts--the survivors of the Buffalo Creek flood--are now having great difficulty finding the personal resources to replace the energy and direction they had once found in their community.", "contents": "Disaster at Buffalo Creek. Loss of communality at Buffalo Creek. The survivors of the Buffalo Creek disaster suffered both individual and collective trauma, the latter being reflected in their loss of communality. Human relationships in this community had been derived from traditional bonds of kinship and neighborliness. When forced to give up these long-standing ties with familiar places and people, the survivors experienced demoralization, disorientation, and loss of connection. Stripped of the support they had received from their community, they became apathetic and seemed to have forgotten how to care for one another. This was apparently a community that was stronger than the sum of its parts, and these parts--the survivors of the Buffalo Creek flood--are now having great difficulty finding the personal resources to replace the energy and direction they had once found in their community."} {"id": "PMID:1259042", "title": "Disaster at Buffalo Creek. Discussion of the Buffalo Creek disaster: the course of psychic trauma.", "content": "The specific contribution of the psychiatrist to the team study of the human disaster at Buffalo Creek focuses on the course of psychic trauma. The initial violent intrusion by the flood waters was followed by a second phase of the traumatic cycle, the physical dislocation of the survivors, with disruption of their \"ground\" and \"surround.\" During this long subsequent period the level of trauma did not recede but kept rising, although at a slower pace. Distant effects of the trauma may succeed the more immediate ones. The finite psychic space of the survivors is encroached upon by traumatic memories for an indefinite period of time, leaving fewer resources available for normal effective living. The absorption and merging of traumatic stimuli into a traumatophilia poses still another potential problem. The unprecedented legal decision as to the linear effects of psychic trauma on a succession of connected individuals will need further interdisciplinary clarification.", "contents": "Disaster at Buffalo Creek. Discussion of the Buffalo Creek disaster: the course of psychic trauma. The specific contribution of the psychiatrist to the team study of the human disaster at Buffalo Creek focuses on the course of psychic trauma. The initial violent intrusion by the flood waters was followed by a second phase of the traumatic cycle, the physical dislocation of the survivors, with disruption of their \"ground\" and \"surround.\" During this long subsequent period the level of trauma did not recede but kept rising, although at a slower pace. Distant effects of the trauma may succeed the more immediate ones. The finite psychic space of the survivors is encroached upon by traumatic memories for an indefinite period of time, leaving fewer resources available for normal effective living. The absorption and merging of traumatic stimuli into a traumatophilia poses still another potential problem. The unprecedented legal decision as to the linear effects of psychic trauma on a succession of connected individuals will need further interdisciplinary clarification."} {"id": "PMID:1259043", "title": "Carbon monoxide encephalopathy: need for appropriate treatment.", "content": "The authors describe severe psychiatric and neurological sequelae in a patient who suffered carbon monoxide poisoning as a result of a suicide attempt. A review of the literature revealed that 15 to 40% of survivors of carbon monoxide poisoning develop neuropsychiatric symptoms, often following a period of apparent recovery. The authors advocate an aggressive treatment approach to carbon monoxide poisoning, emphasize the diagnostic value of extensive laboratory testing, and suggest that 2 to 4 weeks of bedrest may prevent delayed neuropsychiatric sequelae.", "contents": "Carbon monoxide encephalopathy: need for appropriate treatment. The authors describe severe psychiatric and neurological sequelae in a patient who suffered carbon monoxide poisoning as a result of a suicide attempt. A review of the literature revealed that 15 to 40% of survivors of carbon monoxide poisoning develop neuropsychiatric symptoms, often following a period of apparent recovery. The authors advocate an aggressive treatment approach to carbon monoxide poisoning, emphasize the diagnostic value of extensive laboratory testing, and suggest that 2 to 4 weeks of bedrest may prevent delayed neuropsychiatric sequelae."} {"id": "PMID:1259044", "title": "Consultation-liaison psychiatry: current responsibilities.", "content": "The authors describe their experiences as consultation-liaison psychiatrists in two general teaching hospitals. Current medical house staff members appear to be more aware of the importance of psychosocial issues in patient care than were interns and residents in the past. Consultation-liaison teaching may now focus on the application of this psychologic awareness to patient management, the correct use of psychotropic drugs, and the differentiation of delirium from functional psychoses.", "contents": "Consultation-liaison psychiatry: current responsibilities. The authors describe their experiences as consultation-liaison psychiatrists in two general teaching hospitals. Current medical house staff members appear to be more aware of the importance of psychosocial issues in patient care than were interns and residents in the past. Consultation-liaison teaching may now focus on the application of this psychologic awareness to patient management, the correct use of psychotropic drugs, and the differentiation of delirium from functional psychoses."} {"id": "PMID:1259045", "title": "The role of the chief resident: expectations and reality.", "content": "The job expectations of 35 incoming chief residents were tested by questionnaire when they attended a weekend workshop on leadership and were reexamined after they has had six months' experience on their jobs. Such personal qualities as a sense of humor and persistence and such administrative skills as the ability to exercise authority and set objectives significantly increased in importance six months after these residents began work. The authors recommend educational programs in administration for chief residents.", "contents": "The role of the chief resident: expectations and reality. The job expectations of 35 incoming chief residents were tested by questionnaire when they attended a weekend workshop on leadership and were reexamined after they has had six months' experience on their jobs. Such personal qualities as a sense of humor and persistence and such administrative skills as the ability to exercise authority and set objectives significantly increased in importance six months after these residents began work. The authors recommend educational programs in administration for chief residents."} {"id": "PMID:1259046", "title": "The effect of haloperidol on stuttering.", "content": "Haloperidol was compared with placebo in the treatment of 8 young adult stutterers in a double-blind crossover study involving 6 sequential observations over periods of 6 or 12 weeks. The drug was found to have a significant effect on the percentage of time subjects were dysfluent but not on the number of dysfluencies per minute. The authors discuss possible reasons for this finding.", "contents": "The effect of haloperidol on stuttering. Haloperidol was compared with placebo in the treatment of 8 young adult stutterers in a double-blind crossover study involving 6 sequential observations over periods of 6 or 12 weeks. The drug was found to have a significant effect on the percentage of time subjects were dysfluent but not on the number of dysfluencies per minute. The authors discuss possible reasons for this finding."} {"id": "PMID:1259047", "title": "An evaluation of detoxification as an initial step in the treatment of heroin addiction.", "content": "Of 802 voluntary patients admitted to the detoxification unit of a comprehensive treatment system, 69% completed detoxification but only 9.6% of thest patients sought long-term treatment. The demographic profile of detoxification patients differed somewhat from that of patients in long-term treatment. The authors suggest that new approaches, including legal pressure, are needed to induce detoxification patients to accept prolonged therapy.", "contents": "An evaluation of detoxification as an initial step in the treatment of heroin addiction. Of 802 voluntary patients admitted to the detoxification unit of a comprehensive treatment system, 69% completed detoxification but only 9.6% of thest patients sought long-term treatment. The demographic profile of detoxification patients differed somewhat from that of patients in long-term treatment. The authors suggest that new approaches, including legal pressure, are needed to induce detoxification patients to accept prolonged therapy."} {"id": "PMID:1259048", "title": "The use of problem-oriented medical records in community mental health centers.", "content": "The authors' questionnaire survey of 147 community mental health centers revealed that 36 (24%) were using problem-oriented medical records (POMR), 34 (23%) planned to use them, 23 (16%) were uncertain and 54 (37%) had no considered using them. According to the responses of centers that were using POMR and the authors' experience, the advantages of POMR in psychiatry are similar to their advantages in other specialties, and the difficulties in implementing this system are related to the definition of \"problems.\"", "contents": "The use of problem-oriented medical records in community mental health centers. The authors' questionnaire survey of 147 community mental health centers revealed that 36 (24%) were using problem-oriented medical records (POMR), 34 (23%) planned to use them, 23 (16%) were uncertain and 54 (37%) had no considered using them. According to the responses of centers that were using POMR and the authors' experience, the advantages of POMR in psychiatry are similar to their advantages in other specialties, and the difficulties in implementing this system are related to the definition of \"problems.\""} {"id": "PMID:1259050", "title": "Orgone (Reichian) therapy in tension headache.", "content": "Orgone (Reichian) therapy, which utilizes a unique physical approach in addition to standard character-analysis, is illustrated in cases of muscle contraction (tension) headache. It offers a more direct technique for attacking the muscular tension (somatic armor) while undermining the psychic defenses.", "contents": "Orgone (Reichian) therapy in tension headache. Orgone (Reichian) therapy, which utilizes a unique physical approach in addition to standard character-analysis, is illustrated in cases of muscle contraction (tension) headache. It offers a more direct technique for attacking the muscular tension (somatic armor) while undermining the psychic defenses."} {"id": "PMID:1259051", "title": "Teaching dynamic psychotherapy by observation.", "content": "Experience with a seminar demonstrating psychotherapy, interviews with 12 of the treated patients, and a survey of 23 residents have shown the value of this teaching method and its effect on the participants. Generally the patients felt helped and residents were enthusiastic. The teaching format has many valuable features--most important being the inclusion of a faculty-observer.", "contents": "Teaching dynamic psychotherapy by observation. Experience with a seminar demonstrating psychotherapy, interviews with 12 of the treated patients, and a survey of 23 residents have shown the value of this teaching method and its effect on the participants. Generally the patients felt helped and residents were enthusiastic. The teaching format has many valuable features--most important being the inclusion of a faculty-observer."} {"id": "PMID:1259052", "title": "Communication and reality in the Capgras syndrome.", "content": "The study of a case of Capgras syndrome with striking clinical features illuminates the reality elements, affective conflicts, and cognitive processes that go into forming this specific delusion; and raises questions about the nosologic uniqueness of the entity. The meaning of the syndrome as a communication about an altered reality is highlighted.", "contents": "Communication and reality in the Capgras syndrome. The study of a case of Capgras syndrome with striking clinical features illuminates the reality elements, affective conflicts, and cognitive processes that go into forming this specific delusion; and raises questions about the nosologic uniqueness of the entity. The meaning of the syndrome as a communication about an altered reality is highlighted."} {"id": "PMID:1259053", "title": "Strategies and techniques of family therapy.", "content": "A conceptual model of the strategies and techniques of family therapy is presented. Attention is drawn to the complex relationships between the family therapist's manner of relating, the strategies and techniques which he or she employs, the presenting problem or problems, the particular characteristics of the family, and the development phase of the family therapy process.", "contents": "Strategies and techniques of family therapy. A conceptual model of the strategies and techniques of family therapy is presented. Attention is drawn to the complex relationships between the family therapist's manner of relating, the strategies and techniques which he or she employs, the presenting problem or problems, the particular characteristics of the family, and the development phase of the family therapy process."} {"id": "PMID:1259054", "title": "Psychotherapy with patients from lower socioeconomic groups.", "content": "Patients of lower socioeconomic status are only infrequently considered for individual psychodynamic psychotherapy even where cost is not a factor. Reasons for this bias are examined and suggestions are made for correcting such inadvertent discrimination.", "contents": "Psychotherapy with patients from lower socioeconomic groups. Patients of lower socioeconomic status are only infrequently considered for individual psychodynamic psychotherapy even where cost is not a factor. Reasons for this bias are examined and suggestions are made for correcting such inadvertent discrimination."} {"id": "PMID:1259055", "title": "Meditation and consciousness: an Asian approach to mental health.", "content": "According to Abhidhamma, a classical Asian phenomenology of consciousness, through meditation a set of \"healthy\" mental properties reciprocally inhibits an \"unhealthy\" set. In light of Abhidhamma and empirical findings, applications of meditation are suggested for inducing an optimal mode of responsiveness to environmental demands, and as a complementary adjunct to psychotherapy.", "contents": "Meditation and consciousness: an Asian approach to mental health. According to Abhidhamma, a classical Asian phenomenology of consciousness, through meditation a set of \"healthy\" mental properties reciprocally inhibits an \"unhealthy\" set. In light of Abhidhamma and empirical findings, applications of meditation are suggested for inducing an optimal mode of responsiveness to environmental demands, and as a complementary adjunct to psychotherapy."} {"id": "PMID:1259056", "title": "Learning theory and gestalt therapy.", "content": "This article discusses the theory and operations of Gestalt Therapy from the viewpoint of learning theory. General comparative issues are elaborated as well as the concepts of introjection, retroflextion, confluence, and projection. Principles and techniques of Gestalt Therapy are discussed in terms of learning theory paradigm. Practical implications of the various Gestalt techniques are presented.", "contents": "Learning theory and gestalt therapy. This article discusses the theory and operations of Gestalt Therapy from the viewpoint of learning theory. General comparative issues are elaborated as well as the concepts of introjection, retroflextion, confluence, and projection. Principles and techniques of Gestalt Therapy are discussed in terms of learning theory paradigm. Practical implications of the various Gestalt techniques are presented."} {"id": "PMID:1259057", "title": "\"Joining techniques\" in the treatment of resistant children and adolescents.", "content": "Several clinical vignettes illustrate types of resistive children and adolescents: the shrugger, the silent child, the rose-colored-glass child, the mistrustful adolescent, the cheater and rule changer, the thrower. Several joining techniques are demonstrated such as hypervaluing, tutoring the therapist, ordering, and mirroring. Limited anxiety enhanced ego strength, and facilitated therapy result. Neal Miller's conflict model provides a theoretical framework for the approach.", "contents": "\"Joining techniques\" in the treatment of resistant children and adolescents. Several clinical vignettes illustrate types of resistive children and adolescents: the shrugger, the silent child, the rose-colored-glass child, the mistrustful adolescent, the cheater and rule changer, the thrower. Several joining techniques are demonstrated such as hypervaluing, tutoring the therapist, ordering, and mirroring. Limited anxiety enhanced ego strength, and facilitated therapy result. Neal Miller's conflict model provides a theoretical framework for the approach."} {"id": "PMID:1259058", "title": "Selective group approaches with psychotic patients in hospital settings.", "content": "This paper stresses the group treatment of psychotics, with special reference to the schizophrenic. It includes interrelated groups structured on a graded scale and differentiated by the degree of its members' regressive levels of fixation. The patients' emotional and functional capacities decide suitability and selection. This group system simplifies criteria for composition, techniques, and the therapist's role.", "contents": "Selective group approaches with psychotic patients in hospital settings. This paper stresses the group treatment of psychotics, with special reference to the schizophrenic. It includes interrelated groups structured on a graded scale and differentiated by the degree of its members' regressive levels of fixation. The patients' emotional and functional capacities decide suitability and selection. This group system simplifies criteria for composition, techniques, and the therapist's role."} {"id": "PMID:1259061", "title": "An evaluation of selected federal categorical health programs for the poor.", "content": "We examine evidence regarding the impact of several categorical federal health service programs--neighborhood health centers, maternal and infant care projects, and children and youth projects--on access to and quality of health care for the poor. We conclude that, although conclusive evidence of improved access and quality are lacking, suggestive evidence of improved quality exists. It is difficult to utilize legislative objectives as guidelines for evaluating the success of a federal program; it is also difficult to obtain solid data supporting the effectiveness or ineffectiveness of health care in general, and of other government programs. These difficulties are discussed.", "contents": "An evaluation of selected federal categorical health programs for the poor. We examine evidence regarding the impact of several categorical federal health service programs--neighborhood health centers, maternal and infant care projects, and children and youth projects--on access to and quality of health care for the poor. We conclude that, although conclusive evidence of improved access and quality are lacking, suggestive evidence of improved quality exists. It is difficult to utilize legislative objectives as guidelines for evaluating the success of a federal program; it is also difficult to obtain solid data supporting the effectiveness or ineffectiveness of health care in general, and of other government programs. These difficulties are discussed."} {"id": "PMID:1259062", "title": "Problems in the nutritional assessment of black individuals.", "content": "Nutritional assessment of American Negro (Black) individuals of largely-African ancestry is complicated by differences that transcend socioeconomic status (SES). These include smaller size at birth but greater size from 2 to 14 years, advanced skeletal development (\"bone age\"), advanced dental development, a larger skeletal mass and bone \"density\" and a lesser rate of adult bone loss in the Black female from age 40 on as shown in a variety of bone-losing situtations, including renal osteodystrophies. Thus, appropriate dimensional and radiographic and radiogrammetric measures must be employed. Differences in hemoglobin concentration approximating 1.0g/100ml and in hematocrit levels also indicate the need for population-specific standards, otherwise gross errors will be made in calculating the per cent \"deficient\" and \"low\". Since self-assignments to racial categories are commonly used, the problem of racial identification is minimal. Failure to employ appropriate standards will result in underestimating the dimensional, radiographic and radiogrammetric effects of undernutrition in Blacks after the 2nd year, underestimating adult bone loss to a large degree, but overestimating the severity of hematologic responses from the 1st year through the 9th decade.", "contents": "Problems in the nutritional assessment of black individuals. Nutritional assessment of American Negro (Black) individuals of largely-African ancestry is complicated by differences that transcend socioeconomic status (SES). These include smaller size at birth but greater size from 2 to 14 years, advanced skeletal development (\"bone age\"), advanced dental development, a larger skeletal mass and bone \"density\" and a lesser rate of adult bone loss in the Black female from age 40 on as shown in a variety of bone-losing situtations, including renal osteodystrophies. Thus, appropriate dimensional and radiographic and radiogrammetric measures must be employed. Differences in hemoglobin concentration approximating 1.0g/100ml and in hematocrit levels also indicate the need for population-specific standards, otherwise gross errors will be made in calculating the per cent \"deficient\" and \"low\". Since self-assignments to racial categories are commonly used, the problem of racial identification is minimal. Failure to employ appropriate standards will result in underestimating the dimensional, radiographic and radiogrammetric effects of undernutrition in Blacks after the 2nd year, underestimating adult bone loss to a large degree, but overestimating the severity of hematologic responses from the 1st year through the 9th decade."} {"id": "PMID:1259063", "title": "Health care and disease prevention through genetic counseling: a regional approach.", "content": "The Colorado-Wyoming Regional Genetic Counseling Program has demonstrated the feasibility and utility of providing genetic counseling services over a very large area of the Rocky Mountain Region. A basis for preventing genetic and congenital disorders has been established and the patient care provided has been as comprehensive, sophisticated and effective as for any genetic counseling clinic operating in a medical center, with the added advantage of being accessible to a much larger and less financially able patient population. Utilization data and consumer assessment of the values of this service confirm these impressions.", "contents": "Health care and disease prevention through genetic counseling: a regional approach. The Colorado-Wyoming Regional Genetic Counseling Program has demonstrated the feasibility and utility of providing genetic counseling services over a very large area of the Rocky Mountain Region. A basis for preventing genetic and congenital disorders has been established and the patient care provided has been as comprehensive, sophisticated and effective as for any genetic counseling clinic operating in a medical center, with the added advantage of being accessible to a much larger and less financially able patient population. Utilization data and consumer assessment of the values of this service confirm these impressions."} {"id": "PMID:1259064", "title": "The front line health worker: selection, training, and performance.", "content": "Iranian villagers with basic literacy were recruited, selected, trained, and deployed as Village Health Workers (VHWs) to rural areas of Iran. VHW clinical visit records and activities logs were analyzed to determine levels and nature of effort achieved in the field. Within six months of deployment, the number of patient visits to VHW treatment services constituted 53% of the target population. Within ten months of deployment, the number of family planning acceptors rose from 8% to 21% of the population at risk. Improvements to water supplies have been effected in 50% of target villages. Sanitary improvements have been made to 35% of the houses and 88% of toilets in those villages. Demographic characteristics, class rank, and place of residence of VHWs appear unassociated with village differences in levels of achievement. However, availability of material resources and actual time spent by VHWs on the job may be factors influencing the differences in outcome between villages.", "contents": "The front line health worker: selection, training, and performance. Iranian villagers with basic literacy were recruited, selected, trained, and deployed as Village Health Workers (VHWs) to rural areas of Iran. VHW clinical visit records and activities logs were analyzed to determine levels and nature of effort achieved in the field. Within six months of deployment, the number of patient visits to VHW treatment services constituted 53% of the target population. Within ten months of deployment, the number of family planning acceptors rose from 8% to 21% of the population at risk. Improvements to water supplies have been effected in 50% of target villages. Sanitary improvements have been made to 35% of the houses and 88% of toilets in those villages. Demographic characteristics, class rank, and place of residence of VHWs appear unassociated with village differences in levels of achievement. However, availability of material resources and actual time spent by VHWs on the job may be factors influencing the differences in outcome between villages."} {"id": "PMID:1259068", "title": "An introductory course in prescription drugs for community health workers developed by a systems approach.", "content": "A 16-hour introductory course in prescription drugs for community health workers was developed by a systems approach. It featured an emphasis on: (1) learning the broad indications, side effects, and adverse reactions of the 30 most commonly prescribed drugs in the outpatient clinic, and (2) aiding the workers in patient education. Teaching materials were simple and inexpensive. An evaluation based on a pretest of the course's objectives compared to a final test documented the success of the instruction.", "contents": "An introductory course in prescription drugs for community health workers developed by a systems approach. A 16-hour introductory course in prescription drugs for community health workers was developed by a systems approach. It featured an emphasis on: (1) learning the broad indications, side effects, and adverse reactions of the 30 most commonly prescribed drugs in the outpatient clinic, and (2) aiding the workers in patient education. Teaching materials were simple and inexpensive. An evaluation based on a pretest of the course's objectives compared to a final test documented the success of the instruction."} {"id": "PMID:1259074", "title": "Renal involvement in patients with hepatosplenic Schistosomiasis mansoni.", "content": "In a prospective study of renal involvement in 100 consecutively hospitalized patients with hepatosplenic schistosomiasis mansoni, 15 exhibited persistent proteinuria of varying degree, which in 6 instances was accompanied by hypertension. Nine patients had the nephrotic syndrome. The most common glomerular lesion in this group was membrano-proliferative glomerulonephritis. Surgical biospy obtained during splenectomy in 15 patients without clinical evidence of renal involvement showed glomerular lesions in 6 instances. Focal proliferative glomerulonephritis was the most common lesion in this group. The detection of silent glomerular lesions in patients with Schistosoma mansoni infection suggests that the glomerular alterations may precede clinical manifestations of renal disease.", "contents": "Renal involvement in patients with hepatosplenic Schistosomiasis mansoni. In a prospective study of renal involvement in 100 consecutively hospitalized patients with hepatosplenic schistosomiasis mansoni, 15 exhibited persistent proteinuria of varying degree, which in 6 instances was accompanied by hypertension. Nine patients had the nephrotic syndrome. The most common glomerular lesion in this group was membrano-proliferative glomerulonephritis. Surgical biospy obtained during splenectomy in 15 patients without clinical evidence of renal involvement showed glomerular lesions in 6 instances. Focal proliferative glomerulonephritis was the most common lesion in this group. The detection of silent glomerular lesions in patients with Schistosoma mansoni infection suggests that the glomerular alterations may precede clinical manifestations of renal disease."} {"id": "PMID:1259075", "title": "Mycobacterium ulcerans (Buruli) skin ulceration in Nigeria.", "content": "Twenty-two of 24 cases of Mycobacterium ulcerans infection in Ibadan are reviewed. The patients included Africans, Caucasians, and Indians. There were no differences between races in the manifestations of the disease. The average age of the patients was higher than that in other reports in the literature. The fact that most cases were originally wrongly diagnosed reemphasizes the need to search for M. ulcerans in cases of \"tropical\" ulcer that fail to respond to adequate therapy. Early recognition and surgery are the mainstay of treatment. Comexazole seems more effective than clofazimine in the treatment of these ulcers.", "contents": "Mycobacterium ulcerans (Buruli) skin ulceration in Nigeria. Twenty-two of 24 cases of Mycobacterium ulcerans infection in Ibadan are reviewed. The patients included Africans, Caucasians, and Indians. There were no differences between races in the manifestations of the disease. The average age of the patients was higher than that in other reports in the literature. The fact that most cases were originally wrongly diagnosed reemphasizes the need to search for M. ulcerans in cases of \"tropical\" ulcer that fail to respond to adequate therapy. Early recognition and surgery are the mainstay of treatment. Comexazole seems more effective than clofazimine in the treatment of these ulcers."} {"id": "PMID:1259076", "title": "Cryptococcal granuloma (toruloma) of the central nervous system in a patient with schistosomiasis.", "content": "A case of cryptococcal granuloma of the brain and lung is described in a Nigerian woman who also had Schistosoma haematobium infection.", "contents": "Cryptococcal granuloma (toruloma) of the central nervous system in a patient with schistosomiasis. A case of cryptococcal granuloma of the brain and lung is described in a Nigerian woman who also had Schistosoma haematobium infection."} {"id": "PMID:1259077", "title": "Chromomycosis: a clinical and mycologic study of thirty-five cases observed in the hinterland of Rio Grande do Sul, Brazil.", "content": "Data on thirty-five patients with chromomycosis seen in the hinterland of the State of Rio Grande do Sul (Brazil) are reviewed. Atypical lesions were found in 28.5% of the patients. The lesions were localized on the upper limbs and face in 14.2% and 8.5% of the patients, respectively. The clinical aspects and mycologic diagnosis of chromomycosis are discussed, and an account is given of its regional distribution in Rio Grande do Sul.", "contents": "Chromomycosis: a clinical and mycologic study of thirty-five cases observed in the hinterland of Rio Grande do Sul, Brazil. Data on thirty-five patients with chromomycosis seen in the hinterland of the State of Rio Grande do Sul (Brazil) are reviewed. Atypical lesions were found in 28.5% of the patients. The lesions were localized on the upper limbs and face in 14.2% and 8.5% of the patients, respectively. The clinical aspects and mycologic diagnosis of chromomycosis are discussed, and an account is given of its regional distribution in Rio Grande do Sul."} {"id": "PMID:1259078", "title": "Dengue outbreaks in Gu\u00e1nica-Ensenada and Villalba, Puerto Rico, 1972-1973.", "content": "Epidemics of dengue fever occurring in Puerto Rico in 1963 to 1964 and 1969 were caused by dengue-3 and dengue-2 (DN-2) viruses, respectively, but endemic dengue transmission has never been documented on the Island. Since the 1969 epidemic, a surveillance system has detected DN-2 activity on the Island during each of the years 1970 through 1973, which suggests endemic persistence of the virus. This report describes the investigation of localized outbreaks of DN-2 in Guanica-Ensenada (1972) and Villalba (1973), and presents epidemiological, serological, and virological data from the outbreaks. Analysis of geographic distribution of dengue activity in Puerto Rico in recent years indicates that the DN-2 transmission in 1970 to 1973 may represent a long tail-off of the 1969 epidemic rather than the emergence of a truly endemic situation.", "contents": "Dengue outbreaks in Gu\u00e1nica-Ensenada and Villalba, Puerto Rico, 1972-1973. Epidemics of dengue fever occurring in Puerto Rico in 1963 to 1964 and 1969 were caused by dengue-3 and dengue-2 (DN-2) viruses, respectively, but endemic dengue transmission has never been documented on the Island. Since the 1969 epidemic, a surveillance system has detected DN-2 activity on the Island during each of the years 1970 through 1973, which suggests endemic persistence of the virus. This report describes the investigation of localized outbreaks of DN-2 in Guanica-Ensenada (1972) and Villalba (1973), and presents epidemiological, serological, and virological data from the outbreaks. Analysis of geographic distribution of dengue activity in Puerto Rico in recent years indicates that the DN-2 transmission in 1970 to 1973 may represent a long tail-off of the 1969 epidemic rather than the emergence of a truly endemic situation."} {"id": "PMID:1259079", "title": "Experimental transmission of trivittatus virus (California virus group) by Aedes trivittatus.", "content": "The mosquito, Aedes trivittatus, when fed through a membrane a trivittatus virus dosage of 10(3.4) to 10(5.5) suckling mouse LD50/0.03 ml of blood, transmitted the virus to suckling mice. Virus multiplication indicative of a biological vector occurred in this species. When Aedes vexans and A. triseriatus ingested similar doses of trivittatus virus, both the infection and transmission rates were low and virus multiplication was poor. These results, added to evidence based on virus isolations from mosqito populations in nature, indicate that A. trivittatus is the primary vector of trivittatus virus in the north central United States.", "contents": "Experimental transmission of trivittatus virus (California virus group) by Aedes trivittatus. The mosquito, Aedes trivittatus, when fed through a membrane a trivittatus virus dosage of 10(3.4) to 10(5.5) suckling mouse LD50/0.03 ml of blood, transmitted the virus to suckling mice. Virus multiplication indicative of a biological vector occurred in this species. When Aedes vexans and A. triseriatus ingested similar doses of trivittatus virus, both the infection and transmission rates were low and virus multiplication was poor. These results, added to evidence based on virus isolations from mosqito populations in nature, indicate that A. trivittatus is the primary vector of trivittatus virus in the north central United States."} {"id": "PMID:1259080", "title": "Studies on x-ray induced chromosomal translocations in Anopheles albimanus. III. Effect of the release of translocation males on the dynamics of cage populations.", "content": "Anopheles albimanus males carrying an Y-autosome translocation were continuously released into a cage population at a ratio of 1:5 in favor of translocation males. The release caused a significant decrease in the absolute density of cage populations. Virtually complete replacement of wild type Y chromosome by translocated Y chromosome was observed after four generations. The results obtained from the cage experiments encourage actual field trials for the control of this vector species.", "contents": "Studies on x-ray induced chromosomal translocations in Anopheles albimanus. III. Effect of the release of translocation males on the dynamics of cage populations. Anopheles albimanus males carrying an Y-autosome translocation were continuously released into a cage population at a ratio of 1:5 in favor of translocation males. The release caused a significant decrease in the absolute density of cage populations. Virtually complete replacement of wild type Y chromosome by translocated Y chromosome was observed after four generations. The results obtained from the cage experiments encourage actual field trials for the control of this vector species."} {"id": "PMID:1259081", "title": "Microfilaria of Wuchereria bancrofti in bone marrow smear.", "content": "Microfilariae of Wuchereria bancrofti were detected in seven cases of anemia in persons with asymptomatic filariasis. In three cases microfilariae could not be detected in the blood. Their presence in bone marrow may indicate the ability of microfilariae to cross the vessel wall.", "contents": "Microfilaria of Wuchereria bancrofti in bone marrow smear. Microfilariae of Wuchereria bancrofti were detected in seven cases of anemia in persons with asymptomatic filariasis. In three cases microfilariae could not be detected in the blood. Their presence in bone marrow may indicate the ability of microfilariae to cross the vessel wall."} {"id": "PMID:1259082", "title": "The prevalence of toxoplasmosis on Pacific Islands, and the influence of ethnic group.", "content": "The prevalence of Toxoplasma dye-test antibody was determined in inhabitants of a number of Pacific islands, in Melanesia, Micronesia and Polynesia, and on Taiwan. With the exception of one island in French Polynesia, two Hawaiian islands, and Taiwan, Toxoplasma antibody prevalences were high, ranging between 84% and 100% in the adult populations tested. On the Hawaiian islands of Oahu and Hawaii, populated by several ethnic groups, and where about 50% of the total adult populations were estimated to have been infected with Toxoplasma gondii, a marked variation in prevalence of infection by ethnic group was observed. The lowest prevalence in the Hawaiian islands estimated at about 15% to 20% in adults, was observed in Japanese. On Taiwan, only 6% of adult ethnic Chinese and 1% of aborigines tested had Toxoplasma antibody.", "contents": "The prevalence of toxoplasmosis on Pacific Islands, and the influence of ethnic group. The prevalence of Toxoplasma dye-test antibody was determined in inhabitants of a number of Pacific islands, in Melanesia, Micronesia and Polynesia, and on Taiwan. With the exception of one island in French Polynesia, two Hawaiian islands, and Taiwan, Toxoplasma antibody prevalences were high, ranging between 84% and 100% in the adult populations tested. On the Hawaiian islands of Oahu and Hawaii, populated by several ethnic groups, and where about 50% of the total adult populations were estimated to have been infected with Toxoplasma gondii, a marked variation in prevalence of infection by ethnic group was observed. The lowest prevalence in the Hawaiian islands estimated at about 15% to 20% in adults, was observed in Japanese. On Taiwan, only 6% of adult ethnic Chinese and 1% of aborigines tested had Toxoplasma antibody."} {"id": "PMID:1259083", "title": "Angiostrongylus cantonensis: lymphoid cell responsiveness and antibody production in rats.", "content": "Angiostrongylus cantonensis-infected rats were examined for the presence of antigen sensitive lymphocytes, as assessed by the in vitro uptake of tritiated thymidine by cells of various lymphoid organs (cervical, mediastinal and mesenteric lymph nodes, spleen and periphereal blood), following stimulation by adult worm antigen. The lymphoid cell response of rats to A. cantonensis appeared to be local in nature in that significant responses were noted only in the cervical lymph node cells during the first 4 weeks of infection. The responses of spleen cells to phytohemagglutinin gradually declined as the infection progressed and this reduced responsiveness was statistically significant during the period of 5 to 10 weeks of infection. Homocytotropic antibody, demonstrated by 72-hour homologous passive cutaneous anaphylaxis, was detected throughout 2 to 17 weeks postinfection with a peak response at the 5th week of infection. The antibody was heat labile and sensitive to reduction by 2-mercaptoethanol and alkylation. Hemagglutinating antibody was first observed 5 weeks after infection and high titers occurred throughout 6 to 17 weeks postinfection.", "contents": "Angiostrongylus cantonensis: lymphoid cell responsiveness and antibody production in rats. Angiostrongylus cantonensis-infected rats were examined for the presence of antigen sensitive lymphocytes, as assessed by the in vitro uptake of tritiated thymidine by cells of various lymphoid organs (cervical, mediastinal and mesenteric lymph nodes, spleen and periphereal blood), following stimulation by adult worm antigen. The lymphoid cell response of rats to A. cantonensis appeared to be local in nature in that significant responses were noted only in the cervical lymph node cells during the first 4 weeks of infection. The responses of spleen cells to phytohemagglutinin gradually declined as the infection progressed and this reduced responsiveness was statistically significant during the period of 5 to 10 weeks of infection. Homocytotropic antibody, demonstrated by 72-hour homologous passive cutaneous anaphylaxis, was detected throughout 2 to 17 weeks postinfection with a peak response at the 5th week of infection. The antibody was heat labile and sensitive to reduction by 2-mercaptoethanol and alkylation. Hemagglutinating antibody was first observed 5 weeks after infection and high titers occurred throughout 6 to 17 weeks postinfection."} {"id": "PMID:1259085", "title": "Clinical observations on eosinophilic meningitis and meningoencephalitis caused by Angiostrongylus cantonensis on Taiwan.", "content": "One hundred and twenty-five patients with eosinophilic meningitis or meningoencephalitis were studied in southern Taiwan in 1968 and 1969. The majority of patients had mild to moderate disease, but several had severe manifestations. Four patients died and three others had severe permanent sequelae such as blindness. Young adult Angiostrongylus cantonensis were recovered from nine patients, at autopsy in one, and from the cerebrospinal fluid of eight who survived. The clinical manifestations of cases of proven etiology were similar to those of cases from which parasites were not recovered and it is believed that the latter also were the result of infection with A. cantonensis.", "contents": "Clinical observations on eosinophilic meningitis and meningoencephalitis caused by Angiostrongylus cantonensis on Taiwan. One hundred and twenty-five patients with eosinophilic meningitis or meningoencephalitis were studied in southern Taiwan in 1968 and 1969. The majority of patients had mild to moderate disease, but several had severe manifestations. Four patients died and three others had severe permanent sequelae such as blindness. Young adult Angiostrongylus cantonensis were recovered from nine patients, at autopsy in one, and from the cerebrospinal fluid of eight who survived. The clinical manifestations of cases of proven etiology were similar to those of cases from which parasites were not recovered and it is believed that the latter also were the result of infection with A. cantonensis."} {"id": "PMID:1259086", "title": "Clinical and laboratory changes consequent to diethylcarbamazine in patients with onchocerciasis.", "content": "This controlled study assesses the effect of a single oral dose of diethylcarbamazine (DEC) in a Guatemalan population with light infections of Onchocerca volvulus. From 8 to 24 hours after DEC, microfilariae were found with increased frequency in the urine, blood, and sputum, while the number of microfilariae per mm2 of skin decreased. The onset of signs and symptoms of reaction coincided with the appearance of microfilariae in the body fluids. Motile microfilariae were noted in the anterior chamber of the eye after the administration of diethylcarbamazine. Medication with corticosteroids appeared to reduce the symptoms of reaction without changing the laboratory results.", "contents": "Clinical and laboratory changes consequent to diethylcarbamazine in patients with onchocerciasis. This controlled study assesses the effect of a single oral dose of diethylcarbamazine (DEC) in a Guatemalan population with light infections of Onchocerca volvulus. From 8 to 24 hours after DEC, microfilariae were found with increased frequency in the urine, blood, and sputum, while the number of microfilariae per mm2 of skin decreased. The onset of signs and symptoms of reaction coincided with the appearance of microfilariae in the body fluids. Motile microfilariae were noted in the anterior chamber of the eye after the administration of diethylcarbamazine. Medication with corticosteroids appeared to reduce the symptoms of reaction without changing the laboratory results."} {"id": "PMID:1259087", "title": "The homocytotropic and hemagglutinating antibody responses to Brugia pahangi infection in the multimammate rat (Mastomys natalensis).", "content": "Homocytotropic and hemagglutinating antibody responses were followed in multimammate rate (Mastomys natalensis) infected with Brugia pahangi. Homocytotropic antibodies were detected by both active and passive cutaneous anaphylaxis using an antigen prepared from Dirofilaria immitis. The homocytotropic antibody response was first evident at 3 weeks after infection and increased progressively until after patency. It then waned gradually and was absent at 33 weeks after infection (or 20 weeks after patency). During this time microfilaremia continued to increase steadily. Homocytotropic antibody induced by the infection was heat (56 degrees C) labile, sensitive to 2-mercaptoethanol reduction, and was detected in the skin of recipients following a 72-hour latent period. Hemagglutinating antibodies to the infection were detected by the D. immitis antigen. These were present by 9 days after infection and persisted throughout the course of the infection. Only 2-mercaptoethanol labile antibody was detected during the prepatent period of infection.", "contents": "The homocytotropic and hemagglutinating antibody responses to Brugia pahangi infection in the multimammate rat (Mastomys natalensis). Homocytotropic and hemagglutinating antibody responses were followed in multimammate rate (Mastomys natalensis) infected with Brugia pahangi. Homocytotropic antibodies were detected by both active and passive cutaneous anaphylaxis using an antigen prepared from Dirofilaria immitis. The homocytotropic antibody response was first evident at 3 weeks after infection and increased progressively until after patency. It then waned gradually and was absent at 33 weeks after infection (or 20 weeks after patency). During this time microfilaremia continued to increase steadily. Homocytotropic antibody induced by the infection was heat (56 degrees C) labile, sensitive to 2-mercaptoethanol reduction, and was detected in the skin of recipients following a 72-hour latent period. Hemagglutinating antibodies to the infection were detected by the D. immitis antigen. These were present by 9 days after infection and persisted throughout the course of the infection. Only 2-mercaptoethanol labile antibody was detected during the prepatent period of infection."} {"id": "PMID:1259089", "title": "The intensity and effects of infection with Schistosoma mansoni in a rural community in northeast Brazil.", "content": "The intensity of infection with Schistosoma mansoni and its effects were investigated in a defined population living on three contiguous fazendas (subcounties) in a nonmalarious area of northeast Brazil near Salvador, Bahia. Quantitative stool egg counts (Bell technique) were performed on 363 of 417 individuals (90%) of all ages; physical examinations were done on 294 of 357 individuals (82%) 5 years of age and older. The maximum increase in prevalence was observed between the 1- to 4- and 5- to 9-year age groups, while the maximum increase in fecal egg count occurred between 5- to 9- and 10- to 14-year age groups. Highest egg counts were observed in the 10- to 14-year age group (geometric mean of 301 eggs per ml of stool) while the maximum prevalence (100%) was in the 20- to 24-year age group. In the fazenda with the lowest quantitative egg counts the age specific prevalence rates increased more slowly than in the fazendas with higher egg counts. In the study group nearly 50% of the total fecal egg output was accounted for by 22 individuals (6%) who had a mean age of 12.6 years. Egg counts for this selected group were all over 800 eggs per ml of stool with a mean of 1,514 eggs per ml of stool. In children under 15 years of age, the frequency of hepatomegaly and splenomegaly varied directly with the egg count; further, the degree of hepatomegaly was directly correlated with increasing egg counts. No splenic enlargement was noted in children not excreting eggs. In adults, on the other hand, neither splenomegaly nor hepatomegaly could be directly related to schistosomal infection per se. In children, neither the presence of infection with S. mansoni nor its intensity was reflected by altered anthropometric measurements. In the one fazenda tested the frequency of stools positive for occult blood correlated with increasing S. mansoni egg counts.", "contents": "The intensity and effects of infection with Schistosoma mansoni in a rural community in northeast Brazil. The intensity of infection with Schistosoma mansoni and its effects were investigated in a defined population living on three contiguous fazendas (subcounties) in a nonmalarious area of northeast Brazil near Salvador, Bahia. Quantitative stool egg counts (Bell technique) were performed on 363 of 417 individuals (90%) of all ages; physical examinations were done on 294 of 357 individuals (82%) 5 years of age and older. The maximum increase in prevalence was observed between the 1- to 4- and 5- to 9-year age groups, while the maximum increase in fecal egg count occurred between 5- to 9- and 10- to 14-year age groups. Highest egg counts were observed in the 10- to 14-year age group (geometric mean of 301 eggs per ml of stool) while the maximum prevalence (100%) was in the 20- to 24-year age group. In the fazenda with the lowest quantitative egg counts the age specific prevalence rates increased more slowly than in the fazendas with higher egg counts. In the study group nearly 50% of the total fecal egg output was accounted for by 22 individuals (6%) who had a mean age of 12.6 years. Egg counts for this selected group were all over 800 eggs per ml of stool with a mean of 1,514 eggs per ml of stool. In children under 15 years of age, the frequency of hepatomegaly and splenomegaly varied directly with the egg count; further, the degree of hepatomegaly was directly correlated with increasing egg counts. No splenic enlargement was noted in children not excreting eggs. In adults, on the other hand, neither splenomegaly nor hepatomegaly could be directly related to schistosomal infection per se. In children, neither the presence of infection with S. mansoni nor its intensity was reflected by altered anthropometric measurements. In the one fazenda tested the frequency of stools positive for occult blood correlated with increasing S. mansoni egg counts."} {"id": "PMID:1259090", "title": "Echinococcosis in Arizona and New Mexico. Survey of hospital records, 1969-1974.", "content": "In 1974, seven cases of human echinococcosis were diagnosed in Arizona and New Mexico. A retrospective survey of Arizona and New Mexico hospitals obtained data on ten additional cases reported for the 5-year period 1969 through 1973. Sixteen cases were diagnosed as Echinococcus granulosus infections and one as E. multilocularis infection. The latter infection was in an Eskimo from Alaska, where E. multilocularis is endemic. All of the 16 E. granulosus cases were probably acquired autochthonously; 14 were diagnosed in American Indians of the Navajo (8 cases), Zuni (4 cases), and Santo Domingo (2 cases) tribes; the remaining 2 cases were diagnosed in non-Indian women. This is the first published account of echinococcosis autochthonous to Arizona and New Mexico. Evidence suggests that the infection may have been introduced only relatively recently to the areas populated by the American Indians and that parasite transmission to humans is increasing.", "contents": "Echinococcosis in Arizona and New Mexico. Survey of hospital records, 1969-1974. In 1974, seven cases of human echinococcosis were diagnosed in Arizona and New Mexico. A retrospective survey of Arizona and New Mexico hospitals obtained data on ten additional cases reported for the 5-year period 1969 through 1973. Sixteen cases were diagnosed as Echinococcus granulosus infections and one as E. multilocularis infection. The latter infection was in an Eskimo from Alaska, where E. multilocularis is endemic. All of the 16 E. granulosus cases were probably acquired autochthonously; 14 were diagnosed in American Indians of the Navajo (8 cases), Zuni (4 cases), and Santo Domingo (2 cases) tribes; the remaining 2 cases were diagnosed in non-Indian women. This is the first published account of echinococcosis autochthonous to Arizona and New Mexico. Evidence suggests that the infection may have been introduced only relatively recently to the areas populated by the American Indians and that parasite transmission to humans is increasing."} {"id": "PMID:1259091", "title": "Variation among geographic strains of Aedes albopictus in susceptibility to infection with dengue viruses.", "content": "The comparative susceptibility to dengue virus infection of 13 geographic strains of Aedes albopictus was studied by feeding the mosquitoes on a virus-erythrocyte-sugar suspension. Significant variation in susceptibility for each of the four dengue serotypes was observed among the geographic strains. Mosquito strains which were more susceptible to infection with one dengue serotype also were more susceptible to the other dengue serotypes. There was a direct relationship between the amount of virus ingested and the infection rate in a given mosquito strain. A 100-fold difference in oral ID50 was noted between the most and the least susceptible strains. Crossing experiments between susceptible and resistant mosquito strains produced hybrid progeny with intermediate susceptibility. Susceptibility to infection by dengue 2 virus was decreased by selective inbreeding in one strain from 74% to 13% in two generations. Further selection, however, failed to produce a completely resistant line. It appeared that the actual \"barrier\" to infection was in the mosquito midgut.", "contents": "Variation among geographic strains of Aedes albopictus in susceptibility to infection with dengue viruses. The comparative susceptibility to dengue virus infection of 13 geographic strains of Aedes albopictus was studied by feeding the mosquitoes on a virus-erythrocyte-sugar suspension. Significant variation in susceptibility for each of the four dengue serotypes was observed among the geographic strains. Mosquito strains which were more susceptible to infection with one dengue serotype also were more susceptible to the other dengue serotypes. There was a direct relationship between the amount of virus ingested and the infection rate in a given mosquito strain. A 100-fold difference in oral ID50 was noted between the most and the least susceptible strains. Crossing experiments between susceptible and resistant mosquito strains produced hybrid progeny with intermediate susceptibility. Susceptibility to infection by dengue 2 virus was decreased by selective inbreeding in one strain from 74% to 13% in two generations. Further selection, however, failed to produce a completely resistant line. It appeared that the actual \"barrier\" to infection was in the mosquito midgut."} {"id": "PMID:1259092", "title": "Variation among goegraphic strains of Aedes albopictus in susceptibility to infection with chikungunya virus.", "content": "Two types of variation were observed when the susceptibility of 16 different geographic strains of Aedes albopictus to oral infection with chikungunya (CHIK) virus was studied. One was differential susceptibility to infection with the virus. The other was variation in the quantity of virus present in infected mosquitoes after a standard incubation period. Mean virus titers of infected mosquitoes of different geographic strains varied almost 1,000-fold. Attempts to develop increasingly resistant or susceptible mosquito lines through genetic selection were unsuccessful. Infection rates did not change significantly despite 3 to 6 generations of selective inbreeding. In contrast, crosses between strains of high and low CHIK susceptibility yielded hybrid mosquitoes with infection rates and mean virus titers intermediate between those of the parent colonies. These data suggest that at least one factor controlling the susceptibility of A. albopictus to CHIK infection is genetic. Two lines of A. albopictus with a marked difference in susceptibility to oral infection with dengue viruses were equally susceptible to oral infection with chikungunya virus.", "contents": "Variation among goegraphic strains of Aedes albopictus in susceptibility to infection with chikungunya virus. Two types of variation were observed when the susceptibility of 16 different geographic strains of Aedes albopictus to oral infection with chikungunya (CHIK) virus was studied. One was differential susceptibility to infection with the virus. The other was variation in the quantity of virus present in infected mosquitoes after a standard incubation period. Mean virus titers of infected mosquitoes of different geographic strains varied almost 1,000-fold. Attempts to develop increasingly resistant or susceptible mosquito lines through genetic selection were unsuccessful. Infection rates did not change significantly despite 3 to 6 generations of selective inbreeding. In contrast, crosses between strains of high and low CHIK susceptibility yielded hybrid mosquitoes with infection rates and mean virus titers intermediate between those of the parent colonies. These data suggest that at least one factor controlling the susceptibility of A. albopictus to CHIK infection is genetic. Two lines of A. albopictus with a marked difference in susceptibility to oral infection with dengue viruses were equally susceptible to oral infection with chikungunya virus."} {"id": "PMID:1259093", "title": "Vector competence of mosquitoes as a marker to distinguish Central American and Mexican epizootic from enzootic strains of Venezuelan encephalitis virus.", "content": "Two epizootic strains of Venezuelan encephalitis (VE) virus from Central America and Mexico were transmitted by a colonized epizootic vector mosquito, Aedes taeniorhynchus, at higher rates than were two enzootic strains when the mosquitoes were infected by intrathroacic inoculation or feeding of virus. Differences in transmission rates also occurred with colonized Aedes aegypti, but were less marked. Following intrathoracic inoculation of A. taeniorhynchus or A. aegypti, epizootic strains grew to slightly higher concentrations in the mosquitoes than did enzootic strains. Intestinal thresholds of infection for A. taeniorhynchus were slightly lower for epizootic than for enzootic virus strains, but were essentially equal for A. aegypti. Only a small percentage of individual Culex pipiens quinquefasciatus mosquitoes supported growth of epizootic VE virus, and only 1 of 6 tested C. p. quinquefasciatus transmitted virus by bite. Thus, transmission and growth of virus in these Aedes mosquitoes distinguished between these epizootic and enzootic strains of VE virus.", "contents": "Vector competence of mosquitoes as a marker to distinguish Central American and Mexican epizootic from enzootic strains of Venezuelan encephalitis virus. Two epizootic strains of Venezuelan encephalitis (VE) virus from Central America and Mexico were transmitted by a colonized epizootic vector mosquito, Aedes taeniorhynchus, at higher rates than were two enzootic strains when the mosquitoes were infected by intrathroacic inoculation or feeding of virus. Differences in transmission rates also occurred with colonized Aedes aegypti, but were less marked. Following intrathoracic inoculation of A. taeniorhynchus or A. aegypti, epizootic strains grew to slightly higher concentrations in the mosquitoes than did enzootic strains. Intestinal thresholds of infection for A. taeniorhynchus were slightly lower for epizootic than for enzootic virus strains, but were essentially equal for A. aegypti. Only a small percentage of individual Culex pipiens quinquefasciatus mosquitoes supported growth of epizootic VE virus, and only 1 of 6 tested C. p. quinquefasciatus transmitted virus by bite. Thus, transmission and growth of virus in these Aedes mosquitoes distinguished between these epizootic and enzootic strains of VE virus."} {"id": "PMID:1259094", "title": "Plasmodium brasilianum antigen for use in the indirect hemagglutination test.", "content": "Antigen was prepared from Plasmodium brasilianum harvested from an infected spider monkey. This antigen was attached to aldehyde-fixed, human type O cells, and was tested against sera from human cases of P. malaria, P. vivax, P. falciparum, and P. ovale infection, and sera from noninfected persons. At dilutions of 1:16 or greater the antigen failed to react in sera from noninfected persons. It reacted at titers of 16 or above with sera from 85% of the persons with P. malariae infection, 83% with P. vivax infection, 70% with P. falciparum infection, and 70% with P. ovale infection.", "contents": "Plasmodium brasilianum antigen for use in the indirect hemagglutination test. Antigen was prepared from Plasmodium brasilianum harvested from an infected spider monkey. This antigen was attached to aldehyde-fixed, human type O cells, and was tested against sera from human cases of P. malaria, P. vivax, P. falciparum, and P. ovale infection, and sera from noninfected persons. At dilutions of 1:16 or greater the antigen failed to react in sera from noninfected persons. It reacted at titers of 16 or above with sera from 85% of the persons with P. malariae infection, 83% with P. vivax infection, 70% with P. falciparum infection, and 70% with P. ovale infection."} {"id": "PMID:1259096", "title": "Complications of nonoperative extraction of retained common duct stones.", "content": "A morbidity of 5 per cent and no mortality occurred in 612 reported patients undergoing nonoperative extraction of retained common duct stones. Three patients with complications required reoperation, but morbidity and mortality with this new procedure of percutaneous stone removal is significantcantly less than that with operative reexploration of the common duct. The use of small caliber T tubes results in a greater rate of failure and entails more complications. A T tube of no less than number 14 French caliber should be used routinely [2]. Penrose drains should be placed separately from the T tube, and the T tube should be brought out through a lateral stab wound.", "contents": "Complications of nonoperative extraction of retained common duct stones. A morbidity of 5 per cent and no mortality occurred in 612 reported patients undergoing nonoperative extraction of retained common duct stones. Three patients with complications required reoperation, but morbidity and mortality with this new procedure of percutaneous stone removal is significantcantly less than that with operative reexploration of the common duct. The use of small caliber T tubes results in a greater rate of failure and entails more complications. A T tube of no less than number 14 French caliber should be used routinely [2]. Penrose drains should be placed separately from the T tube, and the T tube should be brought out through a lateral stab wound."} {"id": "PMID:1259097", "title": "Nodal response in medullary carcinoma of the breast.", "content": "From 1954 to 1970, ninety-five patients with medullary carcinoma of the breast were evaluated in terms of immunologic activity based on the histologic changes seen within the tumor and regional nodes. Each patient was studied for the degree of lymphocytic infiltration in the tumor as well as the extent of sinus histiocytosis present within the regional nodes. Contrary to what would normally be expected, those nodes with increased sinus histiocytosis were associated with the larger tumors. In addition, lymph node metastasis increased from 26 to 75 per cent as the degree of sinus histiocytosis became more pronounced. There was no evidence that increased lymphocytic infiltration in the tumor resulted in a statistically significant improvement in the five and ten year survival rates. Similarly, sinus histiocytosis activity did not seem to enhance the survival rate among this particular group of patients. There is a suggestion that a correlation exists between sinus histiocytosis and lymphocytic infiltration in the tumor and that, whatever the stimulus present, its effect is on both the lymph node and the degree of lymphocyte response within the tumor. The antigenic substance in the tumor, which initiates the immune response, possibly produces an abortive reaction, which may result in the induction of blocking factors rather then those factors necessary for destruction. It appears that histologic evidence of immunologic enhancement does not necessarily signify improved survival, at least with those patients having carcinoma of the breast.", "contents": "Nodal response in medullary carcinoma of the breast. From 1954 to 1970, ninety-five patients with medullary carcinoma of the breast were evaluated in terms of immunologic activity based on the histologic changes seen within the tumor and regional nodes. Each patient was studied for the degree of lymphocytic infiltration in the tumor as well as the extent of sinus histiocytosis present within the regional nodes. Contrary to what would normally be expected, those nodes with increased sinus histiocytosis were associated with the larger tumors. In addition, lymph node metastasis increased from 26 to 75 per cent as the degree of sinus histiocytosis became more pronounced. There was no evidence that increased lymphocytic infiltration in the tumor resulted in a statistically significant improvement in the five and ten year survival rates. Similarly, sinus histiocytosis activity did not seem to enhance the survival rate among this particular group of patients. There is a suggestion that a correlation exists between sinus histiocytosis and lymphocytic infiltration in the tumor and that, whatever the stimulus present, its effect is on both the lymph node and the degree of lymphocyte response within the tumor. The antigenic substance in the tumor, which initiates the immune response, possibly produces an abortive reaction, which may result in the induction of blocking factors rather then those factors necessary for destruction. It appears that histologic evidence of immunologic enhancement does not necessarily signify improved survival, at least with those patients having carcinoma of the breast."} {"id": "PMID:1259098", "title": "Surgical management of epidermoid carcinoma of the anus.", "content": "An analysis of twenty-six cases of epidermoid carcinoma of the anus from the University of Virginia Medical Center and 1,060 cases from the surgical literature has been presented. We believe this review justifies the following conclusions. (1) Considerable delay in diagnosis frequently occurs, adversely affecting the prognosis of patients with this disease. (2) Abdominoperineal resection remains the treatment of choice. Wide local excision is inadequate for most lesions, and should be reserved for lesions of the anal verge less than 2 cm in diameter with favorable histology, that is, low grade of malignancy. (3) Large lesions and those with a high grade of malignancy are associated with a poor prognosis, but even these patients may sometimes be cured with aggressive surgical excision. (4) Synchronous inguinal node metastases are associated with a poor prognosis, but an occasional patient may be cured by iliofemoral node dissection. (5) Iliofemoral node dissection is indicated for metachronous inguinal node metastases in the absence of distant spread. (6) Iliofemoral node dissection should not be performed if these nodes are not clinically involved with metastases. Approximately 70 per cent of these patients will not need this procedure and would therefore have this resection and its attendant morbidity unnecessarily.", "contents": "Surgical management of epidermoid carcinoma of the anus. An analysis of twenty-six cases of epidermoid carcinoma of the anus from the University of Virginia Medical Center and 1,060 cases from the surgical literature has been presented. We believe this review justifies the following conclusions. (1) Considerable delay in diagnosis frequently occurs, adversely affecting the prognosis of patients with this disease. (2) Abdominoperineal resection remains the treatment of choice. Wide local excision is inadequate for most lesions, and should be reserved for lesions of the anal verge less than 2 cm in diameter with favorable histology, that is, low grade of malignancy. (3) Large lesions and those with a high grade of malignancy are associated with a poor prognosis, but even these patients may sometimes be cured with aggressive surgical excision. (4) Synchronous inguinal node metastases are associated with a poor prognosis, but an occasional patient may be cured by iliofemoral node dissection. (5) Iliofemoral node dissection is indicated for metachronous inguinal node metastases in the absence of distant spread. (6) Iliofemoral node dissection should not be performed if these nodes are not clinically involved with metastases. Approximately 70 per cent of these patients will not need this procedure and would therefore have this resection and its attendant morbidity unnecessarily."} {"id": "PMID:1259099", "title": "Comparison of effect of narcotic and epidural analgesia on postoperative respiratory function.", "content": "A prospective, randomized comparison was made of the value of meperidine versus epidural analgesia when used for the relief of pain after cholecystectomy in twenty patients without cardiopulmonary disease. Respiratory function was assessed the day before surgery and at 3 to 4 hours and 24 hours after operation by the bedside measurement of expiratory peak flow, vital capacity, and arterial blood gases. The two groups of patients were comparable as to age, height, weight, smoking habits, preoperative peak flow, vital capacity, and duration of operation. The arterial oxygen tension and oxygen saturation were significantly greater and carbon dioxide tension lower in the epidural analgesia group 24 hours after operation. At this time peak flow rates and vital capacity were not different. However, at 3 to 4 hours postoperatively, vital capacity was significantly greater in the epidural anesthesia group. This might account for the differences in arterial blood gases the following day. These findings suggest that epidural analgesia is valuable in the early postoperative period after upper abdominal surgery.", "contents": "Comparison of effect of narcotic and epidural analgesia on postoperative respiratory function. A prospective, randomized comparison was made of the value of meperidine versus epidural analgesia when used for the relief of pain after cholecystectomy in twenty patients without cardiopulmonary disease. Respiratory function was assessed the day before surgery and at 3 to 4 hours and 24 hours after operation by the bedside measurement of expiratory peak flow, vital capacity, and arterial blood gases. The two groups of patients were comparable as to age, height, weight, smoking habits, preoperative peak flow, vital capacity, and duration of operation. The arterial oxygen tension and oxygen saturation were significantly greater and carbon dioxide tension lower in the epidural analgesia group 24 hours after operation. At this time peak flow rates and vital capacity were not different. However, at 3 to 4 hours postoperatively, vital capacity was significantly greater in the epidural anesthesia group. This might account for the differences in arterial blood gases the following day. These findings suggest that epidural analgesia is valuable in the early postoperative period after upper abdominal surgery."} {"id": "PMID:1259101", "title": "Operative treatment of appendix mass.", "content": "From January 1972 to March 1974, thirty-four consecutive patients with appendix masses underwent acute appendectomy within 32 hours of admission. There was no death and no morbidity, except local wound problems in six patients and drainage of pus from drain site in four patients. Twenty-four patients were afebrile without wound problems and could be discharged on the seventh postoperative day. Hospital stay ranged from seven to nineteen days with an average of nine days.", "contents": "Operative treatment of appendix mass. From January 1972 to March 1974, thirty-four consecutive patients with appendix masses underwent acute appendectomy within 32 hours of admission. There was no death and no morbidity, except local wound problems in six patients and drainage of pus from drain site in four patients. Twenty-four patients were afebrile without wound problems and could be discharged on the seventh postoperative day. Hospital stay ranged from seven to nineteen days with an average of nine days."} {"id": "PMID:1259102", "title": "Abdominal angina. Intestinal absorption eight years after successful mesenteric revascularization.", "content": "A woman with panmalabsorption and symptoms characteristic of abdominal angina underwent successful revascularization of the superior mesenteric artery. Laboratory studies obtained eight years postoperatively were compared with preoperative data. Her stool fat was reduced to 29 per cent of the preoperative quantity, although her dietary intake of fat was increased fivefold. The d-xylose tolerance test was increased to 346 per cent of the preoperative value, serum carotenes to 817 per cent, serum albumin to 172 per cent, hematocrit to 148 per cent, and cholesterol to 296 per cent. Her weight had risen from 69 to 122 pounds. We conclude that the panmalabsorptive defect associated with mesenteric vascular insufficiency is reversible and that the intestine may function normally for a prolonged period of time after revascularization.", "contents": "Abdominal angina. Intestinal absorption eight years after successful mesenteric revascularization. A woman with panmalabsorption and symptoms characteristic of abdominal angina underwent successful revascularization of the superior mesenteric artery. Laboratory studies obtained eight years postoperatively were compared with preoperative data. Her stool fat was reduced to 29 per cent of the preoperative quantity, although her dietary intake of fat was increased fivefold. The d-xylose tolerance test was increased to 346 per cent of the preoperative value, serum carotenes to 817 per cent, serum albumin to 172 per cent, hematocrit to 148 per cent, and cholesterol to 296 per cent. Her weight had risen from 69 to 122 pounds. We conclude that the panmalabsorptive defect associated with mesenteric vascular insufficiency is reversible and that the intestine may function normally for a prolonged period of time after revascularization."} {"id": "PMID:1259103", "title": "Reoperation for amputation neuroma of the cystic duct.", "content": "Two cases of amputation neuroma of the cystic duct are reported. In both instances, significant symptoms were totally relieved by excision of the neuroma. Review of the literature reveals at least twenty similar cases with the same results. Emphasis is placed on the importance of considering this diagnosis in postcholecystectomy patients after all the usual causes of right upper quadrant symptoms have been ruled out.", "contents": "Reoperation for amputation neuroma of the cystic duct. Two cases of amputation neuroma of the cystic duct are reported. In both instances, significant symptoms were totally relieved by excision of the neuroma. Review of the literature reveals at least twenty similar cases with the same results. Emphasis is placed on the importance of considering this diagnosis in postcholecystectomy patients after all the usual causes of right upper quadrant symptoms have been ruled out."} {"id": "PMID:1259104", "title": "Extremity necrosis caused by indwelling arterial catheters.", "content": "Four patients sustained tissue due to indwelling catheters, three of which were in radial arteries and one of which was in the dorsalis pedis artery, In one of the patients, septic thrombosis was demonstrated. The risk of such complications can be minimized by precannulation evaluation of the arterial circulation of the extremity, by proper care of the catheter when in place, and by careful observation for clinical evidence of infection, ischemia, and other treatable problems.", "contents": "Extremity necrosis caused by indwelling arterial catheters. Four patients sustained tissue due to indwelling catheters, three of which were in radial arteries and one of which was in the dorsalis pedis artery, In one of the patients, septic thrombosis was demonstrated. The risk of such complications can be minimized by precannulation evaluation of the arterial circulation of the extremity, by proper care of the catheter when in place, and by careful observation for clinical evidence of infection, ischemia, and other treatable problems."} {"id": "PMID:1259105", "title": "Hyperparathyroidism: ectopic parathyroid glands.", "content": "A patient with a parathyroid adenoma located beneath the throid capsule and within a benign thyroid adenoma is reported on. To the best of our knowledge, this lesion has not previously been reported. This case points out the difficulties that may be encountered when it is necessary to locate a missing parathyroid gland in a patient with multinocular goiter. In this clinical setting there may be a role for use of the various technics recommended for preoperative localization of a parathyroid adenoma.", "contents": "Hyperparathyroidism: ectopic parathyroid glands. A patient with a parathyroid adenoma located beneath the throid capsule and within a benign thyroid adenoma is reported on. To the best of our knowledge, this lesion has not previously been reported. This case points out the difficulties that may be encountered when it is necessary to locate a missing parathyroid gland in a patient with multinocular goiter. In this clinical setting there may be a role for use of the various technics recommended for preoperative localization of a parathyroid adenoma."} {"id": "PMID:1259106", "title": "Neck mass caused by thrombus in the external jugular vein.", "content": "Three cases of lateral neck tumors caused by thrombosis of the external jugular vein have been presented. Microscopic examination of the excised thrombosed veins revealed all of them to have a dilated architecture with somewhat degenerated vessel walls much like an aneurysm. Such a dilatation would cause some stasis and eddy currents and make the vessels more susceptible to thrombus formation. The final factor which induced these thrombi remains unknown. Indeed, when the interrelation of the factors discussed previously is considered, multiple etiologic factors appear most likely. Some form of minor trauma, although not documented, would still seem the most likely cause of thrombosis of a vein in a patient with no previous symptoms. In case III, trauma of inflammatory changes in a mass already noted to be present for some time could have induced thrombosis within the dilated vessel. Thrombosis of the external jugular vein is yet another lesion in the extensive differential diagnosis of a mass in the lateral neck.", "contents": "Neck mass caused by thrombus in the external jugular vein. Three cases of lateral neck tumors caused by thrombosis of the external jugular vein have been presented. Microscopic examination of the excised thrombosed veins revealed all of them to have a dilated architecture with somewhat degenerated vessel walls much like an aneurysm. Such a dilatation would cause some stasis and eddy currents and make the vessels more susceptible to thrombus formation. The final factor which induced these thrombi remains unknown. Indeed, when the interrelation of the factors discussed previously is considered, multiple etiologic factors appear most likely. Some form of minor trauma, although not documented, would still seem the most likely cause of thrombosis of a vein in a patient with no previous symptoms. In case III, trauma of inflammatory changes in a mass already noted to be present for some time could have induced thrombosis within the dilated vessel. Thrombosis of the external jugular vein is yet another lesion in the extensive differential diagnosis of a mass in the lateral neck."} {"id": "PMID:1259107", "title": "A suture-tightening technic for delayed wound closure.", "content": "A method is described that allows the tightening of standard suture materials for skin approximation of open wounds. The need for wire sutures in such circumstances is therefore unnecessary. The technic has been applied in delayed primary or secondary wound closure, and in the tightening of loosened ties or retention sutures.", "contents": "A suture-tightening technic for delayed wound closure. A method is described that allows the tightening of standard suture materials for skin approximation of open wounds. The need for wire sutures in such circumstances is therefore unnecessary. The technic has been applied in delayed primary or secondary wound closure, and in the tightening of loosened ties or retention sutures."} {"id": "PMID:1259108", "title": "A technic for restoring intestinal continuity after left hemicolectomy for cancer of the distal colon and rectum.", "content": "Retroileal retroperitoneal transplantation of the transverse colon allows additional length for safe colorectostomy after left hemicolectomy in patients with short proximal colonic remnants.", "contents": "A technic for restoring intestinal continuity after left hemicolectomy for cancer of the distal colon and rectum. Retroileal retroperitoneal transplantation of the transverse colon allows additional length for safe colorectostomy after left hemicolectomy in patients with short proximal colonic remnants."} {"id": "PMID:1259109", "title": "Sliding lock modification of standard tissue forceps.", "content": "This report describes a modification of the standard thumb forceps to provide a simple locking mechanism. This increases its usefulness in many surgical procedures. Certain advantages are presented and the instrument is illustrated and described.", "contents": "Sliding lock modification of standard tissue forceps. This report describes a modification of the standard thumb forceps to provide a simple locking mechanism. This increases its usefulness in many surgical procedures. Certain advantages are presented and the instrument is illustrated and described."} {"id": "PMID:1259110", "title": "A constant pressure infusor.", "content": "A device for maintaining a constant pressure in a pressure infusor is described.", "contents": "A constant pressure infusor. A device for maintaining a constant pressure in a pressure infusor is described."} {"id": "PMID:1259120", "title": "Ketamine and the oculocardiac reflex. Dysrhythmia in pediatric strabismus surgery: the role of intravenous atropine.", "content": "Fifty children in the age-group 1.75-10 years, admitted for cure of strabismus, were anaesthetised with intramuscular ketamine. Half the patients, at random, were given intravenous atropine, while anaesthetised, 5 minutes before operative interference. ECG recording of Lead 2 showed an oculacardiac dysthythmic response to muscle pull in 19 of the 25 unatropinised patients. The atropinised patients failed to show evidence of muscle induced dysrhythmia in any of the subjects (0%) The 25 control traces in the atropinised subjects showed no dysrhythmia after 5 minutes, but the possible immediate transitory dysrhythmic effects of atropine in the presence of ketamine anaesthesia is the subject of further study.", "contents": "Ketamine and the oculocardiac reflex. Dysrhythmia in pediatric strabismus surgery: the role of intravenous atropine. Fifty children in the age-group 1.75-10 years, admitted for cure of strabismus, were anaesthetised with intramuscular ketamine. Half the patients, at random, were given intravenous atropine, while anaesthetised, 5 minutes before operative interference. ECG recording of Lead 2 showed an oculacardiac dysthythmic response to muscle pull in 19 of the 25 unatropinised patients. The atropinised patients failed to show evidence of muscle induced dysrhythmia in any of the subjects (0%) The 25 control traces in the atropinised subjects showed no dysrhythmia after 5 minutes, but the possible immediate transitory dysrhythmic effects of atropine in the presence of ketamine anaesthesia is the subject of further study."} {"id": "PMID:1259126", "title": "[The effect of Fentanyl and Althesin on haemodynamics, inotropism of the heart and myocardial oxygen consumption in man (author's transl)].", "content": "The acute effect of Fentanyl and Althesin upon haemodynamics, inotropism of the heart and myocardial oxygen consumption has not been studied in man so far. Healthy premedicated pateints (n = 16) were lightly anaesthetized with nitrous oxide-oxygen (ratio 2:1), 0.3 Vol.-% forane and 0.3 Vol.-% halothane respectively. In order to avoid any interference with respiratory depression all subjects were normoventilated via an orotracheal tube. In a circulatory steady state a single dose of 0.01 mg/kg Fentanyl (n = 7) and 0.075 mg/kg Althesin (n = 9) respectively was injected intravenously within 20 sec. After the application of Fentanyl there was a delayed (5th min) fall in blood pressure by 23%, which was due to a reduction in total peripheral resistance (12%) and in cardiac output (thermodilution technique) by 13%. The decrease in cardiac output was the result of a bradycardia (18%). Considering heart rate, pre- and afterload simultaneously, the fall in max dp/dt (catheter-tip manometer) by 20% could not be explained as a decrease in myocardial contractility. The altered haemodynamics led to a decrease of the myocardial oxygen consumption (control 6.4 ml O2/min x 100 g) by 31%. The energy demand of the heart was quantitatively calculated using the formula of the complex haemodynamic parameter developed by Bretschneider. Immediately after the administration of Althesin the cardiac output rose on account of tachycardia slightly, while stroke volume (19%), total peripheral resistance (32%) and mean arterial pressure (24%) reacted reversely. Since heart rate increased (11%), preload remainded unchanged and afterload decreased, the fall in dp/dt max (20%) has to be understood as a moderate reduction in myocardial inotropism. The energy demand of the heart decreased only initially by 15%. The clinical implications of the results were discussed.", "contents": "[The effect of Fentanyl and Althesin on haemodynamics, inotropism of the heart and myocardial oxygen consumption in man (author's transl)]. The acute effect of Fentanyl and Althesin upon haemodynamics, inotropism of the heart and myocardial oxygen consumption has not been studied in man so far. Healthy premedicated pateints (n = 16) were lightly anaesthetized with nitrous oxide-oxygen (ratio 2:1), 0.3 Vol.-% forane and 0.3 Vol.-% halothane respectively. In order to avoid any interference with respiratory depression all subjects were normoventilated via an orotracheal tube. In a circulatory steady state a single dose of 0.01 mg/kg Fentanyl (n = 7) and 0.075 mg/kg Althesin (n = 9) respectively was injected intravenously within 20 sec. After the application of Fentanyl there was a delayed (5th min) fall in blood pressure by 23%, which was due to a reduction in total peripheral resistance (12%) and in cardiac output (thermodilution technique) by 13%. The decrease in cardiac output was the result of a bradycardia (18%). Considering heart rate, pre- and afterload simultaneously, the fall in max dp/dt (catheter-tip manometer) by 20% could not be explained as a decrease in myocardial contractility. The altered haemodynamics led to a decrease of the myocardial oxygen consumption (control 6.4 ml O2/min x 100 g) by 31%. The energy demand of the heart was quantitatively calculated using the formula of the complex haemodynamic parameter developed by Bretschneider. Immediately after the administration of Althesin the cardiac output rose on account of tachycardia slightly, while stroke volume (19%), total peripheral resistance (32%) and mean arterial pressure (24%) reacted reversely. Since heart rate increased (11%), preload remainded unchanged and afterload decreased, the fall in dp/dt max (20%) has to be understood as a moderate reduction in myocardial inotropism. The energy demand of the heart decreased only initially by 15%. The clinical implications of the results were discussed."} {"id": "PMID:1259127", "title": "[The effects of sodiumnitroprusside and trimethaphan induced hypotension on haemodynamics and myocardial oxygen consumption (author's transl)].", "content": "The influence of controlled hypotension (mean arterial pressure 60 mmHg) induced by sodium nitroprusside and trimethaphan on systemic circulation and myocardial oxygen consumption was studied in 7 anaesthetized closed chest dogs. The hypotensive effect of both drugs was primarily mediated by a reduction in total peripheral resistance. No change in cardiac output was observed. Stroke volume decreased in the presence of tachycardia. Left ventricular max dp/dt remained unaffected during sodium nitroprusside hypotension and was reduced by trimethaphan. Max dp/dt, load data and heart rate indicated that trimetaphan possesses negative inotropic properties. Sodium nitroprusside induced a hyperperfusion of the heart with a marked decrease in myocardial arteriovenous difference in oxygen. Myocardial oxygen consumption remained unchanged. Trimethaphan, on the other hand, induced only small increments in coronary blood flow and a rise in the arteriovenous difference in oxygen of the heart. This resulted in a higher myocardial oxygen consumption (+16%). Cardiac efficiency was lessened by trimethaphan and remained unaffected in the presence of sodium nitroprusside. As sodium nitroprusside neither affects myocardial oxygen consumption nor alters myocardial contractility, we conclude that sodium nitroprusside has advantages over trimethaphan in the management of controlled hypotension and in the therapy of hypertensive crisis and cardiogenic shock.", "contents": "[The effects of sodiumnitroprusside and trimethaphan induced hypotension on haemodynamics and myocardial oxygen consumption (author's transl)]. The influence of controlled hypotension (mean arterial pressure 60 mmHg) induced by sodium nitroprusside and trimethaphan on systemic circulation and myocardial oxygen consumption was studied in 7 anaesthetized closed chest dogs. The hypotensive effect of both drugs was primarily mediated by a reduction in total peripheral resistance. No change in cardiac output was observed. Stroke volume decreased in the presence of tachycardia. Left ventricular max dp/dt remained unaffected during sodium nitroprusside hypotension and was reduced by trimethaphan. Max dp/dt, load data and heart rate indicated that trimetaphan possesses negative inotropic properties. Sodium nitroprusside induced a hyperperfusion of the heart with a marked decrease in myocardial arteriovenous difference in oxygen. Myocardial oxygen consumption remained unchanged. Trimethaphan, on the other hand, induced only small increments in coronary blood flow and a rise in the arteriovenous difference in oxygen of the heart. This resulted in a higher myocardial oxygen consumption (+16%). Cardiac efficiency was lessened by trimethaphan and remained unaffected in the presence of sodium nitroprusside. As sodium nitroprusside neither affects myocardial oxygen consumption nor alters myocardial contractility, we conclude that sodium nitroprusside has advantages over trimethaphan in the management of controlled hypotension and in the therapy of hypertensive crisis and cardiogenic shock."} {"id": "PMID:1259128", "title": "Nephrotoxic effect of methoxyflurane anesthesia. A case report.", "content": "A patient with normal preoperative hepatic and renal laboratory findings was exposed to relatively low concentrations of methoxyflurane during a routine anaesthetic procedure. For at least 12 postoperative days, the patient showed unusually high level of inorganic serum fluoride; his urinary excretion of fluoride and oxalic acid were also increased. However, he had no clinical signs of nephrotoxicity. This observation suggests that some patients with presumably normal renal function may have a low threshhold for the nephrotoxic effects of methoxyflurane.", "contents": "Nephrotoxic effect of methoxyflurane anesthesia. A case report. A patient with normal preoperative hepatic and renal laboratory findings was exposed to relatively low concentrations of methoxyflurane during a routine anaesthetic procedure. For at least 12 postoperative days, the patient showed unusually high level of inorganic serum fluoride; his urinary excretion of fluoride and oxalic acid were also increased. However, he had no clinical signs of nephrotoxicity. This observation suggests that some patients with presumably normal renal function may have a low threshhold for the nephrotoxic effects of methoxyflurane."} {"id": "PMID:1259131", "title": "[Reduction of apparatus deadspace in pediatric anaesthesia (author's transl)].", "content": "The size of inhalation equipment deadspace in infant anaesthesia is of critical importance. While endotracheal intubation reduces anatomical deadspace, the added deadspace of the tube connector tends to increase the overall deadspace by 6 to 10 ml. In order to ensure optimal gas exchange at minimal respiratory effort a new tube was designed which separates inspiratory gas down to the level of the vocal cords and maintains rapid gas flow by a Venturi injector. In controlled air ventilation this tube improves arterial pO2 by 15% and reduces tidal-volume 35% compared to Magill tubes of equal size.", "contents": "[Reduction of apparatus deadspace in pediatric anaesthesia (author's transl)]. The size of inhalation equipment deadspace in infant anaesthesia is of critical importance. While endotracheal intubation reduces anatomical deadspace, the added deadspace of the tube connector tends to increase the overall deadspace by 6 to 10 ml. In order to ensure optimal gas exchange at minimal respiratory effort a new tube was designed which separates inspiratory gas down to the level of the vocal cords and maintains rapid gas flow by a Venturi injector. In controlled air ventilation this tube improves arterial pO2 by 15% and reduces tidal-volume 35% compared to Magill tubes of equal size."} {"id": "PMID:1259124", "title": "The temperture inside carbon dioxide absorbers.", "content": "The temperature changes which occur when soda lime is used to absorb carbon dioxide were measured simulated clinical conditions. The temperature reached in the circle absorption system was found to vary with the room temperature; with a room temperature of 24 degrees C, all brands of soda lime tested reached 40 degrees C in the centre of the circle system. The 'to and fro' absorber achieved a central temperature approximately 5 degrees C higher than in the circle absorber. Temperatures at the periphery were always lower than those measured at the centre of the system. It is still advisable to avoid the use of trichloroethylene in the presence of soda lime and the absence of a safety lock on new anaesthetic machines is regrettable.", "contents": "The temperture inside carbon dioxide absorbers. The temperature changes which occur when soda lime is used to absorb carbon dioxide were measured simulated clinical conditions. The temperature reached in the circle absorption system was found to vary with the room temperature; with a room temperature of 24 degrees C, all brands of soda lime tested reached 40 degrees C in the centre of the circle system. The 'to and fro' absorber achieved a central temperature approximately 5 degrees C higher than in the circle absorber. Temperatures at the periphery were always lower than those measured at the centre of the system. It is still advisable to avoid the use of trichloroethylene in the presence of soda lime and the absence of a safety lock on new anaesthetic machines is regrettable."} {"id": "PMID:1259132", "title": "[Suxamethonium-induced hyperkalaemia in patients with severe intraabdominal infections (author's transl)].", "content": "A serious danger to the circulation following the administration of suxamethonium is known to occur in patients reacting with an abnormal release of potassium. So far the following groups of patients have been found to be at an increased risk: burns, multiple trauma, tetanus, neurological disorders, uraemia. As a result of our investigations patients with severe intraabdominal infections are also to be regarded as at risk. Four of ten patients with this diagnosis have shown an increase of serum-potassium of more than 2.5 mequiv/l following suxamethonium injection in spite of a prophylactic small dose of nondepolarizing relaxant. The predisposing factors are high fever of over a week's duration and a leucocytosis of more than 10,000/cu. mm. A possible hypothesis and pathogenesis of the abnormal efflux of potassium is discussed. Prophylaxis consists of using only nondepolarizing relaxants in these cases. When there is a special indication for suxamethonium the potassium increase can be lessened if the patient is given a small dose of nondepolarizing relaxant prior to the administration of suxamethonium.", "contents": "[Suxamethonium-induced hyperkalaemia in patients with severe intraabdominal infections (author's transl)]. A serious danger to the circulation following the administration of suxamethonium is known to occur in patients reacting with an abnormal release of potassium. So far the following groups of patients have been found to be at an increased risk: burns, multiple trauma, tetanus, neurological disorders, uraemia. As a result of our investigations patients with severe intraabdominal infections are also to be regarded as at risk. Four of ten patients with this diagnosis have shown an increase of serum-potassium of more than 2.5 mequiv/l following suxamethonium injection in spite of a prophylactic small dose of nondepolarizing relaxant. The predisposing factors are high fever of over a week's duration and a leucocytosis of more than 10,000/cu. mm. A possible hypothesis and pathogenesis of the abnormal efflux of potassium is discussed. Prophylaxis consists of using only nondepolarizing relaxants in these cases. When there is a special indication for suxamethonium the potassium increase can be lessened if the patient is given a small dose of nondepolarizing relaxant prior to the administration of suxamethonium."} {"id": "PMID:1259121", "title": "Adsorption of anaesthetic vapours on charcoal beds.", "content": "The adsorptive properties of four charcoals have been examined in relation to their value as adsorbents in filters attached to an anaesthetic trolley. Data for four anaesthetics have been obtained. The test conditions (flow rate, concentration, humidity) were those relevant to the application, and the effect of variation of these conditions was also studied. The air flow resistance of the charcoals was measured. Basic data are thus provided for the design of suitable adsorbers. The performance of two prototype anaesthetic adsorbers has been measured.", "contents": "Adsorption of anaesthetic vapours on charcoal beds. The adsorptive properties of four charcoals have been examined in relation to their value as adsorbents in filters attached to an anaesthetic trolley. Data for four anaesthetics have been obtained. The test conditions (flow rate, concentration, humidity) were those relevant to the application, and the effect of variation of these conditions was also studied. The air flow resistance of the charcoals was measured. Basic data are thus provided for the design of suitable adsorbers. The performance of two prototype anaesthetic adsorbers has been measured."} {"id": "PMID:1259123", "title": "Effects of sodium nitroprusside during the excision of phaeochromocytoma.", "content": "A case report is presented which illustrates the use of sodium nitroprusside to control blood pressure levels during neurolept anaesthetic technique for removal of phaeochromocytoma. In this case the evanescent action of nitroprusside was advantageous since when the drug was discontinued elevation of blood pressure gave rise to suspicion that further catecholamine-secreting tumour was present. In all, four such tumours were removed from this patient.", "contents": "Effects of sodium nitroprusside during the excision of phaeochromocytoma. A case report is presented which illustrates the use of sodium nitroprusside to control blood pressure levels during neurolept anaesthetic technique for removal of phaeochromocytoma. In this case the evanescent action of nitroprusside was advantageous since when the drug was discontinued elevation of blood pressure gave rise to suspicion that further catecholamine-secreting tumour was present. In all, four such tumours were removed from this patient."} {"id": "PMID:1259179", "title": "Circadian rhythm in DNA synthesis in mouse thymus: effect of altered lighting regimens, restricted feeding and presence of Ehrlich ascites tumor.", "content": "A circadian rhythm in the incorporation of tritiated thymidine into DNA of the mouse thymus has been described. This same rhythm in animals bearing an 8-day Ehrlich ascites tumor (EAT) was altered in its phasing, wave-form and over-all 24-hour mean; the most striking alteration seen in four out of five studies was a reduction in the over-all DNA synthesis rate in tumor-bearing animals. Mice subjected to an altered light-dark cycle did not show a complete phase shift in their thymus DNA rhythm within two weeks, but during this time the rhythm in the mitotic index of their corneal epithelium completely phase shifted; the presence of the tumor had no effect on this latter rhythm. In mice subjected to a daily 4-hour restricted feeding schedule, the rhythm in DNA synthesis in the thymus became synchronized in that the peak occurred toward the end of the 4-hour restricted feeding span in both tumor and non-tumor-bearing animals. The rhythm in the mitotic index in the cornea was not phase shifted or altered by the restricted meal timing. The DNA synthesis rhythm in the normal thymus demonstrated a phasing similar to (1) the rhythm in the length of survival time in untreated mice challenged with EAT and (2) the rhythm in DNA synthesis in the normal spleen.", "contents": "Circadian rhythm in DNA synthesis in mouse thymus: effect of altered lighting regimens, restricted feeding and presence of Ehrlich ascites tumor. A circadian rhythm in the incorporation of tritiated thymidine into DNA of the mouse thymus has been described. This same rhythm in animals bearing an 8-day Ehrlich ascites tumor (EAT) was altered in its phasing, wave-form and over-all 24-hour mean; the most striking alteration seen in four out of five studies was a reduction in the over-all DNA synthesis rate in tumor-bearing animals. Mice subjected to an altered light-dark cycle did not show a complete phase shift in their thymus DNA rhythm within two weeks, but during this time the rhythm in the mitotic index of their corneal epithelium completely phase shifted; the presence of the tumor had no effect on this latter rhythm. In mice subjected to a daily 4-hour restricted feeding schedule, the rhythm in DNA synthesis in the thymus became synchronized in that the peak occurred toward the end of the 4-hour restricted feeding span in both tumor and non-tumor-bearing animals. The rhythm in the mitotic index in the cornea was not phase shifted or altered by the restricted meal timing. The DNA synthesis rhythm in the normal thymus demonstrated a phasing similar to (1) the rhythm in the length of survival time in untreated mice challenged with EAT and (2) the rhythm in DNA synthesis in the normal spleen."} {"id": "PMID:1259180", "title": "Cell differentiation in the terminal tubule of fetal rat submandibular gland in organ culture.", "content": "Submandibular glands from 17-day-old rat fetuses were maintained in organ culture for five days in a medium consisting of Eagle's MEM (87%), horse serum (10%), and chick embryo extract (3%). Each day of the culture period explants were incubated for the demonstration of peroxidase activity and processed for light and electron microscopic observations. In some experiments cultures were exposed to 3H-thymidine one hour prior to fixation and incubation for the demonstration of peroxidase activity. Labelling index was determined using radioautographs of 1 mu Epon-embedded sections. At the time of explantation the submandibular gland rudiment consisted of undifferentiated epithelial cells arranged in cords. On day 3 of culture two additional cell types could be distinguished: terminal tubule cells and proacinar cells. The proacinar cells were characterized by peroxidase activity in their granules and cytoplasm. By day 4 acinar cells begin to appear. On the fifth day of culture the four cell types of the terminal tubule were present in the following proportions: undifferentiated cells, 44%; terminal tubule cells, 19%; proacinar cells, 31%; acinar cells, 6%. These results indicate that the cytodifferentiation of the secretory unit of rat submandibular gland in vitro is comparable to the differentiation in vivo.", "contents": "Cell differentiation in the terminal tubule of fetal rat submandibular gland in organ culture. Submandibular glands from 17-day-old rat fetuses were maintained in organ culture for five days in a medium consisting of Eagle's MEM (87%), horse serum (10%), and chick embryo extract (3%). Each day of the culture period explants were incubated for the demonstration of peroxidase activity and processed for light and electron microscopic observations. In some experiments cultures were exposed to 3H-thymidine one hour prior to fixation and incubation for the demonstration of peroxidase activity. Labelling index was determined using radioautographs of 1 mu Epon-embedded sections. At the time of explantation the submandibular gland rudiment consisted of undifferentiated epithelial cells arranged in cords. On day 3 of culture two additional cell types could be distinguished: terminal tubule cells and proacinar cells. The proacinar cells were characterized by peroxidase activity in their granules and cytoplasm. By day 4 acinar cells begin to appear. On the fifth day of culture the four cell types of the terminal tubule were present in the following proportions: undifferentiated cells, 44%; terminal tubule cells, 19%; proacinar cells, 31%; acinar cells, 6%. These results indicate that the cytodifferentiation of the secretory unit of rat submandibular gland in vitro is comparable to the differentiation in vivo."} {"id": "PMID:1259181", "title": "Quantitation of ultrastructural changes in the mouse pineal in response to continuous illumination.", "content": "Adult male mice were exposed to either alternating illumination or constant illumination for 70 days. Light and dark pinealocytes were compared as to distribution within the gland and ultrastructure. Quantitative studies with the electron microscope revealed a significant reduction in pinealocyte size and Golgi complex size in constant light treatment, as well as a marked but nonsignificant reduction in the concentration of lipid droplets and irregular vacuoles. Under constant light treatment the cross-sectional area of pinealocyte pericapillary terminals and the number of granulated vesicles per terminal decreased significantly. A greater number of mitochondria appeared swollen, with rarified matrix and reduced numbers of cristae, with constant light treatment. These results provide ultrastructural correlation with the known reduction of pineal weight, protein synthesis and antigonadotrophic activity that is seen with constant light treatment. The marked decrease in concentration of pinealocyte granulated vesicles in constant light treatment gives morphological support to the theory that these vesicles contain antigonadotrophic secretory material.", "contents": "Quantitation of ultrastructural changes in the mouse pineal in response to continuous illumination. Adult male mice were exposed to either alternating illumination or constant illumination for 70 days. Light and dark pinealocytes were compared as to distribution within the gland and ultrastructure. Quantitative studies with the electron microscope revealed a significant reduction in pinealocyte size and Golgi complex size in constant light treatment, as well as a marked but nonsignificant reduction in the concentration of lipid droplets and irregular vacuoles. Under constant light treatment the cross-sectional area of pinealocyte pericapillary terminals and the number of granulated vesicles per terminal decreased significantly. A greater number of mitochondria appeared swollen, with rarified matrix and reduced numbers of cristae, with constant light treatment. These results provide ultrastructural correlation with the known reduction of pineal weight, protein synthesis and antigonadotrophic activity that is seen with constant light treatment. The marked decrease in concentration of pinealocyte granulated vesicles in constant light treatment gives morphological support to the theory that these vesicles contain antigonadotrophic secretory material."} {"id": "PMID:1259182", "title": "A freeze-fracture study of sarcoplasmic reticulum from fast and slow muscle of the mouse.", "content": "Sarcoplasmic reticulum (SR) of fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles of the mouse was examined by freeze-fracture techniques. A distinctive feature of sarcoplasmic reticulum from the EDL is the presence of hillocks on the A-face within the terminal cisterns. These hillocks are usually arranged in a single row which is deployed parallel to the long axis of the adjacent T-tubule. Center-to-center spacing of hillocks within a row is about 70-75 nm. Hillocks are also found scattered within the collar region. The EDL of ten week mice was characterized by sheet-like terminal and intermediate cisterns, the latter being replaced in 37 week animals by thin tubular longitudinal elements of the SR which contain no hillocks or dimples. Hillocks occur only occasionally in SR from 10 or 20 week SOL muscle. In such cases the hillocks occur singly rather than in rows as in the terminal cisterns of EDL. The predominant form of SR in the SOL contains no hillocks. Total particles in the A-face of EDL-SR (2996 particles/mu2; S.D. = +/- 287) slightly exceeded that of SOL-SR (2558 particles/mu2; S.D. = 274 8 NM). Packing density of 8 nm particles was slightly higher for EDL (750/mu2) VS. SOL (700/mu2). The possible significance of these features of SR in fast and slow muscle is discussed.", "contents": "A freeze-fracture study of sarcoplasmic reticulum from fast and slow muscle of the mouse. Sarcoplasmic reticulum (SR) of fast extensor digitorum longus (EDL) and slow soleus (SOL) muscles of the mouse was examined by freeze-fracture techniques. A distinctive feature of sarcoplasmic reticulum from the EDL is the presence of hillocks on the A-face within the terminal cisterns. These hillocks are usually arranged in a single row which is deployed parallel to the long axis of the adjacent T-tubule. Center-to-center spacing of hillocks within a row is about 70-75 nm. Hillocks are also found scattered within the collar region. The EDL of ten week mice was characterized by sheet-like terminal and intermediate cisterns, the latter being replaced in 37 week animals by thin tubular longitudinal elements of the SR which contain no hillocks or dimples. Hillocks occur only occasionally in SR from 10 or 20 week SOL muscle. In such cases the hillocks occur singly rather than in rows as in the terminal cisterns of EDL. The predominant form of SR in the SOL contains no hillocks. Total particles in the A-face of EDL-SR (2996 particles/mu2; S.D. = +/- 287) slightly exceeded that of SOL-SR (2558 particles/mu2; S.D. = 274 8 NM). Packing density of 8 nm particles was slightly higher for EDL (750/mu2) VS. SOL (700/mu2). The possible significance of these features of SR in fast and slow muscle is discussed."} {"id": "PMID:1259183", "title": "Folliculogenesis in the ovary of the mature mouse: a radioautographic study.", "content": "Studies on the growth sequence of follicles in mature mice four to six months old were conducted by giving the three injections of 16 muCi tritiated thymidine (3H-T)/gm body weight at four hour intervals over a period of eight hours. Subsequent radioautographic analysis on ovaries obtaine d 1,3,5,9, and 17 days after the last injection showed an overall follicle growth time of 17 to 19 days. The duration of the different follicle stage times were also estimated from radioautographic data. Intense 3H-T incorporation was noted in the developing antra and zona pellucida of follicles of animals sarcrificed on e and three days after treatment suggesting that these areas serve as precursor storage sites during development. Oocytes of follicles in early antrum formation also showed juxtanucleolar 3H-T incorporation concomitantly with rapid and massive oocyte and follicular growth. The findings further indicate that the earliest follicular cells surrounding the oocyte originate at some distance from the developing primordial follicle.", "contents": "Folliculogenesis in the ovary of the mature mouse: a radioautographic study. Studies on the growth sequence of follicles in mature mice four to six months old were conducted by giving the three injections of 16 muCi tritiated thymidine (3H-T)/gm body weight at four hour intervals over a period of eight hours. Subsequent radioautographic analysis on ovaries obtaine d 1,3,5,9, and 17 days after the last injection showed an overall follicle growth time of 17 to 19 days. The duration of the different follicle stage times were also estimated from radioautographic data. Intense 3H-T incorporation was noted in the developing antra and zona pellucida of follicles of animals sarcrificed on e and three days after treatment suggesting that these areas serve as precursor storage sites during development. Oocytes of follicles in early antrum formation also showed juxtanucleolar 3H-T incorporation concomitantly with rapid and massive oocyte and follicular growth. The findings further indicate that the earliest follicular cells surrounding the oocyte originate at some distance from the developing primordial follicle."} {"id": "PMID:1259184", "title": "Dobutamine for inotropic support during emergence from cardiopulmonary bypass.", "content": "Dobutamine, a recently introduced derivative of dopamine, is reported to retain inotropic properties with less pronounced chronotropic and arrhythmogenic effects than isoproterenol. The drug was evaluated in two doses, 5 mug/kg/min and 10 mug/kg/min, in two groups of ten patients each, during emergence from cardiopulmonary bypass. A third group of five patients was studied similarly with isoproterenol, 0.02 mug/kg/min. Cardiac index increased 16 and 28 per cent eith the two doses of dobutamine, respectively, and 9 per cent with isoproterenol. Heart rate, in contrast, increased 6 and 15 per cent with dobutamine (not significant) and 44 per cent with isoproterenol (significant). Dobutamine seemed to associated with fewer arrhythmias than isoproterenol. It is concluded that dobutamine, 5-10 mug/kg/min, is suitable for use during emergence from cardiopulmonary bypass and may possess advantages over isoproterenol.", "contents": "Dobutamine for inotropic support during emergence from cardiopulmonary bypass. Dobutamine, a recently introduced derivative of dopamine, is reported to retain inotropic properties with less pronounced chronotropic and arrhythmogenic effects than isoproterenol. The drug was evaluated in two doses, 5 mug/kg/min and 10 mug/kg/min, in two groups of ten patients each, during emergence from cardiopulmonary bypass. A third group of five patients was studied similarly with isoproterenol, 0.02 mug/kg/min. Cardiac index increased 16 and 28 per cent eith the two doses of dobutamine, respectively, and 9 per cent with isoproterenol. Heart rate, in contrast, increased 6 and 15 per cent with dobutamine (not significant) and 44 per cent with isoproterenol (significant). Dobutamine seemed to associated with fewer arrhythmias than isoproterenol. It is concluded that dobutamine, 5-10 mug/kg/min, is suitable for use during emergence from cardiopulmonary bypass and may possess advantages over isoproterenol."} {"id": "PMID:1259185", "title": "Microbial flora of the larynx, trachea, and large intestine of the rat after long-term inhalation of 100 per cent oxygen.", "content": "Effects of long-term inhalation of 100 per cent oxygen on the microbial flora of the rat larynx, trachea, and large intestine were studies. Rats were kept 14 days in an atmosphere of 100 per cent oxygen after being conditioned to high oxygen concentrations by exposure to three cycles of 100 per cent oxygen (two days) alternating with 40 percent oxygen (two days). Controls were kept under similar conditions in normal atmosphere. Rats were sacrificed, and at necropsy laryngotracheal swabs and fecal material from the large intestine were obtained and cultured for bacteria and fungi. Streptobacillus moniliformis, the predominant microorganism in the upper tracheas of controls, was not isolated from the oxygen-treated rats. Alpha-hemolytic streptococcus and Staphylococcus albus were present in control rats, but were found less frequently in rats exposed to oxygen. Pseudomonas and Proteus, infrequently isolated from controls, were predominant and sometimes the only microorganisms isolated from oxygen-treated rats. The data indicate that prolonged exposure of the rat to 100 per cent oxygen shifts the microbial flora in the upper respiratory tract from mainly gram-positive to mainly gram-negative bacteria. In contrast, there was no significant difference between the microbial flora in large intestines of control and oxygen-treated rats. The possibility that similar changes may occur in man should be considered when prolonged oxygen therapy is contemplated.", "contents": "Microbial flora of the larynx, trachea, and large intestine of the rat after long-term inhalation of 100 per cent oxygen. Effects of long-term inhalation of 100 per cent oxygen on the microbial flora of the rat larynx, trachea, and large intestine were studies. Rats were kept 14 days in an atmosphere of 100 per cent oxygen after being conditioned to high oxygen concentrations by exposure to three cycles of 100 per cent oxygen (two days) alternating with 40 percent oxygen (two days). Controls were kept under similar conditions in normal atmosphere. Rats were sacrificed, and at necropsy laryngotracheal swabs and fecal material from the large intestine were obtained and cultured for bacteria and fungi. Streptobacillus moniliformis, the predominant microorganism in the upper tracheas of controls, was not isolated from the oxygen-treated rats. Alpha-hemolytic streptococcus and Staphylococcus albus were present in control rats, but were found less frequently in rats exposed to oxygen. Pseudomonas and Proteus, infrequently isolated from controls, were predominant and sometimes the only microorganisms isolated from oxygen-treated rats. The data indicate that prolonged exposure of the rat to 100 per cent oxygen shifts the microbial flora in the upper respiratory tract from mainly gram-positive to mainly gram-negative bacteria. In contrast, there was no significant difference between the microbial flora in large intestines of control and oxygen-treated rats. The possibility that similar changes may occur in man should be considered when prolonged oxygen therapy is contemplated."} {"id": "PMID:1259186", "title": "Biphasic respiratory depression after fentanyldroperidol or fentanyl alone used to supplement nitrous oxide anesthesia.", "content": "Either fentanyl or Innovar (fentanyl, 0.05 mg/ml, and droperidol 2.5 mg/ml) was administered to supplement nitrous oxide anesthesia for operations on 29 patients. Both fentanyl and Innovar depressed the slope of the rebreathing CO2 response curve during operation to 42 per cent +/- 6 (mean of all intraoperative values, +/- SE) of the awake control value. Following the last injection of drug but with continuation of operation, the slope increased such that it was 77 per cent +/- 8 of control on the patients' arrival in the recovery room. The slope continued to increase to a peak of 103 per cent +/- 9 of control. Soon therafter respiratory depression recurred, as indicated by a decline in the slope to 55 per cent +/- 5 of control, with a subsequent gradual return to 85 per cent +/- 8 of control 230 minutes after the last injection. This biphasic response occurred in 90 per cent (26 of 29) of the patients treated either with fentanyl alone or with Innovar. Full recovery appeared to be more rapid with Innovar than with fentanyl alone. Droperidol did not augment and may have attenuated fentanyl-induced respiratory-depression.", "contents": "Biphasic respiratory depression after fentanyldroperidol or fentanyl alone used to supplement nitrous oxide anesthesia. Either fentanyl or Innovar (fentanyl, 0.05 mg/ml, and droperidol 2.5 mg/ml) was administered to supplement nitrous oxide anesthesia for operations on 29 patients. Both fentanyl and Innovar depressed the slope of the rebreathing CO2 response curve during operation to 42 per cent +/- 6 (mean of all intraoperative values, +/- SE) of the awake control value. Following the last injection of drug but with continuation of operation, the slope increased such that it was 77 per cent +/- 8 of control on the patients' arrival in the recovery room. The slope continued to increase to a peak of 103 per cent +/- 9 of control. Soon therafter respiratory depression recurred, as indicated by a decline in the slope to 55 per cent +/- 5 of control, with a subsequent gradual return to 85 per cent +/- 8 of control 230 minutes after the last injection. This biphasic response occurred in 90 per cent (26 of 29) of the patients treated either with fentanyl alone or with Innovar. Full recovery appeared to be more rapid with Innovar than with fentanyl alone. Droperidol did not augment and may have attenuated fentanyl-induced respiratory-depression."} {"id": "PMID:1259187", "title": "Early and late relative potencies of pancuronium and d-tubocurarine in man.", "content": "In ten patients anesthetized with halothane and nitrous oxide, d-tubocurarine or pancuronium was infused continuously for 80 minutes to produce a constant 90 per cent depression of twitch tension. For the first 30-minutes period, 8.2 +/- 0.32 and 1.09 +/- 0.06 (mean +/- SE) mg/m2 of d-tubocurarine or pancuronium, respectively, were required, and for the last 30-minutes period (50 to 80 minutes of infusion) 2.1 +/- 10.10 and 0.41 +/- 0.02 mg/m2 were required, giving potency ratios of 8.2/1.1, i.e., 7.4, and 2.1/0.41, i.e., 5.1. The difference in potency ratios in the first and last 30-minutes periods implies that potency values determined by single-injection techniques inadequately describe the relative requirements for sustained paralysis. The mean ratios between that amount of relaxant representing tissue uptake and that amount representing metabolism and renal excretion during the first 30 minutes were 3.06 +/- 0.28 for d-tubocurarine and 1.63 +/- 0.19 for pancuronium. The significantly higher ratio for d-tubocurarine implies that its tissue uptake relative to metabolism and renal excretion is greater than that for pancuronium. The higher ratio for d-tubocurarine may be partly explained by its greater binding to plasma and tissue proteins.", "contents": "Early and late relative potencies of pancuronium and d-tubocurarine in man. In ten patients anesthetized with halothane and nitrous oxide, d-tubocurarine or pancuronium was infused continuously for 80 minutes to produce a constant 90 per cent depression of twitch tension. For the first 30-minutes period, 8.2 +/- 0.32 and 1.09 +/- 0.06 (mean +/- SE) mg/m2 of d-tubocurarine or pancuronium, respectively, were required, and for the last 30-minutes period (50 to 80 minutes of infusion) 2.1 +/- 10.10 and 0.41 +/- 0.02 mg/m2 were required, giving potency ratios of 8.2/1.1, i.e., 7.4, and 2.1/0.41, i.e., 5.1. The difference in potency ratios in the first and last 30-minutes periods implies that potency values determined by single-injection techniques inadequately describe the relative requirements for sustained paralysis. The mean ratios between that amount of relaxant representing tissue uptake and that amount representing metabolism and renal excretion during the first 30 minutes were 3.06 +/- 0.28 for d-tubocurarine and 1.63 +/- 0.19 for pancuronium. The significantly higher ratio for d-tubocurarine implies that its tissue uptake relative to metabolism and renal excretion is greater than that for pancuronium. The higher ratio for d-tubocurarine may be partly explained by its greater binding to plasma and tissue proteins."} {"id": "PMID:1259188", "title": "Bulk oxygen and nitrous oxide delivery systems: design and dangers.", "content": "A survey of hospitals with anesthesia residency training programs was undertaken to determine the frequency and types of complications encountered with the use of bulk supplies of oxygen and nitrous oxide. Of the responding hospitals, 98 per cent dispense oxygen from a central source and 80 per cent dispense nitrous oxide from a central source. Nearly a third of the hospitals responding reported the occurrence of serious or potentially serious accidents related to their bulk gas delivery systems. In three instances accidents resulted in patient deaths. More than half of the reported incidents were decreases in oxygen pipeline pressure, often resulting in insufficient delivery of oxygen for clinical use. Most complications related to pipeline accidents could have been prevented by observance of National Fire Protection Association regulations. Anesthesiologists should be familiar with these regulations and should understand the designs of gas delivery systems in their institutions.", "contents": "Bulk oxygen and nitrous oxide delivery systems: design and dangers. A survey of hospitals with anesthesia residency training programs was undertaken to determine the frequency and types of complications encountered with the use of bulk supplies of oxygen and nitrous oxide. Of the responding hospitals, 98 per cent dispense oxygen from a central source and 80 per cent dispense nitrous oxide from a central source. Nearly a third of the hospitals responding reported the occurrence of serious or potentially serious accidents related to their bulk gas delivery systems. In three instances accidents resulted in patient deaths. More than half of the reported incidents were decreases in oxygen pipeline pressure, often resulting in insufficient delivery of oxygen for clinical use. Most complications related to pipeline accidents could have been prevented by observance of National Fire Protection Association regulations. Anesthesiologists should be familiar with these regulations and should understand the designs of gas delivery systems in their institutions."} {"id": "PMID:1259189", "title": "Lidocaine and increased respiratory resistance produced by ultrasonic aerosols.", "content": "Respiratory resistance significantly increased from 5.0 to 8.0 cm H2O/1/sec in anesthetized patients who were given ultrasonically nebulized water for 20 minutes via an endotracheal tube. Intravenous administration of lidocaine failed to reverse the provoked increase in resistance. In another group, respiratory resistance significantly increased from 5.8 to 7.5 cm H2O/1/sec in response to nebulized water despite prior and con-current intravenous administration of lidocaine. In a third group, initial respiratory resistance was 5.6 cm H2O/1/sec and did not increase during a 20-minute challenge with intratracheally administrered ultrasonically nebulized 2 per cent lidocaine. In a final group, resistance was increased from 5.0 to 6.9 cm H2O/1/sec with nebulized water. When challenge was continued with nebulized 2 per cent lidocaine, resistance remained elevated for about 10-12 minutes. It then decreased and returned to its initial control value at about 17 minutes, despite continuing lidocaine aerosol administration. Lidocaine, when administered intratracheally as an aerosol, both prevented and reversed provoked increases in respiratory resistance. Intravenously administered lidocaine was ineffective. Intratracheal administration of ultrasonically nebulized lidocaine might be another useful technique for management of bronchoconstriction in anesthetized patients.", "contents": "Lidocaine and increased respiratory resistance produced by ultrasonic aerosols. Respiratory resistance significantly increased from 5.0 to 8.0 cm H2O/1/sec in anesthetized patients who were given ultrasonically nebulized water for 20 minutes via an endotracheal tube. Intravenous administration of lidocaine failed to reverse the provoked increase in resistance. In another group, respiratory resistance significantly increased from 5.8 to 7.5 cm H2O/1/sec in response to nebulized water despite prior and con-current intravenous administration of lidocaine. In a third group, initial respiratory resistance was 5.6 cm H2O/1/sec and did not increase during a 20-minute challenge with intratracheally administrered ultrasonically nebulized 2 per cent lidocaine. In a final group, resistance was increased from 5.0 to 6.9 cm H2O/1/sec with nebulized water. When challenge was continued with nebulized 2 per cent lidocaine, resistance remained elevated for about 10-12 minutes. It then decreased and returned to its initial control value at about 17 minutes, despite continuing lidocaine aerosol administration. Lidocaine, when administered intratracheally as an aerosol, both prevented and reversed provoked increases in respiratory resistance. Intravenously administered lidocaine was ineffective. Intratracheal administration of ultrasonically nebulized lidocaine might be another useful technique for management of bronchoconstriction in anesthetized patients."} {"id": "PMID:1259190", "title": "Ethanol and contraction of venous smooth muscle.", "content": "Low concentrations of ethanol (17 mM) inhibited development of spontaneous mechanical activity (vasomotion) in isolated rat portal veins. Low concentrations of ethanol potentiated, however, contractions induced by epinephrine, but not those induced by angiotensin or potassium. Higher concentrations of ethanol, such as those associated with surgical anesthesia (100-170 mM), resulted in almost complete suppression of spontaneous contratile responses. These higher concentrations of ethanol: a) attenuate contractions induced by epinephrine, angiotensin, and potassium (K+); b) cause noncompetitive displacement of the dose-response curves of these vasoactive compounds; c) attenuate calcium (Ca++)-induced contractions of K+-depolarized portal veins; d) relax drug-induced, as well as Ca++-induced, contractions of portal veins. The profound depressant actions of ethanol are not mimicked by alpha-adrenergic, histaminergic, cholinergic, or serotonergic blocking drugs, nor are they attributable to actions on beta-adrenergic receptors. The direct vasodepressant actions of ethanol on isolated venous smooth muscle may play a significant role in alcohol-induced peripheral vasodiatation seen in man and animals.", "contents": "Ethanol and contraction of venous smooth muscle. Low concentrations of ethanol (17 mM) inhibited development of spontaneous mechanical activity (vasomotion) in isolated rat portal veins. Low concentrations of ethanol potentiated, however, contractions induced by epinephrine, but not those induced by angiotensin or potassium. Higher concentrations of ethanol, such as those associated with surgical anesthesia (100-170 mM), resulted in almost complete suppression of spontaneous contratile responses. These higher concentrations of ethanol: a) attenuate contractions induced by epinephrine, angiotensin, and potassium (K+); b) cause noncompetitive displacement of the dose-response curves of these vasoactive compounds; c) attenuate calcium (Ca++)-induced contractions of K+-depolarized portal veins; d) relax drug-induced, as well as Ca++-induced, contractions of portal veins. The profound depressant actions of ethanol are not mimicked by alpha-adrenergic, histaminergic, cholinergic, or serotonergic blocking drugs, nor are they attributable to actions on beta-adrenergic receptors. The direct vasodepressant actions of ethanol on isolated venous smooth muscle may play a significant role in alcohol-induced peripheral vasodiatation seen in man and animals."} {"id": "PMID:1259191", "title": "Nitroprusside-induced cyanide poisoning: antidotal effect of hydroxocobalamin.", "content": "Sodium nitroprusside was investigated as a potential source of cyanide poisoning, Whole-blood cyanide determinations were performed on arterial samples from baboons receiving nitroprusside while anesthetized. There was a statistically significant increase in cyanide levels, as well as development of tachyphylaxis and severe metabolic acidosis. Hydroxocobalamin (vitamin B12a) infused simultaneously with nitroprusside significantly lessened the increase in cyanide levels and eliminated the development of metabolic acidosis. Nitroprusside can cause cyanide intoxication in the baboon, and hydroxocobalamin appears to be an effective antidote.", "contents": "Nitroprusside-induced cyanide poisoning: antidotal effect of hydroxocobalamin. Sodium nitroprusside was investigated as a potential source of cyanide poisoning, Whole-blood cyanide determinations were performed on arterial samples from baboons receiving nitroprusside while anesthetized. There was a statistically significant increase in cyanide levels, as well as development of tachyphylaxis and severe metabolic acidosis. Hydroxocobalamin (vitamin B12a) infused simultaneously with nitroprusside significantly lessened the increase in cyanide levels and eliminated the development of metabolic acidosis. Nitroprusside can cause cyanide intoxication in the baboon, and hydroxocobalamin appears to be an effective antidote."} {"id": "PMID:1259200", "title": "A systematic approach to the evaluation of immunological disease patterns.", "content": "An approach to the detection and investigation of immunological disease patterns is presented in the form of a relationship of etiology to disease and the major diagnostic procedures available to evaluate the etiological agents. The presentation is made in the form of a preamble which outlines the mechanisms of each class of dysfunction. Four tables are included which serve to amplify and detail the format of approach and the immune mechanisms.", "contents": "A systematic approach to the evaluation of immunological disease patterns. An approach to the detection and investigation of immunological disease patterns is presented in the form of a relationship of etiology to disease and the major diagnostic procedures available to evaluate the etiological agents. The presentation is made in the form of a preamble which outlines the mechanisms of each class of dysfunction. Four tables are included which serve to amplify and detail the format of approach and the immune mechanisms."} {"id": "PMID:1259201", "title": "Allergy and learning disabilities in children.", "content": "Allergic children suffering from learning disabilities, hyperactivity, fatigue, incoordination and irritability who were treated by conventional allergic methods showed a marked improvement in ability to learn, reduction of hyperactivity and incoordination, and ability to perform intelligence tests. The objective neurological studies showed no consistent changes as a result of one year of allergy therapy.", "contents": "Allergy and learning disabilities in children. Allergic children suffering from learning disabilities, hyperactivity, fatigue, incoordination and irritability who were treated by conventional allergic methods showed a marked improvement in ability to learn, reduction of hyperactivity and incoordination, and ability to perform intelligence tests. The objective neurological studies showed no consistent changes as a result of one year of allergy therapy."} {"id": "PMID:1259202", "title": "Comparison of skin tests and RAST in the diagnosis of atopic hypersensitivity.", "content": "Prick, intracutaneous tests and the radioallergosorbent test (RAST) were performed with 12 common allergens in 50 consecutive patients who required skin testing during an allergy investigation. Results of prick test and RAST showed agreement in 82.7% of tests but positive prick tests were much commoner than positive RAST tests. When intracutaneous tests were required to obtain a positive skin test, agreement between skin test and RAST fell to 66.5%.", "contents": "Comparison of skin tests and RAST in the diagnosis of atopic hypersensitivity. Prick, intracutaneous tests and the radioallergosorbent test (RAST) were performed with 12 common allergens in 50 consecutive patients who required skin testing during an allergy investigation. Results of prick test and RAST showed agreement in 82.7% of tests but positive prick tests were much commoner than positive RAST tests. When intracutaneous tests were required to obtain a positive skin test, agreement between skin test and RAST fell to 66.5%."} {"id": "PMID:1259203", "title": "Allergy and recurrent urinary tract infections in childhood. II.", "content": "Fifty selected patients with recurrent urinary tract infections and allergy problems were treated with a comprehensive allergy regime. The results demonstrated that the recurring urinary tract infections ceased or were distinctly alleviated by treatment of the presenting allergic condition. Of the 50 patients 42 were definitely benefited.", "contents": "Allergy and recurrent urinary tract infections in childhood. II. Fifty selected patients with recurrent urinary tract infections and allergy problems were treated with a comprehensive allergy regime. The results demonstrated that the recurring urinary tract infections ceased or were distinctly alleviated by treatment of the presenting allergic condition. Of the 50 patients 42 were definitely benefited."} {"id": "PMID:1259204", "title": "Diabetes mellitus and insulin in an aspirin sensitive asthmatic.", "content": "The infrequency of diabetes mellitus and asthma in the same individual is re-examined. The antagonism between epinephrine and insulin, as suggested by Konig in 1935, is indeed accurate. The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells. It is felt that this effect is probably an in vivo effect produced via the vagus nerve and alpha-adrenergic receptor system stimulation. This would explain the mechanism of aggravation of asthma by excess insulin. Dr. Petersen's studies, the negative intradermal skin tests to insulin and the absence of change on either beef or pork insulin usage by our patient all point to a nonatopic factor in the aggravation of the asthma of this patient. In the uncommon occurrence of asthma and diabetes in the same patient, insulin dosage should be considered as a factor in all such asthmatics who do not respond well to conventional therapy. Two additional asthmatics who also have diabetes did improve with cessation of nocturnal asthma by a reduction of their evening dose of insulin. A high fat, low carbohydrate diet, as suggested by Abrahamson to avoid dietary hyperinsulinism, is certainly worth considering in patients with nocturnal asthma. If patients cannot be made to follow a diet requiring frequent feedings high in protein and fats and low in carbohydrates, another approach suggests itself. Abrahamson was able to relieve the patients who developed nocturnal asthma with hypoglycemia by having them drink a glass of milk. Assuming other causes have been eliminated and a patient awakens each day at 3:00 a.m., an alarm clock could be set at 2:00 a.m. Milk or a milk substitute in milk sensitive patients could be taken at 2:00 a.m. to raise the blood sugar and hopefully prevent the asthma associated with hypoglycemia. Also to be noted is the ubiquitous use of tartrazine in so many drugs, including those used to relieve asthmatic symptoms. Inasmuch as tartrazine so frequently aggravates the aspirin sensitive asthmatic, it would be wise for pharmaceutical companies to become cognizant of this fact and delete tartrazine from their antiasthmatic preparations.", "contents": "Diabetes mellitus and insulin in an aspirin sensitive asthmatic. The infrequency of diabetes mellitus and asthma in the same individual is re-examined. The antagonism between epinephrine and insulin, as suggested by Konig in 1935, is indeed accurate. The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells. It is felt that this effect is probably an in vivo effect produced via the vagus nerve and alpha-adrenergic receptor system stimulation. This would explain the mechanism of aggravation of asthma by excess insulin. Dr. Petersen's studies, the negative intradermal skin tests to insulin and the absence of change on either beef or pork insulin usage by our patient all point to a nonatopic factor in the aggravation of the asthma of this patient. In the uncommon occurrence of asthma and diabetes in the same patient, insulin dosage should be considered as a factor in all such asthmatics who do not respond well to conventional therapy. Two additional asthmatics who also have diabetes did improve with cessation of nocturnal asthma by a reduction of their evening dose of insulin. A high fat, low carbohydrate diet, as suggested by Abrahamson to avoid dietary hyperinsulinism, is certainly worth considering in patients with nocturnal asthma. If patients cannot be made to follow a diet requiring frequent feedings high in protein and fats and low in carbohydrates, another approach suggests itself. Abrahamson was able to relieve the patients who developed nocturnal asthma with hypoglycemia by having them drink a glass of milk. Assuming other causes have been eliminated and a patient awakens each day at 3:00 a.m., an alarm clock could be set at 2:00 a.m. Milk or a milk substitute in milk sensitive patients could be taken at 2:00 a.m. to raise the blood sugar and hopefully prevent the asthma associated with hypoglycemia. Also to be noted is the ubiquitous use of tartrazine in so many drugs, including those used to relieve asthmatic symptoms. Inasmuch as tartrazine so frequently aggravates the aspirin sensitive asthmatic, it would be wise for pharmaceutical companies to become cognizant of this fact and delete tartrazine from their antiasthmatic preparations."} {"id": "PMID:1259210", "title": "Cardiopulmonary effects of enflurane and isoflurane in the dog.", "content": "The cardiopulmonary effects of 2 new inhalant anesthetics, enflurane and isoflurane, were studied in nonsedated, previously instrumented, awake dogs. Base line values were determined, and anesthesia was induced and maintained with the drug being studied. Enflurane depressed cardiopulmonary function to a greater extent than isoflurane. The depression of cardiopulmonary function from both agents increased with increasing depth of anesthesia. Enflurance produced muslce twitching, but isoflurane did not.", "contents": "Cardiopulmonary effects of enflurane and isoflurane in the dog. The cardiopulmonary effects of 2 new inhalant anesthetics, enflurane and isoflurane, were studied in nonsedated, previously instrumented, awake dogs. Base line values were determined, and anesthesia was induced and maintained with the drug being studied. Enflurane depressed cardiopulmonary function to a greater extent than isoflurane. The depression of cardiopulmonary function from both agents increased with increasing depth of anesthesia. Enflurance produced muslce twitching, but isoflurane did not."} {"id": "PMID:1259211", "title": "Cell-mediated immunity and age at vaccination associated with measles inoculation and protection of dogs against canine distemper.", "content": "The antibody-mediated immune response (AMIR) of dogs to measles and canine distemper viruses has been described. However, there is little information on the cell-mediated immune response (CMIR). The AMIR and the CMIR of dogs to canine distemper and to measles were examined. The CMIR was determined for 6 weeks by measuring the 3H-thymidine uptake by immune lymphocytes in the lymphocyte transformation test. Concurrently, canine distemper and measles virus serum-neutralization antibodies were measured by a microtitration serum-neutralization test. Dogs vaccinated with canine distemper virus had a CMIR and an AMIR to canine distemper. However, measles virus-vaccinated dogs had only a CMIR to canine distemper. A CMIR in the absence of an AMIR indicates that cell-mediated immunity is the most important immune mechanism in protecting measles virus-vaccinated dogs against canine distemper. Development of CMIR and AMIR to canine distemper and measles antigens depended on the age of the dog at the time of vaccination. Adult and juvenile dogs had immune responses to both canine distemper and measles. Neither virus, however, elicited an immune response in neonates.", "contents": "Cell-mediated immunity and age at vaccination associated with measles inoculation and protection of dogs against canine distemper. The antibody-mediated immune response (AMIR) of dogs to measles and canine distemper viruses has been described. However, there is little information on the cell-mediated immune response (CMIR). The AMIR and the CMIR of dogs to canine distemper and to measles were examined. The CMIR was determined for 6 weeks by measuring the 3H-thymidine uptake by immune lymphocytes in the lymphocyte transformation test. Concurrently, canine distemper and measles virus serum-neutralization antibodies were measured by a microtitration serum-neutralization test. Dogs vaccinated with canine distemper virus had a CMIR and an AMIR to canine distemper. However, measles virus-vaccinated dogs had only a CMIR to canine distemper. A CMIR in the absence of an AMIR indicates that cell-mediated immunity is the most important immune mechanism in protecting measles virus-vaccinated dogs against canine distemper. Development of CMIR and AMIR to canine distemper and measles antigens depended on the age of the dog at the time of vaccination. Adult and juvenile dogs had immune responses to both canine distemper and measles. Neither virus, however, elicited an immune response in neonates."} {"id": "PMID:1259212", "title": "Critical tests and safety studies on trichlorfon as an antiparasitic agent in the horse.", "content": "Three series of critical tests were completed on a combined total of 46 horses to determine the efficacy of single doses of trichlorfon against bots, ascarids, pinworms, and large strongyles. Different formulations of trichlorfon were administered by tubing intragastrically, mixing with the daily grain ration, injecting intramuscularly, or pouring on the back at dose rates between 20 and 100 mg/kg. Administration by feeding tended to be more efficacious for removal of bots and less toxic to the horese than administration by stomach tube. In many of the tests, trichlorfon was given in the grain ration at the dose rate of 40 mg/kg of body weight, and the aggregate average removals of 2nd and 3rd instars of Gastrophilus intestinalis and Gasterophilus nasalis in the 3 series of tests were between 97 and 100%. Removal of Parascaris equorum was equally efficacious with both the intubation and the grain feeding methods of dosing, and at the dose rate of 40 mg/kg, the aggregate averages were 99 and 100% in the 3 series. Removal of Oxyuris equi was variable--aggregate averages were between 11 (1 infected horse in the initial series) and 96 (5 infected horses in the 3rd series) to 100% (7 infected horses in the 2nd series). Large strongyles, Strongylus vulgaris and Strongylus edentatus were almost completely refractory to the 40-mg/kg dose rate of trichlorfon. Dose rates of 40 mg/kg and less were generally well tolerated by the critical test horses. Higher dose rates (60 and 80 mg/kg) administered by stomach tube induced moderately severe to severe colic and diarrhea, whereas a dose of 80 mg/kg given in the feed resulted in only a transient softening of the feces. Likewise, 5 consecutive doses, 1 week between doses, of a bolus formulation given at the rate of 80 mg/kg to 4 horses were well tolerated. Clinical trials involving a total of 2,294 treatments of trichlorfon at dose rate of 35 to 40 mg/kg in pregnant and nonpregnant mares, stallions, suckling and weanling foals, yearlings, and horses in training on 38 farms in central Kentucky did not cause notable adverse clinical effects.", "contents": "Critical tests and safety studies on trichlorfon as an antiparasitic agent in the horse. Three series of critical tests were completed on a combined total of 46 horses to determine the efficacy of single doses of trichlorfon against bots, ascarids, pinworms, and large strongyles. Different formulations of trichlorfon were administered by tubing intragastrically, mixing with the daily grain ration, injecting intramuscularly, or pouring on the back at dose rates between 20 and 100 mg/kg. Administration by feeding tended to be more efficacious for removal of bots and less toxic to the horese than administration by stomach tube. In many of the tests, trichlorfon was given in the grain ration at the dose rate of 40 mg/kg of body weight, and the aggregate average removals of 2nd and 3rd instars of Gastrophilus intestinalis and Gasterophilus nasalis in the 3 series of tests were between 97 and 100%. Removal of Parascaris equorum was equally efficacious with both the intubation and the grain feeding methods of dosing, and at the dose rate of 40 mg/kg, the aggregate averages were 99 and 100% in the 3 series. Removal of Oxyuris equi was variable--aggregate averages were between 11 (1 infected horse in the initial series) and 96 (5 infected horses in the 3rd series) to 100% (7 infected horses in the 2nd series). Large strongyles, Strongylus vulgaris and Strongylus edentatus were almost completely refractory to the 40-mg/kg dose rate of trichlorfon. Dose rates of 40 mg/kg and less were generally well tolerated by the critical test horses. Higher dose rates (60 and 80 mg/kg) administered by stomach tube induced moderately severe to severe colic and diarrhea, whereas a dose of 80 mg/kg given in the feed resulted in only a transient softening of the feces. Likewise, 5 consecutive doses, 1 week between doses, of a bolus formulation given at the rate of 80 mg/kg to 4 horses were well tolerated. Clinical trials involving a total of 2,294 treatments of trichlorfon at dose rate of 35 to 40 mg/kg in pregnant and nonpregnant mares, stallions, suckling and weanling foals, yearlings, and horses in training on 38 farms in central Kentucky did not cause notable adverse clinical effects."} {"id": "PMID:1259213", "title": "Influence of prednisolone on intravascular granulocyte kinetics of calves under nonsteady state conditions.", "content": "The influence of prednisolone on granulocyte kinetics in calves was evaluated under nonsteady state conditions, using chromium-51 as a cell label. The kinetic pattern observed was similar to that described for persons. Interpretation of results indicated that alteration from steady state to granulocytosis was the result of an increase in input from the storage pool and that shifts occurred in the distribution of cells between the marginating and circulating pools during the period of rapidly changing kinetic patterns. Granulocyte kinetic variables of a calf under induced physiologic stress demonstrated a kinetic pattern similar to that of the calves given prednisolone. There was a rapid enlargement of the total granulocyte pool size and a greater than twofold increase in clearance halftime compared with those in calves of a similar age group.", "contents": "Influence of prednisolone on intravascular granulocyte kinetics of calves under nonsteady state conditions. The influence of prednisolone on granulocyte kinetics in calves was evaluated under nonsteady state conditions, using chromium-51 as a cell label. The kinetic pattern observed was similar to that described for persons. Interpretation of results indicated that alteration from steady state to granulocytosis was the result of an increase in input from the storage pool and that shifts occurred in the distribution of cells between the marginating and circulating pools during the period of rapidly changing kinetic patterns. Granulocyte kinetic variables of a calf under induced physiologic stress demonstrated a kinetic pattern similar to that of the calves given prednisolone. There was a rapid enlargement of the total granulocyte pool size and a greater than twofold increase in clearance halftime compared with those in calves of a similar age group."} {"id": "PMID:1259214", "title": "Experimentally induced Mycobacterium avium serotype 8 infection in swine.", "content": "Five of 6 swine experimentally inoculated with Mycobacterium avium serotype 8 had microgranulomas in the cervical or mesenteric lymph nodes at necropsy 92 days later. In vivo tuberculin skin reactivity and in vitro lymphocyte immunostimulation responses were evaluated at 10 and 12 weeks after the pigs were inoculated. Positive responses were obtained on both tests in inoculated pigs, whereas test results in noninoculated pigs and pigs given killed bacterial cells were negative. Mycobacterium avium serotype 8 was isolated at necropsy from the cervical or mesenteric lymph nodes of each of the pigs inoculated with viable microorganisms and from the 2 pigs kept in the pen with inoculated swine. Mycobacteria were not isolated from tissues of the noninoculated swine or those given killed cells.", "contents": "Experimentally induced Mycobacterium avium serotype 8 infection in swine. Five of 6 swine experimentally inoculated with Mycobacterium avium serotype 8 had microgranulomas in the cervical or mesenteric lymph nodes at necropsy 92 days later. In vivo tuberculin skin reactivity and in vitro lymphocyte immunostimulation responses were evaluated at 10 and 12 weeks after the pigs were inoculated. Positive responses were obtained on both tests in inoculated pigs, whereas test results in noninoculated pigs and pigs given killed bacterial cells were negative. Mycobacterium avium serotype 8 was isolated at necropsy from the cervical or mesenteric lymph nodes of each of the pigs inoculated with viable microorganisms and from the 2 pigs kept in the pen with inoculated swine. Mycobacteria were not isolated from tissues of the noninoculated swine or those given killed cells."} {"id": "PMID:1259215", "title": "Electron microscopic studies of estrogen-induced ciliogenesis and secretion in uterine tube of the gilt.", "content": "The time required for occurrence of estrogen-induced uterine tubal (oviductal) ciliogenesis and for differentiation of secretory cells was studied, utilizing electron microscopy procedures. Sixteen cycling gilts were ovariectomized; 3 to 4 months later, 12 principal gilts were each given subcutaneous injections of 17 beta-estradiol in 0.5 ml of corn oil at the rate of 200 mug/day, and 4 control gilts were given injections of corn oil only at the rate of 0.5 ml/day. Two principals each were killed on days 1, 2, 3, 4, 5, and 7 after start of treatment. The epithelial heights were low and completely atrophied 3 to 4 months after ovariectomy. Uterine tubal cilia were absent in all the control gilts. Cytologic changes were not seen in the atrophied epithelium of ovariectomized gilts 1 day after estradiol treatment, but definite proliferative elements consisting of an extensive fibrillar meshwork encrusted with granules (60 to 80 nm) were observed in close association with the nuclear envelope and in the apical cytoplasm after 2 days of estradiol treatment. By day 3, enlarged electron-opaque granules referred to as condensation forms, undergoing various stages of depletion, were closely associated with radially arranged procentrioles. These associations have been referred to as generative complexes. The presence of many generative complexes indicates that maximal production of basal bodies can be expected after 3 days of treatment with estradiol. The depletion of the condensation forms produced hollow spheres with thin walls as the procentrioles grew in length and assembled their microtubules. Enlarged mature-appearing basal bodies were abundant in the cytoplasm after 3 days of estradiol treatment. These bodies aligned themselves linearly along the luminal surface of the cell. Small ciliary buds were then formed above the cell surface, and ciliary filamentogenesis occurred in the bud. Motile cilia were observed on day 3, but cilia numbers increased markedly between day 4 and days 5 and 7. Procentrioles were generated from the diplosomal centriole after 2 days of estradiol treatment. These observations have provided evidence for both ancentriolar and centriolar basal body replication in the ciliated cells of uterine tube of the gilt. Maximal secretory cell differentiation occurred after 3 days of estradiol treatment. Hypertrophy of cytoplasmic organelles was evident on day 3, but the number of secretory granules and amount of rough endoplasmic reticulum increased markedly on days 5 and 7. Close association of secretory granules, Golgi apparatus, and endoplasmic reticulum was evident after estadiol treatment. These data indicate that both ciliated and secretory cells are sensitive to estrogen.", "contents": "Electron microscopic studies of estrogen-induced ciliogenesis and secretion in uterine tube of the gilt. The time required for occurrence of estrogen-induced uterine tubal (oviductal) ciliogenesis and for differentiation of secretory cells was studied, utilizing electron microscopy procedures. Sixteen cycling gilts were ovariectomized; 3 to 4 months later, 12 principal gilts were each given subcutaneous injections of 17 beta-estradiol in 0.5 ml of corn oil at the rate of 200 mug/day, and 4 control gilts were given injections of corn oil only at the rate of 0.5 ml/day. Two principals each were killed on days 1, 2, 3, 4, 5, and 7 after start of treatment. The epithelial heights were low and completely atrophied 3 to 4 months after ovariectomy. Uterine tubal cilia were absent in all the control gilts. Cytologic changes were not seen in the atrophied epithelium of ovariectomized gilts 1 day after estradiol treatment, but definite proliferative elements consisting of an extensive fibrillar meshwork encrusted with granules (60 to 80 nm) were observed in close association with the nuclear envelope and in the apical cytoplasm after 2 days of estradiol treatment. By day 3, enlarged electron-opaque granules referred to as condensation forms, undergoing various stages of depletion, were closely associated with radially arranged procentrioles. These associations have been referred to as generative complexes. The presence of many generative complexes indicates that maximal production of basal bodies can be expected after 3 days of treatment with estradiol. The depletion of the condensation forms produced hollow spheres with thin walls as the procentrioles grew in length and assembled their microtubules. Enlarged mature-appearing basal bodies were abundant in the cytoplasm after 3 days of estradiol treatment. These bodies aligned themselves linearly along the luminal surface of the cell. Small ciliary buds were then formed above the cell surface, and ciliary filamentogenesis occurred in the bud. Motile cilia were observed on day 3, but cilia numbers increased markedly between day 4 and days 5 and 7. Procentrioles were generated from the diplosomal centriole after 2 days of estradiol treatment. These observations have provided evidence for both ancentriolar and centriolar basal body replication in the ciliated cells of uterine tube of the gilt. Maximal secretory cell differentiation occurred after 3 days of estradiol treatment. Hypertrophy of cytoplasmic organelles was evident on day 3, but the number of secretory granules and amount of rough endoplasmic reticulum increased markedly on days 5 and 7. Close association of secretory granules, Golgi apparatus, and endoplasmic reticulum was evident after estadiol treatment. These data indicate that both ciliated and secretory cells are sensitive to estrogen."} {"id": "PMID:1259216", "title": "Efficacy studies on Haemophilus gallinarum bacterin preparations.", "content": "Broth cultures inactivated and potentiated by selected methods were tested in chickens for efficacy against homologous and heterologous challenge inoculation, using 2 serotype A strains of Haemophilus gallinarum. Although the 2 strains were within the same serotype, they failed to cross protect. One dose of thimerosal-inactivated bacterin was protective against homologous challenge, but 2 doses of formalin-inactivated bacterin were required. A bivalent bacterin protected chickens well against 1 strain, but not the other, at the 1-dose level.", "contents": "Efficacy studies on Haemophilus gallinarum bacterin preparations. Broth cultures inactivated and potentiated by selected methods were tested in chickens for efficacy against homologous and heterologous challenge inoculation, using 2 serotype A strains of Haemophilus gallinarum. Although the 2 strains were within the same serotype, they failed to cross protect. One dose of thimerosal-inactivated bacterin was protective against homologous challenge, but 2 doses of formalin-inactivated bacterin were required. A bivalent bacterin protected chickens well against 1 strain, but not the other, at the 1-dose level."} {"id": "PMID:1259217", "title": "Evaluation of radioiodinated human serum albumin in the dog for assessment of hemodynamic function.", "content": "Radioiodinated human and dog serum albumins, each labeled with a different radioisotope of iodine (125I and 131I, respectively), were injected intravenously into dogs. Plasma volumes and plasma clearance half times were used for the comparative evaluation of the 2 radiopharmaceuticals. After repeated injections in a 6-week period, differences in these values could not be demonstrated. Plasma volumes obtained with both radioiodinated serum albumins compared favourably with the previously reported values in dogs.", "contents": "Evaluation of radioiodinated human serum albumin in the dog for assessment of hemodynamic function. Radioiodinated human and dog serum albumins, each labeled with a different radioisotope of iodine (125I and 131I, respectively), were injected intravenously into dogs. Plasma volumes and plasma clearance half times were used for the comparative evaluation of the 2 radiopharmaceuticals. After repeated injections in a 6-week period, differences in these values could not be demonstrated. Plasma volumes obtained with both radioiodinated serum albumins compared favourably with the previously reported values in dogs."} {"id": "PMID:1259218", "title": "A procedure for pulmonary lavage in mice.", "content": "A method for the pulmonary lavage of mice is described. The procedure includes exsanguination of anesthetized mice by severting the renal artery, inserting a tracheal catheter in situ, and repeatedly injecting and aspirating 0.9% sodium chloride solution. Protein was recovered from the cell-free lavage fluid even after a given mouse was lavaged several times. The major part of the protein, however, was obtained with 1-ml washes repeated 3 times. Approximately 0.563 mg of protein was recovered by the procedure from a 29-g mouse. Four lavages per mouse yielded approximately 2.9 x 106 free cells.", "contents": "A procedure for pulmonary lavage in mice. A method for the pulmonary lavage of mice is described. The procedure includes exsanguination of anesthetized mice by severting the renal artery, inserting a tracheal catheter in situ, and repeatedly injecting and aspirating 0.9% sodium chloride solution. Protein was recovered from the cell-free lavage fluid even after a given mouse was lavaged several times. The major part of the protein, however, was obtained with 1-ml washes repeated 3 times. Approximately 0.563 mg of protein was recovered by the procedure from a 29-g mouse. Four lavages per mouse yielded approximately 2.9 x 106 free cells."} {"id": "PMID:1259219", "title": "Intestinal infection of neonatal dogs with canine coronavirus 1-71: studies by virologic, histologic, histochemical, and immunofluorescent techniques.", "content": "Enteritis induced in neonatal dogs by oral inoculation of coronavirus 1-71 was studied by virologic, histologic, histochemical, and immunofluorescent antibody methods. The enteritis, accompanied by diarrhea, developed in 4 to 7 days and was characterized by atrophy and fusion of intestinal villi and deepening of crypts, increase in cellularity of the lamina propria, flattening of epithelial cells, and discharge of goblet cells. Intra-epithelial enzyme activities generally were depressed. Specific immunofluorescent antibody reactions were present in villous epithelium of the duodenum starting on postinoculation day 2 and of the ileum on day 4. Epiehtlium of the colon showed no reaction. Virus was present in the feces for 6 to 9 days and was recovered from the small and large intestines from day 2 through day 10. The infection was not fatal and was self limiting; the diarrhea stopped between 1 and 2 weeks. The intestinal mucosa also started recovering by the end of week 1, proceeding caudally from the duodenum.", "contents": "Intestinal infection of neonatal dogs with canine coronavirus 1-71: studies by virologic, histologic, histochemical, and immunofluorescent techniques. Enteritis induced in neonatal dogs by oral inoculation of coronavirus 1-71 was studied by virologic, histologic, histochemical, and immunofluorescent antibody methods. The enteritis, accompanied by diarrhea, developed in 4 to 7 days and was characterized by atrophy and fusion of intestinal villi and deepening of crypts, increase in cellularity of the lamina propria, flattening of epithelial cells, and discharge of goblet cells. Intra-epithelial enzyme activities generally were depressed. Specific immunofluorescent antibody reactions were present in villous epithelium of the duodenum starting on postinoculation day 2 and of the ileum on day 4. Epiehtlium of the colon showed no reaction. Virus was present in the feces for 6 to 9 days and was recovered from the small and large intestines from day 2 through day 10. The infection was not fatal and was self limiting; the diarrhea stopped between 1 and 2 weeks. The intestinal mucosa also started recovering by the end of week 1, proceeding caudally from the duodenum."} {"id": "PMID:1259220", "title": "General anesthesia with methoxyflurane given intravenously to the dog.", "content": "Dogs were anesthetized with liquid methoxyflurane administered intravenously by gaseous diffusion through sealed medical grade silicone rubber tubing placed in the femoral vein. A similar catheter placed in the other femoral vein and connected to a pressure transducer measured the increase in intraluminal pressure due to methoxyflurane diffusion into the 2nd catheter from the bloodstream 20 seconds after the catheter was flushed with room air. These pressures were plotted against venous blood methoxyflurane concentration, as determined by gas chromatography, for increasing lengths of anesthetic-administering catheter exposed to the bloodstream.", "contents": "General anesthesia with methoxyflurane given intravenously to the dog. Dogs were anesthetized with liquid methoxyflurane administered intravenously by gaseous diffusion through sealed medical grade silicone rubber tubing placed in the femoral vein. A similar catheter placed in the other femoral vein and connected to a pressure transducer measured the increase in intraluminal pressure due to methoxyflurane diffusion into the 2nd catheter from the bloodstream 20 seconds after the catheter was flushed with room air. These pressures were plotted against venous blood methoxyflurane concentration, as determined by gas chromatography, for increasing lengths of anesthetic-administering catheter exposed to the bloodstream."} {"id": "PMID:1259221", "title": "Pregnancy termination in dogs with novel nonhormonal compounds.", "content": "Resorption of the products of fertilization was induced in bitches given (subcutaneously) single or multiple doses of the nonhormonal compounds L-10492 and L-10503 during the first half of gestation; also resorption or expulsion of the conceptus was induced when these compounds were given during the latter part of pregnancy. The smallest doses were required at a time immediately after implantation of the fertilized ova in the uterus. Effectiveness and appearance of side effects were dose-dependent. These consisted of decreased appetite, loss of body weight, and diarrhea (feces sometimes containing streaks of blood). Bitches which had aborted returned to estrus within normal intervals of time, exhibited normal mating behavior, and were fertile. They had normal deliveries and lactation, and the pups were normal. The mechanism of action does not involve effects on nidation and the compounds were not luteolytic, but probably involved the uteroplacental complex.", "contents": "Pregnancy termination in dogs with novel nonhormonal compounds. Resorption of the products of fertilization was induced in bitches given (subcutaneously) single or multiple doses of the nonhormonal compounds L-10492 and L-10503 during the first half of gestation; also resorption or expulsion of the conceptus was induced when these compounds were given during the latter part of pregnancy. The smallest doses were required at a time immediately after implantation of the fertilized ova in the uterus. Effectiveness and appearance of side effects were dose-dependent. These consisted of decreased appetite, loss of body weight, and diarrhea (feces sometimes containing streaks of blood). Bitches which had aborted returned to estrus within normal intervals of time, exhibited normal mating behavior, and were fertile. They had normal deliveries and lactation, and the pups were normal. The mechanism of action does not involve effects on nidation and the compounds were not luteolytic, but probably involved the uteroplacental complex."} {"id": "PMID:1259222", "title": "Consecutive water provocative tests in normal and glaucomatous Beagles.", "content": "Water provocative tests were evaluated in normal and glaucomatous Beagles. Schiotz tonometry was performed before water was administered (50 ml/kg) by stomach tube and for the next 90 minutes. The mean increase in Schiotz tonometric values in normal dogs ranged from 3.1 to 8.6 mm of Hg and in glaucomatous dogs, 7.3 to 19.9 mm of Hg. Beagles with glaucoma had progressive, gradually increased responses to water provocative tests.", "contents": "Consecutive water provocative tests in normal and glaucomatous Beagles. Water provocative tests were evaluated in normal and glaucomatous Beagles. Schiotz tonometry was performed before water was administered (50 ml/kg) by stomach tube and for the next 90 minutes. The mean increase in Schiotz tonometric values in normal dogs ranged from 3.1 to 8.6 mm of Hg and in glaucomatous dogs, 7.3 to 19.9 mm of Hg. Beagles with glaucoma had progressive, gradually increased responses to water provocative tests."} {"id": "PMID:1259223", "title": "Immunization against feline calicivirus infection.", "content": "Forty-three cats (experiments 1 and 2) were vaccinated (2 doses, 27 and 30 days between doses) with the F-9 strain of feline calicivirus by the intramuscular route. There was no untoward response in any of the cats to the administration of the vaccinal virus nor was there spread of the virus from 20 vaccinated cats to nonvaccinated cats held in contact during the next 6 months (experiment 2). The vaccinated cats developed serum-neutralizing antibodies that were increased further after the 2nd vaccination. The level of serum-neutralizing antibodies was related to the quantity of vaccinal virus administered. Twenty-three cats vaccinated with the F-9 strain were protected to a significant degree when challenge exposed to virulent calicivirus strain FPV-255 (experiment 1).", "contents": "Immunization against feline calicivirus infection. Forty-three cats (experiments 1 and 2) were vaccinated (2 doses, 27 and 30 days between doses) with the F-9 strain of feline calicivirus by the intramuscular route. There was no untoward response in any of the cats to the administration of the vaccinal virus nor was there spread of the virus from 20 vaccinated cats to nonvaccinated cats held in contact during the next 6 months (experiment 2). The vaccinated cats developed serum-neutralizing antibodies that were increased further after the 2nd vaccination. The level of serum-neutralizing antibodies was related to the quantity of vaccinal virus administered. Twenty-three cats vaccinated with the F-9 strain were protected to a significant degree when challenge exposed to virulent calicivirus strain FPV-255 (experiment 1)."} {"id": "PMID:1259224", "title": "Feline caliciviral disease: experimental immunoprophylaxis.", "content": "An attenuated feline calicivirus (FCV) was administered intramuscularly to specific-pathogen-free cats. Vaccination did not cause signs of illness. Oropharyngeal replication of attenuated FCV was not detected, nor was there evidence of virus transmission to contact-control cats. Antiviral neutralizing antibody was present in the serum of all vaccinated cats 7 days after they were given the 2nd intramuscular dose of immunogen. Vaccinated and control cats were challenge exposed to aerosols of a virulent FCV strain. All controls developed severe pneumonia and died within 7 days after this challenge exposure. In the vaccinated cats, signs of illness were absent or minimal; pulmonary lesions were milder and less extensive than those in the control cats. Feline calicivirus was isolated from ocular, nasal, and oropharyngeal swabbings from both control and vaccinated cats after viral challenge. Results indicate protective immunity to FCV disease can be induced by intramuscular administration of an attenuated FCV.", "contents": "Feline caliciviral disease: experimental immunoprophylaxis. An attenuated feline calicivirus (FCV) was administered intramuscularly to specific-pathogen-free cats. Vaccination did not cause signs of illness. Oropharyngeal replication of attenuated FCV was not detected, nor was there evidence of virus transmission to contact-control cats. Antiviral neutralizing antibody was present in the serum of all vaccinated cats 7 days after they were given the 2nd intramuscular dose of immunogen. Vaccinated and control cats were challenge exposed to aerosols of a virulent FCV strain. All controls developed severe pneumonia and died within 7 days after this challenge exposure. In the vaccinated cats, signs of illness were absent or minimal; pulmonary lesions were milder and less extensive than those in the control cats. Feline calicivirus was isolated from ocular, nasal, and oropharyngeal swabbings from both control and vaccinated cats after viral challenge. Results indicate protective immunity to FCV disease can be induced by intramuscular administration of an attenuated FCV."} {"id": "PMID:1259225", "title": "Large monocytoid cell in mononuclear cell fraction of bovine blood.", "content": "Sodium metrizoate-ficoll separation of bovine mononuclear cells from peripheral blood yielded a granulocyte-free leukocyte population with an average recovery of 76%. A high proportion of the separated cells were of large size and monocytoid in appearance. This cell type was observed in a much smaller percentage in mononuclear preparations separated from defibrinated blood.", "contents": "Large monocytoid cell in mononuclear cell fraction of bovine blood. Sodium metrizoate-ficoll separation of bovine mononuclear cells from peripheral blood yielded a granulocyte-free leukocyte population with an average recovery of 76%. A high proportion of the separated cells were of large size and monocytoid in appearance. This cell type was observed in a much smaller percentage in mononuclear preparations separated from defibrinated blood."} {"id": "PMID:1259226", "title": "Phenotypic differences in female Ostertagia circumcincta as demonstrated by isozymes hydrolyzing alpha-naphthyl acetate.", "content": "According to results of disc gel electrophoresis of homogenates prepared from individual female nematodes of the species Ostertagia circumcincta and subsequent staining of gel preparations, a maximum of 5 isozymes, hydrolyzing alpha-naphthyl acetate, were present. On the basis of resolution and mobility, these isozymes could be classified as 2 slow and 3 fast bands. Phenotypic differences were observed in the intensity of individual bands, as well as in the presence (or absence) of bands.", "contents": "Phenotypic differences in female Ostertagia circumcincta as demonstrated by isozymes hydrolyzing alpha-naphthyl acetate. According to results of disc gel electrophoresis of homogenates prepared from individual female nematodes of the species Ostertagia circumcincta and subsequent staining of gel preparations, a maximum of 5 isozymes, hydrolyzing alpha-naphthyl acetate, were present. On the basis of resolution and mobility, these isozymes could be classified as 2 slow and 3 fast bands. Phenotypic differences were observed in the intensity of individual bands, as well as in the presence (or absence) of bands."} {"id": "PMID:1259227", "title": "Isolation and metabolism cage system for newborn pigs.", "content": "An isolation system was designed and constructed for isolating normal and infected newborn pigs. The system consisted of an outer cage fitted with a biological diffusion filter and a dunk bath entry system and an inner metabolism cage to contain the pig. When tested with S-13 bacteriophage, the isolation and metabolism cage system was at least 99% efficient in preventing the entry or escape of microorganism. A total of 267 Escherichia coli-infected newborn pigs have been isolated in these units, with no cross contaminations.", "contents": "Isolation and metabolism cage system for newborn pigs. An isolation system was designed and constructed for isolating normal and infected newborn pigs. The system consisted of an outer cage fitted with a biological diffusion filter and a dunk bath entry system and an inner metabolism cage to contain the pig. When tested with S-13 bacteriophage, the isolation and metabolism cage system was at least 99% efficient in preventing the entry or escape of microorganism. A total of 267 Escherichia coli-infected newborn pigs have been isolated in these units, with no cross contaminations."} {"id": "PMID:1259228", "title": "Erythropoiesis and erythrocytic survival in dogs with cyclic hematopoiesis.", "content": "Erythrocytic survival and ferrokinetic studies were carried out in dogs with cyclic hematopoiesis. The serum iron values varied during different phases of the cycle. The highest values occurred when the bone marrow predominantly contained granulocytic cells. The erythrocytic survival and the remainder of the ferrokinetic variables were comparable to those in normal dogs of a similar age.", "contents": "Erythropoiesis and erythrocytic survival in dogs with cyclic hematopoiesis. Erythrocytic survival and ferrokinetic studies were carried out in dogs with cyclic hematopoiesis. The serum iron values varied during different phases of the cycle. The highest values occurred when the bone marrow predominantly contained granulocytic cells. The erythrocytic survival and the remainder of the ferrokinetic variables were comparable to those in normal dogs of a similar age."} {"id": "PMID:1259229", "title": "Effect of monensin on experimental infections of Eimeria ninakohlyakimovae in lambs.", "content": "Two nearly identical experiments were conducted to determine the effects of the coccidiostatic compound monensin on Polled Dorset lambs experimentally infected with oocysts of Eimeria ninakohlyakimovae. Prophylactic medication at a dose level of 1 mg/kg of body weight was started 2 days before inoculation and prevented diarrhea and reduced oocyst production. Therapeutic medication at a dose level of 2 mg/kg, started with the appearance of signs of infection, reduced oocyst production below that of nonmedicated controls but did not eliminate diarrhea. Weight gains of medicated lambs were less than those of noninoculated, nonmedicated controls in both experiments. Apparently monensin, at the dose levels used, reduced oocyst production but also prevented weight gains as high as those in inoculated nonmedicated controls.", "contents": "Effect of monensin on experimental infections of Eimeria ninakohlyakimovae in lambs. Two nearly identical experiments were conducted to determine the effects of the coccidiostatic compound monensin on Polled Dorset lambs experimentally infected with oocysts of Eimeria ninakohlyakimovae. Prophylactic medication at a dose level of 1 mg/kg of body weight was started 2 days before inoculation and prevented diarrhea and reduced oocyst production. Therapeutic medication at a dose level of 2 mg/kg, started with the appearance of signs of infection, reduced oocyst production below that of nonmedicated controls but did not eliminate diarrhea. Weight gains of medicated lambs were less than those of noninoculated, nonmedicated controls in both experiments. Apparently monensin, at the dose levels used, reduced oocyst production but also prevented weight gains as high as those in inoculated nonmedicated controls."} {"id": "PMID:1259230", "title": "Cystine aminopeptidase activity (oxytocinase) in pregnant guinea pigs: normal and infected with Campylobacter fetus.", "content": "The cystine aminopeptidase (CAP) activity was determined in plasma from guinea pigs at various stages of gestation and in pregnant guinea pigs infected with Campylobacter fetus subspecies intestinalis. The CAP activity decreased with length of gestation, which is in contrast to the changes in activity in persons. Infected guinea pigs near the time of abortion can be distinguished from normal guinea pigs on the basis of plasma CAP activity, if the plasma samples are taken 1 to 2 days before abortion. Among pregnant guinea pigs at the same stage of gestation, CAP activity was lower for infected than for normal pregnant animals. This test might be used to indicate probable disruption of placentation and the onset of abortion in the guinea pig.", "contents": "Cystine aminopeptidase activity (oxytocinase) in pregnant guinea pigs: normal and infected with Campylobacter fetus. The cystine aminopeptidase (CAP) activity was determined in plasma from guinea pigs at various stages of gestation and in pregnant guinea pigs infected with Campylobacter fetus subspecies intestinalis. The CAP activity decreased with length of gestation, which is in contrast to the changes in activity in persons. Infected guinea pigs near the time of abortion can be distinguished from normal guinea pigs on the basis of plasma CAP activity, if the plasma samples are taken 1 to 2 days before abortion. Among pregnant guinea pigs at the same stage of gestation, CAP activity was lower for infected than for normal pregnant animals. This test might be used to indicate probable disruption of placentation and the onset of abortion in the guinea pig."} {"id": "PMID:1259235", "title": "Miliary tuberculosis in two infants after nursery exposure: epidemiologic, clinical, and laboratory findings.", "content": "Two infants born 4 days apart, and cared for in the same nursery, developed miliary tuberculosis at 2.5 and 5.5 months of age, respectively. A search for a source case among household contacts failed to reveal anyone with active tuberculosis. An epidemiologic study of nursery personnel revealed a nurse's aide with cavitary tuberculosis. Examination of 1,647 infants (98.9 per cent of all infants cared for in the nursery during the 10.5-month period preceding the discovery of the source case) failed to reveal any other infected children. Recommendations are made for tuberculosis control programs among nursery personnel that should be carefully and persistently followed.", "contents": "Miliary tuberculosis in two infants after nursery exposure: epidemiologic, clinical, and laboratory findings. Two infants born 4 days apart, and cared for in the same nursery, developed miliary tuberculosis at 2.5 and 5.5 months of age, respectively. A search for a source case among household contacts failed to reveal anyone with active tuberculosis. An epidemiologic study of nursery personnel revealed a nurse's aide with cavitary tuberculosis. Examination of 1,647 infants (98.9 per cent of all infants cared for in the nursery during the 10.5-month period preceding the discovery of the source case) failed to reveal any other infected children. Recommendations are made for tuberculosis control programs among nursery personnel that should be carefully and persistently followed."} {"id": "PMID:1259236", "title": "Ventilatory defects in atypical mycobacteriosis. A comparison study with tuberculosis.", "content": "Two hundred thirty-two patients infected with Mycobacterium kansasii and 120 patients infected with M. intracellulare who were admitted to the East Texas Chest Hospital between 1965 and 1974 were individually matched according to age (+/- 5 years), sex, and extent of disease with an equal number of patients infected with M. tuberculosis. The ventilatory function in these patients was compared. The frequency of obstructive ventilatory defect, defined as forced expiratory volume in 1 sec less than 70 per cent of forced vital capacity, was greater among M. kansasii patients (68.9 per cent of 232) than among M. tuberculosis patients less than 80 per cent of predicted, was greater among M. intracellulare patients (68.3 per cent of 120) than among M. tuberculosis patients (57.5 per cent of 120). Above age 40, obstructive ventilatory defects tended to be more common in M. kansasii patients, whereas restricted ventilatory defects tended to be more common in M. intracellulare patients when compared with the same age group of M. tuberculosis patients. As expected, ventilatory function values among the M. tuberculosis groups decreased as extent of disease increased. In contrast, among the M. kansasii and M. intracellulare groups, these values were poorly related to the extent of disease; values were relatively low even with minimal extent of disease. It is suggested that the increased ventilatory defects among the M. kansasii and M. intracellulare patients could be accounted for by coexistent lung disease.", "contents": "Ventilatory defects in atypical mycobacteriosis. A comparison study with tuberculosis. Two hundred thirty-two patients infected with Mycobacterium kansasii and 120 patients infected with M. intracellulare who were admitted to the East Texas Chest Hospital between 1965 and 1974 were individually matched according to age (+/- 5 years), sex, and extent of disease with an equal number of patients infected with M. tuberculosis. The ventilatory function in these patients was compared. The frequency of obstructive ventilatory defect, defined as forced expiratory volume in 1 sec less than 70 per cent of forced vital capacity, was greater among M. kansasii patients (68.9 per cent of 232) than among M. tuberculosis patients less than 80 per cent of predicted, was greater among M. intracellulare patients (68.3 per cent of 120) than among M. tuberculosis patients (57.5 per cent of 120). Above age 40, obstructive ventilatory defects tended to be more common in M. kansasii patients, whereas restricted ventilatory defects tended to be more common in M. intracellulare patients when compared with the same age group of M. tuberculosis patients. As expected, ventilatory function values among the M. tuberculosis groups decreased as extent of disease increased. In contrast, among the M. kansasii and M. intracellulare groups, these values were poorly related to the extent of disease; values were relatively low even with minimal extent of disease. It is suggested that the increased ventilatory defects among the M. kansasii and M. intracellulare patients could be accounted for by coexistent lung disease."} {"id": "PMID:1259237", "title": "Water as a source of potentially pathogenic mycobacteria.", "content": "The mycobacterial flora of 321 water samples was explored to evaluate the role of this part of the environment as a possible source of human mycobacterial disease. The samples included natural waters, waters treated to make them suitable for drinking, and waters in contact with animals. Water from the city aquarium contained the greatest abundance of mycobacteria, with an average of 3.5 strains per sample. The highest yield of positive cultures came from samples in contact with zoo animals and with fish. The majority of the isolated strains were slowly growing mycobacteria; 80 were Mycobacterium gordonae, and 34 of thse belong to a new serotype. Forty-seven cultures were members of the M. avian-intracellulare-scrofulaceum complex, of which 11 were typable by agglutination. From this study and from the work of others, it is concluded that water may be contaminated with potentially pathogenic mycobacteria and thus may serve as a source of human disease.", "contents": "Water as a source of potentially pathogenic mycobacteria. The mycobacterial flora of 321 water samples was explored to evaluate the role of this part of the environment as a possible source of human mycobacterial disease. The samples included natural waters, waters treated to make them suitable for drinking, and waters in contact with animals. Water from the city aquarium contained the greatest abundance of mycobacteria, with an average of 3.5 strains per sample. The highest yield of positive cultures came from samples in contact with zoo animals and with fish. The majority of the isolated strains were slowly growing mycobacteria; 80 were Mycobacterium gordonae, and 34 of thse belong to a new serotype. Forty-seven cultures were members of the M. avian-intracellulare-scrofulaceum complex, of which 11 were typable by agglutination. From this study and from the work of others, it is concluded that water may be contaminated with potentially pathogenic mycobacteria and thus may serve as a source of human disease."} {"id": "PMID:1259238", "title": "Evaluation of a temperature-sensitive influenza virus in elderly and chronically ill subjects.", "content": "A temperature-sensitive influenza virus, influenza A/Hong Kong/68-ts-1 (E), was administered to 18 elderly subjects and to 18 chronically ill subjects. Clinical reactions were infrequent (n = 3), mild, and afebrile. Vaccine virus was recovered from 5 subjects. Serum-neutralizing antibody responses to A/Hong Kong/68 antigen were detected in 13. Serum hemagglutination inhibiting antibodies were detected in 6 to A/Hong Kong/68 antigen and in 7 to A/England/42/72 antigen. Nasal antibodies were detected in 3. Using any criteria, a total of 17 patients developed evidence of infection, and occurrence of infection was related to concentration of serum antibody before inoculation. Transmission of vaccine virus may have occurred to one of 10 uninoculated subjects. In the presence of a naturally occurring outbreak of influenza A/England/42/72, 15 ts-1 (E) vaccines and 17 of 42 persons who had received parenteral vaccine became ill. Evidence of infection with influenza virus was obtained in 8 of the former and 10 of the latter group.", "contents": "Evaluation of a temperature-sensitive influenza virus in elderly and chronically ill subjects. A temperature-sensitive influenza virus, influenza A/Hong Kong/68-ts-1 (E), was administered to 18 elderly subjects and to 18 chronically ill subjects. Clinical reactions were infrequent (n = 3), mild, and afebrile. Vaccine virus was recovered from 5 subjects. Serum-neutralizing antibody responses to A/Hong Kong/68 antigen were detected in 13. Serum hemagglutination inhibiting antibodies were detected in 6 to A/Hong Kong/68 antigen and in 7 to A/England/42/72 antigen. Nasal antibodies were detected in 3. Using any criteria, a total of 17 patients developed evidence of infection, and occurrence of infection was related to concentration of serum antibody before inoculation. Transmission of vaccine virus may have occurred to one of 10 uninoculated subjects. In the presence of a naturally occurring outbreak of influenza A/England/42/72, 15 ts-1 (E) vaccines and 17 of 42 persons who had received parenteral vaccine became ill. Evidence of infection with influenza virus was obtained in 8 of the former and 10 of the latter group."} {"id": "PMID:1259239", "title": "The effect of acute, intensive cigarette smoking on maximal expiratory flows and the single-breath nitrogen washout trace.", "content": "The effect of acute, intensive cigarette smoking on forced vital capacity and the single-breath expired N2 trace was studied in 82 smokers. There were significant decreases in the \"effort-dependent\" tests, such as peak flow and 1-sec forced expiratory volume, but no change in the more \"effort-independent\" tests, such as maximal mid-expiratory flow and maximal expiratory flow at 25 per cent of the vital capacity. Closing volume was unchanged in absolute terms and as a percentage of vital capacity. Closing capacity was unchanged in absolute terms and as a percentage of total lung capacity, but there was a significant increase in the slope of Phase III of the N2 washout curve after the acute smoking session. The tests of function that changed significantly after acute, intensive smoking were the ones that improved in 52 subjects who modified their smoking habits. The data suggest that acute, intensive cigarette smoking may be associated with an increase in resistance to air flow in the larger airways or a reduction in effort, and with increased nonuniformity of intraregional distribution of ventilation.", "contents": "The effect of acute, intensive cigarette smoking on maximal expiratory flows and the single-breath nitrogen washout trace. The effect of acute, intensive cigarette smoking on forced vital capacity and the single-breath expired N2 trace was studied in 82 smokers. There were significant decreases in the \"effort-dependent\" tests, such as peak flow and 1-sec forced expiratory volume, but no change in the more \"effort-independent\" tests, such as maximal mid-expiratory flow and maximal expiratory flow at 25 per cent of the vital capacity. Closing volume was unchanged in absolute terms and as a percentage of vital capacity. Closing capacity was unchanged in absolute terms and as a percentage of total lung capacity, but there was a significant increase in the slope of Phase III of the N2 washout curve after the acute smoking session. The tests of function that changed significantly after acute, intensive smoking were the ones that improved in 52 subjects who modified their smoking habits. The data suggest that acute, intensive cigarette smoking may be associated with an increase in resistance to air flow in the larger airways or a reduction in effort, and with increased nonuniformity of intraregional distribution of ventilation."} {"id": "PMID:1259240", "title": "Relationship of constitutional factors and cigarette smoking to decrease in 1-second forced expiratory volume.", "content": "A 5-year prospective survey of 34 subjects with mild chronic bronchitis revealed marked individual variation in the annual rate of decrease in the forced expiratory volume in 1 sec. The mean annual decrease in the 1-sec forced expiratory volume was 0.046 +/- 0.057 liter. Although the annual decrease in the 1-sec forced expiratory volume was greater among smokers (0.056 +/- 0.061 liter per year) than non- and ex-smokers (0.016 +/- 0.021 liter per year; P less than 0.005), differences in tobacco consumption did not account for the individual variation. This variation was related, instead, to 3 phenomena believed to indicate the presence of host susceptibility to chronic bronchitis. These phenomena were bronchial reactivity to methacholine, ventilatory responsiveness to isoproterenol, and sputum eosinophilia. The correlation between the rate of decrease in 1-sec forced expiratory volume and the degree of methacholine reactivity was 0.76 (P less than 0.001); the correlation between the decrease in 1-sec forced expiratory volume and ventilatory responsoveness to isoproterenol was 0.45 (P less than 0.01). Deterioration of 1-sec forced expiratory volume was appreciably greater among those with sputum eosinophilia (0.062 +/- 0.06 liter per year) than among thse without eosinophilia (0.017 +/- 0.033 liter per year P less than 0.01). The progression of abnormality appeared to depend on an interaction between cigarette smoking and individual susceptibility. Even minimal tobacco consumption led to serious ventilatory deterioration when methacholine reactivity was high, whereas heavy smoking produced little effect on the decrease in 1-sec forced expiratory volume when methacholine reactivity was slight.", "contents": "Relationship of constitutional factors and cigarette smoking to decrease in 1-second forced expiratory volume. A 5-year prospective survey of 34 subjects with mild chronic bronchitis revealed marked individual variation in the annual rate of decrease in the forced expiratory volume in 1 sec. The mean annual decrease in the 1-sec forced expiratory volume was 0.046 +/- 0.057 liter. Although the annual decrease in the 1-sec forced expiratory volume was greater among smokers (0.056 +/- 0.061 liter per year) than non- and ex-smokers (0.016 +/- 0.021 liter per year; P less than 0.005), differences in tobacco consumption did not account for the individual variation. This variation was related, instead, to 3 phenomena believed to indicate the presence of host susceptibility to chronic bronchitis. These phenomena were bronchial reactivity to methacholine, ventilatory responsiveness to isoproterenol, and sputum eosinophilia. The correlation between the rate of decrease in 1-sec forced expiratory volume and the degree of methacholine reactivity was 0.76 (P less than 0.001); the correlation between the decrease in 1-sec forced expiratory volume and ventilatory responsoveness to isoproterenol was 0.45 (P less than 0.01). Deterioration of 1-sec forced expiratory volume was appreciably greater among those with sputum eosinophilia (0.062 +/- 0.06 liter per year) than among thse without eosinophilia (0.017 +/- 0.033 liter per year P less than 0.01). The progression of abnormality appeared to depend on an interaction between cigarette smoking and individual susceptibility. Even minimal tobacco consumption led to serious ventilatory deterioration when methacholine reactivity was high, whereas heavy smoking produced little effect on the decrease in 1-sec forced expiratory volume when methacholine reactivity was slight."} {"id": "PMID:1259241", "title": "Mechanisms of maximal expiratory flow limitation in clinically unsuspected emphysema and obstruction of the peripheral airways.", "content": "We studied the determinants of maximal expiratory flow in 7 patients in whom surgical lung specimens showed evidence of mild emphysema or obstruction of the peripheral airways. All the patients showed frequency dependence of dynamic lung compliance and low maximal expiratory flow. Lung elastic recoil pressures were reduced at all lung volumes in 4 of 5 patients with emphysema but were normal in 2 patients with obstruction of the peripheral airways. Maximal flow-static recoil curves showed a high intercept in the pressure axis when the slope between 50 per cent and 30 per cent of vital capacity was extrapolated to zero flow (transmural pressure in the flow-limiting segment) in all patients. The slope of these curve represents the conductance of the segment that extends from the alveoli to the flow-limiting segment and includes the latter. Conductance of this segment was higher than normal in 4 patients with emphysema and borderline low in one, and low in one patient with obstruction of the peripheral airways and borderline low in the other. Increased transmural pressure in the flow-limiting segment was interpreted as being due to peripheral location of collapsible flow-limiting segment and, in part, limiting maximal expiratory flow. The results also suggested that flow limitation in emphysema may occur without physiologic evidence of increased resistance of peripheral airways when, in fact, bronchiolitis is present on histologic examination.", "contents": "Mechanisms of maximal expiratory flow limitation in clinically unsuspected emphysema and obstruction of the peripheral airways. We studied the determinants of maximal expiratory flow in 7 patients in whom surgical lung specimens showed evidence of mild emphysema or obstruction of the peripheral airways. All the patients showed frequency dependence of dynamic lung compliance and low maximal expiratory flow. Lung elastic recoil pressures were reduced at all lung volumes in 4 of 5 patients with emphysema but were normal in 2 patients with obstruction of the peripheral airways. Maximal flow-static recoil curves showed a high intercept in the pressure axis when the slope between 50 per cent and 30 per cent of vital capacity was extrapolated to zero flow (transmural pressure in the flow-limiting segment) in all patients. The slope of these curve represents the conductance of the segment that extends from the alveoli to the flow-limiting segment and includes the latter. Conductance of this segment was higher than normal in 4 patients with emphysema and borderline low in one, and low in one patient with obstruction of the peripheral airways and borderline low in the other. Increased transmural pressure in the flow-limiting segment was interpreted as being due to peripheral location of collapsible flow-limiting segment and, in part, limiting maximal expiratory flow. The results also suggested that flow limitation in emphysema may occur without physiologic evidence of increased resistance of peripheral airways when, in fact, bronchiolitis is present on histologic examination."} {"id": "PMID:1259242", "title": "Removal of endobronchial foreign body by fiberoptic bronchoscopy.", "content": "A relatively large foreign body (ham bone) was seen in the left upper lobe bronchus of a 25-year-old woman and was successfully extracted with the use of a standard fiberoptic bronchoscope. Although the removal of foreign bodies by the fiberoptic bronchoscope has serious technical limitations, the use of this instrument should be considered when the foreign body is not within range of the rigid bronchoscope.", "contents": "Removal of endobronchial foreign body by fiberoptic bronchoscopy. A relatively large foreign body (ham bone) was seen in the left upper lobe bronchus of a 25-year-old woman and was successfully extracted with the use of a standard fiberoptic bronchoscope. Although the removal of foreign bodies by the fiberoptic bronchoscope has serious technical limitations, the use of this instrument should be considered when the foreign body is not within range of the rigid bronchoscope."} {"id": "PMID:1259243", "title": "Observations of the pathology of clubbed fingers with special reference to mast cells.", "content": "Mast cell counts were made, in tissue samples of normal and clubbed fingers obtained at autopsy, to investigate the possibility that mast cells act as an intermediary in the development of finger clubbing. Quantitative measurements of the composition of the tissues of the normal and clubbed nail bed were also made. The only significant difference in mast cell numbers in clubbed fingers was a decrease in mast cells in the tissues just superficial to the nail. The appearance of the mast cells was normal. The porportion of blood vessels and other tissues was not significantly different from normal.", "contents": "Observations of the pathology of clubbed fingers with special reference to mast cells. Mast cell counts were made, in tissue samples of normal and clubbed fingers obtained at autopsy, to investigate the possibility that mast cells act as an intermediary in the development of finger clubbing. Quantitative measurements of the composition of the tissues of the normal and clubbed nail bed were also made. The only significant difference in mast cell numbers in clubbed fingers was a decrease in mast cells in the tissues just superficial to the nail. The appearance of the mast cells was normal. The porportion of blood vessels and other tissues was not significantly different from normal."} {"id": "PMID:1259244", "title": "A study of a new bronchodilator: carbuterol.", "content": "A new oral bronchodilator, carbuterol, was studied in 9 subjects who had reversible airway obstruction. In addition to the spirometric changes, serial arterial blood gas determinations were done to see if the drug induced hypoxemia. Two- and 4-mg doses were compared with the placebo. There was a significant bronchodilating effect with the 4-mg dose beginning 30 min after administration of the drug. Maximal improvement of forced expiratory volume in 1 sec was observed at 4 hours, with a 42 per cent increase from the baseline. No significant hypoxemia was observed. The drug was considered an effective bronchodilating agent, with the effect lasting longer than 4 hours.", "contents": "A study of a new bronchodilator: carbuterol. A new oral bronchodilator, carbuterol, was studied in 9 subjects who had reversible airway obstruction. In addition to the spirometric changes, serial arterial blood gas determinations were done to see if the drug induced hypoxemia. Two- and 4-mg doses were compared with the placebo. There was a significant bronchodilating effect with the 4-mg dose beginning 30 min after administration of the drug. Maximal improvement of forced expiratory volume in 1 sec was observed at 4 hours, with a 42 per cent increase from the baseline. No significant hypoxemia was observed. The drug was considered an effective bronchodilating agent, with the effect lasting longer than 4 hours."} {"id": "PMID:1259247", "title": "Biliary ascariasis.", "content": "Biliary ascariasis, rarely noted in the western literature, is a common condition in other climates. An increase in infestation may occur with travel to these countries. With the changes in biliary function which follow common duct exploration, invasion can occur in the affected individual. Treatment involves antispasmodics, antihelminthetics, and prevention of superinfection. Surgical intervention is reserved for specific indications of failure of medical therapy.", "contents": "Biliary ascariasis. Biliary ascariasis, rarely noted in the western literature, is a common condition in other climates. An increase in infestation may occur with travel to these countries. With the changes in biliary function which follow common duct exploration, invasion can occur in the affected individual. Treatment involves antispasmodics, antihelminthetics, and prevention of superinfection. Surgical intervention is reserved for specific indications of failure of medical therapy."} {"id": "PMID:1259248", "title": "Carcinoma of the pancreas.", "content": "Study of hospital records of 146 patients with carcinoma of the pancreas from 1952 to 1971 revealed that 74 per cent had had abdominal pain and 65 per cent jaundice. Abdominal pain was the commonest symptom of carcinoma of the head as well as of the body and tail. Diabetes mellitus was four times as common among the patients with carcinoma of the pancreas as among the population in general. The interval between the onset of symptoms and diagnosis of the disease was the same in both decades of the 20-year period, but the survival time after operation was longer in the second 10-year period. Pancreatoduodenectomy was possible in only four of the 138 patients operated on, and one of them died postoperatively. The three patients who survived the operation survived significantly longer than the 87 in whom an anastomosis had been established between the bile ducts and the intestine. Forty-one patients were subjected to surgical exploration only. No difference in survival time was found between the two last-mentioned groups.", "contents": "Carcinoma of the pancreas. Study of hospital records of 146 patients with carcinoma of the pancreas from 1952 to 1971 revealed that 74 per cent had had abdominal pain and 65 per cent jaundice. Abdominal pain was the commonest symptom of carcinoma of the head as well as of the body and tail. Diabetes mellitus was four times as common among the patients with carcinoma of the pancreas as among the population in general. The interval between the onset of symptoms and diagnosis of the disease was the same in both decades of the 20-year period, but the survival time after operation was longer in the second 10-year period. Pancreatoduodenectomy was possible in only four of the 138 patients operated on, and one of them died postoperatively. The three patients who survived the operation survived significantly longer than the 87 in whom an anastomosis had been established between the bile ducts and the intestine. Forty-one patients were subjected to surgical exploration only. No difference in survival time was found between the two last-mentioned groups."} {"id": "PMID:1259250", "title": "Effective surgical palliation of giant compressive bullous emphysema (vanishing lung syndrome): long-term follow-up.", "content": "Giant compressive bullous emphysema is rare. The three major considerations for operation involve a breathless patient with giant bullae occupying more than one-third of one lung field who has a positive pulmonary arteriogram revealing diminished blood flow to the involved lung. Finally, we think that the survivors in our series, eight long-term postoperative patients alive one year to 14 years, supply gratifying evidence that surgery can provide effective and safe palliation.", "contents": "Effective surgical palliation of giant compressive bullous emphysema (vanishing lung syndrome): long-term follow-up. Giant compressive bullous emphysema is rare. The three major considerations for operation involve a breathless patient with giant bullae occupying more than one-third of one lung field who has a positive pulmonary arteriogram revealing diminished blood flow to the involved lung. Finally, we think that the survivors in our series, eight long-term postoperative patients alive one year to 14 years, supply gratifying evidence that surgery can provide effective and safe palliation."} {"id": "PMID:1259251", "title": "A combined surgical approach in the management of achalasia of the esophagus.", "content": "The treatment of achalasia at the present time is far from being ideal. The results of pneumatic dilatation have not always been impressive and the risk of esophageal perforation is real. Modified Heller operation has succeded in relieving obstructive symptoms in the majority of patients with achalasia. However, the reported incidence of reflux esophagitis following Heller myotomy is four to 37 per cent. In 25 patients with achalasia followed up to 10 years after Heller myotomy, nine patients had symptomatic reflux and three patients developed esophageal strictures. We believe the addition of an anti-reflux operation should be considered in all patients undergoing operation for achalasia and especially those patients with preoperative symptoms of reflux.", "contents": "A combined surgical approach in the management of achalasia of the esophagus. The treatment of achalasia at the present time is far from being ideal. The results of pneumatic dilatation have not always been impressive and the risk of esophageal perforation is real. Modified Heller operation has succeded in relieving obstructive symptoms in the majority of patients with achalasia. However, the reported incidence of reflux esophagitis following Heller myotomy is four to 37 per cent. In 25 patients with achalasia followed up to 10 years after Heller myotomy, nine patients had symptomatic reflux and three patients developed esophageal strictures. We believe the addition of an anti-reflux operation should be considered in all patients undergoing operation for achalasia and especially those patients with preoperative symptoms of reflux."} {"id": "PMID:1259252", "title": "Duodenal varices.", "content": "Upper gastrointestinal bleeding from isolated duodenal varices is a rare occurrence. We report the case of a patient with idiopathic duodenal varices in whom the diagnosis was established preoperatively by endoscopy. The patient did not have esophageal varices or portal hypertension, and he was treated by exicising the varix with a full thickness of duodenal wall. Bleeding has not recurred. Duodenal varices as well as duodenal ulcer and gastritis must be considered in evaluating a patient with cirrhosis and upper gastrointestinal bleeding.", "contents": "Duodenal varices. Upper gastrointestinal bleeding from isolated duodenal varices is a rare occurrence. We report the case of a patient with idiopathic duodenal varices in whom the diagnosis was established preoperatively by endoscopy. The patient did not have esophageal varices or portal hypertension, and he was treated by exicising the varix with a full thickness of duodenal wall. Bleeding has not recurred. Duodenal varices as well as duodenal ulcer and gastritis must be considered in evaluating a patient with cirrhosis and upper gastrointestinal bleeding."} {"id": "PMID:1259253", "title": "Mobile cecal syndrome in the adult.", "content": "The mobile cecal syndrome is primarily a disease of children. However, it may be present as a precursor of frank cecal volvulus in approximately 50 per cent of the cases. Symptoms are intermittent colicky right lower quadrant pain with tenderness over McBurney's point and hyperactive high-pitched bowel sounds during the attack. After the attack, the patient is asymptomatic. Three cases of young women with mobile cecal syndrome are presented to illustrate the clinical course and surgical therapy. The mobile cecal syndrome should be considered in the differential diagnosis of right lower quadrant pain from obscure causes.", "contents": "Mobile cecal syndrome in the adult. The mobile cecal syndrome is primarily a disease of children. However, it may be present as a precursor of frank cecal volvulus in approximately 50 per cent of the cases. Symptoms are intermittent colicky right lower quadrant pain with tenderness over McBurney's point and hyperactive high-pitched bowel sounds during the attack. After the attack, the patient is asymptomatic. Three cases of young women with mobile cecal syndrome are presented to illustrate the clinical course and surgical therapy. The mobile cecal syndrome should be considered in the differential diagnosis of right lower quadrant pain from obscure causes."} {"id": "PMID:1259254", "title": "Perineal wound healing after abdominoperineal resection.", "content": "The healing of the perineal wound after proctectomy depends on the disease, the presence of perianal infection, and the technique of management of the perineum. Experience shows that when the perineum is left open, healing by secondary intention is accompanied by a significant morbidity, extended hospitalization, continued disability, prolonged postoperative drainage and an occasional persistent perineal sinus. The patients required daily care of the perineum for two to 12 months. The wound healed slower in patients with inflammatory disease of the colon. Within six months the perineum healed in 58 per cent of the patients with inflammatory disease and 70 per cent of the patients with carcinoma. After one year, healing had taken place in 98 per cent of the patients. It is necessary to leave the perineal wound open in the patients with perineal sepsis, contamination and uncontrollable hemorrhage. For the other patients, there should be some attempt to close the perineum and obtain primary healing of the wound.", "contents": "Perineal wound healing after abdominoperineal resection. The healing of the perineal wound after proctectomy depends on the disease, the presence of perianal infection, and the technique of management of the perineum. Experience shows that when the perineum is left open, healing by secondary intention is accompanied by a significant morbidity, extended hospitalization, continued disability, prolonged postoperative drainage and an occasional persistent perineal sinus. The patients required daily care of the perineum for two to 12 months. The wound healed slower in patients with inflammatory disease of the colon. Within six months the perineum healed in 58 per cent of the patients with inflammatory disease and 70 per cent of the patients with carcinoma. After one year, healing had taken place in 98 per cent of the patients. It is necessary to leave the perineal wound open in the patients with perineal sepsis, contamination and uncontrollable hemorrhage. For the other patients, there should be some attempt to close the perineum and obtain primary healing of the wound."} {"id": "PMID:1259256", "title": "Tetanus in a patient with a uterine tumor.", "content": "A 45-year-old woman developed tetanus in a necrotic 5 Kg leiomyoma of the uterus; she was treated successfully by a combined surgical and anesthesiology team. A hysterectomy was performed despite the considerable controversy in the older publications. This literature was reviewed, and it was noted that there have been only two previously published cases of uterine tetanus other than in a post-abortal situation. The practical aspects of the management of severe tetanus are tabulated.", "contents": "Tetanus in a patient with a uterine tumor. A 45-year-old woman developed tetanus in a necrotic 5 Kg leiomyoma of the uterus; she was treated successfully by a combined surgical and anesthesiology team. A hysterectomy was performed despite the considerable controversy in the older publications. This literature was reviewed, and it was noted that there have been only two previously published cases of uterine tetanus other than in a post-abortal situation. The practical aspects of the management of severe tetanus are tabulated."} {"id": "PMID:1259257", "title": "Serum lipid levels in angiographically defined coronary artery disease.", "content": "To evaluate the association between serum cholesterol and triglyceride levels and angiographically determined coronary artery disease, two selected groups of 100 patients each were compared. The coronary artery disease group had significantly higher serum levels of both cholesterol and triglyceride. However, several types of analyses based on the quartile distribution of serum levels of cholesterol and triglyceride showed that the serum cholesterol level was more significantly associated with coronary artery disease than was the triglyceride level. This was especially true in relation to multivessel disease, the most severe form of coronary artery disease, and most marked in men. Association with coronary artery disease appeared to be continuous, rather than being related to any critical serum level, thus re-emphasizing the need to distinguish between desirable and average levels of serum cholesterol in countries with a high dietary intake of saturated fat.", "contents": "Serum lipid levels in angiographically defined coronary artery disease. To evaluate the association between serum cholesterol and triglyceride levels and angiographically determined coronary artery disease, two selected groups of 100 patients each were compared. The coronary artery disease group had significantly higher serum levels of both cholesterol and triglyceride. However, several types of analyses based on the quartile distribution of serum levels of cholesterol and triglyceride showed that the serum cholesterol level was more significantly associated with coronary artery disease than was the triglyceride level. This was especially true in relation to multivessel disease, the most severe form of coronary artery disease, and most marked in men. Association with coronary artery disease appeared to be continuous, rather than being related to any critical serum level, thus re-emphasizing the need to distinguish between desirable and average levels of serum cholesterol in countries with a high dietary intake of saturated fat."} {"id": "PMID:1259258", "title": "Atrial septal defect: echocardiographic observations. Studies in 120 patients.", "content": "Previous studies on small numbers of patients have indicated a high incidence of increased right ventricular dimension and abnormal ventricular septal motion in patients with atrial septal defect. However, recent evidence suggests that septal motion may be normal in as many as 46% of patients with atrial septal defect when observed at proper levels. We have analyzed the echocardiograms of 120 patients with sinus venosus or secundum atrial septal defect in an attempt to define sensitivity of the foregoing two echocardiographic abnormalities. Right ventricular dimension index was increased in 98% of patients. When both sides of the ventricular septum were analyzed, abnormal ventricular septal motion was observed in 87% of patients. It is important to observe both right and left septal echoes at all levels. Other measurements and observations were made when possible and are included in the study.", "contents": "Atrial septal defect: echocardiographic observations. Studies in 120 patients. Previous studies on small numbers of patients have indicated a high incidence of increased right ventricular dimension and abnormal ventricular septal motion in patients with atrial septal defect. However, recent evidence suggests that septal motion may be normal in as many as 46% of patients with atrial septal defect when observed at proper levels. We have analyzed the echocardiograms of 120 patients with sinus venosus or secundum atrial septal defect in an attempt to define sensitivity of the foregoing two echocardiographic abnormalities. Right ventricular dimension index was increased in 98% of patients. When both sides of the ventricular septum were analyzed, abnormal ventricular septal motion was observed in 87% of patients. It is important to observe both right and left septal echoes at all levels. Other measurements and observations were made when possible and are included in the study."} {"id": "PMID:1259259", "title": "Pneumococcal pneumonia: capsular polysaccharide antigenemia and antibody responses.", "content": "Capsular polysaccharide was detected in the serum in 19 of 46 patients with pneumococcal pneumonia. Antigenemia was strongly associated with bacteremia and with infection by low-numbered serotypes. During antibiotic therapy, the concentration of polysaccharide in the circulation declined progressively, but circulating antigen remained detectable in two thirds of cases for 2 weeks or longer. The development of measurable type-specific antibody was delayed in patients with antigenemia. It is not known whether this delay was due to diminished antibody production or to neutralization of antibody by circulating antigen. Despite effective antibiotic therapy many patients with antigenemia had a severe and protracted illness; this may have been related to diminished availability of antibody early in the infection.", "contents": "Pneumococcal pneumonia: capsular polysaccharide antigenemia and antibody responses. Capsular polysaccharide was detected in the serum in 19 of 46 patients with pneumococcal pneumonia. Antigenemia was strongly associated with bacteremia and with infection by low-numbered serotypes. During antibiotic therapy, the concentration of polysaccharide in the circulation declined progressively, but circulating antigen remained detectable in two thirds of cases for 2 weeks or longer. The development of measurable type-specific antibody was delayed in patients with antigenemia. It is not known whether this delay was due to diminished antibody production or to neutralization of antibody by circulating antigen. Despite effective antibiotic therapy many patients with antigenemia had a severe and protracted illness; this may have been related to diminished availability of antibody early in the infection."} {"id": "PMID:1259260", "title": "The prevalence of tuberculosis and positive tuberculin skin tests in a steroid-treated asthmatic population.", "content": "The prevalence of active tuberculosis and positive tuberculin skin tests was assessed in 132 corticosteroid-treated asthmatics for an evaluation period that represented 620 corticosteroid-years of therapy. There was no evidence of active tuberculosis in any of these patients. Positive intermediate-strength tuberculin tests were present in 28% of patients and correlated with increased age. In patients treated with daily corticosteroids, tuberculin negativity was associated with a higher dose of corticosteroids. Positive second-strength tuberculin tests were found in 42.3% of the patients with negative intermediate-strength tests and also correlated with increased age. Based on these data as well as the prevalence of significant liver disease in older patients receiving isoniazid (INH), routine INH chemoprophylaxis for corticosteroid-treated asthmatic patients, regardless of their tuberculin cutaneous reactivity, is not indicated.", "contents": "The prevalence of tuberculosis and positive tuberculin skin tests in a steroid-treated asthmatic population. The prevalence of active tuberculosis and positive tuberculin skin tests was assessed in 132 corticosteroid-treated asthmatics for an evaluation period that represented 620 corticosteroid-years of therapy. There was no evidence of active tuberculosis in any of these patients. Positive intermediate-strength tuberculin tests were present in 28% of patients and correlated with increased age. In patients treated with daily corticosteroids, tuberculin negativity was associated with a higher dose of corticosteroids. Positive second-strength tuberculin tests were found in 42.3% of the patients with negative intermediate-strength tests and also correlated with increased age. Based on these data as well as the prevalence of significant liver disease in older patients receiving isoniazid (INH), routine INH chemoprophylaxis for corticosteroid-treated asthmatic patients, regardless of their tuberculin cutaneous reactivity, is not indicated."} {"id": "PMID:1259261", "title": "Polyneuropathy and anasarca: evidence for a new connective-tissue syndrome and vasculopathic contribution.", "content": "A 41-year-old woman manifested a polyneuropathy, anasarca, pseudotumor cerebri, hyperhidrosis and hyperpigmentation of the skin, generalized lymphadenopathy, distal esophageal dysphagia, pleuritis, platelike pulmonary atelectasis, fluctuating renal insufficiency, hepatosplenomegaly, amenorrhea, and slight fever suggesting a connective-tissue disorder. Extensive clinical and laboratory evaluation did not support the initial impression of progressive systemic sclerosis or systemic lupus erythematosus but did show nonnecrotizing vascular changes, mild polyclonal gammopathy, and low thyroxin levels similar to the syndrome of polyneuropathy and endocrine disturbances recently reported from Japan. The impressive response to moderate-dose corticosteroids and exacerbation on withdrawal require diagnostic awareness of this insidiously progressive multisystem disorder. A bland vasculopathic process resulting from metabolic or immunologic disturbances appears to be the best explanation for this new syndrome, which has previously been recognized only in Japan.", "contents": "Polyneuropathy and anasarca: evidence for a new connective-tissue syndrome and vasculopathic contribution. A 41-year-old woman manifested a polyneuropathy, anasarca, pseudotumor cerebri, hyperhidrosis and hyperpigmentation of the skin, generalized lymphadenopathy, distal esophageal dysphagia, pleuritis, platelike pulmonary atelectasis, fluctuating renal insufficiency, hepatosplenomegaly, amenorrhea, and slight fever suggesting a connective-tissue disorder. Extensive clinical and laboratory evaluation did not support the initial impression of progressive systemic sclerosis or systemic lupus erythematosus but did show nonnecrotizing vascular changes, mild polyclonal gammopathy, and low thyroxin levels similar to the syndrome of polyneuropathy and endocrine disturbances recently reported from Japan. The impressive response to moderate-dose corticosteroids and exacerbation on withdrawal require diagnostic awareness of this insidiously progressive multisystem disorder. A bland vasculopathic process resulting from metabolic or immunologic disturbances appears to be the best explanation for this new syndrome, which has previously been recognized only in Japan."} {"id": "PMID:1259262", "title": "Observations on decreased serum glutamic oxalacetic transaminase (SGOT) activity in azotemic patients.", "content": "Serum glutamic oxalacetic transaminase (SGOT) activity may be decreased or even absent in patients with uremia. We correlated urea concentration with SGOT activity by the automated Rush (AutoAnalyzer, Techicon Instruments Corp., Tarrytown, New York) method (SGOT, SMA) and by the Henry-Karmen kinetic assay (SGOT, K). Extremely low SGOT (SMA) activity (less than 10 IU) was found in 6% of 5030 consecutive samples, and 71% of them occurred in patients with azotemia. SGOT activity was inversely proportional to urea concentration. A similar but less obvious pattern was observed with the SGOT (K) assay. SGOT activity increased significantly after hemodialysis in a group of 16 patients studied by both methods. It was not inhibited either by urea or uremic serum added in vitro. The explanation for this phenomenon is not known.", "contents": "Observations on decreased serum glutamic oxalacetic transaminase (SGOT) activity in azotemic patients. Serum glutamic oxalacetic transaminase (SGOT) activity may be decreased or even absent in patients with uremia. We correlated urea concentration with SGOT activity by the automated Rush (AutoAnalyzer, Techicon Instruments Corp., Tarrytown, New York) method (SGOT, SMA) and by the Henry-Karmen kinetic assay (SGOT, K). Extremely low SGOT (SMA) activity (less than 10 IU) was found in 6% of 5030 consecutive samples, and 71% of them occurred in patients with azotemia. SGOT activity was inversely proportional to urea concentration. A similar but less obvious pattern was observed with the SGOT (K) assay. SGOT activity increased significantly after hemodialysis in a group of 16 patients studied by both methods. It was not inhibited either by urea or uremic serum added in vitro. The explanation for this phenomenon is not known."} {"id": "PMID:1259263", "title": "1-alphahydroxycholecalciferol in chronic renal failure. Studies of the effect or oral doses.", "content": "Four patients with advanced chronic renal failure and osteodystrophy were treated with 1-alphahydroxycholecalciferol, a synthetic vitamin D analogue, in a daily oral dose of 1.5 to 2.0 mug, for periods up to 1 year. They showed increased calcium absorption, positive calcium and phosphorus balances, moderate increases in serum calcium levels, marked reductions in serum alkaline phosphatase levels, a decrease in serum immunoreactive parathyroid hormone levels, and radiologic and histologic improvement in bone disease. One patient with proximal myopathy showed improvement in muscular strength. 1-Alphahydroxycholecalciferol appears to be effective therapy for renal osteodystrophy.", "contents": "1-alphahydroxycholecalciferol in chronic renal failure. Studies of the effect or oral doses. Four patients with advanced chronic renal failure and osteodystrophy were treated with 1-alphahydroxycholecalciferol, a synthetic vitamin D analogue, in a daily oral dose of 1.5 to 2.0 mug, for periods up to 1 year. They showed increased calcium absorption, positive calcium and phosphorus balances, moderate increases in serum calcium levels, marked reductions in serum alkaline phosphatase levels, a decrease in serum immunoreactive parathyroid hormone levels, and radiologic and histologic improvement in bone disease. One patient with proximal myopathy showed improvement in muscular strength. 1-Alphahydroxycholecalciferol appears to be effective therapy for renal osteodystrophy."} {"id": "PMID:1259264", "title": "Possible hepatotoxicity of Doxidan.", "content": "A patient with chronic constipation developed liver injury and leukopenia following the ingestion of Doxidan, a combination drug consisting of danthron and dioctyl calcium sulfosuccinate. Evidence is presented that dioctyl calcium sulfosuccinate may have potentiated the toxicity. The liver injury was associated with deposition of IgE in the Kupffer cells. The mechanism of toxicity remains unclear.", "contents": "Possible hepatotoxicity of Doxidan. A patient with chronic constipation developed liver injury and leukopenia following the ingestion of Doxidan, a combination drug consisting of danthron and dioctyl calcium sulfosuccinate. Evidence is presented that dioctyl calcium sulfosuccinate may have potentiated the toxicity. The liver injury was associated with deposition of IgE in the Kupffer cells. The mechanism of toxicity remains unclear."} {"id": "PMID:1259268", "title": "Bone scintiscanning updated.", "content": "Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained.", "contents": "Bone scintiscanning updated. Use of modern materials and methods has given bone scintiscanning a larger role in clinical medicine, The safety and ready availability of newer agents have led to its greater use in investigating both benign and malignant disease of bone and joint. Present evidence suggests that abnormal accumulation of 99mTc-polyphosphate and its analogues results from ionic deposition at crystal surfaces in immature bone, this process being facilitated by an increase in bone vascularity. There is, also, a component of matrix localization. These factors are in keeping with the concept that abnormal scintiscan sites represent areas of increased osteoblastic activity, although this may be an oversimplification. Increasing evidence shows that the bone scintiscan is more sensitive than conventional radiography in detecting focal disease of bone, and its ability to reflect the immediate status of bone further complements radiographic findings. The main limitation of this method relates to nonspecificity of the results obtained."} {"id": "PMID:1259282", "title": "Ascorbic acid-induced uricosuria. A consequency of megavitamin therapy.", "content": "The effect of ascorbic acid on the serum and urinary uric acid was studied in 14 subjects. Two to 6 h after the ingestion of 4.0 g of ascorbic acid, the fractional clearance of uric acid increased to 202% +/- 41% of the control value. This uricosuria was inhibited by pyrazinamide and by low-dose acetylsalicylic acid, but was not accompanied by an increase of the creatinine clearnace. Ascorbic acid did not diminish protein-bound uric acid. In 3 subjects who ingested 8.0 g of ascorbic acid for 3 to 7 days the serum uric acid decreased by 1.2 to 3.1 mg/dl as a result of a sustained uricosuria. These results suggest that ascorbic acid could invalidate studies involving the measurement of uric acid and obscure the diagnosis of gout in some cases. Theoretically it could precipitate attacks of gouty arthritis or renal calculi in predisposed persons. These observations show a pharmacologic effect of megadoses of a simple vitamin.", "contents": "Ascorbic acid-induced uricosuria. A consequency of megavitamin therapy. The effect of ascorbic acid on the serum and urinary uric acid was studied in 14 subjects. Two to 6 h after the ingestion of 4.0 g of ascorbic acid, the fractional clearance of uric acid increased to 202% +/- 41% of the control value. This uricosuria was inhibited by pyrazinamide and by low-dose acetylsalicylic acid, but was not accompanied by an increase of the creatinine clearnace. Ascorbic acid did not diminish protein-bound uric acid. In 3 subjects who ingested 8.0 g of ascorbic acid for 3 to 7 days the serum uric acid decreased by 1.2 to 3.1 mg/dl as a result of a sustained uricosuria. These results suggest that ascorbic acid could invalidate studies involving the measurement of uric acid and obscure the diagnosis of gout in some cases. Theoretically it could precipitate attacks of gouty arthritis or renal calculi in predisposed persons. These observations show a pharmacologic effect of megadoses of a simple vitamin."} {"id": "PMID:1259283", "title": "Combination chemotherapy for advanced breast cancer: response and effect on survival.", "content": "Forty patients with metastatic breast cancer who had received no previous cytotoxic therapy were treated with a combination chemotherapy program CMF (P), which included methotrexate, 60 mg/m2, and 5-fluorouracil, 700 mg/m2 intravenously on the first and eighth days, in addition to cyclophosphamide, 100 mg/m2, and prednisone, 40 mg/m2, by mouth daily from the first to the fourteenth day of a 28-day cycle. Only 2 of 25 patients responded to hormonal therapy or endocrine ablation. Twenty-seven of the 40 patients (68%) had a complete response (8 patients) or partial response (19 patients). Lung, soft tissue, and nodal metastases were the most responsive sites. The median survival of 18 months for the responding group. The nonresponders had a median survival of 4 months. The toxicity was primarily hematologic and was especially severe in patients with functional liver impairment due to metastatic disease.", "contents": "Combination chemotherapy for advanced breast cancer: response and effect on survival. Forty patients with metastatic breast cancer who had received no previous cytotoxic therapy were treated with a combination chemotherapy program CMF (P), which included methotrexate, 60 mg/m2, and 5-fluorouracil, 700 mg/m2 intravenously on the first and eighth days, in addition to cyclophosphamide, 100 mg/m2, and prednisone, 40 mg/m2, by mouth daily from the first to the fourteenth day of a 28-day cycle. Only 2 of 25 patients responded to hormonal therapy or endocrine ablation. Twenty-seven of the 40 patients (68%) had a complete response (8 patients) or partial response (19 patients). Lung, soft tissue, and nodal metastases were the most responsive sites. The median survival of 18 months for the responding group. The nonresponders had a median survival of 4 months. The toxicity was primarily hematologic and was especially severe in patients with functional liver impairment due to metastatic disease."} {"id": "PMID:1259284", "title": "The clinical features of sclerosteosis. A review of the manifestations in twenty-five affected individuals.", "content": "Sclerosteosis is a unique autosomal recessive condition in which skeletal overgrowth is associated with syndactyly and digital malformation. Analysis of the course and clinical features in 25 affected individuals showed that the condition is progressive and potentially lethal. Facial palsy and deafness are common complications and raised intracranial pressure may develop. The clinical and radiographic stigmata of sclerosteosis permit differentiation from the other disorders of the \"osteopetrosis\" or \"Albers-Sch\u00f6nberg disease\" group, in which bony thickening and cranial nerve palsy occur.", "contents": "The clinical features of sclerosteosis. A review of the manifestations in twenty-five affected individuals. Sclerosteosis is a unique autosomal recessive condition in which skeletal overgrowth is associated with syndactyly and digital malformation. Analysis of the course and clinical features in 25 affected individuals showed that the condition is progressive and potentially lethal. Facial palsy and deafness are common complications and raised intracranial pressure may develop. The clinical and radiographic stigmata of sclerosteosis permit differentiation from the other disorders of the \"osteopetrosis\" or \"Albers-Sch\u00f6nberg disease\" group, in which bony thickening and cranial nerve palsy occur."} {"id": "PMID:1259285", "title": "Chronic respiratory disease in hemp workers. A follow-up study, 1967-1974.", "content": "Many soft-hemp workers with more than 20 years' exposure to dust have chronic respiratory symptoms and obstructive lung function loss. During 7 years of follow-up, these workers had significantly higher occurrences of chronic cough and phlegm and dyspnea than control subjects and a significantly larger annual decline of forced expiratory volume in 1 second (FEV1.0) than control subjects, with a particularly marked difference between 20- to 44-year-old nonsmoking controls and hemp workers. We believe that deterioration of lung function among hemp workers begins before the age of 45 and that it continues even if further exposure to dust ceases. Textile workers should be advised to avoid further exposure to dust at a time when their ventilatory lung function (in the absence of effects of acute exposure) is sufficient to prevent future development of disabling function loss.", "contents": "Chronic respiratory disease in hemp workers. A follow-up study, 1967-1974. Many soft-hemp workers with more than 20 years' exposure to dust have chronic respiratory symptoms and obstructive lung function loss. During 7 years of follow-up, these workers had significantly higher occurrences of chronic cough and phlegm and dyspnea than control subjects and a significantly larger annual decline of forced expiratory volume in 1 second (FEV1.0) than control subjects, with a particularly marked difference between 20- to 44-year-old nonsmoking controls and hemp workers. We believe that deterioration of lung function among hemp workers begins before the age of 45 and that it continues even if further exposure to dust ceases. Textile workers should be advised to avoid further exposure to dust at a time when their ventilatory lung function (in the absence of effects of acute exposure) is sufficient to prevent future development of disabling function loss."} {"id": "PMID:1259286", "title": "Interstital lung disease due to contamination of forced air systems.", "content": "Eight patients had hypersensitivity pneumonitis due to contaminated home or office forced-air heating or air-conditioning systems. We studied their clinical and laboratory features, and the results indicated that this disease may occur as an acute or insidious form differing in type and intensity of respiratory and systemic symptoms. Thermophilic actinomycetes contaminatinf the forced air systems were identified as the sensitizing agents in most cases. Precipitating antibodies to the organisms could be shown in the serums of the patients and the antigen identified by immunofluorescent studies in the three lung biopsies examined by this method. Inhalation challenge studies with the cultured organism or other materials obtained from the forced air systems reproduced the clinical syndrome in the four patients tested. Avoidance of the contaminated system, and the use of corticosteroids in more severe cases,seems to be appropriate therapy for patients with this disease.", "contents": "Interstital lung disease due to contamination of forced air systems. Eight patients had hypersensitivity pneumonitis due to contaminated home or office forced-air heating or air-conditioning systems. We studied their clinical and laboratory features, and the results indicated that this disease may occur as an acute or insidious form differing in type and intensity of respiratory and systemic symptoms. Thermophilic actinomycetes contaminatinf the forced air systems were identified as the sensitizing agents in most cases. Precipitating antibodies to the organisms could be shown in the serums of the patients and the antigen identified by immunofluorescent studies in the three lung biopsies examined by this method. Inhalation challenge studies with the cultured organism or other materials obtained from the forced air systems reproduced the clinical syndrome in the four patients tested. Avoidance of the contaminated system, and the use of corticosteroids in more severe cases,seems to be appropriate therapy for patients with this disease."} {"id": "PMID:1259287", "title": "Multiple myeloma in young persons.", "content": "Three young men were found to have multiple myeloma. Because their ages ranged from 17 to 22 years, the diagnosis was not considered initially, and then it was doubted until electrophoretic studies were completed. In none was the disease far advanced. These patients are the first well-documented group of young persons with multiple myeloma.", "contents": "Multiple myeloma in young persons. Three young men were found to have multiple myeloma. Because their ages ranged from 17 to 22 years, the diagnosis was not considered initially, and then it was doubted until electrophoretic studies were completed. In none was the disease far advanced. These patients are the first well-documented group of young persons with multiple myeloma."} {"id": "PMID:1259291", "title": "Marital sexual dysfunction:introductory concepts.", "content": "The concepts presented in this overview of marital sexual dysfunction are derived from increasing clinical experience with couples who seek help for their sexual problems. These couples, in marked contrast to couples with good sexual functioning, usually report a steady state of emotional dissatisfaction and minimal physical pleasure from sex. The affectual and behavioral consequences of persistent dysfunction are reviewed. Sexual therapy is discussed in terms of its two elements, sensate focus and psychotherapy. The various tastks which the sexual therapist may have to accomplish with individual couples are described. Consideration is given to the specific hypothese usually offered as explanation for sexual dysfunction-i.e., organic factors, varying degrees of relationship failure, poor communication, sexual ignorance, performance anxiety, and intrapsychic residua of past experience. A protocol for the screening physician to use in the formulation of a reasonable clinical plan for dysfunctional couples is included.", "contents": "Marital sexual dysfunction:introductory concepts. The concepts presented in this overview of marital sexual dysfunction are derived from increasing clinical experience with couples who seek help for their sexual problems. These couples, in marked contrast to couples with good sexual functioning, usually report a steady state of emotional dissatisfaction and minimal physical pleasure from sex. The affectual and behavioral consequences of persistent dysfunction are reviewed. Sexual therapy is discussed in terms of its two elements, sensate focus and psychotherapy. The various tastks which the sexual therapist may have to accomplish with individual couples are described. Consideration is given to the specific hypothese usually offered as explanation for sexual dysfunction-i.e., organic factors, varying degrees of relationship failure, poor communication, sexual ignorance, performance anxiety, and intrapsychic residua of past experience. A protocol for the screening physician to use in the formulation of a reasonable clinical plan for dysfunctional couples is included."} {"id": "PMID:1259292", "title": "Immunotherapy and human tumor immunology.", "content": "Present knowledge about the immune response to tumors in man is briefly reviewed, and the effects of cancer on immune-system functions are noted. The concepts that human tumors elicit cell-mediated immune responses to tumor antigens are re-examined and modified; for example, cell-mediated immunity may be detectable only at certain stages of tumor growth. Introduction of more sensitive methods for detecting antibodies is providing additional evidence for humoral immune responses to tumor-associated antigens. The present proliminary approaches to immunotherapy, particularly the use of adjuvants such as BCG and Corynebacterium parvum, are assessed, and initial pharmacoimmunologic findings with these agents are reported. The field of tumor immunology is in a dynamic state of development, with input from many areas of immunology and oncology. Carefully controlled clinical trials of these therapeutic regimens will be required to establish the value and indications for the use of such procedures.", "contents": "Immunotherapy and human tumor immunology. Present knowledge about the immune response to tumors in man is briefly reviewed, and the effects of cancer on immune-system functions are noted. The concepts that human tumors elicit cell-mediated immune responses to tumor antigens are re-examined and modified; for example, cell-mediated immunity may be detectable only at certain stages of tumor growth. Introduction of more sensitive methods for detecting antibodies is providing additional evidence for humoral immune responses to tumor-associated antigens. The present proliminary approaches to immunotherapy, particularly the use of adjuvants such as BCG and Corynebacterium parvum, are assessed, and initial pharmacoimmunologic findings with these agents are reported. The field of tumor immunology is in a dynamic state of development, with input from many areas of immunology and oncology. Carefully controlled clinical trials of these therapeutic regimens will be required to establish the value and indications for the use of such procedures."} {"id": "PMID:1259293", "title": "Geriatric care in the United Kingdom: an American perspective.", "content": "Geriatric care is a complex and challenging aspect of health care. The United Kingdom, with 13.6% of its population over 65 years of age, compared to 10.1% in the United States, has given special attention to this field. Characteristics of the British system include financing through the National Health Service, existence of a specialty of geriatrics, absence of \"nursing homes,\" emphasis on home care, and avoidance of \"heroics\" for the terminally ill. While British life expectancy at birth is longer than that for Americans, the opposite is now true for those over 65. The British have made efforts to maximize efficiency in a high-demand, comparatively low-resource context. But there are limits to which professional dedication and patient manipulation can be pushed. Some new policy directions-primarily aimed at prevention and other methods of reducing demand, other than reimposing financial barriers-may have to be explored.", "contents": "Geriatric care in the United Kingdom: an American perspective. Geriatric care is a complex and challenging aspect of health care. The United Kingdom, with 13.6% of its population over 65 years of age, compared to 10.1% in the United States, has given special attention to this field. Characteristics of the British system include financing through the National Health Service, existence of a specialty of geriatrics, absence of \"nursing homes,\" emphasis on home care, and avoidance of \"heroics\" for the terminally ill. While British life expectancy at birth is longer than that for Americans, the opposite is now true for those over 65. The British have made efforts to maximize efficiency in a high-demand, comparatively low-resource context. But there are limits to which professional dedication and patient manipulation can be pushed. Some new policy directions-primarily aimed at prevention and other methods of reducing demand, other than reimposing financial barriers-may have to be explored."} {"id": "PMID:1259294", "title": "An approach to teaching the introduction to clinical medicine.", "content": "An approach to teaching the introduction of clinical medicine to medical students is described. It is based on (A) gradual exposure to patients and step-by-step introduction to the objectives and techniques of history taking, with emphasis on training for symptom identification; (B) early exposure to the problem-oriented approach; (C) early diagnostic hypothesis generation; and (D) self-directed learning. The objectives of the proposed approach are to teach students to communicate with patients, to teach the skills of history taking and physical examination, and to introduce the problem-solving strategies that characterize the diagnostic reasoning of experienced physicians.", "contents": "An approach to teaching the introduction to clinical medicine. An approach to teaching the introduction of clinical medicine to medical students is described. It is based on (A) gradual exposure to patients and step-by-step introduction to the objectives and techniques of history taking, with emphasis on training for symptom identification; (B) early exposure to the problem-oriented approach; (C) early diagnostic hypothesis generation; and (D) self-directed learning. The objectives of the proposed approach are to teach students to communicate with patients, to teach the skills of history taking and physical examination, and to introduce the problem-solving strategies that characterize the diagnostic reasoning of experienced physicians."} {"id": "PMID:1259307", "title": "Medical usage and abusage: \"prevalence\" and \"incidence\".", "content": "In view of the frequent misuse of the term \"incidence,\" the concepts of incidence, prevalence, and period prevalence are defined and illustrated. The importance of restricting \"incidence\" to the rate of development of new events in a population or a group of patients, per unit of time, is stressed. Clearly distinguishing incidence from prevalence or simple proportion can help both in the understanding and the communication of findings in patient groups.", "contents": "Medical usage and abusage: \"prevalence\" and \"incidence\". In view of the frequent misuse of the term \"incidence,\" the concepts of incidence, prevalence, and period prevalence are defined and illustrated. The importance of restricting \"incidence\" to the rate of development of new events in a population or a group of patients, per unit of time, is stressed. Clearly distinguishing incidence from prevalence or simple proportion can help both in the understanding and the communication of findings in patient groups."} {"id": "PMID:1259308", "title": "Malignant degeneration of nonirradiated juvenile laryngeal papillomatosis.", "content": "Malignant degeneration in nonirradiated juvenile laryngeal papillomatosis is exceedingly rare. Review of the world literature reveals one case in the English literature and two in the German literature. A 23-year-old patient, representing the youngest reported case in English literature, is presented.", "contents": "Malignant degeneration of nonirradiated juvenile laryngeal papillomatosis. Malignant degeneration in nonirradiated juvenile laryngeal papillomatosis is exceedingly rare. Review of the world literature reveals one case in the English literature and two in the German literature. A 23-year-old patient, representing the youngest reported case in English literature, is presented."} {"id": "PMID:1259310", "title": "Caloric and optokinetic nystagmus in cerebellar patients.", "content": "In certain cerebellar lesions, optokinetic tracking is deficient, especially on tracking or following to the ipsilateral side. However, in many cases optokinetic nystagmus can occur, and apparently in better degree than would be expected from a study of pendulum tracking. This may be due to the patient leading into the stimulus and picking it up as soon as it is presented in far lateral gaze (in the direction of the fast component) and allowing the drift caused by the tone deficit to assist the tracking. An added vestibular tone can eliminate such a pseudo reflex. Induced vestibular nystagmus is enhanced and assumes a more dominant role so that optokinetic nystagmus is overcome, not only on gaze to the side of the tracking, but also on straight ahead gaze and even on some deviation of the eyes in the opposite direction.", "contents": "Caloric and optokinetic nystagmus in cerebellar patients. In certain cerebellar lesions, optokinetic tracking is deficient, especially on tracking or following to the ipsilateral side. However, in many cases optokinetic nystagmus can occur, and apparently in better degree than would be expected from a study of pendulum tracking. This may be due to the patient leading into the stimulus and picking it up as soon as it is presented in far lateral gaze (in the direction of the fast component) and allowing the drift caused by the tone deficit to assist the tracking. An added vestibular tone can eliminate such a pseudo reflex. Induced vestibular nystagmus is enhanced and assumes a more dominant role so that optokinetic nystagmus is overcome, not only on gaze to the side of the tracking, but also on straight ahead gaze and even on some deviation of the eyes in the opposite direction."} {"id": "PMID:1259309", "title": "Rupture of the round window membrane.", "content": "A case of sudden deafness due to rupture of the round window membrane is presented. Nineteen similar cases have previously been reported in the literature. In a review of these twenty patients, it is noted that a history of concurrent physical effort or barotrauma was present in eighteen. This supports the view that the injury is produced by pressure changes acting either along the cochlear aqueduct (the explosive route) or, directly on the middle ear structures (the implosive route). At operation, the rupture may be difficult to see, and a separate leak from the oval window may be present. The timing of any surgical intervention is important. The authors recommend that this should be deferred for one week after the onset of symptoms, as the fistula may heal spontaneously. If no definite improvement has occurred at the end of this time, then tympanotomy should be undertaken during the next week.", "contents": "Rupture of the round window membrane. A case of sudden deafness due to rupture of the round window membrane is presented. Nineteen similar cases have previously been reported in the literature. In a review of these twenty patients, it is noted that a history of concurrent physical effort or barotrauma was present in eighteen. This supports the view that the injury is produced by pressure changes acting either along the cochlear aqueduct (the explosive route) or, directly on the middle ear structures (the implosive route). At operation, the rupture may be difficult to see, and a separate leak from the oval window may be present. The timing of any surgical intervention is important. The authors recommend that this should be deferred for one week after the onset of symptoms, as the fistula may heal spontaneously. If no definite improvement has occurred at the end of this time, then tympanotomy should be undertaken during the next week."} {"id": "PMID:1259313", "title": "Technique for glottic reconstruction following vertical partial laryngectomy: a preliminary report.", "content": "In order to obtain a good phonatory function after glottic reconstruction following vertical partial laryngectomy, the following basic conditions should be satisfied: (1) adequate glottic closure should occur during phonation; (2) the top of the bulge constructed on the affected side should be located at the level of the vocal cord in order to facilitate vocal cord vibration and to prevent false cord vibration; and (3) the surface of the bulge should be smooth. A technique for glottic reconstruction which appears to meet these conditions is described. The sternohyoid muscle is dissected at the level 5 cm below the vocal cord, and the upper portion is used as a single pedicled flap. The muscle flap is bent approximately 90 degrees at the level of the upper border of the cricoid cartilage and inserted into the intralaryngeal wound so as to make a large bulge. The muscle flap is covered by hypopharyngeal mucosa or a free graft of oral mucosa.", "contents": "Technique for glottic reconstruction following vertical partial laryngectomy: a preliminary report. In order to obtain a good phonatory function after glottic reconstruction following vertical partial laryngectomy, the following basic conditions should be satisfied: (1) adequate glottic closure should occur during phonation; (2) the top of the bulge constructed on the affected side should be located at the level of the vocal cord in order to facilitate vocal cord vibration and to prevent false cord vibration; and (3) the surface of the bulge should be smooth. A technique for glottic reconstruction which appears to meet these conditions is described. The sternohyoid muscle is dissected at the level 5 cm below the vocal cord, and the upper portion is used as a single pedicled flap. The muscle flap is bent approximately 90 degrees at the level of the upper border of the cricoid cartilage and inserted into the intralaryngeal wound so as to make a large bulge. The muscle flap is covered by hypopharyngeal mucosa or a free graft of oral mucosa."} {"id": "PMID:1259314", "title": "Brain stem and other responses in electric response audiometry.", "content": "For electric response audiometry of young children who require sedation, an indicator is desired that is more reliable than the slow vertex potential. There are four leading candidates: 1) The electrocochleogram (ECochG) is very reliable with a transtympanic electrode on the promontory, but this is a surgical procedure and requires a general anesthetic. 2) The early midbrain responses give similar information with external electrodes, but they are complex and low in voltage. 3) The muscle reflexes (sonomotor responses) are a crude indicator with high and variable thresholds and are not suited to precise audiometry. 4) The \"middle\" responses, perhaps cortical in origin, are good candidates, but they have not yet been adequately validated in the clinic. For the midbrain responses and particularly for the ECochG, close synchronization of nerve impulses is essential. This requires a compromise with selectivity of frequency. High-tone audiometry by electrocochleography and midbrain responses is satisfactory, but limitations are increasingly severe below 2 kHz, where each sound wave is a separate acoustic stimulus. Low-frequency tones stimulate the basal turn of the cochlea at relatively low sensation levels. This makes assessment of the apical portion of the cochlea very difficult, even with the midbrain \"frequency-following response\" (FFR).", "contents": "Brain stem and other responses in electric response audiometry. For electric response audiometry of young children who require sedation, an indicator is desired that is more reliable than the slow vertex potential. There are four leading candidates: 1) The electrocochleogram (ECochG) is very reliable with a transtympanic electrode on the promontory, but this is a surgical procedure and requires a general anesthetic. 2) The early midbrain responses give similar information with external electrodes, but they are complex and low in voltage. 3) The muscle reflexes (sonomotor responses) are a crude indicator with high and variable thresholds and are not suited to precise audiometry. 4) The \"middle\" responses, perhaps cortical in origin, are good candidates, but they have not yet been adequately validated in the clinic. For the midbrain responses and particularly for the ECochG, close synchronization of nerve impulses is essential. This requires a compromise with selectivity of frequency. High-tone audiometry by electrocochleography and midbrain responses is satisfactory, but limitations are increasingly severe below 2 kHz, where each sound wave is a separate acoustic stimulus. Low-frequency tones stimulate the basal turn of the cochlea at relatively low sensation levels. This makes assessment of the apical portion of the cochlea very difficult, even with the midbrain \"frequency-following response\" (FFR)."} {"id": "PMID:1259315", "title": "Air humidity and mucociliary activity.", "content": "The relationship between varying humidity levels in the surrounding air and the mucociliary activity in rabbit trachea has been investigated. At a relative humidity (R.H.) above 70% the risk for ciliestasis is very small in the temperature range between 34 C and 40 C. At 37 C ciliestasis is not obtained until a relative humidity (R.H.) of 50% has been reached. The critical border is reached already at 60% R.H. if the temperature is 40 C. At 37 C and a decrement from 90% to 60% R.H. the mucociliary wave frequency was reduced by 30%, but at 40 C the corresponding reduction was 60%.", "contents": "Air humidity and mucociliary activity. The relationship between varying humidity levels in the surrounding air and the mucociliary activity in rabbit trachea has been investigated. At a relative humidity (R.H.) above 70% the risk for ciliestasis is very small in the temperature range between 34 C and 40 C. At 37 C ciliestasis is not obtained until a relative humidity (R.H.) of 50% has been reached. The critical border is reached already at 60% R.H. if the temperature is 40 C. At 37 C and a decrement from 90% to 60% R.H. the mucociliary wave frequency was reduced by 30%, but at 40 C the corresponding reduction was 60%."} {"id": "PMID:1259316", "title": "The peripheral hearing mechanism: a biochemical and biological approach.", "content": "A new approach is described to the problem or hearing at energy levels near threshold. Models depending on the macro-physics of levers are rejected. Instead, evidence is presented for frequency analysis, signal placement and energy transduction by the properties (known or experimentally determined) or the cochlea and of the structures within the scala media. The hypothesis developed rests on the established theorems of Gabor and Brillouin, and at the same time is based on the data of enzymology. Care is taken not only that the hypothesis does not conflict but that it is actually consonant with recent solid state physics. The cochlea by virtue of its internal geometry and contained column of fluid is considered to perform a Fourier analysis to a first approximation. This crude \"placement\" of the acoustic signal is refined by the semi-solid-state lattice of the tectorial membrane which far from permitting dissipation of the signal energy actually \"concentrates\" the energy at the membrane surface of the hair processes of a hair cell. Here biochemical transduction, akin to the processes known for other sensory cells, transforms acoustic energy through an ion-shuttling mechanism to the form of energy characteristic of living cells, viz. enzyme conformational changes.", "contents": "The peripheral hearing mechanism: a biochemical and biological approach. A new approach is described to the problem or hearing at energy levels near threshold. Models depending on the macro-physics of levers are rejected. Instead, evidence is presented for frequency analysis, signal placement and energy transduction by the properties (known or experimentally determined) or the cochlea and of the structures within the scala media. The hypothesis developed rests on the established theorems of Gabor and Brillouin, and at the same time is based on the data of enzymology. Care is taken not only that the hypothesis does not conflict but that it is actually consonant with recent solid state physics. The cochlea by virtue of its internal geometry and contained column of fluid is considered to perform a Fourier analysis to a first approximation. This crude \"placement\" of the acoustic signal is refined by the semi-solid-state lattice of the tectorial membrane which far from permitting dissipation of the signal energy actually \"concentrates\" the energy at the membrane surface of the hair processes of a hair cell. Here biochemical transduction, akin to the processes known for other sensory cells, transforms acoustic energy through an ion-shuttling mechanism to the form of energy characteristic of living cells, viz. enzyme conformational changes."} {"id": "PMID:1259317", "title": "Clinical manifestation of leprous rhinitis.", "content": "Over 25 million people in the World have leprosy. In the lepromatous form of the illness the nose is involved at a very early stage and in this paper the clinical manifestations are described. The nasal discharge in early untreated lepromatous leprosy contains vast numbers of the causative bacillus (M. leprae) and the important implications of these observations are discussed.", "contents": "Clinical manifestation of leprous rhinitis. Over 25 million people in the World have leprosy. In the lepromatous form of the illness the nose is involved at a very early stage and in this paper the clinical manifestations are described. The nasal discharge in early untreated lepromatous leprosy contains vast numbers of the causative bacillus (M. leprae) and the important implications of these observations are discussed."} {"id": "PMID:1259318", "title": "Vidian nerve and the eustachian tube.", "content": "The vidian nerve was stimulated electrically in the dog and this resulted in a reduced patency of the Eustachian tube. The effect was atropine resistant. This physiological evidence in the dog corresponds to anatomical evidence in man of a parasympathetic, vasodilator nerve bundle passing through the vidian to the sphenopalatine ganglion and then via the pharyngeal nerve to the Eustachian tube mucosa. Additional parasympathetic routes to the tube may exist.", "contents": "Vidian nerve and the eustachian tube. The vidian nerve was stimulated electrically in the dog and this resulted in a reduced patency of the Eustachian tube. The effect was atropine resistant. This physiological evidence in the dog corresponds to anatomical evidence in man of a parasympathetic, vasodilator nerve bundle passing through the vidian to the sphenopalatine ganglion and then via the pharyngeal nerve to the Eustachian tube mucosa. Additional parasympathetic routes to the tube may exist."} {"id": "PMID:1259324", "title": "Slipping of the capital femoral epiphysis.", "content": "Experimental and clinical studies have shown that the capital femoral epiphysis slips by rotating backwards and downwards around the curved surface of the metaphysis and remains in a plane that lies posteriorly at right angles to the anteversion plane of the neck of the femur. The relevance of these findings to the diagnosis and treatment of the condition is discussed. A geometric flexion osteotomy designed to correct the deformity is described.", "contents": "Slipping of the capital femoral epiphysis. Experimental and clinical studies have shown that the capital femoral epiphysis slips by rotating backwards and downwards around the curved surface of the metaphysis and remains in a plane that lies posteriorly at right angles to the anteversion plane of the neck of the femur. The relevance of these findings to the diagnosis and treatment of the condition is discussed. A geometric flexion osteotomy designed to correct the deformity is described."} {"id": "PMID:1259325", "title": "Total knee replacement using the stabilized gliding prosthesis.", "content": "The stabilized gliding knee prosthesis has been designed as a compromise between the restrained hinged joints and the unconnected surface prostheses. It is a two-piece implant, allowing normal gliding movements of flexion and extension, and is stabilized by a rod between the femoral and tibial components which allows some lateral mobility and rotation while acting in place of the cruciate ligaments and in place of or in addition to the collateral ligaments. The indications for and the techniwue of implantation are described and the results of the first 53 operations are reported. Follow-up time is between 1 year and 2 1/2 years. The results of these operations using the stabilized gliding prosthesis are at least equal to those using hinged or condylar prostheses. So far there has been no case of loosening of either component, and the implant can be used successfully in patients in whom condylar prostheses fail owing to their lac of inbuilt stability.", "contents": "Total knee replacement using the stabilized gliding prosthesis. The stabilized gliding knee prosthesis has been designed as a compromise between the restrained hinged joints and the unconnected surface prostheses. It is a two-piece implant, allowing normal gliding movements of flexion and extension, and is stabilized by a rod between the femoral and tibial components which allows some lateral mobility and rotation while acting in place of the cruciate ligaments and in place of or in addition to the collateral ligaments. The indications for and the techniwue of implantation are described and the results of the first 53 operations are reported. Follow-up time is between 1 year and 2 1/2 years. The results of these operations using the stabilized gliding prosthesis are at least equal to those using hinged or condylar prostheses. So far there has been no case of loosening of either component, and the implant can be used successfully in patients in whom condylar prostheses fail owing to their lac of inbuilt stability."} {"id": "PMID:1259319", "title": "Parathyroid tumors as lateral pharyngeal masses: report of a case.", "content": "This is the first reported case in the literature describing a patient free of the systemic biochemical effects of hyperparathyroidism who presented with a lateral pharyngeal mass. Diagnosis of parathyroid adenoma was made by means of a transoral biopsy prior to definitive surgical treatment. The role of parathyroid lesions in lateral cervical masses is discussed.", "contents": "Parathyroid tumors as lateral pharyngeal masses: report of a case. This is the first reported case in the literature describing a patient free of the systemic biochemical effects of hyperparathyroidism who presented with a lateral pharyngeal mass. Diagnosis of parathyroid adenoma was made by means of a transoral biopsy prior to definitive surgical treatment. The role of parathyroid lesions in lateral cervical masses is discussed."} {"id": "PMID:1259326", "title": "Neurology of the temporomandibular joints: an experimental study.", "content": "Experiments on anaesthetized cats are described in which the reflex effects of stimulation of the mechanoreceptors in the temporomandibular joints on the ipsilateral and contralateral mandibular muscles were studied. The effects on this reflex activity and on dynamic manidublar muscle activity of the production of temporary and permanent dysfunction of the mechanoreceptors in different regions of the joint capsule were also studied. The significance of the findings in relation to the maintenance of normal jaw posture and the disturbance of mandibular muscular function by trauma, disease, and malocclusion is discussed.", "contents": "Neurology of the temporomandibular joints: an experimental study. Experiments on anaesthetized cats are described in which the reflex effects of stimulation of the mechanoreceptors in the temporomandibular joints on the ipsilateral and contralateral mandibular muscles were studied. The effects on this reflex activity and on dynamic manidublar muscle activity of the production of temporary and permanent dysfunction of the mechanoreceptors in different regions of the joint capsule were also studied. The significance of the findings in relation to the maintenance of normal jaw posture and the disturbance of mandibular muscular function by trauma, disease, and malocclusion is discussed."} {"id": "PMID:1259327", "title": "Presentation and management of aneurysms.", "content": "The aetiology and pathology of aneurysms, their sites of occurrence, and their general management are outlined. Since the abdominal aortic aneurysm is the type most commonly encountered by the surgeon its presentation, assessment, and operative and postoperative management are discussed in detail.", "contents": "Presentation and management of aneurysms. The aetiology and pathology of aneurysms, their sites of occurrence, and their general management are outlined. Since the abdominal aortic aneurysm is the type most commonly encountered by the surgeon its presentation, assessment, and operative and postoperative management are discussed in detail."} {"id": "PMID:1259320", "title": "Sudden deafnfess of vascular origin: a human temporal bone study.", "content": "Temporal bone changes are described in a 57-year-old man who had sudden onset of dizziness and unilateral deafness two months before death. The patient suffered from hypertension, and congestive and renal failure. At autopsy, subarachnoid hemorrhage with punctate cortical hemorrhages and arteriolar thickening involved the right superior cerebellar hemisphere. The pathological changes involved primarily the right cochlea, saccule and posterior ampulla, and were consistent with vascular embarrassment of the temporal bone of two months duration. The cochlea demonstrated total loss of the organ of Corti and severe degenerative changes of the stria vascularis, spiral ligament, outer sulcus cells and distal cochlear nerve fibers. The saccule demonstrated loss of its macula and nerve fibers. The posterior ampulla showed evidence of previous rupture of its membranous wall with fibrosis and beginning bone formation. Fresh hemorrhage, present in some areas of both temporal bones, was related to the patient's terminal subarachnoid hemorrhage.", "contents": "Sudden deafnfess of vascular origin: a human temporal bone study. Temporal bone changes are described in a 57-year-old man who had sudden onset of dizziness and unilateral deafness two months before death. The patient suffered from hypertension, and congestive and renal failure. At autopsy, subarachnoid hemorrhage with punctate cortical hemorrhages and arteriolar thickening involved the right superior cerebellar hemisphere. The pathological changes involved primarily the right cochlea, saccule and posterior ampulla, and were consistent with vascular embarrassment of the temporal bone of two months duration. The cochlea demonstrated total loss of the organ of Corti and severe degenerative changes of the stria vascularis, spiral ligament, outer sulcus cells and distal cochlear nerve fibers. The saccule demonstrated loss of its macula and nerve fibers. The posterior ampulla showed evidence of previous rupture of its membranous wall with fibrosis and beginning bone formation. Fresh hemorrhage, present in some areas of both temporal bones, was related to the patient's terminal subarachnoid hemorrhage."} {"id": "PMID:1259385", "title": "Effect of temperature on the rate of the transparent to opaque colony type transition in Mycobacterium avium.", "content": "The results of drug susceptibility tests were found to be affected by changes that occur spontaneously in populations of Mycobacterium avium maintained in the laboratory. Because the transparent colony type variant was resistant to antituberculosis chemotherapeutic agents and the opaque colony type variant was usually susceptible to these agents, the transition of transparent to opaque colony type was investigated. The rate of the transition was found to be temperature dependent and, in agreement with a previous report, was found to be about 10(-4) to 10(-5) per generation at 37 C. Reversion was found to occur at a rate of 10(-6) to 10(-7) at 37 C. The mutation rate from susceptibility to resistance to rifampin, kanamycin, and erythromycin was about 10(-8) to 10(-9) mutations per bacterium per generation. Judged from our data, the high rate of the transparent to opaque variation was not caused either by mutator effects or by the occurrence of extrachromosomal genes in these bacteria, but could have been due to selective mechanisms still incompletely understood.", "contents": "Effect of temperature on the rate of the transparent to opaque colony type transition in Mycobacterium avium. The results of drug susceptibility tests were found to be affected by changes that occur spontaneously in populations of Mycobacterium avium maintained in the laboratory. Because the transparent colony type variant was resistant to antituberculosis chemotherapeutic agents and the opaque colony type variant was usually susceptible to these agents, the transition of transparent to opaque colony type was investigated. The rate of the transition was found to be temperature dependent and, in agreement with a previous report, was found to be about 10(-4) to 10(-5) per generation at 37 C. Reversion was found to occur at a rate of 10(-6) to 10(-7) at 37 C. The mutation rate from susceptibility to resistance to rifampin, kanamycin, and erythromycin was about 10(-8) to 10(-9) mutations per bacterium per generation. Judged from our data, the high rate of the transparent to opaque variation was not caused either by mutator effects or by the occurrence of extrachromosomal genes in these bacteria, but could have been due to selective mechanisms still incompletely understood."} {"id": "PMID:1259386", "title": "Induction of erythromycin resistance in Staphyloccus aureus by erythromycin derivatives.", "content": "The ability of 53 erythromycin analogues to induce resistance to erythromycin in Staphlococcus aureus was evaluated. Only derivatives with antibacterial activity induced resistance, although some antibacterial compounds did not induce resistance. No derivatives without antibacterial activity but with ability to induce resistance were found.", "contents": "Induction of erythromycin resistance in Staphyloccus aureus by erythromycin derivatives. The ability of 53 erythromycin analogues to induce resistance to erythromycin in Staphlococcus aureus was evaluated. Only derivatives with antibacterial activity induced resistance, although some antibacterial compounds did not induce resistance. No derivatives without antibacterial activity but with ability to induce resistance were found."} {"id": "PMID:1259387", "title": "Pharmacological studies with cefamandole in human volunteers.", "content": "Serum and urine concentrations were measured after administration of 0.5-and 1-g doses of cefamandole intramuscularly and intravenously to healthy volunteers. Intramuscular doses of 0.5 and 1 g yielded serum concentrations at 1 h of 14.7 and 35.6 mug/ml, respectively. Significant antibacterial concentrations persisted through h 8. Intravenous doses of 0.5 and 1 g resulted in respective peak serum levels of 21 mug/ml at 45 min and 103 mug/ml at 15 min; these serum levels rapidly declined. Very high urine concentrations were achieved during the first 8 h after injection.", "contents": "Pharmacological studies with cefamandole in human volunteers. Serum and urine concentrations were measured after administration of 0.5-and 1-g doses of cefamandole intramuscularly and intravenously to healthy volunteers. Intramuscular doses of 0.5 and 1 g yielded serum concentrations at 1 h of 14.7 and 35.6 mug/ml, respectively. Significant antibacterial concentrations persisted through h 8. Intravenous doses of 0.5 and 1 g resulted in respective peak serum levels of 21 mug/ml at 45 min and 103 mug/ml at 15 min; these serum levels rapidly declined. Very high urine concentrations were achieved during the first 8 h after injection."} {"id": "PMID:1259388", "title": "Interspecies transformation of streptomycin resistance in oral streptococci.", "content": "Donor deoxyribonucleic acid extracted from streptomycin-resistant (Str(R)) mutant derivatives of a variety of strains of Streptococcus mutans, S. salivarius, and S. sanguis was used to transform streptomycin resistance into competent S. sanguis strain Challis. Transfer of genetic markers for sorbitol and mannitol fermentation and for extracellular polysaccharide as demonstrated by colonial morphology was not detected in this study. Reciprocal transformation between strain Challis and other oral streptococci could not be demonstrated. Transformation frequencies for Str(R) were relatively efficient among S. sanguis strains, with lower but significant frequencies demonstrated with strain Challis and donor deoxyribonucleic acid derived from other oral streptococci.", "contents": "Interspecies transformation of streptomycin resistance in oral streptococci. Donor deoxyribonucleic acid extracted from streptomycin-resistant (Str(R)) mutant derivatives of a variety of strains of Streptococcus mutans, S. salivarius, and S. sanguis was used to transform streptomycin resistance into competent S. sanguis strain Challis. Transfer of genetic markers for sorbitol and mannitol fermentation and for extracellular polysaccharide as demonstrated by colonial morphology was not detected in this study. Reciprocal transformation between strain Challis and other oral streptococci could not be demonstrated. Transformation frequencies for Str(R) were relatively efficient among S. sanguis strains, with lower but significant frequencies demonstrated with strain Challis and donor deoxyribonucleic acid derived from other oral streptococci."} {"id": "PMID:1259389", "title": "Micromonospora-produced gentamicin components.", "content": "After the chromatographic separation of [methyl-(14)C]gentamicin major (C) components from a large-scale radioactive fermentation (Lee et al., 1974), [methyl-(14)C]gentamicin minor (polar) components (A, B, B(1), X(2), and G-418) were isolated from subsequent chromatography of the remaining antibiotic mixture. When l-[methyl-(14)C]methionine was added at the onset of biosynthesis of the gentamicin components, incorporation of label into the minor components preceded incorporation into the major components. Degradation occurred when [methyl-(14)C]gentamicin major components (C(1), C(2) and C(1)a) were added respectively to the gentamicin-producing culture medium and shaken.", "contents": "Micromonospora-produced gentamicin components. After the chromatographic separation of [methyl-(14)C]gentamicin major (C) components from a large-scale radioactive fermentation (Lee et al., 1974), [methyl-(14)C]gentamicin minor (polar) components (A, B, B(1), X(2), and G-418) were isolated from subsequent chromatography of the remaining antibiotic mixture. When l-[methyl-(14)C]methionine was added at the onset of biosynthesis of the gentamicin components, incorporation of label into the minor components preceded incorporation into the major components. Degradation occurred when [methyl-(14)C]gentamicin major components (C(1), C(2) and C(1)a) were added respectively to the gentamicin-producing culture medium and shaken."} {"id": "PMID:1259390", "title": "Bone concentrations of antimicrobial agents after parenteral administration.", "content": "Bone concentrations of seven antimicrobial agents were determined after parenteral administration. Antibiotics were administered in large doses at customary intervals for 12 to 20 h before total hip or knee replacement; anticipated levels of each drug were achieved in the serum. Methicillin, carbenicillin, and clindamycin were detected in bone with greatest frequency. Cefazolin and gentamicin were each detected in bone specimens from only one of four patients. Neither penicillin G nor cephalothin was present in bone in sufficient quantity to be measurable. These data suggest that a number of factors, in addition to serum concentration, affect concentration of antimicrobial agents in bone. The clinical significance of the relationship between bone concentrations of antibiotics and therapeutic outcome is not certain.", "contents": "Bone concentrations of antimicrobial agents after parenteral administration. Bone concentrations of seven antimicrobial agents were determined after parenteral administration. Antibiotics were administered in large doses at customary intervals for 12 to 20 h before total hip or knee replacement; anticipated levels of each drug were achieved in the serum. Methicillin, carbenicillin, and clindamycin were detected in bone with greatest frequency. Cefazolin and gentamicin were each detected in bone specimens from only one of four patients. Neither penicillin G nor cephalothin was present in bone in sufficient quantity to be measurable. These data suggest that a number of factors, in addition to serum concentration, affect concentration of antimicrobial agents in bone. The clinical significance of the relationship between bone concentrations of antibiotics and therapeutic outcome is not certain."} {"id": "PMID:1259391", "title": "Protective effect of cephalothin against gentamincin-induced nephrotoxicity in rats.", "content": "The possibility that the nephrotoxicity of gentamicin may be potentiated by the concomitant administration of cephalothin was examined in a rat model. Cephalothin given once daily in dosages up to 800 mg/kg per day for 10 days produced no renal damage. Gentamicin, at 6 to 50 mg/kg per day, caused pathological changes which were dosage related and affected primarily the proximal tubular cells. Administration of the two drugs simultaneously resulted in a significant protective effect of cephalothin against gentamicin-related nephrotoxicity (P < 0.01). When the daily injections of the two agents were separated by an interval of 6 h, the protective effect was lost, and the resultant damage was the same as that due to gentamicin alone. The protective effect of cephalothin was reproduced by the administration of equiosmolar amounts of sulfate (sodium sulfate), suggesting that the phenomenon might be related to the presence of nonresorbable anion in the urine. These studies indicate that, in the rat, cephalothin does not potentiate, but, in fact, may prevent the nephrotoxic effects of gentamicin.", "contents": "Protective effect of cephalothin against gentamincin-induced nephrotoxicity in rats. The possibility that the nephrotoxicity of gentamicin may be potentiated by the concomitant administration of cephalothin was examined in a rat model. Cephalothin given once daily in dosages up to 800 mg/kg per day for 10 days produced no renal damage. Gentamicin, at 6 to 50 mg/kg per day, caused pathological changes which were dosage related and affected primarily the proximal tubular cells. Administration of the two drugs simultaneously resulted in a significant protective effect of cephalothin against gentamicin-related nephrotoxicity (P < 0.01). When the daily injections of the two agents were separated by an interval of 6 h, the protective effect was lost, and the resultant damage was the same as that due to gentamicin alone. The protective effect of cephalothin was reproduced by the administration of equiosmolar amounts of sulfate (sodium sulfate), suggesting that the phenomenon might be related to the presence of nonresorbable anion in the urine. These studies indicate that, in the rat, cephalothin does not potentiate, but, in fact, may prevent the nephrotoxic effects of gentamicin."} {"id": "PMID:1259392", "title": "Drug resistance and distribution of R factors in Salmonella strains.", "content": "Drug resistance and the distribution of R factors in Salmonella strains were surveyed using 1,980 strains isolated in Japan from 1955 to 1973. Resistances were mostly restricted to sulfanilamide (SA), tetracycline (TC), and streptomycin (SM), and combinations thereof. The demonstrated frequency of strains resistant to chloramphenicol (CM) was very low as compared with that in Escherichia coli and Shigella strains. In relation to resistance to TC, CM, SM and SA, the frequency of isolation of single resistance was the highest, followed by triple, double, and quadruple resistance in that order. Low frequency of isolation of quadruple resistance was due to the low frequency of CM resistance in Salmonella strains and differed from the E. coli or Shigella group. R factors with single TC resistance was most common, followed by those with TC,SM,SA; SM,SA; TC,CM,SM,SA; and single (SM and SA) resistance, in that order. Kanamycin and ampicillin resistance was unusual and mostly transmissible.", "contents": "Drug resistance and distribution of R factors in Salmonella strains. Drug resistance and the distribution of R factors in Salmonella strains were surveyed using 1,980 strains isolated in Japan from 1955 to 1973. Resistances were mostly restricted to sulfanilamide (SA), tetracycline (TC), and streptomycin (SM), and combinations thereof. The demonstrated frequency of strains resistant to chloramphenicol (CM) was very low as compared with that in Escherichia coli and Shigella strains. In relation to resistance to TC, CM, SM and SA, the frequency of isolation of single resistance was the highest, followed by triple, double, and quadruple resistance in that order. Low frequency of isolation of quadruple resistance was due to the low frequency of CM resistance in Salmonella strains and differed from the E. coli or Shigella group. R factors with single TC resistance was most common, followed by those with TC,SM,SA; SM,SA; TC,CM,SM,SA; and single (SM and SA) resistance, in that order. Kanamycin and ampicillin resistance was unusual and mostly transmissible."} {"id": "PMID:1259393", "title": "Clinical pharmacology of cefamandole as compared with cephalothin.", "content": "We compared the pharmacology of cefamandole and cephalothin in six healthy adult male volunteers. After a 1-g, 20-min intravenous (i.v.) infusion, the average peak blood level of cefamandole was 87.6 versus 64.1 mug/ml for cephalothin. An i.v. infusion of 500 mg/h for 2 h (after a loading dose of 750 mg) gave an average steady-state blood level of 28.5 mug/ml for cefamandole and 18.2 mug/ml for cephalothin. Mean peak serum levels after 1 g intramuscularly were similar for the two antibiotics (about 21 mug/ml), but with cefamandole they persisted longer, and the area under the blood level curve was about 25% greater. The average t((1/2)) as determined from both i.v. studies was 34 min for cefamandole versus 30 min for cephalothin. The mean serum clearance for cephalothin, due to its partial conversion to a metabolite, was much greater than for cefamandole (425 versus 272 ml/min per 1.73 m(2)), but the renal clearances were similar for the two antibiotics (268 versus 257 ml/min per 1.73 m(2)). Other values for cefamandole and cephalothin were: 24-h urinary excretion, 80 and 66%; serum protein binding, 74 and 70%; and apparent volume of distribution, 12.8 and 18.5 liters/1.73 m(2), respectively. Thus, the pharmacology of the two antibiotics was similar. Blood levels were somewhat higher with cefamandole i.v., but the results suggest that dosage regimens should be the same for the two antibiotics.", "contents": "Clinical pharmacology of cefamandole as compared with cephalothin. We compared the pharmacology of cefamandole and cephalothin in six healthy adult male volunteers. After a 1-g, 20-min intravenous (i.v.) infusion, the average peak blood level of cefamandole was 87.6 versus 64.1 mug/ml for cephalothin. An i.v. infusion of 500 mg/h for 2 h (after a loading dose of 750 mg) gave an average steady-state blood level of 28.5 mug/ml for cefamandole and 18.2 mug/ml for cephalothin. Mean peak serum levels after 1 g intramuscularly were similar for the two antibiotics (about 21 mug/ml), but with cefamandole they persisted longer, and the area under the blood level curve was about 25% greater. The average t((1/2)) as determined from both i.v. studies was 34 min for cefamandole versus 30 min for cephalothin. The mean serum clearance for cephalothin, due to its partial conversion to a metabolite, was much greater than for cefamandole (425 versus 272 ml/min per 1.73 m(2)), but the renal clearances were similar for the two antibiotics (268 versus 257 ml/min per 1.73 m(2)). Other values for cefamandole and cephalothin were: 24-h urinary excretion, 80 and 66%; serum protein binding, 74 and 70%; and apparent volume of distribution, 12.8 and 18.5 liters/1.73 m(2), respectively. Thus, the pharmacology of the two antibiotics was similar. Blood levels were somewhat higher with cefamandole i.v., but the results suggest that dosage regimens should be the same for the two antibiotics."} {"id": "PMID:1259394", "title": "Viridins, bacteriocins of alpha-hemolytic streptococci: isolation, characterization, and partial purification.", "content": "Bacteriocin-like activities were detected in 78% of 120 alpha-hemolytic streptococcal isolates. Inhibitory substances from three such isolates (one Streptococcus sanguis strain and two S. mitis strains) were investigated further and termed viridins (A, B, and C). The viridins were unique among bacteriocins of gram-positive bacteria in that they inhibited many gram-negative bacteria in addition to inhibition of a variety of gram-positive organisms. Viridins were obtained in a cell-free state only after mechanical disruption of bacteriocinogenic cells but could not be isolated from supernatant fluids of cultures of such bacteria or from freeze-thaw liquor of agar on which the bacteria had been grown. Viridin B could be partially purified by ammonium sulfate precipitation and by gel filtration on a Sephadex G-100 column. This bacteriocin had some unusual properties including heat lability, a narrow pH range of activity, and lack of adsorptive capacity to susceptible bacteria. Although viridin B was bactericidal to a Neisseria sicca strain, it was only bacteriostatic against a coagulase-negative staphylococcus.", "contents": "Viridins, bacteriocins of alpha-hemolytic streptococci: isolation, characterization, and partial purification. Bacteriocin-like activities were detected in 78% of 120 alpha-hemolytic streptococcal isolates. Inhibitory substances from three such isolates (one Streptococcus sanguis strain and two S. mitis strains) were investigated further and termed viridins (A, B, and C). The viridins were unique among bacteriocins of gram-positive bacteria in that they inhibited many gram-negative bacteria in addition to inhibition of a variety of gram-positive organisms. Viridins were obtained in a cell-free state only after mechanical disruption of bacteriocinogenic cells but could not be isolated from supernatant fluids of cultures of such bacteria or from freeze-thaw liquor of agar on which the bacteria had been grown. Viridin B could be partially purified by ammonium sulfate precipitation and by gel filtration on a Sephadex G-100 column. This bacteriocin had some unusual properties including heat lability, a narrow pH range of activity, and lack of adsorptive capacity to susceptible bacteria. Although viridin B was bactericidal to a Neisseria sicca strain, it was only bacteriostatic against a coagulase-negative staphylococcus."} {"id": "PMID:1259395", "title": "Influence of cephalosporin antibiotics on blood coagulation and platelet function.", "content": "Administration of cephalothin to normal volunteers in maximal doses of 300 mg/kg per day resulted in a combined defect of platelet function and blood coagulation. No such abnormalities were evident after infusion of cefazolin or cephapirin at a maximal dosage of 200 mg/kg per day. The observed thrombocytopathy was similar to but less severe than that induced by carbenicillin or ticarcillin and was not reflected by a prolonged bleeding time test or impaired prothrombin consumption. Moreover, it was not a consistent finding in those persons receiving cephalothin. A separate defect involving blood coagulation appeared to result from delayed fibrinogen-fibrin polymerization and was evidenced by extended values of the activated partial thromboplastin and thrombin time tests. It remains uncertain whether the abnormalities described may constitute clinically important hemostatic disorders in patients with normal renal function receiving large doses of cephalosporin antibiotics.", "contents": "Influence of cephalosporin antibiotics on blood coagulation and platelet function. Administration of cephalothin to normal volunteers in maximal doses of 300 mg/kg per day resulted in a combined defect of platelet function and blood coagulation. No such abnormalities were evident after infusion of cefazolin or cephapirin at a maximal dosage of 200 mg/kg per day. The observed thrombocytopathy was similar to but less severe than that induced by carbenicillin or ticarcillin and was not reflected by a prolonged bleeding time test or impaired prothrombin consumption. Moreover, it was not a consistent finding in those persons receiving cephalothin. A separate defect involving blood coagulation appeared to result from delayed fibrinogen-fibrin polymerization and was evidenced by extended values of the activated partial thromboplastin and thrombin time tests. It remains uncertain whether the abnormalities described may constitute clinically important hemostatic disorders in patients with normal renal function receiving large doses of cephalosporin antibiotics."} {"id": "PMID:1259396", "title": "Modification of bacterial respiration by a macromolecular polyanionic antibiotic produced by a marine Alteromonas.", "content": "A macromolecular polyanionic antibiotic produced by a marine bacterium belonging to the genus Alteromonas causes a large modification in bacterial respiration when added to the culture of several bacterial species in their early stage of growth. This antibiotic induces an increase of oxygen uptake and the production of hydrogen peroxide. The latter fact explains the high sensitivity of bacteria with low catalase activity and the antagonistic effect of pure catalase on antibiosis. The antibiotic could act at the level of the respiratory chain by setting up a flavinic respiration.", "contents": "Modification of bacterial respiration by a macromolecular polyanionic antibiotic produced by a marine Alteromonas. A macromolecular polyanionic antibiotic produced by a marine bacterium belonging to the genus Alteromonas causes a large modification in bacterial respiration when added to the culture of several bacterial species in their early stage of growth. This antibiotic induces an increase of oxygen uptake and the production of hydrogen peroxide. The latter fact explains the high sensitivity of bacteria with low catalase activity and the antagonistic effect of pure catalase on antibiosis. The antibiotic could act at the level of the respiratory chain by setting up a flavinic respiration."} {"id": "PMID:1259397", "title": "Beta-indoleethanol and beta-indolelactic acid production by Candida species: their antibacterial and autoantibiotic action.", "content": "Candida spp. grown in synthetic medium supplemented with l-tryptophan as sole nitrogen source produced beta-indoleethanol (beta-IEA) and beta-indolelactic acid (beta-ILA). These compounds isolated from the culture filtrates were characterized by ultraviolet, infrared, and nuclear magnetic resonance spectral studies. Using dl-[(3)H]trypotophan in the medium, labeled beta-IEA and beta-ILA were isolated. Further, beta-IEA was produced as a result incubating log-phase cells of C. albicans with beta-ILA. Both beta-IEA and beta-ILA inhibited the growth of gram-positive and -negative bacteria. Autoantibiotic action of these compounds on Candida spp. and the reversal of this inhibition were studied.", "contents": "Beta-indoleethanol and beta-indolelactic acid production by Candida species: their antibacterial and autoantibiotic action. Candida spp. grown in synthetic medium supplemented with l-tryptophan as sole nitrogen source produced beta-indoleethanol (beta-IEA) and beta-indolelactic acid (beta-ILA). These compounds isolated from the culture filtrates were characterized by ultraviolet, infrared, and nuclear magnetic resonance spectral studies. Using dl-[(3)H]trypotophan in the medium, labeled beta-IEA and beta-ILA were isolated. Further, beta-IEA was produced as a result incubating log-phase cells of C. albicans with beta-ILA. Both beta-IEA and beta-ILA inhibited the growth of gram-positive and -negative bacteria. Autoantibiotic action of these compounds on Candida spp. and the reversal of this inhibition were studied."} {"id": "PMID:1259398", "title": "Oxolinic acid in the treatment of typhoid fever due to chloramphenicol-resistant strains of Salmonella typhi.", "content": "Of 28 strains of Salmonella typhosa collected in late 1972 in Vietnam, 4 had minimum inhibitory concentrations to chloramphenicol of >100 mug/ml. Median minimum inhibitory concentrations of all strains to oxolinic acid were 0.39 mug/ml; ampicillin, 6.25 mug/ml; amoxicillin, 0.39 mug/ml. Widespread typhoid fever appeared in mid-1973 with more than three-fourths of strains found to be resistant to chloramphenicol. Peak serum concentrations of oxolinic acid average 3.0 mug/ml after the oral ingestion of 1.0 g. In July 1974, a pilot study was begun to evaluate the efficacy of oxolinic acid in vivo, recognizing the discrepancy between in vitro and in vivo results with many agents evaluated in the treatment of typhoid fever. Seven patients with typhoid fever, six with positive blood cultures, were treated with oxolinic acid (1.5 g twice daily by mouth, a daily dose that averaged 75 mg/kg per day) for 5 to 12 days. In four of six patients, blood cultures became negative at 2 to 3 days, with another being negative at 6 days. Despite negative blood cultures, all but one patient remained clinically ill with temperatures of >39.5 C at 4 to 9 days. All strains were susceptible to 0.19 mug of oxolinic acid per ml, and resistant strains did not occur. One patient died after being changed to ampicillin, one left against advice, three responded to amoxicillin, and one died with pseudomonas bacteremia. Toxicity to oxolinic acid did not occur.", "contents": "Oxolinic acid in the treatment of typhoid fever due to chloramphenicol-resistant strains of Salmonella typhi. Of 28 strains of Salmonella typhosa collected in late 1972 in Vietnam, 4 had minimum inhibitory concentrations to chloramphenicol of >100 mug/ml. Median minimum inhibitory concentrations of all strains to oxolinic acid were 0.39 mug/ml; ampicillin, 6.25 mug/ml; amoxicillin, 0.39 mug/ml. Widespread typhoid fever appeared in mid-1973 with more than three-fourths of strains found to be resistant to chloramphenicol. Peak serum concentrations of oxolinic acid average 3.0 mug/ml after the oral ingestion of 1.0 g. In July 1974, a pilot study was begun to evaluate the efficacy of oxolinic acid in vivo, recognizing the discrepancy between in vitro and in vivo results with many agents evaluated in the treatment of typhoid fever. Seven patients with typhoid fever, six with positive blood cultures, were treated with oxolinic acid (1.5 g twice daily by mouth, a daily dose that averaged 75 mg/kg per day) for 5 to 12 days. In four of six patients, blood cultures became negative at 2 to 3 days, with another being negative at 6 days. Despite negative blood cultures, all but one patient remained clinically ill with temperatures of >39.5 C at 4 to 9 days. All strains were susceptible to 0.19 mug of oxolinic acid per ml, and resistant strains did not occur. One patient died after being changed to ampicillin, one left against advice, three responded to amoxicillin, and one died with pseudomonas bacteremia. Toxicity to oxolinic acid did not occur."} {"id": "PMID:1259399", "title": "In vitro and clinical studies of cefatrizine, a new semisynthetic cephalosporin.", "content": "Cefatrizine, a new oral semisynthetic cephalosporin, was evaluated in vitro and in the treatment of 18 patients with acute urinary tract infection, pneumonia, and soft tissue infection. In vitro, it was more active than cephalexin for gram-positive and gram-negative bacteria. It was also more active than cephalothin, cefazolin, and cephapirin against most of the gram-negative bacteria but less active against the gram-positive bacteria. Of the patients treated with cefatrizine, only one failed to respond. This patient had pneumococcal conjunctivitis and hypogammaglobulinemia and neutropenia. The mean peak serum level after multiple 6-hourly doses of 500 mg was 6.2 mug/ml. The serum levels of cefatrizine necessary for inhibition of most susceptible organisms were well within the achievable range. The drug was well tolerated, and no renal, hepatic, or hematological toxicity was detected.", "contents": "In vitro and clinical studies of cefatrizine, a new semisynthetic cephalosporin. Cefatrizine, a new oral semisynthetic cephalosporin, was evaluated in vitro and in the treatment of 18 patients with acute urinary tract infection, pneumonia, and soft tissue infection. In vitro, it was more active than cephalexin for gram-positive and gram-negative bacteria. It was also more active than cephalothin, cefazolin, and cephapirin against most of the gram-negative bacteria but less active against the gram-positive bacteria. Of the patients treated with cefatrizine, only one failed to respond. This patient had pneumococcal conjunctivitis and hypogammaglobulinemia and neutropenia. The mean peak serum level after multiple 6-hourly doses of 500 mg was 6.2 mug/ml. The serum levels of cefatrizine necessary for inhibition of most susceptible organisms were well within the achievable range. The drug was well tolerated, and no renal, hepatic, or hematological toxicity was detected."} {"id": "PMID:1259400", "title": "Effect of amphotericin B and rifampin against Coccidioides immitis in vitro and in vivo.", "content": "Amphotericin B, the principal drug used for treating systemic mycoses, possesses undesirable toxic properties. The ability of this antibiotic to potentiate antifungal activity of other compounds suggests that lower doses of amphotericin B could be used in combination with a second drug without loss of therapeutic efficacy. In vitro tests demonstrated that amphotericin B potentiated rifampin against the mycelial growth phase of Coccidioides immitis but not against the spherule-endospore phase. Therapy for murine coccidioidomycosis with a combined amphotericin B-rifampin regimen was not better than treatment with amphotericin B alone; in fact, combined drugs may have been even less effective. This would have clinical significance for therapy of concurrent infections.", "contents": "Effect of amphotericin B and rifampin against Coccidioides immitis in vitro and in vivo. Amphotericin B, the principal drug used for treating systemic mycoses, possesses undesirable toxic properties. The ability of this antibiotic to potentiate antifungal activity of other compounds suggests that lower doses of amphotericin B could be used in combination with a second drug without loss of therapeutic efficacy. In vitro tests demonstrated that amphotericin B potentiated rifampin against the mycelial growth phase of Coccidioides immitis but not against the spherule-endospore phase. Therapy for murine coccidioidomycosis with a combined amphotericin B-rifampin regimen was not better than treatment with amphotericin B alone; in fact, combined drugs may have been even less effective. This would have clinical significance for therapy of concurrent infections."} {"id": "PMID:1259401", "title": "In vitro activity of BL-s640 against gram-negative bacilli and Staphylococcus aureus compared with activity of four other semisynthetic cephalosporins.", "content": "The in vitro activity of BL-S640 (cefatrizine) was determined against 674 recent clinical isolates of Staphylococcus aureus and Enterobacteriaceae. Activity against S. aureus was less than that of cephapirin, cephalothin, and cefazolin, but greater than that of cephalexin. Activity against gram-negative isolates was variable: BL-S640 was slightly less potent than cefazolin against Escherichia coli and Klebsiella, but more active than the other compounds. As for the more resistant gram-negative genera, BL-S640 was significantly superior to the control cephalosporins. The effect of inoculum size on the antibacterial activity was moderate for most organisms except Enterobacter, Providencia stuartii, and indole-positive Proteus, the median minimal inhibitory concentrations of which were 6 to 27 times lower when determined with a 10(-4)-diluted culture compared with the undiluted one. The stability in aqueous solution at 37 C was remarkably high at the lower pH values, but low at the neutral point.", "contents": "In vitro activity of BL-s640 against gram-negative bacilli and Staphylococcus aureus compared with activity of four other semisynthetic cephalosporins. The in vitro activity of BL-S640 (cefatrizine) was determined against 674 recent clinical isolates of Staphylococcus aureus and Enterobacteriaceae. Activity against S. aureus was less than that of cephapirin, cephalothin, and cefazolin, but greater than that of cephalexin. Activity against gram-negative isolates was variable: BL-S640 was slightly less potent than cefazolin against Escherichia coli and Klebsiella, but more active than the other compounds. As for the more resistant gram-negative genera, BL-S640 was significantly superior to the control cephalosporins. The effect of inoculum size on the antibacterial activity was moderate for most organisms except Enterobacter, Providencia stuartii, and indole-positive Proteus, the median minimal inhibitory concentrations of which were 6 to 27 times lower when determined with a 10(-4)-diluted culture compared with the undiluted one. The stability in aqueous solution at 37 C was remarkably high at the lower pH values, but low at the neutral point."} {"id": "PMID:1259402", "title": "In vitro activity, synergism, and testing parameters of amikacin, with comparisons to other aminoglycoside antibiotics.", "content": "The activity of the new aminoglycoside antibiotic, amikacin, was evaluated in vitro against 219 clinical bacterial isolates. One hundred eighty-nine of the 219 strains had agar dilution minimal inhibitory concentration values of 8.0 mug/ml or less for amikacin. Comparative agar dilution studies were performed for gentamicin, kanamycin, and tobramycin. Gentamicin was the most active overall, but tobramycin and amikacin also had significant activity against most bacterial groups. The effects of divalent cations on the susceptibility of Pseudomonas aeruginosa to amikacin were evaluated, and the minimal inhibitory concentration values varied sixfold over a range of divalent cation concentrations from 0.2 to 8.75 mg%. The effects of media and inoculum size on disk susceptibility testing with amikacin were also evaluated. In addition, a synergistic interaction between carbenicillin and amikacin against P. aeruginosa was demonstrated. Amikacin appears to be a promising new broad spectrum antimicrobial agent.", "contents": "In vitro activity, synergism, and testing parameters of amikacin, with comparisons to other aminoglycoside antibiotics. The activity of the new aminoglycoside antibiotic, amikacin, was evaluated in vitro against 219 clinical bacterial isolates. One hundred eighty-nine of the 219 strains had agar dilution minimal inhibitory concentration values of 8.0 mug/ml or less for amikacin. Comparative agar dilution studies were performed for gentamicin, kanamycin, and tobramycin. Gentamicin was the most active overall, but tobramycin and amikacin also had significant activity against most bacterial groups. The effects of divalent cations on the susceptibility of Pseudomonas aeruginosa to amikacin were evaluated, and the minimal inhibitory concentration values varied sixfold over a range of divalent cation concentrations from 0.2 to 8.75 mg%. The effects of media and inoculum size on disk susceptibility testing with amikacin were also evaluated. In addition, a synergistic interaction between carbenicillin and amikacin against P. aeruginosa was demonstrated. Amikacin appears to be a promising new broad spectrum antimicrobial agent."} {"id": "PMID:1259403", "title": "Antibiotic susceptibility of the subspecies of Bacteroides fragilis.", "content": "Strains (115) of Bacteroides fragilis were identified at the subspecific level and were tested for susceptibility to ampicillin, cephalothin, chloramphenicol, clindamycin, penicillin, and tetracycline using an agar dilution technique. We tested the following strains: B. fragilis subsp. distasonis, 12; B. fragilis subsp. fragilis, 39; B. fragilis subsp. ovatus, 10; B. fragilis subsp. thetaiotaomicron, 32; B. fragilis subsp. vulgatus, 10; and B. fragilis subsp. \"other,\" 12. There were no marked differences in susceptibility between the subspecies. One strain of B. fragilis subsp. thetaiotaomicron had a minimal inhibitory concentration of 12.5 mug/ml for clindamycin, but all other strains were susceptible. All the strains were susceptible to chloramphenicol. Susceptibility to tetracycline was variable. Only a few strains were susceptible to the penicillins and cephalothin.", "contents": "Antibiotic susceptibility of the subspecies of Bacteroides fragilis. Strains (115) of Bacteroides fragilis were identified at the subspecific level and were tested for susceptibility to ampicillin, cephalothin, chloramphenicol, clindamycin, penicillin, and tetracycline using an agar dilution technique. We tested the following strains: B. fragilis subsp. distasonis, 12; B. fragilis subsp. fragilis, 39; B. fragilis subsp. ovatus, 10; B. fragilis subsp. thetaiotaomicron, 32; B. fragilis subsp. vulgatus, 10; and B. fragilis subsp. \"other,\" 12. There were no marked differences in susceptibility between the subspecies. One strain of B. fragilis subsp. thetaiotaomicron had a minimal inhibitory concentration of 12.5 mug/ml for clindamycin, but all other strains were susceptible. All the strains were susceptible to chloramphenicol. Susceptibility to tetracycline was variable. Only a few strains were susceptible to the penicillins and cephalothin."} {"id": "PMID:1259404", "title": "Use of clindamycin in patients with liver disease.", "content": "Hepatotoxicity has been noted by several investigators during parenteral use of clindamycin, and some have reported that drug half-life is prolonged in the presence of liver disease. We administered 300 mg of clindamycin intravenously at 12-h intervals for 2 days to patients with acute and chronic hepatitis, cirrhosis, and controls to determine whether clindamycin will exacerbate preexisting hepatic dysfunction or whether drug excretion will be delayed in patients with liver disease as compared with controls. Exacerbation of hepatotoxicity was not found in this study. There was a small, but significant, delay in drug elimination between cirrhotics and controls, even after the first dose of clindamycin (P < 0.05); however, half-lives in all categories were in the range usually considered normal. We conclude that clindamycin can be used in liver disease in some circumstances, if proper precautions are exercised.", "contents": "Use of clindamycin in patients with liver disease. Hepatotoxicity has been noted by several investigators during parenteral use of clindamycin, and some have reported that drug half-life is prolonged in the presence of liver disease. We administered 300 mg of clindamycin intravenously at 12-h intervals for 2 days to patients with acute and chronic hepatitis, cirrhosis, and controls to determine whether clindamycin will exacerbate preexisting hepatic dysfunction or whether drug excretion will be delayed in patients with liver disease as compared with controls. Exacerbation of hepatotoxicity was not found in this study. There was a small, but significant, delay in drug elimination between cirrhotics and controls, even after the first dose of clindamycin (P < 0.05); however, half-lives in all categories were in the range usually considered normal. We conclude that clindamycin can be used in liver disease in some circumstances, if proper precautions are exercised."} {"id": "PMID:1259405", "title": "Efficacy of cinoxacin in urinary tract infections.", "content": "Cinoxacin, a new synthetic antibacterial agent with in vitro activity against all species of Enterobacteriaceae, was used in the treatment of urinary tract infections in 20 patients. The dose of cinoxacin was 250 mg orally every 6 h for 10 days. The etiological agents were Escherichia coli in fifteen, Klebsiella-Enterobacter in five, Proteus mirabilis in two, and Providencia in one. The minimal inhibitory concentration for these organisms ranged from 2 to 64 mug/ml. Eleven of the 20 patients had renal involvement by defined criteria, whereas the remaining nine were considered to have bladder bacilluria. The initial strain was eradicated during and immediately after treatment in 19 of 20 cases. At 6 weeks, 65% had sterile urine. Bactericidal urine levels of cinoxacin were obtained in all patients. No significant hematological, renal, hepatic, or gastroenterologic toxicity was noted. Cinoxacin appears to be a safe and useful drug in the treatment of urinary tract infections caused by Enterobacteriaceae.", "contents": "Efficacy of cinoxacin in urinary tract infections. Cinoxacin, a new synthetic antibacterial agent with in vitro activity against all species of Enterobacteriaceae, was used in the treatment of urinary tract infections in 20 patients. The dose of cinoxacin was 250 mg orally every 6 h for 10 days. The etiological agents were Escherichia coli in fifteen, Klebsiella-Enterobacter in five, Proteus mirabilis in two, and Providencia in one. The minimal inhibitory concentration for these organisms ranged from 2 to 64 mug/ml. Eleven of the 20 patients had renal involvement by defined criteria, whereas the remaining nine were considered to have bladder bacilluria. The initial strain was eradicated during and immediately after treatment in 19 of 20 cases. At 6 weeks, 65% had sterile urine. Bactericidal urine levels of cinoxacin were obtained in all patients. No significant hematological, renal, hepatic, or gastroenterologic toxicity was noted. Cinoxacin appears to be a safe and useful drug in the treatment of urinary tract infections caused by Enterobacteriaceae."} {"id": "PMID:1259406", "title": "Comparative study of the in vitro antibacterial activity of cefoxitin, cefuroxine, and cephaloridine.", "content": "The in vitro antibacterial effects of cefoxitin, a semisynthetic cephamycin, cefuroxime, a new cephalosporin antibiotic, and cephaloridine were compared. With gram-positive bacteria, marked differences were found only in the effects against Streptococcus faecalis, where cephaloridine and cefuroxime were superior to cefoxitin. With gram-negative aerobic bacteria, cefoxitin, which is known to be more resistant to beta-lactamases from gram-negative bacteria than any cephalosporin, was found to be more effective than cefuroxime and cephaloridine against ampicillin-resistant strains of Escherichia coli and indole-positive strains of Proteus. Haemophilus influenzae was found to be more susceptible to cefuroxime than to cefoxitin and cephaloridine. When ampicillin-resistant strains of H. influenzae were tested, markedly higher minimal inhibitory concentration values were obtained with cephaloridine in comparison to those obtained with ampicillin-susceptible strains. These increases in the minimal inhibitory concentration values were not observed with cefoxitin and cefuroxime, probably due to the resistance of these two compounds to beta-lactamases. Strains of Bacteroides fragilis were found to be much more susceptible to cefoxitin than to cefuroxime, which in turn was superior to cephaloridine. The results obtained indicate that cefoxitin and cefuroxime both are superior in their antibacterial spectra to the cephalosporins that are now in clinical use.", "contents": "Comparative study of the in vitro antibacterial activity of cefoxitin, cefuroxine, and cephaloridine. The in vitro antibacterial effects of cefoxitin, a semisynthetic cephamycin, cefuroxime, a new cephalosporin antibiotic, and cephaloridine were compared. With gram-positive bacteria, marked differences were found only in the effects against Streptococcus faecalis, where cephaloridine and cefuroxime were superior to cefoxitin. With gram-negative aerobic bacteria, cefoxitin, which is known to be more resistant to beta-lactamases from gram-negative bacteria than any cephalosporin, was found to be more effective than cefuroxime and cephaloridine against ampicillin-resistant strains of Escherichia coli and indole-positive strains of Proteus. Haemophilus influenzae was found to be more susceptible to cefuroxime than to cefoxitin and cephaloridine. When ampicillin-resistant strains of H. influenzae were tested, markedly higher minimal inhibitory concentration values were obtained with cephaloridine in comparison to those obtained with ampicillin-susceptible strains. These increases in the minimal inhibitory concentration values were not observed with cefoxitin and cefuroxime, probably due to the resistance of these two compounds to beta-lactamases. Strains of Bacteroides fragilis were found to be much more susceptible to cefoxitin than to cefuroxime, which in turn was superior to cephaloridine. The results obtained indicate that cefoxitin and cefuroxime both are superior in their antibacterial spectra to the cephalosporins that are now in clinical use."} {"id": "PMID:1259407", "title": "Cefuroxime, a new cephalosporin antibiotic: activity in vitro.", "content": "Cefuroxime is a new broad-spectrum cephalosporin antibiotic with increased stability to beta-lactamases. This stability, although no absolute in all cases, has the effect of widening the antibacterial spectrum of the compound so that many organisms resistant to the established cephalosporins are susceptible to cefuroxime. It is active against gram-positive organisms, including penicillinase-producing staphylococci, but it is less active against methicillin-resistant strains. In addition to its high activity against non-beta-lactamase-producing gram-negative bacteria, cefuroxime effectively inhibits the growth of many beta-lactamase-producing strains, including Enterobacter, Klebsiella, and indole-positive Proteus spp. It is highly active against Neisseria gonorrhoeae, Neisseria meningitidis, and also Haemophilus influenzae, including ampicillin-resistant strains. Cefuroxime is rapidly bactericidal and induces the formation and subsequent lysis of filamentous forms over a small concentration range.", "contents": "Cefuroxime, a new cephalosporin antibiotic: activity in vitro. Cefuroxime is a new broad-spectrum cephalosporin antibiotic with increased stability to beta-lactamases. This stability, although no absolute in all cases, has the effect of widening the antibacterial spectrum of the compound so that many organisms resistant to the established cephalosporins are susceptible to cefuroxime. It is active against gram-positive organisms, including penicillinase-producing staphylococci, but it is less active against methicillin-resistant strains. In addition to its high activity against non-beta-lactamase-producing gram-negative bacteria, cefuroxime effectively inhibits the growth of many beta-lactamase-producing strains, including Enterobacter, Klebsiella, and indole-positive Proteus spp. It is highly active against Neisseria gonorrhoeae, Neisseria meningitidis, and also Haemophilus influenzae, including ampicillin-resistant strains. Cefuroxime is rapidly bactericidal and induces the formation and subsequent lysis of filamentous forms over a small concentration range."} {"id": "PMID:1259408", "title": "Cefuroxime, a new cephalosporin antibiotic: activity in vivo.", "content": "The pharmacokinetic properties of cefuroxime have been evaluated in laboratory animals. On injection into mice, rats, and rabbits by the subcutaneous or intramuscular routes, high serum level peaks were recorded. There was no significant absorption after oral administration. After injection, the antibiotic was excreted in large amounts in the urine. It was well distributed in the body and penetrated into the tissues at a satisfactory rate. This, coupled with a low degree of serum protein binding, was correlated with a very good protective effect in animals (mice, rats, and rabbits) experimentally infected with a wide range of bacteria, including beta-lactamase-producing strains. It is concluded that cefuroxime should have a good potential for treating a wide range of bacterial infections in humans.", "contents": "Cefuroxime, a new cephalosporin antibiotic: activity in vivo. The pharmacokinetic properties of cefuroxime have been evaluated in laboratory animals. On injection into mice, rats, and rabbits by the subcutaneous or intramuscular routes, high serum level peaks were recorded. There was no significant absorption after oral administration. After injection, the antibiotic was excreted in large amounts in the urine. It was well distributed in the body and penetrated into the tissues at a satisfactory rate. This, coupled with a low degree of serum protein binding, was correlated with a very good protective effect in animals (mice, rats, and rabbits) experimentally infected with a wide range of bacteria, including beta-lactamase-producing strains. It is concluded that cefuroxime should have a good potential for treating a wide range of bacterial infections in humans."} {"id": "PMID:1259409", "title": "Effects of sesquiterpene lactones on the growth of Bacillus thuringiensis.", "content": "Two sesquiterpene lactones, hymenovin and tenulin, were tested for their effect on growth of two strains of Bacillus thuringiensis. Growth of both strains was 98% inhibited by 0.6 mg of tenulin per ml, but only 15 to 20% was inhibited by the same level of hymenovin. Hymenovin appeared to have a mutagenic effect on B. thuringiensis cultures resulting in production of several variant strains. Some of the variant strains had lost their ability to form spores and crystals. Hymenovin also induced B. thuringiensis to produce significant levels of bacteriophage. All variant strains were as susceptible to phage as the parent strain. Although the bactericidal activity of tenulin was two times as great as of hymenovin, tenulin did not appear to have a mutagenic effect on the bacteria.", "contents": "Effects of sesquiterpene lactones on the growth of Bacillus thuringiensis. Two sesquiterpene lactones, hymenovin and tenulin, were tested for their effect on growth of two strains of Bacillus thuringiensis. Growth of both strains was 98% inhibited by 0.6 mg of tenulin per ml, but only 15 to 20% was inhibited by the same level of hymenovin. Hymenovin appeared to have a mutagenic effect on B. thuringiensis cultures resulting in production of several variant strains. Some of the variant strains had lost their ability to form spores and crystals. Hymenovin also induced B. thuringiensis to produce significant levels of bacteriophage. All variant strains were as susceptible to phage as the parent strain. Although the bactericidal activity of tenulin was two times as great as of hymenovin, tenulin did not appear to have a mutagenic effect on the bacteria."} {"id": "PMID:1259410", "title": "Comparison of the binding of penicillin G to staphylococcal L-form and its parent strain membranes.", "content": "The binding of penicillin G to a stable L-form from Staphylococcus aureus followed saturation-type kinetics with saturation achieved at 0.75 nmol/ml, the same as with its parent strain.", "contents": "Comparison of the binding of penicillin G to staphylococcal L-form and its parent strain membranes. The binding of penicillin G to a stable L-form from Staphylococcus aureus followed saturation-type kinetics with saturation achieved at 0.75 nmol/ml, the same as with its parent strain."} {"id": "PMID:1259411", "title": "Inhibition of bacterial growth by the nitrofurantoin solvent dimethylformamide.", "content": "For quantitative susceptibility tests, stock solutions of nitrofurantoin are often prepared in dimethylformamide. Since 1.0 or 2.0 ml of the solvent will inhibit microbial growth, currently recommended procedures for antimicrobic dilution tests should be modified by adding only 0.1 or 0.2 ml of stock drug solutions to the agar or broth medium.", "contents": "Inhibition of bacterial growth by the nitrofurantoin solvent dimethylformamide. For quantitative susceptibility tests, stock solutions of nitrofurantoin are often prepared in dimethylformamide. Since 1.0 or 2.0 ml of the solvent will inhibit microbial growth, currently recommended procedures for antimicrobic dilution tests should be modified by adding only 0.1 or 0.2 ml of stock drug solutions to the agar or broth medium."} {"id": "PMID:1259412", "title": "Enhancement of rIn:rCn-induced interferon production by amphotericin B.", "content": "When mouse L929 cells are treated with amphotericin B before exposure to polyriboinosinic-polyribocytidylic acid or polyriboinosinic-polyribocytidylic acid-dextran, they make significantly more interferon than do cells not receiving amphotericin. This effect may be due to enhanced cell membrane penetration by the polynucleotide.", "contents": "Enhancement of rIn:rCn-induced interferon production by amphotericin B. When mouse L929 cells are treated with amphotericin B before exposure to polyriboinosinic-polyribocytidylic acid or polyriboinosinic-polyribocytidylic acid-dextran, they make significantly more interferon than do cells not receiving amphotericin. This effect may be due to enhanced cell membrane penetration by the polynucleotide."} {"id": "PMID:1259413", "title": "Nafcillin treatment of Staphylococcus aureus meningitis.", "content": "Serial serum and cerebrospinal fluid nafcillin concentrations were determined in a patient successfully treated with nafcillin (200 mg/kg per day) for Staphylococcus aureus bacteremia and meningitis. Nafcillin and methicillin cerebrospinal fluid concentrations were compared.", "contents": "Nafcillin treatment of Staphylococcus aureus meningitis. Serial serum and cerebrospinal fluid nafcillin concentrations were determined in a patient successfully treated with nafcillin (200 mg/kg per day) for Staphylococcus aureus bacteremia and meningitis. Nafcillin and methicillin cerebrospinal fluid concentrations were compared."} {"id": "PMID:1259445", "title": "Factors influencing methoxsalen phototoxicity in vitiliginous skin.", "content": "A series of experiments were conducted to determine the optimum conditions required to induce methoxsalen phototoxicity in vitiliginous skin. The results revealed that optimum phototoxicity could be obtained only when a lapse of at least 15 minutes was allowed between the application of the drug and exposure to long-wave ultraviolet light (UVA). The duration of methoxsalen's phototoxic potentially, after its application to skin, varied in direct proportion to chemical concentration. Although a high chemical concentration and low dosage of UVA was a less time-consuming method of inducing phototoxicity, our results indicate that lower concentration and longer UVA exposure were less likely to induce undersirable blistering reactions.", "contents": "Factors influencing methoxsalen phototoxicity in vitiliginous skin. A series of experiments were conducted to determine the optimum conditions required to induce methoxsalen phototoxicity in vitiliginous skin. The results revealed that optimum phototoxicity could be obtained only when a lapse of at least 15 minutes was allowed between the application of the drug and exposure to long-wave ultraviolet light (UVA). The duration of methoxsalen's phototoxic potentially, after its application to skin, varied in direct proportion to chemical concentration. Although a high chemical concentration and low dosage of UVA was a less time-consuming method of inducing phototoxicity, our results indicate that lower concentration and longer UVA exposure were less likely to induce undersirable blistering reactions."} {"id": "PMID:1259446", "title": "Pruritic skin diseases, psychological stress, and the itch sensation. A reliable method for the induction of experimental pruritus.", "content": "A method of inducing controlled levels of terminable itching was developed. This method consists of administering constant monophasic pulsations of electric current by means of noninvasive electrodes. Once experimental pruritus had been reliably reproduced, two variables, hypothesized to be relevant to the perception of itching, were investigated, viz, the presence of a positive or a negative history of a pruritic dermatosis, and the presence of a high or low level of psychological stress. Both variables were found to be related to the perception of itching, but in different manners. A positive history of a pruritic dermatosis lowered the threshold for the perception of itch stimuli, while a high level of psychological stress enhanced the ability to discriminate among the more intense itch stimuli, with no effect on the itch threshold.", "contents": "Pruritic skin diseases, psychological stress, and the itch sensation. A reliable method for the induction of experimental pruritus. A method of inducing controlled levels of terminable itching was developed. This method consists of administering constant monophasic pulsations of electric current by means of noninvasive electrodes. Once experimental pruritus had been reliably reproduced, two variables, hypothesized to be relevant to the perception of itching, were investigated, viz, the presence of a positive or a negative history of a pruritic dermatosis, and the presence of a high or low level of psychological stress. Both variables were found to be related to the perception of itching, but in different manners. A positive history of a pruritic dermatosis lowered the threshold for the perception of itch stimuli, while a high level of psychological stress enhanced the ability to discriminate among the more intense itch stimuli, with no effect on the itch threshold."} {"id": "PMID:1259447", "title": "Clofazimine. A new agent for the treatment of pyoderma gangrenosum.", "content": "Eight patients had pyoderma gangrenosum. They were given a phendimetrazine tartrate derivative, clofazimine (Lamprene [Britain]), which is a chemotherapeutic agent used mainly in certain mycobacterial infections and which also has phagocytosis-enhancing properties. The effect of this drug was remarkably good, with rapid healing of the lesions commencing 3 to 14 days after treatment was started. The mechanism for the effect of clofazimine in pyoderma gangrenosum is not known.", "contents": "Clofazimine. A new agent for the treatment of pyoderma gangrenosum. Eight patients had pyoderma gangrenosum. They were given a phendimetrazine tartrate derivative, clofazimine (Lamprene [Britain]), which is a chemotherapeutic agent used mainly in certain mycobacterial infections and which also has phagocytosis-enhancing properties. The effect of this drug was remarkably good, with rapid healing of the lesions commencing 3 to 14 days after treatment was started. The mechanism for the effect of clofazimine in pyoderma gangrenosum is not known."} {"id": "PMID:1259448", "title": "Malignant atrophic papulosis (Degros disease). A report of two cases with clinical and histological studies.", "content": "Two women had malignant atrophic papulosis that affected the skin only. Immunologic studies showed normal amounts of serum immunoglobulins and complement and normal delayed hypersensitivity skin test results. Fibrinolysis autografts showed complete loss of fibrinolysis within the lesions but normal fibrinolysis in uninvolved skin. Histopathologic studies showed moderate inflammatory infiltration consisting of lymphocytes in addition to the typical cone-shaped regions of necrobiosis. Large amounts of mucin also were seen. Endovasculitis, thrombosis, and perivascular lymphocytic inflammation were noted in the subcutaneous arterioles of the lesions in only one of the patients. Enzyme histochemical studies showed oxidative enzymes, although in reduced amounts, in the epidermal and dermal cells of the affected skin. Electron microscopic studies of lesions showed paromyxovirus-like inclusions in endothelial cells and fibroblasts. The possibility of an unusual viral causation should be examined further.", "contents": "Malignant atrophic papulosis (Degros disease). A report of two cases with clinical and histological studies. Two women had malignant atrophic papulosis that affected the skin only. Immunologic studies showed normal amounts of serum immunoglobulins and complement and normal delayed hypersensitivity skin test results. Fibrinolysis autografts showed complete loss of fibrinolysis within the lesions but normal fibrinolysis in uninvolved skin. Histopathologic studies showed moderate inflammatory infiltration consisting of lymphocytes in addition to the typical cone-shaped regions of necrobiosis. Large amounts of mucin also were seen. Endovasculitis, thrombosis, and perivascular lymphocytic inflammation were noted in the subcutaneous arterioles of the lesions in only one of the patients. Enzyme histochemical studies showed oxidative enzymes, although in reduced amounts, in the epidermal and dermal cells of the affected skin. Electron microscopic studies of lesions showed paromyxovirus-like inclusions in endothelial cells and fibroblasts. The possibility of an unusual viral causation should be examined further."} {"id": "PMID:1259449", "title": "Cutaneous manifestations of familial Mediterranean fever.", "content": "Familial Mediterranean fever (FMF) is frequently accompanied by erysipelas-like attacks. These should alert the physician to the correct diagnosis of this systemic disease. Several other nonspecific skin lesions may be seen in FMF. To our knowledge, histologic findings in erysipelas-like skin rashes seen in FMF are not reported elsewhere in the literature.", "contents": "Cutaneous manifestations of familial Mediterranean fever. Familial Mediterranean fever (FMF) is frequently accompanied by erysipelas-like attacks. These should alert the physician to the correct diagnosis of this systemic disease. Several other nonspecific skin lesions may be seen in FMF. To our knowledge, histologic findings in erysipelas-like skin rashes seen in FMF are not reported elsewhere in the literature."} {"id": "PMID:1259450", "title": "Disseminated Nocardia brasiliensis infection.", "content": "We report a 40-year-old man with advanced Hodgkin disease who received combination chemotherapy and developed disseminated Nocardia brasiliensis infection. We discuss opportunistic infections in the compromised host, with particular reference to nocardial disease and certain biologic characteristics of that organism.", "contents": "Disseminated Nocardia brasiliensis infection. We report a 40-year-old man with advanced Hodgkin disease who received combination chemotherapy and developed disseminated Nocardia brasiliensis infection. We discuss opportunistic infections in the compromised host, with particular reference to nocardial disease and certain biologic characteristics of that organism."} {"id": "PMID:1259451", "title": "Molecular mechanisms of genetic disorders of keratinization.", "content": "An attempt is made to organize our current knowledge about genetically determined disorders of keratinized tissue, which primarily affect the epidermal structural proteins. Type I defects are those involving a change in a single amino acid and are analogous to sickle cell anemia. Type II defects are associated with abnormal retention of a normal structural protein intermediate. Type III defects are related to alterations in the normal post-translational cross-linking seen in keratinized tissues. Type IV defects are associated with altered proportions of fibrous proteins and are analogous to thalassemia. In type V defects, primary genetic disorders of other tissues profoundly affect keratinization in a secondary fashion. Examples from genetic disorders of the hair and epidermis are used to build this conceptual scheme.", "contents": "Molecular mechanisms of genetic disorders of keratinization. An attempt is made to organize our current knowledge about genetically determined disorders of keratinized tissue, which primarily affect the epidermal structural proteins. Type I defects are those involving a change in a single amino acid and are analogous to sickle cell anemia. Type II defects are associated with abnormal retention of a normal structural protein intermediate. Type III defects are related to alterations in the normal post-translational cross-linking seen in keratinized tissues. Type IV defects are associated with altered proportions of fibrous proteins and are analogous to thalassemia. In type V defects, primary genetic disorders of other tissues profoundly affect keratinization in a secondary fashion. Examples from genetic disorders of the hair and epidermis are used to build this conceptual scheme."} {"id": "PMID:1259455", "title": "Sick sinus syndrome in children.", "content": "The ages of 6 male patients with the sick sinus syndrome ranged from 10-15 years when their symptoms began. At rest all had a heart rate of 60/min or less. Two had syncopal attacks which threatened life; 1 had only attacks of dizziness; the other 3 had no syncopal attacks but had recurrent attacks of supraventricular tachycardia ('brady-tachycardia syndrome') which were more resistant to drug therapy than is usual in childhood. They were not controlled or suppressed by digoxin when it was given. Substernal pain occurred in 2 patients who had syncope. In all patients the heart rate remained inappropriately slow after exercise and atropine. Cardiac pacemakers were used in the 2 patients with life-threatening syncope. Any patient who has dizziness or syncopal attacks and an inappropriately slow heart rate should have electrocardiograms recorded at rest and after exercise to record the heart rate and to look for abnormal P-waves.", "contents": "Sick sinus syndrome in children. The ages of 6 male patients with the sick sinus syndrome ranged from 10-15 years when their symptoms began. At rest all had a heart rate of 60/min or less. Two had syncopal attacks which threatened life; 1 had only attacks of dizziness; the other 3 had no syncopal attacks but had recurrent attacks of supraventricular tachycardia ('brady-tachycardia syndrome') which were more resistant to drug therapy than is usual in childhood. They were not controlled or suppressed by digoxin when it was given. Substernal pain occurred in 2 patients who had syncope. In all patients the heart rate remained inappropriately slow after exercise and atropine. Cardiac pacemakers were used in the 2 patients with life-threatening syncope. Any patient who has dizziness or syncopal attacks and an inappropriately slow heart rate should have electrocardiograms recorded at rest and after exercise to record the heart rate and to look for abnormal P-waves."} {"id": "PMID:1259456", "title": "Hereditary tyrosinaemia. Clinical, enzymatic, and pathological study of an infant with the acute form of the disease.", "content": "A clinical, enzymatic, and pathological study of an infant with the acute form of hereditary tyrosinaemia is presented. Treatment with a diet low in methionine, tyrosine, and phenylalanine was unsuccessful. A selection of specific and nonspecific hepatic enzymes, obtained at necropsy within one hour of the infant's death at 9 1/2 weeks, were studied to try to throw light on the basic defect. The major pathological findings were those of a peculiar hepatic fibrosis associated with bile retention and an abnormal grouping of hepatocytes, islet-cell hyperplasia of the pancreas, and dilatation of the proximal renal tubules. Death was precipitated by bronchopneumonia and liver failure. The difficulty in diagnosing the acute form of tyrosinaemia is pointed out, especially in differentiating it from hereditary galactosaemia (transferase deficiency) and hereditary fructosaemia. All three may present with the same clinical symptoms and liver lesions, and the distinction must be made by enzyme studies and by therapeutic trial.", "contents": "Hereditary tyrosinaemia. Clinical, enzymatic, and pathological study of an infant with the acute form of the disease. A clinical, enzymatic, and pathological study of an infant with the acute form of hereditary tyrosinaemia is presented. Treatment with a diet low in methionine, tyrosine, and phenylalanine was unsuccessful. A selection of specific and nonspecific hepatic enzymes, obtained at necropsy within one hour of the infant's death at 9 1/2 weeks, were studied to try to throw light on the basic defect. The major pathological findings were those of a peculiar hepatic fibrosis associated with bile retention and an abnormal grouping of hepatocytes, islet-cell hyperplasia of the pancreas, and dilatation of the proximal renal tubules. Death was precipitated by bronchopneumonia and liver failure. The difficulty in diagnosing the acute form of tyrosinaemia is pointed out, especially in differentiating it from hereditary galactosaemia (transferase deficiency) and hereditary fructosaemia. All three may present with the same clinical symptoms and liver lesions, and the distinction must be made by enzyme studies and by therapeutic trial."} {"id": "PMID:1259457", "title": "Neonatal screening for haemoglobinopathy. Results in 7691 Manchester newborns.", "content": "Over a period of one year the blood samples collected for phenylketonuria testing from 7691 Manchester newborns were screened by haemoglobin electrophoresis. An abnormality was detected in 47 (0-61%) of the babies. No cases of homozygous haemoglobinopathy were found. The overall incidence of sickle-cell trait was 0-38%, but for the Black population it was 10%. Four Black babies and one White baby had alpha-thalassaemia. No other haemoglobinopathies were found in the White babies and no Asian baby had alpha-thalassaemia. Haemoglobin A2 was precociously developed in three babies, two of whom were coloured--probably a further example of the earlier maturity of coloured babies. The screening programme was stopped when it became cleaasily be combined with screening for metabolic disease in places where the incidence of haemoglobinopathies is higher.", "contents": "Neonatal screening for haemoglobinopathy. Results in 7691 Manchester newborns. Over a period of one year the blood samples collected for phenylketonuria testing from 7691 Manchester newborns were screened by haemoglobin electrophoresis. An abnormality was detected in 47 (0-61%) of the babies. No cases of homozygous haemoglobinopathy were found. The overall incidence of sickle-cell trait was 0-38%, but for the Black population it was 10%. Four Black babies and one White baby had alpha-thalassaemia. No other haemoglobinopathies were found in the White babies and no Asian baby had alpha-thalassaemia. Haemoglobin A2 was precociously developed in three babies, two of whom were coloured--probably a further example of the earlier maturity of coloured babies. The screening programme was stopped when it became cleaasily be combined with screening for metabolic disease in places where the incidence of haemoglobinopathies is higher."} {"id": "PMID:1259458", "title": "Follow-up of children of drug-addicted mothers.", "content": "During a period of 2 years (1971-72) 19 newborn infants were admitted to hospital because their mothers were drug addicts. To evaluate the prognosis in these children, 17 were followed up by a social adviser, a psychologist, and a paediatrician. During the neonatal period 16 of the infants had withdrawal symptoms, for which 11 required medical treatment. One infant died of congenital malformations. Of the surviving 18 infants 14 were discharged to their mothers and 4 went to a children's home. During follow-up, which varied from up to 2 months to up to 2 years 8 months of age, 10 of the children had to be placed in a children's home for a period. No physical abnormalities were found in the children. Motor and perceptual development were normal in 12 but in 3 speech development was delayed. Five mothers ceased to take drugs after delivery and 2 had done so during early pregnancy. The pre- and perinatal complications and the undesirable environment in which the children grow up show the need for a comprehensive treatment programme.", "contents": "Follow-up of children of drug-addicted mothers. During a period of 2 years (1971-72) 19 newborn infants were admitted to hospital because their mothers were drug addicts. To evaluate the prognosis in these children, 17 were followed up by a social adviser, a psychologist, and a paediatrician. During the neonatal period 16 of the infants had withdrawal symptoms, for which 11 required medical treatment. One infant died of congenital malformations. Of the surviving 18 infants 14 were discharged to their mothers and 4 went to a children's home. During follow-up, which varied from up to 2 months to up to 2 years 8 months of age, 10 of the children had to be placed in a children's home for a period. No physical abnormalities were found in the children. Motor and perceptual development were normal in 12 but in 3 speech development was delayed. Five mothers ceased to take drugs after delivery and 2 had done so during early pregnancy. The pre- and perinatal complications and the undesirable environment in which the children grow up show the need for a comprehensive treatment programme."} {"id": "PMID:1259459", "title": "Transient acute myositis in childhood.", "content": "Eight cases of transient acute polymyalgia with weakness are described. All had abnormal serum creatine phosphokinase levels and most had minor haematological abnormalities at the time of diagnosis. Virological studies were performed with negative findings.", "contents": "Transient acute myositis in childhood. Eight cases of transient acute polymyalgia with weakness are described. All had abnormal serum creatine phosphokinase levels and most had minor haematological abnormalities at the time of diagnosis. Virological studies were performed with negative findings."} {"id": "PMID:1259460", "title": "Calcium, magnesium, and glucose levels in blood and CSF of children with febrile convulsions.", "content": "Levels of calcium, magnesium, and glucose were measured in the blood and cerebrospinal fluid (CSF) of children with febrile convulsions. Calcium and magnesium levels were within the normal range and the blood: CSF ratios were similar to those of normal subjects. Hyperglycaemia was a frequent finding and was reflected in raised CSF glucose levels. Blood glucose levels were only transiently raised and none of the children had diabetes mellitus.", "contents": "Calcium, magnesium, and glucose levels in blood and CSF of children with febrile convulsions. Levels of calcium, magnesium, and glucose were measured in the blood and cerebrospinal fluid (CSF) of children with febrile convulsions. Calcium and magnesium levels were within the normal range and the blood: CSF ratios were similar to those of normal subjects. Hyperglycaemia was a frequent finding and was reflected in raised CSF glucose levels. Blood glucose levels were only transiently raised and none of the children had diabetes mellitus."} {"id": "PMID:1259461", "title": "Relation of urinary total hydroxyproline: Creatinine ratio to height velocity in children with retarded growth.", "content": "The urinary total hydroxyproline:creatinine ratio was measured on samples collected from 18 boys and 11 girls referred to a children's hospital because of small stature. Any serious degree of growth hormone deficiency was excluded and each child's growth and development was recorded over the following year. The hypothesis that the average hydroxyproline:creatinine ratio on random urine samples may be used to predict height velocity was examined. Such a prediction would have been incorrect on 35% of occasions, and it is concluded that this investigation cannot be used reliability to predict growth in height; it is probably only useful with sequential studies of an individual child over short periods while monitoring therapy.", "contents": "Relation of urinary total hydroxyproline: Creatinine ratio to height velocity in children with retarded growth. The urinary total hydroxyproline:creatinine ratio was measured on samples collected from 18 boys and 11 girls referred to a children's hospital because of small stature. Any serious degree of growth hormone deficiency was excluded and each child's growth and development was recorded over the following year. The hypothesis that the average hydroxyproline:creatinine ratio on random urine samples may be used to predict height velocity was examined. Such a prediction would have been incorrect on 35% of occasions, and it is concluded that this investigation cannot be used reliability to predict growth in height; it is probably only useful with sequential studies of an individual child over short periods while monitoring therapy."} {"id": "PMID:1259463", "title": "Genetic aspects of nutritional rickets.", "content": "Amino acid excretion was investigated in 21 rachitic infants and in 22 of their parents. There was (a) increased alpha-amino acid excretion in one-third of the infants a long time after the rickets had healed, (b) an abnormally high excretion of alpha-amino nitrogen and of phosphorus in many of the parents (c) an abnormal pattern of amino acid excretion in all 9 infants tested, and (d) a good correlation between the excretion of individual amino acids by an infant and by its parents. Our findings suggest that in at least some cases of nutritional rickets there is a genetic element which may manifest itself only under adverse environmental conditions.", "contents": "Genetic aspects of nutritional rickets. Amino acid excretion was investigated in 21 rachitic infants and in 22 of their parents. There was (a) increased alpha-amino acid excretion in one-third of the infants a long time after the rickets had healed, (b) an abnormally high excretion of alpha-amino nitrogen and of phosphorus in many of the parents (c) an abnormal pattern of amino acid excretion in all 9 infants tested, and (d) a good correlation between the excretion of individual amino acids by an infant and by its parents. Our findings suggest that in at least some cases of nutritional rickets there is a genetic element which may manifest itself only under adverse environmental conditions."} {"id": "PMID:1259464", "title": "[Investigations on the mechanism of the activity of urea upon the epidermis (author's transl)].", "content": "As a reaction of the epidermis subsequent upon contact with urea, a thinning is ascertainable 5 days later, for which corresponding enzymological and autoradiographical findings cause to presume the DNA being the working point. Further information about the mechanism of this reaction was obtained first by short time tests, whence by means of 3H thymidine autoradiography not later than the second day after contact with urea a decreased number of cells synthesizing DNA in the stratum basale were to be secured. These findings obtained using the model of the guinea-pig's ear are also ascertainable in the human skin, an unspecified effect, also to be released by other non-electrolytes, having been excluded by controls of glucose replacing urea. The quick invasion of urea into the epidermis, deducible from the short time tests, was proved by 14C traced urea, ascertainable not later than 15 min after its contact with the skin amongst the blood - even if in little activity. Hence, the urea enters into the cutis speedily, releasing there a disturbance in the process of the epidermal proliferation, which conducts in the sequel to an epidermal thinning.", "contents": "[Investigations on the mechanism of the activity of urea upon the epidermis (author's transl)]. As a reaction of the epidermis subsequent upon contact with urea, a thinning is ascertainable 5 days later, for which corresponding enzymological and autoradiographical findings cause to presume the DNA being the working point. Further information about the mechanism of this reaction was obtained first by short time tests, whence by means of 3H thymidine autoradiography not later than the second day after contact with urea a decreased number of cells synthesizing DNA in the stratum basale were to be secured. These findings obtained using the model of the guinea-pig's ear are also ascertainable in the human skin, an unspecified effect, also to be released by other non-electrolytes, having been excluded by controls of glucose replacing urea. The quick invasion of urea into the epidermis, deducible from the short time tests, was proved by 14C traced urea, ascertainable not later than 15 min after its contact with the skin amongst the blood - even if in little activity. Hence, the urea enters into the cutis speedily, releasing there a disturbance in the process of the epidermal proliferation, which conducts in the sequel to an epidermal thinning."} {"id": "PMID:1259465", "title": "[Reflexphotometric determinations of vasoconstriction after topical application of steroids. IV. Time slope of vasoconstriction and reactive vasodilatation (author's transl)].", "content": "In this study a reflex photometrical technique has been used to examine local steroid induced vasoreactions. When applied but once, steroids cause a maximum vasoconstriction between 8 and 16 h after beginning the test. Followed by a 32 h period, the phase of vasoconstriction is succeeded by a dilatation of dermis blood vessels. It appears, that the stronger the vasocontriction, the smaller the degree of vasodilatation.", "contents": "[Reflexphotometric determinations of vasoconstriction after topical application of steroids. IV. Time slope of vasoconstriction and reactive vasodilatation (author's transl)]. In this study a reflex photometrical technique has been used to examine local steroid induced vasoreactions. When applied but once, steroids cause a maximum vasoconstriction between 8 and 16 h after beginning the test. Followed by a 32 h period, the phase of vasoconstriction is succeeded by a dilatation of dermis blood vessels. It appears, that the stronger the vasocontriction, the smaller the degree of vasodilatation."} {"id": "PMID:1259466", "title": "[Reflexphotometric determinations of vasoconstriction after topical application of steroids. V. Vasoconstriction phaenomenon and tachyphylaxis after repeated steroid application (author's transl)].", "content": "On the basis of reflexphotometrical vasoconstriction tests it is demonstrated, that the intensity of vasoreactions caused by a first topical application of steroids, diminishes rapidly after repeated applications, until there is no response of vessels to a new application. This phaenomenon is know as tachyphylaxis and has been found in all tested glucocorticoids.", "contents": "[Reflexphotometric determinations of vasoconstriction after topical application of steroids. V. Vasoconstriction phaenomenon and tachyphylaxis after repeated steroid application (author's transl)]. On the basis of reflexphotometrical vasoconstriction tests it is demonstrated, that the intensity of vasoreactions caused by a first topical application of steroids, diminishes rapidly after repeated applications, until there is no response of vessels to a new application. This phaenomenon is know as tachyphylaxis and has been found in all tested glucocorticoids."} {"id": "PMID:1259467", "title": "[Immunological demonstration of beta-glucuronidase in eccrine sweat (author's transl)].", "content": "Electrophoretic and immunological investigations on highly concentrated sweat have shown that human eccrine sweat contains 6 different esterases. Two of them were found to hydrolyze naphthol-AS-Bi-beta-D-glucuronide. One of the two glucuronic acid ester splitting enzymes is likely to be a substrate-specific beta-glucuronidase. The other one is a non-specific carboxyl-esterase occurring in numerous organs and glandular secretions. This non-specific enzyme of widespread distribution can be mistaken for beta-glucuronidase because it hydrolyzes glucuronic acid esters as well as other synthetic substrates.", "contents": "[Immunological demonstration of beta-glucuronidase in eccrine sweat (author's transl)]. Electrophoretic and immunological investigations on highly concentrated sweat have shown that human eccrine sweat contains 6 different esterases. Two of them were found to hydrolyze naphthol-AS-Bi-beta-D-glucuronide. One of the two glucuronic acid ester splitting enzymes is likely to be a substrate-specific beta-glucuronidase. The other one is a non-specific carboxyl-esterase occurring in numerous organs and glandular secretions. This non-specific enzyme of widespread distribution can be mistaken for beta-glucuronidase because it hydrolyzes glucuronic acid esters as well as other synthetic substrates."} {"id": "PMID:1259468", "title": "Effect of needle puncture and intradermal fluid injection on epidermal cell kinetics of albino guinea-pig skin.", "content": "The flanks of male albino guinea pigs were used to study the effect of needle puncture with or without intradermal (id) injection of 0.1 ml fluid. The center of the raised bleb was marked and biopsies taken 1,4,8,24,50 and 72 hrs after needle puncture and 1 hr after intraperitoneal (ip) injection of tritiated thymidine (3H-TdR). There were no significant differences in labeling index (LI) or mitotic index (MI) 1 hr after id, ip, or subcutaneous (sc) injection nor in percent labeled mitoses, 7 hrs after id or ip injection. The earliest increase in LI (180% above control) occurred 12 hrs after needle puncture, peaked at 24 hrs (ca. 3X control), and returned to control level by 50 hrs. The area affected had a radius of about 5 mm from the point of needle entry or center of the bleb. Within 12 hrs after needle puncture, there was an increase in labeled cells primarily at the periphery of the bleb area, about 4 mm from the point of needle entry. By 24 hrs, the distribution of labeled cells had moved toward the bleb center (LI = 65%). The first increase in mitoses (MI = 2.5%) was seen 24 hrs after needle puncture. It is concluded that id injection introduces no significant error in LI or MI to 8 hrs after needle puncture. It does, however, trigger many noncycling basal cells into DNA synthesis after 8 hrs, and this may increase the rate of transit of these cells to the granular layer.", "contents": "Effect of needle puncture and intradermal fluid injection on epidermal cell kinetics of albino guinea-pig skin. The flanks of male albino guinea pigs were used to study the effect of needle puncture with or without intradermal (id) injection of 0.1 ml fluid. The center of the raised bleb was marked and biopsies taken 1,4,8,24,50 and 72 hrs after needle puncture and 1 hr after intraperitoneal (ip) injection of tritiated thymidine (3H-TdR). There were no significant differences in labeling index (LI) or mitotic index (MI) 1 hr after id, ip, or subcutaneous (sc) injection nor in percent labeled mitoses, 7 hrs after id or ip injection. The earliest increase in LI (180% above control) occurred 12 hrs after needle puncture, peaked at 24 hrs (ca. 3X control), and returned to control level by 50 hrs. The area affected had a radius of about 5 mm from the point of needle entry or center of the bleb. Within 12 hrs after needle puncture, there was an increase in labeled cells primarily at the periphery of the bleb area, about 4 mm from the point of needle entry. By 24 hrs, the distribution of labeled cells had moved toward the bleb center (LI = 65%). The first increase in mitoses (MI = 2.5%) was seen 24 hrs after needle puncture. It is concluded that id injection introduces no significant error in LI or MI to 8 hrs after needle puncture. It does, however, trigger many noncycling basal cells into DNA synthesis after 8 hrs, and this may increase the rate of transit of these cells to the granular layer."} {"id": "PMID:1259471", "title": "Protein leakage in the lungs of mice exposed to 0.5 ppm nitrogen dioxide.", "content": "Forty-four mice were continuously exposed to 0.47 ppm nitrogen dioxide for ten, 12, and 14 days. The protein content of homogenized lung tissue was assayed fluorometrically after the animals had received intravenous injections of fluorescamine, a new reagent for protein assay. The mean protein value of all exposed animals was higher than that of the control animals (P less than .025). No correlation was noted between serum fluorophor levels and those in the lung homogenate.", "contents": "Protein leakage in the lungs of mice exposed to 0.5 ppm nitrogen dioxide. Forty-four mice were continuously exposed to 0.47 ppm nitrogen dioxide for ten, 12, and 14 days. The protein content of homogenized lung tissue was assayed fluorometrically after the animals had received intravenous injections of fluorescamine, a new reagent for protein assay. The mean protein value of all exposed animals was higher than that of the control animals (P less than .025). No correlation was noted between serum fluorophor levels and those in the lung homogenate."} {"id": "PMID:1259472", "title": "Mortality in 1969 from pesticides, including aerosols.", "content": "Among the 87 deaths in the United States in 1969 for which a causal relationship to pesticides could not be excluded, there were 62 valid accidents, 20 intentionally inflicted deaths, and five deaths incorrectly attributed to pesticides. The reduction in the number of such deaths compared to the decade and a half prior to 1962 probably involves a trend. As in the past, a disproportionate fraction of the victims were children, boys and men, and nonwhites. Findings in four cases (three in 1969) were consistent with the conclusion that intensive inhalation of an aerosol can sensitize the heart to fatal arrhythmia, even though there is no intentional misuse of the aerosol and no attempt to seek a thrill. Medical examiners should be alert to the possibility of such deaths associated with both pesticide and non-pesticide aerosols.", "contents": "Mortality in 1969 from pesticides, including aerosols. Among the 87 deaths in the United States in 1969 for which a causal relationship to pesticides could not be excluded, there were 62 valid accidents, 20 intentionally inflicted deaths, and five deaths incorrectly attributed to pesticides. The reduction in the number of such deaths compared to the decade and a half prior to 1962 probably involves a trend. As in the past, a disproportionate fraction of the victims were children, boys and men, and nonwhites. Findings in four cases (three in 1969) were consistent with the conclusion that intensive inhalation of an aerosol can sensitize the heart to fatal arrhythmia, even though there is no intentional misuse of the aerosol and no attempt to seek a thrill. Medical examiners should be alert to the possibility of such deaths associated with both pesticide and non-pesticide aerosols."} {"id": "PMID:1259470", "title": "Electron microprobe analysis of particle deposited in lungs.", "content": "A technique that is based on the combined use of a conventional transmission electron microscope and a conventional electron probe x-ray microanalyzer permits an unambiguous identification of titanium dioxide (TiO2) particles in lung tissue and cells. Quite probably, many other inorganic particles can be identified with the use of this technique.", "contents": "Electron microprobe analysis of particle deposited in lungs. A technique that is based on the combined use of a conventional transmission electron microscope and a conventional electron probe x-ray microanalyzer permits an unambiguous identification of titanium dioxide (TiO2) particles in lung tissue and cells. Quite probably, many other inorganic particles can be identified with the use of this technique."} {"id": "PMID:1259477", "title": "Histologic fate and endothelial changes of distended and nondistended vein grafts.", "content": "Sixty-two autogenous cephalic vein segments were grafted into the femoral arteries of 31 mongrel dogs, the left side receiving non-distended (control) grafts and the right side distended (experimental) grafts. Distending media were heparinized blood and saline. Veins were distended at 600 mm Hg for 2 minutes. Specimens were taken at intervals from 15 minutes to 3 months, and were studied by gross inspection, surface observations (light scanning stereoscope to X70 scanning electron microscope to X6,000) and routine histologic techniques (light microscope to X 1000). In general, grafting of veins in the arterial system was followed by progressive degenerative changes in all layers of the vein, including endothelial cell involution, desquamation and re-endothelialization. Often a variable degree of subendothelial fibrous and/or myoepithelial proliferation occurred which might compromise even a lumen lined by healthy endothelium. Distention caused these changes to occur earlier (2-4 weeks) and to be more pronounced. Distention with saline caused more damage to the endothelium than did distention with blood. We conclude that preimplant distention of vein grafts (to overcome spasm) should be employed sparingly, as it adversely affects the endothelial covering of the flow surface, accelerates the development of degenerative changes, and may predispose the graft to early thrombotic complications.", "contents": "Histologic fate and endothelial changes of distended and nondistended vein grafts. Sixty-two autogenous cephalic vein segments were grafted into the femoral arteries of 31 mongrel dogs, the left side receiving non-distended (control) grafts and the right side distended (experimental) grafts. Distending media were heparinized blood and saline. Veins were distended at 600 mm Hg for 2 minutes. Specimens were taken at intervals from 15 minutes to 3 months, and were studied by gross inspection, surface observations (light scanning stereoscope to X70 scanning electron microscope to X6,000) and routine histologic techniques (light microscope to X 1000). In general, grafting of veins in the arterial system was followed by progressive degenerative changes in all layers of the vein, including endothelial cell involution, desquamation and re-endothelialization. Often a variable degree of subendothelial fibrous and/or myoepithelial proliferation occurred which might compromise even a lumen lined by healthy endothelium. Distention caused these changes to occur earlier (2-4 weeks) and to be more pronounced. Distention with saline caused more damage to the endothelium than did distention with blood. We conclude that preimplant distention of vein grafts (to overcome spasm) should be employed sparingly, as it adversely affects the endothelial covering of the flow surface, accelerates the development of degenerative changes, and may predispose the graft to early thrombotic complications."} {"id": "PMID:1259473", "title": "Initial occupational exposure to lead: Chromosome and Biochemical findings.", "content": "Serial chromosome and biochemical studies were carried out in 11 subjects before and during initial occupational exposure to moderate quantities of lead fumes in a storage battery plant. The rate of abnormal metaphases, mostly with chromatid and one-break chromosome aberrations, was approximately doubled after one month of work; it further increased after two months of work; remained in this range up to seven months of exposure; and then tended to decrease somewhat. Blood lead levels increased progressively in the first few months, then reached a steady state. Urinary lead and coproporphyrin levels increased sharply after one month of work, while urinary delta-aminolevulinic acid (ALA) levels increased moderately. The ALA dehydratase (ALAD) activity of red blood cells (RBCs) was reduced to almost 50% of the initial values after one month, decreased further in subsequent months, and remained decreased through the remainder of the study.", "contents": "Initial occupational exposure to lead: Chromosome and Biochemical findings. Serial chromosome and biochemical studies were carried out in 11 subjects before and during initial occupational exposure to moderate quantities of lead fumes in a storage battery plant. The rate of abnormal metaphases, mostly with chromatid and one-break chromosome aberrations, was approximately doubled after one month of work; it further increased after two months of work; remained in this range up to seven months of exposure; and then tended to decrease somewhat. Blood lead levels increased progressively in the first few months, then reached a steady state. Urinary lead and coproporphyrin levels increased sharply after one month of work, while urinary delta-aminolevulinic acid (ALA) levels increased moderately. The ALA dehydratase (ALAD) activity of red blood cells (RBCs) was reduced to almost 50% of the initial values after one month, decreased further in subsequent months, and remained decreased through the remainder of the study."} {"id": "PMID:1259478", "title": "Studies of plasma renin activity in coarctation of the aorta.", "content": "Experimental and clinical studies were performed to assess the role of the renin-angiotensin system in producing hypertension in coarctation of the aorta. Basal and stimulated peripheral plasma renin activity were determined in the canine model and in four patients with coarctation. The animal studies showed no significant elevation of peripheral plasma renin activity (PPRA), and no increase in the response of PPRA to stimuli. The human studies showed a significant elevation in the response to PPRA to postural change and to exercise in three of four patients with coarctation, as compared to the same patients after correction of the coarctation. It is concluded that hyperactivity of the renin-angiotensin system is not the primary cause in coarctation hypertension in dog or man. It is nonetheless probable that the renin-angiotensin system has a role in coarctation hypertension, and further studies will be necessary to determine its place.", "contents": "Studies of plasma renin activity in coarctation of the aorta. Experimental and clinical studies were performed to assess the role of the renin-angiotensin system in producing hypertension in coarctation of the aorta. Basal and stimulated peripheral plasma renin activity were determined in the canine model and in four patients with coarctation. The animal studies showed no significant elevation of peripheral plasma renin activity (PPRA), and no increase in the response of PPRA to stimuli. The human studies showed a significant elevation in the response to PPRA to postural change and to exercise in three of four patients with coarctation, as compared to the same patients after correction of the coarctation. It is concluded that hyperactivity of the renin-angiotensin system is not the primary cause in coarctation hypertension in dog or man. It is nonetheless probable that the renin-angiotensin system has a role in coarctation hypertension, and further studies will be necessary to determine its place."} {"id": "PMID:1259479", "title": "Major hepatic vein ligation necessitated by blunt abdominal trauma.", "content": "An unusual case involving avulsion of the middle and left hepatic veins secondary to blunt trauma is presented. Operative management of the injury resulted in ligation of both veins without resection of the parenchyma acutely deprived of venous outflow. The postoperative evaluation and review of the literature indicate that liver tissue will survive acute interruption of a major portion of its venous outflow. This case demonstrates that if after ligating major hepatic vein, the condition of the obstructed parenchyma stabilizes or improves under direct observation and if the condition of the patient does not deteriorate, resection may not be required.", "contents": "Major hepatic vein ligation necessitated by blunt abdominal trauma. An unusual case involving avulsion of the middle and left hepatic veins secondary to blunt trauma is presented. Operative management of the injury resulted in ligation of both veins without resection of the parenchyma acutely deprived of venous outflow. The postoperative evaluation and review of the literature indicate that liver tissue will survive acute interruption of a major portion of its venous outflow. This case demonstrates that if after ligating major hepatic vein, the condition of the obstructed parenchyma stabilizes or improves under direct observation and if the condition of the patient does not deteriorate, resection may not be required."} {"id": "PMID:1259474", "title": "Aerosol usage and respiratory symptoms.", "content": "In an epidemiological study of 3,485 selected individuals in Tucson, aerosol usage appears to be correlated to prevalence of respiratory symptoms. This effect persists after adjusting age and smoking to the prevalence rates for symptoms and appears to exist for specific types of aerosols. Further specification and clarification of these relationships are needed in the epidemiological survey. Critical evaluation within in vitro and in vivo models is of great importance. It is concluded that the propellants, the ingredients of the application, and the combination elements in different circumstances must be studied toxicologically to determine the mechanism and extent of specific actions on organisms.", "contents": "Aerosol usage and respiratory symptoms. In an epidemiological study of 3,485 selected individuals in Tucson, aerosol usage appears to be correlated to prevalence of respiratory symptoms. This effect persists after adjusting age and smoking to the prevalence rates for symptoms and appears to exist for specific types of aerosols. Further specification and clarification of these relationships are needed in the epidemiological survey. Critical evaluation within in vitro and in vivo models is of great importance. It is concluded that the propellants, the ingredients of the application, and the combination elements in different circumstances must be studied toxicologically to determine the mechanism and extent of specific actions on organisms."} {"id": "PMID:1259476", "title": "Effect of chromates on ciliated cells of rat tracheal epithelium.", "content": "Exposure to chromates is an occupational hazard that may result in disease of the respiratory tract. Specific subcellular effects of exposure to this chemical that might be the basis for observed pathologic findings were assessed in tracheal organ culture and excised whole tracheas. Chromate concentrations of 10 mg/ml or more were found to induce ciliostasis within 20 minutes and to kill cells within 24 hours. Levels between 10mug/ml and 100 mug/ml were not ciliostatic but resulted in cytotoxicity after a delay of several hours. Ultrastructural alterations associated with chromate-induced cytotoxicity are similar to the progressive degenerative changes that result from other chemical injuries. An inhibitory effect of chromate on protein synthesis, RNA synthesis, or succinic dehydrogenase activity could not be demonstrated. The data suggest that damage to the plasmalemma by chromates may be responsible for the observed change.", "contents": "Effect of chromates on ciliated cells of rat tracheal epithelium. Exposure to chromates is an occupational hazard that may result in disease of the respiratory tract. Specific subcellular effects of exposure to this chemical that might be the basis for observed pathologic findings were assessed in tracheal organ culture and excised whole tracheas. Chromate concentrations of 10 mg/ml or more were found to induce ciliostasis within 20 minutes and to kill cells within 24 hours. Levels between 10mug/ml and 100 mug/ml were not ciliostatic but resulted in cytotoxicity after a delay of several hours. Ultrastructural alterations associated with chromate-induced cytotoxicity are similar to the progressive degenerative changes that result from other chemical injuries. An inhibitory effect of chromate on protein synthesis, RNA synthesis, or succinic dehydrogenase activity could not be demonstrated. The data suggest that damage to the plasmalemma by chromates may be responsible for the observed change."} {"id": "PMID:1259475", "title": "Mood and lithium in drinking water.", "content": "To assess the possible relationship of lithium in the drinking water to some aspects of mental health, drinking water samples were collected from the homes of 384 individuals in Washington County, Md, who had been randomly selected for interview in a community mental health assessment program. The water was analyzed for lithium by atomic absorption spectrophotometry without knowledge of the interview results. The questionnaire contained the Lubin depression adjective check list, Center for Epidemiologic Studies depression and functioning scales, a general happiness question (Gurin), an aggression scale, and the Cantril ladder for self-rating of present status. In an area with low-to-moderate levels of lithium in the drinking water, there was no evidence to confirm earlier suggestions that the presence of lithium might be beneficial.", "contents": "Mood and lithium in drinking water. To assess the possible relationship of lithium in the drinking water to some aspects of mental health, drinking water samples were collected from the homes of 384 individuals in Washington County, Md, who had been randomly selected for interview in a community mental health assessment program. The water was analyzed for lithium by atomic absorption spectrophotometry without knowledge of the interview results. The questionnaire contained the Lubin depression adjective check list, Center for Epidemiologic Studies depression and functioning scales, a general happiness question (Gurin), an aggression scale, and the Cantril ladder for self-rating of present status. In an area with low-to-moderate levels of lithium in the drinking water, there was no evidence to confirm earlier suggestions that the presence of lithium might be beneficial."} {"id": "PMID:1259480", "title": "Parasympathetic innervation and pancreatic secretion: the role of the gastric antrum.", "content": "The role of the antrum on vagally mediated pancreatic secretion was studied in 8 conscious dogs prepared with chronic pancreatic and gastric fistulae. After completion of control studies 6 were subjected to antrectomy and 2 to antroneurolysis (to interrupt submucosal nerve connections); secretory studies were repeated. With the animals secreting in response to secretin(0.03 u per kg-min) or secretin with cholecystokinin (0.05 u per kg-min), the following were administered: 1) insulin 0.2 u/kg; 2) atropine 0.2 and 0.4 mg/kg; 3) insulin after atropine. Insulin hypoglycemia elicited a marked enzyme response. Both antrectomy and antroneurolysis markedly reduced (80%) the enzyme response to insulin hypoglycemia. Atropine 0.2 mg/kg abolished the insulin response and at 0.4 mg/kg inhibited (50%) the enzyme response to cholecystokinin; these effects were unaltered by antrectomy or antroneurolysis. These experiments suggest that the pancreatic enzyme response to insulin hypoglycemia is predominantly mediated through the vagal release of antral gastrin. Furthermore, antrectomy and antroneurolysis do not affect the enzyme response to cholecystokinin nor do they alter the inhibitory effects of atropine. The inhibitio- by atropine suggests that a cholinergic background exerts a permissive effect on CCK-mediated enzyme secretion.", "contents": "Parasympathetic innervation and pancreatic secretion: the role of the gastric antrum. The role of the antrum on vagally mediated pancreatic secretion was studied in 8 conscious dogs prepared with chronic pancreatic and gastric fistulae. After completion of control studies 6 were subjected to antrectomy and 2 to antroneurolysis (to interrupt submucosal nerve connections); secretory studies were repeated. With the animals secreting in response to secretin(0.03 u per kg-min) or secretin with cholecystokinin (0.05 u per kg-min), the following were administered: 1) insulin 0.2 u/kg; 2) atropine 0.2 and 0.4 mg/kg; 3) insulin after atropine. Insulin hypoglycemia elicited a marked enzyme response. Both antrectomy and antroneurolysis markedly reduced (80%) the enzyme response to insulin hypoglycemia. Atropine 0.2 mg/kg abolished the insulin response and at 0.4 mg/kg inhibited (50%) the enzyme response to cholecystokinin; these effects were unaltered by antrectomy or antroneurolysis. These experiments suggest that the pancreatic enzyme response to insulin hypoglycemia is predominantly mediated through the vagal release of antral gastrin. Furthermore, antrectomy and antroneurolysis do not affect the enzyme response to cholecystokinin nor do they alter the inhibitory effects of atropine. The inhibitio- by atropine suggests that a cholinergic background exerts a permissive effect on CCK-mediated enzyme secretion."} {"id": "PMID:1259481", "title": "Studies on the effect of small bowel bypass for massive obesity on gastric secretory function.", "content": "Gastric secretory function was studied in 20 morbidly obese patients both before and after jejuno-ileal bypass. The mean postoperative weight loss was 99.2 pounds during a mean postoperative followup period of 12.6 months. The gastric secretory values we studied included basal and histalogstimulated volume, pH, concentration, and output. No statistically significant changes were observed in any of these variables. Therefore it is suggested that jejuno-ileal bypass, as performed for morbid obesity, is probably not an ulcerogenic procedure.", "contents": "Studies on the effect of small bowel bypass for massive obesity on gastric secretory function. Gastric secretory function was studied in 20 morbidly obese patients both before and after jejuno-ileal bypass. The mean postoperative weight loss was 99.2 pounds during a mean postoperative followup period of 12.6 months. The gastric secretory values we studied included basal and histalogstimulated volume, pH, concentration, and output. No statistically significant changes were observed in any of these variables. Therefore it is suggested that jejuno-ileal bypass, as performed for morbid obesity, is probably not an ulcerogenic procedure."} {"id": "PMID:1259482", "title": "Treatment of volvulus of the colon by colonoscopy.", "content": "The flexible colonoscope has notable advantages over rigid instruments and can be offered as an alternative and (probably) preferable method for non-surgical reduction of colonic volvulus. When operative intervention is called for because of repeated bouts of sigmoid volvulus, colonoscopy offers a means of preoperative deflation of the twisted loop, allowing time to prepare the bowel and correct systemic disturbances such as electrolyte imbalance. The first successful management of a case of recurrent sigmoid volvulus using fiberoptic flexible colonoscope is presented. It is suggested that the fiberoptic colonoscope may have similar application for instances of volvulus occurring more proximal than in the sigmoid colon. Sigmoid volvulus in children even though rare might also be amenable to correction by colonoscopy.", "contents": "Treatment of volvulus of the colon by colonoscopy. The flexible colonoscope has notable advantages over rigid instruments and can be offered as an alternative and (probably) preferable method for non-surgical reduction of colonic volvulus. When operative intervention is called for because of repeated bouts of sigmoid volvulus, colonoscopy offers a means of preoperative deflation of the twisted loop, allowing time to prepare the bowel and correct systemic disturbances such as electrolyte imbalance. The first successful management of a case of recurrent sigmoid volvulus using fiberoptic flexible colonoscope is presented. It is suggested that the fiberoptic colonoscope may have similar application for instances of volvulus occurring more proximal than in the sigmoid colon. Sigmoid volvulus in children even though rare might also be amenable to correction by colonoscopy."} {"id": "PMID:1259483", "title": "The anatomic basis of parathyroid surgery.", "content": "A study of 645 normal adult parathyroid glands in 160 cadavers revealed that there is a definite pattern of anatomic distribution on the basis of the embryologic development of the parathyroid, thyroid, and thymic glands. The sites of predilection of the upper gland (Parathyroid IV) are, in order of frequency, the cricothyroid junction; the dorsum of the upper pole of the thyroid; and the retropharyngeal space. Those of the lower gland (Parathyroid III) are at the lower pole of the thyroid and the thymic tongue; rarely in the upper, the lateral neck, or the mediastinum. An understanding of the developmental relationship of the parathyroid glands to the thyroid and the thymus is fundamental in the delineation of the embryologic origin of the parathyroid glands. The parathyroid gland, located within the surgical capsule of the thyroid (subcapsular), when diseased, remains in place locally. A gland outside of the capsule (extracapsular) is often displaced into the posterior or anterior mediastinum. A collective assessment of the size, weight, color, shape, and consistency of the parathyroid gland is mandatory in the determination of its normalcy. Frozen section examination for stromal and intracellular fatty content is an added assurance of normalcy. That parathyroid glands sink in saline solution, and fat globules float, may aid in differentiating the two types of tissue. Supernumerary, fused, and intrathyroidal parathyroids, albeit rare, are of surgical importance.", "contents": "The anatomic basis of parathyroid surgery. A study of 645 normal adult parathyroid glands in 160 cadavers revealed that there is a definite pattern of anatomic distribution on the basis of the embryologic development of the parathyroid, thyroid, and thymic glands. The sites of predilection of the upper gland (Parathyroid IV) are, in order of frequency, the cricothyroid junction; the dorsum of the upper pole of the thyroid; and the retropharyngeal space. Those of the lower gland (Parathyroid III) are at the lower pole of the thyroid and the thymic tongue; rarely in the upper, the lateral neck, or the mediastinum. An understanding of the developmental relationship of the parathyroid glands to the thyroid and the thymus is fundamental in the delineation of the embryologic origin of the parathyroid glands. The parathyroid gland, located within the surgical capsule of the thyroid (subcapsular), when diseased, remains in place locally. A gland outside of the capsule (extracapsular) is often displaced into the posterior or anterior mediastinum. A collective assessment of the size, weight, color, shape, and consistency of the parathyroid gland is mandatory in the determination of its normalcy. Frozen section examination for stromal and intracellular fatty content is an added assurance of normalcy. That parathyroid glands sink in saline solution, and fat globules float, may aid in differentiating the two types of tissue. Supernumerary, fused, and intrathyroidal parathyroids, albeit rare, are of surgical importance."} {"id": "PMID:1259485", "title": "Distribution of myocardial blood flow measured by hydrogen polarography.", "content": "Distribution of myocardial blood flow was studied by polarographic recording of hydrogen desaturation in open chest dogs. Flow was measured during normal cardiac activity, reactive hyperemia following 60 seconds of coronary artery occlusion, and left ventricular hypertension produced by either partial supravalvular aortic occlusion or subvalvular outflow constriction. During normal cardiac function, blood flows in the subepicardium and subendocardium were approximately equal. Reactive hyperemia increased flow to both the subepicardium and subendocardium. Left ventricular hypertension decreased subendocardial flow relative to subepicardial flow in proportion to the degree of hypertension. Marked supravalvular obstruction with ventricular hypertension reduced subendocardial flow to two-thirds that of subepicardial flow. This decrease was further accentuated when the left ventricular end diastolic pressure was elevated.", "contents": "Distribution of myocardial blood flow measured by hydrogen polarography. Distribution of myocardial blood flow was studied by polarographic recording of hydrogen desaturation in open chest dogs. Flow was measured during normal cardiac activity, reactive hyperemia following 60 seconds of coronary artery occlusion, and left ventricular hypertension produced by either partial supravalvular aortic occlusion or subvalvular outflow constriction. During normal cardiac function, blood flows in the subepicardium and subendocardium were approximately equal. Reactive hyperemia increased flow to both the subepicardium and subendocardium. Left ventricular hypertension decreased subendocardial flow relative to subepicardial flow in proportion to the degree of hypertension. Marked supravalvular obstruction with ventricular hypertension reduced subendocardial flow to two-thirds that of subepicardial flow. This decrease was further accentuated when the left ventricular end diastolic pressure was elevated."} {"id": "PMID:1259486", "title": "Acute anuria secondary to renal artery stenosis.", "content": "Three patients with acute onset of anuria secondary to renal malperfusion were successfully treated by revascularization. Twelve such patients have previously been reported. The role of surgery for prophylaxis in stenosing renal artery disease is advocated.", "contents": "Acute anuria secondary to renal artery stenosis. Three patients with acute onset of anuria secondary to renal malperfusion were successfully treated by revascularization. Twelve such patients have previously been reported. The role of surgery for prophylaxis in stenosing renal artery disease is advocated."} {"id": "PMID:1259487", "title": "Ascending vs descending aortic dissections.", "content": "One hundred eight patients with spontaneously developing thoracic aortic dissection were seen between 1966-1973, 78 of whom had acute dissection and 30 chronic. The age (49 vs 60 yrs) and incidence of hypertension (32% vs 71%) were significantly lower in the 56 patients in whom dissection originated in ascending aorta than in the 52 patients in whom the dissection originated in the upper descending aorta. The mortality rate in medically treated patients with acute ascending aortic dissection was 88%. Cardiac tamponade was the major cause of death. The mortality rate was significantly lower in those who were treated surgically (24%). Fifteen (54%) of the patients with ascending aortic dissection and significant aortic incompetence did not have aortic valve replacement and only two subsequently (53 and 92 months later) required valve replacement. Although the initial mortality in patients with acute descending aortic dissection treated medically and surgically was similar, the long term survival rate was higher in the surgically treated group. We conclude that ascending aortic dissection and descending aortic dissection have different clinical profiles and prognoses. Immediate surgical intervention is indicated in patients with acute ascending aortic dissection. Patients with acute descending aortic dissection can be treated medically initially followed by early elective operation.", "contents": "Ascending vs descending aortic dissections. One hundred eight patients with spontaneously developing thoracic aortic dissection were seen between 1966-1973, 78 of whom had acute dissection and 30 chronic. The age (49 vs 60 yrs) and incidence of hypertension (32% vs 71%) were significantly lower in the 56 patients in whom dissection originated in ascending aorta than in the 52 patients in whom the dissection originated in the upper descending aorta. The mortality rate in medically treated patients with acute ascending aortic dissection was 88%. Cardiac tamponade was the major cause of death. The mortality rate was significantly lower in those who were treated surgically (24%). Fifteen (54%) of the patients with ascending aortic dissection and significant aortic incompetence did not have aortic valve replacement and only two subsequently (53 and 92 months later) required valve replacement. Although the initial mortality in patients with acute descending aortic dissection treated medically and surgically was similar, the long term survival rate was higher in the surgically treated group. We conclude that ascending aortic dissection and descending aortic dissection have different clinical profiles and prognoses. Immediate surgical intervention is indicated in patients with acute ascending aortic dissection. Patients with acute descending aortic dissection can be treated medically initially followed by early elective operation."} {"id": "PMID:1259488", "title": "Insulin response to glucose in hypermetabolic burn patients.", "content": "Fifty-four intravenous glucose tolerance tests were performed in 12 normal individuals and 21 thermally injured patients. In the 17 hypermetabolic burn patients studied between the 6th and 16th days postinjury, fasting blood glucose was elevated (111 +/- 7 mg/100 ml, mean +/- SE compared to 85 +/- 3 in controls, P less than 0.001), but the instantaneous proportionality constant for glucose disappearance (k) was similar to that obtained in normal individuals (5.27 +/- 0.51, 100/min vs 4.01 +/- 0.58 in normals, NS). Fasting serum insulin concentrations were comparable in the 12 normals and 17 hypermetabolic burn patients (22 +/- 3muU/ml in normals vs 22 +/- 2), as was fasting insulin corrected for fasting glucose (24 +/- 3 in normals vs 21 +/- 3, NS), initial insulin response (0-10 min delta insulin, 58 +/- 13 in normals vs 67 +/- 10, NS) or total insulin response corrected per unit glycemic stimulus (insulinogenic index, 0.48 +/- 0.10 in normals vs 0.52 +/- 0.07, NS). With time following injury, the proportionality constant for glucose disappearance and insulin response decreased, and these alterations were related to the posttraumatic weight loss. In the 5 convalescent patients studied between the 37th and 90th days postinjury, glucose and insulin dynamics appeared similar to those observed in starved man. In these burn patients, hypermetabolism and negative nitrogen balance occurred in association with a normal insulin response to glucose. Increased hepatic gluconeogenesis appears to be characteristic of the catabolic response to this stress, directed by increased glucagon and catecholamines, not a decrease in fasting insulin or dampened insulin response.", "contents": "Insulin response to glucose in hypermetabolic burn patients. Fifty-four intravenous glucose tolerance tests were performed in 12 normal individuals and 21 thermally injured patients. In the 17 hypermetabolic burn patients studied between the 6th and 16th days postinjury, fasting blood glucose was elevated (111 +/- 7 mg/100 ml, mean +/- SE compared to 85 +/- 3 in controls, P less than 0.001), but the instantaneous proportionality constant for glucose disappearance (k) was similar to that obtained in normal individuals (5.27 +/- 0.51, 100/min vs 4.01 +/- 0.58 in normals, NS). Fasting serum insulin concentrations were comparable in the 12 normals and 17 hypermetabolic burn patients (22 +/- 3muU/ml in normals vs 22 +/- 2), as was fasting insulin corrected for fasting glucose (24 +/- 3 in normals vs 21 +/- 3, NS), initial insulin response (0-10 min delta insulin, 58 +/- 13 in normals vs 67 +/- 10, NS) or total insulin response corrected per unit glycemic stimulus (insulinogenic index, 0.48 +/- 0.10 in normals vs 0.52 +/- 0.07, NS). With time following injury, the proportionality constant for glucose disappearance and insulin response decreased, and these alterations were related to the posttraumatic weight loss. In the 5 convalescent patients studied between the 37th and 90th days postinjury, glucose and insulin dynamics appeared similar to those observed in starved man. In these burn patients, hypermetabolism and negative nitrogen balance occurred in association with a normal insulin response to glucose. Increased hepatic gluconeogenesis appears to be characteristic of the catabolic response to this stress, directed by increased glucagon and catecholamines, not a decrease in fasting insulin or dampened insulin response."} {"id": "PMID:1259489", "title": "High-output congestive failure from femoral arteriovenous shunts for vascular access.", "content": "Femoral arteriovenous bovine shunts (FAVBS) represent an accepted method of vascular access for patients requiring chronic hemodialysis. The authors present 4 patients who required corrective surgery for high-putput congestive heart failure (HOCHF) secondary to high flow rates through the shunt. In order to avoid this serious complication, intraoperative graft flow rates should not exceed 900 cc/min. HOCHF secondary to FAVBS may be refractory to conservative therapy and require either banding of the shunt or its removal.", "contents": "High-output congestive failure from femoral arteriovenous shunts for vascular access. Femoral arteriovenous bovine shunts (FAVBS) represent an accepted method of vascular access for patients requiring chronic hemodialysis. The authors present 4 patients who required corrective surgery for high-putput congestive heart failure (HOCHF) secondary to high flow rates through the shunt. In order to avoid this serious complication, intraoperative graft flow rates should not exceed 900 cc/min. HOCHF secondary to FAVBS may be refractory to conservative therapy and require either banding of the shunt or its removal."} {"id": "PMID:1259490", "title": "Use of a left heart assist device after intracardiac surgery: technique and clinical experience.", "content": "A left heart assist device (LHAD) has been employed in 14 patients. All had advanced heart disease and were in low cardiac output after repair, such that they could not be separated from cardiopulmonary bypass despite prolonged support and adjuvant therapy, including drugs, pacing, and use of intraaortic balloon counterpulsation whenever possible. Apart from special cannulas, the equipment necessary for the LHAD is widely available. An asset of the system (left atrial-ascending aorta bypass of the left ventricle) is that it may be terminated without reentering the thorax to remove the cannulas. This is accomplished with precisely fitting obturators that obliterate the cannula lumens and allow the tubes to be permanently implanted. This concept is believed important since critically ill patients requiring support are precisely those in whom added risk would be imposed by a second operation. Of the 14 patients who have had intraoperative and postoperative support (up to 6.8 days), 9 were weaned from the device and 6 were dismissed from the hospital. Four patients remain alive and are improved, the longest at 22 months since operation. The favorable performance of the LHAD suggests that it may prove useful either when intraaortic balloon counterpulsation cannot be successfully deployed or when it has failed to achieve hemodynamic stability.", "contents": "Use of a left heart assist device after intracardiac surgery: technique and clinical experience. A left heart assist device (LHAD) has been employed in 14 patients. All had advanced heart disease and were in low cardiac output after repair, such that they could not be separated from cardiopulmonary bypass despite prolonged support and adjuvant therapy, including drugs, pacing, and use of intraaortic balloon counterpulsation whenever possible. Apart from special cannulas, the equipment necessary for the LHAD is widely available. An asset of the system (left atrial-ascending aorta bypass of the left ventricle) is that it may be terminated without reentering the thorax to remove the cannulas. This is accomplished with precisely fitting obturators that obliterate the cannula lumens and allow the tubes to be permanently implanted. This concept is believed important since critically ill patients requiring support are precisely those in whom added risk would be imposed by a second operation. Of the 14 patients who have had intraoperative and postoperative support (up to 6.8 days), 9 were weaned from the device and 6 were dismissed from the hospital. Four patients remain alive and are improved, the longest at 22 months since operation. The favorable performance of the LHAD suggests that it may prove useful either when intraaortic balloon counterpulsation cannot be successfully deployed or when it has failed to achieve hemodynamic stability."} {"id": "PMID:1259491", "title": "An extravascular left ventricular assist device.", "content": "The hemodynamic efficacy and prosthesis-vessel interaction of a pneumatically activated circulatory assist device was investigated in 12 acute and 12 chronic studies in dogs. A polyurethane balloon encased in Dacron-velour cloth was fastened to the descending thoracic aorta with a spiral wrapping of Dacron graft material. Diastolic augmentation was provided by rhythmic inflation and deflation of the balloon. Hemodynamic results, based on 5 dogs with experimental myocardial ischemia, showed that left ventricular systolic peak pressure decreased by 8.2 +/- 1.9%, cardiac output increased by 13.1 +/- 2.8%, and circumflex coronary artery flow rose by 17.5 +/- 2.5%. In the chronic experiments the prosthesis was asynchronously but continuously activated from one to sixteen weeks at 74 cycles per minute. Postmortem examination of the implantation site in all 12 dogs showed that necrosis had developed but was limited to the outer half of the medial layer beneath the pumping chamber and that the aortic wall was compressed to about 70% of its original thickness. Although the method described represents a simple form of providing ventricular assistance, its applicability for long-term circulatory support remains to be evaluated.", "contents": "An extravascular left ventricular assist device. The hemodynamic efficacy and prosthesis-vessel interaction of a pneumatically activated circulatory assist device was investigated in 12 acute and 12 chronic studies in dogs. A polyurethane balloon encased in Dacron-velour cloth was fastened to the descending thoracic aorta with a spiral wrapping of Dacron graft material. Diastolic augmentation was provided by rhythmic inflation and deflation of the balloon. Hemodynamic results, based on 5 dogs with experimental myocardial ischemia, showed that left ventricular systolic peak pressure decreased by 8.2 +/- 1.9%, cardiac output increased by 13.1 +/- 2.8%, and circumflex coronary artery flow rose by 17.5 +/- 2.5%. In the chronic experiments the prosthesis was asynchronously but continuously activated from one to sixteen weeks at 74 cycles per minute. Postmortem examination of the implantation site in all 12 dogs showed that necrosis had developed but was limited to the outer half of the medial layer beneath the pumping chamber and that the aortic wall was compressed to about 70% of its original thickness. Although the method described represents a simple form of providing ventricular assistance, its applicability for long-term circulatory support remains to be evaluated."} {"id": "PMID:1259492", "title": "Production of controlled reversible left ventricular failure in calves using intracoronary lidocaine hydrochloride: a useful method of evaluating left ventricular assist devices.", "content": "The experimental production of stable, controlled, short-term left ventricular failure is valuable in the evaluation of implantable circulatory support systems. Acute or chronic left ventricular failure produced by occlusion or embolization of coronary arteries results in muscle dysfunction and degrees of failure that may be difficult to control. The effects of varying amounts of intracoronary lidocaine were studied during short- and long-term evaluations of intracorporeal left ventricular assist pumping. In 8 Hereford calves the left main coronary artery was cannulated with an intracoronary catheter in open and closed chest preparations. Dose-related negative inotropic effects were noted when lidocaine was injected at individual doses of 50, 75, and 100 mg. Following 100 mg doses, mean aortic pressure, cardiac output, and maximum rate of rise of left ventricular pressure decreased; left ventricular end-diastolic pressure increased fourfold. Similar effects were noted with short continuous infusions of lidocaine. The initial responses to injection or continuous infusions, if effective, were noted within 40 to 60 seconds. Several episodes of failure could be produced with either method following recovery periods of 10 to 15 minutes. In all instances, actuation of a left ventricular assist device immediately reversed the hemodynamic effects of the pharmacologically induced failure.", "contents": "Production of controlled reversible left ventricular failure in calves using intracoronary lidocaine hydrochloride: a useful method of evaluating left ventricular assist devices. The experimental production of stable, controlled, short-term left ventricular failure is valuable in the evaluation of implantable circulatory support systems. Acute or chronic left ventricular failure produced by occlusion or embolization of coronary arteries results in muscle dysfunction and degrees of failure that may be difficult to control. The effects of varying amounts of intracoronary lidocaine were studied during short- and long-term evaluations of intracorporeal left ventricular assist pumping. In 8 Hereford calves the left main coronary artery was cannulated with an intracoronary catheter in open and closed chest preparations. Dose-related negative inotropic effects were noted when lidocaine was injected at individual doses of 50, 75, and 100 mg. Following 100 mg doses, mean aortic pressure, cardiac output, and maximum rate of rise of left ventricular pressure decreased; left ventricular end-diastolic pressure increased fourfold. Similar effects were noted with short continuous infusions of lidocaine. The initial responses to injection or continuous infusions, if effective, were noted within 40 to 60 seconds. Several episodes of failure could be produced with either method following recovery periods of 10 to 15 minutes. In all instances, actuation of a left ventricular assist device immediately reversed the hemodynamic effects of the pharmacologically induced failure."} {"id": "PMID:1259493", "title": "Factors predictive of perioperative myocardial infarction during coronary operations.", "content": "The diagnosis of perioperative myocardial infarction (PMI) in our patients was based upon electrocardiography, vectorcardiography, and postoperative enzyme changes. A group of 303 patients operated on between January and September, 1972, formed the basis of this study. Three groups were identified from among these patients. Group A was composed of 90 consecutive patients in whom MI was excluded by all criteria. Group B comprised 25 patients with proved MI and yielded the 8% incidence of MI among our patients. Group C included 34 patients with triple-vessel disease who did not sustain MI. Significantly more patients sustaining MI had preinfarction angina and severe coronary artery disease. The incidence of MI was also higher in patients with diffuse disease and those in whom the lesions could not be totally bypassed. A statistical correlation with longer pump runs and periods of anoxia was obtained. There was some suggestion that the preoperative location of the hypokinetic segment determined the site of MI in patients.", "contents": "Factors predictive of perioperative myocardial infarction during coronary operations. The diagnosis of perioperative myocardial infarction (PMI) in our patients was based upon electrocardiography, vectorcardiography, and postoperative enzyme changes. A group of 303 patients operated on between January and September, 1972, formed the basis of this study. Three groups were identified from among these patients. Group A was composed of 90 consecutive patients in whom MI was excluded by all criteria. Group B comprised 25 patients with proved MI and yielded the 8% incidence of MI among our patients. Group C included 34 patients with triple-vessel disease who did not sustain MI. Significantly more patients sustaining MI had preinfarction angina and severe coronary artery disease. The incidence of MI was also higher in patients with diffuse disease and those in whom the lesions could not be totally bypassed. A statistical correlation with longer pump runs and periods of anoxia was obtained. There was some suggestion that the preoperative location of the hypokinetic segment determined the site of MI in patients."} {"id": "PMID:1259494", "title": "A new approach to repair of pulmonary branch stenosis following ascending aorta-right pulmonary artery anastomosis.", "content": "Ascending aorta-right pulmonary artery anastomosis may result in branch stenosis or occlusion of the right pulmonary artery from growth or from failure to place the anastomosis on the posterior surface of the aorta at the time of construction. Closure of the anastomosis is usually easily accomplished by simple suture through the ascending aorta. When branch stenosis is present at the site of anastomosis, reconstruction of the pulmonary artery is necessary. A new approach that facilitates repair of pulmonary branch stenosis by transecting the ascending aorta over the obstructed area has been utilized in 2 patients who required reoperation for branch stenosis following repair for tetralogy of Fallot. The method is an alternative approach to gain exposure for reconstruction of the pulmonary artery.", "contents": "A new approach to repair of pulmonary branch stenosis following ascending aorta-right pulmonary artery anastomosis. Ascending aorta-right pulmonary artery anastomosis may result in branch stenosis or occlusion of the right pulmonary artery from growth or from failure to place the anastomosis on the posterior surface of the aorta at the time of construction. Closure of the anastomosis is usually easily accomplished by simple suture through the ascending aorta. When branch stenosis is present at the site of anastomosis, reconstruction of the pulmonary artery is necessary. A new approach that facilitates repair of pulmonary branch stenosis by transecting the ascending aorta over the obstructed area has been utilized in 2 patients who required reoperation for branch stenosis following repair for tetralogy of Fallot. The method is an alternative approach to gain exposure for reconstruction of the pulmonary artery."} {"id": "PMID:1259498", "title": "Skid row alcoholism. A distinct sociomedical entity.", "content": "The physical-disease charcteristics of 125 skid row and 736 non-skid row male alcoholics were compared in detail to determine whether skid row alcoholism is characterized by a distinct medical, as well as a social, profile. Trauma, tuberculosis, venereal disease, and malnutrition were more common in the skid row alcoholics. Epilepsy, peripheral neuritis, acute brain syndromes, chronic brain disease, and lifetime recordings of all nervous system illnesses also occurred more frequently in the skid row group, as did gastritis, gastrointestinal hemorrhage, ulcer surgery, and postgastrectomy syndrome. Fatty liver, hypertension, ischemic heart disease, cardiomyopathy, and cardiovascular illnesses of all kinds, however, were less common. The skid row medical profile is, in part, the product of a unique sociologic environment. Thus, skid row alcoholism may be viewed as a distinct sociomedical entity.", "contents": "Skid row alcoholism. A distinct sociomedical entity. The physical-disease charcteristics of 125 skid row and 736 non-skid row male alcoholics were compared in detail to determine whether skid row alcoholism is characterized by a distinct medical, as well as a social, profile. Trauma, tuberculosis, venereal disease, and malnutrition were more common in the skid row alcoholics. Epilepsy, peripheral neuritis, acute brain syndromes, chronic brain disease, and lifetime recordings of all nervous system illnesses also occurred more frequently in the skid row group, as did gastritis, gastrointestinal hemorrhage, ulcer surgery, and postgastrectomy syndrome. Fatty liver, hypertension, ischemic heart disease, cardiomyopathy, and cardiovascular illnesses of all kinds, however, were less common. The skid row medical profile is, in part, the product of a unique sociologic environment. Thus, skid row alcoholism may be viewed as a distinct sociomedical entity."} {"id": "PMID:1259499", "title": "Cardiac failure and upper extremity arteriovenous dialysis fistulas. Case reports and a review of the literature.", "content": "Nine patients with high-output cardiac failure from arteriovenous forearm dialysis fistulas are reviewed, and six new cases are presented. Decreases in cardiac output with temporary fistula occlusion ranged from 0.3 to 11.0 liters/min (mean, 2.9 liters/min); fistula flow rates varied from 0.6 to 2.9 liter/min (mean, 1.5 liters/min). Surgical correction of high-flow fistulas resulted in notable improvement of cardiac failure in 13 of 14 patients. Although cardiac failure in individuals who are receiving long-term dialysis treatment is usually caused by intrinsic cardiac disease, volume overload, or anemia, forearm fistulas with large flow rates may be an important contributing factor. Correction of these large flow rates may be an important contributing factor. Correction of these large flow rates by banding or closure can substantially improve cardiac function in selected patients.", "contents": "Cardiac failure and upper extremity arteriovenous dialysis fistulas. Case reports and a review of the literature. Nine patients with high-output cardiac failure from arteriovenous forearm dialysis fistulas are reviewed, and six new cases are presented. Decreases in cardiac output with temporary fistula occlusion ranged from 0.3 to 11.0 liters/min (mean, 2.9 liters/min); fistula flow rates varied from 0.6 to 2.9 liter/min (mean, 1.5 liters/min). Surgical correction of high-flow fistulas resulted in notable improvement of cardiac failure in 13 of 14 patients. Although cardiac failure in individuals who are receiving long-term dialysis treatment is usually caused by intrinsic cardiac disease, volume overload, or anemia, forearm fistulas with large flow rates may be an important contributing factor. Correction of these large flow rates may be an important contributing factor. Correction of these large flow rates by banding or closure can substantially improve cardiac function in selected patients."} {"id": "PMID:1259500", "title": "Spectrum of pleural involvement in sarcoidosis.", "content": "Pleural involvement has generally been considered an unusual aspect of sarcoidosis. In this paper, five previously unreported cases of sarcoidosis involving the pleura were discussed. Pleural sarcoidosis may be manifested by the presence of a pleural effusion, and the diagnosis is based on the exclusion of all other possible causes and the demonstration of noncaseating granulomas in the pleura. When the pleura is involved without effusion, it may only be recognized if noncaseating granulomas involving the pleura are looked for specifically. Including the five cases form this study, there have been 73 cases of pleural sarcoidosis reported, but only 37 have been verified by histologic evidence. When strict diagnostic criteria are used, clinical involvement of the pleura in sarsoidosis remains an unusual entity, but it may be that histologic involvement of the pleura is more common than generally appreciated.", "contents": "Spectrum of pleural involvement in sarcoidosis. Pleural involvement has generally been considered an unusual aspect of sarcoidosis. In this paper, five previously unreported cases of sarcoidosis involving the pleura were discussed. Pleural sarcoidosis may be manifested by the presence of a pleural effusion, and the diagnosis is based on the exclusion of all other possible causes and the demonstration of noncaseating granulomas in the pleura. When the pleura is involved without effusion, it may only be recognized if noncaseating granulomas involving the pleura are looked for specifically. Including the five cases form this study, there have been 73 cases of pleural sarcoidosis reported, but only 37 have been verified by histologic evidence. When strict diagnostic criteria are used, clinical involvement of the pleura in sarsoidosis remains an unusual entity, but it may be that histologic involvement of the pleura is more common than generally appreciated."} {"id": "PMID:1259501", "title": "Intravenously injected marihuana syndrome.", "content": "Two patients who injected marihuana intravenously developed a syndrome of hypotension, renal insufficiency, thrombocytopenia, and rhabdomyolysis. These clinical abnormalities appear to be reversible without residua.", "contents": "Intravenously injected marihuana syndrome. Two patients who injected marihuana intravenously developed a syndrome of hypotension, renal insufficiency, thrombocytopenia, and rhabdomyolysis. These clinical abnormalities appear to be reversible without residua."} {"id": "PMID:1259502", "title": "Early diastolic sound associated with mitral valve prolapse.", "content": "A patient with the prolapsing mitral valve syndrome demonstrated a most striking early diastolic sound. Noninvasive study with phonocardiograms, external pulse recordings, and echocardiograms lead us to believe that the sound may be related to the initial opening movement of the mitral valve. To our knowledge, such a mechanism for the production of a diastolic sound has not been previously reported.", "contents": "Early diastolic sound associated with mitral valve prolapse. A patient with the prolapsing mitral valve syndrome demonstrated a most striking early diastolic sound. Noninvasive study with phonocardiograms, external pulse recordings, and echocardiograms lead us to believe that the sound may be related to the initial opening movement of the mitral valve. To our knowledge, such a mechanism for the production of a diastolic sound has not been previously reported."} {"id": "PMID:1259503", "title": "Left main coronary artery spasm. A potential cause for angiographic misdiagnosis of severe coronary artery disease.", "content": "Two patients had catheter-induced spasm of the left main coronary artery during diagnostic coronary arteriography. One patient had no coronary artery disease, and the other had minimal disease of the right coronary artery. Spasm was relieved by nitrates; however, in one patient several doses were needed over 35 minutes. Catheter-induced spasm must be considered in the diagnosis of left main coronary artery disease, particularly on a patient with isolated left main coronary artery disease.", "contents": "Left main coronary artery spasm. A potential cause for angiographic misdiagnosis of severe coronary artery disease. Two patients had catheter-induced spasm of the left main coronary artery during diagnostic coronary arteriography. One patient had no coronary artery disease, and the other had minimal disease of the right coronary artery. Spasm was relieved by nitrates; however, in one patient several doses were needed over 35 minutes. Catheter-induced spasm must be considered in the diagnosis of left main coronary artery disease, particularly on a patient with isolated left main coronary artery disease."} {"id": "PMID:1259504", "title": "The Jewish Hospital of St Louis Therapeutic Grand Rounds No. 14. Hypersensitivity pneumonitis.", "content": "Two examples of immunologically mediated diseases of the lung have been discussed. The first, extrinsic allergic alveolitis, is caused by sensitivity to inhalation of an organic dust. It is largely a restrictive type of lung disease and is probably caused by a combination of type 3 and type 4 allergic reactions. The second disease, allergic bronchopulmonary aspergillosis, is caused by a type 1 and type 3 allergic response to Aspergillus antigen in a basically atopic, generally asthmatic individual. It is vital to keep the diagnostic index of suspicion high so as to recognize these diseases early enough to prevent irreparable tissue damage. Extrinsic allergic alveolitis may masquerade as idopathic pulmonary fibrosis or Hamman-Rich syndrome. Allergic aspergillosis may be called Loeffler pneumonia or PIE syndrome (pulmonary infiltrates with eosiniphilia). Failure to diagnose properly may result in extensive pulmonary fibrosis or bronchiectasis and condemn the patient to a lifetime as a pulmonary cripple.", "contents": "The Jewish Hospital of St Louis Therapeutic Grand Rounds No. 14. Hypersensitivity pneumonitis. Two examples of immunologically mediated diseases of the lung have been discussed. The first, extrinsic allergic alveolitis, is caused by sensitivity to inhalation of an organic dust. It is largely a restrictive type of lung disease and is probably caused by a combination of type 3 and type 4 allergic reactions. The second disease, allergic bronchopulmonary aspergillosis, is caused by a type 1 and type 3 allergic response to Aspergillus antigen in a basically atopic, generally asthmatic individual. It is vital to keep the diagnostic index of suspicion high so as to recognize these diseases early enough to prevent irreparable tissue damage. Extrinsic allergic alveolitis may masquerade as idopathic pulmonary fibrosis or Hamman-Rich syndrome. Allergic aspergillosis may be called Loeffler pneumonia or PIE syndrome (pulmonary infiltrates with eosiniphilia). Failure to diagnose properly may result in extensive pulmonary fibrosis or bronchiectasis and condemn the patient to a lifetime as a pulmonary cripple."} {"id": "PMID:1259505", "title": "Self-hemodialysis. The optimal mode of dialytic therapy.", "content": "Maintenance hemodialysis is presently the mainstay of treatment for the majority of patients with end-stage renal disease. There has been disagreement, however, as to what form the delivery of dialysis should take-self-dialysis, at home, or in-center, as opposed to in-center, limited-care dialysis. This review of the recent literature strongly supports self-dialysis as the optimal form of therapy, since the cost is less, and survival and rehabilation are better than with limited-care dialysis. We conclude that a greater effort should be expended to encourage and even direct patients toward this form of therapy.", "contents": "Self-hemodialysis. The optimal mode of dialytic therapy. Maintenance hemodialysis is presently the mainstay of treatment for the majority of patients with end-stage renal disease. There has been disagreement, however, as to what form the delivery of dialysis should take-self-dialysis, at home, or in-center, as opposed to in-center, limited-care dialysis. This review of the recent literature strongly supports self-dialysis as the optimal form of therapy, since the cost is less, and survival and rehabilation are better than with limited-care dialysis. We conclude that a greater effort should be expended to encourage and even direct patients toward this form of therapy."} {"id": "PMID:1259507", "title": "[Antibodies in venereal sarcoma in dogs].", "content": "Neoplastic cell suspensions prepared from fourteen spontaneous and three transplanted vereal sarcomas of the dog were studied by microcytotoxicity and immunofluorescence tests. Serum and cell-surface antibodies were found in all cases. These antibodies were not capable of activating canine complement. Most likely these antibodies are not cytotoxic in vivo, but rather act by enhancing tumor growth.", "contents": "[Antibodies in venereal sarcoma in dogs]. Neoplastic cell suspensions prepared from fourteen spontaneous and three transplanted vereal sarcomas of the dog were studied by microcytotoxicity and immunofluorescence tests. Serum and cell-surface antibodies were found in all cases. These antibodies were not capable of activating canine complement. Most likely these antibodies are not cytotoxic in vivo, but rather act by enhancing tumor growth."} {"id": "PMID:1259509", "title": "[Distribution of a cell with intracytoplasmic crystal and crystaloid material in the small and large intestine of the rat and mouse].", "content": "In suckling and adult rats, distribution in the small and large intestine of crystal-like containing cell was studied and was compared with that of crystal containing cell in the mouse. In the former, cell predominates in cecum and in the latter in the ileum. Numerical differences were statistical significant. It was postulated that these cells might be different. Up to date, they have been regarded as the same cell by other authors and are known as globular leucocyte.", "contents": "[Distribution of a cell with intracytoplasmic crystal and crystaloid material in the small and large intestine of the rat and mouse]. In suckling and adult rats, distribution in the small and large intestine of crystal-like containing cell was studied and was compared with that of crystal containing cell in the mouse. In the former, cell predominates in cecum and in the latter in the ileum. Numerical differences were statistical significant. It was postulated that these cells might be different. Up to date, they have been regarded as the same cell by other authors and are known as globular leucocyte."} {"id": "PMID:1259508", "title": "[Depression and Herpex simplex infections].", "content": "It has been mentioned that herpes simplex antibodies are increased in depressed patients. In the present study, serums from 21 patients with reactive depressions, nine with psychotic depression, 33 schizophrenic and 15 normal controls were studied, and herpes simplex antibodies were measured. Neither was statistically significant difference found between any of the groups nor could antibody titres be correlated with severity of depression measured by a psychiatric rating scale. The authors review the pertinent literature, and state that although antibody tires do not correlated with psychiatric diagnosis, there still exists the possibility that latent brain viral infections might trigger depressive episodes in some cases.", "contents": "[Depression and Herpex simplex infections]. It has been mentioned that herpes simplex antibodies are increased in depressed patients. In the present study, serums from 21 patients with reactive depressions, nine with psychotic depression, 33 schizophrenic and 15 normal controls were studied, and herpes simplex antibodies were measured. Neither was statistically significant difference found between any of the groups nor could antibody titres be correlated with severity of depression measured by a psychiatric rating scale. The authors review the pertinent literature, and state that although antibody tires do not correlated with psychiatric diagnosis, there still exists the possibility that latent brain viral infections might trigger depressive episodes in some cases."} {"id": "PMID:1259510", "title": "[Type A and C viruses particles in murine lymphoma L 5178Y].", "content": "The presence of virus particles and their possible mechanism of excretion was studied in cells of murine lymphoma L 5178Y grown intraperitoneally. Malignant cells obtained from 10 mice bearing this lymphoma were studied with the electron microscope. In 96% of the cells 1 to 30 viroid particles (VP) type C (VP-C) clumped or isolated, averaging six per cell were observed. Isolated VP-C were commonly seen within endoplasmic reticulum or budding off from cell surface. Such a finding was regarded as the mechanism of excretion. However, with the present findings it is not possible to draw any conclusions upon the oncogenic nature of the virus particles described herein.", "contents": "[Type A and C viruses particles in murine lymphoma L 5178Y]. The presence of virus particles and their possible mechanism of excretion was studied in cells of murine lymphoma L 5178Y grown intraperitoneally. Malignant cells obtained from 10 mice bearing this lymphoma were studied with the electron microscope. In 96% of the cells 1 to 30 viroid particles (VP) type C (VP-C) clumped or isolated, averaging six per cell were observed. Isolated VP-C were commonly seen within endoplasmic reticulum or budding off from cell surface. Such a finding was regarded as the mechanism of excretion. However, with the present findings it is not possible to draw any conclusions upon the oncogenic nature of the virus particles described herein."} {"id": "PMID:1259511", "title": "Isolation and growth rates of methanol utilizing Rhodospirillaceae.", "content": "38 pure culture strains belonging to seven species of the Rhodospirillaceae were isolated from 39 methanol enrichment cultures inoculated with water and mud samples of different habitats. None of the strains exhibited doubling times shorter than 10 h in methanol-bicarbonate media.", "contents": "Isolation and growth rates of methanol utilizing Rhodospirillaceae. 38 pure culture strains belonging to seven species of the Rhodospirillaceae were isolated from 39 methanol enrichment cultures inoculated with water and mud samples of different habitats. None of the strains exhibited doubling times shorter than 10 h in methanol-bicarbonate media."} {"id": "PMID:1259512", "title": "Preparation and partial characterization of a Lactobacillus lactis bacteriophage.", "content": "High-titer lysates of a bacteriophage active against Lactobacillus lactis were prepared from liquid cultures as well as from areas of confluent lysis in soft-agar overlayers. Phage concentration and purification were accomplished by means of polyethylene glycol precipitation, differential centrifugation. The buoyant density of this phage in cesium chloride was 1.4795 g/ml. Characterization of phage growth cycle by one-step growth experiments under optimal conditions showed that the latent period was about 120 min, that the rise period lasted approx. 130 min, and that the average burst-size was about 80.", "contents": "Preparation and partial characterization of a Lactobacillus lactis bacteriophage. High-titer lysates of a bacteriophage active against Lactobacillus lactis were prepared from liquid cultures as well as from areas of confluent lysis in soft-agar overlayers. Phage concentration and purification were accomplished by means of polyethylene glycol precipitation, differential centrifugation. The buoyant density of this phage in cesium chloride was 1.4795 g/ml. Characterization of phage growth cycle by one-step growth experiments under optimal conditions showed that the latent period was about 120 min, that the rise period lasted approx. 130 min, and that the average burst-size was about 80."} {"id": "PMID:1259513", "title": "Studies on utilization of 2-ketoglutarate, glutamate and other amino acids by the unicellular alga Cyanidium caldarium.", "content": "Two strains of Cyandium caladarium which possess different biochemical and nutritional characteristics were examined with respect to their ability to utilize amino acids or 2-ketoglutarate as substrates. One strain utilizes alanine, glutamate or aspartate as nitrogen sources, and glutamate, alanine, or 2-ketoglutarate as carbon and energy sources for growth in the dark. The growth rate in the dark on 2-ketoglutarate is almost twice as high or higher than that on glutamate or alanine. During growth or incubation of this alga on amino acids, large amounts of ammonia are formed; however, ammonia formation is strongly inhibited by 2-ketoglutarate. The capacity of the alga and develops fully only when the cells are grown or incubated in the presence of glutamate.", "contents": "Studies on utilization of 2-ketoglutarate, glutamate and other amino acids by the unicellular alga Cyanidium caldarium. Two strains of Cyandium caladarium which possess different biochemical and nutritional characteristics were examined with respect to their ability to utilize amino acids or 2-ketoglutarate as substrates. One strain utilizes alanine, glutamate or aspartate as nitrogen sources, and glutamate, alanine, or 2-ketoglutarate as carbon and energy sources for growth in the dark. The growth rate in the dark on 2-ketoglutarate is almost twice as high or higher than that on glutamate or alanine. During growth or incubation of this alga on amino acids, large amounts of ammonia are formed; however, ammonia formation is strongly inhibited by 2-ketoglutarate. The capacity of the alga and develops fully only when the cells are grown or incubated in the presence of glutamate."} {"id": "PMID:1259514", "title": "Enrichment and isolation of nitrogen fixing hydrogen bacteria.", "content": "An enrichment method for nitrogen fixing hydrogen bacteria is described. The procedure invariably resulted in the isolation of yellow-pigmented coryneform bacterial strains assigned to Corynebacterium autotrophicum. The procedure included a serial transfer in an ammonium-free mineral liquid medium under an atmosphere of 10% hydrogen, 5% oxygen, 10% carbon dioxide and 75% nitrogen, followed by a short alkali treatment and by streaking on nutrient broth-succinate agar. The ability to fix nitrogen was confirmed by the acetylene reduction test and by 15N2 incorporation.", "contents": "Enrichment and isolation of nitrogen fixing hydrogen bacteria. An enrichment method for nitrogen fixing hydrogen bacteria is described. The procedure invariably resulted in the isolation of yellow-pigmented coryneform bacterial strains assigned to Corynebacterium autotrophicum. The procedure included a serial transfer in an ammonium-free mineral liquid medium under an atmosphere of 10% hydrogen, 5% oxygen, 10% carbon dioxide and 75% nitrogen, followed by a short alkali treatment and by streaking on nutrient broth-succinate agar. The ability to fix nitrogen was confirmed by the acetylene reduction test and by 15N2 incorporation."} {"id": "PMID:1259515", "title": "Stoffwechselprodukte von mikroorganismen. 154. Mitteilung. Nikkomycin, ein neuer hemmstoff der chitinsynthese bei pilzen.", "content": "From the fermentation broth of Streptomyces tendae T\u00fc 901 a substance was isolated which inhibits the growth of several fungi. The new antibiotic affects the chitchin biosynthesis. Its structure was identified by mass spectrometry of the products obtained after chemical degradation. Nikkomycin is a nucleoside-peptide antibiotic consisting of uracil, an amino hexuronic acid and a new amino acid containing a pyridin ring.", "contents": "Stoffwechselprodukte von mikroorganismen. 154. Mitteilung. Nikkomycin, ein neuer hemmstoff der chitinsynthese bei pilzen. From the fermentation broth of Streptomyces tendae T\u00fc 901 a substance was isolated which inhibits the growth of several fungi. The new antibiotic affects the chitchin biosynthesis. Its structure was identified by mass spectrometry of the products obtained after chemical degradation. Nikkomycin is a nucleoside-peptide antibiotic consisting of uracil, an amino hexuronic acid and a new amino acid containing a pyridin ring."} {"id": "PMID:1259517", "title": "Occurrence of pppApp-synthesizing activity in actinomycetes and isolation of purine nucleotide pyrophosphotransferase.", "content": "The occurrence of adenosine 5'-triphosphate-3'diphosphate-synthesizing activity was detected in five strains of actinomycetes; Streptomyces morookaensis, Streptomyces aspergilloides, Streptomyces hachijoensis, tactinomyces violascens and Streptoverticillium septatum, out of 825 strains of actinomycetes, bacteria, fungi and fungi imperficti. Purine nucleotide pyrophosphotransferase were extracellularly excreted associating with the cell growth, and were purified partially or to apparent homogeneiety from the culture filtrate. The enzymes are a monomeric protein with molecular weight of 18,000-26,000 and synthesize adenosine, guanosine and inosine 5'-phosphate (mono, di or tri)-3'-diphosphate such as pApp, ppA pp, pppApp, pGpp, ppGpp, pppGpp, and pppIpp by transferring a pyrophosphoryl group from the 5'-position of ATP, dATP and ppApp to the 3'-position of purine nucleotides in the presence of a divalent cation and in alkaline state.", "contents": "Occurrence of pppApp-synthesizing activity in actinomycetes and isolation of purine nucleotide pyrophosphotransferase. The occurrence of adenosine 5'-triphosphate-3'diphosphate-synthesizing activity was detected in five strains of actinomycetes; Streptomyces morookaensis, Streptomyces aspergilloides, Streptomyces hachijoensis, tactinomyces violascens and Streptoverticillium septatum, out of 825 strains of actinomycetes, bacteria, fungi and fungi imperficti. Purine nucleotide pyrophosphotransferase were extracellularly excreted associating with the cell growth, and were purified partially or to apparent homogeneiety from the culture filtrate. The enzymes are a monomeric protein with molecular weight of 18,000-26,000 and synthesize adenosine, guanosine and inosine 5'-phosphate (mono, di or tri)-3'-diphosphate such as pApp, ppA pp, pppApp, pGpp, ppGpp, pppGpp, and pppIpp by transferring a pyrophosphoryl group from the 5'-position of ATP, dATP and ppApp to the 3'-position of purine nucleotides in the presence of a divalent cation and in alkaline state."} {"id": "PMID:1259516", "title": "Structure and composition of intracytoplasmic membranes of Ectothiorhodospira mobilis.", "content": "The lamellar membrane stacks of Ectothiorhodospira mobilis were isolated and purified by a combination of lysozyme and osmotic shock treatment, followed by differential and density gradient centrifugation. Preparations of lamellar membranes were enriched at least 2.4-fold in the ratio of bacteriochlorophyll a to protein. Thin-sectioning, negative staining, platinum-carbon shadowing and freeze-etching were used to study the architecture of the membrane units. Both platinum-carbon shadowing and freeze-etching showed the outer-surfaces of the isolated lamellar membrane stacks to be relatively smooth. Particles averaging 7 nm in diameter were seen on several faces following freeze-etching.", "contents": "Structure and composition of intracytoplasmic membranes of Ectothiorhodospira mobilis. The lamellar membrane stacks of Ectothiorhodospira mobilis were isolated and purified by a combination of lysozyme and osmotic shock treatment, followed by differential and density gradient centrifugation. Preparations of lamellar membranes were enriched at least 2.4-fold in the ratio of bacteriochlorophyll a to protein. Thin-sectioning, negative staining, platinum-carbon shadowing and freeze-etching were used to study the architecture of the membrane units. Both platinum-carbon shadowing and freeze-etching showed the outer-surfaces of the isolated lamellar membrane stacks to be relatively smooth. Particles averaging 7 nm in diameter were seen on several faces following freeze-etching."} {"id": "PMID:1259518", "title": "Torulopsis spandovensis sp. n., a new yeast from beer.", "content": "A new species of the genus Torulopsis has been isolated from several different samples of German Pilsener Beer. A description of the new species is given.", "contents": "Torulopsis spandovensis sp. n., a new yeast from beer. A new species of the genus Torulopsis has been isolated from several different samples of German Pilsener Beer. A description of the new species is given."} {"id": "PMID:1259519", "title": "Bioenergetic aspects of aerobic growth of Klebsiella aerogenes NCTC 418 in carbon-limited and carbon-sufficient chemostat culture.", "content": "Carbon-limited chemostat cultures of Klebsiella aerogenes NCTC 418 consumed more oxygen per unit of cell synthesis when growing on mannitol or glycerol than when growing on glucose; and since the \"maintenance\" requirements were similar, this suggested that the extra reducing equivalents present in these compounds were oxidized wastefully. By comparison with carbon-limited cultures, carbon-sufficient cultures that were ammonia-, sulphate- or phosphate-limited generally consumed considerably more oxygen per unit of cell synthesis, particularly at low growth rates. Thus, according to the theory of Pirt, these carbon-sufficient cultures had a greatly increased \"maintenance energy\" requirement but nevertheless used the remaining energy with a much increased efficiency compared with carbon-limited cultures. This, we suggest, is a false conclusion which stems from the basic assumption that the maintenance requirement does not change with growth rate.", "contents": "Bioenergetic aspects of aerobic growth of Klebsiella aerogenes NCTC 418 in carbon-limited and carbon-sufficient chemostat culture. Carbon-limited chemostat cultures of Klebsiella aerogenes NCTC 418 consumed more oxygen per unit of cell synthesis when growing on mannitol or glycerol than when growing on glucose; and since the \"maintenance\" requirements were similar, this suggested that the extra reducing equivalents present in these compounds were oxidized wastefully. By comparison with carbon-limited cultures, carbon-sufficient cultures that were ammonia-, sulphate- or phosphate-limited generally consumed considerably more oxygen per unit of cell synthesis, particularly at low growth rates. Thus, according to the theory of Pirt, these carbon-sufficient cultures had a greatly increased \"maintenance energy\" requirement but nevertheless used the remaining energy with a much increased efficiency compared with carbon-limited cultures. This, we suggest, is a false conclusion which stems from the basic assumption that the maintenance requirement does not change with growth rate."} {"id": "PMID:1259520", "title": "Isolation of regulatory mutants of Pseudomonas acidovorans by use of amino acid analogs.", "content": "Mutants resistance to various combinations of threonine, lysine and/or their analogs were obtained and characterized in Pseudomonas acidovorans. In particular, mutants resistant to aminoethylcysteine had a dihydrodipicolinate synthetase insensitive to lysine inhibition whereas mutants resistant to threonine plus a low concentration of aminoethylcysteine had a feedback-insensitive aspartokinase.", "contents": "Isolation of regulatory mutants of Pseudomonas acidovorans by use of amino acid analogs. Mutants resistance to various combinations of threonine, lysine and/or their analogs were obtained and characterized in Pseudomonas acidovorans. In particular, mutants resistant to aminoethylcysteine had a dihydrodipicolinate synthetase insensitive to lysine inhibition whereas mutants resistant to threonine plus a low concentration of aminoethylcysteine had a feedback-insensitive aspartokinase."} {"id": "PMID:1259521", "title": "The effect of neuroleptics on serum prolactin in schizophrenic patients.", "content": "Serum prolactin levels were studied before and during long-term administration of phenothiazines on a twice daily schedule to 27 newly admitted schizophrenic patients. An increase in serum prolactin is believed to be a reflection of inhibition of dopamine receptors in the hypothalamopituitary axis. By 72 hours after the initiation of treatment, all 27 patients had persistently elevated serum prolactin levels averaging 3.2-fold and 3.8-fold in men and women, respectively. There was a lag between clinical response and dopamine blockade, as indicated by serum prolactin levels in most patients. Serum prolactin levels remained elevated during the one- to three-month period subjects were studied, suggesting there was no tolerance to this effect of phenothiazines. Serum prolactin levels tended to be higher with thioridazine than on equivalent doses of chlorpromazine or trifluoperazine hydrochloride. There was some evidence that the magnitude of the serum prolactin elevation correlated with clinical response. After cessation of phenothiazines, serum prolactin levels rapidly reverted to normal within 48 to 96 hours.", "contents": "The effect of neuroleptics on serum prolactin in schizophrenic patients. Serum prolactin levels were studied before and during long-term administration of phenothiazines on a twice daily schedule to 27 newly admitted schizophrenic patients. An increase in serum prolactin is believed to be a reflection of inhibition of dopamine receptors in the hypothalamopituitary axis. By 72 hours after the initiation of treatment, all 27 patients had persistently elevated serum prolactin levels averaging 3.2-fold and 3.8-fold in men and women, respectively. There was a lag between clinical response and dopamine blockade, as indicated by serum prolactin levels in most patients. Serum prolactin levels remained elevated during the one- to three-month period subjects were studied, suggesting there was no tolerance to this effect of phenothiazines. Serum prolactin levels tended to be higher with thioridazine than on equivalent doses of chlorpromazine or trifluoperazine hydrochloride. There was some evidence that the magnitude of the serum prolactin elevation correlated with clinical response. After cessation of phenothiazines, serum prolactin levels rapidly reverted to normal within 48 to 96 hours."} {"id": "PMID:1259522", "title": "Children of psychotic mothers. An evaluation of 1-year-olds on a test of object permanence.", "content": "Fifteen 1-year-old infants at high risk for later psychopathologic behavior were tested on the Piaget Object Scale. Their performance was compared to that of a matched group of controls at low risk. Results indicate a trend in the high-risk group toward lowered object scale performance. Affective styles were found to vary between the groups. The high-risk infants, particularly those with low scores on the object scale, demonstrated more intense anxiety.", "contents": "Children of psychotic mothers. An evaluation of 1-year-olds on a test of object permanence. Fifteen 1-year-old infants at high risk for later psychopathologic behavior were tested on the Piaget Object Scale. Their performance was compared to that of a matched group of controls at low risk. Results indicate a trend in the high-risk group toward lowered object scale performance. Affective styles were found to vary between the groups. The high-risk infants, particularly those with low scores on the object scale, demonstrated more intense anxiety."} {"id": "PMID:1259523", "title": "Depressed 5-hydroxyindole levels associated with hyperactive and aggressive behavior. Relationship to drug response.", "content": "Monitoring of 5-hydroxyindole (5-HI) levels in blood in hyperactive institutionalized mentally retarded patients before and after drug therapy revealed depression of 5-HI levels in 83% of hyperactive patients. In these patients with low serotonin levels, elevation of 5-HI levels in blood into the normal range by administration of a variety of psychoactive agents was associated with the disappearance of the hyperkinetic syndrome. Patients who remained hyperactive continued to have low 5-HI levels. Return of hyperactivity upon withdrawal of meidication in patients who were previously well controlled was associated with a fall in 5-HI levels. Adverse responses were seen in these patients when they were treated with medications usually tending to lower 5-HI levels in blood. Medications used in the treatment of hyperactivity may be classified as to whether they usually elevate, lower, or have no significant effect on 5-HI levels in blood.", "contents": "Depressed 5-hydroxyindole levels associated with hyperactive and aggressive behavior. Relationship to drug response. Monitoring of 5-hydroxyindole (5-HI) levels in blood in hyperactive institutionalized mentally retarded patients before and after drug therapy revealed depression of 5-HI levels in 83% of hyperactive patients. In these patients with low serotonin levels, elevation of 5-HI levels in blood into the normal range by administration of a variety of psychoactive agents was associated with the disappearance of the hyperkinetic syndrome. Patients who remained hyperactive continued to have low 5-HI levels. Return of hyperactivity upon withdrawal of meidication in patients who were previously well controlled was associated with a fall in 5-HI levels. Adverse responses were seen in these patients when they were treated with medications usually tending to lower 5-HI levels in blood. Medications used in the treatment of hyperactivity may be classified as to whether they usually elevate, lower, or have no significant effect on 5-HI levels in blood."} {"id": "PMID:1259524", "title": "Heroin addiction. Sequential treatment employing pharmacologic supports.", "content": "A system of treatment for heroin addiction is proposed under the acronym STEPS (sequential treatment employing pharmacologic supports). Small steps characterized by decreasing narcotic-induced euphoria and increasing social rehabilitation are expected eventually to bring the addict to an abstinent and well-functioning state, if that is possible. The dichotomous assessment of \"success\" or \"failure\" is rejected in favor of the expectation of partial and temporary improvements, as with any chronic relapsing disease.", "contents": "Heroin addiction. Sequential treatment employing pharmacologic supports. A system of treatment for heroin addiction is proposed under the acronym STEPS (sequential treatment employing pharmacologic supports). Small steps characterized by decreasing narcotic-induced euphoria and increasing social rehabilitation are expected eventually to bring the addict to an abstinent and well-functioning state, if that is possible. The dichotomous assessment of \"success\" or \"failure\" is rejected in favor of the expectation of partial and temporary improvements, as with any chronic relapsing disease."} {"id": "PMID:1259525", "title": "Behavioral and social effects of heroin self-administration and withdrawal.", "content": "Behavioral and social reactions to intravenously administered heroin were studied during a 33-day experimental addiction cycle. Three groups of four subject volunteers were allowed to self-administer heroin for a ten-day period as part of a longer study of oplate antagonists. Data relevant to sleep patterns, energy expenditure, social interaction, and other observable behaviors were collected during hourly observations. Comparison of behavioral differences before and after drug administration indicated few significant acute reactions. Reactions to long-term heroin self-administration were most pronounced in the areas of sleep behavior and social interaction. Subjects tended to sleep less, especially during the initial period of acquisition, and to withdraw more from social contact. No changes were noted in energy expenditure during waking hours. The results were interpreted in terms of physiological tolerance, central nervous system arousal, and sleep deprivation.", "contents": "Behavioral and social effects of heroin self-administration and withdrawal. Behavioral and social reactions to intravenously administered heroin were studied during a 33-day experimental addiction cycle. Three groups of four subject volunteers were allowed to self-administer heroin for a ten-day period as part of a longer study of oplate antagonists. Data relevant to sleep patterns, energy expenditure, social interaction, and other observable behaviors were collected during hourly observations. Comparison of behavioral differences before and after drug administration indicated few significant acute reactions. Reactions to long-term heroin self-administration were most pronounced in the areas of sleep behavior and social interaction. Subjects tended to sleep less, especially during the initial period of acquisition, and to withdraw more from social contact. No changes were noted in energy expenditure during waking hours. The results were interpreted in terms of physiological tolerance, central nervous system arousal, and sleep deprivation."} {"id": "PMID:1259526", "title": "Cannabis psychosis and paranoid schizophrenia.", "content": "The initial clinical symptoms of 25 consecutive cases of cannabis psychosis of the paranoid type and 25 consecutive cases of paranoid schizophrenia were studied and compared, in order to delineate features that would enable a differentiation of the two conditions. It was observed that the patients with cannabis psychosis substantially differed in terms of behavioral manifestations. Most of these patients were violent and panicky and demonstrated bizzare behavior, but they possessed some insight into the nature of their illness. Schizophrenic patients manifested these disturbances and characteristics less frequently. Subjects with cannabis psychosis showed rapid ideation and flight of ideas, whereas the characteristic schizophrenic thought-disorder was found mostly in schizophrenic patients.", "contents": "Cannabis psychosis and paranoid schizophrenia. The initial clinical symptoms of 25 consecutive cases of cannabis psychosis of the paranoid type and 25 consecutive cases of paranoid schizophrenia were studied and compared, in order to delineate features that would enable a differentiation of the two conditions. It was observed that the patients with cannabis psychosis substantially differed in terms of behavioral manifestations. Most of these patients were violent and panicky and demonstrated bizzare behavior, but they possessed some insight into the nature of their illness. Schizophrenic patients manifested these disturbances and characteristics less frequently. Subjects with cannabis psychosis showed rapid ideation and flight of ideas, whereas the characteristic schizophrenic thought-disorder was found mostly in schizophrenic patients."} {"id": "PMID:1259527", "title": "The medical safety of the combined usage of disulfiram and methadone. Pharmacological treatment for alcoholic heroin addicts.", "content": "The results of hematology and blood chemistry tests were examined in eight methadone maintenance patients who had been treated concurrently for alcoholism with disulfiram (Antabuse). There were no apparent major differences between the results of tests run prior to the initiation of the disulfiram treatment and subsequent tests run up to 16 months after treatment was begun. There was a trend toward normalization of serum glutamic oxaloacetic transaminase (SGOT) values. The results suggested no contraindications to this combined pharmacological treatment.", "contents": "The medical safety of the combined usage of disulfiram and methadone. Pharmacological treatment for alcoholic heroin addicts. The results of hematology and blood chemistry tests were examined in eight methadone maintenance patients who had been treated concurrently for alcoholism with disulfiram (Antabuse). There were no apparent major differences between the results of tests run prior to the initiation of the disulfiram treatment and subsequent tests run up to 16 months after treatment was begun. There was a trend toward normalization of serum glutamic oxaloacetic transaminase (SGOT) values. The results suggested no contraindications to this combined pharmacological treatment."} {"id": "PMID:1259528", "title": "Development of reference systems for automatic identification of clinical isolates of bacteria.", "content": "The reported work describes experiments on automatic identification based on a material of 636 clinical isolates of bacteria. It is shown that three different and mutually independent automatic identification principles produce almost identical identification conclusions. It is also shown that an automatic procedure which continuously corrects the basic classification gives results which are independent of the classification background. Automatic correction logics develop conventionally-based, as well as numerically-based initial reference systems toward almost similar solutions. This may indicate that automated identification methods based on numerical classifications possess general validity.", "contents": "Development of reference systems for automatic identification of clinical isolates of bacteria. The reported work describes experiments on automatic identification based on a material of 636 clinical isolates of bacteria. It is shown that three different and mutually independent automatic identification principles produce almost identical identification conclusions. It is also shown that an automatic procedure which continuously corrects the basic classification gives results which are independent of the classification background. Automatic correction logics develop conventionally-based, as well as numerically-based initial reference systems toward almost similar solutions. This may indicate that automated identification methods based on numerical classifications possess general validity."} {"id": "PMID:1259529", "title": "Antibiotic action of beta-ursolic acid.", "content": "The antimicrobial action of beta-ursolic acid (triterpenoid sapogenin from the ursan group) has been studied. At the concentration of 300 mug/ml, this substance inhibited growth of all strains of staphylococci investigated. MIC for Gram-positive bacteria ranged between 50 and 500 mug/ml, and 100 to 800 mug/ml for Gram-negative bacteria and yeasts. Acquired resistance to beta-ursolic acid was transient.", "contents": "Antibiotic action of beta-ursolic acid. The antimicrobial action of beta-ursolic acid (triterpenoid sapogenin from the ursan group) has been studied. At the concentration of 300 mug/ml, this substance inhibited growth of all strains of staphylococci investigated. MIC for Gram-positive bacteria ranged between 50 and 500 mug/ml, and 100 to 800 mug/ml for Gram-negative bacteria and yeasts. Acquired resistance to beta-ursolic acid was transient."} {"id": "PMID:1259530", "title": "A trial of using antibodies as carriers of alkylating agents. II. Evaluation of ability to form 32P-cyclophosphamide + immune antibody complexes with homologous antigen.", "content": "32P-cyclophosphamide was found to combine with gamma-globulin fractions of immune sera. Immune sera incubated with 32P-cyclophosphamide retained ability to react specifically with homologous antigen in vitro in the system: MN antigens of human erythrocytes + rabbit anti-MN antibody, and probably reacted selectively with target antigens in vivo in the system: antigens of guinea pig kidney tissue + rabbit antibodies against these antigens. Hemagglutination, passive hemagglutination and precipitation in agar gel tests were used in the experiments. Ability to combine of the immune antibody + 32P-cyclophosphamide complex with homologous antigens was evaluated by measurements of radioactivity of studied materials (erythrocyte agglutinates and organ homogenates). The results indicate feasibility of using immune antibodies as carriers of cytostatic agents.", "contents": "A trial of using antibodies as carriers of alkylating agents. II. Evaluation of ability to form 32P-cyclophosphamide + immune antibody complexes with homologous antigen. 32P-cyclophosphamide was found to combine with gamma-globulin fractions of immune sera. Immune sera incubated with 32P-cyclophosphamide retained ability to react specifically with homologous antigen in vitro in the system: MN antigens of human erythrocytes + rabbit anti-MN antibody, and probably reacted selectively with target antigens in vivo in the system: antigens of guinea pig kidney tissue + rabbit antibodies against these antigens. Hemagglutination, passive hemagglutination and precipitation in agar gel tests were used in the experiments. Ability to combine of the immune antibody + 32P-cyclophosphamide complex with homologous antigens was evaluated by measurements of radioactivity of studied materials (erythrocyte agglutinates and organ homogenates). The results indicate feasibility of using immune antibodies as carriers of cytostatic agents."} {"id": "PMID:1259531", "title": "Blastic transformation of lymphocytes in in vitro cultures under the influence of phytohemagglutinin and pokeweek mitogen in patients with glomerulonephritis treated over long periods of time with immunosuppressive drugs.", "content": "In vitro reactivity of lymphocytes to phytohemagglutinin (PHA) and pokeweek mitogen (PWM) was studied in 17 patients with chronic glomerulonephritis treated systematically over many months (average, 23 months) with immunosuppressive drugs (prednisone, indomethacin, azathioprine, cyclophosphamide). Blastic transformation of lymphocytes in cultures stimulated with PHA was tested three times: before beginning of treatment, during the course of therapy with full doses, and after prolonged ambulatory treatment with maintenance doses. The degree of blastic transformation under the influence of PWM was determined only after periods of many months of treatment with chemical immunosuppresors. The results showed that neither treatment of chronic glomerulonephritis for several weeks with full doses, nor subsequent prolonged administration (for periods of tens of months) of maintenance doses of immunosuppresors regularly inhibit blastic transformation of lymphocytes stimulated with PHA. Similar observations were made using PWM after many months of immunosuppressive therapy. Reactivity of lymphocytes to PWM in all patients resembled reactivity to PHA.", "contents": "Blastic transformation of lymphocytes in in vitro cultures under the influence of phytohemagglutinin and pokeweek mitogen in patients with glomerulonephritis treated over long periods of time with immunosuppressive drugs. In vitro reactivity of lymphocytes to phytohemagglutinin (PHA) and pokeweek mitogen (PWM) was studied in 17 patients with chronic glomerulonephritis treated systematically over many months (average, 23 months) with immunosuppressive drugs (prednisone, indomethacin, azathioprine, cyclophosphamide). Blastic transformation of lymphocytes in cultures stimulated with PHA was tested three times: before beginning of treatment, during the course of therapy with full doses, and after prolonged ambulatory treatment with maintenance doses. The degree of blastic transformation under the influence of PWM was determined only after periods of many months of treatment with chemical immunosuppresors. The results showed that neither treatment of chronic glomerulonephritis for several weeks with full doses, nor subsequent prolonged administration (for periods of tens of months) of maintenance doses of immunosuppresors regularly inhibit blastic transformation of lymphocytes stimulated with PHA. Similar observations were made using PWM after many months of immunosuppressive therapy. Reactivity of lymphocytes to PWM in all patients resembled reactivity to PHA."} {"id": "PMID:1259532", "title": "Influence of immunosuppressive drugs on activity of lymph node permeability factor (LNPF).", "content": "The influence of selected immunosuppressive drugs on development of local inflammation induced by injection of LNPF in rats was studied. The factor was obtained from guinea pig lymph nodes stimulated with Freund's complete adjuvant. The cell-free extract was obtained by disintegrating the cells, dialysis and lyophilization of the material. Preventive action of the drugs was dose-related. Strongest protection against the effect of LNPF was observed after administration of 6-MP and cyclophosphamide (100 mg/kh). Methotrexate (20 mg/kg) caused a reduction of the surface area of the inflammatory reaction by 70-90%, and 5-fluorouracil (50 mg/kg) by 35%-60%. Specific heterologous anti-LNPF serum was the most effective protective agent in rats; administered before the test, it prevented appearance of an inflammatory reaction altogether.", "contents": "Influence of immunosuppressive drugs on activity of lymph node permeability factor (LNPF). The influence of selected immunosuppressive drugs on development of local inflammation induced by injection of LNPF in rats was studied. The factor was obtained from guinea pig lymph nodes stimulated with Freund's complete adjuvant. The cell-free extract was obtained by disintegrating the cells, dialysis and lyophilization of the material. Preventive action of the drugs was dose-related. Strongest protection against the effect of LNPF was observed after administration of 6-MP and cyclophosphamide (100 mg/kh). Methotrexate (20 mg/kg) caused a reduction of the surface area of the inflammatory reaction by 70-90%, and 5-fluorouracil (50 mg/kg) by 35%-60%. Specific heterologous anti-LNPF serum was the most effective protective agent in rats; administered before the test, it prevented appearance of an inflammatory reaction altogether."} {"id": "PMID:1259533", "title": "Immunologic evaluation of beta-lipoprotein antigen in the serum of men exposed to carbon disulfide over protracted periods of time.", "content": "beta-Lipoprotein was isolated by the precipitation method from collective serum of 47 men aged 27-49 years (mean 42-1 years) exposed to carbon disulfide during work over long periods of time. Significantly elevated levels of serum beta-lipoprotein, clinical and polycardiographic symptoms were found in 85-1% of subjects. Antibodies to beta-lipoprotein obtained by immunizing rabbits intravenously were compared with similar antibodies in healthy subjects by double immunodiffusion in agar and by the passive hemagglutination test. Both tests showed identical antigens.", "contents": "Immunologic evaluation of beta-lipoprotein antigen in the serum of men exposed to carbon disulfide over protracted periods of time. beta-Lipoprotein was isolated by the precipitation method from collective serum of 47 men aged 27-49 years (mean 42-1 years) exposed to carbon disulfide during work over long periods of time. Significantly elevated levels of serum beta-lipoprotein, clinical and polycardiographic symptoms were found in 85-1% of subjects. Antibodies to beta-lipoprotein obtained by immunizing rabbits intravenously were compared with similar antibodies in healthy subjects by double immunodiffusion in agar and by the passive hemagglutination test. Both tests showed identical antigens."} {"id": "PMID:1259534", "title": "Morphologic homogeneity of bacteriophages and their biological activity.", "content": "Lytic activity of morphologically homogeneous phage lysates, obtained from lysates containing morphologically inhomogeneous virions, was studied. Five series of phage lysates found to contain morphologically inhomogeneous virions were investigated. By selecting suitable hosts from each series, two or three lines were obtained which reproduced morphologically homogeneous virions. Morphologic homogeneity of these phage lines was determined by electron microscopy. In the course of this study it was found that phages with different morphologic appearance can produce similar plaques. Hence, appearance of plaques is not an adequate criterion of homogeneity of the phage. The isolated phages differed in biological activity from the original morphologically inhomogeneous bacteriophage. It was concluded that morphology is an important, and the most reliable at present, criterion of homogeneity of bacteriophages.", "contents": "Morphologic homogeneity of bacteriophages and their biological activity. Lytic activity of morphologically homogeneous phage lysates, obtained from lysates containing morphologically inhomogeneous virions, was studied. Five series of phage lysates found to contain morphologically inhomogeneous virions were investigated. By selecting suitable hosts from each series, two or three lines were obtained which reproduced morphologically homogeneous virions. Morphologic homogeneity of these phage lines was determined by electron microscopy. In the course of this study it was found that phages with different morphologic appearance can produce similar plaques. Hence, appearance of plaques is not an adequate criterion of homogeneity of the phage. The isolated phages differed in biological activity from the original morphologically inhomogeneous bacteriophage. It was concluded that morphology is an important, and the most reliable at present, criterion of homogeneity of bacteriophages."} {"id": "PMID:1259535", "title": "The effect of gradual mild acid hydrolysis on serologic activities of glycoproteins from human erythrocytes.", "content": "M and N blood group glycoproteins from O group erythrocytes were hydrolyzed with acid under various conditions that produced a gradual release of sialic acid. The preparations desialized to different degree were tested for M, N, NVg and AHp activities. M and N blood group activity was decreased upon release of sialic acid, and AHp activity was exposed \"de novo\" and increased upon desialization. NVg activity always increased during the initial period of acid hydrolysis, but prolonged heating in acid solution caused subsequent partial inactivation of glycoprotein. This decrease in NHp activity was not related either to the extent of desialization, or to fragmentation of the glycoprotein molecule.", "contents": "The effect of gradual mild acid hydrolysis on serologic activities of glycoproteins from human erythrocytes. M and N blood group glycoproteins from O group erythrocytes were hydrolyzed with acid under various conditions that produced a gradual release of sialic acid. The preparations desialized to different degree were tested for M, N, NVg and AHp activities. M and N blood group activity was decreased upon release of sialic acid, and AHp activity was exposed \"de novo\" and increased upon desialization. NVg activity always increased during the initial period of acid hydrolysis, but prolonged heating in acid solution caused subsequent partial inactivation of glycoprotein. This decrease in NHp activity was not related either to the extent of desialization, or to fragmentation of the glycoprotein molecule."} {"id": "PMID:1259536", "title": "Molecular size and amino acid composition of H-2d antigen solubilized in Nonidet P-40.", "content": "H-2d antigenic material solubilized by the detergent Nonidet P-40 from L-1210 mouse leukemia cells was isolated by gel filtration on Bio-Gel P-100. A single peak eluted in the void volume consisted of about 90% protein, 8% hexose and traces of sialic acids. In sedimentation velocity runs, the antigen sedimented as a single peak of 3-1 S. Molecular weight determined by sedimentation equilibrium as well as calculated from amino acid composition was found to be in the range of 53,000 daltons and approx. 45,000-51,000 when calculated from sodium dodecyl sulfate polyacrylamide gel electrophoresis. Secondary structure of H-2d glycoprotein was predicted from the amino acid composition. For NP-40-solubilized H-2d antigen, about 34% of helix, 13% beta sheet and 41% turns was found.", "contents": "Molecular size and amino acid composition of H-2d antigen solubilized in Nonidet P-40. H-2d antigenic material solubilized by the detergent Nonidet P-40 from L-1210 mouse leukemia cells was isolated by gel filtration on Bio-Gel P-100. A single peak eluted in the void volume consisted of about 90% protein, 8% hexose and traces of sialic acids. In sedimentation velocity runs, the antigen sedimented as a single peak of 3-1 S. Molecular weight determined by sedimentation equilibrium as well as calculated from amino acid composition was found to be in the range of 53,000 daltons and approx. 45,000-51,000 when calculated from sodium dodecyl sulfate polyacrylamide gel electrophoresis. Secondary structure of H-2d glycoprotein was predicted from the amino acid composition. For NP-40-solubilized H-2d antigen, about 34% of helix, 13% beta sheet and 41% turns was found."} {"id": "PMID:1259537", "title": "Observations of absorption of immunolactoglobulins in calves.", "content": "The aim of this study was to ascertain whether administration of one liter of stilulated saliva from a healthy cow as first food to newborn calves blocks absorption of immunolactoglobulins administered later in colostrum or milk. The study material consisted of 12 calves, divided into two groups, one of which received colostrum, and the other milk. Blood samples were drawn immediately after birth and 3 and 6 hours after administration of saliva and 3 and 6 hours after administration of colostrum (group I) or milk (group II). Only some of the calves of each group absorbed immunolactoglobulins from colostrum or milk. In these calves, immunoglobulins could be demonstrated in their serum as early as 3 hours after birth. Absorption of immunolactoglobulins was independent of their concentration in food as their levels were similar in calves fed colostrum or milk. The experiment failed, however, to give an unequivocal answer to the question whether feeding calves before the first administration of colostrum restricts or inhibits absorption of immunolactoglobulins from colostrum.", "contents": "Observations of absorption of immunolactoglobulins in calves. The aim of this study was to ascertain whether administration of one liter of stilulated saliva from a healthy cow as first food to newborn calves blocks absorption of immunolactoglobulins administered later in colostrum or milk. The study material consisted of 12 calves, divided into two groups, one of which received colostrum, and the other milk. Blood samples were drawn immediately after birth and 3 and 6 hours after administration of saliva and 3 and 6 hours after administration of colostrum (group I) or milk (group II). Only some of the calves of each group absorbed immunolactoglobulins from colostrum or milk. In these calves, immunoglobulins could be demonstrated in their serum as early as 3 hours after birth. Absorption of immunolactoglobulins was independent of their concentration in food as their levels were similar in calves fed colostrum or milk. The experiment failed, however, to give an unequivocal answer to the question whether feeding calves before the first administration of colostrum restricts or inhibits absorption of immunolactoglobulins from colostrum."} {"id": "PMID:1259538", "title": "Evaluation of measurements of infectious titers of the vaccinia virus in passaged human embryonic fibroblasts.", "content": "Measurements of infectivity of the vaccinia virus on 11 cell lines derived from human embryos and passaged several times were analyzed statistically. Various cell lines showed different sensitivity and differentiated response in various passages.", "contents": "Evaluation of measurements of infectious titers of the vaccinia virus in passaged human embryonic fibroblasts. Measurements of infectivity of the vaccinia virus on 11 cell lines derived from human embryos and passaged several times were analyzed statistically. Various cell lines showed different sensitivity and differentiated response in various passages."} {"id": "PMID:1259539", "title": "Concerning cellular defense in carcinoma of the larynx.", "content": "In the search of microscopic manifestations of cellular defense in tumor disease, larynx specimens removed surgically for carcinoma of the larynx and neighboring lymph nodes were studied morphologically. Blastic transformation of lymphocytes from the lymph nodes was also investigated. Activity of nuclear chromatin of these cells was assessed on the basis of its sensitivity to acid hydrolysis in the reaction of Feulgen and incorporation of labeled 3H-actinomycin D. The results indicate existence of cellular defense reaction in carcinoma of the larynx, around the primary tumor as well as in neighboring lymph nodes. Intensity of the reaction in lymph nodes increases with growth of the primary tumor.", "contents": "Concerning cellular defense in carcinoma of the larynx. In the search of microscopic manifestations of cellular defense in tumor disease, larynx specimens removed surgically for carcinoma of the larynx and neighboring lymph nodes were studied morphologically. Blastic transformation of lymphocytes from the lymph nodes was also investigated. Activity of nuclear chromatin of these cells was assessed on the basis of its sensitivity to acid hydrolysis in the reaction of Feulgen and incorporation of labeled 3H-actinomycin D. The results indicate existence of cellular defense reaction in carcinoma of the larynx, around the primary tumor as well as in neighboring lymph nodes. Intensity of the reaction in lymph nodes increases with growth of the primary tumor."} {"id": "PMID:1259540", "title": "In vitro response of lymphocytes to phytohemagglutinin (PHA) and serum levels of immunoglobulins during remission of acute leukemia.", "content": "The study group consisted of 13 patients, including 5 in complete remission and 8 in incomplete hematologic remission. Six patients had a pause in therapy, and the remaining ones were continuing maintenance therapy. In all cases production of IgG, IgA and IgM immunoglobulins was maintained. Response of lymphocytes to PHA in vitro was normal in 7 patients, mainly in those who had a pause in treatment. The test results were uncorrelated with hematologic status. Both tests showed preserved humoral immunity and delyed hypersensitivity in the early period of remission and had no prognositc value.", "contents": "In vitro response of lymphocytes to phytohemagglutinin (PHA) and serum levels of immunoglobulins during remission of acute leukemia. The study group consisted of 13 patients, including 5 in complete remission and 8 in incomplete hematologic remission. Six patients had a pause in therapy, and the remaining ones were continuing maintenance therapy. In all cases production of IgG, IgA and IgM immunoglobulins was maintained. Response of lymphocytes to PHA in vitro was normal in 7 patients, mainly in those who had a pause in treatment. The test results were uncorrelated with hematologic status. Both tests showed preserved humoral immunity and delyed hypersensitivity in the early period of remission and had no prognositc value."} {"id": "PMID:1259541", "title": "Stimulation of blastic transformation of rabbit lymphocytes by means of endotoxins of Bacteroides fragilis.", "content": "Blastic transformation of lymphocytes from peripheral blood of rabbits immunized with formolized suspensions of Bacteroides fragilis was obtained. Stimulation was accomplished by means of endotoxins extracted from the strain with which the animals were immunized, and from a related serotype. Blastic transformation was obtained 21 days after the start of immunization of the animals, and maximum response after 4-5 weeks. Humoral response, checked by the passive hemagglutination test, preceded cellular response by 14 days.", "contents": "Stimulation of blastic transformation of rabbit lymphocytes by means of endotoxins of Bacteroides fragilis. Blastic transformation of lymphocytes from peripheral blood of rabbits immunized with formolized suspensions of Bacteroides fragilis was obtained. Stimulation was accomplished by means of endotoxins extracted from the strain with which the animals were immunized, and from a related serotype. Blastic transformation was obtained 21 days after the start of immunization of the animals, and maximum response after 4-5 weeks. Humoral response, checked by the passive hemagglutination test, preceded cellular response by 14 days."} {"id": "PMID:1259543", "title": "EMG feedback therapy: review of treatment of 114 patients.", "content": "Advances in the understanding of the relationship of proprioceptive (kinesthetic) feedback to motor physiology have prompted the study of therapeutic effects of audiovisual displays of EMG activity. Patients with various manifestations of disturbed neuromotor control were studied prospectively for three years. This group included 114 patients with hemiparesis, torticollis, dystonia, and spinal cord or peripheral nerve injury. Initially, all but one of these patients had some residual volitional motor activity, which was insufficient for adequate function, and all patients had had conventional therapy with little or no functional recovery. Prior to EMG feedback therapy, the duration of illness was from three months to 35 years. The shaping of a patient's motor responses usually occurred gradually, often over an 8 to 12 week period. This modification was accomplished by feeding processed audio-visual signals back to the patient. These signals were proportional to the degree of activity of the muscles responsible for the defective function. The concept of microvolt-second, as a unit of muscle activity, is introduced and defined. Patterned movements, which were previously defective were observed to improve to varying degrees. Following the initial course of treatment, reinforcement was required by some patients. The mechanisms of improvement after EMG feeback therapy are not well understood; however, some hypotheses are presented. The results of this study indicate that EMG feedback therapy may induce significant functional recovery in patients with disturbed neuromotor control.", "contents": "EMG feedback therapy: review of treatment of 114 patients. Advances in the understanding of the relationship of proprioceptive (kinesthetic) feedback to motor physiology have prompted the study of therapeutic effects of audiovisual displays of EMG activity. Patients with various manifestations of disturbed neuromotor control were studied prospectively for three years. This group included 114 patients with hemiparesis, torticollis, dystonia, and spinal cord or peripheral nerve injury. Initially, all but one of these patients had some residual volitional motor activity, which was insufficient for adequate function, and all patients had had conventional therapy with little or no functional recovery. Prior to EMG feedback therapy, the duration of illness was from three months to 35 years. The shaping of a patient's motor responses usually occurred gradually, often over an 8 to 12 week period. This modification was accomplished by feeding processed audio-visual signals back to the patient. These signals were proportional to the degree of activity of the muscles responsible for the defective function. The concept of microvolt-second, as a unit of muscle activity, is introduced and defined. Patterned movements, which were previously defective were observed to improve to varying degrees. Following the initial course of treatment, reinforcement was required by some patients. The mechanisms of improvement after EMG feeback therapy are not well understood; however, some hypotheses are presented. The results of this study indicate that EMG feedback therapy may induce significant functional recovery in patients with disturbed neuromotor control."} {"id": "PMID:1259544", "title": "Electrodiagnostic evidence of subclinical disease states in drug abusers.", "content": "One hundred drug abusers, free of clinical signs or symptoms of disease, were examined by electrodiagnostic techniques. Sensory conduction of median, ulnar and sural nerves was evaluated in terms of latency, velocity and amplitude of evoked potential. Motor nerve latencies and conduction velocities of median, ulnar and personeal nerves were determined. Definite changes in the evoked sensory potentials of median and sural nerves of subjects using heroin or LSD were demonstrated. The sensory amplitude changes were suggestive of axonal degreneration because of normal duration. Maximum motor conduction velocity was abnormal in one patient who admitted using a variety of drugs; five heroin and two barbiturate users showed dispersed motor responses suggesting small fiber involvement. No abnormality could be shown in marjuana smokers. Signifcance of these findings is explained, emphasizing important potential for recognition of subclinical abnormalities and the opportunity for disease prevention.", "contents": "Electrodiagnostic evidence of subclinical disease states in drug abusers. One hundred drug abusers, free of clinical signs or symptoms of disease, were examined by electrodiagnostic techniques. Sensory conduction of median, ulnar and sural nerves was evaluated in terms of latency, velocity and amplitude of evoked potential. Motor nerve latencies and conduction velocities of median, ulnar and personeal nerves were determined. Definite changes in the evoked sensory potentials of median and sural nerves of subjects using heroin or LSD were demonstrated. The sensory amplitude changes were suggestive of axonal degreneration because of normal duration. Maximum motor conduction velocity was abnormal in one patient who admitted using a variety of drugs; five heroin and two barbiturate users showed dispersed motor responses suggesting small fiber involvement. No abnormality could be shown in marjuana smokers. Signifcance of these findings is explained, emphasizing important potential for recognition of subclinical abnormalities and the opportunity for disease prevention."} {"id": "PMID:1259545", "title": "Clinical electromyography of the hand.", "content": "The anatomically oriented electromyographer has much to offer in the solution of clinical problems relating to dysfunctional states of the hand. Because of the frequency of variations in innervation, it is often necessary to examine more of the specific intrinsic muscles than is customary. To do this with confidence, a practical method of electrode placement and localization is necessary. The technique described is offered as such a method.", "contents": "Clinical electromyography of the hand. The anatomically oriented electromyographer has much to offer in the solution of clinical problems relating to dysfunctional states of the hand. Because of the frequency of variations in innervation, it is often necessary to examine more of the specific intrinsic muscles than is customary. To do this with confidence, a practical method of electrode placement and localization is necessary. The technique described is offered as such a method."} {"id": "PMID:1259546", "title": "Electrophysiological studies in the assessment of spinal cord lesions.", "content": "Electromyography is a valuable tool in the diagnosis of neuromuscular disorders. In this study, detailed electrophysiological studies were performed on all recent traumatic quadriplegic and paraplegic patients admitted to a spinal cord unit. The data obtained supplemented the clinical information in the assessment of individual patients. Certain patterns of abnormalities emerged, and attempts were made to relate these patterns to the pathology of the various lesions.", "contents": "Electrophysiological studies in the assessment of spinal cord lesions. Electromyography is a valuable tool in the diagnosis of neuromuscular disorders. In this study, detailed electrophysiological studies were performed on all recent traumatic quadriplegic and paraplegic patients admitted to a spinal cord unit. The data obtained supplemented the clinical information in the assessment of individual patients. Certain patterns of abnormalities emerged, and attempts were made to relate these patterns to the pathology of the various lesions."} {"id": "PMID:1259547", "title": "Acetylcholinesterase in abnormal human muscle.", "content": "Fifty human muscle biopsies were examined for histochemical localization of acetylcholinesterase (AChE) activity. Six normal muscle samples had AChE at the myoneural junctions and around the periphery of many fibers. The AChE within the sarcoplasm itself was found in only a few atrophied fibers. However, 21 of 44 biopsies of abnormal muscles had sarcoplasmic AChE in more than 10% of their fibers. Such cases included Duchenne, limb-girdle and facio-scapulo-humeral dystrophy, neurogenic and spinal muscle atrophy, spinal cord injury, peripheral nerve injury, Schwartz-Jampel syndrome and myasthenic syndrome. Sarcoplasmic AChE is found in embryo muscle and usually declines after birth. It appears after denervation in the chicken but not the rat and remains in muscles of chickens with an inherited muscular dystrophy. The results of the human muscle study support the idea that in the human, as in the chicken, interruption of a neurally-mediated regulation of AChE results in the reappearance of high AChE activity in the sarcoplasm of the muscle fibers.", "contents": "Acetylcholinesterase in abnormal human muscle. Fifty human muscle biopsies were examined for histochemical localization of acetylcholinesterase (AChE) activity. Six normal muscle samples had AChE at the myoneural junctions and around the periphery of many fibers. The AChE within the sarcoplasm itself was found in only a few atrophied fibers. However, 21 of 44 biopsies of abnormal muscles had sarcoplasmic AChE in more than 10% of their fibers. Such cases included Duchenne, limb-girdle and facio-scapulo-humeral dystrophy, neurogenic and spinal muscle atrophy, spinal cord injury, peripheral nerve injury, Schwartz-Jampel syndrome and myasthenic syndrome. Sarcoplasmic AChE is found in embryo muscle and usually declines after birth. It appears after denervation in the chicken but not the rat and remains in muscles of chickens with an inherited muscular dystrophy. The results of the human muscle study support the idea that in the human, as in the chicken, interruption of a neurally-mediated regulation of AChE results in the reappearance of high AChE activity in the sarcoplasm of the muscle fibers."} {"id": "PMID:1259549", "title": "Electromyographic findings in the extensor digitorum brevis in a normal population.", "content": "Some electromyographers suggest the diagnosis of radiculopathy when electromyographic examination reveals abnormalities in only one muscle, the extensor digitorum brevis. We studied 70 volunteers free of neuromuscular disease and found electromyographic abnormalities in 11. We conclude that abnormal electrical activities found solely in the extensor digitorum brevis may not be diagnostically signifcant for lumbosacral radiculopathy.", "contents": "Electromyographic findings in the extensor digitorum brevis in a normal population. Some electromyographers suggest the diagnosis of radiculopathy when electromyographic examination reveals abnormalities in only one muscle, the extensor digitorum brevis. We studied 70 volunteers free of neuromuscular disease and found electromyographic abnormalities in 11. We conclude that abnormal electrical activities found solely in the extensor digitorum brevis may not be diagnostically signifcant for lumbosacral radiculopathy."} {"id": "PMID:1259550", "title": "Brothel prostitution in Columbia.", "content": "Peculiarities of Colombian brothel prostitution as well as its similarities to that practiced elsewhere are reported. Data gathered through interviews with a group of brothel residents in Manizales, and by means of participant observations in the brothels of several Colombian cities, indicate that economic factors play an important role in its etiology and maintenance. Incomplete \"commercialization\" of this prostitution system is described along with the negligible role played by pimps and the freedom Colombian prostitutes have to dispose of their earnings. Misconceptions about prostitutes pointed out by other authors (Pomeroy, 1965; Gebhard, 1969), such as marked infertility, irreligiousness, and homosexuality, are also contested by this study. Pomeroy's and Gebhard's findings of the prostitute's lack of regret about her trade are not confirmed. It is the authors' contention that prostitution shows ample sociocultural variations and that theoretical generalizations regarding it do not apply to different cultural milieus.", "contents": "Brothel prostitution in Columbia. Peculiarities of Colombian brothel prostitution as well as its similarities to that practiced elsewhere are reported. Data gathered through interviews with a group of brothel residents in Manizales, and by means of participant observations in the brothels of several Colombian cities, indicate that economic factors play an important role in its etiology and maintenance. Incomplete \"commercialization\" of this prostitution system is described along with the negligible role played by pimps and the freedom Colombian prostitutes have to dispose of their earnings. Misconceptions about prostitutes pointed out by other authors (Pomeroy, 1965; Gebhard, 1969), such as marked infertility, irreligiousness, and homosexuality, are also contested by this study. Pomeroy's and Gebhard's findings of the prostitute's lack of regret about her trade are not confirmed. It is the authors' contention that prostitution shows ample sociocultural variations and that theoretical generalizations regarding it do not apply to different cultural milieus."} {"id": "PMID:1259551", "title": "Male homosexuality, psychiatric patient status, and psychological masculinity and femininity.", "content": "The personality dynamics of homosexuality, psychiatric patient status, and psychological masculinity and femininity were assessed for four groups of 45 male subjects in a full factorial comparison. Results show that homosexuality can be significantly characterized by the Dynamic Personality Inventory independently of psychiatric attendance and that aspects of sex role, considered both normatively and within the sample, are especially effective in that respect. Emphasis is laid on a multidimensional approach to masculinity and femininity. Results are further interpreted with regard to parental relations and the minority status of male homosexuals.", "contents": "Male homosexuality, psychiatric patient status, and psychological masculinity and femininity. The personality dynamics of homosexuality, psychiatric patient status, and psychological masculinity and femininity were assessed for four groups of 45 male subjects in a full factorial comparison. Results show that homosexuality can be significantly characterized by the Dynamic Personality Inventory independently of psychiatric attendance and that aspects of sex role, considered both normatively and within the sample, are especially effective in that respect. Emphasis is laid on a multidimensional approach to masculinity and femininity. Results are further interpreted with regard to parental relations and the minority status of male homosexuals."} {"id": "PMID:1259552", "title": "Premarital sexual attitudes of unmarried university students: 1968 vs. 1972.", "content": "Information on premarital sexual attitudes of unmarried undergraduates was obtained from random samples on the same campus in 1968 and 1972. Students in 1972, compared with those in 1968, reported (1) more permissive attitudes toward premarital sexual behavior (both men and women), (2) fewer differences in attitudes between men and women, and (3) less adherence to the \"double standard.\" In contrast to earlier research on premarital sexual attitudes, these differences need not be due to the markedly different populations compared, or generalizable only to sociology and psychology students, or indicative of only those who chose to volunteer for study (volunteer bias).", "contents": "Premarital sexual attitudes of unmarried university students: 1968 vs. 1972. Information on premarital sexual attitudes of unmarried undergraduates was obtained from random samples on the same campus in 1968 and 1972. Students in 1972, compared with those in 1968, reported (1) more permissive attitudes toward premarital sexual behavior (both men and women), (2) fewer differences in attitudes between men and women, and (3) less adherence to the \"double standard.\" In contrast to earlier research on premarital sexual attitudes, these differences need not be due to the markedly different populations compared, or generalizable only to sociology and psychology students, or indicative of only those who chose to volunteer for study (volunteer bias)."} {"id": "PMID:1259553", "title": "Formal and informal sex education as determinants of premarital sexual behavior.", "content": "Controversies exist regarding the effects of sex education in the schools and informal sex education obtained from parents, peers, the mass media, and other sources. Similarly, there is widespread interest in premarital sexual behavior, especially its determinants. This study presents several issues reflecting these concerns which have been the subject of much speculation but which have received little attention by researchers. The purpose of this study was to investigate--through the use of respondent reports--how formal and informal sex education influences premarital sexual behavior during college. A national probability sample of 1177 college students was studied using face-to-face interviews with approximately equal numbers of males and females. These interviews, which were conducted for the Institute for Sex Research, included questions about past and present sexual involvement and other attitudinal, behavioral and background variables. Accordingly, the data about sexual behavior and attitudes are based on the interviewees' self-reports. Indices were created which operationalized independent variables such as familial sexual conservatism, exposure to eroticism, perceived sex knowledge, and sexual exposure and assault during childhood and adolescence. Individual items reflecting childhood sex play, masturbation, current religiosity, religiosity while growing up, social class, sources of sex information, sex education in classrooms, and high school and college dating were used. The dependent variable, premarital sociosexual involvement, is a composite measure of incidence and prevalence of premarital heterosexual involvement which meets Guttman scaling criteria. An Automatic Interaction Detector analysis was used to determine the relative influences of reported sexualization variables on premarital sexual behavior. Major findings can be summarized as follows: Heterosexual behavior progresses in stepwise fashion from elementary to advanced levels of involvement, with each level representing a threshold. Reports of current influences and pressures explain more variance in premarital sexual behavior than reports of past informal sexualization influences, which, in turn, explain more variance than reported formal sex-education experiences. Limited success was reported with the use of a four-stage AID analysis which attempted to ascertain whether variables represented in later stages of the sexualization process \"mask\" the effects of variables in earlier stages and whether a development process can be identified. It may be concluded that these data do not support the belief that exposure to sexuality through formal sex education influences premarital sexual behavior. Informal sex education has significantly more impact on premarital sexual behavior, but there are indications that pressures and experiences confronting young people in a given dating or peer group situation take precedence over all past sexual socialization influences.", "contents": "Formal and informal sex education as determinants of premarital sexual behavior. Controversies exist regarding the effects of sex education in the schools and informal sex education obtained from parents, peers, the mass media, and other sources. Similarly, there is widespread interest in premarital sexual behavior, especially its determinants. This study presents several issues reflecting these concerns which have been the subject of much speculation but which have received little attention by researchers. The purpose of this study was to investigate--through the use of respondent reports--how formal and informal sex education influences premarital sexual behavior during college. A national probability sample of 1177 college students was studied using face-to-face interviews with approximately equal numbers of males and females. These interviews, which were conducted for the Institute for Sex Research, included questions about past and present sexual involvement and other attitudinal, behavioral and background variables. Accordingly, the data about sexual behavior and attitudes are based on the interviewees' self-reports. Indices were created which operationalized independent variables such as familial sexual conservatism, exposure to eroticism, perceived sex knowledge, and sexual exposure and assault during childhood and adolescence. Individual items reflecting childhood sex play, masturbation, current religiosity, religiosity while growing up, social class, sources of sex information, sex education in classrooms, and high school and college dating were used. The dependent variable, premarital sociosexual involvement, is a composite measure of incidence and prevalence of premarital heterosexual involvement which meets Guttman scaling criteria. An Automatic Interaction Detector analysis was used to determine the relative influences of reported sexualization variables on premarital sexual behavior. Major findings can be summarized as follows: Heterosexual behavior progresses in stepwise fashion from elementary to advanced levels of involvement, with each level representing a threshold. Reports of current influences and pressures explain more variance in premarital sexual behavior than reports of past informal sexualization influences, which, in turn, explain more variance than reported formal sex-education experiences. Limited success was reported with the use of a four-stage AID analysis which attempted to ascertain whether variables represented in later stages of the sexualization process \"mask\" the effects of variables in earlier stages and whether a development process can be identified. It may be concluded that these data do not support the belief that exposure to sexuality through formal sex education influences premarital sexual behavior. Informal sex education has significantly more impact on premarital sexual behavior, but there are indications that pressures and experiences confronting young people in a given dating or peer group situation take precedence over all past sexual socialization influences."} {"id": "PMID:1259554", "title": "Mother-father and daughter-male relationships: a comparison.", "content": "A two-generation study of pregnant nulliparous women (daughters) and their mothers is presented. The women in both generations were interviewed. Daughters from homes characterized by marital discord between the parents (as judged from the report of the mother) were compared to daughters from harmonious homes. Daughters from discordant homes reported a poor emotional relationship with their father. In contrast, the emotional relationship with the mother was little influenced by parental discord. Daughters from discordant homes reported less stable and gratifying relationships with male partners and more sex partners than daughters from harmonious homes. At the time of their first pregnancy, daughters from discordant homes received little support from the father of the child. They more often described unsatisfactory housing and financial conditions. Poor parental interralations may impair the daughter's ability to establish gratifying relationships with men. One explanation is the daughter's identification with her parents. During the identification process, the daughter of discordant parents assimilates her parents' negative patterns of relating to each other. These unsuccessful patterns may later undermine her ability to establish positive relationships with men.", "contents": "Mother-father and daughter-male relationships: a comparison. A two-generation study of pregnant nulliparous women (daughters) and their mothers is presented. The women in both generations were interviewed. Daughters from homes characterized by marital discord between the parents (as judged from the report of the mother) were compared to daughters from harmonious homes. Daughters from discordant homes reported a poor emotional relationship with their father. In contrast, the emotional relationship with the mother was little influenced by parental discord. Daughters from discordant homes reported less stable and gratifying relationships with male partners and more sex partners than daughters from harmonious homes. At the time of their first pregnancy, daughters from discordant homes received little support from the father of the child. They more often described unsatisfactory housing and financial conditions. Poor parental interralations may impair the daughter's ability to establish gratifying relationships with men. One explanation is the daughter's identification with her parents. During the identification process, the daughter of discordant parents assimilates her parents' negative patterns of relating to each other. These unsuccessful patterns may later undermine her ability to establish positive relationships with men."} {"id": "PMID:1259555", "title": "Behavioral differences and emotional conflict among male-to-female transsexuals.", "content": "Salient differences in behavior between two groups of male transsexuals have been studied. Topics investigated are transsexualism and homosexuality, prostitution and employment, affectlessness, need for reassurance, and deprecation of others. The hypothesis is advanced that those who are leading more stable lives and who are working in gainful employment have developed a stronger self-system which has enabled them to come to terms more effectively with the basic emotional conflict underlying transsexualism than have those who are and have been engaged in homosexuality and prostitution.", "contents": "Behavioral differences and emotional conflict among male-to-female transsexuals. Salient differences in behavior between two groups of male transsexuals have been studied. Topics investigated are transsexualism and homosexuality, prostitution and employment, affectlessness, need for reassurance, and deprecation of others. The hypothesis is advanced that those who are leading more stable lives and who are working in gainful employment have developed a stronger self-system which has enabled them to come to terms more effectively with the basic emotional conflict underlying transsexualism than have those who are and have been engaged in homosexuality and prostitution."} {"id": "PMID:1259556", "title": "Written descriptions of orgasm: a study of sex differences.", "content": "It has generally been assumed that a male's experience of orgasm is different from a female's experience of orgasm. In this study, a questionnaire consisting of 48 description of orgasm (24 male and 24 female) was submitted to 70 judges. These professionals (obstetrician-gynecologists, psychologists and medical students) were to sex-identify the description to discover whether sex differences could be detected. The judges could not correctly identify the sex of the person describing an orgasm. Furthermore, none of the three professional groups represented in the sample of judges did better than any of the other groups. Male judges did no better than female judges and vice versa. These findings suggest that the experience of orgasm for males and females is essentially the same.", "contents": "Written descriptions of orgasm: a study of sex differences. It has generally been assumed that a male's experience of orgasm is different from a female's experience of orgasm. In this study, a questionnaire consisting of 48 description of orgasm (24 male and 24 female) was submitted to 70 judges. These professionals (obstetrician-gynecologists, psychologists and medical students) were to sex-identify the description to discover whether sex differences could be detected. The judges could not correctly identify the sex of the person describing an orgasm. Furthermore, none of the three professional groups represented in the sample of judges did better than any of the other groups. Male judges did no better than female judges and vice versa. These findings suggest that the experience of orgasm for males and females is essentially the same."} {"id": "PMID:1259559", "title": "Tibial artery bypass.", "content": "Experience with 29 tibial bypasses is presented. Twenty-one have remained patent for an average time of 13.2 months. There were two hospital deaths and five additional late ones. Autogenous saphenous vein was used in 27. Electromagnetic flowmeter studies were useful in assessment of patency, but intraoperative arteriography was of limited value only. The use of peroneal artery had equivalent results to anterior and posterior tibial arteries. It is concluded that a reasonable limb prognosis may be offered to the patient with advanced ischemic disease and one or more open tibial vessels. The late mortality in this group is appreciable.", "contents": "Tibial artery bypass. Experience with 29 tibial bypasses is presented. Twenty-one have remained patent for an average time of 13.2 months. There were two hospital deaths and five additional late ones. Autogenous saphenous vein was used in 27. Electromagnetic flowmeter studies were useful in assessment of patency, but intraoperative arteriography was of limited value only. The use of peroneal artery had equivalent results to anterior and posterior tibial arteries. It is concluded that a reasonable limb prognosis may be offered to the patient with advanced ischemic disease and one or more open tibial vessels. The late mortality in this group is appreciable."} {"id": "PMID:1259560", "title": "Gastric acid secretion and acute gastroduodenal disease after burns.", "content": "Total titratable acidity of fasting gastric secretion was determined in 34 hemodynamically stable patients within five days after burn. Acid output was not predictive of disease; acute duodenal ulcers, however, were not discovered in patients with acid secretion of less than 3.11 mEq/hr. Patients with both gastric and duodenal disease secreted significantly (P less than .05) more acid than patients without duodenal involvement and complications were more likely to develop, especially from acute ulcerations. Hemorrhage or perforation occurred in nine patients whose acid output was significantly (P less than .05) greater than that of asymptomatic patients. Duodenal regulation and neutralization of acid secretion may be impaired in patients with early duodenal injury, resulting in a relative increase in acid output and enhanced potential for complications. A controlled evaluation of antacid therapy in the prevention of disease complications seems justified in these patients.", "contents": "Gastric acid secretion and acute gastroduodenal disease after burns. Total titratable acidity of fasting gastric secretion was determined in 34 hemodynamically stable patients within five days after burn. Acid output was not predictive of disease; acute duodenal ulcers, however, were not discovered in patients with acid secretion of less than 3.11 mEq/hr. Patients with both gastric and duodenal disease secreted significantly (P less than .05) more acid than patients without duodenal involvement and complications were more likely to develop, especially from acute ulcerations. Hemorrhage or perforation occurred in nine patients whose acid output was significantly (P less than .05) greater than that of asymptomatic patients. Duodenal regulation and neutralization of acid secretion may be impaired in patients with early duodenal injury, resulting in a relative increase in acid output and enhanced potential for complications. A controlled evaluation of antacid therapy in the prevention of disease complications seems justified in these patients."} {"id": "PMID:1259561", "title": "Canine small bowel transplantation. A study of the immunological responses.", "content": "A canine small bowel allograft model was used to determine the effects of radiation to the graft in modifying the immunological effects of the passenger leukocytes. When untreated allografts were transplanted, death of the recipient animals occurred at a mean of nine days. The allograft was well-preserved and showed no signs of rejection. The reasons for attributing death to graft-versus-host (GVH) disease are discussed. When allografts were treated with 150 rads prior to transplantation, allograft rejection occurred, with death of the recipient animals at a mean of 9.2 days. This was the only group in which cell-mediated immunity developed. When allografts were treated with 50 rads, prolonged survival of the recipients to a mean of 28 days was noted. It is postulated that in this group a balance was struck between the allograft rejection reaction and GVH disease, with prolongation of allograft survival.", "contents": "Canine small bowel transplantation. A study of the immunological responses. A canine small bowel allograft model was used to determine the effects of radiation to the graft in modifying the immunological effects of the passenger leukocytes. When untreated allografts were transplanted, death of the recipient animals occurred at a mean of nine days. The allograft was well-preserved and showed no signs of rejection. The reasons for attributing death to graft-versus-host (GVH) disease are discussed. When allografts were treated with 150 rads prior to transplantation, allograft rejection occurred, with death of the recipient animals at a mean of 9.2 days. This was the only group in which cell-mediated immunity developed. When allografts were treated with 50 rads, prolonged survival of the recipients to a mean of 28 days was noted. It is postulated that in this group a balance was struck between the allograft rejection reaction and GVH disease, with prolongation of allograft survival."} {"id": "PMID:1259562", "title": "Preservation of canine small bowel by freezing.", "content": "A total of 133 canine small bowel segments were isolated in 51 dogs according to a previously described technique that permits an in vivo freeze-thaw experiment to be carried out after perfusion with various cryoprotective agents. All control segments (33) survived. One hundred segments were frozen with cold intra-arterial helium and ambient cold nitrogen gas after perfusion with dimethyl sulfoxide (DMSO), inositol, or glycerol in 5% and 10% concentrations, alone, or combined, and with chlorpromazine and hydrocortisone added. Inositol had no cryoprotective effect. Approximately one half of segments frozen after protection with DMSO and with glycerol alone or combined with inositol survived the freeze-thaw injury and were intact on long-term follow-up.", "contents": "Preservation of canine small bowel by freezing. A total of 133 canine small bowel segments were isolated in 51 dogs according to a previously described technique that permits an in vivo freeze-thaw experiment to be carried out after perfusion with various cryoprotective agents. All control segments (33) survived. One hundred segments were frozen with cold intra-arterial helium and ambient cold nitrogen gas after perfusion with dimethyl sulfoxide (DMSO), inositol, or glycerol in 5% and 10% concentrations, alone, or combined, and with chlorpromazine and hydrocortisone added. Inositol had no cryoprotective effect. Approximately one half of segments frozen after protection with DMSO and with glycerol alone or combined with inositol survived the freeze-thaw injury and were intact on long-term follow-up."} {"id": "PMID:1259563", "title": "Small vessel replacement with gore-tex (expanded polytetrafluoroethylene).", "content": "Conduits of expanded, fibrillated polytetrafluoroethylene (PTFE [Gore-tex]) have been evaluated as small vessel prostheses in dogs during a 6-month period. A configuration of high porosity and low density, long fibril Gore-tex was found to yield the best patency in canine arteries (femoral and carotid) and veins (femoral) as compared with more dense, less porous PTFE with shorter fibrils. Host tissue reaction showed minimal inflammation, excellent infiltration, and formation of a smooth neointima, which suggested satisfactory acceptance of the prosthesis.", "contents": "Small vessel replacement with gore-tex (expanded polytetrafluoroethylene). Conduits of expanded, fibrillated polytetrafluoroethylene (PTFE [Gore-tex]) have been evaluated as small vessel prostheses in dogs during a 6-month period. A configuration of high porosity and low density, long fibril Gore-tex was found to yield the best patency in canine arteries (femoral and carotid) and veins (femoral) as compared with more dense, less porous PTFE with shorter fibrils. Host tissue reaction showed minimal inflammation, excellent infiltration, and formation of a smooth neointima, which suggested satisfactory acceptance of the prosthesis."} {"id": "PMID:1259564", "title": "Spontaneous perforation of the cervical esophagus.", "content": "A rare case of spontaneous rupture of the cervical esophagus occurred during vomiting after eating. The plain x-ray film showed air in the neck, but barium swallow did not reveal the perforation. Operation performed two days later because of bleeding consisted of suturing two rents in the anterior wall of the cervical esophagus distal to the cricopharyngeus muscle, and the patient did well. The mechanism causing such a perforation is not well understood. With the absence of bleeding, treatment would ordinarily consist of drainage without suture.", "contents": "Spontaneous perforation of the cervical esophagus. A rare case of spontaneous rupture of the cervical esophagus occurred during vomiting after eating. The plain x-ray film showed air in the neck, but barium swallow did not reveal the perforation. Operation performed two days later because of bleeding consisted of suturing two rents in the anterior wall of the cervical esophagus distal to the cricopharyngeus muscle, and the patient did well. The mechanism causing such a perforation is not well understood. With the absence of bleeding, treatment would ordinarily consist of drainage without suture."} {"id": "PMID:1259565", "title": "Crossed double internal mammary-to-coronary artery grafts.", "content": "Crossed double internal mammary (IMA)-coronary artery grafts (the left to the left anterior descending artery [LAD], the right to a diagonal or marginal coronary branch) were used without mortality and with excellent functional results in 36 patients requiring separate grafts to these vessels (22% of patients undergoing coronary revascularization). Flows were 70 +/- 9 ml/min in the left and 50 +/- 7 ml/min in the right IMA, respectively. All revisualized grafts remained patient. The location and direction of the LAD and of diagonal and marginal branches allow excellent alignment of these shorter and wider double IMA grafts. The left IMA is the graft of choice for the LAD, and the right IMA is the choice for a high diagonal or early arising marginal branch that requires an additional separate graft. The right IMA is not satisfactory for right coronary or LAD bypass.", "contents": "Crossed double internal mammary-to-coronary artery grafts. Crossed double internal mammary (IMA)-coronary artery grafts (the left to the left anterior descending artery [LAD], the right to a diagonal or marginal coronary branch) were used without mortality and with excellent functional results in 36 patients requiring separate grafts to these vessels (22% of patients undergoing coronary revascularization). Flows were 70 +/- 9 ml/min in the left and 50 +/- 7 ml/min in the right IMA, respectively. All revisualized grafts remained patient. The location and direction of the LAD and of diagonal and marginal branches allow excellent alignment of these shorter and wider double IMA grafts. The left IMA is the graft of choice for the LAD, and the right IMA is the choice for a high diagonal or early arising marginal branch that requires an additional separate graft. The right IMA is not satisfactory for right coronary or LAD bypass."} {"id": "PMID:1259566", "title": "Endoscopic removal of bleeding brunner gland adenoma.", "content": "A 36-year-old man had a major hematemesis because of a Brunner gland adenoma in the postbulbar portion of the duodenum. Three months later, the adenoma was successfully removed electively via endoscopic polypectomy. This is the first patient reported, to our knowledge, to have this technique for a bleeding Brunner gland adenoma. Endoscopic surgery is a relatively new development, and the technique of polypectomy has been used primarily in the colon. Surgery via upper gastrointestinal endoscopy promises to be as useful, although a somewhat different set of precautions applies.", "contents": "Endoscopic removal of bleeding brunner gland adenoma. A 36-year-old man had a major hematemesis because of a Brunner gland adenoma in the postbulbar portion of the duodenum. Three months later, the adenoma was successfully removed electively via endoscopic polypectomy. This is the first patient reported, to our knowledge, to have this technique for a bleeding Brunner gland adenoma. Endoscopic surgery is a relatively new development, and the technique of polypectomy has been used primarily in the colon. Surgery via upper gastrointestinal endoscopy promises to be as useful, although a somewhat different set of precautions applies."} {"id": "PMID:1259567", "title": "An experience with a LeVeen ascites shunt.", "content": "A patient with intractable ascites was treated by placement of the LeVeen peritoneovenous shunt. Shunt failure was caused by malpositioning of the venous limb in the inferior vena cava. This was demonstrated by injection of water-soluble contrast material into the venous limb. Revision of the shunt led to diuresis, weight loss, and reduction of ascites. The physiologic process of the LeVeen shunt is reviewed and we suggest placement of a radiopaque marker into the tubing.", "contents": "An experience with a LeVeen ascites shunt. A patient with intractable ascites was treated by placement of the LeVeen peritoneovenous shunt. Shunt failure was caused by malpositioning of the venous limb in the inferior vena cava. This was demonstrated by injection of water-soluble contrast material into the venous limb. Revision of the shunt led to diuresis, weight loss, and reduction of ascites. The physiologic process of the LeVeen shunt is reviewed and we suggest placement of a radiopaque marker into the tubing."} {"id": "PMID:1259569", "title": "Local recurrence of breast cancer.", "content": "Pathologic and surgical aspects of 1,027 breast cancer cases treated between 1961 and 1972 were reviewed. Sixty-eight (7%) of the cases recurred locally. This low rate of recurrence is associated with the small average diameter of 2.7 cm of all carcinomas and the correspondingly low rate of axillary lymph node metastasis of 40%. Subsequently recurring tumors had a higher incidence of axillary lymph node metastasis (68%). Eight hundred eighty-eight infiltrating duct carcinomas represented the largest group of cases and had a recurrence rate of 5.7%. Comedo, infiltrating papillary, and infiltrating lobular carcinomas recurred locally more frequently, but none of 26 mucinous carcinomas recurred. In eight cases, the recurrent tumor was of a more malignant histologic type than the primary lesion. The average width of the excised segments of skin decreased from 9.8 cm during the first three-year period (1961 to 1963) to 8.4 cm during the last period (1970 to 1972). The average width for the entire period was 9.1 cm, identical for locally recurring and nonrecurring tumors.", "contents": "Local recurrence of breast cancer. Pathologic and surgical aspects of 1,027 breast cancer cases treated between 1961 and 1972 were reviewed. Sixty-eight (7%) of the cases recurred locally. This low rate of recurrence is associated with the small average diameter of 2.7 cm of all carcinomas and the correspondingly low rate of axillary lymph node metastasis of 40%. Subsequently recurring tumors had a higher incidence of axillary lymph node metastasis (68%). Eight hundred eighty-eight infiltrating duct carcinomas represented the largest group of cases and had a recurrence rate of 5.7%. Comedo, infiltrating papillary, and infiltrating lobular carcinomas recurred locally more frequently, but none of 26 mucinous carcinomas recurred. In eight cases, the recurrent tumor was of a more malignant histologic type than the primary lesion. The average width of the excised segments of skin decreased from 9.8 cm during the first three-year period (1961 to 1963) to 8.4 cm during the last period (1970 to 1972). The average width for the entire period was 9.1 cm, identical for locally recurring and nonrecurring tumors."} {"id": "PMID:1259570", "title": "Implications of precancerous rectal biopsy in patients with inflammatory bowel disease.", "content": "Sixty-five patients with an initial diagnosis of ulcerative colitis who underwent total proctocolectomy between 1955 and 1973 were studied retrospectively. Rectal mucosa in each patient was examined microscopically for the presence or absence of \"precancerous\" alterations as described by Morson and Pang. Histologic examination was made with no knowledge of concomitant colon carcinoma or the patients' clinical courses. Three of ten patients with precancerous rectal mucosa had invasive colon carcinoma, while none of the 55 patients without such changes had colon cancer (P less than .05, Fischer exact test). The duration of disease was significantly greater in those patients with rectal precancer (P less than .05). Reexamination changed the pathologic diagnosis in 15 patients from ulcerative colitis to granulomatous or \"mixed\" colitis. Two of three invasive cancers occurred in the reclassified group. Results support previous contentions that careful histologic evaluation of rectal biopsy specimens from individuals with inflammatory bowel disease may better define that population of patients with an increased risk of colonic carcinoma.", "contents": "Implications of precancerous rectal biopsy in patients with inflammatory bowel disease. Sixty-five patients with an initial diagnosis of ulcerative colitis who underwent total proctocolectomy between 1955 and 1973 were studied retrospectively. Rectal mucosa in each patient was examined microscopically for the presence or absence of \"precancerous\" alterations as described by Morson and Pang. Histologic examination was made with no knowledge of concomitant colon carcinoma or the patients' clinical courses. Three of ten patients with precancerous rectal mucosa had invasive colon carcinoma, while none of the 55 patients without such changes had colon cancer (P less than .05, Fischer exact test). The duration of disease was significantly greater in those patients with rectal precancer (P less than .05). Reexamination changed the pathologic diagnosis in 15 patients from ulcerative colitis to granulomatous or \"mixed\" colitis. Two of three invasive cancers occurred in the reclassified group. Results support previous contentions that careful histologic evaluation of rectal biopsy specimens from individuals with inflammatory bowel disease may better define that population of patients with an increased risk of colonic carcinoma."} {"id": "PMID:1259571", "title": "Surgical treatment of hepatic metastases from colorectal cancers.", "content": "Follow-up data covering periods of two to 23 years have been collected on 60 patients who had resection of hepatic metastases for colorectal cancer. Multiple lesions were removed from 20 patients, and solitary lesions were excised from the other 40 patients. Only one patient died during hospital convalescence. No patient who had multiple lesions excised lived for five years. In contrast, 15 of the 36 patients eligible for five-year survival study who had resection of apparent solitary lesions lived for five years or more, and eight patients were alive without evidence of recurrence ten years or more after operation. These surprisingly favorable results of surgical treatment were analyzed in relation to results in patients who had biopsy specimens taken of lesions of comparable size and number, but no removal at the time of colonic resection. No patient in this control group lived for five years. Aggressive surgical treatment of apparent solitary hepatic metastatic lesions from colorectal cancer seems to be justified by the survival rate of surgically treated patients.", "contents": "Surgical treatment of hepatic metastases from colorectal cancers. Follow-up data covering periods of two to 23 years have been collected on 60 patients who had resection of hepatic metastases for colorectal cancer. Multiple lesions were removed from 20 patients, and solitary lesions were excised from the other 40 patients. Only one patient died during hospital convalescence. No patient who had multiple lesions excised lived for five years. In contrast, 15 of the 36 patients eligible for five-year survival study who had resection of apparent solitary lesions lived for five years or more, and eight patients were alive without evidence of recurrence ten years or more after operation. These surprisingly favorable results of surgical treatment were analyzed in relation to results in patients who had biopsy specimens taken of lesions of comparable size and number, but no removal at the time of colonic resection. No patient in this control group lived for five years. Aggressive surgical treatment of apparent solitary hepatic metastatic lesions from colorectal cancer seems to be justified by the survival rate of surgically treated patients."} {"id": "PMID:1259572", "title": "Aneurysms of extracranial carotid arteries.", "content": "Twenty-three extracranial carotid artery aneurysms were encountered in 19 patients. Arteriosclerosis was evident in 16 aneurysms. Severe arterial hypertension affected all patients with arteriosclerotic lesions. Trauma, penetrating neck injury once, and blunt neck injury three times caused four aneurysms. Three aneurysms resulted from earlier carotid artery operations. All 19 patients were symptomatic. Neurologic symptoms affected 13 individuals. Local symptoms referable to the aneurysmal mass troubled 15 patients. Twenty-one aneurysms were treated operatively. There was no operative mortality. Aneurysmectomy with arterial reconstruction was performed 16 times. Aneurysmorrhaphy was undertaken on four occasions and carotid ligation once. Two strokes and multiple cranial nerve injury accounted for three operative complications. No neurologic complications occurred during follow-up totaling 360 man-months. These lesions may be successfully treated by a carefully performed, properly selected operation.", "contents": "Aneurysms of extracranial carotid arteries. Twenty-three extracranial carotid artery aneurysms were encountered in 19 patients. Arteriosclerosis was evident in 16 aneurysms. Severe arterial hypertension affected all patients with arteriosclerotic lesions. Trauma, penetrating neck injury once, and blunt neck injury three times caused four aneurysms. Three aneurysms resulted from earlier carotid artery operations. All 19 patients were symptomatic. Neurologic symptoms affected 13 individuals. Local symptoms referable to the aneurysmal mass troubled 15 patients. Twenty-one aneurysms were treated operatively. There was no operative mortality. Aneurysmectomy with arterial reconstruction was performed 16 times. Aneurysmorrhaphy was undertaken on four occasions and carotid ligation once. Two strokes and multiple cranial nerve injury accounted for three operative complications. No neurologic complications occurred during follow-up totaling 360 man-months. These lesions may be successfully treated by a carefully performed, properly selected operation."} {"id": "PMID:1259573", "title": "Carotid body tumor: resection or reflection.", "content": "We have studied a series of 24 cases of carotid body tumor, comprising our total experience during the past two decades. Twelve patients had symptoms related to compression or invasion of the surrounding structures. Two patients had malignant changes, while three individuals had bilateral lesions. Thirteen patients underwent neck exploration for diagnosis or attempt at surgical removal of the tumor prior to admission to our institution. Definitive procedures in 24 cases resulted in one postoperative death, a rate of 4%. Internal carotid flow was preserved in every case. Intraluminal shunting was employed during the last decade, and no instance of cerebral damage was encountered. It is our intention to emphasize the importance of an accurate diagnosis by carotid angiography prior to surgical management. We also wish to encourage routine excision of these tumors as they are diagnosed, before they reach an enormous size.", "contents": "Carotid body tumor: resection or reflection. We have studied a series of 24 cases of carotid body tumor, comprising our total experience during the past two decades. Twelve patients had symptoms related to compression or invasion of the surrounding structures. Two patients had malignant changes, while three individuals had bilateral lesions. Thirteen patients underwent neck exploration for diagnosis or attempt at surgical removal of the tumor prior to admission to our institution. Definitive procedures in 24 cases resulted in one postoperative death, a rate of 4%. Internal carotid flow was preserved in every case. Intraluminal shunting was employed during the last decade, and no instance of cerebral damage was encountered. It is our intention to emphasize the importance of an accurate diagnosis by carotid angiography prior to surgical management. We also wish to encourage routine excision of these tumors as they are diagnosed, before they reach an enormous size."} {"id": "PMID:1259574", "title": "Transcervical thymectomy: an integral part of neck exploration for hyperparathyroidism.", "content": "Thirty-two neck explorations for hyperparathyroidism were done in 18 months. The indication for transcervical thymectomy was a failure to locate either inferior gland. Six of eight patients had adenomatous or hyperplastic glands located within or adjacent to the thymus. One infrathymic lesion was a parathyroid carcinoma and the other was a functioning parathyroid cyst. The abnormal parathyroid gland was not visible in any of these six patients until the thymus had been removed. Had this step been omitted, a sternotomy would probably have been required. Two patients had bilateral normal parathyroid glands within or deep to the thymus. Unless some normal parathyroid tissue has been identified and preserved, the indiscriminate use of transcervical thymectomy could result in the inadvertent excision of both inferior glands and possible iatrogenic hypoparathyroidism.", "contents": "Transcervical thymectomy: an integral part of neck exploration for hyperparathyroidism. Thirty-two neck explorations for hyperparathyroidism were done in 18 months. The indication for transcervical thymectomy was a failure to locate either inferior gland. Six of eight patients had adenomatous or hyperplastic glands located within or adjacent to the thymus. One infrathymic lesion was a parathyroid carcinoma and the other was a functioning parathyroid cyst. The abnormal parathyroid gland was not visible in any of these six patients until the thymus had been removed. Had this step been omitted, a sternotomy would probably have been required. Two patients had bilateral normal parathyroid glands within or deep to the thymus. Unless some normal parathyroid tissue has been identified and preserved, the indiscriminate use of transcervical thymectomy could result in the inadvertent excision of both inferior glands and possible iatrogenic hypoparathyroidism."} {"id": "PMID:1259575", "title": "Parietal cell vagotomy without drainage for treatment of duodenal ulcer. A two- to three-year follow-up report.", "content": "Parietal cell vagotomy (PCV) without drainage was performed on 35 patients. Three patients died during the study from causes unrelated to duodenal ulcer. Thirty-one (97%) of the remaining patients were followed up for two years; 66% have been studied after three years. At the end of two years, the mean basal acid output and peak hourly basal secretion rate were 43% and 47% less than the preoperative values, respectively. The number of patients with a negative insulin test result postoperatively fell from 64% of patients tested at two months to 44% at two years. The number of patients with an early positive insulin test result rose from 13% at two months to 28% at two years after operation. There were two recurrent duodenal ulcers; one required reoperation. A gastric ulcer developed in one patient who was taking massive doses of aspirin; the ulcer healed after aspirin withdrawal. One patient required operation for pyloric obstruction. Both dumping and diarrhea were reported by 7% of patients. These results suggest that PCV without drainage is an acceptable procedure for treatment of duodenal ulcer.", "contents": "Parietal cell vagotomy without drainage for treatment of duodenal ulcer. A two- to three-year follow-up report. Parietal cell vagotomy (PCV) without drainage was performed on 35 patients. Three patients died during the study from causes unrelated to duodenal ulcer. Thirty-one (97%) of the remaining patients were followed up for two years; 66% have been studied after three years. At the end of two years, the mean basal acid output and peak hourly basal secretion rate were 43% and 47% less than the preoperative values, respectively. The number of patients with a negative insulin test result postoperatively fell from 64% of patients tested at two months to 44% at two years. The number of patients with an early positive insulin test result rose from 13% at two months to 28% at two years after operation. There were two recurrent duodenal ulcers; one required reoperation. A gastric ulcer developed in one patient who was taking massive doses of aspirin; the ulcer healed after aspirin withdrawal. One patient required operation for pyloric obstruction. Both dumping and diarrhea were reported by 7% of patients. These results suggest that PCV without drainage is an acceptable procedure for treatment of duodenal ulcer."} {"id": "PMID:1259576", "title": "A plasma scalpel: comparison of tissue damage and wound healing with electrosurgical and steel scalpels.", "content": "We have been evaluating a plasma scalpel (the term has no relation to blood plasma) for four years that, with the generation of a small, hot gas jet (3,000 C), can cut tissue and simultaneously cauterize blood vessels of 3 mm in diameter. Twenty-nine plasma scalpel hepatectomies in dogs and comparative skin wound healing (with steel and electrosurgical scalpels) in 90 mice showed that bleeding was reduced, and the thermal insult in liver tissue was limited to 2 mm from the incision; both liver and mouse skin incisions healed without complication. The completion of epithelization of mouse skin wounds occurred at 2 to 6, 6 to 14, and 6 to 18 days, and the average scar width was 0.8, 1.4, and 2.1 mm for the steel, electrosurgical, and plasma scalpels, respectively. The plasma scalpel effectively cauterizes blood vessels as it cuts, leaving limited damaged tissue. We have recently begun human trials, and the device shows promise as a clinical tool.", "contents": "A plasma scalpel: comparison of tissue damage and wound healing with electrosurgical and steel scalpels. We have been evaluating a plasma scalpel (the term has no relation to blood plasma) for four years that, with the generation of a small, hot gas jet (3,000 C), can cut tissue and simultaneously cauterize blood vessels of 3 mm in diameter. Twenty-nine plasma scalpel hepatectomies in dogs and comparative skin wound healing (with steel and electrosurgical scalpels) in 90 mice showed that bleeding was reduced, and the thermal insult in liver tissue was limited to 2 mm from the incision; both liver and mouse skin incisions healed without complication. The completion of epithelization of mouse skin wounds occurred at 2 to 6, 6 to 14, and 6 to 18 days, and the average scar width was 0.8, 1.4, and 2.1 mm for the steel, electrosurgical, and plasma scalpels, respectively. The plasma scalpel effectively cauterizes blood vessels as it cuts, leaving limited damaged tissue. We have recently begun human trials, and the device shows promise as a clinical tool."} {"id": "PMID:1259577", "title": "The spectrum of pulmonary embolism: twenty years later.", "content": "A ten-year analysis of the prevalence of pulmonary embolism found at autopsy examination has been repeated 20 years after a prior study. The frequency of all pulmonary embolism (12.3%) and of \"major\" pulmonary emboli (7.1%) remains essentially unchanged from that detected 20 years previously (13.6% and 8.6%). Less than 10% of patients had the clinical diagnosis of deep leg vein thrombosis, and only 9.3% had a definitive diagnosis of pulmonary embolism made during life. A sixfold variation in quarterly frequency and a twofold variation in annual prevalence were noted. Since these wide fluctuations in frequency are present, any assumptions regarding a changing disease pattern must be made with great caution. There is no evidence that fatal pulmonary embolism has decreased in frequency in recent years. An effort should be made to increase rate of detection of thromboembolic disease by more widespread use of one or more of the recently developed diagnostic procedures, or a larger segment of the hospital population at risk should receive prophylactic therapy with \"low-dose\" heparin sodium.", "contents": "The spectrum of pulmonary embolism: twenty years later. A ten-year analysis of the prevalence of pulmonary embolism found at autopsy examination has been repeated 20 years after a prior study. The frequency of all pulmonary embolism (12.3%) and of \"major\" pulmonary emboli (7.1%) remains essentially unchanged from that detected 20 years previously (13.6% and 8.6%). Less than 10% of patients had the clinical diagnosis of deep leg vein thrombosis, and only 9.3% had a definitive diagnosis of pulmonary embolism made during life. A sixfold variation in quarterly frequency and a twofold variation in annual prevalence were noted. Since these wide fluctuations in frequency are present, any assumptions regarding a changing disease pattern must be made with great caution. There is no evidence that fatal pulmonary embolism has decreased in frequency in recent years. An effort should be made to increase rate of detection of thromboembolic disease by more widespread use of one or more of the recently developed diagnostic procedures, or a larger segment of the hospital population at risk should receive prophylactic therapy with \"low-dose\" heparin sodium."} {"id": "PMID:1259578", "title": "Kinetics of heparin administration.", "content": "Many clinicians prefer intravenous administration of heparin sodium because of unpredictable absorption from extravascular sites. In this experimental study, large doses of heparin labeled with sulfur 35 were injected into 34 dogs separated in groups according to dosage and route of administration. Anticoagulation and plasma heparin levels were assessed at half-hour intervals. Intravenous injection produced immediate anticoagulation followed by a predictable decline. Subcutaneous or intramuscular injection resulted in delayed onset and variable levels of anticoagulant activity. The wide range of response following intermittent injection suggests that continuous intravenous infusion offers a more reliable method of treatment.", "contents": "Kinetics of heparin administration. Many clinicians prefer intravenous administration of heparin sodium because of unpredictable absorption from extravascular sites. In this experimental study, large doses of heparin labeled with sulfur 35 were injected into 34 dogs separated in groups according to dosage and route of administration. Anticoagulation and plasma heparin levels were assessed at half-hour intervals. Intravenous injection produced immediate anticoagulation followed by a predictable decline. Subcutaneous or intramuscular injection resulted in delayed onset and variable levels of anticoagulant activity. The wide range of response following intermittent injection suggests that continuous intravenous infusion offers a more reliable method of treatment."} {"id": "PMID:1259579", "title": "A retrospective study of regional perfusion for melanoma.", "content": "Regional perfusion has been utilized in the treatment of accessible melanomas for many years. This series of 245 patients, which encompasses over ten years of experience, is presented to reevaluate the results of regional perfusions in melanomas, and perhaps to redefine the indications for such a procedure. Fifty-nine patients died from three months to over five years following the procedure, and six of the deaths were from diseases other than melanoma. The overall survival in stage I disease was 93%; stage II, 68%; and stage III, 41%. There were no survivors in stage IV. Nearly all of the recurrences and deaths from disease were seen within two years of the perfusion. These results are similar to others, and 10% to 15% better than those of conventional methods. Indications are now more definite, and include most invasive melanomas in an area accessible to perfusion technique, except in very elderly and poor risk patients, those with severe arteriosclerosis in the area concerned, and those with widespread metastases.", "contents": "A retrospective study of regional perfusion for melanoma. Regional perfusion has been utilized in the treatment of accessible melanomas for many years. This series of 245 patients, which encompasses over ten years of experience, is presented to reevaluate the results of regional perfusions in melanomas, and perhaps to redefine the indications for such a procedure. Fifty-nine patients died from three months to over five years following the procedure, and six of the deaths were from diseases other than melanoma. The overall survival in stage I disease was 93%; stage II, 68%; and stage III, 41%. There were no survivors in stage IV. Nearly all of the recurrences and deaths from disease were seen within two years of the perfusion. These results are similar to others, and 10% to 15% better than those of conventional methods. Indications are now more definite, and include most invasive melanomas in an area accessible to perfusion technique, except in very elderly and poor risk patients, those with severe arteriosclerosis in the area concerned, and those with widespread metastases."} {"id": "PMID:1259580", "title": "Congenital arteriovenous anomalies of the limbs.", "content": "Observations in 33 patients with congenital arteriovenous fistulas described ten years ago have been extended with the addition of 49 other cases; the clinical, pathologic, and roentgenographic characteristics of these lesions in the entire group of 82 patients have been summarized. The findings in the entire group over the additional observation period have confirmed the conclusions previously reached, namely, that (1) these clinically extremely varied lesions have a unitary (developmental) cause; (2) for rational management, angiographic investigation is indispensable to establish their extent and complexity; (3) with few exceptions, their radical cure by surgical means is impossible; and (4) the large majority of patients do well on a carefully supervised conservative regimen, with surgical intervention reserved for individually defined instances.", "contents": "Congenital arteriovenous anomalies of the limbs. Observations in 33 patients with congenital arteriovenous fistulas described ten years ago have been extended with the addition of 49 other cases; the clinical, pathologic, and roentgenographic characteristics of these lesions in the entire group of 82 patients have been summarized. The findings in the entire group over the additional observation period have confirmed the conclusions previously reached, namely, that (1) these clinically extremely varied lesions have a unitary (developmental) cause; (2) for rational management, angiographic investigation is indispensable to establish their extent and complexity; (3) with few exceptions, their radical cure by surgical means is impossible; and (4) the large majority of patients do well on a carefully supervised conservative regimen, with surgical intervention reserved for individually defined instances."} {"id": "PMID:1259581", "title": "Pancreatic ascites: recognition and management.", "content": "In a patient with chronic ascites, an abnormally raised ascitic fluid amylase concentration and a protein content above 2.5 gm/100 ml is diagnostic of pancreatic ascites. Thirty-one episodes in 26 patients treated between 1958 and 1975 have been analyzed. Twenty patients (65%) experienced abdominal pain and ten (32%) had concomitant pleural effusions roentgenographically. Although a leaking pancreatic pseudocyst was the cause of ascites in at least 21 episodes (70%), an abdominal mass could only be palpated in two of 26 patients. Roentgenographic series of the upper part of the gastrointestinal tract failed to demonstrate pancreatic pseudocyst in 7 of 21 episodes (33%). Endoscopic retrograde pancreatography is invaluable in delineating the pancreatic ductal system and, in conjunction with intraoperative pancreatography, makes a vital contribution to rational surgical therapy. Medical treatment or external drainage during 18 episodes resulted in death in four (22%) and recurrences of ascites or pancreatic pseudocyst in nine (64%). Since routine pancreatography followed by pancreatic resection or internal drainage has been instituted, mortality and recurrence have been reduced to zero.", "contents": "Pancreatic ascites: recognition and management. In a patient with chronic ascites, an abnormally raised ascitic fluid amylase concentration and a protein content above 2.5 gm/100 ml is diagnostic of pancreatic ascites. Thirty-one episodes in 26 patients treated between 1958 and 1975 have been analyzed. Twenty patients (65%) experienced abdominal pain and ten (32%) had concomitant pleural effusions roentgenographically. Although a leaking pancreatic pseudocyst was the cause of ascites in at least 21 episodes (70%), an abdominal mass could only be palpated in two of 26 patients. Roentgenographic series of the upper part of the gastrointestinal tract failed to demonstrate pancreatic pseudocyst in 7 of 21 episodes (33%). Endoscopic retrograde pancreatography is invaluable in delineating the pancreatic ductal system and, in conjunction with intraoperative pancreatography, makes a vital contribution to rational surgical therapy. Medical treatment or external drainage during 18 episodes resulted in death in four (22%) and recurrences of ascites or pancreatic pseudocyst in nine (64%). Since routine pancreatography followed by pancreatic resection or internal drainage has been instituted, mortality and recurrence have been reduced to zero."} {"id": "PMID:1259582", "title": "Nonoperative extraction of retained common duct stones.", "content": "Nonoperative extraction of retained common duct stones was successful in 17 patients during the past two years. Eleven required only one manipulation; the largest number of manipulations required was five. The Burhenne catheter and Dormia basket were employed frequently, but were not always effective. When difficulties occurred with their use, Mazzariello biliary forceps resulted in successful stone extraction, particularly in the management of impacted stones. Extraction procedures were performed under fluoroscopic control, usually on an outpatient basis. Recently, we have employed a flexible fiberoptic endoscope that allows visual investigation of suspected defects and decreases fluoroscopic exposure. These results indicate that all patients with retained common duct stones are candidates for sinus tract manipulation six weeks after common duct exploration. It is recommended that secondary operations for retained common duct calculi not be performed until nonoperative extraction has been given an appropriate trial.", "contents": "Nonoperative extraction of retained common duct stones. Nonoperative extraction of retained common duct stones was successful in 17 patients during the past two years. Eleven required only one manipulation; the largest number of manipulations required was five. The Burhenne catheter and Dormia basket were employed frequently, but were not always effective. When difficulties occurred with their use, Mazzariello biliary forceps resulted in successful stone extraction, particularly in the management of impacted stones. Extraction procedures were performed under fluoroscopic control, usually on an outpatient basis. Recently, we have employed a flexible fiberoptic endoscope that allows visual investigation of suspected defects and decreases fluoroscopic exposure. These results indicate that all patients with retained common duct stones are candidates for sinus tract manipulation six weeks after common duct exploration. It is recommended that secondary operations for retained common duct calculi not be performed until nonoperative extraction has been given an appropriate trial."} {"id": "PMID:1259583", "title": "Custom implants for reconstruction of craniofacial defects.", "content": "This method deals with the fabrication of a custom silicone implant using Dow Corning Medical Grade Elastomer 382 (room-temperature vulcanizing silicone). The technique has been utilized in 34 cases during the past five years with a satisfactory end result in 33 of the 34 cases. This method, which appears to be quite accurate in obliterating the obvious defect, is simple in its execution and reduces the overall amount of operative time, since no carving or manipulation is necessary. It avoids unsightly \"donor scars,\" and in some instances, the surgery can be done on an outpatient basis.", "contents": "Custom implants for reconstruction of craniofacial defects. This method deals with the fabrication of a custom silicone implant using Dow Corning Medical Grade Elastomer 382 (room-temperature vulcanizing silicone). The technique has been utilized in 34 cases during the past five years with a satisfactory end result in 33 of the 34 cases. This method, which appears to be quite accurate in obliterating the obvious defect, is simple in its execution and reduces the overall amount of operative time, since no carving or manipulation is necessary. It avoids unsightly \"donor scars,\" and in some instances, the surgery can be done on an outpatient basis."} {"id": "PMID:1259584", "title": "Anterior approach to the thoracolumbar spine: technical considerations.", "content": "Forty-five patients, of whom most were children, underwent extensive exposure of the thoracolumbar spine to correct serious orthopedic abnormalities. The spine was exposed through a combined thoracotomy and retroperitoneal approach that gave excellent access with minimal morbidity. The diaphragm was opened circumferentially after the peritoneum had been dissected from its muscular portion. This permitted repair of the diaphragm with no detectable loss of function. Although this approach was developed for exposure of the spine, it can also be utilized to expose the entire aorta, both kidneys and their blood supply, and the retroperitoneal area for possible excision of large tumors.", "contents": "Anterior approach to the thoracolumbar spine: technical considerations. Forty-five patients, of whom most were children, underwent extensive exposure of the thoracolumbar spine to correct serious orthopedic abnormalities. The spine was exposed through a combined thoracotomy and retroperitoneal approach that gave excellent access with minimal morbidity. The diaphragm was opened circumferentially after the peritoneum had been dissected from its muscular portion. This permitted repair of the diaphragm with no detectable loss of function. Although this approach was developed for exposure of the spine, it can also be utilized to expose the entire aorta, both kidneys and their blood supply, and the retroperitoneal area for possible excision of large tumors."} {"id": "PMID:1259585", "title": "A neuromuscular basis for development of indirect inguinal hernia.", "content": "Specialized portions of the transversus abdominus muscles act on the internal inguinal rings and produce a closure mechanism during voluntary abdominal muscular activity. Abdominal muscular contractions may have a protective influence against development of indirect inguinal hernia. It follows, therefore, that injury or inactivation of this mechanism may be an etiologic factor in the development of indirect inguinal hernia. One cause of injury to this mechanism is by denervation and regional muscle paralysis occurring during a surgical procedure. Surgical denervation appears to have caused an indirect inguinal hernia in one of the authors.", "contents": "A neuromuscular basis for development of indirect inguinal hernia. Specialized portions of the transversus abdominus muscles act on the internal inguinal rings and produce a closure mechanism during voluntary abdominal muscular activity. Abdominal muscular contractions may have a protective influence against development of indirect inguinal hernia. It follows, therefore, that injury or inactivation of this mechanism may be an etiologic factor in the development of indirect inguinal hernia. One cause of injury to this mechanism is by denervation and regional muscle paralysis occurring during a surgical procedure. Surgical denervation appears to have caused an indirect inguinal hernia in one of the authors."} {"id": "PMID:1259586", "title": "The treatment of incidental thyroid cancer.", "content": "Thirty-eight patients with incidental thyroid carcinoma were reviewed. Thyroid lobectomy was adequate therapy in 15 to 17 patients. Both patients in whom lobectomy alone was inadequate had received prior irradiation. Five patients had antecedent head and neck irradiation, and in three of them, multicentric foci of tumor developed. Lobectomy alone was inadequate in three of these patients; they required thyroidectomy. A clinical recurrence developed in only two of 38 patients, and both of them had received previous irradiation. Reoperation in previously dissected areas was associated with an increased rate of complications. Lobectomy in nonirradiated and total thyroidectomy in irradiated patients cured the majority of patients suffering from incidental carcinoma of the thyroid.", "contents": "The treatment of incidental thyroid cancer. Thirty-eight patients with incidental thyroid carcinoma were reviewed. Thyroid lobectomy was adequate therapy in 15 to 17 patients. Both patients in whom lobectomy alone was inadequate had received prior irradiation. Five patients had antecedent head and neck irradiation, and in three of them, multicentric foci of tumor developed. Lobectomy alone was inadequate in three of these patients; they required thyroidectomy. A clinical recurrence developed in only two of 38 patients, and both of them had received previous irradiation. Reoperation in previously dissected areas was associated with an increased rate of complications. Lobectomy in nonirradiated and total thyroidectomy in irradiated patients cured the majority of patients suffering from incidental carcinoma of the thyroid."} {"id": "PMID:1259587", "title": "Blunt abdominal trauma: a prospective study with selective peritoneal lavage.", "content": "To determine the effectiveness of clinical evaluation and peritoneal lavage in blunt abdominal trauma, a prospective study was undertaken in 315 consecutive patients suspected of having this injury. Conscious patients with obvious physical findings were operated on without peritoneal lavage, and a diagnostic accuracy of 96% was achieved. In patients with altered states of consciousness, peritoneal lavage was studied prospectively for equivocal physical findings. An overall accuracy of 97% was achieved in such patients by peritoneal lavage. Peritoneal lavage was helpful in reducing the rate of normal findings at laparotomy by 50% in patients with altered states of consciousness and equivocal physical findings. Patients with normal findings on peritoneal lavage and subsequent deterioration had normal findings at laparotomy, which points to the value of further evaluation in such patients before laparotomy is carried out. Mortality is ultimately determined by the severity of the injury, despite early and definitive diagnosis and aggressive management.", "contents": "Blunt abdominal trauma: a prospective study with selective peritoneal lavage. To determine the effectiveness of clinical evaluation and peritoneal lavage in blunt abdominal trauma, a prospective study was undertaken in 315 consecutive patients suspected of having this injury. Conscious patients with obvious physical findings were operated on without peritoneal lavage, and a diagnostic accuracy of 96% was achieved. In patients with altered states of consciousness, peritoneal lavage was studied prospectively for equivocal physical findings. An overall accuracy of 97% was achieved in such patients by peritoneal lavage. Peritoneal lavage was helpful in reducing the rate of normal findings at laparotomy by 50% in patients with altered states of consciousness and equivocal physical findings. Patients with normal findings on peritoneal lavage and subsequent deterioration had normal findings at laparotomy, which points to the value of further evaluation in such patients before laparotomy is carried out. Mortality is ultimately determined by the severity of the injury, despite early and definitive diagnosis and aggressive management."} {"id": "PMID:1259588", "title": "Management of 1,590 consecutive cases of liver trauma.", "content": "Between 1939 and 1974, more than 1,500 patients have been treated for penetrating or blunt liver trauma at our institution. Gunshot wounds and major blunt trauma have increased, stab wounds decreased, as percent of total. In most cases techniques other than partial hepatic resection were used, although this was performed in 49 instances. Choledochostomy was infrequently employed. Intracaval shunts were useful in 15 selected patients with massive hepatic, concomitant suprarenal vena caval, or hepatic vein injuries. The overall mortality of this group was 13.1%. The improvement in mortality from liver injuries is attributable to (1) early exploration for suspected intra-abdominal traumatic injury, (2) a conservative approach to the liver injury, and (3) the limitation of lobar resection, vascular cannulae, and afferent vascular compression to highly selected cases.", "contents": "Management of 1,590 consecutive cases of liver trauma. Between 1939 and 1974, more than 1,500 patients have been treated for penetrating or blunt liver trauma at our institution. Gunshot wounds and major blunt trauma have increased, stab wounds decreased, as percent of total. In most cases techniques other than partial hepatic resection were used, although this was performed in 49 instances. Choledochostomy was infrequently employed. Intracaval shunts were useful in 15 selected patients with massive hepatic, concomitant suprarenal vena caval, or hepatic vein injuries. The overall mortality of this group was 13.1%. The improvement in mortality from liver injuries is attributable to (1) early exploration for suspected intra-abdominal traumatic injury, (2) a conservative approach to the liver injury, and (3) the limitation of lobar resection, vascular cannulae, and afferent vascular compression to highly selected cases."} {"id": "PMID:1259592", "title": "The structural polypeptides of sowthistle yellow vein virus (SYVV).", "content": "The four structural polypeptides of SYYV have molecular weights of 71,000, 60,000, 42,000 and 36,000 daltons. The virus was shown colorimetrically to contain RNA.", "contents": "The structural polypeptides of sowthistle yellow vein virus (SYVV). The four structural polypeptides of SYYV have molecular weights of 71,000, 60,000, 42,000 and 36,000 daltons. The virus was shown colorimetrically to contain RNA."} {"id": "PMID:1259593", "title": "Isolation and characterization of double stranded RNA containing infectious viral genome RNA from cells infected with Semliki Forest virus.", "content": "A double stranded virus specific RNA sedimenting at about 19S on sucrose density gradients has been isolated from BHK-21 cells infected with Semliki Forest virus (SFV). The molecule consists of double stranded RNA (ds RNA) since it is labeled with 3H-uridine, is soluble in 2 M LiCl, resistant against treatment with DNase and RNase at 2 X SSC, hydrolyzed by alkali treatment, has a sharp thermal melting point at 89 degrees in 1/10SSC, and an extended appearance under non denaturing conditions in the electronmicroscope. The following findings show that it consists of intact, infectious 42S RNA similar or identical to the genome RNA of SFV complexed to a complementary 42S minus strand RNA: 1. Denaturation converts the ds RNA into molecules cosedimenting with 42S RNA isolated from SFV particles. 2. About 50% of the radioactivity of 3H-uridine labeled 42S RNA molecules generated from 19S ds RNA by denaturation hybridizes to 42S viral RNA. 3. The specific infectivity of denatured 19S ds RNA is about half of that of similarly treated viral 42S RNA. Further properties of this molecule are discussed.", "contents": "Isolation and characterization of double stranded RNA containing infectious viral genome RNA from cells infected with Semliki Forest virus. A double stranded virus specific RNA sedimenting at about 19S on sucrose density gradients has been isolated from BHK-21 cells infected with Semliki Forest virus (SFV). The molecule consists of double stranded RNA (ds RNA) since it is labeled with 3H-uridine, is soluble in 2 M LiCl, resistant against treatment with DNase and RNase at 2 X SSC, hydrolyzed by alkali treatment, has a sharp thermal melting point at 89 degrees in 1/10SSC, and an extended appearance under non denaturing conditions in the electronmicroscope. The following findings show that it consists of intact, infectious 42S RNA similar or identical to the genome RNA of SFV complexed to a complementary 42S minus strand RNA: 1. Denaturation converts the ds RNA into molecules cosedimenting with 42S RNA isolated from SFV particles. 2. About 50% of the radioactivity of 3H-uridine labeled 42S RNA molecules generated from 19S ds RNA by denaturation hybridizes to 42S viral RNA. 3. The specific infectivity of denatured 19S ds RNA is about half of that of similarly treated viral 42S RNA. Further properties of this molecule are discussed."} {"id": "PMID:1259594", "title": "Kinetics of reactions of antihemagglutinin and antineuraminidase antibodies with H2N2 and H3N2 influenza virus strains and description of a modification of the photometric ACU method for titration of antineuraminidase antibodies.", "content": "The isotherms describing the reactions of selected H2N2 and H3N2 virus strains with antihemagglutinin (AH) and antineuraminidase (AN) antibodies were established by use of a photometric hemagglutination inhibition test [antibody concentration unit (ACU) method]. It was found that the AN antibody isotherms had significantly higher values of the constant 1/N than did the AH antibody isotherms. This finding confirms for further virus strains the conclusion that the photometric ACU method can discriminate objectively between AN and AH antibodies. The results obtained when determining by use of the photometric ACU method the kinetics of reactions of AN antibodies oriented to A/Bel (HO)-A/Sing (N2) virus with the neuraminidases of H2N2 and H3N2 strains, and vice versa, indicated that the N2 neuraminidases of the test strains could be divided into the following groups: One group comprising the strains A/Sing/1/57 and A/AA/1/65, a second comprising the strains A/Hong Kong/1/68 and A/England/42/72 and a third represented by A/Port Chalmers/1/73. This finding indicated progressive antigenic variation of the neuraminidases of the strains tested. A modification of the photometric ACU method for the titration of AN antibodies oriented to N2 strains has been developed. The modified technique was found to be more sensitive and accurate than was AN antibody titration by means of enzyme inhibition and HI pattern test.", "contents": "Kinetics of reactions of antihemagglutinin and antineuraminidase antibodies with H2N2 and H3N2 influenza virus strains and description of a modification of the photometric ACU method for titration of antineuraminidase antibodies. The isotherms describing the reactions of selected H2N2 and H3N2 virus strains with antihemagglutinin (AH) and antineuraminidase (AN) antibodies were established by use of a photometric hemagglutination inhibition test [antibody concentration unit (ACU) method]. It was found that the AN antibody isotherms had significantly higher values of the constant 1/N than did the AH antibody isotherms. This finding confirms for further virus strains the conclusion that the photometric ACU method can discriminate objectively between AN and AH antibodies. The results obtained when determining by use of the photometric ACU method the kinetics of reactions of AN antibodies oriented to A/Bel (HO)-A/Sing (N2) virus with the neuraminidases of H2N2 and H3N2 strains, and vice versa, indicated that the N2 neuraminidases of the test strains could be divided into the following groups: One group comprising the strains A/Sing/1/57 and A/AA/1/65, a second comprising the strains A/Hong Kong/1/68 and A/England/42/72 and a third represented by A/Port Chalmers/1/73. This finding indicated progressive antigenic variation of the neuraminidases of the strains tested. A modification of the photometric ACU method for the titration of AN antibodies oriented to N2 strains has been developed. The modified technique was found to be more sensitive and accurate than was AN antibody titration by means of enzyme inhibition and HI pattern test."} {"id": "PMID:1259595", "title": "Genetic exclusion and stable complementation of Sindbis virus.", "content": "In an effort to enhance genetic interactions by eliminating spatial or physical barriers between variants of Sindbis virus MgCl2 was used to aggregate infecting viral particles. Mixing viral samples in a 1:1 ratio with 0.5 M MgCl2 produced maximal reduction in plaque forming units (PFU) with minimal cell damage due to MgCl2. Aggregate size was determined to be about 7 PFU. Samples taken at 3,5 and 10 hours after infection with mixed aggregates composed of large and small plaque forming virus indicated that only one type of genome was represented among the progeny particles. In addition, aggregation enhanced complementation and the progeny were stable after several cycles of sonication and passage.", "contents": "Genetic exclusion and stable complementation of Sindbis virus. In an effort to enhance genetic interactions by eliminating spatial or physical barriers between variants of Sindbis virus MgCl2 was used to aggregate infecting viral particles. Mixing viral samples in a 1:1 ratio with 0.5 M MgCl2 produced maximal reduction in plaque forming units (PFU) with minimal cell damage due to MgCl2. Aggregate size was determined to be about 7 PFU. Samples taken at 3,5 and 10 hours after infection with mixed aggregates composed of large and small plaque forming virus indicated that only one type of genome was represented among the progeny particles. In addition, aggregation enhanced complementation and the progeny were stable after several cycles of sonication and passage."} {"id": "PMID:1259596", "title": "Efficacy and immune response to rubella subunits vaccines.", "content": "Antibody and cell-mediated immunity (CMI) was measured in rabbits immunized with wild or attenuated virus and in rabbits vaccinated with a rubella subunit vaccine containing the viral envelope or nucleocapsid. The data presented show that a subunit vaccine containing the envelope proteins could induce a good antibody and CMI response. The results also suggest that such a vaccine was highly effective since 60 per cent of the rabbits immunized with the envelope proteins were protected when challenged with wild virus. This protection rate was identical as the protection achieved with a live attenuated vaccine.", "contents": "Efficacy and immune response to rubella subunits vaccines. Antibody and cell-mediated immunity (CMI) was measured in rabbits immunized with wild or attenuated virus and in rabbits vaccinated with a rubella subunit vaccine containing the viral envelope or nucleocapsid. The data presented show that a subunit vaccine containing the envelope proteins could induce a good antibody and CMI response. The results also suggest that such a vaccine was highly effective since 60 per cent of the rabbits immunized with the envelope proteins were protected when challenged with wild virus. This protection rate was identical as the protection achieved with a live attenuated vaccine."} {"id": "PMID:1259598", "title": "[Maturation and fertilization of human ova outside of the body].", "content": "The egg-cells were obtained from ovaries removed for different clinical reasons and cultivated after Edward's technique with modifications to complete the maturation division. The process of fecundation, formation of pronucleuses, separation of the 2nd pole body and the first stage of egg-cell cleavage (up to the stage of 3 blastomeres). Non-fertilized egg-cells underwent random fragmentation into blastomere-like nucleus-free particles.", "contents": "[Maturation and fertilization of human ova outside of the body]. The egg-cells were obtained from ovaries removed for different clinical reasons and cultivated after Edward's technique with modifications to complete the maturation division. The process of fecundation, formation of pronucleuses, separation of the 2nd pole body and the first stage of egg-cell cleavage (up to the stage of 3 blastomeres). Non-fertilized egg-cells underwent random fragmentation into blastomere-like nucleus-free particles."} {"id": "PMID:1259599", "title": "[Morphofunctional characteristics of the lipids in the early embryogeny of placental mammals].", "content": "The comparative cytological study of lipids points to species specific character of lipid metabolism in early embryogenesis of placentate mammals. The general level of lipid metabolism is genetically determined in oogenesis being expressed by different loading of the ooplasm with substances of lipoid nature. At the cleavage stage lipids play a plastic role. Their significance as functionally active complexes is manifested in the period of the blastocyst formation, which is dependent on morphological differentiation and the beginning of the trophoblast functioning as an early metabolic organ.", "contents": "[Morphofunctional characteristics of the lipids in the early embryogeny of placental mammals]. The comparative cytological study of lipids points to species specific character of lipid metabolism in early embryogenesis of placentate mammals. The general level of lipid metabolism is genetically determined in oogenesis being expressed by different loading of the ooplasm with substances of lipoid nature. At the cleavage stage lipids play a plastic role. Their significance as functionally active complexes is manifested in the period of the blastocyst formation, which is dependent on morphological differentiation and the beginning of the trophoblast functioning as an early metabolic organ."} {"id": "PMID:1259600", "title": "[Trace element content in the internal female genitalia of the fetus in the 2d half of pregnancy].", "content": "The dynamics of increasing the concentration of microelements in the ovary, uterine tubes, uterus and vagina in the second half of intrauterine life were studied. Changes in the concentration of microelements depend on increasing the weight of the organs in question beginning from the 4th up to the 10th month of the fetal period. Hence, copper, zinc, manganese, titanium, lead, molybdenum are necessary for development and formation of internal female genitalia.", "contents": "[Trace element content in the internal female genitalia of the fetus in the 2d half of pregnancy]. The dynamics of increasing the concentration of microelements in the ovary, uterine tubes, uterus and vagina in the second half of intrauterine life were studied. Changes in the concentration of microelements depend on increasing the weight of the organs in question beginning from the 4th up to the 10th month of the fetal period. Hence, copper, zinc, manganese, titanium, lead, molybdenum are necessary for development and formation of internal female genitalia."} {"id": "PMID:1259601", "title": "[Collagen synthesis by osteoblasts in the maxilla in rats during the embryonic period].", "content": "Under study was the intensity of the collagen synthesis by osteoblasts of the primordium of the rat's maxilla at different terms of embryogenesis. Autoradiographic method revealed that the greatest part of incorporated glycin was used for construction of collagenous molecules, and the least part--for the synthesis of other cytoplasmic proteins of osteoblast. Different intensity of the synthesis of de novo collagen was established at different stages of embryogenesis. The most intensive synthesis of collagen was found to begin from the 18th day of the maxillary bone primordium development.", "contents": "[Collagen synthesis by osteoblasts in the maxilla in rats during the embryonic period]. Under study was the intensity of the collagen synthesis by osteoblasts of the primordium of the rat's maxilla at different terms of embryogenesis. Autoradiographic method revealed that the greatest part of incorporated glycin was used for construction of collagenous molecules, and the least part--for the synthesis of other cytoplasmic proteins of osteoblast. Different intensity of the synthesis of de novo collagen was established at different stages of embryogenesis. The most intensive synthesis of collagen was found to begin from the 18th day of the maxillary bone primordium development."} {"id": "PMID:1259602", "title": "[Development of the neural and tissue components of the excretory ducts of the liver, pancreas and Odd's sphincter in human embryogeny].", "content": "The development of pancreatic, hepatic, cystic, common bile ducts, the Oddi's sphincter and their nervous apparatus were studied during prenatal human ontogenesis of fetuses and newborns. The process of formation of the nervous apparatus corresponds to the development of tissue structures of the ducts and the sphincter. The distinctions in the organization of nervous elements which are noted in adult humans are laid in the process of embryogenesis. These distinctions are especially pronounced in the structure of nervous plexuses and receptory endings. The nervous apparatus of the Oddi's sphincter region has a complex arrangement. This is the site of concentration of nerve nodules and receptory endings as well as abundant nervous connections between plexuses of the pancreatic head, duodenum and orifice zones of the both ducts. The receptors in nerve nodules and pericellular apparatuses on the bodies of ganglionic neurons were revealed.", "contents": "[Development of the neural and tissue components of the excretory ducts of the liver, pancreas and Odd's sphincter in human embryogeny]. The development of pancreatic, hepatic, cystic, common bile ducts, the Oddi's sphincter and their nervous apparatus were studied during prenatal human ontogenesis of fetuses and newborns. The process of formation of the nervous apparatus corresponds to the development of tissue structures of the ducts and the sphincter. The distinctions in the organization of nervous elements which are noted in adult humans are laid in the process of embryogenesis. These distinctions are especially pronounced in the structure of nervous plexuses and receptory endings. The nervous apparatus of the Oddi's sphincter region has a complex arrangement. This is the site of concentration of nerve nodules and receptory endings as well as abundant nervous connections between plexuses of the pancreatic head, duodenum and orifice zones of the both ducts. The receptors in nerve nodules and pericellular apparatuses on the bodies of ganglionic neurons were revealed."} {"id": "PMID:1259603", "title": "[Reaction of the peripheral nervous system elements to the action of laser irradiation].", "content": "The effect of light of the helium neon laser LG-75 with the output power 25mvt and the generated wave length 6328 A upon reparative processes in the neuromuscular apparatus was studied in rats in dynamics after neurotomy of the ischiatic nerve. Neurohistological (staining after Bielschowski-Gross, Spielmeier, Weigert-Pal) and electrophysiological (chronaximetry, \"force-duration\" index, electromyography) methods were used. The material was processed in a computer. A stimulating effect of the applied low-energy laser radiation on the regeneration of the ischiatic nerve was established.", "contents": "[Reaction of the peripheral nervous system elements to the action of laser irradiation]. The effect of light of the helium neon laser LG-75 with the output power 25mvt and the generated wave length 6328 A upon reparative processes in the neuromuscular apparatus was studied in rats in dynamics after neurotomy of the ischiatic nerve. Neurohistological (staining after Bielschowski-Gross, Spielmeier, Weigert-Pal) and electrophysiological (chronaximetry, \"force-duration\" index, electromyography) methods were used. The material was processed in a computer. A stimulating effect of the applied low-energy laser radiation on the regeneration of the ischiatic nerve was established."} {"id": "PMID:1259604", "title": "[Morphological analysis of the adaptive changes in the myocardium under individually measured physical load].", "content": "Studying morphological changes of the myocardium in the organic, cellular and subcellular levels of experimental animals (dogs) has shown that standard physical load on tradmill band graded only by external parameters of work (time of running, its speed etc.) causes different changes in different animals. In contrast to it, the method of individually graded physical load proposed by the author (1970, 1972) considers the depth of myocardium responses, the degree of its morphofunctional changes corresponding to certain stages of changes in the parameters of cardio-vascular activity and respiratory system. Using the relationship of pulse rate and frequency of respiration as a diagnostic test made it possible to establish 6 stages of myocardium responses to physical load. Each of these stages has a complex of morpho-functional changes in the myocardium and corresponds to certain adaptive shifts on the organism level. On these foundations one can prognoze the depth of morphological changes in the myocardium basing upon diagnostic tests. So, the proposed experimental model of individual selection of the value of physical load according to responses of the organism rather than to external parameters of work as well as the established principle of the stage character of adaptive responses may be used in the practice of investigators for directed influence on the myocardium to form its certain qualities.", "contents": "[Morphological analysis of the adaptive changes in the myocardium under individually measured physical load]. Studying morphological changes of the myocardium in the organic, cellular and subcellular levels of experimental animals (dogs) has shown that standard physical load on tradmill band graded only by external parameters of work (time of running, its speed etc.) causes different changes in different animals. In contrast to it, the method of individually graded physical load proposed by the author (1970, 1972) considers the depth of myocardium responses, the degree of its morphofunctional changes corresponding to certain stages of changes in the parameters of cardio-vascular activity and respiratory system. Using the relationship of pulse rate and frequency of respiration as a diagnostic test made it possible to establish 6 stages of myocardium responses to physical load. Each of these stages has a complex of morpho-functional changes in the myocardium and corresponds to certain adaptive shifts on the organism level. On these foundations one can prognoze the depth of morphological changes in the myocardium basing upon diagnostic tests. So, the proposed experimental model of individual selection of the value of physical load according to responses of the organism rather than to external parameters of work as well as the established principle of the stage character of adaptive responses may be used in the practice of investigators for directed influence on the myocardium to form its certain qualities."} {"id": "PMID:1259605", "title": "[Morphological changes in the anterior lobe of the hypophysis in allotransplantation].", "content": "Under study were histological changes resulting from rejection of adenohypophysis allotransplantat without special influence upon the recipient immunity. The allotransplantat rejection was established to be accompanied by pronounced morphological changes in the adenohypophysis. Delta-basophils were the first to loose their granules, and beta-basophils showed more moderate degranulation. Acidophils were preserved for a longer period. The chromophobes were more resistant cellular elements. Simultaneously the cells were dying at all stages of their conversion. The fibrous connective tissue alone was observed at the site of allotransplantat 32-35 days after transplantation.", "contents": "[Morphological changes in the anterior lobe of the hypophysis in allotransplantation]. Under study were histological changes resulting from rejection of adenohypophysis allotransplantat without special influence upon the recipient immunity. The allotransplantat rejection was established to be accompanied by pronounced morphological changes in the adenohypophysis. Delta-basophils were the first to loose their granules, and beta-basophils showed more moderate degranulation. Acidophils were preserved for a longer period. The chromophobes were more resistant cellular elements. Simultaneously the cells were dying at all stages of their conversion. The fibrous connective tissue alone was observed at the site of allotransplantat 32-35 days after transplantation."} {"id": "PMID:1259606", "title": "[Kinetics of chondrocyte proliferation in cartilaginous anlagen and in forming skeletal metaepiphyseal cartilage of mammalian extremities].", "content": "Changes of proliferative properties of the cartilage cells were observed from the beginning of the formation of chondroblastema till the formation of the joint and metaepiphysial cartilages by the method of autoradiography with H3-thymidin. The greatest amount of dividing chondrocytes is localized in intermediate zones. In the metaepiphysial cartilage such cells form the proliferation zone and the duration of the mitotic cycle does not substantially differ from that of differentiating embryonic cells. The cells of the reserve zone of the metaepiphysial cartilage which are being formed are shown to be quite differentiated and to be at rest (phase G0). They can recommence division and stimulate general metabolic activity, replenishing the pool of proliferating chondrocytes. The duration of separate periods of the mitotic cycle for differentiating cells of different parts of the cartilage is calculated.", "contents": "[Kinetics of chondrocyte proliferation in cartilaginous anlagen and in forming skeletal metaepiphyseal cartilage of mammalian extremities]. Changes of proliferative properties of the cartilage cells were observed from the beginning of the formation of chondroblastema till the formation of the joint and metaepiphysial cartilages by the method of autoradiography with H3-thymidin. The greatest amount of dividing chondrocytes is localized in intermediate zones. In the metaepiphysial cartilage such cells form the proliferation zone and the duration of the mitotic cycle does not substantially differ from that of differentiating embryonic cells. The cells of the reserve zone of the metaepiphysial cartilage which are being formed are shown to be quite differentiated and to be at rest (phase G0). They can recommence division and stimulate general metabolic activity, replenishing the pool of proliferating chondrocytes. The duration of separate periods of the mitotic cycle for differentiating cells of different parts of the cartilage is calculated."} {"id": "PMID:1259607", "title": "[Changes in the thyrocytes to the administration of intermedin under conditions of the aminazine-altered functional state of the nervous system].", "content": "Histological and electron microscopial investigations of the thyroid gland were performed in white mice after exogeneous administration of intermedin (MSH) and intermedin against the background of aminasin. It may be concluded that while a prolonged injection of MSH results in the stimulation of the thyroid gland, the administration of the hormone in question against the background of aminasin results in the same ultramorphological structural changes of the gland which are observed after injection of aminasin alone, causing a decreased functional activity of the thyroid gland. The effect of intermedin upon the thyroid is supposed to be realized through those hypothalamus structures which are responsible for the regulation of the thyrotropic function of the hypophysis.", "contents": "[Changes in the thyrocytes to the administration of intermedin under conditions of the aminazine-altered functional state of the nervous system]. Histological and electron microscopial investigations of the thyroid gland were performed in white mice after exogeneous administration of intermedin (MSH) and intermedin against the background of aminasin. It may be concluded that while a prolonged injection of MSH results in the stimulation of the thyroid gland, the administration of the hormone in question against the background of aminasin results in the same ultramorphological structural changes of the gland which are observed after injection of aminasin alone, causing a decreased functional activity of the thyroid gland. The effect of intermedin upon the thyroid is supposed to be realized through those hypothalamus structures which are responsible for the regulation of the thyrotropic function of the hypophysis."} {"id": "PMID:1259608", "title": "[Histological aspects of posttraumatic regeneration].", "content": "A number of histological aspects (regeneration capacity, origins of regeneration, means of reparation) are discussed on the example of the reparative regeneration of the adrenal cortex. The adrenal cortex is found to possess high regeneration capacity after a traumatic injury of the organ. Realization of this capacity is dependent on general and local conditions, the character and the volume of the injury and the degree of involvment of cambial zones being of substantial significance. Among these zones are the glomerular zone and the external part of the bundle zone, whose proliferating cells are the source of the reparative regeneration of the cortical substance. The reparation of the functioning mass of the adrenal cortex is performed by the type of regenerative hypertrophy or the reparative regeneration depending on the character of the trauma. After the first type, the division of cells and their differentiation occur within the limits of the available structural elements, after the second type- of the newly formed ones. Both types are evolutionally conditioned and are definitely similar eather to postnatal growth and physiological regeneration (regenerative hypertrophy), or to the embryonic histogenesis of the definitive adrenal cortex (reparative regeneration).", "contents": "[Histological aspects of posttraumatic regeneration]. A number of histological aspects (regeneration capacity, origins of regeneration, means of reparation) are discussed on the example of the reparative regeneration of the adrenal cortex. The adrenal cortex is found to possess high regeneration capacity after a traumatic injury of the organ. Realization of this capacity is dependent on general and local conditions, the character and the volume of the injury and the degree of involvment of cambial zones being of substantial significance. Among these zones are the glomerular zone and the external part of the bundle zone, whose proliferating cells are the source of the reparative regeneration of the cortical substance. The reparation of the functioning mass of the adrenal cortex is performed by the type of regenerative hypertrophy or the reparative regeneration depending on the character of the trauma. After the first type, the division of cells and their differentiation occur within the limits of the available structural elements, after the second type- of the newly formed ones. Both types are evolutionally conditioned and are definitely similar eather to postnatal growth and physiological regeneration (regenerative hypertrophy), or to the embryonic histogenesis of the definitive adrenal cortex (reparative regeneration)."} {"id": "PMID:1259609", "title": "[Melatonin synthesis in enterochromaffin cells].", "content": "An active synthesis of melatonin which formerly was considered as a specific hormon of the epophysis, in the enterochromaffin cells of the gastro-intestinal tract was demonstrated using a combination of histochemical, biochemical and physiological methods. Biosynthesis of melatonin and serotonin by pinealocytes of the epiphysis and by enterochromaffin cells justifies the inclusion of them into one functional active neuro-endocrine cellular system playing a very important role in the maintaining of homeostasis of the organism.", "contents": "[Melatonin synthesis in enterochromaffin cells]. An active synthesis of melatonin which formerly was considered as a specific hormon of the epophysis, in the enterochromaffin cells of the gastro-intestinal tract was demonstrated using a combination of histochemical, biochemical and physiological methods. Biosynthesis of melatonin and serotonin by pinealocytes of the epiphysis and by enterochromaffin cells justifies the inclusion of them into one functional active neuro-endocrine cellular system playing a very important role in the maintaining of homeostasis of the organism."} {"id": "PMID:1259610", "title": "[A morphologic analysis of the manifestations of the effects of myelotransplantation].", "content": "The positive direct curative effect of grafting of the bone marrow in aplastic conditions of hemopoiesis is associated with rapid restoration of the myeloid tissue. Normalization of the hemopoiesis organs of recipients depends on the cellular mechanism of action of transplanted hemopoietic cells and a humoral stimulating effect of life-activity products of the survived transplanted cells. Widespread application of transplantation of allogenic heterologous bone marrow under clinical conditions is hindered by the development of secondary disease, frequently fatal for recipients. The major part of morphological changes in secondary disease are non-specific. Pathologo-anatomic diagnosis of chronic secondary disease may be established only with due regard for a compex analysis of the measures applied, clinical, hematological, immunological and morphological data.", "contents": "[A morphologic analysis of the manifestations of the effects of myelotransplantation]. The positive direct curative effect of grafting of the bone marrow in aplastic conditions of hemopoiesis is associated with rapid restoration of the myeloid tissue. Normalization of the hemopoiesis organs of recipients depends on the cellular mechanism of action of transplanted hemopoietic cells and a humoral stimulating effect of life-activity products of the survived transplanted cells. Widespread application of transplantation of allogenic heterologous bone marrow under clinical conditions is hindered by the development of secondary disease, frequently fatal for recipients. The major part of morphological changes in secondary disease are non-specific. Pathologo-anatomic diagnosis of chronic secondary disease may be established only with due regard for a compex analysis of the measures applied, clinical, hematological, immunological and morphological data."} {"id": "PMID:1259611", "title": "[Ultrastructural changes in the myocardial capillaries of rats following local irradiation of the heart region].", "content": "It was shown that single irradiation of the heart region in rats in doses 600, 900 and 2000 r could bring about congestion phenomena in the myocardium blood capillaries and drastic destructive alterations in the endothelial cells; these changes were noted in all time periods under study following the exposure (2 hr., 1, 5, 10 days, 1, 3, 6 and 12 months) the gravity of lesions being directly proportional to the dose rate. Irradiation led to the breakdown of the integrity of the endothelial wall due to formation of defects and delatation of the intercellular fissures, which results in a considerable rise in permeability. Due to perish of some part of capillaries diminishing of the capillary bed of the myocardium took place, particularly in remote periods. The irradiated animals showed an intensive overgrowth of the connective-tissue stroma in the intercellular and pericapillary spaces.", "contents": "[Ultrastructural changes in the myocardial capillaries of rats following local irradiation of the heart region]. It was shown that single irradiation of the heart region in rats in doses 600, 900 and 2000 r could bring about congestion phenomena in the myocardium blood capillaries and drastic destructive alterations in the endothelial cells; these changes were noted in all time periods under study following the exposure (2 hr., 1, 5, 10 days, 1, 3, 6 and 12 months) the gravity of lesions being directly proportional to the dose rate. Irradiation led to the breakdown of the integrity of the endothelial wall due to formation of defects and delatation of the intercellular fissures, which results in a considerable rise in permeability. Due to perish of some part of capillaries diminishing of the capillary bed of the myocardium took place, particularly in remote periods. The irradiated animals showed an intensive overgrowth of the connective-tissue stroma in the intercellular and pericapillary spaces."} {"id": "PMID:1259612", "title": "[Morphologic features of pneumonia in young children of the Northeast USSR].", "content": "Post-mortem investigations of the lungs of 160 children below 2 years of age who had died of acute pneumonia in Magadan were carried out with the use of histological, histochemical, histotopographic, macro- and micromorphometric methods. As to duration of the disease, pneumonias were divided arbitrarily into acute (up to 21 days) and protracted one (from 3 weeks to 2 months). It was established that acute pneumonia in children in Magadan were of polysegmentary character, with involvement in the process of 3-7 segments of each lung and with exclusion from the act of breathing up to 80-90% of the lung's surface. Most often the pathological process was localized in the posterior and postero-inferior segments. Along with pneumonia, which was of interstitial, focal or mixed character, atelectasis and acute emphysema developed. Histologically described acute pneumonias were characterized by pronounced lesions of the tracheobronchial tree, drastic circulatory disorders with formation of \"garland-like\" structures from the expanded capillary network of the lungs, the presence of hyaline membranes and large hyperchromic conglomerates. In protracted pneumonias in addition lesions of the argyrophilic and elastic carcass of the lungs were observed.", "contents": "[Morphologic features of pneumonia in young children of the Northeast USSR]. Post-mortem investigations of the lungs of 160 children below 2 years of age who had died of acute pneumonia in Magadan were carried out with the use of histological, histochemical, histotopographic, macro- and micromorphometric methods. As to duration of the disease, pneumonias were divided arbitrarily into acute (up to 21 days) and protracted one (from 3 weeks to 2 months). It was established that acute pneumonia in children in Magadan were of polysegmentary character, with involvement in the process of 3-7 segments of each lung and with exclusion from the act of breathing up to 80-90% of the lung's surface. Most often the pathological process was localized in the posterior and postero-inferior segments. Along with pneumonia, which was of interstitial, focal or mixed character, atelectasis and acute emphysema developed. Histologically described acute pneumonias were characterized by pronounced lesions of the tracheobronchial tree, drastic circulatory disorders with formation of \"garland-like\" structures from the expanded capillary network of the lungs, the presence of hyaline membranes and large hyperchromic conglomerates. In protracted pneumonias in addition lesions of the argyrophilic and elastic carcass of the lungs were observed."} {"id": "PMID:1259613", "title": "[Morphologic correlations of changes in the skeletal muscles and kidneys in several variants of the myorenal syndrome].", "content": "In 18 section observations of the myorenal syndrome (grave trauma, crash-syndrome, nontraumatic mascular ischemia) in skeletal muscles and the kidneys were investigated. In the skeletal muscles necrobiosis, necrosis with subsequent lysis or calcification of their sarcoplasm, edema of the intermuscular layers with subsequent multiplication of the stroma cells were noted. The kidneys revealed changes typical of a grave acute renal insufficiency. Ischemia of the cortex with atelectasis of glomerular capillaries and their increased permeability were evident. In the proximal tubules there were detected dystrophic changes of the type of granular degeneration and pronounced edema, these changes showing no tendency to reverse development and precluding regeneration of the epithelium. Acute renal insufficiency is closely connected with deep cortical blood flow reduction, the latter acting like a trigger.", "contents": "[Morphologic correlations of changes in the skeletal muscles and kidneys in several variants of the myorenal syndrome]. In 18 section observations of the myorenal syndrome (grave trauma, crash-syndrome, nontraumatic mascular ischemia) in skeletal muscles and the kidneys were investigated. In the skeletal muscles necrobiosis, necrosis with subsequent lysis or calcification of their sarcoplasm, edema of the intermuscular layers with subsequent multiplication of the stroma cells were noted. The kidneys revealed changes typical of a grave acute renal insufficiency. Ischemia of the cortex with atelectasis of glomerular capillaries and their increased permeability were evident. In the proximal tubules there were detected dystrophic changes of the type of granular degeneration and pronounced edema, these changes showing no tendency to reverse development and precluding regeneration of the epithelium. Acute renal insufficiency is closely connected with deep cortical blood flow reduction, the latter acting like a trigger."} {"id": "PMID:1259614", "title": "[Several clinic-morphologic aspects and problems concerning the pathogenesis of the Marchiafava-Miche li syndrome (paroxysmal nocturnal hemoglobinuria].", "content": "The authors present a broad pathoanatomic picture and concise clinical-laboratory characteristics of Marchiafava-Micheli's disease on the basis of their studies of case record date of 31 patients, data of 13 autopsies and findings of 27 treanobiopsies. Changes in the organs observed in Marchiafava-Micheli's disease were first of all morphological manifestations of massive intravascular hemolysis and associated with latter complications The most characteristic pathoanatomic feature was changes in the bone marrow which manifested themselves in hyperplasis of nuclear forms of the red series and in drastically pronounced disorders of the microcirculation. Necrobiotic changes in the kidney accompanied by massive hemosiderosis, dystrophic changes in the liver with the development of cirrhosis, inhibition of lymphopoiesiis in the spleen and lymph nodes were detected most often...", "contents": "[Several clinic-morphologic aspects and problems concerning the pathogenesis of the Marchiafava-Miche li syndrome (paroxysmal nocturnal hemoglobinuria]. The authors present a broad pathoanatomic picture and concise clinical-laboratory characteristics of Marchiafava-Micheli's disease on the basis of their studies of case record date of 31 patients, data of 13 autopsies and findings of 27 treanobiopsies. Changes in the organs observed in Marchiafava-Micheli's disease were first of all morphological manifestations of massive intravascular hemolysis and associated with latter complications The most characteristic pathoanatomic feature was changes in the bone marrow which manifested themselves in hyperplasis of nuclear forms of the red series and in drastically pronounced disorders of the microcirculation. Necrobiotic changes in the kidney accompanied by massive hemosiderosis, dystrophic changes in the liver with the development of cirrhosis, inhibition of lymphopoiesiis in the spleen and lymph nodes were detected most often..."} {"id": "PMID:1259615", "title": "[Morphologic reflection of protein biosynthesis disorders in the myocardial cells of rabbits with acute diphtheritic intoxication].", "content": "The lethal dose of diphtheria toxin (IDLM per 1 kg of body weight) was injected to Chinchilla line adult rabbits. Histological and electron-microscopy investigations were carried out in time periods from 3 to 24 hours following the administration of the toxin. Degenerative and necrotic changes in the myocardial cells under conditions of the given experiment were not observed. In many muscular cells dilatation of the perinuclear spaces due to the thinning of the myofibrila layer moved to the periphery of the cell was noted. Electron-microscopy investigation of the perinuclear spaces showed a decrease in the number of mitochondria, reduction of the elements of sarcoplasmatic reticulum and disappearance of ribosomes. Cytochemically, in the opened cytoplasmatic matrix there were revealed numerous beta-granules of glycogen. In nuclei fragmentation of nucleoli with reduction of their granular component was observed. The changes described justify the conclusion that acute diphtheria intoxication at early stages of exposure to the toxin brings about impairment of the protein synthesis not only at the level of translation on cytoplasmatic ribosomes, as was suggested before, but at the level of ribosome formation in the nucleus as well.", "contents": "[Morphologic reflection of protein biosynthesis disorders in the myocardial cells of rabbits with acute diphtheritic intoxication]. The lethal dose of diphtheria toxin (IDLM per 1 kg of body weight) was injected to Chinchilla line adult rabbits. Histological and electron-microscopy investigations were carried out in time periods from 3 to 24 hours following the administration of the toxin. Degenerative and necrotic changes in the myocardial cells under conditions of the given experiment were not observed. In many muscular cells dilatation of the perinuclear spaces due to the thinning of the myofibrila layer moved to the periphery of the cell was noted. Electron-microscopy investigation of the perinuclear spaces showed a decrease in the number of mitochondria, reduction of the elements of sarcoplasmatic reticulum and disappearance of ribosomes. Cytochemically, in the opened cytoplasmatic matrix there were revealed numerous beta-granules of glycogen. In nuclei fragmentation of nucleoli with reduction of their granular component was observed. The changes described justify the conclusion that acute diphtheria intoxication at early stages of exposure to the toxin brings about impairment of the protein synthesis not only at the level of translation on cytoplasmatic ribosomes, as was suggested before, but at the level of ribosome formation in the nucleus as well."} {"id": "PMID:1259616", "title": "[A histotopographic study of the pancreas in lipomatosis].", "content": "Histotopographic investigations of the pancreas in lipomatosis were carried out and results obtained were collated with clinical data. It was established that diminution of the exocrine parenchyma in this case may be quite considerable-in some cases only 9.9-12% of its amount remained. Despite the considerable diminishing of the exocrine parenchyma in lipomatosis, no clinical manifestations of the disorder of the exocrine function may be observed. Experimental data showed that loss of the exocrine parenchyma of the pancreas may be compensated in other parts of the gastro-intestinal tract, in the stomach in particular.", "contents": "[A histotopographic study of the pancreas in lipomatosis]. Histotopographic investigations of the pancreas in lipomatosis were carried out and results obtained were collated with clinical data. It was established that diminution of the exocrine parenchyma in this case may be quite considerable-in some cases only 9.9-12% of its amount remained. Despite the considerable diminishing of the exocrine parenchyma in lipomatosis, no clinical manifestations of the disorder of the exocrine function may be observed. Experimental data showed that loss of the exocrine parenchyma of the pancreas may be compensated in other parts of the gastro-intestinal tract, in the stomach in particular."} {"id": "PMID:1259617", "title": "[Chronic primary tuberculosis disguised as asthmatic bronchitis].", "content": "An observation over a chronic course of primary tuberculosis of the lung in a 78-year-old female patient with involvement of the perihilar lymph nodes, development of periadenitis, ingrowth of tuberculous granulations into the lumen of bronchi and with formation of fistulas is described. Clinically the disease proceeded as asthmatic bronchitis.", "contents": "[Chronic primary tuberculosis disguised as asthmatic bronchitis]. An observation over a chronic course of primary tuberculosis of the lung in a 78-year-old female patient with involvement of the perihilar lymph nodes, development of periadenitis, ingrowth of tuberculous granulations into the lumen of bronchi and with formation of fistulas is described. Clinically the disease proceeded as asthmatic bronchitis."} {"id": "PMID:1259618", "title": "[Determination of the quantity of cells in different organs and tissues following alkaline dissociation].", "content": "A tissue following fixation for 10-15 days with formalin was treated with 50% KOH aqueous solution during 18 hours, which led to complete dissociation of the tissue into cells. Suspension of cells was placed into the counter of Fuchs-Rosenthal and numbers of nuclei in cells of definite tissues were counted. On preparations of the same suspension in 1000 cells distribution of the latter according to the number of nuclei was determined. Then a number of cells in 1 mg of tissue and in the organ were estimated. The count of muscular cells in the heart of a mouse showed that the relative error of the determination of the number of cells did not exceed 2.0%.", "contents": "[Determination of the quantity of cells in different organs and tissues following alkaline dissociation]. A tissue following fixation for 10-15 days with formalin was treated with 50% KOH aqueous solution during 18 hours, which led to complete dissociation of the tissue into cells. Suspension of cells was placed into the counter of Fuchs-Rosenthal and numbers of nuclei in cells of definite tissues were counted. On preparations of the same suspension in 1000 cells distribution of the latter according to the number of nuclei was determined. Then a number of cells in 1 mg of tissue and in the organ were estimated. The count of muscular cells in the heart of a mouse showed that the relative error of the determination of the number of cells did not exceed 2.0%."} {"id": "PMID:1259630", "title": "[Electromyographic and neurological aspects of leprosy. Study of 100 cases].", "content": "By the neurological, electromyographic, anatomopathological and bacterioscopic examinations of 100 pacients with leprosy the following conclusions have been drawn: There was a high incidence of reflex abnormalities. The proprioceptive reflexes were abnormal in 64.5% and the superficial reflexes in 70.8% of the cases. According to the topography of the segments examined, the deep reflexes showed the following abnormal values: 25.3% in the cephalic segment; 69.1% in the upper limbs and 74.5% in the lower limbs. Of the 2,289 reflexes investigated, abnormalities were found in 773 superficial reflexes (70.8%), while in relation to the proprioceptive reflexes the figures rose to 901 (64.5%). In the early stages of the infirmity, the reflexes were normal in 41.2% of the cases examined, and in all the stages of the evolution of the disease those numbers were always high. Also in the first stage, whose average duration was of 4.9 years, several alternations were noted, although there was a predominance of brisk reflexes (25.1%) over diminshed reflexes (17%), followed by hyperactive (8.6%) and absent reflexes (8%). In the final stage of the infirmity there was a decrease of normal reflexes, in contrast to absent and decreased reflexes, whose rates increased to 32.7% and 30.6% respectively. The disappearance of hyperactive reflexes and the clear decrease of brisk reflexes should also be noted. There was a high percentage of patients (31%) who suffered agression of the eighth nerve, 17 of which (54.8%) were found to suffer from neural deafness. The values related to hearing deficit were rarely in accordance with the histopathological and bacterioscopic positive results. The indexes of abnormalities found out in the examination of the fifth and of the seven nerve (7% and 5% respectively) were much lower in relation to the eighth nerve. These results are in contradiction with the ones stated in the literature. In some of the patients, hyperesthesia of the skin of the plantar region prognosticated the appearance of the infirmity. Among the objective changes, anesthesia of superficial sensibilities combined with deep hyperesthesia and anesthesia of superficial sensibilities with abolition of profound sensibilities were rarely observed. No case was found with exclusive alterations of deep sensibilities. Peripheral motor neuron lesions demonstrable by electromyography were observed in 82 patients (82%)...", "contents": "[Electromyographic and neurological aspects of leprosy. Study of 100 cases]. By the neurological, electromyographic, anatomopathological and bacterioscopic examinations of 100 pacients with leprosy the following conclusions have been drawn: There was a high incidence of reflex abnormalities. The proprioceptive reflexes were abnormal in 64.5% and the superficial reflexes in 70.8% of the cases. According to the topography of the segments examined, the deep reflexes showed the following abnormal values: 25.3% in the cephalic segment; 69.1% in the upper limbs and 74.5% in the lower limbs. Of the 2,289 reflexes investigated, abnormalities were found in 773 superficial reflexes (70.8%), while in relation to the proprioceptive reflexes the figures rose to 901 (64.5%). In the early stages of the infirmity, the reflexes were normal in 41.2% of the cases examined, and in all the stages of the evolution of the disease those numbers were always high. Also in the first stage, whose average duration was of 4.9 years, several alternations were noted, although there was a predominance of brisk reflexes (25.1%) over diminshed reflexes (17%), followed by hyperactive (8.6%) and absent reflexes (8%). In the final stage of the infirmity there was a decrease of normal reflexes, in contrast to absent and decreased reflexes, whose rates increased to 32.7% and 30.6% respectively. The disappearance of hyperactive reflexes and the clear decrease of brisk reflexes should also be noted. There was a high percentage of patients (31%) who suffered agression of the eighth nerve, 17 of which (54.8%) were found to suffer from neural deafness. The values related to hearing deficit were rarely in accordance with the histopathological and bacterioscopic positive results. The indexes of abnormalities found out in the examination of the fifth and of the seven nerve (7% and 5% respectively) were much lower in relation to the eighth nerve. These results are in contradiction with the ones stated in the literature. In some of the patients, hyperesthesia of the skin of the plantar region prognosticated the appearance of the infirmity. Among the objective changes, anesthesia of superficial sensibilities combined with deep hyperesthesia and anesthesia of superficial sensibilities with abolition of profound sensibilities were rarely observed. No case was found with exclusive alterations of deep sensibilities. Peripheral motor neuron lesions demonstrable by electromyography were observed in 82 patients (82%)..."} {"id": "PMID:1259631", "title": "Cervical spondylosis. Prognostic value of preoperative signs and symptoms.", "content": "One hundred and forty-one patients with cervical spondylosis were studied, looking for a possible prognostic value in preoperative signs and symptoms. Duration of symptoms lasting from one month to five years until surgical treatment and spinal fluid protein level had no prognostic value in these patients. In those with radiculopathy, the degree of upper limb pareses, muscle atrophy, absent or diminished reflexes, sensory involvement, number of myelographic defects and age had prognostic value. In those with myelopathy, the degree of lower limbs pareses and spasticity, sensory involvement, number of myelographic defects and age had prognostic value. Surgery is a definite method of treatment for patients with progressive signs and symptoms due to cervical spondylosis; some of the preoperative signs and symptoms are valuable in establishing their prognosis.", "contents": "Cervical spondylosis. Prognostic value of preoperative signs and symptoms. One hundred and forty-one patients with cervical spondylosis were studied, looking for a possible prognostic value in preoperative signs and symptoms. Duration of symptoms lasting from one month to five years until surgical treatment and spinal fluid protein level had no prognostic value in these patients. In those with radiculopathy, the degree of upper limb pareses, muscle atrophy, absent or diminished reflexes, sensory involvement, number of myelographic defects and age had prognostic value. In those with myelopathy, the degree of lower limbs pareses and spasticity, sensory involvement, number of myelographic defects and age had prognostic value. Surgery is a definite method of treatment for patients with progressive signs and symptoms due to cervical spondylosis; some of the preoperative signs and symptoms are valuable in establishing their prognosis."} {"id": "PMID:1259632", "title": "Cerebrospinal fluid immunoglobulins in cysticercosis of the central nervous system.", "content": "Investigation on the behavior of immunoglobulins IGG, IGA and IGM in the CSF in cases of cysticercosis of the CNS, based on data pertaining to two different series of cases. The first series comprises 30 samples of CSF, and the second one, 5 samples. It was demonstrated that IGG is the one representing the largest contingent. IGG concentration keeps in proportion with the gamma globulin concentration, of which it represented an 88% average in the cases studied. Participation of IGG in the protein profile of the CSF is greater than the usually referred; the results for the material analyzed showed 16%. It was verified a proporcionality also between IGG concentration and the titer of positive complement fixation test for cysticercosis; there is a positive correlation, whose numerical expression was found to be significant in the samples studied.", "contents": "Cerebrospinal fluid immunoglobulins in cysticercosis of the central nervous system. Investigation on the behavior of immunoglobulins IGG, IGA and IGM in the CSF in cases of cysticercosis of the CNS, based on data pertaining to two different series of cases. The first series comprises 30 samples of CSF, and the second one, 5 samples. It was demonstrated that IGG is the one representing the largest contingent. IGG concentration keeps in proportion with the gamma globulin concentration, of which it represented an 88% average in the cases studied. Participation of IGG in the protein profile of the CSF is greater than the usually referred; the results for the material analyzed showed 16%. It was verified a proporcionality also between IGG concentration and the titer of positive complement fixation test for cysticercosis; there is a positive correlation, whose numerical expression was found to be significant in the samples studied."} {"id": "PMID:1259633", "title": "Copper and ceruloplasmin contents in the blood serum of peripheral and pre-hepatic veins.", "content": "Cooper and ceruloplasmin contents were determined in samples of peripheral and pre-hepatic venous blood of 11 patients with Manson's schistosomiasis and one patient with hepatolenticular degeneration, all of \u00e7hich submitted either to porto-caval or spleno-renal shunt. Individual difference were not significant in any of the non-Wilsonian patients. The results are discussed in regard to the current knowledge on the pathogenesis of Wilson's disease.", "contents": "Copper and ceruloplasmin contents in the blood serum of peripheral and pre-hepatic veins. Cooper and ceruloplasmin contents were determined in samples of peripheral and pre-hepatic venous blood of 11 patients with Manson's schistosomiasis and one patient with hepatolenticular degeneration, all of \u00e7hich submitted either to porto-caval or spleno-renal shunt. Individual difference were not significant in any of the non-Wilsonian patients. The results are discussed in regard to the current knowledge on the pathogenesis of Wilson's disease."} {"id": "PMID:1259634", "title": "[Inflammatory chronic processes of the central nervous system. Neurosurgical aspects].", "content": "A study into the neurosurgical approach to thirty-five patients with increased intracranial pressure due to inflamatory diseases affecting the central nervous system and meninges is reported. The entitites under consideration were found to have similar surgical aspects despite the heterogeneity of etiologic agents. As regards the surgical treatment, two groups of cases were recognized. Group 1 comprises 7 patientes with symptoms of a space-occupying lesion; in these patients craniotomies were performed with good results. Group 2 included the remainder 28 cases with acquired hydrocephalus. In this group differents methods for ventricular drainage were used, but ventriculo-auriculostomy and specially ventriculo-peritoneal shunts proved to give more gratifying results. Chemotherapy was administred when the etiologic agent was disclosed. Corticosteroids were institued to reduce inflammatory reations and cerebral edema. A review of the literature supported the practical classification and surgical techniques employed.", "contents": "[Inflammatory chronic processes of the central nervous system. Neurosurgical aspects]. A study into the neurosurgical approach to thirty-five patients with increased intracranial pressure due to inflamatory diseases affecting the central nervous system and meninges is reported. The entitites under consideration were found to have similar surgical aspects despite the heterogeneity of etiologic agents. As regards the surgical treatment, two groups of cases were recognized. Group 1 comprises 7 patientes with symptoms of a space-occupying lesion; in these patients craniotomies were performed with good results. Group 2 included the remainder 28 cases with acquired hydrocephalus. In this group differents methods for ventricular drainage were used, but ventriculo-auriculostomy and specially ventriculo-peritoneal shunts proved to give more gratifying results. Chemotherapy was administred when the etiologic agent was disclosed. Corticosteroids were institued to reduce inflammatory reations and cerebral edema. A review of the literature supported the practical classification and surgical techniques employed."} {"id": "PMID:1259635", "title": "[Ferruginated neurons in cerebral infarcts].", "content": "The study of the ferruginated neurons in the analysis of 87 cases of cerebral infarcts is reported. The lesion found in 40,3% of the cases was demonstrared to contain iron and calcium. It was found to be more frequent in older patients and predominantly in the cortical necrotic areas. The minerals were also detected in basophilic granules found outside the cells in the necrotic tissue. There was no correlation with the basic disease, although in 17% of the cases there was an association with sickling of the red blood cells. The role of the mineral content of the nervous tissue in the pathogenesis of the incrustation is discussed. The demonstration of other minerals besides the iron in the cells makes the term \"mineralization of neurons\" more acceptable.", "contents": "[Ferruginated neurons in cerebral infarcts]. The study of the ferruginated neurons in the analysis of 87 cases of cerebral infarcts is reported. The lesion found in 40,3% of the cases was demonstrared to contain iron and calcium. It was found to be more frequent in older patients and predominantly in the cortical necrotic areas. The minerals were also detected in basophilic granules found outside the cells in the necrotic tissue. There was no correlation with the basic disease, although in 17% of the cases there was an association with sickling of the red blood cells. The role of the mineral content of the nervous tissue in the pathogenesis of the incrustation is discussed. The demonstration of other minerals besides the iron in the cells makes the term \"mineralization of neurons\" more acceptable."} {"id": "PMID:1259636", "title": "[Hereditary proximal neurogenic muscular atrophy (Wohlfart-Kugelberg-Welander disease). Electromyographic, anatomo-pathologic and clinical study in 3 brothers].", "content": "The cases of three brothers with proximal weakness and muscles atrophies beginning in childhood are reported. Muscles biopsies and electromyographic studies have shown neurogenic pattern of atrophy and a dystrophy-like picture. It is concluded that this histological and eletromyographic picture can occur in pure partial denervation of long standing. The histopathologic study of the spinal cord of one patient revealed degenerative changes and loss of anterior horn ganglion cells. This is the fourth case of Wohlfar-Kugelberg-Welander disease with postmortem examination.", "contents": "[Hereditary proximal neurogenic muscular atrophy (Wohlfart-Kugelberg-Welander disease). Electromyographic, anatomo-pathologic and clinical study in 3 brothers]. The cases of three brothers with proximal weakness and muscles atrophies beginning in childhood are reported. Muscles biopsies and electromyographic studies have shown neurogenic pattern of atrophy and a dystrophy-like picture. It is concluded that this histological and eletromyographic picture can occur in pure partial denervation of long standing. The histopathologic study of the spinal cord of one patient revealed degenerative changes and loss of anterior horn ganglion cells. This is the fourth case of Wohlfar-Kugelberg-Welander disease with postmortem examination."} {"id": "PMID:1259637", "title": "A model for familial trends in oligophrenia.", "content": "Theories and evidences on etiology of mental retardation are presented. Five cases of mental retardation from a Clinical Genetics Service are reported, as basis for an etiological model on mental retardation, quite operational in genetic counseling and familial orientation.", "contents": "A model for familial trends in oligophrenia. Theories and evidences on etiology of mental retardation are presented. Five cases of mental retardation from a Clinical Genetics Service are reported, as basis for an etiological model on mental retardation, quite operational in genetic counseling and familial orientation."} {"id": "PMID:1259638", "title": "[Bilateral facial paralysis].", "content": "A case of bilateral facial paralysis following meningococcal meningitis and herpes simplex infection is reported. The author discusses the differential diagnosis of bilateral facial nerve paralysis which included several diseases and syndromes and concludes by herpetic aetiology.", "contents": "[Bilateral facial paralysis]. A case of bilateral facial paralysis following meningococcal meningitis and herpes simplex infection is reported. The author discusses the differential diagnosis of bilateral facial nerve paralysis which included several diseases and syndromes and concludes by herpetic aetiology."} {"id": "PMID:1259640", "title": "Cerebral embolism, marantic endocarditis, and cancer.", "content": "Two subjects with cerebral embolism were found at autopsy to have marantic (nonbacterial thrombotic) endocarditis (NBTE) and an unsuspected carcinoma. A additional 16 subjects with marantic endocarditis and cancer were found on reviewing the autopsy records of 22 subjects with NBTE. Of these 18 subjects with NBTE and cancer, eight developed a stroke during their illness, in five as the initial manifestation of cancer. Although the association of cancer and marantic endocarditis is generally well recognized, cerebral embolism from this source should be more seriously considered as one of the \"remote effects\" of cancer on the nervous system.", "contents": "Cerebral embolism, marantic endocarditis, and cancer. Two subjects with cerebral embolism were found at autopsy to have marantic (nonbacterial thrombotic) endocarditis (NBTE) and an unsuspected carcinoma. A additional 16 subjects with marantic endocarditis and cancer were found on reviewing the autopsy records of 22 subjects with NBTE. Of these 18 subjects with NBTE and cancer, eight developed a stroke during their illness, in five as the initial manifestation of cancer. Although the association of cancer and marantic endocarditis is generally well recognized, cerebral embolism from this source should be more seriously considered as one of the \"remote effects\" of cancer on the nervous system."} {"id": "PMID:1259641", "title": "Reduced plasma norepinephrine response to standing in autonomic dysfunction.", "content": "In five patients having primary autonomic dysfunction with clinical manifestations including postural hypotension, the mean plasma norepinephrine concentrations were significantly lower than those of normal subjects after two and five minutes in the standing position. The mean (+/-SE) increment in the plasma norepinephrine concentration after two minutes standing were 123 +/- 19 pg/ml in the normal subjects and 13 +/- 4 pg/ml (P less than .001) in the patients with primary autonomic dysfunction. After five minutes standing, the mean increment in plasma norepinephrine concentration was 244 +/- 36 pg/ml in the normal subjects and 99 +/- 51 pg/ml (P less than .05) in the patients. There were no statistically significant differences in plasma epinephrine between the two groups.", "contents": "Reduced plasma norepinephrine response to standing in autonomic dysfunction. In five patients having primary autonomic dysfunction with clinical manifestations including postural hypotension, the mean plasma norepinephrine concentrations were significantly lower than those of normal subjects after two and five minutes in the standing position. The mean (+/-SE) increment in the plasma norepinephrine concentration after two minutes standing were 123 +/- 19 pg/ml in the normal subjects and 13 +/- 4 pg/ml (P less than .001) in the patients with primary autonomic dysfunction. After five minutes standing, the mean increment in plasma norepinephrine concentration was 244 +/- 36 pg/ml in the normal subjects and 99 +/- 51 pg/ml (P less than .05) in the patients. There were no statistically significant differences in plasma epinephrine between the two groups."} {"id": "PMID:1259642", "title": "Symptoms of pheochromocytoma, with particular reference to headache, correlated with catecholamine production.", "content": "In a series of 27 patients with proved pheochromocytoma, differential analysis of catecholamines in blood, urine, and tumor specimens of 19 patients enabled grouping of subjects into those whose tumors produced predominantly norepinephrine (NE) (11 patients), predominantly epinephrine (E [Two patients]) and approximately equal amounts of both (six patients). Sustained hypertension was more common in the first group and pallor and tremor in the latter two groups, but no distinctive syndrome could be recognized as signifying the secretion of NE or E. Headache was a symptom in 20 of 27 patients and was related to sudden, transient elevation of the blood pressure, rather than sustained hypertension. The variable duration and intensity of the headache in different patients can be explained by the pressor and cranial vasoconstrictor effects of the secreted amines, which respectively enhance and diminish vascular headache.", "contents": "Symptoms of pheochromocytoma, with particular reference to headache, correlated with catecholamine production. In a series of 27 patients with proved pheochromocytoma, differential analysis of catecholamines in blood, urine, and tumor specimens of 19 patients enabled grouping of subjects into those whose tumors produced predominantly norepinephrine (NE) (11 patients), predominantly epinephrine (E [Two patients]) and approximately equal amounts of both (six patients). Sustained hypertension was more common in the first group and pallor and tremor in the latter two groups, but no distinctive syndrome could be recognized as signifying the secretion of NE or E. Headache was a symptom in 20 of 27 patients and was related to sudden, transient elevation of the blood pressure, rather than sustained hypertension. The variable duration and intensity of the headache in different patients can be explained by the pressor and cranial vasoconstrictor effects of the secreted amines, which respectively enhance and diminish vascular headache."} {"id": "PMID:1259643", "title": "Shy-Drager syndrome with abnormal respirations and antidiuretic hormone release.", "content": "A patient with Shy-Drager syndrome exhibited a partial defect in antidiuretic hormone (ADH) release, and cluster breathing, an indication of pontomedullary respiratory center damage, with a normal CO2 response curve. This extends the spectrum of abnormalities associated with the degenerative disease of the central nervous system. The presence of a pontomedullary respiratory pattern without an impaired CO2 response curve suggests that neurons that determine respiratory rhythm function independently from those that function as chemoreceptors.", "contents": "Shy-Drager syndrome with abnormal respirations and antidiuretic hormone release. A patient with Shy-Drager syndrome exhibited a partial defect in antidiuretic hormone (ADH) release, and cluster breathing, an indication of pontomedullary respiratory center damage, with a normal CO2 response curve. This extends the spectrum of abnormalities associated with the degenerative disease of the central nervous system. The presence of a pontomedullary respiratory pattern without an impaired CO2 response curve suggests that neurons that determine respiratory rhythm function independently from those that function as chemoreceptors."} {"id": "PMID:1259644", "title": "Drug-induced IgA deficiency in epileptic patients.", "content": "Serum concentrations of IgA, IgG, and IgM were determined by immunodiffusion technique in 184 epileptic patients and 95 healthy individuals. Twenty-one percent of adult and 42% of children patients receiving anticonvulsants had serum IgA levels below 0.6 mg/ml (the lowest value detected in normal sera). Serum concentrations in non-drug-taking epileptic patients were normal. Deviations in IgG/IgM concentrations were smaller and less consistent. Serum IgA level was determined at intervals before and during phenytoin treatments. A fall in the IgA level occurred in several patients. In two patients, IgA deficiency developed within two to three months of treatment. Low IgA-responders were more frequent among men and children. The IgA anomaly was not specific for any type of epilepsy.", "contents": "Drug-induced IgA deficiency in epileptic patients. Serum concentrations of IgA, IgG, and IgM were determined by immunodiffusion technique in 184 epileptic patients and 95 healthy individuals. Twenty-one percent of adult and 42% of children patients receiving anticonvulsants had serum IgA levels below 0.6 mg/ml (the lowest value detected in normal sera). Serum concentrations in non-drug-taking epileptic patients were normal. Deviations in IgG/IgM concentrations were smaller and less consistent. Serum IgA level was determined at intervals before and during phenytoin treatments. A fall in the IgA level occurred in several patients. In two patients, IgA deficiency developed within two to three months of treatment. Low IgA-responders were more frequent among men and children. The IgA anomaly was not specific for any type of epilepsy."} {"id": "PMID:1259645", "title": "Brain specialization for language does not depend on literacy.", "content": "Aphasia in focal brain-damaged illiterates is analogous to aphasia in patients who have learned how to read and write, regarding (1) expectancy rate, (2) distribution of clinical types, (3) semiological structure, and (4) score of relevant laboratory variables. The organization of neurological structures whose lesions produce language disturbances seems to be independent from the acquisition of reading and writing skills.", "contents": "Brain specialization for language does not depend on literacy. Aphasia in focal brain-damaged illiterates is analogous to aphasia in patients who have learned how to read and write, regarding (1) expectancy rate, (2) distribution of clinical types, (3) semiological structure, and (4) score of relevant laboratory variables. The organization of neurological structures whose lesions produce language disturbances seems to be independent from the acquisition of reading and writing skills."} {"id": "PMID:1259646", "title": "Infantile hemifacial spasm.", "content": "A 6-week-old infant had recurrent contractions of the facial musculature on the left side, which continued throughout early childhood. Surgical exploration at 5 1/2 years of age revealed a ganglioneuroma of the fourth ventricle. Hemifacial spasm (HFS) in infancy and childhood suggests the possibility of serious intracranial pathologic findings.", "contents": "Infantile hemifacial spasm. A 6-week-old infant had recurrent contractions of the facial musculature on the left side, which continued throughout early childhood. Surgical exploration at 5 1/2 years of age revealed a ganglioneuroma of the fourth ventricle. Hemifacial spasm (HFS) in infancy and childhood suggests the possibility of serious intracranial pathologic findings."} {"id": "PMID:1259655", "title": "Properties of non-neurovirulent plaque-forming mutants of Newcaslte disease virus.", "content": "The mesogenic Hertfordshire (H) strain, a vaccine strain of Newcastle disease virus, represents a heterogeneous virus population differing in physical, chemical, and biological properties. Small (S) and large (L) plaque-forming mutants were isolted from strain H in chick embryo fibroblast cell cultures. Part of the S mutants lacked neurovirulence, with an intracerebral pathogenicity index for day-old chicks of 0 to 0.46 vs 1.0 to 1.4 for L mutants. S mutants grew only to a very low titer in the brain of day-old chicks and cleared from the brain by the sixth day, whereas L mutants killed the chicks after a 1000-fold titer rise. The S mutants caused a complete cell destruction in fibroblast culture by 12 hours, but they had 10--20 times lower virus yields than the L mutants. The infective titers of S and L mutants grown in allantoic cells were identical, but the infectivity to hemagglutinin ratio was 10 to 50 times lower for S than for L. The thermostability of infectivity and hemagglutinin varied with the different mutants. As for the immunogenicity of the mutants, the minimum dose of S mutants inducing full protection by subcutaneous inoculation was 10(6) plaque-forming units per chicken, thus being about 100 times less immunogenic than either the L mutants or the parent strain H.", "contents": "Properties of non-neurovirulent plaque-forming mutants of Newcaslte disease virus. The mesogenic Hertfordshire (H) strain, a vaccine strain of Newcastle disease virus, represents a heterogeneous virus population differing in physical, chemical, and biological properties. Small (S) and large (L) plaque-forming mutants were isolted from strain H in chick embryo fibroblast cell cultures. Part of the S mutants lacked neurovirulence, with an intracerebral pathogenicity index for day-old chicks of 0 to 0.46 vs 1.0 to 1.4 for L mutants. S mutants grew only to a very low titer in the brain of day-old chicks and cleared from the brain by the sixth day, whereas L mutants killed the chicks after a 1000-fold titer rise. The S mutants caused a complete cell destruction in fibroblast culture by 12 hours, but they had 10--20 times lower virus yields than the L mutants. The infective titers of S and L mutants grown in allantoic cells were identical, but the infectivity to hemagglutinin ratio was 10 to 50 times lower for S than for L. The thermostability of infectivity and hemagglutinin varied with the different mutants. As for the immunogenicity of the mutants, the minimum dose of S mutants inducing full protection by subcutaneous inoculation was 10(6) plaque-forming units per chicken, thus being about 100 times less immunogenic than either the L mutants or the parent strain H."} {"id": "PMID:1259656", "title": "The presence of avian adenoviruses and adeno-associated viruses in healthy chickens.", "content": "Avian adenoviruses were isolated from 56 of 106 fecal and rectal tissue samples taken from apparently healthy young chickens on 4 farms. Only one isolation was made from the 37 samples from 3- and 4-week-old chicks, while the isolation frequency was 64-100% in groups 5 weeks old and older. The 56 adenovirus isolates were classified into 6 serotypes. Vurses of 3 or 4 types were found on each farm. Avian adeno-associated virus CF antigens were found, using chicken embryos coinfected with an adenovirus helper, in 2 of the 38 adenovirus isolated studied.", "contents": "The presence of avian adenoviruses and adeno-associated viruses in healthy chickens. Avian adenoviruses were isolated from 56 of 106 fecal and rectal tissue samples taken from apparently healthy young chickens on 4 farms. Only one isolation was made from the 37 samples from 3- and 4-week-old chicks, while the isolation frequency was 64-100% in groups 5 weeks old and older. The 56 adenovirus isolates were classified into 6 serotypes. Vurses of 3 or 4 types were found on each farm. Avian adeno-associated virus CF antigens were found, using chicken embryos coinfected with an adenovirus helper, in 2 of the 38 adenovirus isolated studied."} {"id": "PMID:1259657", "title": "Aerosol vaccination against Newcastle disease. I. Studies on particle size.", "content": "Studies revealed that the majority of particles emitted by three different aerosol generators were in the size ranges of 0.5-1 and 1-3 mum. In general, the smaller the aperture setting, the larger the total number of particles. The difference between the generators in number of particles emitted were not significant enough to produce appreciable difference in antibody titers obtained from vaccinated chickens. Antibody titers were higher in birds vaccinated with the LaSota strain of Newcastle disease virus than in birds vaccinated with the B-1 strain, although protection against challenge was approximately similar. Aerosol challenge was found as effective as intramuscular challenge.", "contents": "Aerosol vaccination against Newcastle disease. I. Studies on particle size. Studies revealed that the majority of particles emitted by three different aerosol generators were in the size ranges of 0.5-1 and 1-3 mum. In general, the smaller the aperture setting, the larger the total number of particles. The difference between the generators in number of particles emitted were not significant enough to produce appreciable difference in antibody titers obtained from vaccinated chickens. Antibody titers were higher in birds vaccinated with the LaSota strain of Newcastle disease virus than in birds vaccinated with the B-1 strain, although protection against challenge was approximately similar. Aerosol challenge was found as effective as intramuscular challenge."} {"id": "PMID:1259658", "title": "In vitro DNA synthesis in lymphocytes from turkeys vaccinated with LaSota, TC, and inactivated Newcastle disease vaccines.", "content": "In vitro cultures of peripheral blood lymphocytes from turkeys vaccinated and revaccinated with Newcastle disease (ND) vaccines were stimulated to transformation when exposed to the homologous and heterologous strains of ND virus. The mitogenesis was measured by the uptake of 3H-thymidine into newly synthesized DNA. There was considerable difference in DNA synthesis by lymphocytes drawn 0, 2, 5, and 10 days after vaccination and revaccination with the three vaccines. Stimulation of DNA synthesis, evident as early as the 2nd day, was highest in lymphocytes from turkeys vaccinated or revaccinated with TCND intramuscularly. Stimulation was least in lymphocytes from turkeys vaccinated and revaccinated with LaSota vaccine by aersol. Stimulation was intermediate from an inactivated vaccine given subcutaneously. DNA synthesis was greater with the homologous than with the heterologous strains of NDV. Synthesis was even greater when the same strain was used as a viral suspension in allantoic or cell-culture fluid than the commercial vaccine. The bovine paramyxovirus (PI3) resulted in a minimum DNA synthesis or completely inhibited it. A many-fold (order of magnitude) stimulatory effect was observed when PHA was used as an antigen. The stimulation of DNA synthesis did not parallel the HI antibody response.", "contents": "In vitro DNA synthesis in lymphocytes from turkeys vaccinated with LaSota, TC, and inactivated Newcastle disease vaccines. In vitro cultures of peripheral blood lymphocytes from turkeys vaccinated and revaccinated with Newcastle disease (ND) vaccines were stimulated to transformation when exposed to the homologous and heterologous strains of ND virus. The mitogenesis was measured by the uptake of 3H-thymidine into newly synthesized DNA. There was considerable difference in DNA synthesis by lymphocytes drawn 0, 2, 5, and 10 days after vaccination and revaccination with the three vaccines. Stimulation of DNA synthesis, evident as early as the 2nd day, was highest in lymphocytes from turkeys vaccinated or revaccinated with TCND intramuscularly. Stimulation was least in lymphocytes from turkeys vaccinated and revaccinated with LaSota vaccine by aersol. Stimulation was intermediate from an inactivated vaccine given subcutaneously. DNA synthesis was greater with the homologous than with the heterologous strains of NDV. Synthesis was even greater when the same strain was used as a viral suspension in allantoic or cell-culture fluid than the commercial vaccine. The bovine paramyxovirus (PI3) resulted in a minimum DNA synthesis or completely inhibited it. A many-fold (order of magnitude) stimulatory effect was observed when PHA was used as an antigen. The stimulation of DNA synthesis did not parallel the HI antibody response."} {"id": "PMID:1259654", "title": "Progressive changes in serum proteins and the rheumatoid factor of chickens infected with Mycoplasma synoviae.", "content": "Sera from controls and chickens infected with Mycoplasma synoviae were examined for serum protein content by cellulose-acetate electrophoresis, and for rheumatoid factor (RF) by a latex-agglutination test at 8, 18, 28, 38, and 48 days postinoculation (DPI). Mean total serum protein concentration was significantly elevated by 8 DPI and rose to much higher concentrations on each subsequent day of examination. The mean albumin concentration was significantly decreased by 8 DPI, and continued to decline to very low levels at 18 and 28 DPI, after which it began to rise and by 48 DPI did not significantly differ from the controls. The mean alpha-globulin concentrations were significantly elevated on all days of examination. The mean beta- and gamma-globulin concentrations were significantly elevated by 8 DPI and reached maximum levels at 18 DPI but remained elevated throughout the test. The percentage of chickens having RF titers increased on each successive examination day, but only 56% of the chickens had titers at 48 DPI.", "contents": "Progressive changes in serum proteins and the rheumatoid factor of chickens infected with Mycoplasma synoviae. Sera from controls and chickens infected with Mycoplasma synoviae were examined for serum protein content by cellulose-acetate electrophoresis, and for rheumatoid factor (RF) by a latex-agglutination test at 8, 18, 28, 38, and 48 days postinoculation (DPI). Mean total serum protein concentration was significantly elevated by 8 DPI and rose to much higher concentrations on each subsequent day of examination. The mean albumin concentration was significantly decreased by 8 DPI, and continued to decline to very low levels at 18 and 28 DPI, after which it began to rise and by 48 DPI did not significantly differ from the controls. The mean alpha-globulin concentrations were significantly elevated on all days of examination. The mean beta- and gamma-globulin concentrations were significantly elevated by 8 DPI and reached maximum levels at 18 DPI but remained elevated throughout the test. The percentage of chickens having RF titers increased on each successive examination day, but only 56% of the chickens had titers at 48 DPI."} {"id": "PMID:1259653", "title": "Antibody response and resistance of turkeys to Newcastle disease vaccine strain LaSota.", "content": "Studies were undertaken to determine the influence of repeated revaccination on the immune response in immuno-competent turkeys as measured by humoral antibody and resistance to challenge. Protection was better in turkeys given the LaSota spray vaccine at 4 weeks and 30 days later than in turkeys given one vaccination by spray or intramuscular route or exposed 4 times at 10-day intervals by the aerosol route. The anamnestic response, as measured by the HI tests to revaccination with the same immunogen, was not evident by the 3rd day postrevaccination but was observed on the 7th day. The interval between primary and secondary vaccination was found to be important to a true and optimal anamnestic response. Response was greater, however, in vaccinated turkeys exposed to VVND, a more virulent virus antigenically different from the vaccine strain. Exposure to LaSota vaccine by the intramuscular route gave a poorer HI response than LaSota given by aerosol.", "contents": "Antibody response and resistance of turkeys to Newcastle disease vaccine strain LaSota. Studies were undertaken to determine the influence of repeated revaccination on the immune response in immuno-competent turkeys as measured by humoral antibody and resistance to challenge. Protection was better in turkeys given the LaSota spray vaccine at 4 weeks and 30 days later than in turkeys given one vaccination by spray or intramuscular route or exposed 4 times at 10-day intervals by the aerosol route. The anamnestic response, as measured by the HI tests to revaccination with the same immunogen, was not evident by the 3rd day postrevaccination but was observed on the 7th day. The interval between primary and secondary vaccination was found to be important to a true and optimal anamnestic response. Response was greater, however, in vaccinated turkeys exposed to VVND, a more virulent virus antigenically different from the vaccine strain. Exposure to LaSota vaccine by the intramuscular route gave a poorer HI response than LaSota given by aerosol."} {"id": "PMID:1259666", "title": "Determination of regional pulmonary mechanics using a scintillation camera.", "content": "Electrical circuit R-C analogue models that reflect the difference in disease state between normal and diseased subjects, and normal and diseased regions of a diseased lung, were used to evaluate distal and proximal resistances and compliances for lung regions. Experimental values of regional flows and volumes for normal and diseased human lungs were obtained from a noninvasic scintillation camera technique in which the subject breathed Xe133-seeded air. Values of resistance and compliance were obtained with the additional use of an esophageal balloon. Total volumes and flows were measured through spirometry. Regional volumes were determined and regional flows were found through numerical differentiation. In analytical modeling, values of resistances and compliances were chosen so that the computed flow and volume curves corresponded to the actual flow and volume curves. Differences in resistance were an order of magnitude higher for the diseased subjects while compliances were generally several times lower than those for the normal subjects. However, the absolute values do not correlate well with those values generally found in the literature because compliance is usually measured statically and resistance measured during tidal breathing or panting. Since the forced vital capacity maneuver used here is extremely dynamic, there is significant airway collapse which results in functionally higher resistances and lower compliances. This maneuver tends to accentuate the differences between normal and diseased subjects and a subject's normal and diseased lung regions.", "contents": "Determination of regional pulmonary mechanics using a scintillation camera. Electrical circuit R-C analogue models that reflect the difference in disease state between normal and diseased subjects, and normal and diseased regions of a diseased lung, were used to evaluate distal and proximal resistances and compliances for lung regions. Experimental values of regional flows and volumes for normal and diseased human lungs were obtained from a noninvasic scintillation camera technique in which the subject breathed Xe133-seeded air. Values of resistance and compliance were obtained with the additional use of an esophageal balloon. Total volumes and flows were measured through spirometry. Regional volumes were determined and regional flows were found through numerical differentiation. In analytical modeling, values of resistances and compliances were chosen so that the computed flow and volume curves corresponded to the actual flow and volume curves. Differences in resistance were an order of magnitude higher for the diseased subjects while compliances were generally several times lower than those for the normal subjects. However, the absolute values do not correlate well with those values generally found in the literature because compliance is usually measured statically and resistance measured during tidal breathing or panting. Since the forced vital capacity maneuver used here is extremely dynamic, there is significant airway collapse which results in functionally higher resistances and lower compliances. This maneuver tends to accentuate the differences between normal and diseased subjects and a subject's normal and diseased lung regions."} {"id": "PMID:1259660", "title": "Recovery of 61 Salmonella serotypes from artificially contaminated turkey skin.", "content": "Selenite brilliant-green sulfa enrichment broth containing Tween 80 was streaked to brilliant-green sulfa plates for use in comparing recoverability of 61 different salmonella serotypes from turkey tails artifically contaminated with very low levels of each serotype. Recoverability was 100% with 43 of the serotypes, 80% with eight, 60% with four, and 40% or less with six.", "contents": "Recovery of 61 Salmonella serotypes from artificially contaminated turkey skin. Selenite brilliant-green sulfa enrichment broth containing Tween 80 was streaked to brilliant-green sulfa plates for use in comparing recoverability of 61 different salmonella serotypes from turkey tails artifically contaminated with very low levels of each serotype. Recoverability was 100% with 43 of the serotypes, 80% with eight, 60% with four, and 40% or less with six."} {"id": "PMID:1259667", "title": "Ethnic variations in psychological performance under altitude stress.", "content": "Sea-level performance of 120 subjects equally drawn from Gorkha, Madrasi, and Rajput groups was compared with that at an altitude of 4,000 m after 10 months' stay. Alterations in concentration, eye-hand coordination, anxiety, depression, and social interaction were recorded to ascertain ethnic differences in withstanding the altitude stress. Results showed a uniform fall in the scores for eye-hand coordination and social interaction at altitude for the three ethnic groups. However, the effects on concentration, anxiety, and depression were differential for these groups indicating a better toleration of altitude stress by Gorkhas. Climatic similarity between the region of natural habitat of Gorkhas and altitude environment has been suggested to be responsible for their better performance over the other two groups.", "contents": "Ethnic variations in psychological performance under altitude stress. Sea-level performance of 120 subjects equally drawn from Gorkha, Madrasi, and Rajput groups was compared with that at an altitude of 4,000 m after 10 months' stay. Alterations in concentration, eye-hand coordination, anxiety, depression, and social interaction were recorded to ascertain ethnic differences in withstanding the altitude stress. Results showed a uniform fall in the scores for eye-hand coordination and social interaction at altitude for the three ethnic groups. However, the effects on concentration, anxiety, and depression were differential for these groups indicating a better toleration of altitude stress by Gorkhas. Climatic similarity between the region of natural habitat of Gorkhas and altitude environment has been suggested to be responsible for their better performance over the other two groups."} {"id": "PMID:1259661", "title": "Focal hepatic necrosis in turkeys with hemorrhagic enteritis.", "content": "Disseminated acute focal hepatic coagulation necrosis was present in 9 turkeys submitted from 5 outbreaks of hemorrhagic enteritis. The lesion was unaccompanied by inflammatory cell infiltrate, biliary hyperplasia, or pancreatic necrosis, all of which tentatively distinguish this lesion from that of turkey viral hepatitis. No inclusion bodies were found.", "contents": "Focal hepatic necrosis in turkeys with hemorrhagic enteritis. Disseminated acute focal hepatic coagulation necrosis was present in 9 turkeys submitted from 5 outbreaks of hemorrhagic enteritis. The lesion was unaccompanied by inflammatory cell infiltrate, biliary hyperplasia, or pancreatic necrosis, all of which tentatively distinguish this lesion from that of turkey viral hepatitis. No inclusion bodies were found."} {"id": "PMID:1259668", "title": "Trying to explain an effect of \"per se\" hydrostatic pressure on heart rate in fish.", "content": "Specific effects of \"per se\" hydrostatic pressure on mean heart rate have been studied on eels (Anguilla anguilla L.), both untreated and treated with atropine and propranolol, and on isolated eel's heart. Because temperature brings, by itself, heart rate modifications in fish, a quantitative study was performed in order to take away the increment of heart rate due to the water warming, which cannot entirely be suppressed during compression. The specific effects of \"per se\" pressure have been identified as a bradycardia above 24.5 degrees C and as a tachycardia below this temperature. The use of atropine and propranol, which abolish extrinsic heart control, shows that pressure acts both through extrinsic mechanisms of heart control and through a direct action on autonomic cardiac cells. This effect of \"per se\" pressure on cardiac cells is interpreted according to chemical kinetics laws. The hypothesis that pressure acts at the molecular level, possibly by the means of reversible structure modifications of some molecules, is suggested.", "contents": "Trying to explain an effect of \"per se\" hydrostatic pressure on heart rate in fish. Specific effects of \"per se\" hydrostatic pressure on mean heart rate have been studied on eels (Anguilla anguilla L.), both untreated and treated with atropine and propranolol, and on isolated eel's heart. Because temperature brings, by itself, heart rate modifications in fish, a quantitative study was performed in order to take away the increment of heart rate due to the water warming, which cannot entirely be suppressed during compression. The specific effects of \"per se\" pressure have been identified as a bradycardia above 24.5 degrees C and as a tachycardia below this temperature. The use of atropine and propranol, which abolish extrinsic heart control, shows that pressure acts both through extrinsic mechanisms of heart control and through a direct action on autonomic cardiac cells. This effect of \"per se\" pressure on cardiac cells is interpreted according to chemical kinetics laws. The hypothesis that pressure acts at the molecular level, possibly by the means of reversible structure modifications of some molecules, is suggested."} {"id": "PMID:1259669", "title": "Effects of increased pressures of oxygen and air on short-term memory in mice.", "content": "The purpose of this study was to determine the effects of increased oxygen tensions on short-term memory in mice following one-trial, passive-avoidance learning. Neither increased oxygen tensions per se nor 6 ATA air had any measurable deleterious effects on retention of the learned task. Interference with memory of the learned task occurred only when the animals were subjected to oxygen-induced convulsions. Oxygen-induced convulsions did not result in permanent brain damage such that the animals were incapable of learning. Oxygen-induced convulsions following a 2-h interval after learning did not result in a retrograde amnesia. It appears that oxygen-induced convulsions interferes with the consolidation process of memory.", "contents": "Effects of increased pressures of oxygen and air on short-term memory in mice. The purpose of this study was to determine the effects of increased oxygen tensions on short-term memory in mice following one-trial, passive-avoidance learning. Neither increased oxygen tensions per se nor 6 ATA air had any measurable deleterious effects on retention of the learned task. Interference with memory of the learned task occurred only when the animals were subjected to oxygen-induced convulsions. Oxygen-induced convulsions did not result in permanent brain damage such that the animals were incapable of learning. Oxygen-induced convulsions following a 2-h interval after learning did not result in a retrograde amnesia. It appears that oxygen-induced convulsions interferes with the consolidation process of memory."} {"id": "PMID:1259670", "title": "Changes in pulmonary volumes with relocation to 1,600 m following acute translocation to 4,300 m.", "content": "In studies of 12 volunteer subjects, VC and ERV significantly decreased during a 3-d sojourn at 4,300 m while VE, VT, TLC, FRC and RV were elevated. Acid-base parameters showed typical changes associated with translocation to high altitude. Thus, PaO2, PaCO2 and SaO2 were immediately reduced upon translocation to 4,300 m, while the compensatory reduction in arterial HCO3- concentration was delayed temporarily by 24 h; pH, however, remained essentially unchanged throughout the sojourn. Upon relocation to 1,600 m, there was a gradual return to VC, ERV, TLC and RV to prealtitude values. FRC, on the other hand, remained elevated as did VE and VT through the third day of relocation to 1,600 m. PaCO2 and arterial HCO3- concentration showed a slight delay in returning to prealtitude values upon relocation, while the remainder of the acid-base measurements returned to prealtitude values within 24 h. The conclusion drawn from these results indicates a physiological adjustment period as long as 3 d may be required for individuals returning from a 72-h sojourn to high altitude (4,300 m).", "contents": "Changes in pulmonary volumes with relocation to 1,600 m following acute translocation to 4,300 m. In studies of 12 volunteer subjects, VC and ERV significantly decreased during a 3-d sojourn at 4,300 m while VE, VT, TLC, FRC and RV were elevated. Acid-base parameters showed typical changes associated with translocation to high altitude. Thus, PaO2, PaCO2 and SaO2 were immediately reduced upon translocation to 4,300 m, while the compensatory reduction in arterial HCO3- concentration was delayed temporarily by 24 h; pH, however, remained essentially unchanged throughout the sojourn. Upon relocation to 1,600 m, there was a gradual return to VC, ERV, TLC and RV to prealtitude values. FRC, on the other hand, remained elevated as did VE and VT through the third day of relocation to 1,600 m. PaCO2 and arterial HCO3- concentration showed a slight delay in returning to prealtitude values upon relocation, while the remainder of the acid-base measurements returned to prealtitude values within 24 h. The conclusion drawn from these results indicates a physiological adjustment period as long as 3 d may be required for individuals returning from a 72-h sojourn to high altitude (4,300 m)."} {"id": "PMID:1259664", "title": "Brain lesions in mallard ducklings from parents fed methylmercury.", "content": "Methylmercury dicyandiamide was fed to mallard ducks at 3 ppm mercury. Mercury accumulated in the eggs to an average of 7.18 and 5.46 ppm on a wet-weight basis in 2 successive years. Mercury in the eggs is believed to have caused brain lesions in the hatched ducklings. Lesions included demyelination, neuron shrink-age, necrosis, and hemorrhage in the meninges overlying the cerebellum. Brains of dead ducklings contained an average of 6.17 and 5.19 ppm mercury on a wet-weight basis in 2 successive years.", "contents": "Brain lesions in mallard ducklings from parents fed methylmercury. Methylmercury dicyandiamide was fed to mallard ducks at 3 ppm mercury. Mercury accumulated in the eggs to an average of 7.18 and 5.46 ppm on a wet-weight basis in 2 successive years. Mercury in the eggs is believed to have caused brain lesions in the hatched ducklings. Lesions included demyelination, neuron shrink-age, necrosis, and hemorrhage in the meninges overlying the cerebellum. Brains of dead ducklings contained an average of 6.17 and 5.19 ppm mercury on a wet-weight basis in 2 successive years."} {"id": "PMID:1259663", "title": "Effects of IgY antibody on the development of Marek's disease.", "content": "The effects of passive immunization with immunoglobulin Y (IgY) on the pathogenesis of Marek's disease (MD) were examined in an experimental line of White Leghorn chickens highly susceptible to MD. Purified IgY with anti-MDV antibody activity, when injected into chicks, delayed the development of MDV viremia and lesions until 9 days postinoculation (PI) with Marek's disease virus (MDV). The blastogenic response of spleen cells to concanavallin-A was depressed at 6 days PI in the birds without passive immunization, whereas it was not totally depressed until 17 days in birds passively immunized with IgY anti-MDV antibody.", "contents": "Effects of IgY antibody on the development of Marek's disease. The effects of passive immunization with immunoglobulin Y (IgY) on the pathogenesis of Marek's disease (MD) were examined in an experimental line of White Leghorn chickens highly susceptible to MD. Purified IgY with anti-MDV antibody activity, when injected into chicks, delayed the development of MDV viremia and lesions until 9 days postinoculation (PI) with Marek's disease virus (MDV). The blastogenic response of spleen cells to concanavallin-A was depressed at 6 days PI in the birds without passive immunization, whereas it was not totally depressed until 17 days in birds passively immunized with IgY anti-MDV antibody."} {"id": "PMID:1259671", "title": "Head and neck cooling by air, water, or air plus water in hyperthermia.", "content": "The effects of air, water, and air plus water head cooling on thermoregulatory responses and human operator performance were studied in nonacclimatized, heat-exposed men. Forty chamber exposures (46 degrees C, 30 mm Hg water vapor pressure) were conducted under noncooled and the aforementioned subconditions of head cooling. Five subjects, exposed for 80 min, were monitored for mean skin and rectal temperatures, heart rate, sweat loss, and compensatory tracking performance. A modified Air Force helmet shell provided facial air ventilation (24 degrees C) at 8 cfm. Eight interconnected neoprene modules fastened beneath a helmet linear provided water cooling (20 degrees C at 0.9 l/min). Tracking performances was unchanged across conditions. Elevation of rectal temperature and heart rate, sweat loss, and Physiological Index of Strain were significantly reduced by each condition of head cooling. Air is as effective as water as a cooling agent. Air ventilation acts synergistically with water cooling in reducing physiological strain. Relative merits of each approach to head cooling, in an operational context, are discussed.", "contents": "Head and neck cooling by air, water, or air plus water in hyperthermia. The effects of air, water, and air plus water head cooling on thermoregulatory responses and human operator performance were studied in nonacclimatized, heat-exposed men. Forty chamber exposures (46 degrees C, 30 mm Hg water vapor pressure) were conducted under noncooled and the aforementioned subconditions of head cooling. Five subjects, exposed for 80 min, were monitored for mean skin and rectal temperatures, heart rate, sweat loss, and compensatory tracking performance. A modified Air Force helmet shell provided facial air ventilation (24 degrees C) at 8 cfm. Eight interconnected neoprene modules fastened beneath a helmet linear provided water cooling (20 degrees C at 0.9 l/min). Tracking performances was unchanged across conditions. Elevation of rectal temperature and heart rate, sweat loss, and Physiological Index of Strain were significantly reduced by each condition of head cooling. Air is as effective as water as a cooling agent. Air ventilation acts synergistically with water cooling in reducing physiological strain. Relative merits of each approach to head cooling, in an operational context, are discussed."} {"id": "PMID:1259662", "title": "Clinical, cultural, and serologic observations of avian mycoplasmosis in two chicken breeder flocks.", "content": "Two chicken breeding flocks from different breeding lines were studied serologically and culturally for Mycoplasma gallisepticum (MG) throughout their growing and laying period. Infection was proven by successful isolation of MG from both breeders and progeny originating from these two flocks. Observations of these flocks which were serologically and culturally negative for Mycoplasma synoviae (MS) further disclosed that: 1) negative plate tests of large numbers of day-old progeny may sometimes be found in flocks known to be infected with MG; 2) it may be very difficult to isolate MG consistently from some infected flocks; 3) overgrowth of M. gallinarum may interfere with successful cultivation of MG; 4) a persistent breeder flock reactor rate of greater than 10-20% but less than 80-100% for a 4-to-12-week period is a strong indication of MG infection despite weak or negative MG hemagglutination-inhibition (HI) test results; and 5) antibodies for all strains of MG may not react equally to the standard USDA MG-HI antigen.", "contents": "Clinical, cultural, and serologic observations of avian mycoplasmosis in two chicken breeder flocks. Two chicken breeding flocks from different breeding lines were studied serologically and culturally for Mycoplasma gallisepticum (MG) throughout their growing and laying period. Infection was proven by successful isolation of MG from both breeders and progeny originating from these two flocks. Observations of these flocks which were serologically and culturally negative for Mycoplasma synoviae (MS) further disclosed that: 1) negative plate tests of large numbers of day-old progeny may sometimes be found in flocks known to be infected with MG; 2) it may be very difficult to isolate MG consistently from some infected flocks; 3) overgrowth of M. gallinarum may interfere with successful cultivation of MG; 4) a persistent breeder flock reactor rate of greater than 10-20% but less than 80-100% for a 4-to-12-week period is a strong indication of MG infection despite weak or negative MG hemagglutination-inhibition (HI) test results; and 5) antibodies for all strains of MG may not react equally to the standard USDA MG-HI antigen."} {"id": "PMID:1259672", "title": "Vestibular habituation in flightcrew.", "content": "Vestibular habituation is a general reaction to any repetitive sensory stimulation. It can be characterized by four main features: acquisition, retention, loss or dishabituation, and transfer. This study concerns three groups of subjects: The first group consists of a) 27 pilots at present serving in the French Air Force, b) 12 pilots at present serving in the major civil airlines, c) 8 navigators, radio-navigators, and crew mechanics, some of whom are flying club pilots, and d) 3 professional pilots trained in flying clubs. All of these subjects had more than 2000 h flying time. They were from 27 to 50 years old. The second group consists of airline stewards. The third group consists of trainee pilots still in flying school. All of these subjects were examined for their suitability, in particular undergoing a damped swing test. The first oscillation was in an anticlockwise direction and the damping extended over 20 periods. The following parametre was measured: the ratio of total left nystagmus frequency to total right nystagmus frequency. In \"normal\" control subjects the ratio is greater than 1. The results were: The first group: In 41 out of 50 subjects, the ratio of left tremors frequency to right tremors frequency was less than or approximately equal to 1. In the second group: The results showed no significant differences in comparison with a control group of subjects. In the third group: Zero flying time--the results were identical with those of control subjects; 40 h flying time--the ratio approached 1; 100 h flying time--the ratio was less than 1. Vestibular habituation, that is inversion of the preponderance of the total number of left tremors over the total number of right tremors, was observed in the technical flightcrew. The appearance of this inversion during the pilots' training was studied and its retention tested. This test for showing vestibular habituation may be of use for monitoring the function of equilibrium and the development of habituation during flight training. In this report, we shall first review the definition and characteristics of vestibular habituation, and the main body of recent work on this phenomenon in flightcrew. Our own findings will be then presented.", "contents": "Vestibular habituation in flightcrew. Vestibular habituation is a general reaction to any repetitive sensory stimulation. It can be characterized by four main features: acquisition, retention, loss or dishabituation, and transfer. This study concerns three groups of subjects: The first group consists of a) 27 pilots at present serving in the French Air Force, b) 12 pilots at present serving in the major civil airlines, c) 8 navigators, radio-navigators, and crew mechanics, some of whom are flying club pilots, and d) 3 professional pilots trained in flying clubs. All of these subjects had more than 2000 h flying time. They were from 27 to 50 years old. The second group consists of airline stewards. The third group consists of trainee pilots still in flying school. All of these subjects were examined for their suitability, in particular undergoing a damped swing test. The first oscillation was in an anticlockwise direction and the damping extended over 20 periods. The following parametre was measured: the ratio of total left nystagmus frequency to total right nystagmus frequency. In \"normal\" control subjects the ratio is greater than 1. The results were: The first group: In 41 out of 50 subjects, the ratio of left tremors frequency to right tremors frequency was less than or approximately equal to 1. In the second group: The results showed no significant differences in comparison with a control group of subjects. In the third group: Zero flying time--the results were identical with those of control subjects; 40 h flying time--the ratio approached 1; 100 h flying time--the ratio was less than 1. Vestibular habituation, that is inversion of the preponderance of the total number of left tremors over the total number of right tremors, was observed in the technical flightcrew. The appearance of this inversion during the pilots' training was studied and its retention tested. This test for showing vestibular habituation may be of use for monitoring the function of equilibrium and the development of habituation during flight training. In this report, we shall first review the definition and characteristics of vestibular habituation, and the main body of recent work on this phenomenon in flightcrew. Our own findings will be then presented."} {"id": "PMID:1259673", "title": "Prolonged visual loss and bradycardia following deceleration from +6 gz acceleration: a case report.", "content": "Visual blackout during high GZ acceleration is not an unusual phenomenon. Bradycardia is often seen following similar acceleration exposure. An instance of prolonged visual loss associated with bradycardia following a +6 GZ acceleration is described. Possible mechanisms are proposed, and significance in the study of high acceleration is discussed.", "contents": "Prolonged visual loss and bradycardia following deceleration from +6 gz acceleration: a case report. Visual blackout during high GZ acceleration is not an unusual phenomenon. Bradycardia is often seen following similar acceleration exposure. An instance of prolonged visual loss associated with bradycardia following a +6 GZ acceleration is described. Possible mechanisms are proposed, and significance in the study of high acceleration is discussed."} {"id": "PMID:1259665", "title": "Cell-mediated and humoral immune response of chickens to Mycoplasma synoviae.", "content": "The leukocyte migration-inhibition test was employed to demonstrate the presence of cell-mediated immunity and to ascertain its relation to immunoglobulin production in Mycoplasma synoviae infection in chickens. With peripheral leukocytes and a preparation of M. synoviae used as antigen, good discrimination was obtained between naturally or experimentally infected birds and uninfected control birds. Only the infected groups showed significant inhibition. Positive migration inhibition values developed in the second week of infection, often before the appearance of hemagglutination-inhibition titers, and continued to accompany the production of immunoglobulins with some degree of correlation for at least 6 or 12 months.", "contents": "Cell-mediated and humoral immune response of chickens to Mycoplasma synoviae. The leukocyte migration-inhibition test was employed to demonstrate the presence of cell-mediated immunity and to ascertain its relation to immunoglobulin production in Mycoplasma synoviae infection in chickens. With peripheral leukocytes and a preparation of M. synoviae used as antigen, good discrimination was obtained between naturally or experimentally infected birds and uninfected control birds. Only the infected groups showed significant inhibition. Positive migration inhibition values developed in the second week of infection, often before the appearance of hemagglutination-inhibition titers, and continued to accompany the production of immunoglobulins with some degree of correlation for at least 6 or 12 months."} {"id": "PMID:1259681", "title": "[Injection methods for the demonstration of the coronary arterial vasculature (author's transl)].", "content": "Four different methods for the demonstration of the coronary arterial vasculature are examined. Among the techniques studied corrosion casts (epoxid- and acrylic resin) permit the best qualitative and quantitative evaluation of superficial and deep arteries and arterioles. Down to the smallest infusible vessels of 15-25 mum there is practically no shrinkage. X-ray arteriography with an aqueous solution of barium sulphate is less suitable because X-rays allow no satisfactory stereoscopic view. The demonstration of arterioles and collaterals is limited to vessels larger than 50 mum because of the low resolution of the X-ray tube. Silicone rubber does not only fill the arteries, but also the capillary bed and the venous system. Therefore deeper parts of the vasculature can only be studied after slicing the heart. The substantial shrinkage of the material makes quantitative measurements difficult.", "contents": "[Injection methods for the demonstration of the coronary arterial vasculature (author's transl)]. Four different methods for the demonstration of the coronary arterial vasculature are examined. Among the techniques studied corrosion casts (epoxid- and acrylic resin) permit the best qualitative and quantitative evaluation of superficial and deep arteries and arterioles. Down to the smallest infusible vessels of 15-25 mum there is practically no shrinkage. X-ray arteriography with an aqueous solution of barium sulphate is less suitable because X-rays allow no satisfactory stereoscopic view. The demonstration of arterioles and collaterals is limited to vessels larger than 50 mum because of the low resolution of the X-ray tube. Silicone rubber does not only fill the arteries, but also the capillary bed and the venous system. Therefore deeper parts of the vasculature can only be studied after slicing the heart. The substantial shrinkage of the material makes quantitative measurements difficult."} {"id": "PMID:1259680", "title": "The effect of isolation on myocardial properties.", "content": "Denervation deprives the heart of its normal adrenergic and cholinergic control via the sympathetic and parasympathetic pathways. In a heart which is blood supplied by a donor animal of the same species, normal contractility is maintained, probably by blood borne catecholamines or possibly by unknown inotropic agents of the donor. A heart receiving blood oxygenated by isolated lungs is in a state of failure. Substitution of blood by a cell and protein free solution diminishes oxygen availability in cardiac muscle, both in the perfused and bathed preparation. In the unphysiological environment, myocardial cells lose K+ and gain Na+. Under best possible conditions of oxygen supply but in a later stage of perfusion, contractility during rhythmical stimulation is depressed more at lower than at higher rates. Frequency potentiation and the inotropic effectiveness of noradrenaline is more pronounced in vitro than in situ. In excised papillary muscles and ventricular and atrial strips, the disarrangement and a more or less severe lesion of individual fibres accelerates the decay in mechanical performance. The role of endogenous catecholamines for the maintenance of normal contractility in situ and in vitro is still a matter of discussion.", "contents": "The effect of isolation on myocardial properties. Denervation deprives the heart of its normal adrenergic and cholinergic control via the sympathetic and parasympathetic pathways. In a heart which is blood supplied by a donor animal of the same species, normal contractility is maintained, probably by blood borne catecholamines or possibly by unknown inotropic agents of the donor. A heart receiving blood oxygenated by isolated lungs is in a state of failure. Substitution of blood by a cell and protein free solution diminishes oxygen availability in cardiac muscle, both in the perfused and bathed preparation. In the unphysiological environment, myocardial cells lose K+ and gain Na+. Under best possible conditions of oxygen supply but in a later stage of perfusion, contractility during rhythmical stimulation is depressed more at lower than at higher rates. Frequency potentiation and the inotropic effectiveness of noradrenaline is more pronounced in vitro than in situ. In excised papillary muscles and ventricular and atrial strips, the disarrangement and a more or less severe lesion of individual fibres accelerates the decay in mechanical performance. The role of endogenous catecholamines for the maintenance of normal contractility in situ and in vitro is still a matter of discussion."} {"id": "PMID:1259682", "title": "The slow membrane channel as the predominant mediator of the excitation process of the sinoatrial pacemaker cell.", "content": "The slow upstroke velocity of the action potential of primary pacemaker cells of the sinoatrial node suggests the slow membrane channel to be involved in the excitation process of these cells. In order to prove this the effect of promotors and inhibitors of the slow membrane channel upon the excitation process of the isolated sinoatrial node of rabbits was studied. 1. The action potentials of primary pacemaker cells had an upstroke velocity of 1.7 +/- 1.1 V/sec and an overshoot of 8.1 +/- 4.6 mV with a threshold potential of -40.1 +/- 4.5 mV. A decrease of the extracellular Ca concentration from 2 mM to 0.2 mM led to reduction of upstroke velocity and overshoot whereas an increase from 2 mM to 4 mM augmented both parameters. But the inward current is not only carried by Ca ions but by Na ions as well, since Na withdrawal diminished upstroke velocity and overshoot. 2. The promotors of the slow inward current, isoproterenol and caffeine, produced a significant increase of upstroke velocity and overshoot. On the other hand, verapamil (1 mg/1) and D 600 (0.4 MG/1) completely blocked the excitation process within 20-25 min. The same effect could be produced by the bivalent cations Ni (1 mM), Co (1 mM), and Mn (1 mM). These organic and inorganic inhibitors exerted their blocking effect without significant changes of the maximal diastolic potential and the threshold potential. 3. In the continued presence of Ni, Co and Mn ions their inhibitory effect could be neutralized nearly completely by isoproterenol (2.5 mg/1). But excess Ca (6 mM) increased the upstroke velocity only to a small degree. In contrast to the findings in the ventricular myocardium the blocking effect of verapamil and D 600 could be overcome neither by isoproterenol nor by excess Ca. The excitation process in the sinotrial node is mediated solely by the slow membrane channel. It allows the influx of both Ca and Na ions which act as charge carrier of the slow inward current. The fact, that the inhibitory effect of verapamil and D 600 cannot be neutralized by catecholamines or excess Ca seems to indicate that some properties of the slow membrane channel are not exactly identical in sinotrial pacemaker cells and in the ventricular myocardium.", "contents": "The slow membrane channel as the predominant mediator of the excitation process of the sinoatrial pacemaker cell. The slow upstroke velocity of the action potential of primary pacemaker cells of the sinoatrial node suggests the slow membrane channel to be involved in the excitation process of these cells. In order to prove this the effect of promotors and inhibitors of the slow membrane channel upon the excitation process of the isolated sinoatrial node of rabbits was studied. 1. The action potentials of primary pacemaker cells had an upstroke velocity of 1.7 +/- 1.1 V/sec and an overshoot of 8.1 +/- 4.6 mV with a threshold potential of -40.1 +/- 4.5 mV. A decrease of the extracellular Ca concentration from 2 mM to 0.2 mM led to reduction of upstroke velocity and overshoot whereas an increase from 2 mM to 4 mM augmented both parameters. But the inward current is not only carried by Ca ions but by Na ions as well, since Na withdrawal diminished upstroke velocity and overshoot. 2. The promotors of the slow inward current, isoproterenol and caffeine, produced a significant increase of upstroke velocity and overshoot. On the other hand, verapamil (1 mg/1) and D 600 (0.4 MG/1) completely blocked the excitation process within 20-25 min. The same effect could be produced by the bivalent cations Ni (1 mM), Co (1 mM), and Mn (1 mM). These organic and inorganic inhibitors exerted their blocking effect without significant changes of the maximal diastolic potential and the threshold potential. 3. In the continued presence of Ni, Co and Mn ions their inhibitory effect could be neutralized nearly completely by isoproterenol (2.5 mg/1). But excess Ca (6 mM) increased the upstroke velocity only to a small degree. In contrast to the findings in the ventricular myocardium the blocking effect of verapamil and D 600 could be overcome neither by isoproterenol nor by excess Ca. The excitation process in the sinotrial node is mediated solely by the slow membrane channel. It allows the influx of both Ca and Na ions which act as charge carrier of the slow inward current. The fact, that the inhibitory effect of verapamil and D 600 cannot be neutralized by catecholamines or excess Ca seems to indicate that some properties of the slow membrane channel are not exactly identical in sinotrial pacemaker cells and in the ventricular myocardium."} {"id": "PMID:1259683", "title": "Acetylation of nuclear proteins in the isolated perfused rat heart.", "content": "Female rat hearts were maintained by retrograde perfusion under a hydrostatic pressure of 75 cm H2O. The perfused heart had a coronary flow of 8-9 ml/min and a heart rate of 220-240 beats/min. Recirculation of [3H]acetate (2 muCi/ml perfusate) for 20 min was sufficient to label nuclear proteins. Total nuclear proteins were separated into three major classes: (1) 0.14 M NaCl soluble nucleoplasmic proteins, (2) nucleohistones and (3) nonhistone residual proteins. Approximately 88-90% of the (3H)acetate incorporated was found in the nucleohistone fraction. Polyacrylamide-urea gel electrophoresis of the histones indicated that fraction f1 was not acetylated while f3 and f2al were highly acetylated, containing 75% of the total histone radioactivity. Fraction f2b + f2a2 was moderately acetylated contributing 20-25% of the radioactivity. Nucleohistones isolated from myocardial cells showed the same percentage distribution of (3H)acetate in the histone fractions as the whole heart. Acid hydrolysis followed by steam distillation released more than 95% of the acetyl groups from the two major nucleoproteins. These data suggest that the isolated perfused heart may provide a model system to study covalent modification of nucleoproteins under controlled physiological and biochemical conditions.", "contents": "Acetylation of nuclear proteins in the isolated perfused rat heart. Female rat hearts were maintained by retrograde perfusion under a hydrostatic pressure of 75 cm H2O. The perfused heart had a coronary flow of 8-9 ml/min and a heart rate of 220-240 beats/min. Recirculation of [3H]acetate (2 muCi/ml perfusate) for 20 min was sufficient to label nuclear proteins. Total nuclear proteins were separated into three major classes: (1) 0.14 M NaCl soluble nucleoplasmic proteins, (2) nucleohistones and (3) nonhistone residual proteins. Approximately 88-90% of the (3H)acetate incorporated was found in the nucleohistone fraction. Polyacrylamide-urea gel electrophoresis of the histones indicated that fraction f1 was not acetylated while f3 and f2al were highly acetylated, containing 75% of the total histone radioactivity. Fraction f2b + f2a2 was moderately acetylated contributing 20-25% of the radioactivity. Nucleohistones isolated from myocardial cells showed the same percentage distribution of (3H)acetate in the histone fractions as the whole heart. Acid hydrolysis followed by steam distillation released more than 95% of the acetyl groups from the two major nucleoproteins. These data suggest that the isolated perfused heart may provide a model system to study covalent modification of nucleoproteins under controlled physiological and biochemical conditions."} {"id": "PMID:1259684", "title": "Transmural differences in myocardial blood flow and in coronary dilatory capacity in hemodiluted conscious dogs.", "content": "In 16 conscious resting dogs regional myocardial blood flow and the local coronary dilatory capacity were studied with the particle distribution technique during isovolemic hemodilution (hct = 13%). Postischemic peak coronary hyperemia following release of temporary circumflex coronary artery occlusion was used for quantification of regional coronary dilatory capacity. In hemodilution (arterial blood oxygen content less than one third of normal) left ventricular blood flow (LVBF) was 460 +/- 36 ml/100 g - min, subendocardial/subepicardial flow amounted to 1.3 +/- 0.1. During postischemic peak hyperemia LVBF increased by 33% up to 606 +/- 63 ml/100 g - min. This 33% increase in LVBF was distributed mainly to the subepicardial layer, while in the subendocardial layer there was no significant flow increase. It is concluded that the increase in heart rate and systolic coronary vascular compression in addition to the lowered arterial oxygen content lead to exhaustion of the dilatory reserve in the subendocardium during hemodilution. Therefore the remaining overall dilatory capacity is without functional significance.", "contents": "Transmural differences in myocardial blood flow and in coronary dilatory capacity in hemodiluted conscious dogs. In 16 conscious resting dogs regional myocardial blood flow and the local coronary dilatory capacity were studied with the particle distribution technique during isovolemic hemodilution (hct = 13%). Postischemic peak coronary hyperemia following release of temporary circumflex coronary artery occlusion was used for quantification of regional coronary dilatory capacity. In hemodilution (arterial blood oxygen content less than one third of normal) left ventricular blood flow (LVBF) was 460 +/- 36 ml/100 g - min, subendocardial/subepicardial flow amounted to 1.3 +/- 0.1. During postischemic peak hyperemia LVBF increased by 33% up to 606 +/- 63 ml/100 g - min. This 33% increase in LVBF was distributed mainly to the subepicardial layer, while in the subendocardial layer there was no significant flow increase. It is concluded that the increase in heart rate and systolic coronary vascular compression in addition to the lowered arterial oxygen content lead to exhaustion of the dilatory reserve in the subendocardium during hemodilution. Therefore the remaining overall dilatory capacity is without functional significance."} {"id": "PMID:1259685", "title": "Hemorrhagic shock with fixed hypotension and with spontaneous recovery of blood pressure. A comparison of two shock models.", "content": "In 26 dogs anesthetized with a barbiturate peripheral blood flow, O2 consumption and acid-base balance have been studied in two kinds of hemorrhagic shock: 1. Hemorrhagic shock with fixed hypotension (hypotensive shock, n = 12) 2. Hemorrhagic shock with spontaneously recovering arterial blood pressure (normotensive shock, n = 14). In both groups the same amount of blood is withdrawn and stored in a reservoir (31-32 ml/kg) to reduce arterial pressure to 40 mm Hg. In hypotensive shock there is a continuous outflow of blood into the reservoir in order to maintain an arterial pressure of 40 mm Hg. After 1 1/2 hours this shift of blood reverses itself spontaneously. In normotensive shock the arterial pressure is allowed to increase after the initial withdrawal of blood. 1 1/2 hours later it reaches a peak of 93 mm Hg after which it starts declining again. The duration of oligemia which the animals control themselves is nearly identical in both groups (4 hours). Both kinds of hemorrhagic shock have a mortality rate of 80%. The survival time is shorter (p less than 0.01) in hypotensive (3 hours) than in normotensive shock (7 1/2 hours). In both kinds of shock heart rate increases to more than 200 beats/min. However, in hypotensive shock it decreases in the late stage of hypovolemia, whereas the increase is continuous in normotensive shock. Cardiac output is significantly higher in the normotensive animals nearly throughout the entire hypovolemic phase although the initial decrease is the same in both groups (71%). Also a greater increase in total peripheral resistance occurs in these animals. The increased cardiac output and total peripheral resistance. A \"centralization\" of the circulation is also observed in this kind of shock as is made evident by the changes in the relationship between cardiac output and carotid blood flow. Hyperventilation occurs in both kinds of shock. In hypotensive shock respiratory rate decreases at the end of the oligemic phase possibly due to a smaller cerebral blood flow.", "contents": "Hemorrhagic shock with fixed hypotension and with spontaneous recovery of blood pressure. A comparison of two shock models. In 26 dogs anesthetized with a barbiturate peripheral blood flow, O2 consumption and acid-base balance have been studied in two kinds of hemorrhagic shock: 1. Hemorrhagic shock with fixed hypotension (hypotensive shock, n = 12) 2. Hemorrhagic shock with spontaneously recovering arterial blood pressure (normotensive shock, n = 14). In both groups the same amount of blood is withdrawn and stored in a reservoir (31-32 ml/kg) to reduce arterial pressure to 40 mm Hg. In hypotensive shock there is a continuous outflow of blood into the reservoir in order to maintain an arterial pressure of 40 mm Hg. After 1 1/2 hours this shift of blood reverses itself spontaneously. In normotensive shock the arterial pressure is allowed to increase after the initial withdrawal of blood. 1 1/2 hours later it reaches a peak of 93 mm Hg after which it starts declining again. The duration of oligemia which the animals control themselves is nearly identical in both groups (4 hours). Both kinds of hemorrhagic shock have a mortality rate of 80%. The survival time is shorter (p less than 0.01) in hypotensive (3 hours) than in normotensive shock (7 1/2 hours). In both kinds of shock heart rate increases to more than 200 beats/min. However, in hypotensive shock it decreases in the late stage of hypovolemia, whereas the increase is continuous in normotensive shock. Cardiac output is significantly higher in the normotensive animals nearly throughout the entire hypovolemic phase although the initial decrease is the same in both groups (71%). Also a greater increase in total peripheral resistance occurs in these animals. The increased cardiac output and total peripheral resistance. A \"centralization\" of the circulation is also observed in this kind of shock as is made evident by the changes in the relationship between cardiac output and carotid blood flow. Hyperventilation occurs in both kinds of shock. In hypotensive shock respiratory rate decreases at the end of the oligemic phase possibly due to a smaller cerebral blood flow."} {"id": "PMID:1259686", "title": "An operated case of Holt-Oram syndrome with autosomal dominant inheritance.", "content": "This report is concerned with a patient successfully operated for Holt-Oram syndrome. The disorder is inherited dominantly with complete penetrance and variable expressivity. It is pointed out that in cases of congenital heart disease familial cumulation must be borne in mind which can easily be verified by pedigree investigation. After demonstrating autosomal dominant inheritance, suitable inferences must be drawn for genetic counseling. Attention is drawn to the heart-surgical significance of the rhythm disorders so often associated with the syndrome.", "contents": "An operated case of Holt-Oram syndrome with autosomal dominant inheritance. This report is concerned with a patient successfully operated for Holt-Oram syndrome. The disorder is inherited dominantly with complete penetrance and variable expressivity. It is pointed out that in cases of congenital heart disease familial cumulation must be borne in mind which can easily be verified by pedigree investigation. After demonstrating autosomal dominant inheritance, suitable inferences must be drawn for genetic counseling. Attention is drawn to the heart-surgical significance of the rhythm disorders so often associated with the syndrome."} {"id": "PMID:1259687", "title": "Effect of high doses of nicotine in pigs. I. Changes of the electrocardiogram.", "content": "Pigs in which venous catheters were positioned for long-term use were injected i.v. with high doses of nicotine in physiol. saline. The LD50 was 2.656 mg/kg body weight. Clinical symptoms were mainly: forced respiration, muscular tremor to tetanoid spasms, cyanosis of the skin, salivation and sometimes vomiting. The degree and duration of symptoms were dose-dependent. Ecg changes in anaesthesized pigs following intravenous nicotine injections of 0.126 mg/kg and 0.378 mg/kg at 15 minutes' interval were immediately commencing disturbances of the heart rate in form of bradycardia and asystolia. After 5 sec we observed extrasystoles, tachycardia, sino-auricular block and AV-block of first and second degree as well as a number of T- and P-changes. Changes of the ecg were observed generally for 10 to 15 min, however, the T-wave remained sometimes negative or biphasic-preterminal negative for some hours.", "contents": "Effect of high doses of nicotine in pigs. I. Changes of the electrocardiogram. Pigs in which venous catheters were positioned for long-term use were injected i.v. with high doses of nicotine in physiol. saline. The LD50 was 2.656 mg/kg body weight. Clinical symptoms were mainly: forced respiration, muscular tremor to tetanoid spasms, cyanosis of the skin, salivation and sometimes vomiting. The degree and duration of symptoms were dose-dependent. Ecg changes in anaesthesized pigs following intravenous nicotine injections of 0.126 mg/kg and 0.378 mg/kg at 15 minutes' interval were immediately commencing disturbances of the heart rate in form of bradycardia and asystolia. After 5 sec we observed extrasystoles, tachycardia, sino-auricular block and AV-block of first and second degree as well as a number of T- and P-changes. Changes of the ecg were observed generally for 10 to 15 min, however, the T-wave remained sometimes negative or biphasic-preterminal negative for some hours."} {"id": "PMID:1259689", "title": "[Potassium-dependent modification of the lidocaine effect: an experimental investigation (author's transl)].", "content": "Lidocaine was supplied to 10 cats by 2 comparative infusions of 7.5 mg/kg respectively. Once the drug was dissolved in a physiological and the other time in a K-Mg-concentrated electrolyte solution. The sequence of both infusions alternated. Serum potassium remained constant during infusion of the physiological electrolyte solution, but increased by about 1 mEqu/1 under K-concentrated solution. Lidocaine caused an enhancement of ventricular fibrillation threshold to an absolutely identical degree in both groups. Increase in cardiac output and stroke volume and decrease of sinus rate was significant in both groups, but more pronounced under K-Mg concentrated solution. Mean arterial pressure, peripheral vascular resistance, PQ, QRS, and QT interval remained constant on the whole. We deduce from these results for antiarrhythmic therapy on normokalemic patients, that the addition of potassium and magnesium to lidocaine solution does not enhance its antifibrillatory effect. This statement is valid for doses up to 20 mEqu/h of magnesium and 40 mEqu/h of potassium.", "contents": "[Potassium-dependent modification of the lidocaine effect: an experimental investigation (author's transl)]. Lidocaine was supplied to 10 cats by 2 comparative infusions of 7.5 mg/kg respectively. Once the drug was dissolved in a physiological and the other time in a K-Mg-concentrated electrolyte solution. The sequence of both infusions alternated. Serum potassium remained constant during infusion of the physiological electrolyte solution, but increased by about 1 mEqu/1 under K-concentrated solution. Lidocaine caused an enhancement of ventricular fibrillation threshold to an absolutely identical degree in both groups. Increase in cardiac output and stroke volume and decrease of sinus rate was significant in both groups, but more pronounced under K-Mg concentrated solution. Mean arterial pressure, peripheral vascular resistance, PQ, QRS, and QT interval remained constant on the whole. We deduce from these results for antiarrhythmic therapy on normokalemic patients, that the addition of potassium and magnesium to lidocaine solution does not enhance its antifibrillatory effect. This statement is valid for doses up to 20 mEqu/h of magnesium and 40 mEqu/h of potassium."} {"id": "PMID:1259688", "title": "[The calcium metabolism of myocardial mitochondria and sarcoplasmic reticulum in experimental potassium deficiency (author's transl)].", "content": "Mechanical Parameters of the whole, Langendorff-perfused cat heart and of isolated right ventricular papillary muscles are depressed in chronic potassium deficiency. 45Ca binding of sarcoplasmic reticulum (SR) was found to be diminished and correlated with a reduced contractility of the perfused hearts. 45Ca uptake of sarcoplasmic reticulum isolated from potassium deficient hearts was also reduced. The mitrochondrial 45Ca binding and endogenous Ca concentration were increased and there was a positive correlation between these two parameters. The data suggest that a reduced SR Ca binding plays a role in the depression of myocardial contractility in chronic potassium deficiency. Increased mitochondrial 45Ca binding in the presence of reduced 45Ca binding and uptake of sarcoplasmic reticulum suggests the possibility that mitochondria are an additional myocardial calcium pool in chronic potassium deficiency.", "contents": "[The calcium metabolism of myocardial mitochondria and sarcoplasmic reticulum in experimental potassium deficiency (author's transl)]. Mechanical Parameters of the whole, Langendorff-perfused cat heart and of isolated right ventricular papillary muscles are depressed in chronic potassium deficiency. 45Ca binding of sarcoplasmic reticulum (SR) was found to be diminished and correlated with a reduced contractility of the perfused hearts. 45Ca uptake of sarcoplasmic reticulum isolated from potassium deficient hearts was also reduced. The mitrochondrial 45Ca binding and endogenous Ca concentration were increased and there was a positive correlation between these two parameters. The data suggest that a reduced SR Ca binding plays a role in the depression of myocardial contractility in chronic potassium deficiency. Increased mitochondrial 45Ca binding in the presence of reduced 45Ca binding and uptake of sarcoplasmic reticulum suggests the possibility that mitochondria are an additional myocardial calcium pool in chronic potassium deficiency."} {"id": "PMID:1259690", "title": "[The significance of the half axial projection in coronary angiography (author's transl)].", "content": "The proximal segments of the left coronary artery are foreshortended in the usual projections. By additional cranio-caudal (half axial) projections the X-ray beam can be directed perpendicular to these segments. In some patients lesions especially of the left main coronary artery or the proximal LAD can be seen or accurately evaluated only in the half axial projection, as demonstrated by examples. The clinical implications are discussed.", "contents": "[The significance of the half axial projection in coronary angiography (author's transl)]. The proximal segments of the left coronary artery are foreshortended in the usual projections. By additional cranio-caudal (half axial) projections the X-ray beam can be directed perpendicular to these segments. In some patients lesions especially of the left main coronary artery or the proximal LAD can be seen or accurately evaluated only in the half axial projection, as demonstrated by examples. The clinical implications are discussed."} {"id": "PMID:1259699", "title": "Polymorphism of esterase-10 in Mus musculus.", "content": "An esterase, esterase-10, in the house mouse, Mus musculus, is specific for esters of 4-methylumbelliferone and exhibits a polymorphism detectable by electrophoresis. Fifteen inbred strains and two outbred strains have been examined for this polymorphism, and two phenotypes, ES-10A and ES-10B, have been observed. Each phenotype manifests itself as a single band of enzyme activity, but under the electrophoretic conditions used the ES-10A phenotype has less anodal electrophoretic mobility than the ES-10B phenotype. In F1 hybrids (C3H/He/LacxC57BL/Gr) a third phenotype was observed, ES-10AB, consisting of three bands of enzyme activity, two of which correspond to the parental forms and the third with intermediate mobility. The triple-band pattern in the F1 hybrids indicates that esterase-10 is a dimeric enzyme protein.", "contents": "Polymorphism of esterase-10 in Mus musculus. An esterase, esterase-10, in the house mouse, Mus musculus, is specific for esters of 4-methylumbelliferone and exhibits a polymorphism detectable by electrophoresis. Fifteen inbred strains and two outbred strains have been examined for this polymorphism, and two phenotypes, ES-10A and ES-10B, have been observed. Each phenotype manifests itself as a single band of enzyme activity, but under the electrophoretic conditions used the ES-10A phenotype has less anodal electrophoretic mobility than the ES-10B phenotype. In F1 hybrids (C3H/He/LacxC57BL/Gr) a third phenotype was observed, ES-10AB, consisting of three bands of enzyme activity, two of which correspond to the parental forms and the third with intermediate mobility. The triple-band pattern in the F1 hybrids indicates that esterase-10 is a dimeric enzyme protein."} {"id": "PMID:1259700", "title": "Hemoglobin polymorphism in the encinal mouse, Peromyscus pectoralis.", "content": "Horizontal starch gel electrophoresis revealed five hemoglobin phenotypes in natural populations of the encinal mouse, Peromyscus pectoralis, from northeastern Mexico. Populations of the encinal mouse from Texas, Oklahoma, and northwestern and north central Mexico were monomorphic for multiple-band phenotypes. Analysis of the hemoglobin polymorphism indicates that two loci control this variation.", "contents": "Hemoglobin polymorphism in the encinal mouse, Peromyscus pectoralis. Horizontal starch gel electrophoresis revealed five hemoglobin phenotypes in natural populations of the encinal mouse, Peromyscus pectoralis, from northeastern Mexico. Populations of the encinal mouse from Texas, Oklahoma, and northwestern and north central Mexico were monomorphic for multiple-band phenotypes. Analysis of the hemoglobin polymorphism indicates that two loci control this variation."} {"id": "PMID:1259701", "title": "Genetics of lucilin, a storage protein from the sheep blowfly, Lucilia cuprina (Calliphoridae).", "content": "Lucilin, the main storage protein of larval fat body and hemolymph in the sheep blowfly, Lucilia cuprina, has been isolated as a series of trimers composed of subunits of 83,000 +/- 5%, daltons. Extensive electrophoretically detectable polymorphism of lucilin subunit patterns occurs in wild and laboratory populations of Lucilia; from four to nine bands are seen in any one individual. Evidence from genetic, electrophoretic, immunological, and structural studies suggests the existence of a series of 12 or more closely related structural loci (designated Luc-1 to Luc-12) which may have arisen through gene duplication. Codominant allelic variation has been found at several of these loci. Luc-1 and Luc-3, and probably the other structural loci of the series, are located on chromosome 2.", "contents": "Genetics of lucilin, a storage protein from the sheep blowfly, Lucilia cuprina (Calliphoridae). Lucilin, the main storage protein of larval fat body and hemolymph in the sheep blowfly, Lucilia cuprina, has been isolated as a series of trimers composed of subunits of 83,000 +/- 5%, daltons. Extensive electrophoretically detectable polymorphism of lucilin subunit patterns occurs in wild and laboratory populations of Lucilia; from four to nine bands are seen in any one individual. Evidence from genetic, electrophoretic, immunological, and structural studies suggests the existence of a series of 12 or more closely related structural loci (designated Luc-1 to Luc-12) which may have arisen through gene duplication. Codominant allelic variation has been found at several of these loci. Luc-1 and Luc-3, and probably the other structural loci of the series, are located on chromosome 2."} {"id": "PMID:1259702", "title": "Gene action in fish of tetraploid origin. III. Ribosomal DNA amount in cyprinid fish.", "content": "Phylogenetically diploid and tetraploid cyprinid fish species have cells of very similar volumes and protein contents. This finding has prompted us to postulate a regulatory system established during the evolution of the tetraploids leading to a diploid state of genic expression. It was proposed that this might be accounted for by a selective loss of ribosomal genes. RNA-DNA hybridization experiments, however, reveal a clear-cut 1:2 relationship of ribosomal DNA amounts between the diploid and the tetraploid species.", "contents": "Gene action in fish of tetraploid origin. III. Ribosomal DNA amount in cyprinid fish. Phylogenetically diploid and tetraploid cyprinid fish species have cells of very similar volumes and protein contents. This finding has prompted us to postulate a regulatory system established during the evolution of the tetraploids leading to a diploid state of genic expression. It was proposed that this might be accounted for by a selective loss of ribosomal genes. RNA-DNA hybridization experiments, however, reveal a clear-cut 1:2 relationship of ribosomal DNA amounts between the diploid and the tetraploid species."} {"id": "PMID:1259703", "title": "Polymorphism of transferrin in carp (Cyprinus carpio L.): genetic determination, isolation, and partial characterization.", "content": "Seven transferrin variants (A,B,C,D,E,F, and G) have been found in carp sera (Cyprinus carpio L.). Genetic analysis involves five variants and agrees with the hypothesis of simple codominant autosomal inheritance at one transferrin (Tf) locus in spite of the fact that the carp is a tetraploid in relation to other species of the same family. Carp populations from three regions were studied which differed in gene frequencies. Individual populations were in Hardy-Weinberg equilibrium. The polymorphism of carp transferrins can be used for the identification of offspring of single parent pairs, stocked in one pond. Transferrins have been isolated and characterized. Homozygous phenotypes comprised four iron-binding components differing in electrophoretic mobility. This heterogeneity is not caused by sialic acid, which is absent. Amino acid composition, content of hexoses (1 mole/mole of protein) and hexosamines (1 mole/mole of protein), molecualr weight (70,000), and the isoelectric point (5.0) have been determined. No N-terminal amino acid could be detected.", "contents": "Polymorphism of transferrin in carp (Cyprinus carpio L.): genetic determination, isolation, and partial characterization. Seven transferrin variants (A,B,C,D,E,F, and G) have been found in carp sera (Cyprinus carpio L.). Genetic analysis involves five variants and agrees with the hypothesis of simple codominant autosomal inheritance at one transferrin (Tf) locus in spite of the fact that the carp is a tetraploid in relation to other species of the same family. Carp populations from three regions were studied which differed in gene frequencies. Individual populations were in Hardy-Weinberg equilibrium. The polymorphism of carp transferrins can be used for the identification of offspring of single parent pairs, stocked in one pond. Transferrins have been isolated and characterized. Homozygous phenotypes comprised four iron-binding components differing in electrophoretic mobility. This heterogeneity is not caused by sialic acid, which is absent. Amino acid composition, content of hexoses (1 mole/mole of protein) and hexosamines (1 mole/mole of protein), molecualr weight (70,000), and the isoelectric point (5.0) have been determined. No N-terminal amino acid could be detected."} {"id": "PMID:1259704", "title": "Genetic studies of murine catalase: regulation of multiple molecular forms of kidney catalase.", "content": "Starch gel electrophoresis of kidney catalase in inbred strains C3H and C57BL/6, their F1 hybrid, and first and second backcross generations demonstrated that single-component (type A) v. multiple-component (type B) electrophoretic patterns are controlled by a single locus. The type A electrophoretic pattern is dominant. Twenty-five inbred strains of mice were classified according to their kidney catalase electrophoretic pattern. The data indicate that the segregating genetic factor determines a specific substance in the type A kidney which affects the electrophoretic mobility of catalase. A comparison of the F1 hybrid enzyme with a 1:1 mixture of C3H and C57BL/6 enzyme showed that the alteration of electrophoretic mobility is the result of posttranslational modification of the catalase molecule. An association of kidney catalase electrophoretic pattern and the H-2kappa haplotype indicates that the locus controlling the electrophoretic pattern is most likely located on chromosome 17 in close proximity to the H-2 complex.", "contents": "Genetic studies of murine catalase: regulation of multiple molecular forms of kidney catalase. Starch gel electrophoresis of kidney catalase in inbred strains C3H and C57BL/6, their F1 hybrid, and first and second backcross generations demonstrated that single-component (type A) v. multiple-component (type B) electrophoretic patterns are controlled by a single locus. The type A electrophoretic pattern is dominant. Twenty-five inbred strains of mice were classified according to their kidney catalase electrophoretic pattern. The data indicate that the segregating genetic factor determines a specific substance in the type A kidney which affects the electrophoretic mobility of catalase. A comparison of the F1 hybrid enzyme with a 1:1 mixture of C3H and C57BL/6 enzyme showed that the alteration of electrophoretic mobility is the result of posttranslational modification of the catalase molecule. An association of kidney catalase electrophoretic pattern and the H-2kappa haplotype indicates that the locus controlling the electrophoretic pattern is most likely located on chromosome 17 in close proximity to the H-2 complex."} {"id": "PMID:1259705", "title": "Structural differences between albumin A and albumin C of the house mouse, Mus musculus.", "content": "Two albumins, albumin A from C3H mice and albumin C isolated from descendents of the wild mice in which the variant was first uncovered, were found to differ in their electrophoretic properties. Albumin C was shown to bind two more H+ ions than albumin A at pH 5.4. Peptide mapping after trypsin digestion revealed that albumin C had three peptides (TP-C1, TP-C2, and TP-C3) which were missing in albumin A. The latter likewise had a peptide (TP-A1) which was not found in albumin C. An amino acid analysis of the variant peptides suggests that TP-A1 had been split into TP-C1 and TP-C2 on digestion with trypsin, because a glutamic acid in TP-A1 was replaced by a lysine. This change would also appropriately alter the electrophoretic properties of albumin C. No obvious counterpart was discovered for TP-C3 of albumin C in albumin A.", "contents": "Structural differences between albumin A and albumin C of the house mouse, Mus musculus. Two albumins, albumin A from C3H mice and albumin C isolated from descendents of the wild mice in which the variant was first uncovered, were found to differ in their electrophoretic properties. Albumin C was shown to bind two more H+ ions than albumin A at pH 5.4. Peptide mapping after trypsin digestion revealed that albumin C had three peptides (TP-C1, TP-C2, and TP-C3) which were missing in albumin A. The latter likewise had a peptide (TP-A1) which was not found in albumin C. An amino acid analysis of the variant peptides suggests that TP-A1 had been split into TP-C1 and TP-C2 on digestion with trypsin, because a glutamic acid in TP-A1 was replaced by a lysine. This change would also appropriately alter the electrophoretic properties of albumin C. No obvious counterpart was discovered for TP-C3 of albumin C in albumin A."} {"id": "PMID:1259706", "title": "Alcohol dehydrogenase of Biomphalaria glabrata (Molusca: Pulmonata): polymorphism, genetic analysis, and interspecific variations.", "content": "Alcohol dehydrogenase of Biomphalaria glabrata has been characterized by electrophoresis, substrate specificities, and other physiochemical means. It exists as a multiple molecular form possessing a minimum number of three bands in ovotestis, five in digestive gland, and six in albumen gland. Each organ shows characteristic electrophoretic forms which differ in substrate specificities and the response to the organomercurial inhibitor p-hydroxymercuribenzoate. Mercaptoethanol treatment has no effect on any electrophoretic form. Genetic analyses of the electrophoretic variants show that three different loci are responsible for the synthesis of the various electrophoretic forms observed in this species. Different species vary in their electrophoretic patterns. A possible role of alcohol dehydrogenase isozymes in the phylogenetic relationship among three species, B. glabrata, B. tenagophila, and B. straminea, has been discussed.", "contents": "Alcohol dehydrogenase of Biomphalaria glabrata (Molusca: Pulmonata): polymorphism, genetic analysis, and interspecific variations. Alcohol dehydrogenase of Biomphalaria glabrata has been characterized by electrophoresis, substrate specificities, and other physiochemical means. It exists as a multiple molecular form possessing a minimum number of three bands in ovotestis, five in digestive gland, and six in albumen gland. Each organ shows characteristic electrophoretic forms which differ in substrate specificities and the response to the organomercurial inhibitor p-hydroxymercuribenzoate. Mercaptoethanol treatment has no effect on any electrophoretic form. Genetic analyses of the electrophoretic variants show that three different loci are responsible for the synthesis of the various electrophoretic forms observed in this species. Different species vary in their electrophoretic patterns. A possible role of alcohol dehydrogenase isozymes in the phylogenetic relationship among three species, B. glabrata, B. tenagophila, and B. straminea, has been discussed."} {"id": "PMID:1259707", "title": "Dissociation-recombination of intergenic sunflower alcohol dehydrogenase isozymes and relative isozyme activities.", "content": "Two unlinked genes, Adh1 and Adh2, control of the production of alcohol dehydrogenase (ADH) in seeds of the animal sunflower (Helianthus annuus). Each gene is polymorphic, having F and S alleles. Starch gel electrophoretic zymograms of the four possible double homozygotes have three bands, representing two homodimers and an intermediately migrating intergenic isozyme. Zymograms of double heterozygotes consist of nine bands produced by ten isozymes: six intragenics and four intergenics, two of which are coincident. Results of dissociation-recombination (D-R) experiments are reported which demonstrate the subunit composition of the intergenic isozymes, thus supporting the relationships suggested by genetic studies. Densitometric tracings of the zymogram of a cleared gel and measurements of activities of homodimer isozymes eluted from gels follwoing D-R of an intergenic isozyme showed that the Adh2 isozymes were more that twice as active as those of Adh1. Measurements of activities of crude extracts from the four possible double homozygous genotypes indicated that the seeds of the genotype Adh1F/Adh2F, Adh2S/Adh2S produced more activity than the other three. This genotype is the most common one found in wild and cultivated stocks. Isozymes eluted following electrophoresis of the same extracts had averages of 19%, 70%, and 11% of total activity contributed by the Adh1, Adh2, and intergeneic isozymes, respectively. A simple but efficient method of isozyme elution from starch gels is described which resulted in nearly full expected recovery (approximately 46%) of the ADH activity in the applied sample.", "contents": "Dissociation-recombination of intergenic sunflower alcohol dehydrogenase isozymes and relative isozyme activities. Two unlinked genes, Adh1 and Adh2, control of the production of alcohol dehydrogenase (ADH) in seeds of the animal sunflower (Helianthus annuus). Each gene is polymorphic, having F and S alleles. Starch gel electrophoretic zymograms of the four possible double homozygotes have three bands, representing two homodimers and an intermediately migrating intergenic isozyme. Zymograms of double heterozygotes consist of nine bands produced by ten isozymes: six intragenics and four intergenics, two of which are coincident. Results of dissociation-recombination (D-R) experiments are reported which demonstrate the subunit composition of the intergenic isozymes, thus supporting the relationships suggested by genetic studies. Densitometric tracings of the zymogram of a cleared gel and measurements of activities of homodimer isozymes eluted from gels follwoing D-R of an intergenic isozyme showed that the Adh2 isozymes were more that twice as active as those of Adh1. Measurements of activities of crude extracts from the four possible double homozygous genotypes indicated that the seeds of the genotype Adh1F/Adh2F, Adh2S/Adh2S produced more activity than the other three. This genotype is the most common one found in wild and cultivated stocks. Isozymes eluted following electrophoresis of the same extracts had averages of 19%, 70%, and 11% of total activity contributed by the Adh1, Adh2, and intergeneic isozymes, respectively. A simple but efficient method of isozyme elution from starch gels is described which resulted in nearly full expected recovery (approximately 46%) of the ADH activity in the applied sample."} {"id": "PMID:1259708", "title": "The quantitative analysis of ligand binding and initial-rate data for allosteric and other complex enzyme mechanisms.", "content": "1. The eight methods for plotting enzyme kinetic data are classified and analysed, and it is shown how, in each case, it is only possible to obtain quantitative data on the coefficients of the lowest- and highest-degree terms in the rate equation. 2. The combinations of coefficients that are accessible experimentally from limiting slopes and intercepts at both low and high substrate concentration are stated for all the graphical methods and the precise effects of these on curve shape in different spaces is discussed. 3. Ambiguities arising in the analysis of complex curves and certain special features are also investigated. 4. Four special ordering functions are defined and investigated and it is shown how knowledge of these allows a complete description of all possible complex curve shapes.", "contents": "The quantitative analysis of ligand binding and initial-rate data for allosteric and other complex enzyme mechanisms. 1. The eight methods for plotting enzyme kinetic data are classified and analysed, and it is shown how, in each case, it is only possible to obtain quantitative data on the coefficients of the lowest- and highest-degree terms in the rate equation. 2. The combinations of coefficients that are accessible experimentally from limiting slopes and intercepts at both low and high substrate concentration are stated for all the graphical methods and the precise effects of these on curve shape in different spaces is discussed. 3. Ambiguities arising in the analysis of complex curves and certain special features are also investigated. 4. Four special ordering functions are defined and investigated and it is shown how knowledge of these allows a complete description of all possible complex curve shapes."} {"id": "PMID:1259709", "title": "Purification and properties of pyruvate kinase from the hepatopancreas of Carcinus maenas.", "content": "Pyruvatekinase from the hepatopancreas of the common shore crab, Carcinus maenas, was purified to a specific activity of 240 units/mg of protein in the assay conditions described. 2. In one method of purification the enzymic activity could be resolved into two fractions after chromatography on DEAE-cellulose. Fructose 1, 6-diphosphate was able to effect the conversion of one form (peak 1) into the second (peak 2). 3. In the presence of a saturating concentration of fructose 1, 6-diphosphate both forms of the enzyme were kinetically similar. 4. Polyacrylamide-gel electrophoresis of the enzyme 1 day after preparation showed a single protein band. On storage at least three protein bands became visible, all of which were associated with pyruvate kinase activity. 5. Chromatography of the enzyme on Sephadex G-200 indicated a mol.wt. of 247000, but in the presence of fructose 1, 6-diphosphate the elution volume of the enzyme increased corresponding to a mol.wt. of 193000. 6 Dissociation of the enzyme in sodium dodecyl sulphate and 2-mercaptoethanol followed by polyacrylamide-gel electrophoresis produced one major protein band with a mol.wt. of 55000.", "contents": "Purification and properties of pyruvate kinase from the hepatopancreas of Carcinus maenas. Pyruvatekinase from the hepatopancreas of the common shore crab, Carcinus maenas, was purified to a specific activity of 240 units/mg of protein in the assay conditions described. 2. In one method of purification the enzymic activity could be resolved into two fractions after chromatography on DEAE-cellulose. Fructose 1, 6-diphosphate was able to effect the conversion of one form (peak 1) into the second (peak 2). 3. In the presence of a saturating concentration of fructose 1, 6-diphosphate both forms of the enzyme were kinetically similar. 4. Polyacrylamide-gel electrophoresis of the enzyme 1 day after preparation showed a single protein band. On storage at least three protein bands became visible, all of which were associated with pyruvate kinase activity. 5. Chromatography of the enzyme on Sephadex G-200 indicated a mol.wt. of 247000, but in the presence of fructose 1, 6-diphosphate the elution volume of the enzyme increased corresponding to a mol.wt. of 193000. 6 Dissociation of the enzyme in sodium dodecyl sulphate and 2-mercaptoethanol followed by polyacrylamide-gel electrophoresis produced one major protein band with a mol.wt. of 55000."} {"id": "PMID:1259710", "title": "Quantitative determination of N-terminal amino acids of peptides and proteins with cobalt(III) chelates.", "content": "Quantitative N-terminal peptide-bond hydrolysis with the cis-beta-hydroxyaquo(triethylenetetramine) cobal (III) ion, i.e. beta-[Co(trien)(OH)(OH2)]2+, is reported. The method has been demonstrated with 20 small peptides, a hexapeptide, bradykinin, insulin A chain (oxidized), glucagon and insulin. The procedure involves no acidic hydrolysis step and thus no destruction of labile amino acids.", "contents": "Quantitative determination of N-terminal amino acids of peptides and proteins with cobalt(III) chelates. Quantitative N-terminal peptide-bond hydrolysis with the cis-beta-hydroxyaquo(triethylenetetramine) cobal (III) ion, i.e. beta-[Co(trien)(OH)(OH2)]2+, is reported. The method has been demonstrated with 20 small peptides, a hexapeptide, bradykinin, insulin A chain (oxidized), glucagon and insulin. The procedure involves no acidic hydrolysis step and thus no destruction of labile amino acids."} {"id": "PMID:1259711", "title": "High-angle electron diffraction of frozen hydrated collagen.", "content": "By using the techniques developed by Taylor et al. [(1975) J. Mol. Biol. 92, 165-167] (freezing of the hydrated specimen before its insertion into the electron microscope and keeping it frozen throughout the diffraction experiment), it was possible to obtain a high-angle electron-diffraction pattern from collagen fibrils. This pattern is in good agreement with that obtained by high-angle X-ray diffraction. Electron diffraction will be very useful to study collagen, because the diffraction pattern from a carefully selected area of one fibril is now feasible.", "contents": "High-angle electron diffraction of frozen hydrated collagen. By using the techniques developed by Taylor et al. [(1975) J. Mol. Biol. 92, 165-167] (freezing of the hydrated specimen before its insertion into the electron microscope and keeping it frozen throughout the diffraction experiment), it was possible to obtain a high-angle electron-diffraction pattern from collagen fibrils. This pattern is in good agreement with that obtained by high-angle X-ray diffraction. Electron diffraction will be very useful to study collagen, because the diffraction pattern from a carefully selected area of one fibril is now feasible."} {"id": "PMID:1259713", "title": "The N-terminal amino acid sequence of plastocyanin from Stellaria media L. An exercise to establish criteria for the identification of residues from a sequenator.", "content": "The N-terminal amino acid sequence of plastocyanin from Stellaria media L. (chickweed) has been determined by means of an automatic sequencer. Amino acid derivatives obtained during the degradation were identified by a combination of t.l.c., g.l.c. and regeneration of the parent amino acid. The analytical results are presented for each sample, and the criteria used to establish the amino acid sequence are discussed.", "contents": "The N-terminal amino acid sequence of plastocyanin from Stellaria media L. An exercise to establish criteria for the identification of residues from a sequenator. The N-terminal amino acid sequence of plastocyanin from Stellaria media L. (chickweed) has been determined by means of an automatic sequencer. Amino acid derivatives obtained during the degradation were identified by a combination of t.l.c., g.l.c. and regeneration of the parent amino acid. The analytical results are presented for each sample, and the criteria used to establish the amino acid sequence are discussed."} {"id": "PMID:1259714", "title": "A phospholipid-deacylating system of bacteria active in a frozen medium.", "content": "A phosphatidylcholine-deacylating system present in a Butyrivibrio species (probably fibrisolvens) shows appreciable activity at low temperatures with a maximum hydrolysis rate at--10 degrees C. 2. The rate at--10 degrees C is higher than at 39 degrees C unless the system at the latter temperature is stimulated by adding oleic acid or sodium dodecyl sulphate. 3. The low-temperature phospholipase activity has an absolute requirement for thiol reagents, e.g. cysteine, dithiothreitol or mercaptoethanol. 4. Ca2+, Mg2+ and Mn2+ stimulate the activity up to 10 mM, but EDTA inhibits; higher concentrations of Ca2+ also inhibit. 5. The enhancement of activity at low temperatures appears not to be associated with a crystalline change in the hydrated phospholipid substrate, but depends on the formation of a solid phase in the incubation medium which brings the substrate and bacterial cells into juxtaposition or causes fusion.", "contents": "A phospholipid-deacylating system of bacteria active in a frozen medium. A phosphatidylcholine-deacylating system present in a Butyrivibrio species (probably fibrisolvens) shows appreciable activity at low temperatures with a maximum hydrolysis rate at--10 degrees C. 2. The rate at--10 degrees C is higher than at 39 degrees C unless the system at the latter temperature is stimulated by adding oleic acid or sodium dodecyl sulphate. 3. The low-temperature phospholipase activity has an absolute requirement for thiol reagents, e.g. cysteine, dithiothreitol or mercaptoethanol. 4. Ca2+, Mg2+ and Mn2+ stimulate the activity up to 10 mM, but EDTA inhibits; higher concentrations of Ca2+ also inhibit. 5. The enhancement of activity at low temperatures appears not to be associated with a crystalline change in the hydrated phospholipid substrate, but depends on the formation of a solid phase in the incubation medium which brings the substrate and bacterial cells into juxtaposition or causes fusion."} {"id": "PMID:1259715", "title": "Isolation, composition and reactivity of the neutral glycoproteins from human meconiums with specificities of the ABO and Lewis systems.", "content": "Blood-group-specific A1, B, AB, H and Lea neutral glycoproteins were isolated from suitable pools of human normal meconiums by a preliminary fractionation with a cationic detergent at pH5 and 9 (borate), followed by ion-exchange and gel chromatography. The ABH materials have sedimentation coefficients of about 10S-11S, whereas the Lea preparation, not strictly homogeneous, shows a coefficient of 7S. From the detailed analytical data collected, the following relations are deduced between these various substances; they all possess a common peptide core; there are stable ratios of N-acetylglucosamine/N-acetylgalactosamine in the B, H and Lea materials and of N-acetylglucosamine/galactose in A, H and Lea materials, from which the numbers of A and B determinants are estimated. In the ABH substances, the ratio of glucosamine to the sum of threonine and serine is stable. Presumably because of genetic factors, the amount of fucose varies among the different glycoproteins, but it is always definitely lower than in the average cyst substances. Various serological tests and precipitin methods were used to measure the potency, purity and integrity of the preparations, including comparisons between A1 and A2 substances from this source. The Leb activity did not appear as high as it is in glycoproteins from adults and a possible interpretation would be the immature Lewis system as observed on erythrocytes; this could explain their very strong inhibiting power towards iso-agglutinins. This family of substances with various specificities has common features with that prepared from ovarian cysts, but differs clearly on some points.", "contents": "Isolation, composition and reactivity of the neutral glycoproteins from human meconiums with specificities of the ABO and Lewis systems. Blood-group-specific A1, B, AB, H and Lea neutral glycoproteins were isolated from suitable pools of human normal meconiums by a preliminary fractionation with a cationic detergent at pH5 and 9 (borate), followed by ion-exchange and gel chromatography. The ABH materials have sedimentation coefficients of about 10S-11S, whereas the Lea preparation, not strictly homogeneous, shows a coefficient of 7S. From the detailed analytical data collected, the following relations are deduced between these various substances; they all possess a common peptide core; there are stable ratios of N-acetylglucosamine/N-acetylgalactosamine in the B, H and Lea materials and of N-acetylglucosamine/galactose in A, H and Lea materials, from which the numbers of A and B determinants are estimated. In the ABH substances, the ratio of glucosamine to the sum of threonine and serine is stable. Presumably because of genetic factors, the amount of fucose varies among the different glycoproteins, but it is always definitely lower than in the average cyst substances. Various serological tests and precipitin methods were used to measure the potency, purity and integrity of the preparations, including comparisons between A1 and A2 substances from this source. The Leb activity did not appear as high as it is in glycoproteins from adults and a possible interpretation would be the immature Lewis system as observed on erythrocytes; this could explain their very strong inhibiting power towards iso-agglutinins. This family of substances with various specificities has common features with that prepared from ovarian cysts, but differs clearly on some points."} {"id": "PMID:1259716", "title": "Carbohydrate composition of lymphocyte plasma membrane from pig mesenteric lymph node.", "content": "Pig lymphocyte plasma membrane isolated from mesenteric lymph node contained 69 mug of carbohydrate/mg dry wt., which was made up of neutral sugar, amino sugar and sialic acid in the molar proportions 5:1.7:1. The neutral sugar comprised fucose, ribose, mannose, glucose, galactose and inositol (molar proportions 2:9:11:15:26:1), and the amino sugar glucosamine and galactosamine (molar ratio 2:1). The ribose was most probably derived from RNA. All of the fucose and mannose and almost all of the glucosamine were associated with the membrane protein whereas the membrane lipid contained all of the inositol. The remaining sugars were distributed in various ratios between the protein and lipid fractions.", "contents": "Carbohydrate composition of lymphocyte plasma membrane from pig mesenteric lymph node. Pig lymphocyte plasma membrane isolated from mesenteric lymph node contained 69 mug of carbohydrate/mg dry wt., which was made up of neutral sugar, amino sugar and sialic acid in the molar proportions 5:1.7:1. The neutral sugar comprised fucose, ribose, mannose, glucose, galactose and inositol (molar proportions 2:9:11:15:26:1), and the amino sugar glucosamine and galactosamine (molar ratio 2:1). The ribose was most probably derived from RNA. All of the fucose and mannose and almost all of the glucosamine were associated with the membrane protein whereas the membrane lipid contained all of the inositol. The remaining sugars were distributed in various ratios between the protein and lipid fractions."} {"id": "PMID:1259717", "title": "Isolation, properties and amino acid sequences of three neurotoxins from the venom of a sea snake, Aipysurus laevis.", "content": "Aipysurus laevis venom was chromatographed on CM-cellulose and Bio-Rex 70 columns. Three neurotoxic components, toxins Aipysurus laevis a, b and c, were isolated. The toxins a, b and c corresponded to 22, 33 and 21% respectively of the proteins in the original venom, and accounted for almost all the lethal activity of the venom. The three toxins a, b and c were monodisperse on disc electrophoresis at pH4; toxins a and b moved at the same velocity and c a little faster. They were monodisperse also on sodium dodecyl sulphate-polyacrylamide-disc-gel electrophoresis, giving a molecular weight of 7600. The molecular weight of toxin b estimated by gel filtration was 7000. The amino acid sequence analyses of these toxins revealed that they consisted of 60 amino acid residues and that Aipysurus laevis b was [25-methionine, 28-arginine] Aipysurus laevis a. Aipysurus laevis c was [28-lysine] Aipysurus laevis a, the tryptic peptide sequence relying on homology. The LD50 values of these toxins for 20g mice were 0.076 mug/g body wt. They inhibited the acetylcholine-induced contracture but did not affect the CKl-induced contracture of the isolated muscle.", "contents": "Isolation, properties and amino acid sequences of three neurotoxins from the venom of a sea snake, Aipysurus laevis. Aipysurus laevis venom was chromatographed on CM-cellulose and Bio-Rex 70 columns. Three neurotoxic components, toxins Aipysurus laevis a, b and c, were isolated. The toxins a, b and c corresponded to 22, 33 and 21% respectively of the proteins in the original venom, and accounted for almost all the lethal activity of the venom. The three toxins a, b and c were monodisperse on disc electrophoresis at pH4; toxins a and b moved at the same velocity and c a little faster. They were monodisperse also on sodium dodecyl sulphate-polyacrylamide-disc-gel electrophoresis, giving a molecular weight of 7600. The molecular weight of toxin b estimated by gel filtration was 7000. The amino acid sequence analyses of these toxins revealed that they consisted of 60 amino acid residues and that Aipysurus laevis b was [25-methionine, 28-arginine] Aipysurus laevis a. Aipysurus laevis c was [28-lysine] Aipysurus laevis a, the tryptic peptide sequence relying on homology. The LD50 values of these toxins for 20g mice were 0.076 mug/g body wt. They inhibited the acetylcholine-induced contracture but did not affect the CKl-induced contracture of the isolated muscle."} {"id": "PMID:1259718", "title": "Investigation of ribonuclease-catalysed kinetics by a micro-calorimetric method.", "content": "A rapid micro-calorimetric method for the simultaneous determination of the Michaelis-Menten parameters and the enthalpy of enzymic reactions is developed. The hydrolysis of 2': 3'-cyclic CMP by ribonuclease A is studied to test the proposed method; values obtained are in good agreement with already published data. Enzymic hydrolysis of yeast RNA, unlike that of cyclic phosphates, is shown to be endothermic. This result is explained by the two-step mechanism of this reaction.", "contents": "Investigation of ribonuclease-catalysed kinetics by a micro-calorimetric method. A rapid micro-calorimetric method for the simultaneous determination of the Michaelis-Menten parameters and the enthalpy of enzymic reactions is developed. The hydrolysis of 2': 3'-cyclic CMP by ribonuclease A is studied to test the proposed method; values obtained are in good agreement with already published data. Enzymic hydrolysis of yeast RNA, unlike that of cyclic phosphates, is shown to be endothermic. This result is explained by the two-step mechanism of this reaction."} {"id": "PMID:1259792", "title": "Intraarticular activation of the complement system in patients with juvenile rheumatoid arthritis.", "content": "Analyses of CH50, complement components, properdin factors, and kininogen in synovial fluid of patients with juvenile rheumatoid arthritis revealed evidence of activation of the classic complement pathway in all clinical subgroups. Juveniles with the adult pattern of disease had the greatest incidence of complement abnormalities. Evaluation of individual components by both activity determination and protein measurement showed decreased synovial fluid specific functional activity (activity per microgram protein) to the more marked in synovial fluids with profound depressions of complement activity. These findings provide further evidence that nonfunctional, antigenically intact component protein may remain after complement activation. Radial immunodiffusion measurements of properdin factors and kininogen failed to support their involvement in joint inflammation. Serum complement component measurements by activity but not protein concentration correlated with other parameters or inflammation. Four patients had isolated depressions of serum C2 activity. Immunoglobulin levels, particularly IgA, correlated with some complement measurements and with the sedimentation rate.", "contents": "Intraarticular activation of the complement system in patients with juvenile rheumatoid arthritis. Analyses of CH50, complement components, properdin factors, and kininogen in synovial fluid of patients with juvenile rheumatoid arthritis revealed evidence of activation of the classic complement pathway in all clinical subgroups. Juveniles with the adult pattern of disease had the greatest incidence of complement abnormalities. Evaluation of individual components by both activity determination and protein measurement showed decreased synovial fluid specific functional activity (activity per microgram protein) to the more marked in synovial fluids with profound depressions of complement activity. These findings provide further evidence that nonfunctional, antigenically intact component protein may remain after complement activation. Radial immunodiffusion measurements of properdin factors and kininogen failed to support their involvement in joint inflammation. Serum complement component measurements by activity but not protein concentration correlated with other parameters or inflammation. Four patients had isolated depressions of serum C2 activity. Immunoglobulin levels, particularly IgA, correlated with some complement measurements and with the sedimentation rate."} {"id": "PMID:1259794", "title": "Metabolic changes in rabbit articular cartilage due to inflammation.", "content": "The effect of inflammation on the articular cartilage of rabbit knee joints were studied. The inflammation was induced by intraarticular injections of corton oil or rabbit peritoneal leukocyte lysates. An increase in the activities of various lysosomal enzymes was observed in the synovial fluid as well as in the cartilage of the inflamed joints. Loss of proteoglycans, increased rate of degradation of collagen and proteoglycans, and increased rate of their synthesis were evident in the treated cartilage. The rate of uptake of 3H-thymidine was also increased. A significant change was observed in the type of collagen synthesized by these explants in vitro. In addition to synthesizing their characteristics Type II collagen, the cartilage explants from the treated joints synthesized Type I collagen.", "contents": "Metabolic changes in rabbit articular cartilage due to inflammation. The effect of inflammation on the articular cartilage of rabbit knee joints were studied. The inflammation was induced by intraarticular injections of corton oil or rabbit peritoneal leukocyte lysates. An increase in the activities of various lysosomal enzymes was observed in the synovial fluid as well as in the cartilage of the inflamed joints. Loss of proteoglycans, increased rate of degradation of collagen and proteoglycans, and increased rate of their synthesis were evident in the treated cartilage. The rate of uptake of 3H-thymidine was also increased. A significant change was observed in the type of collagen synthesized by these explants in vitro. In addition to synthesizing their characteristics Type II collagen, the cartilage explants from the treated joints synthesized Type I collagen."} {"id": "PMID:1259793", "title": "The arthropathy of relapsing polychrondritis.", "content": "Twenty-three adults (11 males and 12 females) with well-defined relapsing polychondritis (RP) are studied in order to characterize the arthropathy of RP. Arthritis was found in 19 patients-as the presenting feature in 8 and as a significant symptom in 11 others. The usual pattern of involvement was migratory, asymmetric, non-nodular, nonerosive, and seronegative, and affected large and small joints as well as parasternal articulations. In addition RP was seen in 3 patients with preexisting chronic polyarthritis or associated rheuamtic disease.", "contents": "The arthropathy of relapsing polychrondritis. Twenty-three adults (11 males and 12 females) with well-defined relapsing polychondritis (RP) are studied in order to characterize the arthropathy of RP. Arthritis was found in 19 patients-as the presenting feature in 8 and as a significant symptom in 11 others. The usual pattern of involvement was migratory, asymmetric, non-nodular, nonerosive, and seronegative, and affected large and small joints as well as parasternal articulations. In addition RP was seen in 3 patients with preexisting chronic polyarthritis or associated rheuamtic disease."} {"id": "PMID:1259796", "title": "Deforming arthritis of the hands in polymyositis.", "content": "Arthritis of the hands with erosions, periosteal calcification, and interphalangeal thumb joint instability was seen in 6 patients with polymyositis. \"Overlap\" features such as Raynaud's phenomenon, positive LE clot test, and positive antinuclear antibody test were present, but clinically the primary disease was clearly polymyositis. This rather unusual constellation of roentgenographic findings strongly suggests the possibility of polymyositis.", "contents": "Deforming arthritis of the hands in polymyositis. Arthritis of the hands with erosions, periosteal calcification, and interphalangeal thumb joint instability was seen in 6 patients with polymyositis. \"Overlap\" features such as Raynaud's phenomenon, positive LE clot test, and positive antinuclear antibody test were present, but clinically the primary disease was clearly polymyositis. This rather unusual constellation of roentgenographic findings strongly suggests the possibility of polymyositis."} {"id": "PMID:1259795", "title": "Differentiation and characterization of autoantibodies and their antigens in Sj\u00f6gren's syndrome.", "content": "Autoantibodies in Sj\u00f6gren's syndrome (SS) were identified by their precipitin reactions with tissue antigens in immunodiffusion. The source of antigens was a sonicated extract of human lymphoid cells (WiI2) grown in tissue culture. Three distinct precipitin systems were identified and referred to as precipitins SS-A and SS-B, and rheumatoid arthritis precipitin. These studies show that precipitins SS-A and SS-B are present in high frequency in sera of patients with SS without associated rheuamtoid arthritis (RA) and are absent or present in low frequency in many other connective tissue diseases. On the other hand patients with SS who also had clinical features compatible with RA (SS-RA) did not have precipitins SS-A and SS-B but had rheumatoid arthritis precipitin (RAP). The latter precipitin was also present in RA patients in a similar order of frequency as in SS-RA. All three precipitin systems were shown to be reactions betweeen immunoglobulins and cellular antigens. The origin of SS-A and SS-B antigens was demonstrated by immunofluorescence to be primarily from the nucleus but the origin of RAP in the cell has not been established.", "contents": "Differentiation and characterization of autoantibodies and their antigens in Sj\u00f6gren's syndrome. Autoantibodies in Sj\u00f6gren's syndrome (SS) were identified by their precipitin reactions with tissue antigens in immunodiffusion. The source of antigens was a sonicated extract of human lymphoid cells (WiI2) grown in tissue culture. Three distinct precipitin systems were identified and referred to as precipitins SS-A and SS-B, and rheumatoid arthritis precipitin. These studies show that precipitins SS-A and SS-B are present in high frequency in sera of patients with SS without associated rheuamtoid arthritis (RA) and are absent or present in low frequency in many other connective tissue diseases. On the other hand patients with SS who also had clinical features compatible with RA (SS-RA) did not have precipitins SS-A and SS-B but had rheumatoid arthritis precipitin (RAP). The latter precipitin was also present in RA patients in a similar order of frequency as in SS-RA. All three precipitin systems were shown to be reactions betweeen immunoglobulins and cellular antigens. The origin of SS-A and SS-B antigens was demonstrated by immunofluorescence to be primarily from the nucleus but the origin of RAP in the cell has not been established."} {"id": "PMID:1259797", "title": "Histocompatibility antigens in systemic lupus erythematosus.", "content": "Histocompatibility (HL-A) antigens were determined in 120 patients with systemic lupus erythematosus (SLE) and 120 matched controls. Increased frequencies of HL-A1 and HL-A8 were found. HL-A1 was more strongly associated with SLE in black patients (71 patients), whereas HL-A8 was more impressively associated with SLE in white patients (49 patients). In addition HL-A1 appeared more frequently in those with early onset of disease in both races; and HL-A1, HL-A8, and the HL-A1,8 phenotype seemed to be associated with severe SLE (renal and central nervous system involvement) in white patients. These data support the proposal that there are genetic influences in the pathogenesis and expression of SLE.", "contents": "Histocompatibility antigens in systemic lupus erythematosus. Histocompatibility (HL-A) antigens were determined in 120 patients with systemic lupus erythematosus (SLE) and 120 matched controls. Increased frequencies of HL-A1 and HL-A8 were found. HL-A1 was more strongly associated with SLE in black patients (71 patients), whereas HL-A8 was more impressively associated with SLE in white patients (49 patients). In addition HL-A1 appeared more frequently in those with early onset of disease in both races; and HL-A1, HL-A8, and the HL-A1,8 phenotype seemed to be associated with severe SLE (renal and central nervous system involvement) in white patients. These data support the proposal that there are genetic influences in the pathogenesis and expression of SLE."} {"id": "PMID:1259798", "title": "Effect of aspirin on liver tests in patients with RA or SLE and in normal volunteers.", "content": "Aspirin was given to 20 patients with RA, 16 patients with SLE, and 3 normal volunteers. Four of the RA patients, 7 of the SLE patients, and 1 normal volunteer developed abnormal liver tests, during the study. The abnormalities (elevated transaminases) were most frequent and of rapid onset in patients with cliniclaly active SLE. Increases in BUN and creatinine related to aspirin were observed in several subjects. In a retrospective survey of 80 patients with SLE, aspirin appeared responsible for two-thirds of episodes of liver test abnormalities in 19 patients.", "contents": "Effect of aspirin on liver tests in patients with RA or SLE and in normal volunteers. Aspirin was given to 20 patients with RA, 16 patients with SLE, and 3 normal volunteers. Four of the RA patients, 7 of the SLE patients, and 1 normal volunteer developed abnormal liver tests, during the study. The abnormalities (elevated transaminases) were most frequent and of rapid onset in patients with cliniclaly active SLE. Increases in BUN and creatinine related to aspirin were observed in several subjects. In a retrospective survey of 80 patients with SLE, aspirin appeared responsible for two-thirds of episodes of liver test abnormalities in 19 patients."} {"id": "PMID:1259799", "title": "Clinical evaluation of benzbromarone: a new uricosuric drug.", "content": "The long-term efficacy and safety of benzbromarone were studied in 21 nontophaceous hyperuricemic men. Daily doses of 40 or 80 mg of micronized benzbromarone caused a rapid fall in plasma urate which was maintained throughout a study period that lasted up to 1 year. A concomitant marked increase in the clearance of urate indicated that benzbromarone is a potent uricosuric drug. Initial treatment was accompanied by transient hyperuricosuria, following which urinary uric acid reverted toward, but failed to reach completely, pretreatment values. Benzbromarone did not inhibit xanthine oxidase nor did it influence the activity of purine phosphoribosyl transferases. These observations suggest that benzbromarone has no direct effect upon purine metabolic pathways, but exerts its hypouricemic action solely by blocking tubular reabsorption of uric acid. Concomitant administration of aspirin interfered only slightly with the uricosuric properties of benzbromarone. No side effects directly attributable to the drug were observed.", "contents": "Clinical evaluation of benzbromarone: a new uricosuric drug. The long-term efficacy and safety of benzbromarone were studied in 21 nontophaceous hyperuricemic men. Daily doses of 40 or 80 mg of micronized benzbromarone caused a rapid fall in plasma urate which was maintained throughout a study period that lasted up to 1 year. A concomitant marked increase in the clearance of urate indicated that benzbromarone is a potent uricosuric drug. Initial treatment was accompanied by transient hyperuricosuria, following which urinary uric acid reverted toward, but failed to reach completely, pretreatment values. Benzbromarone did not inhibit xanthine oxidase nor did it influence the activity of purine phosphoribosyl transferases. These observations suggest that benzbromarone has no direct effect upon purine metabolic pathways, but exerts its hypouricemic action solely by blocking tubular reabsorption of uric acid. Concomitant administration of aspirin interfered only slightly with the uricosuric properties of benzbromarone. No side effects directly attributable to the drug were observed."} {"id": "PMID:1259800", "title": "Fibrinogen catabolism in systemic lupus erythematosus.", "content": "Because there is mounting evidence that localized intravascular coagulation may contribute to tissue injury following a variety of immunologic events, including immune complex diseases, fibrinogen catabolism was studied in patients with systemic lupus erythematosus to determine factors correlating with accelerated coagulation. 125I-fibrinogen half-life in controls was 90.1+/- 11 hours and the mean SLE half-life was 60.5 +/- 12. SLE patients in complete clinical remission had normal half-lives, but patients with symptomatic clinical disease, including renal disease, had significantly reduced fibrinogen survival. Accelerated fibrinogen consumption also correlated with positive tests for anti-DNA antibodies, but not with hypocomplementemia. These observations support the hypothesis that the coagulation system is activated in patients with immune complex diseases. Further studies are required to define the role, if any, that coagulation may play in causing tissue injury.", "contents": "Fibrinogen catabolism in systemic lupus erythematosus. Because there is mounting evidence that localized intravascular coagulation may contribute to tissue injury following a variety of immunologic events, including immune complex diseases, fibrinogen catabolism was studied in patients with systemic lupus erythematosus to determine factors correlating with accelerated coagulation. 125I-fibrinogen half-life in controls was 90.1+/- 11 hours and the mean SLE half-life was 60.5 +/- 12. SLE patients in complete clinical remission had normal half-lives, but patients with symptomatic clinical disease, including renal disease, had significantly reduced fibrinogen survival. Accelerated fibrinogen consumption also correlated with positive tests for anti-DNA antibodies, but not with hypocomplementemia. These observations support the hypothesis that the coagulation system is activated in patients with immune complex diseases. Further studies are required to define the role, if any, that coagulation may play in causing tissue injury."} {"id": "PMID:1259801", "title": "Antigenic profile of the rat chondrocyte.", "content": "Hetero- and alloantisera were obtained following hyperimmunization of nonsensitized New Zealand rabbits and dark agouti (DA) rats with washed chondrocytes which had been enzymatically isolated from the long bone cartilage of 17-19-day-old rat fetuses of the Fischer strain. Analyses of these antisera by PVP hemagglutination, dye-exclusion cytotoxicity, and indirect immunofluorescence indicated the presence of major histocompatibility antigens, as well as tissue-specific antigens on chronrocytes. Serologic specificity of reactions was demonstrated by serum absorptions and appropriate controls. These findings supprot previous work suggesting that chrondrocytes are endowed with major histocompatibility antigens. The significance of these findings in relation to rheumatoid arthritis is discussed.", "contents": "Antigenic profile of the rat chondrocyte. Hetero- and alloantisera were obtained following hyperimmunization of nonsensitized New Zealand rabbits and dark agouti (DA) rats with washed chondrocytes which had been enzymatically isolated from the long bone cartilage of 17-19-day-old rat fetuses of the Fischer strain. Analyses of these antisera by PVP hemagglutination, dye-exclusion cytotoxicity, and indirect immunofluorescence indicated the presence of major histocompatibility antigens, as well as tissue-specific antigens on chronrocytes. Serologic specificity of reactions was demonstrated by serum absorptions and appropriate controls. These findings supprot previous work suggesting that chrondrocytes are endowed with major histocompatibility antigens. The significance of these findings in relation to rheumatoid arthritis is discussed."} {"id": "PMID:1259802", "title": "Carpal arthritis with ankylosis in late onset Still's disease.", "content": "Thirteen patients are described in whom Still's disease began after age 15. All had objective evidence of arthritis, and 10 developed chronic synovitis of larger joints, especially the wrists. A characteristic evolution of roentgenographic changes was observed in 7 patients. Carpometacarpal and intercarpal joint spaces became selectively narrowed without erosions, and bony ankylosis eventually occurred. These roentgenographic changes may be a valuable clue to the diagnosis of Still's disease, regardless of the age at onset.", "contents": "Carpal arthritis with ankylosis in late onset Still's disease. Thirteen patients are described in whom Still's disease began after age 15. All had objective evidence of arthritis, and 10 developed chronic synovitis of larger joints, especially the wrists. A characteristic evolution of roentgenographic changes was observed in 7 patients. Carpometacarpal and intercarpal joint spaces became selectively narrowed without erosions, and bony ankylosis eventually occurred. These roentgenographic changes may be a valuable clue to the diagnosis of Still's disease, regardless of the age at onset."} {"id": "PMID:1259808", "title": "[Metabolism and effects of phosphorus in eutrophic infants dehydrated from diarrhea].", "content": "To verify whether there is a state of phosphate depletion in dehydrated infants with diarrhea and whether phosphate administration affects recovery from metabolic acidosis, two groups of infants were studied. All were males, from 1 to 7 months old, and in good nutritional state. The control group was treated with a standard regimen of I.V. fluids initially, followed by feedings of a diluted milk formula starting on the 2nd day of treatment. The study group, in addition to this standard regimen, received sodium phosphate (Na2HPO4/Na2HPO4, 4:1, pH 7.4), initially by the I.V. route and thereafter orally with the feedings, at the dose of 2mM/kg/day. During the first 6 days of treatment, daily electrolyte (Na, K, Ca, Mg. Cl and P) and nitrogen balances were recorded. Hydrogen ion excretion (NH4 + TA--HCO3) was determined daily. Clinical findings and course were similar in the two groups. No untoward effects were observed with phosphate administration. In the control group, P balance was negative during all the periods and losses were in excess of those expected from nitrogen losses, thus suggesting a state of depletion. In the P-treated group however, P retention was not demonstrated in the first 2 days, finding a not suggestive of a P depleted state. Linear regressions between both daily and cumulative balances of P-nitrogen-free and Ca indicated a close correlation, thus suggesting that these two ions are mobilized concommitantly.", "contents": "[Metabolism and effects of phosphorus in eutrophic infants dehydrated from diarrhea]. To verify whether there is a state of phosphate depletion in dehydrated infants with diarrhea and whether phosphate administration affects recovery from metabolic acidosis, two groups of infants were studied. All were males, from 1 to 7 months old, and in good nutritional state. The control group was treated with a standard regimen of I.V. fluids initially, followed by feedings of a diluted milk formula starting on the 2nd day of treatment. The study group, in addition to this standard regimen, received sodium phosphate (Na2HPO4/Na2HPO4, 4:1, pH 7.4), initially by the I.V. route and thereafter orally with the feedings, at the dose of 2mM/kg/day. During the first 6 days of treatment, daily electrolyte (Na, K, Ca, Mg. Cl and P) and nitrogen balances were recorded. Hydrogen ion excretion (NH4 + TA--HCO3) was determined daily. Clinical findings and course were similar in the two groups. No untoward effects were observed with phosphate administration. In the control group, P balance was negative during all the periods and losses were in excess of those expected from nitrogen losses, thus suggesting a state of depletion. In the P-treated group however, P retention was not demonstrated in the first 2 days, finding a not suggestive of a P depleted state. Linear regressions between both daily and cumulative balances of P-nitrogen-free and Ca indicated a close correlation, thus suggesting that these two ions are mobilized concommitantly."} {"id": "PMID:1259809", "title": "[Height of children with G. lamblia and there capacity to absorb d-xylose].", "content": "The investigation was carried out with the purpose of studying the capacity to absorb d-xylose in children with G. lamblia establishing also, whether or not their height was reduced. The study is included 25 school age children with giardiasis, pairing them according to sex and age with another 25 without intestinal parasitosis.", "contents": "[Height of children with G. lamblia and there capacity to absorb d-xylose]. The investigation was carried out with the purpose of studying the capacity to absorb d-xylose in children with G. lamblia establishing also, whether or not their height was reduced. The study is included 25 school age children with giardiasis, pairing them according to sex and age with another 25 without intestinal parasitosis."} {"id": "PMID:1259810", "title": "[Electroencephalogram in children during wakefulness and during induced sleep].", "content": "With the purpose of determining the advantages obtained in the electroencephalographic diagnoses of different clinical conditions, 567 electroencephalograms were practiced to 276 patients from the outpatient service of the Hospital Infantil de M\u00e9xico of different ages and clinical diagnoses during various stages of wakefulness, spontaneous or sleeping induced with chlorous hydrate and nembutal. In comparative studies carried out under induced sleeping, it was found that bioelectrical abnormalities showed up in a high percentage of the recording obtained during wakefulness, independently of age; thus, it is considered the ideal state. And in cases suggestive of hypsarrhythmia, or where asymmetries are investigated it is convenient to practice recordings under both conditions: wakefulness and sleep.", "contents": "[Electroencephalogram in children during wakefulness and during induced sleep]. With the purpose of determining the advantages obtained in the electroencephalographic diagnoses of different clinical conditions, 567 electroencephalograms were practiced to 276 patients from the outpatient service of the Hospital Infantil de M\u00e9xico of different ages and clinical diagnoses during various stages of wakefulness, spontaneous or sleeping induced with chlorous hydrate and nembutal. In comparative studies carried out under induced sleeping, it was found that bioelectrical abnormalities showed up in a high percentage of the recording obtained during wakefulness, independently of age; thus, it is considered the ideal state. And in cases suggestive of hypsarrhythmia, or where asymmetries are investigated it is convenient to practice recordings under both conditions: wakefulness and sleep."} {"id": "PMID:1259807", "title": "[Disseminated intravascular coagulation, 113 cases, including 17 children with fulminant purpura].", "content": "Between 1964 and 1971, 113 children with the syndrome of disseminated intravascular coagulation were studied at the Hospital Infantil de M\u00e9xico, including 17 cases with the diagnosis of fulminant purpura. Comparison was established with reports from foreign institutions. The following conclusions are offered: Fulminant purpura appears after a period of latency following the causal disease. It is not caused by septicemia; shows a clear picture in infants, preschool and school children, with letality index of 17.7%. In Mexico, DIC was caused by infection in 88% of the cases and in 68% of them, the infection started in the digestive tract. The diagnosis of fulminant purpura is based on the clinical picture, while in DIC, the diagnosis must also be based on laboratory tests unless one half of the diagnoses be missed.", "contents": "[Disseminated intravascular coagulation, 113 cases, including 17 children with fulminant purpura]. Between 1964 and 1971, 113 children with the syndrome of disseminated intravascular coagulation were studied at the Hospital Infantil de M\u00e9xico, including 17 cases with the diagnosis of fulminant purpura. Comparison was established with reports from foreign institutions. The following conclusions are offered: Fulminant purpura appears after a period of latency following the causal disease. It is not caused by septicemia; shows a clear picture in infants, preschool and school children, with letality index of 17.7%. In Mexico, DIC was caused by infection in 88% of the cases and in 68% of them, the infection started in the digestive tract. The diagnosis of fulminant purpura is based on the clinical picture, while in DIC, the diagnosis must also be based on laboratory tests unless one half of the diagnoses be missed."} {"id": "PMID:1259813", "title": "[Basic diet in the treatment of infants with prolonged diarrhea].", "content": "Fourteen infants between 1 and 9 months of age received elemental diet by continuous nasogastric drip. All had diarrhea (average duration 32 days). All were malnourished. Eight had carbohydrate intolerance. Two had intestinal pneumatosis. Elemental diet was used at first in 12.5% concentration and increased progressively until it reached a 25% concentration. Clinical response was favorably in every case.", "contents": "[Basic diet in the treatment of infants with prolonged diarrhea]. Fourteen infants between 1 and 9 months of age received elemental diet by continuous nasogastric drip. All had diarrhea (average duration 32 days). All were malnourished. Eight had carbohydrate intolerance. Two had intestinal pneumatosis. Elemental diet was used at first in 12.5% concentration and increased progressively until it reached a 25% concentration. Clinical response was favorably in every case."} {"id": "PMID:1259811", "title": "[Corticotherapy in hemangiomas].", "content": "A group of 17 patients with different types of hemangiomas that were submitted to treatment with steroids (prednisone) is studied. The results obtained are analyzed, together with the indications for the drug, its mechanism of action and the advantages of the doses used. Although this is not a definitive solution in all cases, considering the short number of complications observed, it is believed to be a treatment that be taken into account before more aggresive measures are followed, but it should never be done routinely.", "contents": "[Corticotherapy in hemangiomas]. A group of 17 patients with different types of hemangiomas that were submitted to treatment with steroids (prednisone) is studied. The results obtained are analyzed, together with the indications for the drug, its mechanism of action and the advantages of the doses used. Although this is not a definitive solution in all cases, considering the short number of complications observed, it is believed to be a treatment that be taken into account before more aggresive measures are followed, but it should never be done routinely."} {"id": "PMID:1259815", "title": "[Review of 70 cases of duodenal obstruction: diagnosis and treatment].", "content": "A review of 10 years (1964-1973) of patients admitted to the Hospital Infantil de Mexico with duodenal obstruction is made. There were 70 cases, 33 of which corresponded to intrinsic obstruction and 37 to the extrinsic type. The clinical picture, whether complete or incomplete obstruction is involved, is analysed and the importance of radiology is emphasized to reach an early diagnosis. The surgical management is described in accordance with the type of lesion found. Mortality in this type of pathology is still high in spite of the improvement in surgical techniques and intensive management of newborns, considering that these patients usually show low weight and a high frequency of associated malformations.", "contents": "[Review of 70 cases of duodenal obstruction: diagnosis and treatment]. A review of 10 years (1964-1973) of patients admitted to the Hospital Infantil de Mexico with duodenal obstruction is made. There were 70 cases, 33 of which corresponded to intrinsic obstruction and 37 to the extrinsic type. The clinical picture, whether complete or incomplete obstruction is involved, is analysed and the importance of radiology is emphasized to reach an early diagnosis. The surgical management is described in accordance with the type of lesion found. Mortality in this type of pathology is still high in spite of the improvement in surgical techniques and intensive management of newborns, considering that these patients usually show low weight and a high frequency of associated malformations."} {"id": "PMID:1259812", "title": "[Sinusitis in the child. Evaluation and indication for surgical treatment].", "content": "Sinusitis in children is a frequent problem in pediatric otorhinolaryngology. Medical treatment is often incomplete or inadequate, creating the need for proper surgical therapy. In a 3 year period (1972-1975), at the E.N.T. Dept. of the \"Hospital Infantil de M\u00e9xico\", a total of 51 patients, from 2 to 16 years age, underwent sinus surgery. The clinical diagnosis was completed with radiological and bacteriological studies. Chronic ethmoidal-maxillary and maxillary sinusitis were the most frequent types seen. Besides, considering E.N.T. sphere, other problems were present, mostly: tonsilloadenoiditis, important rhinoseptal deformity, and chronic otitis media. Also, dental caries, anemia, secondary to malnutrition and intestinal parasitosis, were additional frequent medical problems, among others. Allergic rhinosinusitis was suspected in at least 50% of them and clinically diagnosed in 15%. Bilateral nasoantral windows (antrostomy), and unilateral Caldwell-Luc procedure, were the surgical procedures most frequently performed. Adenoamygdalectomy, septorhinoplasty and mastoidectomy, were other frequent E.N.T. procedures. A total of 57% of the patients showed positive surgical findings at the time of sinus surgery; this is coincident with the work of other authors. Results of surgical and complementary medical management showed 39% of recovery rate. A high percentage of patients (31%), were lost to follow-up after initial surgery. The point of necessary conservative sinus surgery in children, is stressed in this paper.", "contents": "[Sinusitis in the child. Evaluation and indication for surgical treatment]. Sinusitis in children is a frequent problem in pediatric otorhinolaryngology. Medical treatment is often incomplete or inadequate, creating the need for proper surgical therapy. In a 3 year period (1972-1975), at the E.N.T. Dept. of the \"Hospital Infantil de M\u00e9xico\", a total of 51 patients, from 2 to 16 years age, underwent sinus surgery. The clinical diagnosis was completed with radiological and bacteriological studies. Chronic ethmoidal-maxillary and maxillary sinusitis were the most frequent types seen. Besides, considering E.N.T. sphere, other problems were present, mostly: tonsilloadenoiditis, important rhinoseptal deformity, and chronic otitis media. Also, dental caries, anemia, secondary to malnutrition and intestinal parasitosis, were additional frequent medical problems, among others. Allergic rhinosinusitis was suspected in at least 50% of them and clinically diagnosed in 15%. Bilateral nasoantral windows (antrostomy), and unilateral Caldwell-Luc procedure, were the surgical procedures most frequently performed. Adenoamygdalectomy, septorhinoplasty and mastoidectomy, were other frequent E.N.T. procedures. A total of 57% of the patients showed positive surgical findings at the time of sinus surgery; this is coincident with the work of other authors. Results of surgical and complementary medical management showed 39% of recovery rate. A high percentage of patients (31%), were lost to follow-up after initial surgery. The point of necessary conservative sinus surgery in children, is stressed in this paper."} {"id": "PMID:1259816", "title": "[Surgical management of presacral sacrococcygeal teratomas, or with intrapelvic extension].", "content": "Two cases of sacrococcygeal teratomas that were successfully treated surgically through the abdominosacral route are reported. Besides, a series of 36 children diagnosed through a period of 30 years is reviewed and considerations are made on the importance the classification of teratomas has, to choose the best route of approach for the surgical removal of these tumors. Mention is made of symptoms that allow the diagnosis of presacral teratomas and of those that show intrapelvic or abdominal extension.", "contents": "[Surgical management of presacral sacrococcygeal teratomas, or with intrapelvic extension]. Two cases of sacrococcygeal teratomas that were successfully treated surgically through the abdominosacral route are reported. Besides, a series of 36 children diagnosed through a period of 30 years is reviewed and considerations are made on the importance the classification of teratomas has, to choose the best route of approach for the surgical removal of these tumors. Mention is made of symptoms that allow the diagnosis of presacral teratomas and of those that show intrapelvic or abdominal extension."} {"id": "PMID:1259817", "title": "[Pyelonephritis and bacterial tubulointerstitial nephritis].", "content": "With the purpose of establishing the clinicopathologic correlation in pyelonephritis and to discard other interstitial nephrites, with present day morphologic criteria we analysed 63 casos that had been diagnosed as pyelonephritis, following Weiss and Parker's histologic criterion. The clinicopathologic diagnosis of pyelonephritis was confirmed in 12 cases; all of them showed obstructive uropathy and in most of them, there was chronic renal failure. Interstitial nephritis was established in 27 cases, all of them showing septicemia and almost half of the cases showed acute renal failure. Other 20 cases showed tubulointerstitial nephritis secondary to different types of glomerulopathies, fetal glomerulosclerosis, dysplasias, nephrophthisis, radiation nephritis and renal infarct. In 4 cases, the study of sections finer than the original, showed absence of histopathologic lesions. The results of the present study point out the main causes of confusion with the pathological diagnosis of pyelonephritis, the necessity to investigate predisposing uropathy in patients with urinary infection and stresses the importance to establish correlation with clinical and laboratory findings in cases with tubulointerstitial lesions.", "contents": "[Pyelonephritis and bacterial tubulointerstitial nephritis]. With the purpose of establishing the clinicopathologic correlation in pyelonephritis and to discard other interstitial nephrites, with present day morphologic criteria we analysed 63 casos that had been diagnosed as pyelonephritis, following Weiss and Parker's histologic criterion. The clinicopathologic diagnosis of pyelonephritis was confirmed in 12 cases; all of them showed obstructive uropathy and in most of them, there was chronic renal failure. Interstitial nephritis was established in 27 cases, all of them showing septicemia and almost half of the cases showed acute renal failure. Other 20 cases showed tubulointerstitial nephritis secondary to different types of glomerulopathies, fetal glomerulosclerosis, dysplasias, nephrophthisis, radiation nephritis and renal infarct. In 4 cases, the study of sections finer than the original, showed absence of histopathologic lesions. The results of the present study point out the main causes of confusion with the pathological diagnosis of pyelonephritis, the necessity to investigate predisposing uropathy in patients with urinary infection and stresses the importance to establish correlation with clinical and laboratory findings in cases with tubulointerstitial lesions."} {"id": "PMID:1259818", "title": "[Perinatal pathology].", "content": "The study includes 965 cases of autopsies in premature and full term newborns comparing their pathology within the pre, intra and postnatal periods; the neonatal period was also divided into weeks. The results may be correlated from different parameters, pointing out susceptibility, risk, nature of the pathologic processes and their order of arrival within the stages mentioned. The suitable reason that may exist to explain the high index of anatomoclinical diagnoses, not correlated in this study, is analysed and it is believed that a knowledge of some of these problems may be useful to prevent and to manage them adequately within and outside our hospital units.", "contents": "[Perinatal pathology]. The study includes 965 cases of autopsies in premature and full term newborns comparing their pathology within the pre, intra and postnatal periods; the neonatal period was also divided into weeks. The results may be correlated from different parameters, pointing out susceptibility, risk, nature of the pathologic processes and their order of arrival within the stages mentioned. The suitable reason that may exist to explain the high index of anatomoclinical diagnoses, not correlated in this study, is analysed and it is believed that a knowledge of some of these problems may be useful to prevent and to manage them adequately within and outside our hospital units."} {"id": "PMID:1259819", "title": "[Review of 1,172 clinical cases with human communication disorders].", "content": "The study comprised 1,172 clinical cases that were classified according to sex, age and speech disorders. A review is made on the most common alterations that they present, the selective treatment in each type and their rehabilitation.", "contents": "[Review of 1,172 clinical cases with human communication disorders]. The study comprised 1,172 clinical cases that were classified according to sex, age and speech disorders. A review is made on the most common alterations that they present, the selective treatment in each type and their rehabilitation."} {"id": "PMID:1259820", "title": "[Krabbe's leukodystrophy. Report of a case].", "content": "A case of Krabbe's leukodystrophy is reported in a male child 18 months old, with evolution of 12 months. The clinical, radiological, pathological and genetic studies are described. Besides, this case was the basis to review the topic of leukodystrophy and the corresponding literature, considering that this is an uncommon disease in our milieu.", "contents": "[Krabbe's leukodystrophy. Report of a case]. A case of Krabbe's leukodystrophy is reported in a male child 18 months old, with evolution of 12 months. The clinical, radiological, pathological and genetic studies are described. Besides, this case was the basis to review the topic of leukodystrophy and the corresponding literature, considering that this is an uncommon disease in our milieu."} {"id": "PMID:1259826", "title": "Change in symptoms of hypertensive patients after referral to hospital clinic.", "content": "At their first visit to a hospital clinic 178 patients referred with a diagnosis of hypertension were given a self-administered questionnaire. They received a similar questionnaire 12 months later. Of the 178 patients 99 were not initially on treatment. Similarly 78 normotensive subjects were drawn randomly from the local population and sent a second questionnaire 10 months later. The symptoms at the first visit of the normotensive controls, the untreated hypertensive patients, and 477 patients on long-term treatment in the hypertension clinic were compared. Treated and untreated hypertensive patients complained more of nocturia and also of unsteadiness either on standing or in the morning. Treated hypertensives complained more of sleepiness, dry mouth, diarrhoea, and, in men, impotence and failure of ejaculation. Similarly, untreated hypertensives complained of excessive depression, blurred vision, and waking headache. Fifty-five of the normotensive subjects and 110 of the newly referred hypertensive patients responded to the second questionnaire. The proportions losing and gaining symptoms were calculated together with the proportions always complaining and never complaining of a symptom. Hypertensive patients tended to lose the complaints of unsteadiness and headache but to gain the symptoms of vivid dreams, a slow walking pace, and diarrhoea. The net improvement for a symptom was defined as the excess of patients who lost a symptom over those who gained the symptom, expressed as a percentage. Over the follow-up period the control subjects had a net improvement averaged over 14 symptoms of +2-4 per cent. A similar result was obtained for the hypertensive patients of +2-0 per cent, the symptoms lost being balanced by those gained. The changes in symptoms with time were related to the changes in blood pressure and it is suggested that only headache, 'unsteadiness, lightheadedness, or faintness' and nocturia can actually result from raised blood pressure and then only in a proportion of patients complaining of these symptoms.", "contents": "Change in symptoms of hypertensive patients after referral to hospital clinic. At their first visit to a hospital clinic 178 patients referred with a diagnosis of hypertension were given a self-administered questionnaire. They received a similar questionnaire 12 months later. Of the 178 patients 99 were not initially on treatment. Similarly 78 normotensive subjects were drawn randomly from the local population and sent a second questionnaire 10 months later. The symptoms at the first visit of the normotensive controls, the untreated hypertensive patients, and 477 patients on long-term treatment in the hypertension clinic were compared. Treated and untreated hypertensive patients complained more of nocturia and also of unsteadiness either on standing or in the morning. Treated hypertensives complained more of sleepiness, dry mouth, diarrhoea, and, in men, impotence and failure of ejaculation. Similarly, untreated hypertensives complained of excessive depression, blurred vision, and waking headache. Fifty-five of the normotensive subjects and 110 of the newly referred hypertensive patients responded to the second questionnaire. The proportions losing and gaining symptoms were calculated together with the proportions always complaining and never complaining of a symptom. Hypertensive patients tended to lose the complaints of unsteadiness and headache but to gain the symptoms of vivid dreams, a slow walking pace, and diarrhoea. The net improvement for a symptom was defined as the excess of patients who lost a symptom over those who gained the symptom, expressed as a percentage. Over the follow-up period the control subjects had a net improvement averaged over 14 symptoms of +2-4 per cent. A similar result was obtained for the hypertensive patients of +2-0 per cent, the symptoms lost being balanced by those gained. The changes in symptoms with time were related to the changes in blood pressure and it is suggested that only headache, 'unsteadiness, lightheadedness, or faintness' and nocturia can actually result from raised blood pressure and then only in a proportion of patients complaining of these symptoms."} {"id": "PMID:1259822", "title": "[Morphological study of the myocardium in children and adults under normal conditions and in hypoxia].", "content": "At the light and electronic microscopes, 32 myocardial biopsies from 16 patients were studied. The study was carried out in 8 children under 5 years of age and in 8 adults over 20 years during open-sky surgery of the chest done to correct some congenital or acquired heart anomaly. Control biopsies were taken before the application of extracorporeal circulation and a second biopsy, after an average of 30 minutes of hypoxia, which was the time taken to perform the surgical correction of the anomaly. Following extracorporeal circulation, all cases showed mitochondrial mutuations, such as disorganization of their crests, marked distension, from edema to emptiness due to hypoxia. The lack of glycogen, the disorganization of the myofibrillae, decreased neatness of the sarcoplasm and nuclei with marginated chromation, were all preceded by mitochondrial mutations due to oxidative phosphorylation deficiency.", "contents": "[Morphological study of the myocardium in children and adults under normal conditions and in hypoxia]. At the light and electronic microscopes, 32 myocardial biopsies from 16 patients were studied. The study was carried out in 8 children under 5 years of age and in 8 adults over 20 years during open-sky surgery of the chest done to correct some congenital or acquired heart anomaly. Control biopsies were taken before the application of extracorporeal circulation and a second biopsy, after an average of 30 minutes of hypoxia, which was the time taken to perform the surgical correction of the anomaly. Following extracorporeal circulation, all cases showed mitochondrial mutuations, such as disorganization of their crests, marked distension, from edema to emptiness due to hypoxia. The lack of glycogen, the disorganization of the myofibrillae, decreased neatness of the sarcoplasm and nuclei with marginated chromation, were all preceded by mitochondrial mutations due to oxidative phosphorylation deficiency."} {"id": "PMID:1259827", "title": "Echocardiographic evaluation of propranolol therapy for mitral valve prolapse.", "content": "This study evaluates the effect of propranolol on the echocardiogram of 8 patients with late systolic mitral value prolapse. Echocardiograms were performed with the patients on no medication and again while on oral propranolol therapy. Propranolol caused a statistically significant increase in left ventricular volume; however, neither the echocardiographic pattern nor the timing of mitral valve prolapse was altered by propranolol. These findings suggest that factors in addition to left ventricular volume play a role in regulating valvular dysfunction in this condition.", "contents": "Echocardiographic evaluation of propranolol therapy for mitral valve prolapse. This study evaluates the effect of propranolol on the echocardiogram of 8 patients with late systolic mitral value prolapse. Echocardiograms were performed with the patients on no medication and again while on oral propranolol therapy. Propranolol caused a statistically significant increase in left ventricular volume; however, neither the echocardiographic pattern nor the timing of mitral valve prolapse was altered by propranolol. These findings suggest that factors in addition to left ventricular volume play a role in regulating valvular dysfunction in this condition."} {"id": "PMID:1259821", "title": "[Acute leukemia with cardiac infiltration].", "content": "A nine years old female child with malnutrition who showed, six months before admission, a number of clinical manifestations consistent with leukemia. The outstanding clinical manifestation during her hospital stay was that of pericarditis with effusion, which was found associated with pericardial leukemic infiltration. The final picture was that of cardiorespiratory failure associated, both to leukemic infiltration of these organs, as to that of postoperative hemorrhage.", "contents": "[Acute leukemia with cardiac infiltration]. A nine years old female child with malnutrition who showed, six months before admission, a number of clinical manifestations consistent with leukemia. The outstanding clinical manifestation during her hospital stay was that of pericarditis with effusion, which was found associated with pericardial leukemic infiltration. The final picture was that of cardiorespiratory failure associated, both to leukemic infiltration of these organs, as to that of postoperative hemorrhage."} {"id": "PMID:1259823", "title": "[Tetanus in the newborn. Epidemiologic, clinical and therapeutic aspects. Report of 34 cases].", "content": "This study is based on a review of the present situation of tetanus neonatorum. This study included 34 cases which were diagnosed as tetanus of the newborn. These 34 cases occurred in Dr A. Pumarejo hospital in the city of H. Matamoros, Tamaulipas (Mexico), during the period 1970-1974. It was found that during this pediatric age, in comparison with others, the incidence is high (61.8%) and shows a predominance of males over females of 4.62 to 1. The incidence of this pathology, as Cole & Youngman proposed, was as follows: grade I, 2.94% grade II, 11.76%; and 85.30% corresponding to grade III. The greater number of deaths were in those patients classified as grade III, which corresponded to 12 patients. The number of cases studied during spring and summer was much higher. The living conditions within our environment, our ecology and the unawareness of the basic means to prevent this pathology (correct management of the umbilical cord) were the main causes of this high incidence. Therefore, this case study leads to the conclusion that there is a great need to reorganize our programs of vaccination in order to protect this pediatric group, which is highly exposed.", "contents": "[Tetanus in the newborn. Epidemiologic, clinical and therapeutic aspects. Report of 34 cases]. This study is based on a review of the present situation of tetanus neonatorum. This study included 34 cases which were diagnosed as tetanus of the newborn. These 34 cases occurred in Dr A. Pumarejo hospital in the city of H. Matamoros, Tamaulipas (Mexico), during the period 1970-1974. It was found that during this pediatric age, in comparison with others, the incidence is high (61.8%) and shows a predominance of males over females of 4.62 to 1. The incidence of this pathology, as Cole & Youngman proposed, was as follows: grade I, 2.94% grade II, 11.76%; and 85.30% corresponding to grade III. The greater number of deaths were in those patients classified as grade III, which corresponded to 12 patients. The number of cases studied during spring and summer was much higher. The living conditions within our environment, our ecology and the unawareness of the basic means to prevent this pathology (correct management of the umbilical cord) were the main causes of this high incidence. Therefore, this case study leads to the conclusion that there is a great need to reorganize our programs of vaccination in order to protect this pediatric group, which is highly exposed."} {"id": "PMID:1259828", "title": "Opening snap and isovolumic relaxation period in relation to mitral valve flow in patients with mitral stenosis. Significance of A2--OS interval.", "content": "In 15 patients with pure or predominant mitral stenosis and in a control group of 11 patients without mitral stenosis the blood flow velocity through the mitral valve orifice was recorded by means of a directional Doppler ultrasound velocity catheter introduced transeptally and positioned in the orifice of the mitral valve. A simultaneous surface phonocardiogram was obtained. The timing of the mitral opening snap in relation to the blood velocity record of the flow through the valve supported the hypothesis that the opening snap is due to a sudden tensing of the valve leaflets by the chordae tendineae. Determination of the exact time of mitral valve opening, made possible by the blood velocity record, led to the division of the classical A2-0S interval (aortic valve closure to opening snap) into two components representing respectively the diastolic isovolumic relaxation period and the time of excursion of the mitral valve cusps. The durations of the isovolumic relaxation period were compared with those in the control patients and were found to correlate with the severity of the mitral stenosis, whereas those of the excursion time of the mitral cusps were influenced by the presence or absence of mitral valve calcification.", "contents": "Opening snap and isovolumic relaxation period in relation to mitral valve flow in patients with mitral stenosis. Significance of A2--OS interval. In 15 patients with pure or predominant mitral stenosis and in a control group of 11 patients without mitral stenosis the blood flow velocity through the mitral valve orifice was recorded by means of a directional Doppler ultrasound velocity catheter introduced transeptally and positioned in the orifice of the mitral valve. A simultaneous surface phonocardiogram was obtained. The timing of the mitral opening snap in relation to the blood velocity record of the flow through the valve supported the hypothesis that the opening snap is due to a sudden tensing of the valve leaflets by the chordae tendineae. Determination of the exact time of mitral valve opening, made possible by the blood velocity record, led to the division of the classical A2-0S interval (aortic valve closure to opening snap) into two components representing respectively the diastolic isovolumic relaxation period and the time of excursion of the mitral valve cusps. The durations of the isovolumic relaxation period were compared with those in the control patients and were found to correlate with the severity of the mitral stenosis, whereas those of the excursion time of the mitral cusps were influenced by the presence or absence of mitral valve calcification."} {"id": "PMID:1259824", "title": "[Susceptibility of 609 strains of Staphylococcus aureus, isolated during 1973-1974 from various infectious processes in children, to various antibiotics].", "content": "Staphylococcus aureus is a bacterium which has shown variations, as to susceptibility, to antimicrobial agents. By the plate dilution method, response to 12 different antibiotics is studied in 609 strains isolated from children admitted, or who attended the outpatient clinic of the Hospital Infantil de M\u00e9xico, between 1973 and 1974. Ninety per cent or over, of all strains, were sensitive to eight of the antibiotics. The most effective were: gentamicin, (99.8%), cephalothin and cloxacillin (99%). Lesser sensitivity was found to penicillin (28.7%), ampicillin (33.5%) and tetracycline (49%). In general, resistance was greater in cases of surgical wounds and abscesses, and lesser in respiratory infections (pharyngeal exudates and bronchoaspirations). All strains isolated from purulent ophthalmias showed resistance to penicillin and 91%, to ampicillin.", "contents": "[Susceptibility of 609 strains of Staphylococcus aureus, isolated during 1973-1974 from various infectious processes in children, to various antibiotics]. Staphylococcus aureus is a bacterium which has shown variations, as to susceptibility, to antimicrobial agents. By the plate dilution method, response to 12 different antibiotics is studied in 609 strains isolated from children admitted, or who attended the outpatient clinic of the Hospital Infantil de M\u00e9xico, between 1973 and 1974. Ninety per cent or over, of all strains, were sensitive to eight of the antibiotics. The most effective were: gentamicin, (99.8%), cephalothin and cloxacillin (99%). Lesser sensitivity was found to penicillin (28.7%), ampicillin (33.5%) and tetracycline (49%). In general, resistance was greater in cases of surgical wounds and abscesses, and lesser in respiratory infections (pharyngeal exudates and bronchoaspirations). All strains isolated from purulent ophthalmias showed resistance to penicillin and 91%, to ampicillin."} {"id": "PMID:1259829", "title": "Cardiac arrhythmias induced by hypokalaemia and potassium loss during maintenance digoxin therapy.", "content": "Twelve patients with congestive heart failure receiving maintenance therapy with digoxin and potent diuretics were followed closely during development of hypokalemia and potassium loss. Cardiac arrhythmias compatible with digoxtin toxicity developed in 6 patients in the presence of stable, normal serum digoxin concentrations. The mechanisms involved in the development of the rhythm disturbances are discussed with regard to hypokalaemia, intracellular potassium loss, intra-/extracellular potassium gradients and digoxin, and the significance of maintaining a normal potassium balance in this setting is stressed.", "contents": "Cardiac arrhythmias induced by hypokalaemia and potassium loss during maintenance digoxin therapy. Twelve patients with congestive heart failure receiving maintenance therapy with digoxin and potent diuretics were followed closely during development of hypokalemia and potassium loss. Cardiac arrhythmias compatible with digoxtin toxicity developed in 6 patients in the presence of stable, normal serum digoxin concentrations. The mechanisms involved in the development of the rhythm disturbances are discussed with regard to hypokalaemia, intracellular potassium loss, intra-/extracellular potassium gradients and digoxin, and the significance of maintaining a normal potassium balance in this setting is stressed."} {"id": "PMID:1259830", "title": "Intermittent bundle-branch block in patients with accessory atrio-His or atrio-AV nodal pathways. Variants of the Lown-Ganong-Levine syndrome.", "content": "Intracardiac electrophysiological studies were performed in two patients with a documented history of repetitive supraventricular tachyarrhythmias. Case 1, with short PR interval and narrow QRS complexes had a short AH interval and intermittent right bundle-branch block. Thus the short PR wide QRS syndrome is not always a result of the Wolff-Parkinson-White syndrome but can also be seen in the Lown-Ganong-Levine syndrome coexisting with bundle-branch block. Case 2, with normal PR and AH at the lower limits of normal, showed the dual pathway response to atrial pacing that can occur in patients with Lown-Ganong-Levine syndrome. He also had tachycardia-dependent right bundle-branch block and left posterior hemiblock. Therefore, neither the short PR interval nor the narrow QRS complexes characterized these forms of pre-excitation. The constant features were, from the clinical viewpoint, the occurrence of repetitive supraventricular tachyarrhythmias, and electrophysiologically the abnormal response to atrial stimulation.", "contents": "Intermittent bundle-branch block in patients with accessory atrio-His or atrio-AV nodal pathways. Variants of the Lown-Ganong-Levine syndrome. Intracardiac electrophysiological studies were performed in two patients with a documented history of repetitive supraventricular tachyarrhythmias. Case 1, with short PR interval and narrow QRS complexes had a short AH interval and intermittent right bundle-branch block. Thus the short PR wide QRS syndrome is not always a result of the Wolff-Parkinson-White syndrome but can also be seen in the Lown-Ganong-Levine syndrome coexisting with bundle-branch block. Case 2, with normal PR and AH at the lower limits of normal, showed the dual pathway response to atrial pacing that can occur in patients with Lown-Ganong-Levine syndrome. He also had tachycardia-dependent right bundle-branch block and left posterior hemiblock. Therefore, neither the short PR interval nor the narrow QRS complexes characterized these forms of pre-excitation. The constant features were, from the clinical viewpoint, the occurrence of repetitive supraventricular tachyarrhythmias, and electrophysiologically the abnormal response to atrial stimulation."} {"id": "PMID:1259831", "title": "Length of main left coronary artery in relation to atherosclerosis of its branches. A coronary arteriographic study.", "content": "The relation between the length of the main left coronary artery and the presence of atherosclerosis in its branches or the presence of complete left bundle-branch block was studied by selective coronary arteriography in 43 persons. The length of the main left coronary artery was found to be significantly shorter in patients with coronary atherosclerosis than in subjects without angiographic evidence of coronary artery disease. In patients with electrocardiographic evidence of complete left bundle-branch block, the length of the left main coronary artery was significantly shorter than that in both previous groups. In view of these findings, it is suggested that a short main left coronary artery should be considered as a congenital factor predisposing to the development of coronary artery disease. The possible mechanisms leading to atherosclerosis of the left coronary arterial branches in the presence of a short main trunk are discussed.", "contents": "Length of main left coronary artery in relation to atherosclerosis of its branches. A coronary arteriographic study. The relation between the length of the main left coronary artery and the presence of atherosclerosis in its branches or the presence of complete left bundle-branch block was studied by selective coronary arteriography in 43 persons. The length of the main left coronary artery was found to be significantly shorter in patients with coronary atherosclerosis than in subjects without angiographic evidence of coronary artery disease. In patients with electrocardiographic evidence of complete left bundle-branch block, the length of the left main coronary artery was significantly shorter than that in both previous groups. In view of these findings, it is suggested that a short main left coronary artery should be considered as a congenital factor predisposing to the development of coronary artery disease. The possible mechanisms leading to atherosclerosis of the left coronary arterial branches in the presence of a short main trunk are discussed."} {"id": "PMID:1259832", "title": "Analysis of coronary collaterals in ischaemic heart disease by angiography during pacing induced ischaemia.", "content": "Studies were made using ordinary selective coronary angiography and angiography during ischaemia produced by right atrial pacing, on a series of 41 patients with ischaemic heart disease, to examine the response of the collaterals to the ischaemia stimulus. Regional myocardial perfusion was determined under the same circumstances by measuring regional 133Xenon washout curves. No collaterals were found in 8 patients, none of whom demonstrated collaterals when angiography was repeated during ischaemia. Eleven of the 33 patients with prepacing collaterals (33%) responded to ischaemia with an increase in the collaterals, 16 patients (49%) showed no change, 5 patients (15%) showed a decrease in the collaterals, and one patient exhibited a bidirectional change. Regional myocardial perfusion responses closely paralleled the angiographic changes, yielding suggestive evidence that the collaterals were intimately involved in the enhancement of the flow. Despite different collateral and flow responses to ischaemia, the data on exercise tolerance, left ventricular end-diastolic pressure, ejection fraction, prevalence of left ventricular asynergy, and the topographic relation between synergy and collaterals, were largely similar. The data show that in some patients the collateral circulation reacts to ischaemia by enhancement, but the functional significance of this response is obscure.", "contents": "Analysis of coronary collaterals in ischaemic heart disease by angiography during pacing induced ischaemia. Studies were made using ordinary selective coronary angiography and angiography during ischaemia produced by right atrial pacing, on a series of 41 patients with ischaemic heart disease, to examine the response of the collaterals to the ischaemia stimulus. Regional myocardial perfusion was determined under the same circumstances by measuring regional 133Xenon washout curves. No collaterals were found in 8 patients, none of whom demonstrated collaterals when angiography was repeated during ischaemia. Eleven of the 33 patients with prepacing collaterals (33%) responded to ischaemia with an increase in the collaterals, 16 patients (49%) showed no change, 5 patients (15%) showed a decrease in the collaterals, and one patient exhibited a bidirectional change. Regional myocardial perfusion responses closely paralleled the angiographic changes, yielding suggestive evidence that the collaterals were intimately involved in the enhancement of the flow. Despite different collateral and flow responses to ischaemia, the data on exercise tolerance, left ventricular end-diastolic pressure, ejection fraction, prevalence of left ventricular asynergy, and the topographic relation between synergy and collaterals, were largely similar. The data show that in some patients the collateral circulation reacts to ischaemia by enhancement, but the functional significance of this response is obscure."} {"id": "PMID:1259833", "title": "Wenckebach phenomenon in the exit area from a transvenous pacing electrode.", "content": "An unusual type of exist block from a transvenous pacing electrode was recorded in a 63-year-old man with an acute inferior infarct and cardiogenic shock. The pacemaker artefact to QRS interval increased gradually till there was loss of capture. A gradual change from I:I pacing rhythm to 4:3 and 3:2 Wenckebach cycles was recorded. This was followed by a fixed 2:I pacemaker artefact to QRS block.", "contents": "Wenckebach phenomenon in the exit area from a transvenous pacing electrode. An unusual type of exist block from a transvenous pacing electrode was recorded in a 63-year-old man with an acute inferior infarct and cardiogenic shock. The pacemaker artefact to QRS interval increased gradually till there was loss of capture. A gradual change from I:I pacing rhythm to 4:3 and 3:2 Wenckebach cycles was recorded. This was followed by a fixed 2:I pacemaker artefact to QRS block."} {"id": "PMID:1259834", "title": "Wenckebach phenomenon occurring in the distal conducting system in a young adult.", "content": "This report describes the case of a young man who presented with right bundle-branch block and second degree atrioventricular block; intermittent episodes of Wenckebach periods were recorded. His bundle electrograms demonstrated progressive prolongation of the HV interval followed by block occurring distal to His. This report emphasizes the fact that the Wenckebach phenomenon as a manifestation of the distal conducting system disease can occur in young adults. The observations lend credence to the concept that Len\u00e8gre's disease can occur in young people.", "contents": "Wenckebach phenomenon occurring in the distal conducting system in a young adult. This report describes the case of a young man who presented with right bundle-branch block and second degree atrioventricular block; intermittent episodes of Wenckebach periods were recorded. His bundle electrograms demonstrated progressive prolongation of the HV interval followed by block occurring distal to His. This report emphasizes the fact that the Wenckebach phenomenon as a manifestation of the distal conducting system disease can occur in young adults. The observations lend credence to the concept that Len\u00e8gre's disease can occur in young people."} {"id": "PMID:1259835", "title": "Inhibition of demand pacemakers caused by potentials associated with inspiration.", "content": "A 69-year-old man with a permanent demand pacemaker and a unipolar electrode system had intermittent failure of pacing during deep inspiration. Pacing was not interrupted when the unit was switched to fixed rate mode by an external magnet. Thus, the problem was not caused by a change in electrode position or to a loose connexion. The likely cause was inhibition by non-cardiac potentials, possibly myopotentials associated with respiration.", "contents": "Inhibition of demand pacemakers caused by potentials associated with inspiration. A 69-year-old man with a permanent demand pacemaker and a unipolar electrode system had intermittent failure of pacing during deep inspiration. Pacing was not interrupted when the unit was switched to fixed rate mode by an external magnet. Thus, the problem was not caused by a change in electrode position or to a loose connexion. The likely cause was inhibition by non-cardiac potentials, possibly myopotentials associated with respiration."} {"id": "PMID:1259837", "title": "Creatine kinase MB isoenzyme studies in diagnosis of myocardial infarction.", "content": "Serial measurements of the MB isoenzyme of creatine kinase, total creatine kinase, aspartate mainotransferase, and urea stable lactate dehydrogenase have been made in the serum of a series of 139 patients admitted with a diagnosis of suspected myocardial infarction. Serum MB isoenzyme measurements have also been made on postoperative surgical patients and patients with medical disorders known to have caused raised serum total creatine kinase activity. All these enzymes were abnormal in at least one specimen from all patients with electrocardiographically proved acute myocardial infarction. The magnitude of the MB isoenzyme rise was 2 to 3 times greater than that of any of the other enzymes. The duration of its rise was relatively short. The MB isoenzyme was more specific for myocardial infarction than other enzymes and no increases were found in postoperative patients, except in those after cardiac bypass surgery. The MB isoenzyme seems the most sensitive and specific test for myocardial infarction available, though there are technical problems in its accurate measurement.", "contents": "Creatine kinase MB isoenzyme studies in diagnosis of myocardial infarction. Serial measurements of the MB isoenzyme of creatine kinase, total creatine kinase, aspartate mainotransferase, and urea stable lactate dehydrogenase have been made in the serum of a series of 139 patients admitted with a diagnosis of suspected myocardial infarction. Serum MB isoenzyme measurements have also been made on postoperative surgical patients and patients with medical disorders known to have caused raised serum total creatine kinase activity. All these enzymes were abnormal in at least one specimen from all patients with electrocardiographically proved acute myocardial infarction. The magnitude of the MB isoenzyme rise was 2 to 3 times greater than that of any of the other enzymes. The duration of its rise was relatively short. The MB isoenzyme was more specific for myocardial infarction than other enzymes and no increases were found in postoperative patients, except in those after cardiac bypass surgery. The MB isoenzyme seems the most sensitive and specific test for myocardial infarction available, though there are technical problems in its accurate measurement."} {"id": "PMID:1259838", "title": "Correlation between praecordial accelerocardiogram and left ventricular pressure.", "content": "The praecordial accelerocardiogram possesses important practical advantages over more familiar techniques of recording praecordial pulsations. We have compared the amplitude of the P wave of the praecordial accelerocardiogram in 6 normal subjects (group 1) and 21 patients with heart disease (group 2) at rest and after 3 minutes of isometric handgrip at 30 per cent maximum voluntary contraction. At rest in group 2 there was a significant linear correlation between the amplitude of the P wave of the accelerocardiogram, relative to the maximum systolic amplitude (P/DE), and the left ventricular end-diastolic pressure (P less than 0-01). However, comparison of the data for P/DE showed that the mean value (+/-SEM) of 29+/-5 per cent in group 1 was not significantly different from the mean value of 37+/-4 per cent in group 2 (P g .reater than 0-30). During handgrip the mean amplitude of the P wave did not increase significantly in group 1 (P greater than 0-20) but increased significantly in group 2 (P less than 0-02). In group 2 there was a significant linear correlation between the percentage increase in the amplitude of the P wave of the accelerocardiogram during handgrip and the percentage increase in the left ventricular end-diastolic pressure (P less than 0-01).", "contents": "Correlation between praecordial accelerocardiogram and left ventricular pressure. The praecordial accelerocardiogram possesses important practical advantages over more familiar techniques of recording praecordial pulsations. We have compared the amplitude of the P wave of the praecordial accelerocardiogram in 6 normal subjects (group 1) and 21 patients with heart disease (group 2) at rest and after 3 minutes of isometric handgrip at 30 per cent maximum voluntary contraction. At rest in group 2 there was a significant linear correlation between the amplitude of the P wave of the accelerocardiogram, relative to the maximum systolic amplitude (P/DE), and the left ventricular end-diastolic pressure (P less than 0-01). However, comparison of the data for P/DE showed that the mean value (+/-SEM) of 29+/-5 per cent in group 1 was not significantly different from the mean value of 37+/-4 per cent in group 2 (P g .reater than 0-30). During handgrip the mean amplitude of the P wave did not increase significantly in group 1 (P greater than 0-20) but increased significantly in group 2 (P less than 0-02). In group 2 there was a significant linear correlation between the percentage increase in the amplitude of the P wave of the accelerocardiogram during handgrip and the percentage increase in the left ventricular end-diastolic pressure (P less than 0-01)."} {"id": "PMID:1259839", "title": "Clinical features and investigative findings in presence of mitral leaflet prolapse. Study of 85 consecutive patients.", "content": "In a 14-month period mitral leaflet prolapse was diagnosed in 85 patients by echocardiography or cineangiography. Chest pain alone was the presenting complaint in 30 patients and linked with palpitation, dyspnoea, or syncope in 9. Eleven presented with major neurological disturbances (9 had transient ischaemic attacks), 10 with palpitation, 4 with undue and persistent fatigue, 2 with dyspnoea, and 2 with dizziness. Seventeen were referred not because of symptoms but because of clicks and murmurs. Overall, chest pain affected 61 patients and unless associated with coronary artery disease was not anginal. Palpitation was admitted by 42 patients; dizziness, lightheadedness, or paraesthesiae by 15, and syncope by 12. Systolic auscultatory abnormalities were noted in 69: 25 had single clicks, 3 had multiple clicks, 19 had both click(s) and murmur, and 22 had a murmur alone. Electrocardiography revealed ST segments flat for greater than 0-10 s in 21, prolonged QTc in 18, and T wave flattening or inversion in inferior limb and lateral chest leads in 14. The exercise stress test was abnormal in 13 of 27 patients. Mitral valve echograms showed definite mitral leaflet prolapse in 61, 'possible' prolapse in 14, and were normal in 8 patients with angiographic proof of mitral leaflet prolapse. Cardiac catheterization with left ventriculography showed prolapse of posterior mitral leaflet in 36, of both leaflets in 2, and left ventricular wall motion abnormalities in 16 cases. Selective coronary arteriography in 31 cases showed major vessel narrowing of larger than or equal to 80 per cent lumen diameter in 4, all with angina. This consecutive series indicates that the physical event of mitral leaflet prolapse is more common than hitherto appreciated, is priminently associated with non-anginal chest pain, palpitation, and neurological disturbances, and in 90 per cent of cases could be shown echocardiographically.", "contents": "Clinical features and investigative findings in presence of mitral leaflet prolapse. Study of 85 consecutive patients. In a 14-month period mitral leaflet prolapse was diagnosed in 85 patients by echocardiography or cineangiography. Chest pain alone was the presenting complaint in 30 patients and linked with palpitation, dyspnoea, or syncope in 9. Eleven presented with major neurological disturbances (9 had transient ischaemic attacks), 10 with palpitation, 4 with undue and persistent fatigue, 2 with dyspnoea, and 2 with dizziness. Seventeen were referred not because of symptoms but because of clicks and murmurs. Overall, chest pain affected 61 patients and unless associated with coronary artery disease was not anginal. Palpitation was admitted by 42 patients; dizziness, lightheadedness, or paraesthesiae by 15, and syncope by 12. Systolic auscultatory abnormalities were noted in 69: 25 had single clicks, 3 had multiple clicks, 19 had both click(s) and murmur, and 22 had a murmur alone. Electrocardiography revealed ST segments flat for greater than 0-10 s in 21, prolonged QTc in 18, and T wave flattening or inversion in inferior limb and lateral chest leads in 14. The exercise stress test was abnormal in 13 of 27 patients. Mitral valve echograms showed definite mitral leaflet prolapse in 61, 'possible' prolapse in 14, and were normal in 8 patients with angiographic proof of mitral leaflet prolapse. Cardiac catheterization with left ventriculography showed prolapse of posterior mitral leaflet in 36, of both leaflets in 2, and left ventricular wall motion abnormalities in 16 cases. Selective coronary arteriography in 31 cases showed major vessel narrowing of larger than or equal to 80 per cent lumen diameter in 4, all with angina. This consecutive series indicates that the physical event of mitral leaflet prolapse is more common than hitherto appreciated, is priminently associated with non-anginal chest pain, palpitation, and neurological disturbances, and in 90 per cent of cases could be shown echocardiographically."} {"id": "PMID:1259840", "title": "Unstable angina pectoris. Clinical, angiographic, and myocardial scintigraphic observations.", "content": "The clinical, left ventricular and coronary angiographic data, and the technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial scintigraphic results are presented in 31 patients with unstable angina pectoris. One-third of these patients had positive 99mTc-PYP myocardial scintigrams in a pattern suggesting limited and diffuse subendocardial necrosis. The positive 99mTc-PYP myocardial scintigrams occurred without diagnostic electrocardiographic and cardiac enzyme changes suggestive of myocardial infarction; positive scintigrams seemed to occur more commonly in patients with continuing pain after admission and in those without previous history of myocardial infarction. The positive 99mTc-PYP myocardial scintigrams did not correctly predict coronary anatomical patterns except that positive scintigrams occurred only in patients with coronary artery disease. Neither did the positive scintigrams necessarily occur in that group of patients with the poorest ventricular function though the 2 patients with the lowest ejection fractions both had positive 99mTc-PYP myocardial scintigrams. Finally, when positive 99mTc-PYP scintigrams are the only evidence suggestive of limited subendocardial infarction in patients with unstable angina pectoris, they do not appear to have any prognostic significance in terms of longevity or response to pharmacological or surgical therapy, though the follow-up period so far is short.", "contents": "Unstable angina pectoris. Clinical, angiographic, and myocardial scintigraphic observations. The clinical, left ventricular and coronary angiographic data, and the technetium-99m stannous pyrophosphate (99mTc-PYP) myocardial scintigraphic results are presented in 31 patients with unstable angina pectoris. One-third of these patients had positive 99mTc-PYP myocardial scintigrams in a pattern suggesting limited and diffuse subendocardial necrosis. The positive 99mTc-PYP myocardial scintigrams occurred without diagnostic electrocardiographic and cardiac enzyme changes suggestive of myocardial infarction; positive scintigrams seemed to occur more commonly in patients with continuing pain after admission and in those without previous history of myocardial infarction. The positive 99mTc-PYP myocardial scintigrams did not correctly predict coronary anatomical patterns except that positive scintigrams occurred only in patients with coronary artery disease. Neither did the positive scintigrams necessarily occur in that group of patients with the poorest ventricular function though the 2 patients with the lowest ejection fractions both had positive 99mTc-PYP myocardial scintigrams. Finally, when positive 99mTc-PYP scintigrams are the only evidence suggestive of limited subendocardial infarction in patients with unstable angina pectoris, they do not appear to have any prognostic significance in terms of longevity or response to pharmacological or surgical therapy, though the follow-up period so far is short."} {"id": "PMID:1259841", "title": "Echoventriculography in acute myocardial infarction. II: Monitoring of left ventricular performance.", "content": "In acute myocardial infarction the overall left ventricular pump function and the regional performance of the infarcted and non-infarcted myocardial segments were studied serially by echocardiographic techniques in 24 patients during the first week of their illness. Left ventricular cavity sizes were acutely increased in 62 per cent of the patients (P less than 0-005). The end-systolic diameter in anterior infarcts increased to the greatest extent, +44 per cent, the end-diastolic diameter by +27 per cent, giving a volume of 246+/-25 ml. In the anterior myocardial infarcts all the function parameters deteriorated more than in the posteroinferior ones. Ejection fraction was subnormal (P less than 0-005) in every patient, and mean circumferential fibre shortening (Vcf) was slowed by about 30 per cent (P less than 0-005). Regionally, contraction of the infarcted area of the ventricle was asynergic in every instance, and its function was almost totally lost (P less than 0-001). Systolic paradoxical motion was a constant and stable finding in the anterior infarctions but not so in the posterior ones. While this asynergic systolic contraction may distort echocardiographic measurement of the end-systolic left vlic phase. The serial deviations from normal in the amplitude or velocity of the uninvolved segments were small, but in the case of clearly enlarged end-diastolic volumes these figures in fact indicate supernormal, compensating function. Both overall and regional performance were worst within the first 3 days of infarction, improving thereafter. The patient with a fatal course showed, instead, progressive deterioration. This noninvasive left ventriculogram by ultrasound gives valuable insight into overall pump function and ventricular volumes, little studied so far in acute infarction, and it may serially quantify the segmental function of both the infarcted and uninvolved regions.", "contents": "Echoventriculography in acute myocardial infarction. II: Monitoring of left ventricular performance. In acute myocardial infarction the overall left ventricular pump function and the regional performance of the infarcted and non-infarcted myocardial segments were studied serially by echocardiographic techniques in 24 patients during the first week of their illness. Left ventricular cavity sizes were acutely increased in 62 per cent of the patients (P less than 0-005). The end-systolic diameter in anterior infarcts increased to the greatest extent, +44 per cent, the end-diastolic diameter by +27 per cent, giving a volume of 246+/-25 ml. In the anterior myocardial infarcts all the function parameters deteriorated more than in the posteroinferior ones. Ejection fraction was subnormal (P less than 0-005) in every patient, and mean circumferential fibre shortening (Vcf) was slowed by about 30 per cent (P less than 0-005). Regionally, contraction of the infarcted area of the ventricle was asynergic in every instance, and its function was almost totally lost (P less than 0-001). Systolic paradoxical motion was a constant and stable finding in the anterior infarctions but not so in the posterior ones. While this asynergic systolic contraction may distort echocardiographic measurement of the end-systolic left vlic phase. The serial deviations from normal in the amplitude or velocity of the uninvolved segments were small, but in the case of clearly enlarged end-diastolic volumes these figures in fact indicate supernormal, compensating function. Both overall and regional performance were worst within the first 3 days of infarction, improving thereafter. The patient with a fatal course showed, instead, progressive deterioration. This noninvasive left ventriculogram by ultrasound gives valuable insight into overall pump function and ventricular volumes, little studied so far in acute infarction, and it may serially quantify the segmental function of both the infarcted and uninvolved regions."} {"id": "PMID:1259842", "title": "Duration of diastole versus cycle length as correlates of left ventricular ejection time.", "content": "Studies were done on 82 normal subjects to evaluate cycle length versus duration of diastole as determinants of left ventricular ejection time. Cycle length and its reciprocal, heart rate, had the highest correlation with left ventricular ejection time. Removal of the self-correlation of left ventricular ejection time within cycle length reduces the correlation so that, of all intervals, duration of diastole had the highest correlation as a determinant of left ventricular ejection time. Cycle length and heart rate remain valuable as spuriously close but not misleading correlates for predicting or correcting left ventricular ejection time.", "contents": "Duration of diastole versus cycle length as correlates of left ventricular ejection time. Studies were done on 82 normal subjects to evaluate cycle length versus duration of diastole as determinants of left ventricular ejection time. Cycle length and its reciprocal, heart rate, had the highest correlation with left ventricular ejection time. Removal of the self-correlation of left ventricular ejection time within cycle length reduces the correlation so that, of all intervals, duration of diastole had the highest correlation as a determinant of left ventricular ejection time. Cycle length and heart rate remain valuable as spuriously close but not misleading correlates for predicting or correcting left ventricular ejection time."} {"id": "PMID:1259843", "title": "Design of exercise test, with special reference to heart patients.", "content": "Estimation of exercise tolerance in patients with heart disease and significant symptoms can usually not be expressed in terms of maximal oxygen uptake or power at a fixed heart rate calculated from a 'steady state' exercise test. The exercise tolerance can be expressed only by the maximal power developed, when limited by symptoms. For this purpose the level of tolerance is better assessed by a test with small increments and short duration of each work load. In clinical practice this type of almost continuous increase in load was found to be particularly useful in patients with ischaemic heart disease. Comparative studies showed that the work per heart beat at equal loads is significantly higher in the test with continuous increase in load than in the test with steps of 6 minutes duration, both in normal subjects and in heart patients. The difference, however, is small (7%) and for practical purposes these tests have equal validity as a measure of the circulatory capacity.", "contents": "Design of exercise test, with special reference to heart patients. Estimation of exercise tolerance in patients with heart disease and significant symptoms can usually not be expressed in terms of maximal oxygen uptake or power at a fixed heart rate calculated from a 'steady state' exercise test. The exercise tolerance can be expressed only by the maximal power developed, when limited by symptoms. For this purpose the level of tolerance is better assessed by a test with small increments and short duration of each work load. In clinical practice this type of almost continuous increase in load was found to be particularly useful in patients with ischaemic heart disease. Comparative studies showed that the work per heart beat at equal loads is significantly higher in the test with continuous increase in load than in the test with steps of 6 minutes duration, both in normal subjects and in heart patients. The difference, however, is small (7%) and for practical purposes these tests have equal validity as a measure of the circulatory capacity."} {"id": "PMID:1259844", "title": "Biloculate false aneurysm of the right ventricle after cardiac surgery.", "content": "A case of a 12-year-old boy who had double false aneurysms of the right ventricle after incomplete closed pulmonary valvotomy six years earlier is presented. The aneurysms were successfully treated surgically, and the aetiology is discussed.", "contents": "Biloculate false aneurysm of the right ventricle after cardiac surgery. A case of a 12-year-old boy who had double false aneurysms of the right ventricle after incomplete closed pulmonary valvotomy six years earlier is presented. The aneurysms were successfully treated surgically, and the aetiology is discussed."} {"id": "PMID:1259845", "title": "Retrograde His bundle deflection in bundle-branch re-entry.", "content": "Atrial echo beats resulting from a reciprocating mechanism involving the bundle-branches were produced by premature atrial impulses in a patient with an A-V nodal bypass tract. The mechanism of the arrhythmia was suggested by the presence of a retrograde His bundle deflection which appeared 'sandwiched' in between a QRS complex with complete right bundle-branch morphology and a negative P wave. Though at a shorter cycle length the His bundle was still activated retrogradely echo beats were not seen because the retrograde H deflection occurred too early, when both bypass tract and A-V node were still effectively refractory. At the faster driven rate concealed retrograde activation of the right branch (by the premature impulse) was responsible for the right bundle-branch block patterns shown by the post-premature driven beat.", "contents": "Retrograde His bundle deflection in bundle-branch re-entry. Atrial echo beats resulting from a reciprocating mechanism involving the bundle-branches were produced by premature atrial impulses in a patient with an A-V nodal bypass tract. The mechanism of the arrhythmia was suggested by the presence of a retrograde His bundle deflection which appeared 'sandwiched' in between a QRS complex with complete right bundle-branch morphology and a negative P wave. Though at a shorter cycle length the His bundle was still activated retrogradely echo beats were not seen because the retrograde H deflection occurred too early, when both bypass tract and A-V node were still effectively refractory. At the faster driven rate concealed retrograde activation of the right branch (by the premature impulse) was responsible for the right bundle-branch block patterns shown by the post-premature driven beat."} {"id": "PMID:1259846", "title": "Diagnosis and successful surgical treatment of chronic constrictive uraemic pericarditis.", "content": "A case of chronic constrictive uraemic pericarditis successfully treated by pericardectomy is reported together with the pre- and postoperative haemodynamic data.", "contents": "Diagnosis and successful surgical treatment of chronic constrictive uraemic pericarditis. A case of chronic constrictive uraemic pericarditis successfully treated by pericardectomy is reported together with the pre- and postoperative haemodynamic data."} {"id": "PMID:1259847", "title": "Hydatid disease of the heart.", "content": "A case of hydatid cyst of the heart is described, in which the diagnosis was made at coronary angiography; a new angiographic sign is described.", "contents": "Hydatid disease of the heart. A case of hydatid cyst of the heart is described, in which the diagnosis was made at coronary angiography; a new angiographic sign is described."} {"id": "PMID:1259882", "title": "Effect of lithium and rubidium on the sleeping time caused by various intravenous anaesthetics in the mouse.", "content": "The effects of acute and long-term lithium (LiCl) and rubidium chloride (RbCl) treatments on the sleeping time caused by intravenous thipentone, methohexitone, ketamine, propanidid. Althesin and diazepam were studied in white mice. The doses of the anasthetic agents were selected from the dose-response experiments. When given acutely, LiCl 5 m-equiv/kg prolonged significantly the sleeping time caused by both of the barbiturates, whereas RbCl given for 21 days in tap water shortened the sleeping time induced by methohexitone and ketamine. Both LiCl and RbCl, given acutely, enhanced the sleeping time caused by diazepam. The rectal temperatures were lower in the LiCl-treated mice than in the control and RbCl-treated mice.", "contents": "Effect of lithium and rubidium on the sleeping time caused by various intravenous anaesthetics in the mouse. The effects of acute and long-term lithium (LiCl) and rubidium chloride (RbCl) treatments on the sleeping time caused by intravenous thipentone, methohexitone, ketamine, propanidid. Althesin and diazepam were studied in white mice. The doses of the anasthetic agents were selected from the dose-response experiments. When given acutely, LiCl 5 m-equiv/kg prolonged significantly the sleeping time caused by both of the barbiturates, whereas RbCl given for 21 days in tap water shortened the sleeping time induced by methohexitone and ketamine. Both LiCl and RbCl, given acutely, enhanced the sleeping time caused by diazepam. The rectal temperatures were lower in the LiCl-treated mice than in the control and RbCl-treated mice."} {"id": "PMID:1259883", "title": "The effect of methoxyflurane on pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in the isolated perfused cat lung.", "content": "The effects of methoxyflurane on pulmonary vascular resistance and the pulmonary vasoconstrictor response to alveolar hypoxia were studied in isolated cat lungs perfused at a constant flow. Methoxyflurane decreased pulmonary vascular resistance and depressed the pulmonary vasoconstrictor response to hypoxia.", "contents": "The effect of methoxyflurane on pulmonary vascular resistance and hypoxic pulmonary vasoconstriction in the isolated perfused cat lung. The effects of methoxyflurane on pulmonary vascular resistance and the pulmonary vasoconstrictor response to alveolar hypoxia were studied in isolated cat lungs perfused at a constant flow. Methoxyflurane decreased pulmonary vascular resistance and depressed the pulmonary vasoconstrictor response to hypoxia."} {"id": "PMID:1259884", "title": "Errors in oxygen tension measurements caused by halothane.", "content": "Halothane, independent of oxygen tension, increased the signal of the gold/silver-silver chloride microelectrode. The output of microelectrodes at different oxygen tensions in the presence of increasing amounts of halothane has been measured. Halothane causes an increase in the electrode signal which is proportional to its concentration. This effect results from the polarographic reduction of halothane. It is concluded that the gold/silver-silver chloride microelectrode cannot be used to measure oxygen tension during halothane anaesthesia.", "contents": "Errors in oxygen tension measurements caused by halothane. Halothane, independent of oxygen tension, increased the signal of the gold/silver-silver chloride microelectrode. The output of microelectrodes at different oxygen tensions in the presence of increasing amounts of halothane has been measured. Halothane causes an increase in the electrode signal which is proportional to its concentration. This effect results from the polarographic reduction of halothane. It is concluded that the gold/silver-silver chloride microelectrode cannot be used to measure oxygen tension during halothane anaesthesia."} {"id": "PMID:1259885", "title": "Effect of dose and premedication on induction complications with etomidate.", "content": "The induction characteristics of etomidate, a new i.v. hypnotic agent, were studied in 400 patients. Two hundred were premedicated with atropine and anaesthesia was induced with 0.2, 0.25, 0.3 or 0.35 mg/kg of etomidate. The remainder received one of four standard premedications and anaesthesia was induced with etomidate 0.3 mg/kg. Involuntary muscle movements occurred in more than 60% of patients receiving atropine alone. The frequency was reduced in the second group, but remained unacceptable in over 8% of patients. The incidence of other excitatory phenomena, such as cough and hiccup, was 10% approximately. Cardiovascular changes were minimal and no serious allergic phenomena were observed. Nausea and vomiting occurred after surgery in up to 30% of patients and was unrelated to the dose of etomidate or to premedication. Pain on injection occurred in up to 80% of patients when the drug was injected into small peripheral veins and occurred in more than 7% when using more normal veins.", "contents": "Effect of dose and premedication on induction complications with etomidate. The induction characteristics of etomidate, a new i.v. hypnotic agent, were studied in 400 patients. Two hundred were premedicated with atropine and anaesthesia was induced with 0.2, 0.25, 0.3 or 0.35 mg/kg of etomidate. The remainder received one of four standard premedications and anaesthesia was induced with etomidate 0.3 mg/kg. Involuntary muscle movements occurred in more than 60% of patients receiving atropine alone. The frequency was reduced in the second group, but remained unacceptable in over 8% of patients. The incidence of other excitatory phenomena, such as cough and hiccup, was 10% approximately. Cardiovascular changes were minimal and no serious allergic phenomena were observed. Nausea and vomiting occurred after surgery in up to 30% of patients and was unrelated to the dose of etomidate or to premedication. Pain on injection occurred in up to 80% of patients when the drug was injected into small peripheral veins and occurred in more than 7% when using more normal veins."} {"id": "PMID:1259886", "title": "A clinical assessment of the use of etomidate in children.", "content": "Etomidate 0.2 mg/kg i.v. was used to induce sleep in 198 children. It produced sleep rapidly and safely, with negligible effect on the cardiovascular system and little respiratory depression. Clinical acceptability was reduced by a 27% incidence of pain after injection, a 10% incidence of myoclonia and inadequate dosage in 19%. Etomidate has little analgesic activity and these problems can be reduced by the use of an analgesic as premedication or with induction of anaesthesia, by increasing the induction dose of etomidate to 0.3-0.4 mg/kg, or by changing the formulation of the solution.", "contents": "A clinical assessment of the use of etomidate in children. Etomidate 0.2 mg/kg i.v. was used to induce sleep in 198 children. It produced sleep rapidly and safely, with negligible effect on the cardiovascular system and little respiratory depression. Clinical acceptability was reduced by a 27% incidence of pain after injection, a 10% incidence of myoclonia and inadequate dosage in 19%. Etomidate has little analgesic activity and these problems can be reduced by the use of an analgesic as premedication or with induction of anaesthesia, by increasing the induction dose of etomidate to 0.3-0.4 mg/kg, or by changing the formulation of the solution."} {"id": "PMID:1259887", "title": "A dose-response relationship for etomidate, with some observations on cumulation.", "content": "In a within-patient comparison in 30 subjects, sleep was induced before e.c.t. by different doses of etomidate or methohexitone: etomidate 0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg or methohexitone 1.5 mg/kg. The duration of hypnotic effect was assessed by recording the time of spontaneous waking and later, of recovery of normal ocular muscle tone. Doubling the dose of etomidate produced a significant increase in both sleeping time and late recovery. Compared with methohexitone 1.5 mg/kg, etomidate 0.2 mg/kg provides an equal duration of sleep, but allows faster late recovery. In eight patients in whome sleep was maintained by repeated injections of etomidate 0.1 mg/kg as required, little evidence of cumulation was seen up to 27.5 min duration of sleep.", "contents": "A dose-response relationship for etomidate, with some observations on cumulation. In a within-patient comparison in 30 subjects, sleep was induced before e.c.t. by different doses of etomidate or methohexitone: etomidate 0.1 mg/kg, 0.2 mg/kg, 0.4 mg/kg or methohexitone 1.5 mg/kg. The duration of hypnotic effect was assessed by recording the time of spontaneous waking and later, of recovery of normal ocular muscle tone. Doubling the dose of etomidate produced a significant increase in both sleeping time and late recovery. Compared with methohexitone 1.5 mg/kg, etomidate 0.2 mg/kg provides an equal duration of sleep, but allows faster late recovery. In eight patients in whome sleep was maintained by repeated injections of etomidate 0.1 mg/kg as required, little evidence of cumulation was seen up to 27.5 min duration of sleep."} {"id": "PMID:1259888", "title": "Thyroid-pituitary response to cardiopulmonary bypass.", "content": "The effects of open heart surgery on various parameters of thyroid-pituitary function were studied in 11 patients. The pattern of hormonal changes was variable. T4 concentration increased during anaesthesia and bypass, following which it returned to normal once haemodynamic stability had been regained. The pattern of change in T3 concentration did not follow consistently that of T4 and the proportional increase in concentration was not as great. There was a significant reduction in T3 concentration with the onset of haemodynamic stability. For individual patients there was no obvious correlation between changes in the concentrations of TSH, T3 and T4. The increases may be explained by release of T3 or T4 from extrathyroid tissue.", "contents": "Thyroid-pituitary response to cardiopulmonary bypass. The effects of open heart surgery on various parameters of thyroid-pituitary function were studied in 11 patients. The pattern of hormonal changes was variable. T4 concentration increased during anaesthesia and bypass, following which it returned to normal once haemodynamic stability had been regained. The pattern of change in T3 concentration did not follow consistently that of T4 and the proportional increase in concentration was not as great. There was a significant reduction in T3 concentration with the onset of haemodynamic stability. For individual patients there was no obvious correlation between changes in the concentrations of TSH, T3 and T4. The increases may be explained by release of T3 or T4 from extrathyroid tissue."} {"id": "PMID:1259889", "title": "Clearance of indocyanine green as an index of liver function during cyclopropane anaesthesia and induced hypotension.", "content": "The rate of decrease in the plasma concentration of indocyanine green (ICG) following a bolus i.v. injection has been studied in two groups of patients before and during anaesthesia. In eight patients anaesthetized with nitrous oxide and oxygen, and who received a neuromuscular blocking drug, induction of anaesthesia was not associated with a significant change in ICG half-life (from 4.59 to 3.85 min) but the subsequent administration of cyclopropane was associated with a statistically significant increase to 5.61 min. In a second group of anaesthetized patients, breathing spontaneously a mixture of oxygen, nitrous oxide and halothane, the induction of arterial hypotension with either lumbar extradural block or sodium nitroprusside was not associated with significant changes in ICG half-life.", "contents": "Clearance of indocyanine green as an index of liver function during cyclopropane anaesthesia and induced hypotension. The rate of decrease in the plasma concentration of indocyanine green (ICG) following a bolus i.v. injection has been studied in two groups of patients before and during anaesthesia. In eight patients anaesthetized with nitrous oxide and oxygen, and who received a neuromuscular blocking drug, induction of anaesthesia was not associated with a significant change in ICG half-life (from 4.59 to 3.85 min) but the subsequent administration of cyclopropane was associated with a statistically significant increase to 5.61 min. In a second group of anaesthetized patients, breathing spontaneously a mixture of oxygen, nitrous oxide and halothane, the induction of arterial hypotension with either lumbar extradural block or sodium nitroprusside was not associated with significant changes in ICG half-life."} {"id": "PMID:1259890", "title": "Placental transfer of 14C-dimethyltubocurarine during Caesarean section.", "content": "Placental transfer of 14C-dimethyltubocurarine (14C-dmtc) was studied during Caesarean section. Liquid scintillation counting was used for determination of 14C activity from the maternal and foetal blood samples. Paper chromatography was used to confirm the stability of 14C-dmtc. In all cases 14C-dmtc was able to cross the placenta. Detectable amounts of 14C-dmtc were found in umbilical blood 2 min after injection into the mother. Six and 10 min after injection, the 14C concentration in the umbilical blood was 12% of the corresponding maternal value.", "contents": "Placental transfer of 14C-dimethyltubocurarine during Caesarean section. Placental transfer of 14C-dimethyltubocurarine (14C-dmtc) was studied during Caesarean section. Liquid scintillation counting was used for determination of 14C activity from the maternal and foetal blood samples. Paper chromatography was used to confirm the stability of 14C-dmtc. In all cases 14C-dmtc was able to cross the placenta. Detectable amounts of 14C-dmtc were found in umbilical blood 2 min after injection into the mother. Six and 10 min after injection, the 14C concentration in the umbilical blood was 12% of the corresponding maternal value."} {"id": "PMID:1259891", "title": "The effect of thoracic extradural analgesia on pulmonary gas distribution, functional residual capacity and airway closure.", "content": "Pulmonary gas distribution, functional residual capacity (FRC), closing capacity (CC), arterial oxygen tension (PaO2) and alveolar-arterial oxygen tension gradient (PAO2-PAO2) were measured in seven subjects before and after the induction of extradural analgesia for routine surgery. It was found that pulmonary gas distribution was within normal limits throughout the study, although there were two patients in whom airway closure occurred consistently within the tidal volume. In both cases this was associated with a low PaO2. CC and FRC were substantially unchanged by the induction of extradural analgesia. Changes in (PAO2-PaO2) and PaO2 were usually not large, and are apparently related to factors other than changes in lung geometry.", "contents": "The effect of thoracic extradural analgesia on pulmonary gas distribution, functional residual capacity and airway closure. Pulmonary gas distribution, functional residual capacity (FRC), closing capacity (CC), arterial oxygen tension (PaO2) and alveolar-arterial oxygen tension gradient (PAO2-PAO2) were measured in seven subjects before and after the induction of extradural analgesia for routine surgery. It was found that pulmonary gas distribution was within normal limits throughout the study, although there were two patients in whom airway closure occurred consistently within the tidal volume. In both cases this was associated with a low PaO2. CC and FRC were substantially unchanged by the induction of extradural analgesia. Changes in (PAO2-PaO2) and PaO2 were usually not large, and are apparently related to factors other than changes in lung geometry."} {"id": "PMID:1259892", "title": "Ventilatory response to carbon dioxide in patients with homozygous sickle-cell disease.", "content": "The ventilatory response to carbon dioxide was measured by a rebreathing technique in 21 Nigerians who had homozygous sickle-cell disease. The slope of the carbon dioxide response curve was obtained by plotting the ventilation at successive half-minute intervals against the corresponding mean end-tidal PCO2. Our results showed that sickle-cell patients are as sensitive to carbon dioxide as are normal subjects.", "contents": "Ventilatory response to carbon dioxide in patients with homozygous sickle-cell disease. The ventilatory response to carbon dioxide was measured by a rebreathing technique in 21 Nigerians who had homozygous sickle-cell disease. The slope of the carbon dioxide response curve was obtained by plotting the ventilation at successive half-minute intervals against the corresponding mean end-tidal PCO2. Our results showed that sickle-cell patients are as sensitive to carbon dioxide as are normal subjects."} {"id": "PMID:1259893", "title": "Renal failure and postoperative respiratory failure: recurarization?", "content": "The occurrence of acute postoperative respiratory failure in three patients with renal failure is presented. The most likely cause was the return of muscle paralysis after the apparent antagonism of tubocurarine by neostigmine (recurarization). In addition to reducing the dose of tubocurarine, the authors recommend that pyridostigmine be used as an antagonist instead of neostigmine because the former has a longer duration of action.", "contents": "Renal failure and postoperative respiratory failure: recurarization? The occurrence of acute postoperative respiratory failure in three patients with renal failure is presented. The most likely cause was the return of muscle paralysis after the apparent antagonism of tubocurarine by neostigmine (recurarization). In addition to reducing the dose of tubocurarine, the authors recommend that pyridostigmine be used as an antagonist instead of neostigmine because the former has a longer duration of action."} {"id": "PMID:1259913", "title": "Estimation in sera by radioimmunoassay of a specific membrane antigen associated with a murine lymphoma.", "content": "Material with a molecular weight of less than 10(5) daltons has been isolated and partially purified from the ascitic fluid of DBA2 mice bearing a syngeneic lymphoma (SL2). This substance inhibits the cytotoxic action of an allogeneic antiserum directed specifically against SL2 cells. Material has been rendered radioactive with 125I and between 20 and 25% of the radioactivity is bound in a specific manner to the antiserum. The material which is referred to as 125I-TSTA has been used in a radioimmunoassay to measure the level of TSTA in the sera of mice bearing both ascitic and subcutaneous SL2 tumours. The level of circulating TSTA was found to be high immediatley following inoculation of live SL2 cells, probably because a large proportion of the injected cells autolyse. The serum concentration of TSTA then falls but 6-10 days later begins to rise again in parallel with the growth of the SL2 tumour either in the peritoneal cavity or subcutaneously. Following surgical removal of an intradermal SL2 tumour the level of TSTA in the serum falls rapidly. No evidence could be found that a significant proportion of the TSTA in the serum of tumour-bearing mice is completed with antibody. However, in the serum of DBA2 mice which have been hyperimmunized with irradiated SL2 cells there are antibodies which bind 125I-TSTA although syngeneic anti-SL2 sera, unlike alloantisera, do not show complement dependent lysis of SL2 cells.", "contents": "Estimation in sera by radioimmunoassay of a specific membrane antigen associated with a murine lymphoma. Material with a molecular weight of less than 10(5) daltons has been isolated and partially purified from the ascitic fluid of DBA2 mice bearing a syngeneic lymphoma (SL2). This substance inhibits the cytotoxic action of an allogeneic antiserum directed specifically against SL2 cells. Material has been rendered radioactive with 125I and between 20 and 25% of the radioactivity is bound in a specific manner to the antiserum. The material which is referred to as 125I-TSTA has been used in a radioimmunoassay to measure the level of TSTA in the sera of mice bearing both ascitic and subcutaneous SL2 tumours. The level of circulating TSTA was found to be high immediatley following inoculation of live SL2 cells, probably because a large proportion of the injected cells autolyse. The serum concentration of TSTA then falls but 6-10 days later begins to rise again in parallel with the growth of the SL2 tumour either in the peritoneal cavity or subcutaneously. Following surgical removal of an intradermal SL2 tumour the level of TSTA in the serum falls rapidly. No evidence could be found that a significant proportion of the TSTA in the serum of tumour-bearing mice is completed with antibody. However, in the serum of DBA2 mice which have been hyperimmunized with irradiated SL2 cells there are antibodies which bind 125I-TSTA although syngeneic anti-SL2 sera, unlike alloantisera, do not show complement dependent lysis of SL2 cells."} {"id": "PMID:1259914", "title": "The growth patterns of two transplantable acute leukaemias of spontaneous origin in rats.", "content": "The growth pattern and morphology of two transplantable acute leukaemias which arose spontaneously in pure line rats are described. They differ morphologically and on the basis of their behaviour in vivo, such as infiltration of lymphoid organs and presence in thoracic duct lymph, the leukaemia syngeneic to the August strain (referred to as the SAL) appears to be of myeloid type whereas the leukaemia syngeneic to the Hooded strain (referred to as the HRL) resembles acute lymphoblastic leukaemia. The HRL cells, but not the SAL cells, are lysed by murine anti-theta serum plus complement. These two transplantable acute leukaemias appear to be useful animal counterparts ot the human acute leukaemias and may be valuable models for studies on chemotherapy and immunotherapy.", "contents": "The growth patterns of two transplantable acute leukaemias of spontaneous origin in rats. The growth pattern and morphology of two transplantable acute leukaemias which arose spontaneously in pure line rats are described. They differ morphologically and on the basis of their behaviour in vivo, such as infiltration of lymphoid organs and presence in thoracic duct lymph, the leukaemia syngeneic to the August strain (referred to as the SAL) appears to be of myeloid type whereas the leukaemia syngeneic to the Hooded strain (referred to as the HRL) resembles acute lymphoblastic leukaemia. The HRL cells, but not the SAL cells, are lysed by murine anti-theta serum plus complement. These two transplantable acute leukaemias appear to be useful animal counterparts ot the human acute leukaemias and may be valuable models for studies on chemotherapy and immunotherapy."} {"id": "PMID:1259915", "title": "Interference by cortisone with endotoxin's adjuvator action on transplantation of a mouse tumour.", "content": "Observations on the in vivo plating of mouse mammary tumour are extended by making counts of tumours at a significantly earlier phase of development than in previously reported work. In the experiments now described, most of the growth of the tumours has been without benefit of stroma. The noteworthy economy of the experimental method is discussed. The persistence of endotoxin's adjuvator effect on such tumour counts is tested in the face of gamma irradiation and cortisone. Cortisone, it is found, offsets endotoxin's adjuvator action; irradiation does not. Antagonism between endotoxin and cortisone, in this system with tumour cells plated in vivo, seems to indicate that endotoxin's enhancing effect depends more on inflammatory than on immunological factors.", "contents": "Interference by cortisone with endotoxin's adjuvator action on transplantation of a mouse tumour. Observations on the in vivo plating of mouse mammary tumour are extended by making counts of tumours at a significantly earlier phase of development than in previously reported work. In the experiments now described, most of the growth of the tumours has been without benefit of stroma. The noteworthy economy of the experimental method is discussed. The persistence of endotoxin's adjuvator effect on such tumour counts is tested in the face of gamma irradiation and cortisone. Cortisone, it is found, offsets endotoxin's adjuvator action; irradiation does not. Antagonism between endotoxin and cortisone, in this system with tumour cells plated in vivo, seems to indicate that endotoxin's enhancing effect depends more on inflammatory than on immunological factors."} {"id": "PMID:1259916", "title": "Reproductive and endocrine function in patients with Hodgkin's disease: effects of oophoropexy and irradiation.", "content": "Reproductive and endocrine function was investigated in 22 women with Hodgkin's disease who had bilateral mid-line oophoropexies performed at staging laparotomy. The operation was followed in 12 cases by \"inverted Y\" pelvic lymph node irradiation and in 4 cases by para-aortic lymph node irradiation. Pregnancies occurred after the operation in 4 of the 6 patients subsequently found not to require irradiation below the diaphragm. In the other 2 patients in this group the menstrual history was unaffected and normal gonadotrophin concentrations indicated intact ovarian function. In the group receiving para-aortic irradiation, in whom the ovarian irradiation dose was was small (about 150 rad to each ovary) menstrual function and gonadotrophin concentrations were normal at the time of review and one patient has subsequently become pregnant. In the group receiving inverted Y irradiation, in whom the ovaries were shielded from the radiation beam by a rectangular lead block, the ovarian dose was much higher (lowest dose 600 rad, highest dose 3500 rad). Nine of the 12 have persisting amenorrhoea with elevated levels of both gonadotrophins. One patient has since become pregnant and one patient has resumed menstrual cycles and has normal basal gonadotrophin concentrations. One patient who has resumed menstrual cycles has a monotrophic elevation of basal serum FSH concentrations. We conclude that bilateral mid-line oophoropexy does not impair ovarian function or gamete transport and should be performed at diagnositc laparotomy in women of child bearing age with Hodgkin's disease, even when it is uncertain whether pelvic node irradiation will be necessary. The results in the patients who received inverted Y irradiation indicate that the technique of pelvic shielding and ovarian transposition used were only partially successful in preserving fertility. Alternative techniques for preserving ovarian function are discussed.", "contents": "Reproductive and endocrine function in patients with Hodgkin's disease: effects of oophoropexy and irradiation. Reproductive and endocrine function was investigated in 22 women with Hodgkin's disease who had bilateral mid-line oophoropexies performed at staging laparotomy. The operation was followed in 12 cases by \"inverted Y\" pelvic lymph node irradiation and in 4 cases by para-aortic lymph node irradiation. Pregnancies occurred after the operation in 4 of the 6 patients subsequently found not to require irradiation below the diaphragm. In the other 2 patients in this group the menstrual history was unaffected and normal gonadotrophin concentrations indicated intact ovarian function. In the group receiving para-aortic irradiation, in whom the ovarian irradiation dose was was small (about 150 rad to each ovary) menstrual function and gonadotrophin concentrations were normal at the time of review and one patient has subsequently become pregnant. In the group receiving inverted Y irradiation, in whom the ovaries were shielded from the radiation beam by a rectangular lead block, the ovarian dose was much higher (lowest dose 600 rad, highest dose 3500 rad). Nine of the 12 have persisting amenorrhoea with elevated levels of both gonadotrophins. One patient has since become pregnant and one patient has resumed menstrual cycles and has normal basal gonadotrophin concentrations. One patient who has resumed menstrual cycles has a monotrophic elevation of basal serum FSH concentrations. We conclude that bilateral mid-line oophoropexy does not impair ovarian function or gamete transport and should be performed at diagnositc laparotomy in women of child bearing age with Hodgkin's disease, even when it is uncertain whether pelvic node irradiation will be necessary. The results in the patients who received inverted Y irradiation indicate that the technique of pelvic shielding and ovarian transposition used were only partially successful in preserving fertility. Alternative techniques for preserving ovarian function are discussed."} {"id": "PMID:1259918", "title": "Beclomethasone dipropionate aerosol and oropharyngeal candidiasis.", "content": "In a survey of 400 consecutive patients with chronic asthma treated with beclomethasone dipropionate aerosol (up to 400 mug/day) the prevalence of oropharyngeal thrush was 4-5%. The prevalence of this complication was not significantly related to sex, age, duration of treatment with beclomethasone or concurrent treatment with prednisolone. Yeasts were isolated from throat swabs in about 60% of all patients and in 48% of normal controls. Thus, although a diagnosis of oropharyngeal thrush was recorded only when the presence of characteristic lesions in the pharynx was associated with a positive culture, there was a large number of patients and controls without thrush who harboured yeasts in the throat. One in 3 patients with thrush complained of sore throat or hoarseness, but 1 in 4 patients without thrush had similar symptoms. These findings suggest that, although treatment with beclomethasone dipoprionate aerosol undoubtedly can cause oropharyngeal thrush, this condition is not an inevitable result of colonization of the oropharynx by yeasts, nor is it necessarily associated with symptoms.", "contents": "Beclomethasone dipropionate aerosol and oropharyngeal candidiasis. In a survey of 400 consecutive patients with chronic asthma treated with beclomethasone dipropionate aerosol (up to 400 mug/day) the prevalence of oropharyngeal thrush was 4-5%. The prevalence of this complication was not significantly related to sex, age, duration of treatment with beclomethasone or concurrent treatment with prednisolone. Yeasts were isolated from throat swabs in about 60% of all patients and in 48% of normal controls. Thus, although a diagnosis of oropharyngeal thrush was recorded only when the presence of characteristic lesions in the pharynx was associated with a positive culture, there was a large number of patients and controls without thrush who harboured yeasts in the throat. One in 3 patients with thrush complained of sore throat or hoarseness, but 1 in 4 patients without thrush had similar symptoms. These findings suggest that, although treatment with beclomethasone dipoprionate aerosol undoubtedly can cause oropharyngeal thrush, this condition is not an inevitable result of colonization of the oropharynx by yeasts, nor is it necessarily associated with symptoms."} {"id": "PMID:1259919", "title": "Gastrointestinal tuberculosis.", "content": "Gastrointestinal tuberculosis continues to occur sporadically in hospitals in the British Isles. Accurate diagnosis may enable its rare but lethal complications to be anticipated. Pathology, clinical features and treatment are reviewed. The use of antituberculous chemotherapy and corticosteroids is discussed with reference to 14 cases of gastrointestinal tuberculosis seen in Southampton between 1951 and 1973.", "contents": "Gastrointestinal tuberculosis. Gastrointestinal tuberculosis continues to occur sporadically in hospitals in the British Isles. Accurate diagnosis may enable its rare but lethal complications to be anticipated. Pathology, clinical features and treatment are reviewed. The use of antituberculous chemotherapy and corticosteroids is discussed with reference to 14 cases of gastrointestinal tuberculosis seen in Southampton between 1951 and 1973."} {"id": "PMID:1259920", "title": "Increased upper airway resistance in patients with airway narrowing.", "content": "The mean air flow resistance of the orolaryngeal (upper) airway was significantly increased in 7 of 11 patients with chronic airway obstruction, when compared with 6 controls. All the patients had noisy respiration with harsh breath sounds audible by auscultation over the larynx. The increase in resistance was greater during expiration than during inspiration. Since 4 patients had normal upper airway resistance, the signs were not invariably associated with upper airway narrowing and presumably could arise also in the chest. When increased, upper airway resistance was usually more than half the total airway resistance. It is suggested that this increase could only be due to narrowing of the glottis, probably by muscle activity. This narrowing may have had the same function as expiration through pursed lips. On the other hand, when present, the increased resistance through the upper airway during inspiration is unlikely to have had a useful function.", "contents": "Increased upper airway resistance in patients with airway narrowing. The mean air flow resistance of the orolaryngeal (upper) airway was significantly increased in 7 of 11 patients with chronic airway obstruction, when compared with 6 controls. All the patients had noisy respiration with harsh breath sounds audible by auscultation over the larynx. The increase in resistance was greater during expiration than during inspiration. Since 4 patients had normal upper airway resistance, the signs were not invariably associated with upper airway narrowing and presumably could arise also in the chest. When increased, upper airway resistance was usually more than half the total airway resistance. It is suggested that this increase could only be due to narrowing of the glottis, probably by muscle activity. This narrowing may have had the same function as expiration through pursed lips. On the other hand, when present, the increased resistance through the upper airway during inspiration is unlikely to have had a useful function."} {"id": "PMID:1259921", "title": "Hepatic erythropoietin: enhanced production in anephric rats with hyperplasia of Kupffer cells.", "content": "Erythropoietin (Ep) levels were assayed in serum of adult male rats subjected sequentially to (1) administration of colloidal carbon, Zymosan or their vehicles (2) sham operation or bilateral nephrectomy with and without subtotal hepatictomy, and (3) hypoxia (0.45-0.40 atmospheres of air for 6 h starting 1 h after the operation). In anephric rats these agents induced a significant potentiation of hypoxic Ep activity. Since they did not apparently modify the kinetics of exogenous Ep, it is postulated that this phenomenon is mediated by enhanced extrarenal Ep production. Both colloidal carbon and Zymosan induced hyperplasia of the reticuloendothelial system (RES). Moreover, subtotal hepatectomy almost abolished the Ep response to hypoxia evoked by Zymosan. The correlation between hyperplasia of hepatic RES and enhanced Ep production in anephric rats primed with these agents suggests that Kupffer cells constitute a major source for extrarenal Ep. Additionally, it is of interest that colloidal carbon and Zymosan did not significantly modify the renal production of Ep.", "contents": "Hepatic erythropoietin: enhanced production in anephric rats with hyperplasia of Kupffer cells. Erythropoietin (Ep) levels were assayed in serum of adult male rats subjected sequentially to (1) administration of colloidal carbon, Zymosan or their vehicles (2) sham operation or bilateral nephrectomy with and without subtotal hepatictomy, and (3) hypoxia (0.45-0.40 atmospheres of air for 6 h starting 1 h after the operation). In anephric rats these agents induced a significant potentiation of hypoxic Ep activity. Since they did not apparently modify the kinetics of exogenous Ep, it is postulated that this phenomenon is mediated by enhanced extrarenal Ep production. Both colloidal carbon and Zymosan induced hyperplasia of the reticuloendothelial system (RES). Moreover, subtotal hepatectomy almost abolished the Ep response to hypoxia evoked by Zymosan. The correlation between hyperplasia of hepatic RES and enhanced Ep production in anephric rats primed with these agents suggests that Kupffer cells constitute a major source for extrarenal Ep. Additionally, it is of interest that colloidal carbon and Zymosan did not significantly modify the renal production of Ep."} {"id": "PMID:1259922", "title": "In vitro binding of folates by body fluids.", "content": "It is useful to differentiate between saturated folate binders in serum (carrying endogenous folate) and unsaturated binders (investigated in the present study). These two groups of binders need not necessarily be chemically identical and the unsaturated binder may even be an in vitro artifact, especially when measured with non-physiological folates. Macromolecular binding of radio-active N-5-methyl tetrahydrofolic acid (CH3H4PteGlu) and/or folic acid (PteGlu) by human serum and urine was assessed by means of exhaustive saline dialysis, haemoglobin-coated charcoal adsorption, column chromatography with DEAE-Sephadex A-50, and sucrose gradient analysis. Binding was found to be minimal or absent. Charcoal adsorption showed a mean serum binding capacity of 0 mug/1. for PteGlu and 0.58 mug/1. for CH3H4PteGlu. In pregnancy the mean serum values were 0.23 mug/1. for PteGlu, 0.66 mjg/1. for CH3H4PteGlu, and with folate deficiency 0.30 mug/1. for PteGlu, 0.49 mug/1. for CH3H4PteGlu. Mean urinary folate binding was minimal (less than 0.5 mug/1.), and red cell haemolysate similarly revealed very low binding on exhaustive dialysis. Column chromatography showed that tracer doses of [14C]PteGlu added to serum migrated distally to the protein zone; [14C]CH3H4PteGlu similarly showed no evidence of protein binding. On a sucrose gradient [14C]PteGlu also separated clear of the protein zone.", "contents": "In vitro binding of folates by body fluids. It is useful to differentiate between saturated folate binders in serum (carrying endogenous folate) and unsaturated binders (investigated in the present study). These two groups of binders need not necessarily be chemically identical and the unsaturated binder may even be an in vitro artifact, especially when measured with non-physiological folates. Macromolecular binding of radio-active N-5-methyl tetrahydrofolic acid (CH3H4PteGlu) and/or folic acid (PteGlu) by human serum and urine was assessed by means of exhaustive saline dialysis, haemoglobin-coated charcoal adsorption, column chromatography with DEAE-Sephadex A-50, and sucrose gradient analysis. Binding was found to be minimal or absent. Charcoal adsorption showed a mean serum binding capacity of 0 mug/1. for PteGlu and 0.58 mug/1. for CH3H4PteGlu. In pregnancy the mean serum values were 0.23 mug/1. for PteGlu, 0.66 mjg/1. for CH3H4PteGlu, and with folate deficiency 0.30 mug/1. for PteGlu, 0.49 mug/1. for CH3H4PteGlu. Mean urinary folate binding was minimal (less than 0.5 mug/1.), and red cell haemolysate similarly revealed very low binding on exhaustive dialysis. Column chromatography showed that tracer doses of [14C]PteGlu added to serum migrated distally to the protein zone; [14C]CH3H4PteGlu similarly showed no evidence of protein binding. On a sucrose gradient [14C]PteGlu also separated clear of the protein zone."} {"id": "PMID:1259923", "title": "Inhibitors of plasminogen activation in human blood.", "content": "Plasma contained two inhibitors of plasminogen activation by urokinase when fractioned by gel filtration on Sephadex G-200. The inhibitor in the lower molecular weight fractions was separate from the principal protease inhibitors of plasma: alpha1-antitrypsin, alpha2-macroglobulin, C1 inactivator and antithrombin III, and from factor XIII. This activation inhibitor was present in both plasma and serum and its recovery was not reduced by preincubating the serum for 6 h at 37 degrees C. Its inhibitory activity was stable for several days at 4 degrees C, and was enhanced in the presence of an increased saline concentration. Preparations of the inhibitor, active in a clot lysis system, failed to inhibit the esterase activity of urokinase on N-alpha-acetyl-glycyl-L-lysine methyl ester.", "contents": "Inhibitors of plasminogen activation in human blood. Plasma contained two inhibitors of plasminogen activation by urokinase when fractioned by gel filtration on Sephadex G-200. The inhibitor in the lower molecular weight fractions was separate from the principal protease inhibitors of plasma: alpha1-antitrypsin, alpha2-macroglobulin, C1 inactivator and antithrombin III, and from factor XIII. This activation inhibitor was present in both plasma and serum and its recovery was not reduced by preincubating the serum for 6 h at 37 degrees C. Its inhibitory activity was stable for several days at 4 degrees C, and was enhanced in the presence of an increased saline concentration. Preparations of the inhibitor, active in a clot lysis system, failed to inhibit the esterase activity of urokinase on N-alpha-acetyl-glycyl-L-lysine methyl ester."} {"id": "PMID:1259924", "title": "Significance of haematological parameters in the non-Hodgkin's malignant lymphomas.", "content": "Blood findings at diagnosis, in 140 adults with lymphoma, were correlated with bone marrow involvement and survival. An abnormal haemoglobin, leucocyte count or platelet count was found in 57% of patients. Lymphocytopenia occurred in 46%. All patients with thrombocytopenia or neutropenia, 69% with leucopenia and 63% with anaemia had marrow involvement with lymphoma. Marrow involvement in histiocytic and stem cell lymphoma was always associated with anaemia. Marrow involvement in poorly differentiated lymphocytic lymphoma (PDL) was associated with anaemia, thrombocytopenia, leucopenia, lymphocytopenia or lymphoma cells in the blood in 93% of patients. Bone marrow involvement was found in only 13% of patients with normal haematological parameters. In the absence of marrow involvement blood abnormalities at diagnosis did not generally correlate with survival. However, among patients with diffuse PDL who had marrow involvement, anaemia, thrombocytopenia and leucopenia adversely affected survival. Lymphocytopenia did not correlate with survival.", "contents": "Significance of haematological parameters in the non-Hodgkin's malignant lymphomas. Blood findings at diagnosis, in 140 adults with lymphoma, were correlated with bone marrow involvement and survival. An abnormal haemoglobin, leucocyte count or platelet count was found in 57% of patients. Lymphocytopenia occurred in 46%. All patients with thrombocytopenia or neutropenia, 69% with leucopenia and 63% with anaemia had marrow involvement with lymphoma. Marrow involvement in histiocytic and stem cell lymphoma was always associated with anaemia. Marrow involvement in poorly differentiated lymphocytic lymphoma (PDL) was associated with anaemia, thrombocytopenia, leucopenia, lymphocytopenia or lymphoma cells in the blood in 93% of patients. Bone marrow involvement was found in only 13% of patients with normal haematological parameters. In the absence of marrow involvement blood abnormalities at diagnosis did not generally correlate with survival. However, among patients with diffuse PDL who had marrow involvement, anaemia, thrombocytopenia and leucopenia adversely affected survival. Lymphocytopenia did not correlate with survival."} {"id": "PMID:1259925", "title": "Studies on pure red cell aplasia. Maintenance therapy with immunosuppressive drugs.", "content": "Two patients with pure red cell aplasia, whose marrow cells were capable of increasing their rate of haem synthesis when incubated in vitro with erythropoietin concentrate, had a complete remission associated with the administration of cyclophosphamide and prednisone. Both patients relapsed when the drugs were withdrawn. The patients again went into remission when therapy was reinstituted. Maintenance of normal erythropoiesis was dependent on the continued administration of these drugs. This study provides additional evidence for a causal relationship between immunosuppressive therapy and the resumption of erythropoiesis in patients with this disease and demonstrates the value of this therapy for the maintenance of a remission.", "contents": "Studies on pure red cell aplasia. Maintenance therapy with immunosuppressive drugs. Two patients with pure red cell aplasia, whose marrow cells were capable of increasing their rate of haem synthesis when incubated in vitro with erythropoietin concentrate, had a complete remission associated with the administration of cyclophosphamide and prednisone. Both patients relapsed when the drugs were withdrawn. The patients again went into remission when therapy was reinstituted. Maintenance of normal erythropoiesis was dependent on the continued administration of these drugs. This study provides additional evidence for a causal relationship between immunosuppressive therapy and the resumption of erythropoiesis in patients with this disease and demonstrates the value of this therapy for the maintenance of a remission."} {"id": "PMID:1259926", "title": "The Kenya form of hereditary persistence of fetal haemoglobin: structural studies and evidence for homogeneous distribution of haemoglobin F using fluorescent anti-haemoglobin F antibodies.", "content": "Several members of a Ugandan family were heterozygous for the gamma beta fusion gene of Haemoglobin Kenya. Levels of Hb Kenya were significantly higher than those in subjects of previous reports, ranging from 20.68 to 23.35% of the total haemoglobin. The individuals had also 5-8% Hb F, consisting solely of alpha and Ggamma chains. Investigation of the distribution of Hb F among the red cells of Hb Kenya heterozygotes, using monospecific antibodies absorbed against pure Hb Kenya and rendered fluorescent by conjugation with fluorescein isothiocyanate, showed the presence of fetal haemoglobin in all red cells. The data suggest that the phenotype of the Hb Kenya trait resembles that of the Ggamma form of hereditary persistence of fetal haemoglobin rather than that of thalassaemia.", "contents": "The Kenya form of hereditary persistence of fetal haemoglobin: structural studies and evidence for homogeneous distribution of haemoglobin F using fluorescent anti-haemoglobin F antibodies. Several members of a Ugandan family were heterozygous for the gamma beta fusion gene of Haemoglobin Kenya. Levels of Hb Kenya were significantly higher than those in subjects of previous reports, ranging from 20.68 to 23.35% of the total haemoglobin. The individuals had also 5-8% Hb F, consisting solely of alpha and Ggamma chains. Investigation of the distribution of Hb F among the red cells of Hb Kenya heterozygotes, using monospecific antibodies absorbed against pure Hb Kenya and rendered fluorescent by conjugation with fluorescein isothiocyanate, showed the presence of fetal haemoglobin in all red cells. The data suggest that the phenotype of the Hb Kenya trait resembles that of the Ggamma form of hereditary persistence of fetal haemoglobin rather than that of thalassaemia."} {"id": "PMID:1259927", "title": "Heterozygous beta thalassaemia of unusual severity.", "content": "The proband of each of three families of Northern European or Italian extraction had an unusual form of heterozygous beta-thalassaemia, confirmed by haematological, genetic and peripheral blood globin synthesis studies. The unusual severity of this disorder was indicated by chronic haemolysis leading to splenectomy and cholecystectomy, by numerous nucleated red cells and reticulocytes in the peripheral blood, and by leg ulcers in one family. The diversity of clinical expression in many family members with heterozygous beta-thalassaemia was striking. Bone marrow examination in the probands showed numerous large inclusion bodies of the type usually found only in thalassaemia major. In addition, there was unbalanced globin synthesis in the bone marrow, in contrast to the more balanced synthesis found in asymptomatic beta-thalassaemia trait. The amount of newly synthesized alpha-chain found in the free alpha-chain pool was markedly elevated. The unbalanced globin synthesis and alpha-chain inclusions in the bone marrow cells suggest that the severity of the disorder in these patients may be due to the inability of their red cell precursors to fully compensate for the thalassaemic defect or to remove excess alpha-chains. The diversity of clinical expression suggests the influence of undefined acquired or genetic factors on the expression of beta-thalassaemia in these families.", "contents": "Heterozygous beta thalassaemia of unusual severity. The proband of each of three families of Northern European or Italian extraction had an unusual form of heterozygous beta-thalassaemia, confirmed by haematological, genetic and peripheral blood globin synthesis studies. The unusual severity of this disorder was indicated by chronic haemolysis leading to splenectomy and cholecystectomy, by numerous nucleated red cells and reticulocytes in the peripheral blood, and by leg ulcers in one family. The diversity of clinical expression in many family members with heterozygous beta-thalassaemia was striking. Bone marrow examination in the probands showed numerous large inclusion bodies of the type usually found only in thalassaemia major. In addition, there was unbalanced globin synthesis in the bone marrow, in contrast to the more balanced synthesis found in asymptomatic beta-thalassaemia trait. The amount of newly synthesized alpha-chain found in the free alpha-chain pool was markedly elevated. The unbalanced globin synthesis and alpha-chain inclusions in the bone marrow cells suggest that the severity of the disorder in these patients may be due to the inability of their red cell precursors to fully compensate for the thalassaemic defect or to remove excess alpha-chains. The diversity of clinical expression suggests the influence of undefined acquired or genetic factors on the expression of beta-thalassaemia in these families."} {"id": "PMID:1259928", "title": "The pattern of fetal haemoglobin disappearance after birth.", "content": "Haemoglobin F (Hb F) levels were determined in 209 full-term newborn babies or infants of different ages ranging from birth to 11 months. A follow-up study of the disappearance of Hb F after birth was carried out on 25 premature babies; they were followed periodically from birth until 8 months. The results obtained in both samples show that Hb F levels remain constant after birth for periods varying from about 15 d in at term babies to about 40 d in premature babies; a linear decrease follows in both cases. The initial plateau is a finding contrary to what has been reported. A possible model for the phenomenon is discussed in terms of haemoglobin genes and ontogenetic differentiation.", "contents": "The pattern of fetal haemoglobin disappearance after birth. Haemoglobin F (Hb F) levels were determined in 209 full-term newborn babies or infants of different ages ranging from birth to 11 months. A follow-up study of the disappearance of Hb F after birth was carried out on 25 premature babies; they were followed periodically from birth until 8 months. The results obtained in both samples show that Hb F levels remain constant after birth for periods varying from about 15 d in at term babies to about 40 d in premature babies; a linear decrease follows in both cases. The initial plateau is a finding contrary to what has been reported. A possible model for the phenomenon is discussed in terms of haemoglobin genes and ontogenetic differentiation."} {"id": "PMID:1259930", "title": "Induction of haemolytic anaemia by substituted phenylhydrazines.", "content": "The induction of anaemia and reticulocytosis by arylhydrazines was influenced by substituents on the benzene ring of phenylhydrazine. Arylhydrazines with ortho substituents, which would hinder the binding by haemoglobin of a ligand derived from the arylhydrazine, resulted in the least anaemia and reticulocytosis. These results are consistent with a previous finding that hydrazinobenzoic acid, which did not produce a ferrihaemochrome from ferrihaemoglobin, did not induce anaemia. The parallelism between the formation of a ferrihaemoglobin compound and the induction of anaemia supports the hypothesis that destabilization of haemoglobin by the binding of a ligand derived from the aryl portion of an arylhydrazine is an essential step in arylhydrazine-induced haemolytic anaemia.", "contents": "Induction of haemolytic anaemia by substituted phenylhydrazines. The induction of anaemia and reticulocytosis by arylhydrazines was influenced by substituents on the benzene ring of phenylhydrazine. Arylhydrazines with ortho substituents, which would hinder the binding by haemoglobin of a ligand derived from the arylhydrazine, resulted in the least anaemia and reticulocytosis. These results are consistent with a previous finding that hydrazinobenzoic acid, which did not produce a ferrihaemochrome from ferrihaemoglobin, did not induce anaemia. The parallelism between the formation of a ferrihaemoglobin compound and the induction of anaemia supports the hypothesis that destabilization of haemoglobin by the binding of a ligand derived from the aryl portion of an arylhydrazine is an essential step in arylhydrazine-induced haemolytic anaemia."} {"id": "PMID:1259931", "title": "Assay of thalassaemic messenger RNA in the wheat germ system.", "content": "Messenger RNA(mRNA) has been prepared from reticulocytes obtained from patients with different types of thalassaemia and assayed in the wheat germ system. Since normal human reticulocyte mRNA directs the synthesis of equal numbers of alpha- and beta-globin chains in this system it offers a rapid and simple technique for assaying mRNA in the thalassaemic disorders. In mRNA from beta+ thalassaemics the deficiency of beta-globin synthesis mirrored that observed in intact reticulocytes while that prepared from patients wiht haemoglobin H disease gave alpha/beta globin chain production ratios which showed consistently greater imbalance than was found in reticulocytes. Messenger RNA prepared from haemoglobin E-beta0 thalassaemics from Thailand directed no detectable beta-chain synthesis while that prepared from a betaO thalassaemic from Ferrara synthesized a fraction with the chromatographic characteristics of beta-globin chains.", "contents": "Assay of thalassaemic messenger RNA in the wheat germ system. Messenger RNA(mRNA) has been prepared from reticulocytes obtained from patients with different types of thalassaemia and assayed in the wheat germ system. Since normal human reticulocyte mRNA directs the synthesis of equal numbers of alpha- and beta-globin chains in this system it offers a rapid and simple technique for assaying mRNA in the thalassaemic disorders. In mRNA from beta+ thalassaemics the deficiency of beta-globin synthesis mirrored that observed in intact reticulocytes while that prepared from patients wiht haemoglobin H disease gave alpha/beta globin chain production ratios which showed consistently greater imbalance than was found in reticulocytes. Messenger RNA prepared from haemoglobin E-beta0 thalassaemics from Thailand directed no detectable beta-chain synthesis while that prepared from a betaO thalassaemic from Ferrara synthesized a fraction with the chromatographic characteristics of beta-globin chains."} {"id": "PMID:1259932", "title": "Chemotaxis for human monocytes by fibrinogen-derived peptides.", "content": "Chemotactic activity for human peripheral blood monocytes was generated by the action of thrombin on human fibrinogen, a reaction known to release low molecular fibrinopeptides. Supernatants prepared by incubating Contortrix venom with fibrinogen, which cleaves the B peptide, were also chemotactic, whereas no activity was present in supernatants from Arvin venom, which cleaves peptides A, AP and AY. Thus fibrinopeptide B was chemotactic for the monocyte in addition to the neutrophil, as previously reported. Monocyte chemotactic activity was also generated by the action of plasmin on human fibrinogen and shown to be associated with the D and E fragments but not with a mixture of fragments X and Y. When plasmin digestion was stopped at time intervals up to 24 h, monocyte chemotactic activity corresponded with the appearance of the D and E fragments. The monocyte chemotactic activity, contained in a 24 h digest, eluted from Sephadex G-75 at VO, corresponding to the expected position of the D and E fragments whereas neutrophil chemotactic activity eluted with molecules of molecular size of approximately 30 000 daltons. Thus fragments D and E derived from plasmin digestion of fibrinogen attract the monocyte whereas only the small uncharacterized peptides were chemotactic for the neutrophil. These different profiles of chemotactic activity for the neutrophil and the monocyte in terms of plasmin digestion products of fibrinogen may be of significance in the events leading to the accumulation of these cells in vivo during fibrin deposition.", "contents": "Chemotaxis for human monocytes by fibrinogen-derived peptides. Chemotactic activity for human peripheral blood monocytes was generated by the action of thrombin on human fibrinogen, a reaction known to release low molecular fibrinopeptides. Supernatants prepared by incubating Contortrix venom with fibrinogen, which cleaves the B peptide, were also chemotactic, whereas no activity was present in supernatants from Arvin venom, which cleaves peptides A, AP and AY. Thus fibrinopeptide B was chemotactic for the monocyte in addition to the neutrophil, as previously reported. Monocyte chemotactic activity was also generated by the action of plasmin on human fibrinogen and shown to be associated with the D and E fragments but not with a mixture of fragments X and Y. When plasmin digestion was stopped at time intervals up to 24 h, monocyte chemotactic activity corresponded with the appearance of the D and E fragments. The monocyte chemotactic activity, contained in a 24 h digest, eluted from Sephadex G-75 at VO, corresponding to the expected position of the D and E fragments whereas neutrophil chemotactic activity eluted with molecules of molecular size of approximately 30 000 daltons. Thus fragments D and E derived from plasmin digestion of fibrinogen attract the monocyte whereas only the small uncharacterized peptides were chemotactic for the neutrophil. These different profiles of chemotactic activity for the neutrophil and the monocyte in terms of plasmin digestion products of fibrinogen may be of significance in the events leading to the accumulation of these cells in vivo during fibrin deposition."} {"id": "PMID:1259933", "title": "The role of membrane bound complement in the aggregation of mammalian platelets by collagen.", "content": "Platelets from dogs decomplemented with purified Cobra Venom Factor (CVF) lose the ability to aggregate in response to collagen stimulation. In vitro in man, dog and rabbit, and in vivo in the dog, CVF abolishes the collagen response of platelets, the effect being dose-related. Resuspension of CVF inactivated platelets in plasma containing complement resulted in a total return of sensitivity to collagen. Examination of CVF inactivated platelets with the electron microscope failed to show any marked difference from control platelets. Serotonin granules were still present and the platelets retained a discoid appearance. Incubation of platelets with antibodies to C1, C3 and C5 resulted in inhibition of the collagen response: this effect was dose-related. Light microscopy indicated that DVF does not affect the adhesion of platelets to collagen but appears to prevent subsequent aggregation. It is suggested that the complement system is involved in the induction of the platelet release reaction by collagen, and that inhibition by CVF and anticomplement antibodies is the result of a blocking of the release reaction.", "contents": "The role of membrane bound complement in the aggregation of mammalian platelets by collagen. Platelets from dogs decomplemented with purified Cobra Venom Factor (CVF) lose the ability to aggregate in response to collagen stimulation. In vitro in man, dog and rabbit, and in vivo in the dog, CVF abolishes the collagen response of platelets, the effect being dose-related. Resuspension of CVF inactivated platelets in plasma containing complement resulted in a total return of sensitivity to collagen. Examination of CVF inactivated platelets with the electron microscope failed to show any marked difference from control platelets. Serotonin granules were still present and the platelets retained a discoid appearance. Incubation of platelets with antibodies to C1, C3 and C5 resulted in inhibition of the collagen response: this effect was dose-related. Light microscopy indicated that DVF does not affect the adhesion of platelets to collagen but appears to prevent subsequent aggregation. It is suggested that the complement system is involved in the induction of the platelet release reaction by collagen, and that inhibition by CVF and anticomplement antibodies is the result of a blocking of the release reaction."} {"id": "PMID:1259934", "title": "Residual marrow damage: possible explanation for idiosyncrasy to chloramphenicol.", "content": "The effect of oral administration of chloramphenicol was studied in normal mice and mice having residual marrow damage. In the concentration used the drug had no detectable effect on the marrow of normal mice but caused a progressive fall in the numbers of pluripotential stem cells and granulocytic progenitor cells in mice bearing residual marrow damage. However, cells taken from such mice were no more sensitive than normal cells to the in vitro action of chloramphenicol. The results suggest that unrecognized residual marrow damage can be an aetiological factor in marrow failure due to drug idiosyncrasy.", "contents": "Residual marrow damage: possible explanation for idiosyncrasy to chloramphenicol. The effect of oral administration of chloramphenicol was studied in normal mice and mice having residual marrow damage. In the concentration used the drug had no detectable effect on the marrow of normal mice but caused a progressive fall in the numbers of pluripotential stem cells and granulocytic progenitor cells in mice bearing residual marrow damage. However, cells taken from such mice were no more sensitive than normal cells to the in vitro action of chloramphenicol. The results suggest that unrecognized residual marrow damage can be an aetiological factor in marrow failure due to drug idiosyncrasy."} {"id": "PMID:1259935", "title": "A controlled trial of androgen therapy in experimental chronic hypoplastic marrow failure.", "content": "A controlled trial of an androgen, 17-nortestosterone decanoate, was carried out to test its effect as therapy in an experimental model of chronic hypoplastic marrow failure. No effect was detected.", "contents": "A controlled trial of androgen therapy in experimental chronic hypoplastic marrow failure. A controlled trial of an androgen, 17-nortestosterone decanoate, was carried out to test its effect as therapy in an experimental model of chronic hypoplastic marrow failure. No effect was detected."} {"id": "PMID:1259936", "title": "Distribution of granulopoietic activity in the human skeleton, studied by colony growth in agar diffusion chambers.", "content": "The colony forming ability of bone marrow cells from 110 haematologically normal patients was investigated by their growth in semi-solid agar in intraperitoneal diffusion chambers. Marrow aspirated from the sternum showed a consistently higher colony yield than that from the iliac crest. Study of site variation in the individual was possible in donors for bone marrow transplantation. In each of four cases, sternal marrow produced more colonies than any other site. Examination of smears made from the aspirated samples suggested that the difference in yield was not due to varying dilution by peripheral blood on aspiration from different sites. It is concluded, therefore, that the incidence of colony precursor cells is not uniform throughout the active marrow.", "contents": "Distribution of granulopoietic activity in the human skeleton, studied by colony growth in agar diffusion chambers. The colony forming ability of bone marrow cells from 110 haematologically normal patients was investigated by their growth in semi-solid agar in intraperitoneal diffusion chambers. Marrow aspirated from the sternum showed a consistently higher colony yield than that from the iliac crest. Study of site variation in the individual was possible in donors for bone marrow transplantation. In each of four cases, sternal marrow produced more colonies than any other site. Examination of smears made from the aspirated samples suggested that the difference in yield was not due to varying dilution by peripheral blood on aspiration from different sites. It is concluded, therefore, that the incidence of colony precursor cells is not uniform throughout the active marrow."} {"id": "PMID:1259937", "title": "Growth of mouse yolk sac cells cultured in vivo.", "content": "The proliferation and differentiation of yolk sac cells from 10 1/2-day-old mouse embryos were studied in diffusion chambers implanted into syngeneic and allogeneic hosts. The most striking observation was the appearance, proliferation and predominance of immature and mature plasma cells. The data suggested that the differentiation into plasma cells and the rate of growth of yolk sac cells cultured in vivo may be dependent on the genetics of the strain of mouse and host. This demonstration of differentiation of plasma cells from yolk sac cells cultured in vivo adds further information to the origin and ontogeny of potentially immunocompetent cells.", "contents": "Growth of mouse yolk sac cells cultured in vivo. The proliferation and differentiation of yolk sac cells from 10 1/2-day-old mouse embryos were studied in diffusion chambers implanted into syngeneic and allogeneic hosts. The most striking observation was the appearance, proliferation and predominance of immature and mature plasma cells. The data suggested that the differentiation into plasma cells and the rate of growth of yolk sac cells cultured in vivo may be dependent on the genetics of the strain of mouse and host. This demonstration of differentiation of plasma cells from yolk sac cells cultured in vivo adds further information to the origin and ontogeny of potentially immunocompetent cells."} {"id": "PMID:1259938", "title": "Erythrocytosis associated with diffuse parenchymal lesions of the kidney.", "content": "Thirteen patients with diffuse parenchymal disease of the kidney and erythrocytosis are reported. In five the haematocrit was only minimally elevated because of an associated increase in plasma volume. The erythrocytosis in three patients was of particular interest: (1) transient appearance in a 23-year-old man with glomerulonephritis; (2) persistence despite the partial remission of nephrotic state in a 19-year-old man; (3) appearance following removal of a nephrosclerotic kidney from a 54-year-old woman. Because an associated expansion of plasma volume is not uncommon with parenchymal renal disease, it is suggested that the only reliable screening method for renal erythrocytosis is direct measurement of red cell volume.", "contents": "Erythrocytosis associated with diffuse parenchymal lesions of the kidney. Thirteen patients with diffuse parenchymal disease of the kidney and erythrocytosis are reported. In five the haematocrit was only minimally elevated because of an associated increase in plasma volume. The erythrocytosis in three patients was of particular interest: (1) transient appearance in a 23-year-old man with glomerulonephritis; (2) persistence despite the partial remission of nephrotic state in a 19-year-old man; (3) appearance following removal of a nephrosclerotic kidney from a 54-year-old woman. Because an associated expansion of plasma volume is not uncommon with parenchymal renal disease, it is suggested that the only reliable screening method for renal erythrocytosis is direct measurement of red cell volume."} {"id": "PMID:1259939", "title": "Fine structural studies of peripheral blood leucocytes from children with kwashiorkor: morphological and functional properties.", "content": "This is the first report of electron microscopic observation on circulating leucocytes from children with kwashiorkor, Neutrophils showed evidence of immaturity, prominent Golgi zones, granule pleomorphism; strands of endoplasmic reticulum and D\u00f6hle bodies were frequent. Although an in vitro microbicidal defect occurs with S. aureus, E. coli and C. albicans, the postphagocytic morphological events, including vacuole formation and degranulation, were normal. In mononuclear cell pellets plasmacytoid cells were frequently observed, and rare lymphoblasts occurred. The findings suggest activation of the phagocytic system and stimulation of humoral immunity in children with kwashiorkor. These fine structural observations are comparable to those which occur in trauma or thermal injury, both conditions associated with tissue breakdown and extensive antigenic stimulation.", "contents": "Fine structural studies of peripheral blood leucocytes from children with kwashiorkor: morphological and functional properties. This is the first report of electron microscopic observation on circulating leucocytes from children with kwashiorkor, Neutrophils showed evidence of immaturity, prominent Golgi zones, granule pleomorphism; strands of endoplasmic reticulum and D\u00f6hle bodies were frequent. Although an in vitro microbicidal defect occurs with S. aureus, E. coli and C. albicans, the postphagocytic morphological events, including vacuole formation and degranulation, were normal. In mononuclear cell pellets plasmacytoid cells were frequently observed, and rare lymphoblasts occurred. The findings suggest activation of the phagocytic system and stimulation of humoral immunity in children with kwashiorkor. These fine structural observations are comparable to those which occur in trauma or thermal injury, both conditions associated with tissue breakdown and extensive antigenic stimulation."} {"id": "PMID:1259940", "title": "Ferritin and sideroblastic anaemias: inhibition of protein synthesis by protease contaminants in commercial preparations of ferritin.", "content": "Commercial preparations of ferritin inhibited reticulocyte-lysate cell-free protein synthesis and disaggregated polyribosomes to monoribosomes and ribosomal subunits. These effects were prevented by addition of reduced glutathione (GSH) to the incubation medium, but ferritin did not lower GSH concentration in the lysates. The more purified the ferritin preparation, the less inhibition of protein synthesis was observed. These data suggested that the effect was due to a contamination of the ferritin with proteolytic activity. In confirmation of this proposal we demonstrated that there was protease activity in both the 2X and 5X crystalized ferritin preparations, with 2.5 times greater activity in the 2X preparation. The proteolytic activity in ferritin was inhibited by incubation with the protease inhibitor tosyl lysine chloromethyl ketone (TLCK). When an amount of trypsin equivalent to the protease activity of the ferritin was added to the incubation mixture, similar effects on protein synthesis and the ribosome-polyribosome component were found. Both GSH and TLCK prevented these effects of trypsin. These data suggest that the previously reported effect of ferritin on reticulocyte cell-free protein synthesis was due to contamination of the ferritin by a protease. It appears that ferritin does not play a direct role in the pathogenesis of sideroblastic anaemias.", "contents": "Ferritin and sideroblastic anaemias: inhibition of protein synthesis by protease contaminants in commercial preparations of ferritin. Commercial preparations of ferritin inhibited reticulocyte-lysate cell-free protein synthesis and disaggregated polyribosomes to monoribosomes and ribosomal subunits. These effects were prevented by addition of reduced glutathione (GSH) to the incubation medium, but ferritin did not lower GSH concentration in the lysates. The more purified the ferritin preparation, the less inhibition of protein synthesis was observed. These data suggested that the effect was due to a contamination of the ferritin with proteolytic activity. In confirmation of this proposal we demonstrated that there was protease activity in both the 2X and 5X crystalized ferritin preparations, with 2.5 times greater activity in the 2X preparation. The proteolytic activity in ferritin was inhibited by incubation with the protease inhibitor tosyl lysine chloromethyl ketone (TLCK). When an amount of trypsin equivalent to the protease activity of the ferritin was added to the incubation mixture, similar effects on protein synthesis and the ribosome-polyribosome component were found. Both GSH and TLCK prevented these effects of trypsin. These data suggest that the previously reported effect of ferritin on reticulocyte cell-free protein synthesis was due to contamination of the ferritin by a protease. It appears that ferritin does not play a direct role in the pathogenesis of sideroblastic anaemias."} {"id": "PMID:1259941", "title": "Radioimmunoassay studies of the cross-reacting antibody of human group O sera.", "content": "Cross-reacting antibody was obtained from three recently stimulated group O donors. The biological reactions of cross-reacting antibody were investigated by a study of the binding characteristics of 125I-labelled purified IgG fractions with red cells and by the reactions of whole antiserum or eluates with 125I-labelled blood group glycoproteins. The bulk of cross-reacting antibody activity is restricted to the IgG fraction. Experiments with 125I-labelled IgG and with the radioimmunoassay system revealed that cross-reacting antibody has a higher binding constant than specific anti-A or anti-B. In the radioimmunoassay system complete inhibition of cross-reaction antibody was obtained either with D-galactose or with N-acetyl-D-galactosamine, but the same concentrations of monosaccharides gave only partial inhibition of specific anti-A and anti-B antibodies. The results indicate that cross-reacting antibody binds to a smaller determinant than specific antibody. Investigations with other monosaccharides did not, however, reveal a common inhibitory structure. The ability of cross-reacting antibody to bind to both group A and B antigens may, therefore, be a property of a 'polyfunctional' antibody binding site.", "contents": "Radioimmunoassay studies of the cross-reacting antibody of human group O sera. Cross-reacting antibody was obtained from three recently stimulated group O donors. The biological reactions of cross-reacting antibody were investigated by a study of the binding characteristics of 125I-labelled purified IgG fractions with red cells and by the reactions of whole antiserum or eluates with 125I-labelled blood group glycoproteins. The bulk of cross-reacting antibody activity is restricted to the IgG fraction. Experiments with 125I-labelled IgG and with the radioimmunoassay system revealed that cross-reacting antibody has a higher binding constant than specific anti-A or anti-B. In the radioimmunoassay system complete inhibition of cross-reaction antibody was obtained either with D-galactose or with N-acetyl-D-galactosamine, but the same concentrations of monosaccharides gave only partial inhibition of specific anti-A and anti-B antibodies. The results indicate that cross-reacting antibody binds to a smaller determinant than specific antibody. Investigations with other monosaccharides did not, however, reveal a common inhibitory structure. The ability of cross-reacting antibody to bind to both group A and B antigens may, therefore, be a property of a 'polyfunctional' antibody binding site."} {"id": "PMID:1259942", "title": "The role of continuous flow centrifuge leucapheresis in the management of chronic lymphocytic leukaemia.", "content": "Continuous flow centrifuge leucapheresis (CFCL) provides a simple, mechanical technique for removing large numbers of circulating lymphocytes without cytotoxicity. Seven sequences of CFCL were performed on six patients with chronic lymphocytic leukaemia (CLL). In six, the median course consisted of six procedures in 10 days. A median total of 27.7 X 10(11) leucocytes were removed and a 70% drop in leucocyte counts (from 433 X 10(9)/l. to 130 X 10(9)/l.) was observed with little fall in haemoglobin and platelet counts. Tissue massess decreased in two patients. A similar effect was seen in one patient managed less intensively with 21 procedures being performed over 73 days, removing a total of 87.6 X 10(11) leucocytes. The peripheral leucocyte count decreased from 760 X 10(9)/l. to 114 X 10(9)/l. and hepatomegaly diminished markedly. One patient has survived for over 9 months since CFCL but stayed in control only briefly after each of two courses. Short courses of daily CFCL can produce short-term benefit in the management of advanced CLL but at present its main value is as an investigational form of therapy which provides a unique opportunity to study the cytokinetics of advanced CLL without the complications of superimposed cytotoxic therapy.", "contents": "The role of continuous flow centrifuge leucapheresis in the management of chronic lymphocytic leukaemia. Continuous flow centrifuge leucapheresis (CFCL) provides a simple, mechanical technique for removing large numbers of circulating lymphocytes without cytotoxicity. Seven sequences of CFCL were performed on six patients with chronic lymphocytic leukaemia (CLL). In six, the median course consisted of six procedures in 10 days. A median total of 27.7 X 10(11) leucocytes were removed and a 70% drop in leucocyte counts (from 433 X 10(9)/l. to 130 X 10(9)/l.) was observed with little fall in haemoglobin and platelet counts. Tissue massess decreased in two patients. A similar effect was seen in one patient managed less intensively with 21 procedures being performed over 73 days, removing a total of 87.6 X 10(11) leucocytes. The peripheral leucocyte count decreased from 760 X 10(9)/l. to 114 X 10(9)/l. and hepatomegaly diminished markedly. One patient has survived for over 9 months since CFCL but stayed in control only briefly after each of two courses. Short courses of daily CFCL can produce short-term benefit in the management of advanced CLL but at present its main value is as an investigational form of therapy which provides a unique opportunity to study the cytokinetics of advanced CLL without the complications of superimposed cytotoxic therapy."} {"id": "PMID:1259943", "title": "The regulation of protein synthesis in animal cells by serum factors.", "content": "We have investigated the regulation of protein synthesis in animal cells by serum factors. Withdrawal of serum from the medium of actively dividing Vero cells resulted in an immediate decline in the rate of peptide chain elongation (Hassell and Engelhardt, 1973). Assay of elongation factor I (EFI) activity in the post-ribosomal supernatant as well as that associated with the ribosomes revealed that serum deprivation resulted also in reduction in the activity of this factor. The decline in the activity of EFI after serum deprivation occurred to the same extent and at the same time as the decline in the in vivo rate of protein synthesis and the in vitro peptide synthetic capacity of cell-free extracts. A temporal correlation therefore exists among the in vivo rate of protein synthesis, the peptide synthetic activity of cell-free extracts, and the activity of EFI. The activity of peptidyl transferase was not altered by serum deprivation. The loss of extract peptide synthetic activity resulting from serum deprivation was reversible since serum addition to previously serum-starved cultures resulted in full restoration of activity for polyphenylalanine (polyPhe) synthesis within 3 h. Moreover, RNA synthesis was not required for this turn-on of polyPhe synthesis. Vased on these data we conclude that a translational control mechanism is operative in Vero cells deprived of serum.", "contents": "The regulation of protein synthesis in animal cells by serum factors. We have investigated the regulation of protein synthesis in animal cells by serum factors. Withdrawal of serum from the medium of actively dividing Vero cells resulted in an immediate decline in the rate of peptide chain elongation (Hassell and Engelhardt, 1973). Assay of elongation factor I (EFI) activity in the post-ribosomal supernatant as well as that associated with the ribosomes revealed that serum deprivation resulted also in reduction in the activity of this factor. The decline in the activity of EFI after serum deprivation occurred to the same extent and at the same time as the decline in the in vivo rate of protein synthesis and the in vitro peptide synthetic capacity of cell-free extracts. A temporal correlation therefore exists among the in vivo rate of protein synthesis, the peptide synthetic activity of cell-free extracts, and the activity of EFI. The activity of peptidyl transferase was not altered by serum deprivation. The loss of extract peptide synthetic activity resulting from serum deprivation was reversible since serum addition to previously serum-starved cultures resulted in full restoration of activity for polyphenylalanine (polyPhe) synthesis within 3 h. Moreover, RNA synthesis was not required for this turn-on of polyPhe synthesis. Vased on these data we conclude that a translational control mechanism is operative in Vero cells deprived of serum."} {"id": "PMID:1259944", "title": "A calorimetric and fluorescent probe study of the gel-liquid crystalline phase transition in small, single-lamellar dipalmitoylphosphatidylcholine vesicles.", "content": "The results of a calorimetric and fluorescent probe study of the thermotropic behavior of various types of dispersions of dipalmitolphosphatidylcholine bilayer vesicles are reported. Bangham-type, multilamellar vesicles exhibit tow distinct phase transitions at 34.6 and 41.2 degrees C. On the other hand, single-lamellar spherical vesicles appear to exhibit a single transition at 37 degrees C. The single-lamellar vesicles are thermodynamically unstable below 27 degrees C and slowly transform into a multilamellar structure with a single phase transition of 41.2 degrees C. These transformed structures resemble, but are not identical with, Bangham-type vesicles. An experimentally testable thermodynamic and kinetic model based upon these results is developed.", "contents": "A calorimetric and fluorescent probe study of the gel-liquid crystalline phase transition in small, single-lamellar dipalmitoylphosphatidylcholine vesicles. The results of a calorimetric and fluorescent probe study of the thermotropic behavior of various types of dispersions of dipalmitolphosphatidylcholine bilayer vesicles are reported. Bangham-type, multilamellar vesicles exhibit tow distinct phase transitions at 34.6 and 41.2 degrees C. On the other hand, single-lamellar spherical vesicles appear to exhibit a single transition at 37 degrees C. The single-lamellar vesicles are thermodynamically unstable below 27 degrees C and slowly transform into a multilamellar structure with a single phase transition of 41.2 degrees C. These transformed structures resemble, but are not identical with, Bangham-type vesicles. An experimentally testable thermodynamic and kinetic model based upon these results is developed."} {"id": "PMID:1259945", "title": "Proton nuclear magnetic resonance studies of hemoglobin Malm\u00f6: implications of mutations at homologous positions of the alpha and beta chains.", "content": "The abnormal human hemoglobin Malm\u00f6 (beta97FG4 His leads to Gln) has been studied and its properties are compared with those of normal adult hemoglobin A. The data presented here show that the ring-current shifted proton resonances of both HbCO and HbO2 Malm\u00f6 are very different from the corresponding forms of Hb A. The hyperfine shifted proton resonances of deoxy-Hb Malm\u00f6 do not differ drastically from those of deoxy-Hb A. This result, together with the finding that the exchangeable proton resonances of the deoxy form of the two hemoglobins are similar, suggests that unliganded Hb Malm\u00f6 can assume a deoxy-like quaternary structure both in the absence and presence of organic phosphates We have also compared the properties of Hb Malm\u00f6 with those of Hb Chesapeake (alpha92FG4 Arg leads to Leu). This allows us to study the properties of two abnormal human hemoglobins with mutations at homologous positions of the alpha and beta chains in the three-dimenstional structure of the hemoglobin molecule. Our present results suggest that the mutaion at betaFG4 has its greatest effect on the teritiary structure of the heme pocket of the liganded forms of the hemoglobin while the mutation at alphaFG4 alters the deoxy structure of the hemoglogin molecule but does not alter the teriary structure of the heme pockets of the liganded form of the hemoglobin molecule. Both hemoglobins undergo a transition from the deoxy (T) to the oxy (R) quaternary structure upon ligation. The abnormally high oxygen affinities and low cooperativities of these two hemoglobins must therefore be due to either the structural differences which we have observed and/or to an altered transition between the T and R structures.", "contents": "Proton nuclear magnetic resonance studies of hemoglobin Malm\u00f6: implications of mutations at homologous positions of the alpha and beta chains. The abnormal human hemoglobin Malm\u00f6 (beta97FG4 His leads to Gln) has been studied and its properties are compared with those of normal adult hemoglobin A. The data presented here show that the ring-current shifted proton resonances of both HbCO and HbO2 Malm\u00f6 are very different from the corresponding forms of Hb A. The hyperfine shifted proton resonances of deoxy-Hb Malm\u00f6 do not differ drastically from those of deoxy-Hb A. This result, together with the finding that the exchangeable proton resonances of the deoxy form of the two hemoglobins are similar, suggests that unliganded Hb Malm\u00f6 can assume a deoxy-like quaternary structure both in the absence and presence of organic phosphates We have also compared the properties of Hb Malm\u00f6 with those of Hb Chesapeake (alpha92FG4 Arg leads to Leu). This allows us to study the properties of two abnormal human hemoglobins with mutations at homologous positions of the alpha and beta chains in the three-dimenstional structure of the hemoglobin molecule. Our present results suggest that the mutaion at betaFG4 has its greatest effect on the teritiary structure of the heme pocket of the liganded forms of the hemoglobin while the mutation at alphaFG4 alters the deoxy structure of the hemoglogin molecule but does not alter the teriary structure of the heme pockets of the liganded form of the hemoglobin molecule. Both hemoglobins undergo a transition from the deoxy (T) to the oxy (R) quaternary structure upon ligation. The abnormally high oxygen affinities and low cooperativities of these two hemoglobins must therefore be due to either the structural differences which we have observed and/or to an altered transition between the T and R structures."} {"id": "PMID:1259946", "title": "Binding of rabbit muscle aldolase to band 3, the predominant polypeptide of the human erythrocyte membrane.", "content": "Aldolase is a trace protein in isolated human red cell membrane preparations. Following total elution of the endogenous enzyme by a saline wash, the interaction of this membrane with rabbit muscle aldolase was studied. At saturation, exogenous aldolase constituted over 40% of the repleted membrane protein. Scatchard analysis revealed two classes of sites, each numbering approximately 7 X 10(5) per ghost. Specificity was suggested by the exclusive binding of the enzyme to the membrane's inner (cytoplasmic) surface. Furthermore, milimolar levels of fructose 1,6-bisphosphate eluted the enzyme from ghosts, while fructose 6-phosphate and NADH (a metabolite which elutes human erythrocyte glyceraldehyde-3-phosphate dehydrogenase (G3PD) from its binding site) were ineffectuve. Removing peripheral membrane proteins with EDTA and lithium 3,5-diiodosalicylate did not diminish the binding capacity of the membranes. An aldolase-band 3 complex, dissociable by high ionic strength or fructose 1,6-bisphosphate treatment, was demonstrated in Triton X-100 extracts of repleted membranes by rate zonal sedimentation analysis on sucrose gradients. We conclude that the association of rabbit muscle aldolase with isolated human erythrocyte membranes reflects its specific binding to band 3 at the cytoplasmic surface, as is also true of G3PD.", "contents": "Binding of rabbit muscle aldolase to band 3, the predominant polypeptide of the human erythrocyte membrane. Aldolase is a trace protein in isolated human red cell membrane preparations. Following total elution of the endogenous enzyme by a saline wash, the interaction of this membrane with rabbit muscle aldolase was studied. At saturation, exogenous aldolase constituted over 40% of the repleted membrane protein. Scatchard analysis revealed two classes of sites, each numbering approximately 7 X 10(5) per ghost. Specificity was suggested by the exclusive binding of the enzyme to the membrane's inner (cytoplasmic) surface. Furthermore, milimolar levels of fructose 1,6-bisphosphate eluted the enzyme from ghosts, while fructose 6-phosphate and NADH (a metabolite which elutes human erythrocyte glyceraldehyde-3-phosphate dehydrogenase (G3PD) from its binding site) were ineffectuve. Removing peripheral membrane proteins with EDTA and lithium 3,5-diiodosalicylate did not diminish the binding capacity of the membranes. An aldolase-band 3 complex, dissociable by high ionic strength or fructose 1,6-bisphosphate treatment, was demonstrated in Triton X-100 extracts of repleted membranes by rate zonal sedimentation analysis on sucrose gradients. We conclude that the association of rabbit muscle aldolase with isolated human erythrocyte membranes reflects its specific binding to band 3 at the cytoplasmic surface, as is also true of G3PD."} {"id": "PMID:1259947", "title": "The resolution of Ascaris cuticle collagen into three chain types.", "content": "Reduced and methylated collagen from Ascaris lumbricoides cuticle was resolved into three major components by chromatography on phosphocellulose. The components have similar molecular weights of about 52,000 by sedimentation equilbrium and molecular sieve chromatography, but they have different amino acid compositions. Since they do not appear to be stoichiometrically related, they apparently represent chains from collagens of more than one type. All three chains contain about 27 residue % glycine, 36 residues of proline, and 17 residues of methylcysteine, suggesting that the collagens can be maximally about 80% triple helical and are extensively disulfide cross-linked in the native state. Two minor components from the cuticle are apparently derived from one of the major chains by cleavage in a single region to give two-third and one-third fragments.", "contents": "The resolution of Ascaris cuticle collagen into three chain types. Reduced and methylated collagen from Ascaris lumbricoides cuticle was resolved into three major components by chromatography on phosphocellulose. The components have similar molecular weights of about 52,000 by sedimentation equilbrium and molecular sieve chromatography, but they have different amino acid compositions. Since they do not appear to be stoichiometrically related, they apparently represent chains from collagens of more than one type. All three chains contain about 27 residue % glycine, 36 residues of proline, and 17 residues of methylcysteine, suggesting that the collagens can be maximally about 80% triple helical and are extensively disulfide cross-linked in the native state. Two minor components from the cuticle are apparently derived from one of the major chains by cleavage in a single region to give two-third and one-third fragments."} {"id": "PMID:1259948", "title": "Iodination of Xenopus laevis histone F2a1 in chromatin.", "content": "The reaction of calf thymus and Xenopus laevis histones with radioactive iodine has been studied under various conditions that affect chromatin structure. All histones from both species contain at least one tyrosine residue and, in a denaturing solvent, all the the histones react with iodine. Histone F2a1 has been studied in detail. Calf thymus F2a1 is known to contain four tyrosyls and all four react with iodine. In high voltage paper electrophoresis, the tyrosine-containing peptides from calf co-migrate with those from Xenopus F2a1, suggesting that the amino acid sequence is strongly conserved between these two species. Therefore, the published calf thymus F2a1 sequence has been used to order the Xenopus F2a1 peptides within the molecules. When gently isolated native chromatin is iodinated in a low ionic strength medium 60% of the radioactivity in F2a1 is in tyrosyl 88, 30% in tyrosyl 51, and tyrosyl 72 and 98 have almost no radioactivity. Reagents which remove the protein from the DNA (2 M NaCl) or partially disrupt protein tertiary structure (5 M urea) increase the reactivity of each of the four tyrosyls five- to tenfold, suggesting that all four are protected about equally by the overall folding of the chromatin. Isolated F2a1 iodinated in the presence of 10 M urea shows uniform labeling in each of the four peptides, suggesting that tyrosyl 72 and 98 are afforded some protection solely by protein-protein interactions. The stepwise removal of histones in increasing NaCl concentrations differentially increases the availability of each F2a1 tyrosyl. The preferential exposure of tyrosyl 88 coincides with the removal of the majority of F1 histones at 0.5 M NaCl while the gradual and stepwise increase in reactivity of tyrosyl 51, 72, and 98 correlates with the gradual removal of histones other than F1. Radioactive iodination of chromatin has been shown to be a sensitive probe for detecting changes in the association state (or conformation) of histone F2a1.", "contents": "Iodination of Xenopus laevis histone F2a1 in chromatin. The reaction of calf thymus and Xenopus laevis histones with radioactive iodine has been studied under various conditions that affect chromatin structure. All histones from both species contain at least one tyrosine residue and, in a denaturing solvent, all the the histones react with iodine. Histone F2a1 has been studied in detail. Calf thymus F2a1 is known to contain four tyrosyls and all four react with iodine. In high voltage paper electrophoresis, the tyrosine-containing peptides from calf co-migrate with those from Xenopus F2a1, suggesting that the amino acid sequence is strongly conserved between these two species. Therefore, the published calf thymus F2a1 sequence has been used to order the Xenopus F2a1 peptides within the molecules. When gently isolated native chromatin is iodinated in a low ionic strength medium 60% of the radioactivity in F2a1 is in tyrosyl 88, 30% in tyrosyl 51, and tyrosyl 72 and 98 have almost no radioactivity. Reagents which remove the protein from the DNA (2 M NaCl) or partially disrupt protein tertiary structure (5 M urea) increase the reactivity of each of the four tyrosyls five- to tenfold, suggesting that all four are protected about equally by the overall folding of the chromatin. Isolated F2a1 iodinated in the presence of 10 M urea shows uniform labeling in each of the four peptides, suggesting that tyrosyl 72 and 98 are afforded some protection solely by protein-protein interactions. The stepwise removal of histones in increasing NaCl concentrations differentially increases the availability of each F2a1 tyrosyl. The preferential exposure of tyrosyl 88 coincides with the removal of the majority of F1 histones at 0.5 M NaCl while the gradual and stepwise increase in reactivity of tyrosyl 51, 72, and 98 correlates with the gradual removal of histones other than F1. Radioactive iodination of chromatin has been shown to be a sensitive probe for detecting changes in the association state (or conformation) of histone F2a1."} {"id": "PMID:1259949", "title": "The effect of carboxymethylating a single methionine residue on the subunit interactions of glycophorin A.", "content": "Human red cell glycophorin A shows an equilibrium between dimeric and monomeric forms which have been disignated PAS-1 and PAS-2, respectively. This equilibrium, which is dependent upon protein concentration is achieved by incubation in sodium dodecyl sulfate solutions at elevated temperatures and is assayed by sodium dodecyl sulfate gel electrophoresis. Carboxymethylation of glycophorin A in guanidine hydrochloride or urea alters the interactions between polypeptide chains so that the lower molecular weight form (PAS-2) is obtained much more readily. If the carboxymethylation is performed at pH 3.0 the reaction is limited to the two methionine residues of glycophorin A which are located at positions 8 and 81 in the sequence. In the presence of sodium dodecyl sulfate, only one of the two methionine residues is carboxymethylated, and glycoprotein modified under these conditions does not exhibit the change in electrophoretic mobility. Experiments with [1-14C]iodoacetic acid demonstrated that Met-81, located in the hydrophobic domain of the protein, is the residue protected by sodium dodecyl sulfate. Modification of Met-81 destabilizes the dimeric form relative to the monomer by weakening the interactions between polypeptide chains. The experiments described in this paper confirm that the hydrophobic domain of glycophorin A is involved in subunit interactions and that Met-81 plays a critical role in those interactions.", "contents": "The effect of carboxymethylating a single methionine residue on the subunit interactions of glycophorin A. Human red cell glycophorin A shows an equilibrium between dimeric and monomeric forms which have been disignated PAS-1 and PAS-2, respectively. This equilibrium, which is dependent upon protein concentration is achieved by incubation in sodium dodecyl sulfate solutions at elevated temperatures and is assayed by sodium dodecyl sulfate gel electrophoresis. Carboxymethylation of glycophorin A in guanidine hydrochloride or urea alters the interactions between polypeptide chains so that the lower molecular weight form (PAS-2) is obtained much more readily. If the carboxymethylation is performed at pH 3.0 the reaction is limited to the two methionine residues of glycophorin A which are located at positions 8 and 81 in the sequence. In the presence of sodium dodecyl sulfate, only one of the two methionine residues is carboxymethylated, and glycoprotein modified under these conditions does not exhibit the change in electrophoretic mobility. Experiments with [1-14C]iodoacetic acid demonstrated that Met-81, located in the hydrophobic domain of the protein, is the residue protected by sodium dodecyl sulfate. Modification of Met-81 destabilizes the dimeric form relative to the monomer by weakening the interactions between polypeptide chains. The experiments described in this paper confirm that the hydrophobic domain of glycophorin A is involved in subunit interactions and that Met-81 plays a critical role in those interactions."} {"id": "PMID:1259950", "title": "Characterization of the gamma subunits of the 7S nerve growth factor complex.", "content": "The gamma subunits of the 7S nerve growth factor complex (7S NGF) display arginine esteropeptidase activity. By varying the conditions of electrophoresis in acrylamide gel, it has been demonstrated that the gamma-subunit fraction of 7S NGF contains five different proteins, in contrast to the three (gamma1, gamma2, and gamma3) originally described (Smith, A.P., Varon, S. and Shooter, E.M. (1968), Biochemistry 7, 3259-3268); the gamma1 and gamma2 subunits, previously thought to be single species, can each be resolved into two components. The two components of the gamma1 subunit have the same isoelectric point, as do the two components of the gamma2 subunit. The distribution of protein among the two components of each of the gamma1 and gamma2 subunits varied from preparation to preparation. Moreover, a shift in the distribution for the gamma1 subunit was accompanied by a parallel shift for the gamma2 subunit. All of the different gamma proteins have the same molecular weight. On the basis of the molecular weights of the peptide chains of the gamma subunits and of the species which are formed by cross-linking with dimethyl suberimidate, it was concluded, that both the gamma1 and gamma2 subunits contain one species with two peptide chains and another with three peptide chains, while the gamma3 subunit is a single species with three peptide chains. The results also suggest that two of the chains in the three-chain species are derived, by proteolytic cleavage, from the larger chain in the two-chain species.", "contents": "Characterization of the gamma subunits of the 7S nerve growth factor complex. The gamma subunits of the 7S nerve growth factor complex (7S NGF) display arginine esteropeptidase activity. By varying the conditions of electrophoresis in acrylamide gel, it has been demonstrated that the gamma-subunit fraction of 7S NGF contains five different proteins, in contrast to the three (gamma1, gamma2, and gamma3) originally described (Smith, A.P., Varon, S. and Shooter, E.M. (1968), Biochemistry 7, 3259-3268); the gamma1 and gamma2 subunits, previously thought to be single species, can each be resolved into two components. The two components of the gamma1 subunit have the same isoelectric point, as do the two components of the gamma2 subunit. The distribution of protein among the two components of each of the gamma1 and gamma2 subunits varied from preparation to preparation. Moreover, a shift in the distribution for the gamma1 subunit was accompanied by a parallel shift for the gamma2 subunit. All of the different gamma proteins have the same molecular weight. On the basis of the molecular weights of the peptide chains of the gamma subunits and of the species which are formed by cross-linking with dimethyl suberimidate, it was concluded, that both the gamma1 and gamma2 subunits contain one species with two peptide chains and another with three peptide chains, while the gamma3 subunit is a single species with three peptide chains. The results also suggest that two of the chains in the three-chain species are derived, by proteolytic cleavage, from the larger chain in the two-chain species."} {"id": "PMID:1259951", "title": "The nature of stacking interations in polynucleotides. Molecular states in Oligo- and polyribocytidylic acids by relaxation analysis.", "content": "The dynamics of the helix-coil transition of single-stranded poly(C) (polyribocytidylate) and CpC (cytidyly(3'-5')cytosine) was investigated by an improved cable temperature-jump technique. The single-strand relaxation was characterized by following the ultraviolet (uv) absorbance changes at 248 and 280 nm. Poly(C) and CpC showed single relaxation processes with amplitudes corresponding to those expected from equilibrium melting curves. The relaxation time contants in the range of 25-100 ns were independent of the nucleotide concentration, but strongly dependent upon temperature. Using thermodynanic parameters obtained from circular dichroism (CD) and uv absorbance melting curves, the following rate constants k (at 20 degrees C, 1.05 M ionic strength, pH 7) and activation enthalpies EA were calculated for poly (C): helix formation kR = 1.11 X 10(-7) s-1 (EAR = 2.6 kcal); helix dissociation kD = 2.1 X 10(6) s-1 (EAD = 11.9 kcal). The rate constants obtained for CpC were higher by a factor of about 2 in kR and 12 in kD, whereas the activation enthalpies closely corresponded to those found for the polymer. In addition to the single-stranded helix-coil relaxation, poly(C) and CpC exhibit a relaxation process with a time constant below 25 ns and maximum amplitudes at wavelengths lambda greater than or equal to 285 nm. The same process is found in cytidine and is attributed to hydration equilibria. The hydration reaction can be considered to be in equilibrium during the entire time range of the helix-coil transition and thus the data obtained for the helix-coil transition can be described by a simple two-state model. The rate parameters indicate the existence of relatively high energy barriers in the helix-coil transition and provide strong evidence evidence against an oscillating dimer model. If there is an ensemble of substates for one of the states (as may be expected for the coil form), the energy difference between the populated substates is small compared with the energy difference between the major conformational states.", "contents": "The nature of stacking interations in polynucleotides. Molecular states in Oligo- and polyribocytidylic acids by relaxation analysis. The dynamics of the helix-coil transition of single-stranded poly(C) (polyribocytidylate) and CpC (cytidyly(3'-5')cytosine) was investigated by an improved cable temperature-jump technique. The single-strand relaxation was characterized by following the ultraviolet (uv) absorbance changes at 248 and 280 nm. Poly(C) and CpC showed single relaxation processes with amplitudes corresponding to those expected from equilibrium melting curves. The relaxation time contants in the range of 25-100 ns were independent of the nucleotide concentration, but strongly dependent upon temperature. Using thermodynanic parameters obtained from circular dichroism (CD) and uv absorbance melting curves, the following rate constants k (at 20 degrees C, 1.05 M ionic strength, pH 7) and activation enthalpies EA were calculated for poly (C): helix formation kR = 1.11 X 10(-7) s-1 (EAR = 2.6 kcal); helix dissociation kD = 2.1 X 10(6) s-1 (EAD = 11.9 kcal). The rate constants obtained for CpC were higher by a factor of about 2 in kR and 12 in kD, whereas the activation enthalpies closely corresponded to those found for the polymer. In addition to the single-stranded helix-coil relaxation, poly(C) and CpC exhibit a relaxation process with a time constant below 25 ns and maximum amplitudes at wavelengths lambda greater than or equal to 285 nm. The same process is found in cytidine and is attributed to hydration equilibria. The hydration reaction can be considered to be in equilibrium during the entire time range of the helix-coil transition and thus the data obtained for the helix-coil transition can be described by a simple two-state model. The rate parameters indicate the existence of relatively high energy barriers in the helix-coil transition and provide strong evidence evidence against an oscillating dimer model. If there is an ensemble of substates for one of the states (as may be expected for the coil form), the energy difference between the populated substates is small compared with the energy difference between the major conformational states."} {"id": "PMID:1259952", "title": "HeLa cell deoxyribonucleic acid dependent RNA polymerases: function and properties of the class III enzymes.", "content": "The class III DNA dependent RNA polymerases (nucleoside triphosphate:RNA nucleotidyltransferase EC 2.7.7.6 from HeLa cells have been solubilized and characterized as to function and properties. Two chromatographically distinct forms of enzyme III, designated polymerases IIIA and IIIB, can be resolved when cell extracts are chromatographed on DEAE-Sephadex columns. Enzymes IIIA and IIIB exhibit nearly identical catalytic properties such as divalent cation stimulation, broad biphasic ammonium sulfate optima, and characteristic alpha-amanitin sensitivities which clearly distinguish them from the homologous enzymes, forms I and II. Polymerases IIIA and IIIB are both primarily localized in the nucleus (greater than 60%). The most notable characteristic of the class III enzymes is a unique sensitivity to inhibition by alpha-amanitin (50% inhibition at 15 mug/ml). HeLa cell enzyme I is not inhibited by the mushroom toxin even at very high concentrations (greater than 400 mug/ml), while HeLa cell polymerase II is inhibited by very low concentrations of amanitin (50% inhibition at 0.003 mug/ml). The three major classes of enzyme (I, II, III) exhibit characteristic sensitivities to alpha-amanitin whether assayed in nuclei, crude homogenates, or in a chromatographically purified state. Using a nuclear in vitro RNA synthesizing system to investigate the alpha-amanitin sensitivities of the synthesis of tRNA precursor (4.5S pre-tRNA) and 5S ribosomal RNA, it was found that the synthesis of these RNA species was inhibited 50% at 15 mug/ml of alpha-amanitin. The alpha-amanitin inhibition curves for the synthesis of pre-tRNA-5S ribosomal RNA in nuclei and the alpha-amanitin titration curves for the partially purified class III enzymes (IIIA and IIIB) are identical. These data, therefore, show that the in vivo functional role of the class III RNA polymerases (IIIA-IIIB) is the transcription of the genes coding for transfer RNA and 5S ribosomal RNA.", "contents": "HeLa cell deoxyribonucleic acid dependent RNA polymerases: function and properties of the class III enzymes. The class III DNA dependent RNA polymerases (nucleoside triphosphate:RNA nucleotidyltransferase EC 2.7.7.6 from HeLa cells have been solubilized and characterized as to function and properties. Two chromatographically distinct forms of enzyme III, designated polymerases IIIA and IIIB, can be resolved when cell extracts are chromatographed on DEAE-Sephadex columns. Enzymes IIIA and IIIB exhibit nearly identical catalytic properties such as divalent cation stimulation, broad biphasic ammonium sulfate optima, and characteristic alpha-amanitin sensitivities which clearly distinguish them from the homologous enzymes, forms I and II. Polymerases IIIA and IIIB are both primarily localized in the nucleus (greater than 60%). The most notable characteristic of the class III enzymes is a unique sensitivity to inhibition by alpha-amanitin (50% inhibition at 15 mug/ml). HeLa cell enzyme I is not inhibited by the mushroom toxin even at very high concentrations (greater than 400 mug/ml), while HeLa cell polymerase II is inhibited by very low concentrations of amanitin (50% inhibition at 0.003 mug/ml). The three major classes of enzyme (I, II, III) exhibit characteristic sensitivities to alpha-amanitin whether assayed in nuclei, crude homogenates, or in a chromatographically purified state. Using a nuclear in vitro RNA synthesizing system to investigate the alpha-amanitin sensitivities of the synthesis of tRNA precursor (4.5S pre-tRNA) and 5S ribosomal RNA, it was found that the synthesis of these RNA species was inhibited 50% at 15 mug/ml of alpha-amanitin. The alpha-amanitin inhibition curves for the synthesis of pre-tRNA-5S ribosomal RNA in nuclei and the alpha-amanitin titration curves for the partially purified class III enzymes (IIIA and IIIB) are identical. These data, therefore, show that the in vivo functional role of the class III RNA polymerases (IIIA-IIIB) is the transcription of the genes coding for transfer RNA and 5S ribosomal RNA."} {"id": "PMID:1259953", "title": "Solubilization of an alpha-bungarotoxin-binding component from rat brain.", "content": "Binding of [125I]-alpha-bungarotoxin to rat brain was investigated. Picomole quantities of specific toxin binding sites per gram of fresh tissue were found in particulate preparations as well as detergent extracts of whole brain. The toxin-binding macromolecules can be solubilized in low concentrations of Triton X-100. Specific binding occurs to a single class of sites with a dissociation constant of 5.6 X 10(-11) M. The association rate constant in 10 mM sodium phosphate, pH 7.4, was determined to be 6.8 X 10(5) M-1 s-1; the half-life of the complex was found to be 5.1 h, corresponding to a dissociation rate constant of 3.8 X 10(-5) s-1. The binding macromolecules resemble peripheral nicotinic acetylcholine receptors in toxin binding kinetics, solubility, isoelectric point, and hydrodynamic properties.", "contents": "Solubilization of an alpha-bungarotoxin-binding component from rat brain. Binding of [125I]-alpha-bungarotoxin to rat brain was investigated. Picomole quantities of specific toxin binding sites per gram of fresh tissue were found in particulate preparations as well as detergent extracts of whole brain. The toxin-binding macromolecules can be solubilized in low concentrations of Triton X-100. Specific binding occurs to a single class of sites with a dissociation constant of 5.6 X 10(-11) M. The association rate constant in 10 mM sodium phosphate, pH 7.4, was determined to be 6.8 X 10(5) M-1 s-1; the half-life of the complex was found to be 5.1 h, corresponding to a dissociation rate constant of 3.8 X 10(-5) s-1. The binding macromolecules resemble peripheral nicotinic acetylcholine receptors in toxin binding kinetics, solubility, isoelectric point, and hydrodynamic properties."} {"id": "PMID:1259954", "title": "Translocation and binding of adenine nucleotides by rat liver mitochondria partially depleted of phospholipids.", "content": "1. Rat liver mitochondria were partially depleted of their phospholipids using phospholipase A prepared from porcine pancreas (substrate specificity, cardiolipin greater than phosphatidylethanolamine greater than phosphatidylcholine) or from Crotalus adamanteus venom (substrate specificity, phosphatidylethanolamine = phosphatidylcholine greater than cardiolipin). 2. Removal of only about 1% of the mitochondrial phospholipid with the pancreatic enzyme leads to 50% and 25% losses in ADP and ATP translocation, respectively. Concomitant with the loss in translocation is a decline in the ability of both carbonylcyanide m-chlorophenylhydrazone and Ca2+ to stimulate ATP translocation. 3. To achieve comparable losses in ADP and ATP translocation with the venom enzyme, it is necessary to remove about 8% of the total mitochondrial phospholipid. Following such treatment, carbonylcyanide m-chlorophenylhydrazone and Ca2+ are still capable of stimulating ATP translocation. 4. Control experiments involving treatment of the mitochondria with the products of phospholipase digestion indicate that the effects observed on the translocase reflect a loss of phospholipid from the membrane. 5. Binding studies indicate that the loss in adenine nucleotide translocation following phospholipase treatment cannot be accoundted for by an altered ability to bind adenine nucleotides to atractyloside-sensitive sites. 6. The data are interpreted in terms of a mechanism of adenine nucleotide translocation involving a lipoprotein carrier system, consisting of the translocator protein and phospholipids, possibly cardiolipin and phosphatidylethanolamine.", "contents": "Translocation and binding of adenine nucleotides by rat liver mitochondria partially depleted of phospholipids. 1. Rat liver mitochondria were partially depleted of their phospholipids using phospholipase A prepared from porcine pancreas (substrate specificity, cardiolipin greater than phosphatidylethanolamine greater than phosphatidylcholine) or from Crotalus adamanteus venom (substrate specificity, phosphatidylethanolamine = phosphatidylcholine greater than cardiolipin). 2. Removal of only about 1% of the mitochondrial phospholipid with the pancreatic enzyme leads to 50% and 25% losses in ADP and ATP translocation, respectively. Concomitant with the loss in translocation is a decline in the ability of both carbonylcyanide m-chlorophenylhydrazone and Ca2+ to stimulate ATP translocation. 3. To achieve comparable losses in ADP and ATP translocation with the venom enzyme, it is necessary to remove about 8% of the total mitochondrial phospholipid. Following such treatment, carbonylcyanide m-chlorophenylhydrazone and Ca2+ are still capable of stimulating ATP translocation. 4. Control experiments involving treatment of the mitochondria with the products of phospholipase digestion indicate that the effects observed on the translocase reflect a loss of phospholipid from the membrane. 5. Binding studies indicate that the loss in adenine nucleotide translocation following phospholipase treatment cannot be accoundted for by an altered ability to bind adenine nucleotides to atractyloside-sensitive sites. 6. The data are interpreted in terms of a mechanism of adenine nucleotide translocation involving a lipoprotein carrier system, consisting of the translocator protein and phospholipids, possibly cardiolipin and phosphatidylethanolamine."} {"id": "PMID:1259955", "title": "Ferrous ion-mediated cytochrome P-450 degradation and lipid peroxidation in adrenal cortex mitochondria.", "content": "The relationship between the degradation reaction of cytochrome P-450 and lipid peroxidation was studied utilizing bovine adrenal cortex mitochondria. The two reactions were found to be closely correlated in terms of their response to storage of the mitochondrial preparation, stimulation by Fe2+, inhibition by EDTA and their initiation by cumene hydroperoxide. Both reactions were also found not to be inhibited by catalase, superoxide dismutase, 1,4-diazabicyclo-(2,2,2)-octane and alcohols, indicating that H2O2, superoxide, singlet oxygen and hydroxyl radicals do not participate in these reactions. Yet, diphenylamine proved to be a powerful inhibitor for both reactions, suggesting the involvement of a radical species. Cumene hydroperoxide could induce these two reactions at below 0.1 mM concentrations in the presence of molecular oxygen. The chemiluminescence observed during the Fe2+-mediated lipid peroxidation reaction which was not inhibited by either superoxide dismutase or 1,4-diazabicyclo-(2,2,2)-octane, was biphasic: one was a rapid burst; and the other was a slowly increasing emission. The latter portion of the emission of light coincided with the formation of malondialdehyde. These results indicate that in adrenal cortex mitochondria the degradation of cytochrome P-450 is closely related to lipid peroxidation.", "contents": "Ferrous ion-mediated cytochrome P-450 degradation and lipid peroxidation in adrenal cortex mitochondria. The relationship between the degradation reaction of cytochrome P-450 and lipid peroxidation was studied utilizing bovine adrenal cortex mitochondria. The two reactions were found to be closely correlated in terms of their response to storage of the mitochondrial preparation, stimulation by Fe2+, inhibition by EDTA and their initiation by cumene hydroperoxide. Both reactions were also found not to be inhibited by catalase, superoxide dismutase, 1,4-diazabicyclo-(2,2,2)-octane and alcohols, indicating that H2O2, superoxide, singlet oxygen and hydroxyl radicals do not participate in these reactions. Yet, diphenylamine proved to be a powerful inhibitor for both reactions, suggesting the involvement of a radical species. Cumene hydroperoxide could induce these two reactions at below 0.1 mM concentrations in the presence of molecular oxygen. The chemiluminescence observed during the Fe2+-mediated lipid peroxidation reaction which was not inhibited by either superoxide dismutase or 1,4-diazabicyclo-(2,2,2)-octane, was biphasic: one was a rapid burst; and the other was a slowly increasing emission. The latter portion of the emission of light coincided with the formation of malondialdehyde. These results indicate that in adrenal cortex mitochondria the degradation of cytochrome P-450 is closely related to lipid peroxidation."} {"id": "PMID:1259956", "title": "The ratio of the two light reactions and their coupling in chloroplasts.", "content": "The kinetics of the absorbance changes of chlorophyll alphaI (P-700) and plastoquinone induced by xenon flashes of saturating intensity were studied in spinach chloroplasts. 1. The total amount of chlorophyll alphaI is compared with that amount being reduced via the rate-limiting step between the light reactions. This is based on the amplitudes of the absorbance changes of chlorophyll alphaI after chemical reduction and after a group of flashes following far-red preillumination. It is concluded that only 75% of chlorophyll alphaI is coupled to chlorophyll alphaII via linear electron transport and that the remaining 25% is functionally isolated. 2. A ratio of 0.85 for coupled chlorophyll alphaI to chlorophyll alphaII is estimated from the time course of the absorbance changes of plastoquinone and chlorophyll alphaI in two independent ways. 3. The oxygen yield per flash is used to calculate the difference extinction coefficient of chlorophyll alphaI at the maximum of the red absorbance band in spinach chloroplasts: delta xi703 = (6.7 +/- 0.7)-10(4) M-1-cm-1. The assumption of a quantitative electron transfer from water via plastoquinone to coupled chlorophyll alphaI is supported by the same extinction coefficient reported by Hiyama and Ke for Photosystem I particles. The location and function of the different chlorophylls alphaI is discussed in detail.", "contents": "The ratio of the two light reactions and their coupling in chloroplasts. The kinetics of the absorbance changes of chlorophyll alphaI (P-700) and plastoquinone induced by xenon flashes of saturating intensity were studied in spinach chloroplasts. 1. The total amount of chlorophyll alphaI is compared with that amount being reduced via the rate-limiting step between the light reactions. This is based on the amplitudes of the absorbance changes of chlorophyll alphaI after chemical reduction and after a group of flashes following far-red preillumination. It is concluded that only 75% of chlorophyll alphaI is coupled to chlorophyll alphaII via linear electron transport and that the remaining 25% is functionally isolated. 2. A ratio of 0.85 for coupled chlorophyll alphaI to chlorophyll alphaII is estimated from the time course of the absorbance changes of plastoquinone and chlorophyll alphaI in two independent ways. 3. The oxygen yield per flash is used to calculate the difference extinction coefficient of chlorophyll alphaI at the maximum of the red absorbance band in spinach chloroplasts: delta xi703 = (6.7 +/- 0.7)-10(4) M-1-cm-1. The assumption of a quantitative electron transfer from water via plastoquinone to coupled chlorophyll alphaI is supported by the same extinction coefficient reported by Hiyama and Ke for Photosystem I particles. The location and function of the different chlorophylls alphaI is discussed in detail."} {"id": "PMID:1259957", "title": "[Changes in adenosine phosphates and energy charge in chloroplastic and nonchloroplastic compartments of wheat leaves (author's transl)].", "content": "Changes in the adenine nucleotides and energy charge (= (ATP)+1/2(ADP)/(AMP)+(ADP)+(ATP)) levels were studied in chloroplastic and non-chloroplastic compartments using non-aqueously isolated wheat leaves chloroplasts. The two adenine nucleotides pools (of chloroplasts and non-chloroplastic part of the cell), though distinct, are linked. This linkage substantiates an energy-rich bond exchange between the two compartments. When both photphosphorylation and oxidative phosphorylation occur simultaneously, energy charge takes high values, generally higher than 0.80. When neither oxidative phosphorylation nor photophosphorylation occur, energy charge is very low and takes values generally lower than 0.45. When one compartment alone produces approximately P, energy charge in the two compartments takes intermediate values which remain relatively high. Dark-light transition in nitrogen resulted in changes of the AMP, ADP and ATP levels which quickly reach a steady state. Chloroplast energy charge shifts rapidly from 0.45 to 0.75 in 10 s; after 1 min it reaches 0.86, a value that corresponds to a steady level. In the cytoplasm, energy charge changes from 0.44 to 0.71 in 1 min. Energy charge increase in the non-chloroplastic compartment substantiates an energy transfer from chloroplasts to the cytoplasm. On nitrogen-air transition in the dark, the cytoplasm energy charge reaches a steady level in 30 s. In chloroplasts, it also increases but slowly. There is indeed a transfer of energy from cytoplasm to chloroplasts. Darkening of the leaves in air causes a drastic and lasting drop of energy charge in the chloroplasts where it has a low value after 5 min in the dark. Then it increases again but slowly and is still lower than 0.70 after 10 min in the dark. Meanwhile, energy charge in cytoplasm keeps values higher than 0.75. Metabolic regulation by energy charge and control of adenine nucleotides level by adenylate kinase (EC 2.7.4.3) are discussed.", "contents": "[Changes in adenosine phosphates and energy charge in chloroplastic and nonchloroplastic compartments of wheat leaves (author's transl)]. Changes in the adenine nucleotides and energy charge (= (ATP)+1/2(ADP)/(AMP)+(ADP)+(ATP)) levels were studied in chloroplastic and non-chloroplastic compartments using non-aqueously isolated wheat leaves chloroplasts. The two adenine nucleotides pools (of chloroplasts and non-chloroplastic part of the cell), though distinct, are linked. This linkage substantiates an energy-rich bond exchange between the two compartments. When both photphosphorylation and oxidative phosphorylation occur simultaneously, energy charge takes high values, generally higher than 0.80. When neither oxidative phosphorylation nor photophosphorylation occur, energy charge is very low and takes values generally lower than 0.45. When one compartment alone produces approximately P, energy charge in the two compartments takes intermediate values which remain relatively high. Dark-light transition in nitrogen resulted in changes of the AMP, ADP and ATP levels which quickly reach a steady state. Chloroplast energy charge shifts rapidly from 0.45 to 0.75 in 10 s; after 1 min it reaches 0.86, a value that corresponds to a steady level. In the cytoplasm, energy charge changes from 0.44 to 0.71 in 1 min. Energy charge increase in the non-chloroplastic compartment substantiates an energy transfer from chloroplasts to the cytoplasm. On nitrogen-air transition in the dark, the cytoplasm energy charge reaches a steady level in 30 s. In chloroplasts, it also increases but slowly. There is indeed a transfer of energy from cytoplasm to chloroplasts. Darkening of the leaves in air causes a drastic and lasting drop of energy charge in the chloroplasts where it has a low value after 5 min in the dark. Then it increases again but slowly and is still lower than 0.70 after 10 min in the dark. Meanwhile, energy charge in cytoplasm keeps values higher than 0.75. Metabolic regulation by energy charge and control of adenine nucleotides level by adenylate kinase (EC 2.7.4.3) are discussed."} {"id": "PMID:1259958", "title": "Effects of lipolytic enzymes on the photochemical activities of spinach chloroplasts.", "content": "1. Spinach class II chloroplasts were treated with purified potato lipolytic acyl-hydrolase and venom phospholipase A2, and their lipid degradations and the effects on the photochemical activities were followed. 2. Potato lipolytic enzyme hydrolyzed monogalactosyldiacylglycerol at a faster rate than phospholipids such as phosphatidylglycerol and phosphatidylcholine. The treatment caused a rapid decrease of Photosystem I activity, and a less change of Photosystem II activity. 3. Venom phospholipase A2 which preferentially hydrolyzed phosphatidylglycerol, caused a rapid decrease of Photosystem II activity and only a slight decrease of photosystem I activity. 4. Potato enzyme and phospholipase A2 degraded the membrane lipids of glutaraldehyde-fixed chloroplasts at a rather slightly higher rate than those of non-treated chloroplasts. 5. The results suggested a possible correlation between monogalactosyldiacylglycerol degradation and decay of Photosystem I activity and between phosphatidylglycerol degradation and decay of Photosystem II activity. A possible mechanism is discussed.", "contents": "Effects of lipolytic enzymes on the photochemical activities of spinach chloroplasts. 1. Spinach class II chloroplasts were treated with purified potato lipolytic acyl-hydrolase and venom phospholipase A2, and their lipid degradations and the effects on the photochemical activities were followed. 2. Potato lipolytic enzyme hydrolyzed monogalactosyldiacylglycerol at a faster rate than phospholipids such as phosphatidylglycerol and phosphatidylcholine. The treatment caused a rapid decrease of Photosystem I activity, and a less change of Photosystem II activity. 3. Venom phospholipase A2 which preferentially hydrolyzed phosphatidylglycerol, caused a rapid decrease of Photosystem II activity and only a slight decrease of photosystem I activity. 4. Potato enzyme and phospholipase A2 degraded the membrane lipids of glutaraldehyde-fixed chloroplasts at a rather slightly higher rate than those of non-treated chloroplasts. 5. The results suggested a possible correlation between monogalactosyldiacylglycerol degradation and decay of Photosystem I activity and between phosphatidylglycerol degradation and decay of Photosystem II activity. A possible mechanism is discussed."} {"id": "PMID:1259959", "title": "An abnormal ratio of cytochromes in the respiratory chain of mouse and human myelomas.", "content": "Mouse myeloma cells and mitochondria had the same kinds of cytochrome components in the respiratory chain as the normal ones. Their constitution, however, was abnormally different from that found in normal cells and mitochondria. The cytochrome aa3 concentration was especially low in the myeloma as compared with cytochrome c concentration, and the resulting cytochrome aa3/c ratio was 0.25, which was the lowest ever reported in animal mitochondria. Normal lymph node cells, producing the immunoglobulin similar to the myeloma cells, had a ratio of 1.1. Human myeloma mitochondria had the same characteristics as the mouse myeloma. Ascite form myeloma originated from mouse solid from myeloma grew faster, and yet aa3/c of 0.5 in the ascites myeloma was found to be quite similar to that observed in various ascites tumor cells such as hepatomas, Ehrlich and sarcoma 180. A significant part of the cytochromes in the respiratory chain of the mouse myeloma remained in the oxidized form in the cyanide-inhibited or anaerobic states, and was reduced only by the addition of dithionite. The properties of the b cytochromes in mouse myeloma mitochondria are also described and discussed in the context of multiple forms of the b cytochromes in the respiratory chain.", "contents": "An abnormal ratio of cytochromes in the respiratory chain of mouse and human myelomas. Mouse myeloma cells and mitochondria had the same kinds of cytochrome components in the respiratory chain as the normal ones. Their constitution, however, was abnormally different from that found in normal cells and mitochondria. The cytochrome aa3 concentration was especially low in the myeloma as compared with cytochrome c concentration, and the resulting cytochrome aa3/c ratio was 0.25, which was the lowest ever reported in animal mitochondria. Normal lymph node cells, producing the immunoglobulin similar to the myeloma cells, had a ratio of 1.1. Human myeloma mitochondria had the same characteristics as the mouse myeloma. Ascite form myeloma originated from mouse solid from myeloma grew faster, and yet aa3/c of 0.5 in the ascites myeloma was found to be quite similar to that observed in various ascites tumor cells such as hepatomas, Ehrlich and sarcoma 180. A significant part of the cytochromes in the respiratory chain of the mouse myeloma remained in the oxidized form in the cyanide-inhibited or anaerobic states, and was reduced only by the addition of dithionite. The properties of the b cytochromes in mouse myeloma mitochondria are also described and discussed in the context of multiple forms of the b cytochromes in the respiratory chain."} {"id": "PMID:1259960", "title": "Sulphydryl groups in photosynthetic energy conservation. I. Light-dependent inhibition of photophosphorylation by the sulphydryl reagent 2-2'dithio bis-(5-nitropyridine).", "content": "1. The sulphydryl reagent 2-2'dithio bis-(5-nitropyridine) (DTNP) inhibited photophosphorylation when the chloroplasts were preincubated with the reagent in the light. A maximum inhibition of about 50% was obtained in the presence of pyocyanine and MgCl 2 at 0.3 mumol DTNP per mg chlorophyll and was completed in about 40 s of preillumination. 2. Dithioerythritol, ADP plus Pi (or arsenate) and uncouplers prevented the inhibition when present during the preillumination while phloridzin, Dio-9 and discarine B were ineffective. Low concentrations of ADP or ATP afforded partial protection but other nucleotides had no effect. 3. DTNP inhibited the coupled electron transport rate to the basal level and had no effect on the uncoupled electron transport. The stimulation of proton uptake and inhibition of electron transport by ATP was prevented by DTNP. 4. The trypsin-activated but not the light- and dithioerythritol-triggered ATPase was inhibited by light preincubation of chloroplasts with DTNP. 5. Reversal of DTNP inhibition of photophosphorylation was obtained by a second preillumination in the presence of thiol groups. 6. More DTNP reacted with chloroplasts in the light than in the dark. Two mol of thione were formed in the light per mol of DTNP disappeared. 7. The results suggested that DTNP inhibition is related to the oxidation by DTNP of chloroplast vicinal dithiols probably exposed by a light-induced conformational change.", "contents": "Sulphydryl groups in photosynthetic energy conservation. I. Light-dependent inhibition of photophosphorylation by the sulphydryl reagent 2-2'dithio bis-(5-nitropyridine). 1. The sulphydryl reagent 2-2'dithio bis-(5-nitropyridine) (DTNP) inhibited photophosphorylation when the chloroplasts were preincubated with the reagent in the light. A maximum inhibition of about 50% was obtained in the presence of pyocyanine and MgCl 2 at 0.3 mumol DTNP per mg chlorophyll and was completed in about 40 s of preillumination. 2. Dithioerythritol, ADP plus Pi (or arsenate) and uncouplers prevented the inhibition when present during the preillumination while phloridzin, Dio-9 and discarine B were ineffective. Low concentrations of ADP or ATP afforded partial protection but other nucleotides had no effect. 3. DTNP inhibited the coupled electron transport rate to the basal level and had no effect on the uncoupled electron transport. The stimulation of proton uptake and inhibition of electron transport by ATP was prevented by DTNP. 4. The trypsin-activated but not the light- and dithioerythritol-triggered ATPase was inhibited by light preincubation of chloroplasts with DTNP. 5. Reversal of DTNP inhibition of photophosphorylation was obtained by a second preillumination in the presence of thiol groups. 6. More DTNP reacted with chloroplasts in the light than in the dark. Two mol of thione were formed in the light per mol of DTNP disappeared. 7. The results suggested that DTNP inhibition is related to the oxidation by DTNP of chloroplast vicinal dithiols probably exposed by a light-induced conformational change."} {"id": "PMID:1259961", "title": "Increase effected by calcium ion in the rate of oxygen evolution from preparations of Phormidium luridum.", "content": "The presence of Ca2+ causes a twentyfold or greater increase in the rate of oxygen evolution by cell-free preparations of Phormidium luridum. The requirement for Ca2+ is specific; other divalent cations are much less effective or are inhibitory. The rate of the Hill reaction is maximal at 30 mM CaCl2 in both detergent-free and Brij 35 preparations. The 3-(3,4-dichlorophenyl)-1,1-dimethylurea-insensitive component of oxygen-evolving activity in each preparation also shows the requirement for added Ca2+. This indicates that Ca2+ is acting close to the oxygen-evolving reaction center of Photosystem II. Defatted bovine serum albumin increases the rate of oxygen evolution in the detergent-free preparation, but does not compete with Ca2+, discounting fatty acid mediation of the effects of Ca2+. Neither excess Hill acceptor nor uncouplers of photophosphorylation diminish the stimulatory effects of Ca2+.", "contents": "Increase effected by calcium ion in the rate of oxygen evolution from preparations of Phormidium luridum. The presence of Ca2+ causes a twentyfold or greater increase in the rate of oxygen evolution by cell-free preparations of Phormidium luridum. The requirement for Ca2+ is specific; other divalent cations are much less effective or are inhibitory. The rate of the Hill reaction is maximal at 30 mM CaCl2 in both detergent-free and Brij 35 preparations. The 3-(3,4-dichlorophenyl)-1,1-dimethylurea-insensitive component of oxygen-evolving activity in each preparation also shows the requirement for added Ca2+. This indicates that Ca2+ is acting close to the oxygen-evolving reaction center of Photosystem II. Defatted bovine serum albumin increases the rate of oxygen evolution in the detergent-free preparation, but does not compete with Ca2+, discounting fatty acid mediation of the effects of Ca2+. Neither excess Hill acceptor nor uncouplers of photophosphorylation diminish the stimulatory effects of Ca2+."} {"id": "PMID:1259962", "title": "The existence of a high photochemical turnover rate at the reaction centers of system II in Tris-washed chloroplasts.", "content": "In Tris-washed chloroplasts the kinetics of the primary electron acceptor X 320 of reaction center II has been investigated by fast repetitive flash spectroscopy with a time resolution of approximately 1 mus. It has been found that X 320 is reduced by a flash in less than or equal to 1 mus. The subsequent reoxidation in the dark occurs mainly by a reaction with a 100-200 mus kinetics. The light-induced difference spectrum confirms X 320 to be the reactive species. From these results it is concluded that in Tris-washed chloroplasts the reaction centers of System II are characterized by a high photochemical turnover rate mediated either via rapid direct charge recombination or via fast cyclic electron flow.", "contents": "The existence of a high photochemical turnover rate at the reaction centers of system II in Tris-washed chloroplasts. In Tris-washed chloroplasts the kinetics of the primary electron acceptor X 320 of reaction center II has been investigated by fast repetitive flash spectroscopy with a time resolution of approximately 1 mus. It has been found that X 320 is reduced by a flash in less than or equal to 1 mus. The subsequent reoxidation in the dark occurs mainly by a reaction with a 100-200 mus kinetics. The light-induced difference spectrum confirms X 320 to be the reactive species. From these results it is concluded that in Tris-washed chloroplasts the reaction centers of System II are characterized by a high photochemical turnover rate mediated either via rapid direct charge recombination or via fast cyclic electron flow."} {"id": "PMID:1259963", "title": "On the individuality of aliphatic and alicyclic monoester lipases in human adipose tissue.", "content": "Aliphatic and alicyclic monoester lipase activities from human adipose tissue have been comparatively investigated by using [3H] oleoylethanol and [14C] oleoylcholesterol, respectively, as substrates. A number of specific properties proved to be different for each activity. Different rates of decay of hydrolytic activity towards each substrate were observed during heat denaturation. Stability upon exposure to the cold was different for both activities, and the protective effect of glycerol was less effective for oleoylcholesterol than for oleoylethanol lipase. Serial (NH4)2SO4 fractionation in 5% increments showed that the two activities did not precipitate at identical saturation values. The behaviours of the two activities were compared in an affinity system where monoolein, a substrate molecule, served as a ligand for the enzyme(s) in a covalent complex with CH-Sepharose. During chromatography, both activities followed a comparable adsorption-elution pattern, but the oleoylcholesterol to oleoylethanol lipase activity ratio decreased by a factor of 4. Taken together, these data, along with a differential susceptibility to various surfactants, confirm our earlier hypothesis (Arnaud, J. and Boyer, J (1974) Biochim. Biophys. Acta 337, 165--168) that aliphatic and alicyclic monoester lipase activities in human fat are referable to distinct catalytic proteins.", "contents": "On the individuality of aliphatic and alicyclic monoester lipases in human adipose tissue. Aliphatic and alicyclic monoester lipase activities from human adipose tissue have been comparatively investigated by using [3H] oleoylethanol and [14C] oleoylcholesterol, respectively, as substrates. A number of specific properties proved to be different for each activity. Different rates of decay of hydrolytic activity towards each substrate were observed during heat denaturation. Stability upon exposure to the cold was different for both activities, and the protective effect of glycerol was less effective for oleoylcholesterol than for oleoylethanol lipase. Serial (NH4)2SO4 fractionation in 5% increments showed that the two activities did not precipitate at identical saturation values. The behaviours of the two activities were compared in an affinity system where monoolein, a substrate molecule, served as a ligand for the enzyme(s) in a covalent complex with CH-Sepharose. During chromatography, both activities followed a comparable adsorption-elution pattern, but the oleoylcholesterol to oleoylethanol lipase activity ratio decreased by a factor of 4. Taken together, these data, along with a differential susceptibility to various surfactants, confirm our earlier hypothesis (Arnaud, J. and Boyer, J (1974) Biochim. Biophys. Acta 337, 165--168) that aliphatic and alicyclic monoester lipase activities in human fat are referable to distinct catalytic proteins."} {"id": "PMID:1259964", "title": "Lipids and fatty acids of a moderately halophilic bacterium, No. 101.", "content": "The extractable and bound lipids of a moderately halophilic gram-negative rod, strain No. 101 (wild type) grown in a medium containing 2 M NaC1, were examined. The extractable lipids were separated into at least 8 components by using thin-layer chromatography. The major phospholipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified phosphoglycolipid in the whole cells, cell envelopes and outer membrane preparations, commonly. Judging from mild alkaline hydrolysis and exzymatic treatment with phospholipase A2, C and D, the unidentified phosphoglycolipid possessing Pi, glycerol, fatty acids and glucose in a molar ratio of 1 : 2 : 2 : 1, appeared likely to be a glucosyl derivative of phosphatidylglycerol. No glucuronic acid containing lipid was detected. The exractable lipid composition varied greatly with the concentrations of NaC1 in the medium and the stages of bacterial growth. The most characteristic phosphoglycolipid in this organism increased up to 25% of the total phospholipids with the addition of 1% glucose in the medium. The major fatty acids of the extractable lipids were C16:0, C16:1, C18:0, C18:1 and cyclopropanoic C17 and C19 acids and these compositions were very similar for each phospholipid. The cyclopropanoic fatty acids predominated as growth proceeded. The fatty acids of the bound lipids comprised a high concentration of 3-hydroxydodecanoic acid. The esterified fatty acids of the lipopolysaccharide molecule seemed to contain a wide variety of hydroxy and non-hydroxy shorter chain fatty acids, while the amide-linked fatty acids consisted almost entirely of 3-hydroxydodecanoic acid.", "contents": "Lipids and fatty acids of a moderately halophilic bacterium, No. 101. The extractable and bound lipids of a moderately halophilic gram-negative rod, strain No. 101 (wild type) grown in a medium containing 2 M NaC1, were examined. The extractable lipids were separated into at least 8 components by using thin-layer chromatography. The major phospholipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and an unidentified phosphoglycolipid in the whole cells, cell envelopes and outer membrane preparations, commonly. Judging from mild alkaline hydrolysis and exzymatic treatment with phospholipase A2, C and D, the unidentified phosphoglycolipid possessing Pi, glycerol, fatty acids and glucose in a molar ratio of 1 : 2 : 2 : 1, appeared likely to be a glucosyl derivative of phosphatidylglycerol. No glucuronic acid containing lipid was detected. The exractable lipid composition varied greatly with the concentrations of NaC1 in the medium and the stages of bacterial growth. The most characteristic phosphoglycolipid in this organism increased up to 25% of the total phospholipids with the addition of 1% glucose in the medium. The major fatty acids of the extractable lipids were C16:0, C16:1, C18:0, C18:1 and cyclopropanoic C17 and C19 acids and these compositions were very similar for each phospholipid. The cyclopropanoic fatty acids predominated as growth proceeded. The fatty acids of the bound lipids comprised a high concentration of 3-hydroxydodecanoic acid. The esterified fatty acids of the lipopolysaccharide molecule seemed to contain a wide variety of hydroxy and non-hydroxy shorter chain fatty acids, while the amide-linked fatty acids consisted almost entirely of 3-hydroxydodecanoic acid."} {"id": "PMID:1259965", "title": "Purification and partial characterization of nonspecific lipase from rat pancreas.", "content": "Nonspecific lipase (also referred to as micelle lipase and secondary ester hydrolase) has been purified to electrophoretic homogeneity starting from acetone powder of rat pancreas. The purified enzyme is found to have a molecular weight (gel filtration) of 64 000 +/- 2000, and an equivalent weight (titration with E-600) of 65 000. Nonspecific lipase is seen to be very sensitive to inhibition by organophosphates but resistant to quinine. Evidence for the presence of sulfhydryl and imidazole groups essential for activity is presented, and some observations on substrate specificity are made. The purified enzyme appears to lack phosphate groups and lipids, and is unstable under conditions of low ionic strength and/or exposure to 2-mercaptoethanol.", "contents": "Purification and partial characterization of nonspecific lipase from rat pancreas. Nonspecific lipase (also referred to as micelle lipase and secondary ester hydrolase) has been purified to electrophoretic homogeneity starting from acetone powder of rat pancreas. The purified enzyme is found to have a molecular weight (gel filtration) of 64 000 +/- 2000, and an equivalent weight (titration with E-600) of 65 000. Nonspecific lipase is seen to be very sensitive to inhibition by organophosphates but resistant to quinine. Evidence for the presence of sulfhydryl and imidazole groups essential for activity is presented, and some observations on substrate specificity are made. The purified enzyme appears to lack phosphate groups and lipids, and is unstable under conditions of low ionic strength and/or exposure to 2-mercaptoethanol."} {"id": "PMID:1259966", "title": "The thermal transitions and structural properties of 5alpha-cholestan-3beta-ol esters of aliphatic acids.", "content": "5 alpha-Cholestan-3 beta-ol esters of aliphatic acids undergo both enantiotropic and monotropic changes of state. Ten saturated and three unsaturated esters have been examined by differential scanning calorimetry and polarizing microscopy to determine transition temperatures, enthalpies, and entropies. The results are compared with an analogous series of cholesterol esters. All esters of even-numbered n-alkanoic acids from C2 to C20 melt from a crystalline state to an isotropic liquid. The crystalline state has been studied by X-ray powder diffraction. The C8 to C20 esters have progressively increasing crystalline melting transition temperatures from 76 to 99 degrees C and possess similar X-ray powder diffraction patterns, suggesting that these compounds form an isostructural series. Esters of C2, C4, and C6 acids exhibit polymorphism. Crystalline cholestanol oleate melts to an isotropic liquid, whereas cholestanol linoleate and linolenate fail to crystallize, even after several months at -20 degrees C. Esters of the even-numbered saturated acids from C4 to C14 form monotropic cholesteric liquid crystalline phases. Esters C10, C12, and C14 form smectic liquid crystalline phases. Cholestanol oleate, linoleate, and linolenate form both cholesteric and smectic mesophases. The lower smectic to cholesteric and cholesteric to isotropic transition temperatures of the cholestanol esters compared to the corresponding transition temperatures of the analogous cholesterol esters suggest that the delta 5 double bond in cholesterol increases the thermal stability of the mesophases of cholesterol esters.", "contents": "The thermal transitions and structural properties of 5alpha-cholestan-3beta-ol esters of aliphatic acids. 5 alpha-Cholestan-3 beta-ol esters of aliphatic acids undergo both enantiotropic and monotropic changes of state. Ten saturated and three unsaturated esters have been examined by differential scanning calorimetry and polarizing microscopy to determine transition temperatures, enthalpies, and entropies. The results are compared with an analogous series of cholesterol esters. All esters of even-numbered n-alkanoic acids from C2 to C20 melt from a crystalline state to an isotropic liquid. The crystalline state has been studied by X-ray powder diffraction. The C8 to C20 esters have progressively increasing crystalline melting transition temperatures from 76 to 99 degrees C and possess similar X-ray powder diffraction patterns, suggesting that these compounds form an isostructural series. Esters of C2, C4, and C6 acids exhibit polymorphism. Crystalline cholestanol oleate melts to an isotropic liquid, whereas cholestanol linoleate and linolenate fail to crystallize, even after several months at -20 degrees C. Esters of the even-numbered saturated acids from C4 to C14 form monotropic cholesteric liquid crystalline phases. Esters C10, C12, and C14 form smectic liquid crystalline phases. Cholestanol oleate, linoleate, and linolenate form both cholesteric and smectic mesophases. The lower smectic to cholesteric and cholesteric to isotropic transition temperatures of the cholestanol esters compared to the corresponding transition temperatures of the analogous cholesterol esters suggest that the delta 5 double bond in cholesterol increases the thermal stability of the mesophases of cholesterol esters."} {"id": "PMID:1259967", "title": "Direct effects of fructose metabolism on fatty acid oxidation in a recombined rat liver mitochondria-hish speed supernatant system.", "content": "The effects of fructose on the oxidation of [1-(14)C]palmitate in a rat liver mitochondria-high speed supernatant system have been investigated. This model system permitted study of the direct effects of fructose and the metabolism of fructose on fatty acid oxidation in the near absence of fatty acid esterification. Fructose inhibited the utilization of albumin-bound [1-(14)C] palmitate in the mitochondria-supernatant system, but did not affect fatty acid utilization by isolated liver mitochondria. Although fructose decreased the ATP content in the mitochondrial-supernatant system, the level of ATP throughout the incubation period was sufficient for maximal fatty acid activation. Fructose decreased the conversion of [1-(14)C]palmitate to 14CO2 and depressed the formation of total labeled oxidation products (14CO2 + 14C-labeled ketone bodies) in this system. The results suggest that fructose metabolism inhibited fatty acid oxidation in the mitochondria-supernatant system by competitive substrate oxidation and thereby decreased utilization of the added [1-(14)C]palmitate. The ihibition of L-[L-(14)C]palmitoylcarnitine oxidation, fructose was in all respects similar to its inhibition of palmitate oxidation, indicating that the site of fructose interaction was within the beta-oxidation sequence. These observations support the concept (Ontko, J.A. [1972] J. Biol. Chem. 247, 1788-1800) that the reciprocal changes in esterification and oxidation of palmitate caused by fructose in liver cells are primarily mediated via inhibitory effects on long-chain fatty acid oxidation.", "contents": "Direct effects of fructose metabolism on fatty acid oxidation in a recombined rat liver mitochondria-hish speed supernatant system. The effects of fructose on the oxidation of [1-(14)C]palmitate in a rat liver mitochondria-high speed supernatant system have been investigated. This model system permitted study of the direct effects of fructose and the metabolism of fructose on fatty acid oxidation in the near absence of fatty acid esterification. Fructose inhibited the utilization of albumin-bound [1-(14)C] palmitate in the mitochondria-supernatant system, but did not affect fatty acid utilization by isolated liver mitochondria. Although fructose decreased the ATP content in the mitochondrial-supernatant system, the level of ATP throughout the incubation period was sufficient for maximal fatty acid activation. Fructose decreased the conversion of [1-(14)C]palmitate to 14CO2 and depressed the formation of total labeled oxidation products (14CO2 + 14C-labeled ketone bodies) in this system. The results suggest that fructose metabolism inhibited fatty acid oxidation in the mitochondria-supernatant system by competitive substrate oxidation and thereby decreased utilization of the added [1-(14)C]palmitate. The ihibition of L-[L-(14)C]palmitoylcarnitine oxidation, fructose was in all respects similar to its inhibition of palmitate oxidation, indicating that the site of fructose interaction was within the beta-oxidation sequence. These observations support the concept (Ontko, J.A. [1972] J. Biol. Chem. 247, 1788-1800) that the reciprocal changes in esterification and oxidation of palmitate caused by fructose in liver cells are primarily mediated via inhibitory effects on long-chain fatty acid oxidation."} {"id": "PMID:1259968", "title": "Aliphatic chain packing in three crystalline polymorphs of a saturated racemic phosphatidylethanolamine. A quantitative electron diffraction study.", "content": "Taking advantage of the adequacy of the kinematical diffraction assumption for ab initio crystal structure analysis of long chain lipids with single crystal electron diffraction intensity data, the polymethylene chain packing in three microcrystalline polymorphs of 1,2-dipalmitoyl-rac-glycero-3-phosphoethanolamine was determined. The aliphatic chains of major crystal form pack in the new parallel/perpendicular orthorhombic methylene subcell already seen for three other compounds. The unit cell dimension s of this form are: a = 7.76 A, b = 10.03 A, c = 56.0 A. The two minor polymorphs pack in commonly-found subcells, i.e. perpendicular orthorhomibic (a(s) = 5.10 A, b(s) = 7.61 A) and hexagonal (a(s) = 4.68 A, gamma = 120 degrees). Similarities between the two orthorhombic subcells are discussed.", "contents": "Aliphatic chain packing in three crystalline polymorphs of a saturated racemic phosphatidylethanolamine. A quantitative electron diffraction study. Taking advantage of the adequacy of the kinematical diffraction assumption for ab initio crystal structure analysis of long chain lipids with single crystal electron diffraction intensity data, the polymethylene chain packing in three microcrystalline polymorphs of 1,2-dipalmitoyl-rac-glycero-3-phosphoethanolamine was determined. The aliphatic chains of major crystal form pack in the new parallel/perpendicular orthorhombic methylene subcell already seen for three other compounds. The unit cell dimension s of this form are: a = 7.76 A, b = 10.03 A, c = 56.0 A. The two minor polymorphs pack in commonly-found subcells, i.e. perpendicular orthorhomibic (a(s) = 5.10 A, b(s) = 7.61 A) and hexagonal (a(s) = 4.68 A, gamma = 120 degrees). Similarities between the two orthorhombic subcells are discussed."} {"id": "PMID:1259969", "title": "On the metabolism of prostaglandins by human gastric fundus mucosa.", "content": "1. Specific radioimmunoassays for the prostaglandins E2, F2alpha and A2 and the metabolites 13,14-dihydro-15-keto-prostaglandin E2, 15-keto-prostaglandin F2alpha and 13,14-dihydro-15-keto-prostaglandin F2alpha were used to study the metabolism of prostaglandins by gastroscopically obtained small biopsy specimens of human gastric fundus mucosa. 2. Three prostaglandin-metabolizing enzymes were found in the 100 000 X g supernatant of human gastric fundus mucosa, 15-hydroxy-prostaglandin-dehydrogenase, delta13-reductase and delta9-reductase. The specific activity was highest for 15-hydroxy-prostaglandin-dehydrogenase and lowest for delta9-reductase. 3. Formation of prostaglandin A2 (or B2) was not observed under the same conditions. 4. None of the three enzyme activities detected in the 100 000 X g supernatant was found in the 10 000 X g and 100 000 X g pellets of human gastric fundus mucosa. 5. The results indicate that high speed supernatant derived from human gastric mucosa can rapidly metabolize prostaglandin E2 and prostaglandin F2alpha to the 15-keto and 13,14-dihydro-15-keto-derivatives. Furthermore, prostaglandin E2 can be converted to prostaglandin F2alpha, the biological activity of which, on gastric functions, differs from that of prostaglandin E2.", "contents": "On the metabolism of prostaglandins by human gastric fundus mucosa. 1. Specific radioimmunoassays for the prostaglandins E2, F2alpha and A2 and the metabolites 13,14-dihydro-15-keto-prostaglandin E2, 15-keto-prostaglandin F2alpha and 13,14-dihydro-15-keto-prostaglandin F2alpha were used to study the metabolism of prostaglandins by gastroscopically obtained small biopsy specimens of human gastric fundus mucosa. 2. Three prostaglandin-metabolizing enzymes were found in the 100 000 X g supernatant of human gastric fundus mucosa, 15-hydroxy-prostaglandin-dehydrogenase, delta13-reductase and delta9-reductase. The specific activity was highest for 15-hydroxy-prostaglandin-dehydrogenase and lowest for delta9-reductase. 3. Formation of prostaglandin A2 (or B2) was not observed under the same conditions. 4. None of the three enzyme activities detected in the 100 000 X g supernatant was found in the 10 000 X g and 100 000 X g pellets of human gastric fundus mucosa. 5. The results indicate that high speed supernatant derived from human gastric mucosa can rapidly metabolize prostaglandin E2 and prostaglandin F2alpha to the 15-keto and 13,14-dihydro-15-keto-derivatives. Furthermore, prostaglandin E2 can be converted to prostaglandin F2alpha, the biological activity of which, on gastric functions, differs from that of prostaglandin E2."} {"id": "PMID:1259970", "title": "Lipolytic activity of whole isolated liver cells in aqueous suspension.", "content": "1. Liver contains a lipase which catalyzes in vitro the hydrolysis of esters of short-chain normal primary alcohols and fatty acids. It is shown that this enzymatic activity can be measured by using intact liver cells as source of enzyme. During short-term incubations of suspensions of cells isolated from rat liver, the lipase acts as a membrane-bound enzyme and readily attacks [3H] oleoylethanol added as an emulsion into the bathing medium. The lipolytic reaction proceeds linearly for at least 20 min at 37 degrees C, at the pH optimum of 8.5. [3H] Oleic acid, a reaction product, is mostly retained in the medium and is used to monitor the lipolytic process. 2. In the presence of heparin, the bound lipase is released in the medium in amounts representing one-third to one half the total activity contained in the cells. This release is very rapid and associated in all cases with a concomitant release of lactate dehydrogenase activity. Such effects are consistent with the interpretation that heparin, at concentrations comprised between 10 and 100 mug per ml, causes alterations of the plasma membrane of the isolated cells, resulting in the dispersion of membrane-bound and cytoplasmtic material. This action of heparin is totally blocked by protamine sulfate (1 mg/ml). No specific effect of heparin directed towards the selective release of lipase could be demonstrated under these conditions. 3. During incubations in the presence of heparin, it was observed that the release of monoester lipase was quantitatively related to a simultaneous decrease in membrane-bound as well as in total monoester lipase activity measureable in the cells after homogenization. This, along with the reappearance of membrane-bound activity immediately after heparin withdrawal, suggest that under the experimental conditions, the membrane-bound enzyme is replaced from inside the cell in proportion of its release by heparin.", "contents": "Lipolytic activity of whole isolated liver cells in aqueous suspension. 1. Liver contains a lipase which catalyzes in vitro the hydrolysis of esters of short-chain normal primary alcohols and fatty acids. It is shown that this enzymatic activity can be measured by using intact liver cells as source of enzyme. During short-term incubations of suspensions of cells isolated from rat liver, the lipase acts as a membrane-bound enzyme and readily attacks [3H] oleoylethanol added as an emulsion into the bathing medium. The lipolytic reaction proceeds linearly for at least 20 min at 37 degrees C, at the pH optimum of 8.5. [3H] Oleic acid, a reaction product, is mostly retained in the medium and is used to monitor the lipolytic process. 2. In the presence of heparin, the bound lipase is released in the medium in amounts representing one-third to one half the total activity contained in the cells. This release is very rapid and associated in all cases with a concomitant release of lactate dehydrogenase activity. Such effects are consistent with the interpretation that heparin, at concentrations comprised between 10 and 100 mug per ml, causes alterations of the plasma membrane of the isolated cells, resulting in the dispersion of membrane-bound and cytoplasmtic material. This action of heparin is totally blocked by protamine sulfate (1 mg/ml). No specific effect of heparin directed towards the selective release of lipase could be demonstrated under these conditions. 3. During incubations in the presence of heparin, it was observed that the release of monoester lipase was quantitatively related to a simultaneous decrease in membrane-bound as well as in total monoester lipase activity measureable in the cells after homogenization. This, along with the reappearance of membrane-bound activity immediately after heparin withdrawal, suggest that under the experimental conditions, the membrane-bound enzyme is replaced from inside the cell in proportion of its release by heparin."} {"id": "PMID:1259971", "title": "Major lipid classes in plasma membrane isolated from liver of rats fed a hepatocarcinogen.", "content": "More phosphatidylethanolamine and less phosphatidylinositol were present in the lipid of plasma membrane isolated from the liver of rats fed a diet containing the hepatocarcinogen, N-2-fluorenylacetamide than were present in the lipid of plasma membrane isolated from the liver of rats fed the basal diet. Phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin from the former membranes had relative amounts of 18 : 1 in their fatty acyl profiles that were 1.5--1.7 times the relative amount of 18 : 1 in the same phospholipid from the latter membranes. Furthermore, the former membranes contained 1.3 times more cholesterol and 1.35 times more sphingomyelin than the latter membrames.", "contents": "Major lipid classes in plasma membrane isolated from liver of rats fed a hepatocarcinogen. More phosphatidylethanolamine and less phosphatidylinositol were present in the lipid of plasma membrane isolated from the liver of rats fed a diet containing the hepatocarcinogen, N-2-fluorenylacetamide than were present in the lipid of plasma membrane isolated from the liver of rats fed the basal diet. Phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin from the former membranes had relative amounts of 18 : 1 in their fatty acyl profiles that were 1.5--1.7 times the relative amount of 18 : 1 in the same phospholipid from the latter membranes. Furthermore, the former membranes contained 1.3 times more cholesterol and 1.35 times more sphingomyelin than the latter membrames."} {"id": "PMID:1259972", "title": "Effect of mercuric and silver ions on cesium sulfate equilibrium buoyant densities of synthetic polydeoxyribonucleotides.", "content": "The effect of Hg2+ and Ag+ on the buoyant density (rho) of four synthetic DNA polymers, poly[d(A-T)]; poly(dA) - poly(dT); oikt[d(G-C)]; and poly(dG) - poly(dC), was investigated. The buoyant density of poly[d(A-T)] in Cs2SO4 increased dramatically after complexing with Hg2+, but little change in the buoyant density of other polymers resulted except at very high molar ratios of Hg2+/DNA-P (rf). Hg2+ raised the thermal transition temperature (Tm) of alternating polymers and lowered the Tm of homopolymers. Measurements in the preparative ultracentrifuge indicated that lowered Tm correlated with Hg2+-induced strand separation of one homopolymer [poly(dA) - poly(dT)], but strand separation was not observed with another homopolymer [poly(dG) - poly(dC)] complexed with Hg2+. When Ag+ was mixed with the polymers, the buoyant density of poly(dG) - poly(dC) increased most markedly. A substantial increase in the buoyant density of poly[d(A-T)] and a small increase in the buoyant density of poly[d(G-C)] were also observed. The Tm changes induced by Ag+ were not related in any obvious way to buoyant density changes. These findings indicate that nucleotide sequence as well as overall base composition is of importance in understanding the buoyant density changes induced by metal ions. Although these data do not allow construction of a detailed molecular model of polymer-metal ion interactions, they may be used to explain much of the behavior of naturally occurring DNA sequences, such as heterochromatic satellite sequences and 5 S and rRNA sequences, in Hg2+/Cs2SO4 and Ag+/Cs2SO4 gradients.", "contents": "Effect of mercuric and silver ions on cesium sulfate equilibrium buoyant densities of synthetic polydeoxyribonucleotides. The effect of Hg2+ and Ag+ on the buoyant density (rho) of four synthetic DNA polymers, poly[d(A-T)]; poly(dA) - poly(dT); oikt[d(G-C)]; and poly(dG) - poly(dC), was investigated. The buoyant density of poly[d(A-T)] in Cs2SO4 increased dramatically after complexing with Hg2+, but little change in the buoyant density of other polymers resulted except at very high molar ratios of Hg2+/DNA-P (rf). Hg2+ raised the thermal transition temperature (Tm) of alternating polymers and lowered the Tm of homopolymers. Measurements in the preparative ultracentrifuge indicated that lowered Tm correlated with Hg2+-induced strand separation of one homopolymer [poly(dA) - poly(dT)], but strand separation was not observed with another homopolymer [poly(dG) - poly(dC)] complexed with Hg2+. When Ag+ was mixed with the polymers, the buoyant density of poly(dG) - poly(dC) increased most markedly. A substantial increase in the buoyant density of poly[d(A-T)] and a small increase in the buoyant density of poly[d(G-C)] were also observed. The Tm changes induced by Ag+ were not related in any obvious way to buoyant density changes. These findings indicate that nucleotide sequence as well as overall base composition is of importance in understanding the buoyant density changes induced by metal ions. Although these data do not allow construction of a detailed molecular model of polymer-metal ion interactions, they may be used to explain much of the behavior of naturally occurring DNA sequences, such as heterochromatic satellite sequences and 5 S and rRNA sequences, in Hg2+/Cs2SO4 and Ag+/Cs2SO4 gradients."} {"id": "PMID:1259974", "title": "Nuclear ribonucleoproteins as inhibitors of mammalian RNA polymerase.", "content": "A ribonucleoprotein complex isolated from rabbit thymus nuclear lysates was found to be an inhibitor of DNA-dependent RNA polymerase II. The inhibition appeared to be of a competitive type and was completely reversed by high concentration of DNA. Highest inhibition was observed when enzyme and complex were preincubated before addition of DNA while there was little inhibition after enzyme had started synthesis on the DNA template. The RNA isolated from the complex was equally inhibitory and was a more effective inhibitor than either tRNA or rRNA.", "contents": "Nuclear ribonucleoproteins as inhibitors of mammalian RNA polymerase. A ribonucleoprotein complex isolated from rabbit thymus nuclear lysates was found to be an inhibitor of DNA-dependent RNA polymerase II. The inhibition appeared to be of a competitive type and was completely reversed by high concentration of DNA. Highest inhibition was observed when enzyme and complex were preincubated before addition of DNA while there was little inhibition after enzyme had started synthesis on the DNA template. The RNA isolated from the complex was equally inhibitory and was a more effective inhibitor than either tRNA or rRNA."} {"id": "PMID:1259975", "title": "Nuclear magnetic relaxation studies of cytidine and its complexing dimethyl sulfoxide solution.", "content": "13C spin-lattice relazation times (T1 values) in cytidine were determined experimentally to investigate molecular motions of both metal-free and ion-complexed cytidines in dimethylsulfoxide solutions. It was found that the correlation times of the protonated carbons were equal within experimental error, and this equality of correlation times of different sites of the molecule suggests strongly isotropic random motion of the molecule. Correlation times for internal motion of the amino group obtained from the observed T1 of the amino protons are 4.6 -10(-11) S, 2.0 - 10(-9) S and 1.1 - 10(-10) S for the metal-free cytidine and the cytidine complexed with either CaCl2 or ZnCl2, respectively. An experimental value of T1 of the H6 proton of the cytidine base agrees very well with the value estimated from a conformation determined by the nuclear \"Overhauser\" effect. Spin-lattice relaxation time measurements of the 7Li nucleus in the LiCl/cytidine system strongly suggested that the 7Li cation is directly coordinated with cytidine.", "contents": "Nuclear magnetic relaxation studies of cytidine and its complexing dimethyl sulfoxide solution. 13C spin-lattice relazation times (T1 values) in cytidine were determined experimentally to investigate molecular motions of both metal-free and ion-complexed cytidines in dimethylsulfoxide solutions. It was found that the correlation times of the protonated carbons were equal within experimental error, and this equality of correlation times of different sites of the molecule suggests strongly isotropic random motion of the molecule. Correlation times for internal motion of the amino group obtained from the observed T1 of the amino protons are 4.6 -10(-11) S, 2.0 - 10(-9) S and 1.1 - 10(-10) S for the metal-free cytidine and the cytidine complexed with either CaCl2 or ZnCl2, respectively. An experimental value of T1 of the H6 proton of the cytidine base agrees very well with the value estimated from a conformation determined by the nuclear \"Overhauser\" effect. Spin-lattice relaxation time measurements of the 7Li nucleus in the LiCl/cytidine system strongly suggested that the 7Li cation is directly coordinated with cytidine."} {"id": "PMID:1259977", "title": "Comparison of proteins bound to the different functional classes of messenger RNA.", "content": "Proteins from nuclear ribonucleoproteins, informosomes, polysomal messenger ribonucleoproteins and cytoplasmic \"binding factor\" are characterized. 1. Nuclear ribonucleoproteins are purified from nuclei disrupted by ultrasonication. Possible contamination by nucleoplasm, histones or remaining cytoplasmic structures is controlled. 2. Informosomal proteins are obtained by mild RNAase degradation. This method gives informosomal proteins without appreciable contamination. 3. Polysomal messenger ribonucleoproteins are obtained from cells where the initiation of protein synthesis is arrested in order to release the messenger ribonucleoproteins from the polysomes. Their proteins are obtained like the informosomal proteins by mild RNAase digestion. No contamination by informosomes could be detected by sodium dodecyl sulfate gel electrophoresis. 4. Cytoplasmic \"binding factor\" proteins are purified by affinity chromatography. 5. The four sets of proteins are analysed by sodium dodecylsulfate acrylamide gel electrophoresis. In spite of the fact that some proteins from one or another kind of messenger ribonucleoprotein, have apparently the same molecular weight, the majority of proteins differ.", "contents": "Comparison of proteins bound to the different functional classes of messenger RNA. Proteins from nuclear ribonucleoproteins, informosomes, polysomal messenger ribonucleoproteins and cytoplasmic \"binding factor\" are characterized. 1. Nuclear ribonucleoproteins are purified from nuclei disrupted by ultrasonication. Possible contamination by nucleoplasm, histones or remaining cytoplasmic structures is controlled. 2. Informosomal proteins are obtained by mild RNAase degradation. This method gives informosomal proteins without appreciable contamination. 3. Polysomal messenger ribonucleoproteins are obtained from cells where the initiation of protein synthesis is arrested in order to release the messenger ribonucleoproteins from the polysomes. Their proteins are obtained like the informosomal proteins by mild RNAase digestion. No contamination by informosomes could be detected by sodium dodecyl sulfate gel electrophoresis. 4. Cytoplasmic \"binding factor\" proteins are purified by affinity chromatography. 5. The four sets of proteins are analysed by sodium dodecylsulfate acrylamide gel electrophoresis. In spite of the fact that some proteins from one or another kind of messenger ribonucleoprotein, have apparently the same molecular weight, the majority of proteins differ."} {"id": "PMID:1259978", "title": "Physical aspects and cytoplasmic distribution of messenger RNA in mouse kidney.", "content": "As a prerequisite to examining mRNA metabolism in compensatory renal hypertrophy, polyadenylated RNA has been purified from normal mouse kidney polysomal RNA by selection on oligo(dT)-cellulose. Poly(A)-containing RNA dissociated from polysomes by treatment with 10 mM EDTA and sedimented heterogeneously in dodecyl sulfate-containing sucrose density gradients with a mean sedimentation coefficient of 20 S. Poly(A) derived from this RNA migrated at the rate of 6-7 S RNA in dodecyl sulfate-containing 10% polyacrylamide gels. Coelectrophoresis of poly(A) labeled for 90 min with poly(A) labeled for 24 h indicated the long-term labeled poly(A) migrated faster than pulse-labeled material. Twenty percent of the cytoplasmic poly(A)-containing mRNA was not associated with the polysomes, but sedimented in the 40-80 S region (post-polysomal). Messenger RNA from the post-polysomal region had sedimentation properties similar to those of mRNA prepared from polysomes indicating post-polysomal mRNA was not degraded polysomal mRNA. Preliminary labeling experiments indicated a rapid equilibration of radioactivity between the polysomal and post-polysomal mRNA populations, suggesting the post-polysomal mRNA may consist of mRNA in transit to the polysomes.", "contents": "Physical aspects and cytoplasmic distribution of messenger RNA in mouse kidney. As a prerequisite to examining mRNA metabolism in compensatory renal hypertrophy, polyadenylated RNA has been purified from normal mouse kidney polysomal RNA by selection on oligo(dT)-cellulose. Poly(A)-containing RNA dissociated from polysomes by treatment with 10 mM EDTA and sedimented heterogeneously in dodecyl sulfate-containing sucrose density gradients with a mean sedimentation coefficient of 20 S. Poly(A) derived from this RNA migrated at the rate of 6-7 S RNA in dodecyl sulfate-containing 10% polyacrylamide gels. Coelectrophoresis of poly(A) labeled for 90 min with poly(A) labeled for 24 h indicated the long-term labeled poly(A) migrated faster than pulse-labeled material. Twenty percent of the cytoplasmic poly(A)-containing mRNA was not associated with the polysomes, but sedimented in the 40-80 S region (post-polysomal). Messenger RNA from the post-polysomal region had sedimentation properties similar to those of mRNA prepared from polysomes indicating post-polysomal mRNA was not degraded polysomal mRNA. Preliminary labeling experiments indicated a rapid equilibration of radioactivity between the polysomal and post-polysomal mRNA populations, suggesting the post-polysomal mRNA may consist of mRNA in transit to the polysomes."} {"id": "PMID:1259979", "title": "Effects of irradiation on RNA synthesis primed by calf thymus deoxyribonucleoprotein treated with salt and salt-urea.", "content": "1. The effects of ionizing radiation on the activity of calf thymus templates were examined in a Escherichia coli RNA polymerase system. 2. The template activity of native and 2 M NaCl-5M urea-treated deoxyribonucleoproteins was enhanced by relatively low doses of irradiation, while that of 2 M NaCl-treated deoxyribonucleoprotein was not enhanced by irradiation. 3. The template activity of purified DNA was markedly decreased by irradiation, while that of native deoxyribonucleoprotein, 2 M NaCl-treated, and 2 M NaCl-5 M urea-treated ones were slightly decreased at a higher dose range. The doses for 50% inactivation of these templates were 1.3, 210, 140, and approximately 200 krad, respectively.", "contents": "Effects of irradiation on RNA synthesis primed by calf thymus deoxyribonucleoprotein treated with salt and salt-urea. 1. The effects of ionizing radiation on the activity of calf thymus templates were examined in a Escherichia coli RNA polymerase system. 2. The template activity of native and 2 M NaCl-5M urea-treated deoxyribonucleoproteins was enhanced by relatively low doses of irradiation, while that of 2 M NaCl-treated deoxyribonucleoprotein was not enhanced by irradiation. 3. The template activity of purified DNA was markedly decreased by irradiation, while that of native deoxyribonucleoprotein, 2 M NaCl-treated, and 2 M NaCl-5 M urea-treated ones were slightly decreased at a higher dose range. The doses for 50% inactivation of these templates were 1.3, 210, 140, and approximately 200 krad, respectively."} {"id": "PMID:1259980", "title": "Processing of ribosomal RNA in a temperature sensitive mutant of BHK cells.", "content": "The processing of ribosomal RNA has been studied in a temperature sensitive mutant of the Syrian hamster cell line BHK 21. At 39 degrees C, these cells are unable to synthesize 28S RNA, and 60S ribosomal subunits, while 18S RNA, and 40S subunits are produced at both temperatures. At 39 degrees C the 45S RNA precursor is transcribed and processed as in wild type cells. The processing of the RNA precursors becomes defective after the cleavage of the 41S RNA, and the separation of the 18S and 28S RNAs sequences in two different RNA molecules. The 36S RNA precursor, which is always present in very small quantity in the nucleoli of wild type cells and of the mutant at 33 degrees C, is found in very large amounts in the mutant at 39 degrees C. The 36S RNA can be, however, slowly processed to 32S RNA. The 32S RNA cannot be processed at 39 degrees C, and it is degraded soon after its formation. Only a small proportion accumulates in the nucleoli. The 32S RNA synthesized at 39 degrees C cannot be processed to 28S RNA upon shift to the permissive temperature, even when the processing of the newly synthesized rRNA has returned to normal. The data suggest that the 36S and 32S RNAs are contained in aberrant ribonucleoprotein particles, leading to a defective processing of the particles as a whole.", "contents": "Processing of ribosomal RNA in a temperature sensitive mutant of BHK cells. The processing of ribosomal RNA has been studied in a temperature sensitive mutant of the Syrian hamster cell line BHK 21. At 39 degrees C, these cells are unable to synthesize 28S RNA, and 60S ribosomal subunits, while 18S RNA, and 40S subunits are produced at both temperatures. At 39 degrees C the 45S RNA precursor is transcribed and processed as in wild type cells. The processing of the RNA precursors becomes defective after the cleavage of the 41S RNA, and the separation of the 18S and 28S RNAs sequences in two different RNA molecules. The 36S RNA precursor, which is always present in very small quantity in the nucleoli of wild type cells and of the mutant at 33 degrees C, is found in very large amounts in the mutant at 39 degrees C. The 36S RNA can be, however, slowly processed to 32S RNA. The 32S RNA cannot be processed at 39 degrees C, and it is degraded soon after its formation. Only a small proportion accumulates in the nucleoli. The 32S RNA synthesized at 39 degrees C cannot be processed to 28S RNA upon shift to the permissive temperature, even when the processing of the newly synthesized rRNA has returned to normal. The data suggest that the 36S and 32S RNAs are contained in aberrant ribonucleoprotein particles, leading to a defective processing of the particles as a whole."} {"id": "PMID:1259981", "title": "T4-endonuclease V-sensitive sites in DNA from ultraviolet-irradiated human cells.", "content": "Human diploid cells (WI38) were pre-labeled with 32Pi, exposed to ultraviolet irradiation and then pulse labeled with [3H]thymidine. The extracted DNA from these cells was subsequently treated with the T4-endonuclease V, an enzyme which specifically nicks DNA strands at positions adjacent to pyrimidine dimers. Sedimentation in alkaline sucrose gradients revealed that the DNA synthesized after irradiation, as well as that made before, contained endonuclease-sensitive sites. Our results suggest that pyrimidine dimers are transferred from parental to daughter DNA strands during post-irradiation incubation. Sedimentation in neutral sucrose gradients showed that the molecular weight of native DNA was not affected by the endonuclease treatment, suggesting that the gaps appearing in daughter strands after irradiation are not opposite dimers or that the enzyme cannot recognize dimers in the gap regions.", "contents": "T4-endonuclease V-sensitive sites in DNA from ultraviolet-irradiated human cells. Human diploid cells (WI38) were pre-labeled with 32Pi, exposed to ultraviolet irradiation and then pulse labeled with [3H]thymidine. The extracted DNA from these cells was subsequently treated with the T4-endonuclease V, an enzyme which specifically nicks DNA strands at positions adjacent to pyrimidine dimers. Sedimentation in alkaline sucrose gradients revealed that the DNA synthesized after irradiation, as well as that made before, contained endonuclease-sensitive sites. Our results suggest that pyrimidine dimers are transferred from parental to daughter DNA strands during post-irradiation incubation. Sedimentation in neutral sucrose gradients showed that the molecular weight of native DNA was not affected by the endonuclease treatment, suggesting that the gaps appearing in daughter strands after irradiation are not opposite dimers or that the enzyme cannot recognize dimers in the gap regions."} {"id": "PMID:1259982", "title": "DNA polymerase, thymidine kinase and DNA synthesis in erythropoietic mouse spleen cells separated on bovine serum albumin gradients.", "content": "A single dose of erythropoietin stimulates DNA synthesis in the spleen of the polycythemic mouse with the maximum effect occurring 48 h after the hormone is administered. The increase in DNA synthesis is accompanied by morphologic evidence of increased erythropoiesis and by increases in the activities per cell of both thymidine kinase and cytoplasmic high molecular weight DNA polymerase-alpha. The activity of low molecular weight DNA polymerase-beta does not change significantly. Spleen cells from mice which had received either erythropoietin or saline 48 h previously were separated into 7 density classes on discontinuous bovine serum albumin gradients. Following the administration of erythropoietin, thymidine incorporation and thymidine kinase activity showed the greatest relative increases per nucleated cell in layers 3, 4 and 5 of the gradient. DNA polymerase-alpha showed the greatest increase in cells of the denser layers 5, 6 and 7. Each layer contained normoblasts and lymphocytes. The less well differentiated erythroid elements constituted a larger proportion of cells in layers of lower density. Increases in the rates of thymidine incorporation were better correlated with increases in thymidine kinase activity than with increases in DNA polymerase activities. Measurement of iron incorporation into heme confirm the morphological impression that the cell type responsible for increased thymidine incorporation and increased DNA polymerase-alpha activity is the young normblast.", "contents": "DNA polymerase, thymidine kinase and DNA synthesis in erythropoietic mouse spleen cells separated on bovine serum albumin gradients. A single dose of erythropoietin stimulates DNA synthesis in the spleen of the polycythemic mouse with the maximum effect occurring 48 h after the hormone is administered. The increase in DNA synthesis is accompanied by morphologic evidence of increased erythropoiesis and by increases in the activities per cell of both thymidine kinase and cytoplasmic high molecular weight DNA polymerase-alpha. The activity of low molecular weight DNA polymerase-beta does not change significantly. Spleen cells from mice which had received either erythropoietin or saline 48 h previously were separated into 7 density classes on discontinuous bovine serum albumin gradients. Following the administration of erythropoietin, thymidine incorporation and thymidine kinase activity showed the greatest relative increases per nucleated cell in layers 3, 4 and 5 of the gradient. DNA polymerase-alpha showed the greatest increase in cells of the denser layers 5, 6 and 7. Each layer contained normoblasts and lymphocytes. The less well differentiated erythroid elements constituted a larger proportion of cells in layers of lower density. Increases in the rates of thymidine incorporation were better correlated with increases in thymidine kinase activity than with increases in DNA polymerase activities. Measurement of iron incorporation into heme confirm the morphological impression that the cell type responsible for increased thymidine incorporation and increased DNA polymerase-alpha activity is the young normblast."} {"id": "PMID:1259983", "title": "Comparison of turnover rates of proteins of the brain, liver and kidney in mouse in vivo following long term labeling.", "content": "Intraperitoneal injection of [14C]tyrosine suspension followed by subcutaneous implantation of a [14C]tyrosine pellet in mice produced a fairly constant specific activity of plasma free tyrosine for 5 days, and for 3-5 days in the tissue free amino acid pool. The specific activity of tyrosine in the tissue (brain, liver, and kidney) free amino acid pool was 75-90% of that in plasma. Incorporation of tyrosine into tissue proteins was followed for 5 days in brain; during this time 33% of tissue proteins were labeled. Incorporation for 68 h in liver and kidney showed labeling of over 70% of the protein of these tissues. These percentages assume a homogeneous tissue free tyrosine pool as the precursor. The rate of incorporation initially was 0.6, 2.8, and 2.0% per h in brain, liver, and kidney protein, respectively. These rates decreased in longer term experiments. The best fit to the incorporation curves was obtained by assuming the following average half-lives for tissue proteins: brain, two compartments, 5.7% with a half-life of 15 h, 94.3% with a half-life of 10 days; liver, a single compartment with a 26-h half-life; kidney, two compartments, 41% with an 18-h half-life, and 59% with a 63-h half-life.", "contents": "Comparison of turnover rates of proteins of the brain, liver and kidney in mouse in vivo following long term labeling. Intraperitoneal injection of [14C]tyrosine suspension followed by subcutaneous implantation of a [14C]tyrosine pellet in mice produced a fairly constant specific activity of plasma free tyrosine for 5 days, and for 3-5 days in the tissue free amino acid pool. The specific activity of tyrosine in the tissue (brain, liver, and kidney) free amino acid pool was 75-90% of that in plasma. Incorporation of tyrosine into tissue proteins was followed for 5 days in brain; during this time 33% of tissue proteins were labeled. Incorporation for 68 h in liver and kidney showed labeling of over 70% of the protein of these tissues. These percentages assume a homogeneous tissue free tyrosine pool as the precursor. The rate of incorporation initially was 0.6, 2.8, and 2.0% per h in brain, liver, and kidney protein, respectively. These rates decreased in longer term experiments. The best fit to the incorporation curves was obtained by assuming the following average half-lives for tissue proteins: brain, two compartments, 5.7% with a half-life of 15 h, 94.3% with a half-life of 10 days; liver, a single compartment with a 26-h half-life; kidney, two compartments, 41% with an 18-h half-life, and 59% with a 63-h half-life."} {"id": "PMID:1259984", "title": "Phenylalanine uptake in isolated renal brush border vesicles.", "content": "The uptake of L-phenylalanine into brush border microvilli vesicles and basolateral plasma membrane vesicles isolated from rat kidney cortex by differential centrifugation and free flow electrophoresis was investigated using filtration techniques. Brush border microvilli but not basolateral plasma membrane vesicles take up L-phenylalanine by an Na+-dependent, saturable transport system. The apparent affinity of the transport system for L-phenylalanine is 6.1 mM at 100 mM Na+ and for Na+ 13mM at 1 mM L-phenylalanine. Reduction of the Na+ concentration reduces the apparent affinity of the transport system for L-phenylalanine but does not alter the maximum velocity. In the presence of an electrochemical potential difference of Na+ across the membrane (etaNao greater than etaNai) the brush border microvilli accumulate transiently L-phenylalanine over the concentration in the incubation medium (overshoot pheomenon). This overshoot and the initial rate of uptake are markedly increased when the intravesicular space is rendered electrically more negative by membrane diffusion potentials induced by the use of highly permeant anions, of valinomycin in the presence of an outwardly directed K+ gradient and of carbonyl cyanide p-trifluoromethoxyphenylhydrazone in the presence of an outward-directed proton gradient. These results indicate that the entry of L-phenylalanine across the brush border membrane into the proximal tubular epithelial cells involves cotransport with Na+ and is dependent on the concentration difference of the amino acid, on the concentration difference of Na+ and on the electrical potential difference. The exit of L-phenylalanine across the basolateral plasma membranes is Na+-independent and probably involves facilitated diffusion.", "contents": "Phenylalanine uptake in isolated renal brush border vesicles. The uptake of L-phenylalanine into brush border microvilli vesicles and basolateral plasma membrane vesicles isolated from rat kidney cortex by differential centrifugation and free flow electrophoresis was investigated using filtration techniques. Brush border microvilli but not basolateral plasma membrane vesicles take up L-phenylalanine by an Na+-dependent, saturable transport system. The apparent affinity of the transport system for L-phenylalanine is 6.1 mM at 100 mM Na+ and for Na+ 13mM at 1 mM L-phenylalanine. Reduction of the Na+ concentration reduces the apparent affinity of the transport system for L-phenylalanine but does not alter the maximum velocity. In the presence of an electrochemical potential difference of Na+ across the membrane (etaNao greater than etaNai) the brush border microvilli accumulate transiently L-phenylalanine over the concentration in the incubation medium (overshoot pheomenon). This overshoot and the initial rate of uptake are markedly increased when the intravesicular space is rendered electrically more negative by membrane diffusion potentials induced by the use of highly permeant anions, of valinomycin in the presence of an outwardly directed K+ gradient and of carbonyl cyanide p-trifluoromethoxyphenylhydrazone in the presence of an outward-directed proton gradient. These results indicate that the entry of L-phenylalanine across the brush border membrane into the proximal tubular epithelial cells involves cotransport with Na+ and is dependent on the concentration difference of the amino acid, on the concentration difference of Na+ and on the electrical potential difference. The exit of L-phenylalanine across the basolateral plasma membranes is Na+-independent and probably involves facilitated diffusion."} {"id": "PMID:1259985", "title": "Effect of melittin on thermotropic lipid state transitions in phosphatidylcholine liposomes.", "content": "We have examined the Raman scattering due to CH stretching vibrations, as well as to v(-C=C-) and v(=C-C=) of beta-carotene, of liposomes composed of phosphatidylcholine (egg, dimyristoyl, dipalmitoyl) +/- cholesterol, beta-carotene or melittin in the temperature range of -10 degrees C to 45 degrees C. (2) Plots vs. temperature of the intensities of the 2885 cm-1 and 2930 cm-1 CH stretching bands relative to the intensity of the thermally stable 2850 cm-1 band, i.e. the I2885/I2850 and I2930/I2850 ratios, reveal a sharp discontinuity in cholesterol-free phosphatidylcholine liposomes; this coincides with the gel leads to liquid-crystal transition temperature of the fatty acyl chains. In cholesterol/phosphatudylcholine liposomes the change in I2885/I2850 occurs over a very broad temperature range and I2930/I2850 remains stable. (3) I1527/I1158, i.e. the intensity of v(-C=C-) relative to that of v(=C-C-) in beta-carotene/phosphatidylcholine liposomes, changes discontinuously at the gel leads to liquid-crystal transition temperature. The values above the transition temperature approach those of the carotenoid in organic solution. (4) The transitions reported in I2885/I2850 for phosphatidylcholine/melittin liposomes (25-56; 1, M/M) are shifted to much higher temperatures than observed in phosphatidylcholine liposomes. In the case of dimyristoyl phosphatidylcholine/melittin the changes in I2930/I2850 also occurs at a higher temperature (28 degrees C) than without melittin (21 degrees C), but the temperature shift is less than the +13 degrees C observed for I2885/I2850. It appears that the apolar moiety of melittin organizes phospholipids adjacent to and more remote from the peptide moiety, to form complexes with an elevated lipid transition temperature. The effect of the peptide moiety is greater on the methylene segments (I2885/I2850) than on the methyl termini (I2930/I2850).", "contents": "Effect of melittin on thermotropic lipid state transitions in phosphatidylcholine liposomes. We have examined the Raman scattering due to CH stretching vibrations, as well as to v(-C=C-) and v(=C-C=) of beta-carotene, of liposomes composed of phosphatidylcholine (egg, dimyristoyl, dipalmitoyl) +/- cholesterol, beta-carotene or melittin in the temperature range of -10 degrees C to 45 degrees C. (2) Plots vs. temperature of the intensities of the 2885 cm-1 and 2930 cm-1 CH stretching bands relative to the intensity of the thermally stable 2850 cm-1 band, i.e. the I2885/I2850 and I2930/I2850 ratios, reveal a sharp discontinuity in cholesterol-free phosphatidylcholine liposomes; this coincides with the gel leads to liquid-crystal transition temperature of the fatty acyl chains. In cholesterol/phosphatudylcholine liposomes the change in I2885/I2850 occurs over a very broad temperature range and I2930/I2850 remains stable. (3) I1527/I1158, i.e. the intensity of v(-C=C-) relative to that of v(=C-C-) in beta-carotene/phosphatidylcholine liposomes, changes discontinuously at the gel leads to liquid-crystal transition temperature. The values above the transition temperature approach those of the carotenoid in organic solution. (4) The transitions reported in I2885/I2850 for phosphatidylcholine/melittin liposomes (25-56; 1, M/M) are shifted to much higher temperatures than observed in phosphatidylcholine liposomes. In the case of dimyristoyl phosphatidylcholine/melittin the changes in I2930/I2850 also occurs at a higher temperature (28 degrees C) than without melittin (21 degrees C), but the temperature shift is less than the +13 degrees C observed for I2885/I2850. It appears that the apolar moiety of melittin organizes phospholipids adjacent to and more remote from the peptide moiety, to form complexes with an elevated lipid transition temperature. The effect of the peptide moiety is greater on the methylene segments (I2885/I2850) than on the methyl termini (I2930/I2850)."} {"id": "PMID:1259986", "title": "Stacking of safranine in liposomes during valinomycin-induced efflux of potassium ions.", "content": "Liposomes were prepared from phosphatidylcholine and cardiolipin in a KCl medium and suspended in a choline chloride medium with safranine. When efflux of K+ was induced by valinomycin, spectral shifts characteristic of stacking were observed. Ca2+ inhibited the rate of stacking in a competitive manner with a Ki of about 200 muM, while La3+ was about 10 times more potent. When liposomes were prepared from phospholipids with a higher ratio of cardiolipin to phosphatidylcholine the inhibition was more potent. No effect on the stacking phenomena was seen when CA2+ was added after the stacking was completed. When CA2+ or an organic cation with four charges, spermine was trapped in the intraliposomal compartment, no significant change in the rate of stacking was seen. However, the extent of stacking was decreased. It is suggested that safranine is driven by a diffusion potential to a site that is inaccessible to CA2+ in the medium, presumably to the inner boundaries of the liposomal membranes.", "contents": "Stacking of safranine in liposomes during valinomycin-induced efflux of potassium ions. Liposomes were prepared from phosphatidylcholine and cardiolipin in a KCl medium and suspended in a choline chloride medium with safranine. When efflux of K+ was induced by valinomycin, spectral shifts characteristic of stacking were observed. Ca2+ inhibited the rate of stacking in a competitive manner with a Ki of about 200 muM, while La3+ was about 10 times more potent. When liposomes were prepared from phospholipids with a higher ratio of cardiolipin to phosphatidylcholine the inhibition was more potent. No effect on the stacking phenomena was seen when CA2+ was added after the stacking was completed. When CA2+ or an organic cation with four charges, spermine was trapped in the intraliposomal compartment, no significant change in the rate of stacking was seen. However, the extent of stacking was decreased. It is suggested that safranine is driven by a diffusion potential to a site that is inaccessible to CA2+ in the medium, presumably to the inner boundaries of the liposomal membranes."} {"id": "PMID:1259987", "title": "Molecular changes in cell surface membranes resulting from trypsinization of sarcoma 180 tumor cells.", "content": "Sarcoma-180 tumor cells in culture or grown as an ascites form in the CD-1 mouse have been subjected to mild trypsinization procedures in order to study morphological and molecular changes resulting from proteolysis. The cells attached to a substratum become rounded within 20 min. and most undergo cell division, but they do not detach from the substratum. Removal of trypsin permits the cells to go back to their original spindle shape over an 8-20 h period. Surface membranes were isolated from trypsinized ascites and cultured cells and subjected to dodecyl sulfate-acrylamide gel electrophoresis. Both cell types showed the same two kinds of changes in electrophoretic patterns. First, there was a loss of glycoproteins from both cell types even though they show different complements of cell surface glycoproteins. Second, there is a loss of high molecular weight polypeptides, which have previously been suggested to play a role in membrane stabilization and cell shape. These results further implicate these polypeptides in the control of cell morphology and offer circumstanital evidence for transmembrane interactions of surface glycoproteins with the high molecular weight polypeptides as a factor in controlling cell morphology.", "contents": "Molecular changes in cell surface membranes resulting from trypsinization of sarcoma 180 tumor cells. Sarcoma-180 tumor cells in culture or grown as an ascites form in the CD-1 mouse have been subjected to mild trypsinization procedures in order to study morphological and molecular changes resulting from proteolysis. The cells attached to a substratum become rounded within 20 min. and most undergo cell division, but they do not detach from the substratum. Removal of trypsin permits the cells to go back to their original spindle shape over an 8-20 h period. Surface membranes were isolated from trypsinized ascites and cultured cells and subjected to dodecyl sulfate-acrylamide gel electrophoresis. Both cell types showed the same two kinds of changes in electrophoretic patterns. First, there was a loss of glycoproteins from both cell types even though they show different complements of cell surface glycoproteins. Second, there is a loss of high molecular weight polypeptides, which have previously been suggested to play a role in membrane stabilization and cell shape. These results further implicate these polypeptides in the control of cell morphology and offer circumstanital evidence for transmembrane interactions of surface glycoproteins with the high molecular weight polypeptides as a factor in controlling cell morphology."} {"id": "PMID:1259988", "title": "Study of water permeability through phospholipid vesicle membranes by 17O NMR.", "content": "Vesicle suspensions of up to 5% egg lecithin and 2.5% cholesterol have been found to have no effect on the NMR relaxation times of 17O from water. Addition of 1-5 mM Mn2+ to an equimolar vesicle suspension of egg lecithin and cholesterol permitted resolution of the free induction decay into two exponential components, a fast one arising from the external water and a slow one arising from the intravesicular fluid. From the rates of relaxation the mean life time of the water molecules within the vesicles was calculated to be 1+/- 0.1 ms at 22 degrees C. The size of the vesicle was estimated from electron micrographs to be about 500 A in diameter. These data yield an equilibrium water permeability, Pw, of about 8 mus-1 for the vesicle membranes. From the temperature dependence of Pw an activation energy of 12+/-2 kcal/mol was obtained. The longitudinal relaxation time (T1) of water within vesicles remained the same as in pure water.", "contents": "Study of water permeability through phospholipid vesicle membranes by 17O NMR. Vesicle suspensions of up to 5% egg lecithin and 2.5% cholesterol have been found to have no effect on the NMR relaxation times of 17O from water. Addition of 1-5 mM Mn2+ to an equimolar vesicle suspension of egg lecithin and cholesterol permitted resolution of the free induction decay into two exponential components, a fast one arising from the external water and a slow one arising from the intravesicular fluid. From the rates of relaxation the mean life time of the water molecules within the vesicles was calculated to be 1+/- 0.1 ms at 22 degrees C. The size of the vesicle was estimated from electron micrographs to be about 500 A in diameter. These data yield an equilibrium water permeability, Pw, of about 8 mus-1 for the vesicle membranes. From the temperature dependence of Pw an activation energy of 12+/-2 kcal/mol was obtained. The longitudinal relaxation time (T1) of water within vesicles remained the same as in pure water."} {"id": "PMID:1259989", "title": "Effect of maleic acid on the kinetics of alpha-methyl-D-glucoside uptake by isolated rat renal tubules.", "content": "ALPHA-Methyl-D-glucoside has been used to study the invitro mechanism of the effect of maleic acid on sugar transport, using isolated rat renal tubule fragments. 6 mM maleate maximally inhibits the ability of the tubule to establish a concentration gradient for this model sugar with no evidence of ultrastructural changes. This inhibition is due to a 100% increase in efflux, as well as to a 50% decrease in influx with more prolonged incubation. The data presented here are consistent with those of other workers, but their work does not explain our results, which therefore deserve further investigation by other techniques.", "contents": "Effect of maleic acid on the kinetics of alpha-methyl-D-glucoside uptake by isolated rat renal tubules. ALPHA-Methyl-D-glucoside has been used to study the invitro mechanism of the effect of maleic acid on sugar transport, using isolated rat renal tubule fragments. 6 mM maleate maximally inhibits the ability of the tubule to establish a concentration gradient for this model sugar with no evidence of ultrastructural changes. This inhibition is due to a 100% increase in efflux, as well as to a 50% decrease in influx with more prolonged incubation. The data presented here are consistent with those of other workers, but their work does not explain our results, which therefore deserve further investigation by other techniques."} {"id": "PMID:1259990", "title": "Modification of the fatty acid composition of Ehrlich ascites tumor cell plasma membranes.", "content": "The fatty acyl group composition of Ehrlich ascites tumor cell plasma membranes was modified by feeding the tumor-bearing mice diets rich in either coconut or sunflower oil. When coconut oil was fed, the oleate content of the membrane phospholipids was elevated and the linoleate content reduced. The opposite occurred when sunflower oil was fed. Qualitatively similar changes were observed in the plasma membrane phosphatidylethanolamine, phosphatidylcholine and mixed phosphatidylserine plus phosphatidylinositol fractions. These diets also produced differences in the sphingomyelin fraction, particularly in the palmitic and nervonic acid contents. Unexpectedly, the saturated fatty acid content of the plasma membrane phospholipids was somewhat greater when the highly polyunsaturated sunflower oil was fed. The small quantities of neutral lipids contained in the plasma membrane exhibited changes in acyl group composition similar to those observed in the phospholipids. These fatty acyl group changes were not accompanied by any alteration in the cholesterol or phospholipid contents of the plasma membranes. Therefore, the lipid alterations produced in this experimental model system are confined to the membrane acyl groups.", "contents": "Modification of the fatty acid composition of Ehrlich ascites tumor cell plasma membranes. The fatty acyl group composition of Ehrlich ascites tumor cell plasma membranes was modified by feeding the tumor-bearing mice diets rich in either coconut or sunflower oil. When coconut oil was fed, the oleate content of the membrane phospholipids was elevated and the linoleate content reduced. The opposite occurred when sunflower oil was fed. Qualitatively similar changes were observed in the plasma membrane phosphatidylethanolamine, phosphatidylcholine and mixed phosphatidylserine plus phosphatidylinositol fractions. These diets also produced differences in the sphingomyelin fraction, particularly in the palmitic and nervonic acid contents. Unexpectedly, the saturated fatty acid content of the plasma membrane phospholipids was somewhat greater when the highly polyunsaturated sunflower oil was fed. The small quantities of neutral lipids contained in the plasma membrane exhibited changes in acyl group composition similar to those observed in the phospholipids. These fatty acyl group changes were not accompanied by any alteration in the cholesterol or phospholipid contents of the plasma membranes. Therefore, the lipid alterations produced in this experimental model system are confined to the membrane acyl groups."} {"id": "PMID:1259992", "title": "Interactions of neomycin and calcium in synaptosomal membranes and polyphosphoinostide monolayers.", "content": "Neomycin and related aminoglycosidic antibiotics displace calcium from synaptosomes of guinea pig cerebral cortex and from preparations of phosphatidylinositol diphosphate. At low drug concentrations, inhibition of synaptosomal calcium binding is competitive (Ki = 3-10(-5) M), at high concentrations it is non-competitive (Ki = 4-10(-4) M). Monomolecular films of phosphatidylinositol diphosphate are contracted by low concentrations of neomycin in the subphase, and are expanded at high concentrations. This expansion perists even at the collapse pressure indicating a strong interaction between the drug and the lipid.", "contents": "Interactions of neomycin and calcium in synaptosomal membranes and polyphosphoinostide monolayers. Neomycin and related aminoglycosidic antibiotics displace calcium from synaptosomes of guinea pig cerebral cortex and from preparations of phosphatidylinositol diphosphate. At low drug concentrations, inhibition of synaptosomal calcium binding is competitive (Ki = 3-10(-5) M), at high concentrations it is non-competitive (Ki = 4-10(-4) M). Monomolecular films of phosphatidylinositol diphosphate are contracted by low concentrations of neomycin in the subphase, and are expanded at high concentrations. This expansion perists even at the collapse pressure indicating a strong interaction between the drug and the lipid."} {"id": "PMID:1259993", "title": "Primary sequence of the beta-chain of Badger haemoglobin.", "content": "Badger (Meles meles) haemoglobin was purified by paper electrophoresis and converted into globin. Chain separation was carried out on a CM-cellulose column in the presence of 8 M urea. The beta-chain was aminoethylated, purified by gel filtration and submitted to tryptic digestion. A fingerprint obtained with the enzymic digests showed 17 distinct ninhydrin-positive spots from which 20 pure peptides were isolated by further electrochromatographic separations. These peptides were sequenced using Dansyl-Edman and Ptc-Edman degradation techniques. The presence of amide residues was confirmed after aminopeptidase M hydrolysis. Taking human haemoglobin beta-chain as a model, the covalent structure could be completely resolved without the help of any further overlapping technique. The following substitutions were noted (badger/human, position): Ala/Pro5, Ser/Ala13, Tyr/Phe41, Asp/Glu43, Ser/Ala70, Glu/Asp73, Lys/Ala76, Asn/His77, Lys/Thr87, Lys/Arg104 and Gln/Pro125. A comparison with other haemoglobin beta-chains already sequenced shows a greater similarity with dog haemoglobin, the only example of beta-chain of known structure in the order of Carnivores.", "contents": "Primary sequence of the beta-chain of Badger haemoglobin. Badger (Meles meles) haemoglobin was purified by paper electrophoresis and converted into globin. Chain separation was carried out on a CM-cellulose column in the presence of 8 M urea. The beta-chain was aminoethylated, purified by gel filtration and submitted to tryptic digestion. A fingerprint obtained with the enzymic digests showed 17 distinct ninhydrin-positive spots from which 20 pure peptides were isolated by further electrochromatographic separations. These peptides were sequenced using Dansyl-Edman and Ptc-Edman degradation techniques. The presence of amide residues was confirmed after aminopeptidase M hydrolysis. Taking human haemoglobin beta-chain as a model, the covalent structure could be completely resolved without the help of any further overlapping technique. The following substitutions were noted (badger/human, position): Ala/Pro5, Ser/Ala13, Tyr/Phe41, Asp/Glu43, Ser/Ala70, Glu/Asp73, Lys/Ala76, Asn/His77, Lys/Thr87, Lys/Arg104 and Gln/Pro125. A comparison with other haemoglobin beta-chains already sequenced shows a greater similarity with dog haemoglobin, the only example of beta-chain of known structure in the order of Carnivores."} {"id": "PMID:1259994", "title": "Two new haemoglobins: haemoglobin Perspolis (alpha 64 (E13) Asp leads to Tyr) and haemoglobin J-Kurosh (alpha 19 (AB) Ala leads to Asp).", "content": "Two new haemoglobins are described which were found during a regular survey on voluntary blood donors in Iran. They are haemoglobin Perspolis [alpha 64 (E13) Asp leads to Tyr] and haemoglobin J-Kurosh [alpha 19 (AB) Ala leads to Asp]. The amino acid substitution in these two variants was determined by fingerprinting and amino acid analysis of the tryptic peptides and thermolytic peptides derived from abnormal tryptic peptides. Neither haemoglobin was associated with clinical symptoms.", "contents": "Two new haemoglobins: haemoglobin Perspolis (alpha 64 (E13) Asp leads to Tyr) and haemoglobin J-Kurosh (alpha 19 (AB) Ala leads to Asp). Two new haemoglobins are described which were found during a regular survey on voluntary blood donors in Iran. They are haemoglobin Perspolis [alpha 64 (E13) Asp leads to Tyr] and haemoglobin J-Kurosh [alpha 19 (AB) Ala leads to Asp]. The amino acid substitution in these two variants was determined by fingerprinting and amino acid analysis of the tryptic peptides and thermolytic peptides derived from abnormal tryptic peptides. Neither haemoglobin was associated with clinical symptoms."} {"id": "PMID:1259995", "title": "Structure and morphogenesis of photosynthetic membranes. I. Is there a single basic peptide within Zea mays thylakoids?", "content": "We have previously given evidence for a physical heterogeneity among proteins from photosynthetic membranes of maize chloroplast [1]. About fifteen components have now been identified, differing in their molecular weights and also in their varying abilities to bind protochlorophyllide and chlorophyll [2]. In this paper, we show that all these proteins have very similar amino acid compositions. A detailed chemical comparison is made between, on one hand the mixture of all proteins and on the other the smallest component of molecular weight 10 000. All the features analysed (percent of non-proteic material, partial peptide maps, N and Cterminal ends and content of linked sugars) are the same in both cases. We conclude from these experiments that it is likely that all components are generated with the same basic peptide unit. This assertion seems to be confirmed by the fact that, after mild alkaline treatment, all the components are converted into the smallest one, as seen by electrophoresis. Thus, within the photosynthesizing membranes, there appears to be a basic structural protein unit, present in a form that is more or less \"polymerized\". This may account for most of the particular, and sometimes disturbing, properties so far described for this system. It is likely that such a peptide, or a similar one, would provide a framework for all photosynthesizing structures.", "contents": "Structure and morphogenesis of photosynthetic membranes. I. Is there a single basic peptide within Zea mays thylakoids? We have previously given evidence for a physical heterogeneity among proteins from photosynthetic membranes of maize chloroplast [1]. About fifteen components have now been identified, differing in their molecular weights and also in their varying abilities to bind protochlorophyllide and chlorophyll [2]. In this paper, we show that all these proteins have very similar amino acid compositions. A detailed chemical comparison is made between, on one hand the mixture of all proteins and on the other the smallest component of molecular weight 10 000. All the features analysed (percent of non-proteic material, partial peptide maps, N and Cterminal ends and content of linked sugars) are the same in both cases. We conclude from these experiments that it is likely that all components are generated with the same basic peptide unit. This assertion seems to be confirmed by the fact that, after mild alkaline treatment, all the components are converted into the smallest one, as seen by electrophoresis. Thus, within the photosynthesizing membranes, there appears to be a basic structural protein unit, present in a form that is more or less \"polymerized\". This may account for most of the particular, and sometimes disturbing, properties so far described for this system. It is likely that such a peptide, or a similar one, would provide a framework for all photosynthesizing structures."} {"id": "PMID:1259996", "title": "The application of acetylated Sephadex for the separation of proteolipids.", "content": "The finding that acetylated Sephadex G 200 swells in chloroform/methanol mixture and still acts as a molecular sieve has permitted for the first time the separation of several proteolipid fractions from brain white matter, two of which appear almost free of phospholipids. This new procedure will be useful not only for a rapid purification of proteolipids and separation of lipids but also for general purposes of protein chemistry in organic media. However, it is predictable that one of the main uses of the method will be in the isolation of membrane carrier and of cholinergic receptor proteins, since these components appear to be of proteolipid(-like) nature.", "contents": "The application of acetylated Sephadex for the separation of proteolipids. The finding that acetylated Sephadex G 200 swells in chloroform/methanol mixture and still acts as a molecular sieve has permitted for the first time the separation of several proteolipid fractions from brain white matter, two of which appear almost free of phospholipids. This new procedure will be useful not only for a rapid purification of proteolipids and separation of lipids but also for general purposes of protein chemistry in organic media. However, it is predictable that one of the main uses of the method will be in the isolation of membrane carrier and of cholinergic receptor proteins, since these components appear to be of proteolipid(-like) nature."} {"id": "PMID:1259997", "title": "Further resolution of adult chick hemoglobins by isoelectric focusing in polyacrylamide gel.", "content": "Evidence is presented that adult chick hemoglobins exist in four types separable by isoelectric focusing on polyacrylamide gels instead of the two hemoglobin types previously resolved by other methods. These are hemoglobin A1 (HbA1), hemoglobin A2 (HbA2), hemoglobin D1 (HbD1), and hemoglobin D2(HbD2). Their pI values are 7.53 +/- 0.02, 7.37 +/- 0.02, 6.92 +/- 0.04 and 6.72 +/- 0.05, respectively, constituting about 63, 14, 18 and 5% of the total hemoglobin from adult chick erythrocytes, respectively. HbA1 and HbA2 ar identical in size, as determined on sodium dodecyl sulfate gels and similar in their amino acid composition and tryptic peptides. The molecular weight and amino acid composition of HbD1 and HbD2 are also identical although there are differences in their tryptic peptides. Experiments were done to show that the existence of four hemoglobin types is not due to genetic heterogeneity of the experimental animal, nor to artifacts of oxidation of carboxyhemoglobin to methemoglobin tetramers. Care was exercised to eliminate deamination and modification of side chain amino groups by using freshly prepared hemolysates and to minimize the \"plateau phenomenon\" peculiar to isoelectric focusing by controlling the duration of electrophoresis. The use of cyanmet form of (thus liganded) hemoglobin in this study reduced the chance of heterotetramer formation. Furthermore, consideration was given to possible anomalies caused by ampholytes. In the face of negative evidence for artifacts, it is concluded that adult chicken has more than the two hemoglobin types previously reported.", "contents": "Further resolution of adult chick hemoglobins by isoelectric focusing in polyacrylamide gel. Evidence is presented that adult chick hemoglobins exist in four types separable by isoelectric focusing on polyacrylamide gels instead of the two hemoglobin types previously resolved by other methods. These are hemoglobin A1 (HbA1), hemoglobin A2 (HbA2), hemoglobin D1 (HbD1), and hemoglobin D2(HbD2). Their pI values are 7.53 +/- 0.02, 7.37 +/- 0.02, 6.92 +/- 0.04 and 6.72 +/- 0.05, respectively, constituting about 63, 14, 18 and 5% of the total hemoglobin from adult chick erythrocytes, respectively. HbA1 and HbA2 ar identical in size, as determined on sodium dodecyl sulfate gels and similar in their amino acid composition and tryptic peptides. The molecular weight and amino acid composition of HbD1 and HbD2 are also identical although there are differences in their tryptic peptides. Experiments were done to show that the existence of four hemoglobin types is not due to genetic heterogeneity of the experimental animal, nor to artifacts of oxidation of carboxyhemoglobin to methemoglobin tetramers. Care was exercised to eliminate deamination and modification of side chain amino groups by using freshly prepared hemolysates and to minimize the \"plateau phenomenon\" peculiar to isoelectric focusing by controlling the duration of electrophoresis. The use of cyanmet form of (thus liganded) hemoglobin in this study reduced the chance of heterotetramer formation. Furthermore, consideration was given to possible anomalies caused by ampholytes. In the face of negative evidence for artifacts, it is concluded that adult chicken has more than the two hemoglobin types previously reported."} {"id": "PMID:1259998", "title": "Polymerization of protamine sulphate by carbodiimide and interaction of isolated protamine polymers with human red blood cells.", "content": "A method using a water-soluble carbodiimide to polymerize protamine sulphate is described. The behaviour of polymerized protamine in Sephadex chromatography and in polyacrylamide gel electrophoresis indicates that protamine has been polymerized into aggregates with defined molecular weights. Turbidimetrical titrations of the isolated protamine polymers with dextran sulphate show that the cationic charge density has been conserved after polymerization. The binding characteristics of the protamine polymers to human red blood cells as measured by cell electrophoresis indicate increased affinity with increased molecular weight of the polymer.", "contents": "Polymerization of protamine sulphate by carbodiimide and interaction of isolated protamine polymers with human red blood cells. A method using a water-soluble carbodiimide to polymerize protamine sulphate is described. The behaviour of polymerized protamine in Sephadex chromatography and in polyacrylamide gel electrophoresis indicates that protamine has been polymerized into aggregates with defined molecular weights. Turbidimetrical titrations of the isolated protamine polymers with dextran sulphate show that the cationic charge density has been conserved after polymerization. The binding characteristics of the protamine polymers to human red blood cells as measured by cell electrophoresis indicate increased affinity with increased molecular weight of the polymer."} {"id": "PMID:1259999", "title": "Estimation of the Stokes radii of serum proteins for a study of protein movement from blood to amniotic fluid.", "content": "The effective hydrodynamic (Stokes) radii of fifteen serum proteins were estimated by Sephadex G 200 gel filtration and immunochemical methods. The Waldmann-Meyer and Birch equation (Protides Biol. Fluids, Proc. 21st Colloq. (1974) (Peeters, H., ed.), Vol. 21, pp. 653-656, Pergamon Press, Oxford) was used for maximum accuracy. Three replicate column runs were made to assess the precision for the size determinations (coefficients of variation 0.6-2.7(). Quantive two-dimensional immunoelectrophoresis was used to measure eleven proteins in specimens of serum and amniotic fluid collected from twelve normal pregnancies. There was a close inverse linear relationship between the amniotic fluid/serum ratios of the proteins and their Stokes radii. This indicates that the movement of a protein from the blood to amniotic fluid is determined by the size of the protein. The linear correlation of protein amniotic fluid/serum ratio with Stokes radius was better than that with molecular weight. This demonstrates that, as an expression of protein size, Stokes radius should be used in preference to molecular weight when protein filtration systems are being investigated.", "contents": "Estimation of the Stokes radii of serum proteins for a study of protein movement from blood to amniotic fluid. The effective hydrodynamic (Stokes) radii of fifteen serum proteins were estimated by Sephadex G 200 gel filtration and immunochemical methods. The Waldmann-Meyer and Birch equation (Protides Biol. Fluids, Proc. 21st Colloq. (1974) (Peeters, H., ed.), Vol. 21, pp. 653-656, Pergamon Press, Oxford) was used for maximum accuracy. Three replicate column runs were made to assess the precision for the size determinations (coefficients of variation 0.6-2.7(). Quantive two-dimensional immunoelectrophoresis was used to measure eleven proteins in specimens of serum and amniotic fluid collected from twelve normal pregnancies. There was a close inverse linear relationship between the amniotic fluid/serum ratios of the proteins and their Stokes radii. This indicates that the movement of a protein from the blood to amniotic fluid is determined by the size of the protein. The linear correlation of protein amniotic fluid/serum ratio with Stokes radius was better than that with molecular weight. This demonstrates that, as an expression of protein size, Stokes radius should be used in preference to molecular weight when protein filtration systems are being investigated."} {"id": "PMID:1260000", "title": "Experimental allergic aspermatogenic orchitis. II. Some chemical properties of the AP1 protein of the sperm acrosome.", "content": "The AP1 protein, a unique aspermatogenic protein localized in the sperm acrosome, exists as a single polypeptide chain of 136 amino acids, as shown by a single band on gel electrophoresis in sodium dodecyl sulfate and the recovery of the expected 21 to 22 tryptic peptides on peptide mapping. The AP1 protein appears to exist in a compact, highly stable conformation, as shown by its resistance to trypsin hydrolysis. Its aspermatogenic acitivity is not affected by trypsin treatment, by heating at 99 degrees C for 1 h, by 8 M urea, or by acid conditions. After reduction and alkylation, however, the molecule appears to open up, since it becomes hydrolyzable by trypsin and migrates more slowly on gel electrophoresis at pH 2.7 and 8.6. After alkylation, the AP1 protein still migrates as a single band at pH 2.7. The AP1 protein shows microheterogeneity near its isolectric point at pH 8.6; each of five bands shows the same amino acid analysis. Aggregation was not observed following treatment with dimethylsuberimidate. The molecular weight of 15 000, obtained from gel electrophoresis consists of 136 amino acids with a relatively high content of proline, half cystine, glycine, histidine and tryptophan. No galactose, mannose, fucose, glucose, or hexosamines were found; the AP1 protein is thus not a glycoprotein.", "contents": "Experimental allergic aspermatogenic orchitis. II. Some chemical properties of the AP1 protein of the sperm acrosome. The AP1 protein, a unique aspermatogenic protein localized in the sperm acrosome, exists as a single polypeptide chain of 136 amino acids, as shown by a single band on gel electrophoresis in sodium dodecyl sulfate and the recovery of the expected 21 to 22 tryptic peptides on peptide mapping. The AP1 protein appears to exist in a compact, highly stable conformation, as shown by its resistance to trypsin hydrolysis. Its aspermatogenic acitivity is not affected by trypsin treatment, by heating at 99 degrees C for 1 h, by 8 M urea, or by acid conditions. After reduction and alkylation, however, the molecule appears to open up, since it becomes hydrolyzable by trypsin and migrates more slowly on gel electrophoresis at pH 2.7 and 8.6. After alkylation, the AP1 protein still migrates as a single band at pH 2.7. The AP1 protein shows microheterogeneity near its isolectric point at pH 8.6; each of five bands shows the same amino acid analysis. Aggregation was not observed following treatment with dimethylsuberimidate. The molecular weight of 15 000, obtained from gel electrophoresis consists of 136 amino acids with a relatively high content of proline, half cystine, glycine, histidine and tryptophan. No galactose, mannose, fucose, glucose, or hexosamines were found; the AP1 protein is thus not a glycoprotein."} {"id": "PMID:1260001", "title": "Purification and some properties of the phosphoprotein from rat incisors.", "content": "The phosphoprotein of rat incisors has been purified by successive gel and ion-exchange chromatography. The product gave a single band on polyacrylamide gel electrophoresis and contained approximately 34% phosphoserine and 32% aspartic acid. Alkaline elimination experiments showed all the phosphate to be present as phosphoserine. Ultraviolet spectra in the presence or absence of ATP showed that the phosphoprotein did not contain an nucleotide moiety as suggested by Veis, A., Spector, A. R. and Zamoscianyk, H. ((1972) Biochim. Biophys. Acta 257, 404-413) for bovine dentin phosphoprotein.", "contents": "Purification and some properties of the phosphoprotein from rat incisors. The phosphoprotein of rat incisors has been purified by successive gel and ion-exchange chromatography. The product gave a single band on polyacrylamide gel electrophoresis and contained approximately 34% phosphoserine and 32% aspartic acid. Alkaline elimination experiments showed all the phosphate to be present as phosphoserine. Ultraviolet spectra in the presence or absence of ATP showed that the phosphoprotein did not contain an nucleotide moiety as suggested by Veis, A., Spector, A. R. and Zamoscianyk, H. ((1972) Biochim. Biophys. Acta 257, 404-413) for bovine dentin phosphoprotein."} {"id": "PMID:1260002", "title": "Infrared magnetic circular dichroism of myoglobin derivatives.", "content": "By use of a newly constructed CD instrument, infrared magnetic circular dichroism (MCD) spectra were observed for various myoglobin derivatives. The ferric high spin myoglobin derivatives such as fluoride, water and hydroxide complexes, commonly exhibited the MCD spectra consisting of positive A terms. Therefore, the results reinforced the assignment that the infrared band is the charge transfer transition to the degenerate excited state (eg (dpi)). Since the fraction of A term estimated was approximately 80% for myoglobin fluoride and approximately 35% for myoglobin water, the effective symmetry for myoglobin fluoride is determined to be as close as D4h, while that for myoglobin water seems to have lower symmetry components. The ferric low spin derivatives such as myoglobin cyanide, myoglobin imidazole and myoglobin azide showed positive MCD spectra which are very similar to the electronic absorption spectra. These MCD spectra were assigned to the charge transfer transitions from porphyrin pi to iron d orbitals on the ground that they were observed only for the ferric low spin groups and insensitive to the axial ligands. The lack of temperature dependence in the MCD magnitude indicated that the MCD spectra are attributable to the Faraday B terms. Deoxymyoglobin, the ferrous high spin derivative, had fairly strong positive MCD around 760 nm with an anisotropy factor (delta epsilon/epsilon) of 1.4-10(-4). It shows some small MCD bands from 800 to 1800 nm. Among the ferrous low spin derivatives, carbonmonoxymyoglobin did not give any observable MCD in the infrared region while oxymyoglobin seemed to have significant MCD in the range from 700 to 1000 nm.", "contents": "Infrared magnetic circular dichroism of myoglobin derivatives. By use of a newly constructed CD instrument, infrared magnetic circular dichroism (MCD) spectra were observed for various myoglobin derivatives. The ferric high spin myoglobin derivatives such as fluoride, water and hydroxide complexes, commonly exhibited the MCD spectra consisting of positive A terms. Therefore, the results reinforced the assignment that the infrared band is the charge transfer transition to the degenerate excited state (eg (dpi)). Since the fraction of A term estimated was approximately 80% for myoglobin fluoride and approximately 35% for myoglobin water, the effective symmetry for myoglobin fluoride is determined to be as close as D4h, while that for myoglobin water seems to have lower symmetry components. The ferric low spin derivatives such as myoglobin cyanide, myoglobin imidazole and myoglobin azide showed positive MCD spectra which are very similar to the electronic absorption spectra. These MCD spectra were assigned to the charge transfer transitions from porphyrin pi to iron d orbitals on the ground that they were observed only for the ferric low spin groups and insensitive to the axial ligands. The lack of temperature dependence in the MCD magnitude indicated that the MCD spectra are attributable to the Faraday B terms. Deoxymyoglobin, the ferrous high spin derivative, had fairly strong positive MCD around 760 nm with an anisotropy factor (delta epsilon/epsilon) of 1.4-10(-4). It shows some small MCD bands from 800 to 1800 nm. Among the ferrous low spin derivatives, carbonmonoxymyoglobin did not give any observable MCD in the infrared region while oxymyoglobin seemed to have significant MCD in the range from 700 to 1000 nm."} {"id": "PMID:1260003", "title": "Thermal denaturation and photochemistry of bacteriorhodopsin from Halobacterium cutirubrum as monitored by resonance Raman spectroscopy.", "content": "Resonance Raman studies of the thermal denaturation of bacteriorhodopsin from Halobacterium cutirubrum show that the N-retinylidenelysine moiety present in the chromophore is N-protonated. This corroborates an earlier suggestion of Lewis et al. ((1974) Proc. Natl. Acad. Sci. U.S., 71, 4462-4466). The widely differing excitation profiles of two -C=C- stretching modes are explained in terms of the light-initiated reaction cycle in the molecule. Glutaraldehyde fixation of bacteriorhodopsin has no effect on the intensity ratio of the two modes, suggesting that no large motion of the protein is necessary for the photoreaction cycle to occur.", "contents": "Thermal denaturation and photochemistry of bacteriorhodopsin from Halobacterium cutirubrum as monitored by resonance Raman spectroscopy. Resonance Raman studies of the thermal denaturation of bacteriorhodopsin from Halobacterium cutirubrum show that the N-retinylidenelysine moiety present in the chromophore is N-protonated. This corroborates an earlier suggestion of Lewis et al. ((1974) Proc. Natl. Acad. Sci. U.S., 71, 4462-4466). The widely differing excitation profiles of two -C=C- stretching modes are explained in terms of the light-initiated reaction cycle in the molecule. Glutaraldehyde fixation of bacteriorhodopsin has no effect on the intensity ratio of the two modes, suggesting that no large motion of the protein is necessary for the photoreaction cycle to occur."} {"id": "PMID:1260004", "title": "The interaction of collagen with alpha1-acid glycoprotein.", "content": "The influence of alpha1-acid glycoprotein on the formation of fibrous long spacing fibers of collagen has been investigated. It was observed that addition of the glycoprotein to dialyzed collagen solutions caused a significant decrease in the intensity of the circular dichroic spectrum of collagen. This phenomenon, which displays an optimum with respect to glycoprotein, is consistent with previous observations of fibrous long spacing fiber formation. Changes in viscosity of collagen initially dissolved in acetic acid were monitored during dialysis. It was found that a significant increase in viscosity must occur during dialysis of collagen before fibrous long spacing formation could take place. This increase in viscosity can be related directly to removal of acetic acid from the collagen solution. Removal of all sialyl residues from the alpha1-acid glycoprotein with neuraminidase prevents fibrous long spacing formation while removal of up to 35% of the sialyl residues has no effect on the interaction of glycoprotein with collagen. Amino acid composition and radioactivity studies suggest that 45-55% of the insoluble fibrous long spacing fibers is glycoprotein. In contrast to native collagen fibers, reduced fibrous long spacing fibers do not contain histidinohydroxymerodesmosine or hydroxylysinonorleucine. Instead, they contain significant quantities of allysine aldol and epsilon-hydroxynorleucine.", "contents": "The interaction of collagen with alpha1-acid glycoprotein. The influence of alpha1-acid glycoprotein on the formation of fibrous long spacing fibers of collagen has been investigated. It was observed that addition of the glycoprotein to dialyzed collagen solutions caused a significant decrease in the intensity of the circular dichroic spectrum of collagen. This phenomenon, which displays an optimum with respect to glycoprotein, is consistent with previous observations of fibrous long spacing fiber formation. Changes in viscosity of collagen initially dissolved in acetic acid were monitored during dialysis. It was found that a significant increase in viscosity must occur during dialysis of collagen before fibrous long spacing formation could take place. This increase in viscosity can be related directly to removal of acetic acid from the collagen solution. Removal of all sialyl residues from the alpha1-acid glycoprotein with neuraminidase prevents fibrous long spacing formation while removal of up to 35% of the sialyl residues has no effect on the interaction of glycoprotein with collagen. Amino acid composition and radioactivity studies suggest that 45-55% of the insoluble fibrous long spacing fibers is glycoprotein. In contrast to native collagen fibers, reduced fibrous long spacing fibers do not contain histidinohydroxymerodesmosine or hydroxylysinonorleucine. Instead, they contain significant quantities of allysine aldol and epsilon-hydroxynorleucine."} {"id": "PMID:1260005", "title": "Isolation of peptides containing citrulline and the cross-link, epsilon-(gamma-glutamyl)lysine, from hair medulla protein.", "content": "The epsilon-(gamma-glutamyl)lysine cross-link has been unequivocally localized in the citrulline-containing protein of hair medulla tissue. This was achieved by the isolation of cross-linked peptides that contain citrulline. The peptides were purified by molecular sieving, cation-exchange and paper chromatography and paper electrophoresis and their amino acid compositions are reported. They were detected by analyzing a large number obtained from a tryptic digest of thermolytic peptides of the medulla protein. There is no evidence at present as to whether the cross-link is in fact inter- or intrachain, or both.", "contents": "Isolation of peptides containing citrulline and the cross-link, epsilon-(gamma-glutamyl)lysine, from hair medulla protein. The epsilon-(gamma-glutamyl)lysine cross-link has been unequivocally localized in the citrulline-containing protein of hair medulla tissue. This was achieved by the isolation of cross-linked peptides that contain citrulline. The peptides were purified by molecular sieving, cation-exchange and paper chromatography and paper electrophoresis and their amino acid compositions are reported. They were detected by analyzing a large number obtained from a tryptic digest of thermolytic peptides of the medulla protein. There is no evidence at present as to whether the cross-link is in fact inter- or intrachain, or both."} {"id": "PMID:1260006", "title": "The paradoxical effect of fatty acid on steroid-albumin interaction.", "content": "Careful investigation of the influence of palmitic and lauric acid on the interaction of progesterone and testosterone with several batches of untreated and defatted bovine and human serum albumins have revealed that, by contrast with published data for studies with progesterone as well as nonsteroid ligands, there is a surprising stimulation rather than inhibition of binding, albeit with a reduction of the apparent number of binding sites in almost all instances. Furthermore, fatty acid tends to minimize or eliminate the well-known differences in affinity between bovine and human albumin for interactions with these two steroids. The values for binding affinity in the interaction of testosterone with these batches of human serum albumin are significantly higher than those previously published by us and other authors and the value for progesterone-bovine albumin interaction is not in accordance with the \"polarity rule\". Studies of these same interactions by ultraviolet difference spectroscopy give further evidence of the augmentation in binding but, in the case of defatted bovine albumin only, the aromatic difference troughs are indicative of tyrosine perturbation whereas refatted bovine albumin, defatted and refatted human albumin manifest tryptophan perturbation. Quantitative correlation of perturbation with level of bound steroid suggests that fatty acid alters the ratio (possibly hydrogen-bonded to non hydrogen-bonded) of two forms of bound steroid. There is also further evidence that the binding sites for testosterone and progesterone are not identical.", "contents": "The paradoxical effect of fatty acid on steroid-albumin interaction. Careful investigation of the influence of palmitic and lauric acid on the interaction of progesterone and testosterone with several batches of untreated and defatted bovine and human serum albumins have revealed that, by contrast with published data for studies with progesterone as well as nonsteroid ligands, there is a surprising stimulation rather than inhibition of binding, albeit with a reduction of the apparent number of binding sites in almost all instances. Furthermore, fatty acid tends to minimize or eliminate the well-known differences in affinity between bovine and human albumin for interactions with these two steroids. The values for binding affinity in the interaction of testosterone with these batches of human serum albumin are significantly higher than those previously published by us and other authors and the value for progesterone-bovine albumin interaction is not in accordance with the \"polarity rule\". Studies of these same interactions by ultraviolet difference spectroscopy give further evidence of the augmentation in binding but, in the case of defatted bovine albumin only, the aromatic difference troughs are indicative of tyrosine perturbation whereas refatted bovine albumin, defatted and refatted human albumin manifest tryptophan perturbation. Quantitative correlation of perturbation with level of bound steroid suggests that fatty acid alters the ratio (possibly hydrogen-bonded to non hydrogen-bonded) of two forms of bound steroid. There is also further evidence that the binding sites for testosterone and progesterone are not identical."} {"id": "PMID:1260007", "title": "A comparative study of the thermal denaturation parameters of lysozyme in the dissolved and crystalline states.", "content": "Differential scanning calorimetry was used for investigating the conformational changes of lysozyme resulting from the combined actions of temperature and of denaturants at various concentrations. The transition temperatures, for the protein in the dissolved and in the crystalline states (tetragonal crystals, crosslinked by glutaraldehyde), were thus investigated in a variety of environmental conditions. The effect of a wide range of alcohols demonstrates that lysozyme, whether in solution or crystalline, displays structural features which are on the whole strikingly similar. By contrast, in the case of urea this similarity becomes apparent only for concentrations higher than 4 M. Molecular interpretation of the data, as discussed in the text, is entirely consistent with information from X-ray studies.", "contents": "A comparative study of the thermal denaturation parameters of lysozyme in the dissolved and crystalline states. Differential scanning calorimetry was used for investigating the conformational changes of lysozyme resulting from the combined actions of temperature and of denaturants at various concentrations. The transition temperatures, for the protein in the dissolved and in the crystalline states (tetragonal crystals, crosslinked by glutaraldehyde), were thus investigated in a variety of environmental conditions. The effect of a wide range of alcohols demonstrates that lysozyme, whether in solution or crystalline, displays structural features which are on the whole strikingly similar. By contrast, in the case of urea this similarity becomes apparent only for concentrations higher than 4 M. Molecular interpretation of the data, as discussed in the text, is entirely consistent with information from X-ray studies."} {"id": "PMID:1260008", "title": "Surface activity of hemoglobin S and other human hemoglobin variants.", "content": "The kinetics of surface pressure change (deltapi vs. t isotherms) were determined for several single point mutations of the human hemoglobin system. It was observed that hemoglobin S and hemoglobin CHarlem (both containing beta6 Glu leads to Val substitutions) have a specific behavior at the water-air interface: their extent of surface pressure change is larger than for hemoglobin A, hemoglobin C and hemoglobin Korle Bu (beta73 Asp leads to Asn). In addition, hemoglobin S seems to occupy a larger area per molecule than hemoglobin A. The conformational requirements for this property, in addition to the beta6 Val substitution, appear to be the liganded state of the betas chain in the tetramer. Electrostatic, hydrogen bonding and hydrophobic interactions are involved in determining the surface activity of a hemoglobin molecule. The differences between the surface activity of oxyhemoglobin S and oxyhemoglobin A could be the basis for their differences in mechanical precipitability, although other factors may play a role.", "contents": "Surface activity of hemoglobin S and other human hemoglobin variants. The kinetics of surface pressure change (deltapi vs. t isotherms) were determined for several single point mutations of the human hemoglobin system. It was observed that hemoglobin S and hemoglobin CHarlem (both containing beta6 Glu leads to Val substitutions) have a specific behavior at the water-air interface: their extent of surface pressure change is larger than for hemoglobin A, hemoglobin C and hemoglobin Korle Bu (beta73 Asp leads to Asn). In addition, hemoglobin S seems to occupy a larger area per molecule than hemoglobin A. The conformational requirements for this property, in addition to the beta6 Val substitution, appear to be the liganded state of the betas chain in the tetramer. Electrostatic, hydrogen bonding and hydrophobic interactions are involved in determining the surface activity of a hemoglobin molecule. The differences between the surface activity of oxyhemoglobin S and oxyhemoglobin A could be the basis for their differences in mechanical precipitability, although other factors may play a role."} {"id": "PMID:1260009", "title": "Origin of Nicotiana tabacum detected by primary structure of fraction I protein.", "content": "Nicotiana tabacum is believed to have arisen after hybridization of Nicotiana sylvestris with a species in the Tomentosae section of the genus Nicotiana. Recent biochemical experiments have confirmed the conclusions from previous cytogenetic studies that N. sylvestris was the maternal parent and have indicated that Nicotiana tomentosiformis was the paternal parent. However, these studies did not take into account the possibility that a new species of Nicotiana, called K-12, discovered in South America in 1968, could also have been one of the parents. Fraction I proteins were purified from N. tabacum and its putative progenitors, and separated into large and small subunits. Chymotryptic peptides of each subunit were analyzed by ion exchange column chromatography with a gradient elution system. Among 38 resolved peaks of the large subunits, 2 peaks were found to be different among the putative species. Since only N. sylvestris showed an identical chromatogram with N. tabacum, N. sylvestris was concluded to be the maternal progenitor, as the genetic information for the large subunit of Fraction I protein was known to be inherited by the cytoplasmic mode. On the other hand, the small subunit of Fraction I protein is inherited by the Mendelian mode and therefore N. tabacum, an allopolyploid, could be expected to contain two types of small subunits, one derived from N. sylvestris and the other from a paternal progenitor. N. sylvestris lacks two of the 25 chymotryptic peptides of the small subunit of N. tabacum. Among 3 putative paternal progenitors, these two peaks appeared only in N. tomentosiformis, but not in Nicotiana otophora or K-12. Thus, N. tomentosiformis was concluded to be a paternal progenitor of N. tabacum. The conclusion was verified by comparing chymotryptic peptides of small subunits from three amphidiploids of N. sylvestris crossed with N. tomentosiformis, N. sylvestris crossed with N. otophora snd N. sylvestris crossed with K-12. The analytical results showed that only the progeny of N. sylvestris crossed with N. tomentosiformis contained the same small subunits as N. tabacium.", "contents": "Origin of Nicotiana tabacum detected by primary structure of fraction I protein. Nicotiana tabacum is believed to have arisen after hybridization of Nicotiana sylvestris with a species in the Tomentosae section of the genus Nicotiana. Recent biochemical experiments have confirmed the conclusions from previous cytogenetic studies that N. sylvestris was the maternal parent and have indicated that Nicotiana tomentosiformis was the paternal parent. However, these studies did not take into account the possibility that a new species of Nicotiana, called K-12, discovered in South America in 1968, could also have been one of the parents. Fraction I proteins were purified from N. tabacum and its putative progenitors, and separated into large and small subunits. Chymotryptic peptides of each subunit were analyzed by ion exchange column chromatography with a gradient elution system. Among 38 resolved peaks of the large subunits, 2 peaks were found to be different among the putative species. Since only N. sylvestris showed an identical chromatogram with N. tabacum, N. sylvestris was concluded to be the maternal progenitor, as the genetic information for the large subunit of Fraction I protein was known to be inherited by the cytoplasmic mode. On the other hand, the small subunit of Fraction I protein is inherited by the Mendelian mode and therefore N. tabacum, an allopolyploid, could be expected to contain two types of small subunits, one derived from N. sylvestris and the other from a paternal progenitor. N. sylvestris lacks two of the 25 chymotryptic peptides of the small subunit of N. tabacum. Among 3 putative paternal progenitors, these two peaks appeared only in N. tomentosiformis, but not in Nicotiana otophora or K-12. Thus, N. tomentosiformis was concluded to be a paternal progenitor of N. tabacum. The conclusion was verified by comparing chymotryptic peptides of small subunits from three amphidiploids of N. sylvestris crossed with N. tomentosiformis, N. sylvestris crossed with N. otophora snd N. sylvestris crossed with K-12. The analytical results showed that only the progeny of N. sylvestris crossed with N. tomentosiformis contained the same small subunits as N. tabacium."} {"id": "PMID:1260010", "title": "Subunit structure of bovine milk xanthine oxidase. Effect of limited cleavage by proteolytic enzymes on activity and structure.", "content": "Bovine milk xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) has been purified by a modified method without the use of proteases, and its structure has been analyzed by polyacrylamide gel electrophoresis. Native xanthine oxidase is found to consist of only two polypeptide chains A with molecular weights of 150 000 each. These chains have NH2-terminal methionine. Limited proteolysis with trypsin, chymotrypsin, or subtilisin at pH 8 did not affect molecular weight and activities of the enzyme while each of the A chains was cleaved under these conditions to three fragments C, E, and F with molecular weights of 92 00, 42 000 and 20 000, respectively. These fragments remained bound to each other and were relatively resistant to subsequent proteolysis. The isolation of xanthine oxidase in the presence of pancreatin as described by Hart et al. (1970, Biochem. J. 116, 851) gives partially digested enzyme composed mainly of chains C, E (Mr 35 000) and a small component (Mr approx. 15 0-0). The action of subtilisin on xanthine oxidase at pH 11 resulted in complete digestion of E chains, FAD separation, and total loss of xanthine:oxygen oxidoreductase activity while xanthine:indophenol oxidoreductase activity was relatively little affected. The residual enzyme has a molecular weight of about 200 000, is composed mainly of two C chains (and may probably contain F and/or proteolytic fragments of low molecular weight), contains molybdenum, and does not contain FAD.", "contents": "Subunit structure of bovine milk xanthine oxidase. Effect of limited cleavage by proteolytic enzymes on activity and structure. Bovine milk xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.2.3.2) has been purified by a modified method without the use of proteases, and its structure has been analyzed by polyacrylamide gel electrophoresis. Native xanthine oxidase is found to consist of only two polypeptide chains A with molecular weights of 150 000 each. These chains have NH2-terminal methionine. Limited proteolysis with trypsin, chymotrypsin, or subtilisin at pH 8 did not affect molecular weight and activities of the enzyme while each of the A chains was cleaved under these conditions to three fragments C, E, and F with molecular weights of 92 00, 42 000 and 20 000, respectively. These fragments remained bound to each other and were relatively resistant to subsequent proteolysis. The isolation of xanthine oxidase in the presence of pancreatin as described by Hart et al. (1970, Biochem. J. 116, 851) gives partially digested enzyme composed mainly of chains C, E (Mr 35 000) and a small component (Mr approx. 15 0-0). The action of subtilisin on xanthine oxidase at pH 11 resulted in complete digestion of E chains, FAD separation, and total loss of xanthine:oxygen oxidoreductase activity while xanthine:indophenol oxidoreductase activity was relatively little affected. The residual enzyme has a molecular weight of about 200 000, is composed mainly of two C chains (and may probably contain F and/or proteolytic fragments of low molecular weight), contains molybdenum, and does not contain FAD."} {"id": "PMID:1260011", "title": "Structural studies on a glycoprotein isolated from alveoli of patients with alveolar proteinosis.", "content": "A major glycoprotein 36 000 molecular weight) has been isolated from lung lavage of patients with alveolar proteinosis and found to contain five residues of hydroxyproline, fifty residues of glycine, three residues of methionine, 3 mol of sialic acid, 4.4 mol of mannose, 4.0 mol of galactose, 6.0 mol of glucosamine, and 1 mol of fucose. Cyanogen bromide (CNBr) treatment of the glycoprotein resulted, as expected, in four peptides of apparent molecular weights of 18 000, 12 000, 5000 and 1000, respectively. The chemical compositions of the CNBr peptides indicate the presence of hydroxyproline and high amounts of glycine in all but one of the peptides; two of the four CNBr peptides contain carbohydrate. Gel filtration, acrylamide gel electrophoresis and end-group analyses of the native glycoprotein and its CNBr peptides indicate that the peptides are homogeneous. End-group analyses of the CNBr cleavage products assign the 18 000 molecular weight peptide to the NH2-terminal portion and the 1000 molecular weight peptide to the COOH-terminal portion of the native glycoprotein molecule. Pronase digestion of the 36 000 molecular weight glycoprotein, followed by gel filtration and cation exchange chromatography, resulted in two fractions. One fraction was acidic and contained all the carbohydrate, a high content of aspartic acid and no hydroxyproline. The other fraction was basic and contained 8.4% hydroxyproline, 14% proline, 28% glycine and no carbohydrate, suggesting the presence of collagen-like sequence in the peptide chain. Paper electrophoresis of the basic fraction demonstrated two components, the amino acid compositions of which are identical to those of collagen. Partial amino-terminal sequence analysis of one of the CNBr peptides (18 000 molecular weight) indicated the presence of -Fly-Pro-HyP-Gly-sequence in the peptide chain, which confirms our suggestion that collagen-like regions are present in the native glycoprotein molecule. Limited acid hydrolysis of the acidic fraction and subsequent fractionation of the acid hydrolysate using Dowex column yielded a fraction which produced brown colour with ninhydrin reagent. Paper chromatography of this fraction demonstrated a large component which also stained brown with ninhydrin reagent. After acid hydrolysis, this component was found to consist of equal amounts of asparitic acid and glucosamine, indicating that the N-acetylglucosamine of the oligosaccharides is linked to the asparagine residue of the peptide. No serine or threonine linkages are present.", "contents": "Structural studies on a glycoprotein isolated from alveoli of patients with alveolar proteinosis. A major glycoprotein 36 000 molecular weight) has been isolated from lung lavage of patients with alveolar proteinosis and found to contain five residues of hydroxyproline, fifty residues of glycine, three residues of methionine, 3 mol of sialic acid, 4.4 mol of mannose, 4.0 mol of galactose, 6.0 mol of glucosamine, and 1 mol of fucose. Cyanogen bromide (CNBr) treatment of the glycoprotein resulted, as expected, in four peptides of apparent molecular weights of 18 000, 12 000, 5000 and 1000, respectively. The chemical compositions of the CNBr peptides indicate the presence of hydroxyproline and high amounts of glycine in all but one of the peptides; two of the four CNBr peptides contain carbohydrate. Gel filtration, acrylamide gel electrophoresis and end-group analyses of the native glycoprotein and its CNBr peptides indicate that the peptides are homogeneous. End-group analyses of the CNBr cleavage products assign the 18 000 molecular weight peptide to the NH2-terminal portion and the 1000 molecular weight peptide to the COOH-terminal portion of the native glycoprotein molecule. Pronase digestion of the 36 000 molecular weight glycoprotein, followed by gel filtration and cation exchange chromatography, resulted in two fractions. One fraction was acidic and contained all the carbohydrate, a high content of aspartic acid and no hydroxyproline. The other fraction was basic and contained 8.4% hydroxyproline, 14% proline, 28% glycine and no carbohydrate, suggesting the presence of collagen-like sequence in the peptide chain. Paper electrophoresis of the basic fraction demonstrated two components, the amino acid compositions of which are identical to those of collagen. Partial amino-terminal sequence analysis of one of the CNBr peptides (18 000 molecular weight) indicated the presence of -Fly-Pro-HyP-Gly-sequence in the peptide chain, which confirms our suggestion that collagen-like regions are present in the native glycoprotein molecule. Limited acid hydrolysis of the acidic fraction and subsequent fractionation of the acid hydrolysate using Dowex column yielded a fraction which produced brown colour with ninhydrin reagent. Paper chromatography of this fraction demonstrated a large component which also stained brown with ninhydrin reagent. After acid hydrolysis, this component was found to consist of equal amounts of asparitic acid and glucosamine, indicating that the N-acetylglucosamine of the oligosaccharides is linked to the asparagine residue of the peptide. No serine or threonine linkages are present."} {"id": "PMID:1260012", "title": "Prolactin binding in rat mammary gland during pregnancy and lactation.", "content": "Lactogenic hormones from the placenta and pituitary are primarily responsible for the growth and function of the mammary gland during pregnancy and lactation. In the present study we described the optimal conditions for the measurement of 125I-labeled ovine prolactin binding to mammary gland slices of pregnant and lactating rats. Prolactin binding is saturable (Kd approx. 2.36 - 10(-9) M), hormone specific and destroyed by proteases. The hormonal environments of pregnancy and lactation dramatically influence the availability and measurement of prolactin binding sites. Whereas binding consistently appears to be low in mammary glands removed from rats during pregnancy, binding levels rise 7--8-fold shortly after birth and remain high during the 22 days of lactation. However, the removal of the ovaries and gravid uteri at specific times during pregnancy results in a prompt 3--6-fold increase in prolactin binding. Elevated levels in potential prolactin binding capacity appear in mammary tissue coincident with the reported rise in serum rat placental lactogen between the eighth and eleventh days. We suggest that high levels of this lactogenic hormone promote the appearance of prolactin binding sites during pregnancy and mask the sites such that they are not available for measurement in vitro.", "contents": "Prolactin binding in rat mammary gland during pregnancy and lactation. Lactogenic hormones from the placenta and pituitary are primarily responsible for the growth and function of the mammary gland during pregnancy and lactation. In the present study we described the optimal conditions for the measurement of 125I-labeled ovine prolactin binding to mammary gland slices of pregnant and lactating rats. Prolactin binding is saturable (Kd approx. 2.36 - 10(-9) M), hormone specific and destroyed by proteases. The hormonal environments of pregnancy and lactation dramatically influence the availability and measurement of prolactin binding sites. Whereas binding consistently appears to be low in mammary glands removed from rats during pregnancy, binding levels rise 7--8-fold shortly after birth and remain high during the 22 days of lactation. However, the removal of the ovaries and gravid uteri at specific times during pregnancy results in a prompt 3--6-fold increase in prolactin binding. Elevated levels in potential prolactin binding capacity appear in mammary tissue coincident with the reported rise in serum rat placental lactogen between the eighth and eleventh days. We suggest that high levels of this lactogenic hormone promote the appearance of prolactin binding sites during pregnancy and mask the sites such that they are not available for measurement in vitro."} {"id": "PMID:1260013", "title": "Interactions of cadmium and selenium in rat plasma in vivo and in vitro.", "content": "75Se and 109Cd tracers were used to study the binding of Se and Cd to plasma proteins at various SeO32- doses and times upt to 24 h after the simultaneous subcutaneous administration of SeO32- markedly increased both Se and Cd plasma levels over that in control animals. Gel permeation chromatography of plasma indicated that at all times up to 24 h Cd and Se were bound in an atomic ratio of approx. 1 : 1 in 330 000 and 130 000 dalton fractions. From 4 to 24 h, Cd and Se appeared in the 420 000 dalton fraction, also with an atomic ratio of approx. 1 : 1. The 330 000 dalton molecules appeared to have a maximal binding capacity for the Cd-Se complex at a concentration of approx. 30 mumol/ml of plasma, while the 130 000 and 420 000 dalton molecules show a higher binding capacity. Studies in vitro revealed that SeO32- does not interact directly with Cd and plasma proteins. It is metabolized by erythrocytes to a form that interacts in an atomic ratio of 1 : 1 with Cd to form a protein-bound complex of 130 000 daltons.", "contents": "Interactions of cadmium and selenium in rat plasma in vivo and in vitro. 75Se and 109Cd tracers were used to study the binding of Se and Cd to plasma proteins at various SeO32- doses and times upt to 24 h after the simultaneous subcutaneous administration of SeO32- markedly increased both Se and Cd plasma levels over that in control animals. Gel permeation chromatography of plasma indicated that at all times up to 24 h Cd and Se were bound in an atomic ratio of approx. 1 : 1 in 330 000 and 130 000 dalton fractions. From 4 to 24 h, Cd and Se appeared in the 420 000 dalton fraction, also with an atomic ratio of approx. 1 : 1. The 330 000 dalton molecules appeared to have a maximal binding capacity for the Cd-Se complex at a concentration of approx. 30 mumol/ml of plasma, while the 130 000 and 420 000 dalton molecules show a higher binding capacity. Studies in vitro revealed that SeO32- does not interact directly with Cd and plasma proteins. It is metabolized by erythrocytes to a form that interacts in an atomic ratio of 1 : 1 with Cd to form a protein-bound complex of 130 000 daltons."} {"id": "PMID:1260014", "title": "Ethanol metabolism and lipid synthesis by isolated liver cells from fed rats.", "content": "1. The fatty acid synthesis in isolated liver cells from fed rats was studied with tritiated water as the radioactive precursor. The cells incorporated 3H20 at a rate of 1.26 mumol per min per g packed cells. 2. Addition of ethanol caused a 20% decrease in the incorporation of tritium into fatty acids. The decrease was correlated to the increase in the NAD-redox level. Probably, the decreased tritium incorporation into fatty acids during ethanol metabolism is due to a decrease in the specific activity of the NADPH used for the synthesis of fatty acids, rather than to a real inhibition of the fatty acid synthesis. 3. Ethanol oxidation via NADPH-consuming pathways and ethanol per se at a concentration of 80 mM had no effect upon the incorporation of tritium into fatty acids. 4. Fructose in a concentration of 15 mM inhibited the fatty acid synthesis by 75%, and this inhibition was further augmented by ethanol. 5. The ioslated rat liver cells oxidized ethanol at a rate of 2.72, 2.93 and 3.48 mumol per min per g packed cells at 5, 20 and 80 mM ethanol, respectively. Fructose had no effect upon ethanol oxidation neither at low nor at high concentrations of ethanol. 6. Ethanol oxidation via the non alcohol dehydrogenase pathway(s) may involve a transfer of reducing equivalents from mitochondrial NADH to cyctosolic NADP+ as judged from measurements of metabolite levels. This conclusion is supported by determinations of 14C yield in glucose from [1-14C] ethanol, and the results are taken as evidence for the presence of hydrogen shuttle activity during metabolism of ethanol, catalyzed by the NAD-dependent alcohol dehydrogenase. A metabolic scheme is proposed to account for the observed changes at low and high concentrations of ethanol.", "contents": "Ethanol metabolism and lipid synthesis by isolated liver cells from fed rats. 1. The fatty acid synthesis in isolated liver cells from fed rats was studied with tritiated water as the radioactive precursor. The cells incorporated 3H20 at a rate of 1.26 mumol per min per g packed cells. 2. Addition of ethanol caused a 20% decrease in the incorporation of tritium into fatty acids. The decrease was correlated to the increase in the NAD-redox level. Probably, the decreased tritium incorporation into fatty acids during ethanol metabolism is due to a decrease in the specific activity of the NADPH used for the synthesis of fatty acids, rather than to a real inhibition of the fatty acid synthesis. 3. Ethanol oxidation via NADPH-consuming pathways and ethanol per se at a concentration of 80 mM had no effect upon the incorporation of tritium into fatty acids. 4. Fructose in a concentration of 15 mM inhibited the fatty acid synthesis by 75%, and this inhibition was further augmented by ethanol. 5. The ioslated rat liver cells oxidized ethanol at a rate of 2.72, 2.93 and 3.48 mumol per min per g packed cells at 5, 20 and 80 mM ethanol, respectively. Fructose had no effect upon ethanol oxidation neither at low nor at high concentrations of ethanol. 6. Ethanol oxidation via the non alcohol dehydrogenase pathway(s) may involve a transfer of reducing equivalents from mitochondrial NADH to cyctosolic NADP+ as judged from measurements of metabolite levels. This conclusion is supported by determinations of 14C yield in glucose from [1-14C] ethanol, and the results are taken as evidence for the presence of hydrogen shuttle activity during metabolism of ethanol, catalyzed by the NAD-dependent alcohol dehydrogenase. A metabolic scheme is proposed to account for the observed changes at low and high concentrations of ethanol."} {"id": "PMID:1260015", "title": "Evidence for multiple enzymes in the dolichol utilizing pathway of glycoprotein biosynthesis.", "content": "A comparison has been made of the enzymes catalyzing the transfer of mannose, glucose and N-acetylglucosamine from, respectively, GDPmannose, UDP-glucose and UDP-N-acetylglucosamine to endogenous dolichol phosphate (Dol-P) in liver Golgi membranes. Evidence is presented with suggests that all three reactions utilize the same pool of Dol-P. The transfer of mannose from GDP-Man to Dol-P is not inhibited by 0.1 mM UDP or UMP; 0.1 mM GDP did block the accumulation of mannose in Dol-P-Man. The net transfer of glucose and N-acetylglucosamine to Dol-P is prevented by 0.1 mM UDP but not 0.1 mM GDP. UDPglucose inhibits the reverse of the glucose transfer reaction but not the reverse of the N-acetylglucosamine or mannose trasfer reaction. On the basis of this, and other data, it is concluded that the three sugar transfer reactions utilize separate enzymes.", "contents": "Evidence for multiple enzymes in the dolichol utilizing pathway of glycoprotein biosynthesis. A comparison has been made of the enzymes catalyzing the transfer of mannose, glucose and N-acetylglucosamine from, respectively, GDPmannose, UDP-glucose and UDP-N-acetylglucosamine to endogenous dolichol phosphate (Dol-P) in liver Golgi membranes. Evidence is presented with suggests that all three reactions utilize the same pool of Dol-P. The transfer of mannose from GDP-Man to Dol-P is not inhibited by 0.1 mM UDP or UMP; 0.1 mM GDP did block the accumulation of mannose in Dol-P-Man. The net transfer of glucose and N-acetylglucosamine to Dol-P is prevented by 0.1 mM UDP but not 0.1 mM GDP. UDPglucose inhibits the reverse of the glucose transfer reaction but not the reverse of the N-acetylglucosamine or mannose trasfer reaction. On the basis of this, and other data, it is concluded that the three sugar transfer reactions utilize separate enzymes."} {"id": "PMID:1260016", "title": "The derivatization of oxidized polysaccharides for protein immobilization and affinity chromatography.", "content": "The present report describes the preparation of modified polysaccharides matrices useful for the synthesis of affinity adsorbents and immobilized proteins. Hydrazido-matrices were synthesized by condensing an excess of the bifunctional reagent, adipic acid dihydrazide, with periodate oxidized cellulose paper, Sephadex, or Sepharose matrices. Ribonucleotide dialdehyde cofactors, glyceraldehyde 3-phosphate, pyridoxal 5'-phosphate and oxidized DNAase B were separately bound to the hydrazido-polymers. Azido-matrices obtained by modification of the hydrazido-derivatives were coupled to specific amino ligands such as amino acids and proteins. Several adsorbents were prepared and used as models for affinity chromatography.", "contents": "The derivatization of oxidized polysaccharides for protein immobilization and affinity chromatography. The present report describes the preparation of modified polysaccharides matrices useful for the synthesis of affinity adsorbents and immobilized proteins. Hydrazido-matrices were synthesized by condensing an excess of the bifunctional reagent, adipic acid dihydrazide, with periodate oxidized cellulose paper, Sephadex, or Sepharose matrices. Ribonucleotide dialdehyde cofactors, glyceraldehyde 3-phosphate, pyridoxal 5'-phosphate and oxidized DNAase B were separately bound to the hydrazido-polymers. Azido-matrices obtained by modification of the hydrazido-derivatives were coupled to specific amino ligands such as amino acids and proteins. Several adsorbents were prepared and used as models for affinity chromatography."} {"id": "PMID:1260017", "title": "The distribution of chondroitin sulfates in articular and growth cartilages of human bones.", "content": "The relative contents of chondroitin 4- and 6-sulfates in cartilages of different human bones are reported. Articular and vertebral body cartilages contain almost exclusively chondroitin 6-sulfate, whereas growth and subarticular cartilages contain nearly equal amounts of chondroitin 4-sulfate and chondroitin 6-sulfate. Adult cartilages, where the calcification process is complete, contain only chondroitin 6-sulfate. These results that chondroitin 4-sulfate may be an important component for the calcification process, whereas chondroitin 6-sulfate seems to be related to the integrity of the articular surfaces. A chemical defect of chondroitin 6-sulfate in a new mucopolysaccharidosis, characterized by platyspondyly and irregularities of articular surfaces, is in agreement with these results.", "contents": "The distribution of chondroitin sulfates in articular and growth cartilages of human bones. The relative contents of chondroitin 4- and 6-sulfates in cartilages of different human bones are reported. Articular and vertebral body cartilages contain almost exclusively chondroitin 6-sulfate, whereas growth and subarticular cartilages contain nearly equal amounts of chondroitin 4-sulfate and chondroitin 6-sulfate. Adult cartilages, where the calcification process is complete, contain only chondroitin 6-sulfate. These results that chondroitin 4-sulfate may be an important component for the calcification process, whereas chondroitin 6-sulfate seems to be related to the integrity of the articular surfaces. A chemical defect of chondroitin 6-sulfate in a new mucopolysaccharidosis, characterized by platyspondyly and irregularities of articular surfaces, is in agreement with these results."} {"id": "PMID:1260018", "title": "The content of water and potassium in fat cells.", "content": "The distribution spaces at equilibrium for 3H2O, [14C]urea and s-O-[14C]-methylglucose were measured in white fat cells using centrifugation through silicone oil at 2500 X g; no significant differences were observed. L-[14C]Glucose added immediately before the centrifugation was used as a marker for the extracellular water space. The calculated intracellular water content of the cells after the centrifugation through oil (e.g. 3H2O space minus L-[14C]glucose space) is an unbiased measure of the water content of the fat cells in suspension as judged by the following criteria: (1) The intracellular distribution space for 3-O-[14C]'methylglucose at equilibrium (methylglucose space minus L-glucose space) was not different from that calculated from a methylglucose wash-out curve. (2) The intracellular content of L-[14C]glucose (half time of efflux about 60 min) in cells preloaded during incubation of the tissue with collagenase was not different in cells recovered by (a) centrifugation through oil at 2500 X g, (b) centrifugation through oil at 600 X g, (c) centrifugation at 600 X g in the absence of oil and (d) filtration on Millipore filters. The intracellular content of water determined on cells from single rats weighing 120-150 g was 2.75 +/- 0.55 mul/100 mul fat cells (+/- S.D., n = 30). The intracellular content of potassium, determined on cells from the same rats, was 252 +/- 62 nmols/100 mul fat cells (+/- S.D., n = 30). The concentration of potassium in the intracellular water was calculated as 104 +/- 15 mM (+/- S.D., n = 30).", "contents": "The content of water and potassium in fat cells. The distribution spaces at equilibrium for 3H2O, [14C]urea and s-O-[14C]-methylglucose were measured in white fat cells using centrifugation through silicone oil at 2500 X g; no significant differences were observed. L-[14C]Glucose added immediately before the centrifugation was used as a marker for the extracellular water space. The calculated intracellular water content of the cells after the centrifugation through oil (e.g. 3H2O space minus L-[14C]glucose space) is an unbiased measure of the water content of the fat cells in suspension as judged by the following criteria: (1) The intracellular distribution space for 3-O-[14C]'methylglucose at equilibrium (methylglucose space minus L-glucose space) was not different from that calculated from a methylglucose wash-out curve. (2) The intracellular content of L-[14C]glucose (half time of efflux about 60 min) in cells preloaded during incubation of the tissue with collagenase was not different in cells recovered by (a) centrifugation through oil at 2500 X g, (b) centrifugation through oil at 600 X g, (c) centrifugation at 600 X g in the absence of oil and (d) filtration on Millipore filters. The intracellular content of water determined on cells from single rats weighing 120-150 g was 2.75 +/- 0.55 mul/100 mul fat cells (+/- S.D., n = 30). The intracellular content of potassium, determined on cells from the same rats, was 252 +/- 62 nmols/100 mul fat cells (+/- S.D., n = 30). The concentration of potassium in the intracellular water was calculated as 104 +/- 15 mM (+/- S.D., n = 30)."} {"id": "PMID:1260019", "title": "The interaction of adeninylalkylcobalamins with ribonucleotide reductase.", "content": "Several structural analogs of adenosylcobalamin, containing 2, 3, 4, 5 and 6 methylene carbons instead of the ribofuranose moiety, have been synthesized and their interaction with ribonucleotide reductase from Lactobacillus leichmannii has been investigated. Kinetic studies of the inhibition of the reductase by these analogs showed that the adeninylalkylcobalamins with 4, 5 and 6 carbons interposed between the adenine moiety and the cobalt atom are potent inhibitors of ribonucleotide reduction. The stronger interaction between adeninylpentylcobalamin and the enzyme than that between adenosylcobalamin and the enzyme suggests that the more flexible acyclic analog of adenosine requires fewer adjustments of the protein upon binding.", "contents": "The interaction of adeninylalkylcobalamins with ribonucleotide reductase. Several structural analogs of adenosylcobalamin, containing 2, 3, 4, 5 and 6 methylene carbons instead of the ribofuranose moiety, have been synthesized and their interaction with ribonucleotide reductase from Lactobacillus leichmannii has been investigated. Kinetic studies of the inhibition of the reductase by these analogs showed that the adeninylalkylcobalamins with 4, 5 and 6 carbons interposed between the adenine moiety and the cobalt atom are potent inhibitors of ribonucleotide reduction. The stronger interaction between adeninylpentylcobalamin and the enzyme than that between adenosylcobalamin and the enzyme suggests that the more flexible acyclic analog of adenosine requires fewer adjustments of the protein upon binding."} {"id": "PMID:1260020", "title": "Cellulose synthesis by extracts of Acanthamoeba castellanii during encystment. Stimulation of the incorporation of radioactivity from UDP-(14C)glucose into alkali-soluble and insoluble beta-glucans by glucose 6-phosphate and related compounds.", "content": "1. The activity of a particulate enzyme prepared from encysting cells of Acanthamoeba castellanii (Neff), previously shown to catalyze the incorporation of glucose from UDP-[14C]glucose into both alkali-soluble and alkali-insoluble beta-(1 leads to 4) glucans, was stimulated several fold by glucose-6-phosphate and several related compounds. 2. Incorporation was observed when [14C]glucose-6-P was incubated with the particles in the presence of UDP-glucose. The results of product analysis by partial acid hydrolysis indicated that glucose-6-P stimulates the formation of both alkali-soluble and alkali-insoluble beta-(1 leads to 4) glucans from UDP-[14C]glucose and was itself incorporated into an alkali-insoluble beta-(1 leads to 4)glucan. 3. When particles incubated with UDP-[14C]glucose and glucose-6-P were reisolated and then reincubated with unlabeled UDP-glucose and glucose-6-P, a loss of counts from the alkali-soluble fraction was detected along with a corresponding rise in the radioactivity of the alkali-insoluble fraction. This suggests that the alkali-soluble beta-glucan was converted to an alkali-insoluble product and possibly may be an intermediate stage in cellulose synthesis.", "contents": "Cellulose synthesis by extracts of Acanthamoeba castellanii during encystment. Stimulation of the incorporation of radioactivity from UDP-(14C)glucose into alkali-soluble and insoluble beta-glucans by glucose 6-phosphate and related compounds. 1. The activity of a particulate enzyme prepared from encysting cells of Acanthamoeba castellanii (Neff), previously shown to catalyze the incorporation of glucose from UDP-[14C]glucose into both alkali-soluble and alkali-insoluble beta-(1 leads to 4) glucans, was stimulated several fold by glucose-6-phosphate and several related compounds. 2. Incorporation was observed when [14C]glucose-6-P was incubated with the particles in the presence of UDP-glucose. The results of product analysis by partial acid hydrolysis indicated that glucose-6-P stimulates the formation of both alkali-soluble and alkali-insoluble beta-(1 leads to 4) glucans from UDP-[14C]glucose and was itself incorporated into an alkali-insoluble beta-(1 leads to 4)glucan. 3. When particles incubated with UDP-[14C]glucose and glucose-6-P were reisolated and then reincubated with unlabeled UDP-glucose and glucose-6-P, a loss of counts from the alkali-soluble fraction was detected along with a corresponding rise in the radioactivity of the alkali-insoluble fraction. This suggests that the alkali-soluble beta-glucan was converted to an alkali-insoluble product and possibly may be an intermediate stage in cellulose synthesis."} {"id": "PMID:1260021", "title": "Thrombin-induced oxygen consumption, malonyldialdehyde formation and serotonin secretion in human platelets.", "content": "The relationship of a thrombin-induced burst in O2 consumption to lipid peroxidation in washed human platelets was investigated by measuring malonyldialdehyde, a by-product of endoperoxide degradation in platelets. The ratio of O2 consumed by malonyldialdehyde produced was approximately 7:1. Acetylsalicylate blocked the formation of malonyldialdehyde completely and partially inhibited the O2 burst induced by thrombin. 5,8,11,14-Eicosatetraynoic acid inhibited the O2 burst as well as the malonyldialdehyde formation completely. The release of [14C]serotonin was not affected by either inhibitor.", "contents": "Thrombin-induced oxygen consumption, malonyldialdehyde formation and serotonin secretion in human platelets. The relationship of a thrombin-induced burst in O2 consumption to lipid peroxidation in washed human platelets was investigated by measuring malonyldialdehyde, a by-product of endoperoxide degradation in platelets. The ratio of O2 consumed by malonyldialdehyde produced was approximately 7:1. Acetylsalicylate blocked the formation of malonyldialdehyde completely and partially inhibited the O2 burst induced by thrombin. 5,8,11,14-Eicosatetraynoic acid inhibited the O2 burst as well as the malonyldialdehyde formation completely. The release of [14C]serotonin was not affected by either inhibitor."} {"id": "PMID:1260022", "title": "Decreased riboflavin formation in mutants of Aerobacter (Enterobacter) aerogenes deficient in the butanediol pathway.", "content": "Riboflavin concentration increased linearly for more than 60 h in wild type cultures, whereas in three mutants deficient in the formation of acetoin and 2,3-butanediol the production ceased at the end of exponential growth.", "contents": "Decreased riboflavin formation in mutants of Aerobacter (Enterobacter) aerogenes deficient in the butanediol pathway. Riboflavin concentration increased linearly for more than 60 h in wild type cultures, whereas in three mutants deficient in the formation of acetoin and 2,3-butanediol the production ceased at the end of exponential growth."} {"id": "PMID:1260023", "title": "Binding of bovine brain tissue factor to concanavalin A-Sepharose. Partial purification of coagulant, arylamidase, and alkaline phosphatase activities.", "content": "Tissue factor coagulant activity is adsorbed onto concanavalin A-Sepharose from sodium deoxycholate extracts of delipidated bovine brain powders. Coagulant activity is eluted with alpha-methyl-D-glucoside in sodium deoxycholate with 2--25-fold purification. This material has the same coagulant specific activity as that previously prepared in this laboratory. Alkaline phosphatase and alanyl-beta-naphthylamidase activities in the detergent extract also bind to concanavalin A-Sepharose and elute under the same conditions with 4- and 7-fold purification. In addition to these biological activities, the eluate was composed of protein (67.7%), neutral and amino sugars and sialic acid (22.3%), phospholipid (4.5%), uronic acid (3.8%) and nucleic acid (1.7%). This preparation is slightly enriched in carbohydrates compared to previous preparations. Concanavalian A-Sepharose therefore appears to be useful material for partial purification of several mammalian plasma membrane components with retention of biological function.", "contents": "Binding of bovine brain tissue factor to concanavalin A-Sepharose. Partial purification of coagulant, arylamidase, and alkaline phosphatase activities. Tissue factor coagulant activity is adsorbed onto concanavalin A-Sepharose from sodium deoxycholate extracts of delipidated bovine brain powders. Coagulant activity is eluted with alpha-methyl-D-glucoside in sodium deoxycholate with 2--25-fold purification. This material has the same coagulant specific activity as that previously prepared in this laboratory. Alkaline phosphatase and alanyl-beta-naphthylamidase activities in the detergent extract also bind to concanavalin A-Sepharose and elute under the same conditions with 4- and 7-fold purification. In addition to these biological activities, the eluate was composed of protein (67.7%), neutral and amino sugars and sialic acid (22.3%), phospholipid (4.5%), uronic acid (3.8%) and nucleic acid (1.7%). This preparation is slightly enriched in carbohydrates compared to previous preparations. Concanavalian A-Sepharose therefore appears to be useful material for partial purification of several mammalian plasma membrane components with retention of biological function."} {"id": "PMID:1260024", "title": "Inhibition of platelet aggregation by acyl-CoA thioesters.", "content": "The aggregation of platelets induced by ADP, collagen, or epinephrine in human platelet-rich plasma is inhibited by long chain acyl-CoA thioesters. Palmityl-CoA exerts a concentration dependent inhibition of collagen-induced aggregation and of the primary and secondary waves of ADP-induced aggregation. Palmityl-CoA also inhibits the secondary wave of epinephrine-induced aggregation but has no effect on the primary wave. This inhibitory effect of palmityl-CoA can be reversed by addition of excess ADP and cannot be attributed to a detergent action.", "contents": "Inhibition of platelet aggregation by acyl-CoA thioesters. The aggregation of platelets induced by ADP, collagen, or epinephrine in human platelet-rich plasma is inhibited by long chain acyl-CoA thioesters. Palmityl-CoA exerts a concentration dependent inhibition of collagen-induced aggregation and of the primary and secondary waves of ADP-induced aggregation. Palmityl-CoA also inhibits the secondary wave of epinephrine-induced aggregation but has no effect on the primary wave. This inhibitory effect of palmityl-CoA can be reversed by addition of excess ADP and cannot be attributed to a detergent action."} {"id": "PMID:1260025", "title": "Subcellular distribution of S-adenosylmethionine decarboxylase in rat liver. Evidence of decarboxylation of S-adenosylmethionine separate from synthesis of spermidine.", "content": "The activity of S-adenosylmethionine decarboxylase in rat liver homogenates is localized chiefly in the crude nuclear fraction, probably associated with membrane fragments, with the remainder in the supernatant fraction. This distribution is not paralleled by the activity of the cytoplasmic enzyme, lactate dehydrogenase. The spermidine-synthesizing activity of whole homogenate is recovered entirely in the supermidine-synthesizing activity of whole homogenate is recovered entirely in the supernatant fraction. Measurement of various kinetic parameters in crude fractions provided not positive evidence for isozymes of S-adenosylmethionine decarboxylase. Some species do not possess a sedimentable fraction of S-adenosylmethionine decarboxylase activity in liver. In those species all activity present in the whole homogenate of liver is released into the supernatant fraction.", "contents": "Subcellular distribution of S-adenosylmethionine decarboxylase in rat liver. Evidence of decarboxylation of S-adenosylmethionine separate from synthesis of spermidine. The activity of S-adenosylmethionine decarboxylase in rat liver homogenates is localized chiefly in the crude nuclear fraction, probably associated with membrane fragments, with the remainder in the supernatant fraction. This distribution is not paralleled by the activity of the cytoplasmic enzyme, lactate dehydrogenase. The spermidine-synthesizing activity of whole homogenate is recovered entirely in the supermidine-synthesizing activity of whole homogenate is recovered entirely in the supernatant fraction. Measurement of various kinetic parameters in crude fractions provided not positive evidence for isozymes of S-adenosylmethionine decarboxylase. Some species do not possess a sedimentable fraction of S-adenosylmethionine decarboxylase activity in liver. In those species all activity present in the whole homogenate of liver is released into the supernatant fraction."} {"id": "PMID:1260026", "title": "Changes in subcellular distribution of S-adenosylmethionine decarboxylase in regenerating and in developing rat liver.", "content": "Distribution of the activity of S-adenosylmethionine decarboxylase in homogenates of rat liver regenerating after partial hepatectomy and during development are reported. In the stages of rapid growth of liver remaining after partial hepatectomy, an increased activity of S-adenosylmethionine decarboxylase in the supernatant fractions is accompanied by a decreased activity in the crude nuclear fractions. Prior to birth, in the liver of the developing rat, all activity of S-adenosylmethionine decarboxylase is in the supernatant fraction. After birth, activity in the crude nuclear fraction increases rapidly, reaching adult values by the end of weaning.", "contents": "Changes in subcellular distribution of S-adenosylmethionine decarboxylase in regenerating and in developing rat liver. Distribution of the activity of S-adenosylmethionine decarboxylase in homogenates of rat liver regenerating after partial hepatectomy and during development are reported. In the stages of rapid growth of liver remaining after partial hepatectomy, an increased activity of S-adenosylmethionine decarboxylase in the supernatant fractions is accompanied by a decreased activity in the crude nuclear fractions. Prior to birth, in the liver of the developing rat, all activity of S-adenosylmethionine decarboxylase is in the supernatant fraction. After birth, activity in the crude nuclear fraction increases rapidly, reaching adult values by the end of weaning."} {"id": "PMID:1260027", "title": "Proton NMR study of coordinated imidazoles in low-spin ferric heme complexes. Assignment of single proton histidine resonance in hemoproteins.", "content": "The proton signals for the coordinated axial imidazoles in a series of low-spin ferric bis-imidazole complexes with natural porphyrin derivatives have been located and assigned. The methyl signals of several methyl-substituted imidazoles have also been resolved for the mixed ligand complexes of imidazole and cyanide ion. The imidazole spectra for the bis complexes are essentially the same as those reported earlier for synthetic porphyrins, with the hyperfine shifts exhibiting comparable contributions from the dipolar and contact interactions. The contact contribution reflects spin transfer into a vacant imidazole pi orbital. The spectra of both the mono- and bis-imidazole complex concur in predicting that only the 2-H and 5-CH2 signals of an axial histidine are likely to resonate clearly outside the diamagnetic 0 to --10 ppm from TMS region in hemoproteins. However, both the 2-H and 4-H imidazole peaks are found to be too broad to detect in a hemoprotein. Hence, it is suggested that the pair of non-heme, single-proton resonances in low-spin met-myoglobin cyanides arise from the non-equivalent methylene protons at the 5-position of the histidyl imidazole. Both the resonance positions and relative linewidths in the model compounds are consistent with the data for this pair of protons in myoglobins. The possible interpretations of the average downfield bias of these signals as well as the magnitude of their spacing, are discussed in terms of the conformation of the proximal histidine relative to the heme group.", "contents": "Proton NMR study of coordinated imidazoles in low-spin ferric heme complexes. Assignment of single proton histidine resonance in hemoproteins. The proton signals for the coordinated axial imidazoles in a series of low-spin ferric bis-imidazole complexes with natural porphyrin derivatives have been located and assigned. The methyl signals of several methyl-substituted imidazoles have also been resolved for the mixed ligand complexes of imidazole and cyanide ion. The imidazole spectra for the bis complexes are essentially the same as those reported earlier for synthetic porphyrins, with the hyperfine shifts exhibiting comparable contributions from the dipolar and contact interactions. The contact contribution reflects spin transfer into a vacant imidazole pi orbital. The spectra of both the mono- and bis-imidazole complex concur in predicting that only the 2-H and 5-CH2 signals of an axial histidine are likely to resonate clearly outside the diamagnetic 0 to --10 ppm from TMS region in hemoproteins. However, both the 2-H and 4-H imidazole peaks are found to be too broad to detect in a hemoprotein. Hence, it is suggested that the pair of non-heme, single-proton resonances in low-spin met-myoglobin cyanides arise from the non-equivalent methylene protons at the 5-position of the histidyl imidazole. Both the resonance positions and relative linewidths in the model compounds are consistent with the data for this pair of protons in myoglobins. The possible interpretations of the average downfield bias of these signals as well as the magnitude of their spacing, are discussed in terms of the conformation of the proximal histidine relative to the heme group."} {"id": "PMID:1260029", "title": "Purification of rat adipose tissue lipoprotein lipase by affinity chromatography.", "content": "Lipoprotein lipase (EC 3.1.1.3) from rat adipose tissue was purified by affinity chromatography with heparin-Sepharose. Elution was carried out with buffered solutions of increasing NaCl molarity. Proteins without affinity for heparin were eluted with 0.5 M NaCl, while lipoprotein lipase activity was eluted as two peaks with 1.16 M NaCl (In earlier work on human adipose tissue (Etienne et al. (1974) C.R. Acad. Sc. Paris 279, 1487-1490) two fractions with lipoprotein lipase activity were also obtained). Phospholipase activity was detected in the fraction eluted with buffered 0.5 M NaCl and containing proteins without affinity for heparin. On feeding the fasting rats with fresh cream or glucose two peaks were also obtained, but the first peak had clearly increased while the second one had remained virtually unchanged.", "contents": "Purification of rat adipose tissue lipoprotein lipase by affinity chromatography. Lipoprotein lipase (EC 3.1.1.3) from rat adipose tissue was purified by affinity chromatography with heparin-Sepharose. Elution was carried out with buffered solutions of increasing NaCl molarity. Proteins without affinity for heparin were eluted with 0.5 M NaCl, while lipoprotein lipase activity was eluted as two peaks with 1.16 M NaCl (In earlier work on human adipose tissue (Etienne et al. (1974) C.R. Acad. Sc. Paris 279, 1487-1490) two fractions with lipoprotein lipase activity were also obtained). Phospholipase activity was detected in the fraction eluted with buffered 0.5 M NaCl and containing proteins without affinity for heparin. On feeding the fasting rats with fresh cream or glucose two peaks were also obtained, but the first peak had clearly increased while the second one had remained virtually unchanged."} {"id": "PMID:1260030", "title": "Specificity and distribution of mammalian carnosinase.", "content": "Hog kidney carnosinase (EC 3.4.13.3) was found to have a narrow specificity; it hydrolyzed carnosine, anserine and glycyl-L-histidine, but did not split L-alanyl-L-histidine or homocarnosine. The isoelectric point of this enzyme was 5.8 and its molecular weight was about 84 000. Carnosinase was found to be widely distributed in various tissues of the rat. Uterus, kidney, liver and lung contained high levels of carnosinase, whereas moderate concentrations were found in spleen, heart and brain, with low levels in small intestine, skeletal muscle and stomach, and none in blood.", "contents": "Specificity and distribution of mammalian carnosinase. Hog kidney carnosinase (EC 3.4.13.3) was found to have a narrow specificity; it hydrolyzed carnosine, anserine and glycyl-L-histidine, but did not split L-alanyl-L-histidine or homocarnosine. The isoelectric point of this enzyme was 5.8 and its molecular weight was about 84 000. Carnosinase was found to be widely distributed in various tissues of the rat. Uterus, kidney, liver and lung contained high levels of carnosinase, whereas moderate concentrations were found in spleen, heart and brain, with low levels in small intestine, skeletal muscle and stomach, and none in blood."} {"id": "PMID:1260031", "title": "Identification of an active site histidine in urokinase.", "content": "Two forms of urokinase (EC 3.4.99.26) with apparent molecular weights of 33 400 and 47 000 purified by affinity chromatography have been modified specifically with newly synthesized peptide chloroketones by affinity labeline. Rapid inactivation of the enzyme preparations was observed with Ac-Gly-Lys-CH2 Cl and Nle-Gly-Lys-CH2 Cl which might be associated with a change in which a histidine residue is lost. After performic acid oxidation, an equivalent amount of 3-carboxymethyl histidine could be recovered, indicating alkylation at the N-3 of a histidine residue. In the case of the norleucine derivative, norleucine was concomitantly incorporated into the protein. It is thus likely that urokinase belongs in the class of enzymes utilizing the Asp..His..Ser triad for their catalytic action. The two active site residues so far identified, serine and histidine, were located in the heavy chain (33 100 mol. wt) of the 47 000 molecular weight form and in the 33 400 molecular weight form, the molecular weight of which remained constant.", "contents": "Identification of an active site histidine in urokinase. Two forms of urokinase (EC 3.4.99.26) with apparent molecular weights of 33 400 and 47 000 purified by affinity chromatography have been modified specifically with newly synthesized peptide chloroketones by affinity labeline. Rapid inactivation of the enzyme preparations was observed with Ac-Gly-Lys-CH2 Cl and Nle-Gly-Lys-CH2 Cl which might be associated with a change in which a histidine residue is lost. After performic acid oxidation, an equivalent amount of 3-carboxymethyl histidine could be recovered, indicating alkylation at the N-3 of a histidine residue. In the case of the norleucine derivative, norleucine was concomitantly incorporated into the protein. It is thus likely that urokinase belongs in the class of enzymes utilizing the Asp..His..Ser triad for their catalytic action. The two active site residues so far identified, serine and histidine, were located in the heavy chain (33 100 mol. wt) of the 47 000 molecular weight form and in the 33 400 molecular weight form, the molecular weight of which remained constant."} {"id": "PMID:1260032", "title": "Microcalorimetric methods for substrate determination in flow systems with immobilized enzymes.", "content": "The enthalpy of processes catalyzed by immobilized enzymes in the reaction cell of a LKB-flow calorimeter is used for determination of urea (0.5-5 mumol) and glucose (0.03-0.5 mumol). Accuracy is 2-5% and the time needed for one analysis is 20 min. A sensitive \"enzyme thermistor\" consisting of a flow through cell with an immobilized enzyme and two thermistors is described, which permits glucose determinations (0.05-1 mumol +/- 0.03 mumol) by means of temperature difference caused by reaction heat. Coupling of enzyme reactions for increasing reaction heat and consequently sensitivity in calorimetric determinations is demonstrated.", "contents": "Microcalorimetric methods for substrate determination in flow systems with immobilized enzymes. The enthalpy of processes catalyzed by immobilized enzymes in the reaction cell of a LKB-flow calorimeter is used for determination of urea (0.5-5 mumol) and glucose (0.03-0.5 mumol). Accuracy is 2-5% and the time needed for one analysis is 20 min. A sensitive \"enzyme thermistor\" consisting of a flow through cell with an immobilized enzyme and two thermistors is described, which permits glucose determinations (0.05-1 mumol +/- 0.03 mumol) by means of temperature difference caused by reaction heat. Coupling of enzyme reactions for increasing reaction heat and consequently sensitivity in calorimetric determinations is demonstrated."} {"id": "PMID:1260033", "title": "Mechanism of action of putrescine oxidase. Binding characteristics of the active site of putrescine oxidase from Micrococcus rubens.", "content": "Putrescine oxidase (EC 1.4.3.4), putrescine: oxygen oxidoreductase (deaminating) (flavin containing), has been found to form complexes with a variety of amines. With few exceptions these compounds competitively inhibit putrescine oxidation and also perturb the visible absorption spectrum of the enzyme (i.e., the spectrum due to FAD). Inhibition constants are reported for a number of amines; the presence of a cationic amino group in the inhibitors appears to be the structural feature essential for competitive inhibition. Inhibition constants for amino acids are larger than those for the analogous simple amines and the inhibition constants for alkyl mono- and diamines in a homologous series are inversely related to the length of the hydrocarbon chain. Amines containing unsaturated and aromatic substituents yield relatively low inhibition constants. The spectral changes observed upon complex formation are interpreted as indicating a less polar environment for FAD in the enzyme-inhibitor complex than in the uncomplexed enzyme. On the basis of the enzyme's substrate specificity and comparisons among inhibitor structures and the corresponding inhibition constants, a schematic model of the enzyme's active site is proposed.", "contents": "Mechanism of action of putrescine oxidase. Binding characteristics of the active site of putrescine oxidase from Micrococcus rubens. Putrescine oxidase (EC 1.4.3.4), putrescine: oxygen oxidoreductase (deaminating) (flavin containing), has been found to form complexes with a variety of amines. With few exceptions these compounds competitively inhibit putrescine oxidation and also perturb the visible absorption spectrum of the enzyme (i.e., the spectrum due to FAD). Inhibition constants are reported for a number of amines; the presence of a cationic amino group in the inhibitors appears to be the structural feature essential for competitive inhibition. Inhibition constants for amino acids are larger than those for the analogous simple amines and the inhibition constants for alkyl mono- and diamines in a homologous series are inversely related to the length of the hydrocarbon chain. Amines containing unsaturated and aromatic substituents yield relatively low inhibition constants. The spectral changes observed upon complex formation are interpreted as indicating a less polar environment for FAD in the enzyme-inhibitor complex than in the uncomplexed enzyme. On the basis of the enzyme's substrate specificity and comparisons among inhibitor structures and the corresponding inhibition constants, a schematic model of the enzyme's active site is proposed."} {"id": "PMID:1260034", "title": "Brain UDPgalactose: ceramide galactosyltransferase Purification of a catalytically active protein obtained after proteolytic digestion.", "content": "A procedure for the purification of UDPgalactose--2-hydroxyacylsphingosine galactosyltransferase (EC 2.4.1.45) including detergent extraction, ion-excharge chromatography and proteolytic digestion was developed. The active fraction obtained by this procedure had about 100 times higher specific activity than microsomes. Enzymic activity resisted destruction by pronase treatment at 4 degrees C. Agarose gel chromatography indicated the presence of an enzyme-phospholipid-detergent complex with a molecular weight between 400 000 and 500 000. Intact phospholipids seemed to be required for full enzymic activity as evidenced by the drastic loss of activity upon treatment with phospholipase A or C.", "contents": "Brain UDPgalactose: ceramide galactosyltransferase Purification of a catalytically active protein obtained after proteolytic digestion. A procedure for the purification of UDPgalactose--2-hydroxyacylsphingosine galactosyltransferase (EC 2.4.1.45) including detergent extraction, ion-excharge chromatography and proteolytic digestion was developed. The active fraction obtained by this procedure had about 100 times higher specific activity than microsomes. Enzymic activity resisted destruction by pronase treatment at 4 degrees C. Agarose gel chromatography indicated the presence of an enzyme-phospholipid-detergent complex with a molecular weight between 400 000 and 500 000. Intact phospholipids seemed to be required for full enzymic activity as evidenced by the drastic loss of activity upon treatment with phospholipase A or C."} {"id": "PMID:1260035", "title": "Alkaline phosphatase in HeLa cells. Stimulation by phospholipase A2 and lysophosphatidylcholine.", "content": "Treatment of homogenates and plasma membrane preparations from HeLa cells with phospholipase A2 (EC 3.1.1.4) caused a 50% increase in activity of membrane-associated alkaline phosphatase. Lysophosphatidylcholine, dispersed in 0.15 M KCl, affected alkaline phosphatase in a similar fashion by releasing the enzyme from particulate fractions into the incubation medium and by elevating its specific activity. Higher concentrations of lysophosphatidylcholine solubilized additional protein from particulate fractions but did not further increase the specific activity of the released alkaline phosphatase. Particulate fractions from HeLa cells were exposed to the effects of liposomes prepared from lysophosphatidylcholine and cholesterol. The ratio of particulate protein/lysophosphatidylcholine (by weight) required for optimal activation of alkaline phosphatase was one. Kinetic studies indicated that phospholipase A2 and lysophosphatidylcholine enhanced the apparent V of the enzyme but did not significantly alter its apparent Km. The increased release of alkaline phosphatase from the particulate matrix by lysophosphatidylcholine was confirmed by disc electrophoresis. The release of the enzyme by either phospholipase A2 or by lysophosphatidylcholine appeared to be followed by the formation of micelles that contained lysophosphatidylcholine. The new complexes had relatively less cholesterol and more lysophosphatidylcholine than the native membranes. The possibility that lysophosphatidylcholine formed a lipoprotein complex with the solubilized alkaline phosphatase was indicated by a break point in the Arrhenius plot which was evident only in the lysophosphatidylcholine-solubilized enzyme but could not be demonstrated in alkaline phosphatase that had been released with 0.15 M KCl alone.", "contents": "Alkaline phosphatase in HeLa cells. Stimulation by phospholipase A2 and lysophosphatidylcholine. Treatment of homogenates and plasma membrane preparations from HeLa cells with phospholipase A2 (EC 3.1.1.4) caused a 50% increase in activity of membrane-associated alkaline phosphatase. Lysophosphatidylcholine, dispersed in 0.15 M KCl, affected alkaline phosphatase in a similar fashion by releasing the enzyme from particulate fractions into the incubation medium and by elevating its specific activity. Higher concentrations of lysophosphatidylcholine solubilized additional protein from particulate fractions but did not further increase the specific activity of the released alkaline phosphatase. Particulate fractions from HeLa cells were exposed to the effects of liposomes prepared from lysophosphatidylcholine and cholesterol. The ratio of particulate protein/lysophosphatidylcholine (by weight) required for optimal activation of alkaline phosphatase was one. Kinetic studies indicated that phospholipase A2 and lysophosphatidylcholine enhanced the apparent V of the enzyme but did not significantly alter its apparent Km. The increased release of alkaline phosphatase from the particulate matrix by lysophosphatidylcholine was confirmed by disc electrophoresis. The release of the enzyme by either phospholipase A2 or by lysophosphatidylcholine appeared to be followed by the formation of micelles that contained lysophosphatidylcholine. The new complexes had relatively less cholesterol and more lysophosphatidylcholine than the native membranes. The possibility that lysophosphatidylcholine formed a lipoprotein complex with the solubilized alkaline phosphatase was indicated by a break point in the Arrhenius plot which was evident only in the lysophosphatidylcholine-solubilized enzyme but could not be demonstrated in alkaline phosphatase that had been released with 0.15 M KCl alone."} {"id": "PMID:1260036", "title": "The common identity of five glycosidases in human liver.", "content": "An enzyme has been isolated from human liver by DEAE-cellulose chromatography and has been shown by competitive substrate inhibition to be capable of hydrolysing synthetic beta-D-galactosides, beta-D-glucosides, beta-D-fucosides, beta-D-xylosides, and alpha-L-arabinosides. Another form of alpha-L-arabinosidase activity elutes with the major beta-D-galactosidase component on DEAE-chromatography, but has a different identity on the basis of its stability at 4 degrees C. Liver samples from patients with Gaucher's disease are deficient in beta-D-fucosidase as well as beta-D-glucosidase activity.", "contents": "The common identity of five glycosidases in human liver. An enzyme has been isolated from human liver by DEAE-cellulose chromatography and has been shown by competitive substrate inhibition to be capable of hydrolysing synthetic beta-D-galactosides, beta-D-glucosides, beta-D-fucosides, beta-D-xylosides, and alpha-L-arabinosides. Another form of alpha-L-arabinosidase activity elutes with the major beta-D-galactosidase component on DEAE-chromatography, but has a different identity on the basis of its stability at 4 degrees C. Liver samples from patients with Gaucher's disease are deficient in beta-D-fucosidase as well as beta-D-glucosidase activity."} {"id": "PMID:1260037", "title": "Human alpha-fucosidase. Purification and properties.", "content": "Human placental alpha-fucosidase (EC 3.2.1.51) has been extensively purified and partially characterized with respect to kinetic and structured properties. Although the enzyme seems to be separated by DEAE-cellulose chromatography in two forms which differ in their molecular weight and thermostability, an interconversion between the two forms takes place during storage and/or electrofocusing so that the same peaks of activity, revealed by the latter technique, are found before and after DEAE-cellulose chrome. The heterogeneous peaks of activity revealed by isoelectrofocusing show a reproducible pattern in the different tissues examined, except in serum where their pI values are consistently more acidic.", "contents": "Human alpha-fucosidase. Purification and properties. Human placental alpha-fucosidase (EC 3.2.1.51) has been extensively purified and partially characterized with respect to kinetic and structured properties. Although the enzyme seems to be separated by DEAE-cellulose chromatography in two forms which differ in their molecular weight and thermostability, an interconversion between the two forms takes place during storage and/or electrofocusing so that the same peaks of activity, revealed by the latter technique, are found before and after DEAE-cellulose chrome. The heterogeneous peaks of activity revealed by isoelectrofocusing show a reproducible pattern in the different tissues examined, except in serum where their pI values are consistently more acidic."} {"id": "PMID:1260038", "title": "On the subunit structure of particulate aminopeptidase from pig kidney.", "content": "Solubilization of particulate aminopeptidase (EC 3.4.11.2) from pig kidney with Triton X-100 yields an aggregate (mol. wt. approx. 10(6)) that decomposes into \"free\" aminopeptidase (mol. wt. 280 000) either upon autolysis at pH 5 or after exposure to trypsin. Both procedures yield free enzymes that are identical with respect to electrophoretic mobility, enzymatic activity and zinc content. After dissociation, the enzyme resulting from autolysis yields a single subunit of 140 000 molecular weight while the trypsin-treated enzyme produces three fragments (140 000, 95 000 and 48 000 mol. wt.). As the aggregate is formed by subunits 10 000 daltons heavier than those of the free enzyme, the existence of a hydrophobic portion anchoring the enzyme to the membrane might be postulated. Reactivation experiments carried out on the three purified fragments of urea-denatured aminopeptidase show that the 140 000 molecular weight subunit is the only one able to yield an active enzyme (after spontaneous dimerization). It can be concluded that the smaller fragments are artefacts resulting from trypsin degradation during purification.", "contents": "On the subunit structure of particulate aminopeptidase from pig kidney. Solubilization of particulate aminopeptidase (EC 3.4.11.2) from pig kidney with Triton X-100 yields an aggregate (mol. wt. approx. 10(6)) that decomposes into \"free\" aminopeptidase (mol. wt. 280 000) either upon autolysis at pH 5 or after exposure to trypsin. Both procedures yield free enzymes that are identical with respect to electrophoretic mobility, enzymatic activity and zinc content. After dissociation, the enzyme resulting from autolysis yields a single subunit of 140 000 molecular weight while the trypsin-treated enzyme produces three fragments (140 000, 95 000 and 48 000 mol. wt.). As the aggregate is formed by subunits 10 000 daltons heavier than those of the free enzyme, the existence of a hydrophobic portion anchoring the enzyme to the membrane might be postulated. Reactivation experiments carried out on the three purified fragments of urea-denatured aminopeptidase show that the 140 000 molecular weight subunit is the only one able to yield an active enzyme (after spontaneous dimerization). It can be concluded that the smaller fragments are artefacts resulting from trypsin degradation during purification."} {"id": "PMID:1260039", "title": "The identity of the elastase-associated acidic endopeptidase and chymotrypsin C from porcine pancreas.", "content": "The preparations of chymotrypsin C (EC 3.4.21.2) and an acidic endopeptidase from porcine pancreas have been repeated using published procedures. The acidic endopeptidase showed lower activity than chymotrypsin C in all comparative experiments, but it was possible to precipitate a fraction from the acidic endopeptidase preparation which contained all the protein and was identical with chymotrypsin C. It is concluded that the acidic endopeptidase is identical with chymotrypsin C but it is contaminated by an inert non-protein material to which it is firmly bound. The formation of a precipitate, at low ionic strength, from mixtures of chymotrypsin C and elastase (EC 3.4.21.11) is independent of the availability of the active site of either enzyme.", "contents": "The identity of the elastase-associated acidic endopeptidase and chymotrypsin C from porcine pancreas. The preparations of chymotrypsin C (EC 3.4.21.2) and an acidic endopeptidase from porcine pancreas have been repeated using published procedures. The acidic endopeptidase showed lower activity than chymotrypsin C in all comparative experiments, but it was possible to precipitate a fraction from the acidic endopeptidase preparation which contained all the protein and was identical with chymotrypsin C. It is concluded that the acidic endopeptidase is identical with chymotrypsin C but it is contaminated by an inert non-protein material to which it is firmly bound. The formation of a precipitate, at low ionic strength, from mixtures of chymotrypsin C and elastase (EC 3.4.21.11) is independent of the availability of the active site of either enzyme."} {"id": "PMID:1260040", "title": "Substrate specificity of the L-serine O-sulphate degrading activities of Pseudomonas FR.", "content": "1. Two enzyme systems obtained from Pseudomonas FR capable of catalysing the alphabeta-elimination of L-serine O-sulphate exhibit a wide range of substrate specificity. Greatest activity was exhibited towards beta-substituted serine and cysteine derivatives. Enzyme A shows a marked preference for the L-isomeric form and enzyme B shows a preference for D-isomers. 2. The alternative activities were shown to be properties of the same enzyme by inhibition properties and heat denaturation experiments. 3. The assay of enzyme A by a number of alternative substrates at various stages during its purification confirmed the multi-substrate specificity of the system. 4. Growth of Pseudomonas FR on S-methyl-L-cysteine as the sole carbon source also resulted in the induction of enzyme B. Growth patterns and levels of induced enzyme were similar to those obtained when L-serine O-sulphate was employed in comparable circumstances.", "contents": "Substrate specificity of the L-serine O-sulphate degrading activities of Pseudomonas FR. 1. Two enzyme systems obtained from Pseudomonas FR capable of catalysing the alphabeta-elimination of L-serine O-sulphate exhibit a wide range of substrate specificity. Greatest activity was exhibited towards beta-substituted serine and cysteine derivatives. Enzyme A shows a marked preference for the L-isomeric form and enzyme B shows a preference for D-isomers. 2. The alternative activities were shown to be properties of the same enzyme by inhibition properties and heat denaturation experiments. 3. The assay of enzyme A by a number of alternative substrates at various stages during its purification confirmed the multi-substrate specificity of the system. 4. Growth of Pseudomonas FR on S-methyl-L-cysteine as the sole carbon source also resulted in the induction of enzyme B. Growth patterns and levels of induced enzyme were similar to those obtained when L-serine O-sulphate was employed in comparable circumstances."} {"id": "PMID:1260041", "title": "Isolation of rabbit muscle glucosephosphate isomerase by a single-step substrate elution.", "content": "A simple method has been developed for the rapid isolation of crystalline glucosephosphate isomerase (EC 5.3.1.9) from rabbit muscle. The enzyme is first bound to cellulose phosphate by adding the ion exchanger to a solution of the crude tissue extract. After filtering and washing the cellulose with buffer, the isomerase is specifically eluted in a batch process by its substrate, glucose 6-phosphate. The entire procedure is very rapid and results in a good recovery (at least 50%) of the enzyme with specific activity of approximately 900 units per mg. The enzyme is homogeneous by polyacrylamide gel electrophoresis in the presence of absence of sodium dodecyl sulfate and by analytical ultracentrifugation.", "contents": "Isolation of rabbit muscle glucosephosphate isomerase by a single-step substrate elution. A simple method has been developed for the rapid isolation of crystalline glucosephosphate isomerase (EC 5.3.1.9) from rabbit muscle. The enzyme is first bound to cellulose phosphate by adding the ion exchanger to a solution of the crude tissue extract. After filtering and washing the cellulose with buffer, the isomerase is specifically eluted in a batch process by its substrate, glucose 6-phosphate. The entire procedure is very rapid and results in a good recovery (at least 50%) of the enzyme with specific activity of approximately 900 units per mg. The enzyme is homogeneous by polyacrylamide gel electrophoresis in the presence of absence of sodium dodecyl sulfate and by analytical ultracentrifugation."} {"id": "PMID:1260042", "title": "Light-dependent development of photosynthetic competence in Scenedesmus mutant No. 8.", "content": "The heterotrophically grown, P-700-free mutant No. 8 of Scenedesmus obliquus is unable to carry out photosynthesis. Yet, chloroplast particles isolated from the alga reduced ferricyanide. They also reduced methyl viologen in the presence of the artificial donor reduced 2,6-dichlorophenol indophenol with a low yield but an appreciable saturation rate. NADP reduction or P-700 turn-over could not be detected. When grown mixotrophically, the mutant showed increasing P-700 activity with a concomitant increase in the rate of photosynthesis. Both activities were lost again when the algae were returned to darkness. Isolated chloroplast particles showed a good P-700 turn-over and reasonable rates of NADP reduction. The data suggest that the mutation occurred at a site preceding the formation of the pigment. The results on the photochemical activities are discussed in the light of reports concerning the involvement of P-700 in linear electron transport.", "contents": "Light-dependent development of photosynthetic competence in Scenedesmus mutant No. 8. The heterotrophically grown, P-700-free mutant No. 8 of Scenedesmus obliquus is unable to carry out photosynthesis. Yet, chloroplast particles isolated from the alga reduced ferricyanide. They also reduced methyl viologen in the presence of the artificial donor reduced 2,6-dichlorophenol indophenol with a low yield but an appreciable saturation rate. NADP reduction or P-700 turn-over could not be detected. When grown mixotrophically, the mutant showed increasing P-700 activity with a concomitant increase in the rate of photosynthesis. Both activities were lost again when the algae were returned to darkness. Isolated chloroplast particles showed a good P-700 turn-over and reasonable rates of NADP reduction. The data suggest that the mutation occurred at a site preceding the formation of the pigment. The results on the photochemical activities are discussed in the light of reports concerning the involvement of P-700 in linear electron transport."} {"id": "PMID:1260043", "title": "The study of the primary photoprocesses in photosystem I of chloroplasts. Recombination luminescence, chlorophyll triplet state and triplet-triplet annihilation.", "content": "The dependence of the delayed luminescence of Photosystem I on the state of the reaction centers has been studied. Light flash induces a charge separation in the centers: P-700-P-430 hv in equilibrium P-700+-P-430-. Dark recombination of charges is accompanied by the recombination luminescence with tau1/2 congruent to 20ms. If the centers are in the P-700-P-430- state or if P-430 is inactivated by heat, then flashing of Photosystem I generates the triplet state chlorophyll with tau1/2 congruent to 0.5 ms. The triplet state has been measured by the delayed fluorescence of chlorophyll at 20 degrees C and 77 degrees K and by the chlorophyll phosphorescence at 77 degrees K. The delayed fluorescence at 20 degrees C arises from the thermal activation of the triplet state up to the excited singlet level of chlorophyll and at 77 degrees K it is due to triplet-triplet annihilation. The quantum yield of the triplet formation, estimated by a comparison of the light saturation curves of delayed fluorescence at 20 degrees C and of P-700 photooxidation under the same experimental (optical) conditions, is approximately 0.9 of the P-700+ yield. Only one triplet of chlorophyll can be generated per P-700. Under heat inactivation of P-430 the triplet formation is not observed when P-700 is oxidized. It is assumed that the triplet-triplet annihilation at 77 degrees K is related with the strong interaction between the chlorophyll molecules in the pigment complex of Photosystem I. The possibility of a triplet participation in the primary processes of photosynthesis is discussed.", "contents": "The study of the primary photoprocesses in photosystem I of chloroplasts. Recombination luminescence, chlorophyll triplet state and triplet-triplet annihilation. The dependence of the delayed luminescence of Photosystem I on the state of the reaction centers has been studied. Light flash induces a charge separation in the centers: P-700-P-430 hv in equilibrium P-700+-P-430-. Dark recombination of charges is accompanied by the recombination luminescence with tau1/2 congruent to 20ms. If the centers are in the P-700-P-430- state or if P-430 is inactivated by heat, then flashing of Photosystem I generates the triplet state chlorophyll with tau1/2 congruent to 0.5 ms. The triplet state has been measured by the delayed fluorescence of chlorophyll at 20 degrees C and 77 degrees K and by the chlorophyll phosphorescence at 77 degrees K. The delayed fluorescence at 20 degrees C arises from the thermal activation of the triplet state up to the excited singlet level of chlorophyll and at 77 degrees K it is due to triplet-triplet annihilation. The quantum yield of the triplet formation, estimated by a comparison of the light saturation curves of delayed fluorescence at 20 degrees C and of P-700 photooxidation under the same experimental (optical) conditions, is approximately 0.9 of the P-700+ yield. Only one triplet of chlorophyll can be generated per P-700. Under heat inactivation of P-430 the triplet formation is not observed when P-700 is oxidized. It is assumed that the triplet-triplet annihilation at 77 degrees K is related with the strong interaction between the chlorophyll molecules in the pigment complex of Photosystem I. The possibility of a triplet participation in the primary processes of photosynthesis is discussed."} {"id": "PMID:1260044", "title": "Transient inhibition by ribose 5-phosphate of photosynthetic O2 evolution in a reconstituted chloroplast system.", "content": "Photosynthetic oxygen evolution by a reconstituted chloroplast system utilising sn-phospho-3-glycerol (3-phosphoglycerate) ceases upon the addition of ribose 5-phosphate even though the presence of this metabolite permits a rapid and immediate CO2 fixation. The period of cessation is appreciable at 0.1 mM ribose 5-phosphate. It is lengthened as the amount of added ribose 5-phosphate is increased and by the addition of dithiothreitol, a known activator of ribulose-5-phosphate kinase. Ribulose 1,5-bisphosphate is without effect. A similar interruption of O2 evolution may also be brought about by the addition of ADP or by ADP-generating systems such as glucose plus hexokinase. Spectrophotometric experiments indicate that the reoxidation of NADPH in the presence of sn-phospho-3-glycerol is similarly affected. The transient inhibition by ribose 5-phosphate is not observed in the presence of an active ATP-generating system or in the presence of sufficient DL-glyceraldehyde to inhibit ribulose-5-phosphate kinase activity. It is concluded that ribose 5-phosphate inhibits photosynthetic O2 evolution by adversely affecting the steady-state ATP/ADP ratio and consequently the reduction of sn-phospho-3-glycerol to glyceraldehyde 3-phosphate. The results are discussed in their relation to ADP regulation of photosynthetic carbon assimilation and metabolite transport.", "contents": "Transient inhibition by ribose 5-phosphate of photosynthetic O2 evolution in a reconstituted chloroplast system. Photosynthetic oxygen evolution by a reconstituted chloroplast system utilising sn-phospho-3-glycerol (3-phosphoglycerate) ceases upon the addition of ribose 5-phosphate even though the presence of this metabolite permits a rapid and immediate CO2 fixation. The period of cessation is appreciable at 0.1 mM ribose 5-phosphate. It is lengthened as the amount of added ribose 5-phosphate is increased and by the addition of dithiothreitol, a known activator of ribulose-5-phosphate kinase. Ribulose 1,5-bisphosphate is without effect. A similar interruption of O2 evolution may also be brought about by the addition of ADP or by ADP-generating systems such as glucose plus hexokinase. Spectrophotometric experiments indicate that the reoxidation of NADPH in the presence of sn-phospho-3-glycerol is similarly affected. The transient inhibition by ribose 5-phosphate is not observed in the presence of an active ATP-generating system or in the presence of sufficient DL-glyceraldehyde to inhibit ribulose-5-phosphate kinase activity. It is concluded that ribose 5-phosphate inhibits photosynthetic O2 evolution by adversely affecting the steady-state ATP/ADP ratio and consequently the reduction of sn-phospho-3-glycerol to glyceraldehyde 3-phosphate. The results are discussed in their relation to ADP regulation of photosynthetic carbon assimilation and metabolite transport."} {"id": "PMID:1260045", "title": "Site specific inhibition by alpha-benzyl-alpha-bromomalodinitrile (BBMD) of electron transport in spinach chloroplasts.", "content": "The addition of alpha-benzyl-alpha-bromomalodinitrile to different controlled states (non-phosphorylating [2]. phosphorylating [3], ATP-inhibited [4] and uncoupled) of photosynthetic electron transport to ferricyanide or benzoquinone demonstrate a significant inhibition in isolated spinach chloroplasts. alpha-Benzyl-alpha-bromomalodinitrile pretreatement of isolated chloroplasts or addition of alpha-benzyl-alpha-bromomalodinitrile at the onset of illumination completely abolished the O2 evolving reaction. The level of the steady state fluorescence in intact chloroplasts showed a alpha-benzyl-alpha-bromomalodinitrile concentration-dependent increase. The gradual decrease in the reoxidation capacity of the reduced quencher, Q with increasing alpha-benzyl-alpha-bromomalodinitrile concentrations provides evidence for an additional inhibitory site for alpha-benzyl-alpha-bromomalodinitrile between the two photosystems.", "contents": "Site specific inhibition by alpha-benzyl-alpha-bromomalodinitrile (BBMD) of electron transport in spinach chloroplasts. The addition of alpha-benzyl-alpha-bromomalodinitrile to different controlled states (non-phosphorylating [2]. phosphorylating [3], ATP-inhibited [4] and uncoupled) of photosynthetic electron transport to ferricyanide or benzoquinone demonstrate a significant inhibition in isolated spinach chloroplasts. alpha-Benzyl-alpha-bromomalodinitrile pretreatement of isolated chloroplasts or addition of alpha-benzyl-alpha-bromomalodinitrile at the onset of illumination completely abolished the O2 evolving reaction. The level of the steady state fluorescence in intact chloroplasts showed a alpha-benzyl-alpha-bromomalodinitrile concentration-dependent increase. The gradual decrease in the reoxidation capacity of the reduced quencher, Q with increasing alpha-benzyl-alpha-bromomalodinitrile concentrations provides evidence for an additional inhibitory site for alpha-benzyl-alpha-bromomalodinitrile between the two photosystems."} {"id": "PMID:1260046", "title": "Phthalonic acid, an inhibitor of alpha-oxoglutarate transport in mitochondria.", "content": "Phthalonic acid is a powerful inhibitor of alpha-oxoglutarate transport in mitochondria. This conclusion is based on the following observations: 1. Phthalonic acid inhibits the oxidation of alpha-oxoglutarate but has no effect on the oxidation of glutamate or cis-aconitate. 2. With arsenite present, phthalonic acid inhibits the oxidation of glutamate plus malate and of cis-aconitate plus malate. Under these conditions alpha-oxoglutarate accumulates inside the mitochondria. With glutamate plus malate as substrates the inhibition is competitive with malate with a Ki value of 20 muM. 3. Phthalonic acid inhibits the oxidation of intramitochondrial NAD(P)H by alpha-oxoglutarate plus ammonia. The inhibition is competitive with respect to alpha-oxoglutarate with a Ki of 30 muM. 4. Phthalonic acid inhibits the exchange between extramitochondrial alpha-oxoglutarate and intramitochondrial malate.", "contents": "Phthalonic acid, an inhibitor of alpha-oxoglutarate transport in mitochondria. Phthalonic acid is a powerful inhibitor of alpha-oxoglutarate transport in mitochondria. This conclusion is based on the following observations: 1. Phthalonic acid inhibits the oxidation of alpha-oxoglutarate but has no effect on the oxidation of glutamate or cis-aconitate. 2. With arsenite present, phthalonic acid inhibits the oxidation of glutamate plus malate and of cis-aconitate plus malate. Under these conditions alpha-oxoglutarate accumulates inside the mitochondria. With glutamate plus malate as substrates the inhibition is competitive with malate with a Ki value of 20 muM. 3. Phthalonic acid inhibits the oxidation of intramitochondrial NAD(P)H by alpha-oxoglutarate plus ammonia. The inhibition is competitive with respect to alpha-oxoglutarate with a Ki of 30 muM. 4. Phthalonic acid inhibits the exchange between extramitochondrial alpha-oxoglutarate and intramitochondrial malate."} {"id": "PMID:1260047", "title": "The effect of ribose 5-phosphate and 5-phosphoribosyl-1-pyrophosphate availability on de novo synthesis of purine nucleotides in rat liver slices.", "content": "The effect of increasing cellular ribose 5-phosphate (ribose-5-P) availability by methylene blue-induced acceleration of the oxidative pentose phosphate pathway on the rate of 5-phosphoribosyl-1-pyrophosphate (P-ribose-PP) generation, was studied in slices of rat liver at varying Pi concentration. It was found that at Pi concentration prevailing in the tissue of extracellular physiological Pi concentration, ribose-5-P availability is saturating for P-ribose-PP generation, as gauged by the rate of adenine incorporation into tissue nucleotides. The effect of altering P-ribose-PP availability on the rate of de novo purine production gauged by the rate of formate incorporation into purines, was also studied. It was found that the physiological P-ribose-PP concentration in rat liver tissue is limiting for purine synthesis de novo. Depletion of cellular P-ribose-PP, achieved by increase of P-ribose-PP consumption, decelerated purine synthesis, while increase of P-ribose-PP availability, achieved by activation of P-ribose-PP synthetase occurring at elevated Pi concentration, resulted in acceleration of purine synthesis.", "contents": "The effect of ribose 5-phosphate and 5-phosphoribosyl-1-pyrophosphate availability on de novo synthesis of purine nucleotides in rat liver slices. The effect of increasing cellular ribose 5-phosphate (ribose-5-P) availability by methylene blue-induced acceleration of the oxidative pentose phosphate pathway on the rate of 5-phosphoribosyl-1-pyrophosphate (P-ribose-PP) generation, was studied in slices of rat liver at varying Pi concentration. It was found that at Pi concentration prevailing in the tissue of extracellular physiological Pi concentration, ribose-5-P availability is saturating for P-ribose-PP generation, as gauged by the rate of adenine incorporation into tissue nucleotides. The effect of altering P-ribose-PP availability on the rate of de novo purine production gauged by the rate of formate incorporation into purines, was also studied. It was found that the physiological P-ribose-PP concentration in rat liver tissue is limiting for purine synthesis de novo. Depletion of cellular P-ribose-PP, achieved by increase of P-ribose-PP consumption, decelerated purine synthesis, while increase of P-ribose-PP availability, achieved by activation of P-ribose-PP synthetase occurring at elevated Pi concentration, resulted in acceleration of purine synthesis."} {"id": "PMID:1260048", "title": "In vivo isotope incorporation patterns into HeLa ribosomal proteins.", "content": "When cells were incubated with L-[35S] methionine plus L-[Me-3H] methionine, it was found that at least four ribosomal proteins had 3H/35S ratios higher than the rest of the ribosomal proteins, suggesting that they were methylated. The rate of apparent methylation paralleled the rate of amino acid incorporation. Amino acid incorporation into ribosomal proteins revealed several rapidly labeled components. When 3H-labeled amino acid incorporation was chased for 10 min with an excess of non-radioactive amino acids, several proteins reached at least 60% of the specific activity they showed after 150 min of chase. The time lapse between the onset of 3H-labeled amino acid incorporation and arrival at its plateau appeared to differ among various ribosomal proteins of a subunit, suggesting a heterogeneity in the pools of ribosomal proteins.", "contents": "In vivo isotope incorporation patterns into HeLa ribosomal proteins. When cells were incubated with L-[35S] methionine plus L-[Me-3H] methionine, it was found that at least four ribosomal proteins had 3H/35S ratios higher than the rest of the ribosomal proteins, suggesting that they were methylated. The rate of apparent methylation paralleled the rate of amino acid incorporation. Amino acid incorporation into ribosomal proteins revealed several rapidly labeled components. When 3H-labeled amino acid incorporation was chased for 10 min with an excess of non-radioactive amino acids, several proteins reached at least 60% of the specific activity they showed after 150 min of chase. The time lapse between the onset of 3H-labeled amino acid incorporation and arrival at its plateau appeared to differ among various ribosomal proteins of a subunit, suggesting a heterogeneity in the pools of ribosomal proteins."} {"id": "PMID:1260049", "title": "Isomerisation and conformation studies of (+)- and (-)6-hydroxy-5, 6-dihydrouridine.", "content": "(1) \"Uridine hydrates\" i.e. (+)- and (-)6-hydroxy-5, 6-dihydrouridine were formed under gamma irradiation in a deaerated aqueous solution of uridine. (2) The structures of two diastereoisomers were determined by spectroscopic measurements (infrared, ultraviolet and NMR) and verified by stereospecific synthesis; uridine hydrates were prepared by mild reduction of trans(+)- and (-)iodohydrins with acetic acid and zinc power. (3) The carbon 6 epimerisation of uridine hydrates 6R or 6S was performed in triated water (pH 5.5, 30 degrees C) and at the same time tritium incorporation on carbon 5 was noted. The mechanism of these reactions could be explained by the opening of the N1-C6 bond of the pyrimidine ring, followed by ketoenolisation reaction of carbons 4 and 5. (4) The 250 MHz NMR analysis has allowed us to determine the nucleoside conformations. Nucleosides had mainly the S(C2' endo) conformation. A slight preference of gauche-gauche (gg) rotamer of the exocyclic hydroxymethyl group was noted and the aglycone was in the anti conformation.", "contents": "Isomerisation and conformation studies of (+)- and (-)6-hydroxy-5, 6-dihydrouridine. (1) \"Uridine hydrates\" i.e. (+)- and (-)6-hydroxy-5, 6-dihydrouridine were formed under gamma irradiation in a deaerated aqueous solution of uridine. (2) The structures of two diastereoisomers were determined by spectroscopic measurements (infrared, ultraviolet and NMR) and verified by stereospecific synthesis; uridine hydrates were prepared by mild reduction of trans(+)- and (-)iodohydrins with acetic acid and zinc power. (3) The carbon 6 epimerisation of uridine hydrates 6R or 6S was performed in triated water (pH 5.5, 30 degrees C) and at the same time tritium incorporation on carbon 5 was noted. The mechanism of these reactions could be explained by the opening of the N1-C6 bond of the pyrimidine ring, followed by ketoenolisation reaction of carbons 4 and 5. (4) The 250 MHz NMR analysis has allowed us to determine the nucleoside conformations. Nucleosides had mainly the S(C2' endo) conformation. A slight preference of gauche-gauche (gg) rotamer of the exocyclic hydroxymethyl group was noted and the aglycone was in the anti conformation."} {"id": "PMID:1260050", "title": "Unmethylated DNA in mouse L cells. I. DNA fibre autoradiography.", "content": "Enzymatic methylation of DNA in mouse L cells has been studied using DNA fibre autoradiography to analyse the distribution of 5-methylcytosine in chromosomal DNA. The autoradiographic pattern of DNA labelled in the 5-methylcytosine is in several respects similar to the pattern of DNA replication. Two mean features are apparent: (1) the silver grains appear in well defined sections, and (2) the labelled sections are arranged in tandem along each DNA double helix. After a short pulse of radioactivity in the rate of growth of labeled sections in the pattern of DNA replication and the enzymatic methylation of DNA are identical. Unlike the replication pattern, DNA labeled during the S phase with L-[Me-3H] methionine is not completely labeled. There are distinct, 8-20 mum intervals in the autoradiographic pattern of this DNA. The length of these intervals may correspond to unmethylated sections of chromosomal DNA of about 23 to 58 kilo base pairs. These unmethylated sections of chromosomal DNA represent about 10% of the total genome.", "contents": "Unmethylated DNA in mouse L cells. I. DNA fibre autoradiography. Enzymatic methylation of DNA in mouse L cells has been studied using DNA fibre autoradiography to analyse the distribution of 5-methylcytosine in chromosomal DNA. The autoradiographic pattern of DNA labelled in the 5-methylcytosine is in several respects similar to the pattern of DNA replication. Two mean features are apparent: (1) the silver grains appear in well defined sections, and (2) the labelled sections are arranged in tandem along each DNA double helix. After a short pulse of radioactivity in the rate of growth of labeled sections in the pattern of DNA replication and the enzymatic methylation of DNA are identical. Unlike the replication pattern, DNA labeled during the S phase with L-[Me-3H] methionine is not completely labeled. There are distinct, 8-20 mum intervals in the autoradiographic pattern of this DNA. The length of these intervals may correspond to unmethylated sections of chromosomal DNA of about 23 to 58 kilo base pairs. These unmethylated sections of chromosomal DNA represent about 10% of the total genome."} {"id": "PMID:1260051", "title": "High molecular weight UMP-rich RNA of germinating wheat embryo.", "content": "The synthesis of a relatively homogeneous RNA fraction was observed in germinating wheat embryo. The fraction synthesised within the first 3 h of germination had a high molecular weight (approx. 2.10(6)) and a specific nucleotide composition. In particular, the UMP content was unusually high (47 mol%). The high UMP content resulted probably from the presence of UMP-rich regions within the newly-synthesised polynucleotide chain. Neither ribosomal nor transfer DNA sequences were transcribed at the same time. It is suggested that the newly-synthesised RNA fraction represents an mRNA precursor and is transcribed in the immediate response of wheat embryo to the environmental stimuli to germinate.", "contents": "High molecular weight UMP-rich RNA of germinating wheat embryo. The synthesis of a relatively homogeneous RNA fraction was observed in germinating wheat embryo. The fraction synthesised within the first 3 h of germination had a high molecular weight (approx. 2.10(6)) and a specific nucleotide composition. In particular, the UMP content was unusually high (47 mol%). The high UMP content resulted probably from the presence of UMP-rich regions within the newly-synthesised polynucleotide chain. Neither ribosomal nor transfer DNA sequences were transcribed at the same time. It is suggested that the newly-synthesised RNA fraction represents an mRNA precursor and is transcribed in the immediate response of wheat embryo to the environmental stimuli to germinate."} {"id": "PMID:1260052", "title": "Independent fluctuations of cytidine and adenosine diphosphate reductase activities in cultured Chinese hamster fibroblasts.", "content": "The activities of CDP and ADP reductases were determined throughout the cell cycle of Chinese hamster fibroblasts synchronized by partial deprivation of isoleucine. Both enzyme activities were increased in S phase as compared to G1 phase. CDP reductase increased about 8-fold while ADP reductase increased about 2.5-fold. The ratio of CDP to ADP reductase was 0.26 at the G1 and early S phases of the cell cycle; the ratio was increased to 0.83 by late S phase. Addition of actinomycin D or cycloheximide to cell cultures in G1 phase prevented the increase of both CDP and ADP reductases activities in the latter part of the cell cycle, but the ratio of the two activities was not affected. The ratio of CDP to ADP reductase activities varied from 0.8 to 3 in different populations of exponentially growing DON cells. These results show that CDP and ADP reductase activities vary independently in growing cells. The independent variation with cell growth of CDP and ADP reductases suggests important individual functions of the deoxynucleotides during the cell cycle apart from their common role as precursors of DNA synthesis.", "contents": "Independent fluctuations of cytidine and adenosine diphosphate reductase activities in cultured Chinese hamster fibroblasts. The activities of CDP and ADP reductases were determined throughout the cell cycle of Chinese hamster fibroblasts synchronized by partial deprivation of isoleucine. Both enzyme activities were increased in S phase as compared to G1 phase. CDP reductase increased about 8-fold while ADP reductase increased about 2.5-fold. The ratio of CDP to ADP reductase was 0.26 at the G1 and early S phases of the cell cycle; the ratio was increased to 0.83 by late S phase. Addition of actinomycin D or cycloheximide to cell cultures in G1 phase prevented the increase of both CDP and ADP reductases activities in the latter part of the cell cycle, but the ratio of the two activities was not affected. The ratio of CDP to ADP reductase activities varied from 0.8 to 3 in different populations of exponentially growing DON cells. These results show that CDP and ADP reductase activities vary independently in growing cells. The independent variation with cell growth of CDP and ADP reductases suggests important individual functions of the deoxynucleotides during the cell cycle apart from their common role as precursors of DNA synthesis."} {"id": "PMID:1260053", "title": "Distribution of membrane-bound and free ribosomes in growing yeast.", "content": "1. The distribution of membrane-bound and free ribosomes was investigated in stationary as well as in growing yeast cells. the relative amount of free ribosomes varies with the growth phase of the cell culture. During the duplication phases of the cell, relative maxima of free ribosomes can be found. However, the absolute amount of free ribosomes is fairly constant during the growth of the cells. 2. Membrane-bound ribosomes show lower polypeptide synthesis activity in a cell-free, poly (U)-dependent system than free ribosomes. 3. There is no difference in the distribution pattern of free and membrane-bound ribosomes in growing yeast cells of different ploidy. 4. A turnover between free and membrane-bound ribosomes is suggested to be in agreement with the hypothesis of Branes and Pogo ((1975) Eur. J. Biochem. 54, 317-328).", "contents": "Distribution of membrane-bound and free ribosomes in growing yeast. 1. The distribution of membrane-bound and free ribosomes was investigated in stationary as well as in growing yeast cells. the relative amount of free ribosomes varies with the growth phase of the cell culture. During the duplication phases of the cell, relative maxima of free ribosomes can be found. However, the absolute amount of free ribosomes is fairly constant during the growth of the cells. 2. Membrane-bound ribosomes show lower polypeptide synthesis activity in a cell-free, poly (U)-dependent system than free ribosomes. 3. There is no difference in the distribution pattern of free and membrane-bound ribosomes in growing yeast cells of different ploidy. 4. A turnover between free and membrane-bound ribosomes is suggested to be in agreement with the hypothesis of Branes and Pogo ((1975) Eur. J. Biochem. 54, 317-328)."} {"id": "PMID:1260054", "title": "Effect of the gel to liquid crystalline phase transition on the osmotic behaviour of phosphatidylcholine liposomes.", "content": "Aspects of osmotic properties of liposomes, prepared from synthetic lecithin, above, at and below the gel to liquid crystalline phase transition temperature are described. The experiments show that liposomal membranes with their lipids in the gel state are still permeable to water. The rate of water permeation changes drastically on passing the transition temperature. The water permeation has activation energies of 9.5 +/- 1.28 and 26.4 +/- 0.9 kcal/mol above and below the transition temperature, respectively, indicating that the diffusion processes take place by different mechanisms. With respect to the barrier properties of the liposomes in the vicinity of the transition temperature, the following conclusions can be made. (1) Studying the osmotic shrinkage of liposomes at a fixed temperature near the transition point, the experiments indicate that dimyristoyl phosphatidylcholine membranes are highly permeable to glucose under these conditions, where liquid and solid domains co-exist. Under the same conditions the osmotic experiments did not indicate a strong increase in glucose permeability of dipalmitoyl phosphatidylcholine membranes as compared to the situation above and below the transition temperature. (2) On the other hand, perturbations of the phase equilibrium by temperature varations resulted in a marked increase of the glucose permeation through dipalmitoyl phosphatidylcholine bilayers. Once a new phase equilibrium of liquid and solid regions is established the permeation rate of glucose is much less.", "contents": "Effect of the gel to liquid crystalline phase transition on the osmotic behaviour of phosphatidylcholine liposomes. Aspects of osmotic properties of liposomes, prepared from synthetic lecithin, above, at and below the gel to liquid crystalline phase transition temperature are described. The experiments show that liposomal membranes with their lipids in the gel state are still permeable to water. The rate of water permeation changes drastically on passing the transition temperature. The water permeation has activation energies of 9.5 +/- 1.28 and 26.4 +/- 0.9 kcal/mol above and below the transition temperature, respectively, indicating that the diffusion processes take place by different mechanisms. With respect to the barrier properties of the liposomes in the vicinity of the transition temperature, the following conclusions can be made. (1) Studying the osmotic shrinkage of liposomes at a fixed temperature near the transition point, the experiments indicate that dimyristoyl phosphatidylcholine membranes are highly permeable to glucose under these conditions, where liquid and solid domains co-exist. Under the same conditions the osmotic experiments did not indicate a strong increase in glucose permeability of dipalmitoyl phosphatidylcholine membranes as compared to the situation above and below the transition temperature. (2) On the other hand, perturbations of the phase equilibrium by temperature varations resulted in a marked increase of the glucose permeation through dipalmitoyl phosphatidylcholine bilayers. Once a new phase equilibrium of liquid and solid regions is established the permeation rate of glucose is much less."} {"id": "PMID:1260056", "title": "Microviscosity parameters and protein mobility in biological membranes.", "content": "A fluorescence polarization technique with 1,6-diphenyl 1,3,5-hexatriene as a probe were employed to determine the microviscosity, n, in liposomes and biological membranes of different cholesterol to phospholipid mol ratio. From the temperature profile of n the flow activation energy, deltaE, and the unit flow volume, V, were derived. The increase of cholesterol/phospholipid ratio in liposomes is followed by a marked increase in n and a decrease in both deltaE and V. Liposomes of the same phospholipid composition as human erythrocyte membranes display in the extreme cases of cholesterol/phospholipid ratios 0 and 1.4 the values of n(25 degrees C) = 1.8 and 9.1 P, and deltaE = 15.0 and 6.5 kcal/mol, respectively. For most membranes studied the fluorescence polarization characteristics and the corresponding n values are similar to those obtained with these liposomes when the cholesterol/phospholipid level of the liposomes and the membranes were the same. However, unlike in liposomes deltaE of all membranes is in the narrow range of 6.5-8.5 kcal/mol, regardless of its cholesterol/phospholipid level. It is plausible that this is a general characteristic of biological membranes which originates from the vertical movement of membrane proteins to an equilibrium position which maintains constant deltaE and V values. This type of movement should affect the interrelation between lipid fluidity and protein mobility. Lipid microviscosity and the degree of rotational mobility of concanavalin A receptor sites in cell membranes were therefore determined. The examined cells were normal and malignant fibroblasts, as an example of cells that form solid tumours in vivo, and normal and malignant lymphocytes, as an example of cells that form ascites tumours in vivo. In both cell systems, opposite correlations between the lipid fluidity and the mobility of concanavalin A receptors were observed. In the fibroblasts the malignant cells possess a lower lipid fluidity but a higher receptor mobility, whereas in the lymphocytes the malignant cells possess a higher lipid fluidity but a lower receptor mobility. Thus, in these cell systems the degree of rotational mobility of concanavalin A receptors increases upon decreasing the lipid fluidity and decreases upon increasing the fluidity of the lipid core. This dynamic feature is in line with the above proposal according to which the concanavalin A receptor sites become more exposed to the aqueous surrounding upon increasing the microviscosity of the lipid layer and vice versa.", "contents": "Microviscosity parameters and protein mobility in biological membranes. A fluorescence polarization technique with 1,6-diphenyl 1,3,5-hexatriene as a probe were employed to determine the microviscosity, n, in liposomes and biological membranes of different cholesterol to phospholipid mol ratio. From the temperature profile of n the flow activation energy, deltaE, and the unit flow volume, V, were derived. The increase of cholesterol/phospholipid ratio in liposomes is followed by a marked increase in n and a decrease in both deltaE and V. Liposomes of the same phospholipid composition as human erythrocyte membranes display in the extreme cases of cholesterol/phospholipid ratios 0 and 1.4 the values of n(25 degrees C) = 1.8 and 9.1 P, and deltaE = 15.0 and 6.5 kcal/mol, respectively. For most membranes studied the fluorescence polarization characteristics and the corresponding n values are similar to those obtained with these liposomes when the cholesterol/phospholipid level of the liposomes and the membranes were the same. However, unlike in liposomes deltaE of all membranes is in the narrow range of 6.5-8.5 kcal/mol, regardless of its cholesterol/phospholipid level. It is plausible that this is a general characteristic of biological membranes which originates from the vertical movement of membrane proteins to an equilibrium position which maintains constant deltaE and V values. This type of movement should affect the interrelation between lipid fluidity and protein mobility. Lipid microviscosity and the degree of rotational mobility of concanavalin A receptor sites in cell membranes were therefore determined. The examined cells were normal and malignant fibroblasts, as an example of cells that form solid tumours in vivo, and normal and malignant lymphocytes, as an example of cells that form ascites tumours in vivo. In both cell systems, opposite correlations between the lipid fluidity and the mobility of concanavalin A receptors were observed. In the fibroblasts the malignant cells possess a lower lipid fluidity but a higher receptor mobility, whereas in the lymphocytes the malignant cells possess a higher lipid fluidity but a lower receptor mobility. Thus, in these cell systems the degree of rotational mobility of concanavalin A receptors increases upon decreasing the lipid fluidity and decreases upon increasing the fluidity of the lipid core. This dynamic feature is in line with the above proposal according to which the concanavalin A receptor sites become more exposed to the aqueous surrounding upon increasing the microviscosity of the lipid layer and vice versa."} {"id": "PMID:1260057", "title": "Structural and membrane modifying properties of suzukacillin, a peptide antibiotic related to alamethicin. Part A. Sequence and conformation.", "content": "The primary structure and conformation of the polypeptide antibiotic suzukacillin A are investigated. Suzukacillin A is isolated from the Trichoderma viride strain 1037 and exhibits membrane modifying and lysing properties similar to those of alamethicin. A combined gas chromatographic mass spectrometric analysis of the trifluoroacetylated peptide methyl esters of partial hydrolysates revealed a tentative sequence of 23 residues including 10 2-methylalanines and one phenylalaninol, which shows many fragments known from alamethicin: Ac-Aib-Pro-Val-Aib-Val-Ala-Aib-Ala-Aib-Aib-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-Glu(Pheol)-Gln-OH. All chiral amino acids and phenylalainol have L-configuration. Ultraviolet and infrared spectroscopy, circular dichroism in various solvents and in particular 13C nuclear magnetic resonance have been used for a comparative study of suzukacillin with alamethicin. Suzukacillin has a partially alpha-helical structure and the helix content increases largely from polar to lipophilic solvents. Suzukacillin aggregates more strongly than alamethicin in aqueous medis due to a longer alpha-helical part and higher number of aliphatic residues. A part of the alpha-helix is exceptionally stabilized due to 2-methylalanine residues shielding the peptide bonds from interactions with polar solvents. In lipophilic solvents and lecithin vesicles particularly large temperature induced reductions of the high alpha-helix content are found for alamethicin. Suzukacillin shows similar temperature coefficients in lipophilic media, however, in contrast to alamethicin a more linear change in intensity of the Cotton effects is observed.", "contents": "Structural and membrane modifying properties of suzukacillin, a peptide antibiotic related to alamethicin. Part A. Sequence and conformation. The primary structure and conformation of the polypeptide antibiotic suzukacillin A are investigated. Suzukacillin A is isolated from the Trichoderma viride strain 1037 and exhibits membrane modifying and lysing properties similar to those of alamethicin. A combined gas chromatographic mass spectrometric analysis of the trifluoroacetylated peptide methyl esters of partial hydrolysates revealed a tentative sequence of 23 residues including 10 2-methylalanines and one phenylalaninol, which shows many fragments known from alamethicin: Ac-Aib-Pro-Val-Aib-Val-Ala-Aib-Ala-Aib-Aib-Gln-Aib-Leu-Aib-Gly-Leu-Aib-Pro-Val-Aib-Aib-Glu(Pheol)-Gln-OH. All chiral amino acids and phenylalainol have L-configuration. Ultraviolet and infrared spectroscopy, circular dichroism in various solvents and in particular 13C nuclear magnetic resonance have been used for a comparative study of suzukacillin with alamethicin. Suzukacillin has a partially alpha-helical structure and the helix content increases largely from polar to lipophilic solvents. Suzukacillin aggregates more strongly than alamethicin in aqueous medis due to a longer alpha-helical part and higher number of aliphatic residues. A part of the alpha-helix is exceptionally stabilized due to 2-methylalanine residues shielding the peptide bonds from interactions with polar solvents. In lipophilic solvents and lecithin vesicles particularly large temperature induced reductions of the high alpha-helix content are found for alamethicin. Suzukacillin shows similar temperature coefficients in lipophilic media, however, in contrast to alamethicin a more linear change in intensity of the Cotton effects is observed."} {"id": "PMID:1260058", "title": "Structural and membrane modifying porperties of suzukacillin, a peptide antibiotic related to alamethicin. Part B. Pore formation in black lipid films.", "content": "Suzukacillin, a polypeptide consisting of presumably 23 amino acids and 1 phenylalaninol, is produced by a Trichoderma viride strain No. 1037 and it can be isolated from the culture medium. It shows membrane-modifying properties similar to those of alamethicin. Discrete condustance fluctuations indicate the formation of oligomer pores of varying diameter. On the basis of voltage jump relaxation experiments evidence is given that the dimer is the nucleation state from which pore formation starts and the oligomer disappears. According to the voltage-current characteristics, voltage-dependent and voltage-independent conductances are observed. A slow process is involved, which can be interpreted as a change in the equilibrium distribution between different conformations of the suzukacillin monomer at the membrane interphase. This change results from its interaction with the lipid matrix. Differences in experimental observations between suzukacillin and alamethicin are attributed to the relatively larger alpha-helix and higher number of aliphatic side chains of the suzukacillin monomer and to a more intense interaction with the lipid membrane. This leads to a higher probability of forming dimers from monomers and to the occurrence of \"inactivation\".", "contents": "Structural and membrane modifying porperties of suzukacillin, a peptide antibiotic related to alamethicin. Part B. Pore formation in black lipid films. Suzukacillin, a polypeptide consisting of presumably 23 amino acids and 1 phenylalaninol, is produced by a Trichoderma viride strain No. 1037 and it can be isolated from the culture medium. It shows membrane-modifying properties similar to those of alamethicin. Discrete condustance fluctuations indicate the formation of oligomer pores of varying diameter. On the basis of voltage jump relaxation experiments evidence is given that the dimer is the nucleation state from which pore formation starts and the oligomer disappears. According to the voltage-current characteristics, voltage-dependent and voltage-independent conductances are observed. A slow process is involved, which can be interpreted as a change in the equilibrium distribution between different conformations of the suzukacillin monomer at the membrane interphase. This change results from its interaction with the lipid matrix. Differences in experimental observations between suzukacillin and alamethicin are attributed to the relatively larger alpha-helix and higher number of aliphatic side chains of the suzukacillin monomer and to a more intense interaction with the lipid membrane. This leads to a higher probability of forming dimers from monomers and to the occurrence of \"inactivation\"."} {"id": "PMID:1260059", "title": "Hydrolysis of phosphatidylcholine liposomes by phospholipases A2. Effects of the local anesthetic dibucaine.", "content": "(1) Dibucaine evokes a downward shift in the phase transition temperature of saturated phosphatidylcholines, while it also affects the pretransition. (2) The binding of dibucaine to phosphatidylcholine liposomes increases sharply when the lipid is transformed from the gel phase to the liquid-crystalline phase. (3) The activity of Naja naja phospholipase A2 towards dimyristoyl phosphatidylcholine liposomes is either stimulated or inhibited by dibucaine, depending on whether the substrate is in the gel or the liquid-crystalline state, respectively, whereas the activity of pancreatic phospholipase A2 is inhibited by the anesthetic irrespective of the physical state of the substrate. This observation is further substantiated by the results of studies on liposomes prepared from mixtures of dimyristoyl and dipalmitoyl phosphatidylcholine or dilauroyl and distearoyl phosphatidylcholine. (4) The uptake of dibucaine by positively charged liposomes composed of phosphatidylcholine and stearylamine is considerably reduced in comparison with pure phosphatidylcholine liposomes. This decrease is paralleled by a reduction of the inhibitory and stimulatory effects of dibucaine on the hydrolysis of such liposomes by pancreatic and Naja naja phospholipase, respectively. (5) The inhibitory action of dibucaine towards the pancreatic phospholipase is lowered by increasing CaCl2 concentrations. This reduction is accompanied by a decreased uptake of anesthetic by the liposomes.", "contents": "Hydrolysis of phosphatidylcholine liposomes by phospholipases A2. Effects of the local anesthetic dibucaine. (1) Dibucaine evokes a downward shift in the phase transition temperature of saturated phosphatidylcholines, while it also affects the pretransition. (2) The binding of dibucaine to phosphatidylcholine liposomes increases sharply when the lipid is transformed from the gel phase to the liquid-crystalline phase. (3) The activity of Naja naja phospholipase A2 towards dimyristoyl phosphatidylcholine liposomes is either stimulated or inhibited by dibucaine, depending on whether the substrate is in the gel or the liquid-crystalline state, respectively, whereas the activity of pancreatic phospholipase A2 is inhibited by the anesthetic irrespective of the physical state of the substrate. This observation is further substantiated by the results of studies on liposomes prepared from mixtures of dimyristoyl and dipalmitoyl phosphatidylcholine or dilauroyl and distearoyl phosphatidylcholine. (4) The uptake of dibucaine by positively charged liposomes composed of phosphatidylcholine and stearylamine is considerably reduced in comparison with pure phosphatidylcholine liposomes. This decrease is paralleled by a reduction of the inhibitory and stimulatory effects of dibucaine on the hydrolysis of such liposomes by pancreatic and Naja naja phospholipase, respectively. (5) The inhibitory action of dibucaine towards the pancreatic phospholipase is lowered by increasing CaCl2 concentrations. This reduction is accompanied by a decreased uptake of anesthetic by the liposomes."} {"id": "PMID:1260061", "title": "Lateral diffusion of concanavalin A receptors in the plasma membrane of mouse fibroblasts.", "content": "Lateral diffusion of receptors binding fluorescein labeled concanavalin A and its succinylated derivative has been measured by bleaching portions of the labeled surface and following return of fluorescence to the bleached spot. Binding of either concanavalin A or its succinylated derivative causes restriction of mobility of the surface receptors for this lectin. The degree of restriction is a function of time after binding the lectin.", "contents": "Lateral diffusion of concanavalin A receptors in the plasma membrane of mouse fibroblasts. Lateral diffusion of receptors binding fluorescein labeled concanavalin A and its succinylated derivative has been measured by bleaching portions of the labeled surface and following return of fluorescence to the bleached spot. Binding of either concanavalin A or its succinylated derivative causes restriction of mobility of the surface receptors for this lectin. The degree of restriction is a function of time after binding the lectin."} {"id": "PMID:1260062", "title": "Studies on the transport of aliphatic glucosides by hamster small intestine in vitro.", "content": "It has been found (1) that glucosides with a long alkyl chain (2-18 carbon atoms) as the aglycone can be transported by carrier-mediated processes in the hamster small intestine in vitro, (2) that these glucosides interact with the glucose carrier, and (3) that they compete with glucose and analogs for the binding to the carrier. The are Na+- and phlorizin-insensitive components of uptake for the long chain alkyl glucosides which suggest additional interactions or uptake processes.", "contents": "Studies on the transport of aliphatic glucosides by hamster small intestine in vitro. It has been found (1) that glucosides with a long alkyl chain (2-18 carbon atoms) as the aglycone can be transported by carrier-mediated processes in the hamster small intestine in vitro, (2) that these glucosides interact with the glucose carrier, and (3) that they compete with glucose and analogs for the binding to the carrier. The are Na+- and phlorizin-insensitive components of uptake for the long chain alkyl glucosides which suggest additional interactions or uptake processes."} {"id": "PMID:1260063", "title": "Preparation of chick brain synaptosomes and synaptosomal membranes.", "content": "A method is described for the preparation of synaptosomes and synaptosomal membranes from chicken brain. Procedures for isolating rat synaptosomal membranes could not be used directly; several modifications of existing procedures are reported. Purity of the subcellular and subsynaptosomal fractions was monitored by electron microscopy and measurements of ferrocytochrome c: oxygen oxidoreductase (EC 1.9.3.)), monoamine: oxygen oxidoreductase (deaminating) EC 1.4.3.4), rotenone-insensitive NADH: cytochrome c oxidoreductase (EC 1.6.99.3), NADPH: cytochrome c oxidoreductase (EC 1.6.99.1), orthophosphoric monoester phosphohydrolase (EC 3.1.3.2), ATP phosphohydrolase (EC 3.6.1.4), and levels of RNA. Microsomes are the main contaminant of the synaptosomal membrane fraction. Mitochondrial and lysosomal enzymes occur in lesser amounts. No myelin contamination was observed. Marker enzymes for contaminants suggest that these synaptosomal membranes are as pure as membranes described by others, and the specific activity of a neuronal membrane marker, (Na+ -K+)-activated ATPase, is as high as other preparations. Levels of this enzyme in the membrane fraction are enriched 13-fold over homogenate ATPase levels.", "contents": "Preparation of chick brain synaptosomes and synaptosomal membranes. A method is described for the preparation of synaptosomes and synaptosomal membranes from chicken brain. Procedures for isolating rat synaptosomal membranes could not be used directly; several modifications of existing procedures are reported. Purity of the subcellular and subsynaptosomal fractions was monitored by electron microscopy and measurements of ferrocytochrome c: oxygen oxidoreductase (EC 1.9.3.)), monoamine: oxygen oxidoreductase (deaminating) EC 1.4.3.4), rotenone-insensitive NADH: cytochrome c oxidoreductase (EC 1.6.99.3), NADPH: cytochrome c oxidoreductase (EC 1.6.99.1), orthophosphoric monoester phosphohydrolase (EC 3.1.3.2), ATP phosphohydrolase (EC 3.6.1.4), and levels of RNA. Microsomes are the main contaminant of the synaptosomal membrane fraction. Mitochondrial and lysosomal enzymes occur in lesser amounts. No myelin contamination was observed. Marker enzymes for contaminants suggest that these synaptosomal membranes are as pure as membranes described by others, and the specific activity of a neuronal membrane marker, (Na+ -K+)-activated ATPase, is as high as other preparations. Levels of this enzyme in the membrane fraction are enriched 13-fold over homogenate ATPase levels."} {"id": "PMID:1260064", "title": "Stimulation of sodium and calcium uptake by scorpion toxin in chick embryo heart cells.", "content": "Scorpion toxins, the basic miniproteins of scorpion venom, stimulated the passive uptake of Na+ and Ca2+ in chick embryo heart cells. Half-maximum stimulation was obtained for 20-30 nM Na+ and 40-50 nM Ca2+. Scorpion toxin-activated Na+ and Ca2+ uptakes were fully inhibited by tetrodotoxin, a specific inhibitor of the action potential Na+ ionophore in excitable membranes. Half-maximum inhibition was obtained with the same concentration of tetrodotoxin (10 nM) for both Na+ and Ca2+. Scorpion toxin-stimulated Ca2+ uptake was dependent on extracellular Na+ concentration and was not inhibited by Ca2+ channel blocking drugs which are inactive on heart cell action potential. Thus, in heart cells scorpion toxin affects the passive Ca2+ transport, which is coupled to passive Na+ ionphore. Other results suggest that (1) tetrodotoxin and scorpion toxin bind to different sites of the sarcolemma and (2) binding of scorpion toxin to its specific sites may unmask latent tetrodotoxin - sensitive fast channels.", "contents": "Stimulation of sodium and calcium uptake by scorpion toxin in chick embryo heart cells. Scorpion toxins, the basic miniproteins of scorpion venom, stimulated the passive uptake of Na+ and Ca2+ in chick embryo heart cells. Half-maximum stimulation was obtained for 20-30 nM Na+ and 40-50 nM Ca2+. Scorpion toxin-activated Na+ and Ca2+ uptakes were fully inhibited by tetrodotoxin, a specific inhibitor of the action potential Na+ ionophore in excitable membranes. Half-maximum inhibition was obtained with the same concentration of tetrodotoxin (10 nM) for both Na+ and Ca2+. Scorpion toxin-stimulated Ca2+ uptake was dependent on extracellular Na+ concentration and was not inhibited by Ca2+ channel blocking drugs which are inactive on heart cell action potential. Thus, in heart cells scorpion toxin affects the passive Ca2+ transport, which is coupled to passive Na+ ionphore. Other results suggest that (1) tetrodotoxin and scorpion toxin bind to different sites of the sarcolemma and (2) binding of scorpion toxin to its specific sites may unmask latent tetrodotoxin - sensitive fast channels."} {"id": "PMID:1260066", "title": "Inorganic polyphosphate as an integral part of alkaline phosphatase preparations.", "content": "Alkaline phosphatase (from chicken intestinal sources) was shown to contain a considerable amount of polyanionic phosphorus which was released by basic digestion. The polyanionic phosphorus of alkaline phosphatase is not associated with protein or polyalcohols and does not exhibit a visible or ultraviolet absorption spectrum. Alkaline phosphatase and abiogenic inorganic polyphosphate were found to incorporate 32P-orthophosphate under similar experimental conditions. It has been previously reported that this enzyme will incorporate 32P-orthophosphate into its protein phosphoserine without the apparent concomitant utilization of an energy source. This reported phosphorylation was immediately reversible upon dilution of the phosphorylated enzyme with unlabelled orthophosphate, which indicates that the initial phosphorylation was an exchange reaction. These observations suggest that this polyanionic phosphorus from alkaline phosphatase may be inorganic polyphosphate.", "contents": "Inorganic polyphosphate as an integral part of alkaline phosphatase preparations. Alkaline phosphatase (from chicken intestinal sources) was shown to contain a considerable amount of polyanionic phosphorus which was released by basic digestion. The polyanionic phosphorus of alkaline phosphatase is not associated with protein or polyalcohols and does not exhibit a visible or ultraviolet absorption spectrum. Alkaline phosphatase and abiogenic inorganic polyphosphate were found to incorporate 32P-orthophosphate under similar experimental conditions. It has been previously reported that this enzyme will incorporate 32P-orthophosphate into its protein phosphoserine without the apparent concomitant utilization of an energy source. This reported phosphorylation was immediately reversible upon dilution of the phosphorylated enzyme with unlabelled orthophosphate, which indicates that the initial phosphorylation was an exchange reaction. These observations suggest that this polyanionic phosphorus from alkaline phosphatase may be inorganic polyphosphate."} {"id": "PMID:1260067", "title": "Effects of sex hormones and of pregnancy on the selenium metabolism.", "content": "In order to obtain information about the hormonal regulation of the selenium metabolism, the element level in the blood serum of rats was determined by means of neutron activation analysis after administration of sex hormones and during pregnancy. While the decreases in the mean selenium concentrations found after the treatment with progesterone and progesterone + estrone were too low to enable us to establish response patterns, marked changes were observed in the serum of gravid rats. Here the selenium level dropped significantly (P less than 0.001) by 25% between the 10th and 15th day of gestation.", "contents": "Effects of sex hormones and of pregnancy on the selenium metabolism. In order to obtain information about the hormonal regulation of the selenium metabolism, the element level in the blood serum of rats was determined by means of neutron activation analysis after administration of sex hormones and during pregnancy. While the decreases in the mean selenium concentrations found after the treatment with progesterone and progesterone + estrone were too low to enable us to establish response patterns, marked changes were observed in the serum of gravid rats. Here the selenium level dropped significantly (P less than 0.001) by 25% between the 10th and 15th day of gestation."} {"id": "PMID:1260068", "title": "Biological effects of the enhanced excretion of zinc after calcium diethylenetriaminepentaacetate chelation therapy.", "content": "An enhanced, uncompensated excretion of zinc may be responsible for unwanted side-effects that could develop after prolonged chelation therapy with calcium diethylenetriaminepentaacetate (Ca-DTPA). As a preliminary means of defining \"potential toxicity\" within this hypothesis, the \"normal\" concentration range of Zn++ excreted in the urine of three adult female baboons was measured on a daily basis; changes in urinary Zn++ excretion were then quantitated as a function of the injection time and dose of the chelating agent Na3(Ca-DTPA) originally administered to enhance the excretion of 241Am from the body. In addition, the inhibitory action of the chelator compound on the activity of a specific metalloenzyme system, erythrocytic aminolevulinic acid dehydratase (ALAD), which requires Zn++ as a co-factor, has been determined as a measure of a specific biological effect. It was found that whenever the concentration of Zn++ in urine was above 2 mug/ml (or greater than approximately four times the \"normal\" urinary excretion level), the activity of ALAD dropped below 250 nmol PBG/ml RBC/hr or approximately one-half the mean \"normal\" activity value for this primate species.", "contents": "Biological effects of the enhanced excretion of zinc after calcium diethylenetriaminepentaacetate chelation therapy. An enhanced, uncompensated excretion of zinc may be responsible for unwanted side-effects that could develop after prolonged chelation therapy with calcium diethylenetriaminepentaacetate (Ca-DTPA). As a preliminary means of defining \"potential toxicity\" within this hypothesis, the \"normal\" concentration range of Zn++ excreted in the urine of three adult female baboons was measured on a daily basis; changes in urinary Zn++ excretion were then quantitated as a function of the injection time and dose of the chelating agent Na3(Ca-DTPA) originally administered to enhance the excretion of 241Am from the body. In addition, the inhibitory action of the chelator compound on the activity of a specific metalloenzyme system, erythrocytic aminolevulinic acid dehydratase (ALAD), which requires Zn++ as a co-factor, has been determined as a measure of a specific biological effect. It was found that whenever the concentration of Zn++ in urine was above 2 mug/ml (or greater than approximately four times the \"normal\" urinary excretion level), the activity of ALAD dropped below 250 nmol PBG/ml RBC/hr or approximately one-half the mean \"normal\" activity value for this primate species."} {"id": "PMID:1260069", "title": "Micellar effects upon the reaction of cobalt complexes with alkyl halides.", "content": "The reactions of the cobalozime Co (DH)-2 and the related Co(DOH)DOpn0 are strongly catalyzed by cationic micelles of cetyltrimethylammonium bromide (CTABr). The rate enhancements for the cobaloxime reaction and for that of Co (DOH)DOpn0 (in parentheses) are: EtBr approximately 1 (8.5); n-C5H11Cl, 220 (200); ClCH2CO-2, 420 (173); ClCH2CH2CO-2, 373. Anionic micelles of sodium lauryl sulfate inhibit the reaction of Co(DOH)DOpn0 with ClCH2CO-2, but do not affect that with n-C5H11Cl. The reactions of Co(DOH)DOpn0, like those of the cobaloxime are SN2 displacements and in the absence of surfactant in MeOH n-PrBr is more reactive than iso-PrBr.", "contents": "Micellar effects upon the reaction of cobalt complexes with alkyl halides. The reactions of the cobalozime Co (DH)-2 and the related Co(DOH)DOpn0 are strongly catalyzed by cationic micelles of cetyltrimethylammonium bromide (CTABr). The rate enhancements for the cobaloxime reaction and for that of Co (DOH)DOpn0 (in parentheses) are: EtBr approximately 1 (8.5); n-C5H11Cl, 220 (200); ClCH2CO-2, 420 (173); ClCH2CH2CO-2, 373. Anionic micelles of sodium lauryl sulfate inhibit the reaction of Co(DOH)DOpn0 with ClCH2CO-2, but do not affect that with n-C5H11Cl. The reactions of Co(DOH)DOpn0, like those of the cobaloxime are SN2 displacements and in the absence of surfactant in MeOH n-PrBr is more reactive than iso-PrBr."} {"id": "PMID:1260070", "title": "Use of pattern recognition to classify beef cardiovascular tissues on the basis of their trace metal compositions.", "content": "The pattern recognition procedure of discriminant analysis has been used to characterize the trace metal profiles created by the concentrations of 8 trace metals in 15 anatomic sites of beef heart tissue. Metals analyzed were copper, tin, lead, molybdenum, strontium, cesium, barium, and aluminum. Anatomic sites sampled included main pulmonary artery, aorta, mitral and tricuspid valves, left and right coronary arteries, os cordis, right atrium, left atrial appendage, crista supraventricularis, left bundle branch, free wall of the right and left ventricles, interventricular septum, and papillary muscle of the left ventricle. The striking features of the data were: (1) All specimens of the mitral valve, tricuspid valve, and os cordis were ambiguously described by their trace metal profiles; (2) the four blood vessels constituted two groups of two tissues each (aorta, main pulmonary artery; left and right coronary arteries); (3) tissues derived from ordinary and specialized myocardium were quite different from blood vessels, heart valves and os cordis. Using these profiles, 85% of the specimens analyzed were correctly classified by discriminant analysis with respect to their anatomic origin.", "contents": "Use of pattern recognition to classify beef cardiovascular tissues on the basis of their trace metal compositions. The pattern recognition procedure of discriminant analysis has been used to characterize the trace metal profiles created by the concentrations of 8 trace metals in 15 anatomic sites of beef heart tissue. Metals analyzed were copper, tin, lead, molybdenum, strontium, cesium, barium, and aluminum. Anatomic sites sampled included main pulmonary artery, aorta, mitral and tricuspid valves, left and right coronary arteries, os cordis, right atrium, left atrial appendage, crista supraventricularis, left bundle branch, free wall of the right and left ventricles, interventricular septum, and papillary muscle of the left ventricle. The striking features of the data were: (1) All specimens of the mitral valve, tricuspid valve, and os cordis were ambiguously described by their trace metal profiles; (2) the four blood vessels constituted two groups of two tissues each (aorta, main pulmonary artery; left and right coronary arteries); (3) tissues derived from ordinary and specialized myocardium were quite different from blood vessels, heart valves and os cordis. Using these profiles, 85% of the specimens analyzed were correctly classified by discriminant analysis with respect to their anatomic origin."} {"id": "PMID:1260071", "title": "Magnetic circular dichroism on the reversible oxygenation of dimethylmesoporphyrin-IX-atopyridinecobalt (II).", "content": "The magnetic circular dichroism spectra were measured for the dimethylmesoporphyrin-IX-atocobalt complexes. As expected dimethylmesoporphyrin-IX-atocobalt (III) and its pyridine complex exhibited the MCD for a typical D4h metalloporphyrins. Dimethylmesoporphyrin-IX-atocobalt (II) and its pyridine complex showed a paramagnetic effect on the MCD especially in the Soret region. A very atypical Soret MCD for the oxygenated dimethylmesoporphyrin-IX-atopyridinecobalt (II) was attributed to the existence of a CT band associated with oxygen from the similarity to the MCD for oxymyoglobin. Temperature-dependent MCD change for the cobalt (II) oxygen complex revealed the reversible oxygen binding to dimethylmesoporphyrin-IX-atopyridinecobalt (II) with KO2 of 3.2 X 10(-3) in (mmHg)-1 at 228 degrees K.", "contents": "Magnetic circular dichroism on the reversible oxygenation of dimethylmesoporphyrin-IX-atopyridinecobalt (II). The magnetic circular dichroism spectra were measured for the dimethylmesoporphyrin-IX-atocobalt complexes. As expected dimethylmesoporphyrin-IX-atocobalt (III) and its pyridine complex exhibited the MCD for a typical D4h metalloporphyrins. Dimethylmesoporphyrin-IX-atocobalt (II) and its pyridine complex showed a paramagnetic effect on the MCD especially in the Soret region. A very atypical Soret MCD for the oxygenated dimethylmesoporphyrin-IX-atopyridinecobalt (II) was attributed to the existence of a CT band associated with oxygen from the similarity to the MCD for oxymyoglobin. Temperature-dependent MCD change for the cobalt (II) oxygen complex revealed the reversible oxygen binding to dimethylmesoporphyrin-IX-atopyridinecobalt (II) with KO2 of 3.2 X 10(-3) in (mmHg)-1 at 228 degrees K."} {"id": "PMID:1260072", "title": "\"Flooding in vivo\" during the circadian phase of minimal cortisol secretion: anxiety and therapeutic success without adrenal cortical activation.", "content": "Seven patients with maximally severe phobias for physical objects were treated by \"flooding in vivo\", i.e. live confrontation with the feared object. Each reported to the laboratory for 3 hr on five separate occasions, all in the early evening during the circadian phase of minimal adrenal cortical activity. At 20-min intervals during each session, blood was taken for cortisol assay, and anxiety was self-rated on a scale of 0 to 100. Treatment was carried out during the 2nd hr of the third and fourth sessions. The remaining time provided control observations. By behavioral and subjective criteria, the treatment hours produced very intense anxiety. However, they failed to evaluate plasma cortisol levels. The remission of the phobias was 100%. Anxiety, even when intense and dramatic, does not necessarily activate the adrenal cortex, and an adrenal \"stress\" response is not necessary for the therapeutic effect.", "contents": "\"Flooding in vivo\" during the circadian phase of minimal cortisol secretion: anxiety and therapeutic success without adrenal cortical activation. Seven patients with maximally severe phobias for physical objects were treated by \"flooding in vivo\", i.e. live confrontation with the feared object. Each reported to the laboratory for 3 hr on five separate occasions, all in the early evening during the circadian phase of minimal adrenal cortical activity. At 20-min intervals during each session, blood was taken for cortisol assay, and anxiety was self-rated on a scale of 0 to 100. Treatment was carried out during the 2nd hr of the third and fourth sessions. The remaining time provided control observations. By behavioral and subjective criteria, the treatment hours produced very intense anxiety. However, they failed to evaluate plasma cortisol levels. The remission of the phobias was 100%. Anxiety, even when intense and dramatic, does not necessarily activate the adrenal cortex, and an adrenal \"stress\" response is not necessary for the therapeutic effect."} {"id": "PMID:1260075", "title": "Heritable factors in the severity of affective illness.", "content": "A review of clinical experience with 163 patients with primary affective disorder indicates that patients with a history characterized by recurrent depression interspersed with periods of hypomania (bipolar II) may have clinical courses that are distinguishable from bipolar I (depression with histories of mania) or unipolar patients. A prior history of suicide attempt and suicide after discharge from the research unit were most frequent among bipolar II patients. The family histories of bipolar I and bipolar II patients revealed similarly increased morbid risks for bipolar illness, whereas no bipolar illness was found in the first-degree relatives of unipolar patients. The suggestion that patients classified as bipolar II be separately considered in future studies of affective disorder is discussed.", "contents": "Heritable factors in the severity of affective illness. A review of clinical experience with 163 patients with primary affective disorder indicates that patients with a history characterized by recurrent depression interspersed with periods of hypomania (bipolar II) may have clinical courses that are distinguishable from bipolar I (depression with histories of mania) or unipolar patients. A prior history of suicide attempt and suicide after discharge from the research unit were most frequent among bipolar II patients. The family histories of bipolar I and bipolar II patients revealed similarly increased morbid risks for bipolar illness, whereas no bipolar illness was found in the first-degree relatives of unipolar patients. The suggestion that patients classified as bipolar II be separately considered in future studies of affective disorder is discussed."} {"id": "PMID:1260076", "title": "Assortative mating in primary affective disorder.", "content": "Psychiatric illness in spouses of patients with primary affective disorder was determined and compared to psychiatric illness in spouses of a nonpsychiatrically ill control group. An increase in affective illness in wives of bipolar male patients with affective disorder was found. There was no increase in affective illness among husbands of female patients. Marital status of these patients was evaluated and the percentages of patients who had never married or who had married but had ever been divorced or separated were similar to control data. Several of the marriages were quite stable over long time periods in spite of the severe recurrent affective illness experienced by these patients.", "contents": "Assortative mating in primary affective disorder. Psychiatric illness in spouses of patients with primary affective disorder was determined and compared to psychiatric illness in spouses of a nonpsychiatrically ill control group. An increase in affective illness in wives of bipolar male patients with affective disorder was found. There was no increase in affective illness among husbands of female patients. Marital status of these patients was evaluated and the percentages of patients who had never married or who had married but had ever been divorced or separated were similar to control data. Several of the marriages were quite stable over long time periods in spite of the severe recurrent affective illness experienced by these patients."} {"id": "PMID:1260077", "title": "Uptake of 3,4-dimethoxyphenylethylamine-1-14C (14C-DMPEA) by rat tissues in vitro.", "content": "Rat heart and spleen slices were incubated with 3,4-dimethoxyphenylethylamine-1-14C(14C-DMPEA) in Krebs medium at 37 C. At the end of 5-20 min of incubation, the heart did not take up the radioactivity while the spleen did. The Km and Vmax values of uptake in the spleen were 1 x 10(-4) M and 20 nmole/g per min, respectively, and the uptake was reduced to 16.0-35.1% in the cold (4 C) and to 40.3-64.0% in Na+-free medium. Thus, the uptake was an energy-dependent active process but was only partially Na+-dependent. Spleen slices incubated with 14C-DMPEA-free medium for 15 min following incubation with 14C-DMPEA retained 41.0-74.8% of radioactivity. The uptake was insensitive to norepinephrine (0.313 and 0.939 muM), dopamine (9.98 muM), 5-hydroxytryptamine (5 muM), cocaine (14.8 muM), 1-amphetamine (0.3 and 300 muM), d-amphetamine (300 muM), and normetanephrine (45.7 muM). 6-Hydroxydopamine treatment of rats, which produced 93% reduction in the splenic norepinephrine content, did not significantly reduce uptake. Thus, the uptake of DMPEA into the spleen is not by adrenergic neurones.", "contents": "Uptake of 3,4-dimethoxyphenylethylamine-1-14C (14C-DMPEA) by rat tissues in vitro. Rat heart and spleen slices were incubated with 3,4-dimethoxyphenylethylamine-1-14C(14C-DMPEA) in Krebs medium at 37 C. At the end of 5-20 min of incubation, the heart did not take up the radioactivity while the spleen did. The Km and Vmax values of uptake in the spleen were 1 x 10(-4) M and 20 nmole/g per min, respectively, and the uptake was reduced to 16.0-35.1% in the cold (4 C) and to 40.3-64.0% in Na+-free medium. Thus, the uptake was an energy-dependent active process but was only partially Na+-dependent. Spleen slices incubated with 14C-DMPEA-free medium for 15 min following incubation with 14C-DMPEA retained 41.0-74.8% of radioactivity. The uptake was insensitive to norepinephrine (0.313 and 0.939 muM), dopamine (9.98 muM), 5-hydroxytryptamine (5 muM), cocaine (14.8 muM), 1-amphetamine (0.3 and 300 muM), d-amphetamine (300 muM), and normetanephrine (45.7 muM). 6-Hydroxydopamine treatment of rats, which produced 93% reduction in the splenic norepinephrine content, did not significantly reduce uptake. Thus, the uptake of DMPEA into the spleen is not by adrenergic neurones."} {"id": "PMID:1260078", "title": "Concentration of 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan in the cerebrospinal fluid of depressed patients before and after ECT.", "content": "Cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5HIAA), tryptophan (TRYP), and homovanillic acid (HVA), were determined prior to electroconvulsive therapy (ECT) and after an average course of 6.7 ECT in six endogenous depressed patients. Depression rating scale (DRS) scores were also obtained by a \"blind\" research psychiatrist before and after ECT at the time of each lumbar puncture. ECT markedly reduced DRS scores but did not significantly alter CSF levels of 5HIAA, TRYP, or HVA. We found no correlation between ECT-induced DRS score reductions and changes in any of the CSF constituents studied, or between the absolute DRS score and the corresponding CSF concentration of any of the compounds. These data are consistent with those previously reported for ECT and do not suggest that ECT alters cerebral amine metabolism in depressed patients. Neither do they provide any evidence for direct amine mediation of the depression-relieving effects of ECT in man, nor for any relation between severity of depressive illness and CSF concentrations of 5HIAA, TRYP, or HVA.", "contents": "Concentration of 5-hydroxyindoleacetic acid, homovanillic acid, and tryptophan in the cerebrospinal fluid of depressed patients before and after ECT. Cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5HIAA), tryptophan (TRYP), and homovanillic acid (HVA), were determined prior to electroconvulsive therapy (ECT) and after an average course of 6.7 ECT in six endogenous depressed patients. Depression rating scale (DRS) scores were also obtained by a \"blind\" research psychiatrist before and after ECT at the time of each lumbar puncture. ECT markedly reduced DRS scores but did not significantly alter CSF levels of 5HIAA, TRYP, or HVA. We found no correlation between ECT-induced DRS score reductions and changes in any of the CSF constituents studied, or between the absolute DRS score and the corresponding CSF concentration of any of the compounds. These data are consistent with those previously reported for ECT and do not suggest that ECT alters cerebral amine metabolism in depressed patients. Neither do they provide any evidence for direct amine mediation of the depression-relieving effects of ECT in man, nor for any relation between severity of depressive illness and CSF concentrations of 5HIAA, TRYP, or HVA."} {"id": "PMID:1260079", "title": "Comparison of the effects of maprotiline (ludiomil) and clomipramine (anafranil) on serotonin uptake and tryptophan-binding in plasma.", "content": "The influence of maprotiline or clomipramine on plasma tryptophan-binding and brain tryptophan was studied in rats. Neither compound altered tryptophan-binding nor brain tryptophan levels after acute of chronic treatment. In a comparative study maprotiline and clomipramine were administered to healthy volunteers for 4 days and the concentrations of total and free tryptophan in plasma were determined. Serotonin uptake was also measured in the platelets from these subjects. Maprotiline treatment did not inhibit serotonin uptake nor did it have any influence on plasma tryptophan binding. Clomipramine also had no influence on plasma tryptophan-binding but strongly inhibited serotonin uptake into platelets. These results confirm the earlier observation that maprotiline has no influence on serotonin uptake and can be clearly distinguished from clomipramine.", "contents": "Comparison of the effects of maprotiline (ludiomil) and clomipramine (anafranil) on serotonin uptake and tryptophan-binding in plasma. The influence of maprotiline or clomipramine on plasma tryptophan-binding and brain tryptophan was studied in rats. Neither compound altered tryptophan-binding nor brain tryptophan levels after acute of chronic treatment. In a comparative study maprotiline and clomipramine were administered to healthy volunteers for 4 days and the concentrations of total and free tryptophan in plasma were determined. Serotonin uptake was also measured in the platelets from these subjects. Maprotiline treatment did not inhibit serotonin uptake nor did it have any influence on plasma tryptophan binding. Clomipramine also had no influence on plasma tryptophan-binding but strongly inhibited serotonin uptake into platelets. These results confirm the earlier observation that maprotiline has no influence on serotonin uptake and can be clearly distinguished from clomipramine."} {"id": "PMID:1260094", "title": "Prediction of the secondary and tertiary structure of plastocyanin.", "content": "The amino acid sequences of nine plastocyanins were examined using four published methods for the prediction of secondary structure in proteins. The results of the four methods were combined in such a way as to maximize agreement, and the position of alpha helices, beta sheets, and beta turns in plastocyanin was predicted. From this result and other information, such as the position of conserved residues and the requirements for coordination of copper, a preliminary model for the mainchain folding of the molecule was presented.", "contents": "Prediction of the secondary and tertiary structure of plastocyanin. The amino acid sequences of nine plastocyanins were examined using four published methods for the prediction of secondary structure in proteins. The results of the four methods were combined in such a way as to maximize agreement, and the position of alpha helices, beta sheets, and beta turns in plastocyanin was predicted. From this result and other information, such as the position of conserved residues and the requirements for coordination of copper, a preliminary model for the mainchain folding of the molecule was presented."} {"id": "PMID:1260095", "title": "Osmometric studies on self-association of pyrimidines in aqueous solutions: evidence for involvement of hydrophobic interactions.", "content": "Vapour pressure osmometric studies were performed on stacking self-association of 25 uracil derivatives variously C- and N-substituted with polar and alkyl groups in aqueous solution at various temperatures. The respective equilibrium association constants Kst were computed on the assumption of the isodesmic model of self-association (K2=K3=...=Kn=Kst). Enthalpies of association for most of the compounds studied were obtained from the temperature-dependence of Kst, according to the van 't Hoff equation. Analysis of the equilibrium and thermodynamic parameters in terms of the association mechanism demonstrated the involvement of classical hydrophobic interactiors in the stabilization of complexes of di-and higher alkylated uracils. Data for the derivatives substituted with polar groups proved consistent with the predominant involvement of dipole-induced dipole forces in the association.", "contents": "Osmometric studies on self-association of pyrimidines in aqueous solutions: evidence for involvement of hydrophobic interactions. Vapour pressure osmometric studies were performed on stacking self-association of 25 uracil derivatives variously C- and N-substituted with polar and alkyl groups in aqueous solution at various temperatures. The respective equilibrium association constants Kst were computed on the assumption of the isodesmic model of self-association (K2=K3=...=Kn=Kst). Enthalpies of association for most of the compounds studied were obtained from the temperature-dependence of Kst, according to the van 't Hoff equation. Analysis of the equilibrium and thermodynamic parameters in terms of the association mechanism demonstrated the involvement of classical hydrophobic interactiors in the stabilization of complexes of di-and higher alkylated uracils. Data for the derivatives substituted with polar groups proved consistent with the predominant involvement of dipole-induced dipole forces in the association."} {"id": "PMID:1260097", "title": "Kinetic cooperativity in the concerted model for allosteric enzymes.", "content": "The cooperativity of enzyme-substrate interactions is investigated in the concerted allosteric model of Monod, Wyman and Changeux. The general case of K-V systems is considered, in which the two protomer conformational states R and T postulated in the theory differ in catalytic and binding properties. An expression for the Hill coefficient nH defined with respect to the asymptotic velocity V infinity to is analyzed in conditions which exclude substrate inhibition. Kinetic cooperativity is always positive (nH greater than 1) in the case of a dimer enzyme, and in the case of an inactive T state. Slight kinetic negative cooperativity (nH less than 1) occurs under restrictive conditions for larger numbers of protomers when the substrate binds significantly to the less active state of the enzyme, but the phenomenon remains negligible for trimers and tetramers. These conclusions differ from those obtained [A. Goldbeter, J. Mol.Biol.90 (1974) 185] with the Hill coefficient based on the absolute maximum velocity, which may exceed the experimental value V infinity to in K-V systems. The results extend those of Paulus and DeRiel [J. Mol. Biol. 97 (1975) 667] and support the view that in most cases, negative cooperativity is not compatible with a mechanism based on a concerted and conservative allosteric transition. The Hill coefficients for binding and catalysis are compared in K-V systems.", "contents": "Kinetic cooperativity in the concerted model for allosteric enzymes. The cooperativity of enzyme-substrate interactions is investigated in the concerted allosteric model of Monod, Wyman and Changeux. The general case of K-V systems is considered, in which the two protomer conformational states R and T postulated in the theory differ in catalytic and binding properties. An expression for the Hill coefficient nH defined with respect to the asymptotic velocity V infinity to is analyzed in conditions which exclude substrate inhibition. Kinetic cooperativity is always positive (nH greater than 1) in the case of a dimer enzyme, and in the case of an inactive T state. Slight kinetic negative cooperativity (nH less than 1) occurs under restrictive conditions for larger numbers of protomers when the substrate binds significantly to the less active state of the enzyme, but the phenomenon remains negligible for trimers and tetramers. These conclusions differ from those obtained [A. Goldbeter, J. Mol.Biol.90 (1974) 185] with the Hill coefficient based on the absolute maximum velocity, which may exceed the experimental value V infinity to in K-V systems. The results extend those of Paulus and DeRiel [J. Mol. Biol. 97 (1975) 667] and support the view that in most cases, negative cooperativity is not compatible with a mechanism based on a concerted and conservative allosteric transition. The Hill coefficients for binding and catalysis are compared in K-V systems."} {"id": "PMID:1260098", "title": "Equilibrium gel permeation: a single-photon counting spectrophotometer for studies of protein interaction.", "content": "When a small column or flow cell packed with gel particles is completely saturated with a solution containing molecular species of interest, the average cross-sectional area occupied by the solute (partition cross section) is conveniently and precisely determined by direct optical scanning. For a mixture of interacting solutes this equilibrium gel permeation measurement yields the weight average of the species partition cross sections and the variation of this quantity with solute concentration permits determination of the solute interaction parameters (stoichiometry, equilibrium constants). We have developed a computer-controlled single-photon counting spectrophotometer for these measurements. The instrument exhibits high precision over a wide range of optical density. With counting times in the range of 10-1000 s the standard deviations on optical densities of protein solutions measured at 220 nm are typically 0.0006 at 1 OD, 0.002 at 2 OD, 0.005 at 4 OD. Beer's law tests show that deviations from linearity are less than these precision limits. Partition cross-section measurements for proteins can be made with an accuracy of better than 0.001 and information can be obtained with protein solutions at least as low as 1 mug/ml.", "contents": "Equilibrium gel permeation: a single-photon counting spectrophotometer for studies of protein interaction. When a small column or flow cell packed with gel particles is completely saturated with a solution containing molecular species of interest, the average cross-sectional area occupied by the solute (partition cross section) is conveniently and precisely determined by direct optical scanning. For a mixture of interacting solutes this equilibrium gel permeation measurement yields the weight average of the species partition cross sections and the variation of this quantity with solute concentration permits determination of the solute interaction parameters (stoichiometry, equilibrium constants). We have developed a computer-controlled single-photon counting spectrophotometer for these measurements. The instrument exhibits high precision over a wide range of optical density. With counting times in the range of 10-1000 s the standard deviations on optical densities of protein solutions measured at 220 nm are typically 0.0006 at 1 OD, 0.002 at 2 OD, 0.005 at 4 OD. Beer's law tests show that deviations from linearity are less than these precision limits. Partition cross-section measurements for proteins can be made with an accuracy of better than 0.001 and information can be obtained with protein solutions at least as low as 1 mug/ml."} {"id": "PMID:1260099", "title": "High-sensitivity linear dichroism as a tool for equilibrium analysis in biochemistry. Stability constant of DNA--ethidiumbromide complex.", "content": "A stoichiometrical application of a sensitive method for linear dichroism (LD) detection is suggested for biochemical purposes. The complex formation between a binding site on a polynucleotide and a ligand may be studied with high precision if the following conditions are fulfilled: (1) The polymer can be given a fixed degree of orientation. (2) The site has a specific orientation with respect to the orientation axis of the polymer (e.g., intercalation). (3) The ligand has an anisotropic optical absorption property. The method was applied to studying the complex between DNA and ethidiumbromide, which was detected by LD with precision of +/- 0.5 X 10(-7) M in a 4 X 10(-4) M DNA solution, i.e., 0.1% occupation of the total site concentration can be detected. The complexation could be explained by a single type of site (n = 0.14 +/- 0.01 sites per nucleotide residue) and a stability constant K1 = (2.5 +/- 1) X 10(5) M-1 at 0.2 M ionic strength. From the specific LD an average angle 60 degrees was concluded between the helix axis and the long axis of the ethidiumbromide molecule. This value formally contradicts the Watson-Crick model or the intercalation model but may be explained by extension and deformation effects on the xhain by the flow.", "contents": "High-sensitivity linear dichroism as a tool for equilibrium analysis in biochemistry. Stability constant of DNA--ethidiumbromide complex. A stoichiometrical application of a sensitive method for linear dichroism (LD) detection is suggested for biochemical purposes. The complex formation between a binding site on a polynucleotide and a ligand may be studied with high precision if the following conditions are fulfilled: (1) The polymer can be given a fixed degree of orientation. (2) The site has a specific orientation with respect to the orientation axis of the polymer (e.g., intercalation). (3) The ligand has an anisotropic optical absorption property. The method was applied to studying the complex between DNA and ethidiumbromide, which was detected by LD with precision of +/- 0.5 X 10(-7) M in a 4 X 10(-4) M DNA solution, i.e., 0.1% occupation of the total site concentration can be detected. The complexation could be explained by a single type of site (n = 0.14 +/- 0.01 sites per nucleotide residue) and a stability constant K1 = (2.5 +/- 1) X 10(5) M-1 at 0.2 M ionic strength. From the specific LD an average angle 60 degrees was concluded between the helix axis and the long axis of the ethidiumbromide molecule. This value formally contradicts the Watson-Crick model or the intercalation model but may be explained by extension and deformation effects on the xhain by the flow."} {"id": "PMID:1260100", "title": "A study of rhodopsin-detergent micelles by transient electric birefringence.", "content": "The hydrodynamic method of transient electric birefringence has been used to study bovine rhodopsin solubilized in two detergents, 0.02% Ammonyx LO and 0.045% digitonin. All measurements are interpreted as the sum of two exponentials by which the relaxation times yield the rotary diffusion coefficients for ellipsoids of revolution. The semi-major and minor axes for prolate ellipsoid models have been calculated and their axial ratio, 6.8, in both detergents, is in line with recent reports on the structure of rhodopsin. Studies on bleached rhodopsin showed a large increase in axial ratio in 0.02% Ammonyx LO.", "contents": "A study of rhodopsin-detergent micelles by transient electric birefringence. The hydrodynamic method of transient electric birefringence has been used to study bovine rhodopsin solubilized in two detergents, 0.02% Ammonyx LO and 0.045% digitonin. All measurements are interpreted as the sum of two exponentials by which the relaxation times yield the rotary diffusion coefficients for ellipsoids of revolution. The semi-major and minor axes for prolate ellipsoid models have been calculated and their axial ratio, 6.8, in both detergents, is in line with recent reports on the structure of rhodopsin. Studies on bleached rhodopsin showed a large increase in axial ratio in 0.02% Ammonyx LO."} {"id": "PMID:1260101", "title": "A comparative study on bovine alpha-lactalbumin and lysozyme by nanosecond fluorometry.", "content": "Analysis of the time decay of fluorescence anisotropy of 1-dimethylaminoaphthalene-5-sulfonyl (DNS) and fluorescamine derivatives of bovine alpha-lactalbumin and lysozyme reveals that no significant differences in mean rotational relaxation times are present. While fluorescamine molecules appear to orient randomly on these proteins, DNS is bound with a preferential orientation. Other fluorescence characteristics of the labels are also cited.", "contents": "A comparative study on bovine alpha-lactalbumin and lysozyme by nanosecond fluorometry. Analysis of the time decay of fluorescence anisotropy of 1-dimethylaminoaphthalene-5-sulfonyl (DNS) and fluorescamine derivatives of bovine alpha-lactalbumin and lysozyme reveals that no significant differences in mean rotational relaxation times are present. While fluorescamine molecules appear to orient randomly on these proteins, DNS is bound with a preferential orientation. Other fluorescence characteristics of the labels are also cited."} {"id": "PMID:1260111", "title": "A new technique for the detection of metabolites labelled by the isotope 13C using mass fragmentography.", "content": "The detection of a small amount of 13C labelled methyl benzoate and its metabolites in human urine dosed 13C labelled aspirin was carried out by a new mass fragmentographic technique.", "contents": "A new technique for the detection of metabolites labelled by the isotope 13C using mass fragmentography. The detection of a small amount of 13C labelled methyl benzoate and its metabolites in human urine dosed 13C labelled aspirin was carried out by a new mass fragmentographic technique."} {"id": "PMID:1260112", "title": "Biological implications of the reaction possibilities of the proximate carcinogenic compound, N-hydroxy-2-fluorenylacetamide.", "content": "The biological implications, the reaction possibilities and the structure of different derivatives of N-hydroxy-2-fluorenylacetamide have been described.", "contents": "Biological implications of the reaction possibilities of the proximate carcinogenic compound, N-hydroxy-2-fluorenylacetamide. The biological implications, the reaction possibilities and the structure of different derivatives of N-hydroxy-2-fluorenylacetamide have been described."} {"id": "PMID:1260113", "title": "Derivatization of aminoalkylphosphonic acids for characterization by gas chromatography mass spectrometry.", "content": "A general derivatization method has been developed for both primary and secondary aminoalkyl-phosphonic acids. Derivatization is effected by reaction with trifluoroacetic acid and trifluoroacetic acid anhydride followed by esterification using ethereal diazo-n-butane. This method can be used for microgram quantities and permits ready characterization by both gas chromatography and gas chromatography mass spectrometry. The structure of this derivative has been verified by mass spectrometry and proton magnetic resonance. Fragmentation patterns were confirmed by high resolution mass spectrometry, isotope labeling and the formation of derivative analogs.", "contents": "Derivatization of aminoalkylphosphonic acids for characterization by gas chromatography mass spectrometry. A general derivatization method has been developed for both primary and secondary aminoalkyl-phosphonic acids. Derivatization is effected by reaction with trifluoroacetic acid and trifluoroacetic acid anhydride followed by esterification using ethereal diazo-n-butane. This method can be used for microgram quantities and permits ready characterization by both gas chromatography and gas chromatography mass spectrometry. The structure of this derivative has been verified by mass spectrometry and proton magnetic resonance. Fragmentation patterns were confirmed by high resolution mass spectrometry, isotope labeling and the formation of derivative analogs."} {"id": "PMID:1260114", "title": "The mass spectrometric identification of dipeptide mixtures obtained from dipeptidylaminopeptidase. I--Hydrolysates.", "content": "The amino acid sequence of a polypeptide can be deduced by an identification of all the dipeptides obtained from a Dipeptidylaminopeptidase I hydrolysate of the original polypeptide and its des N-terminal amino acid derivative. The components of such dipeptide mixtures can be readily identified from the chemical ionization (helium) mass spectra of their N-ethoxycarbonylpropenyl methyl ester derivatives without prior separation. The pyrolytic conversion of N-protected peptide dimethyltrideuteromethyl anilinium salts to their methyl esters in the direct insertion probe of a mass spectrometer was found to be most suitable for the derivatization of such dipeptide mixtures.", "contents": "The mass spectrometric identification of dipeptide mixtures obtained from dipeptidylaminopeptidase. I--Hydrolysates. The amino acid sequence of a polypeptide can be deduced by an identification of all the dipeptides obtained from a Dipeptidylaminopeptidase I hydrolysate of the original polypeptide and its des N-terminal amino acid derivative. The components of such dipeptide mixtures can be readily identified from the chemical ionization (helium) mass spectra of their N-ethoxycarbonylpropenyl methyl ester derivatives without prior separation. The pyrolytic conversion of N-protected peptide dimethyltrideuteromethyl anilinium salts to their methyl esters in the direct insertion probe of a mass spectrometer was found to be most suitable for the derivatization of such dipeptide mixtures."} {"id": "PMID:1260115", "title": "Mass spectral studies on prostaglandins. II--Prostaglandins E1 and E2.", "content": "The mass spectroscopic behaviour of the methyl ester of prostaglandins E1 and E2 has been studied with the aid of low eV spectra, measurements on metastable ion decompositions and high resolution mass measurements. Mechanisms are proposed for the formation of the majority of the abundant fragment ions of these biologically important compounds. The mass spectra of free acids are also discussed.", "contents": "Mass spectral studies on prostaglandins. II--Prostaglandins E1 and E2. The mass spectroscopic behaviour of the methyl ester of prostaglandins E1 and E2 has been studied with the aid of low eV spectra, measurements on metastable ion decompositions and high resolution mass measurements. Mechanisms are proposed for the formation of the majority of the abundant fragment ions of these biologically important compounds. The mass spectra of free acids are also discussed."} {"id": "PMID:1260116", "title": "The measurement of diphenoxylic acid in plasma following administration of diphenoxylate.", "content": "The measurement of diphenoxylic acid, the major metabolite of diphenoxylate, has been performed in man using a deuterium labelled internal standard and multiple ion monitoring using a gas chromatograph mass spectrometer. The determination of plasma concentrations following administration of diphenoxylate to man is described.", "contents": "The measurement of diphenoxylic acid in plasma following administration of diphenoxylate. The measurement of diphenoxylic acid, the major metabolite of diphenoxylate, has been performed in man using a deuterium labelled internal standard and multiple ion monitoring using a gas chromatograph mass spectrometer. The determination of plasma concentrations following administration of diphenoxylate to man is described."} {"id": "PMID:1260117", "title": "A device for monitoring selected peaks in repetitively scanned mass spectra.", "content": "A selective ion monitor for the Perkin-Elmer Model 270 gas chromatograph mass spectrometer is described.", "contents": "A device for monitoring selected peaks in repetitively scanned mass spectra. A selective ion monitor for the Perkin-Elmer Model 270 gas chromatograph mass spectrometer is described."} {"id": "PMID:1260118", "title": "Granulocyte function in experimental human endotoxemia.", "content": "The effects of endotoxin administration on in vitro granulocyte function were studied in normal man. Four healthy volunteers received an intravenous injection of Pseudomonas endotoxin, 0.1 mug/kg. Endotoxemia resulted in transient neutropenia followed by a rebound neutrophilia. The nadir of the granulocyte count occurred at about 1 hr and maximal neutrophilia 2-4 hr after endotoxin administration. Throughout this time period, neutrophil phagocytosis and killing of Candida albicans were normal, as were resting and postphagocytic glucose metabolism and leukocyte random migration. However, postendotoxin neutrophils demonstrated a markedly decreased chemotactic response in Boyden chambers. The defect was maximal 1 hr after endotoxin administration and persisted 3-4 hr. These observations suggest that, in addition to neutropenia, endotoxin can transiently cause a chemotactic defect or select for a population of circulating neutrophils with an impairment of chemotactic activity.", "contents": "Granulocyte function in experimental human endotoxemia. The effects of endotoxin administration on in vitro granulocyte function were studied in normal man. Four healthy volunteers received an intravenous injection of Pseudomonas endotoxin, 0.1 mug/kg. Endotoxemia resulted in transient neutropenia followed by a rebound neutrophilia. The nadir of the granulocyte count occurred at about 1 hr and maximal neutrophilia 2-4 hr after endotoxin administration. Throughout this time period, neutrophil phagocytosis and killing of Candida albicans were normal, as were resting and postphagocytic glucose metabolism and leukocyte random migration. However, postendotoxin neutrophils demonstrated a markedly decreased chemotactic response in Boyden chambers. The defect was maximal 1 hr after endotoxin administration and persisted 3-4 hr. These observations suggest that, in addition to neutropenia, endotoxin can transiently cause a chemotactic defect or select for a population of circulating neutrophils with an impairment of chemotactic activity."} {"id": "PMID:1260119", "title": "Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes.", "content": "The addition of 0.1 mug/ml of phorbol myristate acetate (PMA) to a suspension of resting human neutrophils causes a marked stimulation of all aspects of cellular oxidative metabolism normally associated with phagocytosis. PMA induces a greatly increased rate of glucose oxidation via the hexose monophosphate shunt, increased production of superoxide anion and of hydrogen peroxide, increased cellular chemiluminescence, and increased iodination of protein material. The time course of hexose monophosphate shunt activation and of chemiluminescence are similar to those observed following phagocytosis of opsonized zymosan; the levels of activation achieved in all cases approximate those seen following phagocytosis. These phenomena are not simply reflections of altered cellular permeability, since PMA actually inhibits the uptake of radioactive 2-deoxyglucose and of uniformly labeled amino acids. The addition of PMA similarly inhibits the uptake of 14C-labeled bacteria, suggesting a competition between the effect of the chemical and the process of phagocytosis. These results suggest that PMA activates the cell in the same manner as does phagocytosis. This compound should provide a useful tool for elucidating the metabolic events underlying the phenomena of phagocytosis and bacterial killing by polymorphonuclear leukocytes.", "contents": "Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes. The addition of 0.1 mug/ml of phorbol myristate acetate (PMA) to a suspension of resting human neutrophils causes a marked stimulation of all aspects of cellular oxidative metabolism normally associated with phagocytosis. PMA induces a greatly increased rate of glucose oxidation via the hexose monophosphate shunt, increased production of superoxide anion and of hydrogen peroxide, increased cellular chemiluminescence, and increased iodination of protein material. The time course of hexose monophosphate shunt activation and of chemiluminescence are similar to those observed following phagocytosis of opsonized zymosan; the levels of activation achieved in all cases approximate those seen following phagocytosis. These phenomena are not simply reflections of altered cellular permeability, since PMA actually inhibits the uptake of radioactive 2-deoxyglucose and of uniformly labeled amino acids. The addition of PMA similarly inhibits the uptake of 14C-labeled bacteria, suggesting a competition between the effect of the chemical and the process of phagocytosis. These results suggest that PMA activates the cell in the same manner as does phagocytosis. This compound should provide a useful tool for elucidating the metabolic events underlying the phenomena of phagocytosis and bacterial killing by polymorphonuclear leukocytes."} {"id": "PMID:1260120", "title": "The anemia of chronic renal failure and chronic diseases: in vitro studies of erythropoiesis.", "content": "The presence of a serum factor in chronic renal failure (CRF) which inhibits erythropoietin-stimulated erythropoiesis was studied, using a technique in which dog marrow cells were stimulated to produce heme in the presence of human serum. In the total series comparing 27 normal sera with 52 CRF sera, less heme was synthesized when the system contained CRF sera (total series, p = 0.0001). There was no evidence of inhibition of heme synthesis by serum from 12 patients with the anemia of chronic diseases (CD). Mixing experiments with normal and CRF sera suggested that this defect in CRF serum was not due to lack of a factor necessary for heme synthesis. Addition of urea, creatinine, and guanidinosuccinic acid to normal serum did not impair its ability to support erythropoiesis in this system. These data demonstrated that serum from patients with CRF contains a material inhibiting erythropoiesis in vitro, We propose that the material is responsible, in part, for the clinically severe anemia seen in these patients.", "contents": "The anemia of chronic renal failure and chronic diseases: in vitro studies of erythropoiesis. The presence of a serum factor in chronic renal failure (CRF) which inhibits erythropoietin-stimulated erythropoiesis was studied, using a technique in which dog marrow cells were stimulated to produce heme in the presence of human serum. In the total series comparing 27 normal sera with 52 CRF sera, less heme was synthesized when the system contained CRF sera (total series, p = 0.0001). There was no evidence of inhibition of heme synthesis by serum from 12 patients with the anemia of chronic diseases (CD). Mixing experiments with normal and CRF sera suggested that this defect in CRF serum was not due to lack of a factor necessary for heme synthesis. Addition of urea, creatinine, and guanidinosuccinic acid to normal serum did not impair its ability to support erythropoiesis in this system. These data demonstrated that serum from patients with CRF contains a material inhibiting erythropoiesis in vitro, We propose that the material is responsible, in part, for the clinically severe anemia seen in these patients."} {"id": "PMID:1260121", "title": "Sterospecific tissue uptake and nuclear accumulation of testosterone in the development of the mouse erythropoietic spleen.", "content": "A double isotope ratio technique was used to estimate the specific binding of testosterone (T), as opposed to its biologically nonactive stereoisomer, epitestosterone (Epi T). The mouse erythropoietic spleen formed in response to a phenylhydrazine-induced hemolytic anemia was used as the target organ. Spleen minces from preanemic mice, as well as those in the early and late phases of erythropoietic spleen development, were incubated with 10(-9) M of 14C-T and 3H-EpiT, and the selective uptake of T was calculated from the 14C/3H ratio measured in the media before and after incubation, as well as in the subcellular fractions of the minces. Preferential uptake of T was seen in the early phase of development, but not in spleens obtained from preanemic animals or those in the late phase. There was no evidence of metabolic conversion of T or EpiT. The selective uptake of T by early phase spleens was reflected in a preferential nuclear accumulation of T. These data represent the first demonstration of a specific binding of T in vitro to a developing erythroid tissue.", "contents": "Sterospecific tissue uptake and nuclear accumulation of testosterone in the development of the mouse erythropoietic spleen. A double isotope ratio technique was used to estimate the specific binding of testosterone (T), as opposed to its biologically nonactive stereoisomer, epitestosterone (Epi T). The mouse erythropoietic spleen formed in response to a phenylhydrazine-induced hemolytic anemia was used as the target organ. Spleen minces from preanemic mice, as well as those in the early and late phases of erythropoietic spleen development, were incubated with 10(-9) M of 14C-T and 3H-EpiT, and the selective uptake of T was calculated from the 14C/3H ratio measured in the media before and after incubation, as well as in the subcellular fractions of the minces. Preferential uptake of T was seen in the early phase of development, but not in spleens obtained from preanemic animals or those in the late phase. There was no evidence of metabolic conversion of T or EpiT. The selective uptake of T by early phase spleens was reflected in a preferential nuclear accumulation of T. These data represent the first demonstration of a specific binding of T in vitro to a developing erythroid tissue."} {"id": "PMID:1260122", "title": "Effect of erythropoietin on chromosomal protein synthesis.", "content": "The spleen of the exhypoxic polycythemic mouse was employed to study the effect of erythropoietin on the synthesis of chromosomal proteins. At 1, 3, 18, 36, 45, and 72 hr after injection of erythropoietin, spleens were removed, minced, and incubated with 3H-arginine for 1 hr. Chromatin was isolated from the labeled splenic tissue and separated into histone and nonhistone protein (NHP) fractions. An increase in the incorporation of 3H-arginine into NHP occurred within 3 hr and into histones by 18 hr. Incorporation of 3H-arginine into both histones and NHP was maximal by 45 hr and had declined by 72 hr. Total histone specific activity increased fivefold while NHP specific activity increased twofold. Histones and NHP were fractionated on polyacrylamide gels and a double isotope labeling proceudre was used to study the synthesis of the individual histone proteins and NHP. Following administration of erythropoietin, there was a coordinate increase in the specific activity of all five major histone proteins and most of the NHP. The earliest change in specific activity of both histones and NHP occurred prior to the appearance of morphologically identifiable erythroblasts in the spleen.", "contents": "Effect of erythropoietin on chromosomal protein synthesis. The spleen of the exhypoxic polycythemic mouse was employed to study the effect of erythropoietin on the synthesis of chromosomal proteins. At 1, 3, 18, 36, 45, and 72 hr after injection of erythropoietin, spleens were removed, minced, and incubated with 3H-arginine for 1 hr. Chromatin was isolated from the labeled splenic tissue and separated into histone and nonhistone protein (NHP) fractions. An increase in the incorporation of 3H-arginine into NHP occurred within 3 hr and into histones by 18 hr. Incorporation of 3H-arginine into both histones and NHP was maximal by 45 hr and had declined by 72 hr. Total histone specific activity increased fivefold while NHP specific activity increased twofold. Histones and NHP were fractionated on polyacrylamide gels and a double isotope labeling proceudre was used to study the synthesis of the individual histone proteins and NHP. Following administration of erythropoietin, there was a coordinate increase in the specific activity of all five major histone proteins and most of the NHP. The earliest change in specific activity of both histones and NHP occurred prior to the appearance of morphologically identifiable erythroblasts in the spleen."} {"id": "PMID:1260123", "title": "Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. II. Distribution and cellularity of the marrow in irradiated and transfused animals.", "content": "Dogs were given transfusions of cryopreserved autologous mononuclear blood leukocytes after 1200 roentgens (R) (midline dose) whole-body x-irradiation. Bone marrow repopulation was studied by means of histomorphological methods at days 9 and 10 after transfusion of an average of 3 X 10(9), 7 X 10(9), 13 X 10(9), and 31 X 10(9) cells. The return of marrow cellularity to normal values was related to the number of cells transfused. With low cell doses (3 X 10(9) and 7 X 10(9)), the marrow regeneration at 10 days was focal. There were groups of cells (colonies) showing either erythropoiesis, myelopoiesis, or megakaryocytopoiesis in the osteal niches of the trabecular bones. Frequently such niches were seen showing complete cellular recovery next to niches with complete aplasia. With higher cell doses, all niches showed hemopoietic regeneration, and the cellularity approached normal values. No hemopoietic regeneration was observed in those skeletal parts that do not show hemopoiesis, even under normal circumstances.", "contents": "Regeneration of blood-forming organs after autologous leukocyte transfusion in lethally irradiated dogs. II. Distribution and cellularity of the marrow in irradiated and transfused animals. Dogs were given transfusions of cryopreserved autologous mononuclear blood leukocytes after 1200 roentgens (R) (midline dose) whole-body x-irradiation. Bone marrow repopulation was studied by means of histomorphological methods at days 9 and 10 after transfusion of an average of 3 X 10(9), 7 X 10(9), 13 X 10(9), and 31 X 10(9) cells. The return of marrow cellularity to normal values was related to the number of cells transfused. With low cell doses (3 X 10(9) and 7 X 10(9)), the marrow regeneration at 10 days was focal. There were groups of cells (colonies) showing either erythropoiesis, myelopoiesis, or megakaryocytopoiesis in the osteal niches of the trabecular bones. Frequently such niches were seen showing complete cellular recovery next to niches with complete aplasia. With higher cell doses, all niches showed hemopoietic regeneration, and the cellularity approached normal values. No hemopoietic regeneration was observed in those skeletal parts that do not show hemopoiesis, even under normal circumstances."} {"id": "PMID:1260124", "title": "Acquired XO/XY clones in bone marrow of a patient with paroxysmal nocturnal hemoglobinuria (PNH).", "content": "Cytogenetic studies showed both 45XO and 46XY clones in the bone marrow of a 76-yr-old male with a 17-yr history of paroxysmal nocturnal hemoglobinuria (PNH). 55Fe incorporation studies demonstrated that both clones involved the hematopoietic stem cells. The loss of the Y chromosome may reflect an aging phenomenon, rather than be related to the PNH.", "contents": "Acquired XO/XY clones in bone marrow of a patient with paroxysmal nocturnal hemoglobinuria (PNH). Cytogenetic studies showed both 45XO and 46XY clones in the bone marrow of a 76-yr-old male with a 17-yr history of paroxysmal nocturnal hemoglobinuria (PNH). 55Fe incorporation studies demonstrated that both clones involved the hematopoietic stem cells. The loss of the Y chromosome may reflect an aging phenomenon, rather than be related to the PNH."} {"id": "PMID:1260126", "title": "Mechanism of dilutional anemia in massive splenomegaly.", "content": "Twenty patients with anemia and massive splenomegaly were studied in order to elucidate the mechanism by which splenomegaly results in plasma volume expansion. In 18 patients, increased plasma volume accounted for most of the anemia. Fourteen patients had an exaggerated renin response to standing, mean 1967 +/- 613 (SE) ng angiotensin ll/100 ml plasma (p less than 0.05). The mean resting forearm blood flow was increased 3.47 +/- 0.32 (SE) ml/100 ml forearm tissue (p less than 0.001). The venous capacitance was normal, as contrasted to a marked decrease in venous capacitance in patients with anemia of comparable degree without splenomegaly. Cardiac indices were increased in 10 of 11 patients (range 4.1-8.1 liters/min/sq m). In nine of ten patients oxygen consumption was increased (range 147-231 ml/min/sq m). Splenectomy was performed on 14 patients. Splenic blood flow was elevated in four of four patients (range 750-2000 ml/min). Splenic A-V oxygen difference was exaggerated in seven of seven patients and in three of three patients splenic indocyanine-green dye dilution curve failed to show an early peak suggestive of A-V shunting in the spleen. Free portal pressure was elevated in 12 of 12 patients and decreased immediately after splenectomy. The intravascular albumin mass decreased in ten patients, was unchanged in three at 2-4 mo after splenectomy, and was accompanied by a rise in the plasma albumin concentration in nine. These data suggest that a flow-induced portal hypertension with expansion of the portal vascular space is an important early hemodynamic change. This finding, together with a decreased peripheral resistance, probably results in a decrease in effective intravascular volume, resulting in stimulation of the renin-angiotensin-aldosterone system and other renal hemodynamic changes necessary for salt and water retention. Splenectomy usually accomplishes a complete reversal of these abnormalities and correction of the anemia.", "contents": "Mechanism of dilutional anemia in massive splenomegaly. Twenty patients with anemia and massive splenomegaly were studied in order to elucidate the mechanism by which splenomegaly results in plasma volume expansion. In 18 patients, increased plasma volume accounted for most of the anemia. Fourteen patients had an exaggerated renin response to standing, mean 1967 +/- 613 (SE) ng angiotensin ll/100 ml plasma (p less than 0.05). The mean resting forearm blood flow was increased 3.47 +/- 0.32 (SE) ml/100 ml forearm tissue (p less than 0.001). The venous capacitance was normal, as contrasted to a marked decrease in venous capacitance in patients with anemia of comparable degree without splenomegaly. Cardiac indices were increased in 10 of 11 patients (range 4.1-8.1 liters/min/sq m). In nine of ten patients oxygen consumption was increased (range 147-231 ml/min/sq m). Splenectomy was performed on 14 patients. Splenic blood flow was elevated in four of four patients (range 750-2000 ml/min). Splenic A-V oxygen difference was exaggerated in seven of seven patients and in three of three patients splenic indocyanine-green dye dilution curve failed to show an early peak suggestive of A-V shunting in the spleen. Free portal pressure was elevated in 12 of 12 patients and decreased immediately after splenectomy. The intravascular albumin mass decreased in ten patients, was unchanged in three at 2-4 mo after splenectomy, and was accompanied by a rise in the plasma albumin concentration in nine. These data suggest that a flow-induced portal hypertension with expansion of the portal vascular space is an important early hemodynamic change. This finding, together with a decreased peripheral resistance, probably results in a decrease in effective intravascular volume, resulting in stimulation of the renin-angiotensin-aldosterone system and other renal hemodynamic changes necessary for salt and water retention. Splenectomy usually accomplishes a complete reversal of these abnormalities and correction of the anemia."} {"id": "PMID:1260127", "title": "Immunologic evidence that the properties of human antihemophilic factor (factor VIII) are attributes of a single molecular species.", "content": "Preparations of human plasma rich in antihemophilic factor (AHF, factor VIII) correct the coagulative defect of classic hemophilic plasma, form precipitates with specific heterologous antiserum, and support aggregation of platelets by ristacetin and retention of platelets by columns of glass beads. Whether these various properties can all be attributed to a single molecular species is disputed. Antiserums were prepared in rabbits to partially purified AHF and to high molecular weight (MW) and low MW fragments separated by gel filtration through columns of agarose in the presence of 0.25 M calcium chloride. Antiserums to AHF and to its high or low MW fragments all inactivated procoagulant AHF in plasma or in preparations of AHF. In contrast, antiserums to AHF and its low MW fragment inactivated procoagulant AHF in the low MW fragment, while that against the high MW fragment lacked this property. Thus, the low MW fragment appeared to have some antigenic sites not present or accessible to the antiserum against the high MW fragment. In agreement with this, the low MW fragment did not block antiserum against the high MW fragment as tested by the capacity of this antiserum to inactivate functional AHF in plasma. These immunologic studies support the view that the various properties of preparations of human AHF are attributes of a single molecular species.", "contents": "Immunologic evidence that the properties of human antihemophilic factor (factor VIII) are attributes of a single molecular species. Preparations of human plasma rich in antihemophilic factor (AHF, factor VIII) correct the coagulative defect of classic hemophilic plasma, form precipitates with specific heterologous antiserum, and support aggregation of platelets by ristacetin and retention of platelets by columns of glass beads. Whether these various properties can all be attributed to a single molecular species is disputed. Antiserums were prepared in rabbits to partially purified AHF and to high molecular weight (MW) and low MW fragments separated by gel filtration through columns of agarose in the presence of 0.25 M calcium chloride. Antiserums to AHF and to its high or low MW fragments all inactivated procoagulant AHF in plasma or in preparations of AHF. In contrast, antiserums to AHF and its low MW fragment inactivated procoagulant AHF in the low MW fragment, while that against the high MW fragment lacked this property. Thus, the low MW fragment appeared to have some antigenic sites not present or accessible to the antiserum against the high MW fragment. In agreement with this, the low MW fragment did not block antiserum against the high MW fragment as tested by the capacity of this antiserum to inactivate functional AHF in plasma. These immunologic studies support the view that the various properties of preparations of human AHF are attributes of a single molecular species."} {"id": "PMID:1260128", "title": "Activation of the coagulation system in polycythemia vera.", "content": "Thrombosis is one of the major complications of polycythemia vera. Seventeen patients with polycythemia vera in good hematologic control were evaluated for abnormalities of the coagulation system. Activation of the intrinsic coagulation cascade was suggested by low levels of factor XII, prekallikrein, and kallikrein inhibitors in 12 of 17 patients. The group also demonstrated a significant increase in soluble fibrin complexes using plasma gel filtration on 4% agarose. Fibrin degradation products were normal and antithrombin III levels were slightly elevated. It appears that patients with polycythemia vera have chronic activation of the coagulation system, probably initiated by activation of factor XII. No correlation between the degree of coagulation abnormalities and thromboembolic complications was evident in this group of patients.", "contents": "Activation of the coagulation system in polycythemia vera. Thrombosis is one of the major complications of polycythemia vera. Seventeen patients with polycythemia vera in good hematologic control were evaluated for abnormalities of the coagulation system. Activation of the intrinsic coagulation cascade was suggested by low levels of factor XII, prekallikrein, and kallikrein inhibitors in 12 of 17 patients. The group also demonstrated a significant increase in soluble fibrin complexes using plasma gel filtration on 4% agarose. Fibrin degradation products were normal and antithrombin III levels were slightly elevated. It appears that patients with polycythemia vera have chronic activation of the coagulation system, probably initiated by activation of factor XII. No correlation between the degree of coagulation abnormalities and thromboembolic complications was evident in this group of patients."} {"id": "PMID:1260129", "title": "Preferential involvement of chromosomes no. 8 and no. 21 in acute leukemia and preleukemia.", "content": "Chromosome analyses were performed by a direct method on bone marrow cells of 147 patients with acute leukemia and preleukemia; in 53 chromosomally abnormal cell lines were found. Chromosome abnormalities due to structural alterations were observed in 48% of the aneuploid patients. Using the ASG banding technique, the exact identification of the abnormal chromosomes was successfully made in 22 aneuploid patients. Even though variability between patients existed in the chromosome changes; the nonrandom occurrence of some chromosome abnormalities was revealed, involving most frequently chromosomes No. 8 and No. 21. Abnormalities of chromosome No. 22 were not encountered, contrasting sharply with the frequent involvement of this chromosome in chronic myelogenous leukemia. The significance of the preferential involvement of No. 8 and No. 21 chromosomes is discussed in relation to leukemogenesis.", "contents": "Preferential involvement of chromosomes no. 8 and no. 21 in acute leukemia and preleukemia. Chromosome analyses were performed by a direct method on bone marrow cells of 147 patients with acute leukemia and preleukemia; in 53 chromosomally abnormal cell lines were found. Chromosome abnormalities due to structural alterations were observed in 48% of the aneuploid patients. Using the ASG banding technique, the exact identification of the abnormal chromosomes was successfully made in 22 aneuploid patients. Even though variability between patients existed in the chromosome changes; the nonrandom occurrence of some chromosome abnormalities was revealed, involving most frequently chromosomes No. 8 and No. 21. Abnormalities of chromosome No. 22 were not encountered, contrasting sharply with the frequent involvement of this chromosome in chronic myelogenous leukemia. The significance of the preferential involvement of No. 8 and No. 21 chromosomes is discussed in relation to leukemogenesis."} {"id": "PMID:1260130", "title": "Polyamine concentrations in bone marrow aspirates of children with leukemia and other malignancies.", "content": "High-pressure liquid chromatography analysis of polyamines in bone narrow from leukemic and nonleukemic subjects demonstrated increased concentrations of putrescine, spermidine, and spermine associated with increased cellularity. The most striking abnormality was the marked elevation of putrescine. Bone marrow polyamine analysis may be an adjunct for evaluation of leukemia patients.", "contents": "Polyamine concentrations in bone marrow aspirates of children with leukemia and other malignancies. High-pressure liquid chromatography analysis of polyamines in bone narrow from leukemic and nonleukemic subjects demonstrated increased concentrations of putrescine, spermidine, and spermine associated with increased cellularity. The most striking abnormality was the marked elevation of putrescine. Bone marrow polyamine analysis may be an adjunct for evaluation of leukemia patients."} {"id": "PMID:1260131", "title": "Chromosomal banding patterns in acute nonlymphocytic leukemia.", "content": "Bone marrow chromosomes obtained from 50 of 55 consecutive adult patients with acute nonlymphocytic leukemia were analyzed with quinacrine fluorescence. Twenty-five patients showed a normal karyotype and 25 an abnormal karyotype on the initial samples available for analysis. Among the 25 patients with abnormalities, the marrow cells contained 48 chromosomes in one case, 47 in two, 46 in ten, 45 in nine, 43 in two, and 42 chromosomes in one case. Seven of the ten patients with 46 chromosomes had abnormalities, primarily balanced translocations, that were not detected with the standard Giemsa stains. The analysis of all of the data available revealed the presence of nonrandom chromosome changes such as the addition of No. 8, the loss of No. 7, and a gain or loss of one No. 21. the most frequent structural rearrangement was the translocation between the long arm of No. 8 and No. 21, which may also be associated with the loss of a sex chromosome. Chromosomal abnormalities decreased or disappeared during remission; the same abnormality recurred in relapse. Chemotherapy did not appear to produce a stable clone of aberrant cells. Evolution of the karyotype occurred in eight patients, in five of whom an additional No. 8 was observed. This pattern of chromosomal evolution in patients with acute leukemia was very similar to that observed in patients with chronic myelogenous leukemia in the blast phase.", "contents": "Chromosomal banding patterns in acute nonlymphocytic leukemia. Bone marrow chromosomes obtained from 50 of 55 consecutive adult patients with acute nonlymphocytic leukemia were analyzed with quinacrine fluorescence. Twenty-five patients showed a normal karyotype and 25 an abnormal karyotype on the initial samples available for analysis. Among the 25 patients with abnormalities, the marrow cells contained 48 chromosomes in one case, 47 in two, 46 in ten, 45 in nine, 43 in two, and 42 chromosomes in one case. Seven of the ten patients with 46 chromosomes had abnormalities, primarily balanced translocations, that were not detected with the standard Giemsa stains. The analysis of all of the data available revealed the presence of nonrandom chromosome changes such as the addition of No. 8, the loss of No. 7, and a gain or loss of one No. 21. the most frequent structural rearrangement was the translocation between the long arm of No. 8 and No. 21, which may also be associated with the loss of a sex chromosome. Chromosomal abnormalities decreased or disappeared during remission; the same abnormality recurred in relapse. Chemotherapy did not appear to produce a stable clone of aberrant cells. Evolution of the karyotype occurred in eight patients, in five of whom an additional No. 8 was observed. This pattern of chromosomal evolution in patients with acute leukemia was very similar to that observed in patients with chronic myelogenous leukemia in the blast phase."} {"id": "PMID:1260132", "title": "Unregulated growth of murine leukemic cells and suppression of normal granulocyte growth in diffusion chamber cultures.", "content": "The patterns of proliferation of C1498 mouse acute leukemic cells have been studied using the diffusion chamber technique of cell culture. These malignant cells grow to the same maximal cell concentration irrespective of initial cell input. Leukemic cells proliferate equally well with or without the stimulus of prior host irradiation. When cells cultured for several days are diluted to the original input concentration and recultured, they rapidly proliferate back to maximal cell number. All of these findings are in sharp contrast to the behavior of granulocytes from normal mouse marrow grown in the same culture system. Co-culutre of equal numbers of normal marrow cells and leukemic cells results in virtually complete inhibition of normal marrow cells and leukemic cells results in virtually complete inhibition of normal granulocyte growth. These experiments provide a means of studying malignant growth of leukemic cells, as compared to the controlled growth and differentiation of normal granulocytes, and mechanisms by which leukemic cells suppress normal granulocyte development.", "contents": "Unregulated growth of murine leukemic cells and suppression of normal granulocyte growth in diffusion chamber cultures. The patterns of proliferation of C1498 mouse acute leukemic cells have been studied using the diffusion chamber technique of cell culture. These malignant cells grow to the same maximal cell concentration irrespective of initial cell input. Leukemic cells proliferate equally well with or without the stimulus of prior host irradiation. When cells cultured for several days are diluted to the original input concentration and recultured, they rapidly proliferate back to maximal cell number. All of these findings are in sharp contrast to the behavior of granulocytes from normal mouse marrow grown in the same culture system. Co-culutre of equal numbers of normal marrow cells and leukemic cells results in virtually complete inhibition of normal marrow cells and leukemic cells results in virtually complete inhibition of normal granulocyte growth. These experiments provide a means of studying malignant growth of leukemic cells, as compared to the controlled growth and differentiation of normal granulocytes, and mechanisms by which leukemic cells suppress normal granulocyte development."} {"id": "PMID:1260133", "title": "Isolation and in vitro differentiation of human erythroid precursor cells.", "content": "There is decreased beta-globin production in beta-thalassemic reticulocytes and nucleated erythroid cells. In this study, we have examined whether unbalanced globin synthesis is expressed at all stages of human erythroid cell maturation. In order to determine the pattern of globin synthesis in early erythroid cells during erythroid cell maturation, an in vitro culture system using human bone marrow erythroid precursor cells has been developed. Early erythroid precursor cells (proerythroblasts and basophilic erythroblasts) have been isolated from nonthalassemic and thalassemic human bone marrows by lysing more mature erythroid cells, using complement and a rabbit antiserum prepared against normal human red cells. In the presence of erythropoietin, differentiation and proliferation of erythroid cells in demonstrable in liquid suspension culture for 24-48 hr, as determined by morphological criteria and by an increase in globin synthesis. The ratio of alpha- to beta-globin chain synthesis in nonthalassemic cells in approximately 1 at all stages of erythroid cell differentiation during culture. In cells from four patients with homozygous beta- thalassemia there is decreased beta-globin synthesis compared to alpha-globin synthesis, both in early erythroid precursor cells and during their maturation in culture. These findings indicate that unbalanced globin chain synthesis is expressed at all stages of red cell maturation in homozygous beta-thalassemia.", "contents": "Isolation and in vitro differentiation of human erythroid precursor cells. There is decreased beta-globin production in beta-thalassemic reticulocytes and nucleated erythroid cells. In this study, we have examined whether unbalanced globin synthesis is expressed at all stages of human erythroid cell maturation. In order to determine the pattern of globin synthesis in early erythroid cells during erythroid cell maturation, an in vitro culture system using human bone marrow erythroid precursor cells has been developed. Early erythroid precursor cells (proerythroblasts and basophilic erythroblasts) have been isolated from nonthalassemic and thalassemic human bone marrows by lysing more mature erythroid cells, using complement and a rabbit antiserum prepared against normal human red cells. In the presence of erythropoietin, differentiation and proliferation of erythroid cells in demonstrable in liquid suspension culture for 24-48 hr, as determined by morphological criteria and by an increase in globin synthesis. The ratio of alpha- to beta-globin chain synthesis in nonthalassemic cells in approximately 1 at all stages of erythroid cell differentiation during culture. In cells from four patients with homozygous beta- thalassemia there is decreased beta-globin synthesis compared to alpha-globin synthesis, both in early erythroid precursor cells and during their maturation in culture. These findings indicate that unbalanced globin chain synthesis is expressed at all stages of red cell maturation in homozygous beta-thalassemia."} {"id": "PMID:1260134", "title": "Separation of the erythropoietin-responsive progenitors BFU-E and CFU-E in mouse bone marrow by unit gravity sedimentation.", "content": "The sedimentation velocity profiles of the entities in mouse bone marrow responsible for erythropoietic burst formation (BFU-E) and for erythrocytic colony formation (CFU-E) have been studied under conditions designed to determine whether the values observed are real or result from cell interactions occurring during culture of the fractions. Bone marrow cells of adult C3Hf/Bi mice were subjected to unit gravity sedimentation in a bovine serum albumin gradient, and fractions were assayed in plasma culture. Because it was found that cell concentration affected the efficiency of erythropoietic burst formation in culture, aliquots were plated at two different cell concentrations, as well as at a fixed proportion of each fraction. The modal sedimentation velocity of the BFU-E population averaged 3.9 mm/hr and that of the CFU-E population, 6.4 mm/hr; both were found to be independent of cell concentration or method of dividing the fractions. Cells from fractions of different sedimentation velocity were mixed with one another or with unfractionated cells. No significant inhibition or stimulation of erythropoietic burst formation was seen. We concluded that the observed values represented the true modal sedimentation velocities of BFU-E and cfu-e in normal mice. To determine whether a change in the physiologic state of the animals affected the sedimentation velocities of BFU-E or CFU-E, marrow cells from mice hypertransfused with red cells were compared with those from controls. The modal sedimentation velocity of BFU-E was unaffected by hypertransfusion, nor was there any change in the number of BFU-E under these conditions. The number of CFU-E was substantially reduced without a significant change in modal sedimentation velocity.", "contents": "Separation of the erythropoietin-responsive progenitors BFU-E and CFU-E in mouse bone marrow by unit gravity sedimentation. The sedimentation velocity profiles of the entities in mouse bone marrow responsible for erythropoietic burst formation (BFU-E) and for erythrocytic colony formation (CFU-E) have been studied under conditions designed to determine whether the values observed are real or result from cell interactions occurring during culture of the fractions. Bone marrow cells of adult C3Hf/Bi mice were subjected to unit gravity sedimentation in a bovine serum albumin gradient, and fractions were assayed in plasma culture. Because it was found that cell concentration affected the efficiency of erythropoietic burst formation in culture, aliquots were plated at two different cell concentrations, as well as at a fixed proportion of each fraction. The modal sedimentation velocity of the BFU-E population averaged 3.9 mm/hr and that of the CFU-E population, 6.4 mm/hr; both were found to be independent of cell concentration or method of dividing the fractions. Cells from fractions of different sedimentation velocity were mixed with one another or with unfractionated cells. No significant inhibition or stimulation of erythropoietic burst formation was seen. We concluded that the observed values represented the true modal sedimentation velocities of BFU-E and cfu-e in normal mice. To determine whether a change in the physiologic state of the animals affected the sedimentation velocities of BFU-E or CFU-E, marrow cells from mice hypertransfused with red cells were compared with those from controls. The modal sedimentation velocity of BFU-E was unaffected by hypertransfusion, nor was there any change in the number of BFU-E under these conditions. The number of CFU-E was substantially reduced without a significant change in modal sedimentation velocity."} {"id": "PMID:1260135", "title": "Effect of vitamin B12 and folic acid deficiencies on neutrophil function.", "content": "Morphological and quantitative neutrophil abnormalities are common in the megaloblastic anemias of vitamin B12 and folic acid deficiency. Little is known, however, about the role of these vitamins in normal leukocyte function. Seven patients with megaloblastic bone marrows, four with vitamin B12 deficiency and three with folic acid deficiency, were studied to determine the effect, if any, of these deficiencies on leukocyte function. Phagocytosis of staphylococci, hexose monophosphate shunt activation with phagocytosis, and microbicidal capacity against Staphylococcus aureus were determined prior to the institution of specific therapy. In two instances, these studies were repeated following treatment. There was no impairment of phagocytosis per se, and resting metabolism was not significantly decreased. With phagocytosis, however, metabolic activation was decreased to 35%-36% of control values in the leukocytes of patients with vitamin B12 deficiency but not in the leukocytes of patients with folic acid deficiency. Bacterial killing was slightly decreased in vitamin B12 but not in folic acid deficiency. These abnormalities of function were reversed after specific therapy. These findings suggested a specific role for vitamin B12 in the production of intermediates necessary for normal cell function.", "contents": "Effect of vitamin B12 and folic acid deficiencies on neutrophil function. Morphological and quantitative neutrophil abnormalities are common in the megaloblastic anemias of vitamin B12 and folic acid deficiency. Little is known, however, about the role of these vitamins in normal leukocyte function. Seven patients with megaloblastic bone marrows, four with vitamin B12 deficiency and three with folic acid deficiency, were studied to determine the effect, if any, of these deficiencies on leukocyte function. Phagocytosis of staphylococci, hexose monophosphate shunt activation with phagocytosis, and microbicidal capacity against Staphylococcus aureus were determined prior to the institution of specific therapy. In two instances, these studies were repeated following treatment. There was no impairment of phagocytosis per se, and resting metabolism was not significantly decreased. With phagocytosis, however, metabolic activation was decreased to 35%-36% of control values in the leukocytes of patients with vitamin B12 deficiency but not in the leukocytes of patients with folic acid deficiency. Bacterial killing was slightly decreased in vitamin B12 but not in folic acid deficiency. These abnormalities of function were reversed after specific therapy. These findings suggested a specific role for vitamin B12 in the production of intermediates necessary for normal cell function."} {"id": "PMID:1260136", "title": "Pyruvate kinase deficiency and leg ulcers.", "content": "We report a family with a new pyruvate kinase (PK) variant in which leg ulcers have been present in four of the five affected homozygous family members, but not in any of the unaffected individuals. The propositus, an 18-yr-old boy, suffered from recurrent crises of hemolytic anemia and leg ulcers. A splenectomy was performed and the leg ulcer was treated un-successfully with a pinch graft. Studies ondialyzed hemolysates showed that the enzyme was kinetically abnorma, being almost entirely resistant to activation by fructose diphosphate. THE THERMOSTABILITY OF THE ENZYME WAS MODERATELY DECREASED, AND THE ELECTROPHORETIC MOBILITY WAS NORMAL. One may speculate that the development of leg ulcers in some kinships with PK deficiency may be related to variants of PK which exert unusual effects on the rheologic properties of the red cell in vivo.", "contents": "Pyruvate kinase deficiency and leg ulcers. We report a family with a new pyruvate kinase (PK) variant in which leg ulcers have been present in four of the five affected homozygous family members, but not in any of the unaffected individuals. The propositus, an 18-yr-old boy, suffered from recurrent crises of hemolytic anemia and leg ulcers. A splenectomy was performed and the leg ulcer was treated un-successfully with a pinch graft. Studies ondialyzed hemolysates showed that the enzyme was kinetically abnorma, being almost entirely resistant to activation by fructose diphosphate. THE THERMOSTABILITY OF THE ENZYME WAS MODERATELY DECREASED, AND THE ELECTROPHORETIC MOBILITY WAS NORMAL. One may speculate that the development of leg ulcers in some kinships with PK deficiency may be related to variants of PK which exert unusual effects on the rheologic properties of the red cell in vivo."} {"id": "PMID:1260137", "title": "Hemoglobin pyrgos alpha2 beta2 83 (EF7) Gly leads to Asp: a new hemoglobin variant in double heterozygosity with hemoglobin S.", "content": "An electrophoretically fast-moving hemoglobin variant was found to be present together with hemoglobin S, in the hemolysate of the rythrocytes of at 3-yr-old Greek boy. Electrophoresis of the parents' erythrocyte hemolysates revealed that the father was an AS heterozygote, while the mother was a carrier of the variant hemoglobin. A sibling was also found to be a carrier. The amount of the mutant hemoglobin in the peripheral blood of the propositus, his mother, and his brother was 62.2%, 52.5%, and 51.1%, respectively, as determined by column chromatography. The patients peripheral blood smear showed mild anisocytosis, microcytosis, and hypochromia. Similar but less pronounced red cell abnormalities were found in the other two carriers. Structural analysis of the variant hemoglobin revealed substitution of an aspartic acid for the glycine residue at the beta83 (EF7) position. This new hemoglobin was named hemoglobin Pyrgos. All the carriers of hemoglobin Pyrgos are clinically healthy, and there seems to be no interaction between hemoglobin Pyrgos and hemoglobin S as manifested clinically.", "contents": "Hemoglobin pyrgos alpha2 beta2 83 (EF7) Gly leads to Asp: a new hemoglobin variant in double heterozygosity with hemoglobin S. An electrophoretically fast-moving hemoglobin variant was found to be present together with hemoglobin S, in the hemolysate of the rythrocytes of at 3-yr-old Greek boy. Electrophoresis of the parents' erythrocyte hemolysates revealed that the father was an AS heterozygote, while the mother was a carrier of the variant hemoglobin. A sibling was also found to be a carrier. The amount of the mutant hemoglobin in the peripheral blood of the propositus, his mother, and his brother was 62.2%, 52.5%, and 51.1%, respectively, as determined by column chromatography. The patients peripheral blood smear showed mild anisocytosis, microcytosis, and hypochromia. Similar but less pronounced red cell abnormalities were found in the other two carriers. Structural analysis of the variant hemoglobin revealed substitution of an aspartic acid for the glycine residue at the beta83 (EF7) position. This new hemoglobin was named hemoglobin Pyrgos. All the carriers of hemoglobin Pyrgos are clinically healthy, and there seems to be no interaction between hemoglobin Pyrgos and hemoglobin S as manifested clinically."} {"id": "PMID:1260138", "title": "The effect of experimental hematoma on serum levels of fibrinogen-related antigen.", "content": "The effect of experimental hematomas on serum levels of fibrinogen-related antigen (FRA) was studied in rabbits. Homologous blood used for production of hematomas was mixed with 131I-fibrinogen, and the measurement of FRA was made using a radioactive technique (representing FRA from hematoma) and immunologically (representing total FRA). Total body radiation of animals bearing hematomas containing 131I-fibrinogen decayed slowly (mean t 1/2 = 189 hr) over the first 2-3 days and then rapidly (mean t 1/2 = 43 hr) during the subsequent days. Serum FRA levels measured immunologically rose transiently from 4 to 11 mug/ml during the slow phase of hematoma resolution, and returned to baseline levels during the rapid phase of resolution. The appearance of a small amount of protein-bound radioactivity in the blood of animals with hematomas paralleled the time course of the changes in immunologically determined FRA, but, even at its peak, circulating levels only averaged 0.36% of the administered tracer. From these observations, it seemed unlikely that the dissolution of fibrin which may form as the result of bleeding into tissues would significatnly contribute to levels of circulating FRA.", "contents": "The effect of experimental hematoma on serum levels of fibrinogen-related antigen. The effect of experimental hematomas on serum levels of fibrinogen-related antigen (FRA) was studied in rabbits. Homologous blood used for production of hematomas was mixed with 131I-fibrinogen, and the measurement of FRA was made using a radioactive technique (representing FRA from hematoma) and immunologically (representing total FRA). Total body radiation of animals bearing hematomas containing 131I-fibrinogen decayed slowly (mean t 1/2 = 189 hr) over the first 2-3 days and then rapidly (mean t 1/2 = 43 hr) during the subsequent days. Serum FRA levels measured immunologically rose transiently from 4 to 11 mug/ml during the slow phase of hematoma resolution, and returned to baseline levels during the rapid phase of resolution. The appearance of a small amount of protein-bound radioactivity in the blood of animals with hematomas paralleled the time course of the changes in immunologically determined FRA, but, even at its peak, circulating levels only averaged 0.36% of the administered tracer. From these observations, it seemed unlikely that the dissolution of fibrin which may form as the result of bleeding into tissues would significatnly contribute to levels of circulating FRA."} {"id": "PMID:1260143", "title": "Studies on the erythropoietic cell system in CBA mice after Rauscher virus infection.", "content": "Erythropoiesis in CBA mice was studied in Rauscher leukemia virus infected mice using the incorporation of 59Fe into spleen, bone marrow and peripheral blood. Beginning at day 4 an increased uptake into the spleen and a decrease in the bone marrow and the peripheral blood was observed. The increased uptake by the spleen was also found in plethoric mice. The erythropoietin responsive compartment was also enlarged in the spleen of these mice. The The dose-response-curve for erythropoietin was altered 4 days after infection, there was a higher background level of 59Fe incorporation and the response to low doses was better in infected animals. The reticulocytopenia which is usually seen in these mice, was overcome by administration of high doses of erythropoietin. It is concluded that the Rauscher virus acts in a similar manner to erythropoietin, but the erythropoiesis induced is ineffective since the cells do not mature. This maturation deficiency is influenced by administration of exogenous erythropoietin.", "contents": "Studies on the erythropoietic cell system in CBA mice after Rauscher virus infection. Erythropoiesis in CBA mice was studied in Rauscher leukemia virus infected mice using the incorporation of 59Fe into spleen, bone marrow and peripheral blood. Beginning at day 4 an increased uptake into the spleen and a decrease in the bone marrow and the peripheral blood was observed. The increased uptake by the spleen was also found in plethoric mice. The erythropoietin responsive compartment was also enlarged in the spleen of these mice. The The dose-response-curve for erythropoietin was altered 4 days after infection, there was a higher background level of 59Fe incorporation and the response to low doses was better in infected animals. The reticulocytopenia which is usually seen in these mice, was overcome by administration of high doses of erythropoietin. It is concluded that the Rauscher virus acts in a similar manner to erythropoietin, but the erythropoiesis induced is ineffective since the cells do not mature. This maturation deficiency is influenced by administration of exogenous erythropoietin."} {"id": "PMID:1260144", "title": "Iron storage in macrophages and endothelial cells. Histochemistry, ultrastructure, and clinical significance.", "content": "1 hour after i. v. infusion of colloidal iron in iron deficient subjects uniform phagosomal iron granules were observed in macrophages and endothelial cells of several organs. 7 to 10 days later transformation into ferritin coould be visualized in macrophages only. Now, these cells showed diffuse iron staining of the cytoplasm due to dispersed ferritin molecules. Polymorphous lysosomes contained densely packed particles from still unchanged ferric hydroxide to paracristalline ferritin. The macrophageal iron was mobilizable in few days to several weeks. The univorm lysosomal iron granules of endothelial cells disappeared after 1 to 2 years. Endothelial iron siderosis without previous i. v. iron application was a frequent finding in pernicious anaemia and iron overload of diverse origin.", "contents": "Iron storage in macrophages and endothelial cells. Histochemistry, ultrastructure, and clinical significance. 1 hour after i. v. infusion of colloidal iron in iron deficient subjects uniform phagosomal iron granules were observed in macrophages and endothelial cells of several organs. 7 to 10 days later transformation into ferritin coould be visualized in macrophages only. Now, these cells showed diffuse iron staining of the cytoplasm due to dispersed ferritin molecules. Polymorphous lysosomes contained densely packed particles from still unchanged ferric hydroxide to paracristalline ferritin. The macrophageal iron was mobilizable in few days to several weeks. The univorm lysosomal iron granules of endothelial cells disappeared after 1 to 2 years. Endothelial iron siderosis without previous i. v. iron application was a frequent finding in pernicious anaemia and iron overload of diverse origin."} {"id": "PMID:1260145", "title": "[Detection of reagent errors by internal quality control of the Coulter counter S].", "content": "By a simple program of quality control for the Coulter counter model S two deficient reagents could be detected. To high values of PCV associated with a decrease of MCHC were caused by a faulty Isoton batch. This error was revealed by native blood samples but not by the stabilized 4 C standard. Falsely elevated leukocyte counts due to insufficiently lysed giant platelets and platelet aggregates were produced by modified Lyse-S batches. Comparisons made with a Coulter counter model F using Zaponin and with a counting chamber yielded values at lower levels.", "contents": "[Detection of reagent errors by internal quality control of the Coulter counter S]. By a simple program of quality control for the Coulter counter model S two deficient reagents could be detected. To high values of PCV associated with a decrease of MCHC were caused by a faulty Isoton batch. This error was revealed by native blood samples but not by the stabilized 4 C standard. Falsely elevated leukocyte counts due to insufficiently lysed giant platelets and platelet aggregates were produced by modified Lyse-S batches. Comparisons made with a Coulter counter model F using Zaponin and with a counting chamber yielded values at lower levels."} {"id": "PMID:1260146", "title": "The response of dietary stressed Periplaneta americana to chronic intake of pure aflatoxin B.", "content": "In general these studies seem to indicate that adult male P. americana are not particularly sensitive, toxicologically, to aflatoxin B1, even when maintained on a marginally inadequate diet containing a low level of sucrose and no protein. Also they may be capable of detecting low levels of aflatoxin B1 in their diet (12 mug/ml) and seem not to concentrate aflatoxin B1 in their bodies. Even in dietary stressed conditions adult male American cockroaches showed a very limited potential as a bioassay organism for this toxin. Actually it appears that they may be quite resistant to the toxin. Currently there is no definite answer as to the advantages or disadvantages of insufficient dietary proteins or even carbohydrates providing protection against this toxin. The results show that the toxin would not be an effective cockroach-killing agent and thus could not serve as a bioassay system. However, this insect could serve as a model system in further investigating the mode of action and possible detoxification of aflatoxin B1.", "contents": "The response of dietary stressed Periplaneta americana to chronic intake of pure aflatoxin B. In general these studies seem to indicate that adult male P. americana are not particularly sensitive, toxicologically, to aflatoxin B1, even when maintained on a marginally inadequate diet containing a low level of sucrose and no protein. Also they may be capable of detecting low levels of aflatoxin B1 in their diet (12 mug/ml) and seem not to concentrate aflatoxin B1 in their bodies. Even in dietary stressed conditions adult male American cockroaches showed a very limited potential as a bioassay organism for this toxin. Actually it appears that they may be quite resistant to the toxin. Currently there is no definite answer as to the advantages or disadvantages of insufficient dietary proteins or even carbohydrates providing protection against this toxin. The results show that the toxin would not be an effective cockroach-killing agent and thus could not serve as a bioassay system. However, this insect could serve as a model system in further investigating the mode of action and possible detoxification of aflatoxin B1."} {"id": "PMID:1260149", "title": "Uptake and persistence of pesticides in cultured human cells.", "content": "The uptake and persistence of 14C-labeled pesticides in cultur-s of human embryonic lung diploid cells were studied. Chlordimeform, DDT, parathion, aldrin and dieldrin were selected as test compounds. Results obtained from these experiments divided the chemical into two groups. The first group consisted of three chemical DDT, aldrin and dieldrin which are generally classified as persistent insecticides while the second group was composed of chlordimeform and parathion, generally considered to be non-persistent insecticides. The rate of initial cellular incorporation of first group was approximately 20 to 70 times greater than the non-persistent insecticides. During the course of an incubation, the amounts of pesticide taken up by the cells decreased gradually.", "contents": "Uptake and persistence of pesticides in cultured human cells. The uptake and persistence of 14C-labeled pesticides in cultur-s of human embryonic lung diploid cells were studied. Chlordimeform, DDT, parathion, aldrin and dieldrin were selected as test compounds. Results obtained from these experiments divided the chemical into two groups. The first group consisted of three chemical DDT, aldrin and dieldrin which are generally classified as persistent insecticides while the second group was composed of chlordimeform and parathion, generally considered to be non-persistent insecticides. The rate of initial cellular incorporation of first group was approximately 20 to 70 times greater than the non-persistent insecticides. During the course of an incubation, the amounts of pesticide taken up by the cells decreased gradually."} {"id": "PMID:1260151", "title": "Effect of some inhibitors on aflatoxin-production in a synthetic medium and on the incorporation of acetate-1- 14C into aflatoxins by resting mycelia of Aspergillus parasiticus.", "content": "The effect of a number of metabolic inhibitors on the incorporation of acetate-1-14C into aflatoxins was investigated, using resting mycelia of Aspergillus parasiticus suspended in phosphate buffer. Malonate, iodoacetate, sodium arsenite, 2:4 dinitrophenol, sodium fluoride and p-aminosalicylate stimulated the incorporation at low concentrations and inhibited the same at high concentrations. p-Nitrobenzoic acid was inhibitory at all the concentrations tried. Fluoride, arsenite, arsenate and iodoacetate inhibited both growth and aflatoxin production when added directly to the growth medium. In general, there was a greater inhibition in growth medium than with the suspended mycelia.", "contents": "Effect of some inhibitors on aflatoxin-production in a synthetic medium and on the incorporation of acetate-1- 14C into aflatoxins by resting mycelia of Aspergillus parasiticus. The effect of a number of metabolic inhibitors on the incorporation of acetate-1-14C into aflatoxins was investigated, using resting mycelia of Aspergillus parasiticus suspended in phosphate buffer. Malonate, iodoacetate, sodium arsenite, 2:4 dinitrophenol, sodium fluoride and p-aminosalicylate stimulated the incorporation at low concentrations and inhibited the same at high concentrations. p-Nitrobenzoic acid was inhibitory at all the concentrations tried. Fluoride, arsenite, arsenate and iodoacetate inhibited both growth and aflatoxin production when added directly to the growth medium. In general, there was a greater inhibition in growth medium than with the suspended mycelia."} {"id": "PMID:1260153", "title": "Damage to spermatogenesis in juvenile rat treated with DDVP and malathion.", "content": "Juvenile male rats received either 20 mg DDVP or 40 mg malathion/kg on the 4th and 5th day of life, and either 10 mg DDVP or 20 mg/kg malathion daily from the 4th to the 23rd day of life. The histological examination of the testes showed slight reductions of the spermatogentic cells and Leydig cells. Therefore, it is assumed that testosterone synthesis is reduced, followed by damage to spermatogentic cells. All disturbances return by normal by the 50th day of life.", "contents": "Damage to spermatogenesis in juvenile rat treated with DDVP and malathion. Juvenile male rats received either 20 mg DDVP or 40 mg malathion/kg on the 4th and 5th day of life, and either 10 mg DDVP or 20 mg/kg malathion daily from the 4th to the 23rd day of life. The histological examination of the testes showed slight reductions of the spermatogentic cells and Leydig cells. Therefore, it is assumed that testosterone synthesis is reduced, followed by damage to spermatogentic cells. All disturbances return by normal by the 50th day of life."} {"id": "PMID:1260154", "title": "A study of inhalation of pentachlorophenol by rats III. Inhalation toxicity study.", "content": "An LD50 study of inhaled pentachlorophenol has been conducted. Seven groups of rats, consisting of 12 animals each, were exposed to the aerosol of sodium pentachlorophenate. The LD50 was 11.7 mg/kg body weight as shown on a probit curve.", "contents": "A study of inhalation of pentachlorophenol by rats III. Inhalation toxicity study. An LD50 study of inhaled pentachlorophenol has been conducted. Seven groups of rats, consisting of 12 animals each, were exposed to the aerosol of sodium pentachlorophenate. The LD50 was 11.7 mg/kg body weight as shown on a probit curve."} {"id": "PMID:1260155", "title": "A study of inhalation of pentachlorophenol by rats. IV. Distribution and excretion of inhaled pentachlorophenol.", "content": "It appears that in the rat repeated respiratory exposures to PCP do not result in an increase in the body burden of this compound as would be suspected from the 24 hour half-life determined from a single inhalation exposure. These results suggest some mechanism induced by prior exposure to PCP that increases the ability of the animals to remove this compound from its body. Increased excretion may be a factor in this activity, however, it cannot account for the total effect. Storage appears unlikely, since the elimination rate and time period remain unchanged after five doses as compared to after one. Increased matebolism may be the explanation, although this mechanism can only be inferred from these data. Quantitative metabolic results will be necessary to support this hypothesis.", "contents": "A study of inhalation of pentachlorophenol by rats. IV. Distribution and excretion of inhaled pentachlorophenol. It appears that in the rat repeated respiratory exposures to PCP do not result in an increase in the body burden of this compound as would be suspected from the 24 hour half-life determined from a single inhalation exposure. These results suggest some mechanism induced by prior exposure to PCP that increases the ability of the animals to remove this compound from its body. Increased excretion may be a factor in this activity, however, it cannot account for the total effect. Storage appears unlikely, since the elimination rate and time period remain unchanged after five doses as compared to after one. Increased matebolism may be the explanation, although this mechanism can only be inferred from these data. Quantitative metabolic results will be necessary to support this hypothesis."} {"id": "PMID:1260168", "title": "Reflex bradycardia and hypotension produced by prostaglandin F2alpha in the cat.", "content": "1 Intravenous administration of prostaglandin F2alpha results in a dose-dependent increase in pulmonary arterial pressure, decrease in systemic arterial pressure and a delayed bradycardia. Pulmonary vasoconstriction was observed at doses as low as 0.1 and 0.3 mug/kg. The systemic depressor and heart rate lowering effects were observed at 1 mug/kg doses and above. 2 A moderate bradycardia was still observed after atropine blockade but was abolished following bilateral vagotomy. Neither of these procedures affected the pulmonary vascular response. 3 Injections of submaximal doses of prostaglandin F2alpha (1--4 mug/kg) produced a greater and longer lasting bradycardia when injected into the left atrium than was observed following intravenous administration. In addition the latency of onset was much shorter following left atrial injection. These doses resulted in no change in heart rate and a minimal hypotension when injected into the brachiocephalic artery or into the aortic arch. 4 Small doses of prostaglandin F2alpha administered at the level of the origin of the coronary arteries produced marked decreases in heart rate and blood pressure whereas no change occurred following injection of the same amount into the ascending aorta at more distal sites. 5 These results suggest that prostaglandin F2alpha produces bradycardia and hypotension in the cat by activating 'receptors' located in the left heart or by acting on structures perfused by means of the coronary arteries.", "contents": "Reflex bradycardia and hypotension produced by prostaglandin F2alpha in the cat. 1 Intravenous administration of prostaglandin F2alpha results in a dose-dependent increase in pulmonary arterial pressure, decrease in systemic arterial pressure and a delayed bradycardia. Pulmonary vasoconstriction was observed at doses as low as 0.1 and 0.3 mug/kg. The systemic depressor and heart rate lowering effects were observed at 1 mug/kg doses and above. 2 A moderate bradycardia was still observed after atropine blockade but was abolished following bilateral vagotomy. Neither of these procedures affected the pulmonary vascular response. 3 Injections of submaximal doses of prostaglandin F2alpha (1--4 mug/kg) produced a greater and longer lasting bradycardia when injected into the left atrium than was observed following intravenous administration. In addition the latency of onset was much shorter following left atrial injection. These doses resulted in no change in heart rate and a minimal hypotension when injected into the brachiocephalic artery or into the aortic arch. 4 Small doses of prostaglandin F2alpha administered at the level of the origin of the coronary arteries produced marked decreases in heart rate and blood pressure whereas no change occurred following injection of the same amount into the ascending aorta at more distal sites. 5 These results suggest that prostaglandin F2alpha produces bradycardia and hypotension in the cat by activating 'receptors' located in the left heart or by acting on structures perfused by means of the coronary arteries."} {"id": "PMID:1260169", "title": "The effects of intra-amygdaloid injections of 6-hydroxy-dopamine on avoidance responding in rats.", "content": "1 The effects of bilateral intra-amygdaloid injections of 6-hydroxydopamine (6-OHDA) on shuttle box avoidance acquisition, retention, and extinction, and passive avoidance acquisition were examined in rats. 2 Intra amygdaloid 6-OHDA injections produced catecholamine depletion in and around the amygdalae but failed to reduce striatal dopamine concentrations. 3 Conditioned avoidance acquisition was markedly inhibited in 6-OHDA-treated rats whereas retention and extinction were only slightly impaired. 4 Passive avoidance acquisition was slightly but significantly improved in rats with amygdaloid 6-OHDA lesions. 5 Treated rats showed no motor abnormalities, they were not hypoactive in a photocell activity cage and they performed as well as controls on a rotating rod. 6 It is suggested that the conditioned avoidance acquisition deficit in rats with amygdaloid 6-OHDA lesions may be related to an impairment of associative learning rather than to perceptual or motor disturbances.", "contents": "The effects of intra-amygdaloid injections of 6-hydroxy-dopamine on avoidance responding in rats. 1 The effects of bilateral intra-amygdaloid injections of 6-hydroxydopamine (6-OHDA) on shuttle box avoidance acquisition, retention, and extinction, and passive avoidance acquisition were examined in rats. 2 Intra amygdaloid 6-OHDA injections produced catecholamine depletion in and around the amygdalae but failed to reduce striatal dopamine concentrations. 3 Conditioned avoidance acquisition was markedly inhibited in 6-OHDA-treated rats whereas retention and extinction were only slightly impaired. 4 Passive avoidance acquisition was slightly but significantly improved in rats with amygdaloid 6-OHDA lesions. 5 Treated rats showed no motor abnormalities, they were not hypoactive in a photocell activity cage and they performed as well as controls on a rotating rod. 6 It is suggested that the conditioned avoidance acquisition deficit in rats with amygdaloid 6-OHDA lesions may be related to an impairment of associative learning rather than to perceptual or motor disturbances."} {"id": "PMID:1260170", "title": "Effects of azaperone on cardiovascular and respiratory functions in the horse.", "content": "1 The butyrophenone tranquilizer, azaperone, was administered intramuscularly, at dose levels of 0.4 and 0.8 mg/kg, to ponies and its effects on cardiovascular and respiratory functions assessed. 2 Arterial blood pH, CO2 tension (PaCO2) and O2 tension (PaO2) remained relatively constant throughout the course of action of azaperone. 3 Azaperone did not modify plasma protein concentration but venous blood packed cell volume and haemoglobin concentration were reduced by 5 to 10% for at least 4 hours. These changes were probably caused by uptake of erythrocytes into the splenic reservoir. 4 Small increases in heart rate occurred for up to 60 min after administration of the drug, and this was followed by a slight bradycardia in some ponies. 5 Azaperone reduced mean arterial blood pressure (MAP) for at least 4 h, by which time its ataractic action was generally no longer apparent. The hypotension was caused, during the early phase of action at least, by a reduction in peripheral resistance, since cardiac output was increased slightly 20 min after its administration. Possible mechanisms underlying the cardiovascular changes are discussed. 6 In spite of reductions in arterial blood O2 content and MAP produced by azaperone, it is likely that tissue oxygenation was adequate, since arterial blood lactate concentrations were not increased.", "contents": "Effects of azaperone on cardiovascular and respiratory functions in the horse. 1 The butyrophenone tranquilizer, azaperone, was administered intramuscularly, at dose levels of 0.4 and 0.8 mg/kg, to ponies and its effects on cardiovascular and respiratory functions assessed. 2 Arterial blood pH, CO2 tension (PaCO2) and O2 tension (PaO2) remained relatively constant throughout the course of action of azaperone. 3 Azaperone did not modify plasma protein concentration but venous blood packed cell volume and haemoglobin concentration were reduced by 5 to 10% for at least 4 hours. These changes were probably caused by uptake of erythrocytes into the splenic reservoir. 4 Small increases in heart rate occurred for up to 60 min after administration of the drug, and this was followed by a slight bradycardia in some ponies. 5 Azaperone reduced mean arterial blood pressure (MAP) for at least 4 h, by which time its ataractic action was generally no longer apparent. The hypotension was caused, during the early phase of action at least, by a reduction in peripheral resistance, since cardiac output was increased slightly 20 min after its administration. Possible mechanisms underlying the cardiovascular changes are discussed. 6 In spite of reductions in arterial blood O2 content and MAP produced by azaperone, it is likely that tissue oxygenation was adequate, since arterial blood lactate concentrations were not increased."} {"id": "PMID:1260171", "title": "Blood pressure responses to adrenal field stimulation as a measure of adrenal catecholamine release.", "content": "1 A new method for studying adrenal medullary release is described in pithed rats using field stimulation of an entire adrenal gland. 2 The increases in blood pressure in response to field stimulation of the gland consisted of an initial short, variable component, due to stimulation of adrenergic vasomotor neurones and a secondary, longer lasting component, due to medullary catecholamine release. 3 Removal of the initial component by drugs or cardiac/coeliac ganglionectomy did not affect the magnitude of the secondary pressor component. 4 The secondary pressor component was frequency-dependent, reproducible and stable with time. The extent of medullary catecholamine release could be assessed by comparing the blood pressure rise with those obtained after adrenaline injections. 5 The method appears to provide a reliable means by which adrenal medullary catecholamine release may be assessed without significant interference from vasomotor nerves.", "contents": "Blood pressure responses to adrenal field stimulation as a measure of adrenal catecholamine release. 1 A new method for studying adrenal medullary release is described in pithed rats using field stimulation of an entire adrenal gland. 2 The increases in blood pressure in response to field stimulation of the gland consisted of an initial short, variable component, due to stimulation of adrenergic vasomotor neurones and a secondary, longer lasting component, due to medullary catecholamine release. 3 Removal of the initial component by drugs or cardiac/coeliac ganglionectomy did not affect the magnitude of the secondary pressor component. 4 The secondary pressor component was frequency-dependent, reproducible and stable with time. The extent of medullary catecholamine release could be assessed by comparing the blood pressure rise with those obtained after adrenaline injections. 5 The method appears to provide a reliable means by which adrenal medullary catecholamine release may be assessed without significant interference from vasomotor nerves."} {"id": "PMID:1260172", "title": "Rat uterus renin-like activity: effect of stimuli and hormones.", "content": "1 The characteristics of renin-like activity in rat uterus were studied. The optimum temperature was 50 degrees C and optimum pH 4.0. Potassium (100 mM) enhanced this activity but sodium or calcium had no effect. 2 Uterine renin-like activity was unchanged 24 h after bilateral nephrectomy. 3 Renin-like activity in the uterus increased slowly from birth to 4 weeks of age and faster between the 4th and 8th week. 4 Ovariectomy caused a considerable fall in uterine renin-like activity. 5 The following factors, known to affect renin secretion in the kidney, i.e., hypovolaemia, sodium loading, adrenalectomy, administration of desoxycorticosterone acetate and injection of isoprenaline, had no effect on uterine renin-like activity. 6 Stilboestrol, an oestrogen, caused a significant increase of uterine renin-like activity. Progesterone and testosterone had no significant effect on this activity but blocked the increase caused by stilboestrol. 7 During pregnancy there was a small but significant fall of renin-like activity in the uterus in the first week and a continuous increase throughout the later period of pregnancy. 8 It is concluded that uterine renin-like activity is independent of kidney renin and does not respond to stimuli affecting kidney renin. Uterine renin activity is hormone-dependent and may be governed by the ratio, oestrogen : progesterone.", "contents": "Rat uterus renin-like activity: effect of stimuli and hormones. 1 The characteristics of renin-like activity in rat uterus were studied. The optimum temperature was 50 degrees C and optimum pH 4.0. Potassium (100 mM) enhanced this activity but sodium or calcium had no effect. 2 Uterine renin-like activity was unchanged 24 h after bilateral nephrectomy. 3 Renin-like activity in the uterus increased slowly from birth to 4 weeks of age and faster between the 4th and 8th week. 4 Ovariectomy caused a considerable fall in uterine renin-like activity. 5 The following factors, known to affect renin secretion in the kidney, i.e., hypovolaemia, sodium loading, adrenalectomy, administration of desoxycorticosterone acetate and injection of isoprenaline, had no effect on uterine renin-like activity. 6 Stilboestrol, an oestrogen, caused a significant increase of uterine renin-like activity. Progesterone and testosterone had no significant effect on this activity but blocked the increase caused by stilboestrol. 7 During pregnancy there was a small but significant fall of renin-like activity in the uterus in the first week and a continuous increase throughout the later period of pregnancy. 8 It is concluded that uterine renin-like activity is independent of kidney renin and does not respond to stimuli affecting kidney renin. Uterine renin activity is hormone-dependent and may be governed by the ratio, oestrogen : progesterone."} {"id": "PMID:1260173", "title": "A method for recording smooth muscle and vascular responses of the blood-perfused dog trachea in situ.", "content": "1 A method is described for measuring responses of dog tracheal musculature and vasculature in situ. 2 The upper two thirds of the trachea was perfused with blood through both cranial thyroid arteries at a constant pressure. The blood flow through the arteries was measured with an electromagnetic flowmeter. The response of the tracheal musculature was measured as a change in pressure in a water-filled cuff inserted into the trachea via the mouth. Drugs were injected close-arterially. 3 Acetylcholine produced dose-dependent increases in blood flow rate (vasodilatation) and in tracheal intraluminal pressure (tracheal constriction). These responses were antagonized by atropine. 4 Isoprenaline produced vasodilatation which was blocked by propranolol. Adrenaline and noradrenaline caused vasocontriction which was blocked by phentolamine. 5 All three catecholamines produced a decrease in tracheal intraluminal pressure (tracheal dilatation). The tracheal dilatation in response to adrenaline and noradrenaline was converted to constriction by propranolol. The tracheal constriction thus unmasked was abolished specifically by phentolamine. 6 From these results it is concluded that the tracheal musculature and vasculature contain muscarinic receptors, and excitatory alpha- and inhibitory beta-adrenoceptors. In the tracheal musculature beta-adrenoceptors predominate over alpha-adrenoceptors; the reverse is true in the tracheal vasculature.", "contents": "A method for recording smooth muscle and vascular responses of the blood-perfused dog trachea in situ. 1 A method is described for measuring responses of dog tracheal musculature and vasculature in situ. 2 The upper two thirds of the trachea was perfused with blood through both cranial thyroid arteries at a constant pressure. The blood flow through the arteries was measured with an electromagnetic flowmeter. The response of the tracheal musculature was measured as a change in pressure in a water-filled cuff inserted into the trachea via the mouth. Drugs were injected close-arterially. 3 Acetylcholine produced dose-dependent increases in blood flow rate (vasodilatation) and in tracheal intraluminal pressure (tracheal constriction). These responses were antagonized by atropine. 4 Isoprenaline produced vasodilatation which was blocked by propranolol. Adrenaline and noradrenaline caused vasocontriction which was blocked by phentolamine. 5 All three catecholamines produced a decrease in tracheal intraluminal pressure (tracheal dilatation). The tracheal dilatation in response to adrenaline and noradrenaline was converted to constriction by propranolol. The tracheal constriction thus unmasked was abolished specifically by phentolamine. 6 From these results it is concluded that the tracheal musculature and vasculature contain muscarinic receptors, and excitatory alpha- and inhibitory beta-adrenoceptors. In the tracheal musculature beta-adrenoceptors predominate over alpha-adrenoceptors; the reverse is true in the tracheal vasculature."} {"id": "PMID:1260174", "title": "Impaired absorption of chlorpromazine in rats given trihexyphenidyl.", "content": "1 The absorption and tissue distribution of orally administered [14C]-chlorpromazine (CPZ) were compared in trihexyphenidyl (THP; Artane)-treated and control rats. 2 Total radioactivity (CPZ) in the plasma and brain of rats treated with THP was significantly lower whereas total radioactivity in the stomach was significantly higher than in rats not previously treated with THP. 3 Gastric emptying in rats treated with THP was significantly delayed as measured by gastric clearance of a marker [14C]-polyethylene glycol. 4 Transport of [14C]-CPZ in everted sacs was not affected by treatment with THP. 5 Metabolism of [14C]-CPZ by liver homogenates was not affected by treatment with THP. 6 The relationship of delayed gastric emptying in THP-treated rats and their lower plasma and brain levels of [14C]-CPZ after oral administration is discussed.", "contents": "Impaired absorption of chlorpromazine in rats given trihexyphenidyl. 1 The absorption and tissue distribution of orally administered [14C]-chlorpromazine (CPZ) were compared in trihexyphenidyl (THP; Artane)-treated and control rats. 2 Total radioactivity (CPZ) in the plasma and brain of rats treated with THP was significantly lower whereas total radioactivity in the stomach was significantly higher than in rats not previously treated with THP. 3 Gastric emptying in rats treated with THP was significantly delayed as measured by gastric clearance of a marker [14C]-polyethylene glycol. 4 Transport of [14C]-CPZ in everted sacs was not affected by treatment with THP. 5 Metabolism of [14C]-CPZ by liver homogenates was not affected by treatment with THP. 6 The relationship of delayed gastric emptying in THP-treated rats and their lower plasma and brain levels of [14C]-CPZ after oral administration is discussed."} {"id": "PMID:1260175", "title": "Benzodiazepines and central glycine receptors.", "content": "1 In cats, anaesthetized with pentobarbitone, intravenous diazepam (minimum dose 3.0 mg/kg) enhanced dorsal root potentials but did not significantly diminish the reduction by electrophoretic strychnine of the inhibitory action of electrophoretic glycine on dorsal horn interneurones. 2 In mice, intraperitoneal diazepam (2.5 mg/kg) had no appreciable effect on the potency of strychnine as a convulsant, although providing some protection against bicuculline. 3 These observations, together with the failure of chlordiazepoxide to either inhibit the firing of spinal interneurones or reduce antagonism between strychnine and glycine when administered locally, provide no support for the interaction between benzodiazepines and mammalian central glycine receptors which has been proposed on the basis of in vitro studies of strychnine binding.", "contents": "Benzodiazepines and central glycine receptors. 1 In cats, anaesthetized with pentobarbitone, intravenous diazepam (minimum dose 3.0 mg/kg) enhanced dorsal root potentials but did not significantly diminish the reduction by electrophoretic strychnine of the inhibitory action of electrophoretic glycine on dorsal horn interneurones. 2 In mice, intraperitoneal diazepam (2.5 mg/kg) had no appreciable effect on the potency of strychnine as a convulsant, although providing some protection against bicuculline. 3 These observations, together with the failure of chlordiazepoxide to either inhibit the firing of spinal interneurones or reduce antagonism between strychnine and glycine when administered locally, provide no support for the interaction between benzodiazepines and mammalian central glycine receptors which has been proposed on the basis of in vitro studies of strychnine binding."} {"id": "PMID:1260176", "title": "Studies on the relative effects of prostaglandins, bradykinin, 5-hydroxytryptamine and histamine on the synovial microcirculation in dogs.", "content": "1 The relative effects of prostaglandins E1, E2, F1alpha, F2alpha, bradykinin, histamine and 5-hydroxytryptamine (5-HT) on the canine synovial microcirculation were investigated using the rate of clearance of radioactive xenon (133Xe) as an index of synovial perfusion. 2 All the compounds tested, except prostaglandin F1alpha, produced a vasodilator effect. The descending order of potency of the active compounds was (i) prostaglandin E1, (ii) prostaglandin E2 and bradykinin, (iii) histamine and 5-HT, (iv) prostaglandin F2alpha. The most potent compound tested, prostaglandin E1 produced an effect in nanogram amounts in each joint. 3 Prostaglandin F2alpha has been reported to have an anti-inflammatory action; however no evidence was found of antagonism of prostaglandin E1 by two dose levels of prostaglandin F2alpha. 4 Preliminary studies showed that threshold doses of prostaglandin E1 did not potentiate the vasodilator action of threshold or sub-threshold doses of bradykinin in the dog synovium.", "contents": "Studies on the relative effects of prostaglandins, bradykinin, 5-hydroxytryptamine and histamine on the synovial microcirculation in dogs. 1 The relative effects of prostaglandins E1, E2, F1alpha, F2alpha, bradykinin, histamine and 5-hydroxytryptamine (5-HT) on the canine synovial microcirculation were investigated using the rate of clearance of radioactive xenon (133Xe) as an index of synovial perfusion. 2 All the compounds tested, except prostaglandin F1alpha, produced a vasodilator effect. The descending order of potency of the active compounds was (i) prostaglandin E1, (ii) prostaglandin E2 and bradykinin, (iii) histamine and 5-HT, (iv) prostaglandin F2alpha. The most potent compound tested, prostaglandin E1 produced an effect in nanogram amounts in each joint. 3 Prostaglandin F2alpha has been reported to have an anti-inflammatory action; however no evidence was found of antagonism of prostaglandin E1 by two dose levels of prostaglandin F2alpha. 4 Preliminary studies showed that threshold doses of prostaglandin E1 did not potentiate the vasodilator action of threshold or sub-threshold doses of bradykinin in the dog synovium."} {"id": "PMID:1260177", "title": "The effects of prostaglandins E1, E2 and F2alpha on the cutaneous vasculature of the rat.", "content": "1 The responses of the rat cutaneous vasculature to prostaglandins E1, E2 and F2alpha have been investigated by a photomicrographic technique. 2 Prostaglandin E1 produced transient arterial constriction which was blocked by local pretreatment of preparations with compound 48/80 or methysergide. It was concluded that prostaglandin E1 produced vasoconstriction by release of 5-hydroxytryptamine (5-HT) from mast cells. The magnitude of the vasoconstrictor response appeared to be subject to seasonal variation. 3 Prostaglandin F2alpha produced arterial constriction of longer duration which was not blocked by compound 48/80, methysergide or phenoxybenzamine. 4 Preparations pretreated with prostaglandin F2alpha were found to be more sensitive to the venous constrictor effect, and less sensitive to the arterial constrictor effect, of noradrenaline. 5 Prostaglandin E2 produced arterial constriction which was usually partially blocked by compound 48/80 and methysergide and it was concluded that a major component of the vasoconstrictor response to prostaglandin E2 was of the E1 type but some component was of the F2alpha type.", "contents": "The effects of prostaglandins E1, E2 and F2alpha on the cutaneous vasculature of the rat. 1 The responses of the rat cutaneous vasculature to prostaglandins E1, E2 and F2alpha have been investigated by a photomicrographic technique. 2 Prostaglandin E1 produced transient arterial constriction which was blocked by local pretreatment of preparations with compound 48/80 or methysergide. It was concluded that prostaglandin E1 produced vasoconstriction by release of 5-hydroxytryptamine (5-HT) from mast cells. The magnitude of the vasoconstrictor response appeared to be subject to seasonal variation. 3 Prostaglandin F2alpha produced arterial constriction of longer duration which was not blocked by compound 48/80, methysergide or phenoxybenzamine. 4 Preparations pretreated with prostaglandin F2alpha were found to be more sensitive to the venous constrictor effect, and less sensitive to the arterial constrictor effect, of noradrenaline. 5 Prostaglandin E2 produced arterial constriction which was usually partially blocked by compound 48/80 and methysergide and it was concluded that a major component of the vasoconstrictor response to prostaglandin E2 was of the E1 type but some component was of the F2alpha type."} {"id": "PMID:1260178", "title": "A comparison of gamma-aminobutyric acid and the semi-rigid analogues 4-aminotetrolic acid, 4-aminocrotonic acid and imidazole-4-acetic acid on the isolated superior cervical ganglion of the rat.", "content": "1 The rat superior cervical ganglion possesses receptors for gamma-aminobutyric acid (GABA). This can be demonstrated in vitro by recording the changes in ganglionic surface potential which occur after the addition of GABA to the bathing solution. 2 The action of three conformationally-restricted analogues of GABA namely 4-aminotetrolic acid (4-ATA), trans 4-aminocrotonic acid (4-ACA) and imidazole-4-acetic acid (IAA) have been examined for activity at this peripheral receptor. 3 All three analogues depolarized the ganglion in a manner similar to GABA. Their actions were transient and were 'occluded' by GABA; also the dose-response curve in each case was parallel to that of GABA. Molar potencies relative to GABA (= 1) were 4-ACA = 1.48, IAA = 0.100, 4-ATA = 0.0028. 4 The action of each analogue could be blocked by the GABA antagonists bicuculline and tetramethylenedisulphotetramine at doses which had relatively little effect on responses to the cholinomimetic carbachol. 5 4-ACA and IAA (1 mM) significantly reduced the ganglionic accumulation of [3H]-GABA (0.2 muM) by 88% and 58% respectively whereas 4-ATA (1 mM), caused no significant reduction in [3H]-GABA accumulation.", "contents": "A comparison of gamma-aminobutyric acid and the semi-rigid analogues 4-aminotetrolic acid, 4-aminocrotonic acid and imidazole-4-acetic acid on the isolated superior cervical ganglion of the rat. 1 The rat superior cervical ganglion possesses receptors for gamma-aminobutyric acid (GABA). This can be demonstrated in vitro by recording the changes in ganglionic surface potential which occur after the addition of GABA to the bathing solution. 2 The action of three conformationally-restricted analogues of GABA namely 4-aminotetrolic acid (4-ATA), trans 4-aminocrotonic acid (4-ACA) and imidazole-4-acetic acid (IAA) have been examined for activity at this peripheral receptor. 3 All three analogues depolarized the ganglion in a manner similar to GABA. Their actions were transient and were 'occluded' by GABA; also the dose-response curve in each case was parallel to that of GABA. Molar potencies relative to GABA (= 1) were 4-ACA = 1.48, IAA = 0.100, 4-ATA = 0.0028. 4 The action of each analogue could be blocked by the GABA antagonists bicuculline and tetramethylenedisulphotetramine at doses which had relatively little effect on responses to the cholinomimetic carbachol. 5 4-ACA and IAA (1 mM) significantly reduced the ganglionic accumulation of [3H]-GABA (0.2 muM) by 88% and 58% respectively whereas 4-ATA (1 mM), caused no significant reduction in [3H]-GABA accumulation."} {"id": "PMID:1260179", "title": "Investigation of occurrence of tolerance to bronchodilator drugs in chronically pretreated guinea-pigs.", "content": "1 The actions of sympathomimetic amines on isolated preparations of atria, trachea and ileum were studied in vitro in guinea-pigs, which had been pretreated for 5 or 12 days, by subcutaneous injection, with adrenaline (5 mug/kg), salbutamol (0.5 mug/kg), salbutamol (0.5 mug/kg), methoxamine (250 mug/kg) or saline (0.9% w/V NaCl solution). 2 In the trachea, a decrease in sensitivity (tolerance) to the relaxant effect of adrenaline was induced by pretreatment, for 12 but not for 5 days, with adrenaline. In these animals, cross-tolerance to isoprenaline or salbutamol was not observed. Tolerance to the relaxant actions of adrenaline isoprenaline or salbutamol was not observed after pretreatment with salbutamol. 3 In the trachea, pretreatment with methoxamine or adrenaline for 12 days did not change the sensitivity to the alpha-adrenoceptor-mediated contractor action of methoxamine. 4 In the atria from those guinea-pigs pretreated with adrenaline or salbutamol, there was no reduced sensitivity to the beta-adrenoceptor agonist actions of adrenaline, isoprenaline or salbutamol. In animals pretreated with methoxamine or adrenaline, there was no observable tolerance or cross tolerance to methoxamine with respect to its alpha-adrenoceptor-mediated positive inotropic action in the atria and no unequivocal evidence of a reduced sensitivity to that action of adrenaline. 5 It was confirmed that the twitch-like contractions of the longitudinal muscle of the electrically stimulated ileum were inhibited by sympatomimetic amines acting on alpha- and beta-adrenoceptors. There was no reduced sensitivity to the inhibitory actions of noradrenaline or isoprenaline on the twitch of ileum isolated from animals pretreated with adrenaline, salbutamol or methoxamine for 5 or 12 days. 6 From our results on these three preparations from the same animals, it is concluded that generalizations regarding changes in sensitivity to sympathomimetic amines following their prolonged administration should not be made in any one species.", "contents": "Investigation of occurrence of tolerance to bronchodilator drugs in chronically pretreated guinea-pigs. 1 The actions of sympathomimetic amines on isolated preparations of atria, trachea and ileum were studied in vitro in guinea-pigs, which had been pretreated for 5 or 12 days, by subcutaneous injection, with adrenaline (5 mug/kg), salbutamol (0.5 mug/kg), salbutamol (0.5 mug/kg), methoxamine (250 mug/kg) or saline (0.9% w/V NaCl solution). 2 In the trachea, a decrease in sensitivity (tolerance) to the relaxant effect of adrenaline was induced by pretreatment, for 12 but not for 5 days, with adrenaline. In these animals, cross-tolerance to isoprenaline or salbutamol was not observed. Tolerance to the relaxant actions of adrenaline isoprenaline or salbutamol was not observed after pretreatment with salbutamol. 3 In the trachea, pretreatment with methoxamine or adrenaline for 12 days did not change the sensitivity to the alpha-adrenoceptor-mediated contractor action of methoxamine. 4 In the atria from those guinea-pigs pretreated with adrenaline or salbutamol, there was no reduced sensitivity to the beta-adrenoceptor agonist actions of adrenaline, isoprenaline or salbutamol. In animals pretreated with methoxamine or adrenaline, there was no observable tolerance or cross tolerance to methoxamine with respect to its alpha-adrenoceptor-mediated positive inotropic action in the atria and no unequivocal evidence of a reduced sensitivity to that action of adrenaline. 5 It was confirmed that the twitch-like contractions of the longitudinal muscle of the electrically stimulated ileum were inhibited by sympatomimetic amines acting on alpha- and beta-adrenoceptors. There was no reduced sensitivity to the inhibitory actions of noradrenaline or isoprenaline on the twitch of ileum isolated from animals pretreated with adrenaline, salbutamol or methoxamine for 5 or 12 days. 6 From our results on these three preparations from the same animals, it is concluded that generalizations regarding changes in sensitivity to sympathomimetic amines following their prolonged administration should not be made in any one species."} {"id": "PMID:1260219", "title": "Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats.", "content": "1 The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. 2 No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. 3 The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. 4 Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion.", "contents": "Lithium orotate, carbonate and chloride: pharmacokinetics, polyuria in rats. 1 The pharmacokinetics of the lithium ion administered as lithium orotate were studied in rats. Parallel studies were carried out with lithium carbonate and lithium chloride. 2 No differences in the uptake, distribution and excretion of the lithium ion were observed between lithium orotate, lithium carbonate and lithium chloride after single intraperitoneal, subcutaneous or intragastric injections (0.5-1.0 mEq lithium/kg) or after administration of the lithium salts for 20 days in the food. 3 The findings oppose the notion that the pharmacokinetics of the lithium ion given as lithium orotate differ from lithium chloride or lithium carbonate. 4 Polyuria and polydipsia developed more slowly in rats given lithium orotate than in those given lithium carbonate or lithium chloride, perhaps due to an effect of the orotate anion."} {"id": "PMID:1260220", "title": "The uptake of tritiated delta 1-tetrahydrocannabinol by the isolated vas deferens of the rat.", "content": "1 Weighed stripped vasa deferentia were incubated in Holman's solution containing (a) [14C]-sorbitol 0.014 mm, (b) [3H]-noradrenaline ([3H]-NA) 12.31 nM, (c) [3H]-tetrahydrocannabinol ([3H]-delta1-THC) 1 mug/ml for 5, 10, 20 and 30 minutes. 2 Tissues were washed, dissolved in Protosol, counted by standard scintillation counting technique and 'drug space' expressed as ct min-1 mg-1 tissue/ct min-l mul-1 bathing fluid. 3 Vasa incubated for 30 min with [14C]-sorbitol were washed for varying lengths of time; 82% clearance had taken place after 2 washes of 5 minutes. 4 The uptake of [3H]-NA was inhibited by the presence of desmethylimipramine (DMI) 10 nM in the bath or by pretreatment of rats with 6-hydroxydopamine (6-OHDA). 5 The uptake of [3H]-delta 1-THC was not inhibited by the presence of DMI. It was reduced but not abolished by 6-OHDA pretreatment.", "contents": "The uptake of tritiated delta 1-tetrahydrocannabinol by the isolated vas deferens of the rat. 1 Weighed stripped vasa deferentia were incubated in Holman's solution containing (a) [14C]-sorbitol 0.014 mm, (b) [3H]-noradrenaline ([3H]-NA) 12.31 nM, (c) [3H]-tetrahydrocannabinol ([3H]-delta1-THC) 1 mug/ml for 5, 10, 20 and 30 minutes. 2 Tissues were washed, dissolved in Protosol, counted by standard scintillation counting technique and 'drug space' expressed as ct min-1 mg-1 tissue/ct min-l mul-1 bathing fluid. 3 Vasa incubated for 30 min with [14C]-sorbitol were washed for varying lengths of time; 82% clearance had taken place after 2 washes of 5 minutes. 4 The uptake of [3H]-NA was inhibited by the presence of desmethylimipramine (DMI) 10 nM in the bath or by pretreatment of rats with 6-hydroxydopamine (6-OHDA). 5 The uptake of [3H]-delta 1-THC was not inhibited by the presence of DMI. It was reduced but not abolished by 6-OHDA pretreatment."} {"id": "PMID:1260221", "title": "Uptake of 5-hydroxytryptamine by rat blood platelets and its inhibition by adenosine 5'-diphosphate.", "content": "1 The uptake of 5-hydroxytryptamine (5-HT) by rat blood platelets in citrated plasma was linear for at most 10 s and was substantially complete within 3 minutes. 2 Adenosine 5'-diphosphate (ADP) was a potent inhibitor of 5-HT uptake (Ki=0.38 muM) and kinetic analysis revealed that the inhibition was not competitive. 3 Inhibition of 5-HT uptake by ADP was abolished in the presence of prostaglandin E1 and 2-n-amylthio-AMP, which also inhibit the stimulant actions of ADP on blood platelets. 4 It is concluded that ADP could inhibit 5-HT uptake by changing the Na+/K+ distribution across the cell membrane, and the biological significance of this is discussed.", "contents": "Uptake of 5-hydroxytryptamine by rat blood platelets and its inhibition by adenosine 5'-diphosphate. 1 The uptake of 5-hydroxytryptamine (5-HT) by rat blood platelets in citrated plasma was linear for at most 10 s and was substantially complete within 3 minutes. 2 Adenosine 5'-diphosphate (ADP) was a potent inhibitor of 5-HT uptake (Ki=0.38 muM) and kinetic analysis revealed that the inhibition was not competitive. 3 Inhibition of 5-HT uptake by ADP was abolished in the presence of prostaglandin E1 and 2-n-amylthio-AMP, which also inhibit the stimulant actions of ADP on blood platelets. 4 It is concluded that ADP could inhibit 5-HT uptake by changing the Na+/K+ distribution across the cell membrane, and the biological significance of this is discussed."} {"id": "PMID:1260222", "title": "The distribution and kinetics of sulphacetamide in leukaemic mice.", "content": "1 During the first 90 min following oral administration of sulphacetamide, there was a rapid decline in plasma drug concentration in control mice whereas a progressive increase in sulphacetamide concentration was observed in leukaemic mice. 2 Similar changes in the kinetics of sulphacetamide distribution were observed in the liver, spleen and muscle. 3 While the concentration of sulphacetamide remained quite constant in the brain and fat tissue of control mice, a progressive increase in drug concentration was observed in the brain and fat tissue of leukaemic mice. 4 Some of these changes in the kinetics of sulphacetamide tissue distribution are compatible with delay in gastrointestinal absorption of the drug and its accumulation in the ascitic fluid.", "contents": "The distribution and kinetics of sulphacetamide in leukaemic mice. 1 During the first 90 min following oral administration of sulphacetamide, there was a rapid decline in plasma drug concentration in control mice whereas a progressive increase in sulphacetamide concentration was observed in leukaemic mice. 2 Similar changes in the kinetics of sulphacetamide distribution were observed in the liver, spleen and muscle. 3 While the concentration of sulphacetamide remained quite constant in the brain and fat tissue of control mice, a progressive increase in drug concentration was observed in the brain and fat tissue of leukaemic mice. 4 Some of these changes in the kinetics of sulphacetamide tissue distribution are compatible with delay in gastrointestinal absorption of the drug and its accumulation in the ascitic fluid."} {"id": "PMID:1260223", "title": "Effects of mazindol, a non-phenylethylamine anorexigenic agent, on biogenic amine levels and turnover rate.", "content": "1 Mazindol is a new anorexigenic agent which possesses a different chemical structure from that of phenylethylamines, but shows a pharmacological profile similar to that of (+)-amphetamine. 2 Mazindol neither altered whole brain monoamine levels (noradrenaline (NA), dopamine, 5-hydroxytryptamine (5-HT)) nor changed NA levels in the hypothalamus or dopamine levels in the caudate nucleus. 3 Mazindol enhanced dopamine turnover rate in the caudate nucleus, as shown by the increased rate of dopamine decline after blockade of catecholamine synthesis by alpha-methyl-p-tyrosine and decreased the conversion index of (3H)-tyrosine into brain NA. 4 Mazindol administration did not modify pargyline-induced decline of 5-hydroxyindoleacetic acid suggesting that 5-HT turnover is not altered by this drug.", "contents": "Effects of mazindol, a non-phenylethylamine anorexigenic agent, on biogenic amine levels and turnover rate. 1 Mazindol is a new anorexigenic agent which possesses a different chemical structure from that of phenylethylamines, but shows a pharmacological profile similar to that of (+)-amphetamine. 2 Mazindol neither altered whole brain monoamine levels (noradrenaline (NA), dopamine, 5-hydroxytryptamine (5-HT)) nor changed NA levels in the hypothalamus or dopamine levels in the caudate nucleus. 3 Mazindol enhanced dopamine turnover rate in the caudate nucleus, as shown by the increased rate of dopamine decline after blockade of catecholamine synthesis by alpha-methyl-p-tyrosine and decreased the conversion index of (3H)-tyrosine into brain NA. 4 Mazindol administration did not modify pargyline-induced decline of 5-hydroxyindoleacetic acid suggesting that 5-HT turnover is not altered by this drug."} {"id": "PMID:1260224", "title": "The uptake and subcellular distribution of radio-labelled metabolites of digitoxin in the guinea-pig isolated perfused heart.", "content": "1 Comparisons were made of the uptake and inotropic effects of concentrations of 0.1 muM of digitoxin and its cleavage products digitoxigenin-bis-digitoxoside, digitoxigenin-mono-digitoxoside and digitoxigenin in the isolated perfused hearts of guinea-pigs. 2 Digitoxin produced the greatest inotropic responses in this series, while the sequence of cleavage products produced progressively smaller responses. 3 The uptake of digitoxin was significantly higher than that of the three metabolites, and the uptake of metabolites became progressively less with cleavage. The highest binding in each case was found in the microsomal fraction. 4 The uptake of all four digitaloids was reduced when the potassium in the perfusion medium was increased.", "contents": "The uptake and subcellular distribution of radio-labelled metabolites of digitoxin in the guinea-pig isolated perfused heart. 1 Comparisons were made of the uptake and inotropic effects of concentrations of 0.1 muM of digitoxin and its cleavage products digitoxigenin-bis-digitoxoside, digitoxigenin-mono-digitoxoside and digitoxigenin in the isolated perfused hearts of guinea-pigs. 2 Digitoxin produced the greatest inotropic responses in this series, while the sequence of cleavage products produced progressively smaller responses. 3 The uptake of digitoxin was significantly higher than that of the three metabolites, and the uptake of metabolites became progressively less with cleavage. The highest binding in each case was found in the microsomal fraction. 4 The uptake of all four digitaloids was reduced when the potassium in the perfusion medium was increased."} {"id": "PMID:1260225", "title": "Uptake of 5-hydroxytryptamine in different parts of the brain of the rabbit after intraventricular injection.", "content": "1 The uptake of 5-hydroxytryptamine (5-HT) was investigated in different areas of the rabbit brain (anterior hypothalamus, the raphe, the region of the substantia nigra, several cortical areas and the medulla oblongata) after intraventricular injection in pargyline pretreated animals by the formaldehyde-induced histochemical fluorescence method. 2 The distribution of fluorescence showed that the uptake of 5-HT, after circulation in the cerebrospinal fluid, caused a general increase in intensity of green yellow to yellow background fluorescence. There was an increased fluorescence in the nerve terminals, but no uptake occurred either in the cell bodies of neurones or in the glial cells.", "contents": "Uptake of 5-hydroxytryptamine in different parts of the brain of the rabbit after intraventricular injection. 1 The uptake of 5-hydroxytryptamine (5-HT) was investigated in different areas of the rabbit brain (anterior hypothalamus, the raphe, the region of the substantia nigra, several cortical areas and the medulla oblongata) after intraventricular injection in pargyline pretreated animals by the formaldehyde-induced histochemical fluorescence method. 2 The distribution of fluorescence showed that the uptake of 5-HT, after circulation in the cerebrospinal fluid, caused a general increase in intensity of green yellow to yellow background fluorescence. There was an increased fluorescence in the nerve terminals, but no uptake occurred either in the cell bodies of neurones or in the glial cells."} {"id": "PMID:1260226", "title": "The relationship between calcium and increased sensitivity of rabbit aortae four hours after reserpine.", "content": "1 Four hours after reserpine, rabbit aortic strips were supersensitive to acetylcholine, isoprenaline and noradrenaline. The threshold concentration of the drugs necessary to induce a response was less and the maximum tension developed by the tissues was greater than in control strips. 2 Reserpine-treatment potentiated the contractile responses to CaCl2. 3 Reserpine-treatment resulted in an increase in calcium uptake and an increase in the slow component of 45Ca2+ efflux. 4 After resperine-treatment, the rate of relaxation from a potassium-induced contraction was decreased. 5 It is concluded that reserpine-induced supersensitivity is related to an enhanced ability of the tissue to retain and utilize calcium.", "contents": "The relationship between calcium and increased sensitivity of rabbit aortae four hours after reserpine. 1 Four hours after reserpine, rabbit aortic strips were supersensitive to acetylcholine, isoprenaline and noradrenaline. The threshold concentration of the drugs necessary to induce a response was less and the maximum tension developed by the tissues was greater than in control strips. 2 Reserpine-treatment potentiated the contractile responses to CaCl2. 3 Reserpine-treatment resulted in an increase in calcium uptake and an increase in the slow component of 45Ca2+ efflux. 4 After resperine-treatment, the rate of relaxation from a potassium-induced contraction was decreased. 5 It is concluded that reserpine-induced supersensitivity is related to an enhanced ability of the tissue to retain and utilize calcium."} {"id": "PMID:1260227", "title": "Prostaglandin production by rabbit isolated jejunum and its relationship to the inherent tone of the preparation.", "content": "1 Pieces of rabbit jejunum were bathed in Krebs solution at 37 degrees C in an isolated organ bath bubbled with O2 and 5% CO2. The bathing fluid was collected regularly and assayed for prostaglandins. 2 The preparations maintained a continuous sub-maximal muscle contraction, referred to as inherent 'tone'. Prostaglandins E2 and F2alpha were continuously generated by the intestine and released into the bathing fluid. The amounts released first declined over 2 h and then steadily increased. The release was also greater after 48 h storage in the refrigerator and after mechanical damage. 3 There was no change in prostaglandin release when the rabbit jejunum was contractd by acetylcholine or physostigmine or relaxed by adrenaline, hyoscine, papaverine, dinitrophenol, or calcium-free Krebs solution. 4 Addition to the bathing fluid of the prostaglandin precursor, arachidonic acid, did not increase the release of prostaglandins although it contracted the tissue. Thus, output of prostaglandins from the tissue was not limited by substrate concentration but more probably by the capacity of the prostaglandin synthetase. 5 Prostaglandin output was decreased by bubbling the bathing fluid with N2 rather than O2; at the same time the preparation relaxed. 6 Aspirin-like drugs such as indomethacin also decreased or abolished prostaglandin formation and this, too, was accompanied by loss of tone of the isolated preparation. 7 Pieces of rabbit jejunum stored in Krebs solution containing indomethacin initially released little or no prostaglandin into the bathing fluid. However, prostaglandin release increased with repeated washing of the preparation. 8 The results suggest that intra-mural prostaglandin production contributes to the inherent tone of the rabbit jejunum, that trauma increases prostaglandin production and that the inhibitory effects of anoxia are linked with the lack of prostaglandin production and activity. The relevance of these findings to intestinal activity in vivo is discussed.", "contents": "Prostaglandin production by rabbit isolated jejunum and its relationship to the inherent tone of the preparation. 1 Pieces of rabbit jejunum were bathed in Krebs solution at 37 degrees C in an isolated organ bath bubbled with O2 and 5% CO2. The bathing fluid was collected regularly and assayed for prostaglandins. 2 The preparations maintained a continuous sub-maximal muscle contraction, referred to as inherent 'tone'. Prostaglandins E2 and F2alpha were continuously generated by the intestine and released into the bathing fluid. The amounts released first declined over 2 h and then steadily increased. The release was also greater after 48 h storage in the refrigerator and after mechanical damage. 3 There was no change in prostaglandin release when the rabbit jejunum was contractd by acetylcholine or physostigmine or relaxed by adrenaline, hyoscine, papaverine, dinitrophenol, or calcium-free Krebs solution. 4 Addition to the bathing fluid of the prostaglandin precursor, arachidonic acid, did not increase the release of prostaglandins although it contracted the tissue. Thus, output of prostaglandins from the tissue was not limited by substrate concentration but more probably by the capacity of the prostaglandin synthetase. 5 Prostaglandin output was decreased by bubbling the bathing fluid with N2 rather than O2; at the same time the preparation relaxed. 6 Aspirin-like drugs such as indomethacin also decreased or abolished prostaglandin formation and this, too, was accompanied by loss of tone of the isolated preparation. 7 Pieces of rabbit jejunum stored in Krebs solution containing indomethacin initially released little or no prostaglandin into the bathing fluid. However, prostaglandin release increased with repeated washing of the preparation. 8 The results suggest that intra-mural prostaglandin production contributes to the inherent tone of the rabbit jejunum, that trauma increases prostaglandin production and that the inhibitory effects of anoxia are linked with the lack of prostaglandin production and activity. The relevance of these findings to intestinal activity in vivo is discussed."} {"id": "PMID:1260228", "title": "The effects of dimercaptosuccinic acid on the excretion and distribution of mercury in rats and mice treated with mercuric chloride and methylmercury chloride.", "content": "1 All five rats in a group survived if dimercaptosuccinic acid (DMSA), a water soluble derivative of 2,3-dimercaptopropanol (BAL), was given in doses of 10-40 mg/kg intraperitoneally 30 min, 4 and 24 h after administration of 2.4 mg/kg Hg as HgCl2, whereas three out of a group of five died if DMSA was not given. DMSA 20 mg/kg increased urinary excretion and decreased the body burden significantly more than 10 mg/kg DMSA, but further doubling of the dose had only marginal effects. 2 DMSA was able to reduce body burden and increase urinary excretion of Hg when intraperitoneal treatment started eight days after the subcutaneous administration of HgCl2. 3 DMSA was effective in decreasing body burden and the brain concentration of Hg in rats dosed orally with methylmercury (MeHgCl) when intraperitoneal treatment started with 40 mg/kg DMSA 24 h after Hg. Increase in the urinary excretion of mercury was responsible for the decrease in body burden. 4 DMSA was effective when given in the drinking water of rats or mice both against inorganic Hg and MeHgCl. In mice treated intraperitoneally with MeHgCl, DMSA 19.5 mug/ml in the drinking water caused a significant decrease in the body burden and increase in the excretion of Hg. 5 DMSA was about four times more efficient than D-penicillamine in decreasing the body burden of Hg. As their toxicity is in the same range, the higher efficiency of DMSA offers a larger margin of safety for the mobilization of Hg.", "contents": "The effects of dimercaptosuccinic acid on the excretion and distribution of mercury in rats and mice treated with mercuric chloride and methylmercury chloride. 1 All five rats in a group survived if dimercaptosuccinic acid (DMSA), a water soluble derivative of 2,3-dimercaptopropanol (BAL), was given in doses of 10-40 mg/kg intraperitoneally 30 min, 4 and 24 h after administration of 2.4 mg/kg Hg as HgCl2, whereas three out of a group of five died if DMSA was not given. DMSA 20 mg/kg increased urinary excretion and decreased the body burden significantly more than 10 mg/kg DMSA, but further doubling of the dose had only marginal effects. 2 DMSA was able to reduce body burden and increase urinary excretion of Hg when intraperitoneal treatment started eight days after the subcutaneous administration of HgCl2. 3 DMSA was effective in decreasing body burden and the brain concentration of Hg in rats dosed orally with methylmercury (MeHgCl) when intraperitoneal treatment started with 40 mg/kg DMSA 24 h after Hg. Increase in the urinary excretion of mercury was responsible for the decrease in body burden. 4 DMSA was effective when given in the drinking water of rats or mice both against inorganic Hg and MeHgCl. In mice treated intraperitoneally with MeHgCl, DMSA 19.5 mug/ml in the drinking water caused a significant decrease in the body burden and increase in the excretion of Hg. 5 DMSA was about four times more efficient than D-penicillamine in decreasing the body burden of Hg. As their toxicity is in the same range, the higher efficiency of DMSA offers a larger margin of safety for the mobilization of Hg."} {"id": "PMID:1260230", "title": "Where do psychiatrists come from? The influence of United Kingdom medical schools on the choice of psychiatry as a career.", "content": "The medical schools of origin of 531 psychiatrists who had qualified in the U.K. in the period of 1961-1970 were ascertained. Psychiatrists were for the purpose of the study operationally defined as those who had taken the Royal College of Psychiatrists' Membership examinations since its inception. There were large discrepancies, as much as five-fold, between different medical schools, and no ready explanation is forthcoming. There were also discrepancies in the proportion of women graduates opting for psychiatry.", "contents": "Where do psychiatrists come from? The influence of United Kingdom medical schools on the choice of psychiatry as a career. The medical schools of origin of 531 psychiatrists who had qualified in the U.K. in the period of 1961-1970 were ascertained. Psychiatrists were for the purpose of the study operationally defined as those who had taken the Royal College of Psychiatrists' Membership examinations since its inception. There were large discrepancies, as much as five-fold, between different medical schools, and no ready explanation is forthcoming. There were also discrepancies in the proportion of women graduates opting for psychiatry."} {"id": "PMID:1260229", "title": "Stereoselective binding in cardiac tissue of the enatiomers of benzetimide, and antimuscarinic drug.", "content": "1 Benzetimide, possessing two stable enantiomers, dexetimide and levetimide, has been investigated in guinea-pig atria with respect to its atropine-like action and its tissue distribution. 2 The antagonistic potency of dexetimide was found to be over 6000 times higher than that of levetimide, the pA2 values being 9.82 and 6.0 respectively. 3 The tissue accumulation was investigated for both isomers in the concentration range from 1.5 X 10(-9) M to 10(-6) M yielding tissue to medium ratios (T/M) of between approximately 50 and 10. The highest values were found for the lowest concentrations. At any concentration investigated, dexetimide exhibited a higher uptake than the levoisomer. 4 The rate of uptake and washout of dexetimide was extremely slow, that of levetimide being considerably faster at equimolar concentrations. The same pattern held true for the onset and decline of the antagonistic action. 5 The high accumulation was found to be almost entirely due to unspecific binding. Even in the case of dexetimide the relative size of the receptor compartment could not be determined. The unspecific binding sites displayed a certain stereoselectivity but to a much lesser extent than the specific receptor binding sites.", "contents": "Stereoselective binding in cardiac tissue of the enatiomers of benzetimide, and antimuscarinic drug. 1 Benzetimide, possessing two stable enantiomers, dexetimide and levetimide, has been investigated in guinea-pig atria with respect to its atropine-like action and its tissue distribution. 2 The antagonistic potency of dexetimide was found to be over 6000 times higher than that of levetimide, the pA2 values being 9.82 and 6.0 respectively. 3 The tissue accumulation was investigated for both isomers in the concentration range from 1.5 X 10(-9) M to 10(-6) M yielding tissue to medium ratios (T/M) of between approximately 50 and 10. The highest values were found for the lowest concentrations. At any concentration investigated, dexetimide exhibited a higher uptake than the levoisomer. 4 The rate of uptake and washout of dexetimide was extremely slow, that of levetimide being considerably faster at equimolar concentrations. The same pattern held true for the onset and decline of the antagonistic action. 5 The high accumulation was found to be almost entirely due to unspecific binding. Even in the case of dexetimide the relative size of the receptor compartment could not be determined. The unspecific binding sites displayed a certain stereoselectivity but to a much lesser extent than the specific receptor binding sites."} {"id": "PMID:1260231", "title": "The cohesiveness of alcoholism-complicated marriages and its influence on treatment outcome.", "content": "One-hundred husbands, diagnosed as suffering from alcoholism, and their wives, were followed up twelve months after initial consultation and assessment. Follow-up information was complete in 89 cases. On the basis of both husband and wife accounts of the husband's drinking behaviour during the follow-up period, and their assessment of the drinking problem at twelve-months follow-up, 28 were classified as having a 'good' outcome and 29 as having a 'bad' outcome. In the remaining 32 cases outcome was considered 'equivocal'. A composite measure of marital cohesion was predictive of twelve-month outcome classification, cohesive marriages being significantly more likely to have a good outcome. The measure of marital cohesion was based upon husband and wife reports of mutual affection and of husband involvement in family tasks, favourable spouse perceptions and meta-perceptions, and optimism about the future of the marriage. Composite measures of dominance balance within the marriage were not predictive of outcome. Husband's job status, husband's self-esteem, and wife's reported hardship were not independent of marital cohesion, and were themseleves predictive of twelve-months outcome. When these variables were partially controlled it was found that marital cohesion remained predictive for husbands with relatively low status jobs and husbands with relatively low levels of self-esteem. It is an over-simplification to state that either the marriage, the spouse, or the severity of the patient's condition is alone the cause of variation in outcome. It is possible to integrate these findings with those of other studies on the influence of family variables on the outcom of conditions other than alcoholism. Together these studies suggest a general hypothesis linking a breakdown in the cohesiveness, or mutual rewardingness, of family relationships and unfavourable outcomes following treatment or consultation for psychological disorder.", "contents": "The cohesiveness of alcoholism-complicated marriages and its influence on treatment outcome. One-hundred husbands, diagnosed as suffering from alcoholism, and their wives, were followed up twelve months after initial consultation and assessment. Follow-up information was complete in 89 cases. On the basis of both husband and wife accounts of the husband's drinking behaviour during the follow-up period, and their assessment of the drinking problem at twelve-months follow-up, 28 were classified as having a 'good' outcome and 29 as having a 'bad' outcome. In the remaining 32 cases outcome was considered 'equivocal'. A composite measure of marital cohesion was predictive of twelve-month outcome classification, cohesive marriages being significantly more likely to have a good outcome. The measure of marital cohesion was based upon husband and wife reports of mutual affection and of husband involvement in family tasks, favourable spouse perceptions and meta-perceptions, and optimism about the future of the marriage. Composite measures of dominance balance within the marriage were not predictive of outcome. Husband's job status, husband's self-esteem, and wife's reported hardship were not independent of marital cohesion, and were themseleves predictive of twelve-months outcome. When these variables were partially controlled it was found that marital cohesion remained predictive for husbands with relatively low status jobs and husbands with relatively low levels of self-esteem. It is an over-simplification to state that either the marriage, the spouse, or the severity of the patient's condition is alone the cause of variation in outcome. It is possible to integrate these findings with those of other studies on the influence of family variables on the outcom of conditions other than alcoholism. Together these studies suggest a general hypothesis linking a breakdown in the cohesiveness, or mutual rewardingness, of family relationships and unfavourable outcomes following treatment or consultation for psychological disorder."} {"id": "PMID:1260232", "title": "Certificated incapacity and unemployment in alcoholics.", "content": "Seventy-three male alcoholics permitted information to be obtained from official sources about time recorded as lost from work in receipt of sickness or unemployment benefits and about their weekly state insurance contributions. The average yearly time loss was 121-7 working days per person, comprising an average yearly loss through sickness of 86-1 and through unemployment of 35-6 working days respectively. By contrast the recorded national sickness loss for men in a comparable twelve months period averaged 15-9 working days per person. Thirteen alcoholics showed over five years, prolonged deficiency in work attendance. State benefits to the subjects, over twelve months during the early 1970s, totalled pounds 18,434.80. Diagnoses on their medical certificates underestimated incapacity from alcoholism.", "contents": "Certificated incapacity and unemployment in alcoholics. Seventy-three male alcoholics permitted information to be obtained from official sources about time recorded as lost from work in receipt of sickness or unemployment benefits and about their weekly state insurance contributions. The average yearly time loss was 121-7 working days per person, comprising an average yearly loss through sickness of 86-1 and through unemployment of 35-6 working days respectively. By contrast the recorded national sickness loss for men in a comparable twelve months period averaged 15-9 working days per person. Thirteen alcoholics showed over five years, prolonged deficiency in work attendance. State benefits to the subjects, over twelve months during the early 1970s, totalled pounds 18,434.80. Diagnoses on their medical certificates underestimated incapacity from alcoholism."} {"id": "PMID:1260233", "title": "Deliberate self-harm: a follow-up study of 279 patients.", "content": "Two-hundred-and-seventy-nine patients (103 men, 176 women) were followed-up 1-2 years after an act of non-fatal deliberate self-harm. Of 155 patients offered a psychiatric out-patient appointment at the time, only 68 completed the treatment. A further act of deliberate self-harm was committed by 26 men and 41 women within twelve months. The factors most highly associated with repetition were previous psychiatric treatment, a previous act of deliberate self-harm, and a criminal record. These factors held good for a separate series of patients. Significantly more repeaters received prolonged psychiatric care after the initial episode of deliberate self-harm. The implications of these findings for the clinical management of such patients are discussed.", "contents": "Deliberate self-harm: a follow-up study of 279 patients. Two-hundred-and-seventy-nine patients (103 men, 176 women) were followed-up 1-2 years after an act of non-fatal deliberate self-harm. Of 155 patients offered a psychiatric out-patient appointment at the time, only 68 completed the treatment. A further act of deliberate self-harm was committed by 26 men and 41 women within twelve months. The factors most highly associated with repetition were previous psychiatric treatment, a previous act of deliberate self-harm, and a criminal record. These factors held good for a separate series of patients. Significantly more repeaters received prolonged psychiatric care after the initial episode of deliberate self-harm. The implications of these findings for the clinical management of such patients are discussed."} {"id": "PMID:1260234", "title": "Temporal stability of symptom patterns in depression.", "content": "Temporal stability of symptom patterns was examined in 33 depressives studied initially at the height of illness and again some months later in a relapse following earlier recovery. Relapse symptoms were significantly less severe at the time of rating, and initial and relapse severity were not significantly related. Neverthless there were significant correlations between initial and relapse scores on two factors orthogonal to severity. One of these reflected symptom patterns important to the endogenous-neurotic distinction, the other a contrast between depression and anxiety. These findings indicate some consistency in symptom patterns in successive episodes of depression, and thereby support the value of clinical classifications depending on symptom patterns.", "contents": "Temporal stability of symptom patterns in depression. Temporal stability of symptom patterns was examined in 33 depressives studied initially at the height of illness and again some months later in a relapse following earlier recovery. Relapse symptoms were significantly less severe at the time of rating, and initial and relapse severity were not significantly related. Neverthless there were significant correlations between initial and relapse scores on two factors orthogonal to severity. One of these reflected symptom patterns important to the endogenous-neurotic distinction, the other a contrast between depression and anxiety. These findings indicate some consistency in symptom patterns in successive episodes of depression, and thereby support the value of clinical classifications depending on symptom patterns."} {"id": "PMID:1260235", "title": "Physiological dependence on, and symptoms of withdrawal from, chlormethiazole.", "content": "The uses of chlormethiazole (Heminevrin) are briefly mentioned. Differing views of its potential for producing dependence are discussed. The consensus opinion is taken to be that a risk of psychological dependence does exist, but only one case has appeared in the medical literature to date of physiological dependence on chlormethiazole, with withdrawal symptoms. This case is re-examined. A second case is described in which the features of increasing dosage and withdrawal were followed by confusion, disorientation, delusions, hallucinations and muscular spasm and coarse jerking. This is taken as confirmation of the potential of chlormethiazole to produce physiological dependence. Some personal opinions of the author regarding indications for use and incidence of abuse are briefly mentioned.", "contents": "Physiological dependence on, and symptoms of withdrawal from, chlormethiazole. The uses of chlormethiazole (Heminevrin) are briefly mentioned. Differing views of its potential for producing dependence are discussed. The consensus opinion is taken to be that a risk of psychological dependence does exist, but only one case has appeared in the medical literature to date of physiological dependence on chlormethiazole, with withdrawal symptoms. This case is re-examined. A second case is described in which the features of increasing dosage and withdrawal were followed by confusion, disorientation, delusions, hallucinations and muscular spasm and coarse jerking. This is taken as confirmation of the potential of chlormethiazole to produce physiological dependence. Some personal opinions of the author regarding indications for use and incidence of abuse are briefly mentioned."} {"id": "PMID:1260236", "title": "Plasma concentrations of protriptyline and clinical effects in depressed women.", "content": "We studied the relationship between side effects, clinical outcome and the drug plasma levels in 28 female depressed patients treated with protriptyline. After 3 1/2 weeks treatment, patients with plasma levels within a median range (630 to 900 nmol/l) showed better responses to the drug than patients with plasma levels outside this range. There were no statistically signficant correlations between plasma levels and side effect scores or 'corrected' side effect scores (scores after subtracting pretreatment values) for the group at any time after starting the treatment. But we found positive correlations between plasma levels and 'corrected' side effect scores for the neurotic subgroup after 14 and 21 days of treatment. Other correlations between plasma levels and side effect scores were non-significant.", "contents": "Plasma concentrations of protriptyline and clinical effects in depressed women. We studied the relationship between side effects, clinical outcome and the drug plasma levels in 28 female depressed patients treated with protriptyline. After 3 1/2 weeks treatment, patients with plasma levels within a median range (630 to 900 nmol/l) showed better responses to the drug than patients with plasma levels outside this range. There were no statistically signficant correlations between plasma levels and side effect scores or 'corrected' side effect scores (scores after subtracting pretreatment values) for the group at any time after starting the treatment. But we found positive correlations between plasma levels and 'corrected' side effect scores for the neurotic subgroup after 14 and 21 days of treatment. Other correlations between plasma levels and side effect scores were non-significant."} {"id": "PMID:1260237", "title": "Childhood separation experiences and psycho-social status in primiparous women: preliminary findings.", "content": "In a group of British-born primiparous women, admission of a separation experience from parents in childhood was found to be associated with unmarried status, teenage pregnancy, having had psychiatric treatment, housing problems and a high score on a 'Malaise' inventory. Within the separated group the unmarried and teenage status were associated only with separations occurring in the context of a disrupted childhood, but were not related to the age of the separations. The Malaise score, however, was raised both for disrupted separations and for those occurring below the age of 5. It is noted that the factors associated with the separation in the mothers are those which have been found to be more common in the mothers of children with behaviour disorders.", "contents": "Childhood separation experiences and psycho-social status in primiparous women: preliminary findings. In a group of British-born primiparous women, admission of a separation experience from parents in childhood was found to be associated with unmarried status, teenage pregnancy, having had psychiatric treatment, housing problems and a high score on a 'Malaise' inventory. Within the separated group the unmarried and teenage status were associated only with separations occurring in the context of a disrupted childhood, but were not related to the age of the separations. The Malaise score, however, was raised both for disrupted separations and for those occurring below the age of 5. It is noted that the factors associated with the separation in the mothers are those which have been found to be more common in the mothers of children with behaviour disorders."} {"id": "PMID:1260238", "title": "Multivariate analysis: data reduction and treatment evaluation.", "content": "In a recent article, Everitt (1975) discussed several problems with multivariate techniques. However, two useful applications of multivariate techniques were not covered. The present paper describes the use of factor analysis to reduce a large array of outcome variables to a statistically manageable number, and multivariate analysis of variance to determine the relative effectiveness of several treatment regimes where a single outcome variable cannot be specified. It is concluded that the advantages of a multivariate approach out-weigh the disadvantages, provided the researcher is careful in interpreting and reporting his results.", "contents": "Multivariate analysis: data reduction and treatment evaluation. In a recent article, Everitt (1975) discussed several problems with multivariate techniques. However, two useful applications of multivariate techniques were not covered. The present paper describes the use of factor analysis to reduce a large array of outcome variables to a statistically manageable number, and multivariate analysis of variance to determine the relative effectiveness of several treatment regimes where a single outcome variable cannot be specified. It is concluded that the advantages of a multivariate approach out-weigh the disadvantages, provided the researcher is careful in interpreting and reporting his results."} {"id": "PMID:1260239", "title": "Responsiveness of delinquents and non-delinquents to social reinforcement.", "content": "A series of six experiments, involving 198 subjects, examined the hypothesis that delinquents are less responsive than non-delinquents to social reinforcement and punishment. The hypothesis received support (a) using two different experimental techniques, one in which the subjects' judgements of autokinetic movement were modified and one using the Taffel (1955) verbal conditioning paradigm; (b) with the female adult administering the reinforcement and with a peer; (c) when the contingent social cues were rewarding (Good or Fine) and when they were punishing ('No'). The hypothesis was not supported when the verbal reinforcement was varied. Control studies using no reinforcement and money reinforcement indicated that the social reinforcement did indeed have a specific reinforcement effect and that delinquents did not show a general learning deficiency.", "contents": "Responsiveness of delinquents and non-delinquents to social reinforcement. A series of six experiments, involving 198 subjects, examined the hypothesis that delinquents are less responsive than non-delinquents to social reinforcement and punishment. The hypothesis received support (a) using two different experimental techniques, one in which the subjects' judgements of autokinetic movement were modified and one using the Taffel (1955) verbal conditioning paradigm; (b) with the female adult administering the reinforcement and with a peer; (c) when the contingent social cues were rewarding (Good or Fine) and when they were punishing ('No'). The hypothesis was not supported when the verbal reinforcement was varied. Control studies using no reinforcement and money reinforcement indicated that the social reinforcement did indeed have a specific reinforcement effect and that delinquents did not show a general learning deficiency."} {"id": "PMID:1260240", "title": "Language behaviour in acute and chronic schizophrenia.", "content": "A predicition made by Broen (1968) regarding the performance of acute and chronic non-paranoid schizophrenics on measures of dominant verbal response bias was tested in a group of 40 hospitalized schizophrenic patients. A subgroup of 10 chronic patients were found to show an abnormal dominant response bias on two different language tasks and on one task showed a bias significantly greater than that shown by a group of 10 acute patients matched on verbal IQ and rated symptomatology. A correlational analysis of the bias scores of the total sample in relation to three indices of chronicity also showed a trend in the predicted direction of a greater dominant response bias with increasing chronicity. The data are consistent with Broen's (1968) theory of dominant response bias as a learned defence against aversive response interference in acute schizophrenia.", "contents": "Language behaviour in acute and chronic schizophrenia. A predicition made by Broen (1968) regarding the performance of acute and chronic non-paranoid schizophrenics on measures of dominant verbal response bias was tested in a group of 40 hospitalized schizophrenic patients. A subgroup of 10 chronic patients were found to show an abnormal dominant response bias on two different language tasks and on one task showed a bias significantly greater than that shown by a group of 10 acute patients matched on verbal IQ and rated symptomatology. A correlational analysis of the bias scores of the total sample in relation to three indices of chronicity also showed a trend in the predicted direction of a greater dominant response bias with increasing chronicity. The data are consistent with Broen's (1968) theory of dominant response bias as a learned defence against aversive response interference in acute schizophrenia."} {"id": "PMID:1260241", "title": "Relationship between conceptual judgements and stimulus dimensions among schizophrenics and normals.", "content": "Eighteen paranoid schizophrenics, 18 non-paranoid schizophrenics and 18 normal subjects were shown a set of 36 schematic drawings of human faces. The faces varied along four dimensions: nose length, chin length, distance between eyes, and forehead height. Subjects were asked to rate each face as either 'intelligent' or 'unintelligent' and then as either 'contented' or 'discontented'. The paranoid schizophrenics were less systematic than both the normals and non-paranoid schizophrenics in their use of the stimulus dimensions in the judgements, the latter two groups not significantly differing in this respect. It was also found that there were significant differences among the groups regarding the average importance given to the different physical features, the profiles for the two schizophrenic groups being flatter than that of the non-schizophrenics. The results suggested there were two aspects of consistency in dimension utilization involved in the overall group differences-between-subject and within-subject consistency. The paranoid schizophrenics displayed low within-subject consistency, the non-paranoid schizophrenics displayed a high within-subject consistency but low between-subject consistency (i.e. an idiosyncratic weighting of dimensions in their judgements), and the non-schizophrenics displayed high within- and between-subject consistency.", "contents": "Relationship between conceptual judgements and stimulus dimensions among schizophrenics and normals. Eighteen paranoid schizophrenics, 18 non-paranoid schizophrenics and 18 normal subjects were shown a set of 36 schematic drawings of human faces. The faces varied along four dimensions: nose length, chin length, distance between eyes, and forehead height. Subjects were asked to rate each face as either 'intelligent' or 'unintelligent' and then as either 'contented' or 'discontented'. The paranoid schizophrenics were less systematic than both the normals and non-paranoid schizophrenics in their use of the stimulus dimensions in the judgements, the latter two groups not significantly differing in this respect. It was also found that there were significant differences among the groups regarding the average importance given to the different physical features, the profiles for the two schizophrenic groups being flatter than that of the non-schizophrenics. The results suggested there were two aspects of consistency in dimension utilization involved in the overall group differences-between-subject and within-subject consistency. The paranoid schizophrenics displayed low within-subject consistency, the non-paranoid schizophrenics displayed a high within-subject consistency but low between-subject consistency (i.e. an idiosyncratic weighting of dimensions in their judgements), and the non-schizophrenics displayed high within- and between-subject consistency."} {"id": "PMID:1260242", "title": "Temporal lobe swelling: a common treatable complication of head injury.", "content": "Four cases are described of focal contusion and swelling of the temporal lobe after head injury, giving rise to acute cerebral compression. The clinical features, pathology and treatment of this condition are discussed. It is suggested that this occurrence may be a common treatable complication of closed head injuries which may easily be overlooked, with fatal results, if exploratory cranial surgery is undertaken without preliminary cerebral angiography.", "contents": "Temporal lobe swelling: a common treatable complication of head injury. Four cases are described of focal contusion and swelling of the temporal lobe after head injury, giving rise to acute cerebral compression. The clinical features, pathology and treatment of this condition are discussed. It is suggested that this occurrence may be a common treatable complication of closed head injuries which may easily be overlooked, with fatal results, if exploratory cranial surgery is undertaken without preliminary cerebral angiography."} {"id": "PMID:1260243", "title": "Primary malignant tumours of the thyroid: the relationship between histological classification and clinical behaviour.", "content": "One hundred and seventy-nine primary malignant tumours of the thyroid seen at The London Hospital between 1945 and 1972 were classified by the system of Woolner et al. (1961) and Hazard (1964). The distinct pathological and clinical features of the differentiated primary carcinomas and the similarities and differences between malignant lymphoma and anaplastic carcinoma were confirmed. This study showed the 'benign' behaviour of more than half the 'differentiated' papillary and follicular carcinomas when treated by thyroid lobectomy and the very malignant nature of anaplastic carcinomas and lymphomas whatever their treatment. The behaviour of medullary carcinoma was closer to that of the other differentiated tumours than to the undifferentiated varieties. Our patients were not thought to have been exposed to known goitrogens or previous thyroid irradiation.", "contents": "Primary malignant tumours of the thyroid: the relationship between histological classification and clinical behaviour. One hundred and seventy-nine primary malignant tumours of the thyroid seen at The London Hospital between 1945 and 1972 were classified by the system of Woolner et al. (1961) and Hazard (1964). The distinct pathological and clinical features of the differentiated primary carcinomas and the similarities and differences between malignant lymphoma and anaplastic carcinoma were confirmed. This study showed the 'benign' behaviour of more than half the 'differentiated' papillary and follicular carcinomas when treated by thyroid lobectomy and the very malignant nature of anaplastic carcinomas and lymphomas whatever their treatment. The behaviour of medullary carcinoma was closer to that of the other differentiated tumours than to the undifferentiated varieties. Our patients were not thought to have been exposed to known goitrogens or previous thyroid irradiation."} {"id": "PMID:1260244", "title": "Paraganglionomas in the neck.", "content": "Three paraganglionomas in the neck investigated by angiography are presented. The value of angiography in these tumours is stressed, and one case showed distinctive radiological features hitherto undescribed which probably constitute a basis for the definitive preoperative diagnosis of malignant lesions.", "contents": "Paraganglionomas in the neck. Three paraganglionomas in the neck investigated by angiography are presented. The value of angiography in these tumours is stressed, and one case showed distinctive radiological features hitherto undescribed which probably constitute a basis for the definitive preoperative diagnosis of malignant lesions."} {"id": "PMID:1260245", "title": "Experimental carotid-basilar bypass.", "content": "A procedure for anastomosing the carotid to the vertebrobasilar circulation in the dog is described. A total of 20 experiments (10 acute and 10 chronic) were performed on dogs. The grafted vessel was found to be patent in 2 out of 4 dogs at 3 months after operation. The flow through the grafts, recorded by electromagnetic flowmeter, was 5-9 ml/min.", "contents": "Experimental carotid-basilar bypass. A procedure for anastomosing the carotid to the vertebrobasilar circulation in the dog is described. A total of 20 experiments (10 acute and 10 chronic) were performed on dogs. The grafted vessel was found to be patent in 2 out of 4 dogs at 3 months after operation. The flow through the grafts, recorded by electromagnetic flowmeter, was 5-9 ml/min."} {"id": "PMID:1260246", "title": "Grafting of the major veins: the value of anti-thrombotic drugs to maintain patency.", "content": "The value of anti-thrombotic drugs to maintain the patency of grafts into the central venous system is described. The infrarenal portion of the inferior vena cava in mongrel dogs was used as the test bed. Two autologous graft materials were used: first, the tissue reaction to implanted silicone rubber, and, secondly, free peritoneum. Phenylbutazone was the drug administered to inhibit the aggregation of platelets at the bloodgraft interface. The low patency rate of the control group of animals conformed with previous experimental studies. The patency of grafts in the phenylbutazone-treated animals (up to 92%) was predictable after studying the in vitro behaviour of their platelets preoperatively.", "contents": "Grafting of the major veins: the value of anti-thrombotic drugs to maintain patency. The value of anti-thrombotic drugs to maintain the patency of grafts into the central venous system is described. The infrarenal portion of the inferior vena cava in mongrel dogs was used as the test bed. Two autologous graft materials were used: first, the tissue reaction to implanted silicone rubber, and, secondly, free peritoneum. Phenylbutazone was the drug administered to inhibit the aggregation of platelets at the bloodgraft interface. The low patency rate of the control group of animals conformed with previous experimental studies. The patency of grafts in the phenylbutazone-treated animals (up to 92%) was predictable after studying the in vitro behaviour of their platelets preoperatively."} {"id": "PMID:1260247", "title": "Peripheral aneurysms in Beh\u0109et's disease.", "content": "Two patients with Beh\u0109et's disease are reported, both of whom had aneurysms of peripheral arteries. In one the aneurysms were multiple. The aneurysm was replaced with a Terylene prosthesis in one patient, and in the other an autogenous vein bypass was used. In each case a further aneurysm developed adjacent to the vascular anastomosis. Severe ischaemia of the affected limbs subsequently developed in both patients.", "contents": "Peripheral aneurysms in Beh\u0109et's disease. Two patients with Beh\u0109et's disease are reported, both of whom had aneurysms of peripheral arteries. In one the aneurysms were multiple. The aneurysm was replaced with a Terylene prosthesis in one patient, and in the other an autogenous vein bypass was used. In each case a further aneurysm developed adjacent to the vascular anastomosis. Severe ischaemia of the affected limbs subsequently developed in both patients."} {"id": "PMID:1260248", "title": "Parietal pleurectomy for recurrent pneumothorax.", "content": "One hundred patients with persistent or recurrent pneumothorax treated by parietal pleurectomy are described. There was one known recurrence and no postoperative deaths. Six patients required further surgery for complications. In the uncomplicated cases the average stay in hospital following operation was 11-5 days. Parietal pleurectomy should be regarded as the treatment of choice for patients with recurrent pneumothorax who are fit to undergo surgery.", "contents": "Parietal pleurectomy for recurrent pneumothorax. One hundred patients with persistent or recurrent pneumothorax treated by parietal pleurectomy are described. There was one known recurrence and no postoperative deaths. Six patients required further surgery for complications. In the uncomplicated cases the average stay in hospital following operation was 11-5 days. Parietal pleurectomy should be regarded as the treatment of choice for patients with recurrent pneumothorax who are fit to undergo surgery."} {"id": "PMID:1260249", "title": "Resection and reconstruction for carcinoma of the thoracic oesophagus.", "content": "The technique and results of oesophageal resection through a right thoracotomy and laparotomy with reconstruction utilizing the stomach via a retrosternal route are reported. Forty patients underwent this procedure, with no mortality. The average blood loss during operation was 424 ml, and 72% of this series underwent the operation without blood transfusion. It is believed that this type of one-stage operation for carcinoma of the oesophagus is reasonable from the viewpoint of adequate resection of malignancies, and it can be performed with minimal surgical risk. With experience, perhaps it will become a standard method such as the Billroth I method in gastric surgery.", "contents": "Resection and reconstruction for carcinoma of the thoracic oesophagus. The technique and results of oesophageal resection through a right thoracotomy and laparotomy with reconstruction utilizing the stomach via a retrosternal route are reported. Forty patients underwent this procedure, with no mortality. The average blood loss during operation was 424 ml, and 72% of this series underwent the operation without blood transfusion. It is believed that this type of one-stage operation for carcinoma of the oesophagus is reasonable from the viewpoint of adequate resection of malignancies, and it can be performed with minimal surgical risk. With experience, perhaps it will become a standard method such as the Billroth I method in gastric surgery."} {"id": "PMID:1260250", "title": "Kinin levels in the peripheral venous blood of patients with severe vasomotor dumping before and after revisional surgery.", "content": "The kinin activity in peripheral venous blood was estimated before and after jejunal interposition in 17 patients with severe vasomotor dumpling. In each case the kinin activity was assayed both under fasting conditions and after the oral administration of a liquid hypertonic glucose meal (100 g). No significant difference in the preoperative fasting kinin values was found between patients who were improved of their symptoms (11 cases) as distinct from those who did not derive any benefit from jejunal interposition (6 cases). However, in patients who obtained relief after revisional surgery, the kinin level after glucose administration (56-15 +/- 11-19 ng/ml) was significantly higher (P less than 0-01) than the release obtained in patients who were not improved by surgery (3-65 +/- 2-33 ng/ml). Furthermore, the kinin release was reduced to near normal levels on re-challenge with glucose 3 months after jejunal interposition in patients who were cured or improved of their symptoms.", "contents": "Kinin levels in the peripheral venous blood of patients with severe vasomotor dumping before and after revisional surgery. The kinin activity in peripheral venous blood was estimated before and after jejunal interposition in 17 patients with severe vasomotor dumpling. In each case the kinin activity was assayed both under fasting conditions and after the oral administration of a liquid hypertonic glucose meal (100 g). No significant difference in the preoperative fasting kinin values was found between patients who were improved of their symptoms (11 cases) as distinct from those who did not derive any benefit from jejunal interposition (6 cases). However, in patients who obtained relief after revisional surgery, the kinin level after glucose administration (56-15 +/- 11-19 ng/ml) was significantly higher (P less than 0-01) than the release obtained in patients who were not improved by surgery (3-65 +/- 2-33 ng/ml). Furthermore, the kinin release was reduced to near normal levels on re-challenge with glucose 3 months after jejunal interposition in patients who were cured or improved of their symptoms."} {"id": "PMID:1260251", "title": "Lobar dearterialization in liver trauma.", "content": "Two cases of blunt liver trauma managed by hepatic artery ligation are reported. Lobar dearterialization is a simple and effective method of achieving haemostasis in exsanguinating wounds of the liver. The postoperative management and scope of this procedure are discussed.", "contents": "Lobar dearterialization in liver trauma. Two cases of blunt liver trauma managed by hepatic artery ligation are reported. Lobar dearterialization is a simple and effective method of achieving haemostasis in exsanguinating wounds of the liver. The postoperative management and scope of this procedure are discussed."} {"id": "PMID:1260252", "title": "The clinical presentation of pyogenic liver abscess.", "content": "The high mortality rate from pyogenic liver abscess is contributed to by delay in diagnosis. The widespread availability of radio-isotope liver scanning facilitates diagnosis once a hepatic abscess is suspected. This retrospective study identifies diagnostic features present at the time of admission to hospital in 28 patients who were subsequently found to have a hepatic abscess.", "contents": "The clinical presentation of pyogenic liver abscess. The high mortality rate from pyogenic liver abscess is contributed to by delay in diagnosis. The widespread availability of radio-isotope liver scanning facilitates diagnosis once a hepatic abscess is suspected. This retrospective study identifies diagnostic features present at the time of admission to hospital in 28 patients who were subsequently found to have a hepatic abscess."} {"id": "PMID:1260253", "title": "Syndromes in amoebic liver abscess.", "content": "A series of 137 patients with amoebic liver abscess has been studied. Recognition of clearly defined but diverse clinical syndromes was found to be necessary not only in diagnosis but also in planned surgical management. The majority of patients had the classic syndrome of fever, right abdominal or chest pain, hepatomegaly, hepatic tenderness and radiological abnormalities. Other syndromes of presentation included the silent abscess, acute amoebic colitis, the acute abdomen, the intraabdominal lump, the external sinus, pyrexia of obscure origin, obstructive jaundice and renal, pleuro-pulmonary and cardiac symptoms. The syndromes due to an abscess in different parts of the right lobe and in the left lobe of the liver are to some extent distinct. In spite of the varied modes of presentation of amoebic liver abscess, the key to diagnosis is an understanding of the chronological sequence of the disease and its progression from one syndrome to another. Diagnostic methods of value and the mortality are discussed.", "contents": "Syndromes in amoebic liver abscess. A series of 137 patients with amoebic liver abscess has been studied. Recognition of clearly defined but diverse clinical syndromes was found to be necessary not only in diagnosis but also in planned surgical management. The majority of patients had the classic syndrome of fever, right abdominal or chest pain, hepatomegaly, hepatic tenderness and radiological abnormalities. Other syndromes of presentation included the silent abscess, acute amoebic colitis, the acute abdomen, the intraabdominal lump, the external sinus, pyrexia of obscure origin, obstructive jaundice and renal, pleuro-pulmonary and cardiac symptoms. The syndromes due to an abscess in different parts of the right lobe and in the left lobe of the liver are to some extent distinct. In spite of the varied modes of presentation of amoebic liver abscess, the key to diagnosis is an understanding of the chronological sequence of the disease and its progression from one syndrome to another. Diagnostic methods of value and the mortality are discussed."} {"id": "PMID:1260254", "title": "Blunt pancreatic and pancreaticoduodenal trauma.", "content": "Three cases of pancreatic injury and 1 case of pancreaticoduodenal injury caused by blunt trauma are reported. The literature is reviewed with reference to these cases in respect of incidence, mortality, complications, diagnosis and treatment.", "contents": "Blunt pancreatic and pancreaticoduodenal trauma. Three cases of pancreatic injury and 1 case of pancreaticoduodenal injury caused by blunt trauma are reported. The literature is reviewed with reference to these cases in respect of incidence, mortality, complications, diagnosis and treatment."} {"id": "PMID:1260255", "title": "Septic complications of pancreatitis.", "content": "Over an 11-year period 693 patients with acute pancreatitis and 317 with chronic pancreatitis were seen at the Harbor General Hospital. Review of these cases revealed 9 patients with primary pancreatic lesser sac abscess and 11 with secondary abscess. The appropriate management for pancreatic abscess, whether primary or secondary, is early recognition and drainage; multiple drainage procedures may be necessary. Broad spectrum antibodies appear to be helpful and should be used until cultures indicate more appropriate antibiotic therapy. Successful management involves prolonged hospitalization, but contrary to previous reports the success rate is surprisingly high. Eight out of 9 patients with primary abscess and 8 out of 11 patients with secondary abscess survived.", "contents": "Septic complications of pancreatitis. Over an 11-year period 693 patients with acute pancreatitis and 317 with chronic pancreatitis were seen at the Harbor General Hospital. Review of these cases revealed 9 patients with primary pancreatic lesser sac abscess and 11 with secondary abscess. The appropriate management for pancreatic abscess, whether primary or secondary, is early recognition and drainage; multiple drainage procedures may be necessary. Broad spectrum antibodies appear to be helpful and should be used until cultures indicate more appropriate antibiotic therapy. Successful management involves prolonged hospitalization, but contrary to previous reports the success rate is surprisingly high. Eight out of 9 patients with primary abscess and 8 out of 11 patients with secondary abscess survived."} {"id": "PMID:1260256", "title": "Fistula formation complicating pancreatic abscess.", "content": "Internal fistula formation is a rare complication of pancreatic abscess or pseudocyst; a fairly extensive search of the literature has produced only 47 cases. Common factors in the aetiology, presentation and management are discussed, and a further case is reported which demonstrates many features of this unusual condition.", "contents": "Fistula formation complicating pancreatic abscess. Internal fistula formation is a rare complication of pancreatic abscess or pseudocyst; a fairly extensive search of the literature has produced only 47 cases. Common factors in the aetiology, presentation and management are discussed, and a further case is reported which demonstrates many features of this unusual condition."} {"id": "PMID:1260257", "title": "Carcinoids of the first part of the duodenum.", "content": "Three cases of duodenal carcinoid tumour are described and the histology of this type of tumour is discussed. Two of the patients have been followed up for 8 years. No further complications related to the tumours have been observed.", "contents": "Carcinoids of the first part of the duodenum. Three cases of duodenal carcinoid tumour are described and the histology of this type of tumour is discussed. Two of the patients have been followed up for 8 years. No further complications related to the tumours have been observed."} {"id": "PMID:1260258", "title": "The effect of methionine on colonic wound healing in malnourished rats.", "content": "Recent studies have suggested that the healing of colonic anastomoses is impaired in malnourished subjects. It has been claimed that the healing of skin and abdominal wounds in experimental animals is improved by the administration of the essential amino acid methionine, and in the present study the effects of methionine on colonic wound healing were studied in malnourished rats. Test animals were fed a protein-free diet for 7 weeks before surgery. Methionine-treated animals received the amino acid by subcutaneous injection during the seventh week of protein deprivation and throughout the postoperative period. Anastomoses were made in the left colon, and colonic wound healing was assessed by measurements of the bursting wall tension and collagen content of anastomoses. The results were compared with those of control animals fed a normal rat diet. Protein deprivation for 7 weeks resulted in a 34% reduction in body weight, and a significant reduction in the tensile strength and collagen content of colonic anastomoses was observed. Methionine supplements had no apparent effect on these parameters of wound healing. The concept of single amino acid supplementation in cachetic patients undergoing surgery is an attractive one, but it has yet to be established that methionine supplements alone can alter the course of wound healing in such cases.", "contents": "The effect of methionine on colonic wound healing in malnourished rats. Recent studies have suggested that the healing of colonic anastomoses is impaired in malnourished subjects. It has been claimed that the healing of skin and abdominal wounds in experimental animals is improved by the administration of the essential amino acid methionine, and in the present study the effects of methionine on colonic wound healing were studied in malnourished rats. Test animals were fed a protein-free diet for 7 weeks before surgery. Methionine-treated animals received the amino acid by subcutaneous injection during the seventh week of protein deprivation and throughout the postoperative period. Anastomoses were made in the left colon, and colonic wound healing was assessed by measurements of the bursting wall tension and collagen content of anastomoses. The results were compared with those of control animals fed a normal rat diet. Protein deprivation for 7 weeks resulted in a 34% reduction in body weight, and a significant reduction in the tensile strength and collagen content of colonic anastomoses was observed. Methionine supplements had no apparent effect on these parameters of wound healing. The concept of single amino acid supplementation in cachetic patients undergoing surgery is an attractive one, but it has yet to be established that methionine supplements alone can alter the course of wound healing in such cases."} {"id": "PMID:1260259", "title": "Open pedicle grafts of ileum for the repair of large duodenal defects: an experimental study.", "content": "An experimental study of open pedicle grafts of ileum for the repair of large duodenal defects is presented. All the grafts survived and functioned well. No shrinkage occurred. The results are extremely encouraging for the clinical application of this technique.", "contents": "Open pedicle grafts of ileum for the repair of large duodenal defects: an experimental study. An experimental study of open pedicle grafts of ileum for the repair of large duodenal defects is presented. All the grafts survived and functioned well. No shrinkage occurred. The results are extremely encouraging for the clinical application of this technique."} {"id": "PMID:1260260", "title": "Tension pneumothorax from a perforated gastric ulcer.", "content": "A case of tension pneumothorax from a perforated gastric ulcer is reported and the pathogenesis and management of this rare complication are discussed.", "contents": "Tension pneumothorax from a perforated gastric ulcer. A case of tension pneumothorax from a perforated gastric ulcer is reported and the pathogenesis and management of this rare complication are discussed."} {"id": "PMID:1260261", "title": "An unusual presentation of carcinoma of the rectum.", "content": "The case is described of a middle-aged man whose rectal carcinoma presented with meningitis, due to a fistula into the spinal theca.", "contents": "An unusual presentation of carcinoma of the rectum. The case is described of a middle-aged man whose rectal carcinoma presented with meningitis, due to a fistula into the spinal theca."} {"id": "PMID:1260271", "title": "Cellular immunity to Hodgkin's splenic tissue measured by leucocyte migration inhibition.", "content": "Patients with lymphoreticular malignancy were shown by a leucocyte migration inhibition technique to have cellular immunity to Hodgkin's splenic tissue. Migration was significantly inhibited in 31 out of 55 patients with Hodgkin's lymphoma and 19 out of 39 patients with other types of lymphoma. Inhibition was also shown in only three out of 29 patients with other malignancy, one out of 23 normal volunteers, and one out of 25 patients with non-malignant disease. The splenic factor that inhibits leucocyte migration, which has yet to be isolated and identified, may be a helpful diagnostic tool in patients with suspected lymphoma.", "contents": "Cellular immunity to Hodgkin's splenic tissue measured by leucocyte migration inhibition. Patients with lymphoreticular malignancy were shown by a leucocyte migration inhibition technique to have cellular immunity to Hodgkin's splenic tissue. Migration was significantly inhibited in 31 out of 55 patients with Hodgkin's lymphoma and 19 out of 39 patients with other types of lymphoma. Inhibition was also shown in only three out of 29 patients with other malignancy, one out of 23 normal volunteers, and one out of 25 patients with non-malignant disease. The splenic factor that inhibits leucocyte migration, which has yet to be isolated and identified, may be a helpful diagnostic tool in patients with suspected lymphoma."} {"id": "PMID:1260272", "title": "Detection of somatic muscle fasciculation on electrocardiograms.", "content": "Small discrete spikes appearing on the electrocardiogram (ECG) of a man with a pacemaker turned out to be fasciculation potentials picked up from leg muscles. To find out how common these spikes were all routine ECGs made in one month were reviewed. Spike potentials were found in six patients, and in each case they originated from somatic musculature. Spikes could nearly always be detected on ECGs that were recorded subsequently in patients known to have lower motor neurone lesions that produced fasciculation. Thus the presence of these fasciculation spikes may suggest underlying neuromuscular disease; this possibility should be recognised by those who record ECGs so that the spikes are not suppressed by overuse of the filter.", "contents": "Detection of somatic muscle fasciculation on electrocardiograms. Small discrete spikes appearing on the electrocardiogram (ECG) of a man with a pacemaker turned out to be fasciculation potentials picked up from leg muscles. To find out how common these spikes were all routine ECGs made in one month were reviewed. Spike potentials were found in six patients, and in each case they originated from somatic musculature. Spikes could nearly always be detected on ECGs that were recorded subsequently in patients known to have lower motor neurone lesions that produced fasciculation. Thus the presence of these fasciculation spikes may suggest underlying neuromuscular disease; this possibility should be recognised by those who record ECGs so that the spikes are not suppressed by overuse of the filter."} {"id": "PMID:1260273", "title": "Failure of phenobarbitone to prevent febrile convulsions.", "content": "One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage.", "contents": "Failure of phenobarbitone to prevent febrile convulsions. One-hundred-sixty-five children without known neurological disorder who presented with their first febrile convulsion between the ages of six months and three years were assigned to daily phenobarbitone treatment or to a control group and followed up at a special clinic for six months. One-hundred-and-sixty-one-one children completed the trial, and of the 88 children assigned to phenobarbitone treatment 10 had further convulsions during this period compared with 14 of the 73 control children. Only 49 of those assigned to phenobarbitone took the drug regularly throughout the trial, and four of these had further febrile convulsions, a proportion not significantly different from that in the controls. All four had mean plasma phenobarbitone concentrations over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours over 69 mumol/l (16 mug/ml) during the trial and in three the plasma concentration was at or over this figure within eight hours of the repeat convulsion. Regular phenobarbitone does not seem to prevent febrile convulsions. Attention should instead be directed to organising emergency services to allow early termination of fevrile convulsions, whether first or subsequent, to prevent irreversible brain damage."} {"id": "PMID:1260277", "title": "Medicines and elderly people: a general practice survey.", "content": "All 151 patients of 75 years and over in one practice were visited at home to survey their health and how they managed their medicines. Altogehter 87% were on regular treatment, 34% taking three or four different drugs each day. Most were responsible for their own drugs and managed them well, but many left their drugs in exposed places and were uncertain about how to dispose of unwanted medicines. Overall they were prescribed about three times the number of drugs prescribed for the general population, and women took twice as many drugs regularly as men. Although many drugs were obtained directly from a pharmacist, his advice was rarely sought. Most were labelled, but more explicit instructions about indications for taking the drug would have been helpful, and information about hoarded drugs would have been enhanced by dispensing and expiry dates. Treatment was facilitated when patients brought their drugs to the consultation and careful records were made of repeat prescriptions. As so many patients take three or more different types of drugs each day a container in which a day's supply could be laid out would be useful.", "contents": "Medicines and elderly people: a general practice survey. All 151 patients of 75 years and over in one practice were visited at home to survey their health and how they managed their medicines. Altogehter 87% were on regular treatment, 34% taking three or four different drugs each day. Most were responsible for their own drugs and managed them well, but many left their drugs in exposed places and were uncertain about how to dispose of unwanted medicines. Overall they were prescribed about three times the number of drugs prescribed for the general population, and women took twice as many drugs regularly as men. Although many drugs were obtained directly from a pharmacist, his advice was rarely sought. Most were labelled, but more explicit instructions about indications for taking the drug would have been helpful, and information about hoarded drugs would have been enhanced by dispensing and expiry dates. Treatment was facilitated when patients brought their drugs to the consultation and careful records were made of repeat prescriptions. As so many patients take three or more different types of drugs each day a container in which a day's supply could be laid out would be useful."} {"id": "PMID:1260278", "title": "Resuscitation teaching room in a district general hospital: concept and practice.", "content": "Practical training in cardiopulmonary resuscitation presents a problem because of the shortage of teacher time and the many potential trainees. A resuscitation teaching room in district general hospital has been established, equipped with training mannikins and models, together with wall diagrams and cassette recordings. The arrangement enables many trainees to gain training in small groups with minimal demand on teachers. Experience with the room in use has suggested that the concept may have an application in many district general hospitals and possibly also in large industrial concerns.", "contents": "Resuscitation teaching room in a district general hospital: concept and practice. Practical training in cardiopulmonary resuscitation presents a problem because of the shortage of teacher time and the many potential trainees. A resuscitation teaching room in district general hospital has been established, equipped with training mannikins and models, together with wall diagrams and cassette recordings. The arrangement enables many trainees to gain training in small groups with minimal demand on teachers. Experience with the room in use has suggested that the concept may have an application in many district general hospitals and possibly also in large industrial concerns."} {"id": "PMID:1260308", "title": "Coeliac disease with farmers' lung.", "content": "Two patients with allergic alveolitis due to mouldy hay antigens (farmer's lung) were shown to have malabsorption due to coeliac disease. As similar associations have been found with other alveolar diseases, this association is probably not fortuitous and further population screening should be done.", "contents": "Coeliac disease with farmers' lung. Two patients with allergic alveolitis due to mouldy hay antigens (farmer's lung) were shown to have malabsorption due to coeliac disease. As similar associations have been found with other alveolar diseases, this association is probably not fortuitous and further population screening should be done."} {"id": "PMID:1260318", "title": "Incidence of tuberculosis, hepatitis, brucellosis, and shigellosis in British medical laboratory workers.", "content": "A retrospective postal survey of 21 000 medical laboratory workers in England and Wales showed 18 new cases of pulmonary tuberculosis in 1971, a five-times increased risk of acquiring the disease compared with the general population. Technicians were at greatest risk, especially if they worked in morbid anatomy departments. Of the 35 cases of hepatitis, the technicians were again the occupational group most likely to acquire the disease. Microbiology staff were twice as likely to report shigellosis as those in other pathology divisions but only one case of brucellosis was reported in the whole laboratory population. A similar survey carried out in 1973 of 3000 Scottish medical laboratory workers corroborates the results from England and Wales. Medical laboratory workers continue to experience a considerable risk of developing an occupationally acquired infection. Improvements in staff safety and health care seem to be necessary.", "contents": "Incidence of tuberculosis, hepatitis, brucellosis, and shigellosis in British medical laboratory workers. A retrospective postal survey of 21 000 medical laboratory workers in England and Wales showed 18 new cases of pulmonary tuberculosis in 1971, a five-times increased risk of acquiring the disease compared with the general population. Technicians were at greatest risk, especially if they worked in morbid anatomy departments. Of the 35 cases of hepatitis, the technicians were again the occupational group most likely to acquire the disease. Microbiology staff were twice as likely to report shigellosis as those in other pathology divisions but only one case of brucellosis was reported in the whole laboratory population. A similar survey carried out in 1973 of 3000 Scottish medical laboratory workers corroborates the results from England and Wales. Medical laboratory workers continue to experience a considerable risk of developing an occupationally acquired infection. Improvements in staff safety and health care seem to be necessary."} {"id": "PMID:1260335", "title": "Papers and originals.", "content": "Six cases of persistent non-accidental poisoning of children by their parents are reported. Certain features may draw attention to the diagnosis, particularly bizarre symptoms and signs with no apparent pathological explanation, and toxicological analysis should be carried out to obtain rapid confirmation of the diagnosis. The underlying disorder may include marital conflict, overinvolvement between parent and child, or drug abuse in the parents. A suggested plan of action for managing this problem is outlined.", "contents": "Papers and originals. Six cases of persistent non-accidental poisoning of children by their parents are reported. Certain features may draw attention to the diagnosis, particularly bizarre symptoms and signs with no apparent pathological explanation, and toxicological analysis should be carried out to obtain rapid confirmation of the diagnosis. The underlying disorder may include marital conflict, overinvolvement between parent and child, or drug abuse in the parents. A suggested plan of action for managing this problem is outlined."} {"id": "PMID:1260336", "title": "Complement and meningococcal infection.", "content": "Serum C3 levels were measured in 211 patients with meningococcal disease. Low levels were found in 13 patients with acute meningococcaemia, and complement activation may have contributed to the peripheral circulatory collapse that was responsible for nine deaths. The complement profile of these patients suggested activation of both classical and alternative complement pathways. Patients with meningitis had a higher mean serum C3 level than controls. Serial studies in 13 serum antigen-positive patients with meningitis who subsequently developed arthritis or cutaneous vasculitis showed a transient fall in serum C3 in eight. This fall was probably due to the formation of immune complexes that were responsible for their allergic complications.", "contents": "Complement and meningococcal infection. Serum C3 levels were measured in 211 patients with meningococcal disease. Low levels were found in 13 patients with acute meningococcaemia, and complement activation may have contributed to the peripheral circulatory collapse that was responsible for nine deaths. The complement profile of these patients suggested activation of both classical and alternative complement pathways. Patients with meningitis had a higher mean serum C3 level than controls. Serial studies in 13 serum antigen-positive patients with meningitis who subsequently developed arthritis or cutaneous vasculitis showed a transient fall in serum C3 in eight. This fall was probably due to the formation of immune complexes that were responsible for their allergic complications."} {"id": "PMID:1260337", "title": "Response and survival in advanced breast cancer after two non-cross-resistant combinations.", "content": "A prospective study with two cytotoxic combinations (cyclophosphamide, methotrexate, and fluorouracil (CMF), and adriamycin plus vincristine (AV)) was carried out in 110 patients with advanced breast cancer. There was no significant difference between the treatment groups in the response rate after primary treatment, the median duration of response, and the median survival. In both groups responders survived for longer than non-responders. Secondary treatment after crossover for progression or relapse resulted in response rates of 35% for AV and 20% for CMF. Toxicity was mainly represented by reversible haemosuppression. These results are comparable with those obtained with other multiple-drug regimens, and combination chemotherapy alone seems to have reached a plateau in its capacity to control disseminated breast cancer.", "contents": "Response and survival in advanced breast cancer after two non-cross-resistant combinations. A prospective study with two cytotoxic combinations (cyclophosphamide, methotrexate, and fluorouracil (CMF), and adriamycin plus vincristine (AV)) was carried out in 110 patients with advanced breast cancer. There was no significant difference between the treatment groups in the response rate after primary treatment, the median duration of response, and the median survival. In both groups responders survived for longer than non-responders. Secondary treatment after crossover for progression or relapse resulted in response rates of 35% for AV and 20% for CMF. Toxicity was mainly represented by reversible haemosuppression. These results are comparable with those obtained with other multiple-drug regimens, and combination chemotherapy alone seems to have reached a plateau in its capacity to control disseminated breast cancer."} {"id": "PMID:1260338", "title": "Rheumatoid arthritis and ankylosing spondylitis occurring together.", "content": "Rheumatoid arthritis and ankylosing spondylitis are often difficult to differentiate, though it is important to do so as the natural history and treatment of the two conditions differ. Nine patients have recently been seen, each of whom fulfilled the criteria for both rheumatoid arthritis and ankylosing spondylitis. In eight of the nine patients the histocompatibility antigen HLA-27 was present. A possible explanation of these cases is that one of the diseases occurred by chance in patients already suffering from the other, but this is extremely unlikely. If a chance association is not the correct explanation the basic concepts defining rheumatoid arthritis and ankylosing spondylitis must be reconsidered.", "contents": "Rheumatoid arthritis and ankylosing spondylitis occurring together. Rheumatoid arthritis and ankylosing spondylitis are often difficult to differentiate, though it is important to do so as the natural history and treatment of the two conditions differ. Nine patients have recently been seen, each of whom fulfilled the criteria for both rheumatoid arthritis and ankylosing spondylitis. In eight of the nine patients the histocompatibility antigen HLA-27 was present. A possible explanation of these cases is that one of the diseases occurred by chance in patients already suffering from the other, but this is extremely unlikely. If a chance association is not the correct explanation the basic concepts defining rheumatoid arthritis and ankylosing spondylitis must be reconsidered."} {"id": "PMID:1260339", "title": "False-positive lung scans and radiotherapy.", "content": "It has been suggested that obliterative vasculitis in the lung might mimic pulmonary embolism on a ventilationperfusion scan. The combined scans of six patients with breast cancer who had undergone radiotherapy to the chest wall, which can induce pulmonary vasculitis, were therefore examined. Eleven of the 12 scans showed perfusion defects with ventilation-perfusion mismatch on the irradiated side. Special care is needed in interpreting the lung scans of patients who have received an appreciable tissue dose of radiation to the lungs; mismatch need not indicate pulmonary embolism.", "contents": "False-positive lung scans and radiotherapy. It has been suggested that obliterative vasculitis in the lung might mimic pulmonary embolism on a ventilationperfusion scan. The combined scans of six patients with breast cancer who had undergone radiotherapy to the chest wall, which can induce pulmonary vasculitis, were therefore examined. Eleven of the 12 scans showed perfusion defects with ventilation-perfusion mismatch on the irradiated side. Special care is needed in interpreting the lung scans of patients who have received an appreciable tissue dose of radiation to the lungs; mismatch need not indicate pulmonary embolism."} {"id": "PMID:1260349", "title": "Horner's syndrome and headache due to carotid artery disease.", "content": "Horner's syndrome was accompanied by ipsilateral pain in the head, face, or neck in eight patients. In all cases angiography showed narrowing of the internal carotid artery in a pattern compatible with dissection within the arterial wall. In one patient in whom this diagnosis was substantiated by surgical exploration biopsy of the arterial wall showed changes typical of cystic medial necrosis. It is suggested that this clinical presentation constitutes a distinct syndrome.", "contents": "Horner's syndrome and headache due to carotid artery disease. Horner's syndrome was accompanied by ipsilateral pain in the head, face, or neck in eight patients. In all cases angiography showed narrowing of the internal carotid artery in a pattern compatible with dissection within the arterial wall. In one patient in whom this diagnosis was substantiated by surgical exploration biopsy of the arterial wall showed changes typical of cystic medial necrosis. It is suggested that this clinical presentation constitutes a distinct syndrome."} {"id": "PMID:1260350", "title": "Twelve-minute walking test for assessing disability in chronic bronchitis.", "content": "The distance covered in 12 minutes' walking was used to test exercise tolerance in chronic bronchitis. The distance covered bore a poor relation to the forced expiratory volume in 1 second but a significant relation to the forced vital capacity and the maximum oxygen consumption and ventilation on a bicycle ergometer. The test may be a simple practical guide to everyday disability in chronic bronchitis.", "contents": "Twelve-minute walking test for assessing disability in chronic bronchitis. The distance covered in 12 minutes' walking was used to test exercise tolerance in chronic bronchitis. The distance covered bore a poor relation to the forced expiratory volume in 1 second but a significant relation to the forced vital capacity and the maximum oxygen consumption and ventilation on a bicycle ergometer. The test may be a simple practical guide to everyday disability in chronic bronchitis."} {"id": "PMID:1260384", "title": "Multiple sclerosis among immigrants in Greater London.", "content": "Among immigrants resident in greater London from Europe, Ireland, the USSR, the old Commonwealth countries of Australia, Canada, and New Zealand, North and South America, Egypt, Turkey, and Iran the incidence of admission to hospital for probable multiple sclerosis (MS) between 1960 and 1972 was high or moderately high. The incidence was the same order as that found in those born in the United Kingdom. Immigrants from India, Pakistan, and other Asian countries and from new Commonwealth Africa and America, which includes the West Indies, had a low incidence of hospital admission for MS. Immigrants from countries where the risk of MS is low whose parents were born in Europe had a reduced incidence of admission to hospital but not the very low incidence found in those parents were also born in these countries. Emigrating to England from low risk parts of the world did not seem to increase the risk of developing MS.", "contents": "Multiple sclerosis among immigrants in Greater London. Among immigrants resident in greater London from Europe, Ireland, the USSR, the old Commonwealth countries of Australia, Canada, and New Zealand, North and South America, Egypt, Turkey, and Iran the incidence of admission to hospital for probable multiple sclerosis (MS) between 1960 and 1972 was high or moderately high. The incidence was the same order as that found in those born in the United Kingdom. Immigrants from India, Pakistan, and other Asian countries and from new Commonwealth Africa and America, which includes the West Indies, had a low incidence of hospital admission for MS. Immigrants from countries where the risk of MS is low whose parents were born in Europe had a reduced incidence of admission to hospital but not the very low incidence found in those parents were also born in these countries. Emigrating to England from low risk parts of the world did not seem to increase the risk of developing MS."} {"id": "PMID:1260385", "title": "Defects in sphygmomanometers: an important source of error in blood pressure recording.", "content": "Almost half the sphygmomanometers in a teaching hospital group had defects in the control valve which interfered with accurate blood-pressure reading. Ward staff should be taught to check sphygmomanometers regularly and replace control valves; time consumption and cost are low. The cuffs in general use in these hospitals, and of the standard size sold in Britain, had rubber bags which did not encircle the arm of more than half the patients on whom they were used. This deficiency causes over-reading of blood pressure in obese people. The size of error is uncertain but it should be avoided by adopting a cuff with a longer bag.", "contents": "Defects in sphygmomanometers: an important source of error in blood pressure recording. Almost half the sphygmomanometers in a teaching hospital group had defects in the control valve which interfered with accurate blood-pressure reading. Ward staff should be taught to check sphygmomanometers regularly and replace control valves; time consumption and cost are low. The cuffs in general use in these hospitals, and of the standard size sold in Britain, had rubber bags which did not encircle the arm of more than half the patients on whom they were used. This deficiency causes over-reading of blood pressure in obese people. The size of error is uncertain but it should be avoided by adopting a cuff with a longer bag."} {"id": "PMID:1260394", "title": "Erythema infectiosum: an outbreak of \"slapped cheek\" disease in north Devon.", "content": "An outbreak of erythema infectiosum (fifth disease; megalerythema epidemicum) which occurred in a small north Devon town (population 3600) during the spring of 1975 is reported. All fifty-eight cases displayed the diagnostic \"slapped cheek\" appearance. Virological studies gave disappointingly negative results.", "contents": "Erythema infectiosum: an outbreak of \"slapped cheek\" disease in north Devon. An outbreak of erythema infectiosum (fifth disease; megalerythema epidemicum) which occurred in a small north Devon town (population 3600) during the spring of 1975 is reported. All fifty-eight cases displayed the diagnostic \"slapped cheek\" appearance. Virological studies gave disappointingly negative results."} {"id": "PMID:1260396", "title": "Acute renal failure in tropical Africa.", "content": "Between 1972 and 1975, 55 adult patients with acute renal failure were admitted to the renal unit of Korle Bu Hospital. Fourteen patients died, giving an overall death rate of 25%. Massive intravascular haemolysis after a short febrile illness was the commonest cause of acute renal failure. Clinically these patients presented with blackwater fever but in only one could Plasmodium falciparum malaria be confidently diagnosed. In half the patients various bacterial and viral infections (especially typhoid) could be incriminated as causing this blackwater fever syndrome. The incidence of glucose-6-phosphate dehydrogenase deficiency was 22.5%, but we could not confirm the impression of a greater predisposition to acute renal failure in patients with this enzyme defect.", "contents": "Acute renal failure in tropical Africa. Between 1972 and 1975, 55 adult patients with acute renal failure were admitted to the renal unit of Korle Bu Hospital. Fourteen patients died, giving an overall death rate of 25%. Massive intravascular haemolysis after a short febrile illness was the commonest cause of acute renal failure. Clinically these patients presented with blackwater fever but in only one could Plasmodium falciparum malaria be confidently diagnosed. In half the patients various bacterial and viral infections (especially typhoid) could be incriminated as causing this blackwater fever syndrome. The incidence of glucose-6-phosphate dehydrogenase deficiency was 22.5%, but we could not confirm the impression of a greater predisposition to acute renal failure in patients with this enzyme defect."} {"id": "PMID:1260406", "title": "Detection of gonorrhoea in women.", "content": "A retrospective survey of 210 female patients with gonorrhoea who attended the West London Hospital during 4 months of 1973 showed that nine out of ten were diagnosed by tests taken at the first examination. Ten patients were diagnosed at third or subsequent examinations, but nine of them had defaulted for more than one month before the diagnosis was made, and the tenth gave a clear history of later infection. Three-quarters of the patients came because of known contact with infected males, and less than a quarter of patients who came for this reason were not infected. After one negative post-treatment test, all recurrences were associated with prematurely resumed sexual intercourse or contact with fresh infection. It is concluded that routine repetitive testing is unproductive, and that the tracing of contacts is of paramount importance.", "contents": "Detection of gonorrhoea in women. A retrospective survey of 210 female patients with gonorrhoea who attended the West London Hospital during 4 months of 1973 showed that nine out of ten were diagnosed by tests taken at the first examination. Ten patients were diagnosed at third or subsequent examinations, but nine of them had defaulted for more than one month before the diagnosis was made, and the tenth gave a clear history of later infection. Three-quarters of the patients came because of known contact with infected males, and less than a quarter of patients who came for this reason were not infected. After one negative post-treatment test, all recurrences were associated with prematurely resumed sexual intercourse or contact with fresh infection. It is concluded that routine repetitive testing is unproductive, and that the tracing of contacts is of paramount importance."} {"id": "PMID:1260407", "title": "Minocycline hydrochloride (Minocin) as a single-dose oral treatment of uncomplicated gonorrhoea in men.", "content": "349 male patients with uncomplicated gonococcal urethritis were treated with a single dose of 300 mg. or 400 mg. minocycline hydrochloride. The lower dose gave a lower failure rate, 3-2 compared with 5-1 per cent., but this difference was not statistically significant. The overall known failure rate of 4-2 per cent. compares most favourably with our previous findings in this area using other drugs of the tetracycline group. The incidence of post-gonococcal urethritis (5-1 per cent.) was also the lowest we have found. The few side-effects reported were comparatively trivial. Because of its high degree of therapeutic efficacy, the relatively lack of side-effects, and the reduced incidence of post-gonococcal urethritis, minocycline hydrochloride should be considered the drug of choice whenever single-dose oral treatment is given in uncomplicated gonorrhoea in men.", "contents": "Minocycline hydrochloride (Minocin) as a single-dose oral treatment of uncomplicated gonorrhoea in men. 349 male patients with uncomplicated gonococcal urethritis were treated with a single dose of 300 mg. or 400 mg. minocycline hydrochloride. The lower dose gave a lower failure rate, 3-2 compared with 5-1 per cent., but this difference was not statistically significant. The overall known failure rate of 4-2 per cent. compares most favourably with our previous findings in this area using other drugs of the tetracycline group. The incidence of post-gonococcal urethritis (5-1 per cent.) was also the lowest we have found. The few side-effects reported were comparatively trivial. Because of its high degree of therapeutic efficacy, the relatively lack of side-effects, and the reduced incidence of post-gonococcal urethritis, minocycline hydrochloride should be considered the drug of choice whenever single-dose oral treatment is given in uncomplicated gonorrhoea in men."} {"id": "PMID:1260408", "title": "Studies on ciliated epithelia of the human genital tract. I. Swelling of the cilia of Fallopian tube epithelium in organ cultures infected with Mycoplasma hominis.", "content": "Organ cultures of human Fallopian tubes were infected with Mycoplasma hominis. Scanning and transmission electron microscopy revealed swelling of the cilia of the tubal epithelial cells in infected cultures. In some, the entire cilia were swollen; in others, only the tips. Uninfected cultures kept for up to 7 days showed no structural changes in the cilia or other surface structures. M. hominis multiplied in organ cultures, but not in culture medium without tissue. A practical organ culture technique for the preparation of specimens for electron microscopy is described.", "contents": "Studies on ciliated epithelia of the human genital tract. I. Swelling of the cilia of Fallopian tube epithelium in organ cultures infected with Mycoplasma hominis. Organ cultures of human Fallopian tubes were infected with Mycoplasma hominis. Scanning and transmission electron microscopy revealed swelling of the cilia of the tubal epithelial cells in infected cultures. In some, the entire cilia were swollen; in others, only the tips. Uninfected cultures kept for up to 7 days showed no structural changes in the cilia or other surface structures. M. hominis multiplied in organ cultures, but not in culture medium without tissue. A practical organ culture technique for the preparation of specimens for electron microscopy is described."} {"id": "PMID:1260420", "title": "Dopaminergic substrates of intracranial self-stimulation in the caudate-putamen.", "content": "An extensive mapping of the caudate-putamen in rat for intracranial self-stimulation (ICS) site was undertaken to provide addtional support for the role of dopamine in brain-stimulation reward. Eight-seven per cent of the placements in the neostriatum supported ICS, with self-stimulation rates greater than 250/15 min at 56% of these sites. Electrical stimulation also elicited rearing and clonus, and contralateral body turn, both of which varied in magnitude between animals. In a second experiment, animals were prepared with electrodes aimed at the lateral caudateputamen. Those subjects displaying ICS subsequently received 6-hydroxydopamine lesions to the dopamine cell bodies in the substantia nigra pars compacta, either ipsilateral or contralateral to the electrode. The destruction of the dopamine cell bodies attenuated ICS in both groups during the first post-lesion test sessions. However, the rates in the ipsilateral group declined to between 2 and 9% of control scores, whereas the rate in the contralateral group improved over testing to 72% of control values, 28 days after the lesion. On the basis of these data, it was concluded that unilateral destruction of the dopaminergic nigro-neostriatal bundle (NSB) has two effects on ICS behavior. First, unilateral reduction of neostriatal dopamine is accompanied by a loss of brain-stimulation reward at sites normally innervated by the NSB, specifically the caudate-putamen. Secondly, lesions of the NSB produce a general disruption in bar-pressing behavior, as evidenced by the attenuation of ICS following contralateral lesions.", "contents": "Dopaminergic substrates of intracranial self-stimulation in the caudate-putamen. An extensive mapping of the caudate-putamen in rat for intracranial self-stimulation (ICS) site was undertaken to provide addtional support for the role of dopamine in brain-stimulation reward. Eight-seven per cent of the placements in the neostriatum supported ICS, with self-stimulation rates greater than 250/15 min at 56% of these sites. Electrical stimulation also elicited rearing and clonus, and contralateral body turn, both of which varied in magnitude between animals. In a second experiment, animals were prepared with electrodes aimed at the lateral caudateputamen. Those subjects displaying ICS subsequently received 6-hydroxydopamine lesions to the dopamine cell bodies in the substantia nigra pars compacta, either ipsilateral or contralateral to the electrode. The destruction of the dopamine cell bodies attenuated ICS in both groups during the first post-lesion test sessions. However, the rates in the ipsilateral group declined to between 2 and 9% of control scores, whereas the rate in the contralateral group improved over testing to 72% of control values, 28 days after the lesion. On the basis of these data, it was concluded that unilateral destruction of the dopaminergic nigro-neostriatal bundle (NSB) has two effects on ICS behavior. First, unilateral reduction of neostriatal dopamine is accompanied by a loss of brain-stimulation reward at sites normally innervated by the NSB, specifically the caudate-putamen. Secondly, lesions of the NSB produce a general disruption in bar-pressing behavior, as evidenced by the attenuation of ICS following contralateral lesions."} {"id": "PMID:1260421", "title": "Development of visuomotor behavior in normal and dark-reared cats.", "content": "The development of visuomotor coordination in light-deprived cats was compared with that of newborn animals, raised under normal circumstances, using behavioral tests. Two groups of light-deprived cats were studied: one of which was dark-reared for 4 months, the other for 7 months. After dark-rearing the cats were kept in animal rooms which were illuminated for 12 h each day. All cats spent at least 4 h each day in a big playroom, where toys were available. Obstacle avoidance, tracking of moving objects, optokinetic nystagmus, visually triggered extension, visually guided placing, visual cliff behavior and jumping were tested. All light-deprived cats revealed a complete recovery of visuomotor behavior; the 7-months deprived cats recovered within 10 weeks and the 4-months deprived ones within 7 weeks. The time period in which the various responses in both groups of light-deprived cats developed after dark-rearing was found to be roughly in accordance with that of normally visually inexperienced kittens after birth.", "contents": "Development of visuomotor behavior in normal and dark-reared cats. The development of visuomotor coordination in light-deprived cats was compared with that of newborn animals, raised under normal circumstances, using behavioral tests. Two groups of light-deprived cats were studied: one of which was dark-reared for 4 months, the other for 7 months. After dark-rearing the cats were kept in animal rooms which were illuminated for 12 h each day. All cats spent at least 4 h each day in a big playroom, where toys were available. Obstacle avoidance, tracking of moving objects, optokinetic nystagmus, visually triggered extension, visually guided placing, visual cliff behavior and jumping were tested. All light-deprived cats revealed a complete recovery of visuomotor behavior; the 7-months deprived cats recovered within 10 weeks and the 4-months deprived ones within 7 weeks. The time period in which the various responses in both groups of light-deprived cats developed after dark-rearing was found to be roughly in accordance with that of normally visually inexperienced kittens after birth."} {"id": "PMID:1260422", "title": "Acetylcholine release from visual and sensorimotor cortices of conditioned rabbits: the effects of sensory cuing and patterns of responding.", "content": "A technique was devised for the collection of acetylcholine (ACh) released from the cerebral cortex of awake rabbits while they were performing a previously learned operant task. Based on the assumption that ACh release is directly proportional to the activity of cholinergic synapses under the area of collection, two hypotheses of the functional role of cortical cholinergic mechanisms were examined: (1) that activity in cholinergic neurons is related to the inhibition of responding; (2) that cholinergic activity is related to the perception of a 'significant' stimulus. Five groups trained on different behavioral paradigms were used to test these hypotheses. ACh release was collected concurrently from visual and sensorimotor cortices to differentiate diffuse from specific cortical effects. A small (50-100%) increase in ACh release was found in all groups and from both cortical areas. In the case of one group (visually cued, reinforced for low response rates) a significantly greater increase occurred from sensorimotor cortex only. These findings do not support either hypothesis alone, and are interpreted as evidence for two cholinergic systems within, or projecting to the cortex. One is related to generalized behavioral arousal and desynchronization of the electroencephalogram. Activation of the second cholinergic system is dependent on both response inhibition and the presence of a significant stimulus of the visual (but not of the auditory) modality.", "contents": "Acetylcholine release from visual and sensorimotor cortices of conditioned rabbits: the effects of sensory cuing and patterns of responding. A technique was devised for the collection of acetylcholine (ACh) released from the cerebral cortex of awake rabbits while they were performing a previously learned operant task. Based on the assumption that ACh release is directly proportional to the activity of cholinergic synapses under the area of collection, two hypotheses of the functional role of cortical cholinergic mechanisms were examined: (1) that activity in cholinergic neurons is related to the inhibition of responding; (2) that cholinergic activity is related to the perception of a 'significant' stimulus. Five groups trained on different behavioral paradigms were used to test these hypotheses. ACh release was collected concurrently from visual and sensorimotor cortices to differentiate diffuse from specific cortical effects. A small (50-100%) increase in ACh release was found in all groups and from both cortical areas. In the case of one group (visually cued, reinforced for low response rates) a significantly greater increase occurred from sensorimotor cortex only. These findings do not support either hypothesis alone, and are interpreted as evidence for two cholinergic systems within, or projecting to the cortex. One is related to generalized behavioral arousal and desynchronization of the electroencephalogram. Activation of the second cholinergic system is dependent on both response inhibition and the presence of a significant stimulus of the visual (but not of the auditory) modality."} {"id": "PMID:1260423", "title": "Relation of axon membrane to myelin membrane in sciatic nerve during development: comparison of morphological and chemical parameters.", "content": "The relationship of axon circumference to myelin area on cross-section both for myelinated and total fibres has been estimated at a mid-point in the sciatic nerve of two rabbits, one newborn and the other 20 weeks old. The slopes of the regression lines relating myelin area to axon circumference for myelinated fibres were 0.72 (standard error 0.03) with a correlation coefficient of 0.81 in the newborn nerve and 2.96 (standard error 0.05) with correlation coefficient of 0.96 in the 20-week nerve. Using the above parameters, and assuming constant thickness of axolemma and constant packing density of myelin, a correlation was made of the change in relationship of axolemma volume of myelinated fibres to myelin volume in the nerve between the two ages with the changes in content of two membrane lipids, ganglioside and cerebroside. This revealed a constant relationship of morphological to chemical parameters at the two ages although the proportion of unmyelinated fibres was much greater in the newborn. If cerebroside is regarded as a marker for myelin membrane, this observation suggests an association of gangliosides with myelination in peripheral nerve.", "contents": "Relation of axon membrane to myelin membrane in sciatic nerve during development: comparison of morphological and chemical parameters. The relationship of axon circumference to myelin area on cross-section both for myelinated and total fibres has been estimated at a mid-point in the sciatic nerve of two rabbits, one newborn and the other 20 weeks old. The slopes of the regression lines relating myelin area to axon circumference for myelinated fibres were 0.72 (standard error 0.03) with a correlation coefficient of 0.81 in the newborn nerve and 2.96 (standard error 0.05) with correlation coefficient of 0.96 in the 20-week nerve. Using the above parameters, and assuming constant thickness of axolemma and constant packing density of myelin, a correlation was made of the change in relationship of axolemma volume of myelinated fibres to myelin volume in the nerve between the two ages with the changes in content of two membrane lipids, ganglioside and cerebroside. This revealed a constant relationship of morphological to chemical parameters at the two ages although the proportion of unmyelinated fibres was much greater in the newborn. If cerebroside is regarded as a marker for myelin membrane, this observation suggests an association of gangliosides with myelination in peripheral nerve."} {"id": "PMID:1260424", "title": "Regional and subcellular [3h]estradiol localization in selected brain regions and pituitary of female mice: effects of unlabeled estradiol and various anti-hormones.", "content": "Groups of ovariectomized mice were pretreated for 30 min with either vehicle, unlabeled estradiol benzoate or one of the following anti-hormones: cyproterone acetate, CI-628 or CN-69, 725-27. One hour after an I.V. injection of [3H]estradiol the levels of toluence extractable radioactivity retained in the crude nuclear and cytosol fractions of selected brain regions, pituitary and plasma were determined by liquid scintillation spectrometry. The major findings were: (1) In vehicle treated animals [3H]estradiol uptake in the pituitary greatly exceeded that in all brain regions. Within the brain uptake was greatest in the preoptic anterior hypothalamus (POA-AH) and medial basal hypothalamus (MBH) samples. Nuclear uptake exceeded cytosol uptake only in the pituitary and POA-AH and MBH samples. (2) Estradiol benzoate pretreatment greatly reduced nuclear, and to a lesser extent cytosol [3H]estradiol uptake in pituitary, POA-AH and MBH samples. Estradiol benzoate pretreatment also reduced nuclear uptake in the dorsal middle hypothalamus (DMH). (3) The anti-androgen cyproterone acetate, previously shown to have anti-estrogenic effects in female sexual behavior tests, was found to have no effect on nuclear or cytosol [3H]estradiol uptake in brain and pituitary. (4) The anti-estrogen CI-628 was found to reduce nuclear [3H]estradiol uptake in the POA-AH and pituitary samples. It also reduced cytosol [3H]estradiol uptake in the pituitary sample. The anti-estrogen CN-69, 725-27 produced a much greater inhibition of nuclear [3H]estradiol uptake than CI-628 in the POA-AH, MBH, DMH, dorsal posterior hypothalamus and pituitary samples. This anti-estrogen also reduced cytosol [3H]estradiol uptake in the POA-AH, MBH and pituitary samples. (5) A preliminary chromatographic analysis of vehicle control samples indicated that 70-98% of the nuclear radioactivity in target regions such as POA-AH, MBH and pituitary was iso-polar with authentic estradiol, while less than 50% of the radioactivity in plasma and cortex behaved as estradiol.", "contents": "Regional and subcellular [3h]estradiol localization in selected brain regions and pituitary of female mice: effects of unlabeled estradiol and various anti-hormones. Groups of ovariectomized mice were pretreated for 30 min with either vehicle, unlabeled estradiol benzoate or one of the following anti-hormones: cyproterone acetate, CI-628 or CN-69, 725-27. One hour after an I.V. injection of [3H]estradiol the levels of toluence extractable radioactivity retained in the crude nuclear and cytosol fractions of selected brain regions, pituitary and plasma were determined by liquid scintillation spectrometry. The major findings were: (1) In vehicle treated animals [3H]estradiol uptake in the pituitary greatly exceeded that in all brain regions. Within the brain uptake was greatest in the preoptic anterior hypothalamus (POA-AH) and medial basal hypothalamus (MBH) samples. Nuclear uptake exceeded cytosol uptake only in the pituitary and POA-AH and MBH samples. (2) Estradiol benzoate pretreatment greatly reduced nuclear, and to a lesser extent cytosol [3H]estradiol uptake in pituitary, POA-AH and MBH samples. Estradiol benzoate pretreatment also reduced nuclear uptake in the dorsal middle hypothalamus (DMH). (3) The anti-androgen cyproterone acetate, previously shown to have anti-estrogenic effects in female sexual behavior tests, was found to have no effect on nuclear or cytosol [3H]estradiol uptake in brain and pituitary. (4) The anti-estrogen CI-628 was found to reduce nuclear [3H]estradiol uptake in the POA-AH and pituitary samples. It also reduced cytosol [3H]estradiol uptake in the pituitary sample. The anti-estrogen CN-69, 725-27 produced a much greater inhibition of nuclear [3H]estradiol uptake than CI-628 in the POA-AH, MBH, DMH, dorsal posterior hypothalamus and pituitary samples. This anti-estrogen also reduced cytosol [3H]estradiol uptake in the POA-AH, MBH and pituitary samples. (5) A preliminary chromatographic analysis of vehicle control samples indicated that 70-98% of the nuclear radioactivity in target regions such as POA-AH, MBH and pituitary was iso-polar with authentic estradiol, while less than 50% of the radioactivity in plasma and cortex behaved as estradiol."} {"id": "PMID:1260425", "title": "An autoradiographic study of gliogenesis in the rat lateral geniculate nucleus (LGN).", "content": "Rats pregnant for 14, 16, 18 and 20 days, as well as 1-, 3-, 7-, 12-, 16- and 21-day-old offspring, received a single injection of [3H]thymidine and were killed at postnatal ages of 22-27 days. An autoradiographic study of DNA synthesis revealed that proliferation of non-neuronal matrix cell precursors destined for the dorsal part of the lateral geniculate nucleus had already started by gestational day 14. Quantiative evaluation of the incidence of labelled cells revealed 2 peaks occurring in both groups of non-neuronal cells at postnatal days (PD) 7 and 16. It has been assumed that the accelerated production of ectodermally derived glial cells, observed towards PD 7, relfects the enhanced growth of the neuronal surface covered with glial cell processes, and that at PD 16 formation of myelin sheaths. Changes in the number of labelled cells of mesodermal origin in the course of development can probably be attributed to the rate of vasculogenesis of the studied region.", "contents": "An autoradiographic study of gliogenesis in the rat lateral geniculate nucleus (LGN). Rats pregnant for 14, 16, 18 and 20 days, as well as 1-, 3-, 7-, 12-, 16- and 21-day-old offspring, received a single injection of [3H]thymidine and were killed at postnatal ages of 22-27 days. An autoradiographic study of DNA synthesis revealed that proliferation of non-neuronal matrix cell precursors destined for the dorsal part of the lateral geniculate nucleus had already started by gestational day 14. Quantiative evaluation of the incidence of labelled cells revealed 2 peaks occurring in both groups of non-neuronal cells at postnatal days (PD) 7 and 16. It has been assumed that the accelerated production of ectodermally derived glial cells, observed towards PD 7, relfects the enhanced growth of the neuronal surface covered with glial cell processes, and that at PD 16 formation of myelin sheaths. Changes in the number of labelled cells of mesodermal origin in the course of development can probably be attributed to the rate of vasculogenesis of the studied region."} {"id": "PMID:1260441", "title": "The growth and myelination of central and peripheral segments of ventral motoneurone axons. A quantitative ultrastructural study.", "content": "This study compares the growth and myelination of those parts of cervical ventral motoneurone axons in the spinal cord (the intramedullary segments) and in the ventral roots of fetal and young rats (up to 21 days postnatal). The same fibre bundles are examined centrally and peripherally. Myelination begins centrally and peripherally at about birth. However, the peripheral segments of some fibres may begin to become myelinated before the central. Over the first 3 weeks after birth the minimum circumference of peripheral segments of myelinated axons remains relatively constant at 3 mum but that of central segments falls from 2.5 mum to just over 1 mum. Axons within the same fibre bundles tend to be thinner and less heavily myelinated centrally than peripherally. With ageing, axon circumference becomes more strongly correlated with sheath thickness. The thickness of the sheath surrounding an axon of a given circumference does not differ statistically from one age to another or between central and peripheral segments. Studies of myelin sheath growth rate show that in the early stages glial and Schwann cells vary independently of one another in the rates at which they add new turns to sheaths around central and peripheral segments of axons in the same bundles.", "contents": "The growth and myelination of central and peripheral segments of ventral motoneurone axons. A quantitative ultrastructural study. This study compares the growth and myelination of those parts of cervical ventral motoneurone axons in the spinal cord (the intramedullary segments) and in the ventral roots of fetal and young rats (up to 21 days postnatal). The same fibre bundles are examined centrally and peripherally. Myelination begins centrally and peripherally at about birth. However, the peripheral segments of some fibres may begin to become myelinated before the central. Over the first 3 weeks after birth the minimum circumference of peripheral segments of myelinated axons remains relatively constant at 3 mum but that of central segments falls from 2.5 mum to just over 1 mum. Axons within the same fibre bundles tend to be thinner and less heavily myelinated centrally than peripherally. With ageing, axon circumference becomes more strongly correlated with sheath thickness. The thickness of the sheath surrounding an axon of a given circumference does not differ statistically from one age to another or between central and peripheral segments. Studies of myelin sheath growth rate show that in the early stages glial and Schwann cells vary independently of one another in the rates at which they add new turns to sheaths around central and peripheral segments of axons in the same bundles."} {"id": "PMID:1260442", "title": "Electron microscopic evidence for a transsynaptic migration of tetanus toxin in spinal cord motoneurons: an autoradiographic and morphometric study.", "content": "Adult rats were injected intramuscularly (musculus deltoideus) with 125I-labeled tetanus toxin. First signs of tetanic rigidity became visible 12-13 h after injection: death occurred 1-2 h later. Electron microscopic autoradiography of the ventrolateral spinal cord gray matter showed a large part of the radioactivity to be located in motoneurons (perikaryon, axon and dendrites) at 7 and 14 h after injection. A great majority of the rest of the label was found over synaptic terminals, most of them were afferent to motoneurons. The percentage of labeled nerve terminals increased significantly (P less than 0.05) between 7 h and 14 h after injection. Glial elements surrounding the motoneurons were mostly unlabeled. These observations strongly favor the assumption of a transsynaptic migration of tetanus toxin. Dorsal root, dorsal horn and cell bodies of spinal cord interneurons were free of label.", "contents": "Electron microscopic evidence for a transsynaptic migration of tetanus toxin in spinal cord motoneurons: an autoradiographic and morphometric study. Adult rats were injected intramuscularly (musculus deltoideus) with 125I-labeled tetanus toxin. First signs of tetanic rigidity became visible 12-13 h after injection: death occurred 1-2 h later. Electron microscopic autoradiography of the ventrolateral spinal cord gray matter showed a large part of the radioactivity to be located in motoneurons (perikaryon, axon and dendrites) at 7 and 14 h after injection. A great majority of the rest of the label was found over synaptic terminals, most of them were afferent to motoneurons. The percentage of labeled nerve terminals increased significantly (P less than 0.05) between 7 h and 14 h after injection. Glial elements surrounding the motoneurons were mostly unlabeled. These observations strongly favor the assumption of a transsynaptic migration of tetanus toxin. Dorsal root, dorsal horn and cell bodies of spinal cord interneurons were free of label."} {"id": "PMID:1260443", "title": "Ultrastructure and synaptic contacts in barrels of mouse SI cortex.", "content": "Barrels in the posteromedial barrel subfield (PMBSF) in layer IV of mouse somatosensory cortex are consistently identifiable and somatotopically related to the large whiskers on the animal's snout32,38. This is a study of the ultrastructure - in particular the synaptic connections - of mouse PMBSF barrels. A technique was developed which enabled the precise selection for electron microscopy of specific regions of barrels identified in the light microscope. Barrel \"sides\" containing a high density of neuronal cell bodies and myelinated axons, contrasted with barrel \"hollows\" in which these elements were relatively sparse. The types and frequencies of synapses were examined in series of thin sections through sides and/or hollows of barrels B2, C3, C7, D4, E4, E5, and E8 from 6 mice. In all, 3042 synapses from 20 fields, each at least 10 mum x 10 mum x 4.8 mum in size, were classified. Four distinct kinds of presynaptic terminal were identified: (1) darkly, and (2) lightly stained, asymmetrically synapsing terminals (AD, AL respectively), and (3) darkly, and (4) lightly stained, symmetrically synapsing terminals (SD, SL respectively). Synapses of these terminals were distributed in roughly similar proportions throughout the neuropil of barrel sides and hollows. Thus in all barrel regions approximately 92% of the synapses in neuropil were made by AD terminals, 1.0% by AL, 2.4% by SD and 4.0% by SL terminals.", "contents": "Ultrastructure and synaptic contacts in barrels of mouse SI cortex. Barrels in the posteromedial barrel subfield (PMBSF) in layer IV of mouse somatosensory cortex are consistently identifiable and somatotopically related to the large whiskers on the animal's snout32,38. This is a study of the ultrastructure - in particular the synaptic connections - of mouse PMBSF barrels. A technique was developed which enabled the precise selection for electron microscopy of specific regions of barrels identified in the light microscope. Barrel \"sides\" containing a high density of neuronal cell bodies and myelinated axons, contrasted with barrel \"hollows\" in which these elements were relatively sparse. The types and frequencies of synapses were examined in series of thin sections through sides and/or hollows of barrels B2, C3, C7, D4, E4, E5, and E8 from 6 mice. In all, 3042 synapses from 20 fields, each at least 10 mum x 10 mum x 4.8 mum in size, were classified. Four distinct kinds of presynaptic terminal were identified: (1) darkly, and (2) lightly stained, asymmetrically synapsing terminals (AD, AL respectively), and (3) darkly, and (4) lightly stained, symmetrically synapsing terminals (SD, SL respectively). Synapses of these terminals were distributed in roughly similar proportions throughout the neuropil of barrel sides and hollows. Thus in all barrel regions approximately 92% of the synapses in neuropil were made by AD terminals, 1.0% by AL, 2.4% by SD and 4.0% by SL terminals."} {"id": "PMID:1260444", "title": "Synaptic actions of tectofugal pathways on abducens motoneurons in the cat.", "content": "Organization of pathways between the superior colliculus (CS) and abducens motoneurons (VI-MNs) was studied in cats under pentobarbital anesthesia using intracellular recordings from VI-MNs and adjacent reticular neurons. Latencies of EPSPs elicited by contralateral CS stimulation indicate that a small fraction of the excitatory pathway may be monosynaptic while its major part is disynaptic. As suggested by an analysis of synaptic responses to microstimulation of the paramedian pontine region, excitatory impulses descend in the tectobulbospinal tract after crossing at midbrain levels. An attempt was made to identify interneurons of the excitatory tectoabducens pathway in the region just ventral and rostroventral to the VI-nucleus. About one-quarter of the reticular neurons in this region received monosynaptic excitation specifically from the contralateral CS. They were acceptable as interneurons with regard to other response characteristics too. Axonal projection to, or through, the abducens nucleus was demonstrated for some of them by intranuclear microstimulation or by tracing axons after Procion yellow injections. It is suggested that \"premotor\" interneurons of the excitatory tectoabducens pathway are concentrated in the vicinity of the abducens nucleic. A similar investigation of inhibitory responses to ipsilateral CS-stimulation indicates that inhibitory pathways are at least disynaptic and, for the most part, contain three or more synapses. In its initial trajectory the inhibitory pathway appears to be identical with the tectobulbospinal tract,but it decussates for the second time at caudal pontine levels to reach ipsilateral VI-MNs.", "contents": "Synaptic actions of tectofugal pathways on abducens motoneurons in the cat. Organization of pathways between the superior colliculus (CS) and abducens motoneurons (VI-MNs) was studied in cats under pentobarbital anesthesia using intracellular recordings from VI-MNs and adjacent reticular neurons. Latencies of EPSPs elicited by contralateral CS stimulation indicate that a small fraction of the excitatory pathway may be monosynaptic while its major part is disynaptic. As suggested by an analysis of synaptic responses to microstimulation of the paramedian pontine region, excitatory impulses descend in the tectobulbospinal tract after crossing at midbrain levels. An attempt was made to identify interneurons of the excitatory tectoabducens pathway in the region just ventral and rostroventral to the VI-nucleus. About one-quarter of the reticular neurons in this region received monosynaptic excitation specifically from the contralateral CS. They were acceptable as interneurons with regard to other response characteristics too. Axonal projection to, or through, the abducens nucleus was demonstrated for some of them by intranuclear microstimulation or by tracing axons after Procion yellow injections. It is suggested that \"premotor\" interneurons of the excitatory tectoabducens pathway are concentrated in the vicinity of the abducens nucleic. A similar investigation of inhibitory responses to ipsilateral CS-stimulation indicates that inhibitory pathways are at least disynaptic and, for the most part, contain three or more synapses. In its initial trajectory the inhibitory pathway appears to be identical with the tectobulbospinal tract,but it decussates for the second time at caudal pontine levels to reach ipsilateral VI-MNs."} {"id": "PMID:1260445", "title": "EEG development in normal and undernourished rats.", "content": "The development of EEG was studied in normal and undernourished white and black hooded rats, aged 9-30 days. Undernutrition of the young was accomplished by underfeeding the mothers with restricted amounts of a standard laboratory food from the 7th day after conception until the 21st day after birth. Bipolar EEG recordings were made from the sensorimotor cortex and from the visual cortex in rats with chronically implanted electrodes. The EEG was recorded, stored on magnetic tape and analyzed for amplitude distributions and frequency spectra. During the recording 3 behavioural states (defined on the basis of behavioural criteria) were distinguished.", "contents": "EEG development in normal and undernourished rats. The development of EEG was studied in normal and undernourished white and black hooded rats, aged 9-30 days. Undernutrition of the young was accomplished by underfeeding the mothers with restricted amounts of a standard laboratory food from the 7th day after conception until the 21st day after birth. Bipolar EEG recordings were made from the sensorimotor cortex and from the visual cortex in rats with chronically implanted electrodes. The EEG was recorded, stored on magnetic tape and analyzed for amplitude distributions and frequency spectra. During the recording 3 behavioural states (defined on the basis of behavioural criteria) were distinguished."} {"id": "PMID:1260454", "title": "Somatotopic localization in cat motor cortex.", "content": "Punctate intracortical stimulation of the motor cortex (areas 4 and 6), with parallel observation of the induced movements, permits description of a fine somatotopic organization of the motor control areas for different parts of the musculature in freely moving adult cats. The results show that movements produced by electrical stimulation of the motor cortex are always single and non-repetitive, regardless of the duration and intensity of the stimulation. These movements are restricted to a very precise part of the musculature, and experiments show that this localization is related to the exact position of the tip of the stimulating electrode in the motor cortex. Other experimental data show that motor responses which disturb the animal's equilibrium are accompanied by postural adjustments. Stimulation of the cerebral cortex permits the definition of a separate motor control area for each part of the cat musculature, with an individual control area for each of the joints of the forelimb. This was not possible for the hindlimb, which is always activated in its entirety. These results establish a new representation of the somatotopic organization of the cat motor cortex. This diagram shows that area 6 controls the more axial parts of the musculature, while area 4 controls the proximal and distal parts of the limb muscles. This map was compared to numerous previous data on the somatotopic organization in the cat motor cortex, especially to the map of Woolsey.", "contents": "Somatotopic localization in cat motor cortex. Punctate intracortical stimulation of the motor cortex (areas 4 and 6), with parallel observation of the induced movements, permits description of a fine somatotopic organization of the motor control areas for different parts of the musculature in freely moving adult cats. The results show that movements produced by electrical stimulation of the motor cortex are always single and non-repetitive, regardless of the duration and intensity of the stimulation. These movements are restricted to a very precise part of the musculature, and experiments show that this localization is related to the exact position of the tip of the stimulating electrode in the motor cortex. Other experimental data show that motor responses which disturb the animal's equilibrium are accompanied by postural adjustments. Stimulation of the cerebral cortex permits the definition of a separate motor control area for each part of the cat musculature, with an individual control area for each of the joints of the forelimb. This was not possible for the hindlimb, which is always activated in its entirety. These results establish a new representation of the somatotopic organization of the cat motor cortex. This diagram shows that area 6 controls the more axial parts of the musculature, while area 4 controls the proximal and distal parts of the limb muscles. This map was compared to numerous previous data on the somatotopic organization in the cat motor cortex, especially to the map of Woolsey."} {"id": "PMID:1260455", "title": "Isolation of dendrodendritic synapses from swine olfactory bulbs.", "content": "Dendrodendritic synapses from swine olfactory bulbs were isolated by homogenization of the gray layer, followed by centrifugation at 1000 X g. Centrifugation of the supernatant at 10,000 X g revealed that all dendrodendritic synapses had pelleted at 1000 X g. The upper portion of the 1000 X g pellet was further purified in a discontinuous sucrose gradient, and each resultant fraction was examined by electron microscopy. The dendrodendritic synapses band below the 1.2-1.4 M sucrose interface, appear to be minimally contaminated with other membranous elements, and have retained their adhesions. The banding pattern and relative amounts of proteins from dendrodendritic synaptosomes were very similar to those of axonal synaptosomes as determined by electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate (SDS) and 8 M urea.", "contents": "Isolation of dendrodendritic synapses from swine olfactory bulbs. Dendrodendritic synapses from swine olfactory bulbs were isolated by homogenization of the gray layer, followed by centrifugation at 1000 X g. Centrifugation of the supernatant at 10,000 X g revealed that all dendrodendritic synapses had pelleted at 1000 X g. The upper portion of the 1000 X g pellet was further purified in a discontinuous sucrose gradient, and each resultant fraction was examined by electron microscopy. The dendrodendritic synapses band below the 1.2-1.4 M sucrose interface, appear to be minimally contaminated with other membranous elements, and have retained their adhesions. The banding pattern and relative amounts of proteins from dendrodendritic synaptosomes were very similar to those of axonal synaptosomes as determined by electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate (SDS) and 8 M urea."} {"id": "PMID:1260456", "title": "A microelectrode study of amygdaloid afferents: temporal neocortical inputs.", "content": "Acute experiments were performed on anesthetized cats using standard techniques of electrical stimulation and single unit recording in order to study the responses of amygdaloid neurons to neocortical inputs. Satisfactory records were obtained from 272 amygdaloid neurons. The majority of those fired spontaneously, at low rates, with single, randomly occurring spikes. The lateral neocortex, particularly the portion which is homologous to temporo-insular cortex in man, is capable of influencing the discharges of many amygdaloid neurons. The typical response pattern consisted of an excitatory-inhibitory sequence with the median onset latency of 12.0 msec, which is consistent with monosynaptic excitation of the output-type nerve cells in the affected regions of the amygdala (Al, Ac, Ab). There was an absence of clear topographical arrangement: all of the effective neocortical areas influenced the neuronal discharges in Al, Ac and Ab fairly equally. These results correlate well with neuroanatomical studies of amygdaloid structure and connectivity. Our finding of diffuse non-topographic excitatory influence upon the lateral, central and basal amygdaloid nuclei exerted by insular-temporal regions known to be involved with higher order sensory analysis and pattern recognition is quite consistent with a view of this system serving as a link between neocortical information stores and the fundamental motivational drive mechanisms of the hypothalamus.", "contents": "A microelectrode study of amygdaloid afferents: temporal neocortical inputs. Acute experiments were performed on anesthetized cats using standard techniques of electrical stimulation and single unit recording in order to study the responses of amygdaloid neurons to neocortical inputs. Satisfactory records were obtained from 272 amygdaloid neurons. The majority of those fired spontaneously, at low rates, with single, randomly occurring spikes. The lateral neocortex, particularly the portion which is homologous to temporo-insular cortex in man, is capable of influencing the discharges of many amygdaloid neurons. The typical response pattern consisted of an excitatory-inhibitory sequence with the median onset latency of 12.0 msec, which is consistent with monosynaptic excitation of the output-type nerve cells in the affected regions of the amygdala (Al, Ac, Ab). There was an absence of clear topographical arrangement: all of the effective neocortical areas influenced the neuronal discharges in Al, Ac and Ab fairly equally. These results correlate well with neuroanatomical studies of amygdaloid structure and connectivity. Our finding of diffuse non-topographic excitatory influence upon the lateral, central and basal amygdaloid nuclei exerted by insular-temporal regions known to be involved with higher order sensory analysis and pattern recognition is quite consistent with a view of this system serving as a link between neocortical information stores and the fundamental motivational drive mechanisms of the hypothalamus."} {"id": "PMID:1260457", "title": "Excitatory effects of 5-hydroxytryptamine, histamine and potassium ions on muscular group IV afferent units: a comparison with bradykinin.", "content": "The excitation of muscular group IV afferent units by the pain-producing substances 5-hydroxytryptamine (5-HT), histamine, and potassium ions was studied in cats and compared with the bradykinin effects of an earlier investigation. The substances were injected into the sural artery and the action potentials of single group IV afferent fibres from the gastrocnemius-soleus muscle were recorded extracellularly. About half of the 180 units tested with chemical stimulation could be excited by amounts of the above agents which are likely to be present in pathologically altered tissues. Of the tested substances, 5-HT was the most and potassium the least effective stimulant; in comparison with bradykinin, 5-HT was by far less potent, though. The molar ratios of approximately equivalent doses of bradykinin, 5-HT, histamine, and potassium were found to be about 1:30:66:4000. The threshold injection doses of KC1 for activation of muscular group IV units were such that an unspecific depolarizaing mode of action seems probable. Differences in the chemosensitivity of individual group IV units might be indicative of the existence of different receptor sites at the nerve endings. The sensitivity of muscle receptors with group IV afferent fibres to pain-producing substances--especially to bradykinin and 5-HT--supports the view that these units might participate in the mediation of muscle pain.", "contents": "Excitatory effects of 5-hydroxytryptamine, histamine and potassium ions on muscular group IV afferent units: a comparison with bradykinin. The excitation of muscular group IV afferent units by the pain-producing substances 5-hydroxytryptamine (5-HT), histamine, and potassium ions was studied in cats and compared with the bradykinin effects of an earlier investigation. The substances were injected into the sural artery and the action potentials of single group IV afferent fibres from the gastrocnemius-soleus muscle were recorded extracellularly. About half of the 180 units tested with chemical stimulation could be excited by amounts of the above agents which are likely to be present in pathologically altered tissues. Of the tested substances, 5-HT was the most and potassium the least effective stimulant; in comparison with bradykinin, 5-HT was by far less potent, though. The molar ratios of approximately equivalent doses of bradykinin, 5-HT, histamine, and potassium were found to be about 1:30:66:4000. The threshold injection doses of KC1 for activation of muscular group IV units were such that an unspecific depolarizaing mode of action seems probable. Differences in the chemosensitivity of individual group IV units might be indicative of the existence of different receptor sites at the nerve endings. The sensitivity of muscle receptors with group IV afferent fibres to pain-producing substances--especially to bradykinin and 5-HT--supports the view that these units might participate in the mediation of muscle pain."} {"id": "PMID:1260458", "title": "GDEE antagonism of iontophoretic amino acid excitations in the intact hippocampus and in the hippocampal slice preparation.", "content": "Glutamic acid diethylester (GDEE) reversibly antagonized excitations produced by glutamate and aspartate but not those produced by acetylcholine when applied iontophoretically to rat CA1 hippocampal neurons in penthrane (methoxyfluorane) anesthetized rats and to CA1 neurons in in vitro slice preparations. GDEE did not appear to differentiate between the excitations produced by glutamate aspartate and appeared to be a more potent antagonist than has previously been reported. CA1 cells were remarkably sensitive to acetylcholine; 5-50 nA being sufficient to produce marked amino acid-like excitations, which were unrelated to the pH of the acetylcholine. The nature of the responses to applied substances was virtually identical between the intact animal and the in vitro slice preparation. A description of the in vitro technique is given as an Appendix.", "contents": "GDEE antagonism of iontophoretic amino acid excitations in the intact hippocampus and in the hippocampal slice preparation. Glutamic acid diethylester (GDEE) reversibly antagonized excitations produced by glutamate and aspartate but not those produced by acetylcholine when applied iontophoretically to rat CA1 hippocampal neurons in penthrane (methoxyfluorane) anesthetized rats and to CA1 neurons in in vitro slice preparations. GDEE did not appear to differentiate between the excitations produced by glutamate aspartate and appeared to be a more potent antagonist than has previously been reported. CA1 cells were remarkably sensitive to acetylcholine; 5-50 nA being sufficient to produce marked amino acid-like excitations, which were unrelated to the pH of the acetylcholine. The nature of the responses to applied substances was virtually identical between the intact animal and the in vitro slice preparation. A description of the in vitro technique is given as an Appendix."} {"id": "PMID:1260459", "title": "Motor and behavioral responses obtained by stimulation with chronic electrodes of the optic lobe of Sepia officinalis.", "content": "A new technique using a stimulating chronically-implanted electrode has allowed us to study the motor responses induced by electrical stimulation of the optic lobe in a freely swimming Sepia. Electrical stimulation of the cortex of the optic lobe produces no motor response; this is in agreement with the results of preceding authors. The stimulation of the neuropil of the optic lobe by monopolar electrode produces many different motor responses, in support of Boycott's results obtained by the same type of excitation in acute experiments. However, the field of stimulation of these electrodes could not always have been the same and it is possible that we were sometimes stimulating nervous structures close to the optic lobe. Stimulation by a bipolar electrode, however, which does not have this advantage, induces only two very different motor responses: an ipsilateral rotation and an 'alarm reaction\", so called because of its similarities to the 'attentive immobilization\" of higher vertebrates. These two reactions are very complex and their different components are linked together as in a behavioural response from an intact animal. These reactions present very different characteristics of excitability. They are obtained from many areas in the neuropil of the optic lobe, within which there does not seem to be any preferential localization. These results emphasize the importance of the optic lobe in motor control.", "contents": "Motor and behavioral responses obtained by stimulation with chronic electrodes of the optic lobe of Sepia officinalis. A new technique using a stimulating chronically-implanted electrode has allowed us to study the motor responses induced by electrical stimulation of the optic lobe in a freely swimming Sepia. Electrical stimulation of the cortex of the optic lobe produces no motor response; this is in agreement with the results of preceding authors. The stimulation of the neuropil of the optic lobe by monopolar electrode produces many different motor responses, in support of Boycott's results obtained by the same type of excitation in acute experiments. However, the field of stimulation of these electrodes could not always have been the same and it is possible that we were sometimes stimulating nervous structures close to the optic lobe. Stimulation by a bipolar electrode, however, which does not have this advantage, induces only two very different motor responses: an ipsilateral rotation and an 'alarm reaction\", so called because of its similarities to the 'attentive immobilization\" of higher vertebrates. These two reactions are very complex and their different components are linked together as in a behavioural response from an intact animal. These reactions present very different characteristics of excitability. They are obtained from many areas in the neuropil of the optic lobe, within which there does not seem to be any preferential localization. These results emphasize the importance of the optic lobe in motor control."} {"id": "PMID:1260471", "title": "Using arousal changes in the EEG to indicate gustatory sensitivity following brain lesion in Gallus domesticus.", "content": "The EEG of Gallus domesticus was recorded before and after brain lesions following stimulation with light, sound and taste. 2. It was found that under the conditions of the experiment the lesions did not have any general effect on the arousal mechanism of the animal. 3. Bilateral lesions in the stratum cellulare externum of one animal had a specific effect on the arousal response to a quinine hydrochloride solution and it was concluded that it is possible to indicate deficits following brain lesion in the gustatory system using the EEG.", "contents": "Using arousal changes in the EEG to indicate gustatory sensitivity following brain lesion in Gallus domesticus. The EEG of Gallus domesticus was recorded before and after brain lesions following stimulation with light, sound and taste. 2. It was found that under the conditions of the experiment the lesions did not have any general effect on the arousal mechanism of the animal. 3. Bilateral lesions in the stratum cellulare externum of one animal had a specific effect on the arousal response to a quinine hydrochloride solution and it was concluded that it is possible to indicate deficits following brain lesion in the gustatory system using the EEG."} {"id": "PMID:1260472", "title": "Requirements of the young turkey for sulphur amino acids and threonine: comparison with other species.", "content": "1. The requirements of the 3-week-old turkey for the sulphur containing amino acids and for threonine were estimated to be 0.83% and 0.94% respectively in diets containing 12.5 MJ ME/kg. 2. It is suggested that the growth responses of rats and slow-growing chicks and of fast-growing chicks and young turkeys to daily intakes of the sulphur containing amino acids and of threonine are similar.", "contents": "Requirements of the young turkey for sulphur amino acids and threonine: comparison with other species. 1. The requirements of the 3-week-old turkey for the sulphur containing amino acids and for threonine were estimated to be 0.83% and 0.94% respectively in diets containing 12.5 MJ ME/kg. 2. It is suggested that the growth responses of rats and slow-growing chicks and of fast-growing chicks and young turkeys to daily intakes of the sulphur containing amino acids and of threonine are similar."} {"id": "PMID:1260473", "title": "The effects of progesterone on oviposition and ovulation in the domestic fowl (Gallus domesticus).", "content": "1. Following an injection of 0.5 or 0.1 mg progesterone/kg between 0 and 6 h after ovulation, oviposition of the resulting egg was delayed by 1 to 11 h and occurred 26 to 31 h after injection, depending on the dose. The injection terminated the laying of a sequence of eggs by causing the next ovulation to occur a day late. The delayed ovulation occurred at the time normally expected for the first ovulation a sequence and became the first of a new sequence. 2. Following an injection of 0.5 or 0.1 mg progesterone/kg between 6 and 15 h after ovulation, oviposition of the resulting egg was generally delayed by between 15 and 28 h and occurred at the same time of day as the next ovulation, which was delayed as in the first experimental situation. Subsequent ovulations were resynchronised and followed at intervals according to the normal sequence established before the injection. 3. Injection of 0.5, 0.1 or 0.05 mg progesterone/kg between 12 and 9 h before expected ovulation advanced the oviposition of the egg already in the uterus (shell gland) by about 3 h. The succeeding ovulation was either advanced or blocked. 4. These observations suggest that the pre-ovulatory surge of progesterone is directly or indirectly involved in the timing of oviposition and ovulation.", "contents": "The effects of progesterone on oviposition and ovulation in the domestic fowl (Gallus domesticus). 1. Following an injection of 0.5 or 0.1 mg progesterone/kg between 0 and 6 h after ovulation, oviposition of the resulting egg was delayed by 1 to 11 h and occurred 26 to 31 h after injection, depending on the dose. The injection terminated the laying of a sequence of eggs by causing the next ovulation to occur a day late. The delayed ovulation occurred at the time normally expected for the first ovulation a sequence and became the first of a new sequence. 2. Following an injection of 0.5 or 0.1 mg progesterone/kg between 6 and 15 h after ovulation, oviposition of the resulting egg was generally delayed by between 15 and 28 h and occurred at the same time of day as the next ovulation, which was delayed as in the first experimental situation. Subsequent ovulations were resynchronised and followed at intervals according to the normal sequence established before the injection. 3. Injection of 0.5, 0.1 or 0.05 mg progesterone/kg between 12 and 9 h before expected ovulation advanced the oviposition of the egg already in the uterus (shell gland) by about 3 h. The succeeding ovulation was either advanced or blocked. 4. These observations suggest that the pre-ovulatory surge of progesterone is directly or indirectly involved in the timing of oviposition and ovulation."} {"id": "PMID:1260474", "title": "The effect of continuous ultraviolet irradiation on broiler chickens.", "content": "1. Continuous ultraviolet irradiation (10.45 muW/cm2) did not affect the growth or food conversion efficiency of broilers. 2. The cornea of the eye was roughened by the treatment and there was a loss of the regular arrangement of the corneal cells: vision was not significantly affected after 49 d exposure.", "contents": "The effect of continuous ultraviolet irradiation on broiler chickens. 1. Continuous ultraviolet irradiation (10.45 muW/cm2) did not affect the growth or food conversion efficiency of broilers. 2. The cornea of the eye was roughened by the treatment and there was a loss of the regular arrangement of the corneal cells: vision was not significantly affected after 49 d exposure."} {"id": "PMID:1260475", "title": "Studies on the dilution of turkey semen.", "content": "1. A series of experiments were conducted to determine the effect of diluent, holding temperature and dilution rate on the viability of turkey semen. 2. No significant difference was observed in the fertility of the undiluted controls and semen diluted with Lake's solution to a final rate of 1:4 and maintained at 25 degrees C or 5 degrees C for 30 min. Under these conditions as few as 25 million sperm per weekly insemination were needed for optimum fertility. 3. Turkey semen exhibited the typical \"dilution effect\", increased respiration with a corresponding decline in fertilising capacity, when diluted at rates of 1 : 8 and 1 : 12.", "contents": "Studies on the dilution of turkey semen. 1. A series of experiments were conducted to determine the effect of diluent, holding temperature and dilution rate on the viability of turkey semen. 2. No significant difference was observed in the fertility of the undiluted controls and semen diluted with Lake's solution to a final rate of 1:4 and maintained at 25 degrees C or 5 degrees C for 30 min. Under these conditions as few as 25 million sperm per weekly insemination were needed for optimum fertility. 3. Turkey semen exhibited the typical \"dilution effect\", increased respiration with a corresponding decline in fertilising capacity, when diluted at rates of 1 : 8 and 1 : 12."} {"id": "PMID:1260476", "title": "Renal function changes in laying hens fed on dried poultry manure.", "content": "1. Renal function was studied in laying hens which had been fed on diets containing 0 (controls), 10 or 20% dried poultry manure (DPM) for one year. 2. Birds fed on 20% DPM showed increased rates of effective renal plasma flow and increased renal tubular secretion of urate during the infusion of large amounts of urate. 3. Renal hypertrophy was not detected in any group.", "contents": "Renal function changes in laying hens fed on dried poultry manure. 1. Renal function was studied in laying hens which had been fed on diets containing 0 (controls), 10 or 20% dried poultry manure (DPM) for one year. 2. Birds fed on 20% DPM showed increased rates of effective renal plasma flow and increased renal tubular secretion of urate during the infusion of large amounts of urate. 3. Renal hypertrophy was not detected in any group."} {"id": "PMID:1260477", "title": "Inbreeding components of body weight and growth rate in Japanese Quail.", "content": "1. The parental inbreeding component of body weight and daily gain was partitioned into paternal and maternal inbreeding components and the latter were found to be the mor important. 2. The contribution of the maternal inbreeding to the depression of characters was more pronounced on 1-d-old chicks, but declined as the chicks grew. 3. The body weight taken near sexual maturity showed a low and non-significant decline. 4. In spite of differences in the body weight of the two populations of Japanese quail the inbreeding components were similar.", "contents": "Inbreeding components of body weight and growth rate in Japanese Quail. 1. The parental inbreeding component of body weight and daily gain was partitioned into paternal and maternal inbreeding components and the latter were found to be the mor important. 2. The contribution of the maternal inbreeding to the depression of characters was more pronounced on 1-d-old chicks, but declined as the chicks grew. 3. The body weight taken near sexual maturity showed a low and non-significant decline. 4. In spite of differences in the body weight of the two populations of Japanese quail the inbreeding components were similar."} {"id": "PMID:1260478", "title": "Effect of dietary palmitic acid on broiler chicks fed on various concentrations of calcium.", "content": "1. The effect of dietary palmitic acid on body weight and bone-ash of chicks fed three concentrations of calcium was studied in a 2 X 3 factorial design (0 and 10% palmitic acid, 0.4, 0.7 and 1.0% calcium). 2. Body weight of chick not influenced by the calcium concentration when palmitic acid was not included in the diet. 3. When 10% palmitic acid was included the body weight of chicks fed 0.4 and 0.7% calcium was lower (P less than 0.01) than for the other groups. 4. Bone-ash was lower (P less than 0.01) for chicks fed 0.4% calcium than for the other two calcium concentrations when palmitic acid was not added and palmitic acid at 10% of the diet reduced bone-ash of the chicks fed 0.4 and 0.7% calcium (P less than 0.01).", "contents": "Effect of dietary palmitic acid on broiler chicks fed on various concentrations of calcium. 1. The effect of dietary palmitic acid on body weight and bone-ash of chicks fed three concentrations of calcium was studied in a 2 X 3 factorial design (0 and 10% palmitic acid, 0.4, 0.7 and 1.0% calcium). 2. Body weight of chick not influenced by the calcium concentration when palmitic acid was not included in the diet. 3. When 10% palmitic acid was included the body weight of chicks fed 0.4 and 0.7% calcium was lower (P less than 0.01) than for the other groups. 4. Bone-ash was lower (P less than 0.01) for chicks fed 0.4% calcium than for the other two calcium concentrations when palmitic acid was not added and palmitic acid at 10% of the diet reduced bone-ash of the chicks fed 0.4 and 0.7% calcium (P less than 0.01)."} {"id": "PMID:1260483", "title": "A new method for calculating the accretion rate of bone calcium and some observations on the suitability of strontium-85 as a tracer for bone calcium.", "content": "1. A new method for calculating the accretion rate (A) of bone calcium is proposed, based on an impulse analysis of 47Ca data. The method is free of most of the assumptions inherent in previous methods of analysis and appears to give more accurate estimates. 2. In fourteen normal subjects and twelve patients with metabolic bone disease, measurements of A by the new method gave very similar results to the mineralization rate calculated by the method of Burkinshaw et al. (1969). Analysis of twelve studies performed by Neer et al. (1967) gave good agreement with their five compartment model. A close relation between A and Marshall's (1964) A5 was observed, but the latter gave systematically higher results. 3. In sixteen studies both 47Ca and 85Sr were injected simultaneously. Although there were no systematic differences between the values of A for the two tracers, the differences between individual values were greater than the known experimental errors.", "contents": "A new method for calculating the accretion rate of bone calcium and some observations on the suitability of strontium-85 as a tracer for bone calcium. 1. A new method for calculating the accretion rate (A) of bone calcium is proposed, based on an impulse analysis of 47Ca data. The method is free of most of the assumptions inherent in previous methods of analysis and appears to give more accurate estimates. 2. In fourteen normal subjects and twelve patients with metabolic bone disease, measurements of A by the new method gave very similar results to the mineralization rate calculated by the method of Burkinshaw et al. (1969). Analysis of twelve studies performed by Neer et al. (1967) gave good agreement with their five compartment model. A close relation between A and Marshall's (1964) A5 was observed, but the latter gave systematically higher results. 3. In sixteen studies both 47Ca and 85Sr were injected simultaneously. Although there were no systematic differences between the values of A for the two tracers, the differences between individual values were greater than the known experimental errors."} {"id": "PMID:1260484", "title": "The blood: bone disequilibrium. I. The active accumulation of K+ into the bone extracellular fluid.", "content": "The role of periosteal and endosteal cellular envelopes in the control of the K+ and Na+ content of embryonic chick calvaria was investigated. Data have been presented which suggest that the K+ in extracellular fluid of calvaria may be under a direct membrane control similar to the pump-leak systems hypothesized for most cells. Based on DNA and K+ analysis of cell water, volume and DNA content, the K+ in the bone extracellular fluid was calculated to account for 75% of the total K+ content of intact calvaria. The bulk of K+ is therefore extracellular and its accumulation there was found to be sensitive to the presence of ouabain, iodoacetate, CCCP, and to temperature. Losses of 70% of calvaria K+ were found one hour after addition of 250 muM ouabain. If the exposure to ouabain was brief, the K+ loss was partially reversed. The rate of 42K+ uptake was found to be depressed by ouabain, decreased pH, and La2+. The total Na+ content of these calvaria was found not to vary when incubated with ouabain, iodoacetate, or CCCP.", "contents": "The blood: bone disequilibrium. I. The active accumulation of K+ into the bone extracellular fluid. The role of periosteal and endosteal cellular envelopes in the control of the K+ and Na+ content of embryonic chick calvaria was investigated. Data have been presented which suggest that the K+ in extracellular fluid of calvaria may be under a direct membrane control similar to the pump-leak systems hypothesized for most cells. Based on DNA and K+ analysis of cell water, volume and DNA content, the K+ in the bone extracellular fluid was calculated to account for 75% of the total K+ content of intact calvaria. The bulk of K+ is therefore extracellular and its accumulation there was found to be sensitive to the presence of ouabain, iodoacetate, CCCP, and to temperature. Losses of 70% of calvaria K+ were found one hour after addition of 250 muM ouabain. If the exposure to ouabain was brief, the K+ loss was partially reversed. The rate of 42K+ uptake was found to be depressed by ouabain, decreased pH, and La2+. The total Na+ content of these calvaria was found not to vary when incubated with ouabain, iodoacetate, or CCCP."} {"id": "PMID:1260485", "title": "The blood: bone disequilibrium. II. Evidence against the active accumulation of calcium or phosphate into the bone extracellular fluid.", "content": "An attempt was made to quantitate in vitro the unidirectional fluxes of Ca2+ and Pi across periosteal and endosteal membranes of frontal bones from calvaria of 20 day chick embryos. The influx of Ca2+, as previously reported, seemed to be passive [12]. The uncoupler, CCCP, had no effect on the influx of Ca2+, but increased both the endosteal and periosteal effluxes. La2+ decreased the influx of Ca2+. The influx of phosphate was also passive and proportional to the concentration of phosphate. The influx was unaffected by either iodoacetate or CCCP, but increased when the periosteal and endosteal membranes were removed; the efflux of phosphate was greater from the endosteal side and was unaffected by CCCP, while iodoacetate increased both the periosteal and endosteal effluxes. The evidence presented refutes the generally accepted hypothesis that Ca2+ (or phosphate) fluxes into and out of bone are governed by a pumpleak system. However, the increase in rate of influx when the cellular layers are removed indicates that the periosteum and endosteum constitute an important structural conponent in the maintenance of bone mineral and its equilibration with the circulation.", "contents": "The blood: bone disequilibrium. II. Evidence against the active accumulation of calcium or phosphate into the bone extracellular fluid. An attempt was made to quantitate in vitro the unidirectional fluxes of Ca2+ and Pi across periosteal and endosteal membranes of frontal bones from calvaria of 20 day chick embryos. The influx of Ca2+, as previously reported, seemed to be passive [12]. The uncoupler, CCCP, had no effect on the influx of Ca2+, but increased both the endosteal and periosteal effluxes. La2+ decreased the influx of Ca2+. The influx of phosphate was also passive and proportional to the concentration of phosphate. The influx was unaffected by either iodoacetate or CCCP, but increased when the periosteal and endosteal membranes were removed; the efflux of phosphate was greater from the endosteal side and was unaffected by CCCP, while iodoacetate increased both the periosteal and endosteal effluxes. The evidence presented refutes the generally accepted hypothesis that Ca2+ (or phosphate) fluxes into and out of bone are governed by a pumpleak system. However, the increase in rate of influx when the cellular layers are removed indicates that the periosteum and endosteum constitute an important structural conponent in the maintenance of bone mineral and its equilibration with the circulation."} {"id": "PMID:1260486", "title": "Effects of calcitonin and ultimobranchialectomy (UBX) on calcium and bone metabolism in the eel, Anguilla anguilla L.", "content": "Prolonged administration of synthetic salmon calcitonin (SCT) to immature female silver eels, maintained in sea water, provoked a decrease of the serum calcium concentration and an increase of both the osteoblastic apposition and of the degree of mineralization of the intercellular matrix in the vertebral bone. The osteoclastic resorption and osteocytic osteolysis were not significantly affected, however the osteoclastic index was reduced. The ultimobranchial body, site of CT secretion, was cauterized in immature female silver eels maintained in Ca++ rich tap water. This operation resulted in a rise in serum calcium levels with a maximal response after two weeks. After UBX, the vertebral bone osteoblastic apposition stopped completely but the osteoclastic resorption was not modified. The degree of osteocytic osteolysis did not vary. We also observed a significant decrease in the degree of mineralization of the bone organic matrix. The observations made after UBX confirm those obtained after exogenous CT treatment. SCT administered preventively to immature female eels (maintained in sea water), before experimental maturation, inhibited, at least partially, the acute osteoclastic resorption and completely inhibited the bone demineralization induced by carp pituitary extract. The increase of osteocytic ostelysis, usually observed, did not appear.", "contents": "Effects of calcitonin and ultimobranchialectomy (UBX) on calcium and bone metabolism in the eel, Anguilla anguilla L. Prolonged administration of synthetic salmon calcitonin (SCT) to immature female silver eels, maintained in sea water, provoked a decrease of the serum calcium concentration and an increase of both the osteoblastic apposition and of the degree of mineralization of the intercellular matrix in the vertebral bone. The osteoclastic resorption and osteocytic osteolysis were not significantly affected, however the osteoclastic index was reduced. The ultimobranchial body, site of CT secretion, was cauterized in immature female silver eels maintained in Ca++ rich tap water. This operation resulted in a rise in serum calcium levels with a maximal response after two weeks. After UBX, the vertebral bone osteoblastic apposition stopped completely but the osteoclastic resorption was not modified. The degree of osteocytic osteolysis did not vary. We also observed a significant decrease in the degree of mineralization of the bone organic matrix. The observations made after UBX confirm those obtained after exogenous CT treatment. SCT administered preventively to immature female eels (maintained in sea water), before experimental maturation, inhibited, at least partially, the acute osteoclastic resorption and completely inhibited the bone demineralization induced by carp pituitary extract. The increase of osteocytic ostelysis, usually observed, did not appear."} {"id": "PMID:1260487", "title": "The total luminescence of bovine and human dental enamel.", "content": "The corrected emission and excitation spectra of human and bovine dental enamel and its separated organic material were determined at room temperature and liquid nitrogen temperature. In both materials three distinct luminescence peaks were found in the region 350-360 nm, 405-410 nm, 440-450 nm. The intensity ratios of the peaks of the enamel do not differ substantially upon removal of the inorganic component. Hence a conclusion is confirmed that the organic component is the most responsible material for the total luminescence of the enamel. Several hypothesis are available for determination of the nature of luminescence of the organic components. Differences in the excitation spectra are discussed. Phosphorescence emission and phosphorescence lifetimes were determined.", "contents": "The total luminescence of bovine and human dental enamel. The corrected emission and excitation spectra of human and bovine dental enamel and its separated organic material were determined at room temperature and liquid nitrogen temperature. In both materials three distinct luminescence peaks were found in the region 350-360 nm, 405-410 nm, 440-450 nm. The intensity ratios of the peaks of the enamel do not differ substantially upon removal of the inorganic component. Hence a conclusion is confirmed that the organic component is the most responsible material for the total luminescence of the enamel. Several hypothesis are available for determination of the nature of luminescence of the organic components. Differences in the excitation spectra are discussed. Phosphorescence emission and phosphorescence lifetimes were determined."} {"id": "PMID:1260488", "title": "Comparison of whole calvarial bones and long bones during early growth in rats. II. Turnover of calcified and uncalcified collagen masses.", "content": "The increase of total collagen and its destruction were compared for whole calvaria and long bones from young growing rats prelabeled in utero with 3H-L-proline. Rats were compared from birth to 16 weeks of age. Long bones and calvaria were isolated as intact anatomical units for autoradiography or separated by collagenase into calified and uncalcified collagens. Autoradiography using 14C-L-proline demonstrated eccentric modeling of bone collagen. With growth the mass of calcified collagen (bone) increased rapidly in calvaria and long bones. A similar increase in the mass of uncalcified collagen (mainly cartilage) occured in the long bones; a very small increase occurred in the fibrous tissue of calvaria. Total and specific radioactivities of collagens at each age were compared to that present at birth. With growth remodeling an almost complete loss of pre-existing radioactive collagen occurred from uncalcified fibrous tissue of calvaria as compared to a smaller but substantial loss from the uncalcified cartilage of long bones. A marked loss of calcifed collagen occurred in long bones as compared to a smaller loss from calvarial bones. The istopic data indicate a large turnover of fibrous tissue (type I collagen) with growth remodeling as compared to a smaller turnover of bone (calcified, type I collagen) and cartilage (typc I collagen). The turnover rate of skeletal collagens depends upon whether the collagen is calcified or not, and not upon the type of collagen.", "contents": "Comparison of whole calvarial bones and long bones during early growth in rats. II. Turnover of calcified and uncalcified collagen masses. The increase of total collagen and its destruction were compared for whole calvaria and long bones from young growing rats prelabeled in utero with 3H-L-proline. Rats were compared from birth to 16 weeks of age. Long bones and calvaria were isolated as intact anatomical units for autoradiography or separated by collagenase into calified and uncalcified collagens. Autoradiography using 14C-L-proline demonstrated eccentric modeling of bone collagen. With growth the mass of calcified collagen (bone) increased rapidly in calvaria and long bones. A similar increase in the mass of uncalcified collagen (mainly cartilage) occured in the long bones; a very small increase occurred in the fibrous tissue of calvaria. Total and specific radioactivities of collagens at each age were compared to that present at birth. With growth remodeling an almost complete loss of pre-existing radioactive collagen occurred from uncalcified fibrous tissue of calvaria as compared to a smaller but substantial loss from the uncalcified cartilage of long bones. A marked loss of calcifed collagen occurred in long bones as compared to a smaller loss from calvarial bones. The istopic data indicate a large turnover of fibrous tissue (type I collagen) with growth remodeling as compared to a smaller turnover of bone (calcified, type I collagen) and cartilage (typc I collagen). The turnover rate of skeletal collagens depends upon whether the collagen is calcified or not, and not upon the type of collagen."} {"id": "PMID:1260489", "title": "Concurrent exchange of 45Ca and 3H-tetracycline from rat bone in vitro.", "content": "Bone from rats sacrified at 2, 5, and 95 weeks of age following 45Ca and 3H-tetracycline labeling in utero or postnatally was placed in solutions of physiological saline, nonradioactive calcium, or tetracycline. This procedure was designed to determine the availability for exchange of 45Ca and 3H-tetracycline from bone mineral in vitro. With time after labeling a gradual decrease occurred in both the nonspecific loss and specific exchange of 45Ca and 3H-tetracycline. 45Ca and 3H-tetracycline in bone could be partially exchanged in vitro with their respective nonradioactive counterparts. Each isotope could be partially exchanged, independently of the other istope. Nonradioactive calcium increased the exchange of 45Ca while suppressing the release of 3H-tetracycline. Molecular 3H-tetracycline exchange occurred to a greater degree than ionic 45Ca exchange and was associated with a small loss of 45Ca. The molecular exchange of 3H-tetracycline with bulk tetracycline did not induce any significant loss of tritium from 3H-tetracycline.", "contents": "Concurrent exchange of 45Ca and 3H-tetracycline from rat bone in vitro. Bone from rats sacrified at 2, 5, and 95 weeks of age following 45Ca and 3H-tetracycline labeling in utero or postnatally was placed in solutions of physiological saline, nonradioactive calcium, or tetracycline. This procedure was designed to determine the availability for exchange of 45Ca and 3H-tetracycline from bone mineral in vitro. With time after labeling a gradual decrease occurred in both the nonspecific loss and specific exchange of 45Ca and 3H-tetracycline. 45Ca and 3H-tetracycline in bone could be partially exchanged in vitro with their respective nonradioactive counterparts. Each isotope could be partially exchanged, independently of the other istope. Nonradioactive calcium increased the exchange of 45Ca while suppressing the release of 3H-tetracycline. Molecular 3H-tetracycline exchange occurred to a greater degree than ionic 45Ca exchange and was associated with a small loss of 45Ca. The molecular exchange of 3H-tetracycline with bulk tetracycline did not induce any significant loss of tritium from 3H-tetracycline."} {"id": "PMID:1260490", "title": "Factors affecting the distribution of zinc in the human skeleton.", "content": "The zinc content of trabecular and cortical bone was measured in 28 femora obtained at autopsy. The ratios of calcium to zinc, phosphorus and magnesium were determined and their relation to age and vertebral density was investigated. The calcium/zinc ration was significantly higher in cortical as opposed to trabecular bone, whereas the calcium/phosphorus ratios were similar. There was a significant decrease in the calcium/zinc ratios of both trabecular and cortical bone with age and the former was directly related to vertebral density. The calcium/phosphorus ratios of trabecular and cortical bone did not vary significantly with age or vertebral density. Magnesium/zinc ratios tended to parallel the calcium/zinc ratios. The calcium/magnesium ratios were significantly higher in cortical as opposed to trabecular bone. None of these ratios appeared to be affected by the sex of the subject. These findings suggest that changes in skeletal zinc content with age are related to alterations in bone morphology, and that osteoporosis in man develops in association with zinc accumulation rather than zinc deficiency.", "contents": "Factors affecting the distribution of zinc in the human skeleton. The zinc content of trabecular and cortical bone was measured in 28 femora obtained at autopsy. The ratios of calcium to zinc, phosphorus and magnesium were determined and their relation to age and vertebral density was investigated. The calcium/zinc ration was significantly higher in cortical as opposed to trabecular bone, whereas the calcium/phosphorus ratios were similar. There was a significant decrease in the calcium/zinc ratios of both trabecular and cortical bone with age and the former was directly related to vertebral density. The calcium/phosphorus ratios of trabecular and cortical bone did not vary significantly with age or vertebral density. Magnesium/zinc ratios tended to parallel the calcium/zinc ratios. The calcium/magnesium ratios were significantly higher in cortical as opposed to trabecular bone. None of these ratios appeared to be affected by the sex of the subject. These findings suggest that changes in skeletal zinc content with age are related to alterations in bone morphology, and that osteoporosis in man develops in association with zinc accumulation rather than zinc deficiency."} {"id": "PMID:1260491", "title": "The capacity of pig articular cartilage in organ culture to regenerate after breakdown induced by complement-sufficient antiserum to pig erythrocytes.", "content": "Explants of pig articular cartilage including invading marrow and subchondral bone (together='invasion zone') were cultivated for 10 or 14 days in complement-sufficient rabbit antiserum to pig erythrocytes (AS+C'), and then transferred to heat-inactivated normal rabbit serum (NRS) for a period of recovery. In AS+C' the cartilage matrix lost first proteoglycan and then collagen, but the cells remained viable. The degradation of collagen was accompanied by a fibroblastic transformation of the chodrocytes, first seen in the region immediately above the invasion zone. Immunohistochemical studies showed that after cultivation in AS+C', IgG antibodies entered areas in which the matrix was depleted of proteoglycan and reacted strongly with the majority of chondrocytes; those that had under-gone fibroblastic transformation exhibited little or no reaction. The degree of recovery in NRS depended on the extent to which the matrix had broken down in AS+C'. If degradation of collagen was confined to the region immediately above the invasion zone, and elsewhere only proteoglycan had been lost, new metachromatic material was regenerated in the non-calcified cartilage, and the fibroblast-like chondrocytes resumed their normal appearance and regained their reactivity with the IgG antibodies of AS; new cartilage and chondroid tissue appeared in the cavities of the invasion zone. If degradation of collagen and fibroblastic transformation of chondrocytes had spread throughout the cartilage, breakdown continued in NRS and cartilage disappeared completely above the invasion zone; new cartilage waw sometimes formed in the cavities of the invasione zone.", "contents": "The capacity of pig articular cartilage in organ culture to regenerate after breakdown induced by complement-sufficient antiserum to pig erythrocytes. Explants of pig articular cartilage including invading marrow and subchondral bone (together='invasion zone') were cultivated for 10 or 14 days in complement-sufficient rabbit antiserum to pig erythrocytes (AS+C'), and then transferred to heat-inactivated normal rabbit serum (NRS) for a period of recovery. In AS+C' the cartilage matrix lost first proteoglycan and then collagen, but the cells remained viable. The degradation of collagen was accompanied by a fibroblastic transformation of the chodrocytes, first seen in the region immediately above the invasion zone. Immunohistochemical studies showed that after cultivation in AS+C', IgG antibodies entered areas in which the matrix was depleted of proteoglycan and reacted strongly with the majority of chondrocytes; those that had under-gone fibroblastic transformation exhibited little or no reaction. The degree of recovery in NRS depended on the extent to which the matrix had broken down in AS+C'. If degradation of collagen was confined to the region immediately above the invasion zone, and elsewhere only proteoglycan had been lost, new metachromatic material was regenerated in the non-calcified cartilage, and the fibroblast-like chondrocytes resumed their normal appearance and regained their reactivity with the IgG antibodies of AS; new cartilage and chondroid tissue appeared in the cavities of the invasion zone. If degradation of collagen and fibroblastic transformation of chondrocytes had spread throughout the cartilage, breakdown continued in NRS and cartilage disappeared completely above the invasion zone; new cartilage waw sometimes formed in the cavities of the invasione zone."} {"id": "PMID:1260492", "title": "The distribution of cortical and trabecular bone mass along the lengths of the radius and ulna and the implications for in vivo bone mass measurements.", "content": "The amounts of cortical and trabecular bone mineral mass were measured by means of microdissection and an ashing technique at approximately 2.5 mm intervals along the most distal 12 cm of radii and ulnae from four women aged 21, 43, 63, and 85. The data show that the distributions of mineral mass and percentage of trabecular bone are similar in both bones. At sites in the radius and ulna commonly used in the photon absorptiometric method of bone mineral mass measurement the percentage of trabecular bone varies between 10% and 50%. The percentage of trabecular bone in the most distal 10% of the length of the radius and ulna remains approximately constant with age but the percentage in the segment which lies between 30% and 40% of the length, measured from the styloid process, increases with age.", "contents": "The distribution of cortical and trabecular bone mass along the lengths of the radius and ulna and the implications for in vivo bone mass measurements. The amounts of cortical and trabecular bone mineral mass were measured by means of microdissection and an ashing technique at approximately 2.5 mm intervals along the most distal 12 cm of radii and ulnae from four women aged 21, 43, 63, and 85. The data show that the distributions of mineral mass and percentage of trabecular bone are similar in both bones. At sites in the radius and ulna commonly used in the photon absorptiometric method of bone mineral mass measurement the percentage of trabecular bone varies between 10% and 50%. The percentage of trabecular bone in the most distal 10% of the length of the radius and ulna remains approximately constant with age but the percentage in the segment which lies between 30% and 40% of the length, measured from the styloid process, increases with age."} {"id": "PMID:1260493", "title": "The alteration of osteoclast morphology by diphosphonates in bone organ culture.", "content": "Two diphosphonates alter the morphology of the osteoclast, as they inhibit the calcium45 release from bones stimulated to resorb by lipopolysaccharide. Disodium dichloromethylene diphosphonate was more potent than disodium ethane-1-hydroxy-1, 1-diphosphonate in both inhibiting 45calium release and altering osteoclast morphology. Alteration in the morphology of osteoclasts is associated with little or no change in the morphology of the surrounding non-osteoclast cells. These results indicate a specific morphological effect of diphosphonates on osteoclasts.", "contents": "The alteration of osteoclast morphology by diphosphonates in bone organ culture. Two diphosphonates alter the morphology of the osteoclast, as they inhibit the calcium45 release from bones stimulated to resorb by lipopolysaccharide. Disodium dichloromethylene diphosphonate was more potent than disodium ethane-1-hydroxy-1, 1-diphosphonate in both inhibiting 45calium release and altering osteoclast morphology. Alteration in the morphology of osteoclasts is associated with little or no change in the morphology of the surrounding non-osteoclast cells. These results indicate a specific morphological effect of diphosphonates on osteoclasts."} {"id": "PMID:1260494", "title": "Rib structure and bending strength: an autopsy study.", "content": "Mechanical rib testing and geometric analysis were explored as means of evaluating metabolic bone disease. Seventy-nine male patients were examined postmortem. Displacement rate at the loading point and patient age were important variables for which results had to be corrected. Like long bones, ribs apparently undergo progressive circumendosteal resorption with advancing age but unlike long bones, they show no evidence of continued subperiosteal apposition. Effects of selected individual diseases and of all diseases grouped by major organ system were analyzed. Most produced no discernible modification of rib volume, geometry or bending strength as quantified by modulus of rupture. Exceptions were myeloma and arthritis, where the bony material was weakened without remodeling or loss in volume.", "contents": "Rib structure and bending strength: an autopsy study. Mechanical rib testing and geometric analysis were explored as means of evaluating metabolic bone disease. Seventy-nine male patients were examined postmortem. Displacement rate at the loading point and patient age were important variables for which results had to be corrected. Like long bones, ribs apparently undergo progressive circumendosteal resorption with advancing age but unlike long bones, they show no evidence of continued subperiosteal apposition. Effects of selected individual diseases and of all diseases grouped by major organ system were analyzed. Most produced no discernible modification of rib volume, geometry or bending strength as quantified by modulus of rupture. Exceptions were myeloma and arthritis, where the bony material was weakened without remodeling or loss in volume."} {"id": "PMID:1260495", "title": "The interaction of supersaturated calcium phosphate solutions with apatitic substrates.", "content": "The in vitro formation of calcium phosphates from supersaturated solutions seeded with apatite was examined. Reaction kinetics were followed by monitoring solution Ca, Mg, and PO4. Seeds and reaction products were examined chemically and by X-ray diffraction and electron microscopy. Under conditions where amorphous calcium phosphate (ACP) normally precipitates spontaneously, apatite reduced the amount of free ACP formed with a considerable fraction of the Ca and PO4 initially removed from solution depositing directly onto the seeds. At sufficiently great seed concentrations all initial solution losses occurred by this latter route with no free ACP precipitating. These initial events were followed by seed-induced formation of new apatite crystals accompanied by further losses in solution Ca and PO4. Supersaturated solutions stable to spontaneous ACP formation underwent similar losses in solution Ca and PO4 when seeded with apatite. Initial decrease in these ions was instantaneous and proportional to the seed concentration. Subsequent ion removal exponentially decreased with time and correlated with the formation of new apatite crystals overlaying the original seeds. In seeding experiments using physiologically-balanced salt solutions, the initial deposit formed on the seed surface was a magnesium stabilized calcium carbonate phosphate phase. This stable surface phase did not prevent the secondary crystallization of apatite from occurring.", "contents": "The interaction of supersaturated calcium phosphate solutions with apatitic substrates. The in vitro formation of calcium phosphates from supersaturated solutions seeded with apatite was examined. Reaction kinetics were followed by monitoring solution Ca, Mg, and PO4. Seeds and reaction products were examined chemically and by X-ray diffraction and electron microscopy. Under conditions where amorphous calcium phosphate (ACP) normally precipitates spontaneously, apatite reduced the amount of free ACP formed with a considerable fraction of the Ca and PO4 initially removed from solution depositing directly onto the seeds. At sufficiently great seed concentrations all initial solution losses occurred by this latter route with no free ACP precipitating. These initial events were followed by seed-induced formation of new apatite crystals accompanied by further losses in solution Ca and PO4. Supersaturated solutions stable to spontaneous ACP formation underwent similar losses in solution Ca and PO4 when seeded with apatite. Initial decrease in these ions was instantaneous and proportional to the seed concentration. Subsequent ion removal exponentially decreased with time and correlated with the formation of new apatite crystals overlaying the original seeds. In seeding experiments using physiologically-balanced salt solutions, the initial deposit formed on the seed surface was a magnesium stabilized calcium carbonate phosphate phase. This stable surface phase did not prevent the secondary crystallization of apatite from occurring."} {"id": "PMID:1260496", "title": "Biosynthesis of diacylglycerols by rat intestinal mucosa in vivo.", "content": "The biosynthesis of diacylglycerols was studied in rat intestinal mucosa during in vivo absorption of a low molecular weight fraction fraction of butter oil and of the corresponding medium and long chain fatty acids. The experimental fat solutions were given by stomach tube to the animals after a 24-h fast and mucosal scraping were collected 3 h later. The lipids were isolated and the acylclycerols determined by combined thin-layer chromatography gas-liquid chromatography techniques and stereospecific analyses. Free fatty acid feeding led mainly to sn-1,2-diacyl-glycerols, which contained exogenous and endogenous fatty acids. During triacylglycerol feeding, both sn-1,2-and sn-2,3-diacylglycerols were recovered in significant amounts from the intestinal mucosa. The composition of the sn-2,3-diacylglycerols corresponded to that with exogenous fatty acids but the sn-1,2-diacylglycerols clearly contained both exogenous and endogenous fatty acids. In all cases it was possible to isolate endogenous sn-1,2-diacylglycerols made up largely of species with linoleic and arachidonic acids in the 2 position and palmitic and stearic acids in the 1 position, which apparently were not converted to triacylglycerols. The in vivo reacylation of 2-monoacylglycerols via both sn-1,2- and sn-2,3-diacylglycerols is in agreement with similar findings in vitro with everted sacs of rat intestinal mucosa.", "contents": "Biosynthesis of diacylglycerols by rat intestinal mucosa in vivo. The biosynthesis of diacylglycerols was studied in rat intestinal mucosa during in vivo absorption of a low molecular weight fraction fraction of butter oil and of the corresponding medium and long chain fatty acids. The experimental fat solutions were given by stomach tube to the animals after a 24-h fast and mucosal scraping were collected 3 h later. The lipids were isolated and the acylclycerols determined by combined thin-layer chromatography gas-liquid chromatography techniques and stereospecific analyses. Free fatty acid feeding led mainly to sn-1,2-diacyl-glycerols, which contained exogenous and endogenous fatty acids. During triacylglycerol feeding, both sn-1,2-and sn-2,3-diacylglycerols were recovered in significant amounts from the intestinal mucosa. The composition of the sn-2,3-diacylglycerols corresponded to that with exogenous fatty acids but the sn-1,2-diacylglycerols clearly contained both exogenous and endogenous fatty acids. In all cases it was possible to isolate endogenous sn-1,2-diacylglycerols made up largely of species with linoleic and arachidonic acids in the 2 position and palmitic and stearic acids in the 1 position, which apparently were not converted to triacylglycerols. The in vivo reacylation of 2-monoacylglycerols via both sn-1,2- and sn-2,3-diacylglycerols is in agreement with similar findings in vitro with everted sacs of rat intestinal mucosa."} {"id": "PMID:1260497", "title": "Biosynthesis of triacylglycerols by rat intestinal mucosa in vivo.", "content": "The structure of mucosal triacylglycerols was studied in rat intestinal mucosa in vivo during the absorption of a low molecular weight fraction of butter oil and of the corresponding free fatty acids of medium and long chain length. The mucosal lipids were isolated by solvent extraction and the acylglycerol structures were determined by combined AgNO3- thin-layer chromatography and gas-liquid chromatography techniques and stereospecific analysis. Evidence was obtained for a rapid biosynthesis of triacylglycerols from diacylglycerols arising from the operation of both the monoacylglycerol and the phosphatidic acid biosynthetic pathways. Both sn-1,2- and sn-2,3-diacylglycerols appeared to be converted to triacylglycerols at significant rates, but a preferential utilization of sn-1,2-diacylglycerols could not be excluded. Endogenous dilution varied from a miniumum of 5% during triacylglycerol biosynthesis from monoacylglycerols to 15% during their synthesis from free fatty acids, and was characterized by a preferential placement of the endogenous acids in the sn-3 and 2 positions of the triacylglycerol molecules. Exogenous myristic acid was preferentially associated with the sn-3 position, and stearic acid became preferentially bound to the sn-1 position. The complexity of the triacylglycerol end products prevented an exact estimate of the contribution of the phosphatidic acid pathway, but the acylglycerol structures were compatible with a minimum of 20% of total triacylglycerol yield at all times.", "contents": "Biosynthesis of triacylglycerols by rat intestinal mucosa in vivo. The structure of mucosal triacylglycerols was studied in rat intestinal mucosa in vivo during the absorption of a low molecular weight fraction of butter oil and of the corresponding free fatty acids of medium and long chain length. The mucosal lipids were isolated by solvent extraction and the acylglycerol structures were determined by combined AgNO3- thin-layer chromatography and gas-liquid chromatography techniques and stereospecific analysis. Evidence was obtained for a rapid biosynthesis of triacylglycerols from diacylglycerols arising from the operation of both the monoacylglycerol and the phosphatidic acid biosynthetic pathways. Both sn-1,2- and sn-2,3-diacylglycerols appeared to be converted to triacylglycerols at significant rates, but a preferential utilization of sn-1,2-diacylglycerols could not be excluded. Endogenous dilution varied from a miniumum of 5% during triacylglycerol biosynthesis from monoacylglycerols to 15% during their synthesis from free fatty acids, and was characterized by a preferential placement of the endogenous acids in the sn-3 and 2 positions of the triacylglycerol molecules. Exogenous myristic acid was preferentially associated with the sn-3 position, and stearic acid became preferentially bound to the sn-1 position. The complexity of the triacylglycerol end products prevented an exact estimate of the contribution of the phosphatidic acid pathway, but the acylglycerol structures were compatible with a minimum of 20% of total triacylglycerol yield at all times."} {"id": "PMID:1260498", "title": "Mitochondria with impaired phosphate transport: 32P uptake studies.", "content": "Rat liver mitochondria which have been exposed to 0.15 M NaC1 at 35 degrees C for 15 min subsequently take up 32Pi from an external medium only to about 5% of the extent of uptake by control mitochondria. The volume into which 32Pi distributes in a pellet of such \"aged\" mitochondia is less than that available to 3H2O but is greater than that available to [3H]sucrose. Mitochondria treated in this manner cannot therefore accumulate Pi although limited penetration of the inner membrane can occur. These results confirm earlier findings by indirect methods (Williams, G. R. & Orr, J. L.: Dynamics of energy-transducing membranes (Ernster, L., Estabrook, R. W. & Slater, E. C., eds), Elsevier Scientific Publishing Company, Amsterdam, Netherlands, pp. 497-508 (1974).", "contents": "Mitochondria with impaired phosphate transport: 32P uptake studies. Rat liver mitochondria which have been exposed to 0.15 M NaC1 at 35 degrees C for 15 min subsequently take up 32Pi from an external medium only to about 5% of the extent of uptake by control mitochondria. The volume into which 32Pi distributes in a pellet of such \"aged\" mitochondia is less than that available to 3H2O but is greater than that available to [3H]sucrose. Mitochondria treated in this manner cannot therefore accumulate Pi although limited penetration of the inner membrane can occur. These results confirm earlier findings by indirect methods (Williams, G. R. & Orr, J. L.: Dynamics of energy-transducing membranes (Ernster, L., Estabrook, R. W. & Slater, E. C., eds), Elsevier Scientific Publishing Company, Amsterdam, Netherlands, pp. 497-508 (1974)."} {"id": "PMID:1260499", "title": "Effect of palmitoyl-CoA and beta-oxidation of fatty acids on the kinetics of mitochondrial citrate transporter.", "content": "The kinetics of the hepatic mitochondrial citrate transporter were studied using 1,2,3-benzene tricarboxylate and the inhibitor-stop technique at 8 degrees C. The apparent Km for this transporter was 250 muM and the maximum velocity was 2 nmol of citrate transported per minute per milligram of mitochondrial protein. This apparent Km was increased when hepatic mitochondria were preincubated with both L-palmitoylcarnitine and CoA-SH but not with either alone. This rise in apparent Km was accompanied by a rise in the acid insoluble CoA-SH content. Removal of mitochondrial acid insoluble CoA by \"defatted albumin\" resulted in a parallel decrease in the apparent Km. The apparent Km for the citrate transporter was increased after coupled beta-oxidation of L-palmitoylcarnitine or octanoate without a detectable increase in acid insoluble CoA. Inhibition of beta-oxidation of L-palmitoylcarnitine by the D-derivative prevented the rise in the apparent Km. Preincubation with ATP resulted in an increase in this apparent Km. When L-palmitoylcarnitine oxidation occurred without ATP accumulation (hexokinase, glucose, ADP, and inorganic phosphate) the apparent Km for the citrate transporter increased two- to threefold. Therefore, the apparent Km for the citrate transporter varied directly with the acid insoluble CoA content. In addition, this Km was increased as a result of beta-oxidation of fatty acids but the mechanism was not solely attributable to a rise in acid insoluble CoA or ATP. The physiological implications of these findings are discussed.", "contents": "Effect of palmitoyl-CoA and beta-oxidation of fatty acids on the kinetics of mitochondrial citrate transporter. The kinetics of the hepatic mitochondrial citrate transporter were studied using 1,2,3-benzene tricarboxylate and the inhibitor-stop technique at 8 degrees C. The apparent Km for this transporter was 250 muM and the maximum velocity was 2 nmol of citrate transported per minute per milligram of mitochondrial protein. This apparent Km was increased when hepatic mitochondria were preincubated with both L-palmitoylcarnitine and CoA-SH but not with either alone. This rise in apparent Km was accompanied by a rise in the acid insoluble CoA-SH content. Removal of mitochondrial acid insoluble CoA by \"defatted albumin\" resulted in a parallel decrease in the apparent Km. The apparent Km for the citrate transporter was increased after coupled beta-oxidation of L-palmitoylcarnitine or octanoate without a detectable increase in acid insoluble CoA. Inhibition of beta-oxidation of L-palmitoylcarnitine by the D-derivative prevented the rise in the apparent Km. Preincubation with ATP resulted in an increase in this apparent Km. When L-palmitoylcarnitine oxidation occurred without ATP accumulation (hexokinase, glucose, ADP, and inorganic phosphate) the apparent Km for the citrate transporter increased two- to threefold. Therefore, the apparent Km for the citrate transporter varied directly with the acid insoluble CoA content. In addition, this Km was increased as a result of beta-oxidation of fatty acids but the mechanism was not solely attributable to a rise in acid insoluble CoA or ATP. The physiological implications of these findings are discussed."} {"id": "PMID:1260500", "title": "Pyrimidine reducing enzymes of rat liver.", "content": "Dihydrouracil dehydrogenase (NADP+) (EC 1.3.1.2) was partially purified from the cytosol fraction of rat liver and fractionated by disc gel electrophoresis. A major and minor band were visualized by staining for enzyme activity. The substrate specificity of these bands was investigated. It was found that both bands were two to three times more active with dihydrothymine as substrate than with dihydrouracil in the presence of NADP+ and the optimum pH of 7.4. Mitochondrial fractions containing most of the NADH-dependent uracil reductase of rat liver cells were fractionated by centrifugation in sucrose density gradients. Two procedures involving linear or discontinuous gradients were used. By both, good separation of NADH- and NADPH- dependent reductases was achieved. Marker enzyme studies supported the view that the NADH-dependent enzyme is located principally in mitochondria whereas the NADPH-dependent enzyme is mainly in plasma and endoplasmic reticulum membranes. For the NADH-dependent reductase the apparent Km for thymine at pH 7.4 was 1.39 times that found for uracil whereas for the NADPH-dependent enzyme the apparent Km values were similar for the two substrates at this pH. Dihydrouracil was the principal product isolated by paper chromatography from the reaction mixture containing a partially purified fraction of mitochondria, uracil and NADH at pH 7.4. This fraction also catalyzed the formation of radioactive carbon dioxide from [2-14C]uracil. The proportion of CO2 formed by the mitochondria was about 10% of that formed by the original homogenate.", "contents": "Pyrimidine reducing enzymes of rat liver. Dihydrouracil dehydrogenase (NADP+) (EC 1.3.1.2) was partially purified from the cytosol fraction of rat liver and fractionated by disc gel electrophoresis. A major and minor band were visualized by staining for enzyme activity. The substrate specificity of these bands was investigated. It was found that both bands were two to three times more active with dihydrothymine as substrate than with dihydrouracil in the presence of NADP+ and the optimum pH of 7.4. Mitochondrial fractions containing most of the NADH-dependent uracil reductase of rat liver cells were fractionated by centrifugation in sucrose density gradients. Two procedures involving linear or discontinuous gradients were used. By both, good separation of NADH- and NADPH- dependent reductases was achieved. Marker enzyme studies supported the view that the NADH-dependent enzyme is located principally in mitochondria whereas the NADPH-dependent enzyme is mainly in plasma and endoplasmic reticulum membranes. For the NADH-dependent reductase the apparent Km for thymine at pH 7.4 was 1.39 times that found for uracil whereas for the NADPH-dependent enzyme the apparent Km values were similar for the two substrates at this pH. Dihydrouracil was the principal product isolated by paper chromatography from the reaction mixture containing a partially purified fraction of mitochondria, uracil and NADH at pH 7.4. This fraction also catalyzed the formation of radioactive carbon dioxide from [2-14C]uracil. The proportion of CO2 formed by the mitochondria was about 10% of that formed by the original homogenate."} {"id": "PMID:1260501", "title": "The specific activity of aldolase in the livers of old and young rats.", "content": "The catalytic activity of liver fructose-biphosphate aldolase (EC 4.1.2.13) of young and old rats in units per manomole sequence has been calculated. No evidence of the accumulation with age of altered enzyme molecules of low catalytic activity was obtained. This is contrary to results obtained using mice and rabbits and indicates that the accumulation of altered enzymes may not always be associated with aging. The possibility that altered proteins are formed, but do not accumulate, cannot be ruled out.", "contents": "The specific activity of aldolase in the livers of old and young rats. The catalytic activity of liver fructose-biphosphate aldolase (EC 4.1.2.13) of young and old rats in units per manomole sequence has been calculated. No evidence of the accumulation with age of altered enzyme molecules of low catalytic activity was obtained. This is contrary to results obtained using mice and rabbits and indicates that the accumulation of altered enzymes may not always be associated with aging. The possibility that altered proteins are formed, but do not accumulate, cannot be ruled out."} {"id": "PMID:1260502", "title": "Molecular weight of an extremely hydrophobic protein, zein, in dimethylformamide and in formamide.", "content": "Both alpha zein purified from a commericial preparation and beta zein prepared fresh from corn are soluble in the nonaqueous solvents formamide and dimethylformamide; in this regard zein resembles water soluble proteins such as insulin, ribonuclease, and lysozyme. On the basis of osmotic pressure measurements made in both formamide and dimethylformamide, alpha zein has a number average moleular weight of 21000-24000 daltons and shows no tendency to aggregate or dissociate. Beta zein exists in an aggregated state (dimer and higher forms) in dimethylformamide. Formamide dissociates the beta zein dimer into monomer units but aggregation to higher species occurs with increasing protein concentration.", "contents": "Molecular weight of an extremely hydrophobic protein, zein, in dimethylformamide and in formamide. Both alpha zein purified from a commericial preparation and beta zein prepared fresh from corn are soluble in the nonaqueous solvents formamide and dimethylformamide; in this regard zein resembles water soluble proteins such as insulin, ribonuclease, and lysozyme. On the basis of osmotic pressure measurements made in both formamide and dimethylformamide, alpha zein has a number average moleular weight of 21000-24000 daltons and shows no tendency to aggregate or dissociate. Beta zein exists in an aggregated state (dimer and higher forms) in dimethylformamide. Formamide dissociates the beta zein dimer into monomer units but aggregation to higher species occurs with increasing protein concentration."} {"id": "PMID:1260504", "title": "The metabolism of higher chlorinated benzene isomers.", "content": "The metabolism of the isomeric tri- and tetrachlorobenzene isomers, penta- and hexachlorobenzene was investigated in the rabbit. The major urinary metabolites of the isomeric tri- and tetrachlorobenzenes were identified as the corresponding tri- and tetrachlorophenols whose structures were confirmed by chromatographic analyses. The genesis of the formation of metabolites is discussed in terms of their possible arene oxide intermediates in which the NIH shift of a chlorine atom is observed in the oxidation of many of the isomers. Pentachlorobenzene is metabolized to give both pentachlorophenol and a dechlorination-hydroxylation product which was identified as 2,3,4,5-tetrachlorophenol. The hexachlorobenzene substrate did not give any phenolic metabolites.", "contents": "The metabolism of higher chlorinated benzene isomers. The metabolism of the isomeric tri- and tetrachlorobenzene isomers, penta- and hexachlorobenzene was investigated in the rabbit. The major urinary metabolites of the isomeric tri- and tetrachlorobenzenes were identified as the corresponding tri- and tetrachlorophenols whose structures were confirmed by chromatographic analyses. The genesis of the formation of metabolites is discussed in terms of their possible arene oxide intermediates in which the NIH shift of a chlorine atom is observed in the oxidation of many of the isomers. Pentachlorobenzene is metabolized to give both pentachlorophenol and a dechlorination-hydroxylation product which was identified as 2,3,4,5-tetrachlorophenol. The hexachlorobenzene substrate did not give any phenolic metabolites."} {"id": "PMID:1260505", "title": "The mechanism of the degradation of DNA by streptonigrin.", "content": "The production of single strand cleavage in covalently-closed circular-DNA by the antitumour agent streptonigrin (reduced in situ by NADH) is demonstrated using the ethidium bromide fluorescence assay described previously. The degradation dependent on oxygen is completely inhibited by superoxide dismutase (EC 1.15.1.1) suggesting the intermediacy of the superoxide radical anion in the degradation. However similar complete inhibition of DNA strand breakage by catalase (EC 1.11.1.6) indicates that the hydroxyl radical (formed by interaction of superoxide with hydrogen peroxide) is the primary reactive species. Cupric ion stimulates the cleavage reaction and cobaltous ion has no effect in keeping with model studies using quinolinequinones.", "contents": "The mechanism of the degradation of DNA by streptonigrin. The production of single strand cleavage in covalently-closed circular-DNA by the antitumour agent streptonigrin (reduced in situ by NADH) is demonstrated using the ethidium bromide fluorescence assay described previously. The degradation dependent on oxygen is completely inhibited by superoxide dismutase (EC 1.15.1.1) suggesting the intermediacy of the superoxide radical anion in the degradation. However similar complete inhibition of DNA strand breakage by catalase (EC 1.11.1.6) indicates that the hydroxyl radical (formed by interaction of superoxide with hydrogen peroxide) is the primary reactive species. Cupric ion stimulates the cleavage reaction and cobaltous ion has no effect in keeping with model studies using quinolinequinones."} {"id": "PMID:1260506", "title": "The influence of hydrocortisone on the synthesis and turnover of microvillous membrane glycoproteins in suckling rat intestine.", "content": "Synthesis and degradation of intestinal mucosal and microvillous membrane glycoproteins were studied in control suckling rats, and suckling rats given cortisol acetate by intraperitoneal injection for 3 days. Cortisol acetate had no effect on total uptake of radioactive glucosamine by the protein free compartment of rat intestine. Early incorporation of [1(-14)C]glucosamine by intestinal glycoproteins was enhanced by cortisol, but stimulation was the same in membrane and homogenate fractions. Polyacrylamide gel electrophoresis of membrane proteins solubilized with 2% sodium dodecyl sulphate demonstrated a cortisol dependent change, characterized by loss of faster travelling glycoproteins, and a corresponding shift in maximum labelling at 3 h from these glycoproteins to more slowly migrating glycoproteins. Degradation was studied qualitatively with a double isotope technique. Glycoprotein degradative rates appeared to be stimulated by cortisol, but similarly in membrane and total homogenate fractions. On polyacrylamide gels, the areas occupied by glycoproteins with the highest apparent degradative rates, corresponded closely with the areas of most active labelling at 3 h. The rate of degradation in the most actively labelled zone appeared to be higher after cortisol than in the controls. The results indicate that cortisol does not alter membrane composition by inhibiting degradation of selected glycoproteins, and are consistent with a model in which cortisol stimulates the synthesis of specific membrane glycoproteins in suckling rats, while inhibiting synthesis of other glycoproteins.", "contents": "The influence of hydrocortisone on the synthesis and turnover of microvillous membrane glycoproteins in suckling rat intestine. Synthesis and degradation of intestinal mucosal and microvillous membrane glycoproteins were studied in control suckling rats, and suckling rats given cortisol acetate by intraperitoneal injection for 3 days. Cortisol acetate had no effect on total uptake of radioactive glucosamine by the protein free compartment of rat intestine. Early incorporation of [1(-14)C]glucosamine by intestinal glycoproteins was enhanced by cortisol, but stimulation was the same in membrane and homogenate fractions. Polyacrylamide gel electrophoresis of membrane proteins solubilized with 2% sodium dodecyl sulphate demonstrated a cortisol dependent change, characterized by loss of faster travelling glycoproteins, and a corresponding shift in maximum labelling at 3 h from these glycoproteins to more slowly migrating glycoproteins. Degradation was studied qualitatively with a double isotope technique. Glycoprotein degradative rates appeared to be stimulated by cortisol, but similarly in membrane and total homogenate fractions. On polyacrylamide gels, the areas occupied by glycoproteins with the highest apparent degradative rates, corresponded closely with the areas of most active labelling at 3 h. The rate of degradation in the most actively labelled zone appeared to be higher after cortisol than in the controls. The results indicate that cortisol does not alter membrane composition by inhibiting degradation of selected glycoproteins, and are consistent with a model in which cortisol stimulates the synthesis of specific membrane glycoproteins in suckling rats, while inhibiting synthesis of other glycoproteins."} {"id": "PMID:1260507", "title": "Localization of oxalacetate keto-enol-tautomerase.", "content": "The intracellular location of oxalacetate keto-enol-tautomerase (oxaloacetate keto-enolisomerase) (EC 5.3.2.2) has been determined in two types of animal cells, rat liver and pig kidney. Two fractionation procedures were adopted and modified to suit each type of tissue. One fractionation procedure gave the soluble phase, microsomal and mitochondrial fractions, while the other isolated the nuclear fraction. The tautomerase is distributed among the soluble phase, microsomes and mitochondria in both tissues. Fractionation efficiency was checked by determining percentage recoveries of enzymic activity and total protein after each step, by microscopy studies and by determining the distribution of several marker enzymes.", "contents": "Localization of oxalacetate keto-enol-tautomerase. The intracellular location of oxalacetate keto-enol-tautomerase (oxaloacetate keto-enolisomerase) (EC 5.3.2.2) has been determined in two types of animal cells, rat liver and pig kidney. Two fractionation procedures were adopted and modified to suit each type of tissue. One fractionation procedure gave the soluble phase, microsomal and mitochondrial fractions, while the other isolated the nuclear fraction. The tautomerase is distributed among the soluble phase, microsomes and mitochondria in both tissues. Fractionation efficiency was checked by determining percentage recoveries of enzymic activity and total protein after each step, by microscopy studies and by determining the distribution of several marker enzymes."} {"id": "PMID:1260508", "title": "Wheat embryo ribonucleates. VI. Comparison of the 3'-hydroxyl termini in 'rapidly labelled' RNA from metabolizing wheat embryos with the corresponding termini in ribosomal RNA from differentiating embryos of wheat, barley, corn and pea.", "content": "The NaCl-insoluble (2.5 M, 0 degrees C) fraction of wheat embryo RNA (iRNA) can be labelled when wheat embryos are subjected to either short-term (0.5 h) or long-term (24 h) imbibition in a medium that contains tritium-labelled adenosine, guanosine, cytidine and uridine. Electrophoretic analyses reveal that, after short-term labelling, there is a broadly heterodisperse distribution of radioactivity in 'rapidly labelled' i[3H]RNA, but after long-term labelling, there is an essentially trimodal distribution of radioactivity in i[3H]RNA. End-group analyses reveal that, after short-term labelling, adenosine is the principal 3'-hydroxyl terminus in all centrifugal subfractions of 'rapidly labelled' i[3H]RNA, whereas cytidine (in 5.8S rRNA), guanosine (in 18S rRNA) and uridine (in 26S rRNA) are the principal 3'-hydroxyl termini in centrifugal subfractions of wheat embryo i[3H]RNA. Guanosine is also the principal 3'-hydroxyl terminus in the 18S rRNA of differentiating embryos excized from both monocotyledonous (wheat, barley, corn) and dicotyledonous (pea) seedlings. The implications that the end-group measurements may have for current views about the possible biochemical involvements of 3'-hydroxyl terminal sequences in both mRNA and 18SrRNA are subjects of discussion. Incidental to the principal investigation, an existing technique for analyzing the RNA contents of cellular materials has been appropriately modified to circumvent interference from uv-absorbing pigments, which, when present, prevent application of the method to plant materials.", "contents": "Wheat embryo ribonucleates. VI. Comparison of the 3'-hydroxyl termini in 'rapidly labelled' RNA from metabolizing wheat embryos with the corresponding termini in ribosomal RNA from differentiating embryos of wheat, barley, corn and pea. The NaCl-insoluble (2.5 M, 0 degrees C) fraction of wheat embryo RNA (iRNA) can be labelled when wheat embryos are subjected to either short-term (0.5 h) or long-term (24 h) imbibition in a medium that contains tritium-labelled adenosine, guanosine, cytidine and uridine. Electrophoretic analyses reveal that, after short-term labelling, there is a broadly heterodisperse distribution of radioactivity in 'rapidly labelled' i[3H]RNA, but after long-term labelling, there is an essentially trimodal distribution of radioactivity in i[3H]RNA. End-group analyses reveal that, after short-term labelling, adenosine is the principal 3'-hydroxyl terminus in all centrifugal subfractions of 'rapidly labelled' i[3H]RNA, whereas cytidine (in 5.8S rRNA), guanosine (in 18S rRNA) and uridine (in 26S rRNA) are the principal 3'-hydroxyl termini in centrifugal subfractions of wheat embryo i[3H]RNA. Guanosine is also the principal 3'-hydroxyl terminus in the 18S rRNA of differentiating embryos excized from both monocotyledonous (wheat, barley, corn) and dicotyledonous (pea) seedlings. The implications that the end-group measurements may have for current views about the possible biochemical involvements of 3'-hydroxyl terminal sequences in both mRNA and 18SrRNA are subjects of discussion. Incidental to the principal investigation, an existing technique for analyzing the RNA contents of cellular materials has been appropriately modified to circumvent interference from uv-absorbing pigments, which, when present, prevent application of the method to plant materials."} {"id": "PMID:1260509", "title": "Effects of diet on catabolism and excretion of (26-14C)cholesterol in rats.", "content": "The catabolism and excretion of [26-14C]cholesterol was studied in rats on semisynthetic and commercial diets low in fat or containing 15% butter or corn oil. Rats on the low fat commercial diet oxidized the labeled cholesterol to 14CO2 at more than twice the rate of those on the semisynthetic diet. Fecal excretion of labeled lipid was also somewhat higher with the commercial diet. The added fats had little effect on rate of oxidation of cholesterol but dietary corn oil stimulated fecal excretion of labeled lipid. The rate of loss of labeled cholesterol through oxidation and excretion showed a positive correlation with cholesterol biosynthesis, as measured previously by acetate incorporation into cholesterol in rats on the same kinds of diet. A simple method for efficient trapping and counting of 14CO2 was developed, which facilitated measurement of low levels of 14CO2 in expired air. Estimation of bile acid production from the rate of oxidation of [26-14C]cholesterol to expired 14CO2 and the specific activity of plasma cholesterol gave somewhat higher values than those obtained by other methods. Possible reasons for this difference are discussed.", "contents": "Effects of diet on catabolism and excretion of (26-14C)cholesterol in rats. The catabolism and excretion of [26-14C]cholesterol was studied in rats on semisynthetic and commercial diets low in fat or containing 15% butter or corn oil. Rats on the low fat commercial diet oxidized the labeled cholesterol to 14CO2 at more than twice the rate of those on the semisynthetic diet. Fecal excretion of labeled lipid was also somewhat higher with the commercial diet. The added fats had little effect on rate of oxidation of cholesterol but dietary corn oil stimulated fecal excretion of labeled lipid. The rate of loss of labeled cholesterol through oxidation and excretion showed a positive correlation with cholesterol biosynthesis, as measured previously by acetate incorporation into cholesterol in rats on the same kinds of diet. A simple method for efficient trapping and counting of 14CO2 was developed, which facilitated measurement of low levels of 14CO2 in expired air. Estimation of bile acid production from the rate of oxidation of [26-14C]cholesterol to expired 14CO2 and the specific activity of plasma cholesterol gave somewhat higher values than those obtained by other methods. Possible reasons for this difference are discussed."} {"id": "PMID:1260510", "title": "Persistent effects of ouabain treatment on human lymphocytes: synthesis of DNA, RNA and protein in stimulated and unstimulated cells.", "content": "Pretreatment of human lymphocytes for 2 days in 2 X 10(-6)M ouabain caused irreversible loss of their subsequent capacity to stimulate in the mixed lymphocyte reaction (MLR). Pretreatment for the same period with 10(-7)M ouabain resulted in an enhanced incorporation of thymidine into DNA of the responding cells in the MLR; this effect was also on the stimulating cells, as previously reported by Christen et al. (Cell, Immunol. 19, 137-142 (1975)). Pretreatment of stimulating lymphocytes with 10(-7)M ouabain caused a persistent but reversible inhibition of the synthesis of RNA and protein in the MLR; peak incorporation of labelled uridine or alanine reached the same level as that of the control cultures, but 24 h later. Exactly the same persistent but reversible inhibition was found in the case of DNA syntheis of cells pretreated with 10(-7)M ouabain and then stimulated by antigens (streptolysin-O and varidase) or by mitogens (phytohemagglutinin and concanavalin A); the same level of incorporation of labelled thymidine occurred but 24-48 h later than in the case of the controls. Pretreatment with the cardiotonic steroid under these conditions also resulted in a pronounced inhibition of the basal, unstimulated levels of RNA and protein synthesis in the case of both control lymphocytes and those which had been treated with mitomycin C. The effects of ouabain pretreatment on basal RNA and protein synthesis were identical for both 2 X 10(-6)M and for 10(-7)M; the effect of pretreatment of stimulating cells with these two concentrations was completely opposite: irreversible inhibition of the proliferative response of allogeneic responding cells at the former concentration and delayed activation at the latter.", "contents": "Persistent effects of ouabain treatment on human lymphocytes: synthesis of DNA, RNA and protein in stimulated and unstimulated cells. Pretreatment of human lymphocytes for 2 days in 2 X 10(-6)M ouabain caused irreversible loss of their subsequent capacity to stimulate in the mixed lymphocyte reaction (MLR). Pretreatment for the same period with 10(-7)M ouabain resulted in an enhanced incorporation of thymidine into DNA of the responding cells in the MLR; this effect was also on the stimulating cells, as previously reported by Christen et al. (Cell, Immunol. 19, 137-142 (1975)). Pretreatment of stimulating lymphocytes with 10(-7)M ouabain caused a persistent but reversible inhibition of the synthesis of RNA and protein in the MLR; peak incorporation of labelled uridine or alanine reached the same level as that of the control cultures, but 24 h later. Exactly the same persistent but reversible inhibition was found in the case of DNA syntheis of cells pretreated with 10(-7)M ouabain and then stimulated by antigens (streptolysin-O and varidase) or by mitogens (phytohemagglutinin and concanavalin A); the same level of incorporation of labelled thymidine occurred but 24-48 h later than in the case of the controls. Pretreatment with the cardiotonic steroid under these conditions also resulted in a pronounced inhibition of the basal, unstimulated levels of RNA and protein synthesis in the case of both control lymphocytes and those which had been treated with mitomycin C. The effects of ouabain pretreatment on basal RNA and protein synthesis were identical for both 2 X 10(-6)M and for 10(-7)M; the effect of pretreatment of stimulating cells with these two concentrations was completely opposite: irreversible inhibition of the proliferative response of allogeneic responding cells at the former concentration and delayed activation at the latter."} {"id": "PMID:1260511", "title": "The development of dermal lesions and alopecia in male rats fed rapeseed oil.", "content": "For 8 weeks 10 male weanling Sprague-Dawley rats were fed a semisynthetic diet containing by weight either 20% corn oil or rapeseed oils containing different amounts of erucic acid (Brassica napus var. Zephyr, 0.6%; B. napus var. Oro, 1.8%; B. campestris var. Span, 4.8%; or B. campestris var. Echo and Arlo, i.e., regular rapeseed oil, 23.6%). At 4-5 weeks after the experiment began, rats receiving the diets containing rapeseed oil showed evidence of alopecia and developed scaly, hemorrhagic, and necrotic tails, as well as scaliness of the feet, similar to the lesions described in essential fatty acid (EFA) deficiency. This condition became most severe between 5 and 8 weeks and had disappeared by 14 weeks. Fatty acid analysis of the diets and tissues of the animals did not reveal any evidence of EFA deficiency. It is suggested that these symptoms observed might be related to a possible inhibition of prostaglandin biosynthesis in rats fed rapeseed oils.", "contents": "The development of dermal lesions and alopecia in male rats fed rapeseed oil. For 8 weeks 10 male weanling Sprague-Dawley rats were fed a semisynthetic diet containing by weight either 20% corn oil or rapeseed oils containing different amounts of erucic acid (Brassica napus var. Zephyr, 0.6%; B. napus var. Oro, 1.8%; B. campestris var. Span, 4.8%; or B. campestris var. Echo and Arlo, i.e., regular rapeseed oil, 23.6%). At 4-5 weeks after the experiment began, rats receiving the diets containing rapeseed oil showed evidence of alopecia and developed scaly, hemorrhagic, and necrotic tails, as well as scaliness of the feet, similar to the lesions described in essential fatty acid (EFA) deficiency. This condition became most severe between 5 and 8 weeks and had disappeared by 14 weeks. Fatty acid analysis of the diets and tissues of the animals did not reveal any evidence of EFA deficiency. It is suggested that these symptoms observed might be related to a possible inhibition of prostaglandin biosynthesis in rats fed rapeseed oils."} {"id": "PMID:1260512", "title": "Storage and release of labelled acetylcholine in the myenteric plexus of the guinea-pig ileum.", "content": "Guinea-pig ileum myenteric plexus-longitudinal muscle preparation was superfused with [3H]choline for 15 min either without being stimulated or during field stimulation at 0.1 or 16 Hz; the preparation was then either removed immediately or after 75- or 135-min superfusion with hemicholinium-3 (HC-3) and the total acetylcholine (ACh) and [3H]ACh contents were determined. For measuring the release of [3H]ACh the preparation was stimulated for 60 min the second time at 0.1 or 16 HZ in the presence of hemicholinium. Exposure to [3H]choline without stimulation resulted in the formation of [3H]ACh stores which were maintained in the first 75 min but decreased therafter. Labelling during stimulation at 16 Hz produced the largest and best maintained [3H]ACh content. Following labelling during 0.1-Hz stimulation, more label could be released than following labelling in the absence of stimulation. Labelling during 16-Hz stimulation did not increase any further in fool of [3H]ACh accessible to release by 0.1-Hz stimulation, but caused a 2.5 times increase in the pool from which Hz stimulation released [3H]ACh. These results suggest that two populations of cholinergic neurons exist in the myenteric plexus, one activated only by high frequency stimulation, the other by both high and low frequency stimulation.", "contents": "Storage and release of labelled acetylcholine in the myenteric plexus of the guinea-pig ileum. Guinea-pig ileum myenteric plexus-longitudinal muscle preparation was superfused with [3H]choline for 15 min either without being stimulated or during field stimulation at 0.1 or 16 Hz; the preparation was then either removed immediately or after 75- or 135-min superfusion with hemicholinium-3 (HC-3) and the total acetylcholine (ACh) and [3H]ACh contents were determined. For measuring the release of [3H]ACh the preparation was stimulated for 60 min the second time at 0.1 or 16 HZ in the presence of hemicholinium. Exposure to [3H]choline without stimulation resulted in the formation of [3H]ACh stores which were maintained in the first 75 min but decreased therafter. Labelling during stimulation at 16 Hz produced the largest and best maintained [3H]ACh content. Following labelling during 0.1-Hz stimulation, more label could be released than following labelling in the absence of stimulation. Labelling during 16-Hz stimulation did not increase any further in fool of [3H]ACh accessible to release by 0.1-Hz stimulation, but caused a 2.5 times increase in the pool from which Hz stimulation released [3H]ACh. These results suggest that two populations of cholinergic neurons exist in the myenteric plexus, one activated only by high frequency stimulation, the other by both high and low frequency stimulation."} {"id": "PMID:1260513", "title": "Asialoglycoprotein clearance in the chicken: evidence for the lack of a hepatic asialoglycoprotein receptor.", "content": "The behaviour of desialylated human and chicken acid alpha1-glycoproteins is reported in chickens. Although desialylation resulted in accelerated disappearance rates from the plasma of both proteins, nevertheless the asialoproteins were eliminated much more slowly than expected on the basis of earlier observations in mammals. Analysis of tissue radioactivities, including kidney, liver, lung and spleen, failed to demonstrate any accumulation of the labeled asialoproteins in the liver, which is contrary to the situation in mammals. The main pathway for the elimination of desialylated human acid alpha1-glycoprotein in the chicken is via the kidney (tubular catabolism and/or urinary excretion). The clearance of desialylated chicken acid alpha1-glycoprotein is more complex as it involves the kidney as well as the reticuloendothelial system. These findings indicate that, unlike mammals, chickens do not possess a hepatic plasma membrane receptor for asialoglycoproteins. This raises the possibility that the presence or absence of this specific receptor may constitute a fundamental biological difference between mammals and birds.", "contents": "Asialoglycoprotein clearance in the chicken: evidence for the lack of a hepatic asialoglycoprotein receptor. The behaviour of desialylated human and chicken acid alpha1-glycoproteins is reported in chickens. Although desialylation resulted in accelerated disappearance rates from the plasma of both proteins, nevertheless the asialoproteins were eliminated much more slowly than expected on the basis of earlier observations in mammals. Analysis of tissue radioactivities, including kidney, liver, lung and spleen, failed to demonstrate any accumulation of the labeled asialoproteins in the liver, which is contrary to the situation in mammals. The main pathway for the elimination of desialylated human acid alpha1-glycoprotein in the chicken is via the kidney (tubular catabolism and/or urinary excretion). The clearance of desialylated chicken acid alpha1-glycoprotein is more complex as it involves the kidney as well as the reticuloendothelial system. These findings indicate that, unlike mammals, chickens do not possess a hepatic plasma membrane receptor for asialoglycoproteins. This raises the possibility that the presence or absence of this specific receptor may constitute a fundamental biological difference between mammals and birds."} {"id": "PMID:1260514", "title": "Effects of a series of alcohols on the binding of a fluorescent dye to erythrocyte membranes.", "content": "1. The effects of a series of aliphatic alcohols (methanol to octanol) on membrane proteins of erythrocytes were studied by monitoring the flueorescence of a dye (1-anilino-8-naphthalenesulfonic acid (ANS)) that adsorbs to erythrocyte ghost membranes. Low concentrations of all the alcohols reduced the ANS fluorescence of the membrane-ANS suspensions; lent to those which protect against hypotonic hemolysis on intact erythrocytes; higher concentrations markedly increased the fluorescence. Ethanol and methanol decreased ANS fluorescence at all concentrations. 2. Lytic concentrations of saponin did not increase ANS fluorescence and did not modify the membrane action of the alcohols. 3. None of these effects were observed in liposomes prepared from lipid extracts of the erythrocyte membrane. 4. Since the apparent dissociation constant for the ANS-membrane interaction was unchanged in the presence of the alcohols, it was assumed that the fluorescence changes anesthetic concentration of the alcohols alter the conformation of membrane proteins, as indicated by the decreased number of ANS binding sites.", "contents": "Effects of a series of alcohols on the binding of a fluorescent dye to erythrocyte membranes. 1. The effects of a series of aliphatic alcohols (methanol to octanol) on membrane proteins of erythrocytes were studied by monitoring the flueorescence of a dye (1-anilino-8-naphthalenesulfonic acid (ANS)) that adsorbs to erythrocyte ghost membranes. Low concentrations of all the alcohols reduced the ANS fluorescence of the membrane-ANS suspensions; lent to those which protect against hypotonic hemolysis on intact erythrocytes; higher concentrations markedly increased the fluorescence. Ethanol and methanol decreased ANS fluorescence at all concentrations. 2. Lytic concentrations of saponin did not increase ANS fluorescence and did not modify the membrane action of the alcohols. 3. None of these effects were observed in liposomes prepared from lipid extracts of the erythrocyte membrane. 4. Since the apparent dissociation constant for the ANS-membrane interaction was unchanged in the presence of the alcohols, it was assumed that the fluorescence changes anesthetic concentration of the alcohols alter the conformation of membrane proteins, as indicated by the decreased number of ANS binding sites."} {"id": "PMID:1260515", "title": "Propranolol antagonism to the effect of furosemide on the compostion of endolymph in guinea pigs.", "content": "Furosemide, administered intravenously (50 mg/kg) to guinea pigs, caused an increase in the sodium concentration and a decrease in the potassium concentration of endolymph, and a fall in the endolymphatic potential. The furosemide-induced electrolyte changes were prevented by pretreatment of five guinea pigs with propranolol given intravenously (2 mg/kg). The fall in the endolymphatic potential was not prevented by propranolol. Local administration of furosemide to the perilymphatic or endolymphatic space caused a fall in the endolymphatic potential, but had no effect upon the concentrations os sodium and potassium of endolymph. These studies provide additional information suggesting the mutual independence of the endolymphatic potential and sodium and potassium concentration gradients.", "contents": "Propranolol antagonism to the effect of furosemide on the compostion of endolymph in guinea pigs. Furosemide, administered intravenously (50 mg/kg) to guinea pigs, caused an increase in the sodium concentration and a decrease in the potassium concentration of endolymph, and a fall in the endolymphatic potential. The furosemide-induced electrolyte changes were prevented by pretreatment of five guinea pigs with propranolol given intravenously (2 mg/kg). The fall in the endolymphatic potential was not prevented by propranolol. Local administration of furosemide to the perilymphatic or endolymphatic space caused a fall in the endolymphatic potential, but had no effect upon the concentrations os sodium and potassium of endolymph. These studies provide additional information suggesting the mutual independence of the endolymphatic potential and sodium and potassium concentration gradients."} {"id": "PMID:1260516", "title": "Effects on tissue and electrolytes of a mineralocorticoid blocker during DOCA-induced potassium depletion.", "content": "Chronic experiments were carried out on three groups of rats to evaluate tissue and electrolyte effects of a mineralocorticoid blocker canrenoate potassium (SC-14266) during DOCA-induced hypokalemic metabolic alkalosis. Group I animals received DOCA alone, group II received DOCA plus canrenoate, while group III received canrenoate alone. The daily dose ratio (per kilogram of body weight) was 180 mg canrenoate-0.45 mg DOCA. All animals ate a synthetic diet and drank 0.15 N NaHCO3. Group II animals demonstrated a lesser degree of metabolic alkalosis and a higher muscle potassium content when compared with group I rats. The most conspicuous histological abnormality was myocardial necrosis, the degree and extent of which was impressively reduced by the blocking agent.", "contents": "Effects on tissue and electrolytes of a mineralocorticoid blocker during DOCA-induced potassium depletion. Chronic experiments were carried out on three groups of rats to evaluate tissue and electrolyte effects of a mineralocorticoid blocker canrenoate potassium (SC-14266) during DOCA-induced hypokalemic metabolic alkalosis. Group I animals received DOCA alone, group II received DOCA plus canrenoate, while group III received canrenoate alone. The daily dose ratio (per kilogram of body weight) was 180 mg canrenoate-0.45 mg DOCA. All animals ate a synthetic diet and drank 0.15 N NaHCO3. Group II animals demonstrated a lesser degree of metabolic alkalosis and a higher muscle potassium content when compared with group I rats. The most conspicuous histological abnormality was myocardial necrosis, the degree and extent of which was impressively reduced by the blocking agent."} {"id": "PMID:1260517", "title": "Descending influences of periaqueductal gray matter and somatosensory cerebral cortex on neurones in trigeminal brain stem nuclei.", "content": "Single relay (to thalamus) and nonrelay neurones that responded to innocuous and/or noxious oral-facial stimuli were located in trigeminal brain stem nuclei oralis and caudalis. The responses of the cells and the digastric muscle to these stimuli were tested with conditioning stimulation of the periaqueductal gray matter (PGM) and somatosensory cerebral cortex in cats. A greater suppression of nociceptive responses with PGM stimulation was noted, and this effect may contribute to the profound analgesic action that has been reported to occur with PGM stimulation.", "contents": "Descending influences of periaqueductal gray matter and somatosensory cerebral cortex on neurones in trigeminal brain stem nuclei. Single relay (to thalamus) and nonrelay neurones that responded to innocuous and/or noxious oral-facial stimuli were located in trigeminal brain stem nuclei oralis and caudalis. The responses of the cells and the digastric muscle to these stimuli were tested with conditioning stimulation of the periaqueductal gray matter (PGM) and somatosensory cerebral cortex in cats. A greater suppression of nociceptive responses with PGM stimulation was noted, and this effect may contribute to the profound analgesic action that has been reported to occur with PGM stimulation."} {"id": "PMID:1260518", "title": "The interaction of glutamic and aspartic acids with excitatory amino acid receptors in the mammalian central nervous system.", "content": "Firing rates of single thalamic neurones of the cat and the rat have been measured as functions of the currents used to apply glutamic and aspartic acids electrophoretically. Hill plots of the data suggest that three amino acid molecules are probably required to activate an excitatory receptor.", "contents": "The interaction of glutamic and aspartic acids with excitatory amino acid receptors in the mammalian central nervous system. Firing rates of single thalamic neurones of the cat and the rat have been measured as functions of the currents used to apply glutamic and aspartic acids electrophoretically. Hill plots of the data suggest that three amino acid molecules are probably required to activate an excitatory receptor."} {"id": "PMID:1260519", "title": "Intracellular Mg2+ increases neuronal excitability.", "content": "Injection of Mg2+ into spinal motoneurons of cats leads to a depolarization, associated with a fall in membrane conductance, diminution in post-spike hyperpolarization, and increased excitability. This action has an apparent reversal level substantially more negative than the resting potential, and can be ascribed to a fall in K+ membrane conductance. Since these effects are opposite to those produced by intracellular Ca2+, it is suggested that Mg2+ probably competes with Ca2+ at the Ca2+-activated K+ ionophoreal free ionophores. Neuronal excitability can be regulated by the ratio of internal free Ca2+/Mg2+.", "contents": "Intracellular Mg2+ increases neuronal excitability. Injection of Mg2+ into spinal motoneurons of cats leads to a depolarization, associated with a fall in membrane conductance, diminution in post-spike hyperpolarization, and increased excitability. This action has an apparent reversal level substantially more negative than the resting potential, and can be ascribed to a fall in K+ membrane conductance. Since these effects are opposite to those produced by intracellular Ca2+, it is suggested that Mg2+ probably competes with Ca2+ at the Ca2+-activated K+ ionophoreal free ionophores. Neuronal excitability can be regulated by the ratio of internal free Ca2+/Mg2+."} {"id": "PMID:1260520", "title": "DNA relatedness among species of Enterobacter and Serratia.", "content": "Species of Enterobacter and Serratia were examined for deoxyribonucleic acid relatedness to Klebsielleae, to atypical erwiniae, and to other members of Enterobacteriaceae. Deoxyribonucleic acid hybridization and then hydroxyapatite chromatography was the technique used to assess relatedness. Strains of Enterobacter cloacae formed two separate hybridization groups that correlate with the presence or absence of yellow pigment. Pigmented E. cloacae were 75-100% related, but they were only 40-50% related to unpigmented strains. Conversely, unpigmented strains were 70% or more related but were only 40-50% related to the pigmented strains. Both pigmented and unpigmented E. cloacae were 40-45% related to Enterobacter aerogenes and klebsiellae, and 20-30% related to Serratia species and Enterobacter hafniae. Atypical erwiniae were highly related to E. cloacae. Serratia marcescens strains formed one closely related group. Serratia liquefaciens strains formed a single, more disperse, relatedness group, as did isolates of Serratia rubidaea. These species were related throughout a substantial portion of their genomes. A group of lysine-positive \"Citrobacter-like\" strains were 40-50% related to Serratia species. Only four E. hafniae strains were tested. Two of these were highly related, while the other two were only 50% related to the reference strain. Enterobacter hafniae was only 15-20% related to other Enterobacteriaceae.", "contents": "DNA relatedness among species of Enterobacter and Serratia. Species of Enterobacter and Serratia were examined for deoxyribonucleic acid relatedness to Klebsielleae, to atypical erwiniae, and to other members of Enterobacteriaceae. Deoxyribonucleic acid hybridization and then hydroxyapatite chromatography was the technique used to assess relatedness. Strains of Enterobacter cloacae formed two separate hybridization groups that correlate with the presence or absence of yellow pigment. Pigmented E. cloacae were 75-100% related, but they were only 40-50% related to unpigmented strains. Conversely, unpigmented strains were 70% or more related but were only 40-50% related to the pigmented strains. Both pigmented and unpigmented E. cloacae were 40-45% related to Enterobacter aerogenes and klebsiellae, and 20-30% related to Serratia species and Enterobacter hafniae. Atypical erwiniae were highly related to E. cloacae. Serratia marcescens strains formed one closely related group. Serratia liquefaciens strains formed a single, more disperse, relatedness group, as did isolates of Serratia rubidaea. These species were related throughout a substantial portion of their genomes. A group of lysine-positive \"Citrobacter-like\" strains were 40-50% related to Serratia species. Only four E. hafniae strains were tested. Two of these were highly related, while the other two were only 50% related to the reference strain. Enterobacter hafniae was only 15-20% related to other Enterobacteriaceae."} {"id": "PMID:1260521", "title": "Morphological, physiological, and biochemical characteristics of some violet-pigmented bacteria isolated from seawater.", "content": "Sixteen violet-pigmented heterotrophic bacilli were isolated from Mediterranean coastal waters. Morphological and physiological studies showed that they have a number of characteristics specific to the genus Chromobacterium. However, the absence of catalase, the presence of oxidase, and, more especially, the low percentage of bases guanine and cytosine in their DNA exclude them from the genus. The specificity of some characters assigned to Chromobacterium can thus be discussed. Several features allow us to consider such bacteria as being related to the genus Alteromonas; their consistency within the 16 strains investigated leads us to consider them as a single species, for which the specific name Alteromonas luteo-violaceus (sp. nov.) is proposed.", "contents": "Morphological, physiological, and biochemical characteristics of some violet-pigmented bacteria isolated from seawater. Sixteen violet-pigmented heterotrophic bacilli were isolated from Mediterranean coastal waters. Morphological and physiological studies showed that they have a number of characteristics specific to the genus Chromobacterium. However, the absence of catalase, the presence of oxidase, and, more especially, the low percentage of bases guanine and cytosine in their DNA exclude them from the genus. The specificity of some characters assigned to Chromobacterium can thus be discussed. Several features allow us to consider such bacteria as being related to the genus Alteromonas; their consistency within the 16 strains investigated leads us to consider them as a single species, for which the specific name Alteromonas luteo-violaceus (sp. nov.) is proposed."} {"id": "PMID:1260522", "title": "Glycerol metabolism in Rhizobium.", "content": "Four strains of Rhizobium japonicum and one strain of R. trifolii were grown on glycerol and found to contain a soluble ATP-glycerol kinase and a particulate glycerolphosphate dehydrogenase. Both enzymes are induced by glycerol. The presence of NAD+-or NADP+-glycerol dehydrogenase was not detected in any of the strains. No significant differences were found in the glycerol metabolic pathway between fast-and slow-growing rhizobia.", "contents": "Glycerol metabolism in Rhizobium. Four strains of Rhizobium japonicum and one strain of R. trifolii were grown on glycerol and found to contain a soluble ATP-glycerol kinase and a particulate glycerolphosphate dehydrogenase. Both enzymes are induced by glycerol. The presence of NAD+-or NADP+-glycerol dehydrogenase was not detected in any of the strains. No significant differences were found in the glycerol metabolic pathway between fast-and slow-growing rhizobia."} {"id": "PMID:1260523", "title": "Temporal origin of viral phospholipids of the enveloped bacteriophage phi 6.", "content": "The enveloped bacteriophage phi 6 contains a higher relative level of the negatively charged phospholipid phosphatidylglycerol than is found in the membranes of the host bacterium. During infection of Pseudomonas phaseolicola with phi 6, the level of phosphatidylglycerol synthesis increases significantly. The lipid used to form the viral envelope consists almost entirely of cellular phospholipids synthesized before infection and phosphatidylglycerol synthesized after infection. Based on these and previously published results, a speculative model for this viral envelope formation process is presented.", "contents": "Temporal origin of viral phospholipids of the enveloped bacteriophage phi 6. The enveloped bacteriophage phi 6 contains a higher relative level of the negatively charged phospholipid phosphatidylglycerol than is found in the membranes of the host bacterium. During infection of Pseudomonas phaseolicola with phi 6, the level of phosphatidylglycerol synthesis increases significantly. The lipid used to form the viral envelope consists almost entirely of cellular phospholipids synthesized before infection and phosphatidylglycerol synthesized after infection. Based on these and previously published results, a speculative model for this viral envelope formation process is presented."} {"id": "PMID:1260524", "title": "The nuclear DNA-dependent ribonucleic acid polymerases of the dermatophytic fungus Microsporum gypseum.", "content": "The DNA-dependent RNA polymerases of the dermatophytic fungus Microsporum gypseum were partially characterized. Nuclear extracts prepared from vegetative mycelia were fractionated by DEAE-Sephadex chromatography into three enzyme species which resembled in most of their characteristics those of other eukaryotic organisms.", "contents": "The nuclear DNA-dependent ribonucleic acid polymerases of the dermatophytic fungus Microsporum gypseum. The DNA-dependent RNA polymerases of the dermatophytic fungus Microsporum gypseum were partially characterized. Nuclear extracts prepared from vegetative mycelia were fractionated by DEAE-Sephadex chromatography into three enzyme species which resembled in most of their characteristics those of other eukaryotic organisms."} {"id": "PMID:1260525", "title": "Enterotoxin B formation by fermentation mutants of Staphylococcus aureus.", "content": "An appreciable fraction of carbohydrate-negative (car) mutants of Staphylococcus aureus strains ATCC 14458, 778, and S-6 exhibit increased enterotoxin B (SEB) production. In addition, some lac and mtl mutants of these strains also display enhanced SEB formation. All such mutants appear to be point mutations. Mutagen-induced reversions of high SEB producing car, mtl, or lac mutants yield varying amounts of SEB and some clones seem to be restored to the characteristics of the parent type. A few sequentially isolated lac, mtl double mutants of strain 778 elaborate much more or much less SEB than either the lac or the mtl single mutants.", "contents": "Enterotoxin B formation by fermentation mutants of Staphylococcus aureus. An appreciable fraction of carbohydrate-negative (car) mutants of Staphylococcus aureus strains ATCC 14458, 778, and S-6 exhibit increased enterotoxin B (SEB) production. In addition, some lac and mtl mutants of these strains also display enhanced SEB formation. All such mutants appear to be point mutations. Mutagen-induced reversions of high SEB producing car, mtl, or lac mutants yield varying amounts of SEB and some clones seem to be restored to the characteristics of the parent type. A few sequentially isolated lac, mtl double mutants of strain 778 elaborate much more or much less SEB than either the lac or the mtl single mutants."} {"id": "PMID:1260526", "title": "Studies of the cellular and free lipopolysaccharides form Neisseria canis and N. subflava.", "content": "Cellular and free lipopolysaccharides (LPS) obtained from Neisseria canis and N. subflava were essentially identical. Both cellular and free lipopolysaccharides contained O-polysaccharides of the following composition: L-rhamnose (46 mol), D-glucose (16 mol), L-glycero-D-manno-heptose (2 mol), ethanolamine (2 mol), 3-deoxy-D-manno-octulosonic acid (1 mol), and phosphate (1.5 mol). The core oligosaccharide, which was common to the cellular and free LPS of both organisms, contained L-rhamnose (4 mol), D-glucose (2 mol), L-glycero-D-manno-heptose (2 mol), 3-deoxy-D-manno-octulosonic acid (1 mol), ethanolamine (2 mol), and phosphate (1.5 mol). Accumulated results on LPS composition and structure indicated that Neisseria perflava, N. subflava, and N. flava could not be combined into a single species. On the basis of its nutritional requirements and LPS structure, N. canis could be considered a strain of N. subflava.", "contents": "Studies of the cellular and free lipopolysaccharides form Neisseria canis and N. subflava. Cellular and free lipopolysaccharides (LPS) obtained from Neisseria canis and N. subflava were essentially identical. Both cellular and free lipopolysaccharides contained O-polysaccharides of the following composition: L-rhamnose (46 mol), D-glucose (16 mol), L-glycero-D-manno-heptose (2 mol), ethanolamine (2 mol), 3-deoxy-D-manno-octulosonic acid (1 mol), and phosphate (1.5 mol). The core oligosaccharide, which was common to the cellular and free LPS of both organisms, contained L-rhamnose (4 mol), D-glucose (2 mol), L-glycero-D-manno-heptose (2 mol), 3-deoxy-D-manno-octulosonic acid (1 mol), ethanolamine (2 mol), and phosphate (1.5 mol). Accumulated results on LPS composition and structure indicated that Neisseria perflava, N. subflava, and N. flava could not be combined into a single species. On the basis of its nutritional requirements and LPS structure, N. canis could be considered a strain of N. subflava."} {"id": "PMID:1260527", "title": "Morphology and host range of virulent phages of lotus rhizobia.", "content": "Nineteen virulent bacteriophages for fast- and slow-growing rhizobia were isolated. Most of the phage isolates were of two morphological types, and these showed specificity for either the fast- or the slow-growing rhizobia. The ecological distribution, morphology, and host range of the phages is presented. Classification of lotus rhizobia is discussed on the basis of phage typing.", "contents": "Morphology and host range of virulent phages of lotus rhizobia. Nineteen virulent bacteriophages for fast- and slow-growing rhizobia were isolated. Most of the phage isolates were of two morphological types, and these showed specificity for either the fast- or the slow-growing rhizobia. The ecological distribution, morphology, and host range of the phages is presented. Classification of lotus rhizobia is discussed on the basis of phage typing."} {"id": "PMID:1260528", "title": "The accumulation of succinate by the yeast Brettanomyces bruxellensis.", "content": "The metabolism of Brettanomyces bruxellensis was investigated to determine the metabolic block responsible for the accumulation of acetate seen in cultures of this yeast. In glucose-grown cultures the major non-volatile intracellular organic acide was succinic acid. These cultures also had low levels of succinic dehydrogenase (succinate dehydrogenase, EC 1.3.99.1) and did not produce CO2 from the carbons of ethanol. It was concluded that a block in the oxidation of ethanol occurred at the level of succinic dehydrogenase. If glucose-grown cultures were transferred to ethanol medium, the block in the metabolism of ethanol was partially overcome; the level of succinic dehydrogenase increased, the concentration of the intracellular succinate decreased, and CO2 could be produced from C-1 of ethanol.", "contents": "The accumulation of succinate by the yeast Brettanomyces bruxellensis. The metabolism of Brettanomyces bruxellensis was investigated to determine the metabolic block responsible for the accumulation of acetate seen in cultures of this yeast. In glucose-grown cultures the major non-volatile intracellular organic acide was succinic acid. These cultures also had low levels of succinic dehydrogenase (succinate dehydrogenase, EC 1.3.99.1) and did not produce CO2 from the carbons of ethanol. It was concluded that a block in the oxidation of ethanol occurred at the level of succinic dehydrogenase. If glucose-grown cultures were transferred to ethanol medium, the block in the metabolism of ethanol was partially overcome; the level of succinic dehydrogenase increased, the concentration of the intracellular succinate decreased, and CO2 could be produced from C-1 of ethanol."} {"id": "PMID:1260529", "title": "Microbial utilization of raw and hydrogenated shale oils.", "content": "The biodegradability of raw and hydrogenated shale oils prepared by a retort process were studied under psychrophilic and mesophilic conditions. Changes in bacterial numbers and the chemical composition of the oils were monitored using a plate count and chromatographic techniques respectively. Raw shale oil was found to be relatively resistant to microbial attack whereas hydrogenated shale oil was readily utilized for microbial growth. Populations enriched on raw shale oil had a reduced ability to use hydrogenated shale oil under similar conditions. Gram-negative rods predominated in all enrichment populations. It is recommended that to facilitate clean up of shale oil spills, raw shale oil be reduced at the extraction site before transport.", "contents": "Microbial utilization of raw and hydrogenated shale oils. The biodegradability of raw and hydrogenated shale oils prepared by a retort process were studied under psychrophilic and mesophilic conditions. Changes in bacterial numbers and the chemical composition of the oils were monitored using a plate count and chromatographic techniques respectively. Raw shale oil was found to be relatively resistant to microbial attack whereas hydrogenated shale oil was readily utilized for microbial growth. Populations enriched on raw shale oil had a reduced ability to use hydrogenated shale oil under similar conditions. Gram-negative rods predominated in all enrichment populations. It is recommended that to facilitate clean up of shale oil spills, raw shale oil be reduced at the extraction site before transport."} {"id": "PMID:1260530", "title": "Morphological modifications of cells of Clostridium pasteurianum caused by growth on sulfite.", "content": "The morphology of Clostridium pasteurianum cells grown on 10(-2) M SO32- showed significant alteration in cell shape and the absence of the electron translucent reserve polysaccharide (amylopectin) when compared to sulfate-grown cells. At the lower sulfite concentrations (10(-3) and 10(-4)M SO32-) the cells showed the cytoplasmic changes noted above but the cell shapes were not modified.", "contents": "Morphological modifications of cells of Clostridium pasteurianum caused by growth on sulfite. The morphology of Clostridium pasteurianum cells grown on 10(-2) M SO32- showed significant alteration in cell shape and the absence of the electron translucent reserve polysaccharide (amylopectin) when compared to sulfate-grown cells. At the lower sulfite concentrations (10(-3) and 10(-4)M SO32-) the cells showed the cytoplasmic changes noted above but the cell shapes were not modified."} {"id": "PMID:1260531", "title": "Degradation of homogentisate by strains of Bacillus and Moraxella.", "content": "The metabolic pathways whereby strains of Moraxella and Bacillus degrade homogentisate (2,5-dihydroxyphenylacetate) are delineated. The Moraxella (strain OA3) is shown to degrade homogentisate via the pathway previously described in liver: homogentisate is cleaved by a 1,2-dioxygenase (E.C 1.13.11.5) yielding maleylacetoacetate which is isomerized by a GSH-dependent isomerase to fumarylacetoacetate before hydrolysis to acetoacetate and fumarate. A strain of Bacillus (B11c) is shown to catabolize homogentisate via a previously undescribed version of the above sequence: homogentisate is cleaved by a 1,2-dioxygenase (E.C 1.13.11.5) yielding maleylacetoacetate which is hydrolyzed directly to acetoacetate and maleate.", "contents": "Degradation of homogentisate by strains of Bacillus and Moraxella. The metabolic pathways whereby strains of Moraxella and Bacillus degrade homogentisate (2,5-dihydroxyphenylacetate) are delineated. The Moraxella (strain OA3) is shown to degrade homogentisate via the pathway previously described in liver: homogentisate is cleaved by a 1,2-dioxygenase (E.C 1.13.11.5) yielding maleylacetoacetate which is isomerized by a GSH-dependent isomerase to fumarylacetoacetate before hydrolysis to acetoacetate and fumarate. A strain of Bacillus (B11c) is shown to catabolize homogentisate via a previously undescribed version of the above sequence: homogentisate is cleaved by a 1,2-dioxygenase (E.C 1.13.11.5) yielding maleylacetoacetate which is hydrolyzed directly to acetoacetate and maleate."} {"id": "PMID:1260532", "title": "Toxigenic species of Penicillium, Fusarium, and Aspergillus from weevil-damaged pecans.", "content": "Of a total of 2392 fungi isolated from weevil-damaged pecans, 46.4% were Alternaria and Epicoccum, 23.9% were Penicillium, 12.4% were Pestalotia and Monochaeta, 6.5% were Cladosporium, 6.4% were Fusarium, and less than 2% each were Phoma, Aspergillus, Rhizopus, Trichothecium, and miscellaneous. Chloroform extracts of 34 of 105 representative Penicillium isolates, 3 of 28 Fusarium isolates, and 3 of 23 Aspergillus isolates were toxic to day-old cockerels during three bioassays. Eight of the toxic extracts from Penicillium spp. were tremorgenic. One tremorgenic isolate was identified as P. paxilli, four were identified as P. lanoso-coeruleum, and three as P. cyclopium. Nine of the non-tremorgenic isolates were identified as P. citrinum, five as P. aurantio-virens, three as P. oxalicum, and two as P. meleagrinum. Others were identified as one each of P. brevi-compactum (Series), P. nigricans (Series), P. roqueforti, P. rugulosum (Series), P. terrestre, and P. stoloniferium. One was unidentified. Toxigenic Aspergillus isolates were all A. flavus. Two of the toxic Fusarium isolates were F. moniliforme, and one was unidentified.", "contents": "Toxigenic species of Penicillium, Fusarium, and Aspergillus from weevil-damaged pecans. Of a total of 2392 fungi isolated from weevil-damaged pecans, 46.4% were Alternaria and Epicoccum, 23.9% were Penicillium, 12.4% were Pestalotia and Monochaeta, 6.5% were Cladosporium, 6.4% were Fusarium, and less than 2% each were Phoma, Aspergillus, Rhizopus, Trichothecium, and miscellaneous. Chloroform extracts of 34 of 105 representative Penicillium isolates, 3 of 28 Fusarium isolates, and 3 of 23 Aspergillus isolates were toxic to day-old cockerels during three bioassays. Eight of the toxic extracts from Penicillium spp. were tremorgenic. One tremorgenic isolate was identified as P. paxilli, four were identified as P. lanoso-coeruleum, and three as P. cyclopium. Nine of the non-tremorgenic isolates were identified as P. citrinum, five as P. aurantio-virens, three as P. oxalicum, and two as P. meleagrinum. Others were identified as one each of P. brevi-compactum (Series), P. nigricans (Series), P. roqueforti, P. rugulosum (Series), P. terrestre, and P. stoloniferium. One was unidentified. Toxigenic Aspergillus isolates were all A. flavus. Two of the toxic Fusarium isolates were F. moniliforme, and one was unidentified."} {"id": "PMID:1260533", "title": "Resistance of Thiobacillus novellus to mitomycin C and rifampicin.", "content": "Thiobacillus novellus is highly resistant to mitomycin C and rifampicin. This resistance is not due to insusceptibility of the target molecules to the drugs, since mitomycin C cross-links the DNA and rifampicin inhibits the DNA-dependent RNA polymerase of T. novellus in vitro.", "contents": "Resistance of Thiobacillus novellus to mitomycin C and rifampicin. Thiobacillus novellus is highly resistant to mitomycin C and rifampicin. This resistance is not due to insusceptibility of the target molecules to the drugs, since mitomycin C cross-links the DNA and rifampicin inhibits the DNA-dependent RNA polymerase of T. novellus in vitro."} {"id": "PMID:1260534", "title": "Comparison of the cell envelope proteins of Micrococcus cryophilus with those of Neisseria dnd Branhamella species.", "content": "In an attempt to elucidate the relation between Micrococcus cryophilus, Neisseria caviae, Neisseria ovis, and Branhamella catarrhalis, fractions derived from outer membranes of a strain of each organism were examined for protein composition by SDS - polyacrylamide gel electrophoresis. Micrococcus cryophilus outer membrane protein showed extensive similarities to that of N. ovis and contained a heat-modifiable protein which behaved almost identically with the corresponding bands previously shown to exist in N. caviae and N. ovis. Branhamella catarrhalis protein was distinctly different from those of M. cryophilus and the two 'false neisserias' N. caviae and N. ovis.", "contents": "Comparison of the cell envelope proteins of Micrococcus cryophilus with those of Neisseria dnd Branhamella species. In an attempt to elucidate the relation between Micrococcus cryophilus, Neisseria caviae, Neisseria ovis, and Branhamella catarrhalis, fractions derived from outer membranes of a strain of each organism were examined for protein composition by SDS - polyacrylamide gel electrophoresis. Micrococcus cryophilus outer membrane protein showed extensive similarities to that of N. ovis and contained a heat-modifiable protein which behaved almost identically with the corresponding bands previously shown to exist in N. caviae and N. ovis. Branhamella catarrhalis protein was distinctly different from those of M. cryophilus and the two 'false neisserias' N. caviae and N. ovis."} {"id": "PMID:1260535", "title": "beta-Xylosidases in the yeast Cryptococcus albidus var. aerius.", "content": "beta-xylosidase activity has been detected in cell-free extracts and in culture fluids when Cryptococcus albidus var. aerius was grown on glucose as the sole carbon source. The enzyme appears to be constitutive. Mild acid treatment of whole cells suggested that the total activity is located in the periplasmic space and some experiments indicated that it is partially associated with the cell walls. DEAE-Sephadex A50 chromatography has shown that there are two different forms of beta-xylosidase in the cell-free extracts, but only one form is present in the supernatants of culture.", "contents": "beta-Xylosidases in the yeast Cryptococcus albidus var. aerius. beta-xylosidase activity has been detected in cell-free extracts and in culture fluids when Cryptococcus albidus var. aerius was grown on glucose as the sole carbon source. The enzyme appears to be constitutive. Mild acid treatment of whole cells suggested that the total activity is located in the periplasmic space and some experiments indicated that it is partially associated with the cell walls. DEAE-Sephadex A50 chromatography has shown that there are two different forms of beta-xylosidase in the cell-free extracts, but only one form is present in the supernatants of culture."} {"id": "PMID:1260536", "title": "The isolation of Vibrio parahaemolyticus and related vibrios from moribund aquarium lobsters.", "content": "Vibrios were isolated in pure culture from the hemolymph of 7 out of 28 dead or dying aquarium lobsters which had been acclimated to 20-22 degrees C. One isolate was identified as Vibrio parahaemolyticus, one as a related marine Vibrio (probably V. marinus), and five as Vibrio alginolyticus. No isolates of halophilic Vibrio species were made from healthy lobsters using thiosulfate citrate bile salts sucrose agar (TCBS).", "contents": "The isolation of Vibrio parahaemolyticus and related vibrios from moribund aquarium lobsters. Vibrios were isolated in pure culture from the hemolymph of 7 out of 28 dead or dying aquarium lobsters which had been acclimated to 20-22 degrees C. One isolate was identified as Vibrio parahaemolyticus, one as a related marine Vibrio (probably V. marinus), and five as Vibrio alginolyticus. No isolates of halophilic Vibrio species were made from healthy lobsters using thiosulfate citrate bile salts sucrose agar (TCBS)."} {"id": "PMID:1260537", "title": "Temperature optima for bacteria and yeasts from cold-mountain habitats.", "content": "Optimal temperatures for the growth of bacteria and yeasts isolated from several cold-mountain habitats were determined. The lowest optimal temperatures encountered were in the 10-15 degrees C range, even though most of the isolates were obtained from sites at or near 0 degrees C.", "contents": "Temperature optima for bacteria and yeasts from cold-mountain habitats. Optimal temperatures for the growth of bacteria and yeasts isolated from several cold-mountain habitats were determined. The lowest optimal temperatures encountered were in the 10-15 degrees C range, even though most of the isolates were obtained from sites at or near 0 degrees C."} {"id": "PMID:1260538", "title": "Frothy feedlot bloat in cattle: production of extracellular polysaccharides and development of viscosity in cultures of Streptococcus bovis.", "content": "Streptococcus bovis was cultured in a synthetic medium with three concentrations of sucrose. Initial viscosity of the media was 1.5 centipoise (cp). After incubation for 8 h, the viscosity of the medium with 0.5% sucrose was unchanged, that with 3% sucrose had increased to 8 cp, and that with 6% sucrose to 112 cp. Similar results were found with a rumen fluid medium. A slimy material, responsible for increased viscosity of these cultures, was digested by dextranase. The material appeared as a complex system of intercellular fibers when viewed under the electron microscope after freeze-etching. With proteins and other polymers released from lysed bacteria, this slimy material may contribute directly to increased viscosity and foam formation. In addition to these intercellular fibers, each cell was surrounded by a fibrous capsule that was not digested by dextranase. This capsule stained with lead citrate and uranyl acetate, but not with ruthenium red. The amount of capsular material produced was similar whether the media contained 0.5, 3.0, or 6% sucrose.", "contents": "Frothy feedlot bloat in cattle: production of extracellular polysaccharides and development of viscosity in cultures of Streptococcus bovis. Streptococcus bovis was cultured in a synthetic medium with three concentrations of sucrose. Initial viscosity of the media was 1.5 centipoise (cp). After incubation for 8 h, the viscosity of the medium with 0.5% sucrose was unchanged, that with 3% sucrose had increased to 8 cp, and that with 6% sucrose to 112 cp. Similar results were found with a rumen fluid medium. A slimy material, responsible for increased viscosity of these cultures, was digested by dextranase. The material appeared as a complex system of intercellular fibers when viewed under the electron microscope after freeze-etching. With proteins and other polymers released from lysed bacteria, this slimy material may contribute directly to increased viscosity and foam formation. In addition to these intercellular fibers, each cell was surrounded by a fibrous capsule that was not digested by dextranase. This capsule stained with lead citrate and uranyl acetate, but not with ruthenium red. The amount of capsular material produced was similar whether the media contained 0.5, 3.0, or 6% sucrose."} {"id": "PMID:1260539", "title": "Studies on the cellular and free lipopolysaccharides from Branhamella catarrhalis.", "content": "Cellular and free lipopolysaccharides obtained from Neisseria catarrhalis and Branhamella catarrhalis were found to be essentially identical. Both cellular and free lipopolysaccharides contained core-oligosaccharides of the following composition: D-glucose (4 mol), D-galactose (1 mol), 2-amino-2-deoxy-D-glucose (1 mol), and 3-deoxy-D-manno-octulosonic acid. Aldoheptose and phosphate components were below levels of detection. Several physical methods indicated that all core-oligosaccharide preparations were identical. Lipid A preparations from cellular and free lipopolysaccharides of both organisms were qualitatively and quantitatively similar; they were composed of decanoic acid, dodecanoic acid, 3-hydroxy dodecanoic acid, 2-amino-2-deoxy-D-glucose, phosphate, and ethanolamine. The results tend to justify the transfer of Neisseria catarrhalis to the genus Branhamella.", "contents": "Studies on the cellular and free lipopolysaccharides from Branhamella catarrhalis. Cellular and free lipopolysaccharides obtained from Neisseria catarrhalis and Branhamella catarrhalis were found to be essentially identical. Both cellular and free lipopolysaccharides contained core-oligosaccharides of the following composition: D-glucose (4 mol), D-galactose (1 mol), 2-amino-2-deoxy-D-glucose (1 mol), and 3-deoxy-D-manno-octulosonic acid. Aldoheptose and phosphate components were below levels of detection. Several physical methods indicated that all core-oligosaccharide preparations were identical. Lipid A preparations from cellular and free lipopolysaccharides of both organisms were qualitatively and quantitatively similar; they were composed of decanoic acid, dodecanoic acid, 3-hydroxy dodecanoic acid, 2-amino-2-deoxy-D-glucose, phosphate, and ethanolamine. The results tend to justify the transfer of Neisseria catarrhalis to the genus Branhamella."} {"id": "PMID:1260540", "title": "Effect of calcium and anaerobiosis on the thermostability of Bacillus stearothermophilus.", "content": "Bacillus stearothermophilus NCA 2184 lost viability and subsequently released cytoplasmic components when suspended in 0.1 M tris(hydroxymethyl)aminomethane (Tris) buffer (pH 7.2) and incubated at 60 degrees C. Cell lysis was prevented by the addition of 10 mM CaCl2 to the Tris-buffer suspension. Cells which were incubated under anaerobic conditions for 20 min in the growth medium before they were collected were stable in the Tris-buffer suspension without added calcium. Anaerobic incubation effected an increase in membrane cardiolipin which appeared to be related to the increase in the thermostability of the cells.", "contents": "Effect of calcium and anaerobiosis on the thermostability of Bacillus stearothermophilus. Bacillus stearothermophilus NCA 2184 lost viability and subsequently released cytoplasmic components when suspended in 0.1 M tris(hydroxymethyl)aminomethane (Tris) buffer (pH 7.2) and incubated at 60 degrees C. Cell lysis was prevented by the addition of 10 mM CaCl2 to the Tris-buffer suspension. Cells which were incubated under anaerobic conditions for 20 min in the growth medium before they were collected were stable in the Tris-buffer suspension without added calcium. Anaerobic incubation effected an increase in membrane cardiolipin which appeared to be related to the increase in the thermostability of the cells."} {"id": "PMID:1260542", "title": "Somatic nuclear division in the sporidia of Ustilago violacea. III. Ultrastructural observations.", "content": "The paper provides detailed ultrastructural observations on nuclear division in the smut fungus Ustilago violacea and is based on previous light-microscopic work outlining the division in living and stained cells. The division as in many other Basidiomycetes is not intranuclear, but occurs within a partially disrupted membrane. The division takes place after migration of most of the nucleus into the bud cell, after limited breakdown of the nuclear membrane, and after the formation of a spindle between two spindle-pole bodies (SPB). The remaining part of the nucleus containing the nucleolus is left behind in the parent cell and degenerates there. The SPB, as in other Basidiomycetes, is a dome-shaped relatively structureless body, quite distinct from the flat plaques of many Ascomycetes and the elaborat centrioles of Phycomycetes. The SPB divides shortly before migration into the daughter cell and invariably is located at the apex of the migrating nucleus. Nuclear division is completed when the two masses of chromatin clustered about each of the SPB's are separated as the spindle elongates. One daughter neculeus reforms in the bud and the other is reformed in the mother cell. Cells fixed and stained by conventional light-microscopic methods were examined in the light of the electron-microscopic observations to determine whether these procedures induce artefacts. Aceto-orcein and Giemsa when used cold were found to produce relatively artefact-free preparations. However, previous results in which the cells were warmed gently in these stains are now seen to contain artefacts in the form of contracted chromatinic granules often arranged in chains. These artefacts may provide useful information but clearly they must be interpreted cautiously until the nature of the changes induced by heating are known.", "contents": "Somatic nuclear division in the sporidia of Ustilago violacea. III. Ultrastructural observations. The paper provides detailed ultrastructural observations on nuclear division in the smut fungus Ustilago violacea and is based on previous light-microscopic work outlining the division in living and stained cells. The division as in many other Basidiomycetes is not intranuclear, but occurs within a partially disrupted membrane. The division takes place after migration of most of the nucleus into the bud cell, after limited breakdown of the nuclear membrane, and after the formation of a spindle between two spindle-pole bodies (SPB). The remaining part of the nucleus containing the nucleolus is left behind in the parent cell and degenerates there. The SPB, as in other Basidiomycetes, is a dome-shaped relatively structureless body, quite distinct from the flat plaques of many Ascomycetes and the elaborat centrioles of Phycomycetes. The SPB divides shortly before migration into the daughter cell and invariably is located at the apex of the migrating nucleus. Nuclear division is completed when the two masses of chromatin clustered about each of the SPB's are separated as the spindle elongates. One daughter neculeus reforms in the bud and the other is reformed in the mother cell. Cells fixed and stained by conventional light-microscopic methods were examined in the light of the electron-microscopic observations to determine whether these procedures induce artefacts. Aceto-orcein and Giemsa when used cold were found to produce relatively artefact-free preparations. However, previous results in which the cells were warmed gently in these stains are now seen to contain artefacts in the form of contracted chromatinic granules often arranged in chains. These artefacts may provide useful information but clearly they must be interpreted cautiously until the nature of the changes induced by heating are known."} {"id": "PMID:1260543", "title": "Somatic nuclear division in the sporidia of Ustilago violacea. IV. Microtubules and the spindle-pole body.", "content": "In unbudded cells of the anther smut fungus Ustilago violacea there is a dome-shaped spindle-pole body (SPB) consisting of a core 0.1 mum in diameter surrounded by a ribosome-free region 0.3-0.4 mum in diameter lying in a pocket of the nuclear membrane. After budding the nucleus moves towards the bud and begins to rotate rapidly. At about this stage the SPB divides into two parallel bars each about 0.1-0.15 mum in diameter and 0.3 mum long, separated by a distance of about 0.3 mum. Microtubules associated with the nuclear membrane but not with the SPB are present at the time of nuclear rotation. These microtubules disappear when rotation stops. Microtubules attached to the SPB are found during migration of the chromatinic portion of the nucleus into the bud cell. These microtubules disappear when migration stops and the nuclear membrand begins to break down. The twin SPB bars appear to move into the nucleus through a break in the membrane and begin to move apart forming a spindle about 1 mum long. Chromosomal microtubules (one per kinetochore) were found in several serial sections, and in addition there appeared to be several continuous microtubules present. The separation of the two chromatinic masses appeared to result from elongation of the continuous microtubules to about 3 mum long. Cytoplasmic microtubules and spindle microtubules were both found attached to the SPB as it elongated and one nucleus returned to the mother cell. The paper concludes with a discussion of the SPB as a multifuncitonal control center affecting nuclear migration, spindle formation, membrane breakdown and synthesis, karyogamy, conjugation, budding, chromosomal movement, replication, and disjunction.", "contents": "Somatic nuclear division in the sporidia of Ustilago violacea. IV. Microtubules and the spindle-pole body. In unbudded cells of the anther smut fungus Ustilago violacea there is a dome-shaped spindle-pole body (SPB) consisting of a core 0.1 mum in diameter surrounded by a ribosome-free region 0.3-0.4 mum in diameter lying in a pocket of the nuclear membrane. After budding the nucleus moves towards the bud and begins to rotate rapidly. At about this stage the SPB divides into two parallel bars each about 0.1-0.15 mum in diameter and 0.3 mum long, separated by a distance of about 0.3 mum. Microtubules associated with the nuclear membrane but not with the SPB are present at the time of nuclear rotation. These microtubules disappear when rotation stops. Microtubules attached to the SPB are found during migration of the chromatinic portion of the nucleus into the bud cell. These microtubules disappear when migration stops and the nuclear membrand begins to break down. The twin SPB bars appear to move into the nucleus through a break in the membrane and begin to move apart forming a spindle about 1 mum long. Chromosomal microtubules (one per kinetochore) were found in several serial sections, and in addition there appeared to be several continuous microtubules present. The separation of the two chromatinic masses appeared to result from elongation of the continuous microtubules to about 3 mum long. Cytoplasmic microtubules and spindle microtubules were both found attached to the SPB as it elongated and one nucleus returned to the mother cell. The paper concludes with a discussion of the SPB as a multifuncitonal control center affecting nuclear migration, spindle formation, membrane breakdown and synthesis, karyogamy, conjugation, budding, chromosomal movement, replication, and disjunction."} {"id": "PMID:1260544", "title": "Nitrogen fixation associated with grasses in Oregon.", "content": "Nitrogen fixation associated with both natural grasslands and grain crops of Oregon was studied using the acetylene-reduction assay. A number of the grasses collected has some acetylene-reducing activity. Agrostis tenuis Sibth. had substantially greater activity than any of the other species, with a mean rate estimated at 37 g N2 fixed per hectare per day. Assuming 100 days of activity, about 3 kg of N2 would be fixed per hectare per year. This quantity of nitrogen may be important in the maintenance of this species under natural conditions. Nitrogen-fixing microorganisms were isolated from the root surfaces of some of the grasses. Cultures of Bacillus macerans, Bacillus polymyxa, and Enterobacter cloacoa were isolated from wheat roots as were two cultures which have not been assigned a specific taxonomic classification. Strains of N2-fixing Bacillus species and Gram-negative aerobic bacteria were isolated from Festuca and Agrostis.", "contents": "Nitrogen fixation associated with grasses in Oregon. Nitrogen fixation associated with both natural grasslands and grain crops of Oregon was studied using the acetylene-reduction assay. A number of the grasses collected has some acetylene-reducing activity. Agrostis tenuis Sibth. had substantially greater activity than any of the other species, with a mean rate estimated at 37 g N2 fixed per hectare per day. Assuming 100 days of activity, about 3 kg of N2 would be fixed per hectare per year. This quantity of nitrogen may be important in the maintenance of this species under natural conditions. Nitrogen-fixing microorganisms were isolated from the root surfaces of some of the grasses. Cultures of Bacillus macerans, Bacillus polymyxa, and Enterobacter cloacoa were isolated from wheat roots as were two cultures which have not been assigned a specific taxonomic classification. Strains of N2-fixing Bacillus species and Gram-negative aerobic bacteria were isolated from Festuca and Agrostis."} {"id": "PMID:1260545", "title": "Effect of hydroxamic acids on growth and urease activity in Corynebacterium renale.", "content": "Studies were conducted on the effect of four different hydroxamic acids (HA), hydroxyurea, acetohydroxamic acid, p-flurobenzoylhydroxamic acid and sorbylhydroxamic acid, on the growth and urease activity of Corynebacterium renale. The addition of each of these HA, at concentrations ranging form 10(-3) to 10(-5) M, to medium containing urea as the sole nitrogen source resulted in a lengthened lag period of growth the extent of which depended upon the concentration of each HA tested as well as the structure of the compound; that is, the size and (or) complexity of the side chain attached to the common terminal group of the molecule. However, the maximal growth levels achieved following conclusion of the exponential phase were not affected by the HA. Investigations on the effect of these HA on the urease activity of intact cells as well as cell-free extracts revealed that in each case the enzymatic activity was inhibited by each of the HA tested. The extent of inhibition with the intact cells was aobut one-half of that observed with cell-free extracts. Direct incubation of cell-free extracts as well as intact cells with each of the HA tested was required for maximal inhibition.", "contents": "Effect of hydroxamic acids on growth and urease activity in Corynebacterium renale. Studies were conducted on the effect of four different hydroxamic acids (HA), hydroxyurea, acetohydroxamic acid, p-flurobenzoylhydroxamic acid and sorbylhydroxamic acid, on the growth and urease activity of Corynebacterium renale. The addition of each of these HA, at concentrations ranging form 10(-3) to 10(-5) M, to medium containing urea as the sole nitrogen source resulted in a lengthened lag period of growth the extent of which depended upon the concentration of each HA tested as well as the structure of the compound; that is, the size and (or) complexity of the side chain attached to the common terminal group of the molecule. However, the maximal growth levels achieved following conclusion of the exponential phase were not affected by the HA. Investigations on the effect of these HA on the urease activity of intact cells as well as cell-free extracts revealed that in each case the enzymatic activity was inhibited by each of the HA tested. The extent of inhibition with the intact cells was aobut one-half of that observed with cell-free extracts. Direct incubation of cell-free extracts as well as intact cells with each of the HA tested was required for maximal inhibition."} {"id": "PMID:1260546", "title": "Temperature-induced alterations in phospholipids of Fusarium oxysporum f. sp. lycopersici.", "content": "Ten phospholipids were identified in hyphal membrane preparations of Fusarium oxysporum f. sp. lycopersici when the cells were grown to the late log phase at 15, 25, and 37 degrees C, respectively. The major phospholipids present were phosphatidylcholine (PC) and phosphatidylethanolamine (PE), which together made up about 70% of the total membrane phospholipids. The degree of unsaturation in the acyl group of the phospholipids was inversely related to growth temperature. The polar head group composition was also affected by growth temperature. Cells grown at 15 and 25 degrees C contained the same relative proportions of PC and PE, but when the growth temperature was raised to 37 degrees C, the ratio of PC to PE was doubled. A methylating system capable of converting PE to PC was demonstrated in vitro.", "contents": "Temperature-induced alterations in phospholipids of Fusarium oxysporum f. sp. lycopersici. Ten phospholipids were identified in hyphal membrane preparations of Fusarium oxysporum f. sp. lycopersici when the cells were grown to the late log phase at 15, 25, and 37 degrees C, respectively. The major phospholipids present were phosphatidylcholine (PC) and phosphatidylethanolamine (PE), which together made up about 70% of the total membrane phospholipids. The degree of unsaturation in the acyl group of the phospholipids was inversely related to growth temperature. The polar head group composition was also affected by growth temperature. Cells grown at 15 and 25 degrees C contained the same relative proportions of PC and PE, but when the growth temperature was raised to 37 degrees C, the ratio of PC to PE was doubled. A methylating system capable of converting PE to PC was demonstrated in vitro."} {"id": "PMID:1260547", "title": "Immediate postnatal decontamination as a means of obtaining axenic animals and human infants.", "content": "A technique not involving surgery is described for obtaining axenic (germ-free) newborn animals and human infants by decontamination immediately after birth. Three steps are involved: cleansing ther perineal region of the mother with an iodinated bactericidal solution, washing the newborn with the same solution, and after the newborn has been placed in a sterile isolater, administering a single oral dose of an antibiotic mixture previously determined to be active against the fecal and vaginal flora of the mother. All of the newborn obtained by means of this technique, including 13 piglets, 2 lambs, and 4 human infants, were found to be axenic throughout their stay in the isolators. Four piglets obtained by the same technique, but without adminstration of antibiotic mixture, were found not to be anenic. This technique, as compared with methods of surgical delivery of axenic young, embodies a number of advantages. It is harmless to the mother and to the newborn, it is relatively inexpensive, and it obviates the risk of prematurity involved in elective surgical delivery before term.", "contents": "Immediate postnatal decontamination as a means of obtaining axenic animals and human infants. A technique not involving surgery is described for obtaining axenic (germ-free) newborn animals and human infants by decontamination immediately after birth. Three steps are involved: cleansing ther perineal region of the mother with an iodinated bactericidal solution, washing the newborn with the same solution, and after the newborn has been placed in a sterile isolater, administering a single oral dose of an antibiotic mixture previously determined to be active against the fecal and vaginal flora of the mother. All of the newborn obtained by means of this technique, including 13 piglets, 2 lambs, and 4 human infants, were found to be axenic throughout their stay in the isolators. Four piglets obtained by the same technique, but without adminstration of antibiotic mixture, were found not to be anenic. This technique, as compared with methods of surgical delivery of axenic young, embodies a number of advantages. It is harmless to the mother and to the newborn, it is relatively inexpensive, and it obviates the risk of prematurity involved in elective surgical delivery before term."} {"id": "PMID:1260548", "title": "Halobacterium saccharovorum sp. nov., a carbohydrate-metabolizing, extremely halophilic bacterium.", "content": "The previously described extremely halophilic bacterium, strain M6, metabolizes a variety of carbohydrates with the production of acid. In addition, the organism produces nitrite (but no gas) from nitrate, is motile, and grows most rapidly at about 50 degrees C. These characteristics distinguish it from all previously described halophilic bacteria in the genus Halobacterium. It is suggested that it be designated as a new species, Halobacterium saccharovorum.", "contents": "Halobacterium saccharovorum sp. nov., a carbohydrate-metabolizing, extremely halophilic bacterium. The previously described extremely halophilic bacterium, strain M6, metabolizes a variety of carbohydrates with the production of acid. In addition, the organism produces nitrite (but no gas) from nitrate, is motile, and grows most rapidly at about 50 degrees C. These characteristics distinguish it from all previously described halophilic bacteria in the genus Halobacterium. It is suggested that it be designated as a new species, Halobacterium saccharovorum."} {"id": "PMID:1260549", "title": "Comparison of biodegradability of crude and fuel oils.", "content": "Crude and fuel oils were compared for ability to support growth of a mixed population of estuarine bacteria. A total of four oils, two crude and two fuel oils, were examined. It was found that each of the oils supported a unique population of bacteria and yeasts, with respect to generic composition. Low-sulfur, high-saturate, South Louisiana crude oil was found to be highly susceptible to degradation. In contrast, the dense, high-sulfur, high-aromatic, Bunker C fuel oil was strongly refractory to microbial degradation.", "contents": "Comparison of biodegradability of crude and fuel oils. Crude and fuel oils were compared for ability to support growth of a mixed population of estuarine bacteria. A total of four oils, two crude and two fuel oils, were examined. It was found that each of the oils supported a unique population of bacteria and yeasts, with respect to generic composition. Low-sulfur, high-saturate, South Louisiana crude oil was found to be highly susceptible to degradation. In contrast, the dense, high-sulfur, high-aromatic, Bunker C fuel oil was strongly refractory to microbial degradation."} {"id": "PMID:1260550", "title": "Use of a membrane oxygenator for open-heart surgery in infants.", "content": "Because use of the bubble oxygenator during open-heart surgery is associated with complications such as hemolysis, pulmonary insufficiency and oliguria, a membrane oxygenator was used in conjunction with hypothermia in 37 infants. The main features of the oxygenator are gravitational blood flow, oxygenation into an airless, collapsible blood reservoir, low-flow roller pump flow back to the patient, accurate determination of flows and careful use of a heat exchanger. Gas flow (98% oxygen, 2% carbon dioxide) for the unit of 2 m2 is maintained at 3 to 4 1/min. Specific precautions are taken to ensure absence of bubbles. Three prime solutions are used, the final one having an osmolality of 381 mOsmol and containing 129.9 meq of sodium, 3.8 of potassium and 94.0 of chloride and 2001 mg/dl of glucose. Six patients died, but none of the deaths could be directly related to the use of the oxygenator. Respiratory complications were minimal, as were other complications. The technique is reliable in oxygenating blood in an tracorporeal circulation, but further familiarity with the membrane oxygenator for use in open-heart surgery in infants is desirable before firm conclusions can be drawn as to its value.", "contents": "Use of a membrane oxygenator for open-heart surgery in infants. Because use of the bubble oxygenator during open-heart surgery is associated with complications such as hemolysis, pulmonary insufficiency and oliguria, a membrane oxygenator was used in conjunction with hypothermia in 37 infants. The main features of the oxygenator are gravitational blood flow, oxygenation into an airless, collapsible blood reservoir, low-flow roller pump flow back to the patient, accurate determination of flows and careful use of a heat exchanger. Gas flow (98% oxygen, 2% carbon dioxide) for the unit of 2 m2 is maintained at 3 to 4 1/min. Specific precautions are taken to ensure absence of bubbles. Three prime solutions are used, the final one having an osmolality of 381 mOsmol and containing 129.9 meq of sodium, 3.8 of potassium and 94.0 of chloride and 2001 mg/dl of glucose. Six patients died, but none of the deaths could be directly related to the use of the oxygenator. Respiratory complications were minimal, as were other complications. The technique is reliable in oxygenating blood in an tracorporeal circulation, but further familiarity with the membrane oxygenator for use in open-heart surgery in infants is desirable before firm conclusions can be drawn as to its value."} {"id": "PMID:1260551", "title": "Pericardiectomy for uremic tamponade.", "content": "Pericardial tamponade developed in 29 patients with uremia. The clinical presentation varied, some patients having no symptoms whereas others sustained circulatory collapse. Pericardial friction rub, elevated central venous pressure and a paradoxical pulse were the most common physical findings. Serial chest radiography and echocardiography were most useful procedures in confirming this diagnosis. Two patients were treated conservatively and died despite repeated pericardiocentesis. The remaining 27 patients underwent partial pericardiectomy. One patient died of cardiorespiratory failure and a second from brain damage related to cardiac arrest before pericardiectomy. The other 25 patients reported immediate relief of symptoms and no recurrence of pericarditis. Pericardiectomy is the treatment of choice in uremic pericardial tamponade.", "contents": "Pericardiectomy for uremic tamponade. Pericardial tamponade developed in 29 patients with uremia. The clinical presentation varied, some patients having no symptoms whereas others sustained circulatory collapse. Pericardial friction rub, elevated central venous pressure and a paradoxical pulse were the most common physical findings. Serial chest radiography and echocardiography were most useful procedures in confirming this diagnosis. Two patients were treated conservatively and died despite repeated pericardiocentesis. The remaining 27 patients underwent partial pericardiectomy. One patient died of cardiorespiratory failure and a second from brain damage related to cardiac arrest before pericardiectomy. The other 25 patients reported immediate relief of symptoms and no recurrence of pericarditis. Pericardiectomy is the treatment of choice in uremic pericardial tamponade."} {"id": "PMID:1260552", "title": "A new model for assessment of myocardial function: I. Description and performance norms.", "content": "Use of a new isometric rabbit-heart model, a modification of Langer's original preparation, has permitted independent assessment of myocardial perfusability in addition to contractility and relaxation. In this model an isolated, paced, interventricular septum contracts against a tension transducer and is perfused from another awake rabbit. Heparinized, diluted arterial blood is warmed and pumped at 1 ml/g-min. Perfusion pressure is measured by transducer. Each preparation serves as its own control. This model was used in determining performance norms for 68 preparations. Contractility was measured by maximum active tension, maximum rate of increase of tension and time to peak tension; relaxation by resting tension, maximum rate of relaxation and relaxation time; and perfusability by mean perfusion pressure and mean conductance. The status of the parabiotic rabbit was closely monitored. These studies have shown that the model is relatively simple, clearly defined and adaptable to a variety of experimental protocols.", "contents": "A new model for assessment of myocardial function: I. Description and performance norms. Use of a new isometric rabbit-heart model, a modification of Langer's original preparation, has permitted independent assessment of myocardial perfusability in addition to contractility and relaxation. In this model an isolated, paced, interventricular septum contracts against a tension transducer and is perfused from another awake rabbit. Heparinized, diluted arterial blood is warmed and pumped at 1 ml/g-min. Perfusion pressure is measured by transducer. Each preparation serves as its own control. This model was used in determining performance norms for 68 preparations. Contractility was measured by maximum active tension, maximum rate of increase of tension and time to peak tension; relaxation by resting tension, maximum rate of relaxation and relaxation time; and perfusability by mean perfusion pressure and mean conductance. The status of the parabiotic rabbit was closely monitored. These studies have shown that the model is relatively simple, clearly defined and adaptable to a variety of experimental protocols."} {"id": "PMID:1260553", "title": "Intra-aortic balloon pump assist: adjunct to surgery for left ventricular dysfunction.", "content": "Intra-aortic balloon pump assist (IABPA) was used intraoperatively and postoperatively in 34 patients with severe left ventricular dysfunction: the mean ejection fraction was 0.29 and all patients had angiographic grade IV left ventricular contractility. There were three groups of patients: 11 patients with acute coronary artery insufficiency--10 of whom survived vein bypass surgery (group 1); 16 patients with crescendo-type unstable angina--of whom 15 survived surgery (group 2); 7 patients with single (6) or multivalvular (1) replacement (combined with vein bypass in 3)--of whom 5 survived (group 3). Overall survival was 88%. The mean duration of 1:1 IABPA was 40 hours. Inotropic support was not required, hemolysis was insignificant and hemostasis remained secure. Two patients required tracheostomy and one required dialysis. One patient had a peripheral embolus in the leg used for IABPA. IABPA improves subendocardial perfusion during induction of anesthesia, during cardiopulmonary bypass and into the postoperative period; left ventricular work is decreased with a concomitant increase in coronary artery and vein graft blood flow. Use of IABPA may also improve survival and lessen morbidity in patients with left ventricular dysfunction due to the beneficial effects on myocardial performance and is thus a valuable adjunct to cardiac surgery in high-risk patients.", "contents": "Intra-aortic balloon pump assist: adjunct to surgery for left ventricular dysfunction. Intra-aortic balloon pump assist (IABPA) was used intraoperatively and postoperatively in 34 patients with severe left ventricular dysfunction: the mean ejection fraction was 0.29 and all patients had angiographic grade IV left ventricular contractility. There were three groups of patients: 11 patients with acute coronary artery insufficiency--10 of whom survived vein bypass surgery (group 1); 16 patients with crescendo-type unstable angina--of whom 15 survived surgery (group 2); 7 patients with single (6) or multivalvular (1) replacement (combined with vein bypass in 3)--of whom 5 survived (group 3). Overall survival was 88%. The mean duration of 1:1 IABPA was 40 hours. Inotropic support was not required, hemolysis was insignificant and hemostasis remained secure. Two patients required tracheostomy and one required dialysis. One patient had a peripheral embolus in the leg used for IABPA. IABPA improves subendocardial perfusion during induction of anesthesia, during cardiopulmonary bypass and into the postoperative period; left ventricular work is decreased with a concomitant increase in coronary artery and vein graft blood flow. Use of IABPA may also improve survival and lessen morbidity in patients with left ventricular dysfunction due to the beneficial effects on myocardial performance and is thus a valuable adjunct to cardiac surgery in high-risk patients."} {"id": "PMID:1260554", "title": "Surgical repair of acute ventricular spetal defect complicating myocardical infarction.", "content": "Ventricular septal defect complicating myocardial infarction was repaired surgically in seven patients between 1965 and 1974. In four, the septal defect had developed in the lower portion of the septum and in three, high in the septum, above the origin of the papillary muscle. Concomitant operations included mitral valve replacement and infarctectomy, in one patient, and triple aortocoronary bypass in another. The commoner low defect was repaired either by amputating the lower portion of the heart or patch-repairing through a left ventriculotomy incision. The higher defects, more difficult to repair, were repaired through a high posterior left ventriculotomy. Complete pre- and postoperative hemodynamic studies were carried out and follow-up information was available for all patients. Recognition of the high defect is essential. Pathologically, the coronary artery lesion is more complicated and extensive and a different surgical approach is necessary. A classification of high and low ventricular septal defects developing after myocardial infarction is recommeneded. The natural history of the disease and the reasonable surgical results support an active surgical approach in both types of postinfarction septal perforation.", "contents": "Surgical repair of acute ventricular spetal defect complicating myocardical infarction. Ventricular septal defect complicating myocardial infarction was repaired surgically in seven patients between 1965 and 1974. In four, the septal defect had developed in the lower portion of the septum and in three, high in the septum, above the origin of the papillary muscle. Concomitant operations included mitral valve replacement and infarctectomy, in one patient, and triple aortocoronary bypass in another. The commoner low defect was repaired either by amputating the lower portion of the heart or patch-repairing through a left ventriculotomy incision. The higher defects, more difficult to repair, were repaired through a high posterior left ventriculotomy. Complete pre- and postoperative hemodynamic studies were carried out and follow-up information was available for all patients. Recognition of the high defect is essential. Pathologically, the coronary artery lesion is more complicated and extensive and a different surgical approach is necessary. A classification of high and low ventricular septal defects developing after myocardial infarction is recommeneded. The natural history of the disease and the reasonable surgical results support an active surgical approach in both types of postinfarction septal perforation."} {"id": "PMID:1260555", "title": "Synovial chondrometaplasia: review of world literature and a study of 18 Canadian cases.", "content": "A retrospective study of synovial chondro-metaplasia in Canada revealed 18 well-documented cases of this condition. Review of these cases together with 137 cases obtained from the literature permitted clarification of the clinical, radiologic and histologic features of the clinical, radiologic and histologic features of the disease. Positive histologic proof of synovial chondrometaplasia is necessary for a true diagnosis. Synovectomy with excision of loose bodies is the treatment of choice in symptomatic cases.", "contents": "Synovial chondrometaplasia: review of world literature and a study of 18 Canadian cases. A retrospective study of synovial chondro-metaplasia in Canada revealed 18 well-documented cases of this condition. Review of these cases together with 137 cases obtained from the literature permitted clarification of the clinical, radiologic and histologic features of the clinical, radiologic and histologic features of the disease. Positive histologic proof of synovial chondrometaplasia is necessary for a true diagnosis. Synovectomy with excision of loose bodies is the treatment of choice in symptomatic cases."} {"id": "PMID:1260556", "title": "Familial polyposis coli and periampullary carcinoma.", "content": "An 80-year-old woman with periampullary carcinoma was found, at autopsy, to have polyposis coli. A brief review of the literature indicates that, although the association of Gardner's syndrome with duodenal and pancreatic carcinoma is well established, the patient described in this report is only the second with polyposis coli in whom a periampullary carcinoma developed.", "contents": "Familial polyposis coli and periampullary carcinoma. An 80-year-old woman with periampullary carcinoma was found, at autopsy, to have polyposis coli. A brief review of the literature indicates that, although the association of Gardner's syndrome with duodenal and pancreatic carcinoma is well established, the patient described in this report is only the second with polyposis coli in whom a periampullary carcinoma developed."} {"id": "PMID:1260557", "title": "Congenital hip dislocations diagnosed after walking age: results of treatment.", "content": "The results of treatment of 64 congenital hip dislocations, diagnosed after the children were of walking age, were assessed anatomically, using two criteria--general femoral head shape and the C.E. angle of Wiberg. Results were also related to age at diagnosis and treatment methods. Radiologically 62% of the hips had normal or good results, and of these, 82% were obtained when the diagnosis was made and treatment started before the age of 36 months. In this series no correlation existed between anatomical result and treatment method.", "contents": "Congenital hip dislocations diagnosed after walking age: results of treatment. The results of treatment of 64 congenital hip dislocations, diagnosed after the children were of walking age, were assessed anatomically, using two criteria--general femoral head shape and the C.E. angle of Wiberg. Results were also related to age at diagnosis and treatment methods. Radiologically 62% of the hips had normal or good results, and of these, 82% were obtained when the diagnosis was made and treatment started before the age of 36 months. In this series no correlation existed between anatomical result and treatment method."} {"id": "PMID:1260588", "title": "Cigarette smoking and the young: a national survey.", "content": "Cigarette smoking behaviour among the young was examined in the light of the responses of over 78 000 students to a 1972 questionnaire survey of Canadian schools. As few as 2% (8-year-old girls) and as many as 60% (16 year--old boys) were smoking one or more cigarettes per week. The prevalence of smoking was higher than that reported in earlier studies. Students, particularly girls, were beginning to smoke at progressively earlier ages. Some differences in smoking behaviour were found between regions, language groups and groups of children whose parents did or did not smoke. Recognition of immediate rather than long-term effects of smoking on health was reported as an important consideration in not smoking.", "contents": "Cigarette smoking and the young: a national survey. Cigarette smoking behaviour among the young was examined in the light of the responses of over 78 000 students to a 1972 questionnaire survey of Canadian schools. As few as 2% (8-year-old girls) and as many as 60% (16 year--old boys) were smoking one or more cigarettes per week. The prevalence of smoking was higher than that reported in earlier studies. Students, particularly girls, were beginning to smoke at progressively earlier ages. Some differences in smoking behaviour were found between regions, language groups and groups of children whose parents did or did not smoke. Recognition of immediate rather than long-term effects of smoking on health was reported as an important consideration in not smoking."} {"id": "PMID:1260589", "title": "Drug surveillance data in a Canadian hospital.", "content": "Comparison of results of a Canadian hospital-based drug surveillance program with data from centres in the United States and Israel showed no important difference in the rate of drug exposures or adverse reactions. Drugs for symptomatic relief were frequently used in the Canadian centre. Women received more drugs and had more adverse reactions than men. Life-threatening and potentially fatal reactions were caused by commonly used drugs; autopsy findings may detect previously unsuspected relations between drug events and mechanisms of death. Voluntary reporting and intensive monitoring are both important in the field of adverse drug reactions.", "contents": "Drug surveillance data in a Canadian hospital. Comparison of results of a Canadian hospital-based drug surveillance program with data from centres in the United States and Israel showed no important difference in the rate of drug exposures or adverse reactions. Drugs for symptomatic relief were frequently used in the Canadian centre. Women received more drugs and had more adverse reactions than men. Life-threatening and potentially fatal reactions were caused by commonly used drugs; autopsy findings may detect previously unsuspected relations between drug events and mechanisms of death. Voluntary reporting and intensive monitoring are both important in the field of adverse drug reactions."} {"id": "PMID:1260590", "title": "Experience with SI units in biochemistry.", "content": "Use of Syst\u00e8me International d'Unit\u00e9s (SI) for laboratory measurements was instituted Jan. 1, 1975 at two community hospitals. Beforehand, talks were given, pamphlets, conversion tables, new calibration curves and new master record cards were printed, computer cards were reprogrammed and conversion kits were prepared; the total cost was less than $200. After 6 months 16% of the medical staff had stopped converting SI units into conventional units, 78% were still occasionally converting units and 6% were routinely converting units. Changeover had been difficult for 25%, only a nuisance for 49% and easy for 26%. The patients' lives were not endangered by conversion.", "contents": "Experience with SI units in biochemistry. Use of Syst\u00e8me International d'Unit\u00e9s (SI) for laboratory measurements was instituted Jan. 1, 1975 at two community hospitals. Beforehand, talks were given, pamphlets, conversion tables, new calibration curves and new master record cards were printed, computer cards were reprogrammed and conversion kits were prepared; the total cost was less than $200. After 6 months 16% of the medical staff had stopped converting SI units into conventional units, 78% were still occasionally converting units and 6% were routinely converting units. Changeover had been difficult for 25%, only a nuisance for 49% and easy for 26%. The patients' lives were not endangered by conversion."} {"id": "PMID:1260602", "title": "Atypical mycobacteria in a tuberculosis hospital.", "content": "Cultures from 80 out of 1667 patients (4.8%) admitted consecutively to a tuberculosis hospital grew atypical mycobacteria. With four strict criteria it was concluded that the mycobacteria isolated were the cause of the disease in 47 of these patients. The majority of these organisms were resistant to most, and in seven cases to all, of the antituberculous drugs. Ten patients responded poorly to treatment and 14 patients (30%) died, 8 of these from uncontrollable pulmonary infection with the atypical organisms. It is suggested that a recent, simplified classification of mycobacteria proposed by Runyon be adopted.", "contents": "Atypical mycobacteria in a tuberculosis hospital. Cultures from 80 out of 1667 patients (4.8%) admitted consecutively to a tuberculosis hospital grew atypical mycobacteria. With four strict criteria it was concluded that the mycobacteria isolated were the cause of the disease in 47 of these patients. The majority of these organisms were resistant to most, and in seven cases to all, of the antituberculous drugs. Ten patients responded poorly to treatment and 14 patients (30%) died, 8 of these from uncontrollable pulmonary infection with the atypical organisms. It is suggested that a recent, simplified classification of mycobacteria proposed by Runyon be adopted."} {"id": "PMID:1260603", "title": "Evaluation of stroke disability.", "content": "The disabilities resulting from a stroke are not well understood from the epidemiologic or functional point of view. The stroke may impair mental status, perception, sensation, communication and motor ability; the total resulting disability is related to the extent of impairment in each of these areas. A complete evaluation in all these areas has to be done to determine the degree of disability before any rehabilitation program is planned. A comprehensive approach to evaluating stroke disability is presented that includes correlating the degree of impairment in each of the above-mentioned areas with the overall functional ability of the patient.", "contents": "Evaluation of stroke disability. The disabilities resulting from a stroke are not well understood from the epidemiologic or functional point of view. The stroke may impair mental status, perception, sensation, communication and motor ability; the total resulting disability is related to the extent of impairment in each of these areas. A complete evaluation in all these areas has to be done to determine the degree of disability before any rehabilitation program is planned. A comprehensive approach to evaluating stroke disability is presented that includes correlating the degree of impairment in each of the above-mentioned areas with the overall functional ability of the patient."} {"id": "PMID:1260604", "title": "Control of lithium tremor with propranolol.", "content": "Lithium tremor is an irregular, nonrhythmic tremor of the distal extremities, variable in both intensity and frequency. It is clinically differentiated from essential tremor and tremors due to anxiety and neuroleptics. The pathophysiologic mechanisms are hypothesized to be of perpheral origin. Five patients were successfully treated with propranolol. In general, the dosage of propranolol must be individually adjusted and is usually from 30 to 40 mg daily in divided doses. This blocker of beta-adrenergic receptors remains effective with long-term administration and increases in dosage are not required.", "contents": "Control of lithium tremor with propranolol. Lithium tremor is an irregular, nonrhythmic tremor of the distal extremities, variable in both intensity and frequency. It is clinically differentiated from essential tremor and tremors due to anxiety and neuroleptics. The pathophysiologic mechanisms are hypothesized to be of perpheral origin. Five patients were successfully treated with propranolol. In general, the dosage of propranolol must be individually adjusted and is usually from 30 to 40 mg daily in divided doses. This blocker of beta-adrenergic receptors remains effective with long-term administration and increases in dosage are not required."} {"id": "PMID:1260614", "title": "The Canadian Home Fitness Test as a predictor for aerobic capacity.", "content": "The purpose of this study was to determine if maximum oxygen consumption (Vo(2) max) could be predicted from independent variables measured during the administration of the Canadian Home Fitness Test. Fifty-nine subjects between the ages of 15 and 74 years underwent the fitness test and a progressive exercise treadmill test for the direct determination of volitional Vo(2) max. The results indicated that Vo(2) max could be adequately predicted by the following regression equation: Vo(2) max (ml/kg.min) = 42.5 + 16.6(Vo(2)) - 0.12(W) - 0.12(H) - 0.24(A), where Vo(2) is the average oxygen cost of the last completed exercise stage (in l/min), W is the body weight (in kg), H is the postexercise heart rate (in beats/min) and A is the age (in years).", "contents": "The Canadian Home Fitness Test as a predictor for aerobic capacity. The purpose of this study was to determine if maximum oxygen consumption (Vo(2) max) could be predicted from independent variables measured during the administration of the Canadian Home Fitness Test. Fifty-nine subjects between the ages of 15 and 74 years underwent the fitness test and a progressive exercise treadmill test for the direct determination of volitional Vo(2) max. The results indicated that Vo(2) max could be adequately predicted by the following regression equation: Vo(2) max (ml/kg.min) = 42.5 + 16.6(Vo(2)) - 0.12(W) - 0.12(H) - 0.24(A), where Vo(2) is the average oxygen cost of the last completed exercise stage (in l/min), W is the body weight (in kg), H is the postexercise heart rate (in beats/min) and A is the age (in years)."} {"id": "PMID:1260615", "title": "Management of \"psychosomatic\" problems in clinical practice.", "content": "Skilled interviewing and investigation are essential in the diagnosis and treatment of \"psychosomatic\" illness, the term \"psychosomatic\" being used in its more colloquial sense to refer to illness characterized by somatic symptoms and related psychopathologic disorders but without organic disease.Treatment of these patients is difficult. They respond best to a psychologically oriented physician who is able and willing to take final responsibility for both physical and psychological care. The hazards of ignoring the psychosocial dimension in patient management are emphasized. Although the family physician generally is the most appropriate therapist, there may be a role for a \"liaison physician\", a specially trained consultant who is thoroughly familiar with both physical and psychological processes and their interaction.", "contents": "Management of \"psychosomatic\" problems in clinical practice. Skilled interviewing and investigation are essential in the diagnosis and treatment of \"psychosomatic\" illness, the term \"psychosomatic\" being used in its more colloquial sense to refer to illness characterized by somatic symptoms and related psychopathologic disorders but without organic disease.Treatment of these patients is difficult. They respond best to a psychologically oriented physician who is able and willing to take final responsibility for both physical and psychological care. The hazards of ignoring the psychosocial dimension in patient management are emphasized. Although the family physician generally is the most appropriate therapist, there may be a role for a \"liaison physician\", a specially trained consultant who is thoroughly familiar with both physical and psychological processes and their interaction."} {"id": "PMID:1260616", "title": "Locked wards in Canadian mental hospitals: the return to custodialism.", "content": "In 1975 a survey of the open- and locked-ward practice of 38 of the 44 Canadian public mental hospitals showed that more than one third of the wards are locked 24 hours a day. This survey is the only one known to have been conducted in the last 16 years and the first to have obtained data from all 10 provinces. Hospitals with fewer than 300 beds have a significantly smaller proportion of locked wards than those with more than 600 beds.The custodial, antitherapeutic environment was the most frequently cited disadvantage of the locked ward, and facilitation of the therapeutic milieu was the most commonly cited advantage of the open ward. The most commonly cited problem of the open ward was the inability to protect the community from the dangerous, violent patient. The most frequently cited factor required to open the wards was a higher nursing staff:patient ratio, but it is suggested that this is an erroneous opinion. What is required is the organization and involvement of the patients in meaningful activities throughout the day, hospitals with fewer beds, and better relations with the community to foster public tolerance.National organizations concerned with mental hospital practice have no data on the open- and locked-ward practice in this country. There are pressures, channelled through the political and judicial systems, to lock the wards, and the Law Reform Commission of Canada has recently recommended transferring mentally ill prisoners to mental hospitals.", "contents": "Locked wards in Canadian mental hospitals: the return to custodialism. In 1975 a survey of the open- and locked-ward practice of 38 of the 44 Canadian public mental hospitals showed that more than one third of the wards are locked 24 hours a day. This survey is the only one known to have been conducted in the last 16 years and the first to have obtained data from all 10 provinces. Hospitals with fewer than 300 beds have a significantly smaller proportion of locked wards than those with more than 600 beds.The custodial, antitherapeutic environment was the most frequently cited disadvantage of the locked ward, and facilitation of the therapeutic milieu was the most commonly cited advantage of the open ward. The most commonly cited problem of the open ward was the inability to protect the community from the dangerous, violent patient. The most frequently cited factor required to open the wards was a higher nursing staff:patient ratio, but it is suggested that this is an erroneous opinion. What is required is the organization and involvement of the patients in meaningful activities throughout the day, hospitals with fewer beds, and better relations with the community to foster public tolerance.National organizations concerned with mental hospital practice have no data on the open- and locked-ward practice in this country. There are pressures, channelled through the political and judicial systems, to lock the wards, and the Law Reform Commission of Canada has recently recommended transferring mentally ill prisoners to mental hospitals."} {"id": "PMID:1260617", "title": "Exercise London: a disaster exercise involving numerous casualties.", "content": "A large-scale disaster exercise was conducted to assess how one large community would handle such a situation - particularly, how it would deal with 150 casualties. The planning, undertaken by a subcommittee composed of representatives of all resource groups in the city, took more than a year. The deficiencies of the disaster plan detected during the exercise, which included a lack of trained personnel and various problems of communication, are now being corrected.", "contents": "Exercise London: a disaster exercise involving numerous casualties. A large-scale disaster exercise was conducted to assess how one large community would handle such a situation - particularly, how it would deal with 150 casualties. The planning, undertaken by a subcommittee composed of representatives of all resource groups in the city, took more than a year. The deficiencies of the disaster plan detected during the exercise, which included a lack of trained personnel and various problems of communication, are now being corrected."} {"id": "PMID:1260651", "title": "Chemotherapy of malignant diffuse mesothelioma.", "content": "The clinicopathologic features of six pleural and one peritoneal mesothelioma were analyzed. Six patients were treated with either adriamycin or a multiple drug regimen consisting of cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil (COMF). Of those who received COMF, one obtained a complete response lasting 19 months and two had partial responses lasting 3 and 7 months. Adriamycin was administered to five patients. Two obtained a complete response lasting 19 and 7 months. Three had partial responses lasting 2, 6, and 9 months. Grading of response was often difficult requiring serial review of chest x-rays. Survival from diagnosis ranged from 2 to 39 months, with a median of 9 months. We conclude that adriamycin or COMF treatment may offer worthwhile remissions in mesothelioma and that malignant diffuse mesothelioma is more responsive to chemotherapy than previously realized.", "contents": "Chemotherapy of malignant diffuse mesothelioma. The clinicopathologic features of six pleural and one peritoneal mesothelioma were analyzed. Six patients were treated with either adriamycin or a multiple drug regimen consisting of cyclophosphamide, vincristine, methotrexate, and 5-fluorouracil (COMF). Of those who received COMF, one obtained a complete response lasting 19 months and two had partial responses lasting 3 and 7 months. Adriamycin was administered to five patients. Two obtained a complete response lasting 19 and 7 months. Three had partial responses lasting 2, 6, and 9 months. Grading of response was often difficult requiring serial review of chest x-rays. Survival from diagnosis ranged from 2 to 39 months, with a median of 9 months. We conclude that adriamycin or COMF treatment may offer worthwhile remissions in mesothelioma and that malignant diffuse mesothelioma is more responsive to chemotherapy than previously realized."} {"id": "PMID:1260652", "title": "Combination chemotherapy with cyclophosphamide, vincristine, and prednisone in advanced non-Hodgkin's lymphomas.", "content": "From July 1971 to July 1974, 58 patients with advanced non-Hodgkin's lymphomas were treated with cyclophosphamide, vincristine, prednisone (CVP) at Stanford Medical Center. Utilizing the histopathologic criteria of Rappaport el al., response to CVP was found to be significantly better in the nodular (96.6%) and the diffuse lymphocytic (100%) histologies as compared to the diffuse nonlymphocytic lymphomas (47.6%). A pathologically documented complete remission was obtained in 33.9% of patients and all but two remain disease free for periods of 2-28 months. Concurrent bleomycin was administered to 17 patients during CVP therapy and no improvement in response or median survival was noted. Prior radiation therapy delivered to 21 patients did not adversely affect their response to CVP or their survival. Splenectomy in 17 patients prior to CVP did not improve hematologic tolerance to chemotherapy except in those patients with prior radiation therapy, and there was no improvement in response to CVP or survival. CVP is effective in achieving complete remissions and extended disease-free survivals in advanced non-Hodgkin's lymphomas; both a nodular architecture and a diffuse lymphocytic histology are positive determinants for response to chemotherapy and improved median survival.", "contents": "Combination chemotherapy with cyclophosphamide, vincristine, and prednisone in advanced non-Hodgkin's lymphomas. From July 1971 to July 1974, 58 patients with advanced non-Hodgkin's lymphomas were treated with cyclophosphamide, vincristine, prednisone (CVP) at Stanford Medical Center. Utilizing the histopathologic criteria of Rappaport el al., response to CVP was found to be significantly better in the nodular (96.6%) and the diffuse lymphocytic (100%) histologies as compared to the diffuse nonlymphocytic lymphomas (47.6%). A pathologically documented complete remission was obtained in 33.9% of patients and all but two remain disease free for periods of 2-28 months. Concurrent bleomycin was administered to 17 patients during CVP therapy and no improvement in response or median survival was noted. Prior radiation therapy delivered to 21 patients did not adversely affect their response to CVP or their survival. Splenectomy in 17 patients prior to CVP did not improve hematologic tolerance to chemotherapy except in those patients with prior radiation therapy, and there was no improvement in response to CVP or survival. CVP is effective in achieving complete remissions and extended disease-free survivals in advanced non-Hodgkin's lymphomas; both a nodular architecture and a diffuse lymphocytic histology are positive determinants for response to chemotherapy and improved median survival."} {"id": "PMID:1260653", "title": "Diminished bone marrow responsiveness to erythropoietin in myelophthisic anemia.", "content": "The purpose of this study was to examine a mechanism which might explain the diminished erythropoiesis that occurs when tumor cells invade the bone marrow (myelophthisic anemia). To this end we compared 21 patients with neoplastic bone marrow invasion with seven normal subjects. When erythropoietin was added to bone marrow cell cultures from the normal subjects, the baseline rate of heme synthesis for a specific number of marrow erythroid cells increased 65%. In contrast, in patients with greater than 60% of the marrow replaced by tumor, the marrow cell culture response to erythropoietin was 14% above baseline. A significant inverse correlation was noted between the degree of marrow infiltration with tumor and the stimulation of heme synthesis with erythropoietin. It is proposed that marrow invasion with tumor may result in decreased marrow response to erythropoietin, and hence, diminished red cell production.", "contents": "Diminished bone marrow responsiveness to erythropoietin in myelophthisic anemia. The purpose of this study was to examine a mechanism which might explain the diminished erythropoiesis that occurs when tumor cells invade the bone marrow (myelophthisic anemia). To this end we compared 21 patients with neoplastic bone marrow invasion with seven normal subjects. When erythropoietin was added to bone marrow cell cultures from the normal subjects, the baseline rate of heme synthesis for a specific number of marrow erythroid cells increased 65%. In contrast, in patients with greater than 60% of the marrow replaced by tumor, the marrow cell culture response to erythropoietin was 14% above baseline. A significant inverse correlation was noted between the degree of marrow infiltration with tumor and the stimulation of heme synthesis with erythropoietin. It is proposed that marrow invasion with tumor may result in decreased marrow response to erythropoietin, and hence, diminished red cell production."} {"id": "PMID:1260654", "title": "Ultrastructure of the basal cell adenoma of parotid gland.", "content": "Electron microscopic examination of two classical examples of so-called basal cell adenoma of parotid gland disclosed four distinct cellular types: the squamous epithelial cells with tonofilaments and prominent desmosomes predominantly located at the central portion of neoplastic mass; the basally located secretory cells with numerous secretory granules; the occasional intermediate cells with scanty cytoplasmic microfilaments; and the peripherally situated attenuated myoepithelial cells. The neoplastic clusters are surrounded by highly replicated basal laminae with microfibrils in their interstices. This information about its component cells suggests that basal cell adenoma arises from the secretory duct, in particular the intercalated duct, of the parotid gland. The term basal cell adenoma appears appropriate for its designation. It is interesting that the secretory cells and the multilayered basal laminae illustrated in the present study are reportedly seen in adenoid cystic carcinoma of the salivary gland; this finding would suggest a common cellular origin for these two neoplasms.", "contents": "Ultrastructure of the basal cell adenoma of parotid gland. Electron microscopic examination of two classical examples of so-called basal cell adenoma of parotid gland disclosed four distinct cellular types: the squamous epithelial cells with tonofilaments and prominent desmosomes predominantly located at the central portion of neoplastic mass; the basally located secretory cells with numerous secretory granules; the occasional intermediate cells with scanty cytoplasmic microfilaments; and the peripherally situated attenuated myoepithelial cells. The neoplastic clusters are surrounded by highly replicated basal laminae with microfibrils in their interstices. This information about its component cells suggests that basal cell adenoma arises from the secretory duct, in particular the intercalated duct, of the parotid gland. The term basal cell adenoma appears appropriate for its designation. It is interesting that the secretory cells and the multilayered basal laminae illustrated in the present study are reportedly seen in adenoid cystic carcinoma of the salivary gland; this finding would suggest a common cellular origin for these two neoplasms."} {"id": "PMID:1260655", "title": "Adult neuroblastoma. Electron microscopic observations in nine cases.", "content": "Nine patients, whose ages ranged from 18 to 72, had small round cell neoplasms which were found on electron microscopy to have the ultrastructural features of neuroblastoma. The primary tumor was retroperitoneal in one patient. In another, liver and bone metastases were present and the primary site was not determined. The tumor presented in a peripheral location in the remaining seven patients (leg in two, buttock in one, head and neck in four), and all seven tumors metastasized to regional lymph nodes. One tumor that arose in the nasal cavity displayed olfactory differentiation. Two tumors recurred locally following excision. Although two patients have died from disseminated disease, the prognosis nevertheless appears more favorable than in childhood neuroblastoma. Adequate local excision of a peripheral lesion with close follow-up are indicated.", "contents": "Adult neuroblastoma. Electron microscopic observations in nine cases. Nine patients, whose ages ranged from 18 to 72, had small round cell neoplasms which were found on electron microscopy to have the ultrastructural features of neuroblastoma. The primary tumor was retroperitoneal in one patient. In another, liver and bone metastases were present and the primary site was not determined. The tumor presented in a peripheral location in the remaining seven patients (leg in two, buttock in one, head and neck in four), and all seven tumors metastasized to regional lymph nodes. One tumor that arose in the nasal cavity displayed olfactory differentiation. Two tumors recurred locally following excision. Although two patients have died from disseminated disease, the prognosis nevertheless appears more favorable than in childhood neuroblastoma. Adequate local excision of a peripheral lesion with close follow-up are indicated."} {"id": "PMID:1260656", "title": "Chondrosarcoma with dedifferentiated foci. A comparative and ultrastructural study.", "content": "The light and electron microscopic features of a well-differentiated chondrosarcoma with dedifferentiated foci (CDF) are compared with those of a poorly differentiated chondrosarcoma with spindle cell elements. The differentiation of this lesion from mesenchymal chondrosarcoma and from primitive multipotential primary sarcoma of bone is discussed. Ultrastructurally, the cells of the cartilaginous region of the CDF resembled those of the poorly differentiated chondrosarcoma and of the cartilaginous zones of an extraskeletal mesenchymal chondrosarcoma reported by Fu and Kay, and were characterised by an abundance of dilated endoplasmic reticulum and a scalloped and microvillous cell membrane. The stroma was devoid of mature crossbanded collagen fibers. The dedifferentiated portion was composed of mesenchymal-type cells surrounded by a relatively sparse matrix containing scanty mature collagen fibers; these cells resembled those in the cellular regions of the two previously documented mesenchymal chondrosarcomas but differed from the cartilaginous type cells in the cellular regions of the poorly differentiated chondrosarcoma.", "contents": "Chondrosarcoma with dedifferentiated foci. A comparative and ultrastructural study. The light and electron microscopic features of a well-differentiated chondrosarcoma with dedifferentiated foci (CDF) are compared with those of a poorly differentiated chondrosarcoma with spindle cell elements. The differentiation of this lesion from mesenchymal chondrosarcoma and from primitive multipotential primary sarcoma of bone is discussed. Ultrastructurally, the cells of the cartilaginous region of the CDF resembled those of the poorly differentiated chondrosarcoma and of the cartilaginous zones of an extraskeletal mesenchymal chondrosarcoma reported by Fu and Kay, and were characterised by an abundance of dilated endoplasmic reticulum and a scalloped and microvillous cell membrane. The stroma was devoid of mature crossbanded collagen fibers. The dedifferentiated portion was composed of mesenchymal-type cells surrounded by a relatively sparse matrix containing scanty mature collagen fibers; these cells resembled those in the cellular regions of the two previously documented mesenchymal chondrosarcomas but differed from the cartilaginous type cells in the cellular regions of the poorly differentiated chondrosarcoma."} {"id": "PMID:1260657", "title": "A clinicopathologic and prognostic study of epithelial tumors of the renal pelvis.", "content": "The aim of the present investigation was to assess the prognosis of epithelial pelvic tumors and evaluate from multivariate analysis the influence of different morphologic and clinical factors on the prognosis. The basic data are derived from the Swedish national series of patients with epithelial renal pelvic tumors diagnosed by histologic examination during 1962-63. Ninety-four of the 102 patients studied had a urothelial pelvic tumor and eight had an epidermoid carcinoma. The corrected 5-year survival rate was 51% in the curatively operated series, 60% among the males and 33% among the females. Infiltration depth was found to be of significant importance for the 5-year survival and thus a strong predictor for prognosis. Furthermore, each tumor grade and tumor structure exerts some influence on the prognosis independent of the infiltration depth. Nine patients had verified, and 16 patients had suspected phenacetin abuse and/or renal papillary necrosis. The survival rate was low and the relative frequency of females was high in this group of patients. These data may indicate a poorer prognosis in patients with phenacetin abuse, and may explain the sex difference in 5-year survival. Thirty-eight per cent of the patients with urothelial tumors of the renal pelvis had a synchronous or asynchronous tumor elsewhere in the urinary tract. The high frequency of local recurrence as well as the high frequency of infiltrating tumors and multiple tumors indicate the necessity for a more extensive operation such as perifascial nephrectomy with total ureterectomy including a cuff of the bladder.", "contents": "A clinicopathologic and prognostic study of epithelial tumors of the renal pelvis. The aim of the present investigation was to assess the prognosis of epithelial pelvic tumors and evaluate from multivariate analysis the influence of different morphologic and clinical factors on the prognosis. The basic data are derived from the Swedish national series of patients with epithelial renal pelvic tumors diagnosed by histologic examination during 1962-63. Ninety-four of the 102 patients studied had a urothelial pelvic tumor and eight had an epidermoid carcinoma. The corrected 5-year survival rate was 51% in the curatively operated series, 60% among the males and 33% among the females. Infiltration depth was found to be of significant importance for the 5-year survival and thus a strong predictor for prognosis. Furthermore, each tumor grade and tumor structure exerts some influence on the prognosis independent of the infiltration depth. Nine patients had verified, and 16 patients had suspected phenacetin abuse and/or renal papillary necrosis. The survival rate was low and the relative frequency of females was high in this group of patients. These data may indicate a poorer prognosis in patients with phenacetin abuse, and may explain the sex difference in 5-year survival. Thirty-eight per cent of the patients with urothelial tumors of the renal pelvis had a synchronous or asynchronous tumor elsewhere in the urinary tract. The high frequency of local recurrence as well as the high frequency of infiltrating tumors and multiple tumors indicate the necessity for a more extensive operation such as perifascial nephrectomy with total ureterectomy including a cuff of the bladder."} {"id": "PMID:1260658", "title": "Relationship between serum selenium levels and patients with carcinoma.", "content": "Serum selenium levels were determined by neutron activation analysis on 110 patients with carcinoma. An attempt was made to correlate the wide range in the serum concentrations of the trace element with the parameters employed in this study. An association was noted between the serum selenium levels and patient survival time, incidence of multiple primary malignancies, rate of recurrence of the primary lesion and the extent of local and disseminated involvement.", "contents": "Relationship between serum selenium levels and patients with carcinoma. Serum selenium levels were determined by neutron activation analysis on 110 patients with carcinoma. An attempt was made to correlate the wide range in the serum concentrations of the trace element with the parameters employed in this study. An association was noted between the serum selenium levels and patient survival time, incidence of multiple primary malignancies, rate of recurrence of the primary lesion and the extent of local and disseminated involvement."} {"id": "PMID:1260659", "title": "Relationships of morphology to clinical presentation in ten cases of early squamous cell carcinoma of the lung.", "content": "The morphologic changes in 10 patients who were found to have squamous cell carcinoma of the lung before they became evident on chest x ray are discussed. It is suggested that these cases have a long preclinical course as invasive carcinomas that ranges from a microscopic focus of microinvasion (possibly originating from in situ carcinoma in submucosal gland epithelium) to a large concentric carcinoma which may have metastasized to regional lymph nodes. Although the duration of the in situ phase of squamous cell carcinoma of the bronchus in not known, it was evident that the expanse of in situ carcinoma frequently far exceeded that of the invasive carcinoma, and usually extended proximal to the invasive lesion. It is important that the extent of the in situ lesion is determined preoperatively. Finally, multifocal in situ (or invasive) carcinoma was found in at least two of the cases, either synchronously or metachronously.", "contents": "Relationships of morphology to clinical presentation in ten cases of early squamous cell carcinoma of the lung. The morphologic changes in 10 patients who were found to have squamous cell carcinoma of the lung before they became evident on chest x ray are discussed. It is suggested that these cases have a long preclinical course as invasive carcinomas that ranges from a microscopic focus of microinvasion (possibly originating from in situ carcinoma in submucosal gland epithelium) to a large concentric carcinoma which may have metastasized to regional lymph nodes. Although the duration of the in situ phase of squamous cell carcinoma of the bronchus in not known, it was evident that the expanse of in situ carcinoma frequently far exceeded that of the invasive carcinoma, and usually extended proximal to the invasive lesion. It is important that the extent of the in situ lesion is determined preoperatively. Finally, multifocal in situ (or invasive) carcinoma was found in at least two of the cases, either synchronously or metachronously."} {"id": "PMID:1260660", "title": "CEA family syndrome. Abnormal carcinoembryonic antigen (CEA) levels in asymptomatic retinoblastoma family members.", "content": "Plasma carcinoembryonic antigen (CEA) levels were studied in all available members of 17 families in which a presumed sporadic retinoblastoma had occurred. In 9 of the 17 families, close relatives of the patient had elevated CEA levels in the absence of demonstrable disease; this we have termed the \"CEA family syndrome.\" In two families (Nos. 8 and 17) one or both parents and all of the siblings had elevated CEA levels. To our knowledge, this is the first report of abnormal CEA levels in unaffected family members of patients with nonadenocarcinoma-type malignancies. As follow-up studies of such families become available, detection of the \"CEA family syndrome\" may prove to be a useful means of locating individuals with inherited premalignant or malignant conditions and may provide a stimulus for additional clinical examination of asymptomatic individuals considered at risk for developing malignancies.", "contents": "CEA family syndrome. Abnormal carcinoembryonic antigen (CEA) levels in asymptomatic retinoblastoma family members. Plasma carcinoembryonic antigen (CEA) levels were studied in all available members of 17 families in which a presumed sporadic retinoblastoma had occurred. In 9 of the 17 families, close relatives of the patient had elevated CEA levels in the absence of demonstrable disease; this we have termed the \"CEA family syndrome.\" In two families (Nos. 8 and 17) one or both parents and all of the siblings had elevated CEA levels. To our knowledge, this is the first report of abnormal CEA levels in unaffected family members of patients with nonadenocarcinoma-type malignancies. As follow-up studies of such families become available, detection of the \"CEA family syndrome\" may prove to be a useful means of locating individuals with inherited premalignant or malignant conditions and may provide a stimulus for additional clinical examination of asymptomatic individuals considered at risk for developing malignancies."} {"id": "PMID:1260661", "title": "Histiocytic medullary reticulosis with parallel increases in serum acid phosphatase and disease activity.", "content": "Two months after presenting with autoimmune hemolytic anemia, a 57-year-old man developed increased serum acid phosphatase activity. Subsequently, abnormal histiocytes were found in the bone marrow and blood, and 8 months after the onset of his illness lymph node biopsy led to the diagnosis of histiocytic medullary reticulosis. At that time the level of serum acid phosphatase activity was more than 60 times the upper limit of normal and then paralleled the activity of his disease during temporary responses to chemotherapy, rising to over 90 times normal at the time of his death 1 year after presentation. No prostatic malignancy was demonstrated by biopsies or at autopsy, and electrophoretic studies of the serum enzyme suggested that it was of extraprostatic origin. It is postulated that the acid phosphate present in the serum at levels heretofore described only in metastatic carcinoma of the prostate may have arisen from the abnormal histiocytes.", "contents": "Histiocytic medullary reticulosis with parallel increases in serum acid phosphatase and disease activity. Two months after presenting with autoimmune hemolytic anemia, a 57-year-old man developed increased serum acid phosphatase activity. Subsequently, abnormal histiocytes were found in the bone marrow and blood, and 8 months after the onset of his illness lymph node biopsy led to the diagnosis of histiocytic medullary reticulosis. At that time the level of serum acid phosphatase activity was more than 60 times the upper limit of normal and then paralleled the activity of his disease during temporary responses to chemotherapy, rising to over 90 times normal at the time of his death 1 year after presentation. No prostatic malignancy was demonstrated by biopsies or at autopsy, and electrophoretic studies of the serum enzyme suggested that it was of extraprostatic origin. It is postulated that the acid phosphate present in the serum at levels heretofore described only in metastatic carcinoma of the prostate may have arisen from the abnormal histiocytes."} {"id": "PMID:1260662", "title": "Bone marrow scanning with 52iron (52Fe). Regeneration and extension of marrow after ablative doses of radiotherapy.", "content": "Extensively irradiated patients were studied from 0 to 73 months after irradiation by 52Fe bone marrow scanning. Marrow regeneration was observed in most patients after intervals of 12 months or longer. The degree of recovery was not dose-related and the marrow ablative dose was not defined with doses of 4000-5000 rads. Degree of recovery depended more upon the antomic region and/or sequence of fields treated; the last field treated invariably showed poorer regeneration when recovery was uneven. Active erythropoisis expanded into distal inactive erthropoietic sites from 3-12 months after irradiation and then decreased thereafter. Blood count cytopenias were almost always restricted to the first year after irradiation.", "contents": "Bone marrow scanning with 52iron (52Fe). Regeneration and extension of marrow after ablative doses of radiotherapy. Extensively irradiated patients were studied from 0 to 73 months after irradiation by 52Fe bone marrow scanning. Marrow regeneration was observed in most patients after intervals of 12 months or longer. The degree of recovery was not dose-related and the marrow ablative dose was not defined with doses of 4000-5000 rads. Degree of recovery depended more upon the antomic region and/or sequence of fields treated; the last field treated invariably showed poorer regeneration when recovery was uneven. Active erythropoisis expanded into distal inactive erthropoietic sites from 3-12 months after irradiation and then decreased thereafter. Blood count cytopenias were almost always restricted to the first year after irradiation."} {"id": "PMID:1260663", "title": "Patterns of extension as a guide to radiation therapy in the management of ovarian neoplasms in children.", "content": "Sixteen cases of childhood malignant ovarian neoplasms of varied histology and stages were reviewed with special reference to the patterns of disease extension within the pelvis and abdomen. All patients had initial surgery elsewhere before referral to Memorial Hospital. Two patients had distant metastases (bone and lung). None of the other 14 girls had disease restricted to the pelvis. The first extension in 11 was to sites within the abdominal cavity as well as to the pelvis and in three to the abdomen without pelvic involvement. Total abdominal irradiation would have been required to encompass all known disease-bearing areas in these 14 girls.", "contents": "Patterns of extension as a guide to radiation therapy in the management of ovarian neoplasms in children. Sixteen cases of childhood malignant ovarian neoplasms of varied histology and stages were reviewed with special reference to the patterns of disease extension within the pelvis and abdomen. All patients had initial surgery elsewhere before referral to Memorial Hospital. Two patients had distant metastases (bone and lung). None of the other 14 girls had disease restricted to the pelvis. The first extension in 11 was to sites within the abdominal cavity as well as to the pelvis and in three to the abdomen without pelvic involvement. Total abdominal irradiation would have been required to encompass all known disease-bearing areas in these 14 girls."} {"id": "PMID:1260664", "title": "Cancer of the nasal cavity.", "content": "The experience with 40 consecutive cases of cancer of the nasal cavity seen over a period of 15 years is presented. Males outnumbered females in a ratio or 5 to 3. Age ranged from 35 to 88 years, and the median age was 67 years. Epidermoid carcinoma accounted for 78% of the cases. Smoking from early age was a noticeable habit among these patients. The median length of smoking history was 51 years. Most lesions were diagnosed in an advanced stage of the disease, 58% of the cases being T3 lesions. Regional lymph nodes metastases were infrequent; only 12% of the patients presented nodes on admission; another 5% developed metastatic nodes during the follow-up period. An overall 5-year survival of 56% was obtained. The survival of cases with T1N0 lesions was 91%. Radiation therapy was the treatment of choice employed in 85% of the cases. A 5-year survival of 50% was obtained in these patients. Irradiation offers an additional means of salvaging recurrences after surgery. The special characteristics of tumors of the nasal cavity merit the evaluation of such lesions separately from tumors of the paranasal sinuses.", "contents": "Cancer of the nasal cavity. The experience with 40 consecutive cases of cancer of the nasal cavity seen over a period of 15 years is presented. Males outnumbered females in a ratio or 5 to 3. Age ranged from 35 to 88 years, and the median age was 67 years. Epidermoid carcinoma accounted for 78% of the cases. Smoking from early age was a noticeable habit among these patients. The median length of smoking history was 51 years. Most lesions were diagnosed in an advanced stage of the disease, 58% of the cases being T3 lesions. Regional lymph nodes metastases were infrequent; only 12% of the patients presented nodes on admission; another 5% developed metastatic nodes during the follow-up period. An overall 5-year survival of 56% was obtained. The survival of cases with T1N0 lesions was 91%. Radiation therapy was the treatment of choice employed in 85% of the cases. A 5-year survival of 50% was obtained in these patients. Irradiation offers an additional means of salvaging recurrences after surgery. The special characteristics of tumors of the nasal cavity merit the evaluation of such lesions separately from tumors of the paranasal sinuses."} {"id": "PMID:1260665", "title": "Nasopharyngeal cancer in Bermuda.", "content": "Six cases of nasopharyngeal carcinoma (NPC) were diagnosed in residents of Bermuda in the 7-year period 1966-1972. While epidemiologic study revealed no history of common environmental exposures, two of the six cases occurred in adult sibs from a family in which a third adult sib developed NPC in 1963. These three cases were from a large, possibly in-bred Portuguese family with origins in the Azores Islands. The remaining four cases were all in black children ages 10-15; two of these were first cousins. These observations suggest the possibility that genetic influence may contribute to the etiology of NPC.", "contents": "Nasopharyngeal cancer in Bermuda. Six cases of nasopharyngeal carcinoma (NPC) were diagnosed in residents of Bermuda in the 7-year period 1966-1972. While epidemiologic study revealed no history of common environmental exposures, two of the six cases occurred in adult sibs from a family in which a third adult sib developed NPC in 1963. These three cases were from a large, possibly in-bred Portuguese family with origins in the Azores Islands. The remaining four cases were all in black children ages 10-15; two of these were first cousins. These observations suggest the possibility that genetic influence may contribute to the etiology of NPC."} {"id": "PMID:1260666", "title": "Malignant mesothelioma of the tunica vaginalis propria testis in a patient with asbestos exposure. A case report.", "content": "A case of malignant mesothelioma arising from the tunica vaginalis propria testis is described. The nature of this tumor is evidenced by in situ malignant change of the mesothelial lining as well as by extensive lymphatic and local tissue invasion. This is the first report of a malignant mesothelioma of the tunica vaginalis associated with asbestos exposure and may be epidemiologically as well as clinically important.", "contents": "Malignant mesothelioma of the tunica vaginalis propria testis in a patient with asbestos exposure. A case report. A case of malignant mesothelioma arising from the tunica vaginalis propria testis is described. The nature of this tumor is evidenced by in situ malignant change of the mesothelial lining as well as by extensive lymphatic and local tissue invasion. This is the first report of a malignant mesothelioma of the tunica vaginalis associated with asbestos exposure and may be epidemiologically as well as clinically important."} {"id": "PMID:1260667", "title": "Spinal cord compression in malignant lymphoma. Treatment and results.", "content": "The natural history, treatment, and results of 73 spinal cord compressions caused by malignant lymphomas are analyzed. It is found that the spinal cord compression caused by malignant lymphomas is generally a late manifestation of the illness, although primary or early involvements are occasionally seen. In our study, reticulum cell sarcoma is the most frequently variety followed by Hodgkin's disease and lymphosarcoma. The dorsal spinal cord is the most frequently involved segment and pain, weakness, and paresthesia are cardinal symptoms. Radiation treatment delivered in the early phase of the compression is commonly successful in reversing the neurologic symptoms and a dose above 2500 rads appears to be optimal for local control of disease. The low incidence of cerivcal cord compression in Hodgkin's disease patients may be related to frequent manifestation and irradiation of the neck nodes in these patients. Early detection of disease in the deep seated areas along the spinal cord and irradiation of these areas may prevent progression of tumor to the epidural space.", "contents": "Spinal cord compression in malignant lymphoma. Treatment and results. The natural history, treatment, and results of 73 spinal cord compressions caused by malignant lymphomas are analyzed. It is found that the spinal cord compression caused by malignant lymphomas is generally a late manifestation of the illness, although primary or early involvements are occasionally seen. In our study, reticulum cell sarcoma is the most frequently variety followed by Hodgkin's disease and lymphosarcoma. The dorsal spinal cord is the most frequently involved segment and pain, weakness, and paresthesia are cardinal symptoms. Radiation treatment delivered in the early phase of the compression is commonly successful in reversing the neurologic symptoms and a dose above 2500 rads appears to be optimal for local control of disease. The low incidence of cerivcal cord compression in Hodgkin's disease patients may be related to frequent manifestation and irradiation of the neck nodes in these patients. Early detection of disease in the deep seated areas along the spinal cord and irradiation of these areas may prevent progression of tumor to the epidural space."} {"id": "PMID:1260668", "title": "Metastatic tumors to the bones of the foot.", "content": "Information on lesions that are metastatic to the bones of the feet is limited. Review of the literature revealed only 17 cases, nine of which were confirmed histologically. Our series involved the clinical records, roentgenograms, and pathologic specimens in eight cases of biopsy-proven metastatic involvement of the bones of the foot. In three additional cases, there was clinical and roentgenographic evidence of metastatic osseous foot lesion but biopsy was not done to provide histiolgic confirmation. Genitourinary malignancies tended to be associated with metastasis to the bones of the feet, the calcaneus being the commonest site of involvement. Although metastatic lesions of the foot are rare, foot pain may be suggestive of an occult carcinoma. Foot pain was the initial presenting complaint in five of our eight cases. The pathogenesis of these distal metastatic lesions remains obscure. Specific problems in management are associated with osseous metastases of the foot.", "contents": "Metastatic tumors to the bones of the foot. Information on lesions that are metastatic to the bones of the feet is limited. Review of the literature revealed only 17 cases, nine of which were confirmed histologically. Our series involved the clinical records, roentgenograms, and pathologic specimens in eight cases of biopsy-proven metastatic involvement of the bones of the foot. In three additional cases, there was clinical and roentgenographic evidence of metastatic osseous foot lesion but biopsy was not done to provide histiolgic confirmation. Genitourinary malignancies tended to be associated with metastasis to the bones of the feet, the calcaneus being the commonest site of involvement. Although metastatic lesions of the foot are rare, foot pain may be suggestive of an occult carcinoma. Foot pain was the initial presenting complaint in five of our eight cases. The pathogenesis of these distal metastatic lesions remains obscure. Specific problems in management are associated with osseous metastases of the foot."} {"id": "PMID:1260669", "title": "Adenocarcinoma of the pancreas in childhood. Report of a case and a review of the English language literature.", "content": "A case of adenocarcinoma of the head of the pancreas in a 13-year-old girl is reported. Some areas simulated an islet cell tumor by light microscopy, but contained numerous eosinophilic granules which were PAS-positive and diastase resistant. Ultrastructurally, the granules were large (960 mum-3000 mum in diameter) and electron-dense, resembling zymogen granules. These granules often showed focal to complete degeneration, occassionally being continuous with a myelin figure. The granules of true islet cell tumors are ultrastructurally distinctive and it is urged, therefore, that all pancreatic neoplasms in children be studied by histochemistry and electron microscopy. Carcinoma of the pancreas in childhood is a rare tumor, often with a rapid clinical course resulting in death. Morphologic separation of cases reported in the English language literature can be made on the basis of acinar differentiation. This feature has been suggested as a peculiarity of childhood pancreatic carcinoma. However, there is a suggestion that this phenomenon occurs in a small percentage of adult tumours as well. More extensive morphologic studies in adult pancreatic cancer may be warranted.", "contents": "Adenocarcinoma of the pancreas in childhood. Report of a case and a review of the English language literature. A case of adenocarcinoma of the head of the pancreas in a 13-year-old girl is reported. Some areas simulated an islet cell tumor by light microscopy, but contained numerous eosinophilic granules which were PAS-positive and diastase resistant. Ultrastructurally, the granules were large (960 mum-3000 mum in diameter) and electron-dense, resembling zymogen granules. These granules often showed focal to complete degeneration, occassionally being continuous with a myelin figure. The granules of true islet cell tumors are ultrastructurally distinctive and it is urged, therefore, that all pancreatic neoplasms in children be studied by histochemistry and electron microscopy. Carcinoma of the pancreas in childhood is a rare tumor, often with a rapid clinical course resulting in death. Morphologic separation of cases reported in the English language literature can be made on the basis of acinar differentiation. This feature has been suggested as a peculiarity of childhood pancreatic carcinoma. However, there is a suggestion that this phenomenon occurs in a small percentage of adult tumours as well. More extensive morphologic studies in adult pancreatic cancer may be warranted."} {"id": "PMID:1260670", "title": "Carcinoma of the pancreas: review of MGH experience from 1963 to 1973. Analysis of surgical failure and implications for radiation therapy.", "content": "A retrospective study was done of all patients who were seen for definitive treatment of adenocarcinoma of the pancreas at the Massachusetts General Hospital from 1963 to 1973. There were a total of 145 patients. Thirty-one patients were treated with radical surgery, with a 16% operative mortality, a 5-year crude survival rate of 15%, and a local recurrence rate of 50%. Sixty-two patients were treated with biopsy alone, with no 5-year survivors. In addition, there were 35 patients who did not have a radical surgical procedure performed only because of the extent of the local disease. It is proposed that postoperative irradiation may reduce the incidence of local failure after radical surgery, and that preoperative radiation therapy or radiation therapy alone would be an appropriate treatment of those patients in whom the local extent of disease is initially too far advanced to perform radical surgery.", "contents": "Carcinoma of the pancreas: review of MGH experience from 1963 to 1973. Analysis of surgical failure and implications for radiation therapy. A retrospective study was done of all patients who were seen for definitive treatment of adenocarcinoma of the pancreas at the Massachusetts General Hospital from 1963 to 1973. There were a total of 145 patients. Thirty-one patients were treated with radical surgery, with a 16% operative mortality, a 5-year crude survival rate of 15%, and a local recurrence rate of 50%. Sixty-two patients were treated with biopsy alone, with no 5-year survivors. In addition, there were 35 patients who did not have a radical surgical procedure performed only because of the extent of the local disease. It is proposed that postoperative irradiation may reduce the incidence of local failure after radical surgery, and that preoperative radiation therapy or radiation therapy alone would be an appropriate treatment of those patients in whom the local extent of disease is initially too far advanced to perform radical surgery."} {"id": "PMID:1260671", "title": "Fulminating parapontine epidermoid carcinoma in a four-year-old boy.", "content": "An unique case of primary intracranial epidermoid carcinoma in a 4-year-old boy is described. Its parapontine localization and malignant features combined to produce a fulminating clinical course simulating an intra-axial mass lesion. The probable origin of the carcinoma from a benign epidermoid cyst is discussed. A review of the world's literature establishes not only the rarity of cyst-derived intracranial epidermoid carcinoma, but also its unprecedented occurrence in a child.", "contents": "Fulminating parapontine epidermoid carcinoma in a four-year-old boy. An unique case of primary intracranial epidermoid carcinoma in a 4-year-old boy is described. Its parapontine localization and malignant features combined to produce a fulminating clinical course simulating an intra-axial mass lesion. The probable origin of the carcinoma from a benign epidermoid cyst is discussed. A review of the world's literature establishes not only the rarity of cyst-derived intracranial epidermoid carcinoma, but also its unprecedented occurrence in a child."} {"id": "PMID:1260672", "title": "Management of malignant testicular tumors in children.", "content": "The result of therapy of 67 cases of children with malignant testicular tumors is presented. The majority of these cases were embryonal carcinoma in which metastases had occurred in the retroperitoneal lymph nodes, lungs, and bones. Long-term survival was obtained in 89% of the cases treated by simple orchiectomy followed by retroperitoneal irradiation. Two cases with metastases benefitted from chemotherapy. The prognosis of embryonal carcinoma of the testis is correlated with the age of the patient and the histologic pattern of the carcinoma; early detection and appropriate treatment are most important for its cure.", "contents": "Management of malignant testicular tumors in children. The result of therapy of 67 cases of children with malignant testicular tumors is presented. The majority of these cases were embryonal carcinoma in which metastases had occurred in the retroperitoneal lymph nodes, lungs, and bones. Long-term survival was obtained in 89% of the cases treated by simple orchiectomy followed by retroperitoneal irradiation. Two cases with metastases benefitted from chemotherapy. The prognosis of embryonal carcinoma of the testis is correlated with the age of the patient and the histologic pattern of the carcinoma; early detection and appropriate treatment are most important for its cure."} {"id": "PMID:1260673", "title": "Pseudosarcoma and carcinosarcoma of the esophagus.", "content": "Two cases of polypoid carcinoma with pseudosarcoma and one of so-called carcinosarcoma of the esophagus are presented. The clinical and morphologic characteristics of these tumors are described and the literature is reviewed. It is postulated that pseudosarcomas and so-called carcinosarcomas belong essentially to the same pathologic entity because of their similar morphologic and biologic aspects. The histogenesis of the sarcoma-like elements of these tumors support the theory of epithelial origin on the basis of the sarcoma-like transformation of squamous cell carcinoma and of the presence of epithelial elements in the \"sarcomatous\" areas.", "contents": "Pseudosarcoma and carcinosarcoma of the esophagus. Two cases of polypoid carcinoma with pseudosarcoma and one of so-called carcinosarcoma of the esophagus are presented. The clinical and morphologic characteristics of these tumors are described and the literature is reviewed. It is postulated that pseudosarcomas and so-called carcinosarcomas belong essentially to the same pathologic entity because of their similar morphologic and biologic aspects. The histogenesis of the sarcoma-like elements of these tumors support the theory of epithelial origin on the basis of the sarcoma-like transformation of squamous cell carcinoma and of the presence of epithelial elements in the \"sarcomatous\" areas."} {"id": "PMID:1260674", "title": "Intramural squamous cell carcinoma of the esophagus.", "content": "A case of squamous cell carcinoma arising from an esophageal intramural squamous epithelial cyst is reported. Review of the literature reveals no previous reports of malignant transformation of esophageal cysts, although there have been reports of approximately 64 cases of benign esophageal cysts, and 35 cases of carcinoma arising in esophageal diverticula. In the present case, there was a history of increasing dysphagia for 2 months. Esophagram demonstrated a 4.5-cm concentric narrowing of the proximal esophagus just below the superior esophageal ring. Esophagoscopies revealed an esophageal stricture with intact mucosa, and bronchoscopy showed the lesion to be producing tracheal deviation. Multiple esophageal biopsies revealed mild mucosal hyperplasia with deep submucosal inflammatory changes suggesting an underlying lesion. Despite lack of histologic proof of malignancy, the patient underwent radiation therapy and bleomycin chemotherapy on the basis of the highly suggestive radiographic findings, but died with bilateral bronchopneumonia 6 months after admission. Autopsy demonstrated a 1.5-cm long intramural esophageal squamous epithelial cyst, from which arose a locally invasive squamous cell carcinoma, without mucosal involvement or metastases. There was no demonstrable evidence of any associated esophageal diverticulum.", "contents": "Intramural squamous cell carcinoma of the esophagus. A case of squamous cell carcinoma arising from an esophageal intramural squamous epithelial cyst is reported. Review of the literature reveals no previous reports of malignant transformation of esophageal cysts, although there have been reports of approximately 64 cases of benign esophageal cysts, and 35 cases of carcinoma arising in esophageal diverticula. In the present case, there was a history of increasing dysphagia for 2 months. Esophagram demonstrated a 4.5-cm concentric narrowing of the proximal esophagus just below the superior esophageal ring. Esophagoscopies revealed an esophageal stricture with intact mucosa, and bronchoscopy showed the lesion to be producing tracheal deviation. Multiple esophageal biopsies revealed mild mucosal hyperplasia with deep submucosal inflammatory changes suggesting an underlying lesion. Despite lack of histologic proof of malignancy, the patient underwent radiation therapy and bleomycin chemotherapy on the basis of the highly suggestive radiographic findings, but died with bilateral bronchopneumonia 6 months after admission. Autopsy demonstrated a 1.5-cm long intramural esophageal squamous epithelial cyst, from which arose a locally invasive squamous cell carcinoma, without mucosal involvement or metastases. There was no demonstrable evidence of any associated esophageal diverticulum."} {"id": "PMID:1260675", "title": "Primitive neuroectodermal tumor (neuroblastoma) arising in sciatic nerve of a child.", "content": "A well-documented case of a primitive neuroectodermal tumor (neuroblastoma) arising in the sciatic nerve of a 6-year old boy is presented. After radical surgical excision of the tumor, followed by chemotherapy, the child remained clinically free of disease for 20 months. Tumor then recurred locally followed by widespread dissemination. He expired 2 years postoperatively. The literature on this type of rare and controversial tumor of peripheral nerves is reviewed. Only a very few reported cases are considered fully acceptable. Interest in this subject, and adequate documentation of future reported cases may lead to a better understanding of this class of malignant tumors.", "contents": "Primitive neuroectodermal tumor (neuroblastoma) arising in sciatic nerve of a child. A well-documented case of a primitive neuroectodermal tumor (neuroblastoma) arising in the sciatic nerve of a 6-year old boy is presented. After radical surgical excision of the tumor, followed by chemotherapy, the child remained clinically free of disease for 20 months. Tumor then recurred locally followed by widespread dissemination. He expired 2 years postoperatively. The literature on this type of rare and controversial tumor of peripheral nerves is reviewed. Only a very few reported cases are considered fully acceptable. Interest in this subject, and adequate documentation of future reported cases may lead to a better understanding of this class of malignant tumors."} {"id": "PMID:1260676", "title": "Olfactory neuroblastoma. A clinical analysis of 17 cases.", "content": "Seventeen patients with olfactory neuroblastoma seen at the Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary from 1941 to 1971 are presented. Data on age, sex, symptoms, physical, and roentgenographic findings, and therapeutic results are evaluated. A system of pretherapy staging is proposed in which for Group A, the tumor is limited to the nasal cavity; in group B, the tumor is localized to the nasal acvity and paranasal sinuses; and in group C, the tumor extends beyond the nasal cavity and paranasal sinuses. Olfactory neuroblastoma is a radioresponsive, and, to a limited extent, radiocurable tumor and varies in aggressiveness. Of 17 patients in this series, 13 or 76% were alive without disease following treatment by surgery, irradiation, and combination of these two methods. Uncontrolled primary lesions with or without metastases accounted for all therapeutic failures. A treatment policy for this disease is presented.", "contents": "Olfactory neuroblastoma. A clinical analysis of 17 cases. Seventeen patients with olfactory neuroblastoma seen at the Massachusetts General Hospital and Massachusetts Eye and Ear Infirmary from 1941 to 1971 are presented. Data on age, sex, symptoms, physical, and roentgenographic findings, and therapeutic results are evaluated. A system of pretherapy staging is proposed in which for Group A, the tumor is limited to the nasal cavity; in group B, the tumor is localized to the nasal acvity and paranasal sinuses; and in group C, the tumor extends beyond the nasal cavity and paranasal sinuses. Olfactory neuroblastoma is a radioresponsive, and, to a limited extent, radiocurable tumor and varies in aggressiveness. Of 17 patients in this series, 13 or 76% were alive without disease following treatment by surgery, irradiation, and combination of these two methods. Uncontrolled primary lesions with or without metastases accounted for all therapeutic failures. A treatment policy for this disease is presented."} {"id": "PMID:1260677", "title": "Malignant oncocytoma of the parotid gland. A light and electron microscopic study.", "content": "A case malignant oncocytoma of the parotid gland occurring in a 91-year-old man is reported. The tumor recurred 10-months and 2 1/2 years after the primary excision. Both primary and recurrent tumors exhibited an infiltrative pattern. The histologic appearance of the original tumor and the recurrent lesion were similar, but there were areas of increased mitotic activity and pleomorphism in the latter. Ultrastructural examination of the recurrent tumor revealed that the cytoplasm was packed with mitochondria. The fine structure was, for the most part, similar to the benign variant reported previously. In the present tumor, however, intercellular spaces were more prominent and a basal lamina was not observed. The malignant oncocytoma occurs both in major and minor salivary glands. The tumor mostly affects the older age group, but the biologic behavior cannot be evaluated fully because of the paucity of cases reported and the lack of follow-up information.", "contents": "Malignant oncocytoma of the parotid gland. A light and electron microscopic study. A case malignant oncocytoma of the parotid gland occurring in a 91-year-old man is reported. The tumor recurred 10-months and 2 1/2 years after the primary excision. Both primary and recurrent tumors exhibited an infiltrative pattern. The histologic appearance of the original tumor and the recurrent lesion were similar, but there were areas of increased mitotic activity and pleomorphism in the latter. Ultrastructural examination of the recurrent tumor revealed that the cytoplasm was packed with mitochondria. The fine structure was, for the most part, similar to the benign variant reported previously. In the present tumor, however, intercellular spaces were more prominent and a basal lamina was not observed. The malignant oncocytoma occurs both in major and minor salivary glands. The tumor mostly affects the older age group, but the biologic behavior cannot be evaluated fully because of the paucity of cases reported and the lack of follow-up information."} {"id": "PMID:1260678", "title": "Basal cell adenoma of the parotid gland. Case report with ultrastructural observations.", "content": "A case of basal cell adenoma of the parotid gland is reported. The tumor was studied by electron microscopy, and fine structural features included numerous desmosomes, large secretory granules, and replication of the basal lamina. Myoepithelial cells were not observed. The observations support the view that the tumor is monomorphic and that it arises from serous cells of the acini or intercalated ducts. The tumor may be the benign homolog of the adenoid cystic carcinoma.", "contents": "Basal cell adenoma of the parotid gland. Case report with ultrastructural observations. A case of basal cell adenoma of the parotid gland is reported. The tumor was studied by electron microscopy, and fine structural features included numerous desmosomes, large secretory granules, and replication of the basal lamina. Myoepithelial cells were not observed. The observations support the view that the tumor is monomorphic and that it arises from serous cells of the acini or intercalated ducts. The tumor may be the benign homolog of the adenoid cystic carcinoma."} {"id": "PMID:1260679", "title": "Involved field radiation therapy for early stage Hodgkin's disease in children: preliminary results.", "content": "Twenty Stage I and II children with Hodgkin's disease were treated with involved field radiation therapy. Twelve patients were Stage I. The histologic types were:nodular sclerosis(seven cases), mixed cellularity (two) and lymphocyte predominant (three). There were eight Stage II patients (six nodular sclerosis and two of mixed cellularity). One Stage I and 4 Stage II patients had class B disease. Involved field irradiation was used in these children after staging laparotomy showed no disease below the diaphragm. Eight of the 20 patients relapsed, five in lymph nodes adjacent to the primary site, two in areas across the diaphragm; the other had both local and distant extension. The median time to relapse after completion of radiation therapy for Stage I and II were 15 and 5 months, respectively. Two of the eight children with recurrent disease are dead. The other six were retreated and are alive and free of disease for periods ranging from 24 to 68 months after original treatment (median, 36 months). Two of the six survivors in this group received irradiation to the site of the recurrent disease only, one was given total nodal irradiation, and three had chemotherapy. The other 12 patients are in continuous first remission. They have been followed for a median time of 26 months. The actuarial relapse-free survival and survival rates at 3 years are 57 and 89%, respectively.", "contents": "Involved field radiation therapy for early stage Hodgkin's disease in children: preliminary results. Twenty Stage I and II children with Hodgkin's disease were treated with involved field radiation therapy. Twelve patients were Stage I. The histologic types were:nodular sclerosis(seven cases), mixed cellularity (two) and lymphocyte predominant (three). There were eight Stage II patients (six nodular sclerosis and two of mixed cellularity). One Stage I and 4 Stage II patients had class B disease. Involved field irradiation was used in these children after staging laparotomy showed no disease below the diaphragm. Eight of the 20 patients relapsed, five in lymph nodes adjacent to the primary site, two in areas across the diaphragm; the other had both local and distant extension. The median time to relapse after completion of radiation therapy for Stage I and II were 15 and 5 months, respectively. Two of the eight children with recurrent disease are dead. The other six were retreated and are alive and free of disease for periods ranging from 24 to 68 months after original treatment (median, 36 months). Two of the six survivors in this group received irradiation to the site of the recurrent disease only, one was given total nodal irradiation, and three had chemotherapy. The other 12 patients are in continuous first remission. They have been followed for a median time of 26 months. The actuarial relapse-free survival and survival rates at 3 years are 57 and 89%, respectively."} {"id": "PMID:1260680", "title": "Treatment of Bowen's disease with topical dinitrochlorobenzene and 5-fluorouracil.", "content": "\"Bowen's disease\" is a clinical and histologic diagnosis describing the lesions (single or multiple) of cutaneous in situ squamous cell carcinoma. The case of a 54-year-old man with 60 such intra-epidermal carcinomas, and a history of arsenic ingestion, is presented. The patient was sensitized to dinitrochlorobenzene (DNCB), and his lesions were treated with a topical DNCB preparation. All lesions disappeared completely (demonstrated by biopsy of several sites) except for a large (12 X 7 cm) tumor on the flank which partially resolved. Total regression of this lesion was achieved by adding topical 5-fluorouracil (5-FU) therapy. This case demonstrates that the inflammatory reaction induced by DNCB (as evidenced by erythema and by a dense inflammatory cell infiltrate in biopsied areas of treated lesions) can lead to regression of extensive in situ epidermoid carcinoma, and that combined therapy with DNCB and 5-FU can be more effective than DNCB alone. Both agents in appropriate concentrations led to selective destruction of neoplastic tissue with no effect on adjacent normal skin. No systemic toxicity was observed.", "contents": "Treatment of Bowen's disease with topical dinitrochlorobenzene and 5-fluorouracil. \"Bowen's disease\" is a clinical and histologic diagnosis describing the lesions (single or multiple) of cutaneous in situ squamous cell carcinoma. The case of a 54-year-old man with 60 such intra-epidermal carcinomas, and a history of arsenic ingestion, is presented. The patient was sensitized to dinitrochlorobenzene (DNCB), and his lesions were treated with a topical DNCB preparation. All lesions disappeared completely (demonstrated by biopsy of several sites) except for a large (12 X 7 cm) tumor on the flank which partially resolved. Total regression of this lesion was achieved by adding topical 5-fluorouracil (5-FU) therapy. This case demonstrates that the inflammatory reaction induced by DNCB (as evidenced by erythema and by a dense inflammatory cell infiltrate in biopsied areas of treated lesions) can lead to regression of extensive in situ epidermoid carcinoma, and that combined therapy with DNCB and 5-FU can be more effective than DNCB alone. Both agents in appropriate concentrations led to selective destruction of neoplastic tissue with no effect on adjacent normal skin. No systemic toxicity was observed."} {"id": "PMID:1260681", "title": "Ultrasonic enhancement of nitrogen mustard cytotoxicity in mouse leukemia.", "content": "Mouse leukemia L1210 cells were exposed to continuous wave 2 MHz, 10 W/cm(2) ultrasound for 10 minutes while suspended in nitrogen mustard solution in vitro. Mice subsequently inoculated with these cells had longer survival times than control animals that received cells exposed to the drug but not ultrasound. Without the drug, ultrasound did not alter survival time. Tracer studies revealed increased cellular accumulation of drug under the influence of ultrasound.", "contents": "Ultrasonic enhancement of nitrogen mustard cytotoxicity in mouse leukemia. Mouse leukemia L1210 cells were exposed to continuous wave 2 MHz, 10 W/cm(2) ultrasound for 10 minutes while suspended in nitrogen mustard solution in vitro. Mice subsequently inoculated with these cells had longer survival times than control animals that received cells exposed to the drug but not ultrasound. Without the drug, ultrasound did not alter survival time. Tracer studies revealed increased cellular accumulation of drug under the influence of ultrasound."} {"id": "PMID:1260682", "title": "A study of survival in patients with stomach cancer treated by a combination of preoperative intra-arterial infusion therapy and surgery.", "content": "Since 1968, there have been 62 patients with stomach cancer seen in the First Department of Surgery of Chiba University. Treatment consisted of preoperative intra-arterial chemotherapy and surgery. The chemotherapy entailed continuous infusion for 15 to 20 hours. The survival rates were analyzed with particular emphasis on the degree of serosal invasion of the stomach. The overall survivals at the end of 3 years were 54.2% for the treated patients, and 37.1% for the controls: and at the end of 5 years, 33.3% of the treated patients were living as compared to 29.7% of the control patients. In patients without serosal invasion, the survival rates were higher for those treated than for the controls for the first 2 years. At the end of 3 years, the 39 patients treated for serosal invasion had a survival rate of 46.8% vs. 29% in the controls: and at 5 years, 32.2% of the treated patients vs. 23.7% in the controls. The survival rates for the treated patients with cancerous infiltration of other organs were about the same as those for the corresponding control patients.", "contents": "A study of survival in patients with stomach cancer treated by a combination of preoperative intra-arterial infusion therapy and surgery. Since 1968, there have been 62 patients with stomach cancer seen in the First Department of Surgery of Chiba University. Treatment consisted of preoperative intra-arterial chemotherapy and surgery. The chemotherapy entailed continuous infusion for 15 to 20 hours. The survival rates were analyzed with particular emphasis on the degree of serosal invasion of the stomach. The overall survivals at the end of 3 years were 54.2% for the treated patients, and 37.1% for the controls: and at the end of 5 years, 33.3% of the treated patients were living as compared to 29.7% of the control patients. In patients without serosal invasion, the survival rates were higher for those treated than for the controls for the first 2 years. At the end of 3 years, the 39 patients treated for serosal invasion had a survival rate of 46.8% vs. 29% in the controls: and at 5 years, 32.2% of the treated patients vs. 23.7% in the controls. The survival rates for the treated patients with cancerous infiltration of other organs were about the same as those for the corresponding control patients."} {"id": "PMID:1260683", "title": "Survival of patients with lung cancer treated with vincristine and actinomycin D: An unsuccessful trial.", "content": "Twenty-five patients with lung cancer were treated with actinomycin-D and vincristine (V-D) with only one objective response (IMD). The survival of these patients was compared retrospectively to a group of 49 consecutive patients treated with radiotherapy only during the same time period. Median survival times for the V-D group and radiotherapy controls were 6.5 and 7.5 months, respectively. It is concluded that V-D did not increase survival in patients with lung cancer and should be dropped from the chemotherapeutic armamentarium in lung cancer.", "contents": "Survival of patients with lung cancer treated with vincristine and actinomycin D: An unsuccessful trial. Twenty-five patients with lung cancer were treated with actinomycin-D and vincristine (V-D) with only one objective response (IMD). The survival of these patients was compared retrospectively to a group of 49 consecutive patients treated with radiotherapy only during the same time period. Median survival times for the V-D group and radiotherapy controls were 6.5 and 7.5 months, respectively. It is concluded that V-D did not increase survival in patients with lung cancer and should be dropped from the chemotherapeutic armamentarium in lung cancer."} {"id": "PMID:1260684", "title": "Ameloblastic sarcoma: pathogenesis and treatment with chemotherapy.", "content": "A recurrent tumor in a young male demonstrates the progression of an ameloblastic fibroma to an ameloblastic sarcoma. Chemotherapy with Actinomycin D, Vincristine, and Cytoxan produced a complete response without evidence of recurrence 4 years after initiation of chemotherapy. The patient developed an aggressive malignant melanoma 1 year after all chemotherapy was discontinued.", "contents": "Ameloblastic sarcoma: pathogenesis and treatment with chemotherapy. A recurrent tumor in a young male demonstrates the progression of an ameloblastic fibroma to an ameloblastic sarcoma. Chemotherapy with Actinomycin D, Vincristine, and Cytoxan produced a complete response without evidence of recurrence 4 years after initiation of chemotherapy. The patient developed an aggressive malignant melanoma 1 year after all chemotherapy was discontinued."} {"id": "PMID:1260685", "title": "A correlation of DNCB-induced delayed cutaneous hypersensitivity reactions and the course of disease in patients with recurrent breast cancer.", "content": "Delayed cutaneous hypersensitivity reactions to DNCB were performed before therapy in 84 patients with recurrent breast cancer. Following sensitization, a 100 microgram challenge dose was graded as a strong, weak, or negative reaction. Thirty six patients were rechallenged greater than or equal to 6 months with 109 microgram of DNCB. Patients with a strong delayed cutaneous hypersensitivity reaction to DNCB were characteried by: a significantly higher probability of surviving at 52 and 78 weeks, a longer median length of survival (strong 78 weeks, weak 43 weeks, and negative 35 weeks), and a greater probability of responding to therapy (strong 52%, weak 29%, and negative 23%). It is suggested that patients with histologic grade III tumors with a dense lymphocyte infiltrate had more frequent strong delayed cutaneous hypersensitivity reactions to DNCB than those with few lymphocytes. The correlation of DNCB skin testing with a good prognosis in this group of patients with breast cancer suggests a protective role by the immunologic defense mechanisms and warrants its further evaluation and use in the development of new therapeutic modalities.", "contents": "A correlation of DNCB-induced delayed cutaneous hypersensitivity reactions and the course of disease in patients with recurrent breast cancer. Delayed cutaneous hypersensitivity reactions to DNCB were performed before therapy in 84 patients with recurrent breast cancer. Following sensitization, a 100 microgram challenge dose was graded as a strong, weak, or negative reaction. Thirty six patients were rechallenged greater than or equal to 6 months with 109 microgram of DNCB. Patients with a strong delayed cutaneous hypersensitivity reaction to DNCB were characteried by: a significantly higher probability of surviving at 52 and 78 weeks, a longer median length of survival (strong 78 weeks, weak 43 weeks, and negative 35 weeks), and a greater probability of responding to therapy (strong 52%, weak 29%, and negative 23%). It is suggested that patients with histologic grade III tumors with a dense lymphocyte infiltrate had more frequent strong delayed cutaneous hypersensitivity reactions to DNCB than those with few lymphocytes. The correlation of DNCB skin testing with a good prognosis in this group of patients with breast cancer suggests a protective role by the immunologic defense mechanisms and warrants its further evaluation and use in the development of new therapeutic modalities."} {"id": "PMID:1260686", "title": "The role of immune factors in the survival of circulating tumor cells.", "content": "The effects of immune serum on the survival of hematogenously disseminated malignant cells were investigated in six murine tumor systems with varying immunogenicity. Blood containing circulating tumor cells demonstrable by bioassay was obtained from donor mice with disseminated tumor. The cellular fraction was isolated by centrifugation and resuspended in immune serum obtained from donor animals bearing the same tumor (Group 1), in immune serum from mice bearing a differing tumor (Group 2), or in normal nonimmune serum (Group 3). The mixed cellular and serum fractions were intravenously inoculated into normal recipient mice which were subsequently scored for the development of pulmonary tumors. Similar incidence (35-50%) of pulmonary tumor deposits were seen in Groups 2 and 3. A significant enhancement in the incidence of lung tumors was present in the Group 1 animals for all tumor systems studies. It was suggested that the observed enhancement resulted from factors present in isologous immune serum but absent from both normal serum and immune serum obtained from hosts bearing heterologous tumors.", "contents": "The role of immune factors in the survival of circulating tumor cells. The effects of immune serum on the survival of hematogenously disseminated malignant cells were investigated in six murine tumor systems with varying immunogenicity. Blood containing circulating tumor cells demonstrable by bioassay was obtained from donor mice with disseminated tumor. The cellular fraction was isolated by centrifugation and resuspended in immune serum obtained from donor animals bearing the same tumor (Group 1), in immune serum from mice bearing a differing tumor (Group 2), or in normal nonimmune serum (Group 3). The mixed cellular and serum fractions were intravenously inoculated into normal recipient mice which were subsequently scored for the development of pulmonary tumors. Similar incidence (35-50%) of pulmonary tumor deposits were seen in Groups 2 and 3. A significant enhancement in the incidence of lung tumors was present in the Group 1 animals for all tumor systems studies. It was suggested that the observed enhancement resulted from factors present in isologous immune serum but absent from both normal serum and immune serum obtained from hosts bearing heterologous tumors."} {"id": "PMID:1260687", "title": "Split-course radiotherapy of Hodgkin's disease: local tumor control and normal tissue reactions.", "content": "One hundred and thirty-six consecutive patients with Stage I-II Hodgkin's disease treated between 1965 and 1969 received a standard tumor dose of 40000 rads to clinically recognized disease using daily fractions of 200 rads given 4 or 5 times per week. Continuous and split-course irradiation, the latter with a 2-2 1/2 week interuption midway through the treatment, were employed in 82 and 54 patients, respectively. \"Boost\" doses were never given to residual masses at the completion of treatment with either schedule. No loss of therapeutic effectiveness resulted from split-course irradiation, only a single local recurrence having been observed to date. However, patient tolerance with the latter method was substantially better than with continuous irradiation and resulted in fewer subsequent complications. Furthermore, the low incidence of local recurrence fails to support a practice of administering supplementary irradiation to adenopathy which has not completely resolved after a tumor dose of 40000 rads.", "contents": "Split-course radiotherapy of Hodgkin's disease: local tumor control and normal tissue reactions. One hundred and thirty-six consecutive patients with Stage I-II Hodgkin's disease treated between 1965 and 1969 received a standard tumor dose of 40000 rads to clinically recognized disease using daily fractions of 200 rads given 4 or 5 times per week. Continuous and split-course irradiation, the latter with a 2-2 1/2 week interuption midway through the treatment, were employed in 82 and 54 patients, respectively. \"Boost\" doses were never given to residual masses at the completion of treatment with either schedule. No loss of therapeutic effectiveness resulted from split-course irradiation, only a single local recurrence having been observed to date. However, patient tolerance with the latter method was substantially better than with continuous irradiation and resulted in fewer subsequent complications. Furthermore, the low incidence of local recurrence fails to support a practice of administering supplementary irradiation to adenopathy which has not completely resolved after a tumor dose of 40000 rads."} {"id": "PMID:1260688", "title": "Gonadoblastoma: ultrastructural evidence for testicular origin.", "content": "A gonadoblastoma arising in the dysgenetic gonad of a virilized 17-year-old Caucasian with a female phenotype and with a 45,X0/46, X-ring-Y genotype was studied by light microscopic histochemistry, electron microscopy, and ultrastructural histochemistry. The gonadoblastoma was composed of nests of cells containg large germ cells and small \"granulosa-Sertoli-like cells,\" and stromal tissue containing \"Leydig-like cells.\" The germ cells were identical to those found in normal fetal gonads and in germ cell tumors. Charcot-B\u00f6ttcher crystalloids present in the \"granulosa-Sertoli-like cells\" strongly suggest that they are, in fact, Sertoli cells. Multilayered basal laminae located in the periphery of the tumor nests and in \"hyaline bodies\" were identical to those surrounding the seminiferous tubules of the adult testis. The \"Leydig-like cells\" present in the stroma contained occasional dense bodies and crystalloids which characterize the Leydig cells of the fetal testis. Delta 5-3 beta hydroxysteroid dehydrogenase activity was demonstrated in the periphery of lipid droplets and lysosome-like dense bodies of the Leydig cells, and in some Sertoli cells. The findings support the theory that gonadoblastoma arises in a dysgenetic testis rather than in a dysgenetic ovary.", "contents": "Gonadoblastoma: ultrastructural evidence for testicular origin. A gonadoblastoma arising in the dysgenetic gonad of a virilized 17-year-old Caucasian with a female phenotype and with a 45,X0/46, X-ring-Y genotype was studied by light microscopic histochemistry, electron microscopy, and ultrastructural histochemistry. The gonadoblastoma was composed of nests of cells containg large germ cells and small \"granulosa-Sertoli-like cells,\" and stromal tissue containing \"Leydig-like cells.\" The germ cells were identical to those found in normal fetal gonads and in germ cell tumors. Charcot-B\u00f6ttcher crystalloids present in the \"granulosa-Sertoli-like cells\" strongly suggest that they are, in fact, Sertoli cells. Multilayered basal laminae located in the periphery of the tumor nests and in \"hyaline bodies\" were identical to those surrounding the seminiferous tubules of the adult testis. The \"Leydig-like cells\" present in the stroma contained occasional dense bodies and crystalloids which characterize the Leydig cells of the fetal testis. Delta 5-3 beta hydroxysteroid dehydrogenase activity was demonstrated in the periphery of lipid droplets and lysosome-like dense bodies of the Leydig cells, and in some Sertoli cells. The findings support the theory that gonadoblastoma arises in a dysgenetic testis rather than in a dysgenetic ovary."} {"id": "PMID:1260689", "title": "Characterization of an established cell line (SH-3) derived from pleural effusion of patient with breast cancer.", "content": "Spontaneous emergence of fast-growing cells in prolonged culture of pleural effusion cells obtained from a patient with breast cancer has led to the establishment of a cell line designated as SH-3. By morphological criteria, as revealed by light and electron microscopy, SH-3 cells are epithelial and resumble the poorly differentiated cells of a series of established human tumor cell lines. Their karyotype is hypotetraploid and different from that of HeLa cells. Isoenzyme analysis has shown the presence in the cells of a bone-type alkaline phosphatase and of the fast (A) band of G6PD. The line is free of mycoplasma.", "contents": "Characterization of an established cell line (SH-3) derived from pleural effusion of patient with breast cancer. Spontaneous emergence of fast-growing cells in prolonged culture of pleural effusion cells obtained from a patient with breast cancer has led to the establishment of a cell line designated as SH-3. By morphological criteria, as revealed by light and electron microscopy, SH-3 cells are epithelial and resumble the poorly differentiated cells of a series of established human tumor cell lines. Their karyotype is hypotetraploid and different from that of HeLa cells. Isoenzyme analysis has shown the presence in the cells of a bone-type alkaline phosphatase and of the fast (A) band of G6PD. The line is free of mycoplasma."} {"id": "PMID:1260690", "title": "Familial bilateral papillary cystadenoma of the epididymis: report of three cases in siblings.", "content": "This paper describes an unusual, familial bilateral papillary cystadenoma of the epididymis found in three siblings. The histological characteristics of the tumor were: 1) papillary proliferation of clear cells, consisting of both tall columnar and round ovoid cells, in the efferent duct epithelium; and 2) cystic dilatation of the duct with colloidal material. The present cases were unique in two respects: 1) familial bilateral papillary cystadenomas probably associated with Lindau's disease have not been reported previously: and 2) electron microscopic observations suggested that the tumors originated from the efferent duct.", "contents": "Familial bilateral papillary cystadenoma of the epididymis: report of three cases in siblings. This paper describes an unusual, familial bilateral papillary cystadenoma of the epididymis found in three siblings. The histological characteristics of the tumor were: 1) papillary proliferation of clear cells, consisting of both tall columnar and round ovoid cells, in the efferent duct epithelium; and 2) cystic dilatation of the duct with colloidal material. The present cases were unique in two respects: 1) familial bilateral papillary cystadenomas probably associated with Lindau's disease have not been reported previously: and 2) electron microscopic observations suggested that the tumors originated from the efferent duct."} {"id": "PMID:1260691", "title": "Malignant peritoneal mesothelioma in an inguinal hernia sac.", "content": "An instance of malignant peritoneal mesothelioma that appeared to arise from an inguinal hernia sac is reported. This lesion appeared to be different from nodular mesothelial hyperplasia of hernia sacs.", "contents": "Malignant peritoneal mesothelioma in an inguinal hernia sac. An instance of malignant peritoneal mesothelioma that appeared to arise from an inguinal hernia sac is reported. This lesion appeared to be different from nodular mesothelial hyperplasia of hernia sacs."} {"id": "PMID:1260692", "title": "The prediction of lymph node metastases from oral squamous carcinoma.", "content": "In an attempt to predict which cases of oral and oropharyngeal squamous carcinoma are likely to metastasize to regional lymph nodes a series of 898 cases was grouped according to site, size, grade of histological differentiation, and presence or absence of histologically confirmed regional lymph node metastases. The results were analysed by a logistic multiple regression analysis. They showed that the sites may be divided into three clusters, Cluster 1 consists of tumors of lip, floor of mouth, cheek mucosa, hard palate, and gingiva. These are not significantly different as regards metastasis rate. Cluster 2 consists of tumors of the anterior two-thirds of tongue and has a higher tendency to metastasis than those in Cluster 1. Lesions of the posterior third of tongue and oropharynx form Cluster 3 which exhibits the greatest tendency to metastasis. Sizes of primary lesions are clustered in groups of lesions less than 3 cm, those 3 to less than 4 cm, and those 4 cm or larger, in ascending tendency to metastasis. Well-differentiated and moderately differentiated tumors are not significantly different in their tendency to metastasize and may be reduced to a single cluster, whereas poorly differentiated tumors have a markedly higher metastasis rate. Using these clusters it has been possible to predict the logistically transformed probability of metastasis to a high degree of accuracy (R=0.9398). From this we conclude that if for a given tumor we know to which site, size or differentiation cluster it belongs, we can then estimate its probability of metastasising.", "contents": "The prediction of lymph node metastases from oral squamous carcinoma. In an attempt to predict which cases of oral and oropharyngeal squamous carcinoma are likely to metastasize to regional lymph nodes a series of 898 cases was grouped according to site, size, grade of histological differentiation, and presence or absence of histologically confirmed regional lymph node metastases. The results were analysed by a logistic multiple regression analysis. They showed that the sites may be divided into three clusters, Cluster 1 consists of tumors of lip, floor of mouth, cheek mucosa, hard palate, and gingiva. These are not significantly different as regards metastasis rate. Cluster 2 consists of tumors of the anterior two-thirds of tongue and has a higher tendency to metastasis than those in Cluster 1. Lesions of the posterior third of tongue and oropharynx form Cluster 3 which exhibits the greatest tendency to metastasis. Sizes of primary lesions are clustered in groups of lesions less than 3 cm, those 3 to less than 4 cm, and those 4 cm or larger, in ascending tendency to metastasis. Well-differentiated and moderately differentiated tumors are not significantly different in their tendency to metastasize and may be reduced to a single cluster, whereas poorly differentiated tumors have a markedly higher metastasis rate. Using these clusters it has been possible to predict the logistically transformed probability of metastasis to a high degree of accuracy (R=0.9398). From this we conclude that if for a given tumor we know to which site, size or differentiation cluster it belongs, we can then estimate its probability of metastasising."} {"id": "PMID:1260693", "title": "Sarcoma of the prostate.", "content": "The experience at the University of Iowa Hospitals with 12 patients having sarcoma of the prostate is described. Although the total number of patients is small, two distinct groups can be identified. The infants, children, and young adults presenting with this malignancy had a very poor survival regardless of the therapy administered. However, the older men have generally done well, surviving several years following therapy for the relief of lower urinary tract obstruction. The longest surviving patient was treated by transurethral prostectomy followed by transperineal instillation of radioactive gold. A program of combination therapy utilizing surgery, external irradiation, and triple chemotherapy is suggested for use in children and young adults with prostatic sarcoma.", "contents": "Sarcoma of the prostate. The experience at the University of Iowa Hospitals with 12 patients having sarcoma of the prostate is described. Although the total number of patients is small, two distinct groups can be identified. The infants, children, and young adults presenting with this malignancy had a very poor survival regardless of the therapy administered. However, the older men have generally done well, surviving several years following therapy for the relief of lower urinary tract obstruction. The longest surviving patient was treated by transurethral prostectomy followed by transperineal instillation of radioactive gold. A program of combination therapy utilizing surgery, external irradiation, and triple chemotherapy is suggested for use in children and young adults with prostatic sarcoma."} {"id": "PMID:1260694", "title": "The natural history of nodular lymphoma.", "content": "The clinical and histopathologic characteristics of 65 patients with nodular lymphoma seen at the Massachusetts General Hospital between 1962 and 1972 were reviewed. Five years after diagnosis 54% of these patients were alive, but only 18 percent remained free of disease. Younger patients fared much better (64 percent of those below the age of 50 survived 5 years) than the elderly (only 34 percent of those above the age of 50 survived this long), but histologic subtype by the Rappaport classification was not useful in predicting survival in this series. Individuals with localized disease (80% of those in Stages I and II survived 5 years) experienced better survival than those with dissemination (only 45% of those in Stages III and IV lived this long), but the high relapse rate in Stages I and II indicates that few who presented with localized disease are cured. At the time of death, the histologic pattern had become diffuse in 8 of 18 patients but remained nodular in the other 10. Ten patients treated by total nodal irradiation followed the same survival curve as the remainder treated less radically. It is concluded that nodular lymphoma is an indolent but usually fatal entity: though more than half of our patients survived 5 years, few were cured by the treatments employed.", "contents": "The natural history of nodular lymphoma. The clinical and histopathologic characteristics of 65 patients with nodular lymphoma seen at the Massachusetts General Hospital between 1962 and 1972 were reviewed. Five years after diagnosis 54% of these patients were alive, but only 18 percent remained free of disease. Younger patients fared much better (64 percent of those below the age of 50 survived 5 years) than the elderly (only 34 percent of those above the age of 50 survived this long), but histologic subtype by the Rappaport classification was not useful in predicting survival in this series. Individuals with localized disease (80% of those in Stages I and II survived 5 years) experienced better survival than those with dissemination (only 45% of those in Stages III and IV lived this long), but the high relapse rate in Stages I and II indicates that few who presented with localized disease are cured. At the time of death, the histologic pattern had become diffuse in 8 of 18 patients but remained nodular in the other 10. Ten patients treated by total nodal irradiation followed the same survival curve as the remainder treated less radically. It is concluded that nodular lymphoma is an indolent but usually fatal entity: though more than half of our patients survived 5 years, few were cured by the treatments employed."} {"id": "PMID:1260695", "title": "Primary malignant melanoma of the urinary bladder.", "content": "A melanin-synthesizing tumor of the urinary bladder was studied by light and electron microscopy. Careful clinical evaluation did not reveal evidence for a primary melanoma elsewhere in the patient. The clinical presentation, course of the disease, and demonstration of melanocytes in the bladder epithelium and malignant melanocytes comprising the tumor by light and electron microscopy indicated that the neoplasm was a primary malignant melanoma arising in the bladder.", "contents": "Primary malignant melanoma of the urinary bladder. A melanin-synthesizing tumor of the urinary bladder was studied by light and electron microscopy. Careful clinical evaluation did not reveal evidence for a primary melanoma elsewhere in the patient. The clinical presentation, course of the disease, and demonstration of melanocytes in the bladder epithelium and malignant melanocytes comprising the tumor by light and electron microscopy indicated that the neoplasm was a primary malignant melanoma arising in the bladder."} {"id": "PMID:1260696", "title": "Association of renal injury with combined cephalothin-gentamicin therapy among patients severely ill with malignant disease.", "content": "There is a high incidence of primary renal tubule damage among patients with malignant disease who die following recent treatment with combinations of cephalothin and gentamicin. Administration of this combination of antibiotics appears to make the patient appreciably more susceptible to severe renal injury if an additional, often minor, insult to the renal tubules is superimposed. In the present study, significant blood loss or bacterial infection not promptly controlled by the antibiotic combination were two factors that provided this additional insult to many patients; the renal injury in these patients could not be attributed to bleeding or infection alone. The combination of cephalothin plus gentamicin carries the potential of causing renal tubule injury and places the patient severely ill with malignant disease at risk for renal failure from many clinical complications which are commonly associated with their primary illness.", "contents": "Association of renal injury with combined cephalothin-gentamicin therapy among patients severely ill with malignant disease. There is a high incidence of primary renal tubule damage among patients with malignant disease who die following recent treatment with combinations of cephalothin and gentamicin. Administration of this combination of antibiotics appears to make the patient appreciably more susceptible to severe renal injury if an additional, often minor, insult to the renal tubules is superimposed. In the present study, significant blood loss or bacterial infection not promptly controlled by the antibiotic combination were two factors that provided this additional insult to many patients; the renal injury in these patients could not be attributed to bleeding or infection alone. The combination of cephalothin plus gentamicin carries the potential of causing renal tubule injury and places the patient severely ill with malignant disease at risk for renal failure from many clinical complications which are commonly associated with their primary illness."} {"id": "PMID:1260697", "title": "Craniopharyngiomas: a clinical and pathological review.", "content": "Two hundred and forty-five cases of craniopharyngiomas were obtained from the files of the AFIP and reviewed statistically with reference to their gross and microscopic appearance and clinical data. The majority of the tumors were cystic and microscopically, cysts were formed by squamous epithelial maturation, by degeneration of the stellate cells at the centers of adamantinomatous nests, or by degeneration of the stroma. Transitional forms were seen between adamantinomatous and squamous epithelium and keratohyaline granules and keratin were present in some cases. Because of this overlap, differentiation between craniopharyngiomas and suprasellar epidermoid cysts often is not possible. Significantly increased acturial survival rates were associated with absence of calcification in plain skull films in adults, negative CSF examination, and tumor size under 3.0 cm.", "contents": "Craniopharyngiomas: a clinical and pathological review. Two hundred and forty-five cases of craniopharyngiomas were obtained from the files of the AFIP and reviewed statistically with reference to their gross and microscopic appearance and clinical data. The majority of the tumors were cystic and microscopically, cysts were formed by squamous epithelial maturation, by degeneration of the stellate cells at the centers of adamantinomatous nests, or by degeneration of the stroma. Transitional forms were seen between adamantinomatous and squamous epithelium and keratohyaline granules and keratin were present in some cases. Because of this overlap, differentiation between craniopharyngiomas and suprasellar epidermoid cysts often is not possible. Significantly increased acturial survival rates were associated with absence of calcification in plain skull films in adults, negative CSF examination, and tumor size under 3.0 cm."} {"id": "PMID:1260698", "title": "Malignant ovarian tumors in childhood: prognosis in relation to initial therapy.", "content": "Twenty-two children with malignant ovarian tumors (12 malignant teratomas, six endodermal sinus tumors, and four embryonal carcinomas) were studied from 1960 through March 1975. Comparison is made between different modalities of therapy, such as surgery alone or surgery in combination with either radiation or chemotherapy. Because of the poor results obtained with the aforementioned treatment methods, a new approach, consisting of more aggressive initial surgery followed immediately by radiation therapy and an intensive chemotherapeutic regimen called the T2 protocol, was begun in 1971 with encouraging results. To date six of ten patients are alive and free of disease with a median observation period of 22+ months. A new grouping defining the extent of disease is also provided. Of the ten patients on the T2 protocol, only one was a Group I; eight were Group III and one was Group IV at the time treatment was initiated. An analysis of the mode of spread, as well as a discussion of the results obtained with previous modalities of therapy in relation to initial grouping and pathology, constitute the background for the proposed treatment.", "contents": "Malignant ovarian tumors in childhood: prognosis in relation to initial therapy. Twenty-two children with malignant ovarian tumors (12 malignant teratomas, six endodermal sinus tumors, and four embryonal carcinomas) were studied from 1960 through March 1975. Comparison is made between different modalities of therapy, such as surgery alone or surgery in combination with either radiation or chemotherapy. Because of the poor results obtained with the aforementioned treatment methods, a new approach, consisting of more aggressive initial surgery followed immediately by radiation therapy and an intensive chemotherapeutic regimen called the T2 protocol, was begun in 1971 with encouraging results. To date six of ten patients are alive and free of disease with a median observation period of 22+ months. A new grouping defining the extent of disease is also provided. Of the ten patients on the T2 protocol, only one was a Group I; eight were Group III and one was Group IV at the time treatment was initiated. An analysis of the mode of spread, as well as a discussion of the results obtained with previous modalities of therapy in relation to initial grouping and pathology, constitute the background for the proposed treatment."} {"id": "PMID:1260699", "title": "Characteristics of blacks obtaining Papanicolaou smears.", "content": "An understanding of the characteristics of women who do not obtain cervical cytology may shed light on procedures which can be instituted by physicians and public health workers to increase use of screening. Of particular interest are women at high risk of cervical cancer. We interviewed a random sample of about 700 blacks living in central Buffalo census tracts in regard to their past use of pelvic examinations as well as circumstances surrounding such use or non-use. We employed only data on screening which was verified in records. We found that there was decreasing use with increasing age and lack of contact with physicians, clinics, or hospitals. The relationship between increasing use and increasing education was found to be a function of the fact that women with more education are likely to be younger. There was clear evidence that making such examinations part of the contact women have with physicians or hospitals for any purpose, including childbirth, would increase the proportions screened.", "contents": "Characteristics of blacks obtaining Papanicolaou smears. An understanding of the characteristics of women who do not obtain cervical cytology may shed light on procedures which can be instituted by physicians and public health workers to increase use of screening. Of particular interest are women at high risk of cervical cancer. We interviewed a random sample of about 700 blacks living in central Buffalo census tracts in regard to their past use of pelvic examinations as well as circumstances surrounding such use or non-use. We employed only data on screening which was verified in records. We found that there was decreasing use with increasing age and lack of contact with physicians, clinics, or hospitals. The relationship between increasing use and increasing education was found to be a function of the fact that women with more education are likely to be younger. There was clear evidence that making such examinations part of the contact women have with physicians or hospitals for any purpose, including childbirth, would increase the proportions screened."} {"id": "PMID:1260703", "title": "Particle radiation therapy.", "content": "Particle radiation therapy has the potential for immediate and sustained favorable impact on management of the cancer patient by providing better local tumor control. Scientific knowledge and expertise are immediately available to mount effective clinical studies of fast neurons, protons, and helium ions, and to initiate necessary preliminary studies of pimesons and heavy ions. Meaningful studies will require a long-term commitment of support. The amount of support, although substantial, is not disproportionate to the potential benefit or existing support of other cancer research programs.", "contents": "Particle radiation therapy. Particle radiation therapy has the potential for immediate and sustained favorable impact on management of the cancer patient by providing better local tumor control. Scientific knowledge and expertise are immediately available to mount effective clinical studies of fast neurons, protons, and helium ions, and to initiate necessary preliminary studies of pimesons and heavy ions. Meaningful studies will require a long-term commitment of support. The amount of support, although substantial, is not disproportionate to the potential benefit or existing support of other cancer research programs."} {"id": "PMID:1260707", "title": "Anatomical site and size of 222 early asymptomatic oral squamous cell carcinomas: a continuing prospective study of oral cancer. II.", "content": "The site and size of 222 asymptomatic, primarily erythroplastic, cancers of the oral mucosa in 161 patients have been prospectively documented. Of 207 intraoral lesions (excluding 15 of the lip), 201 (97.1%) were found in three locations; floor of the mouth (101), ventral or lateral tongue (36), and soft palate complex (64). Of the 101 in the floor of the mouth, 73 occurred in the anterior portion with 33 involving the papilla at exit of Wharton's Duct (submaxillary gland). Of the cancers 84.2% were 2 cm or less and 41.9% were 1 cm or less. Of the lesions 2 cm or less 70.6% were invasive carcinoma. Minimal size does not preclude invasiveness. In view of the apparent predilection of oral carcinoma for particular sites (where there is no obvious agent), rather than random occurrence, the three aforementioned sites are designated as high risk areas which deserve particular scrutiny in an examination of the oral cavity. It is incumbent upon the clinician to biopsy all asymptomatic, persisten (14 days or more) mucosal aberrations in the high risk areas, especially those with erythroplastic components, regardless of size.", "contents": "Anatomical site and size of 222 early asymptomatic oral squamous cell carcinomas: a continuing prospective study of oral cancer. II. The site and size of 222 asymptomatic, primarily erythroplastic, cancers of the oral mucosa in 161 patients have been prospectively documented. Of 207 intraoral lesions (excluding 15 of the lip), 201 (97.1%) were found in three locations; floor of the mouth (101), ventral or lateral tongue (36), and soft palate complex (64). Of the 101 in the floor of the mouth, 73 occurred in the anterior portion with 33 involving the papilla at exit of Wharton's Duct (submaxillary gland). Of the cancers 84.2% were 2 cm or less and 41.9% were 1 cm or less. Of the lesions 2 cm or less 70.6% were invasive carcinoma. Minimal size does not preclude invasiveness. In view of the apparent predilection of oral carcinoma for particular sites (where there is no obvious agent), rather than random occurrence, the three aforementioned sites are designated as high risk areas which deserve particular scrutiny in an examination of the oral cavity. It is incumbent upon the clinician to biopsy all asymptomatic, persisten (14 days or more) mucosal aberrations in the high risk areas, especially those with erythroplastic components, regardless of size."} {"id": "PMID:1260708", "title": "Antibody response in patients with acute nonlymphocytic leukemia.", "content": "Lymphocytotoxic (LCT) and anti-red blood cell (ABO) antibodies were measured serially in adult patients with acute nonlymphocytic leukemia (ANLL) receiving induction chemotherapy. The antigenic stimulus was provided by multiple platelet transfusions, many of which were ABO incompatible. Comparison of pretherapy titers 4-6 weeks into therapy shows that 50% (19/38) of patients became LCT positive (cytotoxicity against greater than 10% of panel of cells) and 54% (19/35) had increases in ABO titers (greater than 2 tube dilution). A total of 66% of patients had significant rises in at least one antibody. ABO and LCT titers tended to vary in parallel although exceptions were noted. The development of anti) remission rate or duration, 3) type of therapy, 4) number of platelet transfusions, 5) time relationship between the antigenic stimulus and the initiation of cytotoxic therapy, and 6) skin test reactivity. Antibody responders tended to have higher pretreatment lymphocyte counts. The ability to develop a secondary antibody response does not appear to be a major prognostic factor in ANLL.", "contents": "Antibody response in patients with acute nonlymphocytic leukemia. Lymphocytotoxic (LCT) and anti-red blood cell (ABO) antibodies were measured serially in adult patients with acute nonlymphocytic leukemia (ANLL) receiving induction chemotherapy. The antigenic stimulus was provided by multiple platelet transfusions, many of which were ABO incompatible. Comparison of pretherapy titers 4-6 weeks into therapy shows that 50% (19/38) of patients became LCT positive (cytotoxicity against greater than 10% of panel of cells) and 54% (19/35) had increases in ABO titers (greater than 2 tube dilution). A total of 66% of patients had significant rises in at least one antibody. ABO and LCT titers tended to vary in parallel although exceptions were noted. The development of anti) remission rate or duration, 3) type of therapy, 4) number of platelet transfusions, 5) time relationship between the antigenic stimulus and the initiation of cytotoxic therapy, and 6) skin test reactivity. Antibody responders tended to have higher pretreatment lymphocyte counts. The ability to develop a secondary antibody response does not appear to be a major prognostic factor in ANLL."} {"id": "PMID:1260709", "title": "Decreased neutrophil bactericidal activity in acute leukemia of childhood.", "content": "Neutrophil (PMN) bactericidal activity, phagocytosis, and nitroblue tetrazolium (NBT) reduction were evaluated in 18 children with untreated or relapsing acute leukemia and 20 children in hematologic remission. Half of the patients in relapse demonstrated abnormal PMN bactericidal activity, while remission patients had essentially normal PMN bactericidal activity. Phagocytosis of Staphylococcus aureus was normal in relapse and remission subjects. NBT reduction by PMN's of leukemic patients was significantly lower than that of controls, but there was no correlation between decreased NBT-reductase activity and decreased bactericidal power. Six patients in remission had received intensive chemotherapy for more than 4 years, and all demonstrated normal PMN functions. Among relapse patients with abnormal PMN bactericidal activity 63% eventually developed severe bacterial infections. By comparison, 20% of the relapse patients with normal PMN bactericidal activity subsequently developed severe infections. The PMN dysfunction observed in relapse patients suggests that abnormal PMN bactericidal activity may contribute the increased susceptibility to bacterial infections during leukemic relapse.", "contents": "Decreased neutrophil bactericidal activity in acute leukemia of childhood. Neutrophil (PMN) bactericidal activity, phagocytosis, and nitroblue tetrazolium (NBT) reduction were evaluated in 18 children with untreated or relapsing acute leukemia and 20 children in hematologic remission. Half of the patients in relapse demonstrated abnormal PMN bactericidal activity, while remission patients had essentially normal PMN bactericidal activity. Phagocytosis of Staphylococcus aureus was normal in relapse and remission subjects. NBT reduction by PMN's of leukemic patients was significantly lower than that of controls, but there was no correlation between decreased NBT-reductase activity and decreased bactericidal power. Six patients in remission had received intensive chemotherapy for more than 4 years, and all demonstrated normal PMN functions. Among relapse patients with abnormal PMN bactericidal activity 63% eventually developed severe bacterial infections. By comparison, 20% of the relapse patients with normal PMN bactericidal activity subsequently developed severe infections. The PMN dysfunction observed in relapse patients suggests that abnormal PMN bactericidal activity may contribute the increased susceptibility to bacterial infections during leukemic relapse."} {"id": "PMID:1260710", "title": "Immunochemotherapy in human lung cancer using the streptococcal agent OK-432.", "content": "Streptococcal agent OK-432 was administered at maintenance levels with conventional inductive chemotherapeutic agents to stage III and IV lung cancer patients. Survival rates were longer in patients treated with OK-432 than in patients treated without OK-432. An enhancement of lymphocyte blastogenic activity and a delayed PPD skin reaction were found in patients treated by OK-432. A low grade fever was present as a side effect of this agent in some patients. The results suggest that OTK-432 may be useful immunotherapeutic agent in combination with induction chemotherapy in reducing host damage in advanced stages of lung cancer.", "contents": "Immunochemotherapy in human lung cancer using the streptococcal agent OK-432. Streptococcal agent OK-432 was administered at maintenance levels with conventional inductive chemotherapeutic agents to stage III and IV lung cancer patients. Survival rates were longer in patients treated with OK-432 than in patients treated without OK-432. An enhancement of lymphocyte blastogenic activity and a delayed PPD skin reaction were found in patients treated by OK-432. A low grade fever was present as a side effect of this agent in some patients. The results suggest that OTK-432 may be useful immunotherapeutic agent in combination with induction chemotherapy in reducing host damage in advanced stages of lung cancer."} {"id": "PMID:1260711", "title": "CEA levels in head and neck cancer.", "content": "Serum carcinoembryonic antigen (CEA) levels were determined for 439 patients with squamous carcinoma of the head and neck region, 154 healthy smokers, and 122 nonsmokers. Among nonsmokers 95% of the CEA levels did not exceed 5 ng/ml, but among smokers this discriminatory level was 7 ng/ml. Among tumor-bearing patients 36% of the CEA levels exceeded 5 ng/ml but only 17% exceeded 7 ng/ml. Both the incidence and magnitude of CEA elevations correlated with clinical stage of tumor; however, excluding patients with clinically apparent advanced malignancies, the incidence and magnitude of elevations were similar among tumor-bearing patients, tumor-free treated patients, and smokers. Although not predictive of ultimate survival, elevated preoperative CEA levels declined to the range of normals after resection. Similarly, during palliative irradiation for incurable tumors, CEA levels declined with regression of tumor. Irradiation did not nonspecifically elevate CEA levels. The data indicate that in patients with head and neck squamous carcinomas CEA level is not likely to contribute to a determination of prognosis after therapy; however, serial determinations may have adjunctive value in monitoring tumor response.", "contents": "CEA levels in head and neck cancer. Serum carcinoembryonic antigen (CEA) levels were determined for 439 patients with squamous carcinoma of the head and neck region, 154 healthy smokers, and 122 nonsmokers. Among nonsmokers 95% of the CEA levels did not exceed 5 ng/ml, but among smokers this discriminatory level was 7 ng/ml. Among tumor-bearing patients 36% of the CEA levels exceeded 5 ng/ml but only 17% exceeded 7 ng/ml. Both the incidence and magnitude of CEA elevations correlated with clinical stage of tumor; however, excluding patients with clinically apparent advanced malignancies, the incidence and magnitude of elevations were similar among tumor-bearing patients, tumor-free treated patients, and smokers. Although not predictive of ultimate survival, elevated preoperative CEA levels declined to the range of normals after resection. Similarly, during palliative irradiation for incurable tumors, CEA levels declined with regression of tumor. Irradiation did not nonspecifically elevate CEA levels. The data indicate that in patients with head and neck squamous carcinomas CEA level is not likely to contribute to a determination of prognosis after therapy; however, serial determinations may have adjunctive value in monitoring tumor response."} {"id": "PMID:1260712", "title": "Malignant lymphoma of the small intestine in multiple family members: association with an immunologic deficiency.", "content": "Four cases of malignant lymphoma all in male members of a family are described. In three of the affected individuals the primary tumor arose in the small intestine and in the other the site of origin was the retroperitoneum. Immunologic studies were carried out on the two surviving patients and on all other living members of their families. Low levels of immunoglobulins were found in one of the affected boys. During a recurrence of the tumor, the other boy showed temporary partial impairment of cellular immunity as measured by failure to react to delayed hypersensitivity skin tests, although lymphocyte transformation studies were normal. Nine months after treatment was completed his response to skin tests was normal. No immunologic defect was detected in the studies of the non-involved family members. The histologic appearance of the tumors was similar in the tissue sections which were available for review from three of the four patients; the tumor was classified as a malignant lymphoma, diffuse, mixed cell type (lymphocytic and histiocytic).", "contents": "Malignant lymphoma of the small intestine in multiple family members: association with an immunologic deficiency. Four cases of malignant lymphoma all in male members of a family are described. In three of the affected individuals the primary tumor arose in the small intestine and in the other the site of origin was the retroperitoneum. Immunologic studies were carried out on the two surviving patients and on all other living members of their families. Low levels of immunoglobulins were found in one of the affected boys. During a recurrence of the tumor, the other boy showed temporary partial impairment of cellular immunity as measured by failure to react to delayed hypersensitivity skin tests, although lymphocyte transformation studies were normal. Nine months after treatment was completed his response to skin tests was normal. No immunologic defect was detected in the studies of the non-involved family members. The histologic appearance of the tumors was similar in the tissue sections which were available for review from three of the four patients; the tumor was classified as a malignant lymphoma, diffuse, mixed cell type (lymphocytic and histiocytic)."} {"id": "PMID:1260713", "title": "Glassy cell carcinoma of the cervix.", "content": "A clinicopathologic analysis of 13 cases of glassy cell carcinoma of the uterine cervix is presented. The glassy cell carcinoma is considered to be a poorly differentiated mixed adenosquamous carcinoma. Its histologic appearance is distinctive, being characterized by cells with a moderate amount of cytoplasm having a ground glass or finely granular appearance, a distinct cell wall that stains with eosin and PAS, and enlarged nuclei with prominent nucleoli. In the present study this tumor was associated with extrapelvic spread in 6/13 cases at diagnosis. Results were poor with either surgery and/or radiotherapy. Only four of 13 patients survived 5 years. The glassy cell carcinoma appears to be a distinct clinicopathologic entity which warrants a place in the classification of carcinoma of the cervix.", "contents": "Glassy cell carcinoma of the cervix. A clinicopathologic analysis of 13 cases of glassy cell carcinoma of the uterine cervix is presented. The glassy cell carcinoma is considered to be a poorly differentiated mixed adenosquamous carcinoma. Its histologic appearance is distinctive, being characterized by cells with a moderate amount of cytoplasm having a ground glass or finely granular appearance, a distinct cell wall that stains with eosin and PAS, and enlarged nuclei with prominent nucleoli. In the present study this tumor was associated with extrapelvic spread in 6/13 cases at diagnosis. Results were poor with either surgery and/or radiotherapy. Only four of 13 patients survived 5 years. The glassy cell carcinoma appears to be a distinct clinicopathologic entity which warrants a place in the classification of carcinoma of the cervix."} {"id": "PMID:1260714", "title": "Hairy cell leukemia (leukemic reticuloendotheliosis) II. Ultrastructure of the spleen.", "content": "Seven surgically removed spleens from patients with hairy cell leukemia and hypersplenism were examined ultrastructurally. In all spleens the pulp cords were diffusely and compactly infiltrated by hairy cells. Numerous hairy cells were also evident in the often distended sinuses. The hairy projections were readily visible in electron micrographs and tended to interdigitate to form syncytium-like aggregates. Compression of hairy cells within the cords flattened the projections against the cell bodies and may account for the surface alterations reported by scanning electron microscopic studies. Controversy over the cytogenesis of hairy cells has not been resolved by ultrastructural studies. Although all seven patients had hypersplenism, the hairy cells showed no evidence of phagocytic activity. However, active phagocytosis by cordal macrophages was observed and there is a probable absolute increase in their number contributing to the splenomegaly. The dense infiltrate of hairy cells causes marked widening of the cords and retards the passage of formed elements of the blood through the red pulp. Prolonged sojourn of these elements in a metabolically unfavorable environment results in cellular damage, increased exposure to cordal macrophages, and premature destruction with the evolution of a hypersplenic syndrome.", "contents": "Hairy cell leukemia (leukemic reticuloendotheliosis) II. Ultrastructure of the spleen. Seven surgically removed spleens from patients with hairy cell leukemia and hypersplenism were examined ultrastructurally. In all spleens the pulp cords were diffusely and compactly infiltrated by hairy cells. Numerous hairy cells were also evident in the often distended sinuses. The hairy projections were readily visible in electron micrographs and tended to interdigitate to form syncytium-like aggregates. Compression of hairy cells within the cords flattened the projections against the cell bodies and may account for the surface alterations reported by scanning electron microscopic studies. Controversy over the cytogenesis of hairy cells has not been resolved by ultrastructural studies. Although all seven patients had hypersplenism, the hairy cells showed no evidence of phagocytic activity. However, active phagocytosis by cordal macrophages was observed and there is a probable absolute increase in their number contributing to the splenomegaly. The dense infiltrate of hairy cells causes marked widening of the cords and retards the passage of formed elements of the blood through the red pulp. Prolonged sojourn of these elements in a metabolically unfavorable environment results in cellular damage, increased exposure to cordal macrophages, and premature destruction with the evolution of a hypersplenic syndrome."} {"id": "PMID:1260715", "title": "Spindle cell carcinoma: ultrastructural evidence of squamous origin and collagen production by the tumor cells.", "content": "Two cases of spindle cell carcinoma (SCC) of the esophagus and skin, respectively, were studied by transmission electron microscopy. The tumor cells were closely associated with collagen fibrils and had abundant rough endoplasmic reticulum with dilated cisternae. Except for their irregular shape and atypical nuclei they resembled actively synthesizing fibroblasts. In addition to these features, some cells contained numerous tonofibrils and occasional well-developed desmosomes. A gradual transition to typical squamous cells was noted in the skin tumor. These findings suggest that the pseudosarcomatous component of SCC originates from mesenchymal metaplasia of squamous cells and that collagen is produced by these metaplastic cells.", "contents": "Spindle cell carcinoma: ultrastructural evidence of squamous origin and collagen production by the tumor cells. Two cases of spindle cell carcinoma (SCC) of the esophagus and skin, respectively, were studied by transmission electron microscopy. The tumor cells were closely associated with collagen fibrils and had abundant rough endoplasmic reticulum with dilated cisternae. Except for their irregular shape and atypical nuclei they resembled actively synthesizing fibroblasts. In addition to these features, some cells contained numerous tonofibrils and occasional well-developed desmosomes. A gradual transition to typical squamous cells was noted in the skin tumor. These findings suggest that the pseudosarcomatous component of SCC originates from mesenchymal metaplasia of squamous cells and that collagen is produced by these metaplastic cells."} {"id": "PMID:1260716", "title": "Benign vaginal rhabdomyoma: a light and electron microscopic study.", "content": "A benign vaginal rhabdomyoma from a 49-year-old woman was examined by light and electron microscopy. While many of the ultrastructural features conformed to those noted in previously described rhabdomyomas, certain features are described for the first time. These include attachment plaques between cells enclosed within a common basement membrane, cytoplasmic bodies, and peripheral couplings. Finally, the literature is reviewed and the reported cases of rhabdomyoma are divided into adult and fetal types based upon light microscopic criteria.", "contents": "Benign vaginal rhabdomyoma: a light and electron microscopic study. A benign vaginal rhabdomyoma from a 49-year-old woman was examined by light and electron microscopy. While many of the ultrastructural features conformed to those noted in previously described rhabdomyomas, certain features are described for the first time. These include attachment plaques between cells enclosed within a common basement membrane, cytoplasmic bodies, and peripheral couplings. Finally, the literature is reviewed and the reported cases of rhabdomyoma are divided into adult and fetal types based upon light microscopic criteria."} {"id": "PMID:1260717", "title": "Lymphangiomyomatosis: morphogenetic study and ultrastructural confirmation of the histogenesis of the lung lesion.", "content": "A 34-year old woman underwent a surgical intervention as a result of a retroperitoneal tumor. This tumor was excised and the pathological diagnosis was lymphangiomyoma. Two months later she developed a spontaneous right pneumothorax with a chylous pleural effusion. Roentgenograms showed that the lungs had developed a honeycomb pattern. She was treated surgically and at the same time a biopsy was performed. Sixteen months later she deveoped a left pneumothorax which necessitated additional surgery, and a further biopsy was taken. She died of respiratory insufficiency 2 years after the clinical onset of the symptoms. The pathologic material was studied by both electron and light microscopy in serial sections. The electron-microscopic study proved the muscular nature of this condition. The light microscopic study of the serial sections showed that the lung lesion was due to the proliferation of the muscle cells associated with the lymphatics surrounding the acini.", "contents": "Lymphangiomyomatosis: morphogenetic study and ultrastructural confirmation of the histogenesis of the lung lesion. A 34-year old woman underwent a surgical intervention as a result of a retroperitoneal tumor. This tumor was excised and the pathological diagnosis was lymphangiomyoma. Two months later she developed a spontaneous right pneumothorax with a chylous pleural effusion. Roentgenograms showed that the lungs had developed a honeycomb pattern. She was treated surgically and at the same time a biopsy was performed. Sixteen months later she deveoped a left pneumothorax which necessitated additional surgery, and a further biopsy was taken. She died of respiratory insufficiency 2 years after the clinical onset of the symptoms. The pathologic material was studied by both electron and light microscopy in serial sections. The electron-microscopic study proved the muscular nature of this condition. The light microscopic study of the serial sections showed that the lung lesion was due to the proliferation of the muscle cells associated with the lymphatics surrounding the acini."} {"id": "PMID:1260718", "title": "Thyroid cancer: a study of 573 thyroid tumors and 161 autopsy cases observed over a thirty-year period.", "content": "Five hundred and seventy-three thyroid tumors from surgical material and 161 autopsy cases were studied as to incidence, types, and precursor changes using the new WHO-classification. In the surgical material 225 tumors were follicular, 145 papillary, 147 anaplastic, 23 squamous cell, and 10 medullary. Twenty-three sarcomas were found. tthe percentage of follicular carcinoma had decreased, whereas that of papillary carcinoma increased and that of anaplastic carcinoma remained constant. In over 50% of anaplastic carcinomas neoplastic follicular structures have been identified. As a rule the more sections are prepared, the more papillary carcinomas and the less sarcomas are diagnosed. Thyroid tumors leading to death were found in 0.33% of 53,134 consecutive autopsies. Anaplastic (52.3%) and follicular (33.5%) carcinoma were most frequently encountered. Metastases of follicular and anaplastic carcinoma were most often found in the lung, pleura, and bones, whereas lymph nodes of the neck, lung, and bones were predominantly involved in cases of the papillary type. Therapy of thyroid carcinoma is total thyroidectomy. The transition of follicular carcinoma to the anaplastic type has to be avoided whenever possible.", "contents": "Thyroid cancer: a study of 573 thyroid tumors and 161 autopsy cases observed over a thirty-year period. Five hundred and seventy-three thyroid tumors from surgical material and 161 autopsy cases were studied as to incidence, types, and precursor changes using the new WHO-classification. In the surgical material 225 tumors were follicular, 145 papillary, 147 anaplastic, 23 squamous cell, and 10 medullary. Twenty-three sarcomas were found. tthe percentage of follicular carcinoma had decreased, whereas that of papillary carcinoma increased and that of anaplastic carcinoma remained constant. In over 50% of anaplastic carcinomas neoplastic follicular structures have been identified. As a rule the more sections are prepared, the more papillary carcinomas and the less sarcomas are diagnosed. Thyroid tumors leading to death were found in 0.33% of 53,134 consecutive autopsies. Anaplastic (52.3%) and follicular (33.5%) carcinoma were most frequently encountered. Metastases of follicular and anaplastic carcinoma were most often found in the lung, pleura, and bones, whereas lymph nodes of the neck, lung, and bones were predominantly involved in cases of the papillary type. Therapy of thyroid carcinoma is total thyroidectomy. The transition of follicular carcinoma to the anaplastic type has to be avoided whenever possible."} {"id": "PMID:1260719", "title": "Solitary intraparenchymal pulmonary plasmacytoma associated with production of an M-protein: report of a case.", "content": "A case of a 40-year old man who underwent surgical extirpation of a solitary intraparenchymal pulmonary plasmacytoma is reported. To our knowledge, this is the first reported case associated with the production of an M-protien. The production of protein fell dramatically following removal of the tumor.", "contents": "Solitary intraparenchymal pulmonary plasmacytoma associated with production of an M-protein: report of a case. A case of a 40-year old man who underwent surgical extirpation of a solitary intraparenchymal pulmonary plasmacytoma is reported. To our knowledge, this is the first reported case associated with the production of an M-protien. The production of protein fell dramatically following removal of the tumor."} {"id": "PMID:1260720", "title": "Female adnexal tumor of probable Wolffian origin: evidence of a low grade malignancy.", "content": "A broad ligament tumor with the histologic features of a female adnexal tumor of probable Wolffian origin, as described by Kariminejad and Scully, is reported. Although previous cases were thought to be benign, in the present case, hepatic metastasis occurred 6 years after resection of the primary. Cytologic features by light microscopy were more anaplastic than in the original cases. Ultrastructural findings were not specific for any normal adult or fetal mesonephric tissue previously studied by electron microscopy.", "contents": "Female adnexal tumor of probable Wolffian origin: evidence of a low grade malignancy. A broad ligament tumor with the histologic features of a female adnexal tumor of probable Wolffian origin, as described by Kariminejad and Scully, is reported. Although previous cases were thought to be benign, in the present case, hepatic metastasis occurred 6 years after resection of the primary. Cytologic features by light microscopy were more anaplastic than in the original cases. Ultrastructural findings were not specific for any normal adult or fetal mesonephric tissue previously studied by electron microscopy."} {"id": "PMID:1260721", "title": "Benign clear cell tumor of lung with necrosis.", "content": "A case of benign clear cell tumor (\"sugar tumor\") of the lund with extensive necrosis is reported. Electron microscopic study established the diagnosis by virtue of the characteristic cytoplasmic membrane-bound glycogen. Ultrastructural study may be necessary in cases containing necrosis to differentiate this lesion decisively from metastatic renal cell carcinoma.", "contents": "Benign clear cell tumor of lung with necrosis. A case of benign clear cell tumor (\"sugar tumor\") of the lund with extensive necrosis is reported. Electron microscopic study established the diagnosis by virtue of the characteristic cytoplasmic membrane-bound glycogen. Ultrastructural study may be necessary in cases containing necrosis to differentiate this lesion decisively from metastatic renal cell carcinoma."} {"id": "PMID:1260722", "title": "Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases.", "content": "Fifty-eight immature ovarian teratomas were studied. Neoplams with other germ cell elements (endodermal sinus tumor, choriocarcinoma, and dysgerminoma) were excluded so that the clinical and pathologic features of \"pure\" immature teratomas could be defined and correlated with the prognosis. The primary tumors and their metastatic growths were graded from 0 to 3. Forty were stage I; nine, stage II; and nine, stage III. The size and stage of teratomas were related to survival, but it was the grade of the primary tumor that best determined the likelihood of extraovarian spread, and it was the grade of the metastases that related best to the subsequent course. Actuarial survival was 63% at 5 years and also at 10 years. Regardless of the grade of the primary tumor, only one of six with grade 0 metastases progressed, and that neoplasms may not have been adequately sampled. Two of five neoplasms having grade 1 metastases did not progress, and two of six patients with grade 2 metastatic growths were living after relatively long intervals. All seven patients with grade 3 metastases died with tumor, none surviving more than 2.1 years. Survival of patients with grade 1, 2, and 3 neoplasms was 81, 60, and 30% respectively. The importance of adequate sampling of primary tumor and metastases for estimating prognosis and determining therapy is stressed.", "contents": "Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases. Fifty-eight immature ovarian teratomas were studied. Neoplams with other germ cell elements (endodermal sinus tumor, choriocarcinoma, and dysgerminoma) were excluded so that the clinical and pathologic features of \"pure\" immature teratomas could be defined and correlated with the prognosis. The primary tumors and their metastatic growths were graded from 0 to 3. Forty were stage I; nine, stage II; and nine, stage III. The size and stage of teratomas were related to survival, but it was the grade of the primary tumor that best determined the likelihood of extraovarian spread, and it was the grade of the metastases that related best to the subsequent course. Actuarial survival was 63% at 5 years and also at 10 years. Regardless of the grade of the primary tumor, only one of six with grade 0 metastases progressed, and that neoplasms may not have been adequately sampled. Two of five neoplasms having grade 1 metastases did not progress, and two of six patients with grade 2 metastatic growths were living after relatively long intervals. All seven patients with grade 3 metastases died with tumor, none surviving more than 2.1 years. Survival of patients with grade 1, 2, and 3 neoplasms was 81, 60, and 30% respectively. The importance of adequate sampling of primary tumor and metastases for estimating prognosis and determining therapy is stressed."} {"id": "PMID:1260723", "title": "Melanin as a component of cerebral gliomas: the melanotic cerebral ependymoma.", "content": "Even though melanin is found in certain central nervous system neurons and leptomeningeal melanocytes, gliomas rarely possess melanin. A few rare lethal melanotic medulloblastomas found typically in the cerebellar vermis of children have been described, but neuroglial cells have not been observed to contain this pigment. Since glial elements and the melanotic pigmented layer of the retina are derived from the same ciliated epithelium of the embryonic neural tube, recognition of melanin in a cerebral glioma was predictable. Indeed, melanin was observed in a cystic cerebral ependymal glioma from a 30-year-old woman, supporting the potential of glial cells to produce melanin.", "contents": "Melanin as a component of cerebral gliomas: the melanotic cerebral ependymoma. Even though melanin is found in certain central nervous system neurons and leptomeningeal melanocytes, gliomas rarely possess melanin. A few rare lethal melanotic medulloblastomas found typically in the cerebellar vermis of children have been described, but neuroglial cells have not been observed to contain this pigment. Since glial elements and the melanotic pigmented layer of the retina are derived from the same ciliated epithelium of the embryonic neural tube, recognition of melanin in a cerebral glioma was predictable. Indeed, melanin was observed in a cystic cerebral ependymal glioma from a 30-year-old woman, supporting the potential of glial cells to produce melanin."} {"id": "PMID:1260724", "title": "Improved survival in hodgkin's disease.", "content": "All patients below the age of 66 whose Hodgkin's disease was treated at the Massachusetts General Hospital between July 1, 1965 and June 30, 1973 were analyzed. The patients were divided into an early group seen before November 1, 1968 and a later group seen after that date. Survival and survival without recurrence were calculated by the actuarial method of Berkson and Gage, and compared with figures obtained from a historical series seen at this institution between 1948 and 1964. In the most recent period (1969-1973), 87% of patients with all stages of Hodgkin's disease were alive five years after diagnosis, a remarkable improvement over the 65% survival of the 1965-1968 group and the 34% survival of the historical series. The excellent survival of the recent group was a result of improved management of patients with advanced disease (Stages III and IV), most plausibly attributed to better appreciation of the extent of disease by surgical staging and to the shift from total nodal irradiation to combination chemotherapy for initial treatment of these patients. Recurrence after irradiation was extremely uncommon in patients in Stage IA and IIA (lymphangiogram-negative, asymptomatic) subjected to aging laparotomy, while similarly staged and irradiated patients in Stages IB and IIB (lymphangiogram-negative, symptomatic) did much less well. Except for the surgically staged patients in Stages IA and IIA, the continuing high relapse rate indicates that five-year survival, even when relapse-free, is not synonymous with cure, and emphasizes the need for caution in predicting the ultimate cure rate with current therapy.", "contents": "Improved survival in hodgkin's disease. All patients below the age of 66 whose Hodgkin's disease was treated at the Massachusetts General Hospital between July 1, 1965 and June 30, 1973 were analyzed. The patients were divided into an early group seen before November 1, 1968 and a later group seen after that date. Survival and survival without recurrence were calculated by the actuarial method of Berkson and Gage, and compared with figures obtained from a historical series seen at this institution between 1948 and 1964. In the most recent period (1969-1973), 87% of patients with all stages of Hodgkin's disease were alive five years after diagnosis, a remarkable improvement over the 65% survival of the 1965-1968 group and the 34% survival of the historical series. The excellent survival of the recent group was a result of improved management of patients with advanced disease (Stages III and IV), most plausibly attributed to better appreciation of the extent of disease by surgical staging and to the shift from total nodal irradiation to combination chemotherapy for initial treatment of these patients. Recurrence after irradiation was extremely uncommon in patients in Stage IA and IIA (lymphangiogram-negative, asymptomatic) subjected to aging laparotomy, while similarly staged and irradiated patients in Stages IB and IIB (lymphangiogram-negative, symptomatic) did much less well. Except for the surgically staged patients in Stages IA and IIA, the continuing high relapse rate indicates that five-year survival, even when relapse-free, is not synonymous with cure, and emphasizes the need for caution in predicting the ultimate cure rate with current therapy."} {"id": "PMID:1260725", "title": "Pediatric Hodgkin's disease. I. Radiographic evaluation.", "content": "The pretreatment roentgenographic evaluation of 105 consecutive patients less than 16 years of age with Hodgkin's disease was reviewed. The patients were divided into groups aged 1-10 years (37%) and 11-15 years (63%). All patients had chest roentgenograms, of which 36% were abnormal in the younger group and 77% abnormal in the older group. Full-lung tomography was helpful only when the chest film was abnormal or equivocal. Foot lymphography was performed in 103 patients with 20% positive for Hodgkin's disease. Lymphographic-histologic correlation was 98% in the 62 patients undergoing laparotomy. Routine skeletal surveys, as well as examinations of the urinary tract and gastrointestinal tract, were not rewarding.", "contents": "Pediatric Hodgkin's disease. I. Radiographic evaluation. The pretreatment roentgenographic evaluation of 105 consecutive patients less than 16 years of age with Hodgkin's disease was reviewed. The patients were divided into groups aged 1-10 years (37%) and 11-15 years (63%). All patients had chest roentgenograms, of which 36% were abnormal in the younger group and 77% abnormal in the older group. Full-lung tomography was helpful only when the chest film was abnormal or equivocal. Foot lymphography was performed in 103 patients with 20% positive for Hodgkin's disease. Lymphographic-histologic correlation was 98% in the 62 patients undergoing laparotomy. Routine skeletal surveys, as well as examinations of the urinary tract and gastrointestinal tract, were not rewarding."} {"id": "PMID:1260726", "title": "Pediatric hodgkin's disease. II. Results of therapy.", "content": "Between 1962 and 1972, 79 previously untreated children, aged 15 years and under, with biopsy-proven Hodgkin's disease were seen, evaluated, and treated at Standford University Medical Center. The 5-year actuarial survival for all patients was 89%; relapse-free survival was 66%. No relapse was seen following aggressive treatment with irradiation and MOPP chemotherapy. In patients who were pathologically staged, no relapse was seen beyond 2 years. Patients with mixed cellularity subtype fared surprisingly well as compared to those with the nodular sclerosing subtype. An analysis of the types of treatment administered and complications of therapy suggests that the major difference between children and adults with Hodgkin's disease is the potential for long-term sequelae resulting from aggressive treatment. In an attempt to maximize the quality of survival, a proposal is made for low-dose radiation and planned MOPP chemotherapy.", "contents": "Pediatric hodgkin's disease. II. Results of therapy. Between 1962 and 1972, 79 previously untreated children, aged 15 years and under, with biopsy-proven Hodgkin's disease were seen, evaluated, and treated at Standford University Medical Center. The 5-year actuarial survival for all patients was 89%; relapse-free survival was 66%. No relapse was seen following aggressive treatment with irradiation and MOPP chemotherapy. In patients who were pathologically staged, no relapse was seen beyond 2 years. Patients with mixed cellularity subtype fared surprisingly well as compared to those with the nodular sclerosing subtype. An analysis of the types of treatment administered and complications of therapy suggests that the major difference between children and adults with Hodgkin's disease is the potential for long-term sequelae resulting from aggressive treatment. In an attempt to maximize the quality of survival, a proposal is made for low-dose radiation and planned MOPP chemotherapy."} {"id": "PMID:1260727", "title": "Malignant melanoma of the gallbladder: report of three cases and review of the literature.", "content": "Three cases of primary melanoma of the gallbladder are described to add to the five reported in the literature. As an organ of endodermal origin, the gallbladder appears to share the melanoblastic potentiality possessed by similarly derived organs, and hence, the development of a melanoma within the gallbladder is not unexpected. Presence of melanocytes within the gallbladder mucosa is absolute proof that the tumor is primary. Whether these cells originate from the neural crest and migrate to the gallbladder, or result from local differentiation from preexisting cells remains to be answered.", "contents": "Malignant melanoma of the gallbladder: report of three cases and review of the literature. Three cases of primary melanoma of the gallbladder are described to add to the five reported in the literature. As an organ of endodermal origin, the gallbladder appears to share the melanoblastic potentiality possessed by similarly derived organs, and hence, the development of a melanoma within the gallbladder is not unexpected. Presence of melanocytes within the gallbladder mucosa is absolute proof that the tumor is primary. Whether these cells originate from the neural crest and migrate to the gallbladder, or result from local differentiation from preexisting cells remains to be answered."} {"id": "PMID:1260728", "title": "Prostatic carcinoma: some morphological features affecting prognosis.", "content": "Morphologic features in 146 cases of prostatic carcinoma were correlated with 5-year survival. Simple probability tests showed a significant prognostic difference of the presence or absence of cell borders, lymphocytic infiltration, pleomorphism of nuclei, and McNeal's typing. Further statistical analysis, with a probability test which was adjusted for the distribution of these factors, showed that only the presence or absence of cell borders and lymphocytic infiltration affected prognosis. It is very important for the pathologist reporting on prostate carcinoma to include mention of these factors in his report because of their prognostic importance. In particular it should be noted that if the tumor has indistinct cell borders and there is no lymphocytic infiltration, then it is likely to have a very poor prognosis.", "contents": "Prostatic carcinoma: some morphological features affecting prognosis. Morphologic features in 146 cases of prostatic carcinoma were correlated with 5-year survival. Simple probability tests showed a significant prognostic difference of the presence or absence of cell borders, lymphocytic infiltration, pleomorphism of nuclei, and McNeal's typing. Further statistical analysis, with a probability test which was adjusted for the distribution of these factors, showed that only the presence or absence of cell borders and lymphocytic infiltration affected prognosis. It is very important for the pathologist reporting on prostate carcinoma to include mention of these factors in his report because of their prognostic importance. In particular it should be noted that if the tumor has indistinct cell borders and there is no lymphocytic infiltration, then it is likely to have a very poor prognosis."} {"id": "PMID:1260729", "title": "Risk for breast cancer development determined by mammographic parenchymal pattern.", "content": "A classification of risk for developing breast cancer has been devised based solely on the appearance of the breast parenchyma by mammography. Four groups of patients were isolated. The study encompassed a five-year period and was done by reviewing the mammograms of all women over the age of 30 who had been examined at Hutzel Hospital, Detroit. The average time of followup would be approximately 2 1/2 years. Four groups had an incidence of developing breast cancer of 0.1, 0.4, 1.7, and 2.2. These parenchymal patterns are described and criteria for their identification are given.", "contents": "Risk for breast cancer development determined by mammographic parenchymal pattern. A classification of risk for developing breast cancer has been devised based solely on the appearance of the breast parenchyma by mammography. Four groups of patients were isolated. The study encompassed a five-year period and was done by reviewing the mammograms of all women over the age of 30 who had been examined at Hutzel Hospital, Detroit. The average time of followup would be approximately 2 1/2 years. Four groups had an incidence of developing breast cancer of 0.1, 0.4, 1.7, and 2.2. These parenchymal patterns are described and criteria for their identification are given."} {"id": "PMID:1260730", "title": "Epithelial neoplasms of the vermiform appendix (exclusive of carcinoid). I. Adenocarcinoma of the appendix.", "content": "A study of primary epithelial neoplasms of the appendix (with the exception of classical carcinoids), produced 24 adenocarcinomas and 42 benign lesions from the files of the Laboratory of Surgical Pathology of Columbia University. Invasive adenoarcinomas were often complicated by appendicitis and were then unexpectedly discovered during appendectomy. In one third of the cases the carcinomas were found in juxtaposition to adenomatous lesions of the appendix. Well-differentiated adenocarcinomas of the colonic type generally had a better prognosis than signet-ring cell (or microglandular) tumors. The most reliable criterion for correlating prognosis was the Duke's method of staging. Since invasive adenocarcinomas of the appendix can metastasize to regional lymph nodes, treatment should ideally consist of ileocolectomy.", "contents": "Epithelial neoplasms of the vermiform appendix (exclusive of carcinoid). I. Adenocarcinoma of the appendix. A study of primary epithelial neoplasms of the appendix (with the exception of classical carcinoids), produced 24 adenocarcinomas and 42 benign lesions from the files of the Laboratory of Surgical Pathology of Columbia University. Invasive adenoarcinomas were often complicated by appendicitis and were then unexpectedly discovered during appendectomy. In one third of the cases the carcinomas were found in juxtaposition to adenomatous lesions of the appendix. Well-differentiated adenocarcinomas of the colonic type generally had a better prognosis than signet-ring cell (or microglandular) tumors. The most reliable criterion for correlating prognosis was the Duke's method of staging. Since invasive adenocarcinomas of the appendix can metastasize to regional lymph nodes, treatment should ideally consist of ileocolectomy."} {"id": "PMID:1260731", "title": "Epithelial neoplasms of the vermiform appendix (exclusive of carcinoid). II. Cystadenomas, papillary adenomas, and adenomatous polyps of the appendix.", "content": "Forty-two cases of benign epithelial neoplasms of the appendix gleaned from the files of the Laboratory of Surgical Pathology, Columbia University, were studied. The majority were associated with dilatation of the appendix, or \"mucocele.\" Conversely only 50% of all cystically dilated appendices examined had definite underlying adenomatous changes. Thus it is important to distinguish between cystic neoplasms (cystadenomas) and non-neoplastic retention cysts of the appendix. The most frequently found benign epithelial neoplasms were papillary adenomas. Even in the presence of atypia we labeled them benign. Appendectomy is usually adequate treatment for all adenomatous lesions occurring in the appendix. Almost a quarter of the cases reviewed were found to have synchronous or metachronous neoplasms elsewhere in the colon, while several patients harbored multiple colonic neoplasms in addition to the appendiceal adenomas. Thus a patient with an adenomatous lesion of the appendix should undergo a systematic search for other colonic lesions.", "contents": "Epithelial neoplasms of the vermiform appendix (exclusive of carcinoid). II. Cystadenomas, papillary adenomas, and adenomatous polyps of the appendix. Forty-two cases of benign epithelial neoplasms of the appendix gleaned from the files of the Laboratory of Surgical Pathology, Columbia University, were studied. The majority were associated with dilatation of the appendix, or \"mucocele.\" Conversely only 50% of all cystically dilated appendices examined had definite underlying adenomatous changes. Thus it is important to distinguish between cystic neoplasms (cystadenomas) and non-neoplastic retention cysts of the appendix. The most frequently found benign epithelial neoplasms were papillary adenomas. Even in the presence of atypia we labeled them benign. Appendectomy is usually adequate treatment for all adenomatous lesions occurring in the appendix. Almost a quarter of the cases reviewed were found to have synchronous or metachronous neoplasms elsewhere in the colon, while several patients harbored multiple colonic neoplasms in addition to the appendiceal adenomas. Thus a patient with an adenomatous lesion of the appendix should undergo a systematic search for other colonic lesions."} {"id": "PMID:1260732", "title": "Skin cancer and water arsenic in Lane County, Oregon.", "content": "It was expected that the incidence of skin cancer would be related to the known high arsenic levels in water supplies of Lane County, Oregon. Incidence rates were based on all histopathologically confirmed cases among Lane County residents diagnosed during 1958-1971 and were compared to mean water arsenic levels measured during 1968-1974. Basal cell carcinoma had a mean annual incidence rate of 88 per 100,000, a 5:4::M:F sex ratio, and an increasing risk for both sexes in urban areas. Squamous cell carcinoma incidence was 50 per 100,000 and showed 2:1:M:F sex ratio but no urban predilection. Neither type of skin cancer was directly related to the arsenic levels as expected, although sporadic individuals with sufficient exposure could manifest the relationship. Fewer than expected drinking water sources were found to contain high arsenic content, so that the Lane County data do not necessarily contradict previous reports of positive correlation. The basal cell carcinoma pattern suggested that this disease might be potentiated by urban air pollutants.", "contents": "Skin cancer and water arsenic in Lane County, Oregon. It was expected that the incidence of skin cancer would be related to the known high arsenic levels in water supplies of Lane County, Oregon. Incidence rates were based on all histopathologically confirmed cases among Lane County residents diagnosed during 1958-1971 and were compared to mean water arsenic levels measured during 1968-1974. Basal cell carcinoma had a mean annual incidence rate of 88 per 100,000, a 5:4::M:F sex ratio, and an increasing risk for both sexes in urban areas. Squamous cell carcinoma incidence was 50 per 100,000 and showed 2:1:M:F sex ratio but no urban predilection. Neither type of skin cancer was directly related to the arsenic levels as expected, although sporadic individuals with sufficient exposure could manifest the relationship. Fewer than expected drinking water sources were found to contain high arsenic content, so that the Lane County data do not necessarily contradict previous reports of positive correlation. The basal cell carcinoma pattern suggested that this disease might be potentiated by urban air pollutants."} {"id": "PMID:1260733", "title": "Cancer of the alimentary tract in the Sudan: a study of 546 cases.", "content": "Five hundred and forty-six primary malignant alimentary tract tumors in Sudanese patients are analyzed for frequency, age, sex, site, geographic distribution, and clinicopathologic presentations and are compared with other series. The disease is much less frequent in Sudan than in Western countries; within the Sudan itself it is much less prevalent in the South than the North. Generally, it tends to occur in younger age groups than in Western countries. Esophageal cancer is relatively common, especially in the Northern Province and has a female preponderance. Possible explanations are offered. Rectal cancer is more frequent than colonic cancer per se and occurs more often in males; more cases are recorded in relatively young patients. Colonic cancer has a predilection for the caecum. Alimentary cancer does not seem to be related to intestinal bilharziasis or other granulomas though these conditions may clinically mimic malignancy. The shortcomings in the collection of data are noted.", "contents": "Cancer of the alimentary tract in the Sudan: a study of 546 cases. Five hundred and forty-six primary malignant alimentary tract tumors in Sudanese patients are analyzed for frequency, age, sex, site, geographic distribution, and clinicopathologic presentations and are compared with other series. The disease is much less frequent in Sudan than in Western countries; within the Sudan itself it is much less prevalent in the South than the North. Generally, it tends to occur in younger age groups than in Western countries. Esophageal cancer is relatively common, especially in the Northern Province and has a female preponderance. Possible explanations are offered. Rectal cancer is more frequent than colonic cancer per se and occurs more often in males; more cases are recorded in relatively young patients. Colonic cancer has a predilection for the caecum. Alimentary cancer does not seem to be related to intestinal bilharziasis or other granulomas though these conditions may clinically mimic malignancy. The shortcomings in the collection of data are noted."} {"id": "PMID:1260734", "title": "On the diagnosis of minimal breast cancer in a screenee population.", "content": "As a result of screening of 8100 consecutive volunteers, 67 breast cancers have been detected. Fourteen percent of these cancers were found in women aged 35-44 years. Eighty percent of the cancers found in this age group were minimal breast cancer. This percentage decreased significantly in each subsequent decade until age 65 years, or older, when it began to rise once more. While mammography was responsible for detecting the majority of in situ or minimal cancers, 13 were found on physical examination, six of which were found only by physical examination.", "contents": "On the diagnosis of minimal breast cancer in a screenee population. As a result of screening of 8100 consecutive volunteers, 67 breast cancers have been detected. Fourteen percent of these cancers were found in women aged 35-44 years. Eighty percent of the cancers found in this age group were minimal breast cancer. This percentage decreased significantly in each subsequent decade until age 65 years, or older, when it began to rise once more. While mammography was responsible for detecting the majority of in situ or minimal cancers, 13 were found on physical examination, six of which were found only by physical examination."} {"id": "PMID:1260735", "title": "Fiberoptic coloscopy and cytology.", "content": "Colonic lavage for cytologic examination was obtained concomitantly with fiberoptic coloscopy during direct visualization of the affected bowe. Ninety-five patients were so studied. There were 61 benign lesions and 34 carcinomas. There were no false positives; abnormal cells were seen in 32 of the 34 carcinomas. It was concluded that this procedure might aid in an accurate histologic diagnosis; when biopsy was not possible, it could enhance the roentgenographic and endoscopic impression, and finally it might give a more complete diagnosis of the true lesion than small or subadjacent biopsies.", "contents": "Fiberoptic coloscopy and cytology. Colonic lavage for cytologic examination was obtained concomitantly with fiberoptic coloscopy during direct visualization of the affected bowe. Ninety-five patients were so studied. There were 61 benign lesions and 34 carcinomas. There were no false positives; abnormal cells were seen in 32 of the 34 carcinomas. It was concluded that this procedure might aid in an accurate histologic diagnosis; when biopsy was not possible, it could enhance the roentgenographic and endoscopic impression, and finally it might give a more complete diagnosis of the true lesion than small or subadjacent biopsies."} {"id": "PMID:1260739", "title": "Distribution of [3H]-3-hydroxykynurenine in mice.", "content": "The distribution of 3-hydroxykynurenine, a tryptophan metabolite that is suspected of being carcinogenic, was studied in mice. After s.c. administration of [3H]-3-hydroxykynurenine into male BALB/c X DBA/2 F1 mice, the distribution of 3H was investigated by whole-body autoradiography and radioactivity measurement. At 30 and 60 min after injection, 3H was distributed mainly in the kidneys, pancreas, liver, lung, and salivary glands. After 6 and 24 hr, 3H was retained only in the kidneys. After 30 min, about 70% of the radioactive compounds in the pancreas was unmetabolized 3-hydroxykynurenine, whereas most of the radioactivity in the kidneys, liver, lung, and submaxillary glands was derived from the other compounds. The data suggest that 3-hydroxykynurenine has an affinity for the pancreas.", "contents": "Distribution of [3H]-3-hydroxykynurenine in mice. The distribution of 3-hydroxykynurenine, a tryptophan metabolite that is suspected of being carcinogenic, was studied in mice. After s.c. administration of [3H]-3-hydroxykynurenine into male BALB/c X DBA/2 F1 mice, the distribution of 3H was investigated by whole-body autoradiography and radioactivity measurement. At 30 and 60 min after injection, 3H was distributed mainly in the kidneys, pancreas, liver, lung, and salivary glands. After 6 and 24 hr, 3H was retained only in the kidneys. After 30 min, about 70% of the radioactive compounds in the pancreas was unmetabolized 3-hydroxykynurenine, whereas most of the radioactivity in the kidneys, liver, lung, and submaxillary glands was derived from the other compounds. The data suggest that 3-hydroxykynurenine has an affinity for the pancreas."} {"id": "PMID:1260740", "title": "In vitro autoradiographic determination of cell kinetic parameters in adenocarcinomas and adjacent healthy mucosa of the human colon and rectum.", "content": "Using in vitro double labeling with two different doses of [3H]thymidine, we measured the S-phase duration and the labeling index in biopsy samples taken from human rectal and colonic adenocarcinomas. Samples from the adjacent healthy mucosa, taken at the same time as the tumor samples, were simultaneously subjected to the same measurements. The mean labeling index in tumors was higher than in the normal mucosa (32.5 and 17.0%, respectively). The mean S-phase value was also longer than in the normal tissue (19.4 versus 11.2 hr). These observations are discussed with reference to similar observations made in tumors of the human epidermis, especially considering the possible relationship of an increased S-phase duration with carcinogenesis. While no definitive conclusions may be reached, it seems prudent to consider an S-phase duration that is longer than normal to be a justification for attentive follow-up of the patient.", "contents": "In vitro autoradiographic determination of cell kinetic parameters in adenocarcinomas and adjacent healthy mucosa of the human colon and rectum. Using in vitro double labeling with two different doses of [3H]thymidine, we measured the S-phase duration and the labeling index in biopsy samples taken from human rectal and colonic adenocarcinomas. Samples from the adjacent healthy mucosa, taken at the same time as the tumor samples, were simultaneously subjected to the same measurements. The mean labeling index in tumors was higher than in the normal mucosa (32.5 and 17.0%, respectively). The mean S-phase value was also longer than in the normal tissue (19.4 versus 11.2 hr). These observations are discussed with reference to similar observations made in tumors of the human epidermis, especially considering the possible relationship of an increased S-phase duration with carcinogenesis. While no definitive conclusions may be reached, it seems prudent to consider an S-phase duration that is longer than normal to be a justification for attentive follow-up of the patient."} {"id": "PMID:1260741", "title": "Cellular kinetics and histological changes in experimental cancer of the uterine cervix.", "content": "Carcinoma of the mouse uterine cervix was induced by the insertion of 20-methylcholanthrene (MC) thread into the uterine cavity. Through biweekly observations, it was seen that the histopathological carcinogenesis in the cervix was characterized by three distinct changes: normal epithelium, anaplastic epithelium, and carcinoma. The incidence rate of normal epithelium declined sharply in the first 4 weeks, followed by slight decline up to the 20th week of observation. Nevertheless, about 20% of MC-treated mice maintained histologically normal epithelium even at the 20th week. In contrast, the incidence rate of anaplastic epithelium increased sharply in the first 4 weeks and thereafter tended to decline. Carcinoma was first observed at the 4th week, and its incidence rate increased thereafter almost linearly, reaching about 50% of the MC-treated mice at the 20th week. Carcinoma was divided into two groups, the early invasive and the frank invasive types. The former was further subgrouped into epithelial bud, nodular growth, epithelial cord, and mixed type by the mode of stromal invasion. Studies using [3H]thymidine autoradiography on the cell proliferation kinetics in the process of carcinoma development showed that a labeling index became higher as the malignant changes of the epithelium advanced. Moreover, S-phase prolongation was observed with the malignant changes, and the cell cycle time did not differ markedly among normal epithelium (22.8 hr), anaplastic epithelium (23.0 hr), and frank invasive carcinoma (26.1 hr). However, the growth fraction was greatly varied; it was 28% for normal epithelium, 61% for anaplastic epithelium, 100% for early invasive carcinoma, and 100% for frank invasive carcinoma. These results indicate that the growth fraction increases as the malignant changes in the MC-treated mouse uterine cervix.", "contents": "Cellular kinetics and histological changes in experimental cancer of the uterine cervix. Carcinoma of the mouse uterine cervix was induced by the insertion of 20-methylcholanthrene (MC) thread into the uterine cavity. Through biweekly observations, it was seen that the histopathological carcinogenesis in the cervix was characterized by three distinct changes: normal epithelium, anaplastic epithelium, and carcinoma. The incidence rate of normal epithelium declined sharply in the first 4 weeks, followed by slight decline up to the 20th week of observation. Nevertheless, about 20% of MC-treated mice maintained histologically normal epithelium even at the 20th week. In contrast, the incidence rate of anaplastic epithelium increased sharply in the first 4 weeks and thereafter tended to decline. Carcinoma was first observed at the 4th week, and its incidence rate increased thereafter almost linearly, reaching about 50% of the MC-treated mice at the 20th week. Carcinoma was divided into two groups, the early invasive and the frank invasive types. The former was further subgrouped into epithelial bud, nodular growth, epithelial cord, and mixed type by the mode of stromal invasion. Studies using [3H]thymidine autoradiography on the cell proliferation kinetics in the process of carcinoma development showed that a labeling index became higher as the malignant changes of the epithelium advanced. Moreover, S-phase prolongation was observed with the malignant changes, and the cell cycle time did not differ markedly among normal epithelium (22.8 hr), anaplastic epithelium (23.0 hr), and frank invasive carcinoma (26.1 hr). However, the growth fraction was greatly varied; it was 28% for normal epithelium, 61% for anaplastic epithelium, 100% for early invasive carcinoma, and 100% for frank invasive carcinoma. These results indicate that the growth fraction increases as the malignant changes in the MC-treated mouse uterine cervix."} {"id": "PMID:1260742", "title": "Iron homeostasis in plasmacytoma-bearing mice.", "content": "Plasmacytomas in mice have been shown to contain significant quantities of nonheme iron, half of which is in the form of ferritin. The livers of animals with plasmacytomas have a decreased iron content, and plasma iron is reduced. The animals develop an anemia that is partially corrected by parenteral iron. However, when plasmacytoma-bearing mice are given excessive amounts of parenteral iron, the surplus is stored in the liver of animals rather than in the tumor itself. These findings suggest that plasmacytomas sequester iron and deprive other organs of it to satisfy their own need. However, the tumors do not function as a storage site for iron above their own need.", "contents": "Iron homeostasis in plasmacytoma-bearing mice. Plasmacytomas in mice have been shown to contain significant quantities of nonheme iron, half of which is in the form of ferritin. The livers of animals with plasmacytomas have a decreased iron content, and plasma iron is reduced. The animals develop an anemia that is partially corrected by parenteral iron. However, when plasmacytoma-bearing mice are given excessive amounts of parenteral iron, the surplus is stored in the liver of animals rather than in the tumor itself. These findings suggest that plasmacytomas sequester iron and deprive other organs of it to satisfy their own need. However, the tumors do not function as a storage site for iron above their own need."} {"id": "PMID:1260743", "title": "A retinoic acid-binding protein from chick embryo skin.", "content": "Previous studies by others have indicated that retinoic acid reverses metaplastic changes caused by chemical caricinogens in vivo and in organ culture. The present study deals with the detection of a specific retinoic acid-binding protein from chick embryo metatarsal skin that may be mediating these biological effects. The protein has an S20 value of 2 and an isoelectric pH of 4.6. Competition experiments with labeled retinoic acid and 200-fold molar excesses of unlabeled retinoic acid, retinol, retinal, methyl retinoate, diethylretinamide, synthetic analogs of retinoic acid, and gamma-linolenic acid reveal that only retinoic acid and its analogs with a free carboxyl group bind to this protein. Among the analogs of retinoic acid, a cyclopentenyl analog, a trimethylmethoxyphenyl analog, 13-cis-retinoic acid, and alpha-retinoic acid compete for the binding site on the protein, with the cyclopentenyl analog having greater affinity than retinoic acid does. Phenyl and pyridyl analogs of retinoic acid are poor binders. In general, the ability of the various analgos to bind to this protein correlates with their biological activity in the reversal of keratinization and in the production of mucous metaplasia by chick embryo metatarsal skin as reported by others.", "contents": "A retinoic acid-binding protein from chick embryo skin. Previous studies by others have indicated that retinoic acid reverses metaplastic changes caused by chemical caricinogens in vivo and in organ culture. The present study deals with the detection of a specific retinoic acid-binding protein from chick embryo metatarsal skin that may be mediating these biological effects. The protein has an S20 value of 2 and an isoelectric pH of 4.6. Competition experiments with labeled retinoic acid and 200-fold molar excesses of unlabeled retinoic acid, retinol, retinal, methyl retinoate, diethylretinamide, synthetic analogs of retinoic acid, and gamma-linolenic acid reveal that only retinoic acid and its analogs with a free carboxyl group bind to this protein. Among the analogs of retinoic acid, a cyclopentenyl analog, a trimethylmethoxyphenyl analog, 13-cis-retinoic acid, and alpha-retinoic acid compete for the binding site on the protein, with the cyclopentenyl analog having greater affinity than retinoic acid does. Phenyl and pyridyl analogs of retinoic acid are poor binders. In general, the ability of the various analgos to bind to this protein correlates with their biological activity in the reversal of keratinization and in the production of mucous metaplasia by chick embryo metatarsal skin as reported by others."} {"id": "PMID:1260744", "title": "Induction of DNA polymerase alpha during liver regeneration in rats on controlled feeding schedules.", "content": "The activity of 2 nonmitochondrial forms of DNA polymerase, designated DNA polymerases alpha and beta, was investigated during liver regeneration in regimented rats. In accord with Barbiroli and Potter, we observed that regimentation of rats with respect to temperature, light and darkness, and availability of food resolves the DNA synthesis response to partial hepatectomy into 2 peaks, one occurring at a fixed time after operation and the other entrained by the environmental conditions. The peaks can be fused or separated depending on the timing of the operation. For this study, operation times were selected to give both patterns of DNA synthesis as measured by the uptake of radioactive thymidine into DNA. For both operation times, DNA polymerase activity in the nuclear extract correlated temporally and qualitatively with radioactive thymidine uptake into DNA. At the times of maximal DNA synthesis and polymerase activity, the DNA polymerase was purified from extracts of isolated nuclei. DNA polymerase alpha represented 70% and DNA polymerase beta represented 30% of the recovered activity from the nuclear extract. This is in agreement with the previous observation in nonregimented rats that DNA polymerase alpha is the major activity in nuclei during liver regeneration. For both operation times, DNA polymerase activity in the postmicrosomal fraction was sedimentable and increased 3 to 4 times above the level observed with this same fraction from normal rat liver. This activity was shown to be due to DNA polymerase alpha only with this subcellular fraction. DNA polymerase alpha activity with this fraction peaked 4 to 6 hr after the time of maximal radioactive thymidine incorporation into DNA. DNA polymerase activity in the microsome fraction did not change significantly after partial hepatectomy. This activity has been shown to represent DNA polymerase beta. Prior administration of cycloheximide and actinomycin abolished the rise in DNA polymerase alpha activity in the nucleus and postmicrosomal fraction. Hydroxyurea did not prevent the rise in DNA polymerase alpha activity with those subcellular fractions but did inhibit over 90% of the uptake of radioactive thymidine into DNA. These data suggest, but do not prove, that DNA polymerase alpha activity is induced in response to the stimulus(i) for liver regeneration.", "contents": "Induction of DNA polymerase alpha during liver regeneration in rats on controlled feeding schedules. The activity of 2 nonmitochondrial forms of DNA polymerase, designated DNA polymerases alpha and beta, was investigated during liver regeneration in regimented rats. In accord with Barbiroli and Potter, we observed that regimentation of rats with respect to temperature, light and darkness, and availability of food resolves the DNA synthesis response to partial hepatectomy into 2 peaks, one occurring at a fixed time after operation and the other entrained by the environmental conditions. The peaks can be fused or separated depending on the timing of the operation. For this study, operation times were selected to give both patterns of DNA synthesis as measured by the uptake of radioactive thymidine into DNA. For both operation times, DNA polymerase activity in the nuclear extract correlated temporally and qualitatively with radioactive thymidine uptake into DNA. At the times of maximal DNA synthesis and polymerase activity, the DNA polymerase was purified from extracts of isolated nuclei. DNA polymerase alpha represented 70% and DNA polymerase beta represented 30% of the recovered activity from the nuclear extract. This is in agreement with the previous observation in nonregimented rats that DNA polymerase alpha is the major activity in nuclei during liver regeneration. For both operation times, DNA polymerase activity in the postmicrosomal fraction was sedimentable and increased 3 to 4 times above the level observed with this same fraction from normal rat liver. This activity was shown to be due to DNA polymerase alpha only with this subcellular fraction. DNA polymerase alpha activity with this fraction peaked 4 to 6 hr after the time of maximal radioactive thymidine incorporation into DNA. DNA polymerase activity in the microsome fraction did not change significantly after partial hepatectomy. This activity has been shown to represent DNA polymerase beta. Prior administration of cycloheximide and actinomycin abolished the rise in DNA polymerase alpha activity in the nucleus and postmicrosomal fraction. Hydroxyurea did not prevent the rise in DNA polymerase alpha activity with those subcellular fractions but did inhibit over 90% of the uptake of radioactive thymidine into DNA. These data suggest, but do not prove, that DNA polymerase alpha activity is induced in response to the stimulus(i) for liver regeneration."} {"id": "PMID:1260745", "title": "The concentration of 67Ga and 45Ca in the lactating mammary gland and its relevance to the tumor uptake of 67Ga citrate.", "content": "67Ga is known to concentrate in the breasts of pregnant and postpartum women, and a case is now described in which 67Ga uptake was seen in the breasts of a woman who was neither pregnant nor postpartum, but was receiving chemotherapy for Hodgkin's disease. Comparative studies of the uptake of 67Ga and 45Ca in lactating dogs have shown that both nuclides are secreted in the milk in similar amounts and in protein-bound form. The concentration of 67Ga in mammary tissue is about one-half of that found in the milk at 5 hr postinjection but, by 48 hr, the concentrations are approximately equal. There were similarities in the subcellular distributions of 67Ga and 45Ca in the lactating mammary gland at 5 and 48 hr. Although there was a correlation between 67Ga and 45Ca in individual pieces of a lactating mammary gland at 5 hr after injection, no such correlation was seen between the two nuclides in multiple samples of a transmissible venereal tumor measured at various time intervals. The rate of dispersion of 67Ga and 45Ca from the lactating mammary gland was similar but, in the tumor, 67Ga was present in very much greater amounts than 45Ca and was retained longer. It is concluded that, although there may be similarities in the metabolic pathways of gallium and calcium in the lactating mammary gland, there is no similarity in the mechanism of uptake of these two elements into tumors.", "contents": "The concentration of 67Ga and 45Ca in the lactating mammary gland and its relevance to the tumor uptake of 67Ga citrate. 67Ga is known to concentrate in the breasts of pregnant and postpartum women, and a case is now described in which 67Ga uptake was seen in the breasts of a woman who was neither pregnant nor postpartum, but was receiving chemotherapy for Hodgkin's disease. Comparative studies of the uptake of 67Ga and 45Ca in lactating dogs have shown that both nuclides are secreted in the milk in similar amounts and in protein-bound form. The concentration of 67Ga in mammary tissue is about one-half of that found in the milk at 5 hr postinjection but, by 48 hr, the concentrations are approximately equal. There were similarities in the subcellular distributions of 67Ga and 45Ca in the lactating mammary gland at 5 and 48 hr. Although there was a correlation between 67Ga and 45Ca in individual pieces of a lactating mammary gland at 5 hr after injection, no such correlation was seen between the two nuclides in multiple samples of a transmissible venereal tumor measured at various time intervals. The rate of dispersion of 67Ga and 45Ca from the lactating mammary gland was similar but, in the tumor, 67Ga was present in very much greater amounts than 45Ca and was retained longer. It is concluded that, although there may be similarities in the metabolic pathways of gallium and calcium in the lactating mammary gland, there is no similarity in the mechanism of uptake of these two elements into tumors."} {"id": "PMID:1260746", "title": "Establishment of a human carcinoembryonic antigen-producing colon adenocarcinoma cell line.", "content": "A human carcinoembryonic antigen-producing colon carcinoma cell line has been established. The cells form acinar structures and signet ring cells. The lumen of the acini presents microvilli and a glycocalyx. Neighboring cells show desmosomes and terminal bars. The cells present an aneuploid karyotype with a modal number of 49. No marker chromosomes are found, although a significant proportion of cells show an altered A2 chromosome and an extra B. Exponentially growing cultures produce 54 ng of carcinoembryonic antigen/10(6) cells. Kinetic parameters are as follows: doubling time, 37 hr; mitotic index, 0.8%; labeling index, 31%; generation time, 30 hr; G1 phase, 7 hr; S phase, 18 hr; G2 phase, 5 hr; growth fraction 90%. This cell line, designated line LoVo, represents an in vitro model for human colon carcinoma.", "contents": "Establishment of a human carcinoembryonic antigen-producing colon adenocarcinoma cell line. A human carcinoembryonic antigen-producing colon carcinoma cell line has been established. The cells form acinar structures and signet ring cells. The lumen of the acini presents microvilli and a glycocalyx. Neighboring cells show desmosomes and terminal bars. The cells present an aneuploid karyotype with a modal number of 49. No marker chromosomes are found, although a significant proportion of cells show an altered A2 chromosome and an extra B. Exponentially growing cultures produce 54 ng of carcinoembryonic antigen/10(6) cells. Kinetic parameters are as follows: doubling time, 37 hr; mitotic index, 0.8%; labeling index, 31%; generation time, 30 hr; G1 phase, 7 hr; S phase, 18 hr; G2 phase, 5 hr; growth fraction 90%. This cell line, designated line LoVo, represents an in vitro model for human colon carcinoma."} {"id": "PMID:1260747", "title": "Potentiation of actinomycin D or adriamycin antitumor activity with DNA.", "content": "Several antitumor agents known to bind DNA were complexed with this macromolecule and tested for activity against experimental animal tumor systems. Combination studies with these agents and DNA were carried out at the same time. Actinomycin D activity against the P388 lymphocytic leukemia in BALB/c X DBA/2 F1 mice was significantly potentiated by calf thymus DNA, both when complexed and when injected in combination. The DNA could be given as much as 4 hr before or after the antibiotic and still give potentiation. Synergism was also obtained when the DNA was autoclaved prior to complexing and/or injecting. Similarly, adriamycin activity against the L1210 lymphoid leukemia in DBA/2 mice was significantly potentiated by autoclaved herring sperm DNA, both as a complex and when injected in combination. When above-optimal levels of adriamycin were complexed with autoclaved herring sperm DNA and injected into BALB/c mice inoculated with the Madison 109 alveogenic carcinoma, the early lethality was delayed and antitumor activity was sometimes observed. Herring sperm DNA injected alone also had antitumor activity against the Madison 109 tumor. Similarly, activity was obtained against this tumor system with calf thymus DNA and actinomycin D when injected alone. In addition, DNA, in combination and when complexed with actinomycin, prevented the toxicity observed with BALB/c mice, inoculated with the Madison 109 tumor, were given injections of an above-optimal dose of this antibiotic.", "contents": "Potentiation of actinomycin D or adriamycin antitumor activity with DNA. Several antitumor agents known to bind DNA were complexed with this macromolecule and tested for activity against experimental animal tumor systems. Combination studies with these agents and DNA were carried out at the same time. Actinomycin D activity against the P388 lymphocytic leukemia in BALB/c X DBA/2 F1 mice was significantly potentiated by calf thymus DNA, both when complexed and when injected in combination. The DNA could be given as much as 4 hr before or after the antibiotic and still give potentiation. Synergism was also obtained when the DNA was autoclaved prior to complexing and/or injecting. Similarly, adriamycin activity against the L1210 lymphoid leukemia in DBA/2 mice was significantly potentiated by autoclaved herring sperm DNA, both as a complex and when injected in combination. When above-optimal levels of adriamycin were complexed with autoclaved herring sperm DNA and injected into BALB/c mice inoculated with the Madison 109 alveogenic carcinoma, the early lethality was delayed and antitumor activity was sometimes observed. Herring sperm DNA injected alone also had antitumor activity against the Madison 109 tumor. Similarly, activity was obtained against this tumor system with calf thymus DNA and actinomycin D when injected alone. In addition, DNA, in combination and when complexed with actinomycin, prevented the toxicity observed with BALB/c mice, inoculated with the Madison 109 tumor, were given injections of an above-optimal dose of this antibiotic."} {"id": "PMID:1260748", "title": "Large bowel carcinogenesis in mice and rats by several intrarectal doses of methylnitrosourea and negative effect of nitrite plus methylurea.", "content": "The carcinogenic effect of several dose levels and regimens of an aqueous solution of N-methyl-N-nitrosourea (MNU) administered intrarectally to mice and rats is reported. In Ha/ICR Swiss mice, a single dose of 1.8 mg MNU induces mainly lymphomas and pulmonary tumors in less than 20 weeks. Repeated doses of 1.5 mg MNU induces lymphomas, pulmonary tumors, and also large bowel tumors in less than 20 weeks. Doses of 0.3 mg decreased the yield of lymphomas and increased large bowel neoplasms over a period of 40 to 60 weeks. Repeated doses of 0.06 mg also gave a low yield of lymphomas and large bowel tumors over a 60-week period. Thus, a maximal yield of lymphomas is seen with a brief regimen of high doses, whereas large bowel tumors occur with a more frequent lower dose rate. Male Fischer strain rats given 1.0 or 2.5 mg MNU 3 times a week for 10 weeks had a multiplicity of large bowel tumors, proportional to dose, in 25 to 30 weeks. In fact, the high dose level led to a 100% yield in less than 20 weeks. Lymphomas were seen only at the higher dose when the animals were were young, at the beginning of the test. In mice and rats the carcinomas were polypoid or plaque shaped and were well differentiated with extensive invasion but no metastases. The adenomas were pedunculated or sessile. Intrarectal administration of a mixture of methylurea and nitrite for 20 weeks and further observation of the rats for an additional 35 weeks yielded no colon tumors. Thus, there is indirect evidence of a lack of the in situ formation of carcinogenic MNU in the large bowel under physiological conditions.", "contents": "Large bowel carcinogenesis in mice and rats by several intrarectal doses of methylnitrosourea and negative effect of nitrite plus methylurea. The carcinogenic effect of several dose levels and regimens of an aqueous solution of N-methyl-N-nitrosourea (MNU) administered intrarectally to mice and rats is reported. In Ha/ICR Swiss mice, a single dose of 1.8 mg MNU induces mainly lymphomas and pulmonary tumors in less than 20 weeks. Repeated doses of 1.5 mg MNU induces lymphomas, pulmonary tumors, and also large bowel tumors in less than 20 weeks. Doses of 0.3 mg decreased the yield of lymphomas and increased large bowel neoplasms over a period of 40 to 60 weeks. Repeated doses of 0.06 mg also gave a low yield of lymphomas and large bowel tumors over a 60-week period. Thus, a maximal yield of lymphomas is seen with a brief regimen of high doses, whereas large bowel tumors occur with a more frequent lower dose rate. Male Fischer strain rats given 1.0 or 2.5 mg MNU 3 times a week for 10 weeks had a multiplicity of large bowel tumors, proportional to dose, in 25 to 30 weeks. In fact, the high dose level led to a 100% yield in less than 20 weeks. Lymphomas were seen only at the higher dose when the animals were were young, at the beginning of the test. In mice and rats the carcinomas were polypoid or plaque shaped and were well differentiated with extensive invasion but no metastases. The adenomas were pedunculated or sessile. Intrarectal administration of a mixture of methylurea and nitrite for 20 weeks and further observation of the rats for an additional 35 weeks yielded no colon tumors. Thus, there is indirect evidence of a lack of the in situ formation of carcinogenic MNU in the large bowel under physiological conditions."} {"id": "PMID:1260749", "title": "A comparison of the lethal effects of three nitrosourea derivatives on cultured human lymphoma cells.", "content": "The cellular effects of three nitrosourea derivatives were investigated on a human lymphoma cell line. The three drugs show similar threshold-type dose-response survival curves on asynchronous cells treated for 1 hr. Longer incubation periods result in rapid biological degradation for 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, remains cytotoxic after about 24 hr. Important differences were noted with respect to cell cycle dependency. The 1,3-bis(2-chloroethyl)-1-nitrosourea was more effective in early S and in G2 phase, whereas both 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea were more effective in early S. 1,3-bis(2-chlrorethyl)-1-nitrosourea exerted a considerable degree of killing in G1. Cells were unable to recover from priming damage induced by all 3 nitrosourea derivatives. No synergistic effects were observed in combination with vitamin A.", "contents": "A comparison of the lethal effects of three nitrosourea derivatives on cultured human lymphoma cells. The cellular effects of three nitrosourea derivatives were investigated on a human lymphoma cell line. The three drugs show similar threshold-type dose-response survival curves on asynchronous cells treated for 1 hr. Longer incubation periods result in rapid biological degradation for 1,3-bis(2-chloroethyl)-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas, 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea, remains cytotoxic after about 24 hr. Important differences were noted with respect to cell cycle dependency. The 1,3-bis(2-chloroethyl)-1-nitrosourea was more effective in early S and in G2 phase, whereas both 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-trans-4-methylcyclohexyl)-1-nitrosourea were more effective in early S. 1,3-bis(2-chlrorethyl)-1-nitrosourea exerted a considerable degree of killing in G1. Cells were unable to recover from priming damage induced by all 3 nitrosourea derivatives. No synergistic effects were observed in combination with vitamin A."} {"id": "PMID:1260750", "title": "Restriction of carcinogen-induced error incorporation during in vitro DNA synthesis.", "content": "The in vitro accuracy of DNA replication has been investigated through the measurement of the frequency with which noncomplementary nucleotides were incorporated during polynucleotide replication. The effect of beta-propiolactone treatment of deoxynucleotide templates, ribopolynucleotide templates, and the DNA polymerase from avian myeloblastosis virus was determined. Treatment of the deoxynucleotide template, poly(dA) (see article) oligo(dT) 12-18, by beta-propiolactone resulted in an increased frequency of noncomplementary nucleotide incorporation during DNA polymerization. Carcinogen treatment of the ribonucleotide templates, poly(rA) (see article) oligo(dT) 12-18, and poly(rC) (see article) oligo(dG) 12-18, and carcinogen treatment of avian myeloblastosis virus DNA polymerase did not alter the frequency of noncomplementary nucleotide incorporation. This suggested that carcinogen-induced error incorporation during DNA synthesis was restricted solely to the treatment of a deoxynucleotide template.", "contents": "Restriction of carcinogen-induced error incorporation during in vitro DNA synthesis. The in vitro accuracy of DNA replication has been investigated through the measurement of the frequency with which noncomplementary nucleotides were incorporated during polynucleotide replication. The effect of beta-propiolactone treatment of deoxynucleotide templates, ribopolynucleotide templates, and the DNA polymerase from avian myeloblastosis virus was determined. Treatment of the deoxynucleotide template, poly(dA) (see article) oligo(dT) 12-18, by beta-propiolactone resulted in an increased frequency of noncomplementary nucleotide incorporation during DNA polymerization. Carcinogen treatment of the ribonucleotide templates, poly(rA) (see article) oligo(dT) 12-18, and poly(rC) (see article) oligo(dG) 12-18, and carcinogen treatment of avian myeloblastosis virus DNA polymerase did not alter the frequency of noncomplementary nucleotide incorporation. This suggested that carcinogen-induced error incorporation during DNA synthesis was restricted solely to the treatment of a deoxynucleotide template."} {"id": "PMID:1260751", "title": "Mechanisms underlying reduced growth rate in C3HBA mammary adenocarcinomas recurring after single doses of x-rays or fast neutrons.", "content": "C3HBA mammary tumors were irradiated with 3000 rads of 250-kVp X-rays or 1000 rads of 8-MeV neutrons, doses of radiation matched for producing equal growth delay. At 14 days postirradiation, tumors were regrowing at a reduced rate relative to controls. Cell kinetic parameters were examined using percentage of labeled mitoses techniques, and blood vessel spacing and tumor architecture were examined histologically to determine whether the mechanisms underlying growth rate changes were the same after neutron as after photon irradiation. The tumor volume-doubling time at 14 days posttreatment is similar in both irradiated groups (TD=117 hr for neutron-irradiated tumors, 132 hr for X-irradiated tumors) and is approximately twice as long as the doubling time of 61.4 hr in control tumors in the same size range. Control and X-irradiated tumors have median cell cycle durations of 19.3 and 18.5 hr, respectively; the more slowly growing X-irradiated tumors have a reduced growth fraction and increased cell loss factor. Regrowing neutron-irradiated tumors have a median cell cycle of 27.2 hr, with calculated growth fraction and cell loss factor values intermediate between those for control and X-irradiated tumors. Scatter in the percentage of labeled mitoses data makes it difficult to determine whether the cell cycle durations are significantly different. The average distance from tumor parenchymal interphase cells to the nearest recognizable blood vessel is nearly identical in the two irradiated groups and for both groups is significantly greater than interphase to vessel distance in controls. The average distance in irradiated tumors approaches the maximal distance for O2 diffusion in mouse adenocarcinomas of a corded structure surrounding a central blood vessel. Both neutron- and X-irradiated tumors contain more necrosis and fewer viable-appearing parenchymal cells than do control tumors of the same size. The similar growth rate and growth delay in this tumor after 3000 rads of X-rays of 1000 rads of neutrons occur in the face of possibly different cell cycle durations and seem related to similar circulatory system inadequacies which limit growth and are expressed as greater average cell-to-blood-vessel distance and increased cell loss leading to necrosis, indicating oxygen or nutrient deprivation.", "contents": "Mechanisms underlying reduced growth rate in C3HBA mammary adenocarcinomas recurring after single doses of x-rays or fast neutrons. C3HBA mammary tumors were irradiated with 3000 rads of 250-kVp X-rays or 1000 rads of 8-MeV neutrons, doses of radiation matched for producing equal growth delay. At 14 days postirradiation, tumors were regrowing at a reduced rate relative to controls. Cell kinetic parameters were examined using percentage of labeled mitoses techniques, and blood vessel spacing and tumor architecture were examined histologically to determine whether the mechanisms underlying growth rate changes were the same after neutron as after photon irradiation. The tumor volume-doubling time at 14 days posttreatment is similar in both irradiated groups (TD=117 hr for neutron-irradiated tumors, 132 hr for X-irradiated tumors) and is approximately twice as long as the doubling time of 61.4 hr in control tumors in the same size range. Control and X-irradiated tumors have median cell cycle durations of 19.3 and 18.5 hr, respectively; the more slowly growing X-irradiated tumors have a reduced growth fraction and increased cell loss factor. Regrowing neutron-irradiated tumors have a median cell cycle of 27.2 hr, with calculated growth fraction and cell loss factor values intermediate between those for control and X-irradiated tumors. Scatter in the percentage of labeled mitoses data makes it difficult to determine whether the cell cycle durations are significantly different. The average distance from tumor parenchymal interphase cells to the nearest recognizable blood vessel is nearly identical in the two irradiated groups and for both groups is significantly greater than interphase to vessel distance in controls. The average distance in irradiated tumors approaches the maximal distance for O2 diffusion in mouse adenocarcinomas of a corded structure surrounding a central blood vessel. Both neutron- and X-irradiated tumors contain more necrosis and fewer viable-appearing parenchymal cells than do control tumors of the same size. The similar growth rate and growth delay in this tumor after 3000 rads of X-rays of 1000 rads of neutrons occur in the face of possibly different cell cycle durations and seem related to similar circulatory system inadequacies which limit growth and are expressed as greater average cell-to-blood-vessel distance and increased cell loss leading to necrosis, indicating oxygen or nutrient deprivation."} {"id": "PMID:1260752", "title": "Electron microscopic observations on the morphogenesis of renal cell carcinoma induced in rat kidney by dimethylnitrosamine and N-(3,5-dichlorophenyl)succinimide.", "content": "Renal cell carcinoma was induced in rats by p.o. administration of dimethylnitrosamine, 500 ppm daily, followed by N-(3,5-dichlorophenyl) succinimide (NDPS), 5000 ppm daily. Fine structural changes of the proximal convoluted tubule cells were observed by sequential examinations of the kidney cortices at 3, 5, 12, and 24 weeks after drug administration. Early prominent structural changes of the cells induced by dimethylnitrosamine alone were the appearance of microspherules in nucleoli and of numerous lamellar bodies on the membrane structure of the cells. With the addition of NDPS, the cells exhibited edematous cytoplasm that, in contrast to the relatively intact nuclear structure, contained numerous bodies small vesicles and dark mitochondria, with markedly disarranged microvilli. After prolonged treatment with these drugs, some of the cells showed regenerating features, while others became necrotic. In the former case, large clear nuclei appeared with enlarged nucleoli containing a large amount of granular components. Ribosomes in the cytoplasm also increased in number in accordance with nucleolar changes, and edema in cytoplasm and microvilli markedly decreased. However, a considerable number of vesicles still remained in some cells. Mitochondria decreased in number and showed pleomorphism and relatively high electron density. At 24 weeks, when clear cell carcinoma was induced, the cells in the cancer tissue exhibited a variety of features in their nuclei and cytoplasm. Some cells showed intact nuclear structure and dark cytoplasm containing a large number of vesicles; others had large round clear nuclei with enlarged nucleoli and clear cytoplasm containing no vesicles. Among these cells were mixed populations of large clear cells, showing a structure similar to the cells at 12 weeks, 2.e., to nodular hyperplastic cells. The starting point of malignant transformation seemed to be 1 week after treatment with NDPS (i.e., cells at 5 weeks) and, or the precancerous stage, at 12 weeks. These results suggest that the proximal convoluted tubule cells previously damaged by dimethylnitrosamine treatment were marked for mutation and were transformed to cancer cells by additional treatment with NDPS in such a way as to disturb the permeability of the membrane system of the cell and to condense chromatin fibers.", "contents": "Electron microscopic observations on the morphogenesis of renal cell carcinoma induced in rat kidney by dimethylnitrosamine and N-(3,5-dichlorophenyl)succinimide. Renal cell carcinoma was induced in rats by p.o. administration of dimethylnitrosamine, 500 ppm daily, followed by N-(3,5-dichlorophenyl) succinimide (NDPS), 5000 ppm daily. Fine structural changes of the proximal convoluted tubule cells were observed by sequential examinations of the kidney cortices at 3, 5, 12, and 24 weeks after drug administration. Early prominent structural changes of the cells induced by dimethylnitrosamine alone were the appearance of microspherules in nucleoli and of numerous lamellar bodies on the membrane structure of the cells. With the addition of NDPS, the cells exhibited edematous cytoplasm that, in contrast to the relatively intact nuclear structure, contained numerous bodies small vesicles and dark mitochondria, with markedly disarranged microvilli. After prolonged treatment with these drugs, some of the cells showed regenerating features, while others became necrotic. In the former case, large clear nuclei appeared with enlarged nucleoli containing a large amount of granular components. Ribosomes in the cytoplasm also increased in number in accordance with nucleolar changes, and edema in cytoplasm and microvilli markedly decreased. However, a considerable number of vesicles still remained in some cells. Mitochondria decreased in number and showed pleomorphism and relatively high electron density. At 24 weeks, when clear cell carcinoma was induced, the cells in the cancer tissue exhibited a variety of features in their nuclei and cytoplasm. Some cells showed intact nuclear structure and dark cytoplasm containing a large number of vesicles; others had large round clear nuclei with enlarged nucleoli and clear cytoplasm containing no vesicles. Among these cells were mixed populations of large clear cells, showing a structure similar to the cells at 12 weeks, 2.e., to nodular hyperplastic cells. The starting point of malignant transformation seemed to be 1 week after treatment with NDPS (i.e., cells at 5 weeks) and, or the precancerous stage, at 12 weeks. These results suggest that the proximal convoluted tubule cells previously damaged by dimethylnitrosamine treatment were marked for mutation and were transformed to cancer cells by additional treatment with NDPS in such a way as to disturb the permeability of the membrane system of the cell and to condense chromatin fibers."} {"id": "PMID:1260754", "title": "The sensitivity of the skin of hairless mice to chemical carcinogenesis.", "content": "The sensitivity of hairless mice to cutaneous chemical carcinogenesis has been compared with that of normal mice of the same strain with hair. A single application of 125 mug methylcholanthrene in benzene was given to 48 hairless male mice (hr/hr Oslo strain) and to 96 male mice of the same strain with hair. Among hairless mice there were 94% papilloma-bearing animals with a total of 5.9 tumors per animal after 18 months of observation, compared to 22% papilloma-bearing animals with an average of 0.3 tumors per animal among the mice with hair. The hairless mice included 31% carcinoma-bearing and 23% sarcoma-bearing animals, whereas only 1% of the mice with hair were carcinoma bearing and 3% were sarcoma bearing. Hairless mice of the hr/hr Oslo strain are thus not refractory to chemical carcinogenesis, but under the experimental conditions used in this study they are significantly more sensitive than are mice from the same strain with hair. Giovanella et al. reported almost opposite results in 1970 and came to the general conclusion that hairless mice are refractory to chemical carcinogenesis due to lack of hair follicles. Since hairless mice always have some hair follicles and rudimentary pilosebaceous appendages, comparisons between chemical carcinogenesis in hairless mice and mice with hair can neither strengthen nor weaken any theory about the hair follicle origin of epidermoid carcinomas of mouse skin.", "contents": "The sensitivity of the skin of hairless mice to chemical carcinogenesis. The sensitivity of hairless mice to cutaneous chemical carcinogenesis has been compared with that of normal mice of the same strain with hair. A single application of 125 mug methylcholanthrene in benzene was given to 48 hairless male mice (hr/hr Oslo strain) and to 96 male mice of the same strain with hair. Among hairless mice there were 94% papilloma-bearing animals with a total of 5.9 tumors per animal after 18 months of observation, compared to 22% papilloma-bearing animals with an average of 0.3 tumors per animal among the mice with hair. The hairless mice included 31% carcinoma-bearing and 23% sarcoma-bearing animals, whereas only 1% of the mice with hair were carcinoma bearing and 3% were sarcoma bearing. Hairless mice of the hr/hr Oslo strain are thus not refractory to chemical carcinogenesis, but under the experimental conditions used in this study they are significantly more sensitive than are mice from the same strain with hair. Giovanella et al. reported almost opposite results in 1970 and came to the general conclusion that hairless mice are refractory to chemical carcinogenesis due to lack of hair follicles. Since hairless mice always have some hair follicles and rudimentary pilosebaceous appendages, comparisons between chemical carcinogenesis in hairless mice and mice with hair can neither strengthen nor weaken any theory about the hair follicle origin of epidermoid carcinomas of mouse skin."} {"id": "PMID:1260755", "title": "Cell cycle dependency of human sarcoma-associated tumor antigen expression.", "content": "An analysis of cell cycle-dependent expression of tumor-associated antigen was performed on a human neurosarcoma cell line (T2 cells). The expression of sarcoma-associated tumor antigen on T2 cells was detected using test sera obtained from sarcoma patients; control sera were from patients with nonsarcoma neoplasias and from normal donors. Results indicate a progressive increase in the antigenic expression beginning in late mitosis and early G1 with maximum expression in mid-G1. Antigenic expression declines to minimum levels in S and G2-phase. Mechanisms responsible for this cycle-dependent fluctuation are presently unknown.", "contents": "Cell cycle dependency of human sarcoma-associated tumor antigen expression. An analysis of cell cycle-dependent expression of tumor-associated antigen was performed on a human neurosarcoma cell line (T2 cells). The expression of sarcoma-associated tumor antigen on T2 cells was detected using test sera obtained from sarcoma patients; control sera were from patients with nonsarcoma neoplasias and from normal donors. Results indicate a progressive increase in the antigenic expression beginning in late mitosis and early G1 with maximum expression in mid-G1. Antigenic expression declines to minimum levels in S and G2-phase. Mechanisms responsible for this cycle-dependent fluctuation are presently unknown."} {"id": "PMID:1260756", "title": "Effect of Corynebacterium parvum on the response to irradiation of a C3H fibrosarcoma.", "content": "A methylcholanthrene-induced fibrosarcoma of C3H mice has been used as 5th- to 6th-generation syngeneic transplant in an investigation of the role of Corynebacterium parvum as an adjuvant to the therapeutic effect of local irradiation of established tumors. The most effective route for administration of C. parvum in this tumor system was i.v., and the greatest effect of the C. parvum-mediated tumor graft rejection was observed for tumor growing intracutaneously or s.c. An intermediate level of effectiveness was obtained for tumor growing i.m. The combined C. parvum and local irradiation studies were performed using tumors growing in the leg muscle and measuring 8 mm in diameter at the time of local irradiation. Several routes of administration of C. parvum, dose levels of C. parvum, and time relationships between administration of C. parvum and irradiation were investigated. The outstanding finding was that very low doses of radiation were quite effective when administered to tumors growing in animals pretreated with C. parvum. This was true for radiation administered as a single or fractionated dose (10 equal doses spread over 18 days). For single-dose irradiation the effect was relatively dose independent over the range of 200 to 3000 rads. Some indication was obtained that local irradiation may impair the tumor graft rejection reaction. No evidence was obtained of an enhanced growth of tumor. Regression of tumor following irradiation was not modified by pretreatment with C. parvum. The mice that were unsuccessfully treated by radiation and C. parvum had a lower incidence of metastatic disease in the lung than did the mice treated unsuccessfully with radiation alone.", "contents": "Effect of Corynebacterium parvum on the response to irradiation of a C3H fibrosarcoma. A methylcholanthrene-induced fibrosarcoma of C3H mice has been used as 5th- to 6th-generation syngeneic transplant in an investigation of the role of Corynebacterium parvum as an adjuvant to the therapeutic effect of local irradiation of established tumors. The most effective route for administration of C. parvum in this tumor system was i.v., and the greatest effect of the C. parvum-mediated tumor graft rejection was observed for tumor growing intracutaneously or s.c. An intermediate level of effectiveness was obtained for tumor growing i.m. The combined C. parvum and local irradiation studies were performed using tumors growing in the leg muscle and measuring 8 mm in diameter at the time of local irradiation. Several routes of administration of C. parvum, dose levels of C. parvum, and time relationships between administration of C. parvum and irradiation were investigated. The outstanding finding was that very low doses of radiation were quite effective when administered to tumors growing in animals pretreated with C. parvum. This was true for radiation administered as a single or fractionated dose (10 equal doses spread over 18 days). For single-dose irradiation the effect was relatively dose independent over the range of 200 to 3000 rads. Some indication was obtained that local irradiation may impair the tumor graft rejection reaction. No evidence was obtained of an enhanced growth of tumor. Regression of tumor following irradiation was not modified by pretreatment with C. parvum. The mice that were unsuccessfully treated by radiation and C. parvum had a lower incidence of metastatic disease in the lung than did the mice treated unsuccessfully with radiation alone."} {"id": "PMID:1260757", "title": "Enhancement of a tumor allograft in BALB/c x DBA/2 F1 mice by pyran copolymer.", "content": "Pyran copolymer (NSC 46015) was evaluated with respect to its effect on the rejection of a murine leukemic allograft by BALB/c x DBA/2 F1 (CD2F1) mice. Significant prolongation of allograft survival with production of progressively growing lethal tumors was found following pyran administration. This phenomenon occurred at nontoxic doses of the drug and appeared to be closely related to the timing of pyran injection. Nonspecifically stimulated lymphocyte blast transformation by concanavalin A was not impaired by pyran when lymphocytes were exposed in vitro to the drug. The mechanism of tumor allograft enhancement remains obscure but may be related to allograft size at the time of pyran administration.", "contents": "Enhancement of a tumor allograft in BALB/c x DBA/2 F1 mice by pyran copolymer. Pyran copolymer (NSC 46015) was evaluated with respect to its effect on the rejection of a murine leukemic allograft by BALB/c x DBA/2 F1 (CD2F1) mice. Significant prolongation of allograft survival with production of progressively growing lethal tumors was found following pyran administration. This phenomenon occurred at nontoxic doses of the drug and appeared to be closely related to the timing of pyran injection. Nonspecifically stimulated lymphocyte blast transformation by concanavalin A was not impaired by pyran when lymphocytes were exposed in vitro to the drug. The mechanism of tumor allograft enhancement remains obscure but may be related to allograft size at the time of pyran administration."} {"id": "PMID:1260758", "title": "Urinary putrescine, spermidine, and spermine in human blood and solid cancers and in an experimental gastric tumor of rats.", "content": "An improved method of assay of urinary polyamines (putrescine, spermidine, and spermine) was applied to the study of cancer patients and an experimental gastric tumor of rats. Although total polyamines (putrescine, spermidine, and spermine) in urine of patients with blood and solid cancers were significantly high, putrescine concentrations also increased significantly and were shown to be of diagnostic aid even in solid cancers. A significant increase in putrescine was also noted in the urine of rats with experimental stomach tumors induced by N-methyl-N-nitro-N'-nitrosoguanidine.", "contents": "Urinary putrescine, spermidine, and spermine in human blood and solid cancers and in an experimental gastric tumor of rats. An improved method of assay of urinary polyamines (putrescine, spermidine, and spermine) was applied to the study of cancer patients and an experimental gastric tumor of rats. Although total polyamines (putrescine, spermidine, and spermine) in urine of patients with blood and solid cancers were significantly high, putrescine concentrations also increased significantly and were shown to be of diagnostic aid even in solid cancers. A significant increase in putrescine was also noted in the urine of rats with experimental stomach tumors induced by N-methyl-N-nitro-N'-nitrosoguanidine."} {"id": "PMID:1260759", "title": "Drug-mediated immunogenic changes of virus-induced leukemia in vivo.", "content": "LSTRA and RBL-5 lymphomas induced by Moloney and Rauscher leukemia viruses, respectively, were used to determine whether antigenically altered tumors induced by 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide in vivo would retain their original antigenic properties and/or have new antigenic properties. The tumors became highly immunogenic in the syngeneic hosts after 4 to 8 transplant generations with drug treatment. Syngeneic mice could be protected against challenge with the parental tumor by presensitization with the drug-altered sublines while unrelated tumor lines were incapable of protecting them. The drug-altered subline of LSTRA was used for treatment of the LSTRA in conjunction with chemotherapy, and this immunochemotherapy produced significant increases in number of survivors and increases in median survival time compared to either treatment alone. Tolerance studies indicated that there are novel antigens and parental tumor antigens associated with the drug-treated sublines.", "contents": "Drug-mediated immunogenic changes of virus-induced leukemia in vivo. LSTRA and RBL-5 lymphomas induced by Moloney and Rauscher leukemia viruses, respectively, were used to determine whether antigenically altered tumors induced by 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide in vivo would retain their original antigenic properties and/or have new antigenic properties. The tumors became highly immunogenic in the syngeneic hosts after 4 to 8 transplant generations with drug treatment. Syngeneic mice could be protected against challenge with the parental tumor by presensitization with the drug-altered sublines while unrelated tumor lines were incapable of protecting them. The drug-altered subline of LSTRA was used for treatment of the LSTRA in conjunction with chemotherapy, and this immunochemotherapy produced significant increases in number of survivors and increases in median survival time compared to either treatment alone. Tolerance studies indicated that there are novel antigens and parental tumor antigens associated with the drug-treated sublines."} {"id": "PMID:1260760", "title": "Growth control of heterologous tissue culture cells in the congenitally athymic nude mouse.", "content": "A variety of heterologous mammalian cells were inoculated into nude mice and scored for tumorigenicity. The cells tested were from primary cell cultures, established cell lines of neoplastic origin, established cell lines of nontumor origin, and primary cell cultures transformed by oncogenic viruses. Regardless of the animal species of origin, every cell line that was tumorigenic in some other animal host and every cell line of neoplastic origin was tumorigenic in nude mice. Several tissue culture cells lines capable of indefinite growth in vitro failed to form tumors in nude mice, and the basis of this growth suppression was investigated. The findings suggest that the failure of an established cell line to form tumors in nude mice is an authentic response to host-mediated growth-regulatory signals.", "contents": "Growth control of heterologous tissue culture cells in the congenitally athymic nude mouse. A variety of heterologous mammalian cells were inoculated into nude mice and scored for tumorigenicity. The cells tested were from primary cell cultures, established cell lines of neoplastic origin, established cell lines of nontumor origin, and primary cell cultures transformed by oncogenic viruses. Regardless of the animal species of origin, every cell line that was tumorigenic in some other animal host and every cell line of neoplastic origin was tumorigenic in nude mice. Several tissue culture cells lines capable of indefinite growth in vitro failed to form tumors in nude mice, and the basis of this growth suppression was investigated. The findings suggest that the failure of an established cell line to form tumors in nude mice is an authentic response to host-mediated growth-regulatory signals."} {"id": "PMID:1260761", "title": "Disease and non-disease-related cell-mediated cytotoxicity in humans.", "content": "The human bladder cancer/T24 system was used to investigate disease and non-disease-related cell-mediated cytotoxicity (CMC). CMC was determined in a modification of the microcytotoxicity assay of Takasugi and Klein. Analysis of data of groups of patients confirmed previous findings that effector cells (EC) from bladder cancer patients were more cytotoxic against T24 than were EC from normal individuals or from patients with other genitourinary cancers. Differences between patients with bladder cancer and other patients were not observed for other target cells. During the course of these experiments, non-disease-associated CMC by EC from individual normal donors and patients was observed. This phenomenon was investigated to determine its reproducibility and its relationship to different methods of preparing EC. Reproducibility of non-disease-related CMC was ascertained using EC prepared from heparinized blood by centrifugation over Ficoll-Hypaque (FH). A total of 126 experiments were performed in which 18 normal donors were tested 2 to 7 times each against 4 target cell lines. Of the resulting 46 combinations or groups of repeated assays, only 7 showed significant variability. Each normal donor had consistent CMC with differences from others being reproducible. CMC was therefore not due to crowding or physical effects. CMC mediated by EC prepared in this manner was then compared to that mediated by EC prepared by other methods in simultaneous tests.", "contents": "Disease and non-disease-related cell-mediated cytotoxicity in humans. The human bladder cancer/T24 system was used to investigate disease and non-disease-related cell-mediated cytotoxicity (CMC). CMC was determined in a modification of the microcytotoxicity assay of Takasugi and Klein. Analysis of data of groups of patients confirmed previous findings that effector cells (EC) from bladder cancer patients were more cytotoxic against T24 than were EC from normal individuals or from patients with other genitourinary cancers. Differences between patients with bladder cancer and other patients were not observed for other target cells. During the course of these experiments, non-disease-associated CMC by EC from individual normal donors and patients was observed. This phenomenon was investigated to determine its reproducibility and its relationship to different methods of preparing EC. Reproducibility of non-disease-related CMC was ascertained using EC prepared from heparinized blood by centrifugation over Ficoll-Hypaque (FH). A total of 126 experiments were performed in which 18 normal donors were tested 2 to 7 times each against 4 target cell lines. Of the resulting 46 combinations or groups of repeated assays, only 7 showed significant variability. Each normal donor had consistent CMC with differences from others being reproducible. CMC was therefore not due to crowding or physical effects. CMC mediated by EC prepared in this manner was then compared to that mediated by EC prepared by other methods in simultaneous tests."} {"id": "PMID:1260762", "title": "X-radiation-induced transformation in a C3H mouse embryo-derived cell line.", "content": "Reproducible X-ray-induced oncogenic transformation has been demonstrated in an established cell line of mouse embryo fibroblasts. Cells derived from transformed foci formed malignant tumors when injected into syngeneic hosts. An exponential increase in the number of transformants per viable cell occurred with doses of up to 400 rads of X-radiation. The transformation frequency in exponentially growing cultures remained constant at 2.3 x 10(-3) following doses of 400 to 1500 rads. There was little change in survival following X-ray doses up to 300 rads. Doses greater than 300 rads were associated with an exponential decline in survival; the Do for the survival curve was 175 rads. Transformation frequency varied with changes in the number of viable cells seeded per dish. There was about a 10-fold decline in the transformation frequency when the number of cells was increased from 400 to 1000 viable cells/100-mm Petri dish. Below this density range there was little change in transformation frequency. The presence of lethally preir-radiated cells was not associated with an enhancement of transformation in irradiated cells or with the induction of transformation in unirradiated cell cultures. Amphotericin B (Fungizone) inhibited the appearance of transformants when added to the culture medium within 2 to 3 weeks after initiation of the experiment.", "contents": "X-radiation-induced transformation in a C3H mouse embryo-derived cell line. Reproducible X-ray-induced oncogenic transformation has been demonstrated in an established cell line of mouse embryo fibroblasts. Cells derived from transformed foci formed malignant tumors when injected into syngeneic hosts. An exponential increase in the number of transformants per viable cell occurred with doses of up to 400 rads of X-radiation. The transformation frequency in exponentially growing cultures remained constant at 2.3 x 10(-3) following doses of 400 to 1500 rads. There was little change in survival following X-ray doses up to 300 rads. Doses greater than 300 rads were associated with an exponential decline in survival; the Do for the survival curve was 175 rads. Transformation frequency varied with changes in the number of viable cells seeded per dish. There was about a 10-fold decline in the transformation frequency when the number of cells was increased from 400 to 1000 viable cells/100-mm Petri dish. Below this density range there was little change in transformation frequency. The presence of lethally preir-radiated cells was not associated with an enhancement of transformation in irradiated cells or with the induction of transformation in unirradiated cell cultures. Amphotericin B (Fungizone) inhibited the appearance of transformants when added to the culture medium within 2 to 3 weeks after initiation of the experiment."} {"id": "PMID:1260763", "title": "Effect of vitamin A deficiency on rat colon carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine.", "content": "The effect of vitamin A deficiency on the sensitivity of the colon to the carcinogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting carcinogen, given intrarectally was studied in female Fischer rats. Animals maintained on Purina laboratory chow, semipurified vitamin A-free diet, or semipurified vitamine A-supplemented diet were given intrarectally 1.25, 0.63, or 0.31 mg MNNG 3 times weekly for 30 weeks and autopsied at the 45th week. The number of large bowel tumors per tumor-bearing rat was higher in animals receiving 1.25 mg MNNG compared to those given 0.63 or 0.31 mg. Vitamin A deficiency in rats given 1.25 mg MNNG significantly suppressed the large bowel tumor induction compared to rats fed adequate vitamin A. A high incidence of squamous cell papillomatosis of the urinary bladder was observed in rats fed vitamin A-free diet and given 1.25 mg MNNG. The present experiment suggests that the large intestine has a susceptibility that is different from that of the respiratory and urinary tracts to tumorigenic stimulation in vitamin A-deficient status.", "contents": "Effect of vitamin A deficiency on rat colon carcinogenesis by N-methyl-N'-nitro-N-nitrosoguanidine. The effect of vitamin A deficiency on the sensitivity of the colon to the carcinogenic effect of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a direct-acting carcinogen, given intrarectally was studied in female Fischer rats. Animals maintained on Purina laboratory chow, semipurified vitamin A-free diet, or semipurified vitamine A-supplemented diet were given intrarectally 1.25, 0.63, or 0.31 mg MNNG 3 times weekly for 30 weeks and autopsied at the 45th week. The number of large bowel tumors per tumor-bearing rat was higher in animals receiving 1.25 mg MNNG compared to those given 0.63 or 0.31 mg. Vitamin A deficiency in rats given 1.25 mg MNNG significantly suppressed the large bowel tumor induction compared to rats fed adequate vitamin A. A high incidence of squamous cell papillomatosis of the urinary bladder was observed in rats fed vitamin A-free diet and given 1.25 mg MNNG. The present experiment suggests that the large intestine has a susceptibility that is different from that of the respiratory and urinary tracts to tumorigenic stimulation in vitamin A-deficient status."} {"id": "PMID:1260764", "title": "DNA excision-repair deficiency of human peripheral blood lymphocytes treated with chemical carcinogens.", "content": "Human peripheral blood lymphocytes stimulated with concanavalin A for 72 hr have a 10-fold greater capacity to repair DNA damage induced by N-acetoxy-2-acetylaminofluorene than do unstimulated cells. The increased capacity of concanavalin A-activated cells to repair DNA is not observed after 24 hr in culture, a time at which stimulated cells have not begun to synthesize DNA. The maximum rate of repair synthesis obtained after treatment of stimulated cells with the \"large patch\"-inducing agent, N-acetoxy-2-acetylaminofluorene, is twice that obtained with methyl methanesulfonate, an agent inducing \"small patch\" repair. The difference between the maximum rates obtained with N-acetoxy-2-acetylaminofluorene and methyl methanesulfonate is 6-fold in a human lymphoblastoid line. Unstimulated lymphocytes show almost identical rates of repair after treatment with either N-acetoxy-2-acetylaminofluorene or methyl methanesulfonate. There is close correlation between the rate of N-acetoxy-2-acetylaminofluorene-induced repair synthesis and the loss of acetylaminofluorene adducts from DNA. Treatment of lymphocytes with methyl methanesulfonate leads to degradation of cellular DNA with the production of single-stranded regions. Such degradation is not observed with N-acetoxy-2-acetylaminofluroene. We conclude that the rate of excision repair is a function of the capacity of cells for DNA synthesis and that lymphocytes that do not synthesize DNA have a limited repair capacity and cannot be used to distinguish between large and small patch repair.", "contents": "DNA excision-repair deficiency of human peripheral blood lymphocytes treated with chemical carcinogens. Human peripheral blood lymphocytes stimulated with concanavalin A for 72 hr have a 10-fold greater capacity to repair DNA damage induced by N-acetoxy-2-acetylaminofluorene than do unstimulated cells. The increased capacity of concanavalin A-activated cells to repair DNA is not observed after 24 hr in culture, a time at which stimulated cells have not begun to synthesize DNA. The maximum rate of repair synthesis obtained after treatment of stimulated cells with the \"large patch\"-inducing agent, N-acetoxy-2-acetylaminofluorene, is twice that obtained with methyl methanesulfonate, an agent inducing \"small patch\" repair. The difference between the maximum rates obtained with N-acetoxy-2-acetylaminofluorene and methyl methanesulfonate is 6-fold in a human lymphoblastoid line. Unstimulated lymphocytes show almost identical rates of repair after treatment with either N-acetoxy-2-acetylaminofluorene or methyl methanesulfonate. There is close correlation between the rate of N-acetoxy-2-acetylaminofluorene-induced repair synthesis and the loss of acetylaminofluorene adducts from DNA. Treatment of lymphocytes with methyl methanesulfonate leads to degradation of cellular DNA with the production of single-stranded regions. Such degradation is not observed with N-acetoxy-2-acetylaminofluroene. We conclude that the rate of excision repair is a function of the capacity of cells for DNA synthesis and that lymphocytes that do not synthesize DNA have a limited repair capacity and cannot be used to distinguish between large and small patch repair."} {"id": "PMID:1260765", "title": "Chromosome patterns (G and C bands) of in vitro chemical carcinogen-transformed guinea pig cells.", "content": "The chromosomes of five chemical carcinogen-transformed strain 2 guinea pig fetal cell lines were identified by G and C banding techniques and were compared with the normal karyotype from secondary untreated cultures. One line transformed by benzo(a)pyrene had a diploid constitution with no G and C band alterations. Three lines were near diploid, one was near tetraploid, and each contained abnormal chromosomes. A 3-methylcholanthrene line had an abnormal metacentric chromosome formed by centric fusion of two nonhomologous autosomes. The three N-methyl-N'-nitrosoguanidine or diethylnitrosamine cell lines exhibited submetacentric or subtelocentric abnormal chromosomes originating from translocations between two No. 1 or a No. 1 and another autosome. The involvement of Chromosome 1 may be due to its association with nucleolar organization. The greater frequency of contact between such chromosomes, compared to other autosomes, creates an increased risk of chromatid exchange possibly explaining their frequent participation in abnormal chromosome formation or nondisjunction.", "contents": "Chromosome patterns (G and C bands) of in vitro chemical carcinogen-transformed guinea pig cells. The chromosomes of five chemical carcinogen-transformed strain 2 guinea pig fetal cell lines were identified by G and C banding techniques and were compared with the normal karyotype from secondary untreated cultures. One line transformed by benzo(a)pyrene had a diploid constitution with no G and C band alterations. Three lines were near diploid, one was near tetraploid, and each contained abnormal chromosomes. A 3-methylcholanthrene line had an abnormal metacentric chromosome formed by centric fusion of two nonhomologous autosomes. The three N-methyl-N'-nitrosoguanidine or diethylnitrosamine cell lines exhibited submetacentric or subtelocentric abnormal chromosomes originating from translocations between two No. 1 or a No. 1 and another autosome. The involvement of Chromosome 1 may be due to its association with nucleolar organization. The greater frequency of contact between such chromosomes, compared to other autosomes, creates an increased risk of chromatid exchange possibly explaining their frequent participation in abnormal chromosome formation or nondisjunction."} {"id": "PMID:1260766", "title": "Inhibition of tubulin-microtubule polymerization by drugs of the Vinca alkaloid class.", "content": "A series of Vinca alkaloids were found to block polymerization of crude tubulin extracts of porcine brain in a dose-dependent manner. This appears to be a specific effect occurring at low concentrations of drug. The concentration of vinblastine that prevents polymerization by 50% was 4.3 x 10(-7) mole/liter for a tubulin concentration of 3.0 mg/ml, and this concentration is consistent with levels achieved in vivo following routine pharmacological doses in humans.", "contents": "Inhibition of tubulin-microtubule polymerization by drugs of the Vinca alkaloid class. A series of Vinca alkaloids were found to block polymerization of crude tubulin extracts of porcine brain in a dose-dependent manner. This appears to be a specific effect occurring at low concentrations of drug. The concentration of vinblastine that prevents polymerization by 50% was 4.3 x 10(-7) mole/liter for a tubulin concentration of 3.0 mg/ml, and this concentration is consistent with levels achieved in vivo following routine pharmacological doses in humans."} {"id": "PMID:1260767", "title": "Production of melanoma-associated antigen(s) by a defined malignant melanoma cell strain grown in chemically defined medium.", "content": "A human malignant melanoma cell strain, UCLA-SO-M14 (M14), was adapted to grow in serum-free, chemically defined medium (CDM). The 3 M KCl extract prepared from the CDM-grown cells (M-14-CDM) was assayed against leukocytes from melanoma patients, patients with other cancers, and normal donors by leukocyte migration inhibition (LMI). The leukocytes from 15 to 27 (56%) melanoma patients tested were LMI positive. In contrast, 4 of 18 (22%) other cancer patients and 5 of 30 (17%) normal donors leukocytes were LMI positive. One of 14 melanoma patients' leukocytes were LMI positive for a control 3 M KCI extract from autologous muscle. Comparative studies were performed with the M14-CDM extract and a 3 M KCI extract from a freshly biopsied tumor specimen from the donor of the M14 cell strain. Seven of 12 (58%) melanoma patients' leukocytes were LMI positive to the M14-CDM extract, but only 2 of 12 (17%) were LMI positive to the autologous melanoma tissue extract. Furthermore, only 100 to 300 mug protein of M14-CDM extract were required to educe delayed cutaneous hypersensitivity response in 6 of 8 (75%) melanoma patients and 0 of 5 lung cancer patients, but 500 mug protein from biopsied autologous melanoma tissue extract were needed to produce delayed cutaneous hypersensitivity response in 24 of 42 (57%) melanoma patients and 7 of 28 (25%) nonmelanoma cancer patients. These data suggest: (a) the M14-CDM cells synthesized melanoma-associated antigen(s) (MAA) in CDM; (B) the 3 M KCI extraction procedure effectively removed the MAA from the M14-CDM cells; (c) the M14-CDM cells were a more potent source of MAA than the surgical autologous melanoma specimen; and (d) the M14-CDM cells provided a continuous source of standard MAA.", "contents": "Production of melanoma-associated antigen(s) by a defined malignant melanoma cell strain grown in chemically defined medium. A human malignant melanoma cell strain, UCLA-SO-M14 (M14), was adapted to grow in serum-free, chemically defined medium (CDM). The 3 M KCl extract prepared from the CDM-grown cells (M-14-CDM) was assayed against leukocytes from melanoma patients, patients with other cancers, and normal donors by leukocyte migration inhibition (LMI). The leukocytes from 15 to 27 (56%) melanoma patients tested were LMI positive. In contrast, 4 of 18 (22%) other cancer patients and 5 of 30 (17%) normal donors leukocytes were LMI positive. One of 14 melanoma patients' leukocytes were LMI positive for a control 3 M KCI extract from autologous muscle. Comparative studies were performed with the M14-CDM extract and a 3 M KCI extract from a freshly biopsied tumor specimen from the donor of the M14 cell strain. Seven of 12 (58%) melanoma patients' leukocytes were LMI positive to the M14-CDM extract, but only 2 of 12 (17%) were LMI positive to the autologous melanoma tissue extract. Furthermore, only 100 to 300 mug protein of M14-CDM extract were required to educe delayed cutaneous hypersensitivity response in 6 of 8 (75%) melanoma patients and 0 of 5 lung cancer patients, but 500 mug protein from biopsied autologous melanoma tissue extract were needed to produce delayed cutaneous hypersensitivity response in 24 of 42 (57%) melanoma patients and 7 of 28 (25%) nonmelanoma cancer patients. These data suggest: (a) the M14-CDM cells synthesized melanoma-associated antigen(s) (MAA) in CDM; (B) the 3 M KCI extraction procedure effectively removed the MAA from the M14-CDM cells; (c) the M14-CDM cells were a more potent source of MAA than the surgical autologous melanoma specimen; and (d) the M14-CDM cells provided a continuous source of standard MAA."} {"id": "PMID:1260768", "title": "Horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of the carcinogen N-hydroxy-N-acetyl-2-aminofluorene as effected by cyanide and ascorbate.", "content": "Horseradish peroxidase and H2O2 mediate N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) conversion into two more potent carcinogens, 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene. Optical studies of this system indicate that horseradish peroxidase is operating as a peroxidase with N-OH-AAF as the electron donor. Our studies confirm the earlier finding that 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene are the products of the type II enzyme-mediated oxidation of N-OH-AAF, but surprisingly, the results with the type VI enzyme indicate that more 2-nitrosofluorene was formed and, in addition, another product absorbing at 245 nm was formed. If ascorbate is present in the N-OH-AAF/horseradish peroxidase/H2O2 system, ascorbate is oxidized preferentially. Cyanide, a known inhibitor of the peroxidase, does not inhibit when N-OH-AAF is the electron donor. The reaction products are the same in the presence or absence of cyanide.", "contents": "Horseradish peroxidase/hydrogen peroxide-catalyzed oxidation of the carcinogen N-hydroxy-N-acetyl-2-aminofluorene as effected by cyanide and ascorbate. Horseradish peroxidase and H2O2 mediate N-hydroxy-N-acetyl-2-aminofluorene (N-OH-AAF) conversion into two more potent carcinogens, 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene. Optical studies of this system indicate that horseradish peroxidase is operating as a peroxidase with N-OH-AAF as the electron donor. Our studies confirm the earlier finding that 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene are the products of the type II enzyme-mediated oxidation of N-OH-AAF, but surprisingly, the results with the type VI enzyme indicate that more 2-nitrosofluorene was formed and, in addition, another product absorbing at 245 nm was formed. If ascorbate is present in the N-OH-AAF/horseradish peroxidase/H2O2 system, ascorbate is oxidized preferentially. Cyanide, a known inhibitor of the peroxidase, does not inhibit when N-OH-AAF is the electron donor. The reaction products are the same in the presence or absence of cyanide."} {"id": "PMID:1260769", "title": "Antileukemic effects of pseudoisocytidine, a new synthetic pyrimidine C-nucleoside.", "content": "Pseudoisocytidine, a new synthetic pyrimidine C-nucleoside, which might be considered a more stable analog of 5-azacytidine, is active in vitro and in vivo, i.p. and p.o., against various 1-beta-D-arabinofuranosylcytosine-resistant lines of mouse leukemia. This antileukemic activity is blocked by cytidine but not by deoxycytidine or thymidine.", "contents": "Antileukemic effects of pseudoisocytidine, a new synthetic pyrimidine C-nucleoside. Pseudoisocytidine, a new synthetic pyrimidine C-nucleoside, which might be considered a more stable analog of 5-azacytidine, is active in vitro and in vivo, i.p. and p.o., against various 1-beta-D-arabinofuranosylcytosine-resistant lines of mouse leukemia. This antileukemic activity is blocked by cytidine but not by deoxycytidine or thymidine."} {"id": "PMID:1260770", "title": "Experimental studies at Southern Research Institute with DTIC (NSC-45388).", "content": "Several years ago the diazotization of 5-aminoimidazole-4-carboxamide was found to give an internal diazonium salt, 5-diazoimidazole-4-carboxamide, which demonstrated marginal activity against some murine neoplasms. In an effort to improve this activity and develop a clinically useful agent, this compound was converted to a number of derivatives including DTIC, an agent that showed encouraging activity against a variety of rodent neoplasms. Studies carried out at Southern Research Institute on the chemistry, metabolism, and biologic activity of DTIC and its congeners are discussed briefly.", "contents": "Experimental studies at Southern Research Institute with DTIC (NSC-45388). Several years ago the diazotization of 5-aminoimidazole-4-carboxamide was found to give an internal diazonium salt, 5-diazoimidazole-4-carboxamide, which demonstrated marginal activity against some murine neoplasms. In an effort to improve this activity and develop a clinically useful agent, this compound was converted to a number of derivatives including DTIC, an agent that showed encouraging activity against a variety of rodent neoplasms. Studies carried out at Southern Research Institute on the chemistry, metabolism, and biologic activity of DTIC and its congeners are discussed briefly."} {"id": "PMID:1260780", "title": "Response to medroxyprogesterone acetate (NSC-26386) as secondary hormone therapy for metastatic breast cancer in postmenopausal women.", "content": "We have treated 40 postmenopausal women with documented metastatic breast cancer with medroxyprogesterone acetate. The average age was 63 years and the patients were, on the average, 14 years' postmenopausal. Only two patients had received no prior additive hormone therapy. The remainder had previously received estrogen, androgens, or both. Only two patients had objective evidence of tumor regression. In one patient a metastatic node disappeared for 7+ months, and the other patient had well-documented clinical improvement and control of brain mestastases for 22 months. Two other patients had mixed responses of chest wall metastases (regression of some but not all lesions), lasting 3 and 4 months respectively. Five other patients had obvious subjective benefit. There were four objective responses (10%) and five subjective responses (12%). There was no correlation between route of administration and response. All patients receiving benefit had previously responded to other hormones. Side effects were usually absent or consisted of mild fluid retention; however, four patients had disease stimulation from therapy.", "contents": "Response to medroxyprogesterone acetate (NSC-26386) as secondary hormone therapy for metastatic breast cancer in postmenopausal women. We have treated 40 postmenopausal women with documented metastatic breast cancer with medroxyprogesterone acetate. The average age was 63 years and the patients were, on the average, 14 years' postmenopausal. Only two patients had received no prior additive hormone therapy. The remainder had previously received estrogen, androgens, or both. Only two patients had objective evidence of tumor regression. In one patient a metastatic node disappeared for 7+ months, and the other patient had well-documented clinical improvement and control of brain mestastases for 22 months. Two other patients had mixed responses of chest wall metastases (regression of some but not all lesions), lasting 3 and 4 months respectively. Five other patients had obvious subjective benefit. There were four objective responses (10%) and five subjective responses (12%). There was no correlation between route of administration and response. All patients receiving benefit had previously responded to other hormones. Side effects were usually absent or consisted of mild fluid retention; however, four patients had disease stimulation from therapy."} {"id": "PMID:1260788", "title": "Synthesis of methyl alpha- and beta-D-xylopyranoside-5-18O.", "content": "Methyl alpha- and beta-D-xylopyranoside-5-18O (5 and 6) were prepared by way of oxygen exchange between 18O-water and the periodate-oxidation product (1) obtained from 1,2-O-isopropylidene-alpha-D-glucofuranose. The isotopic enrichment of 5 and 6 was determined by hydrolysis of each to D-xylose-5-18O (3), conversion of the sugar into 1,2,3,4-tetrakis-O-(tert-butyldimethylsilyl)-beta-D-xylopyranose-5-18O (7), and determination of the 18O content of the latter by use of a quadrupole, mass spectrometer.", "contents": "Synthesis of methyl alpha- and beta-D-xylopyranoside-5-18O. Methyl alpha- and beta-D-xylopyranoside-5-18O (5 and 6) were prepared by way of oxygen exchange between 18O-water and the periodate-oxidation product (1) obtained from 1,2-O-isopropylidene-alpha-D-glucofuranose. The isotopic enrichment of 5 and 6 was determined by hydrolysis of each to D-xylose-5-18O (3), conversion of the sugar into 1,2,3,4-tetrakis-O-(tert-butyldimethylsilyl)-beta-D-xylopyranose-5-18O (7), and determination of the 18O content of the latter by use of a quadrupole, mass spectrometer."} {"id": "PMID:1260789", "title": "Synthesis of 3-amino-2,3,6-trideoxy-D-ribo-hexose hydrochloride.", "content": "The title sugar, the 5-epimer of daunosamine, was prepared in a sequence of high-yielding steps from methyl alpha-D-mannopyranoside (1). Conversion of 1 into methyl 3-acetamido-4-O-benzoyl-6-bromo-2,3,6-trideoxy-alpha-D-ribo-hexopyranoside (2), followed by reduction with hydrogen and Raney nickel, gave the 4-benzoate (3) of methyl 3-acetamido-2,3,6-trideoxy-alpha-D-ribo-hexopyranoside (4). Saponification of 3 gave 4 as an oil that gave a crystalline 4-acetate (8). N-Deacetylation of 4 was effected with barium hydroxide, and the resultant glycoside was hydrolyzed to give 3-amino-2,3,6-trideoxy-D-ribo-hexose hydrochloride (7). The 3-benzamido analogue (5) of 4 was prepared from 4 by N-deacetylation and subsequent benzoylation, and hydrolysis of 5 gave crystalline 3-benzamido-2,3,6-trideoxy-D-ribo-hexose (6). The crystalline 3-acetamido analogue (9) of 6 was obtained by acid hydrolysis of the glycoside 4.", "contents": "Synthesis of 3-amino-2,3,6-trideoxy-D-ribo-hexose hydrochloride. The title sugar, the 5-epimer of daunosamine, was prepared in a sequence of high-yielding steps from methyl alpha-D-mannopyranoside (1). Conversion of 1 into methyl 3-acetamido-4-O-benzoyl-6-bromo-2,3,6-trideoxy-alpha-D-ribo-hexopyranoside (2), followed by reduction with hydrogen and Raney nickel, gave the 4-benzoate (3) of methyl 3-acetamido-2,3,6-trideoxy-alpha-D-ribo-hexopyranoside (4). Saponification of 3 gave 4 as an oil that gave a crystalline 4-acetate (8). N-Deacetylation of 4 was effected with barium hydroxide, and the resultant glycoside was hydrolyzed to give 3-amino-2,3,6-trideoxy-D-ribo-hexose hydrochloride (7). The 3-benzamido analogue (5) of 4 was prepared from 4 by N-deacetylation and subsequent benzoylation, and hydrolysis of 5 gave crystalline 3-benzamido-2,3,6-trideoxy-D-ribo-hexose (6). The crystalline 3-acetamido analogue (9) of 6 was obtained by acid hydrolysis of the glycoside 4."} {"id": "PMID:1260792", "title": "The importance of cuff width in measurement of blood pressure indirectly.", "content": "Blood pressure was measured indirectly in young adults with arm circumferences ranging from 21 to 35 cm using three standard blood pressure cuffs (thigh, adult, and child). The auscultatory method was used with Phase 1 and Phase V to indicate systolic and diastolic pressures respectively. It was found that use of the narrow cuff provided values higher than those obtained with the adult cuff; use of the thigh cuff produced value lower than those obtained with the adult cuff. These data, and a careful review of the literature, reveal the fundamental nature of the effect of the ratio of cuff width to member circumference with respect to the accuracy of indirect blood pressure measurements. The order of error expected with narrow and wide cuffs is discussed.", "contents": "The importance of cuff width in measurement of blood pressure indirectly. Blood pressure was measured indirectly in young adults with arm circumferences ranging from 21 to 35 cm using three standard blood pressure cuffs (thigh, adult, and child). The auscultatory method was used with Phase 1 and Phase V to indicate systolic and diastolic pressures respectively. It was found that use of the narrow cuff provided values higher than those obtained with the adult cuff; use of the thigh cuff produced value lower than those obtained with the adult cuff. These data, and a careful review of the literature, reveal the fundamental nature of the effect of the ratio of cuff width to member circumference with respect to the accuracy of indirect blood pressure measurements. The order of error expected with narrow and wide cuffs is discussed."} {"id": "PMID:1260791", "title": "Experimental barbiturate intoxication: treatment by partial cardiopulmonary bypass and hemodialysis.", "content": "1. The results of a series of experiments in which anesthetized mongrel dogs were instrumented and preparations for closed-chest partial cardiopulmonary bypass with membrane oxygenation and hemodialysis were made, following which \"fatal\" barbiturate intoxication was produced by the intravenous route has been presented. 2. Of nine animals, three (33 l/3%) could be removed from cardiopulmonary bypass although postoperative cardiovascular dynamics remained abnormal. 3. The clinical implications of this study in patients with cardiac depression in spite of hemodialysis for barbiturate intoxication seemed promising.", "contents": "Experimental barbiturate intoxication: treatment by partial cardiopulmonary bypass and hemodialysis. 1. The results of a series of experiments in which anesthetized mongrel dogs were instrumented and preparations for closed-chest partial cardiopulmonary bypass with membrane oxygenation and hemodialysis were made, following which \"fatal\" barbiturate intoxication was produced by the intravenous route has been presented. 2. Of nine animals, three (33 l/3%) could be removed from cardiopulmonary bypass although postoperative cardiovascular dynamics remained abnormal. 3. The clinical implications of this study in patients with cardiac depression in spite of hemodialysis for barbiturate intoxication seemed promising."} {"id": "PMID:1260829", "title": "Changes in the proliferation rate of mouse epidermis after irradiat-on continuous labelling studies.", "content": "The proliferative response of mouse skin to damage caused by X-irradiation has been tested by giving repeated injections of tritiated thymidine and scoring the percentage of labelled cells in high resolution autoradiography. Four, nine and fourteen daily fractions of 300 rads of X-rays were used and labelling commenced 4 days after the last fraction. The epidermis of the upper surface and the sole of the foot were scored separately and were compared with the skin of unirradiated feet. In unirradiated skin the proliferation rate of the basal layer cells is more rapid on the sole than on the upper surface. The cell cycle times deduced from continuous labelling curves were 81 hr and 111 hr respectively and the growth fractions were 97% and85%. After irradiation with small daily doses the homeostatic response to cell killing was slow. More rapid proliferation occurred after nine fractions in the sole, but was not apparent in the skin of the upper surface until fourteen fractions had been given. After fourteen fractions the cell cycle time was about 24 hr on both surfaces and the growth fraction was about 90%. The initial labelling index after a single thymidine injection was a poor measure of proliferation rate. The delay in the time of onset of faster proliferation is similar, both qualitatively and quantitatively, to that measured previously from the additional dose increments needed if large doses were given at different times after the multifraction treatments (Denekamp, 1973).", "contents": "Changes in the proliferation rate of mouse epidermis after irradiat-on continuous labelling studies. The proliferative response of mouse skin to damage caused by X-irradiation has been tested by giving repeated injections of tritiated thymidine and scoring the percentage of labelled cells in high resolution autoradiography. Four, nine and fourteen daily fractions of 300 rads of X-rays were used and labelling commenced 4 days after the last fraction. The epidermis of the upper surface and the sole of the foot were scored separately and were compared with the skin of unirradiated feet. In unirradiated skin the proliferation rate of the basal layer cells is more rapid on the sole than on the upper surface. The cell cycle times deduced from continuous labelling curves were 81 hr and 111 hr respectively and the growth fractions were 97% and85%. After irradiation with small daily doses the homeostatic response to cell killing was slow. More rapid proliferation occurred after nine fractions in the sole, but was not apparent in the skin of the upper surface until fourteen fractions had been given. After fourteen fractions the cell cycle time was about 24 hr on both surfaces and the growth fraction was about 90%. The initial labelling index after a single thymidine injection was a poor measure of proliferation rate. The delay in the time of onset of faster proliferation is similar, both qualitatively and quantitatively, to that measured previously from the additional dose increments needed if large doses were given at different times after the multifraction treatments (Denekamp, 1973)."} {"id": "PMID:1260830", "title": "A serum facted by newborn calf serum.", "content": "An intraperitoneal injection of newborn calf serum (NBCS) into CRF Swiss mice causes an inflammatory reaction characterized by an increase in the number of macrophages in the peritoneal cavity and a concomitant monocytosis. The serum of such mice contains a monocytosis-inducing factor, as demonstrated by the intravenous injection of serum collected 18 (CalS18) and 24 hr (CalS24) after the intraperitoneal injection of NBCS. Serum from normal untreated mice, from mice given an intraperitoneal injection of sterile pyrogen-free saline, which does not cause an inflammatory reaction, or from mice 72 hr after an intraperitoneal injection of NBCS, when the inflammatory reaction has subsided, does not cause a monocytosis in test mice. Intravenous injection of CalS18 causes not only a monocytosis but also an increase in the number of promonocytes and bone marrow monocytes, suggesting an increased in the number of promonocytes and bone marrow monocytes, suggesting an increased production of monocytes. The effect of CalS18, CalS24 and CalS18 filtrate is specific for the mononuclear phagocytes, since only non-significant increases in the numbers of lymphocytes and granulocytes were observed. The active factor in CalS18 was shown to be different from the monocytosis-inducing factor present in NBCS. The monocytosis-inducing factor in CalS18 passes through an ultrafiltration membrane with an exclusion limit of 50,000 Daltons, so that the molecular weight must be below this value.", "contents": "A serum facted by newborn calf serum. An intraperitoneal injection of newborn calf serum (NBCS) into CRF Swiss mice causes an inflammatory reaction characterized by an increase in the number of macrophages in the peritoneal cavity and a concomitant monocytosis. The serum of such mice contains a monocytosis-inducing factor, as demonstrated by the intravenous injection of serum collected 18 (CalS18) and 24 hr (CalS24) after the intraperitoneal injection of NBCS. Serum from normal untreated mice, from mice given an intraperitoneal injection of sterile pyrogen-free saline, which does not cause an inflammatory reaction, or from mice 72 hr after an intraperitoneal injection of NBCS, when the inflammatory reaction has subsided, does not cause a monocytosis in test mice. Intravenous injection of CalS18 causes not only a monocytosis but also an increase in the number of promonocytes and bone marrow monocytes, suggesting an increased in the number of promonocytes and bone marrow monocytes, suggesting an increased production of monocytes. The effect of CalS18, CalS24 and CalS18 filtrate is specific for the mononuclear phagocytes, since only non-significant increases in the numbers of lymphocytes and granulocytes were observed. The active factor in CalS18 was shown to be different from the monocytosis-inducing factor present in NBCS. The monocytosis-inducing factor in CalS18 passes through an ultrafiltration membrane with an exclusion limit of 50,000 Daltons, so that the molecular weight must be below this value."} {"id": "PMID:1260831", "title": "The influence of 400 r x-irradiation on the number and the localization of mature and immature goblet cells and Paneth cells in intestinal crypt and villus.", "content": "The influence of 400 R X-irradiation on the localization and the number of mature and immature goblet cells and Paneth cells in rat duodenal epithelium has been studied. At short times after irradiation, when the total proliferative activity in the crypts of Lieberkuhn is reduced, the proportion of mature and immature goblet cells of the total number of crypt cells was increased; also an absolute increase in the number of goblet cells in the crypts was found. The immature goblet cells were localized in the lower half of the crypt as in control animals, whereas the number of the mature cells increased over the whole crypt length. When the proliferative activity of the crypt cells increases again from 12 to 48 hr after irradiation the number of both types of goblet cells decreases. Between 48 and 72 hr, when the whole crypt is involved in proliferation, a second increase of both types of goblet cells was found. However, the localization of the immature goblet cells is no longer restricted to the lower half of the crypt but they also appear at the higher cell positions. On the villus no immature goblet cells were found and the changes in the numbers of mature goblet cells do reflect the changes induced by irradiation in the goblet cell population in the crypt. The absolute number and localization of Paneth cells did not change under the experimental conditions. The findings are discussed in relation to cell proliferation and differentiation processes in intestinal crypts.", "contents": "The influence of 400 r x-irradiation on the number and the localization of mature and immature goblet cells and Paneth cells in intestinal crypt and villus. The influence of 400 R X-irradiation on the localization and the number of mature and immature goblet cells and Paneth cells in rat duodenal epithelium has been studied. At short times after irradiation, when the total proliferative activity in the crypts of Lieberkuhn is reduced, the proportion of mature and immature goblet cells of the total number of crypt cells was increased; also an absolute increase in the number of goblet cells in the crypts was found. The immature goblet cells were localized in the lower half of the crypt as in control animals, whereas the number of the mature cells increased over the whole crypt length. When the proliferative activity of the crypt cells increases again from 12 to 48 hr after irradiation the number of both types of goblet cells decreases. Between 48 and 72 hr, when the whole crypt is involved in proliferation, a second increase of both types of goblet cells was found. However, the localization of the immature goblet cells is no longer restricted to the lower half of the crypt but they also appear at the higher cell positions. On the villus no immature goblet cells were found and the changes in the numbers of mature goblet cells do reflect the changes induced by irradiation in the goblet cell population in the crypt. The absolute number and localization of Paneth cells did not change under the experimental conditions. The findings are discussed in relation to cell proliferation and differentiation processes in intestinal crypts."} {"id": "PMID:1260832", "title": "Recycling of resting cells in the JB-1 ascites tumour after treatment with 1-beta-D-arabinofuranosylcytosine (ara-C).", "content": "Resting cells in tumours present a major problem in cancer chemotherapy. In the plateau phase of grwoth of the murine JB-1 ascites tumour (i.e. 10 days after 2-5 X 10(6) cells i.p.) large fractions of non-cycling cells with G1 and G2 DNA content (Q1 and Q2 cells) are present, and the fate of these resting cells was investigated after treatment with 1-beta-D-arabinofuranosylcytosine (Ara-C). The experimental work of growth curves, percentage of labelled mitoses curves after continuous labelling with 3H-TdR, and cytophotometric determination of single-cell DNA content in unlabelled tumour cells. Treatment with an i.p. single injection of Ara-C 200 mg/kg in the plateau JB-1 tumour resulted in a significant reduction in the number of tumour cells 1 and 2 days later as compared with untreated controls, while no difference in the number of tumour cells was observed after 3 days. In tumours prelabelled with 3H-TdR 24 hr before Ara-C treatment, a significant decrease in the percentage of labelled mitoses was observed 6-8 hr later followed by a return to the initial value after 12 hr, and a new pronounced fall from 20 hr after Ara-C. The second fall in the percentage of labelled mitoses disappeared when the labelling with 3H-TdR was continued also after Ara-C treatment. Cytophotometry of unlabelled tumour cells prelabelled for 24 hr with 3H-TdR before Ara-C treatment showed 20 hr after Ara-C a pronounced decrease in the fraction of Q1 cells paralleled by an increase in the fraction of unlabelled cells with S DNA content. The results indicate recycling of resting cells first with G2 and later with G1 DNA content, which contribute to the regrowth of the tumours.", "contents": "Recycling of resting cells in the JB-1 ascites tumour after treatment with 1-beta-D-arabinofuranosylcytosine (ara-C). Resting cells in tumours present a major problem in cancer chemotherapy. In the plateau phase of grwoth of the murine JB-1 ascites tumour (i.e. 10 days after 2-5 X 10(6) cells i.p.) large fractions of non-cycling cells with G1 and G2 DNA content (Q1 and Q2 cells) are present, and the fate of these resting cells was investigated after treatment with 1-beta-D-arabinofuranosylcytosine (Ara-C). The experimental work of growth curves, percentage of labelled mitoses curves after continuous labelling with 3H-TdR, and cytophotometric determination of single-cell DNA content in unlabelled tumour cells. Treatment with an i.p. single injection of Ara-C 200 mg/kg in the plateau JB-1 tumour resulted in a significant reduction in the number of tumour cells 1 and 2 days later as compared with untreated controls, while no difference in the number of tumour cells was observed after 3 days. In tumours prelabelled with 3H-TdR 24 hr before Ara-C treatment, a significant decrease in the percentage of labelled mitoses was observed 6-8 hr later followed by a return to the initial value after 12 hr, and a new pronounced fall from 20 hr after Ara-C. The second fall in the percentage of labelled mitoses disappeared when the labelling with 3H-TdR was continued also after Ara-C treatment. Cytophotometry of unlabelled tumour cells prelabelled for 24 hr with 3H-TdR before Ara-C treatment showed 20 hr after Ara-C a pronounced decrease in the fraction of Q1 cells paralleled by an increase in the fraction of unlabelled cells with S DNA content. The results indicate recycling of resting cells first with G2 and later with G1 DNA content, which contribute to the regrowth of the tumours."} {"id": "PMID:1260833", "title": "Mode of growth of the jejunal crypt cells of the rat: an autoradiographic study using double labelling with 3H- and 14C-thymidine in lower and upper parts of crypts.", "content": "The frequency distribution of cells through the mitotic cycle in lower and upper portions of jejunal crypts of the rat was examined by the 3H-14C-thymidine double labelling technique. Isolated crypts were cut perpendicular to the longitudinal axis so that the percentage of cells in the lower portion varied from 16 to 74%. The lower and upper portion of the same crypt were squashed separately on one microscope slide and the number of 3H- and 14C-only labelled cells were scored to determine the flow rate into and out of S for the two portions. The mitotic cycle and its phases of the crypt epithelial cells were also determined. For lower portions of crypts which contained less than 40% of the total cell number in that crypt the flow rate into S was about 1-7 times that of the flow rate out of S indicating that nearly every mitosis in this region produced two proliferative daughter cells. As the proportion of cells in the lower part of the crypt increased the quotient of the flow rate into S divided by the flow rate out of S decreased, and approached the steady state value of 1-0 in lower portions containing 60-74% of the cells. For upper portions of crypts which contained less than 40% of the total crypt cells the flow rate into S was about 0-2 times that of the flow rate out of S, indicating that in this region mitoses predominantly produced non-proliferative daughter cells. The results obtained were in good agreement with the model of crypt cell proliferation proposed by Cairnie, Lamerton & Steel (1965b).", "contents": "Mode of growth of the jejunal crypt cells of the rat: an autoradiographic study using double labelling with 3H- and 14C-thymidine in lower and upper parts of crypts. The frequency distribution of cells through the mitotic cycle in lower and upper portions of jejunal crypts of the rat was examined by the 3H-14C-thymidine double labelling technique. Isolated crypts were cut perpendicular to the longitudinal axis so that the percentage of cells in the lower portion varied from 16 to 74%. The lower and upper portion of the same crypt were squashed separately on one microscope slide and the number of 3H- and 14C-only labelled cells were scored to determine the flow rate into and out of S for the two portions. The mitotic cycle and its phases of the crypt epithelial cells were also determined. For lower portions of crypts which contained less than 40% of the total cell number in that crypt the flow rate into S was about 1-7 times that of the flow rate out of S indicating that nearly every mitosis in this region produced two proliferative daughter cells. As the proportion of cells in the lower part of the crypt increased the quotient of the flow rate into S divided by the flow rate out of S decreased, and approached the steady state value of 1-0 in lower portions containing 60-74% of the cells. For upper portions of crypts which contained less than 40% of the total crypt cells the flow rate into S was about 0-2 times that of the flow rate out of S, indicating that in this region mitoses predominantly produced non-proliferative daughter cells. The results obtained were in good agreement with the model of crypt cell proliferation proposed by Cairnie, Lamerton & Steel (1965b)."} {"id": "PMID:1260834", "title": "Study of cell death in Friend leukaemia.", "content": "Cell death of splenic Friend leukaemic cells has been studied in vivo, using 125I-UdR and 3H-TdR pulse labelling. The evolution of the splenic specific activity has been measured by autoradiography and external counting during 40 hr after injection of the labelled precursor. These two techniques show the existence of a large reutilization of 3H-TdR (50%), which is measurable as soon as 7 hr after the injection. The DNA turnover rate is rapid, 83-8% of the splenic cellular DNA being renewed per day. Those results confirm that most of the cells produced in the Friend leukaemic spleen are rapidly lost; they also demonstrate that this cell loss is mainly due to a massive death, which occurs in proerythroblastic and erythroblastic compartments after one or two cell divisions. Friend leukaemic cells, which are characterized by a limited capacity of proliferation and a short lifespan, do not appear to be malignant.", "contents": "Study of cell death in Friend leukaemia. Cell death of splenic Friend leukaemic cells has been studied in vivo, using 125I-UdR and 3H-TdR pulse labelling. The evolution of the splenic specific activity has been measured by autoradiography and external counting during 40 hr after injection of the labelled precursor. These two techniques show the existence of a large reutilization of 3H-TdR (50%), which is measurable as soon as 7 hr after the injection. The DNA turnover rate is rapid, 83-8% of the splenic cellular DNA being renewed per day. Those results confirm that most of the cells produced in the Friend leukaemic spleen are rapidly lost; they also demonstrate that this cell loss is mainly due to a massive death, which occurs in proerythroblastic and erythroblastic compartments after one or two cell divisions. Friend leukaemic cells, which are characterized by a limited capacity of proliferation and a short lifespan, do not appear to be malignant."} {"id": "PMID:1260835", "title": "The cell proliferation kinetics of the EMT6/M/AC mouse tumour at four volumes during unperturbed growth in vivo.", "content": "The cell proliferation kinetics of the EMT6/M/AC mouse tumour were determined at four different volumes between 1-5 mm3 and 175 mm3. The decrease in the growth rate between these volumes are mainly due to a decrease in the rate constant for cell production. A small increase in the rate constant for cell loss occurred, but this was thought to be insignificant. The cell loss factor increased from 40% at 1-5 mm3 to over 70% in the 175 mm3 tumours. An increase in the median cell cycle time, from 14-1 hr to 18-5 hr was also found between these same volumes. Results obtained for the NCTC fibrosarcoma and the R-1 rhabdo-myosarcoms indicate that there may be a threshold volume in these sarcomas below which little or no cell loss takes place. This was not found in the EMT6/M/AC tumour.", "contents": "The cell proliferation kinetics of the EMT6/M/AC mouse tumour at four volumes during unperturbed growth in vivo. The cell proliferation kinetics of the EMT6/M/AC mouse tumour were determined at four different volumes between 1-5 mm3 and 175 mm3. The decrease in the growth rate between these volumes are mainly due to a decrease in the rate constant for cell production. A small increase in the rate constant for cell loss occurred, but this was thought to be insignificant. The cell loss factor increased from 40% at 1-5 mm3 to over 70% in the 175 mm3 tumours. An increase in the median cell cycle time, from 14-1 hr to 18-5 hr was also found between these same volumes. Results obtained for the NCTC fibrosarcoma and the R-1 rhabdo-myosarcoms indicate that there may be a threshold volume in these sarcomas below which little or no cell loss takes place. This was not found in the EMT6/M/AC tumour."} {"id": "PMID:1260836", "title": "Characteristics of the isoprenaline stimulated proliferative response of rat submaxillary gland.", "content": "A simple stochastic model has been developed to determine the cell cycle kinetics of the isoprenaline stimulated proliferative response in rat acinar cells. The response was measured experimentally, using 3H-TdR labelling of interphase cells and cumulative collections of mitotic cells with vincristine. The rise and fall of the fraction of labelled interphase cells and of metaphase cells is expressed by the product of the proliferative fraction and a difference of probability distributions. The probability statements of the model were formulated and then compared by an iterative fitting procedure to experimental data to obtain estimates of the model parameters. The model when fitted to the combined fraction labelled interphase (FLIW) and fraction metaphase (FMWa) waves gave a mean Gis transit time of 21-2 hr, mean Gis +S transit time of 27-0 hr, and mean Gis + S + G2 transit time of 35-8 hr for a single injection of isoprenaline, where Gis is the initiation to S phase time. When successive injections of isoprenaline were given at intervals of 24 and 28 hr the corresponding values after the third injection were 12-4 hr, 20-8 hr and 25-7 hr respectively. The variance of the Gis phase dropped from 18-1 to 1-3 while the other variances remained unchanged. The estimated proliferative fraction was 0-24 after a single injection of isoprenaline, and 0.31 after three injections of the drug. Independently determined values of the proliferative fraction, obtained from repeated 3H-TdR injections, were 0-21 and 0-36 respectively.", "contents": "Characteristics of the isoprenaline stimulated proliferative response of rat submaxillary gland. A simple stochastic model has been developed to determine the cell cycle kinetics of the isoprenaline stimulated proliferative response in rat acinar cells. The response was measured experimentally, using 3H-TdR labelling of interphase cells and cumulative collections of mitotic cells with vincristine. The rise and fall of the fraction of labelled interphase cells and of metaphase cells is expressed by the product of the proliferative fraction and a difference of probability distributions. The probability statements of the model were formulated and then compared by an iterative fitting procedure to experimental data to obtain estimates of the model parameters. The model when fitted to the combined fraction labelled interphase (FLIW) and fraction metaphase (FMWa) waves gave a mean Gis transit time of 21-2 hr, mean Gis +S transit time of 27-0 hr, and mean Gis + S + G2 transit time of 35-8 hr for a single injection of isoprenaline, where Gis is the initiation to S phase time. When successive injections of isoprenaline were given at intervals of 24 and 28 hr the corresponding values after the third injection were 12-4 hr, 20-8 hr and 25-7 hr respectively. The variance of the Gis phase dropped from 18-1 to 1-3 while the other variances remained unchanged. The estimated proliferative fraction was 0-24 after a single injection of isoprenaline, and 0.31 after three injections of the drug. Independently determined values of the proliferative fraction, obtained from repeated 3H-TdR injections, were 0-21 and 0-36 respectively."} {"id": "PMID:1260837", "title": "Preferential labeling of rat lymphocytes with a rapid rate of turnover by tritiated deoxycytidine.", "content": "Lymphocytes in thymic cortex and germinal centers of lymphoid tissues are labeled intensely with generally labeled tritiated deoxycytidine [G-3H]dCyd whereas they are weakly labeled with methyl tritiated deosythymidine [methyl3H]dThd of the same specific activity, not only by single injection but also by an intensive injection schedule. [G-3H]dCyd can be used to label short-lived lymphocytes strongly, although not specifically. The distribution patterns of labeled lymphocytes were different depending on the injection schedules of [G-3H]dCyd. [G-3H]dCyd can be used as a precursor molecule for cytosine and also thymine found in DNA. The ratios of radioactive thymine to crytosine measured biochemically on DNA extracted from radioactive lymphocytes labeled by the various schedules indicate strongly that short- and long-lived lymphocyte populations have different abilities to utilize pyrimidine nucleosides for DNA synthesis.", "contents": "Preferential labeling of rat lymphocytes with a rapid rate of turnover by tritiated deoxycytidine. Lymphocytes in thymic cortex and germinal centers of lymphoid tissues are labeled intensely with generally labeled tritiated deoxycytidine [G-3H]dCyd whereas they are weakly labeled with methyl tritiated deosythymidine [methyl3H]dThd of the same specific activity, not only by single injection but also by an intensive injection schedule. [G-3H]dCyd can be used to label short-lived lymphocytes strongly, although not specifically. The distribution patterns of labeled lymphocytes were different depending on the injection schedules of [G-3H]dCyd. [G-3H]dCyd can be used as a precursor molecule for cytosine and also thymine found in DNA. The ratios of radioactive thymine to crytosine measured biochemically on DNA extracted from radioactive lymphocytes labeled by the various schedules indicate strongly that short- and long-lived lymphocyte populations have different abilities to utilize pyrimidine nucleosides for DNA synthesis."} {"id": "PMID:1260838", "title": "The predominant role of the spleen in lymphocyte recirculation. II. Pre- and postsplenectomy retransfusion studies in young pigs.", "content": "Autologous blood lymphocytes from three normal pigs were labelled with 3H-uridine and retransfused before and after splenectomy. Frequent samples for up to 150 min after retransfusion were evaluated autoradiographically to determine the rate of disappearance of labelled lymphocytes from the blood. In one pig retransfusion was performed before and after sham-splenectomy. In all preoperative experiments the pattern of disappearance of labelled lymphocytes was very similar. After a first rapid decline (halving time on average 8 min) a short rise of the labelling index was observed from 10 to 15 min after retransfusion. Then a second more gradual decrease of labelled lymphocytes followed. The mean halving time during this period was less than 32 min. From 60 min onwards the labelling index remained nearly constant. Retransfusions performed 3 days after splenectomy revealed only one nearly constant decline of the labelling index (halving time on average 129 min). After sham-splenectomy the pattern of disappearance was similar to the preoperative experiment. One hour after the end of retransfusion the labelling index had decreased by three-quarters of the initial value in normal pigs and by only one-third in the splenectomized ones. These results indicate that in the pig the total rate of recirculation is at least 4 times faster with the spleen in situ than without the spleen.", "contents": "The predominant role of the spleen in lymphocyte recirculation. II. Pre- and postsplenectomy retransfusion studies in young pigs. Autologous blood lymphocytes from three normal pigs were labelled with 3H-uridine and retransfused before and after splenectomy. Frequent samples for up to 150 min after retransfusion were evaluated autoradiographically to determine the rate of disappearance of labelled lymphocytes from the blood. In one pig retransfusion was performed before and after sham-splenectomy. In all preoperative experiments the pattern of disappearance of labelled lymphocytes was very similar. After a first rapid decline (halving time on average 8 min) a short rise of the labelling index was observed from 10 to 15 min after retransfusion. Then a second more gradual decrease of labelled lymphocytes followed. The mean halving time during this period was less than 32 min. From 60 min onwards the labelling index remained nearly constant. Retransfusions performed 3 days after splenectomy revealed only one nearly constant decline of the labelling index (halving time on average 129 min). After sham-splenectomy the pattern of disappearance was similar to the preoperative experiment. One hour after the end of retransfusion the labelling index had decreased by three-quarters of the initial value in normal pigs and by only one-third in the splenectomized ones. These results indicate that in the pig the total rate of recirculation is at least 4 times faster with the spleen in situ than without the spleen."} {"id": "PMID:1260839", "title": "Cell proliferation in the erythroid compartment of guinea-pig bone marrow: studies with 3H-thymidine.", "content": "Single and multiple injections of 3H-TdR have been used for measuring the rate of proliferation in morphologically defined cell populations of guinea-pig bone marrow that are committed to erythroid differentiation. The conclusions are based on the analysis of absolute cell numbers in the maturational compartments, the labeling and mitotic indices, labeled mitotic curves, pulse and chase grain counts over dividing and interphase cells, and on the rate or labeling during multiple, repeated injections of 3H-TdR. The average duration of S and the rate of cycling is similar in all maturational compartments of the erythrom. The majority of cells progress to the next maturational compartment by the time they divide for the second time. All proerythroblasts and basophilic erythroblasts are in cycle. Polychromatic erythroblasts incapable of incorporating 3H-TdR reach the orthochromatic population in the span of 5-6 hr. The orthochromatic population is renewed every 20-24 hr. The number of divisions between the proerythroblast and orthochromatic erythroblast does not exceed four and some cells may undergo only two divisions during the maturation pathway. Cell input from a progenitor cell population contributes to the maintenance of the erythron. The kinetic behavior of progenitor cells is similar to that of proerythroblasts. By the time of their second division, progenitor cells may reach either the proerythroblast or basophilic erythroblast compartments. The kinetic behavior of basophilic transitional cells corresponds to the predicted behavior of the erythroblast progenitor cell pool. Several of the conclusions are based on the assumption that grain count halving is the result of cell division. In view of the evidence discussed, this assumption in the present studies seems justified.", "contents": "Cell proliferation in the erythroid compartment of guinea-pig bone marrow: studies with 3H-thymidine. Single and multiple injections of 3H-TdR have been used for measuring the rate of proliferation in morphologically defined cell populations of guinea-pig bone marrow that are committed to erythroid differentiation. The conclusions are based on the analysis of absolute cell numbers in the maturational compartments, the labeling and mitotic indices, labeled mitotic curves, pulse and chase grain counts over dividing and interphase cells, and on the rate or labeling during multiple, repeated injections of 3H-TdR. The average duration of S and the rate of cycling is similar in all maturational compartments of the erythrom. The majority of cells progress to the next maturational compartment by the time they divide for the second time. All proerythroblasts and basophilic erythroblasts are in cycle. Polychromatic erythroblasts incapable of incorporating 3H-TdR reach the orthochromatic population in the span of 5-6 hr. The orthochromatic population is renewed every 20-24 hr. The number of divisions between the proerythroblast and orthochromatic erythroblast does not exceed four and some cells may undergo only two divisions during the maturation pathway. Cell input from a progenitor cell population contributes to the maintenance of the erythron. The kinetic behavior of progenitor cells is similar to that of proerythroblasts. By the time of their second division, progenitor cells may reach either the proerythroblast or basophilic erythroblast compartments. The kinetic behavior of basophilic transitional cells corresponds to the predicted behavior of the erythroblast progenitor cell pool. Several of the conclusions are based on the assumption that grain count halving is the result of cell division. In view of the evidence discussed, this assumption in the present studies seems justified."} {"id": "PMID:1260840", "title": "Studies on intracellular transport of secretory proteins in the rat exocrine pancreas. IV. Stimulation by in vivo infusion of caerulein.", "content": "Prolonged secretory stimulation of the exocrine pancreas in the rat by in vivo infusion of caerulein leads to a rapid degranulation of the organ associated with a progressive reduction in the size of the zymogen granules. During the first six to twelve hours of stimulation Golgi complexes are enlarged and several structural forms of multivesicular bodies are found indicating a lysosomal degradation of membrane material in the Golgi area. Maximum secretory activity is obtained after a 24 hour infusion, Golgi complexes appear fragmented, the secretory granules measure only 1/3 to 1/4 their normal size. Thereafter, in spite of a continuous stimulation, the exocrine cells regranulate progressively up to 72 hours of infusion. This regranulation is associated with massive enlargement of the Golgi complexes.", "contents": "Studies on intracellular transport of secretory proteins in the rat exocrine pancreas. IV. Stimulation by in vivo infusion of caerulein. Prolonged secretory stimulation of the exocrine pancreas in the rat by in vivo infusion of caerulein leads to a rapid degranulation of the organ associated with a progressive reduction in the size of the zymogen granules. During the first six to twelve hours of stimulation Golgi complexes are enlarged and several structural forms of multivesicular bodies are found indicating a lysosomal degradation of membrane material in the Golgi area. Maximum secretory activity is obtained after a 24 hour infusion, Golgi complexes appear fragmented, the secretory granules measure only 1/3 to 1/4 their normal size. Thereafter, in spite of a continuous stimulation, the exocrine cells regranulate progressively up to 72 hours of infusion. This regranulation is associated with massive enlargement of the Golgi complexes."} {"id": "PMID:1260842", "title": "Synaptology of the rat suprachiasmatic nucleus.", "content": "Within the suprachiasmatic nucleus (SCN) of the rat the fine structure of the synapses and some features of their topological arrangement were studied. Five types of synapses could be distinguished with certainty: A. Two types of Gray-type-I (GTI) or asymmetrical synapses (approximately 33%). The presynaptic elements contain strikingly different types of mitochondria. Size of clear vesicles: approximately 450 A. Synapses with subjunctional bodies often occur, among these also \"crest synapses\". Localization: dendritic shafts and spines, rarely somata. B. Three types of Gray-type-2 (GTII) or symmetrical synapses (approximately 66%):1) Axo-dendritic and -somatic (=AD) synapses. Size of clear vesicles: approximately 500 A. 2) Invaginated axo-dendritic and -somatic (=IAD) synapses with club-like postsynaptic protrusions within the presynaptic elements (PreE1). Size of clear vesicles is very variable: approximately 400-1,000 A. 3) Dendro-dendritic, -somatic and somato-dendritic (=DD) synapses occurring at least partly in reciprocal arrangements. They represent an intrinsic system. Shape of clear vesicles: often oval; sucrose treatment partly produces flattening. Dense core-vesicles (dcv) are found in all GTII- and most of the GTI-synapses after three-dimensional reconstruction. All types of synapses (mostly GTII-synapses) can be enclosed by multilamellar astroglial formations. The synapses often occur in complex synaptic arrangements. Dendrites and somata of females show significantly more multivesiculated bodies than those of males. Further pecularities of presynaptic (PreELs) and postsynaptic elements (PostELs) within the SCN are described and discussed.", "contents": "Synaptology of the rat suprachiasmatic nucleus. Within the suprachiasmatic nucleus (SCN) of the rat the fine structure of the synapses and some features of their topological arrangement were studied. Five types of synapses could be distinguished with certainty: A. Two types of Gray-type-I (GTI) or asymmetrical synapses (approximately 33%). The presynaptic elements contain strikingly different types of mitochondria. Size of clear vesicles: approximately 450 A. Synapses with subjunctional bodies often occur, among these also \"crest synapses\". Localization: dendritic shafts and spines, rarely somata. B. Three types of Gray-type-2 (GTII) or symmetrical synapses (approximately 66%):1) Axo-dendritic and -somatic (=AD) synapses. Size of clear vesicles: approximately 500 A. 2) Invaginated axo-dendritic and -somatic (=IAD) synapses with club-like postsynaptic protrusions within the presynaptic elements (PreE1). Size of clear vesicles is very variable: approximately 400-1,000 A. 3) Dendro-dendritic, -somatic and somato-dendritic (=DD) synapses occurring at least partly in reciprocal arrangements. They represent an intrinsic system. Shape of clear vesicles: often oval; sucrose treatment partly produces flattening. Dense core-vesicles (dcv) are found in all GTII- and most of the GTI-synapses after three-dimensional reconstruction. All types of synapses (mostly GTII-synapses) can be enclosed by multilamellar astroglial formations. The synapses often occur in complex synaptic arrangements. Dendrites and somata of females show significantly more multivesiculated bodies than those of males. Further pecularities of presynaptic (PreELs) and postsynaptic elements (PostELs) within the SCN are described and discussed."} {"id": "PMID:1260841", "title": "Chromaffin, small granule-containing and ganglion cells in the adrenal gland of reptiles: A comparative ultrastructural study.", "content": "Chromaffin, small granule-containing (SGC)-cells, neurons and the innervation of these cells was studied in the adrenal gland of three species of reptiles (Testudo graeca, Lacerta dugesi, Natrix natrix). 1. After fixation with glutaraldehyde and osmium-tetroxide adrenaline (A)- and noradrenaline (NA)-storing cells can be distinguished by means of the different electron density of their granules: A-granules are moderately electron-dense, while NA-granules show a core of high electron density. The unusually high electron density of a few A-granules in Testudo occasionally required viewing of unstained sections which facilitated the discrimination of the two cell types in this species. In all species studied NA-granules display a remarkable polymorphism which is most pronounced in the tortoise. In this species A-granules are polymorphic, too. Both types of granules show wide variations in size, which are particularly great in the tortoise. This species also exhibits the largest average sizes for A-granules (285 nm), and NA-granules (354 nm). The corresponding parameters for Lacerta and Natrix, are 255 and 179 nm for A- and 323 and 304 nm for NA-granules, respectively. The rough ER in A-cells of the tortoise regularly occurs in the form of circular dilations ('ergastosomes', Kanerva and Hervonen, 1973). Mitochondria sometimes contain longitudinal cristae with a crystalloid internal pattern. Large dense bodies which incorporate granules are abundant in NA-cells. Smaller dense bodies containing a few dense patches and membranes are present in both A- and NA-cells. Intermediate stages between dense bodies and what appear to be A- or NA-granules (if the latter have lost some of their amine-content) are frequently observed.", "contents": "Chromaffin, small granule-containing and ganglion cells in the adrenal gland of reptiles: A comparative ultrastructural study. Chromaffin, small granule-containing (SGC)-cells, neurons and the innervation of these cells was studied in the adrenal gland of three species of reptiles (Testudo graeca, Lacerta dugesi, Natrix natrix). 1. After fixation with glutaraldehyde and osmium-tetroxide adrenaline (A)- and noradrenaline (NA)-storing cells can be distinguished by means of the different electron density of their granules: A-granules are moderately electron-dense, while NA-granules show a core of high electron density. The unusually high electron density of a few A-granules in Testudo occasionally required viewing of unstained sections which facilitated the discrimination of the two cell types in this species. In all species studied NA-granules display a remarkable polymorphism which is most pronounced in the tortoise. In this species A-granules are polymorphic, too. Both types of granules show wide variations in size, which are particularly great in the tortoise. This species also exhibits the largest average sizes for A-granules (285 nm), and NA-granules (354 nm). The corresponding parameters for Lacerta and Natrix, are 255 and 179 nm for A- and 323 and 304 nm for NA-granules, respectively. The rough ER in A-cells of the tortoise regularly occurs in the form of circular dilations ('ergastosomes', Kanerva and Hervonen, 1973). Mitochondria sometimes contain longitudinal cristae with a crystalloid internal pattern. Large dense bodies which incorporate granules are abundant in NA-cells. Smaller dense bodies containing a few dense patches and membranes are present in both A- and NA-cells. Intermediate stages between dense bodies and what appear to be A- or NA-granules (if the latter have lost some of their amine-content) are frequently observed."} {"id": "PMID:1260843", "title": "Effects of heterologous cross-suture between the postganglionic sympathetic and the preganglionic parasympathetic nerve trunks of submandibular glands in cats.", "content": "After sectioning the postganglionic adrenergic sympathetic nerve trunk for the submandibular gland, as close to the submandibular artery as practicable, its central end was sutured to the peripheral end of the preganglionic cholinergic parasympathetic nerve trunk for the gland, the chorda, which had been sectioned where it left the lingual nerve. The effects of this heterologous cross-sature were studied at different times, up to 1 year afterwards, by assessing the physiological and pharmacological responses of the glands and the neuro-histochemical changes in the nerve trunks and in the nerves within the glands. In all cases adrenergic sympathetic nerves grew across the site of suture and down the erstwhile cholinergic parasympathetic trunk, eventually to develop connections in the gland. In some cases the functional adrenergic reinnervation of the submandibular gland appeared to result exclusively or predominantly from the direct downgrowth of adrenergic axons to the gland, via the crossed nerves. In other cases however, in addition to a direct glandular reinnervation, there was some physiological and morphological evidence which suggested that possible heterogneous synaptic contracts may have been created between postganglionic sympathetic axons and cholinergic ganglion cells in the chorda nerve.", "contents": "Effects of heterologous cross-suture between the postganglionic sympathetic and the preganglionic parasympathetic nerve trunks of submandibular glands in cats. After sectioning the postganglionic adrenergic sympathetic nerve trunk for the submandibular gland, as close to the submandibular artery as practicable, its central end was sutured to the peripheral end of the preganglionic cholinergic parasympathetic nerve trunk for the gland, the chorda, which had been sectioned where it left the lingual nerve. The effects of this heterologous cross-sature were studied at different times, up to 1 year afterwards, by assessing the physiological and pharmacological responses of the glands and the neuro-histochemical changes in the nerve trunks and in the nerves within the glands. In all cases adrenergic sympathetic nerves grew across the site of suture and down the erstwhile cholinergic parasympathetic trunk, eventually to develop connections in the gland. In some cases the functional adrenergic reinnervation of the submandibular gland appeared to result exclusively or predominantly from the direct downgrowth of adrenergic axons to the gland, via the crossed nerves. In other cases however, in addition to a direct glandular reinnervation, there was some physiological and morphological evidence which suggested that possible heterogneous synaptic contracts may have been created between postganglionic sympathetic axons and cholinergic ganglion cells in the chorda nerve."} {"id": "PMID:1260844", "title": "The cells that secrete the beaks in octopods and squids (Mollusca, Cephalopoda).", "content": "A single layer of cell secrets the hard cephalopod beaks. The beccublasts are tall columnar cells that separate the beak from the surrounding buccal muscles, and must serve to attach these muscles to the beak. Within the cell layer there are three types of cells. The first, and most frequently found contain cell-long fibrils. These fibrils may have contractile and tensile properties. Complex trabeculae extend from the beccublasts into the matrix of the beak. The fibrils are attached to these trabeculae and at the other end of the cells they are anchored near to the beccublast-muscle cell interface, closely associated with the muscles that move the beak. The second group of cells contain masses of endoplasmic reticulum the cysternae of which are arranged along the long axis of the cell. These cells also contain dense granules and are probably the major source of beak hard tissue. It is probable that each cell secretes its own column of beak hard tissue. The third group of cells cells contains a mixture of fibrils and secretory tissue. In the beccublast layer there are changes in the proportion of the three types of cells depending upon the region sampled. In the region where growth is most active there are mostly secretory cells, whereas near the biting and wearing tip there are mainly anchoring type cells.", "contents": "The cells that secrete the beaks in octopods and squids (Mollusca, Cephalopoda). A single layer of cell secrets the hard cephalopod beaks. The beccublasts are tall columnar cells that separate the beak from the surrounding buccal muscles, and must serve to attach these muscles to the beak. Within the cell layer there are three types of cells. The first, and most frequently found contain cell-long fibrils. These fibrils may have contractile and tensile properties. Complex trabeculae extend from the beccublasts into the matrix of the beak. The fibrils are attached to these trabeculae and at the other end of the cells they are anchored near to the beccublast-muscle cell interface, closely associated with the muscles that move the beak. The second group of cells contain masses of endoplasmic reticulum the cysternae of which are arranged along the long axis of the cell. These cells also contain dense granules and are probably the major source of beak hard tissue. It is probable that each cell secretes its own column of beak hard tissue. The third group of cells cells contains a mixture of fibrils and secretory tissue. In the beccublast layer there are changes in the proportion of the three types of cells depending upon the region sampled. In the region where growth is most active there are mostly secretory cells, whereas near the biting and wearing tip there are mainly anchoring type cells."} {"id": "PMID:1260845", "title": "The postnatal development of myelinated nerve fibres in the visual cortex of the cat: a stereological and electron microscopical investigation.", "content": "With the aid of stereological procedures the development of myelinated nerve fibres (MF) was quantitatively investigated in electron micrographs of the visual cortex from animals of different ages: 36 days-old, the age at which fibres first appear, through adulthood. A short description of tissue treatment, methods and qualitative results is given. The following quantitative results are presented: 1. Myelinization begins at about the 36th day postpartum and is not completed by the 164th day. At this time a lack of about 20% MF can be observed. 2. The average diameter of MF decreases from 1.3 mum to 0.8 mum from day 36 to adulthood. 3. The first MF appear near the border of the album. 4. Beginning with the 55th day, small MF arise in layer I, showing two periods of growth. 5. The maximum MF density in the region of layer IV corresponds to the strip of Baillarger. Other aspects of visual cortex development are dealt with in the Discussion. The following conclusions can be drawn: a) The growing of in- and output-MF is completed first. b) The development of the internal connecting systems in layers I and IV begins a little later and is completed by the 5th month. c) The MF in layers II and III appear after the 4th month. Kaes (1907) has also described a continuation of MF growth in man lasting into the twenties.", "contents": "The postnatal development of myelinated nerve fibres in the visual cortex of the cat: a stereological and electron microscopical investigation. With the aid of stereological procedures the development of myelinated nerve fibres (MF) was quantitatively investigated in electron micrographs of the visual cortex from animals of different ages: 36 days-old, the age at which fibres first appear, through adulthood. A short description of tissue treatment, methods and qualitative results is given. The following quantitative results are presented: 1. Myelinization begins at about the 36th day postpartum and is not completed by the 164th day. At this time a lack of about 20% MF can be observed. 2. The average diameter of MF decreases from 1.3 mum to 0.8 mum from day 36 to adulthood. 3. The first MF appear near the border of the album. 4. Beginning with the 55th day, small MF arise in layer I, showing two periods of growth. 5. The maximum MF density in the region of layer IV corresponds to the strip of Baillarger. Other aspects of visual cortex development are dealt with in the Discussion. The following conclusions can be drawn: a) The growing of in- and output-MF is completed first. b) The development of the internal connecting systems in layers I and IV begins a little later and is completed by the 5th month. c) The MF in layers II and III appear after the 4th month. Kaes (1907) has also described a continuation of MF growth in man lasting into the twenties."} {"id": "PMID:1260848", "title": "Percutaneous catheter emboli: sources and prevention.", "content": "Percutaneous coronary arteriography has been associated with numerous reports of embolic complications. Efforts to minimize such complications have focused upon normal hemostatic functions and the possible preventative role of systemic heparin. In considering the source and prevention of catheter emboli it is useful to review the mechanisms by which particulate matter may be introduced into the aortic root and to recognize that foreign material unaffected by anticoagulation may constitute a significant source of emboli. A simple technical protocol described in this communication has been followed during 3,500 percutaneous transfemoral coronary arteriograms using the Judkins approach. During this experience no embolic complications have been observed.", "contents": "Percutaneous catheter emboli: sources and prevention. Percutaneous coronary arteriography has been associated with numerous reports of embolic complications. Efforts to minimize such complications have focused upon normal hemostatic functions and the possible preventative role of systemic heparin. In considering the source and prevention of catheter emboli it is useful to review the mechanisms by which particulate matter may be introduced into the aortic root and to recognize that foreign material unaffected by anticoagulation may constitute a significant source of emboli. A simple technical protocol described in this communication has been followed during 3,500 percutaneous transfemoral coronary arteriograms using the Judkins approach. During this experience no embolic complications have been observed."} {"id": "PMID:1260849", "title": "Treadmill exercise testing of mass screening for coronary risk factors.", "content": "The prevalence of an abnormal maximal treadmill stress test (MTST) was correlated with coronary risk factors in 1,077 asymptomatic adults (709 men and 368 women) in Long Beach, California. Of 1,077 adults, 113 (10.5%) had a positive MTST. A positive MTST was correlated with sex (p less than 0.001), age (p less than 0.001), a serum cholesterol less than or equal to 200 mg% (p less than 0.02), hypertriglyceridemia (p less than 0.05), cigarette smoking (p less than 0.025), and with the number of coronary risk factors (p less than 0.005) but not with hypertension, cigar or pipe smoking, obesity, or blood sugar.", "contents": "Treadmill exercise testing of mass screening for coronary risk factors. The prevalence of an abnormal maximal treadmill stress test (MTST) was correlated with coronary risk factors in 1,077 asymptomatic adults (709 men and 368 women) in Long Beach, California. Of 1,077 adults, 113 (10.5%) had a positive MTST. A positive MTST was correlated with sex (p less than 0.001), age (p less than 0.001), a serum cholesterol less than or equal to 200 mg% (p less than 0.02), hypertriglyceridemia (p less than 0.05), cigarette smoking (p less than 0.025), and with the number of coronary risk factors (p less than 0.005) but not with hypertension, cigar or pipe smoking, obesity, or blood sugar."} {"id": "PMID:1260850", "title": "Effects of intravenous glucose during pacing-induced angina pectoris in patients with coronary artery disease.", "content": "The effects of hypertonic glucose infusion on the anginal threshold determined by atrial pacing was studied in 14 patients with significant coronary artery disease. After glucose, angina occurred at a significantly lower heart rate and double product (systolic arterial pressure x heart rate), suggesting a decreased tolerance to ischemic stress. No stoichiometric relationship was noted between glucose uptake and lactate production, and there was no evidence that hypertonic glucose infusion resulted in enhanced anaerobic glycolysis in the ischemic myocardium. Acute elevation of plasma glucose levels may not be beneficial to patients with coronary artery disease.", "contents": "Effects of intravenous glucose during pacing-induced angina pectoris in patients with coronary artery disease. The effects of hypertonic glucose infusion on the anginal threshold determined by atrial pacing was studied in 14 patients with significant coronary artery disease. After glucose, angina occurred at a significantly lower heart rate and double product (systolic arterial pressure x heart rate), suggesting a decreased tolerance to ischemic stress. No stoichiometric relationship was noted between glucose uptake and lactate production, and there was no evidence that hypertonic glucose infusion resulted in enhanced anaerobic glycolysis in the ischemic myocardium. Acute elevation of plasma glucose levels may not be beneficial to patients with coronary artery disease."} {"id": "PMID:1260851", "title": "Angiographic assessment of right ventricular volumes and ejection fraction.", "content": "Since the advent of cardiovascular angiography only a few decades ago (1), a massive number of data related to the ventricular function have been accumulated. Specifically, left ventricular (LV) geometry, volumes, and patterns of contractility have been extensively investigated (2-7), especially in patients with coronary artery disease (8-11). In contrast, much less attention has been given to the characteristics of the right ventricle (RV). This has been due partially to the fact that the LV was always considered to be more important chamber of the heart. The relative neglect of RV performance has been further compounded by difficulties in analyzing the geometry of the RV chamber: while the LV configuration approximately resembles an ellipsoid of revolution (and therefore lends itself to relatively simple mathematical analysis), the RV has always been considered a somewhat amorphous structure that does not yield to simple geometric manipulation. In this review, recent approaches to the angiographic measurements of RV volumes and ejection fraction are examined.", "contents": "Angiographic assessment of right ventricular volumes and ejection fraction. Since the advent of cardiovascular angiography only a few decades ago (1), a massive number of data related to the ventricular function have been accumulated. Specifically, left ventricular (LV) geometry, volumes, and patterns of contractility have been extensively investigated (2-7), especially in patients with coronary artery disease (8-11). In contrast, much less attention has been given to the characteristics of the right ventricle (RV). This has been due partially to the fact that the LV was always considered to be more important chamber of the heart. The relative neglect of RV performance has been further compounded by difficulties in analyzing the geometry of the RV chamber: while the LV configuration approximately resembles an ellipsoid of revolution (and therefore lends itself to relatively simple mathematical analysis), the RV has always been considered a somewhat amorphous structure that does not yield to simple geometric manipulation. In this review, recent approaches to the angiographic measurements of RV volumes and ejection fraction are examined."} {"id": "PMID:1260852", "title": "Evaluation of left ventricular performance in coronary heart disease: use of isometric handgrip stress test.", "content": "The usefulness of isometric handgrip exercise in the assessment of left ventricular function was studied in 27 patients, all of whom had angiographically documented coronary artery disease. The effect of extensiveness of coronary disease and presence or absence of collaterals (both delineated by coronary arteriography) on the response to handgrip stress was also evaluated. Of 11 patients with a normal handgrip response, 4 exhibited a normal left ventriculogram and 7 were abnormal. Of these 7, 6 had inferior hypokinesis. Conversely, of 16 patients with an abnormal response to handgrip, 15 had abnormal ventriculograms. Of these, 9 had anterior akinesis. Of patients with a normal handgrip response 82% had two- or three-vessel coronary disease, and 94% with an abnormal response exhibited two- or three-vessel obstruction. There was no observed correlation between the presence or absence of collaterals and the response to handgrip. This study indicates that (1) handgrip stress, when combined with left ventriculography, often yields important additional information regarding the effect of localized contraction abnormalities on overall left ventricular performance; (2) the extent of coronary obstructive disease or the presence of collaterals per se do not appear to be the primary determinants of left ventricular performance; (3) it is possible that the location as well as severity and extent of left ventricular contraction abnormality may play an important role in determining overall left ventricular performance.", "contents": "Evaluation of left ventricular performance in coronary heart disease: use of isometric handgrip stress test. The usefulness of isometric handgrip exercise in the assessment of left ventricular function was studied in 27 patients, all of whom had angiographically documented coronary artery disease. The effect of extensiveness of coronary disease and presence or absence of collaterals (both delineated by coronary arteriography) on the response to handgrip stress was also evaluated. Of 11 patients with a normal handgrip response, 4 exhibited a normal left ventriculogram and 7 were abnormal. Of these 7, 6 had inferior hypokinesis. Conversely, of 16 patients with an abnormal response to handgrip, 15 had abnormal ventriculograms. Of these, 9 had anterior akinesis. Of patients with a normal handgrip response 82% had two- or three-vessel coronary disease, and 94% with an abnormal response exhibited two- or three-vessel obstruction. There was no observed correlation between the presence or absence of collaterals and the response to handgrip. This study indicates that (1) handgrip stress, when combined with left ventriculography, often yields important additional information regarding the effect of localized contraction abnormalities on overall left ventricular performance; (2) the extent of coronary obstructive disease or the presence of collaterals per se do not appear to be the primary determinants of left ventricular performance; (3) it is possible that the location as well as severity and extent of left ventricular contraction abnormality may play an important role in determining overall left ventricular performance."} {"id": "PMID:1260853", "title": "Echocardiographic criteria of normal left atrial size in adults.", "content": "Although the measurement of left atrial diameter (LAD) is a standard part of any echocardiographic examination, the normal range for adults has never been well established or correlated with body surface area (BSA) and sex. We studied 100 males and 100 females whose ages ranged from 15 to 70 years, with no evidence of mitral value disease or other form of heart disease which might cause left atrial enlargement. All measurements were obtained between the external surface of posterior aortic root (AR) and the internal surface of the left atrial wall and were recorded at ventricular end diastole (ED) as well as end systole (ES). The LAD at ED ranged from 9.5 to 29.5 mm with a mean of 19 mm +/- 5.0 S.D.; the diameter at ES ranged from 18.3 mm to 38.7 mm with a mean of 28.5 mm +/- 5.1 S.D. The mean LAD at ED was 20.7 mm +/- 4.8 S.D. in makes compared to the mean diameter of 18.3 +/- 4.9 S.D. in females which represents a significant difference (p less than 0.001). The LAD did not correlate with BSA. The left atrial dimension by ultrasound in these 200 normal patients was compared with the same measurement in 50 catheterized patients with mitral valve disease and proven left atrial enlargement. When absolute values of the left atrial dimension both at end systole and end diastole were determined by ultrasound, there was a clear separation between normal and abnormal (p less than 0.001).", "contents": "Echocardiographic criteria of normal left atrial size in adults. Although the measurement of left atrial diameter (LAD) is a standard part of any echocardiographic examination, the normal range for adults has never been well established or correlated with body surface area (BSA) and sex. We studied 100 males and 100 females whose ages ranged from 15 to 70 years, with no evidence of mitral value disease or other form of heart disease which might cause left atrial enlargement. All measurements were obtained between the external surface of posterior aortic root (AR) and the internal surface of the left atrial wall and were recorded at ventricular end diastole (ED) as well as end systole (ES). The LAD at ED ranged from 9.5 to 29.5 mm with a mean of 19 mm +/- 5.0 S.D.; the diameter at ES ranged from 18.3 mm to 38.7 mm with a mean of 28.5 mm +/- 5.1 S.D. The mean LAD at ED was 20.7 mm +/- 4.8 S.D. in makes compared to the mean diameter of 18.3 +/- 4.9 S.D. in females which represents a significant difference (p less than 0.001). The LAD did not correlate with BSA. The left atrial dimension by ultrasound in these 200 normal patients was compared with the same measurement in 50 catheterized patients with mitral valve disease and proven left atrial enlargement. When absolute values of the left atrial dimension both at end systole and end diastole were determined by ultrasound, there was a clear separation between normal and abnormal (p less than 0.001)."} {"id": "PMID:1260854", "title": "Prolapsing mitral valve leaflet syndrome. A spectrum that includes cleft posterior mitral valve.", "content": "Two patients with a prolapse and cleft posterior mitral leaflet were studied. The first case had an associated ostium secundum type atrial septal defect. In both cases, the pansystolic regurgitation of contrast material during angiography corresponded to the pansystolic configuration of the murmur. In each instance, the systolic murmurs displayed a late systolic accentuation during the maximal prolapse of the mitral valve. The echocardiographic studies demonstrated only a late systolic prolapse which in both patients corresponded angiocardiographically to the maximum buckling of the pansystolic prolapse. Echocardiographic and angiocardiographic features of cleft posterior mitral valve leaflet are discussed.", "contents": "Prolapsing mitral valve leaflet syndrome. A spectrum that includes cleft posterior mitral valve. Two patients with a prolapse and cleft posterior mitral leaflet were studied. The first case had an associated ostium secundum type atrial septal defect. In both cases, the pansystolic regurgitation of contrast material during angiography corresponded to the pansystolic configuration of the murmur. In each instance, the systolic murmurs displayed a late systolic accentuation during the maximal prolapse of the mitral valve. The echocardiographic studies demonstrated only a late systolic prolapse which in both patients corresponded angiocardiographically to the maximum buckling of the pansystolic prolapse. Echocardiographic and angiocardiographic features of cleft posterior mitral valve leaflet are discussed."} {"id": "PMID:1260855", "title": "Echocardiographic findings in a patient with primary pulmonary hypertension.", "content": "This is a report of the echocardiographic findings in a 9-year-old white female with primary pulmonary arterial hypertension confirmed by catheterization and later at autopsy. The reported findings of an absent \"a\" wave, a flat diastolic E to F slope, and a midsystolic closure of the pulmonic valve were observed. In addition, tricuspid valve prolapse was noted. Prolapse of the tricuspid valve may be part of the mechanism of tricuspid insufficiency in a patient with pulmonary hypertension.", "contents": "Echocardiographic findings in a patient with primary pulmonary hypertension. This is a report of the echocardiographic findings in a 9-year-old white female with primary pulmonary arterial hypertension confirmed by catheterization and later at autopsy. The reported findings of an absent \"a\" wave, a flat diastolic E to F slope, and a midsystolic closure of the pulmonic valve were observed. In addition, tricuspid valve prolapse was noted. Prolapse of the tricuspid valve may be part of the mechanism of tricuspid insufficiency in a patient with pulmonary hypertension."} {"id": "PMID:1260856", "title": "Aneurysm of the subclavian artery: a complication of retrograde brachial artery catheterization.", "content": "A case of an aneurysm of an anomalous right subclavian artery following retrograde catheterization of the right brachial artery is described. This complication was not recognized until the patient presented with symptoms related to a superior mediastinal mass. After appropriate studies were performed operative intervention was successful in establishing a patent subclavian artery.", "contents": "Aneurysm of the subclavian artery: a complication of retrograde brachial artery catheterization. A case of an aneurysm of an anomalous right subclavian artery following retrograde catheterization of the right brachial artery is described. This complication was not recognized until the patient presented with symptoms related to a superior mediastinal mass. After appropriate studies were performed operative intervention was successful in establishing a patent subclavian artery."} {"id": "PMID:1260857", "title": "The hemodynamic simulation of mitral regurgitation in ventricular septal defect after myocardial infarction.", "content": "The development of a ventricular septal defect (VSD) following myocardial infarction is an uncommon complication which clinically can be confused with mitral insufficiency due to infarction of a papillary muscle. The clinical and hemodynamic records of six patients with documented acute VSD secondary to myocardial infarction were analyzed to determine which descriptors would be of value in clinically separating these two entities. All six of our patients had a right heart catheterization showing an oxygen step-up consistent with a VSD, and five had a large pulmonary wedge V wave suggesting concomitant mitral insufficiency. The echocardiogram showed only nonspecific chamber enlargement. Since these patients were being considered for open heart surgery to close the VSD, left and right cardiac catheterization including selective coronary arteriography was done. Despite large V waves being present in the pulmonary wedge and/or left atrial pressure tracing in five of the six patients, no mitral insufficiency was present on the left ventricular cineangiograms. It is concluded that a large pulmonary wedge and/or left atrial V wave does not necessarily indicate mitral insufficiency. Since both a VSD and mitral insufficiency are surgically correctable, patients who develop new holosystolic murmurs following myocardial infarction should have complete right and left heart catheterizations with LV angiography for accurate diagnosis if surgical correction of the lesion is contemplated.", "contents": "The hemodynamic simulation of mitral regurgitation in ventricular septal defect after myocardial infarction. The development of a ventricular septal defect (VSD) following myocardial infarction is an uncommon complication which clinically can be confused with mitral insufficiency due to infarction of a papillary muscle. The clinical and hemodynamic records of six patients with documented acute VSD secondary to myocardial infarction were analyzed to determine which descriptors would be of value in clinically separating these two entities. All six of our patients had a right heart catheterization showing an oxygen step-up consistent with a VSD, and five had a large pulmonary wedge V wave suggesting concomitant mitral insufficiency. The echocardiogram showed only nonspecific chamber enlargement. Since these patients were being considered for open heart surgery to close the VSD, left and right cardiac catheterization including selective coronary arteriography was done. Despite large V waves being present in the pulmonary wedge and/or left atrial pressure tracing in five of the six patients, no mitral insufficiency was present on the left ventricular cineangiograms. It is concluded that a large pulmonary wedge and/or left atrial V wave does not necessarily indicate mitral insufficiency. Since both a VSD and mitral insufficiency are surgically correctable, patients who develop new holosystolic murmurs following myocardial infarction should have complete right and left heart catheterizations with LV angiography for accurate diagnosis if surgical correction of the lesion is contemplated."} {"id": "PMID:1260858", "title": "Template restriction in human chromatin.", "content": "DNA-dependent RNA polymerase from Escherchia coli was used to transcribe chromatin from human leukocytes and purified human DNA. RNA was labeled at the 5' terminus with either [gamma-32P]ATP or [gamma-32P]GTP and internally with [3H]UTP. Determination of the average chain length of the RNA molecules by the ratio of moles of 3H-labeled nucleotide incorporated to moles 32P-labeled nucleotide incorporated showed that the size of the transcript of purified DNA was about 2 1/2 times greater than those from chromatin. The percentage of chains initiated with ATP and GTP was observed to vary with the template, the ATP to GTP ratio being greater on chromatin. The kinetics of 3H and 32P hybridization of transcripts of purified DNA showed hybridization primarily to nonrepetitive sequences. Transcripts from the chromatin templates when hybridized to DNA showed a larger proportion of RNase resistance of the 32P-termini at low Cot's.", "contents": "Template restriction in human chromatin. DNA-dependent RNA polymerase from Escherchia coli was used to transcribe chromatin from human leukocytes and purified human DNA. RNA was labeled at the 5' terminus with either [gamma-32P]ATP or [gamma-32P]GTP and internally with [3H]UTP. Determination of the average chain length of the RNA molecules by the ratio of moles of 3H-labeled nucleotide incorporated to moles 32P-labeled nucleotide incorporated showed that the size of the transcript of purified DNA was about 2 1/2 times greater than those from chromatin. The percentage of chains initiated with ATP and GTP was observed to vary with the template, the ATP to GTP ratio being greater on chromatin. The kinetics of 3H and 32P hybridization of transcripts of purified DNA showed hybridization primarily to nonrepetitive sequences. Transcripts from the chromatin templates when hybridized to DNA showed a larger proportion of RNase resistance of the 32P-termini at low Cot's."} {"id": "PMID:1260859", "title": "Action of the head activator as a growth hormone in hydra.", "content": "At the cellular level the head activator from hydra acts as a mitogen or growth hormone. It shortens cell cycle times by stimulating cells arrested in the G2 period to go through mitosis. This is true for continuously proliferating cell types like epithelial cells, gland cells, and interstitial cells, and for differentiating interstitial cells including those undergoing a last mitosis before differentiating into nerves or nematocytes.", "contents": "Action of the head activator as a growth hormone in hydra. At the cellular level the head activator from hydra acts as a mitogen or growth hormone. It shortens cell cycle times by stimulating cells arrested in the G2 period to go through mitosis. This is true for continuously proliferating cell types like epithelial cells, gland cells, and interstitial cells, and for differentiating interstitial cells including those undergoing a last mitosis before differentiating into nerves or nematocytes."} {"id": "PMID:1260860", "title": "Action of the head activator on the determination of interstitial cells in hydra.", "content": "In addition to its role as a growth hormone (preceding paper), at the cellular level the head activator functions as one of the substances which control the determination of uncommitted stem cells in hydra. In the presence of head activator the determination of interstitial stem cells to nerve cells is stimulated, the determination of interstitial cells to nematocytes is inhibited. The determination of interstitial cells to nerves occurs shortly before or in the very early S period of interstitial cells.", "contents": "Action of the head activator on the determination of interstitial cells in hydra. In addition to its role as a growth hormone (preceding paper), at the cellular level the head activator functions as one of the substances which control the determination of uncommitted stem cells in hydra. In the presence of head activator the determination of interstitial stem cells to nerve cells is stimulated, the determination of interstitial cells to nematocytes is inhibited. The determination of interstitial cells to nerves occurs shortly before or in the very early S period of interstitial cells."} {"id": "PMID:1260861", "title": "Differentiation associated changes in thymidylate synthetase and thymidine kinase activities in intestinal cells.", "content": "Proliferative and mature intestinal cells of the jejunum and colon of rat, colon of man, and the surface cells of neoplastic colon lesions of man were assayed for thymidylate synthetase and thymidine kinase activities. Cells from the proliferative region of rat jejunal mucosa were found to have higher enzyme activities than cells from the non-proliferative region. Thymidylate synthetase activity was observed to decrease as cells migrated from base to upper crypt, whereas thymidine kinase activity increased during crypt migration and then declined as cells migrated onto villi. Thymidine kinase activity also remained elevated longer than thymidylate synthetase during cell migration in colonic mucosa of rat and man. High thymidine kinase: thymidylate synthetase ratios similar to those observed in flat mucosa before cells become fully mature were found in cells removed from expanding neoplastic lesions of man.", "contents": "Differentiation associated changes in thymidylate synthetase and thymidine kinase activities in intestinal cells. Proliferative and mature intestinal cells of the jejunum and colon of rat, colon of man, and the surface cells of neoplastic colon lesions of man were assayed for thymidylate synthetase and thymidine kinase activities. Cells from the proliferative region of rat jejunal mucosa were found to have higher enzyme activities than cells from the non-proliferative region. Thymidylate synthetase activity was observed to decrease as cells migrated from base to upper crypt, whereas thymidine kinase activity increased during crypt migration and then declined as cells migrated onto villi. Thymidine kinase activity also remained elevated longer than thymidylate synthetase during cell migration in colonic mucosa of rat and man. High thymidine kinase: thymidylate synthetase ratios similar to those observed in flat mucosa before cells become fully mature were found in cells removed from expanding neoplastic lesions of man."} {"id": "PMID:1260862", "title": "Phosphorylation of nonhistone chromosomal proteins early during the prereplicative phase of the cell cycle of WI-38 human diploid fibroblasts.", "content": "Stimulation of confluent monolayers of nondividing WI-38 cells to proliferate is accompanied by a doubling in the rate of phosphorylation of nonhistone chromosomal proteins during the first hour. The use of cycloheximide to inhibit protein synthesis does not appear to affect phosphorylation of the nonhistones. Nondividing and serum-stimulated cells exhibit qualitative differences in the phosphorylation and dephosphorylation of individual polypeptide peaks resolved by polyacrylamide gel electrophoresis. These results are consistent with other evidence implicating nonhistone protein phosphorylation as an early event involved in the activation of transcription occurring during cell proliferation.", "contents": "Phosphorylation of nonhistone chromosomal proteins early during the prereplicative phase of the cell cycle of WI-38 human diploid fibroblasts. Stimulation of confluent monolayers of nondividing WI-38 cells to proliferate is accompanied by a doubling in the rate of phosphorylation of nonhistone chromosomal proteins during the first hour. The use of cycloheximide to inhibit protein synthesis does not appear to affect phosphorylation of the nonhistones. Nondividing and serum-stimulated cells exhibit qualitative differences in the phosphorylation and dephosphorylation of individual polypeptide peaks resolved by polyacrylamide gel electrophoresis. These results are consistent with other evidence implicating nonhistone protein phosphorylation as an early event involved in the activation of transcription occurring during cell proliferation."} {"id": "PMID:1260943", "title": "Distribution of intercalative dye binding sites in chromatin.", "content": "Actinomycin D (AMD) and ethidium bromide (EB) were found to bind to chromatin isolated from a variety of gander tissues according to a strong and weak process analogous to that found for deproteinized DNA. Distribution of the dye intercalation sites in chromatin and DNA were evaluated at low r-values (dye bound per nucleotide) by following the appearance of free dye released from chromatin and DNA during thermal denaturation. The AMD dissociation profiles closely resembled the DNA or chromatin-DNA denaturation profiles; whereas the EB derivative dissociation profiles, indicated 3 major transitions for transcriptionally active chromatin with the main component corresponding to the single component which characterizes DNA. The DNA-like component was greatly reduced for mature erythrocyte chromatin but could be generated by removal of histone I and V. Removal of residual non acid-soluble proteins from dehistonized chromatin, urea treatment or dissociation and reconstitution of chromatin favoured conversion to the DNA-like component with loss of the other two. This study indicates that more than one type of binding exists generally in chromatin.", "contents": "Distribution of intercalative dye binding sites in chromatin. Actinomycin D (AMD) and ethidium bromide (EB) were found to bind to chromatin isolated from a variety of gander tissues according to a strong and weak process analogous to that found for deproteinized DNA. Distribution of the dye intercalation sites in chromatin and DNA were evaluated at low r-values (dye bound per nucleotide) by following the appearance of free dye released from chromatin and DNA during thermal denaturation. The AMD dissociation profiles closely resembled the DNA or chromatin-DNA denaturation profiles; whereas the EB derivative dissociation profiles, indicated 3 major transitions for transcriptionally active chromatin with the main component corresponding to the single component which characterizes DNA. The DNA-like component was greatly reduced for mature erythrocyte chromatin but could be generated by removal of histone I and V. Removal of residual non acid-soluble proteins from dehistonized chromatin, urea treatment or dissociation and reconstitution of chromatin favoured conversion to the DNA-like component with loss of the other two. This study indicates that more than one type of binding exists generally in chromatin."} {"id": "PMID:1260944", "title": "Protein modifications by activated carcinogens. II. The acetylation of ribonuclease by N-acetoxy-3-fluorenylacetamide.", "content": "The reaction of N-[3H]acetoxy-3-fluorenylacetamide (N-[3H]acetoxy-3-FAA), a potent carcinogen for the rat, with RNAase yielded three modified proteins separable from RNAase by ion exchange chromatography on Bio-Gel CM-30 with a gradient of increasing sodium ion concentration. Only minor amounts of RNAase were recovered. The modified proteins were labeled with 3H to a varying degree, and their order of elution was inversely related to the extent of labeling. The modification of the proteins was the result of the transfer of the acetyl group from N-[3H]acetoxy-3-FAA to RNAase. The evidence for this conclusion was (a) the release of 84-86% of the radioactivity as [3H] acetic acid from the two major proteins upon acid hydrolysis and (b) the isolation of eplision-N-[3H] acetyl-L-lysine from enzymatic hydrolysates of these proteins. A comparison of the present data with those previously reported for the acetylaton of RNAase by the isomeric carcinogen, N-acetoxy-2-FAA, showed that N-acetoxy-3-FAA is the more potent acetyl-lating agent. The present study in conjunction with the previous results, suggests that structural alteration of cellular nucleopholes by acylation may be a biochemical mechanism underlying the biological activity of N-acetoxy-3-FAA and related activated carcinogens.", "contents": "Protein modifications by activated carcinogens. II. The acetylation of ribonuclease by N-acetoxy-3-fluorenylacetamide. The reaction of N-[3H]acetoxy-3-fluorenylacetamide (N-[3H]acetoxy-3-FAA), a potent carcinogen for the rat, with RNAase yielded three modified proteins separable from RNAase by ion exchange chromatography on Bio-Gel CM-30 with a gradient of increasing sodium ion concentration. Only minor amounts of RNAase were recovered. The modified proteins were labeled with 3H to a varying degree, and their order of elution was inversely related to the extent of labeling. The modification of the proteins was the result of the transfer of the acetyl group from N-[3H]acetoxy-3-FAA to RNAase. The evidence for this conclusion was (a) the release of 84-86% of the radioactivity as [3H] acetic acid from the two major proteins upon acid hydrolysis and (b) the isolation of eplision-N-[3H] acetyl-L-lysine from enzymatic hydrolysates of these proteins. A comparison of the present data with those previously reported for the acetylaton of RNAase by the isomeric carcinogen, N-acetoxy-2-FAA, showed that N-acetoxy-3-FAA is the more potent acetyl-lating agent. The present study in conjunction with the previous results, suggests that structural alteration of cellular nucleopholes by acylation may be a biochemical mechanism underlying the biological activity of N-acetoxy-3-FAA and related activated carcinogens."} {"id": "PMID:1260945", "title": "The conversion of benzo(alpha)pyrene 4,5-oxide into 4-hydroxybenzo(alpha)pyrene in the presence of polyriboguanylic acid.", "content": "Incubation of benzo[alpha] pyrene 4,5-oxide with poly(G) in neutral aqueous ethanol resulted in the formation of covalent adducts and in the production of free 4-hydroxybenzo[alpha]pyrene. This phenol, which was identified by its UV spectral properties and by its chromatographic characteristics, was also formed but at a much slower rate when the epoxide was incubated with DNA or with GMP. Phenol formation was not detected when benzo[alpha]-pyrene 4,5-oxide was incubated for prolonged periods in the presence of poly(A), poly(C) or poly(U) or in the absence of nucleic acid. Formation of 4-hydroxybenzo[alpha] pyrene from the epoxide in the presence of poly(G) was not accompanied by detectable base modifications or by breakage of phosphodiester linkages.", "contents": "The conversion of benzo(alpha)pyrene 4,5-oxide into 4-hydroxybenzo(alpha)pyrene in the presence of polyriboguanylic acid. Incubation of benzo[alpha] pyrene 4,5-oxide with poly(G) in neutral aqueous ethanol resulted in the formation of covalent adducts and in the production of free 4-hydroxybenzo[alpha]pyrene. This phenol, which was identified by its UV spectral properties and by its chromatographic characteristics, was also formed but at a much slower rate when the epoxide was incubated with DNA or with GMP. Phenol formation was not detected when benzo[alpha]-pyrene 4,5-oxide was incubated for prolonged periods in the presence of poly(A), poly(C) or poly(U) or in the absence of nucleic acid. Formation of 4-hydroxybenzo[alpha] pyrene from the epoxide in the presence of poly(G) was not accompanied by detectable base modifications or by breakage of phosphodiester linkages."} {"id": "PMID:1260946", "title": "Effect of 7,8-benzolfavone on the formation of benzo(alpha)pyrene-DNA-bound products in hamster embryo cells.", "content": "The hydrocarbon-deoxyribonucleoside products present in enzyme digests of DNA from hamster embryo cultures that had been treated with[3H]-benzo[alpha]pyrene (BP) were isolated by chromatography on Sephadex LH20 columns. The products isolated from cells treated with 7,8-benzoflavone (7,8-BF) for 18 h prior to the addition of [3H] BP were indistinguishable from the products isolated from untreated cultures, but the amounts of these products decreased with increasing concentrations of 7,8-BF. The amount of BP metabolized was also decreased in 7,8-BF-treated cultures. The decrease in the amounts of hydrocarbon-deoxyribonucleoside products per mg DNA was logarithmic with respect to the decrease in BP metabolism. The findings are consistent with the hypothesis that 7,8-BF inhibits both an initial and a later metabolic step involved in the conversion of BP to a reactive species that binds to cellular DNA.", "contents": "Effect of 7,8-benzolfavone on the formation of benzo(alpha)pyrene-DNA-bound products in hamster embryo cells. The hydrocarbon-deoxyribonucleoside products present in enzyme digests of DNA from hamster embryo cultures that had been treated with[3H]-benzo[alpha]pyrene (BP) were isolated by chromatography on Sephadex LH20 columns. The products isolated from cells treated with 7,8-benzoflavone (7,8-BF) for 18 h prior to the addition of [3H] BP were indistinguishable from the products isolated from untreated cultures, but the amounts of these products decreased with increasing concentrations of 7,8-BF. The amount of BP metabolized was also decreased in 7,8-BF-treated cultures. The decrease in the amounts of hydrocarbon-deoxyribonucleoside products per mg DNA was logarithmic with respect to the decrease in BP metabolism. The findings are consistent with the hypothesis that 7,8-BF inhibits both an initial and a later metabolic step involved in the conversion of BP to a reactive species that binds to cellular DNA."} {"id": "PMID:1260947", "title": "Attachment of ribosomes to endoplasmic membranes in mouse pancreas. Degranulation in vivo caused by the inducers of autophagocytosis neutral red, vinblastine, puromycin, and cadmium ions, and prevention by cycloheximide.", "content": "The present investigation was undertaken to discover whether in vivo inducers of autophagocytosis such as neutral red (0.40 mg/g body weight), cadmium chloride (0.15 mg/animal), vinblastine sulfate (7.5 mg/kg b.w.), and puromycin dihydrochloride (0.20 mg/g b.w.) are able to produce degranulation of rough surfaced endoplasmic reticulum (ER) of pancreatic acinar cells as we suggested earlier. Using a modified method of Blobel and Potter about 30% of the total ribosomes of untreated control pancreas were recovered in the free form, and 70% in the membrane-bound form. Cycloheximide (0.20 mg/g body weight) had no effect on this distribution of ribosomes, while neutral red, cadmium ions, vinblastine, and puromycin led to the presence of more free ribosomes: thus up to 70% of the total cytoplasmic ribosomes were recovered in the free form 30 to 60 min after treatments with the autophagic inducers. Pretreatments with cycloheximide prevented this shift and the distribution of ribosomes remained normal. On the basis of these and previous results we conclude that in pancreas an initial degranulation of the ER caused by these agents is a precondition of membrane transformation in autophagocytosis which is preventable by cycloheximide. Confirming the ultrastructural data of Longnecker et al. on rat pancreas, puromycin was shown to cause different forms of cellular injury including autophagocytosis. All forms of cellular injury were also prevented by pretreatment with cycloheximide in mouse pancreas.", "contents": "Attachment of ribosomes to endoplasmic membranes in mouse pancreas. Degranulation in vivo caused by the inducers of autophagocytosis neutral red, vinblastine, puromycin, and cadmium ions, and prevention by cycloheximide. The present investigation was undertaken to discover whether in vivo inducers of autophagocytosis such as neutral red (0.40 mg/g body weight), cadmium chloride (0.15 mg/animal), vinblastine sulfate (7.5 mg/kg b.w.), and puromycin dihydrochloride (0.20 mg/g b.w.) are able to produce degranulation of rough surfaced endoplasmic reticulum (ER) of pancreatic acinar cells as we suggested earlier. Using a modified method of Blobel and Potter about 30% of the total ribosomes of untreated control pancreas were recovered in the free form, and 70% in the membrane-bound form. Cycloheximide (0.20 mg/g body weight) had no effect on this distribution of ribosomes, while neutral red, cadmium ions, vinblastine, and puromycin led to the presence of more free ribosomes: thus up to 70% of the total cytoplasmic ribosomes were recovered in the free form 30 to 60 min after treatments with the autophagic inducers. Pretreatments with cycloheximide prevented this shift and the distribution of ribosomes remained normal. On the basis of these and previous results we conclude that in pancreas an initial degranulation of the ER caused by these agents is a precondition of membrane transformation in autophagocytosis which is preventable by cycloheximide. Confirming the ultrastructural data of Longnecker et al. on rat pancreas, puromycin was shown to cause different forms of cellular injury including autophagocytosis. All forms of cellular injury were also prevented by pretreatment with cycloheximide in mouse pancreas."} {"id": "PMID:1260949", "title": "Dimethylnitrosamine-demethylase: absence of increased enzyme catabolism and multiplicity of effector sites in repression. Hemoprotein involvement.", "content": "Evidence is presented that the previously observed decrease of the Vmax of hepatic microsomal demethylation of dimethylnitrosamine (DMN), following pretreatment of rats with 3-methylcholanthrene (MC), is not due to increase in the rate of breakdown but to decrease of de novo synthesis. Determinations of Vmax at time intervals in the transition from the high steady-state level induced by a carbohydrate-devoid casein diet, down to the low steady-state level of carbohydrate-containing basal diet, yielded two consecutive slopes; descent from the basal diet level to the lower steady-state level following pretreatment with MC yielded one slope. Plotting these slopes against the initial Vmax values gave a typical exponential curve (or straight line if the logs of slopes are used) indicating that the rate of enzyme decay in the MC-treated animals is not greater than that expected from normal enzyme catabolism. A multiplicity of effector sites appears to be involved in the repressor action of different structural types; for example, repression by MC (46.6%) and by phenobarbital (23.9%) in combination are approximately additive (62.0%), rather than competitive, indicating that the two agents act at different sites. A P-450 type cytochrome is involved in the demethylation of DMN. DMN-demethylase is inhibited by carbon monoxide, but the susceptibility to CO is far greater than that observed previously with 3,4-benzopyrene hydroxylation; inhibition of DMN-demethylase as a function of CO concentration follows typical enzyme kinetics. However, while both phenobarbital and MC powerfully repress the DMN-demethylase, we have confirmed that they are strong inducers of the synthesis of P-450 and P-448, respectively, as estimated from the difference spectra.", "contents": "Dimethylnitrosamine-demethylase: absence of increased enzyme catabolism and multiplicity of effector sites in repression. Hemoprotein involvement. Evidence is presented that the previously observed decrease of the Vmax of hepatic microsomal demethylation of dimethylnitrosamine (DMN), following pretreatment of rats with 3-methylcholanthrene (MC), is not due to increase in the rate of breakdown but to decrease of de novo synthesis. Determinations of Vmax at time intervals in the transition from the high steady-state level induced by a carbohydrate-devoid casein diet, down to the low steady-state level of carbohydrate-containing basal diet, yielded two consecutive slopes; descent from the basal diet level to the lower steady-state level following pretreatment with MC yielded one slope. Plotting these slopes against the initial Vmax values gave a typical exponential curve (or straight line if the logs of slopes are used) indicating that the rate of enzyme decay in the MC-treated animals is not greater than that expected from normal enzyme catabolism. A multiplicity of effector sites appears to be involved in the repressor action of different structural types; for example, repression by MC (46.6%) and by phenobarbital (23.9%) in combination are approximately additive (62.0%), rather than competitive, indicating that the two agents act at different sites. A P-450 type cytochrome is involved in the demethylation of DMN. DMN-demethylase is inhibited by carbon monoxide, but the susceptibility to CO is far greater than that observed previously with 3,4-benzopyrene hydroxylation; inhibition of DMN-demethylase as a function of CO concentration follows typical enzyme kinetics. However, while both phenobarbital and MC powerfully repress the DMN-demethylase, we have confirmed that they are strong inducers of the synthesis of P-450 and P-448, respectively, as estimated from the difference spectra."} {"id": "PMID:1260950", "title": "The kinetics of the alkaline hydrolysis of phosphotriesters in DNA.", "content": "The degradation in alkali of normal DNA and DNA alkylated with dimethyl sulphate (DMS), N-methyl-N-nitrosourea (MNUA) and N-ethyl-N-nitrosourea (ENUA) has been investigated using analytical ultracentrifugation techniques. For control T7-DNA (w.st. denatured form 12.5 - 10(6) daltons) the rate of degradation at 37 degrees varies from 0.14 breaks/molecule/h in 0.1 M NaOH to 1.2 breaks/molecule/h in 0.4 M NaOH. When DNA is alkylated with reagents known to produce phosphotriesters addition of alkali leads to an initial rapid degradation not observed with control DNA. Ethyl phosphotriesters are hydrolysed at about half the rate of methyl phosphotriesters. Approximately one third of the methyl or ethyl phosphotriesters present hydrolyse to give breaks in the DNA chain.", "contents": "The kinetics of the alkaline hydrolysis of phosphotriesters in DNA. The degradation in alkali of normal DNA and DNA alkylated with dimethyl sulphate (DMS), N-methyl-N-nitrosourea (MNUA) and N-ethyl-N-nitrosourea (ENUA) has been investigated using analytical ultracentrifugation techniques. For control T7-DNA (w.st. denatured form 12.5 - 10(6) daltons) the rate of degradation at 37 degrees varies from 0.14 breaks/molecule/h in 0.1 M NaOH to 1.2 breaks/molecule/h in 0.4 M NaOH. When DNA is alkylated with reagents known to produce phosphotriesters addition of alkali leads to an initial rapid degradation not observed with control DNA. Ethyl phosphotriesters are hydrolysed at about half the rate of methyl phosphotriesters. Approximately one third of the methyl or ethyl phosphotriesters present hydrolyse to give breaks in the DNA chain."} {"id": "PMID:1260951", "title": "The relationship between the turnover of UTP and RNA synthesis in cultured cells treated with aflatoxin B1.", "content": "Methods have been adapted to measure the specific activity of UTP in cells in monolayer culture. In HeLa cells labelled with [3H]uridine and treated with aflatoxin B1 there was reduced radioactivity in crude acid extracts, but the toxin did not affect the radioactive incorporation into UTP. Using cells in which the UTP was pre-labelled, the subsequent addition of aflatoxin B1 inhibited UTP incorporation into RNA. Accordingly aflatoxin B1 did not inhibit the uptake of uridine or the latter's conversion to UTP but inhibited the incorporation of UTP into RNA.", "contents": "The relationship between the turnover of UTP and RNA synthesis in cultured cells treated with aflatoxin B1. Methods have been adapted to measure the specific activity of UTP in cells in monolayer culture. In HeLa cells labelled with [3H]uridine and treated with aflatoxin B1 there was reduced radioactivity in crude acid extracts, but the toxin did not affect the radioactive incorporation into UTP. Using cells in which the UTP was pre-labelled, the subsequent addition of aflatoxin B1 inhibited UTP incorporation into RNA. Accordingly aflatoxin B1 did not inhibit the uptake of uridine or the latter's conversion to UTP but inhibited the incorporation of UTP into RNA."} {"id": "PMID:1260959", "title": "Branched long-chain bases from the bivalve Corbicula sandai.", "content": "Long-chain bases were liberated from a crude mixture of sphingolipids from whole tissue of the fresh-water bivalve C. sandai, and conversion of the bases into N-acetyl-0-trimethylsily derivatives was accomplished. The derivatized bases were analyzed by combined gas-liquid chromatography and mass spectrometry. A portion of the sphingolipids was subjected to catalytic hydrogenation from whch saturated long-chain bases (sphinganines) were obtained. The saturated bases were oxidized with lead tetra-acetate and the aldehydes produced were analyzed by gas-liquid chromatography. The aldehydes were further oxidized to acids with silver oxide, the resulting fatty acids methylated and also analyzed by gas-liquid chromatography. By these analyses, altogether five long-chain bases were identified, consisting of hexadeca-4-sphingenine (15%), heptadeca-4-sphingenine (2%), iso-octadeca-4-sphingenine (13%), octadeca-4-sphingenine (39%) and anteiso-noadeca-4-sphingenine (31%). So far no branches have been found in shellfish spingolipid long-chain bases.", "contents": "Branched long-chain bases from the bivalve Corbicula sandai. Long-chain bases were liberated from a crude mixture of sphingolipids from whole tissue of the fresh-water bivalve C. sandai, and conversion of the bases into N-acetyl-0-trimethylsily derivatives was accomplished. The derivatized bases were analyzed by combined gas-liquid chromatography and mass spectrometry. A portion of the sphingolipids was subjected to catalytic hydrogenation from whch saturated long-chain bases (sphinganines) were obtained. The saturated bases were oxidized with lead tetra-acetate and the aldehydes produced were analyzed by gas-liquid chromatography. The aldehydes were further oxidized to acids with silver oxide, the resulting fatty acids methylated and also analyzed by gas-liquid chromatography. By these analyses, altogether five long-chain bases were identified, consisting of hexadeca-4-sphingenine (15%), heptadeca-4-sphingenine (2%), iso-octadeca-4-sphingenine (13%), octadeca-4-sphingenine (39%) and anteiso-noadeca-4-sphingenine (31%). So far no branches have been found in shellfish spingolipid long-chain bases."} {"id": "PMID:1260960", "title": "Mass spectral fragmentation of 5alpha-hydroxysteroids.", "content": "The mass spectra of a number of C-4alpha- and C-4beta-alkylated cholestan-3beta, 5alpha-diols have been found to contain an intense ion at m/e 332. the corresponding 6beta-alkylated (R) cholestan-3beta, 5alpha-diols exhibit an abundant ion at m/e 331 + R. The mass spectra of cholestan-5alpha-ol and cholestan-3beta, 5alpha-diol also show an ion at m/e 332 which, however, is of relatively low abundance. The ion in question appears to arise from fragmentation processes which are characteristics of 5alpha-hydroxysteroids. A similar fragmentation has been found to occur in cases of C-4 and C-6beta-alkylated 5alpha-hysroxy-cholestan-3-ones. The results of isotopic labeling, high resolution and metastable ion defocusing studies are discussed in terms of the origin of several of the ions in the spectra of the various compounds.", "contents": "Mass spectral fragmentation of 5alpha-hydroxysteroids. The mass spectra of a number of C-4alpha- and C-4beta-alkylated cholestan-3beta, 5alpha-diols have been found to contain an intense ion at m/e 332. the corresponding 6beta-alkylated (R) cholestan-3beta, 5alpha-diols exhibit an abundant ion at m/e 331 + R. The mass spectra of cholestan-5alpha-ol and cholestan-3beta, 5alpha-diol also show an ion at m/e 332 which, however, is of relatively low abundance. The ion in question appears to arise from fragmentation processes which are characteristics of 5alpha-hydroxysteroids. A similar fragmentation has been found to occur in cases of C-4 and C-6beta-alkylated 5alpha-hysroxy-cholestan-3-ones. The results of isotopic labeling, high resolution and metastable ion defocusing studies are discussed in terms of the origin of several of the ions in the spectra of the various compounds."} {"id": "PMID:1260961", "title": "Synthesis of DL-2,3-diacyloxypropylphosphonyl-cholines from DL-2,3-diacyloxyiodopropanes.", "content": "The chemical synthesis of racemic diacyloxypropylphosphonylcholines having octanoyl, myristoyl, oleoyl and stearoyl groups is described. The route involved reaction of dioactanoyloxy-dimyristoyloxy-dioleoyloxy-, and distearoyloxpropyliodide with tris (trimethylsilyl) phosphite to yield the corresponding bis (trimethylsilyl) phosphonate. Removal of the trimethylsilyl groups by neutral aqueous hydrolysis gave the free diacylpropylphosphonic acids, which, when treated with choline toluenesulfonate, yielded the desired dioctanoyloxy-, dimyristoyloxy-, dioleoyloxy-, and distearoyloxypropylphosphonylcholines. The paper also describes the synthesis of 2-octadecyleicosylphosphorylcholine.", "contents": "Synthesis of DL-2,3-diacyloxypropylphosphonyl-cholines from DL-2,3-diacyloxyiodopropanes. The chemical synthesis of racemic diacyloxypropylphosphonylcholines having octanoyl, myristoyl, oleoyl and stearoyl groups is described. The route involved reaction of dioactanoyloxy-dimyristoyloxy-dioleoyloxy-, and distearoyloxpropyliodide with tris (trimethylsilyl) phosphite to yield the corresponding bis (trimethylsilyl) phosphonate. Removal of the trimethylsilyl groups by neutral aqueous hydrolysis gave the free diacylpropylphosphonic acids, which, when treated with choline toluenesulfonate, yielded the desired dioctanoyloxy-, dimyristoyloxy-, dioleoyloxy-, and distearoyloxypropylphosphonylcholines. The paper also describes the synthesis of 2-octadecyleicosylphosphorylcholine."} {"id": "PMID:1260962", "title": "Diesters of alkane diols and 2-hydroxy fatty acids: identification and discrimination of isomers with the aid of NMR spectroscopy.", "content": "High resolution nuclear magnetic resonance spectroscopy has been shown to be extremely useful for the identification and discrimination of naturally occurring diesters of 1,2- and 2,3-alkanediols as well as for fatty alkyl esters of acylated 2-hydroxy fatty acids. A comparison of 220 MHz spectra of 1,2 and erythro- 2,3-alkanediol diesters exhibits the following distinguishing features: (1) two non-equivalent methylene protons from the glycol group of 1,2-alkanediol diesters resonate at 3.87 ppm and 4.17 ppm respectively while these resonances are completely absent in the spectrum of 2,3-isomer; (2) methylene protons adjacent to esther carbonyl groups appear as two overlapping triplets at 2.22 ppm in 1,2-alkanediol diesters while the corresponding protons in the 2,3-isomer are displayed as two partially overlapping triplets centered at 2.15 ppm and 2.2 ppm respectively; and (3) methyl protons adjacent to glycol group in 2,3-isomer appear as downfield doublet at 1.13 ppm; this downfield doublet is not shown by 1,2-alkanediol diesters. Erythro- and threo-2,3-alkanediol diesters have also been distinguished from each other; two alpha-methylenes in erythro isomers appear as partially overlapping triplets while these protons in threo isomer display an apparent quartet centered at 2.22 ppm. Fatty alkyl esters of acylated 2-hydroxy fatty acids display a triplet at 4.79 for 2-position methylene proton, a distinguishing feature not shown by diacyl alkanediols. A distinction between diester lipids and other classes of neutral lipids has also been achieved by the study of nuclear magnetic resonance spectra, particularly in the region of 3-6 ppm.", "contents": "Diesters of alkane diols and 2-hydroxy fatty acids: identification and discrimination of isomers with the aid of NMR spectroscopy. High resolution nuclear magnetic resonance spectroscopy has been shown to be extremely useful for the identification and discrimination of naturally occurring diesters of 1,2- and 2,3-alkanediols as well as for fatty alkyl esters of acylated 2-hydroxy fatty acids. A comparison of 220 MHz spectra of 1,2 and erythro- 2,3-alkanediol diesters exhibits the following distinguishing features: (1) two non-equivalent methylene protons from the glycol group of 1,2-alkanediol diesters resonate at 3.87 ppm and 4.17 ppm respectively while these resonances are completely absent in the spectrum of 2,3-isomer; (2) methylene protons adjacent to esther carbonyl groups appear as two overlapping triplets at 2.22 ppm in 1,2-alkanediol diesters while the corresponding protons in the 2,3-isomer are displayed as two partially overlapping triplets centered at 2.15 ppm and 2.2 ppm respectively; and (3) methyl protons adjacent to glycol group in 2,3-isomer appear as downfield doublet at 1.13 ppm; this downfield doublet is not shown by 1,2-alkanediol diesters. Erythro- and threo-2,3-alkanediol diesters have also been distinguished from each other; two alpha-methylenes in erythro isomers appear as partially overlapping triplets while these protons in threo isomer display an apparent quartet centered at 2.22 ppm. Fatty alkyl esters of acylated 2-hydroxy fatty acids display a triplet at 4.79 for 2-position methylene proton, a distinguishing feature not shown by diacyl alkanediols. A distinction between diester lipids and other classes of neutral lipids has also been achieved by the study of nuclear magnetic resonance spectra, particularly in the region of 3-6 ppm."} {"id": "PMID:1260963", "title": "The tilting of the hydrocarbon chains in a single bilayer of phospholipid.", "content": "The tilt angle of the hydrocarbon chains to the planes of a dipalmitoryl lecithin single bilayer and multilayers were estimated by the asymmetry of the electron diffraction patterns of respective hydrated specimens. The chains in a single bilayer were found to be perpendicular to the bilayer plane, whereas the chains in the multilayers were found to be tilted with respect to the normal of the plane. Thermal analysis data also supported this conclusion.", "contents": "The tilting of the hydrocarbon chains in a single bilayer of phospholipid. The tilt angle of the hydrocarbon chains to the planes of a dipalmitoryl lecithin single bilayer and multilayers were estimated by the asymmetry of the electron diffraction patterns of respective hydrated specimens. The chains in a single bilayer were found to be perpendicular to the bilayer plane, whereas the chains in the multilayers were found to be tilted with respect to the normal of the plane. Thermal analysis data also supported this conclusion."} {"id": "PMID:1260965", "title": "Reflex suppression of renin secretion during distention of cardiopulmonary receptors in dogs.", "content": "We studied the effect of brief periods of left atrial-pulmonary vein distention on the rate of renin secretion in sodium-restricted dogs anesthetized with chloralose and breathing spontaneously. Series 1 consisted of 32 trials in seven dogs with intact renal nerves and intact vagi. Renin secretion, calculated as the product of renal venous minus arterial renin activity (radioimmunoassay) times renal plasma flow (electromagnetic flowmeter), was depressed to 56% of control during atrial distention despite no change in arterial pressure, central venous pressure, or renal blood flow. Series 2 consisted of 58 trials in 12 dogs which had undergone unilateral renal denervation several days prior to the studies. Simultaneous, bilateral determinations indicated that renin secretion from the innervated kidney was depressed to 58% of control during atrial distention; secretion from the denervated kidney was unchanged. Series 3 consisted of 30 trials in six dogs with bilateral cervical vagotomy. Atrial distention evoked no changes in renin secretion. We conclude that left atrial distention reflexly reduces the rates of renin secretion via vagal afferent and renal sympathetic efferent pathways.", "contents": "Reflex suppression of renin secretion during distention of cardiopulmonary receptors in dogs. We studied the effect of brief periods of left atrial-pulmonary vein distention on the rate of renin secretion in sodium-restricted dogs anesthetized with chloralose and breathing spontaneously. Series 1 consisted of 32 trials in seven dogs with intact renal nerves and intact vagi. Renin secretion, calculated as the product of renal venous minus arterial renin activity (radioimmunoassay) times renal plasma flow (electromagnetic flowmeter), was depressed to 56% of control during atrial distention despite no change in arterial pressure, central venous pressure, or renal blood flow. Series 2 consisted of 58 trials in 12 dogs which had undergone unilateral renal denervation several days prior to the studies. Simultaneous, bilateral determinations indicated that renin secretion from the innervated kidney was depressed to 58% of control during atrial distention; secretion from the denervated kidney was unchanged. Series 3 consisted of 30 trials in six dogs with bilateral cervical vagotomy. Atrial distention evoked no changes in renin secretion. We conclude that left atrial distention reflexly reduces the rates of renin secretion via vagal afferent and renal sympathetic efferent pathways."} {"id": "PMID:1260966", "title": "Effects of activation sequence on the local recovery of ventricular excitability in the dog.", "content": "We measured refractory periods at ventricular sites in the dog heart during drive from ventricular test sites and during combined drive from the test sites and other ventricular sites or the atrium. We found that ventricular activation sequence caused significant alterations on refractory period. Combined drive from two sites which resulted in fusion complexes was associated with shorter refractory periods at the test sites than those observed during drive at the test sites only. Our findings are explicable because earlier excitation and consequent earlier recovery of surrounding areas during fusion beats exerts an electrotonic influence on test sites.", "contents": "Effects of activation sequence on the local recovery of ventricular excitability in the dog. We measured refractory periods at ventricular sites in the dog heart during drive from ventricular test sites and during combined drive from the test sites and other ventricular sites or the atrium. We found that ventricular activation sequence caused significant alterations on refractory period. Combined drive from two sites which resulted in fusion complexes was associated with shorter refractory periods at the test sites than those observed during drive at the test sites only. Our findings are explicable because earlier excitation and consequent earlier recovery of surrounding areas during fusion beats exerts an electrotonic influence on test sites."} {"id": "PMID:1260967", "title": "Effect of thoracic blood volume changes on steady state cardiac output.", "content": "We have investigated the extent to which shifts of blood volume out of or into the thoracic region influence the steady state cardiac output. The systemic circulation of anesthetized dogs was replaced with an artificial circuit which stimulated the pertinent mechanical characteristics of an intact circulation. As in the normal animal, the steady state venous return was proportional to the pressure gradient for venous return (i.e, mean systemic minus right atrial pressure). Cardiac function was altered either by administration of epinephrine or by changes in left ventricular afterload. At a constant mean aortic pressure of 100 mm Hg, epinephrine administration increased the steady state cardiac output by 55%. Half of this increase resulted from the lowered mean right atrial pressure (caused by improved cardiac function); the remainder resulted from an increased mean systemic pressure (caused by the volume shift to the systemic circulation). Increases in afterload transferred sufficient volume to the heart-lung compartment to reduce significantly the mean systemic pressure and, hence, the steady state venous return. Our results indicate that the heart-lung compartment contains a significant volume which is under cardiac control. In addition to being able to alter the right atrial pressure, the heart can modulate the steady state cardiac output by adjusting the mean systemic pressure. To this degree the heart can adjust its own venous return.", "contents": "Effect of thoracic blood volume changes on steady state cardiac output. We have investigated the extent to which shifts of blood volume out of or into the thoracic region influence the steady state cardiac output. The systemic circulation of anesthetized dogs was replaced with an artificial circuit which stimulated the pertinent mechanical characteristics of an intact circulation. As in the normal animal, the steady state venous return was proportional to the pressure gradient for venous return (i.e, mean systemic minus right atrial pressure). Cardiac function was altered either by administration of epinephrine or by changes in left ventricular afterload. At a constant mean aortic pressure of 100 mm Hg, epinephrine administration increased the steady state cardiac output by 55%. Half of this increase resulted from the lowered mean right atrial pressure (caused by improved cardiac function); the remainder resulted from an increased mean systemic pressure (caused by the volume shift to the systemic circulation). Increases in afterload transferred sufficient volume to the heart-lung compartment to reduce significantly the mean systemic pressure and, hence, the steady state venous return. Our results indicate that the heart-lung compartment contains a significant volume which is under cardiac control. In addition to being able to alter the right atrial pressure, the heart can modulate the steady state cardiac output by adjusting the mean systemic pressure. To this degree the heart can adjust its own venous return."} {"id": "PMID:1260968", "title": "Relationships between pressure and flow in the umbilical and uterine circulations of the sheep.", "content": "We studied the relationship of fetal and maternal vascular pressures to umbilical and uterine blood flow in the unanesthetized ewe and in the sheep fetus in utero by placing electromagnetic flow transducers around both the common umbilical and uterine arteries. Reductions in umbilical arterial pressure or elevations in umbilical venous pressure decreased umbilical blood flow without affecting either the uterine arterial blood flow or other maternal cardiovascular variables which were studied. Elevations in uterine venous pressure or reductions in uterine arterial pressure decreased uterine arterial flow but these interventions had no effect on umbilical blood flow until fetal hypoxemia and bradycardia occurred. When the bradycardia of the fetal hypoxic response was inhibited by atropine, alterations in maternal vascular pressure had no effect on umbilical arterial flow. These data do not support the presence of a \"sluice\" or \"waterfall\" effect in the umbilical-placental circulation of the sheep fetus in utero.", "contents": "Relationships between pressure and flow in the umbilical and uterine circulations of the sheep. We studied the relationship of fetal and maternal vascular pressures to umbilical and uterine blood flow in the unanesthetized ewe and in the sheep fetus in utero by placing electromagnetic flow transducers around both the common umbilical and uterine arteries. Reductions in umbilical arterial pressure or elevations in umbilical venous pressure decreased umbilical blood flow without affecting either the uterine arterial blood flow or other maternal cardiovascular variables which were studied. Elevations in uterine venous pressure or reductions in uterine arterial pressure decreased uterine arterial flow but these interventions had no effect on umbilical blood flow until fetal hypoxemia and bradycardia occurred. When the bradycardia of the fetal hypoxic response was inhibited by atropine, alterations in maternal vascular pressure had no effect on umbilical arterial flow. These data do not support the presence of a \"sluice\" or \"waterfall\" effect in the umbilical-placental circulation of the sheep fetus in utero."} {"id": "PMID:1260969", "title": "The vascular basis for acute renal failure in the rat. Preglomerular and postglomerular vasoconstriction.", "content": "Myohemoglobinuric acute renal failure (ARF) was induced in dehydrated, salt-deficient, salt-loaded, and untreated rats by intramuscular injection of glycerol, and the renal vasculature was studied after 24 hours. Kidneys were prepared for examination by rapid freezing in vivo to -160 degrees C and freeze substitution in -80 degrees C alcohol, and by perfusion fixation with 1% glutaraldehyde in Ringer's solution at 120 mm Hg. Frozen kidneys were examined by light microscopy after paraffin and epoxy resin embedding. Techniques used in examining the perfusion-fixed kidneys were: (1) vascular injection with silicone rubber and clearing in glycerol, (2) electron microscopy, and (3) morphometric evaluation of lumen to wall area ratios of glomerular arterioles. Kidneys of all rats with ARF showed renal cortical arterial and glomerular arteriolar (afferent and efferent) vasoconstriction. The degree of constriction, estimated by lumen to wall ratios, correlated with the degree of azotemia (r = -0.71; P less than 0.001). Differences between all ARF groups and respective controls were highly significant (P less than 0.001). Vasoconstriction was maximal in the dehydrated group, intermediate in the untreated and Na-deficient rats, and lowest in the salt-loaded animals. Glomerular and peritubular capillaries were patent and free of endothelial swelling or thrombi. Glomerular basement membranes and epithelial foot processes showed no morphological alterations. The observations suggest that marked pre- and postglomerular vasoconstriction occurs in established myohemoglobinuric ARF, that it is related to azotemia, and that mechanical vascular obstruction does not play a major role in this experimental model.", "contents": "The vascular basis for acute renal failure in the rat. Preglomerular and postglomerular vasoconstriction. Myohemoglobinuric acute renal failure (ARF) was induced in dehydrated, salt-deficient, salt-loaded, and untreated rats by intramuscular injection of glycerol, and the renal vasculature was studied after 24 hours. Kidneys were prepared for examination by rapid freezing in vivo to -160 degrees C and freeze substitution in -80 degrees C alcohol, and by perfusion fixation with 1% glutaraldehyde in Ringer's solution at 120 mm Hg. Frozen kidneys were examined by light microscopy after paraffin and epoxy resin embedding. Techniques used in examining the perfusion-fixed kidneys were: (1) vascular injection with silicone rubber and clearing in glycerol, (2) electron microscopy, and (3) morphometric evaluation of lumen to wall area ratios of glomerular arterioles. Kidneys of all rats with ARF showed renal cortical arterial and glomerular arteriolar (afferent and efferent) vasoconstriction. The degree of constriction, estimated by lumen to wall ratios, correlated with the degree of azotemia (r = -0.71; P less than 0.001). Differences between all ARF groups and respective controls were highly significant (P less than 0.001). Vasoconstriction was maximal in the dehydrated group, intermediate in the untreated and Na-deficient rats, and lowest in the salt-loaded animals. Glomerular and peritubular capillaries were patent and free of endothelial swelling or thrombi. Glomerular basement membranes and epithelial foot processes showed no morphological alterations. The observations suggest that marked pre- and postglomerular vasoconstriction occurs in established myohemoglobinuric ARF, that it is related to azotemia, and that mechanical vascular obstruction does not play a major role in this experimental model."} {"id": "PMID:1260970", "title": "Length-induced changes in activation during contraction. A study of mechanical oscillations in strontium-mediated contractions of cat and frog heart muscle.", "content": "The plateau phase of prolonged Sr-mediated contractions of preparations of cat and frog heart muscle was used to study the transient response to abrupt changes in load or length. An oscillatory response (total amplitude equal to or less than 5% Lmax) was obtained. Isotonic oscillations were less damped than their isometric counterparts, implying positive feedback and thus a causal role of the perturbation in length. Oscillation frequency was 2-3 HZ at 29 degrees C (Q 10, 2-3); it could be increased by epinephrine or caffeine, independently of their effects on extent of shortening; it otherwise changed as a generally constant function of the length at which the oscillation occurred, whether this was altered by changes in extracellular [Sr], frequency of contraction, or load (independent of the direction and magnitude of the preceding load step). Similar oscillatory responses were induced during Sr- or Ca-mediated contractures. Cat muscles showed an additional slower component to the oscillatory response. Transient augmentation of the velocity-length relationship after abrupt reduction in load, previously described for twitch contractions under certain conditions, appears to be analogous to the first phase of the oscillatory response studied here. Our findings indicate that the oscillation is not attributable to any mechanism intrinsic to myofilament interaction, but rather that it involves length-induced changes in the level of activation, probably mediated by Ca2+ or Sr2+. We conclude that length influences the level of activation during contraction of heart muscle.", "contents": "Length-induced changes in activation during contraction. A study of mechanical oscillations in strontium-mediated contractions of cat and frog heart muscle. The plateau phase of prolonged Sr-mediated contractions of preparations of cat and frog heart muscle was used to study the transient response to abrupt changes in load or length. An oscillatory response (total amplitude equal to or less than 5% Lmax) was obtained. Isotonic oscillations were less damped than their isometric counterparts, implying positive feedback and thus a causal role of the perturbation in length. Oscillation frequency was 2-3 HZ at 29 degrees C (Q 10, 2-3); it could be increased by epinephrine or caffeine, independently of their effects on extent of shortening; it otherwise changed as a generally constant function of the length at which the oscillation occurred, whether this was altered by changes in extracellular [Sr], frequency of contraction, or load (independent of the direction and magnitude of the preceding load step). Similar oscillatory responses were induced during Sr- or Ca-mediated contractures. Cat muscles showed an additional slower component to the oscillatory response. Transient augmentation of the velocity-length relationship after abrupt reduction in load, previously described for twitch contractions under certain conditions, appears to be analogous to the first phase of the oscillatory response studied here. Our findings indicate that the oscillation is not attributable to any mechanism intrinsic to myofilament interaction, but rather that it involves length-induced changes in the level of activation, probably mediated by Ca2+ or Sr2+. We conclude that length influences the level of activation during contraction of heart muscle."} {"id": "PMID:1260971", "title": "The pumping ability of the left heart and the effect of coronary occlusion.", "content": "In an isolated preparation of cat heart we studied the pumping capacity of the left heart while left atrial filling pressure was kept constant. We used the source impedance concept to quantify the pumping capacity. In this source impedance concept the relation between left ventricular output and left ventricular pressure is given by the formula (see article) where Zs = source impedance, Plv = left ventricular pressure, Iao = flow in the ascending aorta, and omega = 2pif, f being frequency.. The pressure obtained at zero flow is called the hydromotive pressure (HMP). Only the mean values of pressure and flow were studied. We studied the behavior of 10 hearts in three different experimental situations and in the following sequence: (1) control conditions, (2) after ligating a part of the left coronary arterial system, and (3) after restoring left ventricular output to control level by raising left atrial filling pressure. It was found that source resistance was not significantly different in the three situations but that mean hydromotive pressure (HMP) was significantly lower after ligation of a part of the left coronary arterial system. It was concluded that the decrease in pumping capacity of the left heart after infarction can be compensated for almost completely by an increase in left atrial filling pressure. This compensating mechanism therefore seems to be very efficient.", "contents": "The pumping ability of the left heart and the effect of coronary occlusion. In an isolated preparation of cat heart we studied the pumping capacity of the left heart while left atrial filling pressure was kept constant. We used the source impedance concept to quantify the pumping capacity. In this source impedance concept the relation between left ventricular output and left ventricular pressure is given by the formula (see article) where Zs = source impedance, Plv = left ventricular pressure, Iao = flow in the ascending aorta, and omega = 2pif, f being frequency.. The pressure obtained at zero flow is called the hydromotive pressure (HMP). Only the mean values of pressure and flow were studied. We studied the behavior of 10 hearts in three different experimental situations and in the following sequence: (1) control conditions, (2) after ligating a part of the left coronary arterial system, and (3) after restoring left ventricular output to control level by raising left atrial filling pressure. It was found that source resistance was not significantly different in the three situations but that mean hydromotive pressure (HMP) was significantly lower after ligation of a part of the left coronary arterial system. It was concluded that the decrease in pumping capacity of the left heart after infarction can be compensated for almost completely by an increase in left atrial filling pressure. This compensating mechanism therefore seems to be very efficient."} {"id": "PMID:1260972", "title": "Electrophysiological and antiarrhythmic effects of propranolol in canine acute myocardial ischemia.", "content": "To correlate the antiarrhythmic and electrophysiological effects of propranolol in acute myocardial ischemia, we examined the effects of temporary (15-minute) ligations of the left anterior descending coronary artery in studies on 15 dogs. We recorded bipolar electrograms and monophasic action potentials from the ischemic and normal zones and measured the intervals from the onset of QRS in a standard electrocardiogram lead to the major deflection of electrograms recorded from the ischemic and normal zones. We also determined monophasic action potential duration (APD) and effective refractory period (ERP). Data for control ligations were compared to those during which propranolol, 40 mug/kg, was administered intravenously immediately after ligation. Propranolol reduced the mean number of ventricular beats per minute (from 15 to 6) (P less than 0.01). Propranolol slowed conduction in the ischemic zone (by 10 msec at peak effect, P less than 0.01) and had no or only a very slight effect (by 1-msec at 15 minutes, P less than 0.05) on conduction in the normal zone. Propranolol also prolonged APD in the ischemic (32-msec) and normal (14-msec) zones (P less than 0.01), prolonged ERP in the ischemic (41-msec) and normal (20-msec) zones (P less than 0.01), and reduced the APD/ERP ratio in the ischemic (1.62 to 1.47) (P less than 0.01) and normal (1.62 to 1.55) (P less than 0.05) zones. During the control ligation, APD in the ischemic zone was 25 msec shorter than in the normal zone (P less than 0.01), but with propranolol the difference was not significant. The effects of propranolol in slowing conduction in the ischemic zone, in prolonging refractoriness, in reducing APD/ERP, and in reducing the disparity in APD between ischemic and normal zones may explain its demonstrated antiarrhythmic effects in acute myocardial ischemia.", "contents": "Electrophysiological and antiarrhythmic effects of propranolol in canine acute myocardial ischemia. To correlate the antiarrhythmic and electrophysiological effects of propranolol in acute myocardial ischemia, we examined the effects of temporary (15-minute) ligations of the left anterior descending coronary artery in studies on 15 dogs. We recorded bipolar electrograms and monophasic action potentials from the ischemic and normal zones and measured the intervals from the onset of QRS in a standard electrocardiogram lead to the major deflection of electrograms recorded from the ischemic and normal zones. We also determined monophasic action potential duration (APD) and effective refractory period (ERP). Data for control ligations were compared to those during which propranolol, 40 mug/kg, was administered intravenously immediately after ligation. Propranolol reduced the mean number of ventricular beats per minute (from 15 to 6) (P less than 0.01). Propranolol slowed conduction in the ischemic zone (by 10 msec at peak effect, P less than 0.01) and had no or only a very slight effect (by 1-msec at 15 minutes, P less than 0.05) on conduction in the normal zone. Propranolol also prolonged APD in the ischemic (32-msec) and normal (14-msec) zones (P less than 0.01), prolonged ERP in the ischemic (41-msec) and normal (20-msec) zones (P less than 0.01), and reduced the APD/ERP ratio in the ischemic (1.62 to 1.47) (P less than 0.01) and normal (1.62 to 1.55) (P less than 0.05) zones. During the control ligation, APD in the ischemic zone was 25 msec shorter than in the normal zone (P less than 0.01), but with propranolol the difference was not significant. The effects of propranolol in slowing conduction in the ischemic zone, in prolonging refractoriness, in reducing APD/ERP, and in reducing the disparity in APD between ischemic and normal zones may explain its demonstrated antiarrhythmic effects in acute myocardial ischemia."} {"id": "PMID:1260973", "title": "Effects on myocardial contractility of blood-borne material released from the feline small intestine in simulated shock.", "content": "There is a pronounced derangement in cardiovascular function in the cat after a 2- or 3-hour period during which shock is simulated in the small intestine by regional hypotension (BP = 30-35 mm Hg) during activation of vasoconstrictor nerve fibers. It has been proposed that these effects are caused by blood-borne cardiode-pressant substance(s) released from the \"shocked\" small intestine. To obtain further evidence for this hypothesis we performed a study on two heart preparations in vitro. Rabbit papillary muscles or isolated beating rat hearts were exposed to intestinal venous plasma obtained from control cats and from cats subjected to simulated intestinal shock for 2 or 3 hours. while control plasma induced only a slight depression of myocardial contractility, plasma from \"shocked\" intestine caused a significant decrease in peak isometric tension of the papillary muscles or a fall in systolic pressure of the rat hearts. Since the experiments on papillary muscle indicated that time to peak tension was largely unaffected by the plasma samples, we conclude that the feline intestine in shock releases material into blood that exerts a negative inotropic effect on the myocardium.", "contents": "Effects on myocardial contractility of blood-borne material released from the feline small intestine in simulated shock. There is a pronounced derangement in cardiovascular function in the cat after a 2- or 3-hour period during which shock is simulated in the small intestine by regional hypotension (BP = 30-35 mm Hg) during activation of vasoconstrictor nerve fibers. It has been proposed that these effects are caused by blood-borne cardiode-pressant substance(s) released from the \"shocked\" small intestine. To obtain further evidence for this hypothesis we performed a study on two heart preparations in vitro. Rabbit papillary muscles or isolated beating rat hearts were exposed to intestinal venous plasma obtained from control cats and from cats subjected to simulated intestinal shock for 2 or 3 hours. while control plasma induced only a slight depression of myocardial contractility, plasma from \"shocked\" intestine caused a significant decrease in peak isometric tension of the papillary muscles or a fall in systolic pressure of the rat hearts. Since the experiments on papillary muscle indicated that time to peak tension was largely unaffected by the plasma samples, we conclude that the feline intestine in shock releases material into blood that exerts a negative inotropic effect on the myocardium."} {"id": "PMID:1260974", "title": "Blood pressure and plasma angiotensin II concentration after renal artery constriction and angiotensin infusion in the dog. (5-Isoleucine)angiotensin II and its breakdown fragments in dog blood.", "content": "We measured arterial plasma angiotensin II concentration, renal blood flow, and arterial blood pressure in six conscious dogs during intravenous infusion of angiotensin II (5, 10, and 20 ng/kg per min). The same measurements were made on a different occasion in the same six animals, while they were conscious, before and during constriction of a main renal artery. Arterial blood pressure and plasma angiotensin II rose and renal blood flow decreased in both experiments. The similarity of regressions for plasma angiotensin II concentration and arterial blood pressure in the two experiments strongly suggests that the rise of circulating angiotensin II after renal artery constriction is sufficient to account for the hypertension by its direct pressor action. As discussed, a different mechanism seems likely to be involved in the later stages of renal hypertension. Angiotensin II is more likely to be in the 5-isoleucine form than in the 5-valine form in the dog. In contrast to the rat, plasma concentrations of the heptapeptide (angiotensin III), hexapeptide, and pentapeptide fragments of angiotensin II are low in the dog.", "contents": "Blood pressure and plasma angiotensin II concentration after renal artery constriction and angiotensin infusion in the dog. (5-Isoleucine)angiotensin II and its breakdown fragments in dog blood. We measured arterial plasma angiotensin II concentration, renal blood flow, and arterial blood pressure in six conscious dogs during intravenous infusion of angiotensin II (5, 10, and 20 ng/kg per min). The same measurements were made on a different occasion in the same six animals, while they were conscious, before and during constriction of a main renal artery. Arterial blood pressure and plasma angiotensin II rose and renal blood flow decreased in both experiments. The similarity of regressions for plasma angiotensin II concentration and arterial blood pressure in the two experiments strongly suggests that the rise of circulating angiotensin II after renal artery constriction is sufficient to account for the hypertension by its direct pressor action. As discussed, a different mechanism seems likely to be involved in the later stages of renal hypertension. Angiotensin II is more likely to be in the 5-isoleucine form than in the 5-valine form in the dog. In contrast to the rat, plasma concentrations of the heptapeptide (angiotensin III), hexapeptide, and pentapeptide fragments of angiotensin II are low in the dog."} {"id": "PMID:1260975", "title": "The role of arterial baroreceptors in mediating the cardiovascular response to a cardiac glycoside in conscious dogs.", "content": "To determine the role of the arterial baroreceptor reflex in mediating the cardiovascular response to a cardiac glycoside, we examined the effects of ouabain (G-strophanthin), 17.5 mug/kg, iv, on direct and continuous measurements of left ventricular diameters, pressures, velocity of shortening, (dP/dt)/P, arterial pressure, cardiac output, and total peripheral resistance. These studies were conducted on healthy conscious dogs before and after total arterial baroreceptor denervation (TABD). Maximal pressor effects were observed in the first 3-5 minutes; mean arterial pressure increased by 11 +/- 1 mm Hg in normal dogs compared to 33 +/- 4 mm Hg in denervated dogs. In intact dogs at this time heart rate decreased by 18 +/- 2 beats/min and cardiac output fell by 18 +/- 3%; these values gradually returned toward control over 15-30 minutes. When heart rate was kept constant, cardiac output did not fall after injection of ouabain. In contrast, heart rate and cardiac output did not change significantly after ouabain in dogs with TABD. The maximal effects on the contractile state of the heart occurred between 15-30 minutes and were similar in both groups. Arterial baroreceptor reflexes appear to be responsible for the reduction in heart rate and cardiac output caused by administration of ouabain to the intact dog. They exert an important buffering action on the vasopressor effect but a less important action on the inotropic response.", "contents": "The role of arterial baroreceptors in mediating the cardiovascular response to a cardiac glycoside in conscious dogs. To determine the role of the arterial baroreceptor reflex in mediating the cardiovascular response to a cardiac glycoside, we examined the effects of ouabain (G-strophanthin), 17.5 mug/kg, iv, on direct and continuous measurements of left ventricular diameters, pressures, velocity of shortening, (dP/dt)/P, arterial pressure, cardiac output, and total peripheral resistance. These studies were conducted on healthy conscious dogs before and after total arterial baroreceptor denervation (TABD). Maximal pressor effects were observed in the first 3-5 minutes; mean arterial pressure increased by 11 +/- 1 mm Hg in normal dogs compared to 33 +/- 4 mm Hg in denervated dogs. In intact dogs at this time heart rate decreased by 18 +/- 2 beats/min and cardiac output fell by 18 +/- 3%; these values gradually returned toward control over 15-30 minutes. When heart rate was kept constant, cardiac output did not fall after injection of ouabain. In contrast, heart rate and cardiac output did not change significantly after ouabain in dogs with TABD. The maximal effects on the contractile state of the heart occurred between 15-30 minutes and were similar in both groups. Arterial baroreceptor reflexes appear to be responsible for the reduction in heart rate and cardiac output caused by administration of ouabain to the intact dog. They exert an important buffering action on the vasopressor effect but a less important action on the inotropic response."} {"id": "PMID:1260976", "title": "Report of the Inter-Society Commission for Heart Disease Resources. Optimal resources for vascular surgery--a supplement.", "content": "This supplement is an updated and expanded planning and optimal resource guideline for vascular surgery. Activities relating to examination and certification in vascular surgery are reviewed and hospital resource requirements are identified for different categories of vascular operations. There is a detailed summary of results of common vascular operations as reported by leading vascular surgeons. The statement will be of value in planning and organizing vascular surgery programs and in assessing the results of vascular operations locally.", "contents": "Report of the Inter-Society Commission for Heart Disease Resources. Optimal resources for vascular surgery--a supplement. This supplement is an updated and expanded planning and optimal resource guideline for vascular surgery. Activities relating to examination and certification in vascular surgery are reviewed and hospital resource requirements are identified for different categories of vascular operations. There is a detailed summary of results of common vascular operations as reported by leading vascular surgeons. The statement will be of value in planning and organizing vascular surgery programs and in assessing the results of vascular operations locally."} {"id": "PMID:1260977", "title": "The contribution of tricuspid valve closure to the first heart sound. An intracardiac micromanometer study.", "content": "The sound-pressure correlates of the second high frequency component of a split first heart sound (S1) were investigated in 27 patients. An external phonocardiogram was recorded with high fidelity sound and pressure from the left and right atria in 21 patients, from the pulmonary artery in 14 of these, and from the central aorta in 11. In the remaining six patients, high fidelity recordings from the central aorta and right-sided chambers were obtained with an external phonocardiogram. The external component of S1 that coincided with a left atrial C wave and \"internal sound\" was defined as M1. In those cases where the left atrial pressure was not recorded, this component could be identified by a low frequency transient in the central aortic pressure trace. The other external high frequency component of S1 that was synchronous with a separate right atrial C wave and \"internal sound\" was defined as T1; with two exceptions, M1 preceded T1. The two exceptions which caused reversal of this order, so that T1 preceded M1, were due to chronic left bundle branch block and mitral stenosis. In both cases, T1 was shown to be distinctly separated from the upstroke of pressure rise in the central aorta. This finding was also demonstrated in three cases of right bundle branch block and one case with aortic valvular disease. The usual asynchrony of ventricular contraction was altered by induction of ventricular premature systoles; the separation of externally identifiable M1 and T1 components and their internal markers was predictably altered by this maneuver. The occurrence of T1 was variable in relation to the upstroke of the pulmonary artery pressure, which suggests that it is not related to pulmonic ejection. It is concluded that micromanometrically recorded right and left atrial C waves can serve as markers for externally recordable M1 and T1 components of the first heart sound. In addition, T1 is frequently an externally recordable and audible event.", "contents": "The contribution of tricuspid valve closure to the first heart sound. An intracardiac micromanometer study. The sound-pressure correlates of the second high frequency component of a split first heart sound (S1) were investigated in 27 patients. An external phonocardiogram was recorded with high fidelity sound and pressure from the left and right atria in 21 patients, from the pulmonary artery in 14 of these, and from the central aorta in 11. In the remaining six patients, high fidelity recordings from the central aorta and right-sided chambers were obtained with an external phonocardiogram. The external component of S1 that coincided with a left atrial C wave and \"internal sound\" was defined as M1. In those cases where the left atrial pressure was not recorded, this component could be identified by a low frequency transient in the central aortic pressure trace. The other external high frequency component of S1 that was synchronous with a separate right atrial C wave and \"internal sound\" was defined as T1; with two exceptions, M1 preceded T1. The two exceptions which caused reversal of this order, so that T1 preceded M1, were due to chronic left bundle branch block and mitral stenosis. In both cases, T1 was shown to be distinctly separated from the upstroke of pressure rise in the central aorta. This finding was also demonstrated in three cases of right bundle branch block and one case with aortic valvular disease. The usual asynchrony of ventricular contraction was altered by induction of ventricular premature systoles; the separation of externally identifiable M1 and T1 components and their internal markers was predictably altered by this maneuver. The occurrence of T1 was variable in relation to the upstroke of the pulmonary artery pressure, which suggests that it is not related to pulmonic ejection. It is concluded that micromanometrically recorded right and left atrial C waves can serve as markers for externally recordable M1 and T1 components of the first heart sound. In addition, T1 is frequently an externally recordable and audible event."} {"id": "PMID:1260978", "title": "Familial atrial septal defect with prolonged atrioventricular conduction.", "content": "This report describes a family with frequent recurrence of congenital heart disease in multiple generations. Eight members had atrial septal defect (ASD) of the fossa ovalis type and seven members had other forms of congenital heart disease. One branch of the pedigree showed a predominance of ASD with prolonged atrioventricular (A-V) conduction and initially suggested an autosomal dominant gene effect. A variety of other forms of congenital heart disease were found in several first degree relatives of those with ASD as well as in more distant relatives. The variability of congenital heart disease in this pedigree is compatible with the polygenic mode of inheritance. Definition of the inheritability of congenital heart disease in a specific family has important consequences in the determination of the recurrence risks for all family members.", "contents": "Familial atrial septal defect with prolonged atrioventricular conduction. This report describes a family with frequent recurrence of congenital heart disease in multiple generations. Eight members had atrial septal defect (ASD) of the fossa ovalis type and seven members had other forms of congenital heart disease. One branch of the pedigree showed a predominance of ASD with prolonged atrioventricular (A-V) conduction and initially suggested an autosomal dominant gene effect. A variety of other forms of congenital heart disease were found in several first degree relatives of those with ASD as well as in more distant relatives. The variability of congenital heart disease in this pedigree is compatible with the polygenic mode of inheritance. Definition of the inheritability of congenital heart disease in a specific family has important consequences in the determination of the recurrence risks for all family members."} {"id": "PMID:1260979", "title": "Electrophysiologic evaluation of sinus node function in patients with sinus node dysfunction.", "content": "Twenty patients of mean age 66.2 years, with suspected sinus node dysfunction, underwent extensive electrophysiologic study. Sinus bradycardia (18), sinus pauses (3), and sinoatrial block (1) were identified in their ECGs prior to study. Also 11 patients had some abnormality of atrioventricular nodal and/or intraventricular conduction prior to study. At the time of electrophysiological study, 10/20 patients (50%) had a mean cycle length exceeding 1000 msec, and mean P-V interval exceeded 210 msec in 7/20 (35%). The estimated \"sinoatrial conduction time\" exceeded 215 msec in 6/16 (38%) patients. The maximum first escape cycle following pacing at six different rates exceeded a value equal 1.3 X the mean value of the control cycle length + 101 msec (slope of regression line + Y intercept + 1 SD) in 13/9 (68%) patients. Nineteen patients received 1 mg atropine intravenously and mean cycle length decreased by 19%, from 891 +/- 175.8 msec to 718 +/- 182.9 msec. Graded infusion of isoproterenol was employed in 19 patients; four patients required an infusion rate greater than 28.3 ng/kg/min to produce a 20% decrease in spontaneous sinus cycle length. These data would indicate that a variety of interventions are required to characterize the disturbance of sinus node automaticiy and sinoatrial conduction in patients with sinus node dysfunction.", "contents": "Electrophysiologic evaluation of sinus node function in patients with sinus node dysfunction. Twenty patients of mean age 66.2 years, with suspected sinus node dysfunction, underwent extensive electrophysiologic study. Sinus bradycardia (18), sinus pauses (3), and sinoatrial block (1) were identified in their ECGs prior to study. Also 11 patients had some abnormality of atrioventricular nodal and/or intraventricular conduction prior to study. At the time of electrophysiological study, 10/20 patients (50%) had a mean cycle length exceeding 1000 msec, and mean P-V interval exceeded 210 msec in 7/20 (35%). The estimated \"sinoatrial conduction time\" exceeded 215 msec in 6/16 (38%) patients. The maximum first escape cycle following pacing at six different rates exceeded a value equal 1.3 X the mean value of the control cycle length + 101 msec (slope of regression line + Y intercept + 1 SD) in 13/9 (68%) patients. Nineteen patients received 1 mg atropine intravenously and mean cycle length decreased by 19%, from 891 +/- 175.8 msec to 718 +/- 182.9 msec. Graded infusion of isoproterenol was employed in 19 patients; four patients required an infusion rate greater than 28.3 ng/kg/min to produce a 20% decrease in spontaneous sinus cycle length. These data would indicate that a variety of interventions are required to characterize the disturbance of sinus node automaticiy and sinoatrial conduction in patients with sinus node dysfunction."} {"id": "PMID:1260980", "title": "Concealed intraventricular conduction in the His bundle electrogram.", "content": "Multiple areas of concealed intraventricular conduction are deduced on the basis of aftereffects observed in His bundle recordings. Electrocardiograms and His bundle recordings are presented from two patients with unstable bilateral bundle branch block, the instability of which depended on the interval at which ventricular depolarization was initiated by sinus or paced impulses. This circumstance allows postulation of 1) concealed transseptal retrograde penetration of the left bundle branch system; 2) concealed transseptal retrograde penetration of the right bundle branch system; 3) alternate beat Wenckebach phenomenon with two areas of block in the bundle branch system with concealed penetration of the proximal area; 4) concealed re-entry in the right bundle branch system during an H-V Wenckebach cycle with resetting of the sequence of 2:1 H-V block and return of the re-entry wave to the A-V node causing subsequent A-H block; 5) proximal 2:1 block and distal Wenckebach block producing only two consecutively blocked beats; and 6) infrahisian Wenckebach block with changes both in A-V conduction and QRS contour.", "contents": "Concealed intraventricular conduction in the His bundle electrogram. Multiple areas of concealed intraventricular conduction are deduced on the basis of aftereffects observed in His bundle recordings. Electrocardiograms and His bundle recordings are presented from two patients with unstable bilateral bundle branch block, the instability of which depended on the interval at which ventricular depolarization was initiated by sinus or paced impulses. This circumstance allows postulation of 1) concealed transseptal retrograde penetration of the left bundle branch system; 2) concealed transseptal retrograde penetration of the right bundle branch system; 3) alternate beat Wenckebach phenomenon with two areas of block in the bundle branch system with concealed penetration of the proximal area; 4) concealed re-entry in the right bundle branch system during an H-V Wenckebach cycle with resetting of the sequence of 2:1 H-V block and return of the re-entry wave to the A-V node causing subsequent A-H block; 5) proximal 2:1 block and distal Wenckebach block producing only two consecutively blocked beats; and 6) infrahisian Wenckebach block with changes both in A-V conduction and QRS contour."} {"id": "PMID:1260981", "title": "Incidence and significance of left anterior hemiblock complicating acute inferior wall myocardial infarction.", "content": "The hospital course and serial vectorcardiograms of 56 consecutive patients with acute inferior wall myocardial infarction were reviewed. Left anterior hemiblock (LAH) complicating inferior wall myocardial infarction was diagnosed by vectorcardiographic criteria. Seven patients (12.5%) developed LAH between the first and third hospital day, while 49 patients did not. There was no significant difference between these two groups when compared for age, sex, incidence of congestive heart failure, atrial and ventricular arrhythmias, atrioventricular (A-V) block, hospital mortality, and previous hypertension, diabetes mellitus, and myocardial infarction. We conclude that LAH is a relatively common complication of acute inferior wall myocardial infarction, with no apparent effect on the clinical course.", "contents": "Incidence and significance of left anterior hemiblock complicating acute inferior wall myocardial infarction. The hospital course and serial vectorcardiograms of 56 consecutive patients with acute inferior wall myocardial infarction were reviewed. Left anterior hemiblock (LAH) complicating inferior wall myocardial infarction was diagnosed by vectorcardiographic criteria. Seven patients (12.5%) developed LAH between the first and third hospital day, while 49 patients did not. There was no significant difference between these two groups when compared for age, sex, incidence of congestive heart failure, atrial and ventricular arrhythmias, atrioventricular (A-V) block, hospital mortality, and previous hypertension, diabetes mellitus, and myocardial infarction. We conclude that LAH is a relatively common complication of acute inferior wall myocardial infarction, with no apparent effect on the clinical course."} {"id": "PMID:1260982", "title": "Protection of the sinus node in Mustard's operation.", "content": "The occurrence of dysrhythmias after the Mustard operation for transposition of the great arteries was compared in 70 patients operated upon before and 58 patients operated upon after January 1972 when surgical modifications aimed at preserving the sino-atrial node and its arterial supply were initiated. The surgical modifications included changing the site of the superior vena cava (SVC) cannulation away from the SVC-right atrial junction, incision into the right atrial wall anterior to the sulcus terminalis, and sewing of the superior part of the baffle patch away from the sino-atrial node area. A significant decrease in the incidence of dysrhythmias occurred in the group of patients operated upon after the surgical modifications. The modifications in surgical technique have reduced but not avoided dysrhythmias.", "contents": "Protection of the sinus node in Mustard's operation. The occurrence of dysrhythmias after the Mustard operation for transposition of the great arteries was compared in 70 patients operated upon before and 58 patients operated upon after January 1972 when surgical modifications aimed at preserving the sino-atrial node and its arterial supply were initiated. The surgical modifications included changing the site of the superior vena cava (SVC) cannulation away from the SVC-right atrial junction, incision into the right atrial wall anterior to the sulcus terminalis, and sewing of the superior part of the baffle patch away from the sino-atrial node area. A significant decrease in the incidence of dysrhythmias occurred in the group of patients operated upon after the surgical modifications. The modifications in surgical technique have reduced but not avoided dysrhythmias."} {"id": "PMID:1260983", "title": "Effects of vasodilator therapy for severe pump failure in acute myocardial infarction on short-term and late prognosis.", "content": "Forty-three patients with severe pump failure complicating acute myocardial infarction were treated with vasodilators (nitroprusside (40) and phentolamine (3)) for four hours to 27 days. Cardiac index, stroke volume index, and stroke work index (SWI) increased while the left ventricular filling pressure (LVFP) decreased during vasodilator therapy. Twenty-four of the 43 patients (56%) survived. Of patients with initial SWI between 11-20 gm-m/m2 and LVFP less than 15 mm Hg, 68% survived. In contrast only 18% of patients with SWI of 10 gm-m/m2 or less and LVFP greater than 15 mm Hg survived. Of the 17 patients with clinical shock, 8 (47%) survived. All 24 patients discharged from the hospital were followed for at least 12 months. Fourteen patients died one to 25 months (average 9.2 months) after discharge and the cause of death was pump failure in ten of them (71%). The ten survivors at last follow-up had been followed for 15 to 32 months (average 24 months). The cumulative survival at 24 months was 28%. Thus, despite improvement in short-term prognosis with vasodilator therapy in patients with severe pump failure complicating acute myocardial infarction, the prognosis for long term survival remains unfavorable, possibly due to severe intrinsic cardiac damage.", "contents": "Effects of vasodilator therapy for severe pump failure in acute myocardial infarction on short-term and late prognosis. Forty-three patients with severe pump failure complicating acute myocardial infarction were treated with vasodilators (nitroprusside (40) and phentolamine (3)) for four hours to 27 days. Cardiac index, stroke volume index, and stroke work index (SWI) increased while the left ventricular filling pressure (LVFP) decreased during vasodilator therapy. Twenty-four of the 43 patients (56%) survived. Of patients with initial SWI between 11-20 gm-m/m2 and LVFP less than 15 mm Hg, 68% survived. In contrast only 18% of patients with SWI of 10 gm-m/m2 or less and LVFP greater than 15 mm Hg survived. Of the 17 patients with clinical shock, 8 (47%) survived. All 24 patients discharged from the hospital were followed for at least 12 months. Fourteen patients died one to 25 months (average 9.2 months) after discharge and the cause of death was pump failure in ten of them (71%). The ten survivors at last follow-up had been followed for 15 to 32 months (average 24 months). The cumulative survival at 24 months was 28%. Thus, despite improvement in short-term prognosis with vasodilator therapy in patients with severe pump failure complicating acute myocardial infarction, the prognosis for long term survival remains unfavorable, possibly due to severe intrinsic cardiac damage."} {"id": "PMID:1260984", "title": "Left ventricular function and adrenergic hyperactivity before and after saphenous vein bypass.", "content": "Forty patients with severe angina pectoris were studied before and two weeks after saphenous vein bypass surgery (SVG) in order to assess the effect of this operation on left ventricular performance as judged by systolic time intervals (STI). The patients were divided into two groups: group I included 29 patients in whom no postoperative infarction occurred and group II was composed of 11 patients with postoperative infarction. For group I the PEP/LVET was 0.39 +/- 0.01 preop and slightly but significantly increased at 0.42 +/- 0.004 (P less than 0.025) two weeks postop. The mean preop PEP/LVET was 0.33 +/- 0.01 for group II and dramatically increased to 0.54 +/- 0.02 (P less than 0.001) after surgery. Another striking abnormally was a marked shortening of electromechanical systole (QS2I), which was uniformly present in the postoperative studies. Follow-up studies in 16 patients and urinary catecholamine determination in five patients suggested excessive adrenergic activity was responsible for the abbreviated QS2I. This phenomenon must be considered when interpreting the results of SVG on left ventricular function.", "contents": "Left ventricular function and adrenergic hyperactivity before and after saphenous vein bypass. Forty patients with severe angina pectoris were studied before and two weeks after saphenous vein bypass surgery (SVG) in order to assess the effect of this operation on left ventricular performance as judged by systolic time intervals (STI). The patients were divided into two groups: group I included 29 patients in whom no postoperative infarction occurred and group II was composed of 11 patients with postoperative infarction. For group I the PEP/LVET was 0.39 +/- 0.01 preop and slightly but significantly increased at 0.42 +/- 0.004 (P less than 0.025) two weeks postop. The mean preop PEP/LVET was 0.33 +/- 0.01 for group II and dramatically increased to 0.54 +/- 0.02 (P less than 0.001) after surgery. Another striking abnormally was a marked shortening of electromechanical systole (QS2I), which was uniformly present in the postoperative studies. Follow-up studies in 16 patients and urinary catecholamine determination in five patients suggested excessive adrenergic activity was responsible for the abbreviated QS2I. This phenomenon must be considered when interpreting the results of SVG on left ventricular function."} {"id": "PMID:1260985", "title": "Regional myocardial perfusion during atrial pacing in patients with coronary artery disease.", "content": "Regional myocardial perfusion (RMP) was measured with 133xenon and a multiple-crystal scintillation camera at rest and during atrial pacing in 24 patients with normal coronary arteriograms or less than 50% lesions, Group I, and in 24 with significant (greater than 50% lesions) left coronary artery disease (CAD), Group II. Pacing induced increases in the double product (DP) of heart rate and systolic blood pressure, an index of myocardial oxygen consumption, were not different for Groups I and II. In Group I average mean LV perfusion rate was subnormal at rest but rose from 49 to 73 ml/100 g-min during pacing to 150/min without angina. A response index (RI), (deltaMP X 10(3)/deltaDP), averaged 2.93. Twenty patients in Group II developed angina during pacing. The average mean LV perfusion rose less than in Group I, from 48 to 64 ml/100 g-min (P less than 0.05) and the average RI, 1.76, was lower (P less than 0.01). In 19 of these patients, average RMP distal to the major coronary lesion increased from 46 to 58 ml/100 g-min; this increase during pacing was significantly less than in the remainder of the LV of 48 to 66 ml/100 g-min (P less than 0.05). Average regional RIs were 1.39 and 2.18, respectively. In three patients the presence of collaterals termed adequate by radiological criteria was not associated with preferential decreases in the distal regional RI. The data support the hypothesis that in some patients with CAD, angina pectoris results when an obstructive coronary lesion restricts the total or regional myocardial blood flow response to an increased rate of myocardial oxygen consumption.", "contents": "Regional myocardial perfusion during atrial pacing in patients with coronary artery disease. Regional myocardial perfusion (RMP) was measured with 133xenon and a multiple-crystal scintillation camera at rest and during atrial pacing in 24 patients with normal coronary arteriograms or less than 50% lesions, Group I, and in 24 with significant (greater than 50% lesions) left coronary artery disease (CAD), Group II. Pacing induced increases in the double product (DP) of heart rate and systolic blood pressure, an index of myocardial oxygen consumption, were not different for Groups I and II. In Group I average mean LV perfusion rate was subnormal at rest but rose from 49 to 73 ml/100 g-min during pacing to 150/min without angina. A response index (RI), (deltaMP X 10(3)/deltaDP), averaged 2.93. Twenty patients in Group II developed angina during pacing. The average mean LV perfusion rose less than in Group I, from 48 to 64 ml/100 g-min (P less than 0.05) and the average RI, 1.76, was lower (P less than 0.01). In 19 of these patients, average RMP distal to the major coronary lesion increased from 46 to 58 ml/100 g-min; this increase during pacing was significantly less than in the remainder of the LV of 48 to 66 ml/100 g-min (P less than 0.05). Average regional RIs were 1.39 and 2.18, respectively. In three patients the presence of collaterals termed adequate by radiological criteria was not associated with preferential decreases in the distal regional RI. The data support the hypothesis that in some patients with CAD, angina pectoris results when an obstructive coronary lesion restricts the total or regional myocardial blood flow response to an increased rate of myocardial oxygen consumption."} {"id": "PMID:1260986", "title": "Influence of dobutamine on regional myocardial blood flow and ventricular performance during acute and chronic myocardial ischemia in dogs.", "content": "The data from this study document that dobutamine is a powerful inotropic agent in anesthetized dogs with acute myocardial ischemia and in awake, unsedated ones with chronic myocardial infarction. Dobutamine significantly increases heart rate at relatively small doses in anesthetized dogs with acute myocardial ischemia but considerably larger amounts of dobutamine are required to significantly increase heart rate in awake, unsedated dogs with myocardial infarction. Dobutamine also significantly increases regional myocardial blood flow to all areas of the heart at 20mug/kg/min in both anesthetized dogs with acute myocardial ischemia and awake, unsedated ones with myocardial infarction. However, in anesthetized dogs 20mug/kg/min of dobutamine significantly increases epicardial ST-segment elevation during acute myocardial ischemia. Propranolol prevents the inotropic and chronotropic effects of dobutamine in both anesthetized and awake, unsedated dogs. This study suggests that during experimental acute myocardial ischemia dobutamine given at doses that significantly increase heart rate and contractility may increase the extent of myocardial damage. The data also suggest that this agent should be of value in the setting of severe myocardial depression without associated severe coronary artery disease to increase cardiac contractility at doses that do not markedly alter heart rate. The hemodynamic and coronary blood flow effects of dobutamine in patients with and without severe coronary artery disease should be evaluated.", "contents": "Influence of dobutamine on regional myocardial blood flow and ventricular performance during acute and chronic myocardial ischemia in dogs. The data from this study document that dobutamine is a powerful inotropic agent in anesthetized dogs with acute myocardial ischemia and in awake, unsedated ones with chronic myocardial infarction. Dobutamine significantly increases heart rate at relatively small doses in anesthetized dogs with acute myocardial ischemia but considerably larger amounts of dobutamine are required to significantly increase heart rate in awake, unsedated dogs with myocardial infarction. Dobutamine also significantly increases regional myocardial blood flow to all areas of the heart at 20mug/kg/min in both anesthetized dogs with acute myocardial ischemia and awake, unsedated ones with myocardial infarction. However, in anesthetized dogs 20mug/kg/min of dobutamine significantly increases epicardial ST-segment elevation during acute myocardial ischemia. Propranolol prevents the inotropic and chronotropic effects of dobutamine in both anesthetized and awake, unsedated dogs. This study suggests that during experimental acute myocardial ischemia dobutamine given at doses that significantly increase heart rate and contractility may increase the extent of myocardial damage. The data also suggest that this agent should be of value in the setting of severe myocardial depression without associated severe coronary artery disease to increase cardiac contractility at doses that do not markedly alter heart rate. The hemodynamic and coronary blood flow effects of dobutamine in patients with and without severe coronary artery disease should be evaluated."} {"id": "PMID:1260987", "title": "Effects of isometric exercise on the end-diastolic pressure, volumes, and function of the left ventricle in man.", "content": "Changes induced in left ventricular (LV) hemodynamics by isometric exercise were analyzed in 43 patients: 30 with coronary heart disease (CAD), four with noncoronary heart disease, nine normal. Volumes were angiographically determined and correlated with left ventricular end-diastolic pressure (LVEDP) both at rest and during the fifth minute of 30% sustained handgrip (HNG). All normals and eight with CAD improved LV function during HNG. LVEDP decreased or remained constant, end-diastolic volume (EDV) decreased, end-systolic volume (ESV) decreased, as ejection fraction (EF) remained constant. None of these eight CAD cases altered their regional LV contraction pattern during HNG. Twenty-five patients, 21 CAD and four nonCAD, showed diminished LV function during HNG. LVEDP increased, EDV decreased, ESV increased, as EF declined. In these 21 CAD patients, at least one major coronary vessel was narrowed 70% or more and, with but two exceptions, was not supported by adequate collaterals. In 18, new asynergic zones developed in previously normally contracting areas or pre-existing asynergic zones extended during HNG.", "contents": "Effects of isometric exercise on the end-diastolic pressure, volumes, and function of the left ventricle in man. Changes induced in left ventricular (LV) hemodynamics by isometric exercise were analyzed in 43 patients: 30 with coronary heart disease (CAD), four with noncoronary heart disease, nine normal. Volumes were angiographically determined and correlated with left ventricular end-diastolic pressure (LVEDP) both at rest and during the fifth minute of 30% sustained handgrip (HNG). All normals and eight with CAD improved LV function during HNG. LVEDP decreased or remained constant, end-diastolic volume (EDV) decreased, end-systolic volume (ESV) decreased, as ejection fraction (EF) remained constant. None of these eight CAD cases altered their regional LV contraction pattern during HNG. Twenty-five patients, 21 CAD and four nonCAD, showed diminished LV function during HNG. LVEDP increased, EDV decreased, ESV increased, as EF declined. In these 21 CAD patients, at least one major coronary vessel was narrowed 70% or more and, with but two exceptions, was not supported by adequate collaterals. In 18, new asynergic zones developed in previously normally contracting areas or pre-existing asynergic zones extended during HNG."} {"id": "PMID:1260988", "title": "Myocardial reperfusion in acute experimental ischemia. Beneficial effects of prior treatment with steroids.", "content": "To test the hypothesis that prior steroid administration may enhance the mechanical and metabolic response to myocardial reperfusion, regional myocardial function (Hg-in-silastic length gauges), transmyocardial lactate balance and K+ difference were measured in 12 control and 13 treated (30 mg/kg methyl-prednisolone, 30 to 60 min postocclusion) dogs. At three hours of ischemia, systolic shortening in the ischemic segment was greater in treated dogs (40.6% vs. 12%, P less than 0.05), while both lactate balance and K+ arteriovenous difference became positive. Lactate balance and K+ difference remained negative in the untreated animals. After three hours of occlusion and one hour of reperfusion, recovery of shortening was significantly greater in the treated animals (75.9 vs. 31.6%, P less than 0.05). In addition, while lactate balance remained negative among the control dogs, it further improved in the treated dogs. Thus, steroid administration during experimental coronary occlusion impedes the progression of ischemia and is additive to reperfusion in reversing ischemic dysfunction.", "contents": "Myocardial reperfusion in acute experimental ischemia. Beneficial effects of prior treatment with steroids. To test the hypothesis that prior steroid administration may enhance the mechanical and metabolic response to myocardial reperfusion, regional myocardial function (Hg-in-silastic length gauges), transmyocardial lactate balance and K+ difference were measured in 12 control and 13 treated (30 mg/kg methyl-prednisolone, 30 to 60 min postocclusion) dogs. At three hours of ischemia, systolic shortening in the ischemic segment was greater in treated dogs (40.6% vs. 12%, P less than 0.05), while both lactate balance and K+ arteriovenous difference became positive. Lactate balance and K+ difference remained negative in the untreated animals. After three hours of occlusion and one hour of reperfusion, recovery of shortening was significantly greater in the treated animals (75.9 vs. 31.6%, P less than 0.05). In addition, while lactate balance remained negative among the control dogs, it further improved in the treated dogs. Thus, steroid administration during experimental coronary occlusion impedes the progression of ischemia and is additive to reperfusion in reversing ischemic dysfunction."} {"id": "PMID:1260989", "title": "Effect of intra-aortic balloon counterpulsation on the motion and perfusion of acutely ischemic myocardium. An experimental echocardiographic study.", "content": "The effect of intra-aortic balloon counterpulsation (IABC) on the motion and perfusion of ischemic left ventricular posterior myocardium was studied in 30 open-chest dogs, using ultrasound to register motion and 7-10 mu radioactive microspheres to determine perfusion. Circumflex coronary artery ligation produced acute aneurysmal bulging during isovolumetric contraction and diminished ischemic wall velocity during systolic ejection. Myocardial perfusion was determined in five dogs; perfusion of the area supplied by the ligated coronary artery fell from a control value of 72.9 +/- 13.8 (SE) to 30.0 +/- 2.3 cc/100 g/min (P less than 0.05) at 5 minutes after coronary occlusion. IABC was then administered for one hour, with a fall in aortic systolic pressure (112 +/- 6 to 105 +/- 7 mm Hg, P less than 0.05) and rise in peak aortic diastolic pressure (94 +/- 6 to 102 +/- 7 mm Hg, P less than 0.05). Despite this the ischemic area showed no change in perfusion (measured at the same time): 30.0 +/- 2.3 to 28.0 +/- 2.4 cc/100 g/min. Little change in wall motion occurred: aneurysmal bulging decreased modestly (4.5 +/- 0.3 to 3.6 +/- 0.3 mm, P less than 0.05), but ischemic wall velocity did not increase. After cessation of counterpulsation and one hour of coronary reperfusion aneurysmal bulging disappeared and wall velocity improved. The addition of norepinephrine (eight dogs) or nitroprusside (seven dogs) to intraaortic balloon counterpulsation did not cause a significant further improvement in the response of the dyskinesis during the period of ischemia. We conclude that IABC has little effect on ischemic dyskinesis, probably due to its failure to improve perfusion of the acutely ischemic myocardium.", "contents": "Effect of intra-aortic balloon counterpulsation on the motion and perfusion of acutely ischemic myocardium. An experimental echocardiographic study. The effect of intra-aortic balloon counterpulsation (IABC) on the motion and perfusion of ischemic left ventricular posterior myocardium was studied in 30 open-chest dogs, using ultrasound to register motion and 7-10 mu radioactive microspheres to determine perfusion. Circumflex coronary artery ligation produced acute aneurysmal bulging during isovolumetric contraction and diminished ischemic wall velocity during systolic ejection. Myocardial perfusion was determined in five dogs; perfusion of the area supplied by the ligated coronary artery fell from a control value of 72.9 +/- 13.8 (SE) to 30.0 +/- 2.3 cc/100 g/min (P less than 0.05) at 5 minutes after coronary occlusion. IABC was then administered for one hour, with a fall in aortic systolic pressure (112 +/- 6 to 105 +/- 7 mm Hg, P less than 0.05) and rise in peak aortic diastolic pressure (94 +/- 6 to 102 +/- 7 mm Hg, P less than 0.05). Despite this the ischemic area showed no change in perfusion (measured at the same time): 30.0 +/- 2.3 to 28.0 +/- 2.4 cc/100 g/min. Little change in wall motion occurred: aneurysmal bulging decreased modestly (4.5 +/- 0.3 to 3.6 +/- 0.3 mm, P less than 0.05), but ischemic wall velocity did not increase. After cessation of counterpulsation and one hour of coronary reperfusion aneurysmal bulging disappeared and wall velocity improved. The addition of norepinephrine (eight dogs) or nitroprusside (seven dogs) to intraaortic balloon counterpulsation did not cause a significant further improvement in the response of the dyskinesis during the period of ischemia. We conclude that IABC has little effect on ischemic dyskinesis, probably due to its failure to improve perfusion of the acutely ischemic myocardium."} {"id": "PMID:1260990", "title": "Echocardiographic assessment of left ventricular function in aortic valve disease.", "content": "Echocardiography was used to study left ventricular size and contraction in 128 patients with isolated aortic valve disease -45 patients with aortic stenosis, 25 with mixed aortic valve disease and 58 with aortic regurgitation. Left ventricular measurements included the end-diastolic internal dimension (LVIDd), mural thickness (PWTd), an index of circumferential myocardial contraction-fractional shortening (FS=[(LVIDd-LVIDs)/LVIDd] X 100)--and stroke volume (LVSV). In the absence of left ventricular failure, measurements in aortic stenosis were characteristic of pressure overload with normal LVIDd and FS and an increase in PWTd related to the severity of stenosis; in aortic regurgitation, there was volume overload with increases in LVIDd and PWTd which were related to the severity of regurgitation, while FS was slightly reduced. In mixed aortic valve disease there was evidence of both pressure and volume overload. When left ventricular failure was associated with aortic stenosis, mixed aortic valve disease and chronic aortic regurgitation, FS was usually reduced. By contrast, in a recent patient with acute severe aortic regurgitation, FS was normal despite left ventricular failure, suggesting pump rather than myocardial failure.", "contents": "Echocardiographic assessment of left ventricular function in aortic valve disease. Echocardiography was used to study left ventricular size and contraction in 128 patients with isolated aortic valve disease -45 patients with aortic stenosis, 25 with mixed aortic valve disease and 58 with aortic regurgitation. Left ventricular measurements included the end-diastolic internal dimension (LVIDd), mural thickness (PWTd), an index of circumferential myocardial contraction-fractional shortening (FS=[(LVIDd-LVIDs)/LVIDd] X 100)--and stroke volume (LVSV). In the absence of left ventricular failure, measurements in aortic stenosis were characteristic of pressure overload with normal LVIDd and FS and an increase in PWTd related to the severity of stenosis; in aortic regurgitation, there was volume overload with increases in LVIDd and PWTd which were related to the severity of regurgitation, while FS was slightly reduced. In mixed aortic valve disease there was evidence of both pressure and volume overload. When left ventricular failure was associated with aortic stenosis, mixed aortic valve disease and chronic aortic regurgitation, FS was usually reduced. By contrast, in a recent patient with acute severe aortic regurgitation, FS was normal despite left ventricular failure, suggesting pump rather than myocardial failure."} {"id": "PMID:1260991", "title": "Echocardiographic assessment of left ventricular function in mitral valve disease.", "content": "Echocardiography was used to study left ventricular size and contraction in 90 patients with isolated mitral valve disease--47 patients with mitral stenosis, 26 with mixed mitral valve disease and 89 with mitral regurgitation. Left ventricular measurements included the end-diastolic internal dimension (LVIDd), mural thickness (PWTd), an index of circumferential myocardial contraction--fractional shortening (see article)--and stroke volume (LVSV). The left ventricle was abnormally small only when mitral stenosis was severe. Reduced myocardial contraction was common in patients with rheumatic valvular heart disease but was rarely severe. In mitral regurgitation without left ventricular failure, measurements were characteristic of volume overload with increases in LVIDd, LVSV and PWTd which were related to the severity of regurgitation. In other diseases, left ventricular failure is usually associated with reduced myocardial contraction (FS) but in mitral regurgitation with failure, myocardial contraction (FS 32%) did not differ significantly from normal (34%). The reduction in afterload caused by mitral regurgitation probably increases myocardial contraction and may lead to underestimation of the severity of myocardial impairment. Also potentially misleading was severe mitral regurgitation with normal values for LVIDd and LVSV (three patients). When the distinction between cardiomyopathy with secondary mitral regurgitation and primary mitral regurgitation was difficult clinically, echocardiography could usually make the distinction by demonstrating severe reduction of myocardial contraction with a slight or moderate increase in LVSV.", "contents": "Echocardiographic assessment of left ventricular function in mitral valve disease. Echocardiography was used to study left ventricular size and contraction in 90 patients with isolated mitral valve disease--47 patients with mitral stenosis, 26 with mixed mitral valve disease and 89 with mitral regurgitation. Left ventricular measurements included the end-diastolic internal dimension (LVIDd), mural thickness (PWTd), an index of circumferential myocardial contraction--fractional shortening (see article)--and stroke volume (LVSV). The left ventricle was abnormally small only when mitral stenosis was severe. Reduced myocardial contraction was common in patients with rheumatic valvular heart disease but was rarely severe. In mitral regurgitation without left ventricular failure, measurements were characteristic of volume overload with increases in LVIDd, LVSV and PWTd which were related to the severity of regurgitation. In other diseases, left ventricular failure is usually associated with reduced myocardial contraction (FS) but in mitral regurgitation with failure, myocardial contraction (FS 32%) did not differ significantly from normal (34%). The reduction in afterload caused by mitral regurgitation probably increases myocardial contraction and may lead to underestimation of the severity of myocardial impairment. Also potentially misleading was severe mitral regurgitation with normal values for LVIDd and LVSV (three patients). When the distinction between cardiomyopathy with secondary mitral regurgitation and primary mitral regurgitation was difficult clinically, echocardiography could usually make the distinction by demonstrating severe reduction of myocardial contraction with a slight or moderate increase in LVSV."} {"id": "PMID:1260992", "title": "The determinants of onset of mitral valve prolapse in the systolic click-late systolic murmur syndrome.", "content": "The onset of mitral valve prolapse and its close correlate, the time of systolic click, vary considerably with different physiologic and pharmacologic interventions. In order to explain the mechanism responsible for these alterations, the effects of tilt and amyl nitrite inhalation on left ventricular dynamics and the time of the systolic click were studied by analyzing echocardiograms and simultaneously recorded phonocardiograms in 14 patients with mitral valve prolapse and mid-systolic click. The patients were studied in the supine position, with 40-60 degrees head-up tilt and after amyl nitrite inhalation. Computer analysis of the recordings was used to measure the left ventricular end-diastolic diameter, the click diameter (left ventricular diameter at the time of mid-systolic click), the maximal velocity of circumferential fiber shortening (max VCF), and the time interval between the first heart sound and systolic click (S1-X). With tilt and amyl nitrite, shortening of the S1-X interval b y an average of 44 and 87 msec, respectively, was observed. The click diameter, however, remained virtually constant with both maneuvers. Earlier prolapse after tilt was due to a decrease in the end-diastolic diameter from 5.03 +/- 0.74 to 4.50 +/- 0.68 cm (P less than 0.001) with no change in max VCF. Immediately after amyl nitrite, earlier prolapse was due to an increase of VCF in the preprolapse period, with max VCF increasing from 2.15 +/- 0.27 to 3.06 +/- 0.40 circ/sec (P less than 0.001), there being no change in the end-diastolic diameter up to this time. The constant click diameter indicates that the abnormal valve motion in this syndrome occurs at a critical left ventricular chamber size. Variations in the onset of prolapse are caused by changes in left ventricular end-diastolic dimensions and the velocity of circumferential fiber shortening in the preprolapse period.", "contents": "The determinants of onset of mitral valve prolapse in the systolic click-late systolic murmur syndrome. The onset of mitral valve prolapse and its close correlate, the time of systolic click, vary considerably with different physiologic and pharmacologic interventions. In order to explain the mechanism responsible for these alterations, the effects of tilt and amyl nitrite inhalation on left ventricular dynamics and the time of the systolic click were studied by analyzing echocardiograms and simultaneously recorded phonocardiograms in 14 patients with mitral valve prolapse and mid-systolic click. The patients were studied in the supine position, with 40-60 degrees head-up tilt and after amyl nitrite inhalation. Computer analysis of the recordings was used to measure the left ventricular end-diastolic diameter, the click diameter (left ventricular diameter at the time of mid-systolic click), the maximal velocity of circumferential fiber shortening (max VCF), and the time interval between the first heart sound and systolic click (S1-X). With tilt and amyl nitrite, shortening of the S1-X interval b y an average of 44 and 87 msec, respectively, was observed. The click diameter, however, remained virtually constant with both maneuvers. Earlier prolapse after tilt was due to a decrease in the end-diastolic diameter from 5.03 +/- 0.74 to 4.50 +/- 0.68 cm (P less than 0.001) with no change in max VCF. Immediately after amyl nitrite, earlier prolapse was due to an increase of VCF in the preprolapse period, with max VCF increasing from 2.15 +/- 0.27 to 3.06 +/- 0.40 circ/sec (P less than 0.001), there being no change in the end-diastolic diameter up to this time. The constant click diameter indicates that the abnormal valve motion in this syndrome occurs at a critical left ventricular chamber size. Variations in the onset of prolapse are caused by changes in left ventricular end-diastolic dimensions and the velocity of circumferential fiber shortening in the preprolapse period."} {"id": "PMID:1260993", "title": "Hemodynamic consequences of afterload reduction in patients with chronic aortic regurgitation.", "content": "Nitroprusside was used to reduce afterload in 13 patients with isolated, severe aortic regurgitation. The drug significantly lowered mean aortic pressure, pulse pressure, left ventricular end-diastolic pressure and left ventricular volume. Total ventricular, or angiographic, cardiac index was generally unaffected, but forward cardiac index was improved significantly in 8 of 13 patients. Augmentation of forward cardiac index was seen in patients with subnormal resting forward cardiac index, in patients with decidedly elevated end-diastolic pressure, and in those with depressed resting ejection fractions. Regurgitant fraction fell with nitroprusside in six patients and remained unchanged in seven. Total stroke work index was diminished in all patients. These data show that afterload reduction in patients with severe aortic regurgitation may improve hemodynamics by reducing aortic regurgitation or by improving ventricular pump function. The lowered total stroke work, reduced ventricular size and improved forward cardiac index imply that afterload reduction may benefit left ventricular failure and delay progressive ventricular dysfunction in patients with aortic regurgitation.", "contents": "Hemodynamic consequences of afterload reduction in patients with chronic aortic regurgitation. Nitroprusside was used to reduce afterload in 13 patients with isolated, severe aortic regurgitation. The drug significantly lowered mean aortic pressure, pulse pressure, left ventricular end-diastolic pressure and left ventricular volume. Total ventricular, or angiographic, cardiac index was generally unaffected, but forward cardiac index was improved significantly in 8 of 13 patients. Augmentation of forward cardiac index was seen in patients with subnormal resting forward cardiac index, in patients with decidedly elevated end-diastolic pressure, and in those with depressed resting ejection fractions. Regurgitant fraction fell with nitroprusside in six patients and remained unchanged in seven. Total stroke work index was diminished in all patients. These data show that afterload reduction in patients with severe aortic regurgitation may improve hemodynamics by reducing aortic regurgitation or by improving ventricular pump function. The lowered total stroke work, reduced ventricular size and improved forward cardiac index imply that afterload reduction may benefit left ventricular failure and delay progressive ventricular dysfunction in patients with aortic regurgitation."} {"id": "PMID:1260994", "title": "Right and left ventricular volume characteristics in children with pulmonary stenosis and intact ventricular septum.", "content": "Right (RV) and left ventricular (LV) volume variables were calculated in 27 patients with pulmonary stenosis (PS) during routine cardiac catheterization. These included 21 patients with isolated PS (group I) and seven studies in six patients (group II) with PS and right-to-left atrial shunt. Right and left ventricular volumes were calculated according to Simpson's rule and the area length methods respectively. In group I, right ventricular end-diastolic volume (RVEDV) was not different from normal, RVEF (0.70 +/- 0.02) was significantly higher than normal, and right ventricular stroke index (RVSI) (4.36/L/min/M2 +/- 0.23) was normal. The RVEDV/LVEDV ratio was significantly less than normal (P=0.001). Multiple regression analysis indicated that RVEDV (% of normal) decreased with both age and severity of RV outflow obstruction (r=0.77). In group II, RVEDV and RVSI were both less than normal (P less than 0.001), while RVEF was normal. LVEDV in the group was slightly higher than normal (P=0.026) while LVEF was less than normal (P=0.027) and resulted in normal LVSI. The data suggest that RV and LV function in children with isolated PS are normal, and that knowledge of the RV volume variables is not essential for the management of these patients. In contrast, hearts of patients with PS and right-to-left interatrial shunt have evidence that suggest depressed ventricular function, and the quantitation of RV volume may be helpful in the management of these patients.", "contents": "Right and left ventricular volume characteristics in children with pulmonary stenosis and intact ventricular septum. Right (RV) and left ventricular (LV) volume variables were calculated in 27 patients with pulmonary stenosis (PS) during routine cardiac catheterization. These included 21 patients with isolated PS (group I) and seven studies in six patients (group II) with PS and right-to-left atrial shunt. Right and left ventricular volumes were calculated according to Simpson's rule and the area length methods respectively. In group I, right ventricular end-diastolic volume (RVEDV) was not different from normal, RVEF (0.70 +/- 0.02) was significantly higher than normal, and right ventricular stroke index (RVSI) (4.36/L/min/M2 +/- 0.23) was normal. The RVEDV/LVEDV ratio was significantly less than normal (P=0.001). Multiple regression analysis indicated that RVEDV (% of normal) decreased with both age and severity of RV outflow obstruction (r=0.77). In group II, RVEDV and RVSI were both less than normal (P less than 0.001), while RVEF was normal. LVEDV in the group was slightly higher than normal (P=0.026) while LVEF was less than normal (P=0.027) and resulted in normal LVSI. The data suggest that RV and LV function in children with isolated PS are normal, and that knowledge of the RV volume variables is not essential for the management of these patients. In contrast, hearts of patients with PS and right-to-left interatrial shunt have evidence that suggest depressed ventricular function, and the quantitation of RV volume may be helpful in the management of these patients."} {"id": "PMID:1260995", "title": "The lateral chest film as an unreliable indicator of azygos continuation of the inferior vena cava.", "content": "Recognition of azygos continuation of the inferior vena cava (AC-IVC) is necessary to prevent unnecessary surgery, to modify the approach to right heart catheterization and to avoid potentially fatal azygos ligation at the time of thoracic surgery. Absence of the inferior vena cava (IVC) shadow on the lateral chest film has been claimed to be an important feature of AC-IVC. Our findings, however, indicate that AC-IVC is frequently associated with a normal appearing IVC shadow on lateral chest film study. When the findings on frontal chest film examination suggest AC-IVC, a caval shadow on the lateral view does not exclude the diagnosis. There persists a need for further radiographic evaluation and, if necessary, angiographic confirmation. The lateral chest film does not provide reliable evidence for or against the diagnosis of azygos continuation of the inferior vena cava.", "contents": "The lateral chest film as an unreliable indicator of azygos continuation of the inferior vena cava. Recognition of azygos continuation of the inferior vena cava (AC-IVC) is necessary to prevent unnecessary surgery, to modify the approach to right heart catheterization and to avoid potentially fatal azygos ligation at the time of thoracic surgery. Absence of the inferior vena cava (IVC) shadow on the lateral chest film has been claimed to be an important feature of AC-IVC. Our findings, however, indicate that AC-IVC is frequently associated with a normal appearing IVC shadow on lateral chest film study. When the findings on frontal chest film examination suggest AC-IVC, a caval shadow on the lateral view does not exclude the diagnosis. There persists a need for further radiographic evaluation and, if necessary, angiographic confirmation. The lateral chest film does not provide reliable evidence for or against the diagnosis of azygos continuation of the inferior vena cava."} {"id": "PMID:1260996", "title": "Uremic pericarditis as a cause of cardiac tamponade.", "content": "Uremic pericarditis may complicate either acute or, more commonly, chronic renal failure. When dialysis is not employed, uremic pericarditis is usually a preterminal event and is characterized by a serofibrinous exudation of an amount inadequate to cause cardiac tamponade. Nevertheless, cardiac tamponade may uncommonly be observed in nondialyzed patients. Cardiac tamponade, which may be life-threatening, is more common in dialyzed than in nondialyzed patients with chronic renal failure. The primary causes of cardiac tamponade in uremic pericarditis in order of decreasing frequency are (1) pericardial effusion, usually of the serosanguineous type, (2) massive hemorrhage into the pericardial sac and (3) collagenization of pericardial exudate. From pathologic evidence, the following forms of therapy appear appropriate to manage uremic pericarditis that has reached the stage of causing cardiac tamponade. For effusion, pericardiocentesis or parietal pericardiectomy are logical procedures. Massive hemorrhage into the pericardial sac is usually attended by clotting and requires pericardiotomy and evacuation of clot. Collagenization of exudate yields an encasing, fibrous shell over the heart and requires decortication, as is practised in classical constrictive pericarditis.", "contents": "Uremic pericarditis as a cause of cardiac tamponade. Uremic pericarditis may complicate either acute or, more commonly, chronic renal failure. When dialysis is not employed, uremic pericarditis is usually a preterminal event and is characterized by a serofibrinous exudation of an amount inadequate to cause cardiac tamponade. Nevertheless, cardiac tamponade may uncommonly be observed in nondialyzed patients. Cardiac tamponade, which may be life-threatening, is more common in dialyzed than in nondialyzed patients with chronic renal failure. The primary causes of cardiac tamponade in uremic pericarditis in order of decreasing frequency are (1) pericardial effusion, usually of the serosanguineous type, (2) massive hemorrhage into the pericardial sac and (3) collagenization of pericardial exudate. From pathologic evidence, the following forms of therapy appear appropriate to manage uremic pericarditis that has reached the stage of causing cardiac tamponade. For effusion, pericardiocentesis or parietal pericardiectomy are logical procedures. Massive hemorrhage into the pericardial sac is usually attended by clotting and requires pericardiotomy and evacuation of clot. Collagenization of exudate yields an encasing, fibrous shell over the heart and requires decortication, as is practised in classical constrictive pericarditis."} {"id": "PMID:1260997", "title": "Re-entry due to manifest and concealed. His bundle ectopic systoles. Report of a case.", "content": "Concealed (C) His bundle ectopic systoles (H') have been shown in man to give rise to first and second degree atrioventricular (A-V) block and to simulate nonconducted atrial premature beats (P'). This report outlines a hitherto undescribed electrophysiologic consequence of H' in a 69-year-old man with arteriosclerotic heart disease and a Wenckebach type second degree A-V block in the His-Purkinje system. During a His bundle study, H' were shown to conduct either to the atria and ventricles with varying relationships to P' and QRS, or to conduct only to the atria, simulating nonconducted P' or atrial fusion beats. Both types of H' could initiate a re-entrant arrhythmia during retrograde conduction. Of particular interest are late coupled H' that failed to conduct to the ventricles and also failed to activate the atria because of prior capture by the sinus impulse (CH'). These CH' could also initiate re-entry by conducting retrogradely to engage the subatrial re-entry circuit. Evidence is presented to suggest re-entry occurs by way of a retrograde concealed accessory pathway and antegrade conduction in the atrioventricular node.", "contents": "Re-entry due to manifest and concealed. His bundle ectopic systoles. Report of a case. Concealed (C) His bundle ectopic systoles (H') have been shown in man to give rise to first and second degree atrioventricular (A-V) block and to simulate nonconducted atrial premature beats (P'). This report outlines a hitherto undescribed electrophysiologic consequence of H' in a 69-year-old man with arteriosclerotic heart disease and a Wenckebach type second degree A-V block in the His-Purkinje system. During a His bundle study, H' were shown to conduct either to the atria and ventricles with varying relationships to P' and QRS, or to conduct only to the atria, simulating nonconducted P' or atrial fusion beats. Both types of H' could initiate a re-entrant arrhythmia during retrograde conduction. Of particular interest are late coupled H' that failed to conduct to the ventricles and also failed to activate the atria because of prior capture by the sinus impulse (CH'). These CH' could also initiate re-entry by conducting retrogradely to engage the subatrial re-entry circuit. Evidence is presented to suggest re-entry occurs by way of a retrograde concealed accessory pathway and antegrade conduction in the atrioventricular node."} {"id": "PMID:1260998", "title": "Cord-like aortic valve vegetation in bacterial endocarditis. Demonstration by cardiac ultrasonography. Report of a case.", "content": "The ultrasonic features in a case of bacterial endocarditis in which a highly mobile, cord-like vegetation, attached to the noncoronary cusp of the aortic valve, are reported. The echocardiogram demonstrated abnormal echo patterns in the left ventricular outflow tract in diastrole which were continuous with similar echoes in the aortic root. While these findings did not differ from the previously reported manifestations in cases of flailing aortic valve leaflets, the cardiac ultrasonogram distinguished this vegetative growth. Cardiac ultrasonography revealed a cord-like characteristic, showed the movement of the entire growth into the left ventricular outflow tract in diastole and into the aorta in systole, and allowed estimation of the size of the vegetation. We conclude that cardiac ultrasonography can help in differentiating aortic valve leaflet flail and vegetations in endocarditis.", "contents": "Cord-like aortic valve vegetation in bacterial endocarditis. Demonstration by cardiac ultrasonography. Report of a case. The ultrasonic features in a case of bacterial endocarditis in which a highly mobile, cord-like vegetation, attached to the noncoronary cusp of the aortic valve, are reported. The echocardiogram demonstrated abnormal echo patterns in the left ventricular outflow tract in diastrole which were continuous with similar echoes in the aortic root. While these findings did not differ from the previously reported manifestations in cases of flailing aortic valve leaflets, the cardiac ultrasonogram distinguished this vegetative growth. Cardiac ultrasonography revealed a cord-like characteristic, showed the movement of the entire growth into the left ventricular outflow tract in diastole and into the aorta in systole, and allowed estimation of the size of the vegetation. We conclude that cardiac ultrasonography can help in differentiating aortic valve leaflet flail and vegetations in endocarditis."} {"id": "PMID:1260999", "title": "The use of o-dianisidine for serum haptoglobin electrophoresis using cellulose acetate.", "content": "1. Due to the carcinogenicity of benzidine, a method by which o-dianisidine is used to stain serum haptoglobin is described. Serum haptoglobin is determined by electrophoresis using cellulose acetate as the medium. 2. A comparison of the two staining systems demonstrates good agreement. 0-Dianisidine can be substituted for benzidine without loss of specificity.", "contents": "The use of o-dianisidine for serum haptoglobin electrophoresis using cellulose acetate. 1. Due to the carcinogenicity of benzidine, a method by which o-dianisidine is used to stain serum haptoglobin is described. Serum haptoglobin is determined by electrophoresis using cellulose acetate as the medium. 2. A comparison of the two staining systems demonstrates good agreement. 0-Dianisidine can be substituted for benzidine without loss of specificity."} {"id": "PMID:1261000", "title": "A modified procedure for determining metanephrines in urine.", "content": "We have modified the procedure for determining total metanephrines in urine described by Gupta, Price and Keane(1) to shorten the time necessary for completion while allowing the technician time to perform other tests. The modification involves the extraction of interfering substances from urine. Instead of having to extract 3 individual tubes for each patient, we have developed an extraction that can be performed in a single tube per sample. This allows the number of tubes handled in the first portion of the procedure to be reduced by 66% and a reduction in analysis time of 25%. Day-to-day precision of the method is 8.7%. The modified procedure was compared to the original procedure by running 38 different patients by each method. The mean for the original and modified method were 1.1 mg/24h and 1.1 mg/24h respectively. The correlation coefficient was 0.9051. The t-test (p = 0.05) indicated that there was no significant difference in the means of the methods and the F-test (p = 0.05) indicated that there was no significant difference in the precision of the methods.", "contents": "A modified procedure for determining metanephrines in urine. We have modified the procedure for determining total metanephrines in urine described by Gupta, Price and Keane(1) to shorten the time necessary for completion while allowing the technician time to perform other tests. The modification involves the extraction of interfering substances from urine. Instead of having to extract 3 individual tubes for each patient, we have developed an extraction that can be performed in a single tube per sample. This allows the number of tubes handled in the first portion of the procedure to be reduced by 66% and a reduction in analysis time of 25%. Day-to-day precision of the method is 8.7%. The modified procedure was compared to the original procedure by running 38 different patients by each method. The mean for the original and modified method were 1.1 mg/24h and 1.1 mg/24h respectively. The correlation coefficient was 0.9051. The t-test (p = 0.05) indicated that there was no significant difference in the means of the methods and the F-test (p = 0.05) indicated that there was no significant difference in the precision of the methods."} {"id": "PMID:1261001", "title": "Future education and training requirements of clinical biochemists.", "content": "In order for clinical chemistry to attain full stature as a profession, and clinical biochemistry to become front rank as a discipline, the future education and training of clinical biochemists will require (i) that we achieve recognition and support from our Universities and Hospitals and, where possible, the establishment of Chairs in Clinical Biochemistry, (ii) that we have the resources to attract appropriately qualified physicians and scientists to the staff, (iii) that good courses are developed on the \"bio-chemistry of human diseases\", \"analytical clinical chemistry\" and \"laboratory administration and management\", as a minumum, (iv) that we have the capacity to attract good students for graduate research experience and postgraduate students (both MD and PhD) for professional training and (v) that funds are made available to support these students.", "contents": "Future education and training requirements of clinical biochemists. In order for clinical chemistry to attain full stature as a profession, and clinical biochemistry to become front rank as a discipline, the future education and training of clinical biochemists will require (i) that we achieve recognition and support from our Universities and Hospitals and, where possible, the establishment of Chairs in Clinical Biochemistry, (ii) that we have the resources to attract appropriately qualified physicians and scientists to the staff, (iii) that good courses are developed on the \"bio-chemistry of human diseases\", \"analytical clinical chemistry\" and \"laboratory administration and management\", as a minumum, (iv) that we have the capacity to attract good students for graduate research experience and postgraduate students (both MD and PhD) for professional training and (v) that funds are made available to support these students."} {"id": "PMID:1261002", "title": "Comparison of serum gastrin radioimmunoassay kits.", "content": "1. Two commercially available kit procedures for gastrin measurement were investigated. 2. While the precision of both kits appeared comparable, discrepancies were observed in both accuracy and parallel studies and in the comparison of kit standards and patients' samples.", "contents": "Comparison of serum gastrin radioimmunoassay kits. 1. Two commercially available kit procedures for gastrin measurement were investigated. 2. While the precision of both kits appeared comparable, discrepancies were observed in both accuracy and parallel studies and in the comparison of kit standards and patients' samples."} {"id": "PMID:1261003", "title": "The reduction of oxo-acids by human tissue extracts.", "content": "The reduction of pyruvate, 2-oxobutyrate, hydroxy-pyruvate and glyoxylate under optimal conditions at 37 degrees by extracts of human heart, kidney, pancreas, skeletal muscle and liver has been examined. The ratios of reduction rates, particularly of glyoxylate and 2-oxobutyrate reveal a capacity to differentiate the isoenzyme composition of the tissue extracts.", "contents": "The reduction of oxo-acids by human tissue extracts. The reduction of pyruvate, 2-oxobutyrate, hydroxy-pyruvate and glyoxylate under optimal conditions at 37 degrees by extracts of human heart, kidney, pancreas, skeletal muscle and liver has been examined. The ratios of reduction rates, particularly of glyoxylate and 2-oxobutyrate reveal a capacity to differentiate the isoenzyme composition of the tissue extracts."} {"id": "PMID:1261004", "title": "A new automated procedure for serum inorganic phosphorus.", "content": "1. The method of Parekh and Jung for determination of inorganic phosphorous in serum has been adapted for automation. One of the assets of the method is its unusually stable reagents. The automated procedure is highly accurate, sensitive, rapid and economic. Its other advantages are discussed in light of the literature.", "contents": "A new automated procedure for serum inorganic phosphorus. 1. The method of Parekh and Jung for determination of inorganic phosphorous in serum has been adapted for automation. One of the assets of the method is its unusually stable reagents. The automated procedure is highly accurate, sensitive, rapid and economic. Its other advantages are discussed in light of the literature."} {"id": "PMID:1261005", "title": "Performance of \"kits\" used for clinical chemical analysis of GOT (aspartate aminotransferase).", "content": "Forty-three kits for clinical chemical analysis of GOT (aspartate aminotransferase) were evaluated. The reference method was the kinetic method performed on the Abott ABA-100 Bichromatic Analyzer. Specific data are tabulated for each kit and include ease and speed of testing and performance data. Most kits failed to provide completely adequate labelling information. Reproducibility CV for the kits varied widely (4.20 to 21.26 for the normal pool and 1.57 to 20.51 for the high pool). Many kits gave significant numbers of false positive and false negative results on patient samples. There is a need for manufacturers to either derive their own normal ranges or to establish exact equivalency values with the method used to establish the normal values. No difference was demonstrated between performance by two skilled technologists. However, we did detect lot-to-lot variation and differences in performance between narrow bandpass and wide bandpass spectrophotometers.", "contents": "Performance of \"kits\" used for clinical chemical analysis of GOT (aspartate aminotransferase). Forty-three kits for clinical chemical analysis of GOT (aspartate aminotransferase) were evaluated. The reference method was the kinetic method performed on the Abott ABA-100 Bichromatic Analyzer. Specific data are tabulated for each kit and include ease and speed of testing and performance data. Most kits failed to provide completely adequate labelling information. Reproducibility CV for the kits varied widely (4.20 to 21.26 for the normal pool and 1.57 to 20.51 for the high pool). Many kits gave significant numbers of false positive and false negative results on patient samples. There is a need for manufacturers to either derive their own normal ranges or to establish exact equivalency values with the method used to establish the normal values. No difference was demonstrated between performance by two skilled technologists. However, we did detect lot-to-lot variation and differences in performance between narrow bandpass and wide bandpass spectrophotometers."} {"id": "PMID:1261006", "title": "Bilirubin quantitation with lipemic plasma.", "content": "1. In the presence of lipemia, the estimation of BR by diazo method is variable and hence unreliable. 2. The estimation of BR in lipemic plasma by the use of the A-O bilirubinometer yielded BR levels which were consistently lower than theoretical values. 3. By regression analysis of the percent error in BR estimation, (using the A-O bilirubinometer) and TG Concentrations, a straight line is obtained. Based upon this line, a correction factor for plasma BR concentration in the range of 5-25 mg/dl can be obtained if the degree of lipemia is known.", "contents": "Bilirubin quantitation with lipemic plasma. 1. In the presence of lipemia, the estimation of BR by diazo method is variable and hence unreliable. 2. The estimation of BR in lipemic plasma by the use of the A-O bilirubinometer yielded BR levels which were consistently lower than theoretical values. 3. By regression analysis of the percent error in BR estimation, (using the A-O bilirubinometer) and TG Concentrations, a straight line is obtained. Based upon this line, a correction factor for plasma BR concentration in the range of 5-25 mg/dl can be obtained if the degree of lipemia is known."} {"id": "PMID:1261007", "title": "Triglyceride assay using the ABA-100.", "content": "1. A fast, simple, accurate method for the assay of triglycerides on the ABA-100 is described. 2. The Abbott A-Gent Triglyceride kit, Calbiochem Triglyceride Stat-Pack reagent and the Smith Kline French Eskalab Triglyceride reagent were evaluated for use with this method. The reagents were all found to be satisfactory, but the Abbott A-Gent Triglyceride kit was found to be less stable than the other reagents.", "contents": "Triglyceride assay using the ABA-100. 1. A fast, simple, accurate method for the assay of triglycerides on the ABA-100 is described. 2. The Abbott A-Gent Triglyceride kit, Calbiochem Triglyceride Stat-Pack reagent and the Smith Kline French Eskalab Triglyceride reagent were evaluated for use with this method. The reagents were all found to be satisfactory, but the Abbott A-Gent Triglyceride kit was found to be less stable than the other reagents."} {"id": "PMID:1261008", "title": "Radioimmunoassay of bile acids in serum.", "content": "We developed four radioimmunoassay procedures for the determination of glycine-conjugated bile acids in serum. Antibodies to two primary bile acids, cholylgycine and chenodeoxycholylglycine, and to two secondary bile acids, sulfolithocholylglycine and deoxycholylglycine, were raised in rabbits after the acids were covalently linked to albumin by use of the carbodiimide reaction. Assay sensitivity for each of these bile acids is in the picomole range with the standard curve extending from 10-80 pmol. The concentration of bile acids in serum increased in various states of liver disease and its measurement appears to be an extremely sensitive indicator of liver function.", "contents": "Radioimmunoassay of bile acids in serum. We developed four radioimmunoassay procedures for the determination of glycine-conjugated bile acids in serum. Antibodies to two primary bile acids, cholylgycine and chenodeoxycholylglycine, and to two secondary bile acids, sulfolithocholylglycine and deoxycholylglycine, were raised in rabbits after the acids were covalently linked to albumin by use of the carbodiimide reaction. Assay sensitivity for each of these bile acids is in the picomole range with the standard curve extending from 10-80 pmol. The concentration of bile acids in serum increased in various states of liver disease and its measurement appears to be an extremely sensitive indicator of liver function."} {"id": "PMID:1261009", "title": "Kinetic determination of serum lipase activity with the Abbott ABA-100.", "content": "A turbidimetric procedure for lipase has been adapted for use on the Abbott Bichromatic Analyzer (ABA-100). The method is rapid and results compared well with those by the more traditional method of Cherry and Crandall [Am. J. Physiol. 100, 266 (1932)]. Advantages of this method include shorter incubation time (2 min), smaller sample size (50 mul), neglible interference from bilirubin, and greater dynamic range (to eightfold normal).", "contents": "Kinetic determination of serum lipase activity with the Abbott ABA-100. A turbidimetric procedure for lipase has been adapted for use on the Abbott Bichromatic Analyzer (ABA-100). The method is rapid and results compared well with those by the more traditional method of Cherry and Crandall [Am. J. Physiol. 100, 266 (1932)]. Advantages of this method include shorter incubation time (2 min), smaller sample size (50 mul), neglible interference from bilirubin, and greater dynamic range (to eightfold normal)."} {"id": "PMID:1261010", "title": "Gas-liquid chromatographic profile of neutral and acidic metabolites in cerebrospinal fluid from newborns and infants.", "content": "A profile (chromatographic pattern) of the neutral and acidic metabolites present in cerebrospinal fluid from newborns and infants was obtained by gas-liquid chromatography. The metabolites are those extracted with ethyl acetate and diethyl ether. They are converted to trimethylsilyl ether derivatives, and chromatographed on a column containing 5% silicone OV-101 (methyl) packed on Chromosorb W. Several substances were tentatively identified from their methylene unit values. We established a control profile for infants, and compared profiles for infants and adults. Noteworthy qualitative and quantitative differences from the control were seen for cerebrospinal fluid from subjects with neurological disorders of infections. The technique may be of use in neurological diagnosis.", "contents": "Gas-liquid chromatographic profile of neutral and acidic metabolites in cerebrospinal fluid from newborns and infants. A profile (chromatographic pattern) of the neutral and acidic metabolites present in cerebrospinal fluid from newborns and infants was obtained by gas-liquid chromatography. The metabolites are those extracted with ethyl acetate and diethyl ether. They are converted to trimethylsilyl ether derivatives, and chromatographed on a column containing 5% silicone OV-101 (methyl) packed on Chromosorb W. Several substances were tentatively identified from their methylene unit values. We established a control profile for infants, and compared profiles for infants and adults. Noteworthy qualitative and quantitative differences from the control were seen for cerebrospinal fluid from subjects with neurological disorders of infections. The technique may be of use in neurological diagnosis."} {"id": "PMID:1261011", "title": "Improved determination of prostatic acid phosphatase (sodium thymolphthalein monophosphate substrate).", "content": "We have modified a previously described method for determining acid phosphatase, with thymolphthalein monophosphate as substrate, to increase its sensitivity. We assessed effects of serum on variables influencing acid phosphatase activity as measured by this method. The method is shown to be not completely specific for prostatic acid phosphatase. The importance of standardizing methodology in measurement of enzyme activities is demonstrated.", "contents": "Improved determination of prostatic acid phosphatase (sodium thymolphthalein monophosphate substrate). We have modified a previously described method for determining acid phosphatase, with thymolphthalein monophosphate as substrate, to increase its sensitivity. We assessed effects of serum on variables influencing acid phosphatase activity as measured by this method. The method is shown to be not completely specific for prostatic acid phosphatase. The importance of standardizing methodology in measurement of enzyme activities is demonstrated."} {"id": "PMID:1261013", "title": "The anion gap: its use in quality control.", "content": "Because the anion gap is useful in classifying acid-base disorders, quantitative information on this variable should be readily available. Three populations were studied and means and central 90% ranges were determined for the anion gap, calculated as sodium-(chloride + bicarbonate). In 1047 hospitalized patients the mean was 12 mEq/liter, 86 faster volunteers had a mean of 13 mEq/liter with a 90% range of 9--17 mEq/liter, and 203 plasmaphoresis donors had a mean of 11 mEq/liter with a 90% range of 7--16 mEq/liter. Most of this variability can be accounted for by analytical rather than physiological variation. This quantitation of the anion gap is useful for interchecking electrolyte values as an additional and inexpensive means of laboratory quality control. In 73 of 75 abnormal anion gaps, for which the data were verified to be correct, the clinical information provided a reasonable explanaation for the abnormality.", "contents": "The anion gap: its use in quality control. Because the anion gap is useful in classifying acid-base disorders, quantitative information on this variable should be readily available. Three populations were studied and means and central 90% ranges were determined for the anion gap, calculated as sodium-(chloride + bicarbonate). In 1047 hospitalized patients the mean was 12 mEq/liter, 86 faster volunteers had a mean of 13 mEq/liter with a 90% range of 9--17 mEq/liter, and 203 plasmaphoresis donors had a mean of 11 mEq/liter with a 90% range of 7--16 mEq/liter. Most of this variability can be accounted for by analytical rather than physiological variation. This quantitation of the anion gap is useful for interchecking electrolyte values as an additional and inexpensive means of laboratory quality control. In 73 of 75 abnormal anion gaps, for which the data were verified to be correct, the clinical information provided a reasonable explanaation for the abnormality."} {"id": "PMID:1261014", "title": "Decreased radioassay values for folate after serum extraction when pteroylglutamic acid standards are used.", "content": "Radoiassay values for folate in protein-denautured (extracted) sera are compared with values obtained by individual serum blank correction. Lower folate values are reported for sera extracted at pH 1.3, 7.6, 10.5, and 12.4 when pterolyglutamic acid (PGA) calibration standards are used. The results are unchanged when ascorbate added to the sera is increased from 1 to 20 g/liter and when [3H]PGA is substituted for 125I-labeled PGA. However, a higher mean value for extracted serum is reported when N-5-methyltetrahydrofolic acid calibration standards are substituted for PGA. Because both patients' samples and assay calibrators were subjected to the same extraction methods, our results suggest that serum folate behaves differently from PGA during the extractions.", "contents": "Decreased radioassay values for folate after serum extraction when pteroylglutamic acid standards are used. Radoiassay values for folate in protein-denautured (extracted) sera are compared with values obtained by individual serum blank correction. Lower folate values are reported for sera extracted at pH 1.3, 7.6, 10.5, and 12.4 when pterolyglutamic acid (PGA) calibration standards are used. The results are unchanged when ascorbate added to the sera is increased from 1 to 20 g/liter and when [3H]PGA is substituted for 125I-labeled PGA. However, a higher mean value for extracted serum is reported when N-5-methyltetrahydrofolic acid calibration standards are substituted for PGA. Because both patients' samples and assay calibrators were subjected to the same extraction methods, our results suggest that serum folate behaves differently from PGA during the extractions."} {"id": "PMID:1261015", "title": "Technical pitfalls in measurement of venous plasma NH3 concentration.", "content": "Measurement of venous plasma NH3 in normal subjects by the ion-exchange method of Forman [Clin. Chem. 10, 497 (1964)] in a hospital clinical laboratory gave a mean value of 640 mug/liter (range, 300-1320 mug/liter; intraassay, intra-individual, and inter-individual coefficients of variation, 8, 47, and 47%, respectively). The following conditions adversely affect the reproducibility of the test: pollution of laboratory atmosphere and glassware by NH3-containing detergents; smoking by patient or analyst; delay, turbulence, or use of heparin lock in venipuncture; delay or warming of plasma above degrees C before mixing it with resin; and delay in colorimetric analysis of resin eluate. When these sources of error were eliminated, the mean value for normals was reduced to 330 mug/liter, the range was narrowed to 220-470 mug/liter, and the above-mentioned CV's were 5, 16, and 17%, respectively. With the precautions cited, furthermore, the intra-assay and intra-individual CV's for fasting NH3 concentration in cirrhotic patients were similarly reduced. An NH3 tolerance test was done by administering a standard dose of NH4Cl to patients and measuring venous plasma NH3 at 0, 15, 30, 60, and 90 min; the NH3 tolerance was quantified from the area under the curve relating concentration to time (mug - min/liter). As measured in the clinical laboratory, NH3 tolerance of cirrhotic patients showed intra-assay and intra-individual CV's of 50 to 90%. When the tolerance tests were repeated in the same subjects with the laboratory precautions listed above, these CV's were reduced to 8-15%.", "contents": "Technical pitfalls in measurement of venous plasma NH3 concentration. Measurement of venous plasma NH3 in normal subjects by the ion-exchange method of Forman [Clin. Chem. 10, 497 (1964)] in a hospital clinical laboratory gave a mean value of 640 mug/liter (range, 300-1320 mug/liter; intraassay, intra-individual, and inter-individual coefficients of variation, 8, 47, and 47%, respectively). The following conditions adversely affect the reproducibility of the test: pollution of laboratory atmosphere and glassware by NH3-containing detergents; smoking by patient or analyst; delay, turbulence, or use of heparin lock in venipuncture; delay or warming of plasma above degrees C before mixing it with resin; and delay in colorimetric analysis of resin eluate. When these sources of error were eliminated, the mean value for normals was reduced to 330 mug/liter, the range was narrowed to 220-470 mug/liter, and the above-mentioned CV's were 5, 16, and 17%, respectively. With the precautions cited, furthermore, the intra-assay and intra-individual CV's for fasting NH3 concentration in cirrhotic patients were similarly reduced. An NH3 tolerance test was done by administering a standard dose of NH4Cl to patients and measuring venous plasma NH3 at 0, 15, 30, 60, and 90 min; the NH3 tolerance was quantified from the area under the curve relating concentration to time (mug - min/liter). As measured in the clinical laboratory, NH3 tolerance of cirrhotic patients showed intra-assay and intra-individual CV's of 50 to 90%. When the tolerance tests were repeated in the same subjects with the laboratory precautions listed above, these CV's were reduced to 8-15%."} {"id": "PMID:1261016", "title": "Interference of fatty acids in the competitive protein-binding assay for serum thyroxine.", "content": "An increase in apparent thyroxine values obtained by competitive protein-binding assay on storage of sera is well documented. We find that the major source of this positive bias is probably the unsaturated nonesterified fatty acids. Nonesterified fatty acids cause a positive basis in the competitive protein-binding assay for serum thyroxine because they inhibit the binding of radioactive thyroxine by the serum-binding reagent (probably thyroxine-binding globulin). This inhibition by fatty acids may be due to the formation of a fatty acid/thyroxine complex. The degree of inhibition caused by the fatty acids depends on the length of the carbon chain of the fatty acid and the degree of saturation. Short-chain fatty acids are more potent inhibitors of thyroxine binding than those with a longer chain, and unsaturated fatty acids are more potent inhibitors of thyroxine binding than are saturated fatty acids. The polyunsaturated fatty acid, arachidonic acid, was the most potent inhibitor of all the fatty acids tested. Triglycerides (triacylglycerols) insignificantly inhibit thyroxine binding in this assay.", "contents": "Interference of fatty acids in the competitive protein-binding assay for serum thyroxine. An increase in apparent thyroxine values obtained by competitive protein-binding assay on storage of sera is well documented. We find that the major source of this positive bias is probably the unsaturated nonesterified fatty acids. Nonesterified fatty acids cause a positive basis in the competitive protein-binding assay for serum thyroxine because they inhibit the binding of radioactive thyroxine by the serum-binding reagent (probably thyroxine-binding globulin). This inhibition by fatty acids may be due to the formation of a fatty acid/thyroxine complex. The degree of inhibition caused by the fatty acids depends on the length of the carbon chain of the fatty acid and the degree of saturation. Short-chain fatty acids are more potent inhibitors of thyroxine binding than those with a longer chain, and unsaturated fatty acids are more potent inhibitors of thyroxine binding than are saturated fatty acids. The polyunsaturated fatty acid, arachidonic acid, was the most potent inhibitor of all the fatty acids tested. Triglycerides (triacylglycerols) insignificantly inhibit thyroxine binding in this assay."} {"id": "PMID:1261018", "title": "Specificity and reproducibility of acetone precipitation in identifying surface-active phosphatidylcholine in amniotic fluid.", "content": "We show the thoretical and actual variability in the amount of surface-active lecithin precipitated in the acetone-precipitation step of determining lecithin/sphingomyelin (L/S) ratios in the clinical laboratory. Lecithins precipitated may range from 60 to 90% of the total surface-active lecithins present. The range is sufficient to account for the occasional \"immature\" L/S ratios (less than 2/1) found in amniotic fluid from women bearing mature fetuses.", "contents": "Specificity and reproducibility of acetone precipitation in identifying surface-active phosphatidylcholine in amniotic fluid. We show the thoretical and actual variability in the amount of surface-active lecithin precipitated in the acetone-precipitation step of determining lecithin/sphingomyelin (L/S) ratios in the clinical laboratory. Lecithins precipitated may range from 60 to 90% of the total surface-active lecithins present. The range is sufficient to account for the occasional \"immature\" L/S ratios (less than 2/1) found in amniotic fluid from women bearing mature fetuses."} {"id": "PMID:1261019", "title": "Four commercial urease reagents and a laboratory-prepared reagent compared for analysis of blood urea nitrogen with the Beckman analyzer.", "content": "Three laboratory-prepared urease reagents were compared with a commercial preparation supplied for routine use on the Beckman Blood Urea Nitrogen Analyzer. There were discrepancies in results for urea nitrogen among the four urease reagents when matching serum and the corresponding oxalate/fluoride treated plasma were compared as measured with the Beckman Analyzer and continuous-flow (AutoAnalyzer) method. All four urease preparations were affected by fluoride, but to different extents. We believe that an effective laboratory reagent can be prepared in the laboratory at significantly lower cost.", "contents": "Four commercial urease reagents and a laboratory-prepared reagent compared for analysis of blood urea nitrogen with the Beckman analyzer. Three laboratory-prepared urease reagents were compared with a commercial preparation supplied for routine use on the Beckman Blood Urea Nitrogen Analyzer. There were discrepancies in results for urea nitrogen among the four urease reagents when matching serum and the corresponding oxalate/fluoride treated plasma were compared as measured with the Beckman Analyzer and continuous-flow (AutoAnalyzer) method. All four urease preparations were affected by fluoride, but to different extents. We believe that an effective laboratory reagent can be prepared in the laboratory at significantly lower cost."} {"id": "PMID:1261020", "title": "Use of blood specimens collected on filter paper in screening for abnormal hemoglobins.", "content": "Both cellulose acetate electrophoresis and citrate agar electrophoresis were performed on 834 blood samples collected on filter paper in Jamaica and shipped for testing to the National Hemoglobinopathy Standardization Laboratory at the U.S. National Center for Disease Control. Additionally, 30 blood samples collected locally were stored on filter paper, in microhematocrit capillary tubes, and as whole blood specimens; at selected times the samples were tested for stability to determine the best sample-collection technique for hemoglobin electrophoresis. Results were most nearly accurate when both cellulose acetate electrophoresis and citrate agar testing were used. The methods are easy to perform, but results are unreliable if the blood samples on filter paper are stored at 4 degrees C for longer than two weeks before they are tested.", "contents": "Use of blood specimens collected on filter paper in screening for abnormal hemoglobins. Both cellulose acetate electrophoresis and citrate agar electrophoresis were performed on 834 blood samples collected on filter paper in Jamaica and shipped for testing to the National Hemoglobinopathy Standardization Laboratory at the U.S. National Center for Disease Control. Additionally, 30 blood samples collected locally were stored on filter paper, in microhematocrit capillary tubes, and as whole blood specimens; at selected times the samples were tested for stability to determine the best sample-collection technique for hemoglobin electrophoresis. Results were most nearly accurate when both cellulose acetate electrophoresis and citrate agar testing were used. The methods are easy to perform, but results are unreliable if the blood samples on filter paper are stored at 4 degrees C for longer than two weeks before they are tested."} {"id": "PMID:1261033", "title": "Quantitation of glycine in plasma and urine by chemical ionization mass fragmentography.", "content": "A new technique has been developed for rapid and precise quantitation of glycine in micro samples of biological fluids. Glycine is measured as the n-butyl N-trifluoroacetyl (TAB) derivative by chemical ionization mass fragmentography, using both methane and isobutane as carrier/reagent gases, with the analogous derivative of 2,2-dideuterioglycine added as the internal standard. This technique is also readily applicable, with sensitivity to the femtomole level, to determinations of other amino acids, as, for example, in studies of congenital errors of metabolism.", "contents": "Quantitation of glycine in plasma and urine by chemical ionization mass fragmentography. A new technique has been developed for rapid and precise quantitation of glycine in micro samples of biological fluids. Glycine is measured as the n-butyl N-trifluoroacetyl (TAB) derivative by chemical ionization mass fragmentography, using both methane and isobutane as carrier/reagent gases, with the analogous derivative of 2,2-dideuterioglycine added as the internal standard. This technique is also readily applicable, with sensitivity to the femtomole level, to determinations of other amino acids, as, for example, in studies of congenital errors of metabolism."} {"id": "PMID:1261035", "title": "Purification of thyroxine and triiodothyronine for radioassay with sephadex.", "content": "The use of [125I] thyroxine in the determination of dialysable thyroxine (free T4) places very high demands on the purity of the reagent. Less than 5% dissociated radioactive iodine (as iodide) is enough to influence the results [1]. For this reason several workers have developed methods for the purification of iodo amino acids used in radioassay for thyroid hormones. Two techniques have been used mainly, namely dialysis of incubated tracer-serum mixture [1,2], and adsorption chromatography on dextran gels in strongly basic buffers [3-5]. In this laboratory we have developed an adsorption chromatography method using bovine serum albumin for the separation of [125I] thyroxine from contaminating compounds.", "contents": "Purification of thyroxine and triiodothyronine for radioassay with sephadex. The use of [125I] thyroxine in the determination of dialysable thyroxine (free T4) places very high demands on the purity of the reagent. Less than 5% dissociated radioactive iodine (as iodide) is enough to influence the results [1]. For this reason several workers have developed methods for the purification of iodo amino acids used in radioassay for thyroid hormones. Two techniques have been used mainly, namely dialysis of incubated tracer-serum mixture [1,2], and adsorption chromatography on dextran gels in strongly basic buffers [3-5]. In this laboratory we have developed an adsorption chromatography method using bovine serum albumin for the separation of [125I] thyroxine from contaminating compounds."} {"id": "PMID:1261037", "title": "[Studies on the accuracy and precision of total serum cholesterol in regional interlaboratory trials (author's transl)].", "content": "The between-run precision of the Liebermann-Burchard reaction modified by Watson was, in our laboratory, 2-3%, the within-run coefficient of variation was 1-2%. The between-run precision of the enzymatic test was 3-4%, the within-run coefficient of variation was 3%. The regression analysis of 92 serum specimens from patients was y = -17.31 + 1.04 chi, the coefficient of regression was r = 0.996. Interlaboratory trials of serum cholesterol were studied in the normal and pathological range. Lyophilized samples of serum prepared commercially and from fresh specimens from patients were analysed by the method of Liebermann-Burchard as well as by the enzymatic procedure. Acceptable results estimated by Liebermann-Burchard were obtained in the different laboratories after using a common standard of cholesterol. The coefficient of variation of the enzymatic test in the interlaboratory trial was higher in comparison to the Liebermann-Burchard reaction. Methodological difficulties of the Liebermann-Burchard reaction are discussed and compared with the specific, enzymatic assay.", "contents": "[Studies on the accuracy and precision of total serum cholesterol in regional interlaboratory trials (author's transl)]. The between-run precision of the Liebermann-Burchard reaction modified by Watson was, in our laboratory, 2-3%, the within-run coefficient of variation was 1-2%. The between-run precision of the enzymatic test was 3-4%, the within-run coefficient of variation was 3%. The regression analysis of 92 serum specimens from patients was y = -17.31 + 1.04 chi, the coefficient of regression was r = 0.996. Interlaboratory trials of serum cholesterol were studied in the normal and pathological range. Lyophilized samples of serum prepared commercially and from fresh specimens from patients were analysed by the method of Liebermann-Burchard as well as by the enzymatic procedure. Acceptable results estimated by Liebermann-Burchard were obtained in the different laboratories after using a common standard of cholesterol. The coefficient of variation of the enzymatic test in the interlaboratory trial was higher in comparison to the Liebermann-Burchard reaction. Methodological difficulties of the Liebermann-Burchard reaction are discussed and compared with the specific, enzymatic assay."} {"id": "PMID:1261038", "title": "Stereospecific distribution of fatty acids in human plasma triglycerides.", "content": "Because of a biological difference between both primary hydroxylgroups of glycerol there are three distinct hydroxylgroups esterified with fatty acids in triglycerides. The distribution of fatty acids in the three distinct positions of triglycerides can be investigated by a combination of partial hydrolysis of triglycerides by pancreatic lipase, phosphorylation of the diglycerides formed and the stereospecific action of phospholipase A on phosphatides. Plasma triglycerides from normal and hyperlipemic humans are analysed. Human plasma triglycerides are highly asymmetric. The 1-position contains more than twice as much palmitic acid as the 3-position. Statistically significant differences are found between normal and hyperlipemic humans for palmitic and linoleic acid at the 2-position, and for oleic and linoleic acid at the 3-position.", "contents": "Stereospecific distribution of fatty acids in human plasma triglycerides. Because of a biological difference between both primary hydroxylgroups of glycerol there are three distinct hydroxylgroups esterified with fatty acids in triglycerides. The distribution of fatty acids in the three distinct positions of triglycerides can be investigated by a combination of partial hydrolysis of triglycerides by pancreatic lipase, phosphorylation of the diglycerides formed and the stereospecific action of phospholipase A on phosphatides. Plasma triglycerides from normal and hyperlipemic humans are analysed. Human plasma triglycerides are highly asymmetric. The 1-position contains more than twice as much palmitic acid as the 3-position. Statistically significant differences are found between normal and hyperlipemic humans for palmitic and linoleic acid at the 2-position, and for oleic and linoleic acid at the 3-position."} {"id": "PMID:1261039", "title": "Interference of sodium azide with the quantitation of serum cholesterol: a comparative study.", "content": "Interference of sodium azide (employed widely as a preservative for serum) with six different cholesterol methods and two modified procedures is analyzed and compared. Sodium azide is shown to lower the serum cholesterol values of the iron-cholesterol methods from 5 to 50% at 0.1 g% azide, and from 60 to 95% at 1.0 g% azide concentration, depending on the method employed. This inhibition is independent of serum cholesterol concentration. Increased serum to reagent (v/v) ratio, i.e., increased azide concentration, caused increased depression of serum cholesterol values. Appropriate choice of low serum-to-reagent (v/v) ratio thus decreases the magnitude of the azide interference in the iron-cholesterol reaction to 3-10% for the precipitation procedures, and to 25% for the non-precipitation procedure at 0.1 g% azide concentration in serum.", "contents": "Interference of sodium azide with the quantitation of serum cholesterol: a comparative study. Interference of sodium azide (employed widely as a preservative for serum) with six different cholesterol methods and two modified procedures is analyzed and compared. Sodium azide is shown to lower the serum cholesterol values of the iron-cholesterol methods from 5 to 50% at 0.1 g% azide, and from 60 to 95% at 1.0 g% azide concentration, depending on the method employed. This inhibition is independent of serum cholesterol concentration. Increased serum to reagent (v/v) ratio, i.e., increased azide concentration, caused increased depression of serum cholesterol values. Appropriate choice of low serum-to-reagent (v/v) ratio thus decreases the magnitude of the azide interference in the iron-cholesterol reaction to 3-10% for the precipitation procedures, and to 25% for the non-precipitation procedure at 0.1 g% azide concentration in serum."} {"id": "PMID:1261040", "title": "Continuous in vivo measurement of creatine kinase variations in man during an exercise.", "content": "In order to obtain information concerning the CPK turnover during exercise, we have elaborated a technique to measure its activity continuously in vivo. A colorimetric method has been adapted to total blood. CPK was measured continuously in 5 physically fit athletes exercised on an ergometric bicycle for 30 min. There was practically no increase in enzymatic activity. The starting level was very high, corresponding perhaps to a \"permanent state of enzyme release\"; the exercise was not hard enough because of the fitness of the athletes or the maximal increase did not occur immediately after the exercise.", "contents": "Continuous in vivo measurement of creatine kinase variations in man during an exercise. In order to obtain information concerning the CPK turnover during exercise, we have elaborated a technique to measure its activity continuously in vivo. A colorimetric method has been adapted to total blood. CPK was measured continuously in 5 physically fit athletes exercised on an ergometric bicycle for 30 min. There was practically no increase in enzymatic activity. The starting level was very high, corresponding perhaps to a \"permanent state of enzyme release\"; the exercise was not hard enough because of the fitness of the athletes or the maximal increase did not occur immediately after the exercise."} {"id": "PMID:1261041", "title": "The influence of thyroxine on the serum free triiodothyronine concentration.", "content": "By means of measurement of the serum free triiodothyronine fraction (%FT3) by equilibrium dialysis, the influence of varying serum concentrations of thyroxine (T4) on %FT3 was studied in conditions associated with lack or excess of serum T4 and in serum enrichment with T4 in vitro. The enrichment of pooled serum with T4 caused significant increases of %FT3 with T4 was added to elevate its T4 content between 10 and 25 mug/dl. In 4 subjects with primary hypothyroidism treated with T3 (25 mug once daily for two weeks, twice daily thereafter), progressive increases of serum T3 were observed while their T4, free T4 and T3 fractions remained unchanged. Consequently, the serum free T3 and thyrotropin concentrations became normal after the serum T3 concentrations became hypernormal. When comparisons of the serum thyroid hormone levels were made between 6 subjects with T3 toxicosis and 8 with a usual variety of hyperthyroidism matched for serum T3 concentration, the former sub-group of hyperthyroidism showed significantly lower serum free T3 concentration (0-51 +/- 0.22 ng/dl versus 0.79 +/- 0-21 ng/dl, p less than 0.05). The amount of T4 in serum is considered to affect its free T3 concentration by virtue of sharing serum-binding proteins.", "contents": "The influence of thyroxine on the serum free triiodothyronine concentration. By means of measurement of the serum free triiodothyronine fraction (%FT3) by equilibrium dialysis, the influence of varying serum concentrations of thyroxine (T4) on %FT3 was studied in conditions associated with lack or excess of serum T4 and in serum enrichment with T4 in vitro. The enrichment of pooled serum with T4 caused significant increases of %FT3 with T4 was added to elevate its T4 content between 10 and 25 mug/dl. In 4 subjects with primary hypothyroidism treated with T3 (25 mug once daily for two weeks, twice daily thereafter), progressive increases of serum T3 were observed while their T4, free T4 and T3 fractions remained unchanged. Consequently, the serum free T3 and thyrotropin concentrations became normal after the serum T3 concentrations became hypernormal. When comparisons of the serum thyroid hormone levels were made between 6 subjects with T3 toxicosis and 8 with a usual variety of hyperthyroidism matched for serum T3 concentration, the former sub-group of hyperthyroidism showed significantly lower serum free T3 concentration (0-51 +/- 0.22 ng/dl versus 0.79 +/- 0-21 ng/dl, p less than 0.05). The amount of T4 in serum is considered to affect its free T3 concentration by virtue of sharing serum-binding proteins."} {"id": "PMID:1261042", "title": "On the mechanism of 5-oxoproline overproduction in 5-oxoprolinuria.", "content": "The primary metabolic defect in 5-oxoprolinuria (pyroglutamic aciduria) is the lack of glutathione synthetase. The mechanism of the concomitant overproduction of 5-oxoproline was studied using cell-free extracts of erythrocytes from control individuals and from patients with 5-oxoprolinuria. Such extracts catalyzed the synthesis of 5-oxoproline from L-glutamate. Addition of ATP, Mg ions and alpha-aminobutyrate was needed for optimal activity. The conversion of glutamate to 5-oxoproline occurred in two steps, catalyzed by gamma-glutamyl-cysteine synthetase and gamma-glutamyl cyclotransferase, respectively. Extracts of erythrocytes from control subjects and patients with 5-oxoprolinuria had identical capacity to synthesize 5-oxoproline. The conversion of glutamate to 5-oxoproline was markedly inhibited by reduced glutathione, which exerted its effect on the gamma-glutamyl-cysteine synthetase step. The following mechanism is postulated for the overproduction of 5-oxoproline in 5-oxoprolinuria: the deficiency of glutathione synthetase causes a lack of glutathione which is an essential feed-back inhibitor in the initial step of its biosynthesis. Therefore gamma-glutamyl-cysteine is produced in excessive amounts and it is subsequently converted to 5-oxoproline (and cysteine) by gamma-glutamyl cyclotransferase. This overproduction of 5-oxoproline exceeds the capacity of the 5-oxoprolinase and 5-oxoproline accumulates in body fluids.", "contents": "On the mechanism of 5-oxoproline overproduction in 5-oxoprolinuria. The primary metabolic defect in 5-oxoprolinuria (pyroglutamic aciduria) is the lack of glutathione synthetase. The mechanism of the concomitant overproduction of 5-oxoproline was studied using cell-free extracts of erythrocytes from control individuals and from patients with 5-oxoprolinuria. Such extracts catalyzed the synthesis of 5-oxoproline from L-glutamate. Addition of ATP, Mg ions and alpha-aminobutyrate was needed for optimal activity. The conversion of glutamate to 5-oxoproline occurred in two steps, catalyzed by gamma-glutamyl-cysteine synthetase and gamma-glutamyl cyclotransferase, respectively. Extracts of erythrocytes from control subjects and patients with 5-oxoprolinuria had identical capacity to synthesize 5-oxoproline. The conversion of glutamate to 5-oxoproline was markedly inhibited by reduced glutathione, which exerted its effect on the gamma-glutamyl-cysteine synthetase step. The following mechanism is postulated for the overproduction of 5-oxoproline in 5-oxoprolinuria: the deficiency of glutathione synthetase causes a lack of glutathione which is an essential feed-back inhibitor in the initial step of its biosynthesis. Therefore gamma-glutamyl-cysteine is produced in excessive amounts and it is subsequently converted to 5-oxoproline (and cysteine) by gamma-glutamyl cyclotransferase. This overproduction of 5-oxoproline exceeds the capacity of the 5-oxoprolinase and 5-oxoproline accumulates in body fluids."} {"id": "PMID:1261043", "title": "Enzyme-linked immunoassay of thyrotropin.", "content": "A method was developed for immunoassay of thyrotropin after its conjugation with alkaline phosphatase using the double antibody technique. The dilution of serum resulted in curves parallel to those obtained for standard thyrotropin. The mean recovery of thyrotropin (TSH) added to serum was 97%, and values for serum TSH determined by this method correlated well with those determined by radioimmunoassay. The coefficients of variation were 2 to 7% (within assay) and 10 to 15% (between assay). The method requires minimal equipment, and is less expensive than radioimmunoassay, so it should be useful as a screening test for primary hypothyroidism in cases with above the maximum normal serum TSH level (10 muH/ml).", "contents": "Enzyme-linked immunoassay of thyrotropin. A method was developed for immunoassay of thyrotropin after its conjugation with alkaline phosphatase using the double antibody technique. The dilution of serum resulted in curves parallel to those obtained for standard thyrotropin. The mean recovery of thyrotropin (TSH) added to serum was 97%, and values for serum TSH determined by this method correlated well with those determined by radioimmunoassay. The coefficients of variation were 2 to 7% (within assay) and 10 to 15% (between assay). The method requires minimal equipment, and is less expensive than radioimmunoassay, so it should be useful as a screening test for primary hypothyroidism in cases with above the maximum normal serum TSH level (10 muH/ml)."} {"id": "PMID:1261044", "title": "A method for the estimation of total calcium in serum or heparinized plasma.", "content": "A simple titrimetric method for the determination of total calcium in serum or heparinized plasma is described. After removing interfering substances with an ion-exchange resin, calcium is reacted with glyoxalbis (2-hydroxyanil), GBA, and the resulting red colour titrated with ethylenediaminetetra-acetic acid in the presence of a methanol/glycerol mixture. No special equipment is used, deproteinization is not necessary and only 0.2 ml of sample is required.", "contents": "A method for the estimation of total calcium in serum or heparinized plasma. A simple titrimetric method for the determination of total calcium in serum or heparinized plasma is described. After removing interfering substances with an ion-exchange resin, calcium is reacted with glyoxalbis (2-hydroxyanil), GBA, and the resulting red colour titrated with ethylenediaminetetra-acetic acid in the presence of a methanol/glycerol mixture. No special equipment is used, deproteinization is not necessary and only 0.2 ml of sample is required."} {"id": "PMID:1261045", "title": "Congenital adrenal hyperplasia caused by defect in steroid 21-hydroxylase. Establishment of definitive urinary steroid excretion pattern during first weeks of life.", "content": "The steroid excretion of two female infants with congenital adrenal hyperplasia due to 21-hydroxylase deficiency has been studied during the first weeks of life. The techniques used were gas chromatography on an open-tubular column and combined gas chromatography-mass spectrometry using selected ion recording. During the first days of life 3beta-hydroxy-5-ene steroids predominate and the levels found were considerably greater than those found in normal infants. Selected ion recording mass spectrometry permitted detection of pregnanetriol and 11-oxo-pregnanetriol several days before these steroids could be determined with accuracy by conventional gas chromatography. Pregnanetriol and 11-oxo-pregnanetriol were first detected on the third day of life. The results of this investigation demonstrate that 21-hydroxylase deficiency may be indicated during the first week of life by an increased 3beta-hydroxy-5-ene steroid excretion, but the definitive excretion pattern required for firm diagnosis may not develop for several days. The amounts of the definitive steroids excreted may not be sufficient to be detected by the more usual methods for several weeks.", "contents": "Congenital adrenal hyperplasia caused by defect in steroid 21-hydroxylase. Establishment of definitive urinary steroid excretion pattern during first weeks of life. The steroid excretion of two female infants with congenital adrenal hyperplasia due to 21-hydroxylase deficiency has been studied during the first weeks of life. The techniques used were gas chromatography on an open-tubular column and combined gas chromatography-mass spectrometry using selected ion recording. During the first days of life 3beta-hydroxy-5-ene steroids predominate and the levels found were considerably greater than those found in normal infants. Selected ion recording mass spectrometry permitted detection of pregnanetriol and 11-oxo-pregnanetriol several days before these steroids could be determined with accuracy by conventional gas chromatography. Pregnanetriol and 11-oxo-pregnanetriol were first detected on the third day of life. The results of this investigation demonstrate that 21-hydroxylase deficiency may be indicated during the first week of life by an increased 3beta-hydroxy-5-ene steroid excretion, but the definitive excretion pattern required for firm diagnosis may not develop for several days. The amounts of the definitive steroids excreted may not be sufficient to be detected by the more usual methods for several weeks."} {"id": "PMID:1261046", "title": "Measurement of angiotensin II in human plasma: technical modifications and practical experience.", "content": "This paper presents our experience in measurement of plasma angiotensin II concentration according to the method described by D\u00fcsterdieck, G. and McElwee, G. (1971) Eur. J. Clin. Invest. 2, 32-38. Certain technical modifications of the procedure have been worked out. For each individual plasma sample, the recovery across extraction and elution steps is determined by addition of radio-iodinated angiotensin II. A time-saving recycling elution procedure is described. Evidence for the clinical applicability of the modified method is presented.", "contents": "Measurement of angiotensin II in human plasma: technical modifications and practical experience. This paper presents our experience in measurement of plasma angiotensin II concentration according to the method described by D\u00fcsterdieck, G. and McElwee, G. (1971) Eur. J. Clin. Invest. 2, 32-38. Certain technical modifications of the procedure have been worked out. For each individual plasma sample, the recovery across extraction and elution steps is determined by addition of radio-iodinated angiotensin II. A time-saving recycling elution procedure is described. Evidence for the clinical applicability of the modified method is presented."} {"id": "PMID:1261048", "title": "Conversion of sorbitol to mannitol when used parenterally.", "content": "Conversion of sorbitol to mannitol was shown by the unexpected discovery of the urinary excretion of mannitol when urinary levels were being measured in connection with the surveillance of patients suffering from malnutrition or head injury and receiving total parenteral nutrition: glucose, sorbitol, amino acids and soya oil. The presence of mannitol in thr urine would appear to result from a secondary catabolism through a physiological pathway for the fructose produced by the metabolism of sorbitol not broken down during glycolysis.", "contents": "Conversion of sorbitol to mannitol when used parenterally. Conversion of sorbitol to mannitol was shown by the unexpected discovery of the urinary excretion of mannitol when urinary levels were being measured in connection with the surveillance of patients suffering from malnutrition or head injury and receiving total parenteral nutrition: glucose, sorbitol, amino acids and soya oil. The presence of mannitol in thr urine would appear to result from a secondary catabolism through a physiological pathway for the fructose produced by the metabolism of sorbitol not broken down during glycolysis."} {"id": "PMID:1261049", "title": "Defective erythrocyte pyruvate kinase.", "content": "A defective pyruvate kinase (EC 2.7.1.40) is described. The abnormal PK is characterized by a shift in the R in equilibrium T equilibrium to the T-state. The Ko.5 for the substrate phosphoenol pyruvate is about 6 times higher than for the normal enzyme, while the KM value for the positive effector Fru-1, 6-P2 is increased. In agreement with a shift to the T-state is the increased affinity of the abnormal enzyme for the negative effectors ATP and alanine. The results are discussed in relation to other abnormal pyruvate kinases.", "contents": "Defective erythrocyte pyruvate kinase. A defective pyruvate kinase (EC 2.7.1.40) is described. The abnormal PK is characterized by a shift in the R in equilibrium T equilibrium to the T-state. The Ko.5 for the substrate phosphoenol pyruvate is about 6 times higher than for the normal enzyme, while the KM value for the positive effector Fru-1, 6-P2 is increased. In agreement with a shift to the T-state is the increased affinity of the abnormal enzyme for the negative effectors ATP and alanine. The results are discussed in relation to other abnormal pyruvate kinases."} {"id": "PMID:1261050", "title": "Effect of cotrimoxazole on the response to phenylalanine loading in man.", "content": "Cotrimoxazole impairs the L-phenylalanine tolerance of control subjects as judged by the time course of the plasma phenylalanine concentration and the plasma ratios [phenylalanine]/[tyrosine] after oral and intravenous loading with phenylalanine. These subjects are presumed not to be heterozygous for any of the abnormal recessive genes which cause hyperphenylalaninaemia when they are present in the homozygous state. Patients with classical phenylketonuria did not show this effect. Cotrimoxazole did not affect the renal clearance of phenylalanine. The effect appears to be virtually entirely due to the trimethoprim component as opposed to the sulphamethoxazole component of cotrimoxazole.", "contents": "Effect of cotrimoxazole on the response to phenylalanine loading in man. Cotrimoxazole impairs the L-phenylalanine tolerance of control subjects as judged by the time course of the plasma phenylalanine concentration and the plasma ratios [phenylalanine]/[tyrosine] after oral and intravenous loading with phenylalanine. These subjects are presumed not to be heterozygous for any of the abnormal recessive genes which cause hyperphenylalaninaemia when they are present in the homozygous state. Patients with classical phenylketonuria did not show this effect. Cotrimoxazole did not affect the renal clearance of phenylalanine. The effect appears to be virtually entirely due to the trimethoprim component as opposed to the sulphamethoxazole component of cotrimoxazole."} {"id": "PMID:1261051", "title": "[A two-step determination of plasma total cholesterol and free cholesterol by gas-liquid chromatography. Suggestion for a reference method (author's transl)].", "content": "A technique for the determination of free and esterified plasma cholesterol by gas-liquid chromatography is proposed as a reference method. After a critical examination of all the stages to prove its validity, the method is compared to the usual techniques. Such a comparison confirms that colorimetric methods are more accurate after a lipidic extraction and with a purification step by liquid-solid chromatography.", "contents": "[A two-step determination of plasma total cholesterol and free cholesterol by gas-liquid chromatography. Suggestion for a reference method (author's transl)]. A technique for the determination of free and esterified plasma cholesterol by gas-liquid chromatography is proposed as a reference method. After a critical examination of all the stages to prove its validity, the method is compared to the usual techniques. Such a comparison confirms that colorimetric methods are more accurate after a lipidic extraction and with a purification step by liquid-solid chromatography."} {"id": "PMID:1261052", "title": "A simple method for the determination of free cortisol in plasma, with normal levels in men and women, including women taking low oestrogen contraceptives.", "content": "A small scale equilibrium dialysis method for the measurement of the non-protein bound cortisol in plasma is described. Dialysis is carried out in PTFE cells against an isosmolar Hepes buffer, equilibration occurring within 18 hours. Inter-assay variation was found to be approximately 6%. Samples taken from normal males and females and from oestrogen-treated females were analysed and the results compared with published levels. A significant difference in both the total and free cortisol levels was found between the normals and oestrogen-treated females.", "contents": "A simple method for the determination of free cortisol in plasma, with normal levels in men and women, including women taking low oestrogen contraceptives. A small scale equilibrium dialysis method for the measurement of the non-protein bound cortisol in plasma is described. Dialysis is carried out in PTFE cells against an isosmolar Hepes buffer, equilibration occurring within 18 hours. Inter-assay variation was found to be approximately 6%. Samples taken from normal males and females and from oestrogen-treated females were analysed and the results compared with published levels. A significant difference in both the total and free cortisol levels was found between the normals and oestrogen-treated females."} {"id": "PMID:1261053", "title": "Comparison of plasma progesterone assay in women by competitive protein binding (CPB) and radioimmunoassay (RIA).", "content": "Plasma progesterone levels during the follicular and luteal phases were compared when measured simultaneously by competitive protein binding (using guinea pig sera as binding agent) and radioimmunoassay (antiserum against progesterone-11-alpha-succinyl bovine serum albumin in rabbits), the values obtained were significantly different within each technique, depending on whether previous thin-layer chromatographic purification of the extracts was employed or not. No significant differences were noticed between CPB and RIA when the chromatographic step was used, but when it was omitted, CPB was greater than RIA at the follicular but not at the luteal phase.", "contents": "Comparison of plasma progesterone assay in women by competitive protein binding (CPB) and radioimmunoassay (RIA). Plasma progesterone levels during the follicular and luteal phases were compared when measured simultaneously by competitive protein binding (using guinea pig sera as binding agent) and radioimmunoassay (antiserum against progesterone-11-alpha-succinyl bovine serum albumin in rabbits), the values obtained were significantly different within each technique, depending on whether previous thin-layer chromatographic purification of the extracts was employed or not. No significant differences were noticed between CPB and RIA when the chromatographic step was used, but when it was omitted, CPB was greater than RIA at the follicular but not at the luteal phase."} {"id": "PMID:1261054", "title": "Increased excretion of N-carbamoyl compounds in patients with urea cycle defects.", "content": "Increased urinary levels of N-carbamoyl-beta-alanine, and also, on occasions, of N-carbamoylaspartate, were observed in patients with ornithine carbamoyl-transferase (EC 2.1.3.3) deficiency, argininosuccinate synthetase (EC 6.3.4.5) deficiency and argininosuccinate lyase (EC 4.3.2.1)deficiency, but not in a patient with carbamoylphosphate synthase deficiency. The relevance of these findings to the diagnosis of urea cycle defects is discussed.", "contents": "Increased excretion of N-carbamoyl compounds in patients with urea cycle defects. Increased urinary levels of N-carbamoyl-beta-alanine, and also, on occasions, of N-carbamoylaspartate, were observed in patients with ornithine carbamoyl-transferase (EC 2.1.3.3) deficiency, argininosuccinate synthetase (EC 6.3.4.5) deficiency and argininosuccinate lyase (EC 4.3.2.1)deficiency, but not in a patient with carbamoylphosphate synthase deficiency. The relevance of these findings to the diagnosis of urea cycle defects is discussed."} {"id": "PMID:1261055", "title": "A new reference method for the determination of the oxygen content of blood.", "content": "To be able to determine the slight differences between the theoretical and the actual O2-binding capacity of human haemoglobin, a highly accurate method has been developed for measuring the O2 content of blood samples. It is an adaptation of an established O2 determination in organic microanalysis. The bound O2 of the blood is set free by conversion of HbO2 to Hi, and the O2 stripped from the blood is converted to CO by contact with granular carbon at 1120 degrees C. The CO is then converted to CO2 using CuO at 300 degrees C and the CO2 titrated in a solution of BaCl2, using NaOH of known strength. The measuring system was checked by analysis of 36 samples of air, yielding an O2 content of 20.93 +/- 0.06%. The coefficient of variation calculated from 62 duplicate determinations of samples of human blood was 0.65%.", "contents": "A new reference method for the determination of the oxygen content of blood. To be able to determine the slight differences between the theoretical and the actual O2-binding capacity of human haemoglobin, a highly accurate method has been developed for measuring the O2 content of blood samples. It is an adaptation of an established O2 determination in organic microanalysis. The bound O2 of the blood is set free by conversion of HbO2 to Hi, and the O2 stripped from the blood is converted to CO by contact with granular carbon at 1120 degrees C. The CO is then converted to CO2 using CuO at 300 degrees C and the CO2 titrated in a solution of BaCl2, using NaOH of known strength. The measuring system was checked by analysis of 36 samples of air, yielding an O2 content of 20.93 +/- 0.06%. The coefficient of variation calculated from 62 duplicate determinations of samples of human blood was 0.65%."} {"id": "PMID:1261056", "title": "Photodynamic effects of protoporphyrin on cholesterol and unsaturated fatty acids in erythrocyte membranes in protoporphyria and in normal red blood cells.", "content": "The protoporphyrin-induced photodynamic damage of erythrocytes is caused by photooxidation of a cellular target, localized in the red cell membrane. In model experiments it appeared that some amino acid residues of membrane proteins, unsaturated fatty acid side chains of phospholipids and cholesterol are sensitive to photooxidation, induced by protoporphyrin. In previous studies it has been shown that the membrane damage cannot be attributed to photooxidation of unsaturated fatty acid side chains. Photosensitized peroxidation of cholesterol was studied in model systems, in red cell ghosts and in intact cells. Although cholesterol appeared to be sensitive to protoporphyrin-induced photooxidation in model systems and in red cell ghosts, it could be shown that photohemolysis of red blood cells of patients with erythropoietic protoporphyria cannot be rationalized on the basis of a cholesterol peroxidation.", "contents": "Photodynamic effects of protoporphyrin on cholesterol and unsaturated fatty acids in erythrocyte membranes in protoporphyria and in normal red blood cells. The protoporphyrin-induced photodynamic damage of erythrocytes is caused by photooxidation of a cellular target, localized in the red cell membrane. In model experiments it appeared that some amino acid residues of membrane proteins, unsaturated fatty acid side chains of phospholipids and cholesterol are sensitive to photooxidation, induced by protoporphyrin. In previous studies it has been shown that the membrane damage cannot be attributed to photooxidation of unsaturated fatty acid side chains. Photosensitized peroxidation of cholesterol was studied in model systems, in red cell ghosts and in intact cells. Although cholesterol appeared to be sensitive to protoporphyrin-induced photooxidation in model systems and in red cell ghosts, it could be shown that photohemolysis of red blood cells of patients with erythropoietic protoporphyria cannot be rationalized on the basis of a cholesterol peroxidation."} {"id": "PMID:1261057", "title": "The chemistry of human neonatal femoral epiphyseal cartilage.", "content": "The estimation of cartilage constituents such as hydroxyproline and hexosamine may be used to detect gross changes in the total amount of collagen and matrix. This simple approach, which can only be regarded as a \"screening\" procedure prior to more exhaustive analysis, has been applied to samples of neonatal human cartilage. It is suggested that this method would be useful in analysis cartilage biopsies, especially from patients with bone dysplasias.", "contents": "The chemistry of human neonatal femoral epiphyseal cartilage. The estimation of cartilage constituents such as hydroxyproline and hexosamine may be used to detect gross changes in the total amount of collagen and matrix. This simple approach, which can only be regarded as a \"screening\" procedure prior to more exhaustive analysis, has been applied to samples of neonatal human cartilage. It is suggested that this method would be useful in analysis cartilage biopsies, especially from patients with bone dysplasias."} {"id": "PMID:1261058", "title": "Microdetermination of methylmalonic acid and other short chain dicarboxylic acids by gas chromatography: use in prenatal diagnosis of methylmalonic acidemia and in studies of isovaleric acidemia.", "content": "We have developed a sensitive gas-chromatographic method for the determination of methylmalonic acid and other short chain dircarboxylic acids in biological samples. The method is based on the isolation of the short chain dicarboxylic acid fraction by Dowex 3 X 4 column chromatography followed by gas-chromatography analysis of these acids as methyl esters. 2-n-Pentyl-malonic acid is used as an internal standard. With this method, methylmalonic, succinic and methylsuccinic acids were consistently detected and accurately measured in urine and serum from normal subjects; the identity of these acids being verified by mass spectroscopy. The method's sensitivity permitted its used in the prenatal diagnosis of methylmalonic acidemia by measuring methylmalonic acid in urine and amniotic fluid from three pregnant heterozygous women at risk. One affected (vitamin B-12 responsive type) and two unaffected fetuses were correctly diagnosed prenatally as judged by postnatal investigations. The amount of methylmalonic acid in urine and amniotic fluid was distinctly increased (2 to 14 times normal) in the former and consistently normal in the latter two cases during the third trimester of pregnancy. Effect of prenatal therapy with large doses of vitamin B-12 was closely followed in the first case using analyses of multiple maternal urine specimens. Urinary methylsuccinic acid excretion was studied in two cases with isovaleric acidemia. It was normal in a sample from a patient in remission but was increased seven fold over control during an episode of ketoacidosis.", "contents": "Microdetermination of methylmalonic acid and other short chain dicarboxylic acids by gas chromatography: use in prenatal diagnosis of methylmalonic acidemia and in studies of isovaleric acidemia. We have developed a sensitive gas-chromatographic method for the determination of methylmalonic acid and other short chain dircarboxylic acids in biological samples. The method is based on the isolation of the short chain dicarboxylic acid fraction by Dowex 3 X 4 column chromatography followed by gas-chromatography analysis of these acids as methyl esters. 2-n-Pentyl-malonic acid is used as an internal standard. With this method, methylmalonic, succinic and methylsuccinic acids were consistently detected and accurately measured in urine and serum from normal subjects; the identity of these acids being verified by mass spectroscopy. The method's sensitivity permitted its used in the prenatal diagnosis of methylmalonic acidemia by measuring methylmalonic acid in urine and amniotic fluid from three pregnant heterozygous women at risk. One affected (vitamin B-12 responsive type) and two unaffected fetuses were correctly diagnosed prenatally as judged by postnatal investigations. The amount of methylmalonic acid in urine and amniotic fluid was distinctly increased (2 to 14 times normal) in the former and consistently normal in the latter two cases during the third trimester of pregnancy. Effect of prenatal therapy with large doses of vitamin B-12 was closely followed in the first case using analyses of multiple maternal urine specimens. Urinary methylsuccinic acid excretion was studied in two cases with isovaleric acidemia. It was normal in a sample from a patient in remission but was increased seven fold over control during an episode of ketoacidosis."} {"id": "PMID:1261059", "title": "Toxicology of methyl methacrylate: the rate of disappearance of methyl methacrylate in human blood in vitro.", "content": "1. The rate of disappearance of methyl methacrylate in blood has been determined using an isotope dilution technique. 2. At a concentration of 10(-4) mol dm(-3), methyl methacrylate disappears with pseudo first order kinetics. 3. The half-life of methyl methacrylate in blood at 37 degrees C lies in the range 20--40 min. 4. The half-life showed no dependence on the age or sex of the blood donor. 5. A major, possibly the only, pathway of metabolism is by hydrolysis to methacrylic acid.", "contents": "Toxicology of methyl methacrylate: the rate of disappearance of methyl methacrylate in human blood in vitro. 1. The rate of disappearance of methyl methacrylate in blood has been determined using an isotope dilution technique. 2. At a concentration of 10(-4) mol dm(-3), methyl methacrylate disappears with pseudo first order kinetics. 3. The half-life of methyl methacrylate in blood at 37 degrees C lies in the range 20--40 min. 4. The half-life showed no dependence on the age or sex of the blood donor. 5. A major, possibly the only, pathway of metabolism is by hydrolysis to methacrylic acid."} {"id": "PMID:1261060", "title": "Contributions of other sterols to the estimation of cholesterol.", "content": "The responses of 5alpha-cholestan-3beta-ol, 5alpha-cholest-7-ene-3beta-ol and cholesta-5,7-dien-3beta-ol, normally found in human serum, were examined by: (1) the Liebermann-Burchard reaction, (2) the Zak (ferric chloride) reaction, (3) an enzymatic cholesterol method monitored by estimating the amount of hydrogen peroxide produced, (4) an enzymatic cholesterol method monitored by observing the change in absorbance at 240 nm, and (5) gas chromatography. The results show that none of these methods is specific for cholesterol; contributions from the sterols examined range from zero to more than 150% relative to cholesterol. For the first four methods contributions depend on the conditions under which each test is performed.", "contents": "Contributions of other sterols to the estimation of cholesterol. The responses of 5alpha-cholestan-3beta-ol, 5alpha-cholest-7-ene-3beta-ol and cholesta-5,7-dien-3beta-ol, normally found in human serum, were examined by: (1) the Liebermann-Burchard reaction, (2) the Zak (ferric chloride) reaction, (3) an enzymatic cholesterol method monitored by estimating the amount of hydrogen peroxide produced, (4) an enzymatic cholesterol method monitored by observing the change in absorbance at 240 nm, and (5) gas chromatography. The results show that none of these methods is specific for cholesterol; contributions from the sterols examined range from zero to more than 150% relative to cholesterol. For the first four methods contributions depend on the conditions under which each test is performed."} {"id": "PMID:1261061", "title": "Plasma cholesteryl esters turnover in man: comparison of in vivo and in vitro methods.", "content": "The rate of formation of plasma cholesteryl esters was determined by both in vivo and in vitro methods in 15 subjects. In vivo production of plasma cholesteryl esters was calculated from the specific activity slopes of plasma free and esterified cholesterol after an intravenous injection of [3H] mevalonic acid or [3H] cholesterol incorporated in plasma lipoproteins. In vitro production of cholesteryl esters was estimated by measuring lecithin:cholesterol acyltransferase activity in plasma. Lecithin:cholesterol acyltransferase was estimated by incubating the subjects' own plasma for 1 h at 37 degrees C. The plasma sample used for incubation was collected 2 h after the injection of radioactive precursor (when radioactivity of esterified cholesterol was very low relative to that in free cholesterol and the specific activity of free cholesterol in all of the major plasma lipoprotein classes was identical). The mean value for the production of plasma cholesteryl esters obtained by in vivo method was 126.2 +/- 41.9 mg/h, and it was not significantly different from the mean of 110.5 +/- 25.5 mg/h calculated from the results of in vitro method. The values obtained by the two methods in all 15 subjects had an excellent correlation (r = 0.93). It was found that in normotriglyceridemic subjects the values obtained by the two methods wwere essentially identical, but in hypertriglyceridemic subjects the values obtained by the in vitro method were consistently somewhat lower than the obtained by the in vivo method.", "contents": "Plasma cholesteryl esters turnover in man: comparison of in vivo and in vitro methods. The rate of formation of plasma cholesteryl esters was determined by both in vivo and in vitro methods in 15 subjects. In vivo production of plasma cholesteryl esters was calculated from the specific activity slopes of plasma free and esterified cholesterol after an intravenous injection of [3H] mevalonic acid or [3H] cholesterol incorporated in plasma lipoproteins. In vitro production of cholesteryl esters was estimated by measuring lecithin:cholesterol acyltransferase activity in plasma. Lecithin:cholesterol acyltransferase was estimated by incubating the subjects' own plasma for 1 h at 37 degrees C. The plasma sample used for incubation was collected 2 h after the injection of radioactive precursor (when radioactivity of esterified cholesterol was very low relative to that in free cholesterol and the specific activity of free cholesterol in all of the major plasma lipoprotein classes was identical). The mean value for the production of plasma cholesteryl esters obtained by in vivo method was 126.2 +/- 41.9 mg/h, and it was not significantly different from the mean of 110.5 +/- 25.5 mg/h calculated from the results of in vitro method. The values obtained by the two methods in all 15 subjects had an excellent correlation (r = 0.93). It was found that in normotriglyceridemic subjects the values obtained by the two methods wwere essentially identical, but in hypertriglyceridemic subjects the values obtained by the in vitro method were consistently somewhat lower than the obtained by the in vivo method."} {"id": "PMID:1261063", "title": "Isoelectric focussing of normal human erythrocyte pyruvate kinase (PK) and PK variants with abnormal electrophoretic patterns.", "content": "Isoelectric points of normal human erythrocyte pyruvate kinase (PK) and PK variants with abnormal electrophoretic patterns, were obtained by means of isoelectric focussing. The obtained isoelectric points of normal, PK Nagasaki, PK Tokyo II, PK Ube, and case T.S. were 7.36, 7.38, 7.05, 6.90, and 7.04, respectively, at 6 degrees C. All of the PKs collected after isoelectric focussing were shown to be not of the L-type PK but to be the erythrocyte PK (by means of thin-layer-polyacrylamide gel electrophoresis). The PKs with fast migration had isoelectric points that were shifted to the acidic side as compared with those of the normal subjects. The PK with slow migration had an isoelectric point that was shifted to the alkaline side, demonstrating that the isoelectric points obtained by isoelectric focussing were consistent with the electrophoretic patterns of the crude hemolysates. Isoelectric focussing also revealed the existence of PK variants with abnormal electric net charge, just as well as thin-layer-polyacrylamide gel electrophoresis.", "contents": "Isoelectric focussing of normal human erythrocyte pyruvate kinase (PK) and PK variants with abnormal electrophoretic patterns. Isoelectric points of normal human erythrocyte pyruvate kinase (PK) and PK variants with abnormal electrophoretic patterns, were obtained by means of isoelectric focussing. The obtained isoelectric points of normal, PK Nagasaki, PK Tokyo II, PK Ube, and case T.S. were 7.36, 7.38, 7.05, 6.90, and 7.04, respectively, at 6 degrees C. All of the PKs collected after isoelectric focussing were shown to be not of the L-type PK but to be the erythrocyte PK (by means of thin-layer-polyacrylamide gel electrophoresis). The PKs with fast migration had isoelectric points that were shifted to the acidic side as compared with those of the normal subjects. The PK with slow migration had an isoelectric point that was shifted to the alkaline side, demonstrating that the isoelectric points obtained by isoelectric focussing were consistent with the electrophoretic patterns of the crude hemolysates. Isoelectric focussing also revealed the existence of PK variants with abnormal electric net charge, just as well as thin-layer-polyacrylamide gel electrophoresis."} {"id": "PMID:1261064", "title": "Cardio-cutaneous syndrome (the \"LEOPARD\" syndrome). Review of the literature and a new family.", "content": "Numerous reports of familial cardiac disorders associated with abnormalities of cutaneous pigmentation have appeared in the literature. In some of these there have been other somatic malformations including retardation of growth and anomalous development of the genitalia. In this paper we review the literature and describe another family with multiple lentigines occurring in six members out of eight examined. They were reported to occur in 10 other members not seen by us. The trait showed an autosomal dominant mode of inheritance and appeared to be transmitted by affected fathers. In previous reports transmission has usually been through an affected mother. In five of the six patients examined, only skin abnormalities were detected, but in the propositus the lentigines were associated with retardation of growth, hypertelorism, abnormal genitalia and complete atrioventricular block. The possible explanations for the lack of pleomorphy in other members of the family are discussed.", "contents": "Cardio-cutaneous syndrome (the \"LEOPARD\" syndrome). Review of the literature and a new family. Numerous reports of familial cardiac disorders associated with abnormalities of cutaneous pigmentation have appeared in the literature. In some of these there have been other somatic malformations including retardation of growth and anomalous development of the genitalia. In this paper we review the literature and describe another family with multiple lentigines occurring in six members out of eight examined. They were reported to occur in 10 other members not seen by us. The trait showed an autosomal dominant mode of inheritance and appeared to be transmitted by affected fathers. In previous reports transmission has usually been through an affected mother. In five of the six patients examined, only skin abnormalities were detected, but in the propositus the lentigines were associated with retardation of growth, hypertelorism, abnormal genitalia and complete atrioventricular block. The possible explanations for the lack of pleomorphy in other members of the family are discussed."} {"id": "PMID:1261065", "title": "A genetic study of facial clefting in Northern England.", "content": "A family is reported of 500 facial cleft index cases, attendees for plastic surgery review at hospitals in northern England. Cases displaying malformation syndromes (29 cases, 5.8% of series) were excluded from analysis, after which CL +/- P and CP pedigree data were examined for evidence of polygenic inheritance. The frequencies of affected among parents, aunts and uncles, and first cousins of 324 CL +/- P index cases are respectively 21, 6 and 4 times the population incidence. The sex ratio among index cases increases with severity of defect. Both of these findings are in good agreement with the polygenic mode of inheritance favored for this condition. The frequencies of affected among parents, aunts and uncles, and first cousins of 147 CP index cases are respectively 30, 5, and 9 times the population incidence. Since syndrome-associated clefts have been excluded from analysis, this elevated incidence in first cousins favors the suggestion that multiple genetic forms of CP may exist.", "contents": "A genetic study of facial clefting in Northern England. A family is reported of 500 facial cleft index cases, attendees for plastic surgery review at hospitals in northern England. Cases displaying malformation syndromes (29 cases, 5.8% of series) were excluded from analysis, after which CL +/- P and CP pedigree data were examined for evidence of polygenic inheritance. The frequencies of affected among parents, aunts and uncles, and first cousins of 324 CL +/- P index cases are respectively 21, 6 and 4 times the population incidence. The sex ratio among index cases increases with severity of defect. Both of these findings are in good agreement with the polygenic mode of inheritance favored for this condition. The frequencies of affected among parents, aunts and uncles, and first cousins of 147 CP index cases are respectively 30, 5, and 9 times the population incidence. Since syndrome-associated clefts have been excluded from analysis, this elevated incidence in first cousins favors the suggestion that multiple genetic forms of CP may exist."} {"id": "PMID:1261066", "title": "Hypospadias in successive generations - possible dominant gene inheritance.", "content": "Two families were ascertained with multiple cases of hypospadias. In one family, four generations were reported to be affected and this was proven in three generations. In the second family, a father and two sons were affected. We suggest that dominant gene inheritance may be responsible for a small number of hypospadias cases. The incidence of hypospadias in British Columbia is 1 per 250 live male births and, using Edwards' formula, this gives a theoretical empiric recurrence risk of about 6%.", "contents": "Hypospadias in successive generations - possible dominant gene inheritance. Two families were ascertained with multiple cases of hypospadias. In one family, four generations were reported to be affected and this was proven in three generations. In the second family, a father and two sons were affected. We suggest that dominant gene inheritance may be responsible for a small number of hypospadias cases. The incidence of hypospadias in British Columbia is 1 per 250 live male births and, using Edwards' formula, this gives a theoretical empiric recurrence risk of about 6%."} {"id": "PMID:1261067", "title": "A new chromosome deletion syndrome. Report of a patient with a 46,XY,8p- chromosome constitution.", "content": "A mentally retarded boy with narrow cranium, high forehead, epicanthic folds, flat nasal bridge, low-set but normal ears, retrognathy, short neck and broad chest with wide-set nipples is described. The routine chromosome and banding analyses revealed a 46,XY,8p- chromosome constitution. The parents had normal chromosomes. On the basis of measurements on reflectodensitometer tracings and of measurements of the individual G-bands directly on photographic prints of the normal and abnormal chromosome 8, an intercalary deletion of band p22 seemed most probable. The clinical features of the patient are compared with the 8p- case of Lubs & Lubs (1973) as well as with four other cases of short arm deletion of an unidentified C-autosome. The clinical features of one of these cases were very similar to those of the boy described. An attempt was made to delineate the clinical characteristics of this new chromosomal deletion syndrome.", "contents": "A new chromosome deletion syndrome. Report of a patient with a 46,XY,8p- chromosome constitution. A mentally retarded boy with narrow cranium, high forehead, epicanthic folds, flat nasal bridge, low-set but normal ears, retrognathy, short neck and broad chest with wide-set nipples is described. The routine chromosome and banding analyses revealed a 46,XY,8p- chromosome constitution. The parents had normal chromosomes. On the basis of measurements on reflectodensitometer tracings and of measurements of the individual G-bands directly on photographic prints of the normal and abnormal chromosome 8, an intercalary deletion of band p22 seemed most probable. The clinical features of the patient are compared with the 8p- case of Lubs & Lubs (1973) as well as with four other cases of short arm deletion of an unidentified C-autosome. The clinical features of one of these cases were very similar to those of the boy described. An attempt was made to delineate the clinical characteristics of this new chromosomal deletion syndrome."} {"id": "PMID:1261068", "title": "Re-evaluation of the effect of spray adhesives on human chromosomes.", "content": "The possible effects of spray adhesives on human chromosomes were re-examined in several ways by three different laboratories. A total of 3,382 metaphases were analyzed in a blind-coded fashion. The proportion of abnormal cells, including gaps, was similar in both the control (8.2%) and exposed (8.3%) samples. Our findings do not confirm the original investigation in which the proportion of abnormal cells was found to be significantly higher in the exposed group (8.99%) than in the control group (1.65%). In the earlier study, however, blind-coded slides were not employed. These and other studies show no positive evidence of an effect of spray adhesives on human chromosomes.", "contents": "Re-evaluation of the effect of spray adhesives on human chromosomes. The possible effects of spray adhesives on human chromosomes were re-examined in several ways by three different laboratories. A total of 3,382 metaphases were analyzed in a blind-coded fashion. The proportion of abnormal cells, including gaps, was similar in both the control (8.2%) and exposed (8.3%) samples. Our findings do not confirm the original investigation in which the proportion of abnormal cells was found to be significantly higher in the exposed group (8.99%) than in the control group (1.65%). In the earlier study, however, blind-coded slides were not employed. These and other studies show no positive evidence of an effect of spray adhesives on human chromosomes."} {"id": "PMID:1261069", "title": "Recurrence risks in a consecutive series of congenitally malformed children dying in the perinatal period.", "content": "During a 4 1/2-year period a special study of 207 consecutive perinatal deaths, including clinical, genetical, roentgenological and autopsy investigations, was undertaken with the aim of identifying inherited malformations with a high risk of recurrence to subsequent sibs. Fifty-three of the children dying perinatally were malformed. In 13 cases the cause of the malformation was purely genetic; 11 were caused by mutant genes of large effect, and two by chromosomal aberrations. Information from such a study provides a good basis for genetic counselling of the family.", "contents": "Recurrence risks in a consecutive series of congenitally malformed children dying in the perinatal period. During a 4 1/2-year period a special study of 207 consecutive perinatal deaths, including clinical, genetical, roentgenological and autopsy investigations, was undertaken with the aim of identifying inherited malformations with a high risk of recurrence to subsequent sibs. Fifty-three of the children dying perinatally were malformed. In 13 cases the cause of the malformation was purely genetic; 11 were caused by mutant genes of large effect, and two by chromosomal aberrations. Information from such a study provides a good basis for genetic counselling of the family."} {"id": "PMID:1261070", "title": "Familial spastic paraplegia with distal muscle wasting in the Old Order Amish; atypical Troyer syndrome or \"new\" syndrome.", "content": "The Troyer syndrome was found by Cross & McKusick (1967) in 20 members of 12 Old Order Amish families in Holmes County, Ohio; it is a form of hereditary spastic paraplegia combined with distal muscle wasting, i.e. signs of involvement of lower motor neurons. The condition usually begins at 1 to 2 years and progresses at variable rates. Further manifestations include growth retardation, delayed speech development with dysarthria and drooling, and cerebellar signs; mental functions are usually not affected but severe emotional lability is a common finding. Brothers in a Wisconsin Old Order Amish family are reported with spastic diplegia, mental retardation, behavioral disorder and shortness of stature; the condition apparently is not progressive, and may be a \"new\" syndrome but could also represent a variant of the Troyer syndrome. Autosomal recessive inheritance is most likely, although consanguinity of the parents could not be proven. Another child in this family suffers from focal scleroderma (morphea) which is not related to the neurological syndrome.", "contents": "Familial spastic paraplegia with distal muscle wasting in the Old Order Amish; atypical Troyer syndrome or \"new\" syndrome. The Troyer syndrome was found by Cross & McKusick (1967) in 20 members of 12 Old Order Amish families in Holmes County, Ohio; it is a form of hereditary spastic paraplegia combined with distal muscle wasting, i.e. signs of involvement of lower motor neurons. The condition usually begins at 1 to 2 years and progresses at variable rates. Further manifestations include growth retardation, delayed speech development with dysarthria and drooling, and cerebellar signs; mental functions are usually not affected but severe emotional lability is a common finding. Brothers in a Wisconsin Old Order Amish family are reported with spastic diplegia, mental retardation, behavioral disorder and shortness of stature; the condition apparently is not progressive, and may be a \"new\" syndrome but could also represent a variant of the Troyer syndrome. Autosomal recessive inheritance is most likely, although consanguinity of the parents could not be proven. Another child in this family suffers from focal scleroderma (morphea) which is not related to the neurological syndrome."} {"id": "PMID:1261071", "title": "Autosomal recessive syndrome of pseudogliomantous blindness, osteoporosis and mild mental retardation.", "content": "We report a sibship of three sisters and two brothers who showed osteoporosis of variable severity; the propositus has incapacitating deformities following numerous fractures. Four of the sibs, including three with frequent fractures, were blind from infancy (\"pseudogliomatous blindness\"). In addition, two were mentally retarded. The osteoporosis-pseudoglioma syndrome is inherited as an autosomal recessive trait; similar reports from the literature support this assumption.", "contents": "Autosomal recessive syndrome of pseudogliomantous blindness, osteoporosis and mild mental retardation. We report a sibship of three sisters and two brothers who showed osteoporosis of variable severity; the propositus has incapacitating deformities following numerous fractures. Four of the sibs, including three with frequent fractures, were blind from infancy (\"pseudogliomatous blindness\"). In addition, two were mentally retarded. The osteoporosis-pseudoglioma syndrome is inherited as an autosomal recessive trait; similar reports from the literature support this assumption."} {"id": "PMID:1261072", "title": "The position of the external ear in Turner's syndrome.", "content": "The cephalometric roentgenograms of persons with the syndrome of XO gonadal dysgenesis and its variants, and of those with Noonan's syndrome, were compared with a control sample of unaffected females matched for age. Posterior craniofacial relationships differ between XO and normal individuals, particularly in the region of the external auditory meatus, which is located relatively more inferiorly and anteriorly in XO gonadal dysgenesis subjects than in chromosomally normal persons. Individuals who are mosaics, and those with Noonan's syndrome, do not differ from the unaffected population to the same extent. Although the position of the auricle often changes appreciably with growth when judged by clinical criteria alone, cephalometric analysis of relative ear position may still support the diagnosis of \"low-set\" ears.", "contents": "The position of the external ear in Turner's syndrome. The cephalometric roentgenograms of persons with the syndrome of XO gonadal dysgenesis and its variants, and of those with Noonan's syndrome, were compared with a control sample of unaffected females matched for age. Posterior craniofacial relationships differ between XO and normal individuals, particularly in the region of the external auditory meatus, which is located relatively more inferiorly and anteriorly in XO gonadal dysgenesis subjects than in chromosomally normal persons. Individuals who are mosaics, and those with Noonan's syndrome, do not differ from the unaffected population to the same extent. Although the position of the auricle often changes appreciably with growth when judged by clinical criteria alone, cephalometric analysis of relative ear position may still support the diagnosis of \"low-set\" ears."} {"id": "PMID:1261073", "title": "Ectrodactyly, ectodermal dysplasia and cleft palate (EEC syndrome). Report of a family and review of the literature.", "content": "A family is described in which a father and son are affected with ectrodactyly, ectodermal dysplasia and cleft palate. This particular constellation of major malformations may constitute a variant form of the EEC syndrome which characteristically includes cleft lip with or without cleft palate. From a review of the cases previously reported in the literature, autosomal dominant inheritance is the most likely mode of transmission of these conditions.", "contents": "Ectrodactyly, ectodermal dysplasia and cleft palate (EEC syndrome). Report of a family and review of the literature. A family is described in which a father and son are affected with ectrodactyly, ectodermal dysplasia and cleft palate. This particular constellation of major malformations may constitute a variant form of the EEC syndrome which characteristically includes cleft lip with or without cleft palate. From a review of the cases previously reported in the literature, autosomal dominant inheritance is the most likely mode of transmission of these conditions."} {"id": "PMID:1261074", "title": "Further evidence for the existence of genetically determined metabolic differences between Lp(a+) and Lp(a-) individuals.", "content": "Thirty, presumably healthy, middle-aged males from Northern Sweden were studied in September 1973 and again in February 1975. Mean fasting cholesterol and triglyceride concentrations were significantly higher at the latter investigation than they were at the former in the total group and in the Lp(a+) group, but not among those who were Lp(a-). Furthermore, estimation of free thyroxine factor yielded significantly higher results in the Lp(a-) than in the Lp(a+) group. In a previous paper, we reported significant differences between Lp(a+) and Lp(a-) individuals with respect to the relationships between insulin level and blood glucose concentration, and between insulin level and fasting triglyceride concentration. The combined results of the present and previous studies suggest that inherited metabolic differences exist between Lp(a+) and Lp(a-) individuals. In view of the association which has been found between the phenotype Lp(a+) and coronary heart disease it seems plausible that these differences may be of clinical importance.", "contents": "Further evidence for the existence of genetically determined metabolic differences between Lp(a+) and Lp(a-) individuals. Thirty, presumably healthy, middle-aged males from Northern Sweden were studied in September 1973 and again in February 1975. Mean fasting cholesterol and triglyceride concentrations were significantly higher at the latter investigation than they were at the former in the total group and in the Lp(a+) group, but not among those who were Lp(a-). Furthermore, estimation of free thyroxine factor yielded significantly higher results in the Lp(a-) than in the Lp(a+) group. In a previous paper, we reported significant differences between Lp(a+) and Lp(a-) individuals with respect to the relationships between insulin level and blood glucose concentration, and between insulin level and fasting triglyceride concentration. The combined results of the present and previous studies suggest that inherited metabolic differences exist between Lp(a+) and Lp(a-) individuals. In view of the association which has been found between the phenotype Lp(a+) and coronary heart disease it seems plausible that these differences may be of clinical importance."} {"id": "PMID:1261075", "title": "45,XO/46,XYg dic mosaicism in a patient with ambiguous genitalia.", "content": "45,XO/46,XYq dic mosaicism was found in a patient with ambiguous genitalia. The patient had dysgenetic testis and gonadoblastoma. The same mosaicism was found in skin and gonadal tissue cultured fibroblasts. Localization of the genes related to height and male determination is discussed.", "contents": "45,XO/46,XYg dic mosaicism in a patient with ambiguous genitalia. 45,XO/46,XYq dic mosaicism was found in a patient with ambiguous genitalia. The patient had dysgenetic testis and gonadoblastoma. The same mosaicism was found in skin and gonadal tissue cultured fibroblasts. Localization of the genes related to height and male determination is discussed."} {"id": "PMID:1261076", "title": "The X chromosome in Duchenne's muscular dystrophy.", "content": "A search for deficiencies on one X chromosome of four obligatory and four probable heterozygotes for Duchenne's muscular dystrophy was unsuccessful. This probably excludes deficiencies larger than half the width of any band or interband.", "contents": "The X chromosome in Duchenne's muscular dystrophy. A search for deficiencies on one X chromosome of four obligatory and four probable heterozygotes for Duchenne's muscular dystrophy was unsuccessful. This probably excludes deficiencies larger than half the width of any band or interband."} {"id": "PMID:1261079", "title": "Chromosome survey of new patients admitted to the four maximum security hospitals in the United Kingdom.", "content": "In a survey of male patients admitted to the four maximum security hospitals in the United Kingdom during 1972 and 1973, 26 out of 611 (4.26%) karyotyped were found to have chromosome abnormalities. Of these, 13 (2.13%) had a 47,XYY abnormality; 5 (0.8%) were chromatin positive but two of these had cell lines that included an extra Y chromosome, one being a 48XXYY male and the other a mosaic 48,XXYY/XYY. Eight patients with autosomal abnormalities included two with Down's syndrome and a 47,XY,+21 karyotype, two with small supernumerary chromosomes, 47,XY+mar, and two with inherited balanced translocation. As in the prevalence studies of patients in these high secruity hospitals, the significant finding was the very high frequency of males with extra Y chromosomes. In this survey, it was most marked in the younger patients and particularly in those who were aged 20 years or less (approximately 6%). As a group the XYY males were therefore significantly younger than all other male admissions. As in previous surveys thay were also significantly taller and 60% were 185 cm or more in height. There were no other distinguishing physical characteristics associated with the 47,XYY karytype. In all but two patients the behaviour disturbances were attributable to psychopathic disorders and mental subnormality was diagnosed no more frequently than in the total population studied (approximately 50%).", "contents": "Chromosome survey of new patients admitted to the four maximum security hospitals in the United Kingdom. In a survey of male patients admitted to the four maximum security hospitals in the United Kingdom during 1972 and 1973, 26 out of 611 (4.26%) karyotyped were found to have chromosome abnormalities. Of these, 13 (2.13%) had a 47,XYY abnormality; 5 (0.8%) were chromatin positive but two of these had cell lines that included an extra Y chromosome, one being a 48XXYY male and the other a mosaic 48,XXYY/XYY. Eight patients with autosomal abnormalities included two with Down's syndrome and a 47,XY,+21 karyotype, two with small supernumerary chromosomes, 47,XY+mar, and two with inherited balanced translocation. As in the prevalence studies of patients in these high secruity hospitals, the significant finding was the very high frequency of males with extra Y chromosomes. In this survey, it was most marked in the younger patients and particularly in those who were aged 20 years or less (approximately 6%). As a group the XYY males were therefore significantly younger than all other male admissions. As in previous surveys thay were also significantly taller and 60% were 185 cm or more in height. There were no other distinguishing physical characteristics associated with the 47,XYY karytype. In all but two patients the behaviour disturbances were attributable to psychopathic disorders and mental subnormality was diagnosed no more frequently than in the total population studied (approximately 50%)."} {"id": "PMID:1261080", "title": "Three successive prenatal diagnoses of 47,XY,+21.", "content": "Within 3 working days in September, 1974, we made three prenatal diagnoses of 47,XY,+21 from three women of advanced maternal age. Two were 37 and 38 years old, respectively, and nulliparous. One was 42 years old and had four normal children. The possibility of cell contamination arose when the second diagnosis of trisomy 21 and a male fetus was made. This suspicion increased when the third case was found within 3 working days. All three cases were then studied with both Q and G banding for identification of individual chromosome markers. Fortunately, the distinction was clear by Q-banding. Each case showed characteristic Q-banding polymorphisms in No. 3 and No. 21 chromosomes. It was evident that these were three separate cases. Problems relating to diagnosis of two or more successive identical trisomies of the same sex can be resolved by banding techniques. The response each family had to learning the diagnosis is presented and discussed.", "contents": "Three successive prenatal diagnoses of 47,XY,+21. Within 3 working days in September, 1974, we made three prenatal diagnoses of 47,XY,+21 from three women of advanced maternal age. Two were 37 and 38 years old, respectively, and nulliparous. One was 42 years old and had four normal children. The possibility of cell contamination arose when the second diagnosis of trisomy 21 and a male fetus was made. This suspicion increased when the third case was found within 3 working days. All three cases were then studied with both Q and G banding for identification of individual chromosome markers. Fortunately, the distinction was clear by Q-banding. Each case showed characteristic Q-banding polymorphisms in No. 3 and No. 21 chromosomes. It was evident that these were three separate cases. Problems relating to diagnosis of two or more successive identical trisomies of the same sex can be resolved by banding techniques. The response each family had to learning the diagnosis is presented and discussed."} {"id": "PMID:1261081", "title": "Partial trisomy 5 with a carrier parent t(5p-;9p+).", "content": "The significance of partial trisomies of the B group is as yet unknown. An infant with multiple congenital anomalies was found to have a partial trisomy 5p+ syndrome. The father of this patient demonstrated a 5/9 translocation carrier state. A discussion of the relationship of the partial 5p+ syndrome to the Cri du chat syndrome is noted. Partial trisomy 5 would not appear, as yet, to represent a clearly definable syndrome.", "contents": "Partial trisomy 5 with a carrier parent t(5p-;9p+). The significance of partial trisomies of the B group is as yet unknown. An infant with multiple congenital anomalies was found to have a partial trisomy 5p+ syndrome. The father of this patient demonstrated a 5/9 translocation carrier state. A discussion of the relationship of the partial 5p+ syndrome to the Cri du chat syndrome is noted. Partial trisomy 5 would not appear, as yet, to represent a clearly definable syndrome."} {"id": "PMID:1261086", "title": "Experimental cutaneous leishmaniasis. V. Protective immunity in subclinical and self-healing infection in the mouse.", "content": "This study shows how infection of CBA mice with L. tropica can be manipulated so as to mimic the principal features of both subclinical and self-healing cutaneous leishmaniasis in man. CBA mice were infected with graded inocula of L. tropica promastigotes. The pattern of primary infection was found to be dependent on dose of infecting organisms: mice given low dose inocula (10(2), 10(3)) developed subclinical infections; those given high dose inocula (10(4), 10(5), 10(6)) developed overt, clinical lesions. Size and duration of lesions, and antibody production were directly proportional to dose; delayed hypersensitivity responses were inversely proportional to dose. Protective immunity to challenge infection was induced by both subclinical and clinical infection; and was manifest both during and after the healing stages of primary lesions. Protective immunity was also induced by artificial immunization with sonicated promastigotes in adjuvants but was only manifest if the challenge dose was not too large. The course of challenge infections differed depending on the method of immunization, i.e. whether by infection or artificial immunization. Lymphoid cells from immune CBA mice conferred protection on recipient syngeneic CBA mice against challenge infection; serum from immune mice did not, but suspension of immune peritoneal cells in immune serum enhanced their protective capacity. The experimental induction of protective immunity by low-dose infection, without a clinical allergic response at the site of inoculation, is of importance in designing an immunoprophylactic approach to human leishmaniasis.", "contents": "Experimental cutaneous leishmaniasis. V. Protective immunity in subclinical and self-healing infection in the mouse. This study shows how infection of CBA mice with L. tropica can be manipulated so as to mimic the principal features of both subclinical and self-healing cutaneous leishmaniasis in man. CBA mice were infected with graded inocula of L. tropica promastigotes. The pattern of primary infection was found to be dependent on dose of infecting organisms: mice given low dose inocula (10(2), 10(3)) developed subclinical infections; those given high dose inocula (10(4), 10(5), 10(6)) developed overt, clinical lesions. Size and duration of lesions, and antibody production were directly proportional to dose; delayed hypersensitivity responses were inversely proportional to dose. Protective immunity to challenge infection was induced by both subclinical and clinical infection; and was manifest both during and after the healing stages of primary lesions. Protective immunity was also induced by artificial immunization with sonicated promastigotes in adjuvants but was only manifest if the challenge dose was not too large. The course of challenge infections differed depending on the method of immunization, i.e. whether by infection or artificial immunization. Lymphoid cells from immune CBA mice conferred protection on recipient syngeneic CBA mice against challenge infection; serum from immune mice did not, but suspension of immune peritoneal cells in immune serum enhanced their protective capacity. The experimental induction of protective immunity by low-dose infection, without a clinical allergic response at the site of inoculation, is of importance in designing an immunoprophylactic approach to human leishmaniasis."} {"id": "PMID:1261085", "title": "Effects of acetylsalicylic acid on normal human peripheral blood lymphocytes. Inhibition of mitogen- and antigen-stimulated incorporation of tritiated thymidine.", "content": "Since mechanisms for known anti-inflammatory effects of acetylsalicylic acid (ASA) in rheumatic or immunological diseases are poorly understood, we have studied effects of ASA on in vitro responses of human lymphocytes. Viable lymphocytes from normal individuals were cultured sterilely at 10(6) cells/ml in RPMI 1640 supplemented with 20% pooled AB plasma, at 37degreesC, 5% CO2. Replicate cultures were incubated with or without adding ASA and unstimulated or stimulated by PHA, Con-A, PWN, Candida, or SK-SD. Cultures contained greater than 95% mononuclear and greater 80% viable cells before pulsing with [3H]TdR, harvesting, and counting. Results indicated that adding 3-40 mg/100 ml ASA to culture resulted in significant inhibition of mitogen-induced blastogenesis. As little as 5-10 mg/100 ml ASA caused approximately 30% inhibition of [3H]TdR uptake, and virtually complete inhibition occurred with 20 mg/100 ml of ASA. Stimulation of cells from persons who were skin-test positive for Candida and SK-SD by these antigens in vitro was similarly suppressed by ASA. Exposure of cells to ASA before stimulation in medium without ASA still demonstrated time- and concentration-dependent inhibition of blastogenesis. Cells from normal individuals, obtained immediately and several days after orally ingesting therapeutic amounts of ASA (plasma level 23 mg/100 ml), cultured in medium without ASA, stimulated less well to mitogens that did cells obtained from these persons before ASA ingestion. These data show that: (i) therapeutic concentrations of ASA inhibit lymphocyte blastogenesis to both mitogens and antigens; (ii) inhibition was non-cytotoxic and partially reversible; and (iii) cells from normal subjects who had ingested therapeutic amounts of ASA responded less well to mitogens in vitro than before ASA ingestion. These observations are pertinent to clinical investigations of cellular immune response of individuals on drug therapy and to the possible mechanism(s) of anti-inflammatory action of ASA in immunologically mediated diseases.", "contents": "Effects of acetylsalicylic acid on normal human peripheral blood lymphocytes. Inhibition of mitogen- and antigen-stimulated incorporation of tritiated thymidine. Since mechanisms for known anti-inflammatory effects of acetylsalicylic acid (ASA) in rheumatic or immunological diseases are poorly understood, we have studied effects of ASA on in vitro responses of human lymphocytes. Viable lymphocytes from normal individuals were cultured sterilely at 10(6) cells/ml in RPMI 1640 supplemented with 20% pooled AB plasma, at 37degreesC, 5% CO2. Replicate cultures were incubated with or without adding ASA and unstimulated or stimulated by PHA, Con-A, PWN, Candida, or SK-SD. Cultures contained greater than 95% mononuclear and greater 80% viable cells before pulsing with [3H]TdR, harvesting, and counting. Results indicated that adding 3-40 mg/100 ml ASA to culture resulted in significant inhibition of mitogen-induced blastogenesis. As little as 5-10 mg/100 ml ASA caused approximately 30% inhibition of [3H]TdR uptake, and virtually complete inhibition occurred with 20 mg/100 ml of ASA. Stimulation of cells from persons who were skin-test positive for Candida and SK-SD by these antigens in vitro was similarly suppressed by ASA. Exposure of cells to ASA before stimulation in medium without ASA still demonstrated time- and concentration-dependent inhibition of blastogenesis. Cells from normal individuals, obtained immediately and several days after orally ingesting therapeutic amounts of ASA (plasma level 23 mg/100 ml), cultured in medium without ASA, stimulated less well to mitogens that did cells obtained from these persons before ASA ingestion. These data show that: (i) therapeutic concentrations of ASA inhibit lymphocyte blastogenesis to both mitogens and antigens; (ii) inhibition was non-cytotoxic and partially reversible; and (iii) cells from normal subjects who had ingested therapeutic amounts of ASA responded less well to mitogens in vitro than before ASA ingestion. These observations are pertinent to clinical investigations of cellular immune response of individuals on drug therapy and to the possible mechanism(s) of anti-inflammatory action of ASA in immunologically mediated diseases."} {"id": "PMID:1261087", "title": "In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. II. Pathological tissues.", "content": "An in vitro culture technique has been used to study synthesis of proteins by biopsies of human gastrointestinal mucosa which were obtained at endoscopy or surgery from patients with biliary gastritis, atrophic gastritis, peptic ulcer, gastric cancer, coeliac disease, Crohn's disease and ulcerative colitis. As in normal mucosa, immunoglobulin synthesis was found in all sites, but marked increases, especially in IgG, were seen in biliary gastritis and ulcerative colitis. In untreated coeliac disease, synthesis of IgG and IgM was increased. Synthesis of complement components did not differ from that found in normal mucosa. Increased lysozyme synthesis was seen in Crohn's disease. This study shows that useful information may be acquired from short-term culture studies of the small biopsies obtained with fibre optic endoscopes.", "contents": "In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. II. Pathological tissues. An in vitro culture technique has been used to study synthesis of proteins by biopsies of human gastrointestinal mucosa which were obtained at endoscopy or surgery from patients with biliary gastritis, atrophic gastritis, peptic ulcer, gastric cancer, coeliac disease, Crohn's disease and ulcerative colitis. As in normal mucosa, immunoglobulin synthesis was found in all sites, but marked increases, especially in IgG, were seen in biliary gastritis and ulcerative colitis. In untreated coeliac disease, synthesis of IgG and IgM was increased. Synthesis of complement components did not differ from that found in normal mucosa. Increased lysozyme synthesis was seen in Crohn's disease. This study shows that useful information may be acquired from short-term culture studies of the small biopsies obtained with fibre optic endoscopes."} {"id": "PMID:1261088", "title": "Binding of thyroid microsomes by lymphocytes from patients with thyroid disease and normal subjects.", "content": "Lymphocytes that could bind 125I-labelled thyroid microsomal membranes (ABL) were present in the peripheral blood of patients with various types of thyroid disease as well as in normal healthy subjects. In patients with anti-thyroid cytoplasmic antibodies the number of ABL was about three times normal (11-21 +/- 0-60 compared with 3-26 +/- 0-18 per 10(4) lymphocytes). In contrast, in patients with thyroid disease without anti-thyroid cytoplasmic antibodies, the number of antigen-binding lymphocytes was not significantly greater than in the normal controls (3-94 +/- 0.14 per 10(4) lymphocytes). The binding of thyroid microsomes by antigen-binding lymphocytes could be blocked by thyroid microsomes but not by thyroid mitochondrial membranes, thyroglobulin or liver microsomes.", "contents": "Binding of thyroid microsomes by lymphocytes from patients with thyroid disease and normal subjects. Lymphocytes that could bind 125I-labelled thyroid microsomal membranes (ABL) were present in the peripheral blood of patients with various types of thyroid disease as well as in normal healthy subjects. In patients with anti-thyroid cytoplasmic antibodies the number of ABL was about three times normal (11-21 +/- 0-60 compared with 3-26 +/- 0-18 per 10(4) lymphocytes). In contrast, in patients with thyroid disease without anti-thyroid cytoplasmic antibodies, the number of antigen-binding lymphocytes was not significantly greater than in the normal controls (3-94 +/- 0.14 per 10(4) lymphocytes). The binding of thyroid microsomes by antigen-binding lymphocytes could be blocked by thyroid microsomes but not by thyroid mitochondrial membranes, thyroglobulin or liver microsomes."} {"id": "PMID:1261089", "title": "Autoimmunity and viral infection in diabetes mellitus.", "content": "Forty-three newly diagnosed insulin-dependent diabetics and thirty control subjects have been examined for cellular hypersensitivity to different pancreatic preparations, rat liver mitochondria and Coxsackie B4 virus. Evidence for cellular hypersensitivity to the pancreatic preparations was shown in the diabetic group, in whom the hypersensitivity to the pancreatic preparations was found to correlate with hypersensitivity to rat liver mitochondria. Hypersensitivity to Coxsackie B4 virus was not found to differ significantly in the diabetic and control groups. Hypersensitivity to liver mitochondria appeared to decrease over a 1-year period. There was an indication that hypersensitivity to Coxsackie B4 was greatest 3 months after diagnosis.", "contents": "Autoimmunity and viral infection in diabetes mellitus. Forty-three newly diagnosed insulin-dependent diabetics and thirty control subjects have been examined for cellular hypersensitivity to different pancreatic preparations, rat liver mitochondria and Coxsackie B4 virus. Evidence for cellular hypersensitivity to the pancreatic preparations was shown in the diabetic group, in whom the hypersensitivity to the pancreatic preparations was found to correlate with hypersensitivity to rat liver mitochondria. Hypersensitivity to Coxsackie B4 virus was not found to differ significantly in the diabetic and control groups. Hypersensitivity to liver mitochondria appeared to decrease over a 1-year period. There was an indication that hypersensitivity to Coxsackie B4 was greatest 3 months after diagnosis."} {"id": "PMID:1261090", "title": "IgM levels and IgM-mediated immune responses in patients with acute hepatitis A, acute hepatitis B and chronic HB antigenaemia.", "content": "Immunoglobulin M (IgM) levels and their relationship to isohaemagglutinins, febrile agglutinins, sheep cell agglutinins, and rheumatoid factor were measured in patients with acute hepatitis A, acute hepatitis B, chronic hepatitis B antigenaemia, and normal control populations. Significant IgM elevations were observed in both types of acute hepatitis, but not in chronic hepatitis B antigenaemia. There was no correlation of the IgM level with either the prevalence or titre of any IgM-mediated immune response studied. These data suggest that the IgM elevations in both types of hepatitis may reflect virus-specific IgM synthesis.", "contents": "IgM levels and IgM-mediated immune responses in patients with acute hepatitis A, acute hepatitis B and chronic HB antigenaemia. Immunoglobulin M (IgM) levels and their relationship to isohaemagglutinins, febrile agglutinins, sheep cell agglutinins, and rheumatoid factor were measured in patients with acute hepatitis A, acute hepatitis B, chronic hepatitis B antigenaemia, and normal control populations. Significant IgM elevations were observed in both types of acute hepatitis, but not in chronic hepatitis B antigenaemia. There was no correlation of the IgM level with either the prevalence or titre of any IgM-mediated immune response studied. These data suggest that the IgM elevations in both types of hepatitis may reflect virus-specific IgM synthesis."} {"id": "PMID:1261091", "title": "Intracellular immunoglobulin production in vitro by lymphocytes from patients with hypogammaglobulinaemia and their effect on normal lymphocytes.", "content": "The ability of peripheral blood lymphocytes from twenty-two patients with late onset (acquired or common variable) hypogammaglobulinaemia to produce immunoglobulin was assessed by the immunofluorescent detection of intracytoplasmic immunoglobulin (Ic-Ig) in cultures stimulated with pokeweed mitogen (PWM). Intracellular immunoglobulin was found in 4-9-26% of cultured cells from eighteen out of nineteen controls. In contrast nineteen out of twenty-two patients with hypogammaglobulinaemia showed values less than 1% and in ten no Ic-Ig was detected. Two of the remaining three patients showed normal values. Lymphocytes from eleven patients showing less than 1% positive cells were selected for mixture experiments. Lymphocytes from five of the eleven patients strongly depressed immunoglobulin synthesis by normal lymphocytes when mixed together in the presence of PWM. However, lymphocytes from these individual patients did not depress immunoglobulin production in all normal controls.", "contents": "Intracellular immunoglobulin production in vitro by lymphocytes from patients with hypogammaglobulinaemia and their effect on normal lymphocytes. The ability of peripheral blood lymphocytes from twenty-two patients with late onset (acquired or common variable) hypogammaglobulinaemia to produce immunoglobulin was assessed by the immunofluorescent detection of intracytoplasmic immunoglobulin (Ic-Ig) in cultures stimulated with pokeweed mitogen (PWM). Intracellular immunoglobulin was found in 4-9-26% of cultured cells from eighteen out of nineteen controls. In contrast nineteen out of twenty-two patients with hypogammaglobulinaemia showed values less than 1% and in ten no Ic-Ig was detected. Two of the remaining three patients showed normal values. Lymphocytes from eleven patients showing less than 1% positive cells were selected for mixture experiments. Lymphocytes from five of the eleven patients strongly depressed immunoglobulin synthesis by normal lymphocytes when mixed together in the presence of PWM. However, lymphocytes from these individual patients did not depress immunoglobulin production in all normal controls."} {"id": "PMID:1261092", "title": "In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. I. Normal tissues.", "content": "An in vitro culture technique has been used to demonstrate synthesis of proteins by human gastrointestinal tissues cultured in vitro. Histologically normal tissues were obtained endoscopically and surgically. IgA and secretory component (SC) were produced in all sites, but the relative intensity of IgA synthesis and SC synthesis varied. In stomach and small intestine the intensity of IgA synthesis was greater than that of SC, but in large bowel mucosa, there appeared to be an excess of SC synthesis. Synthesis of IgG and IgM was also found in all sites. Complement proteins were produced by some of the intestinal biopsies, and by parotid gland. Lysozyme was synthesized by parotid gland and by gastric mucosa, and to a lesser extent in small intestine, and rarely in large intestine. The results suggest that in addition to the local mucosal IgA system the local production of other immunoglobulins, as well as non-immunoglobulin humoral defence factors, may be important host defences of the normal gastrointestinal tract.", "contents": "In vitro synthesis of immunoglobulins, secretory component, complement and lysozyme by human gastrointestinal tissues. I. Normal tissues. An in vitro culture technique has been used to demonstrate synthesis of proteins by human gastrointestinal tissues cultured in vitro. Histologically normal tissues were obtained endoscopically and surgically. IgA and secretory component (SC) were produced in all sites, but the relative intensity of IgA synthesis and SC synthesis varied. In stomach and small intestine the intensity of IgA synthesis was greater than that of SC, but in large bowel mucosa, there appeared to be an excess of SC synthesis. Synthesis of IgG and IgM was also found in all sites. Complement proteins were produced by some of the intestinal biopsies, and by parotid gland. Lysozyme was synthesized by parotid gland and by gastric mucosa, and to a lesser extent in small intestine, and rarely in large intestine. The results suggest that in addition to the local mucosal IgA system the local production of other immunoglobulins, as well as non-immunoglobulin humoral defence factors, may be important host defences of the normal gastrointestinal tract."} {"id": "PMID:1261093", "title": "Characteristics of the effector cells mediating cytotoxicity against antibody-coated target cells. III. Ultrastructural studies.", "content": "On the basis of electron microscopic observations, four types of cells apparently cytotoxic for antibody-coated chicken erythrocytes were identified in non-immune mouse spleen; monocytes, polymorphonuclear leucocytes, immature granulocytes and a type of lymphoid cell. Both phagocytosis and extracellular lysis of target cells were observed. Monocytes and polymorphonuclears were able to interact with the target cell by both mechanisms while the intermediary granulocytes and lymphoid cells were only capable of extracellular lysis. It is argued that these observations provide a morphological basis for the previous classification of antibody-dependent cytotoxic cells into myeloid and lymphoid cells (Greenberg et al., 1973b, 1975).", "contents": "Characteristics of the effector cells mediating cytotoxicity against antibody-coated target cells. III. Ultrastructural studies. On the basis of electron microscopic observations, four types of cells apparently cytotoxic for antibody-coated chicken erythrocytes were identified in non-immune mouse spleen; monocytes, polymorphonuclear leucocytes, immature granulocytes and a type of lymphoid cell. Both phagocytosis and extracellular lysis of target cells were observed. Monocytes and polymorphonuclears were able to interact with the target cell by both mechanisms while the intermediary granulocytes and lymphoid cells were only capable of extracellular lysis. It is argued that these observations provide a morphological basis for the previous classification of antibody-dependent cytotoxic cells into myeloid and lymphoid cells (Greenberg et al., 1973b, 1975)."} {"id": "PMID:1261094", "title": "Ultrastructural studies of mouse leucocytes showing surface binding of peroxidase-conjugated lectins.", "content": "Examination in the electron microscope of mouse spleen cells treated with conjugates of wheatgerm agglutinin and horseradish peroxidase has shown the surface of myeloid cells to be heavily stained. Resting lymphocytes were unstained but became positive after stimulation by phytohaemagglutinin or concanavalin A, suggesting a relationship between the presence of this surface component and the functional state of the cell and providing a further point of similarity between myeloid and lymphoblastoid cells. The conjugates have also been useful in tracing the fate of surface carbohydrates during phagocytosis.", "contents": "Ultrastructural studies of mouse leucocytes showing surface binding of peroxidase-conjugated lectins. Examination in the electron microscope of mouse spleen cells treated with conjugates of wheatgerm agglutinin and horseradish peroxidase has shown the surface of myeloid cells to be heavily stained. Resting lymphocytes were unstained but became positive after stimulation by phytohaemagglutinin or concanavalin A, suggesting a relationship between the presence of this surface component and the functional state of the cell and providing a further point of similarity between myeloid and lymphoblastoid cells. The conjugates have also been useful in tracing the fate of surface carbohydrates during phagocytosis."} {"id": "PMID:1261101", "title": "Significance of urinary excretion of fibrin degradation products during treatment of glomerulonephritis.", "content": "189 patients with various types of glomerular disease were studied. Creatinine clearance, protein excretion and urinary excretion of fibrin degradation products (FDPs) were measured before and at various intervals (up to 42 months) after starting treatment with indomethacin, alone or in combination with other drugs. The following observations were made: a. Patients with a urinary FDP in excess of 2 mg/24 hours before treatment had a significantly lower creatinine clearance and a significantly higher protein excretion than patients excreting less than 2 mg FDP/24 hours, indicating that FDP excretion reflects the severity of the renal disease. b. During treatment, the incidence of high FDP excretion decreases progressively, but remains high in patients who ultimately develop renal insufficiency. c. There is no correlation between the initial value of FDP excretion and the subsequent changes in creatinine clearance and proteinuria during treatment. This implies either that the initial FDP excretion has no prognostic value or, perhaps more likely, that disease activity is modified by treatment. d. The best correlation between FDP excretion and evolution is found in proliferative glomerulonephritis. There are reason to suppose that, in this group at least, the treatment influenced the evolution of the disease.", "contents": "Significance of urinary excretion of fibrin degradation products during treatment of glomerulonephritis. 189 patients with various types of glomerular disease were studied. Creatinine clearance, protein excretion and urinary excretion of fibrin degradation products (FDPs) were measured before and at various intervals (up to 42 months) after starting treatment with indomethacin, alone or in combination with other drugs. The following observations were made: a. Patients with a urinary FDP in excess of 2 mg/24 hours before treatment had a significantly lower creatinine clearance and a significantly higher protein excretion than patients excreting less than 2 mg FDP/24 hours, indicating that FDP excretion reflects the severity of the renal disease. b. During treatment, the incidence of high FDP excretion decreases progressively, but remains high in patients who ultimately develop renal insufficiency. c. There is no correlation between the initial value of FDP excretion and the subsequent changes in creatinine clearance and proteinuria during treatment. This implies either that the initial FDP excretion has no prognostic value or, perhaps more likely, that disease activity is modified by treatment. d. The best correlation between FDP excretion and evolution is found in proliferative glomerulonephritis. There are reason to suppose that, in this group at least, the treatment influenced the evolution of the disease."} {"id": "PMID:1261102", "title": "The protein binding of diazepam and N-demethyldiazepam in patients with poor renal function.", "content": "The plasma protein binding of diazepam and of its main metabolite, N-demethyldiazepam, was measured in patients with renal disease and in healthy volunteers by ultracentrifugation. The total and non-protein bound concentrations of diazepam and N-demethyldiazepam, and the concentration of unconjugated oxazepam in the plasma were determined by gas chromatography after an oral 10 mg dose of diazepam. In the volunteers 98% of diazepam and N-demethyldiazepam were bound to the plasma proteins. In patients with renal disease the corresponding values were 92% and 95%, respectively. In the patients with renal disease no correlation could be found between the percent protein binding of diazepam or N-demethyldiazepam in the plasma and the serum creatinine concentration. Considerable variations in diazepam concentrations at 1 and 24 hours and in N-demethyldiazepam concentrations at 24 hours were found in the patients with renal disease. In contrast to the volunteers, 5 patients out of 28 with renal disease had measurable amounts of unconjugated oxazepam in the plasma. The deficient ability of the plasma proteins of patients with renal disease to bind diazepam may increase its clinical effect.", "contents": "The protein binding of diazepam and N-demethyldiazepam in patients with poor renal function. The plasma protein binding of diazepam and of its main metabolite, N-demethyldiazepam, was measured in patients with renal disease and in healthy volunteers by ultracentrifugation. The total and non-protein bound concentrations of diazepam and N-demethyldiazepam, and the concentration of unconjugated oxazepam in the plasma were determined by gas chromatography after an oral 10 mg dose of diazepam. In the volunteers 98% of diazepam and N-demethyldiazepam were bound to the plasma proteins. In patients with renal disease the corresponding values were 92% and 95%, respectively. In the patients with renal disease no correlation could be found between the percent protein binding of diazepam or N-demethyldiazepam in the plasma and the serum creatinine concentration. Considerable variations in diazepam concentrations at 1 and 24 hours and in N-demethyldiazepam concentrations at 24 hours were found in the patients with renal disease. In contrast to the volunteers, 5 patients out of 28 with renal disease had measurable amounts of unconjugated oxazepam in the plasma. The deficient ability of the plasma proteins of patients with renal disease to bind diazepam may increase its clinical effect."} {"id": "PMID:1261103", "title": "Hepatorenal syndrome following hemihepatectomy.", "content": "The hepatorenal syndrome following right hemiphepatectomy is reported in a previously healthy patient who sustained a shotgun wound in the abdomen. In spite of the development of severe oliguric renal insufficiency and the administration of massive amounts of volume expanders and furosemide, the urine sodium concentration remained very low, therby excluding the diagnosis of acute tubular necrosis. Although severe hyperbilirubinemia developed, the prothrombin time was only slightly abnormal and the liver doubled in size in the 2 weeks after surgery. The study of functional renal failure in patients with liver disease other than decompensated cirrhosis and with significant preservation of hepatic function may suggest that factors other than a circulating toxin participate in mediating the hepatorenal syndrome.", "contents": "Hepatorenal syndrome following hemihepatectomy. The hepatorenal syndrome following right hemiphepatectomy is reported in a previously healthy patient who sustained a shotgun wound in the abdomen. In spite of the development of severe oliguric renal insufficiency and the administration of massive amounts of volume expanders and furosemide, the urine sodium concentration remained very low, therby excluding the diagnosis of acute tubular necrosis. Although severe hyperbilirubinemia developed, the prothrombin time was only slightly abnormal and the liver doubled in size in the 2 weeks after surgery. The study of functional renal failure in patients with liver disease other than decompensated cirrhosis and with significant preservation of hepatic function may suggest that factors other than a circulating toxin participate in mediating the hepatorenal syndrome."} {"id": "PMID:1261104", "title": "Chemical properties of glomerular basement membrane in congenital nephrotic syndrome.", "content": "Glomerular basement membranes have been isolated from kidneys of three children presenting with a congenital nephrotic syndrome. The histology of renal tissue was characterized by an increase of the mesangial area mainly due to matrix. Immunofluorescent studies showed no positive staining. After isolation, the glomerular basement membranes contained no more cellular contaminants than normal membranes. Isolated abnormal membranes exhibited, as normal preparations, less than 1% DNA, RNA, phospholipids or glycosaminoglycans. Since the protein content of both membrane preparations was comparable, significant contamination by non-proteic material did not seem likely. Although the amino acid and carbohydrate composition of both normal and abnormal membranes was very similar, the folowing statistically significant differences were observed: diseased membranes exhibited an increased number of hydroxylysine, 3- and 4-hydroxyproline residues, and an increased content of glucosyl-galactosyl-hydroxlysine units. The data suggest that, in the congenital nephrotic syndrome, the production of disaccharide-rich glomerular basement membrane subunits is enhanced, which could interfere with the packing of the peptide chains and therefore account for the altered permeability of the membrane observed in this disease.", "contents": "Chemical properties of glomerular basement membrane in congenital nephrotic syndrome. Glomerular basement membranes have been isolated from kidneys of three children presenting with a congenital nephrotic syndrome. The histology of renal tissue was characterized by an increase of the mesangial area mainly due to matrix. Immunofluorescent studies showed no positive staining. After isolation, the glomerular basement membranes contained no more cellular contaminants than normal membranes. Isolated abnormal membranes exhibited, as normal preparations, less than 1% DNA, RNA, phospholipids or glycosaminoglycans. Since the protein content of both membrane preparations was comparable, significant contamination by non-proteic material did not seem likely. Although the amino acid and carbohydrate composition of both normal and abnormal membranes was very similar, the folowing statistically significant differences were observed: diseased membranes exhibited an increased number of hydroxylysine, 3- and 4-hydroxyproline residues, and an increased content of glucosyl-galactosyl-hydroxlysine units. The data suggest that, in the congenital nephrotic syndrome, the production of disaccharide-rich glomerular basement membrane subunits is enhanced, which could interfere with the packing of the peptide chains and therefore account for the altered permeability of the membrane observed in this disease."} {"id": "PMID:1261108", "title": "Classification of the skeletal dysplasias and the radiologic approach to their differentiation.", "content": "This chapter presents a radiological classification of skeletal dysplasias, based upon the approved nomenclature of this group of disorders. This provides a practical approach to the problem of the radiological diagnosis of patients suffering from intrinsic diseases of the skeletal system, and should encourage universal adoption of the Paris Nomenclature of skeletal dysplasias in the future. Unclassifiable disorders eventually may be submitted to another conference of authorities in the field for the purpose of further refinement of the present classification.", "contents": "Classification of the skeletal dysplasias and the radiologic approach to their differentiation. This chapter presents a radiological classification of skeletal dysplasias, based upon the approved nomenclature of this group of disorders. This provides a practical approach to the problem of the radiological diagnosis of patients suffering from intrinsic diseases of the skeletal system, and should encourage universal adoption of the Paris Nomenclature of skeletal dysplasias in the future. Unclassifiable disorders eventually may be submitted to another conference of authorities in the field for the purpose of further refinement of the present classification."} {"id": "PMID:1261107", "title": "Acrodysplasias peripheral dysostosis, acrodysostosis and Thiemann's disease.", "content": "The acrodysplasias (peripheral dysostoses) are a heterogeneous group of disorders which are characterized primarily by shortened hands and feet. These disorders are associated with phalangeal cone shaped epiphyses of the hands. Further classification of these disorders is based on the type and distribution of the cone shaped epiphyses and on a variety of extra-skeletal anomalies. Thiemann's disease, added arbitrarily to this group, is an entirely different, possibly extinct \"necrosis\" of the mesophalangeal epiphysis, observed in males during or after puberty.", "contents": "Acrodysplasias peripheral dysostosis, acrodysostosis and Thiemann's disease. The acrodysplasias (peripheral dysostoses) are a heterogeneous group of disorders which are characterized primarily by shortened hands and feet. These disorders are associated with phalangeal cone shaped epiphyses of the hands. Further classification of these disorders is based on the type and distribution of the cone shaped epiphyses and on a variety of extra-skeletal anomalies. Thiemann's disease, added arbitrarily to this group, is an entirely different, possibly extinct \"necrosis\" of the mesophalangeal epiphysis, observed in males during or after puberty."} {"id": "PMID:1261109", "title": "Achondroplastic and hypochondroplastic dwarfism.", "content": "To ensure proper management, prognosis and genetic counseling among patients with chondrodystrophy a specific diagnosis is critical. Achondroplasia is the most common intrinsic bone dysplasia which results in short-limbed dwarfism. Because of its frequency, it is the most completely documented and understood of these conditions. Emphasis has been given to the various characteristics which allow an exact diagnosis to be made. Hypochondroplasia can be misdiagnosed unless attention is paid to the many differences which distinguish it as a separated disorder. Some ten other conditions must be considered in the differential diagnosis of these conditions.", "contents": "Achondroplastic and hypochondroplastic dwarfism. To ensure proper management, prognosis and genetic counseling among patients with chondrodystrophy a specific diagnosis is critical. Achondroplasia is the most common intrinsic bone dysplasia which results in short-limbed dwarfism. Because of its frequency, it is the most completely documented and understood of these conditions. Emphasis has been given to the various characteristics which allow an exact diagnosis to be made. Hypochondroplasia can be misdiagnosed unless attention is paid to the many differences which distinguish it as a separated disorder. Some ten other conditions must be considered in the differential diagnosis of these conditions."} {"id": "PMID:1261110", "title": "Irvine ankle arthroplasty. Prosthetic design and surgical technique.", "content": "A total ankle arthroplasty (IAA) design is presented for highly selected cases. The design stems from investigations on the anatomical and biomechanical characteristics of the human ankle joint. The prostheses are inserted through an anterior approach. Full weight-bearing is well tolerated within a few days. The immediate results on 20 ankles are most encouraging.", "contents": "Irvine ankle arthroplasty. Prosthetic design and surgical technique. A total ankle arthroplasty (IAA) design is presented for highly selected cases. The design stems from investigations on the anatomical and biomechanical characteristics of the human ankle joint. The prostheses are inserted through an anterior approach. Full weight-bearing is well tolerated within a few days. The immediate results on 20 ankles are most encouraging."} {"id": "PMID:1261112", "title": "Arthrodesis in the presence of infection.", "content": "Eradication of the joint infection with severe joint destruction in the presence of active infection has been accomplished in 8 patients by radical debridement, stable fixation and adequate postoperative drainage of wound. All patients were successfully treated by a one-stage primary arthrodesis and all patients went on to develop a solid fusion.", "contents": "Arthrodesis in the presence of infection. Eradication of the joint infection with severe joint destruction in the presence of active infection has been accomplished in 8 patients by radical debridement, stable fixation and adequate postoperative drainage of wound. All patients were successfully treated by a one-stage primary arthrodesis and all patients went on to develop a solid fusion."} {"id": "PMID:1261113", "title": "Pyarthrosis of the manubriosternal joint.", "content": "This is a case report of primary osteomyelitis of the sternum, the only case of pyarthrosis of the manubriosternal joint the authors are able to find in the American literature. The diagnosis was established by tomogram and open biopsy. The treatment was thorough and specific antibiotic coverage.", "contents": "Pyarthrosis of the manubriosternal joint. This is a case report of primary osteomyelitis of the sternum, the only case of pyarthrosis of the manubriosternal joint the authors are able to find in the American literature. The diagnosis was established by tomogram and open biopsy. The treatment was thorough and specific antibiotic coverage."} {"id": "PMID:1261114", "title": "Neurilemmomas of the forearm and hand.", "content": "Neurilemmoma is the most common tumor arising from peripheral nerves. Although infrequently encountered, it must be included in the differential diagnosis of soft tissue tumors. Because of its cystic consistency, a neurilemmoma in the hand or wrist may be mistaken for a ganglion. In this series of 17 neurilemmomas, 6 were present in the forearm, and 11 were in the hand and wrist. There were 5 tumors in fingers, 1 in the thumb, 3 in the palm, and 2 in the wrist. In the forearm, 3 tumors involved the median nerve, 2 involved the ulnar nerve, and 1 arose from a small sensory branch of the radial nerve. Neurilemmomas arise from a benign proliferation of the Schwann cells and rarely disturb the function of the involved nerve. The tumors are well encapsulated and may be easily enucleated from the parent nerve. Resection of the involved nerve is seldom necessary except when small nerves are extensively involved.", "contents": "Neurilemmomas of the forearm and hand. Neurilemmoma is the most common tumor arising from peripheral nerves. Although infrequently encountered, it must be included in the differential diagnosis of soft tissue tumors. Because of its cystic consistency, a neurilemmoma in the hand or wrist may be mistaken for a ganglion. In this series of 17 neurilemmomas, 6 were present in the forearm, and 11 were in the hand and wrist. There were 5 tumors in fingers, 1 in the thumb, 3 in the palm, and 2 in the wrist. In the forearm, 3 tumors involved the median nerve, 2 involved the ulnar nerve, and 1 arose from a small sensory branch of the radial nerve. Neurilemmomas arise from a benign proliferation of the Schwann cells and rarely disturb the function of the involved nerve. The tumors are well encapsulated and may be easily enucleated from the parent nerve. Resection of the involved nerve is seldom necessary except when small nerves are extensively involved."} {"id": "PMID:1261111", "title": "Osteochondral fractures of the dome of the talus.", "content": "Fractures of the talor dome are uncommon and may elude diagnosis despite routine roentgenograms of injured ankles. Tomograms are helpful in localizing this lesion. Surgical removal of the osteochondral fragment is often indicated. Medial lesions may be inaccessible except by osteotomy of the medial malleolus which is then fixed with a bone screw. Lateral fragments are approached through anterolateral or posterolateral ankle incisions. Of 9 symptomatic ankles, 6 had satisfactory results following surgery. The other 3 were treated conservatively, one improved; two did not. One additional asymptomatic ankle remained so with no treatment. In one case the talus also contained an unusual cystic lesion; in another there was tarsal coalition.", "contents": "Osteochondral fractures of the dome of the talus. Fractures of the talor dome are uncommon and may elude diagnosis despite routine roentgenograms of injured ankles. Tomograms are helpful in localizing this lesion. Surgical removal of the osteochondral fragment is often indicated. Medial lesions may be inaccessible except by osteotomy of the medial malleolus which is then fixed with a bone screw. Lateral fragments are approached through anterolateral or posterolateral ankle incisions. Of 9 symptomatic ankles, 6 had satisfactory results following surgery. The other 3 were treated conservatively, one improved; two did not. One additional asymptomatic ankle remained so with no treatment. In one case the talus also contained an unusual cystic lesion; in another there was tarsal coalition."} {"id": "PMID:1261115", "title": "A fresh appraisal of tibial osteotomy for osteoarthritis of the knee.", "content": "A retrospective study was performed on 189 arthritic knees treated by tibial osteotomy at the Nuffield Orthopaedic Centre, Oxford, England to determine the quality of the results. The objective results were deduced from a numerical system of grading of pain, function, and movement, for 132 osteoarthritic knees. No statistical difference was found between high and low tibial osteotomies. Varus and male knees fared better than valgus and female knees. The result was significant only for the male varus group. Correction of the angular deformity had a profound influence on the results for varus but not for valgus knees. A joint tilt increase usually occurred and was associated with increased subluxation and instability in valgus knees but decreased or unchanged subluxation in varus knees. This was held to be an important cause of failure to achieve good results in valgus knees, and appeared to be an irremedial fault of tibial osteotomy.", "contents": "A fresh appraisal of tibial osteotomy for osteoarthritis of the knee. A retrospective study was performed on 189 arthritic knees treated by tibial osteotomy at the Nuffield Orthopaedic Centre, Oxford, England to determine the quality of the results. The objective results were deduced from a numerical system of grading of pain, function, and movement, for 132 osteoarthritic knees. No statistical difference was found between high and low tibial osteotomies. Varus and male knees fared better than valgus and female knees. The result was significant only for the male varus group. Correction of the angular deformity had a profound influence on the results for varus but not for valgus knees. A joint tilt increase usually occurred and was associated with increased subluxation and instability in valgus knees but decreased or unchanged subluxation in varus knees. This was held to be an important cause of failure to achieve good results in valgus knees, and appeared to be an irremedial fault of tibial osteotomy."} {"id": "PMID:1261116", "title": "Load testing of geometric and polycentric total knee replacements.", "content": "Static loading of implanted geometric and polycentric knee replacements was conducted in order to define fixation characteristics and load capabilities of the prostheses and the bone prostheses interface. Failures occurred in some specimens at load levels normally encountered across the knee joint during ambulation. Disruption of the tibial bone-cement interface and crushing of the tibial plateau were the modes of failure. There was no failure on the femoral side of the joint. The major determinants of stress failure suggested by this study were: (1) the tibial bone strength, (2) the design of the geometric and polycentric tibial component, and (3) method of component implantation.", "contents": "Load testing of geometric and polycentric total knee replacements. Static loading of implanted geometric and polycentric knee replacements was conducted in order to define fixation characteristics and load capabilities of the prostheses and the bone prostheses interface. Failures occurred in some specimens at load levels normally encountered across the knee joint during ambulation. Disruption of the tibial bone-cement interface and crushing of the tibial plateau were the modes of failure. There was no failure on the femoral side of the joint. The major determinants of stress failure suggested by this study were: (1) the tibial bone strength, (2) the design of the geometric and polycentric tibial component, and (3) method of component implantation."} {"id": "PMID:1261117", "title": "Intra-articular rheumatoid nodule of the knee joint.", "content": "A 44-year-old woman with a long-standing history of classical rheumatoid arthritis had an intra-articular rheumatoid nodule of the knee joint. The history, symptoms, and signs of this case were, however, almost identical to those cases previously reported. This entity has a classic presentation and distinct findings on examination which distinguish it from other intra-articular lesions of the knee.", "contents": "Intra-articular rheumatoid nodule of the knee joint. A 44-year-old woman with a long-standing history of classical rheumatoid arthritis had an intra-articular rheumatoid nodule of the knee joint. The history, symptoms, and signs of this case were, however, almost identical to those cases previously reported. This entity has a classic presentation and distinct findings on examination which distinguish it from other intra-articular lesions of the knee."} {"id": "PMID:1261119", "title": "Femoral neck fractures in young adults.", "content": "In 17 patients with femoral neck fractures who were between 15 and 40 years old the incidence of aseptic necrosis in patients followed more than 2 years was 18.7 per cent. The fracture was associated with other severe injuries in 40 per cent of the cases, probably reflecting the level of violence necessary to induce the fracture in young adults. Two of the 7 fractures treated with large-bore internal fixatives required secondary procedures to correct fracture displacement (this was not a complication with threaded devices). While the incidence of aseptic necrosis is no higher than that in other adult series, subsequent degenerative changes may supervene in many femoral neck fractures in this age group.", "contents": "Femoral neck fractures in young adults. In 17 patients with femoral neck fractures who were between 15 and 40 years old the incidence of aseptic necrosis in patients followed more than 2 years was 18.7 per cent. The fracture was associated with other severe injuries in 40 per cent of the cases, probably reflecting the level of violence necessary to induce the fracture in young adults. Two of the 7 fractures treated with large-bore internal fixatives required secondary procedures to correct fracture displacement (this was not a complication with threaded devices). While the incidence of aseptic necrosis is no higher than that in other adult series, subsequent degenerative changes may supervene in many femoral neck fractures in this age group."} {"id": "PMID:1261118", "title": "Prediction of thromboembolism following total hip replacement.", "content": "Obesity, edema in the legs before surgery, a history of deep venous thrombosis, varicose veins, and a diagnosis of osteoarthrosis were associated with an increased risk for postoperative thromboembolism. Selective administration of anticoagulants to high risk but not to low risk patients should result in a reduction in total mortality following surgery. It is therefore suggested that when deciding whether prophylactic anticoagulants should be administered to a patient, consideration should be given to that patient's likelihood of developing fatal pulmonary embolism if the anticoagulant is not given, compared to the potential reduction in his risk for fatal pulmonary embolism and the increase in risk for fatal bleeding complications if the anticoagulant is used.", "contents": "Prediction of thromboembolism following total hip replacement. Obesity, edema in the legs before surgery, a history of deep venous thrombosis, varicose veins, and a diagnosis of osteoarthrosis were associated with an increased risk for postoperative thromboembolism. Selective administration of anticoagulants to high risk but not to low risk patients should result in a reduction in total mortality following surgery. It is therefore suggested that when deciding whether prophylactic anticoagulants should be administered to a patient, consideration should be given to that patient's likelihood of developing fatal pulmonary embolism if the anticoagulant is not given, compared to the potential reduction in his risk for fatal pulmonary embolism and the increase in risk for fatal bleeding complications if the anticoagulant is used."} {"id": "PMID:1261121", "title": "The treatment of slipped upper femoral epiphysis by fibular grafting.", "content": "Fixation and early fusion of slipped upper femoral epiphysis can be achieved by the use of a fibular graft inserted through a lateral approach under X-ray control. Experience of the method in 18 hips has shown that fusion of the epiphysis had occurred in all cases by 19 weeks after operation whereas in 6 out of 13 cases treated with Moore's pins fusion was delayed beyond 6 months. The clinical and radiological results were comparable to those in cases treated with Moore's pins. There were no complications associated with the donor area. The method is suitable for the treatment of all stages of the condition with the exception of the most extreme degrees of chronic slip.", "contents": "The treatment of slipped upper femoral epiphysis by fibular grafting. Fixation and early fusion of slipped upper femoral epiphysis can be achieved by the use of a fibular graft inserted through a lateral approach under X-ray control. Experience of the method in 18 hips has shown that fusion of the epiphysis had occurred in all cases by 19 weeks after operation whereas in 6 out of 13 cases treated with Moore's pins fusion was delayed beyond 6 months. The clinical and radiological results were comparable to those in cases treated with Moore's pins. There were no complications associated with the donor area. The method is suitable for the treatment of all stages of the condition with the exception of the most extreme degrees of chronic slip."} {"id": "PMID:1261122", "title": "Central fractures of the acetabulum: a critical analysis and review of literature.", "content": "Central fracture of the acetabulum is an uncommon traumatic lesion of the pelvis that is usually best managed by conservative measures. Adequate roentgenographic evaluation and closed manipulation followed by skeletal traction is essential to attain and maintain congruity of the weight-bearing dome with the femoral head. Reduction should be maintained with traction continued uninterrupted for three months. Open reduction and internal fixation may be warranted if the actabular dome elements are of sufficient size for reconstruction of the pelvic wall. An early exercise program will improve and, as a rule, restore the range of hip joint motion. Protected weight-bearing may safely begin approximately three to four months post-injury.", "contents": "Central fractures of the acetabulum: a critical analysis and review of literature. Central fracture of the acetabulum is an uncommon traumatic lesion of the pelvis that is usually best managed by conservative measures. Adequate roentgenographic evaluation and closed manipulation followed by skeletal traction is essential to attain and maintain congruity of the weight-bearing dome with the femoral head. Reduction should be maintained with traction continued uninterrupted for three months. Open reduction and internal fixation may be warranted if the actabular dome elements are of sufficient size for reconstruction of the pelvic wall. An early exercise program will improve and, as a rule, restore the range of hip joint motion. Protected weight-bearing may safely begin approximately three to four months post-injury."} {"id": "PMID:1261123", "title": "Intramedullary nailing of femoral shaft fractures. Ten years' experience.", "content": "In 236 intramedullary nailings of femoral shaft fractures there was a 2 per cent deep infection rate, and a 7 per cent nonunion rate; 87 per cent had good primary healing; 42 per cent had further surgery after the initial nailing (two-thirds for removal of the nail). Statistical analysis of the data does not support the view that delayed internal fixation results in less nonunions. The 55 femurs nailed in the first 3 days had a nonunion rate of 11 per cent, as opposed to a 7 per cent postinjury rate for the entire series, a statistically significant increase in nonunions with the Vesely-Street nail. Intramedullary nailing has the following advantages over treatment with traction: shorter hospital stay; better knee motion; less angulation, and less shortening.", "contents": "Intramedullary nailing of femoral shaft fractures. Ten years' experience. In 236 intramedullary nailings of femoral shaft fractures there was a 2 per cent deep infection rate, and a 7 per cent nonunion rate; 87 per cent had good primary healing; 42 per cent had further surgery after the initial nailing (two-thirds for removal of the nail). Statistical analysis of the data does not support the view that delayed internal fixation results in less nonunions. The 55 femurs nailed in the first 3 days had a nonunion rate of 11 per cent, as opposed to a 7 per cent postinjury rate for the entire series, a statistically significant increase in nonunions with the Vesely-Street nail. Intramedullary nailing has the following advantages over treatment with traction: shorter hospital stay; better knee motion; less angulation, and less shortening."} {"id": "PMID:1261120", "title": "Leukocyte and serum alkaline phosphatase after hip arthroplasty, synovectomy of the knee and fracture.", "content": "The alkaline phosphatase in leukocytes (LAP) was measured in patients who had undergone various types of total arthroplasty of the hip, in patients who had undergone synovectomy and in whom tibial fractures had been treated conservatively. The LAP-Score increased rapidly and reached a maximum within a few days and returned to original levels after 14 days both after soft tissue trauma and skeletal trauma. The size of the maximal increase appears to vary only with the severity of the trauma. LAP was not found to be correlated with the increase in alkaline phosphatase in the serum. The increase in serum alkaline phosphatase occurred much later and decreased much slower and occurred only after skeletal trauma. The increase in alkaline phosphatase in the serum appears to vary with severity of skeletal trauma. A significant difference in LAP (P less than 0.05) was found between patients operated upon with total arthroplasty with success and those with deep infection. The difference between these two groups was, however, larger (P less than 0.01) regarding ESR and CRP.", "contents": "Leukocyte and serum alkaline phosphatase after hip arthroplasty, synovectomy of the knee and fracture. The alkaline phosphatase in leukocytes (LAP) was measured in patients who had undergone various types of total arthroplasty of the hip, in patients who had undergone synovectomy and in whom tibial fractures had been treated conservatively. The LAP-Score increased rapidly and reached a maximum within a few days and returned to original levels after 14 days both after soft tissue trauma and skeletal trauma. The size of the maximal increase appears to vary only with the severity of the trauma. LAP was not found to be correlated with the increase in alkaline phosphatase in the serum. The increase in serum alkaline phosphatase occurred much later and decreased much slower and occurred only after skeletal trauma. The increase in alkaline phosphatase in the serum appears to vary with severity of skeletal trauma. A significant difference in LAP (P less than 0.05) was found between patients operated upon with total arthroplasty with success and those with deep infection. The difference between these two groups was, however, larger (P less than 0.01) regarding ESR and CRP."} {"id": "PMID:1261127", "title": "Radiogrammetry at four bone sites in normal middle-aged women. their relation to each other, to calcium metabolism and to other biological variables.", "content": "In 167 women, ages 41 +/- 3.5 years, who constituted 80 per cent of nuns of this age group in the Omaha area, body dimensions and radiogrammetric indices were determined in (1) radius; (2) femoral shaft; (3) second metacarpal. Calcium, phosphorus and nitrogen balance were measured and calcium kinetics were calculated following oral and intravenous administration of two radioisotopes of calcium. The bone indices were significantly correlated to each other. The femoral diameter was correlated to all the kinetic variables, the radial to many, and the metacarpal to a few. All bone diameters were correlated to height, but only the femoral diameter to body weight. Femoral shaft diameter increased with time after the menopause, but was not correlated to age. There was no correlation between any bone variable and dietary calcium, absorbed calcium, or calcium balance. High dietary calcium was associated with lower bone resorption. There was no correlation between any bone variable and the urinary excretion of estrogens or 17 ketosteroids or 17 hydroxycorticosteroids. Although different bones of the skleton are qualitatively and quantitatively related, in survey work the femoral shaft should be included as a skeletal marker in addition to the second metacarpal. Femoral expansion occurs in women after the menopause. In normal women, dietary calcium is unrelated to skeletal indices.", "contents": "Radiogrammetry at four bone sites in normal middle-aged women. their relation to each other, to calcium metabolism and to other biological variables. In 167 women, ages 41 +/- 3.5 years, who constituted 80 per cent of nuns of this age group in the Omaha area, body dimensions and radiogrammetric indices were determined in (1) radius; (2) femoral shaft; (3) second metacarpal. Calcium, phosphorus and nitrogen balance were measured and calcium kinetics were calculated following oral and intravenous administration of two radioisotopes of calcium. The bone indices were significantly correlated to each other. The femoral diameter was correlated to all the kinetic variables, the radial to many, and the metacarpal to a few. All bone diameters were correlated to height, but only the femoral diameter to body weight. Femoral shaft diameter increased with time after the menopause, but was not correlated to age. There was no correlation between any bone variable and dietary calcium, absorbed calcium, or calcium balance. High dietary calcium was associated with lower bone resorption. There was no correlation between any bone variable and the urinary excretion of estrogens or 17 ketosteroids or 17 hydroxycorticosteroids. Although different bones of the skleton are qualitatively and quantitatively related, in survey work the femoral shaft should be included as a skeletal marker in addition to the second metacarpal. Femoral expansion occurs in women after the menopause. In normal women, dietary calcium is unrelated to skeletal indices."} {"id": "PMID:1261124", "title": "Complete rotation of the leg with associated deformities in poliomyelitis. A case report.", "content": "This is a report of a 24-year-old man with a heretofore unreported 180 degrees rotation deformity of the right leg on the thigh with the calf and heel in front and the patella and toes behind along with other associated deformities of both lower extremities in poliomyelitis. The right knee was flail and the popliteal pulsations could be felt anteriorly. The rotation deformity was successfully corrected by arthrodesis of the knee without any neurovascular damage. After correction of the other deformities, an erect posture was achieved by this patient.", "contents": "Complete rotation of the leg with associated deformities in poliomyelitis. A case report. This is a report of a 24-year-old man with a heretofore unreported 180 degrees rotation deformity of the right leg on the thigh with the calf and heel in front and the patella and toes behind along with other associated deformities of both lower extremities in poliomyelitis. The right knee was flail and the popliteal pulsations could be felt anteriorly. The rotation deformity was successfully corrected by arthrodesis of the knee without any neurovascular damage. After correction of the other deformities, an erect posture was achieved by this patient."} {"id": "PMID:1261125", "title": "Extremity gunshot wound and gunshot fracture in civilian practice.", "content": "The civilian gunshot wound is a low velocity injury. Temporary cavitation does not occur in the low velocity wound and damage is confined to the projectile pathway. Extensive debridement is not indicated for this injury. Surgical cleansing is used to convert the open, contaminated wound to a clean, closed wound. Reparative and definitive reconstruction then follow to restore form and function with minimized patient hazard.", "contents": "Extremity gunshot wound and gunshot fracture in civilian practice. The civilian gunshot wound is a low velocity injury. Temporary cavitation does not occur in the low velocity wound and damage is confined to the projectile pathway. Extensive debridement is not indicated for this injury. Surgical cleansing is used to convert the open, contaminated wound to a clean, closed wound. Reparative and definitive reconstruction then follow to restore form and function with minimized patient hazard."} {"id": "PMID:1261128", "title": "The lethal chondrodysplasias.", "content": "The lethal chondrodysplasias are a complex group of diseases of which little is known. Three disorders have been well characterized; achondrogenesis, thanatophoric dwarfism, and the lethal chondrodysplasias with polydactyly. Pathological studies of epiphyseal cartilage confirm the separateness of these diseases but further work is necessary to specify the limits of variations. In achondrogenesis, relatively minor forms differ greatly from the usual description. In the chondrodysplasias with polydactyly, skeletal involvement appears to vary from one case to another. Furthermore, we must pursue the genetic studies in thanatophoric dwarfism where the exact mode of inheritance is known.", "contents": "The lethal chondrodysplasias. The lethal chondrodysplasias are a complex group of diseases of which little is known. Three disorders have been well characterized; achondrogenesis, thanatophoric dwarfism, and the lethal chondrodysplasias with polydactyly. Pathological studies of epiphyseal cartilage confirm the separateness of these diseases but further work is necessary to specify the limits of variations. In achondrogenesis, relatively minor forms differ greatly from the usual description. In the chondrodysplasias with polydactyly, skeletal involvement appears to vary from one case to another. Furthermore, we must pursue the genetic studies in thanatophoric dwarfism where the exact mode of inheritance is known."} {"id": "PMID:1261130", "title": "The narrow lumbar spinal canal or lumbar spinal stenosis.", "content": "Narrow lumbar spinal canal or lumbar spinal stenosis is a not uncommon problem. Thirty-two patients with this disorder have been treated surgically at the Ochsner Medical Center between 1963 and 1973. The best method of diagnosis is a careful history and second is roentgenographic evidence, particularly the myelogram. The surgical treatment consists of total laminectomy and foraminotomy to insure complete decompression of the nerve roots. Eighteen patients have been followed from 14 to 44 months. Sixteen of the 18 considered their operations a success.", "contents": "The narrow lumbar spinal canal or lumbar spinal stenosis. Narrow lumbar spinal canal or lumbar spinal stenosis is a not uncommon problem. Thirty-two patients with this disorder have been treated surgically at the Ochsner Medical Center between 1963 and 1973. The best method of diagnosis is a careful history and second is roentgenographic evidence, particularly the myelogram. The surgical treatment consists of total laminectomy and foraminotomy to insure complete decompression of the nerve roots. Eighteen patients have been followed from 14 to 44 months. Sixteen of the 18 considered their operations a success."} {"id": "PMID:1261129", "title": "Growth following epiphyseal arrest. A simple method of calculation.", "content": "Four straight-line equations are derived from standard charts of growth remaining at normal epiphyses. Calculations made from these easily memorized formulas are a guide to the proper age for epiphysiodesis in children with leg length discrepancy.", "contents": "Growth following epiphyseal arrest. A simple method of calculation. Four straight-line equations are derived from standard charts of growth remaining at normal epiphyses. Calculations made from these easily memorized formulas are a guide to the proper age for epiphysiodesis in children with leg length discrepancy."} {"id": "PMID:1261126", "title": "Traumatic amputations. A vietnam experience.", "content": "Ninety-two acute combat amputations were performed in 70 casualities of the Vietnam conflict. In the 67 surviving patients with 83 stumps, primary closure was done in 24 limbs (30%) and delayed closure in 11 more. Closed cases were observed 2 weeks and no failures noted. In selected patients early suture of war amputations can be practiced with a satisfactory result.", "contents": "Traumatic amputations. A vietnam experience. Ninety-two acute combat amputations were performed in 70 casualities of the Vietnam conflict. In the 67 surviving patients with 83 stumps, primary closure was done in 24 limbs (30%) and delayed closure in 11 more. Closed cases were observed 2 weeks and no failures noted. In selected patients early suture of war amputations can be practiced with a satisfactory result."} {"id": "PMID:1261133", "title": "Revascularization of the femoral head. A clinical and experimental study.", "content": "Most large long-term follow-up studies of displaced femoral neck fractures treated by internal fixation show a 20-35 per cent late collapse of the femoral head. Clinical observations on factors such as age, time of collapse and isotopic evidence of bone turnover, seem to indicate that a strong revascularization potential may be more harmful than helpful. Experiments on completely devascularized femoral heads in dogs reveal that those allowed to revascularize showed creeping \"osteoporosis\" with partial or complete collapse in almost 50 per cent of the hips. Those canine femoral heads prevented from revascularizing showed much less osteoporosis and collapse, and the articular cartilage seemed to survive and function adequately for the 2 1/2 year duration of the experiment.", "contents": "Revascularization of the femoral head. A clinical and experimental study. Most large long-term follow-up studies of displaced femoral neck fractures treated by internal fixation show a 20-35 per cent late collapse of the femoral head. Clinical observations on factors such as age, time of collapse and isotopic evidence of bone turnover, seem to indicate that a strong revascularization potential may be more harmful than helpful. Experiments on completely devascularized femoral heads in dogs reveal that those allowed to revascularize showed creeping \"osteoporosis\" with partial or complete collapse in almost 50 per cent of the hips. Those canine femoral heads prevented from revascularizing showed much less osteoporosis and collapse, and the articular cartilage seemed to survive and function adequately for the 2 1/2 year duration of the experiment."} {"id": "PMID:1261141", "title": "How frequent is bacterial superinfection of the pharynx in infectious mononucleosis? Observations on incidence, recognition, and management with antibiotics.", "content": "Throat cultures from 133 patients with infectious mononucleosis were compared with cultures from 2,881 patients who were seen during the same period because of pharyngitis. Less than 3 per cent of the cultures from each group contained Group A beta hemolytic streptococci. The inflamed pharynx and necrotic tonsils of infectious mononucleosis are seldom subject to bacterial superinfection, either initially or during the course of the illness. There is no indication for routine use of antibiotics when infectious mononucleosis is diagnosed. Should, however, a throat culture indicate presence of a bacterial pathogen, any appropriate antibiotic except ampicillin may be used without increasing the incidence of skin rash.", "contents": "How frequent is bacterial superinfection of the pharynx in infectious mononucleosis? Observations on incidence, recognition, and management with antibiotics. Throat cultures from 133 patients with infectious mononucleosis were compared with cultures from 2,881 patients who were seen during the same period because of pharyngitis. Less than 3 per cent of the cultures from each group contained Group A beta hemolytic streptococci. The inflamed pharynx and necrotic tonsils of infectious mononucleosis are seldom subject to bacterial superinfection, either initially or during the course of the illness. There is no indication for routine use of antibiotics when infectious mononucleosis is diagnosed. Should, however, a throat culture indicate presence of a bacterial pathogen, any appropriate antibiotic except ampicillin may be used without increasing the incidence of skin rash."} {"id": "PMID:1261131", "title": "The effect of fluoride supplementation on the strength of osteopenic bone.", "content": "The strength of osteopenic bone from calcium deprived rats, quail and roosters was significantly reduced after fluoride supplementation. Using a device which measures torque, femurs from rats fed low calcium diets with 100 parts per million fluoride added to the water supply fractured at lower torque values than those values observed for rats fed a low calcium diet without fluoride. Fluoride administration and calcium restriction in adult roosters and young Japanese quail also resulted in a reduction in bone strength. This detrimental effect on bone strength must be considered in any therapeutic attempt to use fluoride ion to stimulate bone formation in osteopenic bone disorders.", "contents": "The effect of fluoride supplementation on the strength of osteopenic bone. The strength of osteopenic bone from calcium deprived rats, quail and roosters was significantly reduced after fluoride supplementation. Using a device which measures torque, femurs from rats fed low calcium diets with 100 parts per million fluoride added to the water supply fractured at lower torque values than those values observed for rats fed a low calcium diet without fluoride. Fluoride administration and calcium restriction in adult roosters and young Japanese quail also resulted in a reduction in bone strength. This detrimental effect on bone strength must be considered in any therapeutic attempt to use fluoride ion to stimulate bone formation in osteopenic bone disorders."} {"id": "PMID:1261132", "title": "The effect of methylmethacrylate on fracture healing.", "content": "Fractures were created in the femur of dogs by dividing the midshaft with an airdriven saw. Immobilization was achieved with a four-hole compression plate. No methylmethacrylate supplementation was used in the control groups. In the three experimental groups methylmethacrylate was added to the internal fixation by placing it on the endosteal, periosteal, and both surfaces of the bone. Healing of the fractures uniformly failed to occur when methylmethacrylate was apposed to both periosteal and endosteal regions. Histologic, fluorescent, and autoradiographic studies indicated that the bone surface in contact with methylmethacrylate was necrotic and did not incorporate tetracycline or Ca-45. New bone occurred only on the surface which was not in contact with methylmethacrylate.", "contents": "The effect of methylmethacrylate on fracture healing. Fractures were created in the femur of dogs by dividing the midshaft with an airdriven saw. Immobilization was achieved with a four-hole compression plate. No methylmethacrylate supplementation was used in the control groups. In the three experimental groups methylmethacrylate was added to the internal fixation by placing it on the endosteal, periosteal, and both surfaces of the bone. Healing of the fractures uniformly failed to occur when methylmethacrylate was apposed to both periosteal and endosteal regions. Histologic, fluorescent, and autoradiographic studies indicated that the bone surface in contact with methylmethacrylate was necrotic and did not incorporate tetracycline or Ca-45. New bone occurred only on the surface which was not in contact with methylmethacrylate."} {"id": "PMID:1261136", "title": "The epiphyseal dysplasias.", "content": "The epiphyseal dysplasias are a group of heterogeneous disorders characterized by defective or excessive bone formation in the secondary ossification centers of the tubular bones and sometimes the vertebrae. Most of them are caused by the defective action of mutant genes. Their pathogenesis is unknown. Differentiation of the various entities in this group is essential for the proper management and genetic counseling of the patients.", "contents": "The epiphyseal dysplasias. The epiphyseal dysplasias are a group of heterogeneous disorders characterized by defective or excessive bone formation in the secondary ossification centers of the tubular bones and sometimes the vertebrae. Most of them are caused by the defective action of mutant genes. Their pathogenesis is unknown. Differentiation of the various entities in this group is essential for the proper management and genetic counseling of the patients."} {"id": "PMID:1261139", "title": "Mesomelic skeletal dysplasias.", "content": "Mesomelic shortening of the extremities lends itself as a useful clinical and/or radiologic sign to characterize a group of hereditary bone dysplasias. Table 1 and Figure 4 are presented to facilitate the comparison between the many different types of mesomelic dwarfism. Differential diagnosis between these types is not difficult because of the specific bone changes and extraskeletal malformations present. As in many hereditary syndromes, however, there may be wide clinical variability within a single entity, and meticulous clinical and radiologic examination must be done to arrive at the correct diagnosis. Certain other forms of chondrodystrophies, such as achondroplasia, hypochondroplasia, pseudoachondroplasia and distrophic dwarfism, can be easily differentiated from the mesomelic dysplasias by their clinical features and skeletal radiographs. Nothing is known about the pathogenesis of the various forms of mesomelic dysplasias. There is no available specific treatment, although corrective surgery has benefited selected patients. The correct diagnosis is, however, important both for prognostication and accurate genetic counseling.", "contents": "Mesomelic skeletal dysplasias. Mesomelic shortening of the extremities lends itself as a useful clinical and/or radiologic sign to characterize a group of hereditary bone dysplasias. Table 1 and Figure 4 are presented to facilitate the comparison between the many different types of mesomelic dwarfism. Differential diagnosis between these types is not difficult because of the specific bone changes and extraskeletal malformations present. As in many hereditary syndromes, however, there may be wide clinical variability within a single entity, and meticulous clinical and radiologic examination must be done to arrive at the correct diagnosis. Certain other forms of chondrodystrophies, such as achondroplasia, hypochondroplasia, pseudoachondroplasia and distrophic dwarfism, can be easily differentiated from the mesomelic dysplasias by their clinical features and skeletal radiographs. Nothing is known about the pathogenesis of the various forms of mesomelic dysplasias. There is no available specific treatment, although corrective surgery has benefited selected patients. The correct diagnosis is, however, important both for prognostication and accurate genetic counseling."} {"id": "PMID:1261137", "title": "Diastrophic dwarfism.", "content": "Diastrophic dwarfism is an unusual variety of short-limb dwarfism characterized by the pathognomic triad of ear calcifications, hitch-hiker thumbs, and severe clubfoot. Other clinical features include joint contractures and subluxations, symphalagism of the fingers, kyphoscoliosis, hip dysplasia, and occasional cleft palate. Radiographic findings include flaring of the metaphyses of tubular bones and flattened epiphyses which appear late. The major orthopedic problem in diastrophic dwarfism is correction of the recalcitrant clubfoot deformity; cervical spine subluxation or kyphoscoliosis may also require intervention. This disorder is inherited as an autosomal recessive condition.", "contents": "Diastrophic dwarfism. Diastrophic dwarfism is an unusual variety of short-limb dwarfism characterized by the pathognomic triad of ear calcifications, hitch-hiker thumbs, and severe clubfoot. Other clinical features include joint contractures and subluxations, symphalagism of the fingers, kyphoscoliosis, hip dysplasia, and occasional cleft palate. Radiographic findings include flaring of the metaphyses of tubular bones and flattened epiphyses which appear late. The major orthopedic problem in diastrophic dwarfism is correction of the recalcitrant clubfoot deformity; cervical spine subluxation or kyphoscoliosis may also require intervention. This disorder is inherited as an autosomal recessive condition."} {"id": "PMID:1261138", "title": "Metaphyseal and spondylometaphyseal chondrodysplasias.", "content": "Diseases characterized by defective metaphyseal ossification, (metaphyseal chondrodysplasias) and defective spinal and metaphyseal ossification (spondylometaphyseal chondrodysplasias) constitute an important group of congenital intrinsic diseases of bones in which orthopedic treatment is of utmost interest. The most common types of metaphyseal chondrodysplasias (Jansen, Schmid, McKusick, and Metaphyseal Chondrodysplasia with Pancreatic Insufficiency and Neutropenia) and spondylometaphyseal chondrodysplasias (Kozlowski) have characteristic well-defined diagnostic features. The importance of proper diagnosis for practical reasons--appropriate medical and psychological treatment, professional training and genetic counseling--cannot be overemphasized. Elucidation of the pathogenesis in this group of diseases is bound to emerge from future histochemical and biochemical research.", "contents": "Metaphyseal and spondylometaphyseal chondrodysplasias. Diseases characterized by defective metaphyseal ossification, (metaphyseal chondrodysplasias) and defective spinal and metaphyseal ossification (spondylometaphyseal chondrodysplasias) constitute an important group of congenital intrinsic diseases of bones in which orthopedic treatment is of utmost interest. The most common types of metaphyseal chondrodysplasias (Jansen, Schmid, McKusick, and Metaphyseal Chondrodysplasia with Pancreatic Insufficiency and Neutropenia) and spondylometaphyseal chondrodysplasias (Kozlowski) have characteristic well-defined diagnostic features. The importance of proper diagnosis for practical reasons--appropriate medical and psychological treatment, professional training and genetic counseling--cannot be overemphasized. Elucidation of the pathogenesis in this group of diseases is bound to emerge from future histochemical and biochemical research."} {"id": "PMID:1261151", "title": "Phenytoin: pharmacokinetics and bioavailability.", "content": "The pharmacokinetics of a single 300-mg oral and intravenous and 14 daily 300-mg oral doses of phenytoin were studied in 6 healthy volunteers. The mean plasma elimination t1/2 was the same following intravenous (16.8 +/- 1.3 hr) and oral (17.1 +/- 1.5 hr) doses of phenytoin; however, following chronic oral administration, the t1/2 increased to 18.9 +/- 1.5 hr (p less than 0.05). The absolute bioavailability of an oral dosage form (Dilantin Kapseals) varied from 57.7 to 85.6% when based on the relationship between the corresponding single dose areas under the curve (AUCs). When based on the comparison of the AUC for multiple oral dosing with the single iv dose area, average bioavailability was 85.9% (71.8 to 106.3). Since the variation in the bioavailability and elimination of phenytoin does not allow accurate prediction of the steady-state plasma concentration, monitoring plasma levels may be of special importance.", "contents": "Phenytoin: pharmacokinetics and bioavailability. The pharmacokinetics of a single 300-mg oral and intravenous and 14 daily 300-mg oral doses of phenytoin were studied in 6 healthy volunteers. The mean plasma elimination t1/2 was the same following intravenous (16.8 +/- 1.3 hr) and oral (17.1 +/- 1.5 hr) doses of phenytoin; however, following chronic oral administration, the t1/2 increased to 18.9 +/- 1.5 hr (p less than 0.05). The absolute bioavailability of an oral dosage form (Dilantin Kapseals) varied from 57.7 to 85.6% when based on the relationship between the corresponding single dose areas under the curve (AUCs). When based on the comparison of the AUC for multiple oral dosing with the single iv dose area, average bioavailability was 85.9% (71.8 to 106.3). Since the variation in the bioavailability and elimination of phenytoin does not allow accurate prediction of the steady-state plasma concentration, monitoring plasma levels may be of special importance."} {"id": "PMID:1261152", "title": "Human serum and myocardium digoxin.", "content": "Linear correlation was demonstrated between serum digoxin and papillary muscle digoxin concentrations in patients undergoing mitral valve surgery. The mean ratio of myocardial tissue to serum digoxin concentrations was 6711. This result supports the use of serum digoxin as a guide for assessing the degree of digitalization under steady-state conditions.", "contents": "Human serum and myocardium digoxin. Linear correlation was demonstrated between serum digoxin and papillary muscle digoxin concentrations in patients undergoing mitral valve surgery. The mean ratio of myocardial tissue to serum digoxin concentrations was 6711. This result supports the use of serum digoxin as a guide for assessing the degree of digitalization under steady-state conditions."} {"id": "PMID:1261153", "title": "Spironolactone. I. Disposition and metabolism.", "content": "This study describes absorption, excretion, and metabolism of[20(-3)H]-spironolactone (SP) in 5 healthy men. After a single oral dose (200 mg + 200 muCi) of the drug given in alcoholic solution, the peak serum levels of the ethyl acetate-extractable tritium and the dethioacetylated metabolite canrenone were 763 +/- 400 ng/ml (mean +/- SD) and 415 +/- 145 ng/ml, respectively. These levels occurred within 3 hr. The serum half-life (T1/2) of the extractable materials was 37.3 +/- 6.53 hr. Canrenone levels declined in two phases. The T1/2 from 2.5 to 12 hr was 4.42 +/- 1.07 hr and from 12 to 72 hr was 16.8 +/- 2.75 hr. In the blood both SP and canrenone were confined largely in the plasma, and their protein binding exceeded 89% at concentrations of 550 and 710 ng/ml, respectively. In 5 days 31.6 +/- 5.87% of the radioactivity was excreted in the urine and 22.7 +/- 14.1% in the feces. Unchanged SP was not detected in the urine. The major urinary metabolites were canrenone (5.04 +/- 2.83% of dose), 6beta-OH-sulfoxide (5.21 +/- 0.93% of dose), and canrenoate ester glucuronide (6.2% of dose).", "contents": "Spironolactone. I. Disposition and metabolism. This study describes absorption, excretion, and metabolism of[20(-3)H]-spironolactone (SP) in 5 healthy men. After a single oral dose (200 mg + 200 muCi) of the drug given in alcoholic solution, the peak serum levels of the ethyl acetate-extractable tritium and the dethioacetylated metabolite canrenone were 763 +/- 400 ng/ml (mean +/- SD) and 415 +/- 145 ng/ml, respectively. These levels occurred within 3 hr. The serum half-life (T1/2) of the extractable materials was 37.3 +/- 6.53 hr. Canrenone levels declined in two phases. The T1/2 from 2.5 to 12 hr was 4.42 +/- 1.07 hr and from 12 to 72 hr was 16.8 +/- 2.75 hr. In the blood both SP and canrenone were confined largely in the plasma, and their protein binding exceeded 89% at concentrations of 550 and 710 ng/ml, respectively. In 5 days 31.6 +/- 5.87% of the radioactivity was excreted in the urine and 22.7 +/- 14.1% in the feces. Unchanged SP was not detected in the urine. The major urinary metabolites were canrenone (5.04 +/- 2.83% of dose), 6beta-OH-sulfoxide (5.21 +/- 0.93% of dose), and canrenoate ester glucuronide (6.2% of dose)."} {"id": "PMID:1261154", "title": "Spironolactone. II. Bioavailability.", "content": "The bioavailability of commercial 25-mg spironolactone tablets and a new tablet preparation containing 100 mg of the drug has been determined in 12 healthy male subjects. After a 200-mg oral dose of the drug given in a solution of polyethylene glycol-400, the peak plasma level of the dethioacetylated metabolite canrenone was 633 +/- 154 ng/ml (mean +/- SD) and was reached at 1.4 +/- 0.43 hr. This peak was higher and was achieved earlier than after either eight 25-mg tablets (480 +/- 155 ng/ml at 2.9 +/- 1.03 hr) or two 100-mg tablets (474 +/- 182 ng/ml at 3.0 +/- 1.37 hr). From the ratio of the 24-hr area under the plasma concentration-time curves, the bioavailabilities of the two tablet preparations relative to the solution were 99.6 +/- 18.2% and 92.1 +/- 22.9%, respectively. The amount of canrenone excreted in the urine by 48 hr was 4.48 +/- 1.26 mg (solution), 6.36 +/- 2.02 mg (eight 25-mg tablets), and 7.81 +/- 1.87 mg (two 100-mg tablets), representing 2% to 4% of the administered dose. It is concluded that urinary excretion of canrenone alone is not a reliable method for determining the bioavailability of spironolactone.", "contents": "Spironolactone. II. Bioavailability. The bioavailability of commercial 25-mg spironolactone tablets and a new tablet preparation containing 100 mg of the drug has been determined in 12 healthy male subjects. After a 200-mg oral dose of the drug given in a solution of polyethylene glycol-400, the peak plasma level of the dethioacetylated metabolite canrenone was 633 +/- 154 ng/ml (mean +/- SD) and was reached at 1.4 +/- 0.43 hr. This peak was higher and was achieved earlier than after either eight 25-mg tablets (480 +/- 155 ng/ml at 2.9 +/- 1.03 hr) or two 100-mg tablets (474 +/- 182 ng/ml at 3.0 +/- 1.37 hr). From the ratio of the 24-hr area under the plasma concentration-time curves, the bioavailabilities of the two tablet preparations relative to the solution were 99.6 +/- 18.2% and 92.1 +/- 22.9%, respectively. The amount of canrenone excreted in the urine by 48 hr was 4.48 +/- 1.26 mg (solution), 6.36 +/- 2.02 mg (eight 25-mg tablets), and 7.81 +/- 1.87 mg (two 100-mg tablets), representing 2% to 4% of the administered dose. It is concluded that urinary excretion of canrenone alone is not a reliable method for determining the bioavailability of spironolactone."} {"id": "PMID:1261155", "title": "Spironolactone. III. Canrenone--maximum and minimum steady-state plasma levels.", "content": "Steady-state plasma levels of canrenone have been examined in 23 healthy men who received repeated doses of spironolactone for 15 days. The dose regimens were 200 mg once a day and 50 mg 4 times a day. With both treatments the steady-state levels were reached after 3 to 4 days. With once-a-day treatment, the maximum and minimum steady-state levels were about 500 and 100 ng/ml, respectively. The minimum levels with treatment 4 times a day were about 200 ng/ml. The post steady-state half-life of canrenone with once-a-day treatment (19.2 +/- 6.57 hr) was longer (p less than 0.01) than the half-life obtained in the 4 times-a-day treatment (12.5 +/- 3.39 hr). The former half-life was similar to the log-linear phase half-life of canrenone in the single-dose studies.", "contents": "Spironolactone. III. Canrenone--maximum and minimum steady-state plasma levels. Steady-state plasma levels of canrenone have been examined in 23 healthy men who received repeated doses of spironolactone for 15 days. The dose regimens were 200 mg once a day and 50 mg 4 times a day. With both treatments the steady-state levels were reached after 3 to 4 days. With once-a-day treatment, the maximum and minimum steady-state levels were about 500 and 100 ng/ml, respectively. The minimum levels with treatment 4 times a day were about 200 ng/ml. The post steady-state half-life of canrenone with once-a-day treatment (19.2 +/- 6.57 hr) was longer (p less than 0.01) than the half-life obtained in the 4 times-a-day treatment (12.5 +/- 3.39 hr). The former half-life was similar to the log-linear phase half-life of canrenone in the single-dose studies."} {"id": "PMID:1261156", "title": "Lead intoxication: effects on cytochrome P-450-mediated hepatic oxidations.", "content": "Acute administration of lead to rats caused significant decreases in cytochrome P=450, ethylmorphine N-demethylase, and aniline hydroxylase activities and prolonged hexobarbital-induced sleeping times. However, chronic administration of lead to weanling rats caused no significant changes in hepatic cytochrome P-450 levels or in the microsomal oxidative enzymes over a 12-wk period. Eight patients exposed to lead in the process of burning through lead-painted steel structures for at least 3 mo showed marked effects of chronic lead intoxication on the erythropoietic system: inhibition of erythrocyte delta-aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of delta-aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary delta-aminolevulinic acid excretion. The plasma elimination rate of antipyrine, a drug primarily metabolized by hepatic microsomal enzymes, was determined in the 8 subjects prior to and following chelation therapy. In 7 of 8 subjects, chelation therapy shortened the antipyrine half-lives, but the effect was minimal. These studies show that chronic lead exposure results in significant hematopoietic inhibition of the heme biosynthetic pathway without causing significant changes in hepatic cytochrome P-450-associated enzymic activities.", "contents": "Lead intoxication: effects on cytochrome P-450-mediated hepatic oxidations. Acute administration of lead to rats caused significant decreases in cytochrome P=450, ethylmorphine N-demethylase, and aniline hydroxylase activities and prolonged hexobarbital-induced sleeping times. However, chronic administration of lead to weanling rats caused no significant changes in hepatic cytochrome P-450 levels or in the microsomal oxidative enzymes over a 12-wk period. Eight patients exposed to lead in the process of burning through lead-painted steel structures for at least 3 mo showed marked effects of chronic lead intoxication on the erythropoietic system: inhibition of erythrocyte delta-aminolevulinic acid dehydratase, increased erythrocyte protoporphyrin levels, and increased urinary excretion of delta-aminolevulinic acid. Chelation therapy greatly alleviated the inhibitory effects on dehydratase activity and decreased urinary delta-aminolevulinic acid excretion. The plasma elimination rate of antipyrine, a drug primarily metabolized by hepatic microsomal enzymes, was determined in the 8 subjects prior to and following chelation therapy. In 7 of 8 subjects, chelation therapy shortened the antipyrine half-lives, but the effect was minimal. These studies show that chronic lead exposure results in significant hematopoietic inhibition of the heme biosynthetic pathway without causing significant changes in hepatic cytochrome P-450-associated enzymic activities."} {"id": "PMID:1261157", "title": "N-Acetylprocainamide levels in patients with end-stage renal failure.", "content": "Serum concentrations of procainamide (PA) and N-acetylprocainamide (NAPA) were measured by fluorometry in subjects with normal renal function (n = 4) and in patients with end-stage renal failure (n = 3) after administration of 6.5 mg/kg of PA-HCl orally. Two subjects with normal renal function were rapid isonicotinic acid hydrazide (INH) acetylators and two were slow acetylators. The rapid acetylators had higher peak serum levels of NAPA (1.80 mug/ml) than the slow acetylators (0.40 mug/ml). Peak serum levels of PA were essentially identical in both. The half-life (T1/2) of PA was shorter, 2.5 hr, in the rapid acetylators than in the slow, 4.1 hr. The slope of the terminal portion of the blood time curve for NAPA was steeper (-0.087) for slow acetylators than for rapid (-0.078). These apparent differences between rapid and slow acetylators are not conclusive in themselves but tend to support the differences in acetylation previously reported. In the absence of renal function, the serum levels of PA were higher and the T1/2 prolonged. The serum levels of NAPA rose slowly and reached peak levels of 2 to 3 mug/ml and declined only with hemodialysis. In 3 patients measurable levels of NAPA were still present 78 hr (0.62 mug/ml), 94 hr (0.36 mug/ml), and 124 hr (0.70 mug/ml) after the single oral dose of PA. Clearance of NAPA during clinical hemodialysis was 48 +/- 10 cc/min compared to 75 +/- 12 ml/min for PA.", "contents": "N-Acetylprocainamide levels in patients with end-stage renal failure. Serum concentrations of procainamide (PA) and N-acetylprocainamide (NAPA) were measured by fluorometry in subjects with normal renal function (n = 4) and in patients with end-stage renal failure (n = 3) after administration of 6.5 mg/kg of PA-HCl orally. Two subjects with normal renal function were rapid isonicotinic acid hydrazide (INH) acetylators and two were slow acetylators. The rapid acetylators had higher peak serum levels of NAPA (1.80 mug/ml) than the slow acetylators (0.40 mug/ml). Peak serum levels of PA were essentially identical in both. The half-life (T1/2) of PA was shorter, 2.5 hr, in the rapid acetylators than in the slow, 4.1 hr. The slope of the terminal portion of the blood time curve for NAPA was steeper (-0.087) for slow acetylators than for rapid (-0.078). These apparent differences between rapid and slow acetylators are not conclusive in themselves but tend to support the differences in acetylation previously reported. In the absence of renal function, the serum levels of PA were higher and the T1/2 prolonged. The serum levels of NAPA rose slowly and reached peak levels of 2 to 3 mug/ml and declined only with hemodialysis. In 3 patients measurable levels of NAPA were still present 78 hr (0.62 mug/ml), 94 hr (0.36 mug/ml), and 124 hr (0.70 mug/ml) after the single oral dose of PA. Clearance of NAPA during clinical hemodialysis was 48 +/- 10 cc/min compared to 75 +/- 12 ml/min for PA."} {"id": "PMID:1261158", "title": "Blood ethanol concentrations during and following constant-rate intravenous infusion of alcohol.", "content": "Blood ethanol concentrations were determined in 7 subjects during and subsequent to a 2-hr constant-rate intravenous infusion of ethyl alcohol (8% v/v). Eight to 10 capillary blood samples were collected during the infusion and 10 to 21 samples were obtained after the infusion ceased. Thus, the total time course of blood ethanol concentrations in man was defined, both during and postinfusion. Blood ethanol concentration data from each of 6 subjects were fitted simultaneously to the two equations for the one-compartment open model with zero order input and Michaelis-Menten elimination kinetics. The average Vm[0.232 mg/(ml x hr)] and Km[0.0821 mg/ml] obtained fron these fittings correspond very closely with corresponding values estimated by the fitting of all the mean concentration-time data obtained following oral administration of 4 different doses of ethanol to 8 other fasting subjects in another study. A disproportionate increase in area under the concentration-time curve with increase in dose (gm/kg) was observed in a single subject who was infused with equal volumes of a 4% and an 8% (v/v) ethanol solution at the same constant rate.", "contents": "Blood ethanol concentrations during and following constant-rate intravenous infusion of alcohol. Blood ethanol concentrations were determined in 7 subjects during and subsequent to a 2-hr constant-rate intravenous infusion of ethyl alcohol (8% v/v). Eight to 10 capillary blood samples were collected during the infusion and 10 to 21 samples were obtained after the infusion ceased. Thus, the total time course of blood ethanol concentrations in man was defined, both during and postinfusion. Blood ethanol concentration data from each of 6 subjects were fitted simultaneously to the two equations for the one-compartment open model with zero order input and Michaelis-Menten elimination kinetics. The average Vm[0.232 mg/(ml x hr)] and Km[0.0821 mg/ml] obtained fron these fittings correspond very closely with corresponding values estimated by the fitting of all the mean concentration-time data obtained following oral administration of 4 different doses of ethanol to 8 other fasting subjects in another study. A disproportionate increase in area under the concentration-time curve with increase in dose (gm/kg) was observed in a single subject who was infused with equal volumes of a 4% and an 8% (v/v) ethanol solution at the same constant rate."} {"id": "PMID:1261159", "title": "Absorption and excretion of tolemetin in man.", "content": "Tolmetin, a nonsteroidal anti-inflammatory drug, is rapidly absorbed (10 to 20 min) and rapidly excreted (T1/2 congruent to 60 min) and shows a linear dose-plasma level response in the therapeutic dose range. Tolmetin does not affect its own metabolism on chronic administration. Tolmetin is displaced, in vitro, from plasma proteins by salicylic acid. This effect is reflected in minor changes in plasma levels and pharmacokinetic parameters when aspirin and tolmetin are coadministered.", "contents": "Absorption and excretion of tolemetin in man. Tolmetin, a nonsteroidal anti-inflammatory drug, is rapidly absorbed (10 to 20 min) and rapidly excreted (T1/2 congruent to 60 min) and shows a linear dose-plasma level response in the therapeutic dose range. Tolmetin does not affect its own metabolism on chronic administration. Tolmetin is displaced, in vitro, from plasma proteins by salicylic acid. This effect is reflected in minor changes in plasma levels and pharmacokinetic parameters when aspirin and tolmetin are coadministered."} {"id": "PMID:1261163", "title": "Tissue and erythrocyte distribution of digoxin in infants.", "content": "The distribution of digoxin in the myocardium, skeletal muscle, erythrocytes, and plasma (or serum) was studied in 19 infants. There was a linear relationship between myocardium and serum concentrations and no saturation was observed over the serum concentration range of 0.5-8.6 ng/ml. Myocardium uptake of digoxin was nearly twice as great in infants as in adults at any given serum concentration. Erythrocyte: plasma concentration ratios of digoxin were one-third smaller during digitalization than during maintenance digoxin therapy. The latter ratios were also three times greater in infants than found previously in adults. Their findings are consistent with a greater apparent volume of distribution of digoxin in infants and may partly explain the unusually large therapeutic doses needed in infants.", "contents": "Tissue and erythrocyte distribution of digoxin in infants. The distribution of digoxin in the myocardium, skeletal muscle, erythrocytes, and plasma (or serum) was studied in 19 infants. There was a linear relationship between myocardium and serum concentrations and no saturation was observed over the serum concentration range of 0.5-8.6 ng/ml. Myocardium uptake of digoxin was nearly twice as great in infants as in adults at any given serum concentration. Erythrocyte: plasma concentration ratios of digoxin were one-third smaller during digitalization than during maintenance digoxin therapy. The latter ratios were also three times greater in infants than found previously in adults. Their findings are consistent with a greater apparent volume of distribution of digoxin in infants and may partly explain the unusually large therapeutic doses needed in infants."} {"id": "PMID:1261164", "title": "Disposition of propoxyphene and propranolol in children.", "content": "The disposition of propoxyphene and propranolol was studied in children by means of two protocols which minimized the number of blood samples taken from each child. Propoxyphene and its metabolite, norpropoxyphene, were measured in two plasma samples obtained from different children at various times after a single oral dose. These data were pooled and a plasma concentration/time curve was obtained which was consistent with an average T 1/2 of 3.5 hr in this population. The bioavailability of tablets and a solution of propranolol was compared with a crossover design by obtaining plasma samples at the end of the dosage interval during chronic oral administration of various doses. No clear differences in the bioavailability of the two formulations could be detected. Both drugs showed marked interindividual differences in plasma concentrations following oral administration. These findings are consistent with the high hepatic extraction ratio and large presystemic (first pass) effect previously described in adults. The large individual variability supports the concept of monitoring plasma levels as an aid to therapy and demonstrates that the use of a weight-adjusted dose in children can be only an approximation for initial treatment.", "contents": "Disposition of propoxyphene and propranolol in children. The disposition of propoxyphene and propranolol was studied in children by means of two protocols which minimized the number of blood samples taken from each child. Propoxyphene and its metabolite, norpropoxyphene, were measured in two plasma samples obtained from different children at various times after a single oral dose. These data were pooled and a plasma concentration/time curve was obtained which was consistent with an average T 1/2 of 3.5 hr in this population. The bioavailability of tablets and a solution of propranolol was compared with a crossover design by obtaining plasma samples at the end of the dosage interval during chronic oral administration of various doses. No clear differences in the bioavailability of the two formulations could be detected. Both drugs showed marked interindividual differences in plasma concentrations following oral administration. These findings are consistent with the high hepatic extraction ratio and large presystemic (first pass) effect previously described in adults. The large individual variability supports the concept of monitoring plasma levels as an aid to therapy and demonstrates that the use of a weight-adjusted dose in children can be only an approximation for initial treatment."} {"id": "PMID:1261165", "title": "Maternal and neonatal elimination of amobarbital after treatment of the mother with barbiturates during late pregnancy.", "content": "Plasma half-lives of amobarbital were determined in newborn children of 10 mothers who had been treated with barbiturates for hypertension in pregnancy for 6 to 42 days prior to delivery. Five mothers had received amobarbital, 200 mg daily, and 5, phenobarbital, 60 to 180 mg daily. Half-lives in 7 of the babies ranged from 16.6 to 49.4 hr, comparable to those previously reported in babies of mothers who had received only a single dose of amobarbital. Thus there was no evidence of induction of amobarbital hydroxylation in these children. Two babies who had a greater than normal rise in serum bilirubin had longer half-lives (86.1 and 117.7 hr). In 1 baby whose mother had membranous glomerulonephritis, plasma amobarbital concentration did not significantly change over the period of the study.", "contents": "Maternal and neonatal elimination of amobarbital after treatment of the mother with barbiturates during late pregnancy. Plasma half-lives of amobarbital were determined in newborn children of 10 mothers who had been treated with barbiturates for hypertension in pregnancy for 6 to 42 days prior to delivery. Five mothers had received amobarbital, 200 mg daily, and 5, phenobarbital, 60 to 180 mg daily. Half-lives in 7 of the babies ranged from 16.6 to 49.4 hr, comparable to those previously reported in babies of mothers who had received only a single dose of amobarbital. Thus there was no evidence of induction of amobarbital hydroxylation in these children. Two babies who had a greater than normal rise in serum bilirubin had longer half-lives (86.1 and 117.7 hr). In 1 baby whose mother had membranous glomerulonephritis, plasma amobarbital concentration did not significantly change over the period of the study."} {"id": "PMID:1261166", "title": "Kinetics of carbamazepine and its 10,11-epoxide metabolite in children.", "content": "The plasma steady-state concentration of carbamazepine (CBZ) and its metabolite (carbamazepine-10,11-epoxide, CBZ-epoxide) was assessed in 43 children (2-15 yr) on CBZ (Tegretol) treatment. Twenty of the children received combined treatment with other anticonvulsant drugs simultaneously. The plasma concentrations were in the same range as had been found in adult patients on corresponding doses. Only a weak correlation was noted between dose and plasma CBZ concentration in the group of children on single-drug treatment, and there was no correlation in the group of children on combined drug regimen. Plasma levels of CBZ correlated with those of the metabolite. Children on combined treatment had lower CBZ concentration and, expressed as percent of the parent drug, the metabolite concentration was significantly higher than in children treated only with CBZ. In 2 children the plasma half-life of CBZ was estimated and found to be slightly shorter than has previously been reported in adults. In evaluating the plasma level-effect relationship of CBZ, the plasma concentration of the CBZ-epoxide should be measured simultaneously because of its anticonvulsant effect and interindividual variability.", "contents": "Kinetics of carbamazepine and its 10,11-epoxide metabolite in children. The plasma steady-state concentration of carbamazepine (CBZ) and its metabolite (carbamazepine-10,11-epoxide, CBZ-epoxide) was assessed in 43 children (2-15 yr) on CBZ (Tegretol) treatment. Twenty of the children received combined treatment with other anticonvulsant drugs simultaneously. The plasma concentrations were in the same range as had been found in adult patients on corresponding doses. Only a weak correlation was noted between dose and plasma CBZ concentration in the group of children on single-drug treatment, and there was no correlation in the group of children on combined drug regimen. Plasma levels of CBZ correlated with those of the metabolite. Children on combined treatment had lower CBZ concentration and, expressed as percent of the parent drug, the metabolite concentration was significantly higher than in children treated only with CBZ. In 2 children the plasma half-life of CBZ was estimated and found to be slightly shorter than has previously been reported in adults. In evaluating the plasma level-effect relationship of CBZ, the plasma concentration of the CBZ-epoxide should be measured simultaneously because of its anticonvulsant effect and interindividual variability."} {"id": "PMID:1261167", "title": "Acetaminophen elimination kinetics in neonates, children, and adults.", "content": "The elimination of acetaminophen (APAP) following an oral dose of 10 mg/kg in newborn infants, children, and adults was compared. Urinary excretion of unchanged APAP, APAP-sulfate, and APAP-glucuronide was complete within 30 hr at all ages. Higher percentages of the dose were excreted in the urine as APAP-sulfate in neonates (0-2 days old) and children (3-9 yr old) than in 12-yr old children and adults. A pharmacokinetic analysis indicated that the higher rate of APAP-sulfate formation in younger age groups apparently compensated for a deficiency in glucuronide formation. No dramatic age-related differences in the overall elimination rate constant for APAP were observed despite the quantitative changes in the metabolic pathways during early childhood.", "contents": "Acetaminophen elimination kinetics in neonates, children, and adults. The elimination of acetaminophen (APAP) following an oral dose of 10 mg/kg in newborn infants, children, and adults was compared. Urinary excretion of unchanged APAP, APAP-sulfate, and APAP-glucuronide was complete within 30 hr at all ages. Higher percentages of the dose were excreted in the urine as APAP-sulfate in neonates (0-2 days old) and children (3-9 yr old) than in 12-yr old children and adults. A pharmacokinetic analysis indicated that the higher rate of APAP-sulfate formation in younger age groups apparently compensated for a deficiency in glucuronide formation. No dramatic age-related differences in the overall elimination rate constant for APAP were observed despite the quantitative changes in the metabolic pathways during early childhood."} {"id": "PMID:1261168", "title": "Azidomorphine: subjective effects and suppression of morphine abstinence.", "content": "In man, azidomorphine, a new morphine congener, constricted pupils, produced morphine-like subjective effects and euphoria, and suppressed the morphine abstinence syndrome. Azidomorphine was 10 to 50 times as potent as morphine. It is concluded that in man azidomorphine is a typical morphine-like drug.", "contents": "Azidomorphine: subjective effects and suppression of morphine abstinence. In man, azidomorphine, a new morphine congener, constricted pupils, produced morphine-like subjective effects and euphoria, and suppressed the morphine abstinence syndrome. Azidomorphine was 10 to 50 times as potent as morphine. It is concluded that in man azidomorphine is a typical morphine-like drug."} {"id": "PMID:1261170", "title": "Pharmacokinetics of divided-dose ifosfamide.", "content": "The pharmacokinetics of a divided-dose schedule of ifosfamide was investigated in 3 patients given 1, 600 to 2,400 mg/sq m/day for 3 days, with a second course of treatment 21 days later. In contrast to the biexponential decay seen with single-dose ifosfamide (5,000 mg/sq m), data for divided low-dose plasma ifosfamide are best fitted by a monoexponential decay function compatible with a one-compartment open model. Plasma half-life for ifosfamide given in the divided-dose schedule was 6.9 hr, less than half that previously reported for high single-dose ifosfamide. Renal excretion rates and clearances for unchanged drug were similar in both schedules. The proportion of drug metabolized was larger and amount of unchanged drug excreted in the urine was smaller than after single large doses. The elimination constant for unchanged ifosfamide increased from day 1 to day 2 of treatment and remained relatively stable from day 2 to day 3 in the multidose regimen, with all parameters reverting to the pretreatment values 21days later.", "contents": "Pharmacokinetics of divided-dose ifosfamide. The pharmacokinetics of a divided-dose schedule of ifosfamide was investigated in 3 patients given 1, 600 to 2,400 mg/sq m/day for 3 days, with a second course of treatment 21 days later. In contrast to the biexponential decay seen with single-dose ifosfamide (5,000 mg/sq m), data for divided low-dose plasma ifosfamide are best fitted by a monoexponential decay function compatible with a one-compartment open model. Plasma half-life for ifosfamide given in the divided-dose schedule was 6.9 hr, less than half that previously reported for high single-dose ifosfamide. Renal excretion rates and clearances for unchanged drug were similar in both schedules. The proportion of drug metabolized was larger and amount of unchanged drug excreted in the urine was smaller than after single large doses. The elimination constant for unchanged ifosfamide increased from day 1 to day 2 of treatment and remained relatively stable from day 2 to day 3 in the multidose regimen, with all parameters reverting to the pretreatment values 21days later."} {"id": "PMID:1261171", "title": "Effects of acetylmethadol on plasma testosterone.", "content": "Plasma testosterone levels were measured in a group of 13 men maintained on acetylmethadol for treatment of opiate dependence. Prior to acetylmethadol administration, plasma testosterone levels were within normal adult ranges. Four hours following ingestion of acetylmethadol, plasma testosterone levels were significantly depressed and continued to fall 7-9 hr after drug administration. Plasma testosterone levels remained low 24-25 hr after the drug was taken, but, 48 hr following drug, plasma testosterone levels rose to values approximating those prior to drug. Depression of plasma testosterone levels following acetylmethadol ingestion was not only statistically but also biologically significant, since in many patients the levels were below the normal range for adult males.", "contents": "Effects of acetylmethadol on plasma testosterone. Plasma testosterone levels were measured in a group of 13 men maintained on acetylmethadol for treatment of opiate dependence. Prior to acetylmethadol administration, plasma testosterone levels were within normal adult ranges. Four hours following ingestion of acetylmethadol, plasma testosterone levels were significantly depressed and continued to fall 7-9 hr after drug administration. Plasma testosterone levels remained low 24-25 hr after the drug was taken, but, 48 hr following drug, plasma testosterone levels rose to values approximating those prior to drug. Depression of plasma testosterone levels following acetylmethadol ingestion was not only statistically but also biologically significant, since in many patients the levels were below the normal range for adult males."} {"id": "PMID:1261175", "title": "Restorative prosthetic mammaplasty in mastectomy for carcinoma and benign lesions.", "content": "It is possible to reconstruct the normal shape of the female breasts at the time of operation for carcinoma of the breast or benign lesions where the whole breast tissue is removed. This is done by the insertion of an inert silicone plastic prosthesis. This procedure avoids the mutilating effect normally associated with mastectomy. The criteria for this operation must be strictly applied if it is to be successful and if cure of the disease is not to be prejudiced. These principally involve local characteristics of the tumour and the nutrition of the skin flaps which will remain after the ablation procedure has been completed. The importance of strict adherence to the minutiae of the surgical technique is to be stressed. Failure to observe these will result in failure of the operation. It is also possible in cases with adequate skin to perform the operation as a secondary procedure where there has been an earlier mastectomy.", "contents": "Restorative prosthetic mammaplasty in mastectomy for carcinoma and benign lesions. It is possible to reconstruct the normal shape of the female breasts at the time of operation for carcinoma of the breast or benign lesions where the whole breast tissue is removed. This is done by the insertion of an inert silicone plastic prosthesis. This procedure avoids the mutilating effect normally associated with mastectomy. The criteria for this operation must be strictly applied if it is to be successful and if cure of the disease is not to be prejudiced. These principally involve local characteristics of the tumour and the nutrition of the skin flaps which will remain after the ablation procedure has been completed. The importance of strict adherence to the minutiae of the surgical technique is to be stressed. Failure to observe these will result in failure of the operation. It is also possible in cases with adequate skin to perform the operation as a secondary procedure where there has been an earlier mastectomy."} {"id": "PMID:1261176", "title": "Breast ptosis. Definition and treatment.", "content": "A definition of ptosis of the breast is given which permits differentiation of several kinds of defects to be made: pseudoptosis, partial ptosis, and true ptosis. In case of true ptosis, three degrees are described according to the nipple relation to the submammary fold and skin brassiere. An association with hypoplasia is described. The corrective techniques chosen are different according to the various types of ptosis and their possible association with various types of hypoplasia. The subpectoralis augmentation is used to insert the prosthesis in all cases.", "contents": "Breast ptosis. Definition and treatment. A definition of ptosis of the breast is given which permits differentiation of several kinds of defects to be made: pseudoptosis, partial ptosis, and true ptosis. In case of true ptosis, three degrees are described according to the nipple relation to the submammary fold and skin brassiere. An association with hypoplasia is described. The corrective techniques chosen are different according to the various types of ptosis and their possible association with various types of hypoplasia. The subpectoralis augmentation is used to insert the prosthesis in all cases."} {"id": "PMID:1261177", "title": "Subcutaneous mastectomy and fibrocystic disease of the breast.", "content": "There has been a considerable amount of data presented to implicate moderate to severe fibrocystic disease as a strong precursor of breast cancer. When a premenopausal woman with nodular breasts presents a biopsy examination characterized by sclerosing adenosis, intraductal hyperplasia and/or papillomatosis, microcystic disease, macrocystic disease, or lobular neoplasia, her malignant potential will be much greater than when these disease processes are absent. As a result, a prophylactic subcutaneous mastectomy is indicated and breast reconstruction with either an immediate or a delayed mammary prosthesis implantation should be performed.", "contents": "Subcutaneous mastectomy and fibrocystic disease of the breast. There has been a considerable amount of data presented to implicate moderate to severe fibrocystic disease as a strong precursor of breast cancer. When a premenopausal woman with nodular breasts presents a biopsy examination characterized by sclerosing adenosis, intraductal hyperplasia and/or papillomatosis, microcystic disease, macrocystic disease, or lobular neoplasia, her malignant potential will be much greater than when these disease processes are absent. As a result, a prophylactic subcutaneous mastectomy is indicated and breast reconstruction with either an immediate or a delayed mammary prosthesis implantation should be performed."} {"id": "PMID:1261178", "title": "The reduction mammaplasty--a combined technique.", "content": "The purposes of the reduction mammaplasty are: (1) the relief of the pain and discomfort of heavy, pendulous breasts; (2) the reduction is size of the breasts to achieve a normal and pleasing result with the brassiere in place and with clothing; (3) a reasonable and pleasing contour of the breasts from front and side, without the support of clothing or brassiere; (4) normally sensitive nipples which become erect on stimulation; (5) minimal apparent permanent scarring; (6) ideally intact ducts to the nipple; (7) a breast of size allowing for examination for breast masses. It is understandable that certain circumstances may forestall the achievement of some of these objectives, such as the presence of considerable amounts of diseased breast tissue, scars from resections of lesions of the breasts or from trauma, and massive hypertrophy of the breasts which may dictate a technique requiring free transplantation of nipples and areolae. However, several of the recent techniques allow for the achievements of these goals in a large percentage of cases. A combination of the better aspects of the techniques, with minor variations, may serve to deal even better and more consistently with the problem.", "contents": "The reduction mammaplasty--a combined technique. The purposes of the reduction mammaplasty are: (1) the relief of the pain and discomfort of heavy, pendulous breasts; (2) the reduction is size of the breasts to achieve a normal and pleasing result with the brassiere in place and with clothing; (3) a reasonable and pleasing contour of the breasts from front and side, without the support of clothing or brassiere; (4) normally sensitive nipples which become erect on stimulation; (5) minimal apparent permanent scarring; (6) ideally intact ducts to the nipple; (7) a breast of size allowing for examination for breast masses. It is understandable that certain circumstances may forestall the achievement of some of these objectives, such as the presence of considerable amounts of diseased breast tissue, scars from resections of lesions of the breasts or from trauma, and massive hypertrophy of the breasts which may dictate a technique requiring free transplantation of nipples and areolae. However, several of the recent techniques allow for the achievements of these goals in a large percentage of cases. A combination of the better aspects of the techniques, with minor variations, may serve to deal even better and more consistently with the problem."} {"id": "PMID:1261184", "title": "The augmentation-reduction mammaplasty.", "content": "The authors have presented a technique of augmentation mammaplasty with simultaneous treatment of glandular ptosis. They recommend this double procedure-one operation surgery for those with small and ptotic breasts, where treatment by a single procedure would not suffice to give an esthetically proportioned breast. This technique is simple, should pose no circulatory problems to the involved flaps, offers a short hospital stay and a fast recovery, and avoids two separate procedures.", "contents": "The augmentation-reduction mammaplasty. The authors have presented a technique of augmentation mammaplasty with simultaneous treatment of glandular ptosis. They recommend this double procedure-one operation surgery for those with small and ptotic breasts, where treatment by a single procedure would not suffice to give an esthetically proportioned breast. This technique is simple, should pose no circulatory problems to the involved flaps, offers a short hospital stay and a fast recovery, and avoids two separate procedures."} {"id": "PMID:1261186", "title": "Pros and cons of subpectoral implantation.", "content": "At the present time, there is no universally accepted surgical technique or prosthesis for augmenting breast volume. Each surgeon has to choose with regard to shape, consistency, and volume, according to his own conviction and respecting his patient's priorities. These priorities will vary with age, profession, sexual habits, and marital and social status. In order to get the best possible results, the plastic surgeon should be adept at alternative methods and should not be restricted to one technique or one prosthesis. Patients vary considerably so our methods should be diversified. Our subpectoral implantations have given us better results than our retroglandular ones, which have been performed during the same period of time and with the same prosthesis. Consequently, retropectoral implantation is still our preferred procedure. We think that this technique, with its proper indications, deserves wider application.", "contents": "Pros and cons of subpectoral implantation. At the present time, there is no universally accepted surgical technique or prosthesis for augmenting breast volume. Each surgeon has to choose with regard to shape, consistency, and volume, according to his own conviction and respecting his patient's priorities. These priorities will vary with age, profession, sexual habits, and marital and social status. In order to get the best possible results, the plastic surgeon should be adept at alternative methods and should not be restricted to one technique or one prosthesis. Patients vary considerably so our methods should be diversified. Our subpectoral implantations have given us better results than our retroglandular ones, which have been performed during the same period of time and with the same prosthesis. Consequently, retropectoral implantation is still our preferred procedure. We think that this technique, with its proper indications, deserves wider application."} {"id": "PMID:1261187", "title": "The tuberous breast.", "content": "The tuberous breast deformity cannot usually be corrected satisfactorily by standard augmentation mammaplasty or mastopexy. The two operative techniques described have been most helpful in dealing with this difficult problem. Anatomic differences in patients may permit or require modification of the techniques to correct a specific deformity. Although our experience to date with these techniques has been limited in number, we have been pleased with the postoperative results.", "contents": "The tuberous breast. The tuberous breast deformity cannot usually be corrected satisfactorily by standard augmentation mammaplasty or mastopexy. The two operative techniques described have been most helpful in dealing with this difficult problem. Anatomic differences in patients may permit or require modification of the techniques to correct a specific deformity. Although our experience to date with these techniques has been limited in number, we have been pleased with the postoperative results."} {"id": "PMID:1261188", "title": "The dermal brassiere mammaplasty.", "content": "With most methods, it is possible to obtain a good breast shape as an immediate postoperative result. The question is whether the satisfactory shape is permanent. The 7-year evaluation of the method described here has confirmed the safety of the procedure as well as the satisfactory conic breast shape it achieves. The result has proven to be lasting. The drooping of the gland is prevented by means of the dermopexy with firm fixation of the infra-areolar dermal pillar to the pectoral muscle. The method is indicated even for large hypertrophies as well as in cases of ptotic breasts of normal size and when combined with augmentation by silicone prosthesis for ptotic hypoplastic breasts. The careful pre-operative planning allows control of scar size with satisfactory quality since it is not exposed to undue tension. If these techniques are followed, only minor complications such as the occasional extrusion of a subcutaneous dermal stitch or, seldomly, cyst formation (as in all dermopexy methods), may occur.", "contents": "The dermal brassiere mammaplasty. With most methods, it is possible to obtain a good breast shape as an immediate postoperative result. The question is whether the satisfactory shape is permanent. The 7-year evaluation of the method described here has confirmed the safety of the procedure as well as the satisfactory conic breast shape it achieves. The result has proven to be lasting. The drooping of the gland is prevented by means of the dermopexy with firm fixation of the infra-areolar dermal pillar to the pectoral muscle. The method is indicated even for large hypertrophies as well as in cases of ptotic breasts of normal size and when combined with augmentation by silicone prosthesis for ptotic hypoplastic breasts. The careful pre-operative planning allows control of scar size with satisfactory quality since it is not exposed to undue tension. If these techniques are followed, only minor complications such as the occasional extrusion of a subcutaneous dermal stitch or, seldomly, cyst formation (as in all dermopexy methods), may occur."} {"id": "PMID:1261191", "title": "The double contrast enema in ulcerative and Crohn's colitis.", "content": "One hundred double contrast enema examinations using a colonic activator (veripaque in the preliminary cleansing enema and 51 conventional barium enema examinations without a preliminary veripaque enema have been performed on 94 patients with either ulcerative colitis or Crohn's disease of the colon. The severity of the disease at barium enema examinations has been graded and compared with the severity of the disease found at sigmoidoscopy. In the double contrast examination, there was agreement between the radiological and sigmoidoscopic findings in 77% of cases and a disagreement of one grade in the remaining 23% of cases. The double contrast enema demonstrated lesions in the colon proximal to the range of the sigmoidoscope of a greater severity than that seen at sigmoidoscopy in 30% of cases. It was not found possible to use the same grading method with the conventional enema, and unless frank ulceration is present, it is considered that the conventional enema is unreliable in assessing the state of the colonic mucosa. It is concluded that the double contrast enema, using a colonic activator in the preliminary cleansing enema, causes no greater risk of complications than either the conventional enema or sigmoidoscopy.", "contents": "The double contrast enema in ulcerative and Crohn's colitis. One hundred double contrast enema examinations using a colonic activator (veripaque in the preliminary cleansing enema and 51 conventional barium enema examinations without a preliminary veripaque enema have been performed on 94 patients with either ulcerative colitis or Crohn's disease of the colon. The severity of the disease at barium enema examinations has been graded and compared with the severity of the disease found at sigmoidoscopy. In the double contrast examination, there was agreement between the radiological and sigmoidoscopic findings in 77% of cases and a disagreement of one grade in the remaining 23% of cases. The double contrast enema demonstrated lesions in the colon proximal to the range of the sigmoidoscope of a greater severity than that seen at sigmoidoscopy in 30% of cases. It was not found possible to use the same grading method with the conventional enema, and unless frank ulceration is present, it is considered that the conventional enema is unreliable in assessing the state of the colonic mucosa. It is concluded that the double contrast enema, using a colonic activator in the preliminary cleansing enema, causes no greater risk of complications than either the conventional enema or sigmoidoscopy."} {"id": "PMID:1261192", "title": "Hepatodiaphragmatic interposition of the intestine (Chilaiditi's syndrome).", "content": "Hepatodiaphragmatic interposition of the intestine (HDI) is a common radiological finding in the normal population of Iran compared to Western countries (0.22% vs 0.02%). A high incidence of this finding was observed in patients with chronic lung disease (2.7%) and in women near term pregnancy (2.0%). A striking incidence of 22% was observed in patients with post-necrotic cirrhosis. Probable contributing factors are: (a) a redundant bowel with increased mobility, (b) an enlarged lower thoracic outlet in conditions such as pregnancy, emphysema, and cirrhosis with ascites, (c) an atrophic liver of post-necrotic cirrhosis, which leaves adequate space for intrusion of adjacent bowel segments. HDI of the bowel is generally an asymptomatic condition and its finding on a chest radiograph suggests atrophic cirrhosis of the liver.", "contents": "Hepatodiaphragmatic interposition of the intestine (Chilaiditi's syndrome). Hepatodiaphragmatic interposition of the intestine (HDI) is a common radiological finding in the normal population of Iran compared to Western countries (0.22% vs 0.02%). A high incidence of this finding was observed in patients with chronic lung disease (2.7%) and in women near term pregnancy (2.0%). A striking incidence of 22% was observed in patients with post-necrotic cirrhosis. Probable contributing factors are: (a) a redundant bowel with increased mobility, (b) an enlarged lower thoracic outlet in conditions such as pregnancy, emphysema, and cirrhosis with ascites, (c) an atrophic liver of post-necrotic cirrhosis, which leaves adequate space for intrusion of adjacent bowel segments. HDI of the bowel is generally an asymptomatic condition and its finding on a chest radiograph suggests atrophic cirrhosis of the liver."} {"id": "PMID:1261193", "title": "The value of the fatty meal in oral cholecystography.", "content": "In order to assess the value of the after fatty meal films, 232 oral cholecystograms were reviewed. Gallbladder opacification, duct visualisation, separation of gallbladder from overlying bowel gas shadows, and the demonstration of abnormalities were assessed from the pre-fatty meal films, and then again in conjunction with those taken after fat, when contraction was also assessed. Of the 200 examinations given the fatty meal, 132 were adjudged normal, 63 had gallstones, four had adenomyomatosis (one with stones), and two cholesterolosis. The post-fatty meal films, were found to be essential for the diagnosis of adenomyomatosis and cholesterolosis, and considered to be occasionally helpful in diagnosing small stones. They were of little value in assessing the biliary ducts, or separating the gallbladder from overlying bowel gas, and of no value in the diagnosis of functional biliary tract disorders.", "contents": "The value of the fatty meal in oral cholecystography. In order to assess the value of the after fatty meal films, 232 oral cholecystograms were reviewed. Gallbladder opacification, duct visualisation, separation of gallbladder from overlying bowel gas shadows, and the demonstration of abnormalities were assessed from the pre-fatty meal films, and then again in conjunction with those taken after fat, when contraction was also assessed. Of the 200 examinations given the fatty meal, 132 were adjudged normal, 63 had gallstones, four had adenomyomatosis (one with stones), and two cholesterolosis. The post-fatty meal films, were found to be essential for the diagnosis of adenomyomatosis and cholesterolosis, and considered to be occasionally helpful in diagnosing small stones. They were of little value in assessing the biliary ducts, or separating the gallbladder from overlying bowel gas, and of no value in the diagnosis of functional biliary tract disorders."} {"id": "PMID:1261194", "title": "Transient obstruction of the common bile duct following its exploration.", "content": "Failure of the contrast medium to enter the duodenum during the operative cholangiography following the common bile duct exploration and instrumentation may be caused by transient obstruction of the common bile duct. It is attributed to spasm and oedema of the sphincter choledochus of Boyden and not of the sphincter of Oddi. The knowledge of the possibility of the pseudo-obstruction of the common bile duct following its exploration may save the surgeon from unnecessary re-exploration and performing sphincterotomy or choledochoduodenostomy. The exploration is unnecessary if, during the common duct exploration, the dilators and the catheter passes easily into the duodenum and on the cholangiogram the obstructed area is smooth and there is no filling defect. A normal cholangiogram performed 8-10 days following the operation proves that the obstruction was transient and not caused by calculus stricture or tumour.", "contents": "Transient obstruction of the common bile duct following its exploration. Failure of the contrast medium to enter the duodenum during the operative cholangiography following the common bile duct exploration and instrumentation may be caused by transient obstruction of the common bile duct. It is attributed to spasm and oedema of the sphincter choledochus of Boyden and not of the sphincter of Oddi. The knowledge of the possibility of the pseudo-obstruction of the common bile duct following its exploration may save the surgeon from unnecessary re-exploration and performing sphincterotomy or choledochoduodenostomy. The exploration is unnecessary if, during the common duct exploration, the dilators and the catheter passes easily into the duodenum and on the cholangiogram the obstructed area is smooth and there is no filling defect. A normal cholangiogram performed 8-10 days following the operation proves that the obstruction was transient and not caused by calculus stricture or tumour."} {"id": "PMID:1261195", "title": "On the staging of breast carcinoma.", "content": "The implications of the new staging system for breast carcinoma proposed in 1973 by the International Union Against Cancer (UICC) in conjunction with the American Joint Committee on Cancer Staging and End Results (AJC) has been examined both in terms of staging distribution and the presentation of survival results as compared with the currently used International staging classification in a large consecutive series of patients referred for treatment between 1960-62. The new UICC/AJC system, if accepted, will require some 23% of cases at present Stage II (International) to be allocated to Stage I depending on a clinical assessment as to whether the nodes are involved or not. It will result in the reporting of increased survival rates for Stage I and Stage II disease, and this change is sufficiently large to be of statistical significance in Stage I disease at five and ten years.", "contents": "On the staging of breast carcinoma. The implications of the new staging system for breast carcinoma proposed in 1973 by the International Union Against Cancer (UICC) in conjunction with the American Joint Committee on Cancer Staging and End Results (AJC) has been examined both in terms of staging distribution and the presentation of survival results as compared with the currently used International staging classification in a large consecutive series of patients referred for treatment between 1960-62. The new UICC/AJC system, if accepted, will require some 23% of cases at present Stage II (International) to be allocated to Stage I depending on a clinical assessment as to whether the nodes are involved or not. It will result in the reporting of increased survival rates for Stage I and Stage II disease, and this change is sufficiently large to be of statistical significance in Stage I disease at five and ten years."} {"id": "PMID:1261196", "title": "Carcinoma of the male breast: report of a series of 88 cases.", "content": "A series of 88 cases of male breast cancer was compared with 241 cases of female breast cancer randomly selected from Departmental records. Cases of male breast cancer differed significantly from control female cases with regard to stage of the disease, age of onset and liability to the development of a second carcinoma. In 11 of the 88 cases (12.5%) of male breast cancer another primary malignant tumour developed. In seven instances the large bowel or rectum was the site of the other carcinoma. When correction was made for age and for the stage of the disease the prognosis of breast cancer in men and women was found to be similar. Only minor histological differences were found between male and female cases. Two of 54 cases examined for X-chromatin proved to be Barr-positive.", "contents": "Carcinoma of the male breast: report of a series of 88 cases. A series of 88 cases of male breast cancer was compared with 241 cases of female breast cancer randomly selected from Departmental records. Cases of male breast cancer differed significantly from control female cases with regard to stage of the disease, age of onset and liability to the development of a second carcinoma. In 11 of the 88 cases (12.5%) of male breast cancer another primary malignant tumour developed. In seven instances the large bowel or rectum was the site of the other carcinoma. When correction was made for age and for the stage of the disease the prognosis of breast cancer in men and women was found to be similar. Only minor histological differences were found between male and female cases. Two of 54 cases examined for X-chromatin proved to be Barr-positive."} {"id": "PMID:1261197", "title": "The effects of varied numbers of dose fractions on the tolerance of normal human skin.", "content": "The early and late radiation of small areas of normal human skin, included in the treatment of basal cell carcinomata, have been used to evaluate the validity of the fractions exponent of the Ellis NSD equation. Fraction numbers at the lower end of the range used clinically were investigated (3 ,7 and 10 fractions); total doses were calculated using an NSD of 1930 ret with a fractions exponent of 0.22. Time and hence the time exponent was constant (14 days). The patterns of increasing and declining early skin reaction, measured using an arbitrary numerical scoring system, and the proportion of treatment fields reaching skin tolerance were similar for the three treatment groups. The number of treated areas showing late normal tissue damage were also similar. These observations suggest that it is legitimate to apply the NSD hypothesis to treatments involving 3-10 fractions over an interval of 14 days. Of particular interest was the observation that the final cosmetic result and tumour cure was not significantly improved by treatment given as 10 fractions over that obtained with 3 fractions.", "contents": "The effects of varied numbers of dose fractions on the tolerance of normal human skin. The early and late radiation of small areas of normal human skin, included in the treatment of basal cell carcinomata, have been used to evaluate the validity of the fractions exponent of the Ellis NSD equation. Fraction numbers at the lower end of the range used clinically were investigated (3 ,7 and 10 fractions); total doses were calculated using an NSD of 1930 ret with a fractions exponent of 0.22. Time and hence the time exponent was constant (14 days). The patterns of increasing and declining early skin reaction, measured using an arbitrary numerical scoring system, and the proportion of treatment fields reaching skin tolerance were similar for the three treatment groups. The number of treated areas showing late normal tissue damage were also similar. These observations suggest that it is legitimate to apply the NSD hypothesis to treatments involving 3-10 fractions over an interval of 14 days. Of particular interest was the observation that the final cosmetic result and tumour cure was not significantly improved by treatment given as 10 fractions over that obtained with 3 fractions."} {"id": "PMID:1261198", "title": "Calculation of survival rates by the life table and other methods.", "content": "The last few years have seen the introduction of medical statistics into the curriculum for MB, BS and for the FFR. Also, an increasing number of clinical trials have considered statistics at the planning stage of the trial, rather than only at the end point. However, there is one particular aspect of medical statistics which has consistently been neglected, namely, technique in calculating survival rates for cancer patients. All too often, a direct method of calculation, see section 3.1, is used when a life table method would provide a better estimate. The life table, or actuarial method, was first described in a medical context by Greenwood (1926), and later by Merrell and Shulman (1955) and Cutler and Ederer (1958). It has however, not been explained in detail in a British journal. The objective of the present paper is to remedy, this fact so that it can be used more widely in the future in preference to a direct method.", "contents": "Calculation of survival rates by the life table and other methods. The last few years have seen the introduction of medical statistics into the curriculum for MB, BS and for the FFR. Also, an increasing number of clinical trials have considered statistics at the planning stage of the trial, rather than only at the end point. However, there is one particular aspect of medical statistics which has consistently been neglected, namely, technique in calculating survival rates for cancer patients. All too often, a direct method of calculation, see section 3.1, is used when a life table method would provide a better estimate. The life table, or actuarial method, was first described in a medical context by Greenwood (1926), and later by Merrell and Shulman (1955) and Cutler and Ederer (1958). It has however, not been explained in detail in a British journal. The objective of the present paper is to remedy, this fact so that it can be used more widely in the future in preference to a direct method."} {"id": "PMID:1261199", "title": "Treatment of connective tissue sarcomas by local excision followed by radioactive implant.", "content": "Thirty-two cases of connective tissue sarcoma were treated by local excision immediately followed by a radioactive implant, sometimes supplemented by external radiation. The method is effective in preventing local recurrence, and is particularly valuable for patients in whom persistent local recurrences following simple excision have occurred. The patient experiences little extra discomfort, and complications are unusual; hazard to staff is low. Long-term survival appears to be just as good in our series as in others in which radical surgery was used, the radical surgery has the disadvantages of greater operative morbidity and mortality, causes greater disfiguration, and may in any case be impossible for tumours in certain anatomical sites.", "contents": "Treatment of connective tissue sarcomas by local excision followed by radioactive implant. Thirty-two cases of connective tissue sarcoma were treated by local excision immediately followed by a radioactive implant, sometimes supplemented by external radiation. The method is effective in preventing local recurrence, and is particularly valuable for patients in whom persistent local recurrences following simple excision have occurred. The patient experiences little extra discomfort, and complications are unusual; hazard to staff is low. Long-term survival appears to be just as good in our series as in others in which radical surgery was used, the radical surgery has the disadvantages of greater operative morbidity and mortality, causes greater disfiguration, and may in any case be impossible for tumours in certain anatomical sites."} {"id": "PMID:1261201", "title": "Whole lung tomography in metastatic disease.", "content": "Because pulmonary metastases in patients with primary neoplasms have both therapeutic prognostic implications, a review was undertaken of 100 patients with primary neoplasms in whom whole lung tomography and chest roentgenography had been performed. Eight (20%) of 28 patients with solitary metastases on conventional films had more than one lesion on tomography. Due to the tomographic findings, therapy was altered in six of those eight. Two (3%) of 72 patients with normal chest roentgenograms had metastases visible on their tomograms. The data indicate the high value of whole lung tomography in determining therapy whenever a solitary metastasis is visible on conventional chest roentgenograms. The 3% pickup rate of metastases in patients with normal chest roentgenograms is less clear-cut but does suggest the contribution tomography can make in patients with potentially curable lesions.", "contents": "Whole lung tomography in metastatic disease. Because pulmonary metastases in patients with primary neoplasms have both therapeutic prognostic implications, a review was undertaken of 100 patients with primary neoplasms in whom whole lung tomography and chest roentgenography had been performed. Eight (20%) of 28 patients with solitary metastases on conventional films had more than one lesion on tomography. Due to the tomographic findings, therapy was altered in six of those eight. Two (3%) of 72 patients with normal chest roentgenograms had metastases visible on their tomograms. The data indicate the high value of whole lung tomography in determining therapy whenever a solitary metastasis is visible on conventional chest roentgenograms. The 3% pickup rate of metastases in patients with normal chest roentgenograms is less clear-cut but does suggest the contribution tomography can make in patients with potentially curable lesions."} {"id": "PMID:1261202", "title": "The lymphographic pattern in Hodgkin's disease: a correlation with the Rye histological classification.", "content": "Lymphograms performed before therapy in 51 patients with Hodgkin's disease have been analysed and the results related to the histology. Although a typical appearance for each histological type is described, it is not possible to predict the histological pattern from the radiographic appearances in an individual patient.", "contents": "The lymphographic pattern in Hodgkin's disease: a correlation with the Rye histological classification. Lymphograms performed before therapy in 51 patients with Hodgkin's disease have been analysed and the results related to the histology. Although a typical appearance for each histological type is described, it is not possible to predict the histological pattern from the radiographic appearances in an individual patient."} {"id": "PMID:1261203", "title": "The value of radiology in the idiopathic respiratory distress syndrome: a radiological and pathological correlation study.", "content": "The authors have reviewed the chest radiographs of 337 newborn babies who were referred for examination with respiratory distress. They have devised a system of grading of severity of hyaline membrane disease according to the degree of radiological changes and have been able to give a prognosis for each grade. The various complications of hyaline membrane disease have been reviewed. One hundred and sixteen autopsies were carried out and the radiological and pathological findings were correlated. A positive relationship in 82% of cases was found.", "contents": "The value of radiology in the idiopathic respiratory distress syndrome: a radiological and pathological correlation study. The authors have reviewed the chest radiographs of 337 newborn babies who were referred for examination with respiratory distress. They have devised a system of grading of severity of hyaline membrane disease according to the degree of radiological changes and have been able to give a prognosis for each grade. The various complications of hyaline membrane disease have been reviewed. One hundred and sixteen autopsies were carried out and the radiological and pathological findings were correlated. A positive relationship in 82% of cases was found."} {"id": "PMID:1261204", "title": "Double contrast upper gastrointestinal studies.", "content": "A technique for routine hyptonic double-contrast studies of the upper gastrointestinal tract is described. It is emphasized that, to achieve consistent success, the principles of the technique must be understood and applied at the time of the examination. The various factors producing the barium coating effect are described. Gas distension and bubble control are also described. Where applicable, the principles and projections are demonstrated by examples. Endoscopy with biopsy has added a new dimension of accuracy to diagnosis and is replacing barium studies for acute upper gastrointestinal haemorrhage. Accurate barium studies are important as a screening test of other symptomatology to select patients for further clarification by endoscopy.", "contents": "Double contrast upper gastrointestinal studies. A technique for routine hyptonic double-contrast studies of the upper gastrointestinal tract is described. It is emphasized that, to achieve consistent success, the principles of the technique must be understood and applied at the time of the examination. The various factors producing the barium coating effect are described. Gas distension and bubble control are also described. Where applicable, the principles and projections are demonstrated by examples. Endoscopy with biopsy has added a new dimension of accuracy to diagnosis and is replacing barium studies for acute upper gastrointestinal haemorrhage. Accurate barium studies are important as a screening test of other symptomatology to select patients for further clarification by endoscopy."} {"id": "PMID:1261205", "title": "Double contrast barium meal examination - a comparison of techniques for introducing gas.", "content": "A comparison made between five techniques for introducing additional gas to the stomach for double contrast barium examination showed effervescent tablets to be associated with significant improvement in gastric mucosal coating with significantly less bubble formation. A proprietary effervescent health salt on the other hand was associated with significantly greater bubble formation.", "contents": "Double contrast barium meal examination - a comparison of techniques for introducing gas. A comparison made between five techniques for introducing additional gas to the stomach for double contrast barium examination showed effervescent tablets to be associated with significant improvement in gastric mucosal coating with significantly less bubble formation. A proprietary effervescent health salt on the other hand was associated with significantly greater bubble formation."} {"id": "PMID:1261206", "title": "Post-heparin plasma lipoprotein lipase and hepatic lipase in normal subjects and in patients with hypertriglyceridaemia: correlations to sex, age and various parameters of triglyceride metabolism.", "content": "1. A selective immunochemical method was used to measure post-heparin plasma lipoprotein lipase and hepatic lipase activity in eighty-two normal subjects and in twenty patients with type IIb, IV or V hypertriglyceridaemia. In twenty-six normal subjects the activity of post-heparin plasma lipases was compared with the kinetic parameters of endogenous plasma triglyceride metabolism. 2. The activity of post-heparin lipoprotein lipase was significantly higher in normal females than in males, whereas the activity of hepatic lipase showed an opposite sex ratio. The activity of lipoprotein lipase decreased with age both in males and females, whereas no significant age variation was observed in the activity of hepatic lipase. 3. In normal subjects a highly significant negative correlation was present in both sexes between the activity of post-heparin plasma lipoprotein lipase and fasting serum triglyceride concentration, but not between the activity of post-heparin hepatic lipase and serum triglycerides. 4. The fractional removal rate of endogenous triglycerides was positively correlated to the activity of lipoprotein lipase but not to the activity of hepatic lipase. No relationship was found between the activities of post-heparin plasma lipases and the absolute turnover of serum triglycerides. 5. The mean activity of post-heparin plasma lipo-protein lipase was significantly lower in subjects with hyperprebetalipoproteinaemia than in normal individuals. However, many hypertriglyceridaemic patients had lipoprotein lipase within the normal range and there was no correlation between serum triglyceride concentration and the activity of post-heparin lipases. 6. All three patients with fasting chylomicronaemia had low post-heparin lipoprotein lipase activity. Several subjects with high post-heparin plasma hepatic lipase activity were present in the group with hyperprebetalipoproteinaemia, but the mean value of the hepatic lipase was not significantly different from normal.", "contents": "Post-heparin plasma lipoprotein lipase and hepatic lipase in normal subjects and in patients with hypertriglyceridaemia: correlations to sex, age and various parameters of triglyceride metabolism. 1. A selective immunochemical method was used to measure post-heparin plasma lipoprotein lipase and hepatic lipase activity in eighty-two normal subjects and in twenty patients with type IIb, IV or V hypertriglyceridaemia. In twenty-six normal subjects the activity of post-heparin plasma lipases was compared with the kinetic parameters of endogenous plasma triglyceride metabolism. 2. The activity of post-heparin lipoprotein lipase was significantly higher in normal females than in males, whereas the activity of hepatic lipase showed an opposite sex ratio. The activity of lipoprotein lipase decreased with age both in males and females, whereas no significant age variation was observed in the activity of hepatic lipase. 3. In normal subjects a highly significant negative correlation was present in both sexes between the activity of post-heparin plasma lipoprotein lipase and fasting serum triglyceride concentration, but not between the activity of post-heparin hepatic lipase and serum triglycerides. 4. The fractional removal rate of endogenous triglycerides was positively correlated to the activity of lipoprotein lipase but not to the activity of hepatic lipase. No relationship was found between the activities of post-heparin plasma lipases and the absolute turnover of serum triglycerides. 5. The mean activity of post-heparin plasma lipo-protein lipase was significantly lower in subjects with hyperprebetalipoproteinaemia than in normal individuals. However, many hypertriglyceridaemic patients had lipoprotein lipase within the normal range and there was no correlation between serum triglyceride concentration and the activity of post-heparin lipases. 6. All three patients with fasting chylomicronaemia had low post-heparin lipoprotein lipase activity. Several subjects with high post-heparin plasma hepatic lipase activity were present in the group with hyperprebetalipoproteinaemia, but the mean value of the hepatic lipase was not significantly different from normal."} {"id": "PMID:1261207", "title": "The clinical measurement of skeletal blood flow.", "content": "1. A new method for measurement of skeletal blood flow is described which depends on the complete extraction of 18F in a single passage through bone. 2. Plasma concentration and urinary excretion are measured over a 2 h period. The technique of impulse analysis is used to determine the initial transfer rate of 18F to bone and extravascular extracellular fluid (ECF). The ECF component is evaluated by using a second tracer (51 Cr-EDTA or 82Br) and the bone transfer rate obtained by difference. The 51Cr-EDTA data also provide an estimate of glomerular filtration rate and enable a correction to be applied for urinary bladder retention when necessary. 3. Duplicate measurements of skeletal blood flow in eight normal male volunteers gave mean flows between 4-4 and 5-9% of blood volume/min, or about 4 ml min-1 100 g-1 of bone. The variation between normal subjects was least when the results were expressed as % of blood volume/min rather than ml/min, ml min-1 kg-1 or ml min-1 1-73 m-2 body surface area. The precision of the technique was estimated to be 16-4%. 4. Addition of 1-5% random noise to the input data resulted in an uncertainty of 8-5% in the measurement of skeletal blood flow, suggesting that improved precision depends on closer control of physiological variables. 5. In six patients with severe untreated Paget's disease of bone, skeletal blood flow was 8-4-15-3% of blood volume/min. The increase was significant in all cases. 6. The absorbed radiation dose is low, so that the measurement can be repeated.", "contents": "The clinical measurement of skeletal blood flow. 1. A new method for measurement of skeletal blood flow is described which depends on the complete extraction of 18F in a single passage through bone. 2. Plasma concentration and urinary excretion are measured over a 2 h period. The technique of impulse analysis is used to determine the initial transfer rate of 18F to bone and extravascular extracellular fluid (ECF). The ECF component is evaluated by using a second tracer (51 Cr-EDTA or 82Br) and the bone transfer rate obtained by difference. The 51Cr-EDTA data also provide an estimate of glomerular filtration rate and enable a correction to be applied for urinary bladder retention when necessary. 3. Duplicate measurements of skeletal blood flow in eight normal male volunteers gave mean flows between 4-4 and 5-9% of blood volume/min, or about 4 ml min-1 100 g-1 of bone. The variation between normal subjects was least when the results were expressed as % of blood volume/min rather than ml/min, ml min-1 kg-1 or ml min-1 1-73 m-2 body surface area. The precision of the technique was estimated to be 16-4%. 4. Addition of 1-5% random noise to the input data resulted in an uncertainty of 8-5% in the measurement of skeletal blood flow, suggesting that improved precision depends on closer control of physiological variables. 5. In six patients with severe untreated Paget's disease of bone, skeletal blood flow was 8-4-15-3% of blood volume/min. The increase was significant in all cases. 6. The absorbed radiation dose is low, so that the measurement can be repeated."} {"id": "PMID:1261208", "title": "Suppression of the renin-aldosterone system in mild essential hypertension.", "content": "1. Suppression of the renin-aldosterone system by expansion of the extracellular fluid volume with extra sodium and mineralocorticoid for 6 days was studied in nine young men with very mild essential hypertension and in ten normotensive young men. 2. Plasma renin activity, measured both supine and after 45 degrees head-up tilt, and the renal excretion of aldosterone 18-glucuronide were similar in both groups. However, after expansion of the extracellular fluid volume, hypertensive patients showed much less suppression of both variables. 3. This difference persisted despite matching for an equivalent degree of expansion of the extracellular fluid volume as indexed by the change in body weight. 4. Administration of extra sodium and mineralocorticoid produced a greater proportional fall of renal aldosterone excretion than of plasma renin activity in both groups and this dissociation was significantly more marked in the hypertensive group. 5. We suggest that (i) a relative autonomy of the renin-aldosterone system may be relevant to the pathogenesis and/or perpetuation of essential hypertension and (ii) that the syndrome of low-renin hypertension is unlikely to be associated with \"mineralocorticoid\" excess.", "contents": "Suppression of the renin-aldosterone system in mild essential hypertension. 1. Suppression of the renin-aldosterone system by expansion of the extracellular fluid volume with extra sodium and mineralocorticoid for 6 days was studied in nine young men with very mild essential hypertension and in ten normotensive young men. 2. Plasma renin activity, measured both supine and after 45 degrees head-up tilt, and the renal excretion of aldosterone 18-glucuronide were similar in both groups. However, after expansion of the extracellular fluid volume, hypertensive patients showed much less suppression of both variables. 3. This difference persisted despite matching for an equivalent degree of expansion of the extracellular fluid volume as indexed by the change in body weight. 4. Administration of extra sodium and mineralocorticoid produced a greater proportional fall of renal aldosterone excretion than of plasma renin activity in both groups and this dissociation was significantly more marked in the hypertensive group. 5. We suggest that (i) a relative autonomy of the renin-aldosterone system may be relevant to the pathogenesis and/or perpetuation of essential hypertension and (ii) that the syndrome of low-renin hypertension is unlikely to be associated with \"mineralocorticoid\" excess."} {"id": "PMID:1261209", "title": "Polyuria associated with an antibody to vasopressin.", "content": "1. A patient with polyuria in whom diabetes insipidus had been diagnosed was treated with Pitressin. Resistance to this therapy developed after 18 months and a circulating antibody to vasopressin was then demonstrated. Withdrawal of therapy led to a fall in titre of the antibody and an increase in maximal urinary concentration. 2. The antibody to vasopressin was associated with the IgA fraction of the serum immunoglobulins and its characteristics are described.", "contents": "Polyuria associated with an antibody to vasopressin. 1. A patient with polyuria in whom diabetes insipidus had been diagnosed was treated with Pitressin. Resistance to this therapy developed after 18 months and a circulating antibody to vasopressin was then demonstrated. Withdrawal of therapy led to a fall in titre of the antibody and an increase in maximal urinary concentration. 2. The antibody to vasopressin was associated with the IgA fraction of the serum immunoglobulins and its characteristics are described."} {"id": "PMID:1261210", "title": "The influence of sodium intake on the pressor response to angiotensin II in the unanaesthetized rat.", "content": "1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium; the different diets were administered in various sequences. 2. In comparison with those from rats receiving a low sodium diet, the dose-response curves were displaced to the left on the high sodium diet, indicating a greater response to angiotensin, and this displacement persisted for a period of approximately 7 days after the diet was changed from high to low sodium. The dose-response curve subsequently shifted to the right when the low sodium diet was maintained for longer. 3. There was a negative correlation between the slope of the dose-response curve and the basal blood pressure in all groups; the correlation was significant in three out of the five different treatment groups. 4. Basal blood pressures were significantly raised in rats on the high sodium diet for 7 days. 5. A number of possible mechanisms have been considered to explain both the parallel shift of the dose-response curve and alteration in its slope. It is concluded that the observed findings are compatible with an action of sodium-loading on the sensitivity of the smooth muscle cell to angiotensin, on the resting of the renin-angiotensin system, on the rate of inactivation of angiotensin and on a change in initial length of the muscle fibre.", "contents": "The influence of sodium intake on the pressor response to angiotensin II in the unanaesthetized rat. 1. Dose-response curves for the pressor activity of angiotensin II have been determined in unanaesthetized rats receiving diets containing 2-5% (w/w) or 0-007% (w/w) sodium; the different diets were administered in various sequences. 2. In comparison with those from rats receiving a low sodium diet, the dose-response curves were displaced to the left on the high sodium diet, indicating a greater response to angiotensin, and this displacement persisted for a period of approximately 7 days after the diet was changed from high to low sodium. The dose-response curve subsequently shifted to the right when the low sodium diet was maintained for longer. 3. There was a negative correlation between the slope of the dose-response curve and the basal blood pressure in all groups; the correlation was significant in three out of the five different treatment groups. 4. Basal blood pressures were significantly raised in rats on the high sodium diet for 7 days. 5. A number of possible mechanisms have been considered to explain both the parallel shift of the dose-response curve and alteration in its slope. It is concluded that the observed findings are compatible with an action of sodium-loading on the sensitivity of the smooth muscle cell to angiotensin, on the resting of the renin-angiotensin system, on the rate of inactivation of angiotensin and on a change in initial length of the muscle fibre."} {"id": "PMID:1261211", "title": "Arterial oxygenation and carbon dioxide tensions in the production of hypoxic electroencephalographic changes in man.", "content": "1. To investigate the interaction of hypoxaemia and blood PCO2 in the production of cerebral hypoxia, we studied six healthy men in whom acute progressive hypoxia was induced by using a rebreathing technique, while the PCO2 was kept constant. 2. At least two blood PCO2 tensions were studied in each subject. Arterial oxygen saturation was monitored continuously by ear oximetry, calibrated for each subject with arterialized blood. The onset of cerebral hypoxia was identified by the appearance of frontal slow waves (less than 5 Hz) in the electroencephalogram (EEG), which was recorded continuously with the bipolar 10-20 electrode placement system. 3. All subjects developed frontal slow waves during at least one experiment: the EEG changes were similar both within and among subjects, irrespective of the blood PCO2 value. 4. The arterial oxygen saturation at which slow-wave activity first occurred showed a significant inverse linear relationship to the PCO2 value at which hypoxia was induced. 5. The results imply that more profound levels of hypoxia are tolerated with high PCO2 values than with normal or low PCO2 values before hypoxic EEG changes become evident. Thus if eucapnia is maintained, EEG changes suggestive of cerebral hypoxia are unlikely to occur if arterial oxygen saturation remains above 75%.", "contents": "Arterial oxygenation and carbon dioxide tensions in the production of hypoxic electroencephalographic changes in man. 1. To investigate the interaction of hypoxaemia and blood PCO2 in the production of cerebral hypoxia, we studied six healthy men in whom acute progressive hypoxia was induced by using a rebreathing technique, while the PCO2 was kept constant. 2. At least two blood PCO2 tensions were studied in each subject. Arterial oxygen saturation was monitored continuously by ear oximetry, calibrated for each subject with arterialized blood. The onset of cerebral hypoxia was identified by the appearance of frontal slow waves (less than 5 Hz) in the electroencephalogram (EEG), which was recorded continuously with the bipolar 10-20 electrode placement system. 3. All subjects developed frontal slow waves during at least one experiment: the EEG changes were similar both within and among subjects, irrespective of the blood PCO2 value. 4. The arterial oxygen saturation at which slow-wave activity first occurred showed a significant inverse linear relationship to the PCO2 value at which hypoxia was induced. 5. The results imply that more profound levels of hypoxia are tolerated with high PCO2 values than with normal or low PCO2 values before hypoxic EEG changes become evident. Thus if eucapnia is maintained, EEG changes suggestive of cerebral hypoxia are unlikely to occur if arterial oxygen saturation remains above 75%."} {"id": "PMID:1261212", "title": "Changes in the carotid body and the ventilatory response to hypoxia in chronically hypoxic rats.", "content": "1. Young rats were kept in a hypoxic chamber for 2-11 weeks and compared with littermate control animals. 2. The carotid bodies of the hypoxic rats enlarged, resembling those of men and animals living at high altitude. 3. Permanent blunting of the ventilatory response to hypoxia did not occur. Immediately on removal from the chamber, the rats, lightly anaesthetized, showed a smaller increase in ventilation during hypoxia than did control animals but this difference disappeared after 3 days' recovery in normoxia.", "contents": "Changes in the carotid body and the ventilatory response to hypoxia in chronically hypoxic rats. 1. Young rats were kept in a hypoxic chamber for 2-11 weeks and compared with littermate control animals. 2. The carotid bodies of the hypoxic rats enlarged, resembling those of men and animals living at high altitude. 3. Permanent blunting of the ventilatory response to hypoxia did not occur. Immediately on removal from the chamber, the rats, lightly anaesthetized, showed a smaller increase in ventilation during hypoxia than did control animals but this difference disappeared after 3 days' recovery in normoxia."} {"id": "PMID:1261213", "title": "Lipoprotein lipase and hormone-sensitive lipase activities in human subcutaneous lipomas: comparison with normal subcutaneous adipose tissue.", "content": "1. Lipoprotein lipase activity and hormone-sensitive lipase activity were investigated in subcutaneous lipomas removed from two patients and compared with the enzyme activities in subcutaneous adipose tissue from two normal subjects. 2. Confirmation was obtained of the presence of lipoprotein lipase activity in lipomas with an activity fifteen to forty-five times that in the two control samples. 3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline. However, compared with the non-lipomatous fat samples, these activities were lower, as was the magnitude of the lipolytic response to adrenaline plus theophylline. 4. The significance of these measurements of enzyme activity and their role in the pathogenesis of lipomas are briefly discussed.", "contents": "Lipoprotein lipase and hormone-sensitive lipase activities in human subcutaneous lipomas: comparison with normal subcutaneous adipose tissue. 1. Lipoprotein lipase activity and hormone-sensitive lipase activity were investigated in subcutaneous lipomas removed from two patients and compared with the enzyme activities in subcutaneous adipose tissue from two normal subjects. 2. Confirmation was obtained of the presence of lipoprotein lipase activity in lipomas with an activity fifteen to forty-five times that in the two control samples. 3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline. However, compared with the non-lipomatous fat samples, these activities were lower, as was the magnitude of the lipolytic response to adrenaline plus theophylline. 4. The significance of these measurements of enzyme activity and their role in the pathogenesis of lipomas are briefly discussed."} {"id": "PMID:1261266", "title": "Fibrocartilaginous emboli as the cause of ischemic myelopathy in a dog.", "content": "Acute hemiplegia and Horner's syndrome developed in a 6-year-old female black Labrador Retriever 24 hours after a day of exercise. Radiographic, cerebrospinal fluid, and electromyographic studies did not detect the site or nature of the suspected cervical lesion. The dog showed no improvement after evaluation for 5 days on corticosteroid and antibiotic therapy. Gross and microscopic examination revealed the presence of an ischemic infarct in the C6 segment of the cervical spinal cord and associated fibrocartilaginous emboli. The nature of the clinical signs and the pathologic findings in this case are similar to previous reports of human and canine cases.", "contents": "Fibrocartilaginous emboli as the cause of ischemic myelopathy in a dog. Acute hemiplegia and Horner's syndrome developed in a 6-year-old female black Labrador Retriever 24 hours after a day of exercise. Radiographic, cerebrospinal fluid, and electromyographic studies did not detect the site or nature of the suspected cervical lesion. The dog showed no improvement after evaluation for 5 days on corticosteroid and antibiotic therapy. Gross and microscopic examination revealed the presence of an ischemic infarct in the C6 segment of the cervical spinal cord and associated fibrocartilaginous emboli. The nature of the clinical signs and the pathologic findings in this case are similar to previous reports of human and canine cases."} {"id": "PMID:1261267", "title": "The immune response of rabbits to 3 strains of Mycoplasma agalactiae var. bovis isolated from mastitic bovine udders.", "content": "Rabbits were given 3 serologically-related trains of mycoplasma isolated from mastitic bovine udders. Growth inhibiting antibodies were not found. High-titered sera from each rabbit immunized with each strain developed at least 4 precipitin lines to each organism and at least one line of identity was demonstrated between the organisms. Significant indirect hemagglutination titers were found in all rabbits in 1 week, with titers reaching 1.0 X 10(5) to 3.3 X 10(5) in 4 to 6 weeks but despite continued intravenous antigenic stimulation, titers quickly fell to low levels thereafter.", "contents": "The immune response of rabbits to 3 strains of Mycoplasma agalactiae var. bovis isolated from mastitic bovine udders. Rabbits were given 3 serologically-related trains of mycoplasma isolated from mastitic bovine udders. Growth inhibiting antibodies were not found. High-titered sera from each rabbit immunized with each strain developed at least 4 precipitin lines to each organism and at least one line of identity was demonstrated between the organisms. Significant indirect hemagglutination titers were found in all rabbits in 1 week, with titers reaching 1.0 X 10(5) to 3.3 X 10(5) in 4 to 6 weeks but despite continued intravenous antigenic stimulation, titers quickly fell to low levels thereafter."} {"id": "PMID:1261268", "title": "Some biological and physical chemical properties of Erysipelothrix rhusiopathiae.", "content": "Fourteen strains of Erysipelothrix rhusiopathiae, representing extremes of host-range and world distribution, were examined for: 1) protein composition as determined by electrophoresis and electrofocus patterns, 2) guanine-cytosine mole ratios of their respective deoxyribonucleic acids, and 3) carbohydrate fermentation patterns. No correlation is apparent between any particular physical-chemical property and virulence in mice. The role the bacterial fragments play in the pathogenesis of a rabbit model of rheumatoid arthritis is discussed.", "contents": "Some biological and physical chemical properties of Erysipelothrix rhusiopathiae. Fourteen strains of Erysipelothrix rhusiopathiae, representing extremes of host-range and world distribution, were examined for: 1) protein composition as determined by electrophoresis and electrofocus patterns, 2) guanine-cytosine mole ratios of their respective deoxyribonucleic acids, and 3) carbohydrate fermentation patterns. No correlation is apparent between any particular physical-chemical property and virulence in mice. The role the bacterial fragments play in the pathogenesis of a rabbit model of rheumatoid arthritis is discussed."} {"id": "PMID:1261269", "title": "Effectiveness of certain teat dips and sanitizers in vitro and on teat skin against Mycoplasma agalactiae subsp. bovis.", "content": "Seven teat dip and sanitizer products were tested in vitro and in vivo for mycoplasmacidal activity against Mycoplasma agalactiae subsp. bovis (M. bovimastitidis). Most, but not all products tested appeared to kill the mycoplasma at satisfactory dilutions. These mycoplasma survived longer on teat skin during humid, rainy weather than during warm, dry weather. Acholeplasma laidlawii was frequently found on normal teat skin.", "contents": "Effectiveness of certain teat dips and sanitizers in vitro and on teat skin against Mycoplasma agalactiae subsp. bovis. Seven teat dip and sanitizer products were tested in vitro and in vivo for mycoplasmacidal activity against Mycoplasma agalactiae subsp. bovis (M. bovimastitidis). Most, but not all products tested appeared to kill the mycoplasma at satisfactory dilutions. These mycoplasma survived longer on teat skin during humid, rainy weather than during warm, dry weather. Acholeplasma laidlawii was frequently found on normal teat skin."} {"id": "PMID:1261270", "title": "Normal and abnormal xylose absorption in the horse.", "content": "The D-xylose absorption test was applied to clinically normal horses and to horses with signs of gastrointestinal disease. A dosage of 0.5 grams of xylose per kilogram of bodyweight was useful in detecting horses that absorbed the pentose abnormally. The clinical findings were correlated with gross and microscopic findings by biopsy and at necropsy. Gastrointestinal lesions associated with abnormal xylose absorption were classified as: 1) villous atrophy; 2) edema of the lamina propria or 3) necrosis of the lamina propria.", "contents": "Normal and abnormal xylose absorption in the horse. The D-xylose absorption test was applied to clinically normal horses and to horses with signs of gastrointestinal disease. A dosage of 0.5 grams of xylose per kilogram of bodyweight was useful in detecting horses that absorbed the pentose abnormally. The clinical findings were correlated with gross and microscopic findings by biopsy and at necropsy. Gastrointestinal lesions associated with abnormal xylose absorption were classified as: 1) villous atrophy; 2) edema of the lamina propria or 3) necrosis of the lamina propria."} {"id": "PMID:1261271", "title": "Reticuloendotheliosis in a dog.", "content": "A case of reticuloendotheliosis in a 7-year-old Gordon Setter is reported. Progressive weakness, debility, and diarrhea with melena were the presenting complaints. Clinical evaluation revealed splenomegaly, severe nonregenerative anemia, thrombocytopenia and leukopenia with many large blast cells in the peripheral blood. Necropsy revealed extensive involvement of bone marrow, spleen, liver, lymph nodes, kidneys, and adrenals. Gastric and duodenal ulcers were also present. The course, clinical findings and cellular characteristics of the case presented, closely resemble those reported in the syndrome of reticuloendotheliosis in cats.", "contents": "Reticuloendotheliosis in a dog. A case of reticuloendotheliosis in a 7-year-old Gordon Setter is reported. Progressive weakness, debility, and diarrhea with melena were the presenting complaints. Clinical evaluation revealed splenomegaly, severe nonregenerative anemia, thrombocytopenia and leukopenia with many large blast cells in the peripheral blood. Necropsy revealed extensive involvement of bone marrow, spleen, liver, lymph nodes, kidneys, and adrenals. Gastric and duodenal ulcers were also present. The course, clinical findings and cellular characteristics of the case presented, closely resemble those reported in the syndrome of reticuloendotheliosis in cats."} {"id": "PMID:1261272", "title": "Blood oxygenation and disturbances of the acid-base equilibrium in myocardial infarction.", "content": "In order to trace the changes in blood oxygenation and disturbances of the acid-base equilibrium in myocardial infarction, investigations were carried out in 136 patients aged 39-83 years. The values of blood oxygenation and the acid-base status were determined on the 1st, 2nd and 3rd day of the disease, and then after one, two and three to four weeks. Besides this, in 38 patients determinations were performed 3, 6, 9 and 12 months after the onset of the disease. The determinations were careied out with a micro-Astrup unit \"Radiometer\". It was demonstrated that hypoxaemia is very frequent complication of myocardial infarction since it appears in about 60% of cases of uncomplicated infarction. The intensity of hypoxaemia is greatest after 2-3 days. The intensity and duration of hypoxaemia depend on the clinical course of myocardial infarction. The most intense and longest persisting hypoxaemia was seen in patients with shock and/or acute left-ventricular failure. In nearly 25% of cases hypoxaemia was present even six months after the onset of the disease. Slight metabolic acidosis was observed on the 1st day of the disease in 37% of the cases, while severe metabolic acidosis was present in patients with shock and pulmonary oedema. Compensated metabolic acidosis was found in 50-60% of the cases during one year after myocardial infarction.", "contents": "Blood oxygenation and disturbances of the acid-base equilibrium in myocardial infarction. In order to trace the changes in blood oxygenation and disturbances of the acid-base equilibrium in myocardial infarction, investigations were carried out in 136 patients aged 39-83 years. The values of blood oxygenation and the acid-base status were determined on the 1st, 2nd and 3rd day of the disease, and then after one, two and three to four weeks. Besides this, in 38 patients determinations were performed 3, 6, 9 and 12 months after the onset of the disease. The determinations were careied out with a micro-Astrup unit \"Radiometer\". It was demonstrated that hypoxaemia is very frequent complication of myocardial infarction since it appears in about 60% of cases of uncomplicated infarction. The intensity of hypoxaemia is greatest after 2-3 days. The intensity and duration of hypoxaemia depend on the clinical course of myocardial infarction. The most intense and longest persisting hypoxaemia was seen in patients with shock and/or acute left-ventricular failure. In nearly 25% of cases hypoxaemia was present even six months after the onset of the disease. Slight metabolic acidosis was observed on the 1st day of the disease in 37% of the cases, while severe metabolic acidosis was present in patients with shock and pulmonary oedema. Compensated metabolic acidosis was found in 50-60% of the cases during one year after myocardial infarction."} {"id": "PMID:1261273", "title": "Changes in circadian sodium excretion in patients with essential hypertension and with renal artery stenosis.", "content": "In groups of healthy volunteers (C), patients with essential hypertension (EH), and patients with renal arterial stenosis (S), the following indicators were followed during 12-hour daytime (d) and nighttime (n) intervals: mean BP, endogenous creatinine clearance Ccr (GF), excretion of sodium (UNaV) and potassium (UKV), and their excretion fractions (CNa/GF and CK/GF). The d/n ratios of both UNaV and CNa/GF were significantly lowered in both groups of hypertensive persons as against the controls (1.5): in the EH, to 1.1, and in the S, to 0.8 on the average. Positively correlated with the value of the d/n ratio of the sodium excretion are the changes in the d/n ratios of water and solute excretions. The daytime potassium excretion exceeded the nighttime values in both groups of hypertensive persons. The d/n ratios of UKV and CK/GF were, however, significantly lowered as compared to the control values. These signs of disturbances of the circadian excretion of Na and K in EH and S exhibited no correlations with the values, or rhythms, of the mean BP, GF, or dietary uptake of sodium. The results do not indicate that the antihypertensive drugs used (alpha-methyldopa, dihydralazine, reserpine) would influence the circadian rhythm of Na excretion. The factors responsible for the disturbances of the circadian rhythms of Na and K excretion in hypertensive subjects have not yet been revealed.", "contents": "Changes in circadian sodium excretion in patients with essential hypertension and with renal artery stenosis. In groups of healthy volunteers (C), patients with essential hypertension (EH), and patients with renal arterial stenosis (S), the following indicators were followed during 12-hour daytime (d) and nighttime (n) intervals: mean BP, endogenous creatinine clearance Ccr (GF), excretion of sodium (UNaV) and potassium (UKV), and their excretion fractions (CNa/GF and CK/GF). The d/n ratios of both UNaV and CNa/GF were significantly lowered in both groups of hypertensive persons as against the controls (1.5): in the EH, to 1.1, and in the S, to 0.8 on the average. Positively correlated with the value of the d/n ratio of the sodium excretion are the changes in the d/n ratios of water and solute excretions. The daytime potassium excretion exceeded the nighttime values in both groups of hypertensive persons. The d/n ratios of UKV and CK/GF were, however, significantly lowered as compared to the control values. These signs of disturbances of the circadian excretion of Na and K in EH and S exhibited no correlations with the values, or rhythms, of the mean BP, GF, or dietary uptake of sodium. The results do not indicate that the antihypertensive drugs used (alpha-methyldopa, dihydralazine, reserpine) would influence the circadian rhythm of Na excretion. The factors responsible for the disturbances of the circadian rhythms of Na and K excretion in hypertensive subjects have not yet been revealed."} {"id": "PMID:1261274", "title": "Effects of propranolol on haemodynamic changes and gas exchange at rest, in orthostasis, and on exercise in patients with arterial hypertension.", "content": "The effects of propranolol on the circulation and respiration were studied in 38 patients with essential hypertension and symptomatic renal hypertension. The hypotensive effect of propranolol was associated with decrease in the cardiac index and heart rate; the peripheral vascular resistance moderately increased, and the circulating blood volume and haematocrit value showed no essential changes. Besides, a prolongation of the pre-ejection period, the decrease of intrasystolic index, an increase in the myocardial wall-tension index, and a retardation of the elevation rate of the intraventricular pressure were observed. After propranolol medication, on transition into the vertical position the heart rate showed a less marked acceleration; the remaining haemodynamic parameters changed in orthostasis as they had done before the treatment. After propranolol medication, on exercise the systolic and mean arterial pressures, heart rate, and cardiac output exhibited lesser increases than before the treatment, whereas the circulating blood volume, diasolic pressure, and peripheral vascular resistance increased just as they had done before the treatment. At rest, during propranolol medication there appeared a certain tendency to decreased oxygen uptake; in orthostasis the degree of increase in oxygen uptake did not change by the action of propranolol. Besides, propranolol did not alter the blood-plasma levels of lactic acid and pyruvate at rest and did not essentially change the oxygen uptake during exercise. The level of lactic acid and the lactate/pyruvate quotient in plasma during exercise increased slightly less after than without propranolol.", "contents": "Effects of propranolol on haemodynamic changes and gas exchange at rest, in orthostasis, and on exercise in patients with arterial hypertension. The effects of propranolol on the circulation and respiration were studied in 38 patients with essential hypertension and symptomatic renal hypertension. The hypotensive effect of propranolol was associated with decrease in the cardiac index and heart rate; the peripheral vascular resistance moderately increased, and the circulating blood volume and haematocrit value showed no essential changes. Besides, a prolongation of the pre-ejection period, the decrease of intrasystolic index, an increase in the myocardial wall-tension index, and a retardation of the elevation rate of the intraventricular pressure were observed. After propranolol medication, on transition into the vertical position the heart rate showed a less marked acceleration; the remaining haemodynamic parameters changed in orthostasis as they had done before the treatment. After propranolol medication, on exercise the systolic and mean arterial pressures, heart rate, and cardiac output exhibited lesser increases than before the treatment, whereas the circulating blood volume, diasolic pressure, and peripheral vascular resistance increased just as they had done before the treatment. At rest, during propranolol medication there appeared a certain tendency to decreased oxygen uptake; in orthostasis the degree of increase in oxygen uptake did not change by the action of propranolol. Besides, propranolol did not alter the blood-plasma levels of lactic acid and pyruvate at rest and did not essentially change the oxygen uptake during exercise. The level of lactic acid and the lactate/pyruvate quotient in plasma during exercise increased slightly less after than without propranolol."} {"id": "PMID:1261275", "title": "Myocardial blood flow in mitral valve disease and in primary congestive cardiomyopathy, and its relation to some haemodynamic indices.", "content": "Myocardial blood flow was estimated using the technique of selective xenon-133 solution injection into the coronary artery, in 20 patients with mitral stenosis, 8 patients with mitral insufficiency, 8 patients with primary cardiomyopathy, and in 7 healthy subjects. The mean value of myocardial blood flow in mitral stenosis (60.9 +/- 10.5 ml/min/100 g) and in mitral insufficiency (58.5 +/- 7.7) did not differ from the mean value obtained in the control group (66.0 +/- 9.1). On the other hand, myocardial blood flow in primary congestive cardiomyopathy was significantly diminished (54.1 +/- 8.6). Myocardial blood flow was also lowered in patients with class IV of heart failure (48.3 +/- 7.6), as compared to healthy subjects. A positive correlation was found between myocardial blood flow and the left ventricular work index (r = 0.48, p less than 0.05), as well as between myocardial blood flow and the right ventricular work index (r = 0.47, p less than 0.05). A weak correlation was noticed between myocardial blood flow and left ventricular end-diastolic pressure (r = 0.38, p less than 0.05), as well as between myocardial blood flow and right ventricular end-diastolic pressure (r = 0.34, p less than 0.05).", "contents": "Myocardial blood flow in mitral valve disease and in primary congestive cardiomyopathy, and its relation to some haemodynamic indices. Myocardial blood flow was estimated using the technique of selective xenon-133 solution injection into the coronary artery, in 20 patients with mitral stenosis, 8 patients with mitral insufficiency, 8 patients with primary cardiomyopathy, and in 7 healthy subjects. The mean value of myocardial blood flow in mitral stenosis (60.9 +/- 10.5 ml/min/100 g) and in mitral insufficiency (58.5 +/- 7.7) did not differ from the mean value obtained in the control group (66.0 +/- 9.1). On the other hand, myocardial blood flow in primary congestive cardiomyopathy was significantly diminished (54.1 +/- 8.6). Myocardial blood flow was also lowered in patients with class IV of heart failure (48.3 +/- 7.6), as compared to healthy subjects. A positive correlation was found between myocardial blood flow and the left ventricular work index (r = 0.48, p less than 0.05), as well as between myocardial blood flow and the right ventricular work index (r = 0.47, p less than 0.05). A weak correlation was noticed between myocardial blood flow and left ventricular end-diastolic pressure (r = 0.38, p less than 0.05), as well as between myocardial blood flow and right ventricular end-diastolic pressure (r = 0.34, p less than 0.05)."} {"id": "PMID:1261276", "title": "Some properties of adenosine deaminase from vascular smooth muscle and its inhibition by various vasodilators.", "content": "Because of some uncertainties still existing about the role of adenosine deaminase in the drug-influenced adenosine breakdown, the authors isolated this enzyme from vascular smooth muscle and studied the inhibition of its activity by some vasodilating drugs. The adenosine deaminase was purified 360-fold from bovine carotid artery by means of (NH4)2SO4-precipitation, heat treatment, and gel filtration. This enzyme behaves in a similar way as preparations of the same enzyme from other tissues in respect to pH-dependence and Michaelis constant. The vascular enzyme is inhibited by dipyridamole and trapymine in a competitive manner, hexobendine and lidoflazine are without any effect. The results lead to the conclusion that the inhibition of vascular adenosine deaminase does not constitute the sole cause of the adenosine-potentiating effect of the vasodilating drugs studied.", "contents": "Some properties of adenosine deaminase from vascular smooth muscle and its inhibition by various vasodilators. Because of some uncertainties still existing about the role of adenosine deaminase in the drug-influenced adenosine breakdown, the authors isolated this enzyme from vascular smooth muscle and studied the inhibition of its activity by some vasodilating drugs. The adenosine deaminase was purified 360-fold from bovine carotid artery by means of (NH4)2SO4-precipitation, heat treatment, and gel filtration. This enzyme behaves in a similar way as preparations of the same enzyme from other tissues in respect to pH-dependence and Michaelis constant. The vascular enzyme is inhibited by dipyridamole and trapymine in a competitive manner, hexobendine and lidoflazine are without any effect. The results lead to the conclusion that the inhibition of vascular adenosine deaminase does not constitute the sole cause of the adenosine-potentiating effect of the vasodilating drugs studied."} {"id": "PMID:1261277", "title": "Coronary circulation in experimental traumatic shock, and effect of some vasoactive agents on its parameters.", "content": "On 35 heparinized cats with experimental traumatic shock induced according to Cannon, changes in the coronary blood flow, produced by intravenous injections of noradrenaline, angiotensin, hydrocortisone, histamine, and serotonin, were studied. Traumatic shock was characterized by decreases in the coronary blood flow and organic oxygen uptake, despite a simultaneous decrease in the regional vascular resistance. Injections of noradrenaline (14-18 mug/kg) and angiotensin (29 mug/kg) induced, both in the initial normal state and in shock, increases in the coronary blood flow rate and in the regional oxygen uptake; an injection of hydrocortisone (7.1 mg/ml) produced similar effects in the normal state, but did not elevate the oxygen uptake in shock; an injection of histamine (32 mug/kg) had no effect on the coronary blood flow rate, but reduced the regional oxygen uptake both in the normal state and in shock; an injection of serotonin (30 mug/kg) exerted no major effects on the blood flow. The results obtained might serve as guidelines for pharmacological regulation of coronary circulation in shock.", "contents": "Coronary circulation in experimental traumatic shock, and effect of some vasoactive agents on its parameters. On 35 heparinized cats with experimental traumatic shock induced according to Cannon, changes in the coronary blood flow, produced by intravenous injections of noradrenaline, angiotensin, hydrocortisone, histamine, and serotonin, were studied. Traumatic shock was characterized by decreases in the coronary blood flow and organic oxygen uptake, despite a simultaneous decrease in the regional vascular resistance. Injections of noradrenaline (14-18 mug/kg) and angiotensin (29 mug/kg) induced, both in the initial normal state and in shock, increases in the coronary blood flow rate and in the regional oxygen uptake; an injection of hydrocortisone (7.1 mg/ml) produced similar effects in the normal state, but did not elevate the oxygen uptake in shock; an injection of histamine (32 mug/kg) had no effect on the coronary blood flow rate, but reduced the regional oxygen uptake both in the normal state and in shock; an injection of serotonin (30 mug/kg) exerted no major effects on the blood flow. The results obtained might serve as guidelines for pharmacological regulation of coronary circulation in shock."} {"id": "PMID:1261278", "title": "Distribution of the femoral circulation in living dogs.", "content": "The femoral circulation of living dogs was studied with plastic carbonized microspheres 50 and 200 micra in diameter, labeled with Yterbium169. The femoral blood flow is distributed in the following way: 35% of the particles 50 micra in diameter went to muscle, 45% of the same particles went to skin and 20% to bone. When the particles were 200 micra in diameter 16% went to muscle, 65% to skin and 19% to bone.", "contents": "Distribution of the femoral circulation in living dogs. The femoral circulation of living dogs was studied with plastic carbonized microspheres 50 and 200 micra in diameter, labeled with Yterbium169. The femoral blood flow is distributed in the following way: 35% of the particles 50 micra in diameter went to muscle, 45% of the same particles went to skin and 20% to bone. When the particles were 200 micra in diameter 16% went to muscle, 65% to skin and 19% to bone."} {"id": "PMID:1261279", "title": "Speech and memory assessment in psychomotor epileptics.", "content": "Thirty post-lobectomy patients operated on for relief of seizures due to temporal lobe epilepsy and six patients who had had implantation of depth electrodes only were assessed in terms of their speech and memory abilities. The results from two subtests of the Boston Diagnostic Aphasia Examination show no significant group differences on speech tests. On the other hand, patients with left or dominant temporal lobectomies showed a greater memory deficit than those operated upon on the right or non-dominant side. This difference was apparent on tests of both recent verbal memory and long-term memory.", "contents": "Speech and memory assessment in psychomotor epileptics. Thirty post-lobectomy patients operated on for relief of seizures due to temporal lobe epilepsy and six patients who had had implantation of depth electrodes only were assessed in terms of their speech and memory abilities. The results from two subtests of the Boston Diagnostic Aphasia Examination show no significant group differences on speech tests. On the other hand, patients with left or dominant temporal lobectomies showed a greater memory deficit than those operated upon on the right or non-dominant side. This difference was apparent on tests of both recent verbal memory and long-term memory."} {"id": "PMID:1261280", "title": "Recognition memory in amnesic patients: effect of temporal context and familiarity of material.", "content": "In Experiment I recognition memory for pictures, high frequency words and low frequency words was examined in Korsakoff patients and alcoholic controls at retention intervals of 10 minutes, one week and seven weeks. Korsakoffs showed (1) surprisingly good recognition of pictures and low frequency words, scoring well above chance even at the longest retention interval; (2) no evidence of a faster than normal rate of forgetting. In experiment II the familiarity of pictures was varied in such a way that correct recognition involved either (a) explicit decisions as to whether items were seen 10 minutes or 24 hours previously or (b)decisions as to whether items had ever been seen before. Korsakoffs were severely impaired in making the first type of discrimination but had little difficulty with the second type. It is suggested that the primary defect in amnesia may concern contextual memory rather than memory for items as such.", "contents": "Recognition memory in amnesic patients: effect of temporal context and familiarity of material. In Experiment I recognition memory for pictures, high frequency words and low frequency words was examined in Korsakoff patients and alcoholic controls at retention intervals of 10 minutes, one week and seven weeks. Korsakoffs showed (1) surprisingly good recognition of pictures and low frequency words, scoring well above chance even at the longest retention interval; (2) no evidence of a faster than normal rate of forgetting. In experiment II the familiarity of pictures was varied in such a way that correct recognition involved either (a) explicit decisions as to whether items were seen 10 minutes or 24 hours previously or (b)decisions as to whether items had ever been seen before. Korsakoffs were severely impaired in making the first type of discrimination but had little difficulty with the second type. It is suggested that the primary defect in amnesia may concern contextual memory rather than memory for items as such."} {"id": "PMID:1261281", "title": "Interset variability on the raven coloured progressive matrices as an indicator of specific ability deficit in brain-lesioned patients.", "content": "Patients with right cerebral lesions were found to have lower RCPM scores than a matched group of patients with left lesions. Analysis of interset patterns of performance demonstrated relatively greater difficulty for right lesion patients, especially those with posterior lesions on the Ab set. The findings were interpreted in terms of the abilities that Raven maintains underly test performance.", "contents": "Interset variability on the raven coloured progressive matrices as an indicator of specific ability deficit in brain-lesioned patients. Patients with right cerebral lesions were found to have lower RCPM scores than a matched group of patients with left lesions. Analysis of interset patterns of performance demonstrated relatively greater difficulty for right lesion patients, especially those with posterior lesions on the Ab set. The findings were interpreted in terms of the abilities that Raven maintains underly test performance."} {"id": "PMID:1261282", "title": "Visual field recognition memory for right-handed females as a function of familial handedness.", "content": "Recognition memory for nonsense words presented vertically and unilaterally in the left and right visual fields was investigated in right-handed females as a function of the memory interval and familial handedness. The subject decided whether another nonsense word presented in central vision after memory intervals of 0, 5, or 10 sec. was the same as the stimulus word. The exposure duration producing a recognition accuracy of about 75% for each subject was employed and ranged from 5 to 28 msec. Right-handed females with only right-handed family members demonstrated right visual field superiorities indicative of a slight left hemisphere specialization for memory but not for reception of verbal material. Field superiorities obtained for right-handed females with a left-handed parent or sibling were not significant. In general, less complete lateralization of linguistic function in females was indicated and the importance of familial handedness in cerebral asymmetry of function was confirmed.", "contents": "Visual field recognition memory for right-handed females as a function of familial handedness. Recognition memory for nonsense words presented vertically and unilaterally in the left and right visual fields was investigated in right-handed females as a function of the memory interval and familial handedness. The subject decided whether another nonsense word presented in central vision after memory intervals of 0, 5, or 10 sec. was the same as the stimulus word. The exposure duration producing a recognition accuracy of about 75% for each subject was employed and ranged from 5 to 28 msec. Right-handed females with only right-handed family members demonstrated right visual field superiorities indicative of a slight left hemisphere specialization for memory but not for reception of verbal material. Field superiorities obtained for right-handed females with a left-handed parent or sibling were not significant. In general, less complete lateralization of linguistic function in females was indicated and the importance of familial handedness in cerebral asymmetry of function was confirmed."} {"id": "PMID:1261283", "title": "Some relations of grammar and lexicon in aphasia.", "content": "A new form of a Sentence Order Test was applied to a group of Broca's, Wernicke's and total aphasics. Sentences cut into three movable cards should be put together. Some of the sentences could be arranged in two different ways. Broca's aphasics prefered to order the parts according to a logical string of lexical items neglecting the grammatical errors. Wernicke's aphasics arranged the material according to the grammatical structure being unaware of the odd lexical meaning. Most of the results of total aphasics were similar to those of Wernicke's aphasics others however performed like Broca's aphasics.", "contents": "Some relations of grammar and lexicon in aphasia. A new form of a Sentence Order Test was applied to a group of Broca's, Wernicke's and total aphasics. Sentences cut into three movable cards should be put together. Some of the sentences could be arranged in two different ways. Broca's aphasics prefered to order the parts according to a logical string of lexical items neglecting the grammatical errors. Wernicke's aphasics arranged the material according to the grammatical structure being unaware of the odd lexical meaning. Most of the results of total aphasics were similar to those of Wernicke's aphasics others however performed like Broca's aphasics."} {"id": "PMID:1261284", "title": "Paired associate learning of Morse code and Braille letter names by dyslexic and normal children.", "content": "Twenty dyslexic and twenty normal children, matched for age and sex and with the same mean I.Q. were tested on their ability to learn letter names of Braille configurations presented visually or tactually and to Morse Code signals presented aurally. The dyslexic Ss learned fewer letters in all three modalities although for both groups the visual-verbal method was easiest. The deficits were not attributable to specific modality dysfunction nor to a failure of intersensory integration. More general encoding and retrieval difficulties appear to be implicated.", "contents": "Paired associate learning of Morse code and Braille letter names by dyslexic and normal children. Twenty dyslexic and twenty normal children, matched for age and sex and with the same mean I.Q. were tested on their ability to learn letter names of Braille configurations presented visually or tactually and to Morse Code signals presented aurally. The dyslexic Ss learned fewer letters in all three modalities although for both groups the visual-verbal method was easiest. The deficits were not attributable to specific modality dysfunction nor to a failure of intersensory integration. More general encoding and retrieval difficulties appear to be implicated."} {"id": "PMID:1261285", "title": "Hemispheric specialization for speech perception in four-year-old children from low and middle socio-economic classes.", "content": "Four-year-old male and female children from low and middle socio-economic class (SEC) were presented a dichotic syllable task. Both low and middle SEC males evidenced significant right-ear advantages. Neither low nor middle SEC females evidenced a significant right-ear advantage. The similar ear advantage in the low and middle SEC populations replicates a previous study with six-year-olds and suggests that the variations in rearing conditions which occur in low and middle SEC classes does not affect hemispheric lateralization for speech perception.", "contents": "Hemispheric specialization for speech perception in four-year-old children from low and middle socio-economic classes. Four-year-old male and female children from low and middle socio-economic class (SEC) were presented a dichotic syllable task. Both low and middle SEC males evidenced significant right-ear advantages. Neither low nor middle SEC females evidenced a significant right-ear advantage. The similar ear advantage in the low and middle SEC populations replicates a previous study with six-year-olds and suggests that the variations in rearing conditions which occur in low and middle SEC classes does not affect hemispheric lateralization for speech perception."} {"id": "PMID:1261299", "title": "Toxicological studies on azapropazone.", "content": "The toxicity of azapropazone, a non-steroidal anti-inflammatory analgesic compound was studied in mice, rats, hamsters, guinea pigs, rabbits, cats, mongrel and beagle dogs, domestic pigs, rhesus monkeys, cynomolgus monkeys and baboons in experiments which ranged from acute, single-dose studies up to treatment periods of 1 year. The beagle dog was found to be especially sensitive to gastro-intestinal ulceration from azapropazone and this contrasted with the marked lack of gastro-intestinal hazard to other animals and particularly to the 3 primate species studied. The animal experiments did not indicate any potential risk to other body systems, and comparisons with other anti-inflammatory compounds, where these were made, suggest that azapropazone is at least as safe as other commonly-used agents. Azapropazone was not found to have teratogenic, carcinogenic or antimitotic activity and was shown not to produce local tissue damage.", "contents": "Toxicological studies on azapropazone. The toxicity of azapropazone, a non-steroidal anti-inflammatory analgesic compound was studied in mice, rats, hamsters, guinea pigs, rabbits, cats, mongrel and beagle dogs, domestic pigs, rhesus monkeys, cynomolgus monkeys and baboons in experiments which ranged from acute, single-dose studies up to treatment periods of 1 year. The beagle dog was found to be especially sensitive to gastro-intestinal ulceration from azapropazone and this contrasted with the marked lack of gastro-intestinal hazard to other animals and particularly to the 3 primate species studied. The animal experiments did not indicate any potential risk to other body systems, and comparisons with other anti-inflammatory compounds, where these were made, suggest that azapropazone is at least as safe as other commonly-used agents. Azapropazone was not found to have teratogenic, carcinogenic or antimitotic activity and was shown not to produce local tissue damage."} {"id": "PMID:1261300", "title": "The determination of azapropazone in blood plasma.", "content": "Three methods for the determination of azapropazone were studied for the analysis of blood plasma samples taken after oral administration of azapropazone. A gas chromatographic method was compared with two simple spectrophotometric assay methods and the effect of metabolites of the drug on each method is described. It is concluded that metabolites are unlikely to cause significant interference with the two simple methods and that either is suitable for determination of plasma levels of the drug. Some problems associated with a gas chromatographic method are described and the comparative results of the examination of plasma samples using these methods are given.", "contents": "The determination of azapropazone in blood plasma. Three methods for the determination of azapropazone were studied for the analysis of blood plasma samples taken after oral administration of azapropazone. A gas chromatographic method was compared with two simple spectrophotometric assay methods and the effect of metabolites of the drug on each method is described. It is concluded that metabolites are unlikely to cause significant interference with the two simple methods and that either is suitable for determination of plasma levels of the drug. Some problems associated with a gas chromatographic method are described and the comparative results of the examination of plasma samples using these methods are given."} {"id": "PMID:1261301", "title": "Long-term use of azapropazone in rheumatoid conditions.", "content": "In an open assessment of azapropazone, 51 patients with rheumatoid disorders, mainly rheumatoid arthritis, were treated continuously for periods up to 3 years (range 2 weeks to 38 months). Treatment was interrupted or discontinued in 9 patients for various reasons. Initial dosage was 1200 mg. daily, but this was usually reduced after a few months to a maintenance level of 900 mg. daily. An overall assessment of patient response at the end of the study period indicated that only 4 (7.8%) of the 51 patients failed to obtain satisfactory relief during treatment: 28 (54.6%) showed objective signs of improvement, such as reduced joint swelling and stiffness, as well as subjective evidence of symptom relief, and a further 19 patients (37.3%) reported an equivocal analgesic effect with azapropazone. Few side-effects were reported, mainly mild gastralgia and nausea, and routine laboratory investigations throughout the long-term study revealed no abnormalities in the blood picture, liver or renal function or coagulation factors. There was also no evidence of any interaction between azapropazone and other drugs used concomitantly.", "contents": "Long-term use of azapropazone in rheumatoid conditions. In an open assessment of azapropazone, 51 patients with rheumatoid disorders, mainly rheumatoid arthritis, were treated continuously for periods up to 3 years (range 2 weeks to 38 months). Treatment was interrupted or discontinued in 9 patients for various reasons. Initial dosage was 1200 mg. daily, but this was usually reduced after a few months to a maintenance level of 900 mg. daily. An overall assessment of patient response at the end of the study period indicated that only 4 (7.8%) of the 51 patients failed to obtain satisfactory relief during treatment: 28 (54.6%) showed objective signs of improvement, such as reduced joint swelling and stiffness, as well as subjective evidence of symptom relief, and a further 19 patients (37.3%) reported an equivocal analgesic effect with azapropazone. Few side-effects were reported, mainly mild gastralgia and nausea, and routine laboratory investigations throughout the long-term study revealed no abnormalities in the blood picture, liver or renal function or coagulation factors. There was also no evidence of any interaction between azapropazone and other drugs used concomitantly."} {"id": "PMID:1261302", "title": "Life style and nutrient intake in the elderly.", "content": "The life styles of the elderly population under study indicate that they had positive attitudes toward health in general and toward food and eating, Their food habits and beliefs were free from faddism, they were willing to try new foods and to change at least some of their food habits, and they had a good appetite for meals. Meal patterns and choice of foods, snacks, and food likes were toward foods of high nutritive value. They had comparatively few food dislikes, and the majority ate three meals a day. Many of the participants in this study had nutrient intakes of less than two-thirds the 1974 RDA'S. Food choices, meal patterns, and beliefs about food suggest that economic factors strongly influenced dietary adequacy and limited the food choices and size of servings. Black females appear to be the most disadvantaged group. All of these findings are a strong indicator of the need for group feeding programs for the elderly. Such meal programs should provide at least one-third of the daily nutrient needs, and should be pleasurable experiences using foods appropriate to the food habits and beliefs of the specific groups, their locale, and their cultural-economic backgrounds. These programs should also be accompanied by realistic nutrition education programs designed to provide guidance in buying and using foods of highest nutritive value within their resources. The need for such programs becomes increasingly urgent because of today's rapidly increasing food prices.", "contents": "Life style and nutrient intake in the elderly. The life styles of the elderly population under study indicate that they had positive attitudes toward health in general and toward food and eating, Their food habits and beliefs were free from faddism, they were willing to try new foods and to change at least some of their food habits, and they had a good appetite for meals. Meal patterns and choice of foods, snacks, and food likes were toward foods of high nutritive value. They had comparatively few food dislikes, and the majority ate three meals a day. Many of the participants in this study had nutrient intakes of less than two-thirds the 1974 RDA'S. Food choices, meal patterns, and beliefs about food suggest that economic factors strongly influenced dietary adequacy and limited the food choices and size of servings. Black females appear to be the most disadvantaged group. All of these findings are a strong indicator of the need for group feeding programs for the elderly. Such meal programs should provide at least one-third of the daily nutrient needs, and should be pleasurable experiences using foods appropriate to the food habits and beliefs of the specific groups, their locale, and their cultural-economic backgrounds. These programs should also be accompanied by realistic nutrition education programs designed to provide guidance in buying and using foods of highest nutritive value within their resources. The need for such programs becomes increasingly urgent because of today's rapidly increasing food prices."} {"id": "PMID:1261307", "title": "Avoiding malpractice suits through the use of informed consent.", "content": "The doctrine of informed consent is based on a long tradition of promoting self-autonomy and rational decision-making. The amount of information required to be disclosed by the doctor to the patient is that which permits the patient to decide for himself whether or not to undergo the recommended treatment. It includes information about risks of death or serious bodily harm, probability of success, problems of recuperation, and alternative modes of treatment. Disclosing such information contributes to the doctor-patient relationship and therefore makes recourse to malpractice litigation in the face of an unsatisfactory or untoward result less likely. Attempts to abolish the doctrine are potentially counterproductive and could lead to widespread mistrust of the medical profession on the part of a society that increasingly demands more information in all areas. Physicians will best serve both themselves and their patients by fully disclosing all relevant information before asking patients to consent to specific therapies.", "contents": "Avoiding malpractice suits through the use of informed consent. The doctrine of informed consent is based on a long tradition of promoting self-autonomy and rational decision-making. The amount of information required to be disclosed by the doctor to the patient is that which permits the patient to decide for himself whether or not to undergo the recommended treatment. It includes information about risks of death or serious bodily harm, probability of success, problems of recuperation, and alternative modes of treatment. Disclosing such information contributes to the doctor-patient relationship and therefore makes recourse to malpractice litigation in the face of an unsatisfactory or untoward result less likely. Attempts to abolish the doctrine are potentially counterproductive and could lead to widespread mistrust of the medical profession on the part of a society that increasingly demands more information in all areas. Physicians will best serve both themselves and their patients by fully disclosing all relevant information before asking patients to consent to specific therapies."} {"id": "PMID:1261311", "title": "Clinical comparison of two electronic spirometers with a water-sealed spirometer.", "content": "Two electronic spirometers which use a hot-wire anemometer to measure air flow were clinically compared with a water-sealed spirometer. The forced vital capacity (FVC), the forced expiratory volume in one second (FEV1), the FEV1/FVC%, the mean forced expiratory flow between 200 and 1,200 ml of the FVC, the mean forced expiratory flow during the middle half of the FVC, the mean forced expiratory flow between 75 and 85 percent of the FVC, and the maximum voluntary ventilation were determined for a group of 67 subjects. Techniques are described for connecting the spirometers in series to permit evaluation by human subjects or by syringe injection. High correlation coefficients generally were obtained when comparing the electronic spirometers with the water-sealed spirometer, but the actual range of percent difference was greater than 11 percent in all spirometric tests. The results indicate the need for systematic evaluation of electronic spirometers to characterize their deviation from accented standards. Frequent calibration is necessary to maintain consistent performance.", "contents": "Clinical comparison of two electronic spirometers with a water-sealed spirometer. Two electronic spirometers which use a hot-wire anemometer to measure air flow were clinically compared with a water-sealed spirometer. The forced vital capacity (FVC), the forced expiratory volume in one second (FEV1), the FEV1/FVC%, the mean forced expiratory flow between 200 and 1,200 ml of the FVC, the mean forced expiratory flow during the middle half of the FVC, the mean forced expiratory flow between 75 and 85 percent of the FVC, and the maximum voluntary ventilation were determined for a group of 67 subjects. Techniques are described for connecting the spirometers in series to permit evaluation by human subjects or by syringe injection. High correlation coefficients generally were obtained when comparing the electronic spirometers with the water-sealed spirometer, but the actual range of percent difference was greater than 11 percent in all spirometric tests. The results indicate the need for systematic evaluation of electronic spirometers to characterize their deviation from accented standards. Frequent calibration is necessary to maintain consistent performance."} {"id": "PMID:1261312", "title": "Painless ST-segment depression in patients with angina pectoris. Correlation with daily activities and cigarette smoking.", "content": "Ambulatory electrocardiographic monitoring was employed in 33 patients with angina pectoris and abnormal stress tests to determine the frequency with which myocardial ischemia manifested by painless ST-segment depression occurred during normal activity. ST-segment depression occurred in 24 patients during the monitoring period; and in 21, it occurred either solely in the absence of pain or both with and without pain. Of 109 recorded episodes of ST-segment depression, 61 percent were painless. The frequency of painless ST-segment depression was independent of activity other than automobile driving, during which all episodes were painless. In patients who smoked cigarettes, ST-segment depression was more common while smoking, but the incidence of painless ST-segment depression was not altered. The study indicates that ST-segment depression occurs more commonly in the absence than in the presence of chest pain and that ambulatory electrocardiographic monitoring is a useful method of determining the frequency of myocardial ischemia during normal daily activity.", "contents": "Painless ST-segment depression in patients with angina pectoris. Correlation with daily activities and cigarette smoking. Ambulatory electrocardiographic monitoring was employed in 33 patients with angina pectoris and abnormal stress tests to determine the frequency with which myocardial ischemia manifested by painless ST-segment depression occurred during normal activity. ST-segment depression occurred in 24 patients during the monitoring period; and in 21, it occurred either solely in the absence of pain or both with and without pain. Of 109 recorded episodes of ST-segment depression, 61 percent were painless. The frequency of painless ST-segment depression was independent of activity other than automobile driving, during which all episodes were painless. In patients who smoked cigarettes, ST-segment depression was more common while smoking, but the incidence of painless ST-segment depression was not altered. The study indicates that ST-segment depression occurs more commonly in the absence than in the presence of chest pain and that ambulatory electrocardiographic monitoring is a useful method of determining the frequency of myocardial ischemia during normal daily activity."} {"id": "PMID:1261313", "title": "Development of \"resistance\" in beta-adrenergic receptors of asthmatic patients.", "content": "Complete in vitro dose-response curves for (see article) -isoproterenol (isoprenaline) sulfate showed no functional defects in bronchial muscular beta-adrenergic receptors in three patients with chronic intrinsic asthma, as compared to 60 patients with normal pulmonary function. Complete in vivo dose-response curves for intravenously infused isoproterenol were obtained in eight outpatients with chronic intrinsic asthma to register effects on bronchial muscle (forced expiratory volume in one second), heart rate, blood pressure, and skeletal muscular tremor. The isoproterenol test was performed before and also during oral treatment with a long-acting selective beta-adrenergic stimulator (terbutaline sulfate, 5 mg three times daily). The study was performed over 12 months to avoid seasonal variation in basal levels of obstruction and was concluded by adding inhaled terbutaline (two inhalations four times daily) to oral therapy. No \"resistance\" developed in bronchial beta-adrenergic receptors during this prolonged treatment. Inhalation therapy in addition to oral therapy improved bronchodilation without causing resistance. Even six inhalations given four times daily (four- to five-hour intervals) did not cause any bronchial resistance; however, resistance developed in skeletal muscles with decreased tremor and in cardiac beta-adrenergic receptors.", "contents": "Development of \"resistance\" in beta-adrenergic receptors of asthmatic patients. Complete in vitro dose-response curves for (see article) -isoproterenol (isoprenaline) sulfate showed no functional defects in bronchial muscular beta-adrenergic receptors in three patients with chronic intrinsic asthma, as compared to 60 patients with normal pulmonary function. Complete in vivo dose-response curves for intravenously infused isoproterenol were obtained in eight outpatients with chronic intrinsic asthma to register effects on bronchial muscle (forced expiratory volume in one second), heart rate, blood pressure, and skeletal muscular tremor. The isoproterenol test was performed before and also during oral treatment with a long-acting selective beta-adrenergic stimulator (terbutaline sulfate, 5 mg three times daily). The study was performed over 12 months to avoid seasonal variation in basal levels of obstruction and was concluded by adding inhaled terbutaline (two inhalations four times daily) to oral therapy. No \"resistance\" developed in bronchial beta-adrenergic receptors during this prolonged treatment. Inhalation therapy in addition to oral therapy improved bronchodilation without causing resistance. Even six inhalations given four times daily (four- to five-hour intervals) did not cause any bronchial resistance; however, resistance developed in skeletal muscles with decreased tremor and in cardiac beta-adrenergic receptors."} {"id": "PMID:1261314", "title": "Effect of exercise on left ventricular ejection time in patients with prolapsing mitral leaflet syndrome.", "content": "The effect of exercise on left ventricular ejection time was determined in 12 subjects with prolapsing mitral valve leaflet syndrome (PML). A single lead ECG (CM5), phonocardiogram and carotid pulse contour were recorded simultaneously with the subjects at supine rest before and immediately after multistage treadmill exercise. Systolic time intervals were measured from five consecutive complexes to determine the pre-ejection period (PEP), left ventricular ejection time (LVET) and total electromechanical systole (QS2). LVET was corrected for heart rate and defines as LVETc. In nine subjects, an increase of 1 to 49 msec was observed in the LVETc following exercise. A shorter resting LVETc and greater afterload at peak exercise was related to an increase in LVETc of 10 msec or more. Exercise elicited or evoked evidence of left ventricular dysfunction. The results support the concept that impaired left ventricular performance is a concomitant of this syndrome.", "contents": "Effect of exercise on left ventricular ejection time in patients with prolapsing mitral leaflet syndrome. The effect of exercise on left ventricular ejection time was determined in 12 subjects with prolapsing mitral valve leaflet syndrome (PML). A single lead ECG (CM5), phonocardiogram and carotid pulse contour were recorded simultaneously with the subjects at supine rest before and immediately after multistage treadmill exercise. Systolic time intervals were measured from five consecutive complexes to determine the pre-ejection period (PEP), left ventricular ejection time (LVET) and total electromechanical systole (QS2). LVET was corrected for heart rate and defines as LVETc. In nine subjects, an increase of 1 to 49 msec was observed in the LVETc following exercise. A shorter resting LVETc and greater afterload at peak exercise was related to an increase in LVETc of 10 msec or more. Exercise elicited or evoked evidence of left ventricular dysfunction. The results support the concept that impaired left ventricular performance is a concomitant of this syndrome."} {"id": "PMID:1261315", "title": "Pacemaker-induced change in prosthetic valvular sounds.", "content": "Variable intensity and timing of valvular sounds were noted in two patients with permanent pacemakers and prosthetic valves. In the first patient, who had a mitral and a tricuspid prosthesis, valvular opening sounds became widely separated with a change from nodal to ventricular paced rhythm. In a second patient, who had a mitral prosthesis in sinus rhythm with first-degree atrioventricular block, a very quiet closing sound increased markedly in intensity with the onset of ventricular pacing. The mechanism for these changes is described using a technique which at brief intervals throughout the cardiac cycle permitted documentation of simultaneously recorded phonocardiogram, electrocardiogram, and pulse tracings with a visible image of the prosthesis. In the usual patient with a prosthetic valve auscultatory changes should arouse a suspicion of malfunction; however, in the relatively uncommon patient with a prosthesis and an artificial pacemaker, it should be recognized that auscultatory changes may well have a physiologic explanation.", "contents": "Pacemaker-induced change in prosthetic valvular sounds. Variable intensity and timing of valvular sounds were noted in two patients with permanent pacemakers and prosthetic valves. In the first patient, who had a mitral and a tricuspid prosthesis, valvular opening sounds became widely separated with a change from nodal to ventricular paced rhythm. In a second patient, who had a mitral prosthesis in sinus rhythm with first-degree atrioventricular block, a very quiet closing sound increased markedly in intensity with the onset of ventricular pacing. The mechanism for these changes is described using a technique which at brief intervals throughout the cardiac cycle permitted documentation of simultaneously recorded phonocardiogram, electrocardiogram, and pulse tracings with a visible image of the prosthesis. In the usual patient with a prosthetic valve auscultatory changes should arouse a suspicion of malfunction; however, in the relatively uncommon patient with a prosthesis and an artificial pacemaker, it should be recognized that auscultatory changes may well have a physiologic explanation."} {"id": "PMID:1261316", "title": "Focal myocytolysis mimicking the electrocardiographic pattern of transmural anteroseptal myocardial infarction.", "content": "Two patients are documented, one with a cerebral infarct and one with a primary brain tumor, both of whom initially had a normal electrocardiogram but subsequently developed the classic pattern of transmural anteroseptal myocardial infarction; however, in both cases the autopsy proved the electrocardiograph pattern to be related to \"focal myocytolysis\" of the myocardium. Both patients also exhibited coronary arterial disease of the localized type and to a maximal luminal narrowing of 75 percent without a history of anginal complaints. It is of interest that the intensity of the lesions of focal myocytolysis was greatest in the areas supplied by the affected arteries. This peculiarity suggests that ischemia, though not primarily involved in inducing the lesions, could be of additional significance.", "contents": "Focal myocytolysis mimicking the electrocardiographic pattern of transmural anteroseptal myocardial infarction. Two patients are documented, one with a cerebral infarct and one with a primary brain tumor, both of whom initially had a normal electrocardiogram but subsequently developed the classic pattern of transmural anteroseptal myocardial infarction; however, in both cases the autopsy proved the electrocardiograph pattern to be related to \"focal myocytolysis\" of the myocardium. Both patients also exhibited coronary arterial disease of the localized type and to a maximal luminal narrowing of 75 percent without a history of anginal complaints. It is of interest that the intensity of the lesions of focal myocytolysis was greatest in the areas supplied by the affected arteries. This peculiarity suggests that ischemia, though not primarily involved in inducing the lesions, could be of additional significance."} {"id": "PMID:1261317", "title": "Pulmonary fibrosis associated with tracheobronchial aspiration. A study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology.", "content": "Tracheobronchial aspiration of gastric secretions has been suggested in published reports as a possible cause for idiopathic pulmonary fibrosis. Forty-eight of 131 patients with roentgenographic evidence of pulmonary fibrosis had no established etiologic diagnosis after individualized evaluations. They were prospectively studied by upper gastrointestinal series to determine the incidence of gastroesophageal reflux. The incidence of both hiatal hernia and reflux were statistically higher in the study group than in a group of 270 age-matched controls who had upper gastrointestinal series for the usual indications; (2) a subgroup of 15 patients who had pulmonary fibrosis and serologic evidence which suggested immune-mediated diseases; and (3) a subgroup of 23 patients with pulmonary fibrosis of established etiology. The patients in the study group could be further characterized by clinical and roentgenographic presentations, low maximum-mid-expiratory flow rates, and lung biopsies compatible with interstitial fibrosis. These observations and other cited evidence are supportive of the concept that repeated, small tracheobronchial aspirations of gastric acid secretions over a long period of time may cause interstitial pulmonary fibrosis.", "contents": "Pulmonary fibrosis associated with tracheobronchial aspiration. A study of the frequency of hiatal hernia and gastroesophageal reflux in interstitial pulmonary fibrosis of obscure etiology. Tracheobronchial aspiration of gastric secretions has been suggested in published reports as a possible cause for idiopathic pulmonary fibrosis. Forty-eight of 131 patients with roentgenographic evidence of pulmonary fibrosis had no established etiologic diagnosis after individualized evaluations. They were prospectively studied by upper gastrointestinal series to determine the incidence of gastroesophageal reflux. The incidence of both hiatal hernia and reflux were statistically higher in the study group than in a group of 270 age-matched controls who had upper gastrointestinal series for the usual indications; (2) a subgroup of 15 patients who had pulmonary fibrosis and serologic evidence which suggested immune-mediated diseases; and (3) a subgroup of 23 patients with pulmonary fibrosis of established etiology. The patients in the study group could be further characterized by clinical and roentgenographic presentations, low maximum-mid-expiratory flow rates, and lung biopsies compatible with interstitial fibrosis. These observations and other cited evidence are supportive of the concept that repeated, small tracheobronchial aspirations of gastric acid secretions over a long period of time may cause interstitial pulmonary fibrosis."} {"id": "PMID:1261318", "title": "Xerotomography of peripheral lung lesions.", "content": "Xerotomography was compared to conventional tomography in 72 patients with peripheral lung lesions. The xerotomogram was superior to the conventional tomogram in 41 patients, and yielded no additional information in 31. Details of lesions were better displayed, especially the margins: cavitations, air bronchogram and bronchiectasis, and calcification. Differentiation between benign, inflammatory and malignant lesions was facilitated. The xerotomographic process improved the image detail of lesions due to the edge enhancement property and the greater recording latitude of contrast of the xeroradiographs. Xerotomography is recommended only in selected patients for a few tomographic cuts because of the high radiation dosage.", "contents": "Xerotomography of peripheral lung lesions. Xerotomography was compared to conventional tomography in 72 patients with peripheral lung lesions. The xerotomogram was superior to the conventional tomogram in 41 patients, and yielded no additional information in 31. Details of lesions were better displayed, especially the margins: cavitations, air bronchogram and bronchiectasis, and calcification. Differentiation between benign, inflammatory and malignant lesions was facilitated. The xerotomographic process improved the image detail of lesions due to the edge enhancement property and the greater recording latitude of contrast of the xeroradiographs. Xerotomography is recommended only in selected patients for a few tomographic cuts because of the high radiation dosage."} {"id": "PMID:1261319", "title": "Left axis deviation: diagnostic contribution of stress testing and post-exercise systolic time intervals.", "content": "The response to graded submaximal upright bicycle ergometry combined with resting and postexercise systolic time intervals (STIs) was investigated in ten ambulatory subjects (study group) with normal electrocardiograms except for a frontal plane axis of greater than or equal to -30 degrees, or left axis deviation (LAD) mean -40 degrees); and eight age-matched volunteers (control group) with a normal ECG and frontal plane axis (mean +35 degrees). Following a 12-lead resting ECG, supine STIs were measured. The subjects then exercised on a bicycle ergometer at progressive workloads with ECG and blood pressure monitoring until a heart rate based on 85 percent of tha age-predicted maximum was attained or an abnormal end point was noted. STIs were repeated immediately postexercise. Prolongation of left ventricular ejection time corrected for heart rate (LVETc) of 8 msecs or more from rest to post-exercise. (deltaLVETc) was considered an abnormal STI response. The deltaLVETc can elicit left ventricular dysfunction and possible latent organic heart disease in patients with isolated left axis deviation.", "contents": "Left axis deviation: diagnostic contribution of stress testing and post-exercise systolic time intervals. The response to graded submaximal upright bicycle ergometry combined with resting and postexercise systolic time intervals (STIs) was investigated in ten ambulatory subjects (study group) with normal electrocardiograms except for a frontal plane axis of greater than or equal to -30 degrees, or left axis deviation (LAD) mean -40 degrees); and eight age-matched volunteers (control group) with a normal ECG and frontal plane axis (mean +35 degrees). Following a 12-lead resting ECG, supine STIs were measured. The subjects then exercised on a bicycle ergometer at progressive workloads with ECG and blood pressure monitoring until a heart rate based on 85 percent of tha age-predicted maximum was attained or an abnormal end point was noted. STIs were repeated immediately postexercise. Prolongation of left ventricular ejection time corrected for heart rate (LVETc) of 8 msecs or more from rest to post-exercise. (deltaLVETc) was considered an abnormal STI response. The deltaLVETc can elicit left ventricular dysfunction and possible latent organic heart disease in patients with isolated left axis deviation."} {"id": "PMID:1261320", "title": "The role of hypovolemic stress in the production of fat embolism in rabbits. 1. Morphologic alterations of the lungs.", "content": "In rabbits, an experimental model of fat embolism was produced that simulates the course of events in the clinical situation. Small doses of fat-cell suspension (0.075 ml/kg of body weight), prepared by collagenase treatment of homologous adipose tissue, were injected intravenously. Concomitantly, hypovolemia was produced in two animal groups by either withdrawing 20 percent of the estimated blood volume or by application of a hind-limb ischemic tourniquet for 90 minutes. The presence of pathoanatomic characteristics typical of fat embolism was evaluated by recording lung/body weights, macroscopic appearance, and semiquantitative microscopic estimation in the lungs of edema, hemorrhage, atelectasis, intravascular coagulation, and leukocytic thrombi. Mean indices of lung/body weight were higher in all animals receiving injections of fat-cell suspension, as compared to controls. The score for microscopic generalized pulmonary damage was significantly higher in rabbits exposed to both fat-cell injections and hypovolemia than in controls or after fat-cell injections alone. It is concluded that hypovolemia enhances the development of fat embolism in rabbits subjected to small doses of fat-cell suspension.", "contents": "The role of hypovolemic stress in the production of fat embolism in rabbits. 1. Morphologic alterations of the lungs. In rabbits, an experimental model of fat embolism was produced that simulates the course of events in the clinical situation. Small doses of fat-cell suspension (0.075 ml/kg of body weight), prepared by collagenase treatment of homologous adipose tissue, were injected intravenously. Concomitantly, hypovolemia was produced in two animal groups by either withdrawing 20 percent of the estimated blood volume or by application of a hind-limb ischemic tourniquet for 90 minutes. The presence of pathoanatomic characteristics typical of fat embolism was evaluated by recording lung/body weights, macroscopic appearance, and semiquantitative microscopic estimation in the lungs of edema, hemorrhage, atelectasis, intravascular coagulation, and leukocytic thrombi. Mean indices of lung/body weight were higher in all animals receiving injections of fat-cell suspension, as compared to controls. The score for microscopic generalized pulmonary damage was significantly higher in rabbits exposed to both fat-cell injections and hypovolemia than in controls or after fat-cell injections alone. It is concluded that hypovolemia enhances the development of fat embolism in rabbits subjected to small doses of fat-cell suspension."} {"id": "PMID:1261324", "title": "Lung abscess and osteomyelitis of rib due to Yersinia enterocolitica.", "content": "The first reported case of infection of the lung and bone with Yersinia enterocolitica is described. This organism has only recently been known to infect humans. Although a wide spectrum of diseases has been described, all have appeared to be relatively benign; however, in our case a rapid necrotizing process occurred. Therefore, the aggressive nature of this organism outside its usual surroundings, eg, the gastrointestinal tract, is worth noting.", "contents": "Lung abscess and osteomyelitis of rib due to Yersinia enterocolitica. The first reported case of infection of the lung and bone with Yersinia enterocolitica is described. This organism has only recently been known to infect humans. Although a wide spectrum of diseases has been described, all have appeared to be relatively benign; however, in our case a rapid necrotizing process occurred. Therefore, the aggressive nature of this organism outside its usual surroundings, eg, the gastrointestinal tract, is worth noting."} {"id": "PMID:1261325", "title": "Ectopic origin of the left anterior descending coronary artery from the right coronary sinus. Report of a case simulating anterior descending obstruction.", "content": "A patient with anomalous aortic origin of the left anterior descending coronary artery was studied. The clinical picture and the preliminary angiographic findings simulated obstruction of the left anterior descending coronary artery near its origin. Careful catheter exploration of the right coronary sinus led to the correct diagnosis, emphasizing the importance of complete visualization of all branches of the coronary tree, including distal radicles of a supposedly occluded vessel.", "contents": "Ectopic origin of the left anterior descending coronary artery from the right coronary sinus. Report of a case simulating anterior descending obstruction. A patient with anomalous aortic origin of the left anterior descending coronary artery was studied. The clinical picture and the preliminary angiographic findings simulated obstruction of the left anterior descending coronary artery near its origin. Careful catheter exploration of the right coronary sinus led to the correct diagnosis, emphasizing the importance of complete visualization of all branches of the coronary tree, including distal radicles of a supposedly occluded vessel."} {"id": "PMID:1261326", "title": "Congenital levojuxtaposition of the right atrial appendage. Association with persistent truncus arteriosus, type 4.", "content": "Congenital levojuxtaposition of the right atrial appendage is a rare malformation most commonly associated with a transposition of the great arteries. We report a case of levojuxtaposition of the right atrial appendage associated with a persistant truncus arteriosus, type 4. Juxtaposition of the atrial appendage is a sign of severe cyanotic congenital heart disease, and this is best diagnosed by a selective right atriogram or superior venacavogram.", "contents": "Congenital levojuxtaposition of the right atrial appendage. Association with persistent truncus arteriosus, type 4. Congenital levojuxtaposition of the right atrial appendage is a rare malformation most commonly associated with a transposition of the great arteries. We report a case of levojuxtaposition of the right atrial appendage associated with a persistant truncus arteriosus, type 4. Juxtaposition of the atrial appendage is a sign of severe cyanotic congenital heart disease, and this is best diagnosed by a selective right atriogram or superior venacavogram."} {"id": "PMID:1261327", "title": "Bronchiectasis following heroin-induced pulmonary edema. Rapid clearing of pulmonary infiltrates.", "content": "We observed a patient who developed diffuse bronchiectasis subsequent to heroin-induced pulmonary edema. Unlike the previously reported cases, there was rapid clearing of pulmonary infiltrates and little evidence of severe aspiration. The development of bronchiectasis was attributed to a bronchial infection subsequent to clearing of the pulmonary edema. Physiologic dysfunction was characterized by marked obstruction, pulmonary hypertension, and mild hypoxemia.", "contents": "Bronchiectasis following heroin-induced pulmonary edema. Rapid clearing of pulmonary infiltrates. We observed a patient who developed diffuse bronchiectasis subsequent to heroin-induced pulmonary edema. Unlike the previously reported cases, there was rapid clearing of pulmonary infiltrates and little evidence of severe aspiration. The development of bronchiectasis was attributed to a bronchial infection subsequent to clearing of the pulmonary edema. Physiologic dysfunction was characterized by marked obstruction, pulmonary hypertension, and mild hypoxemia."} {"id": "PMID:1261328", "title": "Monocular blindness secondary to calcific embolization. An unusual presentation of rheumatic mitral valvular disease.", "content": "This report of a patient with systemic calcific embolization resulting in nonocular blindness represents an unusual presentation and complication of mitral valvular disease.", "contents": "Monocular blindness secondary to calcific embolization. An unusual presentation of rheumatic mitral valvular disease. This report of a patient with systemic calcific embolization resulting in nonocular blindness represents an unusual presentation and complication of mitral valvular disease."} {"id": "PMID:1261329", "title": "Viral inclusion bodies in tracheobronchial epithelium of asymptomatic subjects.", "content": "During a survey conducted for the cytodiagnosis of early bronchogenic carcinoma, cytoplasmic viral inclusion bodies were found sporadically in tracheobronchial smears of asymtomatic patients of both sexes (ages ranging from 18 to 80 years) undergoing general endotracheal anesthesia for surgery. A review of 3,049 cases performed to assess the frequency of occurrence of this phenomenon showed a 1.1 percent incidence in all smears studied. There was no relationship between smoking habit, age, or sex and the presence of inclusion bodies; however, there was a marked seasonal incidence, with 60 percent of inclusion-bearing smears being found during the months of January through March.", "contents": "Viral inclusion bodies in tracheobronchial epithelium of asymptomatic subjects. During a survey conducted for the cytodiagnosis of early bronchogenic carcinoma, cytoplasmic viral inclusion bodies were found sporadically in tracheobronchial smears of asymtomatic patients of both sexes (ages ranging from 18 to 80 years) undergoing general endotracheal anesthesia for surgery. A review of 3,049 cases performed to assess the frequency of occurrence of this phenomenon showed a 1.1 percent incidence in all smears studied. There was no relationship between smoking habit, age, or sex and the presence of inclusion bodies; however, there was a marked seasonal incidence, with 60 percent of inclusion-bearing smears being found during the months of January through March."} {"id": "PMID:1261330", "title": "Sick sinus syndrome requiring permanent pacemaker implantation in a patient with mirror-image dextrocardia.", "content": "A patient with the sick sinus syndrome accompanying mirror-image dextrocardia which was associated with double superior venae cavae and an absent inferior vena cava is presented. A permanent transvenous demand pacemaker was inserted because of repeated episodes of dizziness and a documented 31/2-second period of asystole. Precise knowledge of the venous system and the location of the apex of the right ventricle was necessary prior to permanent pacemaker implantation.", "contents": "Sick sinus syndrome requiring permanent pacemaker implantation in a patient with mirror-image dextrocardia. A patient with the sick sinus syndrome accompanying mirror-image dextrocardia which was associated with double superior venae cavae and an absent inferior vena cava is presented. A permanent transvenous demand pacemaker was inserted because of repeated episodes of dizziness and a documented 31/2-second period of asystole. Precise knowledge of the venous system and the location of the apex of the right ventricle was necessary prior to permanent pacemaker implantation."} {"id": "PMID:1261331", "title": "Aspergilloma within a malignant pulmonary cavity.", "content": "The simultaneous appearance of both bronchogenic carcinoma and aspergilloma with the typical radiographic appearance of a mycetoma emphasizes the importance of consistent suspicion for malignancy in any pulmonary lesion. This is apparently the first reported case in which allergic phenomena (asthma-like symptoms and eosinophilia) are associated with an aspergilloma occurring within a cavitary bronchogenic carcinoma.", "contents": "Aspergilloma within a malignant pulmonary cavity. The simultaneous appearance of both bronchogenic carcinoma and aspergilloma with the typical radiographic appearance of a mycetoma emphasizes the importance of consistent suspicion for malignancy in any pulmonary lesion. This is apparently the first reported case in which allergic phenomena (asthma-like symptoms and eosinophilia) are associated with an aspergilloma occurring within a cavitary bronchogenic carcinoma."} {"id": "PMID:1261332", "title": "Application of systolic time intervals to acute cardiomyopathy with echovirous 2.", "content": "The occurrence of echovirus type 2 myocarditis in an adult is reported. Myocarditis was substantiated by abnormal electrocardiograms. More important, a prolonged course and severe functional impairment was quantitatively assessed by serial systolic time intervals, even after the ECGs became normal. The patient also had meningitis, hemiparesis, and convulsions. Viral isolation was from the spinal fluid.", "contents": "Application of systolic time intervals to acute cardiomyopathy with echovirous 2. The occurrence of echovirus type 2 myocarditis in an adult is reported. Myocarditis was substantiated by abnormal electrocardiograms. More important, a prolonged course and severe functional impairment was quantitatively assessed by serial systolic time intervals, even after the ECGs became normal. The patient also had meningitis, hemiparesis, and convulsions. Viral isolation was from the spinal fluid."} {"id": "PMID:1261333", "title": "Anomalous communication of the left coronary artery with a peripheral branch of the right pulmonary artery.", "content": "A 64-year old man had a history of two myocardial infarctions recurrent episodes of paroxysmal ventricular tachycardia and hemoptysis. Cineangiocardiographic studies showed an anomalous vessel connecting the left coronary artery with a peripheral branch of the right pulmonary artery. Although several coronary obstructive lesions and abnormalities in the distribution of the circumflex branches were found, the anomaly apparently produced a real \"pulmonary steal\" and, thereby a worsening of the coronary insufficiency. We believe that this is the first reported case in the literature with such a coronary-pulmonary fistula. The angiographic findings are presented in detail, and the possible factors in the development of myocardial ischemia are discussed.", "contents": "Anomalous communication of the left coronary artery with a peripheral branch of the right pulmonary artery. A 64-year old man had a history of two myocardial infarctions recurrent episodes of paroxysmal ventricular tachycardia and hemoptysis. Cineangiocardiographic studies showed an anomalous vessel connecting the left coronary artery with a peripheral branch of the right pulmonary artery. Although several coronary obstructive lesions and abnormalities in the distribution of the circumflex branches were found, the anomaly apparently produced a real \"pulmonary steal\" and, thereby a worsening of the coronary insufficiency. We believe that this is the first reported case in the literature with such a coronary-pulmonary fistula. The angiographic findings are presented in detail, and the possible factors in the development of myocardial ischemia are discussed."} {"id": "PMID:1261341", "title": "Is the centromeric heterochromatin of Mus musculus late replicating?", "content": "Quantitative analysis of DNA replication in embryonic cultures of C57BL/6J mice was carried out, using autoradiography after tritiated thymidine incorporation. The centromeric regions are late-replicating.", "contents": "Is the centromeric heterochromatin of Mus musculus late replicating? Quantitative analysis of DNA replication in embryonic cultures of C57BL/6J mice was carried out, using autoradiography after tritiated thymidine incorporation. The centromeric regions are late-replicating."} {"id": "PMID:1261343", "title": "Qualitative and quantitative EEG in psychotic children.", "content": "The EEGs of hospitalized psychotic boys were analyzed quantitatively by means of visual evaluation, analog frequency analysis, and digital computer period analysis and were compared with those of age- and sex-matched normals. Visual evaluation of the records demonstrated that psychotic children have significantly more beta activity as well as fewer alpha bursts than normal controls. EEG analog frequency analysis showed that psychotic children have a greater percentage of total voltage in the 3-5 cps and 13-33 cps bands, while they show less voltage in the 6-12 cps bands as compared with normal controls. Digital computer period analysis demonstrated more slow, less alpha, and more fast activity, as well as a greater average frequency and frequency deviation in both the primary wave and first derivative measurements in psychotic children than normals, while normals showed a trend towards higher amplitude and amplitude variability. The similarity of the EEG differences between psychotic and normal children to those differences observed between adult chronic schizophrenics and normals, as well as to those between children of \"high risk\" for becoming schizophrenic and controls, suggests that the above described findings are characteristic for the pathophysiology of schizophrenia.", "contents": "Qualitative and quantitative EEG in psychotic children. The EEGs of hospitalized psychotic boys were analyzed quantitatively by means of visual evaluation, analog frequency analysis, and digital computer period analysis and were compared with those of age- and sex-matched normals. Visual evaluation of the records demonstrated that psychotic children have significantly more beta activity as well as fewer alpha bursts than normal controls. EEG analog frequency analysis showed that psychotic children have a greater percentage of total voltage in the 3-5 cps and 13-33 cps bands, while they show less voltage in the 6-12 cps bands as compared with normal controls. Digital computer period analysis demonstrated more slow, less alpha, and more fast activity, as well as a greater average frequency and frequency deviation in both the primary wave and first derivative measurements in psychotic children than normals, while normals showed a trend towards higher amplitude and amplitude variability. The similarity of the EEG differences between psychotic and normal children to those differences observed between adult chronic schizophrenics and normals, as well as to those between children of \"high risk\" for becoming schizophrenic and controls, suggests that the above described findings are characteristic for the pathophysiology of schizophrenia."} {"id": "PMID:1261344", "title": "Epidemiology of tardive dyskinesia. Part II.", "content": "In the part II of an epidemiological study on tardive dyskinesia performed on the same sample of 332 chronic schizophrenic patients (142 males and 190 females), the authors come to the conclusion that the prevalence of tardive dyskinesia is significantly higher if the mean age was higher at the beginning of treatment with sedative or incisive neuroleptics, their combinations (cocktails) and added antiparkinsonian drugs. Age seems to be the most important factor in the prevalence of tardive dyskinesia. The mean longer duration of \"incisive\" free intervals significantly decreases the prevalence of tardive dyskinesia. Other factors analysed in our sample, especially the total amount of neuroleptics administered, the type of neuroleptics and the mean duration of neuroleptic treatment, do not play a significant role in the prevalence of tardive dyskinesia.", "contents": "Epidemiology of tardive dyskinesia. Part II. In the part II of an epidemiological study on tardive dyskinesia performed on the same sample of 332 chronic schizophrenic patients (142 males and 190 females), the authors come to the conclusion that the prevalence of tardive dyskinesia is significantly higher if the mean age was higher at the beginning of treatment with sedative or incisive neuroleptics, their combinations (cocktails) and added antiparkinsonian drugs. Age seems to be the most important factor in the prevalence of tardive dyskinesia. The mean longer duration of \"incisive\" free intervals significantly decreases the prevalence of tardive dyskinesia. Other factors analysed in our sample, especially the total amount of neuroleptics administered, the type of neuroleptics and the mean duration of neuroleptic treatment, do not play a significant role in the prevalence of tardive dyskinesia."} {"id": "PMID:1261346", "title": "Alcoholism, alcohol, intoxication and assaultive behavior.", "content": "The use of alcohol and the role of alcohol intoxication in the crime was studied in 307 males entering the North Carolina prison system after conviction of serious assaultive crimes. The majority (80%) were convicted of homicide (1st and 2nd degree murder and manslaughter), and the remainder (20%) committed a variety of felony assaults. Only 8% of the subjects were abstainers, and 36% were problem drinkers. The problem drinkers often had previous arrests for alcohol offenses (70%) and also were more likely to have previous nonalcohol criminal records (67%) and previous serious assaults (50%) than were other subjects. The problem drinkers were unlikely to have been engaged in treatment of alcoholism (13%) and almost never voluntarily sought treatment. The majority (58%) of the subjects were definitely drinking at the time of the crime, and a substantial number (40%) of the victims were definitely drinking at the time of the assault. Amnesia for the cime was uncommon (13%) among those who were drinking; but of those subjects who did claim amnesia, almost all had been drinking. Alcohol use appeared to be a significant ingredient in the production of the assaultive behavior in the majority of the cases. The majority of the subjects who were intoxicated at the time of the crime did not consider their state of intoxication as relevant to their behavior in spite of the seeming advantage to do so.", "contents": "Alcoholism, alcohol, intoxication and assaultive behavior. The use of alcohol and the role of alcohol intoxication in the crime was studied in 307 males entering the North Carolina prison system after conviction of serious assaultive crimes. The majority (80%) were convicted of homicide (1st and 2nd degree murder and manslaughter), and the remainder (20%) committed a variety of felony assaults. Only 8% of the subjects were abstainers, and 36% were problem drinkers. The problem drinkers often had previous arrests for alcohol offenses (70%) and also were more likely to have previous nonalcohol criminal records (67%) and previous serious assaults (50%) than were other subjects. The problem drinkers were unlikely to have been engaged in treatment of alcoholism (13%) and almost never voluntarily sought treatment. The majority (58%) of the subjects were definitely drinking at the time of the crime, and a substantial number (40%) of the victims were definitely drinking at the time of the assault. Amnesia for the cime was uncommon (13%) among those who were drinking; but of those subjects who did claim amnesia, almost all had been drinking. Alcohol use appeared to be a significant ingredient in the production of the assaultive behavior in the majority of the cases. The majority of the subjects who were intoxicated at the time of the crime did not consider their state of intoxication as relevant to their behavior in spite of the seeming advantage to do so."} {"id": "PMID:1261347", "title": "Psychiatric consultations in a general hospital. A report on 1,000 referrals.", "content": "1,000 medical and surgical inpatients referred for psychiatric conSULTATION SHOWED CONCURRENT PHYSICAL AND PSYCHIATRIC DISORDER IN 68.2% of cases. This is in accordance with epidemiological findings that these two types of morbidity have a positive association and coexist in 20-50% of patients. Depression was the commonest psychiatric disorder in all classes of organic disease and accounted for 53% of all psychiatric diagnoses. Organic brain syndromes, acute and chronic constituted 18% of referrals. Almost twice as many women as men were referred despite their nearly equal distribution in hospital population. One-third of the females had no positive medical diagnosis compared to one-fifth of the men. Alcoholism was a major problem in 8.9% of referrals. 7.8% of patients were referred following suicidal attempt. Of the 50 patients with cancer. 66% had depression. Too few medical patients with psychiatric complications are referred and adequately treated. Greater emphasis on teaching psychiatric syndromes is called for. Psychiatric consultation-liaison services offer the most direct form of collaboration between psychiatry and medicine in the interests of comprehensive patient care.", "contents": "Psychiatric consultations in a general hospital. A report on 1,000 referrals. 1,000 medical and surgical inpatients referred for psychiatric conSULTATION SHOWED CONCURRENT PHYSICAL AND PSYCHIATRIC DISORDER IN 68.2% of cases. This is in accordance with epidemiological findings that these two types of morbidity have a positive association and coexist in 20-50% of patients. Depression was the commonest psychiatric disorder in all classes of organic disease and accounted for 53% of all psychiatric diagnoses. Organic brain syndromes, acute and chronic constituted 18% of referrals. Almost twice as many women as men were referred despite their nearly equal distribution in hospital population. One-third of the females had no positive medical diagnosis compared to one-fifth of the men. Alcoholism was a major problem in 8.9% of referrals. 7.8% of patients were referred following suicidal attempt. Of the 50 patients with cancer. 66% had depression. Too few medical patients with psychiatric complications are referred and adequately treated. Greater emphasis on teaching psychiatric syndromes is called for. Psychiatric consultation-liaison services offer the most direct form of collaboration between psychiatry and medicine in the interests of comprehensive patient care."} {"id": "PMID:1261348", "title": "Psychiatric disorders and crime: a study of pretrial psychiatric examinations.", "content": "A study of 50 consecutive individuals referred for pretrial psychiatric examination, presumably because of previous psychiatric hospitalization (82 percent), indicated that antisocial personality, alcoholism, or drug dependence was present in 80 percent. Schizophrenia or bipolar affective disorder was seen in about a third of the subjects, usually associated as well, however, with antisocial personality, alcoholism, or drug dependence. There were no significant differences in index crime between those with or without schizophenia bipolar affective disorder. It is concluded that the latter conditions occur in no more than two or three per cent of all felons.", "contents": "Psychiatric disorders and crime: a study of pretrial psychiatric examinations. A study of 50 consecutive individuals referred for pretrial psychiatric examination, presumably because of previous psychiatric hospitalization (82 percent), indicated that antisocial personality, alcoholism, or drug dependence was present in 80 percent. Schizophrenia or bipolar affective disorder was seen in about a third of the subjects, usually associated as well, however, with antisocial personality, alcoholism, or drug dependence. There were no significant differences in index crime between those with or without schizophenia bipolar affective disorder. It is concluded that the latter conditions occur in no more than two or three per cent of all felons."} {"id": "PMID:1261361", "title": "[Treatment, follow-up and prognosis of drug addiction (author's transl)].", "content": "Using a standardised psychological questionnaire (self-estimation scale, personality-inventory FPI of Fahrenberg and Selg) and serial examinations, the effectiveness of a therapeutic concept combining drug, environmental and group therapy was tested. The psychological parameters objectified stabilisation of the psychological-autonomic and emotional areas as well as ego functions. The follow-up study extended over an average of five years and included 101 former drug addicts (14 could not be interviewed, 10 had died). Social stability was observed in 63% (satisfactory working performance, reduction of sexual problems, contacts with friends). 36% of the group had abstained from further drug taking, 27% were taking them periodically, 32% had to be treated again and 5% had deteriorated (trend towards invalidism).", "contents": "[Treatment, follow-up and prognosis of drug addiction (author's transl)]. Using a standardised psychological questionnaire (self-estimation scale, personality-inventory FPI of Fahrenberg and Selg) and serial examinations, the effectiveness of a therapeutic concept combining drug, environmental and group therapy was tested. The psychological parameters objectified stabilisation of the psychological-autonomic and emotional areas as well as ego functions. The follow-up study extended over an average of five years and included 101 former drug addicts (14 could not be interviewed, 10 had died). Social stability was observed in 63% (satisfactory working performance, reduction of sexual problems, contacts with friends). 36% of the group had abstained from further drug taking, 27% were taking them periodically, 32% had to be treated again and 5% had deteriorated (trend towards invalidism)."} {"id": "PMID:1261362", "title": "[Results of pacing after acute myocardial infarction (author's transl)].", "content": "Indications for electrical pacing were present in 58 of 665 patients with acute myocardial infarction (8.7%). Posterior-wall infarction had occurred in 34, anterior-wall infarction in 20, while two had combined infarction and in a further two precise localisation was not possible. There were 16 deaths (27.6%), six of them with posterior-wall and nine with anterior-wall infarction. Bradycardic arrhythmias with A-V block predominated among posterior-wall infarctions, hemiblocks and bifascicular block in anterior-wall infarctions. Permanent pacing was practised in 14 patients, 11 with posterior and three with anterior-wall infarctions, i.e. permanent pacing was four times as common after posterior than anterior-wall infarctions, the proportion being 2:1 for temporary pacing, largely due to a higher mortality-rate after anterior-wall infarction. Old anterior-wall scars were present in nine of eleven patients with permanent pacing. Because of the danger of late bradycardia or A-V block patients with posterior-wall infarction should be carefully followed in the late phase (from about the third week onwards), especially if it is known that they have an old anterior-wall infarct.", "contents": "[Results of pacing after acute myocardial infarction (author's transl)]. Indications for electrical pacing were present in 58 of 665 patients with acute myocardial infarction (8.7%). Posterior-wall infarction had occurred in 34, anterior-wall infarction in 20, while two had combined infarction and in a further two precise localisation was not possible. There were 16 deaths (27.6%), six of them with posterior-wall and nine with anterior-wall infarction. Bradycardic arrhythmias with A-V block predominated among posterior-wall infarctions, hemiblocks and bifascicular block in anterior-wall infarctions. Permanent pacing was practised in 14 patients, 11 with posterior and three with anterior-wall infarctions, i.e. permanent pacing was four times as common after posterior than anterior-wall infarctions, the proportion being 2:1 for temporary pacing, largely due to a higher mortality-rate after anterior-wall infarction. Old anterior-wall scars were present in nine of eleven patients with permanent pacing. Because of the danger of late bradycardia or A-V block patients with posterior-wall infarction should be carefully followed in the late phase (from about the third week onwards), especially if it is known that they have an old anterior-wall infarct."} {"id": "PMID:1261363", "title": "[Cytogenetic and clinical findings in suspected Turner's syndrome: results of a five-year study of 207 patients (author's transl)].", "content": "The hallmark of Turner's syndrome is small stature, primary amenorrhoea with delayed puberty and other congenital defects. Cytogenetic examinations were done over a five-year period of 207 patients of different ages. The diagnosis of Turner's syndrome was confirmed by karyotype in 94 (45.4%), tentatively confirmed by X-chromatin in 11 (5.3%) and in 21 (10.1%) with other disorders involving disturbed sexual development. In 73 cases Turner's syndrome was excluded and in nine the investigation had not been completed by the end of the study. There was a wide spectrum of clinical and cytogenetic findings in the 94 patients with cytogenetically confirmed Turner's syndrome: 50 (53.2%) had karyotype 45,X0; 25 (26.6%) X0/XX mosaic; 19 (20.2%) X-chromosomal structural anomalies with or without additional X0 cell line.", "contents": "[Cytogenetic and clinical findings in suspected Turner's syndrome: results of a five-year study of 207 patients (author's transl)]. The hallmark of Turner's syndrome is small stature, primary amenorrhoea with delayed puberty and other congenital defects. Cytogenetic examinations were done over a five-year period of 207 patients of different ages. The diagnosis of Turner's syndrome was confirmed by karyotype in 94 (45.4%), tentatively confirmed by X-chromatin in 11 (5.3%) and in 21 (10.1%) with other disorders involving disturbed sexual development. In 73 cases Turner's syndrome was excluded and in nine the investigation had not been completed by the end of the study. There was a wide spectrum of clinical and cytogenetic findings in the 94 patients with cytogenetically confirmed Turner's syndrome: 50 (53.2%) had karyotype 45,X0; 25 (26.6%) X0/XX mosaic; 19 (20.2%) X-chromosomal structural anomalies with or without additional X0 cell line."} {"id": "PMID:1261364", "title": "[Causes of electrode dislocation with transvenous pacemaker implantation (author's transl)].", "content": "The relationship between electrode dislocation and operative circumstances and case details was investigated in 486 patients who had pacemakers implanted. Electrode dislocation was more common among women and unrelated to age. The greater the operator's experience the lower the dislocation rate. Best results were obtained when implantation was performed via the left cephalic vein. There was a close relationship between threshold measurement obtained at the time of electrode placement and the frequency of dislocation.", "contents": "[Causes of electrode dislocation with transvenous pacemaker implantation (author's transl)]. The relationship between electrode dislocation and operative circumstances and case details was investigated in 486 patients who had pacemakers implanted. Electrode dislocation was more common among women and unrelated to age. The greater the operator's experience the lower the dislocation rate. Best results were obtained when implantation was performed via the left cephalic vein. There was a close relationship between threshold measurement obtained at the time of electrode placement and the frequency of dislocation."} {"id": "PMID:1261365", "title": "[Cystinosis, hyperparathyroidism and metastatic calcifications (author's transl)].", "content": "An 11-year-old boy died from uraemia in the course of cystinosis. In addition to the renal lesions common to this disease he had also developed nodular hyperplasia of the parathyroids and widespread extra-osseous calcifications in lungs, kidneys, stomach, the muscular arteries, skin and subcutaneous tissue. The calcifications and other features suggest that the hyperparathyroidism was a \"tertiary\" one, although this term is not generally accepted. The unusual cutaneous calcifications were probably due to calciphylaxis. As in this case, hyperparathyroidism and calcinosis can develop into a \"second disease\" which, due to the cystinosis, may follow a remarkably autonomous course.", "contents": "[Cystinosis, hyperparathyroidism and metastatic calcifications (author's transl)]. An 11-year-old boy died from uraemia in the course of cystinosis. In addition to the renal lesions common to this disease he had also developed nodular hyperplasia of the parathyroids and widespread extra-osseous calcifications in lungs, kidneys, stomach, the muscular arteries, skin and subcutaneous tissue. The calcifications and other features suggest that the hyperparathyroidism was a \"tertiary\" one, although this term is not generally accepted. The unusual cutaneous calcifications were probably due to calciphylaxis. As in this case, hyperparathyroidism and calcinosis can develop into a \"second disease\" which, due to the cystinosis, may follow a remarkably autonomous course."} {"id": "PMID:1261372", "title": "[Occupational allergy due to inhalation of pollen from Euphorbia fulgens Karw (author's transl)].", "content": "The increased cultivation and sales of Euphorbia fulgens Karw., originating in Mexico, has in the last few years led to occupational allergy, type I, in three growers manifesting itself as nasal disease, tracheobronchitis or bronchial asthma. Intracutaneous tests with pollen extracts were positive in all cases, even at high dilution. A specific hyposensitisation regimen, conducted over five months, gave highly promising results in one patient who had no symptoms in the following season, despite similar exposure. Such sensitisation by pollens of Euphorbia fulgens Karw. is probably widespread among growers and florists. The allergen is found only in the pollen, not in other parts of the plant. There is no relation to the toxic substances in the milk-sap of this plant family (Euphorbiaceae).", "contents": "[Occupational allergy due to inhalation of pollen from Euphorbia fulgens Karw (author's transl)]. The increased cultivation and sales of Euphorbia fulgens Karw., originating in Mexico, has in the last few years led to occupational allergy, type I, in three growers manifesting itself as nasal disease, tracheobronchitis or bronchial asthma. Intracutaneous tests with pollen extracts were positive in all cases, even at high dilution. A specific hyposensitisation regimen, conducted over five months, gave highly promising results in one patient who had no symptoms in the following season, despite similar exposure. Such sensitisation by pollens of Euphorbia fulgens Karw. is probably widespread among growers and florists. The allergen is found only in the pollen, not in other parts of the plant. There is no relation to the toxic substances in the milk-sap of this plant family (Euphorbiaceae)."} {"id": "PMID:1261373", "title": "[Morphological and clinical results after combined hormone and radiation therapy for carcinoma of the prostate (author's transl)].", "content": "83 prostatic carcinomas were analysed morphologically and clinically before and after combined therapy. The classification of these tumors is based on the proliferation pattern resulting in a group with only one and a group with a variety of growth patterns. The largest groups were carcinomas with glandular structures. On the basis of multiple biopsies the histologic regression of the tumors was determined. In 71% of the cases there was good agreement of morphological results and local palpation findings. Further analyses revealed a correlation between histological growth pattern of the carcinomas and degree of regression: prostatic carcinomas with glandular pattern showed more often a good regression after combined therapy than solid and(or) cribriform tumors. In the groups with a variety of structural pattern the degree of regression was dependent on the prevailing tumor structure. According to these results the organoid-glandular carcinomas of prostate are prognostically more favourable than all the other proliferation patterns. Nevertheless in a single case a prognosis of the therapeutic effect based only on the tumor differentiation can not be made.", "contents": "[Morphological and clinical results after combined hormone and radiation therapy for carcinoma of the prostate (author's transl)]. 83 prostatic carcinomas were analysed morphologically and clinically before and after combined therapy. The classification of these tumors is based on the proliferation pattern resulting in a group with only one and a group with a variety of growth patterns. The largest groups were carcinomas with glandular structures. On the basis of multiple biopsies the histologic regression of the tumors was determined. In 71% of the cases there was good agreement of morphological results and local palpation findings. Further analyses revealed a correlation between histological growth pattern of the carcinomas and degree of regression: prostatic carcinomas with glandular pattern showed more often a good regression after combined therapy than solid and(or) cribriform tumors. In the groups with a variety of structural pattern the degree of regression was dependent on the prevailing tumor structure. According to these results the organoid-glandular carcinomas of prostate are prognostically more favourable than all the other proliferation patterns. Nevertheless in a single case a prognosis of the therapeutic effect based only on the tumor differentiation can not be made."} {"id": "PMID:1261378", "title": "[Serial studies of the long-term effects of a total-fasting regimen (author's transl)].", "content": "The long-term results of total fasting during hospitalisation were evaluated an average of 21 months after the end of the hospital stay in 42 patients treated for obesity between 1971 and 1975. Further weight reduction occurred in 14, while the remainder had regained some weight. Nine of the latter had, in fact, surpassed their prehospitalisation weight. Neither age not sex, social status, time interval since fasting had any influence on the long-term results of total fasting. It is concluded that, in view of the poor correlation between cost and long-term result of such total-fasting regimen, it should be undertaken in this form only exceptionally.", "contents": "[Serial studies of the long-term effects of a total-fasting regimen (author's transl)]. The long-term results of total fasting during hospitalisation were evaluated an average of 21 months after the end of the hospital stay in 42 patients treated for obesity between 1971 and 1975. Further weight reduction occurred in 14, while the remainder had regained some weight. Nine of the latter had, in fact, surpassed their prehospitalisation weight. Neither age not sex, social status, time interval since fasting had any influence on the long-term results of total fasting. It is concluded that, in view of the poor correlation between cost and long-term result of such total-fasting regimen, it should be undertaken in this form only exceptionally."} {"id": "PMID:1261379", "title": "[Operative treatment of ulcerative colitis, Crohn's disease and diverticulitis (author's transl)].", "content": "Operations and follow-up examinations were conducted on 106 patient with ulcerative colitis, 33 with colitis Crohn, and 163 with diverticulitis, at the University Clinics of Cologne and Munich. Overall mortality rates were 24.5% (n=26), 6.1% (n=2) and 16% (n=26), respectively. In the surgical treatment of ulcerative colitis the possibility of malignant degeneration and, in the case of Crohn's disease, prevention of recurrences must be taken into consideration. Whether Crohn's disease is a precancerous condition remains to be clarified. Choosing the optimal time for operative intervention is as important in diverticulitis as in ulcerative colitis. Because of the possibility of complications and the high risk of operation, early intervention is recommended for diverticulitis.", "contents": "[Operative treatment of ulcerative colitis, Crohn's disease and diverticulitis (author's transl)]. Operations and follow-up examinations were conducted on 106 patient with ulcerative colitis, 33 with colitis Crohn, and 163 with diverticulitis, at the University Clinics of Cologne and Munich. Overall mortality rates were 24.5% (n=26), 6.1% (n=2) and 16% (n=26), respectively. In the surgical treatment of ulcerative colitis the possibility of malignant degeneration and, in the case of Crohn's disease, prevention of recurrences must be taken into consideration. Whether Crohn's disease is a precancerous condition remains to be clarified. Choosing the optimal time for operative intervention is as important in diverticulitis as in ulcerative colitis. Because of the possibility of complications and the high risk of operation, early intervention is recommended for diverticulitis."} {"id": "PMID:1261380", "title": "[Malpositioning of venous catheters (author's transl)].", "content": "The position of 2467 intravenous catheters was controlled radiographically over a period of one year. In 22.5% the position needed correcting. In most cases it was sufficient to withdraw the catheter slightly. In 68 patients in whom the catheter had formed loops or had entered the jugular vein the position was corrected using a J-shaped guide wire and was successful in 63 cases. This method needs little time and equipment and saves the patients repeated venous punctures. Not including bacterial contamination of the catheter the complication rate of venous catheterisation was 2.6%.", "contents": "[Malpositioning of venous catheters (author's transl)]. The position of 2467 intravenous catheters was controlled radiographically over a period of one year. In 22.5% the position needed correcting. In most cases it was sufficient to withdraw the catheter slightly. In 68 patients in whom the catheter had formed loops or had entered the jugular vein the position was corrected using a J-shaped guide wire and was successful in 63 cases. This method needs little time and equipment and saves the patients repeated venous punctures. Not including bacterial contamination of the catheter the complication rate of venous catheterisation was 2.6%."} {"id": "PMID:1261381", "title": "[Atrial flutter with an audible atrial sound (author's transl)].", "content": "In a case of rheumatic valve disease atrial sounds could be heard and recorded on the phonocardiogram during atrial flutter at a rate of 260/min and an atrioventricular block of 3:1 and 5:1. The atrial flutter sounds were also recorded in the apex-cardiogram and as a slight but rapid motion of the anterior mitral valve leaflet in the echocardiogram. These atrial sounds were recorded both in systole and diastole and disappeared after cardiac failure had been treated and sinus rhythm restored. This case and 19 others reported in the medical literature indicate that for atrial sounds to become audible requires high-grade atrioventricular block and increased atrial contractions with increased ventricular filling. The sounds have been proven to originate in the atrium, the characteristics of the sound being similar to those of an opening snap.", "contents": "[Atrial flutter with an audible atrial sound (author's transl)]. In a case of rheumatic valve disease atrial sounds could be heard and recorded on the phonocardiogram during atrial flutter at a rate of 260/min and an atrioventricular block of 3:1 and 5:1. The atrial flutter sounds were also recorded in the apex-cardiogram and as a slight but rapid motion of the anterior mitral valve leaflet in the echocardiogram. These atrial sounds were recorded both in systole and diastole and disappeared after cardiac failure had been treated and sinus rhythm restored. This case and 19 others reported in the medical literature indicate that for atrial sounds to become audible requires high-grade atrioventricular block and increased atrial contractions with increased ventricular filling. The sounds have been proven to originate in the atrium, the characteristics of the sound being similar to those of an opening snap."} {"id": "PMID:1261387", "title": "[Clinical features and course of congestive cardiomyopathy of unknown aetiology (author's transl)].", "content": "Clinical, haemodynamic and angiographic findings in 50 patients with congestive cardiomyopathy were related to subsequent clinical course (mean observation period of 40 months). Ejection fraction and changes in mean pulmonary \"wedge\" pressure on ergometric exercise proved to be the most reliable criteria for judging left-ventricular function. During the period of observation 11 patients had died, in 15 the clinical state had deteriorated by one or two functional classes, and in 24 there had been no change. Patients with progressing disease differed from those clinically unchanged by having a smaller cardiac index, increased end-diastolic left ventricular pressure, higher pulmonary arterial pressure and smaller ejection fraction. Prognosis was no worse with atrial fibrillation than with sinus rhythm. Four of 13 patients with left bundle branch block died during the observation period and in seven the clinical state had deteriorated by one or two functional classes. The tested variables apparently have a good prognostic value.", "contents": "[Clinical features and course of congestive cardiomyopathy of unknown aetiology (author's transl)]. Clinical, haemodynamic and angiographic findings in 50 patients with congestive cardiomyopathy were related to subsequent clinical course (mean observation period of 40 months). Ejection fraction and changes in mean pulmonary \"wedge\" pressure on ergometric exercise proved to be the most reliable criteria for judging left-ventricular function. During the period of observation 11 patients had died, in 15 the clinical state had deteriorated by one or two functional classes, and in 24 there had been no change. Patients with progressing disease differed from those clinically unchanged by having a smaller cardiac index, increased end-diastolic left ventricular pressure, higher pulmonary arterial pressure and smaller ejection fraction. Prognosis was no worse with atrial fibrillation than with sinus rhythm. Four of 13 patients with left bundle branch block died during the observation period and in seven the clinical state had deteriorated by one or two functional classes. The tested variables apparently have a good prognostic value."} {"id": "PMID:1261388", "title": "[Myocardial bridge - cause of cardiac phase-dependent coronary stenosis (author's transl)].", "content": "A 41 year-old man presented with anginal pain and a positive exercise electrocardiogram. Hemodynamic and angiographic evaluation disclosed mild hypertrophic obstructive cardiomyopathy and a conic stenosis of the proximal left anterior descending artery confined to the systolic phase of the heart action. The degree of constriction of the coronary artery was no longer evident. Pathophysiologic consequences suggest that surgical dissection of muscle bridges should be considered in symptomatic patients with severe coronary obstruction.", "contents": "[Myocardial bridge - cause of cardiac phase-dependent coronary stenosis (author's transl)]. A 41 year-old man presented with anginal pain and a positive exercise electrocardiogram. Hemodynamic and angiographic evaluation disclosed mild hypertrophic obstructive cardiomyopathy and a conic stenosis of the proximal left anterior descending artery confined to the systolic phase of the heart action. The degree of constriction of the coronary artery was no longer evident. Pathophysiologic consequences suggest that surgical dissection of muscle bridges should be considered in symptomatic patients with severe coronary obstruction."} {"id": "PMID:1261389", "title": "[Changes of left ventricular transverse diameter and of contractility after haemodialysis (author's transl)].", "content": "In 26 patients (8 women, 18 men; mean age 47 +/- 3 years) who participated in a regular dialysis programme twice weekly the left ventricular diameter, the mean velocity of fibre shortening, the ventricular wall thickness, and the muscle mass were determined echocardiographically. Left ventricular muscle mass (187 +/- 13 g), left ventricular posterobasal wall thickness (14,7 +/- 0,6 mm) and septal thickness (16,4 +/- 0,8 mm) were pathologically increased due to chronic pressure and volume overloading. After an average dialysis time of 12 hours the body weight was reduced by 2,6 +/- 0,4 kg (+ 1,0 to -7,8 kg). The left ventricular transverse diameter changed from 55,3 to 50,2 mm (P less than 0,001) which correlated with a decrease of the enddiastolic volume from 160 +/- 11 to 125 +/- 10 ml (P less than 0,01(. Despite increased cardiac frequency and unchanged diastolic and systolic pressure no significant increase of the mean velocity of fibre shortening (0,93 +/- 0,06 vector 1,13 +/- 0,09 circ/s) occurred. The results show that loss of fluid during haemodialysis led to a significant decrease of the enddiastolic transverse diameter and the enddiastolic left ventricular volume. However, dialysis does not lead to an increase of the mean velocity of fibre shortening as a parameter of improved contractility.", "contents": "[Changes of left ventricular transverse diameter and of contractility after haemodialysis (author's transl)]. In 26 patients (8 women, 18 men; mean age 47 +/- 3 years) who participated in a regular dialysis programme twice weekly the left ventricular diameter, the mean velocity of fibre shortening, the ventricular wall thickness, and the muscle mass were determined echocardiographically. Left ventricular muscle mass (187 +/- 13 g), left ventricular posterobasal wall thickness (14,7 +/- 0,6 mm) and septal thickness (16,4 +/- 0,8 mm) were pathologically increased due to chronic pressure and volume overloading. After an average dialysis time of 12 hours the body weight was reduced by 2,6 +/- 0,4 kg (+ 1,0 to -7,8 kg). The left ventricular transverse diameter changed from 55,3 to 50,2 mm (P less than 0,001) which correlated with a decrease of the enddiastolic volume from 160 +/- 11 to 125 +/- 10 ml (P less than 0,01(. Despite increased cardiac frequency and unchanged diastolic and systolic pressure no significant increase of the mean velocity of fibre shortening (0,93 +/- 0,06 vector 1,13 +/- 0,09 circ/s) occurred. The results show that loss of fluid during haemodialysis led to a significant decrease of the enddiastolic transverse diameter and the enddiastolic left ventricular volume. However, dialysis does not lead to an increase of the mean velocity of fibre shortening as a parameter of improved contractility."} {"id": "PMID:1261390", "title": "[Radiotelemetry of cardiovascular response on a fitness trail (author's transl)].", "content": "Continuous radiotelemetry of direct arterial blood pressure and heart rate was performed in eight healthy subjects (seven men, one woman; average age 26 years) on a fitness trail. The results demonstrate that such running represents a maximal effort, at 192/min heart rate (age-related maximum). The heart rate remained constant whether on largely dynamic exercise during running or on largely static effort during gymnastic exercise. During running, blood pressure rose up to 151/79 mm Hg, while gymnastic exercise gave mean values of up to 200/130 mm Hg as a result of sustained muscle contractions and forced breathing. Such uncontrolled maximal effort may be unexpectedly dangerous to persons with cardiovascular disease and fitness trails should not be recommended in the rehabilitation of cardiac patients.", "contents": "[Radiotelemetry of cardiovascular response on a fitness trail (author's transl)]. Continuous radiotelemetry of direct arterial blood pressure and heart rate was performed in eight healthy subjects (seven men, one woman; average age 26 years) on a fitness trail. The results demonstrate that such running represents a maximal effort, at 192/min heart rate (age-related maximum). The heart rate remained constant whether on largely dynamic exercise during running or on largely static effort during gymnastic exercise. During running, blood pressure rose up to 151/79 mm Hg, while gymnastic exercise gave mean values of up to 200/130 mm Hg as a result of sustained muscle contractions and forced breathing. Such uncontrolled maximal effort may be unexpectedly dangerous to persons with cardiovascular disease and fitness trails should not be recommended in the rehabilitation of cardiac patients."} {"id": "PMID:1261391", "title": "[Influence of radio and television sets on implanted cardiac pacemakers (author's transl)].", "content": "Investigations done on implanted pacemakers with a low threshold against extraneous signals and in-vitro tests under suitable conditions both showed that pacemaker wearers may go near television and accessories such as ultrsound distant control or flexless infrared ear phones without any danger. Radio and television sets are fitted to an increasing degree with electronic sensor switches which initiate various functions after a slight touch. This satisfies present regulations of German Electrical Engineers concerning permitted contact currents. However, pacemaker patients can cause impulse defects by use of sensor switches provided the contact current is less than 25 muA. Sensor technique will in the future be introduced for everyday use on a large scale. Therefore, pacemaker patients should be alerted to the possibilities of an influence, and industry should be made to reduce contact currents in sensors to values below 20 muA.", "contents": "[Influence of radio and television sets on implanted cardiac pacemakers (author's transl)]. Investigations done on implanted pacemakers with a low threshold against extraneous signals and in-vitro tests under suitable conditions both showed that pacemaker wearers may go near television and accessories such as ultrsound distant control or flexless infrared ear phones without any danger. Radio and television sets are fitted to an increasing degree with electronic sensor switches which initiate various functions after a slight touch. This satisfies present regulations of German Electrical Engineers concerning permitted contact currents. However, pacemaker patients can cause impulse defects by use of sensor switches provided the contact current is less than 25 muA. Sensor technique will in the future be introduced for everyday use on a large scale. Therefore, pacemaker patients should be alerted to the possibilities of an influence, and industry should be made to reduce contact currents in sensors to values below 20 muA."} {"id": "PMID:1261397", "title": "[Collagen peptidase in Crohn's disease].", "content": "Collagen-peptidase activity in serum was increased in 54 of 71 cases of Crohn's disease. This increase was highly significant (P less than 0.001) compared with the results in a control group (24 cases). Immunosuppressive drugs (corticosteroids, azathioprine) decreased collagen-peptidase activity in the patients with Crohn's disease. On average it was higher than that of patients with sarcoidosis. Further tests are required to establish whether collagen-peptidase activity is of diagnostic value in Crohn's disease.", "contents": "[Collagen peptidase in Crohn's disease]. Collagen-peptidase activity in serum was increased in 54 of 71 cases of Crohn's disease. This increase was highly significant (P less than 0.001) compared with the results in a control group (24 cases). Immunosuppressive drugs (corticosteroids, azathioprine) decreased collagen-peptidase activity in the patients with Crohn's disease. On average it was higher than that of patients with sarcoidosis. Further tests are required to establish whether collagen-peptidase activity is of diagnostic value in Crohn's disease."} {"id": "PMID:1261398", "title": "[Serological hepatitis B characteristics in clinical laboratory control sera].", "content": "99 samples of 29 different reference sera were tested for HBs-antigen and anti-HBs radioimmunologically and by means of counter-current electrophoresis. 4 of 99 (4%) of the samples and 4 of 29 (14%) of the reference sera were HBs-antigen positive. 45 of 99 (45%) of the samples and 5 of 29 (17%) of the reference sera were anti-HBs positive. Reference sera are an additional risk for hepatitis in clinical laboratories and must be considered potentially infectious.", "contents": "[Serological hepatitis B characteristics in clinical laboratory control sera]. 99 samples of 29 different reference sera were tested for HBs-antigen and anti-HBs radioimmunologically and by means of counter-current electrophoresis. 4 of 99 (4%) of the samples and 4 of 29 (14%) of the reference sera were HBs-antigen positive. 45 of 99 (45%) of the samples and 5 of 29 (17%) of the reference sera were anti-HBs positive. Reference sera are an additional risk for hepatitis in clinical laboratories and must be considered potentially infectious."} {"id": "PMID:1261399", "title": "[Prevention of HBs antigen-positive serum hepatitis with hyperimmune-globulin anti-HBs].", "content": "Selection of donors to prevent HBs-antigen positive serum hepatitis has been only partially successful. For this reason the attempt was made to prevent the disease by passive immunisation with anti-HBs antibodies. A prerequisite for the systematic use of such immunisation is the determination of antibody threshold which would still provide protection. Plasma elimination of transmitted. HBs antibodies was serially measured in five children with terminal renal failure and ten normal subjects after intensive contact with HBs antibodies. Half-life values indicated marked individual variations which have to be taken into account with long-term prophylaxis. In the children they were 28.5, 25.9, 16.6, 11.7 and 7.8 days, respectively. In the healthy subjects the half-life averaged 20.3 days. The long-term programme developed by the authors appears to be suitable for revealing the value of hyperimmune-globulin anti-HBs in the prevention of HBs-antigen positive serum hepatitis.", "contents": "[Prevention of HBs antigen-positive serum hepatitis with hyperimmune-globulin anti-HBs]. Selection of donors to prevent HBs-antigen positive serum hepatitis has been only partially successful. For this reason the attempt was made to prevent the disease by passive immunisation with anti-HBs antibodies. A prerequisite for the systematic use of such immunisation is the determination of antibody threshold which would still provide protection. Plasma elimination of transmitted. HBs antibodies was serially measured in five children with terminal renal failure and ten normal subjects after intensive contact with HBs antibodies. Half-life values indicated marked individual variations which have to be taken into account with long-term prophylaxis. In the children they were 28.5, 25.9, 16.6, 11.7 and 7.8 days, respectively. In the healthy subjects the half-life averaged 20.3 days. The long-term programme developed by the authors appears to be suitable for revealing the value of hyperimmune-globulin anti-HBs in the prevention of HBs-antigen positive serum hepatitis."} {"id": "PMID:1261400", "title": "[Frequency of chronic non-suppurative destructive cholangitis and primary biliary cirrhosis in comparison with other chronic inflammatory liver diseases].", "content": "Primary biliary liver disease was diagnosed and verified by histology and demonstration of antibodies against mitochondrial proteins in 73 patients between 1970 and 1974. Comparing cases between 1950 and 1961 and between 1970 and 1974 with the frequency of other chronic inflammatory liver diseases it was found that figures for advanced primary biliary cirrhosis remained unchanged during both periods whereas early stages of primary biliary disease were detected far more frequently in the latter period. One case with chronic non-suppurative destructive cholangitis or complete primary biliary cirrhosis was outnumbered by 8 cases of chronic aggressive hepatitis and 15 of liver cirrhosis of various aetiologies in Kassel. The relations in G\u00f6ttingen were 1 : 5 and 1 : 6, respectively. Primary biliary diseases are no longer rare.", "contents": "[Frequency of chronic non-suppurative destructive cholangitis and primary biliary cirrhosis in comparison with other chronic inflammatory liver diseases]. Primary biliary liver disease was diagnosed and verified by histology and demonstration of antibodies against mitochondrial proteins in 73 patients between 1970 and 1974. Comparing cases between 1950 and 1961 and between 1970 and 1974 with the frequency of other chronic inflammatory liver diseases it was found that figures for advanced primary biliary cirrhosis remained unchanged during both periods whereas early stages of primary biliary disease were detected far more frequently in the latter period. One case with chronic non-suppurative destructive cholangitis or complete primary biliary cirrhosis was outnumbered by 8 cases of chronic aggressive hepatitis and 15 of liver cirrhosis of various aetiologies in Kassel. The relations in G\u00f6ttingen were 1 : 5 and 1 : 6, respectively. Primary biliary diseases are no longer rare."} {"id": "PMID:1261401", "title": "[Intrahepatic cholestasis due to N-propyl ajmaline].", "content": "In two patients intrahepatic cholestasis and cholestatic liver disease probably due to N-propyl ajmaline were observed. In both cases there was a four-week-interval between the first ingestion of the drug and the onset of jaundice. In one case with rigors there was a temporary rise in temperature and cholestasis. In the other there was a two to three week prodromal period of pruritus and gastro-intestinal symptoms. Both cases were characterised by blood and pronounced tissue eosinophilia in the periportal zones, a marked increase of cholestatic and hepatic cell enzymes, serum bilirubin and cholesterol, a moderate increase in erythrocyte sedimentation rate and absence of leucocytosis. Pathological laboratory findings returned to normal spontaneously within 5 weeks in one case and within two weeks under steroid therapy in the other.", "contents": "[Intrahepatic cholestasis due to N-propyl ajmaline]. In two patients intrahepatic cholestasis and cholestatic liver disease probably due to N-propyl ajmaline were observed. In both cases there was a four-week-interval between the first ingestion of the drug and the onset of jaundice. In one case with rigors there was a temporary rise in temperature and cholestasis. In the other there was a two to three week prodromal period of pruritus and gastro-intestinal symptoms. Both cases were characterised by blood and pronounced tissue eosinophilia in the periportal zones, a marked increase of cholestatic and hepatic cell enzymes, serum bilirubin and cholesterol, a moderate increase in erythrocyte sedimentation rate and absence of leucocytosis. Pathological laboratory findings returned to normal spontaneously within 5 weeks in one case and within two weeks under steroid therapy in the other."} {"id": "PMID:1261402", "title": "[Differences in taste assessment of sweeteners by normal and overweight persons].", "content": "Taste assessment was tested in 20 obese and 20 normal-weight in-patients using watery solutions of saccharose and three synthetic sweeteners. Each patient was asked to assess ten different taste qualities of each solution on a point scale. There were highly significant differences between the two groups of subjects. The difference was especially marked for the categories \"synthetic - natural\", \"unpleasant - very tasty\", and \"changeable - stable in times\". These findings suggest changes in physical or central taste sensation in obese persons. This view is supported by their decreased ability to differentiate between saccharose and any sweetener. The results further support substituting sweetening agents for sugar in reducing diets.", "contents": "[Differences in taste assessment of sweeteners by normal and overweight persons]. Taste assessment was tested in 20 obese and 20 normal-weight in-patients using watery solutions of saccharose and three synthetic sweeteners. Each patient was asked to assess ten different taste qualities of each solution on a point scale. There were highly significant differences between the two groups of subjects. The difference was especially marked for the categories \"synthetic - natural\", \"unpleasant - very tasty\", and \"changeable - stable in times\". These findings suggest changes in physical or central taste sensation in obese persons. This view is supported by their decreased ability to differentiate between saccharose and any sweetener. The results further support substituting sweetening agents for sugar in reducing diets."} {"id": "PMID:1261403", "title": "[Coincidence of Hodgkin's disease and epithelioid-cell granulomatosis in liver and spleen].", "content": "Two of seventy patients with Hodgkin's disease who had exploratory laparotomy with liver biopsy and splenectomy were found to have extensive epithelioid-cell granulomas in liver and spleen. The coincidence of malignant tumour and epithelioid-cell granulomas of liver and spleen without lymph-node involvement is unusual. Knowing of the coincidence of Hodgkin's disease and such granulomas is clinically important because extensive diagnostic measures, including biopsy, are necessary in the differential diagnosis, and the patient's prognosis will depend on the therapeutic measures taken.", "contents": "[Coincidence of Hodgkin's disease and epithelioid-cell granulomatosis in liver and spleen]. Two of seventy patients with Hodgkin's disease who had exploratory laparotomy with liver biopsy and splenectomy were found to have extensive epithelioid-cell granulomas in liver and spleen. The coincidence of malignant tumour and epithelioid-cell granulomas of liver and spleen without lymph-node involvement is unusual. Knowing of the coincidence of Hodgkin's disease and such granulomas is clinically important because extensive diagnostic measures, including biopsy, are necessary in the differential diagnosis, and the patient's prognosis will depend on the therapeutic measures taken."} {"id": "PMID:1261410", "title": "[Results of gastric lymphography with particular reference to gastric carcinoma (author's transl)].", "content": "The regional lymph nodes of the stomach can be visualised radiologically by injecting Lipiodol Ultra-Fluid into the submucous layer of the stomach wall through a gastroscope. Lymphography was performed in gastrologically healthy probands (n = 10), in patients with gastroduodenal ulceration (n = 17), and in patients with gastric carcinoma (n = 35). In 28 of the gastric carcinoma patients the first order lymph nodes were demonstrated, in 21 cases the second order and in 15 cases the third order whereas defects in uptake indicated metastases in 16 patients which could be histologically confirmed in 13. Gastric lymphography may contribute to the indication for operation if metastases are suspected in the second and third order lymph nodes as nodes along the upper border of the pancreas and the coeliac trunk are very difficult to remove radically.", "contents": "[Results of gastric lymphography with particular reference to gastric carcinoma (author's transl)]. The regional lymph nodes of the stomach can be visualised radiologically by injecting Lipiodol Ultra-Fluid into the submucous layer of the stomach wall through a gastroscope. Lymphography was performed in gastrologically healthy probands (n = 10), in patients with gastroduodenal ulceration (n = 17), and in patients with gastric carcinoma (n = 35). In 28 of the gastric carcinoma patients the first order lymph nodes were demonstrated, in 21 cases the second order and in 15 cases the third order whereas defects in uptake indicated metastases in 16 patients which could be histologically confirmed in 13. Gastric lymphography may contribute to the indication for operation if metastases are suspected in the second and third order lymph nodes as nodes along the upper border of the pancreas and the coeliac trunk are very difficult to remove radically."} {"id": "PMID:1261411", "title": "[Clinical features and surgical treatment of carcinoma of the pancreas (author's transl)].", "content": "From 1964 to 1975 a total of 338 patients were operated on for pancreatic cancer. Duodenopancreatectomy was performed in 69 (20%), at a postoperative death rate of 16%. Second look operations proved to be worthwhile. Thus the resection rate after first operations elsewhere was 27%. Five patients lived for more than five and 19 for more than two years after operation. Since 1971 30 patients have survived so far after radiacal operation.", "contents": "[Clinical features and surgical treatment of carcinoma of the pancreas (author's transl)]. From 1964 to 1975 a total of 338 patients were operated on for pancreatic cancer. Duodenopancreatectomy was performed in 69 (20%), at a postoperative death rate of 16%. Second look operations proved to be worthwhile. Thus the resection rate after first operations elsewhere was 27%. Five patients lived for more than five and 19 for more than two years after operation. Since 1971 30 patients have survived so far after radiacal operation."} {"id": "PMID:1261412", "title": "[Synovectomy in the prevention of recurrent joint bleedings in haemophilia (author's transl)].", "content": "Synovectomy was performed in seven patients with severe haemophilia A, one with moderately severe haemophilia A and one with severe haemophilia B. Frequently recurring haemorrhages into one knee and demonstrated hypertrophic synovitis were the indications for operation in all. No serious bleeding complications occurred during or after the operations. After synovectomy the frequency of haemarthroses in the synovectomised joint decreased significantly. Satisfactory joint function was eventually achieved in all by gymnastic exercises and physiotherapy over a long period. The operation should only be done in large haemophilia centres were there is sufficient experience.", "contents": "[Synovectomy in the prevention of recurrent joint bleedings in haemophilia (author's transl)]. Synovectomy was performed in seven patients with severe haemophilia A, one with moderately severe haemophilia A and one with severe haemophilia B. Frequently recurring haemorrhages into one knee and demonstrated hypertrophic synovitis were the indications for operation in all. No serious bleeding complications occurred during or after the operations. After synovectomy the frequency of haemarthroses in the synovectomised joint decreased significantly. Satisfactory joint function was eventually achieved in all by gymnastic exercises and physiotherapy over a long period. The operation should only be done in large haemophilia centres were there is sufficient experience."} {"id": "PMID:1261422", "title": "[Transverse axial computerized tomography (EMI scan): value and indications (author's transl)].", "content": "The results of transverse axial computerized tomography in EMI scan (transverse CAT) in 2 000 examinations are reviewed. The method was shown to enlarge significantly the diagnostic possibilities in cerebral disease. A correct identification of intracranial tumour was made in 98% of 250 cases. Cerebral haemorrhage, infarction and contusional oedema could be differentiated. Various forms and extensions of cerebral oedema were visualized as never before. Postoperative changes and the course of vascular disease, tumour or hydrocephalus after shunt were demonstrated at an early stage. The indications for pneumo-encephalography have been reduced to a few very special situations. On the other hand, angiography is still of decisive value in vascular cerebral disease and should be performed before surgery in case of space-occupying lesions.", "contents": "[Transverse axial computerized tomography (EMI scan): value and indications (author's transl)]. The results of transverse axial computerized tomography in EMI scan (transverse CAT) in 2 000 examinations are reviewed. The method was shown to enlarge significantly the diagnostic possibilities in cerebral disease. A correct identification of intracranial tumour was made in 98% of 250 cases. Cerebral haemorrhage, infarction and contusional oedema could be differentiated. Various forms and extensions of cerebral oedema were visualized as never before. Postoperative changes and the course of vascular disease, tumour or hydrocephalus after shunt were demonstrated at an early stage. The indications for pneumo-encephalography have been reduced to a few very special situations. On the other hand, angiography is still of decisive value in vascular cerebral disease and should be performed before surgery in case of space-occupying lesions."} {"id": "PMID:1261423", "title": "[The prodromal phase of myocardial infarction (author's transl)].", "content": "The prodromal phase was studied retrospectively in 101 patients who had sustained acute myocardial infarctions. Only in a few did the infarction occur suddenly. Prodromal symptoms occurred in 80%: angina pectoris of various forms, especially change in type of complaint, signs of heart failure and non-specific general symptoms. With approaching infarction, approximately from the third week onwards, there was a crescendo course of anginal symptoms and of heart failure. Especially typical was change in the form of the angina, with occurrence of spontaneous or resting angina or recumbent angina. Such anginal symptoms, without previous angina on effort, only occurred during the last seven days before the infarction. Angina with manifest or latent signs of heart failure in the course of increasing symptoms (crescendo course) was typical for the last three to four days before infarction. There was an increased incidence of prodromal signs in anterior-wall infarction. A crescendo course implied a worse prognosis. Prodromal symptoms are frequent and prognostically less favourable also in women.", "contents": "[The prodromal phase of myocardial infarction (author's transl)]. The prodromal phase was studied retrospectively in 101 patients who had sustained acute myocardial infarctions. Only in a few did the infarction occur suddenly. Prodromal symptoms occurred in 80%: angina pectoris of various forms, especially change in type of complaint, signs of heart failure and non-specific general symptoms. With approaching infarction, approximately from the third week onwards, there was a crescendo course of anginal symptoms and of heart failure. Especially typical was change in the form of the angina, with occurrence of spontaneous or resting angina or recumbent angina. Such anginal symptoms, without previous angina on effort, only occurred during the last seven days before the infarction. Angina with manifest or latent signs of heart failure in the course of increasing symptoms (crescendo course) was typical for the last three to four days before infarction. There was an increased incidence of prodromal signs in anterior-wall infarction. A crescendo course implied a worse prognosis. Prodromal symptoms are frequent and prognostically less favourable also in women."} {"id": "PMID:1261424", "title": "[Results of cancer screening in women (author's transl)].", "content": "The results of cancer screening in women were evaluated from 1,1 million investigations during the third quarter of 1971 to the second quarter of 1974. Positive cytological results of the uterine cervix were found in 0,39% on first investigation and in 0,38% on repeat investigations. Positive results in the breast amounted only to a quarter (0,1%) of the frequency of positive cytological results despite the fact that breast cancer occurs more frequently than cervical carcinoma. Only 0,03% positive findings were obtained by digital rectal palpation. The low incidence of the diseases sought for and the partly low sensitivity of the screening methods are responsible for the small numbers of positive findings in early detection investigations and are an indication of the effort involved. Participation of the population in investigations for early detection of cancer is unsatisfactory especially in older age groups with an increased risk.", "contents": "[Results of cancer screening in women (author's transl)]. The results of cancer screening in women were evaluated from 1,1 million investigations during the third quarter of 1971 to the second quarter of 1974. Positive cytological results of the uterine cervix were found in 0,39% on first investigation and in 0,38% on repeat investigations. Positive results in the breast amounted only to a quarter (0,1%) of the frequency of positive cytological results despite the fact that breast cancer occurs more frequently than cervical carcinoma. Only 0,03% positive findings were obtained by digital rectal palpation. The low incidence of the diseases sought for and the partly low sensitivity of the screening methods are responsible for the small numbers of positive findings in early detection investigations and are an indication of the effort involved. Participation of the population in investigations for early detection of cancer is unsatisfactory especially in older age groups with an increased risk."} {"id": "PMID:1261425", "title": "[Generalised herpes simplex virus infection presenting as an \"acute abdomen\" (author's transl)].", "content": "A 23-year-old patient developed acute upper abdominal symptoms during in-patient treatment for vulvo-vaginitis. Clinical picture, scintigraphy and angiography suggested a space-occupying process of the liver. Laparotomy showed ascites and a congested liver covered with cell necroses. The patient died the day after the operation from circulatory failure. Virological investigations of liver and spleen cell suspensions as well as the ascites fluid led to the demonstration of herpes virus type 2. The complement binding reaction gave a titre of 1:20 to herpes simplex virus. Disseminated herpes simplex virus infection is rare and in this case spread from the genital area.", "contents": "[Generalised herpes simplex virus infection presenting as an \"acute abdomen\" (author's transl)]. A 23-year-old patient developed acute upper abdominal symptoms during in-patient treatment for vulvo-vaginitis. Clinical picture, scintigraphy and angiography suggested a space-occupying process of the liver. Laparotomy showed ascites and a congested liver covered with cell necroses. The patient died the day after the operation from circulatory failure. Virological investigations of liver and spleen cell suspensions as well as the ascites fluid led to the demonstration of herpes virus type 2. The complement binding reaction gave a titre of 1:20 to herpes simplex virus. Disseminated herpes simplex virus infection is rare and in this case spread from the genital area."} {"id": "PMID:1261429", "title": "Drugs and gastric damage.", "content": "The effects of aspirin, salicylate formulations and substitutes, smoking (nicotine), indomethacin, corticosteroids, phenylbutazone, ethanol, caffeine and reserpine on the gastric mucosa are discussed. The damaging effects of the drugs are considered in terms of the gastric mucosal barrier, gastric erosions, microbleeding and haematemesis and melaena and finally whether they cause peptic ulcer. There is suggestive evidence that unbuffered aspirin is a cause of haematemesis and melaena and of gastric ulcer but the incidence rates for hospital admission are low, being 10 to 15 per 100,000 heavy users per year. Aspirin in solution as acetylsalicylate buffered to maintain a neutral pH protects against gastric damage. Newer aspirin substitutes (mefenamic acid, fenoprofen, naproxen, tolmetin and ibuprofen) appear to cause less faecal blood loss than aspirin but their long-term effects have not been fully evaluated. Smoking is definitely associated with peptic ucler but the mechanism is unknown. Corticosteroids are probably not ulcerogenic despite clinical bias that they are. Indomethacin and phenylbutazone may be ulcerogenic but there is insufficient evidence to make firm judgements. Ethanol, caffeine and reserpine, on available evidence, are probably not ulcerogenic.", "contents": "Drugs and gastric damage. The effects of aspirin, salicylate formulations and substitutes, smoking (nicotine), indomethacin, corticosteroids, phenylbutazone, ethanol, caffeine and reserpine on the gastric mucosa are discussed. The damaging effects of the drugs are considered in terms of the gastric mucosal barrier, gastric erosions, microbleeding and haematemesis and melaena and finally whether they cause peptic ulcer. There is suggestive evidence that unbuffered aspirin is a cause of haematemesis and melaena and of gastric ulcer but the incidence rates for hospital admission are low, being 10 to 15 per 100,000 heavy users per year. Aspirin in solution as acetylsalicylate buffered to maintain a neutral pH protects against gastric damage. Newer aspirin substitutes (mefenamic acid, fenoprofen, naproxen, tolmetin and ibuprofen) appear to cause less faecal blood loss than aspirin but their long-term effects have not been fully evaluated. Smoking is definitely associated with peptic ucler but the mechanism is unknown. Corticosteroids are probably not ulcerogenic despite clinical bias that they are. Indomethacin and phenylbutazone may be ulcerogenic but there is insufficient evidence to make firm judgements. Ethanol, caffeine and reserpine, on available evidence, are probably not ulcerogenic."} {"id": "PMID:1261485", "title": "[Gerstmann's syndrome (critical review of the literature)].", "content": "Serious doubts have been casted upon the validity of the Gerstmann's syndrome since the paper of Benton in 1961. On the other hand, the results of several recent works suggest that it could not be a mere artifact. The analysis of this results, and mostly the theoretical works of Luria on the physiology of higher cortical functions, make it possible to imagine a functional unity behind the heterogenous signs of this syndrom, and the other manifestations of left parieto-occipital lesions. The data collected in the litterature are discussed, with special reference to the theoretical implications of Gerstmann's syndrome.", "contents": "[Gerstmann's syndrome (critical review of the literature)]. Serious doubts have been casted upon the validity of the Gerstmann's syndrome since the paper of Benton in 1961. On the other hand, the results of several recent works suggest that it could not be a mere artifact. The analysis of this results, and mostly the theoretical works of Luria on the physiology of higher cortical functions, make it possible to imagine a functional unity behind the heterogenous signs of this syndrom, and the other manifestations of left parieto-occipital lesions. The data collected in the litterature are discussed, with special reference to the theoretical implications of Gerstmann's syndrome."} {"id": "PMID:1261486", "title": "[Effect of psychotropic drugs on physiological variations and psychometric scores during attention].", "content": "A study was undertaken to determine the activation profile and psychometric performances in 10 adult volunteer subjects. The activation profile was evaluated by measuring heart and respiratory rates and also the H reflex (motor response). Psychometric performances during two attention tests were measured by the subjects' scores. The subjects were then submitted to a per os psychotrope drug treatment at a liminar therapeutic dose. Psychometric performances were decreased in subjects given a strong psychoactivator drug (amphetamine, genozolone), while they could be increased to an optimal level with a less active psycho-activation (Pyrisuccid\u00e9anol). Under the same conditions, the motor response, tested using the H-reflex, varied in the same way as the psychometric performance curve. However, the cardiac and respiratory rates show changes induced by the administered drugs. These results show some conditions were performance and activation are dissociated under the effect of psycho-active drugs.", "contents": "[Effect of psychotropic drugs on physiological variations and psychometric scores during attention]. A study was undertaken to determine the activation profile and psychometric performances in 10 adult volunteer subjects. The activation profile was evaluated by measuring heart and respiratory rates and also the H reflex (motor response). Psychometric performances during two attention tests were measured by the subjects' scores. The subjects were then submitted to a per os psychotrope drug treatment at a liminar therapeutic dose. Psychometric performances were decreased in subjects given a strong psychoactivator drug (amphetamine, genozolone), while they could be increased to an optimal level with a less active psycho-activation (Pyrisuccid\u00e9anol). Under the same conditions, the motor response, tested using the H-reflex, varied in the same way as the psychometric performance curve. However, the cardiac and respiratory rates show changes induced by the administered drugs. These results show some conditions were performance and activation are dissociated under the effect of psycho-active drugs."} {"id": "PMID:1261487", "title": "Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat.", "content": "Sequential blood samples were obtained from undisturbed freely-behaving male rats bearing chronic intracardiac venous cannulae. Blood was withdrawn every 15 min for periods of 4-24 h; plasma was separated, and saline-resuspended red cells were reinjected. Plasma GH was determined by radioimmunoassay. Pulsatile GH secretion was evident in each animal with most peak values greater than 200 ng/ml and most trough values less than ng/ml. The GH secretory episodes occurred at approximately 3 h intervals, and this rhythmic pattern of GH secretion persisted unchanged across all phases of a 12-h light-dark (L-D) cycle. Seven major episodes of GH secretion were observed during a single 24-h period. The mean period, or time interval between episodes, in 24 animals was 3.32 +/- 0.07 (SEM)h. The timing of the pulses with respect to the L-D cycle was similar in most animals, indicating that the rhythm may be entrained to the L-D cycle. The role of environmental lighting was further assessed in 14 animals exposed to constant light for 7 weeks. The results show that the basic rhythm was unchanged (mean period 3.18 +/- 0.06 h, peaks greater than 200 ng/ml, troughs less than 1 ng/ml), although entrainment to time of day was not evident. Subsequent exposure to the 12-h L-D cycle resulted in reversion to an entrained rhythm. These results suggest 1) that GH secretion in the rat is governed by an endogenous ultradian rhythm, with a periodicity of approximately 3.3 h, and 2) that the alternation of light and darkness probably serves as a Zeitgeber which sets the biological \"clock\" for GH secretion, but is not necessary for maintenance of the basic rhythm.", "contents": "Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Sequential blood samples were obtained from undisturbed freely-behaving male rats bearing chronic intracardiac venous cannulae. Blood was withdrawn every 15 min for periods of 4-24 h; plasma was separated, and saline-resuspended red cells were reinjected. Plasma GH was determined by radioimmunoassay. Pulsatile GH secretion was evident in each animal with most peak values greater than 200 ng/ml and most trough values less than ng/ml. The GH secretory episodes occurred at approximately 3 h intervals, and this rhythmic pattern of GH secretion persisted unchanged across all phases of a 12-h light-dark (L-D) cycle. Seven major episodes of GH secretion were observed during a single 24-h period. The mean period, or time interval between episodes, in 24 animals was 3.32 +/- 0.07 (SEM)h. The timing of the pulses with respect to the L-D cycle was similar in most animals, indicating that the rhythm may be entrained to the L-D cycle. The role of environmental lighting was further assessed in 14 animals exposed to constant light for 7 weeks. The results show that the basic rhythm was unchanged (mean period 3.18 +/- 0.06 h, peaks greater than 200 ng/ml, troughs less than 1 ng/ml), although entrainment to time of day was not evident. Subsequent exposure to the 12-h L-D cycle resulted in reversion to an entrained rhythm. These results suggest 1) that GH secretion in the rat is governed by an endogenous ultradian rhythm, with a periodicity of approximately 3.3 h, and 2) that the alternation of light and darkness probably serves as a Zeitgeber which sets the biological \"clock\" for GH secretion, but is not necessary for maintenance of the basic rhythm."} {"id": "PMID:1261488", "title": "Formation of 5alpha-reduced C19-steroids from progesterone in vitro by a pathway through 5alpha-reduced C21-steroids in ovaries of late prepubertal rats.", "content": "Ovarian homogenates from 10-150-day-old rats were incubated with [3H]progesterone and NADPH. Also, ovarian homogenates from 28-day-old rats were incubated for 5-180 min with either [14C]progesterone, [3H]5alpha-pregnane-3,20-dione or [14C]progesterone plus [3H]5alpha-pregnane-3,20-dione. Following incubation, radioactive metabolites were isolated, identified, and measured by column and paper chromatography, with derivative formation and recrystallizations to constant specific activity. Prepubertal ovaries (10, 20, and 28 days of age) converted 15-60% of progesterone to C21-17-hydroxysteroids and C19-steroids. At 40 and 150 days of age (postpubertal), the formation of these steroids decreased to less than 2%. At 10 and 150 days of age, the major C19-steroids formed from progesterone were androstenedione and testosterone. At 20 and 28 days of age, however, no accumulation of these C19-delta4-3ketosteroids was found (less than 0.1% of each), at which time the conversion of progesterone to 5alpha-reduced C19-steriods, such as androsterone and 5alpha-androstane-3alpha,17beta-diol, reached 30%. In ovaries of 28-day-old rats, the results from incubation studies for the detection of metabolic pathways indicated two biosynthetic pathways leading to 5alpha-reduced C19-steroids, one from progesterone via 5alpha-reduced C21 steroids, such as 3alpha-hydroxy-5alpha-pregnan-20-one and 3alpha,17alpha-dihydroxy-5alpha-pregnan-20-one, and a second via 17-hydroxyprogesterone, androstenedione, and testosterone. It seems that the active 5alpha-reduction of C19-delta4-3-ketosteroids and the formation of 5alpha-reduced C19-steroids by the pathway through 5alpha-reduced C21-steroids, are present in the ovaries of older prepubertal rats and may be the biological significance.", "contents": "Formation of 5alpha-reduced C19-steroids from progesterone in vitro by a pathway through 5alpha-reduced C21-steroids in ovaries of late prepubertal rats. Ovarian homogenates from 10-150-day-old rats were incubated with [3H]progesterone and NADPH. Also, ovarian homogenates from 28-day-old rats were incubated for 5-180 min with either [14C]progesterone, [3H]5alpha-pregnane-3,20-dione or [14C]progesterone plus [3H]5alpha-pregnane-3,20-dione. Following incubation, radioactive metabolites were isolated, identified, and measured by column and paper chromatography, with derivative formation and recrystallizations to constant specific activity. Prepubertal ovaries (10, 20, and 28 days of age) converted 15-60% of progesterone to C21-17-hydroxysteroids and C19-steroids. At 40 and 150 days of age (postpubertal), the formation of these steroids decreased to less than 2%. At 10 and 150 days of age, the major C19-steroids formed from progesterone were androstenedione and testosterone. At 20 and 28 days of age, however, no accumulation of these C19-delta4-3ketosteroids was found (less than 0.1% of each), at which time the conversion of progesterone to 5alpha-reduced C19-steriods, such as androsterone and 5alpha-androstane-3alpha,17beta-diol, reached 30%. In ovaries of 28-day-old rats, the results from incubation studies for the detection of metabolic pathways indicated two biosynthetic pathways leading to 5alpha-reduced C19-steroids, one from progesterone via 5alpha-reduced C21 steroids, such as 3alpha-hydroxy-5alpha-pregnan-20-one and 3alpha,17alpha-dihydroxy-5alpha-pregnan-20-one, and a second via 17-hydroxyprogesterone, androstenedione, and testosterone. It seems that the active 5alpha-reduction of C19-delta4-3-ketosteroids and the formation of 5alpha-reduced C19-steroids by the pathway through 5alpha-reduced C21-steroids, are present in the ovaries of older prepubertal rats and may be the biological significance."} {"id": "PMID:1261489", "title": "Effect of the ergot derivative lisuride hydrogen maleate on serum prolactin concentrations in female rats.", "content": "The influence of a new synthetic ergot derivative, lisuride hydrogen maleate (LHM) on serum prolactin (PRL) concentrations was investigated in female rats using different test models: 1. in reserpine (R)-pretreated intact females, and 2. in ovariectomized (OVX) estradiol benzoate (E2)-primed animals with or without an additional pretreatment with R. In all the models used LHM was strongly effective in lowering serum PRL. Doses from 0.025 to 0.5 mg/kg LHM, given orally as well as subcutaneously, suppressed serum PRL. Depending on the dose used, the serum PRL was lowered to a different extent for up to 12 h. LHM was at least as effective as the well-known potent inhibitor of PRL secretion CB-154 in lowering serum PRL in OVX rats primed with E2. The effects of R, E2, and LHM are described in relation to their mode of action within the hypothalamic-hypophyseal system which regulates PRL secretion. While the increase in serum PRL induced by R seems to be directly relatable to its known catecholamine depletion, the circadian rhythm of PRL secretion induced by E2 seems to be influenced or mediated by central neural mechanisms. The effects of LHM on serum PRL in these test models can be related to its dopaminergic action and constitute further evidence for the central functions of dopaminergic mechanisms in the regulation of PRL secretion.", "contents": "Effect of the ergot derivative lisuride hydrogen maleate on serum prolactin concentrations in female rats. The influence of a new synthetic ergot derivative, lisuride hydrogen maleate (LHM) on serum prolactin (PRL) concentrations was investigated in female rats using different test models: 1. in reserpine (R)-pretreated intact females, and 2. in ovariectomized (OVX) estradiol benzoate (E2)-primed animals with or without an additional pretreatment with R. In all the models used LHM was strongly effective in lowering serum PRL. Doses from 0.025 to 0.5 mg/kg LHM, given orally as well as subcutaneously, suppressed serum PRL. Depending on the dose used, the serum PRL was lowered to a different extent for up to 12 h. LHM was at least as effective as the well-known potent inhibitor of PRL secretion CB-154 in lowering serum PRL in OVX rats primed with E2. The effects of R, E2, and LHM are described in relation to their mode of action within the hypothalamic-hypophyseal system which regulates PRL secretion. While the increase in serum PRL induced by R seems to be directly relatable to its known catecholamine depletion, the circadian rhythm of PRL secretion induced by E2 seems to be influenced or mediated by central neural mechanisms. The effects of LHM on serum PRL in these test models can be related to its dopaminergic action and constitute further evidence for the central functions of dopaminergic mechanisms in the regulation of PRL secretion."} {"id": "PMID:1261490", "title": "Comparison of somatomedin activity in perfusates of normal and hypophysectomized rat livers with and without added growth hormone.", "content": "We compared the somatomedin (SM) activity of perfusates of livers from normal and hypophysectomized (hypox) rats with and without the addition of growth hormone (GH) to the perfusions. Livers were perfused for a total of 3 hours, with a change of Waymouth's medium MB 752/l every 30 min, in a continously recirculating system. SM activity was estimated by the stimulation of the incorporation of sulfate by hypox rat costal cartilage incubated in vitro. Endogenous SM activity (no addition of GH) in the perfusates of the livers of normal rats was initially 136 +/- 17% above buffer levels (mean +/- SE) and fell gradually to near-buffer levels over the first 2 1/2 hours. Endogenous SM activity in the perfusates of livers from hypox rats was initially 72 +/- 10% above buffer levels, significantly lower than that of the normal livers, and reached buffer levels with the fifth medium change. Pretreatment of hypox rats with GH in vivo increased their initial liver perfusate SM activity to 134 +/- 25%, comparable to that of normal livers and significantly greater than that of livers of untreated hypox rats. The addition of GH (25 mug/ml) to the perfusion of both normal and hypox rat livers led to significant increases in perfusate SM activity compared with that of control perfusates at the same time periods. The increase in SM activity was not significant until after 0-30 minutes with hypox livers, and after 30-90 minutes with normal livers. Although it has previously been reported that the direct addition of GH to livers perfusion systems led to an increase in perfusate SM activity, we have now established that in the absence of added GH, perfusates of normal rat livers contain significant SM activity, and that perfusates of normal rat livers contain more SM activity than perfusates of hypox rat livers. In addition, the observation that GH pretreatment increases the SM activity of perfusates of hypox rat livers constitutes the first evidence that SM activity of any body tissue may be altered by administration of GH in vivo.", "contents": "Comparison of somatomedin activity in perfusates of normal and hypophysectomized rat livers with and without added growth hormone. We compared the somatomedin (SM) activity of perfusates of livers from normal and hypophysectomized (hypox) rats with and without the addition of growth hormone (GH) to the perfusions. Livers were perfused for a total of 3 hours, with a change of Waymouth's medium MB 752/l every 30 min, in a continously recirculating system. SM activity was estimated by the stimulation of the incorporation of sulfate by hypox rat costal cartilage incubated in vitro. Endogenous SM activity (no addition of GH) in the perfusates of the livers of normal rats was initially 136 +/- 17% above buffer levels (mean +/- SE) and fell gradually to near-buffer levels over the first 2 1/2 hours. Endogenous SM activity in the perfusates of livers from hypox rats was initially 72 +/- 10% above buffer levels, significantly lower than that of the normal livers, and reached buffer levels with the fifth medium change. Pretreatment of hypox rats with GH in vivo increased their initial liver perfusate SM activity to 134 +/- 25%, comparable to that of normal livers and significantly greater than that of livers of untreated hypox rats. The addition of GH (25 mug/ml) to the perfusion of both normal and hypox rat livers led to significant increases in perfusate SM activity compared with that of control perfusates at the same time periods. The increase in SM activity was not significant until after 0-30 minutes with hypox livers, and after 30-90 minutes with normal livers. Although it has previously been reported that the direct addition of GH to livers perfusion systems led to an increase in perfusate SM activity, we have now established that in the absence of added GH, perfusates of normal rat livers contain significant SM activity, and that perfusates of normal rat livers contain more SM activity than perfusates of hypox rat livers. In addition, the observation that GH pretreatment increases the SM activity of perfusates of hypox rat livers constitutes the first evidence that SM activity of any body tissue may be altered by administration of GH in vivo."} {"id": "PMID:1261491", "title": "Antibodies to catecholamines.", "content": "The haptens p-tyramine and synephrine were conjugated to bovine serum albumin by means of the formaldehyde condensation reaction. These conjugates were emulsified in adjuvant and injected into rabbits. Antiserum was harvested at 10-day intervals after booster injections. The anti-sera were screened by immunodiffusion. After detecting the presence of antibody, an antiserum was further characterized by antiserum dilution curves, standard curves, and cross-reactivity studies using labeled p-tyramine or labeled metanephrine. The cross-reactivity studies indicated that the antisera to either hapten had low affinity to compounds with structural deviations on the side chain or ring other than at the position ortho to the phenolic hydroxyl group. The antisera were more sensitive to 3-methyoxylated compounds (3-methody-tyramine and metanephrine) than to 3-hydroxy or unsubstituted compounds.", "contents": "Antibodies to catecholamines. The haptens p-tyramine and synephrine were conjugated to bovine serum albumin by means of the formaldehyde condensation reaction. These conjugates were emulsified in adjuvant and injected into rabbits. Antiserum was harvested at 10-day intervals after booster injections. The anti-sera were screened by immunodiffusion. After detecting the presence of antibody, an antiserum was further characterized by antiserum dilution curves, standard curves, and cross-reactivity studies using labeled p-tyramine or labeled metanephrine. The cross-reactivity studies indicated that the antisera to either hapten had low affinity to compounds with structural deviations on the side chain or ring other than at the position ortho to the phenolic hydroxyl group. The antisera were more sensitive to 3-methyoxylated compounds (3-methody-tyramine and metanephrine) than to 3-hydroxy or unsubstituted compounds."} {"id": "PMID:1261492", "title": "Prepuberal estrogen treatment and somatic growth in rats.", "content": "Male and female rats receiving estradiol from weanling to early adulthood displayed a reduction in body weight gain and skeletal growth over the entire treatment period. At 76 days of age exogenous estrogen was discontinued and bilateral ovariectomies were performed on the females. The 17-week posthormone period was characterized by an accelerated rate of growth of both sexes; however, only the male rats had posthormone growth rates that indicated total compensation for the early depressant effects of estrogen. These results argue against recent proposals suggesting that mechanisms regulating the body weight and growth of rats are insensitive to estrogen until the onset of natural puberty. It is not clear from the present work what mechanism is responsible for the reduced growth. However, the similarities of the somatic growth effects of estradiol, as noted here, and the effects of undernutrition on young rats suggest that hypophagia may cause the depression of growth noted during estrogen treatment.", "contents": "Prepuberal estrogen treatment and somatic growth in rats. Male and female rats receiving estradiol from weanling to early adulthood displayed a reduction in body weight gain and skeletal growth over the entire treatment period. At 76 days of age exogenous estrogen was discontinued and bilateral ovariectomies were performed on the females. The 17-week posthormone period was characterized by an accelerated rate of growth of both sexes; however, only the male rats had posthormone growth rates that indicated total compensation for the early depressant effects of estrogen. These results argue against recent proposals suggesting that mechanisms regulating the body weight and growth of rats are insensitive to estrogen until the onset of natural puberty. It is not clear from the present work what mechanism is responsible for the reduced growth. However, the similarities of the somatic growth effects of estradiol, as noted here, and the effects of undernutrition on young rats suggest that hypophagia may cause the depression of growth noted during estrogen treatment."} {"id": "PMID:1261493", "title": "Comparison of the delayed actions of growth hormone and somatomedin on adipose tissue metabolism.", "content": "Although acute insulin-like effects of growth hormone (GH) on adipose tissue are readily demonstrable in vitro, it has not been possible to reproduce in vitro the delayed (3 h) inhibition of glucose utilization seen after the administration of GH in vivo. To examine the possibility that somatomedin (Sm), the postulated mediator of GH action, might, like GH, have biphasic effects on adipose tissue metabolism and mediate the delayed inhibition of glucose utilization, Sm was prepared by gel filtration from an acid-ethanol extract of normal rat plasma. The partially purified material increased 35SO4 incorporation into costal cartilage of hypophysectomized rats and produced in adipose tissue an acute stimulation of glucose oxidation that was not suppressed by insulin anti-serum. Unlike GH, whose insulin-like effects disappear in 3--4 hours, Sm-stimulated glucose oxidation remained linear for the entire 4 hour incubation period. Although acute stimulation of tissues with GH rendered them refractory to renewed insulin-like stimulation by GH, no such refractoriness to the action of Sm was seen. Furthermore, acute stimulation with Sm failed to render tissues refractory either to itself or to GH. Finally, Sm failed to reproduce the delayed lipolytic effects produced by GH in conjunction with glucocorticoids. These results make it highly unlikely that Sm alone accounts for the delayed metabolic effects of GH.", "contents": "Comparison of the delayed actions of growth hormone and somatomedin on adipose tissue metabolism. Although acute insulin-like effects of growth hormone (GH) on adipose tissue are readily demonstrable in vitro, it has not been possible to reproduce in vitro the delayed (3 h) inhibition of glucose utilization seen after the administration of GH in vivo. To examine the possibility that somatomedin (Sm), the postulated mediator of GH action, might, like GH, have biphasic effects on adipose tissue metabolism and mediate the delayed inhibition of glucose utilization, Sm was prepared by gel filtration from an acid-ethanol extract of normal rat plasma. The partially purified material increased 35SO4 incorporation into costal cartilage of hypophysectomized rats and produced in adipose tissue an acute stimulation of glucose oxidation that was not suppressed by insulin anti-serum. Unlike GH, whose insulin-like effects disappear in 3--4 hours, Sm-stimulated glucose oxidation remained linear for the entire 4 hour incubation period. Although acute stimulation of tissues with GH rendered them refractory to renewed insulin-like stimulation by GH, no such refractoriness to the action of Sm was seen. Furthermore, acute stimulation with Sm failed to render tissues refractory either to itself or to GH. Finally, Sm failed to reproduce the delayed lipolytic effects produced by GH in conjunction with glucocorticoids. These results make it highly unlikely that Sm alone accounts for the delayed metabolic effects of GH."} {"id": "PMID:1261494", "title": "Lack of effect of various endocrine manipulations on tryptophan hydroxylase activity of individual nuclei of the hypothalamus, limbic system, and midbrain of the rat.", "content": "The tryptophan hydroxylase activity of individual nuclei of the limbic system, hypothalamus, and midbrain was determined after various endocrine manipulations in an attempt to identify specific endocrine-responsive serotonergic structures in the rat brain. Following adrenalectomy, thyroidectomy, castration, or treatment with pharmacological doses of dexamethasone, testosterone, or thyroxine, no changes in tryptophan hydroxylase activity occurred in any of the areas of brain examined. Furthermore, in large sections of the hypothalamus and midbrain, total tryptophan hydroxylase activity was unaltered, and no changes in Km for substrate or co-factor were found after adrenalectomy. This study, therefore, has failed to detect any hormonally responsive tryptophan hydroxylase activity in the rat brain. These findings suggest that endocrine-induced alterations in serotonin turnover, if they occur, do so without measurable changes in the activity or kinetic properties of tryptophan hydroxylase.", "contents": "Lack of effect of various endocrine manipulations on tryptophan hydroxylase activity of individual nuclei of the hypothalamus, limbic system, and midbrain of the rat. The tryptophan hydroxylase activity of individual nuclei of the limbic system, hypothalamus, and midbrain was determined after various endocrine manipulations in an attempt to identify specific endocrine-responsive serotonergic structures in the rat brain. Following adrenalectomy, thyroidectomy, castration, or treatment with pharmacological doses of dexamethasone, testosterone, or thyroxine, no changes in tryptophan hydroxylase activity occurred in any of the areas of brain examined. Furthermore, in large sections of the hypothalamus and midbrain, total tryptophan hydroxylase activity was unaltered, and no changes in Km for substrate or co-factor were found after adrenalectomy. This study, therefore, has failed to detect any hormonally responsive tryptophan hydroxylase activity in the rat brain. These findings suggest that endocrine-induced alterations in serotonin turnover, if they occur, do so without measurable changes in the activity or kinetic properties of tryptophan hydroxylase."} {"id": "PMID:1261495", "title": "Mammary blood flow and endocrine changes during parturition in the ewe.", "content": "The temporal relationship between changes in mammary blood flow (MBF) and changes in the concentration of plasma prolactin, progesterone, estradiol-17beta, and cortisol, was examined in chronic sheep preparations undergoing spontaneous labor (Group I) or labor induced by an infusion of dexamethasone (1 mg/24 h) to the fetus (Group II). In Group I, an increase in prolactin (45 to 489 ng/ml), a decrease in progesterone (15 to 4 ng/ml), and an increase in MBF (97 to 365 ml/min) occurred at about the same time, whereas increases in estradiol-17beta (80 to 211 pg/ml) and cortisol (9 to 39 ng/ml) followed the change in MBF. A similar pattern of changes in MBF and hormonal concentrations occurred over a shorter period when premature labor was induced in the animals in Group II. These findings suggest that changes in plasma prolactin and progesterone concentrations play an important role in the regulation of MBF at the time of parturition.", "contents": "Mammary blood flow and endocrine changes during parturition in the ewe. The temporal relationship between changes in mammary blood flow (MBF) and changes in the concentration of plasma prolactin, progesterone, estradiol-17beta, and cortisol, was examined in chronic sheep preparations undergoing spontaneous labor (Group I) or labor induced by an infusion of dexamethasone (1 mg/24 h) to the fetus (Group II). In Group I, an increase in prolactin (45 to 489 ng/ml), a decrease in progesterone (15 to 4 ng/ml), and an increase in MBF (97 to 365 ml/min) occurred at about the same time, whereas increases in estradiol-17beta (80 to 211 pg/ml) and cortisol (9 to 39 ng/ml) followed the change in MBF. A similar pattern of changes in MBF and hormonal concentrations occurred over a shorter period when premature labor was induced in the animals in Group II. These findings suggest that changes in plasma prolactin and progesterone concentrations play an important role in the regulation of MBF at the time of parturition."} {"id": "PMID:1261496", "title": "Differential effects of L-thyroxine on cardiac and hepatic monoamine oxidase activity toward benzylamine and serotonin.", "content": "Male and female rats of 2 age groups were given subcutaneous injections of L-thyroxine (500 mug/kg) at 12 h intervals for a period of 10 days. The activity of monoamine oxidase (MAO) in normal and thyrotoxic rats was studied with two substrates: benzylamine and serotonin. The results showed that a thyroxine effect on cardiac and liver MAO activity is dependent on the substrate used in the assay. Kinetic studies of cardiac and liver MAO after thyroxine-treatment showed an unaltered Km for benzylamine but a change in Km for serotonin. Both findings may indicate a discriminative action of thyroid hormones on different forms of MAO. The possible presence of a soluble activator and inhibitor for MAO was investigated.", "contents": "Differential effects of L-thyroxine on cardiac and hepatic monoamine oxidase activity toward benzylamine and serotonin. Male and female rats of 2 age groups were given subcutaneous injections of L-thyroxine (500 mug/kg) at 12 h intervals for a period of 10 days. The activity of monoamine oxidase (MAO) in normal and thyrotoxic rats was studied with two substrates: benzylamine and serotonin. The results showed that a thyroxine effect on cardiac and liver MAO activity is dependent on the substrate used in the assay. Kinetic studies of cardiac and liver MAO after thyroxine-treatment showed an unaltered Km for benzylamine but a change in Km for serotonin. Both findings may indicate a discriminative action of thyroid hormones on different forms of MAO. The possible presence of a soluble activator and inhibitor for MAO was investigated."} {"id": "PMID:1261497", "title": "Isolation and characterization of follicle-stimulating hormone and luteinizing hormone and its subunits from snapping turtle (Chelydra serpentina) pituitaries.", "content": "Highly purified luteinizing hormone and follicle-stimulating hormone have been isolated from extracts of snapping turtle (Chelydra serpentina) pituitaries. Both hormones are potent in non-mammalian gonadotropin bioassays (1.8 X NIH-LH-S1 and 30 X NIH-FSH-S1). The materials have been characterized by polyacrylamide gel electrophoresis, amino terminal group analysis, amino acid and carbohydrate content, and, in the case of turtle luteinizing hormone, ultracentrifugation. The luteinizing hormone was shown to dissociate and subunits were prepared by the countercurrent distribution technique and characterized. Biological activity of the hormone could be regenerated by recombination of the subunits. In addition, it was shown that the snapping turtle luteinizing hormone subunits could be combined with subunits from ovine luteinizing hormone with generation of significant biological activity. Comparisons in properties of the turtle gonadotropins have been made with ovine gonadotropins, showing, in many cases, similarities in properties, suggesting structural features which have been conserved during evolution.", "contents": "Isolation and characterization of follicle-stimulating hormone and luteinizing hormone and its subunits from snapping turtle (Chelydra serpentina) pituitaries. Highly purified luteinizing hormone and follicle-stimulating hormone have been isolated from extracts of snapping turtle (Chelydra serpentina) pituitaries. Both hormones are potent in non-mammalian gonadotropin bioassays (1.8 X NIH-LH-S1 and 30 X NIH-FSH-S1). The materials have been characterized by polyacrylamide gel electrophoresis, amino terminal group analysis, amino acid and carbohydrate content, and, in the case of turtle luteinizing hormone, ultracentrifugation. The luteinizing hormone was shown to dissociate and subunits were prepared by the countercurrent distribution technique and characterized. Biological activity of the hormone could be regenerated by recombination of the subunits. In addition, it was shown that the snapping turtle luteinizing hormone subunits could be combined with subunits from ovine luteinizing hormone with generation of significant biological activity. Comparisons in properties of the turtle gonadotropins have been made with ovine gonadotropins, showing, in many cases, similarities in properties, suggesting structural features which have been conserved during evolution."} {"id": "PMID:1261498", "title": "Differentiation between neural and hormonal control of sexual behavior and gonadotropin secretion in the female rat.", "content": "The purpose of this study was to assess the relative roles of the neural and endocrine feed-back systems in the regulation of gonadotropin secretion and behavior in the female rat. Retrochiasmatic knife cuts were placed in animals which were tested for mating behavior on five consecutive days, subsequent to the development of cornified vaginal smears. A knife-cut control group was autopsied immediately after behavioral tests. A second knife-cut group and a group of cycling controls were acutely ovariectomized, and their behavior was assessed until mating ceased. Some of each of the two groups were administered small daily amounts of estradiol cypionate (estrogen) under two-dose regimens. Mating behavior and vaginal cytology were followed, and autopsies were performed 70 days after ovariectomy. At autopsy, serum was collected for LH, FSH, estradiol, and progesterone radioimmunoassays. The knife cuts caused high levels of mating on five consecutive days of testing in all animals. After ovariectomy, the surgical group mated at higher rates for longer time periods than did the controls, and the vaginal smears were predominately leukocytic. Knife cut controls had significantly elevated serum estrogen titers over cycling controls except for proestrous morning values. Exogenous estrogen was retained longer in the serum in the surgical than in the control group. Progesterone was relatively low in the retrochiasmatic cut groups. Serum LH was not elevated in the surgical groups except following ovariectomy; exogenous estrogen not only stimulated more mating sooner in the surgical group, but inhibited high levels of LH caused by ovariectomy. FSH was elevated in the surgical and control ovariectomized groups, and exogenous estrogen lowered FSH in the surgical but not the control group. Estrogen and LH levels were compared between the control and knife cut groups, and it was determined that the set-point for negative feedback effects of estrogen on LH was comparable for the two groups. It was concluded that retrochiasmatic knife cuts cause high estrogen titers, which may be responsible for the continuous behavior in animals with intact ovaries, whereas, in the absence of ovaries, the surgical treatment may reduce fore-brain inhibition on behavior. The data also suggest that the mediobasal hypothalamus in animals with retrochiasmatic knife cuts responds normally to exogenous estrogen by reducing LH secretion in the ovariectomized animal.", "contents": "Differentiation between neural and hormonal control of sexual behavior and gonadotropin secretion in the female rat. The purpose of this study was to assess the relative roles of the neural and endocrine feed-back systems in the regulation of gonadotropin secretion and behavior in the female rat. Retrochiasmatic knife cuts were placed in animals which were tested for mating behavior on five consecutive days, subsequent to the development of cornified vaginal smears. A knife-cut control group was autopsied immediately after behavioral tests. A second knife-cut group and a group of cycling controls were acutely ovariectomized, and their behavior was assessed until mating ceased. Some of each of the two groups were administered small daily amounts of estradiol cypionate (estrogen) under two-dose regimens. Mating behavior and vaginal cytology were followed, and autopsies were performed 70 days after ovariectomy. At autopsy, serum was collected for LH, FSH, estradiol, and progesterone radioimmunoassays. The knife cuts caused high levels of mating on five consecutive days of testing in all animals. After ovariectomy, the surgical group mated at higher rates for longer time periods than did the controls, and the vaginal smears were predominately leukocytic. Knife cut controls had significantly elevated serum estrogen titers over cycling controls except for proestrous morning values. Exogenous estrogen was retained longer in the serum in the surgical than in the control group. Progesterone was relatively low in the retrochiasmatic cut groups. Serum LH was not elevated in the surgical groups except following ovariectomy; exogenous estrogen not only stimulated more mating sooner in the surgical group, but inhibited high levels of LH caused by ovariectomy. FSH was elevated in the surgical and control ovariectomized groups, and exogenous estrogen lowered FSH in the surgical but not the control group. Estrogen and LH levels were compared between the control and knife cut groups, and it was determined that the set-point for negative feedback effects of estrogen on LH was comparable for the two groups. It was concluded that retrochiasmatic knife cuts cause high estrogen titers, which may be responsible for the continuous behavior in animals with intact ovaries, whereas, in the absence of ovaries, the surgical treatment may reduce fore-brain inhibition on behavior. The data also suggest that the mediobasal hypothalamus in animals with retrochiasmatic knife cuts responds normally to exogenous estrogen by reducing LH secretion in the ovariectomized animal."} {"id": "PMID:1261499", "title": "1,25-Dihydroxycholecalciferol effect on serum phosphorus homeostasis in rats.", "content": "It has recently been shown that 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) increases the serum phosphorus concentration of rats on a low-phosphorus diet. While studying the biological activity of 1,25(OH)2D3, we observed that under certain circumstances 1,25-(OH)2D3 would decrease the serum phosphorus concentration. The analysis of all data obtained in rat experiments during the past 3 years revealed highly significant linear correlations (P less than 0.001) between changes of serum phosphorus concentrations after the administration of 1,25-(OH)2-D3 (130 pmol/d for 1 or 5 days) and serum phosphorus or calcium levels in the animals before injection. Similar correlations could only be found with the higher dose of 25-hydroxycholecalciferol (130 pmol/d for 5 days). Another vitamin D3 metabolite, 24,25-dihydroxycholecalciferol, had no effect on serum phosphorus concentrations under our experimental conditions. The 1,25-(OH)2D3 effect on serum phosphorus concentration does not require the presence of circulating parathormone and/or calcitonin. We suggest that 1,25-(OH)2D3 might be an important factor in serum phosphorus homeostasis.", "contents": "1,25-Dihydroxycholecalciferol effect on serum phosphorus homeostasis in rats. It has recently been shown that 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) increases the serum phosphorus concentration of rats on a low-phosphorus diet. While studying the biological activity of 1,25(OH)2D3, we observed that under certain circumstances 1,25-(OH)2D3 would decrease the serum phosphorus concentration. The analysis of all data obtained in rat experiments during the past 3 years revealed highly significant linear correlations (P less than 0.001) between changes of serum phosphorus concentrations after the administration of 1,25-(OH)2-D3 (130 pmol/d for 1 or 5 days) and serum phosphorus or calcium levels in the animals before injection. Similar correlations could only be found with the higher dose of 25-hydroxycholecalciferol (130 pmol/d for 5 days). Another vitamin D3 metabolite, 24,25-dihydroxycholecalciferol, had no effect on serum phosphorus concentrations under our experimental conditions. The 1,25-(OH)2D3 effect on serum phosphorus concentration does not require the presence of circulating parathormone and/or calcitonin. We suggest that 1,25-(OH)2D3 might be an important factor in serum phosphorus homeostasis."} {"id": "PMID:1261500", "title": "Gap junctions in thyroid epithelium of the rat.", "content": "Gap junctions were observed on the lateral plasma membrane of the typical thyroid epithelial cell in freeze-fracture preparations of rat thyroid gland. The gap junctions were 0.1 to 0.4 mum in diameter and were composed of closely packed, approximately 80 nm particles. They were located from 1 to 6 mum from the apical surface of the cell.", "contents": "Gap junctions in thyroid epithelium of the rat. Gap junctions were observed on the lateral plasma membrane of the typical thyroid epithelial cell in freeze-fracture preparations of rat thyroid gland. The gap junctions were 0.1 to 0.4 mum in diameter and were composed of closely packed, approximately 80 nm particles. They were located from 1 to 6 mum from the apical surface of the cell."} {"id": "PMID:1261501", "title": "A granule-associated L-thyroxine deiodinating system in the human leukocyte.", "content": "Recent work has shown that leukocytes deiodinate L-thyroxine (T4) and that deiodination is enhanced when phagocytosis is induced. To define the subcellular locus and characteristics of this phenomenon, the deiodinative activities of different cell fractions obtained from human leukocytes (greater than 90% polymorphonuclear) were studied. Of the several fractions obtained, the granule fraction was found to possess the bulk of T4-deiodinative activity; as little as 9 mug/ml of granule protein effected significant deiodination of added labeled T4. Prior exposure of intact leukocytes to opsonized zymosan particles to induce phagocytosis resulted in an increase in the T4-deiodinative activity of the subsequently isolated granule fraction alone, strengthening the validity of the finding that T4-deiodinative activity in the human leukocyte resides in the granule fraction. The characteristics of the granule-associated deiodinating system suggest that it is enzymic in nature with a Km of the order of 10(-6)M.", "contents": "A granule-associated L-thyroxine deiodinating system in the human leukocyte. Recent work has shown that leukocytes deiodinate L-thyroxine (T4) and that deiodination is enhanced when phagocytosis is induced. To define the subcellular locus and characteristics of this phenomenon, the deiodinative activities of different cell fractions obtained from human leukocytes (greater than 90% polymorphonuclear) were studied. Of the several fractions obtained, the granule fraction was found to possess the bulk of T4-deiodinative activity; as little as 9 mug/ml of granule protein effected significant deiodination of added labeled T4. Prior exposure of intact leukocytes to opsonized zymosan particles to induce phagocytosis resulted in an increase in the T4-deiodinative activity of the subsequently isolated granule fraction alone, strengthening the validity of the finding that T4-deiodinative activity in the human leukocyte resides in the granule fraction. The characteristics of the granule-associated deiodinating system suggest that it is enzymic in nature with a Km of the order of 10(-6)M."} {"id": "PMID:1261502", "title": "Direct calcium-stimulated release of glucagon from the isolation perfused rat pancreas and the effect of chemical sympathectomy.", "content": "\"Staircase\" increments of calcium (from 0.5 to 15 mEq/L) were added to the perfused rat pancreas in the absence of glucagon secretogogues. Large spikes of glucagon release resulted, particularly at the small and large calcium concentrations. Insulin secretion was undetectable. Selective destruction of peripheral adrenergic neurons by pretreatment of the rats with 6-hydroxydopamine reduced the basal glucagon secretion to about 50% and specifically suppressed the calcium-induced glucagon release at the lower calcium steps. The response to a subsequent stimulation by arginine/calcium was not inhibited. Results suggest that glucagon secretion is modulated by a stimulant effect of the pancreatic adrenergic nerves (norepinephrine?) and that calcium in part positively affects release by permitting this neural stimulation.", "contents": "Direct calcium-stimulated release of glucagon from the isolation perfused rat pancreas and the effect of chemical sympathectomy. \"Staircase\" increments of calcium (from 0.5 to 15 mEq/L) were added to the perfused rat pancreas in the absence of glucagon secretogogues. Large spikes of glucagon release resulted, particularly at the small and large calcium concentrations. Insulin secretion was undetectable. Selective destruction of peripheral adrenergic neurons by pretreatment of the rats with 6-hydroxydopamine reduced the basal glucagon secretion to about 50% and specifically suppressed the calcium-induced glucagon release at the lower calcium steps. The response to a subsequent stimulation by arginine/calcium was not inhibited. Results suggest that glucagon secretion is modulated by a stimulant effect of the pancreatic adrenergic nerves (norepinephrine?) and that calcium in part positively affects release by permitting this neural stimulation."} {"id": "PMID:1261503", "title": "Effects of neurotensin and substance P on plasma insulin, glucagon and glucose levels.", "content": "Neurotensin and substance P given iv 5, 10, 20 and 30 minutes prior to blood collection produce hypoinsulinemia, hyperglucagonemia and hyperglycemia in the rat. Glucagon similarly produces hyperglycemia in rats but results in hyperinsulinemia. On a molar basis neurotensin is ca. 10 and 30 times more active in inducing hyperglycemia than substance P and glucagon, respectively. The enhanced glucogenic effects of neurotensin and substance P over glucagon may well result from their inhibition of insulin release. Neurotensin and substance P may be important in glucose homeostasis.", "contents": "Effects of neurotensin and substance P on plasma insulin, glucagon and glucose levels. Neurotensin and substance P given iv 5, 10, 20 and 30 minutes prior to blood collection produce hypoinsulinemia, hyperglucagonemia and hyperglycemia in the rat. Glucagon similarly produces hyperglycemia in rats but results in hyperinsulinemia. On a molar basis neurotensin is ca. 10 and 30 times more active in inducing hyperglycemia than substance P and glucagon, respectively. The enhanced glucogenic effects of neurotensin and substance P over glucagon may well result from their inhibition of insulin release. Neurotensin and substance P may be important in glucose homeostasis."} {"id": "PMID:1261504", "title": "Demonstration of specific binding of prolactin by porcine corpora lutea.", "content": "Subcellular fractions from porcine corpora lutea of the reproductive cycle and pregnancy were shown to have specific binding sites for ovine prolactin (oPRL). Aside from oPRL, only ovine and bovine growth hormone preparations competed with [125I]iodo-oPRL for its binding site. These cross reactions were at a level consistent with the prolactin contamination of these preparations. Rat growth hormone, FSH, LH, TSH, insulin, and ACTH exhibited negligible cross-reactivity. Both corpora hemorrhagica and albicantia had lower specific binding of [125I]iodoPRL than did active corpora lutea of the reproductive cycle, while corpora lutea of pregnancy demonstrated a nearly 5-fold increase in specific binding compared with that of the cycle. Corpora lutea from animals with larger fetuses (greater gestational age) bound the most prolactin. Analysis of data from cold competition studies employing weighted non-linear least-square fitting to a three-parameter model, showed high-affinity binding of oPRL with an association constant (Ka, 23 C) of 2.0 X 10(9)M-1 for the binding site of the corpus luteum of the cycle. The Ka shows no appreciable change with pregnancy. In contrast, the binding site concentration (N) increases markedly from less than 10 fmol/mg protein in corpora lutea from non-pregnant animals to approximately 40 fmol/mg protein for animals at a gestational stage of 40-46 days. The observed Ka's are similar to values obtained for the prolactin binding site in porcine granulosa cells harvested from unruptured follicles and to the prolactin-binding site in the mammary gland.", "contents": "Demonstration of specific binding of prolactin by porcine corpora lutea. Subcellular fractions from porcine corpora lutea of the reproductive cycle and pregnancy were shown to have specific binding sites for ovine prolactin (oPRL). Aside from oPRL, only ovine and bovine growth hormone preparations competed with [125I]iodo-oPRL for its binding site. These cross reactions were at a level consistent with the prolactin contamination of these preparations. Rat growth hormone, FSH, LH, TSH, insulin, and ACTH exhibited negligible cross-reactivity. Both corpora hemorrhagica and albicantia had lower specific binding of [125I]iodoPRL than did active corpora lutea of the reproductive cycle, while corpora lutea of pregnancy demonstrated a nearly 5-fold increase in specific binding compared with that of the cycle. Corpora lutea from animals with larger fetuses (greater gestational age) bound the most prolactin. Analysis of data from cold competition studies employing weighted non-linear least-square fitting to a three-parameter model, showed high-affinity binding of oPRL with an association constant (Ka, 23 C) of 2.0 X 10(9)M-1 for the binding site of the corpus luteum of the cycle. The Ka shows no appreciable change with pregnancy. In contrast, the binding site concentration (N) increases markedly from less than 10 fmol/mg protein in corpora lutea from non-pregnant animals to approximately 40 fmol/mg protein for animals at a gestational stage of 40-46 days. The observed Ka's are similar to values obtained for the prolactin binding site in porcine granulosa cells harvested from unruptured follicles and to the prolactin-binding site in the mammary gland."} {"id": "PMID:1261505", "title": "Differential effects of male stimuli on follicle-stimulating hormone, luteinizing hormone, and prolactin secretion in prepubertal female mice.", "content": "Puberty may be induced rapidly in young female mice by exposing them to adult males. The relevant male stimuli include a urinary pheromone and tactile cues, the latter acting in a potentiating capacity. The specific action of the urinary pheromone on pituitary gonadotropins was the subject of the present research. Immature females of a standard size were either paired with adult males, isolated and their bedding sprayed with male urine, or maintained as isolated controls. Exposure to male urine resulted in a rapid and significant release of LH (30 min) which was maintained at an average of 50% higher than levels in isolated controls throughout the 48 h experiment; no immediate changes were observed in either serum FSH or prolactin, but FSH was depressed and prolactin rose progressively during later sampling periods. Cohabitation with an adult male yielded parallel but decidedly stronger reponses in the concentrations of all three hormones. Exogenous estrogen, administered in a second experiment at a dosage previously found to mimic the puberty-inducing action of a male, suppressed serum FSH and LH while elevating serum prolactin. Thus, the present results suggest a) that the male's urinary stimulus exerts its action on immature females via LH release with no immediate and/or direct effects on the other two tropic hormones, and b) that the delayed alterations in serum FSH and prolactin concentrations accompanying male- and/or urine-exposure are secondary consequences of an LH-induced release of estradiol. Attempts to induce the entire pubertal cycle in intact females with subovulating doses of LH, nevertheless, were unsuccessful.", "contents": "Differential effects of male stimuli on follicle-stimulating hormone, luteinizing hormone, and prolactin secretion in prepubertal female mice. Puberty may be induced rapidly in young female mice by exposing them to adult males. The relevant male stimuli include a urinary pheromone and tactile cues, the latter acting in a potentiating capacity. The specific action of the urinary pheromone on pituitary gonadotropins was the subject of the present research. Immature females of a standard size were either paired with adult males, isolated and their bedding sprayed with male urine, or maintained as isolated controls. Exposure to male urine resulted in a rapid and significant release of LH (30 min) which was maintained at an average of 50% higher than levels in isolated controls throughout the 48 h experiment; no immediate changes were observed in either serum FSH or prolactin, but FSH was depressed and prolactin rose progressively during later sampling periods. Cohabitation with an adult male yielded parallel but decidedly stronger reponses in the concentrations of all three hormones. Exogenous estrogen, administered in a second experiment at a dosage previously found to mimic the puberty-inducing action of a male, suppressed serum FSH and LH while elevating serum prolactin. Thus, the present results suggest a) that the male's urinary stimulus exerts its action on immature females via LH release with no immediate and/or direct effects on the other two tropic hormones, and b) that the delayed alterations in serum FSH and prolactin concentrations accompanying male- and/or urine-exposure are secondary consequences of an LH-induced release of estradiol. Attempts to induce the entire pubertal cycle in intact females with subovulating doses of LH, nevertheless, were unsuccessful."} {"id": "PMID:1261506", "title": "Abnormal thyroid function in spontaneously hypertensive rats.", "content": "Thyroid weight, thyroidal radioiodide uptake, and cyclic AMP-dependent protein kinase activity of a thyroid supernatant fraction were increased significantly in spontaneously hypertensive rats (SHR), apparently because of increased secretion of pituitary TSH. However, the thyroids of SHR did not make supernormal amounts of thyroxine (T4), and thyroidal radioiodine release was apparently impaired. In the SHR, proteolytic enzyme activity was less than normal and the thyroglobulin was more resistant to normal proteolytic enzyme than was control thyroglobulin. Presumably because of these abnormalities, plasma T4 was significantly lower than normal, but triiodothyronine (T4) was normal, as a result of compensatory processes occurring in T3 synthesis and hydrolysis of thyroglobulin. T4 and T3 were less effective in depressing pituitary TSH synthesis and secretion in SHR than in controls, possibly because of an abnormal setting of the \"hormostat.\" Although the hypothalamic content of TRH was normal in SHR, the exact site of the abnormality in the \"hormostat\" is not delineated in the present study.", "contents": "Abnormal thyroid function in spontaneously hypertensive rats. Thyroid weight, thyroidal radioiodide uptake, and cyclic AMP-dependent protein kinase activity of a thyroid supernatant fraction were increased significantly in spontaneously hypertensive rats (SHR), apparently because of increased secretion of pituitary TSH. However, the thyroids of SHR did not make supernormal amounts of thyroxine (T4), and thyroidal radioiodine release was apparently impaired. In the SHR, proteolytic enzyme activity was less than normal and the thyroglobulin was more resistant to normal proteolytic enzyme than was control thyroglobulin. Presumably because of these abnormalities, plasma T4 was significantly lower than normal, but triiodothyronine (T4) was normal, as a result of compensatory processes occurring in T3 synthesis and hydrolysis of thyroglobulin. T4 and T3 were less effective in depressing pituitary TSH synthesis and secretion in SHR than in controls, possibly because of an abnormal setting of the \"hormostat.\" Although the hypothalamic content of TRH was normal in SHR, the exact site of the abnormality in the \"hormostat\" is not delineated in the present study."} {"id": "PMID:1261507", "title": "Growth hormone in encephalectomized rat fetuses, with comments on the effects of anesthetics.", "content": "Plasma and pituitary immunoreactive growth hormone (GH) was measured in 21.5-day-old rat fetuses under various experimental conditions. Encephalectomy on day 19.5 was used as a method for depriving the fetus of its hypothalamus. The fetuses were recovered on day 21.5 under maternal pentobarbital anesthesia. Total encephalectomy or partial encephalectomy (ablation of superficial brain structures) similarly affected fetal growth. The mean GH contents of the pituitaries were not significantly different in the four groups of fetuses studied: controls from intact females (1.38 +/- 0.19 mug/gland), controls from females submitted to surgery on day 19 (1.47 +/- 0.13 mug/gland), surgically encephalectomized fetuses (1.13 +/- 0.12 mug/gland), sham-operated fetuses (1.19 +/- 0.10 mug/gland). The mean plasma GH levels were the same in control fetuses of intact females (147 +/- 8 ng/ml) and in control fetuses of females submitted to surgery (168 +/- 9 ng/ml). The values were lower in sham-operated fetuses (118 +/- 11 ng/ml) and considerably reduced (P less than 0.001) in encephalectomized fetuses (60 +/- 8 ng/ml). Plasma GH was higher in the fetuses of females killed less than 2 min earlier, than in the fetuses of anesthetized females. In dams anesthetized with pentobarbital or ether, the fetal plasma levels of GH were not different after 15 or 45 min of maternal anesthesia. Under maternal urethane anesthesia, the fetal plasma GH was at 15 min significantly lower than it was under (P less than 0.01) or pentobarbital (P less than 0.05); 30 min later, it had increased by 40% (P less than 0.025). It appears that the release of GH in the fetus can be modified by anesthetics, and that some GH still is released by the pituitary gland in the absence of the hypothalamus.", "contents": "Growth hormone in encephalectomized rat fetuses, with comments on the effects of anesthetics. Plasma and pituitary immunoreactive growth hormone (GH) was measured in 21.5-day-old rat fetuses under various experimental conditions. Encephalectomy on day 19.5 was used as a method for depriving the fetus of its hypothalamus. The fetuses were recovered on day 21.5 under maternal pentobarbital anesthesia. Total encephalectomy or partial encephalectomy (ablation of superficial brain structures) similarly affected fetal growth. The mean GH contents of the pituitaries were not significantly different in the four groups of fetuses studied: controls from intact females (1.38 +/- 0.19 mug/gland), controls from females submitted to surgery on day 19 (1.47 +/- 0.13 mug/gland), surgically encephalectomized fetuses (1.13 +/- 0.12 mug/gland), sham-operated fetuses (1.19 +/- 0.10 mug/gland). The mean plasma GH levels were the same in control fetuses of intact females (147 +/- 8 ng/ml) and in control fetuses of females submitted to surgery (168 +/- 9 ng/ml). The values were lower in sham-operated fetuses (118 +/- 11 ng/ml) and considerably reduced (P less than 0.001) in encephalectomized fetuses (60 +/- 8 ng/ml). Plasma GH was higher in the fetuses of females killed less than 2 min earlier, than in the fetuses of anesthetized females. In dams anesthetized with pentobarbital or ether, the fetal plasma levels of GH were not different after 15 or 45 min of maternal anesthesia. Under maternal urethane anesthesia, the fetal plasma GH was at 15 min significantly lower than it was under (P less than 0.01) or pentobarbital (P less than 0.05); 30 min later, it had increased by 40% (P less than 0.025). It appears that the release of GH in the fetus can be modified by anesthetics, and that some GH still is released by the pituitary gland in the absence of the hypothalamus."} {"id": "PMID:1261508", "title": "Duodenal active transport of calcium and phosphate in vitamin D-deficient rats: effects of nephrectomy, Cestrum diurnum, and 1alpha,25-dihydroxyvitamin D3.", "content": "Both the methanol:chloroform extractable material from the leaves of the Solanaceous plant, Cestrum diurnum (C.d.), and a 270 ng dose of 1alpha, 25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) increased the active absorption of calcium and phosphate across the proximal duodenum, studied in vitro, from sham-operated and nephrectomized (NPX) vitamin D-deficient rats. In these studies, conducted 24 h after surgery, the uremic state in the NPX animals markedly diminished the intestinal transport response to 1alpha,25-(OH)2D3 and also lowered baseline transport values across duodenum from the NPX vitamin D-deficient controls. Both C.d. and 1alpha, 25-(OH)2D3 elevated plasma Ca levels equally well in the sham-operated and NPX groups. The stimulation of intestinal Ca absorption in NPX animals indicates that, like the leaves of the South American plant, Solanum glaucophyllum, C.d. contains materials which can function in an analogous manner to compounds in the vitamin D group that have either a 1alpha hydroxyl group or its steric equivalent.", "contents": "Duodenal active transport of calcium and phosphate in vitamin D-deficient rats: effects of nephrectomy, Cestrum diurnum, and 1alpha,25-dihydroxyvitamin D3. Both the methanol:chloroform extractable material from the leaves of the Solanaceous plant, Cestrum diurnum (C.d.), and a 270 ng dose of 1alpha, 25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) increased the active absorption of calcium and phosphate across the proximal duodenum, studied in vitro, from sham-operated and nephrectomized (NPX) vitamin D-deficient rats. In these studies, conducted 24 h after surgery, the uremic state in the NPX animals markedly diminished the intestinal transport response to 1alpha,25-(OH)2D3 and also lowered baseline transport values across duodenum from the NPX vitamin D-deficient controls. Both C.d. and 1alpha, 25-(OH)2D3 elevated plasma Ca levels equally well in the sham-operated and NPX groups. The stimulation of intestinal Ca absorption in NPX animals indicates that, like the leaves of the South American plant, Solanum glaucophyllum, C.d. contains materials which can function in an analogous manner to compounds in the vitamin D group that have either a 1alpha hydroxyl group or its steric equivalent."} {"id": "PMID:1261509", "title": "Prostaglandin-induced release of anterior pituitary hormones: structure-activity relationships.", "content": "Prostaglandins (PG's) of the E, F, A, or B series were infused into a lateral ventricle of the brain of adult male rats, and the efficacy of each PG to stimulate the discharge of LH, prolactin, and TSH from the pituitary gland was determined. PGE2, PGF2alpha, and PGF2beta were found to be potent stimulators of LH release. The release was considerably less when PGE1, PGF1beta, PGA2, or PGB2 was infused. The basal release of LH was not altered by infusion of PGF1alpha, PGA1, PGB1, or the control solution. It is suggested that the cis double bond in the 5,6 position and the 11-hydroxyl group are essential for the LH releasing activity of PG's and that these functional groups may be of importance for activation of a receptor at the level of the brain. Prolactin secretion was stimulated 6 to 7-fold by the infusion of 5 mug of PGE2, but 20 mug had no stimulatory effect. PGF2beta caused a 3 to 4-fold increase in basal plasma prolactin concentration and was the only PG tested other than PGE2 that stimulated prolactin release. None of the PG's infused intraventricularly affected TSH secretion.", "contents": "Prostaglandin-induced release of anterior pituitary hormones: structure-activity relationships. Prostaglandins (PG's) of the E, F, A, or B series were infused into a lateral ventricle of the brain of adult male rats, and the efficacy of each PG to stimulate the discharge of LH, prolactin, and TSH from the pituitary gland was determined. PGE2, PGF2alpha, and PGF2beta were found to be potent stimulators of LH release. The release was considerably less when PGE1, PGF1beta, PGA2, or PGB2 was infused. The basal release of LH was not altered by infusion of PGF1alpha, PGA1, PGB1, or the control solution. It is suggested that the cis double bond in the 5,6 position and the 11-hydroxyl group are essential for the LH releasing activity of PG's and that these functional groups may be of importance for activation of a receptor at the level of the brain. Prolactin secretion was stimulated 6 to 7-fold by the infusion of 5 mug of PGE2, but 20 mug had no stimulatory effect. PGF2beta caused a 3 to 4-fold increase in basal plasma prolactin concentration and was the only PG tested other than PGE2 that stimulated prolactin release. None of the PG's infused intraventricularly affected TSH secretion."} {"id": "PMID:1261510", "title": "Testosterone metabolism in rabbits actively immunized with testosterone.", "content": "Active immunization of male rabbits results in a marked increase in plasma testosterone (T) and in the fraction of T bound to circulating proteins. In order to identify the cause of the increased T levels, the half-life of T after castration, and the metabolic clearance rate (MCR) and production rate (PR) after a single injection of tritiated T were determined in normal and immunized rabbits. In the immunized animals the half-life of T was significantly longer, the MCR showed a 10-fold decrease (10.2 +/- 3.2 1/day compared to 108 +/- 43 1/day) and the PR was increased from 0.44 +/- 0.34 mg/day to 1.20 +/- 0.36 mg/day compared with the control group. The binding of T to circulating antibodies is considered to be the direct cause of the decreased MCR and, via the diminished negative feedback at the hypothalamic-pituitary levels, the indirect cause of the increased PR in the immunized animals.", "contents": "Testosterone metabolism in rabbits actively immunized with testosterone. Active immunization of male rabbits results in a marked increase in plasma testosterone (T) and in the fraction of T bound to circulating proteins. In order to identify the cause of the increased T levels, the half-life of T after castration, and the metabolic clearance rate (MCR) and production rate (PR) after a single injection of tritiated T were determined in normal and immunized rabbits. In the immunized animals the half-life of T was significantly longer, the MCR showed a 10-fold decrease (10.2 +/- 3.2 1/day compared to 108 +/- 43 1/day) and the PR was increased from 0.44 +/- 0.34 mg/day to 1.20 +/- 0.36 mg/day compared with the control group. The binding of T to circulating antibodies is considered to be the direct cause of the decreased MCR and, via the diminished negative feedback at the hypothalamic-pituitary levels, the indirect cause of the increased PR in the immunized animals."} {"id": "PMID:1261511", "title": "The effect of diabetes, insulin, and the redox potential on leucine metabolism by isolated rat hemidiaphragm.", "content": "The oxidation of leucine by hemidiaphragms of control and diabetic rats was studied in vitro. Rats were rendered diabetic with streptozotocin. Hemidiaphragms of diabetic rats produced approximately 50% more 14CO2 during incubation with 0.1 mM [1-14C]leucine than did control muscles. This was observed during incubation with or without glucose and in the presence or absence of a full complement of plasma amino acids. The concentration of leucine in the tissue water of hemidiaphragms from diabetic rats was greater than that in the control muscles before incubation. The specific activity of leucine at the end of 60 min incubation was not significantly different in diabetic and control muscles, indicating that the increased 14CO2 production represented stimulation of leucine oxidation. Hemidiaphragms of diabetic rats released more leucine into the medium during incubation than did control muscles. The stimulating effect of diabetes on leucine oxidation in vitro was reversible by insulin therapy prior to sacrifice. The addition of 5 mM pyruvate to a medium containing glucose inhibited 14CO2 production from [14C]leucine in control muscles, but stimulated leucine oxidation by hemidiaphragms of diabetic rats. Leucine oxidation by hemidiaphragms of diabetic rats was markedly stimulated by the addition of an electron acceptor, 0.02 mM methylene blue, suggesting that the NADH/NAD ratio may be rate-limiting for branched chain amino acid oxidation in muscles of diabetic rats, but not in muscles of controls. We suggest that the accelerated oxidation of branched chain amino acids by muscles may play a role in the acceleration of the muscle protein catabolism and gluconeogenesis which develop during insulin deficiency. The restraining effect of the cellular redox potential on branched chain amino acid oxidation may play a role in the eventual deceleration of protein catabolism during a prolonged fast.", "contents": "The effect of diabetes, insulin, and the redox potential on leucine metabolism by isolated rat hemidiaphragm. The oxidation of leucine by hemidiaphragms of control and diabetic rats was studied in vitro. Rats were rendered diabetic with streptozotocin. Hemidiaphragms of diabetic rats produced approximately 50% more 14CO2 during incubation with 0.1 mM [1-14C]leucine than did control muscles. This was observed during incubation with or without glucose and in the presence or absence of a full complement of plasma amino acids. The concentration of leucine in the tissue water of hemidiaphragms from diabetic rats was greater than that in the control muscles before incubation. The specific activity of leucine at the end of 60 min incubation was not significantly different in diabetic and control muscles, indicating that the increased 14CO2 production represented stimulation of leucine oxidation. Hemidiaphragms of diabetic rats released more leucine into the medium during incubation than did control muscles. The stimulating effect of diabetes on leucine oxidation in vitro was reversible by insulin therapy prior to sacrifice. The addition of 5 mM pyruvate to a medium containing glucose inhibited 14CO2 production from [14C]leucine in control muscles, but stimulated leucine oxidation by hemidiaphragms of diabetic rats. Leucine oxidation by hemidiaphragms of diabetic rats was markedly stimulated by the addition of an electron acceptor, 0.02 mM methylene blue, suggesting that the NADH/NAD ratio may be rate-limiting for branched chain amino acid oxidation in muscles of diabetic rats, but not in muscles of controls. We suggest that the accelerated oxidation of branched chain amino acids by muscles may play a role in the acceleration of the muscle protein catabolism and gluconeogenesis which develop during insulin deficiency. The restraining effect of the cellular redox potential on branched chain amino acid oxidation may play a role in the eventual deceleration of protein catabolism during a prolonged fast."} {"id": "PMID:1261512", "title": "The hypothalamic-neurohypophysial system of the rat: localization and quantitation of neurophysin by light microscopic immunocytochemistry in normal rats and in Brattleboro rats deficient in vasopressin and a neurophysin.", "content": "The cellular distribution of neurophysin was examined in hypothalami and neural lobes of normal Long-Evans rats and Brattleboro rats deficient in vasopressin and a major neurophysin. Tissue sections were treated with antisera to bovine, human, and rat neurophysins, using immunoperoxidase bridge techniques. Antisera to oxytocin (OT) and vasopressin (VP) were applied to adjacent sections. Two distinct cell populations were discernible in both magnocellular nuclei on the basis of the intensity of cytoplasmic staining. About half of the magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of homozygous Brattleboro rats with diabetes insipidus (DI) were devoid of immunoreactive neurophysin, OT, and VP. These cells were presumably the defective counterparts of those neurons that produce VP and its associated neurophysin in normal and heterozygous Brattleboro rats. The cells in homozygous DI rats which were stained with immunoreaction products to NP and OT were more concentrated in the dorsal part of the SON and in the periphery of the PVN. Spatial segregation of different neurons was also seen in the neural lobe, where clusters of stained axons were surrounded by bundles of nerve fibers lacking immunoreactive material. In normal rats and heterozygotes nearly all magnocellular neurons reacted immunologically with antiserum to neurophysin but with different intensities, so that \"dark\" and \"light\" cells could be distinguished. The darker cells in heterozygous Brattleboro rats had the same pattern of distribution as cells which contained OT. In homozygous DI rats, only some of those cells which contained neurophysin and OT exhibited a positive reaction with antiserum to VP due to slight reactivity with OT. The results obtained in the homozygous Brattleboro rat would suggest that OT and VP and their associated neurophysins are produced in different neurons in both the SON and PVN. However, in normal rats and in heterozygous Brattleboro rats, VP appeared to be present in both OT-positive and OT-negative neurons suggesting that some cells may have the capacity to synthesize two hormones.", "contents": "The hypothalamic-neurohypophysial system of the rat: localization and quantitation of neurophysin by light microscopic immunocytochemistry in normal rats and in Brattleboro rats deficient in vasopressin and a neurophysin. The cellular distribution of neurophysin was examined in hypothalami and neural lobes of normal Long-Evans rats and Brattleboro rats deficient in vasopressin and a major neurophysin. Tissue sections were treated with antisera to bovine, human, and rat neurophysins, using immunoperoxidase bridge techniques. Antisera to oxytocin (OT) and vasopressin (VP) were applied to adjacent sections. Two distinct cell populations were discernible in both magnocellular nuclei on the basis of the intensity of cytoplasmic staining. About half of the magnocellular neurons in the supraoptic (SON) and paraventricular (PVN) nuclei of homozygous Brattleboro rats with diabetes insipidus (DI) were devoid of immunoreactive neurophysin, OT, and VP. These cells were presumably the defective counterparts of those neurons that produce VP and its associated neurophysin in normal and heterozygous Brattleboro rats. The cells in homozygous DI rats which were stained with immunoreaction products to NP and OT were more concentrated in the dorsal part of the SON and in the periphery of the PVN. Spatial segregation of different neurons was also seen in the neural lobe, where clusters of stained axons were surrounded by bundles of nerve fibers lacking immunoreactive material. In normal rats and heterozygotes nearly all magnocellular neurons reacted immunologically with antiserum to neurophysin but with different intensities, so that \"dark\" and \"light\" cells could be distinguished. The darker cells in heterozygous Brattleboro rats had the same pattern of distribution as cells which contained OT. In homozygous DI rats, only some of those cells which contained neurophysin and OT exhibited a positive reaction with antiserum to VP due to slight reactivity with OT. The results obtained in the homozygous Brattleboro rat would suggest that OT and VP and their associated neurophysins are produced in different neurons in both the SON and PVN. However, in normal rats and in heterozygous Brattleboro rats, VP appeared to be present in both OT-positive and OT-negative neurons suggesting that some cells may have the capacity to synthesize two hormones."} {"id": "PMID:1261513", "title": "Relation between individual differences in sexual behavior and plasma testosterone levels in the guinea pig.", "content": "After 3 tests for male sex behavior, adult male guinea pigs were classified as either low-activity (LA, no ejaculations) or high-activity (HA, ejaculation during at least 2 behavior tests). In one experiment, resting levels of peripheral plasma testosterone (T), measured by radioimmunoassay, did not differ between the groups (LA=2.22 +/- 0.17 ng/ml, HA=2.09 +/- 0.11 ng/ml, X +/- SEM). However, plasma T levels were significantly higher in HA males 2 min after a sex test (2.27 +/- 0.24 ng/ml) than in LA males (1.40 +/- 0.20 ng/ml). A second experiment confirmed these results and also demonstrated that exposure of HA or LA males to an estrous female placed on the opposite side of a wire mesh barrier similarly led to higher T levels in HA than in LA males. These results indicate that a) behavioral differences between HA and LA guinea pigs are not attributable to differences in resting T levels, b) HA and LA males perceive the sex test situation differently, leading to slight increases in T in HA males and slight decreases in T in LA males, and c) these changes in T level are not dependent on copulation but can be induced by mere exposure to the sight smell and/or sound of an estrous female.", "contents": "Relation between individual differences in sexual behavior and plasma testosterone levels in the guinea pig. After 3 tests for male sex behavior, adult male guinea pigs were classified as either low-activity (LA, no ejaculations) or high-activity (HA, ejaculation during at least 2 behavior tests). In one experiment, resting levels of peripheral plasma testosterone (T), measured by radioimmunoassay, did not differ between the groups (LA=2.22 +/- 0.17 ng/ml, HA=2.09 +/- 0.11 ng/ml, X +/- SEM). However, plasma T levels were significantly higher in HA males 2 min after a sex test (2.27 +/- 0.24 ng/ml) than in LA males (1.40 +/- 0.20 ng/ml). A second experiment confirmed these results and also demonstrated that exposure of HA or LA males to an estrous female placed on the opposite side of a wire mesh barrier similarly led to higher T levels in HA than in LA males. These results indicate that a) behavioral differences between HA and LA guinea pigs are not attributable to differences in resting T levels, b) HA and LA males perceive the sex test situation differently, leading to slight increases in T in HA males and slight decreases in T in LA males, and c) these changes in T level are not dependent on copulation but can be induced by mere exposure to the sight smell and/or sound of an estrous female."} {"id": "PMID:1261514", "title": "The effects of insulin and growth hormone on the release of somatomedin by the isolated rat liver.", "content": "Livers from hypophysectomized (hypox) rats were perfused with oxygenated Waymouth's medium in a system which permitted continuous recirculation for separate 30 minute periods after which fresh medium was supplied. In most experiments 6 changes of medium were carried out over a 3 hour period. The somatomedin activity of each perfusate was determined by measuring its ability to stimulate sulfate uptake in hypox rat cartilage in vitro. For comparison between experiments the results are expressed as the per cent stimulation of sulfate uptake by the perfusate compared with the unperfused buffer. Without hormonal additions there was a progressive fall in the release of somatomedin activity during the 6 periods of study. When compared with the results without hormone, the addition of 1000 muU/ml of insulin per ml of medium during the 2nd to 6th period led to a significant increase in perfusate somatomedin activity at all periods. The addition of 100 muU/ml of insulin was without significant effect. The possible inter-relationship between insulin and growth hormone in the regulation of somatomedin release was studied with a dose of bGH of 250 ng/ml which had previously been shown to be insufficient by itsel to stimulate somatomedin release. When added to a medium containing 1000 muU/ml of insulin, this dose of bGH did not significantly stimulate somatomedin release beyond that obtained with insulin alone. However, when 250 ng/ml was added to a medium containing 100 muU/ml insulin, a significant stimulation of somatomedin release was observed while the addition of each hormone separately was without significant effect. These results support the hypothesis that insulin shares with GH the regulation of somatomedin release by the liver. Differences in insulin concentration may explain some clinical situations in which somatomedin concentrations cannot be correlated with GH levels.", "contents": "The effects of insulin and growth hormone on the release of somatomedin by the isolated rat liver. Livers from hypophysectomized (hypox) rats were perfused with oxygenated Waymouth's medium in a system which permitted continuous recirculation for separate 30 minute periods after which fresh medium was supplied. In most experiments 6 changes of medium were carried out over a 3 hour period. The somatomedin activity of each perfusate was determined by measuring its ability to stimulate sulfate uptake in hypox rat cartilage in vitro. For comparison between experiments the results are expressed as the per cent stimulation of sulfate uptake by the perfusate compared with the unperfused buffer. Without hormonal additions there was a progressive fall in the release of somatomedin activity during the 6 periods of study. When compared with the results without hormone, the addition of 1000 muU/ml of insulin per ml of medium during the 2nd to 6th period led to a significant increase in perfusate somatomedin activity at all periods. The addition of 100 muU/ml of insulin was without significant effect. The possible inter-relationship between insulin and growth hormone in the regulation of somatomedin release was studied with a dose of bGH of 250 ng/ml which had previously been shown to be insufficient by itsel to stimulate somatomedin release. When added to a medium containing 1000 muU/ml of insulin, this dose of bGH did not significantly stimulate somatomedin release beyond that obtained with insulin alone. However, when 250 ng/ml was added to a medium containing 100 muU/ml insulin, a significant stimulation of somatomedin release was observed while the addition of each hormone separately was without significant effect. These results support the hypothesis that insulin shares with GH the regulation of somatomedin release by the liver. Differences in insulin concentration may explain some clinical situations in which somatomedin concentrations cannot be correlated with GH levels."} {"id": "PMID:1261515", "title": "The cell-free synthesis of the alpha subunit of human chorionic gonadotropin.", "content": "The synthesis of the alpha subunit of human chorionic gonadotropin (hCG) was demonstrated in a cell-free system composed of polysomes derived from first trimester placenta and cell sap prepared from ascites tumor cells. The in vitro synthesized proteins labeled with [35S]methionine were shown to have at least 4 tryptic peptides that co-migrated with the same peptides from authentic hCG. Sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed the synthesis of a discrete protein, migrating with an apparent molecular weight of about 17,000, which contained methionine-labeled tryptic peptides found in the alpha subunit. The level of radioactivity in these tryptic peptides was five times greater with polysomes from first trimester placentae than with those from term placentae. The efficiency of total protein synthesis in both cases was about the same. These data strongly suggest that the decrease in blood levels of hCG after the first trimester is caused by a selective decrease in the rate of synthesis of the hormone.", "contents": "The cell-free synthesis of the alpha subunit of human chorionic gonadotropin. The synthesis of the alpha subunit of human chorionic gonadotropin (hCG) was demonstrated in a cell-free system composed of polysomes derived from first trimester placenta and cell sap prepared from ascites tumor cells. The in vitro synthesized proteins labeled with [35S]methionine were shown to have at least 4 tryptic peptides that co-migrated with the same peptides from authentic hCG. Sodium dodecylsulfate-polyacrylamide gel electrophoresis revealed the synthesis of a discrete protein, migrating with an apparent molecular weight of about 17,000, which contained methionine-labeled tryptic peptides found in the alpha subunit. The level of radioactivity in these tryptic peptides was five times greater with polysomes from first trimester placentae than with those from term placentae. The efficiency of total protein synthesis in both cases was about the same. These data strongly suggest that the decrease in blood levels of hCG after the first trimester is caused by a selective decrease in the rate of synthesis of the hormone."} {"id": "PMID:1261516", "title": "Effect of hysterectomy on serum luteinizing hormone concentrations and on corpus luteum function in the rat.", "content": "Serum progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were estimated in intact and hysterectomized pseudopregnant rats. Progesterone concentrations increased significantly from day 2 of pseudopregnancy (PSP) onwards, and a plateau was reached on days 4 and 5. No significant differences in progesterone concentrations between intact and long-term hysterectomized animals were observed until day 10 of PSP. In the intact rats, progesterone concentrations decreased after day 8, but in the hysterectomized rats they remained elevated until days 18-20 of PSP. No differences between FSH concentrations in intact and hysterectomized rats were found. In hysterectomized rats, however, LH concentrations were significantly lower than those in the intact rats on days 2-7 of PSP. When hysterectomy was performed on day 2 of PSP (acute hysterectomy) lower LH concentrations were also found in the hysterectomized animals compared with sham-operated animals. No differences in progesterone concentrations were found between sham-operated controls and acutely hysterectomized animals on days 3-8 of PSP. It was found that LH concentrations in ovariectomized long-term hysterectomized rats were lower than those in ovariectomized, but otherwise intact, animals. In contrast to its effect on tonic LH secretion, long-term hysterectomy had no influence on the surge of LH during the afternoon of proestrus. In both intact and long-term hysterectomized rats the duration of PSP was not significantly altered after transplantation of an ovary under the kidney capsule and the removal of the ovaries in situ. It is concluded that hysterectomy leads to a decreased LH secretion by the pituitary gland, but has no influence on the maximal progesterone concentrations during PSP. The significance of these findings, particularly with regard to the prolongation of PSP after hysterectomy, is discussed.", "contents": "Effect of hysterectomy on serum luteinizing hormone concentrations and on corpus luteum function in the rat. Serum progesterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations were estimated in intact and hysterectomized pseudopregnant rats. Progesterone concentrations increased significantly from day 2 of pseudopregnancy (PSP) onwards, and a plateau was reached on days 4 and 5. No significant differences in progesterone concentrations between intact and long-term hysterectomized animals were observed until day 10 of PSP. In the intact rats, progesterone concentrations decreased after day 8, but in the hysterectomized rats they remained elevated until days 18-20 of PSP. No differences between FSH concentrations in intact and hysterectomized rats were found. In hysterectomized rats, however, LH concentrations were significantly lower than those in the intact rats on days 2-7 of PSP. When hysterectomy was performed on day 2 of PSP (acute hysterectomy) lower LH concentrations were also found in the hysterectomized animals compared with sham-operated animals. No differences in progesterone concentrations were found between sham-operated controls and acutely hysterectomized animals on days 3-8 of PSP. It was found that LH concentrations in ovariectomized long-term hysterectomized rats were lower than those in ovariectomized, but otherwise intact, animals. In contrast to its effect on tonic LH secretion, long-term hysterectomy had no influence on the surge of LH during the afternoon of proestrus. In both intact and long-term hysterectomized rats the duration of PSP was not significantly altered after transplantation of an ovary under the kidney capsule and the removal of the ovaries in situ. It is concluded that hysterectomy leads to a decreased LH secretion by the pituitary gland, but has no influence on the maximal progesterone concentrations during PSP. The significance of these findings, particularly with regard to the prolongation of PSP after hysterectomy, is discussed."} {"id": "PMID:1261517", "title": "Thyroid hormone metabolism during liver regeneration in rats.", "content": "The metabolism of thyroid hormones was studied during the prereplicative period of liver regeneration. After partial hepatectomy, serum thyroxine (T4) and triiodothyronine (T3) levles progressively fell, and reached a nadir at 12 h proportional to the quantity of liver tissue exised. The diminution (60-80%) in serum iodothyronines was related specifically to partial hepatectomy because laparotomy, ether anesthesia, and other stressful surgical procedures did not induce similar changes. At least 3 phenomena appear to be involved: 1) increased utilization and turnover of thyroid hormone by the regenerating liver remmant. 2) diminished hormone secretion by the thyroid gland between 6-12 h after surgery, and 3) a slightly reduced concentration of serum iodothyronine carrier proteins. The results support the concept that the liver participates in the metabolic regulation of T2 and T4 which in turn, control hepatocellular growth. It is suggested, however, that additional unknown factors control increased hepatic thyroid hormone turnover after partial hepatectomy.", "contents": "Thyroid hormone metabolism during liver regeneration in rats. The metabolism of thyroid hormones was studied during the prereplicative period of liver regeneration. After partial hepatectomy, serum thyroxine (T4) and triiodothyronine (T3) levles progressively fell, and reached a nadir at 12 h proportional to the quantity of liver tissue exised. The diminution (60-80%) in serum iodothyronines was related specifically to partial hepatectomy because laparotomy, ether anesthesia, and other stressful surgical procedures did not induce similar changes. At least 3 phenomena appear to be involved: 1) increased utilization and turnover of thyroid hormone by the regenerating liver remmant. 2) diminished hormone secretion by the thyroid gland between 6-12 h after surgery, and 3) a slightly reduced concentration of serum iodothyronine carrier proteins. The results support the concept that the liver participates in the metabolic regulation of T2 and T4 which in turn, control hepatocellular growth. It is suggested, however, that additional unknown factors control increased hepatic thyroid hormone turnover after partial hepatectomy."} {"id": "PMID:1261518", "title": "Electron microscope immunohistochemical localization of thyroglobulin in the rat thyroid gland.", "content": "In order to make a precise identification of the organelles containing thyroglobulin (TG) in the thyroid follicular cells, an electron microscope immunohistochemical localization of TG was conducted in the rat thyroid gland. In both control and TSH-treated rats, TG was detected in the follicular lumen, in large vesicles which correspond to the classical colloid droplets, in apical vesicles, and also in the apical cytoplasm. When the formation of colloid droplets was prevented by the previous administration of L-thyroxine, a positive reaction for TG was observed only in the colloid and apical vesicles, and diffusely in the cytoplasm. These results clearly establish for the first time the presence of immunoreactive TG in apical vesicles, luminal colloid and colloid droplets, and cytoplasm (possibly cell sap). They confirm previous indirect evidence suggesting that apical vesicles are involved in the transport of TG and that colloid droplets whose formation is induced by TSH, do contain TG.", "contents": "Electron microscope immunohistochemical localization of thyroglobulin in the rat thyroid gland. In order to make a precise identification of the organelles containing thyroglobulin (TG) in the thyroid follicular cells, an electron microscope immunohistochemical localization of TG was conducted in the rat thyroid gland. In both control and TSH-treated rats, TG was detected in the follicular lumen, in large vesicles which correspond to the classical colloid droplets, in apical vesicles, and also in the apical cytoplasm. When the formation of colloid droplets was prevented by the previous administration of L-thyroxine, a positive reaction for TG was observed only in the colloid and apical vesicles, and diffusely in the cytoplasm. These results clearly establish for the first time the presence of immunoreactive TG in apical vesicles, luminal colloid and colloid droplets, and cytoplasm (possibly cell sap). They confirm previous indirect evidence suggesting that apical vesicles are involved in the transport of TG and that colloid droplets whose formation is induced by TSH, do contain TG."} {"id": "PMID:1261519", "title": "Control of cell growth. IV. Growth properties of a new cell line established from an estrogen-dependent kidney tumor of the Syrian hamster.", "content": "A permanent cell line has been established in culture from an estrogen-dependent kidney tumor of the Syrian hamster. The cells were selected from mixed populations by three methods: 1) animal passage enrichment, 2) growth on petri dishes, and 3) serum-type dependence. The inoculation of these cells, designated the H-301 line, into host animals showed tumor formation in estrogen-treated males or estrogen-treated females, but no tumor formation in normal or castrated hamsters of either sex. The estrogen-dependent tumor formation in male hamsters by H-301 cells was inhibited by progesterone, hydrocortisone, and testosterone. When H-301 cell growth was examined in culture, the addition of estrogens or other steroid hormones to the medium over the range of 0.1 to 10 ng/ml showed no growth-stimulating or inhibiting effects. Medium prepared with charcoal-extracted serum (to reduce by 90% the endogenous levels of steroid hormones) supported growth as well as medium prepared with normal serum. Furthermore, the addition of either estrogens, testosterone, or antiestrogens to medium prepared with charcoal-extracted serum showed no significant effects upon growth. We have shown also that culture medium prepared with serum from young calves did not support the growth of the cells, and the addition of estrogens to this medium did not change this growth pattern. However, the addition of fetal calf serum to medium already containing calf serum promoted maximal growth. Evidence is presented that the growth-promoting agent in fetal calf serum was inactivated by a 90 C heat treatment. Furthermore, the ether-soluble fractions from fetal calf serum and horse serum did not significantly improve growth when added to calf serum containing medium. We conclude that estrogens or other steroid hormones alone are not sufficient to promote the growth of the H-301 cells, but that heat-labile serum factors are required.", "contents": "Control of cell growth. IV. Growth properties of a new cell line established from an estrogen-dependent kidney tumor of the Syrian hamster. A permanent cell line has been established in culture from an estrogen-dependent kidney tumor of the Syrian hamster. The cells were selected from mixed populations by three methods: 1) animal passage enrichment, 2) growth on petri dishes, and 3) serum-type dependence. The inoculation of these cells, designated the H-301 line, into host animals showed tumor formation in estrogen-treated males or estrogen-treated females, but no tumor formation in normal or castrated hamsters of either sex. The estrogen-dependent tumor formation in male hamsters by H-301 cells was inhibited by progesterone, hydrocortisone, and testosterone. When H-301 cell growth was examined in culture, the addition of estrogens or other steroid hormones to the medium over the range of 0.1 to 10 ng/ml showed no growth-stimulating or inhibiting effects. Medium prepared with charcoal-extracted serum (to reduce by 90% the endogenous levels of steroid hormones) supported growth as well as medium prepared with normal serum. Furthermore, the addition of either estrogens, testosterone, or antiestrogens to medium prepared with charcoal-extracted serum showed no significant effects upon growth. We have shown also that culture medium prepared with serum from young calves did not support the growth of the cells, and the addition of estrogens to this medium did not change this growth pattern. However, the addition of fetal calf serum to medium already containing calf serum promoted maximal growth. Evidence is presented that the growth-promoting agent in fetal calf serum was inactivated by a 90 C heat treatment. Furthermore, the ether-soluble fractions from fetal calf serum and horse serum did not significantly improve growth when added to calf serum containing medium. We conclude that estrogens or other steroid hormones alone are not sufficient to promote the growth of the H-301 cells, but that heat-labile serum factors are required."} {"id": "PMID:1261520", "title": "Ontogeny of sensitivity to growth hormone in rat diaphragm muscle.", "content": "In order to delineate the ages of onset and decline in sensitivity to growth hormone (GH) in rats, the ability of ovine GH in vitro to stimulate amino acid uptake and protein synthesis was studied in diaphragm muscle. GH (25 mug/ml) produced a significant, but small (12-17%), stimulation of alpha-aminoisobutyric acid (AIB, 1 mM) uptake in diaphragms from fed intact rats 7-24 days old, but not from 21-day fetuses or from fed rats 4, 30, 50, 100, or 130 days old. When intact rats were fasted for 24 h, both the magnitude and consistency of the responses to GH increased considerably. In fasted rats, GH significantly stimulated AIB transport by 10,29, 77,111, and 58% at ages 4, 7, 11, 15, and 23 days, respectively; GH was not effective at age 3 or 30 days. At age 15 days, 0.5 mug/ml GH stimulated AIB transport by 96%. GH (25 or 0.5 mug/ml) significantly increased leucine incorporation into protein at age 15 days in fasted intact rats. When rats were hypophysectomized at age 28, 47, or 98 days and tested 2-3 days later, the basal rate of protein synthesis fell, but the basal rate of AIB transport did not; however, GH now stimulated both AIB uptake and amino acid incorporation into protein. These results suggest that rat diaphragm muscle first becomes sensitive to GH at about age 4-7 days (AIB transport), but that further development may be necessary for the anabolic action of the hormone (protein synthesis) to be seen. Stimulation of AIB uptake is maximal about 15 days after birth. Thereafter, diaphragm muscles from normal rats becomes progressively more refractory to the acute stimulatory effects of GH on transport processes. Hypphysectomy of rats 30 days old or more leads to the re-establishment of GH-responsiveness by the AIB transport system. This cannot be attributed merely to a lowering of the basal transport rate; rather hypophysectomy appears to result in the loss of an inhibitor of growth hormone's acute stimulatory actions on transport processes. Previous work suggests that this refractory state is produced in normal rats by occasional surges of endogenous growth hormone. The dominance of the refractory state appears about the time of weaning. This may protect the weaned rat, whose diet is more variable than it is during the suckling period, from periodic depletion of amino acids and glucose from the plasma in response to intermittent surges of GH, thereby allowing GH to produce a sustained stimulation of protein synthesis and growth.", "contents": "Ontogeny of sensitivity to growth hormone in rat diaphragm muscle. In order to delineate the ages of onset and decline in sensitivity to growth hormone (GH) in rats, the ability of ovine GH in vitro to stimulate amino acid uptake and protein synthesis was studied in diaphragm muscle. GH (25 mug/ml) produced a significant, but small (12-17%), stimulation of alpha-aminoisobutyric acid (AIB, 1 mM) uptake in diaphragms from fed intact rats 7-24 days old, but not from 21-day fetuses or from fed rats 4, 30, 50, 100, or 130 days old. When intact rats were fasted for 24 h, both the magnitude and consistency of the responses to GH increased considerably. In fasted rats, GH significantly stimulated AIB transport by 10,29, 77,111, and 58% at ages 4, 7, 11, 15, and 23 days, respectively; GH was not effective at age 3 or 30 days. At age 15 days, 0.5 mug/ml GH stimulated AIB transport by 96%. GH (25 or 0.5 mug/ml) significantly increased leucine incorporation into protein at age 15 days in fasted intact rats. When rats were hypophysectomized at age 28, 47, or 98 days and tested 2-3 days later, the basal rate of protein synthesis fell, but the basal rate of AIB transport did not; however, GH now stimulated both AIB uptake and amino acid incorporation into protein. These results suggest that rat diaphragm muscle first becomes sensitive to GH at about age 4-7 days (AIB transport), but that further development may be necessary for the anabolic action of the hormone (protein synthesis) to be seen. Stimulation of AIB uptake is maximal about 15 days after birth. Thereafter, diaphragm muscles from normal rats becomes progressively more refractory to the acute stimulatory effects of GH on transport processes. Hypphysectomy of rats 30 days old or more leads to the re-establishment of GH-responsiveness by the AIB transport system. This cannot be attributed merely to a lowering of the basal transport rate; rather hypophysectomy appears to result in the loss of an inhibitor of growth hormone's acute stimulatory actions on transport processes. Previous work suggests that this refractory state is produced in normal rats by occasional surges of endogenous growth hormone. The dominance of the refractory state appears about the time of weaning. This may protect the weaned rat, whose diet is more variable than it is during the suckling period, from periodic depletion of amino acids and glucose from the plasma in response to intermittent surges of GH, thereby allowing GH to produce a sustained stimulation of protein synthesis and growth."} {"id": "PMID:1261521", "title": "Calcitonin secretion in vitro. II. Regulatory effects of enteric mammalian polypeptide hormones on trout C-cell cultures.", "content": "We have studied the effects of several porcine enteric polypeptide hormones on trout calcitonin (tCT) secretion in long-lived monolayer cultures of calcitonin-secreting (C-) cells derived from trout ultimobranchial glands. Gastrin, pancreozymin (CCK-PZ), glucagon, and secretin have dose-related stimulatory effects on tCT secretion; the distinct effects of secretin on tCT secretion are in contrast to its lack of CT secretagogue activity in some mammals. Synthetic peptide hormones and/or their structural analogs have variable secretory effects which correspond in general to the potency of the analogs for the well-recognized biological actions of these various peptide hormones in mammals. Although enteric peptide hormones are present in fish, their physiological role in the regulation of CT secretion has not been studied. These in vitro studies indicate a possible role for these hormones in the control of tCT secretion and support the concept that there are differences in the regulators of C-cell function in higher and lower vertebrates. In vitro studies of fish CT secretion are needed to establish the physiological significance of these in vitro studies of fish C-cell function.", "contents": "Calcitonin secretion in vitro. II. Regulatory effects of enteric mammalian polypeptide hormones on trout C-cell cultures. We have studied the effects of several porcine enteric polypeptide hormones on trout calcitonin (tCT) secretion in long-lived monolayer cultures of calcitonin-secreting (C-) cells derived from trout ultimobranchial glands. Gastrin, pancreozymin (CCK-PZ), glucagon, and secretin have dose-related stimulatory effects on tCT secretion; the distinct effects of secretin on tCT secretion are in contrast to its lack of CT secretagogue activity in some mammals. Synthetic peptide hormones and/or their structural analogs have variable secretory effects which correspond in general to the potency of the analogs for the well-recognized biological actions of these various peptide hormones in mammals. Although enteric peptide hormones are present in fish, their physiological role in the regulation of CT secretion has not been studied. These in vitro studies indicate a possible role for these hormones in the control of tCT secretion and support the concept that there are differences in the regulators of C-cell function in higher and lower vertebrates. In vitro studies of fish CT secretion are needed to establish the physiological significance of these in vitro studies of fish C-cell function."} {"id": "PMID:1261522", "title": "The effect of growth hormone on parathyroid function in rats.", "content": "The effect of excessive growth hormone (GH) on parathyroid function in rats was evaluated in order to determine whether the GH-induced increase in serum calcium (Ca) may be mediated via stimulation of parathyroid hormone (PTH) secretion. Rats receiving injections of bovine GH 2 mg daily for 4 weeks showed a progressive significant increase in both serum Ca and immunoreactive PTH (iPTH) after the second week. Rats receiving daily injections of rat GH, 0.25 mg daily for 3 weeks, followed by 0.5 mg daily for 3 additional weeks, showed a significant increase in serum iPTH during administration of the higher dose, and also a significantly increased parathyroid gland weight and PTH content. The concomitant increase in serum Ca and iPTH suggest that GH stimulates the parathyroid glands to increase PTH secretion, which in turn causes an increase in serum Ca. The parathyroid response increases with the increase in dose and duration of GH stimulus. The data suggest that the hypercalcemia often observed in acromegaly may be due, at least in part, to GH-induced excessive secretory activity of the parathyroid glands.", "contents": "The effect of growth hormone on parathyroid function in rats. The effect of excessive growth hormone (GH) on parathyroid function in rats was evaluated in order to determine whether the GH-induced increase in serum calcium (Ca) may be mediated via stimulation of parathyroid hormone (PTH) secretion. Rats receiving injections of bovine GH 2 mg daily for 4 weeks showed a progressive significant increase in both serum Ca and immunoreactive PTH (iPTH) after the second week. Rats receiving daily injections of rat GH, 0.25 mg daily for 3 weeks, followed by 0.5 mg daily for 3 additional weeks, showed a significant increase in serum iPTH during administration of the higher dose, and also a significantly increased parathyroid gland weight and PTH content. The concomitant increase in serum Ca and iPTH suggest that GH stimulates the parathyroid glands to increase PTH secretion, which in turn causes an increase in serum Ca. The parathyroid response increases with the increase in dose and duration of GH stimulus. The data suggest that the hypercalcemia often observed in acromegaly may be due, at least in part, to GH-induced excessive secretory activity of the parathyroid glands."} {"id": "PMID:1261523", "title": "Comparative effectiveness of preoptic and tuberal stimulation for luteinizing hormone release and ovulation in two strains of rats.", "content": "Proestrous rats under pentobarbital anesthesia during the 'critical period' were electrically stimulated in either the medial preoptic area (mPOA) or the anterior basal tuber. In Osborne-Mendel (O-M) and Charles River CD rats, comparisons were made of the ovulatory responses to trains of matched biphasic pulse pairs of different microamperage, 30 sec on and 30 sec off for 45 min. In CD rats, comparisons were made of the relative efficiencies of stimulation through a coaxial platinum electrode near the midline and a pair of platinum electrodes spaced bilaterally 2 mm apart across either the mPOA or the tuber. Other comparisons, with either type of electrode in the basal tuber, were made between 4-day and 5-day cyclic CD rats with respect both to the ovulatory responses and to the serum concentrations of LH 90 min after the start of the 45-min stimulus. In both O-M and CD rats, tuberal stimulation was more effective for ovulation than mPOA stimulation. CD rats were much less responsive to mPOA stimulation (spaced electrodes) than O-M rats, but the responses of both strains to tuberal stimulation were essentially alike. In 4-day cyclic CD rats, the ovulatory responses to mPOA stimulation with the coaxial electrode were much superior to those from spaced-electrode stimulation. In contrast, tuberal stimulation with either type of electrode gave equivalent ovulation frequencies and equivalent tubal ovum numbers in both 4-day and 5-day cyclic rats. However, the serum LH concentrations disclosed somewhat better responses to stimulation with the coaxial electrode (coaxial/spaced=1.57). The advantage of stimulation with the coaxial electrode may be due to high current density or, at least in part, to its more medial location. The results are compatible with the concept of preoptic-tuberal neuronal system, diffuse rostrally and convergent upon the medial basal tuber, controlling the ovulatory surge of LH.", "contents": "Comparative effectiveness of preoptic and tuberal stimulation for luteinizing hormone release and ovulation in two strains of rats. Proestrous rats under pentobarbital anesthesia during the 'critical period' were electrically stimulated in either the medial preoptic area (mPOA) or the anterior basal tuber. In Osborne-Mendel (O-M) and Charles River CD rats, comparisons were made of the ovulatory responses to trains of matched biphasic pulse pairs of different microamperage, 30 sec on and 30 sec off for 45 min. In CD rats, comparisons were made of the relative efficiencies of stimulation through a coaxial platinum electrode near the midline and a pair of platinum electrodes spaced bilaterally 2 mm apart across either the mPOA or the tuber. Other comparisons, with either type of electrode in the basal tuber, were made between 4-day and 5-day cyclic CD rats with respect both to the ovulatory responses and to the serum concentrations of LH 90 min after the start of the 45-min stimulus. In both O-M and CD rats, tuberal stimulation was more effective for ovulation than mPOA stimulation. CD rats were much less responsive to mPOA stimulation (spaced electrodes) than O-M rats, but the responses of both strains to tuberal stimulation were essentially alike. In 4-day cyclic CD rats, the ovulatory responses to mPOA stimulation with the coaxial electrode were much superior to those from spaced-electrode stimulation. In contrast, tuberal stimulation with either type of electrode gave equivalent ovulation frequencies and equivalent tubal ovum numbers in both 4-day and 5-day cyclic rats. However, the serum LH concentrations disclosed somewhat better responses to stimulation with the coaxial electrode (coaxial/spaced=1.57). The advantage of stimulation with the coaxial electrode may be due to high current density or, at least in part, to its more medial location. The results are compatible with the concept of preoptic-tuberal neuronal system, diffuse rostrally and convergent upon the medial basal tuber, controlling the ovulatory surge of LH."} {"id": "PMID:1261524", "title": "Exaggeration of experimental hypertension in rats by contraceptive steroids (Enovid).", "content": "The possibly additive pressor effects of contraceptive steroids were studied by treating hypertensive rats chronically with Enovid. Renal hypertensive rats were unaffected by drug treatment during the first 5 weeks, but, from the 6th to the 8th week, Enovid-treated rats had much higher systolic pressures than those given corn oil alone. However, these differences dwindled and became insignificant from the 9th to the 16th week despite continued treatment. Subsequently, other rats were pretreated with Enovid or corn oil for 5 weeks before hypertension was induced by implanting deoxycorticosterone acetate (Doca). In contrast to the equivocal results obtained previously, Doca hypertension was consistently more pronounced in rats treated with Enovid than in those given corn oil. This pressure difference was later verified by direct measurement of phasic aortic pressures from indwelling catheters and by the postmortem finding that Enovid-treated rats had larger hearts than corn oil-treated ones. The exact mechanism by which Enovid enhances Doca hypertension is still undetermined, but sympathetic hyperactivity was considered an unlikely explanation, since responses to posterior hypothalamic stimulation, norepinephrine, or ganglion blockade with pentolinium were unaltered.", "contents": "Exaggeration of experimental hypertension in rats by contraceptive steroids (Enovid). The possibly additive pressor effects of contraceptive steroids were studied by treating hypertensive rats chronically with Enovid. Renal hypertensive rats were unaffected by drug treatment during the first 5 weeks, but, from the 6th to the 8th week, Enovid-treated rats had much higher systolic pressures than those given corn oil alone. However, these differences dwindled and became insignificant from the 9th to the 16th week despite continued treatment. Subsequently, other rats were pretreated with Enovid or corn oil for 5 weeks before hypertension was induced by implanting deoxycorticosterone acetate (Doca). In contrast to the equivocal results obtained previously, Doca hypertension was consistently more pronounced in rats treated with Enovid than in those given corn oil. This pressure difference was later verified by direct measurement of phasic aortic pressures from indwelling catheters and by the postmortem finding that Enovid-treated rats had larger hearts than corn oil-treated ones. The exact mechanism by which Enovid enhances Doca hypertension is still undetermined, but sympathetic hyperactivity was considered an unlikely explanation, since responses to posterior hypothalamic stimulation, norepinephrine, or ganglion blockade with pentolinium were unaltered."} {"id": "PMID:1261525", "title": "Thyroidal iodine metabolism during the development of the chick embryo.", "content": "Stable iodine was measured in the thyroid gland of the chick embryo from day 9 to day 20 of incubation in order to evaluate quantitatively the functional development of the gland. Total iodine content increased progressively during incubation. From day 9 to day 17 of incubation, this increase resulted from the increases of pellet-bound iodine and of soluble iodine. Afterwards, it essentially paralleled the increase of the soluble thyroglobulin-bound iodine which reflected the increase in both thyroglobulin content and the degree of iodination of the thyroglobulin. The total iodine, thyroglobulin-bound iodine and thyroglobulin (TG) content, increased as power functions of time during incubation, with critical times on days 11 and 15. Their concentrations also increased during the whole incubation period, while the iodide concentration remained roughly constant (25 ng/mg) from day 13 to day 19. Only one iodoprotein, 19.5 S TG, was found, and its heterogeneity of iodination was demonstrated during the whole period of incubation studied (from day 11 to day 20). The degree of dissociation with sodium dodecyl sulfate (SDS) of the TG into 12 S subunits decreased as the degree of iodination of the TG increased. Throughout embryonic development, iodine was bound more and more to TG molecules, which were resistant to dissociation with SDS. While the average iodine content of the TG increased, no appreciable changes were found in iodotyrosine and iodothyronine percentages of TG-bound iodine: monoiodotyrosine, 26%; diiodotyrosine, 43%; thyroxine 12%; 3,5,3'-triiodothyronine, 2.5%. As a consequence, a linear relationship existed for each iodoamino acid between the number of its residues per mole of TG and the iodine content of TG (127I atoms per mole)-- about 30 atoms of iodine was required to form 1 mole of T4. The low efficiency of the TG of the chick embryo as a thyroidal hormone-forming protein was compensated for by its high degree of iodination.", "contents": "Thyroidal iodine metabolism during the development of the chick embryo. Stable iodine was measured in the thyroid gland of the chick embryo from day 9 to day 20 of incubation in order to evaluate quantitatively the functional development of the gland. Total iodine content increased progressively during incubation. From day 9 to day 17 of incubation, this increase resulted from the increases of pellet-bound iodine and of soluble iodine. Afterwards, it essentially paralleled the increase of the soluble thyroglobulin-bound iodine which reflected the increase in both thyroglobulin content and the degree of iodination of the thyroglobulin. The total iodine, thyroglobulin-bound iodine and thyroglobulin (TG) content, increased as power functions of time during incubation, with critical times on days 11 and 15. Their concentrations also increased during the whole incubation period, while the iodide concentration remained roughly constant (25 ng/mg) from day 13 to day 19. Only one iodoprotein, 19.5 S TG, was found, and its heterogeneity of iodination was demonstrated during the whole period of incubation studied (from day 11 to day 20). The degree of dissociation with sodium dodecyl sulfate (SDS) of the TG into 12 S subunits decreased as the degree of iodination of the TG increased. Throughout embryonic development, iodine was bound more and more to TG molecules, which were resistant to dissociation with SDS. While the average iodine content of the TG increased, no appreciable changes were found in iodotyrosine and iodothyronine percentages of TG-bound iodine: monoiodotyrosine, 26%; diiodotyrosine, 43%; thyroxine 12%; 3,5,3'-triiodothyronine, 2.5%. As a consequence, a linear relationship existed for each iodoamino acid between the number of its residues per mole of TG and the iodine content of TG (127I atoms per mole)-- about 30 atoms of iodine was required to form 1 mole of T4. The low efficiency of the TG of the chick embryo as a thyroidal hormone-forming protein was compensated for by its high degree of iodination."} {"id": "PMID:1261527", "title": "Characterization of acid phosphatase isoenzymes in human skin fibroblasts.", "content": "The multiple acid phosphatase isoenzymes of cultivated skin fibroblasts were investigated in an effort to further clarify the basis of the observed molecular heterogeneity. Treatment with neuraminidase did not alter the migration of isoenzymes present prior to treatment with neuraminidase did not alter the migration of isoenzymes present prior to treatment, but additional isoenzymes were detectable after treatment. Variation of enzymes, permitting prediction of net charge and molecular size differences. Isoelectric focusing between pH 5.0 and pH 8.0 demonstrated three isoenzymes of acid phosphatase in the total cell homogenate and in the lysosomal fraction, two of which appeared to have similar isoelectric points.", "contents": "Characterization of acid phosphatase isoenzymes in human skin fibroblasts. The multiple acid phosphatase isoenzymes of cultivated skin fibroblasts were investigated in an effort to further clarify the basis of the observed molecular heterogeneity. Treatment with neuraminidase did not alter the migration of isoenzymes present prior to treatment with neuraminidase did not alter the migration of isoenzymes present prior to treatment, but additional isoenzymes were detectable after treatment. Variation of enzymes, permitting prediction of net charge and molecular size differences. Isoelectric focusing between pH 5.0 and pH 8.0 demonstrated three isoenzymes of acid phosphatase in the total cell homogenate and in the lysosomal fraction, two of which appeared to have similar isoelectric points."} {"id": "PMID:1261528", "title": "Response of plasma and red cell glutathione reductase of several mammalian species and domestic chickens to flavin adenine dinucleotide.", "content": "Glutathione reductase (GR) activity was determined in the plasma and red cells from a number of species (human, horse, cattle, sheep, chicken, rabbit, rat). The species with the highest plasma activity (horse and cattle) had the lowest red cell activity. Unlike red cell GR, plasma GR was not significantly stimulated by the addition of flavin adenine dinucleotide (FAD). In species with high plasma GR activity the determination of whole blood FAD activity coefficients may not be a good index of riboflavin status.", "contents": "Response of plasma and red cell glutathione reductase of several mammalian species and domestic chickens to flavin adenine dinucleotide. Glutathione reductase (GR) activity was determined in the plasma and red cells from a number of species (human, horse, cattle, sheep, chicken, rabbit, rat). The species with the highest plasma activity (horse and cattle) had the lowest red cell activity. Unlike red cell GR, plasma GR was not significantly stimulated by the addition of flavin adenine dinucleotide (FAD). In species with high plasma GR activity the determination of whole blood FAD activity coefficients may not be a good index of riboflavin status."} {"id": "PMID:1261529", "title": "Ultrasonic measurement of arterial blood pressure in conditioned thoroughbreds.", "content": "Indirect systolic and diastolic arterial pressure measurements of 456 Thoroughbred horses of various ages and sex stabled at 9 different race tracks were measured with an ultrasonic-Doppler device interfaced with a sphygmomanometer cuff. The mean systolic pressure was 111.8 +/- 13.3 mmHg and the mean diastolic pressure was 69.6 +/- 13.8 mmHg in this population.", "contents": "Ultrasonic measurement of arterial blood pressure in conditioned thoroughbreds. Indirect systolic and diastolic arterial pressure measurements of 456 Thoroughbred horses of various ages and sex stabled at 9 different race tracks were measured with an ultrasonic-Doppler device interfaced with a sphygmomanometer cuff. The mean systolic pressure was 111.8 +/- 13.3 mmHg and the mean diastolic pressure was 69.6 +/- 13.8 mmHg in this population."} {"id": "PMID:1261530", "title": "The current position of A.I. in horse breeding.", "content": "This short review article describes the various techniques currently available for artificial insemination in the horse. The collection and use of raw and extended semen is discussed together with the more recent developments in freezing semen. The expected conception rates with both fresh and frozen semen are quoted. The possible benefits in disease control and stud management are discussed, as well as the difficulties in controlling the use of A.I. from the Breed Registration Authorities point of view.", "contents": "The current position of A.I. in horse breeding. This short review article describes the various techniques currently available for artificial insemination in the horse. The collection and use of raw and extended semen is discussed together with the more recent developments in freezing semen. The expected conception rates with both fresh and frozen semen are quoted. The possible benefits in disease control and stud management are discussed, as well as the difficulties in controlling the use of A.I. from the Breed Registration Authorities point of view."} {"id": "PMID:1261531", "title": "A case of peritoneal mesothelioma in a thoroughbred mare.", "content": "The report describes a case of abdominal neoplasia in a mare diagnosed ante-mortem by the technique of paracentesis abdominis. Histopathological findings suggest that the lesion was a mesothelioma, primarily involving the greater omentum.", "contents": "A case of peritoneal mesothelioma in a thoroughbred mare. The report describes a case of abdominal neoplasia in a mare diagnosed ante-mortem by the technique of paracentesis abdominis. Histopathological findings suggest that the lesion was a mesothelioma, primarily involving the greater omentum."} {"id": "PMID:1261532", "title": "Cytology of diffuse mesothelioma in the thorax of a horse.", "content": "Examination of effusions from body cavities must include a search for neoplastic as well as inflammatory cells. Neoplastic cells found in the thorax are generally derived from adenocarcinomas or mesotheliomas. Mesotheliomas are relatively uncommon and the neoplastic cells found in effusions are difficult to differentiate from activated cells in inflammatory effusions. An ante-mortem diagnosis of mesothelioma was made in a mare on the basis of the large volume of fluid produced, the pleomorphic mesothelial cells, the polyp formation and the absence of PAS staining material after digestion of the cell impression with maltase diastase.", "contents": "Cytology of diffuse mesothelioma in the thorax of a horse. Examination of effusions from body cavities must include a search for neoplastic as well as inflammatory cells. Neoplastic cells found in the thorax are generally derived from adenocarcinomas or mesotheliomas. Mesotheliomas are relatively uncommon and the neoplastic cells found in effusions are difficult to differentiate from activated cells in inflammatory effusions. An ante-mortem diagnosis of mesothelioma was made in a mare on the basis of the large volume of fluid produced, the pleomorphic mesothelial cells, the polyp formation and the absence of PAS staining material after digestion of the cell impression with maltase diastase."} {"id": "PMID:1261533", "title": "A preliminary study of the measurement of plasma osmotic pressure in equine medicine.", "content": "The normal plasma osmotic pressure was established in 205 Thoroughbred horses. Samples taken from horses suffering from a variety of diseases showed that measurement of this parameter might prove a valuable non specific test for assessing the severity of some diseases in which there are alterations in metabolism.", "contents": "A preliminary study of the measurement of plasma osmotic pressure in equine medicine. The normal plasma osmotic pressure was established in 205 Thoroughbred horses. Samples taken from horses suffering from a variety of diseases showed that measurement of this parameter might prove a valuable non specific test for assessing the severity of some diseases in which there are alterations in metabolism."} {"id": "PMID:1261534", "title": "Therapy of a horse with diarrhoea of unknown aetiology.", "content": "A 5 year old Thoroughbred stallion with diarrhoea of unknown aetiology was referred to Davis. Treatment was aimed at terminating diarrhoea and restoring normal fluid status. Laboratory aids were utilised to establish where inbalance and deficits were present. Antibiotics and corticosteroids were used as an adjunct to fluid therapy. The case history and rationale of treatment of fluid disorders resulting from diarrhoea are discussed.", "contents": "Therapy of a horse with diarrhoea of unknown aetiology. A 5 year old Thoroughbred stallion with diarrhoea of unknown aetiology was referred to Davis. Treatment was aimed at terminating diarrhoea and restoring normal fluid status. Laboratory aids were utilised to establish where inbalance and deficits were present. Antibiotics and corticosteroids were used as an adjunct to fluid therapy. The case history and rationale of treatment of fluid disorders resulting from diarrhoea are discussed."} {"id": "PMID:1261535", "title": "Studies of new intracellular proteases in various organs of rats. Participation of proteases in degradation of ornithine aminotransferase in vitro and in vivo.", "content": "Homogenates of the muscle layer of rat small intestine irreversibly inactivated endogenous ornithine aminotransferase at 37 degrees C. Addition to the homogenate of coenzymes and the various keto-acids which act as substrate inhibited conversion of the holoenzyme to the apoenzyme and its subsequent degradation. Addition of protease inhibitors including soybean trypsin inhibitor, chymostatin and phenylmethylsulfonyl fluoride almost completely prevented inactivation of he enzyme. Immunological activity decreased during inactivation of the enzyme, but its rate of decrease was much slower than that of loss of enzyme activity. Antigen-antibody precipitates from homogenates containing inactivated enzyme, were separated by electrophoresis on sodium dodecylsulfate-polyacrylamide gels. In this way breakdown products of the enzyme were found, indicating that the enzyme in homogenates was inactivated by limited proteolysis. These results obtained in vitro support our previous suggestion (1975) of a stepwise mechanism for degradation of pyridoxal enzymes.", "contents": "Studies of new intracellular proteases in various organs of rats. Participation of proteases in degradation of ornithine aminotransferase in vitro and in vivo. Homogenates of the muscle layer of rat small intestine irreversibly inactivated endogenous ornithine aminotransferase at 37 degrees C. Addition to the homogenate of coenzymes and the various keto-acids which act as substrate inhibited conversion of the holoenzyme to the apoenzyme and its subsequent degradation. Addition of protease inhibitors including soybean trypsin inhibitor, chymostatin and phenylmethylsulfonyl fluoride almost completely prevented inactivation of he enzyme. Immunological activity decreased during inactivation of the enzyme, but its rate of decrease was much slower than that of loss of enzyme activity. Antigen-antibody precipitates from homogenates containing inactivated enzyme, were separated by electrophoresis on sodium dodecylsulfate-polyacrylamide gels. In this way breakdown products of the enzyme were found, indicating that the enzyme in homogenates was inactivated by limited proteolysis. These results obtained in vitro support our previous suggestion (1975) of a stepwise mechanism for degradation of pyridoxal enzymes."} {"id": "PMID:1261536", "title": "Characterization and replication control of plasmids from Enterobacter cloacae DF 13.", "content": "It has been shown previously that Enterobacter clocacae DF13 harbours at least five different size classes of plasmids. A 45 x 10(6)-Mr self-transmissible R factor determining resistance against tetracyclin, sulfanilamide, streptomycin and chloramphenicol, a 6.0 x 10(6)-Mr bacteriocinogenic factor without sex factors activity and cryptic plasmids in the size classes of Mr 1.3 x10(6), 2.8 x 10(6) and 8.0 x 10(6) respectively. The present work deals with the determination of the homogeneity and molecular relationship of 1.3 x 10(6)-Mr (mini) and 2.8 x 10(6)-Mr (midi) cryptic plasmids and the 6.0 x 10(6)-Mr (maxi) bacteriocinogenic factor, their kinetics of replication and their replication control in response to inhibition of protein synthesis.", "contents": "Characterization and replication control of plasmids from Enterobacter cloacae DF 13. It has been shown previously that Enterobacter clocacae DF13 harbours at least five different size classes of plasmids. A 45 x 10(6)-Mr self-transmissible R factor determining resistance against tetracyclin, sulfanilamide, streptomycin and chloramphenicol, a 6.0 x 10(6)-Mr bacteriocinogenic factor without sex factors activity and cryptic plasmids in the size classes of Mr 1.3 x10(6), 2.8 x 10(6) and 8.0 x 10(6) respectively. The present work deals with the determination of the homogeneity and molecular relationship of 1.3 x 10(6)-Mr (mini) and 2.8 x 10(6)-Mr (midi) cryptic plasmids and the 6.0 x 10(6)-Mr (maxi) bacteriocinogenic factor, their kinetics of replication and their replication control in response to inhibition of protein synthesis."} {"id": "PMID:1261537", "title": "The involvement of RNA in the initiation of DNA synthesis in mammalian cells. Artifacts arising during caesium-salt density-gradient centrifugation which simulate a covalent attachment of RNA to newly synthesized DNA.", "content": "Artifacts were encountered during caesium salt density gradient centrifugation which simulated results expected if newly synthesized DNA is covalently attached to RNA. Newly synthesized DNA (in baby hamster kidney cells, BHK-21/C13), pulse-labelled with [3H]thymidine for 10 min at temperatures below 25 degrees C, banded at a greater buoyant density than mature [14C]DNA (heat-denatured nucleic acids) when centrifuged to equilibrium in caesium chloride gradients. Some of the newly synthesized RNA, labelled with [3H]uridine, banded at a buoyant density slightly greater than DNA in caesium sulphate gradients. These results were not obtained when nucleic acids were pulse-labelled at 37 degrees C, nor when samples were heat-denatured in the presence of formaldehyde. This suggests that nucleic acids can aggregate during centrifugation; this is discussed in relation to the molecular size of the DNA.", "contents": "The involvement of RNA in the initiation of DNA synthesis in mammalian cells. Artifacts arising during caesium-salt density-gradient centrifugation which simulate a covalent attachment of RNA to newly synthesized DNA. Artifacts were encountered during caesium salt density gradient centrifugation which simulated results expected if newly synthesized DNA is covalently attached to RNA. Newly synthesized DNA (in baby hamster kidney cells, BHK-21/C13), pulse-labelled with [3H]thymidine for 10 min at temperatures below 25 degrees C, banded at a greater buoyant density than mature [14C]DNA (heat-denatured nucleic acids) when centrifuged to equilibrium in caesium chloride gradients. Some of the newly synthesized RNA, labelled with [3H]uridine, banded at a buoyant density slightly greater than DNA in caesium sulphate gradients. These results were not obtained when nucleic acids were pulse-labelled at 37 degrees C, nor when samples were heat-denatured in the presence of formaldehyde. This suggests that nucleic acids can aggregate during centrifugation; this is discussed in relation to the molecular size of the DNA."} {"id": "PMID:1261538", "title": "The trypsin and chymotrypsin inhibitors in chick peas (Cicer arietinum L). Identification of the trypsin-reactive site, partial-amino-acid sequence and further physico-chemical properties of the major inhibitor.", "content": "The two principal isoinhibitors P-5 and P-6 isolated earlier from the seeds of chick peas (Cicer arietinum L.) by a procedure involving biospecific affinity chromatography on active, matrix-bound trypsin are shown to be the virgin and trypsin-modified forms of the same inhibitor. The virgin inhibitor P-5 consists of a single peptide chain of 66 amino acid residues cross-linked by seven disulfide bridges. Upon interaction with the matrix-bound trypsin under the conditions used the virgin inhibitor P-5 is about 50% converted to P-6 by cleavage of a single Lys-Ser linkage at position 14-15 in the molecule. The resulting tetradecapeptide remains bound to the rest of the molecule by two or four disulfide bridges, but the two fragments representing residues 1-14 and 15-66 separate readily by molecular-sieve chromatography following reductive or oxidative cleavage of the disulfide linkages. The sequence 1-25 was established by Edman degradation.", "contents": "The trypsin and chymotrypsin inhibitors in chick peas (Cicer arietinum L). Identification of the trypsin-reactive site, partial-amino-acid sequence and further physico-chemical properties of the major inhibitor. The two principal isoinhibitors P-5 and P-6 isolated earlier from the seeds of chick peas (Cicer arietinum L.) by a procedure involving biospecific affinity chromatography on active, matrix-bound trypsin are shown to be the virgin and trypsin-modified forms of the same inhibitor. The virgin inhibitor P-5 consists of a single peptide chain of 66 amino acid residues cross-linked by seven disulfide bridges. Upon interaction with the matrix-bound trypsin under the conditions used the virgin inhibitor P-5 is about 50% converted to P-6 by cleavage of a single Lys-Ser linkage at position 14-15 in the molecule. The resulting tetradecapeptide remains bound to the rest of the molecule by two or four disulfide bridges, but the two fragments representing residues 1-14 and 15-66 separate readily by molecular-sieve chromatography following reductive or oxidative cleavage of the disulfide linkages. The sequence 1-25 was established by Edman degradation."} {"id": "PMID:1261539", "title": "Molecular modifications associated with Aging of globin messenger RNA in vitro.", "content": "Using polyacrylamide gel elution-electrophoresis in aqueous medium, highly purified rabbit globin mRNA can be fractionated into several populations of molecules differing by their mean poly(A) content. Both alpha and beta globin mRNA are heterogenous with respect to their electrophoretic mobilities. With the conditions used no separation of alpha and beta globin mRNA occurs during electrophoresis. From the specific radioactivity distribution in the different mRNA fractions one can conclude that the polyadenylate sequence at the 3' end of globin mRNA molecules becomes shorter with aging. This shortening occurs on alpha as well as beta, globin mRNAs and the extent of heterogeneity in poly(A) content is similar for both globin mRNAs. Furthermore, using two different methods of mRNA fractionation (polyacrylamide gel elution-electrophoresis and elution of poly (U)-Sepharose-bound mRNA at increasing temperatures) it is shown that old mRNA molecules differ from relatively young messages in their ability to direct cell-free globin synthesis. Modifications reducing template activity in vitro thus seem to take place during globin mRNA aging.", "contents": "Molecular modifications associated with Aging of globin messenger RNA in vitro. Using polyacrylamide gel elution-electrophoresis in aqueous medium, highly purified rabbit globin mRNA can be fractionated into several populations of molecules differing by their mean poly(A) content. Both alpha and beta globin mRNA are heterogenous with respect to their electrophoretic mobilities. With the conditions used no separation of alpha and beta globin mRNA occurs during electrophoresis. From the specific radioactivity distribution in the different mRNA fractions one can conclude that the polyadenylate sequence at the 3' end of globin mRNA molecules becomes shorter with aging. This shortening occurs on alpha as well as beta, globin mRNAs and the extent of heterogeneity in poly(A) content is similar for both globin mRNAs. Furthermore, using two different methods of mRNA fractionation (polyacrylamide gel elution-electrophoresis and elution of poly (U)-Sepharose-bound mRNA at increasing temperatures) it is shown that old mRNA molecules differ from relatively young messages in their ability to direct cell-free globin synthesis. Modifications reducing template activity in vitro thus seem to take place during globin mRNA aging."} {"id": "PMID:1261540", "title": "Decreased rate of metabolism induced by a shift of the double bond in prostaglandin F 2alpha from the delta5 to the delta4 position.", "content": "The synthesis of an isomer of prostaglandin F 2alpha,9alpha,11alpha,15(S)-trihydroxyprosta-4-cis,13-transdienoic acid is described. The metabolism of this compound in the rat has been investigated. The rate of degradation by beta-oxidation was slowed down considerably. Thus 10-20% of the injected isomer was excreted in the urine unchanged indicating a longer half-life in the circulation than for prostaglandin F 2alpha. More over 2% was excreted as C20 metabolites, 11-18% as C18 metabolites and 8-15% as C16 metabolites. This relative resistance to degradation by beta-oxidation is of considerable biochemical and pharmacological interest.", "contents": "Decreased rate of metabolism induced by a shift of the double bond in prostaglandin F 2alpha from the delta5 to the delta4 position. The synthesis of an isomer of prostaglandin F 2alpha,9alpha,11alpha,15(S)-trihydroxyprosta-4-cis,13-transdienoic acid is described. The metabolism of this compound in the rat has been investigated. The rate of degradation by beta-oxidation was slowed down considerably. Thus 10-20% of the injected isomer was excreted in the urine unchanged indicating a longer half-life in the circulation than for prostaglandin F 2alpha. More over 2% was excreted as C20 metabolites, 11-18% as C18 metabolites and 8-15% as C16 metabolites. This relative resistance to degradation by beta-oxidation is of considerable biochemical and pharmacological interest."} {"id": "PMID:1261541", "title": "Regulation of phenylalanine ammonia-lyase activity in cell-suspension cultures of Petroselinum hortense. Apparent rates of enzyme synthesis and degradation.", "content": "The time courses for induced changes in the phenylalanine ammonia-lyase activity at five different stages during the growth cycle of cell-suspension cultures from parsley (Petroselinum hortense Hoffm.) were investigated. Large increases in the enzyme activity, induced either by irradiation or by dilution of a cell culture into fresh medium, were followed by an expotential decline to the initial low level. The maximum inducible level of specific enzyme activity varied within a range of about six-fold, depending on the mode of induction and the growth stage of the cell culture.", "contents": "Regulation of phenylalanine ammonia-lyase activity in cell-suspension cultures of Petroselinum hortense. Apparent rates of enzyme synthesis and degradation. The time courses for induced changes in the phenylalanine ammonia-lyase activity at five different stages during the growth cycle of cell-suspension cultures from parsley (Petroselinum hortense Hoffm.) were investigated. Large increases in the enzyme activity, induced either by irradiation or by dilution of a cell culture into fresh medium, were followed by an expotential decline to the initial low level. The maximum inducible level of specific enzyme activity varied within a range of about six-fold, depending on the mode of induction and the growth stage of the cell culture."} {"id": "PMID:1261542", "title": "Nuclease S1 cleavage and the primary structure of mitochondrial DNA.", "content": "The single-strand-specific nuclease S1 from Aspergillus oryzae rapidly converts superhelical mitochondrial DNA (African Green Monkey cells, Vero ATCC; CCL 81) into nicked circular DNA. These nicked mitochondrial DNA molecules contain two nicks, one in each strand. The phosphodiester backbones are cleaved during this reaction at or near sites that are alkali-labile. In a second slow reaction the circular mitochondrial DNA is converted into a linear duplex DNA. Permutation tests indicate that this linear DNA represents a nonpermutated collection of DNA molecules. These results suggest that two of the alkai-labile sites in the phosphodiester backbones of the mitochondrial chromosome are closely spaced on opposite strands and at specific positions.", "contents": "Nuclease S1 cleavage and the primary structure of mitochondrial DNA. The single-strand-specific nuclease S1 from Aspergillus oryzae rapidly converts superhelical mitochondrial DNA (African Green Monkey cells, Vero ATCC; CCL 81) into nicked circular DNA. These nicked mitochondrial DNA molecules contain two nicks, one in each strand. The phosphodiester backbones are cleaved during this reaction at or near sites that are alkali-labile. In a second slow reaction the circular mitochondrial DNA is converted into a linear duplex DNA. Permutation tests indicate that this linear DNA represents a nonpermutated collection of DNA molecules. These results suggest that two of the alkai-labile sites in the phosphodiester backbones of the mitochondrial chromosome are closely spaced on opposite strands and at specific positions."} {"id": "PMID:1261543", "title": "The interdependence of magnesium with spermidine and phosphoenolpyruvate in an enzyme-synthesizing system in vitro.", "content": "The DNA-dependent syntheses of different enzymes of the bacteriophages T3 and T7 were studied in an Escherichia coli system in vitro with respect to the optimal Mg2+ concentration and its interdependence with substituting (e.g. spermidine) and complexing agents (e.g. phosphoenolpyruvate). The following results were obtained. 1. The optimal conditions for the syntheses of the different enzymes were not identical. The optima for RNA polymerase synthesis were 8 mM Mg2+, 10 mM P-pyruvate and 3 mM spermidine; for S-adenosyl-L-methionine cleaving enzyme synthesis, 6 mM Mg2+, 6 mM P-pyruvate and 3 mM spermidine; and for lysozyme synthesis, 13-18 mM Mg2+, 28 mM P-pyruvate and 3-0 mM spermidine. 2. The optimal conditions for the synthesis of analog enzymes (RNA polymerases and lysozymes) from the two templates were identical with experimental error. 3. Mg2+ and spermidine substituted for each other in relation to the number of their charges. 4. The apparent complexing of one Mg2+ molecule required the addition of 3-5 P pyruvate molecules. 5. Under the optimal conditions the enzyme-synthesizing activity was higher by more than a factor of 10 compared to previously described systems.", "contents": "The interdependence of magnesium with spermidine and phosphoenolpyruvate in an enzyme-synthesizing system in vitro. The DNA-dependent syntheses of different enzymes of the bacteriophages T3 and T7 were studied in an Escherichia coli system in vitro with respect to the optimal Mg2+ concentration and its interdependence with substituting (e.g. spermidine) and complexing agents (e.g. phosphoenolpyruvate). The following results were obtained. 1. The optimal conditions for the syntheses of the different enzymes were not identical. The optima for RNA polymerase synthesis were 8 mM Mg2+, 10 mM P-pyruvate and 3 mM spermidine; for S-adenosyl-L-methionine cleaving enzyme synthesis, 6 mM Mg2+, 6 mM P-pyruvate and 3 mM spermidine; and for lysozyme synthesis, 13-18 mM Mg2+, 28 mM P-pyruvate and 3-0 mM spermidine. 2. The optimal conditions for the synthesis of analog enzymes (RNA polymerases and lysozymes) from the two templates were identical with experimental error. 3. Mg2+ and spermidine substituted for each other in relation to the number of their charges. 4. The apparent complexing of one Mg2+ molecule required the addition of 3-5 P pyruvate molecules. 5. Under the optimal conditions the enzyme-synthesizing activity was higher by more than a factor of 10 compared to previously described systems."} {"id": "PMID:1261544", "title": "L-alpha-Hydroxyacid oxidase isozymes. Purification and molecular properties.", "content": "L-alpha-Hydroxyacid oxidase isozymes from rat liver (A isozyme) and kidney (B isozyme) have been isolated in a high state of purity with specific activities of 61 and 14.7 microkatals per gram protein respectively. The subunit molecular weights determined by sodium dodecylsulphate polyacrylamide gel electrophoresis were 40000 +/- 3000; the mouse A and B isozymes were also partially purified and their subunit molecular weights shown to be 37000.", "contents": "L-alpha-Hydroxyacid oxidase isozymes. Purification and molecular properties. L-alpha-Hydroxyacid oxidase isozymes from rat liver (A isozyme) and kidney (B isozyme) have been isolated in a high state of purity with specific activities of 61 and 14.7 microkatals per gram protein respectively. The subunit molecular weights determined by sodium dodecylsulphate polyacrylamide gel electrophoresis were 40000 +/- 3000; the mouse A and B isozymes were also partially purified and their subunit molecular weights shown to be 37000."} {"id": "PMID:1261545", "title": "The purification and properties of cyclohexanone oxygenase from Nocardia globerula CL1 and Acinetobacter NCIB 9871.", "content": "1. Cyclohexanone oxygenases from Norcardia globerula CL1 and Acinetobacter NCIB 9871 have been purified 12-fold and 35-fold respectively and each gives a single symmetrical sedimentation peak in the ultracentrifuge and a single protein band on 2.25 nm average pore radius polyacrylamide gels. 2. The enzyme from N. globerula has a molecular weight of 53000 while that from Acinetobacter has a molecular weight of about 59000. Each is a single polypeptide chain with one mole of bound FAD per mole of protein that does not dissociate during purification. Acidification of the Acinetobacter enzyme in the presence of (NH4)2SO4 releases the bound FAD and yields native apoenzyme from which the active holoenzyme can be reconstituted. The apparent dissociation constant for the FAD is 40 nM.", "contents": "The purification and properties of cyclohexanone oxygenase from Nocardia globerula CL1 and Acinetobacter NCIB 9871. 1. Cyclohexanone oxygenases from Norcardia globerula CL1 and Acinetobacter NCIB 9871 have been purified 12-fold and 35-fold respectively and each gives a single symmetrical sedimentation peak in the ultracentrifuge and a single protein band on 2.25 nm average pore radius polyacrylamide gels. 2. The enzyme from N. globerula has a molecular weight of 53000 while that from Acinetobacter has a molecular weight of about 59000. Each is a single polypeptide chain with one mole of bound FAD per mole of protein that does not dissociate during purification. Acidification of the Acinetobacter enzyme in the presence of (NH4)2SO4 releases the bound FAD and yields native apoenzyme from which the active holoenzyme can be reconstituted. The apparent dissociation constant for the FAD is 40 nM."} {"id": "PMID:1261546", "title": "Structure of flavin adducts with acetylenic substrates. Chemistry of monoamine oxidase and lactate oxidase inhibition.", "content": "The photoreaction of flavoquinones (lumiflavin, riboflavin, FMN etc. and their 3-alkylated derivatives) with propargylamine-type acetylenic substrates, R4 -Calpha identical to Cbeta -CgammaHR3 -NR2R1, yields a mixture of two adducts,which result from covalent Calpha fixation of the Cgamma-deprotonated substrate to either position C(4a) or N(5) in the flavin nucleus. The N(5) adduct is a dihydroflavin-5-trimethine-cyanine with very intense (xi greater than 20000 M-1 cm-1) absorption maxima in the region 380-450 nm depending on the R1,R2. This absorption allows recognition of minute amounts of this species of flavocyanine even in complex mixtures. Flavocyanines can be reconverted to starting flavin by base. It spectral properties are identical with those obtained for the pargyline-flavin inhibitor complex from bovine kidney or pig liver monoamine oxidase.", "contents": "Structure of flavin adducts with acetylenic substrates. Chemistry of monoamine oxidase and lactate oxidase inhibition. The photoreaction of flavoquinones (lumiflavin, riboflavin, FMN etc. and their 3-alkylated derivatives) with propargylamine-type acetylenic substrates, R4 -Calpha identical to Cbeta -CgammaHR3 -NR2R1, yields a mixture of two adducts,which result from covalent Calpha fixation of the Cgamma-deprotonated substrate to either position C(4a) or N(5) in the flavin nucleus. The N(5) adduct is a dihydroflavin-5-trimethine-cyanine with very intense (xi greater than 20000 M-1 cm-1) absorption maxima in the region 380-450 nm depending on the R1,R2. This absorption allows recognition of minute amounts of this species of flavocyanine even in complex mixtures. Flavocyanines can be reconverted to starting flavin by base. It spectral properties are identical with those obtained for the pargyline-flavin inhibitor complex from bovine kidney or pig liver monoamine oxidase."} {"id": "PMID:1261547", "title": "Synthesis of albumin via a precursor protein in cell suspensions from rat liver.", "content": "The mechanism of the biosynthesis of albumin was studied in cell suspensions from rat liver. The cells were prepared by continuous perfusion of the liver in situ with 0.05% collagenase and 0.10% hyaluronidase and incubated under conditions optimized for the incorporation of amino acids into protein. Seven minutes after starting the incubation L-[1-14C]leucine was added, followed after 25 min by a 15 or 30-min chase with an 830-fold excess of non-radioactive L-leucine. Total protein, an albumin-like protein, and albumin were isolated from samples withdrawn immediately of total protein was found to remain constant after addition of the non-radioactive L-leucine, whereas that of the albumin-like protein decreased and that of albumin increased with incubation time. The increase in albumin radioactivity accounted for the decrease in radioactivity of the albumin-like protein, suggesting that the latter is a precursor of albumin. The precursor protein differed from albumin by an oligopeptide extension at the N-terminal end.", "contents": "Synthesis of albumin via a precursor protein in cell suspensions from rat liver. The mechanism of the biosynthesis of albumin was studied in cell suspensions from rat liver. The cells were prepared by continuous perfusion of the liver in situ with 0.05% collagenase and 0.10% hyaluronidase and incubated under conditions optimized for the incorporation of amino acids into protein. Seven minutes after starting the incubation L-[1-14C]leucine was added, followed after 25 min by a 15 or 30-min chase with an 830-fold excess of non-radioactive L-leucine. Total protein, an albumin-like protein, and albumin were isolated from samples withdrawn immediately of total protein was found to remain constant after addition of the non-radioactive L-leucine, whereas that of the albumin-like protein decreased and that of albumin increased with incubation time. The increase in albumin radioactivity accounted for the decrease in radioactivity of the albumin-like protein, suggesting that the latter is a precursor of albumin. The precursor protein differed from albumin by an oligopeptide extension at the N-terminal end."} {"id": "PMID:1261548", "title": "Influence of chain length and unsaturation on the effects of fatty acids on phosphoglyceride biosynthesis in isolated rat and pig hepatocytes.", "content": "Hepatocytes isolated from rat or pig by collagenase perfusion were incubated with [3H]glcyerol and different albumin-bount fatty acids. Among C22 fatty acids docosahexaenoic acid stimulated phosphatidylethanolamine synthesis in rat hepatocytes most effectively. Addition of docosahexaenoic acid plus either palmitic or stearic acid resulted almost in the same stimulation whereas combinations of this acid with lauric or myristic acid had no effect. Lauric acid and myristic acid alone inhibited phosphatidylethanolamine synthesis. The chain length specificity for monoenoic fatty acids was similar, the hexadecenoic and octadecenoic acids (both cis and trans) being most stimulatory. The addition of 0.2 mM ethanolamine markedly stimulated phosphatidylethanolamine synthesis, but most effects of fatty acids were similar in its presence or absence.", "contents": "Influence of chain length and unsaturation on the effects of fatty acids on phosphoglyceride biosynthesis in isolated rat and pig hepatocytes. Hepatocytes isolated from rat or pig by collagenase perfusion were incubated with [3H]glcyerol and different albumin-bount fatty acids. Among C22 fatty acids docosahexaenoic acid stimulated phosphatidylethanolamine synthesis in rat hepatocytes most effectively. Addition of docosahexaenoic acid plus either palmitic or stearic acid resulted almost in the same stimulation whereas combinations of this acid with lauric or myristic acid had no effect. Lauric acid and myristic acid alone inhibited phosphatidylethanolamine synthesis. The chain length specificity for monoenoic fatty acids was similar, the hexadecenoic and octadecenoic acids (both cis and trans) being most stimulatory. The addition of 0.2 mM ethanolamine markedly stimulated phosphatidylethanolamine synthesis, but most effects of fatty acids were similar in its presence or absence."} {"id": "PMID:1261549", "title": "An enzyme complex for the dehydrogenation of phytoene in Phycomyces.", "content": "Phycomyces strain C5, carrying mutation carB10, accumulates phytoene instead of beta-carotene. Heterokaryons containing C5 nuclei and different other nuclei carrying the wild type carB allele accumulate significant amounts of phytofluene, zota-carotene and neurosporene. From quantitative analyses of carotenes and nuclear proportions in the heterokaryons we conclude that four copies of the carB gene product, assembled in an enzyme complex, act sequentially in the conversion of phytoene to lycopene.", "contents": "An enzyme complex for the dehydrogenation of phytoene in Phycomyces. Phycomyces strain C5, carrying mutation carB10, accumulates phytoene instead of beta-carotene. Heterokaryons containing C5 nuclei and different other nuclei carrying the wild type carB allele accumulate significant amounts of phytofluene, zota-carotene and neurosporene. From quantitative analyses of carotenes and nuclear proportions in the heterokaryons we conclude that four copies of the carB gene product, assembled in an enzyme complex, act sequentially in the conversion of phytoene to lycopene."} {"id": "PMID:1261550", "title": "Synthesis of a cleavable protein-crosslinking reagent for the investigation of ribosome structure.", "content": "This communication describes a simple method for synthesizing cleavable bifunctional imido esters of different chain lengths. These reagents, which form covalent crosslinks between lysine residues of proteins, contain a disulfide bond which is cleaved under mild conditions by reducing agents such as 2-mercaptoethanol. The reagents are synthesized via the dithiobisnitrile which is prepared in high yield by reacting the appropriate omega-activated nitrile with sodium polysulfide and is then converted quantitatively to the diimidate. Three such reagents were prepared: dimethyl 3.3'-dithiobispropionimidate, dimethyl 4,4'-dithiobisbutyrimidate, and dimethyl 6-6'-dithiobiscaproimidate. The first was synthesized from acrylonitrile, and the others from the appropriate omega-bromonitriles. Experiments with the bispropionimidate and a test protein, pancreatic ribonuclease, have shown the reagent to be effective in producing multimeric crosslinked complexes, from which monomeric proteins can recovered after treatment with 2-mercaptoethanol. The reagents are suitable for studies of ribosomal structure.", "contents": "Synthesis of a cleavable protein-crosslinking reagent for the investigation of ribosome structure. This communication describes a simple method for synthesizing cleavable bifunctional imido esters of different chain lengths. These reagents, which form covalent crosslinks between lysine residues of proteins, contain a disulfide bond which is cleaved under mild conditions by reducing agents such as 2-mercaptoethanol. The reagents are synthesized via the dithiobisnitrile which is prepared in high yield by reacting the appropriate omega-activated nitrile with sodium polysulfide and is then converted quantitatively to the diimidate. Three such reagents were prepared: dimethyl 3.3'-dithiobispropionimidate, dimethyl 4,4'-dithiobisbutyrimidate, and dimethyl 6-6'-dithiobiscaproimidate. The first was synthesized from acrylonitrile, and the others from the appropriate omega-bromonitriles. Experiments with the bispropionimidate and a test protein, pancreatic ribonuclease, have shown the reagent to be effective in producing multimeric crosslinked complexes, from which monomeric proteins can recovered after treatment with 2-mercaptoethanol. The reagents are suitable for studies of ribosomal structure."} {"id": "PMID:1261551", "title": "Purification of the mRNAs for Ewe alphaS-casein and beta-casein by immunoprecipitation of polysomes.", "content": "Specific polysomes synthesizing alphas-casein and beta-casein were immunoprecipitated from total polysomes of the lactating ewe mammary gland. The polysome - anti-casein complex was immunoprecipitated by anti-immunoglobulins. 22%, 32% and 10% of polysomes were immunoprecipitated with saturating amounts of anti-alphas-casein, anti-beta-casein and anti-chi-casein respectively. Poly(U)-Sepharose chromatography of the immunoprecipitated RNAs permitted the isolation of the corresponding poly(A)-containing RNA which migrated as one major band in polyacrylamide gel electrophoresis. As judged by the contamination with the messenger activity for one of the other caseins, the purity of the mRNA for alphas-casein as well as for beta-casein was estimated to be between 75% and 80%.", "contents": "Purification of the mRNAs for Ewe alphaS-casein and beta-casein by immunoprecipitation of polysomes. Specific polysomes synthesizing alphas-casein and beta-casein were immunoprecipitated from total polysomes of the lactating ewe mammary gland. The polysome - anti-casein complex was immunoprecipitated by anti-immunoglobulins. 22%, 32% and 10% of polysomes were immunoprecipitated with saturating amounts of anti-alphas-casein, anti-beta-casein and anti-chi-casein respectively. Poly(U)-Sepharose chromatography of the immunoprecipitated RNAs permitted the isolation of the corresponding poly(A)-containing RNA which migrated as one major band in polyacrylamide gel electrophoresis. As judged by the contamination with the messenger activity for one of the other caseins, the purity of the mRNA for alphas-casein as well as for beta-casein was estimated to be between 75% and 80%."} {"id": "PMID:1261552", "title": "Methylation analysis of glucosaminitol and glucosaminyl-glucosaminitol disaccharides. Formation of 2-deoxy-2-(N-acetylacetamido)-glucitol derivatives.", "content": "N-Acetylglucosaminitol, N-acetylglucosaminyl-beta 1',4-N-acetylglucosaminitol (chitobiitol), the corresponding trimer (chitotriitol) and N-acetylgucosaminyl-beta 1'6-N-acetylglucosaminitol were subjected to methylation analysis using combined gas-liquid chromatography/mass spectrometry. The preparation were subjected to permethylation according to Hakomori, followed by acid hydrolysis, reduction and peracetylation. From N-acetylglucosaminitol and its 4-0 and 6-0 substituted derivatives, methylated N-acetylacetamido derivatives were obtained. The possible conditions for the formation of these products are discussed.", "contents": "Methylation analysis of glucosaminitol and glucosaminyl-glucosaminitol disaccharides. Formation of 2-deoxy-2-(N-acetylacetamido)-glucitol derivatives. N-Acetylglucosaminitol, N-acetylglucosaminyl-beta 1',4-N-acetylglucosaminitol (chitobiitol), the corresponding trimer (chitotriitol) and N-acetylgucosaminyl-beta 1'6-N-acetylglucosaminitol were subjected to methylation analysis using combined gas-liquid chromatography/mass spectrometry. The preparation were subjected to permethylation according to Hakomori, followed by acid hydrolysis, reduction and peracetylation. From N-acetylglucosaminitol and its 4-0 and 6-0 substituted derivatives, methylated N-acetylacetamido derivatives were obtained. The possible conditions for the formation of these products are discussed."} {"id": "PMID:1261553", "title": "[alpha-L-Rhamnosidase from Fagopyrum esculentum: purification and some properties (author's transl)].", "content": "An alpha-L-rhamnosidase from the seeds of Fagopyrum esculentum (saracen corn) has previously been identified, and the effect of the enzyme on rhamnoisic bonds has been studied with various flavonoid glycosides. This alpha-L-rhamnosidase can be useful in structural studies, and a preliminary report of this study has appeared. The present paper describes the extensive purification of the enzyme and the determination of its properties. The purification involved extraction, ammonium sulfate fractionation and chromatography on Sephadex G 75, DEAE-Sephadex and Ultrogel AcA-44. The alpha-L-rhamnosidase was purified about 9600 fold and the final enzyme preparation was practically pure according to the criteria of disc electrophoresis. The molecular weight of this alpha-L-rhamnosidase, calculated from data obtained by disc gel electrophoresis and gel filtration, was about 70 000. Isoelectric focusing established the isoelectric point to be 3.7. The behaviour of the enzyme on a concanavalin-A-Sepharose column suggests the presence of residues resembling alpha-D-mannose or alpha-D-glucose in the protein. The various kinetic parameters, Kcat, Km and the Kcat/Km ratio have been determined at pH 5 on the following substrates: p-nitrophenyl-alpha-L-rhamnoside and rutinose (6-O-alpha-L-rhamnosyl-D-glucopyranose). All kinetics exhibit a Michaelian behaviour and the Km for the former substrate was 0.33 mM and for the latter, 2.2 mM. The Kcat/Km ratio corroborates the greater specificity of the enzyme for p-nitrophenyl-alpha-L-rhamnoside. L-Rhamnose, L-lyxose, 6-deoxy-D-glucose and methyl-alpha-D-mannoside were shown to behave strictly as competitive inhibitors of alpha-L-rhamnosidase activity; it seems that the methyl group of L-rhamnose is important for substrate binding to the enzyme.", "contents": "[alpha-L-Rhamnosidase from Fagopyrum esculentum: purification and some properties (author's transl)]. An alpha-L-rhamnosidase from the seeds of Fagopyrum esculentum (saracen corn) has previously been identified, and the effect of the enzyme on rhamnoisic bonds has been studied with various flavonoid glycosides. This alpha-L-rhamnosidase can be useful in structural studies, and a preliminary report of this study has appeared. The present paper describes the extensive purification of the enzyme and the determination of its properties. The purification involved extraction, ammonium sulfate fractionation and chromatography on Sephadex G 75, DEAE-Sephadex and Ultrogel AcA-44. The alpha-L-rhamnosidase was purified about 9600 fold and the final enzyme preparation was practically pure according to the criteria of disc electrophoresis. The molecular weight of this alpha-L-rhamnosidase, calculated from data obtained by disc gel electrophoresis and gel filtration, was about 70 000. Isoelectric focusing established the isoelectric point to be 3.7. The behaviour of the enzyme on a concanavalin-A-Sepharose column suggests the presence of residues resembling alpha-D-mannose or alpha-D-glucose in the protein. The various kinetic parameters, Kcat, Km and the Kcat/Km ratio have been determined at pH 5 on the following substrates: p-nitrophenyl-alpha-L-rhamnoside and rutinose (6-O-alpha-L-rhamnosyl-D-glucopyranose). All kinetics exhibit a Michaelian behaviour and the Km for the former substrate was 0.33 mM and for the latter, 2.2 mM. The Kcat/Km ratio corroborates the greater specificity of the enzyme for p-nitrophenyl-alpha-L-rhamnoside. L-Rhamnose, L-lyxose, 6-deoxy-D-glucose and methyl-alpha-D-mannoside were shown to behave strictly as competitive inhibitors of alpha-L-rhamnosidase activity; it seems that the methyl group of L-rhamnose is important for substrate binding to the enzyme."} {"id": "PMID:1261554", "title": "Effect of specific antibodies on D-glyceraldehyde-3-phosphate dehydrogenase.", "content": "The inhibition of rat skeletal muscle glyceraldehyde-3-phosphate dehydrogenase by specific antibodies produced in rabbits has been studied. The results suggest that no influence on the enzyme active site is caused by the interaction with antibody, the inhibition being due entirely to the restricted accessibility for substrates of a part of dehydrogenase molecules included in the immune precipitate. Soluble complexes of the enzyme with monovalent Fab antibody fragments retain full catalytic activity. Modification of 8 -SH groups per mole of glyceraldehyde-3-phosphate dehydrogenase with p-chloromercuribenzoate results in no alterations in the quantitative precipitin curve, thus supporting the conclusion about the different localization of species-specific antigenic determinants of the enzyme and its active center. Interaction with monovalent Fab fragments of antibody stabilizes the structure of the dehydrogenase. Eight molar equivalents of Fab fragments almost completely protect the enzyme from cold inactivation in the presence of 0.15 M NaCl. Complex formation with Fab fragments does not prevent, however, the ADP-induced inactivation of the enzyme.", "contents": "Effect of specific antibodies on D-glyceraldehyde-3-phosphate dehydrogenase. The inhibition of rat skeletal muscle glyceraldehyde-3-phosphate dehydrogenase by specific antibodies produced in rabbits has been studied. The results suggest that no influence on the enzyme active site is caused by the interaction with antibody, the inhibition being due entirely to the restricted accessibility for substrates of a part of dehydrogenase molecules included in the immune precipitate. Soluble complexes of the enzyme with monovalent Fab antibody fragments retain full catalytic activity. Modification of 8 -SH groups per mole of glyceraldehyde-3-phosphate dehydrogenase with p-chloromercuribenzoate results in no alterations in the quantitative precipitin curve, thus supporting the conclusion about the different localization of species-specific antigenic determinants of the enzyme and its active center. Interaction with monovalent Fab fragments of antibody stabilizes the structure of the dehydrogenase. Eight molar equivalents of Fab fragments almost completely protect the enzyme from cold inactivation in the presence of 0.15 M NaCl. Complex formation with Fab fragments does not prevent, however, the ADP-induced inactivation of the enzyme."} {"id": "PMID:1261555", "title": "Carbohydrate in pancreatic ribonucleases.", "content": "A survey of the presence and compositions of carbohydrate chains attached to pancreatic ribonucleases is given. Carbohydrate chains may occur at asparagine residues in Asn-X-Ser/Thr sequences at four exposed sites of the molecule (positions 21, 34, 62 and 76). These sites form part of highly variant sequences in pancreatic ribonucleases with the consequence that the enzymes from very closely related species may differ in the presence or absence of carbohydrate. In a number of ribonucleases Asn-X-Ser/Thr sequences occur which carry carbohydrate in only a part of the molecules. The occurrence of Asn-X-Ser/Thr sequences entirely without any carbohydrate also has been demonstrated. Compositions of the carbohydrate moieties of ribonucleases from cow, sheep, pig, whales, giraffe, okapi, moose, horse, coypu, chinchilla, and guinea-pig are presented. Striking differences in complexity have been found, both between chains attached to the same site in different species (cow and giraffe), between chains attached to different sites of the same enzyme in one-species (pig) and even between chains attached to the same site in a single species (chinchilla).", "contents": "Carbohydrate in pancreatic ribonucleases. A survey of the presence and compositions of carbohydrate chains attached to pancreatic ribonucleases is given. Carbohydrate chains may occur at asparagine residues in Asn-X-Ser/Thr sequences at four exposed sites of the molecule (positions 21, 34, 62 and 76). These sites form part of highly variant sequences in pancreatic ribonucleases with the consequence that the enzymes from very closely related species may differ in the presence or absence of carbohydrate. In a number of ribonucleases Asn-X-Ser/Thr sequences occur which carry carbohydrate in only a part of the molecules. The occurrence of Asn-X-Ser/Thr sequences entirely without any carbohydrate also has been demonstrated. Compositions of the carbohydrate moieties of ribonucleases from cow, sheep, pig, whales, giraffe, okapi, moose, horse, coypu, chinchilla, and guinea-pig are presented. Striking differences in complexity have been found, both between chains attached to the same site in different species (cow and giraffe), between chains attached to different sites of the same enzyme in one-species (pig) and even between chains attached to the same site in a single species (chinchilla)."} {"id": "PMID:1261556", "title": "Mechanism of the stimulatory effect of fructose on ethanol oxidation in perfused rat liver.", "content": "The stimulatory effect of fructose on ethanol oxidation was studied in livers from fasted rats perfused with Krebs-Henseleit-bicarbonate buffer in a non-recirculating system. Two series of experiments were performed: (A) ethanol was infused with stepwise increasing concentrations (0.1-20 mM) in the presence of 4 mM fructose; (B) fructose was infused with stepwise increasing concentrations (0.5-10 mM) in the presence of 2 mM ethanol. From measured metabolic rates the following parameters were calculated: energy-rich phosphates consumed for fructose metabolism which were provided from oxidative phosphorylation (delta approximately P); reducing equivalents derived from stimulated ethanol utilization which were disposed by mitochondrial oxidation (delta2H). Under the various conditions studied a linear relationship between these parameters was observed. The ratio delta approximately P/delta2H was about 2.0. It is suggested that fructose stimulates ethanol oxidation indirectly by increasing the energy consumption of the liver due to the production of glucose from fructose. Consequetnly, the rate of oxidative phosphorylation is increased and, therefore, the capacity of the respiratory chain for oxidizing reducing equivalents derived from ethanol is enhanced. The data support the more general hypothesis that the rate of ethanol oxidation depend upon the rate of hepatic energy consumption in a given metabolic state.", "contents": "Mechanism of the stimulatory effect of fructose on ethanol oxidation in perfused rat liver. The stimulatory effect of fructose on ethanol oxidation was studied in livers from fasted rats perfused with Krebs-Henseleit-bicarbonate buffer in a non-recirculating system. Two series of experiments were performed: (A) ethanol was infused with stepwise increasing concentrations (0.1-20 mM) in the presence of 4 mM fructose; (B) fructose was infused with stepwise increasing concentrations (0.5-10 mM) in the presence of 2 mM ethanol. From measured metabolic rates the following parameters were calculated: energy-rich phosphates consumed for fructose metabolism which were provided from oxidative phosphorylation (delta approximately P); reducing equivalents derived from stimulated ethanol utilization which were disposed by mitochondrial oxidation (delta2H). Under the various conditions studied a linear relationship between these parameters was observed. The ratio delta approximately P/delta2H was about 2.0. It is suggested that fructose stimulates ethanol oxidation indirectly by increasing the energy consumption of the liver due to the production of glucose from fructose. Consequetnly, the rate of oxidative phosphorylation is increased and, therefore, the capacity of the respiratory chain for oxidizing reducing equivalents derived from ethanol is enhanced. The data support the more general hypothesis that the rate of ethanol oxidation depend upon the rate of hepatic energy consumption in a given metabolic state."} {"id": "PMID:1261557", "title": "Isolation and characterization of the 'photosynthetic' phosphoglycerate kinase from Beta vulgaris.", "content": "1. Phosphoglycerate kinase has been isolated from a photosynthetic plant tissue, Beta vulgaris leaves. The purification procedure is described. 2. The best preparation had no detectable impurity on electrophoresis, and had a specific activity comparable with the same enzyme from other sources. 3. The molecular weight was not distinguishably different from that of the yeast or muscle enzyme, as measured by polyacrylamide-dodecylsulphate electrophoresis. Measurement of aromatic and sulphydryl residues indicated a close similarity with the yeast enzyme. The enzyme appears to have substantially lower isoelectric point than phosphoglycerate kinases from other sources. 4. Kinetic studies indicated that the affinities for the substrates MgATP2- and 3-phosphoglycerate were not significantly different from those of the 'glycolytic' yeast enzyme. There was no evidence that the B. vulgaris enzyme had specific properties making it more suitable for its gluconeogenic rather than glycolytic role.", "contents": "Isolation and characterization of the 'photosynthetic' phosphoglycerate kinase from Beta vulgaris. 1. Phosphoglycerate kinase has been isolated from a photosynthetic plant tissue, Beta vulgaris leaves. The purification procedure is described. 2. The best preparation had no detectable impurity on electrophoresis, and had a specific activity comparable with the same enzyme from other sources. 3. The molecular weight was not distinguishably different from that of the yeast or muscle enzyme, as measured by polyacrylamide-dodecylsulphate electrophoresis. Measurement of aromatic and sulphydryl residues indicated a close similarity with the yeast enzyme. The enzyme appears to have substantially lower isoelectric point than phosphoglycerate kinases from other sources. 4. Kinetic studies indicated that the affinities for the substrates MgATP2- and 3-phosphoglycerate were not significantly different from those of the 'glycolytic' yeast enzyme. There was no evidence that the B. vulgaris enzyme had specific properties making it more suitable for its gluconeogenic rather than glycolytic role."} {"id": "PMID:1261558", "title": "Catabolism of cholesterol by bovine adrenal-cortex enzymes: in vitro formation of oxygenated sterols and side-chain cleavage products.", "content": "The identification of sterols and steroids formed by incubation of [7alph-3H, 26-14C]cholesterol with mitochondrial enzymes from bovine adrenal cortex is reported. Only 17% of the radioactivity associated with cholesterol metabolites was found in pregnenolone, whereas 15% was reliable to oxygenated sterols and 6% to steroid compounds. The significance of the formation of these compounds is discussed particularly as regards oxygenated cholesterol derivatives.", "contents": "Catabolism of cholesterol by bovine adrenal-cortex enzymes: in vitro formation of oxygenated sterols and side-chain cleavage products. The identification of sterols and steroids formed by incubation of [7alph-3H, 26-14C]cholesterol with mitochondrial enzymes from bovine adrenal cortex is reported. Only 17% of the radioactivity associated with cholesterol metabolites was found in pregnenolone, whereas 15% was reliable to oxygenated sterols and 6% to steroid compounds. The significance of the formation of these compounds is discussed particularly as regards oxygenated cholesterol derivatives."} {"id": "PMID:1261559", "title": "[Study of the biosynthesis of phleic acids, polyunsaturated fatty acids synthesised by Mycobacterium phlei (author's transl)].", "content": "Because of their structures, phleic acids (general formula: CH3-(CH2)m-(CH=CH-CH2-CH2)n-CO2H; main component: m = 14, n = 5) cannot be synthesized by the same kinds of enzymatic systems as other natural polyunsaturated fatty acids. By using specifically labelled 14C compounds, we have tested the ability of different molecules to be incorporated in the phleate skeletons by Mycobacterium phlei. The localisation of radioactive carbon atoms has been studied by chemical degradation of labelled phleates, isolation and purification of the degradation products, and determination of their specific radioactivity. When M. phlei cells are incubated with labelled acetate, the unsaturated and saturated parts of the molecules of phleic acids are unequally labelled. The radioactivity of succinate monoester on the one hand and fatty acids (mixture of myristic and palmitic acids) on the other hand, measured after oxidative degradation of phleate esters, shows a constant ratio under definite conditions. Whether [1-14C]acetate or [2-14C]acetate is used for incubation, the same ratio is observed. Therefore acetate is the precursor of the unsaturated part as well as of the saturated part of the phleate molecules. By using labelled fatty acid esters, it has been found that palmitic acid is the precursor of phleates with m = 14, while myristic acid is the precursor of phleates with m = 12. Stearic and eicosanoic acids are not incorporated without degradation. The hypothesis of a condensation of a saturated fatty acid with a preformed polyunsaturated molecule was examined. Search for such a molecule in the lipids of M. phlei gives negative results. Pentaunsaturated phleate arising from palmitate is more abundant than pentaunsaturated phleate arising from myristate, while the reverse is true for hexaunsaturated phleates. These observations make very unlikely such an hypothesis. An elongation process fits well with the observed facts provided that this process involves elongation by two acetate units simultaneously, making elongation by four carbon atoms at a time. Such a requirement would be easily satisfied if two molecules of acetate are condensed together before their utilization in the elongation process. In such a hypothetical process, crotonate would be the most probable substrate of the elongation reaction.", "contents": "[Study of the biosynthesis of phleic acids, polyunsaturated fatty acids synthesised by Mycobacterium phlei (author's transl)]. Because of their structures, phleic acids (general formula: CH3-(CH2)m-(CH=CH-CH2-CH2)n-CO2H; main component: m = 14, n = 5) cannot be synthesized by the same kinds of enzymatic systems as other natural polyunsaturated fatty acids. By using specifically labelled 14C compounds, we have tested the ability of different molecules to be incorporated in the phleate skeletons by Mycobacterium phlei. The localisation of radioactive carbon atoms has been studied by chemical degradation of labelled phleates, isolation and purification of the degradation products, and determination of their specific radioactivity. When M. phlei cells are incubated with labelled acetate, the unsaturated and saturated parts of the molecules of phleic acids are unequally labelled. The radioactivity of succinate monoester on the one hand and fatty acids (mixture of myristic and palmitic acids) on the other hand, measured after oxidative degradation of phleate esters, shows a constant ratio under definite conditions. Whether [1-14C]acetate or [2-14C]acetate is used for incubation, the same ratio is observed. Therefore acetate is the precursor of the unsaturated part as well as of the saturated part of the phleate molecules. By using labelled fatty acid esters, it has been found that palmitic acid is the precursor of phleates with m = 14, while myristic acid is the precursor of phleates with m = 12. Stearic and eicosanoic acids are not incorporated without degradation. The hypothesis of a condensation of a saturated fatty acid with a preformed polyunsaturated molecule was examined. Search for such a molecule in the lipids of M. phlei gives negative results. Pentaunsaturated phleate arising from palmitate is more abundant than pentaunsaturated phleate arising from myristate, while the reverse is true for hexaunsaturated phleates. These observations make very unlikely such an hypothesis. An elongation process fits well with the observed facts provided that this process involves elongation by two acetate units simultaneously, making elongation by four carbon atoms at a time. Such a requirement would be easily satisfied if two molecules of acetate are condensed together before their utilization in the elongation process. In such a hypothetical process, crotonate would be the most probable substrate of the elongation reaction."} {"id": "PMID:1261560", "title": "Acetylcholinesterase and its association with lipid.", "content": "Human erythrocyte acetylcholinesterase preparations which vary in lipid content, from lipid-rich to lipid-poor, have been successfully prepared using deoxycholate. It was found that the lipid content of the enzyme decreased gradually as the deoxycholate concentration used in its preparation was increased. The binding of lipid to lipid-poor preparations of the enzyme has been investigated. It was found that the activity of such preparations was highly dependent on their phospholipid contents. Maximum specific activity was associated with a fixed phospholipid content. The lipid-poor enzyme was highly activated by addition of either endogenous(membrane) or exogenous lipid. Based on the data presented, it was concluded that acetylcholinesterase is a phospholipoprotein, and its activity is highly dependent on its phospholipid component.", "contents": "Acetylcholinesterase and its association with lipid. Human erythrocyte acetylcholinesterase preparations which vary in lipid content, from lipid-rich to lipid-poor, have been successfully prepared using deoxycholate. It was found that the lipid content of the enzyme decreased gradually as the deoxycholate concentration used in its preparation was increased. The binding of lipid to lipid-poor preparations of the enzyme has been investigated. It was found that the activity of such preparations was highly dependent on their phospholipid contents. Maximum specific activity was associated with a fixed phospholipid content. The lipid-poor enzyme was highly activated by addition of either endogenous(membrane) or exogenous lipid. Based on the data presented, it was concluded that acetylcholinesterase is a phospholipoprotein, and its activity is highly dependent on its phospholipid component."} {"id": "PMID:1261561", "title": "[Separation of structural studies of the molecular species of monomycolates and dimycolates of alpha-D-trehalose present in Mycobacterium phlei (author's transl)].", "content": "Mixtures of dimycolates of alpha-D-trehalose (cord factor) and monomycolates have been isolated from Mycobacterium phlei and separated as trimethylsilyl derivatives according to the polarity of the fatty acid residues. The free glycolipids can be recovered by mild hydrolysis. Silylation and disilylation reactions did not induce any isomerisation. The structure of these trehalose esters has been determined by using a series of reactions elaborated on synthetic acyl-sugar models. Free hydroxyl groups are transformed into tetrahydropyran ethers, deacylated by dimsyl sodium, methylated and the sugar derivatives are hydrolyzed. The O-methyl-sugars obtained contain a methyl ether group located at the position where the acyl group was present initially. Identification by gas chromatography of the O-methyl-sugars thus allows the location of the fatty acid residues in the glycolipid. It has been demonstrated that no migration occurs. Two types of 6-monomycoloyl-alpha-D-trehalose have been isolated, differing by the nature of the mycolic acid residues. One of them, called MA, contains \"alpha-phlei mycolic acid\". The other one, called MB, contains \"gamma-phlei mycolic acid\" which is the ester of 2-eicosanol with the omega-carboxyl function of a dicarboxylic mycolic acid. Three types of 6,6'-dimycoloyl-alpha-D-trehalose (cord factor) have been obtained. Two of them are symmetrical diesters, containing either two residues of alpha-mycolic acid, or two residues of gamma-mycolic acid. The last one is an unsymmetrical diester, the hydrolysis of which gives one mole of alpha-mycolic acid and one mole of gamma-mycolic acid. The ratio of the different diesters in the cord factor fraction might be explained by some equilibrium between the different 6-ester groups or by a transformation in situ of one species into another one by biochemical modification of the mycolic acid residues.", "contents": "[Separation of structural studies of the molecular species of monomycolates and dimycolates of alpha-D-trehalose present in Mycobacterium phlei (author's transl)]. Mixtures of dimycolates of alpha-D-trehalose (cord factor) and monomycolates have been isolated from Mycobacterium phlei and separated as trimethylsilyl derivatives according to the polarity of the fatty acid residues. The free glycolipids can be recovered by mild hydrolysis. Silylation and disilylation reactions did not induce any isomerisation. The structure of these trehalose esters has been determined by using a series of reactions elaborated on synthetic acyl-sugar models. Free hydroxyl groups are transformed into tetrahydropyran ethers, deacylated by dimsyl sodium, methylated and the sugar derivatives are hydrolyzed. The O-methyl-sugars obtained contain a methyl ether group located at the position where the acyl group was present initially. Identification by gas chromatography of the O-methyl-sugars thus allows the location of the fatty acid residues in the glycolipid. It has been demonstrated that no migration occurs. Two types of 6-monomycoloyl-alpha-D-trehalose have been isolated, differing by the nature of the mycolic acid residues. One of them, called MA, contains \"alpha-phlei mycolic acid\". The other one, called MB, contains \"gamma-phlei mycolic acid\" which is the ester of 2-eicosanol with the omega-carboxyl function of a dicarboxylic mycolic acid. Three types of 6,6'-dimycoloyl-alpha-D-trehalose (cord factor) have been obtained. Two of them are symmetrical diesters, containing either two residues of alpha-mycolic acid, or two residues of gamma-mycolic acid. The last one is an unsymmetrical diester, the hydrolysis of which gives one mole of alpha-mycolic acid and one mole of gamma-mycolic acid. The ratio of the different diesters in the cord factor fraction might be explained by some equilibrium between the different 6-ester groups or by a transformation in situ of one species into another one by biochemical modification of the mycolic acid residues."} {"id": "PMID:1261562", "title": "Incorporation of inorganic sulfate in rat-liver Golgi.", "content": "Partial subcellular distribution and specifically the incorporation of 35SO4 in the Golgi apparatus of rat liver was studied. The isolated Golgi fraction was placed on a further sucrose gradient for subfraction and in all samples the total incorporated label, the trichloroacetic-acid-soluble and insoluble, and chloroform/methanol-soluble and insoluble amounts of label were measured. Approximately 2.3% of the total injected 35S was found in the liver, of which 2% was localized in the isolated Golgi fraction. Further subfractionation of the Golgi has shown that the majority of the 35S is localized at densities 1.12-1.13 g/cm3 in the gradient. In the isolated Golgi fraction 85% of the label was present in the trichloroacetic-acid-soluble and 15% in the insoluble part. Approximately 1% of the label in the Golgi fraction was soluble in chloroform/methanol. On the bases of radioactivity per weight of protein and total radioactivity, the Golgi fractions had the highest activity, except the first supernatant which had higher radioactivity. Briefly, a significant amount of the 35SO4 can be found in the isolated rat liver Golgi 15 min after the injection of the label, and the majority of this label is localized in the material sedimenting at density 1.12-1.13 g/cm3 after subfractionation of the Golgi apparatus.", "contents": "Incorporation of inorganic sulfate in rat-liver Golgi. Partial subcellular distribution and specifically the incorporation of 35SO4 in the Golgi apparatus of rat liver was studied. The isolated Golgi fraction was placed on a further sucrose gradient for subfraction and in all samples the total incorporated label, the trichloroacetic-acid-soluble and insoluble, and chloroform/methanol-soluble and insoluble amounts of label were measured. Approximately 2.3% of the total injected 35S was found in the liver, of which 2% was localized in the isolated Golgi fraction. Further subfractionation of the Golgi has shown that the majority of the 35S is localized at densities 1.12-1.13 g/cm3 in the gradient. In the isolated Golgi fraction 85% of the label was present in the trichloroacetic-acid-soluble and 15% in the insoluble part. Approximately 1% of the label in the Golgi fraction was soluble in chloroform/methanol. On the bases of radioactivity per weight of protein and total radioactivity, the Golgi fractions had the highest activity, except the first supernatant which had higher radioactivity. Briefly, a significant amount of the 35SO4 can be found in the isolated rat liver Golgi 15 min after the injection of the label, and the majority of this label is localized in the material sedimenting at density 1.12-1.13 g/cm3 after subfractionation of the Golgi apparatus."} {"id": "PMID:1261563", "title": "Thermal stability of immobilized enzymes circular dichroism, fluorescence and kinetic measurements of alpha-chymotrypsin attached to soluble carriers.", "content": "The temperature-induced unfolding of alpha-chymotrypsin and of chymotrypsin covalently bound to two soluble transparent carriers, dextran and a copolymer of maleic acid anhydride and acrylic acid, has been studied by tryptophan fluorescence emission, circular dichroic and kinetic measurements. It has been shown that the structural and functional properties of the enzyme when bound to the anionic copolymer are strongly influenced by electrostatic interactions. A number of reference experiments with anionic polyelectrolytes and the hydrogenated monomers of the copolymer suggest that these changes are brought about by the cooperative ion pair formation between protein and polyanionic matrix.", "contents": "Thermal stability of immobilized enzymes circular dichroism, fluorescence and kinetic measurements of alpha-chymotrypsin attached to soluble carriers. The temperature-induced unfolding of alpha-chymotrypsin and of chymotrypsin covalently bound to two soluble transparent carriers, dextran and a copolymer of maleic acid anhydride and acrylic acid, has been studied by tryptophan fluorescence emission, circular dichroic and kinetic measurements. It has been shown that the structural and functional properties of the enzyme when bound to the anionic copolymer are strongly influenced by electrostatic interactions. A number of reference experiments with anionic polyelectrolytes and the hydrogenated monomers of the copolymer suggest that these changes are brought about by the cooperative ion pair formation between protein and polyanionic matrix."} {"id": "PMID:1261564", "title": "Subcellular distribution and properties of poly(A)-containing RNA from cultured plant cells.", "content": "Cultured sycamore cells rapidly incorporate [3H]uridine or [32P]orthophosphate into rRNA precursors and polydisperse RNA. Mature rRNA accumulates only after a lag period of approximately 40 min. Fractionation of pulse-labelled cells and analysis of the RNA shows that after 30 min the rRNA precursors, together with some polydisperse RNA, are confined to the nucleus. In consequence radioactive polydisperse RNA can be isolated from polyribosomes in the complete absence of labelled rRNA. Approximately 40% of this RNA is retained by an oligo(dT)-cellulose column and by this criterion is judged to contain poly(A) sequences. A smaller proportion of nuclear polydisperse RNA also contains poly(A). The tendency for poly(A)-containing RNA to aggregate complicates molecular weight determinations. Denaturation of poly(A)-containing RNA in 8 M urea prior to gel electrophoresis produces a broad peak of RNA with an average Mr = 10(6). Analysis of the nucleotide composition of total cell poly(A)-containing RNA shows that it contains 41% AMP. Roughly 6% of this RNA is resistant to digestion by ribonuclease A and T1. AMP is the only nucleotide detectable in these fragments. From their mobility during electrophoresis in 8 M urea at 60 degrees C with 5.8-S, 5-S and tRNA as molecular weight markers it is concluded that the poly(A) regions contain an average of 160 nucleotides.", "contents": "Subcellular distribution and properties of poly(A)-containing RNA from cultured plant cells. Cultured sycamore cells rapidly incorporate [3H]uridine or [32P]orthophosphate into rRNA precursors and polydisperse RNA. Mature rRNA accumulates only after a lag period of approximately 40 min. Fractionation of pulse-labelled cells and analysis of the RNA shows that after 30 min the rRNA precursors, together with some polydisperse RNA, are confined to the nucleus. In consequence radioactive polydisperse RNA can be isolated from polyribosomes in the complete absence of labelled rRNA. Approximately 40% of this RNA is retained by an oligo(dT)-cellulose column and by this criterion is judged to contain poly(A) sequences. A smaller proportion of nuclear polydisperse RNA also contains poly(A). The tendency for poly(A)-containing RNA to aggregate complicates molecular weight determinations. Denaturation of poly(A)-containing RNA in 8 M urea prior to gel electrophoresis produces a broad peak of RNA with an average Mr = 10(6). Analysis of the nucleotide composition of total cell poly(A)-containing RNA shows that it contains 41% AMP. Roughly 6% of this RNA is resistant to digestion by ribonuclease A and T1. AMP is the only nucleotide detectable in these fragments. From their mobility during electrophoresis in 8 M urea at 60 degrees C with 5.8-S, 5-S and tRNA as molecular weight markers it is concluded that the poly(A) regions contain an average of 160 nucleotides."} {"id": "PMID:1261565", "title": "Studies of malformation syndromes of man XXXXIA: anatomical studies in the Hanhart syndrome--a pathogenetic hypothesis.", "content": "Two infants with the Hanhart syndrome, i.e. micrognathia, microglossia, terminal deficiency of all limbs and imperforate anus in one, were dissected and studied in detail. The interrelationships of the muscular and skeletal defects suggested that they were the result of incomplete rather than abnormal morphogenesis. We speculate that the oral and limb abnormalities resulted from deficient mesodermal proliferation caused by disturbances in the ectodermal-mesodermal interactions beginning about the 4th week of development. The imperforate anus may also relate to the proposed defect.", "contents": "Studies of malformation syndromes of man XXXXIA: anatomical studies in the Hanhart syndrome--a pathogenetic hypothesis. Two infants with the Hanhart syndrome, i.e. micrognathia, microglossia, terminal deficiency of all limbs and imperforate anus in one, were dissected and studied in detail. The interrelationships of the muscular and skeletal defects suggested that they were the result of incomplete rather than abnormal morphogenesis. We speculate that the oral and limb abnormalities resulted from deficient mesodermal proliferation caused by disturbances in the ectodermal-mesodermal interactions beginning about the 4th week of development. The imperforate anus may also relate to the proposed defect."} {"id": "PMID:1261566", "title": "Studies of malformation syndromes of man XXXXI B: nosologic studies in the Hanhart and the M\u00f6bius syndrome.", "content": "We reviewed etiologic and phenotypic aspects of those orofacial and limb anomalies usually diagnosed as Hanhart syndrome and Mobius syndrome but also those described, among others, under names such as aglossia-adactylia syndrome, gloss-palatine ankylosis, ankyloglossia superior, peromelia and micrognathia, cleft palate/lateral synechiae syndrome, and the Charlie M. syndrome. By coding the degree of severity of the limb defects it was possible to compare these cases quantitatively and to determine the nosologic significance of associated cranial nerve palsies and chest abnormalities. We analyzed 7 personal and 62 previously reported cases and found: 1. that the severity in the upper limbs and, particularly, malformations of the feet, but not the presence or absence of cranial nerve palsies, is a significant feature in the differentiation of cases, and 2. that the group of patients with cranial nerve palsies includes some with limb defects similar to those in the Hanhart syndrome and others with features which overlap the manifestations of the Poland syndrome. Still other cases had cranial nerve palsy as an isolated trait or as a component manifestation of several different syndromes. These findings permit re-definition and nosologic delimitation of the various syndromes as follows: 1. The Hanhart-syndrome: usually severe limb defect of at least one hand or foot, frequently associated with severe oral abnormalities and sometimes also with cranial nerve palsy. Most cases reported as aglossia-adactylia syndrome, aglossia-hypomelia syndrome, and some cases reported as glossopalatine ankylosis, ankyloglossia superior and Mobius syndrome describe instances of the Hanhart syndrome. 2. The Poland-Mobius syndrome: we suggest this term to refer to those cases of \"Mobius syndrome\" which have a chest defect and/or symbrachydactyly of the type seen in the Poland syndrome. We suspect that these cases of the \"Mobius syndrome,\" and most of the cases which are usually diagnosed as Poland syndrome represent a different spectrum of the same condition, hence the term Poland-Mobius syndrome. 3. The autosomal dominant cleft palate/lateral synechiae syndrome delineated by Fuhrmann et al. and other apparently less frequent conditions are mentioned in the discussion. Cranial nerve palsy obviously occurs in several etiologically distinct conditions. An analogous situation is present, although less obvious, in the Hanhart and the Poland-Mobius syndrome. Both of these conditions are formal genesis malformation syndromes which implies that they are etiologically non-specific developmental field complexes. In the Hanhart syndrome Bersu et al. postulate a common pathogenetic disturbance for oral and limb defects, thus suggesting that the manifestations represent a single anomaly rather than a \"syndrome.\" This anomaly, for which we suggest the term Kettner anomaly, may occur not only in the Hanhart syndrome but also in other conditions. Similarly, the Poland anomaly, i.e...", "contents": "Studies of malformation syndromes of man XXXXI B: nosologic studies in the Hanhart and the M\u00f6bius syndrome. We reviewed etiologic and phenotypic aspects of those orofacial and limb anomalies usually diagnosed as Hanhart syndrome and Mobius syndrome but also those described, among others, under names such as aglossia-adactylia syndrome, gloss-palatine ankylosis, ankyloglossia superior, peromelia and micrognathia, cleft palate/lateral synechiae syndrome, and the Charlie M. syndrome. By coding the degree of severity of the limb defects it was possible to compare these cases quantitatively and to determine the nosologic significance of associated cranial nerve palsies and chest abnormalities. We analyzed 7 personal and 62 previously reported cases and found: 1. that the severity in the upper limbs and, particularly, malformations of the feet, but not the presence or absence of cranial nerve palsies, is a significant feature in the differentiation of cases, and 2. that the group of patients with cranial nerve palsies includes some with limb defects similar to those in the Hanhart syndrome and others with features which overlap the manifestations of the Poland syndrome. Still other cases had cranial nerve palsy as an isolated trait or as a component manifestation of several different syndromes. These findings permit re-definition and nosologic delimitation of the various syndromes as follows: 1. The Hanhart-syndrome: usually severe limb defect of at least one hand or foot, frequently associated with severe oral abnormalities and sometimes also with cranial nerve palsy. Most cases reported as aglossia-adactylia syndrome, aglossia-hypomelia syndrome, and some cases reported as glossopalatine ankylosis, ankyloglossia superior and Mobius syndrome describe instances of the Hanhart syndrome. 2. The Poland-Mobius syndrome: we suggest this term to refer to those cases of \"Mobius syndrome\" which have a chest defect and/or symbrachydactyly of the type seen in the Poland syndrome. We suspect that these cases of the \"Mobius syndrome,\" and most of the cases which are usually diagnosed as Poland syndrome represent a different spectrum of the same condition, hence the term Poland-Mobius syndrome. 3. The autosomal dominant cleft palate/lateral synechiae syndrome delineated by Fuhrmann et al. and other apparently less frequent conditions are mentioned in the discussion. Cranial nerve palsy obviously occurs in several etiologically distinct conditions. An analogous situation is present, although less obvious, in the Hanhart and the Poland-Mobius syndrome. Both of these conditions are formal genesis malformation syndromes which implies that they are etiologically non-specific developmental field complexes. In the Hanhart syndrome Bersu et al. postulate a common pathogenetic disturbance for oral and limb defects, thus suggesting that the manifestations represent a single anomaly rather than a \"syndrome.\" This anomaly, for which we suggest the term Kettner anomaly, may occur not only in the Hanhart syndrome but also in other conditions. Similarly, the Poland anomaly, i.e..."} {"id": "PMID:1261567", "title": "[Lipic content and fatty acid pattern in human milk and cow's milk (author's transl)].", "content": "The lipid content and the fatty acid pattern in human colostrum, transitional and mature molk and in pasteurised cow's milk and in \"Vorzugsmilch\" (special untreated milk) were investigated. The analyses were done in pooled daily milk of 15-20 women to archieve representative mean values for human milk. The lipid content amounted to 1.87 g/100 ml in human colostrum, 2.82 g/100 ml in transitional mild and 3.45 g/100 ml in mature human milk. The increase of lipid content during lactation is attributed to maturation of the milk and is not influenced by maternal diet. During maturation of human milk decreases the portion of the unsaturated fatty acids from 57 to 53%, the portion of saturated fatty acids increases accordingly from 43 to 47%. The decrease of the unsaturated fatty acids is mainly due to the decrease of oleic acid while the portion of linoleic acid increases from 10.8 to 12.0%. In the same duration the linoleic acid portion of the energy content of human milk increases there with from 3.3 keal % in colostrum to 5.6 kcal % in mature human milk. Lipid content and fatty acid pattern of pasteurised cow's milk and \"Vorzugsmilch\" were compared with the corresponding values in human milk. The importance of the differences in lipid content and fatty acid pattern of human milk and cow's milk for the nutrition of healthy young infants is discussed.", "contents": "[Lipic content and fatty acid pattern in human milk and cow's milk (author's transl)]. The lipid content and the fatty acid pattern in human colostrum, transitional and mature molk and in pasteurised cow's milk and in \"Vorzugsmilch\" (special untreated milk) were investigated. The analyses were done in pooled daily milk of 15-20 women to archieve representative mean values for human milk. The lipid content amounted to 1.87 g/100 ml in human colostrum, 2.82 g/100 ml in transitional mild and 3.45 g/100 ml in mature human milk. The increase of lipid content during lactation is attributed to maturation of the milk and is not influenced by maternal diet. During maturation of human milk decreases the portion of the unsaturated fatty acids from 57 to 53%, the portion of saturated fatty acids increases accordingly from 43 to 47%. The decrease of the unsaturated fatty acids is mainly due to the decrease of oleic acid while the portion of linoleic acid increases from 10.8 to 12.0%. In the same duration the linoleic acid portion of the energy content of human milk increases there with from 3.3 keal % in colostrum to 5.6 kcal % in mature human milk. Lipid content and fatty acid pattern of pasteurised cow's milk and \"Vorzugsmilch\" were compared with the corresponding values in human milk. The importance of the differences in lipid content and fatty acid pattern of human milk and cow's milk for the nutrition of healthy young infants is discussed."} {"id": "PMID:1261568", "title": "Acid-base parameters and alveolar-arterial oxygen tension gradients in healthy neonatal and postneonatal infants.", "content": "In a randomly selected group of asymptomatic neonatal and postneonatal infants, acid-base parameters and oxygen tension measurements in arterial blood (radial artery) were carried out during air and oxygen breathing. Acid-base results showed a mild, partially compensated metabolic acidosis, indicating adequate pulmonary function. Arterial oxygen tension was in the normal range for this age group. Calculated alveolar oxygen tension levels demonstrated alveolar-arterial gradients of about 30 mm Hg during air breathing and 320 mm Hg during O2 breathing. Volumes of R-L shunts calculated from these gradients, were in the order of magnitude commonly found at this age, i.e., about 20% of right cardiac output. No differences were discernible between infants of appropriate weight for gestational age and small-for-date infants.", "contents": "Acid-base parameters and alveolar-arterial oxygen tension gradients in healthy neonatal and postneonatal infants. In a randomly selected group of asymptomatic neonatal and postneonatal infants, acid-base parameters and oxygen tension measurements in arterial blood (radial artery) were carried out during air and oxygen breathing. Acid-base results showed a mild, partially compensated metabolic acidosis, indicating adequate pulmonary function. Arterial oxygen tension was in the normal range for this age group. Calculated alveolar oxygen tension levels demonstrated alveolar-arterial gradients of about 30 mm Hg during air breathing and 320 mm Hg during O2 breathing. Volumes of R-L shunts calculated from these gradients, were in the order of magnitude commonly found at this age, i.e., about 20% of right cardiac output. No differences were discernible between infants of appropriate weight for gestational age and small-for-date infants."} {"id": "PMID:1261569", "title": "Repeated circadian growth hormone, luteinizing hormone, and follicle-stimulating hormone in children: influence of 9-alpha-fluorohydrocortisone.", "content": "Growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in plasma of 5 children at different pubertal stages and suffering from moderate orthostatic complaints, were measured by radioimmunoassay (RIA). Parameters for secretory capacity were arginine loading and circadian hormonal patterns in hourly intervals from 8 a.m. to 8 p.m. and in half-hourly intervals from 8 p.m. to 8 a.m. before and after 6 weeks treatment with 9-alpha-fluorohydrocortisone (9-alpha-F, Astonin-H, Fa. Merck, Darmstadt, 0.1--0.2 mg/day. Plasma GH during arginine tests and in circadian levels remained unchanged, but circadian LH showed a consistent slight rise in all children. With pubertal development, magnitude and timing of GH peaks increased in boys, and rather decreased in the two girls toward late puberty. Episodic fluctuation of LH and FSH were more marked during sleep, and increased in the three bosy as puberty advanced. Similar intraindividual patterns for GH and LH, but not for FSH were noted in 4 children. Timing of GH and LH peaks appeared to be correlated. An intrinsic hereditary long-term regulatory principle is discussed.", "contents": "Repeated circadian growth hormone, luteinizing hormone, and follicle-stimulating hormone in children: influence of 9-alpha-fluorohydrocortisone. Growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in plasma of 5 children at different pubertal stages and suffering from moderate orthostatic complaints, were measured by radioimmunoassay (RIA). Parameters for secretory capacity were arginine loading and circadian hormonal patterns in hourly intervals from 8 a.m. to 8 p.m. and in half-hourly intervals from 8 p.m. to 8 a.m. before and after 6 weeks treatment with 9-alpha-fluorohydrocortisone (9-alpha-F, Astonin-H, Fa. Merck, Darmstadt, 0.1--0.2 mg/day. Plasma GH during arginine tests and in circadian levels remained unchanged, but circadian LH showed a consistent slight rise in all children. With pubertal development, magnitude and timing of GH peaks increased in boys, and rather decreased in the two girls toward late puberty. Episodic fluctuation of LH and FSH were more marked during sleep, and increased in the three bosy as puberty advanced. Similar intraindividual patterns for GH and LH, but not for FSH were noted in 4 children. Timing of GH and LH peaks appeared to be correlated. An intrinsic hereditary long-term regulatory principle is discussed."} {"id": "PMID:1261575", "title": "Aorto-pulmonary relationship, arterio-ventricular alignment, and ventricular septal defects in complete transposition of the great arteries.", "content": "A study of the conal anatomy of 36 specimens of complete transposition of the great arteries (TGA) is reported. The aim of the investigation was to verify if the two main anatomic features of the malformation, i.e. abnormal aorto-pulmonary and arterioventricular relationships, were strictly related to the maldevelopment of the conal structures. The findings indicate that in the cases with mitro-pulmonary fibrous continuity, there is a wide variation in subaortic conal development. and no correlation exists between the anterior position of the aorta and the length of the subaortic parietal conus. Therefore, differential conal absorption does not seem to play a role in the presumptive lack of rotation in TGA. TGA presenting with bilateral conus and biventricular pulmonary trunk origin are relatively frequent in this survey, but no correlation was observed between overriding of the pulmonary artery and development of the subpulmonary parietal conus. Consequently, in TGA the morphogenetic process of transfer of the pulmonary artery above the left ventricle does not seem to depend only on the absorption of the subpulomonary parietal conus. Ventricular septal defects (VSDs) in TGA are related frequently to conal pathology, either to some failure in conal septal growth or to malalignment of the normally developed conal and sinusal components of the ventricular septum.", "contents": "Aorto-pulmonary relationship, arterio-ventricular alignment, and ventricular septal defects in complete transposition of the great arteries. A study of the conal anatomy of 36 specimens of complete transposition of the great arteries (TGA) is reported. The aim of the investigation was to verify if the two main anatomic features of the malformation, i.e. abnormal aorto-pulmonary and arterioventricular relationships, were strictly related to the maldevelopment of the conal structures. The findings indicate that in the cases with mitro-pulmonary fibrous continuity, there is a wide variation in subaortic conal development. and no correlation exists between the anterior position of the aorta and the length of the subaortic parietal conus. Therefore, differential conal absorption does not seem to play a role in the presumptive lack of rotation in TGA. TGA presenting with bilateral conus and biventricular pulmonary trunk origin are relatively frequent in this survey, but no correlation was observed between overriding of the pulmonary artery and development of the subpulmonary parietal conus. Consequently, in TGA the morphogenetic process of transfer of the pulmonary artery above the left ventricle does not seem to depend only on the absorption of the subpulomonary parietal conus. Ventricular septal defects (VSDs) in TGA are related frequently to conal pathology, either to some failure in conal septal growth or to malalignment of the normally developed conal and sinusal components of the ventricular septum."} {"id": "PMID:1261576", "title": "Selective aortic root angiography in the hypoplastic left heart syndrome.", "content": "Selective aortic root angiography was performed in 18 patients with the clinical diagnosis of hypoplastic left heart syndrome in order to allow more precise correlation with echocardiography. Aortic valve atresia and severe hypoplasia of the left heart chambers subsequently were substaniated at necropsy in each instance. Wide variation in the size and shape of the aortic root and ascending aorta was demonstrated angiographically in these patients. In some patients, despite aortic valve atresia, the dimensions of the aortic root and sinuses of Valsalva at angiography were almost normal. In addition, this technique allowed the demonstration of primitive vascular communications between the coronary artery and left ventricular cavity in 1 patient (coronary-cameral fistula). The realization that the aortic root may approach nearly normal size in some patients with the hypoplastic left heart syndrome is essential to the echocardiographic diagnosis of this disease and to the differential diagnosis from other cardiac and noncardiac causes of severe neonatal congestive heart failure.", "contents": "Selective aortic root angiography in the hypoplastic left heart syndrome. Selective aortic root angiography was performed in 18 patients with the clinical diagnosis of hypoplastic left heart syndrome in order to allow more precise correlation with echocardiography. Aortic valve atresia and severe hypoplasia of the left heart chambers subsequently were substaniated at necropsy in each instance. Wide variation in the size and shape of the aortic root and ascending aorta was demonstrated angiographically in these patients. In some patients, despite aortic valve atresia, the dimensions of the aortic root and sinuses of Valsalva at angiography were almost normal. In addition, this technique allowed the demonstration of primitive vascular communications between the coronary artery and left ventricular cavity in 1 patient (coronary-cameral fistula). The realization that the aortic root may approach nearly normal size in some patients with the hypoplastic left heart syndrome is essential to the echocardiographic diagnosis of this disease and to the differential diagnosis from other cardiac and noncardiac causes of severe neonatal congestive heart failure."} {"id": "PMID:1261577", "title": "The pulse in patients with atrial fibrillation: its irregularity and inequality.", "content": "In 32 patients with atrial fibrillation the distributions of the R-R intervals and the carotid pulse records were analyzed in an attempt to define and quantify 'irregularity' and 'inequality' of the pulse and its relationship to the mean ventricular rate. Using our definition or irregularity and inequality of the pulse (the percentage scatter around the mean) we arrived at the conclusion that: (1) the same degree of irregularity is maintained with different mean ventricular rates in the range studied by us (digitalis administration had no significant effect on this irregularity (2) the 'inequality' between beats decreases at slower ventricular rates: (3) a relationship with the postextrasystolic potentiation is suggested.", "contents": "The pulse in patients with atrial fibrillation: its irregularity and inequality. In 32 patients with atrial fibrillation the distributions of the R-R intervals and the carotid pulse records were analyzed in an attempt to define and quantify 'irregularity' and 'inequality' of the pulse and its relationship to the mean ventricular rate. Using our definition or irregularity and inequality of the pulse (the percentage scatter around the mean) we arrived at the conclusion that: (1) the same degree of irregularity is maintained with different mean ventricular rates in the range studied by us (digitalis administration had no significant effect on this irregularity (2) the 'inequality' between beats decreases at slower ventricular rates: (3) a relationship with the postextrasystolic potentiation is suggested."} {"id": "PMID:1261578", "title": "An analysis of pulsus alternans in aortic stenosis.", "content": "Pulsus alternans was studied hemodynamically in 5 patients with calcific aortic stenosis. Left ventricular function was assessed by angiographic volume analysis and by force-velocity analysis. All cases showed alternation of max and min dP/dt and kVmax. Inconsistent factors were an alternating left ventricular enddiastolic pressure, alternating left ventricular enddiastolic volume, alternating left ventricular endsystolic volume, ejection fraction, enddiastolic wall stress and wall stiffness. All cases had a high ventricular mass, but the critical value of ventricular mass or the ratio of mass to left ventricular enddiastolic volume were also inconsistent. Pulses alternans is primarily due to alternating contractility.", "contents": "An analysis of pulsus alternans in aortic stenosis. Pulsus alternans was studied hemodynamically in 5 patients with calcific aortic stenosis. Left ventricular function was assessed by angiographic volume analysis and by force-velocity analysis. All cases showed alternation of max and min dP/dt and kVmax. Inconsistent factors were an alternating left ventricular enddiastolic pressure, alternating left ventricular enddiastolic volume, alternating left ventricular endsystolic volume, ejection fraction, enddiastolic wall stress and wall stiffness. All cases had a high ventricular mass, but the critical value of ventricular mass or the ratio of mass to left ventricular enddiastolic volume were also inconsistent. Pulses alternans is primarily due to alternating contractility."} {"id": "PMID:1261579", "title": "The effect of atropine on calculated sinoatrial conduction time in man.", "content": "This study investigates the effect of atropine on the length of the return cycles after premature atrial stimulation in man. On the assumption that sinus node automaticity is not changed by premature depolarization of the sinus node, sinoatrial conduction time (SACT) was calculated from the differences between the length of the return cycles and the spontaneous cycle length. 11 patients were studied before and after the injection of atropine. In all cases atropine caused an increase in heart rate. In 8 patients the return cycles exhibited a typical behavior. In 6 patients without signs of sinus node dysfunction, the mean calculated SACT was 109 msec, whereas 2 patients with a sick sinus syndrome (SSS) had a mean calculated SACT of 190 and 225 msec, respectively. 3 patients with SSS demonstrated an atypical pattern of the postextrasystolic pauses. In 6 patients without sinus node dysfunction, atropine caused a reduction of calculated SACT about 35%. In 2 patients with SSS the reduction was 38 and 49% of the control value, respectively, whereas in the remaining 3 patients with SSS who had an atypical return cycle pattern, a normalization occurred after the administration of atropine. We conclude that, besides its effects on sinus node automaticity, atropine has also a marked effect on sinoatrial conduction, even in patients with the sick sinus syndrome.", "contents": "The effect of atropine on calculated sinoatrial conduction time in man. This study investigates the effect of atropine on the length of the return cycles after premature atrial stimulation in man. On the assumption that sinus node automaticity is not changed by premature depolarization of the sinus node, sinoatrial conduction time (SACT) was calculated from the differences between the length of the return cycles and the spontaneous cycle length. 11 patients were studied before and after the injection of atropine. In all cases atropine caused an increase in heart rate. In 8 patients the return cycles exhibited a typical behavior. In 6 patients without signs of sinus node dysfunction, the mean calculated SACT was 109 msec, whereas 2 patients with a sick sinus syndrome (SSS) had a mean calculated SACT of 190 and 225 msec, respectively. 3 patients with SSS demonstrated an atypical pattern of the postextrasystolic pauses. In 6 patients without sinus node dysfunction, atropine caused a reduction of calculated SACT about 35%. In 2 patients with SSS the reduction was 38 and 49% of the control value, respectively, whereas in the remaining 3 patients with SSS who had an atypical return cycle pattern, a normalization occurred after the administration of atropine. We conclude that, besides its effects on sinus node automaticity, atropine has also a marked effect on sinoatrial conduction, even in patients with the sick sinus syndrome."} {"id": "PMID:1261580", "title": "Clinical setting and prognostic significance of atrial fibrillation complicating acute myocardial infarction.", "content": "Clinical setting, presence and degree of heart failure (HF) of 80 consecutive patients who developed atrial fibrillation (AF) following acute myocardial infarction were compared to that of 620 patients with acute myocardial infarction and sinus rhythm admitted during the same period. 33 of 163 (20%) with initially mild HF developed AF compared to 5 of 74 (7%) with initially severe HF, and 42 of 463 (9%) without HF (P less than 0.01). Patients with mild HF who developed AF had a higher incidence of deterioration of clinical condition (39 vs 14%, P less than 0.005) and a higher mortality rate (52 vs 22%, P less than 0.001) than patients with mild HF and sinus rhythm. The presence of AF influenced neither the development of HF and mortality rate in patients without HF nor the degree of HF and mortality in patients with initially severe HF. Pericarditis was present in 12 of 42 (28%) with AF occurring in the absence of HF, compared to 3 of 38 (8%) with AF and initially mild HF and to 56 of 620 (9%) with sinus rhythm (P less than 0.05). (1) in the absence of HF, AF may be the consequence of pericarditis; (2) in patients with mild HF, AF may be consequence of HF; (3) the contribution of AF to the subsequent clinical course is only of prognostic significance in patients with mild HF.", "contents": "Clinical setting and prognostic significance of atrial fibrillation complicating acute myocardial infarction. Clinical setting, presence and degree of heart failure (HF) of 80 consecutive patients who developed atrial fibrillation (AF) following acute myocardial infarction were compared to that of 620 patients with acute myocardial infarction and sinus rhythm admitted during the same period. 33 of 163 (20%) with initially mild HF developed AF compared to 5 of 74 (7%) with initially severe HF, and 42 of 463 (9%) without HF (P less than 0.01). Patients with mild HF who developed AF had a higher incidence of deterioration of clinical condition (39 vs 14%, P less than 0.005) and a higher mortality rate (52 vs 22%, P less than 0.001) than patients with mild HF and sinus rhythm. The presence of AF influenced neither the development of HF and mortality rate in patients without HF nor the degree of HF and mortality in patients with initially severe HF. Pericarditis was present in 12 of 42 (28%) with AF occurring in the absence of HF, compared to 3 of 38 (8%) with AF and initially mild HF and to 56 of 620 (9%) with sinus rhythm (P less than 0.05). (1) in the absence of HF, AF may be the consequence of pericarditis; (2) in patients with mild HF, AF may be consequence of HF; (3) the contribution of AF to the subsequent clinical course is only of prognostic significance in patients with mild HF."} {"id": "PMID:1261581", "title": "Ventricular arrhythmias prior to discharge after acute myocardial infarction.", "content": "One hundred consecutive patients in sinus rhythm and without routinely prescribed antiarrhythmic therapy were investigated for ventricular ectopic beats (VEB) prior to discharge after an acute myocardial infarction. The registration was performed for three hours during the day, including light exercise, and three hours at night. The overall VEB frequency was 70%. 34% had uniform VEBs, 22% multiform VEB'S, ANd 11% paired VEB'S 2% HAD THE R-on-T phenomenon and 1% ventricular tachycardia (VT). Ventricular irritability was more common in patients discharged after reinfarction, an estimated large infarct, if they had shown VT or ventricular fibrillation in the acute phase or when treated with diuretics only because of heart failure. There was no lowering of the VEB incidence at night, 17 patients having had ventricular arrhythmias at night only. In 5 cases the VEB'S were of a higher degree during exercise than at rest.", "contents": "Ventricular arrhythmias prior to discharge after acute myocardial infarction. One hundred consecutive patients in sinus rhythm and without routinely prescribed antiarrhythmic therapy were investigated for ventricular ectopic beats (VEB) prior to discharge after an acute myocardial infarction. The registration was performed for three hours during the day, including light exercise, and three hours at night. The overall VEB frequency was 70%. 34% had uniform VEBs, 22% multiform VEB'S, ANd 11% paired VEB'S 2% HAD THE R-on-T phenomenon and 1% ventricular tachycardia (VT). Ventricular irritability was more common in patients discharged after reinfarction, an estimated large infarct, if they had shown VT or ventricular fibrillation in the acute phase or when treated with diuretics only because of heart failure. There was no lowering of the VEB incidence at night, 17 patients having had ventricular arrhythmias at night only. In 5 cases the VEB'S were of a higher degree during exercise than at rest."} {"id": "PMID:1261582", "title": "Initial vectors of ventricular premature beats and anterior fascicular conduction defects.", "content": "Vectorcardiographic studies on ventricular premature beats (VPB'S), occurring in records wherein the sinus beats were associated with an intraventricular conduction defect attributed to anterior fascicular delay or block, did not identify the exact site of a presumed reentry mechanism. The hypothesis that the orientation of the initial vectors of the VPB might reveal either anterograde or retrograde emergence from the anterior fasciulus iwth a reentry PVB was not strongly supported, although one or the other mechanism was compatible with the early vectors of certain VPBs. The VPBs revealed greater angular change on the spatial orientation of sequential early vectors (5--10--15 milliseconds) than occurred in sinus beats. Recurring VPBs, which appeared to casual visual inspection steriotyped in form, showed considerable variation in the orientation of the early vectors, indicating, in the cases studied, that VPBs, in the strictest sense, may be associated with differing initial entrance pathways to the myocardium and thus may be 'multiform'.", "contents": "Initial vectors of ventricular premature beats and anterior fascicular conduction defects. Vectorcardiographic studies on ventricular premature beats (VPB'S), occurring in records wherein the sinus beats were associated with an intraventricular conduction defect attributed to anterior fascicular delay or block, did not identify the exact site of a presumed reentry mechanism. The hypothesis that the orientation of the initial vectors of the VPB might reveal either anterograde or retrograde emergence from the anterior fasciulus iwth a reentry PVB was not strongly supported, although one or the other mechanism was compatible with the early vectors of certain VPBs. The VPBs revealed greater angular change on the spatial orientation of sequential early vectors (5--10--15 milliseconds) than occurred in sinus beats. Recurring VPBs, which appeared to casual visual inspection steriotyped in form, showed considerable variation in the orientation of the early vectors, indicating, in the cases studied, that VPBs, in the strictest sense, may be associated with differing initial entrance pathways to the myocardium and thus may be 'multiform'."} {"id": "PMID:1261583", "title": "Hemodynamic effects of verapamil and practolol in man.", "content": "The hemodynamic effects of verapamil and practolol were investigated in a group of 10 selected patients (7 with coronary artery disease) undergoing cardiac catherization. The drugs were given i.v. in a dose of 0.1 mg/kg, alone or in combination, before and after controling the heart rate by atrial pacing. Measured hemodynamic parameters included aortic and left ventricular pressure and its first derivative, cardiac output, and echocardiographically derived left ventricular dimensions. Each drug given individually caused minor hemodynamic changes, but the combination of practolol and verapamil when the heart rate was fixed by atrial pacing invaribly caused a reduction in LV dp/dt max which was independent of preload and afterload. It is concluded that both drugs have a mildly negative inotropic effect when administered at this dose intravenously to patients with normal or mildly impaired left ventricular function. The myocardial depression was more apparent when practolol preceded verpamil. Caution must be exercised when using these drugs in combination in patients with impaired myocardial function.", "contents": "Hemodynamic effects of verapamil and practolol in man. The hemodynamic effects of verapamil and practolol were investigated in a group of 10 selected patients (7 with coronary artery disease) undergoing cardiac catherization. The drugs were given i.v. in a dose of 0.1 mg/kg, alone or in combination, before and after controling the heart rate by atrial pacing. Measured hemodynamic parameters included aortic and left ventricular pressure and its first derivative, cardiac output, and echocardiographically derived left ventricular dimensions. Each drug given individually caused minor hemodynamic changes, but the combination of practolol and verapamil when the heart rate was fixed by atrial pacing invaribly caused a reduction in LV dp/dt max which was independent of preload and afterload. It is concluded that both drugs have a mildly negative inotropic effect when administered at this dose intravenously to patients with normal or mildly impaired left ventricular function. The myocardial depression was more apparent when practolol preceded verpamil. Caution must be exercised when using these drugs in combination in patients with impaired myocardial function."} {"id": "PMID:1261584", "title": "Comparison of verapamil and practolol in paroxysmal supraventricular tachycardia.", "content": "40 patients with paroxysmal supraventricular tachycardia were allocated to two different treatment groups according to their year of birth. Those patients born on odd years were given 5 mg of practolol intravenously, those born on even years receiving 5 mg of verapamil, and if the tachycardia continued, the same injection was repeated after 5 minutes. If practolol treatment failed, the patient was given 5 mg of verapamil half an hour later, and vice versa. Verapamil restored sinus rhythm in 19 patients out of 20. Practolol proved effective in 8 out of 20. In patients who were switched over to the other treatment verapamil was effective in 9 out of 11 and practolol in 1 patient. Side effects were few. Marked hypotension occurred in 2 patients, in 1 patient after 5 mg of verapamil, and after 5 mg of practolol in the other. It is concluded that verapamil is a very effective agent in the treatment of paroxysmal supraventricular tachycardia. Selection of patients is emphasized to increase the safety of its use.", "contents": "Comparison of verapamil and practolol in paroxysmal supraventricular tachycardia. 40 patients with paroxysmal supraventricular tachycardia were allocated to two different treatment groups according to their year of birth. Those patients born on odd years were given 5 mg of practolol intravenously, those born on even years receiving 5 mg of verapamil, and if the tachycardia continued, the same injection was repeated after 5 minutes. If practolol treatment failed, the patient was given 5 mg of verapamil half an hour later, and vice versa. Verapamil restored sinus rhythm in 19 patients out of 20. Practolol proved effective in 8 out of 20. In patients who were switched over to the other treatment verapamil was effective in 9 out of 11 and practolol in 1 patient. Side effects were few. Marked hypotension occurred in 2 patients, in 1 patient after 5 mg of verapamil, and after 5 mg of practolol in the other. It is concluded that verapamil is a very effective agent in the treatment of paroxysmal supraventricular tachycardia. Selection of patients is emphasized to increase the safety of its use."} {"id": "PMID:1261585", "title": "Triglyceride metabolism in acute starvation: the role of secretin and glucagon.", "content": "Plasma lipid and hormone levels have been measured during 72 hours total starvation in nine healthy subjects, to assess the relative importance of hormones and substrates in human triglyceride metabolism. Plasma free fatty acid and glycerol concentrations rose steadily on each day of starvation. Plasma triglyceride concentrations rose on the second and third days, from a control level of 649 +/- 67 mg/1 to a maximum of 1001 +/- 66 mg/1. Plasma cholesterol concentrations remained unchanged while glucose concentrations fell and insulin did not change. Plasma glucagon (C-GLI) levels doubled while secretin levels, reported previously, rose threefold. It is suggested that during acute starvation the rise in triglyceride concentration results from the increased availability of free fatty acids, and that elevated secretin and glucagon levels enhance lipolysis and hence provide substrates for triglyceride synthesis.", "contents": "Triglyceride metabolism in acute starvation: the role of secretin and glucagon. Plasma lipid and hormone levels have been measured during 72 hours total starvation in nine healthy subjects, to assess the relative importance of hormones and substrates in human triglyceride metabolism. Plasma free fatty acid and glycerol concentrations rose steadily on each day of starvation. Plasma triglyceride concentrations rose on the second and third days, from a control level of 649 +/- 67 mg/1 to a maximum of 1001 +/- 66 mg/1. Plasma cholesterol concentrations remained unchanged while glucose concentrations fell and insulin did not change. Plasma glucagon (C-GLI) levels doubled while secretin levels, reported previously, rose threefold. It is suggested that during acute starvation the rise in triglyceride concentration results from the increased availability of free fatty acids, and that elevated secretin and glucagon levels enhance lipolysis and hence provide substrates for triglyceride synthesis."} {"id": "PMID:1261586", "title": "Influence of ureteral catheter size on urinary flow rate and glomerular filtration rate in the rat.", "content": "The influence of ureteral catheter diameter on renal function was studied in rats during different diuretic states. Urinary flow rate and glomerular filtration rate were measured on each rat using ureteral catheters of two different internal diameters. In non-diuretic rats, urinary flow rate and glomerular filtration rate did not change according to the catheter diameter. In diuretic rats, urinary flow rate was from 40 to 70% lower with the smaller catheter. Differences became more marked as urinary flow rate increased. Glomerular filtration rates were about 20% lower when measured with small catheters. These results clearly demonstrate that the use of small diameter ureteral catheters during diuretic states leads to a decrease in glomerular filtration rate and urinary flow rate. The results also emphasize the importance of using large diameter catheters during such experimental conditions.", "contents": "Influence of ureteral catheter size on urinary flow rate and glomerular filtration rate in the rat. The influence of ureteral catheter diameter on renal function was studied in rats during different diuretic states. Urinary flow rate and glomerular filtration rate were measured on each rat using ureteral catheters of two different internal diameters. In non-diuretic rats, urinary flow rate and glomerular filtration rate did not change according to the catheter diameter. In diuretic rats, urinary flow rate was from 40 to 70% lower with the smaller catheter. Differences became more marked as urinary flow rate increased. Glomerular filtration rates were about 20% lower when measured with small catheters. These results clearly demonstrate that the use of small diameter ureteral catheters during diuretic states leads to a decrease in glomerular filtration rate and urinary flow rate. The results also emphasize the importance of using large diameter catheters during such experimental conditions."} {"id": "PMID:1261587", "title": "Renin-aldosterone axis in ethanol intoxication and hangover.", "content": "The renin-aldosterone system was studied in human volunteers during ethanol intoxication and hangover. Plasma renin activity increased more than 100%, when 1.5 - 2.3 g ethanol per kg body weight was ingested over a three hour period. During hangover the increase even exceeded 200%. Plasma aldosterone concentration decreased during ethanol intoxication, but increased greatly during hangover. It is suggested that the stimulation of the renin-aldosterone axis during ethanol intoxication and hangover is due to dehydration and increased activity of the sympathetic nervous system.", "contents": "Renin-aldosterone axis in ethanol intoxication and hangover. The renin-aldosterone system was studied in human volunteers during ethanol intoxication and hangover. Plasma renin activity increased more than 100%, when 1.5 - 2.3 g ethanol per kg body weight was ingested over a three hour period. During hangover the increase even exceeded 200%. Plasma aldosterone concentration decreased during ethanol intoxication, but increased greatly during hangover. It is suggested that the stimulation of the renin-aldosterone axis during ethanol intoxication and hangover is due to dehydration and increased activity of the sympathetic nervous system."} {"id": "PMID:1261588", "title": "On the mechanism of the coronary dilator effect of serotonin in the dog.", "content": "In experiments designed to determine the nature of the coronary dilator effect of serotonin the influence of intracoronary administration of the amine on coronary perfusion pressure, heart rate and ventricular contractile force was assessed in anesthetized open-chest dogs in which the left coronary artery was perfused with blood at a constant rate. Serotonin elicited dose-related decreases in coronary perfusion pressure and increases in contractile force, and lowered heart rate slightly. The dilator response was antagonized by methysergide, slightly potentiated by practolol and unaffected by reserpine. The inotropic effect was partially antagonized by methysergide and completely blocked by practolol and reserpine. It is concluded that serotonin induces coronary dilatation by direct stimulation of specific receptors that this effect is independent of the cardiac stimulation produced by the amine, and the latter response is mediated through beta1-adrenoceptors activated by released norepinephrine.", "contents": "On the mechanism of the coronary dilator effect of serotonin in the dog. In experiments designed to determine the nature of the coronary dilator effect of serotonin the influence of intracoronary administration of the amine on coronary perfusion pressure, heart rate and ventricular contractile force was assessed in anesthetized open-chest dogs in which the left coronary artery was perfused with blood at a constant rate. Serotonin elicited dose-related decreases in coronary perfusion pressure and increases in contractile force, and lowered heart rate slightly. The dilator response was antagonized by methysergide, slightly potentiated by practolol and unaffected by reserpine. The inotropic effect was partially antagonized by methysergide and completely blocked by practolol and reserpine. It is concluded that serotonin induces coronary dilatation by direct stimulation of specific receptors that this effect is independent of the cardiac stimulation produced by the amine, and the latter response is mediated through beta1-adrenoceptors activated by released norepinephrine."} {"id": "PMID:1261589", "title": "Bronchopulmonary pharmacology of some prostaglandin endoperoxide analogs in the dog.", "content": "This investigation examined quantitatively the bronchopulmonary effects of two prostaglandin endoperoxide analogs (cyclic ethers) in the spontaneously breathing, anesthetized dog. Responses to these agents were measured by computer analyses and compared to those produced by prostaglandin F2alpha (PGF2alpha). In a dose range of 0.03-1.0 mug/kg i.v., both cyclic ethers produced dose-related alterations in pulmonary airway resistance dynamic lung compliance, expiratory airflow rate, tidal volume and respiratory frequency. These pulmonary changes were significantly greater than those observed for PGF2alpha (0.3-3.0 mug/kg). The onset of activity was prompt (less than 1 min) and recovery was complete within 5-10 min. Atropine pretreatment greatly reduced the airway resistance effects of all three test agents, thus suggesting some cholinergic component to their potent bronchoconstrictor activities. These cyclic ethers are stable forms of prostaglandin endoperoxides and may represent invaluable pharmacologic tools for the further study of intermediates in prostaglandin synthesis.", "contents": "Bronchopulmonary pharmacology of some prostaglandin endoperoxide analogs in the dog. This investigation examined quantitatively the bronchopulmonary effects of two prostaglandin endoperoxide analogs (cyclic ethers) in the spontaneously breathing, anesthetized dog. Responses to these agents were measured by computer analyses and compared to those produced by prostaglandin F2alpha (PGF2alpha). In a dose range of 0.03-1.0 mug/kg i.v., both cyclic ethers produced dose-related alterations in pulmonary airway resistance dynamic lung compliance, expiratory airflow rate, tidal volume and respiratory frequency. These pulmonary changes were significantly greater than those observed for PGF2alpha (0.3-3.0 mug/kg). The onset of activity was prompt (less than 1 min) and recovery was complete within 5-10 min. Atropine pretreatment greatly reduced the airway resistance effects of all three test agents, thus suggesting some cholinergic component to their potent bronchoconstrictor activities. These cyclic ethers are stable forms of prostaglandin endoperoxides and may represent invaluable pharmacologic tools for the further study of intermediates in prostaglandin synthesis."} {"id": "PMID:1261590", "title": "Comparative effects of four migraine prophylactic drugs on an isolated extracranial artery.", "content": "Clonidine and methysergide constrict the rabbit auricular artery by activating smooth muscle alpha-adrenoceptors. Clonidine inhibits and methysergide enhances responses to stimulation of the sympathetic nerves. Both drugs sensitise the artery to a variety of vasoconstrictor stimuli, although not to potassium chloride. This weak generalised sensitisation may depend on clonidine and methysergide themselves being vasoconstrictor since sensitisation after clonidine did not occur when vasoconstriction was abolished with phentolamine. The marked potentiation of 5-HT and tryptamine observed during clonidine perfusion may reflect a property of the tryptamines since it was observed during perfusion with histamine but not when histamine vasoconstriction was abolished with mepyramine. Cyproheptadine and pizotifen neither constrict the artery nor sensitise it to vasoconstrictor agents. They inhibit responses to nerve stimulation, alpha-adrenoceptor agonists, potassium chloride and particularly histamine. Sensitisation of blood vessels reinforced by direct vasoconstriction may contribute to the mechanism of action of clonidine and methysergide in migraine. Conversely, alterations in vascular function may be less important to the antimigraine actions of either cyproheptadine or pizotifen.", "contents": "Comparative effects of four migraine prophylactic drugs on an isolated extracranial artery. Clonidine and methysergide constrict the rabbit auricular artery by activating smooth muscle alpha-adrenoceptors. Clonidine inhibits and methysergide enhances responses to stimulation of the sympathetic nerves. Both drugs sensitise the artery to a variety of vasoconstrictor stimuli, although not to potassium chloride. This weak generalised sensitisation may depend on clonidine and methysergide themselves being vasoconstrictor since sensitisation after clonidine did not occur when vasoconstriction was abolished with phentolamine. The marked potentiation of 5-HT and tryptamine observed during clonidine perfusion may reflect a property of the tryptamines since it was observed during perfusion with histamine but not when histamine vasoconstriction was abolished with mepyramine. Cyproheptadine and pizotifen neither constrict the artery nor sensitise it to vasoconstrictor agents. They inhibit responses to nerve stimulation, alpha-adrenoceptor agonists, potassium chloride and particularly histamine. Sensitisation of blood vessels reinforced by direct vasoconstriction may contribute to the mechanism of action of clonidine and methysergide in migraine. Conversely, alterations in vascular function may be less important to the antimigraine actions of either cyproheptadine or pizotifen."} {"id": "PMID:1261591", "title": "Antiarrhythmic and hemodynamic effects of an aminosteroid (Org 3001) in the digitalized dog.", "content": "Org 6001 (3alpha-amino-5alpha-androstan-2beta-ol-17-one-hydrochloride) is an orally non-hormonal aminosteroid possessing antiarrhythmic activity. In 13 dogs the efficacy of the drug against ouabain-induced ventricular tachycardia (VT) was studied. VT was produced by a mean dose of 67.5 +/- 18.7 mug/kg ouabain, administered by continuous infusion of 25 mug/min. 20 min after the onset of VT an 0.125 mg/kg/min infusion of Org 6001 was initiated, doubling the dose every 10 min. In all dogs VT was reverted into normal sinus rhythm (NSR) by a dose of 9.72 +/- 7.07 mg/kg (0.87-20.75 mg/kg) Org 6001. The duration of VT ranged from 27-61 min (mean 47.1 +/- 11.4 min), including the 20 min waiting period. NSR persisted in 8 dogs until the experiment was terminated (90 min after onset of VT), while in 5 dogs VT returned after 3-23 min sufficient to revert VT into NSR. A bolus injection of Org 6001 (10 mg/kg) gave an immediate return to NSR in 3 dogs, in which VT was provoked again by administration of a second dose of ouabain after the 90 min period had elapsed. Though the interaction of ouabain makes a quantitative analysis of the negative inotropic effects difficult, it appeared that there uas no major hemodynamic deterioration during and after treatment with Org 6001. During digitalization there was a significant increase in the first derivative of left ventricular systolic pressure (peak LVdP/dt) from 2340 +/- 600 to 3650 +/- 1070 mm Hg/sec and in peripheral resistance, while heart rate decreased. During VT, left ventricular systolic pressure (LVSP) and mean aortic pressure (MAP) dropped by approximately 20 mm Hg, while heart rate increased significantly. After treatment with Org 6001, LVSP and MAP further decreased to 128 +/- 30 mm Hg (p less than 0.05) areased to 128 +/- 30 mm Hg (p less than 0.05) and 112 +/- 20 mm Hg respectively. Peak LVdP/dt fell from 3650 +/- 1390 to 2780 +/- 970 mm Hg/sec (p less than 0.05). Heart rate had dropped to 126 +/- 22 beats/min (p less than 0.05). During the first 30 min after Org 6001 infusion was stopped none of the parameters showed significant changes, although peak LVdP/dt rose slightly. It is shown in the present investigation that Org 6001 has effective antiarrhythmic properties in controlling ouabain-induced VT with acceptable cardiodepressant actions.", "contents": "Antiarrhythmic and hemodynamic effects of an aminosteroid (Org 3001) in the digitalized dog. Org 6001 (3alpha-amino-5alpha-androstan-2beta-ol-17-one-hydrochloride) is an orally non-hormonal aminosteroid possessing antiarrhythmic activity. In 13 dogs the efficacy of the drug against ouabain-induced ventricular tachycardia (VT) was studied. VT was produced by a mean dose of 67.5 +/- 18.7 mug/kg ouabain, administered by continuous infusion of 25 mug/min. 20 min after the onset of VT an 0.125 mg/kg/min infusion of Org 6001 was initiated, doubling the dose every 10 min. In all dogs VT was reverted into normal sinus rhythm (NSR) by a dose of 9.72 +/- 7.07 mg/kg (0.87-20.75 mg/kg) Org 6001. The duration of VT ranged from 27-61 min (mean 47.1 +/- 11.4 min), including the 20 min waiting period. NSR persisted in 8 dogs until the experiment was terminated (90 min after onset of VT), while in 5 dogs VT returned after 3-23 min sufficient to revert VT into NSR. A bolus injection of Org 6001 (10 mg/kg) gave an immediate return to NSR in 3 dogs, in which VT was provoked again by administration of a second dose of ouabain after the 90 min period had elapsed. Though the interaction of ouabain makes a quantitative analysis of the negative inotropic effects difficult, it appeared that there uas no major hemodynamic deterioration during and after treatment with Org 6001. During digitalization there was a significant increase in the first derivative of left ventricular systolic pressure (peak LVdP/dt) from 2340 +/- 600 to 3650 +/- 1070 mm Hg/sec and in peripheral resistance, while heart rate decreased. During VT, left ventricular systolic pressure (LVSP) and mean aortic pressure (MAP) dropped by approximately 20 mm Hg, while heart rate increased significantly. After treatment with Org 6001, LVSP and MAP further decreased to 128 +/- 30 mm Hg (p less than 0.05) areased to 128 +/- 30 mm Hg (p less than 0.05) and 112 +/- 20 mm Hg respectively. Peak LVdP/dt fell from 3650 +/- 1390 to 2780 +/- 970 mm Hg/sec (p less than 0.05). Heart rate had dropped to 126 +/- 22 beats/min (p less than 0.05). During the first 30 min after Org 6001 infusion was stopped none of the parameters showed significant changes, although peak LVdP/dt rose slightly. It is shown in the present investigation that Org 6001 has effective antiarrhythmic properties in controlling ouabain-induced VT with acceptable cardiodepressant actions."} {"id": "PMID:1261592", "title": "Time-course effects of oral guanethidine administration on cardiovascular and autonomic effects on dogs.", "content": "The time-course effects of guanethidine (2.5 mb/kg/day, p.o.) administered for 2 days, 7 days and 7-8 months were investigated in dogs. Guanethidine treatment for 2 days failed to produce any significant alterations in sympathetic neuronal activity to the myocardium, resting neurogenic tone in the perfused hind limb vasculature and lumbar sympathetic neuronal transmission. Following guanethidine administration for a peroid of 7 days both cardiac and lumbar sympathetic neuronal activity was markedly and significantly depressed with concomitant reduction in heart rate and resting neurogenic tone to the hind limb. However, continued treatment with guanethidine for a period of 7-8 months resulted in complete restoration of cardiac as well as lumbar sympathetic neuronal activity. Both heart rate and resting neurogenic tone were also returned to placebo levels. The development of tolerance of these sympathetic nerves to guanethidine treatment was not associated with any alterations in the activity of adrenergic receptors. Further, there was a significant and time-dependent increase in cholinergic vasocilator activity in the lumbar sympathetic chain which could account for the exertional hypotension noted in the patients receiving guanethidine treatment.", "contents": "Time-course effects of oral guanethidine administration on cardiovascular and autonomic effects on dogs. The time-course effects of guanethidine (2.5 mb/kg/day, p.o.) administered for 2 days, 7 days and 7-8 months were investigated in dogs. Guanethidine treatment for 2 days failed to produce any significant alterations in sympathetic neuronal activity to the myocardium, resting neurogenic tone in the perfused hind limb vasculature and lumbar sympathetic neuronal transmission. Following guanethidine administration for a peroid of 7 days both cardiac and lumbar sympathetic neuronal activity was markedly and significantly depressed with concomitant reduction in heart rate and resting neurogenic tone to the hind limb. However, continued treatment with guanethidine for a period of 7-8 months resulted in complete restoration of cardiac as well as lumbar sympathetic neuronal activity. Both heart rate and resting neurogenic tone were also returned to placebo levels. The development of tolerance of these sympathetic nerves to guanethidine treatment was not associated with any alterations in the activity of adrenergic receptors. Further, there was a significant and time-dependent increase in cholinergic vasocilator activity in the lumbar sympathetic chain which could account for the exertional hypotension noted in the patients receiving guanethidine treatment."} {"id": "PMID:1261593", "title": "Pharmacological comparison of R(+), S(-) and racemic thiopentone in mice.", "content": "The i.p. LD50's of the enantiomorphs of thiopentone have the following increasing order of lethality R(+), racemate and S(-). Whereas the racemate and the S(-) compound have similar therapeutic indices, the R(+) compound has the highest value. The S(-) isomer is the most potent anesthetic agent, followed by the R(+) and the racemate. In the ability to block pentylenetetrazol- and strychnine-induced seizures, the compounds are ranked in the following order of decreased potency: S(-), racemate and R(+). The differences in potency between antipodes have been related to absolute steric configuration of the molecules. Differences in potency of the stereoisomers have been discussed in relationship to known metabolic conversions of thiopentone and its rapid penetration into body fat depots.", "contents": "Pharmacological comparison of R(+), S(-) and racemic thiopentone in mice. The i.p. LD50's of the enantiomorphs of thiopentone have the following increasing order of lethality R(+), racemate and S(-). Whereas the racemate and the S(-) compound have similar therapeutic indices, the R(+) compound has the highest value. The S(-) isomer is the most potent anesthetic agent, followed by the R(+) and the racemate. In the ability to block pentylenetetrazol- and strychnine-induced seizures, the compounds are ranked in the following order of decreased potency: S(-), racemate and R(+). The differences in potency between antipodes have been related to absolute steric configuration of the molecules. Differences in potency of the stereoisomers have been discussed in relationship to known metabolic conversions of thiopentone and its rapid penetration into body fat depots."} {"id": "PMID:1261594", "title": "Frequency dependence of the alpha-adrenoceptor-mediated positive inotropic effect in guinea pig heart.", "content": "Evidence for the role of alpha-adrenoceptors in the production of a positive inotropic effect has been obtained chiefly in heart preparations stimulated at a low rate (1 or 1.4 Hz). However, our previous results suggested that the alpha-receptor-mediated positive inotropic effect could be frequency dependent. In the present study cumulative concentration-inotropic effect curves were obtained in guinea pig ventricle strips treated with adrenaline and stimulated at 1 and at 2.5 Hz. Phentolamine (3 X 10(-6) M) and practolol (10(-6) M) were employed as antagonists. Phentolamine antagonized the effect of low concentrations of adrenaline (10(-9)-10(-8) M) in preparations driven at 1 Hz, but did not modify the curve of the agonist at the higher stimulation rate. In preparations driven at 1 Hz, practolol antagonized the effect of adrenaline at concentration above 3 X 10(-8) M without affecting the curve at lower concentrations, the beta-blocker competitively anatagonized the effect of the agonist at 2.5 Hz. It was concluded that a shortening of the interval between beats abolishes the alpha-mediated positive inotropic effect.", "contents": "Frequency dependence of the alpha-adrenoceptor-mediated positive inotropic effect in guinea pig heart. Evidence for the role of alpha-adrenoceptors in the production of a positive inotropic effect has been obtained chiefly in heart preparations stimulated at a low rate (1 or 1.4 Hz). However, our previous results suggested that the alpha-receptor-mediated positive inotropic effect could be frequency dependent. In the present study cumulative concentration-inotropic effect curves were obtained in guinea pig ventricle strips treated with adrenaline and stimulated at 1 and at 2.5 Hz. Phentolamine (3 X 10(-6) M) and practolol (10(-6) M) were employed as antagonists. Phentolamine antagonized the effect of low concentrations of adrenaline (10(-9)-10(-8) M) in preparations driven at 1 Hz, but did not modify the curve of the agonist at the higher stimulation rate. In preparations driven at 1 Hz, practolol antagonized the effect of adrenaline at concentration above 3 X 10(-8) M without affecting the curve at lower concentrations, the beta-blocker competitively anatagonized the effect of the agonist at 2.5 Hz. It was concluded that a shortening of the interval between beats abolishes the alpha-mediated positive inotropic effect."} {"id": "PMID:1261595", "title": "Study of the laxative properties of the disodium salt of the sulfuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone (DAN-603 in the rat.", "content": "The influence of DAN-603 (disodium salt of sulphuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone) on the propulsive motility of the rat digestive tract was studied by means of indicators (charcoal and pyrvinium pamoate) and radioactive tracers (133BaSO4). The results showed that DAN-603 increases selectively the colon motility without modifying the speed of gastric, intestinal (small intestine) and caecal emptying.", "contents": "Study of the laxative properties of the disodium salt of the sulfuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone (DAN-603 in the rat. The influence of DAN-603 (disodium salt of sulphuric diester of 3,3-bis-(4-hydroxyphenyl)-7-methyl-2-indolinone) on the propulsive motility of the rat digestive tract was studied by means of indicators (charcoal and pyrvinium pamoate) and radioactive tracers (133BaSO4). The results showed that DAN-603 increases selectively the colon motility without modifying the speed of gastric, intestinal (small intestine) and caecal emptying."} {"id": "PMID:1261596", "title": "Butyrophenone influences on the opiate receptor.", "content": "Interaction of neuroleptic drugs with the opiate receptors was investigated by inhibition of the stereospecific binding of 3H-naloxone. Benperidol and pimozide, with IC50's of 0.3-0.5 muM, were more potent than the classical opiates meperidine and propoxyphene. A systematic structure-activity relationship was evident with the basic opiate structure of a benzene and a piperidine ring preserved in active compounds. No correlation between neuroleptic activity and binding to the opiate receptor was demonstrated.", "contents": "Butyrophenone influences on the opiate receptor. Interaction of neuroleptic drugs with the opiate receptors was investigated by inhibition of the stereospecific binding of 3H-naloxone. Benperidol and pimozide, with IC50's of 0.3-0.5 muM, were more potent than the classical opiates meperidine and propoxyphene. A systematic structure-activity relationship was evident with the basic opiate structure of a benzene and a piperidine ring preserved in active compounds. No correlation between neuroleptic activity and binding to the opiate receptor was demonstrated."} {"id": "PMID:1261597", "title": "Effect of metiamide, a histamine H2 - receptor antagonist, on the development of gastric stress ulcers and acid secretion.", "content": "In normal and stressed rats with chronic gastric fistula small doses of metiamide (0.001-0.01 muM/kg) increased and doses of over 20 muM/kg decreased gastric acid secretion. In both these dose ranges of dosage metiamide suppressed the development of stress ulcers, most markedly in doses of 0.005 and 100 muM/kg. Intermediate doses had no such action. Only the anti-ulcer action of large doses of metiamide ran parallel to a reduction in acid secretion. Small doses of metiamide increased gastric secretion, but like larger doses, had a weak adrenergic action.", "contents": "Effect of metiamide, a histamine H2 - receptor antagonist, on the development of gastric stress ulcers and acid secretion. In normal and stressed rats with chronic gastric fistula small doses of metiamide (0.001-0.01 muM/kg) increased and doses of over 20 muM/kg decreased gastric acid secretion. In both these dose ranges of dosage metiamide suppressed the development of stress ulcers, most markedly in doses of 0.005 and 100 muM/kg. Intermediate doses had no such action. Only the anti-ulcer action of large doses of metiamide ran parallel to a reduction in acid secretion. Small doses of metiamide increased gastric secretion, but like larger doses, had a weak adrenergic action."} {"id": "PMID:1261598", "title": "Differential sensitivity to apomorphine and clonidine following frontal cortical damage in rats.", "content": "Rats trained to bar-press on a FI 15 sec schedule for water reinforcement were administered various doses of apomorphine (0.25-10 mg/kg) and clonidine (0.002-0.1 mg/kg) both before and 6-10 weeks after bilateral ablation of frontal cortex. Both drugs monotonically depressed response rates with increasing dose. Frontal cortical lesions increased sensitivity to apomorphine without altering sensitivity to clonidine. The results suggest that the frontal cortex modulates the activity of dopaminergic but not noradrenergic neuronal pathways.", "contents": "Differential sensitivity to apomorphine and clonidine following frontal cortical damage in rats. Rats trained to bar-press on a FI 15 sec schedule for water reinforcement were administered various doses of apomorphine (0.25-10 mg/kg) and clonidine (0.002-0.1 mg/kg) both before and 6-10 weeks after bilateral ablation of frontal cortex. Both drugs monotonically depressed response rates with increasing dose. Frontal cortical lesions increased sensitivity to apomorphine without altering sensitivity to clonidine. The results suggest that the frontal cortex modulates the activity of dopaminergic but not noradrenergic neuronal pathways."} {"id": "PMID:1261599", "title": "Interaction between lanthanum and calcium in isolated guinea-pig heart.", "content": "The effect of lanthanum ion on the contraction of the perfused guinea-pig heart has been investigated. Lanthanum caused inhibition of the contractile force. The dose-response curves suggest that there is more than one site with which lanthanum may interact. The high affinity interaction is antagonised by high external calcium. The possibility that a low concentration of lanthanum may block calcium entry into the myocardium is discussed.", "contents": "Interaction between lanthanum and calcium in isolated guinea-pig heart. The effect of lanthanum ion on the contraction of the perfused guinea-pig heart has been investigated. Lanthanum caused inhibition of the contractile force. The dose-response curves suggest that there is more than one site with which lanthanum may interact. The high affinity interaction is antagonised by high external calcium. The possibility that a low concentration of lanthanum may block calcium entry into the myocardium is discussed."} {"id": "PMID:1261600", "title": "Central hypertensive action of histamine in conscious normotensive cats.", "content": "In conscious normotensive cats intraventricular (i.c.v.) administration of histamine (2.0-50.0 mug) induced dose-related rises in blood pressure, with no increase in heart rate. The hypertensive response elicited by a sub-maximal dose of histamine (10.0 mu i.c.v.) was significantly antagonised by central pretreatment with the H1-receptor antagonist mepyramine maleate (200 mug i.c.v.) but not by the H2-receptor antagonist metiamide hydrochloride (1.0 mg i.c.v.). Behavioural responses were obtained in response to to histamine (10.0 and 50.0 mug i.c.v.), which were not antagonised by these antihistamine pretreatments.", "contents": "Central hypertensive action of histamine in conscious normotensive cats. In conscious normotensive cats intraventricular (i.c.v.) administration of histamine (2.0-50.0 mug) induced dose-related rises in blood pressure, with no increase in heart rate. The hypertensive response elicited by a sub-maximal dose of histamine (10.0 mu i.c.v.) was significantly antagonised by central pretreatment with the H1-receptor antagonist mepyramine maleate (200 mug i.c.v.) but not by the H2-receptor antagonist metiamide hydrochloride (1.0 mg i.c.v.). Behavioural responses were obtained in response to to histamine (10.0 and 50.0 mug i.c.v.), which were not antagonised by these antihistamine pretreatments."} {"id": "PMID:1261601", "title": "Morphine hyperthermia in the rat: an action on the central thermostats.", "content": "The mechanism underlying the hyperthermic response to low doses of morphine has been investigated in rats. Doses of morphine sulfate less than 10 mg/kg i.p. caused a rise in body temperature accompanied by vasoconstriction of the cutaneous blood vessels of the tail. This hyperthermia, unlike the hypothermia following higher doses of morphine was not blocked by naloxone nor did tolerance develop to the response. Injections directly into the hypothalamus suggested that, as with the fall in temperature after high doses of morphine, the hyperthermic effect is also due to an action on the preoptic/anterior hypothalamic thermoregulatory centers. Experiments measuring thermoregulatory behavior showed that rats delayed escaping from a heat load after low doses of morphine even though their core temperature was rising. These results suggest that low doses of morphine raise the set point of the central thermostats in rats resulting in a hyperthermia mediated, at least in part, by decreased cutaneous heat loss.", "contents": "Morphine hyperthermia in the rat: an action on the central thermostats. The mechanism underlying the hyperthermic response to low doses of morphine has been investigated in rats. Doses of morphine sulfate less than 10 mg/kg i.p. caused a rise in body temperature accompanied by vasoconstriction of the cutaneous blood vessels of the tail. This hyperthermia, unlike the hypothermia following higher doses of morphine was not blocked by naloxone nor did tolerance develop to the response. Injections directly into the hypothalamus suggested that, as with the fall in temperature after high doses of morphine, the hyperthermic effect is also due to an action on the preoptic/anterior hypothalamic thermoregulatory centers. Experiments measuring thermoregulatory behavior showed that rats delayed escaping from a heat load after low doses of morphine even though their core temperature was rising. These results suggest that low doses of morphine raise the set point of the central thermostats in rats resulting in a hyperthermia mediated, at least in part, by decreased cutaneous heat loss."} {"id": "PMID:1261602", "title": "Influence of group selective reagents in tissues containing alpha- and beta-adrenoceptors.", "content": "N-ethylmaleimide which is known to react irreversibly with free -SH groups of protein when incubated with rabbit aorta (alpha-adrenoreceptor) or atria (beta-adrenoreceptor) markedly depressed the dose-response curves of norepinephrine isomers in the aorta but not in atria. Dithiothreitol, a reagent which reduces S-S linkages caused a parallel shift of the dose-response curves of both isomers to an equal degree in aorta. However, in atria the reagent drastically and selectively reduced the maximal effects of (+)-norepinephrine and dopamine. This selective alteration of the (+)-isomer by the reagent probably reflects the conformational changes at the beta-adrenoreceptor. The concentrations of N-ethylmaleimide and dithiothreitol required to alter the activity of norepinephrine isomers was higher for atria than for aorta. It may be that alpha-adrenoreceptors are more susceptible than the beta-adrenoreceptors on the -SH group selective reagents. In the highest concentration tested, two other reagents 2,4-dimethoxybenzylamine and N-acetylimidazole, did not influence the activity of the steroisomers on aorta. In the presence of dithiothreitol, the pharmacologic effects of a nonadrenoreceptor stimulant drug, histamine was potentiated on aorta (H1) and not on atria (H2). Results are discussed in the light of similarity and dissimilarity of adrenoreceptors as reflected by the group selective reagents and the stereoisomers.", "contents": "Influence of group selective reagents in tissues containing alpha- and beta-adrenoceptors. N-ethylmaleimide which is known to react irreversibly with free -SH groups of protein when incubated with rabbit aorta (alpha-adrenoreceptor) or atria (beta-adrenoreceptor) markedly depressed the dose-response curves of norepinephrine isomers in the aorta but not in atria. Dithiothreitol, a reagent which reduces S-S linkages caused a parallel shift of the dose-response curves of both isomers to an equal degree in aorta. However, in atria the reagent drastically and selectively reduced the maximal effects of (+)-norepinephrine and dopamine. This selective alteration of the (+)-isomer by the reagent probably reflects the conformational changes at the beta-adrenoreceptor. The concentrations of N-ethylmaleimide and dithiothreitol required to alter the activity of norepinephrine isomers was higher for atria than for aorta. It may be that alpha-adrenoreceptors are more susceptible than the beta-adrenoreceptors on the -SH group selective reagents. In the highest concentration tested, two other reagents 2,4-dimethoxybenzylamine and N-acetylimidazole, did not influence the activity of the steroisomers on aorta. In the presence of dithiothreitol, the pharmacologic effects of a nonadrenoreceptor stimulant drug, histamine was potentiated on aorta (H1) and not on atria (H2). Results are discussed in the light of similarity and dissimilarity of adrenoreceptors as reflected by the group selective reagents and the stereoisomers."} {"id": "PMID:1261603", "title": "The role of alpha- and beta-adrenergic effects in the action of adrenaline on renal lithium elimination in adrenalectomized rats.", "content": "Repeated s.c. injections of L-adrenaline (4 X 0.5 mg/kg body weight) increased the urinary clearance of lithium in intact rats and in adrenalectomized animals. Adrenaline also increased the fractional excretion of lithium in adrenalectomized rats; an effect that was prevented by repeated s.c. injections of the alpha-adrenergic blocking agent phentolamine (4 X 1 mg/kg body weight). When administered alone, propranolol and phentolamine decreased the urinary clearance of lithium in adrenalectomized rats. The drug-induced changes in the urinary clearance of lithium were not directly related to the effects of the drugs on the urinary elimination of sodium, potassium, creatine and water. The results suggest that the action of adrenaline on renal lithium elimination in adrenalectomized rats might be mediated by alpha-adrenergic receptors.", "contents": "The role of alpha- and beta-adrenergic effects in the action of adrenaline on renal lithium elimination in adrenalectomized rats. Repeated s.c. injections of L-adrenaline (4 X 0.5 mg/kg body weight) increased the urinary clearance of lithium in intact rats and in adrenalectomized animals. Adrenaline also increased the fractional excretion of lithium in adrenalectomized rats; an effect that was prevented by repeated s.c. injections of the alpha-adrenergic blocking agent phentolamine (4 X 1 mg/kg body weight). When administered alone, propranolol and phentolamine decreased the urinary clearance of lithium in adrenalectomized rats. The drug-induced changes in the urinary clearance of lithium were not directly related to the effects of the drugs on the urinary elimination of sodium, potassium, creatine and water. The results suggest that the action of adrenaline on renal lithium elimination in adrenalectomized rats might be mediated by alpha-adrenergic receptors."} {"id": "PMID:1261604", "title": "Influence of sympathetic nerves on development of responsiveness of the chick smooth muscle to drugs.", "content": "The role of sympathetic nerves in the development of responsiveness of smooth muscle to drugs was investigated using the expansor secondariorum muscle of 2- to 40-day-old chicks. The normal developmental decrease in the responsiveness of the muscle to acetylcholine was prevented by surgical transection of the nerve or chronic treatment with guanethidine, while it was facilitated by chronic treatment with dimethylphenylpiperazinium. Sensitivity of the muscle to noradrenaline, remaining constant during normal development, was increased by nerve section or guanethidine treatment, while it was slightly decreased by dimethylphenylpipe-azinium treatment. These results suggest that sympathetic nerves regulate the development of the responsiveness of the chick expansor secundariorum muscle to drugs, at least the developmental decrease in responsiveness to acetylcholine.", "contents": "Influence of sympathetic nerves on development of responsiveness of the chick smooth muscle to drugs. The role of sympathetic nerves in the development of responsiveness of smooth muscle to drugs was investigated using the expansor secondariorum muscle of 2- to 40-day-old chicks. The normal developmental decrease in the responsiveness of the muscle to acetylcholine was prevented by surgical transection of the nerve or chronic treatment with guanethidine, while it was facilitated by chronic treatment with dimethylphenylpiperazinium. Sensitivity of the muscle to noradrenaline, remaining constant during normal development, was increased by nerve section or guanethidine treatment, while it was slightly decreased by dimethylphenylpipe-azinium treatment. These results suggest that sympathetic nerves regulate the development of the responsiveness of the chick expansor secundariorum muscle to drugs, at least the developmental decrease in responsiveness to acetylcholine."} {"id": "PMID:1261605", "title": "Changes in the fast component of the rabbit vena cava contraction after repeated stimulation by noradrenaline(NA).", "content": "The fast component of the rabbit vena cava contraction after repeated stimulation by NA was investigated. Experimental conditions which are known to increase the cellular calcium content led to an increase in contraction amplitude. Transient incubation between stimulations in a solution with high [Ca2+], in a solution with high [K], in a K+-free solution or in a solution containing ouabain is an example of such conditions. When the duration of a singly stimulus in a train of NA stimuli was prolonged the following contraction decreased. With increasing incubation time in Ca2+-free solution the maximum of contraction amplitude decreased far more after repeated stimulation than after a single stimulus. The results allow the interpretation that the fast component of the rabbit vena cava contraction which is induced by NA is related to the cellular calcium content. Moreover the results suggest that only a fraction of the cellular calcium is releasable by NA and that Ca2+-free conditions and/or NA exposure deplete this fraction.", "contents": "Changes in the fast component of the rabbit vena cava contraction after repeated stimulation by noradrenaline(NA). The fast component of the rabbit vena cava contraction after repeated stimulation by NA was investigated. Experimental conditions which are known to increase the cellular calcium content led to an increase in contraction amplitude. Transient incubation between stimulations in a solution with high [Ca2+], in a solution with high [K], in a K+-free solution or in a solution containing ouabain is an example of such conditions. When the duration of a singly stimulus in a train of NA stimuli was prolonged the following contraction decreased. With increasing incubation time in Ca2+-free solution the maximum of contraction amplitude decreased far more after repeated stimulation than after a single stimulus. The results allow the interpretation that the fast component of the rabbit vena cava contraction which is induced by NA is related to the cellular calcium content. Moreover the results suggest that only a fraction of the cellular calcium is releasable by NA and that Ca2+-free conditions and/or NA exposure deplete this fraction."} {"id": "PMID:1261606", "title": "Differential effect of baroreceptor reflexes and clonidine on frequency components of sympathetic discharge.", "content": "The effects of the baroreceptor reflexes and clonidine on the 3 and 10 Hz components of spontaneously occurring renal sympathetic nervous discharge (SND) were studied in the cat. The proportion of 3 : 10 Hz SND was assessed by selective filtering and integration of activity in the 2-4 Hz and 9-11 Hz frequency bands. Baroreceptor denervation increased activity in both frequency bands while significantly lowering the 3 : 10 Hz ratio. Baroreceptor reflex activation (i.v. phenylephrine) decreased activity in both frequency bands while significantly increasing the 3 : 10 ratio. Clonidine (4-20 mug/kg, i.v.) affected the 3 : 10 Hz ratio of SND in a manner similar to baroreceptor reflex activation. These results indicate that the 3 and 10 Hz components of SND, both of which have been previously shown to be inherent to the central vasomotor system, are differentially affected by the baroreceptor reflexes and clonidine. It is concluded that it is possible to characterize certain cardiovascular states with respect to the 3 : 10 Hz ratio of SND.", "contents": "Differential effect of baroreceptor reflexes and clonidine on frequency components of sympathetic discharge. The effects of the baroreceptor reflexes and clonidine on the 3 and 10 Hz components of spontaneously occurring renal sympathetic nervous discharge (SND) were studied in the cat. The proportion of 3 : 10 Hz SND was assessed by selective filtering and integration of activity in the 2-4 Hz and 9-11 Hz frequency bands. Baroreceptor denervation increased activity in both frequency bands while significantly lowering the 3 : 10 Hz ratio. Baroreceptor reflex activation (i.v. phenylephrine) decreased activity in both frequency bands while significantly increasing the 3 : 10 ratio. Clonidine (4-20 mug/kg, i.v.) affected the 3 : 10 Hz ratio of SND in a manner similar to baroreceptor reflex activation. These results indicate that the 3 and 10 Hz components of SND, both of which have been previously shown to be inherent to the central vasomotor system, are differentially affected by the baroreceptor reflexes and clonidine. It is concluded that it is possible to characterize certain cardiovascular states with respect to the 3 : 10 Hz ratio of SND."} {"id": "PMID:1261607", "title": "Differences in the mode of exucative reaction between early phase and late phase of carrageenin-induced inflammation in rats.", "content": "Differences in the mode of vascular permeability change induced by some stimulants such as chemical mediators between the early phase and the late phase of the carrageenin-induced granulomatous inflammation were investigated with the aid of 131I-human serum albumin as an indicator for the measurement of vascular permeability. In the early pregranulomatous phase of the inflammation, histamine injection into the inflammation locus markedly elevated local vascular permeability, while prostaglandins E1 and E2 showed no effect. On the other hand, in the late phase of the inflammation, where permanent granuloma tissue had been formed, prostaglandins E1 and E2 significantly enhanced the local vascular permeability, while histamine was inert.", "contents": "Differences in the mode of exucative reaction between early phase and late phase of carrageenin-induced inflammation in rats. Differences in the mode of vascular permeability change induced by some stimulants such as chemical mediators between the early phase and the late phase of the carrageenin-induced granulomatous inflammation were investigated with the aid of 131I-human serum albumin as an indicator for the measurement of vascular permeability. In the early pregranulomatous phase of the inflammation, histamine injection into the inflammation locus markedly elevated local vascular permeability, while prostaglandins E1 and E2 showed no effect. On the other hand, in the late phase of the inflammation, where permanent granuloma tissue had been formed, prostaglandins E1 and E2 significantly enhanced the local vascular permeability, while histamine was inert."} {"id": "PMID:1261608", "title": "Combinations of selected CNS depressants with d-amphetamine or mazindol on food intake and motor activity of rats.", "content": "Amobarbital, diazepam, prochlorperazine and thioridazine were tested alone and in combination with d-amphetamine or mazindol on food consumption and spontaneous motor activity in rats. Of the four depressants tested (1) only amobarbital enhanced the anorexic effects of d-amphetamine and (2) amobarbital, diazepam and prochlorperazine enhanced the hypermotility induced by d-amphetamine. None of the depressants altered the anorexic effect of mazindol but amobarbital and diazepam decreased and prochlorperazine increased the hypermotility induced by mazindol. These differential effects of the CNS depressants suggest that d-amphetamine and mazindol might have different mechanisms of anorexiant or stimulatory action. The data also suggest that, to achieve anorexia with diminished CNS stimulation, combinations of d-amphetamine and any of the tested CNS depressants seem to be precluded. In fact, this desired clinical objective might be achieved with combinations of mazindol and either amobarbital or diazepam.", "contents": "Combinations of selected CNS depressants with d-amphetamine or mazindol on food intake and motor activity of rats. Amobarbital, diazepam, prochlorperazine and thioridazine were tested alone and in combination with d-amphetamine or mazindol on food consumption and spontaneous motor activity in rats. Of the four depressants tested (1) only amobarbital enhanced the anorexic effects of d-amphetamine and (2) amobarbital, diazepam and prochlorperazine enhanced the hypermotility induced by d-amphetamine. None of the depressants altered the anorexic effect of mazindol but amobarbital and diazepam decreased and prochlorperazine increased the hypermotility induced by mazindol. These differential effects of the CNS depressants suggest that d-amphetamine and mazindol might have different mechanisms of anorexiant or stimulatory action. The data also suggest that, to achieve anorexia with diminished CNS stimulation, combinations of d-amphetamine and any of the tested CNS depressants seem to be precluded. In fact, this desired clinical objective might be achieved with combinations of mazindol and either amobarbital or diazepam."} {"id": "PMID:1261609", "title": "Clonidine-induced increase of renal prostaglandin activity and water diuresis in conscious dogs.", "content": "I.v. administration of clonidine to conscious dogs induces a water diuresis with hyposmotic urine and minor effect on electrolyte excretion. The diuresis is preceded by an increased urinary PGE excretion, but no change of urinary ADH output is observed. Plasma renin activity decreases. Both ADH infusion and indomethacin pretreatment inhibit the diuretic effect of clonidine. The results support the hypothesis that clonidine-induced water diuresis is mediated via an anti ADH effect due to increased renal prostaglandin activity. Moreover the results suggest that there is no direct stimulation of renin release by PGE.", "contents": "Clonidine-induced increase of renal prostaglandin activity and water diuresis in conscious dogs. I.v. administration of clonidine to conscious dogs induces a water diuresis with hyposmotic urine and minor effect on electrolyte excretion. The diuresis is preceded by an increased urinary PGE excretion, but no change of urinary ADH output is observed. Plasma renin activity decreases. Both ADH infusion and indomethacin pretreatment inhibit the diuretic effect of clonidine. The results support the hypothesis that clonidine-induced water diuresis is mediated via an anti ADH effect due to increased renal prostaglandin activity. Moreover the results suggest that there is no direct stimulation of renin release by PGE."} {"id": "PMID:1261620", "title": "Production of and response to erythropoietin in the splenectomized mouse.", "content": "A reliable dose-response curve has been established by exposing normal mice to graded doses of exogenous erythropoietin (ESF). In CF1 femal mice, made polycythemic by exposure to reduced air pressure , 59 Fe incorporation in RBC following injections of ESF (ranging from 0.05 to 3.2 IRP-units) varied according to the log of the ESF dose from 2.5 to 29.0 percent. Experiments with plethorized splenectomized mice showed unequivocally that they were able to respond to ESF, although their responses were very much smaller than that of intact mice, ranging from 1.4 to 12.0 percent. ESF activity was not detected in plasma from intact mice, but was evident in the plasma of mice that had been splenectomized 4 or 10 days earlier. Under conditions of hypoxia the plasma ESF level rose rapidly during the first 48 hours and then fell . In the plasma of splenectomized, similarly treated mice, the ESF level at every interval studied was much higher and was maintained for a longer time. Re-exposure to low oxygen tension for brief periods (2-24 h) produced and erythropoietic response in both intact and splenectomized polycythemic mice, its magnitude increasing with increased exposure time. The response of splenectomized mice, however, was lower than that of intact mice in spite of the fact that the plasma ESF level in the former was higher than in the latter.", "contents": "Production of and response to erythropoietin in the splenectomized mouse. A reliable dose-response curve has been established by exposing normal mice to graded doses of exogenous erythropoietin (ESF). In CF1 femal mice, made polycythemic by exposure to reduced air pressure , 59 Fe incorporation in RBC following injections of ESF (ranging from 0.05 to 3.2 IRP-units) varied according to the log of the ESF dose from 2.5 to 29.0 percent. Experiments with plethorized splenectomized mice showed unequivocally that they were able to respond to ESF, although their responses were very much smaller than that of intact mice, ranging from 1.4 to 12.0 percent. ESF activity was not detected in plasma from intact mice, but was evident in the plasma of mice that had been splenectomized 4 or 10 days earlier. Under conditions of hypoxia the plasma ESF level rose rapidly during the first 48 hours and then fell . In the plasma of splenectomized, similarly treated mice, the ESF level at every interval studied was much higher and was maintained for a longer time. Re-exposure to low oxygen tension for brief periods (2-24 h) produced and erythropoietic response in both intact and splenectomized polycythemic mice, its magnitude increasing with increased exposure time. The response of splenectomized mice, however, was lower than that of intact mice in spite of the fact that the plasma ESF level in the former was higher than in the latter."} {"id": "PMID:1261621", "title": "Adaptation and dynamics in X-cells and Y-cells of the cat retina.", "content": "On the basis of the spatial summation properties of their receptive fields, cat retinal ganglion cells were classified as either X-cells (linear) or Y-cells (non-linear). Responses were then obtained to a small, centered spot, square-wave modulated in time and superimposed on various levels of diffuse, steady background illumination. When fully dark-adapted, both X-cells and Y-cells produced responses that were entirely sustained. When well light-adapted but still in the scotopic range, both cell types produced largely transient responses with only a very small sustained component. The sustained or transient nature of responses is, therefore, not an invariant characteristic of X-cells and Y-cells in the scotopic range. We also conclude that the mechanism which controls the center's sensitivity in the scotopic range is similar though not identical in the two types of cells.", "contents": "Adaptation and dynamics in X-cells and Y-cells of the cat retina. On the basis of the spatial summation properties of their receptive fields, cat retinal ganglion cells were classified as either X-cells (linear) or Y-cells (non-linear). Responses were then obtained to a small, centered spot, square-wave modulated in time and superimposed on various levels of diffuse, steady background illumination. When fully dark-adapted, both X-cells and Y-cells produced responses that were entirely sustained. When well light-adapted but still in the scotopic range, both cell types produced largely transient responses with only a very small sustained component. The sustained or transient nature of responses is, therefore, not an invariant characteristic of X-cells and Y-cells in the scotopic range. We also conclude that the mechanism which controls the center's sensitivity in the scotopic range is similar though not identical in the two types of cells."} {"id": "PMID:1261622", "title": "Behavioral correlates of focal hippocampal x-irradiation in rats.", "content": "A study presenting findings of focal hippocampal x-irradiation in early infancy and late behavior at two ages was carried out using Long-Evans hooded rats (Rattus norvegicus). Animals from eleven litters received 150-R irradiation treatments for 5 or 15 consecutive days and were then tested in an open field situation and in a two-way active avoidance apparatus. The results indicated that the behavioral deficits paralleled those seen in animals with classical hippocampal lesions. The results were offered in support of a response suppression model for hippocampal functioning.", "contents": "Behavioral correlates of focal hippocampal x-irradiation in rats. A study presenting findings of focal hippocampal x-irradiation in early infancy and late behavior at two ages was carried out using Long-Evans hooded rats (Rattus norvegicus). Animals from eleven litters received 150-R irradiation treatments for 5 or 15 consecutive days and were then tested in an open field situation and in a two-way active avoidance apparatus. The results indicated that the behavioral deficits paralleled those seen in animals with classical hippocampal lesions. The results were offered in support of a response suppression model for hippocampal functioning."} {"id": "PMID:1261623", "title": "Excitatory nature of dopamine in the nigro-caudate pathway.", "content": "Inputs from the substantia nigra (SN) to the caudate nucleus (Cd) and the effects of electrophoretic dopamine on Cd neurones were studied in cats anaesthetized with pentobarbitone with intracellular techniques. Single shock electrical stimulation of the SN or the medial forebrain bundle (MFB) induced monosynaptic EPSPs in Cd neurones. Dopamine depolarized Cd neurones and chlorpromazine suppressed the SN or MFB induced EPSPs. Appropriate controls indicate that the drug effects were not artifactual. Some recorded neurones were identified by procion yellow dye injection as the medium-size intrinsic Cd neurones.", "contents": "Excitatory nature of dopamine in the nigro-caudate pathway. Inputs from the substantia nigra (SN) to the caudate nucleus (Cd) and the effects of electrophoretic dopamine on Cd neurones were studied in cats anaesthetized with pentobarbitone with intracellular techniques. Single shock electrical stimulation of the SN or the medial forebrain bundle (MFB) induced monosynaptic EPSPs in Cd neurones. Dopamine depolarized Cd neurones and chlorpromazine suppressed the SN or MFB induced EPSPs. Appropriate controls indicate that the drug effects were not artifactual. Some recorded neurones were identified by procion yellow dye injection as the medium-size intrinsic Cd neurones."} {"id": "PMID:1261624", "title": "A comparison of primary afferent and cortical neurone activity coding sinus hair movements in the cat.", "content": "Responses in the somatosensory cortical area S I to stimulation of facial sinus hairs were recorded in the anaesthetized cat and compared with activity in primary afferent fibres innervating vibrissae follicles. The specific cortical vibrissa area is somatotopically organized; 39% of the cortical units in that area responded to stimulation of only a single sinus hair but in some cases all maxillary vibrissae activated a single cortical neurone. The responses consisted of three major groups; either a phasic discharge in response to the movement part of a stimulus, or an additional tonic discharge related to the steady period of vibrissa deflection, or a tonic discharge. On the basis of a comparison of response and excitability characteristics of primary afferent and cortical neurones it is concluded that all four kinds of peripheral units innervating sinus hair follicles project to the somatosensory cortical area S I. It appears from these findings that some cortical neurones receive a specific input related to a particular component of the complex primary afferent response in fibres innervating sinus hair follicles. The results are discussed with respect to previous reports on the central representation of facial sinus hairs in different species.", "contents": "A comparison of primary afferent and cortical neurone activity coding sinus hair movements in the cat. Responses in the somatosensory cortical area S I to stimulation of facial sinus hairs were recorded in the anaesthetized cat and compared with activity in primary afferent fibres innervating vibrissae follicles. The specific cortical vibrissa area is somatotopically organized; 39% of the cortical units in that area responded to stimulation of only a single sinus hair but in some cases all maxillary vibrissae activated a single cortical neurone. The responses consisted of three major groups; either a phasic discharge in response to the movement part of a stimulus, or an additional tonic discharge related to the steady period of vibrissa deflection, or a tonic discharge. On the basis of a comparison of response and excitability characteristics of primary afferent and cortical neurones it is concluded that all four kinds of peripheral units innervating sinus hair follicles project to the somatosensory cortical area S I. It appears from these findings that some cortical neurones receive a specific input related to a particular component of the complex primary afferent response in fibres innervating sinus hair follicles. The results are discussed with respect to previous reports on the central representation of facial sinus hairs in different species."} {"id": "PMID:1261625", "title": "Projections from the lateral reticular nucleus to the cerebellar cortex and nuclei in the cat.", "content": "The fiber projection from the lateral reticular nucleus (LRN) to the cerebellum was examined in the cat. Electrolytic lesions were placed in a confined area of the LRN using a parapharyngeal approach, and the ensuing degeneration was studied in sections stained by the Nauta and the Fink-Heimer methods. Fibers from the LRN ascend the ipsilateral restiform body, terminating bilaterally but chiefly in the ipsilateral cerebellum. In the ipsilateral cortex projections were found to lobules I to V, with denser terminations in sublobules IVb to Ve. The projections are stronger in the intermediate-lateral zones than in the vermis proper. There is also a dense projection to sublobules VId and VIf and to the medialmost part of the simple lobule (HVI). Scanty termination was seen in the medialmost part of crus I. There is a moderate projection to the caudalmost folium of sublobule VIIb and to the rostral folia of sublobule VIIIa and the paramedian lobule. The contralateral projection by fibers crossed within the cerebellum is far less dense but clearcut in the anterior lobe, the rostral folia of lobule VI and the medial part of the simple lobule. In the ipsilateral nuclei strong projections were found to rostral portions of the medial nucleus (M) and the caudal two thirds of the anterior interpositus nucleus (IA) with predominance in the lateral part of the latter. A focal projection was found to rostrodorsal portions of the posterior interpositus nucleus (IP). No projection was found to the lateral nucleus (L). Contralaterally there is a weak projection to the rostral part of M and the medial parts of IA and IP.", "contents": "Projections from the lateral reticular nucleus to the cerebellar cortex and nuclei in the cat. The fiber projection from the lateral reticular nucleus (LRN) to the cerebellum was examined in the cat. Electrolytic lesions were placed in a confined area of the LRN using a parapharyngeal approach, and the ensuing degeneration was studied in sections stained by the Nauta and the Fink-Heimer methods. Fibers from the LRN ascend the ipsilateral restiform body, terminating bilaterally but chiefly in the ipsilateral cerebellum. In the ipsilateral cortex projections were found to lobules I to V, with denser terminations in sublobules IVb to Ve. The projections are stronger in the intermediate-lateral zones than in the vermis proper. There is also a dense projection to sublobules VId and VIf and to the medialmost part of the simple lobule (HVI). Scanty termination was seen in the medialmost part of crus I. There is a moderate projection to the caudalmost folium of sublobule VIIb and to the rostral folia of sublobule VIIIa and the paramedian lobule. The contralateral projection by fibers crossed within the cerebellum is far less dense but clearcut in the anterior lobe, the rostral folia of lobule VI and the medial part of the simple lobule. In the ipsilateral nuclei strong projections were found to rostral portions of the medial nucleus (M) and the caudal two thirds of the anterior interpositus nucleus (IA) with predominance in the lateral part of the latter. A focal projection was found to rostrodorsal portions of the posterior interpositus nucleus (IP). No projection was found to the lateral nucleus (L). Contralaterally there is a weak projection to the rostral part of M and the medial parts of IA and IP."} {"id": "PMID:1261661", "title": "[Determination of absolute configuration of amine compounds of pharmaceutical interest by means of measurement of circular dichroism].", "content": "The CD curves study of the pyridyl-N-oxide derivatives of some adrenergic and anorexigenic amines showed that the sign of the Cotton effect can be related to their absolute configuration. The obtained results confirm the absolute configuration of fenfluramine and nor-fenfluramine and suggest that the levo isomer of ortoxine has R-configuration.", "contents": "[Determination of absolute configuration of amine compounds of pharmaceutical interest by means of measurement of circular dichroism]. The CD curves study of the pyridyl-N-oxide derivatives of some adrenergic and anorexigenic amines showed that the sign of the Cotton effect can be related to their absolute configuration. The obtained results confirm the absolute configuration of fenfluramine and nor-fenfluramine and suggest that the levo isomer of ortoxine has R-configuration."} {"id": "PMID:1261662", "title": "[Drug-protein interactions: physico-chemical study on the interactions between chlorpromazine and glutamate dehydrogenase].", "content": "The molecular basis of inhibition of glutamate dehydrogenase by chlorpromazine was studied by circular dichoroism, differential spectroscopy and fluorescence. Chlorpromazine appears to induce conformational changes of the enzyme at the position of aromatic amino acids, and tryptophan residues in particular are involved. On the other hand the secondary structure of the enzyme is not influenced by binding of the drug.", "contents": "[Drug-protein interactions: physico-chemical study on the interactions between chlorpromazine and glutamate dehydrogenase]. The molecular basis of inhibition of glutamate dehydrogenase by chlorpromazine was studied by circular dichoroism, differential spectroscopy and fluorescence. Chlorpromazine appears to induce conformational changes of the enzyme at the position of aromatic amino acids, and tryptophan residues in particular are involved. On the other hand the secondary structure of the enzyme is not influenced by binding of the drug."} {"id": "PMID:1261663", "title": "[Condensation of N-alkyl-o-phenylendiamine with ethyl benzoylacetate].", "content": "By reaction in hot xylene of ethyl benzoylacetate with N-methyl-o-phenylenediamine (I a) and N-benzyl-o-phenylenediamine (I b) three five-membered ring compounds and one seven-membered ring compound were obtained. Compounds isolated were: 1-alkyl-2-phenacylbenzimidazoles (III), 1-alkyl-2-phenylbenzimidazoles (V), 1-alkyl-2-methylbenzimidazoles (VI) and 1-alkyl-4-phenyl-1,3-dihydro-2H-1,5-benzodiazepine-2-ones (IV). In the reaction with N-benzyl-o-phenylenediamine we isolated also the N-benzyl-2-benzoylacetamidoaniline (II b), which by further heating in xylene gave (IV b). The structures of compounds were elucidated from their chemical reactivity and their N.M.R. and I.R. spectra.", "contents": "[Condensation of N-alkyl-o-phenylendiamine with ethyl benzoylacetate]. By reaction in hot xylene of ethyl benzoylacetate with N-methyl-o-phenylenediamine (I a) and N-benzyl-o-phenylenediamine (I b) three five-membered ring compounds and one seven-membered ring compound were obtained. Compounds isolated were: 1-alkyl-2-phenacylbenzimidazoles (III), 1-alkyl-2-phenylbenzimidazoles (V), 1-alkyl-2-methylbenzimidazoles (VI) and 1-alkyl-4-phenyl-1,3-dihydro-2H-1,5-benzodiazepine-2-ones (IV). In the reaction with N-benzyl-o-phenylenediamine we isolated also the N-benzyl-2-benzoylacetamidoaniline (II b), which by further heating in xylene gave (IV b). The structures of compounds were elucidated from their chemical reactivity and their N.M.R. and I.R. spectra."} {"id": "PMID:1261664", "title": "[Potential anti-inflammatory agents II. 7-Methyl-s-triazo(4,3-a)pyridines].", "content": "A synthesis of eight derivatives of 7-methyl-s-triazo-[4,3-a]pyridine substituted in position 3, has been made with a view to studying their possible antiinflammatory and analgesic action. Among the obtained compounds only the 3-(alpha-hydroxyethyl)-7-methyl-s-triazo[4,3-a]pyridine presents an activity similar to aspirin.", "contents": "[Potential anti-inflammatory agents II. 7-Methyl-s-triazo(4,3-a)pyridines]. A synthesis of eight derivatives of 7-methyl-s-triazo-[4,3-a]pyridine substituted in position 3, has been made with a view to studying their possible antiinflammatory and analgesic action. Among the obtained compounds only the 3-(alpha-hydroxyethyl)-7-methyl-s-triazo[4,3-a]pyridine presents an activity similar to aspirin."} {"id": "PMID:1261665", "title": "[Phthalimide derivatives of pyrimidine and thiazole heterocyclics].", "content": "The synthesis of some phthalimido-derivatives of the pyrimidine and thiazole ring systems is described. The functional groups have been suitably selected to enhance structural analogy with the pairs of pyrimidine and purine bases present in nucleic acids. In preliminary tests some of these compounds have shown inhibitory activity towards RNA polymerase reaction in vitro.", "contents": "[Phthalimide derivatives of pyrimidine and thiazole heterocyclics]. The synthesis of some phthalimido-derivatives of the pyrimidine and thiazole ring systems is described. The functional groups have been suitably selected to enhance structural analogy with the pairs of pyrimidine and purine bases present in nucleic acids. In preliminary tests some of these compounds have shown inhibitory activity towards RNA polymerase reaction in vitro."} {"id": "PMID:1261666", "title": "Receptor sites of DNA for the photoreaction with psoralen.", "content": "Biological and pharmacological effects of psoralens are correlated to their capacity to photoreact with pyrimidine bases of native DNA and in particular to form inter-strand cross-linkages. To determine possible prefenrential sites for the photoreaction the Authors have studied the capacity of psoralen to form complexes and to photoreact with various polynucleotides. The Authors have shown that specific sites exist in DNA for the photochemical interaction with psoralen; these sequences which can be considered as specific receptors for photobiological activity of psoralen are represented by alternate sequences in every strand of A and T, corresponding to poly d(A--T) - poly d(A--T). These receptor sites show a high capacity for intercalation and successive photoreaction with psoralen.", "contents": "Receptor sites of DNA for the photoreaction with psoralen. Biological and pharmacological effects of psoralens are correlated to their capacity to photoreact with pyrimidine bases of native DNA and in particular to form inter-strand cross-linkages. To determine possible prefenrential sites for the photoreaction the Authors have studied the capacity of psoralen to form complexes and to photoreact with various polynucleotides. The Authors have shown that specific sites exist in DNA for the photochemical interaction with psoralen; these sequences which can be considered as specific receptors for photobiological activity of psoralen are represented by alternate sequences in every strand of A and T, corresponding to poly d(A--T) - poly d(A--T). These receptor sites show a high capacity for intercalation and successive photoreaction with psoralen."} {"id": "PMID:1261667", "title": "Synthesis and neuropharmacology of cyclobutanecarboxylic acid derivatives.", "content": "Urea, hydrazide and amide derivatives of cyclobutanecarboxylic acid have been examined for central nervous systems depressant properties, potentiation of barbiturate induced sleep, myorelaxant, antitremorine and anticonvulsant activity. The urea derivatives have central nervous system depressant qualities while the hydrazines and heterocyclic amides are either inactive or have central nervous system excitatory properties. N,N'-o-methoxybenzylidenebiscyclobutanecarboxamide and 1,3-dicyclo-butanecarbonyl-2-thiourea are myorelaxant; 1-cyclobutanecarbonyl-3-allylurea antagonizes Metrazol induced convulsions; 1,3-dicyclobutanecarbonyl-2-thiourea and N-cyclobutanecarbonyl morpholine antagonizes tremorine induced tremors.", "contents": "Synthesis and neuropharmacology of cyclobutanecarboxylic acid derivatives. Urea, hydrazide and amide derivatives of cyclobutanecarboxylic acid have been examined for central nervous systems depressant properties, potentiation of barbiturate induced sleep, myorelaxant, antitremorine and anticonvulsant activity. The urea derivatives have central nervous system depressant qualities while the hydrazines and heterocyclic amides are either inactive or have central nervous system excitatory properties. N,N'-o-methoxybenzylidenebiscyclobutanecarboxamide and 1,3-dicyclo-butanecarbonyl-2-thiourea are myorelaxant; 1-cyclobutanecarbonyl-3-allylurea antagonizes Metrazol induced convulsions; 1,3-dicyclobutanecarbonyl-2-thiourea and N-cyclobutanecarbonyl morpholine antagonizes tremorine induced tremors."} {"id": "PMID:1261668", "title": "Synthesis and pharmacological properties of derivatives of pyrrolo(3,4-d)pyrimidines and pyrrolo(3,4-b)pyridines (I).", "content": "The synthesis of variously substituted pyrrolo[3,4-d]pyrimidines and pyrrolo[3,4-b]pyridines is reported. Some of the compounds act as reducers of the carrageenin edema in the rat and as inhibitors of prostaglandin biosynthesis in a microsomal preparation of bovine seminal vesicles.", "contents": "Synthesis and pharmacological properties of derivatives of pyrrolo(3,4-d)pyrimidines and pyrrolo(3,4-b)pyridines (I). The synthesis of variously substituted pyrrolo[3,4-d]pyrimidines and pyrrolo[3,4-b]pyridines is reported. Some of the compounds act as reducers of the carrageenin edema in the rat and as inhibitors of prostaglandin biosynthesis in a microsomal preparation of bovine seminal vesicles."} {"id": "PMID:1261669", "title": "[Synthesis of substituted 1-benzyl-1,2,3,4-tetrahydroisoquinolines].", "content": "Several derivatives of 1-benzyl-1,2,3,4-tetrahydroisoquinoline have been synthesized in order to evaluate their potential cardiovascular activities. These compounds, which can be related to Trimethoquinol and tetrahydropapaverin, showed no interesting activities in preliminary pharmacological screening.", "contents": "[Synthesis of substituted 1-benzyl-1,2,3,4-tetrahydroisoquinolines]. Several derivatives of 1-benzyl-1,2,3,4-tetrahydroisoquinoline have been synthesized in order to evaluate their potential cardiovascular activities. These compounds, which can be related to Trimethoquinol and tetrahydropapaverin, showed no interesting activities in preliminary pharmacological screening."} {"id": "PMID:1261707", "title": "Environmental and genetic factors affecting the response of laboratory animals to drugs.", "content": "Only some of the diverse factors that can affect drug disposition and response in laboratory animals have been identified at the present time. These numerous factors contribute to large day-to-day variations that have become a major problem impeding investigation of drug disposition and response in laboratory animals. Although these variations render many experiments difficult to interpret and produce large discrepancies in the literature, few published investigations using laboratory animals provide sufficient details to permit replication of the studies under similar conditions with respect to these variables. Thus, the importance of these variables in affecting results is apparently insufficiently recognized at present. Two commonly overlooked variables affecting the activity of hepatic microsomal enzymes (HME) in rodents and hence the rate at which rodents eliminate from their bodies many foreign compounds are the bedding under the wire mesh cage and the relative cleanliness of the environment. Numerous chemicals present in relatively low concentrations in the environment of the animal room can significantly alter HME activity. Representative of these chemicals are aromatic hydrocarbons in cedarwood bedding, eucalyptol from aerosol sprays, and chlorinated hydrocarbon insecticides, each of which induces HME activity, whereas ammonia generated from feces and urine accumulated in unchanged pans under cages may inhibit HME activity. Chloroform, identified as an environmental contaminant of the water and air of certain cities, exhibits sex and strain differences with respect to toxicity (LD50) in mice. After intraperitoneal injection, twice as much chloroform accumulated in the kidneys of males from the sensitive strain (DBA/2J) as from the resistant (C57BL/6J) strain. First generation offspring were midway between parental strains both with respect to LD50 and renal accumulation of chloroform.", "contents": "Environmental and genetic factors affecting the response of laboratory animals to drugs. Only some of the diverse factors that can affect drug disposition and response in laboratory animals have been identified at the present time. These numerous factors contribute to large day-to-day variations that have become a major problem impeding investigation of drug disposition and response in laboratory animals. Although these variations render many experiments difficult to interpret and produce large discrepancies in the literature, few published investigations using laboratory animals provide sufficient details to permit replication of the studies under similar conditions with respect to these variables. Thus, the importance of these variables in affecting results is apparently insufficiently recognized at present. Two commonly overlooked variables affecting the activity of hepatic microsomal enzymes (HME) in rodents and hence the rate at which rodents eliminate from their bodies many foreign compounds are the bedding under the wire mesh cage and the relative cleanliness of the environment. Numerous chemicals present in relatively low concentrations in the environment of the animal room can significantly alter HME activity. Representative of these chemicals are aromatic hydrocarbons in cedarwood bedding, eucalyptol from aerosol sprays, and chlorinated hydrocarbon insecticides, each of which induces HME activity, whereas ammonia generated from feces and urine accumulated in unchanged pans under cages may inhibit HME activity. Chloroform, identified as an environmental contaminant of the water and air of certain cities, exhibits sex and strain differences with respect to toxicity (LD50) in mice. After intraperitoneal injection, twice as much chloroform accumulated in the kidneys of males from the sensitive strain (DBA/2J) as from the resistant (C57BL/6J) strain. First generation offspring were midway between parental strains both with respect to LD50 and renal accumulation of chloroform."} {"id": "PMID:1261708", "title": "Environmental factors in drug metabolism.", "content": "Although various kinds of environmental factors may alter the activity of cytochrome P-450 enzymes in liver micromes, their effects on the pharmacokinetics of drugs and other foreign compounds in living animals may not be as great as might be predicted from assays of these enzymes in vitro. Indeed, the effects will depend on the relative importance of excretory and metabolic mechanisms in the elimination of the drug, the relative importance of various metabolic reactions in different tissues, the extraction ratio of the drug by the liver, and in some instances on the route of administration of the drug. Moreover, the effect of the various environmental factors on the pharmacologic and the toxicologic actions of the drug will depend on whether these actions are caused by the parent foreign compounds or by one or more of their metabolites. It may also be important that the environmental factors may alter not only relative activiteis of the cytochrome P-450 in liver microsomes but also the activities of other drug-metabolizing enzymes and that the relative effects of the environmental factors of these enzymes may differ depending on the animal species or the animal strain. Indeed, a given factor may increase the pharmacologic effects of a drug metabolite in one animal species but decrease it in another. For these reasons, it frequently is not possible to predict the effects of environmental factors on drug action in living animals solely from in vitro rates of metabolism of model substrates.", "contents": "Environmental factors in drug metabolism. Although various kinds of environmental factors may alter the activity of cytochrome P-450 enzymes in liver micromes, their effects on the pharmacokinetics of drugs and other foreign compounds in living animals may not be as great as might be predicted from assays of these enzymes in vitro. Indeed, the effects will depend on the relative importance of excretory and metabolic mechanisms in the elimination of the drug, the relative importance of various metabolic reactions in different tissues, the extraction ratio of the drug by the liver, and in some instances on the route of administration of the drug. Moreover, the effect of the various environmental factors on the pharmacologic and the toxicologic actions of the drug will depend on whether these actions are caused by the parent foreign compounds or by one or more of their metabolites. It may also be important that the environmental factors may alter not only relative activiteis of the cytochrome P-450 in liver microsomes but also the activities of other drug-metabolizing enzymes and that the relative effects of the environmental factors of these enzymes may differ depending on the animal species or the animal strain. Indeed, a given factor may increase the pharmacologic effects of a drug metabolite in one animal species but decrease it in another. For these reasons, it frequently is not possible to predict the effects of environmental factors on drug action in living animals solely from in vitro rates of metabolism of model substrates."} {"id": "PMID:1261712", "title": "Inherited progressive epilepsy of the dog with comparisons to Lafora's disease of man.", "content": "A familial progressive form of epilepsy in the beagle dog is clinically characterized by intermittent seizures, often of grand mal type. If not properly treated, the seizures may lead to status epilepticus. The seizures are often elicited by external stimuli, especially a change in noise or light in the surroundings. Histologically, intracytoplasmic inclusions, 2-10 mum in diameter, occur in glial and neuronal cells in the brain, especially the thalamus. The inclusions are strongly positive for carbohydrate stains, weakly metachromatic, and lipid negative. They are spherical with a dense core and an often radiating, less dense periphery. Histologic changes in other organs include basophilic myocardial degeneration, degeneration and variation in diameter size of skeletal muscle fibers, and deposition of periodic acid-Schiff positive material in the cytoplasm of reticuloendothelial cells of the liver, spleen, and lymph nodes. Based on clinical and morphologic manifestations, the beagle disorder resembles Lafora's disease of man. This disorder will provide a useful model for comparative studies with progressive myoclonic epilepsy (Lafora's disease) of man and for defining the pathomechanisms of other forms of epilepsy.", "contents": "Inherited progressive epilepsy of the dog with comparisons to Lafora's disease of man. A familial progressive form of epilepsy in the beagle dog is clinically characterized by intermittent seizures, often of grand mal type. If not properly treated, the seizures may lead to status epilepticus. The seizures are often elicited by external stimuli, especially a change in noise or light in the surroundings. Histologically, intracytoplasmic inclusions, 2-10 mum in diameter, occur in glial and neuronal cells in the brain, especially the thalamus. The inclusions are strongly positive for carbohydrate stains, weakly metachromatic, and lipid negative. They are spherical with a dense core and an often radiating, less dense periphery. Histologic changes in other organs include basophilic myocardial degeneration, degeneration and variation in diameter size of skeletal muscle fibers, and deposition of periodic acid-Schiff positive material in the cytoplasm of reticuloendothelial cells of the liver, spleen, and lymph nodes. Based on clinical and morphologic manifestations, the beagle disorder resembles Lafora's disease of man. This disorder will provide a useful model for comparative studies with progressive myoclonic epilepsy (Lafora's disease) of man and for defining the pathomechanisms of other forms of epilepsy."} {"id": "PMID:1261713", "title": "Muscular dystrophy of mink: a new animal model.", "content": "Muscular dystrophies comprise an important group of inherited disorders of man. Although the disease has been studied extensively, little is known about the underlying primary pathomechanisms. Consequently, treatment of patients is difficult and prognosis is poor. An animal model of muscular dystrophy is a useful research tool for approaching the basic problems of pathogenesis in muscle diseases. An inherited progressive muscular dystrophy of mink which resembles the amyotonic forms of human muscular dystrophy is currently under study. Clinically, the earliest sign is progressive muscular weakness and atrophy. Muscle enzyme activities in serum are usually elevated to pathologic levels. Urinary creatine/creatinine ratio is elevated. Pathologic changes are limited to skeletal muscle and are typical of those seen in amyotonic forms of human muscular dystrophy. These changes include variation in diameter size of muscle fibers, centralized nuclei, floccular and hyaline degeneration of scattered muscle fibers, increase in connective tissue in endomysial and perimysial areas, and regenerative attempts. Both type I and type II muscle fibers are involved in the disease process. Genetic studies indicate an autosomal recessive mode of inheritance. Although the primary defect in muscular dystrophy is traditionally thought to reside in skeletal muscle, recent studies have produced theories of primary involvement of other tissues and organ systems. These theories are presented and relationships to the traditional theory are discussed.", "contents": "Muscular dystrophy of mink: a new animal model. Muscular dystrophies comprise an important group of inherited disorders of man. Although the disease has been studied extensively, little is known about the underlying primary pathomechanisms. Consequently, treatment of patients is difficult and prognosis is poor. An animal model of muscular dystrophy is a useful research tool for approaching the basic problems of pathogenesis in muscle diseases. An inherited progressive muscular dystrophy of mink which resembles the amyotonic forms of human muscular dystrophy is currently under study. Clinically, the earliest sign is progressive muscular weakness and atrophy. Muscle enzyme activities in serum are usually elevated to pathologic levels. Urinary creatine/creatinine ratio is elevated. Pathologic changes are limited to skeletal muscle and are typical of those seen in amyotonic forms of human muscular dystrophy. These changes include variation in diameter size of muscle fibers, centralized nuclei, floccular and hyaline degeneration of scattered muscle fibers, increase in connective tissue in endomysial and perimysial areas, and regenerative attempts. Both type I and type II muscle fibers are involved in the disease process. Genetic studies indicate an autosomal recessive mode of inheritance. Although the primary defect in muscular dystrophy is traditionally thought to reside in skeletal muscle, recent studies have produced theories of primary involvement of other tissues and organ systems. These theories are presented and relationships to the traditional theory are discussed."} {"id": "PMID:1261715", "title": "Dietary constituents altering the responses to chemical carcinogens.", "content": "This paper deals with two categories of compounds having the capacity to inhibit the neoplastic effects of chemical carcinogens on the host. The first are inducers of increased microsomal mixed function oxidase activity. An increasing number of these inducers are being found in natural products. Cruciferous vegetables including brussels sprouts, cabbage, and cauliflower contain such compounds. Recently indole-3-acetonitrile, indole-3-carbinol and 3,3'-diindolylmethane have been identified as inducers in these three plants. Other naturally occurring inducers include flavones, safrole, isosafrole, beta-ionone, and oxidized sterols. Since previous work has shown that synthetic inducers may protect against chemical carcinogens, the composition of the diet could play a role in inhibiting the neoplastic response to these carcinogenic agents. The second category of inhibitors comprises the antioxidants. Several of these compounds have been found to inhibit the carcinogenic effects of a variety of chemical carcinogens. Considerable work of this nature has been done with butylated hydroxyanisole and butylated hydroxytoluene two antioxidants extensively used as food additives. Other antioxidants having carcinogen inhibiting capacities include ethoxyquin, disulfiram, and dimethyldithiocarbamate.", "contents": "Dietary constituents altering the responses to chemical carcinogens. This paper deals with two categories of compounds having the capacity to inhibit the neoplastic effects of chemical carcinogens on the host. The first are inducers of increased microsomal mixed function oxidase activity. An increasing number of these inducers are being found in natural products. Cruciferous vegetables including brussels sprouts, cabbage, and cauliflower contain such compounds. Recently indole-3-acetonitrile, indole-3-carbinol and 3,3'-diindolylmethane have been identified as inducers in these three plants. Other naturally occurring inducers include flavones, safrole, isosafrole, beta-ionone, and oxidized sterols. Since previous work has shown that synthetic inducers may protect against chemical carcinogens, the composition of the diet could play a role in inhibiting the neoplastic response to these carcinogenic agents. The second category of inhibitors comprises the antioxidants. Several of these compounds have been found to inhibit the carcinogenic effects of a variety of chemical carcinogens. Considerable work of this nature has been done with butylated hydroxyanisole and butylated hydroxytoluene two antioxidants extensively used as food additives. Other antioxidants having carcinogen inhibiting capacities include ethoxyquin, disulfiram, and dimethyldithiocarbamate."} {"id": "PMID:1261731", "title": "Short-term measurement of D-xylose uptake by isolated rat soleus muscle.", "content": "The uptake of D-[U-14C]xylose by isolated rat soleus muscle was studied, using D-[1-3H]-sorbitol as an extracellular marker. Xylose uptake was limited by the diffusion of the sugar into and through the extracellular water. This could be overcome in part by allowing the test sugars to pre-equilibrate in the extracellular water at 0 degrees C, before measuring xylose uptake. It was not necessary to fill the extracellular water with the test sugars to obtain maximum rates of xylose uptake. From this it was concluded that the sugar carrier sites were located in a specific region on the plasma membrane, readily accessible to sugar carrier sites were located in a specific region on the plasma membrane, readily accessible to sugars entering the interstitial water. Pre-equilibration was more effective in the absence of insulin than in the presence of the hormone. This suggested that insulin may influence sugar uptake at some site prior to the cell membrane. Pre-incubation at 0 degrees C itself stimulated sugar transport. This effect of cooling was not influenced by insulin, nor did it appear to affect the stimulatory action of insulin on xylose transport.", "contents": "Short-term measurement of D-xylose uptake by isolated rat soleus muscle. The uptake of D-[U-14C]xylose by isolated rat soleus muscle was studied, using D-[1-3H]-sorbitol as an extracellular marker. Xylose uptake was limited by the diffusion of the sugar into and through the extracellular water. This could be overcome in part by allowing the test sugars to pre-equilibrate in the extracellular water at 0 degrees C, before measuring xylose uptake. It was not necessary to fill the extracellular water with the test sugars to obtain maximum rates of xylose uptake. From this it was concluded that the sugar carrier sites were located in a specific region on the plasma membrane, readily accessible to sugar carrier sites were located in a specific region on the plasma membrane, readily accessible to sugars entering the interstitial water. Pre-equilibration was more effective in the absence of insulin than in the presence of the hormone. This suggested that insulin may influence sugar uptake at some site prior to the cell membrane. Pre-incubation at 0 degrees C itself stimulated sugar transport. This effect of cooling was not influenced by insulin, nor did it appear to affect the stimulatory action of insulin on xylose transport."} {"id": "PMID:1261732", "title": "Immunohistochemical localization of somatostatin in endocrine cells of the rat stomach.", "content": "Using an immunohistochemical technique involving unlabeled antibody and the peroxidase-anti-peroxidase complex, we have localized somatostatin (or growth hormone-release inhibiting hormone), a hypothalamic hormone which can also inhibit gastrin secretion, in the rat stomach. Somatostatin was found to be present in a few cells in the mucosa of the pyloric antrum. These cells are characterized by the presence of secretory granules of about 150-250 nm in diameter and are probably endocrine cells.", "contents": "Immunohistochemical localization of somatostatin in endocrine cells of the rat stomach. Using an immunohistochemical technique involving unlabeled antibody and the peroxidase-anti-peroxidase complex, we have localized somatostatin (or growth hormone-release inhibiting hormone), a hypothalamic hormone which can also inhibit gastrin secretion, in the rat stomach. Somatostatin was found to be present in a few cells in the mucosa of the pyloric antrum. These cells are characterized by the presence of secretory granules of about 150-250 nm in diameter and are probably endocrine cells."} {"id": "PMID:1261733", "title": "[Serologic diagnosis of bovine and ovine brucellosis by a buffered antigen test].", "content": "In the first part the authors compare the results of the test effected by means of a buffered antigen (EAT) whose cellular concentration was about 10%, with those of slow seroagglutination (SAW) and complement fixation (FC). Like the complement fixation, the buffered antigen test is more specific than seroagglutination. On the other hand, with such an antigen concentration the test lacks sensitivity. In the second part the authors compare the results obtained by these three tests--but this time utilizing a buffered brucella antigen of cellular concentration of approximately 5%--on bovines and ovines whose infection had been determined bacteriologically. The authors have established, under these conditions, that the buffered brucella antigen test allows the screening of a greater number of infected animals than does the SAW or even the FC. Both for bovines as well as ovines, the agreement between SAW and EAT equals 89%; betueen FC and EAT it reaches 93%; in case of disagreement it is always the EAT which is positive.", "contents": "[Serologic diagnosis of bovine and ovine brucellosis by a buffered antigen test]. In the first part the authors compare the results of the test effected by means of a buffered antigen (EAT) whose cellular concentration was about 10%, with those of slow seroagglutination (SAW) and complement fixation (FC). Like the complement fixation, the buffered antigen test is more specific than seroagglutination. On the other hand, with such an antigen concentration the test lacks sensitivity. In the second part the authors compare the results obtained by these three tests--but this time utilizing a buffered brucella antigen of cellular concentration of approximately 5%--on bovines and ovines whose infection had been determined bacteriologically. The authors have established, under these conditions, that the buffered brucella antigen test allows the screening of a greater number of infected animals than does the SAW or even the FC. Both for bovines as well as ovines, the agreement between SAW and EAT equals 89%; betueen FC and EAT it reaches 93%; in case of disagreement it is always the EAT which is positive."} {"id": "PMID:1261734", "title": "[Lymphoblastic transformation by fractions of Brucella in patients having had brucellosis and subjects vaccinated by the vaccine PI].", "content": "Two fractions of brucella, examined elsewhere for their vaccinal properties (P.I. and 4A) have been used in lymphoblastic stimulation tests with lymphocytes of subjects infected by brucellosis and subjects vaccinated with P.I. This investigation attempted to show the importance of cellular immunity in brucellosis and to deduce a valid protection test. The two fractions do not possess non-specific mitogenic activity for human lymphocytes, but they stimulate specifically the sensitized lymphocytes. Subjects formerly or recently infected with brucellosis present constantly positive tests with sometimes a very high stimulation index. Vaccinated subjects have a lower stimulation index which is, however, significant in practically each case. The P.I. fraction gives the most constant results in the two categories of subjects; 4A appears to be much less active. The divergence between the protection rates conferred by 4A to animals and the weak activity of this same fraction in stimulation tests of human lymphocytes raises, on the one hand, the problem of the relation between protection and cellular immunity and, on the other hand, the utilization of animal models for the investigation of human vaccines.", "contents": "[Lymphoblastic transformation by fractions of Brucella in patients having had brucellosis and subjects vaccinated by the vaccine PI]. Two fractions of brucella, examined elsewhere for their vaccinal properties (P.I. and 4A) have been used in lymphoblastic stimulation tests with lymphocytes of subjects infected by brucellosis and subjects vaccinated with P.I. This investigation attempted to show the importance of cellular immunity in brucellosis and to deduce a valid protection test. The two fractions do not possess non-specific mitogenic activity for human lymphocytes, but they stimulate specifically the sensitized lymphocytes. Subjects formerly or recently infected with brucellosis present constantly positive tests with sometimes a very high stimulation index. Vaccinated subjects have a lower stimulation index which is, however, significant in practically each case. The P.I. fraction gives the most constant results in the two categories of subjects; 4A appears to be much less active. The divergence between the protection rates conferred by 4A to animals and the weak activity of this same fraction in stimulation tests of human lymphocytes raises, on the one hand, the problem of the relation between protection and cellular immunity and, on the other hand, the utilization of animal models for the investigation of human vaccines."} {"id": "PMID:1261735", "title": "A potency assay for brucella allergens in guinea pigs.", "content": "In the development of a biological potency assay for brucella allergens by skin testing of guinea pigs, it was observed that the delayed hypersensitivity reactions to a given dose depended upon (1) the method of sensitization of the guinea pigs, (2) the time interval between sensitization and skin test and (3) the total of allergen given per animal. Data illustrating these factors are presented and a method for titrating allergens is recommended.", "contents": "A potency assay for brucella allergens in guinea pigs. In the development of a biological potency assay for brucella allergens by skin testing of guinea pigs, it was observed that the delayed hypersensitivity reactions to a given dose depended upon (1) the method of sensitization of the guinea pigs, (2) the time interval between sensitization and skin test and (3) the total of allergen given per animal. Data illustrating these factors are presented and a method for titrating allergens is recommended."} {"id": "PMID:1261736", "title": "[A new allergen for the determination of ovine brucellosis].", "content": "The authors report on the experimental use of an allergen, prepared by a special method, for the detection of brucellosis in both infected and non-infected sheep. The best method is the intradermal injection into the eyelid of 0.5 ml and the best time for reading the reaction is between 48 and 72 hrs after inoculation. The allergen proved more sensitive than the serum-agglutination test on infected sheep, and extremely specific, since all tests on non-infected sheep were negative and induced neither agglutinin production nor allergic sensitization.", "contents": "[A new allergen for the determination of ovine brucellosis]. The authors report on the experimental use of an allergen, prepared by a special method, for the detection of brucellosis in both infected and non-infected sheep. The best method is the intradermal injection into the eyelid of 0.5 ml and the best time for reading the reaction is between 48 and 72 hrs after inoculation. The allergen proved more sensitive than the serum-agglutination test on infected sheep, and extremely specific, since all tests on non-infected sheep were negative and induced neither agglutinin production nor allergic sensitization."} {"id": "PMID:1261738", "title": "[Antigen therapy in chronic brucellosis].", "content": "The different forms of chronic brucellosis have been improved and well stabilized in the proportion of 75% by repeated injections of a vaccine consisting of suspensions of heat-killed B. melitensis. The vaccine should be used in a series of 8 subcutaneous injections, in increasing doses, at the rate of 2 injections a week. To obtain good results it is necessary to give an average of 3 to 4 series of injections, with a two months' interval between each series. After the 2nd series a distinct decrease of the patient's reactions to retarded hypersensitivity tests are generally observed. The most favourable results are obtained in cases of common subjective syndrome with physical and psychical asthenia.", "contents": "[Antigen therapy in chronic brucellosis]. The different forms of chronic brucellosis have been improved and well stabilized in the proportion of 75% by repeated injections of a vaccine consisting of suspensions of heat-killed B. melitensis. The vaccine should be used in a series of 8 subcutaneous injections, in increasing doses, at the rate of 2 injections a week. To obtain good results it is necessary to give an average of 3 to 4 series of injections, with a two months' interval between each series. After the 2nd series a distinct decrease of the patient's reactions to retarded hypersensitivity tests are generally observed. The most favourable results are obtained in cases of common subjective syndrome with physical and psychical asthenia."} {"id": "PMID:1261739", "title": "Canine brucellosis: newer knowledge.", "content": "Canine brucellosis is a worldwide disease of dogs characterized prinicpally by abortions in females and epididymitis and infertility in males. It originally was observed in the USA, but recently it has been discovered in Japan, Mexico, Peru, Germany and, possibly, in Brazil. It affects dogs of all breeds and has been diagnosed in breeding kennels and in stray dogs. Several human cases have occurred, with 6 being accidental infections by laboratory personnel. B. canis, like B. ovis, is naturally mucoid, lacking \"S\" antigens. Serological tests therefore are not appropriate to classification. On the basis of manometric technics, B. canis is similar to B. suis; nevertheless the host range excludes swine. Agreement on its taxonomic status is not universal, although it has been provisionally accepted by the Subcommittee on Taxonomy of Brucella as a new species. A brief review of salient characteristics of B. canis was presented, however the principal discussion focused on recently observed aspects of the immunopathogenesis of male infertility and reported the development of a rapid slide agglutination test, using as antigen a concentrated and stained (Rose Bengal dye) suspension of B. ovis.", "contents": "Canine brucellosis: newer knowledge. Canine brucellosis is a worldwide disease of dogs characterized prinicpally by abortions in females and epididymitis and infertility in males. It originally was observed in the USA, but recently it has been discovered in Japan, Mexico, Peru, Germany and, possibly, in Brazil. It affects dogs of all breeds and has been diagnosed in breeding kennels and in stray dogs. Several human cases have occurred, with 6 being accidental infections by laboratory personnel. B. canis, like B. ovis, is naturally mucoid, lacking \"S\" antigens. Serological tests therefore are not appropriate to classification. On the basis of manometric technics, B. canis is similar to B. suis; nevertheless the host range excludes swine. Agreement on its taxonomic status is not universal, although it has been provisionally accepted by the Subcommittee on Taxonomy of Brucella as a new species. A brief review of salient characteristics of B. canis was presented, however the principal discussion focused on recently observed aspects of the immunopathogenesis of male infertility and reported the development of a rapid slide agglutination test, using as antigen a concentrated and stained (Rose Bengal dye) suspension of B. ovis."} {"id": "PMID:1261740", "title": "[Clinical and epizootiological aspects of bovine, caprine, and ovine brucellosis in Greece].", "content": "The author reports on an investigation, in Greece, of the clinical and epizootiological aspects of bovine, caprine and ovine brucellosis. These three types of brucellosis are found in the abortive and latent forms. The abortive form is revealed by contagious abortions whose frequency depends principally on the composition of the animal population of the farm; during its evolution, numerous very high positive serological reactions are observed. It involves many complications, causes heavy economic losses and is passed on to a great number of breeders. The latent form is accompanied by chronic manifestations, but passes unnoticed for the most part and is discovered only by serological tests during a period of suspect abortions of human cases of brucellosis. There are fewer of these cases then when the disease evolves in the region in the abortive form. The latent form contributes to the multiplication of centres of infection (1) when apparently uninfected female animals coming from farms contaminated with the latent form are introduced into healthy herds, (2) when the latent form changes into the abortive form after the introduction of healthy female animals into farms contaminated with this form. Furthermore, because of its inapparent evolution, it is a constant danger to rural populations. Bovine brucellosis has been observed in 16 of the 52 departments in the country, and caprine and ovine brucellosis in 21. The proportion of infection throughout the bovine, caprine and ovine herds of the 38 departments in which the investigation was made is approximately 4.70, 1.29, and 0.33 per thousand, respectively. The usual pathogenic agent of bovine brucellosis is Br. abortus; Br. abortus resistant to thionin is found less frequently and Br. melitensis only occasionally. The usual pathogenic agent of caprine and ovine brucellosis is Br. melitensis; Br. intermedia is less frequent and Br. abortus is found only rarely. Four Tables show the clinical investigation of 150 bovine abortions of brucellic origin and observations on the sanitary conditions of 22 cattle-sheds and herds infected with abortive or latent brucellosis. The author concludes in favour of the necessity of medical prophylactic measures and the strict application of sanitary prophylactic measures. In general, new animals should not be introduced into farms but when this is necessary the animal should not be considered free from brucellosis simply because of negative serological reactions. The best policy, in this case, is to repopulate entire farms negative to serological tests by seronegative animals coming also from entirely negative farms.", "contents": "[Clinical and epizootiological aspects of bovine, caprine, and ovine brucellosis in Greece]. The author reports on an investigation, in Greece, of the clinical and epizootiological aspects of bovine, caprine and ovine brucellosis. These three types of brucellosis are found in the abortive and latent forms. The abortive form is revealed by contagious abortions whose frequency depends principally on the composition of the animal population of the farm; during its evolution, numerous very high positive serological reactions are observed. It involves many complications, causes heavy economic losses and is passed on to a great number of breeders. The latent form is accompanied by chronic manifestations, but passes unnoticed for the most part and is discovered only by serological tests during a period of suspect abortions of human cases of brucellosis. There are fewer of these cases then when the disease evolves in the region in the abortive form. The latent form contributes to the multiplication of centres of infection (1) when apparently uninfected female animals coming from farms contaminated with the latent form are introduced into healthy herds, (2) when the latent form changes into the abortive form after the introduction of healthy female animals into farms contaminated with this form. Furthermore, because of its inapparent evolution, it is a constant danger to rural populations. Bovine brucellosis has been observed in 16 of the 52 departments in the country, and caprine and ovine brucellosis in 21. The proportion of infection throughout the bovine, caprine and ovine herds of the 38 departments in which the investigation was made is approximately 4.70, 1.29, and 0.33 per thousand, respectively. The usual pathogenic agent of bovine brucellosis is Br. abortus; Br. abortus resistant to thionin is found less frequently and Br. melitensis only occasionally. The usual pathogenic agent of caprine and ovine brucellosis is Br. melitensis; Br. intermedia is less frequent and Br. abortus is found only rarely. Four Tables show the clinical investigation of 150 bovine abortions of brucellic origin and observations on the sanitary conditions of 22 cattle-sheds and herds infected with abortive or latent brucellosis. The author concludes in favour of the necessity of medical prophylactic measures and the strict application of sanitary prophylactic measures. In general, new animals should not be introduced into farms but when this is necessary the animal should not be considered free from brucellosis simply because of negative serological reactions. The best policy, in this case, is to repopulate entire farms negative to serological tests by seronegative animals coming also from entirely negative farms."} {"id": "PMID:1261741", "title": "[Brucellic mammitis in sows].", "content": "In a herd of pigs, 31% presented serological reactions positive or doubtful to brucellic infection; in 15% of the sows the mammary glands were swollen and purulent; the retromammary ganglions were enlarged and hemorrhagic. Bacteriological examination of the pus of mammary lesions showed the presence of Brucella suis, which confirmed the diagnosis of brucellic mammitis in the sows. The purulent discharge of the mammary lesions, diluted with physiological serum, agglutinated with the antibrucellic serum and this fact may constitute, together with other means of investigation, a method of rapid diagnosis.", "contents": "[Brucellic mammitis in sows]. In a herd of pigs, 31% presented serological reactions positive or doubtful to brucellic infection; in 15% of the sows the mammary glands were swollen and purulent; the retromammary ganglions were enlarged and hemorrhagic. Bacteriological examination of the pus of mammary lesions showed the presence of Brucella suis, which confirmed the diagnosis of brucellic mammitis in the sows. The purulent discharge of the mammary lesions, diluted with physiological serum, agglutinated with the antibrucellic serum and this fact may constitute, together with other means of investigation, a method of rapid diagnosis."} {"id": "PMID:1261742", "title": "[Bovine brucellosis in Morocco].", "content": "A serological investigation was carried out during 1974 on the dairy cattle of Morocco. 20,000 serums from all the different provinces were controlled simultaneously by the slow sero-agglutination test and complement fixation. The centre of brucellic infection, which involves for the most part imported breeds, was found to be in the region of Casablanca (27%), Rabat, Sal\u00e9, F\u00e8s and Meknes.", "contents": "[Bovine brucellosis in Morocco]. A serological investigation was carried out during 1974 on the dairy cattle of Morocco. 20,000 serums from all the different provinces were controlled simultaneously by the slow sero-agglutination test and complement fixation. The centre of brucellic infection, which involves for the most part imported breeds, was found to be in the region of Casablanca (27%), Rabat, Sal\u00e9, F\u00e8s and Meknes."} {"id": "PMID:1261743", "title": "Recommendations for the description of species and biotypes of the genus Brucella.", "content": "The properties of the genus Brucella are summarized and recommendations made for the definition of species and biotypes within the genus. In the first instance it is recommended that the classification of an organism as a member of the genus should be based on the following criteria: gramnegative coccobacillary morphology, a G + C content for the DNA of 56-58 moles %, a minimum of 90% homology with the DNA of reference strains in hybridization tests, disk electrophoretograms of acid-phenol soluble proteins of identical pattern to reference strains, a cytochrome C absorption spectrum with absorption maxima between 522-530 nm and 552-560 nm, extensive serological cross-reactions of intra-cellular antigens with those of reference strains. Supporting evidence is obtained from cultural, biochemical and pathogenic properties, although variations in these occur within the genus. Subdivision into species is dependent upon principal natural host, oxidative metabolic pattern and phage sensitivity. Classification into biotypes is dependent upon CO2 requirement, H2S production, dye sensitivity and reaction with monospecific antisera to A and M antigens. It is recommended that any organism proposed as a new member of the genus should have characters which approximate the ranges quoted. In all cases comparisons should be made with the established reference/neotype strains.", "contents": "Recommendations for the description of species and biotypes of the genus Brucella. The properties of the genus Brucella are summarized and recommendations made for the definition of species and biotypes within the genus. In the first instance it is recommended that the classification of an organism as a member of the genus should be based on the following criteria: gramnegative coccobacillary morphology, a G + C content for the DNA of 56-58 moles %, a minimum of 90% homology with the DNA of reference strains in hybridization tests, disk electrophoretograms of acid-phenol soluble proteins of identical pattern to reference strains, a cytochrome C absorption spectrum with absorption maxima between 522-530 nm and 552-560 nm, extensive serological cross-reactions of intra-cellular antigens with those of reference strains. Supporting evidence is obtained from cultural, biochemical and pathogenic properties, although variations in these occur within the genus. Subdivision into species is dependent upon principal natural host, oxidative metabolic pattern and phage sensitivity. Classification into biotypes is dependent upon CO2 requirement, H2S production, dye sensitivity and reaction with monospecific antisera to A and M antigens. It is recommended that any organism proposed as a new member of the genus should have characters which approximate the ranges quoted. In all cases comparisons should be made with the established reference/neotype strains."} {"id": "PMID:1261744", "title": "[Clinical and epidemiological aspects of bovine brucellosis in tropical Africa].", "content": "Bovine brucellosis, in the tropical regions of Africa, is very different, both clinically and epidermiologically, from that observed in temperate zones. From the clinical point of view, abortion is rare and extra-genital lesions (hygromas and abscesses) are frequent. From the epidemiological point of view, the rate of infection is low and the disease has very little tendency to spread. The reason for these differences may be explained by climatic conditions (temperature, insolation, humidity) as well as by breeding conditions (principally nomadic or transhumant breeding). Where climatic and breeding conditions resemble those of intensive breeding in temperate zones the clinical and epidemiological aspects tend towards similarity with the usual form of bovine brucellosis.", "contents": "[Clinical and epidemiological aspects of bovine brucellosis in tropical Africa]. Bovine brucellosis, in the tropical regions of Africa, is very different, both clinically and epidermiologically, from that observed in temperate zones. From the clinical point of view, abortion is rare and extra-genital lesions (hygromas and abscesses) are frequent. From the epidemiological point of view, the rate of infection is low and the disease has very little tendency to spread. The reason for these differences may be explained by climatic conditions (temperature, insolation, humidity) as well as by breeding conditions (principally nomadic or transhumant breeding). Where climatic and breeding conditions resemble those of intensive breeding in temperate zones the clinical and epidemiological aspects tend towards similarity with the usual form of bovine brucellosis."} {"id": "PMID:1261745", "title": "[Effect of temperature on preservation of brucella vaccines].", "content": "In the case of B.19 vaccine, the test of seven days conservation at 37 degrees C does not provide any indication of the long-term conservation of this type of vaccine. The variable results are difficult to interpret, except in extreme cases where the tested vaccine has deteriorated. If this test permits to disclose the deficiencies of lyophilization, it does not permit the stability of this strain to be foreseen. Heating for 30 days at 37 degrees C gives better results, without showing any satisfactory correlation with the duration of validity of the vaccine. Further trials need to be undertaken to try to establish a correlation between an accelerated ageing test and the duration of validity of B.19 vaccine.", "contents": "[Effect of temperature on preservation of brucella vaccines]. In the case of B.19 vaccine, the test of seven days conservation at 37 degrees C does not provide any indication of the long-term conservation of this type of vaccine. The variable results are difficult to interpret, except in extreme cases where the tested vaccine has deteriorated. If this test permits to disclose the deficiencies of lyophilization, it does not permit the stability of this strain to be foreseen. Heating for 30 days at 37 degrees C gives better results, without showing any satisfactory correlation with the duration of validity of the vaccine. Further trials need to be undertaken to try to establish a correlation between an accelerated ageing test and the duration of validity of B.19 vaccine."} {"id": "PMID:1261746", "title": "[The place of the principal antibrucellic vaccines in prophylaxis].", "content": "This communication is intended to clarify the conditions and methods of the utilization in France of the antibrucellic vaccines in accordance with regulations covering the prevention of brucellosis in animals. It should be noted that it is only within the framework of the prophylaxis of bovine brucellosis that the problem of the utilization of these vaccines will be investigated. Since the objective is the complete eradication of the disease, measure taken within the framework of the regulations are essentially aimed at eliminating contaminated animals; these are for the most part sanitary measures. However, this type of prophylaxis cannot yet be undertaken simply by the application of the regulations because of the lack of financial support accorded by the State. For this reason, as well as because the high rate of infection in certain regions would make the application of these measures very difficult for the farmers, it seemed necessary to utilize vaccines to ensure protection and to attain, in a preparatory phase, a decrease in the rate of infection.", "contents": "[The place of the principal antibrucellic vaccines in prophylaxis]. This communication is intended to clarify the conditions and methods of the utilization in France of the antibrucellic vaccines in accordance with regulations covering the prevention of brucellosis in animals. It should be noted that it is only within the framework of the prophylaxis of bovine brucellosis that the problem of the utilization of these vaccines will be investigated. Since the objective is the complete eradication of the disease, measure taken within the framework of the regulations are essentially aimed at eliminating contaminated animals; these are for the most part sanitary measures. However, this type of prophylaxis cannot yet be undertaken simply by the application of the regulations because of the lack of financial support accorded by the State. For this reason, as well as because the high rate of infection in certain regions would make the application of these measures very difficult for the farmers, it seemed necessary to utilize vaccines to ensure protection and to attain, in a preparatory phase, a decrease in the rate of infection."} {"id": "PMID:1261747", "title": "[Control and eradication of ovine and caprine brucellosis in Italy].", "content": "The prevention of ovine and caprine brucellosis in Italy is carried out in accordance with Regulation No 33 of 23 January 1968 and with Government Decree of 4 June 1968. The Regulation also provides in addition to sanitary measures, the vaccination of all livestock aged from 3 to 7 months with strain Rev. 1 of Br. melitensis. From the last trimester of 1968 until the end of 1974 3489514 young animals were vaccinated, which corresponds approximately to 50% of the animals today in the zones where the \"revisation\" was undertaken. An important decrease in the number of abortions was observed, with many epizootical advantages. During the same period a considerable decrease in human cases of brucellosis was observed; from the 19300 cases announced from 1965 to 1968 (yearly average: 4825) the figure fell to 18988 cases for the period 1969-1974 (yearly average: 3164).", "contents": "[Control and eradication of ovine and caprine brucellosis in Italy]. The prevention of ovine and caprine brucellosis in Italy is carried out in accordance with Regulation No 33 of 23 January 1968 and with Government Decree of 4 June 1968. The Regulation also provides in addition to sanitary measures, the vaccination of all livestock aged from 3 to 7 months with strain Rev. 1 of Br. melitensis. From the last trimester of 1968 until the end of 1974 3489514 young animals were vaccinated, which corresponds approximately to 50% of the animals today in the zones where the \"revisation\" was undertaken. An important decrease in the number of abortions was observed, with many epizootical advantages. During the same period a considerable decrease in human cases of brucellosis was observed; from the 19300 cases announced from 1965 to 1968 (yearly average: 4825) the figure fell to 18988 cases for the period 1969-1974 (yearly average: 3164)."} {"id": "PMID:1261748", "title": "[Preparation and testing of different antibrucellic vaccines].", "content": "From a highly virulent Brucella melitensis strain of human origin, different vaccines of good antigenic quality are obtained, ranging from the very agglutinogenic oily type vaccine to the totally non-agglutinogenic oily type vaccine. The non-agglutinogenic vaccine is obtained by an original method consisting of submission of the original brucella to several subcultures in the presence of a small quantity of antiserum and clonal selection of a population. The strain finally selected is totally non-agglutinogenic and its biochemical characteristics are hardly different from those of the original strain; it conserves good antigenicity and compares favourably with the other non-agglutinogenic vaccines tested.", "contents": "[Preparation and testing of different antibrucellic vaccines]. From a highly virulent Brucella melitensis strain of human origin, different vaccines of good antigenic quality are obtained, ranging from the very agglutinogenic oily type vaccine to the totally non-agglutinogenic oily type vaccine. The non-agglutinogenic vaccine is obtained by an original method consisting of submission of the original brucella to several subcultures in the presence of a small quantity of antiserum and clonal selection of a population. The strain finally selected is totally non-agglutinogenic and its biochemical characteristics are hardly different from those of the original strain; it conserves good antigenicity and compares favourably with the other non-agglutinogenic vaccines tested."} {"id": "PMID:1261749", "title": "Properties of some new Brucella phage isolates; evidence for lysogeny within the genus.", "content": "A number of phages were isolated from Brucella abortus strains showing atypical phage sensitivity patterns. The phages, designated the Firenze group, were all similar in morphology, host range general properties. They were lytic for smooth Brucella abortus, Br. neotomae and Br. suis, but not for Br. melitensis strains. They were serologically distinct from phages of the Tbilisi and M51-S708-Weybridge groups and also differed from these in plaque morphology and physical and chemical stability. The parent brucella strains although smooth were resistant to lysis by their own phages or by the other available brucella phages. Their general properties suggested a lysogenic state.", "contents": "Properties of some new Brucella phage isolates; evidence for lysogeny within the genus. A number of phages were isolated from Brucella abortus strains showing atypical phage sensitivity patterns. The phages, designated the Firenze group, were all similar in morphology, host range general properties. They were lytic for smooth Brucella abortus, Br. neotomae and Br. suis, but not for Br. melitensis strains. They were serologically distinct from phages of the Tbilisi and M51-S708-Weybridge groups and also differed from these in plaque morphology and physical and chemical stability. The parent brucella strains although smooth were resistant to lysis by their own phages or by the other available brucella phages. Their general properties suggested a lysogenic state."} {"id": "PMID:1261750", "title": "[Identification of Brucella of human origin, isolated in France].", "content": "28 strains of human origin, isolated in France, have been examined by the methods recommended by the International Committee on Nomenclature, Sub-Committee on Taxonomy of the genus Brucella including oxidative metabolism and phage typing. Their characteristics correspond to those which allow to define B. melitensis (22 strains) and B. abortus (6 strains). The B. melitensis strains are divided as follows: 11 belong to biotype 1, 6 to biotype 2 and 5 to biotype 3. Among the 6 strains of B. abortus, 4 belong to biotype 1, one to biotype 2 and one to biotype 3. For these two species of brucella, the oxydative spectre established in relation to 12 substrates may be represented graphically by a metabolic profile peculiar to the bacterial species and not to its biotype nor to the nature of the human or animal reservoir.", "contents": "[Identification of Brucella of human origin, isolated in France]. 28 strains of human origin, isolated in France, have been examined by the methods recommended by the International Committee on Nomenclature, Sub-Committee on Taxonomy of the genus Brucella including oxidative metabolism and phage typing. Their characteristics correspond to those which allow to define B. melitensis (22 strains) and B. abortus (6 strains). The B. melitensis strains are divided as follows: 11 belong to biotype 1, 6 to biotype 2 and 5 to biotype 3. Among the 6 strains of B. abortus, 4 belong to biotype 1, one to biotype 2 and one to biotype 3. For these two species of brucella, the oxydative spectre established in relation to 12 substrates may be represented graphically by a metabolic profile peculiar to the bacterial species and not to its biotype nor to the nature of the human or animal reservoir."} {"id": "PMID:1261751", "title": "Studies of Brucella lipopolysaccharide.", "content": "Brucella endotoxin differs from other gramnegative endotoxins in that it is recovered in the phenol phase rather than the aqueous phase of the Westphal hot phenol water procedure. This was the first described from this laboratory by Redfearn (1960) with phenol-killed smooth B. abortus and B. melitensis and has since been confirmed by others. Preliminary extraction of brucella cells with acetone, as called for in the original Westphal procedure, was followed by Renoux et al. (1973) who reported that the aqueous phase lacked endotoxic activity and the phenol phase had very low toxicity. In order to test the hypothesis that prior acetone extraction removes lipid A, we have repeated the Redfearn procedure with acetone extracted cells and have confirmed that the major portion of the endotoxic activity resides in the phenol phase. Acetone treatment does not remove the lipid A believed to be responsible for mouse lethality as well as necrotizing activity in guinea pig and rabbit skin. Preparations of brucella endotoxin (lipopolysaccharide) contain varying amounts of polypeptide some of which is tightly bound. The dermal response of sensitized guinea pigs to brucella LPS was shown to be a combination of reactions comprising those due to (1) innate toxicity of lipid A, (2) antibody mediated reactions due to polysaccharide portion of the molecule and (3) delayed hypersensitivity due to polypeptide portion of the molecule.", "contents": "Studies of Brucella lipopolysaccharide. Brucella endotoxin differs from other gramnegative endotoxins in that it is recovered in the phenol phase rather than the aqueous phase of the Westphal hot phenol water procedure. This was the first described from this laboratory by Redfearn (1960) with phenol-killed smooth B. abortus and B. melitensis and has since been confirmed by others. Preliminary extraction of brucella cells with acetone, as called for in the original Westphal procedure, was followed by Renoux et al. (1973) who reported that the aqueous phase lacked endotoxic activity and the phenol phase had very low toxicity. In order to test the hypothesis that prior acetone extraction removes lipid A, we have repeated the Redfearn procedure with acetone extracted cells and have confirmed that the major portion of the endotoxic activity resides in the phenol phase. Acetone treatment does not remove the lipid A believed to be responsible for mouse lethality as well as necrotizing activity in guinea pig and rabbit skin. Preparations of brucella endotoxin (lipopolysaccharide) contain varying amounts of polypeptide some of which is tightly bound. The dermal response of sensitized guinea pigs to brucella LPS was shown to be a combination of reactions comprising those due to (1) innate toxicity of lipid A, (2) antibody mediated reactions due to polysaccharide portion of the molecule and (3) delayed hypersensitivity due to polypeptide portion of the molecule."} {"id": "PMID:1261752", "title": "[Structure and constituents of Brucella. Characterization and biological properties of the fractions].", "content": "The analysis of the components of a bacterium may be envisaged from the biological aspect (fractionation), the ultrastructural aspect (staining of the structures examined electron-microscopically), and the biological aspect (measure of an activity). In this report we attempt to examine the components of brucella from all three aspects simultaneously. The brucella envelopes have the same ultrastructure as that of gramnegative bacteria: outer membrane, thick stratum or peptidoglycane, periplasmic space, cytoplasmic membrane. The outer membrane of brucella in phase S contains many types of polysaccharides: (1) the lipopolysaccharide (LPS) (S) and polysaccharide B are solubilized by the phenol-uater and ether-water methods, by trichloracetic acid (TCA), by heated sodium dodecyl-sulfate (SDS). The exact localization of polysaccharide B is not known; by the phenol-water extraction method, the LPS (S) in its toxic form (endotoxin) passes in solution into the phenol phase, unlike the endotoxin of enterobacteria, which passes into the aqueous phase. In addition to its toxicity, this LPS (S) is responsible for reactions of immediate hypersensitivity as well as serological reactions towards the standard antigen. It presents A + M antigenic sites; (2) one or more of the polysaccharides remains unsolubilized by the ether-water method, but solubilized by heated SDS; (3) a polysaccharide is linked to peptidoglycane. The structure of the outer membrane of the brucella in phase R is analogous to that of LPS, carrying antigen R, characteristic of these strains. This antigen may be utilized for the serological diagnosis of infections due to brucella R (B. ovis) or vaccinations by a vaccine in phase R. The peptidoglycane fraction extracted by the heated SDS has a more complex structure than that of E. coli: it consists of a supplementary outer layer containing amino acids and polysaccharides. This fraction has a vaccinal activity. A soluble protein fraction, without organized structure, no doubt of cytoplasmic origin, may be extracted by a cold saline solution. This fraction, known as \"brucelline\", reveals delayed hypersensitivity when injected intradermally. The biological activity of the other structures (periplasm, cytoplasmic membrane, ribosomes...) is not known. Biological activities have been attributed to fractions, but since these are badly defined from the structural point of view it is difficult to determine the connection between activities and structures.", "contents": "[Structure and constituents of Brucella. Characterization and biological properties of the fractions]. The analysis of the components of a bacterium may be envisaged from the biological aspect (fractionation), the ultrastructural aspect (staining of the structures examined electron-microscopically), and the biological aspect (measure of an activity). In this report we attempt to examine the components of brucella from all three aspects simultaneously. The brucella envelopes have the same ultrastructure as that of gramnegative bacteria: outer membrane, thick stratum or peptidoglycane, periplasmic space, cytoplasmic membrane. The outer membrane of brucella in phase S contains many types of polysaccharides: (1) the lipopolysaccharide (LPS) (S) and polysaccharide B are solubilized by the phenol-uater and ether-water methods, by trichloracetic acid (TCA), by heated sodium dodecyl-sulfate (SDS). The exact localization of polysaccharide B is not known; by the phenol-water extraction method, the LPS (S) in its toxic form (endotoxin) passes in solution into the phenol phase, unlike the endotoxin of enterobacteria, which passes into the aqueous phase. In addition to its toxicity, this LPS (S) is responsible for reactions of immediate hypersensitivity as well as serological reactions towards the standard antigen. It presents A + M antigenic sites; (2) one or more of the polysaccharides remains unsolubilized by the ether-water method, but solubilized by heated SDS; (3) a polysaccharide is linked to peptidoglycane. The structure of the outer membrane of the brucella in phase R is analogous to that of LPS, carrying antigen R, characteristic of these strains. This antigen may be utilized for the serological diagnosis of infections due to brucella R (B. ovis) or vaccinations by a vaccine in phase R. The peptidoglycane fraction extracted by the heated SDS has a more complex structure than that of E. coli: it consists of a supplementary outer layer containing amino acids and polysaccharides. This fraction has a vaccinal activity. A soluble protein fraction, without organized structure, no doubt of cytoplasmic origin, may be extracted by a cold saline solution. This fraction, known as \"brucelline\", reveals delayed hypersensitivity when injected intradermally. The biological activity of the other structures (periplasm, cytoplasmic membrane, ribosomes...) is not known. Biological activities have been attributed to fractions, but since these are badly defined from the structural point of view it is difficult to determine the connection between activities and structures."} {"id": "PMID:1261753", "title": "Brucellosis as a world problem.", "content": "Brucellosis is one of the most widespread and economically the most ravaging of zoonoses. The occurrence of the acute, often incapacitating infection in man caused by Brucella melitensis usually coincides with occurrence of the infection in sheep and goats. Well-known foci of this infection have been identified in the Mediterranean basin, Central Asia and Latin America. Recent investigations in parts of Africa and India have shown that the infection is much more widespread than was previously suspected and that more foci remain to be discovered by the application of laboratory methods in epidemiological investigations. Bovine infection has a wider distribution and is more important than infection of sheep and goats as far as economic losses are concerned. Although the infection has been reduced by control measures to a low level of incidence in some countries of Europe and North America, its incidence in other parts of the world has actually increased because of emphasis on increased animal production and aggregation under poor hygienic conditions. This is particularly the case with dairy production units which have developed around rapidly growing urban centres in many developing countries. Although human infection with B. abortus may be mild, it can cause troublesome and intractable illness. The economic ravages of bovine brucellosis are tremendous and the losses in Latin America and the USA alone have been estimated by their respective governments to be 700 million dollars annually. The world figure must be truly staggering. Swine brucellosis is largely a problem of the Americas although a few foci have recently been discovered in other parts of the world, notably in Europe and Southern Asia. In the Americas, swine infection is second only to bovine brucellosis in its economic importance. A large number of human cases of B. suis infection are detected every year in the endemic areas. Other forms of brucellosis, e.g. B. canis in dogs and B. suis, biotype 4 in reindeer, have a limited distribution and are responsible for only sporadic human infections. B. ovis of sheep is more widespread but is generally confined to sheep. Annexes 1 and 2 show the reported incidence of brucellosis in man and animals. However, the officially reported data are generally incomplete and the actual incidence must in most cases be much higher than is shown in these tables. FAO and WHO have been assisting countries in which brucellosis is endemic by organizing control measures, providing training and reference materials, and by focusing coordinated research on problems which arise in these programmes. Some of the highlights of this work are outlined in the following paragraphs.", "contents": "Brucellosis as a world problem. Brucellosis is one of the most widespread and economically the most ravaging of zoonoses. The occurrence of the acute, often incapacitating infection in man caused by Brucella melitensis usually coincides with occurrence of the infection in sheep and goats. Well-known foci of this infection have been identified in the Mediterranean basin, Central Asia and Latin America. Recent investigations in parts of Africa and India have shown that the infection is much more widespread than was previously suspected and that more foci remain to be discovered by the application of laboratory methods in epidemiological investigations. Bovine infection has a wider distribution and is more important than infection of sheep and goats as far as economic losses are concerned. Although the infection has been reduced by control measures to a low level of incidence in some countries of Europe and North America, its incidence in other parts of the world has actually increased because of emphasis on increased animal production and aggregation under poor hygienic conditions. This is particularly the case with dairy production units which have developed around rapidly growing urban centres in many developing countries. Although human infection with B. abortus may be mild, it can cause troublesome and intractable illness. The economic ravages of bovine brucellosis are tremendous and the losses in Latin America and the USA alone have been estimated by their respective governments to be 700 million dollars annually. The world figure must be truly staggering. Swine brucellosis is largely a problem of the Americas although a few foci have recently been discovered in other parts of the world, notably in Europe and Southern Asia. In the Americas, swine infection is second only to bovine brucellosis in its economic importance. A large number of human cases of B. suis infection are detected every year in the endemic areas. Other forms of brucellosis, e.g. B. canis in dogs and B. suis, biotype 4 in reindeer, have a limited distribution and are responsible for only sporadic human infections. B. ovis of sheep is more widespread but is generally confined to sheep. Annexes 1 and 2 show the reported incidence of brucellosis in man and animals. However, the officially reported data are generally incomplete and the actual incidence must in most cases be much higher than is shown in these tables. FAO and WHO have been assisting countries in which brucellosis is endemic by organizing control measures, providing training and reference materials, and by focusing coordinated research on problems which arise in these programmes. Some of the highlights of this work are outlined in the following paragraphs."} {"id": "PMID:1261754", "title": "[Chemical fractionation of Brucella melitensis and the immunizing properties of a new fraction].", "content": "A complex phenol-insoluble fraction (fraction P.I.) extracted from Brucella melitensis presents immunizing properties already described by the authors. This fraction contains peptidoglycane whose immuno-adjuvant properties are known in numerous bacterial species. More precise fractionation was carried out to determine if the properties observed after injection of P.I. are in fact specific or on the contrary due to peptidoglycane action. By chemical and enzymatic treatments, 90% of the P.I. are eliminated, leaving a 4A fraction having the same properties as P.I. and having the advantage of providing better protection. This protection specific to genus Brucella and slow in appearing, is not due to peptidoglycane. The 4A fraction consists essentially of peptidoglycane linked covalently with a lipoprotein and proteins of weak molecular weight. All attempts at more precise fractionation have until now led to the loss of biological activity.", "contents": "[Chemical fractionation of Brucella melitensis and the immunizing properties of a new fraction]. A complex phenol-insoluble fraction (fraction P.I.) extracted from Brucella melitensis presents immunizing properties already described by the authors. This fraction contains peptidoglycane whose immuno-adjuvant properties are known in numerous bacterial species. More precise fractionation was carried out to determine if the properties observed after injection of P.I. are in fact specific or on the contrary due to peptidoglycane action. By chemical and enzymatic treatments, 90% of the P.I. are eliminated, leaving a 4A fraction having the same properties as P.I. and having the advantage of providing better protection. This protection specific to genus Brucella and slow in appearing, is not due to peptidoglycane. The 4A fraction consists essentially of peptidoglycane linked covalently with a lipoprotein and proteins of weak molecular weight. All attempts at more precise fractionation have until now led to the loss of biological activity."} {"id": "PMID:1261756", "title": "Quinidine hypersensitivity and liver involvement. A survey of 32 patients.", "content": "Thirty-two of 487 patients who received quinidine between the years of 1970 and 1974 in the departments of medicine at Hadassah University Hospital developed hypersensitivity reactions. Ten of the 32 patients had clinical and biochemical manifestations of liver invlovement. In 4 patients liver biopsy showed granulomatous hepatitis. It is therefore concluded that quinidine-induced hepatitis is a relatively common side effect of this drug.", "contents": "Quinidine hypersensitivity and liver involvement. A survey of 32 patients. Thirty-two of 487 patients who received quinidine between the years of 1970 and 1974 in the departments of medicine at Hadassah University Hospital developed hypersensitivity reactions. Ten of the 32 patients had clinical and biochemical manifestations of liver invlovement. In 4 patients liver biopsy showed granulomatous hepatitis. It is therefore concluded that quinidine-induced hepatitis is a relatively common side effect of this drug."} {"id": "PMID:1261757", "title": "Abnormalities of chemical tests for copper metabolism in chronic active liver disease: differentiation from Wilson's disease.", "content": "Because identical clinical findings, alterations of hepatic function, and changes in hepatic morphology can occur in Wilson's disease (WD) and chronic active liver disease (CALD), chemical tests that reflect copper metabolism are important in the differential diagnosis of these conditions. The authors therefore measured 24-hr urinary copper excretion, hepatic copper concentration, and serum ceruloplasmin concentration in 54 patients with CALD. Twenty-four hour urinary copper excretion was increased in about 50% of patients, was significantly higher during active disease compared to remission, and was in the WD range in approximately 10% of patients. Hepatic copper concentration was also increased in the majority of patients, generally during active disease, and it sometimes overlapped with values reported in WD. By contrast, serum ceruloplasmin levels were elevated in nearly one-half the Cald patients and were never below normal. It is concluded that the chemical tests routinely used to assess copper metabolism in WD are frequently abnormal in CALD. Because the serum ceruloplasmin concentration never fell in the WD range and often was elevated, it is the most reliable routine chemical screening test to differentiate between CALD and WD.", "contents": "Abnormalities of chemical tests for copper metabolism in chronic active liver disease: differentiation from Wilson's disease. Because identical clinical findings, alterations of hepatic function, and changes in hepatic morphology can occur in Wilson's disease (WD) and chronic active liver disease (CALD), chemical tests that reflect copper metabolism are important in the differential diagnosis of these conditions. The authors therefore measured 24-hr urinary copper excretion, hepatic copper concentration, and serum ceruloplasmin concentration in 54 patients with CALD. Twenty-four hour urinary copper excretion was increased in about 50% of patients, was significantly higher during active disease compared to remission, and was in the WD range in approximately 10% of patients. Hepatic copper concentration was also increased in the majority of patients, generally during active disease, and it sometimes overlapped with values reported in WD. By contrast, serum ceruloplasmin levels were elevated in nearly one-half the Cald patients and were never below normal. It is concluded that the chemical tests routinely used to assess copper metabolism in WD are frequently abnormal in CALD. Because the serum ceruloplasmin concentration never fell in the WD range and often was elevated, it is the most reliable routine chemical screening test to differentiate between CALD and WD."} {"id": "PMID:1261758", "title": "Esophageal motor dysfunction in idiopathic intestinal pseudoobstruction.", "content": "Five patients with idiopathic intestinal pseudoobstruction were studied with esophageal manometry and all had abnormalities of esophageal motility. In 2, primary peristalsis was replaced by simultaneous contractions and repetitive spontaneous activity was marked. The lower esophageal sphincter failed to relax and the Mecholyl test was positive in both. In the other 3, primary peristalsis was absent, low amplitude simultaneous waves followed swallows, no spontaneous activity was present, and defects in lower esophageal sphincter relaxation were found in two. The Mecholyl test was negative in the one patient tested. The esophagus appears to be abnormal in idiopathic intestinal pseudoobstruction and could prove useful as an organ for diagnostic study in patients who may have this syndrome.", "contents": "Esophageal motor dysfunction in idiopathic intestinal pseudoobstruction. Five patients with idiopathic intestinal pseudoobstruction were studied with esophageal manometry and all had abnormalities of esophageal motility. In 2, primary peristalsis was replaced by simultaneous contractions and repetitive spontaneous activity was marked. The lower esophageal sphincter failed to relax and the Mecholyl test was positive in both. In the other 3, primary peristalsis was absent, low amplitude simultaneous waves followed swallows, no spontaneous activity was present, and defects in lower esophageal sphincter relaxation were found in two. The Mecholyl test was negative in the one patient tested. The esophagus appears to be abnormal in idiopathic intestinal pseudoobstruction and could prove useful as an organ for diagnostic study in patients who may have this syndrome."} {"id": "PMID:1261759", "title": "Inhibition of gastric acid secretion in man by exogenous and endogenous pancreatic glucagon.", "content": "The interaction of intravenously infused glucagon and pentagastrin on gastric acid secretion was studied in 5 healthy subjects. First a step dose-response study with pentagastrin in doses of 0.01, 0.1,1.0, and 10.0 mug per kg-hr was performed. The dose required for one-half maximal response (D50) was 130 ng per kg-hr. With this dose of pentagastrin as background stimulation a step dose-response study with glucagon in doses of 0.5, 2.0, 8.0, and 16.0 mug per kg-hr was performed. The dose of glucagon required for one-half maximal inhibition was 1.64 mug per kg-hr. In a third experiment the dose-response study with pentagastrin was repeated on a background infusion of glucagon in the dose found to be D50. A significant inhibition of acid secretion was found on all dose levels. The inhibition followed noncompetitive kinetics. Plasma concentrations of pancreatic glucagon in 4 of the 5 subjects in this experiment were comparable concentrations seen after a protein meal. Intravenous infusion of l-arginine on a background stimulation of acid secretion with synthetic human gastrin I in a dose of 250 ng per kg-hr was performed in 7 healthy subjects. Arginine increased serum glucagon concentration to levels seen after a meal and resulted in a significant inhibition of acid secretion. The results favor the hypothesis that pancreatic glucagon may participate in the physiological inhibition of gastric acid secretion.", "contents": "Inhibition of gastric acid secretion in man by exogenous and endogenous pancreatic glucagon. The interaction of intravenously infused glucagon and pentagastrin on gastric acid secretion was studied in 5 healthy subjects. First a step dose-response study with pentagastrin in doses of 0.01, 0.1,1.0, and 10.0 mug per kg-hr was performed. The dose required for one-half maximal response (D50) was 130 ng per kg-hr. With this dose of pentagastrin as background stimulation a step dose-response study with glucagon in doses of 0.5, 2.0, 8.0, and 16.0 mug per kg-hr was performed. The dose of glucagon required for one-half maximal inhibition was 1.64 mug per kg-hr. In a third experiment the dose-response study with pentagastrin was repeated on a background infusion of glucagon in the dose found to be D50. A significant inhibition of acid secretion was found on all dose levels. The inhibition followed noncompetitive kinetics. Plasma concentrations of pancreatic glucagon in 4 of the 5 subjects in this experiment were comparable concentrations seen after a protein meal. Intravenous infusion of l-arginine on a background stimulation of acid secretion with synthetic human gastrin I in a dose of 250 ng per kg-hr was performed in 7 healthy subjects. Arginine increased serum glucagon concentration to levels seen after a meal and resulted in a significant inhibition of acid secretion. The results favor the hypothesis that pancreatic glucagon may participate in the physiological inhibition of gastric acid secretion."} {"id": "PMID:1261760", "title": "Pancreatic, gallbladder, and gastric responses to intraduodenal calcium perfusion in man.", "content": "To determine the effect of intraduodenal calcium on pancreatic, gallbladder, and gastric functions in healthy man, a validated perfusion method was employed to quantify total pancreatic, biliary, and gastric outputs during duodenal perfusion of either 6 mM, 12 mM,or 25 mM of elemental calcium (as isotonic calcium chloride solutions). Intraluminal calcium stimulated pancreatic enzyme secretion and gallbladder contraction in a dose-related fashion, achieving comparable responses to those produced by intravenous cholecystokinin-pancreozymin (CCK-z). Responses to calcium were reproducible when repeated in the same individual. Gastric acid outputs and serum gastrin levels increased significantly only with higher calcium perfusions (25 mM). Although duodenal calcium perfusion (25 mM) slightly increased serum calcium concentrations, induced hypercalcemia (by intravenous calcium infusion) of similar magnitude had no effect on pancreatic or gallbladder function. It is suggested that intraduodenal calcium may induce release of CCK-PZ (and/or other neurohormonal factors) from the gut, causing stimulation of these digestive organs.", "contents": "Pancreatic, gallbladder, and gastric responses to intraduodenal calcium perfusion in man. To determine the effect of intraduodenal calcium on pancreatic, gallbladder, and gastric functions in healthy man, a validated perfusion method was employed to quantify total pancreatic, biliary, and gastric outputs during duodenal perfusion of either 6 mM, 12 mM,or 25 mM of elemental calcium (as isotonic calcium chloride solutions). Intraluminal calcium stimulated pancreatic enzyme secretion and gallbladder contraction in a dose-related fashion, achieving comparable responses to those produced by intravenous cholecystokinin-pancreozymin (CCK-z). Responses to calcium were reproducible when repeated in the same individual. Gastric acid outputs and serum gastrin levels increased significantly only with higher calcium perfusions (25 mM). Although duodenal calcium perfusion (25 mM) slightly increased serum calcium concentrations, induced hypercalcemia (by intravenous calcium infusion) of similar magnitude had no effect on pancreatic or gallbladder function. It is suggested that intraduodenal calcium may induce release of CCK-PZ (and/or other neurohormonal factors) from the gut, causing stimulation of these digestive organs."} {"id": "PMID:1261761", "title": "Free intrinsic factor in the small intestine in man.", "content": "Human jejunal and ileal contents and ileostomy effluents were examined for the presence of free intrinsic factor. This was detected in 9 out of 10 jejunal and three out of five ileal aspirates and in one of three ileostomy effluents studied. The intrinsic factor in the ileal effluent was shown to be physiologically active. The presence of free intrinsic factor in the small intestine has considerable physiological significance in maintaining the enterophepatic circulation of vitamin B12. It would also permit the absorption of any free vitamin B12 produced by ileal bacteria.", "contents": "Free intrinsic factor in the small intestine in man. Human jejunal and ileal contents and ileostomy effluents were examined for the presence of free intrinsic factor. This was detected in 9 out of 10 jejunal and three out of five ileal aspirates and in one of three ileostomy effluents studied. The intrinsic factor in the ileal effluent was shown to be physiologically active. The presence of free intrinsic factor in the small intestine has considerable physiological significance in maintaining the enterophepatic circulation of vitamin B12. It would also permit the absorption of any free vitamin B12 produced by ileal bacteria."} {"id": "PMID:1261762", "title": "Ileal crypt cell population kinetics after 40% small bowel resection. Autoradiographic studies in the rat.", "content": "Ileal crypt cell population kinetics were investigated by autoradiography with tritiated thymidine in rats 60 days after resection of a jejunal segment equivalent to 40% of the length of the small bowel. Controls were subjected to transection and anastomosis. The mean total number of cells and the mean number of labeled cells per crypt cell column were estimated. The distribution of proliferating cells was obtained by determining the percentage of labeled cells at each cell position in the crypt cell columns. The cell cycle was analyzed by the method of percentage-labeled metaphases. The mean total number of cells was increased from 30.5 to 36.6 (P less than 0.002) and the mean number of labeled cells per crypt cell column was increased from 10.2 to 12.4 (P less than 0.001). Labeling index was unaltered. The mean sizes of the proliferative and maturation zones were increased (P less than 0.002). The estimated median duration of the cell cycle was 11.5 hr in the control group and 10.5 hr in the resection group. The duration of DNA synthesis was 6.4 hr in both groups. It is concluded that 40% small bowel resection increases cell renewal by expanding the size of the proliferative zone of the crypt cell population.", "contents": "Ileal crypt cell population kinetics after 40% small bowel resection. Autoradiographic studies in the rat. Ileal crypt cell population kinetics were investigated by autoradiography with tritiated thymidine in rats 60 days after resection of a jejunal segment equivalent to 40% of the length of the small bowel. Controls were subjected to transection and anastomosis. The mean total number of cells and the mean number of labeled cells per crypt cell column were estimated. The distribution of proliferating cells was obtained by determining the percentage of labeled cells at each cell position in the crypt cell columns. The cell cycle was analyzed by the method of percentage-labeled metaphases. The mean total number of cells was increased from 30.5 to 36.6 (P less than 0.002) and the mean number of labeled cells per crypt cell column was increased from 10.2 to 12.4 (P less than 0.001). Labeling index was unaltered. The mean sizes of the proliferative and maturation zones were increased (P less than 0.002). The estimated median duration of the cell cycle was 11.5 hr in the control group and 10.5 hr in the resection group. The duration of DNA synthesis was 6.4 hr in both groups. It is concluded that 40% small bowel resection increases cell renewal by expanding the size of the proliferative zone of the crypt cell population."} {"id": "PMID:1261763", "title": "Acute hemorrhagic pancreatic necrosis in mice. Intraparenchymal activation of zymogens, and other enzyme changes in pancreas and serum.", "content": "A new experimental model has been found whereby acute hemorrhagic pancreatic necrosis with fat necrosis is induced in 100% of young female mice fed a choline-deficient diet supplemented with 0.5% DL-ethioine. The onset of the pancreatic necrosis has been shown to follow accumulation, and subsequent activation, of pancreatic zymogens with intraparenchymal formation of significant amounts of elastase, chymotrypsin, and trypsin. Evidence was obtained that the proteolytic enzymes are released also in the circulation and cause a significant drop in the content of the serum protease inhibition alpha 1-antitrypsin and alpha2-macroglobulin. Increased levels of plasma amylase were found to accompany the onset of the pancreatic necrosis.", "contents": "Acute hemorrhagic pancreatic necrosis in mice. Intraparenchymal activation of zymogens, and other enzyme changes in pancreas and serum. A new experimental model has been found whereby acute hemorrhagic pancreatic necrosis with fat necrosis is induced in 100% of young female mice fed a choline-deficient diet supplemented with 0.5% DL-ethioine. The onset of the pancreatic necrosis has been shown to follow accumulation, and subsequent activation, of pancreatic zymogens with intraparenchymal formation of significant amounts of elastase, chymotrypsin, and trypsin. Evidence was obtained that the proteolytic enzymes are released also in the circulation and cause a significant drop in the content of the serum protease inhibition alpha 1-antitrypsin and alpha2-macroglobulin. Increased levels of plasma amylase were found to accompany the onset of the pancreatic necrosis."} {"id": "PMID:1261764", "title": "Effect of hypophysectomy and growth hormone on serum and antral gastrin levels in the rat.", "content": "The effects of hypophysectomy and subsequent replacement therapy with growth hormone on serum and antral gastrin levels was investigated in both fasted and nonfasted pair-fed rats. Hypophysectomy caused a 57% decrease in serum and 47% decrease in antral gastrin content in 18-hr fasted animals. In nonfasted animals, hypophysectomy resulted in a 42% fall in serum gastrin and a 76% fall in antral gastrin. Animals were given injections of growth hormone over a 10-day period, then fasted 16 to 18 hr before being killed. Doses of 100 to 200 mug per 100 g of body weight were ineffective, but a dose of 500 mug per 100 g was sufficient to restore completely serum gastrin levels to intact control values. In nofasted rats this same dose raised serum gastrin to intact levels and increased antral gastrin significantly over hypophysectomized levels, but did not increase it to control values. When given to pair-fed intact animals, growth hormone caused slight but not significant elevations in serum and antral gastrin. The effect of growth hormone on gastrin secretion and /or synthesis may be a significant physiological factor in the regulation of normal gastrointestinal function and growth.", "contents": "Effect of hypophysectomy and growth hormone on serum and antral gastrin levels in the rat. The effects of hypophysectomy and subsequent replacement therapy with growth hormone on serum and antral gastrin levels was investigated in both fasted and nonfasted pair-fed rats. Hypophysectomy caused a 57% decrease in serum and 47% decrease in antral gastrin content in 18-hr fasted animals. In nonfasted animals, hypophysectomy resulted in a 42% fall in serum gastrin and a 76% fall in antral gastrin. Animals were given injections of growth hormone over a 10-day period, then fasted 16 to 18 hr before being killed. Doses of 100 to 200 mug per 100 g of body weight were ineffective, but a dose of 500 mug per 100 g was sufficient to restore completely serum gastrin levels to intact control values. In nofasted rats this same dose raised serum gastrin to intact levels and increased antral gastrin significantly over hypophysectomized levels, but did not increase it to control values. When given to pair-fed intact animals, growth hormone caused slight but not significant elevations in serum and antral gastrin. The effect of growth hormone on gastrin secretion and /or synthesis may be a significant physiological factor in the regulation of normal gastrointestinal function and growth."} {"id": "PMID:1261765", "title": "Stimulation of gastric acid secretion in the dog by the C-terminal penta-, tetra-, and tripeptides of gastrin and their O-methyl esters.", "content": "Acid secretion from the vagally innervated gastric fistula of conscious dogs was stimulated in a dose-related manner by the C-terminal penta-, tetra-, and tripetide amides of gastrin, the o-methyl esters of the tetra- and tripeptides, and the sulfone derivative of the tetrapeptide amide. The potency and efficacy of Peptavalon and the C-terminal penta- and tetrapeptide amides were about the same on a weight or molar basis. On a molar basis, the pentapeptide amide was about 4300 times as potent as the tripeptide amide. The o-methyl ester and the sulfone derivative of the tetrapeptide were about equipotent; they were, respectively, one-twenty-fifth and one-thirtieth as potent as the tetrapeptide amide. The dipetide amides did not stimulate acid secretion in a dose range of 50 to 1500 mug per kg-hr. The results indicate that (1) the C-terminal tetrapeptide amide cannot be the minimal effective \"stump\" for biological activity in the gastrin molecule, (2) the C-terminal amide is important but not essential for gastric stimulating power, and (3) oxidation of the sulfur atom of the methionyl residue in the tetrapeptide does not result in total loss of activity.", "contents": "Stimulation of gastric acid secretion in the dog by the C-terminal penta-, tetra-, and tripeptides of gastrin and their O-methyl esters. Acid secretion from the vagally innervated gastric fistula of conscious dogs was stimulated in a dose-related manner by the C-terminal penta-, tetra-, and tripetide amides of gastrin, the o-methyl esters of the tetra- and tripeptides, and the sulfone derivative of the tetrapeptide amide. The potency and efficacy of Peptavalon and the C-terminal penta- and tetrapeptide amides were about the same on a weight or molar basis. On a molar basis, the pentapeptide amide was about 4300 times as potent as the tripeptide amide. The o-methyl ester and the sulfone derivative of the tetrapeptide were about equipotent; they were, respectively, one-twenty-fifth and one-thirtieth as potent as the tetrapeptide amide. The dipetide amides did not stimulate acid secretion in a dose range of 50 to 1500 mug per kg-hr. The results indicate that (1) the C-terminal tetrapeptide amide cannot be the minimal effective \"stump\" for biological activity in the gastrin molecule, (2) the C-terminal amide is important but not essential for gastric stimulating power, and (3) oxidation of the sulfur atom of the methionyl residue in the tetrapeptide does not result in total loss of activity."} {"id": "PMID:1261766", "title": "Effect of growth hormone release-inhibiting hormone on gastric secretion, mucosal blood flow, and serum gastrin.", "content": "In dogs with gastric fistulae and Heidenhain pouches (HP) growth hormone release-inhibiting hormone (GH-RIH) infused intravenously in a dose of 2.5 mug per kg per hr inhibited almost completely acid and pepsin responses to pentagastrin, Urecholine, and a peptone. Histamine-induced acid secretion was more resistant to the inhibition by GH-RIH, and only acid secretion evoked by the lower doses of histamine was suppressed by this peptide. The inhibition of pentagastrin-induced gastric secretion was associated with a marked reduction in mucosal blood flow. The ratio of aminopyrine concentration in the gastric juice and blood plasma was not significantly changed by GH-RIH, indicating that the reduction in mucosal blood flow was secondary to an inhibition of gastric secretion. Gastric acid and serum gastrin responses to a peptone meal adjusted to pH 5.0 and kept in the main stomach at this same pH by intragastric titration were significantly decreased by GH-RIH, indicating that the observed acid inhibition could be attributed at least in part to the suppression of gastrin release. GH-RIH inhibited acid secretion from HP stimulated by liver extract in HP. The finding that GH-RIH inhibits gastric secretion induced by exogenous stimulants as well as by the direct chemical stimulation of the HP mucosa without changing serum gastrin level suggests that the major action of GH-RIH is a direct suppression of the oxyntic glands.", "contents": "Effect of growth hormone release-inhibiting hormone on gastric secretion, mucosal blood flow, and serum gastrin. In dogs with gastric fistulae and Heidenhain pouches (HP) growth hormone release-inhibiting hormone (GH-RIH) infused intravenously in a dose of 2.5 mug per kg per hr inhibited almost completely acid and pepsin responses to pentagastrin, Urecholine, and a peptone. Histamine-induced acid secretion was more resistant to the inhibition by GH-RIH, and only acid secretion evoked by the lower doses of histamine was suppressed by this peptide. The inhibition of pentagastrin-induced gastric secretion was associated with a marked reduction in mucosal blood flow. The ratio of aminopyrine concentration in the gastric juice and blood plasma was not significantly changed by GH-RIH, indicating that the reduction in mucosal blood flow was secondary to an inhibition of gastric secretion. Gastric acid and serum gastrin responses to a peptone meal adjusted to pH 5.0 and kept in the main stomach at this same pH by intragastric titration were significantly decreased by GH-RIH, indicating that the observed acid inhibition could be attributed at least in part to the suppression of gastrin release. GH-RIH inhibited acid secretion from HP stimulated by liver extract in HP. The finding that GH-RIH inhibits gastric secretion induced by exogenous stimulants as well as by the direct chemical stimulation of the HP mucosa without changing serum gastrin level suggests that the major action of GH-RIH is a direct suppression of the oxyntic glands."} {"id": "PMID:1261767", "title": "Cholinergic release of gastrin by feeding in cats.", "content": "The effect of atropine on acid secretion and serum gastrin level after feeding was studied in 8 cats with denervated fundic pouches (Heidenhain pouch, HP). Serum gastrin concentration was measured by radioimmunoassay. In the control experiments, the mean peak acid response occurred 45 min after feeding and the mean peak gastrin concentration 15 min after feeding. After the 1st postprandial hr, acid secretion declined but the gastrin level remained elevated. Atropine, 0.1 mg per kg intravenously 5 min before feeding, depressed both acid secretion and the increase in serum gastrin concentration during the 1st postprandial hr. In both the control and atropine experiments, acid secretion and serum gastrin level were correlated significantly during the 1st postprandial hr, but no correlation was found later in the experiments. The reduction by atropine of the acid and serum gastrin responses varied among the cats but were correlated significantly. It is concluded that a cholinergic mechanism is implicated in the release of gastrin by feeding in cats during the 1st postprandial hr. Atropine reduces the HP acid response to feeding at least in part by depressing the release of gastrin.", "contents": "Cholinergic release of gastrin by feeding in cats. The effect of atropine on acid secretion and serum gastrin level after feeding was studied in 8 cats with denervated fundic pouches (Heidenhain pouch, HP). Serum gastrin concentration was measured by radioimmunoassay. In the control experiments, the mean peak acid response occurred 45 min after feeding and the mean peak gastrin concentration 15 min after feeding. After the 1st postprandial hr, acid secretion declined but the gastrin level remained elevated. Atropine, 0.1 mg per kg intravenously 5 min before feeding, depressed both acid secretion and the increase in serum gastrin concentration during the 1st postprandial hr. In both the control and atropine experiments, acid secretion and serum gastrin level were correlated significantly during the 1st postprandial hr, but no correlation was found later in the experiments. The reduction by atropine of the acid and serum gastrin responses varied among the cats but were correlated significantly. It is concluded that a cholinergic mechanism is implicated in the release of gastrin by feeding in cats during the 1st postprandial hr. Atropine reduces the HP acid response to feeding at least in part by depressing the release of gastrin."} {"id": "PMID:1261768", "title": "Prevention of secretagogue-induced ulcers in the rat.", "content": "An inhibitor of gastric secretion, Pfizer UK -9040, a derivative of the antihistamine triprolidine, was given orally 50 to 100 mg per kg 1 hr before and at various times during a 24-hr subcutanwous infusion of ulcerogenic secretagogues. The higher the dose and the more frequent the dosage, the lower was the incidence, severity, number, and perforations of duodenal ulcers. The mechanisms by which UK -9040 prevents these ulcers is probably inhibition of gastric secretion.", "contents": "Prevention of secretagogue-induced ulcers in the rat. An inhibitor of gastric secretion, Pfizer UK -9040, a derivative of the antihistamine triprolidine, was given orally 50 to 100 mg per kg 1 hr before and at various times during a 24-hr subcutanwous infusion of ulcerogenic secretagogues. The higher the dose and the more frequent the dosage, the lower was the incidence, severity, number, and perforations of duodenal ulcers. The mechanisms by which UK -9040 prevents these ulcers is probably inhibition of gastric secretion."} {"id": "PMID:1261769", "title": "Intestinal propulsion in the dog. Its relation to food intake and the migratory myoelectric complex.", "content": "We studied electrical events and flow in the canine small intestine in vivo. The transit of a small radioactive bolus injected into the jejunum was monitored by counting from a Biebl loop. After feeding, the rate of propulsion of the bolus varied within a narrow range. When food and water were withheld for more than 12 hr, transit of the bolus hecame highly variable. The variability increased at about the same time as the onset of the migratory myoelectric complex associated with fasting. Electrical recordings from the intestinal muscle demonstrated that the bolus was propelled into the loop in advance of the band of intense spike potentials which travels along the small intestine in the fasted state. The bolus was cleared from the loop when the spike potentials reached this segment. Variability of transit after prolonged fasting can be explained by (1) variability in the rate of migration of the phase of intense spike potentials, and (2) the timing of the injection of the bolus in relation to the component phases of the electrical complex. Flow is highly dependent upon the electrical activity and the resulting contraction patterns of the small intestine, which are themselves dependent upon feeding.", "contents": "Intestinal propulsion in the dog. Its relation to food intake and the migratory myoelectric complex. We studied electrical events and flow in the canine small intestine in vivo. The transit of a small radioactive bolus injected into the jejunum was monitored by counting from a Biebl loop. After feeding, the rate of propulsion of the bolus varied within a narrow range. When food and water were withheld for more than 12 hr, transit of the bolus hecame highly variable. The variability increased at about the same time as the onset of the migratory myoelectric complex associated with fasting. Electrical recordings from the intestinal muscle demonstrated that the bolus was propelled into the loop in advance of the band of intense spike potentials which travels along the small intestine in the fasted state. The bolus was cleared from the loop when the spike potentials reached this segment. Variability of transit after prolonged fasting can be explained by (1) variability in the rate of migration of the phase of intense spike potentials, and (2) the timing of the injection of the bolus in relation to the component phases of the electrical complex. Flow is highly dependent upon the electrical activity and the resulting contraction patterns of the small intestine, which are themselves dependent upon feeding."} {"id": "PMID:1261770", "title": "Inflammatory bowel disease in all three members of one family.", "content": "The occurrence of inflammatory bowel disease in all three members of one family is described. Studies of white blood cell chromosomes, histocompatibility antigens, and cellular and humoral immunity failed to explain this unusual phenomenon. However, the appearance of inflammatory bowel disease in an entire family reemphasizes the potential role of genetic and environmental influences in the pathogenesis of some cases of ulcerative colitis and Crohn's disease.", "contents": "Inflammatory bowel disease in all three members of one family. The occurrence of inflammatory bowel disease in all three members of one family is described. Studies of white blood cell chromosomes, histocompatibility antigens, and cellular and humoral immunity failed to explain this unusual phenomenon. However, the appearance of inflammatory bowel disease in an entire family reemphasizes the potential role of genetic and environmental influences in the pathogenesis of some cases of ulcerative colitis and Crohn's disease."} {"id": "PMID:1261771", "title": "Bilirubin secretion and conjujation in the Crigler-Najjar syndrome type II.", "content": "Features characteristic of the Crigler-Najjar syndrome (type II) are described in an adolescent boy with severe congenital unconjugated hyperbilirubinemia. Bilirubin encephalopathy developed only in early puberty after surgery and fasting, coincident with a dramatic rise in serum bilirubin, which responded to intensive therapy. Fasting was later shown to increase markedly the serum bilirubin levels and probably was a major factor in precipitating the initial acute event. One year later, while the patient was in a metabolic steady state, the secretion rate of bilirubin was measured by aduodenal marker-perfusion technique, and the nature of the secreted bilirubin conjugates was characterized. Total bilirubin secretion rates were low, 4.39 mg per hr and 4.44 mg per hr on two separate studies. The major pigment detected in bile was bilirubin monoglucuronide. Bilirubin diglucuronide comprised only a minor fraction of the pigments, and other conjugates were not detected. The present study documents a reduced biliary bilirubin secretion and suggests that the addition of the second glucuronic acid moiety to the bilirubin molecule may be defective in Crigler-Najjar syndrome (type II).", "contents": "Bilirubin secretion and conjujation in the Crigler-Najjar syndrome type II. Features characteristic of the Crigler-Najjar syndrome (type II) are described in an adolescent boy with severe congenital unconjugated hyperbilirubinemia. Bilirubin encephalopathy developed only in early puberty after surgery and fasting, coincident with a dramatic rise in serum bilirubin, which responded to intensive therapy. Fasting was later shown to increase markedly the serum bilirubin levels and probably was a major factor in precipitating the initial acute event. One year later, while the patient was in a metabolic steady state, the secretion rate of bilirubin was measured by aduodenal marker-perfusion technique, and the nature of the secreted bilirubin conjugates was characterized. Total bilirubin secretion rates were low, 4.39 mg per hr and 4.44 mg per hr on two separate studies. The major pigment detected in bile was bilirubin monoglucuronide. Bilirubin diglucuronide comprised only a minor fraction of the pigments, and other conjugates were not detected. The present study documents a reduced biliary bilirubin secretion and suggests that the addition of the second glucuronic acid moiety to the bilirubin molecule may be defective in Crigler-Najjar syndrome (type II)."} {"id": "PMID:1261772", "title": "Fulminant hepatitis and lymphocyte sensitization due to propylthiouracil.", "content": "Fulminant hepatic failure developed in a 24-year-old black woman who had been treated with propylthiouracil and propranolol for hyperthyroidism. Clinical and biochemical recovery followed discontinuation of drug therapy. Liver biopsy disclosed submassive hepatic necrosis. During the acute phase of the disease, lymphocyte transformation studies revealed sensitization of the patient's lymphocytes to propylthiouracil but not to propranolol. Sensitization remained demonstrable 2 months after cessation of the former drug. Lymphocytes obtained from a hyperthyroid patient treated with propylthiouracil without complications failed to show evidence of sensitization. These observations indicate that submassive hepatic necrosis may result from treatment with propylthiouracil and are consistent with the notion that sensitization mechanisms may be responsible for the hepatic injury induced by this drug.", "contents": "Fulminant hepatitis and lymphocyte sensitization due to propylthiouracil. Fulminant hepatic failure developed in a 24-year-old black woman who had been treated with propylthiouracil and propranolol for hyperthyroidism. Clinical and biochemical recovery followed discontinuation of drug therapy. Liver biopsy disclosed submassive hepatic necrosis. During the acute phase of the disease, lymphocyte transformation studies revealed sensitization of the patient's lymphocytes to propylthiouracil but not to propranolol. Sensitization remained demonstrable 2 months after cessation of the former drug. Lymphocytes obtained from a hyperthyroid patient treated with propylthiouracil without complications failed to show evidence of sensitization. These observations indicate that submassive hepatic necrosis may result from treatment with propylthiouracil and are consistent with the notion that sensitization mechanisms may be responsible for the hepatic injury induced by this drug."} {"id": "PMID:1261773", "title": "Adenocarcinoma in biliary papillomatosis.", "content": "A patient with multicentric biliary papillomatosis associated with invasive adenocarcinoma of the bile duct is reported. This case documents the progression to malignancy of a lesion generally thought to be benign. It serves to alert clinicians to a rare but important cause of recurrent biliary obstruction. The literature on this entity is reviewed.", "contents": "Adenocarcinoma in biliary papillomatosis. A patient with multicentric biliary papillomatosis associated with invasive adenocarcinoma of the bile duct is reported. This case documents the progression to malignancy of a lesion generally thought to be benign. It serves to alert clinicians to a rare but important cause of recurrent biliary obstruction. The literature on this entity is reviewed."} {"id": "PMID:1261781", "title": "The mechanism of action of gastrin on the lower esophageal sphincter.", "content": "Gastrin I or pentagastrin caused contraction of the lowe esophageal sphincter in anesthetized oppossums. The contraction was not modified, either qualitatively or quantitatively, by 30 or 1000 mug per kg atropine pretreatment. Moreover, neural block with tetrodotoxin did not influence the effect of gastrin on the sphincter pressure. H2 receptor antagonist, metiamide, did not modify the magnitude of the contractile response of the lower esophageal sphincter to gastrin I. These studies show: a) gastrin does not cause sphincter contraction by stimulating cholinergic neurons: and b) gastrin does not exert an inhibitory effect on the sponcter pressure by stimulating H2 receptors. We suggest that gastrin may contract the lower esophageal sphincter by a direct action on the sphincter muscle.", "contents": "The mechanism of action of gastrin on the lower esophageal sphincter. Gastrin I or pentagastrin caused contraction of the lowe esophageal sphincter in anesthetized oppossums. The contraction was not modified, either qualitatively or quantitatively, by 30 or 1000 mug per kg atropine pretreatment. Moreover, neural block with tetrodotoxin did not influence the effect of gastrin on the sphincter pressure. H2 receptor antagonist, metiamide, did not modify the magnitude of the contractile response of the lower esophageal sphincter to gastrin I. These studies show: a) gastrin does not cause sphincter contraction by stimulating cholinergic neurons: and b) gastrin does not exert an inhibitory effect on the sponcter pressure by stimulating H2 receptors. We suggest that gastrin may contract the lower esophageal sphincter by a direct action on the sphincter muscle."} {"id": "PMID:1261783", "title": "[Operative procedures for male sterilization (author's transl)].", "content": "The sterilization of the male by vasectomy receives increasing acceptance in this country as part of family planning in general. Current laws and bylaws are lacking. The present procedures, indications and methods for vasectomy for fertility are described and discussed. This type of vasectomy differs in some points from vasectomy for other therapeutic indications. Noticeable complications, especially immunologic complications were not observed and were not detectable by immunologic testing of 23 men. Since all attempts to achieve a temporary occlusion of the vas have failed, vasectomy for the control of fertility is irreversible, in the majority of the cases. It is therefore advisable to deposit semen in sperm banks in these cases. The success rate of re-anastomosis of the vas to the vas or the vas to the epididimus varies between 10 and 30%.", "contents": "[Operative procedures for male sterilization (author's transl)]. The sterilization of the male by vasectomy receives increasing acceptance in this country as part of family planning in general. Current laws and bylaws are lacking. The present procedures, indications and methods for vasectomy for fertility are described and discussed. This type of vasectomy differs in some points from vasectomy for other therapeutic indications. Noticeable complications, especially immunologic complications were not observed and were not detectable by immunologic testing of 23 men. Since all attempts to achieve a temporary occlusion of the vas have failed, vasectomy for the control of fertility is irreversible, in the majority of the cases. It is therefore advisable to deposit semen in sperm banks in these cases. The success rate of re-anastomosis of the vas to the vas or the vas to the epididimus varies between 10 and 30%."} {"id": "PMID:1261787", "title": "[Does oral contraception cause cancer? (author's transl)].", "content": "A complete answer to the question of the relationship between malignant tumors in man and the administration of contraceptive steroids is at present not possible. Difficulties of the investigation are caused by the multiplicity of compounds used for contraception, the generally slow development of malignant tumors and the difficulty of the epidemiologic and statistical investigations on the multi-factorial etiology of cancer. Nevertheless, it can be stated with a high degree of certainty that \"cancer due to the pill\" does not exist in man and that a direct hormonal induction of malignant tumors in man cannot be proved. The question whether oral contraceptives may favor the development of cancer indirectly is explored in this paper regarding cancer of the female genital tract and the breast. No correlation between oral contraception and squamous cell carcinomas of the vulva and vagina and tumors of the ovary is known. As yet no statistics are available on the incidence of carcinoma of the endometrium in women who took oral contraceptives during their reproductive life span. Because of the direct hormonal suppression of the endometrial growth by oral contraception, a protective effect against endometrial hyperplasia and endometrial cancer must be expected. For cancer of the female breast no protective and no enhancing cancer risk due to progestational agents can be postulated. The known fragmentary data suggest a more protective value. Regarding dysplasia and carcinoma in situ of the uterine cervix large investigations in high numbers of patients are available. An increase of the risk to develop cancer of the cervix by using oral contraception cannot be shown with sufficient accuracy at our present state of knowledge by statistical means. Some observations suggest that oral contraception increases the relevant exogenous factors for carcinogenesis of the uterine cervix such as sexual behavior and hygiene.", "contents": "[Does oral contraception cause cancer? (author's transl)]. A complete answer to the question of the relationship between malignant tumors in man and the administration of contraceptive steroids is at present not possible. Difficulties of the investigation are caused by the multiplicity of compounds used for contraception, the generally slow development of malignant tumors and the difficulty of the epidemiologic and statistical investigations on the multi-factorial etiology of cancer. Nevertheless, it can be stated with a high degree of certainty that \"cancer due to the pill\" does not exist in man and that a direct hormonal induction of malignant tumors in man cannot be proved. The question whether oral contraceptives may favor the development of cancer indirectly is explored in this paper regarding cancer of the female genital tract and the breast. No correlation between oral contraception and squamous cell carcinomas of the vulva and vagina and tumors of the ovary is known. As yet no statistics are available on the incidence of carcinoma of the endometrium in women who took oral contraceptives during their reproductive life span. Because of the direct hormonal suppression of the endometrial growth by oral contraception, a protective effect against endometrial hyperplasia and endometrial cancer must be expected. For cancer of the female breast no protective and no enhancing cancer risk due to progestational agents can be postulated. The known fragmentary data suggest a more protective value. Regarding dysplasia and carcinoma in situ of the uterine cervix large investigations in high numbers of patients are available. An increase of the risk to develop cancer of the cervix by using oral contraception cannot be shown with sufficient accuracy at our present state of knowledge by statistical means. Some observations suggest that oral contraception increases the relevant exogenous factors for carcinogenesis of the uterine cervix such as sexual behavior and hygiene."} {"id": "PMID:1261788", "title": "[Advantages and disadvantages of deliveries after induction of labour by convenience (author's transl)].", "content": "The development of 601 deliveries after induction of labour by convenience, 92 births after induced labour following pregnancies at risk and 1829 births after spontaneous onset of labour were examined and compared. The data were recorded retrospectively and submitted to an electronic data processing. Patients with whom the labour was induced had the shortest birth times, the difference amounted on average to 2 hours. In the comparison collective with spontaneous setting in of labour a hypotonic uterus motility was found to be the most frequent pathological labour activity. Pathological pattern of heart frequency, especially late decelerations were most frequently registered with fetuses of the risk group. The frequency of the operative deliveries amounted to 13% in the case of the collective of the induced labour, 35,9% in the case of patients in the risk group, and 10% in the case of the comparison collective. Threatening fetal asphyxia and protracted extrusion period were in the case of primiparas after induced labour equally often the indication for a vaginal-operative delivery, whereas with the comparison collective, in the risk group and also with multiparas after induced labour, the threatening fetal asphyxia was primarily for the carrying out of a forceps delivery or a vacuum extraction. Concerning the birth weight and size the new-borns of the collectives examined showed no significant differences. The best Apgar-score was achieved by the new-born induced labour babies. Only 0,5% of these babies showed pronounced signs of placental dysfunction, in the risk group 9,6%, and in the comparison collective 1,6% of the babies were born with a pronounced Clifford-syndrome. Induced labour babies did not need any pediatric treatment. There were no perinatal deaths. In the case of comparison collective, long term pediatric treatment was necessary for 8 babies, 1 baby died subpartual, another one in the pediatric clinic, that means a perinatal mortality of 0,1%. In the risk group 3 babies needed pediatric treatment, 1 baby died of the consequences of a serious erythroblastosis, the perinatal mortality amounted to 1,1%. In a critical evaluation of the without exception favourable obstetrical results after induced labour, the technical, personal and organisational efforts should not be overlooked. This stands in the way of a widespread use of the process in the near future. The results hitherto permit the temporary inference that 1) psychologically positive prerequisites for the birth are created if the pregnant woman knows a firm date for the delivery, 2) the whole partus can be continuously supervised and the maternal and infantile emergencies prevented in good time and 3) through the calculability of risks during pregnancy and birth, perinatal mortality and morbidity can be reduced considerably.", "contents": "[Advantages and disadvantages of deliveries after induction of labour by convenience (author's transl)]. The development of 601 deliveries after induction of labour by convenience, 92 births after induced labour following pregnancies at risk and 1829 births after spontaneous onset of labour were examined and compared. The data were recorded retrospectively and submitted to an electronic data processing. Patients with whom the labour was induced had the shortest birth times, the difference amounted on average to 2 hours. In the comparison collective with spontaneous setting in of labour a hypotonic uterus motility was found to be the most frequent pathological labour activity. Pathological pattern of heart frequency, especially late decelerations were most frequently registered with fetuses of the risk group. The frequency of the operative deliveries amounted to 13% in the case of the collective of the induced labour, 35,9% in the case of patients in the risk group, and 10% in the case of the comparison collective. Threatening fetal asphyxia and protracted extrusion period were in the case of primiparas after induced labour equally often the indication for a vaginal-operative delivery, whereas with the comparison collective, in the risk group and also with multiparas after induced labour, the threatening fetal asphyxia was primarily for the carrying out of a forceps delivery or a vacuum extraction. Concerning the birth weight and size the new-borns of the collectives examined showed no significant differences. The best Apgar-score was achieved by the new-born induced labour babies. Only 0,5% of these babies showed pronounced signs of placental dysfunction, in the risk group 9,6%, and in the comparison collective 1,6% of the babies were born with a pronounced Clifford-syndrome. Induced labour babies did not need any pediatric treatment. There were no perinatal deaths. In the case of comparison collective, long term pediatric treatment was necessary for 8 babies, 1 baby died subpartual, another one in the pediatric clinic, that means a perinatal mortality of 0,1%. In the risk group 3 babies needed pediatric treatment, 1 baby died of the consequences of a serious erythroblastosis, the perinatal mortality amounted to 1,1%. In a critical evaluation of the without exception favourable obstetrical results after induced labour, the technical, personal and organisational efforts should not be overlooked. This stands in the way of a widespread use of the process in the near future. The results hitherto permit the temporary inference that 1) psychologically positive prerequisites for the birth are created if the pregnant woman knows a firm date for the delivery, 2) the whole partus can be continuously supervised and the maternal and infantile emergencies prevented in good time and 3) through the calculability of risks during pregnancy and birth, perinatal mortality and morbidity can be reduced considerably."} {"id": "PMID:1261789", "title": "[Progress and change in geriatric gynecological surgery (author's transl)].", "content": "Two periods of geriatric gynecological surgery (1947-1959 and 1960-1972) at the University Women's Hospital in Hamburg-Eppendorf were compared in regard to the age of the patient, surgical indications, surgical procedure, anesthetic technique, preoperative and postoperative morbidity, length of hospitalization and mortality rate. During a period of 26 years, 1514 women over the age of 60 were treated surgically. During the first period, 489 women were treated, and in the second period, 1,025. This 109.6% increase has been confirmed statistically. The increase in geriatric surgical cases stems basically from the increase in the number of surgical patients over the age of 70. The increase in breast carcinoma during the second period (from 43 to 348 operations) is most conspicuous. This is an increase of 809.3%. On the basis of this disproportionately large increase in breast surgery, more women were treated surgically in the University Women's Hospital in Hamburg-Eppendorf for breast carcinoma during the second period, than for carcinoma of the reproductive organs. Vulva carcinoma and craurosis vulvae were also more frequently considered to be an indication for surgical treatment. The total number of women who were surgically treated for prolapsed uterus and vagina remained more or less constant. In the analyzing the surgical records, it should be emphasized that, in the second observation period, two-thirds of these cases were treated by performing a vaginal hysterectomy with anterior and posterior vaginoplasty. For older patients, palliative surgical measures for prolapsed uterus and vagina were abandoned in favor of more definitive methods. The postoperative morbidity and mortality rate remained more or less constant for both periods. The postoperative period of hospitalization was slightly longer while the preoperative period was slightly shorter. The statistically confirmed increase in geriatric surgery during the last 13 years at the University Women's Hospital in Hamburg-Eppendorf clearly shows how important geriatric surgery has become. The immediate consequences are an increased workload for physicians, nursing staff and physical therapists.", "contents": "[Progress and change in geriatric gynecological surgery (author's transl)]. Two periods of geriatric gynecological surgery (1947-1959 and 1960-1972) at the University Women's Hospital in Hamburg-Eppendorf were compared in regard to the age of the patient, surgical indications, surgical procedure, anesthetic technique, preoperative and postoperative morbidity, length of hospitalization and mortality rate. During a period of 26 years, 1514 women over the age of 60 were treated surgically. During the first period, 489 women were treated, and in the second period, 1,025. This 109.6% increase has been confirmed statistically. The increase in geriatric surgical cases stems basically from the increase in the number of surgical patients over the age of 70. The increase in breast carcinoma during the second period (from 43 to 348 operations) is most conspicuous. This is an increase of 809.3%. On the basis of this disproportionately large increase in breast surgery, more women were treated surgically in the University Women's Hospital in Hamburg-Eppendorf for breast carcinoma during the second period, than for carcinoma of the reproductive organs. Vulva carcinoma and craurosis vulvae were also more frequently considered to be an indication for surgical treatment. The total number of women who were surgically treated for prolapsed uterus and vagina remained more or less constant. In the analyzing the surgical records, it should be emphasized that, in the second observation period, two-thirds of these cases were treated by performing a vaginal hysterectomy with anterior and posterior vaginoplasty. For older patients, palliative surgical measures for prolapsed uterus and vagina were abandoned in favor of more definitive methods. The postoperative morbidity and mortality rate remained more or less constant for both periods. The postoperative period of hospitalization was slightly longer while the preoperative period was slightly shorter. The statistically confirmed increase in geriatric surgery during the last 13 years at the University Women's Hospital in Hamburg-Eppendorf clearly shows how important geriatric surgery has become. The immediate consequences are an increased workload for physicians, nursing staff and physical therapists."} {"id": "PMID:1261790", "title": "[Frequency of obstetrical operations and perinatal mortality before and after admission of continuous fetal monitoring (author's transl)].", "content": "Two groups of obstetrical patients were statistically analyzed with a computer. The first group A (2339 deliveries, January 1967-June 1968) was controlled by conservative obstetrical methods, the second group B (2512 deliveries, January 1973-June 1974) was controlled by continuous monitoring of fetal heart rate and by analysis of fetal blood during labour. The results of the statistical analysis can be summarized: 1. The frequency of obstetrical operations (vacuum, obstetrical forceps, Caesarean section) increases from 12.8% (group A) to 22.5% (group B). 2. The percentage of Caesarean sections decided on for the sake of the child rose from 45.7% (group A) to 54.7% (group B). 3. Vital indications fell due to increasingly preventive obstetrics from 54.3% to 45.3%. 4. The frequency of Caesarean sections rose due to increasing indication \"absolute or relative pelvic disproportion\" of the mediterranean patients. 5. However the analysis of fetal blood during labour and the continuous monitoring of fetal heart rate has prevented a further increase of Caesarean sections. 6. The increasing percentage of obstetric forceps was due to our intention of preventing prolonged labour. 7. Maternal mortality after operative delivery reached 0.04% in group A and 0% in group B. 8. Perinatal mortality of children, delivered by operation, has decreased from 3.0% (group A) to 0,7% (group B). 9. The Apgar scores after operative deliveries were much better in group B (continuous fetal monitoring) than in group A (without fetal monitoring).", "contents": "[Frequency of obstetrical operations and perinatal mortality before and after admission of continuous fetal monitoring (author's transl)]. Two groups of obstetrical patients were statistically analyzed with a computer. The first group A (2339 deliveries, January 1967-June 1968) was controlled by conservative obstetrical methods, the second group B (2512 deliveries, January 1973-June 1974) was controlled by continuous monitoring of fetal heart rate and by analysis of fetal blood during labour. The results of the statistical analysis can be summarized: 1. The frequency of obstetrical operations (vacuum, obstetrical forceps, Caesarean section) increases from 12.8% (group A) to 22.5% (group B). 2. The percentage of Caesarean sections decided on for the sake of the child rose from 45.7% (group A) to 54.7% (group B). 3. Vital indications fell due to increasingly preventive obstetrics from 54.3% to 45.3%. 4. The frequency of Caesarean sections rose due to increasing indication \"absolute or relative pelvic disproportion\" of the mediterranean patients. 5. However the analysis of fetal blood during labour and the continuous monitoring of fetal heart rate has prevented a further increase of Caesarean sections. 6. The increasing percentage of obstetric forceps was due to our intention of preventing prolonged labour. 7. Maternal mortality after operative delivery reached 0.04% in group A and 0% in group B. 8. Perinatal mortality of children, delivered by operation, has decreased from 3.0% (group A) to 0,7% (group B). 9. The Apgar scores after operative deliveries were much better in group B (continuous fetal monitoring) than in group A (without fetal monitoring)."} {"id": "PMID:1261791", "title": "[The monitoring of high risk pregnancies by determination of the estriol-16-glucoronide excretion. I. Methods and normal values (author's transl)].", "content": "A thin layer chromatographic method for the specific determination of estriol-16-glucoronide as azo dye is described. With this simple method the estriol excretion during pregnancy can be determined with omission of several steps in the determination such as the hydrolysis or evaporation of solvents. A single determination including the thin layer chromatography takes approximately 40 minutes. Based on 210 single determinations from the urine of pregnant women the normal range of excretion between the 28-42 week of pregnancy is determined. The mean excretion rises from 10.8 mg/24 hours at 28 weeks gestation to 25.8 mg/24 hours at 41 weeks gestation. The excretion of estriol-16-glucoronide is a measure of the estriol synthesis in the fetal-placental unit.", "contents": "[The monitoring of high risk pregnancies by determination of the estriol-16-glucoronide excretion. I. Methods and normal values (author's transl)]. A thin layer chromatographic method for the specific determination of estriol-16-glucoronide as azo dye is described. With this simple method the estriol excretion during pregnancy can be determined with omission of several steps in the determination such as the hydrolysis or evaporation of solvents. A single determination including the thin layer chromatography takes approximately 40 minutes. Based on 210 single determinations from the urine of pregnant women the normal range of excretion between the 28-42 week of pregnancy is determined. The mean excretion rises from 10.8 mg/24 hours at 28 weeks gestation to 25.8 mg/24 hours at 41 weeks gestation. The excretion of estriol-16-glucoronide is a measure of the estriol synthesis in the fetal-placental unit."} {"id": "PMID:1261792", "title": "[Hypersensitivity reaction associated with the use of Dextran 70 (Hiscon) in Hysteroscopy (author's transl)].", "content": "A hypersensitivity reaction to Dextran 70 during hysteroscopy for removal of an implanted Dalkon Shield is reported. The patient had not been exposed to Dextran previously and the hypersensitivity reaction was controlled by the administration of Benadryl, Solu-cortef and Phenergan. Since Dextran 70 is especially useful for hysteroscopy when bleeding is anticipated the possibility of enought Dextran uptake in the blood stream to cause a hypersensitivity reaction must be kept in mind during hysteroscopies with Dextran 70.", "contents": "[Hypersensitivity reaction associated with the use of Dextran 70 (Hiscon) in Hysteroscopy (author's transl)]. A hypersensitivity reaction to Dextran 70 during hysteroscopy for removal of an implanted Dalkon Shield is reported. The patient had not been exposed to Dextran previously and the hypersensitivity reaction was controlled by the administration of Benadryl, Solu-cortef and Phenergan. Since Dextran 70 is especially useful for hysteroscopy when bleeding is anticipated the possibility of enought Dextran uptake in the blood stream to cause a hypersensitivity reaction must be kept in mind during hysteroscopies with Dextran 70."} {"id": "PMID:1261793", "title": "[Mature intraligamentary pregnancy with florid salpingitis tuberculosa (author's transl)].", "content": "Reported is a case of a 32 year old para II where an intraligamentary extrauterine pregnancy was terminated by caesarean section at term following spontaneous rupture of the amniotic sack. The newborn male weighed 3600 g, there were no malformations. There was a transient phase of asphyxia. Histologic examination of the placenta, that had developed in the mesosalpinx, the Fallopian tube and the uterus that had been amputated supracervically, showed to our surprise a florid caseating tuberculosis of the mucosa of uterus and Fallopian tube and also in a circumscribed area of the basal plate. After an initial uneventful course the newborn developed clinical manifestations of connatal tuberculosis on the 16th day of life. Whereas the mother died a few days after delivery, the baby survived the infection, this certainly was due in large part to the prophylactic tuberculostatic treatment that had been initiated immediately after the diagnosis of tuberculosis was made on account of histology. The case of an extrauterine pregnancy at term reported here differs from most of the previous reports by a) the site of the pregnancy, b) the development of a mature living newborn without malformations and in respect to b) it differs from all previous publications by the existing active caseating tuberculous salpingitis and endometritis of the mother, and the connatal tuberculosis of the newborn with its successful treatment.", "contents": "[Mature intraligamentary pregnancy with florid salpingitis tuberculosa (author's transl)]. Reported is a case of a 32 year old para II where an intraligamentary extrauterine pregnancy was terminated by caesarean section at term following spontaneous rupture of the amniotic sack. The newborn male weighed 3600 g, there were no malformations. There was a transient phase of asphyxia. Histologic examination of the placenta, that had developed in the mesosalpinx, the Fallopian tube and the uterus that had been amputated supracervically, showed to our surprise a florid caseating tuberculosis of the mucosa of uterus and Fallopian tube and also in a circumscribed area of the basal plate. After an initial uneventful course the newborn developed clinical manifestations of connatal tuberculosis on the 16th day of life. Whereas the mother died a few days after delivery, the baby survived the infection, this certainly was due in large part to the prophylactic tuberculostatic treatment that had been initiated immediately after the diagnosis of tuberculosis was made on account of histology. The case of an extrauterine pregnancy at term reported here differs from most of the previous reports by a) the site of the pregnancy, b) the development of a mature living newborn without malformations and in respect to b) it differs from all previous publications by the existing active caseating tuberculous salpingitis and endometritis of the mother, and the connatal tuberculosis of the newborn with its successful treatment."} {"id": "PMID:1261794", "title": "[The decrease in the number of marriages (author's transl)].", "content": "Demographers adhere to the thesis that the increasing or decreasing incidence of marriage shows a statistical link to the existing number of males and females in the age group for marriage. For several years now it can be observed that this thesis requires revision. The number of marriages especially the number of marriages in those age groups in which the highest number of men and women absolutely and relatively get married decreases continually. At the same time the number of males and females in these groups increases. This development is a sign of an incipient disconnection of marriage from demographic data such as the number of persons in the age group for marriage and a disconnection for social and economic factors. Causes of this development are primarily the improvement of general education and the liberalization of sexual behavior. The traditional philosophy that all sexual intercourse should serve potential procreation is fading. The low rate of marriages and the low birth rate are signs of this development. Modern contraceptive methods facilitate this development of mature and autonomous persons but also opens a new complex area of new material and philosophical difficulties apart from the legal position of marriage for the protection of the partners and their offspring and for the social stability of their relationships.", "contents": "[The decrease in the number of marriages (author's transl)]. Demographers adhere to the thesis that the increasing or decreasing incidence of marriage shows a statistical link to the existing number of males and females in the age group for marriage. For several years now it can be observed that this thesis requires revision. The number of marriages especially the number of marriages in those age groups in which the highest number of men and women absolutely and relatively get married decreases continually. At the same time the number of males and females in these groups increases. This development is a sign of an incipient disconnection of marriage from demographic data such as the number of persons in the age group for marriage and a disconnection for social and economic factors. Causes of this development are primarily the improvement of general education and the liberalization of sexual behavior. The traditional philosophy that all sexual intercourse should serve potential procreation is fading. The low rate of marriages and the low birth rate are signs of this development. Modern contraceptive methods facilitate this development of mature and autonomous persons but also opens a new complex area of new material and philosophical difficulties apart from the legal position of marriage for the protection of the partners and their offspring and for the social stability of their relationships."} {"id": "PMID:1261795", "title": "[Ifosfamide in comparison with cyclophosphamide in advanced ovarian carcinomas (author's transl)].", "content": "Ifosfamide or cyclophosphamide was employed in an alternating series in 49 advanced ovarian carcinomas. The two cytostatic drugs were given in single massive doses. In primary inoperable ovarian carcinomas at stage III and IV a partial remission occurred in 8 of 19 cases (42%) after treatment with cyclophosphamide. Ifosfamide produced a partial or complete remission in 9 of 11 cases (82%). However, 3 patients treated by ifosfamide died within 3 weeks after the administration of the first massive dose. Regarding these cases as failures there was a remission in 9 of 14 cases (64%). Cyclophosphamide enabled a secondary radical operation in 7 of 19 (37%), ifosfamide in 6 of 14 cases (43%). The intervals between an exploratory laparotomy and the secondary radical operation were 5 months on the average for the two cytostatic drugs.", "contents": "[Ifosfamide in comparison with cyclophosphamide in advanced ovarian carcinomas (author's transl)]. Ifosfamide or cyclophosphamide was employed in an alternating series in 49 advanced ovarian carcinomas. The two cytostatic drugs were given in single massive doses. In primary inoperable ovarian carcinomas at stage III and IV a partial remission occurred in 8 of 19 cases (42%) after treatment with cyclophosphamide. Ifosfamide produced a partial or complete remission in 9 of 11 cases (82%). However, 3 patients treated by ifosfamide died within 3 weeks after the administration of the first massive dose. Regarding these cases as failures there was a remission in 9 of 14 cases (64%). Cyclophosphamide enabled a secondary radical operation in 7 of 19 (37%), ifosfamide in 6 of 14 cases (43%). The intervals between an exploratory laparotomy and the secondary radical operation were 5 months on the average for the two cytostatic drugs."} {"id": "PMID:1261796", "title": "Isolation and genetic analysis of mutant strains of Chlamydomonas reinhardi defective in gametic differentiation.", "content": "Impotent mutant strains of Chlamydomonas reinhardi, mating-type (mt) plus, are described that have normal growth and motility but fail to differentiate into normal gametes. Procedures for their isolation and their genetic analysis are described. Five of the imp strains (imp-2, imp-5, imp-l, imp-7, and imp-8) exhibit no flagellar agglutination when mixed with mt- or mt+ gametes and the mutations are shown to be unlinked to the mt locus (with the possible exception of imp-7). Two of the strains (imp-3 and imp-4) carry leaky mutations that affect cell fusion; neither mutation is found by tetrad analysis to be linked to mt or to the other. Cells of the imp-1 strain agglutinate well with mt- gametes and active agglutination continues for up to 48 hours, but cell fusion occurs only very rarely. Analysis of these rare zygotes indicates that imp-1 is closely linked to the mt+ locus, and fine-structural studies reveal that imp-1 gametes produce a mutant mating structure involved in zygotic cell fusion. The development of sexuality in C. reinhardi therefore appears amenable to genetic dissection.", "contents": "Isolation and genetic analysis of mutant strains of Chlamydomonas reinhardi defective in gametic differentiation. Impotent mutant strains of Chlamydomonas reinhardi, mating-type (mt) plus, are described that have normal growth and motility but fail to differentiate into normal gametes. Procedures for their isolation and their genetic analysis are described. Five of the imp strains (imp-2, imp-5, imp-l, imp-7, and imp-8) exhibit no flagellar agglutination when mixed with mt- or mt+ gametes and the mutations are shown to be unlinked to the mt locus (with the possible exception of imp-7). Two of the strains (imp-3 and imp-4) carry leaky mutations that affect cell fusion; neither mutation is found by tetrad analysis to be linked to mt or to the other. Cells of the imp-1 strain agglutinate well with mt- gametes and active agglutination continues for up to 48 hours, but cell fusion occurs only very rarely. Analysis of these rare zygotes indicates that imp-1 is closely linked to the mt+ locus, and fine-structural studies reveal that imp-1 gametes produce a mutant mating structure involved in zygotic cell fusion. The development of sexuality in C. reinhardi therefore appears amenable to genetic dissection."} {"id": "PMID:1261797", "title": "The unit of selection in Drosophila mercatorum. I. The interation of selection and meiosis in parthenogenetic strains.", "content": "An important problem in population genetics is the determination of the level of genetic organization to which fitness measures can be ascribed that yield an adequate description or prediction of the outcome of selection in populations. To study this problem, we used two strains of Drosophila merca torum (S-1-Im and O-3-Im) that are capable of both sexual and parthenogenetic reproduction, a feature that allows us to experimentally control many factors which affect genetic variability. Both S and O reproduce parthenogenetically by \"pronuclear duplication,\" a mechanism that retains normal meiosis (and hence crossing over and assortment) but results in homozygosity for all loci in a single generation. Since an isozyme survey indicated that S and O differ at a third of their loci, we hypothesized that S and O have adapted in genetically distinct fashions to the genetic environment of total homozygosity. This is tested by breeding females that are S-O hybrids for 100%, 60% and 40% of their genetic backgrounds, and scoring their respective pathenogenetic progenies for four isozyme and two visible markers. The data collected gave evidence for a coadaptation to total homozygosity involving non-additive and non-multiplicative interactions between non-alleles. As the perturbation of the parental coadapted genotypes by meiosis increases (i.e., the greater the degree of S-O hybridity), the level of genetic material which behaves as an additive/multiplicative fitness unit becomes larger. Selective neutrality of genetic variation may be an artifact of our failure to measure the proper genetic unit of selection.", "contents": "The unit of selection in Drosophila mercatorum. I. The interation of selection and meiosis in parthenogenetic strains. An important problem in population genetics is the determination of the level of genetic organization to which fitness measures can be ascribed that yield an adequate description or prediction of the outcome of selection in populations. To study this problem, we used two strains of Drosophila merca torum (S-1-Im and O-3-Im) that are capable of both sexual and parthenogenetic reproduction, a feature that allows us to experimentally control many factors which affect genetic variability. Both S and O reproduce parthenogenetically by \"pronuclear duplication,\" a mechanism that retains normal meiosis (and hence crossing over and assortment) but results in homozygosity for all loci in a single generation. Since an isozyme survey indicated that S and O differ at a third of their loci, we hypothesized that S and O have adapted in genetically distinct fashions to the genetic environment of total homozygosity. This is tested by breeding females that are S-O hybrids for 100%, 60% and 40% of their genetic backgrounds, and scoring their respective pathenogenetic progenies for four isozyme and two visible markers. The data collected gave evidence for a coadaptation to total homozygosity involving non-additive and non-multiplicative interactions between non-alleles. As the perturbation of the parental coadapted genotypes by meiosis increases (i.e., the greater the degree of S-O hybridity), the level of genetic material which behaves as an additive/multiplicative fitness unit becomes larger. Selective neutrality of genetic variation may be an artifact of our failure to measure the proper genetic unit of selection."} {"id": "PMID:1261798", "title": "A computer model allowing maintenance of large amounts of genetic variability in Mendelian populations. II. The balance of forces between linkage and random assortment.", "content": "It is shown, through theory and computer simulations of outbreeding Mendelian populations, that there may be conditions under which a balance is struck between two facotrs. The first is the advantage of random assortment, which will, when multilocus selection is for intermediate equilibrium values, lead to higher average heterozygosity than when linkage is introduced. There is some indication that random assortment is also advantageous when selection is toward a uniform distribution of equilibrium values. The second factor is the advantage of linkage between loci having positive epistatic interactions. When multilocus selection is for a bimodal distribution of equilibrium values an early advantage of random assortment is replaced by a later disadvantage. Linkage disequilibrium, which in finite populations is increased only by random or selective sampling, may hinder the movement of alleles to their selective equilibria, thus leading to the advantage of random assortment.-Some consequences of this approach to the structure of natural populations are discussed.", "contents": "A computer model allowing maintenance of large amounts of genetic variability in Mendelian populations. II. The balance of forces between linkage and random assortment. It is shown, through theory and computer simulations of outbreeding Mendelian populations, that there may be conditions under which a balance is struck between two facotrs. The first is the advantage of random assortment, which will, when multilocus selection is for intermediate equilibrium values, lead to higher average heterozygosity than when linkage is introduced. There is some indication that random assortment is also advantageous when selection is toward a uniform distribution of equilibrium values. The second factor is the advantage of linkage between loci having positive epistatic interactions. When multilocus selection is for a bimodal distribution of equilibrium values an early advantage of random assortment is replaced by a later disadvantage. Linkage disequilibrium, which in finite populations is increased only by random or selective sampling, may hinder the movement of alleles to their selective equilibria, thus leading to the advantage of random assortment.-Some consequences of this approach to the structure of natural populations are discussed."} {"id": "PMID:1261801", "title": "Total arthroplasty of the wrist to relieve pain and increase motion.", "content": "Total joint arthroplasty of the wrist is a feasible and satisfactory solution to the problems of patients who have significant wrist pain or severe limitation of motion, or both. It is particularly useful in patients with rheumatoid arthritis or with post-traumatic or degenerative arthritis of the wrist. In geriatric patients, this procedure appears to be a satisfactory alternative to wrist joint arthrodesis. Proper placement of the device and proper surgical technique to simulate the normal balance and motion of the wrist are necessary.", "contents": "Total arthroplasty of the wrist to relieve pain and increase motion. Total joint arthroplasty of the wrist is a feasible and satisfactory solution to the problems of patients who have significant wrist pain or severe limitation of motion, or both. It is particularly useful in patients with rheumatoid arthritis or with post-traumatic or degenerative arthritis of the wrist. In geriatric patients, this procedure appears to be a satisfactory alternative to wrist joint arthrodesis. Proper placement of the device and proper surgical technique to simulate the normal balance and motion of the wrist are necessary."} {"id": "PMID:1261804", "title": "Prevention of wound sepsis in joint replacement surgery.", "content": "Prevention of infection in the newer orthopedic procedures that involve implantation of large foreign bodies requires the establishment of routines and a policy of meticulous attention to detail. A careful preoperative examination, including identification of occult infections, is crucial. Then, uninfected patients who are selected for such surgery should receive prophylactic antimicrobial agents. The operating room technique includes rigid traffic control, strict aseptic precautions, protection of instruments from airborne contamination until the procedure is begun, and use of impermeable hoods and large masks by members of the surgical team. An iodophor skin preparation appears to achieve satisfactory skin asepsis. Although the use of unidirectional airflow or ultraviolet light reduces the level of airborne bacteria, these procedures have not been proved to be more effective than meticulous, carefully performed surgery in lowering rates of postoperative wound infection.", "contents": "Prevention of wound sepsis in joint replacement surgery. Prevention of infection in the newer orthopedic procedures that involve implantation of large foreign bodies requires the establishment of routines and a policy of meticulous attention to detail. A careful preoperative examination, including identification of occult infections, is crucial. Then, uninfected patients who are selected for such surgery should receive prophylactic antimicrobial agents. The operating room technique includes rigid traffic control, strict aseptic precautions, protection of instruments from airborne contamination until the procedure is begun, and use of impermeable hoods and large masks by members of the surgical team. An iodophor skin preparation appears to achieve satisfactory skin asepsis. Although the use of unidirectional airflow or ultraviolet light reduces the level of airborne bacteria, these procedures have not been proved to be more effective than meticulous, carefully performed surgery in lowering rates of postoperative wound infection."} {"id": "PMID:1261805", "title": "Influenza of age on chromatin transcription in murine tissues using a heterologous and an homologous RNA polymerase.", "content": "No gross changes in the compositions of chromatin prepared from liver, kidney and brain were noted with age. A decreased age-dependent in vitro chromatin template activity was observed using an Escherichia coli RNA polymerase. This was paralleled by a reduction in the number of initiation sites on the chromatin for the enzyme. However, using a homologous RNA polymerase definite age-related specificities in template activity were found. When chromatin and enzyme were 'age-matched', maximal activity was observed. This levle of activity was comparable in both 6 and 31-month-old mice, which suggested no impairment of function with age.", "contents": "Influenza of age on chromatin transcription in murine tissues using a heterologous and an homologous RNA polymerase. No gross changes in the compositions of chromatin prepared from liver, kidney and brain were noted with age. A decreased age-dependent in vitro chromatin template activity was observed using an Escherichia coli RNA polymerase. This was paralleled by a reduction in the number of initiation sites on the chromatin for the enzyme. However, using a homologous RNA polymerase definite age-related specificities in template activity were found. When chromatin and enzyme were 'age-matched', maximal activity was observed. This levle of activity was comparable in both 6 and 31-month-old mice, which suggested no impairment of function with age."} {"id": "PMID:1261806", "title": "The collagenous and non-collagenous protein of the canine intervertebral disc and their variation with age, spinal level and breed.", "content": "The total nitrogen, collagen and non-collagenous protein (NCP) content of the nucleus pulposus (NP), transitional zone (TZ) and annulus fibrosus (AF) of the beagle (a chondrodystrophoid breed) and greyhound (a non-chondrodystrophoid breed) intervertebral discs have been determined over the age range birth to 124 months. Discs were sampled at three spinal levels - lumbosacral, lumbar and thoracic regions. The beagle NP attains an average NP collagen content of 25% dry weight before 11 months of age, whereas the greyhound NP content is less than 5% collagen for most of its life. The NCP of the young greyhound disc is greater than that of the beagle of corresponding age. Plots of the ratio of collagen/NCP for discal regions at various ages highlight the large differences between the two breeds of dog. It is suggested that these differences in protein distribution are related to the elevated incidence of intervertebral disc prolapse in the beagle.", "contents": "The collagenous and non-collagenous protein of the canine intervertebral disc and their variation with age, spinal level and breed. The total nitrogen, collagen and non-collagenous protein (NCP) content of the nucleus pulposus (NP), transitional zone (TZ) and annulus fibrosus (AF) of the beagle (a chondrodystrophoid breed) and greyhound (a non-chondrodystrophoid breed) intervertebral discs have been determined over the age range birth to 124 months. Discs were sampled at three spinal levels - lumbosacral, lumbar and thoracic regions. The beagle NP attains an average NP collagen content of 25% dry weight before 11 months of age, whereas the greyhound NP content is less than 5% collagen for most of its life. The NCP of the young greyhound disc is greater than that of the beagle of corresponding age. Plots of the ratio of collagen/NCP for discal regions at various ages highlight the large differences between the two breeds of dog. It is suggested that these differences in protein distribution are related to the elevated incidence of intervertebral disc prolapse in the beagle."} {"id": "PMID:1261807", "title": "[Elaboration and standardization of a series of psychometric tests for old people (author's transl)].", "content": "We had previously elaborated a series of psychometric tests for old people. The aim of this test series is to assess the effects of brain-stimulating drugs (vasodilatating drugs). A factorial analysis was then carried out which enables us to reduce the number of tests, on the one hand, and to indicate the most fundamental fields of activity in old people, on the other hand. Four factors were distinguished. They assess respectively: watchfulness, memory, fluidity, and precision in the task undertaken. These four factors are strongly correlated. This implies the presence of a general factor, close in kind to the first factor. Watchfulness, attention and concentration are, in fact, necessary but insufficient conditions for the performance of all cognitive activities. A total of 7 tests among the most representative of each factor were retained. They are described in detail: test conditions, instructions, scoring and standardization.", "contents": "[Elaboration and standardization of a series of psychometric tests for old people (author's transl)]. We had previously elaborated a series of psychometric tests for old people. The aim of this test series is to assess the effects of brain-stimulating drugs (vasodilatating drugs). A factorial analysis was then carried out which enables us to reduce the number of tests, on the one hand, and to indicate the most fundamental fields of activity in old people, on the other hand. Four factors were distinguished. They assess respectively: watchfulness, memory, fluidity, and precision in the task undertaken. These four factors are strongly correlated. This implies the presence of a general factor, close in kind to the first factor. Watchfulness, attention and concentration are, in fact, necessary but insufficient conditions for the performance of all cognitive activities. A total of 7 tests among the most representative of each factor were retained. They are described in detail: test conditions, instructions, scoring and standardization."} {"id": "PMID:1261808", "title": "[Research and elaboration of a series of psychological tests for studying the quality of memory in old people (author's transl)].", "content": "Two series of mnesic tests were elaborated for experimental purposes by grouping and adapting traditional memory tests. The first set gives an overall study of the individual by assessing his short-term retention abilities. The second set is more specific and measures essentially his learning capabilities and the memorizing processes. These test series were designed to furnish both an instantaneous evaluation of the individual in relation to a group and a longitudinal evaluation of his abilities. Rather than assessing the mnesic capital, the test series evaluate the dynamic forms of memory expression which underlie every mnemonic operation, such as: memory span (or field of apprehension), retention processes, recognition, identification, spontaneous reminiscence, induced reminiscence (or associative memory), learning abilities on the basis of both concrete and practical as well as abstract and verbal material. They represent a psychometric tool permitting comparisons through a range of retests and quantifiable scoring of results. But they are also a clinical instrument, in the sense that the processes of the various intellectual functions can be qualitatively apprehended.", "contents": "[Research and elaboration of a series of psychological tests for studying the quality of memory in old people (author's transl)]. Two series of mnesic tests were elaborated for experimental purposes by grouping and adapting traditional memory tests. The first set gives an overall study of the individual by assessing his short-term retention abilities. The second set is more specific and measures essentially his learning capabilities and the memorizing processes. These test series were designed to furnish both an instantaneous evaluation of the individual in relation to a group and a longitudinal evaluation of his abilities. Rather than assessing the mnesic capital, the test series evaluate the dynamic forms of memory expression which underlie every mnemonic operation, such as: memory span (or field of apprehension), retention processes, recognition, identification, spontaneous reminiscence, induced reminiscence (or associative memory), learning abilities on the basis of both concrete and practical as well as abstract and verbal material. They represent a psychometric tool permitting comparisons through a range of retests and quantifiable scoring of results. But they are also a clinical instrument, in the sense that the processes of the various intellectual functions can be qualitatively apprehended."} {"id": "PMID:1261809", "title": "Light and electron microscopy of the ovarian interstitial tissue in the senile rat: normal aspect and response to HCG of \"deficiency cells' and 'epithelial cords'.", "content": "The two components of the interstitial tissue in the senile rat's ovary--deficiency cells and epithelial cellular cords--both contain steroidogenic organelles at a very low level of activity, which can be notably raised by HCG. Deficiency cells and epithelial cords are not the expression of primary ovarian aging, but the consequence of senile gonadotropic hypofunctioning. For that same reason, these ovarian structures become permanent and their possible cellular aging can thus be studied. No ultrastructural signs of senescence have as yet been observed.", "contents": "Light and electron microscopy of the ovarian interstitial tissue in the senile rat: normal aspect and response to HCG of \"deficiency cells' and 'epithelial cords'. The two components of the interstitial tissue in the senile rat's ovary--deficiency cells and epithelial cellular cords--both contain steroidogenic organelles at a very low level of activity, which can be notably raised by HCG. Deficiency cells and epithelial cords are not the expression of primary ovarian aging, but the consequence of senile gonadotropic hypofunctioning. For that same reason, these ovarian structures become permanent and their possible cellular aging can thus be studied. No ultrastructural signs of senescence have as yet been observed."} {"id": "PMID:1261810", "title": "Molecular mechanisms of ageing. A critique.", "content": "Two kinds of evidence, taken in conjunction, indicate that Orgel's theory is inapplicable to a wide range of disorders of senescence in man. The age dependence and the anatomical distribution of the lesions of such disorders imply a Burnet type 'forbidden clone' theory of ageing. We describe the difficulty of establishing Orgel's theory for any disorder of ageing in man.", "contents": "Molecular mechanisms of ageing. A critique. Two kinds of evidence, taken in conjunction, indicate that Orgel's theory is inapplicable to a wide range of disorders of senescence in man. The age dependence and the anatomical distribution of the lesions of such disorders imply a Burnet type 'forbidden clone' theory of ageing. We describe the difficulty of establishing Orgel's theory for any disorder of ageing in man."} {"id": "PMID:1261812", "title": "Death and drug treatment in a psychiatric hospital.", "content": "218 deaths occurring in a psychiatric hospital during a 3-year period were reviewed and their drug treatment was compared with that of a control group. 75% of the patients suffered from an organic psychosis. Patients received a mean of 2.4 different drugs on the day of death and only 23.6% of the prescriptions were for psychotropic drugs. 20 patients died suddenly and although more of these individuals had received tricyclic antidepressants and phenothiazines than their controls, these differences were not statistically significant.", "contents": "Death and drug treatment in a psychiatric hospital. 218 deaths occurring in a psychiatric hospital during a 3-year period were reviewed and their drug treatment was compared with that of a control group. 75% of the patients suffered from an organic psychosis. Patients received a mean of 2.4 different drugs on the day of death and only 23.6% of the prescriptions were for psychotropic drugs. 20 patients died suddenly and although more of these individuals had received tricyclic antidepressants and phenothiazines than their controls, these differences were not statistically significant."} {"id": "PMID:1261873", "title": "Cross-sectional-type weight reference values for village children under five years in Lesotho.", "content": "Cross-sectional-type reference values for weight attained are described for village children under five years in rural Lesotho (formerly Basutoland). Weight measurements derive from observations on 1317 children attending an Under-Fives clinic; it is estimated that 60-70% of the children under five in the catchment area were represented. 4585 weighings on boys and 4826 weighings for girls are included in the analysis. Figures of weight-for-age of boys and girls are given separately as centile distributions suitable for use on Growth Charts. Lesotho 50 centile approximates to 3 centile of British children and slightly exceeds 80% Harvard standard. Weight attained for age is similar, in both sexes, to reports from other less-priviledged urban and rural areas, emphasizing the relative importance of environmental as compared to genetic influences in determining weight-for-age in early childhood. It is suggested that the construction of locally-derived growth reference values is both appropriate and practicable.", "contents": "Cross-sectional-type weight reference values for village children under five years in Lesotho. Cross-sectional-type reference values for weight attained are described for village children under five years in rural Lesotho (formerly Basutoland). Weight measurements derive from observations on 1317 children attending an Under-Fives clinic; it is estimated that 60-70% of the children under five in the catchment area were represented. 4585 weighings on boys and 4826 weighings for girls are included in the analysis. Figures of weight-for-age of boys and girls are given separately as centile distributions suitable for use on Growth Charts. Lesotho 50 centile approximates to 3 centile of British children and slightly exceeds 80% Harvard standard. Weight attained for age is similar, in both sexes, to reports from other less-priviledged urban and rural areas, emphasizing the relative importance of environmental as compared to genetic influences in determining weight-for-age in early childhood. It is suggested that the construction of locally-derived growth reference values is both appropriate and practicable."} {"id": "PMID:1261874", "title": "Age-dependence of body weight and linear dimensions in adult Mus and Peromyscus.", "content": "Head plus body length (HBL), tail length (TL) and body weight (BW) were measured on two species of small myomorph rodents, Mus musculus and Peromyscus leucopus, throughout adult life. Both sexes of Mus show about a 15 per cent increase of HBL and TL between 5 and 24 months of age, and a BW increase of about 47 per cent. There is no age-trend of HBL in either sex of Peromyscus between 5 and 67 months of age, while TL increases about 7 per cent. In both species, cessation of skeletal growth is followed by a steady decrement of body mass, which averages about 0.23 per cent per month throughout adult life for the two sexes of Peromyscus, and over two per cent per month after cessation of skeletal growth in Mus. The weight loss in Mus in the last half of the lifespan is shown to be associated with age, rather than with the duration of subsequent survival. This evidence against the hypothesis that the late weight loss in Mus is due to terminal disease.", "contents": "Age-dependence of body weight and linear dimensions in adult Mus and Peromyscus. Head plus body length (HBL), tail length (TL) and body weight (BW) were measured on two species of small myomorph rodents, Mus musculus and Peromyscus leucopus, throughout adult life. Both sexes of Mus show about a 15 per cent increase of HBL and TL between 5 and 24 months of age, and a BW increase of about 47 per cent. There is no age-trend of HBL in either sex of Peromyscus between 5 and 67 months of age, while TL increases about 7 per cent. In both species, cessation of skeletal growth is followed by a steady decrement of body mass, which averages about 0.23 per cent per month throughout adult life for the two sexes of Peromyscus, and over two per cent per month after cessation of skeletal growth in Mus. The weight loss in Mus in the last half of the lifespan is shown to be associated with age, rather than with the duration of subsequent survival. This evidence against the hypothesis that the late weight loss in Mus is due to terminal disease."} {"id": "PMID:1261875", "title": "Alaskan malamute chondrodysplasia. I. Bone composition studies.", "content": "Chondrodysplastic Alaskan Malamutes exhibit concentrations of calcium, phosphorus and magnesium in radius, ulna, and humerus bone segments similar to those of non-chondrodysplastic dogs of similar age. Significant differences in extractability of mineral components with 5% EDTA were observed in specific bone segments. Although these data suggest that a primary derangement in calcium and phosphorus was possible the magnitude of the differences strongly suggested it unlikely and stress or mechanical factors may account for some of the observed differences. The possibility that chondrodysplasia provides a model for human disorders such as fibrogenesis imperfecta ossium was discussed. These data presented support a previous hypothesis that the chondrodysplasia is not a vitamin D-resistant rickets syndrome.", "contents": "Alaskan malamute chondrodysplasia. I. Bone composition studies. Chondrodysplastic Alaskan Malamutes exhibit concentrations of calcium, phosphorus and magnesium in radius, ulna, and humerus bone segments similar to those of non-chondrodysplastic dogs of similar age. Significant differences in extractability of mineral components with 5% EDTA were observed in specific bone segments. Although these data suggest that a primary derangement in calcium and phosphorus was possible the magnitude of the differences strongly suggested it unlikely and stress or mechanical factors may account for some of the observed differences. The possibility that chondrodysplasia provides a model for human disorders such as fibrogenesis imperfecta ossium was discussed. These data presented support a previous hypothesis that the chondrodysplasia is not a vitamin D-resistant rickets syndrome."} {"id": "PMID:1261876", "title": "Longitudinal growth of skeletal muscle fibres in lines of mice selected for high and low body weight.", "content": "The effect of selection for increased and decreased body weight on the weight, mean fibre length, mean estimated resting fibre length, mean sarcomere length and mean sarcomere number per fibre of the biceps brachii muscle was studied in 10 week old mice. The expected alterations in muscle weight were present and were due in part to changes in fibre length which was increased in the high line and decreased in the low line. The changes in fibre length were due to differences in sarcomere number per fibre which was increased in the high line and decreased in the low line. The mean sarcomere length of mice in the high and low lines did not differ significantly from control indicating that this parameter is unaffected by selection for altered body weight. It is suggested that genetic factors influence longitudinal muscle fibre growth in two ways. Species differ in the length of their myofilaments whereas differences between individuals and lines within a species are due to the formation of additional sarcomeres.", "contents": "Longitudinal growth of skeletal muscle fibres in lines of mice selected for high and low body weight. The effect of selection for increased and decreased body weight on the weight, mean fibre length, mean estimated resting fibre length, mean sarcomere length and mean sarcomere number per fibre of the biceps brachii muscle was studied in 10 week old mice. The expected alterations in muscle weight were present and were due in part to changes in fibre length which was increased in the high line and decreased in the low line. The changes in fibre length were due to differences in sarcomere number per fibre which was increased in the high line and decreased in the low line. The mean sarcomere length of mice in the high and low lines did not differ significantly from control indicating that this parameter is unaffected by selection for altered body weight. It is suggested that genetic factors influence longitudinal muscle fibre growth in two ways. Species differ in the length of their myofilaments whereas differences between individuals and lines within a species are due to the formation of additional sarcomeres."} {"id": "PMID:1261877", "title": "Serum protein concentrations and enzyme activities, as functions of age and sex, in Sinclair (S-1) miniature swine.", "content": "Venous blood samples were collected monthly from 60 male and 60 female Sinclair (S-1) miniature swine from 1 through 36 months of age. Serum total protein concentration increased linearly from 1 through 10 months of age and remained stable thereafter with no sex related difference. Serum albumin concentration decreased from 1 through 3 months, increased from 3 through 8 months and decreased from 14 through 36 months. From 2 through 36 months, serum alpha-globulin concentration decreased; whereas, serum beta-globulin concentration increased. Serum gamma-globulin concentration increased markedly from 1 through 3 months and continued to increase through 36 months of age. From 10 through 36 months, males had a greater mean serum gamma-globulin concentration than did females. Serum total globulin concentration increased most rapidly from 1 through 3 months, less rapidly from 3 through 18 months and remained stable thereafter. Serum albumin/globulin ratio decreased sharply from 1 through 3 months and continued to decrease from 6 through 36 months with females having a greater mean concentration than males. Serum glutamic-oxaloacetic transaminase activity decreased from 1 through 30 months with males having a greater mean activity than females from 7 through 36 months of age. Serum alkaline phosphatase activity decreased from 1 through 36 months of age with no sex related difference. Serum lactic dehydrogenase activity decreased from 1 through 30 months with females having a greater mean activity than males from 24 through 36 months of age.", "contents": "Serum protein concentrations and enzyme activities, as functions of age and sex, in Sinclair (S-1) miniature swine. Venous blood samples were collected monthly from 60 male and 60 female Sinclair (S-1) miniature swine from 1 through 36 months of age. Serum total protein concentration increased linearly from 1 through 10 months of age and remained stable thereafter with no sex related difference. Serum albumin concentration decreased from 1 through 3 months, increased from 3 through 8 months and decreased from 14 through 36 months. From 2 through 36 months, serum alpha-globulin concentration decreased; whereas, serum beta-globulin concentration increased. Serum gamma-globulin concentration increased markedly from 1 through 3 months and continued to increase through 36 months of age. From 10 through 36 months, males had a greater mean serum gamma-globulin concentration than did females. Serum total globulin concentration increased most rapidly from 1 through 3 months, less rapidly from 3 through 18 months and remained stable thereafter. Serum albumin/globulin ratio decreased sharply from 1 through 3 months and continued to decrease from 6 through 36 months with females having a greater mean concentration than males. Serum glutamic-oxaloacetic transaminase activity decreased from 1 through 30 months with males having a greater mean activity than females from 7 through 36 months of age. Serum alkaline phosphatase activity decreased from 1 through 36 months of age with no sex related difference. Serum lactic dehydrogenase activity decreased from 1 through 30 months with females having a greater mean activity than males from 24 through 36 months of age."} {"id": "PMID:1261878", "title": "Comparative findings on the skelic index of black and white children and youths residing in South Carolina.", "content": "This paper pertains to one facet of human body form, the relation of lower limbs to stem as quantified by the skelic index (lower limb height x 100/sitting height). The subjects were North American black and white pupils measured during 1974-1975 at elementary and high schools in Columbia, South Carolina. Females were measured at ages 9 and 13 years, males at ages 11 years and 15 years. At each childhood and adolescent age studied, skelic index means were considerably higher for the black than for the white pupils. Standard deviations and distances between spaced percentiles showed that variability of the skelic index at a given age was similar for white and black school pupils of South Carolina. Supplementary means for components of the skelic index indicated (1) black children and youths were shorter in sitting height than their white age peers, and (2) white children and youths were shorter in lower limb height than their black age peers. The skelic index of both ethnic groups increased between late childhood and mid-adolescence.", "contents": "Comparative findings on the skelic index of black and white children and youths residing in South Carolina. This paper pertains to one facet of human body form, the relation of lower limbs to stem as quantified by the skelic index (lower limb height x 100/sitting height). The subjects were North American black and white pupils measured during 1974-1975 at elementary and high schools in Columbia, South Carolina. Females were measured at ages 9 and 13 years, males at ages 11 years and 15 years. At each childhood and adolescent age studied, skelic index means were considerably higher for the black than for the white pupils. Standard deviations and distances between spaced percentiles showed that variability of the skelic index at a given age was similar for white and black school pupils of South Carolina. Supplementary means for components of the skelic index indicated (1) black children and youths were shorter in sitting height than their white age peers, and (2) white children and youths were shorter in lower limb height than their black age peers. The skelic index of both ethnic groups increased between late childhood and mid-adolescence."} {"id": "PMID:1261879", "title": "Growth of the pig: patterns of changes in electrolytes, water, and protein.", "content": "In 246 pigs studied from day of birth through week 12, mean plasma concentration of Na was 144.2; K, 3.89; and Cl, 103 mEq/1. Fifty-five pigs were analyzed for total body water (TBW), Na, K, Cl, protein, and fat. TBW was 83% fat-free wet weight (FFWW) at birth and declined, but not significantly, over the 12 weeks. Water content of tissues differed from each other as well as in the rates at which their water content changed. Concentration of electrolytes Na, K, Cl (mEg/100 g FFWW) decreased significantly in whole pig, viscera, brain, and skin; while Na increased and K and Cl decreased significantly in skeletal muscle. Of the tissues, skeletal muscle contributed 32% (fat-free tissue weight as per cent of total FFWW) at birth and 44% at week 12; and viscera, 15% at birth and 21% at week 12. The contribution of skeleton decreased over the same period from 22 to 15%, skin from 14 to 6%, and brain from 2 to 0.5%. The contribution of total water by the various organs changes in the same direction as the contribution to total FFWW. Na, K, Cl, and protein as a per cent of total in skin also show the same directional change. In skeletal muscle there was a decrease in conribution to total Na and Cl, but an increase to total K and protein. In the skeleton, except for protein, there is an increase in contribution of total Na, K, and Cl. There was a correlation of 0.99 and 0.94 between the sum of total Na and K in milliequivalents and TBW in millimeters for the whole pig and skeletal muscle respectively.", "contents": "Growth of the pig: patterns of changes in electrolytes, water, and protein. In 246 pigs studied from day of birth through week 12, mean plasma concentration of Na was 144.2; K, 3.89; and Cl, 103 mEq/1. Fifty-five pigs were analyzed for total body water (TBW), Na, K, Cl, protein, and fat. TBW was 83% fat-free wet weight (FFWW) at birth and declined, but not significantly, over the 12 weeks. Water content of tissues differed from each other as well as in the rates at which their water content changed. Concentration of electrolytes Na, K, Cl (mEg/100 g FFWW) decreased significantly in whole pig, viscera, brain, and skin; while Na increased and K and Cl decreased significantly in skeletal muscle. Of the tissues, skeletal muscle contributed 32% (fat-free tissue weight as per cent of total FFWW) at birth and 44% at week 12; and viscera, 15% at birth and 21% at week 12. The contribution of skeleton decreased over the same period from 22 to 15%, skin from 14 to 6%, and brain from 2 to 0.5%. The contribution of total water by the various organs changes in the same direction as the contribution to total FFWW. Na, K, Cl, and protein as a per cent of total in skin also show the same directional change. In skeletal muscle there was a decrease in conribution to total Na and Cl, but an increase to total K and protein. In the skeleton, except for protein, there is an increase in contribution of total Na, K, and Cl. There was a correlation of 0.99 and 0.94 between the sum of total Na and K in milliequivalents and TBW in millimeters for the whole pig and skeletal muscle respectively."} {"id": "PMID:1261880", "title": "Immunological studies in patients with Crohn's disease.", "content": "An investigation of immunological parameters was conducted in 38 patients with Crohn's disease. The immunological tests employed included skin tests with dinitrochlorobenzene and a battery of common skin test antigens, lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen, serum immunoglobulins, and absolute lymphocyte counts. Crohn's disease patients were divided into two groups, those treated with immunosuppressive drugs and those not receiving immunosuppressive medications. The latter group was subdivided into patients with active and inactive disease. Immunosuppressed patients with Crohn's disease did not develop sensitivity to dinitrochlorobenzene and had mildly depressed skin test reactivity to common skin test procedures. Non-immunosuppressed patients with active Crohn's disease also reacted less frequently to common skin test antigens, but 16 of 17 such patients developed sensitivity to dinitrochlorobenzene. Lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen was normal in all groups of patients with Crohn's disease. However, when suboptimal incubation periods were used with phytohaemagglutinin stimulation, there was a significant difference between Crohn's disease patients and controls. Serum immunoglobulin levels and absolute lymphocyte counts were normal in all Crohn's disease patients. We conclude that immunity in Crohn's disease is qualitatively normal.", "contents": "Immunological studies in patients with Crohn's disease. An investigation of immunological parameters was conducted in 38 patients with Crohn's disease. The immunological tests employed included skin tests with dinitrochlorobenzene and a battery of common skin test antigens, lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen, serum immunoglobulins, and absolute lymphocyte counts. Crohn's disease patients were divided into two groups, those treated with immunosuppressive drugs and those not receiving immunosuppressive medications. The latter group was subdivided into patients with active and inactive disease. Immunosuppressed patients with Crohn's disease did not develop sensitivity to dinitrochlorobenzene and had mildly depressed skin test reactivity to common skin test procedures. Non-immunosuppressed patients with active Crohn's disease also reacted less frequently to common skin test antigens, but 16 of 17 such patients developed sensitivity to dinitrochlorobenzene. Lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen was normal in all groups of patients with Crohn's disease. However, when suboptimal incubation periods were used with phytohaemagglutinin stimulation, there was a significant difference between Crohn's disease patients and controls. Serum immunoglobulin levels and absolute lymphocyte counts were normal in all Crohn's disease patients. We conclude that immunity in Crohn's disease is qualitatively normal."} {"id": "PMID:1261881", "title": "Gastrointestinal involvement in systemic mastocytosis.", "content": "Four consecutive patients with systemic mastocytosis were studied. One patient had a malabsorption syndrome with only minor histological changes of the intestinal mucosa. Another patient with ulcer diathesis had a gastric secretory pattern resembling Zollinger-Ellison syndrome. Serum gastrin and histamine levels were consistently normal in all patients. Endoscopy of stomach and colon disclosed urticaria-like papulae either spontaneously or after topical provocation in all patients. No increase of mast cells was found in multiple mucosal biopsies. A markedly increased gastric tissue content of histamine was found, however, in the three patients studied. The findings suggest that urticaria-like lesions associated with a high tissue content of histamine may be more important that hyperhistaminaemia in causing the various gastrointestinal symptoms.", "contents": "Gastrointestinal involvement in systemic mastocytosis. Four consecutive patients with systemic mastocytosis were studied. One patient had a malabsorption syndrome with only minor histological changes of the intestinal mucosa. Another patient with ulcer diathesis had a gastric secretory pattern resembling Zollinger-Ellison syndrome. Serum gastrin and histamine levels were consistently normal in all patients. Endoscopy of stomach and colon disclosed urticaria-like papulae either spontaneously or after topical provocation in all patients. No increase of mast cells was found in multiple mucosal biopsies. A markedly increased gastric tissue content of histamine was found, however, in the three patients studied. The findings suggest that urticaria-like lesions associated with a high tissue content of histamine may be more important that hyperhistaminaemia in causing the various gastrointestinal symptoms."} {"id": "PMID:1261882", "title": "Hepatitis-B surface antigen and cirrhosis in Iraq.", "content": "Hepatitis-B surface antigen was found in 58% of 64 patients with cirrhosis in Iraq using counter immunoelectrophoresis (CIE), radioimmunoassay (RIA), and three commercial haemagglutination tests--Auscell (Abbott Laboratories), Hepatest (Wellcome Reagents Ltd.), and Hepanosticon (Organon Teknika). CIE detected about half as many positives as the other methods; RIA was the most sensitive. The number of positive reactions was much higher than in any previously reported series of patients with cirrhosis and seven times higher than in a normal hospital control population.", "contents": "Hepatitis-B surface antigen and cirrhosis in Iraq. Hepatitis-B surface antigen was found in 58% of 64 patients with cirrhosis in Iraq using counter immunoelectrophoresis (CIE), radioimmunoassay (RIA), and three commercial haemagglutination tests--Auscell (Abbott Laboratories), Hepatest (Wellcome Reagents Ltd.), and Hepanosticon (Organon Teknika). CIE detected about half as many positives as the other methods; RIA was the most sensitive. The number of positive reactions was much higher than in any previously reported series of patients with cirrhosis and seven times higher than in a normal hospital control population."} {"id": "PMID:1261883", "title": "Hyperamylasaemia after duodenoscopy and retrograde cholangiopancreatography.", "content": "The salivary and pancreatic isoamylases of serum were determined separately in 234 cases of duodenoscopy and retrograde cholangiopancreatography. Successful pancreatic opacification was associated with pathologically high pancreatic serum amylase activities in 60% of the cases. Extensive opacification was associated with large increases of pancreatic serum isoamylases, the maximal rise recorded was 40 times the initial value. In spite of these striking chemical events only two patients developed clinical acute pancreatitis. There were some variations in pancreatic opacification and in the elevation of pancreatic serum amylase which seemed to depend upon the particular contrast material used. A rise of the salivary serum isoamylases caused pathologically high total serum amylase activities in 7% of the cases. High levels of pancreatic serum isoamylase activity before the time of examination did not result in any different pattern of hyperamylasaemia.", "contents": "Hyperamylasaemia after duodenoscopy and retrograde cholangiopancreatography. The salivary and pancreatic isoamylases of serum were determined separately in 234 cases of duodenoscopy and retrograde cholangiopancreatography. Successful pancreatic opacification was associated with pathologically high pancreatic serum amylase activities in 60% of the cases. Extensive opacification was associated with large increases of pancreatic serum isoamylases, the maximal rise recorded was 40 times the initial value. In spite of these striking chemical events only two patients developed clinical acute pancreatitis. There were some variations in pancreatic opacification and in the elevation of pancreatic serum amylase which seemed to depend upon the particular contrast material used. A rise of the salivary serum isoamylases caused pathologically high total serum amylase activities in 7% of the cases. High levels of pancreatic serum isoamylase activity before the time of examination did not result in any different pattern of hyperamylasaemia."} {"id": "PMID:1261884", "title": "Absorption of propranolol and practolol in Coeliac disease.", "content": "Plasma concentrations of propranolol and practolol were measured in patients with coeliac disease and normal subjects. The mean plasma propranolol concentration in the coeliac patients was higher throughout the period of study, the differences being significant at one, six, and eight hours. The plasma concentration profile of practolol in the coeliacs followed a similar pattern but lagged behind that of the normal subjects. A possible reason for these differences is an alteration in the rate of drug diffusion across the atrophic mucosa of the upper jejunum in coeliac disease. Analysis of the results of the propranolol study suggests that an increase in the rate of absorption combined with saturation of first pass extraction may account for the increased plasma concentrations of unchanged propranolol found in coeliac disease. These abnormalities of drug absorption do not appear to be related to the duration of treatment with a gluten free diet.", "contents": "Absorption of propranolol and practolol in Coeliac disease. Plasma concentrations of propranolol and practolol were measured in patients with coeliac disease and normal subjects. The mean plasma propranolol concentration in the coeliac patients was higher throughout the period of study, the differences being significant at one, six, and eight hours. The plasma concentration profile of practolol in the coeliacs followed a similar pattern but lagged behind that of the normal subjects. A possible reason for these differences is an alteration in the rate of drug diffusion across the atrophic mucosa of the upper jejunum in coeliac disease. Analysis of the results of the propranolol study suggests that an increase in the rate of absorption combined with saturation of first pass extraction may account for the increased plasma concentrations of unchanged propranolol found in coeliac disease. These abnormalities of drug absorption do not appear to be related to the duration of treatment with a gluten free diet."} {"id": "PMID:1261885", "title": "Relationship of serum gastrin response to lower oesophageal sphincter pressure.", "content": "The role of gastrin in controlling lower oesophageal sphincter pressure (LESP) has been examined by measurement of LESP and serum gastrin response to a test protein solution and a control solution in humans. Both solutions were associated with significant (P less than 0-005) rise in LESP, but serum gastrin rose significantly (P=0-05) only after the protein solution. The rise in serum gastrin after the protein solution preceded the rise in LESP by 30 minutes. These results suggest that the lower oesophageal sphincter response to feeding may be independent of protein and is unrelated to gastrin release.", "contents": "Relationship of serum gastrin response to lower oesophageal sphincter pressure. The role of gastrin in controlling lower oesophageal sphincter pressure (LESP) has been examined by measurement of LESP and serum gastrin response to a test protein solution and a control solution in humans. Both solutions were associated with significant (P less than 0-005) rise in LESP, but serum gastrin rose significantly (P=0-05) only after the protein solution. The rise in serum gastrin after the protein solution preceded the rise in LESP by 30 minutes. These results suggest that the lower oesophageal sphincter response to feeding may be independent of protein and is unrelated to gastrin release."} {"id": "PMID:1261886", "title": "Function of the anal sphincters in patients with intussusception of the rectum.", "content": "Patients with intussusception of the rectum--six with anal incontinence and nine continent--were examined with respect to the function of the anal sphincters. Anal pressure was recorded continuously during rest, during maximal voluntary squeezing of the anal muscles, and during gradual expansion of the rectum by means of a balloon inserted into the rectal ampulla. The maximal anal pressure at rest, which is mainly due to activity of the internal anal sphincter, was lower (P less than 0-001) in the incontinent patients (31 mmHg +/- 5-6) than the continent (67 mmHg +/- 4-3) and the former had significantly smaller relaxations of the internal sphincter upon rectal distension (P less than 0-05). The increase in anal pressure during voluntary squeezing, a function of the external sphincter, did not differ significantly compared with healthy subjects in either incontinent or continent patients. On the basis of the above findings, it is concluded that the function of the internal sphincter is impaired in the incontinent patients.", "contents": "Function of the anal sphincters in patients with intussusception of the rectum. Patients with intussusception of the rectum--six with anal incontinence and nine continent--were examined with respect to the function of the anal sphincters. Anal pressure was recorded continuously during rest, during maximal voluntary squeezing of the anal muscles, and during gradual expansion of the rectum by means of a balloon inserted into the rectal ampulla. The maximal anal pressure at rest, which is mainly due to activity of the internal anal sphincter, was lower (P less than 0-001) in the incontinent patients (31 mmHg +/- 5-6) than the continent (67 mmHg +/- 4-3) and the former had significantly smaller relaxations of the internal sphincter upon rectal distension (P less than 0-05). The increase in anal pressure during voluntary squeezing, a function of the external sphincter, did not differ significantly compared with healthy subjects in either incontinent or continent patients. On the basis of the above findings, it is concluded that the function of the internal sphincter is impaired in the incontinent patients."} {"id": "PMID:1261887", "title": "Potassium status of patients with cirrhosis.", "content": "Whole body potassium measurements were performed on 55 cirrhotic patients in different stages of the disease. They included 34 with alcoholic cirrhosis, 10 with cryptogenic cirrhosis, eight with chronic active hepatitis, and three with haemochromatosis. Serial measurements were carried out in 21 patients. The findings of this study indicate that: (1) the aetiology of the cirrhosis is important in determining the potassium status of cirrhotics, most alcoholics being depleted; (2) ascites and decompensation are usually associated with potassium depletion but compensated cirrhotics may also be depleted even when not receiving diuretics; (3) the initial potassium status, whether a cirrhotic be decompensated or not, is difficult to alter in the short term (six months). Marked changes in potassium status can occur in alcoholic patients studied over longer periods.", "contents": "Potassium status of patients with cirrhosis. Whole body potassium measurements were performed on 55 cirrhotic patients in different stages of the disease. They included 34 with alcoholic cirrhosis, 10 with cryptogenic cirrhosis, eight with chronic active hepatitis, and three with haemochromatosis. Serial measurements were carried out in 21 patients. The findings of this study indicate that: (1) the aetiology of the cirrhosis is important in determining the potassium status of cirrhotics, most alcoholics being depleted; (2) ascites and decompensation are usually associated with potassium depletion but compensated cirrhotics may also be depleted even when not receiving diuretics; (3) the initial potassium status, whether a cirrhotic be decompensated or not, is difficult to alter in the short term (six months). Marked changes in potassium status can occur in alcoholic patients studied over longer periods."} {"id": "PMID:1261889", "title": "Influence of specific dietary sugars on the jejunal mechanisms for glucose, galactose, and alpha-methyl glucoside absorption: evidence for multiple sugar carriers.", "content": "The effects of feeding glucose, galactose, and alpha-methyl glucoside on the kinetics of absorption of these sugars in the jejunum of the fasting rat were assessed by recently developed chemical and electrical methods for characterizing the electrogenic active transfer mechanisms in vivo. The parameters of 'apparent Km' (an index of carrier affinity) and Vmax (an index of the maximum jejunal transfer capacity) were obtained from the kinetic data to describe quantitatively the active transport mechanisms in rats fed their normal solid diet, in rats deprived of solid food for three days, and in rats deprived of solid food but allowed ad libitum access to isotonic solutions of glucose, galactose, or alpha-methyl glucoside for up to three days. Feeding the sugars to fasting rats produced complex differential effects on the 'apparent Km's' and Vmax's of the various transport mechanisms. The changes, although complex, can best be explained by alterations in the transport mechanisms per se rather than by non-specific changes in intestinal morphology or metabolism. The differential effects induced by the feeding sugars are further evidence for the concept that jejunal enterocytes possess multiple carriers or mechansims for the absorption of actively transported sugars in vivo. The multiple forms of the sugar carriers (isocarriers?) MAY BE INVOLVED IN THE FACULTATIVE RESPONSES OF THE ENTEROCYTES TO CHANGES IN THE DIETARY LEVELS OF SUGAR AND MAY BE IMPORTANT IN UNDERSTANDING THE INFLUENCES OF DISEASE AND NUTRITIONAL STATUS ON ABSORPTION PROCESSES IN MAN.", "contents": "Influence of specific dietary sugars on the jejunal mechanisms for glucose, galactose, and alpha-methyl glucoside absorption: evidence for multiple sugar carriers. The effects of feeding glucose, galactose, and alpha-methyl glucoside on the kinetics of absorption of these sugars in the jejunum of the fasting rat were assessed by recently developed chemical and electrical methods for characterizing the electrogenic active transfer mechanisms in vivo. The parameters of 'apparent Km' (an index of carrier affinity) and Vmax (an index of the maximum jejunal transfer capacity) were obtained from the kinetic data to describe quantitatively the active transport mechanisms in rats fed their normal solid diet, in rats deprived of solid food for three days, and in rats deprived of solid food but allowed ad libitum access to isotonic solutions of glucose, galactose, or alpha-methyl glucoside for up to three days. Feeding the sugars to fasting rats produced complex differential effects on the 'apparent Km's' and Vmax's of the various transport mechanisms. The changes, although complex, can best be explained by alterations in the transport mechanisms per se rather than by non-specific changes in intestinal morphology or metabolism. The differential effects induced by the feeding sugars are further evidence for the concept that jejunal enterocytes possess multiple carriers or mechansims for the absorption of actively transported sugars in vivo. The multiple forms of the sugar carriers (isocarriers?) MAY BE INVOLVED IN THE FACULTATIVE RESPONSES OF THE ENTEROCYTES TO CHANGES IN THE DIETARY LEVELS OF SUGAR AND MAY BE IMPORTANT IN UNDERSTANDING THE INFLUENCES OF DISEASE AND NUTRITIONAL STATUS ON ABSORPTION PROCESSES IN MAN."} {"id": "PMID:1261890", "title": "Haemangioma of median nerve causing carpal tunnel syndrome.", "content": "A case report of an intraneural haemangioma which occurred in a nineteen year old girl, with an acute clinical course. Intraneural haemangioma is a rare condition, but may be another cause of carpal tunnel syndrome.", "contents": "Haemangioma of median nerve causing carpal tunnel syndrome. A case report of an intraneural haemangioma which occurred in a nineteen year old girl, with an acute clinical course. Intraneural haemangioma is a rare condition, but may be another cause of carpal tunnel syndrome."} {"id": "PMID:1261891", "title": "The contracting fibroblast as a clue to Dupuytren's contracture.", "content": "Examination of fibrous tissue from various sites in the palm reveals the presence of myofibroblasts only in the nodules, underlining their primary role in the production of contracture.", "contents": "The contracting fibroblast as a clue to Dupuytren's contracture. Examination of fibrous tissue from various sites in the palm reveals the presence of myofibroblasts only in the nodules, underlining their primary role in the production of contracture."} {"id": "PMID:1261892", "title": "Flexor synovectomy in the rheumatoid hand.", "content": "A review of the types, signs and symptoms of synovitis of the flexor surface of the hand. Indications, contra-indications and the results of surgery are discussed.", "contents": "Flexor synovectomy in the rheumatoid hand. A review of the types, signs and symptoms of synovitis of the flexor surface of the hand. Indications, contra-indications and the results of surgery are discussed."} {"id": "PMID:1261893", "title": "Unusual congenital anomalies of the thumb extensors. Report of two cases.", "content": "A case of rare hereditary anomaly of the extensor tendons of the thumb and a case of congenital duck-neck deformity of the thumb are reported.", "contents": "Unusual congenital anomalies of the thumb extensors. Report of two cases. A case of rare hereditary anomaly of the extensor tendons of the thumb and a case of congenital duck-neck deformity of the thumb are reported."} {"id": "PMID:1261894", "title": "Repair of the dorsal apparatus of the finger.", "content": "This paper describes a simple method of assessing the constituent features of flexion deformities of the proximal interphalangeal joints in Hansen's disease, and a simple operation to correct the anterior displacement of the lateral band and the associated contractures.", "contents": "Repair of the dorsal apparatus of the finger. This paper describes a simple method of assessing the constituent features of flexion deformities of the proximal interphalangeal joints in Hansen's disease, and a simple operation to correct the anterior displacement of the lateral band and the associated contractures."} {"id": "PMID:1261895", "title": "Contracture of fingers due to fixation of the flexor profundus digitorum to the ulna.", "content": "Two cases are reported where limitation of extension of one or more fingers resulted from fixation of the flexor profundus digitorum to the ring finger at the site of a fracture of the ulna.", "contents": "Contracture of fingers due to fixation of the flexor profundus digitorum to the ulna. Two cases are reported where limitation of extension of one or more fingers resulted from fixation of the flexor profundus digitorum to the ring finger at the site of a fracture of the ulna."} {"id": "PMID:1261896", "title": "A complication of distal interphalangeal joint arthrodesis.", "content": "The authors report the appearance of a swan-neck deformity few months after arthrodesis of the distal interphalangeal joint. The pathomechanics, prevention and treatment of the established deformity are discussed.", "contents": "A complication of distal interphalangeal joint arthrodesis. The authors report the appearance of a swan-neck deformity few months after arthrodesis of the distal interphalangeal joint. The pathomechanics, prevention and treatment of the established deformity are discussed."} {"id": "PMID:1261897", "title": "Restoration of pinch grip in traumatic ulnar palsy.", "content": "This paper reports tendon transfers carried out to restore the pinch grip in thirty-four patients with irreparable traumatic ulnar palsy. The advantages and disadvantages of the procedure are discussed. Performed for proper indications the results show improved function in most patients.", "contents": "Restoration of pinch grip in traumatic ulnar palsy. This paper reports tendon transfers carried out to restore the pinch grip in thirty-four patients with irreparable traumatic ulnar palsy. The advantages and disadvantages of the procedure are discussed. Performed for proper indications the results show improved function in most patients."} {"id": "PMID:1261898", "title": "Post-traumatic neurodystrophy. Treatment by corticosteroids.", "content": "This paper reports the results with corticosteroid therapy given to patients with neurodystrophy who failed to improve on other treatment, including intensive physiotherapy.", "contents": "Post-traumatic neurodystrophy. Treatment by corticosteroids. This paper reports the results with corticosteroid therapy given to patients with neurodystrophy who failed to improve on other treatment, including intensive physiotherapy."} {"id": "PMID:1261899", "title": "Bennett's fracture.", "content": "A new method of conservative treatment of Bennett's fracture is presented, the thumb being immobilised in moderate adduction rather than radial abduction. Anatomical dissections are outlined to demonstrate the rationale of this procedure.", "contents": "Bennett's fracture. A new method of conservative treatment of Bennett's fracture is presented, the thumb being immobilised in moderate adduction rather than radial abduction. Anatomical dissections are outlined to demonstrate the rationale of this procedure."} {"id": "PMID:1261900", "title": "Subcutaneous emphysema in a finger following an injection injury.", "content": "This is a case report of surgical emphysema in a finger resulting from a high velocity injection accident.", "contents": "Subcutaneous emphysema in a finger following an injection injury. This is a case report of surgical emphysema in a finger resulting from a high velocity injection accident."} {"id": "PMID:1261901", "title": "Observations on the use of silicone rubber spacers in tendon graft surgery.", "content": "Lessons learned from the use of silicone rubber spacers for the preparation of tendon graft beds in sixty digits are reported.", "contents": "Observations on the use of silicone rubber spacers in tendon graft surgery. Lessons learned from the use of silicone rubber spacers for the preparation of tendon graft beds in sixty digits are reported."} {"id": "PMID:1261902", "title": "Thorn-induced granulomata of bone.", "content": "A case of thorn-induced granuloma of bone is presented and discussed in relation to the previous eight cases reported. The condition affects the exposed areas, usually the hands, of children. It may be as long as nine months from the initial episode of injury or inflammation to presentation as pseudo-tumour. The radiographic appearance are those of a chronic granuloma with longitudinal cavitation and adjacent perioseal reaction and as such can be differentiated from Ewing's sarcoma, osteoid osteoma, tuberculosis dactylitis, benign osteoblastoma, and stress fracture.", "contents": "Thorn-induced granulomata of bone. A case of thorn-induced granuloma of bone is presented and discussed in relation to the previous eight cases reported. The condition affects the exposed areas, usually the hands, of children. It may be as long as nine months from the initial episode of injury or inflammation to presentation as pseudo-tumour. The radiographic appearance are those of a chronic granuloma with longitudinal cavitation and adjacent perioseal reaction and as such can be differentiated from Ewing's sarcoma, osteoid osteoma, tuberculosis dactylitis, benign osteoblastoma, and stress fracture."} {"id": "PMID:1261903", "title": "Digital flexor tendon irrigation.", "content": "A readily available standard intravenous cannular has proved to be a useful conduit for the irrigation of a digital flexor tendon.", "contents": "Digital flexor tendon irrigation. A readily available standard intravenous cannular has proved to be a useful conduit for the irrigation of a digital flexor tendon."} {"id": "PMID:1261904", "title": "The open palm and digit technique in the treatment of Dupuytren's contracture.", "content": "The authors have used the open palm and digit technique for Dupuytren's contracture in fifty-four patients since May, 1973. The procedure consists in making transverse skin incisions on the palm and fingers leaving the wounds open after limited fasciectomy. The results have been surprisingly good due to the elimination of haematoma formation and finger oedema, and the excellent quality of the final scar.", "contents": "The open palm and digit technique in the treatment of Dupuytren's contracture. The authors have used the open palm and digit technique for Dupuytren's contracture in fifty-four patients since May, 1973. The procedure consists in making transverse skin incisions on the palm and fingers leaving the wounds open after limited fasciectomy. The results have been surprisingly good due to the elimination of haematoma formation and finger oedema, and the excellent quality of the final scar."} {"id": "PMID:1261905", "title": "Reconstruction of the mutilated hand.", "content": "The experience gained from the reconstruction of sixty-seven severely mutilated hands is applied to the analysis of the procedures of choice in three groups of injury.", "contents": "Reconstruction of the mutilated hand. The experience gained from the reconstruction of sixty-seven severely mutilated hands is applied to the analysis of the procedures of choice in three groups of injury."} {"id": "PMID:1261906", "title": "Percutaneous internal fixation of fractures of the proximal phalanges.", "content": "A rational methods for management of the fractures of the proximal phalanges is presented. By this technique fracture healing and recovery of movement take place concurrently rather than consecutively thereby the morbidity is greatly reduced. It leads to early and complete rehabilitation of the patient in a short period.", "contents": "Percutaneous internal fixation of fractures of the proximal phalanges. A rational methods for management of the fractures of the proximal phalanges is presented. By this technique fracture healing and recovery of movement take place concurrently rather than consecutively thereby the morbidity is greatly reduced. It leads to early and complete rehabilitation of the patient in a short period."} {"id": "PMID:1261907", "title": "Hand injuries due to soccer.", "content": "Fifty-two hand injuries due to soccer were seen in one season. Approximately one-third of these were in goalkeepers, due mainly to contact with the ball; two-third were in other members of the team, due to either contact with a player or the ground.", "contents": "Hand injuries due to soccer. Fifty-two hand injuries due to soccer were seen in one season. Approximately one-third of these were in goalkeepers, due mainly to contact with the ball; two-third were in other members of the team, due to either contact with a player or the ground."} {"id": "PMID:1261951", "title": "[Diagnosis of breast carcinoma with thermographic methods: tele-thermovision, plate thermography].", "content": "The diagnosis of carcinoma of the mamma with the aid of tele-thermovision and liquid-crystal-thermography A review is given on thermographic diagnosis of carcinomas of the mamma with the aid of tele-thermovision and liquid-crystal-thermography. 132 carcinoma cases were microscopically examined with cytomorphological criteria. The microscopic and thermographic results were compared. The thermographic diagnosis \"suspicious\" is dependent on the diameter of the tumour, the vascularisation, the essential cytomorphological criteria as mitosis, prominence and size of nucleoli as well as deviation of the nucleous/plasma ratio. There was no dependence on the distance of the tumour from the surface of the breast and even on the perifocal infiltration with lymphoid cells. The accuracy rate in diagnosis with liquid-crystal-thermography is about 74%; false negative and false positive results both are about 9%. The accuracy rate for tele-thermovision is about 10% lower. The detection rate of carcinoma stage T1 ranges around 50%.", "contents": "[Diagnosis of breast carcinoma with thermographic methods: tele-thermovision, plate thermography]. The diagnosis of carcinoma of the mamma with the aid of tele-thermovision and liquid-crystal-thermography A review is given on thermographic diagnosis of carcinomas of the mamma with the aid of tele-thermovision and liquid-crystal-thermography. 132 carcinoma cases were microscopically examined with cytomorphological criteria. The microscopic and thermographic results were compared. The thermographic diagnosis \"suspicious\" is dependent on the diameter of the tumour, the vascularisation, the essential cytomorphological criteria as mitosis, prominence and size of nucleoli as well as deviation of the nucleous/plasma ratio. There was no dependence on the distance of the tumour from the surface of the breast and even on the perifocal infiltration with lymphoid cells. The accuracy rate in diagnosis with liquid-crystal-thermography is about 74%; false negative and false positive results both are about 9%. The accuracy rate for tele-thermovision is about 10% lower. The detection rate of carcinoma stage T1 ranges around 50%."} {"id": "PMID:1261952", "title": "[Frequency of local recidivism in breast carcinoma].", "content": "Frequency of local recidivation in carcinoma of the female breast represents a good parameter for the success of primary surgical treatment. A comparative study on nonselected patients of the Chir. Univ.-Klinik T\u00fcbingen showed, that local relapse of breast cancer did not increase after a conservative surgery due to different stages of carcinoma if: 1. the safety distance to the tumor was sufficient, 2. postoperative irradiation had been applied in megavolt technique. According to our results and regarding the 10-year-survival rate as well as the rate of local recidivation it does not seem imperative any longer to see a rigid indication for radical mastectomy.", "contents": "[Frequency of local recidivism in breast carcinoma]. Frequency of local recidivation in carcinoma of the female breast represents a good parameter for the success of primary surgical treatment. A comparative study on nonselected patients of the Chir. Univ.-Klinik T\u00fcbingen showed, that local relapse of breast cancer did not increase after a conservative surgery due to different stages of carcinoma if: 1. the safety distance to the tumor was sufficient, 2. postoperative irradiation had been applied in megavolt technique. According to our results and regarding the 10-year-survival rate as well as the rate of local recidivation it does not seem imperative any longer to see a rigid indication for radical mastectomy."} {"id": "PMID:1261953", "title": "[Cytological diagnosis of endometrial carcinoma].", "content": "Because of increase of endometrial carcinoma the frequency rate of invasive cervix carcinoma and carcinoma of uterine corpus has been changing in the last ten years and at several places in the world it is approaching 1:1. That shows the importance of early detection of endometrial carcinoma. A summary of cytology diagnostic of normal and pathological endometrium is given. Especially it is pointed to the great difference between the cytomorphical cell criteria of endometrial malignancies dependent on the differentiation grade of endometrial carcinoma. The predominance of cell atypia is found by the undifferentiated carcinoma of uterine corpus whereas the cells of frequently found well differentiated endometrial carcinoma often cannot be differentiated from normal endometrium cells. The observation of cells of endometrial carcinoma in normal cellular samples of cervix and vagina is no more than 60--70 percent; at this rate the endocervical aspiration has the greatest chance of detection. To correct the early cellular diagnosis of uterine carcinoma the appearance of normal endometrium cells by screening must be noticed and each finding at an untypical moment, for example in postmenopause, must be an alarm signal. The different intrauterine aspiration techniques obtained more than 90 percent accuracy in the detection of endometrial carcinoma. This method is qualified for special indications in a limited number of cases.", "contents": "[Cytological diagnosis of endometrial carcinoma]. Because of increase of endometrial carcinoma the frequency rate of invasive cervix carcinoma and carcinoma of uterine corpus has been changing in the last ten years and at several places in the world it is approaching 1:1. That shows the importance of early detection of endometrial carcinoma. A summary of cytology diagnostic of normal and pathological endometrium is given. Especially it is pointed to the great difference between the cytomorphical cell criteria of endometrial malignancies dependent on the differentiation grade of endometrial carcinoma. The predominance of cell atypia is found by the undifferentiated carcinoma of uterine corpus whereas the cells of frequently found well differentiated endometrial carcinoma often cannot be differentiated from normal endometrium cells. The observation of cells of endometrial carcinoma in normal cellular samples of cervix and vagina is no more than 60--70 percent; at this rate the endocervical aspiration has the greatest chance of detection. To correct the early cellular diagnosis of uterine carcinoma the appearance of normal endometrium cells by screening must be noticed and each finding at an untypical moment, for example in postmenopause, must be an alarm signal. The different intrauterine aspiration techniques obtained more than 90 percent accuracy in the detection of endometrial carcinoma. This method is qualified for special indications in a limited number of cases."} {"id": "PMID:1261954", "title": "[Leptothrix vaginalis. Morphological studies].", "content": "73 patients with a microscopically confirmed Leptothrix vaginalis-infection were examined clinically and cytologically. 80% of the cases showed Leptothrix alone or together wihh lactobacilli or cocci. 18% had trichomonas- and 2% candida-infections. 26 cases (34%) showed inflammation of the vagina. The majority of infection was found in the age group 26 to 45 years. A microscopical examination of the Leptothrix-filaments revealed a subtile segmentation and sporulation.", "contents": "[Leptothrix vaginalis. Morphological studies]. 73 patients with a microscopically confirmed Leptothrix vaginalis-infection were examined clinically and cytologically. 80% of the cases showed Leptothrix alone or together wihh lactobacilli or cocci. 18% had trichomonas- and 2% candida-infections. 26 cases (34%) showed inflammation of the vagina. The majority of infection was found in the age group 26 to 45 years. A microscopical examination of the Leptothrix-filaments revealed a subtile segmentation and sporulation."} {"id": "PMID:1261955", "title": "[Mental and neurological disorders associated with heart operations. Pre- and postoperative studies].", "content": "Long before the era of heart surgery began, \"cardiac psychoses\" were known and described. They do not differ at all from postoperative psychoses after heart-surgery. On the other hand heart-surgery carries a far higher incidence of psychiatric complications than general surgery (general surgery 0,1--1,0%; heart surgery 10--60%). There is no reason to believe that the intensive care unit plays a decisive role in the origin of postoperative cardiac psychoses. Among 150 patients there were 60=40%, who did not show any psychiatric symptoms after surgery. These were exposed to the same environment of the intensive care unit as were the patients who developped symptoms. There were however correlations of statistical significance between \"cardiac psychoses\" and 1. an occurrence of endogenous psychoses in the family with first degree relatives or in the life history of the patient himself, 2 higher grade of severity of heart disease, 3. extra corporal circulation, 4. higher age, 5. male sex. Postoperative cardiac psychoses are mainly of the type of exogenous psychoses (akuter exogener Reaktionstyp Bonhoeffer). There is no doubt that psychological, reactive and environmental factors do play a certain role too. This is shown by the character of delusions and hallucinations which frequently reflect the postoperative situation. Persecutory delusions with the fear of being killed and ideas and fears of severe body mutilation are the most common motives. Similar motives are frequently observed in postoperative dreams. The manifestations of mental disease in the family or personal history of the patient is considered a significant presupposition of developing a cardiac psychosis of the type of endogenous depression, acute delirium or with schizophrenia like delusions.", "contents": "[Mental and neurological disorders associated with heart operations. Pre- and postoperative studies]. Long before the era of heart surgery began, \"cardiac psychoses\" were known and described. They do not differ at all from postoperative psychoses after heart-surgery. On the other hand heart-surgery carries a far higher incidence of psychiatric complications than general surgery (general surgery 0,1--1,0%; heart surgery 10--60%). There is no reason to believe that the intensive care unit plays a decisive role in the origin of postoperative cardiac psychoses. Among 150 patients there were 60=40%, who did not show any psychiatric symptoms after surgery. These were exposed to the same environment of the intensive care unit as were the patients who developped symptoms. There were however correlations of statistical significance between \"cardiac psychoses\" and 1. an occurrence of endogenous psychoses in the family with first degree relatives or in the life history of the patient himself, 2 higher grade of severity of heart disease, 3. extra corporal circulation, 4. higher age, 5. male sex. Postoperative cardiac psychoses are mainly of the type of exogenous psychoses (akuter exogener Reaktionstyp Bonhoeffer). There is no doubt that psychological, reactive and environmental factors do play a certain role too. This is shown by the character of delusions and hallucinations which frequently reflect the postoperative situation. Persecutory delusions with the fear of being killed and ideas and fears of severe body mutilation are the most common motives. Similar motives are frequently observed in postoperative dreams. The manifestations of mental disease in the family or personal history of the patient is considered a significant presupposition of developing a cardiac psychosis of the type of endogenous depression, acute delirium or with schizophrenia like delusions."} {"id": "PMID:1261956", "title": "[Anterior cervical intervertebral disk operation without secondary fusion. Clinical and experimental studies].", "content": "The problems of the spontaneous fusion after cervical discectomy were studied in 12 patients. An examination after the operation showed an improvement of the neurological-radicular symptoms, but 75% of the patients complained about severe pains in the area of neck and shoulders. The cause of these complaints was found by radiological examination to be an angular kyphosis of the cervical spine combined with the subluxation of the intervertebral joints in the operated segment. The mechanical results of the ventral fusion without using interponates are being experimentally reproduced and evaluated. By comparing both methods, the method using interponates showed better results. Therefore, the discectomy with fusion using interponates should be preferred.", "contents": "[Anterior cervical intervertebral disk operation without secondary fusion. Clinical and experimental studies]. The problems of the spontaneous fusion after cervical discectomy were studied in 12 patients. An examination after the operation showed an improvement of the neurological-radicular symptoms, but 75% of the patients complained about severe pains in the area of neck and shoulders. The cause of these complaints was found by radiological examination to be an angular kyphosis of the cervical spine combined with the subluxation of the intervertebral joints in the operated segment. The mechanical results of the ventral fusion without using interponates are being experimentally reproduced and evaluated. By comparing both methods, the method using interponates showed better results. Therefore, the discectomy with fusion using interponates should be preferred."} {"id": "PMID:1261957", "title": "[Preventive psychotherapy for prevention of stealing].", "content": "In order to prevent patients from stealing, two categories of delinquents are to be taken into consideration: Those who suffer from somatic diseases and psychoses, e.g. prophyria, hypoglycemia, hebephrenia, schizophrenia, depression, mania or epileptic semiconscious states must be treated according to the basic sickness and by means of a supporting psychotherapy. In court exculpation should be recommended. Other people who fell the urge to steal are psychosocially disturbed. This may begin with lying, bad results at school and during professional or university training, and sometimes with running away from home. As soon as the family doctor observes these or similar phenomena, he should inform the parents, in order to start a preventive therapy of the family together with the prospective thief.", "contents": "[Preventive psychotherapy for prevention of stealing]. In order to prevent patients from stealing, two categories of delinquents are to be taken into consideration: Those who suffer from somatic diseases and psychoses, e.g. prophyria, hypoglycemia, hebephrenia, schizophrenia, depression, mania or epileptic semiconscious states must be treated according to the basic sickness and by means of a supporting psychotherapy. In court exculpation should be recommended. Other people who fell the urge to steal are psychosocially disturbed. This may begin with lying, bad results at school and during professional or university training, and sometimes with running away from home. As soon as the family doctor observes these or similar phenomena, he should inform the parents, in order to start a preventive therapy of the family together with the prospective thief."} {"id": "PMID:1261958", "title": "[Hypoglycemia. Part 4. General causes, physiological newborn hyperglycemia, hyperglycemia in various illnesses, metabolic deficiency, and metabolic error].", "content": "The possible causes for hypoglycemia are discussed in relation to the biochemical and metabolic basis of blood glucose regulation. The functional tests which are important for purposes of differential diagnosis are described in detail. Most cases of clinically important hypoglycemia are based on disfunctions of the regulatory endocrinological mechanisms necessary for prevention of hypoglycemia in the fasting state. The consequence, therefore, is a \"starvation hypoglycemia\". Ketosis during hypoglycemia is evaluated as a kind of \"glucose-sparing-mechanism\". It is observed in all cases, where the nutritional glucose supply is not sufficient. The common therapy in typical cases of starvation hypoglycemia is a carbohydrate rich and protein rich nutrition. Additionally, small and frequent meals are required for avoidance of starvation hypoglycemia. Whereas starvation hypoglycemia is frequently seen, so called reactive hypoglycemia is very rare. The following metabolic disorders lead to reactive hypoglycemia: leucinsensitive hypoglycemia, fructose intolerance, galactose intolerance, fructose-1,6-diphosphatase deficiency. Considering these cases special tolerance tests are required. With the usual routine test methods only leucin-sensitive hypoglycemia is diagnosed.", "contents": "[Hypoglycemia. Part 4. General causes, physiological newborn hyperglycemia, hyperglycemia in various illnesses, metabolic deficiency, and metabolic error]. The possible causes for hypoglycemia are discussed in relation to the biochemical and metabolic basis of blood glucose regulation. The functional tests which are important for purposes of differential diagnosis are described in detail. Most cases of clinically important hypoglycemia are based on disfunctions of the regulatory endocrinological mechanisms necessary for prevention of hypoglycemia in the fasting state. The consequence, therefore, is a \"starvation hypoglycemia\". Ketosis during hypoglycemia is evaluated as a kind of \"glucose-sparing-mechanism\". It is observed in all cases, where the nutritional glucose supply is not sufficient. The common therapy in typical cases of starvation hypoglycemia is a carbohydrate rich and protein rich nutrition. Additionally, small and frequent meals are required for avoidance of starvation hypoglycemia. Whereas starvation hypoglycemia is frequently seen, so called reactive hypoglycemia is very rare. The following metabolic disorders lead to reactive hypoglycemia: leucinsensitive hypoglycemia, fructose intolerance, galactose intolerance, fructose-1,6-diphosphatase deficiency. Considering these cases special tolerance tests are required. With the usual routine test methods only leucin-sensitive hypoglycemia is diagnosed."} {"id": "PMID:1261959", "title": "[Therapy of ulcus ventriculi with Caved-S. Use of the gastrocamera for diagnosis and control of therapy].", "content": "36 patients with a ventricular ulcer demonstrated by endoscopy and secured by histology, were given 2 tablets Caved-S 4 times a day for 4 weeks. Clinical parameters were subjective complaints, such as pain and heartburn, which after a relatively short time, many patients declared to have diminished or ceased completely. Objective parameters were endoscopic explorations before beginning of the treatment, i.e. gastroscopy and biopsy, examinations by gastro-camera and in some cases chromography to exclude a possible malignancy. The control examinations were performed almost exclusively by gastro-camera, and that after 2 and 4 weeks. The ulcer healing stage could be clearly defined after Ohmori and Miwa (1971), its localisation and size were also recorded. Altogether it can be said, that the preparation Caved-S, by a working-principle not as yet exactly defined in all details, effects rapid healing endoscopically provable, but that ulcers with a special localisation, e.g. in the angulus-area of the posterior wall, require a longer healing time according to expectation. Clinically relevant side effects were not observed. Thus it can be concluded that Caved-S is very suitable for the treatment of ventricular ulcers. The preparation has a spasmolytical component leading quickly to freedom from pain, and a protective component effecting a healing tendency which can be demonstrated by endoscopic methods. It must be said, however, that this protective healing-promoter factor has not yet been defined pharmacologically.", "contents": "[Therapy of ulcus ventriculi with Caved-S. Use of the gastrocamera for diagnosis and control of therapy]. 36 patients with a ventricular ulcer demonstrated by endoscopy and secured by histology, were given 2 tablets Caved-S 4 times a day for 4 weeks. Clinical parameters were subjective complaints, such as pain and heartburn, which after a relatively short time, many patients declared to have diminished or ceased completely. Objective parameters were endoscopic explorations before beginning of the treatment, i.e. gastroscopy and biopsy, examinations by gastro-camera and in some cases chromography to exclude a possible malignancy. The control examinations were performed almost exclusively by gastro-camera, and that after 2 and 4 weeks. The ulcer healing stage could be clearly defined after Ohmori and Miwa (1971), its localisation and size were also recorded. Altogether it can be said, that the preparation Caved-S, by a working-principle not as yet exactly defined in all details, effects rapid healing endoscopically provable, but that ulcers with a special localisation, e.g. in the angulus-area of the posterior wall, require a longer healing time according to expectation. Clinically relevant side effects were not observed. Thus it can be concluded that Caved-S is very suitable for the treatment of ventricular ulcers. The preparation has a spasmolytical component leading quickly to freedom from pain, and a protective component effecting a healing tendency which can be demonstrated by endoscopic methods. It must be said, however, that this protective healing-promoter factor has not yet been defined pharmacologically."} {"id": "PMID:1261960", "title": "Effects of insulin-free plasma on the charcoal-separation method for radioimmunoassay of insulin.", "content": "Radioimmunoassay of insulin in rat plasma using a popular method (Albano, Ekins, Maritz and Turner 1972) involving charcoal-separation of free and antibody-bound insulin was found to be unsatisfactory despite inclusion in standard tubes of insulin-free plasma prepared in either of two ways. Insulin-free plasma and untreated plasma had different effects on adsorption of free insulin to the charcoal. It was concluded that separation with charcoal is very sensitive to any prior treatment of the plasma. Particular care must be taken to ensure that hormone-free plasma is identical in all other respects to untreated plasma.", "contents": "Effects of insulin-free plasma on the charcoal-separation method for radioimmunoassay of insulin. Radioimmunoassay of insulin in rat plasma using a popular method (Albano, Ekins, Maritz and Turner 1972) involving charcoal-separation of free and antibody-bound insulin was found to be unsatisfactory despite inclusion in standard tubes of insulin-free plasma prepared in either of two ways. Insulin-free plasma and untreated plasma had different effects on adsorption of free insulin to the charcoal. It was concluded that separation with charcoal is very sensitive to any prior treatment of the plasma. Particular care must be taken to ensure that hormone-free plasma is identical in all other respects to untreated plasma."} {"id": "PMID:1261961", "title": "Effect of metergoline, a specific serotonin antagonist, on human growth hormone response to arginine and L-dopa.", "content": "In seven normal subjects the repeated oral administration of metergoline, a specific antiserotonin agent, has enhanced HGH response to arginine infusion. Following placebo administration, arginine-induced HGH release was slightly but not significantly reduced; similarly, in eight metergoline treated subjects, HGH response to oral L-Dopa was slightly but not significantly reduced. HGH response to i.v. L-Dopa was not modified by the drug. These results suggest that serotonin controls HGH response only in response to arginine, not to L-Dopa.", "contents": "Effect of metergoline, a specific serotonin antagonist, on human growth hormone response to arginine and L-dopa. In seven normal subjects the repeated oral administration of metergoline, a specific antiserotonin agent, has enhanced HGH response to arginine infusion. Following placebo administration, arginine-induced HGH release was slightly but not significantly reduced; similarly, in eight metergoline treated subjects, HGH response to oral L-Dopa was slightly but not significantly reduced. HGH response to i.v. L-Dopa was not modified by the drug. These results suggest that serotonin controls HGH response only in response to arginine, not to L-Dopa."} {"id": "PMID:1261962", "title": "Influences of stress, age and sex on serum growth hormone and free fatty acid levels in cattle.", "content": "The serum growth hormone (BGH) and free fatty acid (FFA) concentrations of large groups of calves (male and female ranging in age from 8 to 14 days and from 3 to 6 months old), bulls, oxen, heifers and cows under normal conditions were compared with the serum BGH and FFA values of corresponding large groups of animals under stress conditions. Stress was caused by transport, as it routinely occurs, and was further reinforced by a stay of several hours in unfamiliar surroundings. Stress provokes a significant increase in serum FFA in all groups and induced a significant decrease in serum BGH in all groups, with the exception of the non-pregnant heifers. The male and female calves which were 8 to 14 days old, had significantly higher BGH levels than the older animals. The female calves from 3 to 6 months of age, and the heifers had significantly lower BGH levels than the cows. The males had higher serum BGH values than the females, but a significant difference could be demonstrated only between the male and female calves of both age-groups. The oxen, which were 1 to 3 years old, had significantly higher BGH levels than the non-pregnant heifers of the same age. It appeared that gestation had no influence on the serum BGH and FFA levels of both heifers and cows.", "contents": "Influences of stress, age and sex on serum growth hormone and free fatty acid levels in cattle. The serum growth hormone (BGH) and free fatty acid (FFA) concentrations of large groups of calves (male and female ranging in age from 8 to 14 days and from 3 to 6 months old), bulls, oxen, heifers and cows under normal conditions were compared with the serum BGH and FFA values of corresponding large groups of animals under stress conditions. Stress was caused by transport, as it routinely occurs, and was further reinforced by a stay of several hours in unfamiliar surroundings. Stress provokes a significant increase in serum FFA in all groups and induced a significant decrease in serum BGH in all groups, with the exception of the non-pregnant heifers. The male and female calves which were 8 to 14 days old, had significantly higher BGH levels than the older animals. The female calves from 3 to 6 months of age, and the heifers had significantly lower BGH levels than the cows. The males had higher serum BGH values than the females, but a significant difference could be demonstrated only between the male and female calves of both age-groups. The oxen, which were 1 to 3 years old, had significantly higher BGH levels than the non-pregnant heifers of the same age. It appeared that gestation had no influence on the serum BGH and FFA levels of both heifers and cows."} {"id": "PMID:1261963", "title": "Effect of food deprivation and hypophysectomy on in vitro protein synthesis by membrain-bound and free hepatic ribosomes.", "content": "The protein synthetic activities of membrane-bound and free hepatic ribosomes isolated from intact rats fed ad libitum, and normal rats subjected to food restriction to match that of hypophysectomised (Hx) rats were compared to the in vitro protein synthetic capacity of hepatic ribosomes isolated from Hx rats. Hypophysectomy resulted in decreased protein synthetic ability of bound ribosomes, whether protein synthesis was directed by endogenous messenger RNA (mRNA) (p less than 0.05) or by polyuridylic acid (polyU) (p less than 0.01). In contrast, the protein synthetic activity of free hepatic ribosomes from Hx rats was reduced when protein synthesis was directed by endogenous mRNA (p less than 0.05) but, when polyU was substituted as the messenger, the protein synthetic activity of these free ribosomes was equal to that of control rats. On the other hand the effects of food restriction on hepatic ribosomal function could be clearly differentiated from the effects observed following hypophysectomy. Thus, the reduced protein synthetic activity of hepatic bound ribosomes isolated from food restricted normal rats was not demonstrable, when polyU was used to direct protein synthesis. Further, food restriction had no effect on the protein synthetic activity of free hepatic ribosomes, and this was true when protein synthesis was directed by either endogenous or artificial messenger. It is concluded that hypophysectomy reduces the protein synthetic ability of both bound and free hepatic ribosomes, and this change of ribosomal function of Hx rats cannot be attributed to their decreased food intake.", "contents": "Effect of food deprivation and hypophysectomy on in vitro protein synthesis by membrain-bound and free hepatic ribosomes. The protein synthetic activities of membrane-bound and free hepatic ribosomes isolated from intact rats fed ad libitum, and normal rats subjected to food restriction to match that of hypophysectomised (Hx) rats were compared to the in vitro protein synthetic capacity of hepatic ribosomes isolated from Hx rats. Hypophysectomy resulted in decreased protein synthetic ability of bound ribosomes, whether protein synthesis was directed by endogenous messenger RNA (mRNA) (p less than 0.05) or by polyuridylic acid (polyU) (p less than 0.01). In contrast, the protein synthetic activity of free hepatic ribosomes from Hx rats was reduced when protein synthesis was directed by endogenous mRNA (p less than 0.05) but, when polyU was substituted as the messenger, the protein synthetic activity of these free ribosomes was equal to that of control rats. On the other hand the effects of food restriction on hepatic ribosomal function could be clearly differentiated from the effects observed following hypophysectomy. Thus, the reduced protein synthetic activity of hepatic bound ribosomes isolated from food restricted normal rats was not demonstrable, when polyU was used to direct protein synthesis. Further, food restriction had no effect on the protein synthetic activity of free hepatic ribosomes, and this was true when protein synthesis was directed by either endogenous or artificial messenger. It is concluded that hypophysectomy reduces the protein synthetic ability of both bound and free hepatic ribosomes, and this change of ribosomal function of Hx rats cannot be attributed to their decreased food intake."} {"id": "PMID:1261964", "title": "Control by TSH of protein turnover in thyroid subcellular fractions.", "content": "The action of TSH on protein turnover in various subcellular fractions has been investigated in dog thyroid slices incubated in vitro. The results suggest a general inhibition by TSH of protein catabolism. Using double labeline (3/ and 14C) of the proteins, an increase of the disappearance of some labeled material from the microsomal fraction in the presence of TSH has been observed. The protein nature of this material has been established by testing its susceptibility to hydrolysis by trypsin. The fact that the microsomal pellet had to be treated by triton X 100 before hydrolysis by trypsin could occur, suggests that the material is probably enclosed in, or protected by membrane vesicles. Its high molecular weight and its ability to be immunoprecipitated by an antithyroglobulin serum suggest that the microsomal protein, the disappearance of which is stimulated by TSH, is thyroglobulin or one of its subunits. It is suggested that our results reflect the acceleration by TSH of the vectorial transfer of thyroglobulin through the membranes of the endoplasmic reticulum to the colloid space.", "contents": "Control by TSH of protein turnover in thyroid subcellular fractions. The action of TSH on protein turnover in various subcellular fractions has been investigated in dog thyroid slices incubated in vitro. The results suggest a general inhibition by TSH of protein catabolism. Using double labeline (3/ and 14C) of the proteins, an increase of the disappearance of some labeled material from the microsomal fraction in the presence of TSH has been observed. The protein nature of this material has been established by testing its susceptibility to hydrolysis by trypsin. The fact that the microsomal pellet had to be treated by triton X 100 before hydrolysis by trypsin could occur, suggests that the material is probably enclosed in, or protected by membrane vesicles. Its high molecular weight and its ability to be immunoprecipitated by an antithyroglobulin serum suggest that the microsomal protein, the disappearance of which is stimulated by TSH, is thyroglobulin or one of its subunits. It is suggested that our results reflect the acceleration by TSH of the vectorial transfer of thyroglobulin through the membranes of the endoplasmic reticulum to the colloid space."} {"id": "PMID:1261965", "title": "Effect of glucose on adrenocortical activity of newborn piglets.", "content": "Adrenocortical function was followed in newborn piglets fasted for 36 hours and in piglets given only glucose or glucoplastic amino acids during this period. The greatest increase in relative adrenal weight, blood plasma 17-hydroxycorticosteroid (17-OHCS) levels and in the production of 17-OHCS by pig adrenals in vitro as compared with suckled controls was found in fasted piglets followed by amino acid-treated animals. The latter showed no significant differences in blood glucose between the initial and final values. The administration of glucose produced a transient hyperglycemia, failed to prevent the inhibition of body growth, resulted in a reduction in liver weight similar to that seen in fasted animals, and had a marked suppressive effect on the elevation of adrenocortical function. There were no significant differences in the production of 17-OHCS by adrenals in vitro per kg body weight between the glucose-treated and suckled piglets.", "contents": "Effect of glucose on adrenocortical activity of newborn piglets. Adrenocortical function was followed in newborn piglets fasted for 36 hours and in piglets given only glucose or glucoplastic amino acids during this period. The greatest increase in relative adrenal weight, blood plasma 17-hydroxycorticosteroid (17-OHCS) levels and in the production of 17-OHCS by pig adrenals in vitro as compared with suckled controls was found in fasted piglets followed by amino acid-treated animals. The latter showed no significant differences in blood glucose between the initial and final values. The administration of glucose produced a transient hyperglycemia, failed to prevent the inhibition of body growth, resulted in a reduction in liver weight similar to that seen in fasted animals, and had a marked suppressive effect on the elevation of adrenocortical function. There were no significant differences in the production of 17-OHCS by adrenals in vitro per kg body weight between the glucose-treated and suckled piglets."} {"id": "PMID:1261975", "title": "A seven-year evaluation of a career-escalation training program for indigenous nonprofessionals.", "content": "A community mental health center in an urban ghetto offers a career-escalation program in which indigenous nonprofessional mental health workers can earn a master's degree in the behavioral sciences. The program allows them paid time off for classes and study and also pays for their tuition and course materials. An evaluation of the first seven years of the program showed that only 56 of the 91 staff members who were eligible for the program entered it, and 23 subsequently dropped out. Only three trainees earned a master's degree, although 24 were pursuing or had received an associate-in-arts degree. The author briefly discusses changes that could make the program more effective, but he believes a community mental health center is not the best setting for a career-escalation program.", "contents": "A seven-year evaluation of a career-escalation training program for indigenous nonprofessionals. A community mental health center in an urban ghetto offers a career-escalation program in which indigenous nonprofessional mental health workers can earn a master's degree in the behavioral sciences. The program allows them paid time off for classes and study and also pays for their tuition and course materials. An evaluation of the first seven years of the program showed that only 56 of the 91 staff members who were eligible for the program entered it, and 23 subsequently dropped out. Only three trainees earned a master's degree, although 24 were pursuing or had received an associate-in-arts degree. The author briefly discusses changes that could make the program more effective, but he believes a community mental health center is not the best setting for a career-escalation program."} {"id": "PMID:1261976", "title": "The impact of the community mental health movement on psychiatric practice and training.", "content": "The three basic concepts of community mental health will have profound impact on many aspects of traditional psychiatric theory and practice, the author believes, and must be taken into account in psychiatric residency programs. The catchment-area concept means that psychiatrists are obligated to provide help for far larger numbers of people, including those who have problems and attitudes psychiatrists are not accustomed to dealing with. Psychiatrists must also work in partnership with communities that demand a voice in defining and labeling problems and specifying treatment modalities. The concept of promoting health as well as treating illness means that psychiatry becomes involved with broader concerns about improving the quality of life. The third concept, that behavior has family, community, social-class, and other sociocultural determinants, has already affected psychiatric practice and education, but it continues to generate friction.", "contents": "The impact of the community mental health movement on psychiatric practice and training. The three basic concepts of community mental health will have profound impact on many aspects of traditional psychiatric theory and practice, the author believes, and must be taken into account in psychiatric residency programs. The catchment-area concept means that psychiatrists are obligated to provide help for far larger numbers of people, including those who have problems and attitudes psychiatrists are not accustomed to dealing with. Psychiatrists must also work in partnership with communities that demand a voice in defining and labeling problems and specifying treatment modalities. The concept of promoting health as well as treating illness means that psychiatry becomes involved with broader concerns about improving the quality of life. The third concept, that behavior has family, community, social-class, and other sociocultural determinants, has already affected psychiatric practice and education, but it continues to generate friction."} {"id": "PMID:1261977", "title": "Retraining hospital staff for work in community programs in California.", "content": "In 1972 the California Department of Mental Hygiene offered special courses to retrain for community work those state hospital employees who might lose their jobs when the hospitals were closed. The courses were conducted by the Centers for Training in Community Psychiatry. The author describes the development, implementation, and structure of the Los Angeles course. He also presents findings that show that while participants considered the course valuable, most opted to return to the state hospital instead of taking jobs they had been offered at community mental health centers. Participants who did take community jobs tended to be slightly younger and better educated and had fewer years of experience in state hospital service than did those who returned to the hospital.", "contents": "Retraining hospital staff for work in community programs in California. In 1972 the California Department of Mental Hygiene offered special courses to retrain for community work those state hospital employees who might lose their jobs when the hospitals were closed. The courses were conducted by the Centers for Training in Community Psychiatry. The author describes the development, implementation, and structure of the Los Angeles course. He also presents findings that show that while participants considered the course valuable, most opted to return to the state hospital instead of taking jobs they had been offered at community mental health centers. Participants who did take community jobs tended to be slightly younger and better educated and had fewer years of experience in state hospital service than did those who returned to the hospital."} {"id": "PMID:1261979", "title": "A comparative study of neurotics seen in a community mental health center and in private practice.", "content": "Differences that emerge in comparisons of persons applying for psychiatric care at a mental health center with those applying to the private sector are comfounded by marked diagnostic differences beyond obvious social class differences. To circumvent that problem and to ascertain what differences, if any, persist after diagnosis is held constant, the authors examined demographic and psychosocial characteristics of neurotics in a one-year adult applicant population, the only major diagnostic group treated in large numbers and similar proportions by the center and the private sector. Findings showed that significantly more neurotic applicants in the private sector are medical referrals, are members of intact nuclear families, and do not have previous inpatient experience.", "contents": "A comparative study of neurotics seen in a community mental health center and in private practice. Differences that emerge in comparisons of persons applying for psychiatric care at a mental health center with those applying to the private sector are comfounded by marked diagnostic differences beyond obvious social class differences. To circumvent that problem and to ascertain what differences, if any, persist after diagnosis is held constant, the authors examined demographic and psychosocial characteristics of neurotics in a one-year adult applicant population, the only major diagnostic group treated in large numbers and similar proportions by the center and the private sector. Findings showed that significantly more neurotic applicants in the private sector are medical referrals, are members of intact nuclear families, and do not have previous inpatient experience."} {"id": "PMID:1262014", "title": "Laboratory diagnosis of fungal infections.", "content": "Most hospitals do not perform mycologic examinations because laboratory personnel still believe in the \"old wives' tale\" that mycology is too difficult to do and that the fungi are too infectious to handle. This discussion presents methods suitable for use in laboratories of all sizes. It is hoped that laboratories will take the initiative in offering diagnostic mycology services routinely. Medical mycology can be both a challenge and a rewarding experience to those who choose to become involved.", "contents": "Laboratory diagnosis of fungal infections. Most hospitals do not perform mycologic examinations because laboratory personnel still believe in the \"old wives' tale\" that mycology is too difficult to do and that the fungi are too infectious to handle. This discussion presents methods suitable for use in laboratories of all sizes. It is hoped that laboratories will take the initiative in offering diagnostic mycology services routinely. Medical mycology can be both a challenge and a rewarding experience to those who choose to become involved."} {"id": "PMID:1262015", "title": "The gram positive cocci.", "content": "Recent changes in taxonomy of the gram positive cocci are discussed. Views on these changes and practical methods of differentiating the staphylococci, micrococci, streptococci, and aerococci are presented. Simplified schemes, using acceptable clinical laboratory techniques, are presented that either differentiate or categorize the pathologically important gram positive coccal species.", "contents": "The gram positive cocci. Recent changes in taxonomy of the gram positive cocci are discussed. Views on these changes and practical methods of differentiating the staphylococci, micrococci, streptococci, and aerococci are presented. Simplified schemes, using acceptable clinical laboratory techniques, are presented that either differentiate or categorize the pathologically important gram positive coccal species."} {"id": "PMID:1262016", "title": "The lung in cystic fibrosis. A quantitative study including prevalence of pathologic findings among different age groups.", "content": "The autopsies of 82 patients with cystic fibrosis were reviewed with respect to pathologic changes in the lungs and their respective prevalence among different age groups. Although bronchitis, mucopurulent plugging, and bronchopneumonia were almost universally present among children of all ages, epithelial metaplasia and bronchiectasis were rarer among infants and progressively more prevalent in older age groups. Emphysema was absent in patients under two years of age and affected 11 per cent of the patients two to six years of age and 40 per cent of the patients older than six years, but was never of a severe degree by the point count method. Pulmonary hemorrhage, although uncommon, was usually associated with prominent arterial vessels in walls of bronchiectatic airways. Quantitative assessment of bronchial glands revealed Reid indices significantly higher in patients with cystic fibrosis when compared to noncystic fibrosis patients, but there was no increase in these indices with the age of the patients. Glandular hypertrophy, predominance of mucous acini within glands, and goblet cell hyperplasia of the bronchial mucosa all suggest an explanation for the copious mucous secretion of patients with cystic fibrosis. However, it was not possible to ascertain whether these findings reflect a general exocrine defect of such patients or whether they were merely a response to chronic airway infection, even though the latter is a more plausible assumption.", "contents": "The lung in cystic fibrosis. A quantitative study including prevalence of pathologic findings among different age groups. The autopsies of 82 patients with cystic fibrosis were reviewed with respect to pathologic changes in the lungs and their respective prevalence among different age groups. Although bronchitis, mucopurulent plugging, and bronchopneumonia were almost universally present among children of all ages, epithelial metaplasia and bronchiectasis were rarer among infants and progressively more prevalent in older age groups. Emphysema was absent in patients under two years of age and affected 11 per cent of the patients two to six years of age and 40 per cent of the patients older than six years, but was never of a severe degree by the point count method. Pulmonary hemorrhage, although uncommon, was usually associated with prominent arterial vessels in walls of bronchiectatic airways. Quantitative assessment of bronchial glands revealed Reid indices significantly higher in patients with cystic fibrosis when compared to noncystic fibrosis patients, but there was no increase in these indices with the age of the patients. Glandular hypertrophy, predominance of mucous acini within glands, and goblet cell hyperplasia of the bronchial mucosa all suggest an explanation for the copious mucous secretion of patients with cystic fibrosis. However, it was not possible to ascertain whether these findings reflect a general exocrine defect of such patients or whether they were merely a response to chronic airway infection, even though the latter is a more plausible assumption."} {"id": "PMID:1262017", "title": "Particulate environmental matter as seen in lung sections.", "content": "A study of particulate environmental matter as seen in lung sections is presented. These particles are blackened and are comparable to particles seen in industrial-urban environments. From the study of histologic sections an attempt is made to determine the tissue reaction to them and their ultimate fate.", "contents": "Particulate environmental matter as seen in lung sections. A study of particulate environmental matter as seen in lung sections is presented. These particles are blackened and are comparable to particles seen in industrial-urban environments. From the study of histologic sections an attempt is made to determine the tissue reaction to them and their ultimate fate."} {"id": "PMID:1262018", "title": "Meibomian gland carcinoma: report of a case with electron microscopic findings.", "content": "Meibomian gland carcinomas compose about 1 per cent of the malignant tumors of the eyelids. They present in a characteristic fashion and are frequently mistaken for chalazia. Considerable time often elapses before a diagnosis is made. Early recognition and treatment are important because these tumors can behave in an aggressive manner. The following case report illustrates these features.", "contents": "Meibomian gland carcinoma: report of a case with electron microscopic findings. Meibomian gland carcinomas compose about 1 per cent of the malignant tumors of the eyelids. They present in a characteristic fashion and are frequently mistaken for chalazia. Considerable time often elapses before a diagnosis is made. Early recognition and treatment are important because these tumors can behave in an aggressive manner. The following case report illustrates these features."} {"id": "PMID:1262019", "title": "Isolated coccidioidomycosis of the uterus.", "content": "Coccidioidomycosis rarely involves the female genital tract. This report describes a case of coccidioidomycosis that was incidentally discovered involving the uterus of an asymptomatic 70 year old woman who had squamous carcinoma of the cervix. Reports of the few previously documented examples of coccidioidomycosis of the female genitalia are reviewed. Although the uterine lesion probably resulted from a solitary focus of dissemination from a clinically inapparent and completely resolved primary pulmonary infection, evidence is presented that it may have been a primary uterine infection.", "contents": "Isolated coccidioidomycosis of the uterus. Coccidioidomycosis rarely involves the female genital tract. This report describes a case of coccidioidomycosis that was incidentally discovered involving the uterus of an asymptomatic 70 year old woman who had squamous carcinoma of the cervix. Reports of the few previously documented examples of coccidioidomycosis of the female genitalia are reviewed. Although the uterine lesion probably resulted from a solitary focus of dissemination from a clinically inapparent and completely resolved primary pulmonary infection, evidence is presented that it may have been a primary uterine infection."} {"id": "PMID:1262020", "title": "Further delineation of the clinical picture of trisomy for the distal segment of chromosome 13: report of three cases.", "content": "Three cases of partial trisomy for the distal segment of chromosome 13 are reported. Common clinical features included normal birth weight, postnatal asphyxia, convulsions, severe psychomotor retardation, normal growth, and a distinct pattern of dysmorphias consisting of trigonocephalic head with prominent metopic suture, long and markedly curved eyelashes, a stubby nose, increased distance between nose and upper lip, high-arched palate, misshapen ears with virtually absent lobules and prominent anthelices which are curved in a sharp angle, and hemangiomata. Features present in 2 cases were microcephaly, long and narrow fingers with convex nails, and hexadactyly. Two cousins were unbalanced offspring of a large family of carriers of a 9/13 translocation, whereas the third case exhibited a 13p+ chromosome which was formed de novo. The clinical features in the 3 patients are typical of the syndrome due to partial trisomy for the distal segment of chromosome 13 which shows selected and mitigated signs of full trisomy 13.", "contents": "Further delineation of the clinical picture of trisomy for the distal segment of chromosome 13: report of three cases. Three cases of partial trisomy for the distal segment of chromosome 13 are reported. Common clinical features included normal birth weight, postnatal asphyxia, convulsions, severe psychomotor retardation, normal growth, and a distinct pattern of dysmorphias consisting of trigonocephalic head with prominent metopic suture, long and markedly curved eyelashes, a stubby nose, increased distance between nose and upper lip, high-arched palate, misshapen ears with virtually absent lobules and prominent anthelices which are curved in a sharp angle, and hemangiomata. Features present in 2 cases were microcephaly, long and narrow fingers with convex nails, and hexadactyly. Two cousins were unbalanced offspring of a large family of carriers of a 9/13 translocation, whereas the third case exhibited a 13p+ chromosome which was formed de novo. The clinical features in the 3 patients are typical of the syndrome due to partial trisomy for the distal segment of chromosome 13 which shows selected and mitigated signs of full trisomy 13."} {"id": "PMID:1262021", "title": "Partial trisomy 2q and familial translocation t(2;12)(q31;q24).", "content": "Report is given of a boy with trisomy of the distal part of the long arm of chromosome 2 (q31 leads to ter) due to a balanced 2/12 translocation in the mother: 46,XX,t(2;12) (q31;q24). Other phenotypically normal carriers of this balanced translocation are the patients sister and grandfather. The patient shows a variety of dysplastic signs mainly of the face.", "contents": "Partial trisomy 2q and familial translocation t(2;12)(q31;q24). Report is given of a boy with trisomy of the distal part of the long arm of chromosome 2 (q31 leads to ter) due to a balanced 2/12 translocation in the mother: 46,XX,t(2;12) (q31;q24). Other phenotypically normal carriers of this balanced translocation are the patients sister and grandfather. The patient shows a variety of dysplastic signs mainly of the face."} {"id": "PMID:1262023", "title": "Association of Duffy blood groups with the sickle cell trait.", "content": "Among a small group of Saudi Arabs the Duffy blood group (Fy(a-b-)) was found to be associated with the sickle cell trait more often than could be explained by random gene combination thus supporting the concept that African gene flow brought the sickle cell trait to the Arabian peninsula. Based on recent observations concerning the possible role of Fy(a-b-) as a resistance factor against vivax malaria, it is proposed that the gene combination AS FyFy is likely to be selected in areas where falciparum and vivax infections are endemic and mixed infections occur frequently.", "contents": "Association of Duffy blood groups with the sickle cell trait. Among a small group of Saudi Arabs the Duffy blood group (Fy(a-b-)) was found to be associated with the sickle cell trait more often than could be explained by random gene combination thus supporting the concept that African gene flow brought the sickle cell trait to the Arabian peninsula. Based on recent observations concerning the possible role of Fy(a-b-) as a resistance factor against vivax malaria, it is proposed that the gene combination AS FyFy is likely to be selected in areas where falciparum and vivax infections are endemic and mixed infections occur frequently."} {"id": "PMID:1262024", "title": "Epidermolysis bullosa dystrophica dominans (Pasini)-a primary structural defect of the anchoring fibrils.", "content": "In epidermolysis bullosa dystrophica dominans Pasini a structural defect of the anchoring fibrils, a structural protein of the epidermo-dermal junction, has been demonstrated by electron microscopy to be constantly present not only in involved skin but also in intact skin of nonpredilection sites of blister formation. These findings render support to the concept that in dominant disorders an abnormality in a non-enzymic structural protein is more likely than in an enzymic protein.", "contents": "Epidermolysis bullosa dystrophica dominans (Pasini)-a primary structural defect of the anchoring fibrils. In epidermolysis bullosa dystrophica dominans Pasini a structural defect of the anchoring fibrils, a structural protein of the epidermo-dermal junction, has been demonstrated by electron microscopy to be constantly present not only in involved skin but also in intact skin of nonpredilection sites of blister formation. These findings render support to the concept that in dominant disorders an abnormality in a non-enzymic structural protein is more likely than in an enzymic protein."} {"id": "PMID:1262025", "title": "[Antisocial behaviour and variations in length of Y chromosome (author's transl)].", "content": "The length of they chromosome has been measured for 50 male criminals in a psychiatric security hospital and for 50 non criminal control men. The distribution was normal for the 2 populations and there was no significant difference between the mean Y/F, Yf/Y values and the number of brightly fluorescent segments. For criminal psychopaths, there was no close correlation between the size of the Y chromosome and the psychiatric or criminal background.", "contents": "[Antisocial behaviour and variations in length of Y chromosome (author's transl)]. The length of they chromosome has been measured for 50 male criminals in a psychiatric security hospital and for 50 non criminal control men. The distribution was normal for the 2 populations and there was no significant difference between the mean Y/F, Yf/Y values and the number of brightly fluorescent segments. For criminal psychopaths, there was no close correlation between the size of the Y chromosome and the psychiatric or criminal background."} {"id": "PMID:1262026", "title": "Esterase D polymorphism: description of the \"new\" allele EsD4.", "content": "Two \"new\" phenotypes of the esterase D system, named EsD 4-1 and EsD 4-2, were observed in a father and his daughter, respectively. An additional allele EsD4 is postulated.", "contents": "Esterase D polymorphism: description of the \"new\" allele EsD4. Two \"new\" phenotypes of the esterase D system, named EsD 4-1 and EsD 4-2, were observed in a father and his daughter, respectively. An additional allele EsD4 is postulated."} {"id": "PMID:1262027", "title": "A note on suxamethonium sensitivity and serum cholinesterase variants.", "content": "Sera from 21 cases of prolonged apnoea which showed normal phenotype (UU) on the basis of dibucaine and fluoride inhibition were re-examined by replacing the substrate benzoylcholine with succinylcholine (suxamethonium). 9 samples had normal enzyme activity but low dibucaine number (DN = less than 20) indicating the atypical variant; 6 sera showed no detectable enzyme activity. The remaining 6 samples had enzyme activity and DN comparable with healthy controls. The occurence of new variants of serum cholinesterase sensitive only to succinylcholine is suggested.", "contents": "A note on suxamethonium sensitivity and serum cholinesterase variants. Sera from 21 cases of prolonged apnoea which showed normal phenotype (UU) on the basis of dibucaine and fluoride inhibition were re-examined by replacing the substrate benzoylcholine with succinylcholine (suxamethonium). 9 samples had normal enzyme activity but low dibucaine number (DN = less than 20) indicating the atypical variant; 6 sera showed no detectable enzyme activity. The remaining 6 samples had enzyme activity and DN comparable with healthy controls. The occurence of new variants of serum cholinesterase sensitive only to succinylcholine is suggested."} {"id": "PMID:1262028", "title": "Short arm deletion of an X chromosome, 46,XXp-.", "content": "A 27-year-old patient of short stature with primary amenorrhea and other slight Turner signs showed a 46,XX,del(X) (qter leads to p11:) karyotype, identified by a combination of fluorescence and giemsa-banding technique. By BUdR incorporation the deleted X chromosome was shown to be the late replicating one.", "contents": "Short arm deletion of an X chromosome, 46,XXp-. A 27-year-old patient of short stature with primary amenorrhea and other slight Turner signs showed a 46,XX,del(X) (qter leads to p11:) karyotype, identified by a combination of fluorescence and giemsa-banding technique. By BUdR incorporation the deleted X chromosome was shown to be the late replicating one."} {"id": "PMID:1262041", "title": "Human colonic adenocarcinoma cells. I. Establishment and description of a new line.", "content": "A series of human colonic epithelial cell lines have been cultured from a single patient: LS-180 the original adenocarcinoma, LS-174T a trypsinized variant, and normal colonic tissue. The malignant cells, 20 to 40, mum in diameter and oval to polygonal, exhibited characteristics of normal colonic mucosal cells, namely, abundant microvilli prominent in secretory cells, and the presence of intracytoplasmic mucin vacuoles. The cultured adenocarcinoma cells, but not normal, demonstrated neoplastic properties by producing high levels of carcinoembryonic antigen (CEA) and by the ability to be propagated in hamster cheek pouches and in immunodeprived mice. The CEA production by the newly established line LS-180 released 900 times more CEA per cell into the culture medium and bore 30 times more cell-associated material than the established line, HT-29. These cell lines may permit detection of distinctive chemical, physiological, pharmacologic, and immunologic characteristics of neoplastic colonic cells.", "contents": "Human colonic adenocarcinoma cells. I. Establishment and description of a new line. A series of human colonic epithelial cell lines have been cultured from a single patient: LS-180 the original adenocarcinoma, LS-174T a trypsinized variant, and normal colonic tissue. The malignant cells, 20 to 40, mum in diameter and oval to polygonal, exhibited characteristics of normal colonic mucosal cells, namely, abundant microvilli prominent in secretory cells, and the presence of intracytoplasmic mucin vacuoles. The cultured adenocarcinoma cells, but not normal, demonstrated neoplastic properties by producing high levels of carcinoembryonic antigen (CEA) and by the ability to be propagated in hamster cheek pouches and in immunodeprived mice. The CEA production by the newly established line LS-180 released 900 times more CEA per cell into the culture medium and bore 30 times more cell-associated material than the established line, HT-29. These cell lines may permit detection of distinctive chemical, physiological, pharmacologic, and immunologic characteristics of neoplastic colonic cells."} {"id": "PMID:1262042", "title": "Selection and characterization of Chinese hamster ovary cells resistant to the cytotoxicity of lectins.", "content": "Chinese hamster ovary (CHO) cells selected in a single step for resistance to the cytotoxicity of the lectin from red kidney beans (PHA) behave as authentic somatic cell mutants. The PHA-resistant (Phar) phenotype is stable in the absence of selection; its frequency in a sensitive-population is increased several-fold by mutagenesis; and it behaves recessively in somatic cell hybrids. The activity of a specific glycosyl transferase which transfers N-acetylglucosamine (GlcNAc) to terminal alpha-mannose residues is dramatically reduced (less than or equal to 5% of the activity detected in wild-type CHO cells) in several independent PhaR clones. These clones also exhibit (a) a decreased ability to bind [125I]-PHA; (b) a marked resistance to the cytotoxicity of wheat germ agglutinin (WGA), Ricin (RIC) and Lens culinaris agglutinin (LCA); (c) a 4- to 5-fold increased sensitivity to the cytoxocity of concanavalin A (Con A); (d) an increased ability to bind 125I-Con A; and (e) decreased surface galactose residues - all properties consistent with the specific loss of the GlcNAc transferase activity. The lectins WGA, RIC, LCA and Con A have also been used to select, in a single step, resistance closes from each of two complementary CHO auxitrophic lines. These lectin-resistant clones have been characterized by their ability to survive cytotoxic doses of PHA, Con A, WGA, RIC, or LCA, and 4-5 \"lectin-resistance\" phenotypes have been demonstrated. Complementation data is being sought by somatic cell hybridization. Preliminary results show that two phenotypically-distinct Con AR mutants are complementary in that hybrid cells formed between them exhibit wild-type sensitivity to Con A.", "contents": "Selection and characterization of Chinese hamster ovary cells resistant to the cytotoxicity of lectins. Chinese hamster ovary (CHO) cells selected in a single step for resistance to the cytotoxicity of the lectin from red kidney beans (PHA) behave as authentic somatic cell mutants. The PHA-resistant (Phar) phenotype is stable in the absence of selection; its frequency in a sensitive-population is increased several-fold by mutagenesis; and it behaves recessively in somatic cell hybrids. The activity of a specific glycosyl transferase which transfers N-acetylglucosamine (GlcNAc) to terminal alpha-mannose residues is dramatically reduced (less than or equal to 5% of the activity detected in wild-type CHO cells) in several independent PhaR clones. These clones also exhibit (a) a decreased ability to bind [125I]-PHA; (b) a marked resistance to the cytotoxicity of wheat germ agglutinin (WGA), Ricin (RIC) and Lens culinaris agglutinin (LCA); (c) a 4- to 5-fold increased sensitivity to the cytoxocity of concanavalin A (Con A); (d) an increased ability to bind 125I-Con A; and (e) decreased surface galactose residues - all properties consistent with the specific loss of the GlcNAc transferase activity. The lectins WGA, RIC, LCA and Con A have also been used to select, in a single step, resistance closes from each of two complementary CHO auxitrophic lines. These lectin-resistant clones have been characterized by their ability to survive cytotoxic doses of PHA, Con A, WGA, RIC, or LCA, and 4-5 \"lectin-resistance\" phenotypes have been demonstrated. Complementation data is being sought by somatic cell hybridization. Preliminary results show that two phenotypically-distinct Con AR mutants are complementary in that hybrid cells formed between them exhibit wild-type sensitivity to Con A."} {"id": "PMID:1262043", "title": "Hormonal mechanisms for differentiation in plant tissue culture.", "content": "Cells possess extraordinary powers to organize their molecular processes not only to maintain a cell in a given steady state but also to recognize that state during differentiation. Regulation of these organizational forces appears to be under the control of chemical factors, and a hormonal concept of regulation has evolved. Hormones have been considered to act by reacting with a specific target site. This may be part of their mode of action, 0ut i would like to suggest that a hormone enters and becomes part of a total molecular resonance system. In so doing, the entire molecular system of the cell is modified.", "contents": "Hormonal mechanisms for differentiation in plant tissue culture. Cells possess extraordinary powers to organize their molecular processes not only to maintain a cell in a given steady state but also to recognize that state during differentiation. Regulation of these organizational forces appears to be under the control of chemical factors, and a hormonal concept of regulation has evolved. Hormones have been considered to act by reacting with a specific target site. This may be part of their mode of action, 0ut i would like to suggest that a hormone enters and becomes part of a total molecular resonance system. In so doing, the entire molecular system of the cell is modified."} {"id": "PMID:1262044", "title": "Hormonal control of growth and differentiation of insect tissues cultured in vitro.", "content": "This paper reviews the effects of insect hormones on lepidopteran imaginal discs cultured in vitro. Beta-ecdysone showed that RNA and protein synthesis was required for evagination and cuticle deposition. In particular, studies with actinomycin D and cycloheximide (at nontoxic levels) showed that RNA and protein synthesis during the ecdysone-dependent period was essential for subsequent development. These findings support the hypothesis that stimulation of macromolecular synthesis is fundamental to the action of ecdysone on imaginal discs. The influence of beta-ecdysone on chitin synthesis was also examined. Beta-ecdysone stimulated uptake and incorporation of tritiated-glucosamine by cultured P.interpunctella wing discs. Addition of hexosamines to the culture medium had no influence on ecdysone-induced cuticle deposition, but inhibition of glucose-uptake by cytochalasin B prevented the formation of cuticle. The action of ecdysone on particular enzymes in the chitin pathway remains to be elucidated.timulated both evatination and cuticle deposition of wing discs of Plodia interpunctella(Hubner). However, evagination required a shorter exposure to ecdysone than did cuticle deposition. Cuticle deposition was obtained under the following conditions: (a) a 24-hour pulse of beta-ecdysone (0.5-5.0 mug/ml); (b) continuous treatment with 0.2 mug/ml beta-ecdysone; or (c) continuous treatment with 0.5 to 50.0 mug/ml beta-ecdysone in medium conditioned with larval fat body...", "contents": "Hormonal control of growth and differentiation of insect tissues cultured in vitro. This paper reviews the effects of insect hormones on lepidopteran imaginal discs cultured in vitro. Beta-ecdysone showed that RNA and protein synthesis was required for evagination and cuticle deposition. In particular, studies with actinomycin D and cycloheximide (at nontoxic levels) showed that RNA and protein synthesis during the ecdysone-dependent period was essential for subsequent development. These findings support the hypothesis that stimulation of macromolecular synthesis is fundamental to the action of ecdysone on imaginal discs. The influence of beta-ecdysone on chitin synthesis was also examined. Beta-ecdysone stimulated uptake and incorporation of tritiated-glucosamine by cultured P.interpunctella wing discs. Addition of hexosamines to the culture medium had no influence on ecdysone-induced cuticle deposition, but inhibition of glucose-uptake by cytochalasin B prevented the formation of cuticle. The action of ecdysone on particular enzymes in the chitin pathway remains to be elucidated.timulated both evatination and cuticle deposition of wing discs of Plodia interpunctella(Hubner). However, evagination required a shorter exposure to ecdysone than did cuticle deposition. Cuticle deposition was obtained under the following conditions: (a) a 24-hour pulse of beta-ecdysone (0.5-5.0 mug/ml); (b) continuous treatment with 0.2 mug/ml beta-ecdysone; or (c) continuous treatment with 0.5 to 50.0 mug/ml beta-ecdysone in medium conditioned with larval fat body..."} {"id": "PMID:1262046", "title": "Device for holding a variety of tissue culture vessels during microscopy.", "content": "A device for holding tissue culture tubes, plates and flasks has been designed for use in microscopy of cell cultures, which eliminates changing holders when using varied types or sizes of vessel.", "contents": "Device for holding a variety of tissue culture vessels during microscopy. A device for holding tissue culture tubes, plates and flasks has been designed for use in microscopy of cell cultures, which eliminates changing holders when using varied types or sizes of vessel."} {"id": "PMID:1262047", "title": "Automatic gas tank switching system for CO2 incubators.", "content": "The use and construction of an automatic gas tank switching system are described. This device monitors the gas pressure in a CO2 incubator gas system and automatically switches to a reserve tank when the main supply tank is depleted. The unit contains an alarm system that signals either loss of power or gas pressure in the supply system.", "contents": "Automatic gas tank switching system for CO2 incubators. The use and construction of an automatic gas tank switching system are described. This device monitors the gas pressure in a CO2 incubator gas system and automatically switches to a reserve tank when the main supply tank is depleted. The unit contains an alarm system that signals either loss of power or gas pressure in the supply system."} {"id": "PMID:1262050", "title": "Complement activation by interaction of polyanions and polycations.", "content": "Interactions between heparin and protamine in normal human serum previously were found to activate the primary complement pathway and deplete the early-acting complement components. In the present investigation, the role of heparin-protamine complexes, immunoglobulins, C1q and C1-INH in this interaction was studied. Heparin and protamine, like antibody and antigen, were found to combine in multiple proportions; those proportions which resulted in optimal precipitation also induced maximal C consumption. Complexes formed in serum contained C1q and IgG, but the amount of C1q was insufficient to account for the total depletion of C1 haemolytic activity, and immunoglobulins were not required for activation of complement to occur: maximal consumption was observed in immunoabsorbed hypogammaglobulinaemic sera in which IgG, IgM and IgA were undetectable (less than 5, less than 10 and less than 7 mug/ml, respectively). Purified C1q aggregated heparin-protamine complexes formed or forming in the presence or absence of serum. The ability to induce maximal C consumption was rapidly lost as heparin and protamine interacted, and complexes preformed either in serum or buffer, or supernates thereof, were relatively ineffective in complement consumption. Thus, the consumption of complement seems to occur via transient reactivity with C1,probably at the level of C1q. It seems to be limited by the ability of free heparin to potentiate the activity of C1-INH, and perhaps also by its direct effect upon the early acting C components. These experiments support the concept that complement activation by interactions between polyelectrolytes such as heparin and protamine, like interactions between the antibodies and antigens, may have a role in the initiation of inflammatory reactions by direct activation of the complement system.", "contents": "Complement activation by interaction of polyanions and polycations. Interactions between heparin and protamine in normal human serum previously were found to activate the primary complement pathway and deplete the early-acting complement components. In the present investigation, the role of heparin-protamine complexes, immunoglobulins, C1q and C1-INH in this interaction was studied. Heparin and protamine, like antibody and antigen, were found to combine in multiple proportions; those proportions which resulted in optimal precipitation also induced maximal C consumption. Complexes formed in serum contained C1q and IgG, but the amount of C1q was insufficient to account for the total depletion of C1 haemolytic activity, and immunoglobulins were not required for activation of complement to occur: maximal consumption was observed in immunoabsorbed hypogammaglobulinaemic sera in which IgG, IgM and IgA were undetectable (less than 5, less than 10 and less than 7 mug/ml, respectively). Purified C1q aggregated heparin-protamine complexes formed or forming in the presence or absence of serum. The ability to induce maximal C consumption was rapidly lost as heparin and protamine interacted, and complexes preformed either in serum or buffer, or supernates thereof, were relatively ineffective in complement consumption. Thus, the consumption of complement seems to occur via transient reactivity with C1,probably at the level of C1q. It seems to be limited by the ability of free heparin to potentiate the activity of C1-INH, and perhaps also by its direct effect upon the early acting C components. These experiments support the concept that complement activation by interactions between polyelectrolytes such as heparin and protamine, like interactions between the antibodies and antigens, may have a role in the initiation of inflammatory reactions by direct activation of the complement system."} {"id": "PMID:1262051", "title": "The mediation of tissue eosinophilia in hypersensitivity reaction. I. Isolation of two different chemotactic factors from DNP-Ascaris extract-induced skin lesion in guinea-pig.", "content": "In an active cutaneous anaphylaxis induced by DNP-ascaris extract in guinea-pig, tissue eosinophilia manifested two phases; the early and mild phase became maximal in about 6 h, while the delayed and intense phase in 18-24 h. Skin extracts from the lesions exhibited chemotactic activities for eosinophils, respectively comparable to the intensity of tissue eosinophilia in each phase; and two different chemotactic factors for eosinophils of skin extracts were separated by gel filtration on Sephadex G-100. The mediation of the early phase seemed to be associated with a thermostable factor with amolefular weight of less than 1400; this factor seemed to be related to mast cell degranulation. The mediation of the delayed phase appeared to be associated with a thermolabile factor with a molecular weight of about 70,000, probably independent of mast cell degranulation; the factor was considered to be more significant than the thermostable factor, because the delayed tissue eosinophilia was more intense than the early tissue eosinophilia.", "contents": "The mediation of tissue eosinophilia in hypersensitivity reaction. I. Isolation of two different chemotactic factors from DNP-Ascaris extract-induced skin lesion in guinea-pig. In an active cutaneous anaphylaxis induced by DNP-ascaris extract in guinea-pig, tissue eosinophilia manifested two phases; the early and mild phase became maximal in about 6 h, while the delayed and intense phase in 18-24 h. Skin extracts from the lesions exhibited chemotactic activities for eosinophils, respectively comparable to the intensity of tissue eosinophilia in each phase; and two different chemotactic factors for eosinophils of skin extracts were separated by gel filtration on Sephadex G-100. The mediation of the early phase seemed to be associated with a thermostable factor with amolefular weight of less than 1400; this factor seemed to be related to mast cell degranulation. The mediation of the delayed phase appeared to be associated with a thermolabile factor with a molecular weight of about 70,000, probably independent of mast cell degranulation; the factor was considered to be more significant than the thermostable factor, because the delayed tissue eosinophilia was more intense than the early tissue eosinophilia."} {"id": "PMID:1262052", "title": "The passive transfer of humoral immunity from sows infected with Hyostrongylus rubidus (Hassal and Stiles, 1892), the red stomach worm, to their offspring and its significance in the conferring of protective immunity.", "content": "Sows repeatedly infected with large single doses of third stage infective Hyostrongylus rubidus larvae show an anamnestic circulating agglutinin response to the parasite as detected by the passive haemagglutination reaction. At farrowing the circulating antibody level dropped, whereas the colostral agglutinating antibody level increased for a period of a few hours. The predominant class of immunoglobulin which had agglutinating activity against H. rubidus was IgG. Offspring which had suckled the infected mothers had a demonstrable agglutinin titre 4 days after birth, whereas offspring which suckled non-infected mothers had no demonstable agglutinins. On infection of the offspring, those which suckled infected mothers showed a more rapid and pronounced increase and duration of circulating agglutinins than those which had suckled noninfected mothers. The parasitic burden, as determined by the duration of egg laying and total egg output, was considerably lower for the group reared on the infected mothers. These experiments show that passively transferred agglutinating antibodies, mainly of the IgG class, were associated with protection.", "contents": "The passive transfer of humoral immunity from sows infected with Hyostrongylus rubidus (Hassal and Stiles, 1892), the red stomach worm, to their offspring and its significance in the conferring of protective immunity. Sows repeatedly infected with large single doses of third stage infective Hyostrongylus rubidus larvae show an anamnestic circulating agglutinin response to the parasite as detected by the passive haemagglutination reaction. At farrowing the circulating antibody level dropped, whereas the colostral agglutinating antibody level increased for a period of a few hours. The predominant class of immunoglobulin which had agglutinating activity against H. rubidus was IgG. Offspring which had suckled the infected mothers had a demonstrable agglutinin titre 4 days after birth, whereas offspring which suckled non-infected mothers had no demonstable agglutinins. On infection of the offspring, those which suckled infected mothers showed a more rapid and pronounced increase and duration of circulating agglutinins than those which had suckled noninfected mothers. The parasitic burden, as determined by the duration of egg laying and total egg output, was considerably lower for the group reared on the infected mothers. These experiments show that passively transferred agglutinating antibodies, mainly of the IgG class, were associated with protection."} {"id": "PMID:1262053", "title": "Recongnition by guinea-pig peritoneal exudate cells of conformationally different states of the collagen molecule.", "content": "Guinea-pig peritoneal exudate cells were tested in vitro in the presence or absence of specific antiserum to native collagen for their capacity to discriminate between native and denatured collagens of various species. Adherent exudate cells bound denatured collagens, regardless of the origin of the collagen or the presence of serum. The binding was reduced if the cells were pretreated with trypsin. Recovery of binding was mediated by a normal serum component resembling an IgM antibody to denatured collagen. In the presence of normal serum, native collagen was only marginally bound, apparently in a non-specific manner. Uptake of native heterologous collagens was greatly increased in the presence of specific antiserum to native collagen with specificity of binding reflecting the type of collagen. Binding of denatured and native collagen occur via independent mechanisms.", "contents": "Recongnition by guinea-pig peritoneal exudate cells of conformationally different states of the collagen molecule. Guinea-pig peritoneal exudate cells were tested in vitro in the presence or absence of specific antiserum to native collagen for their capacity to discriminate between native and denatured collagens of various species. Adherent exudate cells bound denatured collagens, regardless of the origin of the collagen or the presence of serum. The binding was reduced if the cells were pretreated with trypsin. Recovery of binding was mediated by a normal serum component resembling an IgM antibody to denatured collagen. In the presence of normal serum, native collagen was only marginally bound, apparently in a non-specific manner. Uptake of native heterologous collagens was greatly increased in the presence of specific antiserum to native collagen with specificity of binding reflecting the type of collagen. Binding of denatured and native collagen occur via independent mechanisms."} {"id": "PMID:1262054", "title": "In vitro uptake and digestion of immune complexes containing guinea-pig IgG1 and IgG2 antibodies by macrophages.", "content": "The uptake and digestion of immune complexes by peritoneal macrophages from oil-stimulated guinea-pigs were studied using 125I-labelled guinea-pig IgG1 and IgG2 antibodies to hen ovalbumin. When the IgG1 or IgG2 antibody was incubated with homologous antigen at antigen-antibody ratios ranging from 0-01 to 10, the complexes produced were preferentially taken up by macrophages in the absence of complement and digestion by intracellular enzymes. The uptake and digestion of complexes reached a maximum at an antigen-antibody ratio of 0-1-0-5. In this respect, the IgG1 antibody was indistinguishable from the IgG2 antibody having a cytophilic activity. These observations suggest that some conformational changes in both the IgG1 and IgG2 antibodies or specific molecular arrangement in the lattice work of both the complexes may increase the strength of binding of complexes to macrophages, independently of the difference in biological activities between these two antibodies.", "contents": "In vitro uptake and digestion of immune complexes containing guinea-pig IgG1 and IgG2 antibodies by macrophages. The uptake and digestion of immune complexes by peritoneal macrophages from oil-stimulated guinea-pigs were studied using 125I-labelled guinea-pig IgG1 and IgG2 antibodies to hen ovalbumin. When the IgG1 or IgG2 antibody was incubated with homologous antigen at antigen-antibody ratios ranging from 0-01 to 10, the complexes produced were preferentially taken up by macrophages in the absence of complement and digestion by intracellular enzymes. The uptake and digestion of complexes reached a maximum at an antigen-antibody ratio of 0-1-0-5. In this respect, the IgG1 antibody was indistinguishable from the IgG2 antibody having a cytophilic activity. These observations suggest that some conformational changes in both the IgG1 and IgG2 antibodies or specific molecular arrangement in the lattice work of both the complexes may increase the strength of binding of complexes to macrophages, independently of the difference in biological activities between these two antibodies."} {"id": "PMID:1262055", "title": "Properties of a mutant of Streptococcus mutans altered in glucosyltransferase activity.", "content": "A mutant of Streptococcus mutans GS-5 has been isolated as a smooth colonial variant on mitis salivarius agar. This mutant, designated SNG-1, adheres to glass surfaces as well as the parental organism when grown in the presence of sucrose. However, in contrast to the parental organism, glucose-grown cultures of the mutant did not adhere to smooth surfaces when incubated with sucrose under nongrowing conditions. The inability of the mutant organism to adhere to glass surfaces under the latter condition was a result to markedly reduced levels of mutant cell-associated glucosyltransferase activity. In addition, the extracellular activity of the mutant was also severely depressed relative to the parental activity. The reduced levels of mutant enzyme activity appear to be a result of a mutation in a structural gene coding for glucosyltransferase activity since (i) mutant glucosyltransferase activity is much less resistant to heat inactivation compared to the parental enzymes and (ii) the migration patterns of the mutant and parental enzymes differ on polyacrylamide gels and after isoelectric focusing on polyacrylamide gels. However, the kinetic properties of the mutant enzymes are similar to those of the comparable parental activities in terms of pH and temperature optima and Km values for sucrose. The mutant enzyme responsible for soluble glucan synthesis has been purified approximately 300-fold. These results are discussed in terms of the mechanism of glucan synthesis by S. mutans.", "contents": "Properties of a mutant of Streptococcus mutans altered in glucosyltransferase activity. A mutant of Streptococcus mutans GS-5 has been isolated as a smooth colonial variant on mitis salivarius agar. This mutant, designated SNG-1, adheres to glass surfaces as well as the parental organism when grown in the presence of sucrose. However, in contrast to the parental organism, glucose-grown cultures of the mutant did not adhere to smooth surfaces when incubated with sucrose under nongrowing conditions. The inability of the mutant organism to adhere to glass surfaces under the latter condition was a result to markedly reduced levels of mutant cell-associated glucosyltransferase activity. In addition, the extracellular activity of the mutant was also severely depressed relative to the parental activity. The reduced levels of mutant enzyme activity appear to be a result of a mutation in a structural gene coding for glucosyltransferase activity since (i) mutant glucosyltransferase activity is much less resistant to heat inactivation compared to the parental enzymes and (ii) the migration patterns of the mutant and parental enzymes differ on polyacrylamide gels and after isoelectric focusing on polyacrylamide gels. However, the kinetic properties of the mutant enzymes are similar to those of the comparable parental activities in terms of pH and temperature optima and Km values for sucrose. The mutant enzyme responsible for soluble glucan synthesis has been purified approximately 300-fold. These results are discussed in terms of the mechanism of glucan synthesis by S. mutans."} {"id": "PMID:1262056", "title": "Streptococcus mutans dextransucrase: mode of interaction with high-molecular-weight dextran and role in cellular aggregation.", "content": "The interaction between Streptococcus mutans dextransucrase (EC 2.4.1.5) and high-molecular-weight dextran was studied in both the presence and absence of substrate sucrose. Equivalent weight-percent solutions of primer dextrans that differed 200-fold in molecular weight were found to be equally efficient in priming new dextran synthesis. Sodium borohydride reduction of dextran had no effect on its priming ability. These results suggest that dextran synthesis proceeds by addition of glucosyl residues to nonreducing termini of primer dextrans and that several enzyme molecules simultaneously bind to single high-molecular-weight dextran molecules. Kinetic data suggested that dextransucrase contains only one dextran binding site per enzyme molecule. The nature of the commonly observed highly aggregated state of dextransucrase was also studied. Two types of enzyme aggregates were distinguished: (i) oligomeric enzyme aggregates that formed in the absence of dextran and were dissociated by 1 M KCl; and (ii) dextran-induced enzyme aggregates that were stable to 3 M salt. Oligomeric enzyme aggregates were obtained from supernatants of fructose-grown cultures, whereas dextran-induced enzyme aggregates appeared to be present in glucose-grown cultures. The molecular weight of the smallest species of dextran-free detransucrase observed in solutions of 1 M KCl was estimated to be 40,000 by gel column chromatography. Addition of dextran to primer-dependent dextransucrase resulted in formation of complexes that were stable in CsCl density gradients and exhibited a buoyant density of 1.382 g/cm3 as compared with a buoyant density of 1.302 g/cm3 exhibited by dextransucrase. The enzyme-dextran complexes observed in CsCl density gradients contained about 25% dextran. This corresponded to 150 enzyme molecules (molecular weight, 40,000) per dextran molecule (molecular weight, 2 X 10(6)). The implication of these results to the mechanism of sucrose- and dextran-induced aggregation of S. mutans is discussed.", "contents": "Streptococcus mutans dextransucrase: mode of interaction with high-molecular-weight dextran and role in cellular aggregation. The interaction between Streptococcus mutans dextransucrase (EC 2.4.1.5) and high-molecular-weight dextran was studied in both the presence and absence of substrate sucrose. Equivalent weight-percent solutions of primer dextrans that differed 200-fold in molecular weight were found to be equally efficient in priming new dextran synthesis. Sodium borohydride reduction of dextran had no effect on its priming ability. These results suggest that dextran synthesis proceeds by addition of glucosyl residues to nonreducing termini of primer dextrans and that several enzyme molecules simultaneously bind to single high-molecular-weight dextran molecules. Kinetic data suggested that dextransucrase contains only one dextran binding site per enzyme molecule. The nature of the commonly observed highly aggregated state of dextransucrase was also studied. Two types of enzyme aggregates were distinguished: (i) oligomeric enzyme aggregates that formed in the absence of dextran and were dissociated by 1 M KCl; and (ii) dextran-induced enzyme aggregates that were stable to 3 M salt. Oligomeric enzyme aggregates were obtained from supernatants of fructose-grown cultures, whereas dextran-induced enzyme aggregates appeared to be present in glucose-grown cultures. The molecular weight of the smallest species of dextran-free detransucrase observed in solutions of 1 M KCl was estimated to be 40,000 by gel column chromatography. Addition of dextran to primer-dependent dextransucrase resulted in formation of complexes that were stable in CsCl density gradients and exhibited a buoyant density of 1.382 g/cm3 as compared with a buoyant density of 1.302 g/cm3 exhibited by dextransucrase. The enzyme-dextran complexes observed in CsCl density gradients contained about 25% dextran. This corresponded to 150 enzyme molecules (molecular weight, 40,000) per dextran molecule (molecular weight, 2 X 10(6)). The implication of these results to the mechanism of sucrose- and dextran-induced aggregation of S. mutans is discussed."} {"id": "PMID:1262057", "title": "Comparison of subcutaneous and intraperitoneal staphylococcal infections in normal and complement-deficient mice.", "content": "From a comparison of the effects produced by injecting different strains of Staphylococcus aureus either subcutaneously or intraperitoneally into normal, complement-deficient, or complement-depleted mice, it was possible to assess the pathogenic significance of various staphylococcal virulence factors and the defensive role of complement components in the two sites of infection. In skin lesions the inflammation-suppressing factor found in the cell walls of strain PS80 played a major role. In contrast, in intraperitoneal infection the antiphagocytic capsule of the Smith diffuse and M strains was more important. All strains used produced alpha-hemolysin, which is the ultimate lethal agent in intraperitoneal infection but is only one factor in the production of dermonecrosis. The severity of the skin lesions was inversely related to the amount of early fluid exudate rather than to the rate of bacterial growth, whereas in the peritoneum increased bacterial growth was associated with increased mortality. Both C3 and C5 were needed in the production of fluid exudate in response to staphylococcal skin infection. C3 appeared to be more important in the increased exudate formed in immune mice. In the peritoneum the opsonic and chemotactic actions for complement were important as shown by the results in cobra venom-treated normal mice and in C5-deficient B10D2 old-line mice.", "contents": "Comparison of subcutaneous and intraperitoneal staphylococcal infections in normal and complement-deficient mice. From a comparison of the effects produced by injecting different strains of Staphylococcus aureus either subcutaneously or intraperitoneally into normal, complement-deficient, or complement-depleted mice, it was possible to assess the pathogenic significance of various staphylococcal virulence factors and the defensive role of complement components in the two sites of infection. In skin lesions the inflammation-suppressing factor found in the cell walls of strain PS80 played a major role. In contrast, in intraperitoneal infection the antiphagocytic capsule of the Smith diffuse and M strains was more important. All strains used produced alpha-hemolysin, which is the ultimate lethal agent in intraperitoneal infection but is only one factor in the production of dermonecrosis. The severity of the skin lesions was inversely related to the amount of early fluid exudate rather than to the rate of bacterial growth, whereas in the peritoneum increased bacterial growth was associated with increased mortality. Both C3 and C5 were needed in the production of fluid exudate in response to staphylococcal skin infection. C3 appeared to be more important in the increased exudate formed in immune mice. In the peritoneum the opsonic and chemotactic actions for complement were important as shown by the results in cobra venom-treated normal mice and in C5-deficient B10D2 old-line mice."} {"id": "PMID:1262058", "title": "Comparison of mouse strain skin sensitivities to anaphylactic mediators and susceptibility to passive cutaneous anaphylactic reactions.", "content": "CFW, ICR, and C57Bl/6J mouse strains were examined and compared for their levels of skin sensitivity to histamine and mellitin (a potent mast cell degranulator) and for their susceptibilities to immunoglobulin E-induced passive cutaneous anaphylactic (PCA) reactions. ICR mice were found to exhibit the highest level of sensitivity to histamine and mellitin, whereas C57Bl/6J exhibited the least. CFW mice proved to be the best PCA recipients, whereas ICR mice were the poorest. On the basis of this evidence, no direct correlation is indicated between level of sensitivity to anaphylactic mediators and degree of susceptibility to immunoglobulin E-induced PCA reactions.", "contents": "Comparison of mouse strain skin sensitivities to anaphylactic mediators and susceptibility to passive cutaneous anaphylactic reactions. CFW, ICR, and C57Bl/6J mouse strains were examined and compared for their levels of skin sensitivity to histamine and mellitin (a potent mast cell degranulator) and for their susceptibilities to immunoglobulin E-induced passive cutaneous anaphylactic (PCA) reactions. ICR mice were found to exhibit the highest level of sensitivity to histamine and mellitin, whereas C57Bl/6J exhibited the least. CFW mice proved to be the best PCA recipients, whereas ICR mice were the poorest. On the basis of this evidence, no direct correlation is indicated between level of sensitivity to anaphylactic mediators and degree of susceptibility to immunoglobulin E-induced PCA reactions."} {"id": "PMID:1262059", "title": "Influenza infection in ferrets: role of serum antibody in protection and recovery.", "content": "The passive administration of ferret antiserum to Ao (H0N1) influenza virus failed to protect the recipient ferrets from subsequent infection with homologous virus. This susceptibility to infection was observed even when the passively acquired serum hemagglutination inhibition (HI) titer was similar to peak convalescent titers. It is therefore concluded that serum antibody alone is probably not a major factor in the prevention of influenza infection. This does not rule out a possible role for serum antibody in prevention of illness. Subsequent to infection, ferrets that had received passive antisera failed to develop high levels of serum HI antibody. In fact, many had no detectable serum antibody (less than 1:8). These animals shed virus for periods of time quite similar to those of infected control animals, which did develope serum antibody. From these data it was concluded that detectable serum HI antibody does not play a significant role in the recovery of ferrets from influenza infection. Interferon was present in high concentrations in the secretions a few days prior to cessation of virus shedding, but it is not clear whether this was the cause of the recovery or merely a concomitant event. Twenty-one days after initial infection two-thirds of the ferrets that had received passive antibody and all control animals were immune to reinfection with the homologous influenza virus. Since the former group had little or no detectable serum HI antibody but most members were immune, there must be some other host mechanism to account for the immunity.", "contents": "Influenza infection in ferrets: role of serum antibody in protection and recovery. The passive administration of ferret antiserum to Ao (H0N1) influenza virus failed to protect the recipient ferrets from subsequent infection with homologous virus. This susceptibility to infection was observed even when the passively acquired serum hemagglutination inhibition (HI) titer was similar to peak convalescent titers. It is therefore concluded that serum antibody alone is probably not a major factor in the prevention of influenza infection. This does not rule out a possible role for serum antibody in prevention of illness. Subsequent to infection, ferrets that had received passive antisera failed to develop high levels of serum HI antibody. In fact, many had no detectable serum antibody (less than 1:8). These animals shed virus for periods of time quite similar to those of infected control animals, which did develope serum antibody. From these data it was concluded that detectable serum HI antibody does not play a significant role in the recovery of ferrets from influenza infection. Interferon was present in high concentrations in the secretions a few days prior to cessation of virus shedding, but it is not clear whether this was the cause of the recovery or merely a concomitant event. Twenty-one days after initial infection two-thirds of the ferrets that had received passive antibody and all control animals were immune to reinfection with the homologous influenza virus. Since the former group had little or no detectable serum HI antibody but most members were immune, there must be some other host mechanism to account for the immunity."} {"id": "PMID:1262060", "title": "Influenza virus population dynamics in the respiratory tract of experimentally infected mice.", "content": "Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar challenge. In all of the infections, the highest virus concentrations were observed in the lungs. Peak concentrations in the trachea were lower than in the lungs but higher than in the nasopharynx. Decreasing virus levels were observed by 120 h after challenge and were generally below detectable levels by the end of 10 days. A compartmental model of a single mathematical form was developed which provided close fits of the virus concentration measurements regardless of the challenge dose, site of initial deposition, or respiratory tissue considered. The model includes seven compartments with five associated rate parameters. The application of compartmental modeling techniques and expression of the virus population dynamics in mathematical terms is regarded as a new approach to the study of the pathogenesis of infections.", "contents": "Influenza virus population dynamics in the respiratory tract of experimentally infected mice. Virus population dynamics in the lungs, trachea, and nasopharynx of Swiss-ICR mice were studied after respiratory challenge with mouse-adapted preparations of strain A2/Aichi/2/68 influenza virus. Markedly higher doses of virus were required to produce infection with nasopharyngeal challenge than with bronchoalveolar challenge. In all of the infections, the highest virus concentrations were observed in the lungs. Peak concentrations in the trachea were lower than in the lungs but higher than in the nasopharynx. Decreasing virus levels were observed by 120 h after challenge and were generally below detectable levels by the end of 10 days. A compartmental model of a single mathematical form was developed which provided close fits of the virus concentration measurements regardless of the challenge dose, site of initial deposition, or respiratory tissue considered. The model includes seven compartments with five associated rate parameters. The application of compartmental modeling techniques and expression of the virus population dynamics in mathematical terms is regarded as a new approach to the study of the pathogenesis of infections."} {"id": "PMID:1262061", "title": "Virulence factors involved in the intraperitoneal infection of adult mice with Vibrio cholerae.", "content": "Nonmotile mutants of Vibrio cholerae isolated from Ogawa, Inaba, and El Tor strains were less virulent than parent wild types when administered to adult mice intraperitoneally. The cells were suspended in 5% hog gastric mucin. Antitoxic immunity did not protect mice against this type of challenge, but a ribosomally derived vaccine did. Intraperitoneal injection of 10 50% lethal doses of enterotoxin (based on intravenous doses) was without toxic manifestations as were 10(10) heat-killed vibrios similarly administered, regardless of strain. Virulent organisms killed with formalin or ultraviolet irradiation were significantly lethal at a dose of 10(10) cells. Mice made tolerant to endotoxin were protected from death caused by an injection of 3 X 10(10) boiled cells, but they did not survive an injection of formalin-killed cells. It is believed that the cause of death in this animal model of cholera is dependent, at least in part, on a toxic heat-labile moiety closely associated with the vibrios.", "contents": "Virulence factors involved in the intraperitoneal infection of adult mice with Vibrio cholerae. Nonmotile mutants of Vibrio cholerae isolated from Ogawa, Inaba, and El Tor strains were less virulent than parent wild types when administered to adult mice intraperitoneally. The cells were suspended in 5% hog gastric mucin. Antitoxic immunity did not protect mice against this type of challenge, but a ribosomally derived vaccine did. Intraperitoneal injection of 10 50% lethal doses of enterotoxin (based on intravenous doses) was without toxic manifestations as were 10(10) heat-killed vibrios similarly administered, regardless of strain. Virulent organisms killed with formalin or ultraviolet irradiation were significantly lethal at a dose of 10(10) cells. Mice made tolerant to endotoxin were protected from death caused by an injection of 3 X 10(10) boiled cells, but they did not survive an injection of formalin-killed cells. It is believed that the cause of death in this animal model of cholera is dependent, at least in part, on a toxic heat-labile moiety closely associated with the vibrios."} {"id": "PMID:1262062", "title": "Characterization of an anti-glucosyltransferase serum specific for insoluble glucan synthesis by Streptococcus mutans.", "content": "An anti-glucosyltransferase serum, which synthesized 96% insoluble glucans, was prepared against a purified enzyme preparation from Streptococcus mutans strain HS6 (serotype a). This serum was examined for its effects on glucan synthesis by crude enzyme preparations from eight strains (four serotypes) of S. mutans and for the ability of these preparations to promote adherence of S. mutans to a smooth surface. Glucosyltransferase activity was assayed by measuring the incorporation of glucose from [14C]glucose-labeled sucrose into water-insoluble and water-soluble (ethanol-insoluble) glucans. Anti-glucosyltransferase serum inhibited insoluble glucan synthesis by crude enzyme preparations from cells of the four serotypes of S. mutans. Enzymes from strains of types a, b, and d were inhibited between 70 to 90%; enzymes from type c strains were inhibited from 45 to 60%. The adherence to a glass surface of heat-killed cells from these four serotypes was likewise inhibited. Soluble glucan synthesis was not inhibited by the serum, and in some cases its synthesis increased as insoluble glucan synthesis decreased.", "contents": "Characterization of an anti-glucosyltransferase serum specific for insoluble glucan synthesis by Streptococcus mutans. An anti-glucosyltransferase serum, which synthesized 96% insoluble glucans, was prepared against a purified enzyme preparation from Streptococcus mutans strain HS6 (serotype a). This serum was examined for its effects on glucan synthesis by crude enzyme preparations from eight strains (four serotypes) of S. mutans and for the ability of these preparations to promote adherence of S. mutans to a smooth surface. Glucosyltransferase activity was assayed by measuring the incorporation of glucose from [14C]glucose-labeled sucrose into water-insoluble and water-soluble (ethanol-insoluble) glucans. Anti-glucosyltransferase serum inhibited insoluble glucan synthesis by crude enzyme preparations from cells of the four serotypes of S. mutans. Enzymes from strains of types a, b, and d were inhibited between 70 to 90%; enzymes from type c strains were inhibited from 45 to 60%. The adherence to a glass surface of heat-killed cells from these four serotypes was likewise inhibited. Soluble glucan synthesis was not inhibited by the serum, and in some cases its synthesis increased as insoluble glucan synthesis decreased."} {"id": "PMID:1262063", "title": "Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California.", "content": "Various clinical, virological, immunological, and morphological aspects of velogenic Newcastle disease were defined in chickens inoculated by natural routes with the Missouri-(H) Len 1950 strain. The disease initially appeared as a severe pneumonitis from which most birds recovered. Several days later, many of these birds developed severe encephalitic signs, largely referable to inflammatory changes in the cerebellum. During the pneumonic stage, virus was easily isolated in relatively high titers from the brains of all chickens, and viral products were easily detected in Purkinje neurons. However, when the encephalitis developed, virus was isolated irregularly and in low titers from brains, and morphological evidence for the presence of viral products could not longer be obtained. The encephalitic disease is discussed in relation to encephalitic syndromes induced by other neurotrophic viruses.", "contents": "Reed Neurological Research Center, UCLA School of Medicine, Los Angeles, California. Various clinical, virological, immunological, and morphological aspects of velogenic Newcastle disease were defined in chickens inoculated by natural routes with the Missouri-(H) Len 1950 strain. The disease initially appeared as a severe pneumonitis from which most birds recovered. Several days later, many of these birds developed severe encephalitic signs, largely referable to inflammatory changes in the cerebellum. During the pneumonic stage, virus was easily isolated in relatively high titers from the brains of all chickens, and viral products were easily detected in Purkinje neurons. However, when the encephalitis developed, virus was isolated irregularly and in low titers from brains, and morphological evidence for the presence of viral products could not longer be obtained. The encephalitic disease is discussed in relation to encephalitic syndromes induced by other neurotrophic viruses."} {"id": "PMID:1262064", "title": "Variability of the immunological state of germfree colostrum-deprived Minnesota miniature piglets.", "content": "Minnesota miniature piglets obtained by hysterectomy and deprived of colostrum were examined for the presence of immunoglobulin by immunoelectrophoresis, double-gel diffusion, and radial immunodiffusion techniques with specific anti-immunoglobulin chain sera. A large amount of variability existed between different litters of piglets and between different piglets within the same litter, ranging from no detectable immunoglobulin in the serum to very high immunoglobulin levels approaching that of the adult pig. All known classes of porcine immunoglobulin including immunoglobulin G, immunoglobulin M, and immunoglobulin A could be found in the sera from litters where there was extensive placental damage. This contaminating immunoglobulin was shown to have antibody activity to actinophage MSP-2 even when present in very low concentrations. The low level contamination with immunoglobulin G, which was the most frequently encountered type of contaminant, was demonstrated to be similar to sow immunoglobulin G both antigenically and in its molecular size. The data demonstrates that individual piglets must be tested for immunoglobulin content rather than being assumed to be immunologically \"virgin\" and emphasizes the need for an intact placenta barrier to obtain piglets free from maternal immunoglobulin and devoid of antigenic stimulation.", "contents": "Variability of the immunological state of germfree colostrum-deprived Minnesota miniature piglets. Minnesota miniature piglets obtained by hysterectomy and deprived of colostrum were examined for the presence of immunoglobulin by immunoelectrophoresis, double-gel diffusion, and radial immunodiffusion techniques with specific anti-immunoglobulin chain sera. A large amount of variability existed between different litters of piglets and between different piglets within the same litter, ranging from no detectable immunoglobulin in the serum to very high immunoglobulin levels approaching that of the adult pig. All known classes of porcine immunoglobulin including immunoglobulin G, immunoglobulin M, and immunoglobulin A could be found in the sera from litters where there was extensive placental damage. This contaminating immunoglobulin was shown to have antibody activity to actinophage MSP-2 even when present in very low concentrations. The low level contamination with immunoglobulin G, which was the most frequently encountered type of contaminant, was demonstrated to be similar to sow immunoglobulin G both antigenically and in its molecular size. The data demonstrates that individual piglets must be tested for immunoglobulin content rather than being assumed to be immunologically \"virgin\" and emphasizes the need for an intact placenta barrier to obtain piglets free from maternal immunoglobulin and devoid of antigenic stimulation."} {"id": "PMID:1262065", "title": "Purification and characterization of a staphylococcal epidermolytic toxin.", "content": "A staphylococcal exotoxin that causes epidermolysis when injected into the skin of the newborn mouse and man was highly purified by coventional biochemical techniques. With Staphylococcus aureus EV, the epidermolytic toxin was a major protein component of supernatant culture fluids. The initial step in purification was zone electrophoresis in Pevikon carried out at pH 9.0, the isoelectric point of alpha-hemolytic toxin, which remained near the origin. Fractions containing the epidermolytic toxin, but free of alpha-toxin, were then subjected to cation exchange chromatography on carboxymethyl-Sephadex C-50 to remove trace contaminants. A major highly purified epidermolytic toxin migrated as a single band in polyacrylamide gel electrophoresis, sedimented as a single component in the analytical ultracentrifuge, and elicited a single precipitating antibody after injection into rabbits. A smaller amount of a second epidermolytic toxin, identical in molecular weight and antigenicity but differing in electrophoretic behavior from the major molecular species, was also identified. The epidermolytic factor had a molecular weight of 28,600 +/- 400 by sodium dodecyl sulfate-acrylamide electrophoresis and 32,500 +/- 120 by approach to sedimentation equilibrium.", "contents": "Purification and characterization of a staphylococcal epidermolytic toxin. A staphylococcal exotoxin that causes epidermolysis when injected into the skin of the newborn mouse and man was highly purified by coventional biochemical techniques. With Staphylococcus aureus EV, the epidermolytic toxin was a major protein component of supernatant culture fluids. The initial step in purification was zone electrophoresis in Pevikon carried out at pH 9.0, the isoelectric point of alpha-hemolytic toxin, which remained near the origin. Fractions containing the epidermolytic toxin, but free of alpha-toxin, were then subjected to cation exchange chromatography on carboxymethyl-Sephadex C-50 to remove trace contaminants. A major highly purified epidermolytic toxin migrated as a single band in polyacrylamide gel electrophoresis, sedimented as a single component in the analytical ultracentrifuge, and elicited a single precipitating antibody after injection into rabbits. A smaller amount of a second epidermolytic toxin, identical in molecular weight and antigenicity but differing in electrophoretic behavior from the major molecular species, was also identified. The epidermolytic factor had a molecular weight of 28,600 +/- 400 by sodium dodecyl sulfate-acrylamide electrophoresis and 32,500 +/- 120 by approach to sedimentation equilibrium."} {"id": "PMID:1262088", "title": "Social-psychological correlates of drug use among Colombian university students.", "content": "This paper reports the results of a large-scale study conducted among Colombian college students directed at finding patterns of use of legal and illegal drugs. The subjects reported reasons for use and nonuse of the different substances, use on the part of parents, parent's attitudes toward use, effects, attitudes toward drug use, and a series of sociodemographic variables. The results were later analyzed in relation to social learning variables that could differentiate marijuana users and nonusers. Results are also reported on personality differences between users and nonusers as measured by the Maudsley Personality Inventory.", "contents": "Social-psychological correlates of drug use among Colombian university students. This paper reports the results of a large-scale study conducted among Colombian college students directed at finding patterns of use of legal and illegal drugs. The subjects reported reasons for use and nonuse of the different substances, use on the part of parents, parent's attitudes toward use, effects, attitudes toward drug use, and a series of sociodemographic variables. The results were later analyzed in relation to social learning variables that could differentiate marijuana users and nonusers. Results are also reported on personality differences between users and nonusers as measured by the Maudsley Personality Inventory."} {"id": "PMID:1262089", "title": "Drug use among white and American Indian high school youth.", "content": "Data are presented on a sample of white (N = 391) and American Indian (N = 120) high school youth attending the four high schools in the vicinity of Wyoming's Wind River Reservation. For the most part, the Indian youth were members of either the Arapahoe or Shoshone tribes. The general null hypothesis that no significant differences existed between white and Indian youth in either attitudes toward drug use or in the use of drugs was rejected. The data indicate that Indian youth have a more favorable attitude toward the use of marijuana and other drugs than do white youth. Indian youth were also more likely than white youth to try using marijuana and other drugs, but no more likely than whites to continue using such drugs after having tried them.", "contents": "Drug use among white and American Indian high school youth. Data are presented on a sample of white (N = 391) and American Indian (N = 120) high school youth attending the four high schools in the vicinity of Wyoming's Wind River Reservation. For the most part, the Indian youth were members of either the Arapahoe or Shoshone tribes. The general null hypothesis that no significant differences existed between white and Indian youth in either attitudes toward drug use or in the use of drugs was rejected. The data indicate that Indian youth have a more favorable attitude toward the use of marijuana and other drugs than do white youth. Indian youth were also more likely than white youth to try using marijuana and other drugs, but no more likely than whites to continue using such drugs after having tried them."} {"id": "PMID:1262090", "title": "Recent trends in the demography of heroin addiction among youthful offenders.", "content": "Trends in demographic characteristics associated with heroin addiction in successive cohorts of a young offender population over the 5-year period 1968-1972 were examined within the framework of two contradictory views of the social competence of the addict provided by the literature. In general, heroin addicts during this period were found to be older, better educated, and more intelligent than nonaddicts. In addition, the racial composition of both the addict and nonaddict samples became increasingly non-White in composition and better educated; nonaddicts became increasingly older; and no significant trends with respect to intelligence took place. These findings support the view of the addict as being relatively more socially competent than his nonaddict offender peer. Implications of these findings for a model of addiction and rehabilitation are discussed.", "contents": "Recent trends in the demography of heroin addiction among youthful offenders. Trends in demographic characteristics associated with heroin addiction in successive cohorts of a young offender population over the 5-year period 1968-1972 were examined within the framework of two contradictory views of the social competence of the addict provided by the literature. In general, heroin addicts during this period were found to be older, better educated, and more intelligent than nonaddicts. In addition, the racial composition of both the addict and nonaddict samples became increasingly non-White in composition and better educated; nonaddicts became increasingly older; and no significant trends with respect to intelligence took place. These findings support the view of the addict as being relatively more socially competent than his nonaddict offender peer. Implications of these findings for a model of addiction and rehabilitation are discussed."} {"id": "PMID:1262091", "title": "Methaqualone (Mandrax) abuse, urine testing, and identification: clinical correlation between a new mass urinalysis test and a military drug abuse program.", "content": "A urine test presently based on thin-layer chromatography screening and gas-liquid chromatography (GLC) confirmation has been a practical way of detecting methaqualone use in individuals. A more practical test is the radioimmuno assay for screening and GLC for confirmation. It appears that the drug methaqualone can be easily detected in the urine up to 72 hr after the last dosage. Individuals evaluated after being identified through the urine testing procedure readily admit to the use of illegal drugs and are most cooperative in giving drug abuse data, whether it is Mandrax, hashish, herion, or alcohol. The majority evaluated in this study were not in any program for drug abuse although all but one admitted to frequent drug abuse. The finding has been generally true of the other urinalysis test for drugs of abuse as the majority of the soldiers in the rehabilitation program have been identified by urinalysis over the past year. Because of the uncertainty of surveys on how prevalent was Mandrax use (anywhere from 5 to 90%, depending on who was consulted), a random selection of urines was done in September/November 1973. A total of 7,545 urine samples were tested those 2 months and the results were 2.9 and 3.9% positive respectively. Since that time and through June 1974 approximately 250 urine samples a week were tested for Mandrax based on a special request by the commander who suspected an individual of abusing Mandrax, and approximately 20 to 30% of the samples were positive. During June and July all randomly collected urines were tested and the results on a daily basis were from 1.5 to 3.5%. Since July 1974 no urines have been collected or tested. The follow-up indicates that of this number practically all are clinically confirmed as drug abusers and are entered into the Army's Drug Rehabilitation Program.", "contents": "Methaqualone (Mandrax) abuse, urine testing, and identification: clinical correlation between a new mass urinalysis test and a military drug abuse program. A urine test presently based on thin-layer chromatography screening and gas-liquid chromatography (GLC) confirmation has been a practical way of detecting methaqualone use in individuals. A more practical test is the radioimmuno assay for screening and GLC for confirmation. It appears that the drug methaqualone can be easily detected in the urine up to 72 hr after the last dosage. Individuals evaluated after being identified through the urine testing procedure readily admit to the use of illegal drugs and are most cooperative in giving drug abuse data, whether it is Mandrax, hashish, herion, or alcohol. The majority evaluated in this study were not in any program for drug abuse although all but one admitted to frequent drug abuse. The finding has been generally true of the other urinalysis test for drugs of abuse as the majority of the soldiers in the rehabilitation program have been identified by urinalysis over the past year. Because of the uncertainty of surveys on how prevalent was Mandrax use (anywhere from 5 to 90%, depending on who was consulted), a random selection of urines was done in September/November 1973. A total of 7,545 urine samples were tested those 2 months and the results were 2.9 and 3.9% positive respectively. Since that time and through June 1974 approximately 250 urine samples a week were tested for Mandrax based on a special request by the commander who suspected an individual of abusing Mandrax, and approximately 20 to 30% of the samples were positive. During June and July all randomly collected urines were tested and the results on a daily basis were from 1.5 to 3.5%. Since July 1974 no urines have been collected or tested. The follow-up indicates that of this number practically all are clinically confirmed as drug abusers and are entered into the Army's Drug Rehabilitation Program."} {"id": "PMID:1262092", "title": "The culture of youth and drug abuse in some European countries.", "content": "Old patterns of education are being replaced in some European countries by the different ideological norms of the various groups composing modern society. Youth has lost the sure feeling to belong to a certain culture. Drug abuse primarily represents an attempt to get over this insecurity. In an inquiry in Swiss military schools, recruits were questioned about drug and alcohol use and cigarette smoking, and this was related to the home situation. Juveniles who do not have enough affective support in the primary group seem to be more subject to the conflicts of norms going on in our society. Three general factors seem to be responsible for the drug use among juveniles: (1) the family situation of childhood, (2) the conflicts of norms of the society in which they are involved, and (3) the milieu provocation.", "contents": "The culture of youth and drug abuse in some European countries. Old patterns of education are being replaced in some European countries by the different ideological norms of the various groups composing modern society. Youth has lost the sure feeling to belong to a certain culture. Drug abuse primarily represents an attempt to get over this insecurity. In an inquiry in Swiss military schools, recruits were questioned about drug and alcohol use and cigarette smoking, and this was related to the home situation. Juveniles who do not have enough affective support in the primary group seem to be more subject to the conflicts of norms going on in our society. Three general factors seem to be responsible for the drug use among juveniles: (1) the family situation of childhood, (2) the conflicts of norms of the society in which they are involved, and (3) the milieu provocation."} {"id": "PMID:1262093", "title": "Sex roles and street roles.", "content": "A proposed typology of the street roles of female addicts was tested through interviews with 62 female addicts. Five role types are identified which are distinct from one another and exhaust the range of roles reported by respondents. A number of limitations to the typology are isolated and discussed.", "contents": "Sex roles and street roles. A proposed typology of the street roles of female addicts was tested through interviews with 62 female addicts. Five role types are identified which are distinct from one another and exhaust the range of roles reported by respondents. A number of limitations to the typology are isolated and discussed."} {"id": "PMID:1262094", "title": "The relative effectiveness of a medical hospitalization program vs a feedback-behavior modification program in treating alcohol and drug abusers.", "content": "There is a sparsity of studies specifying the relative effectiveness of different types of treatment programs in treating a similar target population of drug and alcohol abusers in the same locale. In this paper, two drug and alcohol rehabilitation programs are described and their relative effectiveness compared in treating similar target populations. The first treatment program evaluated is a medically oriented hospitalization program and the second is a short-term therapeutic community program, called \"Feedback\" because it is structured on the basis of a collection of feedback and behavior modification principles and techniques. Both programs were implemented by basically the same staff and both treated similar target populations of multiple drug abusers and alcohol abusers during comparable time periods. The results indicated that the feedback program was significantly more effective in rehabilitating multiple drug abusers (nonheroin abusers) than the hospitalization program with regard to three criteria (return to work for 60 days, perform effectively according to the supervisor, and control drug or alcohol problems). But both programs were equally effective in rehabilitating alcohol abusers (problem drinkers and alcoholics).", "contents": "The relative effectiveness of a medical hospitalization program vs a feedback-behavior modification program in treating alcohol and drug abusers. There is a sparsity of studies specifying the relative effectiveness of different types of treatment programs in treating a similar target population of drug and alcohol abusers in the same locale. In this paper, two drug and alcohol rehabilitation programs are described and their relative effectiveness compared in treating similar target populations. The first treatment program evaluated is a medically oriented hospitalization program and the second is a short-term therapeutic community program, called \"Feedback\" because it is structured on the basis of a collection of feedback and behavior modification principles and techniques. Both programs were implemented by basically the same staff and both treated similar target populations of multiple drug abusers and alcohol abusers during comparable time periods. The results indicated that the feedback program was significantly more effective in rehabilitating multiple drug abusers (nonheroin abusers) than the hospitalization program with regard to three criteria (return to work for 60 days, perform effectively according to the supervisor, and control drug or alcohol problems). But both programs were equally effective in rehabilitating alcohol abusers (problem drinkers and alcoholics)."} {"id": "PMID:1262095", "title": "Evaluating outcome criteria used in methadone maintenance programs.", "content": "This report reviews the results of several large methadone maintenance programs and analyzes the outcome measures used. Criteria measures were often vague and sometimes not defined. Many studies base their findings on unverified patient self-report because costs for more reliable and systematic data collection are prohibitive. Available data does not allow for resolution of the pro- or antimethadone maintenance views for treatment of heroin addiction.", "contents": "Evaluating outcome criteria used in methadone maintenance programs. This report reviews the results of several large methadone maintenance programs and analyzes the outcome measures used. Criteria measures were often vague and sometimes not defined. Many studies base their findings on unverified patient self-report because costs for more reliable and systematic data collection are prohibitive. Available data does not allow for resolution of the pro- or antimethadone maintenance views for treatment of heroin addiction."} {"id": "PMID:1262096", "title": "Comparison of psychiatric inpatient male and female adolescent drug abusers.", "content": "Drug-abusing male and female adolescent psychiatric inpatients were compared on a variety of etiological, environmental, and social variables. Results indicated that the frequency, duration, and pattern of abuse did not differ significantly for males and females. Factor analyses, however, revealed that for females, drug abuse and pathology in general were associated with family related variables; for males, patient abuse and patient pathology emerged as factors orthogonal to family drug abuse and family pathology. These findings indicate that female pathology is more reactive to the family situation and hence they raise the hypothesis that when the female separates from the family her pathology will decrease more than the pathology of the male who separates.", "contents": "Comparison of psychiatric inpatient male and female adolescent drug abusers. Drug-abusing male and female adolescent psychiatric inpatients were compared on a variety of etiological, environmental, and social variables. Results indicated that the frequency, duration, and pattern of abuse did not differ significantly for males and females. Factor analyses, however, revealed that for females, drug abuse and pathology in general were associated with family related variables; for males, patient abuse and patient pathology emerged as factors orthogonal to family drug abuse and family pathology. These findings indicate that female pathology is more reactive to the family situation and hence they raise the hypothesis that when the female separates from the family her pathology will decrease more than the pathology of the male who separates."} {"id": "PMID:1262097", "title": "Reliability and validity of self-reported illegal activities and drug use collected from narcotic addicts.", "content": "In follow-up of 1,500 drug-using applicants to the NIMH civil commitment program under Titles I and III of the Narcotic Addict Rehabilitation Act, efforts were made to measure the reliability and validity of self-reported criminal and drug-taking behavior. Various methods to assure reliable and valid responses were developed and implemented. These methods included choice of interviewer, intraquestionnaire safeguards, interview-reinterview procedures, and use of police records and urinalysis reports. Overall, the results indicated that the responses for 829 respondents were reliable. The greatest limitation to the validity study was the incomplete and unreliable police records and urinalysis reports.", "contents": "Reliability and validity of self-reported illegal activities and drug use collected from narcotic addicts. In follow-up of 1,500 drug-using applicants to the NIMH civil commitment program under Titles I and III of the Narcotic Addict Rehabilitation Act, efforts were made to measure the reliability and validity of self-reported criminal and drug-taking behavior. Various methods to assure reliable and valid responses were developed and implemented. These methods included choice of interviewer, intraquestionnaire safeguards, interview-reinterview procedures, and use of police records and urinalysis reports. Overall, the results indicated that the responses for 829 respondents were reliable. The greatest limitation to the validity study was the incomplete and unreliable police records and urinalysis reports."} {"id": "PMID:1262098", "title": "Polydrug use by high-school students: involvement and correlates.", "content": "A hierarchical cluster analysis was performed on 273 self-admitted high-school drug users' descriptions of how frequently they had employed marijuana, stimulants, depressants, hallucinogens, solvents, and opiates during the preceding year. Four types of polydrug users were identified and considered as representing an ordinal scaling of the students along a continuum of overall involvement with drugs, and each user was assigned an index score based on his typal membership. A stepwise multiple regression was then performed to discover which of the students' background characteristics and attitudes were related to their polydrug involvement scores. The search for pleasant sensations, the desire for expanded creativity, and the belief that one would cease taking drugs if they were conclusively shown to be harmful were more powerful predictors of polydrug involvement than any of the sociocultural factors.", "contents": "Polydrug use by high-school students: involvement and correlates. A hierarchical cluster analysis was performed on 273 self-admitted high-school drug users' descriptions of how frequently they had employed marijuana, stimulants, depressants, hallucinogens, solvents, and opiates during the preceding year. Four types of polydrug users were identified and considered as representing an ordinal scaling of the students along a continuum of overall involvement with drugs, and each user was assigned an index score based on his typal membership. A stepwise multiple regression was then performed to discover which of the students' background characteristics and attitudes were related to their polydrug involvement scores. The search for pleasant sensations, the desire for expanded creativity, and the belief that one would cease taking drugs if they were conclusively shown to be harmful were more powerful predictors of polydrug involvement than any of the sociocultural factors."} {"id": "PMID:1262099", "title": "Deliberate hydrocarbon inhalation among low-socioeconomic adolescents not necessarily apprehended by the police.", "content": "Nearly 600 low socioeconomic adolescents were given a 17-item multiple choice questionnaire designed by the authors. Demographic data tended, in some respects, to be consistent with previous research. In other respects there were some differences, e.g., sniffing tends to also be a problem with females. The data suggested that there are differences between chronic and social sniffers and that these differences should be taken into account when designing treatment/prevention programs. Another suggestion is that sniffing tends to be a social activity that is engaged in because (1) it is readily available and (2) it relieves boredom. Prevention programs have tended to focus on making it more difficult to obtain access to solvents, but this has had only limited success. The development of alternatives to neighborhood boredom should also be seen as an integral and important part of drug-abuse prevention.", "contents": "Deliberate hydrocarbon inhalation among low-socioeconomic adolescents not necessarily apprehended by the police. Nearly 600 low socioeconomic adolescents were given a 17-item multiple choice questionnaire designed by the authors. Demographic data tended, in some respects, to be consistent with previous research. In other respects there were some differences, e.g., sniffing tends to also be a problem with females. The data suggested that there are differences between chronic and social sniffers and that these differences should be taken into account when designing treatment/prevention programs. Another suggestion is that sniffing tends to be a social activity that is engaged in because (1) it is readily available and (2) it relieves boredom. Prevention programs have tended to focus on making it more difficult to obtain access to solvents, but this has had only limited success. The development of alternatives to neighborhood boredom should also be seen as an integral and important part of drug-abuse prevention."} {"id": "PMID:1262106", "title": "Diffuse chronic granulomatous mucocutaneous candidiasis.", "content": "A 3-year-old Thai boy with diffuse chronic granulomatous mucocutaneous candidiasis, recurrent bacterial skin infection and adrenal insufficiency is reported. Candida albicans was demonstrated in the dermal granuloma. He had a defect in cell-mediated immunity and was anemic. Although therapy with topical clotrimazole, oral iron, systemic antibiotic and low-dose of prednisone gave a dramatic result, he died of disseminated cryptococcosis.", "contents": "Diffuse chronic granulomatous mucocutaneous candidiasis. A 3-year-old Thai boy with diffuse chronic granulomatous mucocutaneous candidiasis, recurrent bacterial skin infection and adrenal insufficiency is reported. Candida albicans was demonstrated in the dermal granuloma. He had a defect in cell-mediated immunity and was anemic. Although therapy with topical clotrimazole, oral iron, systemic antibiotic and low-dose of prednisone gave a dramatic result, he died of disseminated cryptococcosis."} {"id": "PMID:1262107", "title": "Some notes of an aging nail watcher.", "content": "Growth of deciduous tissues gives us a natural kymograph to record secular trends and in some instances makes the mark on the moving record. For the observant clinician, knowledge of the rate of nail growth may permit an occasional spectacular diagnosis, although much more often it merely adds a small bit to our understanding of simple but basic biological prenciples in health and disease.", "contents": "Some notes of an aging nail watcher. Growth of deciduous tissues gives us a natural kymograph to record secular trends and in some instances makes the mark on the moving record. For the observant clinician, knowledge of the rate of nail growth may permit an occasional spectacular diagnosis, although much more often it merely adds a small bit to our understanding of simple but basic biological prenciples in health and disease."} {"id": "PMID:1262108", "title": "Surveillance of smallpox.", "content": "An intensified global smallpox eradication programme was started by the World Health Organization in 1967. This paper describes the basic techniques employed and the experiences involved in implementing the procedures. Surveillance schemes have varied considerably in detail from country to country according to different health structures, and the emphasis is therefore placed on the more generally used approaches. Finally, important principles in the implementation of the smallpox surveillance programme are considered in relation to the development of such programmes for other communicable diseases.", "contents": "Surveillance of smallpox. An intensified global smallpox eradication programme was started by the World Health Organization in 1967. This paper describes the basic techniques employed and the experiences involved in implementing the procedures. Surveillance schemes have varied considerably in detail from country to country according to different health structures, and the emphasis is therefore placed on the more generally used approaches. Finally, important principles in the implementation of the smallpox surveillance programme are considered in relation to the development of such programmes for other communicable diseases."} {"id": "PMID:1262110", "title": "Surveillance of communicable diseases in tropical Africa.", "content": "In tropical Africa, parasitic and infective diseases remain the predominant causes of mortality and morbidity, and health and epidemiological services are poorly developed. Experience elsewhere has shown the value of surveillance in the control of communicable diseases and this paper contains a brief review of the use of surveillance in tropical African countries and considers the priorities, techniques and constraints of the major programmes.", "contents": "Surveillance of communicable diseases in tropical Africa. In tropical Africa, parasitic and infective diseases remain the predominant causes of mortality and morbidity, and health and epidemiological services are poorly developed. Experience elsewhere has shown the value of surveillance in the control of communicable diseases and this paper contains a brief review of the use of surveillance in tropical African countries and considers the priorities, techniques and constraints of the major programmes."} {"id": "PMID:1262112", "title": "Monitoring communicable disease: vaccination programmes.", "content": "The success of vaccination as a means of disease prevention depends on its appropriate application and its reputation with the profession and the public. Surveillance, by providing accurate information on effectiveness and the frequency and nature of hazards, is essential to this purpose. Several factors that influence the success and safety of vaccination programmes are discussed. The essential elements of a vaccine surveillance scheme are outlined with special reference to experience derived from monitoring vaccines in current use.", "contents": "Monitoring communicable disease: vaccination programmes. The success of vaccination as a means of disease prevention depends on its appropriate application and its reputation with the profession and the public. Surveillance, by providing accurate information on effectiveness and the frequency and nature of hazards, is essential to this purpose. Several factors that influence the success and safety of vaccination programmes are discussed. The essential elements of a vaccine surveillance scheme are outlined with special reference to experience derived from monitoring vaccines in current use."} {"id": "PMID:1262113", "title": "Nutritional surveillance of young children in developing countries.", "content": "This paper discusses simple but effective methods of surveillance of growth and nutrition of children in developing countries where resources are scarce and food shortages most likely to occur. In the youngest age group, the simplest weight-for-age chart, already used, is undoubtedly the best method. Where the age of children is not known, arm circumference provides an acceptable alternative. In older children, arm circumference alone may not be reliable and can be improved by measuring height as well and combining the two results.", "contents": "Nutritional surveillance of young children in developing countries. This paper discusses simple but effective methods of surveillance of growth and nutrition of children in developing countries where resources are scarce and food shortages most likely to occur. In the youngest age group, the simplest weight-for-age chart, already used, is undoubtedly the best method. Where the age of children is not known, arm circumference provides an acceptable alternative. In older children, arm circumference alone may not be reliable and can be improved by measuring height as well and combining the two results."} {"id": "PMID:1262114", "title": "Surveillance in developed countries with particular reference to child growth.", "content": "Surveillance of biological function rather than of disease events is a possible method of detecting early changes in population health. The reasons for and methods of a pilot surveillance scheme of the growth of schoolchildren in Britain are discussed. The study, started in 1972, supports the feasibility of surveillance using simple growth measurements and information provided by parents on self-administered questionnaires. Other possible applications of this type of surveillance include growth and nutrition at other stages of life as related to nutrition intervention programmes, and respiratory function as related to environmental changes or the introduction of new substances such as 'safer' cigarettes.", "contents": "Surveillance in developed countries with particular reference to child growth. Surveillance of biological function rather than of disease events is a possible method of detecting early changes in population health. The reasons for and methods of a pilot surveillance scheme of the growth of schoolchildren in Britain are discussed. The study, started in 1972, supports the feasibility of surveillance using simple growth measurements and information provided by parents on self-administered questionnaires. Other possible applications of this type of surveillance include growth and nutrition at other stages of life as related to nutrition intervention programmes, and respiratory function as related to environmental changes or the introduction of new substances such as 'safer' cigarettes."} {"id": "PMID:1262116", "title": "Surveillance of tuberculosis.", "content": "Surveillance must be an integral part of any effective tuberculosis programme and should be concerned with two distinct subjects--surveillance of the tuberculosis situation and surveillance of control measures applied. This paper describes and discusses these two aspects with regard to both developed and developing countries, and makes recommendations for the collection of reliable surveillance data.", "contents": "Surveillance of tuberculosis. Surveillance must be an integral part of any effective tuberculosis programme and should be concerned with two distinct subjects--surveillance of the tuberculosis situation and surveillance of control measures applied. This paper describes and discusses these two aspects with regard to both developed and developing countries, and makes recommendations for the collection of reliable surveillance data."} {"id": "PMID:1262117", "title": "Surveillance and monitoring of cardiovascular disease: assessment of trends.", "content": "This paper describes the current state of surveillance and monitoring of acute, chronic and asymptomatic cardiovascular disease with particular reference to the situation in Czechoslovakia. It goes on to discuss some of the difficulties involved in obtaining adequate data on which to base surveillance and of creating a coherent central information system. The importance of combining registration or notification with active intervention is emphasized, and the possible suggested of introducing simple techniques of cardiovascular investigation into health screening procedures or consultations established primarily for another purpose.", "contents": "Surveillance and monitoring of cardiovascular disease: assessment of trends. This paper describes the current state of surveillance and monitoring of acute, chronic and asymptomatic cardiovascular disease with particular reference to the situation in Czechoslovakia. It goes on to discuss some of the difficulties involved in obtaining adequate data on which to base surveillance and of creating a coherent central information system. The importance of combining registration or notification with active intervention is emphasized, and the possible suggested of introducing simple techniques of cardiovascular investigation into health screening procedures or consultations established primarily for another purpose."} {"id": "PMID:1262118", "title": "Against Popperized epidemiology.", "content": "The recommendation of Popper's philosophy of science should be adopted by epidemiologists is disputed. Reference is made to other authors who have shown that the most constructive elements in Popper's ideas have been advocated by earlier philosophers and have been used in epidemiology without abandoning inductive reasoning. It is argued that Popper's denigration of inductive methods is particularly harmful to epidemiology. Inductive reasoning and statistical inference play a key role in the science; it is suggested that unfamiliarity with these ideas contributes to widespread misunderstanding of the function of epidemiology. Attention is drawn to a common fallacy involving correlations between three random variables. The prevalence of the fallacy may be related to confusion between deductive and inductive logic.", "contents": "Against Popperized epidemiology. The recommendation of Popper's philosophy of science should be adopted by epidemiologists is disputed. Reference is made to other authors who have shown that the most constructive elements in Popper's ideas have been advocated by earlier philosophers and have been used in epidemiology without abandoning inductive reasoning. It is argued that Popper's denigration of inductive methods is particularly harmful to epidemiology. Inductive reasoning and statistical inference play a key role in the science; it is suggested that unfamiliarity with these ideas contributes to widespread misunderstanding of the function of epidemiology. Attention is drawn to a common fallacy involving correlations between three random variables. The prevalence of the fallacy may be related to confusion between deductive and inductive logic."} {"id": "PMID:1262130", "title": "New isoprenologs of vitamin K2 series in Sarcina lutea.", "content": "Four new menaquinone homologs have been isolated and characterized from Sarcina lutea. The use of purified silica gel G in the isolation of pure menquinones from bacterial nonpolar lipids has been developed. During this procedure, fractionation of any naturally occuring menaquinones with sidechain variation takes place. The structures of the isolated menaquinones have been elucidated by UV-, and mass spectrometry, and by their corresponding hydroquinones and layer chromatography properties. Thus, Sarcina lutea has been shown to produce four homologs of dihydromenaquinones, i.e., dihydromenaquinone-6,-7,-8, and -9.", "contents": "New isoprenologs of vitamin K2 series in Sarcina lutea. Four new menaquinone homologs have been isolated and characterized from Sarcina lutea. The use of purified silica gel G in the isolation of pure menquinones from bacterial nonpolar lipids has been developed. During this procedure, fractionation of any naturally occuring menaquinones with sidechain variation takes place. The structures of the isolated menaquinones have been elucidated by UV-, and mass spectrometry, and by their corresponding hydroquinones and layer chromatography properties. Thus, Sarcina lutea has been shown to produce four homologs of dihydromenaquinones, i.e., dihydromenaquinone-6,-7,-8, and -9."} {"id": "PMID:1262131", "title": "The \"ideal\" daily vitamin A intake.", "content": "This approach suggests that the healthier the sample, the greater the daily vitamin A intake. Under the conditions of this experiment, approximately 33,000 I.U. of vitamin A may be designated as the \"ideal\" daily allowance. This is almost seven times the RDA of 5000 I.U. for the adult male and eight times higher than the 4000 I.U. RDA for adult females. It is recognized that the \"ideal\" is nonexistent as a theoretic end-point since there is biochemical individuality and because the art of measuring leaves much to be desired. Nonetheless, the technique utilized here provides a mechanism and a goal not previously considered.", "contents": "The \"ideal\" daily vitamin A intake. This approach suggests that the healthier the sample, the greater the daily vitamin A intake. Under the conditions of this experiment, approximately 33,000 I.U. of vitamin A may be designated as the \"ideal\" daily allowance. This is almost seven times the RDA of 5000 I.U. for the adult male and eight times higher than the 4000 I.U. RDA for adult females. It is recognized that the \"ideal\" is nonexistent as a theoretic end-point since there is biochemical individuality and because the art of measuring leaves much to be desired. Nonetheless, the technique utilized here provides a mechanism and a goal not previously considered."} {"id": "PMID:1262132", "title": "Pyrithiamine-induced thiamine deficiency: effects on rat myelination.", "content": "Pyrithiamine was administered to newborn rats throughout the vulnerable period for myelinogenesis. A major metabolic defect was produced in the cerebral activities of the thiamine-dependent enzymes, transketolase and pyruvate decarboxylase. In spite of a defect in carbohydrate metabolism which is lethal in adult rats, overall development, and myelination as indicated by biochemical and morphological criteria, proceeded at an essentially normal rate. These findings indicate alternative metabolic pathways may be operational in newborn rat brain enabling it to circumvent major blockage in thiamine-dependent reactions.", "contents": "Pyrithiamine-induced thiamine deficiency: effects on rat myelination. Pyrithiamine was administered to newborn rats throughout the vulnerable period for myelinogenesis. A major metabolic defect was produced in the cerebral activities of the thiamine-dependent enzymes, transketolase and pyruvate decarboxylase. In spite of a defect in carbohydrate metabolism which is lethal in adult rats, overall development, and myelination as indicated by biochemical and morphological criteria, proceeded at an essentially normal rate. These findings indicate alternative metabolic pathways may be operational in newborn rat brain enabling it to circumvent major blockage in thiamine-dependent reactions."} {"id": "PMID:1262133", "title": "Absence of influence of high doses of biotin on reproductive performance in female rats.", "content": "Biotin at 2 doses totalling 5 and 50 mg/kg s.c. does not disturb the reproductive performance of the female rats 1-6 weeks after treatment. The number of implantations and resorptions as well as the weights of placentas and foetuses remain normal. The ovaries do not show weight or histological alterations. Vaginal cycle and readiness to mate remain undisturbed.", "contents": "Absence of influence of high doses of biotin on reproductive performance in female rats. Biotin at 2 doses totalling 5 and 50 mg/kg s.c. does not disturb the reproductive performance of the female rats 1-6 weeks after treatment. The number of implantations and resorptions as well as the weights of placentas and foetuses remain normal. The ovaries do not show weight or histological alterations. Vaginal cycle and readiness to mate remain undisturbed."} {"id": "PMID:1262134", "title": "Interaction of erythorbic acid with ascorbic acid catabolism.", "content": "After a vitamin C depletion period of 12 days supplementing erythorbic acid (50 mg/day/kg bodyweight) over 16 days significantly accelerated the catabolism of a newly ingested tracer dose of (1-14C) ascorbic aicd in guinea pigs in comparison to animals supplemented with ascorbic acid (5 mg/day/kg bodyweight), but this effect of erythorbic acid could not be normalized by additional supplementation with ascorbic acid. Half-lives for (1-14C) ascorbic acid (50% of the dose excreted) were drastically reduced from 97 h to 50 h and 59 h, respectively. Also figures on the retention of radioactivity showed the availability of ascorbic acid to be reduced. This is in accordance with the significant reduction in size of ascorbic acid bodypool, and in weight gain in the groups receiving erythorbic acid, or erythorbic and ascorbic acids. The bioavailability was calculated to be strongly depressed to nearly 50% of the total ingested biologically active material (ascorbic plus erythorbic acids), assuming erythorbic acid to have only one-twentieth of the biological activity of ascorbic acid.", "contents": "Interaction of erythorbic acid with ascorbic acid catabolism. After a vitamin C depletion period of 12 days supplementing erythorbic acid (50 mg/day/kg bodyweight) over 16 days significantly accelerated the catabolism of a newly ingested tracer dose of (1-14C) ascorbic aicd in guinea pigs in comparison to animals supplemented with ascorbic acid (5 mg/day/kg bodyweight), but this effect of erythorbic acid could not be normalized by additional supplementation with ascorbic acid. Half-lives for (1-14C) ascorbic acid (50% of the dose excreted) were drastically reduced from 97 h to 50 h and 59 h, respectively. Also figures on the retention of radioactivity showed the availability of ascorbic acid to be reduced. This is in accordance with the significant reduction in size of ascorbic acid bodypool, and in weight gain in the groups receiving erythorbic acid, or erythorbic and ascorbic acids. The bioavailability was calculated to be strongly depressed to nearly 50% of the total ingested biologically active material (ascorbic plus erythorbic acids), assuming erythorbic acid to have only one-twentieth of the biological activity of ascorbic acid."} {"id": "PMID:1262136", "title": "The \"ideal\" daily niacin intake.", "content": "This approach indicates that the healthier the sample, the greater the niacin intake. Under the conditions of this experiment, approximately 115 mg of niacin may be designated as the \"ideal\" daily allowance. This is six or seven times the RDA of 12 to 20mg for adult males and females. It is recognized that the \"ideal\" as a theoretic endpoint is nonexistent since there is biochemical individuality and because the art of measuring leaves much to be desired. Nonetheless, the technique utilized here provides a mechanism and a goal not previously considered.", "contents": "The \"ideal\" daily niacin intake. This approach indicates that the healthier the sample, the greater the niacin intake. Under the conditions of this experiment, approximately 115 mg of niacin may be designated as the \"ideal\" daily allowance. This is six or seven times the RDA of 12 to 20mg for adult males and females. It is recognized that the \"ideal\" as a theoretic endpoint is nonexistent since there is biochemical individuality and because the art of measuring leaves much to be desired. Nonetheless, the technique utilized here provides a mechanism and a goal not previously considered."} {"id": "PMID:1262137", "title": "Blood values of some vitamins in long-stay psycho-geriatric patients.", "content": "A group of 18 long-stay hospital psycho-geriatric patients (aged 64-101 years) and a group of 10 healthy elderly subjects (aged 53-67 years) who were living in their own residence were studied. The group of geriatric patients were suffering from some degree of pressure sores, dementia, irritability and anorexia. Biochemical tests on vitamin adequacy with particular references to ascorbic acid, thiamine and retinal were performed in the subjects. The thiamine status was measured by determining the thiamine pyrophosphate stimulating effect of transketolase enzyme activity in whole blood. The ascorbic acid and retinal nutritures were determined by measuring their levels in plasma. From the biochemical data of the vitamins it would appear that a significant proportion of the long-stay hospital psycho-geriatric patients may be at risk of thiamine, ascorbic acid and retinol deficiencies.", "contents": "Blood values of some vitamins in long-stay psycho-geriatric patients. A group of 18 long-stay hospital psycho-geriatric patients (aged 64-101 years) and a group of 10 healthy elderly subjects (aged 53-67 years) who were living in their own residence were studied. The group of geriatric patients were suffering from some degree of pressure sores, dementia, irritability and anorexia. Biochemical tests on vitamin adequacy with particular references to ascorbic acid, thiamine and retinal were performed in the subjects. The thiamine status was measured by determining the thiamine pyrophosphate stimulating effect of transketolase enzyme activity in whole blood. The ascorbic acid and retinal nutritures were determined by measuring their levels in plasma. From the biochemical data of the vitamins it would appear that a significant proportion of the long-stay hospital psycho-geriatric patients may be at risk of thiamine, ascorbic acid and retinol deficiencies."} {"id": "PMID:1262139", "title": "Hypocalcemic development in high and low calcium-adapted chicks during acute calcium deficiency.", "content": "Chickens were adapted to either a high or low calcium intake and then subjected to an acute calcium deficiency by feeding ground yellow corn +/- phosphate. Hypocalcemia developed within 3-5 h in those chicks given the corn plus phosphate. The response was about equal in the high and low adapted animals suggesting that the effect was not mediated via regulatory factors such as parathyroid hormone or thyrocalcitonin intervention. Rather, it is suggested that the influence of phosphate is direct and may be due to an enhancement of calcium movement from the fluids to the bone. The high calcium adapted chicks also exhibited some hypocalcemia in response to eating corn without phosphate supplementation. This development, contrary to the other cases, appeared to be due to a lag in calcium regulating mechanisms. The low calcium adaptation did not seem to influence growth within the timespan used, but there was a significant reduction in bone ash values and of adrenal enlargement. Thus, it was evident that the low and high calcium diets were different in regards to calcium metabolism and it appears that the low calcium intake may have been stressful.", "contents": "Hypocalcemic development in high and low calcium-adapted chicks during acute calcium deficiency. Chickens were adapted to either a high or low calcium intake and then subjected to an acute calcium deficiency by feeding ground yellow corn +/- phosphate. Hypocalcemia developed within 3-5 h in those chicks given the corn plus phosphate. The response was about equal in the high and low adapted animals suggesting that the effect was not mediated via regulatory factors such as parathyroid hormone or thyrocalcitonin intervention. Rather, it is suggested that the influence of phosphate is direct and may be due to an enhancement of calcium movement from the fluids to the bone. The high calcium adapted chicks also exhibited some hypocalcemia in response to eating corn without phosphate supplementation. This development, contrary to the other cases, appeared to be due to a lag in calcium regulating mechanisms. The low calcium adaptation did not seem to influence growth within the timespan used, but there was a significant reduction in bone ash values and of adrenal enlargement. Thus, it was evident that the low and high calcium diets were different in regards to calcium metabolism and it appears that the low calcium intake may have been stressful."} {"id": "PMID:1262138", "title": "An evaluation in rats of nutritional status and reproduction performance post oral contraceptive therapy.", "content": "Adult female rats were orally administered either 0.052, 0.26 mg of Enovoid E (OC) or the vehicle, propylene glycol. Thereafter they were mated six, thirteen or twenty-seven days after the discontinuation of the drug. Chemical analyses i.e. cholesterol levels in plasma, liver and adrenals; tocopherol levels in plasma and liver; fatty acid patterns of cholesteryl esters of plasma liver, and adrenals, and plasma lipoproteins distribution, were performed on the pre-breeding (post-OC) females, mothers (following weaning of the young) and young female progeny, 10 weeks after weaning. Weanlings derived from mothers previously exposed to OC weighed more than their counterparts from mothers who had not been given the drug. A slight decrease of the survival time of the young during lactation was also observed in groups treated with higher levels of OC. Liver weights were increased in mothers as a result of pregnancy and lactation. Observed elevations of plasma cholesterol levels and cholesteryl arachidonate in the livers of the progeny were probably due to prolonged exposure to the 15% corn oil diet. In addition, previously reported metabolic effects of OC, such as increases in liver cholesteryl oleate, decreases in plasma and adrenal cholesteryl arachidonate, decreases in the alpha/beta lipoprotein ratio and alpha-tocopherol levels in plasma were confirmed.", "contents": "An evaluation in rats of nutritional status and reproduction performance post oral contraceptive therapy. Adult female rats were orally administered either 0.052, 0.26 mg of Enovoid E (OC) or the vehicle, propylene glycol. Thereafter they were mated six, thirteen or twenty-seven days after the discontinuation of the drug. Chemical analyses i.e. cholesterol levels in plasma, liver and adrenals; tocopherol levels in plasma and liver; fatty acid patterns of cholesteryl esters of plasma liver, and adrenals, and plasma lipoproteins distribution, were performed on the pre-breeding (post-OC) females, mothers (following weaning of the young) and young female progeny, 10 weeks after weaning. Weanlings derived from mothers previously exposed to OC weighed more than their counterparts from mothers who had not been given the drug. A slight decrease of the survival time of the young during lactation was also observed in groups treated with higher levels of OC. Liver weights were increased in mothers as a result of pregnancy and lactation. Observed elevations of plasma cholesterol levels and cholesteryl arachidonate in the livers of the progeny were probably due to prolonged exposure to the 15% corn oil diet. In addition, previously reported metabolic effects of OC, such as increases in liver cholesteryl oleate, decreases in plasma and adrenal cholesteryl arachidonate, decreases in the alpha/beta lipoprotein ratio and alpha-tocopherol levels in plasma were confirmed."} {"id": "PMID:1262140", "title": "[Absorption and metabolic efficiency of iron in nickel deficiency].", "content": "Absorption and Metabolic Efficiency of Iron During Ni Deficiency. Ni deficiency leads to reduced iron contents in organs and to greatly reduced Hb levels and erythrocyte counts. Using models it was studied whether this Ni-dependent Fe anemia can be attributed to an impaired absorption of iron or to its metabolic efficiency. An experiment with seven 30-day-old rats from each of two generations were used for this. In Ni deficiency (0.015 ppm dietary nickel) iron absorption was clearly impaired at both 50 ppm and 100 ppm iron in the diet. Compared to the groups given 20 ppm nickel, the amount of iron absorbed fell two-thirds and one-third, respectively. By comparison, the influence on the metabolic efficiency of the iron was relatively small; at high iron supply, however, it was reduced by 8% in the Ni-deficient animals. Therefore, the reduced levels of hemoglobin, erythrocytes and hematocrit must essentially be caused by the impared absorption.", "contents": "[Absorption and metabolic efficiency of iron in nickel deficiency]. Absorption and Metabolic Efficiency of Iron During Ni Deficiency. Ni deficiency leads to reduced iron contents in organs and to greatly reduced Hb levels and erythrocyte counts. Using models it was studied whether this Ni-dependent Fe anemia can be attributed to an impaired absorption of iron or to its metabolic efficiency. An experiment with seven 30-day-old rats from each of two generations were used for this. In Ni deficiency (0.015 ppm dietary nickel) iron absorption was clearly impaired at both 50 ppm and 100 ppm iron in the diet. Compared to the groups given 20 ppm nickel, the amount of iron absorbed fell two-thirds and one-third, respectively. By comparison, the influence on the metabolic efficiency of the iron was relatively small; at high iron supply, however, it was reduced by 8% in the Ni-deficient animals. Therefore, the reduced levels of hemoglobin, erythrocytes and hematocrit must essentially be caused by the impared absorption."} {"id": "PMID:1262144", "title": "Visceral angiography. A community hospital experience.", "content": "Selective visceral angiography is well within the ability of small community hospitals. If carefully performed by a well-trained interested radiologist, the procedures carry negligible morbidity and mortality. These studies can provide an exact diagnosis, a working differential or at least enough data to plan a surgical approach with accuracy. Nine cases in which the angiographic diagnosis was vital to the patients' care have been presented.", "contents": "Visceral angiography. A community hospital experience. Selective visceral angiography is well within the ability of small community hospitals. If carefully performed by a well-trained interested radiologist, the procedures carry negligible morbidity and mortality. These studies can provide an exact diagnosis, a working differential or at least enough data to plan a surgical approach with accuracy. Nine cases in which the angiographic diagnosis was vital to the patients' care have been presented."} {"id": "PMID:1262146", "title": "Concomitant prophylactic inferior vena caval clipping.", "content": "Fatal pulmonary embolism is a common complication of any major surgery, especially in high risk patients. Experimental work in animals showed definite impairment of myocardial function after inferior vena caval ligation, but no changes after clipping. During the last four years, we have used concomitant vena caval clipping as a prophylactic measure in major abdominal vascular procedures. No added mortality or morbidity has occurred because of clipping per se and no deaths were due to pulmonary embolism. We recommend concomitant prophylactic clipping as an adjunctive procedure for all laparotomy patients who are prone to pulmonary embolism.", "contents": "Concomitant prophylactic inferior vena caval clipping. Fatal pulmonary embolism is a common complication of any major surgery, especially in high risk patients. Experimental work in animals showed definite impairment of myocardial function after inferior vena caval ligation, but no changes after clipping. During the last four years, we have used concomitant vena caval clipping as a prophylactic measure in major abdominal vascular procedures. No added mortality or morbidity has occurred because of clipping per se and no deaths were due to pulmonary embolism. We recommend concomitant prophylactic clipping as an adjunctive procedure for all laparotomy patients who are prone to pulmonary embolism."} {"id": "PMID:1262147", "title": "Jejunal mucosal graft with transhepatic intubation. Rodney Smith's technic for very high strictures of the hepatic duct.", "content": "Very high hepatic strictures present a difficult surgical problem. Restenosis frequently occurs even when the best method has been applied. Rodney Smith developed a method of transhepatic intubation in association with a jejunal mucosal graft through which the transhepatic tube is passed and fixed. We applied this technic in two cases and consider the results obtained to be very satisfactory. The patients have been followed for four and 3-1/2 years respectively.", "contents": "Jejunal mucosal graft with transhepatic intubation. Rodney Smith's technic for very high strictures of the hepatic duct. Very high hepatic strictures present a difficult surgical problem. Restenosis frequently occurs even when the best method has been applied. Rodney Smith developed a method of transhepatic intubation in association with a jejunal mucosal graft through which the transhepatic tube is passed and fixed. We applied this technic in two cases and consider the results obtained to be very satisfactory. The patients have been followed for four and 3-1/2 years respectively."} {"id": "PMID:1262148", "title": "Clinical review of 106 consecutive carotid endarterectomies.", "content": "We have reviewed 106 consecutive carotid endarterectomies performed from 1966 through 1973. During this period, 99 elective procedures and seven emergency procedures were done on 84 patients, 22 of whom had bilateral endarterectomies. Indications for elective procedures included transient ischemic attacks, emboli from ulcerative plaques, high grade stenotic plaques on the same or opposite side in patients with old cerebrovascular accidents and asymptomatic bruits. Seven patients had emergency endarterectomies performed for acute strokes and these demonstrated a higher risk. They were grouped together as emergency procedures for comparison with the 99 elective procedures. Previous histories, risk factors, complications and outcome in the two groups are presented and discussed. Mortality in the elective cases was 2%, compared to 30% in the emergency cases with acute stroke. Surgical indications, operative technic and immediate and late results are discussed.", "contents": "Clinical review of 106 consecutive carotid endarterectomies. We have reviewed 106 consecutive carotid endarterectomies performed from 1966 through 1973. During this period, 99 elective procedures and seven emergency procedures were done on 84 patients, 22 of whom had bilateral endarterectomies. Indications for elective procedures included transient ischemic attacks, emboli from ulcerative plaques, high grade stenotic plaques on the same or opposite side in patients with old cerebrovascular accidents and asymptomatic bruits. Seven patients had emergency endarterectomies performed for acute strokes and these demonstrated a higher risk. They were grouped together as emergency procedures for comparison with the 99 elective procedures. Previous histories, risk factors, complications and outcome in the two groups are presented and discussed. Mortality in the elective cases was 2%, compared to 30% in the emergency cases with acute stroke. Surgical indications, operative technic and immediate and late results are discussed."} {"id": "PMID:1262150", "title": "Unusual problems in renal hypertension.", "content": "Ten cases of renal hypertension with uncommon causes were presented and unusual problems in their diagnosis and surgical management were discussed. These causes included segmental stenosis involving aberrant renal artery, renal artery stenosis in association with renal arteriovenous fistula, postoperative renal hypertension and hypertension secondary to renal tuberculosis. A high index of clinical suspicion and increasing awareness will help in diagnosing such rare and unusual cases of renal hypertension.", "contents": "Unusual problems in renal hypertension. Ten cases of renal hypertension with uncommon causes were presented and unusual problems in their diagnosis and surgical management were discussed. These causes included segmental stenosis involving aberrant renal artery, renal artery stenosis in association with renal arteriovenous fistula, postoperative renal hypertension and hypertension secondary to renal tuberculosis. A high index of clinical suspicion and increasing awareness will help in diagnosing such rare and unusual cases of renal hypertension."} {"id": "PMID:1262153", "title": "The value of endoscopic retrograde opacification of biliary-pancreatic ducts in icterus.", "content": "Important progress in the last few years in fiberscopic instrumentation for digestive endoscopy has made possible duodenoscopy with catheterization of the papilla to obtain retrograde biliopancreatic contrast x-rays. Up to now the only possible way to explore biliary ducts, in icterus, was surgically. This new method makes their study possible without any surgical intervention and with a simple neuroleptanalgesia. It is most advantageous in icterus where clinical tests, laboratory tests and other complementary examinations such as laparoscopy do not help to determine the cause. This examination is not devoid of dangers, particularly of the risk of cholangitis and pancreatitis and therefore certain technical precautions are necessary, e.g., immediate surgical intervention in case of organ obstruction and well defined indications.", "contents": "The value of endoscopic retrograde opacification of biliary-pancreatic ducts in icterus. Important progress in the last few years in fiberscopic instrumentation for digestive endoscopy has made possible duodenoscopy with catheterization of the papilla to obtain retrograde biliopancreatic contrast x-rays. Up to now the only possible way to explore biliary ducts, in icterus, was surgically. This new method makes their study possible without any surgical intervention and with a simple neuroleptanalgesia. It is most advantageous in icterus where clinical tests, laboratory tests and other complementary examinations such as laparoscopy do not help to determine the cause. This examination is not devoid of dangers, particularly of the risk of cholangitis and pancreatitis and therefore certain technical precautions are necessary, e.g., immediate surgical intervention in case of organ obstruction and well defined indications."} {"id": "PMID:1262154", "title": "Sacrococcygeal teratoma in the neonate.", "content": "Three cases of sacrococcygeal teratoma of the neonate occurred during a two-year period in which approximately 6,000 live births occurred in our hospital. Two infants were delivered vaginally and one by cesarean section. One infant underwent immediate surgery and survived, whereas the other two were in too poor condition to warrant surgery. Early excision is the treatment of choice; radiotherapy and chemotherapy are not effective in the malignant variety of sacrococcygeal lesion.", "contents": "Sacrococcygeal teratoma in the neonate. Three cases of sacrococcygeal teratoma of the neonate occurred during a two-year period in which approximately 6,000 live births occurred in our hospital. Two infants were delivered vaginally and one by cesarean section. One infant underwent immediate surgery and survived, whereas the other two were in too poor condition to warrant surgery. Early excision is the treatment of choice; radiotherapy and chemotherapy are not effective in the malignant variety of sacrococcygeal lesion."} {"id": "PMID:1262158", "title": "The effects of ophthalmic drugs, vehicles, and preservatives on corneal epithelium: a scanning electron microscope study.", "content": "Scanning electron microscopy was found to be of considerable use in evaluating the effects of various commonly used drugs, vehicles, and preservatives on the corneal surface. Of the preparations tested 0.3 per cent gentamicin caused many central cellular microvilli to stand up prominently. Moderate losses of peripheral microvilli, with mild superficial cellular desquamation was noted with 0.25 per cent phospholine iodide, 2 per cent pilocarpine, 2 per cent fluorescein, and Fluor-I-Strip. The top layer of epithelial cells desquamated with 4 per cent cocaine or neopolycin treatment. The top two layers of cells were lost when 0.01 per cent benzalkonium chloride was instilled. When cell death occurred severe membrane disruption was accompanied by loss of microvilli and rupture of intercellular tight junctions. These studies show that the cytotoxicity of topical ocular preparations can be tested in an in vivo model and evaluated by scanning electron microscopy.", "contents": "The effects of ophthalmic drugs, vehicles, and preservatives on corneal epithelium: a scanning electron microscope study. Scanning electron microscopy was found to be of considerable use in evaluating the effects of various commonly used drugs, vehicles, and preservatives on the corneal surface. Of the preparations tested 0.3 per cent gentamicin caused many central cellular microvilli to stand up prominently. Moderate losses of peripheral microvilli, with mild superficial cellular desquamation was noted with 0.25 per cent phospholine iodide, 2 per cent pilocarpine, 2 per cent fluorescein, and Fluor-I-Strip. The top layer of epithelial cells desquamated with 4 per cent cocaine or neopolycin treatment. The top two layers of cells were lost when 0.01 per cent benzalkonium chloride was instilled. When cell death occurred severe membrane disruption was accompanied by loss of microvilli and rupture of intercellular tight junctions. These studies show that the cytotoxicity of topical ocular preparations can be tested in an in vivo model and evaluated by scanning electron microscopy."} {"id": "PMID:1262159", "title": "Human alpha-crystallin. I. The isolation and characterization of newly synthesized alpha-crystallin.", "content": "Studies of the incorporation of 14C amino acids into human lens proteins demonstrate that an alpha-crystallin fraction takes up more than six times as much radioactivity as any other lens protein. Based on analyses with a calibrated Bio-Gel A-1.5 m column, a molecular weight of 4.9 x 10(5) +/- 5 per cent was obtained for this protein while sedimentation equilibrium analyses indicated a weight average molecular weight, Mw, of 7.5 x 10(5) +/- 4 per cent at 10,000 r.p.m. Gel electrophoresis in sodium dodecyl sulfate revealed two components with molecular weights of 22,000 and 20,000, values similar to those found with calf alpha-crystallin. Alkaline urea gel electrophoresis indicated one major polypeptide with a mobility similar to the B2 chain of calf alpha-crystallin and two major bands with mobilities between those of the calf alpha-crystallin A2 and A1 chains. Amino acid analyses of this newly synthesized alpha-crystallin gave a composition which with a few exceptions is very similar to that of calf alpha-crystallin. All three major polypeptides contained 14C amino acids. However, from the present data, it cannot be determined whether the three polypeptides were independently synthesized or a rapid transformation produced one of the labeled polypeptides in the A region. There appears to be between three and four times as many presumptive A as B polypeptides.", "contents": "Human alpha-crystallin. I. The isolation and characterization of newly synthesized alpha-crystallin. Studies of the incorporation of 14C amino acids into human lens proteins demonstrate that an alpha-crystallin fraction takes up more than six times as much radioactivity as any other lens protein. Based on analyses with a calibrated Bio-Gel A-1.5 m column, a molecular weight of 4.9 x 10(5) +/- 5 per cent was obtained for this protein while sedimentation equilibrium analyses indicated a weight average molecular weight, Mw, of 7.5 x 10(5) +/- 4 per cent at 10,000 r.p.m. Gel electrophoresis in sodium dodecyl sulfate revealed two components with molecular weights of 22,000 and 20,000, values similar to those found with calf alpha-crystallin. Alkaline urea gel electrophoresis indicated one major polypeptide with a mobility similar to the B2 chain of calf alpha-crystallin and two major bands with mobilities between those of the calf alpha-crystallin A2 and A1 chains. Amino acid analyses of this newly synthesized alpha-crystallin gave a composition which with a few exceptions is very similar to that of calf alpha-crystallin. All three major polypeptides contained 14C amino acids. However, from the present data, it cannot be determined whether the three polypeptides were independently synthesized or a rapid transformation produced one of the labeled polypeptides in the A region. There appears to be between three and four times as many presumptive A as B polypeptides."} {"id": "PMID:1262160", "title": "Cytochemical studies on endogenous peroxidase in conjunctival and corneal epithelial cells.", "content": "Endogenous peroxidase activity in conjunctival and corneal epithelial cells was studied cytochemically by the diaminobenzidine method. Many peroxidase-positive cells were found in the fornical conjunctiva. They were also seen, but less frequently, in the tarsal conjunctiva, limbus, and cornea. Three types of peroxidase-positive (cytochemically reactive) cells were differentiated besides goblet cells: (1) the most superficial cells with several reactive secretory granules (2) moth-eaten cells near the surface with abundant reactive microgranules, and (3) deeper cells with reactive microgranules and a few densely reactive granules. Some goblet cells shared the same characteristics with other types of cells. The relationship among these cells, functional differences between granules, and the function of peroxidase are discussed.", "contents": "Cytochemical studies on endogenous peroxidase in conjunctival and corneal epithelial cells. Endogenous peroxidase activity in conjunctival and corneal epithelial cells was studied cytochemically by the diaminobenzidine method. Many peroxidase-positive cells were found in the fornical conjunctiva. They were also seen, but less frequently, in the tarsal conjunctiva, limbus, and cornea. Three types of peroxidase-positive (cytochemically reactive) cells were differentiated besides goblet cells: (1) the most superficial cells with several reactive secretory granules (2) moth-eaten cells near the surface with abundant reactive microgranules, and (3) deeper cells with reactive microgranules and a few densely reactive granules. Some goblet cells shared the same characteristics with other types of cells. The relationship among these cells, functional differences between granules, and the function of peroxidase are discussed."} {"id": "PMID:1262161", "title": "Corneal membrane water permeability as a function of temperature.", "content": "Osmotically driven water flow across the corneal epithelium and endothelium has been measured as a function of temperature. For both membranes deviations from a single straight-line relationship are found in a logarithmic plot of hydraulic conductivity against 1/T. Both membranes show a high (14 to 16 kcal per mole) apparent activation energy at temperatures between 23 degrees C. and 5 degrees C. At higher temperatures, between 23 degrees C. and 37 degrees C., the apparent activation energy falls to 5.7 and 9.3 kcal per mole for the epithelium and endothelium, respectively. The low value for the apparent activation energy for water crossing the epithelium and endothelium at normal corneal temperatures presumably reflects water passage through water-filled channels.", "contents": "Corneal membrane water permeability as a function of temperature. Osmotically driven water flow across the corneal epithelium and endothelium has been measured as a function of temperature. For both membranes deviations from a single straight-line relationship are found in a logarithmic plot of hydraulic conductivity against 1/T. Both membranes show a high (14 to 16 kcal per mole) apparent activation energy at temperatures between 23 degrees C. and 5 degrees C. At higher temperatures, between 23 degrees C. and 37 degrees C., the apparent activation energy falls to 5.7 and 9.3 kcal per mole for the epithelium and endothelium, respectively. The low value for the apparent activation energy for water crossing the epithelium and endothelium at normal corneal temperatures presumably reflects water passage through water-filled channels."} {"id": "PMID:1262162", "title": "Objective evaluation of experimental ocular irritation.", "content": "After topically administered nitrogen mustard the irritative effect on the pupil, intraocular pressure, protein concentration of the aqueous humor and on the vessels of the iris and conjunctiva was quantified. The protein level in aqueous was determined by refractometry. The degree of hyperemia of conjunctiva and iris was determined by measuring the amount of Evans blue dye present in the tissue minutes after intravenous administration. A reproducible relationship was obtained using these methods to evaluate the degree of irritation produced by nitrogen mustard.", "contents": "Objective evaluation of experimental ocular irritation. After topically administered nitrogen mustard the irritative effect on the pupil, intraocular pressure, protein concentration of the aqueous humor and on the vessels of the iris and conjunctiva was quantified. The protein level in aqueous was determined by refractometry. The degree of hyperemia of conjunctiva and iris was determined by measuring the amount of Evans blue dye present in the tissue minutes after intravenous administration. A reproducible relationship was obtained using these methods to evaluate the degree of irritation produced by nitrogen mustard."} {"id": "PMID:1262163", "title": "Intraocular lysozyme in experimental uveitis in rabbits: aqueous and vitreous assay.", "content": "We determined normal aqueous and vitreous lysozyme levels in rabbit eyes and induced experimental uveitis to record the uppermost aqueous and vitreous lysozyme levels. The normal aqueous humor of the rabbit eye contained 1.05 mug per milliliter lysozyme and the normal vitreous humor contained 0.45 mug per milliliter. After the intravitreal administration of a foreign protein, the aqueous and vitreous lysozyme levels rose within one day, reaching maximum values of 38.4 mug per milliliter and 114 mug per milliliter, respectively, at 14 days, and subsequently declining to minimal values by 28 days after injection.", "contents": "Intraocular lysozyme in experimental uveitis in rabbits: aqueous and vitreous assay. We determined normal aqueous and vitreous lysozyme levels in rabbit eyes and induced experimental uveitis to record the uppermost aqueous and vitreous lysozyme levels. The normal aqueous humor of the rabbit eye contained 1.05 mug per milliliter lysozyme and the normal vitreous humor contained 0.45 mug per milliliter. After the intravitreal administration of a foreign protein, the aqueous and vitreous lysozyme levels rose within one day, reaching maximum values of 38.4 mug per milliliter and 114 mug per milliliter, respectively, at 14 days, and subsequently declining to minimal values by 28 days after injection."} {"id": "PMID:1262164", "title": "Congenital total external ophthalmoplegia associated with infantile spinal muscular atrophy. Fine structure of extraocular muscle.", "content": "A case of total congenital external ophthalmoplegia associated with infantile spinal muscular atrophy is presented. In the first 29 months of life, ophthalmoplegia has remained complete. Ultrastructure of lateral rectus extraocular muscle indicates a neurogenic process as the basis of the ophthalmoplegia. Light microscopy alone is insufficient to distinguish primary \"myopathic\" from \"neurogenic\" disease in external eye muscles.", "contents": "Congenital total external ophthalmoplegia associated with infantile spinal muscular atrophy. Fine structure of extraocular muscle. A case of total congenital external ophthalmoplegia associated with infantile spinal muscular atrophy is presented. In the first 29 months of life, ophthalmoplegia has remained complete. Ultrastructure of lateral rectus extraocular muscle indicates a neurogenic process as the basis of the ophthalmoplegia. Light microscopy alone is insufficient to distinguish primary \"myopathic\" from \"neurogenic\" disease in external eye muscles."} {"id": "PMID:1262165", "title": "Organic cation uptake in vitro by the rabbit iris-ciliary body, renal cortex, and choroid plexus.", "content": "The uptake in vitro of radioactively labeled test substances was studied in tissues from albino rabbits. Choroid plexus, slices of outer renal cortex, and iris-ciliary body were incubated in a K-rich medium containing one of the cations 14C-Emepronium (Cetiprin), 14C-tetraethylammonium, 14C-choline, or 125I-o-iodobenzyltrimethylammonium and sometimes the anions 131I-o-iodohippurate and 125I-iodipamide. Choroid plexus and renal cortex accumulated all test substances, some to very high tissue-medium ratios. The iris-ciliary body preparation accumulated the anions well but the organic cations only weakly. The only convincing uptake was that of Emepronium. The affinity of this uptake system seemed to be similar to that in the kidney, half-saturating around 10(-4)M Emepronium.", "contents": "Organic cation uptake in vitro by the rabbit iris-ciliary body, renal cortex, and choroid plexus. The uptake in vitro of radioactively labeled test substances was studied in tissues from albino rabbits. Choroid plexus, slices of outer renal cortex, and iris-ciliary body were incubated in a K-rich medium containing one of the cations 14C-Emepronium (Cetiprin), 14C-tetraethylammonium, 14C-choline, or 125I-o-iodobenzyltrimethylammonium and sometimes the anions 131I-o-iodohippurate and 125I-iodipamide. Choroid plexus and renal cortex accumulated all test substances, some to very high tissue-medium ratios. The iris-ciliary body preparation accumulated the anions well but the organic cations only weakly. The only convincing uptake was that of Emepronium. The affinity of this uptake system seemed to be similar to that in the kidney, half-saturating around 10(-4)M Emepronium."} {"id": "PMID:1262166", "title": "Studies of aqueous humor dynamics in man. V. Effects of acetazolamide and isoproterenol in young and old normal volunteers.", "content": "Young and old volunteers received acetazolamide systemically or isoproterenol topically. Although the responses of the two groups of volunteers were quite similar for acetazolamide, they differed significantly for isoproterenol. It is suggested that a normal aging change is altered responsiveness of the site of aqueous production and of the outflow pathways to topical isoproterenol. The site of aqueous production becomes less responsive; the outflow pathways become more responsive.", "contents": "Studies of aqueous humor dynamics in man. V. Effects of acetazolamide and isoproterenol in young and old normal volunteers. Young and old volunteers received acetazolamide systemically or isoproterenol topically. Although the responses of the two groups of volunteers were quite similar for acetazolamide, they differed significantly for isoproterenol. It is suggested that a normal aging change is altered responsiveness of the site of aqueous production and of the outflow pathways to topical isoproterenol. The site of aqueous production becomes less responsive; the outflow pathways become more responsive."} {"id": "PMID:1262167", "title": "The rates of movement of Na+, Cl-, and HCO-3 from plasma to posterior chamber: effect of acetazolamide and relation to the treatment of glaucoma.", "content": "The rates of accession of sodium and chloride, and the formation of bicarbonate into the posterior chamber have been studied in normal dogs, and following complete inhibition of carbonic anhydrase by acetazolamide, 50 mg. per kilogram. Sodium accession approximated fluid formation rate and was reduced 30 per cent by acetazolamide. Bicarbonate formation was reduced to one-third the control value by the inhibitor; chloride was unaffected. Reduction of accession was 1.9 mM per minute for sodium and 1.6 mM per minute for bicarbonate, showing that these are stoichiometrically linked. These results, together with other data in fish and rabbit, support the idea that bicarbonate formation is a general function of ciliary epithelia and, through its effect on sodium, is the basis for a considerable component of fluid movement into the eye. Inhibition of bicarbonate formation appears to be the pharmacological basis for the treatment of glaucoma by carbonic anhydrase inhibitors.", "contents": "The rates of movement of Na+, Cl-, and HCO-3 from plasma to posterior chamber: effect of acetazolamide and relation to the treatment of glaucoma. The rates of accession of sodium and chloride, and the formation of bicarbonate into the posterior chamber have been studied in normal dogs, and following complete inhibition of carbonic anhydrase by acetazolamide, 50 mg. per kilogram. Sodium accession approximated fluid formation rate and was reduced 30 per cent by acetazolamide. Bicarbonate formation was reduced to one-third the control value by the inhibitor; chloride was unaffected. Reduction of accession was 1.9 mM per minute for sodium and 1.6 mM per minute for bicarbonate, showing that these are stoichiometrically linked. These results, together with other data in fish and rabbit, support the idea that bicarbonate formation is a general function of ciliary epithelia and, through its effect on sodium, is the basis for a considerable component of fluid movement into the eye. Inhibition of bicarbonate formation appears to be the pharmacological basis for the treatment of glaucoma by carbonic anhydrase inhibitors."} {"id": "PMID:1262168", "title": "Aqueous humor dynamics in glaucomato-cyclitic crisis.", "content": "The transfer coefficients of fluorescein in the anterior chamber by flow, kfa, and by diffusion, kdpa, can be calculated for an individual human eye, through an analysis of fluorescein concentrations in the anterior chamber, pupillary aqueous, and serum ultrafiltrates following intravenous injection. Using this technique, aqueous humor dynamics was studied in eight patients with glaucomato-cyclitic crisis. In seven patients, the coefficients determined during the attacks averaged 1.23 +/- 0.08 (S.E.M.) X 10(-2) min.-1 for kfa and 3.51 +/- 0.81 X 10(-3) min.-1 for kdpa in the involved eye, and 0.91 +/- 0.12 X 10(-2) min.-1 for kfa and 1.36 +/- 0.39 X 10(-3) min.-1 for kdpa in the fellow eye. The differences in the coefficients between the two eyes were statistically significant (P less than 0.05). In six patients, the coefficients were measured during the remission, giving average values of 0.81 +/- 0.08 X 10(-2) min.-1 for kfa and 1.36 +/- 0.16 X 10(-3) min.-1 for kdpa in the involved eye, and 0.78 +/- 0.07 X 10(-2) min.-1 for kfa and 1.20 +/- 0.10 X 10(-3) min.-1 for kdpa in the fellow eye. The differences in the coeficients between the two eyes were not significant. In five patients, the determinations were repeated during the attack and remission, and the differences in the coefficients between both phases were statistically significant (P less than 0.05) in the involved eye.", "contents": "Aqueous humor dynamics in glaucomato-cyclitic crisis. The transfer coefficients of fluorescein in the anterior chamber by flow, kfa, and by diffusion, kdpa, can be calculated for an individual human eye, through an analysis of fluorescein concentrations in the anterior chamber, pupillary aqueous, and serum ultrafiltrates following intravenous injection. Using this technique, aqueous humor dynamics was studied in eight patients with glaucomato-cyclitic crisis. In seven patients, the coefficients determined during the attacks averaged 1.23 +/- 0.08 (S.E.M.) X 10(-2) min.-1 for kfa and 3.51 +/- 0.81 X 10(-3) min.-1 for kdpa in the involved eye, and 0.91 +/- 0.12 X 10(-2) min.-1 for kfa and 1.36 +/- 0.39 X 10(-3) min.-1 for kdpa in the fellow eye. The differences in the coefficients between the two eyes were statistically significant (P less than 0.05). In six patients, the coefficients were measured during the remission, giving average values of 0.81 +/- 0.08 X 10(-2) min.-1 for kfa and 1.36 +/- 0.16 X 10(-3) min.-1 for kdpa in the involved eye, and 0.78 +/- 0.07 X 10(-2) min.-1 for kfa and 1.20 +/- 0.10 X 10(-3) min.-1 for kdpa in the fellow eye. The differences in the coeficients between the two eyes were not significant. In five patients, the determinations were repeated during the attack and remission, and the differences in the coefficients between both phases were statistically significant (P less than 0.05) in the involved eye."} {"id": "PMID:1262169", "title": "The effect of dopamine on the intraocular pressure and pupil of the rabbit eye.", "content": "The presence of a dopamine-specific receptor that can influence intraocular pressure in the rabbit eye is suggested by these experiments: intravitreal, systemic, or topically administered dopamine solutions can produce a decrease in intraocular pressure that is dose-dependent. In high doses the decrease in intraocular pressure is accompanied by mydriasis, and alpha-adrenergic pupillary response. This alpha-response may be caused by dopamine as a direct, but weak alpha-stimulator or by displacement of norepinephrine onto the receptor from its storage site. At lower doses the decrease in intraocular pressure occurs in the absence of mydriasis and in spite of blockade of beta-adrenergic receptors. Further, a specific dopaminergic blocker, haloperidol, prevents this decrease in intraocular pressure. The decreases are small, but reproducible and suggest that dopamine can influence the adrenergic regulation of intraocular pressure.", "contents": "The effect of dopamine on the intraocular pressure and pupil of the rabbit eye. The presence of a dopamine-specific receptor that can influence intraocular pressure in the rabbit eye is suggested by these experiments: intravitreal, systemic, or topically administered dopamine solutions can produce a decrease in intraocular pressure that is dose-dependent. In high doses the decrease in intraocular pressure is accompanied by mydriasis, and alpha-adrenergic pupillary response. This alpha-response may be caused by dopamine as a direct, but weak alpha-stimulator or by displacement of norepinephrine onto the receptor from its storage site. At lower doses the decrease in intraocular pressure occurs in the absence of mydriasis and in spite of blockade of beta-adrenergic receptors. Further, a specific dopaminergic blocker, haloperidol, prevents this decrease in intraocular pressure. The decreases are small, but reproducible and suggest that dopamine can influence the adrenergic regulation of intraocular pressure."} {"id": "PMID:1262170", "title": "Human alpha-crystallin-III isolation and characterization of protein from normal infant lenses and old lens peripheries.", "content": "Alpha-crystallin isolated from the peripheries of old normal or cataractous lenses appears to be identical, consisting of eleven polypeptides, five B, and six A chains. In contrast, alpha-crystallin isolated from normal six-week-old human lenses has only three major polypeptides, corresponding to B1, A1, and A2 of the old human lens protein as well as small amounts of some of the other components. Comparisons with bovine alpha-crystallin are also reported. Based on gel filtration experiments with Bio-Gel A-1.5m, two distinct populations of alpha-crystallin were found in old lens periphery, one containing species greater than 1.5 X 10(6) daltons and another of approximately 9 X 10(5) daltons. In the cataract preparations, the higher molecular weight fraction is predominant. This fraction is not present in young lenses.", "contents": "Human alpha-crystallin-III isolation and characterization of protein from normal infant lenses and old lens peripheries. Alpha-crystallin isolated from the peripheries of old normal or cataractous lenses appears to be identical, consisting of eleven polypeptides, five B, and six A chains. In contrast, alpha-crystallin isolated from normal six-week-old human lenses has only three major polypeptides, corresponding to B1, A1, and A2 of the old human lens protein as well as small amounts of some of the other components. Comparisons with bovine alpha-crystallin are also reported. Based on gel filtration experiments with Bio-Gel A-1.5m, two distinct populations of alpha-crystallin were found in old lens periphery, one containing species greater than 1.5 X 10(6) daltons and another of approximately 9 X 10(5) daltons. In the cataract preparations, the higher molecular weight fraction is predominant. This fraction is not present in young lenses."} {"id": "PMID:1262171", "title": "Differential sensitivity at the cellular level in primary open-angle glaucoma: prednisolone and ouabain.", "content": "The concentration of drug necessary to inhibit lymphocyte transformation by 50 per cent (I50 value) was determined for the glucocorticoid prednisolone-21-phosphate, and for the sodium-potassium adenosinetriphosphatase inhibitor ouabain, in 37 persons representing the full range of ocular and cellular glucocorticoid sensitivity. The lymphocytes of patients with primary open-angle glaucoma, and of high ocular responders to glucocorticoids, were more sensitive to prednisolone-21-phosphate than were those of ocular low and intermediate responders. By contrast, there was no significant difference in sensitivity to ouabain. There was also no significant correlation of lymphocyte sensitivity to prednisolone-21-phosphate with that to ouabain. These results provide indirect evidence that the increased cellular sensitivity to glucocorticoids in primary open-angle glaucoma is a specific effect, and not merely representative of a general vulnerability of \"sick cells.\"", "contents": "Differential sensitivity at the cellular level in primary open-angle glaucoma: prednisolone and ouabain. The concentration of drug necessary to inhibit lymphocyte transformation by 50 per cent (I50 value) was determined for the glucocorticoid prednisolone-21-phosphate, and for the sodium-potassium adenosinetriphosphatase inhibitor ouabain, in 37 persons representing the full range of ocular and cellular glucocorticoid sensitivity. The lymphocytes of patients with primary open-angle glaucoma, and of high ocular responders to glucocorticoids, were more sensitive to prednisolone-21-phosphate than were those of ocular low and intermediate responders. By contrast, there was no significant difference in sensitivity to ouabain. There was also no significant correlation of lymphocyte sensitivity to prednisolone-21-phosphate with that to ouabain. These results provide indirect evidence that the increased cellular sensitivity to glucocorticoids in primary open-angle glaucoma is a specific effect, and not merely representative of a general vulnerability of \"sick cells.\""} {"id": "PMID:1262172", "title": "Effect of long-wave ultraviolet light on the lens. I. Model systems for detecting and measuring effect on the lens in vitro.", "content": "Rat mouse, and chick lenses incubated with 3-aminotriazole under long-wave ultraviolet (UV) show reduced accumulation and incorporation of leucine and a loss of glutathione. The effect on leucine incorporation is strikingly enhanced when capsule-epithelium pools are incubated. The procedure may identify photosensitizers or metabolic inhibitors which are cataractogenic when acting in conjunction with UV.", "contents": "Effect of long-wave ultraviolet light on the lens. I. Model systems for detecting and measuring effect on the lens in vitro. Rat mouse, and chick lenses incubated with 3-aminotriazole under long-wave ultraviolet (UV) show reduced accumulation and incorporation of leucine and a loss of glutathione. The effect on leucine incorporation is strikingly enhanced when capsule-epithelium pools are incubated. The procedure may identify photosensitizers or metabolic inhibitors which are cataractogenic when acting in conjunction with UV."} {"id": "PMID:1262173", "title": "Xerophthalmia.", "content": "Some characteristics of children with xerophthalmia are described and the difference in age between those with serious corneal xerophthalmia and those showing milder conjunctival xerophthalmia is noted. The various public health measures instituted to prevent xerophthalmia are examined. The particular importance of protein in food given to severely malnourished children suffering from xerophthalmia is stressed and studies on enzyme activities which are enhanced in the xerophthalmic cornea are briefly noted.", "contents": "Xerophthalmia. Some characteristics of children with xerophthalmia are described and the difference in age between those with serious corneal xerophthalmia and those showing milder conjunctival xerophthalmia is noted. The various public health measures instituted to prevent xerophthalmia are examined. The particular importance of protein in food given to severely malnourished children suffering from xerophthalmia is stressed and studies on enzyme activities which are enhanced in the xerophthalmic cornea are briefly noted."} {"id": "PMID:1262174", "title": "Lens growth in the Nakano mouse.", "content": "The growth curve of the lens of the Nakano mouse was compared to that of the normal mouse. There was no obvious difference for the first two weeks of age. After this period the growth of the normal lens continued while that of Nakano mouse lens slowed abruptly and eventually ceased. Studies with labeled leucine, however, showed that even after the appearance of the \"pin-head\" opacity the protein synthesis, although depressed, continued. These findings combined with previous histological observations suggest that new fiber formation is probably unaffected in the early stages of the Nakano cataract. The apparent cessation of lens growth is probably associated with the extensive liquefaction that is observed to occur at the posterior nuclear region.", "contents": "Lens growth in the Nakano mouse. The growth curve of the lens of the Nakano mouse was compared to that of the normal mouse. There was no obvious difference for the first two weeks of age. After this period the growth of the normal lens continued while that of Nakano mouse lens slowed abruptly and eventually ceased. Studies with labeled leucine, however, showed that even after the appearance of the \"pin-head\" opacity the protein synthesis, although depressed, continued. These findings combined with previous histological observations suggest that new fiber formation is probably unaffected in the early stages of the Nakano cataract. The apparent cessation of lens growth is probably associated with the extensive liquefaction that is observed to occur at the posterior nuclear region."} {"id": "PMID:1262175", "title": "The thickness of the human lens cortex in the different types of senile cataract.", "content": "In every type of beginning senile cataract the cortex of the lens measured with the slit lamp appears thinner than the normal lens cortex in the same age group. The decreased rate of fiber formation and of proteosynthesis precedes the first appearance of lens opacities.", "contents": "The thickness of the human lens cortex in the different types of senile cataract. In every type of beginning senile cataract the cortex of the lens measured with the slit lamp appears thinner than the normal lens cortex in the same age group. The decreased rate of fiber formation and of proteosynthesis precedes the first appearance of lens opacities."} {"id": "PMID:1262176", "title": "Incorporation of glutamic acid into soluble protein as a function of age.", "content": "The incorporation of U-14C glutamic acid into soluble bovine and human lens protein fractions has been studied as a function of age. Culture technique and DEAE cellulose fractionation has been used. In bovine lenses the incorporation of glutamic acid into alpha and gamma crystallins decreased with age whereas in the beta crystallin group the specific activities remained constant. All protein fractions of the human lenses showed a gradual reduction of the incorporation of the radioactive amino acid between 40 and 74 years of age. The highest specific activity was found to correspond to Spector's HL protein and its existence is confirmed throughout the whole human life-span.", "contents": "Incorporation of glutamic acid into soluble protein as a function of age. The incorporation of U-14C glutamic acid into soluble bovine and human lens protein fractions has been studied as a function of age. Culture technique and DEAE cellulose fractionation has been used. In bovine lenses the incorporation of glutamic acid into alpha and gamma crystallins decreased with age whereas in the beta crystallin group the specific activities remained constant. All protein fractions of the human lenses showed a gradual reduction of the incorporation of the radioactive amino acid between 40 and 74 years of age. The highest specific activity was found to correspond to Spector's HL protein and its existence is confirmed throughout the whole human life-span."} {"id": "PMID:1262177", "title": "A study of the distribution and origin of myoinositol in the cornea of the rabbit.", "content": "The concentration of inositol in the cornea of the rabbit is about one millimole per kilogram tissue water, a level eight- to tenfold that of the aqueous humor. The present study shows that its concentration in the stroma is about the same as in the epithelium and endothelium. Uptake of 2-3H inositol by the corneal layers above the level in the medium was demonstrated in vitro, but the low ratios obtained do not exclusively indicate active transport of the compound. Synthesis of inositol from glucose by the cornea was shown and the estimated rate is compatible with the hypothesis that inositol originates in the cornea and diffuses across the endothelium to the aqueous humor.", "contents": "A study of the distribution and origin of myoinositol in the cornea of the rabbit. The concentration of inositol in the cornea of the rabbit is about one millimole per kilogram tissue water, a level eight- to tenfold that of the aqueous humor. The present study shows that its concentration in the stroma is about the same as in the epithelium and endothelium. Uptake of 2-3H inositol by the corneal layers above the level in the medium was demonstrated in vitro, but the low ratios obtained do not exclusively indicate active transport of the compound. Synthesis of inositol from glucose by the cornea was shown and the estimated rate is compatible with the hypothesis that inositol originates in the cornea and diffuses across the endothelium to the aqueous humor."} {"id": "PMID:1262178", "title": "Ultrastructural effects of Conray 60 and Pantopaque on ependyma and choroid plexus following intraventricular injections.", "content": "Electron microscope evaluation of choroid plexus and ependyma following single cerebral intraventricular injections of Conray 60 and Pantopaque was carried out on 35 rats and 4 dogs. The animals were sacrificed at periods ranging from 1 hour to 4 months. Conray was not detected with the light or electron microscope; however, Pantopaque was presumptively localized as electron-dense masses associated with lipid-like bodies at the ventricular interface of both choroidal and ependymal epithelium. Conray 60 injections consistently induced convulsions in rats. Histological studies demonstrated moderate cellular damage and multilayered proliferation of ependymal epithelium. Morphological damage following Pantopaque was more severe and widespread in both choroid plexus and ependyma suggesting that, of the two agents, Conray may have the greater clinical potential provided that the associated convulsions are controlled by appropriate measures.", "contents": "Ultrastructural effects of Conray 60 and Pantopaque on ependyma and choroid plexus following intraventricular injections. Electron microscope evaluation of choroid plexus and ependyma following single cerebral intraventricular injections of Conray 60 and Pantopaque was carried out on 35 rats and 4 dogs. The animals were sacrificed at periods ranging from 1 hour to 4 months. Conray was not detected with the light or electron microscope; however, Pantopaque was presumptively localized as electron-dense masses associated with lipid-like bodies at the ventricular interface of both choroidal and ependymal epithelium. Conray 60 injections consistently induced convulsions in rats. Histological studies demonstrated moderate cellular damage and multilayered proliferation of ependymal epithelium. Morphological damage following Pantopaque was more severe and widespread in both choroid plexus and ependyma suggesting that, of the two agents, Conray may have the greater clinical potential provided that the associated convulsions are controlled by appropriate measures."} {"id": "PMID:1262183", "title": "The nephrogram of normovolemic, renal artery hypotension.", "content": "Experimental hemorrhagic hypotension results in a prolonged nephrogram during excretory urography. We evaluated the effect of reduced renal perfusion pressure on the nephrogram in normovolemic dogs. Renal artery perfusion pressure to one kidney was reduced to 40-50 mm Hg by inflating a renal artery balloon catheter. Subsequent urograms were qualitatively assessed for nephrographic density. Plasma and urinary iodine concentrations were determined by fluorescent excitation analysis. Total renal blood flow (TRBF) and its intrarenal distribution were assessed with isotopically labeled microspheres. In the majority of dogs severe oliguria and a prolonged and increasingly dense nephrogram were produced in the kidney exposed to reduced perfusion pressure. The nephrogram of the contralateral, normotensive kidney rapidly diminished in density, associated with the excretion of a large volume of dilute urine. The total urinary iodine excreted in 60 min was significantly less than that excreted by both kidneys in control experiments. TRBF to the hypotensive kidney was significantly reduced from its control level, and the percentage of TRBF perfusing the outer cortex decreased.", "contents": "The nephrogram of normovolemic, renal artery hypotension. Experimental hemorrhagic hypotension results in a prolonged nephrogram during excretory urography. We evaluated the effect of reduced renal perfusion pressure on the nephrogram in normovolemic dogs. Renal artery perfusion pressure to one kidney was reduced to 40-50 mm Hg by inflating a renal artery balloon catheter. Subsequent urograms were qualitatively assessed for nephrographic density. Plasma and urinary iodine concentrations were determined by fluorescent excitation analysis. Total renal blood flow (TRBF) and its intrarenal distribution were assessed with isotopically labeled microspheres. In the majority of dogs severe oliguria and a prolonged and increasingly dense nephrogram were produced in the kidney exposed to reduced perfusion pressure. The nephrogram of the contralateral, normotensive kidney rapidly diminished in density, associated with the excretion of a large volume of dilute urine. The total urinary iodine excreted in 60 min was significantly less than that excreted by both kidneys in control experiments. TRBF to the hypotensive kidney was significantly reduced from its control level, and the percentage of TRBF perfusing the outer cortex decreased."} {"id": "PMID:1262184", "title": "Metrizamide in experimental urography. IV. Effects of bilateral ureteric stasis on urine iodine concentration after intravenous infection of an ionic and a non-ionic contrast medium.", "content": "The non-ionic contrast medium metrizamide was compared to the sodium salt of diatrizoate to investigate the potential usefulness of metrizamide in clinical urography when ureteric stasis is applied. After intravenous injection of the contrast media to rabbits at dose level 175 mg I/kg, the kidneys were subjected to temporary bilateral ureteric stasis. Urine was collected through ureteric catheters and analyzed for its concentration of iodine, sodium and potassium. After metrizamide injection the urine iodine concentration was twice as high as after sodium diatrizoate injection. This difference between one non-ionic and one ionic contrast medium was larger than what has been reported earlier during free flow of urine at the same dose. Furthermore, during the periods of ureteric stasis metrizamide was excreted faster than diatrizoate. When diatrizoate was given as its sodium salt, the sodium given was excreted at about the same rate as the diatrizoate given.", "contents": "Metrizamide in experimental urography. IV. Effects of bilateral ureteric stasis on urine iodine concentration after intravenous infection of an ionic and a non-ionic contrast medium. The non-ionic contrast medium metrizamide was compared to the sodium salt of diatrizoate to investigate the potential usefulness of metrizamide in clinical urography when ureteric stasis is applied. After intravenous injection of the contrast media to rabbits at dose level 175 mg I/kg, the kidneys were subjected to temporary bilateral ureteric stasis. Urine was collected through ureteric catheters and analyzed for its concentration of iodine, sodium and potassium. After metrizamide injection the urine iodine concentration was twice as high as after sodium diatrizoate injection. This difference between one non-ionic and one ionic contrast medium was larger than what has been reported earlier during free flow of urine at the same dose. Furthermore, during the periods of ureteric stasis metrizamide was excreted faster than diatrizoate. When diatrizoate was given as its sodium salt, the sodium given was excreted at about the same rate as the diatrizoate given."} {"id": "PMID:1262185", "title": "Experimental renal artery thromboembolism.", "content": "The natural history of experimental renal artery embolism with autogenous thrombus in 16 mongrel dogs has been investigated by sequential selective renal angiography and correlated with examination of the kidneys following autopsy. Angiography in the early (0-24 hr) post-thromboembolism period shows evidence of arterial obstruction and/or spasm which progressively disappears leaving no apparent permanent damage. However, within one or two weeks arterial and nephrographic changes and loss of renal size are discernible by careful comparison with the pre-embolism angiogram. At autopsy multiple disseminated microscopic infarcts involving the convoluted tubules were demonstrable in all cases. Occasionally large wedge-shaped infarcts involving the full thickness of the cortex were superadded. The potential importance of these findings relating to angiographic technique and assessment of treatment of renal thromboembolism is discussed.", "contents": "Experimental renal artery thromboembolism. The natural history of experimental renal artery embolism with autogenous thrombus in 16 mongrel dogs has been investigated by sequential selective renal angiography and correlated with examination of the kidneys following autopsy. Angiography in the early (0-24 hr) post-thromboembolism period shows evidence of arterial obstruction and/or spasm which progressively disappears leaving no apparent permanent damage. However, within one or two weeks arterial and nephrographic changes and loss of renal size are discernible by careful comparison with the pre-embolism angiogram. At autopsy multiple disseminated microscopic infarcts involving the convoluted tubules were demonstrable in all cases. Occasionally large wedge-shaped infarcts involving the full thickness of the cortex were superadded. The potential importance of these findings relating to angiographic technique and assessment of treatment of renal thromboembolism is discussed."} {"id": "PMID:1262179", "title": "In vivo measurement of hepatic iodine concentration using fluorescent excitation analysis.", "content": "Hepatic iodine concentration was measured in the live dog by external use of fluorescent excitation analysis. The number of characteristic photons produced by interaction of exciting radiation from an americium-241 source with iodine within the tissue is proportional to the tissue iodine concentrations. A correction is made for absorption of radiation by the abdominal wall and other tissues lying between the volume of liver being assayed and the detector collimator. The technique is applicable to the in vivo measurement of iodine concentrations from 0.5 to 40 mg/g. Accuracy of the technique is approximately +/- 10%, which is within the range of variation in iodine concentration at various sites within the liver. Radiation dose is low, and radiolabeled tracer compounds need not be used.", "contents": "In vivo measurement of hepatic iodine concentration using fluorescent excitation analysis. Hepatic iodine concentration was measured in the live dog by external use of fluorescent excitation analysis. The number of characteristic photons produced by interaction of exciting radiation from an americium-241 source with iodine within the tissue is proportional to the tissue iodine concentrations. A correction is made for absorption of radiation by the abdominal wall and other tissues lying between the volume of liver being assayed and the detector collimator. The technique is applicable to the in vivo measurement of iodine concentrations from 0.5 to 40 mg/g. Accuracy of the technique is approximately +/- 10%, which is within the range of variation in iodine concentration at various sites within the liver. Radiation dose is low, and radiolabeled tracer compounds need not be used."} {"id": "PMID:1262180", "title": "Comparison of left ventricular ejection fraction and regional contractility fraction pre and post coronary angiography.", "content": "Thirty patients [four normals, eight with mild and 18 with severe coronary artery disease (CAD)] were studied to evaluate left ventricular function type and post coronary angiography. The end diastolic volume (EDV), end systolic volume (ESV), ejection fraction (EF) and the regional contractility fractions (RCF) of eight ventricular segments were evaluated by left ventriculography. The RCF's were analyzed, in addition to the EF's to ascertain the effect of contrast material upon normal and scarred or ischemic segments of the left ventricle, and to rule out spurious findings in the EF due to coexistent reciprocal changes in RCF's. There was good correlation (r = .45 to .97 and p less than .01 to less than .001) in the above parameters of left ventricular function in patients with and without CAD before and after angiography. Thus, although intraventricular and intracoronary injections of contrast material produce transient changes in myocardial contractility, in a clinical setting left ventriculography may be performed prior to or following coronary angiography without danger of spurious results in normals and in patients with CAD.", "contents": "Comparison of left ventricular ejection fraction and regional contractility fraction pre and post coronary angiography. Thirty patients [four normals, eight with mild and 18 with severe coronary artery disease (CAD)] were studied to evaluate left ventricular function type and post coronary angiography. The end diastolic volume (EDV), end systolic volume (ESV), ejection fraction (EF) and the regional contractility fractions (RCF) of eight ventricular segments were evaluated by left ventriculography. The RCF's were analyzed, in addition to the EF's to ascertain the effect of contrast material upon normal and scarred or ischemic segments of the left ventricle, and to rule out spurious findings in the EF due to coexistent reciprocal changes in RCF's. There was good correlation (r = .45 to .97 and p less than .01 to less than .001) in the above parameters of left ventricular function in patients with and without CAD before and after angiography. Thus, although intraventricular and intracoronary injections of contrast material produce transient changes in myocardial contractility, in a clinical setting left ventriculography may be performed prior to or following coronary angiography without danger of spurious results in normals and in patients with CAD."} {"id": "PMID:1262186", "title": "Measurement of histamine, complement components and immune complexes during patient reactions to iodinated contrast material.", "content": "Studies were performed on nine patients who had just suffered urticarial or bronchospastic reactions following injection of iodinated contrast material (ICM). The parameters studied were white cell histamine, serum complement components C'3 and C'4 and circulating immune complexes. The white cells of the nine patients demonstrated an average increase of 125% in intracellular histamine over the 3-4 week period following the ICM reaction. Control volunteers averaged only a 10% change. The data implies that there was a loss of white cell histamine during the ICM reaction with replenishment during the following 3-4 week period. Complement components C'3 and C'4 were normal. Circulating antigen-antibody complexes were sought via precipitin bands in agar gel using Clq. None could be isolated following seven ICM reactions. Thus these ICM reactions appeared to release histamine without detection of circulating immune complexes and with normal levels of two major complement components.", "contents": "Measurement of histamine, complement components and immune complexes during patient reactions to iodinated contrast material. Studies were performed on nine patients who had just suffered urticarial or bronchospastic reactions following injection of iodinated contrast material (ICM). The parameters studied were white cell histamine, serum complement components C'3 and C'4 and circulating immune complexes. The white cells of the nine patients demonstrated an average increase of 125% in intracellular histamine over the 3-4 week period following the ICM reaction. Control volunteers averaged only a 10% change. The data implies that there was a loss of white cell histamine during the ICM reaction with replenishment during the following 3-4 week period. Complement components C'3 and C'4 were normal. Circulating antigen-antibody complexes were sought via precipitin bands in agar gel using Clq. None could be isolated following seven ICM reactions. Thus these ICM reactions appeared to release histamine without detection of circulating immune complexes and with normal levels of two major complement components."} {"id": "PMID:1262200", "title": "High renin activity accompanying angiotensin II inhibition in rats with ischemic renal failure.", "content": "Acute renal failure was produced in rats by right nephrectomy and total occlusion of the left renal artery for 70 min. Angiotensin II competitive inhibitor, P113 (1-sar-8-ala-angiotensin II), was administered intravascularly for 100 min, starting 15 min before the clamping of the renal artery. A marked rise in plasma renin activity was observed 15 min after declamping and was significantly higher in the P113-treated rats than in saline-treated animals. The rise in plasma renin activity was observed 15 min after declamping and was similar in the two groups, indicating that P113 does not prevent the development of acute renal failure in this experimental model. It is suggested that the marked rise in plasma renin activity may be due to interruption of the normal feedback mechanisms which suppress renin release, as a result of occupation of the angiotensin II receptor sites by P113.", "contents": "High renin activity accompanying angiotensin II inhibition in rats with ischemic renal failure. Acute renal failure was produced in rats by right nephrectomy and total occlusion of the left renal artery for 70 min. Angiotensin II competitive inhibitor, P113 (1-sar-8-ala-angiotensin II), was administered intravascularly for 100 min, starting 15 min before the clamping of the renal artery. A marked rise in plasma renin activity was observed 15 min after declamping and was significantly higher in the P113-treated rats than in saline-treated animals. The rise in plasma renin activity was observed 15 min after declamping and was similar in the two groups, indicating that P113 does not prevent the development of acute renal failure in this experimental model. It is suggested that the marked rise in plasma renin activity may be due to interruption of the normal feedback mechanisms which suppress renin release, as a result of occupation of the angiotensin II receptor sites by P113."} {"id": "PMID:1262201", "title": "Heat-enhanced radioresponse in HeLa cells.", "content": "The response of HeLa cells to X-irradiation increases when the cells are irradiated at elevated temperatures or when irradiation is followed by hyperthermia. The magnitude of this thermal effect increases with increasing temperature and varies inversely with dose rate during exposure of the cells to the combined treatment. Enhancement of the radioresponse by postirradiation incubation at elevated temperatures increases with increased incubation time. The results suggest that in HeLa cells the synergistic interaction between hyperthermia and irradiation is due to interference with the repair of potentially lethal damage and/or enhanced expression of lethal damage.", "contents": "Heat-enhanced radioresponse in HeLa cells. The response of HeLa cells to X-irradiation increases when the cells are irradiated at elevated temperatures or when irradiation is followed by hyperthermia. The magnitude of this thermal effect increases with increasing temperature and varies inversely with dose rate during exposure of the cells to the combined treatment. Enhancement of the radioresponse by postirradiation incubation at elevated temperatures increases with increased incubation time. The results suggest that in HeLa cells the synergistic interaction between hyperthermia and irradiation is due to interference with the repair of potentially lethal damage and/or enhanced expression of lethal damage."} {"id": "PMID:1262202", "title": "Human chorionic gonadotropin stimulation of Leydig cell function in puberty. Comparison of testosterone response in plasma and urine.", "content": "The plasma and urinary testosterone response to one i.m. injection of 5,000 IU human chorionic gonadotropin (HCG) was tested in 45 children and adolescents of several diagnostic entities: testosterone was measured before the injection and on the second, fourth and sixth days thereafter. It was found that there was a better correlation between the testosterone concentrations and the different pubertal stages than between testosterone concentration and either chronological or skeletal age. In the children with normal pubertal development, there was a slight rise in basal testosterone concentration with the progression of the pubertal stages. HCG caused a rise in plasma and urinary testosterone: this response was more marked in pubertal stages 4 and 5. The urinary response was variable whereas the changes in plasma testosterone concentration were more constant. In children and adolescents with primary or secondary hypogonadism, the basal levels of testosterone were low or undetectable and there was only a slight response to the single dose of HCG. It was concluded that a single i.m. injection of 5,000 IU HCG and the determination of plasma testosterone before, and two and four days after injection is a useful screening test for Leydig cell function.", "contents": "Human chorionic gonadotropin stimulation of Leydig cell function in puberty. Comparison of testosterone response in plasma and urine. The plasma and urinary testosterone response to one i.m. injection of 5,000 IU human chorionic gonadotropin (HCG) was tested in 45 children and adolescents of several diagnostic entities: testosterone was measured before the injection and on the second, fourth and sixth days thereafter. It was found that there was a better correlation between the testosterone concentrations and the different pubertal stages than between testosterone concentration and either chronological or skeletal age. In the children with normal pubertal development, there was a slight rise in basal testosterone concentration with the progression of the pubertal stages. HCG caused a rise in plasma and urinary testosterone: this response was more marked in pubertal stages 4 and 5. The urinary response was variable whereas the changes in plasma testosterone concentration were more constant. In children and adolescents with primary or secondary hypogonadism, the basal levels of testosterone were low or undetectable and there was only a slight response to the single dose of HCG. It was concluded that a single i.m. injection of 5,000 IU HCG and the determination of plasma testosterone before, and two and four days after injection is a useful screening test for Leydig cell function."} {"id": "PMID:1262203", "title": "High incidence of ventricular septal defects in a family.", "content": "A family is described in which eight children, belonging to two sibships, had ventricular septal defects. The diagnoses were based on the clinical, radiological and ECG findings. The findings are compatible with a multifactorial mode of inheritance carrying a recurrence risk of 25 to 50%.", "contents": "High incidence of ventricular septal defects in a family. A family is described in which eight children, belonging to two sibships, had ventricular septal defects. The diagnoses were based on the clinical, radiological and ECG findings. The findings are compatible with a multifactorial mode of inheritance carrying a recurrence risk of 25 to 50%."} {"id": "PMID:1262204", "title": "Osteochondroma following irradiation. Case report and review of the literature.", "content": "A case of an osteochondroma of the distal radius appearing 10 years after irradiation for hemangioma in infancy is described. The literature is reviewed and the effects of irradiation on bone growth, and possible malignant change, are discussed.", "contents": "Osteochondroma following irradiation. Case report and review of the literature. A case of an osteochondroma of the distal radius appearing 10 years after irradiation for hemangioma in infancy is described. The literature is reviewed and the effects of irradiation on bone growth, and possible malignant change, are discussed."} {"id": "PMID:1262205", "title": "Herpes simplex encephalitis simulating systemic embolism.", "content": "A case of herpes simplex virus encephalitis is described in a patient known to suffer from chronic atrial fibrillation and whose clinical symptoms suggested cerebral embolism of cardiac origin. The final diagnosis was based on the presence of herpes simplex virus type 1 antibodies in the cerebrospinal fluid and a significant rise in antibody titers in the serum. The patient regained consciousness after craniotomy and treatment with idoxuridine. The case emphasizes that the possibility of herpetic encephalitis should be considered in patients presenting with typical signs of a cerebrovascular accident.", "contents": "Herpes simplex encephalitis simulating systemic embolism. A case of herpes simplex virus encephalitis is described in a patient known to suffer from chronic atrial fibrillation and whose clinical symptoms suggested cerebral embolism of cardiac origin. The final diagnosis was based on the presence of herpes simplex virus type 1 antibodies in the cerebrospinal fluid and a significant rise in antibody titers in the serum. The patient regained consciousness after craniotomy and treatment with idoxuridine. The case emphasizes that the possibility of herpetic encephalitis should be considered in patients presenting with typical signs of a cerebrovascular accident."} {"id": "PMID:1262209", "title": "High-purity water supplies for biomedical research laboratories.", "content": "A quantitative bacteriological survey of high-purity water systems used in biomedical research laboratories at the National Institutes of Health revealed great variations among the systems. In general, distilled water had significantly lower contamination levels than deionized water. Interviews with investigators revealed their conceptions about the importance of bacterial contamination in high-purity water and some expectations about bacterial quality. Guidelines are suggested for the use of water from systems of varying quality.", "contents": "High-purity water supplies for biomedical research laboratories. A quantitative bacteriological survey of high-purity water systems used in biomedical research laboratories at the National Institutes of Health revealed great variations among the systems. In general, distilled water had significantly lower contamination levels than deionized water. Interviews with investigators revealed their conceptions about the importance of bacterial contamination in high-purity water and some expectations about bacterial quality. Guidelines are suggested for the use of water from systems of varying quality."} {"id": "PMID:1262210", "title": "A stable liquid human reference serum.", "content": "A procedure is described for the preparation of a liquid reference control suitable for use in calibration of both automated and manual chemical procedures. Pooled human serum was partially dehydrated under vacuum from the frozen state. Ethylene glycol was added to replace the water to produce a 30% solution. The stability of a liquid reference control so prepared was investigated by examining aliquots stored at room, refrigerator, and freezer temperatures for various storage times up to 568 days. Eighteen components were assayed with the Technicon Auto Analyzers SMA 6/60 and 12/60 in a tandem mode with creatinine and creatine phosphokinase channels replacing the glucose and urea nitrogen of the standard SMA 12/60. Initially specimens were examined daily, then at weekly, monthly, and longer intervals. Standard deviations and coefficients of variation were compared with those obtained on commercial lyophilized controls assayed during the same time interval. The results indicated that the ethylene glycol treatment can be used to produce a liquid reference control with stabilized enzyme activities and stable component levels.", "contents": "A stable liquid human reference serum. A procedure is described for the preparation of a liquid reference control suitable for use in calibration of both automated and manual chemical procedures. Pooled human serum was partially dehydrated under vacuum from the frozen state. Ethylene glycol was added to replace the water to produce a 30% solution. The stability of a liquid reference control so prepared was investigated by examining aliquots stored at room, refrigerator, and freezer temperatures for various storage times up to 568 days. Eighteen components were assayed with the Technicon Auto Analyzers SMA 6/60 and 12/60 in a tandem mode with creatinine and creatine phosphokinase channels replacing the glucose and urea nitrogen of the standard SMA 12/60. Initially specimens were examined daily, then at weekly, monthly, and longer intervals. Standard deviations and coefficients of variation were compared with those obtained on commercial lyophilized controls assayed during the same time interval. The results indicated that the ethylene glycol treatment can be used to produce a liquid reference control with stabilized enzyme activities and stable component levels."} {"id": "PMID:1262211", "title": "Evaluation of tests for infectious mononucleosis through proficiency testing.", "content": "Two standard tests for infectious mononucleosis (the Davidsohn differential and the ox cell hemolysin test) and ten slide tests; Monotest (Wampole), Monospot (Ortho), IM Kit (Micro. Res. Corp.) Monosticon (Organon), Diagluto IM (Beckman), Monosticon Dri-Dot (Organon), Bacto-Hetrol (Difco), Mono-Diff (Wampole), Monophile (Bio-Diagnostic Systems) and Rythrotox (BMC) were evaluated as they were used in 50 laboratories within the State of Utah and by two referee laboratories outside the state. The state proficiency testing program for infectious mononucleosis was modified so that the desired evaluation survey data could be obtained. Sensitivity, specificity, reproducibility (within and between shipments) and percent agreement with target results were determined for each test; factors which might have affected the test results were evaluated to determine which were correlated with good performance.", "contents": "Evaluation of tests for infectious mononucleosis through proficiency testing. Two standard tests for infectious mononucleosis (the Davidsohn differential and the ox cell hemolysin test) and ten slide tests; Monotest (Wampole), Monospot (Ortho), IM Kit (Micro. Res. Corp.) Monosticon (Organon), Diagluto IM (Beckman), Monosticon Dri-Dot (Organon), Bacto-Hetrol (Difco), Mono-Diff (Wampole), Monophile (Bio-Diagnostic Systems) and Rythrotox (BMC) were evaluated as they were used in 50 laboratories within the State of Utah and by two referee laboratories outside the state. The state proficiency testing program for infectious mononucleosis was modified so that the desired evaluation survey data could be obtained. Sensitivity, specificity, reproducibility (within and between shipments) and percent agreement with target results were determined for each test; factors which might have affected the test results were evaluated to determine which were correlated with good performance."} {"id": "PMID:1262245", "title": "Hepatoencephalopathy associated with situs inversus of abdominal organs and vascular anomalies in a dog.", "content": "Throughout its life, a 1-year-old Doberman Pinscher dog had had gastrointestinal disorders and episodes of circling. It was less active than its littermates, and it usually seemed lethargic. When 3 months old, the pup had been anesthetized for ear cropping and it had remained anesthetized for 32 hours. Behavioral problems were apparent when the dog was 11 months old. Two weeks later the behavioral problems accentuated to the point that the dog developed \"temper tantrums\" and became aggressive toward its owner. On the basis of clinicopathologic and contrast radiographic findings, hepatoencephalopathy due to persistent patent ductus venosus was diagnosed and the dog was euthanatized. Situs inversus abdominalis and multiple vascular anomalies were found at necropsy. Gross and microscopic studies of the viscera were correlated with corrosion casts of the vasculature. In addition to changes in organ position, 3 spleens and malformation of the pancreas were observed. Vascular anomalies were: (1) The portal vein was contiguous with the common hepatic vein by way of a patent ductus venosus; branches of the portal vein were not given off to the liver; (2) the caudal vena cava was continued by the azygos vein, and a cranial segment of the caudal vena cava was absent; (3) the hepatic artery was larger than normal; (4) the left gastric artery arose anomalously from the cranial mesenteric artery; and (5) histologic and radiographic study of the liver did not reveal any interlobular branches of the portal vein; however, hypoplastic branches of the gastroduodenal vein did enter the liver and were demonstrated on a corrosion cast.", "contents": "Hepatoencephalopathy associated with situs inversus of abdominal organs and vascular anomalies in a dog. Throughout its life, a 1-year-old Doberman Pinscher dog had had gastrointestinal disorders and episodes of circling. It was less active than its littermates, and it usually seemed lethargic. When 3 months old, the pup had been anesthetized for ear cropping and it had remained anesthetized for 32 hours. Behavioral problems were apparent when the dog was 11 months old. Two weeks later the behavioral problems accentuated to the point that the dog developed \"temper tantrums\" and became aggressive toward its owner. On the basis of clinicopathologic and contrast radiographic findings, hepatoencephalopathy due to persistent patent ductus venosus was diagnosed and the dog was euthanatized. Situs inversus abdominalis and multiple vascular anomalies were found at necropsy. Gross and microscopic studies of the viscera were correlated with corrosion casts of the vasculature. In addition to changes in organ position, 3 spleens and malformation of the pancreas were observed. Vascular anomalies were: (1) The portal vein was contiguous with the common hepatic vein by way of a patent ductus venosus; branches of the portal vein were not given off to the liver; (2) the caudal vena cava was continued by the azygos vein, and a cranial segment of the caudal vena cava was absent; (3) the hepatic artery was larger than normal; (4) the left gastric artery arose anomalously from the cranial mesenteric artery; and (5) histologic and radiographic study of the liver did not reveal any interlobular branches of the portal vein; however, hypoplastic branches of the gastroduodenal vein did enter the liver and were demonstrated on a corrosion cast."} {"id": "PMID:1262247", "title": "Primary hyperparathyroidism in a dog.", "content": "Anorexia, severe skeletal demineralization, and muscular weaknesss developed in a 9 year-old Collie. Hypercalcemia, hypophosphatemia, and nephrocalcinosis were found on clinical evaluation. The surgical removal of a parathyroid adenoma was followed by profound hypocalcemia that was unresponsive to calcium therapy, and the dog died. The persistent hypocalcemia was attributed to increased deposition of calcium in mineral-deficient bone.", "contents": "Primary hyperparathyroidism in a dog. Anorexia, severe skeletal demineralization, and muscular weaknesss developed in a 9 year-old Collie. Hypercalcemia, hypophosphatemia, and nephrocalcinosis were found on clinical evaluation. The surgical removal of a parathyroid adenoma was followed by profound hypocalcemia that was unresponsive to calcium therapy, and the dog died. The persistent hypocalcemia was attributed to increased deposition of calcium in mineral-deficient bone."} {"id": "PMID:1262248", "title": "Diagnostic abdominal paracentesis and lavage: experimental and clinical evaluations in the dog.", "content": "Diagnostic abdominal paracentesis and saline lavage, using a peritoneal dialysis catheter, was evaluated experimentally and clinically in dogs. Use of the catheter enabled detection of abdominal fluid in volumes as low as 0.2 ml/kg of body weight. In paracentesis, the catheter proved to be a more reliable means of detecting hemoperitoneum than did a needle. In 14 clinical cases of blunt trauma, use of the catheter provided reliable evidence of intraabdominal injury.", "contents": "Diagnostic abdominal paracentesis and lavage: experimental and clinical evaluations in the dog. Diagnostic abdominal paracentesis and saline lavage, using a peritoneal dialysis catheter, was evaluated experimentally and clinically in dogs. Use of the catheter enabled detection of abdominal fluid in volumes as low as 0.2 ml/kg of body weight. In paracentesis, the catheter proved to be a more reliable means of detecting hemoperitoneum than did a needle. In 14 clinical cases of blunt trauma, use of the catheter provided reliable evidence of intraabdominal injury."} {"id": "PMID:1262249", "title": "Diagnostic abdominal paracentesis and lavage in the evaluation of abdominal injuries in dogs and cats: clinical and experimental investigations.", "content": "Abdominal paracentesis and lavage, using a peritoneal dialysis catheter, was evaluated clinically for use in detecting intraabdominal injury in 20 dogs and 3 cats. The technique was also evaluated experimentally in 12 dogs in which various volumes of autogenous blood were infused into the abdomen. The procedure was found to be safe, well tolerated, and reliable in the detection of intraabdominal injuries. The volume of free blood in the abdomen of the experimental dogs was accurately determined. The procedure was superior to physical examination and to needle paracentesis for the early detection and evaluation of intraabdominal injuries.", "contents": "Diagnostic abdominal paracentesis and lavage in the evaluation of abdominal injuries in dogs and cats: clinical and experimental investigations. Abdominal paracentesis and lavage, using a peritoneal dialysis catheter, was evaluated clinically for use in detecting intraabdominal injury in 20 dogs and 3 cats. The technique was also evaluated experimentally in 12 dogs in which various volumes of autogenous blood were infused into the abdomen. The procedure was found to be safe, well tolerated, and reliable in the detection of intraabdominal injuries. The volume of free blood in the abdomen of the experimental dogs was accurately determined. The procedure was superior to physical examination and to needle paracentesis for the early detection and evaluation of intraabdominal injuries."} {"id": "PMID:1262251", "title": "Idiopathic hypoparathyroidism in a dog.", "content": "Idiopathic hypoparathyroidism in a 3-year-old dog was manifested clinically as periodic episodes of depression, vomiting, and tetanic convulsions. Hypocalcemia and hyperphosphatemia were detected late in the course of the illness, but the dog died before corrective measures could be instituted. The pathologic features were similar to those reported in dogs in which hypoparathyroidism was induced by injection of homologous parathyroid tissue, thus suggesting an auto-immune pathogenesis.", "contents": "Idiopathic hypoparathyroidism in a dog. Idiopathic hypoparathyroidism in a 3-year-old dog was manifested clinically as periodic episodes of depression, vomiting, and tetanic convulsions. Hypocalcemia and hyperphosphatemia were detected late in the course of the illness, but the dog died before corrective measures could be instituted. The pathologic features were similar to those reported in dogs in which hypoparathyroidism was induced by injection of homologous parathyroid tissue, thus suggesting an auto-immune pathogenesis."} {"id": "PMID:1262253", "title": "Antimetabolites produced by microorganisms. XV Synthesis of 2-methyl-L-arginine, 2-methyl-L-ornithine and their enantiomers.", "content": "5-(3-Azidopropyl)-5-methyl-2, 4-imidazolidinedione was prepared either from 5-(3-chloropropyl)-5-methyl-2,4-imidazolidinedione or 5-methyl-5-(3-[(4-methylphenyl)sulfonyloxy]-propyl)-5-methyl-2, 4-imidazolidinedione and hydrogenolyzed to the corresponding amine which, after carbamimidoylation, afforded 2-methyl-DL-arginine upon acid hydrolysis. Racemic 2-methylarginine was converted enzymically to a mixture of 2-methyl-D-arginine and 2-methyl-L-ornithine. 2-Methyl-L-arginine was reconstructed from 2-methyl-L-ornithine via its Cu(II) chelate with O-methyl-isourea and 2-methyl-D-ornithine was obtained by alkaline hydrolysis of 2-methyl-D-arginine.", "contents": "Antimetabolites produced by microorganisms. XV Synthesis of 2-methyl-L-arginine, 2-methyl-L-ornithine and their enantiomers. 5-(3-Azidopropyl)-5-methyl-2, 4-imidazolidinedione was prepared either from 5-(3-chloropropyl)-5-methyl-2,4-imidazolidinedione or 5-methyl-5-(3-[(4-methylphenyl)sulfonyloxy]-propyl)-5-methyl-2, 4-imidazolidinedione and hydrogenolyzed to the corresponding amine which, after carbamimidoylation, afforded 2-methyl-DL-arginine upon acid hydrolysis. Racemic 2-methylarginine was converted enzymically to a mixture of 2-methyl-D-arginine and 2-methyl-L-ornithine. 2-Methyl-L-arginine was reconstructed from 2-methyl-L-ornithine via its Cu(II) chelate with O-methyl-isourea and 2-methyl-D-ornithine was obtained by alkaline hydrolysis of 2-methyl-D-arginine."} {"id": "PMID:1262254", "title": "Antitumor activity of derivatives of mycophenolic acid.", "content": "One hundred and eight derivatives of mycophenolic acid (MA) have been prepared by modifications at the phenolic hydroxyl and/or carboxyl sites. None of these compounds was as effective as MA in suppressing cell growth of L-518Y cell in vitro, whereas several compounds with changes at both the hydroxyl and carboxyl groups were more effective than MA against Ehrlich solid carcinoma and L-1210 leukemia in mice.", "contents": "Antitumor activity of derivatives of mycophenolic acid. One hundred and eight derivatives of mycophenolic acid (MA) have been prepared by modifications at the phenolic hydroxyl and/or carboxyl sites. None of these compounds was as effective as MA in suppressing cell growth of L-518Y cell in vitro, whereas several compounds with changes at both the hydroxyl and carboxyl groups were more effective than MA against Ehrlich solid carcinoma and L-1210 leukemia in mice."} {"id": "PMID:1262255", "title": "Carbamoyl mycophenolic acid ethylester, an oral antitumor agent.", "content": "Several derivatives of mycophenolic acid (MA) were tested for their antitumor activity against leukemia L-1210 when administered orally and carbamoyl mycophenolic acid ethylester (CMAE) was selected as the most active antitumor agent in these tests. An oral administration of CMAE also inhibited the growth of Ehrlich solid carcinoma, NF sarcoma, myeloma X-5563 and sarcoma 180 in mice. In comparison with antitumor activity of MA, the improvement in activity of CMAE against leukemia L-1210 and Ehrlich solid carcinoma was indeed remarkable, CMAE seems to be less immunosuppressive than MA.", "contents": "Carbamoyl mycophenolic acid ethylester, an oral antitumor agent. Several derivatives of mycophenolic acid (MA) were tested for their antitumor activity against leukemia L-1210 when administered orally and carbamoyl mycophenolic acid ethylester (CMAE) was selected as the most active antitumor agent in these tests. An oral administration of CMAE also inhibited the growth of Ehrlich solid carcinoma, NF sarcoma, myeloma X-5563 and sarcoma 180 in mice. In comparison with antitumor activity of MA, the improvement in activity of CMAE against leukemia L-1210 and Ehrlich solid carcinoma was indeed remarkable, CMAE seems to be less immunosuppressive than MA."} {"id": "PMID:1262256", "title": "Inhibition of the initial dipeptide synthesis of globin chains by the antibiotic enomycin in the reticulocyte lysate.", "content": "During inhibition of protein synthesis by the antibiotic enomycin at less than 5nm in the reticulocyte lysate system, polyribosomes disaggregated and the 80S ribosomes accumulated. At these concentrations little inhibition of chain elongation and release from the ribosomes was demonstrated. Enomycin caused an increase in the amount of 80S initiation complex as well as the 40S ribosomal subunit-Met-tRNA complex. The former complex could react with puromycin under the inhibiting conditions. Val-tRNA binding to the 80S ribosomes was not decreased by the antibiotic. However pactamycin-induced accumulation of the initial dipeptide (fMet-Val) was inhibited when the system was preincubated with enomycin and and fMet-tRnaf. Thus the preferential inhibition of the initial phase of protein synthesis by enomycin is made evident by its inhibition of the initial dipeptide synthesis.", "contents": "Inhibition of the initial dipeptide synthesis of globin chains by the antibiotic enomycin in the reticulocyte lysate. During inhibition of protein synthesis by the antibiotic enomycin at less than 5nm in the reticulocyte lysate system, polyribosomes disaggregated and the 80S ribosomes accumulated. At these concentrations little inhibition of chain elongation and release from the ribosomes was demonstrated. Enomycin caused an increase in the amount of 80S initiation complex as well as the 40S ribosomal subunit-Met-tRNA complex. The former complex could react with puromycin under the inhibiting conditions. Val-tRNA binding to the 80S ribosomes was not decreased by the antibiotic. However pactamycin-induced accumulation of the initial dipeptide (fMet-Val) was inhibited when the system was preincubated with enomycin and and fMet-tRnaf. Thus the preferential inhibition of the initial phase of protein synthesis by enomycin is made evident by its inhibition of the initial dipeptide synthesis."} {"id": "PMID:1262301", "title": "Evidence for diverse types of large plasmids in tumor-inducing strains of Agrobacterium.", "content": "Homology between the large plasmids of 15 pathogenic Agrobacterium strains isolated from various parts of the world has been measured and was found to vary over a wide range, from 3 to 100%. Two genetically distinct groups of plasmids can be identified: one closely related to the plasmid of A. tumefaciens A6, an octopine-utilizing strain, and the other closely related to the plasmid of A. tumefaciens C-58, a nopaline-utilizing strain. The plasmids of four Agrobacterium strains do not belong to either group. One of these four strains utilizes octopine, one utilizes nopaline, and two utilize neither. Three strains contained two large plasmids. In one of these strains, the two plasmids were not homologous to one another. Chromosomal homologies for the Agrobacterium strains surveyed also vary over a wide range, but do not correlate with plasmid homologies. Neither do plasmid homologies correlate with any numerical classification scheme. The significance of these plasmid homology studies for crown gall tumorigenesis is considered.", "contents": "Evidence for diverse types of large plasmids in tumor-inducing strains of Agrobacterium. Homology between the large plasmids of 15 pathogenic Agrobacterium strains isolated from various parts of the world has been measured and was found to vary over a wide range, from 3 to 100%. Two genetically distinct groups of plasmids can be identified: one closely related to the plasmid of A. tumefaciens A6, an octopine-utilizing strain, and the other closely related to the plasmid of A. tumefaciens C-58, a nopaline-utilizing strain. The plasmids of four Agrobacterium strains do not belong to either group. One of these four strains utilizes octopine, one utilizes nopaline, and two utilize neither. Three strains contained two large plasmids. In one of these strains, the two plasmids were not homologous to one another. Chromosomal homologies for the Agrobacterium strains surveyed also vary over a wide range, but do not correlate with plasmid homologies. Neither do plasmid homologies correlate with any numerical classification scheme. The significance of these plasmid homology studies for crown gall tumorigenesis is considered."} {"id": "PMID:1262302", "title": "Distribution of peptidoglycan synthetase activities between sporangia and forespores in sporulating cells of Bacillus sphaericus.", "content": "Sporulating cells of Bacillus sphaericus 9602 containing fully engulfed forespores at different stages of maturity were broken by ultrasonic disruption, followed by grinding with alumina. In this way soluble enzymes derived mainly from the sporangial or from the forespore cytoplasms were obtained. Diaminopimelate ligase activity is required exclusively for cortical peptidoglycan synthesis, is absent during vegetative growth, and is synthesized during forespore maturation. It is found exclusively in the sporangial cytoplasm. L-lysine ligase is required for vegetative cell wall peptidoglycan synthesis but not for cortex synthesis. It is found in both fractions, but it has a fourfold higher specific activity in the forespore cytoplasm. Other enzymes that are required for synthesis of the nucleotide-pentapeptide precursors of both cortical and vegetative cell wall peptidoglycans are found in similar specific activities in both compartments. Mature spores, free of any residual sporangial material, have specific activities of all of these enzymes and of L-lysine ligase similar to those in forespores and in vegetative cells and are devoid of diaminopimelate ligase activity. Thus, the differential expression of at least one gene required for spore cortex synthesis in B. sphaericus occurs exclusively in the sporangial cytoplasm.", "contents": "Distribution of peptidoglycan synthetase activities between sporangia and forespores in sporulating cells of Bacillus sphaericus. Sporulating cells of Bacillus sphaericus 9602 containing fully engulfed forespores at different stages of maturity were broken by ultrasonic disruption, followed by grinding with alumina. In this way soluble enzymes derived mainly from the sporangial or from the forespore cytoplasms were obtained. Diaminopimelate ligase activity is required exclusively for cortical peptidoglycan synthesis, is absent during vegetative growth, and is synthesized during forespore maturation. It is found exclusively in the sporangial cytoplasm. L-lysine ligase is required for vegetative cell wall peptidoglycan synthesis but not for cortex synthesis. It is found in both fractions, but it has a fourfold higher specific activity in the forespore cytoplasm. Other enzymes that are required for synthesis of the nucleotide-pentapeptide precursors of both cortical and vegetative cell wall peptidoglycans are found in similar specific activities in both compartments. Mature spores, free of any residual sporangial material, have specific activities of all of these enzymes and of L-lysine ligase similar to those in forespores and in vegetative cells and are devoid of diaminopimelate ligase activity. Thus, the differential expression of at least one gene required for spore cortex synthesis in B. sphaericus occurs exclusively in the sporangial cytoplasm."} {"id": "PMID:1262303", "title": "Nitrate reductase activity in heme-deficient mutants of Staphylococcus aureus.", "content": "Mutants H-14 and H-18 of Staphylococcus aureus require hemin for growth on glycerol and other nonfermentable substrates. H-14 also responds to delta-aminolevulinate. Heme-deficient cells grown in the presence of nitrate do not have lactate-nitrate reductase activity but gain this activity when incubated with hemin in buffer and glucose. Lactate-nitrate reductase activity is also restored to the membrane fraction from such cells by incubation with hemin and dithiothreitol; addition of adenosine 5'-triphosphate has no effect upon the restoration. Cells grown with nitrate in the absence of hemin have two to five times more reduced benzyl viologen-nitrate reductase activity than do those grown with hemin. The activity increases throughout the growth period in the absence of hemin, but with hemin present enzyme formation ceases before the end of growth. There was no evidence of enzyme destruction. The distribution of nitrate reductase activity between membrane and cytoplasm was similar in cells grown with and without hemin; 70 to 90% was in the cytoplasm. It is concluded that heme-deficient staphylococci form apo-cytochrome b, which readily combines in vitro with its prosthetic group to restore normal function. The avaliability of the heme prosthetic group influences the formation of nitrate reductase.", "contents": "Nitrate reductase activity in heme-deficient mutants of Staphylococcus aureus. Mutants H-14 and H-18 of Staphylococcus aureus require hemin for growth on glycerol and other nonfermentable substrates. H-14 also responds to delta-aminolevulinate. Heme-deficient cells grown in the presence of nitrate do not have lactate-nitrate reductase activity but gain this activity when incubated with hemin in buffer and glucose. Lactate-nitrate reductase activity is also restored to the membrane fraction from such cells by incubation with hemin and dithiothreitol; addition of adenosine 5'-triphosphate has no effect upon the restoration. Cells grown with nitrate in the absence of hemin have two to five times more reduced benzyl viologen-nitrate reductase activity than do those grown with hemin. The activity increases throughout the growth period in the absence of hemin, but with hemin present enzyme formation ceases before the end of growth. There was no evidence of enzyme destruction. The distribution of nitrate reductase activity between membrane and cytoplasm was similar in cells grown with and without hemin; 70 to 90% was in the cytoplasm. It is concluded that heme-deficient staphylococci form apo-cytochrome b, which readily combines in vitro with its prosthetic group to restore normal function. The avaliability of the heme prosthetic group influences the formation of nitrate reductase."} {"id": "PMID:1262304", "title": "Measurement of growth and iron deposition in Sphaerotilus discophorus.", "content": "Aspects of the physiology of iron deposition of an iron-precipitating strain of Sphaerotilus were investigated in laboratory culture to characterize the process. Measurement of growth (incorporated L-[3H]alanine) and iron deposition (incorporated 59Fe) demonstrated that Sphaerotilus exhibit a characteristic temporal pattern of iron deposition, which is delayed until the latter portion of the exponential or the onset of the stationary growth phase. The growth rate (mu=0.17 h-1) was apparently independent of the iron concentration in the medium. There was, furthermore, no direct correlation between the iron concentration and final cell protein yield. It was concluded from experiments involving growth on artificial substrata (glass cover slips) that sessile populations derived no phsiological advantage (manifested as differences in growth rates) over free-living cells. There was no difference in the rate or onset of iron deposition of attached compared to suspended cells. Blocking of protein synthesis by the addition of chloramphenicol suggested that, once iron deposition was initiated, continued protein synthesis was not required for full expression of this capability. The results suggested that iron deposition may be possibly mediated by certain of the constituents of the organism's sheath.", "contents": "Measurement of growth and iron deposition in Sphaerotilus discophorus. Aspects of the physiology of iron deposition of an iron-precipitating strain of Sphaerotilus were investigated in laboratory culture to characterize the process. Measurement of growth (incorporated L-[3H]alanine) and iron deposition (incorporated 59Fe) demonstrated that Sphaerotilus exhibit a characteristic temporal pattern of iron deposition, which is delayed until the latter portion of the exponential or the onset of the stationary growth phase. The growth rate (mu=0.17 h-1) was apparently independent of the iron concentration in the medium. There was, furthermore, no direct correlation between the iron concentration and final cell protein yield. It was concluded from experiments involving growth on artificial substrata (glass cover slips) that sessile populations derived no phsiological advantage (manifested as differences in growth rates) over free-living cells. There was no difference in the rate or onset of iron deposition of attached compared to suspended cells. Blocking of protein synthesis by the addition of chloramphenicol suggested that, once iron deposition was initiated, continued protein synthesis was not required for full expression of this capability. The results suggested that iron deposition may be possibly mediated by certain of the constituents of the organism's sheath."} {"id": "PMID:1262305", "title": "Constitutive synthesis of enzymes of the protocatechuate pathway and of the beta-ketoadipate uptake system in mutant strains of Pseudomonas putida.", "content": "Mutant Pseudomonas putida strains that produce constitutive levels of the beta-ketoadipate uptake system are selected by the sequential transfer of cultures between mineral growth media supplemented with the noninducing growth substrate succinate and growth media containing beta-ketoadipate as the sole carbon and energy source. The mutant strains also produce constitutively three catabolic enzymes that give rise to beta-ketoadipate from the metabolic precursor beta-carboxy-cis, cis-muconate, and thus a single regulatory gene appears to govern the expression of the enzymes as well as the uptake system. The three enzymes that convert beta-carboxy-cis, cis-muconate to beta-ketoadipate are induced to higher levels when the orgainisms are grown with p-hydroxybenzoate (a compound that is catabolized via beta-ketoadipate); the beta-ketoadipate uptake system is partially repressed when the cells are grwon at the expense of p-hydroxybenzoate. The transferase that acts upon beta-ketoadipate remains inducible in the constitutive mutant strains. Thus a minimum of three biosynthetic controls must be exerted over the expression of the five genes. Since the regulatory mutation does not alter the expression of the gene for the transferase, the physiological target of the selection procedure appears to be mutant strains that produce the uptake system constitutively. Levels of the uptake system are higher in uninduced constitutive mutant cultures than in induced cultures of the wild type. Hence procedures analogous to the one we employed may be of general use in obtaining mutant strains that produce high levels of uptake systems.", "contents": "Constitutive synthesis of enzymes of the protocatechuate pathway and of the beta-ketoadipate uptake system in mutant strains of Pseudomonas putida. Mutant Pseudomonas putida strains that produce constitutive levels of the beta-ketoadipate uptake system are selected by the sequential transfer of cultures between mineral growth media supplemented with the noninducing growth substrate succinate and growth media containing beta-ketoadipate as the sole carbon and energy source. The mutant strains also produce constitutively three catabolic enzymes that give rise to beta-ketoadipate from the metabolic precursor beta-carboxy-cis, cis-muconate, and thus a single regulatory gene appears to govern the expression of the enzymes as well as the uptake system. The three enzymes that convert beta-carboxy-cis, cis-muconate to beta-ketoadipate are induced to higher levels when the orgainisms are grown with p-hydroxybenzoate (a compound that is catabolized via beta-ketoadipate); the beta-ketoadipate uptake system is partially repressed when the cells are grwon at the expense of p-hydroxybenzoate. The transferase that acts upon beta-ketoadipate remains inducible in the constitutive mutant strains. Thus a minimum of three biosynthetic controls must be exerted over the expression of the five genes. Since the regulatory mutation does not alter the expression of the gene for the transferase, the physiological target of the selection procedure appears to be mutant strains that produce the uptake system constitutively. Levels of the uptake system are higher in uninduced constitutive mutant cultures than in induced cultures of the wild type. Hence procedures analogous to the one we employed may be of general use in obtaining mutant strains that produce high levels of uptake systems."} {"id": "PMID:1262306", "title": "Role of arginine deiminase in growth of Mycoplasma hominis.", "content": "Arginine has been considered as the major energy source of nonglycolytic arginine-utilizing mycoplasmata. When three strains of Mycoplasma arginini, and one strain each of Mycoplasma arthritidis, Mycoplasma fermentans, Mycoplasma gallinarum, Mycoplasma gallisepticum and Mycoplasma hominis were grown in the medium with high arginine concentration (34 mM) compared with low arginine (4 mM), both the protein content of the organisms and the specific activity of arginine deiminase increased. M. fermentans, the one arginine-utilizing species included in the survey which is also glycolytic, showed an increase in protein content but no increase in specific activity of the enzyme. The glycolytic non-arginine-utilizing M. gallisepticum did not show an increase in either parameter. The Km for arginine deiminase from crude cell extracts was 1.66 X 10(-4)M. The enzyme demonstrated a hyperbolic activation curve subject to substrate inhibition and was not affected by the presence of L-histidine. When mycoplasmic protein and arginine deiminase were determined for M. hominis under aerobic and anaerobic conditions, aerobically grown cells exhibited no detectable enzymatic increases until late in log phase. Higher levels of arginine deiminase were observed earlier in the anaerobic growth cycle. The rate of 14CO2 evolution from [guanido-14C]arginine was not altered in arginine-supplemented cells compared with cells grown in low arginine. In addition, CO2 production did not parallel increased arginine deiminase activity. These observations argue that arginine is used only as an alternate energy source in these organisms.", "contents": "Role of arginine deiminase in growth of Mycoplasma hominis. Arginine has been considered as the major energy source of nonglycolytic arginine-utilizing mycoplasmata. When three strains of Mycoplasma arginini, and one strain each of Mycoplasma arthritidis, Mycoplasma fermentans, Mycoplasma gallinarum, Mycoplasma gallisepticum and Mycoplasma hominis were grown in the medium with high arginine concentration (34 mM) compared with low arginine (4 mM), both the protein content of the organisms and the specific activity of arginine deiminase increased. M. fermentans, the one arginine-utilizing species included in the survey which is also glycolytic, showed an increase in protein content but no increase in specific activity of the enzyme. The glycolytic non-arginine-utilizing M. gallisepticum did not show an increase in either parameter. The Km for arginine deiminase from crude cell extracts was 1.66 X 10(-4)M. The enzyme demonstrated a hyperbolic activation curve subject to substrate inhibition and was not affected by the presence of L-histidine. When mycoplasmic protein and arginine deiminase were determined for M. hominis under aerobic and anaerobic conditions, aerobically grown cells exhibited no detectable enzymatic increases until late in log phase. Higher levels of arginine deiminase were observed earlier in the anaerobic growth cycle. The rate of 14CO2 evolution from [guanido-14C]arginine was not altered in arginine-supplemented cells compared with cells grown in low arginine. In addition, CO2 production did not parallel increased arginine deiminase activity. These observations argue that arginine is used only as an alternate energy source in these organisms."} {"id": "PMID:1262307", "title": "Characteristics of Bacillus stearothermophilus mutants blocked in catabolic function.", "content": "With polyacrylamide disc gel electrophoresis and specific staining, it was demonstrated that one mutation involving the alcohol dehydrogenase of a double mutant of Bacillus stearothermophilus 1503 apparently prevented enzyme synthesis, and another lesion in the same organism resulted in synthesis of an inactive form of aconitase. Some properties of the double mutant and two fumarase mutants are discussed in relation to similar mutants derived from Bacillus subtilis.", "contents": "Characteristics of Bacillus stearothermophilus mutants blocked in catabolic function. With polyacrylamide disc gel electrophoresis and specific staining, it was demonstrated that one mutation involving the alcohol dehydrogenase of a double mutant of Bacillus stearothermophilus 1503 apparently prevented enzyme synthesis, and another lesion in the same organism resulted in synthesis of an inactive form of aconitase. Some properties of the double mutant and two fumarase mutants are discussed in relation to similar mutants derived from Bacillus subtilis."} {"id": "PMID:1262308", "title": "Formation of indole-3-carboxylic acid by Chromobacterium violaceum.", "content": "l-Tryptophan is converted to indole-3-carboxylic acid by growing cultures and resting cell suspensions of Chromobacterium violaceum", "contents": "Formation of indole-3-carboxylic acid by Chromobacterium violaceum. l-Tryptophan is converted to indole-3-carboxylic acid by growing cultures and resting cell suspensions of Chromobacterium violaceum"} {"id": "PMID:1262309", "title": "Evidence for autogenous regulation of Pseudomonas putida tryptophan synthase.", "content": "Studies of a trpA mutant constitutive for tryptophan synthase production support the hypothesis of autogenous regulation (R. F. Goldberger, 1974; A. R. Proctor and I. P. Crawford, 1975) of the Pseudomonas putida trpAB loci.", "contents": "Evidence for autogenous regulation of Pseudomonas putida tryptophan synthase. Studies of a trpA mutant constitutive for tryptophan synthase production support the hypothesis of autogenous regulation (R. F. Goldberger, 1974; A. R. Proctor and I. P. Crawford, 1975) of the Pseudomonas putida trpAB loci."} {"id": "PMID:1262310", "title": "Evidence that the isomerization of D-ribose and L-rhamnose is catalyzed by the same enzyme in Mycobacterium smegmatis.", "content": "D-Ribose isomerase was purified and crystallized from cells of Mycobacterium smegmatis grown on either D-ribose or L-rhamnose. Isomerase activity for both of these sugars remained together throughout the purification. The isomerase from L-rhamnose-grown cells had the same chemical and physical properties as the enzyme isolated from D-ribose grown cells. In addition, immunological studies indicated that both activities were in the same protein since antisera prepared against either of the crystals cross-reacted with the other and gave lines of symmetry by the agar gel diffusion method.", "contents": "Evidence that the isomerization of D-ribose and L-rhamnose is catalyzed by the same enzyme in Mycobacterium smegmatis. D-Ribose isomerase was purified and crystallized from cells of Mycobacterium smegmatis grown on either D-ribose or L-rhamnose. Isomerase activity for both of these sugars remained together throughout the purification. The isomerase from L-rhamnose-grown cells had the same chemical and physical properties as the enzyme isolated from D-ribose grown cells. In addition, immunological studies indicated that both activities were in the same protein since antisera prepared against either of the crystals cross-reacted with the other and gave lines of symmetry by the agar gel diffusion method."} {"id": "PMID:1262311", "title": "Regulation of L-phenylalanine ammonia-lyase from Rhizoctonia solani.", "content": "Maximal levels of L-henylalanine ammonia-lyase activity were observed when the mycelial felts of Rhizoctonia solani were grown for 4.5 days on Byrde synthetic medium containing 3.5% glucose and 0.3% L-phenylalanine, Differential centrifugation studies have indicated that the enzyme is localized in the soluble fraction. The time course of induction of L-phenylalanine ammonia-lyase activity by L-phenylalanine showed a lag period of 1 to 1.5 h and reached a maximum around 4 to 6 h after the addition of the inducer to the medium. L-Phenylalanine, L-tyrosine, and L-tryptophan were nearly equally efficient inducers of the enzyme. D-Phenylalanine was as efficient as the L-isomer, whereas D-tyrosine was a poor inducer. Light, gibberellic acid, indole 3-acetic acid, and kinetin had no effect on the induction of L-phenylalanine ammonia-lyase activity. Cycloheximide did not inhibit the uptake of amino acids by the mycelia but completely blocked the incorporation of radioactive amino acids into soluble proteins and the development of L-phenylalanine ammonia-lyase activity. Actinomycin D inhibited both the incorporation of 32P into ribonucleic acid and the enzyme activity. Conclusive evidence for de novo synthesis of L-phenylalanine ammonia-lyase was obtained by the incorporation of radioactive amino acids into the enzyme. Electrophoretic analysis of the purified preparation showed a single protein band that coincided with radioactivity and L-phenylalanine ammonia-lyase activity. Glucose and intermediates of the tricarboxylic acid cycle, like citric acid, alpha-ketoglutaric acid, and succinic acid, and the metabolites of L-phenylalanine, like o-coumaric acid, o-hydroxyphenylacetic acid, and protocatechuic acid, significantly repressed L-phenylalanine ammonia-lyase activity. The observed repression was not relieved by cyclic adenosine 5'-triphosphate.", "contents": "Regulation of L-phenylalanine ammonia-lyase from Rhizoctonia solani. Maximal levels of L-henylalanine ammonia-lyase activity were observed when the mycelial felts of Rhizoctonia solani were grown for 4.5 days on Byrde synthetic medium containing 3.5% glucose and 0.3% L-phenylalanine, Differential centrifugation studies have indicated that the enzyme is localized in the soluble fraction. The time course of induction of L-phenylalanine ammonia-lyase activity by L-phenylalanine showed a lag period of 1 to 1.5 h and reached a maximum around 4 to 6 h after the addition of the inducer to the medium. L-Phenylalanine, L-tyrosine, and L-tryptophan were nearly equally efficient inducers of the enzyme. D-Phenylalanine was as efficient as the L-isomer, whereas D-tyrosine was a poor inducer. Light, gibberellic acid, indole 3-acetic acid, and kinetin had no effect on the induction of L-phenylalanine ammonia-lyase activity. Cycloheximide did not inhibit the uptake of amino acids by the mycelia but completely blocked the incorporation of radioactive amino acids into soluble proteins and the development of L-phenylalanine ammonia-lyase activity. Actinomycin D inhibited both the incorporation of 32P into ribonucleic acid and the enzyme activity. Conclusive evidence for de novo synthesis of L-phenylalanine ammonia-lyase was obtained by the incorporation of radioactive amino acids into the enzyme. Electrophoretic analysis of the purified preparation showed a single protein band that coincided with radioactivity and L-phenylalanine ammonia-lyase activity. Glucose and intermediates of the tricarboxylic acid cycle, like citric acid, alpha-ketoglutaric acid, and succinic acid, and the metabolites of L-phenylalanine, like o-coumaric acid, o-hydroxyphenylacetic acid, and protocatechuic acid, significantly repressed L-phenylalanine ammonia-lyase activity. The observed repression was not relieved by cyclic adenosine 5'-triphosphate."} {"id": "PMID:1262312", "title": "Repair of ultraviolet light-induced damage in Micrococcus radiophilus, an extremely resistant microorganism.", "content": "Repair of ultraviolet radiation damage was examined in an extremely radioresistant organism, Micrococcus radiophilus. Measurement of the number of thymine-containing dimers formed as a function of ultraviolet dose suggests that the ability of this organism to withstand high doses of ultraviolet radiation (20,000 ergs/mm2) is not related to protective screening by pigments. M. radiophilus carries out a rapid excision of thymine dimers at doses of ultraviolet light up to 10,000 ergs/mm2. Synthesis of deoxyribonucleic acid is reduced after irradiation, but after removal of photodamage the rate approaches that in unirradiated cells. A comparison is drawn with Micrococcus luteus and M. radiodurans. We conclude that the extremely high resistance to ultraviolet irradiation in M. radiophilus is at least partly due to the presence of an efficient excision repair system.", "contents": "Repair of ultraviolet light-induced damage in Micrococcus radiophilus, an extremely resistant microorganism. Repair of ultraviolet radiation damage was examined in an extremely radioresistant organism, Micrococcus radiophilus. Measurement of the number of thymine-containing dimers formed as a function of ultraviolet dose suggests that the ability of this organism to withstand high doses of ultraviolet radiation (20,000 ergs/mm2) is not related to protective screening by pigments. M. radiophilus carries out a rapid excision of thymine dimers at doses of ultraviolet light up to 10,000 ergs/mm2. Synthesis of deoxyribonucleic acid is reduced after irradiation, but after removal of photodamage the rate approaches that in unirradiated cells. A comparison is drawn with Micrococcus luteus and M. radiodurans. We conclude that the extremely high resistance to ultraviolet irradiation in M. radiophilus is at least partly due to the presence of an efficient excision repair system."} {"id": "PMID:1262313", "title": "Map of genes for carotenoid and bacteriochlorophyll biosynthesis in Rhodopseudomonas capsulata.", "content": "The recently discovered gene transfer system of Rhodopseudomonas capsulata was used to construct a genetic map of a region concerned with bacteriochlorophyll and carotenoid production. Mutants blocked in the biosynthesis of these compounds were isolated, and each was characterized on the basis of pigments accumulated during growth under low pO2. One-point, two-point, three-point, and ratio test crosses were performed between various mutant strains, and the results were amenable to conventional genetic analyses. A mapping function was found that related cotransfer frequency to map distance. Seven clusters of mutations, five affecting carotenoid and two affecting bacteriochlorophyll biosynthesis, were arranged in one linkage group. Each cluster of mutations is thought to represent a gene. The length of the mapped region is estimated to be less than 1% of the genome. Cotransfer is observed between markers separated by about 5 to 10 genes.", "contents": "Map of genes for carotenoid and bacteriochlorophyll biosynthesis in Rhodopseudomonas capsulata. The recently discovered gene transfer system of Rhodopseudomonas capsulata was used to construct a genetic map of a region concerned with bacteriochlorophyll and carotenoid production. Mutants blocked in the biosynthesis of these compounds were isolated, and each was characterized on the basis of pigments accumulated during growth under low pO2. One-point, two-point, three-point, and ratio test crosses were performed between various mutant strains, and the results were amenable to conventional genetic analyses. A mapping function was found that related cotransfer frequency to map distance. Seven clusters of mutations, five affecting carotenoid and two affecting bacteriochlorophyll biosynthesis, were arranged in one linkage group. Each cluster of mutations is thought to represent a gene. The length of the mapped region is estimated to be less than 1% of the genome. Cotransfer is observed between markers separated by about 5 to 10 genes."} {"id": "PMID:1262314", "title": "Influence of exogenous sugars and polyols on C1-influx and efflux by the ascomycete Neocosmospora vasinfecta.", "content": "Glucose and other transportable sugars and polyols inhibited Cl- influx very soon after addition to mycelium in the process of Cl- accumulation. Under the usual experimental conditions (0.1 mM KCl, glucose greater than or equal to 2 mM) the mean percentage of inhibition of Cl- influx by glucose was 54.1 +/- 8.0 (+/- standard error; N = 26). Transport of the exogenous carbohydrate was necessary for inhibition of Cl- influx. Thus, the estimated Ki for glucose inhibition of Cl- influx (28 muM) was close to the Km for glucose transport; glycerol did not inhibit Cl- influx unless it was itself transported, and the degree of inhibition exerted by various carbohydrates correlated with their uptake rates. Inhibition was not caused by the accumulated sugar itself, as high levels (ca. 60 mM) of intramycelial 3-O-methylglucose gave rise to a stimulation of Cl- influx when the exogenous sugar was removed. It is suggested that interaction of Cl- and carbohydrate transport arises from competition for a common energy-coupling mechanism in the cell membrane. Both glucose and 3-O-methylglucose elicited Cl- efflux, but the maximal Cl- efflux rates were observed only after 40 min of incubation and only in the presence of the readily metabolizable glucose. Removal of the exogenous glucose, even after maximal Cl- efflux had been established, resulted in the rapid cessation of efflux. Studies under anaerobic conditions gave further evidence that glucose uptake was necessary and that efflux was not due to temporary depletion of energy reserves. It is proposed that glucose-induced leakage of Cl- is due to reversal of the Cl- uptake system, even though the Km for efflux is much greater than that for influx.", "contents": "Influence of exogenous sugars and polyols on C1-influx and efflux by the ascomycete Neocosmospora vasinfecta. Glucose and other transportable sugars and polyols inhibited Cl- influx very soon after addition to mycelium in the process of Cl- accumulation. Under the usual experimental conditions (0.1 mM KCl, glucose greater than or equal to 2 mM) the mean percentage of inhibition of Cl- influx by glucose was 54.1 +/- 8.0 (+/- standard error; N = 26). Transport of the exogenous carbohydrate was necessary for inhibition of Cl- influx. Thus, the estimated Ki for glucose inhibition of Cl- influx (28 muM) was close to the Km for glucose transport; glycerol did not inhibit Cl- influx unless it was itself transported, and the degree of inhibition exerted by various carbohydrates correlated with their uptake rates. Inhibition was not caused by the accumulated sugar itself, as high levels (ca. 60 mM) of intramycelial 3-O-methylglucose gave rise to a stimulation of Cl- influx when the exogenous sugar was removed. It is suggested that interaction of Cl- and carbohydrate transport arises from competition for a common energy-coupling mechanism in the cell membrane. Both glucose and 3-O-methylglucose elicited Cl- efflux, but the maximal Cl- efflux rates were observed only after 40 min of incubation and only in the presence of the readily metabolizable glucose. Removal of the exogenous glucose, even after maximal Cl- efflux had been established, resulted in the rapid cessation of efflux. Studies under anaerobic conditions gave further evidence that glucose uptake was necessary and that efflux was not due to temporary depletion of energy reserves. It is proposed that glucose-induced leakage of Cl- is due to reversal of the Cl- uptake system, even though the Km for efflux is much greater than that for influx."} {"id": "PMID:1262315", "title": "Purification and properties of chorismate mutase-prephenate dehydratase and prephenate dehydrogenase from Alcaligenes eutrophus.", "content": "Chorismate mutase and prephenate dehydratase from Alcaligenes autophus H16 were purified 470-fold with a yield of 24%. During the course of purification, including chromatography on diethylaminoethyl (DEAE)-cellulose, phenylalanine-substituted Sepharose, Sephadex G-200 and hydrogyapatite, both enzymes appeared in association. The ratio of their specific activities remained almost constant. The molecular weight of chorismate mutase-prephenast dehydratase varied from 144,000 to 187,000 due to the three different determination methods used. Treatment of electrophoretically homogeneous mutase-dehydratase with sodium dodecyl sulfate dissociated the enzyme into a single component of molecular weight 47,000, indicating a tetramer of identical subunits. The isoelectric point of the bifunctional enzyme was 5.8. Prephenate dehydrogenase was not associated with other enzyme activities; it was separated from mutasedehydratase by DEAE-cellulose chromatgraphy. Chromatography on DEAE Sephadex, Sephadex G-200, and hydroxyapatite resulted in a 740-fold purification with a yield of 10%. The molecular weight of the enzyme was 55,000 as determined by sucrose gradient centrifugation and 65,000 as determined by gel filtration or electrophoresis. Its isoelectric point was pH 6.6. In the overall conversion of chorismate to phenylpyruvate, free prephenate was formed which accumulated in the reaction mixture. The dissociation of prephenate allowed prephenate dehydrogenase to compete with prephenate dehydratase for the substrate.", "contents": "Purification and properties of chorismate mutase-prephenate dehydratase and prephenate dehydrogenase from Alcaligenes eutrophus. Chorismate mutase and prephenate dehydratase from Alcaligenes autophus H16 were purified 470-fold with a yield of 24%. During the course of purification, including chromatography on diethylaminoethyl (DEAE)-cellulose, phenylalanine-substituted Sepharose, Sephadex G-200 and hydrogyapatite, both enzymes appeared in association. The ratio of their specific activities remained almost constant. The molecular weight of chorismate mutase-prephenast dehydratase varied from 144,000 to 187,000 due to the three different determination methods used. Treatment of electrophoretically homogeneous mutase-dehydratase with sodium dodecyl sulfate dissociated the enzyme into a single component of molecular weight 47,000, indicating a tetramer of identical subunits. The isoelectric point of the bifunctional enzyme was 5.8. Prephenate dehydrogenase was not associated with other enzyme activities; it was separated from mutasedehydratase by DEAE-cellulose chromatgraphy. Chromatography on DEAE Sephadex, Sephadex G-200, and hydroxyapatite resulted in a 740-fold purification with a yield of 10%. The molecular weight of the enzyme was 55,000 as determined by sucrose gradient centrifugation and 65,000 as determined by gel filtration or electrophoresis. Its isoelectric point was pH 6.6. In the overall conversion of chorismate to phenylpyruvate, free prephenate was formed which accumulated in the reaction mixture. The dissociation of prephenate allowed prephenate dehydrogenase to compete with prephenate dehydratase for the substrate."} {"id": "PMID:1262316", "title": "Ammonia-sensitive mutant of Klebsiella aerogenes.", "content": "We have isolated a temperature-sensitive mutant of Klebsiella aerogenes unable to grow aerobically at 42 C in standard glucose minimal medium containing 0.03 M ammonium sulfate as a source of nitrogen. This strain, MK810, will grow at this temperature in significantly lower concentrations of ammonia (1 mM) or when ammonia is replaced by a growth rate-limiting source of nitrogen such as histidine or glutamate. A detailed physiological characterization and preliminary biochemical tests support the contention that the mutant has an altered alpha-ketoglutarate dehydrogenase that at the restrictive condition fails to manufacture sufficient succinyl-coenzyme A. We explain the ammonia sensitivity by the dual role of alpha-ketoglutarate as substrate for the formation of succinyl-coenzyme A and glutamate. A defect in the enzyme necessary for the production of succinyl-coenzyme A makes ammonia an overly effective competitor for alpha-ketoglutarate.", "contents": "Ammonia-sensitive mutant of Klebsiella aerogenes. We have isolated a temperature-sensitive mutant of Klebsiella aerogenes unable to grow aerobically at 42 C in standard glucose minimal medium containing 0.03 M ammonium sulfate as a source of nitrogen. This strain, MK810, will grow at this temperature in significantly lower concentrations of ammonia (1 mM) or when ammonia is replaced by a growth rate-limiting source of nitrogen such as histidine or glutamate. A detailed physiological characterization and preliminary biochemical tests support the contention that the mutant has an altered alpha-ketoglutarate dehydrogenase that at the restrictive condition fails to manufacture sufficient succinyl-coenzyme A. We explain the ammonia sensitivity by the dual role of alpha-ketoglutarate as substrate for the formation of succinyl-coenzyme A and glutamate. A defect in the enzyme necessary for the production of succinyl-coenzyme A makes ammonia an overly effective competitor for alpha-ketoglutarate."} {"id": "PMID:1262317", "title": "Ultrastructure of the cell walls of two closely related clostridia that possess different regular arrays of surface subunits.", "content": "Cell walls of Clostridium thermohydrosulfuricum and C. thermosaccharolyticum have a two-layered structure, consisting of a thin, lysozyme-sensitive murein layer and a surface (S) layer composed of hexagonally or tetragonally arranged subunits. The subunits can be removed from the murein layer by treatment of cell wall preparations, are composed of a fragile, pH-sensitive monolayer of macromolecular subunits. In both organisms the first stage of the cell division process involves only the plasma membrane and the murein layer. During the subsequent cell separation, a surplus of S-layer subunits appears at the site of division, and consequently the newly formed cell poles remain completely covered by the s layer throughout the separation process. In autolyzed cells an additional layer of subunits assembles on extended areas of the inside of the mucopeptide layer. These observations indicate that the biological function of the S layer depends on its ability to maintain a complete covering of the cell surface at all stages of cell growth and division.", "contents": "Ultrastructure of the cell walls of two closely related clostridia that possess different regular arrays of surface subunits. Cell walls of Clostridium thermohydrosulfuricum and C. thermosaccharolyticum have a two-layered structure, consisting of a thin, lysozyme-sensitive murein layer and a surface (S) layer composed of hexagonally or tetragonally arranged subunits. The subunits can be removed from the murein layer by treatment of cell wall preparations, are composed of a fragile, pH-sensitive monolayer of macromolecular subunits. In both organisms the first stage of the cell division process involves only the plasma membrane and the murein layer. During the subsequent cell separation, a surplus of S-layer subunits appears at the site of division, and consequently the newly formed cell poles remain completely covered by the s layer throughout the separation process. In autolyzed cells an additional layer of subunits assembles on extended areas of the inside of the mucopeptide layer. These observations indicate that the biological function of the S layer depends on its ability to maintain a complete covering of the cell surface at all stages of cell growth and division."} {"id": "PMID:1262318", "title": "Ultrastructure of developing ascospores in Sordaria brevicollis.", "content": "The ultrastructure of ascospore wall formation in the pyrenomycete Sordaria brevicollis was studied in developing asci at progressive time intervals. From early spore delimitation through final stage of maturation, the wall of the ascospore differentiated into four composite layers, the periascosporium the delineation ascosporium, the subascosproium, and the endoascosproium, While ascospores were at the hyaline stage of development,they possessed only the periascosporium and delineation ascosporium as their wall components. At about 7 to 8 days from the initiation of the cross, the spores developed a yellow color, and this coloration was always associated with the elaboration of the subascorsporium just internal to the ascosporium. Asthe spores continued to progressively darken in color, the subascosporium was seen to increase in complexity, electron density, and thickness. Soon after the formation of the subascosporium, the endoascosporium began to develop de novo and was, therefore, the last wall layer formed as the spore approached maturity.", "contents": "Ultrastructure of developing ascospores in Sordaria brevicollis. The ultrastructure of ascospore wall formation in the pyrenomycete Sordaria brevicollis was studied in developing asci at progressive time intervals. From early spore delimitation through final stage of maturation, the wall of the ascospore differentiated into four composite layers, the periascosporium the delineation ascosporium, the subascosproium, and the endoascosproium, While ascospores were at the hyaline stage of development,they possessed only the periascosporium and delineation ascosporium as their wall components. At about 7 to 8 days from the initiation of the cross, the spores developed a yellow color, and this coloration was always associated with the elaboration of the subascorsporium just internal to the ascosporium. Asthe spores continued to progressively darken in color, the subascosporium was seen to increase in complexity, electron density, and thickness. Soon after the formation of the subascosporium, the endoascosporium began to develop de novo and was, therefore, the last wall layer formed as the spore approached maturity."} {"id": "PMID:1262319", "title": "Cortex content of asporogenous mutants of Bacillus subtilis.", "content": "A method for the measurement of muramic lactam, which is specifically located in the cortical peptidoglycan of bacterial spores, was developed as a quantitative assay method for spore cortex content. During sporulation of Bacillus subtilis 168, muramic lactam (i.e., spore cortex) began to appear at state IV of sporulation and continued to increase over most of the late stages of sporulation. Spore cortex contents of various spo mutants of B. subitils were surveyed. Cortex was not detected in mutants in which sporulation was blocked earlier than stage II sporulation. Spores of spo IV mutant had about 40% of the cortex content of the wild-type spores. One spo III mutant had a low amount of cortex, but four others had none.", "contents": "Cortex content of asporogenous mutants of Bacillus subtilis. A method for the measurement of muramic lactam, which is specifically located in the cortical peptidoglycan of bacterial spores, was developed as a quantitative assay method for spore cortex content. During sporulation of Bacillus subtilis 168, muramic lactam (i.e., spore cortex) began to appear at state IV of sporulation and continued to increase over most of the late stages of sporulation. Spore cortex contents of various spo mutants of B. subitils were surveyed. Cortex was not detected in mutants in which sporulation was blocked earlier than stage II sporulation. Spores of spo IV mutant had about 40% of the cortex content of the wild-type spores. One spo III mutant had a low amount of cortex, but four others had none."} {"id": "PMID:1262320", "title": "Genetic mapping of leucine and isoleucine-valine loci in Rhizobium japonicum.", "content": "Leucine and isoleucine-valine loci have been mapped in Rhizobium japonicum. Transformation analysis suggests a common pathway for isoleucine-valine biosynthesis. Three-point reciprocal crosses indicated that all the leucine loci are not genetically linked.", "contents": "Genetic mapping of leucine and isoleucine-valine loci in Rhizobium japonicum. Leucine and isoleucine-valine loci have been mapped in Rhizobium japonicum. Transformation analysis suggests a common pathway for isoleucine-valine biosynthesis. Three-point reciprocal crosses indicated that all the leucine loci are not genetically linked."} {"id": "PMID:1262321", "title": "Demonstration and possible function of NADH:NAD+ transhydrogenase from ascaris muscle mitochondria.", "content": "Mitochondria from the muscle of Ascaris lumbricoides var. suis function anaerobically. NADH is generated in the intermembrane space as a consequence of the \"malic\" enzyme reaction. It has been suggested that this reducing equivalent in the form of hydride ion, would be translocated across the inner membrane in order to mediate ATP generation via the fumarate reductase reaction. In accord with this suggestion, intact Ascaris mitochondria showed appreciable NADH oxidase activity. Sonication resulted in an approximately 2-fold increase in NADH oxidase activity, whereas \"malic\" enzyme, fumarase, and NADH:NAD+ transhydrogenase activities increased approximately 7- to 14-fold, respectively. Phosphorylation capabilities and permeability toward pyridine nucleotides also indicated the intactness of the mitochondria. Ascaris mitochondria incubated anaerobically in the presence of fumarate, and [14C]NADH catalyzed a rapid reduction of the fumarate to succinate with the concomitant formation of equivalent quantities of extramitochondrial NAD+. However, very little isotope was recovered from the washed mitochondria, indicating the possibility of hydride ion translocation in the absence of nucleotide translocation. NADH:NAD+ transhydrogenase has been isolated from the muscle mitochondria of the intestinal nematode, Ascaris lumbricoides var. suis. The enzyme seems to have been solubilized from the mitochondrial membrane fraction by treatment with sodium deoxycholate followed by dialysis and subsequent adsorption by and elution from alumina C gamma. No NADPH:NAD+ transhydrogenase activity was detectable, making the Ascaris system unique over others reported. Activity was protected by L-cysteine, reduced glutathione and dithioerythritol, but strongly inhibited by low concentrations of p-chloromercuribenzoate or silver nitrate. The thionicotinamide derivative of NAD+ (thioNAD+) was employed to accept hydride ions from NADH in order to assay spectrophotometrically at 398 nm. Apparent Km values for thioNAD+ and NADH were 1 X 10(-4) M and 8 X 10(-6) M, respectively. That the physiological nucleotide, could act as hydride ion acceptor from NADH was indicated by the findings that NAD+ competitively inhibited the reduction of thioNAD+ when assayed at 398 nm. The additional finding of a noncompetitive inhibition between NAD+ and NADH suggested at least two binding sites on the enzyme, one for NADH and another common site for NAD+ and thioNAD+. More conclusive evidence indicating the participation of NAD+ as acceptor was obtained by incubation of the enzyme with NADH and [14C]NAD+ and demonstrating a rapid formation of [14C]NADH. These findings, in conjunction with those discussed above, suggest a physiological function of this enzyme in hydride ion translocation.", "contents": "Demonstration and possible function of NADH:NAD+ transhydrogenase from ascaris muscle mitochondria. Mitochondria from the muscle of Ascaris lumbricoides var. suis function anaerobically. NADH is generated in the intermembrane space as a consequence of the \"malic\" enzyme reaction. It has been suggested that this reducing equivalent in the form of hydride ion, would be translocated across the inner membrane in order to mediate ATP generation via the fumarate reductase reaction. In accord with this suggestion, intact Ascaris mitochondria showed appreciable NADH oxidase activity. Sonication resulted in an approximately 2-fold increase in NADH oxidase activity, whereas \"malic\" enzyme, fumarase, and NADH:NAD+ transhydrogenase activities increased approximately 7- to 14-fold, respectively. Phosphorylation capabilities and permeability toward pyridine nucleotides also indicated the intactness of the mitochondria. Ascaris mitochondria incubated anaerobically in the presence of fumarate, and [14C]NADH catalyzed a rapid reduction of the fumarate to succinate with the concomitant formation of equivalent quantities of extramitochondrial NAD+. However, very little isotope was recovered from the washed mitochondria, indicating the possibility of hydride ion translocation in the absence of nucleotide translocation. NADH:NAD+ transhydrogenase has been isolated from the muscle mitochondria of the intestinal nematode, Ascaris lumbricoides var. suis. The enzyme seems to have been solubilized from the mitochondrial membrane fraction by treatment with sodium deoxycholate followed by dialysis and subsequent adsorption by and elution from alumina C gamma. No NADPH:NAD+ transhydrogenase activity was detectable, making the Ascaris system unique over others reported. Activity was protected by L-cysteine, reduced glutathione and dithioerythritol, but strongly inhibited by low concentrations of p-chloromercuribenzoate or silver nitrate. The thionicotinamide derivative of NAD+ (thioNAD+) was employed to accept hydride ions from NADH in order to assay spectrophotometrically at 398 nm. Apparent Km values for thioNAD+ and NADH were 1 X 10(-4) M and 8 X 10(-6) M, respectively. That the physiological nucleotide, could act as hydride ion acceptor from NADH was indicated by the findings that NAD+ competitively inhibited the reduction of thioNAD+ when assayed at 398 nm. The additional finding of a noncompetitive inhibition between NAD+ and NADH suggested at least two binding sites on the enzyme, one for NADH and another common site for NAD+ and thioNAD+. More conclusive evidence indicating the participation of NAD+ as acceptor was obtained by incubation of the enzyme with NADH and [14C]NAD+ and demonstrating a rapid formation of [14C]NADH. These findings, in conjunction with those discussed above, suggest a physiological function of this enzyme in hydride ion translocation."} {"id": "PMID:1262322", "title": "Characterization of proteins from Ascaris lumbricoides which bind specifically to carboxypeptidase.", "content": "Inhibitors of the peptidase and esterase activities of carboxypeptidases A and B have been isolated from extracts of Ascaris lumbricoides var suis. These proteins were obtained by treatment of the aqueous extracts at low pH, precipitation with ammonium sulfate, molecular sieving on Bio-Gel P-4, and chromatography on DEAE-cellulose. The inhibitors were resolved into three homogeneous peaks on CM-cellulose. These components, CM-A, CM-B, and CM-C, have constant specific activity and were recovered in a 41% yield. They moved as single bands when subjected to electrophoresis at high or low pH on polyacrylamide gels and they have similar amino acid compositions. Methionine, tyrosine, and cysteine are absent from each of the inhibitors. The 65 residues of CM-B suggest a minimum molecular weight of 7530, in close agreement to the value of 7600 +/- 200 determined on a Bio-Gel P-100 column. Each of the proteins has the same NH2-terminal residues, NH2-Asx-Glx-Val-Glx- and the same COOH-terminal residue, leucine. A plot of per cent acrylamide versus log relative mobility suggests that the three proteins are charge isomers. CM-B appears to be stable to high NaCl concentrations, extremes of pH, high temperatures, and digestion by intestinal proteases. Carboxypeptidase C, carboxypeptidase N, and yeast protease C are not inhibited by CM-B. However, the exopeptidase and esterase activities of human carboxypeptidase A are inhibited. The inhibitors appear to bind to bovine carboxypeptidase A with an atypical stoichiometry. Two moles of CM-B inhibitor bind to 1 mol of enzyme. The evidence is: (a) a demonstrated purity of bovine carboxypeptidase A, (b) minimal and maximal inhibitor molecular weights by different methods, of 7600 and 8300, and (c) a maximum specific activity of apparently homogeneous inhibitors which is 50% of that predicted for unit stoichiometry.", "contents": "Characterization of proteins from Ascaris lumbricoides which bind specifically to carboxypeptidase. Inhibitors of the peptidase and esterase activities of carboxypeptidases A and B have been isolated from extracts of Ascaris lumbricoides var suis. These proteins were obtained by treatment of the aqueous extracts at low pH, precipitation with ammonium sulfate, molecular sieving on Bio-Gel P-4, and chromatography on DEAE-cellulose. The inhibitors were resolved into three homogeneous peaks on CM-cellulose. These components, CM-A, CM-B, and CM-C, have constant specific activity and were recovered in a 41% yield. They moved as single bands when subjected to electrophoresis at high or low pH on polyacrylamide gels and they have similar amino acid compositions. Methionine, tyrosine, and cysteine are absent from each of the inhibitors. The 65 residues of CM-B suggest a minimum molecular weight of 7530, in close agreement to the value of 7600 +/- 200 determined on a Bio-Gel P-100 column. Each of the proteins has the same NH2-terminal residues, NH2-Asx-Glx-Val-Glx- and the same COOH-terminal residue, leucine. A plot of per cent acrylamide versus log relative mobility suggests that the three proteins are charge isomers. CM-B appears to be stable to high NaCl concentrations, extremes of pH, high temperatures, and digestion by intestinal proteases. Carboxypeptidase C, carboxypeptidase N, and yeast protease C are not inhibited by CM-B. However, the exopeptidase and esterase activities of human carboxypeptidase A are inhibited. The inhibitors appear to bind to bovine carboxypeptidase A with an atypical stoichiometry. Two moles of CM-B inhibitor bind to 1 mol of enzyme. The evidence is: (a) a demonstrated purity of bovine carboxypeptidase A, (b) minimal and maximal inhibitor molecular weights by different methods, of 7600 and 8300, and (c) a maximum specific activity of apparently homogeneous inhibitors which is 50% of that predicted for unit stoichiometry."} {"id": "PMID:1262323", "title": "Pigeon liver amidophosphoribosyltransferase. Ligand-induced alterations in molecular and kinetic properties.", "content": "Amidophosphoribosyltransferase (EC 2.4.2.14) has been partially purified from pigeon liver, and ligand-induced alterations in molecular and kinetic properties have been studied. In Tris-HCl buffer the predominant form of the enzyme has an s20,w of 5.9 +/- 0.7, Stokes radium of 42 A, and estimated molecular weight of 102,000. Incubation with phosphoribosylpyrophosphate (PP-ribose-P) results in an increase in the s20,w to 7.9 +/- 0.6, Stokes radius to 53 A, and estimated molecular weight to 172,000. Incubation of this larger form with purine ribonucleotides leads to a decrease in the molecular weight of amidophosphoribosyltransferase that is proportional to the concentration of purine ribonucleotide. Purine ribonucleotides produce sigmoidal kinetics with respect to the substrate PP-ribose-P, with Hill coefficients of 1.4 to 1.6 and 1.8 to 2.0 in the presence of AMP and GMP, respectively. Incubation with 0.6 M KCl leads to sigmoidal kinetics. Hill coefficient of 1.8 and dissociation of the larger form of amidophosphoribosyltransferase. Inorganic phosphate has complex effects upon the enzyme. In 25 mM potassium phosphate buffer the enzyme aggregates to a large form with an s20,w of 8.3 +/- 0.2, Stokes radius of 53 A, and estimated molecular weight of 181,000. Inorganic phosphate and PP-ribose-P both stabilize the enzyme to storage in vitro at 4 degrees. However, inorganic phosphate is 4 times more effective than PP-ribose-P in preventing inactivation of the enzyme by sodium dodecyl sulfate. Inorganic phosphate produces sigmoidal kinetics with respect to PP-ribose-P, Hill coefficient of 1.5. The interaction coefficients for AMP and GMP are reduced from 1.8 to 1.2 and 2.2 to 1.4, respectively, in the presence of 25 mM potassium phosphate. It is concluded that pigeon liver amidophosphoribosyltransferase is a complex allosteric protein whose activity is regulated by a series of conformational changes induced by a number of ligands.", "contents": "Pigeon liver amidophosphoribosyltransferase. Ligand-induced alterations in molecular and kinetic properties. Amidophosphoribosyltransferase (EC 2.4.2.14) has been partially purified from pigeon liver, and ligand-induced alterations in molecular and kinetic properties have been studied. In Tris-HCl buffer the predominant form of the enzyme has an s20,w of 5.9 +/- 0.7, Stokes radium of 42 A, and estimated molecular weight of 102,000. Incubation with phosphoribosylpyrophosphate (PP-ribose-P) results in an increase in the s20,w to 7.9 +/- 0.6, Stokes radius to 53 A, and estimated molecular weight to 172,000. Incubation of this larger form with purine ribonucleotides leads to a decrease in the molecular weight of amidophosphoribosyltransferase that is proportional to the concentration of purine ribonucleotide. Purine ribonucleotides produce sigmoidal kinetics with respect to the substrate PP-ribose-P, with Hill coefficients of 1.4 to 1.6 and 1.8 to 2.0 in the presence of AMP and GMP, respectively. Incubation with 0.6 M KCl leads to sigmoidal kinetics. Hill coefficient of 1.8 and dissociation of the larger form of amidophosphoribosyltransferase. Inorganic phosphate has complex effects upon the enzyme. In 25 mM potassium phosphate buffer the enzyme aggregates to a large form with an s20,w of 8.3 +/- 0.2, Stokes radius of 53 A, and estimated molecular weight of 181,000. Inorganic phosphate and PP-ribose-P both stabilize the enzyme to storage in vitro at 4 degrees. However, inorganic phosphate is 4 times more effective than PP-ribose-P in preventing inactivation of the enzyme by sodium dodecyl sulfate. Inorganic phosphate produces sigmoidal kinetics with respect to PP-ribose-P, Hill coefficient of 1.5. The interaction coefficients for AMP and GMP are reduced from 1.8 to 1.2 and 2.2 to 1.4, respectively, in the presence of 25 mM potassium phosphate. It is concluded that pigeon liver amidophosphoribosyltransferase is a complex allosteric protein whose activity is regulated by a series of conformational changes induced by a number of ligands."} {"id": "PMID:1262324", "title": "Biohydrogenation of unsaturated fatty acids. Hydrogenation by cell-free preparations of Butyrivibrio fibrisolvens.", "content": "Hydrogenation of cis-9,trans-11-octadecadienoic acid to yield trans-11-octadecenoic acid by cell-free preparations of Butyrivibrio fibrisolvens has been obtained under strictly anaerobic conditions. Reduced methyl viologen, NADH, and an endogenous electron donor each can serve as a reductant. Inhibition studies and gel filtration patterns reveal the presence of at least two hydrogenation systems, one of which is coupled through a flavin, possibly FMN. Although the enzymes comprising the biohydrogenation pathway, the fatty acid reductases and linoleic acid isomerase, are part of the bacterial membrane, they do not appear to be constituted as a multienzyme complex.", "contents": "Biohydrogenation of unsaturated fatty acids. Hydrogenation by cell-free preparations of Butyrivibrio fibrisolvens. Hydrogenation of cis-9,trans-11-octadecadienoic acid to yield trans-11-octadecenoic acid by cell-free preparations of Butyrivibrio fibrisolvens has been obtained under strictly anaerobic conditions. Reduced methyl viologen, NADH, and an endogenous electron donor each can serve as a reductant. Inhibition studies and gel filtration patterns reveal the presence of at least two hydrogenation systems, one of which is coupled through a flavin, possibly FMN. Although the enzymes comprising the biohydrogenation pathway, the fatty acid reductases and linoleic acid isomerase, are part of the bacterial membrane, they do not appear to be constituted as a multienzyme complex."} {"id": "PMID:1262325", "title": "13C NMR spectroscopy of labeled pyridoxal 5'-phosphate. Model studies, D-serine dehydratase, and L-glutamate decarboxylase.", "content": "Pyridoxal 5'-phosphate labeled to the extent of 90% with 13C in the 4' (aldehyde) and 5' (methylene) positions has been synthesized. 13C NMR spectra of this material and of natural abundance pyridoxal 5'-phosphate are reported, as well as 13C NMR spectra of the Schiff base formed by reaction of pyridoxal 5'-phosphate with n-butylamine, the secondary amine formed by reduction of this Schiff base, the thiazolidine formed by reaction of pyridoxal 5'-phosphate with cysteine, the hexahydropyrimidine formed by reaction of pyridoxal 5'-phosphate with 1,3-diaminobutane, and pyridoxamine 5'-phosphate. The range of chemical shifts for carbon 4' in these compounds is more than 100 ppm, and thus this chemical shift is expected to be a sensitive indicator of structure in enzyme-bound pyridoxal 5'-phosphate. The chemical shift of carbon 5', on the other hand, is insensitive to these structure changes. 13C NMR spectra have been obtained at pH 7.8 and 9.4 for D-serine dehydratase (Mr = 46,000) containing natural abundance pyridoxal 5'-phosphate and containing 13C-enriched pyridoxal 5'-phosphate. The enriched material contains two new resonances not present in the natural abundance material, one at 167.7 ppm with a linewidth of approximately 24 Hz, attributed to carbon 4' of the Schiff base in the bound coenzyme, and one at 62.7 Hz with a linewidth of approximately 48 Hz attributed to carbon 5' of the bound Schiff base. A large number of resonances due to individual amino acids are assigned. The NMR spectrum changes only slightly when the pH is raised to 9.4. The widths of the two enriched coenzyme resonances indicate that the coenzyme is rather rigidly bound to the enzyme but probably has limited motional freedom relative to the protein. 13C NMR spectra have been obtained for L-glutamate decarboxylase containing natural abundance pyridoxal 5'-phosphate and 13C-enriched pyridoxal 5'-phosphate. Under conditions where the two enriched 13C resonances are clearly visible in D-serine dehydratase, no resonances are visible in enriched L-glutamate decarboxylase, presumably because the coenzyme is rigidly bound to the protein and the 300,000 molecular weight of this enzyme produces very short relaxation times for the bound coenzyme and thus very broad lines.", "contents": "13C NMR spectroscopy of labeled pyridoxal 5'-phosphate. Model studies, D-serine dehydratase, and L-glutamate decarboxylase. Pyridoxal 5'-phosphate labeled to the extent of 90% with 13C in the 4' (aldehyde) and 5' (methylene) positions has been synthesized. 13C NMR spectra of this material and of natural abundance pyridoxal 5'-phosphate are reported, as well as 13C NMR spectra of the Schiff base formed by reaction of pyridoxal 5'-phosphate with n-butylamine, the secondary amine formed by reduction of this Schiff base, the thiazolidine formed by reaction of pyridoxal 5'-phosphate with cysteine, the hexahydropyrimidine formed by reaction of pyridoxal 5'-phosphate with 1,3-diaminobutane, and pyridoxamine 5'-phosphate. The range of chemical shifts for carbon 4' in these compounds is more than 100 ppm, and thus this chemical shift is expected to be a sensitive indicator of structure in enzyme-bound pyridoxal 5'-phosphate. The chemical shift of carbon 5', on the other hand, is insensitive to these structure changes. 13C NMR spectra have been obtained at pH 7.8 and 9.4 for D-serine dehydratase (Mr = 46,000) containing natural abundance pyridoxal 5'-phosphate and containing 13C-enriched pyridoxal 5'-phosphate. The enriched material contains two new resonances not present in the natural abundance material, one at 167.7 ppm with a linewidth of approximately 24 Hz, attributed to carbon 4' of the Schiff base in the bound coenzyme, and one at 62.7 Hz with a linewidth of approximately 48 Hz attributed to carbon 5' of the bound Schiff base. A large number of resonances due to individual amino acids are assigned. The NMR spectrum changes only slightly when the pH is raised to 9.4. The widths of the two enriched coenzyme resonances indicate that the coenzyme is rather rigidly bound to the enzyme but probably has limited motional freedom relative to the protein. 13C NMR spectra have been obtained for L-glutamate decarboxylase containing natural abundance pyridoxal 5'-phosphate and 13C-enriched pyridoxal 5'-phosphate. Under conditions where the two enriched 13C resonances are clearly visible in D-serine dehydratase, no resonances are visible in enriched L-glutamate decarboxylase, presumably because the coenzyme is rigidly bound to the protein and the 300,000 molecular weight of this enzyme produces very short relaxation times for the bound coenzyme and thus very broad lines."} {"id": "PMID:1262326", "title": "Raman spectra of a solid antifreeze glycoprotein and its liquid and frozen aqueous solutions.", "content": "Raman spectroscopy was used to study the anomalous decrease in the freezing temperature of water produced by an antifreeze glycoprotein obtained from the sera of an Antarctic fish. An active fraction of this glycoprotein has a molecular weight of approximately 18,000 by equilibrium sedimentation compared to an apparent weight of 20 by freezing temperature depression. The Raman spectra of water present in a 1% antifreeze glycoprotein solution and of ice frozen from this solution were indistinguishable from the spectra of pure water and ice, respectively. These results indicate that the bulk properties of water and ice are unaffected by the presence of the antifreeze glycoprotein. Raman measurements on ice grown slowly, using as seed an oriented single crystal of ice in contact with 1% glycoprotein solutions, showed that the active glycoprotein was not excluded from the ice phase. On the other hand, we found that a smaller, inactive glycoprotein was excluded. Comparison of the Raman spectra of active and inactive glycoprotein components as solids, in 5% solutions, and rapidly frozen 5% solutions, showed that the two components differ in conformation and possibly in the environment of their carbohydrate hydroxyls. These observations suggest that hydrogen bonding of the carbohydrate hydroxyls of the active glycoprotein at the ice-solution interface may physically prevent growth of the ice lattice.", "contents": "Raman spectra of a solid antifreeze glycoprotein and its liquid and frozen aqueous solutions. Raman spectroscopy was used to study the anomalous decrease in the freezing temperature of water produced by an antifreeze glycoprotein obtained from the sera of an Antarctic fish. An active fraction of this glycoprotein has a molecular weight of approximately 18,000 by equilibrium sedimentation compared to an apparent weight of 20 by freezing temperature depression. The Raman spectra of water present in a 1% antifreeze glycoprotein solution and of ice frozen from this solution were indistinguishable from the spectra of pure water and ice, respectively. These results indicate that the bulk properties of water and ice are unaffected by the presence of the antifreeze glycoprotein. Raman measurements on ice grown slowly, using as seed an oriented single crystal of ice in contact with 1% glycoprotein solutions, showed that the active glycoprotein was not excluded from the ice phase. On the other hand, we found that a smaller, inactive glycoprotein was excluded. Comparison of the Raman spectra of active and inactive glycoprotein components as solids, in 5% solutions, and rapidly frozen 5% solutions, showed that the two components differ in conformation and possibly in the environment of their carbohydrate hydroxyls. These observations suggest that hydrogen bonding of the carbohydrate hydroxyls of the active glycoprotein at the ice-solution interface may physically prevent growth of the ice lattice."} {"id": "PMID:1262327", "title": "The effect of superhelicity on the interaction of histone f1 with closed circular duplex DNA.", "content": "A set of covalently closed circular duplex simian virus 40 DNA preparations of varying superhelical densities was prepared by closure of nicked duplex DNA with polynucleotide ligase in the presence of varying amounts of ethidium. The resulting molecules were tested for complex formation with the lysine-rich histone f1. The results confirmed earlier experiments in demonstrating that f1 histone reacts preferentially with superhelical DNA compared to relaxed circular DNA. Furthermore, the extent of the reaction is demonstrated to depend on the superhelical density. At the relatively low ratios of histone to DNA used in these experiments, the product of the interaction of f1 histone with superhelical DNA does not precipitate. At higher ratios of histone to DNA, an insoluble aggregate is formed.", "contents": "The effect of superhelicity on the interaction of histone f1 with closed circular duplex DNA. A set of covalently closed circular duplex simian virus 40 DNA preparations of varying superhelical densities was prepared by closure of nicked duplex DNA with polynucleotide ligase in the presence of varying amounts of ethidium. The resulting molecules were tested for complex formation with the lysine-rich histone f1. The results confirmed earlier experiments in demonstrating that f1 histone reacts preferentially with superhelical DNA compared to relaxed circular DNA. Furthermore, the extent of the reaction is demonstrated to depend on the superhelical density. At the relatively low ratios of histone to DNA used in these experiments, the product of the interaction of f1 histone with superhelical DNA does not precipitate. At higher ratios of histone to DNA, an insoluble aggregate is formed."} {"id": "PMID:1262328", "title": "alpha-L-Fucopyranosylceramide, a novel glycolipid accumulated in some of the human colon tumors.", "content": "A fucosylceramide was isolated from a ceramide monohexoside fraction of human colon carcinomas by acetylation followed by preparative thin layer chromatography on Silica Gel G developed with butylacetate. It contained only fucose as the carbohydrate component and the ceramide moiety was characterized as N-palmitoyloctadecasphingenine as a predominant component. The structure of the compound was determined as alpha-L-fucopyranosylceramide by methylation analysis, mass spectrometry of permethylated and reduced glycolipid, and by enzymatic hydrolysis with alpha-L-fucosidase. The chemical concentration of this compound in colon tumor tissue depends on degree of malignancy: highly malignant metastatic deposits from colon cancers were 3 to 70 ng/mg of residue protein, whereas that of localized colon tumor was 0 to 2 ng/mg of protein residue. The present observation offers additional support for the occurrence of metabolic abnormality of fucolipids as membrane phenotype of malignancy as was suggested in previous studies (Yang, H-J., and Hakomori, S. (1971) J. Biol. Chem. 246, 1192-1200; Steiner, S., Brennan, P.J., Melnick, J. L. (1973) Nature New Biol. 245, 19-21).", "contents": "alpha-L-Fucopyranosylceramide, a novel glycolipid accumulated in some of the human colon tumors. A fucosylceramide was isolated from a ceramide monohexoside fraction of human colon carcinomas by acetylation followed by preparative thin layer chromatography on Silica Gel G developed with butylacetate. It contained only fucose as the carbohydrate component and the ceramide moiety was characterized as N-palmitoyloctadecasphingenine as a predominant component. The structure of the compound was determined as alpha-L-fucopyranosylceramide by methylation analysis, mass spectrometry of permethylated and reduced glycolipid, and by enzymatic hydrolysis with alpha-L-fucosidase. The chemical concentration of this compound in colon tumor tissue depends on degree of malignancy: highly malignant metastatic deposits from colon cancers were 3 to 70 ng/mg of residue protein, whereas that of localized colon tumor was 0 to 2 ng/mg of protein residue. The present observation offers additional support for the occurrence of metabolic abnormality of fucolipids as membrane phenotype of malignancy as was suggested in previous studies (Yang, H-J., and Hakomori, S. (1971) J. Biol. Chem. 246, 1192-1200; Steiner, S., Brennan, P.J., Melnick, J. L. (1973) Nature New Biol. 245, 19-21)."} {"id": "PMID:1262329", "title": "Terminal deoxynucleotidyltransferase. Serological studies and radioimmunoassay.", "content": "Mouse antisera against calf terminal deoxynucleotidyltransferase (terminal transferase) have been prepared. The sera have been used to characterize terminal transferase both by studying inhibition of enzyme activity and by developing a competition radioimmunoassay using highly purified 125I-labeled terminal transferase. By either assay, anti-terminal transferase serum did not cross-react significantly with calf DNA polymerases alpha and beta, Escherichia coli DNA polymerase I, or the reverse transcriptase of Moloney mouse leukemia virus. The calf terminal transferase did, however, share cross-reactive but not identical determinants with human and murine terminal transferase. The radioimmunoassay could detect as little as 2 ng of terminal transferase/mg of soluble protein in a tissue extract. Thymocytes were found to contain 280 ng of terminal transferase/mg of cell protein or about 1 X 10(5) molecules/cell; bone marrow had about 1% of the level of enzyme found in thymus. Extracts of spleen, peripheral white blood cells, lymph nodes, liver, muscle, and kidney all lacked detectable antigenicity of terminal transferase. These data indicate that terminal transferase is a tissue-specific enzyme and is not related to other DNA polymerases.", "contents": "Terminal deoxynucleotidyltransferase. Serological studies and radioimmunoassay. Mouse antisera against calf terminal deoxynucleotidyltransferase (terminal transferase) have been prepared. The sera have been used to characterize terminal transferase both by studying inhibition of enzyme activity and by developing a competition radioimmunoassay using highly purified 125I-labeled terminal transferase. By either assay, anti-terminal transferase serum did not cross-react significantly with calf DNA polymerases alpha and beta, Escherichia coli DNA polymerase I, or the reverse transcriptase of Moloney mouse leukemia virus. The calf terminal transferase did, however, share cross-reactive but not identical determinants with human and murine terminal transferase. The radioimmunoassay could detect as little as 2 ng of terminal transferase/mg of soluble protein in a tissue extract. Thymocytes were found to contain 280 ng of terminal transferase/mg of cell protein or about 1 X 10(5) molecules/cell; bone marrow had about 1% of the level of enzyme found in thymus. Extracts of spleen, peripheral white blood cells, lymph nodes, liver, muscle, and kidney all lacked detectable antigenicity of terminal transferase. These data indicate that terminal transferase is a tissue-specific enzyme and is not related to other DNA polymerases."} {"id": "PMID:1262330", "title": "Purification and properties of proline reductase from Clostridium sticklandii.", "content": "Proline reductase of Clostridium sticklandii is a membrane-bound protein and is released by treatment with detergents. The enzyme has been purified to homogeneity and is estimated by gel filtration and sedimentation equilibrium centrifugation to have a molecular weight of 298,000 to 327,000. A minimum molecular weight of 30,000 to 31,000 was calculated on the basis of sodium dodecyl sulfate-acrylamide gel electrophoresis and amino acid composition. Amino acid analysis showed a preponderance of acidic amino acids. No tryptophan was detected in the protein either spectrophotometrically or by amino acid analysis. A total of 20 sulfhydryl groups measured by titration of the reduced protein with 5,5'-dithiobis(2-nitrobenzoic acid) is in agreement with 20 cystic acid residues determined in hydrolysates of performic acid-oxidized protein. No molybdenum, iron, or selenium was found in the pure protein. Although NADH is the physiological electron donor for the proline reductase complex, the purified 300,000 molecular weight reductase component is inactive in the presence of NADH in vitro. Dithiothreitol, in contrast, can serve as electron donor both for unpurified (putative proline reductase complex) and purified proline reductase in vitro.", "contents": "Purification and properties of proline reductase from Clostridium sticklandii. Proline reductase of Clostridium sticklandii is a membrane-bound protein and is released by treatment with detergents. The enzyme has been purified to homogeneity and is estimated by gel filtration and sedimentation equilibrium centrifugation to have a molecular weight of 298,000 to 327,000. A minimum molecular weight of 30,000 to 31,000 was calculated on the basis of sodium dodecyl sulfate-acrylamide gel electrophoresis and amino acid composition. Amino acid analysis showed a preponderance of acidic amino acids. No tryptophan was detected in the protein either spectrophotometrically or by amino acid analysis. A total of 20 sulfhydryl groups measured by titration of the reduced protein with 5,5'-dithiobis(2-nitrobenzoic acid) is in agreement with 20 cystic acid residues determined in hydrolysates of performic acid-oxidized protein. No molybdenum, iron, or selenium was found in the pure protein. Although NADH is the physiological electron donor for the proline reductase complex, the purified 300,000 molecular weight reductase component is inactive in the presence of NADH in vitro. Dithiothreitol, in contrast, can serve as electron donor both for unpurified (putative proline reductase complex) and purified proline reductase in vitro."} {"id": "PMID:1262331", "title": "Differentiation of lymphoid cells. A selective anti-mitogenic component of normal serum which inhibits the induction of immunoglobulin production.", "content": "Rabbit lymph node cell populations cultured in vitro in the presence of fetal calf serum are induced to produce immunoglobulin M-secreting cells. The induction of such immunoglobulin production, measured by the capacity of the cell population to secrete immunoglobulins, was inhibited when cells were cultured with sera from a variety of species despite the presence of fetal calf serum. The addition of such inhibitory serum 36 hours after initiation of the cell culture or thereafter was without effect on the extent of induction of immunoglobulin production. On the other hand, the presence of inhibitory serum in culture during only the first 24 hours yielded the same inhibition as when serum was present throughout the 72-hour culture period. Inhibitory sera also suppressed the incorporation of thymidine into DNA. The induction of immunoglobulin production and the incorporation of thymidine into DNA were essentially equally inhibited by the same range of serum concentrations. Unlike conventional inhibitors of DNA synthesis, the inhibitory sera exhibited selective specificity with regard to the kind of cells that could be affected. Thus, such sera inhibited the DNA synthesis of lymph node cells cultured in the presence of fetal calf serum but did not inhibit concanavalin A-stimulated DNA synthesis of such cultured cells and, similarly, serum did not inhibit DNA synthesis of thymus cells cultured in the presence of fetal calf serum. The sera of all species examined were inhibitory except for fetal sera. As judged from a quantitative assay, bovine and porcine serum contained the highest titer of inhibitor, whereas sera from human, rat, mouse, and rabbit were clustered in a group exhibiting less inhibitor. Ascites fluid and lymph node extracellular fluids contained less inhibitor than found in the serum of the same animal and lysates of washed lymph node cells were devoid of inhibitor. Although fetal bovine serum and newborn bovine serum did not contain the inhibitor, it was detectable within 24 hours of parturition. The inhibitor is of relatively large apparent molecular weight (about 300,000) and has been purified about 70-fold.", "contents": "Differentiation of lymphoid cells. A selective anti-mitogenic component of normal serum which inhibits the induction of immunoglobulin production. Rabbit lymph node cell populations cultured in vitro in the presence of fetal calf serum are induced to produce immunoglobulin M-secreting cells. The induction of such immunoglobulin production, measured by the capacity of the cell population to secrete immunoglobulins, was inhibited when cells were cultured with sera from a variety of species despite the presence of fetal calf serum. The addition of such inhibitory serum 36 hours after initiation of the cell culture or thereafter was without effect on the extent of induction of immunoglobulin production. On the other hand, the presence of inhibitory serum in culture during only the first 24 hours yielded the same inhibition as when serum was present throughout the 72-hour culture period. Inhibitory sera also suppressed the incorporation of thymidine into DNA. The induction of immunoglobulin production and the incorporation of thymidine into DNA were essentially equally inhibited by the same range of serum concentrations. Unlike conventional inhibitors of DNA synthesis, the inhibitory sera exhibited selective specificity with regard to the kind of cells that could be affected. Thus, such sera inhibited the DNA synthesis of lymph node cells cultured in the presence of fetal calf serum but did not inhibit concanavalin A-stimulated DNA synthesis of such cultured cells and, similarly, serum did not inhibit DNA synthesis of thymus cells cultured in the presence of fetal calf serum. The sera of all species examined were inhibitory except for fetal sera. As judged from a quantitative assay, bovine and porcine serum contained the highest titer of inhibitor, whereas sera from human, rat, mouse, and rabbit were clustered in a group exhibiting less inhibitor. Ascites fluid and lymph node extracellular fluids contained less inhibitor than found in the serum of the same animal and lysates of washed lymph node cells were devoid of inhibitor. Although fetal bovine serum and newborn bovine serum did not contain the inhibitor, it was detectable within 24 hours of parturition. The inhibitor is of relatively large apparent molecular weight (about 300,000) and has been purified about 70-fold."} {"id": "PMID:1262332", "title": "Different mechanisms of energy coupling for transport of various amino acids in cells of Mycobacterium phlei.", "content": "Whole cells of Mycobacterium phlei were shown to actively accumulate proline, leucine, lysine, tryptophan, histidine, glutamine, and glutamic acid to different steady state levels. The transport of proline, in contrast to that of other amino acids, was found to be insensitive to various respiratory inhibitors, e.g. cyanide, arsenate, azide, and sulfhydryl reagents. However, oxygen was an obligatory requirement for the uptake of proline, as well as for the other amino acids. The results indicate that the energy requirements for proline uptake are different from those of other amino acids. In contrast to the system from Escherichia coli, the mode of energy transduction for the uptake of proline, glutamine, and glutamic acid is different even though these amino acids are shock resistant in the M. phlei system.", "contents": "Different mechanisms of energy coupling for transport of various amino acids in cells of Mycobacterium phlei. Whole cells of Mycobacterium phlei were shown to actively accumulate proline, leucine, lysine, tryptophan, histidine, glutamine, and glutamic acid to different steady state levels. The transport of proline, in contrast to that of other amino acids, was found to be insensitive to various respiratory inhibitors, e.g. cyanide, arsenate, azide, and sulfhydryl reagents. However, oxygen was an obligatory requirement for the uptake of proline, as well as for the other amino acids. The results indicate that the energy requirements for proline uptake are different from those of other amino acids. In contrast to the system from Escherichia coli, the mode of energy transduction for the uptake of proline, glutamine, and glutamic acid is different even though these amino acids are shock resistant in the M. phlei system."} {"id": "PMID:1262333", "title": "Mechanism of the thrombin-mediated burst in oxygen consumption by human platelets.", "content": "We present evidence that added thrombin stimulates release of endogenous arachidonic acid by suspensions of human platelets. We also show that added arachidonic acid causes a burst in O2 consumption that mimics one of the well described effects of thrombin on these cells. Further, added aspirin, a known inhibitor of the burst in O2 consumption caused by thrombin, also blunted the stimulatory effect of arachidonate on O2 consumption, and eicosatetraynoate, a known inhibitor of arachidonate oxygenation, blunted the burst in O2 consumption initiated by both thrombin and arachidonate. We conclude that rapid oxygenation of endogenously released arachidonic acid accounts for the thrombin-mediated burst in oxygen consumption by platelets.", "contents": "Mechanism of the thrombin-mediated burst in oxygen consumption by human platelets. We present evidence that added thrombin stimulates release of endogenous arachidonic acid by suspensions of human platelets. We also show that added arachidonic acid causes a burst in O2 consumption that mimics one of the well described effects of thrombin on these cells. Further, added aspirin, a known inhibitor of the burst in O2 consumption caused by thrombin, also blunted the stimulatory effect of arachidonate on O2 consumption, and eicosatetraynoate, a known inhibitor of arachidonate oxygenation, blunted the burst in O2 consumption initiated by both thrombin and arachidonate. We conclude that rapid oxygenation of endogenously released arachidonic acid accounts for the thrombin-mediated burst in oxygen consumption by platelets."} {"id": "PMID:1262334", "title": "Induced polypeptide synthesis during the development of bacterial bioluminescence.", "content": "The dramatic increase in bioluminescence observed during the later exponential growth of Beneckea harveyi is due to the induction of luciferase activity. The mechanism by which luciferase activity is induced and the possible existence of other induced proteins was investigated in a double-labelind experiment: [4,5-3H]leucine was incorporated into cellular proteins synthesized during the luminescence lag period in early growth; [14C]leucine was incorporated during the later period of luminescence induction. The protein of the cell-free extract were extensively fractionated and luciferase was purified to homogeneity. Analysis of the radioactivity incorporated into the alpha and beta subunits of luciferase showed a dramatic but equal decrease in the 3H/14C ratio for both subunits. This result proves that the synthesis of the alpha and beta chains of luciferase is subject to similar controls and that the regulatory mechanism is operative at the level of gene transcription, or translation at the time of bioluminescence induction, or both. Several additional polypeptides have been found which also show a marked decrease in their 3H/14C ratio indicating that their synthesis is induced during the same period as luciferase. In addition, one polypeptide that is synthesized specifically in the bioluminescence lag period was also detected. The function and role of these new polypeptides with respect to the bioluminescent system is presently under investigation.", "contents": "Induced polypeptide synthesis during the development of bacterial bioluminescence. The dramatic increase in bioluminescence observed during the later exponential growth of Beneckea harveyi is due to the induction of luciferase activity. The mechanism by which luciferase activity is induced and the possible existence of other induced proteins was investigated in a double-labelind experiment: [4,5-3H]leucine was incorporated into cellular proteins synthesized during the luminescence lag period in early growth; [14C]leucine was incorporated during the later period of luminescence induction. The protein of the cell-free extract were extensively fractionated and luciferase was purified to homogeneity. Analysis of the radioactivity incorporated into the alpha and beta subunits of luciferase showed a dramatic but equal decrease in the 3H/14C ratio for both subunits. This result proves that the synthesis of the alpha and beta chains of luciferase is subject to similar controls and that the regulatory mechanism is operative at the level of gene transcription, or translation at the time of bioluminescence induction, or both. Several additional polypeptides have been found which also show a marked decrease in their 3H/14C ratio indicating that their synthesis is induced during the same period as luciferase. In addition, one polypeptide that is synthesized specifically in the bioluminescence lag period was also detected. The function and role of these new polypeptides with respect to the bioluminescent system is presently under investigation."} {"id": "PMID:1262335", "title": "Immunochemical studies of serine dehydratase and ornithine aminotransferase regulation in rat liver in vivo.", "content": "Previous studies of serine dehydratase (EC 4.2.1.13) and ornithine aminotransferase (EC 2.6.1.13) adaptation in rat liver showed that in rats on a high protein diet, glucocorticoid administration increased serine dehydratase activity while simultaneously reducing the activity of ornithine aminotransferase. The present study examines the role of enzyme synthesis in the expression of these and other dissimilar adaptive characteristics of the two enzymes. Both enzymes were purified to crystallinity and used to prepare specific antibodies. Changes in the rate of synthesis of each enzyme during adaptation were then measured immunochemically. In rats fed ad libitum, the synthetic rates for both enzymes exhibited circadian rhythm, although enzyme levels remained relatively constant. The circadian cycle for ornithine aminotransferase synthesis was in phase with the cycles for body weight and relative liver weight (maxima at 9 a.m., minima at 9 p.m.) but was approximately 12 hours out of phase with the cycle for serine dehydratase synthesis. 9alpha-Fluoro-11beta, 21-dihydroxy-16alpha, 17alpha-isopted at 9 a.m., increased serine dehydratase synthesis and simultaneously decreased the synthesis of ornithine aminotransferase. When triamcinolone was injected at 9 p.m., however, serine dehydratase synthesis was not stimulated, although the reduction of ornithine aminotransferase synthesis was still produced. These results suggest that: (a) circadian cycling of synthesis may be a general phenomenon in enzyme regulation even though for enzymes with relatively long half-lives, such cycling may not be reflected as fluctuations in enzyme levels; (b) such circadian rhythmicity may also involve cyclic changes in the responsiveness of the enzyme-forming system to regulatory stimuli; (c) whereas the adaptive behavior of serine dehydratase typifies that of amino acid-catabolizing enzymes in general, the responses of ornithine aminotransferase denote a functional association of this enzyme with anabolic processes. On this basis, the possibility that ornithine aminotransferase plays a pivotal role in the regulation of urea cycle activity and nitrogen balance is discussed.", "contents": "Immunochemical studies of serine dehydratase and ornithine aminotransferase regulation in rat liver in vivo. Previous studies of serine dehydratase (EC 4.2.1.13) and ornithine aminotransferase (EC 2.6.1.13) adaptation in rat liver showed that in rats on a high protein diet, glucocorticoid administration increased serine dehydratase activity while simultaneously reducing the activity of ornithine aminotransferase. The present study examines the role of enzyme synthesis in the expression of these and other dissimilar adaptive characteristics of the two enzymes. Both enzymes were purified to crystallinity and used to prepare specific antibodies. Changes in the rate of synthesis of each enzyme during adaptation were then measured immunochemically. In rats fed ad libitum, the synthetic rates for both enzymes exhibited circadian rhythm, although enzyme levels remained relatively constant. The circadian cycle for ornithine aminotransferase synthesis was in phase with the cycles for body weight and relative liver weight (maxima at 9 a.m., minima at 9 p.m.) but was approximately 12 hours out of phase with the cycle for serine dehydratase synthesis. 9alpha-Fluoro-11beta, 21-dihydroxy-16alpha, 17alpha-isopted at 9 a.m., increased serine dehydratase synthesis and simultaneously decreased the synthesis of ornithine aminotransferase. When triamcinolone was injected at 9 p.m., however, serine dehydratase synthesis was not stimulated, although the reduction of ornithine aminotransferase synthesis was still produced. These results suggest that: (a) circadian cycling of synthesis may be a general phenomenon in enzyme regulation even though for enzymes with relatively long half-lives, such cycling may not be reflected as fluctuations in enzyme levels; (b) such circadian rhythmicity may also involve cyclic changes in the responsiveness of the enzyme-forming system to regulatory stimuli; (c) whereas the adaptive behavior of serine dehydratase typifies that of amino acid-catabolizing enzymes in general, the responses of ornithine aminotransferase denote a functional association of this enzyme with anabolic processes. On this basis, the possibility that ornithine aminotransferase plays a pivotal role in the regulation of urea cycle activity and nitrogen balance is discussed."} {"id": "PMID:1262336", "title": "Appearance of rapidly labeled, high molecular weight RNA in nuclear ribonucleoprotein. Release from chromatin and association with protein.", "content": "Chromatin and nuclear ribonucleoprotein (nRNP) have been prepared from a human carcinoma cell line. Following a 1-hour (3H)uridine pulse, 60 to 70% of the nuclear radioactivity, after removal of nucleoli, was found in the chromatin, the balance in nRNP. This was true whether the chromatin and nRNP were separated by velocity centrifugation or by isopycnic centrifugation on Metrizamide gradients. Radioactivity in chromatin and nRNP was found in high molecular weight RNA, with mean sedimentation coefficients of 20 S and 15 S, respectively, as determined on sodium dodecyl sulfate-sucrose gradients. Experiments on the kinetics of appearance of radioactivity in the RNA of the two fractions suggest that some of the chromatin-associated RNA is precursor to nRNP-RNA. The proteins of nRNP are complex as revealed by sodium dodecyl sulfate gel electrophoresis. The contamination by chromatin protein was estimated to be 5%. Experiments involving short pulses of (3H)tryptophan, and pulse-chase, suggested that the rapidly turning over proteins of nRNP were not complexed with RNA while still associated with chromatin. However, it was also shown that the radioactivity in nRNP following short pulses of (3H)tryptophan did not correspond to the major bands seen on stained sodium dodecyl sulfate gels. It is therefore concluded that the protein of nRNP consists of two classes: species present in large amounts, possibly common to all RNA in nRNP, which are relatively stable and may be complexed to RNA still associated with chromatin; and a large number of rapidly turning over species, each present in small amounts and associated with nRNP only after its release from chromatin.", "contents": "Appearance of rapidly labeled, high molecular weight RNA in nuclear ribonucleoprotein. Release from chromatin and association with protein. Chromatin and nuclear ribonucleoprotein (nRNP) have been prepared from a human carcinoma cell line. Following a 1-hour (3H)uridine pulse, 60 to 70% of the nuclear radioactivity, after removal of nucleoli, was found in the chromatin, the balance in nRNP. This was true whether the chromatin and nRNP were separated by velocity centrifugation or by isopycnic centrifugation on Metrizamide gradients. Radioactivity in chromatin and nRNP was found in high molecular weight RNA, with mean sedimentation coefficients of 20 S and 15 S, respectively, as determined on sodium dodecyl sulfate-sucrose gradients. Experiments on the kinetics of appearance of radioactivity in the RNA of the two fractions suggest that some of the chromatin-associated RNA is precursor to nRNP-RNA. The proteins of nRNP are complex as revealed by sodium dodecyl sulfate gel electrophoresis. The contamination by chromatin protein was estimated to be 5%. Experiments involving short pulses of (3H)tryptophan, and pulse-chase, suggested that the rapidly turning over proteins of nRNP were not complexed with RNA while still associated with chromatin. However, it was also shown that the radioactivity in nRNP following short pulses of (3H)tryptophan did not correspond to the major bands seen on stained sodium dodecyl sulfate gels. It is therefore concluded that the protein of nRNP consists of two classes: species present in large amounts, possibly common to all RNA in nRNP, which are relatively stable and may be complexed to RNA still associated with chromatin; and a large number of rapidly turning over species, each present in small amounts and associated with nRNP only after its release from chromatin."} {"id": "PMID:1262337", "title": "Characterization of KB cell alkaline phosphatase. Evidence of similarity to placental alkaline phosphatase.", "content": "The alkaline phosphatase from KB cells was purified, characterized, and compared to placental alkaline phosphatase, which it resembles immunologically. Two nonidentical nonomeric subunits of the KB phosphatase were found. The two subunits, which have apparent molecular weights of 64,000 and 72,000, can be separated on polyacrylamide gels containing sodium dodecyl sulfate. The Mr = 64,000 KB subunit appears to be identical in protein structure to the monomer of placental alkaline phosphatase. The Mr = 72,000 KB subunit, while differing in the NH2-terminal amino acid, appears also to be very similar to the placental alkaline phosphatase monomer. Both KB phosphatase subunits bind (32P)phosphate, and bind to Sepharose-bound anti-placental alkaline phosphatase. Native KB phosphatase is identical to the placental isozyme in isoelectric point, pH optimum, and inhibition by amino acids, and has a very similar peptide map. The data presented support the hypothesis that the Mr = 64,000 KB phosphatase subunit may the the same gene product as the monomer of placental alkaline phosphatase. This paper strengthens the evidence that the gene for this fetal protein, normally repressed in all cells but placenta, is derepressed in the KB cell line. In addition, this paper presents the first structural evidence that there are two different subunit proteins comprising the placental-like alkaline phosphatase from a human tumor cell line.", "contents": "Characterization of KB cell alkaline phosphatase. Evidence of similarity to placental alkaline phosphatase. The alkaline phosphatase from KB cells was purified, characterized, and compared to placental alkaline phosphatase, which it resembles immunologically. Two nonidentical nonomeric subunits of the KB phosphatase were found. The two subunits, which have apparent molecular weights of 64,000 and 72,000, can be separated on polyacrylamide gels containing sodium dodecyl sulfate. The Mr = 64,000 KB subunit appears to be identical in protein structure to the monomer of placental alkaline phosphatase. The Mr = 72,000 KB subunit, while differing in the NH2-terminal amino acid, appears also to be very similar to the placental alkaline phosphatase monomer. Both KB phosphatase subunits bind (32P)phosphate, and bind to Sepharose-bound anti-placental alkaline phosphatase. Native KB phosphatase is identical to the placental isozyme in isoelectric point, pH optimum, and inhibition by amino acids, and has a very similar peptide map. The data presented support the hypothesis that the Mr = 64,000 KB phosphatase subunit may the the same gene product as the monomer of placental alkaline phosphatase. This paper strengthens the evidence that the gene for this fetal protein, normally repressed in all cells but placenta, is derepressed in the KB cell line. In addition, this paper presents the first structural evidence that there are two different subunit proteins comprising the placental-like alkaline phosphatase from a human tumor cell line."} {"id": "PMID:1262338", "title": "Chloral hydrate causes breakdown of polysomes in Chlamydomonas reinhardi in vivo.", "content": "Chloral hydrate produces a biphasic change in the proportion in the cell. Within 1 to 2 min after addition to cells, it inhibits protein synthesis and causes polysomes to break down. The ribosomes dissociate from mRNA by a process which requires protein synthesis but which is apparently abnormal. Released ribosomes do not appear to be bound to fragments of mRNA, but do carry a nascent polypeptide chain. Protein synthesis remains inhibited by more than 85% for over 24 hours, but the apparently normal polyteraction of the cells with chloral hydrate itself and not from its conversion of its usual metabolic products, trichloroethanol or trichloroacetic acid.", "contents": "Chloral hydrate causes breakdown of polysomes in Chlamydomonas reinhardi in vivo. Chloral hydrate produces a biphasic change in the proportion in the cell. Within 1 to 2 min after addition to cells, it inhibits protein synthesis and causes polysomes to break down. The ribosomes dissociate from mRNA by a process which requires protein synthesis but which is apparently abnormal. Released ribosomes do not appear to be bound to fragments of mRNA, but do carry a nascent polypeptide chain. Protein synthesis remains inhibited by more than 85% for over 24 hours, but the apparently normal polyteraction of the cells with chloral hydrate itself and not from its conversion of its usual metabolic products, trichloroethanol or trichloroacetic acid."} {"id": "PMID:1262339", "title": "Metabolism of bile alcohols in the perfused rabbit liver.", "content": "The mechanism and sequence of side chain hydroxylation of cholesterol in bile acid synthesis was studied in the isolated perfused rabbit liver. A comparison was made between the importance of 26- and 25-hydroxylation in cholic acid biosynthesis in the rabbit. The formation of [G-3H]cholic acid was observed when the liver was perfused with 5beta-[G-3H]cholestane-3alpha, 7alpha-diol, 5beta-[G-3H]cholestane-3alpha, 7alpha-12alpha-triol, and 5beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol. No [G-3H]chenodeoxycholic acid was detected in the bile. These findings indicate that potential precursors of chenodeoxycholic acid were hydroxylated at position 12alpha either subsequent to or before hydroxylation of the cholesterol side chain. In addition, no other intermediates (tetrahydroxy or pentahydroxy bile alcohols) were found in the bile when these compounds were perfused in the liver. Bile acid precursors were detected in bile when the rabbit liver was perfused with 5beta-[24-14C]cholestane-3alpha, 7alpha, 25-triol. The 5beta-[24-14C]cholestane-3alpha, 7alpha, 25-triol was hydroxylated in the liver at the 12alpha position to yield the corresponding 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol. The tetrol was further metabolized to a series of pentols (5beta-cholestane-3alpha, 7alpha, 12alpha, 22, 25-pentol; 5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentol; 5beta-cholestane-3alpha, 7alpha, 12alpha, 24, 25-pentol; and 5beta-cholestane-3alpha, 7alpha, 12alpha, 25, 26-pentol). The major bile acid obtained from the perfusion of the 5beta-cholestane-3alpha, 7alpha, 25-triol was cholic acid. The experiments indicated that in the rabbit liver 12alpha-hydroxylation can occur after hydroxylation of the cholesterol side chain at either C-25 (5 beta-cholestane-3alpha, 7alpha, 25-triol) or C-26 (5beta-cholestane-3alpha, 7alpha-26-triol). Apparently, the rabbit can form cholic acid via the classical 26-hydroxylation pathway as well as via 25-hydroxylated intermediates.", "contents": "Metabolism of bile alcohols in the perfused rabbit liver. The mechanism and sequence of side chain hydroxylation of cholesterol in bile acid synthesis was studied in the isolated perfused rabbit liver. A comparison was made between the importance of 26- and 25-hydroxylation in cholic acid biosynthesis in the rabbit. The formation of [G-3H]cholic acid was observed when the liver was perfused with 5beta-[G-3H]cholestane-3alpha, 7alpha-diol, 5beta-[G-3H]cholestane-3alpha, 7alpha-12alpha-triol, and 5beta-[G-3H]cholestane-3alpha, 7alpha, 26-triol. No [G-3H]chenodeoxycholic acid was detected in the bile. These findings indicate that potential precursors of chenodeoxycholic acid were hydroxylated at position 12alpha either subsequent to or before hydroxylation of the cholesterol side chain. In addition, no other intermediates (tetrahydroxy or pentahydroxy bile alcohols) were found in the bile when these compounds were perfused in the liver. Bile acid precursors were detected in bile when the rabbit liver was perfused with 5beta-[24-14C]cholestane-3alpha, 7alpha, 25-triol. The 5beta-[24-14C]cholestane-3alpha, 7alpha, 25-triol was hydroxylated in the liver at the 12alpha position to yield the corresponding 5beta-cholestane-3alpha, 7alpha, 12alpha, 25-tetrol. The tetrol was further metabolized to a series of pentols (5beta-cholestane-3alpha, 7alpha, 12alpha, 22, 25-pentol; 5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentol; 5beta-cholestane-3alpha, 7alpha, 12alpha, 24, 25-pentol; and 5beta-cholestane-3alpha, 7alpha, 12alpha, 25, 26-pentol). The major bile acid obtained from the perfusion of the 5beta-cholestane-3alpha, 7alpha, 25-triol was cholic acid. The experiments indicated that in the rabbit liver 12alpha-hydroxylation can occur after hydroxylation of the cholesterol side chain at either C-25 (5 beta-cholestane-3alpha, 7alpha, 25-triol) or C-26 (5beta-cholestane-3alpha, 7alpha-26-triol). Apparently, the rabbit can form cholic acid via the classical 26-hydroxylation pathway as well as via 25-hydroxylated intermediates."} {"id": "PMID:1262341", "title": "Alpha-Amanitin resistance of RNA polymerase II in mutant Chinese hamster ovary cell lines.", "content": "A number of mutant Chinese hamster ovary (CHO) cell lines resistant to the cytotoxic action of alpha-amanitin have been isolated. The alpha-amanitin sensitivity of the different mutant cell lines varied widely, but correlated well with the alpha-amanitin sensitivity of the RNA polymerase II activity in each of these mutant cell lines. In comparison with the RNA polymerase II of wild-type cells, three mutants, Ama39, Ama6, and Amal, required respectively 2- to 3-fold, 8- to 10-fold, and about 800-fold higher concentrations of alpha-amanitin for inhibition of their polymerase II activity. Determination of the equilibrium dissociation constants (KD) for complexes between 0-[3H]methyl-demethyl-gamma-amanitin and RNA polymearse II indicated that differences in alpha-amanitin sensitivity were reflected in differences in the ability of the enzymes to bind amanitin. Hybrids formed by fusion of mutants with cells of wild-type sensitivity contained both mutant and wild-type polymerase II activities. Thus, each of the different alpha-amanitin resistance mutations was expressed co-dominantly. A test for complementation between two of these mutations by measurement of both the alpha-amanitin sensitivity and the [3H]amanitin binding by RNA polymerase II in Ama6 X Amal hybrid cells did not reveal any wild-type RNA polymerase II activity. These data provide evidence that the mutation to alpha-amanitin resistance involves structural changes in the gene coding for the alpha-amanitin binding subunit of RNA polymerase II. These changes appear to account for the alpha-amanitin-resistant phenotypes of these mutant cells.", "contents": "Alpha-Amanitin resistance of RNA polymerase II in mutant Chinese hamster ovary cell lines. A number of mutant Chinese hamster ovary (CHO) cell lines resistant to the cytotoxic action of alpha-amanitin have been isolated. The alpha-amanitin sensitivity of the different mutant cell lines varied widely, but correlated well with the alpha-amanitin sensitivity of the RNA polymerase II activity in each of these mutant cell lines. In comparison with the RNA polymerase II of wild-type cells, three mutants, Ama39, Ama6, and Amal, required respectively 2- to 3-fold, 8- to 10-fold, and about 800-fold higher concentrations of alpha-amanitin for inhibition of their polymerase II activity. Determination of the equilibrium dissociation constants (KD) for complexes between 0-[3H]methyl-demethyl-gamma-amanitin and RNA polymearse II indicated that differences in alpha-amanitin sensitivity were reflected in differences in the ability of the enzymes to bind amanitin. Hybrids formed by fusion of mutants with cells of wild-type sensitivity contained both mutant and wild-type polymerase II activities. Thus, each of the different alpha-amanitin resistance mutations was expressed co-dominantly. A test for complementation between two of these mutations by measurement of both the alpha-amanitin sensitivity and the [3H]amanitin binding by RNA polymerase II in Ama6 X Amal hybrid cells did not reveal any wild-type RNA polymerase II activity. These data provide evidence that the mutation to alpha-amanitin resistance involves structural changes in the gene coding for the alpha-amanitin binding subunit of RNA polymerase II. These changes appear to account for the alpha-amanitin-resistant phenotypes of these mutant cells."} {"id": "PMID:1262340", "title": "The in vitro metabolism of mevalonate by sterol and non-sterol pathways.", "content": "The metabolism of mevalonic acid by both sterol and non-sterol pathways has been evaluated in nine tissues of the rat. An in vitro estimation of the non-sterol, or \"shunt\", pathway of mevalonate metabolism was made possible by determining the conversion of [2-14C]mevalonate or [5-14C]mevalonate to 14CO2 in tissue slices. In confirmation of our previous results, the kidney was found to play a major role in the metabolism of mevalonate to sterols and sterol precursors. The shunt pathway accounted for a significant percentage of the mevalonate metabolized in kidney, ileum, spleen, lung and testes, but was of minor importance or undetectable in liver, brain, skin, and adipose tissue. Kidney, however, proved to be by far the most active tissue site of mevalonate metabolism by the shunt mechanism in that, on an average, renal tissue metabolized (R)-[14C]mevalonate over the non-sterol pathway at a rate that was 21 times that of any other tissue examined. These results indicate that the kidneys are of major importance in the metabolism of mevalonate by each of the known pathways of metabolism of this sterol precursor.", "contents": "The in vitro metabolism of mevalonate by sterol and non-sterol pathways. The metabolism of mevalonic acid by both sterol and non-sterol pathways has been evaluated in nine tissues of the rat. An in vitro estimation of the non-sterol, or \"shunt\", pathway of mevalonate metabolism was made possible by determining the conversion of [2-14C]mevalonate or [5-14C]mevalonate to 14CO2 in tissue slices. In confirmation of our previous results, the kidney was found to play a major role in the metabolism of mevalonate to sterols and sterol precursors. The shunt pathway accounted for a significant percentage of the mevalonate metabolized in kidney, ileum, spleen, lung and testes, but was of minor importance or undetectable in liver, brain, skin, and adipose tissue. Kidney, however, proved to be by far the most active tissue site of mevalonate metabolism by the shunt mechanism in that, on an average, renal tissue metabolized (R)-[14C]mevalonate over the non-sterol pathway at a rate that was 21 times that of any other tissue examined. These results indicate that the kidneys are of major importance in the metabolism of mevalonate by each of the known pathways of metabolism of this sterol precursor."} {"id": "PMID:1262342", "title": "Function and structure in ribonucleic acid phage Qbeta ribonucleic acid replicase. Effect of inhibitors of EF-Tu on ribonucleic acid synthesis and renaturation of active enzyme.", "content": "Escherichia coli Phage Qbeta RNA replicase, an RNA-dependent RNA polymerase, is a tetramer composed of one phage-coded polypeptide and three host-supplied polypeptides which are known to function in the biosynthesis of proteins in the uninfected host. Two of these polypeptides, protein synthesis elongation factors EF-Tu and EF-Ts, are required for initiation of transcription by Qbeta replicase with all templates. Using a previously developed reconstitution system we have examined the effects of modification of EF-Tu on reconstituted replicase activity. The poly(G) polymerase activity of the enzyme can be recovered after pretreatment of the EF-Tu-GDP with either L-1-tosylamido-2-phenylethyl chloromethyl ketone or N-ethylmaleimide, both of which inhibit the aminoacyl-tRNA binding activity of EF-Tu. This suggests that the aminoacyl-tRNA binding site of EF-Tu is not required for Qbeta replicase activity. When Qbeta replicase is treated with kirromycin, an antibiotic which modifies EF-Tu activity by an unknown mechamism, the protein synthetic activity of the EF-Tu in the replicase complex is eliminated but the Qbeta RNA replication activity is only slightly affected. Treatment of pure EF-Tu with kirromycin, however, prevents it from functioning in the renaturation of Qbeta replicase. This antibiotic is not effective against the EF-Tu-Ts complex in the reconstitution assay. Kirromycin at the relatively high concentration used here is found to prevent the formation of the EF-Tu-Ts complex. GDP, which binds to EF-Tu and inhibits formation of the complex with EF-Ts, also inhibits renaturation of Qbeta replicase. It is suggested that the EF-Tu-Ts complex, rather than the individual polypeptides, functions in the renaturation of Qbeta replicase and that the kirromycin and GDP act by preventing formation of this complex.", "contents": "Function and structure in ribonucleic acid phage Qbeta ribonucleic acid replicase. Effect of inhibitors of EF-Tu on ribonucleic acid synthesis and renaturation of active enzyme. Escherichia coli Phage Qbeta RNA replicase, an RNA-dependent RNA polymerase, is a tetramer composed of one phage-coded polypeptide and three host-supplied polypeptides which are known to function in the biosynthesis of proteins in the uninfected host. Two of these polypeptides, protein synthesis elongation factors EF-Tu and EF-Ts, are required for initiation of transcription by Qbeta replicase with all templates. Using a previously developed reconstitution system we have examined the effects of modification of EF-Tu on reconstituted replicase activity. The poly(G) polymerase activity of the enzyme can be recovered after pretreatment of the EF-Tu-GDP with either L-1-tosylamido-2-phenylethyl chloromethyl ketone or N-ethylmaleimide, both of which inhibit the aminoacyl-tRNA binding activity of EF-Tu. This suggests that the aminoacyl-tRNA binding site of EF-Tu is not required for Qbeta replicase activity. When Qbeta replicase is treated with kirromycin, an antibiotic which modifies EF-Tu activity by an unknown mechamism, the protein synthetic activity of the EF-Tu in the replicase complex is eliminated but the Qbeta RNA replication activity is only slightly affected. Treatment of pure EF-Tu with kirromycin, however, prevents it from functioning in the renaturation of Qbeta replicase. This antibiotic is not effective against the EF-Tu-Ts complex in the reconstitution assay. Kirromycin at the relatively high concentration used here is found to prevent the formation of the EF-Tu-Ts complex. GDP, which binds to EF-Tu and inhibits formation of the complex with EF-Ts, also inhibits renaturation of Qbeta replicase. It is suggested that the EF-Tu-Ts complex, rather than the individual polypeptides, functions in the renaturation of Qbeta replicase and that the kirromycin and GDP act by preventing formation of this complex."} {"id": "PMID:1262343", "title": "Cooperativity in the dissociation of nitric oxide from hemoglobin.", "content": "The dissociation of nitric oxide from hemoglobin, from isolated subunits of hemoglobin, and from myoglobin has been studied using dithionite to remove free nitric oxide. The reduction of nitric oxide by dithionite has a rate of 1.4 X 10(3) M-1 S-1 at 20 degrees in 0.05 M phosphate, pH 7.0, which is small compared with the rate of recombination of hemoglobin with nitric oxide (25 X 10(6) M-1 S-1 (Cassoly, R., and Gibson, Q. H. (1975) J. Mol. Biol. 91, 301-313). The rate of NO combination with chains and myoglobin was found to be 24 X 10(6) M-1 S-1 and 17 X 10(6) M-1 S-1, respectively. Hence, the observed progress curve of the dissociation of nitric oxide is dependent upon the dithionite concentration and the total heme concentration. Addition of excess carbon monoxide to the dissociation mixture reduces the free heme yielding a single exponential process for chains and for myoglobin which is dithionite and heme concentration independent over a wide range of concentrations. The rates of dissociation of nitric oxide from alpha chains, from beta chains, and from myoglobin are 4.6 X 10(-5) S-1, 2.2 X 10(-5) S-1, and 1.2 X 10(4) S-1, respectively, both in the presence and in the absence of carbon monoxide at 20 degrees in 0.05 M phosphate, pH 7.0. Analogous heme and dithionite concentration dependence is found for the dissociation of nitric oxide from tetrameric hemoglobin. The reaction is cooperative, the intrinsic rate constants for the dissociation of the 1st and 4th molecules of NO differing about 100-fold. With hemoglobin, replacement of NO by CO at neutral pH is biphasic in phosphate buffers. The rate of the slow phase is 1 X 10(-5) S-1 and is independent of pH. The amplitude of the fast phase increases with lowering of pH. By analogy with the treatment of the HbCO + NO reaction given by Salhany et al. (Salhany, J.M., Ogawa, S., and Shulman, R.G. (1975) Biochemistry 14, 2180-2190), the fast phase is attributed to the dissociation of NO from T state molecules and the slow phase to dissociation from R state molecules. Analysis of the data gives a pH-independent value of 0.01 for the allosteric constant c (c = Kr/Kt where Kr and Kt are the dissociation constants for NO from the R and T states, respectively) and pH-dependent values of L (2.5 X 10(7) at pH 7 in 0.05 M phosphate buffer). The value of c is considerably greater than that for O2 and CO. Studies of the difference spectrum induced in the Soret region by inositol hexaphosphate are also reported. This spectrum does not arise directly from the change of conformation between R and T states. The results show that if the equilibrium binding curve for NO could be determined experimentally, it would show cooperativity with Hill's n at 50% saturation of about 1.6.", "contents": "Cooperativity in the dissociation of nitric oxide from hemoglobin. The dissociation of nitric oxide from hemoglobin, from isolated subunits of hemoglobin, and from myoglobin has been studied using dithionite to remove free nitric oxide. The reduction of nitric oxide by dithionite has a rate of 1.4 X 10(3) M-1 S-1 at 20 degrees in 0.05 M phosphate, pH 7.0, which is small compared with the rate of recombination of hemoglobin with nitric oxide (25 X 10(6) M-1 S-1 (Cassoly, R., and Gibson, Q. H. (1975) J. Mol. Biol. 91, 301-313). The rate of NO combination with chains and myoglobin was found to be 24 X 10(6) M-1 S-1 and 17 X 10(6) M-1 S-1, respectively. Hence, the observed progress curve of the dissociation of nitric oxide is dependent upon the dithionite concentration and the total heme concentration. Addition of excess carbon monoxide to the dissociation mixture reduces the free heme yielding a single exponential process for chains and for myoglobin which is dithionite and heme concentration independent over a wide range of concentrations. The rates of dissociation of nitric oxide from alpha chains, from beta chains, and from myoglobin are 4.6 X 10(-5) S-1, 2.2 X 10(-5) S-1, and 1.2 X 10(4) S-1, respectively, both in the presence and in the absence of carbon monoxide at 20 degrees in 0.05 M phosphate, pH 7.0. Analogous heme and dithionite concentration dependence is found for the dissociation of nitric oxide from tetrameric hemoglobin. The reaction is cooperative, the intrinsic rate constants for the dissociation of the 1st and 4th molecules of NO differing about 100-fold. With hemoglobin, replacement of NO by CO at neutral pH is biphasic in phosphate buffers. The rate of the slow phase is 1 X 10(-5) S-1 and is independent of pH. The amplitude of the fast phase increases with lowering of pH. By analogy with the treatment of the HbCO + NO reaction given by Salhany et al. (Salhany, J.M., Ogawa, S., and Shulman, R.G. (1975) Biochemistry 14, 2180-2190), the fast phase is attributed to the dissociation of NO from T state molecules and the slow phase to dissociation from R state molecules. Analysis of the data gives a pH-independent value of 0.01 for the allosteric constant c (c = Kr/Kt where Kr and Kt are the dissociation constants for NO from the R and T states, respectively) and pH-dependent values of L (2.5 X 10(7) at pH 7 in 0.05 M phosphate buffer). The value of c is considerably greater than that for O2 and CO. Studies of the difference spectrum induced in the Soret region by inositol hexaphosphate are also reported. This spectrum does not arise directly from the change of conformation between R and T states. The results show that if the equilibrium binding curve for NO could be determined experimentally, it would show cooperativity with Hill's n at 50% saturation of about 1.6."} {"id": "PMID:1262344", "title": "Polyamine transport and metabolism in mouse mammary gland. General properties and hormonal regulation.", "content": "Mouse mammary gland has been shown to possess a transport system for spermidine, spermine, and putrescine. The uptake system for sperimidine, as studied in detail on mammary explants in culture is a time-dependent, energy-requiring process which can be stimulated by insulin and prolactin. The stimulatory effect of insulin involves both enhancement of Vmax for spermidine influx and prevention of efflux of the polyamine, whereas prolactin, in the presence of insulin, elicits a greater increase in Vmax for spermidine. Studies are also reported on the effects of temperature, concentration, and various inhibitors on this system. The accumulated spermidine exists virtually in an unchanged form with little metabolic conversion to either spermine or putrescine or to its conjugated form. In contrast, spermine and putrescine, both of which are also taken up by mammary explants, undergo metabolic conversion to spermidine.", "contents": "Polyamine transport and metabolism in mouse mammary gland. General properties and hormonal regulation. Mouse mammary gland has been shown to possess a transport system for spermidine, spermine, and putrescine. The uptake system for sperimidine, as studied in detail on mammary explants in culture is a time-dependent, energy-requiring process which can be stimulated by insulin and prolactin. The stimulatory effect of insulin involves both enhancement of Vmax for spermidine influx and prevention of efflux of the polyamine, whereas prolactin, in the presence of insulin, elicits a greater increase in Vmax for spermidine. Studies are also reported on the effects of temperature, concentration, and various inhibitors on this system. The accumulated spermidine exists virtually in an unchanged form with little metabolic conversion to either spermine or putrescine or to its conjugated form. In contrast, spermine and putrescine, both of which are also taken up by mammary explants, undergo metabolic conversion to spermidine."} {"id": "PMID:1262345", "title": "Cell-free synthesis of a large translation product of prolactin messenger RNA.", "content": "RNA prepared from rat anterior pituitaries or from prolactin-secreting pituitary tumors has been shown to direct the synthesis of a large form of prolactin in a cell-free system derived from wheat germ. Immunoprecipitation of cell-free reactions demonstrated the synthesis of a product which was recognized by a specific antiprolactin antisera. Analysis of the immunoprecipitate on sodium dodecyl sulfate containing polyacrylamide gels suggested that the cell-free product has a molecular weight of approximately 28,000 compared to 22,500 for prolactin. RNA prepared by completely different techniques from rat pituitary and a pituitary tumor resulted in identical large translation products. Translation of tumor RNA in a cell-free system from Krebs ascites cells also resulted in a similar large product. The identity of the cell-free product as prolactin was confirmed by comparing peptides derived from the cell-free product and prolactin. The results of these studies suggest that prolactin messenger RNA directs the cell-free synthesis of a product which contains the amino acid sequence of prolactin but which has an addition at one or both ends of the molecule.", "contents": "Cell-free synthesis of a large translation product of prolactin messenger RNA. RNA prepared from rat anterior pituitaries or from prolactin-secreting pituitary tumors has been shown to direct the synthesis of a large form of prolactin in a cell-free system derived from wheat germ. Immunoprecipitation of cell-free reactions demonstrated the synthesis of a product which was recognized by a specific antiprolactin antisera. Analysis of the immunoprecipitate on sodium dodecyl sulfate containing polyacrylamide gels suggested that the cell-free product has a molecular weight of approximately 28,000 compared to 22,500 for prolactin. RNA prepared by completely different techniques from rat pituitary and a pituitary tumor resulted in identical large translation products. Translation of tumor RNA in a cell-free system from Krebs ascites cells also resulted in a similar large product. The identity of the cell-free product as prolactin was confirmed by comparing peptides derived from the cell-free product and prolactin. The results of these studies suggest that prolactin messenger RNA directs the cell-free synthesis of a product which contains the amino acid sequence of prolactin but which has an addition at one or both ends of the molecule."} {"id": "PMID:1262346", "title": "Purification and properties of the nuclease inhibitor of Aspergillus oryzae and kinetics of its interaction with crystalline nuclease O.", "content": "A nuclease inhibitor found in the mycelia of Aspergillus oryzae has been purified 158,000-fold by ammonium sulfate precipitation, chromatography on Sephadex G-75, DEAE-Sephadex A-50 and Bio-Gel p-60 columns, preparative disc electrophoresis on acrylamide gel, and electrofocusing in ampholite. The purified inhibitor is nearly homogeneous as judged by disc electrophoresis. It shows a typical ultraviolet absorption curve for protein, and the inhibitory activity is inactivated by chymotrypsin. The inhibitor and nuclease O (EC 3.1.4.9, a crystalline enzyme from the mycelia of the same organism) form a stable enzyme inhibitor complex. The molecular weights of nuclease O, the inhibitor and the enzyme inhibitor complex are estimated to be 46,000, 22,000 and 73,000 respectively, by Sephadex G-100 gel filtration. The isoelectric points of the enzyme and the inhibitor are 10.0 and 4.09, respectively, as determined by electrofocusing in ampholite. The inhibition is noncompetitive, and the inhibitor constant (K1) is 3.2 X 10(-12) M, whereas the Michaelis constant (Km) for DNA is 2.2 X 10(-8) M. The inactive enzyme-inhibitor complex is reactivated by chymotrypsin through inactivation of the inhibitor. The reactivated enzyme can be inactivated again by the inhibitor, which shows that desensitization of the enzyme does not occur by the action of chymotrypsin.", "contents": "Purification and properties of the nuclease inhibitor of Aspergillus oryzae and kinetics of its interaction with crystalline nuclease O. A nuclease inhibitor found in the mycelia of Aspergillus oryzae has been purified 158,000-fold by ammonium sulfate precipitation, chromatography on Sephadex G-75, DEAE-Sephadex A-50 and Bio-Gel p-60 columns, preparative disc electrophoresis on acrylamide gel, and electrofocusing in ampholite. The purified inhibitor is nearly homogeneous as judged by disc electrophoresis. It shows a typical ultraviolet absorption curve for protein, and the inhibitory activity is inactivated by chymotrypsin. The inhibitor and nuclease O (EC 3.1.4.9, a crystalline enzyme from the mycelia of the same organism) form a stable enzyme inhibitor complex. The molecular weights of nuclease O, the inhibitor and the enzyme inhibitor complex are estimated to be 46,000, 22,000 and 73,000 respectively, by Sephadex G-100 gel filtration. The isoelectric points of the enzyme and the inhibitor are 10.0 and 4.09, respectively, as determined by electrofocusing in ampholite. The inhibition is noncompetitive, and the inhibitor constant (K1) is 3.2 X 10(-12) M, whereas the Michaelis constant (Km) for DNA is 2.2 X 10(-8) M. The inactive enzyme-inhibitor complex is reactivated by chymotrypsin through inactivation of the inhibitor. The reactivated enzyme can be inactivated again by the inhibitor, which shows that desensitization of the enzyme does not occur by the action of chymotrypsin."} {"id": "PMID:1262347", "title": "Chemical cross-linking of myosin. Disposition of the globular heads.", "content": "The interaction of a series of bifunctional reagents with skeletal muscle myosin has been studied. In the di-imido ester series dimethylmalonimidate failed to generate any cross-linked species, whereas the adipic and higher analogues gave dimers of myosin heavy chains. Analysis of free amino groups after reaction with these reagents and with the reducible species dimethyldithiobis(propionimidate) showed that no more than two to three cross-links per molecule were introduced. By contrast, the bifunctional reducible acylating agent, dithiobis(succinimidylpropionate), reacted with annihilation of about 10% of the amino groups under mild conditions that precluded the formation of intermolecularly linked species. Digestion of the intramolecularly cross-linked myosin with papain, followed by analysis of the fragments by gel electrophoresis, revealed extensive cross-linking between the globular heads of the myosin molecules. The subfragment 1 dimers regenerated subfragment 1 on reduction, as shown by the electrophoretic mobility and amino acid analysis. The extent of cross-linking, and therefore presumably the average relative orientation or freedom of the two heads, was unaffected by the addition of ADP and calcium ions. The internally cross-linked myosin retains practically its full calcium-activated adenosine triphosphatase activity, but in contrast to native myosin is soluble even at very low ionic strength. Circular dichroism measurements show that the alpha helical conformation is undisturbed in cross-linked myosin, but the sedimentation coefficient is considerably higher than that of the native protein, possibly due to freezing of the heads in a \"closed\" configuration. The light chaiins are not cross-linked to the heavy chains, except under extreme conditions that leads to intermolecular cross-linking and inactivation. The presence of calcium ions protects dithiobisnitrobenzoate light chains against degradation by papain.", "contents": "Chemical cross-linking of myosin. Disposition of the globular heads. The interaction of a series of bifunctional reagents with skeletal muscle myosin has been studied. In the di-imido ester series dimethylmalonimidate failed to generate any cross-linked species, whereas the adipic and higher analogues gave dimers of myosin heavy chains. Analysis of free amino groups after reaction with these reagents and with the reducible species dimethyldithiobis(propionimidate) showed that no more than two to three cross-links per molecule were introduced. By contrast, the bifunctional reducible acylating agent, dithiobis(succinimidylpropionate), reacted with annihilation of about 10% of the amino groups under mild conditions that precluded the formation of intermolecularly linked species. Digestion of the intramolecularly cross-linked myosin with papain, followed by analysis of the fragments by gel electrophoresis, revealed extensive cross-linking between the globular heads of the myosin molecules. The subfragment 1 dimers regenerated subfragment 1 on reduction, as shown by the electrophoretic mobility and amino acid analysis. The extent of cross-linking, and therefore presumably the average relative orientation or freedom of the two heads, was unaffected by the addition of ADP and calcium ions. The internally cross-linked myosin retains practically its full calcium-activated adenosine triphosphatase activity, but in contrast to native myosin is soluble even at very low ionic strength. Circular dichroism measurements show that the alpha helical conformation is undisturbed in cross-linked myosin, but the sedimentation coefficient is considerably higher than that of the native protein, possibly due to freezing of the heads in a \"closed\" configuration. The light chaiins are not cross-linked to the heavy chains, except under extreme conditions that leads to intermolecular cross-linking and inactivation. The presence of calcium ions protects dithiobisnitrobenzoate light chains against degradation by papain."} {"id": "PMID:1262348", "title": "Heterogeneity of cytochrome P-450 in rat testis microsomes.", "content": "Cytochrome P-450 appears to be a component of the steroid-coverting enzymes, 17alpha-hydroxylase and 17,20-lyase, which catalyze sequential steps in sex hormone synthesis. Further evidence indicates that the steroid substrates of these enzymes bind to cytochrome P-450 during catalysis. The present report deals with the problem of whether a single form of cytochrome P-450 mediates both enzyme reactions or whether two enzymes are involved. Both activities are competitively inhibited by a number of the same inhibitors. Because K1 values of competitive inhibitors are dissociated constants, and thus a property of the cytochrome, different magnitudes of K1, determined for the same inhibitor with each enzyme, are consistent with the participation of more than one form of cytochrome P-450. Differences in the K1 values were found to be statistically significant and varied from 3- to 10-fold. Two competitive inhibitors retarded velocities with one reaction but not the other. In addition, the enzyme activities were markedly different in their sensitivity to carbon monoxide inhibition. The conclusion based on these two lines of evidence is that separate enzymes and different forms of cytochrome P-450 are involved in each reaction.", "contents": "Heterogeneity of cytochrome P-450 in rat testis microsomes. Cytochrome P-450 appears to be a component of the steroid-coverting enzymes, 17alpha-hydroxylase and 17,20-lyase, which catalyze sequential steps in sex hormone synthesis. Further evidence indicates that the steroid substrates of these enzymes bind to cytochrome P-450 during catalysis. The present report deals with the problem of whether a single form of cytochrome P-450 mediates both enzyme reactions or whether two enzymes are involved. Both activities are competitively inhibited by a number of the same inhibitors. Because K1 values of competitive inhibitors are dissociated constants, and thus a property of the cytochrome, different magnitudes of K1, determined for the same inhibitor with each enzyme, are consistent with the participation of more than one form of cytochrome P-450. Differences in the K1 values were found to be statistically significant and varied from 3- to 10-fold. Two competitive inhibitors retarded velocities with one reaction but not the other. In addition, the enzyme activities were markedly different in their sensitivity to carbon monoxide inhibition. The conclusion based on these two lines of evidence is that separate enzymes and different forms of cytochrome P-450 are involved in each reaction."} {"id": "PMID:1262349", "title": "Cell-free synthesis of a prolactin precursor directed by mRNA from cultured rat pituitary cells.", "content": "Polyadenylate-rich mRNA extracted from an established line of functional rat pituitary tumor cells (GH3) which respond to the addition of thyrotropin-releasing factor with the synthesis and secretion of prolactin directed cell-free synthesis using a cell-free protein-synthesizing system derived from wheat embryos. The products of translation, when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, did not include any protein co-migrating with rat prolactin. One prominent protein synthesized was precipitated using anti-prolactin antiserum. This protein was larger than the prolactin standard with an apparent molecular weight of 28,000 +/- 2,000. Addition of a GH3 cell extract to the translation system resulted in the appearance of a protein which co-migrated with rat prolactin and was immunoprecipitated with anti-rat prolactin antiserum. Addition of thyrotropin-releasing factor to spinner cultures of GH3 cells for 48 to 72 hours increased de novo prolactin biosynthesis. Levels of mRNA coding for prolactin determined by translation of total mRNA and quantitation of preprolactin synthesized were stimulated 3- to 6-fold relative to the levels in control cultures, suggesting that regulation of prolactin synthesis was accomplished, at least in part, at a transcriptional level.", "contents": "Cell-free synthesis of a prolactin precursor directed by mRNA from cultured rat pituitary cells. Polyadenylate-rich mRNA extracted from an established line of functional rat pituitary tumor cells (GH3) which respond to the addition of thyrotropin-releasing factor with the synthesis and secretion of prolactin directed cell-free synthesis using a cell-free protein-synthesizing system derived from wheat embryos. The products of translation, when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography, did not include any protein co-migrating with rat prolactin. One prominent protein synthesized was precipitated using anti-prolactin antiserum. This protein was larger than the prolactin standard with an apparent molecular weight of 28,000 +/- 2,000. Addition of a GH3 cell extract to the translation system resulted in the appearance of a protein which co-migrated with rat prolactin and was immunoprecipitated with anti-rat prolactin antiserum. Addition of thyrotropin-releasing factor to spinner cultures of GH3 cells for 48 to 72 hours increased de novo prolactin biosynthesis. Levels of mRNA coding for prolactin determined by translation of total mRNA and quantitation of preprolactin synthesized were stimulated 3- to 6-fold relative to the levels in control cultures, suggesting that regulation of prolactin synthesis was accomplished, at least in part, at a transcriptional level."} {"id": "PMID:1262350", "title": "Protein synthesis in plant leaf tissue. The sites of synthesis of the major proteins.", "content": "Protein synthesis in the leaves of green pea seedlings (Pisum sativum) is examined by short term labeling with [35S]methionine and autoradiography of the labeled proteins after fractionation by sodium dodecyl sulfate-acrylamide gel electrophoresis. The two subunits of ribulose-1,5-diphosphate carboxylase and the chloroplast lamellar proteins are identified as the major proteins being synthesized. Three protein chlorophyll complexes are characterized by sodium dodecyl sulfate-acrylamide gel electrophoresis; all three complexes are disrupted by heating to 100 degrees in sodium dodecyl sulfate solution. Studies with inhibitors of protein synthesis indicate that the large subunit of ribulos-1,5-diphosphate carboxylase is synthesized in the chloroplast, in contrast to the majority of the soluble proteins, including the small subunit of ribulose-1,5-diphosphate carboxylase, which is synthesized in the cytoplasm. PII protein, the major lamellar protein associated with photosystem II, is also synthesized on cytoplasmic ribosomes. However, many of the lamellar proteins are synthesized within the chloroplast. Integration into the lamellar system of at least one of the chloroplast-synthesized proteins is shown to be dependent on cytoplasmic protein synthesis.", "contents": "Protein synthesis in plant leaf tissue. The sites of synthesis of the major proteins. Protein synthesis in the leaves of green pea seedlings (Pisum sativum) is examined by short term labeling with [35S]methionine and autoradiography of the labeled proteins after fractionation by sodium dodecyl sulfate-acrylamide gel electrophoresis. The two subunits of ribulose-1,5-diphosphate carboxylase and the chloroplast lamellar proteins are identified as the major proteins being synthesized. Three protein chlorophyll complexes are characterized by sodium dodecyl sulfate-acrylamide gel electrophoresis; all three complexes are disrupted by heating to 100 degrees in sodium dodecyl sulfate solution. Studies with inhibitors of protein synthesis indicate that the large subunit of ribulos-1,5-diphosphate carboxylase is synthesized in the chloroplast, in contrast to the majority of the soluble proteins, including the small subunit of ribulose-1,5-diphosphate carboxylase, which is synthesized in the cytoplasm. PII protein, the major lamellar protein associated with photosystem II, is also synthesized on cytoplasmic ribosomes. However, many of the lamellar proteins are synthesized within the chloroplast. Integration into the lamellar system of at least one of the chloroplast-synthesized proteins is shown to be dependent on cytoplasmic protein synthesis."} {"id": "PMID:1262364", "title": "Thoracolumbar scoliosis in cerebral palsy. Results of surgical treatment.", "content": "Of 294 patients with cerebral palsy seen from 1960 to 1972, forty-two had clinically significant lumbar and thoracolumbar scoliosis (31 to 135 degrees) and thirty-three were treated by spine surgery: ten by Harrington instrumentation and posterior spine fusion, eighteen by the Dwyer procedure and anterior fusion, and five by a two-stage combined anterior and posterior fusion. Evaluation of the results after eighteen to sixty-eight months showed: relief of pain in seventeen cases, improved sitting tolerance in seventeen, less nursing care needed in three, less equipment required in six, ability to use equipment providing more function in three, placement in a facility where less care was required in two, and improved eating patterns in two. Only the combined procedure appeared to give adequate correction and a low incidence of pseudarthrosis.", "contents": "Thoracolumbar scoliosis in cerebral palsy. Results of surgical treatment. Of 294 patients with cerebral palsy seen from 1960 to 1972, forty-two had clinically significant lumbar and thoracolumbar scoliosis (31 to 135 degrees) and thirty-three were treated by spine surgery: ten by Harrington instrumentation and posterior spine fusion, eighteen by the Dwyer procedure and anterior fusion, and five by a two-stage combined anterior and posterior fusion. Evaluation of the results after eighteen to sixty-eight months showed: relief of pain in seventeen cases, improved sitting tolerance in seventeen, less nursing care needed in three, less equipment required in six, ability to use equipment providing more function in three, placement in a facility where less care was required in two, and improved eating patterns in two. Only the combined procedure appeared to give adequate correction and a low incidence of pseudarthrosis."} {"id": "PMID:1262365", "title": "A clinical study of the Batchelor subtalar arthrodesis.", "content": "Results of subtalar arthrodesis performed by the Batchelor method were reviewed in thirty-four feet of twenty-two patients who had an average follow-up of thirty-nine months. The pseudarthrosis rate was 41 per cent, which is considerably higher than that reported for the Grice extra-articular arthrodesis. Three feet had a recurrence of deformity later than one year postoperatively. Two factors seemed related to the high incidence of pseudarthrosis: the parallelism of the axis of the graft to the axis of the subtalar joint and the cortical nature of the graft.", "contents": "A clinical study of the Batchelor subtalar arthrodesis. Results of subtalar arthrodesis performed by the Batchelor method were reviewed in thirty-four feet of twenty-two patients who had an average follow-up of thirty-nine months. The pseudarthrosis rate was 41 per cent, which is considerably higher than that reported for the Grice extra-articular arthrodesis. Three feet had a recurrence of deformity later than one year postoperatively. Two factors seemed related to the high incidence of pseudarthrosis: the parallelism of the axis of the graft to the axis of the subtalar joint and the cortical nature of the graft."} {"id": "PMID:1262366", "title": "Tension studies of human knee ligaments. Yield point, ultimate failure, and disruption of the cruciate and tibial collateral ligaments.", "content": "Ultimate failure strengths of human tibial collateral and anterior and posterior cruciate ligaments were determined at two different loading rates (12.5 and fifty centimeters per minute) using an Instron Tension Analyzer. The posterior cruciate ligament was significantly stronger than the tibial collateral and anterior cruciate ligaments, which were of equal strength. At ultimate failure the ligaments were intact macroscopically but electron microscopy revealed widespread disruption of the collagen fibrils. Only after further application of stress did actual macroscopic disruption occur, suggesting that microscopic failure of the collagen fibrils in grossly intact ligaments may be a significant cause of clinical instability.", "contents": "Tension studies of human knee ligaments. Yield point, ultimate failure, and disruption of the cruciate and tibial collateral ligaments. Ultimate failure strengths of human tibial collateral and anterior and posterior cruciate ligaments were determined at two different loading rates (12.5 and fifty centimeters per minute) using an Instron Tension Analyzer. The posterior cruciate ligament was significantly stronger than the tibial collateral and anterior cruciate ligaments, which were of equal strength. At ultimate failure the ligaments were intact macroscopically but electron microscopy revealed widespread disruption of the collagen fibrils. Only after further application of stress did actual macroscopic disruption occur, suggesting that microscopic failure of the collagen fibrils in grossly intact ligaments may be a significant cause of clinical instability."} {"id": "PMID:1262367", "title": "Changes in tibiotalar area of contact caused by lateral talar shift.", "content": "A carbon black transference technique was used to determine the contact area in twenty-three dissected tibiotalar articulations, with the talus in neutral position and displaced one, two, four, and six millimeters laterally. The greatest reduction in contact area occurred during the initial one millimeter of lateral displacement, the average reduction being 42 per cent. With further lateral displacement of the talus the contact area was progressively reduced but the rate of change for each increment of shift was less marked.", "contents": "Changes in tibiotalar area of contact caused by lateral talar shift. A carbon black transference technique was used to determine the contact area in twenty-three dissected tibiotalar articulations, with the talus in neutral position and displaced one, two, four, and six millimeters laterally. The greatest reduction in contact area occurred during the initial one millimeter of lateral displacement, the average reduction being 42 per cent. With further lateral displacement of the talus the contact area was progressively reduced but the rate of change for each increment of shift was less marked."} {"id": "PMID:1262368", "title": "The below-the-knee amputation for vascular disease.", "content": "Of 190 consecutive patients with below-the-knee amputation done for diabetic or arteriosclerotic vascular disease, 167 were successfully fitted with a prosthesis and used the prosthesis in some or all of the activities of daily living. The surgical failure rate was 4.2 per cent; only eight patients required surgical revision to a higher level of amputation. The technique of rigid plaster dressing followed by delayed application of a plaster cast and pylon was not detrimental to wound healing and did not increase the interval between surgery and the use of the prosthesis, nor did it depress the eventual level of function. When compared with our own previous experience with other flaps, the long posterior flap offered a significant advantage in healing rate.", "contents": "The below-the-knee amputation for vascular disease. Of 190 consecutive patients with below-the-knee amputation done for diabetic or arteriosclerotic vascular disease, 167 were successfully fitted with a prosthesis and used the prosthesis in some or all of the activities of daily living. The surgical failure rate was 4.2 per cent; only eight patients required surgical revision to a higher level of amputation. The technique of rigid plaster dressing followed by delayed application of a plaster cast and pylon was not detrimental to wound healing and did not increase the interval between surgery and the use of the prosthesis, nor did it depress the eventual level of function. When compared with our own previous experience with other flaps, the long posterior flap offered a significant advantage in healing rate."} {"id": "PMID:1262369", "title": "Management of painful neuromas in the hand.", "content": "A new treatment for painful neuromas in the hand was used on thirtty-three patients. Fifteen of them were partial amputees and the others had unrepairable lesions. The treatment was transfer of the stumps to an unscarred site where the neuroma would not be under pressure when the hand was used. Excellent results were achieved in 82 per cent of patients.", "contents": "Management of painful neuromas in the hand. A new treatment for painful neuromas in the hand was used on thirtty-three patients. Fifteen of them were partial amputees and the others had unrepairable lesions. The treatment was transfer of the stumps to an unscarred site where the neuroma would not be under pressure when the hand was used. Excellent results were achieved in 82 per cent of patients."} {"id": "PMID:1262370", "title": "Treatment of Kienb\u00f6ck's disease using a silicone rubber implant.", "content": "Ten patients with Kienb\u00f6ck's disease treated by resection and replacement with a silicone rubber implant through a volar approach were reviewed after follow-up ranging from twenty-four to thirty months. The results were good in seven and unsatisfactory in three: two patients had volar dislocation of the implant and one, median-nerve paresthesias of unexplained origin.", "contents": "Treatment of Kienb\u00f6ck's disease using a silicone rubber implant. Ten patients with Kienb\u00f6ck's disease treated by resection and replacement with a silicone rubber implant through a volar approach were reviewed after follow-up ranging from twenty-four to thirty months. The results were good in seven and unsatisfactory in three: two patients had volar dislocation of the implant and one, median-nerve paresthesias of unexplained origin."} {"id": "PMID:1262371", "title": "The sub-deltoid approach to the metaphyseal region of the humerus.", "content": "In a new surgical approach to the proximal part of the humerus, used in eighteen patients, the distal part of the tendon of the deltoid muscle was divided and the whole muscle was lifted up to give an excellent view of the proximal one-third of the diaphysis, the metaphysis, the surgical neck, and both tuberosities of the humerus. The exposure allowed visualization and protection of the axillary nerve. Postoperatively the deltoid remained functional and only the preoperative condition of the joint seemed to prevent full recovery of function of the muscles in a few patients.", "contents": "The sub-deltoid approach to the metaphyseal region of the humerus. In a new surgical approach to the proximal part of the humerus, used in eighteen patients, the distal part of the tendon of the deltoid muscle was divided and the whole muscle was lifted up to give an excellent view of the proximal one-third of the diaphysis, the metaphysis, the surgical neck, and both tuberosities of the humerus. The exposure allowed visualization and protection of the axillary nerve. Postoperatively the deltoid remained functional and only the preoperative condition of the joint seemed to prevent full recovery of function of the muscles in a few patients."} {"id": "PMID:1262372", "title": "Treatment of Dupuytren's contracture. Long-term results after fasciotomy and fascial excision.", "content": "Of 359 hands treated surgically for Dupuytren's contracture, 135 were available for study after two years or more, often because of recurrence. Of the sixty-five hands treated by excision of the involved fascia (subtotal fasciectomy), 63 per cent had recurrences in the area operated on but only 15 per cent had sufficient deformity to warrant another operation. Of the forty-one hands treated by palmar fasciotomy, 43 per cent had recurrent deformities severe enough to warrant further surgical treatment. After palmar fasciotomy, improvement at the metacarpohalangeal joint persisted; but, as expected, the deformity at the proximal interphalangeal joint progressed just as it did in an untreated control group. The average postoperative period of disability was fifty-nine days after fasciectomy and twenty-one days after fasciotomy. Stiffness and hematoma occurred after fasciectomy but were not observed after fasciotomy. A digital nerve was severed during one fasciotomy and one fasciectomy. Excision of the involved fascia, therefore, gave the best long-term results but was associated with a higher incidence of postoperative complications.", "contents": "Treatment of Dupuytren's contracture. Long-term results after fasciotomy and fascial excision. Of 359 hands treated surgically for Dupuytren's contracture, 135 were available for study after two years or more, often because of recurrence. Of the sixty-five hands treated by excision of the involved fascia (subtotal fasciectomy), 63 per cent had recurrences in the area operated on but only 15 per cent had sufficient deformity to warrant another operation. Of the forty-one hands treated by palmar fasciotomy, 43 per cent had recurrent deformities severe enough to warrant further surgical treatment. After palmar fasciotomy, improvement at the metacarpohalangeal joint persisted; but, as expected, the deformity at the proximal interphalangeal joint progressed just as it did in an untreated control group. The average postoperative period of disability was fifty-nine days after fasciectomy and twenty-one days after fasciotomy. Stiffness and hematoma occurred after fasciectomy but were not observed after fasciotomy. A digital nerve was severed during one fasciotomy and one fasciectomy. Excision of the involved fascia, therefore, gave the best long-term results but was associated with a higher incidence of postoperative complications."} {"id": "PMID:1262373", "title": "Suppurative arthritis of the hip in children.", "content": "Of thirty-seven children treated at the Mayo Clinic for suppurative arthritis of the hip and followed for at least one year (average, 8.3 years), nineteen had a satisfactory result and eighteen, an unsatisfactory result. An analysis of the records of the thirty-seven children revealed the following: (1) duration of symptoms was the most important prognostic feature, there being no unsatisfactory results if treatment was instituted less than four days after onset of symptoms; (2) fourteen of sixteen patients with associated osteomyelitis and six of eight with so-called penicillin-resistant Staphylococcus aureus had unsatisfactory results; (3) if symptoms had been present for more than ten days or if there was osteomyelitis, at least two weeks of parenteral antibiotics with arthrotomy and continuous irrigation offered the best prognosis; and (4) the prognosis has improved in recent years, possibly due to a move vigorous policy of early arthrotomy.", "contents": "Suppurative arthritis of the hip in children. Of thirty-seven children treated at the Mayo Clinic for suppurative arthritis of the hip and followed for at least one year (average, 8.3 years), nineteen had a satisfactory result and eighteen, an unsatisfactory result. An analysis of the records of the thirty-seven children revealed the following: (1) duration of symptoms was the most important prognostic feature, there being no unsatisfactory results if treatment was instituted less than four days after onset of symptoms; (2) fourteen of sixteen patients with associated osteomyelitis and six of eight with so-called penicillin-resistant Staphylococcus aureus had unsatisfactory results; (3) if symptoms had been present for more than ten days or if there was osteomyelitis, at least two weeks of parenteral antibiotics with arthrotomy and continuous irrigation offered the best prognosis; and (4) the prognosis has improved in recent years, possibly due to a move vigorous policy of early arthrotomy."} {"id": "PMID:1262374", "title": "Lavage of septic joints in rabbits: effects of chondrolysis.", "content": "Septic joints were produced in rabbits which were then treated with systemic procaine penicillin. One group of animals also had surgical lavage at four and seven days after bacterial inoculation. In the infected joints there was a significant loss of hexosamine by five days and of collagen by nine days. Lavage delayed the loss of collagen.", "contents": "Lavage of septic joints in rabbits: effects of chondrolysis. Septic joints were produced in rabbits which were then treated with systemic procaine penicillin. One group of animals also had surgical lavage at four and seven days after bacterial inoculation. In the infected joints there was a significant loss of hexosamine by five days and of collagen by nine days. Lavage delayed the loss of collagen."} {"id": "PMID:1262375", "title": "Spine fusion for atlanto-axial instability.", "content": "A follow-up study was done on fifty-seven spine fusions for atlanto-axial instability, classified as Type I - deficient odontoid (twenty-eight patients), Type II - deficient ligaments (twenty-three patients), and Type III - rotatory fixation (six patients). The average age of the patients at the time of the fusion was thirty years, and half had had significant trauma. Symptoms had been present for an average of 12.3 months before fusion. Preoperatively pain was the predominant complaint in twenty-nine; neurological complaints, in twenty-four; and instability in the rest. Of the forty-six Gallie fusions, there was one non-union and of the eleven occipitocervical fusions, two non-unions. Follow-up averaging 4.2 years revealed resolution of symptoms in almost all patients.", "contents": "Spine fusion for atlanto-axial instability. A follow-up study was done on fifty-seven spine fusions for atlanto-axial instability, classified as Type I - deficient odontoid (twenty-eight patients), Type II - deficient ligaments (twenty-three patients), and Type III - rotatory fixation (six patients). The average age of the patients at the time of the fusion was thirty years, and half had had significant trauma. Symptoms had been present for an average of 12.3 months before fusion. Preoperatively pain was the predominant complaint in twenty-nine; neurological complaints, in twenty-four; and instability in the rest. Of the forty-six Gallie fusions, there was one non-union and of the eleven occipitocervical fusions, two non-unions. Follow-up averaging 4.2 years revealed resolution of symptoms in almost all patients."} {"id": "PMID:1262384", "title": "Intracardiac repair of isolated ventricular septal defects below two years of age.", "content": "Experience with closure of ventricular septal defect in 32 patients under two years is presented. Indications for correction were: (a) intractable heart failure; (b) persistence of progression of pulmonary artery hypertension; (c) failure of pulmonary artery banding; (d) elective closure after banding. In all but one case, the correction was done under the surface induced deep hypothermia with limited cardiopulmonary bypass and total circulatory arrest. Mortality and morbidity of the pulmonary artery banding procedure and of early closure discussed. For the corrective procedure the mortality was 3%. It is emphasized that whenever clinical or hemodynamic data support persistence or progression of pulmonary artery hypertension, corrective repair should be performed without delay. It is further suggested that pulmonary artery banding should be restricted to patients with ventricular septal defect and associated coarctation of the aorta and to patients with multiple muscular ventricular septal defects.", "contents": "Intracardiac repair of isolated ventricular septal defects below two years of age. Experience with closure of ventricular septal defect in 32 patients under two years is presented. Indications for correction were: (a) intractable heart failure; (b) persistence of progression of pulmonary artery hypertension; (c) failure of pulmonary artery banding; (d) elective closure after banding. In all but one case, the correction was done under the surface induced deep hypothermia with limited cardiopulmonary bypass and total circulatory arrest. Mortality and morbidity of the pulmonary artery banding procedure and of early closure discussed. For the corrective procedure the mortality was 3%. It is emphasized that whenever clinical or hemodynamic data support persistence or progression of pulmonary artery hypertension, corrective repair should be performed without delay. It is further suggested that pulmonary artery banding should be restricted to patients with ventricular septal defect and associated coarctation of the aorta and to patients with multiple muscular ventricular septal defects."} {"id": "PMID:1262385", "title": "Successful correction of double outlet left atrium associated with complete atrioventricular canal and l-loop double outlet right ventricle with stenosis of the pulmonary artery.", "content": "The first successful correction of \"double outlet left atrium\" was presented. This lesion is inevitably associated with complete A-V canal, and may have many associated anomalies. Technical problems concerning the total correction of this anomaly were discussed.", "contents": "Successful correction of double outlet left atrium associated with complete atrioventricular canal and l-loop double outlet right ventricle with stenosis of the pulmonary artery. The first successful correction of \"double outlet left atrium\" was presented. This lesion is inevitably associated with complete A-V canal, and may have many associated anomalies. Technical problems concerning the total correction of this anomaly were discussed."} {"id": "PMID:1262389", "title": "Action of dichlorobenzimidazole riboside on RNA synthesis in L-929 and HeLa cells.", "content": "5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) inhibits RNA synthesis in L-929 cells (mouse fibroblast line) and HeLa cells (human epitheloid carcinoma line) within 2 min of addition of the compound to the medium. By removing DRB from the medium, the inhibition is promptly and completely reversed after treatment of cells for as long as 1 h or even longer. The inhibitory effect of DRB on the overall rate of RNA synthesis is similar in L and HeLa cells and is markedly concentration-dependent in the low dose range (5-20 muM or 1.6-6.4 mug/ml), but not as higher concentrations of DRB. At a concentration of 12 muM, DRB has a highly selective inhibitory effect on the synthesis of nuclear heterogenous RNA in L cells. At higher concentrations, there is also inhibition of 45 S ribosomal precursor RNA synthesis, but at all concentrations the effect on heterogeneous RNA synthesis in L cells in considerably greater than that on preribosomal RNA synthesis. In HeLa cells, too, DRB has a selective effect on heterogeneous RNA synthesis, but quantitatively the selectivity of action is somewhat less pronounced. In both L and HeLa cells, the inhibition of synthesis of nuclear heterogeneous RNA is incomplete even at very high concentrations of DRB (150 muM). Thus, while DRB is a selective inhibitor of nuclear heterogeneous RNA synthesis, not all such RNA synthesis is sensitive to inhibition. It is proposed that messenger precursor RNA synthesis may largely be sensitive to inhibition by DRB. In short-term experiments, DRB has no effect on protein synthesis in L or HeLa cells. DRB has a slight to moderate inhibitory effect on uridine uptake into L cells and a moderate to marked effect on uptake of uridine into HeLa cells.", "contents": "Action of dichlorobenzimidazole riboside on RNA synthesis in L-929 and HeLa cells. 5,6-Dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) inhibits RNA synthesis in L-929 cells (mouse fibroblast line) and HeLa cells (human epitheloid carcinoma line) within 2 min of addition of the compound to the medium. By removing DRB from the medium, the inhibition is promptly and completely reversed after treatment of cells for as long as 1 h or even longer. The inhibitory effect of DRB on the overall rate of RNA synthesis is similar in L and HeLa cells and is markedly concentration-dependent in the low dose range (5-20 muM or 1.6-6.4 mug/ml), but not as higher concentrations of DRB. At a concentration of 12 muM, DRB has a highly selective inhibitory effect on the synthesis of nuclear heterogenous RNA in L cells. At higher concentrations, there is also inhibition of 45 S ribosomal precursor RNA synthesis, but at all concentrations the effect on heterogeneous RNA synthesis in L cells in considerably greater than that on preribosomal RNA synthesis. In HeLa cells, too, DRB has a selective effect on heterogeneous RNA synthesis, but quantitatively the selectivity of action is somewhat less pronounced. In both L and HeLa cells, the inhibition of synthesis of nuclear heterogeneous RNA is incomplete even at very high concentrations of DRB (150 muM). Thus, while DRB is a selective inhibitor of nuclear heterogeneous RNA synthesis, not all such RNA synthesis is sensitive to inhibition. It is proposed that messenger precursor RNA synthesis may largely be sensitive to inhibition by DRB. In short-term experiments, DRB has no effect on protein synthesis in L or HeLa cells. DRB has a slight to moderate inhibitory effect on uridine uptake into L cells and a moderate to marked effect on uptake of uridine into HeLa cells."} {"id": "PMID:1262386", "title": "Effect of myocardial revascularization on acute phase of myocardial infacrtion. Macroscopic, histological and electrocardiographic data.", "content": "The purpose of this study was to investigate the time during which the emergency reconstruction of the occluded coronary artery is most effective. This problem was examined from the viewpoint of the extent of reversibility of the damage to ischemic myocardial muscle, by using forty nine mongrel dogs. The surgical reconstruction of the occluded coronary artery within 6 hours after the onset of myocardial infarction was most effective. In such cases, the extent of myocardial infarction remained small in size, and the healing of necrotic myocardial muscle was hastened. Thus, the development of cardiac failure was well protected.", "contents": "Effect of myocardial revascularization on acute phase of myocardial infacrtion. Macroscopic, histological and electrocardiographic data. The purpose of this study was to investigate the time during which the emergency reconstruction of the occluded coronary artery is most effective. This problem was examined from the viewpoint of the extent of reversibility of the damage to ischemic myocardial muscle, by using forty nine mongrel dogs. The surgical reconstruction of the occluded coronary artery within 6 hours after the onset of myocardial infarction was most effective. In such cases, the extent of myocardial infarction remained small in size, and the healing of necrotic myocardial muscle was hastened. Thus, the development of cardiac failure was well protected."} {"id": "PMID:1262390", "title": "Fat body: a site of hemoglobin synthesis in Chironomus thummi (diptera).", "content": "Fourth instar larvae of Chironomus thummi were permitted to incorporate labeled amino acids and/or sigma-aminolevulinic acid (sigma-ALA) in vivo and in organ culture. The products secreted into the hemolymph or into the culture medium were examined by acrylamide gel electrophoresis. Nine electrophoretic bands can be resolved as hemoglobins without staining. When gels are sliced for scintillation counting, incorporated amino acids and sigma-ALA are shown to be associated primarily with the same nine hemoglobin bands, suggesting that hemoglobins are assembled and secreted. Staining of gels with Coomassie brilliant blue reveals that there are several bands in addition to the visible hemoglobins. These bands incorporate amino acids, but not sigma-ALA, suggesting that they are non-heme proteins. The results of culturing isolated salivary glands, gut, and fat body demonstrate that the fat body is the major site of hemoglobin synthesis and secretion. Labeled products of the gut represent about 5% of the total hemoglobins produced by the tissues, while no hemoglobins are produced by the salivary glands. Although nine hemoglobins are visibly resolved on gels, labeling techniques reveal as many as 14 hemoglobins. This is the first demonstration of hemoglobin synthesis by specific tissues in culture in an invertebrate.", "contents": "Fat body: a site of hemoglobin synthesis in Chironomus thummi (diptera). Fourth instar larvae of Chironomus thummi were permitted to incorporate labeled amino acids and/or sigma-aminolevulinic acid (sigma-ALA) in vivo and in organ culture. The products secreted into the hemolymph or into the culture medium were examined by acrylamide gel electrophoresis. Nine electrophoretic bands can be resolved as hemoglobins without staining. When gels are sliced for scintillation counting, incorporated amino acids and sigma-ALA are shown to be associated primarily with the same nine hemoglobin bands, suggesting that hemoglobins are assembled and secreted. Staining of gels with Coomassie brilliant blue reveals that there are several bands in addition to the visible hemoglobins. These bands incorporate amino acids, but not sigma-ALA, suggesting that they are non-heme proteins. The results of culturing isolated salivary glands, gut, and fat body demonstrate that the fat body is the major site of hemoglobin synthesis and secretion. Labeled products of the gut represent about 5% of the total hemoglobins produced by the tissues, while no hemoglobins are produced by the salivary glands. Although nine hemoglobins are visibly resolved on gels, labeling techniques reveal as many as 14 hemoglobins. This is the first demonstration of hemoglobin synthesis by specific tissues in culture in an invertebrate."} {"id": "PMID:1262387", "title": "False aneurysm of the left atrium after closed mitral commissurotomy: diagnosis by cineangiocardiogrpahy. Report of one case treated surgically.", "content": "A case of false aneurysm of the left atrium after closed mitral commissurotomy which was demonstrated by cineangiography is here reported. It is believed that the false aneurysm resulted from a tear of the left appendage which accidentally occurred during the surgical procedure. The diagnosis was suspected in plain chest X-ray and fluoroscopy. Angiography demonstrated the presence of a false aneurysm of the left atrium which was confirmed at surgery.", "contents": "False aneurysm of the left atrium after closed mitral commissurotomy: diagnosis by cineangiocardiogrpahy. Report of one case treated surgically. A case of false aneurysm of the left atrium after closed mitral commissurotomy which was demonstrated by cineangiography is here reported. It is believed that the false aneurysm resulted from a tear of the left appendage which accidentally occurred during the surgical procedure. The diagnosis was suspected in plain chest X-ray and fluoroscopy. Angiography demonstrated the presence of a false aneurysm of the left atrium which was confirmed at surgery."} {"id": "PMID:1262391", "title": "Filopodia of spreading 3T3 cells. Do they have a substrate-exploring function?", "content": "Freshly plated 3T3 cells send out radial projections or filopodia. We observed cells which happended to settle on glass near the borderline of a gold-plated area. When some of the filopodia contacted the gold-plated area and others the glass substratum and remained attached for a few minutes, lamellipodia then extended preferentially toward the gold-plated area. 1-2 h later, most of the cells were found in the gold-plated area. When the filopodia of a spreading 3T3 cell contacted another already spread 3T3 cell and also the glass substratum, the first lamellipodia extended preferentially towards the glass. These observations suggest a directionally differentiated extension of lamellipodia after the filopodia of a spreading 3T3 cell have contacted different substrates in their environment. Before filopodia contact a substrate, they perform a rapid \"scanning\" motion. Therefore, we suggest that the filopodia of a spreading 3T3 cell serve as organs which explore the nonfluid environment and react to a certain quality of the substrate that is presently unknown. Subsequently, they mediate the extension of lamellipodia into the direction in which this quality is found. The described phenomena are reversibly inhibited by Cytochalasin B at concentrations above 5 mug/ml although filopodia are produced.", "contents": "Filopodia of spreading 3T3 cells. Do they have a substrate-exploring function? Freshly plated 3T3 cells send out radial projections or filopodia. We observed cells which happended to settle on glass near the borderline of a gold-plated area. When some of the filopodia contacted the gold-plated area and others the glass substratum and remained attached for a few minutes, lamellipodia then extended preferentially toward the gold-plated area. 1-2 h later, most of the cells were found in the gold-plated area. When the filopodia of a spreading 3T3 cell contacted another already spread 3T3 cell and also the glass substratum, the first lamellipodia extended preferentially towards the glass. These observations suggest a directionally differentiated extension of lamellipodia after the filopodia of a spreading 3T3 cell have contacted different substrates in their environment. Before filopodia contact a substrate, they perform a rapid \"scanning\" motion. Therefore, we suggest that the filopodia of a spreading 3T3 cell serve as organs which explore the nonfluid environment and react to a certain quality of the substrate that is presently unknown. Subsequently, they mediate the extension of lamellipodia into the direction in which this quality is found. The described phenomena are reversibly inhibited by Cytochalasin B at concentrations above 5 mug/ml although filopodia are produced."} {"id": "PMID:1262388", "title": "Activity of sympathetic nerves in heart during cardiopulmonary bypass in patients.", "content": "The sympathetic nerve activity in heart during cardiopulmonary bypass was studied in 20 patients. The rate of release of dopamine-beta-hydroxylase from cardiac nerves was used as an indicator. It was found that the thoracotomy alone does not represent such a stimulus which would lead unambiguously to sympathetic overactivity in heart. Cardiopulmonary bypass represents, on the other hand, an intensive sympathomimetic stimulus, as it was demonstrated by significnat increase of coronary A-V difference negativity of dopamine-beta-hydroxylase as early in 15th minute of its duration. The washout of enzyme to the end of 30 min. duration of bypass still increased. After finishing of bypass the coronary A-V diff. of dopamine-beta-hydroxylase again decreased.", "contents": "Activity of sympathetic nerves in heart during cardiopulmonary bypass in patients. The sympathetic nerve activity in heart during cardiopulmonary bypass was studied in 20 patients. The rate of release of dopamine-beta-hydroxylase from cardiac nerves was used as an indicator. It was found that the thoracotomy alone does not represent such a stimulus which would lead unambiguously to sympathetic overactivity in heart. Cardiopulmonary bypass represents, on the other hand, an intensive sympathomimetic stimulus, as it was demonstrated by significnat increase of coronary A-V difference negativity of dopamine-beta-hydroxylase as early in 15th minute of its duration. The washout of enzyme to the end of 30 min. duration of bypass still increased. After finishing of bypass the coronary A-V diff. of dopamine-beta-hydroxylase again decreased."} {"id": "PMID:1262392", "title": "Heterogeneity of the alpha subunit of tubulin and the variability of tubulin within a single organism.", "content": "When tubulins obtained from particular microtubules of the sea urchin (ciliary doublet A tubules, flagellar doublet microtubules, and mitotic microtubules) are analyzed by electrophoresis in a polyacrylamide gel system containing sodium dodecyl sulfate and urea, heterogeneity of the alpha subunit, and differences between the tubulins are revealed. The alpha subunit of tubulin from mitotic apparatus and from A microtubules of ciliary doublets is resolved into two bands, while the alpha subunit of flagellar doublet tubulin gives a single band. The mitotic and ciliary tubulins differ in the mobilities of their two alpha species, or in the relative amounts present, or both. The existence of differences between the tubulins has been confirmed by a preliminary analysis of their cyanogen bromide peptides.", "contents": "Heterogeneity of the alpha subunit of tubulin and the variability of tubulin within a single organism. When tubulins obtained from particular microtubules of the sea urchin (ciliary doublet A tubules, flagellar doublet microtubules, and mitotic microtubules) are analyzed by electrophoresis in a polyacrylamide gel system containing sodium dodecyl sulfate and urea, heterogeneity of the alpha subunit, and differences between the tubulins are revealed. The alpha subunit of tubulin from mitotic apparatus and from A microtubules of ciliary doublets is resolved into two bands, while the alpha subunit of flagellar doublet tubulin gives a single band. The mitotic and ciliary tubulins differ in the mobilities of their two alpha species, or in the relative amounts present, or both. The existence of differences between the tubulins has been confirmed by a preliminary analysis of their cyanogen bromide peptides."} {"id": "PMID:1262393", "title": "Incorporation of polypeptides into thylakoid membranes of Chlamydomonas reinhardtii. Cyclic variations.", "content": "A purified fraction of unstacked thylakoid membranes (TMF1u) has been obtained from homogenates of Chlamydomonas reinhardtii (wild type 137+) by using repeated centrifugates in sucrose density gradients and low salt treatment. The contaminants of the fraction are reduced to a few mitochondria (approximately 3% of the total mitochondrial population), a few osmiophilic granules, and fragments of chloroplast envelopes. By SDS-polyacrylamide gel electrophoresis the polypeptide components of TMF1u were resolved into at least 30 bands. To determine the relative rates of assembly of newly synthesized polypeptides into thylakoid membranes, synchronized algal cells were doubly labeled in vivo with L-[14C] and L-[3H]arginine--used for long- and short-term labeling, respectively. TMF1u's were isolated from the labeled cells at selected time points during the cycle and the distribution of radioactivity was assayed in the gel electrophoretograms of their solubilized polypeptides. Incorporation of newly synthesized polypeptides into the bands of the gels was found to occur continuously but differentially throughout the cycle. Maximal rates of incorporation for the majority of the polypeptides were detected shortly after cell division (6D-7D; equivalent to early G1 phase). The rates of radioactive labeling decreased gradually to a low level at the end of the dark period and then rose slightly at the beginning of the next light period. The findings suggest that, in addition to the light/dark control postulated in the past, assembly of newly synthesized proteins into thylakoid membranes is activated by signals at work in the early G1 phase.", "contents": "Incorporation of polypeptides into thylakoid membranes of Chlamydomonas reinhardtii. Cyclic variations. A purified fraction of unstacked thylakoid membranes (TMF1u) has been obtained from homogenates of Chlamydomonas reinhardtii (wild type 137+) by using repeated centrifugates in sucrose density gradients and low salt treatment. The contaminants of the fraction are reduced to a few mitochondria (approximately 3% of the total mitochondrial population), a few osmiophilic granules, and fragments of chloroplast envelopes. By SDS-polyacrylamide gel electrophoresis the polypeptide components of TMF1u were resolved into at least 30 bands. To determine the relative rates of assembly of newly synthesized polypeptides into thylakoid membranes, synchronized algal cells were doubly labeled in vivo with L-[14C] and L-[3H]arginine--used for long- and short-term labeling, respectively. TMF1u's were isolated from the labeled cells at selected time points during the cycle and the distribution of radioactivity was assayed in the gel electrophoretograms of their solubilized polypeptides. Incorporation of newly synthesized polypeptides into the bands of the gels was found to occur continuously but differentially throughout the cycle. Maximal rates of incorporation for the majority of the polypeptides were detected shortly after cell division (6D-7D; equivalent to early G1 phase). The rates of radioactive labeling decreased gradually to a low level at the end of the dark period and then rose slightly at the beginning of the next light period. The findings suggest that, in addition to the light/dark control postulated in the past, assembly of newly synthesized proteins into thylakoid membranes is activated by signals at work in the early G1 phase."} {"id": "PMID:1262394", "title": "Protein incorporation by isolated amphibian oocytes. V. Specificity for vitellogenin incorporation.", "content": "Macromolecules of vitellogenin were sequestered by Xenopus laevis oocytes 20-50 times (on a molar basis) more rapidly than other proteins tested. Selectivity for vitellogenin did not appear to involve molecular size or charge. The Km for vitellogenin incorporation was at least several orders of magnitude less than that for bovine serum albumin (BSA). At concentrations less than 10 mg-ml-1, BSA did not measurably compete with vitellogenin; a slight, apparent competition observed above a BSA concentration of 10 mg-ml-1 was probably spurious. Above a concentration of 2 mg-ml-1, vitellogenin promoted BSA incorporation by about 40%. These results are consistent with the notion that vitellogenin binds to specific receptor sites on the oocyte membrane and is subsequently internalized by micropinocytosis. Other proteins, such as BSA, which do not compete with vitellogenin are most likely to be incorporated by adventitious engulfment during micropinocytosis.", "contents": "Protein incorporation by isolated amphibian oocytes. V. Specificity for vitellogenin incorporation. Macromolecules of vitellogenin were sequestered by Xenopus laevis oocytes 20-50 times (on a molar basis) more rapidly than other proteins tested. Selectivity for vitellogenin did not appear to involve molecular size or charge. The Km for vitellogenin incorporation was at least several orders of magnitude less than that for bovine serum albumin (BSA). At concentrations less than 10 mg-ml-1, BSA did not measurably compete with vitellogenin; a slight, apparent competition observed above a BSA concentration of 10 mg-ml-1 was probably spurious. Above a concentration of 2 mg-ml-1, vitellogenin promoted BSA incorporation by about 40%. These results are consistent with the notion that vitellogenin binds to specific receptor sites on the oocyte membrane and is subsequently internalized by micropinocytosis. Other proteins, such as BSA, which do not compete with vitellogenin are most likely to be incorporated by adventitious engulfment during micropinocytosis."} {"id": "PMID:1262395", "title": "Characterization of cytoplasmic and nuclear genomes in the colorless alga Polytoma. II. General characterization of organelle nucleic acids.", "content": "Polytoma obtusum has a main band DNA (alpha) with a buoyant density in CsC1 of rho = 1.711 g/ml and a light DNA satellite (beta) with rho = 1.682 g/ml. beta-DNA was substantially enriched in a fraction containing small leucoplast fragments and some mitochondria, which was obtained in a pellet sedimenting between 3,000 g and 5,000 g. A crude mitochondrial pellet was also obtained by sedimenting at 12,000 g to recover particulates remaining in the supernate after 10 min at 5,000 g. This fraction contained a third DNA component (gamma) with rho = 1.714 g/ml. We have concluded that the leucoplasts of P. obtusum contain the beta-DNA (1.6882) and the mitochondria possess the gamma-component (1.714). Two distinct classess of ribosomes were isolated and separated by sucrose density gradients, a major 79S species and a minor species at 75S. The major species possessed the 25S and 18S ribosomal RNA (rRNA), characteristic of cytoplasmic ribosomes, and these particles co-sedimented in sucrose gradients with the 79S cytoplasmic ribosomes of Chlamydomonas reinhardtii. The minor species was present in about 2% of the total ribosomal population but showed an eight-to-ninefold enrichment in the leucoplast pellet, suggesting that it was of organelle origin. These 73S particles had RNA components migrating very closely with the 18S and 25S species of the 79S ribosomes, but the base composition of the rRNA from these two classes of ribosomes was significantly different; the rRNA from the 79S ribosomes had a G+C mole ratio of 50.0%, while the rRNA from the 73S class had a ratio of 47.5%. By comparison, chloroplast ribosomes of C. reinhardtii were found to sediment at 70S and contain rRNA molecules of 23S and 16S, with a G + C content of 51.0%. These findings support the concept that the Polytoma leucoplast possesses characteristic genetic and protein-forming systems.", "contents": "Characterization of cytoplasmic and nuclear genomes in the colorless alga Polytoma. II. General characterization of organelle nucleic acids. Polytoma obtusum has a main band DNA (alpha) with a buoyant density in CsC1 of rho = 1.711 g/ml and a light DNA satellite (beta) with rho = 1.682 g/ml. beta-DNA was substantially enriched in a fraction containing small leucoplast fragments and some mitochondria, which was obtained in a pellet sedimenting between 3,000 g and 5,000 g. A crude mitochondrial pellet was also obtained by sedimenting at 12,000 g to recover particulates remaining in the supernate after 10 min at 5,000 g. This fraction contained a third DNA component (gamma) with rho = 1.714 g/ml. We have concluded that the leucoplasts of P. obtusum contain the beta-DNA (1.6882) and the mitochondria possess the gamma-component (1.714). Two distinct classess of ribosomes were isolated and separated by sucrose density gradients, a major 79S species and a minor species at 75S. The major species possessed the 25S and 18S ribosomal RNA (rRNA), characteristic of cytoplasmic ribosomes, and these particles co-sedimented in sucrose gradients with the 79S cytoplasmic ribosomes of Chlamydomonas reinhardtii. The minor species was present in about 2% of the total ribosomal population but showed an eight-to-ninefold enrichment in the leucoplast pellet, suggesting that it was of organelle origin. These 73S particles had RNA components migrating very closely with the 18S and 25S species of the 79S ribosomes, but the base composition of the rRNA from these two classes of ribosomes was significantly different; the rRNA from the 79S ribosomes had a G+C mole ratio of 50.0%, while the rRNA from the 73S class had a ratio of 47.5%. By comparison, chloroplast ribosomes of C. reinhardtii were found to sediment at 70S and contain rRNA molecules of 23S and 16S, with a G + C content of 51.0%. These findings support the concept that the Polytoma leucoplast possesses characteristic genetic and protein-forming systems."} {"id": "PMID:1262396", "title": "Characterization of cytoplasmic and nuclear genomes in the colorless alga Polytoma. III. Ribosomal RNA cistrons of the nucleus and leucoplast.", "content": "The colorless alga Polytoma obtusum has been found to possess leucoplasts, and two kinds of ribosomes with sedimentation values of 73S and 79S. The ribosomal RNA (rRNA) of the 73S but not the 79S ribosomes was shown to hybridize with the leucoplast DNA (rho - 1.682 g/ml). Nuclear DNA of Polytoma (rho = 1.711) showed specific hybridization with rRNA from the 79S ribosomes. Saturation hybridization indicated that only one copy of the rRNA cistrons was present per leucoplast genome, with an average buoyant density of rho = 1.700. On the other hand, about 750 copies of the cytoplasmic rRNA cistrons were present per nuclear genome with a density of rho = 1.709. Heterologous hybridization studies with Chlamydomonas reinhardtii rRNAs showed an estimated 80% homology between the two cytoplasmic rRNAs, but only a 50% homology between chloroplast and leucoplast rRNAs of the two species. We conclude that the leucoplasts of Polytoma derive from chloroplasts of a Chlamydomonas-like ancestor, but that the leucoplast rRNA cistrons have diverged in evolution more extensively than the cistrons for cytoplasmic rRNA.", "contents": "Characterization of cytoplasmic and nuclear genomes in the colorless alga Polytoma. III. Ribosomal RNA cistrons of the nucleus and leucoplast. The colorless alga Polytoma obtusum has been found to possess leucoplasts, and two kinds of ribosomes with sedimentation values of 73S and 79S. The ribosomal RNA (rRNA) of the 73S but not the 79S ribosomes was shown to hybridize with the leucoplast DNA (rho - 1.682 g/ml). Nuclear DNA of Polytoma (rho = 1.711) showed specific hybridization with rRNA from the 79S ribosomes. Saturation hybridization indicated that only one copy of the rRNA cistrons was present per leucoplast genome, with an average buoyant density of rho = 1.700. On the other hand, about 750 copies of the cytoplasmic rRNA cistrons were present per nuclear genome with a density of rho = 1.709. Heterologous hybridization studies with Chlamydomonas reinhardtii rRNAs showed an estimated 80% homology between the two cytoplasmic rRNAs, but only a 50% homology between chloroplast and leucoplast rRNAs of the two species. We conclude that the leucoplasts of Polytoma derive from chloroplasts of a Chlamydomonas-like ancestor, but that the leucoplast rRNA cistrons have diverged in evolution more extensively than the cistrons for cytoplasmic rRNA."} {"id": "PMID:1262397", "title": "Asymmetry of spermiation and sperm surface charge patterns over the giant acrosome in the musk shrew Suncus murinus.", "content": "Spermatozoa of the shrew Suncus murinus, a mammal with abdominal testes, exhibit four unusual features: a giant acrosome; a dorsoventral asymmetry of their spermiation; a dorsoventral asymmetry of their head surface character; and also apparent surface maturity as they enter the epididymis. A Sertoli cell-periacrosomal cisternal complex envelops the giant acrosome during spermatid maturation. Spermiation is heraled by asymmetrical disorganization of the subplasmalemmal components of this complex and is completed by retraction of the Sertoli cell from the ventral and then the dorsal face of the spermatid head. This sequence or release is correlated with an asynchronous acquisition of negative surface charges on the spermatid head-demonstrable on glutaraldehyde-stabilized cells by the binding at pH 1.8 of positively charged colloidal particles of ferric oxide. Mature epididymal spermatozoa exhibit an asymmetry in the patterns of distribution of bound colloid over the dorsal vs. ventral surfaces of the sperm head, as well as regional differences between the tail midpiece and principal piece. Surface distributions of anionic residues and lectin (Con A)-binding sites characteristic of mature Suncus spermatozoa are demonstrable within the testis, unlike the situation in most nannals where distinct modifications of the sperm surface occur during epididymal passage.", "contents": "Asymmetry of spermiation and sperm surface charge patterns over the giant acrosome in the musk shrew Suncus murinus. Spermatozoa of the shrew Suncus murinus, a mammal with abdominal testes, exhibit four unusual features: a giant acrosome; a dorsoventral asymmetry of their spermiation; a dorsoventral asymmetry of their head surface character; and also apparent surface maturity as they enter the epididymis. A Sertoli cell-periacrosomal cisternal complex envelops the giant acrosome during spermatid maturation. Spermiation is heraled by asymmetrical disorganization of the subplasmalemmal components of this complex and is completed by retraction of the Sertoli cell from the ventral and then the dorsal face of the spermatid head. This sequence or release is correlated with an asynchronous acquisition of negative surface charges on the spermatid head-demonstrable on glutaraldehyde-stabilized cells by the binding at pH 1.8 of positively charged colloidal particles of ferric oxide. Mature epididymal spermatozoa exhibit an asymmetry in the patterns of distribution of bound colloid over the dorsal vs. ventral surfaces of the sperm head, as well as regional differences between the tail midpiece and principal piece. Surface distributions of anionic residues and lectin (Con A)-binding sites characteristic of mature Suncus spermatozoa are demonstrable within the testis, unlike the situation in most nannals where distinct modifications of the sperm surface occur during epididymal passage."} {"id": "PMID:1262398", "title": "Divalent cation affinity sites in Paramecium aurelia.", "content": "Sites with high calcium affinity in Paramecium aurelia were identified by high calcium (5 mM) fixation and electron microscope methods. Electron-opaque deposits were observed on the cytoplasmic side of surface membranes, particularly at the basal regions of cilia and trichocyst-pellicle fusion sites. Deposits were also observed on some smooth cytomembranes, within the axoneme of cilia, and on basal bodies. The divalent cations, Mg2+, Mn2+, Sr2+, Ni2+, Ba2+, and Zn2+, could be substituted for Ca2+ in the procedure. Deposits were larger with 5 mM Sr2+. Ba2+, and Mn2+ at ciliary transverse plates and the terminal plate of basal bodies. Microprobe analysis showed that Ca and C1 were concentrated within deposits. In some analyses, S and P were detected in deposits. Also, microprobe analysis of 5 mM Mn2+-fixed P. aurelia showed that those deposits were enriched in Mn and C1 and sometimes enriched in P. Deposits were seen only when the ciliates were actively swimming at the time of fixation. Locomotory mutants having defective membrane Ca-gating mechanisms and ciliates fixed while exhibiting ciliary reversal showed no obvious differences in deposition pattern and intensity. Possible correlations between electron-opaque deposits and the locations of intramembranous particles seen by freeze-fracture studied, as well as sites where fibrillar material associate with membranes are considered. The possibility that the action sites of calcium and other divalent cations were identified is discussed.", "contents": "Divalent cation affinity sites in Paramecium aurelia. Sites with high calcium affinity in Paramecium aurelia were identified by high calcium (5 mM) fixation and electron microscope methods. Electron-opaque deposits were observed on the cytoplasmic side of surface membranes, particularly at the basal regions of cilia and trichocyst-pellicle fusion sites. Deposits were also observed on some smooth cytomembranes, within the axoneme of cilia, and on basal bodies. The divalent cations, Mg2+, Mn2+, Sr2+, Ni2+, Ba2+, and Zn2+, could be substituted for Ca2+ in the procedure. Deposits were larger with 5 mM Sr2+. Ba2+, and Mn2+ at ciliary transverse plates and the terminal plate of basal bodies. Microprobe analysis showed that Ca and C1 were concentrated within deposits. In some analyses, S and P were detected in deposits. Also, microprobe analysis of 5 mM Mn2+-fixed P. aurelia showed that those deposits were enriched in Mn and C1 and sometimes enriched in P. Deposits were seen only when the ciliates were actively swimming at the time of fixation. Locomotory mutants having defective membrane Ca-gating mechanisms and ciliates fixed while exhibiting ciliary reversal showed no obvious differences in deposition pattern and intensity. Possible correlations between electron-opaque deposits and the locations of intramembranous particles seen by freeze-fracture studied, as well as sites where fibrillar material associate with membranes are considered. The possibility that the action sites of calcium and other divalent cations were identified is discussed."} {"id": "PMID:1262399", "title": "Pressure-induced depolymerization of spindle microtubules. III. Differential stability in HeLa cells.", "content": "Evidence from light microscopy (principally polarization microscopy) has demonstrated that hydrostatic pressure can reversibly inhibit mitosis by rapidly depolymerizing the spindle fiber microtubules. We have confirmed this finding in ultrastructural studies of mitotic HeLa cells incubated at 37 degrees C and pressurized at 680 atm (10,000 psi). Althouth there are many spindle microtubules in the cells at atmospheric pressure, electron micographs of cells pressurized for 10 min (and fixed while under pressure in a Landau-Thibodeau chamber) show few microtubules. Pressure has a differential effect on the various types of spindle microtubules. Astral and interpolar MTs appear to be completely depolymerized in pressurized cells, but occasional groups of kinetochore fiber microtubules are seen. Surprisingly, the length and density of microtubules of the stem bodies and midbody of telophase cells appear unchanged by pressurization. In cells fixed 10 min after pressure was released, microtubules were again abundant, the density often appearing to be higher than in control cells. Reorganization seems incomplete, however, since many of the microtubules are randomly oriented. Unexpectedly, kinetochores appeared diffuse and were difficult to identify in sections of pressurized cells. Even after 10 min of recovery at atmospheric pressure, their structure was less distinct than in unpressurized cells.", "contents": "Pressure-induced depolymerization of spindle microtubules. III. Differential stability in HeLa cells. Evidence from light microscopy (principally polarization microscopy) has demonstrated that hydrostatic pressure can reversibly inhibit mitosis by rapidly depolymerizing the spindle fiber microtubules. We have confirmed this finding in ultrastructural studies of mitotic HeLa cells incubated at 37 degrees C and pressurized at 680 atm (10,000 psi). Althouth there are many spindle microtubules in the cells at atmospheric pressure, electron micographs of cells pressurized for 10 min (and fixed while under pressure in a Landau-Thibodeau chamber) show few microtubules. Pressure has a differential effect on the various types of spindle microtubules. Astral and interpolar MTs appear to be completely depolymerized in pressurized cells, but occasional groups of kinetochore fiber microtubules are seen. Surprisingly, the length and density of microtubules of the stem bodies and midbody of telophase cells appear unchanged by pressurization. In cells fixed 10 min after pressure was released, microtubules were again abundant, the density often appearing to be higher than in control cells. Reorganization seems incomplete, however, since many of the microtubules are randomly oriented. Unexpectedly, kinetochores appeared diffuse and were difficult to identify in sections of pressurized cells. Even after 10 min of recovery at atmospheric pressure, their structure was less distinct than in unpressurized cells."} {"id": "PMID:1262400", "title": "Regulation of transcription of genes of ribosomal rna during amphibian oogenesis. A biochemical and morphological study.", "content": "Natural changes in the transcription of rRNA genes were studied in nucleoli from three oogenic stages of the newt Triturus alpestris with electron microscope, auto-radiographic, and biochemical techniques. From determinations of the uridine triphosphate pool sizes and [3H]uridine uptake, phosphorylation, and incorporation into 28S and 18S rRNAs in vivo it was estimated that the rate of rRNA synthesis was about 0.01% in previtellogenic oocytes and 13% in mature oocytes when compared to midvitellogenesis. Spread preparations of nucleoli showed significant morphological changes in the transcriptional complexes. The total number of lateral fibrils, i.e., ribonucleoproteins containing the nascent rRNA precursor, were drastically decreased in stages of reduced synthetic activity. This indicates that rRNA synthesis is regulated primarily at the level of transcription. The resulting patterns of fibril coverage of the nucleolar chromatin axes revealed a marked heterogeneity. On the same nucleolar axis occurred matrix units that were completely devoid of lateral fibrils, matrix units that were almost fully covered with lateral fibrils, and various forms of matrix units with a range of lateral fibril densities intermediate between the two extremes. Granular particles that were tentatively identified as RNA polymerase molecules were not restricted to the transciptional complexes. They were observed, although less regularly and separated by greater distances, in untranscribed spacer regions as well as in untranscribed gene intercepts. The results show that the pattern of transcriptional control of rRNA genes differs widely in different genes, even in the same genetic unit.", "contents": "Regulation of transcription of genes of ribosomal rna during amphibian oogenesis. A biochemical and morphological study. Natural changes in the transcription of rRNA genes were studied in nucleoli from three oogenic stages of the newt Triturus alpestris with electron microscope, auto-radiographic, and biochemical techniques. From determinations of the uridine triphosphate pool sizes and [3H]uridine uptake, phosphorylation, and incorporation into 28S and 18S rRNAs in vivo it was estimated that the rate of rRNA synthesis was about 0.01% in previtellogenic oocytes and 13% in mature oocytes when compared to midvitellogenesis. Spread preparations of nucleoli showed significant morphological changes in the transcriptional complexes. The total number of lateral fibrils, i.e., ribonucleoproteins containing the nascent rRNA precursor, were drastically decreased in stages of reduced synthetic activity. This indicates that rRNA synthesis is regulated primarily at the level of transcription. The resulting patterns of fibril coverage of the nucleolar chromatin axes revealed a marked heterogeneity. On the same nucleolar axis occurred matrix units that were completely devoid of lateral fibrils, matrix units that were almost fully covered with lateral fibrils, and various forms of matrix units with a range of lateral fibril densities intermediate between the two extremes. Granular particles that were tentatively identified as RNA polymerase molecules were not restricted to the transciptional complexes. They were observed, although less regularly and separated by greater distances, in untranscribed spacer regions as well as in untranscribed gene intercepts. The results show that the pattern of transcriptional control of rRNA genes differs widely in different genes, even in the same genetic unit."} {"id": "PMID:1262401", "title": "Demonstration of the fuzzy surface coat of rat intestinal microvilli by freeze-etching.", "content": "In freeze-etch replicas of epithelial cells of rat rectum, the fuzzy surface coat is composed of discrete filaments which are aligned in parallel with each other and with the long axes of the microvilli.", "contents": "Demonstration of the fuzzy surface coat of rat intestinal microvilli by freeze-etching. In freeze-etch replicas of epithelial cells of rat rectum, the fuzzy surface coat is composed of discrete filaments which are aligned in parallel with each other and with the long axes of the microvilli."} {"id": "PMID:1262402", "title": "Reflexive gap junctions. Gap junctions between processing arising from the same ovarian decidual cell.", "content": "Ajacent processes on ovarian decidual cells were shown by electron microscopy to form gap junctions with one another. Micrographs of tissues preserved with lanthanum included in the fixative confirm the hexagonal array and 2-4 nm gap which characterize gap junctions. It is suggested that these gap junctions may play a role in the process of merocrine secretion from the peduncular processes of ovarian decidual cells. The term reflexive gap junction is introduced to describe gap junctions between adjacent processes from the same cell.", "contents": "Reflexive gap junctions. Gap junctions between processing arising from the same ovarian decidual cell. Ajacent processes on ovarian decidual cells were shown by electron microscopy to form gap junctions with one another. Micrographs of tissues preserved with lanthanum included in the fixative confirm the hexagonal array and 2-4 nm gap which characterize gap junctions. It is suggested that these gap junctions may play a role in the process of merocrine secretion from the peduncular processes of ovarian decidual cells. The term reflexive gap junction is introduced to describe gap junctions between adjacent processes from the same cell."} {"id": "PMID:1262403", "title": "Effects of prolonged quiescence on neuclei and chromatin of WI-38 fibroblasts.", "content": "DNA synthesis and cell division are markedly reduced in confluent mono-layers of WI-38 diploid fibroblasts, but resume again if the depleted medium is replaced by fresh medium containing 10% fetal calf serum. If the cells are kept quiescent for prolonged periods of time after confluence (1 or 2 weeks), the fraction of cells that can be stimulated to proliferate by fresh serum decreases and the length of the prereplicative phase increases. The template activity of isolated nuclei decreases with increasing time of quiescence, and parallel changes occur in chromatin as evidenced by circular dichroism spectra and capacity to bind the intercalating dye, ethidium bromide. When WI-38 cells are stimulated to proliferate after prolonged quiescence, the increase in template activity of nuclei is delayed by several hours in comparison to cells stimulated after short periods of quiescence. Two distinct steps, both requiring serum, can be identified in the prereplicative phase of cells stimulated to proliferative after prolonged quiescence. We interpret the results as indicating that, during prolonged quiescence, WI-38 fibroblasts go into a deeper GO state from which they can be rescued only after prolonged stimulation. In this respect, prolonged quiescence may bear some resemblance to the process of aging.", "contents": "Effects of prolonged quiescence on neuclei and chromatin of WI-38 fibroblasts. DNA synthesis and cell division are markedly reduced in confluent mono-layers of WI-38 diploid fibroblasts, but resume again if the depleted medium is replaced by fresh medium containing 10% fetal calf serum. If the cells are kept quiescent for prolonged periods of time after confluence (1 or 2 weeks), the fraction of cells that can be stimulated to proliferate by fresh serum decreases and the length of the prereplicative phase increases. The template activity of isolated nuclei decreases with increasing time of quiescence, and parallel changes occur in chromatin as evidenced by circular dichroism spectra and capacity to bind the intercalating dye, ethidium bromide. When WI-38 cells are stimulated to proliferate after prolonged quiescence, the increase in template activity of nuclei is delayed by several hours in comparison to cells stimulated after short periods of quiescence. Two distinct steps, both requiring serum, can be identified in the prereplicative phase of cells stimulated to proliferative after prolonged quiescence. We interpret the results as indicating that, during prolonged quiescence, WI-38 fibroblasts go into a deeper GO state from which they can be rescued only after prolonged stimulation. In this respect, prolonged quiescence may bear some resemblance to the process of aging."} {"id": "PMID:1262404", "title": "Differences in the incorporation of thymidine into DNA of normal and cystic fibrosis fibroblasts in vitro.", "content": "Although similar fractions of cells were in the S phase of the cell cycle, normal human skin fibroblasts were shown to incorporate more than twice the 3HTdR into their DNA in vitro than did cells obtained from individuals with cystic fibrosis (CF). Obligate heterozygotes incorporated an intermediate amount of the DNA precursor. Studied were initiated to determine the basis of the differential incorporation of 3HTdR among the genotypes. An analog of thymidine, BUdR, produced varied effects on the growth kinetics of the three genotypes. The growth of cells in BUdR resulted in a 50% increase in the population doubling times of all three genotypes, and caused the cell morphology to change from a spindle shape to one in which the cells became broadened and flat, with numerous cytoplasmic projections extending for distances of several cell diameters. The activities of thymidine kinase and the participation of the exogenous and de novo pathways in the synthesis of TMP were found to be approximately the same in all three genotypes. The data suggest that an alteration in the transport of thymidine into the cells may account for the differences in TdR incorporation into DNA, and this may be associated with other changes in cystic fibrosis that are apparently membrane associated.", "contents": "Differences in the incorporation of thymidine into DNA of normal and cystic fibrosis fibroblasts in vitro. Although similar fractions of cells were in the S phase of the cell cycle, normal human skin fibroblasts were shown to incorporate more than twice the 3HTdR into their DNA in vitro than did cells obtained from individuals with cystic fibrosis (CF). Obligate heterozygotes incorporated an intermediate amount of the DNA precursor. Studied were initiated to determine the basis of the differential incorporation of 3HTdR among the genotypes. An analog of thymidine, BUdR, produced varied effects on the growth kinetics of the three genotypes. The growth of cells in BUdR resulted in a 50% increase in the population doubling times of all three genotypes, and caused the cell morphology to change from a spindle shape to one in which the cells became broadened and flat, with numerous cytoplasmic projections extending for distances of several cell diameters. The activities of thymidine kinase and the participation of the exogenous and de novo pathways in the synthesis of TMP were found to be approximately the same in all three genotypes. The data suggest that an alteration in the transport of thymidine into the cells may account for the differences in TdR incorporation into DNA, and this may be associated with other changes in cystic fibrosis that are apparently membrane associated."} {"id": "PMID:1262405", "title": "Human lymphocyte potassium content during the initiation of phytohemagglutinin-induced mitogenesis.", "content": "The K+ content of human lymphocytes has been examined during the initial 24 hours after exposure of cells to phytohemagglutinin (PHA). We have reconfirmed that lymphocyte K+ exchanges rapidly for extracellular counterions during preparative washing if cells are exposed to PHA. By using a technique to measure cation content which does not require removal of cells from their culture medium, we have shown that K+ does not change for 24 hours following PHA treatment. Previous reports have demonstrated that an enhanced uptake of K+ occurs in lymphocytes treated with PHA. This increased uptake may be a compensatory change for an increased exodus, explaining the failure of K+ to change following lectin treatment.", "contents": "Human lymphocyte potassium content during the initiation of phytohemagglutinin-induced mitogenesis. The K+ content of human lymphocytes has been examined during the initial 24 hours after exposure of cells to phytohemagglutinin (PHA). We have reconfirmed that lymphocyte K+ exchanges rapidly for extracellular counterions during preparative washing if cells are exposed to PHA. By using a technique to measure cation content which does not require removal of cells from their culture medium, we have shown that K+ does not change for 24 hours following PHA treatment. Previous reports have demonstrated that an enhanced uptake of K+ occurs in lymphocytes treated with PHA. This increased uptake may be a compensatory change for an increased exodus, explaining the failure of K+ to change following lectin treatment."} {"id": "PMID:1262406", "title": "Formation of thymidine kinase and deoxycytidylate deaminase in synchronized cultures of chinese hamster cells temperature-sensitive for DNA synthesis.", "content": "Cytosol thymidine kinase (TK) and deoxycytidylate (dCMP) deaminase formation was investigated in synchronized cultures of K12 Chinese hamster cells which have a temperature-sensitive lesion affecting the initiation of DNA synthesis. Enzyme formation was found to be cycloheximide-sensitive and also temperature-dependent. Beginning at about six hours after addition of medium with 10% calf serum to serum-depleted K12 cultures, cytosol TK and dCMP deaminase activities increased when the cultures were incubated at 36.5 degrees but not at 40.5 degrees. When cultures were shifted from 36.5 degrees to 40.5 degrees at 4,6, or 8 hours after serum addition, TK activity continued to increase, though not to the level observed at ten hours in cultures maintained at 36.5 degrees. Actinomycin D addition at the time of serum reversal or four hours later blocked the TK increase normally observed at the permissive temperature at ten hours. However, when actinomycin D addition was delayed for six or eight hours after serum addition, the increase in TK measured at ten hours resembled that observed in the temperature shift-up experiments. The results provide evidence that the mutation in K12 Chinese hamster cells most likely blocks the progression through G1 into S and suggest that transcription or post-transcriptional processing required for TK formation is affected.", "contents": "Formation of thymidine kinase and deoxycytidylate deaminase in synchronized cultures of chinese hamster cells temperature-sensitive for DNA synthesis. Cytosol thymidine kinase (TK) and deoxycytidylate (dCMP) deaminase formation was investigated in synchronized cultures of K12 Chinese hamster cells which have a temperature-sensitive lesion affecting the initiation of DNA synthesis. Enzyme formation was found to be cycloheximide-sensitive and also temperature-dependent. Beginning at about six hours after addition of medium with 10% calf serum to serum-depleted K12 cultures, cytosol TK and dCMP deaminase activities increased when the cultures were incubated at 36.5 degrees but not at 40.5 degrees. When cultures were shifted from 36.5 degrees to 40.5 degrees at 4,6, or 8 hours after serum addition, TK activity continued to increase, though not to the level observed at ten hours in cultures maintained at 36.5 degrees. Actinomycin D addition at the time of serum reversal or four hours later blocked the TK increase normally observed at the permissive temperature at ten hours. However, when actinomycin D addition was delayed for six or eight hours after serum addition, the increase in TK measured at ten hours resembled that observed in the temperature shift-up experiments. The results provide evidence that the mutation in K12 Chinese hamster cells most likely blocks the progression through G1 into S and suggest that transcription or post-transcriptional processing required for TK formation is affected."} {"id": "PMID:1262407", "title": "Membrane transport in synchronized Ehrlich ascites tumor cells: uptake of amino acids by the A and L system during the cell cycle.", "content": "Using the double thymidine block technique. Ehrlich ascites tumor cells (ELD) carried in continuous spinner culture have been synchronized. Simultaneous monitoring of 3H-thymidine incorporation, cell number and mitotic index yielded a cell cycle time of approximately 13.5 hours. This is composed of an S period of 3-4 hours. G2 of 6-8 hours and M of 1-2 hours. No appreciable G1 is present. Ehrlich cells synchronized in this manner were used to investigate the characteristics of two neutral amino acid transport systems during progression through the cell cycle. Unidirectional influx via the Na-dependent system A was studied using C14-alpha-aminoisobutyrate (AIB) as substrate. The Na-independent system L was monitored using 3H-leucine and 14C-cycloleucine as substrates. Transport by the A system was minimal in M and early S. It underwent a three-fold increase during late S and early G2. In mid G2 the transport via this system rapidly dropped and remained low again through M and early S. The intracellular/extracellular ratios of AIB indicate that the system is actively transporting AIB thoughout the cell cycle. The minimum ratios of approximately 3 were achieved during early M and the maximum ratios of approximately 9 were achieved in late S, early G2. The uptake of leucine and cycloleucine by the L system was quite different during the cell cycle. Maximal unidirectional influx by this system occurred during early and mid S period. Upon progression into G2 the transport rate dropped and remained reduced throughout M. Intracellular/extracellular ratios of leucine or cycloleucine were near unity at the peak of the transport activity (early S) and dropped to values of 0.5 to 0.6 throughout the remainder of the cycle. This result indicates that inward transport by the L system is, for the most part, non-active in growing cells.", "contents": "Membrane transport in synchronized Ehrlich ascites tumor cells: uptake of amino acids by the A and L system during the cell cycle. Using the double thymidine block technique. Ehrlich ascites tumor cells (ELD) carried in continuous spinner culture have been synchronized. Simultaneous monitoring of 3H-thymidine incorporation, cell number and mitotic index yielded a cell cycle time of approximately 13.5 hours. This is composed of an S period of 3-4 hours. G2 of 6-8 hours and M of 1-2 hours. No appreciable G1 is present. Ehrlich cells synchronized in this manner were used to investigate the characteristics of two neutral amino acid transport systems during progression through the cell cycle. Unidirectional influx via the Na-dependent system A was studied using C14-alpha-aminoisobutyrate (AIB) as substrate. The Na-independent system L was monitored using 3H-leucine and 14C-cycloleucine as substrates. Transport by the A system was minimal in M and early S. It underwent a three-fold increase during late S and early G2. In mid G2 the transport via this system rapidly dropped and remained low again through M and early S. The intracellular/extracellular ratios of AIB indicate that the system is actively transporting AIB thoughout the cell cycle. The minimum ratios of approximately 3 were achieved during early M and the maximum ratios of approximately 9 were achieved in late S, early G2. The uptake of leucine and cycloleucine by the L system was quite different during the cell cycle. Maximal unidirectional influx by this system occurred during early and mid S period. Upon progression into G2 the transport rate dropped and remained reduced throughout M. Intracellular/extracellular ratios of leucine or cycloleucine were near unity at the peak of the transport activity (early S) and dropped to values of 0.5 to 0.6 throughout the remainder of the cycle. This result indicates that inward transport by the L system is, for the most part, non-active in growing cells."} {"id": "PMID:1262408", "title": "Substrate-attached serum and cell proteins in adhesion of mouse fibroblasts.", "content": "The effects of serum and coatings of substrate-attached material (SAM, which remains tightly adherent to the substrate after EGTA-mediated removal of cells) on the kinetics of attachment of DNA-radiolabeled BALB/c 3T3. SV40-transformed 3T3, and concanavalin A-selected revertant cells to glass coverlips were studied. The presence of serum in the medium of attaching cells had a marked effect on (1) the initial time lag before stable attachment of cells, (2) the maximum level of attached cells, (3) the stability of attachment, and (4) pseudopodial spread of the cell over the substrate. These serum effects could be mimicked by measuring attachment in medium without serum and with use of serum-preadsorbed or 3T3 SAM-coated coverslips. Enzymatic treatment of serumpreadsorbed substrates indicated that the factor(s) in serum which affects attachment is very trypsin-sensitive. Serum preadsorption of substrates stimulated attachment of SVT2 cells in medium with serum in a manner very similar to the effects of 3T3 SAM coating, while attachment of 3T3 SAM coating, while attachment of 3T3 or revertant cells was unaffected. Slab gel electrophoretic analysis (PAGE-SDS gels) identified eight major serum proteins by Coomassie blue staining (a) which bind to the substrate in the absence of cells and (b) which persist on the substrate after growth to confluence of 3T3 or SVT2 cells; this suggests that major breakdown or serum-adsorbed components does not occur during growth of normal or transformed cells. Seven radioactive SAM proteins were detected by autoradiography in 3T3 or SVT2 SAM electropherograms -- two of which are high molecular weight components which correspond to the glucosamine-radiolabeled hyaluronate proteoglycans observed previously; the remaining five are newly-identified proteins in SAM (one of these proteins appears to be actin). 3T3 and SVT2 cells have unique proportions of these seven components. The data are consistent with the idea that normal or virus-transformed cells do not attach directly to the culture substrate, but to specific classes of substrate-adsorbed serum proteins via deposition of specific classes of cell surface proteins and polysaccharides.", "contents": "Substrate-attached serum and cell proteins in adhesion of mouse fibroblasts. The effects of serum and coatings of substrate-attached material (SAM, which remains tightly adherent to the substrate after EGTA-mediated removal of cells) on the kinetics of attachment of DNA-radiolabeled BALB/c 3T3. SV40-transformed 3T3, and concanavalin A-selected revertant cells to glass coverlips were studied. The presence of serum in the medium of attaching cells had a marked effect on (1) the initial time lag before stable attachment of cells, (2) the maximum level of attached cells, (3) the stability of attachment, and (4) pseudopodial spread of the cell over the substrate. These serum effects could be mimicked by measuring attachment in medium without serum and with use of serum-preadsorbed or 3T3 SAM-coated coverslips. Enzymatic treatment of serumpreadsorbed substrates indicated that the factor(s) in serum which affects attachment is very trypsin-sensitive. Serum preadsorption of substrates stimulated attachment of SVT2 cells in medium with serum in a manner very similar to the effects of 3T3 SAM coating, while attachment of 3T3 SAM coating, while attachment of 3T3 or revertant cells was unaffected. Slab gel electrophoretic analysis (PAGE-SDS gels) identified eight major serum proteins by Coomassie blue staining (a) which bind to the substrate in the absence of cells and (b) which persist on the substrate after growth to confluence of 3T3 or SVT2 cells; this suggests that major breakdown or serum-adsorbed components does not occur during growth of normal or transformed cells. Seven radioactive SAM proteins were detected by autoradiography in 3T3 or SVT2 SAM electropherograms -- two of which are high molecular weight components which correspond to the glucosamine-radiolabeled hyaluronate proteoglycans observed previously; the remaining five are newly-identified proteins in SAM (one of these proteins appears to be actin). 3T3 and SVT2 cells have unique proportions of these seven components. The data are consistent with the idea that normal or virus-transformed cells do not attach directly to the culture substrate, but to specific classes of substrate-adsorbed serum proteins via deposition of specific classes of cell surface proteins and polysaccharides."} {"id": "PMID:1262409", "title": "Studies on changes in the nuclear helices of Amoeba proteus during the cell cycle.", "content": "The fine structure of the nuclei of synchronously growing cell population of Amoeba proteus was studied at I-h intervals during the interphase. This study showed that the nuclear helices undergo increases in their number at certain stages during interphase. These changes were found to correlate with ultrastructural changes occurring in the nucleoli.", "contents": "Studies on changes in the nuclear helices of Amoeba proteus during the cell cycle. The fine structure of the nuclei of synchronously growing cell population of Amoeba proteus was studied at I-h intervals during the interphase. This study showed that the nuclear helices undergo increases in their number at certain stages during interphase. These changes were found to correlate with ultrastructural changes occurring in the nucleoli."} {"id": "PMID:1262410", "title": "The localization of (3H) thymidine incorporation in the DNA of replicating spinach chloroplasts by electron-microscope autoradiography.", "content": "Electron-microscope autoradiography has been used to obtain information on the localization of DNA labelled with [3H]thymidine in chloroplasts known to be replicating and concomitantly synthesizing and segregating DNA, in cultured leaf disks. The studies were made using both Microdol-X developer and a 'compact' developer which gave a smaller grain size. About 80% of the grains were associated with the granal membranes and with presumptive DNA regions (3-nm fibril material in clear areas). Few grains occurred in association with the chloroplast envelope. We suggest that the DNA of chloroplasts is associated with the grana lamellae and extends into the stroma. Some light-microscope autoradiographs of whole chloroplasts show spiral or helical-like labelling patterns. We interpret these patterns as demonstration of the possibility that DNA occurs along the length of a continuous lamellar membrane system. Chloroplast fractionation experiments provided data consistent with the electron-microscope autoradiographic studies as most of the label was associated with chlorophyll-containing lamellae. We consider an association of chloroplast DNA molecules along the length of a continuous lamellar system would ensure an orderly segregation of DNA to daughter chloroplasts, during the binary fission of spinach chloroplasts by constriction division.", "contents": "The localization of (3H) thymidine incorporation in the DNA of replicating spinach chloroplasts by electron-microscope autoradiography. Electron-microscope autoradiography has been used to obtain information on the localization of DNA labelled with [3H]thymidine in chloroplasts known to be replicating and concomitantly synthesizing and segregating DNA, in cultured leaf disks. The studies were made using both Microdol-X developer and a 'compact' developer which gave a smaller grain size. About 80% of the grains were associated with the granal membranes and with presumptive DNA regions (3-nm fibril material in clear areas). Few grains occurred in association with the chloroplast envelope. We suggest that the DNA of chloroplasts is associated with the grana lamellae and extends into the stroma. Some light-microscope autoradiographs of whole chloroplasts show spiral or helical-like labelling patterns. We interpret these patterns as demonstration of the possibility that DNA occurs along the length of a continuous lamellar membrane system. Chloroplast fractionation experiments provided data consistent with the electron-microscope autoradiographic studies as most of the label was associated with chlorophyll-containing lamellae. We consider an association of chloroplast DNA molecules along the length of a continuous lamellar system would ensure an orderly segregation of DNA to daughter chloroplasts, during the binary fission of spinach chloroplasts by constriction division."} {"id": "PMID:1262411", "title": "Goblet cell membrane differentiations in the midgut of a lepidopteran larva.", "content": "So-called goblet cells are present in the midgut of lepidopteran larvae. They are thought to be involved in the active transport of potassium out of the haemolymph and into the gut lumen. A number of plasma membrane differentiations within the goblet cell cavity has been investigated using conventional staining, lanthanum tracer and freeze-etch techniques. Of particular interest are junction-like inter- and intra-membrane differentiations found on the villus-like cytoplasmic projections present at the apical tip of the goblet cell cavities. These cytoplasmic projections appear to act as a valve; in some cases they seem to close off the top of the goblet cell cavity, so isolating it from the gut lumen, while in other cases they are spread apart leaving a wide channel from the cavity into the lumen. The junction-like structures on these cytoplasmic projections are different in structure from the septate-type junctions which seal the midgut cells together at their apical borders, and the 2 types are present on the same plasma membrane, often within one micron of each other. The need for a different type of junction may possibly be related to the fact that it occurs between 2 areas of the same plasma membrane. The morphology of this unusual junction-like structure is discussed and 2 diagrams are presented to illustrate our interpretation of its structure.", "contents": "Goblet cell membrane differentiations in the midgut of a lepidopteran larva. So-called goblet cells are present in the midgut of lepidopteran larvae. They are thought to be involved in the active transport of potassium out of the haemolymph and into the gut lumen. A number of plasma membrane differentiations within the goblet cell cavity has been investigated using conventional staining, lanthanum tracer and freeze-etch techniques. Of particular interest are junction-like inter- and intra-membrane differentiations found on the villus-like cytoplasmic projections present at the apical tip of the goblet cell cavities. These cytoplasmic projections appear to act as a valve; in some cases they seem to close off the top of the goblet cell cavity, so isolating it from the gut lumen, while in other cases they are spread apart leaving a wide channel from the cavity into the lumen. The junction-like structures on these cytoplasmic projections are different in structure from the septate-type junctions which seal the midgut cells together at their apical borders, and the 2 types are present on the same plasma membrane, often within one micron of each other. The need for a different type of junction may possibly be related to the fact that it occurs between 2 areas of the same plasma membrane. The morphology of this unusual junction-like structure is discussed and 2 diagrams are presented to illustrate our interpretation of its structure."} {"id": "PMID:1262412", "title": "The secretion of collagen by insects: uptake of [3H]proline by collagen-synthesizing cells in Locusta migratoria and Galleria mellonella.", "content": "The uptake of [H3]proline by collagen-secreting cells of the locust, Locusta migratoria, and wax-moth, Galleria mellonella, has been investigated by electron autoradiography. The locust cells are around the ejaculatory duct and they secrete collagen in the young adult male, while the wax-moth cells are those which produce the dorsal mass of connective tissue on the abdominal nerve cord during the late pupal stage. The cells were exposed to [H3]proline either by injection of the [3H]proline into the insect, or as a pulse while the tissue was maintained in a culture medium. The tissues were fixed at differeing experimental times after exposure to the [3H]proline. The resulting electron autoradiographs were subjected to quantitative analysis, and the silver grain distribution was determined as the relative number of grains per unit area over a series of tissue compartments. When the results of this analysis for the matrix, rough endoplasmic reticulum and Golgi complexes of the two tissues were plotted against experimental time, it was seen that the relative number of grains per unit area over the rough endoplasmic reticulum decreases while that over the matrix increases; statistical analysis has shown that these changes are significant. For the Golgi complexes, however, the theoretical variances are much greater, due to the small relative area occupied by this organelle. There is little evidence for anything other than random sampling fluctuations in the relative numbers of grains per unit area, and hence it is unlikely that the time course of the label over the Golgi complexes follows that over the rough endoplasmic reticulum. The conclusions drawn from these experiments are firstly that a large portion of the labelled protein passes straight from the rough endoplasmic reticulum to the matrix, but that a smaller portion of the labelled material might pass from the rough endoplasmic reticulum to the Golgi complexes and thence to the matrix. It is assumed that collagen comprises most of the protein which passes straight from the rough endoplasmic reticulum to the matrix, and while there is no evidence to exclude collagen from the material passing through the Golgi complexes, it is probable that other proteins and glycosaminoglycans are also present in this labelled material. These conclusions about the intracellular pathway for collagen secretion are similar to those derived from recent studies of some vertebrate fibroblasts. There is, however, conflicting opinion about the intracellular pathway of collagen and it is pointed out that there is diversity in collagen-synthesizing cells, which may account for the differences in the intracellular pathways for collagen secretion which have been proposed.", "contents": "The secretion of collagen by insects: uptake of [3H]proline by collagen-synthesizing cells in Locusta migratoria and Galleria mellonella. The uptake of [H3]proline by collagen-secreting cells of the locust, Locusta migratoria, and wax-moth, Galleria mellonella, has been investigated by electron autoradiography. The locust cells are around the ejaculatory duct and they secrete collagen in the young adult male, while the wax-moth cells are those which produce the dorsal mass of connective tissue on the abdominal nerve cord during the late pupal stage. The cells were exposed to [H3]proline either by injection of the [3H]proline into the insect, or as a pulse while the tissue was maintained in a culture medium. The tissues were fixed at differeing experimental times after exposure to the [3H]proline. The resulting electron autoradiographs were subjected to quantitative analysis, and the silver grain distribution was determined as the relative number of grains per unit area over a series of tissue compartments. When the results of this analysis for the matrix, rough endoplasmic reticulum and Golgi complexes of the two tissues were plotted against experimental time, it was seen that the relative number of grains per unit area over the rough endoplasmic reticulum decreases while that over the matrix increases; statistical analysis has shown that these changes are significant. For the Golgi complexes, however, the theoretical variances are much greater, due to the small relative area occupied by this organelle. There is little evidence for anything other than random sampling fluctuations in the relative numbers of grains per unit area, and hence it is unlikely that the time course of the label over the Golgi complexes follows that over the rough endoplasmic reticulum. The conclusions drawn from these experiments are firstly that a large portion of the labelled protein passes straight from the rough endoplasmic reticulum to the matrix, but that a smaller portion of the labelled material might pass from the rough endoplasmic reticulum to the Golgi complexes and thence to the matrix. It is assumed that collagen comprises most of the protein which passes straight from the rough endoplasmic reticulum to the matrix, and while there is no evidence to exclude collagen from the material passing through the Golgi complexes, it is probable that other proteins and glycosaminoglycans are also present in this labelled material. These conclusions about the intracellular pathway for collagen secretion are similar to those derived from recent studies of some vertebrate fibroblasts. There is, however, conflicting opinion about the intracellular pathway of collagen and it is pointed out that there is diversity in collagen-synthesizing cells, which may account for the differences in the intracellular pathways for collagen secretion which have been proposed."} {"id": "PMID:1262413", "title": "Flagellar doublet microtubules: fractionation of minor components and alpha-tubulin from specific regions of the A-tubule.", "content": "Proteins occurring minor amounts with purified sperm flagellar doublet microtubules were identified and studied by SDS-gel electrophoresis. Methods were developed to solubilize selectively these minor components; electron microscopy (EM) of the fractionated products revealed possible locations of these proteins in the tubule. Doublet microtubules were prepared from sea-urchin (Echinus esculentus and Stronglyocentrotus droebachiensis) and scallop (Pecten maximus) sperm by dialysing flagellar axonemes against 2 mM Tris-0-2 mM EDTA-0-5 mM DTT. EM indicates that these doublet tubule preparations retain at least 70% of their radial spokes; cross-sections show a globule or fibre applied to the inside wall of the A-tubule, across from the inner B-tubule junction. On SDS-gels these preparations separate into at least 10 minor bands, accounting for 20-30% of the total protein; the remaining 75 +/- 4% migrates as tubulin. For E. esculentus the molecular weights and relative amounts of these components are: Component Ee 8 (150000 Daltons; 1%), 11 (114000; 2-5%), 15 (89000; 2%), 16 (80000; 2-5%), 17 (74000; 2%), 18 (69000; 2%), 19 (66000; 2%), 21 (48000; 4-5%), 22 (45000; 3%) and 23 (44500; 3%). Treatment of sea-urchin tubules with 0-1-0-5% sarkosyl, 0-1-0-3 M KSCN or 0-3-0-6 M KI results in the selective solubilization of: first, component 8 and some B-subfibre tubulin; second, components 11 and 23 and the remaining B-subfire tubulin; third, most of the A-subfire tubulin and components 17, 18 and 19. Thermal fractionation extracts none of these components, suggesting they are principally associated with the A-tubule. Finally 25-35% of the original protein is resistant to solubilization, and appears in the EM as ribbons of 3 protofilaments with 16-nm axial repeats. The resistant ribbons contain components 15, 16, 21 and 22 (plus component 20 in S. droebachiensis) in addition to 25 +/- 4% of the total tubulin. The data support the existence of two stable moieties in each doublet tubule: (1) a ribbon of 3 protofilaments and (2) either a second ribbon of 3 protofilaments or an equivalent amount of tubulin in some other form. EM images suggest that one ribbon forms the lateral side of the A-tubule (e.g. protofilaments A1,2,3 or A13,1,2 in the model) and that the globule applied to A13 may be a multisubunit complex of remaining minor components. Treatment of scallop tubules with 0-3 M KSCN preferentially extracts alpha-tubulin, yielding ribbons 1-4 protofilaments wide. The significance of this finding is discussed.", "contents": "Flagellar doublet microtubules: fractionation of minor components and alpha-tubulin from specific regions of the A-tubule. Proteins occurring minor amounts with purified sperm flagellar doublet microtubules were identified and studied by SDS-gel electrophoresis. Methods were developed to solubilize selectively these minor components; electron microscopy (EM) of the fractionated products revealed possible locations of these proteins in the tubule. Doublet microtubules were prepared from sea-urchin (Echinus esculentus and Stronglyocentrotus droebachiensis) and scallop (Pecten maximus) sperm by dialysing flagellar axonemes against 2 mM Tris-0-2 mM EDTA-0-5 mM DTT. EM indicates that these doublet tubule preparations retain at least 70% of their radial spokes; cross-sections show a globule or fibre applied to the inside wall of the A-tubule, across from the inner B-tubule junction. On SDS-gels these preparations separate into at least 10 minor bands, accounting for 20-30% of the total protein; the remaining 75 +/- 4% migrates as tubulin. For E. esculentus the molecular weights and relative amounts of these components are: Component Ee 8 (150000 Daltons; 1%), 11 (114000; 2-5%), 15 (89000; 2%), 16 (80000; 2-5%), 17 (74000; 2%), 18 (69000; 2%), 19 (66000; 2%), 21 (48000; 4-5%), 22 (45000; 3%) and 23 (44500; 3%). Treatment of sea-urchin tubules with 0-1-0-5% sarkosyl, 0-1-0-3 M KSCN or 0-3-0-6 M KI results in the selective solubilization of: first, component 8 and some B-subfibre tubulin; second, components 11 and 23 and the remaining B-subfire tubulin; third, most of the A-subfire tubulin and components 17, 18 and 19. Thermal fractionation extracts none of these components, suggesting they are principally associated with the A-tubule. Finally 25-35% of the original protein is resistant to solubilization, and appears in the EM as ribbons of 3 protofilaments with 16-nm axial repeats. The resistant ribbons contain components 15, 16, 21 and 22 (plus component 20 in S. droebachiensis) in addition to 25 +/- 4% of the total tubulin. The data support the existence of two stable moieties in each doublet tubule: (1) a ribbon of 3 protofilaments and (2) either a second ribbon of 3 protofilaments or an equivalent amount of tubulin in some other form. EM images suggest that one ribbon forms the lateral side of the A-tubule (e.g. protofilaments A1,2,3 or A13,1,2 in the model) and that the globule applied to A13 may be a multisubunit complex of remaining minor components. Treatment of scallop tubules with 0-3 M KSCN preferentially extracts alpha-tubulin, yielding ribbons 1-4 protofilaments wide. The significance of this finding is discussed."} {"id": "PMID:1262414", "title": "Platelet dense bodies: a quantitative microprobe analysis.", "content": "The electron microprobe shows that the dense bodies of human platelets have a mean P:Ca peak ratio of 1-2. After treatment with dry chloroform/methanol this falls to 0-89. These ratios vary slightly from patient to patient. The use of calcium and phosphorus standards enables these peak ratios to be converted to atomic ratios. The size of the phosphorus peak remaining after lipid extraction was given absolute terms with reference to the known quantities of adenine nucleotides and inorganic pyrophosphate in dense bodies. From the mean P:Ca atomic ratio of 1-76 the quantity of calcium in dense bodies was 0-6 mg/10(11) platelets or 2-97 mg Ca/g dry weight of platelets. This is within the published range for total platelet calcium. If all the phosphorus extracted by lipid solvents were phospholipid there would be 5-65 mg/10(11) platelets, and it would occupy most of the space inside dense bodies. The dense bodies of pig platelets contain both magnesium and calcium in a varying ratio to each other. These results are discussed in relation to control mechanisms that may influence aggregation.", "contents": "Platelet dense bodies: a quantitative microprobe analysis. The electron microprobe shows that the dense bodies of human platelets have a mean P:Ca peak ratio of 1-2. After treatment with dry chloroform/methanol this falls to 0-89. These ratios vary slightly from patient to patient. The use of calcium and phosphorus standards enables these peak ratios to be converted to atomic ratios. The size of the phosphorus peak remaining after lipid extraction was given absolute terms with reference to the known quantities of adenine nucleotides and inorganic pyrophosphate in dense bodies. From the mean P:Ca atomic ratio of 1-76 the quantity of calcium in dense bodies was 0-6 mg/10(11) platelets or 2-97 mg Ca/g dry weight of platelets. This is within the published range for total platelet calcium. If all the phosphorus extracted by lipid solvents were phospholipid there would be 5-65 mg/10(11) platelets, and it would occupy most of the space inside dense bodies. The dense bodies of pig platelets contain both magnesium and calcium in a varying ratio to each other. These results are discussed in relation to control mechanisms that may influence aggregation."} {"id": "PMID:1262416", "title": "Separation of free and protein-bound ligands in the radioimmunoassay by gel filtration-centrifugation.", "content": "The application of gel filtration-centrifugation to the separation of free and protein-bound ligands in radioimmunoassay is described. The method is simple and rapid. A large number of samples can be handled simultaneously and the bount radioactivity is directly transferred to the scintillation vial. Using a 9 X 36 mm column of Sephadex G-50 (coarse), 400 mul of the reaction mixture can be separated during 2 min centrifugation.", "contents": "Separation of free and protein-bound ligands in the radioimmunoassay by gel filtration-centrifugation. The application of gel filtration-centrifugation to the separation of free and protein-bound ligands in radioimmunoassay is described. The method is simple and rapid. A large number of samples can be handled simultaneously and the bount radioactivity is directly transferred to the scintillation vial. Using a 9 X 36 mm column of Sephadex G-50 (coarse), 400 mul of the reaction mixture can be separated during 2 min centrifugation."} {"id": "PMID:1262417", "title": "High-pressure liquid chromatography of steroidal alkaloids.", "content": "High-pressure liquid chromatography was used to separate the following steroidal alkaloids: tomatidine, solanidine, solasodine, rubijervine, veratramine and jervine. The method was used to prepare crystalline solanidine from a crude mixture of aglycones obtained from Solanum chacoense, and to separate radioactive solanidine from extracts of potato plants fed with [4-C]cholesterol.", "contents": "High-pressure liquid chromatography of steroidal alkaloids. High-pressure liquid chromatography was used to separate the following steroidal alkaloids: tomatidine, solanidine, solasodine, rubijervine, veratramine and jervine. The method was used to prepare crystalline solanidine from a crude mixture of aglycones obtained from Solanum chacoense, and to separate radioactive solanidine from extracts of potato plants fed with [4-C]cholesterol."} {"id": "PMID:1262418", "title": "Chromatography of biopolymers and their fragments on ion-exchange derivatives of the hydrophilic macroporous synthetic gel spheron.", "content": "New ion-exchange materials have been developed from the synthetic glycol methacrylate gel Spheron: carboxymethyl-Spheron (weakly acidic); phosphonyl-Spheron (medium acidic); sulphonyl-Spheron (strongly acidic); diethylaminoethyl-Spheron (Type 1, weakly basic; Type 2, medium to strongly basic). Information is presented on the chromatographic characteristics of these new, macroporous, hydrophilic and rigid ion-exchangers as determined by experiments on the separation of mixtures of proteins, peptides, amino acids, nucleic acids, oligonucleotides, and nucleotides. The possibility is discussed of the use of ion-exchangers of this type in high-performance liquid chromatography of biopolymers.", "contents": "Chromatography of biopolymers and their fragments on ion-exchange derivatives of the hydrophilic macroporous synthetic gel spheron. New ion-exchange materials have been developed from the synthetic glycol methacrylate gel Spheron: carboxymethyl-Spheron (weakly acidic); phosphonyl-Spheron (medium acidic); sulphonyl-Spheron (strongly acidic); diethylaminoethyl-Spheron (Type 1, weakly basic; Type 2, medium to strongly basic). Information is presented on the chromatographic characteristics of these new, macroporous, hydrophilic and rigid ion-exchangers as determined by experiments on the separation of mixtures of proteins, peptides, amino acids, nucleic acids, oligonucleotides, and nucleotides. The possibility is discussed of the use of ion-exchangers of this type in high-performance liquid chromatography of biopolymers."} {"id": "PMID:1262419", "title": "Gas-liquid chromatographic analysis of trimethylsilyl derivatives of pyrimidine and purine bases and nucleosides.", "content": "A systematic study of basic nucleic acid components and their biologically significant derivatives has been carried out. The optimum silylation conditions have been found and the chromatographic behaviour of the trimethylsilyl derivatives formed has been studied. Relations between the gas chromatographic behaviour and the structure of the substances analyzed were investigated on the basis of the retention indices measured on two stationary phases of different polarity. The relative molar responses were determined for the quantitative determination of the substances. The results make possible the determination of biologically active substances in pharmaceuticals.", "contents": "Gas-liquid chromatographic analysis of trimethylsilyl derivatives of pyrimidine and purine bases and nucleosides. A systematic study of basic nucleic acid components and their biologically significant derivatives has been carried out. The optimum silylation conditions have been found and the chromatographic behaviour of the trimethylsilyl derivatives formed has been studied. Relations between the gas chromatographic behaviour and the structure of the substances analyzed were investigated on the basis of the retention indices measured on two stationary phases of different polarity. The relative molar responses were determined for the quantitative determination of the substances. The results make possible the determination of biologically active substances in pharmaceuticals."} {"id": "PMID:1262420", "title": "Isotachophoretic analysis of peptides.", "content": "Operating conditions for the qualitative and quantitative determination of plasma kinins, human angiotensin, reduced and oxidized glutathiones and oligopeptides with the same amino acid residues by capillary-tube isotachophoresis using a potential gradient detector have been established. The potential unit (PU) value is proposed as a qualitative index for capillary-tube isotachophoresis with a potential gradient detector. As it is unaffected by changes in the operating conditions, the PU value permits inter-laboratory comparison of data. The coefficient of variation of this index under the various operating conditions used was less than 1.69%.", "contents": "Isotachophoretic analysis of peptides. Operating conditions for the qualitative and quantitative determination of plasma kinins, human angiotensin, reduced and oxidized glutathiones and oligopeptides with the same amino acid residues by capillary-tube isotachophoresis using a potential gradient detector have been established. The potential unit (PU) value is proposed as a qualitative index for capillary-tube isotachophoresis with a potential gradient detector. As it is unaffected by changes in the operating conditions, the PU value permits inter-laboratory comparison of data. The coefficient of variation of this index under the various operating conditions used was less than 1.69%."} {"id": "PMID:1262421", "title": "Gas chromatographic identification of some organochlorine pesticides and their photoalteration products by means of Kovats' retention indices.", "content": "Kovats' retention indices and temperature coefficients for some chlorinated methanonaphthalene and methanoindene pesticides and their photoproducts were determined on an OV-17 silicone liquid phase at three different temperatures. A detailed procedure for the off-line calculation of the retention indices, (see article) and I values are described. The program, written in BASIC, calculates the indices at three different temperatures and provides a computer-written report.", "contents": "Gas chromatographic identification of some organochlorine pesticides and their photoalteration products by means of Kovats' retention indices. Kovats' retention indices and temperature coefficients for some chlorinated methanonaphthalene and methanoindene pesticides and their photoproducts were determined on an OV-17 silicone liquid phase at three different temperatures. A detailed procedure for the off-line calculation of the retention indices, (see article) and I values are described. The program, written in BASIC, calculates the indices at three different temperatures and provides a computer-written report."} {"id": "PMID:1262422", "title": "Gas chromatographic separation of cis-trans isomers: methyl oleate/methyl elaidate.", "content": "The factors which contribute to the separation of methyl elaidate/methyl oleate are examined. These factors include the nitrile content of the stationary phase, the type and nature of the support surface as well as the amount of stationary phase and the column temperature. Baseline separation of the elaidate/oleate pair is obtained with either 15% SP-2340 or OV-275 on Chromosorb P AW-DMCS.", "contents": "Gas chromatographic separation of cis-trans isomers: methyl oleate/methyl elaidate. The factors which contribute to the separation of methyl elaidate/methyl oleate are examined. These factors include the nitrile content of the stationary phase, the type and nature of the support surface as well as the amount of stationary phase and the column temperature. Baseline separation of the elaidate/oleate pair is obtained with either 15% SP-2340 or OV-275 on Chromosorb P AW-DMCS."} {"id": "PMID:1262429", "title": "Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests.", "content": "Insulin secretion and glucose disappearance rate were measured in 66 subjects with a wide range of fasting plasma glucose levels. The acute insulin response was present in subjects with fasting glucose levels below 115 mg/dl but was absent above this level. The glucose disappearance rate related to the relative acute insulin response in subjects with fasting glucose below 115 mg/dl and to total insulin response when fasting glucose levels were above 115 mg/dl. A calculated glucose disappearance rate of 1.06 per cent per minute was found when the acute isulin response was zero. All subjects with fasting glucose levels greater than 115 mg/dl had glucose disappearance rates greater than 1.06. These studies support 1) epidemiological data indicating 115 mg/dl as an upper limit of normal for fasting plasma glucose levels and 1.0 per cent per minute as a lower limit of normal for the glucose disappearance rate, and 2) evidence for an important role for the acute insulin response in the determination of glucose disappearance rates during intravenous glucose tolerance tests.", "contents": "Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. Insulin secretion and glucose disappearance rate were measured in 66 subjects with a wide range of fasting plasma glucose levels. The acute insulin response was present in subjects with fasting glucose levels below 115 mg/dl but was absent above this level. The glucose disappearance rate related to the relative acute insulin response in subjects with fasting glucose below 115 mg/dl and to total insulin response when fasting glucose levels were above 115 mg/dl. A calculated glucose disappearance rate of 1.06 per cent per minute was found when the acute isulin response was zero. All subjects with fasting glucose levels greater than 115 mg/dl had glucose disappearance rates greater than 1.06. These studies support 1) epidemiological data indicating 115 mg/dl as an upper limit of normal for fasting plasma glucose levels and 1.0 per cent per minute as a lower limit of normal for the glucose disappearance rate, and 2) evidence for an important role for the acute insulin response in the determination of glucose disappearance rates during intravenous glucose tolerance tests."} {"id": "PMID:1262430", "title": "Concurrence of aldosterone, androgen, and cortisol secretion in adrenal venous effluents.", "content": "Adrenal effluent concentrations of aldosterone were measured along with testosterone, androstenedione, and cortisol in 17 women with idiopathic hirsutism. In the basal state, aldosterone secretion (higher concentrations vs peripheral blood) was demonstrated in 14 out of 16 of the women, in contrast to 8 out of 16 who demonstrated cortisol gradients. Nine women received 0.25 mgm beta 1-24 ACTH im and serial adrenal venous blood samples were obtained over the next 30 minutes. Parallel 30-40-fold increments were noted in aldosterone, androstenedione, and cortisol; testosterone increased only 8-fold. These marked changes in adrenal effluents were not observed in simultaneously monitored peripheral blood. Minimal changes in these steroid concentrations were noted in adrenal and peripheral blood in 7 women who received 2,000 IU hCG. One woman received a pressor dose of angiotensin II, resulting in a marked increase in adrenal vein aldosterone and a simultaneous decrease in cortisol. Since adrenal androgen secretion parallels cortisol, quantification of adrenal androgen secretion rates can be achieved by sampling the adrenal effluent and relating the androgen gradient to that of cortisol at any given time. In contrast, aldosterone secretion is often independent of cortisol, and thus cannot be estimated by comparison of adrenal gradients. ACTH administration, however, invariably stimulated aldosterone secretion, enabling us to quantify the \"ACTH-related aldosterone secretion rate\" from a comparison of maximal adrenal gradients of aldosterone vs cortisol. In 6 women, \"ACTH-related aldosterone\" secretion rate averaged 40 mug/day, roughly 20% of the total daily aldosterone secretion rate.", "contents": "Concurrence of aldosterone, androgen, and cortisol secretion in adrenal venous effluents. Adrenal effluent concentrations of aldosterone were measured along with testosterone, androstenedione, and cortisol in 17 women with idiopathic hirsutism. In the basal state, aldosterone secretion (higher concentrations vs peripheral blood) was demonstrated in 14 out of 16 of the women, in contrast to 8 out of 16 who demonstrated cortisol gradients. Nine women received 0.25 mgm beta 1-24 ACTH im and serial adrenal venous blood samples were obtained over the next 30 minutes. Parallel 30-40-fold increments were noted in aldosterone, androstenedione, and cortisol; testosterone increased only 8-fold. These marked changes in adrenal effluents were not observed in simultaneously monitored peripheral blood. Minimal changes in these steroid concentrations were noted in adrenal and peripheral blood in 7 women who received 2,000 IU hCG. One woman received a pressor dose of angiotensin II, resulting in a marked increase in adrenal vein aldosterone and a simultaneous decrease in cortisol. Since adrenal androgen secretion parallels cortisol, quantification of adrenal androgen secretion rates can be achieved by sampling the adrenal effluent and relating the androgen gradient to that of cortisol at any given time. In contrast, aldosterone secretion is often independent of cortisol, and thus cannot be estimated by comparison of adrenal gradients. ACTH administration, however, invariably stimulated aldosterone secretion, enabling us to quantify the \"ACTH-related aldosterone secretion rate\" from a comparison of maximal adrenal gradients of aldosterone vs cortisol. In 6 women, \"ACTH-related aldosterone\" secretion rate averaged 40 mug/day, roughly 20% of the total daily aldosterone secretion rate."} {"id": "PMID:1262431", "title": "Episodic 24-hour cortisol secretory patterns in patients awaiting elective cardiac surgery.", "content": "The 24-hour pattern of plasma cortisol concentration in four patients on the day before major elective surgery was compared with that of five similarly hospitalized control subjects to study the effect of the expectation of surgery on the secretion pattern. Using an indwelling venous catheter, which extended outside the patient's room, to collect blood samples every 20 minutes for 24 hours, it was found that cortisol was secreted episodically in both control subjects and presurgical patients. The nychthermal patterns of plasma cortisol concentration in the two groups were indistinguishable for most of the day despite the occurrence of intermittent events which appeared to cause anxiety in the presurgical patients. However, between 9 PM and 11 PM, while each presurgical patient was being preoperatively prepared (body shaving, wash, and enema), a major pulse of cortisol secretion occurred, raising the plasma cortisol concentration to between 6.9-10.5 standard deviations above that of the control subject mean for that time of day. We conclude that 1) expectation of a major surgical procedure for several weeks does not result in chronic activation of the pituitary-adrenocortical axis, 2) many discrete anxiety-provoking events do not evoke cortisol secretory episodes, 3) most episodes of cortisol secretion are part of an endogenous cyclical pattern with a circadian distribution and are not a direct result of environmental stimuli, and 4) preoperative preparation evokes a major cortisol secretory response in patients awaiting surgery. Whether that release of cortisol is a response to the physical manipulations or the psychological implications of that stimulus is presently unknown.", "contents": "Episodic 24-hour cortisol secretory patterns in patients awaiting elective cardiac surgery. The 24-hour pattern of plasma cortisol concentration in four patients on the day before major elective surgery was compared with that of five similarly hospitalized control subjects to study the effect of the expectation of surgery on the secretion pattern. Using an indwelling venous catheter, which extended outside the patient's room, to collect blood samples every 20 minutes for 24 hours, it was found that cortisol was secreted episodically in both control subjects and presurgical patients. The nychthermal patterns of plasma cortisol concentration in the two groups were indistinguishable for most of the day despite the occurrence of intermittent events which appeared to cause anxiety in the presurgical patients. However, between 9 PM and 11 PM, while each presurgical patient was being preoperatively prepared (body shaving, wash, and enema), a major pulse of cortisol secretion occurred, raising the plasma cortisol concentration to between 6.9-10.5 standard deviations above that of the control subject mean for that time of day. We conclude that 1) expectation of a major surgical procedure for several weeks does not result in chronic activation of the pituitary-adrenocortical axis, 2) many discrete anxiety-provoking events do not evoke cortisol secretory episodes, 3) most episodes of cortisol secretion are part of an endogenous cyclical pattern with a circadian distribution and are not a direct result of environmental stimuli, and 4) preoperative preparation evokes a major cortisol secretory response in patients awaiting surgery. Whether that release of cortisol is a response to the physical manipulations or the psychological implications of that stimulus is presently unknown."} {"id": "PMID:1262432", "title": "Thyroid iodine organification defects: a case with lack of thyroglobulin iodination and a case without any peroxidase activity.", "content": "Two patients (G2, G3) with iodine organification defect were studied. The first patient (G2), a 25-year-old women with no clinical hypothyroidism, had had her goiter for 10 years; 62% of the thyroidal iodine was released by perchlorate indicating iodine organification defect. The thyroid tissue obtained at thyroidectomy contained a normal concentration of thyroid peroxidase (I2 formation from I-) when tested after solubilization of the enzyme by trypsin and digitonin treatment of the particulate material. 1. The enzymatic activity (G2-TPO) behaved on DEAE cellulose chromatography very differently from those of hog (P-TPO) or another human goiter peroxidase (G1-TPO) (Pommier, et al., J Clin Endocrinol Metab 39: 69, 1974): the molarity of elution was 2M NaCl instead of 0.15 mM. 2. Both P-TPO and G2-TPO catalyzed iodide peroxidation (I- leads to I2) but the Km (iodide) value for G2-TPO was much lower (2.3 x 10(-2) M) when compared with that of P-TPO (3.7 x 10(-3) M) or G1-TPO (3.5 x 10(-3) M). In addition, the optimum pH for this reaction differed markedly (pH 6.1 instead of 7.9). 3. G2-TPO was poorly efficient in catalyzing the oxidation of gaiacol to tetragaiacol. 4. G2-TPO was unable to perform the iodination of non-iodinated goiter thyroglobulin whatever the pH and the iodide concentration. 5. Thyroglobulin from this goiter (G2) was almost not iodinated (0.0014%), i.e., 0.07 atoms iodine/mole thyroglobulin), and its total content in the gland was very low (0.3-4 g/1000 g wet tissue instead of 25 g). A clear discrepancy was thus shown between the euthyroid state of this patient and the total lack of iodinating activity of the isolated peroxidase. The second patient (G3), a 17-year-old man with clinical hypothyroidism, had had his goiter for 5 years. 100% of the thyroidal iodine was released by perchlorate indicating a complete iodine organification defect. The thyroid tissue obtained at thyroidectomy contained no peroxidase activity when tested before and after treatment of the particulate material by trypsin and digitonin and even in the presence of hematin. Thyroglobulin from this goiter, which was almost non-iodinated (0.0014%), was present in normal amounts in the gland (congruent to 25 g/1000 g).", "contents": "Thyroid iodine organification defects: a case with lack of thyroglobulin iodination and a case without any peroxidase activity. Two patients (G2, G3) with iodine organification defect were studied. The first patient (G2), a 25-year-old women with no clinical hypothyroidism, had had her goiter for 10 years; 62% of the thyroidal iodine was released by perchlorate indicating iodine organification defect. The thyroid tissue obtained at thyroidectomy contained a normal concentration of thyroid peroxidase (I2 formation from I-) when tested after solubilization of the enzyme by trypsin and digitonin treatment of the particulate material. 1. The enzymatic activity (G2-TPO) behaved on DEAE cellulose chromatography very differently from those of hog (P-TPO) or another human goiter peroxidase (G1-TPO) (Pommier, et al., J Clin Endocrinol Metab 39: 69, 1974): the molarity of elution was 2M NaCl instead of 0.15 mM. 2. Both P-TPO and G2-TPO catalyzed iodide peroxidation (I- leads to I2) but the Km (iodide) value for G2-TPO was much lower (2.3 x 10(-2) M) when compared with that of P-TPO (3.7 x 10(-3) M) or G1-TPO (3.5 x 10(-3) M). In addition, the optimum pH for this reaction differed markedly (pH 6.1 instead of 7.9). 3. G2-TPO was poorly efficient in catalyzing the oxidation of gaiacol to tetragaiacol. 4. G2-TPO was unable to perform the iodination of non-iodinated goiter thyroglobulin whatever the pH and the iodide concentration. 5. Thyroglobulin from this goiter (G2) was almost not iodinated (0.0014%), i.e., 0.07 atoms iodine/mole thyroglobulin), and its total content in the gland was very low (0.3-4 g/1000 g wet tissue instead of 25 g). A clear discrepancy was thus shown between the euthyroid state of this patient and the total lack of iodinating activity of the isolated peroxidase. The second patient (G3), a 17-year-old man with clinical hypothyroidism, had had his goiter for 5 years. 100% of the thyroidal iodine was released by perchlorate indicating a complete iodine organification defect. The thyroid tissue obtained at thyroidectomy contained no peroxidase activity when tested before and after treatment of the particulate material by trypsin and digitonin and even in the presence of hematin. Thyroglobulin from this goiter, which was almost non-iodinated (0.0014%), was present in normal amounts in the gland (congruent to 25 g/1000 g)."} {"id": "PMID:1262433", "title": "Improved diagnosis and management of hyper- and hypothyroidism by timing the arterial sounds.", "content": "\"Sphygmo-Recording,\" a non-invasive method for timing the arterial pulse wave contour provides an objective measure of responses to medication in patients with hyper- and hypothyroidism. The QKd interval, i.e., the interval from the onset of the QRS complex (Q) to the onset of the Korotkoff sounds (K) at the brachial artery when the sphygmomanometer cuff is at diastolic pressure (d) is the QKd interval. QKd is normally 205 +/- 12 msec. In the hyperthyroidism the QKd interval may be shortened to 110 msec. In hypothyroidism the QKd interval may be prolonged to 320 msec. Changes in QKd parallel changes in clinical status and serum total T4 and T3, measured by radioimmunoassay. QKd can be used as an objective guide to antithyroid therapy in hyperthyroidism and replacement therapy with thyroid hormone in hypothyroid individuals.", "contents": "Improved diagnosis and management of hyper- and hypothyroidism by timing the arterial sounds. \"Sphygmo-Recording,\" a non-invasive method for timing the arterial pulse wave contour provides an objective measure of responses to medication in patients with hyper- and hypothyroidism. The QKd interval, i.e., the interval from the onset of the QRS complex (Q) to the onset of the Korotkoff sounds (K) at the brachial artery when the sphygmomanometer cuff is at diastolic pressure (d) is the QKd interval. QKd is normally 205 +/- 12 msec. In the hyperthyroidism the QKd interval may be shortened to 110 msec. In hypothyroidism the QKd interval may be prolonged to 320 msec. Changes in QKd parallel changes in clinical status and serum total T4 and T3, measured by radioimmunoassay. QKd can be used as an objective guide to antithyroid therapy in hyperthyroidism and replacement therapy with thyroid hormone in hypothyroid individuals."} {"id": "PMID:1262434", "title": "Circadian rhythm of plasma renin activity in primary hyperaldosteronism.", "content": "The circadian periodicity of plasma renin activity (PRA) during continuous recumbency was determined five times in a patient with primary hyperaldosteronism. All curves were parallel with one another. There were significant elevations of PRA at 1600-2000 h, falls at 2400 h, and peaks at 0200-0800 h. This periodicity was uninfluenced by changes in baseline PRA, serum potassium concentration, salt intake, plasma volume, blood pressure, or mineralocorticoid effect. It persisted despite inability of the patient to sleep on two nights. It is suggested that the observed periodicity of renin is a true endogenous diurnal rhythm of possible central nervous system origin.", "contents": "Circadian rhythm of plasma renin activity in primary hyperaldosteronism. The circadian periodicity of plasma renin activity (PRA) during continuous recumbency was determined five times in a patient with primary hyperaldosteronism. All curves were parallel with one another. There were significant elevations of PRA at 1600-2000 h, falls at 2400 h, and peaks at 0200-0800 h. This periodicity was uninfluenced by changes in baseline PRA, serum potassium concentration, salt intake, plasma volume, blood pressure, or mineralocorticoid effect. It persisted despite inability of the patient to sleep on two nights. It is suggested that the observed periodicity of renin is a true endogenous diurnal rhythm of possible central nervous system origin."} {"id": "PMID:1262435", "title": "Craniopharyngioma: the role of insulin in promoting postoperative growth.", "content": "To elucidate the mechanism for growth following surgery in children with craniopharyngioma, serum somatomedin and prolactin levels, and plasma insulin (IRI) levels in response to oral glucose and intravenous tolbutamide, were determined in 5 and 8 children, respectively, at variable intervals following removal of the tumor. All patients had growth hormone (GH) deficiency following surgery. Seven of 8 children had normal growth (5 cm per year or greater) postoperatively for varying periods of time; 2 children continued to grow normally 6 and 8 years after surgery. Mean (+/- SE) somatomedin level was 0.78 +/- 0.1 U/ml (normal 0.4-1.5 U/ml). Serum somatomedin was normal in 4 children with normal postoperative growth and was also normal in a child who grew poorly. Mean (+/- SE) prolactin level was 6.9 +/- 3.3 ng/ml (normal 0-20 ng/ml). In 5 non-obese children with craniopharyngioma mean (+/- SE) peak IRI level was 104.4 +/- 24.4 muU/ml after oral glucose and 56.7 +/- 8.4 muU/ml after intravenous tolbutamide. These values are similar to mean (+/- SE) peak IRI levels following glucose and tolbutamide in normal children, and significantly higher (P less than 0.05) than those of idiopathic hypopituitary children. In 2 obese children with craniopharyngioma peak IRI levels were 255 and 107 muU/ml after glucose and 208 and 103 muU/ml after tolbutamide, respectively. The patient with suboptimal growth had low IRI responses to stimuli similar to hypopituitary children. Although there was a significant correlation between peak IRI levels following glucose (r = 0.63, P less than 0.025) and tolbutamide (r = 0.75, P less than 0.01) and the rates of growth of the combined data from obese and non-obese patients, no correlation was found between the growth rates of only the non-obese craniopharyngioma patients and their peak IRI levels. No significant correlation was found between mean somatomedin level and mean rate of growth. Normal postoperative growth in all children with craniopharyngioma was associated with normal serum somatomedin activity and pancreatic beta-cell responsiveness to stimuli despite GH deficiency. The results suggest that insulin may be important in the control of somatomedin and growth in these children.", "contents": "Craniopharyngioma: the role of insulin in promoting postoperative growth. To elucidate the mechanism for growth following surgery in children with craniopharyngioma, serum somatomedin and prolactin levels, and plasma insulin (IRI) levels in response to oral glucose and intravenous tolbutamide, were determined in 5 and 8 children, respectively, at variable intervals following removal of the tumor. All patients had growth hormone (GH) deficiency following surgery. Seven of 8 children had normal growth (5 cm per year or greater) postoperatively for varying periods of time; 2 children continued to grow normally 6 and 8 years after surgery. Mean (+/- SE) somatomedin level was 0.78 +/- 0.1 U/ml (normal 0.4-1.5 U/ml). Serum somatomedin was normal in 4 children with normal postoperative growth and was also normal in a child who grew poorly. Mean (+/- SE) prolactin level was 6.9 +/- 3.3 ng/ml (normal 0-20 ng/ml). In 5 non-obese children with craniopharyngioma mean (+/- SE) peak IRI level was 104.4 +/- 24.4 muU/ml after oral glucose and 56.7 +/- 8.4 muU/ml after intravenous tolbutamide. These values are similar to mean (+/- SE) peak IRI levels following glucose and tolbutamide in normal children, and significantly higher (P less than 0.05) than those of idiopathic hypopituitary children. In 2 obese children with craniopharyngioma peak IRI levels were 255 and 107 muU/ml after glucose and 208 and 103 muU/ml after tolbutamide, respectively. The patient with suboptimal growth had low IRI responses to stimuli similar to hypopituitary children. Although there was a significant correlation between peak IRI levels following glucose (r = 0.63, P less than 0.025) and tolbutamide (r = 0.75, P less than 0.01) and the rates of growth of the combined data from obese and non-obese patients, no correlation was found between the growth rates of only the non-obese craniopharyngioma patients and their peak IRI levels. No significant correlation was found between mean somatomedin level and mean rate of growth. Normal postoperative growth in all children with craniopharyngioma was associated with normal serum somatomedin activity and pancreatic beta-cell responsiveness to stimuli despite GH deficiency. The results suggest that insulin may be important in the control of somatomedin and growth in these children."} {"id": "PMID:1262436", "title": "The effect of different preparations of human growth hormone on plasma renin activity in normal males.", "content": "The effect of acute administration of 2 preparations of growth hormone (hGH) on plasma renin activity (PRA) was studied in normal volunteers. 4 IU of standard, commercially available hGH II, Kabi, Sweden) were injected im into each of four normal subjects, and the PRA was determined in the basal state and at 30, 60, 120, 180, and 240 min after injection. Free fatty acid (FFA) was determined basally and at 15 and 210 min post-injection. The study was repeated on a different day in the same group using highly purified hGH (hGH I, 4 IU) virtually free of arginine-vasopressin. Four other normal subjects received 12 IU standard hGH (hGH II, Kabi, Sweden). There was no significant difference in PRA values with 4 IU of either preparation or with 12 IU of hGH II in any of the groups, although mean PRA was elevated in two of the patients receiving 12 IU hGH II. A rise in FFA occurred in all subjects, indicating the biological activity of hGH preparations. The possible significance of these findings to the renin-angiotensin system found in acromegaly is considered.", "contents": "The effect of different preparations of human growth hormone on plasma renin activity in normal males. The effect of acute administration of 2 preparations of growth hormone (hGH) on plasma renin activity (PRA) was studied in normal volunteers. 4 IU of standard, commercially available hGH II, Kabi, Sweden) were injected im into each of four normal subjects, and the PRA was determined in the basal state and at 30, 60, 120, 180, and 240 min after injection. Free fatty acid (FFA) was determined basally and at 15 and 210 min post-injection. The study was repeated on a different day in the same group using highly purified hGH (hGH I, 4 IU) virtually free of arginine-vasopressin. Four other normal subjects received 12 IU standard hGH (hGH II, Kabi, Sweden). There was no significant difference in PRA values with 4 IU of either preparation or with 12 IU of hGH II in any of the groups, although mean PRA was elevated in two of the patients receiving 12 IU hGH II. A rise in FFA occurred in all subjects, indicating the biological activity of hGH preparations. The possible significance of these findings to the renin-angiotensin system found in acromegaly is considered."} {"id": "PMID:1262437", "title": "Adrenocortical response to marathon running.", "content": "Plasma cortisol and plasma aldosterone levels were measured before and immediately upon completion of a marathon run in 7 highly conditioned male subjects in order to evaluate the response of the adrenal cortex to physical exertion. Both cortisol and aldosterone values rose significantly in response to the stress of the muscular exertion of the 26 mile, 385 yard run.", "contents": "Adrenocortical response to marathon running. Plasma cortisol and plasma aldosterone levels were measured before and immediately upon completion of a marathon run in 7 highly conditioned male subjects in order to evaluate the response of the adrenal cortex to physical exertion. Both cortisol and aldosterone values rose significantly in response to the stress of the muscular exertion of the 26 mile, 385 yard run."} {"id": "PMID:1262438", "title": "The interaction of blood osmolality and blood volume in regulating plasma vasopressin in man.", "content": "The effect of blood volume on the osmotic control of the antidiuretic hormone, arginine vasopressin (AVP), has been studied in 18 healthy young adults. Changes in blood osmolality and/or volume were produced by each of 3 procedures--fluid deprivation, orthostasis, and hypertonic saline infusion--and the resultant changes in plasma AVP were measured by radioimmunoassay and expressed as a function of the simultaneous level of plasma osmolality. When the subjects were hydropenic and recumbent, a highly significant correlation between plasma AVP and osmolality was observed that was described by the regression equation y = 0.35 (x -281.0) where y represents the plasma AVP concentration in pg/ml and x the plasma osmolality in mosmol/kg. When these same hydropenic subjects were studied in the upright position, a maneuver that reduces intrathoracic blood volume, plasma AVP and osmolality still showed a significant correlation, but the regression equation describing this relation, y = 0.31 (x -277.8), occupied a position significantly to the left of that found during recumbency. Conversely, when the same subjects were studied during infusion of hypertonic saline, a procedure that increases blood volume, plasma AVP and osmolality again correlated significantly but the regression equation describing this relation, y = 0.32 (x -282), now occupied a position significantly to the right of that obtained during recumbent and hydropenic conditions. These results indicate that moderate increases or decreases in blood volume do influence the osmoregulation of AVP in man, but the effects are relatively small and limited to adjustments in the set of the receptor toward higher or lower levels of osmolality.", "contents": "The interaction of blood osmolality and blood volume in regulating plasma vasopressin in man. The effect of blood volume on the osmotic control of the antidiuretic hormone, arginine vasopressin (AVP), has been studied in 18 healthy young adults. Changes in blood osmolality and/or volume were produced by each of 3 procedures--fluid deprivation, orthostasis, and hypertonic saline infusion--and the resultant changes in plasma AVP were measured by radioimmunoassay and expressed as a function of the simultaneous level of plasma osmolality. When the subjects were hydropenic and recumbent, a highly significant correlation between plasma AVP and osmolality was observed that was described by the regression equation y = 0.35 (x -281.0) where y represents the plasma AVP concentration in pg/ml and x the plasma osmolality in mosmol/kg. When these same hydropenic subjects were studied in the upright position, a maneuver that reduces intrathoracic blood volume, plasma AVP and osmolality still showed a significant correlation, but the regression equation describing this relation, y = 0.31 (x -277.8), occupied a position significantly to the left of that found during recumbency. Conversely, when the same subjects were studied during infusion of hypertonic saline, a procedure that increases blood volume, plasma AVP and osmolality again correlated significantly but the regression equation describing this relation, y = 0.32 (x -282), now occupied a position significantly to the right of that obtained during recumbent and hydropenic conditions. These results indicate that moderate increases or decreases in blood volume do influence the osmoregulation of AVP in man, but the effects are relatively small and limited to adjustments in the set of the receptor toward higher or lower levels of osmolality."} {"id": "PMID:1262439", "title": "The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women.", "content": "Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary.", "contents": "The menopausal transition: analysis of LH, FSH, estradiol, and progesterone concentrations during menstrual cycles of older women. Studies of menstrual cycle length in large populations demonstrated that there is a striking increase in the variability of intermenstrual intervals just before menopause. The changes in serum concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P) during menstrual cycles in a group of perimenopausal women were compared with the findings in young normal women. In 8 women, 46-56 years old with regular cycles, cycle length was shorter and the mean E2 concentration was lower than in younger women. There was a striking increase in FSH concentration throughout the cycle while LH remained in the normal range. In 2 women, 14 cycles of variable length were studied during 2 years of the menopausal transition. In some instances, hormonal changes associated with follicular maturation and corpus luteum function occurred in the presence of high, menopausal levels of LH and FSH with a diminished secretion of E2 and P. In others vaginal bleeding occurred during a fall in serum E2 with no associated rise in P. Cycles of variable length during the menopausal transition may be due either to irregular maturation of residual follicles with diminished responsiveness to gonadotropin stimulation, or to anovulatory vaginal bleeding that may follow estrogen withdrawal without evidence of corpus luteum function. The observation of elevated FSH concentrations and normal LH levels in perimenopausal women emphasizes the complexity of the hypothalamic-pituitary-ovarian regulatory system and suggests that LH and FSH are modulated independently at the level of the pituitary."} {"id": "PMID:1262440", "title": "Triiodothyronine (T3)-binding immunoglobulins in a euthyroid woman: effects on measurement of T3 (RIA) and on T3 turnover.", "content": "A 36-year-old woman with nodular goiter, nervousness, and tachycardia was evaluated for T3 toxicosis. Her serum thyroxine level, resin T3 uptake, and thyroidal radioiodine uptake were normal. Her T3 (RIA), by a technique employing charcoal to separate bound and free T3, was reported as indeterminate due to an interfering substance; by a double-antibody method, her T3 (RIA) was 325 ng/dl. Further studies of the patient's serum revealed an abnormal T3-binding protein which misgrated in the beta-gamma globulin zone on paper electrophoresis and gel filtration chromatography (Sephadex G-200), and was precipitated from serum by rabbit anti-human Fab antibody. The gamma globulin fraction of the patient's serum, separated by a standard technique, showed strong binding activity toward [125I]T3, with an association constant of 4.1 X 10(8) 1/mole (Scatchard plot). In a similar system, labeled T4 was not bound. To avoid artefacts which this T3-binding protein might produce in assaying unextracted serum, T3 (RIA) was performed on an ethanol extract of serum and found to be 191 ng/dl, a slight elevation. However, the metabolic clearance rate of injected [125I]T3, estimated by non-compartmental analysis of the serum decay curve or by the specific activity or urinary T3, was about 16 1/day, a low value, so that the T3 production rate, 31 mug/day, was normal. The patient's symptoms disappeared with the resolution of domestic problems, and she appeared clinically euthyroid. Serum TSH was 5.0 uU/ml and antithyroglobulin titer, 1:16. A test for antibodies to thyroid microsomes was negative. We postulate that this subject was euthyroid, but had a concentration of T3-binding immunoglobulin which was sufficient to produce modest slowing of T3 turnover, borderline elevation of extractable T3 (RIA), and a major artefact in the T3 (RIA) measurement of unextracted serum. A similar abnormality may account for other instances of high T3:T4 ratios in serum.", "contents": "Triiodothyronine (T3)-binding immunoglobulins in a euthyroid woman: effects on measurement of T3 (RIA) and on T3 turnover. A 36-year-old woman with nodular goiter, nervousness, and tachycardia was evaluated for T3 toxicosis. Her serum thyroxine level, resin T3 uptake, and thyroidal radioiodine uptake were normal. Her T3 (RIA), by a technique employing charcoal to separate bound and free T3, was reported as indeterminate due to an interfering substance; by a double-antibody method, her T3 (RIA) was 325 ng/dl. Further studies of the patient's serum revealed an abnormal T3-binding protein which misgrated in the beta-gamma globulin zone on paper electrophoresis and gel filtration chromatography (Sephadex G-200), and was precipitated from serum by rabbit anti-human Fab antibody. The gamma globulin fraction of the patient's serum, separated by a standard technique, showed strong binding activity toward [125I]T3, with an association constant of 4.1 X 10(8) 1/mole (Scatchard plot). In a similar system, labeled T4 was not bound. To avoid artefacts which this T3-binding protein might produce in assaying unextracted serum, T3 (RIA) was performed on an ethanol extract of serum and found to be 191 ng/dl, a slight elevation. However, the metabolic clearance rate of injected [125I]T3, estimated by non-compartmental analysis of the serum decay curve or by the specific activity or urinary T3, was about 16 1/day, a low value, so that the T3 production rate, 31 mug/day, was normal. The patient's symptoms disappeared with the resolution of domestic problems, and she appeared clinically euthyroid. Serum TSH was 5.0 uU/ml and antithyroglobulin titer, 1:16. A test for antibodies to thyroid microsomes was negative. We postulate that this subject was euthyroid, but had a concentration of T3-binding immunoglobulin which was sufficient to produce modest slowing of T3 turnover, borderline elevation of extractable T3 (RIA), and a major artefact in the T3 (RIA) measurement of unextracted serum. A similar abnormality may account for other instances of high T3:T4 ratios in serum."} {"id": "PMID:1262441", "title": "Aldosterone metabolic clearance is normal in low-renin essential hypertension.", "content": "The possibility that an abnormality of aldosterone metabolism plays a role in the pathogenesis of low-renin essential hypertension was investigated. Normal subjects and patients with low-renin or normal-renin essential hypertension were evaluated while in balance, ingesting a diet providing 120 mEq sodium and 70 mEq potassium. Aldosterone metabolic clearances were determined by a constant infusion technique using tritium-labeled aldosterone. Aldosterone secretion rates and plasma aldosterone concentrations were measured by radioimmunoassay. Aldosterone metabolic clearance in normal subjects was 1422 +/- 69 (mean +/- SE) liters/24 hours. In patients with low-renin essential hypertension, aldosterone metabolic clearance was 1351 +/- 61 liters/24 hours, and in patients with normal-renin essential hypertension, it was 1412 +/- 66 liters/24 hours. These values were not significantly different from those of normal subjects. Although aldosterone secretion rates in both groups of hypertensive patients were within the normal range, patients with low-renin essential hypertension, under the conditions of this study, had significantly higher secretion rates than patients with normal-renin essential hypertension. We have concluded that the maintenance of plasma aldosterone in low-renin essential hypertension reflects sustained aldosterone secretion despite suppression of plasma renin activity, rather than reduced aldosterone metabolism. The maintenance of normal aldosterone secretion in low-renin essential hypertension appears to be inappropriate and is not explained by alterations of known regulatory mechanisms.", "contents": "Aldosterone metabolic clearance is normal in low-renin essential hypertension. The possibility that an abnormality of aldosterone metabolism plays a role in the pathogenesis of low-renin essential hypertension was investigated. Normal subjects and patients with low-renin or normal-renin essential hypertension were evaluated while in balance, ingesting a diet providing 120 mEq sodium and 70 mEq potassium. Aldosterone metabolic clearances were determined by a constant infusion technique using tritium-labeled aldosterone. Aldosterone secretion rates and plasma aldosterone concentrations were measured by radioimmunoassay. Aldosterone metabolic clearance in normal subjects was 1422 +/- 69 (mean +/- SE) liters/24 hours. In patients with low-renin essential hypertension, aldosterone metabolic clearance was 1351 +/- 61 liters/24 hours, and in patients with normal-renin essential hypertension, it was 1412 +/- 66 liters/24 hours. These values were not significantly different from those of normal subjects. Although aldosterone secretion rates in both groups of hypertensive patients were within the normal range, patients with low-renin essential hypertension, under the conditions of this study, had significantly higher secretion rates than patients with normal-renin essential hypertension. We have concluded that the maintenance of plasma aldosterone in low-renin essential hypertension reflects sustained aldosterone secretion despite suppression of plasma renin activity, rather than reduced aldosterone metabolism. The maintenance of normal aldosterone secretion in low-renin essential hypertension appears to be inappropriate and is not explained by alterations of known regulatory mechanisms."} {"id": "PMID:1262442", "title": "Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age.", "content": "Testosterone, estradiol, 170H-progesterone, and androstenedione (except in cord samples) concentrations were determined in cord sera (30 male and 14 female) and in peripheral sera from infants (121 male and 110 female), age 1 day to 2 years. Male and female cord serum levels of these steroids were not significantly different. In both sexes levels during the first week were lower than those in cord sera. In male infants serum testosterone and 170H-progesterone levels rose sharply in the second week of life, reached a peak at 1-2 months, and then declined to the range seen in later childhood by 6 months of age; male serum androstenedione and estradiol concentrations were higher during the first 2 months of life, but no distinct pattern of rise and fall was seen. In girls serum testosterone levels fell in the first week to the range seen throughout childhood; serum concentration of estradiol, androstenedione, and 17OH-progesterone in girls were markedly variable, with many values above the childhood range being seen, particularly in the first 6 months. These data provide further evidence of active Leydig cell function in male infants. They suggest that there is also ovarian secretion of sex steroids in some female infants in response to the elevated FSH and LH levels which are seen at this time.", "contents": "Pituitary-gonadal relations in infancy: 2. Patterns of serum gonadal steroid concentrations in man from birth to two years of age. Testosterone, estradiol, 170H-progesterone, and androstenedione (except in cord samples) concentrations were determined in cord sera (30 male and 14 female) and in peripheral sera from infants (121 male and 110 female), age 1 day to 2 years. Male and female cord serum levels of these steroids were not significantly different. In both sexes levels during the first week were lower than those in cord sera. In male infants serum testosterone and 170H-progesterone levels rose sharply in the second week of life, reached a peak at 1-2 months, and then declined to the range seen in later childhood by 6 months of age; male serum androstenedione and estradiol concentrations were higher during the first 2 months of life, but no distinct pattern of rise and fall was seen. In girls serum testosterone levels fell in the first week to the range seen throughout childhood; serum concentration of estradiol, androstenedione, and 17OH-progesterone in girls were markedly variable, with many values above the childhood range being seen, particularly in the first 6 months. These data provide further evidence of active Leydig cell function in male infants. They suggest that there is also ovarian secretion of sex steroids in some female infants in response to the elevated FSH and LH levels which are seen at this time."} {"id": "PMID:1262443", "title": "Dual sites of inhibition by metyrapone of human adrenal steroidogenesis: correlation of in vivo and in vitro studies.", "content": "In a patient with pituitary ACTH-dependent adrenal hyperplasia (AH), the standard oral metyrapone test resulted in a decrease in \"apparent 11beta-hydroxylase activity\" (-48%) accompanied by an increase in \"apparent cholesterol cleavage activity\" (+318%). When incubated adrenal mitochondria from this patient were studied, metyrapone inhibited both 11beta-hydroxylation of labeled 11-deoxycorticosterone and cleavage of labeled cholesterol, although at 0.1 and 1.0 mM metyrapone concentrations, depression of cholesterol cleavage (23 and 54%, respectively) was less than that of 11beta-hydroxylation (62 and 84%, respectively). The inhibition of cholesterol cleavage by metyrapone (26 and 62%, at 0.1 and 1.0 mM concentrations, respectively) was also demonstrable in adrenal mitochondria from a patient with hypercorticism resulting from an ACTH-independent adrenal adenoman (AA). Metyrapone administration to AA resulted in a significant depression of both 11beta-hydroxylase (-62%) and cholesterol cleavage (-36%) \"apparent activities\"; when metyrapone and ACTH were given together to this patient, however, only 11beta-hydroxylase \"apparent activity\" diminished (-26%), while cholesterol cleavage \"apparent activity\" was greatly augmented (+231%), thereby simulating the results of the standard metyrapone test in AH. These data demonstrate that metyrapone inhibits both mitochondrial reactions involved in cortisol synthesis--initial cholesterol cleavage and final 11beta-hydroxylation; these effects probably result from interference by this agent with the interaction between substrate and related cytochrome P - 450. Since ACTH has a major stimulatory effect on cholesterol cleavage but not on 11beta-hydroxylation, the outcome of metyrapone administration is thus determined by whether a change in ACTH level ensues: while 11beta-hydroxylation is inhibited by metyrapone under any circumstances, total steroid output rises when a compensatory ACTH increase overcomes metyrapone inhibition of cholesterol conversion into pregnenolone and falls when metyrapone inhibition of this reaction is unopposed.", "contents": "Dual sites of inhibition by metyrapone of human adrenal steroidogenesis: correlation of in vivo and in vitro studies. In a patient with pituitary ACTH-dependent adrenal hyperplasia (AH), the standard oral metyrapone test resulted in a decrease in \"apparent 11beta-hydroxylase activity\" (-48%) accompanied by an increase in \"apparent cholesterol cleavage activity\" (+318%). When incubated adrenal mitochondria from this patient were studied, metyrapone inhibited both 11beta-hydroxylation of labeled 11-deoxycorticosterone and cleavage of labeled cholesterol, although at 0.1 and 1.0 mM metyrapone concentrations, depression of cholesterol cleavage (23 and 54%, respectively) was less than that of 11beta-hydroxylation (62 and 84%, respectively). The inhibition of cholesterol cleavage by metyrapone (26 and 62%, at 0.1 and 1.0 mM concentrations, respectively) was also demonstrable in adrenal mitochondria from a patient with hypercorticism resulting from an ACTH-independent adrenal adenoman (AA). Metyrapone administration to AA resulted in a significant depression of both 11beta-hydroxylase (-62%) and cholesterol cleavage (-36%) \"apparent activities\"; when metyrapone and ACTH were given together to this patient, however, only 11beta-hydroxylase \"apparent activity\" diminished (-26%), while cholesterol cleavage \"apparent activity\" was greatly augmented (+231%), thereby simulating the results of the standard metyrapone test in AH. These data demonstrate that metyrapone inhibits both mitochondrial reactions involved in cortisol synthesis--initial cholesterol cleavage and final 11beta-hydroxylation; these effects probably result from interference by this agent with the interaction between substrate and related cytochrome P - 450. Since ACTH has a major stimulatory effect on cholesterol cleavage but not on 11beta-hydroxylation, the outcome of metyrapone administration is thus determined by whether a change in ACTH level ensues: while 11beta-hydroxylation is inhibited by metyrapone under any circumstances, total steroid output rises when a compensatory ACTH increase overcomes metyrapone inhibition of cholesterol conversion into pregnenolone and falls when metyrapone inhibition of this reaction is unopposed."} {"id": "PMID:1262444", "title": "The influence of age and sex on the metabolism of testosterone.", "content": "The influence of age and sex on the peripheral metabolism of testosterone was studied by giving intravenous tracers of 14C-testosterone to 21 prepubertal children (13 boys and 8 girls), 39 young adults 18-43 years old (23 men and 16 women), and 10 elderly adults 68-86 years old (6 men and 4 women). Studies were also carried out in 2 sexually immature young adults, one 18-year-old 45 XO phenotypic female with gonadal agenesis and one 18-year-old 45 XO, 46 XX mosaic female with gonadal dysgenesis; the latter was restudied after prolonged estrogen-progestagen therapy. Age and sex influences were observed only with respect to the androsterone/etiocholanolone (A/E) ratio; a sex difference in diol metabolite formation was not observed. Prepubertal children showed no sex difference in A/E ratio, which averaged 1.7 +/- 0.28 in boys and 1.9 +/- 0.42 in girls. Young adult men showed a slightly lower A/E ratio, averaging 1.5 +/- 0.10, while females showed a much greater decrease in A/E ratio, to 0.9 +/- 0.09, so that there was a highly significant (P less than .001) sex difference in this age group. The decreased averages were due to disappearance of the higher end of the ranges seen in prepubertal children; the lower limit of the ranges remained the same. Elderly adult men showed a further fall in the A/E ratio, to 1.0 +/- 0.11, and elderly women also showed a further fall, to 0.4 +/- 0.04; a highly significant (P less than .005) sex difference remained. Once again, the fall in average A/E ratio from young adults to elderly adults was due to disappearance of the higher end of the ranges in the former, the lower limits of the ranges were the same in both groups. Of the 2 sexually immature young women, one showed an A/E ratio of 1.3, just below the upper limit for young adult women, and the other showed a ratio of 1.8, well above that limit and thus typical of prepubertal girls. Estrogen-progestagen therapy of the second girl decreased the A/E ratio to 1.4, the upper limit for young adult women. It was concluded that there is a fundamental aging effect in both sexes which causes a gradual progressive decrease of the mean A/E ratio as a result of progressive disappearance of the higher individual A/E values while the lower end of the range of values remains constant; superimposed on this gradual decrease is an acute pubertal decrease in females, probably mediated by the development of the estrogen-progestagen milieu characteristic of sexually mature women.", "contents": "The influence of age and sex on the metabolism of testosterone. The influence of age and sex on the peripheral metabolism of testosterone was studied by giving intravenous tracers of 14C-testosterone to 21 prepubertal children (13 boys and 8 girls), 39 young adults 18-43 years old (23 men and 16 women), and 10 elderly adults 68-86 years old (6 men and 4 women). Studies were also carried out in 2 sexually immature young adults, one 18-year-old 45 XO phenotypic female with gonadal agenesis and one 18-year-old 45 XO, 46 XX mosaic female with gonadal dysgenesis; the latter was restudied after prolonged estrogen-progestagen therapy. Age and sex influences were observed only with respect to the androsterone/etiocholanolone (A/E) ratio; a sex difference in diol metabolite formation was not observed. Prepubertal children showed no sex difference in A/E ratio, which averaged 1.7 +/- 0.28 in boys and 1.9 +/- 0.42 in girls. Young adult men showed a slightly lower A/E ratio, averaging 1.5 +/- 0.10, while females showed a much greater decrease in A/E ratio, to 0.9 +/- 0.09, so that there was a highly significant (P less than .001) sex difference in this age group. The decreased averages were due to disappearance of the higher end of the ranges seen in prepubertal children; the lower limit of the ranges remained the same. Elderly adult men showed a further fall in the A/E ratio, to 1.0 +/- 0.11, and elderly women also showed a further fall, to 0.4 +/- 0.04; a highly significant (P less than .005) sex difference remained. Once again, the fall in average A/E ratio from young adults to elderly adults was due to disappearance of the higher end of the ranges in the former, the lower limits of the ranges were the same in both groups. Of the 2 sexually immature young women, one showed an A/E ratio of 1.3, just below the upper limit for young adult women, and the other showed a ratio of 1.8, well above that limit and thus typical of prepubertal girls. Estrogen-progestagen therapy of the second girl decreased the A/E ratio to 1.4, the upper limit for young adult women. It was concluded that there is a fundamental aging effect in both sexes which causes a gradual progressive decrease of the mean A/E ratio as a result of progressive disappearance of the higher individual A/E values while the lower end of the range of values remains constant; superimposed on this gradual decrease is an acute pubertal decrease in females, probably mediated by the development of the estrogen-progestagen milieu characteristic of sexually mature women."} {"id": "PMID:1262445", "title": "Induction of hypertriglyceridemia by a low-fat diet.", "content": "We have studied the effects of moderate dietary fat restriction on plasma triglyceride, cholesterol, glucose, and insulin response in 27 subjects. Compared with a control diet (45% fat, 40% carbohydrate [CHO], 15% protein) the low fat (higher CHO) diet (30% fat, 55% CHO, 15% protein) produced a 41% increase in fasting triglyceride level (155 +/- 17 to 219 +/- 23 mg%) with no change in fasting plasma cholesterol level. Furthermore, this increase in triglyceride levels; induced by the higher CHO content of the low fat diet, was seen in 26 out of 27 subjects. Postprandial triglyceride, glucose, and insulin levels were also higher on the low fat (higher CHO) diet. Since hypertriglyceridemia is a significant risk factor for the development of coronary heart disease, and since our data indicate that the moderate increase in dietary CHO associated with a low fat diet will elevate plasma triglyceride levels, we believe that more caution is necessary before recommending the wide-spread use of low fat diets for heart disease prevention.", "contents": "Induction of hypertriglyceridemia by a low-fat diet. We have studied the effects of moderate dietary fat restriction on plasma triglyceride, cholesterol, glucose, and insulin response in 27 subjects. Compared with a control diet (45% fat, 40% carbohydrate [CHO], 15% protein) the low fat (higher CHO) diet (30% fat, 55% CHO, 15% protein) produced a 41% increase in fasting triglyceride level (155 +/- 17 to 219 +/- 23 mg%) with no change in fasting plasma cholesterol level. Furthermore, this increase in triglyceride levels; induced by the higher CHO content of the low fat diet, was seen in 26 out of 27 subjects. Postprandial triglyceride, glucose, and insulin levels were also higher on the low fat (higher CHO) diet. Since hypertriglyceridemia is a significant risk factor for the development of coronary heart disease, and since our data indicate that the moderate increase in dietary CHO associated with a low fat diet will elevate plasma triglyceride levels, we believe that more caution is necessary before recommending the wide-spread use of low fat diets for heart disease prevention."} {"id": "PMID:1262446", "title": "Xylitol: stimulation of insulin and inhibition of glucagon responses to arginine in man.", "content": "The effect of intravenous xylitol infusions on plasma glucagon and insulin responses to intravenous arginine infusions (30 g for 45 min) or arginine \"pulses\" (4 g for 2 min) was studied in normal subjects. Intravenous infusion of arginine caused biphasic increases in plasma glucagon and insulin in all subjects studied. The increase in plasma glucagon induced by arginine infusion was significantly reduced by xylitol infusions started at 45 min before arginine infusion, irrespective of virtually unchanged blood glucose levels. Plasma insulin response to arginine was exaggerated by xylitol infusion. Repeated arginine pulses given at 30 min intervals evoked uniphasic and almost identical rises of plasma insulin and glucagon with each pulse. Intravenous xylitol infusions significantly blunted plasma glucagon responses and augumented the plasma insulin response to arginine pulses, despite only slight elevations of plasma glucose. These results suggest that xylitol has an inhibitory effect on both basal and arginine-stimulated glucagon secretion, while it enhances insulin secretion.", "contents": "Xylitol: stimulation of insulin and inhibition of glucagon responses to arginine in man. The effect of intravenous xylitol infusions on plasma glucagon and insulin responses to intravenous arginine infusions (30 g for 45 min) or arginine \"pulses\" (4 g for 2 min) was studied in normal subjects. Intravenous infusion of arginine caused biphasic increases in plasma glucagon and insulin in all subjects studied. The increase in plasma glucagon induced by arginine infusion was significantly reduced by xylitol infusions started at 45 min before arginine infusion, irrespective of virtually unchanged blood glucose levels. Plasma insulin response to arginine was exaggerated by xylitol infusion. Repeated arginine pulses given at 30 min intervals evoked uniphasic and almost identical rises of plasma insulin and glucagon with each pulse. Intravenous xylitol infusions significantly blunted plasma glucagon responses and augumented the plasma insulin response to arginine pulses, despite only slight elevations of plasma glucose. These results suggest that xylitol has an inhibitory effect on both basal and arginine-stimulated glucagon secretion, while it enhances insulin secretion."} {"id": "PMID:1262447", "title": "Nocturnal elevation of plasma melatonin and urinary 5-hydroxyindoleacetic acid in young men: attempts at modification by brief changes in environmental lighting and sleep and by autonomic drugs.", "content": "In order to determine whether the human pattern of circulating melatonin resembles that previously described in lower animals, men 19-32 years old were exposed to a light-dark cycle with 14 hours of light per day (L:D 14:10). In whites and blacks, nocturnal (dark phase, sleeping) melatonin levels were almost always elevated to 0.05-0.1 ng/ml plasma compared with lower or undetectable levels during the day, measured by the tadpole bioassay. Thin-layer migration of bioactive material was identical to that for melatonin standard. A rhythm with nocturnal elevation of urinary 5-hydroxyindoleacetic acid (5-HIAA) was observed. Nocturnal (sleep phase) rise in blood melatonin (but not urinary 5-HIAA) continued during 21/2 day-night cycle lengths after the onset of constant light. Though the dark phase plasma melatonin rise was less marked after reversal of the sleep-wake cycle (no change in the light cycle), dark phase rise in urinary 5-HIAA continued. Though marked cardiovascular and other effects were produced by intravenous isoproterenol or scopolamine, no definite effect on melatonin levels was observed after either drug during the light phase in waking subjects.", "contents": "Nocturnal elevation of plasma melatonin and urinary 5-hydroxyindoleacetic acid in young men: attempts at modification by brief changes in environmental lighting and sleep and by autonomic drugs. In order to determine whether the human pattern of circulating melatonin resembles that previously described in lower animals, men 19-32 years old were exposed to a light-dark cycle with 14 hours of light per day (L:D 14:10). In whites and blacks, nocturnal (dark phase, sleeping) melatonin levels were almost always elevated to 0.05-0.1 ng/ml plasma compared with lower or undetectable levels during the day, measured by the tadpole bioassay. Thin-layer migration of bioactive material was identical to that for melatonin standard. A rhythm with nocturnal elevation of urinary 5-hydroxyindoleacetic acid (5-HIAA) was observed. Nocturnal (sleep phase) rise in blood melatonin (but not urinary 5-HIAA) continued during 21/2 day-night cycle lengths after the onset of constant light. Though the dark phase plasma melatonin rise was less marked after reversal of the sleep-wake cycle (no change in the light cycle), dark phase rise in urinary 5-HIAA continued. Though marked cardiovascular and other effects were produced by intravenous isoproterenol or scopolamine, no definite effect on melatonin levels was observed after either drug during the light phase in waking subjects."} {"id": "PMID:1262448", "title": "Obesity and oligomenorrhea are associated with hyperandrogenism independent of hirsutism.", "content": "Obesity, oligomenorrhea, and hirsutism are frequently associated with high plasma androgen levels and/or low testosterone-binding globulin (TEBG) levels. Studied have been undertaken to determine the extent to which each of these clinical features may be related to this hormonal profile. Indexes of plasma free (unbound) androgen levels were focused upon because this fraction appears to be the biologically active portion of the plasma androgens. The hormonal profile was normal in women with either obesity or oligomenorrhea alone and abnormal in those with severe hirsutism alone. On striking new finding was that subjects with the combination of obesity and oligomenorrhea had elevated plasma total and free androgens and depressed TEBG even in the absence of hirsutism. Furthermore, the androgen levels were higher in obese oligomenorrheic women with mild hirsutism than in severely hirsute women who were not obese. Plasma estradiol concentrations were normal in these obese women. A simple explanation for elevated free plasma androgen levels in obese women who were oligomenorrheic yet had little if any hirsutism is not possible. The data are compatible with the concept that obesity is a variably expressed manifestation of slightly elevated plasma free androgen levels or that obesity is an incidental finding which somehow blunts the effect of high androgen levels on hair follicles. Regardless of the explanation, oligomenorrheic obese women must be suspected of having high androgen production even in the absence of hirsutism.", "contents": "Obesity and oligomenorrhea are associated with hyperandrogenism independent of hirsutism. Obesity, oligomenorrhea, and hirsutism are frequently associated with high plasma androgen levels and/or low testosterone-binding globulin (TEBG) levels. Studied have been undertaken to determine the extent to which each of these clinical features may be related to this hormonal profile. Indexes of plasma free (unbound) androgen levels were focused upon because this fraction appears to be the biologically active portion of the plasma androgens. The hormonal profile was normal in women with either obesity or oligomenorrhea alone and abnormal in those with severe hirsutism alone. On striking new finding was that subjects with the combination of obesity and oligomenorrhea had elevated plasma total and free androgens and depressed TEBG even in the absence of hirsutism. Furthermore, the androgen levels were higher in obese oligomenorrheic women with mild hirsutism than in severely hirsute women who were not obese. Plasma estradiol concentrations were normal in these obese women. A simple explanation for elevated free plasma androgen levels in obese women who were oligomenorrheic yet had little if any hirsutism is not possible. The data are compatible with the concept that obesity is a variably expressed manifestation of slightly elevated plasma free androgen levels or that obesity is an incidental finding which somehow blunts the effect of high androgen levels on hair follicles. Regardless of the explanation, oligomenorrheic obese women must be suspected of having high androgen production even in the absence of hirsutism."} {"id": "PMID:1262449", "title": "Circadian rhythms in gonadotropin excretion in prepubertal and pubertal children.", "content": "Timed urinary collections were obtained during sleep and waking hours from 27 prepubertal children ranging in age from 2-12 years and from 13 subjects in various stages of puberty, 12-18 years old. The urine samples were extracted with acetone and introduced into FSH and LH radioimmunoassays. Results of the study indicate a significant nocturnal augmentation of LH secretion in pubertal subjects, confirming existing reports using blood sampling techniques. Increased LH and FSH excretion during sleep was also found in prepubertal children.", "contents": "Circadian rhythms in gonadotropin excretion in prepubertal and pubertal children. Timed urinary collections were obtained during sleep and waking hours from 27 prepubertal children ranging in age from 2-12 years and from 13 subjects in various stages of puberty, 12-18 years old. The urine samples were extracted with acetone and introduced into FSH and LH radioimmunoassays. Results of the study indicate a significant nocturnal augmentation of LH secretion in pubertal subjects, confirming existing reports using blood sampling techniques. Increased LH and FSH excretion during sleep was also found in prepubertal children."} {"id": "PMID:1262450", "title": "Quantitative determination of sex hormone-binding globulin capacity in the plasma of normal and diabetic pregnancies.", "content": "Sex hormone-binding globulin (SHBG) capacity was measured in a longitudinal study in plasma samples from normal subjects, diabetics, and gestational diabetics and throughout pregnancy, together with unconjugated plasma estradiol. In normal women SHBG capacity (expressed in ng DHT bound per ml of plasma) increased from 23.7 +/- 13.7 (SD) in the 5-8th week period, to 74.5 +/- 20.7 in the 17-20th week period, and to 102 +/- 24 in the 37-40th week period. In diabetics the SHBG capacity for the same periods of time were respectively: 25.3 +/- 17.2, 83.1 +/- 29.1, and 111.6 +/- 22.6. Plasma levels of unconjugated estradiol were 55% higher in the diabetics than in the normal subjects in the second half of gestation, as reported in detail in another publication. From the imbalance between the close to normal SHBG capacity and the higher plasma levels of unconjugated estradiol in the diabetics, it is suggested that the unbound, i.e., metabolically active, fraction of plasma estradiol reaches higher levels in diabetics than in normal subjects in the second half of gestation.", "contents": "Quantitative determination of sex hormone-binding globulin capacity in the plasma of normal and diabetic pregnancies. Sex hormone-binding globulin (SHBG) capacity was measured in a longitudinal study in plasma samples from normal subjects, diabetics, and gestational diabetics and throughout pregnancy, together with unconjugated plasma estradiol. In normal women SHBG capacity (expressed in ng DHT bound per ml of plasma) increased from 23.7 +/- 13.7 (SD) in the 5-8th week period, to 74.5 +/- 20.7 in the 17-20th week period, and to 102 +/- 24 in the 37-40th week period. In diabetics the SHBG capacity for the same periods of time were respectively: 25.3 +/- 17.2, 83.1 +/- 29.1, and 111.6 +/- 22.6. Plasma levels of unconjugated estradiol were 55% higher in the diabetics than in the normal subjects in the second half of gestation, as reported in detail in another publication. From the imbalance between the close to normal SHBG capacity and the higher plasma levels of unconjugated estradiol in the diabetics, it is suggested that the unbound, i.e., metabolically active, fraction of plasma estradiol reaches higher levels in diabetics than in normal subjects in the second half of gestation."} {"id": "PMID:1262451", "title": "Citrobacter diversus isolated from clinical material.", "content": "Forty-seven strains of Citrobacter diversus were isolated during a 12-month period from clinical material obtained from patients in a general hospital in Israel. The majority of cultures (38) were recovered from urine and wound discharges. There was one case of septicemia. The biochemical reactions of all cultures were typical for this species, except one that was anaerogenic, and they could be divided into five biotypes (a through e). Thirty-nine strains were identified serologically and found to belong to one of seven O groups described by Gross and Rowe (1974). All cultures were sensitive to tetracycline and nalidixic acid. All strains were resistant to carbenicillin and ampicillin and produced beta-lactamase.", "contents": "Citrobacter diversus isolated from clinical material. Forty-seven strains of Citrobacter diversus were isolated during a 12-month period from clinical material obtained from patients in a general hospital in Israel. The majority of cultures (38) were recovered from urine and wound discharges. There was one case of septicemia. The biochemical reactions of all cultures were typical for this species, except one that was anaerogenic, and they could be divided into five biotypes (a through e). Thirty-nine strains were identified serologically and found to belong to one of seven O groups described by Gross and Rowe (1974). All cultures were sensitive to tetracycline and nalidixic acid. All strains were resistant to carbenicillin and ampicillin and produced beta-lactamase."} {"id": "PMID:1262452", "title": "Application of a gloved-hand model for multiparameter measurements of skin-degerming activity.", "content": "The application of an established gloved-hand model to multiparameter measurements of skin-degerming activity is described. In particular, appropriate experimental designs are illustrated which allow characterization of performance of topical skin-cleansing preparations in terms of rapid, sustained, cummulative, and persistent skin-degerming effects on the hand. Single-contact studies were used to define the degerming activity profiles of selected commercial surgical scrub preparations, and to establish the optimal post-treatment sampling interval for individual preparations. Rapid and sustained skin-degerming effects were measured and contrasted. Rapid skin-degerming activity, iodophor preparation. Sustained skin-degerming activity, namely, that occurring on the gloved hand during a postcontact interval, was shown and characterized for two hexachlorophene preparations. Multiple-contact studies with a 3% hexachlorophene preparations were used to illustrate cummulative and persistent skin-degerming effects. Cummulative skin-degerming activity was demonstrated in terms of progressive bacterial reductions after repeated contacts within a single day. Presistent skin-degerming activity was shown in terms of the profile of daily pretreatment bacterial counts after multiple contacts over successive days. Uniformity of treatment response was established for a broad range of pretreatment bacterial counts extending from approximatley log 4 to log 7 per hand. The importance of pretreatment bacterial count measurement and of adequate neutralization of hand extract samples is stressed. A randomized-hand experimental design is discussed relative to its versatility and amenability to statistical analysis.", "contents": "Application of a gloved-hand model for multiparameter measurements of skin-degerming activity. The application of an established gloved-hand model to multiparameter measurements of skin-degerming activity is described. In particular, appropriate experimental designs are illustrated which allow characterization of performance of topical skin-cleansing preparations in terms of rapid, sustained, cummulative, and persistent skin-degerming effects on the hand. Single-contact studies were used to define the degerming activity profiles of selected commercial surgical scrub preparations, and to establish the optimal post-treatment sampling interval for individual preparations. Rapid and sustained skin-degerming effects were measured and contrasted. Rapid skin-degerming activity, iodophor preparation. Sustained skin-degerming activity, namely, that occurring on the gloved hand during a postcontact interval, was shown and characterized for two hexachlorophene preparations. Multiple-contact studies with a 3% hexachlorophene preparations were used to illustrate cummulative and persistent skin-degerming effects. Cummulative skin-degerming activity was demonstrated in terms of progressive bacterial reductions after repeated contacts within a single day. Presistent skin-degerming activity was shown in terms of the profile of daily pretreatment bacterial counts after multiple contacts over successive days. Uniformity of treatment response was established for a broad range of pretreatment bacterial counts extending from approximatley log 4 to log 7 per hand. The importance of pretreatment bacterial count measurement and of adequate neutralization of hand extract samples is stressed. A randomized-hand experimental design is discussed relative to its versatility and amenability to statistical analysis."} {"id": "PMID:1262453", "title": "Differential identification of Mycobaterium szulgai and other scotochromogenic mycobateria.", "content": "Strains of scotochromogenic mycobacteria were studied by using numerical taxonomy methods in an attempt to more clearly define Mycobacterium szulgai and to find tests useful in identifying the species. In this study all strains of M. szulgai were strong reducers of nitrate, were slow in hydrolyzing Tween 80, and gave a high semiquantitative catalase reaction. Results obtained indicate that the use of increased pigmentation after 1 h of light exposure at 25 C and that the use of arylsulfatase activity are of questionable diagnostic value in separating the species from other scotochrompgenic mycobacteria.", "contents": "Differential identification of Mycobaterium szulgai and other scotochromogenic mycobateria. Strains of scotochromogenic mycobacteria were studied by using numerical taxonomy methods in an attempt to more clearly define Mycobacterium szulgai and to find tests useful in identifying the species. In this study all strains of M. szulgai were strong reducers of nitrate, were slow in hydrolyzing Tween 80, and gave a high semiquantitative catalase reaction. Results obtained indicate that the use of increased pigmentation after 1 h of light exposure at 25 C and that the use of arylsulfatase activity are of questionable diagnostic value in separating the species from other scotochrompgenic mycobacteria."} {"id": "PMID:1262454", "title": "Halophilic Vibrio species isolated from blood cultures.", "content": "The Special Bacteriology Section of the Center for Disease Control has received 38 cultures of a halophilic bacterium which apparently unnamed. On the basis of the minimal characteristics of Vibrio species proposed by Hugh and Sakazaki, this bacterium belongs to the genus Vibrio. The unnamed species can be differentiated from Vibro parahaemolyticus by a lower tolerance for sodium chloride (NaC1) and the fermentation of lactose. The failure to ferment sucrose is an additional characteristic which differentiates these organisms from V. alginolyticus. Of 33 unnamed species strains tested, all were sensitive to penicillin, ampicillin, carbenicillin, cephalothin, chlorapmphenicol, gentamicin, tetracycline, rifampin, nitrofurantoin, and sulfisoxazole by agar diffusion and agar dilution tests. The sources of isolation of the cultures of the unnamed species suggest that it is a clinically important organism. Twenty strains were isolated remaining cultures were isolated from localized infections of the extremities. In contrast, only 2 of 60 cultures of V. parahaemolyticus and V. alginolyticus received in our laboratory as human isolates from extra-intestinal sources were isolated from blood.", "contents": "Halophilic Vibrio species isolated from blood cultures. The Special Bacteriology Section of the Center for Disease Control has received 38 cultures of a halophilic bacterium which apparently unnamed. On the basis of the minimal characteristics of Vibrio species proposed by Hugh and Sakazaki, this bacterium belongs to the genus Vibrio. The unnamed species can be differentiated from Vibro parahaemolyticus by a lower tolerance for sodium chloride (NaC1) and the fermentation of lactose. The failure to ferment sucrose is an additional characteristic which differentiates these organisms from V. alginolyticus. Of 33 unnamed species strains tested, all were sensitive to penicillin, ampicillin, carbenicillin, cephalothin, chlorapmphenicol, gentamicin, tetracycline, rifampin, nitrofurantoin, and sulfisoxazole by agar diffusion and agar dilution tests. The sources of isolation of the cultures of the unnamed species suggest that it is a clinically important organism. Twenty strains were isolated remaining cultures were isolated from localized infections of the extremities. In contrast, only 2 of 60 cultures of V. parahaemolyticus and V. alginolyticus received in our laboratory as human isolates from extra-intestinal sources were isolated from blood."} {"id": "PMID:1262455", "title": "Mycobacterium resembling Mycobacterium fortuitum that produces brown pigment.", "content": "Two cultures of acid-fast bacilli with characteristics most closely resembling those of Mycobacterium fortuitum were recovered as casual isolates from sputa of a patient with an apparent brochogenic tumor. One of the cultures was consistenly cream colored to rosy buff. The other, however, changed from buff to rust to dark brown and had the gross appearance of a fungus culture.", "contents": "Mycobacterium resembling Mycobacterium fortuitum that produces brown pigment. Two cultures of acid-fast bacilli with characteristics most closely resembling those of Mycobacterium fortuitum were recovered as casual isolates from sputa of a patient with an apparent brochogenic tumor. One of the cultures was consistenly cream colored to rosy buff. The other, however, changed from buff to rust to dark brown and had the gross appearance of a fungus culture."} {"id": "PMID:1262456", "title": "Evaluation of beckman antistreptolysin O and antideoxyribonuclease B (ASO/ADB) test kit.", "content": "The Beckman antistreptolysin O kit agreed within one-dilution increment for 70% of the specimens tested. The antideoxyribonuclease B kit agreed within onedilution increment for 96% of the specimens tested.", "contents": "Evaluation of beckman antistreptolysin O and antideoxyribonuclease B (ASO/ADB) test kit. The Beckman antistreptolysin O kit agreed within one-dilution increment for 70% of the specimens tested. The antideoxyribonuclease B kit agreed within onedilution increment for 96% of the specimens tested."} {"id": "PMID:1262457", "title": "Improved method for production of attenuated Venezuelan equine encephalomyelitis (TC-83 strain) vaccine.", "content": "Primary chicken embryo cell cultures were evaluated a s an alternate cell system for the production of attenuated Venezuelan equine encephalomyelitis (TC-83 strain) vaccine. The TC-83 strain virus was shown to remain stable during 10 serial passages in chicken embryo cell culture with regard to plaque size and morphology, virus yield, potency, and virulence for mice and hamsters.", "contents": "Improved method for production of attenuated Venezuelan equine encephalomyelitis (TC-83 strain) vaccine. Primary chicken embryo cell cultures were evaluated a s an alternate cell system for the production of attenuated Venezuelan equine encephalomyelitis (TC-83 strain) vaccine. The TC-83 strain virus was shown to remain stable during 10 serial passages in chicken embryo cell culture with regard to plaque size and morphology, virus yield, potency, and virulence for mice and hamsters."} {"id": "PMID:1262458", "title": "Distribution, blood transport, and degradation of antidiuretic hormone in man.", "content": "The distribution, blood transport, and metabolic clearance of physiological concentrations of antidiuretic hormone were studied in 10 hydrated normal subjects with radioiodinated arginine vasopressin (125I-AVP). At 37 degrees C no binding of 125I-AVP to plasma proteins could be demonstrated, but some metabolites were associated with plasma proteins. 125I-AVP was rapidly distributed into a space approximating the extracellular fluid volume. Metabolic breakdown products became demonstrable within minutes after injection. The mean metabolic clearance rate of 125I-AVP was 4.1 ml/min/kg and the mean plasma half-life 24.1 min. Renal clearance had a mean value of 80 ml/min and accounted for 27% of the total metabolic clearance. It is concluded that in man antidiuretic hormone circulates as a free (non-protein bound) peptide, diffuses readily into the extracellular fluid space, and is metabolized within minutes. A plasma half-life of 24 min is consistent with the duration of antidiuresis after hormone administration or release.", "contents": "Distribution, blood transport, and degradation of antidiuretic hormone in man. The distribution, blood transport, and metabolic clearance of physiological concentrations of antidiuretic hormone were studied in 10 hydrated normal subjects with radioiodinated arginine vasopressin (125I-AVP). At 37 degrees C no binding of 125I-AVP to plasma proteins could be demonstrated, but some metabolites were associated with plasma proteins. 125I-AVP was rapidly distributed into a space approximating the extracellular fluid volume. Metabolic breakdown products became demonstrable within minutes after injection. The mean metabolic clearance rate of 125I-AVP was 4.1 ml/min/kg and the mean plasma half-life 24.1 min. Renal clearance had a mean value of 80 ml/min and accounted for 27% of the total metabolic clearance. It is concluded that in man antidiuretic hormone circulates as a free (non-protein bound) peptide, diffuses readily into the extracellular fluid space, and is metabolized within minutes. A plasma half-life of 24 min is consistent with the duration of antidiuresis after hormone administration or release."} {"id": "PMID:1262459", "title": "An anomaly of insulin removal in perfused livers of obese-hyperglycemic (ob/ob) mice.", "content": "Obese-hyperglycemic (ob/ob) mice have the interesting feature of being hyperinsulinemic, thus having some characteristics in common with human maturity-onset diabetics. As the cause of hyperinsulinemia in these mice is not established, and as the liver is known to play a role in determining the amount of hormone that reaches the periphery, it was hypothesized that an anomaly in the hepatic handling of insulin might prevail in obese-hyperglycemic mice. Immunoreactive insulin was therefore measured in the perfusate before and after a single passage through perfused livers of lean and ob/ob mice, permitting. It was found that the removal of insulin by livers of lean mice increased with increasing concentrations of the hormone in the portal vein. The removal process had a limited capacity, however, and as a consequence the percentage of hormone removed by the liver actually decreased when portal insulin concentrations increased. Insulin removal by livers of ob/ob mice had qualitatively the same characteristics but was considerably less efficient than in normal livers. Due to this, more insulin was found in the perfusate leaving the liver of ob/9b mice than in that of controls, at any insulin concentration tested. These observations suggest that in obese-hyperglycemic mice more of the hormone may reach the periphery and thus contribute to hyperinsulinemia. The present study further suggests that the anomaly of insulin removal observed in perfused livers of ob/ob mice might be secondary to hyperinsulinemia, since it was partly corrected upon artificially decreasing the circulating levels of insulin (e.g. via a fast, anti-insulin serum, or streptozotocin treatment) before perfusion. The characteristics of hepatic insulin removal reported in this study, as well as the differences observed between livers of lean and ob/ob mice, may reflect changes in membrane insulin receptors and/or in processes responsible for the degradation of the horomone.", "contents": "An anomaly of insulin removal in perfused livers of obese-hyperglycemic (ob/ob) mice. Obese-hyperglycemic (ob/ob) mice have the interesting feature of being hyperinsulinemic, thus having some characteristics in common with human maturity-onset diabetics. As the cause of hyperinsulinemia in these mice is not established, and as the liver is known to play a role in determining the amount of hormone that reaches the periphery, it was hypothesized that an anomaly in the hepatic handling of insulin might prevail in obese-hyperglycemic mice. Immunoreactive insulin was therefore measured in the perfusate before and after a single passage through perfused livers of lean and ob/ob mice, permitting. It was found that the removal of insulin by livers of lean mice increased with increasing concentrations of the hormone in the portal vein. The removal process had a limited capacity, however, and as a consequence the percentage of hormone removed by the liver actually decreased when portal insulin concentrations increased. Insulin removal by livers of ob/ob mice had qualitatively the same characteristics but was considerably less efficient than in normal livers. Due to this, more insulin was found in the perfusate leaving the liver of ob/9b mice than in that of controls, at any insulin concentration tested. These observations suggest that in obese-hyperglycemic mice more of the hormone may reach the periphery and thus contribute to hyperinsulinemia. The present study further suggests that the anomaly of insulin removal observed in perfused livers of ob/ob mice might be secondary to hyperinsulinemia, since it was partly corrected upon artificially decreasing the circulating levels of insulin (e.g. via a fast, anti-insulin serum, or streptozotocin treatment) before perfusion. The characteristics of hepatic insulin removal reported in this study, as well as the differences observed between livers of lean and ob/ob mice, may reflect changes in membrane insulin receptors and/or in processes responsible for the degradation of the horomone."} {"id": "PMID:1262460", "title": "Clearance and acid-stimulating action of human big and little gastrins in duodenal ulcer subjects.", "content": "Acid-stimulating action and clearance of pure natural human big gastriin (HG-34-I) and little gastrin (HG-17-I) were assessed in four male subjects with inactive duodenal ulcer (DU) disease. Disappearance half-times for HG-17-I after intravenous infusion (5.2 min) or rapid intravenous injection (6.4 min) were six to eight times shorter than those for HG-34-I (41.5 and 37.8 min, respectively). Studies of clearance of synthetic human little gastrin (HG-17-I) were performed in three of these same four DU subjects, eight additional male DU subjects, and eleven normal male subjects. The disappearance halftime of synthetic HG-17-I averaged 6.2 min in both the DU subjects and the normal subjects. These data suggest that clearance of exogenous gastrin is not altered in patients with DU. Acid secretion in response to rapid intravenous injection of HG-34-I reached a higher peak and lasted longer than in response to an equimolar dose of HG-17-I; the total response to HG-34-I was about three times that to HG-17-I. During constant intravenous infusion, acid responses to equimolar exogenous doses of the two peptides were similar but the increment in molar concentration of circulating gastrin was six to eight times greater with HG-34-I than with HG-17-I. Chromatography of serum obtained during infusions of HG-34-I revealed no evidence of conversion to HG-17-I, nor was there any increase in circulating G-34 activity during infusions of HG-17-I. The increment in serum gastrin concentration required to produce half-maximal stimulation of gastric acid secretion (D50) was estimated in each subject for each gastrin from curves relating acid secretion to change in serum gastrin concentration produced by infusion of these peptides. After instilling peptone solution into the stomach, acid secretion was measured by intragastric titration, and increases in circulating G-17 and G-34 were determined by chromatography and radioimmunoassay of serum. Increases in circulating G-17 and G-34 in response to the peptone meal, taken together, were equivalent to 1.5 times the D50 determined from infusions of G-34 and G-17. Acid secretion during the same time period averaged 55% of maximal rates. Although G-34 comprised approximately three-fourths of the total molar concentration of circulating gastrin after stimulation, it was estimated to contribute less than half of the acid-stimulating activity.", "contents": "Clearance and acid-stimulating action of human big and little gastrins in duodenal ulcer subjects. Acid-stimulating action and clearance of pure natural human big gastriin (HG-34-I) and little gastrin (HG-17-I) were assessed in four male subjects with inactive duodenal ulcer (DU) disease. Disappearance half-times for HG-17-I after intravenous infusion (5.2 min) or rapid intravenous injection (6.4 min) were six to eight times shorter than those for HG-34-I (41.5 and 37.8 min, respectively). Studies of clearance of synthetic human little gastrin (HG-17-I) were performed in three of these same four DU subjects, eight additional male DU subjects, and eleven normal male subjects. The disappearance halftime of synthetic HG-17-I averaged 6.2 min in both the DU subjects and the normal subjects. These data suggest that clearance of exogenous gastrin is not altered in patients with DU. Acid secretion in response to rapid intravenous injection of HG-34-I reached a higher peak and lasted longer than in response to an equimolar dose of HG-17-I; the total response to HG-34-I was about three times that to HG-17-I. During constant intravenous infusion, acid responses to equimolar exogenous doses of the two peptides were similar but the increment in molar concentration of circulating gastrin was six to eight times greater with HG-34-I than with HG-17-I. Chromatography of serum obtained during infusions of HG-34-I revealed no evidence of conversion to HG-17-I, nor was there any increase in circulating G-34 activity during infusions of HG-17-I. The increment in serum gastrin concentration required to produce half-maximal stimulation of gastric acid secretion (D50) was estimated in each subject for each gastrin from curves relating acid secretion to change in serum gastrin concentration produced by infusion of these peptides. After instilling peptone solution into the stomach, acid secretion was measured by intragastric titration, and increases in circulating G-17 and G-34 were determined by chromatography and radioimmunoassay of serum. Increases in circulating G-17 and G-34 in response to the peptone meal, taken together, were equivalent to 1.5 times the D50 determined from infusions of G-34 and G-17. Acid secretion during the same time period averaged 55% of maximal rates. Although G-34 comprised approximately three-fourths of the total molar concentration of circulating gastrin after stimulation, it was estimated to contribute less than half of the acid-stimulating activity."} {"id": "PMID:1262461", "title": "Evidence for enhanced distal tubule sodium reabsorption in chronic salt-depleted dogs.", "content": "In order to assess the renal tubular site(s) at which sodium reabsorption is enhanced in chronic sodium-depletion, seven normal dogs, six salt-depleted dogs, and three normal dogs receiving aldosterone were studied during a steady-state water diuresis under Pentothal anesthesia and during progressive hypotonic saline diuresis. For both maintenance of the water diuresis and progressive hypotonic saline diuresis 0.45% NaCl was used. During the steady state water diuresis delivery of sodium to the diluting segment of the nephron as approximated by solute-free water clearance + sodium clearance/glomerular filtration rate (CH2O + CNa/GFR) was significantly lower in salt-depleted dogs compared to normal dogs with or without aldosterone. During progressive hypotonic saline infusion fractional free water excretion (CH2O/GFR) was similar in all three groups as CH2O + CNa/GFR increased up to 12-14 ml/min-100 ml GFR. Thereafter, CH2O/GFR continued to rise in virtually a straight line in salt-depleted dogs but leveled off in normal dogs with or without aldosterone. These data demonstrate that enhanced sodium reabsorption in the diluting segment of the nephron is an important determinant of the renal sodium retention in chronic extracellular volume contraction in dogs in addition to confirming the presence of increased proximal tubule sodium reabsorption in these animals.", "contents": "Evidence for enhanced distal tubule sodium reabsorption in chronic salt-depleted dogs. In order to assess the renal tubular site(s) at which sodium reabsorption is enhanced in chronic sodium-depletion, seven normal dogs, six salt-depleted dogs, and three normal dogs receiving aldosterone were studied during a steady-state water diuresis under Pentothal anesthesia and during progressive hypotonic saline diuresis. For both maintenance of the water diuresis and progressive hypotonic saline diuresis 0.45% NaCl was used. During the steady state water diuresis delivery of sodium to the diluting segment of the nephron as approximated by solute-free water clearance + sodium clearance/glomerular filtration rate (CH2O + CNa/GFR) was significantly lower in salt-depleted dogs compared to normal dogs with or without aldosterone. During progressive hypotonic saline infusion fractional free water excretion (CH2O/GFR) was similar in all three groups as CH2O + CNa/GFR increased up to 12-14 ml/min-100 ml GFR. Thereafter, CH2O/GFR continued to rise in virtually a straight line in salt-depleted dogs but leveled off in normal dogs with or without aldosterone. These data demonstrate that enhanced sodium reabsorption in the diluting segment of the nephron is an important determinant of the renal sodium retention in chronic extracellular volume contraction in dogs in addition to confirming the presence of increased proximal tubule sodium reabsorption in these animals."} {"id": "PMID:1262462", "title": "Mixed lymphocyte cultures in rheumatoid arthritis.", "content": "Random one-way microtiter mixed lymphocyte cultures between 43 rheumatoid arthritis (RA) patients and 45 controls consisting of 26 normal subjects and 19 miscellaneous non-RA patients were performed and results were evaluated as relative responses. Low responses (consisting of relative response less than 38%) were found in 31 out of 43 RA patients in cultures against eight of the RA stimulators. The remaining 35 RA stimulators tested yielded only normal mixed lymphocyte culture reactions. The same RA patients used as responders never produced low responses when stimulated by non-RA lymphocytes. But six of the control subjects gave low responses to two RA stimulators. The low responses did not appear to correlate with intake of aspirin, prednisolone, or gold salts, nor could they be reproduced by addition of RA serum of 7S or 19S fractions thereof containing either polyclonal or monoclonal rheumatoid factors. Short-term culture and washing before mixing with the allogeneic cells did not change the low responses suggesting that in vivo bound autoantibodies against lymphocyte receptors were not involved. Study of the inheritance of HLA and mixed lymphocyte culture determinants in the family of patient A. C. who most frequently elicited low responses indicated she was homozygous for a lymphocyte-defined determinant which has been called R. The low responses to A. C. could be interpreted as typing responses based on sharing of the same or of a similar lymphocyte-defined determinant. This gene appears to be increased in patients with RA with respect to non-RA controls and may reflect an association of genes within the HLA chromosomal region leading to predisposition for the development of RA.", "contents": "Mixed lymphocyte cultures in rheumatoid arthritis. Random one-way microtiter mixed lymphocyte cultures between 43 rheumatoid arthritis (RA) patients and 45 controls consisting of 26 normal subjects and 19 miscellaneous non-RA patients were performed and results were evaluated as relative responses. Low responses (consisting of relative response less than 38%) were found in 31 out of 43 RA patients in cultures against eight of the RA stimulators. The remaining 35 RA stimulators tested yielded only normal mixed lymphocyte culture reactions. The same RA patients used as responders never produced low responses when stimulated by non-RA lymphocytes. But six of the control subjects gave low responses to two RA stimulators. The low responses did not appear to correlate with intake of aspirin, prednisolone, or gold salts, nor could they be reproduced by addition of RA serum of 7S or 19S fractions thereof containing either polyclonal or monoclonal rheumatoid factors. Short-term culture and washing before mixing with the allogeneic cells did not change the low responses suggesting that in vivo bound autoantibodies against lymphocyte receptors were not involved. Study of the inheritance of HLA and mixed lymphocyte culture determinants in the family of patient A. C. who most frequently elicited low responses indicated she was homozygous for a lymphocyte-defined determinant which has been called R. The low responses to A. C. could be interpreted as typing responses based on sharing of the same or of a similar lymphocyte-defined determinant. This gene appears to be increased in patients with RA with respect to non-RA controls and may reflect an association of genes within the HLA chromosomal region leading to predisposition for the development of RA."} {"id": "PMID:1262463", "title": "Fate of soluble carbohydrate in the colon of rats and man.", "content": "The fate of glucose in the colon of rats and man was investigated by measuring breath 14CO2 and fecal 14C after direct instillation of 14C-labeled glucose, acetate, and lactate into the cecum. For the 6 h after administration of as much as 400 mg of [U-14C]-glucose to the rat and 12.5 g to man, 14CO2 excretion was as rapid after intracecal as after intragastric instillation. Less than 20% of 14C instilled into the cecum as glucose was recovered in feces and only about 15% of this fecal 14C was in a dialyzable form. The conversion of intracecally administered glucose to CO2 was dependent upon the presence of the colonic flora, as evidenced by the minimal excretion of 14CO2 after administration of [14C]glucose to germ-free rats. In contrast, acetate and lactate, fermentation products of glucose, were converted to CO2 as rapidly in germ-free rats as in their conventional counterparts. Measurement of O2 availability in the colonic lumen indicated that insufficient O2 was available for the aerobic metabolism of glucose by the colonic bacteria. These experiments suggest that the colon bacteria anaerobically metabolize most of the glucose to short-chain fatty acids, which are absorbed and oxidized by the host. Most of the remaining fecal glucose is converted to a larger molecular form that has limited osmotic activity. Thus, the colonic flora benefits the host by reducing the osmotic load of nonabsorbed carbohydrate and by making possible the salvage of a large percentage of the calories of carbohydrate, which is not absorbed in the small bowel.", "contents": "Fate of soluble carbohydrate in the colon of rats and man. The fate of glucose in the colon of rats and man was investigated by measuring breath 14CO2 and fecal 14C after direct instillation of 14C-labeled glucose, acetate, and lactate into the cecum. For the 6 h after administration of as much as 400 mg of [U-14C]-glucose to the rat and 12.5 g to man, 14CO2 excretion was as rapid after intracecal as after intragastric instillation. Less than 20% of 14C instilled into the cecum as glucose was recovered in feces and only about 15% of this fecal 14C was in a dialyzable form. The conversion of intracecally administered glucose to CO2 was dependent upon the presence of the colonic flora, as evidenced by the minimal excretion of 14CO2 after administration of [14C]glucose to germ-free rats. In contrast, acetate and lactate, fermentation products of glucose, were converted to CO2 as rapidly in germ-free rats as in their conventional counterparts. Measurement of O2 availability in the colonic lumen indicated that insufficient O2 was available for the aerobic metabolism of glucose by the colonic bacteria. These experiments suggest that the colon bacteria anaerobically metabolize most of the glucose to short-chain fatty acids, which are absorbed and oxidized by the host. Most of the remaining fecal glucose is converted to a larger molecular form that has limited osmotic activity. Thus, the colonic flora benefits the host by reducing the osmotic load of nonabsorbed carbohydrate and by making possible the salvage of a large percentage of the calories of carbohydrate, which is not absorbed in the small bowel."} {"id": "PMID:1262464", "title": "Membrane permeability as a cause of transport defects in experimental Fanconi syndrome. A new hypothesis.", "content": "The injection of sodium maleate (200-400 mg/kg) into rats produces aminoaciduria along with glycosuria and phosphaturia, resembling the Fanconi syndrome. This experimental model was studied by means of microinjections into proximal convoluted tubules of the kidney, stop-flow diuresis, and microperfusion of single nephrons. Our results show that, in maleate-treated rats, competition between amino acids or related structures (L-proline, L-OH-proline, and glycine) possesses the same characteristics, and net influx of amino acids appear normal at the proximal nephron. Data obtained by classical stop-flow techniques and single nephron microperfusions also indicate a normal entry of labeled amino acids (L-lysine, glycine, L-valine, L-proline, L-cystine), and 3-0-methyl-D-[3H]glucose and [32P]phosphate from the luminal side of the proximal tubule cell. However, the efflux of molecules from the cell appears enhanced throughout the proximal and distal tubule; molecules that exit at this site are excreted directly into the urine. Our results suggest that the phosphaturia, aminoaciduria, and glycosuria of the experimental Fanconi syndrome can be explained by a modification of the cell membrane permeability (increased efflux) at distal sites of the nephron rather than by a modification of the membrane transport (decreased influx) at the proximal sites, as is currently accepted. Our data also stress the importance of efflux phenomena in membrane transport.", "contents": "Membrane permeability as a cause of transport defects in experimental Fanconi syndrome. A new hypothesis. The injection of sodium maleate (200-400 mg/kg) into rats produces aminoaciduria along with glycosuria and phosphaturia, resembling the Fanconi syndrome. This experimental model was studied by means of microinjections into proximal convoluted tubules of the kidney, stop-flow diuresis, and microperfusion of single nephrons. Our results show that, in maleate-treated rats, competition between amino acids or related structures (L-proline, L-OH-proline, and glycine) possesses the same characteristics, and net influx of amino acids appear normal at the proximal nephron. Data obtained by classical stop-flow techniques and single nephron microperfusions also indicate a normal entry of labeled amino acids (L-lysine, glycine, L-valine, L-proline, L-cystine), and 3-0-methyl-D-[3H]glucose and [32P]phosphate from the luminal side of the proximal tubule cell. However, the efflux of molecules from the cell appears enhanced throughout the proximal and distal tubule; molecules that exit at this site are excreted directly into the urine. Our results suggest that the phosphaturia, aminoaciduria, and glycosuria of the experimental Fanconi syndrome can be explained by a modification of the cell membrane permeability (increased efflux) at distal sites of the nephron rather than by a modification of the membrane transport (decreased influx) at the proximal sites, as is currently accepted. Our data also stress the importance of efflux phenomena in membrane transport."} {"id": "PMID:1262465", "title": "Adrenergic regulation of blood pressure in chronic renal failure.", "content": "Previous investigations have suggested that significant hypotension during hemodialysis may result from abnormalities of sympathetic nervous system activity. To further evaluate these phenomena, plasma dopamine beta-hydroxylase (D beta H) and cold pressor test (proposed indexes of efferent sympathetic nervous system activity) and amyl nitrite inhalation (an index of the entire baroreceptor reflex arc) were studied in two groups of patients: group I, patients exhibiting a mean arterial pressure decrease to less than 70 mm Hg during less than 10% of dialyses; group II (hemodialysis hypotension), patients with a mean arterial pressure decrease to less than 70 mm Hg during more than 90% of dialyses. The groups were similar with respect to plasma renin activity, renin response to ultrafiltration, age, duration of dialysis, nerve conduction velocity, plasma protein concentration, hematocrit, dialysis weight change, resting heart rate, sex, race, blood pressure and heart rate response to cold pressor test, and 125I-albumin plasma volume. Supine mean arterial pressure was higher in patients with hemodialysis hypotension than in patients without hemodialysis hypotension (group I) both before and after dialysis. Plasma D beta H activity was significantly higher in patients with hemodialysis hypotension (group II) than in group I both before and after dialysis. Amyl nitrite inhalation, expressed as change in delta R-R interval/mean arterial pressure decrease, was less in hemodialysis hypotension patients. These results suggest that hemodialysis hypotension may result from a lesion in the baroreceptors, cardiopulmonary receptors, or visceral afferent nerves. Furthermore, elevated mean arterial pressure in patients with hemodialysis hypotension may be neurogenic in origin, as reflected by plasma D beta H activity, and appears similar to the hypertension that follows baroreceptor deafferentation of experimental animals.", "contents": "Adrenergic regulation of blood pressure in chronic renal failure. Previous investigations have suggested that significant hypotension during hemodialysis may result from abnormalities of sympathetic nervous system activity. To further evaluate these phenomena, plasma dopamine beta-hydroxylase (D beta H) and cold pressor test (proposed indexes of efferent sympathetic nervous system activity) and amyl nitrite inhalation (an index of the entire baroreceptor reflex arc) were studied in two groups of patients: group I, patients exhibiting a mean arterial pressure decrease to less than 70 mm Hg during less than 10% of dialyses; group II (hemodialysis hypotension), patients with a mean arterial pressure decrease to less than 70 mm Hg during more than 90% of dialyses. The groups were similar with respect to plasma renin activity, renin response to ultrafiltration, age, duration of dialysis, nerve conduction velocity, plasma protein concentration, hematocrit, dialysis weight change, resting heart rate, sex, race, blood pressure and heart rate response to cold pressor test, and 125I-albumin plasma volume. Supine mean arterial pressure was higher in patients with hemodialysis hypotension than in patients without hemodialysis hypotension (group I) both before and after dialysis. Plasma D beta H activity was significantly higher in patients with hemodialysis hypotension (group II) than in group I both before and after dialysis. Amyl nitrite inhalation, expressed as change in delta R-R interval/mean arterial pressure decrease, was less in hemodialysis hypotension patients. These results suggest that hemodialysis hypotension may result from a lesion in the baroreceptors, cardiopulmonary receptors, or visceral afferent nerves. Furthermore, elevated mean arterial pressure in patients with hemodialysis hypotension may be neurogenic in origin, as reflected by plasma D beta H activity, and appears similar to the hypertension that follows baroreceptor deafferentation of experimental animals."} {"id": "PMID:1262466", "title": "Degradation of circulating DNA by extracorporeal circulation over nuclease immobilized on nylon microcapsules.", "content": "Studies were undertaken to determine whether deoxyribonuclease I, (DNase I) once immobilized on activated nylon microspheres, would be capable of degrading circulating DNA in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 4.73 mg of Dnase I. In vitro studies showed that DNase I immobilized on microspheres degreded a significant percentage of 125I-native DNA (nDNA) within 15 min. Mongrel dogs were injected with 125I-nDNA and a variation in initial t 1/2 in individual animals was observed. Therefore, for experimental studies, 125I-nDNA was injected and decay was recorded during a control period in which untreated microcapsules were utilized in the extracorporeal system. DNase I microspheres were then introduced into the extracorporeal circuit which resulted in an acceleration of degradation of acid precipitable 125I-nDNA. When 200 mug of unlabeled DNA with 125I-nDNA was injected, a similar augmentation of DNA degradation was noted after extracorporeal circulation over DNase I microcapsules. This effect could not be attributed to release of DNase I from the microspheres since no 131I-DNase was detected in the serum or organs of the dogs at the conclusion of the experiments. 125I-nDNA:anti-DNA complexes were passively injected into dogs and after a similar control period of circulation over untreated microcapsules. DNase I microspheres were introduced. Results showed a rapid acceleration in the degradation rate of 125I-nDNA:anti-DNA complexes precipitable with (NH4)2SO4. Extracorporeal circulation over nylon microspheres resulted in no significant alteration of the host's hematocrit or platelet count, and little residual cellular debris on the microcapsules. These data suggest that DNAase immobilized on nylon microspheres may have a potential role in the specific therapy of systemic lupus erythematosus, when it is desirable to hydrolyze DNA circulating free or in combination with antibody.", "contents": "Degradation of circulating DNA by extracorporeal circulation over nuclease immobilized on nylon microcapsules. Studies were undertaken to determine whether deoxyribonuclease I, (DNase I) once immobilized on activated nylon microspheres, would be capable of degrading circulating DNA in vitro and in vivo in an extracorporeal circulation system in dogs. Nylon microspheres were prepared and after gentle hydrolysis and glutaraldehyde treatment, demonstrated a retention of up to 4.73 mg of Dnase I. In vitro studies showed that DNase I immobilized on microspheres degreded a significant percentage of 125I-native DNA (nDNA) within 15 min. Mongrel dogs were injected with 125I-nDNA and a variation in initial t 1/2 in individual animals was observed. Therefore, for experimental studies, 125I-nDNA was injected and decay was recorded during a control period in which untreated microcapsules were utilized in the extracorporeal system. DNase I microspheres were then introduced into the extracorporeal circuit which resulted in an acceleration of degradation of acid precipitable 125I-nDNA. When 200 mug of unlabeled DNA with 125I-nDNA was injected, a similar augmentation of DNA degradation was noted after extracorporeal circulation over DNase I microcapsules. This effect could not be attributed to release of DNase I from the microspheres since no 131I-DNase was detected in the serum or organs of the dogs at the conclusion of the experiments. 125I-nDNA:anti-DNA complexes were passively injected into dogs and after a similar control period of circulation over untreated microcapsules. DNase I microspheres were introduced. Results showed a rapid acceleration in the degradation rate of 125I-nDNA:anti-DNA complexes precipitable with (NH4)2SO4. Extracorporeal circulation over nylon microspheres resulted in no significant alteration of the host's hematocrit or platelet count, and little residual cellular debris on the microcapsules. These data suggest that DNAase immobilized on nylon microspheres may have a potential role in the specific therapy of systemic lupus erythematosus, when it is desirable to hydrolyze DNA circulating free or in combination with antibody."} {"id": "PMID:1262467", "title": "The effect of hepatectomy on the synthesis of 25-hydroxyvitamin D3.", "content": "The metabolism of [3H]vitamin D3 in hepatectomized vitamin D-deficient rats has been studied. Hepatectomy drastically disrupts vitamin D3 metabolism as revealed by prolonged high levels of [3H] vitamin D3 in the plasma compartment even 12 h after dose in contrast to sham-operated controls. Some conversion of [3H] vitamin D3 to [3H]25-hydroxyvitamin D3 was detected in hepatectomized rats, but the amount was small in spite of the high circulating levels of [3H]vitamin D3. Since the liver initially takes up much of an administered dose in normal animals and the conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 is small in hepatectomized rats in spite of high circulating [3H]-vitamin D3, it is concluded that the liver plays a major role in the metabolism of vitamin D3 to 25-hydroxy-vitamin D3.", "contents": "The effect of hepatectomy on the synthesis of 25-hydroxyvitamin D3. The metabolism of [3H]vitamin D3 in hepatectomized vitamin D-deficient rats has been studied. Hepatectomy drastically disrupts vitamin D3 metabolism as revealed by prolonged high levels of [3H] vitamin D3 in the plasma compartment even 12 h after dose in contrast to sham-operated controls. Some conversion of [3H] vitamin D3 to [3H]25-hydroxyvitamin D3 was detected in hepatectomized rats, but the amount was small in spite of the high circulating levels of [3H]vitamin D3. Since the liver initially takes up much of an administered dose in normal animals and the conversion of [3H]vitamin D3 to [3H]25-hydroxyvitamin D3 is small in hepatectomized rats in spite of high circulating [3H]-vitamin D3, it is concluded that the liver plays a major role in the metabolism of vitamin D3 to 25-hydroxy-vitamin D3."} {"id": "PMID:1262468", "title": "Location of phosphatidylethanolamine and phosphatidylserine in the human platelet plasma membrane.", "content": "The location of phospholipids in the human platelet plasma membrane was probed with 2, 4, 6-trinitrobenzenesulfonate (TNBS). TNBS does not penetrate inintact cells and can label phosphatidylethanolamine (PE) and phosphatidylserine (PS). In tact platelets, PE is not accessible to TNBS during the initial 15 min. However, 6.9% PE reacts with TNBS after 30 min and 17.9% PE is labeled after 90 min. In intact platelets, PS is not labeled even after 2 h. In contrast, in phospholipids extracted from platelets 71% PE and 26.5% PS react with TNBS within 5 min. This indicates that PS is inaccessible and PE is relatively inaccessible to TNBS in intact platelets. After incubation of platelets with thrombin, there is increased labeling of PE but no labeling of PS. The incubation of platelets with thrombin (0.05 U/ml) for 5 min results in 16.2% increase of PE labeling during subsequent 30-min incubation with TNBS. PS does not appear to be a component of the functional surface of platelets. However, exposure of PE may have a critical role in platelet hemostatic function. The implication of the study is that there is asymmetry of phopholipids in the platelet plasma membrane which has considerable physiological significance.", "contents": "Location of phosphatidylethanolamine and phosphatidylserine in the human platelet plasma membrane. The location of phospholipids in the human platelet plasma membrane was probed with 2, 4, 6-trinitrobenzenesulfonate (TNBS). TNBS does not penetrate inintact cells and can label phosphatidylethanolamine (PE) and phosphatidylserine (PS). In tact platelets, PE is not accessible to TNBS during the initial 15 min. However, 6.9% PE reacts with TNBS after 30 min and 17.9% PE is labeled after 90 min. In intact platelets, PS is not labeled even after 2 h. In contrast, in phospholipids extracted from platelets 71% PE and 26.5% PS react with TNBS within 5 min. This indicates that PS is inaccessible and PE is relatively inaccessible to TNBS in intact platelets. After incubation of platelets with thrombin, there is increased labeling of PE but no labeling of PS. The incubation of platelets with thrombin (0.05 U/ml) for 5 min results in 16.2% increase of PE labeling during subsequent 30-min incubation with TNBS. PS does not appear to be a component of the functional surface of platelets. However, exposure of PE may have a critical role in platelet hemostatic function. The implication of the study is that there is asymmetry of phopholipids in the platelet plasma membrane which has considerable physiological significance."} {"id": "PMID:1262469", "title": "Correction of characteristic abnormalities of microtubule function and granule morphology in Chediak-Higashi syndrome with cholinergic agonists.", "content": "Chediak-Higashi (CH) syndrome is a genetic disorder of children and certain animal species including the beige mouse. We have previously described a membrane abnormality in CH mouse polymorphonuclear leukocytes (PMH). Whereas normal mouse PMN do not form surface caps with concanavalin A except after treatment with agents such as colchicine that inhibit microtubule assembly, CH mouse PMN show spontaneous cap formation. This capping is inhibited by 3',5 cyclic guanosine monophosphate and by the cholinergic agonists carbamylcholine and carbamyl beta-methylcholine that increase 3',5' cyclic guanosine monophosphate generation. These data suggested that microtubule function may be impaired in CH syndrome perhaps secondary to an abnormality in 3',5' cyclic guanosine monophosphate generation. The cholinergic agonists were also shown to prevent development of the giant granules that are pathognomonic of CH syndrome in embryonic fibroblasts isolated from CH mice and cultured in vitro. In this report it is shown that an extreme degree of spontaneous concanavalin A cap formation is also characteristic of peripheral blood PMN from two patients with CH syndrome. This indicates an abnormality of microtubule function in CH syndrome in man. 3',5' cyclic guanosine monophasphate, carbamylcholine, and carbamyl beta-methylcholine reduce spontaneous capping in CH cells. In addition, it is shown that monocytes isolated from the patients' blood and incubated in tissue culture generate a large complement of abnormal granules. When the same cells mature in vitro in the presence of carbamylcholine or carbamyl beta-methylcholine, the proportion of cells containing morphologically normal granules is significantly increased. These responses can be reproduced in vivo in the beige (CH) mouse. Animals treated for 3 wk and longer with carbamylcholine or carbamyl beta-methylcholline show normal granule morphology and a normal degree of concanavalin A cap formation in peripheral blood PMN leukocytes.", "contents": "Correction of characteristic abnormalities of microtubule function and granule morphology in Chediak-Higashi syndrome with cholinergic agonists. Chediak-Higashi (CH) syndrome is a genetic disorder of children and certain animal species including the beige mouse. We have previously described a membrane abnormality in CH mouse polymorphonuclear leukocytes (PMH). Whereas normal mouse PMN do not form surface caps with concanavalin A except after treatment with agents such as colchicine that inhibit microtubule assembly, CH mouse PMN show spontaneous cap formation. This capping is inhibited by 3',5 cyclic guanosine monophosphate and by the cholinergic agonists carbamylcholine and carbamyl beta-methylcholine that increase 3',5' cyclic guanosine monophosphate generation. These data suggested that microtubule function may be impaired in CH syndrome perhaps secondary to an abnormality in 3',5' cyclic guanosine monophosphate generation. The cholinergic agonists were also shown to prevent development of the giant granules that are pathognomonic of CH syndrome in embryonic fibroblasts isolated from CH mice and cultured in vitro. In this report it is shown that an extreme degree of spontaneous concanavalin A cap formation is also characteristic of peripheral blood PMN from two patients with CH syndrome. This indicates an abnormality of microtubule function in CH syndrome in man. 3',5' cyclic guanosine monophasphate, carbamylcholine, and carbamyl beta-methylcholine reduce spontaneous capping in CH cells. In addition, it is shown that monocytes isolated from the patients' blood and incubated in tissue culture generate a large complement of abnormal granules. When the same cells mature in vitro in the presence of carbamylcholine or carbamyl beta-methylcholine, the proportion of cells containing morphologically normal granules is significantly increased. These responses can be reproduced in vivo in the beige (CH) mouse. Animals treated for 3 wk and longer with carbamylcholine or carbamyl beta-methylcholline show normal granule morphology and a normal degree of concanavalin A cap formation in peripheral blood PMN leukocytes."} {"id": "PMID:1262470", "title": "Effects of isoproterenol on regional myocardial function, electrogram, and blood flow in conscious dogs with myocardial ischemia.", "content": "The effects of coronary occlusion and of subsequent isoproterenol infusion were examined in conscious dogs. Left ventricular (LV) function was assessed by measurements of LV diameter, pressure, velocity and dP/dt/P, and regional myocardial function was assessed by measurements of segment length (SL) and velocity of SL shortening in normal, border, and ischemic zones. Regional myocardial function was measured from the same sites, along with intramyocardial electrograms and regional myocardial blood flow as determined by radioactive microspheres. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reductions and graded increases in ST segment elevation. Isoproterenol improved overall LV function, and function in the normal zone. Isoproterenol also improved function in 19 of 21 border-zone segments and in all moderately ischemic segments, while elevating further the ST segments. These changes were accompanied by increases in myocardial blood flow. In contrast, in severely ischemic segments, isoproterenol resulted in a deterioration of function, in that paradoxical motion occurred in segments previously akinetic during systole, while paradoxical motion was intensified in those segments in which it was already present. These changes were accompanied by further ST segment elevation but not by concurrent increases in blood flow. In addition, in 2 of 21 border zone segments, myocardial blood flow fell and these segments responded to isoproterenol with complete loss of function; paradoxical motion developed. Thus, in the conscious dog, a strong inotropic agent can improve function, even in the ischemic myocardium, as long as the required additional blood flow can be provided wither through primary or collateral channels.", "contents": "Effects of isoproterenol on regional myocardial function, electrogram, and blood flow in conscious dogs with myocardial ischemia. The effects of coronary occlusion and of subsequent isoproterenol infusion were examined in conscious dogs. Left ventricular (LV) function was assessed by measurements of LV diameter, pressure, velocity and dP/dt/P, and regional myocardial function was assessed by measurements of segment length (SL) and velocity of SL shortening in normal, border, and ischemic zones. Regional myocardial function was measured from the same sites, along with intramyocardial electrograms and regional myocardial blood flow as determined by radioactive microspheres. Coronary occlusion resulted in graded loss of function from the normal to severely ischemic zones with graded flow reductions and graded increases in ST segment elevation. Isoproterenol improved overall LV function, and function in the normal zone. Isoproterenol also improved function in 19 of 21 border-zone segments and in all moderately ischemic segments, while elevating further the ST segments. These changes were accompanied by increases in myocardial blood flow. In contrast, in severely ischemic segments, isoproterenol resulted in a deterioration of function, in that paradoxical motion occurred in segments previously akinetic during systole, while paradoxical motion was intensified in those segments in which it was already present. These changes were accompanied by further ST segment elevation but not by concurrent increases in blood flow. In addition, in 2 of 21 border zone segments, myocardial blood flow fell and these segments responded to isoproterenol with complete loss of function; paradoxical motion developed. Thus, in the conscious dog, a strong inotropic agent can improve function, even in the ischemic myocardium, as long as the required additional blood flow can be provided wither through primary or collateral channels."} {"id": "PMID:1262471", "title": "Permselectivity of of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using neutral dextran.", "content": "Polydisperse [3h] dextran was infused into eight Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN), thereby permitting direct measurements of pressures and flows in surface glomeruli and fractional clearances for dextrans [(U/P) dextran/(U/P) inulin] ranging in radius from 18 to 42 A. Despite glomerular injury, evidenced morphologically and by a marked reduction in the glomerular capillary ultrafiltration coefficient, the glomerular filtration rate remained normal because of a compensating increase in the mean net ultrafiltration pressure. In NSN rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and dextrans were shown to be neither secreted nor reabsorbed. For dextran radii of 18, 22, 26, 30, 34, 38, and 42 A, (U/P) dextran/(U/P) inulin in NSN and control rats, respectively, averaged 0.90 vs. 0.99, 0.81 vs. 0.97, 0.63 vs. 0.83, 0.38 vs 0.55, 0.20 vs. 0.30, 0.08 vs. 0.11, and 0.02 vs. 0.03. Using a theory based on macromolecular transport through pores, the results indicate that in NSN rats, effective pore radius is the same as in controls, approximately 50 A. In NSN, however, the ratio of total pore surface area to pore length, a measure of the number of pores, is reduced to approximately 1/3 that of control, probably due to a reduction in capillary surface area. These results suggest that proteinuria in glomerular disease is not due simply to increases in effective pore radius or number of pores, as previously believed. Using a second theoretical approach, based on the Kedem-Katchalsky flux equations, dextran permeability across glomerular capillaries was found to be slightly lower, and reflection coefficient slightly higher in NSN than in control rats.", "contents": "Permselectivity of of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using neutral dextran. Polydisperse [3h] dextran was infused into eight Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN), thereby permitting direct measurements of pressures and flows in surface glomeruli and fractional clearances for dextrans [(U/P) dextran/(U/P) inulin] ranging in radius from 18 to 42 A. Despite glomerular injury, evidenced morphologically and by a marked reduction in the glomerular capillary ultrafiltration coefficient, the glomerular filtration rate remained normal because of a compensating increase in the mean net ultrafiltration pressure. In NSN rats, as in normal controls, inulin was found to permeate the glomerular capillary wall without measurable restriction, and dextrans were shown to be neither secreted nor reabsorbed. For dextran radii of 18, 22, 26, 30, 34, 38, and 42 A, (U/P) dextran/(U/P) inulin in NSN and control rats, respectively, averaged 0.90 vs. 0.99, 0.81 vs. 0.97, 0.63 vs. 0.83, 0.38 vs 0.55, 0.20 vs. 0.30, 0.08 vs. 0.11, and 0.02 vs. 0.03. Using a theory based on macromolecular transport through pores, the results indicate that in NSN rats, effective pore radius is the same as in controls, approximately 50 A. In NSN, however, the ratio of total pore surface area to pore length, a measure of the number of pores, is reduced to approximately 1/3 that of control, probably due to a reduction in capillary surface area. These results suggest that proteinuria in glomerular disease is not due simply to increases in effective pore radius or number of pores, as previously believed. Using a second theoretical approach, based on the Kedem-Katchalsky flux equations, dextran permeability across glomerular capillaries was found to be slightly lower, and reflection coefficient slightly higher in NSN than in control rats."} {"id": "PMID:1262472", "title": "Permselectivity of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using dextran sulfate.", "content": "To determine whether the increased filtration of serum proteins after glomerular injury is the consequence of altered electrostatic properties of the glomerular capillary wall, we measured fractional clearances of the anionic polymer, dextran sulfate, in nine Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). In agreement with previous studied from this laboratory, whole kidney and single nephron glomerular filtration rates were normal in NSN rats despite histological evidence of glomerular injury, and despite a marked reduction in the glomerular capillary ultrafiltration coefficient to approximately one-third of normal. In the companion study (9), it was shown that in NSN rats the mean fractional clearances of neutral dextrans over the range of effective molecular radii from 18 to 42 A were reduced, compared to normla. In contrast, in the present study the mean fractional clearances for dextran sulfate over the same range of molecular radii were significantly greater than those found previously for normal Munich-Wistar rats. The fractional clearance of dextran sulfate molecules of the same molecular radius as serum albumin (approximately 36 A) was increased markedly, from 0.015 +/- 0.005 (SEM) in nonnephritic controls to 0.24 +/- 0.03 in NSN (P less than 0.001). The sialoprotein content of glomeruli, estimated by the colloidal iron reaction, was reduced in NSN rats as compared to normal controls. It is concluded that the abnormal filtration of anionic serum proteins, such as albumin, seen in glomerulopathies is, at least in part, the consequence of loss of fixed negative charges from the glomerular capillary wall.", "contents": "Permselectivity of the glomerular capillary wall. Studies of experimental glomerulonephritis in the rat using dextran sulfate. To determine whether the increased filtration of serum proteins after glomerular injury is the consequence of altered electrostatic properties of the glomerular capillary wall, we measured fractional clearances of the anionic polymer, dextran sulfate, in nine Munich-Wistar rats in the early autologous phase of nephrotoxic serum nephritis (NSN). In agreement with previous studied from this laboratory, whole kidney and single nephron glomerular filtration rates were normal in NSN rats despite histological evidence of glomerular injury, and despite a marked reduction in the glomerular capillary ultrafiltration coefficient to approximately one-third of normal. In the companion study (9), it was shown that in NSN rats the mean fractional clearances of neutral dextrans over the range of effective molecular radii from 18 to 42 A were reduced, compared to normla. In contrast, in the present study the mean fractional clearances for dextran sulfate over the same range of molecular radii were significantly greater than those found previously for normal Munich-Wistar rats. The fractional clearance of dextran sulfate molecules of the same molecular radius as serum albumin (approximately 36 A) was increased markedly, from 0.015 +/- 0.005 (SEM) in nonnephritic controls to 0.24 +/- 0.03 in NSN (P less than 0.001). The sialoprotein content of glomeruli, estimated by the colloidal iron reaction, was reduced in NSN rats as compared to normal controls. It is concluded that the abnormal filtration of anionic serum proteins, such as albumin, seen in glomerulopathies is, at least in part, the consequence of loss of fixed negative charges from the glomerular capillary wall."} {"id": "PMID:1262473", "title": "Spectrofluorescent detection of in vivo red cell lipid peroxidation in patients treated with diaminodiphenylsulfone.", "content": "In the absence of vitamin E deficiency, red cell lipid peroxidation has not been clearly demonstrated in freshly drawn blood obtained from patients with various hemolytic anemias despite indirect evidence that oxidative decomposition of cell membrane unsaturated fatty acids occurs in these particular hemolytic states. Recent studies have indicated that malonaldehyde, a decomposition product of oxidized polyunsaturated fatty acids, is able to covalently cross-link the amino groups of protein or lipid resulting in a fluorescent compound. In the present study we have utilized spectrofluorescent technique to assess whether such fluorescence is present in red cell lipid extracts in association with lipid peroxidation. In vitro red cell lipid peroxidation produced by ultraviolet radiation or the oxidant gas ozone was associated with the development of a fluorescent peak (excitation maximum 360 nm; emission maximum 440 nm) in lipid-containing red cell extracts Similar fluorescence was observed after incubation of red cells with malonaldehyde or with malonaldehyde-containing extracts of peroxidized red cell lipid. Spectrofluorescent evaluation of chloroform: isopropanol extracts obtained from the freshly drawn red cells of six patients receiving the oxidant hemolytic drug diaminodiphenylsulfone also revealed a peak at 440 nm which ranged from 39 to 78 U. In contrast, the levels in samples obtained from 11 hematologically normal subjects were 17-27 fluorescence U. No evidence for an increase in blood levels of free malomaldehyde was observed using the 2-thiobarbituric acid test which is the most commonly performed assay of lipid peroxidation. Serum vitamin E levels were within the normal range. Density separation indicated that the bulk of the fluorescence was present in older red cells. A similar fluorescent peak was also observed in lipid-containing extracts of red cells obtained from rabbits repeatedly injected with phenylhydrazine. The finding of fluorescent spectra consistent with the cross-linking of aminolid by malonaldehyde in the red cells of patients receiving diaminodiphenylsulfone indicates that in vivo red cell lipid peroxidation does occur in the absence of vitamin E deficiency.", "contents": "Spectrofluorescent detection of in vivo red cell lipid peroxidation in patients treated with diaminodiphenylsulfone. In the absence of vitamin E deficiency, red cell lipid peroxidation has not been clearly demonstrated in freshly drawn blood obtained from patients with various hemolytic anemias despite indirect evidence that oxidative decomposition of cell membrane unsaturated fatty acids occurs in these particular hemolytic states. Recent studies have indicated that malonaldehyde, a decomposition product of oxidized polyunsaturated fatty acids, is able to covalently cross-link the amino groups of protein or lipid resulting in a fluorescent compound. In the present study we have utilized spectrofluorescent technique to assess whether such fluorescence is present in red cell lipid extracts in association with lipid peroxidation. In vitro red cell lipid peroxidation produced by ultraviolet radiation or the oxidant gas ozone was associated with the development of a fluorescent peak (excitation maximum 360 nm; emission maximum 440 nm) in lipid-containing red cell extracts Similar fluorescence was observed after incubation of red cells with malonaldehyde or with malonaldehyde-containing extracts of peroxidized red cell lipid. Spectrofluorescent evaluation of chloroform: isopropanol extracts obtained from the freshly drawn red cells of six patients receiving the oxidant hemolytic drug diaminodiphenylsulfone also revealed a peak at 440 nm which ranged from 39 to 78 U. In contrast, the levels in samples obtained from 11 hematologically normal subjects were 17-27 fluorescence U. No evidence for an increase in blood levels of free malomaldehyde was observed using the 2-thiobarbituric acid test which is the most commonly performed assay of lipid peroxidation. Serum vitamin E levels were within the normal range. Density separation indicated that the bulk of the fluorescence was present in older red cells. A similar fluorescent peak was also observed in lipid-containing extracts of red cells obtained from rabbits repeatedly injected with phenylhydrazine. The finding of fluorescent spectra consistent with the cross-linking of aminolid by malonaldehyde in the red cells of patients receiving diaminodiphenylsulfone indicates that in vivo red cell lipid peroxidation does occur in the absence of vitamin E deficiency."} {"id": "PMID:1262474", "title": "Detection of anti-DNA antibody using synthetic antigens. Characterization and clinical significance of binding of poly (deoxyadenylate-deoxythymidylate) by serum.", "content": "Virtually all preparations of DNA used to detect antibody to native DNA (nDNA) by binding assays have been found to be subtly contaminated by single stranded DNA. Because recent DNA binding data have directly challenged the unique role previously attributed to these antibodies in systemic lupus erythematosus (SLE), resolution of the consequent ambiguity is of theoretical and practical importance. It is proposed that a synthetic nDNA molecule (dAT) might circumvent this difficulty by being antigenically equivalent to nDNA while, on theoretical grounds, lacking significant contamination with single stranded DNA or other cellular antigens. These expectations were generally confirmed by biochemical and immunological analyses. In clinical studies, sera from 124 pateints with SLE and from controls were examined for their ability to bind dAT. In contrast to results with KB binding, patients with non-SLE rheumatologic disorders were indistinguishable from normals by dAT binding. dAT binding was elevated in 85% of sera from SLE patients with clinically-judged active nephritis but in only 9% of those with inactive renal disease. Active non-renal disease, including cerebritis, was not associated with increased dAT binding. Individual non-lupus sera which bound increased amounts of KB DNA, failed to bind dAT. It is suggested that such binding resulted from contaminating non-nDNA antigens. When elevated, dAT binding, like KB binding, varied with disease activity and might thus be useful as a parameter thereof. In several patients elevated dAT binding led to the finding, on biopsy, of clinically silent, active, diffuse proliferative nephritis. It is concluded that use of synthetic nDNA antigens such as dAT may offer theoretical and practical advantages over naturally-derived preparations in detecting anti-nDNA, both clinically and for investigational purposes. Also, caution is urged in interpreting DNA binding data derived from incompletely characterized systems, particularly with regard to the occurrence of anti-nDNA antibodies in serum.", "contents": "Detection of anti-DNA antibody using synthetic antigens. Characterization and clinical significance of binding of poly (deoxyadenylate-deoxythymidylate) by serum. Virtually all preparations of DNA used to detect antibody to native DNA (nDNA) by binding assays have been found to be subtly contaminated by single stranded DNA. Because recent DNA binding data have directly challenged the unique role previously attributed to these antibodies in systemic lupus erythematosus (SLE), resolution of the consequent ambiguity is of theoretical and practical importance. It is proposed that a synthetic nDNA molecule (dAT) might circumvent this difficulty by being antigenically equivalent to nDNA while, on theoretical grounds, lacking significant contamination with single stranded DNA or other cellular antigens. These expectations were generally confirmed by biochemical and immunological analyses. In clinical studies, sera from 124 pateints with SLE and from controls were examined for their ability to bind dAT. In contrast to results with KB binding, patients with non-SLE rheumatologic disorders were indistinguishable from normals by dAT binding. dAT binding was elevated in 85% of sera from SLE patients with clinically-judged active nephritis but in only 9% of those with inactive renal disease. Active non-renal disease, including cerebritis, was not associated with increased dAT binding. Individual non-lupus sera which bound increased amounts of KB DNA, failed to bind dAT. It is suggested that such binding resulted from contaminating non-nDNA antigens. When elevated, dAT binding, like KB binding, varied with disease activity and might thus be useful as a parameter thereof. In several patients elevated dAT binding led to the finding, on biopsy, of clinically silent, active, diffuse proliferative nephritis. It is concluded that use of synthetic nDNA antigens such as dAT may offer theoretical and practical advantages over naturally-derived preparations in detecting anti-nDNA, both clinically and for investigational purposes. Also, caution is urged in interpreting DNA binding data derived from incompletely characterized systems, particularly with regard to the occurrence of anti-nDNA antibodies in serum."} {"id": "PMID:1262475", "title": "A comparison of the metabolic response to phagocytosis in human granulocytes and monocytes.", "content": "Recent studies indicate that oxygen radicals such as superoxide or singlet oxygen may be important in the functional activity of human granulocytes. We have examined the possible importance of these radicals in the functional capacity of human blood monocytes. Monocytes, like granulocytes, generate chemiluminescence during phagocytosis. Chemiluminescence is impaired 50-90% by superoxide dismutase, an enzyme which enhances the dismutation of superoxide to hydrogen peroxide. These results indicate that superoxide is related to the chemiluminescence generated by monocytes. Superoxide dismutase in a concentration which impaired chemiluminescence also impaired the staphylococcal killing by monocytes. Hexose monophosphate shunt activity and hydrogen peroxide production by granulocytes and monocytes were also evaluated. The oxidation of [1-14C]glucose was used as a measure of hexose monophosphate shunt activity and the oxidation of [14C]formate as an estimation of hydrogen peroxide production. The oxidation of both substrates by monocytes was increased during phagocytosis but, in contrast to results in granulocytes, was not further increased by the addition of superoxide dismutase. These data indicate that superoxide may be important in bactericidal activity of human monocytes. Our results also suggest that the metabolism of oxygen radicals in monocytes and granulocytes may be different.", "contents": "A comparison of the metabolic response to phagocytosis in human granulocytes and monocytes. Recent studies indicate that oxygen radicals such as superoxide or singlet oxygen may be important in the functional activity of human granulocytes. We have examined the possible importance of these radicals in the functional capacity of human blood monocytes. Monocytes, like granulocytes, generate chemiluminescence during phagocytosis. Chemiluminescence is impaired 50-90% by superoxide dismutase, an enzyme which enhances the dismutation of superoxide to hydrogen peroxide. These results indicate that superoxide is related to the chemiluminescence generated by monocytes. Superoxide dismutase in a concentration which impaired chemiluminescence also impaired the staphylococcal killing by monocytes. Hexose monophosphate shunt activity and hydrogen peroxide production by granulocytes and monocytes were also evaluated. The oxidation of [1-14C]glucose was used as a measure of hexose monophosphate shunt activity and the oxidation of [14C]formate as an estimation of hydrogen peroxide production. The oxidation of both substrates by monocytes was increased during phagocytosis but, in contrast to results in granulocytes, was not further increased by the addition of superoxide dismutase. These data indicate that superoxide may be important in bactericidal activity of human monocytes. Our results also suggest that the metabolism of oxygen radicals in monocytes and granulocytes may be different."} {"id": "PMID:1262476", "title": "Local effects of acute cellular injury on regional myocardial blood flow.", "content": "This study was designed to examine local effects of acute cellular injury on regional myocardial blood flow. Studies were carried out in awake dogs chronically prepared with indwelling catheters in the aorta and left atrium and an occluder on the left circumflex coronary artery. Regional myocardial blood flow was measured by using 7-10-mum radioisotope-labeled microspheres after reestablishing inflow to a region subjected to a 2-h complete coronary occlusion. Microspheres were injected 15 s, 15 min, 4 h, and 3 days after reperfusion to assess effects of cell injury at varying intervals after reperfusion. Effects of acute cellular injury on blood flow were assessed by determining the relationship between regional blood flow and the extent of subsequent cellular necrosis measured in multiple tissue samples, weight 1-2 g, from the entire ischemic zone. The extent of cellular necrosis was determined from histological sections of each tissue sample. Prolonged ischemia effected local tissue responses which altered perfusion as a function of the interval after reperfusion and the subsequent extent of myocardial necrosis. Although the net response in each region immediately after reperfusion was vasodilation, the hyperemia in regions which subsequently suffered cellular necrosis was attenuated in direct proportion to the extent of subsequent infarction. Blood flow to acutely injured regions remained equal to, or in excess of, flow to nonischemic regions 15 min after reperfusion, but at 4 h and 3 days after reperfusion, flow was significantly decreased in regions with greater than 50% infarction. Thus, these data indicate that prolonged ischemia initiates tissue responses which progressively reduce myocardial perfusion after reperfusion. These effects on tissue perfusion may result from normal responses to irreversible injury and (or) abnormal responses to reversible and thus, potentially alterable, ischemic injury.", "contents": "Local effects of acute cellular injury on regional myocardial blood flow. This study was designed to examine local effects of acute cellular injury on regional myocardial blood flow. Studies were carried out in awake dogs chronically prepared with indwelling catheters in the aorta and left atrium and an occluder on the left circumflex coronary artery. Regional myocardial blood flow was measured by using 7-10-mum radioisotope-labeled microspheres after reestablishing inflow to a region subjected to a 2-h complete coronary occlusion. Microspheres were injected 15 s, 15 min, 4 h, and 3 days after reperfusion to assess effects of cell injury at varying intervals after reperfusion. Effects of acute cellular injury on blood flow were assessed by determining the relationship between regional blood flow and the extent of subsequent cellular necrosis measured in multiple tissue samples, weight 1-2 g, from the entire ischemic zone. The extent of cellular necrosis was determined from histological sections of each tissue sample. Prolonged ischemia effected local tissue responses which altered perfusion as a function of the interval after reperfusion and the subsequent extent of myocardial necrosis. Although the net response in each region immediately after reperfusion was vasodilation, the hyperemia in regions which subsequently suffered cellular necrosis was attenuated in direct proportion to the extent of subsequent infarction. Blood flow to acutely injured regions remained equal to, or in excess of, flow to nonischemic regions 15 min after reperfusion, but at 4 h and 3 days after reperfusion, flow was significantly decreased in regions with greater than 50% infarction. Thus, these data indicate that prolonged ischemia initiates tissue responses which progressively reduce myocardial perfusion after reperfusion. These effects on tissue perfusion may result from normal responses to irreversible injury and (or) abnormal responses to reversible and thus, potentially alterable, ischemic injury."} {"id": "PMID:1262478", "title": "Behavioral and physiological effects of examiner sex on process and reactive schizophrenics.", "content": "In the physiological (polygraph) data, the sex of the E (ES) interacted with the sex of the patient (PS) or the patient's process-reactive status (PR) in only 1 of 16 analyses. Only in the heart-rate variability data was the ES by PS interaction significant (p less than .001). Sex of the E had an appreciable effect in two of the three measures of associative disturbance. The ES by PS interaction was significant (p less than .025) in the recall measure of instability of though processes, and the same interaction neared significance (p less than .06) in the multiword response measure of associative disturbance. It appears that the sex of the E should be considered in studies that use measures of associative disturbance and perhaps when heart-rate variability measures are used.", "contents": "Behavioral and physiological effects of examiner sex on process and reactive schizophrenics. In the physiological (polygraph) data, the sex of the E (ES) interacted with the sex of the patient (PS) or the patient's process-reactive status (PR) in only 1 of 16 analyses. Only in the heart-rate variability data was the ES by PS interaction significant (p less than .001). Sex of the E had an appreciable effect in two of the three measures of associative disturbance. The ES by PS interaction was significant (p less than .025) in the recall measure of instability of though processes, and the same interaction neared significance (p less than .06) in the multiword response measure of associative disturbance. It appears that the sex of the E should be considered in studies that use measures of associative disturbance and perhaps when heart-rate variability measures are used."} {"id": "PMID:1262479", "title": "Suicidal behavior and childhood onychophagia in hospitalized psychiatric veterans.", "content": "This investigation of adult suicidal behavior and childhood onychophagia among hospitalized psychiatric male veterans suggests that for only personality disorders does childhood non-onychophagia show a significant relationship to adult nonsuicidal behavior. Otherwise, this study indicates that the presence or abscence of childhood onychophagia is not a significant suicidal or nonsuicidal factor among these veterans with a psychotic, neurotic, or personality disorder classification.", "contents": "Suicidal behavior and childhood onychophagia in hospitalized psychiatric veterans. This investigation of adult suicidal behavior and childhood onychophagia among hospitalized psychiatric male veterans suggests that for only personality disorders does childhood non-onychophagia show a significant relationship to adult nonsuicidal behavior. Otherwise, this study indicates that the presence or abscence of childhood onychophagia is not a significant suicidal or nonsuicidal factor among these veterans with a psychotic, neurotic, or personality disorder classification."} {"id": "PMID:1262480", "title": "Emotional and social real-life problem-solving thinking in adolescent and adult psychiatric patients.", "content": "The ability of adult and adolescent psychiatric patients to solve emotional problems such as anxiety and depression as well as problems that arise within the social sphere was examined, as was the question of whether the abilities to solve problems in the emotional and social spheres are related. With IQ partialled out, patients and controls did not differ on emotional problem-solving ability, but did differ on social problem-solving ability. Emotional problem-solving ability was found to be related to intelligence, while social problem-solving ability was not. Emotional problem-solving may require more abstract ability than social problem-solving, and normals may need only social problem-solving for adjustment.", "contents": "Emotional and social real-life problem-solving thinking in adolescent and adult psychiatric patients. The ability of adult and adolescent psychiatric patients to solve emotional problems such as anxiety and depression as well as problems that arise within the social sphere was examined, as was the question of whether the abilities to solve problems in the emotional and social spheres are related. With IQ partialled out, patients and controls did not differ on emotional problem-solving ability, but did differ on social problem-solving ability. Emotional problem-solving ability was found to be related to intelligence, while social problem-solving ability was not. Emotional problem-solving may require more abstract ability than social problem-solving, and normals may need only social problem-solving for adjustment."} {"id": "PMID:1262481", "title": "Androgyny and need achievement in male and female psychiatric inpatients.", "content": "An androgyny (gender identity) and a need achievement (n Ach) test were given to 28 normals, 23 schizophrenic patients, and 23 nonschizophrenic psychiatric patients. The psychiatric groups averaged a little over 3 weeks of hospitalization. There were gender differences for the androgyny and n Ach tests, but there were no significant differences among the three groups and no gender X diagnostic group interactions. There were significant correlations between age and both androgyny and n Ach scores, but no significant correlation between androgyny and n Ach scores.", "contents": "Androgyny and need achievement in male and female psychiatric inpatients. An androgyny (gender identity) and a need achievement (n Ach) test were given to 28 normals, 23 schizophrenic patients, and 23 nonschizophrenic psychiatric patients. The psychiatric groups averaged a little over 3 weeks of hospitalization. There were gender differences for the androgyny and n Ach tests, but there were no significant differences among the three groups and no gender X diagnostic group interactions. There were significant correlations between age and both androgyny and n Ach scores, but no significant correlation between androgyny and n Ach scores."} {"id": "PMID:1262482", "title": "Spatial vs. nonspatial reasoning ability in chronic schizophrenics.", "content": "Forty chronic male VA schizophrenics were matched with veterans who were seeking educational counseling, and both groups were tested on a 32-item measure of spatial and matched nonspatial reasoning questions. Schizophrenics were inferior in spatial reasoning not only when compared to controls, but also when compared to their own level of functioning on nonspatial reasoning, which suggests that spatial reasoning may be selectively more impaired than general reasoning ability in male chronic schizophrenics.", "contents": "Spatial vs. nonspatial reasoning ability in chronic schizophrenics. Forty chronic male VA schizophrenics were matched with veterans who were seeking educational counseling, and both groups were tested on a 32-item measure of spatial and matched nonspatial reasoning questions. Schizophrenics were inferior in spatial reasoning not only when compared to controls, but also when compared to their own level of functioning on nonspatial reasoning, which suggests that spatial reasoning may be selectively more impaired than general reasoning ability in male chronic schizophrenics."} {"id": "PMID:1262483", "title": "Comparison of differential diagnostic discrimination for abbreviated and standard MMPI.", "content": "MMPI response protocols for 194 psychiatric patients were scored on the basis of the first 168 items and then on the usual 400 items. The MMPI-168 raw scores were converted to estimates of conventional clinical scale scores. The Ss were divided into 10 major categories on the basis of final clinical diagnosis. Multiple discriminant analysis was used to compare the discriminant validity of the abbreviated and standard scoring. The results indicated no loss in discrimination to result from scoring based on only the first 168 items. Conversion tables that can be used to transform MMPI-168 raw scores to standard MMPI clinical scale scores are presented for further research and clinical use.", "contents": "Comparison of differential diagnostic discrimination for abbreviated and standard MMPI. MMPI response protocols for 194 psychiatric patients were scored on the basis of the first 168 items and then on the usual 400 items. The MMPI-168 raw scores were converted to estimates of conventional clinical scale scores. The Ss were divided into 10 major categories on the basis of final clinical diagnosis. Multiple discriminant analysis was used to compare the discriminant validity of the abbreviated and standard scoring. The results indicated no loss in discrimination to result from scoring based on only the first 168 items. Conversion tables that can be used to transform MMPI-168 raw scores to standard MMPI clinical scale scores are presented for further research and clinical use."} {"id": "PMID:1262484", "title": "Personality and suicidal history in psychiatric patients.", "content": "The study sample comprised 575 psychiatric referrals for whom MMPI data were available. Patients were categorized according to suicidal history. The attempted suicide and nonsuicidal patients were differentiated significantly on the D, PD, MF, DY, ES, NE, EX, HO, SD, IP, ANX, and UNC scales. Important differences between the sexes emerged; whereas for men the profiles of the suicidal ideation and nonsuicidal patients were similar, for women those of the suicidal ideation and suicide attempt were similar. Male and female suicide attemptors correspond closely in the pattern and degree of deviation from the nonsuicidal patients of their own sex. The study indicates that patients who have a history of suicide attempts constitute a more psychologically disturbed group and points to a need for further examination of the meaning of suicidal ideation for men and women.", "contents": "Personality and suicidal history in psychiatric patients. The study sample comprised 575 psychiatric referrals for whom MMPI data were available. Patients were categorized according to suicidal history. The attempted suicide and nonsuicidal patients were differentiated significantly on the D, PD, MF, DY, ES, NE, EX, HO, SD, IP, ANX, and UNC scales. Important differences between the sexes emerged; whereas for men the profiles of the suicidal ideation and nonsuicidal patients were similar, for women those of the suicidal ideation and suicide attempt were similar. Male and female suicide attemptors correspond closely in the pattern and degree of deviation from the nonsuicidal patients of their own sex. The study indicates that patients who have a history of suicide attempts constitute a more psychologically disturbed group and points to a need for further examination of the meaning of suicidal ideation for men and women."} {"id": "PMID:1262486", "title": "Acceptance of general personality interpretations prior to and after receipt of diagnostic feedback supposedly based on psychological, graphological, and astrological assessment procedures.", "content": "There was no difference in the acceptance of a general personality interpretation supposedly based on psychological, graphological, or astrological assessment procedures. Ss told that their general personality interpretation was based on one of the three assessment procedures, however, accepted the interpretation to a greater degree than did Ss told the interpretation was \"generally true of people.\" S faith in all assessment procedures and perceived diagnostician skill increased significantly from before to after receipt of the diagnostic feedback. Ss elicited a halo response after they had received the interpretation, such that they generated a highly consistent positive (or negative) view of the assessment procedures and diagnostician skills. Implications of results from this acceptance paradigm were discussed for diagnosticians and therapists.", "contents": "Acceptance of general personality interpretations prior to and after receipt of diagnostic feedback supposedly based on psychological, graphological, and astrological assessment procedures. There was no difference in the acceptance of a general personality interpretation supposedly based on psychological, graphological, or astrological assessment procedures. Ss told that their general personality interpretation was based on one of the three assessment procedures, however, accepted the interpretation to a greater degree than did Ss told the interpretation was \"generally true of people.\" S faith in all assessment procedures and perceived diagnostician skill increased significantly from before to after receipt of the diagnostic feedback. Ss elicited a halo response after they had received the interpretation, such that they generated a highly consistent positive (or negative) view of the assessment procedures and diagnostician skills. Implications of results from this acceptance paradigm were discussed for diagnosticians and therapists."} {"id": "PMID:1262485", "title": "Test purpose and test response in psychiatric patients and \"normal\" students.", "content": "The paper reports two experiments concerned with the effects of instructions on personality and self-report symptom measures. The first experiment investigated whether newly referred psychiatric patients respond differently according to whether they believe the questionnaires are being completed for research purposes or as part of a diagnostic procedure. Experiment II examined similar instructional effects with \"normal\" student Ss. Students either were told that the questionnaires were for research purposes or that they were part of a psychiatric screening procedure. Results showed that females in both groups reported more symptoms and had higher neuroticism scores than males. Instructions had no significant effect. It was concluded that such measures may be less sensitive to test-taking bias than often is assumed.", "contents": "Test purpose and test response in psychiatric patients and \"normal\" students. The paper reports two experiments concerned with the effects of instructions on personality and self-report symptom measures. The first experiment investigated whether newly referred psychiatric patients respond differently according to whether they believe the questionnaires are being completed for research purposes or as part of a diagnostic procedure. Experiment II examined similar instructional effects with \"normal\" student Ss. Students either were told that the questionnaires were for research purposes or that they were part of a psychiatric screening procedure. Results showed that females in both groups reported more symptoms and had higher neuroticism scores than males. Instructions had no significant effect. It was concluded that such measures may be less sensitive to test-taking bias than often is assumed."} {"id": "PMID:1262487", "title": "Conformity and modeling in an aversive task.", "content": "High- and low-conformity groups, as measured by the California Personality Inventory, were exposed to a video-taped model who performed an aversive task (i.e., self-administration of electric shock). Comparable groups performed the task without demonstration by the model. In both groups, the modeling procedure produced significantly higher levels of self-administered shock. However, the conformity variable demonstrated no main effect and no interaction with the modeling variable.", "contents": "Conformity and modeling in an aversive task. High- and low-conformity groups, as measured by the California Personality Inventory, were exposed to a video-taped model who performed an aversive task (i.e., self-administration of electric shock). Comparable groups performed the task without demonstration by the model. In both groups, the modeling procedure produced significantly higher levels of self-administered shock. However, the conformity variable demonstrated no main effect and no interaction with the modeling variable."} {"id": "PMID:1262488", "title": "Influence of physical fitness on second- and third-order personality factors using orthogonal and oblique rotations.", "content": "The study investigated the relationship between physical fitness and personality variables at second- and third-order factor-analytic structures. Further, the stability of the factor structures at pre- and post-physical fitness program tests was examined by orthogonal and oblique rotations. Physical fitness and personality data were collected on 56 middle-aged males. The fitness and personality variables were factor analyzed and rotated orthogonally and obliquely by the principal axis form of solution. As a result, five second-order factors were extracted, both initially and finally. Factor scores were estimated for each S on each of the second-order factors, and data were factor analyzed to extract the third-order factors. The second-order factors closely resembled Cattell's factors, but subtle differences were found to exist between initial and final factor structures that may have been due to the influence of the fitness program. Two third-order factors were extracted initially and three finally when the factor scores were rotated orthogonally and obliquely, and physical fitness was associated with two of these hierarchical factors both initially and finally. The hierarchical factor structures appeared to be comparable to the scales of Eysenck. On the basis of the present findings it was concluded that the problem of rotation was not of importance and scientifically uninteresting and that the hierarchical factor solutions were highly stable. Further, it appears that the hierarchical levels of personality are manifested in two syndromes confounded by \"traits\" and \"states\" of personality. These two syndromes are Introversion vs. Extraversion and Neuroticism vs. Stability. The extraction of additional factors, such as Low Superego Strength vs. High Superego Strength, as in this study, is completely dependent upon the treatment or conditions superimposed.", "contents": "Influence of physical fitness on second- and third-order personality factors using orthogonal and oblique rotations. The study investigated the relationship between physical fitness and personality variables at second- and third-order factor-analytic structures. Further, the stability of the factor structures at pre- and post-physical fitness program tests was examined by orthogonal and oblique rotations. Physical fitness and personality data were collected on 56 middle-aged males. The fitness and personality variables were factor analyzed and rotated orthogonally and obliquely by the principal axis form of solution. As a result, five second-order factors were extracted, both initially and finally. Factor scores were estimated for each S on each of the second-order factors, and data were factor analyzed to extract the third-order factors. The second-order factors closely resembled Cattell's factors, but subtle differences were found to exist between initial and final factor structures that may have been due to the influence of the fitness program. Two third-order factors were extracted initially and three finally when the factor scores were rotated orthogonally and obliquely, and physical fitness was associated with two of these hierarchical factors both initially and finally. The hierarchical factor structures appeared to be comparable to the scales of Eysenck. On the basis of the present findings it was concluded that the problem of rotation was not of importance and scientifically uninteresting and that the hierarchical factor solutions were highly stable. Further, it appears that the hierarchical levels of personality are manifested in two syndromes confounded by \"traits\" and \"states\" of personality. These two syndromes are Introversion vs. Extraversion and Neuroticism vs. Stability. The extraction of additional factors, such as Low Superego Strength vs. High Superego Strength, as in this study, is completely dependent upon the treatment or conditions superimposed."} {"id": "PMID:1262489", "title": "Relationship between sex drive and sexual frustration and purpose in life.", "content": "Forty-eight college students (18 males, M age = 24.3, 30 females, M age = 23.5) participated in a study that investigated the relationship between one's sense of purpose in life and sexual attitudes and behavior. The test instruments included the Purpose in Life Test (PIL), a Sex Drive and Interest Scale, and a Sexual Frustration and Maladjustment Scale. Correlations were computed between the students' PIL scores and scores on each of the sex scales. The results indicated no relationship between PIL scores and the scores on the sex drive scale, whereas significant negative correlations were found between PIL scores and the sexual frustration scores for males and for the combined group of males and females. The scores on the PIL and the sexual frustration scale were not related to the students' sex. These results support Frankl's theory that sexual frustration may be a manifestation of a more general existential frustration.", "contents": "Relationship between sex drive and sexual frustration and purpose in life. Forty-eight college students (18 males, M age = 24.3, 30 females, M age = 23.5) participated in a study that investigated the relationship between one's sense of purpose in life and sexual attitudes and behavior. The test instruments included the Purpose in Life Test (PIL), a Sex Drive and Interest Scale, and a Sexual Frustration and Maladjustment Scale. Correlations were computed between the students' PIL scores and scores on each of the sex scales. The results indicated no relationship between PIL scores and the scores on the sex drive scale, whereas significant negative correlations were found between PIL scores and the sexual frustration scores for males and for the combined group of males and females. The scores on the PIL and the sexual frustration scale were not related to the students' sex. These results support Frankl's theory that sexual frustration may be a manifestation of a more general existential frustration."} {"id": "PMID:1262490", "title": "Personality deviancy and prison incarceration.", "content": "This investigation was designed to study personality differences among prison inmates that could be attributed to the number of felony offenses and the length of incarceration. MMPI profiles of 93 inmates of a medium security prison were obtained and analyzed. Special attention was directed to the five MMPI variables K, D, PD, SC, and MA. These five variables taken collectively successfully differentiated first offenders from repeaters and short-term from long-term inmates. The results support the hypothesis that increased incarceration has a harmful effect upon personality.", "contents": "Personality deviancy and prison incarceration. This investigation was designed to study personality differences among prison inmates that could be attributed to the number of felony offenses and the length of incarceration. MMPI profiles of 93 inmates of a medium security prison were obtained and analyzed. Special attention was directed to the five MMPI variables K, D, PD, SC, and MA. These five variables taken collectively successfully differentiated first offenders from repeaters and short-term from long-term inmates. The results support the hypothesis that increased incarceration has a harmful effect upon personality."} {"id": "PMID:1262491", "title": "Child-rearing attitudes of subjects who vary in guilt.", "content": "The present study sought to determine whether high- and low-guilt Ss differ in their child-rearing attitudes. High-guilt Ss were found to be more likely to prefer an overprotective orientation combined with harsh punitive control. In general, attitudes of the high-guilt Ss were seen as more likely to produce psychological disturbance in their children.", "contents": "Child-rearing attitudes of subjects who vary in guilt. The present study sought to determine whether high- and low-guilt Ss differ in their child-rearing attitudes. High-guilt Ss were found to be more likely to prefer an overprotective orientation combined with harsh punitive control. In general, attitudes of the high-guilt Ss were seen as more likely to produce psychological disturbance in their children."} {"id": "PMID:1262492", "title": "Personality profiles in asthma.", "content": "One hundred and fifty-five hospitalized asthma patients were administered the Minnesota Multiphasic Personality Inventory (MMPI) in order to evaluate the existence of common personality characteristics. When the full sample was divided into subgroups according to age, sex, and duration of the illness, it was found that patterns emerged that appeared largely explicable by these variables rather than the asthma per se. The single most frequent pattern observed across these subgroups was a V-shaped configuration of a \"neurotic triad\" (scales 1, 2, and 3). This pattern is not unique to asthma, but is also characteristic of other chronic illness populations and seems to represent a defensive stance in coping with the problems of chronic illness. The findings speak against any stereotypic asthmatic personality. It appears more profitable to investigate individual personality patterns associated with coping styles and their relationship to the illness via behaviors that either maintain or delimit the effects of chronic asthma.", "contents": "Personality profiles in asthma. One hundred and fifty-five hospitalized asthma patients were administered the Minnesota Multiphasic Personality Inventory (MMPI) in order to evaluate the existence of common personality characteristics. When the full sample was divided into subgroups according to age, sex, and duration of the illness, it was found that patterns emerged that appeared largely explicable by these variables rather than the asthma per se. The single most frequent pattern observed across these subgroups was a V-shaped configuration of a \"neurotic triad\" (scales 1, 2, and 3). This pattern is not unique to asthma, but is also characteristic of other chronic illness populations and seems to represent a defensive stance in coping with the problems of chronic illness. The findings speak against any stereotypic asthmatic personality. It appears more profitable to investigate individual personality patterns associated with coping styles and their relationship to the illness via behaviors that either maintain or delimit the effects of chronic asthma."} {"id": "PMID:1262493", "title": "Locus of control as predictive of goal-directed behavior.", "content": "EEO Upward Mobility Program participants were compared with three different control groups along I-E locus of control dimensions. With this instrument and these Ss, no significant differences were found when participation in the program was used as an indicator of goal-directed behavior.", "contents": "Locus of control as predictive of goal-directed behavior. EEO Upward Mobility Program participants were compared with three different control groups along I-E locus of control dimensions. With this instrument and these Ss, no significant differences were found when participation in the program was used as an indicator of goal-directed behavior."} {"id": "PMID:1262494", "title": "Hopelessness, internal-external locus of control, and depression.", "content": "This research examined the relationship between hopelessness, defined as a system of negative expectancies about the future, and two theoretically relevant constructs: internal-external locus of control, and depression. Two samples of 67 and 44 undergraduates were administered the Beck, et al. Hopelessness Scale, the Rotter Internal-External Scale, and the Beck Depression Inventory. The data of both samples supported the predictions that hopelessness would be positively related to external locus of control and to depression.", "contents": "Hopelessness, internal-external locus of control, and depression. This research examined the relationship between hopelessness, defined as a system of negative expectancies about the future, and two theoretically relevant constructs: internal-external locus of control, and depression. Two samples of 67 and 44 undergraduates were administered the Beck, et al. Hopelessness Scale, the Rotter Internal-External Scale, and the Beck Depression Inventory. The data of both samples supported the predictions that hopelessness would be positively related to external locus of control and to depression."} {"id": "PMID:1262495", "title": "Internal-external locus of control and guilt.", "content": "This study examined the relationship between internal-external locus of control and guilt. Ss were 65 male and 137 college undergraduates who completed the Rotter I-E scale and the Mosher Hostility and Morality-Conscience Guilt Scales. Results demonstrated that internals reported a higher degree of hostility guilt than externals. Also, females expressed greater hostility and morality-conscience guilt than males.", "contents": "Internal-external locus of control and guilt. This study examined the relationship between internal-external locus of control and guilt. Ss were 65 male and 137 college undergraduates who completed the Rotter I-E scale and the Mosher Hostility and Morality-Conscience Guilt Scales. Results demonstrated that internals reported a higher degree of hostility guilt than externals. Also, females expressed greater hostility and morality-conscience guilt than males."} {"id": "PMID:1262496", "title": "Augmenting-reducing and sensation seeking: a test of Sales' hypothesis.", "content": "Physiologically, augmenters amplify incoming stimulation, while reducers attenuate such stimulation. Sales has theorized that this characteristic is a determinant of an individual's need for stimulation and that reducers require more actual stimulation to reach this perceived optimal level than do augmenters. The theory predicts that measures of these characteristics would be correlated. The absolute auditory threshold was used as a measure of augmenting-reducing and the Sensation-Seeking Scale as a measure of need for stimulation in a study that tested 42 college students. The theoretical prediction was not confirmed. The bearing of these negative findings upon Sales' theory and the possibility that the auditory threshold is not a valid measure of augmenting-reducing were discussed.", "contents": "Augmenting-reducing and sensation seeking: a test of Sales' hypothesis. Physiologically, augmenters amplify incoming stimulation, while reducers attenuate such stimulation. Sales has theorized that this characteristic is a determinant of an individual's need for stimulation and that reducers require more actual stimulation to reach this perceived optimal level than do augmenters. The theory predicts that measures of these characteristics would be correlated. The absolute auditory threshold was used as a measure of augmenting-reducing and the Sensation-Seeking Scale as a measure of need for stimulation in a study that tested 42 college students. The theoretical prediction was not confirmed. The bearing of these negative findings upon Sales' theory and the possibility that the auditory threshold is not a valid measure of augmenting-reducing were discussed."} {"id": "PMID:1262497", "title": "Personality characteristics of death-row prison inmates.", "content": "An analysis of MMPI differences that appeared between a sample of 34 male inmates sentenced to be executed by asphyxiation and a representative prison population sample of 2,551 male inmates revealed that the profiles of both groups were indicative of a behavior disorder. The Death Row inmates presented significantly higher elevations on the PA and SC scales. Further evaluation of the subscale scores for the PA and SC scales demonstrated that the test responses of the Death Row inmates to these two scales were related more closely to feelings of resentment, hopelessness, failure, frustration, isolation and social alienation rather than to any delusional, dissociative or bizarre thought processes. Evaluation of the Death Row inmates' responses to four additional MMPI scales supported the previously made contention that the primary concern was with indices of a behavior disorder associated with the situational stress of being confined on Death Row to await execution rather than with indices of psychotic-appearing thought processes. In light of these findings it is felt that high PA and SC profiles scored by inmates who are awaiting execution should be supported by other MMPI scale, subscale and additional scale configurations, as well as other clinical inferences, before psychosis-related diagnoses are made.", "contents": "Personality characteristics of death-row prison inmates. An analysis of MMPI differences that appeared between a sample of 34 male inmates sentenced to be executed by asphyxiation and a representative prison population sample of 2,551 male inmates revealed that the profiles of both groups were indicative of a behavior disorder. The Death Row inmates presented significantly higher elevations on the PA and SC scales. Further evaluation of the subscale scores for the PA and SC scales demonstrated that the test responses of the Death Row inmates to these two scales were related more closely to feelings of resentment, hopelessness, failure, frustration, isolation and social alienation rather than to any delusional, dissociative or bizarre thought processes. Evaluation of the Death Row inmates' responses to four additional MMPI scales supported the previously made contention that the primary concern was with indices of a behavior disorder associated with the situational stress of being confined on Death Row to await execution rather than with indices of psychotic-appearing thought processes. In light of these findings it is felt that high PA and SC profiles scored by inmates who are awaiting execution should be supported by other MMPI scale, subscale and additional scale configurations, as well as other clinical inferences, before psychosis-related diagnoses are made."} {"id": "PMID:1262498", "title": "Appreciation of risqu\u00e9 cartoon humor in male and female repressors and sensitizers.", "content": "Male and female nondefensive sensitizers, defensive repressors and nondefensive repressors were instructed to rate the degree of humor in each of 40 cartoons. The cartoons, which previously had been equated for funniness, either contained sexual themes or were completely devoid of sexual content. As hypothesized, female repressors rated sexual cartoons as less humorous than nonsexual cartoons. In addition, female sensitizers rated sexual cartoons as funnier than did female repressors. No differences were found for male Ss. Results were interpreted according to an approach-avoidance model of repression-sensitization.", "contents": "Appreciation of risqu\u00e9 cartoon humor in male and female repressors and sensitizers. Male and female nondefensive sensitizers, defensive repressors and nondefensive repressors were instructed to rate the degree of humor in each of 40 cartoons. The cartoons, which previously had been equated for funniness, either contained sexual themes or were completely devoid of sexual content. As hypothesized, female repressors rated sexual cartoons as less humorous than nonsexual cartoons. In addition, female sensitizers rated sexual cartoons as funnier than did female repressors. No differences were found for male Ss. Results were interpreted according to an approach-avoidance model of repression-sensitization."} {"id": "PMID:1262499", "title": "The personal beliefs inventory: a factor-analytic study.", "content": "An exploratory study into the factor structure of the Personal Beliefs Inventory (PBI) was conducted. The Wherry-Wherry hierarchical factor analysis was employed to analyze the 60 X 60 intercorrelation matrix of PBI items. The hierarchical solution revealed a general PBI factor structure that implies low self-worth, an attitude consistent with Ellis's theory of emotional disturbance. In addition, six interpretable lower-order factors were revealed and discussed.", "contents": "The personal beliefs inventory: a factor-analytic study. An exploratory study into the factor structure of the Personal Beliefs Inventory (PBI) was conducted. The Wherry-Wherry hierarchical factor analysis was employed to analyze the 60 X 60 intercorrelation matrix of PBI items. The hierarchical solution revealed a general PBI factor structure that implies low self-worth, an attitude consistent with Ellis's theory of emotional disturbance. In addition, six interpretable lower-order factors were revealed and discussed."} {"id": "PMID:1262500", "title": "Personality correlates of WAIS performance.", "content": "The relationships between two of Cattell's second-stratum factors, Cortertia and Temperamental Independence, and WAIS scores were investigated for 122 men and 127 women. For men, both Cortertia and Temperamental Independence were related significantly to WAIS scores. For women, Temperamental Independence, but not Cortertia, correlated significantly with WAIS scores. The variability in the degree of relationship between the individual subtests and the personality factors was noted, and the cross-lagged panel correlation methodology was suggested as a possible approach to investigate the causal connections between personality factors and abilities.", "contents": "Personality correlates of WAIS performance. The relationships between two of Cattell's second-stratum factors, Cortertia and Temperamental Independence, and WAIS scores were investigated for 122 men and 127 women. For men, both Cortertia and Temperamental Independence were related significantly to WAIS scores. For women, Temperamental Independence, but not Cortertia, correlated significantly with WAIS scores. The variability in the degree of relationship between the individual subtests and the personality factors was noted, and the cross-lagged panel correlation methodology was suggested as a possible approach to investigate the causal connections between personality factors and abilities."} {"id": "PMID:1262501", "title": "The Bender-Gestalt and the Halstead-Reitan battery: a case study.", "content": "A single case with severe static left hemisphere cerebral damage was used to illustrate some deficiencies in the Bender-Gestalt (B-G) test and to compare its results with the Halstead-Reitan battery. The B-G did not indicate the existence of any brain damage because visuoconstructional tests evidently are related directly only to the right parietal area. The Halstead indicated the existance of brain damage, the amount of impairment to various mental functions, the location, process status, and general type of pathology and provided an evaluation of residual functions. Used as a screening test, the B-G is useful because it measures nondominant functions and is a \"don't hold\" test. The Halstead should be used when a more complete evaluation or critical test for brain damage is required.", "contents": "The Bender-Gestalt and the Halstead-Reitan battery: a case study. A single case with severe static left hemisphere cerebral damage was used to illustrate some deficiencies in the Bender-Gestalt (B-G) test and to compare its results with the Halstead-Reitan battery. The B-G did not indicate the existence of any brain damage because visuoconstructional tests evidently are related directly only to the right parietal area. The Halstead indicated the existance of brain damage, the amount of impairment to various mental functions, the location, process status, and general type of pathology and provided an evaluation of residual functions. Used as a screening test, the B-G is useful because it measures nondominant functions and is a \"don't hold\" test. The Halstead should be used when a more complete evaluation or critical test for brain damage is required."} {"id": "PMID:1262502", "title": "Ethnicity, socioeconomic status, and pattern of WISC scores as variables that affect psychologists' estimates of \"effective intelligence\".", "content": "Psychologists estimated \"true IQs\" or \"effective intelligence\" from WISC profiles that varied for ethnicity (black, Mexican-American, or white), social class (lower or middle), profile (three scatter patterns), and direction of Verbal-Performance Scale discrepancy. Psychologists gave higher IQ estimates to black and Mexican-American children's profiles than to the same profiles of white children. Social class was not a significant factor. Profiles with much scatter received higher IQs than profiles with limited scatter. The pattern of subtest scores also affected estimates, while the direction of the Verbal-Performance discrepancy was not significant. Finally, the WISC was judged to be more valid for white than for black and Mexican-American children. Explanations of the findings were discussed.", "contents": "Ethnicity, socioeconomic status, and pattern of WISC scores as variables that affect psychologists' estimates of \"effective intelligence\". Psychologists estimated \"true IQs\" or \"effective intelligence\" from WISC profiles that varied for ethnicity (black, Mexican-American, or white), social class (lower or middle), profile (three scatter patterns), and direction of Verbal-Performance Scale discrepancy. Psychologists gave higher IQ estimates to black and Mexican-American children's profiles than to the same profiles of white children. Social class was not a significant factor. Profiles with much scatter received higher IQs than profiles with limited scatter. The pattern of subtest scores also affected estimates, while the direction of the Verbal-Performance discrepancy was not significant. Finally, the WISC was judged to be more valid for white than for black and Mexican-American children. Explanations of the findings were discussed."} {"id": "PMID:1262503", "title": "Cognitive deficits in patients with unilateral war-related frontal lobe lesions.", "content": "The findings of this study may be summarized as follows: (1) No significant general cognitive impairment occurred in S samples with unilateral frontal lobe lesions; (2) Impairment of cognitive performance was greater in Ss with lesions posterior to the Fissure of Rolondo than in well-matched Ss with frontal lobe lesions; (3) Specific cognitive deficits are infrequent in Ss with frontal lobe lesions; (4) No significant differential impairment of cognitive performance was associated with hemispheric lateralization of frontal lesions; and (5) No significant differential impairment of verbal and nonverbal performance was associated with hemispheric lateralization of frontal lesions.", "contents": "Cognitive deficits in patients with unilateral war-related frontal lobe lesions. The findings of this study may be summarized as follows: (1) No significant general cognitive impairment occurred in S samples with unilateral frontal lobe lesions; (2) Impairment of cognitive performance was greater in Ss with lesions posterior to the Fissure of Rolondo than in well-matched Ss with frontal lobe lesions; (3) Specific cognitive deficits are infrequent in Ss with frontal lobe lesions; (4) No significant differential impairment of cognitive performance was associated with hemispheric lateralization of frontal lesions; and (5) No significant differential impairment of verbal and nonverbal performance was associated with hemispheric lateralization of frontal lesions."} {"id": "PMID:1262504", "title": "The expectation-reality discrepancy and premature termination from psychotherapy.", "content": "The confirmation or disconfirmation of initial client expectation with regard to the psychotherapy process was related to drop out from psychotherapy for clients of a university psychological clinic. Previous hypotheses and research findings emphasized the existence of a linear relationship between expectancy confirmation or disconfirmation and drop out from psychotherapy. Contrary to those findings, the present study revealed significant curvilinear relationships between the two variables in question. Cultural and intellectual differences between the lower-class patient population, which exhibited linear relationships between expectancy confirmation or disconfirmation and drop out, and the present college population, which exhibited curvilinear relationships between the variables under investigation, were discussed as factors that contributed to the divergent findings of the present study.", "contents": "The expectation-reality discrepancy and premature termination from psychotherapy. The confirmation or disconfirmation of initial client expectation with regard to the psychotherapy process was related to drop out from psychotherapy for clients of a university psychological clinic. Previous hypotheses and research findings emphasized the existence of a linear relationship between expectancy confirmation or disconfirmation and drop out from psychotherapy. Contrary to those findings, the present study revealed significant curvilinear relationships between the two variables in question. Cultural and intellectual differences between the lower-class patient population, which exhibited linear relationships between expectancy confirmation or disconfirmation and drop out, and the present college population, which exhibited curvilinear relationships between the variables under investigation, were discussed as factors that contributed to the divergent findings of the present study."} {"id": "PMID:1262505", "title": "Presenting problems of students at a university psychological clinic.", "content": "Previous research in college student mental health indicates that most psychological problems stem from the academic area of the student's life. However, many previous studies focused upon the general college population and did not consider the problems of students who are receiving mental health services. In the present study, college students who sought psychological counseling at a university clinic were asked to rate the severity of their problems in 10 problem areas and to provide written descriptions of specific problems within each area. Clients' disturbance ratings and clinical judges' ratings of the clients' written problems revealed that problems in the area of self and self-satisfaction were the most severe problems for college students who sought psychological services.", "contents": "Presenting problems of students at a university psychological clinic. Previous research in college student mental health indicates that most psychological problems stem from the academic area of the student's life. However, many previous studies focused upon the general college population and did not consider the problems of students who are receiving mental health services. In the present study, college students who sought psychological counseling at a university clinic were asked to rate the severity of their problems in 10 problem areas and to provide written descriptions of specific problems within each area. Clients' disturbance ratings and clinical judges' ratings of the clients' written problems revealed that problems in the area of self and self-satisfaction were the most severe problems for college students who sought psychological services."} {"id": "PMID:1262506", "title": "Effects of physical training on mood.", "content": "Thirty-six adult men at high risk of coronary artery disease were assigned to either an exercise or no exercise (control) group. Improvements in physical fitness were accompanied by improvements on two mood measures, anxiety and depression. No change was found on measures of adjustment, self-confidence and body image.", "contents": "Effects of physical training on mood. Thirty-six adult men at high risk of coronary artery disease were assigned to either an exercise or no exercise (control) group. Improvements in physical fitness were accompanied by improvements on two mood measures, anxiety and depression. No change was found on measures of adjustment, self-confidence and body image."} {"id": "PMID:1262507", "title": "Avowed approval of psychotherapy session content among novice A and B therapists.", "content": "The present data thus affirm previous research that attributes a more accepting style to A therapists. Specifically, A therapists expressed greater avowed approval of in-therapy discussion of unusual thought and behavior, subjective material such as dreams and fears, and certain nontraditional attitudes toward divorce and feminine roles. Similarly, psychology trainees on the whole expressed greater approval of unusual and subjective material and were more favorable in their attitude toward discussion of certain family difficulties and therapeutic progress than were psychiatry residents.", "contents": "Avowed approval of psychotherapy session content among novice A and B therapists. The present data thus affirm previous research that attributes a more accepting style to A therapists. Specifically, A therapists expressed greater avowed approval of in-therapy discussion of unusual thought and behavior, subjective material such as dreams and fears, and certain nontraditional attitudes toward divorce and feminine roles. Similarly, psychology trainees on the whole expressed greater approval of unusual and subjective material and were more favorable in their attitude toward discussion of certain family difficulties and therapeutic progress than were psychiatry residents."} {"id": "PMID:1262508", "title": "The Democratic Values Scale and professional affiliation.", "content": "Therapists from four professional groups--nursing, psychiatry, psychology and social work--were compared on Lerner's Democratic Values Scale. Significant professional differences were found on this scale. The findings raise questions about the predictive power of this scale when a variety of mental health professionals are studied.", "contents": "The Democratic Values Scale and professional affiliation. Therapists from four professional groups--nursing, psychiatry, psychology and social work--were compared on Lerner's Democratic Values Scale. Significant professional differences were found on this scale. The findings raise questions about the predictive power of this scale when a variety of mental health professionals are studied."} {"id": "PMID:1262509", "title": "Neurotic anxiety, pronoun usage and stress.", "content": "The use of the pronoun \"I\" when a speaker refers to his own actions, thoughts, or emotions is appropriate. Omission of the pronoun or the use of \"you\" or \"it\" may be taken as an indicant of psychological distantiation. This study examines the effects of stress and neurotic anxiety on pronoun usage. Forty-five male and female undergraduate Ss enrolled at Virginia Commonwealth University were selected randomly from 172 volunteers assessed for neurotic anxiety level as measured by the Maudsley Personality Inventory and Taylor Manifest Anxiety Scale. Treatment consisted of asking 20 emotionally charged questions, 10 of which were neutral baseline questions and the other 10 were either negative, neutral, or positive in stress. Responses were tape recorded and transcribed. It was found that negative stress interacting with medium level anxiety neurotics significantly increased distantiation above baseline levels. A hypothesis to explain the results was offered.", "contents": "Neurotic anxiety, pronoun usage and stress. The use of the pronoun \"I\" when a speaker refers to his own actions, thoughts, or emotions is appropriate. Omission of the pronoun or the use of \"you\" or \"it\" may be taken as an indicant of psychological distantiation. This study examines the effects of stress and neurotic anxiety on pronoun usage. Forty-five male and female undergraduate Ss enrolled at Virginia Commonwealth University were selected randomly from 172 volunteers assessed for neurotic anxiety level as measured by the Maudsley Personality Inventory and Taylor Manifest Anxiety Scale. Treatment consisted of asking 20 emotionally charged questions, 10 of which were neutral baseline questions and the other 10 were either negative, neutral, or positive in stress. Responses were tape recorded and transcribed. It was found that negative stress interacting with medium level anxiety neurotics significantly increased distantiation above baseline levels. A hypothesis to explain the results was offered."} {"id": "PMID:1262510", "title": "Assessing intertrainer effects on the Empathic Understanding Scale: training the trainer.", "content": "The purpose of this study was to develop a procedure that would provide a preliminary assessment of the level of intertrainer agreement on the Empathic Understanding scale. To illustrate the proposed procedure, a pilot study was undertaken in which 30 excerpts of helping interactions that included the client's statement, therapist response, and client's subsequent response were rated by experienced raters trained by a Carkhuff trainer and a non-Carkhuff trainer. Results indicated that raters trained by different trainers make significantly different judgments about the level of therapist empathy at high levels of empathy. Results of this study were discussed in light of possible scale reliability and construct validity problems. A detailed description and rationale of the proposed procedure was outlined.", "contents": "Assessing intertrainer effects on the Empathic Understanding Scale: training the trainer. The purpose of this study was to develop a procedure that would provide a preliminary assessment of the level of intertrainer agreement on the Empathic Understanding scale. To illustrate the proposed procedure, a pilot study was undertaken in which 30 excerpts of helping interactions that included the client's statement, therapist response, and client's subsequent response were rated by experienced raters trained by a Carkhuff trainer and a non-Carkhuff trainer. Results indicated that raters trained by different trainers make significantly different judgments about the level of therapist empathy at high levels of empathy. Results of this study were discussed in light of possible scale reliability and construct validity problems. A detailed description and rationale of the proposed procedure was outlined."} {"id": "PMID:1262511", "title": "Interviewee matching of interviewer temporal speech behaviors as related to perceived empathy, warmth, and genuineness.", "content": "The present study used an experimental analogue of the initial interview to examine the relationship of therapist durational speech characteristics to therapist empathy, warmth, genuineness and the state of the \"therapeutic relationship\" as rated by the interviewee. Cross-validated results revealed a modest direct relationship between interviewee speech modelling (DOU) and all process variables examined, with the exception of genuineness. Efficacy of the automated standardized interview as a research tool also was demonstrated. The results implicate the future examination of the relationship between therapist-client speech and silence measures and process variables.", "contents": "Interviewee matching of interviewer temporal speech behaviors as related to perceived empathy, warmth, and genuineness. The present study used an experimental analogue of the initial interview to examine the relationship of therapist durational speech characteristics to therapist empathy, warmth, genuineness and the state of the \"therapeutic relationship\" as rated by the interviewee. Cross-validated results revealed a modest direct relationship between interviewee speech modelling (DOU) and all process variables examined, with the exception of genuineness. Efficacy of the automated standardized interview as a research tool also was demonstrated. The results implicate the future examination of the relationship between therapist-client speech and silence measures and process variables."} {"id": "PMID:1262512", "title": "Fantasy in individuals who smoke, stopped smoking, and never smoked.", "content": "The present study advanced the hypothesis that individuals who smoke tend to fantasize more than those who have stopped smoking or never smoked. Ninety males and 90 females, with each sex divided into three categories (smokers, stopped smokers, and never smoked) were used. Results of the study supported the hypothesis when applied to male smokers, but not to female smokers. While male smokers tended to fantasize most, the opposite was found for the female smoker, who fantasized least. This was also true in the specific area of achievement.", "contents": "Fantasy in individuals who smoke, stopped smoking, and never smoked. The present study advanced the hypothesis that individuals who smoke tend to fantasize more than those who have stopped smoking or never smoked. Ninety males and 90 females, with each sex divided into three categories (smokers, stopped smokers, and never smoked) were used. Results of the study supported the hypothesis when applied to male smokers, but not to female smokers. While male smokers tended to fantasize most, the opposite was found for the female smoker, who fantasized least. This was also true in the specific area of achievement."} {"id": "PMID:1262513", "title": "The efficacy of programmed instruction in the training of paraprofessionals.", "content": "The authors assessed the efficacy of a self-instructional psychiatric learning program to provide training for paraprofessional psychiatric personnel. The self-regulated learning system, which originally was developed to train medical students, was designed to impart basic psychiatric knowledge and diagnostic skills. Changes along personality dimensions that occurred as a function of participating in the programmed learning project also were examined. Participation in this program was associated with substantial pre-post changes in dogmatism and locus of control for males as well as significant increments in psychiatric knowledge and diagnostic skills for the group as a whole. The benefits derived from this easily administered training procedure suggest its feasible inclusion in paraprofessional inservice training programs.", "contents": "The efficacy of programmed instruction in the training of paraprofessionals. The authors assessed the efficacy of a self-instructional psychiatric learning program to provide training for paraprofessional psychiatric personnel. The self-regulated learning system, which originally was developed to train medical students, was designed to impart basic psychiatric knowledge and diagnostic skills. Changes along personality dimensions that occurred as a function of participating in the programmed learning project also were examined. Participation in this program was associated with substantial pre-post changes in dogmatism and locus of control for males as well as significant increments in psychiatric knowledge and diagnostic skills for the group as a whole. The benefits derived from this easily administered training procedure suggest its feasible inclusion in paraprofessional inservice training programs."} {"id": "PMID:1262514", "title": "Longitudinal investigation of changes in interviewing performance of medical students.", "content": "The purposes were to determine the direction and extent of change in a medical student's ability to relate to patients between the sophomore and senior years, to assess the degree of predicted senior year performance from the sophomore year, and to determine the reliability of two major methods: interaction analysis (IA) and global faculty ratings. Twenty-two students were video-taped conducting two 10-minute interviews with a programmed patient: one as a sophomore, the other as a senior. The results for the interaction analysis method showed that the students were more directive, used more exploratory behaviors, were less supportive and more highly rated by the patients (actors) in the senior year. The physician-evaluators' global ratings indicated the students were more supportive, empathetic and open-ended, had fewer uncommon words, but conducted better overall interviews as seniors. The IA method was more reliable than global faculty ratings.", "contents": "Longitudinal investigation of changes in interviewing performance of medical students. The purposes were to determine the direction and extent of change in a medical student's ability to relate to patients between the sophomore and senior years, to assess the degree of predicted senior year performance from the sophomore year, and to determine the reliability of two major methods: interaction analysis (IA) and global faculty ratings. Twenty-two students were video-taped conducting two 10-minute interviews with a programmed patient: one as a sophomore, the other as a senior. The results for the interaction analysis method showed that the students were more directive, used more exploratory behaviors, were less supportive and more highly rated by the patients (actors) in the senior year. The physician-evaluators' global ratings indicated the students were more supportive, empathetic and open-ended, had fewer uncommon words, but conducted better overall interviews as seniors. The IA method was more reliable than global faculty ratings."} {"id": "PMID:1262515", "title": "Are men therapists soft on empathy? Two studies in feminine understanding.", "content": "A serendipitous finding and a replication among successive populations of clinical-counseling practicum students suggest that the typical female therapist communicates more empathically than her male colleague. In the first study, reactions of 8 women trainees were evaluated as more empathic than those of 10 men counterparts. Despite control for sex-typed handwriting cues in the second study, 8 male novitiates' responses were assessed as less empathic than those of 8 females. The results are consistent with the notion of differential sex-role prescriptions for interpersonal sensitivity.", "contents": "Are men therapists soft on empathy? Two studies in feminine understanding. A serendipitous finding and a replication among successive populations of clinical-counseling practicum students suggest that the typical female therapist communicates more empathically than her male colleague. In the first study, reactions of 8 women trainees were evaluated as more empathic than those of 10 men counterparts. Despite control for sex-typed handwriting cues in the second study, 8 male novitiates' responses were assessed as less empathic than those of 8 females. The results are consistent with the notion of differential sex-role prescriptions for interpersonal sensitivity."} {"id": "PMID:1262516", "title": "Expectations, experiencing and change in psychotherapy.", "content": "The relationships of client prognostic expectations and of level of Experiencing in psychotherapy with three variables of therapeutic change were explored in a correlational study that used 26 volunteer Ss who were in treatment with experienced therapists. A positive relationship was found between prognostic expectation and perceived improvement and a negative relationship between Experiencing and perceived improvement. The data also suggested positive relationships between Experiencing and cognitive change and attitude and cognitive change, while they provided no evidence for a relation between expectations and cognitive change.", "contents": "Expectations, experiencing and change in psychotherapy. The relationships of client prognostic expectations and of level of Experiencing in psychotherapy with three variables of therapeutic change were explored in a correlational study that used 26 volunteer Ss who were in treatment with experienced therapists. A positive relationship was found between prognostic expectation and perceived improvement and a negative relationship between Experiencing and perceived improvement. The data also suggested positive relationships between Experiencing and cognitive change and attitude and cognitive change, while they provided no evidence for a relation between expectations and cognitive change."} {"id": "PMID:1262517", "title": "A comparison of two treatments for depression: the antidepressive program vs. traditional therapy.", "content": "This study compared a traditional therapy for depression with Antidepressive therapy, a regime of meaningless, boring work designed to provoke the patient to an assertive expression of anger. The Ss were 32 neurotic and 24 psychotic patients at the Tuscaloosa, Alabama Veterans Administration Hospital. Improvement was measured by scores on the Purpose-In-Life Test (PIL) and the Self-Rating Depression Scale. All patient groups improved significantly within a 1-week period. Neurotics treated on the Antidepressive program improved significantly more than neurotics treated on the Traditional program. However, the data failed to indicate that either program was significantly more effective than the other in the treatment of psychotics.", "contents": "A comparison of two treatments for depression: the antidepressive program vs. traditional therapy. This study compared a traditional therapy for depression with Antidepressive therapy, a regime of meaningless, boring work designed to provoke the patient to an assertive expression of anger. The Ss were 32 neurotic and 24 psychotic patients at the Tuscaloosa, Alabama Veterans Administration Hospital. Improvement was measured by scores on the Purpose-In-Life Test (PIL) and the Self-Rating Depression Scale. All patient groups improved significantly within a 1-week period. Neurotics treated on the Antidepressive program improved significantly more than neurotics treated on the Traditional program. However, the data failed to indicate that either program was significantly more effective than the other in the treatment of psychotics."} {"id": "PMID:1262518", "title": "Jehovah's Witnesses and human tissue donation.", "content": "Because of their religious beliefs members of the Jehovah's Witnesses sect do not permit human tissue donation, not even such a routine and life-saving procedure as blood transfusion. A group of 30 adult Jehovah's Witnesses was compared with groups of donors and nondonors on a variety of personality measures. Donor status is associated with a well-integrated body image and acceptance of mortality, while nondonor status correlates with a less-well-integrated body image, concern about body integrity, and anxiety about death. However, while Jehovah's Witnesses vigorously oppose human tissue donation they appear to do so on strong religious grounds rather than because of personal anxiety and thus are dissimilar to non-donors at large.", "contents": "Jehovah's Witnesses and human tissue donation. Because of their religious beliefs members of the Jehovah's Witnesses sect do not permit human tissue donation, not even such a routine and life-saving procedure as blood transfusion. A group of 30 adult Jehovah's Witnesses was compared with groups of donors and nondonors on a variety of personality measures. Donor status is associated with a well-integrated body image and acceptance of mortality, while nondonor status correlates with a less-well-integrated body image, concern about body integrity, and anxiety about death. However, while Jehovah's Witnesses vigorously oppose human tissue donation they appear to do so on strong religious grounds rather than because of personal anxiety and thus are dissimilar to non-donors at large."} {"id": "PMID:1262519", "title": "Schizophrenic behavior as a function of role expectation.", "content": "The hypothesis that the behavior of schizophrenic patients is determined in part by role expectation was investigated. The Holtzman Inkblot Technique and a word association task were administered to the same patients under two conditions: (1) Ss were led to believe that the interviewer was unaware of their patient status and expected them to behave in a normal manner; and (2) Ss were informed that the interviewer was interested in their behavior as mental patients. The results indicated that there was less evidence of pathology on the Holtzman when Ss were told that the interviewer expected them to behave in a normal manner. More specifically, there was less Pathognomonic Verbalization and more Form Appropriateness in the normal expectation condition. The findings are consistent with current views as to the pathogenic effects of labeling and institutionalization.", "contents": "Schizophrenic behavior as a function of role expectation. The hypothesis that the behavior of schizophrenic patients is determined in part by role expectation was investigated. The Holtzman Inkblot Technique and a word association task were administered to the same patients under two conditions: (1) Ss were led to believe that the interviewer was unaware of their patient status and expected them to behave in a normal manner; and (2) Ss were informed that the interviewer was interested in their behavior as mental patients. The results indicated that there was less evidence of pathology on the Holtzman when Ss were told that the interviewer expected them to behave in a normal manner. More specifically, there was less Pathognomonic Verbalization and more Form Appropriateness in the normal expectation condition. The findings are consistent with current views as to the pathogenic effects of labeling and institutionalization."} {"id": "PMID:1262520", "title": "Reliability of the Koppitz scoring system for the Bender Gestalt Test.", "content": "This study investigated the test-retest reliability of the Koppitz scoring system with Bender Gestalt protocols of adult retardates. Results of a sample of 74 adult retardates yielded a correlation of .80 over an interval of 8 to 146 months. A directional measure of change between error scores on the first and second administrations was not significant, which suggests that the test-retest reliability coefficient is an accurate estimate of the Koppitz scoring system for adult retardates. Scorer reliability for three independent scorers ranged from .92 to .95, which suggests comparability to other investigations with different populations.", "contents": "Reliability of the Koppitz scoring system for the Bender Gestalt Test. This study investigated the test-retest reliability of the Koppitz scoring system with Bender Gestalt protocols of adult retardates. Results of a sample of 74 adult retardates yielded a correlation of .80 over an interval of 8 to 146 months. A directional measure of change between error scores on the first and second administrations was not significant, which suggests that the test-retest reliability coefficient is an accurate estimate of the Koppitz scoring system for adult retardates. Scorer reliability for three independent scorers ranged from .92 to .95, which suggests comparability to other investigations with different populations."} {"id": "PMID:1262521", "title": "An empirical typology of heroin abusers.", "content": "The MMPI profiles of 59 participants in a VA Drug Abuse Program were analyzed. A total of eight types were defined by factor analysis. Three of the groups accounted for 60% of the Ss. The three groups had profiles that involved elevations on scales 2, 4, 8, and 9.", "contents": "An empirical typology of heroin abusers. The MMPI profiles of 59 participants in a VA Drug Abuse Program were analyzed. A total of eight types were defined by factor analysis. Three of the groups accounted for 60% of the Ss. The three groups had profiles that involved elevations on scales 2, 4, 8, and 9."} {"id": "PMID:1262522", "title": "Personality characteristics related to treatment decisions among inpatient alcoholics: a non-relationship.", "content": "A battery of standard personality and experimental research scales was administered to 110 male alcoholic inpatients. No differences were found on the 30 scale scores derived from the tests among three groups with differential treatment dispositions: (1) those who discontinued treatment after a 2-week evaluation period; (2) those who chose to remain for a 60-day treatment program, but discontinued prior to completion; and (3) those who chose and did complete the 60-day program. It was suggested that attrition from an inpatient alcoholism program might be predicted better by a multivariate approach that used demographic, life history, psychosocial and personality variables as predictors.", "contents": "Personality characteristics related to treatment decisions among inpatient alcoholics: a non-relationship. A battery of standard personality and experimental research scales was administered to 110 male alcoholic inpatients. No differences were found on the 30 scale scores derived from the tests among three groups with differential treatment dispositions: (1) those who discontinued treatment after a 2-week evaluation period; (2) those who chose to remain for a 60-day treatment program, but discontinued prior to completion; and (3) those who chose and did complete the 60-day program. It was suggested that attrition from an inpatient alcoholism program might be predicted better by a multivariate approach that used demographic, life history, psychosocial and personality variables as predictors."} {"id": "PMID:1262523", "title": "Comments on the relationship between locus of control and alcohol abuse.", "content": "Studies that report conflicting relationships between alcohol abuse and locus of control were reviewed. Possible explanations for the results were presented, as were data that indicate that locus of control may be related to age and to social desirability, but not to alcohol abuse. It was suggested that in the absence of a clear theoretical rationale for relating locus of control to alcohol abuse, the contradictory findings are not surprising.", "contents": "Comments on the relationship between locus of control and alcohol abuse. Studies that report conflicting relationships between alcohol abuse and locus of control were reviewed. Possible explanations for the results were presented, as were data that indicate that locus of control may be related to age and to social desirability, but not to alcohol abuse. It was suggested that in the absence of a clear theoretical rationale for relating locus of control to alcohol abuse, the contradictory findings are not surprising."} {"id": "PMID:1262524", "title": "Frequency of MMPI two-point codes in a large alcoholic sample.", "content": "The MMPI two-point codes of 1,009 male Caucasian inpatient alcoholics were examined. Although the mean profile was 4-2, analysis of individual profiles revealed that 79% of the profiles were classified differently from the mean profile. These findings indicate that alcoholics are a heterogeneous group with respect to the MMPI. Some of the most frequently occurring codetypes seem to be associated with widely different behavioral descriptions, which leads to the inference that alcoholics are heterogeneous with respect to personality characteristics as well.", "contents": "Frequency of MMPI two-point codes in a large alcoholic sample. The MMPI two-point codes of 1,009 male Caucasian inpatient alcoholics were examined. Although the mean profile was 4-2, analysis of individual profiles revealed that 79% of the profiles were classified differently from the mean profile. These findings indicate that alcoholics are a heterogeneous group with respect to the MMPI. Some of the most frequently occurring codetypes seem to be associated with widely different behavioral descriptions, which leads to the inference that alcoholics are heterogeneous with respect to personality characteristics as well."} {"id": "PMID:1262525", "title": "Discriminating alcoholic and nonalcoholic patients with conventional and factored MMPI scales: a comparison.", "content": "The factor scales were significantly more accurate than the conventional clinical scales in discriminating alcoholic from nonalcoholic patients. Whereas no single clinical scale emerged as highly important to the discrimination, Factor III emerged as very important to it. The possibility that Factor III represents an \"alcoholic\" factor was raised. From this study, it appears that the factor scales represent a more refined scoring version of the MMPI item pool.", "contents": "Discriminating alcoholic and nonalcoholic patients with conventional and factored MMPI scales: a comparison. The factor scales were significantly more accurate than the conventional clinical scales in discriminating alcoholic from nonalcoholic patients. Whereas no single clinical scale emerged as highly important to the discrimination, Factor III emerged as very important to it. The possibility that Factor III represents an \"alcoholic\" factor was raised. From this study, it appears that the factor scales represent a more refined scoring version of the MMPI item pool."} {"id": "PMID:1262526", "title": "Exclusion of subjects with F scores at or above 16 in MMPI research on alcoholism.", "content": "The results of these comparisons that used the MacAndrew and Holmes scales suggest that the practice of excluding Ss with F scores at or above 16 may result in the discarding of data on alcoholic and problem-drinking Ss with no appreciable gain in the statistical differentiation of the remaining Ss. In the case of the Hampton scale, application of the rule results in nonsignificant statistical results. Furthermore, the F scale differentiated the groups more effectively than did the Hampton scale. It is suggested that MMPI investigators who use the MacAndrew and other alcoholism scales reexamine the appropriateness of MacAndrew's exclusion rule for their particular samples.", "contents": "Exclusion of subjects with F scores at or above 16 in MMPI research on alcoholism. The results of these comparisons that used the MacAndrew and Holmes scales suggest that the practice of excluding Ss with F scores at or above 16 may result in the discarding of data on alcoholic and problem-drinking Ss with no appreciable gain in the statistical differentiation of the remaining Ss. In the case of the Hampton scale, application of the rule results in nonsignificant statistical results. Furthermore, the F scale differentiated the groups more effectively than did the Hampton scale. It is suggested that MMPI investigators who use the MacAndrew and other alcoholism scales reexamine the appropriateness of MacAndrew's exclusion rule for their particular samples."} {"id": "PMID:1262527", "title": "Changes in perceived and experienced control among inpatient alcoholics.", "content": "The Locus of Control and Experienced Control Scales were administered to 40 alcoholics shortly after admission to a rehabilitation program and again after approximately 6 weeks of treatment. During the course of treatment, the Ss evidenced an overall shift toward a more internal locus of control, an increase in the magnitude and relative degree of control experienced over interpersonal and intrapersonal pressures, and a decrease in the magnitude of control exerted on them by such pressures. The overall increase in the proportionate control experienced appeared to be accounted for by shifts made by those Ss who entered treatment with an initially internal locus of control.", "contents": "Changes in perceived and experienced control among inpatient alcoholics. The Locus of Control and Experienced Control Scales were administered to 40 alcoholics shortly after admission to a rehabilitation program and again after approximately 6 weeks of treatment. During the course of treatment, the Ss evidenced an overall shift toward a more internal locus of control, an increase in the magnitude and relative degree of control experienced over interpersonal and intrapersonal pressures, and a decrease in the magnitude of control exerted on them by such pressures. The overall increase in the proportionate control experienced appeared to be accounted for by shifts made by those Ss who entered treatment with an initially internal locus of control."} {"id": "PMID:1262530", "title": "Isoproterenol sensitivity and total body clearance of propranolol in hypertensive patients.", "content": "The isoproterenol sensitivity (dose-response curve) and the total body clearance of propranolol were measured in 80 men including 15 normal subjects and 65 essential hypertensive patients (20 borderline and 45 permanent hypertensives). The critical dose of isoproterenol was found to be directly correlated to weight (P less than 0.01), age (P less than 0.001), and basal diastolic arterial pressure (P less than 0.001). A partial correlation coefficient study showed that the diastolic arterial pressure was of greater influence than weight and age. The total body clearance of propranolol was inversely related to the basal diastolic arterial pressure (P less than 0.0001) in hypertensive patients. The study provides evidence that the level of basal diastolic arterial pressure could influence the beta-receptor responsiveness and the beta-adrenergic blockade in hypertensive patients.", "contents": "Isoproterenol sensitivity and total body clearance of propranolol in hypertensive patients. The isoproterenol sensitivity (dose-response curve) and the total body clearance of propranolol were measured in 80 men including 15 normal subjects and 65 essential hypertensive patients (20 borderline and 45 permanent hypertensives). The critical dose of isoproterenol was found to be directly correlated to weight (P less than 0.01), age (P less than 0.001), and basal diastolic arterial pressure (P less than 0.001). A partial correlation coefficient study showed that the diastolic arterial pressure was of greater influence than weight and age. The total body clearance of propranolol was inversely related to the basal diastolic arterial pressure (P less than 0.0001) in hypertensive patients. The study provides evidence that the level of basal diastolic arterial pressure could influence the beta-receptor responsiveness and the beta-adrenergic blockade in hypertensive patients."} {"id": "PMID:1262531", "title": "Naproxen plasma levels in volunteers after single-dose administration by oral and rectal routes.", "content": "The bioavailability (plasma concentrations, AUC) of a rectal formulation (suppository) of naproxen was investigated in six healthy volunteers by comparison with an oral preparation (tablets). Plasma half-lives after both formulations were identical 10 hr 15 min+/-25 min (S.D.). Determined by the AUC the bioavailability of naproxen in the suppositories was 94.8%+/-6.3% of the bioavailability of naproxen in the tablets. This paper describes also a new gas-liquid chromatographic method for determining unchanged naproxen in human plasma which is quick, sensitive, and specific.", "contents": "Naproxen plasma levels in volunteers after single-dose administration by oral and rectal routes. The bioavailability (plasma concentrations, AUC) of a rectal formulation (suppository) of naproxen was investigated in six healthy volunteers by comparison with an oral preparation (tablets). Plasma half-lives after both formulations were identical 10 hr 15 min+/-25 min (S.D.). Determined by the AUC the bioavailability of naproxen in the suppositories was 94.8%+/-6.3% of the bioavailability of naproxen in the tablets. This paper describes also a new gas-liquid chromatographic method for determining unchanged naproxen in human plasma which is quick, sensitive, and specific."} {"id": "PMID:1262534", "title": "The clinical pharmacology of meperidine--comparison of routes of administration.", "content": "The serum time-concentration curves and pharmacokinetic parameters of meperidine after the intravenous, intramuscular, and oral administration of 26 mg/m2 doses were determined and compared. After 30 minutes, there was no statistically significant difference between the serum time-concentration curve following intravenous administration and intramuscular administration; and after 2 hours, all three serum time-concentration curves were the same. Comparison of the mean cumulative excretion of meperidine and normeperidine following all three routes of administration demonstrated that the maxmimun rates of both meperidine and normeperidine reflect the route of administration, with a marked delay following oral administration reflecting a delay in absorption. Further, the excretion of normeperidene following oral administration, is greater despite adequate absorption than the other two routes of administration, indicating that delayed absorption increases the metabolic phase. Subjective symptomatology and the serum time-concentration curves were compared and their relationship wxamined. Comparison of the serum time-concentration curves to pervious analgesic and toxicity trials was made, and minimum serum levels for induction of analgesia and production of side effects are discussed. From the data it appears that in the case of acute pain, the intramuscular route of administration is as beneficial as the intravenous route, that oral dosing is less efficacious due to lower peak serum concentrations, and that all doses, regardless of the route administration, should be administered clinically on a mg/m2 basis rather than as a predetermined dose as currently used. Oral administration may have some benefit in the treatment of chronic pain, but the possibility of cumulative toxicity due to normeperidine should be considered.", "contents": "The clinical pharmacology of meperidine--comparison of routes of administration. The serum time-concentration curves and pharmacokinetic parameters of meperidine after the intravenous, intramuscular, and oral administration of 26 mg/m2 doses were determined and compared. After 30 minutes, there was no statistically significant difference between the serum time-concentration curve following intravenous administration and intramuscular administration; and after 2 hours, all three serum time-concentration curves were the same. Comparison of the mean cumulative excretion of meperidine and normeperidine following all three routes of administration demonstrated that the maxmimun rates of both meperidine and normeperidine reflect the route of administration, with a marked delay following oral administration reflecting a delay in absorption. Further, the excretion of normeperidene following oral administration, is greater despite adequate absorption than the other two routes of administration, indicating that delayed absorption increases the metabolic phase. Subjective symptomatology and the serum time-concentration curves were compared and their relationship wxamined. Comparison of the serum time-concentration curves to pervious analgesic and toxicity trials was made, and minimum serum levels for induction of analgesia and production of side effects are discussed. From the data it appears that in the case of acute pain, the intramuscular route of administration is as beneficial as the intravenous route, that oral dosing is less efficacious due to lower peak serum concentrations, and that all doses, regardless of the route administration, should be administered clinically on a mg/m2 basis rather than as a predetermined dose as currently used. Oral administration may have some benefit in the treatment of chronic pain, but the possibility of cumulative toxicity due to normeperidine should be considered."} {"id": "PMID:1262538", "title": "Sustained-release lithium carbonate in double-blind study: serum lithium levels, side effects, and placebo response.", "content": "The utility and side effects of sustained-release lithium carbonate (Priadel) in a once-per-day dose regimen was investigated with 66 male delinquents, ages 17-24 years, in a double-blind study comparing the antiaggressive effect of lithium carbonate with placebo. Serum lithium levels and symptoms were determined weekly for up to eight drug-free and 12 on-medication weeks. Average daily doses of 1500-1700 mg Priadel gave 24-hour serum lithium levels in the range 0.7-0.9 mEq/liter. Principal side effects were polyuria and shakiness, with other important side effects bring hand tremor, dryness of mouth, nausea, and weakness. No lithium toxicity was observed, and diarrhea was reported infrequently. Placebo response data are presented.", "contents": "Sustained-release lithium carbonate in double-blind study: serum lithium levels, side effects, and placebo response. The utility and side effects of sustained-release lithium carbonate (Priadel) in a once-per-day dose regimen was investigated with 66 male delinquents, ages 17-24 years, in a double-blind study comparing the antiaggressive effect of lithium carbonate with placebo. Serum lithium levels and symptoms were determined weekly for up to eight drug-free and 12 on-medication weeks. Average daily doses of 1500-1700 mg Priadel gave 24-hour serum lithium levels in the range 0.7-0.9 mEq/liter. Principal side effects were polyuria and shakiness, with other important side effects bring hand tremor, dryness of mouth, nausea, and weakness. No lithium toxicity was observed, and diarrhea was reported infrequently. Placebo response data are presented."} {"id": "PMID:1262539", "title": "Autoradiographic studies of the projections of the midbrain reticular formation: ascending projections of nucleus cuneiformis.", "content": "The ascending projections of the cuneiform nucleus in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of (3)H-leucine. The ascending fibers are almost exclusively ipsilateral and enter the diencephalon as a wide radiation. At the mesodiencephalic junction fibers enter the nucleus of the posterior commissure and pretectal nuclei, and others cross in the posterior commissure to distribute to these structures on the contralateral side. More ventrally directed fibers distribute to the fields of Forel and then spread into the posterior hypothalamus and zona incerta. At the caudal level of the ventral thalamic group, the ascending fibers diverge and follow two separate courses. One division of fibers continues forward beneath the ventral thalamic group and distributes to the zpna incerta and dorsal hypothalamic area. It rapidly diminishes in size as it attains more rostral levels where it is found in the bed nuclei of the stria terminalis and the anterior commissure. Other fibers of this division spread laterally to innervate the ventral lateral geniculate nucleus, the lateral hypothalamus, and preoptic area, and still others follow the entire confirmation of the thalamic reticular nucleus. The second division of fiber ascends through midline and intralaminar nuclei, completely encircling the mediodorsal nucleus, which is uninnervated except for a small ventral region. The distribution of this division is heaviest to the paraventricular, parafascicular, and central dorsal nuclei. Neither division is conspicuous rostral to the anterior commissure. No projections to neostriatum or specific thalamic nuclei were evident.", "contents": "Autoradiographic studies of the projections of the midbrain reticular formation: ascending projections of nucleus cuneiformis. The ascending projections of the cuneiform nucleus in the cat were traced by autoradiography in the transverse and sagittal planes following stereotaxically placed injections of (3)H-leucine. The ascending fibers are almost exclusively ipsilateral and enter the diencephalon as a wide radiation. At the mesodiencephalic junction fibers enter the nucleus of the posterior commissure and pretectal nuclei, and others cross in the posterior commissure to distribute to these structures on the contralateral side. More ventrally directed fibers distribute to the fields of Forel and then spread into the posterior hypothalamus and zona incerta. At the caudal level of the ventral thalamic group, the ascending fibers diverge and follow two separate courses. One division of fibers continues forward beneath the ventral thalamic group and distributes to the zpna incerta and dorsal hypothalamic area. It rapidly diminishes in size as it attains more rostral levels where it is found in the bed nuclei of the stria terminalis and the anterior commissure. Other fibers of this division spread laterally to innervate the ventral lateral geniculate nucleus, the lateral hypothalamus, and preoptic area, and still others follow the entire confirmation of the thalamic reticular nucleus. The second division of fiber ascends through midline and intralaminar nuclei, completely encircling the mediodorsal nucleus, which is uninnervated except for a small ventral region. The distribution of this division is heaviest to the paraventricular, parafascicular, and central dorsal nuclei. Neither division is conspicuous rostral to the anterior commissure. No projections to neostriatum or specific thalamic nuclei were evident."} {"id": "PMID:1262536", "title": "Failure of vitamin C to affect the pharmacokinetic profile of antipyrine in man.", "content": "A possible interaction of vitamin C with the metabolism of drugs which are oxidized (e.g., antipyrine and diphenylhydantion) is indicated from data in animals. The effect of megadoses of vitamin C (300 mg/day to 4800 mg/day) was therefore tested in human volunteers receiving antiprine (single oral dose) or diphenlhydantoin (chronic therapy). The half-life, volume of distribution, and plasma clearance of antipyrine were not affected by vitamin C treatment. Steady-state plasma levels of diphenylhydantoin in two epileptic patients were similar before and during vitamin C (1.2 Gm/day for 18 days) treatment. It is concluded that vitamin C, in commonly used megadoses, has no effect on the metabolism of antipyrine or diphenylhydantoin in men.", "contents": "Failure of vitamin C to affect the pharmacokinetic profile of antipyrine in man. A possible interaction of vitamin C with the metabolism of drugs which are oxidized (e.g., antipyrine and diphenylhydantion) is indicated from data in animals. The effect of megadoses of vitamin C (300 mg/day to 4800 mg/day) was therefore tested in human volunteers receiving antiprine (single oral dose) or diphenlhydantoin (chronic therapy). The half-life, volume of distribution, and plasma clearance of antipyrine were not affected by vitamin C treatment. Steady-state plasma levels of diphenylhydantoin in two epileptic patients were similar before and during vitamin C (1.2 Gm/day for 18 days) treatment. It is concluded that vitamin C, in commonly used megadoses, has no effect on the metabolism of antipyrine or diphenylhydantoin in men."} {"id": "PMID:1262540", "title": "Central control of song in the canary, Serinus canarius.", "content": "We have traced central nervous pathways controlling bird song in the canary using a combination of behavioral and anatomical techniques. Unilateral electrolytic brain lesions were made in adult male canaries whose song had been previously recorded and analysed on a sound spectrograph. After several days of postoperative recording, the birds were sacrificed and their brains processed histologically for degeneration staining with the Fink-Heimer technique. Although large lesions in the neostriatum and rostral hyperstriatum had no effect on song, severe song deficits followed damage to a discrete large-celled area in the caudal hyperstriatum ventrale (HVc). Degenerating fibers were traced from this region to two other discrete nuclei in the forebrain: one in the parolfactory lobe (area X, a teardrop-shaped small-celled nucleus); and a round large-celled nucleus in the archistriatum (RA). Unilateral lesion of X had no effect on song; lesions of RA, however, caused severe song deficits. Degenerating fibers from RA joined the occipitomesencephalic tract and had widespread ipsilateral projections to the thalamus, nucleus intercollicularis of the midbrain, reticular formation, and medulla. It is of particular interest that direct connections were found onto the cells of the motor nucleus innervating the syrinx, the organ of song production. Unilateral lesions of n. intercollicularis (previously implicated in the control of vocal behavior) had little effect on song. One bilateral lesion of HVc resulted in permanent (9 months) and complete elimination of the audible components of song, although the bird assumed the posture and movements typical of song. Preliminary data suggest that lesions of the left hemisphere result in greater deficits than lesions of the right one. This finding is consistent with earlier reports that the left syrinx controls the majority of song components. Results reported here suggest a localization of vocal control in the canary brain with an overlying left hemispheric dominance.", "contents": "Central control of song in the canary, Serinus canarius. We have traced central nervous pathways controlling bird song in the canary using a combination of behavioral and anatomical techniques. Unilateral electrolytic brain lesions were made in adult male canaries whose song had been previously recorded and analysed on a sound spectrograph. After several days of postoperative recording, the birds were sacrificed and their brains processed histologically for degeneration staining with the Fink-Heimer technique. Although large lesions in the neostriatum and rostral hyperstriatum had no effect on song, severe song deficits followed damage to a discrete large-celled area in the caudal hyperstriatum ventrale (HVc). Degenerating fibers were traced from this region to two other discrete nuclei in the forebrain: one in the parolfactory lobe (area X, a teardrop-shaped small-celled nucleus); and a round large-celled nucleus in the archistriatum (RA). Unilateral lesion of X had no effect on song; lesions of RA, however, caused severe song deficits. Degenerating fibers from RA joined the occipitomesencephalic tract and had widespread ipsilateral projections to the thalamus, nucleus intercollicularis of the midbrain, reticular formation, and medulla. It is of particular interest that direct connections were found onto the cells of the motor nucleus innervating the syrinx, the organ of song production. Unilateral lesions of n. intercollicularis (previously implicated in the control of vocal behavior) had little effect on song. One bilateral lesion of HVc resulted in permanent (9 months) and complete elimination of the audible components of song, although the bird assumed the posture and movements typical of song. Preliminary data suggest that lesions of the left hemisphere result in greater deficits than lesions of the right one. This finding is consistent with earlier reports that the left syrinx controls the majority of song components. Results reported here suggest a localization of vocal control in the canary brain with an overlying left hemispheric dominance."} {"id": "PMID:1262541", "title": "Hormone concentrating cells in vocal control and other areas of the brain of the zebra finch ( Poephila guttata).", "content": "Using the autoradiographic method in the zebra finch (poephila guttata), areas of the brain were identified which contain cells which accumulate testosterone. Among these areas are the caudal nucleus of the hyperstriatum ventrale, nucleus intercollicularis of the midbrain, and the tracheosyringeal portion of the hypoglossal nucleus of the medulla (nXIIts). These three are known to control or influence androgen dependent song and other vocalizations of passeriform birds, and nXIIts is composed of the motoneurons innervating the vocal (syringeal) muscles. Other areas containing hormone-concentrating cells are the medial preoptic area, nucleus periventricularis magnocellularis of the hypothalamus, dorsal infundibular layers, dorsomedial thalamus, lateral septum, magnocellular nucleus of the anterior neostriatum, periventricular medial neostriatum, nucleus taeniae of the archistriatum, and ventral paleostriatum augmentatum. Accumulation by cells in the preoptic area, hypothalamus, and limbic forebrain is consistent with a general vertebrate pattern of distribution of brain cells which accumulate sex steroids. Some of these same areas may be involved in the control of androgen dependent events such as courtship, copulation, aggression, and feedback regulation of the hypophysis.", "contents": "Hormone concentrating cells in vocal control and other areas of the brain of the zebra finch ( Poephila guttata). Using the autoradiographic method in the zebra finch (poephila guttata), areas of the brain were identified which contain cells which accumulate testosterone. Among these areas are the caudal nucleus of the hyperstriatum ventrale, nucleus intercollicularis of the midbrain, and the tracheosyringeal portion of the hypoglossal nucleus of the medulla (nXIIts). These three are known to control or influence androgen dependent song and other vocalizations of passeriform birds, and nXIIts is composed of the motoneurons innervating the vocal (syringeal) muscles. Other areas containing hormone-concentrating cells are the medial preoptic area, nucleus periventricularis magnocellularis of the hypothalamus, dorsal infundibular layers, dorsomedial thalamus, lateral septum, magnocellular nucleus of the anterior neostriatum, periventricular medial neostriatum, nucleus taeniae of the archistriatum, and ventral paleostriatum augmentatum. Accumulation by cells in the preoptic area, hypothalamus, and limbic forebrain is consistent with a general vertebrate pattern of distribution of brain cells which accumulate sex steroids. Some of these same areas may be involved in the control of androgen dependent events such as courtship, copulation, aggression, and feedback regulation of the hypophysis."} {"id": "PMID:1262537", "title": "Effects on visual tracking of delta9-tetrahydrocannabinol and pentobarbital.", "content": "Detal-9-tetrahydrocannabinol and pentobarbital both interfered with visual tracking performance. Of these, delta9THC had a statistically significant effect (P less than 0.04) when the first 12 responses for each subject were analyzed at each half-hourly period.", "contents": "Effects on visual tracking of delta9-tetrahydrocannabinol and pentobarbital. Detal-9-tetrahydrocannabinol and pentobarbital both interfered with visual tracking performance. Of these, delta9THC had a statistically significant effect (P less than 0.04) when the first 12 responses for each subject were analyzed at each half-hourly period."} {"id": "PMID:1262542", "title": "Gustatory pathways in the bullhead catfish. 1. Connections of the anterior ganglion.", "content": "The central projections of the external gustatory system in bullhead catfish were examined using orthograde degeneration and retrograde transport of horseradish peroxidase (HRP) techniques. Both large and small cells were observed in the anterior ganglion which contains a mixture of elements from the trigeminal, facial and anterior lateral line nerves. Some of the large cells on the lateral margin of the ganglion were found to belong to the lateral line system. No separation of trigeminal and facial nerve connections could be made. Using HRP, the relation between the barbels and specific ganglion regions was determined. The dorsalmost portion of the ganglion received recurrens nerve inputs (from taste buds on the trunk); the rostromedial portion of the ganglion, from the maxillary and mandibular barbel nerves. The facial lobe (similar to part of the n. solitarius) was found to be divided into lobules by fascicles of nerve fibers. The lateral lobule received input only from the dorsal-most part of the ganglion (recurrens nerve: trunk receptors); the intermediate lobule from the rostro-lateral part of the ganglion (nasal barbel); and the medial lobule from the ventral areas of the ganglion (maxillary and mandibular barbels). Thus a topographical relationship exists between the different taste receptor groups and their locus of representation in the facial lobe. The trunk receptors connect to the lateral lobule; the nasal barbel receptors to the intermediate lobule, and the maxillo-mandibular receptors to the medial lobule.", "contents": "Gustatory pathways in the bullhead catfish. 1. Connections of the anterior ganglion. The central projections of the external gustatory system in bullhead catfish were examined using orthograde degeneration and retrograde transport of horseradish peroxidase (HRP) techniques. Both large and small cells were observed in the anterior ganglion which contains a mixture of elements from the trigeminal, facial and anterior lateral line nerves. Some of the large cells on the lateral margin of the ganglion were found to belong to the lateral line system. No separation of trigeminal and facial nerve connections could be made. Using HRP, the relation between the barbels and specific ganglion regions was determined. The dorsalmost portion of the ganglion received recurrens nerve inputs (from taste buds on the trunk); the rostromedial portion of the ganglion, from the maxillary and mandibular barbel nerves. The facial lobe (similar to part of the n. solitarius) was found to be divided into lobules by fascicles of nerve fibers. The lateral lobule received input only from the dorsal-most part of the ganglion (recurrens nerve: trunk receptors); the intermediate lobule from the rostro-lateral part of the ganglion (nasal barbel); and the medial lobule from the ventral areas of the ganglion (maxillary and mandibular barbels). Thus a topographical relationship exists between the different taste receptor groups and their locus of representation in the facial lobe. The trunk receptors connect to the lateral lobule; the nasal barbel receptors to the intermediate lobule, and the maxillo-mandibular receptors to the medial lobule."} {"id": "PMID:1262543", "title": "Retinofugal pathways in the lingnose gar Lepisosteus osseus (linnaeus).", "content": "Retinal projections were studied with autoradiographic and silver methods in the gar, Lepisosteus osseus, one of the two surviving members of the holostean actinopterygians. Contralaterally, the retina projects to the preoptic nucleus of the hypothalamus, and, via the medial optic tract, to the dorsal thalamus, medial ventral thalamic nucleus, nucleus pretectalis profundus pars ventralis and pars dorsalis, and the medial portion of the deep layers of the central zone in the optic tectum. The dorsal optic tract projects to the lateral ventral thalamic nucleus, nucleus pretectalis centralis, and the superficial white and gray zone of the optic tectum. The ventral optic tract terminates in the nucleus of the ventral optic tract, the lateral and medial ventral thalamic nuclei, nucleus pretectalis superficialis, nucleus pretectalis centralis, nucleus pretectalis profundus pars ventralis, the basal optic nucleus, and the superficial white and gray zone of the optic tectum. Ipsilateral projections are to similar sites, except for an absence of inputs to the lateral ventral thalamic nucleus from the dorsal tract and to the nucleus pretectalis superficialis, nucleus pretectalis profundus pars ventralis, and the basal optic nucleus from the ventral tract. The presence of ipsilateral retinal projections in gars is compared to their presumed absence in teleosts, and comparisons of retinorecipient targets in gars are made with teleosts and with non-actinopterygian vertebrates.", "contents": "Retinofugal pathways in the lingnose gar Lepisosteus osseus (linnaeus). Retinal projections were studied with autoradiographic and silver methods in the gar, Lepisosteus osseus, one of the two surviving members of the holostean actinopterygians. Contralaterally, the retina projects to the preoptic nucleus of the hypothalamus, and, via the medial optic tract, to the dorsal thalamus, medial ventral thalamic nucleus, nucleus pretectalis profundus pars ventralis and pars dorsalis, and the medial portion of the deep layers of the central zone in the optic tectum. The dorsal optic tract projects to the lateral ventral thalamic nucleus, nucleus pretectalis centralis, and the superficial white and gray zone of the optic tectum. The ventral optic tract terminates in the nucleus of the ventral optic tract, the lateral and medial ventral thalamic nuclei, nucleus pretectalis superficialis, nucleus pretectalis centralis, nucleus pretectalis profundus pars ventralis, the basal optic nucleus, and the superficial white and gray zone of the optic tectum. Ipsilateral projections are to similar sites, except for an absence of inputs to the lateral ventral thalamic nucleus from the dorsal tract and to the nucleus pretectalis superficialis, nucleus pretectalis profundus pars ventralis, and the basal optic nucleus from the ventral tract. The presence of ipsilateral retinal projections in gars is compared to their presumed absence in teleosts, and comparisons of retinorecipient targets in gars are made with teleosts and with non-actinopterygian vertebrates."} {"id": "PMID:1262544", "title": "An experimental inquiry into the central source of preganglionic fibers to the chick ciliary ganglion.", "content": "Degenerative changes in the entire third nerve nucleus were studied following selective removal of the ciliary ganglion, usually of the right side, in day-old chicks. The operated animals were allowed to survive three, six, nine, and twelve days after ciliary ganglionectomy. Retrogarde degenerative changes proceed rapidly between three and nine days post-operatively, and are strictly limited to the ipsilateral accessory oculomotor nucleus. The changes are at first observed in the medial division of the accessory oculomotor nucleus, followed by the lateral division of the accessory oculomotor nucleus. By nine days following the operation, both the divisions of the accessory oculomotor nucleus are virtually depleted of almost all neurons. The other components of the oculomotor complex were not affected at any stage by ciliary ganglionectomy. These observations provide conclusive evidence that the accessory oculomotor nucleus is indeed the avian homologue of the Edinger-Westphal nucleus.", "contents": "An experimental inquiry into the central source of preganglionic fibers to the chick ciliary ganglion. Degenerative changes in the entire third nerve nucleus were studied following selective removal of the ciliary ganglion, usually of the right side, in day-old chicks. The operated animals were allowed to survive three, six, nine, and twelve days after ciliary ganglionectomy. Retrogarde degenerative changes proceed rapidly between three and nine days post-operatively, and are strictly limited to the ipsilateral accessory oculomotor nucleus. The changes are at first observed in the medial division of the accessory oculomotor nucleus, followed by the lateral division of the accessory oculomotor nucleus. By nine days following the operation, both the divisions of the accessory oculomotor nucleus are virtually depleted of almost all neurons. The other components of the oculomotor complex were not affected at any stage by ciliary ganglionectomy. These observations provide conclusive evidence that the accessory oculomotor nucleus is indeed the avian homologue of the Edinger-Westphal nucleus."} {"id": "PMID:1262545", "title": "Functional role of efferents to the avian retina. I. Analysis of retinal ganglion cell receptive fields.", "content": "Receptive fields of retinal ganglion cells were analyzed during extracellular microelectrode recordings in the optic tract of the lightly anesthetized pigeon. Four major types of receptive field can be distinguished among the 359 fibers studied. Twenty-five percent of the receptive fields are relatively simple, responding at on and at off to stationary spots of light in the central region. All of the receptive fields have inhibitory surrounds of varying strength that do not produce a response when illuminated alone, but antagonize responses from the central region. Motion sensitive units comprise 15% of the recorded population; they are similar to the on-off center type except that responses to stationary stimuli are absent or very weak while responses to moving stimuli are virorous. Directionally selective units also have the basic features of on-off, inhibitory surround cells, but respond to moving stimuli well from the preferred direction and not at all from the null direction. Directional cells have a broad range of null directions; in about one-third of the units the range becomes broader when the stimulus involves both center and surround of the receptive field, thus enhancing directional selectivity. Directionally selective units are common, comprising 38% of the units studied. Cells unresponsive to stimuli moving from anterior in the visual field are much more common than other types, while cells unresponsive to stimuli from posterior in the field are rare. A few units (11%) respond only at on or at off to stationary stimuli in their receptive field centers; they also have antagonistic but unresponsive receptive field surrounds. The area of the visual field sampled is uniform in regard to the relative numbers of the four major receptive field types.", "contents": "Functional role of efferents to the avian retina. I. Analysis of retinal ganglion cell receptive fields. Receptive fields of retinal ganglion cells were analyzed during extracellular microelectrode recordings in the optic tract of the lightly anesthetized pigeon. Four major types of receptive field can be distinguished among the 359 fibers studied. Twenty-five percent of the receptive fields are relatively simple, responding at on and at off to stationary spots of light in the central region. All of the receptive fields have inhibitory surrounds of varying strength that do not produce a response when illuminated alone, but antagonize responses from the central region. Motion sensitive units comprise 15% of the recorded population; they are similar to the on-off center type except that responses to stationary stimuli are absent or very weak while responses to moving stimuli are virorous. Directionally selective units also have the basic features of on-off, inhibitory surround cells, but respond to moving stimuli well from the preferred direction and not at all from the null direction. Directional cells have a broad range of null directions; in about one-third of the units the range becomes broader when the stimulus involves both center and surround of the receptive field, thus enhancing directional selectivity. Directionally selective units are common, comprising 38% of the units studied. Cells unresponsive to stimuli moving from anterior in the visual field are much more common than other types, while cells unresponsive to stimuli from posterior in the field are rare. A few units (11%) respond only at on or at off to stationary stimuli in their receptive field centers; they also have antagonistic but unresponsive receptive field surrounds. The area of the visual field sampled is uniform in regard to the relative numbers of the four major receptive field types."} {"id": "PMID:1262546", "title": "Functional role of efferents to the avian retina. II. Effects of reversible cooling of the isthmo-optic nucleus.", "content": "Efferents to the retina in the bird arise in the isthmo-optic nucleus of the caudal midbrain, and terminate on amacrine cells in the retina. The functional role of these efferents was studied by determining the receptive field properties of 107 optic tract fibers in the lightly anesthetized adult pigeon, and quantitating their responses to specific moving stimuli. While the recording from these fibers continued, the isthmo-optic nucleus was cooled by a thermoelectric cooling probe, and the response properties of the cells redetermined. Recording was maintained in half of the units long enough to observe recovery from cooling, and in several units the entire procedure was repeated. In 77 of the 107 units, responsiveness to all stimuli was decreased by removing efferent influences, whereas specific receptive field properties such as motion sensitivity or directionaltiy were not altered. All of the major receptive field types were affected in a similar fashion, irrespective of their position in the visual field. Responses to stimuli that did not involve the antagonistic surround were similarly affected by removal of the efferents, as were units were both weak and strong antagonistic surrounds. Efferents exert their influence on retinal ganglion cells by way of the amacrine cells on which they terminate. Data available on amacrines in Necturus indicates that they are inhibitory to ganglion cells. If amacrines have a similar role in the pigeon, then it may be stated that decreased activity in the centrifugal fibers leads to enhanced inhibition throughout the receptive fields of ganglion cells, and increased activity in the efferents produces disinhibition.", "contents": "Functional role of efferents to the avian retina. II. Effects of reversible cooling of the isthmo-optic nucleus. Efferents to the retina in the bird arise in the isthmo-optic nucleus of the caudal midbrain, and terminate on amacrine cells in the retina. The functional role of these efferents was studied by determining the receptive field properties of 107 optic tract fibers in the lightly anesthetized adult pigeon, and quantitating their responses to specific moving stimuli. While the recording from these fibers continued, the isthmo-optic nucleus was cooled by a thermoelectric cooling probe, and the response properties of the cells redetermined. Recording was maintained in half of the units long enough to observe recovery from cooling, and in several units the entire procedure was repeated. In 77 of the 107 units, responsiveness to all stimuli was decreased by removing efferent influences, whereas specific receptive field properties such as motion sensitivity or directionaltiy were not altered. All of the major receptive field types were affected in a similar fashion, irrespective of their position in the visual field. Responses to stimuli that did not involve the antagonistic surround were similarly affected by removal of the efferents, as were units were both weak and strong antagonistic surrounds. Efferents exert their influence on retinal ganglion cells by way of the amacrine cells on which they terminate. Data available on amacrines in Necturus indicates that they are inhibitory to ganglion cells. If amacrines have a similar role in the pigeon, then it may be stated that decreased activity in the centrifugal fibers leads to enhanced inhibition throughout the receptive fields of ganglion cells, and increased activity in the efferents produces disinhibition."} {"id": "PMID:1262547", "title": "Taste pathways to hypothalamus and amygdala.", "content": "The projections of a third order gustatory relay in the dorsal pons of rats have been traced using tritiated proline autoradiography and antidromic activation of pontine neurons from electrodes in the thalamus and amygdala. Labelled axons collect in the central tegmental tract and ascend to the thalamic taste area in the medial extension of the ventrobasal complex. The majority of the fibers remain ipsilateral, but a few cross in the rostral pons and midbrain. The largest crossing occurs at the level of the thalamic termination. Many fascicles of fibers continue rostrally by passing beneath the thalamic taste area, piercing the medial lemniscus, and spreading out along the dorsomedial corner of the internal capsule (IC). The terminal field at this level caps IC from the subthalamic nucleus down into the far-lateral hypothalamus. Labelled axons grandually penetrate through the internal capsule, and ramify throughout the underlying substantia innominata. This terminal zone extends laterally into the rostral end of the central nucleus of the amygdala, which is densely labelled to its caudal exremity. At the caudal end of the amygdala labelled fibers are visible in one component of the stria terminalis. These fibers can be followed over the dorsal thalamus into a smaller, but equally dense terminal area in the dorsolateral bed nucleus of the stria terminalis. The electrophysiological data demonstrate that pontine gustatory units can be antidromically activated by electrodes located in or near the central nucleus of the amygdala. Since many of the same units can also be driven from the thalamic taste area, at least some of the axons traced autoradiographically probably convey gustatory information to the hypothalamus and amygdala.", "contents": "Taste pathways to hypothalamus and amygdala. The projections of a third order gustatory relay in the dorsal pons of rats have been traced using tritiated proline autoradiography and antidromic activation of pontine neurons from electrodes in the thalamus and amygdala. Labelled axons collect in the central tegmental tract and ascend to the thalamic taste area in the medial extension of the ventrobasal complex. The majority of the fibers remain ipsilateral, but a few cross in the rostral pons and midbrain. The largest crossing occurs at the level of the thalamic termination. Many fascicles of fibers continue rostrally by passing beneath the thalamic taste area, piercing the medial lemniscus, and spreading out along the dorsomedial corner of the internal capsule (IC). The terminal field at this level caps IC from the subthalamic nucleus down into the far-lateral hypothalamus. Labelled axons grandually penetrate through the internal capsule, and ramify throughout the underlying substantia innominata. This terminal zone extends laterally into the rostral end of the central nucleus of the amygdala, which is densely labelled to its caudal exremity. At the caudal end of the amygdala labelled fibers are visible in one component of the stria terminalis. These fibers can be followed over the dorsal thalamus into a smaller, but equally dense terminal area in the dorsolateral bed nucleus of the stria terminalis. The electrophysiological data demonstrate that pontine gustatory units can be antidromically activated by electrodes located in or near the central nucleus of the amygdala. Since many of the same units can also be driven from the thalamic taste area, at least some of the axons traced autoradiographically probably convey gustatory information to the hypothalamus and amygdala."} {"id": "PMID:1262548", "title": "Fiber trajectories of olfactory bulb efferents in the hamster.", "content": "Olfactory bulb efferents sweep caudally over the surface of the piriform lobe in a broad fiber sheet. The internal organization of this axon population was analysed by topologically transforming the cortical surface from its in situ cylindrical form into an unrolled (flattened) map. The distribution of degeneration elicited by restricted bulb lesions and fiber transections was then reconstructed onto this map. Most of the projection cortex of the main olfactory bulb is innervated in a widespread, non-topographic manner by axons that collect in the compact bundle of the lateral olfactory tract (LOT). LOT collateral branches bound for the prepiriform cortex veer laterally off the main trajectory of the tract at an angle of 50 degrees or less. Thus, transection of discrete fiber populations leaves only a small wedge-shaped pocket of totally denervated cortex distal to the cut. The medial half of the olfactory tubercle and the hippocampal rudiment receive their bulbar input along medially disposed fibers that do not join the LOT proper. The lateral half of the olfactory tubercle, however, receives an input from LOT fiber collaterals as well as these medial bulb efferents. Finally, much of the corticomedial amygdaloid complex receives fibers from the accessory olfactory bulb along a specialized subdivision of the LOT, the accessory olfactory tract. These observations are expressed in a schematic summary of the trajectories of olfactory bulb efferents as they appear in the unrolled map and in the more standard ventral view of the hamster brain.", "contents": "Fiber trajectories of olfactory bulb efferents in the hamster. Olfactory bulb efferents sweep caudally over the surface of the piriform lobe in a broad fiber sheet. The internal organization of this axon population was analysed by topologically transforming the cortical surface from its in situ cylindrical form into an unrolled (flattened) map. The distribution of degeneration elicited by restricted bulb lesions and fiber transections was then reconstructed onto this map. Most of the projection cortex of the main olfactory bulb is innervated in a widespread, non-topographic manner by axons that collect in the compact bundle of the lateral olfactory tract (LOT). LOT collateral branches bound for the prepiriform cortex veer laterally off the main trajectory of the tract at an angle of 50 degrees or less. Thus, transection of discrete fiber populations leaves only a small wedge-shaped pocket of totally denervated cortex distal to the cut. The medial half of the olfactory tubercle and the hippocampal rudiment receive their bulbar input along medially disposed fibers that do not join the LOT proper. The lateral half of the olfactory tubercle, however, receives an input from LOT fiber collaterals as well as these medial bulb efferents. Finally, much of the corticomedial amygdaloid complex receives fibers from the accessory olfactory bulb along a specialized subdivision of the LOT, the accessory olfactory tract. These observations are expressed in a schematic summary of the trajectories of olfactory bulb efferents as they appear in the unrolled map and in the more standard ventral view of the hamster brain."} {"id": "PMID:1262549", "title": "Neuroplasticity in the rearrangement of olfactory tract fibers after neonatal transection in hamsters.", "content": "Olfactory bulb efferent axons run caudally in the lateral olfactory tract (LOT) to end in a broad cortical field in the ventral forebrain. Principles governing the plastic rearrangement of this fiber population after early lesions were probed by cutting the tract in hamster pups and studying the distribution of surviving olfactory bulb projections in adulthood using silver and autoradiographic techniques. The spatial pattern of rearrangement proved to depend on the extent of the cut and also the age at which it was made. For example, after complete LOT section at seven days of age no bulb efferents appeared distal to the cut but the proximal projection increased in laminar thickness and spread laterally and medially beyond its normal cytoarchitectonic boundaries. This spread was less pronounced in animals with earlier or later lesions. After transection of only part of the LOT fibers at seven days of age the proximal input was similarly increased. Just distal to the transection, uncut fibers sprouted collaterals to fill the terminal sites vacated as a result of the lesion. In these cases, however, the farthest distal parts of the projection field lost their normal innervation. In a tentative interpretation of these data it is proposed that developing LOT fibers tend to conserve their total amount of axonal arbor. That is, when distal branches are pruned off surgically, the axon compensates by producing extra proximal branches. When an overabundance of proximal collaterals are produced in axons that have not been surgically pruned the growth of more distal axonal branches is stunted in compensation.", "contents": "Neuroplasticity in the rearrangement of olfactory tract fibers after neonatal transection in hamsters. Olfactory bulb efferent axons run caudally in the lateral olfactory tract (LOT) to end in a broad cortical field in the ventral forebrain. Principles governing the plastic rearrangement of this fiber population after early lesions were probed by cutting the tract in hamster pups and studying the distribution of surviving olfactory bulb projections in adulthood using silver and autoradiographic techniques. The spatial pattern of rearrangement proved to depend on the extent of the cut and also the age at which it was made. For example, after complete LOT section at seven days of age no bulb efferents appeared distal to the cut but the proximal projection increased in laminar thickness and spread laterally and medially beyond its normal cytoarchitectonic boundaries. This spread was less pronounced in animals with earlier or later lesions. After transection of only part of the LOT fibers at seven days of age the proximal input was similarly increased. Just distal to the transection, uncut fibers sprouted collaterals to fill the terminal sites vacated as a result of the lesion. In these cases, however, the farthest distal parts of the projection field lost their normal innervation. In a tentative interpretation of these data it is proposed that developing LOT fibers tend to conserve their total amount of axonal arbor. That is, when distal branches are pruned off surgically, the axon compensates by producing extra proximal branches. When an overabundance of proximal collaterals are produced in axons that have not been surgically pruned the growth of more distal axonal branches is stunted in compensation."} {"id": "PMID:1262550", "title": "Synapses in the interpeduncular nucleus: electron microscopy of normal and habenula lesioned rats.", "content": "Four types of synapses have been identified in the rat interpeduncular nucleus. The S synapses were formed by the mainhorizontal plexus of habenulointerpeduncular axons. They contained spherical synaptic vesicles and formed asymmetrical en passant contacts with dendritic processes. The crest synapses had all of these features in common with the S synapses, but occurred in pairs with the two contact zones coextensive and largely parallel on opposite sides of markedly attenuated dendritic processes. Synaptic glomeruli found in this nucleus consisted of several crest synapses engulfed by sheet-like dendritic processes. Identical crest synapses also occurred on dendritic crests. In a limited number of cases, both S and crest synapses arose in common from single axons. Following destruction of the habenular nuclei unilaterally or bilaterally, as expected from the above observations, both S and crest synapses underwent dense degeneration. In some cases with bilateral lesions and in all cases with unilateral lesions, only one of the two axonal endings forming a crest synapse degenerated while the other remained unaffected. Axons containing flat vesicles forming symmetrical axodendritic synapses, axosomatic synapses, and subjunctional bodies associated with S or crest synapses were all minor features of this nucleus. Aspects of the unusual synaptology of this nucleus are discussed in terms of morphology, physiology and transmitter chemistry.", "contents": "Synapses in the interpeduncular nucleus: electron microscopy of normal and habenula lesioned rats. Four types of synapses have been identified in the rat interpeduncular nucleus. The S synapses were formed by the mainhorizontal plexus of habenulointerpeduncular axons. They contained spherical synaptic vesicles and formed asymmetrical en passant contacts with dendritic processes. The crest synapses had all of these features in common with the S synapses, but occurred in pairs with the two contact zones coextensive and largely parallel on opposite sides of markedly attenuated dendritic processes. Synaptic glomeruli found in this nucleus consisted of several crest synapses engulfed by sheet-like dendritic processes. Identical crest synapses also occurred on dendritic crests. In a limited number of cases, both S and crest synapses arose in common from single axons. Following destruction of the habenular nuclei unilaterally or bilaterally, as expected from the above observations, both S and crest synapses underwent dense degeneration. In some cases with bilateral lesions and in all cases with unilateral lesions, only one of the two axonal endings forming a crest synapse degenerated while the other remained unaffected. Axons containing flat vesicles forming symmetrical axodendritic synapses, axosomatic synapses, and subjunctional bodies associated with S or crest synapses were all minor features of this nucleus. Aspects of the unusual synaptology of this nucleus are discussed in terms of morphology, physiology and transmitter chemistry."} {"id": "PMID:1262551", "title": "Organization of retinocollicular pathways in the cat.", "content": "A direct pathway from the temporal retina to the contralateral superior colliculus has been demonstrated using anterograde degeneration methods. This observation of a crossed pathway to the most rostral pole of the colliculus confirms electrophysiological evidence that within each colliculus the whole eye, rather than just its hemiretina is represented. Autoradiographic tracing methods have been used to study the total tectal projection of each retina. Following intreocular injections of 3H proline, there is dense label in most of the superficial gray of the contralateral colliculus, but in this region there are several small areas of only relatively sparse label. In contrast, the superficial gray of the ipsilateral colliculus contains islands or patches of transported label. These patches are present throughout an extensive region of the colliculus and suggest that the ipsilateral retinocollicular pathway in the cat may be more substantial than earlier reports have indicated. There is no ipsilateral label within the most caudal parts of the colliculus which receives afferents from the monocular crescent of the rostral pole is free of ipsilateral input, and we suggest that this corresponds to the region receiving the crossed input from the temporal retina.", "contents": "Organization of retinocollicular pathways in the cat. A direct pathway from the temporal retina to the contralateral superior colliculus has been demonstrated using anterograde degeneration methods. This observation of a crossed pathway to the most rostral pole of the colliculus confirms electrophysiological evidence that within each colliculus the whole eye, rather than just its hemiretina is represented. Autoradiographic tracing methods have been used to study the total tectal projection of each retina. Following intreocular injections of 3H proline, there is dense label in most of the superficial gray of the contralateral colliculus, but in this region there are several small areas of only relatively sparse label. In contrast, the superficial gray of the ipsilateral colliculus contains islands or patches of transported label. These patches are present throughout an extensive region of the colliculus and suggest that the ipsilateral retinocollicular pathway in the cat may be more substantial than earlier reports have indicated. There is no ipsilateral label within the most caudal parts of the colliculus which receives afferents from the monocular crescent of the rostral pole is free of ipsilateral input, and we suggest that this corresponds to the region receiving the crossed input from the temporal retina."} {"id": "PMID:1262552", "title": "Increases in collateral axonal growth rostral to a thoracic hemisection in neonatal and weanling rat.", "content": "The spinal cords of newborn and weanling rats were hemisected at the mid-thoracic level. Control studies revealed that Fink-Heimer positive debris was absent in the gray matter at three months postoperative. The remaining animals were given a second lesion, a high cervical spinal hemisection, at five to seven months after the original thoracic hemisection. The pattern of degeneration rostal to the thoracic lesion was compared with similar regions of the spinal cord from animals receiving only a cervical hemisection at the adult stage. In neither experimental group of doubly hemisected rats was there any degeneration observed below the thoracic lesion site, even though no glial or connective tissue scar had formed in animals originally operated at birth. Thus no regeneration had occurred. At least one segment above the initial hemisection: 1. the majority of degenerating axons were localized toward the lateral edge of the spinal cord, especially in the doubly lesioned neonatal group; 2. the erae of ipsilateral white matter was reduced more in the neonatal than the weanling operates; 3. there was an upward shift in axonal diameter of ipsilateral fibers in both the region of the rubrospinal tract and the ventrolateral portion of the lateral funiculus of the doubly hemisected rats when compared with the cervically lesioned controls; 4. a significantly greater amount of degeneration was present in lamina VII of Rexed in both the neonatal and weanling experimental operates (p less than 0.05 weanling; p less than 0.001 neonate); 5. no mean difference in area was seen between the ipsilateral and contralateral gray matter in any group for the segments of the spinal cord in which the judgements and measurements were taken. These data suggest that there has been sprouting of axons from descending nerve tracts rostral to the thoracic lesion in both the neonatal and weanling experimental groups. The question remains whether the sprouting of descending nerve tracts is from collateral of axons which normally project rostral to the thoracic hemisection and are not cut by the thoracic lesion (collateral sprouting) or from collaterals of lesioned axons (regenerative sprouting). Present evidence favors collateral sprouting, expecially in the neonatal operate where much retrograde cell death appears to have taken place.", "contents": "Increases in collateral axonal growth rostral to a thoracic hemisection in neonatal and weanling rat. The spinal cords of newborn and weanling rats were hemisected at the mid-thoracic level. Control studies revealed that Fink-Heimer positive debris was absent in the gray matter at three months postoperative. The remaining animals were given a second lesion, a high cervical spinal hemisection, at five to seven months after the original thoracic hemisection. The pattern of degeneration rostal to the thoracic lesion was compared with similar regions of the spinal cord from animals receiving only a cervical hemisection at the adult stage. In neither experimental group of doubly hemisected rats was there any degeneration observed below the thoracic lesion site, even though no glial or connective tissue scar had formed in animals originally operated at birth. Thus no regeneration had occurred. At least one segment above the initial hemisection: 1. the majority of degenerating axons were localized toward the lateral edge of the spinal cord, especially in the doubly lesioned neonatal group; 2. the erae of ipsilateral white matter was reduced more in the neonatal than the weanling operates; 3. there was an upward shift in axonal diameter of ipsilateral fibers in both the region of the rubrospinal tract and the ventrolateral portion of the lateral funiculus of the doubly hemisected rats when compared with the cervically lesioned controls; 4. a significantly greater amount of degeneration was present in lamina VII of Rexed in both the neonatal and weanling experimental operates (p less than 0.05 weanling; p less than 0.001 neonate); 5. no mean difference in area was seen between the ipsilateral and contralateral gray matter in any group for the segments of the spinal cord in which the judgements and measurements were taken. These data suggest that there has been sprouting of axons from descending nerve tracts rostral to the thoracic lesion in both the neonatal and weanling experimental groups. The question remains whether the sprouting of descending nerve tracts is from collateral of axons which normally project rostral to the thoracic hemisection and are not cut by the thoracic lesion (collateral sprouting) or from collaterals of lesioned axons (regenerative sprouting). Present evidence favors collateral sprouting, expecially in the neonatal operate where much retrograde cell death appears to have taken place."} {"id": "PMID:1262553", "title": "Changes in the magnocellular portion of the red nucleus following thoracic hemisection in the neonatal and adult rat.", "content": "The spinal cords of newborn (0-3 day old) and adult rats were mid-thoracically hemisected. Ninety days later a glial and connective tissue scar had formed at the lesion site in the adult hemisected rats while in neonatally lesioned animals only normal appearing regions of the contralateral spinal cord were found in the area of hemisection. Comparisons of the magnocellular portions of the red nucleus (MPRN) revealed a decrease in cell number in the MPRN contralateral (C-MPRN) to the spinal lesion. However, only in the newborn operates was there massive cell loss accompanied by reduction in area and change in shape of the nucleus. These changes were most obvious in the caudal and ventrolateral portions of the C-MPRN. Pooled data from each group of operates indicated that significantly more cells were lost in the C-MPRN in the newborn than in the adult operates (p less than 0.01). Neurons of the C-MPRN which are known to project to the lower cervical and upper thoracic segments of the spinal cord (Brown, '74; Gwyn, '71) remained undamaged after the mid-thoracic hemisection in both groups. However, neurons of this region were enlarged in both groups when compared to a similar region of the ipsilateral MPRN. These neurons were found to be more enlarged in the newborn than in the adult operates (p less than 0.01). This result indicates that massive retrograde cell death takes place after a mid-thoracic hemisection in the neonatal rat. The retrograde degeneration of axotomized neurons partially may explain why CNS regeneration is not found in the immature mammal even though many of the factors thought to limit regeneration in the adult mammal may not be apparent. The increase in cell size of C-MPRN neurons which remain in the neonatal animals after mid-thoracic hemisection may be related to the increase in axonal size found in the region of the rubrospinal tract rostral to the thoracic lesion reported earlier (Prendergast and Stelzner, '76a). Both the increase in axonal and perikaryal size are hypothesized to be related to the increased distribution of supraspinal axons found in the gray matter rostral to a hemisection of the neonatal rat spinal cord.", "contents": "Changes in the magnocellular portion of the red nucleus following thoracic hemisection in the neonatal and adult rat. The spinal cords of newborn (0-3 day old) and adult rats were mid-thoracically hemisected. Ninety days later a glial and connective tissue scar had formed at the lesion site in the adult hemisected rats while in neonatally lesioned animals only normal appearing regions of the contralateral spinal cord were found in the area of hemisection. Comparisons of the magnocellular portions of the red nucleus (MPRN) revealed a decrease in cell number in the MPRN contralateral (C-MPRN) to the spinal lesion. However, only in the newborn operates was there massive cell loss accompanied by reduction in area and change in shape of the nucleus. These changes were most obvious in the caudal and ventrolateral portions of the C-MPRN. Pooled data from each group of operates indicated that significantly more cells were lost in the C-MPRN in the newborn than in the adult operates (p less than 0.01). Neurons of the C-MPRN which are known to project to the lower cervical and upper thoracic segments of the spinal cord (Brown, '74; Gwyn, '71) remained undamaged after the mid-thoracic hemisection in both groups. However, neurons of this region were enlarged in both groups when compared to a similar region of the ipsilateral MPRN. These neurons were found to be more enlarged in the newborn than in the adult operates (p less than 0.01). This result indicates that massive retrograde cell death takes place after a mid-thoracic hemisection in the neonatal rat. The retrograde degeneration of axotomized neurons partially may explain why CNS regeneration is not found in the immature mammal even though many of the factors thought to limit regeneration in the adult mammal may not be apparent. The increase in cell size of C-MPRN neurons which remain in the neonatal animals after mid-thoracic hemisection may be related to the increase in axonal size found in the region of the rubrospinal tract rostral to the thoracic lesion reported earlier (Prendergast and Stelzner, '76a). Both the increase in axonal and perikaryal size are hypothesized to be related to the increased distribution of supraspinal axons found in the gray matter rostral to a hemisection of the neonatal rat spinal cord."} {"id": "PMID:1262554", "title": "A somatotopic and functional representation of the respiratory muscles in the trigeminal and facial motor nuclei of the carp (Cyprinus carpio L.).", "content": "The place of the cells innervating six most important respiratory muscles in the carp (Cyprinus carpio L.) were determined by means of the horseradish peroxidase technique. It was found that these muscles are represented in the rostral and caudal subdivisions of the trigeminal and facial motor nuclei. All connections were ipsilateral. The distribution of the various cell populations over the different subnuclei has been related to the function of the respective muscles in the respiratory cycle. On these grounds it could be concluded that muscles active in the contraction phase of respiration are represented in the rostral subnuclei, the expansion muscles in the caudal subnuclei. This arrangement appears to be a compromise between a somatotopic and functional and functional organization.", "contents": "A somatotopic and functional representation of the respiratory muscles in the trigeminal and facial motor nuclei of the carp (Cyprinus carpio L.). The place of the cells innervating six most important respiratory muscles in the carp (Cyprinus carpio L.) were determined by means of the horseradish peroxidase technique. It was found that these muscles are represented in the rostral and caudal subdivisions of the trigeminal and facial motor nuclei. All connections were ipsilateral. The distribution of the various cell populations over the different subnuclei has been related to the function of the respective muscles in the respiratory cycle. On these grounds it could be concluded that muscles active in the contraction phase of respiration are represented in the rostral subnuclei, the expansion muscles in the caudal subnuclei. This arrangement appears to be a compromise between a somatotopic and functional and functional organization."} {"id": "PMID:1262555", "title": "Postnatal maturation of rat Purkinje cells cultivated in the absence of two afferent systems: an ultrastructural study.", "content": "Organized cultures of newborn rat cerebellum were established in Maximow chambers in order to study the maturation of Purkinje cells in absence of afferent systems. In the first model, standard cultures were devoid of extracerebellar afferents mossy and climbing fibers. Despite this absence, somatic spines appeared upon Purkinje cells during the first week in vitro and maturation proceeded normally except for the almost absence of spiny branchlets. Large dendritic trunks were studded with numerous spines, some of which were naked, a few bearing isolated post-synaptic densities and others occupied by boutons of parallel fibers. Stellate and basket axons made synapses upon the smooth portions of dendrites and soma. In a second model, the cultures were fed the antimitotic drug methylazoxymethanol (MAM) to prevent multiplication of granule cell precursors. Despite the absence of climbing and parallel fibers, the elongation of Purkinje dendrites was not prevented, but again the dendritic arbor consisted of large trunks studded with spines; somatic as well as dendritic spines were contacted by large boutons identified as Purkinje recurrent collaterals (PRC). It is concluded that the Purkinje cell possesses a large autonomy from afferent systems as to the growth of soma and dendrites. Conversely, the geometry of the dendrite and especially the spiny branchlets depend on the presence of both climbing and parallel fibers. One may conclude from the above experiments that specificity of synaptic contacts is maintained as long as postsynaptic sites are not devoid of their normal afferents. Heterologous synapses are formed when postsynaptic sites are present, their normal afferents absent and aberrant ones increasing by collateral sprouting. Such is probably the case in the second model of this study.", "contents": "Postnatal maturation of rat Purkinje cells cultivated in the absence of two afferent systems: an ultrastructural study. Organized cultures of newborn rat cerebellum were established in Maximow chambers in order to study the maturation of Purkinje cells in absence of afferent systems. In the first model, standard cultures were devoid of extracerebellar afferents mossy and climbing fibers. Despite this absence, somatic spines appeared upon Purkinje cells during the first week in vitro and maturation proceeded normally except for the almost absence of spiny branchlets. Large dendritic trunks were studded with numerous spines, some of which were naked, a few bearing isolated post-synaptic densities and others occupied by boutons of parallel fibers. Stellate and basket axons made synapses upon the smooth portions of dendrites and soma. In a second model, the cultures were fed the antimitotic drug methylazoxymethanol (MAM) to prevent multiplication of granule cell precursors. Despite the absence of climbing and parallel fibers, the elongation of Purkinje dendrites was not prevented, but again the dendritic arbor consisted of large trunks studded with spines; somatic as well as dendritic spines were contacted by large boutons identified as Purkinje recurrent collaterals (PRC). It is concluded that the Purkinje cell possesses a large autonomy from afferent systems as to the growth of soma and dendrites. Conversely, the geometry of the dendrite and especially the spiny branchlets depend on the presence of both climbing and parallel fibers. One may conclude from the above experiments that specificity of synaptic contacts is maintained as long as postsynaptic sites are not devoid of their normal afferents. Heterologous synapses are formed when postsynaptic sites are present, their normal afferents absent and aberrant ones increasing by collateral sprouting. Such is probably the case in the second model of this study."} {"id": "PMID:1262556", "title": "Neurogenesis in the visual system of the rat. An autoradiographic investigation.", "content": "Rats of the BD III strain were injected with a single dose of 3H-thymidine on either the twelfth, fourteenth, sixteenth, eighteenth or twentieth day of gestation (ED 12. . . . .ED 20) or on the postnatal day one, three, or seven. Animals were killed at age 22 to 24 days. DNA synthesis, as an indicator of cell division, was studied in matrix precursors of nerve and glial cells in the visula centers, including the lateral geniculate body (LGB), the superior colliculus (SC) and the visual cortex (VC). It was found that proliferation of matrix precursors of nerve cells destined for all the regions studied was in progress on ED 12. In the subcortical regions (LGB, SC) this process was substantially more advanced than in the VC. The first neuroblasts appeared in the SC (ED 12) and only later (ED 14) in the LGB and VC. In comparison with the LGB, VC neuroblasts were quite rare on ED 14 and were present only in layer VI. They appeared more frequently in this region only after injection of isotope on ED 16. Matrix cell proliferation and nerve cell formation ceased in the LGB between ED 16 and ED 18. The number of labeled cells arising after injection of the isotope on ED 16 indicates that neurogenesis ceased somewhat earlier in the dorsal nucleus of the LGB than in the ventral. In the SC the last neurons arose between ED 18 and ED 20, and in the VC, with the possible exception of a few granular neurons (which may continue division into the first few days postnatally), proliferation continued until the end of gestation. The origin of neuroblasts initially followed a caudo-rostral gradient. Later, the times of neurogenesis in the regions studied overlapped significantly. This is clear, for example. on ED 16, when neurogenesis in the mesencephalic SC continued for about two days longer than in the more postral LGB, and coincided with that in the VC, especially in the deep layers. The end of neurogenesis in the LGB, especially in the ventral nucleus, coincided with the time of neurogenesis in the deep cortical layers. In the VC, and partly also in the SC, an inside-out pattern of proliferation and neuron formation was confirmed. The times of proliferation of precursor cells, with the exception of the very end of neurogenesis, substantially overlapped within both these regions. The degree of this overlapping, described in terms of Labeling Index values, decreased towards the end of the neurogenetic period. Division of neuroglial cell precursors, started as early as on ED 14 in/for subcortical centers (LGB, SC), but not until ED 18 in/for the VC. A few labeled endothelial-like cells were observed in all regions studied after isotope injection on ED 12.", "contents": "Neurogenesis in the visual system of the rat. An autoradiographic investigation. Rats of the BD III strain were injected with a single dose of 3H-thymidine on either the twelfth, fourteenth, sixteenth, eighteenth or twentieth day of gestation (ED 12. . . . .ED 20) or on the postnatal day one, three, or seven. Animals were killed at age 22 to 24 days. DNA synthesis, as an indicator of cell division, was studied in matrix precursors of nerve and glial cells in the visula centers, including the lateral geniculate body (LGB), the superior colliculus (SC) and the visual cortex (VC). It was found that proliferation of matrix precursors of nerve cells destined for all the regions studied was in progress on ED 12. In the subcortical regions (LGB, SC) this process was substantially more advanced than in the VC. The first neuroblasts appeared in the SC (ED 12) and only later (ED 14) in the LGB and VC. In comparison with the LGB, VC neuroblasts were quite rare on ED 14 and were present only in layer VI. They appeared more frequently in this region only after injection of isotope on ED 16. Matrix cell proliferation and nerve cell formation ceased in the LGB between ED 16 and ED 18. The number of labeled cells arising after injection of the isotope on ED 16 indicates that neurogenesis ceased somewhat earlier in the dorsal nucleus of the LGB than in the ventral. In the SC the last neurons arose between ED 18 and ED 20, and in the VC, with the possible exception of a few granular neurons (which may continue division into the first few days postnatally), proliferation continued until the end of gestation. The origin of neuroblasts initially followed a caudo-rostral gradient. Later, the times of neurogenesis in the regions studied overlapped significantly. This is clear, for example. on ED 16, when neurogenesis in the mesencephalic SC continued for about two days longer than in the more postral LGB, and coincided with that in the VC, especially in the deep layers. The end of neurogenesis in the LGB, especially in the ventral nucleus, coincided with the time of neurogenesis in the deep cortical layers. In the VC, and partly also in the SC, an inside-out pattern of proliferation and neuron formation was confirmed. The times of proliferation of precursor cells, with the exception of the very end of neurogenesis, substantially overlapped within both these regions. The degree of this overlapping, described in terms of Labeling Index values, decreased towards the end of the neurogenetic period. Division of neuroglial cell precursors, started as early as on ED 14 in/for subcortical centers (LGB, SC), but not until ED 18 in/for the VC. A few labeled endothelial-like cells were observed in all regions studied after isotope injection on ED 12."} {"id": "PMID:1262557", "title": "Afferents to the cerebellar lateral nucleus. Evidence from retrograde transport of horseradish peroxidase after pressure injections through micropipettes.", "content": "HRP was injected by pressure from glass capillary micropipettes unilaterally into the lateral nucleus of rat so as to encompass the entire nucleus, but without spread into the interpositus nuclei. The cells of origin of the afferents to the lateral nucleus were studied after retrograde transport of the HRP. The reticulotegmental nucleus of the pons was labelled bilaterally and is the major source of crossed and uncrossed reticular imputs. The pontine nuclei also provide extensive crossed and uncrossed afferents. The inferior olive gives a large crossed olivo-lateral nucleus projection and a minor uncrossed input. The trigeminal nuclear complex--the nucleus of the spinal tract and the mesencephalic, principal sensory, and motor nuclei--all provide uncrossed afferents. The rostral portion of the lateral reticular nucleus gives a small crossed and uncrossed projection while the perihypoglossal nuclei and the dorsal parabrachial body give crossed afferents to the lateral nucleus. The norepinephrine afferent system from the locus coeruleus is represented by one or two heavily labelled cells and the serotonin raphe systems come from at least five raphe subgroups, the dorsal, superior centralis, pontis, obscurus and magnus nuclei. No evidence was found for commissural fibers between ipsilateral or contralateral cerebellar nuclei, or afferent axons from the spinocerebellar nuclei and the paramedian retricular nucleus. The significance of these sources of afferent imputs to the lateral cerebellar nucleus is discussed. The question is raised of the direct relationship between size of terminal axonal arborization and the quantity of HRP granules present in a cell retrograde transport. The limitations of the HRP method for detecting subtle local differences in the distribution of afferents within the heterogeneous groups of neurons in the lateral nucleus are discussed.", "contents": "Afferents to the cerebellar lateral nucleus. Evidence from retrograde transport of horseradish peroxidase after pressure injections through micropipettes. HRP was injected by pressure from glass capillary micropipettes unilaterally into the lateral nucleus of rat so as to encompass the entire nucleus, but without spread into the interpositus nuclei. The cells of origin of the afferents to the lateral nucleus were studied after retrograde transport of the HRP. The reticulotegmental nucleus of the pons was labelled bilaterally and is the major source of crossed and uncrossed reticular imputs. The pontine nuclei also provide extensive crossed and uncrossed afferents. The inferior olive gives a large crossed olivo-lateral nucleus projection and a minor uncrossed input. The trigeminal nuclear complex--the nucleus of the spinal tract and the mesencephalic, principal sensory, and motor nuclei--all provide uncrossed afferents. The rostral portion of the lateral reticular nucleus gives a small crossed and uncrossed projection while the perihypoglossal nuclei and the dorsal parabrachial body give crossed afferents to the lateral nucleus. The norepinephrine afferent system from the locus coeruleus is represented by one or two heavily labelled cells and the serotonin raphe systems come from at least five raphe subgroups, the dorsal, superior centralis, pontis, obscurus and magnus nuclei. No evidence was found for commissural fibers between ipsilateral or contralateral cerebellar nuclei, or afferent axons from the spinocerebellar nuclei and the paramedian retricular nucleus. The significance of these sources of afferent imputs to the lateral cerebellar nucleus is discussed. The question is raised of the direct relationship between size of terminal axonal arborization and the quantity of HRP granules present in a cell retrograde transport. The limitations of the HRP method for detecting subtle local differences in the distribution of afferents within the heterogeneous groups of neurons in the lateral nucleus are discussed."} {"id": "PMID:1262558", "title": "On the striate area of the human isocortex. A Golgi- and pigmentarchitectonic study.", "content": "The distribution pattern of the pigment in various layers of the primary visual cortex of man is described by means of a method for the stereomicroscopical demonstration of neurolipofuscins in sections up to 1,000 mum thick. This paper presents the striate area as being composed of 12 cellular layers, which can be clearly delineated by a successive examination of both the Nissland the pigment preparations. Layers I, II, and III resemble more or less the corresponding laminae of other isocortical fields. The pyramids within the deep portion of layer III are unusually small and additionally are intermingled with thorny stellate cells which are a characteristic component of layer IV. Accordingly, this band of cells is called IIIc-IVa. The subjacent layers IVb and IVcalpha are poorly pigmented. In Nissl-preparations layer IVb, which contains only a few cells, is followed by a broad band of cells tightly packed together, which includes layers IVcalpha, IVcbeta, IVd, and Va. These layers cannot be reliably delineated in Nissl-preparations but appear in pigment preparations as distinct and sharply limited laminae. Particularly, layer IVcbeta, which is built up by minute thorny stellate cells, is marked by coarse and intensely stained lipofuscin granules, whereas IVd is mainly populated by minute pyramids which are almost devoid of pigment deposits. A remarkably narrowed layer Va, the pyramids of which store a medium number of lipofuscin grains, completes this series (IVcalpha, IVcbeta, IVd, Va). The cell-sparse layer Vb is almost devoid of pigment granules. Layer VIa has specialized pyramidal cells containing finely grained pigment. The relatively broad layer VIb shows loosely arranged cells poorly endowed with lipofuscin granules.", "contents": "On the striate area of the human isocortex. A Golgi- and pigmentarchitectonic study. The distribution pattern of the pigment in various layers of the primary visual cortex of man is described by means of a method for the stereomicroscopical demonstration of neurolipofuscins in sections up to 1,000 mum thick. This paper presents the striate area as being composed of 12 cellular layers, which can be clearly delineated by a successive examination of both the Nissland the pigment preparations. Layers I, II, and III resemble more or less the corresponding laminae of other isocortical fields. The pyramids within the deep portion of layer III are unusually small and additionally are intermingled with thorny stellate cells which are a characteristic component of layer IV. Accordingly, this band of cells is called IIIc-IVa. The subjacent layers IVb and IVcalpha are poorly pigmented. In Nissl-preparations layer IVb, which contains only a few cells, is followed by a broad band of cells tightly packed together, which includes layers IVcalpha, IVcbeta, IVd, and Va. These layers cannot be reliably delineated in Nissl-preparations but appear in pigment preparations as distinct and sharply limited laminae. Particularly, layer IVcbeta, which is built up by minute thorny stellate cells, is marked by coarse and intensely stained lipofuscin granules, whereas IVd is mainly populated by minute pyramids which are almost devoid of pigment deposits. A remarkably narrowed layer Va, the pyramids of which store a medium number of lipofuscin grains, completes this series (IVcalpha, IVcbeta, IVd, Va). The cell-sparse layer Vb is almost devoid of pigment granules. Layer VIa has specialized pyramidal cells containing finely grained pigment. The relatively broad layer VIb shows loosely arranged cells poorly endowed with lipofuscin granules."} {"id": "PMID:1262559", "title": "Cell growth in the lateral geniculate nucleus of kittens following the opening or closing of one eye.", "content": "Closing one eye of kittens at 23 days after birth resulted in paler Nissl staining of the deprived cells in the lateral geniculate nucleus (LGN) that was detectable two days later. Differences between the two sides of the brain in mean cell area increased to a peak in binocular lamina A at 4--6 days after eyelid suture, and then fell to a trough at eight days before rising progressively to a higher level at 31 days. In lamina A1 the peak and trough were later. Opening one eye of kittens after 23 days of binocular closure from birth resulted in more intense Nissl staining of the stimulated cells in the LGN that was detectable four days later. The stimulated cells grew faster than the cells connected to the eye that remained closed, and this differential growth reached a peak at 17 days in binocular lamina A and at 21 days in lamina A1 before falling to a trough at 26--31 days. These results are compared with the time course of anabolic changes that have been measured in other neurons during stimulation. The coefficient of variation of cell size was computed and found to be slightly decreased for deprived cells and increased for stimulated cells. This suggests that larger cells changes their sizes proportionately more than smaller cells. The cells were measured in fronzen sections without shrinkage, and the areas are at least 25% larger than those reported previously after paraffin or celloidin embedding.", "contents": "Cell growth in the lateral geniculate nucleus of kittens following the opening or closing of one eye. Closing one eye of kittens at 23 days after birth resulted in paler Nissl staining of the deprived cells in the lateral geniculate nucleus (LGN) that was detectable two days later. Differences between the two sides of the brain in mean cell area increased to a peak in binocular lamina A at 4--6 days after eyelid suture, and then fell to a trough at eight days before rising progressively to a higher level at 31 days. In lamina A1 the peak and trough were later. Opening one eye of kittens after 23 days of binocular closure from birth resulted in more intense Nissl staining of the stimulated cells in the LGN that was detectable four days later. The stimulated cells grew faster than the cells connected to the eye that remained closed, and this differential growth reached a peak at 17 days in binocular lamina A and at 21 days in lamina A1 before falling to a trough at 26--31 days. These results are compared with the time course of anabolic changes that have been measured in other neurons during stimulation. The coefficient of variation of cell size was computed and found to be slightly decreased for deprived cells and increased for stimulated cells. This suggests that larger cells changes their sizes proportionately more than smaller cells. The cells were measured in fronzen sections without shrinkage, and the areas are at least 25% larger than those reported previously after paraffin or celloidin embedding."} {"id": "PMID:1262560", "title": "Efferent connections of the caudate nucleus in the Virginia opossum.", "content": "The efferents of the opossum's caudate nucleus were investigated by charting the the fiber degenerations produced by electrolytic lesions in various parts of this nucleus. By the aid of a modified Fink-Heimer procedure, degenerating fibers were traced from each of the lesions to the small globus pallidus in which they appeared to be distributed in an orderly dorsoventral pattern. Fibers from all lesion sites in the caudate nucleus were found to terminate in the entopedunucular nucleus. In the substantia nigra, caudatofugal-fiber degeneration was confined in all cases to the rostal part of the pars reticulata, and was densest in the medial one-half of this nucleus. Only from lesions in the ventromedial part of the caudate nucleus could degenerating fibers be traced to the nucleus ansae lenticularis. No fiber degeneration could be traced rostrally from the lesions, or to the putamen, red nucleus, subthalamic nucleus, or pons.", "contents": "Efferent connections of the caudate nucleus in the Virginia opossum. The efferents of the opossum's caudate nucleus were investigated by charting the the fiber degenerations produced by electrolytic lesions in various parts of this nucleus. By the aid of a modified Fink-Heimer procedure, degenerating fibers were traced from each of the lesions to the small globus pallidus in which they appeared to be distributed in an orderly dorsoventral pattern. Fibers from all lesion sites in the caudate nucleus were found to terminate in the entopedunucular nucleus. In the substantia nigra, caudatofugal-fiber degeneration was confined in all cases to the rostal part of the pars reticulata, and was densest in the medial one-half of this nucleus. Only from lesions in the ventromedial part of the caudate nucleus could degenerating fibers be traced to the nucleus ansae lenticularis. No fiber degeneration could be traced rostrally from the lesions, or to the putamen, red nucleus, subthalamic nucleus, or pons."} {"id": "PMID:1262561", "title": "The effect of frequency of feeding on milk secretion in the Ayrshire cow.", "content": "Four Ayrshire cows in their second lactation were used in a 4 X 4 Latin square experiment to determine the effects of frequency of feeding on milk secretion. The animals were given a diet consisting of hay, sugar-beet pulp and dairy concentrates (34-9:19-7:45-5 on a dry-matter basis) either in 2 equal meals/d at 07.00 and 17.00 h or with the hay in 4 meals at 07.00, 12.00, 17.00 and 22.00 h and the sugar-beet pulp and concentrates in 24-h meals. Each feeding frequency was tested at 2 levels of feeding providing either 100 or 80% of the standard requirements for energy. There were no significant effects of frequency of feeding on milk yield or on the milk content of fat, protein, lactose, solids-not-fat or total solids, but underfeeding depressed the yield of milk and of all milk constituents. Neither the frequency nor level of feeding had appreciable effects on the fatty-acid composition of the milk fat or on the blood glucose concentration, but in animals fed frequently plasma urea levels were lower than in animals fed twice daily and there was no postprandial peak in urea concentration.", "contents": "The effect of frequency of feeding on milk secretion in the Ayrshire cow. Four Ayrshire cows in their second lactation were used in a 4 X 4 Latin square experiment to determine the effects of frequency of feeding on milk secretion. The animals were given a diet consisting of hay, sugar-beet pulp and dairy concentrates (34-9:19-7:45-5 on a dry-matter basis) either in 2 equal meals/d at 07.00 and 17.00 h or with the hay in 4 meals at 07.00, 12.00, 17.00 and 22.00 h and the sugar-beet pulp and concentrates in 24-h meals. Each feeding frequency was tested at 2 levels of feeding providing either 100 or 80% of the standard requirements for energy. There were no significant effects of frequency of feeding on milk yield or on the milk content of fat, protein, lactose, solids-not-fat or total solids, but underfeeding depressed the yield of milk and of all milk constituents. Neither the frequency nor level of feeding had appreciable effects on the fatty-acid composition of the milk fat or on the blood glucose concentration, but in animals fed frequently plasma urea levels were lower than in animals fed twice daily and there was no postprandial peak in urea concentration."} {"id": "PMID:1262564", "title": "Formation of acetaldehyde from threonine by lactic acid bacteria.", "content": "Group N streptococci were found to cleave threonine to form acetaldehyde and glycine. Threonine aldolase, the enzyme catalysing this reaction, was found in all strains except Streptococcus cremoris Z8, an organism which had been shown previously to have a nutritional requirement for glycine. The enzyme was strongly inhibited by glycine and cysteine. The inhibition showed characteristics of allosteric inhibition and was pH-dependent. Inhibition by glycine, but not by cysteine, was highly specific. Analogues and derivatives of cysteine which contained a thiol group and a free amino group inhibited the activity of threonine aldolase. The presence of a carboxyl group was not necessary for inhibition. The cleavage of threonine by whole-cell suspensions was stimulated by either an energy source to aid transport or by rendering the cells permeable to substrate with oleate. Threonine did not appear to be degraded by enzymes other than threonine aldolase, as threonine dehydratase activity was low and NAD- and NADP-dependent threonine dehydrogenases were absent.", "contents": "Formation of acetaldehyde from threonine by lactic acid bacteria. Group N streptococci were found to cleave threonine to form acetaldehyde and glycine. Threonine aldolase, the enzyme catalysing this reaction, was found in all strains except Streptococcus cremoris Z8, an organism which had been shown previously to have a nutritional requirement for glycine. The enzyme was strongly inhibited by glycine and cysteine. The inhibition showed characteristics of allosteric inhibition and was pH-dependent. Inhibition by glycine, but not by cysteine, was highly specific. Analogues and derivatives of cysteine which contained a thiol group and a free amino group inhibited the activity of threonine aldolase. The presence of a carboxyl group was not necessary for inhibition. The cleavage of threonine by whole-cell suspensions was stimulated by either an energy source to aid transport or by rendering the cells permeable to substrate with oleate. Threonine did not appear to be degraded by enzymes other than threonine aldolase, as threonine dehydratase activity was low and NAD- and NADP-dependent threonine dehydrogenases were absent."} {"id": "PMID:1262565", "title": "A rumen linear programming model for evaluation of concepts of rumen microbial function.", "content": "A linear programming model provides for analysis of general input-output relationships in the rumen, for evaluation of competitive relationships among rumen microbes, and for computation of optimal relationships in the rumen. Eight rumen microbial groups defined on the bases of substrate specificity, nutrient requirements for growth, fermentation products, and relative metabolic activities comprise the central core of the model. Relative metabolic rates of microbial groups calculated from their cell sized were used as coefficients in the objective function. The model was used to evaluate effects of different amounts of protein from feed and various carbohydrates upon microbial population and fermentation patterns as accommodated by current concepts. During the several solutions of the model, considerable simplification of the rumen microflora occurred. This implies that current data and concepts, and the hypothesis regarding relative metabolic rate, as represented in the model, do not accommodate adequately competitions among the several rumen microbial species and, thus, that additional data and concepts regarding rumen microbial interactions are required. Also evaluated were effects of ingestion of bacteria by protozoa upon over-all rumen function, absolute microbial cell yields, cell yields per mole of adenosine triphosphate, and factors affecting these.", "contents": "A rumen linear programming model for evaluation of concepts of rumen microbial function. A linear programming model provides for analysis of general input-output relationships in the rumen, for evaluation of competitive relationships among rumen microbes, and for computation of optimal relationships in the rumen. Eight rumen microbial groups defined on the bases of substrate specificity, nutrient requirements for growth, fermentation products, and relative metabolic activities comprise the central core of the model. Relative metabolic rates of microbial groups calculated from their cell sized were used as coefficients in the objective function. The model was used to evaluate effects of different amounts of protein from feed and various carbohydrates upon microbial population and fermentation patterns as accommodated by current concepts. During the several solutions of the model, considerable simplification of the rumen microflora occurred. This implies that current data and concepts, and the hypothesis regarding relative metabolic rate, as represented in the model, do not accommodate adequately competitions among the several rumen microbial species and, thus, that additional data and concepts regarding rumen microbial interactions are required. Also evaluated were effects of ingestion of bacteria by protozoa upon over-all rumen function, absolute microbial cell yields, cell yields per mole of adenosine triphosphate, and factors affecting these."} {"id": "PMID:1262566", "title": "Growth and morphology of Streptococcus bovis and of mixed rumen bacteria in the presence of aflatoxin B1, in vitro.", "content": "The metabolism of aflatoxin B1 to other fluorescent compounds was studied in rumen organisms. No fluorescent metabolites were found by chromatographic procedures which separate aflatoxin B1 from them. Rumen bacteria (mixtures and Streptococcus bovis) incubated with aflatoxin B1 grew in long chains whereas cells in control cultures were mainly doublets with some short chains. Growth of mixed rumen bacteria and Streptococcus bovis cultures was inhibited by aflatoxin B1 as measured by change in optical density and by incorporation of [carbon-14] adenine into nucleic acids.", "contents": "Growth and morphology of Streptococcus bovis and of mixed rumen bacteria in the presence of aflatoxin B1, in vitro. The metabolism of aflatoxin B1 to other fluorescent compounds was studied in rumen organisms. No fluorescent metabolites were found by chromatographic procedures which separate aflatoxin B1 from them. Rumen bacteria (mixtures and Streptococcus bovis) incubated with aflatoxin B1 grew in long chains whereas cells in control cultures were mainly doublets with some short chains. Growth of mixed rumen bacteria and Streptococcus bovis cultures was inhibited by aflatoxin B1 as measured by change in optical density and by incorporation of [carbon-14] adenine into nucleic acids."} {"id": "PMID:1262567", "title": "Effect of sampling location, time, and method of concentration of ammonia nitrogen in rumen fluid.", "content": "In experiment 1, rumen fluid samples were obtained from dorsal, midpoint, and ventral regions of the rumen of rumenfistulated dairy cows at hourly intervals for 24 h. Dorsal, midpoint, and ventral rumen fluid samples contained 16.1, 14.2, and 12.1 mg/100 ml of ammonia nitrogen. Time after feeding resulted in differences in the concentration of ammonia in rumen fluid with the greatest concentration 30 to 90 min postfeeding. The concentration of ammonia nitrogen was greater for cows fed a high-concentrate diet (14.7% crude protein, 86% concentrate) than for cows receiving a normal diet (15.1% crude protein, 42% concentrate), 15.2 versus 13.1 mg/100 ml. In a second experiment, rumen fluid samples were obtained immediately before feeding and at 1 and 6 h postfeeding by stomach tube and from dorsal, midpoint, ventral, and mixed rumen contents via a rumen cannula. Concentrations of ammonia nitrogen (mg/100 ml) in the respective rumen fluid samples were 14.3, 23.0, 18.3, 17.2, and 19.6. Location of sampling, method of sampling, time of sampling, type of diet, and rumen fluid volume are factors that affect the concentration of ammonia nitrogen in rumen fluid.", "contents": "Effect of sampling location, time, and method of concentration of ammonia nitrogen in rumen fluid. In experiment 1, rumen fluid samples were obtained from dorsal, midpoint, and ventral regions of the rumen of rumenfistulated dairy cows at hourly intervals for 24 h. Dorsal, midpoint, and ventral rumen fluid samples contained 16.1, 14.2, and 12.1 mg/100 ml of ammonia nitrogen. Time after feeding resulted in differences in the concentration of ammonia in rumen fluid with the greatest concentration 30 to 90 min postfeeding. The concentration of ammonia nitrogen was greater for cows fed a high-concentrate diet (14.7% crude protein, 86% concentrate) than for cows receiving a normal diet (15.1% crude protein, 42% concentrate), 15.2 versus 13.1 mg/100 ml. In a second experiment, rumen fluid samples were obtained immediately before feeding and at 1 and 6 h postfeeding by stomach tube and from dorsal, midpoint, ventral, and mixed rumen contents via a rumen cannula. Concentrations of ammonia nitrogen (mg/100 ml) in the respective rumen fluid samples were 14.3, 23.0, 18.3, 17.2, and 19.6. Location of sampling, method of sampling, time of sampling, type of diet, and rumen fluid volume are factors that affect the concentration of ammonia nitrogen in rumen fluid."} {"id": "PMID:1262568", "title": "Hexachlorobenzene retention and excretion by dairy cows.", "content": "Two groups of three cows each were fed either 5 or 25 mg of hexachlorobenzene per day for 60 days. A reference compound, DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), was fed to the cows at the same rate. Residues were determined in milk at 5-day intervals during the 60-day dosing period and for 60 days after dosing was stopped. The concentration of hexachlorobenzene in milk fat increased more slowly than did that of the reference compound during feeding. The ratio of the two was 1:2 at 10 days, but approached 1:1 after 40 days of feeding. The average concentrations in milk fat for the 40th to 60th days of feeding were 9.0 and 10.4 ppm with the 25-mg/day intake and 2.1 ppm for each compound with the 5-mg/day intake. Corresponding values in subcutaneous body fat were 8.8, 8.0, 1.9, and 1.4 ppm at 60 days. Milk fat concentrations of hexachlorobenzene declined 32% and those of the reference 51% within 15 days after feeding stopped. Thereafter, the decline was slower but similar for both compounds. Biological half-lives ranged from 29 to 64 days for individual cows. The milk fat:body fat concentration ratio was .87:1 for hexachlorobenzene and .71:1 for the reference during the 60 days when cows were not fed the compounds.", "contents": "Hexachlorobenzene retention and excretion by dairy cows. Two groups of three cows each were fed either 5 or 25 mg of hexachlorobenzene per day for 60 days. A reference compound, DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene), was fed to the cows at the same rate. Residues were determined in milk at 5-day intervals during the 60-day dosing period and for 60 days after dosing was stopped. The concentration of hexachlorobenzene in milk fat increased more slowly than did that of the reference compound during feeding. The ratio of the two was 1:2 at 10 days, but approached 1:1 after 40 days of feeding. The average concentrations in milk fat for the 40th to 60th days of feeding were 9.0 and 10.4 ppm with the 25-mg/day intake and 2.1 ppm for each compound with the 5-mg/day intake. Corresponding values in subcutaneous body fat were 8.8, 8.0, 1.9, and 1.4 ppm at 60 days. Milk fat concentrations of hexachlorobenzene declined 32% and those of the reference 51% within 15 days after feeding stopped. Thereafter, the decline was slower but similar for both compounds. Biological half-lives ranged from 29 to 64 days for individual cows. The milk fat:body fat concentration ratio was .87:1 for hexachlorobenzene and .71:1 for the reference during the 60 days when cows were not fed the compounds."} {"id": "PMID:1262569", "title": "Effects of adrenalectomy upon ruminant liver and mammary function during lactation.", "content": "Adrenalectomized, lactating ewes treated with a mineral corticoid or a mineral corticoid plus cortisol and sham operated ewes nursing one or two lambs were in a study of physiological role(s) of glucocorticoids in lactating ruminants. Measurements of ewe and lamb weight changes; feed intake; milk yield and composition; blood potassium; metabolite oxidation rates by mammary, liver, and kidney tissue slices; glucose production in liver and kidney tissue slices; and enzyme activities in mammary and liver tissue. 1) Mammary metabolism and milk biosynthesis in ruminants are not strongly dependent on glucocorticoid. 2) Liver gluconeogenesis in ruminants appears to be regulated in part by glucocorticover and kidney of ruminants may respond differently to adrenalectomy; thus, in ruminants, kidney may not be as good an indicator of liver gluconeogenic responses as it is in rodents. 4) Liver and mammary enzymes are not affected significantly by adrenalectomy or glucocorticoid therapy. 5) Glucocorticoids play a less significant role in the regulation of liver and mammary enzyme and metabolism in sheep than in rats.", "contents": "Effects of adrenalectomy upon ruminant liver and mammary function during lactation. Adrenalectomized, lactating ewes treated with a mineral corticoid or a mineral corticoid plus cortisol and sham operated ewes nursing one or two lambs were in a study of physiological role(s) of glucocorticoids in lactating ruminants. Measurements of ewe and lamb weight changes; feed intake; milk yield and composition; blood potassium; metabolite oxidation rates by mammary, liver, and kidney tissue slices; glucose production in liver and kidney tissue slices; and enzyme activities in mammary and liver tissue. 1) Mammary metabolism and milk biosynthesis in ruminants are not strongly dependent on glucocorticoid. 2) Liver gluconeogenesis in ruminants appears to be regulated in part by glucocorticover and kidney of ruminants may respond differently to adrenalectomy; thus, in ruminants, kidney may not be as good an indicator of liver gluconeogenic responses as it is in rodents. 4) Liver and mammary enzymes are not affected significantly by adrenalectomy or glucocorticoid therapy. 5) Glucocorticoids play a less significant role in the regulation of liver and mammary enzyme and metabolism in sheep than in rats."} {"id": "PMID:1262570", "title": "Hormone induced lactation in the bovine III. Dynamics of injected and endogenous hormones.", "content": "Three lactations were induced in two cows in two trials by twice daily subcutaneous injections for seven days. Each injection contained .05 mg/kg body weight of estradiol-17beta and .125 mg/kg body weight of progesterone. Included with the hormones in trial 1 was a combination of 233 muCi of [6,7-hydrogen-3] estradiol-17beta and 12 muCi of [4-carbon-14] progesterone. During trial 2,2050 muCi of [2,4,6,7 hydrogen-3] estradiol-17beta were incorporated with the hormones for one cow and 2344 muCi of [1,2,6,7 hydrogen-3] progesterone for the other. Radioactivity from hydrogen-3 and carbon-14 was detected in urine and feces but not in mammary secretion during trial 1. Isotope recovery from [hydrogen-3] estradiol-17beta was too low to quantify. By day 17, 90% of the carbon-14 from progesterone was accumulated in feces and 8.0% in urine. For trial 2, recoveries of radioactivity by day 28 from urine, feces, and mammary secretions were, respectively, 32.4, 56.2, and less than .002% from [hydrogen-3] estradiol-17beta and 6.0, 87.7, and .25% from [hydrogen-3] progesterone. Estrogen and progesterone in plasma averaged 1.83 and 2.61 ng/ml during days 2 to 7. Estrogen decreased more rapidly than progesterone post-treatment, but both had decreased by days 16 to 19 when average prolactin of plasma increased. Quantitative measures of estradiol 17-beta and progesterone absorption, whether in plasma or excreta, were correlated.", "contents": "Hormone induced lactation in the bovine III. Dynamics of injected and endogenous hormones. Three lactations were induced in two cows in two trials by twice daily subcutaneous injections for seven days. Each injection contained .05 mg/kg body weight of estradiol-17beta and .125 mg/kg body weight of progesterone. Included with the hormones in trial 1 was a combination of 233 muCi of [6,7-hydrogen-3] estradiol-17beta and 12 muCi of [4-carbon-14] progesterone. During trial 2,2050 muCi of [2,4,6,7 hydrogen-3] estradiol-17beta were incorporated with the hormones for one cow and 2344 muCi of [1,2,6,7 hydrogen-3] progesterone for the other. Radioactivity from hydrogen-3 and carbon-14 was detected in urine and feces but not in mammary secretion during trial 1. Isotope recovery from [hydrogen-3] estradiol-17beta was too low to quantify. By day 17, 90% of the carbon-14 from progesterone was accumulated in feces and 8.0% in urine. For trial 2, recoveries of radioactivity by day 28 from urine, feces, and mammary secretions were, respectively, 32.4, 56.2, and less than .002% from [hydrogen-3] estradiol-17beta and 6.0, 87.7, and .25% from [hydrogen-3] progesterone. Estrogen and progesterone in plasma averaged 1.83 and 2.61 ng/ml during days 2 to 7. Estrogen decreased more rapidly than progesterone post-treatment, but both had decreased by days 16 to 19 when average prolactin of plasma increased. Quantitative measures of estradiol 17-beta and progesterone absorption, whether in plasma or excreta, were correlated."} {"id": "PMID:1262571", "title": "Mathematical modeling of the mastitis infection process.", "content": "Mastitis infection is a biological process with a serial structure and stochastic in nature. A mathematical model for this process was developed from Markov chain theory. The unit of the process was an individual quarter; and four infection processes for first, second, third, fourth or higher lactation were described. Two Markov matrices which probabilistically determine the transitions between seven mutually exclusive states at each stage of the process were defined. After its validation, the model was used to determine the lactational consequences of the mastitis infection by calculating expected milk-yield productivity. Expected milk-yield productivity for an individual quarter was .93, .88, .85, and .84 for first, second, third, and fourth or higher lactation. The expected milk yield productivity of a quarter as a function of its state at the beginning of the process also was calculated. The quarters infected but not clinical have the lowest productivity.", "contents": "Mathematical modeling of the mastitis infection process. Mastitis infection is a biological process with a serial structure and stochastic in nature. A mathematical model for this process was developed from Markov chain theory. The unit of the process was an individual quarter; and four infection processes for first, second, third, fourth or higher lactation were described. Two Markov matrices which probabilistically determine the transitions between seven mutually exclusive states at each stage of the process were defined. After its validation, the model was used to determine the lactational consequences of the mastitis infection by calculating expected milk-yield productivity. Expected milk-yield productivity for an individual quarter was .93, .88, .85, and .84 for first, second, third, and fourth or higher lactation. The expected milk yield productivity of a quarter as a function of its state at the beginning of the process also was calculated. The quarters infected but not clinical have the lowest productivity."} {"id": "PMID:1262572", "title": "Intracellular distribution of zinc and zinc-65 in calves receiving high but nontoxic amounts of zinc.", "content": "The zinc homeostatic control breakdown in cattle fed a high but nontoxic amount of zinc was investigated. Liver copper was decreased by the 600 ppm added dietary zinc indicating altered copper metabolism. However, duodenal copper, liver and duodenal iron and manganese were not affected. Zinc-65 in blood was reduced 90% by the high dietary zinc 48 h following oral zinc-65 dosing. The 600 ppm supplemental zinc increased zinc by 500% in liver, 20 times in pancreas and kidney, and 100% in the duodenum. The increased liver and duodenal zinc was confined largely to the soluble cell fraction. This concentrating of excess tissue zinc in the soluble fraction may be an adaptive mechanism which detoxifies large quantities of zinc and prevents disruption of normal cellular activity.", "contents": "Intracellular distribution of zinc and zinc-65 in calves receiving high but nontoxic amounts of zinc. The zinc homeostatic control breakdown in cattle fed a high but nontoxic amount of zinc was investigated. Liver copper was decreased by the 600 ppm added dietary zinc indicating altered copper metabolism. However, duodenal copper, liver and duodenal iron and manganese were not affected. Zinc-65 in blood was reduced 90% by the high dietary zinc 48 h following oral zinc-65 dosing. The 600 ppm supplemental zinc increased zinc by 500% in liver, 20 times in pancreas and kidney, and 100% in the duodenum. The increased liver and duodenal zinc was confined largely to the soluble cell fraction. This concentrating of excess tissue zinc in the soluble fraction may be an adaptive mechanism which detoxifies large quantities of zinc and prevents disruption of normal cellular activity."} {"id": "PMID:1262573", "title": "Composition of the milks of dairy cattle. II. Ash, calcium, magnesium, and phosphorus.", "content": "Milks from commercial dairy herds in Southeastern Pennsylvania were analyzed for ash, calcium, magnesium, and phosphorus. Milk samples were from single milkings of 151 healthy purebred cows in midlactation. The data represent market milk composition. Average values for all animals were ash .78%, calcium 1.25 g/liter, magnesium .11 g/liter, and phosphorus 1.14 g/liter. The data also were grouped and analyzed by breed and beta-lactoglobulin phenotype. Breeds differed in all inorganic components with 18 to 33 cows per breed. No differences in ash, calcium, magnesium, or phosphorus were significant when the data were grouped by beta-lactoglobulin phenotype.", "contents": "Composition of the milks of dairy cattle. II. Ash, calcium, magnesium, and phosphorus. Milks from commercial dairy herds in Southeastern Pennsylvania were analyzed for ash, calcium, magnesium, and phosphorus. Milk samples were from single milkings of 151 healthy purebred cows in midlactation. The data represent market milk composition. Average values for all animals were ash .78%, calcium 1.25 g/liter, magnesium .11 g/liter, and phosphorus 1.14 g/liter. The data also were grouped and analyzed by breed and beta-lactoglobulin phenotype. Breeds differed in all inorganic components with 18 to 33 cows per breed. No differences in ash, calcium, magnesium, or phosphorus were significant when the data were grouped by beta-lactoglobulin phenotype."} {"id": "PMID:1262574", "title": "Mammary transfer of vitamin A alcohol and ester in lactating dairy cows.", "content": "The effect of intravenous injection of vitamin A alcohol and vitamin A ester on the vitamin A concentration of bovine milk was studied. Holstein cows received either an intravenous injection of 1 million international units (IU) of vitamin A alcohol, 1 million international units of vitamin A palmitate, or served as controls. Blood serum and milk were sampled at intervals prior to and following injection. Mean concentrations of vitamin A in milk at time 0 were 59.0, 52.0, and 58.4 mug/100 ml for the control, alcohol, and palmitate treatments. Mean contrations of vitamin A in milk, expressed as mug/100 ml or mug/g fat of cows receiving vitamin A alcohol at +195, +451, and +678 min postinjection, were greater than concentrations for either control cows or cows receiving palmitate. Partition of milk Vitamin A at +195 min postinjection for cows injected with vitamin A alcohol showed 4.1% of the recovered vitamin A in the alcohol and 95.9% in the ester form. Injection of vitamin A palmitate had little effect on milk vitamin A concentration. Vitamin A in serum (mug/100 ml) at 195 min after vitamin A alcohol injection was higher (100.4) than for either control (84.0) or cows injected with vitamin A palmitate (89.0).", "contents": "Mammary transfer of vitamin A alcohol and ester in lactating dairy cows. The effect of intravenous injection of vitamin A alcohol and vitamin A ester on the vitamin A concentration of bovine milk was studied. Holstein cows received either an intravenous injection of 1 million international units (IU) of vitamin A alcohol, 1 million international units of vitamin A palmitate, or served as controls. Blood serum and milk were sampled at intervals prior to and following injection. Mean concentrations of vitamin A in milk at time 0 were 59.0, 52.0, and 58.4 mug/100 ml for the control, alcohol, and palmitate treatments. Mean contrations of vitamin A in milk, expressed as mug/100 ml or mug/g fat of cows receiving vitamin A alcohol at +195, +451, and +678 min postinjection, were greater than concentrations for either control cows or cows receiving palmitate. Partition of milk Vitamin A at +195 min postinjection for cows injected with vitamin A alcohol showed 4.1% of the recovered vitamin A in the alcohol and 95.9% in the ester form. Injection of vitamin A palmitate had little effect on milk vitamin A concentration. Vitamin A in serum (mug/100 ml) at 195 min after vitamin A alcohol injection was higher (100.4) than for either control (84.0) or cows injected with vitamin A palmitate (89.0)."} {"id": "PMID:1262575", "title": "Lactational response of dairy cows to oral administration of a synthetic glucocorticoid.", "content": "Effects of oral administration of 0, 5, 10, or 20 mug of 6 alpha, 9 alpha-difluoro-16alpha-methyl-prednisolone (Flumethasone) daily on milk and milk component yields, udder health reproductive performance, and body weight change were measured. With 24 Holstein cows in a randomized block design, daily Flumethasone administration was initiated 4 days postpartum and continued until milk secretion ceased or the completion of 305 days on treatment. Mature equivalent yields (adjusted for days open) of milk, solids-not-fat, and milk fat were higher for cows receiving 5 or 10 mug Flumethasone than for cows receiving 0 or 20 mug Flumethasone daily. Lactations for cows receiving 20 mug Flumethasone were 37 to 48 days shorter than lactations for cows in other treatment groups. There were no differences between treatment groups for measures of udder health, reproductive efficiency, and body weight changes. A second experiment of 45 Holstein cows in their second or third lactations included treatments 0, 5, or 10 mug Flumethasone daily for 25 days followed by a 5 day withdrawal. Treatments were begun between day 210 and day 270 of lactation. During the 30 days, Flumethasone failed to alter milk production. These experiments indicate that Flumethasone given continuously increased milk components and milk yield but had no significant effect on milk yield when given only during the latter stage of lactation.", "contents": "Lactational response of dairy cows to oral administration of a synthetic glucocorticoid. Effects of oral administration of 0, 5, 10, or 20 mug of 6 alpha, 9 alpha-difluoro-16alpha-methyl-prednisolone (Flumethasone) daily on milk and milk component yields, udder health reproductive performance, and body weight change were measured. With 24 Holstein cows in a randomized block design, daily Flumethasone administration was initiated 4 days postpartum and continued until milk secretion ceased or the completion of 305 days on treatment. Mature equivalent yields (adjusted for days open) of milk, solids-not-fat, and milk fat were higher for cows receiving 5 or 10 mug Flumethasone than for cows receiving 0 or 20 mug Flumethasone daily. Lactations for cows receiving 20 mug Flumethasone were 37 to 48 days shorter than lactations for cows in other treatment groups. There were no differences between treatment groups for measures of udder health, reproductive efficiency, and body weight changes. A second experiment of 45 Holstein cows in their second or third lactations included treatments 0, 5, or 10 mug Flumethasone daily for 25 days followed by a 5 day withdrawal. Treatments were begun between day 210 and day 270 of lactation. During the 30 days, Flumethasone failed to alter milk production. These experiments indicate that Flumethasone given continuously increased milk components and milk yield but had no significant effect on milk yield when given only during the latter stage of lactation."} {"id": "PMID:1262576", "title": "Effect of adrenalectomy on rat mammary metabolism.", "content": "Rates and patterns of metabolism of specifically labeled glucose, pyruvate, and acetate by mammary slices indicated that rates of glucose metabolism through the Embden-Meyerhof and pentose phosphate pathways and relative pentose cycle activity were decreased by adrenalectomy. Fatty acid synthesis from acetate was not impaired. Capacity to provide reduced nicotinamide adenine dinucleotide phosphate for fatty acid synthesis was not the limiting factor responsible for decreased fatty acid synthesis from glucose in adrenalectomized, lactating rat mammary glands. Oxidation of [1-carbon-14]pyruvate and fatty acid synthesis from [2-carbon-14] pyruvate were not affected by adrenalectomy. Indirect reasoning based upon the data reported led to the suggestion that decreased fatty acid synthesis from glucose after adrenalectomy may have resulted from decreased formation of triose phosphate via the phosphofructose-kinase reaction. It is suggested further that most of the decreases in rat mammary enzyme after adrenalectomy have no direct (causative) relationship to depressed lactational performance after adrenalectomy. Restriction of food intake caused decreased fatty acid synthesis from glucose, pyruvate, and acetate, but relative fatty acid esterification activity was higher than in control and adrenalectomized animals. The effects of adrenalectomy on mammary gland metabolism can be dissociated partially from reduced food intake.", "contents": "Effect of adrenalectomy on rat mammary metabolism. Rates and patterns of metabolism of specifically labeled glucose, pyruvate, and acetate by mammary slices indicated that rates of glucose metabolism through the Embden-Meyerhof and pentose phosphate pathways and relative pentose cycle activity were decreased by adrenalectomy. Fatty acid synthesis from acetate was not impaired. Capacity to provide reduced nicotinamide adenine dinucleotide phosphate for fatty acid synthesis was not the limiting factor responsible for decreased fatty acid synthesis from glucose in adrenalectomized, lactating rat mammary glands. Oxidation of [1-carbon-14]pyruvate and fatty acid synthesis from [2-carbon-14] pyruvate were not affected by adrenalectomy. Indirect reasoning based upon the data reported led to the suggestion that decreased fatty acid synthesis from glucose after adrenalectomy may have resulted from decreased formation of triose phosphate via the phosphofructose-kinase reaction. It is suggested further that most of the decreases in rat mammary enzyme after adrenalectomy have no direct (causative) relationship to depressed lactational performance after adrenalectomy. Restriction of food intake caused decreased fatty acid synthesis from glucose, pyruvate, and acetate, but relative fatty acid esterification activity was higher than in control and adrenalectomized animals. The effects of adrenalectomy on mammary gland metabolism can be dissociated partially from reduced food intake."} {"id": "PMID:1262578", "title": "Factors influencing rumen microbial growth rates and yields: effects of urea and amino acids over time.", "content": "Washed cell suspensions of mixed rumen bacteria were used to evaluate effects of 100% urea-nitrogen and 75% urea-nitrogen plus 25% amino acid-nitrogen in growth media upon microbial growth rate and yield, specific rate of glucose consumption, and incorporation of glucose into mixed cells, carbon dioxide, and end products. Rumen microbial dry matter, nitrogen, ribonucleic acid, deoxyribonucleic acid, glucose disappearance, and production of volatile fatty acids were considerably higher in medium containing urea plus amino acids as compared with urea only. Specific growth rates of microbes were .104 and .203 and mean doubling times were 6.7 and 3.4 h in the urea and urea plus amino acid growth media. Microbial growth in mg per 100 mg glucose used, per mole glucose and per mole adenosine triphosphate (ATP), and specific rate of glucose consumption in mmol per mg cells-h were 19.3, 34.7, 15.4, and .016 with urea, and 24.4, 44.2, 20.6, and .014 with urea plus amino acids. Percentages of catabolized glucose incorporated into microbial cells, carbon dioxide, and end products did not differ between treatments and averaged 19.5, 7.8, and 64.4%.", "contents": "Factors influencing rumen microbial growth rates and yields: effects of urea and amino acids over time. Washed cell suspensions of mixed rumen bacteria were used to evaluate effects of 100% urea-nitrogen and 75% urea-nitrogen plus 25% amino acid-nitrogen in growth media upon microbial growth rate and yield, specific rate of glucose consumption, and incorporation of glucose into mixed cells, carbon dioxide, and end products. Rumen microbial dry matter, nitrogen, ribonucleic acid, deoxyribonucleic acid, glucose disappearance, and production of volatile fatty acids were considerably higher in medium containing urea plus amino acids as compared with urea only. Specific growth rates of microbes were .104 and .203 and mean doubling times were 6.7 and 3.4 h in the urea and urea plus amino acid growth media. Microbial growth in mg per 100 mg glucose used, per mole glucose and per mole adenosine triphosphate (ATP), and specific rate of glucose consumption in mmol per mg cells-h were 19.3, 34.7, 15.4, and .016 with urea, and 24.4, 44.2, 20.6, and .014 with urea plus amino acids. Percentages of catabolized glucose incorporated into microbial cells, carbon dioxide, and end products did not differ between treatments and averaged 19.5, 7.8, and 64.4%."} {"id": "PMID:1262577", "title": "Dynamics of fermentation of a purified diet and microbial growth in the rumen.", "content": "Ruminal fermentation and disappearance of glucose, starch, and cellulose, and incorporation of glucose and starch into microbial cells were estimated in a fistulated Jersey cow fed twice daily a purified diet containing urea as the sole nitrogen source. Estimated rumen volume was 59.8 liters. Turnover time and rate of passage of rumen contents were 33.4 h and 1.8 liters per h. Turnover times of glucose, starch, and cellulose were .17, 4.7, and 14.2 h. Fermentation times of glucose, starch, and cellulose were .17, 5.5, and 25.1 h. Percentages of glucose, starch, and cellulose utilized in the rumen were 99.4, 85.4, and 60.6. Thus, 18.5% of the carbohydrate fed bypassed rumen fermentation, and 81.5% was utilized in the rumen. All glucose disappeared from the rumen within an hour. An average of 32.1, 43.0, and 14%, respectively, of glucose utilized was incorporated into microbial cells, volatile fatty acids, and carbon dioxide. Percentage of starch incorporated into cells varied, with time being highest 2 h after feeding at 40% and lowest at 20%, 10 h after feeding. Respective percentages of starch incorporated into microbial cells, volatile fatty acids, and carbon dioxide were 32.4, 45.9; and 13.3. Total microbial protein and cell yields per kilogram carbohydrate utilized in the rumen were 77.1 and 117.5 g. Microbial cell yield per mole (estimated) of adenosine triphosphate was 16.2 g.", "contents": "Dynamics of fermentation of a purified diet and microbial growth in the rumen. Ruminal fermentation and disappearance of glucose, starch, and cellulose, and incorporation of glucose and starch into microbial cells were estimated in a fistulated Jersey cow fed twice daily a purified diet containing urea as the sole nitrogen source. Estimated rumen volume was 59.8 liters. Turnover time and rate of passage of rumen contents were 33.4 h and 1.8 liters per h. Turnover times of glucose, starch, and cellulose were .17, 4.7, and 14.2 h. Fermentation times of glucose, starch, and cellulose were .17, 5.5, and 25.1 h. Percentages of glucose, starch, and cellulose utilized in the rumen were 99.4, 85.4, and 60.6. Thus, 18.5% of the carbohydrate fed bypassed rumen fermentation, and 81.5% was utilized in the rumen. All glucose disappeared from the rumen within an hour. An average of 32.1, 43.0, and 14%, respectively, of glucose utilized was incorporated into microbial cells, volatile fatty acids, and carbon dioxide. Percentage of starch incorporated into cells varied, with time being highest 2 h after feeding at 40% and lowest at 20%, 10 h after feeding. Respective percentages of starch incorporated into microbial cells, volatile fatty acids, and carbon dioxide were 32.4, 45.9; and 13.3. Total microbial protein and cell yields per kilogram carbohydrate utilized in the rumen were 77.1 and 117.5 g. Microbial cell yield per mole (estimated) of adenosine triphosphate was 16.2 g."} {"id": "PMID:1262579", "title": "Factors influencing rumen microbial growth rates and yields: effect of amino acid additions to a purified diet with nitrogen from urea.", "content": "Effects of isonitrogenous urea and amino acid additions upon microbial growth in rumen contents from a cow fed a purified diet in which urea was the sole nitrogen source were studied. Incorporation of amino acids into microbial cells, volatile fatty acids, and carbon dioxide was estimated. Rates of microbial growth, volatile fatty acid production, and effects of amino acids upon microbial nitrogen yields were highest right after feeding and decreased with time after feeding. Microbial growth and amounts of amino acids incorporated into microbial cells, volatile fatty acids and carbon dioxide were related closely to quantity of starch remaining in the rumen. High amounts of starch increased microbial protein synthesis from carbon-14 labeled amino acids and reduced amounts of amino acid fermentation. Estimated microbial protein yields per day were 326.0, 444.4, 497.3, and 527.3 g when 0, 15, 30, and 45 mg amino acid nitrogen replaced urea nitrogen during incubation. Respective values for microbial cells per mole estimated adenosine triphosphate were 15.2, 19.2, 21.0, and 24.5. Microbial cell yields per kg carbohydrate digested were 139.0, 189.5, 212.0, and 224.8 g for 0, 15, 30, and 45 mg amino acid nitrogen. Addition of small amounts of amino acids to a diet containing urea as the sole nitrogen source improved considerably rumen microbial protein yields.", "contents": "Factors influencing rumen microbial growth rates and yields: effect of amino acid additions to a purified diet with nitrogen from urea. Effects of isonitrogenous urea and amino acid additions upon microbial growth in rumen contents from a cow fed a purified diet in which urea was the sole nitrogen source were studied. Incorporation of amino acids into microbial cells, volatile fatty acids, and carbon dioxide was estimated. Rates of microbial growth, volatile fatty acid production, and effects of amino acids upon microbial nitrogen yields were highest right after feeding and decreased with time after feeding. Microbial growth and amounts of amino acids incorporated into microbial cells, volatile fatty acids and carbon dioxide were related closely to quantity of starch remaining in the rumen. High amounts of starch increased microbial protein synthesis from carbon-14 labeled amino acids and reduced amounts of amino acid fermentation. Estimated microbial protein yields per day were 326.0, 444.4, 497.3, and 527.3 g when 0, 15, 30, and 45 mg amino acid nitrogen replaced urea nitrogen during incubation. Respective values for microbial cells per mole estimated adenosine triphosphate were 15.2, 19.2, 21.0, and 24.5. Microbial cell yields per kg carbohydrate digested were 139.0, 189.5, 212.0, and 224.8 g for 0, 15, 30, and 45 mg amino acid nitrogen. Addition of small amounts of amino acids to a diet containing urea as the sole nitrogen source improved considerably rumen microbial protein yields."} {"id": "PMID:1262580", "title": "Zinc absorption from the small intestine in young calves.", "content": "Zinc-65 was injected directly into various sites throughout the small intestine of Holstein calves fed a low zinc diet. Zinc absorption was determined by comparing zinc-65 content of blood, liver, kidney, lung, heart, pancreas, rib, muscle, and other tissues. Tissue zinc-65 was plotted against site of injection expressed as percentage of intestinal length from proximal to distal ends. Zinc absorption occurred throughout the small intestine with the amount absorbed per centimeter of length about equal throughout the small intestine. This is in contrast to conclusions from studies of rats indicating more absorption in the proximal part of the small intestine. The difference appears to have been due to artifacts in the procedures with rats. However, species and dietary differences may have affected relative findings between this and earlier work.", "contents": "Zinc absorption from the small intestine in young calves. Zinc-65 was injected directly into various sites throughout the small intestine of Holstein calves fed a low zinc diet. Zinc absorption was determined by comparing zinc-65 content of blood, liver, kidney, lung, heart, pancreas, rib, muscle, and other tissues. Tissue zinc-65 was plotted against site of injection expressed as percentage of intestinal length from proximal to distal ends. Zinc absorption occurred throughout the small intestine with the amount absorbed per centimeter of length about equal throughout the small intestine. This is in contrast to conclusions from studies of rats indicating more absorption in the proximal part of the small intestine. The difference appears to have been due to artifacts in the procedures with rats. However, species and dietary differences may have affected relative findings between this and earlier work."} {"id": "PMID:1262581", "title": "Relationship of testicular weight to age and scrotal circumference of Holstein bulls.", "content": "Testicular weights were recorded for 250 Holstein bulls ranging in age from 19 to 189 mo. The multiple regression equation that best described the relationship between paired-testes weight and age of bull was Y = -368.8 + 952.2 LOG X - 180.3 (log X)2, where Y is paired-testes weight in g and X is bull age in mo. Correlations between these two variables were .86 for 24 bulls less than or equal to 60 mo of age and .60 for 23 greater than 60 mo of age. A linear regression equation for 47 bulls was Y = -645.5 + 34.0 X, where Y is paired-testes weight in g and X is scrotal circumference in cm measured within 1 mo of slaughter. The correlation coefficient was .79. Differences in testicular weights of bulls of similar ages were large. These should be taken into account by measuring scrotal circumference and selecting young bulls with larger testes and superior spermatozoal producing capabilities.", "contents": "Relationship of testicular weight to age and scrotal circumference of Holstein bulls. Testicular weights were recorded for 250 Holstein bulls ranging in age from 19 to 189 mo. The multiple regression equation that best described the relationship between paired-testes weight and age of bull was Y = -368.8 + 952.2 LOG X - 180.3 (log X)2, where Y is paired-testes weight in g and X is bull age in mo. Correlations between these two variables were .86 for 24 bulls less than or equal to 60 mo of age and .60 for 23 greater than 60 mo of age. A linear regression equation for 47 bulls was Y = -645.5 + 34.0 X, where Y is paired-testes weight in g and X is scrotal circumference in cm measured within 1 mo of slaughter. The correlation coefficient was .79. Differences in testicular weights of bulls of similar ages were large. These should be taken into account by measuring scrotal circumference and selecting young bulls with larger testes and superior spermatozoal producing capabilities."} {"id": "PMID:1262582", "title": "Body weight changes in lactating purebred and crossbred dairy cattle.", "content": "Body weights of 396 first and 205 second lactation cows in the first, second, third, and fourth generations of the dairy cattle crossbreeding project at the Illinois Agricultural Experiment Station were studied. Body weights were taken regularly on each animal during the first 9 mo of each lactation with the first weight being taken 3 to 4 days after parturition and subsequent weights at intervals of 30 days thereafter. Among least-squares means there was a decrease in body weight during the first 1 or 2 mo of lactation and a steady increase thereafter in all breed groups for both first and second lactations. There were differences between cows as well as between months for all breed groups in each generation for both lactations. Sums of squares for months were partitioned into linear, quadratic, and cubic components. A third degree polynomial was fitted for each breed group within each generation and separately for each lactation showing the changes in body weights.", "contents": "Body weight changes in lactating purebred and crossbred dairy cattle. Body weights of 396 first and 205 second lactation cows in the first, second, third, and fourth generations of the dairy cattle crossbreeding project at the Illinois Agricultural Experiment Station were studied. Body weights were taken regularly on each animal during the first 9 mo of each lactation with the first weight being taken 3 to 4 days after parturition and subsequent weights at intervals of 30 days thereafter. Among least-squares means there was a decrease in body weight during the first 1 or 2 mo of lactation and a steady increase thereafter in all breed groups for both first and second lactations. There were differences between cows as well as between months for all breed groups in each generation for both lactations. Sums of squares for months were partitioned into linear, quadratic, and cubic components. A third degree polynomial was fitted for each breed group within each generation and separately for each lactation showing the changes in body weights."} {"id": "PMID:1262583", "title": "Bovine plasma corticoids during parturition.", "content": "Concentrations of adrenal corticoids in plasma were determined by a competitive protein-binding technique using jugular blood samples taken three times daily and more frequently during labor from 21 cows before and after parturition. The prepartum value was 6 ng/ml with a sharp rise during the last 16 h before calving. The average value at the time of calving was 19.2 ng/ml with a significant drop 1 h after calving to 11.2 ng/ml and a return to basal concentrations by 3 days postpartum. Evidence that labor is responsible for the increased corticoid is given. Maternal cortisol at calving was correlated with the time taken to calve .23, calf cortisol .04, cow:calf weight ratio -.07, and calf weight .14.", "contents": "Bovine plasma corticoids during parturition. Concentrations of adrenal corticoids in plasma were determined by a competitive protein-binding technique using jugular blood samples taken three times daily and more frequently during labor from 21 cows before and after parturition. The prepartum value was 6 ng/ml with a sharp rise during the last 16 h before calving. The average value at the time of calving was 19.2 ng/ml with a significant drop 1 h after calving to 11.2 ng/ml and a return to basal concentrations by 3 days postpartum. Evidence that labor is responsible for the increased corticoid is given. Maternal cortisol at calving was correlated with the time taken to calve .23, calf cortisol .04, cow:calf weight ratio -.07, and calf weight .14."} {"id": "PMID:1262584", "title": "Fasting heat production in \"lactating\" versus dry dairy cows.", "content": "Fasting heat production was measured 1 and 31 days after lactation ceased in postabsorptive dairy cows varying in daily rate of milk yield just prior to fasting. Daily fasting heat production was higher at 1 than at 31 days, particularly in higher-producing cows. It averaged 100 +/- 3 kilocalories per kilogram body weight-75 31 days after lactation ceased.", "contents": "Fasting heat production in \"lactating\" versus dry dairy cows. Fasting heat production was measured 1 and 31 days after lactation ceased in postabsorptive dairy cows varying in daily rate of milk yield just prior to fasting. Daily fasting heat production was higher at 1 than at 31 days, particularly in higher-producing cows. It averaged 100 +/- 3 kilocalories per kilogram body weight-75 31 days after lactation ceased."} {"id": "PMID:1262585", "title": "Selenium content of feeds and effect of dietary selenium on hair and blood serum.", "content": "A selenium depletion diet (.025 ppm selenium) was fed to two male Holstein calves for its effect on concentrations of selenium in serum. By 90 days, selenium in serum was depressed from .022 ppm to .013 ppm, and one of two calves had died of \"possible white muscle disease.\" Repletion was rapid in that a diet containing .200 ppm selenium increased selenium in serum to .028 ppm within 2 wk. Dietary .280 ppm selenium increased it to .051 ppm in 1 wk. Eleven cows and eleven calves showed averages of .030 ppm in serum (range of .013 to .051 ppm) fed a diet of corn silage (.039 ppm) and supplement (.090 ppm). A sampling of feedstuffs showed a wide range of selenium among feedstuffs (.023 for corn cobs to 2.663 ppm for dried egg albumin) and a wide range within one type feedstuff (shelled corn, .017 to .219 ppm).", "contents": "Selenium content of feeds and effect of dietary selenium on hair and blood serum. A selenium depletion diet (.025 ppm selenium) was fed to two male Holstein calves for its effect on concentrations of selenium in serum. By 90 days, selenium in serum was depressed from .022 ppm to .013 ppm, and one of two calves had died of \"possible white muscle disease.\" Repletion was rapid in that a diet containing .200 ppm selenium increased selenium in serum to .028 ppm within 2 wk. Dietary .280 ppm selenium increased it to .051 ppm in 1 wk. Eleven cows and eleven calves showed averages of .030 ppm in serum (range of .013 to .051 ppm) fed a diet of corn silage (.039 ppm) and supplement (.090 ppm). A sampling of feedstuffs showed a wide range of selenium among feedstuffs (.023 for corn cobs to 2.663 ppm for dried egg albumin) and a wide range within one type feedstuff (shelled corn, .017 to .219 ppm)."} {"id": "PMID:1262606", "title": "Detection of allergy to nuts by the radioallergosorbent test.", "content": "The diagnosis of food allergy is often difficult to make by conventional means. Histories are frequently ambiguous, and skin testing is of dubious reliability because of the number of false-positive and false-negative reactions. We have evaluated the radioallergosorbent test (RAST) for the in vitro measurement of the specific IgE antibodies to nuts, including Brazil nut, almond, walnut, pecan, cashew, and the legume, peanut. Serums were obtained from 18 patients with a history of nut allergy and IgE level and specific IgE antibodies were measured. Thirteen of the 18 patients had significantly elevated IgE antibody (greater than twice control) to one or more of the allergens. Prausnitz-K\u00fcstner tests on selected serums in general corroborated the results of the in vitro studies. Five patients had RAST elevations to 2 or more nuts. As a group RAST-positive patients had elevated mean serum IgE levels and more severe clinical symptoms (p less than 0.01). The specificity and cross-reactivity of IgE antibodies to different nut antigens was investigated by RAST inhibition with serums from 5 patients having high levels of IgE antibody. In 4 patients no cross-reactivity between Brazil nut and peanut was found. In contrast, several nut extracts inhibited the reaction of pecan allergen with IgE antibodies. These results indicate that specific IgE antibodies can be measured by RAST in patients with nut allergy and the cross-reactivity of nut antigens can be investigated. RAST would appear to be most useful in confirming the diagnosis of nut hypersensitivity in children or in highly allergic patients in whom skin testing poses a risk of anaphylaxis.", "contents": "Detection of allergy to nuts by the radioallergosorbent test. The diagnosis of food allergy is often difficult to make by conventional means. Histories are frequently ambiguous, and skin testing is of dubious reliability because of the number of false-positive and false-negative reactions. We have evaluated the radioallergosorbent test (RAST) for the in vitro measurement of the specific IgE antibodies to nuts, including Brazil nut, almond, walnut, pecan, cashew, and the legume, peanut. Serums were obtained from 18 patients with a history of nut allergy and IgE level and specific IgE antibodies were measured. Thirteen of the 18 patients had significantly elevated IgE antibody (greater than twice control) to one or more of the allergens. Prausnitz-K\u00fcstner tests on selected serums in general corroborated the results of the in vitro studies. Five patients had RAST elevations to 2 or more nuts. As a group RAST-positive patients had elevated mean serum IgE levels and more severe clinical symptoms (p less than 0.01). The specificity and cross-reactivity of IgE antibodies to different nut antigens was investigated by RAST inhibition with serums from 5 patients having high levels of IgE antibody. In 4 patients no cross-reactivity between Brazil nut and peanut was found. In contrast, several nut extracts inhibited the reaction of pecan allergen with IgE antibodies. These results indicate that specific IgE antibodies can be measured by RAST in patients with nut allergy and the cross-reactivity of nut antigens can be investigated. RAST would appear to be most useful in confirming the diagnosis of nut hypersensitivity in children or in highly allergic patients in whom skin testing poses a risk of anaphylaxis."} {"id": "PMID:1262607", "title": "The occurrence of arrhythmias in hospitalized asthmatic patients.", "content": "Twenty-four hour continuous ECG monitoring was performed on 20 patients hospitalized for asthma to evaluate the occurrence of potentially dangerous arrhythmias. Most patients (19/20) had sinus tachycardia on admission; premature ventricular contractions (PVCs) were present in 4; 1 had angina associated with runs of increased sinus tachycardia. With improvement in PaO2 and FEV1, the heart rate decreased in 17 patients and fewer PVCs were present in 2. Arrhythmias were not a serious problem in the patients studied.", "contents": "The occurrence of arrhythmias in hospitalized asthmatic patients. Twenty-four hour continuous ECG monitoring was performed on 20 patients hospitalized for asthma to evaluate the occurrence of potentially dangerous arrhythmias. Most patients (19/20) had sinus tachycardia on admission; premature ventricular contractions (PVCs) were present in 4; 1 had angina associated with runs of increased sinus tachycardia. With improvement in PaO2 and FEV1, the heart rate decreased in 17 patients and fewer PVCs were present in 2. Arrhythmias were not a serious problem in the patients studied."} {"id": "PMID:1262608", "title": "Activation of the complement sequence by extracts of bacteria and fungi associated with hypersensitivity pneumonitis.", "content": "Complement (C) consumption by antigens associated with hypersensitivity pneumonitis was investigated. Micropolyspora faeni in the presence of precipitating antibodies consumed C in a manner similar to the BSA-anti BSA system. An extract of M. faeni was shown to consume C and convert C3PA to C3A in the absence of detectable antibodies. In addition, three species of Aspergillus and two strains of Thermoactinomyces vulgaris were also shown to have the same activity with respect to C3PA. Mucor racemosus, Hormodendrum sp. and a mixed extract of Penicillium did not convert C3PA.", "contents": "Activation of the complement sequence by extracts of bacteria and fungi associated with hypersensitivity pneumonitis. Complement (C) consumption by antigens associated with hypersensitivity pneumonitis was investigated. Micropolyspora faeni in the presence of precipitating antibodies consumed C in a manner similar to the BSA-anti BSA system. An extract of M. faeni was shown to consume C and convert C3PA to C3A in the absence of detectable antibodies. In addition, three species of Aspergillus and two strains of Thermoactinomyces vulgaris were also shown to have the same activity with respect to C3PA. Mucor racemosus, Hormodendrum sp. and a mixed extract of Penicillium did not convert C3PA."} {"id": "PMID:1262609", "title": "Median age at onset of asthma and allergic rhinitis in Tecumseh, Michigan.", "content": "The ages at which allergies are likely to first become manifest is a subject of epidemiologic interest. The distribution of the onset ages reported in a population survey provides a distorted picture because it is a function of the age distribution of the population at the time of survey, and hence does not represent generational experience. A lifetable method is presented which transforms the raw cross-sectional data to a longitudinal basis. The information on onset age of asthma and allergic rhinitis collected in the 1962-1965 cycle of the Tecumseh Community Health Study is used to illustrate the method. The resultant distributions have median onset ages for the respective allergies which are considerably higher than those based on the onset frequency distributions of enumerated data.", "contents": "Median age at onset of asthma and allergic rhinitis in Tecumseh, Michigan. The ages at which allergies are likely to first become manifest is a subject of epidemiologic interest. The distribution of the onset ages reported in a population survey provides a distorted picture because it is a function of the age distribution of the population at the time of survey, and hence does not represent generational experience. A lifetable method is presented which transforms the raw cross-sectional data to a longitudinal basis. The information on onset age of asthma and allergic rhinitis collected in the 1962-1965 cycle of the Tecumseh Community Health Study is used to illustrate the method. The resultant distributions have median onset ages for the respective allergies which are considerably higher than those based on the onset frequency distributions of enumerated data."} {"id": "PMID:1262610", "title": "Wood dust hypersensitivity.", "content": "Two patients developed severe respiratory difficulty after occupational exposure to sawdust derived from abiruana wood. Both patients had positive immediate wheal-and-flare responses to skin tests with an extract of abiruana wood. Skin tests to other wood dusts were negative. Precipitating antibodies could not be demonstrated in the patients' serum. Bronchial challenge in both patients produced acute airway obstruction that was rapidly reversible. In addition, 1 patient developed airway obstruction 6-8 hr later that was more gradually reversible.", "contents": "Wood dust hypersensitivity. Two patients developed severe respiratory difficulty after occupational exposure to sawdust derived from abiruana wood. Both patients had positive immediate wheal-and-flare responses to skin tests with an extract of abiruana wood. Skin tests to other wood dusts were negative. Precipitating antibodies could not be demonstrated in the patients' serum. Bronchial challenge in both patients produced acute airway obstruction that was rapidly reversible. In addition, 1 patient developed airway obstruction 6-8 hr later that was more gradually reversible."} {"id": "PMID:1262611", "title": "Egg allergy, influenza vaccine, and immunoglobulin E antibody.", "content": "In a study of 70 patients with asthma, rhinitis, and eczema, those giving a definite history of allergic reactions to egg more frequently showed positive skin tests to egg extracts (p = less than 0.003), the wheal diameters of which were significantly larger (p = less than 0.01) than in patients with only a possible or no such history. Patients with a definite history of egg allergy had significantly higher levels of specific IgE antibody against egg yolk, egg white, and allantoic fluid than patients in the other two groups (p = less than 0.005). Seven patients, all of whom had given a definite history of allergy to egg, were found to have positive skin prick tests to influenza vaccine, at the concentration used in medical practice. Two of these patients had previously been given influenza vaccine and both had developed adverse reactions. Of the 22 patients giving a definite history of allergy to egg, the 7 (35 per cent) with positive skin tests to influenza vaccine had significantly larger skin tests and higher levels of specific IgE antibody to the egg extracts than the group as a whole (p = less than 0.001). Allergic reactions to influenza vaccine are likely to occur in patients who have a definite history of allergy to egg and large skin prick test reactions or high levels of specific IgE antibody to egg extracts. Those at risk can best be identified by skin prick testing with egg extracts and undiluted influenza vaccine.", "contents": "Egg allergy, influenza vaccine, and immunoglobulin E antibody. In a study of 70 patients with asthma, rhinitis, and eczema, those giving a definite history of allergic reactions to egg more frequently showed positive skin tests to egg extracts (p = less than 0.003), the wheal diameters of which were significantly larger (p = less than 0.01) than in patients with only a possible or no such history. Patients with a definite history of egg allergy had significantly higher levels of specific IgE antibody against egg yolk, egg white, and allantoic fluid than patients in the other two groups (p = less than 0.005). Seven patients, all of whom had given a definite history of allergy to egg, were found to have positive skin prick tests to influenza vaccine, at the concentration used in medical practice. Two of these patients had previously been given influenza vaccine and both had developed adverse reactions. Of the 22 patients giving a definite history of allergy to egg, the 7 (35 per cent) with positive skin tests to influenza vaccine had significantly larger skin tests and higher levels of specific IgE antibody to the egg extracts than the group as a whole (p = less than 0.001). Allergic reactions to influenza vaccine are likely to occur in patients who have a definite history of allergy to egg and large skin prick test reactions or high levels of specific IgE antibody to egg extracts. Those at risk can best be identified by skin prick testing with egg extracts and undiluted influenza vaccine."} {"id": "PMID:1262612", "title": "Competent cellular immunity in allergic rhinitis patients with elevated IgE.", "content": "Parameters of cell-mediated immunity (CMI) were studied in 17 allergic rhinitis patients selected for markedly elevated total serum IgE levels (greater than 300 IU/ml) and 14 normal controls. Mean serum IgE levels were 1,421 IU/ml and 101 IU/ml in the allergic and control groups, respectively (p less than 0.001). There were no significant differences between the allergic patients and the normal controls in delayed cutaneous hypersensitivity, in mitogen and antigen lymphocyte transformation in heterologous or autologous plasma, or in percentage of sheep erythrocyte rosettes. The allergic patient group had a significantly higher percentage of sheep erythrocyte-antibody-complement rosettes (p less than 0.05). Markedly elevated total serum IgE levels in allergic rhinitis patients were not associated with any detectable impairment of CMI.", "contents": "Competent cellular immunity in allergic rhinitis patients with elevated IgE. Parameters of cell-mediated immunity (CMI) were studied in 17 allergic rhinitis patients selected for markedly elevated total serum IgE levels (greater than 300 IU/ml) and 14 normal controls. Mean serum IgE levels were 1,421 IU/ml and 101 IU/ml in the allergic and control groups, respectively (p less than 0.001). There were no significant differences between the allergic patients and the normal controls in delayed cutaneous hypersensitivity, in mitogen and antigen lymphocyte transformation in heterologous or autologous plasma, or in percentage of sheep erythrocyte rosettes. The allergic patient group had a significantly higher percentage of sheep erythrocyte-antibody-complement rosettes (p less than 0.05). Markedly elevated total serum IgE levels in allergic rhinitis patients were not associated with any detectable impairment of CMI."} {"id": "PMID:1262613", "title": "Effect of treadmill exercise on asthmatic children.", "content": "Measurement of peak expiratory flow rate before and after treadmill walking repeated at hourly intervals in asthmatic children disclosed progressive decreases in exercise-induced asthma. Treadmill running was followed by more extreme excercise-induced bronchospasm than treadmill walking. Exercise-induced asthma occurred in some children whose heart rates did not reach 160 during treadmill exercise, and heart rate during exercise was not correlated with the extent of exercise-induced bronchospasm.", "contents": "Effect of treadmill exercise on asthmatic children. Measurement of peak expiratory flow rate before and after treadmill walking repeated at hourly intervals in asthmatic children disclosed progressive decreases in exercise-induced asthma. Treadmill running was followed by more extreme excercise-induced bronchospasm than treadmill walking. Exercise-induced asthma occurred in some children whose heart rates did not reach 160 during treadmill exercise, and heart rate during exercise was not correlated with the extent of exercise-induced bronchospasm."} {"id": "PMID:1262614", "title": "Properties of mouse homocytotropic and heterocytotropic antibodies.", "content": "Mouse antisera were analyzed for the presence of homocytotropic and heterocytotropic antibodies. Two distinct populations of antibodies were detected by the homologous passive cutaneous anaphylaxis (PCA) reaction. The first was active 2 hr after injection, heat-stable, and partially reactive with antisera to mouse IgG1. The second was active 48 hr after injection, was heat-labile, and probably belonged to the IgE class of mouse immunoglobulins. In addition, it was demonstrated that there were also two antibodies active in the heterologous PCA reaction in rats, a heat-stable antibody and a heat=labile antibody. Contrary to results obtained with homocytotropic antibodies, none of the heterocytotropic antibodies detected reacted with antisera to mouse IgG1 or IgG2. These studies suggest that in addition to IgE there may exist another heterocytotropic antibody in mouse antisera and that caution should be employed when using the 2-hr PCA reaction in the rat as a sole criterion for detection of mouse IgE.", "contents": "Properties of mouse homocytotropic and heterocytotropic antibodies. Mouse antisera were analyzed for the presence of homocytotropic and heterocytotropic antibodies. Two distinct populations of antibodies were detected by the homologous passive cutaneous anaphylaxis (PCA) reaction. The first was active 2 hr after injection, heat-stable, and partially reactive with antisera to mouse IgG1. The second was active 48 hr after injection, was heat-labile, and probably belonged to the IgE class of mouse immunoglobulins. In addition, it was demonstrated that there were also two antibodies active in the heterologous PCA reaction in rats, a heat-stable antibody and a heat=labile antibody. Contrary to results obtained with homocytotropic antibodies, none of the heterocytotropic antibodies detected reacted with antisera to mouse IgG1 or IgG2. These studies suggest that in addition to IgE there may exist another heterocytotropic antibody in mouse antisera and that caution should be employed when using the 2-hr PCA reaction in the rat as a sole criterion for detection of mouse IgE."} {"id": "PMID:1262615", "title": "Allergenicity and immunogenicity of Basidiomycetes.", "content": "Species selected from six families of the class Basidiomycetes were evaluated for allergenicity in atopic and nonatopic individuals and for immunogenicity and antigenic cross-reactivity in experimental animals. Between 42% and 68% of atopic asthmatics demonstrated positive Type 1 wheal-and-flare skin reactivity to basidiomycete metabolic and somatic antigens. Sixty-four percent of skin test-positive atopic asthmatics exhibited positive RAST to as basidiomycete metabolic antigen and 50% were positive to somatic antigen. Negative RAST results were obtained in all nonatopic control sera. Only an occasional individual demonstrated positive serum antibasidiomycete precipitins by counterimmunoelectrophoresis. All basidiomycete species studied were highly immunogenic in the rabbit and most appeared to contain an electrophoretically heterogenous group of antigens with predominant anodal mobility. Ouchterlony double-diffusion analysis employing hyperimmune rabbit antisera indicated the presence of shared antigens among all basidiomycete species with the exception of Pleurotus. Rabbit antibasidiomycete sera did not cross-react with antigens of several common species of the Fungi imperfecti. Results indicate that many atopic asthmatics of the Gulf South area demonstrate IgE-medicated hypersensitivity to basidiomycete antigens as evidenced by positive wheal-and-flare skin reactivity and/or RAST. Basidiomycetes are also immunogenic in the rabbit and possess antigens that do not cross-react with those of certain Fungi imperfecti.", "contents": "Allergenicity and immunogenicity of Basidiomycetes. Species selected from six families of the class Basidiomycetes were evaluated for allergenicity in atopic and nonatopic individuals and for immunogenicity and antigenic cross-reactivity in experimental animals. Between 42% and 68% of atopic asthmatics demonstrated positive Type 1 wheal-and-flare skin reactivity to basidiomycete metabolic and somatic antigens. Sixty-four percent of skin test-positive atopic asthmatics exhibited positive RAST to as basidiomycete metabolic antigen and 50% were positive to somatic antigen. Negative RAST results were obtained in all nonatopic control sera. Only an occasional individual demonstrated positive serum antibasidiomycete precipitins by counterimmunoelectrophoresis. All basidiomycete species studied were highly immunogenic in the rabbit and most appeared to contain an electrophoretically heterogenous group of antigens with predominant anodal mobility. Ouchterlony double-diffusion analysis employing hyperimmune rabbit antisera indicated the presence of shared antigens among all basidiomycete species with the exception of Pleurotus. Rabbit antibasidiomycete sera did not cross-react with antigens of several common species of the Fungi imperfecti. Results indicate that many atopic asthmatics of the Gulf South area demonstrate IgE-medicated hypersensitivity to basidiomycete antigens as evidenced by positive wheal-and-flare skin reactivity and/or RAST. Basidiomycetes are also immunogenic in the rabbit and possess antigens that do not cross-react with those of certain Fungi imperfecti."} {"id": "PMID:1262616", "title": "Possible asbestos hazards in clinical allergy.", "content": "The potential hazards of biological products contaminated by asbestos fibers are quite properly being reviewed by the food and pharmaceutical industries. We have demonstrated that glycerinated saline solutions can be contaminated with asbestos fibers under certain conditions of simulated clinical use of asbestos-packed syringes. Because the fibrogenic and carcinogenic effects of asbestos are subtle and may not be manifest for a long latent period, the future use of asbestos containing materials in allergy practice might be more harmful than now realized.", "contents": "Possible asbestos hazards in clinical allergy. The potential hazards of biological products contaminated by asbestos fibers are quite properly being reviewed by the food and pharmaceutical industries. We have demonstrated that glycerinated saline solutions can be contaminated with asbestos fibers under certain conditions of simulated clinical use of asbestos-packed syringes. Because the fibrogenic and carcinogenic effects of asbestos are subtle and may not be manifest for a long latent period, the future use of asbestos containing materials in allergy practice might be more harmful than now realized."} {"id": "PMID:1262665", "title": "Changing patterns of professional education in colleges and universities--1964 and 1974. Survey in the North Atlantic Region.", "content": "This report concerns two surveys of undergraduate nutrition education in a selected group of degree-granting institutions within the North Atlantic Region of the United States. The purpose of the surveys was to determine the status of nutrition teaching in the early 1960s and the direction of change during the intervening ten-year period (1974). Reviews of the literature and college catalogues, personal interivews, letters of inquiry, and questionaires formed the basis for study. The last decade has witnessed change in organizational arrangement and in the number of programs offering major concentrations in foods, nutrition, and dietetics. Of these, twelve units in the Region studied are now engaged in coordinated programming. There has been a 125 per cent increase in foods and nutrition faculty. All but seventeen of the 275 faculty appear in programs approved by The American Dietetic Association. Basic questions about undergraduate education in foods and nutrition and the most desirable administrative structure for this specialization will continue through the 1970s. Solutions will undoubtedly be forthcoming after further experimentation and evaluative research.", "contents": "Changing patterns of professional education in colleges and universities--1964 and 1974. Survey in the North Atlantic Region. This report concerns two surveys of undergraduate nutrition education in a selected group of degree-granting institutions within the North Atlantic Region of the United States. The purpose of the surveys was to determine the status of nutrition teaching in the early 1960s and the direction of change during the intervening ten-year period (1974). Reviews of the literature and college catalogues, personal interivews, letters of inquiry, and questionaires formed the basis for study. The last decade has witnessed change in organizational arrangement and in the number of programs offering major concentrations in foods, nutrition, and dietetics. Of these, twelve units in the Region studied are now engaged in coordinated programming. There has been a 125 per cent increase in foods and nutrition faculty. All but seventeen of the 275 faculty appear in programs approved by The American Dietetic Association. Basic questions about undergraduate education in foods and nutrition and the most desirable administrative structure for this specialization will continue through the 1970s. Solutions will undoubtedly be forthcoming after further experimentation and evaluative research."} {"id": "PMID:1262666", "title": "Development of a rating scale to measure learning in clinical dietetics. I. Theoretical considerations and method of construction.", "content": "The trend to introduce earlier clinical experience in dietetic education requires that attention be directed toward evaluation of learning of such clinical skills as communication and interpersonal relations. Some of the theoretical factors associated with clinical evaluation are discussed, and a method is described for developing a rating scale to measure learning in an intoductory clinical course in dietetics. The method involved: (a) analysis of course objectives to determine the general areas of learning which were appropriate and valid to measure in the clinical environment; (b) specification of observable and one-dimensional behaviors seen as componets of the overall objectives; and (c) concise definition of the rating continuum. Specific attention was directed toward constructing an instrument which could be used to counsel students as well as provide information for determining grades. Preliminary trials indicated the instrument to be practical, reliable, objective, and valid to measure clinical learning.", "contents": "Development of a rating scale to measure learning in clinical dietetics. I. Theoretical considerations and method of construction. The trend to introduce earlier clinical experience in dietetic education requires that attention be directed toward evaluation of learning of such clinical skills as communication and interpersonal relations. Some of the theoretical factors associated with clinical evaluation are discussed, and a method is described for developing a rating scale to measure learning in an intoductory clinical course in dietetics. The method involved: (a) analysis of course objectives to determine the general areas of learning which were appropriate and valid to measure in the clinical environment; (b) specification of observable and one-dimensional behaviors seen as componets of the overall objectives; and (c) concise definition of the rating continuum. Specific attention was directed toward constructing an instrument which could be used to counsel students as well as provide information for determining grades. Preliminary trials indicated the instrument to be practical, reliable, objective, and valid to measure clinical learning."} {"id": "PMID:1262667", "title": "Development of a rating scale to measure learning in clinical dietetics. II. Pilot test.", "content": "When the instrument was pilot tested under actual conditions of a clinical course, it was found practical to use, provided the raters were sufficiently trained and were aware of the logistical problems that might occur. A consensus of both students and raters reaffirmed that the formative properties of the instrument were of value in student counseling, and the rating of students during each clinical session should continue. The objectivity of the instrument also appeared to be sufficient to allow summative grading of students without large differences of opinion within pairs of raters. Measurement of intra-rater reliability was not attempted. The investigators feel that any future study with the instrument should include this analysis. The process of construction and testing reported here appears to be useful in developing a rating scale to measure learning in clinical dietetics.", "contents": "Development of a rating scale to measure learning in clinical dietetics. II. Pilot test. When the instrument was pilot tested under actual conditions of a clinical course, it was found practical to use, provided the raters were sufficiently trained and were aware of the logistical problems that might occur. A consensus of both students and raters reaffirmed that the formative properties of the instrument were of value in student counseling, and the rating of students during each clinical session should continue. The objectivity of the instrument also appeared to be sufficient to allow summative grading of students without large differences of opinion within pairs of raters. Measurement of intra-rater reliability was not attempted. The investigators feel that any future study with the instrument should include this analysis. The process of construction and testing reported here appears to be useful in developing a rating scale to measure learning in clinical dietetics."} {"id": "PMID:1262668", "title": "Design and use of an instrument to evaluate students' clinical performance.", "content": "An instrument for evaluating clinical performance of students was developed for the coordinated undergraduate program in dietetics at The Ohio State University. The development and evaluation of the instrument are described. Statistical data show a significant degree of correlation among three evaluators: the student, his preceptor, and faculty. In addition, use of the instrument facilitated evaluation, and students responded favorably to criterion-referenced rather than to norm-referenced evaluation conferences.", "contents": "Design and use of an instrument to evaluate students' clinical performance. An instrument for evaluating clinical performance of students was developed for the coordinated undergraduate program in dietetics at The Ohio State University. The development and evaluation of the instrument are described. Statistical data show a significant degree of correlation among three evaluators: the student, his preceptor, and faculty. In addition, use of the instrument facilitated evaluation, and students responded favorably to criterion-referenced rather than to norm-referenced evaluation conferences."} {"id": "PMID:1262669", "title": "Nutritional knowledge and attitudes of registered nurses.", "content": "Nutritional knowledge and attitudes of hospital nurses in Nebraska and their perceptions of the role of the dietitian in patient care were studied. In general, they had favorable attitudes toward nutrition. Although their knowledge was adequate, they lacked confidence in that knowledge. The nurses perceived dietitians in an educational rather than a service role. Older nurses had more favorable attitudes but were less knowledgeable than younger ones. More knowledgeable nurses had more positive attitudes toward their own role in nutrition education and toward the team approach to health care.", "contents": "Nutritional knowledge and attitudes of registered nurses. Nutritional knowledge and attitudes of hospital nurses in Nebraska and their perceptions of the role of the dietitian in patient care were studied. In general, they had favorable attitudes toward nutrition. Although their knowledge was adequate, they lacked confidence in that knowledge. The nurses perceived dietitians in an educational rather than a service role. Older nurses had more favorable attitudes but were less knowledgeable than younger ones. More knowledgeable nurses had more positive attitudes toward their own role in nutrition education and toward the team approach to health care."} {"id": "PMID:1262670", "title": "Developing a demand forecasting system for a foodservice operation.", "content": "In foodservice operations, accurate and dependable forecasts of food production demands can help control food and labor costs. A decreased incidence of menu item over- and under-production should lower scheduled labor and production time and optimize use of equipment. Each foodservice system has specified characteristics and patterns of activity. A procedure to develop, establish, control, and evaluate a forecasting system is described. The objectives of the foodservice and the proposed forecasting system must be defined. A cycle menu and historical data bases are two key inputs. It is more accurate to forecast menu item demand than diet category demand because of the complexity in categorizing multi-restricted diets. Control of the system is maintained by establishing policies and procedures and conducting routine subjective and objective evaluations.", "contents": "Developing a demand forecasting system for a foodservice operation. In foodservice operations, accurate and dependable forecasts of food production demands can help control food and labor costs. A decreased incidence of menu item over- and under-production should lower scheduled labor and production time and optimize use of equipment. Each foodservice system has specified characteristics and patterns of activity. A procedure to develop, establish, control, and evaluate a forecasting system is described. The objectives of the foodservice and the proposed forecasting system must be defined. A cycle menu and historical data bases are two key inputs. It is more accurate to forecast menu item demand than diet category demand because of the complexity in categorizing multi-restricted diets. Control of the system is maintained by establishing policies and procedures and conducting routine subjective and objective evaluations."} {"id": "PMID:1262673", "title": "A weight control program for students using diet and behavior therapy.", "content": "A twelve-week weight-reducing program for students was conducted at the University of Kentucky. The program, which was developed and directed by graduate students in nutrition, utilized a combination of behavior therapy and diet therapy. Initiated in the spring of 1975, the program has been continued in the 1975-76 year. All students completing the program achieved weight reduction. Their weight losses averaged 2/3 lb. a week. The dropout rate for the program was 40 per cent. One-third of the participants completing the program reached their weight-reduction goals. These results suggest that further attempts should be made to improve weight-reducing suitable for college students.", "contents": "A weight control program for students using diet and behavior therapy. A twelve-week weight-reducing program for students was conducted at the University of Kentucky. The program, which was developed and directed by graduate students in nutrition, utilized a combination of behavior therapy and diet therapy. Initiated in the spring of 1975, the program has been continued in the 1975-76 year. All students completing the program achieved weight reduction. Their weight losses averaged 2/3 lb. a week. The dropout rate for the program was 40 per cent. One-third of the participants completing the program reached their weight-reduction goals. These results suggest that further attempts should be made to improve weight-reducing suitable for college students."} {"id": "PMID:1262674", "title": "Progeria: autopsy report of one case, with a review of pathologic findings reported in the literature.", "content": "An autopsy case of progeria associated with elastotic degeneration of the skin and preservation of the scalp hair, in a 20-year-old woman, is presented. The pathologic findings were scleroderma-like skin atrophy, elastotic degeneration of the skin, arteriosclerosis, atrophy of the endocrine glands, and acute peritonitis after appendectomy. In the reported cases of progeria, as in Werner's syndrome, no responsible parenchymatous organ has been identified. Rather, connective tissue, widely distributed throughout the entire body, may play an important role. The possible abnormal metabolism of connective tissue in progeria deserves further study.", "contents": "Progeria: autopsy report of one case, with a review of pathologic findings reported in the literature. An autopsy case of progeria associated with elastotic degeneration of the skin and preservation of the scalp hair, in a 20-year-old woman, is presented. The pathologic findings were scleroderma-like skin atrophy, elastotic degeneration of the skin, arteriosclerosis, atrophy of the endocrine glands, and acute peritonitis after appendectomy. In the reported cases of progeria, as in Werner's syndrome, no responsible parenchymatous organ has been identified. Rather, connective tissue, widely distributed throughout the entire body, may play an important role. The possible abnormal metabolism of connective tissue in progeria deserves further study."} {"id": "PMID:1262675", "title": "Free radical theory of aging: inhibition of amyloidosis in mice by antioxidants; possible mechanism.", "content": "The antioxidants, alpha-tocopherol acetate and a quinolone derivative (Santoquin), inhibited the development of amyloidosis when added to the diet of casein-injected C3HeB/FeJ male mice. Santoquin, and to a lesser extent butylated hydroxytoluene (BHT), also depressed the appearance of a plasma protein fraction in these mice; the effect of alpha-tocopherol was not determined. Consideration of the current knowledge of amyloid, in the light of these antioxidant studies, prompted the following hypothesis. Amyloidosis is largely the result of an enhanced rate of oxidative degradation of a connective-tissue glycoprotein(s) coupled with oxidative/enzymatic changes in the plasma, both of the tissue-derived substances and of immunoglobulins, to form the amyloid fibril protein subunits (AL and AA) which subsequently aggreagate to form the amyloid fibrils.", "contents": "Free radical theory of aging: inhibition of amyloidosis in mice by antioxidants; possible mechanism. The antioxidants, alpha-tocopherol acetate and a quinolone derivative (Santoquin), inhibited the development of amyloidosis when added to the diet of casein-injected C3HeB/FeJ male mice. Santoquin, and to a lesser extent butylated hydroxytoluene (BHT), also depressed the appearance of a plasma protein fraction in these mice; the effect of alpha-tocopherol was not determined. Consideration of the current knowledge of amyloid, in the light of these antioxidant studies, prompted the following hypothesis. Amyloidosis is largely the result of an enhanced rate of oxidative degradation of a connective-tissue glycoprotein(s) coupled with oxidative/enzymatic changes in the plasma, both of the tissue-derived substances and of immunoglobulins, to form the amyloid fibril protein subunits (AL and AA) which subsequently aggreagate to form the amyloid fibrils."} {"id": "PMID:1262676", "title": "Comparison of two systems for stroke rehabilitation in a general hospital.", "content": "This study was designed to compare the effectiveness of stroke rehabilitation therapy in a specialized Stroke Unit with that provided on the medical service of a general hospital (Rhode Island Hospital). The 8-bed Stroke Unit is staffed by a multidisciplinary team, and a weekly conference is held for evaluation and planning. On the basis of data obtained from the hospital records, two groups of patients were studied: 224 who were treated in the Stroke Unit, and 110 who were evaluated and approved for admission to the Unit but were not accommodated. A rigid \"first come, first served\" policy for admission to the Unit was observed. Hypothesis testing was performed with reference to the patient's medical condition, socioeconomic status, demographic characteristics, and difficulties during hospital stay to determine whether the groups were comparable. A patient was considered to have improved if his condition decreased in severity between the time of admission to therapy and the time of discharge. Severity was rated as: mild (level one), moderate (level two), severe (level three), and profound (level four). No significant difference in rehabilitation results was found between the two treatment systems at severity levels two (moderate) and four (profound). However, the Stroke Unit attained significantly better results with level-three patients (severe stroke). This group received more sessions of physical therapy and remained in the hospital longer than did the level-three patients treated on the general medical service. Physicians referred patients selectively to the Stroke Unit, althoug the Unit had no policy of screening patients for admission, and this may have had some influence on the achievement of better results with level-three patients. Level-four patients did not do well in either setting.", "contents": "Comparison of two systems for stroke rehabilitation in a general hospital. This study was designed to compare the effectiveness of stroke rehabilitation therapy in a specialized Stroke Unit with that provided on the medical service of a general hospital (Rhode Island Hospital). The 8-bed Stroke Unit is staffed by a multidisciplinary team, and a weekly conference is held for evaluation and planning. On the basis of data obtained from the hospital records, two groups of patients were studied: 224 who were treated in the Stroke Unit, and 110 who were evaluated and approved for admission to the Unit but were not accommodated. A rigid \"first come, first served\" policy for admission to the Unit was observed. Hypothesis testing was performed with reference to the patient's medical condition, socioeconomic status, demographic characteristics, and difficulties during hospital stay to determine whether the groups were comparable. A patient was considered to have improved if his condition decreased in severity between the time of admission to therapy and the time of discharge. Severity was rated as: mild (level one), moderate (level two), severe (level three), and profound (level four). No significant difference in rehabilitation results was found between the two treatment systems at severity levels two (moderate) and four (profound). However, the Stroke Unit attained significantly better results with level-three patients (severe stroke). This group received more sessions of physical therapy and remained in the hospital longer than did the level-three patients treated on the general medical service. Physicians referred patients selectively to the Stroke Unit, althoug the Unit had no policy of screening patients for admission, and this may have had some influence on the achievement of better results with level-three patients. Level-four patients did not do well in either setting."} {"id": "PMID:1262677", "title": "The care of decubitus ulcers pressure sores.", "content": "Despite a large volume of literature particularly directed toward treatment, pressure sores (including decubitus ulcers) remain a difficult problem, especially in the nursing home environment. The treatment of pressure sores is somewhat controversial and quite diversified. Selection of a successful therapeutic modality must be preceded by correct evaluation, i.e., whether the sore is superficial or deep, open or closed. The treatment of superficial sores is conservative and directed toward cleanliness, relief of pressure, and exposure to air. Surgical debridement may be indicated. Proteolytic enzymes often are employed as adjunctive therapy, although there are some major drawbacks to their use. The plethora of therapeutic agents suggested for the treatment of deep pressure sores probably is related to the difficulties in achieving success. Surgical debridement is indicated, and proteolytic enzymes are widely used. Possible interactions. and factors leading to the inactivation of these enzymes are discussed, as is the use of various solutions, ointments, gold leaf, oxygen, dry heat, and other adjunctive devices. Of paramount importance in the management of pressure sores is the maintenance of cleanliness and dryness.", "contents": "The care of decubitus ulcers pressure sores. Despite a large volume of literature particularly directed toward treatment, pressure sores (including decubitus ulcers) remain a difficult problem, especially in the nursing home environment. The treatment of pressure sores is somewhat controversial and quite diversified. Selection of a successful therapeutic modality must be preceded by correct evaluation, i.e., whether the sore is superficial or deep, open or closed. The treatment of superficial sores is conservative and directed toward cleanliness, relief of pressure, and exposure to air. Surgical debridement may be indicated. Proteolytic enzymes often are employed as adjunctive therapy, although there are some major drawbacks to their use. The plethora of therapeutic agents suggested for the treatment of deep pressure sores probably is related to the difficulties in achieving success. Surgical debridement is indicated, and proteolytic enzymes are widely used. Possible interactions. and factors leading to the inactivation of these enzymes are discussed, as is the use of various solutions, ointments, gold leaf, oxygen, dry heat, and other adjunctive devices. Of paramount importance in the management of pressure sores is the maintenance of cleanliness and dryness."} {"id": "PMID:1262678", "title": "Myasthenia gravis in the elderly.", "content": "During a 15-year period in Jerusalem, myasthenia gravis was diagnosed in 15 patients aged 60 or older. At this age, diagnosis is difficult because of such possible associated conditions as cerebrovascular and cardiovascular arteriosclerotic diseases or bronchopulmonary disorders. The clinical course often is complicated by these associated conditions, and also by their treatment. Seven of the patients died within 4 years of the onset of their illness, but only 5 because of myasthenia gravis. This disease represents an important diagnostic and therapeutic problem in elderly patients.", "contents": "Myasthenia gravis in the elderly. During a 15-year period in Jerusalem, myasthenia gravis was diagnosed in 15 patients aged 60 or older. At this age, diagnosis is difficult because of such possible associated conditions as cerebrovascular and cardiovascular arteriosclerotic diseases or bronchopulmonary disorders. The clinical course often is complicated by these associated conditions, and also by their treatment. Seven of the patients died within 4 years of the onset of their illness, but only 5 because of myasthenia gravis. This disease represents an important diagnostic and therapeutic problem in elderly patients."} {"id": "PMID:1262686", "title": "Immunisation of sheep against Schistosoma mattheei using either irradiated cercariae or irradiated schistosomula.", "content": "Irradiated cercariae, irradiated schistosomula, or heterologous infections were used to vaccinate sheep against Schistosoma mattheei infection. In the first experiment four doses of 10(4) S. mattheei cercariae irradiated at 6Kr were administered to sheep by percutaneous infection at 4 week intervals. This induced a 74% reduction in a challenge infection compared to control sheep while only 13% protection was achieved in a third group of sheep immunised with normal cercariae of the heterologous parasite S. mansoni. No significant differences were seen in histopathology of the liver of any of the sheep but the pathological changes were more severe in the large and small intestines of sheep vaccinated with the heterologous parasite. In the second experiment with irradiated cercariae only one or two immunising exposures were used. The degree of protection in the adult worm load (9-11%) was not significant and no significant differences were noticed in the pathology of the vaccinated and control animals. In the third experiment four doses of irradiated organisms were used to vaccinate five groups of sheep: 3Kr or 6Kr cercariae were administered by percutaneous infection; 6Kr skin-transformed schistosomula were administered by intra muscular injection; the same 6Kr skin-transformed schistosomula were given by intravenous injection and 6Kr syringe transformed schistosomula were administered by intramuscular injection. The degree of protection (determined as the reduction in worm burden) achieved by these different procedures was respectively 72%, 61%, 77%, 56% and 78%. These results indicate the possibility of making a live vaccine against ovine schistosomiasis and show that effective immunisation is not dependent on the presence of a mature worm infection or on cercarial penetration of the skin by the immunising infection.", "contents": "Immunisation of sheep against Schistosoma mattheei using either irradiated cercariae or irradiated schistosomula. Irradiated cercariae, irradiated schistosomula, or heterologous infections were used to vaccinate sheep against Schistosoma mattheei infection. In the first experiment four doses of 10(4) S. mattheei cercariae irradiated at 6Kr were administered to sheep by percutaneous infection at 4 week intervals. This induced a 74% reduction in a challenge infection compared to control sheep while only 13% protection was achieved in a third group of sheep immunised with normal cercariae of the heterologous parasite S. mansoni. No significant differences were seen in histopathology of the liver of any of the sheep but the pathological changes were more severe in the large and small intestines of sheep vaccinated with the heterologous parasite. In the second experiment with irradiated cercariae only one or two immunising exposures were used. The degree of protection in the adult worm load (9-11%) was not significant and no significant differences were noticed in the pathology of the vaccinated and control animals. In the third experiment four doses of irradiated organisms were used to vaccinate five groups of sheep: 3Kr or 6Kr cercariae were administered by percutaneous infection; 6Kr skin-transformed schistosomula were administered by intra muscular injection; the same 6Kr skin-transformed schistosomula were given by intravenous injection and 6Kr syringe transformed schistosomula were administered by intramuscular injection. The degree of protection (determined as the reduction in worm burden) achieved by these different procedures was respectively 72%, 61%, 77%, 56% and 78%. These results indicate the possibility of making a live vaccine against ovine schistosomiasis and show that effective immunisation is not dependent on the presence of a mature worm infection or on cercarial penetration of the skin by the immunising infection."} {"id": "PMID:1262687", "title": "Comparative histochemical observations on the lipids in the immature and mature stages of Cotylophoron cotylophorum Paramphistomatidae: Digenea.", "content": "Immature and mature stages of the sheep amphistome Cotylophoron cotylophorum have been analysed histochemically for their lipids. Excretory ducts of the immature worms were the common sites for the accumulation of neutral lipids (triglycerides) and phospholipids which showed very sparse distribution at the corresponding sites in the adult. Phospholipids and lipoproteins observed in the tegument of the adult could not be seen in the immature form. Intestinal caecae of both forms showed the presence of diffused and granular lipids which were relatively less in the immature. The possible physiological significance of these differences in the lipid contents of the immature and mature forms has been discussed.", "contents": "Comparative histochemical observations on the lipids in the immature and mature stages of Cotylophoron cotylophorum Paramphistomatidae: Digenea. Immature and mature stages of the sheep amphistome Cotylophoron cotylophorum have been analysed histochemically for their lipids. Excretory ducts of the immature worms were the common sites for the accumulation of neutral lipids (triglycerides) and phospholipids which showed very sparse distribution at the corresponding sites in the adult. Phospholipids and lipoproteins observed in the tegument of the adult could not be seen in the immature form. Intestinal caecae of both forms showed the presence of diffused and granular lipids which were relatively less in the immature. The possible physiological significance of these differences in the lipid contents of the immature and mature forms has been discussed."} {"id": "PMID:1262688", "title": "Comparison of the Bell technique, a modified Kato thick smear technique, and a digestion method for the field diagnosis of schistosomiasis mansoni.", "content": "A modification of the Kato thick smear technique, the Bell filtration technique, and a digestion method were investigated to determine the relative merits of each for the detection of schistosome eggs in human faecal samples. The modified Kato technique was the method of choice because it was sensitive, simple to perform, and suitable for field use. The Bell filtration technique was equally sensitive in detecting light infections, but was more tedious and more complicated to perform than the thick smear technique.", "contents": "Comparison of the Bell technique, a modified Kato thick smear technique, and a digestion method for the field diagnosis of schistosomiasis mansoni. A modification of the Kato thick smear technique, the Bell filtration technique, and a digestion method were investigated to determine the relative merits of each for the detection of schistosome eggs in human faecal samples. The modified Kato technique was the method of choice because it was sensitive, simple to perform, and suitable for field use. The Bell filtration technique was equally sensitive in detecting light infections, but was more tedious and more complicated to perform than the thick smear technique."} {"id": "PMID:1262689", "title": "Studies with Brugia pahangi 12. The activity of levamisole.", "content": "The effects of levamisole on adults, third stage infective larvae, and microfilariae of Brugia pahangi were studied in in vitro culture and in vivo against developing stages in the vector mosquito and in infected cats. In vitro the drug was effective only at dose levels much higher than can be tolerated by mammals. It was active against the developmental stages of the worm in the vector Aedes aegypti. The drug was strongly microfilaricidal in cats but less effective against adult worms.", "contents": "Studies with Brugia pahangi 12. The activity of levamisole. The effects of levamisole on adults, third stage infective larvae, and microfilariae of Brugia pahangi were studied in in vitro culture and in vivo against developing stages in the vector mosquito and in infected cats. In vitro the drug was effective only at dose levels much higher than can be tolerated by mammals. It was active against the developmental stages of the worm in the vector Aedes aegypti. The drug was strongly microfilaricidal in cats but less effective against adult worms."} {"id": "PMID:1262691", "title": "Echinobothrium harfordi sp. nov. (Cestoda: Diphyllidae) from Raja naevus in the North Sea and English Channel.", "content": "Echinobothrium harfordi sp. nov. from the spiral intestine of Raja naevus in British waters is described and illustrated. The species most closely resembles E. affine as both possess two groups of eleven large apical hooks, but can be distinguished by fewer peduncle spines and by characteristics of the eggs. The intensity of infection in individual hosts was generally low, and although the incidence of infection was high in rays less than 35 cm in length, this fell towards zero in larger rays. The cestode showed a marked affinity for the first two tiers of the spiral intestine.", "contents": "Echinobothrium harfordi sp. nov. (Cestoda: Diphyllidae) from Raja naevus in the North Sea and English Channel. Echinobothrium harfordi sp. nov. from the spiral intestine of Raja naevus in British waters is described and illustrated. The species most closely resembles E. affine as both possess two groups of eleven large apical hooks, but can be distinguished by fewer peduncle spines and by characteristics of the eggs. The intensity of infection in individual hosts was generally low, and although the incidence of infection was high in rays less than 35 cm in length, this fell towards zero in larger rays. The cestode showed a marked affinity for the first two tiers of the spiral intestine."} {"id": "PMID:1262692", "title": "A comparative study of the death of schistosomula of Schistosoma haematobium and Schistosoma mansoni in the skin of mice and hamsters.", "content": "This study shows that some cercariae of S. haematobium and S. mansoni die during penetration of mouse or hamster skin. Approximately 30-38% of cercariae of both species die in mouse skin and 14-16% die in hamster skin. The greater number of cercariae which die in the skin of mice seems to account for the higher yield of adult worms recovered in hamsters. Adult worm recoveries from animals infected with S. haematobium were, however, only about half the worm recoveries from hosts infected with S. mansoni.", "contents": "A comparative study of the death of schistosomula of Schistosoma haematobium and Schistosoma mansoni in the skin of mice and hamsters. This study shows that some cercariae of S. haematobium and S. mansoni die during penetration of mouse or hamster skin. Approximately 30-38% of cercariae of both species die in mouse skin and 14-16% die in hamster skin. The greater number of cercariae which die in the skin of mice seems to account for the higher yield of adult worms recovered in hamsters. Adult worm recoveries from animals infected with S. haematobium were, however, only about half the worm recoveries from hosts infected with S. mansoni."} {"id": "PMID:1262693", "title": "Intermediate host antigens associated with the cercariae of Schistosoma haematobium.", "content": "Bulinus (Physopsis) africanus antigens were shown to be associated with the cercarial glycocalyx of Schistosoma haematobium using immunofluorescence and the Cercarienh\u00fcllen Reaktion. It is proposed that this snail antigen may sensitise the definitive host and that resistance to further invasion by cercariae could be induced in this manner.", "contents": "Intermediate host antigens associated with the cercariae of Schistosoma haematobium. Bulinus (Physopsis) africanus antigens were shown to be associated with the cercarial glycocalyx of Schistosoma haematobium using immunofluorescence and the Cercarienh\u00fcllen Reaktion. It is proposed that this snail antigen may sensitise the definitive host and that resistance to further invasion by cercariae could be induced in this manner."} {"id": "PMID:1262694", "title": "The anthelmintic effects of a new compound \"E\" (Friedheim) on Onchocerca gutturosa in the cow--a possible tertiary screening system for drug action against O. volvulus in man.", "content": "Three cows were treated with different levels of compound \"E\" which is known to have strong filaricidal activity. In all three animals the number of microfilariae of Onchocerca gutturosa declined after treatment. At autopsy most of the adult worms found were dead and in those still living embryogenesis appeared to have ceased. It is concluded that, despite the disadvantages, this system represents a possible way of assessing onchocercicidal activity before undertaking human trials.", "contents": "The anthelmintic effects of a new compound \"E\" (Friedheim) on Onchocerca gutturosa in the cow--a possible tertiary screening system for drug action against O. volvulus in man. Three cows were treated with different levels of compound \"E\" which is known to have strong filaricidal activity. In all three animals the number of microfilariae of Onchocerca gutturosa declined after treatment. At autopsy most of the adult worms found were dead and in those still living embryogenesis appeared to have ceased. It is concluded that, despite the disadvantages, this system represents a possible way of assessing onchocercicidal activity before undertaking human trials."} {"id": "PMID:1262695", "title": "The detection of antibodies in human and animal filariases by counterimmunoelectrophoresis with Dirofilaria immitis antigens.", "content": "Counterimmunoelectrophoresis revealed the presence of precipitin antibody in all of 6 dogs and the 1 cat infected with Dirofilaria immitis and in the serum of 17 of 24 individuals living in a setting of hyperendemic subperiodic bancroftian filariasis. Antigens used in the test were prepared from microfilariae and adult male D. immitis. Some humans and animals had antibodies to both antigens while others had antibodies against microfilariae or adult worms only. The presence of soluble circulating antigen was detected in the sera of two dogs with high microfilaraemias.", "contents": "The detection of antibodies in human and animal filariases by counterimmunoelectrophoresis with Dirofilaria immitis antigens. Counterimmunoelectrophoresis revealed the presence of precipitin antibody in all of 6 dogs and the 1 cat infected with Dirofilaria immitis and in the serum of 17 of 24 individuals living in a setting of hyperendemic subperiodic bancroftian filariasis. Antigens used in the test were prepared from microfilariae and adult male D. immitis. Some humans and animals had antibodies to both antigens while others had antibodies against microfilariae or adult worms only. The presence of soluble circulating antigen was detected in the sera of two dogs with high microfilaraemias."} {"id": "PMID:1262701", "title": "Ultrastructural cytochemistry of p-N,N-dimethylamino-beta-phenethylamine (DAPA) oxidation reactions.", "content": "The ultracytochemical localization of amine oxidase (AO) activity is demonstrated with a new substrate, p-N,N-dimethylamino-beta-phenethylamine (DAPA). DAPA was designed to yield a stronger reducing agent on oxidation by monoamine oxidase (MAO) than is obtained from the MAO substrate, tryptamine, upon oxidation. Thus MAO and possibly other oxidase(s) can be demonstrated with DAPA and the tetrazolium salt, 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl) tetrazolium chloride (BSPT). The latter is a nonosmiophilic tetrazolium salt which is reduced to an osmiophilic formazan. In addition, DAPA itself demonstrates AO activity ultracytochemically with and without BSPT. We speculate that either oxidative polymerization of DAPA or Schiff's base formation with protein after aldehyde formation is responsible for the latter reaction, which is made permanent for ultracytochemical localization by osmication at a later step. DAPA oxidation reaction products are demonstrated in guinea pig kidney, specifically in the endoplasmic reticulum, nuclear envelope and mitochondrial outer compartments and cristae. Differences in reaction product characteristics and localization in relation to formaldehyde fixation and the localization of reaction product in mitochondrial cristae, as well as outer compartments, suggest that DAPA oxidation is mediated through one or more MAOs and possible other oxidases.", "contents": "Ultrastructural cytochemistry of p-N,N-dimethylamino-beta-phenethylamine (DAPA) oxidation reactions. The ultracytochemical localization of amine oxidase (AO) activity is demonstrated with a new substrate, p-N,N-dimethylamino-beta-phenethylamine (DAPA). DAPA was designed to yield a stronger reducing agent on oxidation by monoamine oxidase (MAO) than is obtained from the MAO substrate, tryptamine, upon oxidation. Thus MAO and possibly other oxidase(s) can be demonstrated with DAPA and the tetrazolium salt, 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl) tetrazolium chloride (BSPT). The latter is a nonosmiophilic tetrazolium salt which is reduced to an osmiophilic formazan. In addition, DAPA itself demonstrates AO activity ultracytochemically with and without BSPT. We speculate that either oxidative polymerization of DAPA or Schiff's base formation with protein after aldehyde formation is responsible for the latter reaction, which is made permanent for ultracytochemical localization by osmication at a later step. DAPA oxidation reaction products are demonstrated in guinea pig kidney, specifically in the endoplasmic reticulum, nuclear envelope and mitochondrial outer compartments and cristae. Differences in reaction product characteristics and localization in relation to formaldehyde fixation and the localization of reaction product in mitochondrial cristae, as well as outer compartments, suggest that DAPA oxidation is mediated through one or more MAOs and possible other oxidases."} {"id": "PMID:1262696", "title": "Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse.", "content": "Osteopetrosis (op/op) is a new mutation in the mouse that is transmitted as an autosomal recessive linked with variant waddler (Va) on chromosome 12. Compared with normal littermates, young op/op mice have excessive accumulations of bone without marrow cavities, increases in bone matrix formation and concentrations of parafollicular cells of the thyroid, and are hypophosphatemic. Osteoclasts from op/op mice are small, few in number and have an abnormal cytoplasmic distribution of the lysosomal enzyme acid phosphatase. In contrast to the three other mutations that transmit osteopetrosis in mice, the skeletal signs of the disease slowly disappear in op/op animals after bone matrix formation declines about 6 weeks after birth from 145 percent to 20 percent of that in normal siblings. The main skeletal defect in op/op mice appears to be a severe restriction in bone remodeling that is capable of slowly removing the excessive skeletal mass characteristic of the disease only after bone formation has declined to one-fifth that of normal littermates.", "contents": "Osteopetrosis, a new recessive skeletal mutation on chromosome 12 of the mouse. Osteopetrosis (op/op) is a new mutation in the mouse that is transmitted as an autosomal recessive linked with variant waddler (Va) on chromosome 12. Compared with normal littermates, young op/op mice have excessive accumulations of bone without marrow cavities, increases in bone matrix formation and concentrations of parafollicular cells of the thyroid, and are hypophosphatemic. Osteoclasts from op/op mice are small, few in number and have an abnormal cytoplasmic distribution of the lysosomal enzyme acid phosphatase. In contrast to the three other mutations that transmit osteopetrosis in mice, the skeletal signs of the disease slowly disappear in op/op animals after bone matrix formation declines about 6 weeks after birth from 145 percent to 20 percent of that in normal siblings. The main skeletal defect in op/op mice appears to be a severe restriction in bone remodeling that is capable of slowly removing the excessive skeletal mass characteristic of the disease only after bone formation has declined to one-fifth that of normal littermates."} {"id": "PMID:1262697", "title": "The masked rat. An X-ray induced mutant with chronic blepharitis, alopecia, and pasteurellosis.", "content": "An autosomal recessive mutation had been previously X-ray-induced in the rat and named the masked rat (genotype mk/mk). This study describes the mutant's appearance, histology, and microflora. The rat's eyelids were swollen, often to the point of closure, and its face was partially covered by a brownish crust, giving the mutant a mask-like appearance. The chronic blepharitis was also accompanied by alopecia that appeared as bare patches across the mutant's back. Pasteurella pneumotropica was found in eyelids and on skin from all masked rats. The normal rat demonstrated a resistance to Pasteurella pneumotropica infection, or, conversely, the masked rat appeared to be genetically predisposed to pasteurellosis.", "contents": "The masked rat. An X-ray induced mutant with chronic blepharitis, alopecia, and pasteurellosis. An autosomal recessive mutation had been previously X-ray-induced in the rat and named the masked rat (genotype mk/mk). This study describes the mutant's appearance, histology, and microflora. The rat's eyelids were swollen, often to the point of closure, and its face was partially covered by a brownish crust, giving the mutant a mask-like appearance. The chronic blepharitis was also accompanied by alopecia that appeared as bare patches across the mutant's back. Pasteurella pneumotropica was found in eyelids and on skin from all masked rats. The normal rat demonstrated a resistance to Pasteurella pneumotropica infection, or, conversely, the masked rat appeared to be genetically predisposed to pasteurellosis."} {"id": "PMID:1262698", "title": "Esterases in the house fly. Polymorphisms and inheritance patterns.", "content": "Polyacrylamide gel electrophoresis was used to examine the variability and inheritance of esterases in five strains of the house fly, Musca domestica L. Individual zymograms exhibited 8 to 15 bands that could be assigned to one of five zones designated as A through E from anode to cathode. Correlations of P1-F1 banding patterns indicated the existence of at least 3 different loci in zone A. 2 each in zones B and C, and 4 in zone D; no clear inheritance patterns were discernable for the bands of zone E. Only the Es-5 locus of zone C was monomorphic in all of the strains studied. Eight loci possessed null alleles and codominant alleles were detected at six loci. The results suggest that esterases should prove useful for measuring relationships among fly populations or for various studies of population dynamics.", "contents": "Esterases in the house fly. Polymorphisms and inheritance patterns. Polyacrylamide gel electrophoresis was used to examine the variability and inheritance of esterases in five strains of the house fly, Musca domestica L. Individual zymograms exhibited 8 to 15 bands that could be assigned to one of five zones designated as A through E from anode to cathode. Correlations of P1-F1 banding patterns indicated the existence of at least 3 different loci in zone A. 2 each in zones B and C, and 4 in zone D; no clear inheritance patterns were discernable for the bands of zone E. Only the Es-5 locus of zone C was monomorphic in all of the strains studied. Eight loci possessed null alleles and codominant alleles were detected at six loci. The results suggest that esterases should prove useful for measuring relationships among fly populations or for various studies of population dynamics."} {"id": "PMID:1262699", "title": "Use of blood typing to confirm principles of coat-color genetics in horses.", "content": "The chestnut rule in equine coat-color genetics asserts that the inter se mating of chestnut horses never produces bay, black, brown or gray offspring. The gray rule asserts that a gray offspring must have at least one gray parent. Nine alleged exceptions to the chestnut rule, all involving bay offspring, and eight alleged exceptions to the gray rule, including four offspring that were also exceptions to the chestnut rule, were examined for parent-offspring genetic incompatibilities in as many as 17 genetic systems of blood-group markers. In all except one of the 17 cases it was possible to show that parentage had been incorrectly assigned. In 9 of the 16 exclusions it was possible to exclude the stallion irrespective of the mare and in one of the 16 exclusions it was possible to exclude the mare irrespective of the stallion. The percentage of exclusions, i.e., 94, was closely in line with expectation based on the established efficacy of these tests, about 90 percent, in excluding the incorrect stallion or stallions in paternity cases. Although the results strongly uphold the validity of the chestnut and gray rules in equine coat-color inheritance, they do not completely exclude the possibility that there could be rare exceptions to one or the other or both color rules. Insofar as equine registries may be concerned, the results clearly indicate that no alleged exception to the color rules should be considered eligible for registry in the absence of these tests.", "contents": "Use of blood typing to confirm principles of coat-color genetics in horses. The chestnut rule in equine coat-color genetics asserts that the inter se mating of chestnut horses never produces bay, black, brown or gray offspring. The gray rule asserts that a gray offspring must have at least one gray parent. Nine alleged exceptions to the chestnut rule, all involving bay offspring, and eight alleged exceptions to the gray rule, including four offspring that were also exceptions to the chestnut rule, were examined for parent-offspring genetic incompatibilities in as many as 17 genetic systems of blood-group markers. In all except one of the 17 cases it was possible to show that parentage had been incorrectly assigned. In 9 of the 16 exclusions it was possible to exclude the stallion irrespective of the mare and in one of the 16 exclusions it was possible to exclude the mare irrespective of the stallion. The percentage of exclusions, i.e., 94, was closely in line with expectation based on the established efficacy of these tests, about 90 percent, in excluding the incorrect stallion or stallions in paternity cases. Although the results strongly uphold the validity of the chestnut and gray rules in equine coat-color inheritance, they do not completely exclude the possibility that there could be rare exceptions to one or the other or both color rules. Insofar as equine registries may be concerned, the results clearly indicate that no alleged exception to the color rules should be considered eligible for registry in the absence of these tests."} {"id": "PMID:1262700", "title": "Abnormal feathers of the micromelic syndrome in White pekin ducks.", "content": "In an effort to provide further information concerning the pleiotropic effects of the gene mutation responsible for micromelia in White Pekin ducklings, a histological examination was made oq the abnormal feathers associated with the mutation. Abnormalities found in mutant feathers included decreased overall size, absence of prelumulae and prefiloplumulae feathers, an abnoramlly small rhachis with a disproportionally small medulla, thickening of the feather-sheath, and increased abundance of pulp cells. Embryos having the most abnormally developed feathers and the thickest periderm and feather-sheaths. The nature of many of the abnormalities found in mutant feathers suggests a common source in defective embryonic mesoderm.", "contents": "Abnormal feathers of the micromelic syndrome in White pekin ducks. In an effort to provide further information concerning the pleiotropic effects of the gene mutation responsible for micromelia in White Pekin ducklings, a histological examination was made oq the abnormal feathers associated with the mutation. Abnormalities found in mutant feathers included decreased overall size, absence of prelumulae and prefiloplumulae feathers, an abnoramlly small rhachis with a disproportionally small medulla, thickening of the feather-sheath, and increased abundance of pulp cells. Embryos having the most abnormally developed feathers and the thickest periderm and feather-sheaths. The nature of many of the abnormalities found in mutant feathers suggests a common source in defective embryonic mesoderm."} {"id": "PMID:1262708", "title": "Reactions to rubella vaccine and persistence of antibody in virgin-soil populations after vaccination and wild-virus-induced immunization.", "content": "Vaccination of two virgin-soil (without historical or serological evidence of past infection) populations of Amazon Indians with RA 27/3 rubella vaccine was followed by fever of greater than 100 F in 10% of the vacinees and by ephermeral arthralgia in 2%. These frequencies are not greater than those that have been reported for cosmopolitan populations of comparable ages. There was little or no secondary spread of the virus. Titers of hemagglutination-inhibiting antibody to rubella virus were prevalent in a third population of Amazon Indians, who had naturally acquired immunity and were unexposed to reinfection, and did not decline during a period of four to 12 years after infection. Antibody titers in the two virgin-soil populations immunized with RA 27/3 vaccine declined by twofold between four months and two and one-half years after vaccination but, at the end of that period, were not appreciably lower than antibody titers at four years in the naturally infected population. All age groups except children under one year of age responded to vaccination equally well.", "contents": "Reactions to rubella vaccine and persistence of antibody in virgin-soil populations after vaccination and wild-virus-induced immunization. Vaccination of two virgin-soil (without historical or serological evidence of past infection) populations of Amazon Indians with RA 27/3 rubella vaccine was followed by fever of greater than 100 F in 10% of the vacinees and by ephermeral arthralgia in 2%. These frequencies are not greater than those that have been reported for cosmopolitan populations of comparable ages. There was little or no secondary spread of the virus. Titers of hemagglutination-inhibiting antibody to rubella virus were prevalent in a third population of Amazon Indians, who had naturally acquired immunity and were unexposed to reinfection, and did not decline during a period of four to 12 years after infection. Antibody titers in the two virgin-soil populations immunized with RA 27/3 vaccine declined by twofold between four months and two and one-half years after vaccination but, at the end of that period, were not appreciably lower than antibody titers at four years in the naturally infected population. All age groups except children under one year of age responded to vaccination equally well."} {"id": "PMID:1262709", "title": "Attenuated, streptomycin-dependent Salmonella typhi oral vaccine: potential deleterious effects of lyophilization.", "content": "Four studies were done with streptomycin-dependent Salmonella typhi as an oral, attenuated vaccine. Studies 1 and 3 employed freshly harvested vaccine, whereas studies 2 and 4 involved lyophilized vaccine. Five to eight doses (3 x 10(10)-10(11) organisms/dose) were given; oral streptomycin (1.0 g) was administered concomitantly in studies 2 and 3, with only two of the doses of vaccine in study 1, and was not given in study 4. No adverse reactions were encountered in 179 vaccinated men, and 94% of the men excreted the vaccine. In challenge studies (which included the control groups) with 10(5) virulent S. typhi organisms (Quailes strain), the fresh vaccine was highly protective (66%-78% efficacy), while lyophilized vaccine gave no clinical protection. Fresh vaccine also interfered significantly with intestinal proliferation of virulent S. typhi; only 17% of the vaccinees excreted organisms as compared with 75% of the controls. Studies of protection in mice showed no difference between immunogen content of the fresh and the lyophilized vaccines. Field trials with streptomycin-dependent, oral typhoid vaccine must await development of a lyophilized product that will retain the protective properties of the vaccine.", "contents": "Attenuated, streptomycin-dependent Salmonella typhi oral vaccine: potential deleterious effects of lyophilization. Four studies were done with streptomycin-dependent Salmonella typhi as an oral, attenuated vaccine. Studies 1 and 3 employed freshly harvested vaccine, whereas studies 2 and 4 involved lyophilized vaccine. Five to eight doses (3 x 10(10)-10(11) organisms/dose) were given; oral streptomycin (1.0 g) was administered concomitantly in studies 2 and 3, with only two of the doses of vaccine in study 1, and was not given in study 4. No adverse reactions were encountered in 179 vaccinated men, and 94% of the men excreted the vaccine. In challenge studies (which included the control groups) with 10(5) virulent S. typhi organisms (Quailes strain), the fresh vaccine was highly protective (66%-78% efficacy), while lyophilized vaccine gave no clinical protection. Fresh vaccine also interfered significantly with intestinal proliferation of virulent S. typhi; only 17% of the vaccinees excreted organisms as compared with 75% of the controls. Studies of protection in mice showed no difference between immunogen content of the fresh and the lyophilized vaccines. Field trials with streptomycin-dependent, oral typhoid vaccine must await development of a lyophilized product that will retain the protective properties of the vaccine."} {"id": "PMID:1262710", "title": "False-positive rabbit ileal loop reactions attributed to Vibrio parahaemolyticus broth filtrates.", "content": "Vibrio parahaemolyticus broth filtrates have previously been shown to produce positive reactions in rabbit ileal loops only if concentrated 10-fold by lyophilization. This method of concentration produces solutions that contain greater than 20% NaCl. In the present study, however, concentrations of NaCl of greater than or equal to 4% induced positive responses in ileal loops, and desalting rendered previously reactive, concentrated broth filtrates negative. Therefore, enterotoxin was not demonstrated in our broth filtrates of V. parahaemolyticus, a finding which suggests that previous studies require further evaluation. Since most culture media contain 0.5% NaCl, it is important to determine and to control the NaCl content and the osmolality of all lyophilized concentrates tested in the ligated rabbit ileum.", "contents": "False-positive rabbit ileal loop reactions attributed to Vibrio parahaemolyticus broth filtrates. Vibrio parahaemolyticus broth filtrates have previously been shown to produce positive reactions in rabbit ileal loops only if concentrated 10-fold by lyophilization. This method of concentration produces solutions that contain greater than 20% NaCl. In the present study, however, concentrations of NaCl of greater than or equal to 4% induced positive responses in ileal loops, and desalting rendered previously reactive, concentrated broth filtrates negative. Therefore, enterotoxin was not demonstrated in our broth filtrates of V. parahaemolyticus, a finding which suggests that previous studies require further evaluation. Since most culture media contain 0.5% NaCl, it is important to determine and to control the NaCl content and the osmolality of all lyophilized concentrates tested in the ligated rabbit ileum."} {"id": "PMID:1262711", "title": "Role of the immune response in age-dependent resistance of mice to encephalitis due to Sindbis virus.", "content": "One- to eight-week-old mice were studied after subcutaneous inoculation of Sindbis virus. Local replication at the site of inoculation, transient viremia, and invasion of the brain were found in mice of all ages, although the quantities of virus were greater in younger mice. Death occurred in 100% of one-week-old mice, 28% of two-week-old mice, and none of the mice four weeks old or older. Pathologic examination of the brains on day 7 after infection revealed a mononuclear inflammatory infiltrate in all mice, with evidence of necrosis in the youngest. Neutralizing antibody was present by day 3 and reached high titers by day 6 in all age groups. Specific stimulation of cells from the draining lymph node by Sindbis virus antigen was also demonstrable by day 6 in all groups. There was no evidence for a primary role of humoral or cellular immune responses in the age-dependent resistance of mice to infection with Sindbis virus.", "contents": "Role of the immune response in age-dependent resistance of mice to encephalitis due to Sindbis virus. One- to eight-week-old mice were studied after subcutaneous inoculation of Sindbis virus. Local replication at the site of inoculation, transient viremia, and invasion of the brain were found in mice of all ages, although the quantities of virus were greater in younger mice. Death occurred in 100% of one-week-old mice, 28% of two-week-old mice, and none of the mice four weeks old or older. Pathologic examination of the brains on day 7 after infection revealed a mononuclear inflammatory infiltrate in all mice, with evidence of necrosis in the youngest. Neutralizing antibody was present by day 3 and reached high titers by day 6 in all age groups. Specific stimulation of cells from the draining lymph node by Sindbis virus antigen was also demonstrable by day 6 in all groups. There was no evidence for a primary role of humoral or cellular immune responses in the age-dependent resistance of mice to infection with Sindbis virus."} {"id": "PMID:1262715", "title": "Yersinia pestis infection in Vietnam. II. Quantiative blood cultures and detection of endotoxin in the cerebrospinal fluid of patients with meningitis.", "content": "Quantitative blood cultures were obtained from 42 patients with acute Yersinia pestis infection to determine whether the concentration of bacteria in blood influenced the clinical severity and outcome of illness. In 17 bacteremic patients, colony counts in blood cultures ranged from less than 10 to 4 X 10(7)/ml. Three of five patients with colony counts of greater than 10(2)/ml died, and two patients survived episodes of hypotension. Results from plasma limulus tests were positive at the time of admission in three of 10 patients tested, and these three patients had bacteremia with colony counts of greater than 10(2)/ml. Meningitis developed in three patients and pneumonia in two patients; these five patients a-l had buboes in the axillary region. Endotoxin was detected with the limulus test in the cerebrospinal fluid in the three patients with meningitis. Ten patients randomly assigned to receive streptomycin or trimethoprim-sulfamethoxazole survived. Those treated with streptomycin had a shorter median duration of fever and a lower incidence of complications than did the patients treated with trimethoprim-sulfamethoxazole.", "contents": "Yersinia pestis infection in Vietnam. II. Quantiative blood cultures and detection of endotoxin in the cerebrospinal fluid of patients with meningitis. Quantitative blood cultures were obtained from 42 patients with acute Yersinia pestis infection to determine whether the concentration of bacteria in blood influenced the clinical severity and outcome of illness. In 17 bacteremic patients, colony counts in blood cultures ranged from less than 10 to 4 X 10(7)/ml. Three of five patients with colony counts of greater than 10(2)/ml died, and two patients survived episodes of hypotension. Results from plasma limulus tests were positive at the time of admission in three of 10 patients tested, and these three patients had bacteremia with colony counts of greater than 10(2)/ml. Meningitis developed in three patients and pneumonia in two patients; these five patients a-l had buboes in the axillary region. Endotoxin was detected with the limulus test in the cerebrospinal fluid in the three patients with meningitis. Ten patients randomly assigned to receive streptomycin or trimethoprim-sulfamethoxazole survived. Those treated with streptomycin had a shorter median duration of fever and a lower incidence of complications than did the patients treated with trimethoprim-sulfamethoxazole."} {"id": "PMID:1262716", "title": "An enzymatic assay for chloramphenicol with partially purified chloramphenicol acetyltransferase.", "content": "In an enzymatic assay for chloramphenicol, chloramphenicol acetyltransferase partially purified by affinity chromatography was used; [3H]acetyl coenzyme A served as a substrate. The purified enzyme was sensitive to p-hydroxymercuribenzoate but insensitive to 5,5'-dithio-bis-2-nitrobenzoic acid. The Michaelis-Menten constant was 10.5 muM. The operating range of the enzymatic assay was 0-30 mug/ml. The coefficient of variation was 1.9% at a concentration of 10 mug/ml. The method correlated well with a microbiological agar-paper disk method for mock unknown sera (r = 0.997) and serum or urine specimens (r = 0.993). The enzymatic assay was unaffected by the presence of any of 12 other antibiotics in tested serum.", "contents": "An enzymatic assay for chloramphenicol with partially purified chloramphenicol acetyltransferase. In an enzymatic assay for chloramphenicol, chloramphenicol acetyltransferase partially purified by affinity chromatography was used; [3H]acetyl coenzyme A served as a substrate. The purified enzyme was sensitive to p-hydroxymercuribenzoate but insensitive to 5,5'-dithio-bis-2-nitrobenzoic acid. The Michaelis-Menten constant was 10.5 muM. The operating range of the enzymatic assay was 0-30 mug/ml. The coefficient of variation was 1.9% at a concentration of 10 mug/ml. The method correlated well with a microbiological agar-paper disk method for mock unknown sera (r = 0.997) and serum or urine specimens (r = 0.993). The enzymatic assay was unaffected by the presence of any of 12 other antibiotics in tested serum."} {"id": "PMID:1262769", "title": "Reassessment of Q waves in left bundle branch block.", "content": "This study disputes a number of recent reports claiming that abnormal Q waves or a QS configuration in inferior leads (II, III and AVF) coexisting with left bundle branch block is highly suggestive of, and indeed specific for, myocardial infarction. Five patients reported herein demonstrate disappearance of Q waves in inferior leads on spontaneous reversal of LBBB to normal conduction. This necessitates the conclusion that these Q waves represent a postdivisional conduction variant most closely equivalent to left anterior fascicular block coexisting with predivisional LBBB. Absence of inferior R waves in the five patients demonstrating LBBB is explicable by as little as a 20 msec conduction delay in the posterior fascicle coexisting with a higher grade conduction defect in the anterior fascicle. It is concluded that LBBB with a QS configuration in II, III and AVF cannot be considered diagnostic of inferior wall infarction since it regularly results from impaired conduction of the left anterior and possibly the left posterior fascicle (to a lesser extent), which may be reversible.", "contents": "Reassessment of Q waves in left bundle branch block. This study disputes a number of recent reports claiming that abnormal Q waves or a QS configuration in inferior leads (II, III and AVF) coexisting with left bundle branch block is highly suggestive of, and indeed specific for, myocardial infarction. Five patients reported herein demonstrate disappearance of Q waves in inferior leads on spontaneous reversal of LBBB to normal conduction. This necessitates the conclusion that these Q waves represent a postdivisional conduction variant most closely equivalent to left anterior fascicular block coexisting with predivisional LBBB. Absence of inferior R waves in the five patients demonstrating LBBB is explicable by as little as a 20 msec conduction delay in the posterior fascicle coexisting with a higher grade conduction defect in the anterior fascicle. It is concluded that LBBB with a QS configuration in II, III and AVF cannot be considered diagnostic of inferior wall infarction since it regularly results from impaired conduction of the left anterior and possibly the left posterior fascicle (to a lesser extent), which may be reversible."} {"id": "PMID:1262770", "title": "Computer characterization of sinus rhythm.", "content": "Sinus rhythm tracings, including sinus tachycardia and bradycardia, are characterized quantitatively by means of an ECG measurement program which has been subjected to rigorous evaluation. The analysis is performed on tracings of short duration (10 sec). The features of regularity and stability are considered for the R wavetrain. Regularity is evaluated from the normalized differences between sucessive RR intervals. Stability is determined by the ratio of maximum and minimum RR interval durations. Due to the difficulities of automatic beat-to-beat detection and measurement of P waves, an estimate of the PR interval is obtained from a pseudo-PR interval determined from certain features of the P and R wavetrains. The constancy of this pseudo-PR interval is evaluated, and its absolute value is uded as a characteristic of the type of sinus rhythm.", "contents": "Computer characterization of sinus rhythm. Sinus rhythm tracings, including sinus tachycardia and bradycardia, are characterized quantitatively by means of an ECG measurement program which has been subjected to rigorous evaluation. The analysis is performed on tracings of short duration (10 sec). The features of regularity and stability are considered for the R wavetrain. Regularity is evaluated from the normalized differences between sucessive RR intervals. Stability is determined by the ratio of maximum and minimum RR interval durations. Due to the difficulities of automatic beat-to-beat detection and measurement of P waves, an estimate of the PR interval is obtained from a pseudo-PR interval determined from certain features of the P and R wavetrains. The constancy of this pseudo-PR interval is evaluated, and its absolute value is uded as a characteristic of the type of sinus rhythm."} {"id": "PMID:1262771", "title": "Angular velocity of the QRS loop of the vectrocardiogram in the normal heart.", "content": "Angular velocity expressed in radians/sec of the rotation movement of the QRS loop at intervals of 2.5 msecs was calculated from a computer program written in Fortran IV. Frontal, horizontal and left sagittal planes were recorded in 125 normal subjects for analysis. The range of angular velocity for 375 QRS loops was from a few radians/sec to a maximum of 95 radians/sec. Average values of maximum angular velocities were: frontal plane, 46.2 radians/sec, horizontal plane, 41 radians/sec, and left sagittal plane, 34.1 radians/sec. Angular velocity expressed as a periodic function of the vector loop is characterized by polyphasic curves. In the frontal plane, curves tend to be more symmetrical with maximum values in the middle. Angular velocity curves are an alternate expression of analysis of planar vector loops employed in clinical practice. Their normal ranges are given in this paper.", "contents": "Angular velocity of the QRS loop of the vectrocardiogram in the normal heart. Angular velocity expressed in radians/sec of the rotation movement of the QRS loop at intervals of 2.5 msecs was calculated from a computer program written in Fortran IV. Frontal, horizontal and left sagittal planes were recorded in 125 normal subjects for analysis. The range of angular velocity for 375 QRS loops was from a few radians/sec to a maximum of 95 radians/sec. Average values of maximum angular velocities were: frontal plane, 46.2 radians/sec, horizontal plane, 41 radians/sec, and left sagittal plane, 34.1 radians/sec. Angular velocity expressed as a periodic function of the vector loop is characterized by polyphasic curves. In the frontal plane, curves tend to be more symmetrical with maximum values in the middle. Angular velocity curves are an alternate expression of analysis of planar vector loops employed in clinical practice. Their normal ranges are given in this paper."} {"id": "PMID:1262772", "title": "Left ventricular parietal block: diagnostic and clinical study.", "content": "Fifty-five patients with widened QRS complexes due to the presence of slurred S waves or of terminal slurrings on R waves, in more than three leads, with no infarction or bundle branch and fascicular blocks, were studied with the usual clinical examinations as well as vectorcardiographic recording. A parietal block of the left ventricle was diagnosed when, in the presence of a normal development of ventricular depolarization in the initial and middle phases, the terminal QRS loop was delayed, sometimes irregular and displaced leftward and posteriorly. When this delay was directed to the right, the ventricular localization was puzzling. The comparison of the electrocardiographic (ECG) and vectorcardiographic (VCG) data on the terminal part of ventricular depolarization showed some discrepancies and revealed the greater importance of VCG investigation for the study and the localization of parietal blocks. The pathogenesis of such minor conduction disturbances is not yet clear, since the experimental data on the anatomical-functional structures are different: the Purkinje network, Purkinje fiber-muscle junction or common myocardium. In some cases we think it is possible to localize the structure concerned; in any case we can always localize it at the level of the free ventricular wall.", "contents": "Left ventricular parietal block: diagnostic and clinical study. Fifty-five patients with widened QRS complexes due to the presence of slurred S waves or of terminal slurrings on R waves, in more than three leads, with no infarction or bundle branch and fascicular blocks, were studied with the usual clinical examinations as well as vectorcardiographic recording. A parietal block of the left ventricle was diagnosed when, in the presence of a normal development of ventricular depolarization in the initial and middle phases, the terminal QRS loop was delayed, sometimes irregular and displaced leftward and posteriorly. When this delay was directed to the right, the ventricular localization was puzzling. The comparison of the electrocardiographic (ECG) and vectorcardiographic (VCG) data on the terminal part of ventricular depolarization showed some discrepancies and revealed the greater importance of VCG investigation for the study and the localization of parietal blocks. The pathogenesis of such minor conduction disturbances is not yet clear, since the experimental data on the anatomical-functional structures are different: the Purkinje network, Purkinje fiber-muscle junction or common myocardium. In some cases we think it is possible to localize the structure concerned; in any case we can always localize it at the level of the free ventricular wall."} {"id": "PMID:1262773", "title": "T-wave changes secondary to left anterior hemiblock as shown by study of intermittent and alternating patterns.", "content": "T-wave changes in spontaneous intermittent and alternating LAH have been described. Attention has been called to the fact that, with the onset of LAH conduction, the T-wave axis shifts oppositely to that of the QRS, thus widening the QRS-T angle in the frontal plane by about 95 degrees. This has the effect of causing T-waves to become upright in leads II, III and AVF, even in those in whom T-waves were previously inverted. This described dicordance of QRS and T-wave axes is considered as evidence that LAH conduction is in fact a true conduction abnormality. As a corollary, an inverted T-wave in leads II, III or AVF in the presence of LAH is a primary abnormality and may be an indication of inferior wall myocardial ischemia or infarction. T-waves are lowered but not inverted in lead I as a result of LAH conduction and precordial leads are variably but not significantly altered.", "contents": "T-wave changes secondary to left anterior hemiblock as shown by study of intermittent and alternating patterns. T-wave changes in spontaneous intermittent and alternating LAH have been described. Attention has been called to the fact that, with the onset of LAH conduction, the T-wave axis shifts oppositely to that of the QRS, thus widening the QRS-T angle in the frontal plane by about 95 degrees. This has the effect of causing T-waves to become upright in leads II, III and AVF, even in those in whom T-waves were previously inverted. This described dicordance of QRS and T-wave axes is considered as evidence that LAH conduction is in fact a true conduction abnormality. As a corollary, an inverted T-wave in leads II, III or AVF in the presence of LAH is a primary abnormality and may be an indication of inferior wall myocardial ischemia or infarction. T-waves are lowered but not inverted in lead I as a result of LAH conduction and precordial leads are variably but not significantly altered."} {"id": "PMID:1262774", "title": "An easily applied and removed dry annular suction electrode.", "content": "A new type of self-retaining dry metal electrode for the electrocardiogram (ECG) is described which adheres to the skin by the application of negative pressure to an annulus surrounding the electrode, which is a bare silver. Data are presented for the factors which govern the adherence to the skin and the range of initial impedance and the values obtained at 2, 5, 10 and 20 minutes and with tap water under the electrodes. The initial impedance is usually high (0.18 to 10 megohms) and decreases progressively with time. Tap water placed under the electrodes dramatically reduces the initial range of impedance. Such electrodes, when used with an amplifier with an adequately high input impedance, can be used for recording electrocardiograms in a variety of situations.", "contents": "An easily applied and removed dry annular suction electrode. A new type of self-retaining dry metal electrode for the electrocardiogram (ECG) is described which adheres to the skin by the application of negative pressure to an annulus surrounding the electrode, which is a bare silver. Data are presented for the factors which govern the adherence to the skin and the range of initial impedance and the values obtained at 2, 5, 10 and 20 minutes and with tap water under the electrodes. The initial impedance is usually high (0.18 to 10 megohms) and decreases progressively with time. Tap water placed under the electrodes dramatically reduces the initial range of impedance. Such electrodes, when used with an amplifier with an adequately high input impedance, can be used for recording electrocardiograms in a variety of situations."} {"id": "PMID:1262775", "title": "Sinoventricular conduction in atrial standstill.", "content": "Sinoventricular rhythm implies preserved sinus node function with conduction of impulses to the A-V junction without generalized atrial excitation. Impulse propagation in such cases is presumably via specialized internodal tracts. In this present case, synchronized but localized activation from an area of the right atrium preceded each QRS, without generalized atrial depolarization. These recordings are offered as further evidence for the clinical occurrence of sinoventricular rhythm in humans.", "contents": "Sinoventricular conduction in atrial standstill. Sinoventricular rhythm implies preserved sinus node function with conduction of impulses to the A-V junction without generalized atrial excitation. Impulse propagation in such cases is presumably via specialized internodal tracts. In this present case, synchronized but localized activation from an area of the right atrium preceded each QRS, without generalized atrial depolarization. These recordings are offered as further evidence for the clinical occurrence of sinoventricular rhythm in humans."} {"id": "PMID:1262776", "title": "Effects of the pacing site in sinus node reentrant tachycardia.", "content": "His bundle recordings and premature atrial stimulation from coronary sinus, mid-right atrium and high-right atrium were performed in a patient with repetitive supraventricular tachycardias. Regardless of the paced site, there was a range of coupling intervals during which testing stimuli elicited short runs of premature beats. The corresponding P waves were positive in leads I, II and III and had a high-to-low right atrial activation sequence. Their morphology was similar to that of sinus beats. However, sustained tachycardia occurred only when pacing was performed from the coronary sinus. Therefore, it is postulated that the site of stimulation might be important in the genesis and (perhaps) perpetuation of this arrhythmia by changing the site and (or) mode of entry into the area where this type of tachycardia occurs. Though sinus node reentry was the most likely mechanism, it could not be determined whether the circuit involved the sinus node per se or the so called perinodal fibers.", "contents": "Effects of the pacing site in sinus node reentrant tachycardia. His bundle recordings and premature atrial stimulation from coronary sinus, mid-right atrium and high-right atrium were performed in a patient with repetitive supraventricular tachycardias. Regardless of the paced site, there was a range of coupling intervals during which testing stimuli elicited short runs of premature beats. The corresponding P waves were positive in leads I, II and III and had a high-to-low right atrial activation sequence. Their morphology was similar to that of sinus beats. However, sustained tachycardia occurred only when pacing was performed from the coronary sinus. Therefore, it is postulated that the site of stimulation might be important in the genesis and (perhaps) perpetuation of this arrhythmia by changing the site and (or) mode of entry into the area where this type of tachycardia occurs. Though sinus node reentry was the most likely mechanism, it could not be determined whether the circuit involved the sinus node per se or the so called perinodal fibers."} {"id": "PMID:1262777", "title": "The R-on-T phenomenon during supraventricular tachycardia in childhood.", "content": "The electrocardiographic R-on-T phenomenon was observed in the absence of Wolff-Parkinson-White syndrome during recurrent episodes of supraventricular tachycardia (SVT) with rates between 240 to 275 per minute in a 5 year old boy. The rapid ventricular response during SVT corroborates the recent finding of a short refractory period of the A-V node in children. The demonstration of the R-on-T phenomenon in this child may be important in attempting to understand the pathogenesis of sudden death in children.", "contents": "The R-on-T phenomenon during supraventricular tachycardia in childhood. The electrocardiographic R-on-T phenomenon was observed in the absence of Wolff-Parkinson-White syndrome during recurrent episodes of supraventricular tachycardia (SVT) with rates between 240 to 275 per minute in a 5 year old boy. The rapid ventricular response during SVT corroborates the recent finding of a short refractory period of the A-V node in children. The demonstration of the R-on-T phenomenon in this child may be important in attempting to understand the pathogenesis of sudden death in children."} {"id": "PMID:1262778", "title": "Spontaneous atrial premature depolarizations during paroxysmal reentrant tachycardia.", "content": "The spontaneous onset and termination of many episodes of paroxysmal tachycardia, each initiated by an atrial premature depolarization, were studied in one patient. Surface electrocardiograms alone were inadequate to define the mechanisms underlying the frequent irregularity of atrial and ventricular cycle lengths during the tachycardia and the nature of spontaneous termination of the tachycardia. Unipolar atrial electrograms demonstrated that the irregularity during the tachycardia was due to premature atrial depolarizations that reset the reentrant cycle sustaining the tachycardia, and each spontaneous termination was due to an even more premature atrial depolarization interrupting the reentrant pathway. The genesis of the atrial premature depolarizations resetting and terminating the tachycardia, and their relationship to those initiating the tachycardia, are discussed.", "contents": "Spontaneous atrial premature depolarizations during paroxysmal reentrant tachycardia. The spontaneous onset and termination of many episodes of paroxysmal tachycardia, each initiated by an atrial premature depolarization, were studied in one patient. Surface electrocardiograms alone were inadequate to define the mechanisms underlying the frequent irregularity of atrial and ventricular cycle lengths during the tachycardia and the nature of spontaneous termination of the tachycardia. Unipolar atrial electrograms demonstrated that the irregularity during the tachycardia was due to premature atrial depolarizations that reset the reentrant cycle sustaining the tachycardia, and each spontaneous termination was due to an even more premature atrial depolarization interrupting the reentrant pathway. The genesis of the atrial premature depolarizations resetting and terminating the tachycardia, and their relationship to those initiating the tachycardia, are discussed."} {"id": "PMID:1262780", "title": "Temporary unipolar pacing using a dual cathode.", "content": "Using standard biopolar, temporary pacing catheters, thresholds were measured in four configurations: (1) bipolar (distal electrode negative, proximal electrode positive); (2) distal unipolar (distal electrode negative, right arm electrode positive); (3) proximal unipolar (proximal electrode negative, right arm electrode positive); (4) dual-cathode unipolar (distal and proximal electrodes negative, right arm electrode positive). With one exception, the bipolar threshold was the lower of the distal or proximal unipolar thresholds, suggesting that bipolar temporary pacing is reliable because one of the two electrodes is in good contact with the endocardium. In both the distal and proximal unipolar configurations there were numerous instances of high threshold and failure to pace. However, with one exception, in all cases either the distal or proximal unipolar threshold was normal and thus pacing was possible and effective in the dual-cathode configuration. Dual-cathode unipolar pacing combines the excitation and sensing advantages of unipolar pacing with the reliability of bipolar stimulation.", "contents": "Temporary unipolar pacing using a dual cathode. Using standard biopolar, temporary pacing catheters, thresholds were measured in four configurations: (1) bipolar (distal electrode negative, proximal electrode positive); (2) distal unipolar (distal electrode negative, right arm electrode positive); (3) proximal unipolar (proximal electrode negative, right arm electrode positive); (4) dual-cathode unipolar (distal and proximal electrodes negative, right arm electrode positive). With one exception, the bipolar threshold was the lower of the distal or proximal unipolar thresholds, suggesting that bipolar temporary pacing is reliable because one of the two electrodes is in good contact with the endocardium. In both the distal and proximal unipolar configurations there were numerous instances of high threshold and failure to pace. However, with one exception, in all cases either the distal or proximal unipolar threshold was normal and thus pacing was possible and effective in the dual-cathode configuration. Dual-cathode unipolar pacing combines the excitation and sensing advantages of unipolar pacing with the reliability of bipolar stimulation."} {"id": "PMID:1262782", "title": "Colchicine stimulation of pyrogen production by human blood leukocytes.", "content": "The effect of colchicine, an anti-inflammatory agent, on endogenous pyrogen (EP) production by human blood leukocytes in vitro was examined. Colchicine not only failed to suppress EP production by human leukocytes stimulated by phagocytosis, but, in the absence of other stimuli, micromolar concentrations of the drug induced pyrogen production and release by both polymorphonuclear (PMN) and mononuclear leukocytes. The response was dose related, occurring at concentrations above 0.1 muM. Colcemid and vinblastine, other agents which bind to microtubular protein, also induced pyrogen release from human leukocytes, whereas lumicolchicine, a light-alerted derivative of colchicine without affinity for microtubules, was ineffective. Colchicine did not induce EP production by rabbit leukocytes, even at 100 muM concentration. Studies of the mechanism of PMN leukocyte activation by Colcemid indicated that although the time required for contact between drug and leukocyte was brief, pyrogen production and release did not begin for 6 or more hours. If added during this time, puromycin prevented subsequent production and release of pyrogen. These results indicated that agents which interfere with the assembly of microtubules induce EP production and secretion by human leukocytes in vitro.", "contents": "Colchicine stimulation of pyrogen production by human blood leukocytes. The effect of colchicine, an anti-inflammatory agent, on endogenous pyrogen (EP) production by human blood leukocytes in vitro was examined. Colchicine not only failed to suppress EP production by human leukocytes stimulated by phagocytosis, but, in the absence of other stimuli, micromolar concentrations of the drug induced pyrogen production and release by both polymorphonuclear (PMN) and mononuclear leukocytes. The response was dose related, occurring at concentrations above 0.1 muM. Colcemid and vinblastine, other agents which bind to microtubular protein, also induced pyrogen release from human leukocytes, whereas lumicolchicine, a light-alerted derivative of colchicine without affinity for microtubules, was ineffective. Colchicine did not induce EP production by rabbit leukocytes, even at 100 muM concentration. Studies of the mechanism of PMN leukocyte activation by Colcemid indicated that although the time required for contact between drug and leukocyte was brief, pyrogen production and release did not begin for 6 or more hours. If added during this time, puromycin prevented subsequent production and release of pyrogen. These results indicated that agents which interfere with the assembly of microtubules induce EP production and secretion by human leukocytes in vitro."} {"id": "PMID:1262783", "title": "Mutant lines of guinea pig L2C leukemia. I. Deletion of Ia alloantigens is associated with a loss in immunogenicity of tumor-associated transplantation antigens.", "content": "Five different lines of a strain 2 guinea pig leukemia (L2C) which had been carried in different laboratories share certain chromosomal markers and have a common surface immunoglobulin idiotypic determinant indicating that they have a common origin. All these leukemic lines have on their surface of the B alloantigen (equivalent of the murine H-2K and H-2D antigens) and four of these five lines have on their surface the Ia alloantigens normally present on the strain 2 lymphocytes. The result of a study of the growth and rejection patterns of these leukemias in inbred and random-bred guinea pigs of selected histocompatibility type indicates that both the B and Ia antigens can act as transplantation antigens in guinea pigs. Immunization protection tests in syngeneic animals demonstrated that the four Ia-positive leukemias possessed a tumor-associated transplantation antigen (TATA), while the one Ia-positive leukemias possessed a tumor-associated transplantation antigen (TATA), while the one Ia-negative leukemia by this criteria did not appear to have TATA. However, crisscross immunization protection tests demonstrated that preimmunization of syngeneic animals with an Ia-positive L2C line lead to a subsequent protection against challenge with the Ia-negative leukemia. Immunization with the Ia-negative line never protected against a subsequent challenge with any of the leukemic cells of L2C lines. These results strongly suggest that the Ia-negative leukemia possessed a TATA that can be recognized but is not itself immunogenic, and also indicate that Ia antigens on L2C cells are functionally associated with TATA and can act as immunological carries for tumor transplantation determinants.", "contents": "Mutant lines of guinea pig L2C leukemia. I. Deletion of Ia alloantigens is associated with a loss in immunogenicity of tumor-associated transplantation antigens. Five different lines of a strain 2 guinea pig leukemia (L2C) which had been carried in different laboratories share certain chromosomal markers and have a common surface immunoglobulin idiotypic determinant indicating that they have a common origin. All these leukemic lines have on their surface of the B alloantigen (equivalent of the murine H-2K and H-2D antigens) and four of these five lines have on their surface the Ia alloantigens normally present on the strain 2 lymphocytes. The result of a study of the growth and rejection patterns of these leukemias in inbred and random-bred guinea pigs of selected histocompatibility type indicates that both the B and Ia antigens can act as transplantation antigens in guinea pigs. Immunization protection tests in syngeneic animals demonstrated that the four Ia-positive leukemias possessed a tumor-associated transplantation antigen (TATA), while the one Ia-positive leukemias possessed a tumor-associated transplantation antigen (TATA), while the one Ia-negative leukemia by this criteria did not appear to have TATA. However, crisscross immunization protection tests demonstrated that preimmunization of syngeneic animals with an Ia-positive L2C line lead to a subsequent protection against challenge with the Ia-negative leukemia. Immunization with the Ia-negative line never protected against a subsequent challenge with any of the leukemic cells of L2C lines. These results strongly suggest that the Ia-negative leukemia possessed a TATA that can be recognized but is not itself immunogenic, and also indicate that Ia antigens on L2C cells are functionally associated with TATA and can act as immunological carries for tumor transplantation determinants."} {"id": "PMID:1262784", "title": "The membrane attack mechanism of complement: the three polypeptide chain structure of the eigth component (C8).", "content": "The purification of human C8 in milligram quantities from outdated human serum was achieved by ammonium sulfate precipitation (37.5-50% saturation) and ion exchange column chromatography employing CM-32 cellulose and QAE-Sephadex. The yield of C8 activity ranged from 2-9%, and the average purification was 1,700-fold. Fully reduced C8 was shown by SDS polyacrylamide gel electrophoresis to have three polypeptide chains which were present in equimolor ratios: alpha, 77,000 daltons; beta, 63,000 daltons; and gamma, 13,700 daltons. C8 denaturation by SDS and urea in the absence of reducing agents revealed two noncovalently linked subunits: alpha-gamma, 99,000 daltons, and beta, 75,000 daltons.", "contents": "The membrane attack mechanism of complement: the three polypeptide chain structure of the eigth component (C8). The purification of human C8 in milligram quantities from outdated human serum was achieved by ammonium sulfate precipitation (37.5-50% saturation) and ion exchange column chromatography employing CM-32 cellulose and QAE-Sephadex. The yield of C8 activity ranged from 2-9%, and the average purification was 1,700-fold. Fully reduced C8 was shown by SDS polyacrylamide gel electrophoresis to have three polypeptide chains which were present in equimolor ratios: alpha, 77,000 daltons; beta, 63,000 daltons; and gamma, 13,700 daltons. C8 denaturation by SDS and urea in the absence of reducing agents revealed two noncovalently linked subunits: alpha-gamma, 99,000 daltons, and beta, 75,000 daltons."} {"id": "PMID:1262785", "title": "The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils.", "content": "24 di-, tri-, and tetrapeptides have been synthesized as a start of a systematic study of the structural requirements for chemotactic activity and lysosomal enzyme-releasing ability in rabbit neutrophils. All but two of them are N-formyl methionyl peptides. Using the method of Zigmond and Hirsch (10), two representative peptides, F-Met-Leu-Phe and F-Met-Met-Met, were shown to stimulate directed, as well as, random locomotion; thus, they were truly chemotactic. The various peptides showed a wide spread in activity. F-Met-Leu-Phe, the most active peptide studied, had an ED50 for induced migration of 7 X 10(-11) M and for lysozyme and beta-glucuronidase release of 2.4 X 10(-10) M and 2.6 X 10(-10) M, respectively; the least active, Met-Leu-Glu was 26 million times less active in these respects. The relation of activity to structure is exceedingly specific, very small changes in structure making large changes in activity. Moreover, this specificity exhibits a definite regularity and pattern; the activity of a given peptide depends not only on its constituent amino acids but on the position of the amino acid in the peptide chain. Most striking in this last regards is the high activity conferred by phenylalanine when it is in the carboxyl terminal position of a tripeptide, whereas, as the second amino acid from the NH2 terminal end whether in a tripeptide or a dipeptide, it contributes no more to the activity than other amino acids with hydrophobic side chains such as leucine or methionine. The high activity and the specificity and nature of the structural requirements strongly suggest that the primary interaction of peptide and neutrophil leading to either chemotaxis or lysosomal enzyme release is a binding of the peptide with a stereospecific receptor on the neutrophil surface. Whether all chemotactic factors act through the same receptor is not known. An essentially exact correlation exists between the concentrations of the various synthetic peptides required to induce migration and their ability to induce release of lysozyme or beta-glucuronidase. This implies that these two neutrophil functions are triggered by teh same primary interaction; possibly, the binding of the peptides to the same putative receptor. A higher concentration of a given peptide is required to stimulate lysosomal enzyme release than a corresponding migratory response. A slightly but significantly higher concentration of peptide is required to induce beta-glucuronidase secretion than lysozyme release.", "contents": "The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. 24 di-, tri-, and tetrapeptides have been synthesized as a start of a systematic study of the structural requirements for chemotactic activity and lysosomal enzyme-releasing ability in rabbit neutrophils. All but two of them are N-formyl methionyl peptides. Using the method of Zigmond and Hirsch (10), two representative peptides, F-Met-Leu-Phe and F-Met-Met-Met, were shown to stimulate directed, as well as, random locomotion; thus, they were truly chemotactic. The various peptides showed a wide spread in activity. F-Met-Leu-Phe, the most active peptide studied, had an ED50 for induced migration of 7 X 10(-11) M and for lysozyme and beta-glucuronidase release of 2.4 X 10(-10) M and 2.6 X 10(-10) M, respectively; the least active, Met-Leu-Glu was 26 million times less active in these respects. The relation of activity to structure is exceedingly specific, very small changes in structure making large changes in activity. Moreover, this specificity exhibits a definite regularity and pattern; the activity of a given peptide depends not only on its constituent amino acids but on the position of the amino acid in the peptide chain. Most striking in this last regards is the high activity conferred by phenylalanine when it is in the carboxyl terminal position of a tripeptide, whereas, as the second amino acid from the NH2 terminal end whether in a tripeptide or a dipeptide, it contributes no more to the activity than other amino acids with hydrophobic side chains such as leucine or methionine. The high activity and the specificity and nature of the structural requirements strongly suggest that the primary interaction of peptide and neutrophil leading to either chemotaxis or lysosomal enzyme release is a binding of the peptide with a stereospecific receptor on the neutrophil surface. Whether all chemotactic factors act through the same receptor is not known. An essentially exact correlation exists between the concentrations of the various synthetic peptides required to induce migration and their ability to induce release of lysozyme or beta-glucuronidase. This implies that these two neutrophil functions are triggered by teh same primary interaction; possibly, the binding of the peptides to the same putative receptor. A higher concentration of a given peptide is required to stimulate lysosomal enzyme release than a corresponding migratory response. A slightly but significantly higher concentration of peptide is required to induce beta-glucuronidase secretion than lysozyme release."} {"id": "PMID:1262786", "title": "Characterization of DNA excreted from phytohemagglutinin-stimulated lymphocytes.", "content": "The DNA released into the culture medium after phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes has been purified and characterized. It is double stranded, sediments at 7-8S in alkaline sucrose, and has a Tm determined optically and by thermal elution from hydroxyapatite that is substantially lower than that found for lymphocyte cell DNA. Media DNA contains a major component reassociating with an average Cot-1/2 of 87 mol X s/liter, compared to a Cot-1/2 of 770 mol X s/liter for the unique fraction of cell DNA as measured by reassociation in 0.6 M Na+. This component of media DNA consists of unique sequence elements which are largely shared in media DNA preparations from cultures derived from different cell donors. The marked difference between media DNA and cell DNA indicates that media DNA is not derived from cell death and lysis, rather than some unique portion of lymphocyte DNA is apparently excreted from the cells during PHA-stimulated growth.", "contents": "Characterization of DNA excreted from phytohemagglutinin-stimulated lymphocytes. The DNA released into the culture medium after phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes has been purified and characterized. It is double stranded, sediments at 7-8S in alkaline sucrose, and has a Tm determined optically and by thermal elution from hydroxyapatite that is substantially lower than that found for lymphocyte cell DNA. Media DNA contains a major component reassociating with an average Cot-1/2 of 87 mol X s/liter, compared to a Cot-1/2 of 770 mol X s/liter for the unique fraction of cell DNA as measured by reassociation in 0.6 M Na+. This component of media DNA consists of unique sequence elements which are largely shared in media DNA preparations from cultures derived from different cell donors. The marked difference between media DNA and cell DNA indicates that media DNA is not derived from cell death and lysis, rather than some unique portion of lymphocyte DNA is apparently excreted from the cells during PHA-stimulated growth."} {"id": "PMID:1262787", "title": "Inhibition of maturation of human precursor lymphocytes by coformycin, an inhibitor of the enzyme adenosine deaminase.", "content": "High concentrations of adenosine are known to be toxic to fibroblasts and lymphocytes under conditions of in vitro culture (1,2). Normally, accumulation of adenosine nucleotides in all mammalian cells is prevented by the presence of adenosine deaminase, an aminohydrolase which converts adenosine to inosine (3). A genetically determined deficiency of adenosine deaminase has been associated with the autosomal recessive form of severe combined immunodeficiency, a syndrome in which precursor lymphocytes fail to mature into T cells and B cells (4-7). Erythrocytes of affected infants convert exogenous adenosine to AMP and ATP at an abnormally increased rate as a consequence of the enzyme defect, and ATP at an abnormally increased rate as a consequence of the enzyme defect, and fail to form inosine from the exogenous adenosine (8). These metabolic disturbances can be mimicked in normal erythrocytes by coformycin (8), a potent competitive inhibitor of adenosine deaminase (9, 10). In this study, the effects of coformycin were examined on the in vitro function of normal lymphocytes.", "contents": "Inhibition of maturation of human precursor lymphocytes by coformycin, an inhibitor of the enzyme adenosine deaminase. High concentrations of adenosine are known to be toxic to fibroblasts and lymphocytes under conditions of in vitro culture (1,2). Normally, accumulation of adenosine nucleotides in all mammalian cells is prevented by the presence of adenosine deaminase, an aminohydrolase which converts adenosine to inosine (3). A genetically determined deficiency of adenosine deaminase has been associated with the autosomal recessive form of severe combined immunodeficiency, a syndrome in which precursor lymphocytes fail to mature into T cells and B cells (4-7). Erythrocytes of affected infants convert exogenous adenosine to AMP and ATP at an abnormally increased rate as a consequence of the enzyme defect, and ATP at an abnormally increased rate as a consequence of the enzyme defect, and fail to form inosine from the exogenous adenosine (8). These metabolic disturbances can be mimicked in normal erythrocytes by coformycin (8), a potent competitive inhibitor of adenosine deaminase (9, 10). In this study, the effects of coformycin were examined on the in vitro function of normal lymphocytes."} {"id": "PMID:1262788", "title": "The HLA system in the families of patients with juvenile diabetes mellitus.", "content": "The HLA and Bf genotypes were determined in 10 families with one or more children with JDM. A statistically significant association was found between HLA-D-identity and the chance to present JDM within a sibship. No such association was detectable with the SD antigens. A highly significant increase in the frequency of intra-HLA recombination was also found in these families.", "contents": "The HLA system in the families of patients with juvenile diabetes mellitus. The HLA and Bf genotypes were determined in 10 families with one or more children with JDM. A statistically significant association was found between HLA-D-identity and the chance to present JDM within a sibship. No such association was detectable with the SD antigens. A highly significant increase in the frequency of intra-HLA recombination was also found in these families."} {"id": "PMID:1262790", "title": "Spatial probability learning by alcoholic Korsakoff patients.", "content": "Performance of 10 alcoholic Korsakoff patients was compared to that of 10 normal and 10 alcoholic control subjects on each of three different schedules of spatial probability learning (50:50, 70:30, and 30:70) using monetary reinforcement and a correction procedure. There was some evidence that the Korsakoff patients were less sensitive than normals to the effects of reward: Although on all three schedules, choice ratios by normal subjects approximated the reinforcement ratios, the choice ratios of Korsakoffs on the second and third schedules remained close to the reinforcement ratio acquired with the first schedule. In addition, the Korsakoffs made an abnormal number of perseverative errors early in training. On most measures, performance by alcoholic controls fell between that of the other two groups.", "contents": "Spatial probability learning by alcoholic Korsakoff patients. Performance of 10 alcoholic Korsakoff patients was compared to that of 10 normal and 10 alcoholic control subjects on each of three different schedules of spatial probability learning (50:50, 70:30, and 30:70) using monetary reinforcement and a correction procedure. There was some evidence that the Korsakoff patients were less sensitive than normals to the effects of reward: Although on all three schedules, choice ratios by normal subjects approximated the reinforcement ratios, the choice ratios of Korsakoffs on the second and third schedules remained close to the reinforcement ratio acquired with the first schedule. In addition, the Korsakoffs made an abnormal number of perseverative errors early in training. On most measures, performance by alcoholic controls fell between that of the other two groups."} {"id": "PMID:1262791", "title": "The effects of divided attention on information processing in manual tracking.", "content": "Six subjects performed a manual tracking task concurrently uith each of two secondary tasks: in input task (auditory signal detection) and an output task (application of a constant force). A feedback-control analysis of tracking performance was utilized to analyze the time-sharing decrements observed in mean squared errer, in terms of components due to processing delay, addition of internal processing noise, and change in response bias (tracking gain). The results indicated that only the parameters measuring noise and gain were sensitive to time-sharing conditions, and these only to concurrent performance of the force application task. It is concluded that limits of attention in dual-task performance are more severe in output than in input stages of processing, but that these limits are not necessarily those of a single-channel bottleneck. Instead, a broader conception of attention is proposed: one that included changes in processing noise and shifts in response bias, as attention-related phenomena.", "contents": "The effects of divided attention on information processing in manual tracking. Six subjects performed a manual tracking task concurrently uith each of two secondary tasks: in input task (auditory signal detection) and an output task (application of a constant force). A feedback-control analysis of tracking performance was utilized to analyze the time-sharing decrements observed in mean squared errer, in terms of components due to processing delay, addition of internal processing noise, and change in response bias (tracking gain). The results indicated that only the parameters measuring noise and gain were sensitive to time-sharing conditions, and these only to concurrent performance of the force application task. It is concluded that limits of attention in dual-task performance are more severe in output than in input stages of processing, but that these limits are not necessarily those of a single-channel bottleneck. Instead, a broader conception of attention is proposed: one that included changes in processing noise and shifts in response bias, as attention-related phenomena."} {"id": "PMID:1262792", "title": "Color vision and hue categorization in young human infants.", "content": "Two studies examined the organization of color perception in 4-month-old human infants. In Study 1, infants looked at selected spectral stimuli repeatedly until their visual attention waned. The stimuli represented instances of basic adult hue categories - blue, green, yellow, and red. Following habituation, infants were shown a series of wavelengths which were the same as or different from the stimuli first seen. Analyses of infant attention during this dishabituation phase of the study indicated that infants categorize wavelengths by perceptual similarity; that is, they see hues in the spectrum much as adults do. In Study 2, a group of infants who looked at the alteration of two wavelengths from the same hue category habituated as did the group of infants who looked at the repitition of a single wavelength from that category, but a group of infants who looked at two wavelengths from different categories habituated at a slower rate. Data from the two studies suggest a high degree of organization of the color world prior to language acquisition.", "contents": "Color vision and hue categorization in young human infants. Two studies examined the organization of color perception in 4-month-old human infants. In Study 1, infants looked at selected spectral stimuli repeatedly until their visual attention waned. The stimuli represented instances of basic adult hue categories - blue, green, yellow, and red. Following habituation, infants were shown a series of wavelengths which were the same as or different from the stimuli first seen. Analyses of infant attention during this dishabituation phase of the study indicated that infants categorize wavelengths by perceptual similarity; that is, they see hues in the spectrum much as adults do. In Study 2, a group of infants who looked at the alteration of two wavelengths from the same hue category habituated as did the group of infants who looked at the repitition of a single wavelength from that category, but a group of infants who looked at two wavelengths from different categories habituated at a slower rate. Data from the two studies suggest a high degree of organization of the color world prior to language acquisition."} {"id": "PMID:1262793", "title": "Irrelevance of figural identity for resolving ambiguities in apparent motion.", "content": "In order to examine the degree to which form perception affects the formation of apparent-motion experience, subjects were presented with nine ambiguous apparent-motion situations, where the elements of each single flash were various figures. One of the interpretations of each situation preserved the figural identity of the figures across flashes. It was found that figural identity does not have any effect on determining the type of motion experienced, except when the figural analysis involved is relatively simple.", "contents": "Irrelevance of figural identity for resolving ambiguities in apparent motion. In order to examine the degree to which form perception affects the formation of apparent-motion experience, subjects were presented with nine ambiguous apparent-motion situations, where the elements of each single flash were various figures. One of the interpretations of each situation preserved the figural identity of the figures across flashes. It was found that figural identity does not have any effect on determining the type of motion experienced, except when the figural analysis involved is relatively simple."} {"id": "PMID:1262794", "title": "The role of pattern goodness in the reproduction of backward masked patterns.", "content": "Four experiments investigated the role of pattern goodness in backward masking using five- and four-dot patterns constructed by placing dots in the cells of a 3 x 3 matrix. In Experiment 1, subjects rated the goodness of these patterns and the results replicated previous work showing that good patterns had few alternatives. In Experiment 2, the dot patterns were the target stimuli in a backward masking task using a variety of masking stimuli. For all masking, good patterns were reproduced more accurately than poor patterns. In Experiment 3, the goodness of the masking stimulus was varied. The results indicated that good patterns were reproduced more accurately (replicating Experiment 2) and that good patterns were less effective as stimulus than were poor patterns. In Experiment 4, a long interstimulus interval which precluded masking was used to determine whether goodness affected encoding or memory. At these intervals, there were no differences among patterns, suggesting that the effect of pattern goodness was on rate of encoding. These results demonstrate the importance of configural properties in pattern perception.", "contents": "The role of pattern goodness in the reproduction of backward masked patterns. Four experiments investigated the role of pattern goodness in backward masking using five- and four-dot patterns constructed by placing dots in the cells of a 3 x 3 matrix. In Experiment 1, subjects rated the goodness of these patterns and the results replicated previous work showing that good patterns had few alternatives. In Experiment 2, the dot patterns were the target stimuli in a backward masking task using a variety of masking stimuli. For all masking, good patterns were reproduced more accurately than poor patterns. In Experiment 3, the goodness of the masking stimulus was varied. The results indicated that good patterns were reproduced more accurately (replicating Experiment 2) and that good patterns were less effective as stimulus than were poor patterns. In Experiment 4, a long interstimulus interval which precluded masking was used to determine whether goodness affected encoding or memory. At these intervals, there were no differences among patterns, suggesting that the effect of pattern goodness was on rate of encoding. These results demonstrate the importance of configural properties in pattern perception."} {"id": "PMID:1262795", "title": "Attending to forty-nine spatial positions at once.", "content": "Simultaneous attention to 49 spatial positions resulted in the processing of threshold information from one of those positions essentially identical to the processing when the subject knew in advance that that position would be tested. This result held true when the task consisted of detection of the presence of a briefly presented dot. The same result held true for 9 spatial positions when the task consisted of report of the briefly presented letter in the target position.", "contents": "Attending to forty-nine spatial positions at once. Simultaneous attention to 49 spatial positions resulted in the processing of threshold information from one of those positions essentially identical to the processing when the subject knew in advance that that position would be tested. This result held true when the task consisted of detection of the presence of a briefly presented dot. The same result held true for 9 spatial positions when the task consisted of report of the briefly presented letter in the target position."} {"id": "PMID:1262796", "title": "Separate \"what\" and \"where\" decision mechanisms in processing a dichotic tonal sequence.", "content": "Right-handed subjects were presented with a dichotic tonal sequence, whose basic pattern consisted of three 800-Hz tones followed by two 400-Hz tones on the channel and simultaneously three 400-Hz tones followed by two 800-Hz tones on the other. All tones were 250 msec in duration and separated by 250-msec pauses. On any given stimulus presentation, most subjects reported the sequence of pitches delivered to one ear and ignored the other. They further tended significantly to report the sequence delivered to the right ear rather than to the left. However, each tone appeared to be localized in the ear receiving the higher frequency, regardless of which ear was followed for pitch and regardless of whether the higher or lower frequency was in fact perceived.", "contents": "Separate \"what\" and \"where\" decision mechanisms in processing a dichotic tonal sequence. Right-handed subjects were presented with a dichotic tonal sequence, whose basic pattern consisted of three 800-Hz tones followed by two 400-Hz tones on the channel and simultaneously three 400-Hz tones followed by two 800-Hz tones on the other. All tones were 250 msec in duration and separated by 250-msec pauses. On any given stimulus presentation, most subjects reported the sequence of pitches delivered to one ear and ignored the other. They further tended significantly to report the sequence delivered to the right ear rather than to the left. However, each tone appeared to be localized in the ear receiving the higher frequency, regardless of which ear was followed for pitch and regardless of whether the higher or lower frequency was in fact perceived."} {"id": "PMID:1262797", "title": "Preliminary letter identification in the perception of words and nonwords.", "content": "Words with mixed uppercase and lowercase letters (e.g. fAdE) were perceived more accurately than mixed-case pseudowords (e.g. gAdE), and mixed-case pseudowords were perceived more accurately than mixed-case unrelated letter strings (e.g. eFdT). In addition, same-case words were perceived more accurately than their mixed-case counterparts. The same held true for pseudowords but not for unrelated letter strings. The results are compatible with the view that both letter identify and visual form information are used in word perception.", "contents": "Preliminary letter identification in the perception of words and nonwords. Words with mixed uppercase and lowercase letters (e.g. fAdE) were perceived more accurately than mixed-case pseudowords (e.g. gAdE), and mixed-case pseudowords were perceived more accurately than mixed-case unrelated letter strings (e.g. eFdT). In addition, same-case words were perceived more accurately than their mixed-case counterparts. The same held true for pseudowords but not for unrelated letter strings. The results are compatible with the view that both letter identify and visual form information are used in word perception."} {"id": "PMID:1262814", "title": "Locomotion of bluefish.", "content": "1. Pressure previously measured on the body surface of swimming bluefish were resolved into their backward vectorial components to allow calculation of profile drag. It was 0.18 kg at a speed of 1.8 m/sec. Tangential drag was calculated as if for a thin plate of an area equal to that of the fish. It was 0.08 kg at 1.8 m/sec. Net drag, 0.26 kg, was the sum of profile and tangential drag. 2. Thrust and drag also were calculated from the changes of acceleration measured during steady swimming, assuming that thrust took place only during the acceleration phase, whereas drag occurred during both acceleration and deceleration. This drag was 0.08 kg at a speed of 1.1 m/sec. It is compatible with the drag of 0.26 at 1.8 m/sec calculated from profile and tangential drag provided drag varies as the square of velocity. 3. The force required to produced maximal acceleration was measured during a scare. It was calculated to be 6.9 kg at a peak acceleration of 3 g. 4. The compression strength of th vertebrae was found to be approximately 20 kg per cm2, or roughly three times the force encountered during maximal acceleration. This safety factor of 3 would be reduced when the back was curved, or if opposing groups of muscles were under tension. 5. The finding that a bluefish can accelerate at 3 g and that the vertebral column is strongg enough to withstand this force indicates that the muscles and body structure of a bluefish would be able to withstand the force of gravity if the fish were otherwise equipped for terrestrial life. This fish may have evolved these strengths simultaneously with land animals. It is speculated that other fish may have evolved some degree of strength to overcome inertia and drag during aquatic locomotion, and this evolution may have been a prelude to terrestrial locomotion.", "contents": "Locomotion of bluefish. 1. Pressure previously measured on the body surface of swimming bluefish were resolved into their backward vectorial components to allow calculation of profile drag. It was 0.18 kg at a speed of 1.8 m/sec. Tangential drag was calculated as if for a thin plate of an area equal to that of the fish. It was 0.08 kg at 1.8 m/sec. Net drag, 0.26 kg, was the sum of profile and tangential drag. 2. Thrust and drag also were calculated from the changes of acceleration measured during steady swimming, assuming that thrust took place only during the acceleration phase, whereas drag occurred during both acceleration and deceleration. This drag was 0.08 kg at a speed of 1.1 m/sec. It is compatible with the drag of 0.26 at 1.8 m/sec calculated from profile and tangential drag provided drag varies as the square of velocity. 3. The force required to produced maximal acceleration was measured during a scare. It was calculated to be 6.9 kg at a peak acceleration of 3 g. 4. The compression strength of th vertebrae was found to be approximately 20 kg per cm2, or roughly three times the force encountered during maximal acceleration. This safety factor of 3 would be reduced when the back was curved, or if opposing groups of muscles were under tension. 5. The finding that a bluefish can accelerate at 3 g and that the vertebral column is strongg enough to withstand this force indicates that the muscles and body structure of a bluefish would be able to withstand the force of gravity if the fish were otherwise equipped for terrestrial life. This fish may have evolved these strengths simultaneously with land animals. It is speculated that other fish may have evolved some degree of strength to overcome inertia and drag during aquatic locomotion, and this evolution may have been a prelude to terrestrial locomotion."} {"id": "PMID:1262815", "title": "Induction of antler growth in a congenitally polled Scottish red deer stag.", "content": "A congenitally polled red deer stag was captured from a Scottish deer forest and kept in an enclosure for observations. The animal had rudimentary antler pedicles but no antlers, and during five years of study no significant antler development occurred. Amputation of the apex of one antler pedicle in May 1974 when the stat was 12 years of age resulted in the growth of a complete antler on the operated side, and this antler was subsequently cleaned and cast in the normal way and a new antler cycle was initiated. The result illustrates that the primary abnormality in this polled stag lay not in his inability to grow antler, but in his inability to develop fully formed antler pedicles from which normal antler tissue could differentiate. Traumatizing the rudimentary pedicle had the effect of stimulating growth of antler tissue, and once this was formed the process of cleaning, casting and regrowth occurred spontaneously. The incomplete development of the antler pedicles is considered to be responsible for the absence of antlers in the majority of \"hummels\" in Scotland, and the etiology of the condition is discussed.", "contents": "Induction of antler growth in a congenitally polled Scottish red deer stag. A congenitally polled red deer stag was captured from a Scottish deer forest and kept in an enclosure for observations. The animal had rudimentary antler pedicles but no antlers, and during five years of study no significant antler development occurred. Amputation of the apex of one antler pedicle in May 1974 when the stat was 12 years of age resulted in the growth of a complete antler on the operated side, and this antler was subsequently cleaned and cast in the normal way and a new antler cycle was initiated. The result illustrates that the primary abnormality in this polled stag lay not in his inability to grow antler, but in his inability to develop fully formed antler pedicles from which normal antler tissue could differentiate. Traumatizing the rudimentary pedicle had the effect of stimulating growth of antler tissue, and once this was formed the process of cleaning, casting and regrowth occurred spontaneously. The incomplete development of the antler pedicles is considered to be responsible for the absence of antlers in the majority of \"hummels\" in Scotland, and the etiology of the condition is discussed."} {"id": "PMID:1262816", "title": "Mitotic activity and nucleic acid precursor incorporation in denervated and innervated limb stumps of axolotl larvae.", "content": "Mitotic activity and DNA and RNA precursor incorporation were compared in innervated regenerating limbs and in denervated, non-regenerating limbs on days 8 and 9 post-amputation. Innervated limbs had well-developed cone stage blastemas which showed high cellular mitotic indices and H3-thymidine labeling indices of 0.40-0.50 and H3-uridine labeling indices of 0.50-0.75. In contrast, denervated limbs showed dedifferentiated cells distally under thickened wound epithelia, but essentially no mitotic activity and no blastema formation. These dedifferentiated cells showed lower levels of H3-thymidine (0.10 index) and H3-uridine (0.50) incorporation than regenerating limbs. Labeling indices of wound epithelia are also compared.", "contents": "Mitotic activity and nucleic acid precursor incorporation in denervated and innervated limb stumps of axolotl larvae. Mitotic activity and DNA and RNA precursor incorporation were compared in innervated regenerating limbs and in denervated, non-regenerating limbs on days 8 and 9 post-amputation. Innervated limbs had well-developed cone stage blastemas which showed high cellular mitotic indices and H3-thymidine labeling indices of 0.40-0.50 and H3-uridine labeling indices of 0.50-0.75. In contrast, denervated limbs showed dedifferentiated cells distally under thickened wound epithelia, but essentially no mitotic activity and no blastema formation. These dedifferentiated cells showed lower levels of H3-thymidine (0.10 index) and H3-uridine (0.50) incorporation than regenerating limbs. Labeling indices of wound epithelia are also compared."} {"id": "PMID:1262817", "title": "Furrowing in altered cell surfaces.", "content": "Understanding the process which established the cell division mechanism requires analysis of the role of the responding surface as well as that of stimulatory subsurface structures. Cell surface was altered by the expansion which occurs during exovate formation. Exovates appear on the surface of fertilized Arbacia lixula, Paracentrotus lividus and Echinarachnius parma eggs in response to extreme flattening. They result from cytoplasmic outflow initiated in a very restricted portion of the egg surface. Observations of the formation process in pigmented A. lixula eggs revealed that the original surface may be expanded about 100 fold as the exovate swells. When exovates formed 15-30 minutes after fertilization contain the mitotic apparatus, they divide synchronously with flattened controls. If nucleated exovates are established after the beginning of first cleavage, furrows appear in ten minutes. Exovates established after the beginning of second cleavage develop furrows four minutes after the entrance of the the mitsotic apparatus. Cytoplasm beneath damaged exovate surfaces sometimes develops partial constrictions independently of the surface in the plane the furrow would have occupied. These results suggest that normal surface structure is unnecessary for furrow establishment and function.", "contents": "Furrowing in altered cell surfaces. Understanding the process which established the cell division mechanism requires analysis of the role of the responding surface as well as that of stimulatory subsurface structures. Cell surface was altered by the expansion which occurs during exovate formation. Exovates appear on the surface of fertilized Arbacia lixula, Paracentrotus lividus and Echinarachnius parma eggs in response to extreme flattening. They result from cytoplasmic outflow initiated in a very restricted portion of the egg surface. Observations of the formation process in pigmented A. lixula eggs revealed that the original surface may be expanded about 100 fold as the exovate swells. When exovates formed 15-30 minutes after fertilization contain the mitotic apparatus, they divide synchronously with flattened controls. If nucleated exovates are established after the beginning of first cleavage, furrows appear in ten minutes. Exovates established after the beginning of second cleavage develop furrows four minutes after the entrance of the the mitsotic apparatus. Cytoplasm beneath damaged exovate surfaces sometimes develops partial constrictions independently of the surface in the plane the furrow would have occupied. These results suggest that normal surface structure is unnecessary for furrow establishment and function."} {"id": "PMID:1262818", "title": "Polarizing activity in the developing limb of the Syrian hamster.", "content": "The transplantation of small pieces of tissue from the limb buds of 9 1/2 -10 day hamster embryos to the wing bud of the chick results in the induction of supernumerary wing structures. The anteroposterior polarity of these induced structures is under the control of the transplanted hamster tissue. The developing hamster limb thus has limb polarizing activity similar to that found in avian species and, as in the chick, the activity is found primarily in the posterior region of the limb bud.", "contents": "Polarizing activity in the developing limb of the Syrian hamster. The transplantation of small pieces of tissue from the limb buds of 9 1/2 -10 day hamster embryos to the wing bud of the chick results in the induction of supernumerary wing structures. The anteroposterior polarity of these induced structures is under the control of the transplanted hamster tissue. The developing hamster limb thus has limb polarizing activity similar to that found in avian species and, as in the chick, the activity is found primarily in the posterior region of the limb bud."} {"id": "PMID:1262819", "title": "Optimal temperatures for inner-ear performance in gekkonoid lizards.", "content": "Temperature effects on the cochlear alternating potentials are described in lizards of the Eublepharidae (4 spp. and subspp.), Diplodactylinae (2 spp.), Gekkoninae (7 spp. and subspp.) and Sphaerodactylidae (1 sp.). Pure tones (50-15,000 Hz) were applied to the anaesthetized gecko's external ear. Sound intensity needed for a standard response was plotted (db versus frequency). A total of 249 such sensitivity functions were obtained from 50 animals, at temperatures of 15-40 degrees C. For each species, an optimal sensitivity function is definable by its extreme sensitivity and relative smoothness. This is obtained throughout a specific optimal temperature range. At lower temperatures, the function is less sensitive and its best sensitivity is at a lower frequency. The specific optimal cochlear temperature range resembles the specific ecological temperature preferendum where known. Both are broader in gekkonoid than in iguanid lizards. The temperature effects on the sensitivity function occur even with aerial or mechanical stimulation at the oval window after middle ear extirpation. Hence they arise in the inner ear. Their magnitude (db/ degrees C) is half that known from auditory nerve potentials. When accurate auditory data are desired, the specific optimal temperature and its possible seasonal variation require consideration. This increases the need for proper identification of subjects by name and origin, and for monitoring experimental thermal parameters, including pre-experimental acclimation.", "contents": "Optimal temperatures for inner-ear performance in gekkonoid lizards. Temperature effects on the cochlear alternating potentials are described in lizards of the Eublepharidae (4 spp. and subspp.), Diplodactylinae (2 spp.), Gekkoninae (7 spp. and subspp.) and Sphaerodactylidae (1 sp.). Pure tones (50-15,000 Hz) were applied to the anaesthetized gecko's external ear. Sound intensity needed for a standard response was plotted (db versus frequency). A total of 249 such sensitivity functions were obtained from 50 animals, at temperatures of 15-40 degrees C. For each species, an optimal sensitivity function is definable by its extreme sensitivity and relative smoothness. This is obtained throughout a specific optimal temperature range. At lower temperatures, the function is less sensitive and its best sensitivity is at a lower frequency. The specific optimal cochlear temperature range resembles the specific ecological temperature preferendum where known. Both are broader in gekkonoid than in iguanid lizards. The temperature effects on the sensitivity function occur even with aerial or mechanical stimulation at the oval window after middle ear extirpation. Hence they arise in the inner ear. Their magnitude (db/ degrees C) is half that known from auditory nerve potentials. When accurate auditory data are desired, the specific optimal temperature and its possible seasonal variation require consideration. This increases the need for proper identification of subjects by name and origin, and for monitoring experimental thermal parameters, including pre-experimental acclimation."} {"id": "PMID:1262820", "title": "Irradiation inhibits the regeneration of aneurogenic limbs.", "content": "The developing arms of axolotl larvae from the 2-digit stage onward and the aneurogenic arms of surgically denervated larvae maintained in parabiosis are able to regenerate after amputation. Such regeneration is uniformly inhibited by local irradiation of the arm, whether innervated or not. This demonstration refutes a recent hypothesis that X-rays interfere with a special activity of nerves required for regeneration, and supports the earlier concept that X-rays act directly on those cells which must proliferate to form the regenerated tissues.", "contents": "Irradiation inhibits the regeneration of aneurogenic limbs. The developing arms of axolotl larvae from the 2-digit stage onward and the aneurogenic arms of surgically denervated larvae maintained in parabiosis are able to regenerate after amputation. Such regeneration is uniformly inhibited by local irradiation of the arm, whether innervated or not. This demonstration refutes a recent hypothesis that X-rays interfere with a special activity of nerves required for regeneration, and supports the earlier concept that X-rays act directly on those cells which must proliferate to form the regenerated tissues."} {"id": "PMID:1262821", "title": "Morphology and kinetics of spermatogenesis in Xenopus laevis.", "content": "The light microscopic characteristics of spermatogenic stages of the germ cell line in the anuran, Xenopus laevis, have been described as they appear in both nuclear squash preparations and plastic embedded thick sections of intact testes. Tritiated thymidine autoradiography was employed to unequivocally identify stages. Using this methodology, it was determined that the premeiotic DNA synthetic period occurs in a cell which is morphologically indistinguishable from a late secondary spermatogonial cell. In addition, kinetic studies with tritiated thymidine were employed to determine the duration of meiotic prophase and spermiogenesis in Xenopus. Results indicate that at 18 degrees C, the most rapidly matururing cells in the testis spend four days in leptotene, six days in zygotene, twelve days in pachytene, one day in diplotene, one day in meiotic division, and twelve days in spermiogenesis. An estimate for the duration of the premeiotic S stage was indirectly calculated from combined data to yield a value of six to seven days. Pooled spermatocyte counts measuring the frequency of occurrence of individual stages produced results which correlated closely with estimates obtained by tritiated thymidine labelling. Individual counts, however, show wide variations between testes from single animals and between testes from different animals, whether sacrificed together or at different times of the year. Nevertheless, in all cases, both morphology and labelling patterns indicate that spermatogenesis is continuously active. The variation observed in individual testes appears to be the result of waves of non-random entry of spermatogonial stem cells into the population of cells irreversibly committed to differentiation.", "contents": "Morphology and kinetics of spermatogenesis in Xenopus laevis. The light microscopic characteristics of spermatogenic stages of the germ cell line in the anuran, Xenopus laevis, have been described as they appear in both nuclear squash preparations and plastic embedded thick sections of intact testes. Tritiated thymidine autoradiography was employed to unequivocally identify stages. Using this methodology, it was determined that the premeiotic DNA synthetic period occurs in a cell which is morphologically indistinguishable from a late secondary spermatogonial cell. In addition, kinetic studies with tritiated thymidine were employed to determine the duration of meiotic prophase and spermiogenesis in Xenopus. Results indicate that at 18 degrees C, the most rapidly matururing cells in the testis spend four days in leptotene, six days in zygotene, twelve days in pachytene, one day in diplotene, one day in meiotic division, and twelve days in spermiogenesis. An estimate for the duration of the premeiotic S stage was indirectly calculated from combined data to yield a value of six to seven days. Pooled spermatocyte counts measuring the frequency of occurrence of individual stages produced results which correlated closely with estimates obtained by tritiated thymidine labelling. Individual counts, however, show wide variations between testes from single animals and between testes from different animals, whether sacrificed together or at different times of the year. Nevertheless, in all cases, both morphology and labelling patterns indicate that spermatogenesis is continuously active. The variation observed in individual testes appears to be the result of waves of non-random entry of spermatogonial stem cells into the population of cells irreversibly committed to differentiation."} {"id": "PMID:1262822", "title": "In vivo and in vitro fertilization of hamster, rat and mouse eggs after treatment with anti-hamster ovary antiserum.", "content": "Rabbit antiserum against hamster ovary was examined on agargel diffusion plates against several hamster tissues, and also against rat and mouse ovarian extracts. Unabsorbed anti-hamster ovary antiserum showed eight to nine precipitin bands for hamster ovary and four to eight bands for other tissue extracts, but no bands against sperm antigens. Anti-hamster ovary antiserum also showed three to four bands for rat and one to two bands for mouse ovarian extracts. The present experiments confirmed previous reports for the hamster and mouse that treatment of eggs with anti-ovary antiserum blocked in vitro fertilization and that the extent of the inhibition was related to the formation of a precipitate on the zone pellucida. A single injection of anti-hamster ovary antiserum inhibited fertilization in mice but not in rats. In vitro fertilization of mouse eggs was also inhibited in the presence of such antiserum.", "contents": "In vivo and in vitro fertilization of hamster, rat and mouse eggs after treatment with anti-hamster ovary antiserum. Rabbit antiserum against hamster ovary was examined on agargel diffusion plates against several hamster tissues, and also against rat and mouse ovarian extracts. Unabsorbed anti-hamster ovary antiserum showed eight to nine precipitin bands for hamster ovary and four to eight bands for other tissue extracts, but no bands against sperm antigens. Anti-hamster ovary antiserum also showed three to four bands for rat and one to two bands for mouse ovarian extracts. The present experiments confirmed previous reports for the hamster and mouse that treatment of eggs with anti-ovary antiserum blocked in vitro fertilization and that the extent of the inhibition was related to the formation of a precipitate on the zone pellucida. A single injection of anti-hamster ovary antiserum inhibited fertilization in mice but not in rats. In vitro fertilization of mouse eggs was also inhibited in the presence of such antiserum."} {"id": "PMID:1262823", "title": "Gallium-67 distribution in pregnant mammals.", "content": "Studies on the distribution of 67Ga in pregnant rabbits showed a marked concentration of the isotope in uterine tissue and flushings of 5-day pregnant rabbits 24 hours after isotope injection. The isotope no longer localized throughout the uterine tissues and flushings on injection of 7- to 8-day pregnant rabbits but was specifically associated with the blastocysts and sites of implantation. As the gestation time progressed 67Ga increasingly concentrated in placental and mammary tissue while the concentration in serum and thymus tissue decreased. The marked concentration in placental tissue was readily discernible on total-body scans of pregnant rabbits. Column chromatography of uterine washings and placental extracts from pregnant rabbits and thymus extracts from estrous rabbits showed most of the isotope associated with moieties greater than or equal to 200,000 MW whereas the isotope in \"milk\" and extracts of mammary tissue was bound to components of 25,000-35,000 MW. Extracts of thymus from pregnant rats showed a marked, selective loss of 67Ga binding in two peaks of approximately 50,000 and 120,000 MW compared to the chromatographic profile of extracts from normal rat thymus.", "contents": "Gallium-67 distribution in pregnant mammals. Studies on the distribution of 67Ga in pregnant rabbits showed a marked concentration of the isotope in uterine tissue and flushings of 5-day pregnant rabbits 24 hours after isotope injection. The isotope no longer localized throughout the uterine tissues and flushings on injection of 7- to 8-day pregnant rabbits but was specifically associated with the blastocysts and sites of implantation. As the gestation time progressed 67Ga increasingly concentrated in placental and mammary tissue while the concentration in serum and thymus tissue decreased. The marked concentration in placental tissue was readily discernible on total-body scans of pregnant rabbits. Column chromatography of uterine washings and placental extracts from pregnant rabbits and thymus extracts from estrous rabbits showed most of the isotope associated with moieties greater than or equal to 200,000 MW whereas the isotope in \"milk\" and extracts of mammary tissue was bound to components of 25,000-35,000 MW. Extracts of thymus from pregnant rats showed a marked, selective loss of 67Ga binding in two peaks of approximately 50,000 and 120,000 MW compared to the chromatographic profile of extracts from normal rat thymus."} {"id": "PMID:1262824", "title": "The forensic taxonomic debate on Cannabis: semantic hokum.", "content": "It has been asserted that there are legal species of marihuana plants, and this contention has generated frequent court challenges of criminal prosecutions involving marihuana. Invariably the claim is made that the name C. sativa used in legislation is insufficiently comprehensive to proscribe all forms of marihuana. The maneuver being used, alarmingly, is potentially applicable to innumerable other materials, but its success is based on a failure to appreciate the subjective nature of taxonomy and the little-known but critical ambiguities which are inherent in scientific names. The complex principles and operational conventions of biological nomenclature are presented in elementary fashion. Despite important technical constraints on the use of scientific names, some facts are clear: these names are used subjectively, they may be highly ambiguous, the consensus on use of these names is liable to change with time and, most important, quite permissibly they may have substantially different meanings to different users. The claim that there are legal species of Cannabis merely amounts to a semantic ploy in which certain of the variants of Cannabis that have customarily been understood to be denoted by the species name C. sativa, and which are clearly understood to be proscribed, are simply arbitrarily redefined as different species. This ploy has proven unsuccessful in all cases where scientific evidence was adequately presented by the state and in all important court cases where the issue was critically examined.", "contents": "The forensic taxonomic debate on Cannabis: semantic hokum. It has been asserted that there are legal species of marihuana plants, and this contention has generated frequent court challenges of criminal prosecutions involving marihuana. Invariably the claim is made that the name C. sativa used in legislation is insufficiently comprehensive to proscribe all forms of marihuana. The maneuver being used, alarmingly, is potentially applicable to innumerable other materials, but its success is based on a failure to appreciate the subjective nature of taxonomy and the little-known but critical ambiguities which are inherent in scientific names. The complex principles and operational conventions of biological nomenclature are presented in elementary fashion. Despite important technical constraints on the use of scientific names, some facts are clear: these names are used subjectively, they may be highly ambiguous, the consensus on use of these names is liable to change with time and, most important, quite permissibly they may have substantially different meanings to different users. The claim that there are legal species of Cannabis merely amounts to a semantic ploy in which certain of the variants of Cannabis that have customarily been understood to be denoted by the species name C. sativa, and which are clearly understood to be proscribed, are simply arbitrarily redefined as different species. This ploy has proven unsuccessful in all cases where scientific evidence was adequately presented by the state and in all important court cases where the issue was critically examined."} {"id": "PMID:1262825", "title": "Detection of urinary Cannabis metabolites: a preliminary investigation.", "content": "Cannabinol and 11-OH-delta9-THC have been detected in the individual urines of five professed marihuana or hashish smokers. Both compounds exist primarily as urinary conjugates with the concentration of cannabinol being substantially greater than 11-OH-delta9-THC in all urines. These findings are discussed in light of present knowledge of delta9-THC metabolism and in view of current analytical procedures for the determination of delta9-THC and its metabolites in physiological fluids.", "contents": "Detection of urinary Cannabis metabolites: a preliminary investigation. Cannabinol and 11-OH-delta9-THC have been detected in the individual urines of five professed marihuana or hashish smokers. Both compounds exist primarily as urinary conjugates with the concentration of cannabinol being substantially greater than 11-OH-delta9-THC in all urines. These findings are discussed in light of present knowledge of delta9-THC metabolism and in view of current analytical procedures for the determination of delta9-THC and its metabolites in physiological fluids."} {"id": "PMID:1262826", "title": "Extraction procedures for some common drugs in clinical and forensic toxicology.", "content": "The results of four extraction systems for 86 drugs are reported. These systems were investigated with the view to obtaining a rapid, reliable, and efficient extraction technique in clinical and forensic toxicology.", "contents": "Extraction procedures for some common drugs in clinical and forensic toxicology. The results of four extraction systems for 86 drugs are reported. These systems were investigated with the view to obtaining a rapid, reliable, and efficient extraction technique in clinical and forensic toxicology."} {"id": "PMID:1262827", "title": "A fatal case involving proparacaine.", "content": "A 16-year-old female died soon after inhaling proparacaine. Analysis of the tissues revealed an amphoteric compound consistent with a hydrolysis product prepared in the laboratory by reacting proparacaine with HCl in the presence of heat.", "contents": "A fatal case involving proparacaine. A 16-year-old female died soon after inhaling proparacaine. Analysis of the tissues revealed an amphoteric compound consistent with a hydrolysis product prepared in the laboratory by reacting proparacaine with HCl in the presence of heat."} {"id": "PMID:1262828", "title": "Mass spectrometry as an aid in the detection and identification of piperidyl benzilates and related glycolates.", "content": "On the basis of the data presented above the following conclusions may be drawn. 1. The molecular ion peaks of most of the compounds examined are relatively weak but usually easily discernible to permit molecular weight determination. 2. The mass spectra of benzilate esters exhibit a relatively intense peak at m/e 183, and monitoring of this ion can serve as a means for preliminary screening for the presence of this type of a system. 3. Related esters exhibit a similar type of fragmentation resulting in a fragment ion analogous to m/e 183 but shifted by the appropriate number of mass units according to the substituents present. 4. Cleavage of the piperidine ring-ester oxygen bond in 3 and 4-substituted isomers is followed by selective losses of hydrogen radicals to produce ions of type e, f, and g as indicated above. It is significant that in a related piperidine ring system (methylphenidate) substituted in the 2 position, the same type of cleavage results in no further hydrogen losses [16] because of charge stabilization from the ring nitrogen (ion j, Fig. 17) [17]. In other words, the tendency to form a conjugated ion following initial bond cleavage can serve as a means for identifying the position of substitution on the ring and for distinguishing positional isomers.", "contents": "Mass spectrometry as an aid in the detection and identification of piperidyl benzilates and related glycolates. On the basis of the data presented above the following conclusions may be drawn. 1. The molecular ion peaks of most of the compounds examined are relatively weak but usually easily discernible to permit molecular weight determination. 2. The mass spectra of benzilate esters exhibit a relatively intense peak at m/e 183, and monitoring of this ion can serve as a means for preliminary screening for the presence of this type of a system. 3. Related esters exhibit a similar type of fragmentation resulting in a fragment ion analogous to m/e 183 but shifted by the appropriate number of mass units according to the substituents present. 4. Cleavage of the piperidine ring-ester oxygen bond in 3 and 4-substituted isomers is followed by selective losses of hydrogen radicals to produce ions of type e, f, and g as indicated above. It is significant that in a related piperidine ring system (methylphenidate) substituted in the 2 position, the same type of cleavage results in no further hydrogen losses [16] because of charge stabilization from the ring nitrogen (ion j, Fig. 17) [17]. In other words, the tendency to form a conjugated ion following initial bond cleavage can serve as a means for identifying the position of substitution on the ring and for distinguishing positional isomers."} {"id": "PMID:1262829", "title": "Elemental analysis by energy dispersive x-ray: a significant factor in the forensic analysis of glass.", "content": "Eighty-one glass samples were analyzed by EDX; two were indistinguishable. However, when the physical properties of the glass samples were considered, all glass samples were distinguishable from each other. The need to examine glass with respect not only to physical properties but also to elemental composition has been demonstrated. The authors believe that if glass is examined only by density and refractive indexes it is quite possible to conclude incorrectly that glass samples with the same physical qualities could have originated from the same source. To confirm that the glass specimens may have in fact originated from the same source their elemental compositions in addition to density and refractive indexes must be determined. The analysis by EDX of glass samples can selectively eliminate most specimens on the basis of elemental differences. If this step is performed prior to refractive index or density measurements considerable time savings can be realized in casework situations.", "contents": "Elemental analysis by energy dispersive x-ray: a significant factor in the forensic analysis of glass. Eighty-one glass samples were analyzed by EDX; two were indistinguishable. However, when the physical properties of the glass samples were considered, all glass samples were distinguishable from each other. The need to examine glass with respect not only to physical properties but also to elemental composition has been demonstrated. The authors believe that if glass is examined only by density and refractive indexes it is quite possible to conclude incorrectly that glass samples with the same physical qualities could have originated from the same source. To confirm that the glass specimens may have in fact originated from the same source their elemental compositions in addition to density and refractive indexes must be determined. The analysis by EDX of glass samples can selectively eliminate most specimens on the basis of elemental differences. If this step is performed prior to refractive index or density measurements considerable time savings can be realized in casework situations."} {"id": "PMID:1262830", "title": "Preparing samples for the recording of infrared spectra from synthetic fibers.", "content": "An improved technique for recording infrared spectra from minute amounts of synthetic fibers by using KBr micropellets is described. The procedure is the same for all commonly encountered synthetic fiber varieties; hence, no preliminary identification is required.", "contents": "Preparing samples for the recording of infrared spectra from synthetic fibers. An improved technique for recording infrared spectra from minute amounts of synthetic fibers by using KBr micropellets is described. The procedure is the same for all commonly encountered synthetic fiber varieties; hence, no preliminary identification is required."} {"id": "PMID:1262831", "title": "Concentrations of ethanol in two segments of the vascular system.", "content": "The time courses of capillary and venous blood concentrations of ethanol after oral administration of 0.30 and 0.34 g/kg doses of ethanol to two normal human subjects indicated that, by interpolation, equal capillary and venous concentrations are reached at only one time, and this time varied with the subject. The capillary/venous blood concentration ratios varied markedly as a function of time in both subjects over the entire observation period of 4 h.", "contents": "Concentrations of ethanol in two segments of the vascular system. The time courses of capillary and venous blood concentrations of ethanol after oral administration of 0.30 and 0.34 g/kg doses of ethanol to two normal human subjects indicated that, by interpolation, equal capillary and venous concentrations are reached at only one time, and this time varied with the subject. The capillary/venous blood concentration ratios varied markedly as a function of time in both subjects over the entire observation period of 4 h."} {"id": "PMID:1262833", "title": "The computer and the law: coordinate analysis of skull shape and possible methods of postmortem identification.", "content": "Mechanisms accelerating or retarding the disintegration of soft tissues are briefly discussed, as well as the need to reconstruct the missing profile for postmortem identification purposes. The application of X-ray and computer-based analyses is discussed in the context of providing data to predict and reconstruct the most probable soft tissue profile of a dry skull. In addition, information from extensive studies of the facial bones and profiles of veterans has been applied to methods in forensic medicine of determining age, sex, and racial background of unknown subjects.", "contents": "The computer and the law: coordinate analysis of skull shape and possible methods of postmortem identification. Mechanisms accelerating or retarding the disintegration of soft tissues are briefly discussed, as well as the need to reconstruct the missing profile for postmortem identification purposes. The application of X-ray and computer-based analyses is discussed in the context of providing data to predict and reconstruct the most probable soft tissue profile of a dry skull. In addition, information from extensive studies of the facial bones and profiles of veterans has been applied to methods in forensic medicine of determining age, sex, and racial background of unknown subjects."} {"id": "PMID:1262834", "title": "An experimental study of powder tattooing of the skin.", "content": "Test firings were conducted on specially prepared live rabbits to determine the approximate maximum ranges at which powder tattooing occurs for different forms of gunpowder. For .38 caliber, powder tattooing from cartridges loaded with flake powder disappears at a range of 18 to 24 in. (0.4 to 0.6 m). Powder tattooing with flattened ball powder extends to 36 in. (0.9 m), while that due to ball powder extends to 48 in. (1.2m) of range. In .22 caliber, powder tattooing was observed out to 24 in. (0.6 m) with flake powder and 18 in. (0.4 m) with flattened ball. Attempts to reproduce the animal powder tattoo patterns on paper revealed that the paper patterns are consistent with skin tattoo patterns only up to 18 in (0.4 m) of range.", "contents": "An experimental study of powder tattooing of the skin. Test firings were conducted on specially prepared live rabbits to determine the approximate maximum ranges at which powder tattooing occurs for different forms of gunpowder. For .38 caliber, powder tattooing from cartridges loaded with flake powder disappears at a range of 18 to 24 in. (0.4 to 0.6 m). Powder tattooing with flattened ball powder extends to 36 in. (0.9 m), while that due to ball powder extends to 48 in. (1.2m) of range. In .22 caliber, powder tattooing was observed out to 24 in. (0.6 m) with flake powder and 18 in. (0.4 m) with flattened ball. Attempts to reproduce the animal powder tattoo patterns on paper revealed that the paper patterns are consistent with skin tattoo patterns only up to 18 in (0.4 m) of range."} {"id": "PMID:1262835", "title": "Soft tissue radiography in determining contact and near-contact gunshot wounds.", "content": "Contact and near-contact gunshot wounds ordinarily show distinctive gunpowder patterns, muzzle imprints, or tearing of the skin. Microscopic and chemical examination have been used to estimate firing distances. A new method that utilizes soft tissue radiography is described. Nonjacketed lead bullets deposit a pattern of fragments and residues in tissue circumscribing contact and close gunshot wounds. Various patterns are presented to contrast the appearance of contact from distant gunshot wounds using various firearms and different types of bullets. This procedure may be used as an adjunct in the determination of contact and close gunshot wounds.", "contents": "Soft tissue radiography in determining contact and near-contact gunshot wounds. Contact and near-contact gunshot wounds ordinarily show distinctive gunpowder patterns, muzzle imprints, or tearing of the skin. Microscopic and chemical examination have been used to estimate firing distances. A new method that utilizes soft tissue radiography is described. Nonjacketed lead bullets deposit a pattern of fragments and residues in tissue circumscribing contact and close gunshot wounds. Various patterns are presented to contrast the appearance of contact from distant gunshot wounds using various firearms and different types of bullets. This procedure may be used as an adjunct in the determination of contact and close gunshot wounds."} {"id": "PMID:1262837", "title": "Sex-chromatin bodies in penile washings as an indicator of recent coitus.", "content": "A technique for the collection and examination of penile washings for the possible presence of vaginal cells is presented. Various characteristics of cellular form and structure are discussed insofar as they pertain to the primary goal of this study--the detection of evidence of recent sexual intercourse on the part of a male by the examination of cellular content of penile washings.", "contents": "Sex-chromatin bodies in penile washings as an indicator of recent coitus. A technique for the collection and examination of penile washings for the possible presence of vaginal cells is presented. Various characteristics of cellular form and structure are discussed insofar as they pertain to the primary goal of this study--the detection of evidence of recent sexual intercourse on the part of a male by the examination of cellular content of penile washings."} {"id": "PMID:1262840", "title": "Excepted substances: a comparison of Federal and state laws.", "content": "A state law has placed an obligation on the criminal investigation laboratories to screen and quantitate all preparations, both pharmaceutical and illicit, that fall under the provisions of \"Excepted Substances.\" Without complete screens on these preparations, there is room for erroneous indictments as well as possible acquittals on technicalities.", "contents": "Excepted substances: a comparison of Federal and state laws. A state law has placed an obligation on the criminal investigation laboratories to screen and quantitate all preparations, both pharmaceutical and illicit, that fall under the provisions of \"Excepted Substances.\" Without complete screens on these preparations, there is room for erroneous indictments as well as possible acquittals on technicalities."} {"id": "PMID:1262843", "title": "A potential young murderer.", "content": "Longitudinal study of six people who committed homicides or exhibited a potential for homicidal behavior was undertaken over a period of ten years. The data were obtained through psychiatric interviews, psychological testing, and examination of all available records. The material thus obtained was analyzed from the psychoanalytic point of view. Three specific points were identified as being common and applicable to a lesser or greater degree in all six cases studied. First, as children each of these six people suffered actual physical abuse perpetrated by their parents. Second, they actually saw during childhood violent and destructive behavior by their parents. Third, the sequelae of such exposure to violence interfered with the phase specific resolution of the basic conflicts of childhood, specifically Oedipus complex. These traumata of violence set up a predisposition for regression to the preoedipal levels of psychic organization and functioning. From the structural point of view, ego functions of impulse control were lacking due to profound states of regression whenever these patients experienced extreme anger, which in turn would precipitate homicidal behavior. None of the patients had childhood history of pyromania, enuresis, nor cruelty to animals. On the basis of the aforegoing material, one may conclude that in some instances it is possible to establish \"homicidal proneness\" as a clinical entity. Homicidal proneness can be anticipated in people who as children suffered from physical and emotional abuse, witnessed violence, and were sexually traumatized through incestuous experiences or their equivalents.", "contents": "A potential young murderer. Longitudinal study of six people who committed homicides or exhibited a potential for homicidal behavior was undertaken over a period of ten years. The data were obtained through psychiatric interviews, psychological testing, and examination of all available records. The material thus obtained was analyzed from the psychoanalytic point of view. Three specific points were identified as being common and applicable to a lesser or greater degree in all six cases studied. First, as children each of these six people suffered actual physical abuse perpetrated by their parents. Second, they actually saw during childhood violent and destructive behavior by their parents. Third, the sequelae of such exposure to violence interfered with the phase specific resolution of the basic conflicts of childhood, specifically Oedipus complex. These traumata of violence set up a predisposition for regression to the preoedipal levels of psychic organization and functioning. From the structural point of view, ego functions of impulse control were lacking due to profound states of regression whenever these patients experienced extreme anger, which in turn would precipitate homicidal behavior. None of the patients had childhood history of pyromania, enuresis, nor cruelty to animals. On the basis of the aforegoing material, one may conclude that in some instances it is possible to establish \"homicidal proneness\" as a clinical entity. Homicidal proneness can be anticipated in people who as children suffered from physical and emotional abuse, witnessed violence, and were sexually traumatized through incestuous experiences or their equivalents."} {"id": "PMID:1262852", "title": "Ionic selectivity of the sodium channel of frog skeletal muscle.", "content": "The ionic selectivity of the Na channel to a variety of metal and organic cations is studied in frog semitendinosus muscle. Na channel currents are measured under voltage clamp conditions in fibers bathed in solutions with all Na+ replaced by a test ion. Permeability ratios are calculated from measured reversal potentials using the Goldman-Hodgkin-Katz equation. The permeability sequence was Na+ approximately Li+ approximately hydroxylammonium greater than hydrazinium greater than ammonium greater than guanidinium greater than K+ greater than aminoguanidinium in the ratios 1:0.96:0.94:0.31:0.11:0.093:0.048:0.031. No inward currents were observed for Ca++, methylammonium, methylguanidinium, tetraethylammonium, and tetramethylammonium. The results are consistent with the Hille model of the Na channel selectivity filter of the node of Ranvier and suggest that the selectivity filter of the two channels is the same.", "contents": "Ionic selectivity of the sodium channel of frog skeletal muscle. The ionic selectivity of the Na channel to a variety of metal and organic cations is studied in frog semitendinosus muscle. Na channel currents are measured under voltage clamp conditions in fibers bathed in solutions with all Na+ replaced by a test ion. Permeability ratios are calculated from measured reversal potentials using the Goldman-Hodgkin-Katz equation. The permeability sequence was Na+ approximately Li+ approximately hydroxylammonium greater than hydrazinium greater than ammonium greater than guanidinium greater than K+ greater than aminoguanidinium in the ratios 1:0.96:0.94:0.31:0.11:0.093:0.048:0.031. No inward currents were observed for Ca++, methylammonium, methylguanidinium, tetraethylammonium, and tetramethylammonium. The results are consistent with the Hille model of the Na channel selectivity filter of the node of Ranvier and suggest that the selectivity filter of the two channels is the same."} {"id": "PMID:1262853", "title": "Electromechanical coupling in tubular muscle fibers. II. Resistance and capacitance of one transverse tubule.", "content": "In tubular muscle fibers of the yellow scorpion the transverse tubules are arranged in a radial symmetry. This particular morphology, enables one to derive values for electrical components of one transverse tubule (TT) by treating the TT as a core conductor rather than a complex network. The electrical properties of tubular muscle fibers were completely characterized and analyzed by measuring two independent functions of frequency, i.e., the characteristic impedance and the propagation function. The impedance of a single tubular muscle fiber was determined with microelectrodes over the frequency range 1 Hz to 1.5 kHz. The results were fitted to a possible equivalent circuit model which is based on morphological evidence. The average component values for this model are: Ri = 209 omega-cm, Rm, and RT = 980 omega-cm2 (referred to unit area of surface membrane), Cm and CT = 0.9 muF/cm2, and RL = 103 omega-cm. Relating the equivalent circuit to ultrastructure shows that the average component values are consistent with the hypothesis that the TT is open to the extracellular medium, the electrical capacity of surface and TT membranes is about 1 muF/cm2, and the spread of surface depolarization into the TT is attenuated by about 25%.", "contents": "Electromechanical coupling in tubular muscle fibers. II. Resistance and capacitance of one transverse tubule. In tubular muscle fibers of the yellow scorpion the transverse tubules are arranged in a radial symmetry. This particular morphology, enables one to derive values for electrical components of one transverse tubule (TT) by treating the TT as a core conductor rather than a complex network. The electrical properties of tubular muscle fibers were completely characterized and analyzed by measuring two independent functions of frequency, i.e., the characteristic impedance and the propagation function. The impedance of a single tubular muscle fiber was determined with microelectrodes over the frequency range 1 Hz to 1.5 kHz. The results were fitted to a possible equivalent circuit model which is based on morphological evidence. The average component values for this model are: Ri = 209 omega-cm, Rm, and RT = 980 omega-cm2 (referred to unit area of surface membrane), Cm and CT = 0.9 muF/cm2, and RL = 103 omega-cm. Relating the equivalent circuit to ultrastructure shows that the average component values are consistent with the hypothesis that the TT is open to the extracellular medium, the electrical capacity of surface and TT membranes is about 1 muF/cm2, and the spread of surface depolarization into the TT is attenuated by about 25%."} {"id": "PMID:1262854", "title": "Grayanotoxin, veratrine, and tetrodotoxin-sensitive sodium pathways in the Schwann cell membrane of squid nerve fibers.", "content": "The actions of grayanotoxin I, veratrine, and tetrodotoxin on the membrane potential of the Schwann cell were studied in the giant nerve fiber of the squid Sepioteuthis sepioidea. Schwann cells of intact nerve fibers and Schwann cells attached to axons cut lengthwise over several millimeters were utilized. The axon membrane potential in the intact nerve fibers was also monitored. The effects of grayanotoxin I and veratrine on the membrane potential of the Schwann cell were found to be similar to those they produce on the resting membrane potential of the giant axon. Thus, grayanotoxin I (1-30 muM) and veratrine (5-50 mug-jl-1), externally applied to the intact nerve fiber or to axon-free nerve fiber sheaths, produce a Schwann cell depolarization which can be reversed by decreasing the external sodium concentration or by external application of tetrodotoxin. The magnitude of these membrane potential changes is related to the concentrations of the drugs in the external medium. These results indicate the existence of sodium pathways in the electrically unexcitable Schwann cell membrane of S. sepioidea, which can be opened up by grayanotoxin I and veratrine, and afterwards are blocked by tetrodotoxin. The sodium pathways of the Schwann cell membrane appear to be different from those of the axolemma which show a voltage-dependent conductance.", "contents": "Grayanotoxin, veratrine, and tetrodotoxin-sensitive sodium pathways in the Schwann cell membrane of squid nerve fibers. The actions of grayanotoxin I, veratrine, and tetrodotoxin on the membrane potential of the Schwann cell were studied in the giant nerve fiber of the squid Sepioteuthis sepioidea. Schwann cells of intact nerve fibers and Schwann cells attached to axons cut lengthwise over several millimeters were utilized. The axon membrane potential in the intact nerve fibers was also monitored. The effects of grayanotoxin I and veratrine on the membrane potential of the Schwann cell were found to be similar to those they produce on the resting membrane potential of the giant axon. Thus, grayanotoxin I (1-30 muM) and veratrine (5-50 mug-jl-1), externally applied to the intact nerve fiber or to axon-free nerve fiber sheaths, produce a Schwann cell depolarization which can be reversed by decreasing the external sodium concentration or by external application of tetrodotoxin. The magnitude of these membrane potential changes is related to the concentrations of the drugs in the external medium. These results indicate the existence of sodium pathways in the electrically unexcitable Schwann cell membrane of S. sepioidea, which can be opened up by grayanotoxin I and veratrine, and afterwards are blocked by tetrodotoxin. The sodium pathways of the Schwann cell membrane appear to be different from those of the axolemma which show a voltage-dependent conductance."} {"id": "PMID:1262855", "title": "Isolation, properties and taxonomic relevance of lipid-soluble, iron-binding compounds (the nocobactins) from Nocardia.", "content": "Representative strains of the genus Nocardia, when grown on iron-deficient media, produce intracellular lipid-soluble, iron-binding compounds known as nocobactins. However, strains representing the 'rhodochrous' taxon fail to form such compounds. The formation of the nocobactins is completely repressed in bacteria grown on iron-sufficient media. Procedures for purifying the nocobactins are described. From their various properties (u.v. and visible spectra of the the ferri- and desferri-materials, mobility upon thin-layer chromatography, and dissociation patterns in HCl), they can be distinguished from the mycobactins (related compounds from mycobacteria) and divided into three main classes. The classes correspond to the three well-described species of the genus Norcardia: N. asteroides, N. brasiliensis and N. caviae. The correlation of the nocobactin data with previous results of conventional numerical taxonomy is high. Two strains of N. asteroides, however, did not produce nocobactins of the group type.", "contents": "Isolation, properties and taxonomic relevance of lipid-soluble, iron-binding compounds (the nocobactins) from Nocardia. Representative strains of the genus Nocardia, when grown on iron-deficient media, produce intracellular lipid-soluble, iron-binding compounds known as nocobactins. However, strains representing the 'rhodochrous' taxon fail to form such compounds. The formation of the nocobactins is completely repressed in bacteria grown on iron-sufficient media. Procedures for purifying the nocobactins are described. From their various properties (u.v. and visible spectra of the the ferri- and desferri-materials, mobility upon thin-layer chromatography, and dissociation patterns in HCl), they can be distinguished from the mycobactins (related compounds from mycobacteria) and divided into three main classes. The classes correspond to the three well-described species of the genus Norcardia: N. asteroides, N. brasiliensis and N. caviae. The correlation of the nocobactin data with previous results of conventional numerical taxonomy is high. Two strains of N. asteroides, however, did not produce nocobactins of the group type."} {"id": "PMID:1262856", "title": "Deoxyribonucleic acid reassociation in the classification of flavobacteria.", "content": "DNA-DNA reassociation studies showed that Flavobacterium emningosepticum strains had a genetic relatedness of 91 to 100% with inter-strain duplexes having high thermal stabilities. The only exception, strain NCTC10016, had an average relatedness of only 43% to other strains of F. meningosepticum. The apparent divergence in DNA base sequence of this strain was reflected in the structural differences of some enzymes. There was a gradation of DNA relatedness among the Flavobacterium group II-b strains, but three strains were sufficiently related to constitute a species. Low levels of genetic relatedness were confirmed between F. meningosepticum and strains of Flavobacterium group II-b, group II-f, F. aquatile, F. breve, F. heparinum, F. pectinovorum, F. odoratum and Moraxella saccharolytica. All strains had base compositions in the range 32 to 46% guanine plus cytosine. The genome sizes of representative strains of F. meningosepticum and Flavobacterium group II-b were 2-50 X 10(9) to 3-52 X 10(9) daltons. The taxonomic implications of these findings are discussed.", "contents": "Deoxyribonucleic acid reassociation in the classification of flavobacteria. DNA-DNA reassociation studies showed that Flavobacterium emningosepticum strains had a genetic relatedness of 91 to 100% with inter-strain duplexes having high thermal stabilities. The only exception, strain NCTC10016, had an average relatedness of only 43% to other strains of F. meningosepticum. The apparent divergence in DNA base sequence of this strain was reflected in the structural differences of some enzymes. There was a gradation of DNA relatedness among the Flavobacterium group II-b strains, but three strains were sufficiently related to constitute a species. Low levels of genetic relatedness were confirmed between F. meningosepticum and strains of Flavobacterium group II-b, group II-f, F. aquatile, F. breve, F. heparinum, F. pectinovorum, F. odoratum and Moraxella saccharolytica. All strains had base compositions in the range 32 to 46% guanine plus cytosine. The genome sizes of representative strains of F. meningosepticum and Flavobacterium group II-b were 2-50 X 10(9) to 3-52 X 10(9) daltons. The taxonomic implications of these findings are discussed."} {"id": "PMID:1262857", "title": "Conditions affecting boundary response to messages out of awareness.", "content": "Multiple studies evaluated the role of the following parameters in mediating the effects of auditory subliminal inputs upon the body boundary: being made aware that exposure to subliminal stimuli is occurring, nature of the priming preliminary to the input, length of exposure, competing sensory input, use of specialized content messages, tolerance for unrealistic experience, and masculinity-feminity. A test-retest design was typically employed that involved measuring the baseline Barrier score with the Holtzman bolts and then ascertaining the Barrier change when responding to a second series of Holtzman blots at the same time that subliminal input was occurring. Complex results emerged that defined in considerably new detail what facilitates and blocks the boundary-disrupting effects of subliminal messages in men and to a lesser degree in women.", "contents": "Conditions affecting boundary response to messages out of awareness. Multiple studies evaluated the role of the following parameters in mediating the effects of auditory subliminal inputs upon the body boundary: being made aware that exposure to subliminal stimuli is occurring, nature of the priming preliminary to the input, length of exposure, competing sensory input, use of specialized content messages, tolerance for unrealistic experience, and masculinity-feminity. A test-retest design was typically employed that involved measuring the baseline Barrier score with the Holtzman bolts and then ascertaining the Barrier change when responding to a second series of Holtzman blots at the same time that subliminal input was occurring. Complex results emerged that defined in considerably new detail what facilitates and blocks the boundary-disrupting effects of subliminal messages in men and to a lesser degree in women."} {"id": "PMID:1262858", "title": "Identity of emotional triggers in epilepsy.", "content": "This communication describes a technique of stimulated recall and video replay which has reduced the frequency of seizures in five epileptic patients. Each of the patients had long standing partial epilepsy with complex symptomatology of the psychomotor type. It was generally acknowledged that emotional factors played an important role in their poor seizure control. Previous psychotherapeutic efforts had been without benefit because ictal amnesia had erased the memory of the stressful antecedent message-input which had triggered the seizures. Creation of empathetically stressful responses to presentation of audio and video tape recordings of specific problematic social interactions was sufficient to induce seizures in these patients. Video tape recording of the seizure and the antecedant events provided by means by which the patients could acquire otherwise unrecognized or forgotten information. Once equipped with the identity of the specific emotional trigger, the patient could avoid the kinds of events which might be expected to induce a seizure and be better able to cope with threatening environmental cues when encountered in the future.", "contents": "Identity of emotional triggers in epilepsy. This communication describes a technique of stimulated recall and video replay which has reduced the frequency of seizures in five epileptic patients. Each of the patients had long standing partial epilepsy with complex symptomatology of the psychomotor type. It was generally acknowledged that emotional factors played an important role in their poor seizure control. Previous psychotherapeutic efforts had been without benefit because ictal amnesia had erased the memory of the stressful antecedent message-input which had triggered the seizures. Creation of empathetically stressful responses to presentation of audio and video tape recordings of specific problematic social interactions was sufficient to induce seizures in these patients. Video tape recording of the seizure and the antecedant events provided by means by which the patients could acquire otherwise unrecognized or forgotten information. Once equipped with the identity of the specific emotional trigger, the patient could avoid the kinds of events which might be expected to induce a seizure and be better able to cope with threatening environmental cues when encountered in the future."} {"id": "PMID:1262859", "title": "Treatment of chronic post-traumatic organic brain syndrome with dextroamphetamine: first reported case.", "content": "In view of its therapeutic efficacy in the treatment of children with minimal brain dysfunction syndrome, dextroamphetamine was administered to a young adult with a chronic organic brain syndrome secondary to cerebral trauma. That D-amphetamine was critical to the resulting marked diminution in confusion, paranoia, and deficit in short term memory was confirmed by the occurrence of a relapse coincident with placebo administration as part of a double blind evaluation. Amitriptylline appeared to potentiate the therapeutic effects of D-amphetamine. The results achieved, although observational and subjective in nature, warrant replication in controlled, quantitative clinical studies.", "contents": "Treatment of chronic post-traumatic organic brain syndrome with dextroamphetamine: first reported case. In view of its therapeutic efficacy in the treatment of children with minimal brain dysfunction syndrome, dextroamphetamine was administered to a young adult with a chronic organic brain syndrome secondary to cerebral trauma. That D-amphetamine was critical to the resulting marked diminution in confusion, paranoia, and deficit in short term memory was confirmed by the occurrence of a relapse coincident with placebo administration as part of a double blind evaluation. Amitriptylline appeared to potentiate the therapeutic effects of D-amphetamine. The results achieved, although observational and subjective in nature, warrant replication in controlled, quantitative clinical studies."} {"id": "PMID:1262860", "title": "Variation in monoamine oxidase activity in rat brain crude mitochondrial fractions prepared by rate zonal centrifugation.", "content": "Rat brain crude mitochondrial fractionated by rate zonal centrifugation using an iso-osmotic gradient of Ficoll and sucrose. The results demonstrated that the isolated fractions were biochemically heterogeneous with regard to the enzymes, monoamine oxidase (MAO), NADH dehydrogenase and succinate dehydrogenase. When the activity of MAO was plotted as % of the highest specific activity towards tyramine, kynuramine oxidation remained fairly constant in fractions 10 to 30 but tyramine and dopamine showed separate peaks of activity in fractions 21 and 32 respectively. Sonic oscillations of separated particulate fractions did not change the ratios of various monoamine deamination when compared to the intact particles.", "contents": "Variation in monoamine oxidase activity in rat brain crude mitochondrial fractions prepared by rate zonal centrifugation. Rat brain crude mitochondrial fractionated by rate zonal centrifugation using an iso-osmotic gradient of Ficoll and sucrose. The results demonstrated that the isolated fractions were biochemically heterogeneous with regard to the enzymes, monoamine oxidase (MAO), NADH dehydrogenase and succinate dehydrogenase. When the activity of MAO was plotted as % of the highest specific activity towards tyramine, kynuramine oxidation remained fairly constant in fractions 10 to 30 but tyramine and dopamine showed separate peaks of activity in fractions 21 and 32 respectively. Sonic oscillations of separated particulate fractions did not change the ratios of various monoamine deamination when compared to the intact particles."} {"id": "PMID:1262861", "title": "Apomorphine in the rat nucleus accumbens: effects on the synthesis of 5-hydroxytryptamine and noradrenaline, the motor activity and the body temperature.", "content": "Apomorphine (10 mug) was injected bilaterally into the nucleus accumbens or the neostriatum of rats. The application of apomorphine to the nucleus accumbens, but not to the neostriatum, enhanced the accumulation of 5-hydroxytryptophan in the central nervous system following inhibition of the aromatic L-amino acid decarboxylase. The effect was greatest in the brain stem particularly in the pons plus medulla oblongata. Similar but smaller rises were observed for the accumulation of DOPA in noradrenalinerich regions. The motor activity was increased and the body temperature was decreased by apomorphine in the nucleus accumbens, whereas smaller or no effects were obtained from the neostriatum.", "contents": "Apomorphine in the rat nucleus accumbens: effects on the synthesis of 5-hydroxytryptamine and noradrenaline, the motor activity and the body temperature. Apomorphine (10 mug) was injected bilaterally into the nucleus accumbens or the neostriatum of rats. The application of apomorphine to the nucleus accumbens, but not to the neostriatum, enhanced the accumulation of 5-hydroxytryptophan in the central nervous system following inhibition of the aromatic L-amino acid decarboxylase. The effect was greatest in the brain stem particularly in the pons plus medulla oblongata. Similar but smaller rises were observed for the accumulation of DOPA in noradrenalinerich regions. The motor activity was increased and the body temperature was decreased by apomorphine in the nucleus accumbens, whereas smaller or no effects were obtained from the neostriatum."} {"id": "PMID:1262862", "title": "Separation of pineal extracts by gelfiltration. IV. Isolation, location and identification from sheep pineals of three indoles, identical with 5-hydroxytryptophol, 5-methoxytryptophol and melatonin.", "content": "Aqueous extracts of sheep pineal bodies were separated on Sephadex G-25. A low molecular Sephadex G-25 fraction F4 was filtrated on Sephadex G-10. Several distinct peaks could be detected showing excitation and fluorescence maxima resembling those of indoles. A thinlayer chromatography study revealed that one Sephadex G-10 peak contained a spot identical with that of synthetic 5-methoxytryptophol, another a spot with the same Rf-values in different solvents as synthetic 5-hydroxytryptophol, while from a third peak a substance was isolated identical with synthetic melatonin. Mass spectra of the isolated compounds were recorded. These results are compared with those of previous isolation studies.", "contents": "Separation of pineal extracts by gelfiltration. IV. Isolation, location and identification from sheep pineals of three indoles, identical with 5-hydroxytryptophol, 5-methoxytryptophol and melatonin. Aqueous extracts of sheep pineal bodies were separated on Sephadex G-25. A low molecular Sephadex G-25 fraction F4 was filtrated on Sephadex G-10. Several distinct peaks could be detected showing excitation and fluorescence maxima resembling those of indoles. A thinlayer chromatography study revealed that one Sephadex G-10 peak contained a spot identical with that of synthetic 5-methoxytryptophol, another a spot with the same Rf-values in different solvents as synthetic 5-hydroxytryptophol, while from a third peak a substance was isolated identical with synthetic melatonin. Mass spectra of the isolated compounds were recorded. These results are compared with those of previous isolation studies."} {"id": "PMID:1262863", "title": "An ultrastructural study of sympathetic ganglion satellite cells in the rat. 2. Effect of preganglionic sympathectomy.", "content": "The ultrastructure of satellite cells of the rat superior cervical ganglion was studied following preganglionic sympathectomy.Several distinct morphological alterations were observed: (a) enlargement of the intercellular space between the ganglion cells and the satellite cells, (b) dilation of the granular endoplasmic reticulum and loss of attached ribosomes, and (c) swelling of the mitochondria with disorganization of the cristae mitochondriales. The presence of degenerating nerve fibers and synaptic boutons was also noted.", "contents": "An ultrastructural study of sympathetic ganglion satellite cells in the rat. 2. Effect of preganglionic sympathectomy. The ultrastructure of satellite cells of the rat superior cervical ganglion was studied following preganglionic sympathectomy.Several distinct morphological alterations were observed: (a) enlargement of the intercellular space between the ganglion cells and the satellite cells, (b) dilation of the granular endoplasmic reticulum and loss of attached ribosomes, and (c) swelling of the mitochondria with disorganization of the cristae mitochondriales. The presence of degenerating nerve fibers and synaptic boutons was also noted."} {"id": "PMID:1262864", "title": "Plethysmographic study in the patients with non-specific complaints in the head-cervico-brachial regions: with a special reference to laterality in vasomotor responses and \"cervical sympathetic dysharmony\".", "content": "Bilateral vasomotor responses and sweat gland activities under the control of cervical sympathetic nerves were examined simultaneously by photo-electric plethysmogram (PTG) and skin potential reflex (SPR) in patients with nonspecific complaints in the head-cervicobrachial regions such as headache, dizziness, tinnitus, pain or stiffness of the neck and shoulder, and dullness or numbness of the arms. 137 out of those 355 patients (38.6%) were revealed to have laterality in vasomotor responses, but it was only 3 in 60 normal control subjects (5%) that showed the laterality in vasomotor responses. These results supported the assumption that the cervical sympathetic dysharmony--imbalance between the right and left sides of cervical sympathetic functions--played an important role in causing their various vegetative complaints in the head-cervicobrachial regions.", "contents": "Plethysmographic study in the patients with non-specific complaints in the head-cervico-brachial regions: with a special reference to laterality in vasomotor responses and \"cervical sympathetic dysharmony\". Bilateral vasomotor responses and sweat gland activities under the control of cervical sympathetic nerves were examined simultaneously by photo-electric plethysmogram (PTG) and skin potential reflex (SPR) in patients with nonspecific complaints in the head-cervicobrachial regions such as headache, dizziness, tinnitus, pain or stiffness of the neck and shoulder, and dullness or numbness of the arms. 137 out of those 355 patients (38.6%) were revealed to have laterality in vasomotor responses, but it was only 3 in 60 normal control subjects (5%) that showed the laterality in vasomotor responses. These results supported the assumption that the cervical sympathetic dysharmony--imbalance between the right and left sides of cervical sympathetic functions--played an important role in causing their various vegetative complaints in the head-cervicobrachial regions."} {"id": "PMID:1262865", "title": "The role of the autonomic nervous system in trigeminal neuralgia.", "content": "The role of the autonomic nervous system in trigeminal neuralgia is discussed. While the trigeminal nerve is accompanied by both sympathetic and parasympathetic fibers, first and second branch phenomena are predominantly associated with sympathetic stimuli. Third branch phenomena, by contrast, primarily involved a parasympathetic component. Atropine sulfate and beta-receptor blockers are suggested as a therapeutic modality. On ancillary studies involving 30 patients with trigeminal neuralgia an abnormal glucose tolerance and/or increased cholesterol level was found to be present in 28 cases.", "contents": "The role of the autonomic nervous system in trigeminal neuralgia. The role of the autonomic nervous system in trigeminal neuralgia is discussed. While the trigeminal nerve is accompanied by both sympathetic and parasympathetic fibers, first and second branch phenomena are predominantly associated with sympathetic stimuli. Third branch phenomena, by contrast, primarily involved a parasympathetic component. Atropine sulfate and beta-receptor blockers are suggested as a therapeutic modality. On ancillary studies involving 30 patients with trigeminal neuralgia an abnormal glucose tolerance and/or increased cholesterol level was found to be present in 28 cases."} {"id": "PMID:1262866", "title": "The isolated perfused chicken heart as a tool for studying acetylcholine output in the absence of cholinesterase inhibition.", "content": "In chicken hearts, the acetylcholine (ACh) output in response to vagal stimulation was easily detectable by gas chromatography even in the absence of cholinesterase inhibition. Eserine 10(-6) M markedly increased the ACh output. In contrast, the ACh output from the perfused rabbit heart was not measurable in the absence of cholinesterase inhibition. Both ACh concentration and cholinesterase activity were higher in the chicken heart than in the rabbit heart. In conclusion, the isolated perfused chicken heart is at present a unique tool for studying the output of the parasympathetic transmitter in the absence of cholinesterase inhibition.", "contents": "The isolated perfused chicken heart as a tool for studying acetylcholine output in the absence of cholinesterase inhibition. In chicken hearts, the acetylcholine (ACh) output in response to vagal stimulation was easily detectable by gas chromatography even in the absence of cholinesterase inhibition. Eserine 10(-6) M markedly increased the ACh output. In contrast, the ACh output from the perfused rabbit heart was not measurable in the absence of cholinesterase inhibition. Both ACh concentration and cholinesterase activity were higher in the chicken heart than in the rabbit heart. In conclusion, the isolated perfused chicken heart is at present a unique tool for studying the output of the parasympathetic transmitter in the absence of cholinesterase inhibition."} {"id": "PMID:1262867", "title": "The metabolism of adenine derivatives in different parts of the brain of the rat, and their release from hypothalamic preparations on excitation.", "content": "Five enzymes concerned with the metabolism of adenine derivatives were assayed in seven regions of the rat brain. A region which included the hypothalamus had the highest AMP deaminase and adenosine deaminase activities, while its 5'-nucleotidase activities were relatively low. The enzymes named and also the uptake of [14C]adenine by incubated tissue samples were more active with hypothalamic than with neocortical tissues. On superfusion with glucose-bicarbonate saline after assimilating [14C]adenine, the hypothalamic tissues released about 0.2 per cent of their 14C content per minute. This release was increased fourfold with electrical excitation but the presence of 0.25 muM tetrodotoxin prevented most of this increase. The compounds released during superfusion and electrical stimulation were preponderantly hypoxanthine, inosine, and adenosine, with only small amounts of adenine nucleotides. The output of all these compounds increased during the period of stimulation and also the proportion of adenine nucleotides increased when stimulation was carried out in the presence of tetrodotoxin. The output of the nucleotides and adenosine increased more promptly when stimulated than did that of the other compounds named. The results are discussed in terms of the metabolic roles of the enzymes concerned. and in relation to whether the enzymes are acting on intracellular or extracellular substrates.", "contents": "The metabolism of adenine derivatives in different parts of the brain of the rat, and their release from hypothalamic preparations on excitation. Five enzymes concerned with the metabolism of adenine derivatives were assayed in seven regions of the rat brain. A region which included the hypothalamus had the highest AMP deaminase and adenosine deaminase activities, while its 5'-nucleotidase activities were relatively low. The enzymes named and also the uptake of [14C]adenine by incubated tissue samples were more active with hypothalamic than with neocortical tissues. On superfusion with glucose-bicarbonate saline after assimilating [14C]adenine, the hypothalamic tissues released about 0.2 per cent of their 14C content per minute. This release was increased fourfold with electrical excitation but the presence of 0.25 muM tetrodotoxin prevented most of this increase. The compounds released during superfusion and electrical stimulation were preponderantly hypoxanthine, inosine, and adenosine, with only small amounts of adenine nucleotides. The output of all these compounds increased during the period of stimulation and also the proportion of adenine nucleotides increased when stimulation was carried out in the presence of tetrodotoxin. The output of the nucleotides and adenosine increased more promptly when stimulated than did that of the other compounds named. The results are discussed in terms of the metabolic roles of the enzymes concerned. and in relation to whether the enzymes are acting on intracellular or extracellular substrates."} {"id": "PMID:1262868", "title": "Movement of glycine across the blood-brain barrier of the rabbit.", "content": "The single pass clearance of glycine from the cerebral capillary bed was measured in the rabbit with the indicator diffusion method. It was shown that glycine was extracted to the same degree as fructose (ca..07). The concentration of glycine injected into the carotid artery was varied some 700-fold without significantly affecting the clearance of this amino acid in transit through the brain. Cross inhibition of the unidirectional movement of glycine was not demonstrable. These present results and most previous studies suggest that this putative neurotransmitter does not cross the blood-brain barrier by a carrier mediated process.", "contents": "Movement of glycine across the blood-brain barrier of the rabbit. The single pass clearance of glycine from the cerebral capillary bed was measured in the rabbit with the indicator diffusion method. It was shown that glycine was extracted to the same degree as fructose (ca..07). The concentration of glycine injected into the carotid artery was varied some 700-fold without significantly affecting the clearance of this amino acid in transit through the brain. Cross inhibition of the unidirectional movement of glycine was not demonstrable. These present results and most previous studies suggest that this putative neurotransmitter does not cross the blood-brain barrier by a carrier mediated process."} {"id": "PMID:1262869", "title": "Electrophysiological study of corticocaudate projections in cats.", "content": "The potential waves evoked in the caudate nucleus (CN) of cats by stimulation of the cerebral neocortex were sterotactically recorded. The head and the body of the caudate nucleus were systematically explored. Stimulation of the ipsilateral sigmoid gyrus and the orbitofrontal cortex evoked waves with the largest amplitude in the CN. Smaller potentials were evoked from the ipsilateral ectosylvian and suprasylvian gyri and from the sigmoid gyrus on the contralateral side. Antidromic conduction from the caudate nucleus to the cortex demonstrated the directness of the corticocaudate pathway. By stimulating the white matter and by amking lesions, the corticocaudate pathway was shown to pass, in part, through the subcallosal fasciculus and, in part, through the internal capsule. Corticocaudate connections were shown to be separate from the fibers of the corticospinal tract. A staggered and extensively overlapping topographic progression of the corticocaudate projections was demonstrable along the antero-posterior axis, but was less evident in the medio-lateral direction. It was concluded that the intranuclear distribution of functional synaptic connections must be more profusely branched than was suspected from anatomical data.", "contents": "Electrophysiological study of corticocaudate projections in cats. The potential waves evoked in the caudate nucleus (CN) of cats by stimulation of the cerebral neocortex were sterotactically recorded. The head and the body of the caudate nucleus were systematically explored. Stimulation of the ipsilateral sigmoid gyrus and the orbitofrontal cortex evoked waves with the largest amplitude in the CN. Smaller potentials were evoked from the ipsilateral ectosylvian and suprasylvian gyri and from the sigmoid gyrus on the contralateral side. Antidromic conduction from the caudate nucleus to the cortex demonstrated the directness of the corticocaudate pathway. By stimulating the white matter and by amking lesions, the corticocaudate pathway was shown to pass, in part, through the subcallosal fasciculus and, in part, through the internal capsule. Corticocaudate connections were shown to be separate from the fibers of the corticospinal tract. A staggered and extensively overlapping topographic progression of the corticocaudate projections was demonstrable along the antero-posterior axis, but was less evident in the medio-lateral direction. It was concluded that the intranuclear distribution of functional synaptic connections must be more profusely branched than was suspected from anatomical data."} {"id": "PMID:1262887", "title": "Observations on sensory and sympathetic function during intrathecal analgesia.", "content": "A dilute solution of procaine in glucose solution was injected by slow drip into the lumbar theca of patients to cause a differential block. Vasodilatation of the skin vessels of the lower limbs always occurred before any change in sensibility. The first changes in sensibility were inability to fell painful stimuli and warm stimuli; these two forms of sensibility were usually coextensive and occurred at the same time. When this was not so, either form of sensibility could be more extensively disturbed than the other. When warmth sensibility was removed, cold sensibility was either normal or diminished or cold stimuli caused non-thermal sensations such as non-thermal wetness or pressure. It is concluded that the nerve fibres signalling warmth are the smaller delta fibres or non-myelinated fibres or both. As two groups of investigators who recorded from the non-myelinated fibres in man found no non-myelinated fibres responding to cold, it is condluded that fibres signalling cold cover the same delta range as those signalling warmth, together with a proportion of larger delta fibres. When fibres subserving pain, warmth, and cold were blocked, tactile sensibility could be normal. It is concluded that, if there are tactile fibres in man in the smaller delta and non-myelinated ranges, their contribution to tactile sensibility is insignificant. It is also concluded that the pre-galglionic B fibres are the most susceptible of all fibres of the nerve roots to local anaesthetic agents. On two occasions, piloerection occurred when the pre-ganglionic sympathetic fibres were blocked. In two patients spontaneous itching occurred when all peripheral nerve fibres were blocked except large tactile fibres.", "contents": "Observations on sensory and sympathetic function during intrathecal analgesia. A dilute solution of procaine in glucose solution was injected by slow drip into the lumbar theca of patients to cause a differential block. Vasodilatation of the skin vessels of the lower limbs always occurred before any change in sensibility. The first changes in sensibility were inability to fell painful stimuli and warm stimuli; these two forms of sensibility were usually coextensive and occurred at the same time. When this was not so, either form of sensibility could be more extensively disturbed than the other. When warmth sensibility was removed, cold sensibility was either normal or diminished or cold stimuli caused non-thermal sensations such as non-thermal wetness or pressure. It is concluded that the nerve fibres signalling warmth are the smaller delta fibres or non-myelinated fibres or both. As two groups of investigators who recorded from the non-myelinated fibres in man found no non-myelinated fibres responding to cold, it is condluded that fibres signalling cold cover the same delta range as those signalling warmth, together with a proportion of larger delta fibres. When fibres subserving pain, warmth, and cold were blocked, tactile sensibility could be normal. It is concluded that, if there are tactile fibres in man in the smaller delta and non-myelinated ranges, their contribution to tactile sensibility is insignificant. It is also concluded that the pre-galglionic B fibres are the most susceptible of all fibres of the nerve roots to local anaesthetic agents. On two occasions, piloerection occurred when the pre-ganglionic sympathetic fibres were blocked. In two patients spontaneous itching occurred when all peripheral nerve fibres were blocked except large tactile fibres."} {"id": "PMID:1262888", "title": "Vertebrobasilar artery insufficiency in rheumatoid atlantoaxial subluxation.", "content": "Cervical myelopathy has become commonly recognized as a complication of rheumatoid atlantoaxial subluxation. A small group of patients with atlantoaxial subluxation may have intermittent symptoms associated with change of head position and which are due to vertebral artery compression. Two such cases are reported, one with necropsy findings of infarction in the area supplied by the vertebrobasilar system. The pathogenesis of the symptomatology and infarction is discussed.", "contents": "Vertebrobasilar artery insufficiency in rheumatoid atlantoaxial subluxation. Cervical myelopathy has become commonly recognized as a complication of rheumatoid atlantoaxial subluxation. A small group of patients with atlantoaxial subluxation may have intermittent symptoms associated with change of head position and which are due to vertebral artery compression. Two such cases are reported, one with necropsy findings of infarction in the area supplied by the vertebrobasilar system. The pathogenesis of the symptomatology and infarction is discussed."} {"id": "PMID:1262889", "title": "Measurement of regional cerebral blood volume by computerized axial tomography.", "content": "Computerized tomography has been used for the estimation of regional cerebral blood volume in a group of 18 patients. Sodium iothalamate was injected intravenously (1.75 ml/kg) to increase the absorption of x-rays in the cerebral circulation. A mean value of 5.7 ml/100 g was found for the cortex and 5.1 for tha thalamus.", "contents": "Measurement of regional cerebral blood volume by computerized axial tomography. Computerized tomography has been used for the estimation of regional cerebral blood volume in a group of 18 patients. Sodium iothalamate was injected intravenously (1.75 ml/kg) to increase the absorption of x-rays in the cerebral circulation. A mean value of 5.7 ml/100 g was found for the cortex and 5.1 for tha thalamus."} {"id": "PMID:1262890", "title": "Muscle nuclear size in neuromuscular disease.", "content": "Nuclear size has been estimated in muscle biopsy specimens from seven healthy individuals, eight patients with infantile spinal muscular atrophy (types I and II), and eight patients with Duchenne muscular dystrophy. The results indicate a great increase in nuclear size in Duchenne muscular dystrophy but not in spinal muscular atrophy when compared with controls. The reasons for this finding are discussed in relation to the pathogenesis of these two groups of diseases.", "contents": "Muscle nuclear size in neuromuscular disease. Nuclear size has been estimated in muscle biopsy specimens from seven healthy individuals, eight patients with infantile spinal muscular atrophy (types I and II), and eight patients with Duchenne muscular dystrophy. The results indicate a great increase in nuclear size in Duchenne muscular dystrophy but not in spinal muscular atrophy when compared with controls. The reasons for this finding are discussed in relation to the pathogenesis of these two groups of diseases."} {"id": "PMID:1262891", "title": "Prognostic significance of electrodiagnostic studies in the Guillain-Barr\u00e9 syndrome.", "content": "Nerve conduction and needle electromyographic studies were carried out in 50 patients with the Landry-Guillain-Barr\u00e9 syndrome to assess the reliability of this procedure in predicting the prognosis. Two main groups were identified. The first group was characterized by gross abnormalities in nerve conduction and absence of fibrillation potentials during the entire course of the illness. Twenty-five of 31 patients (80.6%) belonging to this group recovered rapidly, and the quality of recovery was good. In 19 patients belonging to the second group, profuse fibrillations were noted within the first four weeks of the illness with or without associated nerve conduction deficits. Recovery in this group was poor (31.5%) and pronounced residual deficits were more common. Electrophysiological studies therefore are of value not only in the diagnosis but also as a reliable prognostic index in this syndrome.", "contents": "Prognostic significance of electrodiagnostic studies in the Guillain-Barr\u00e9 syndrome. Nerve conduction and needle electromyographic studies were carried out in 50 patients with the Landry-Guillain-Barr\u00e9 syndrome to assess the reliability of this procedure in predicting the prognosis. Two main groups were identified. The first group was characterized by gross abnormalities in nerve conduction and absence of fibrillation potentials during the entire course of the illness. Twenty-five of 31 patients (80.6%) belonging to this group recovered rapidly, and the quality of recovery was good. In 19 patients belonging to the second group, profuse fibrillations were noted within the first four weeks of the illness with or without associated nerve conduction deficits. Recovery in this group was poor (31.5%) and pronounced residual deficits were more common. Electrophysiological studies therefore are of value not only in the diagnosis but also as a reliable prognostic index in this syndrome."} {"id": "PMID:1262892", "title": "Central effect of bladder filling and voiding.", "content": "In normal subjects and in patients with spasticity and/or urological complaints changes in somatic muscle reflexes associated with filling of the urinary bladder were observed. Two different patterns of reflex changes occurred. One pattern was associated with easy initiation of voiding: it consisted of increasing H and T reflexes and decreasing flexor reflexes with concomitant decreasing sphincter muscle activity. The other pattern was associated with difficulty in initiation of voiding: it consisted of increasing flexor relfexes including sphincter muscle activity and decreasing H and T reflexes. The importance of these reflex patterns in disturbances of micturition is discussed. During voiding, decreasing flexor relfexes with increasing H and T reflexes occur as the general pattern.", "contents": "Central effect of bladder filling and voiding. In normal subjects and in patients with spasticity and/or urological complaints changes in somatic muscle reflexes associated with filling of the urinary bladder were observed. Two different patterns of reflex changes occurred. One pattern was associated with easy initiation of voiding: it consisted of increasing H and T reflexes and decreasing flexor reflexes with concomitant decreasing sphincter muscle activity. The other pattern was associated with difficulty in initiation of voiding: it consisted of increasing flexor relfexes including sphincter muscle activity and decreasing H and T reflexes. The importance of these reflex patterns in disturbances of micturition is discussed. During voiding, decreasing flexor relfexes with increasing H and T reflexes occur as the general pattern."} {"id": "PMID:1262893", "title": "Baroreflex sensitivity and responses to the Valsalva manoeuvre in subjects with diabetes mellitus.", "content": "Baroreflex sensitivity was measured in a group of diabetic patients from the slope of the regression of pulse interval on systolic arterial pressure, during elevation of pressure induced by phenylephrine. The response to Valsalva's manoeuvre was assessed in the same subjects. There was a good correlation between the two tests in the identification of patients with a parasympathetic autonomic disturbance, but measurements of baroreflex sensitivity were more readily quantifiable than were the responses to Valsalva's manoeuvre. Furthermore, baroreflex sensitivity could be measured in patients with sympathetic nervous dysfunction in whom vagal function could not be assessed by means of the Valsalva manoeuvre. Measurement of baroreflex sensitivity is likely to be suitable for longitudinal studies of the progress of diabetic autonomic neuropathy.", "contents": "Baroreflex sensitivity and responses to the Valsalva manoeuvre in subjects with diabetes mellitus. Baroreflex sensitivity was measured in a group of diabetic patients from the slope of the regression of pulse interval on systolic arterial pressure, during elevation of pressure induced by phenylephrine. The response to Valsalva's manoeuvre was assessed in the same subjects. There was a good correlation between the two tests in the identification of patients with a parasympathetic autonomic disturbance, but measurements of baroreflex sensitivity were more readily quantifiable than were the responses to Valsalva's manoeuvre. Furthermore, baroreflex sensitivity could be measured in patients with sympathetic nervous dysfunction in whom vagal function could not be assessed by means of the Valsalva manoeuvre. Measurement of baroreflex sensitivity is likely to be suitable for longitudinal studies of the progress of diabetic autonomic neuropathy."} {"id": "PMID:1262894", "title": "Stroke associated with addiction to heroin.", "content": "During a five year period at the Harlem Hospital Center nine heroin addicts were seen with strokes. Four occurred after loss of consciousness following intravenous heroin. Two occurred in patients using heroin at the time, but were not related to overdose or to a particular recent injection. The youth of these patients and lack of other predisposing factors suggests that heroin played a role in their strokes. In the other three patients, the relationships of stroke to heroin is less persuasive. There are several possible mechanisms by which heroin abuse could lead to stroke.", "contents": "Stroke associated with addiction to heroin. During a five year period at the Harlem Hospital Center nine heroin addicts were seen with strokes. Four occurred after loss of consciousness following intravenous heroin. Two occurred in patients using heroin at the time, but were not related to overdose or to a particular recent injection. The youth of these patients and lack of other predisposing factors suggests that heroin played a role in their strokes. In the other three patients, the relationships of stroke to heroin is less persuasive. There are several possible mechanisms by which heroin abuse could lead to stroke."} {"id": "PMID:1262896", "title": "The normal motor unit in man. A single fibre EMG multielectrode investigation.", "content": "The motor unit in the normal EDC and biceps brachii muscle was studied with a multielectrode technique permitting recording from 44 sites 300 mum apart. It was found that the muscle fibres in man are scattered with no evidence of grouping, similar to the findings in glycogen depletion experiments in animals.", "contents": "The normal motor unit in man. A single fibre EMG multielectrode investigation. The motor unit in the normal EDC and biceps brachii muscle was studied with a multielectrode technique permitting recording from 44 sites 300 mum apart. It was found that the muscle fibres in man are scattered with no evidence of grouping, similar to the findings in glycogen depletion experiments in animals."} {"id": "PMID:1262897", "title": "Eales' disease with neurological involvement. Part 2. Pathology and pathogenesis.", "content": "Detailed neuropathologic examination was carried out on 1 case of Eales' disease with CNS involvement, in the form of retinal vasculopathy, followed first by signs of brain stem and cerebellar disease and then by a myelopathy, with death 4 years later from retinal infection. There was mild chronic inflammation in the retina, and sub-total demyelination of one optic nerve. The brain stem and cerebellum showed extensive vasculopathy, with various stages of venous change extending from proliferation and dilatation to haemorrhage, or to thickening with hyalinisation. The perivenular brain tissue, particularly of the cerebellum, often showed demyelination, with relative axon preservation, but no inflammation. Similar, but less pronounced venopathy was seen in the dorsal cord. There was ascending degeneration of Goll's columns and descending degeneration of the lateral columns.", "contents": "Eales' disease with neurological involvement. Part 2. Pathology and pathogenesis. Detailed neuropathologic examination was carried out on 1 case of Eales' disease with CNS involvement, in the form of retinal vasculopathy, followed first by signs of brain stem and cerebellar disease and then by a myelopathy, with death 4 years later from retinal infection. There was mild chronic inflammation in the retina, and sub-total demyelination of one optic nerve. The brain stem and cerebellum showed extensive vasculopathy, with various stages of venous change extending from proliferation and dilatation to haemorrhage, or to thickening with hyalinisation. The perivenular brain tissue, particularly of the cerebellum, often showed demyelination, with relative axon preservation, but no inflammation. Similar, but less pronounced venopathy was seen in the dorsal cord. There was ascending degeneration of Goll's columns and descending degeneration of the lateral columns."} {"id": "PMID:1262898", "title": "Glycine levels in the degenerated human spinal cord.", "content": "Tissues from non-degenerated tissue of 18 patients were assayed for glycine concentration in grey and white matter in the thoracic, cervical and lumbar regions. Confirming earlier results, glycine concentration was found to be maximal in the grey matter of the lumbar segments of the lateral column. Analysis of tissue from 11 human spinal cords showing unilateral Wallerian degeneration, 4 cords with amyotrophic sclerosis and 4 cords with bilateral Wallerian degeneration failed to show statistically significant differences when compared with control values. The results argue against a supraspinal origin of glycine and suggest that glycine levels are regulated locally or at a segmental level in the spinal cord in man.", "contents": "Glycine levels in the degenerated human spinal cord. Tissues from non-degenerated tissue of 18 patients were assayed for glycine concentration in grey and white matter in the thoracic, cervical and lumbar regions. Confirming earlier results, glycine concentration was found to be maximal in the grey matter of the lumbar segments of the lateral column. Analysis of tissue from 11 human spinal cords showing unilateral Wallerian degeneration, 4 cords with amyotrophic sclerosis and 4 cords with bilateral Wallerian degeneration failed to show statistically significant differences when compared with control values. The results argue against a supraspinal origin of glycine and suggest that glycine levels are regulated locally or at a segmental level in the spinal cord in man."} {"id": "PMID:1262899", "title": "Testosterone-induced changes of choline acetyl-transferase and cholinesterase activities in rat levator ani muscle.", "content": "One year after castration the activities of choline acetyltransferase (ChAc) and of cholinesterase (ChE) in the levator ani (LA) muscle of male rats were lowered by 42 and 79% respectively. The weight of the muscle corresponded to 15% of control values. These changes were not accompanied by a decrease in the number of the muscle fibres. Treatment with testosterone rapidly increased the activity of ChAc and the weight of the muscle near to control values; the restoration of ChE was less complete. Testosterone produced an increase in the size of the muscle fibres and increased the histochemically observed activity of ChE in the postsynaptic part of the motor end-plates. In non-castrated rats the administration of testosterone increased the weight ofthe LA muscle, but was not accompanied by an increase of ChAc above control values.", "contents": "Testosterone-induced changes of choline acetyl-transferase and cholinesterase activities in rat levator ani muscle. One year after castration the activities of choline acetyltransferase (ChAc) and of cholinesterase (ChE) in the levator ani (LA) muscle of male rats were lowered by 42 and 79% respectively. The weight of the muscle corresponded to 15% of control values. These changes were not accompanied by a decrease in the number of the muscle fibres. Treatment with testosterone rapidly increased the activity of ChAc and the weight of the muscle near to control values; the restoration of ChE was less complete. Testosterone produced an increase in the size of the muscle fibres and increased the histochemically observed activity of ChE in the postsynaptic part of the motor end-plates. In non-castrated rats the administration of testosterone increased the weight ofthe LA muscle, but was not accompanied by an increase of ChAc above control values."} {"id": "PMID:1262900", "title": "Effects of castration, testosterone and immobilization on the activities of choline acetyltransferase and cholinesterase in rat limb muscles.", "content": "Thirteen months after castration of male rats the weight of their soleus muscles was lowered to 82% and their choline acetyltransferase (ChAc) activity to 83% of control values. The administration of testosterone lasting 5 weeks increased the weight of the soleus muscles of castrated animals by 19% and their ChAc activity bu 37%. Changes in the activity of cholinesterase occurring after castration and testosterone treatment were not statistically significant. It is assumed taht the effect of testosterone on the activity of ChAc was mainly due to an increase in the functional activity of the motoneurones innervating the muscle. Rapid developmental increase of ChAc activity was observed in the muscles of intact rats between the age of 48 and 82 days. During this period of development the activity of ChAc rose faster than the weight of the muscles. Testosterone had no effect on the weight and ChAc activity of the soleus and extensor digitorum longus muscles of non-castrated rats after 1 week's administration; after 5 weeks' administration the weight of the muscles and their ChAc activity were diminished. After the soleus muscles of non-castrated rats had been immobilized for 10 days, their ChAc activity was 56% and their weight 51% of control values. The administration of testosterone did not alter the effect of immobilization on the ChAc and weight of the muscle.", "contents": "Effects of castration, testosterone and immobilization on the activities of choline acetyltransferase and cholinesterase in rat limb muscles. Thirteen months after castration of male rats the weight of their soleus muscles was lowered to 82% and their choline acetyltransferase (ChAc) activity to 83% of control values. The administration of testosterone lasting 5 weeks increased the weight of the soleus muscles of castrated animals by 19% and their ChAc activity bu 37%. Changes in the activity of cholinesterase occurring after castration and testosterone treatment were not statistically significant. It is assumed taht the effect of testosterone on the activity of ChAc was mainly due to an increase in the functional activity of the motoneurones innervating the muscle. Rapid developmental increase of ChAc activity was observed in the muscles of intact rats between the age of 48 and 82 days. During this period of development the activity of ChAc rose faster than the weight of the muscles. Testosterone had no effect on the weight and ChAc activity of the soleus and extensor digitorum longus muscles of non-castrated rats after 1 week's administration; after 5 weeks' administration the weight of the muscles and their ChAc activity were diminished. After the soleus muscles of non-castrated rats had been immobilized for 10 days, their ChAc activity was 56% and their weight 51% of control values. The administration of testosterone did not alter the effect of immobilization on the ChAc and weight of the muscle."} {"id": "PMID:1262901", "title": "The metabolic and hormonal response to glucagon. Part 1. Normal subjects.", "content": "Significant increases in mean plasma noradrenaline levels were observed 30-60 min and 150-180 min after a subcutaneous injection of 1 mg glucagon. The first peak coincided with the maximum blood glucose and plasma insulin levels and the second peak occurred after plasma growth hormone (GH) and cortisol levels had begun to rise. The first plasma noradrenaline peak may be important in inhibiting further insulin secretion. There was no evidence that glucagon stimulates adrenaline secretion in normal human subjects. It was also confirmed that there are significant increases in the levels of glucose, insulin, GH and cortisol and a significant decrease in FFA levels following subcutaneous injection of glucagon in normal human subjects.", "contents": "The metabolic and hormonal response to glucagon. Part 1. Normal subjects. Significant increases in mean plasma noradrenaline levels were observed 30-60 min and 150-180 min after a subcutaneous injection of 1 mg glucagon. The first peak coincided with the maximum blood glucose and plasma insulin levels and the second peak occurred after plasma growth hormone (GH) and cortisol levels had begun to rise. The first plasma noradrenaline peak may be important in inhibiting further insulin secretion. There was no evidence that glucagon stimulates adrenaline secretion in normal human subjects. It was also confirmed that there are significant increases in the levels of glucose, insulin, GH and cortisol and a significant decrease in FFA levels following subcutaneous injection of glucagon in normal human subjects."} {"id": "PMID:1262902", "title": "The metabolic and hormonal response to glucagon. Part 2. In patients with migraine.", "content": "The hormonal and metabolic changes following the subcutaneous injection of 1 mg glucagon have been studied in a group of 6 migraine patients, and the results indicate that the responses of these subjects differ from those of a control group. Three of the migraine subjects had raised basal plasma noradrenaline levels but all had been taking clonidine up to 12-24 hr before the test and the increased plasma noradrenaline levels were probably due to the effect of withdrawal of the drug.", "contents": "The metabolic and hormonal response to glucagon. Part 2. In patients with migraine. The hormonal and metabolic changes following the subcutaneous injection of 1 mg glucagon have been studied in a group of 6 migraine patients, and the results indicate that the responses of these subjects differ from those of a control group. Three of the migraine subjects had raised basal plasma noradrenaline levels but all had been taking clonidine up to 12-24 hr before the test and the increased plasma noradrenaline levels were probably due to the effect of withdrawal of the drug."} {"id": "PMID:1262903", "title": "Senile changes in the human neocortex and hippocampus compared by the use of the electron and light microscopes.", "content": "The severity of certain \"senile\" changes, namely senile plaques, neurofibrillary tangles and granulovacuolar degeneration in the neocortex and hippocampus, was estimated by light microscopy, in brains obtained at autopsy from 16 cases aged 24 to 93 years. An assessment of certain features of plaques and tangles as well as Hirano-bodies (also associated with senile change) was made by electron microscopy. A statistically significant correlation was found between the electron-microscopic and light-microscopic findings. The findings in an additional 4 cases aged 39 to 65 years in which only the cortex was examined supported the correlation.", "contents": "Senile changes in the human neocortex and hippocampus compared by the use of the electron and light microscopes. The severity of certain \"senile\" changes, namely senile plaques, neurofibrillary tangles and granulovacuolar degeneration in the neocortex and hippocampus, was estimated by light microscopy, in brains obtained at autopsy from 16 cases aged 24 to 93 years. An assessment of certain features of plaques and tangles as well as Hirano-bodies (also associated with senile change) was made by electron microscopy. A statistically significant correlation was found between the electron-microscopic and light-microscopic findings. The findings in an additional 4 cases aged 39 to 65 years in which only the cortex was examined supported the correlation."} {"id": "PMID:1262904", "title": "Chronic relapsing polyneuritis.", "content": "Clinical, electrophysiological and pathological findings in 23 patients with subacute and relapsing idiopathic demyelinating polyneuropathies are described. In 17 patients with relapsing polyneuropathy, the neurological illness was unaccompanied by any systemic disturbances. The term preferred for the neuropathy in this group of patients is chronic relapsing polyneuritis. The findings in this group suggest that the common form of this syndrome is due to a single disease entity. Chronic relapsing polyneuritis differs from acute idiopathic polyneuritis chiefly in regard to the rate of evolution and the severity of the initial episode of polyneuropathy. If these two polyneuropathies have the same pathogenesis, the factor which determines whether the disease is acute and self-limiting or chronically relapsing is often present at the time of onset of the disease. The relationship of chronic relapsing polyneuritis to relapsing hypertrophic polyneuropathy and progressive hypertrophic polyneuropathy is also discussed and it is concluded that these diseases may constitute a spectrum of pathogenetically related disorders. In chronic relapsing polyneuritis, as in other demyelinating polyneuropathies, a marked segmental reduction in axon diameter accompanies demyelination. This corresponds to a more than 50% reduction in the volume of the affected region of the axon and it is associated with increased packing of axoplasmic organelles and wrinkling of the axolemma. It is suggested that in the normal myelinated nerve fibre, the Schwann cell and myelin sheath maintain fluid locally within the axon.", "contents": "Chronic relapsing polyneuritis. Clinical, electrophysiological and pathological findings in 23 patients with subacute and relapsing idiopathic demyelinating polyneuropathies are described. In 17 patients with relapsing polyneuropathy, the neurological illness was unaccompanied by any systemic disturbances. The term preferred for the neuropathy in this group of patients is chronic relapsing polyneuritis. The findings in this group suggest that the common form of this syndrome is due to a single disease entity. Chronic relapsing polyneuritis differs from acute idiopathic polyneuritis chiefly in regard to the rate of evolution and the severity of the initial episode of polyneuropathy. If these two polyneuropathies have the same pathogenesis, the factor which determines whether the disease is acute and self-limiting or chronically relapsing is often present at the time of onset of the disease. The relationship of chronic relapsing polyneuritis to relapsing hypertrophic polyneuropathy and progressive hypertrophic polyneuropathy is also discussed and it is concluded that these diseases may constitute a spectrum of pathogenetically related disorders. In chronic relapsing polyneuritis, as in other demyelinating polyneuropathies, a marked segmental reduction in axon diameter accompanies demyelination. This corresponds to a more than 50% reduction in the volume of the affected region of the axon and it is associated with increased packing of axoplasmic organelles and wrinkling of the axolemma. It is suggested that in the normal myelinated nerve fibre, the Schwann cell and myelin sheath maintain fluid locally within the axon."} {"id": "PMID:1262905", "title": "Multiple sclerosis amongst Chinese in Taiwan.", "content": "Twenty-five cases of multiple sclerosis (MS), including 2 autopsy cases, collected during the past 20 years from amongst the Chinese of Taiwan, are reported. These cases fulfilled all the clinical diagnostic criteria of MS. The following observations were made: (1) Multiple sclerosis does exist among Chinese in Taiwan. It is uncommon, but is by no means a very rare disease. The prevalence rate in northern Taiwan near Taipei is estimated as 0.8/100.000 population. (2) Female preponderence was conspicuous (F:M = 3.2.:1) in our MS cases as well as in other demyelinating diseases. (3) On the whole, the onset of the disease was earlier in female patients, and those who had their initial symptoms before the age of 20 years were all females. (4) The optic nerve was most frequently involved at the onset, and it was involved in the majority of patients during the whole clinical course. (5) Involvement of the optic nerve and spinal cord, with or without the brain stem, was the commonest form of our MS cases, especially among female patients. (6) More malignant forms of MS, with acute onset and rapid clinical course leading to severe incapacity or fatality, were more common among female patients. (7) Painful tonic spasms were relatively frequently encountered, and they were usually seen in patients with severe spinal cord involvement. (8) Marked elevation of the CSF total protein and of leukocytes was relatively frequent during severe relapses in patients with spinal cord lesions. (9) Severe and extensive demyelinating lesions, both old and recent, in the optic nerve and spinal cord were seen in 2 autopsy cases. The relationship between MS and NMO in Oriental patients is briefly discussed. (10) It seems likely that cases of MS which are atypical as compared with Western MS are more frequently seen in Oriental countries, and perhaps also in tropical regions where MS is known to be rare.", "contents": "Multiple sclerosis amongst Chinese in Taiwan. Twenty-five cases of multiple sclerosis (MS), including 2 autopsy cases, collected during the past 20 years from amongst the Chinese of Taiwan, are reported. These cases fulfilled all the clinical diagnostic criteria of MS. The following observations were made: (1) Multiple sclerosis does exist among Chinese in Taiwan. It is uncommon, but is by no means a very rare disease. The prevalence rate in northern Taiwan near Taipei is estimated as 0.8/100.000 population. (2) Female preponderence was conspicuous (F:M = 3.2.:1) in our MS cases as well as in other demyelinating diseases. (3) On the whole, the onset of the disease was earlier in female patients, and those who had their initial symptoms before the age of 20 years were all females. (4) The optic nerve was most frequently involved at the onset, and it was involved in the majority of patients during the whole clinical course. (5) Involvement of the optic nerve and spinal cord, with or without the brain stem, was the commonest form of our MS cases, especially among female patients. (6) More malignant forms of MS, with acute onset and rapid clinical course leading to severe incapacity or fatality, were more common among female patients. (7) Painful tonic spasms were relatively frequently encountered, and they were usually seen in patients with severe spinal cord involvement. (8) Marked elevation of the CSF total protein and of leukocytes was relatively frequent during severe relapses in patients with spinal cord lesions. (9) Severe and extensive demyelinating lesions, both old and recent, in the optic nerve and spinal cord were seen in 2 autopsy cases. The relationship between MS and NMO in Oriental patients is briefly discussed. (10) It seems likely that cases of MS which are atypical as compared with Western MS are more frequently seen in Oriental countries, and perhaps also in tropical regions where MS is known to be rare."} {"id": "PMID:1262906", "title": "A mathematical model of cerebrospinal fluid dynamics.", "content": "The ability to solve systems of simultaneous non-linear differential equations by a combination of analytical and computational techniques has encouraged the development of valid mathematical models of biological phenomena. The dynamics of the cerebrospinal fluid (CSF) system has been the subject of closer scrutiny in recent years since the recognition of symptomatic low-pressure hydrocephalic states in man. A mathematical model has been derived from 7 assumptions: (1) That the brain is a spherical shell. (2) That CSF is secreted at a constant rate. (3) That CSF absorption is linearly dependent on pressure. (4) That flow between the CSF compartments is proportional to the pressure difference. (5) That Laplace's Law holds for the visco-elastic properties of the brain. (6) That there is compliance in the spinal compartment of the CSF system. (7) That vascular pulsations in the cranial and spinal compartments are capacitatively coupled. Using known data (and estimates of as yet unknown values) for the several parameters, the validity of the model has been successfully tested against 3 clinical conditions. This model extends our understanding of derangements of CSF dynamics and suggest where further research may yield data at present lacking.", "contents": "A mathematical model of cerebrospinal fluid dynamics. The ability to solve systems of simultaneous non-linear differential equations by a combination of analytical and computational techniques has encouraged the development of valid mathematical models of biological phenomena. The dynamics of the cerebrospinal fluid (CSF) system has been the subject of closer scrutiny in recent years since the recognition of symptomatic low-pressure hydrocephalic states in man. A mathematical model has been derived from 7 assumptions: (1) That the brain is a spherical shell. (2) That CSF is secreted at a constant rate. (3) That CSF absorption is linearly dependent on pressure. (4) That flow between the CSF compartments is proportional to the pressure difference. (5) That Laplace's Law holds for the visco-elastic properties of the brain. (6) That there is compliance in the spinal compartment of the CSF system. (7) That vascular pulsations in the cranial and spinal compartments are capacitatively coupled. Using known data (and estimates of as yet unknown values) for the several parameters, the validity of the model has been successfully tested against 3 clinical conditions. This model extends our understanding of derangements of CSF dynamics and suggest where further research may yield data at present lacking."} {"id": "PMID:1262907", "title": "[Proliferation of the transverse tubular system during a tardive and familial myopathy].", "content": "The authors report a case of non-progressive, late-onset, recessive, sex-linked myopathy. Electron microscopy reveals a striking proliferation of the T system. This proliferation might be interpreted as indicating an abortive attempt of muscle to regenerate, which could explain the clinical course. Some basic ultrastructural aspects concerning the T system are reported. The signification of the findings of numerous \"zebra bodies\" is discussed.", "contents": "[Proliferation of the transverse tubular system during a tardive and familial myopathy]. The authors report a case of non-progressive, late-onset, recessive, sex-linked myopathy. Electron microscopy reveals a striking proliferation of the T system. This proliferation might be interpreted as indicating an abortive attempt of muscle to regenerate, which could explain the clinical course. Some basic ultrastructural aspects concerning the T system are reported. The signification of the findings of numerous \"zebra bodies\" is discussed."} {"id": "PMID:1262908", "title": "Undernutrition and the developing cerebellar cortex in the rat.", "content": "Undernutrition of the newborn rats, produced during the first 3 weeks by increasing the litter size and restricting the mother's diet, resulted in reduction of the body and brain weights of the experimental animals. One group of undernourished animals showed especially severe reduction of body and cerebellar weights. These animals, on the 10th postnatal day, had an immature cerebellar cortex corresponding to that of the 7th day postnatal control animals. The external granular layer persisted in the cerebellar cortex of the underweight animals until the 23rd day, while it disappeared by 20th day in the control animals. Mitotic activity was evident until the 21st postnatal day in these animals while it stopped in the normal animal by 16th postnatal day. There was no marked difference in the fine structure of the various cell types in the control and undernourished animals. Midsagittal tracings of the cerebellar cortex showed a reduced surface area in the undernourished animals, while the thickness of the external granular layer and molecular layer did not show any significant difference when compared to that of the control animals, thus showing a reduction in total cell number, but not per unit area. The normal morphological appearance of the cerebellar cortex in the underfed animals of higher weight probably indicates that these animals are adequately nourished in spite of the reduction in weight when compared to the control animals, which probably are overfed.", "contents": "Undernutrition and the developing cerebellar cortex in the rat. Undernutrition of the newborn rats, produced during the first 3 weeks by increasing the litter size and restricting the mother's diet, resulted in reduction of the body and brain weights of the experimental animals. One group of undernourished animals showed especially severe reduction of body and cerebellar weights. These animals, on the 10th postnatal day, had an immature cerebellar cortex corresponding to that of the 7th day postnatal control animals. The external granular layer persisted in the cerebellar cortex of the underweight animals until the 23rd day, while it disappeared by 20th day in the control animals. Mitotic activity was evident until the 21st postnatal day in these animals while it stopped in the normal animal by 16th postnatal day. There was no marked difference in the fine structure of the various cell types in the control and undernourished animals. Midsagittal tracings of the cerebellar cortex showed a reduced surface area in the undernourished animals, while the thickness of the external granular layer and molecular layer did not show any significant difference when compared to that of the control animals, thus showing a reduction in total cell number, but not per unit area. The normal morphological appearance of the cerebellar cortex in the underfed animals of higher weight probably indicates that these animals are adequately nourished in spite of the reduction in weight when compared to the control animals, which probably are overfed."} {"id": "PMID:1262909", "title": "Three dimensional analysis of unmyelinated fibers in normal and pathologic autonomic nerves.", "content": "The technique of serial-section electron microscopy and diagrammatic three dimensional reconstructions has been used to assess normal and pathological unmyelinated nerve fibers from a peripheral autonomic nerve: the rat cervical sympathetic trunk. Within this predominantly unmyelinated nerve, there is a complex arrangement of axons into longitudinally oriented bundles brought together by chains of Schwann cells. Each bundle is subdivided into smaller components by the cytoplasmic processes of Schwann cells; such subdivisions, which are basal lamina-enclosed masses of Schwann cell cytoplasm, when viewed on cross-sectional electron micrographs, are termed Schwann cell units. The size and shape of each Schwann cell unit varies along the length of fibres, but the diameter of individual axons shows little variation over the segments studied. Axonal branching was not observed in normal unmyelinated nerves. Crush injury and x-irradiation produces different patterns of alteration in the axon-Schwann cell relationships of unmyelinated nerves. Following crush injury, Schwann cell processes increase in diameter and contain numerous small diameter axonal sprouts. Many of the regenerating axons remain thin while others reacquire a normal diameter. X-irradiation affects Schwann cells leading to retraction of their processes and the appearance of naked axonal segments.", "contents": "Three dimensional analysis of unmyelinated fibers in normal and pathologic autonomic nerves. The technique of serial-section electron microscopy and diagrammatic three dimensional reconstructions has been used to assess normal and pathological unmyelinated nerve fibers from a peripheral autonomic nerve: the rat cervical sympathetic trunk. Within this predominantly unmyelinated nerve, there is a complex arrangement of axons into longitudinally oriented bundles brought together by chains of Schwann cells. Each bundle is subdivided into smaller components by the cytoplasmic processes of Schwann cells; such subdivisions, which are basal lamina-enclosed masses of Schwann cell cytoplasm, when viewed on cross-sectional electron micrographs, are termed Schwann cell units. The size and shape of each Schwann cell unit varies along the length of fibres, but the diameter of individual axons shows little variation over the segments studied. Axonal branching was not observed in normal unmyelinated nerves. Crush injury and x-irradiation produces different patterns of alteration in the axon-Schwann cell relationships of unmyelinated nerves. Following crush injury, Schwann cell processes increase in diameter and contain numerous small diameter axonal sprouts. Many of the regenerating axons remain thin while others reacquire a normal diameter. X-irradiation affects Schwann cells leading to retraction of their processes and the appearance of naked axonal segments."} {"id": "PMID:1262910", "title": "Membranous bodies in the cerebral cortex of aging rats: an electron microscope study.", "content": "Large complex membranous bodies are described in the cerebral cortex of adult rats. Although these bodies are not very prevalent, they appear with increasing frequency as the age of the animal increases from 12 to 28 months. The membranous bodies are composed of varying amounts of membranes, cytoplasm and empty vacuoles, and they occur within dendrites which must expand to accomodate them. Some of these bodies measure 9 mu X 13 mu although the median size is about 6 mu in diameter. The membranes which make up the bulk of the complex bodies are assembled into sheets. These sheets are composed of 4 to as many as 100 layers and form undulating circular profiles within dendrites. The individual trilaminar membranes are about 60 A thick and exhibit a distinct tendency to pair within the sheets they form. The source of this great volume of membranes is not known since one finds neither a visible continuity with membranous organelles nor early stages in the formation of these membranous bodies.", "contents": "Membranous bodies in the cerebral cortex of aging rats: an electron microscope study. Large complex membranous bodies are described in the cerebral cortex of adult rats. Although these bodies are not very prevalent, they appear with increasing frequency as the age of the animal increases from 12 to 28 months. The membranous bodies are composed of varying amounts of membranes, cytoplasm and empty vacuoles, and they occur within dendrites which must expand to accomodate them. Some of these bodies measure 9 mu X 13 mu although the median size is about 6 mu in diameter. The membranes which make up the bulk of the complex bodies are assembled into sheets. These sheets are composed of 4 to as many as 100 layers and form undulating circular profiles within dendrites. The individual trilaminar membranes are about 60 A thick and exhibit a distinct tendency to pair within the sheets they form. The source of this great volume of membranes is not known since one finds neither a visible continuity with membranous organelles nor early stages in the formation of these membranous bodies."} {"id": "PMID:1262911", "title": "Ultrastructure of the axon reaction in the immature rat thalamus.", "content": "The axon reaction was studied using immature rats aged 4 or 14 days at the time of unilateral removal of the cingulate cortex. After survival times of one to 5 days they were sacrificed and the anterior thalamic nucleus was examined using ultrastructural methods. The degree of degenerative change was much more intense in the 4-day group where the center of the reactive area was characterized by pronounced lysis of the neuropil and the loss of most neurons. Dark neurons were observed in both groups but mitochondrial proliferation was restricted to the 14-day group. Evidence for microglial formation from pericytes was observed in the 4-day group while reactive astrocytes were observed in both groups. It was concluded that a rapid maturation of the thalamic injury response occurs between the 4th and the 14th day in the rat so that by the 14th day the response is similar in many respects to that of mature animals.", "contents": "Ultrastructure of the axon reaction in the immature rat thalamus. The axon reaction was studied using immature rats aged 4 or 14 days at the time of unilateral removal of the cingulate cortex. After survival times of one to 5 days they were sacrificed and the anterior thalamic nucleus was examined using ultrastructural methods. The degree of degenerative change was much more intense in the 4-day group where the center of the reactive area was characterized by pronounced lysis of the neuropil and the loss of most neurons. Dark neurons were observed in both groups but mitochondrial proliferation was restricted to the 14-day group. Evidence for microglial formation from pericytes was observed in the 4-day group while reactive astrocytes were observed in both groups. It was concluded that a rapid maturation of the thalamic injury response occurs between the 4th and the 14th day in the rat so that by the 14th day the response is similar in many respects to that of mature animals."} {"id": "PMID:1262913", "title": "Tolosa-Hunt syndrome: one cause of painful ophthalmoplegia.", "content": "The author reports 12 cases of Tolosa-Hunt syndrome, a benign steroid-resistant cryptogenic granuloma that presents as painful ophthalmoplegia. This syndrome is differentiated from other causes of painful ophthalmoplegia including tumors, aneurysms, collagen disease, specific infections, mucoceles, and benign granulomas of unknown etiology. These other conditions should be excluded by appropriate tests. Surgical exploration is not necessary if there is a prompt remission on steroid therapy.", "contents": "Tolosa-Hunt syndrome: one cause of painful ophthalmoplegia. The author reports 12 cases of Tolosa-Hunt syndrome, a benign steroid-resistant cryptogenic granuloma that presents as painful ophthalmoplegia. This syndrome is differentiated from other causes of painful ophthalmoplegia including tumors, aneurysms, collagen disease, specific infections, mucoceles, and benign granulomas of unknown etiology. These other conditions should be excluded by appropriate tests. Surgical exploration is not necessary if there is a prompt remission on steroid therapy."} {"id": "PMID:1262914", "title": "Lateral microsurgical approach to intraorbital tumors.", "content": "The authors describe their microsurgical lateral orbital approach to intraorbital tumors. In seven patients ultrasonic scanning, computerized axial tomography, polytomography, orbital venography, and arteriography have allowed precise intraorbital tumor localization relative to the optic nerve. The authors believe that circumscribed tumors superior, lateral, or inferior to the optic nerve can be safely and completely removed through a 30-35-mm lateral skin incision with microsurgical dissecting techniques. A combined neurosurgical-ophthalmological team approach is emphasized.", "contents": "Lateral microsurgical approach to intraorbital tumors. The authors describe their microsurgical lateral orbital approach to intraorbital tumors. In seven patients ultrasonic scanning, computerized axial tomography, polytomography, orbital venography, and arteriography have allowed precise intraorbital tumor localization relative to the optic nerve. The authors believe that circumscribed tumors superior, lateral, or inferior to the optic nerve can be safely and completely removed through a 30-35-mm lateral skin incision with microsurgical dissecting techniques. A combined neurosurgical-ophthalmological team approach is emphasized."} {"id": "PMID:1262915", "title": "Metastasis via ventriculoperitoneal shunt in patients with medulloblastoma.", "content": "The authors have routinely inserted a ventriculoperitoneal shunt in all patients with a posterior fossa tumor and hydrocephalus some 7-10 days prior to craniotomy. Forty-one patients with medulloblastoma were treated in this fashion and of these, four metastasized through the shunt and died of systemic metastases without evidence of recurrent tumor in their central nervous system. A millipore filter which can be incorporated in the shunt has been used by the authors during the past 18 months in an effort to prevent metastatic spread through the shunt.", "contents": "Metastasis via ventriculoperitoneal shunt in patients with medulloblastoma. The authors have routinely inserted a ventriculoperitoneal shunt in all patients with a posterior fossa tumor and hydrocephalus some 7-10 days prior to craniotomy. Forty-one patients with medulloblastoma were treated in this fashion and of these, four metastasized through the shunt and died of systemic metastases without evidence of recurrent tumor in their central nervous system. A millipore filter which can be incorporated in the shunt has been used by the authors during the past 18 months in an effort to prevent metastatic spread through the shunt."} {"id": "PMID:1262916", "title": "Infections complicating the use of external ventriculostomy.", "content": "The use of external ventriculostomy at our institution has been retrospectively analyzed to determine the incidence of cerebrospinal fluid sepsis. Placement of 65 ventriculostomies over a 2-year period resulted in three cases of complicating meningitis and ventriculitis (4.5%). Duration of ventriculostomy placement did not seem related to the rate of infection but the method of placement, the prophylactic antibiotics used, and the monitoring and collecting system employed may be important.", "contents": "Infections complicating the use of external ventriculostomy. The use of external ventriculostomy at our institution has been retrospectively analyzed to determine the incidence of cerebrospinal fluid sepsis. Placement of 65 ventriculostomies over a 2-year period resulted in three cases of complicating meningitis and ventriculitis (4.5%). Duration of ventriculostomy placement did not seem related to the rate of infection but the method of placement, the prophylactic antibiotics used, and the monitoring and collecting system employed may be important."} {"id": "PMID:1262917", "title": "Cerebrospinal fluid shunt infections with anaerobic diphtheroids (Propionibacterium species).", "content": "The clinical and laboratory findings in six cases of anaerobic diphtheroid infection of cerebrospinal fluid shunts are described. These organisms have been infrequently reported as a cause of shunt infections but our data indicate that such infections may be more common than currently appreciated. Propionibacterium species are common contaminants of cerebrospinal fluid specimens, but when isolated from the spinal fluid of a patient with a shunt who has symptoms and signs compatible with infection, the organism should not be dismissed as a contaminant. Fever was a constant finding frequently accompanied by signs of central nervous system dysfunction. Spinal fluid pleocytosis was usually limited to 1 to 200 cells and protein and sugar values were variable. The organisms grow slowly, therefore spinal fluid cultures should be held for at least 14 days before they are reported as negative.", "contents": "Cerebrospinal fluid shunt infections with anaerobic diphtheroids (Propionibacterium species). The clinical and laboratory findings in six cases of anaerobic diphtheroid infection of cerebrospinal fluid shunts are described. These organisms have been infrequently reported as a cause of shunt infections but our data indicate that such infections may be more common than currently appreciated. Propionibacterium species are common contaminants of cerebrospinal fluid specimens, but when isolated from the spinal fluid of a patient with a shunt who has symptoms and signs compatible with infection, the organism should not be dismissed as a contaminant. Fever was a constant finding frequently accompanied by signs of central nervous system dysfunction. Spinal fluid pleocytosis was usually limited to 1 to 200 cells and protein and sugar values were variable. The organisms grow slowly, therefore spinal fluid cultures should be held for at least 14 days before they are reported as negative."} {"id": "PMID:1262918", "title": "Cerebral arterial spasm. Part 4: in vitro effects of temperature, serotonin analogues, large nonphysiological concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery.", "content": "In vitro experiments were performed using a small volume chamber to study serotonin-induced contractions of the canine basilar artery. Temperature was found to have a profound effect on the artery's response to serotonin. Raising the temperature to 40 degrees C (104 degrees F) increased the maximum response by 20% and lowering the temperature by 10 degrees C caused a 40% reduction in the maximum contraction. Cumulative log-dose response curves for analogues of serotonin demonstrated a high degree of specificity for the serotonin receptor and large nonphysiological concentrations of serotonin caused relaxation of the contracted artery. Extracellular calcium was shown to be an absolute requirement for serotonin-induced contractions. Extracellular magnesium, in contrast, was shown to inhibit serotonin-induced contractions.", "contents": "Cerebral arterial spasm. Part 4: in vitro effects of temperature, serotonin analogues, large nonphysiological concentrations of serotonin, and extracellular calcium and magnesium on serotonin-induced contractions of the canine basilar artery. In vitro experiments were performed using a small volume chamber to study serotonin-induced contractions of the canine basilar artery. Temperature was found to have a profound effect on the artery's response to serotonin. Raising the temperature to 40 degrees C (104 degrees F) increased the maximum response by 20% and lowering the temperature by 10 degrees C caused a 40% reduction in the maximum contraction. Cumulative log-dose response curves for analogues of serotonin demonstrated a high degree of specificity for the serotonin receptor and large nonphysiological concentrations of serotonin caused relaxation of the contracted artery. Extracellular calcium was shown to be an absolute requirement for serotonin-induced contractions. Extracellular magnesium, in contrast, was shown to inhibit serotonin-induced contractions."} {"id": "PMID:1262919", "title": "Cerebral arterial spasm. Part 5: in vitro contractile activity of vasoactive agents including human CSF on human basilar and anterior cerebral arteries.", "content": "In vitro experiments were performed with a small volume chamber to determine the contractile activity of various vasoactive agents on human basilar and anterior cerebral arteries. Cumulative log-dose response curves were obtained for most of the agents tested including serotonin and three different prostaglandins; many of these curves were found to be similar to curves previously obtained with canine cerebral arteries. It was concluded from these similarities that canine cerebral arteries are a good in vitro model for studying human cerebral arterial spasm. It was also demonstrated that human cerebrospinal fluid, collected up to 17 days after a subarachnoid hemorrhage from patients with clinical and angiographic evidence of cerebral arterial spasm, would cause large, dose-dependent contractions in human anterior cerebral arteries.", "contents": "Cerebral arterial spasm. Part 5: in vitro contractile activity of vasoactive agents including human CSF on human basilar and anterior cerebral arteries. In vitro experiments were performed with a small volume chamber to determine the contractile activity of various vasoactive agents on human basilar and anterior cerebral arteries. Cumulative log-dose response curves were obtained for most of the agents tested including serotonin and three different prostaglandins; many of these curves were found to be similar to curves previously obtained with canine cerebral arteries. It was concluded from these similarities that canine cerebral arteries are a good in vitro model for studying human cerebral arterial spasm. It was also demonstrated that human cerebrospinal fluid, collected up to 17 days after a subarachnoid hemorrhage from patients with clinical and angiographic evidence of cerebral arterial spasm, would cause large, dose-dependent contractions in human anterior cerebral arteries."} {"id": "PMID:1262920", "title": "Unoperated subdural hematomas. Long-term follow-up study by brain scan and electroencephalography.", "content": "The authors report nine patients selected from over 100 patients with subdural hematomas successfully treated without surgery. These patients were followed for as long as 5 years. All had angiographically demonstrated subdural hematomas. Electroencephalograms (EEG) documented well the clinical improvement of the patient, but were poor guides to the true size of the hematoma, since EEG returns to normal early in the patient's course. Static scans are a better guide to the presence of a subdural hematoma, but they lag behind clinical improvement and usually remain abnormal for considerable periods of time after a major portion of the hematoma has been reabsorbed, and the patient is asymptomatic.", "contents": "Unoperated subdural hematomas. Long-term follow-up study by brain scan and electroencephalography. The authors report nine patients selected from over 100 patients with subdural hematomas successfully treated without surgery. These patients were followed for as long as 5 years. All had angiographically demonstrated subdural hematomas. Electroencephalograms (EEG) documented well the clinical improvement of the patient, but were poor guides to the true size of the hematoma, since EEG returns to normal early in the patient's course. Static scans are a better guide to the presence of a subdural hematoma, but they lag behind clinical improvement and usually remain abnormal for considerable periods of time after a major portion of the hematoma has been reabsorbed, and the patient is asymptomatic."} {"id": "PMID:1262921", "title": "Brain and bone scans in primary Ewing's sarcoma of the petrous bone.", "content": "The authors present a case in which primary Ewing's sarcoma of the right petrous pyramid in a 9-year-old girl showed no uptake on a 99mTc-pertechnetate nuclide angiogram. Intense uptake was present on a 99mTc-polyphosphate bone scan, but a static brain scan was only minimally abnormal. The diagnosis and treatment of Ewing's sarcoma are reviewed.", "contents": "Brain and bone scans in primary Ewing's sarcoma of the petrous bone. The authors present a case in which primary Ewing's sarcoma of the right petrous pyramid in a 9-year-old girl showed no uptake on a 99mTc-pertechnetate nuclide angiogram. Intense uptake was present on a 99mTc-polyphosphate bone scan, but a static brain scan was only minimally abnormal. The diagnosis and treatment of Ewing's sarcoma are reviewed."} {"id": "PMID:1262923", "title": "Parietal intradiploic encephalocele. Case report.", "content": "An unusual case is presented of an intradiploic encephalocele surrounding a cerebrospinal fluid cyst. The relationship of this developmental anomaly to the more commonly encountered midline encephalocele and isolated reports of temporal bone encephaloceles are discussed.", "contents": "Parietal intradiploic encephalocele. Case report. An unusual case is presented of an intradiploic encephalocele surrounding a cerebrospinal fluid cyst. The relationship of this developmental anomaly to the more commonly encountered midline encephalocele and isolated reports of temporal bone encephaloceles are discussed."} {"id": "PMID:1262924", "title": "Moyamoya disease as a cause of subarachnoid hemorrhage in a Negro patient. Case report.", "content": "The authors describe a case of subarachnoid hemorrhage secondary to moyamoya disease in an adult Negro. To the authors' knowledge, this is the first such case reported. Moyamoya, the Japanese word for \"puff of smoke,\" describes the characteristic angiographic appearance of the collateral arterial network associated with internal carotid artery occlusion. The cause is unknown. Treatment consists of supportive care; the prognosis is variable.", "contents": "Moyamoya disease as a cause of subarachnoid hemorrhage in a Negro patient. Case report. The authors describe a case of subarachnoid hemorrhage secondary to moyamoya disease in an adult Negro. To the authors' knowledge, this is the first such case reported. Moyamoya, the Japanese word for \"puff of smoke,\" describes the characteristic angiographic appearance of the collateral arterial network associated with internal carotid artery occlusion. The cause is unknown. Treatment consists of supportive care; the prognosis is variable."} {"id": "PMID:1262933", "title": "Evaluation of an integrated 133Xe regional pulmonary-function analyzer.", "content": "An integrated system for diagnostic, quantitative, static and dynamic, regional pulmonary-function analysis--both ventilation and perfusion--using 133Xe has recently been developed by Ohio-Nuclear. This paper considers this equipment in a clinical setting and describes the results obtained from 50 normal subjects. Functionally, the analyzer was found to be satisfactory and its operation simple and easy to learn. Patient discomfort is minimal and the complete ventilation-perfusion analysis can be performed and reported in less than 30 min. The results from normal subjects were comparable with published results.", "contents": "Evaluation of an integrated 133Xe regional pulmonary-function analyzer. An integrated system for diagnostic, quantitative, static and dynamic, regional pulmonary-function analysis--both ventilation and perfusion--using 133Xe has recently been developed by Ohio-Nuclear. This paper considers this equipment in a clinical setting and describes the results obtained from 50 normal subjects. Functionally, the analyzer was found to be satisfactory and its operation simple and easy to learn. Patient discomfort is minimal and the complete ventilation-perfusion analysis can be performed and reported in less than 30 min. The results from normal subjects were comparable with published results."} {"id": "PMID:1262934", "title": "Technetium-99m-glucoheptonate as a brain-scanning agent: critical comparison with pertechnetate.", "content": "Delayed 99mTc-glucoheptonate and pertechnetate scans were evaluated in a paired study for their ability to detect brain lesions. Glucoheptonate was found to be superior in eight of 17 cases of brain tumor and in two of ten patients with cerebral infarction. In addition, early (30 min) 99mTc-glucoheptonate brain scans were compared with delayed studies: the former were inferior in 48% of the cases. We conclude that 99mTc-glucoheptonate is a promising agent for delayed brain scanning, offering better lesion detection than pertechnetate.", "contents": "Technetium-99m-glucoheptonate as a brain-scanning agent: critical comparison with pertechnetate. Delayed 99mTc-glucoheptonate and pertechnetate scans were evaluated in a paired study for their ability to detect brain lesions. Glucoheptonate was found to be superior in eight of 17 cases of brain tumor and in two of ten patients with cerebral infarction. In addition, early (30 min) 99mTc-glucoheptonate brain scans were compared with delayed studies: the former were inferior in 48% of the cases. We conclude that 99mTc-glucoheptonate is a promising agent for delayed brain scanning, offering better lesion detection than pertechnetate."} {"id": "PMID:1262935", "title": "Stasis of 111In-DTPA in the posterior fossa in patients with cerebellar degeneration.", "content": "Prolonged stasis of 111In-DTPA was noted in the poterior fossa in two patients during cisternography. Both patients had clinical signs of cerebellar dysfunction and pneumoencephalographic evidence of marked cerebellar degeneration. Cisternography may be a useful adjunct in evaluation patients with suspected cerebellar atrophy.", "contents": "Stasis of 111In-DTPA in the posterior fossa in patients with cerebellar degeneration. Prolonged stasis of 111In-DTPA was noted in the poterior fossa in two patients during cisternography. Both patients had clinical signs of cerebellar dysfunction and pneumoencephalographic evidence of marked cerebellar degeneration. Cisternography may be a useful adjunct in evaluation patients with suspected cerebellar atrophy."} {"id": "PMID:1262936", "title": "The 99mTc-DTPA dynamic renal scan with deconvolution analysis.", "content": "Dynamic renal studies were performed with 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). The results were analyzed by the method of mathematical deconvolution in order to obtain the impulse response function of the kidney. Regional analysis of the kidney was attempted by evaluating the independent responses of the renal parenchyma and renal pelvis to a bolus injection of 99mTc-DTPA.", "contents": "The 99mTc-DTPA dynamic renal scan with deconvolution analysis. Dynamic renal studies were performed with 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA). The results were analyzed by the method of mathematical deconvolution in order to obtain the impulse response function of the kidney. Regional analysis of the kidney was attempted by evaluating the independent responses of the renal parenchyma and renal pelvis to a bolus injection of 99mTc-DTPA."} {"id": "PMID:1262937", "title": "Possible enhancement of 67Ga-citrate imaging by iron dextran.", "content": "The whole-body retention of 67Ga-citrate was studied in intact and in abscess-bearing rabbits. The abscess-to-muscle ratio was obtained using a data processor. Administration of iron dextran lowers the whole-body retention in both the intact and abscess-bearing animals. The optimum time for administering the iron dextran was 24 hr after the 67Ga-citrate injection. At this time, the abscess-to-muscle ratio was highest and the cathode-ray screen images showed lowered back-ground activity and much better definition of the lesion.", "contents": "Possible enhancement of 67Ga-citrate imaging by iron dextran. The whole-body retention of 67Ga-citrate was studied in intact and in abscess-bearing rabbits. The abscess-to-muscle ratio was obtained using a data processor. Administration of iron dextran lowers the whole-body retention in both the intact and abscess-bearing animals. The optimum time for administering the iron dextran was 24 hr after the 67Ga-citrate injection. At this time, the abscess-to-muscle ratio was highest and the cathode-ray screen images showed lowered back-ground activity and much better definition of the lesion."} {"id": "PMID:1262938", "title": "Diagnosis of hepatic hemangioma using multiple-radionuclide and ultrasound techniques.", "content": "Two cases of heptatic hemangioma are reported in which multiple-radionuclide and ultrasound techniques were combined in the diagnostic process. Blood pool imaging rather than perfusion imaging proved to be the most definitive diagnostic procedure. The application of radionuclide and ultrasound studies in the differential diagnosis of focal lesions of the liver is discussed.", "contents": "Diagnosis of hepatic hemangioma using multiple-radionuclide and ultrasound techniques. Two cases of heptatic hemangioma are reported in which multiple-radionuclide and ultrasound techniques were combined in the diagnostic process. Blood pool imaging rather than perfusion imaging proved to be the most definitive diagnostic procedure. The application of radionuclide and ultrasound studies in the differential diagnosis of focal lesions of the liver is discussed."} {"id": "PMID:1262939", "title": "Liver scan in Budd-Chiari syndrome.", "content": "Seventeen liver scans were performed in seven patients with occulsion of hepatic veins: the Budd-Chiari syndrome. When some, but not all liver veins were occluded, markedly diminished uptake over the affected segments was usually seen (absence of uptake may occur in acute infarction and in chronic cases). When all major liver veins are occluded, markedly diminished uptake is seen over the peripheral parts of the right and left lobes with a triangular midline area of normal or excessive activity. The latter effect is probably caused by uptake in segments surrounding the inferior vena cava (frequently the caudate lobe) that have direct venous drainage. This liver-scan appearance is characteristic enough to warrant consideration of the Budd-Chiari syndrome as the first diagnosis. Good correlation existed between selective venography and liver-scan findings. The usefulness of liver scans in the followup after portocaval shunting is illustrated in one patient.", "contents": "Liver scan in Budd-Chiari syndrome. Seventeen liver scans were performed in seven patients with occulsion of hepatic veins: the Budd-Chiari syndrome. When some, but not all liver veins were occluded, markedly diminished uptake over the affected segments was usually seen (absence of uptake may occur in acute infarction and in chronic cases). When all major liver veins are occluded, markedly diminished uptake is seen over the peripheral parts of the right and left lobes with a triangular midline area of normal or excessive activity. The latter effect is probably caused by uptake in segments surrounding the inferior vena cava (frequently the caudate lobe) that have direct venous drainage. This liver-scan appearance is characteristic enough to warrant consideration of the Budd-Chiari syndrome as the first diagnosis. Good correlation existed between selective venography and liver-scan findings. The usefulness of liver scans in the followup after portocaval shunting is illustrated in one patient."} {"id": "PMID:1262940", "title": "Soft-tissue concentration of 99mTc-phosphates associated with injections of iron dextran complex.", "content": "An unusual concentration of 99mTc-phosphates appeared in the gluteal area in bone scans of three patients who had recently had intramuscular injections of iron dextran complex. These cases indicate one more cause for extraosseous accumulation of these bone-seeking radiopharmaceuticals.", "contents": "Soft-tissue concentration of 99mTc-phosphates associated with injections of iron dextran complex. An unusual concentration of 99mTc-phosphates appeared in the gluteal area in bone scans of three patients who had recently had intramuscular injections of iron dextran complex. These cases indicate one more cause for extraosseous accumulation of these bone-seeking radiopharmaceuticals."} {"id": "PMID:1262941", "title": "Arteriographically confirmed focal defect in colloid spleen scan with no gross pathologic lession: case report.", "content": "A focal avascular defect in an enlarged spleen, clearly shown both by 99mTc-sulfur colloid scanning and by celiac angiography, could not be associated with any gross pathologic abnormality at splenectomy. Vascular lesions can probably produce focal defects on the scan in the absence of infarction.", "contents": "Arteriographically confirmed focal defect in colloid spleen scan with no gross pathologic lession: case report. A focal avascular defect in an enlarged spleen, clearly shown both by 99mTc-sulfur colloid scanning and by celiac angiography, could not be associated with any gross pathologic abnormality at splenectomy. Vascular lesions can probably produce focal defects on the scan in the absence of infarction."} {"id": "PMID:1262942", "title": "Combination of renal and adrenal scanning in the diagnosis of renovascular hypertension: case report.", "content": "Superimposition of an adrenal scan on a renal scan revealed a kidney defect not appreciated on the renal scan alone. The defect proved to be ischemia of the upper pole of the kidney. Resection of the lesion alleviated the patient's hypertension.", "contents": "Combination of renal and adrenal scanning in the diagnosis of renovascular hypertension: case report. Superimposition of an adrenal scan on a renal scan revealed a kidney defect not appreciated on the renal scan alone. The defect proved to be ischemia of the upper pole of the kidney. Resection of the lesion alleviated the patient's hypertension."} {"id": "PMID:1262943", "title": "Effects of prior administration of Sn(II) complexes on in vivo distribution of 99mTc-pertechnetate.", "content": "This report evaluates the effect of prior administration of several clinically used Sn(II)-containing agents on in vivo distribution of 99mTc. Abnormal binding of 99mTc to red blood cells can occur after administration of pertechnetate to patients who have previously received tin-containing agents. Increased blood levels of tin from other causes may have similar effects.", "contents": "Effects of prior administration of Sn(II) complexes on in vivo distribution of 99mTc-pertechnetate. This report evaluates the effect of prior administration of several clinically used Sn(II)-containing agents on in vivo distribution of 99mTc. Abnormal binding of 99mTc to red blood cells can occur after administration of pertechnetate to patients who have previously received tin-containing agents. Increased blood levels of tin from other causes may have similar effects."} {"id": "PMID:1262944", "title": "New preparation method for 99mTc-phytate.", "content": "A new method is described in which Pt-Sn or Sn-Sn electrodes are used to activate 99mTcO4-. The 99mTc is incorporated into phytic acid by stannous ion released from a tin anode by the corrosive reaction. The most suitable pH for labeling phytic acid by this method was below 5 and the 99mTc-phytate formed could be precipitatedd with Ca+2 at a pH above 3.5. Though 99mTc-phytate is soluble in aqueous solution, it forms an insoluble species with Ca+2 in vivo and is trapped in the reticuloendothelial system. More than 93% of the 99mTc-phytate localized in the liver of mice; here its biologic half-time is about 112 hr. The 99mTc-phytate prepared by this method promises to be useful as a liver-scanning agent. Since our method does not require an applied electric potential, it appears to be one of the most convenient methods for labeling compounds with 99mTc.", "contents": "New preparation method for 99mTc-phytate. A new method is described in which Pt-Sn or Sn-Sn electrodes are used to activate 99mTcO4-. The 99mTc is incorporated into phytic acid by stannous ion released from a tin anode by the corrosive reaction. The most suitable pH for labeling phytic acid by this method was below 5 and the 99mTc-phytate formed could be precipitatedd with Ca+2 at a pH above 3.5. Though 99mTc-phytate is soluble in aqueous solution, it forms an insoluble species with Ca+2 in vivo and is trapped in the reticuloendothelial system. More than 93% of the 99mTc-phytate localized in the liver of mice; here its biologic half-time is about 112 hr. The 99mTc-phytate prepared by this method promises to be useful as a liver-scanning agent. Since our method does not require an applied electric potential, it appears to be one of the most convenient methods for labeling compounds with 99mTc."} {"id": "PMID:1262945", "title": "Preparation and use of 123I-labeled highly iodinated fibrinogen for imaging deep-vein thrombi.", "content": "A method for producing protein-iodination-grade 123I suitable for use with a compact bio-medical cyclotron is reported. The preparation of highly iodinated fibrinogen (25 123I atoms per molecule) is described, and its successful use as a thrombus-imaging agent in experimental animals is reported. This new agent clears from the blood faster than conventional radioiodinated fibrinogen and gives higher thrombus-to-blood activity ratios. Thus, the detection of deep-vein thrombi in areas of large blood pool is enhanced, and images can be obtained sooner after administration of the radiopharmaceutical. Induced 4--8-hr-old femoral-vien thrombi in dogs can be well visualized with a scintillation camera as early as 4 hr and as late as 15 hr after administration of 1 mCi of 123I-labeled highly iodinated fibrinogen.", "contents": "Preparation and use of 123I-labeled highly iodinated fibrinogen for imaging deep-vein thrombi. A method for producing protein-iodination-grade 123I suitable for use with a compact bio-medical cyclotron is reported. The preparation of highly iodinated fibrinogen (25 123I atoms per molecule) is described, and its successful use as a thrombus-imaging agent in experimental animals is reported. This new agent clears from the blood faster than conventional radioiodinated fibrinogen and gives higher thrombus-to-blood activity ratios. Thus, the detection of deep-vein thrombi in areas of large blood pool is enhanced, and images can be obtained sooner after administration of the radiopharmaceutical. Induced 4--8-hr-old femoral-vien thrombi in dogs can be well visualized with a scintillation camera as early as 4 hr and as late as 15 hr after administration of 1 mCi of 123I-labeled highly iodinated fibrinogen."} {"id": "PMID:1262946", "title": "Collimation for imaging the myocardium.", "content": "Line-source response functions and modulation transfer functions (MTFs) were used to compare the resolution obtained with four myocardial-imaging agents: 129Cs, 43K, 13N-ammonia, and 81Rb contamination. When an Anger camera with pinhole collimator was used, the order of decreasing resolution was 129Cs, 43K, 13N, and 81Rb. Two techniques were employed to determine the extent to which spatial resolution could be improved. The first, involving the addition of lateral shielding, improved the MTFs for all the agents studied. The second, which utilized a subtraction mode, gave the best overall results. With the second method the MTF curves for 129Cs and 43K became very similar and were superior to both 81Rb and 13N. Both techniques were found useful in improving the spatial resolution of certain myocardial-imaging agents by reducing or eliminating the effects of penetration of the pinhole collimator walls by high-energy photons.", "contents": "Collimation for imaging the myocardium. Line-source response functions and modulation transfer functions (MTFs) were used to compare the resolution obtained with four myocardial-imaging agents: 129Cs, 43K, 13N-ammonia, and 81Rb contamination. When an Anger camera with pinhole collimator was used, the order of decreasing resolution was 129Cs, 43K, 13N, and 81Rb. Two techniques were employed to determine the extent to which spatial resolution could be improved. The first, involving the addition of lateral shielding, improved the MTFs for all the agents studied. The second, which utilized a subtraction mode, gave the best overall results. With the second method the MTF curves for 129Cs and 43K became very similar and were superior to both 81Rb and 13N. Both techniques were found useful in improving the spatial resolution of certain myocardial-imaging agents by reducing or eliminating the effects of penetration of the pinhole collimator walls by high-energy photons."} {"id": "PMID:1262947", "title": "Assay of 32P-sodium phosphate using a commercial dose calibrator.", "content": "Dose calibrators are not usually used to measure the activity of pure beta-emitting radionuclides. In this work, the activity of 32P-sodium phosphate was accurately measured with a Capintec CRC-2 dose calibrator. Using a calibration knob setting of 012 on the 1-mCi range, the 32P dose (in mCi) could be calculated directly simply by multiplying the instrument readout by 10. The dose calibrator response was found to be linear at this knob setting and moderate alterations in geometry produced no significant changes.", "contents": "Assay of 32P-sodium phosphate using a commercial dose calibrator. Dose calibrators are not usually used to measure the activity of pure beta-emitting radionuclides. In this work, the activity of 32P-sodium phosphate was accurately measured with a Capintec CRC-2 dose calibrator. Using a calibration knob setting of 012 on the 1-mCi range, the 32P dose (in mCi) could be calculated directly simply by multiplying the instrument readout by 10. The dose calibrator response was found to be linear at this knob setting and moderate alterations in geometry produced no significant changes."} {"id": "PMID:1262948", "title": "Usefulness of brain scans in metastatic carcinoma of the lung.", "content": "The usefulness of brain scans for detecting unsuspected cerebral metastasis in patients with carcinoma of the lung was studied in a group of 35 such patients who had had routine brain scans as part of the initial evaluation. Seven (20%) had scans that were positive for tumor, but six of these seven had neurologic deficits corresponding to the brain-scan abnormality. Routine brain scans for evaluation of carcinoma of the lung are not justified if neurologic examination is normal.", "contents": "Usefulness of brain scans in metastatic carcinoma of the lung. The usefulness of brain scans for detecting unsuspected cerebral metastasis in patients with carcinoma of the lung was studied in a group of 35 such patients who had had routine brain scans as part of the initial evaluation. Seven (20%) had scans that were positive for tumor, but six of these seven had neurologic deficits corresponding to the brain-scan abnormality. Routine brain scans for evaluation of carcinoma of the lung are not justified if neurologic examination is normal."} {"id": "PMID:1262949", "title": "Radiation hazards from 241Am sources used in thyroid studies.", "content": "The neutron and gamma photon doses corresponding to the neck and eye level from an 241AmO2 source used in thyroid studies have been theoretically estimated. The radiation hazard to the patient is found to be not significant.", "contents": "Radiation hazards from 241Am sources used in thyroid studies. The neutron and gamma photon doses corresponding to the neck and eye level from an 241AmO2 source used in thyroid studies have been theoretically estimated. The radiation hazard to the patient is found to be not significant."} {"id": "PMID:1262950", "title": "A simple and rapid radioimmunoassay of triiodothyronine in unextracted serum.", "content": "A simple, accurate, and rapid procedure for radioimmunoassay (RIA) of triiodothyronine (T3) is described. Serum is denatured by sodium trichloroacetate and the T3 released is allowed to react with 125I-T3-labeled T3 anti-serum. The displaced 125I-T3 is rapidly taken up by an anionic-resin sponge, and this uptake is linearly related to serum T3 concentration. The entire assay procedure was completed in the same tube in about 1 hr. The T3 antibody was specific, and T4-to-T3 conversion in the assay did not occur. Recovery of exogenously added T3 was virtually complete. The mean T3 concentration in 92 euthyroid subjects (142 ng/100 ml) is comparable to the values described in a number of radioimmunoassays for T3.", "contents": "A simple and rapid radioimmunoassay of triiodothyronine in unextracted serum. A simple, accurate, and rapid procedure for radioimmunoassay (RIA) of triiodothyronine (T3) is described. Serum is denatured by sodium trichloroacetate and the T3 released is allowed to react with 125I-T3-labeled T3 anti-serum. The displaced 125I-T3 is rapidly taken up by an anionic-resin sponge, and this uptake is linearly related to serum T3 concentration. The entire assay procedure was completed in the same tube in about 1 hr. The T3 antibody was specific, and T4-to-T3 conversion in the assay did not occur. Recovery of exogenously added T3 was virtually complete. The mean T3 concentration in 92 euthyroid subjects (142 ng/100 ml) is comparable to the values described in a number of radioimmunoassays for T3."} {"id": "PMID:1262962", "title": "Diagnosis of cirrhosis and hepatitis by quantitative hepatic and other reticuloendothelial clearance rates.", "content": "Although methods for measuring colloid clearance rates have been described, they are not commonly used. Rather, most clinicians rely on the relative radiocolloid accummulation in the liver and spleen as estimated by visual inspection of liver scans. This method lacks objectivity, however, and only indirectly reflects the rate of radiocolloid clearance. We have developed a noninvasive kinetic technique for measuring radiocolloid clearance by the liver, spleen, and other reticuloendothelial tissues. The clerance-rate constants obtained by this technique appear to differentiate among cirrhosis, fatty metamorphosis, hepatitis, and normal function. In normal subjects, the mean clearance-rate constants for the liver, spleen, and extrahepatosplenic reticuloendothelial system were 16.0, 1.4, and 3.4 ml/min per 100 ml of plasma, respectively. The mean hepatic clearance-rate constant was normal in hepatitis (16.8 ml/min per 100 ml), reduced in cirrhosis (5.7), and slightly reduced in fatty metamorphosis (10.4). Both the hepatic-to-splenic and the hepatic-to-extrahepatosplenic ratios of clearance-rate constants were reduced in cirrhosis and slightly reduced in fatty metamorphosis and hepatitis. Interestingly, the splenic clearance-rate constants were normal in these three diseases.", "contents": "Diagnosis of cirrhosis and hepatitis by quantitative hepatic and other reticuloendothelial clearance rates. Although methods for measuring colloid clearance rates have been described, they are not commonly used. Rather, most clinicians rely on the relative radiocolloid accummulation in the liver and spleen as estimated by visual inspection of liver scans. This method lacks objectivity, however, and only indirectly reflects the rate of radiocolloid clearance. We have developed a noninvasive kinetic technique for measuring radiocolloid clearance by the liver, spleen, and other reticuloendothelial tissues. The clerance-rate constants obtained by this technique appear to differentiate among cirrhosis, fatty metamorphosis, hepatitis, and normal function. In normal subjects, the mean clearance-rate constants for the liver, spleen, and extrahepatosplenic reticuloendothelial system were 16.0, 1.4, and 3.4 ml/min per 100 ml of plasma, respectively. The mean hepatic clearance-rate constant was normal in hepatitis (16.8 ml/min per 100 ml), reduced in cirrhosis (5.7), and slightly reduced in fatty metamorphosis (10.4). Both the hepatic-to-splenic and the hepatic-to-extrahepatosplenic ratios of clearance-rate constants were reduced in cirrhosis and slightly reduced in fatty metamorphosis and hepatitis. Interestingly, the splenic clearance-rate constants were normal in these three diseases."} {"id": "PMID:1262963", "title": "Specificity of 99mTc-pertechnetate in scintigraphic diagnosis of Meckel's diverticulum: review of 100 cases.", "content": "Numerous reports in the recent literature have questioned the value of abdominal scanning with pertechnetate in the diagnosis of Meckel's diverticulum. In an attempt to evaluate further the specificity of pertechnetate in this condition, the clinical data and scintigrams of 100 patients with suspected Meckel's diverticulum were reviewed. The scintigram correctly identified Meckel's diverticulum before operation in seven of eight patients. One false-negative study occurred in 33 patients who underwent laparotomy. Conditions suggested as possible causes of false-positive studies (hydronephrosis, arteriovenous malformations, and intussusception) were found to give negative scans.", "contents": "Specificity of 99mTc-pertechnetate in scintigraphic diagnosis of Meckel's diverticulum: review of 100 cases. Numerous reports in the recent literature have questioned the value of abdominal scanning with pertechnetate in the diagnosis of Meckel's diverticulum. In an attempt to evaluate further the specificity of pertechnetate in this condition, the clinical data and scintigrams of 100 patients with suspected Meckel's diverticulum were reviewed. The scintigram correctly identified Meckel's diverticulum before operation in seven of eight patients. One false-negative study occurred in 33 patients who underwent laparotomy. Conditions suggested as possible causes of false-positive studies (hydronephrosis, arteriovenous malformations, and intussusception) were found to give negative scans."} {"id": "PMID:1262964", "title": "Intestinal concentration of 99mTc-pertechnetate into isolated loops of rat bowel.", "content": "In scanning patients for Meckel's diverticulum, the colon occasionally visualizes more rapidly than would be expected simply from gastric secretion and intestinal transit. To gain a better understanding of the intestinal physiology of pertechnetate and thereby to make a more intelligent interpretation of abdominal scans, segments of the gastrointestinal tract of Sprague-Dawley rats were isolated by transection between double ligations. After abdominal closure, the animals received an intravenous injection of 99mTcO4 and were killed at 30, 45, or 150 min after injection. Technetium concentrations in the stomach, colon, and appendiceal contents increased significantly with time after dosing, and after 30 min technetium could be clearly imaged in the stomach, upper small intestine, appendix, and colon. These results suggest that technetium is actively secreted by the intestinal mucosa. Additionally, the results indicate caution in the interpretation of scans in patients with suspected Meckel's diverticulum since, in the rat and probably in the human, significant amounts of technetium can accumulate in the gut apart from gastric secretion and intestinal transit.", "contents": "Intestinal concentration of 99mTc-pertechnetate into isolated loops of rat bowel. In scanning patients for Meckel's diverticulum, the colon occasionally visualizes more rapidly than would be expected simply from gastric secretion and intestinal transit. To gain a better understanding of the intestinal physiology of pertechnetate and thereby to make a more intelligent interpretation of abdominal scans, segments of the gastrointestinal tract of Sprague-Dawley rats were isolated by transection between double ligations. After abdominal closure, the animals received an intravenous injection of 99mTcO4 and were killed at 30, 45, or 150 min after injection. Technetium concentrations in the stomach, colon, and appendiceal contents increased significantly with time after dosing, and after 30 min technetium could be clearly imaged in the stomach, upper small intestine, appendix, and colon. These results suggest that technetium is actively secreted by the intestinal mucosa. Additionally, the results indicate caution in the interpretation of scans in patients with suspected Meckel's diverticulum since, in the rat and probably in the human, significant amounts of technetium can accumulate in the gut apart from gastric secretion and intestinal transit."} {"id": "PMID:1262965", "title": "Techniques for positron scintigraphy of the brain.", "content": "Positron scintigrams were obtained in normal subjects and in patients with intracranial tumors and cerebral vascular disease, using a multicrystal positron camera. The radiopharmaceuticals were 68Ga complexed with adenosine triphosphate (68Ga-ATP), 13N-ammonia (13NH3), and 15O2. Six clinical cases are described to illustrate the different cerebral distributions of intravenously administered 68Ga-ATP, 13NH3, and inhaled 15O2. The possible value of these agents in the study of cerebral metabolism and in differential diagnosis of intracranial disease is discussed.", "contents": "Techniques for positron scintigraphy of the brain. Positron scintigrams were obtained in normal subjects and in patients with intracranial tumors and cerebral vascular disease, using a multicrystal positron camera. The radiopharmaceuticals were 68Ga complexed with adenosine triphosphate (68Ga-ATP), 13N-ammonia (13NH3), and 15O2. Six clinical cases are described to illustrate the different cerebral distributions of intravenously administered 68Ga-ATP, 13NH3, and inhaled 15O2. The possible value of these agents in the study of cerebral metabolism and in differential diagnosis of intracranial disease is discussed."} {"id": "PMID:1262966", "title": "Survey of radioactive agents for in vitro labeling of phagocytic leukocytes. II. Particles.", "content": "When various radioactive particles are incubated and tumbled in concentrated suspensions of blood phagocytes at body temperature for 1 hr, they bind to the phagocytic cells with a labeling yield of 30-40%. In vitro experiments show that, for some radioactive colloids, a sizeable fraction of the total cellular binding results from nonspecific surface adsorption to other cells and from reversible surface adsorption to phagocytes without engulfment. No completely satisfactory in vitro methods have been found for separating leukocytes with completely engulfed particles from those with surface-adherent particles; nonetheless, surface adherence can be partially reversed by 20% acid citrate dextrose (ACD) solution or by an excess of nonradioactive colloid. Gelatinization of colloidal particles tends to increase their binding to phagocytic cells but also increases the degree of nonspecific adherence to other cells. Technetium-99m-millimicrospheres, 0.5-2 mum in diameter, are optimal in size for phagocytosis by neutrophils, and their non-specific adherence to other cells is minimal. Because of the microspheres' poor stability in aqueous suspension, however, it is technically difficult to separate free from phagocytosed radioactivity after cell incubation. The highly stable small-particle colloids (less than 0.1 mum), such as 198Au-colloid or 111In-colloid without iron carrier, are phagocytosed poorly or not at all by neutrophils, although they are engulfed by mononuclear cells.", "contents": "Survey of radioactive agents for in vitro labeling of phagocytic leukocytes. II. Particles. When various radioactive particles are incubated and tumbled in concentrated suspensions of blood phagocytes at body temperature for 1 hr, they bind to the phagocytic cells with a labeling yield of 30-40%. In vitro experiments show that, for some radioactive colloids, a sizeable fraction of the total cellular binding results from nonspecific surface adsorption to other cells and from reversible surface adsorption to phagocytes without engulfment. No completely satisfactory in vitro methods have been found for separating leukocytes with completely engulfed particles from those with surface-adherent particles; nonetheless, surface adherence can be partially reversed by 20% acid citrate dextrose (ACD) solution or by an excess of nonradioactive colloid. Gelatinization of colloidal particles tends to increase their binding to phagocytic cells but also increases the degree of nonspecific adherence to other cells. Technetium-99m-millimicrospheres, 0.5-2 mum in diameter, are optimal in size for phagocytosis by neutrophils, and their non-specific adherence to other cells is minimal. Because of the microspheres' poor stability in aqueous suspension, however, it is technically difficult to separate free from phagocytosed radioactivity after cell incubation. The highly stable small-particle colloids (less than 0.1 mum), such as 198Au-colloid or 111In-colloid without iron carrier, are phagocytosed poorly or not at all by neutrophils, although they are engulfed by mononuclear cells."} {"id": "PMID:1262967", "title": "Design and performance characteristics of a whole-body positron transaxial tomograph.", "content": "A whole-body positron-emission transaxial tomograph (PETT III) is described in detail and evaluated in terms of resolution, accuracy, and efficiency. The PETT III utilizes annihilation coincidence detection to provide spatial resolution; high sensitivity is achieved by using 48 Nal(tl) detectors set in a hexagonal array with a multiple-coincidence logic. The assumptions and approximations made in the reconstruction and their effect on image quality are discussed. Phantom studies shows the depth-independent resolution and response of PETT III, as well as its ability to recover activity distribution quantitatively in the cross section measured. Images obtained with patients and normal volunteers show the potential clinical utility of PETT III.", "contents": "Design and performance characteristics of a whole-body positron transaxial tomograph. A whole-body positron-emission transaxial tomograph (PETT III) is described in detail and evaluated in terms of resolution, accuracy, and efficiency. The PETT III utilizes annihilation coincidence detection to provide spatial resolution; high sensitivity is achieved by using 48 Nal(tl) detectors set in a hexagonal array with a multiple-coincidence logic. The assumptions and approximations made in the reconstruction and their effect on image quality are discussed. Phantom studies shows the depth-independent resolution and response of PETT III, as well as its ability to recover activity distribution quantitatively in the cross section measured. Images obtained with patients and normal volunteers show the potential clinical utility of PETT III."} {"id": "PMID:1262968", "title": "Influence of dietary peroxides, selenium and vitamin E on glutathione peroxidase of the gastrointestinal tract.", "content": "The influence of dietary peroxides, vitamin E and selenium on glutathione peroxidase (GSH-Px) activity in the gastrointestinal tract of the rat was investigated. Feeding 7% oxidized stripped corn oid (peroxide value 1,000) in a diet adequate in selenium and vitamin E increased the specific activity of GSH-Px in the stomach mucosa. Feeding oxidized oil produced an increase in the wet weight of the intestinal mucosa which was associated with a decrease in the specific activity of the enzyme. Total GSH-Px activity in the intestinal mucosa was unchanged or moderately increased. These changes were unaffected by the presence of vitamin E in the diet. Dietary peroxides had no effect on GSH-Px activity in the plasma or in the perirenal and paraepididymal adipose tissues. Subacute vitamin E deficiency had no consistent effect on the activity of the enzyme in several tissues examined. In rats fed a Se deficient diet glutathione peroxidase activity decreased markedly in most tissues but only slightly in the intestinal mucosa. The moderate decrease in the intestine may be explained by the accessibility of residual dietary Se to the mucosal cells. The role of Se in the detoxification of peroxides in foods and the response of gastrointestinal GSH-Px to dietary peroxides are discussed.", "contents": "Influence of dietary peroxides, selenium and vitamin E on glutathione peroxidase of the gastrointestinal tract. The influence of dietary peroxides, vitamin E and selenium on glutathione peroxidase (GSH-Px) activity in the gastrointestinal tract of the rat was investigated. Feeding 7% oxidized stripped corn oid (peroxide value 1,000) in a diet adequate in selenium and vitamin E increased the specific activity of GSH-Px in the stomach mucosa. Feeding oxidized oil produced an increase in the wet weight of the intestinal mucosa which was associated with a decrease in the specific activity of the enzyme. Total GSH-Px activity in the intestinal mucosa was unchanged or moderately increased. These changes were unaffected by the presence of vitamin E in the diet. Dietary peroxides had no effect on GSH-Px activity in the plasma or in the perirenal and paraepididymal adipose tissues. Subacute vitamin E deficiency had no consistent effect on the activity of the enzyme in several tissues examined. In rats fed a Se deficient diet glutathione peroxidase activity decreased markedly in most tissues but only slightly in the intestinal mucosa. The moderate decrease in the intestine may be explained by the accessibility of residual dietary Se to the mucosal cells. The role of Se in the detoxification of peroxides in foods and the response of gastrointestinal GSH-Px to dietary peroxides are discussed."} {"id": "PMID:1262969", "title": "Free amino acid patterns and the distribution of 14C from [U-14C]-L-Leucine, [U-14C]-L-Lysine, and [U-14C]-L-Alanine in the tissues of young adult rats.", "content": "In studies designed to evaluate the role of the liver and muscle in modifying the plasma amino acid response, three levels of dietary amino acids, 3.6%, 4.8% and 6.0% were fed to three groups of young adult male rats for 2 weeks. After fasting, either [U-14C]-L-leucine, [U-14C]-L-lysine or [U-14C]-L-alanine was administered intragastrically with a portion of diet. After a 4.5 hour fast, rats were killed. Distribution of radioactivity was evaluated in trichloroacetic acid (TCA) supernatants and lipid-extracted precipitates of plasma, liver and gastrocnemius muscle, and in expired CO2. Free amino acids were measured and specific activities of amino acids were determined. Rats fed 6.0% or 4.8% amino acids lost less weight than those fed 3.6%. A high percentage of radioactivity from 14C-leucine and 14C-lysine was recovered in the lipid-extracted precipitate. TCA supernatants from rats fed 14C-leucine contained low levels of radioactivity. A large percentage (60%) of the radioactivity from 14C-alanine was expired in 14CO2. The percentages of alanine found in TCA precipitates were very low. Significant increases in concentration associated with increments in dietary amino acids occurred in plasma free isoleucine, leucine, valine and tyrosine; liver free histidine; and muscle free leucine and threonine. Concentrations of many amino acids were depressed in the muscle of rats fed 4.8% amino acids whereas they increased in response to 6.0%. Protein and free amino acid specific activities indicated no change in rates of protein synthesis. Data from this type of experiment may assist in interpreting the role of the liver and muscle in modifying the plasma amino acid response to dietary amino acids.", "contents": "Free amino acid patterns and the distribution of 14C from [U-14C]-L-Leucine, [U-14C]-L-Lysine, and [U-14C]-L-Alanine in the tissues of young adult rats. In studies designed to evaluate the role of the liver and muscle in modifying the plasma amino acid response, three levels of dietary amino acids, 3.6%, 4.8% and 6.0% were fed to three groups of young adult male rats for 2 weeks. After fasting, either [U-14C]-L-leucine, [U-14C]-L-lysine or [U-14C]-L-alanine was administered intragastrically with a portion of diet. After a 4.5 hour fast, rats were killed. Distribution of radioactivity was evaluated in trichloroacetic acid (TCA) supernatants and lipid-extracted precipitates of plasma, liver and gastrocnemius muscle, and in expired CO2. Free amino acids were measured and specific activities of amino acids were determined. Rats fed 6.0% or 4.8% amino acids lost less weight than those fed 3.6%. A high percentage of radioactivity from 14C-leucine and 14C-lysine was recovered in the lipid-extracted precipitate. TCA supernatants from rats fed 14C-leucine contained low levels of radioactivity. A large percentage (60%) of the radioactivity from 14C-alanine was expired in 14CO2. The percentages of alanine found in TCA precipitates were very low. Significant increases in concentration associated with increments in dietary amino acids occurred in plasma free isoleucine, leucine, valine and tyrosine; liver free histidine; and muscle free leucine and threonine. Concentrations of many amino acids were depressed in the muscle of rats fed 4.8% amino acids whereas they increased in response to 6.0%. Protein and free amino acid specific activities indicated no change in rates of protein synthesis. Data from this type of experiment may assist in interpreting the role of the liver and muscle in modifying the plasma amino acid response to dietary amino acids."} {"id": "PMID:1262970", "title": "Changes in diet and patterns of feeding activity of developing rats.", "content": "The purpose of this study was to determine the amount of milk and stock diet consumed by rats during postnatal development and the extent to which they feed in circadian rhythms when weaned naturally by their dams or when separated from their dams at age 21 days. One approach used in several experiments was to record feed bin weight losses at circadian intervals. The second approach was to analyze the stomach contents of rats killed at circadian intervals at representative ages. Contents were inspected, freeze-dried, weighed and assayed for fat by extraction with solvent. The difference in fat between rat milk solids and stock diet was the basis for estimating proportions of stock diet and milk. The results indicate that 1) natural weaning occurs progressively from 14 to 30 days after birth, with an accelerated phase between 18 and 25 days; 2) pups up to 8 days old and their dams feed mostly by light and darkness, respectively; 3) circadian variations in feeding are weak and inconsistent in 10 to 20 day old pups and their dams; 4) at 21 days pups and dams begin to feed mostly in darkness; 5) the proportions of food consumed by light and darkness approach those of the adult by age 29 days when rats are weaned naturally, and by 25 days when weaned at 21 days; and 6) progression into the nocturnal feeding pattern may be disturbed if larger litters are not provided with sufficient space.", "contents": "Changes in diet and patterns of feeding activity of developing rats. The purpose of this study was to determine the amount of milk and stock diet consumed by rats during postnatal development and the extent to which they feed in circadian rhythms when weaned naturally by their dams or when separated from their dams at age 21 days. One approach used in several experiments was to record feed bin weight losses at circadian intervals. The second approach was to analyze the stomach contents of rats killed at circadian intervals at representative ages. Contents were inspected, freeze-dried, weighed and assayed for fat by extraction with solvent. The difference in fat between rat milk solids and stock diet was the basis for estimating proportions of stock diet and milk. The results indicate that 1) natural weaning occurs progressively from 14 to 30 days after birth, with an accelerated phase between 18 and 25 days; 2) pups up to 8 days old and their dams feed mostly by light and darkness, respectively; 3) circadian variations in feeding are weak and inconsistent in 10 to 20 day old pups and their dams; 4) at 21 days pups and dams begin to feed mostly in darkness; 5) the proportions of food consumed by light and darkness approach those of the adult by age 29 days when rats are weaned naturally, and by 25 days when weaned at 21 days; and 6) progression into the nocturnal feeding pattern may be disturbed if larger litters are not provided with sufficient space."} {"id": "PMID:1262971", "title": "Alteration of glucose tolerance by dietary L-tryptophan in rats.", "content": "L-Tryptophan is known to have pharmacological effects on carbohydrate metabolism. In a scrutiny for possible physiological relationships, intravenous glucose tolerance was measured in rats fed various diets of defined L-tryptophan-content. Within 14 days, animals which had been fed a tryptophan-deficient diet diet removed excess glucose from their blood at a reduced rate. This decreased tolerance to glucose was dose dependent to dietary L-tryptophan and the intolerance was reversed by feeding a complete diet. The intolerance was not dependent on dietary protein source, not reversed by added niacin or vitamin B-6, not a necessary consequence of decreased food consumption and growth, and not duplicated by a lack of dietary lysine. The results suggest that dietary L-tryptophan is active in physiological regulation of carbohydrate metabolism.", "contents": "Alteration of glucose tolerance by dietary L-tryptophan in rats. L-Tryptophan is known to have pharmacological effects on carbohydrate metabolism. In a scrutiny for possible physiological relationships, intravenous glucose tolerance was measured in rats fed various diets of defined L-tryptophan-content. Within 14 days, animals which had been fed a tryptophan-deficient diet diet removed excess glucose from their blood at a reduced rate. This decreased tolerance to glucose was dose dependent to dietary L-tryptophan and the intolerance was reversed by feeding a complete diet. The intolerance was not dependent on dietary protein source, not reversed by added niacin or vitamin B-6, not a necessary consequence of decreased food consumption and growth, and not duplicated by a lack of dietary lysine. The results suggest that dietary L-tryptophan is active in physiological regulation of carbohydrate metabolism."} {"id": "PMID:1262972", "title": "Nitrogen metabolism and reproductive response of gravid swine fed an arginine-free diet during the last 84 days of gestation.", "content": "Based upon nitrogen retention and urinary excretion of orotic and citric acid, previous experiments have shown that the gravid gilt does not require a dietary source of arginine during late gestation. This experiment was designed to evaluate effects of feeding an arginine-free diet for a major portion of gestation. Three diets, 0% L-arginine, 0.38% L-arginine and a fortified corn-soybean meal control, were fed to two litter-mate trios from day 30 of gestation until parturition. The experimental diets contained crystalline amino acids as the sole source of nitrogen and provided 12.6% crude protein equivalent. All gilts received 2 kg of diet daily and were housed throughout the 84-day feeding period in metabolism crates. Nitrogen retention tended to increase with advancing pregnancy, but was uninfluenced by dietary treatment. Averaged across all three gestational trimester periods, nitrogen retention was 11.2, 9.7 and 12.0 g/day for the 0% arginine, 0.38% arginine and cor-soybean meal diet, respectively. Urinary excretion of orotic acid was not significantly affected by arginine intake. Moreover, number and weight of pigs at birth and weaning were unaltered by dietary treatment. Thus, it is evident that satisfactory reproductive response can be achieved with gravid swine fed an arginine-free diet during the last 84 days of pregnancy.", "contents": "Nitrogen metabolism and reproductive response of gravid swine fed an arginine-free diet during the last 84 days of gestation. Based upon nitrogen retention and urinary excretion of orotic and citric acid, previous experiments have shown that the gravid gilt does not require a dietary source of arginine during late gestation. This experiment was designed to evaluate effects of feeding an arginine-free diet for a major portion of gestation. Three diets, 0% L-arginine, 0.38% L-arginine and a fortified corn-soybean meal control, were fed to two litter-mate trios from day 30 of gestation until parturition. The experimental diets contained crystalline amino acids as the sole source of nitrogen and provided 12.6% crude protein equivalent. All gilts received 2 kg of diet daily and were housed throughout the 84-day feeding period in metabolism crates. Nitrogen retention tended to increase with advancing pregnancy, but was uninfluenced by dietary treatment. Averaged across all three gestational trimester periods, nitrogen retention was 11.2, 9.7 and 12.0 g/day for the 0% arginine, 0.38% arginine and cor-soybean meal diet, respectively. Urinary excretion of orotic acid was not significantly affected by arginine intake. Moreover, number and weight of pigs at birth and weaning were unaltered by dietary treatment. Thus, it is evident that satisfactory reproductive response can be achieved with gravid swine fed an arginine-free diet during the last 84 days of pregnancy."} {"id": "PMID:1262973", "title": "Metabolism of D- and L-tryptophan in dogs.", "content": "The metabolism of D- and L-[benzene ring-U-14C]tryptophan by dogs was studied. The distribution of label from each isomer in urine, feces, CO2 and various tissues was determined. Thirteen different urinary tryptophan metabolites were isolated by ion exchange cellulose chromatography. D-[14C]Tryptophan was poorly converted to 14CO2 relative to the L-isomer, while giving rise to nearly three times as much urinary 14C as did the L-isomer. The major urinary metabolites of D-tryptophan were unchanged D-tryptophan via indolepyruvic acid appeared to be the major fate of ingested D-tryptophan, with renal excretion of the unchanged D-isomer the next most important fate. The dog apparently utilizes D-tryptophan more efficiently than does the human but much less efficiently than does the rat. The dog appears to be a reasonable animal model for the human in studies of D-tryptophan metabolism.", "contents": "Metabolism of D- and L-tryptophan in dogs. The metabolism of D- and L-[benzene ring-U-14C]tryptophan by dogs was studied. The distribution of label from each isomer in urine, feces, CO2 and various tissues was determined. Thirteen different urinary tryptophan metabolites were isolated by ion exchange cellulose chromatography. D-[14C]Tryptophan was poorly converted to 14CO2 relative to the L-isomer, while giving rise to nearly three times as much urinary 14C as did the L-isomer. The major urinary metabolites of D-tryptophan were unchanged D-tryptophan via indolepyruvic acid appeared to be the major fate of ingested D-tryptophan, with renal excretion of the unchanged D-isomer the next most important fate. The dog apparently utilizes D-tryptophan more efficiently than does the human but much less efficiently than does the rat. The dog appears to be a reasonable animal model for the human in studies of D-tryptophan metabolism."} {"id": "PMID:1262974", "title": "Protein requirements of man: obligatory urinary and fecal nitrogen losses in elderly women.", "content": "Eleven health elderly women, ranging in age from 67 to 91 years, were given an essentially protein-free diet for 8 to 10 days, to determine obligatory urinary and fecal nitrogen losses. Body cell mass (BCM) was calculated from whole body 40K, and basal metabolic rate was determined by indirect calorimetry. Urine was analyzed daily for nitrogen and creatinine, and fecal N was measured in pooled samples. Urinary N output reached a relatively stable-state level by day 6; the average of the last four daily measurements was taken as an estimate of obligatory urinary N loss. The obligatory urinary N was: 24.4 +/- 5.2 mg N/kg body weight; 89.5 +/- 17.1 mg N/kg BCM; 1.44 +/- 0.14 mg N/basal kcal; and 2.11 g N/g creatinine. Obligatory fecal N was 9.8 mg N/kg body weight. Comparison of these results with published data for young adults indicates that obligatory urinary N losses in elderly women are similar to those for young women when expressed per unit body weight but higher than young women and men when expressed per unit creatinine excretion and per unit BCM.", "contents": "Protein requirements of man: obligatory urinary and fecal nitrogen losses in elderly women. Eleven health elderly women, ranging in age from 67 to 91 years, were given an essentially protein-free diet for 8 to 10 days, to determine obligatory urinary and fecal nitrogen losses. Body cell mass (BCM) was calculated from whole body 40K, and basal metabolic rate was determined by indirect calorimetry. Urine was analyzed daily for nitrogen and creatinine, and fecal N was measured in pooled samples. Urinary N output reached a relatively stable-state level by day 6; the average of the last four daily measurements was taken as an estimate of obligatory urinary N loss. The obligatory urinary N was: 24.4 +/- 5.2 mg N/kg body weight; 89.5 +/- 17.1 mg N/kg BCM; 1.44 +/- 0.14 mg N/basal kcal; and 2.11 g N/g creatinine. Obligatory fecal N was 9.8 mg N/kg body weight. Comparison of these results with published data for young adults indicates that obligatory urinary N losses in elderly women are similar to those for young women when expressed per unit body weight but higher than young women and men when expressed per unit creatinine excretion and per unit BCM."} {"id": "PMID:1262975", "title": "Influence of different levels of dietary pyridoxine on certain parameters of developing and mature brains in rats.", "content": "The influence of different levels of dietary pyridoxine-HC1 (1.2, 2.4, 4.8, 9.6, 19.2, 38.4, 76.8 and 153.6 mg/kg diet) fed to dams on certain parameters of developing and mature brain was studied in rats. Brain weights and alanine aminotransferase (ALAT) activities (initial and following in vitro addition of pyridoxal phosphate, PLP) were significantly reduced in brains of 12-day-old pups of dams fed the lowest level of pyridoxine compared to other treatments; in vitro addition of PLP significantly stimulated the activities of glutamic acid decarboxylase (GAD) and ALAT. Vitamin B-6 concentrations in brain were higher for 2-day-old pups of dams fed 38.4 or 76.8 mg vitamin/kg diet and for 12-day-old pups of dams fed 2.4 to 153.6 mg compared to the 1.2 mg groups; at weaning, values were greater in groups fed 76.8 or 153.6 mg compared to the 1.2 mg group. As brain developed during the suckling period, the content of bitamin B-6 and protein increased in all groups, except the 1.2 mg group in which values remained the same. The vitamin and protein content in brain had not reached chemical maturity at weaning as evidenced by greater concentrations of each in brains of dams as compared with values for 21-day-old progeny. As brain developed, ALAT activity increased about 30 times from age 2 to 21 days when activities were similar to those observed in mature brains of dams. Activity of GAD in brain increased about four times from age 12 to 21 days.", "contents": "Influence of different levels of dietary pyridoxine on certain parameters of developing and mature brains in rats. The influence of different levels of dietary pyridoxine-HC1 (1.2, 2.4, 4.8, 9.6, 19.2, 38.4, 76.8 and 153.6 mg/kg diet) fed to dams on certain parameters of developing and mature brain was studied in rats. Brain weights and alanine aminotransferase (ALAT) activities (initial and following in vitro addition of pyridoxal phosphate, PLP) were significantly reduced in brains of 12-day-old pups of dams fed the lowest level of pyridoxine compared to other treatments; in vitro addition of PLP significantly stimulated the activities of glutamic acid decarboxylase (GAD) and ALAT. Vitamin B-6 concentrations in brain were higher for 2-day-old pups of dams fed 38.4 or 76.8 mg vitamin/kg diet and for 12-day-old pups of dams fed 2.4 to 153.6 mg compared to the 1.2 mg groups; at weaning, values were greater in groups fed 76.8 or 153.6 mg compared to the 1.2 mg group. As brain developed during the suckling period, the content of bitamin B-6 and protein increased in all groups, except the 1.2 mg group in which values remained the same. The vitamin and protein content in brain had not reached chemical maturity at weaning as evidenced by greater concentrations of each in brains of dams as compared with values for 21-day-old progeny. As brain developed, ALAT activity increased about 30 times from age 2 to 21 days when activities were similar to those observed in mature brains of dams. Activity of GAD in brain increased about four times from age 12 to 21 days."} {"id": "PMID:1262976", "title": "Influence of dietary zinc on lead toxicity in the rat.", "content": "An investigation of the influence of dietary zinc (8, 35, 200 ppm) on the toxicity of dietary lead (0, 50, 200 ppm) in the young male rat in a seven week period indicated that as dietary zinc increased, the severity of lead toxicity decreased. Evidence included decreased lead concentration in blood, liver, kidneys, and tibias; decreased excretion of urinary delta-aminolevulinic acid; decreased accumulation of free erythrocyte porphyrins; decreased inhibition of kidney delta-aminolevulinic acid dehydrase activity; and a decrease in apparent lead absorption. Infected zinc did not afford protection against lead toxicity. The data indicate that the protective effect of zinc on lead toxicity is largely mediated by an inhibition of lead absorption at the intestinal level.", "contents": "Influence of dietary zinc on lead toxicity in the rat. An investigation of the influence of dietary zinc (8, 35, 200 ppm) on the toxicity of dietary lead (0, 50, 200 ppm) in the young male rat in a seven week period indicated that as dietary zinc increased, the severity of lead toxicity decreased. Evidence included decreased lead concentration in blood, liver, kidneys, and tibias; decreased excretion of urinary delta-aminolevulinic acid; decreased accumulation of free erythrocyte porphyrins; decreased inhibition of kidney delta-aminolevulinic acid dehydrase activity; and a decrease in apparent lead absorption. Infected zinc did not afford protection against lead toxicity. The data indicate that the protective effect of zinc on lead toxicity is largely mediated by an inhibition of lead absorption at the intestinal level."} {"id": "PMID:1262977", "title": "Effect of litter size on weight gain in rats.", "content": "Male rats, placed in litters of 2, 4, 8, 12 and 16 on the first postnatal day, were weighed at 3-day intervals and killed at days 21 or 58. The carcasses were assayed for total protein, DNA and lipid. Animals raised in litters of 16 were significantly smaller than any of the others at all times examined, and their carcasses contained significantly less protein, DNA and lipid. In contrast, animals raised in very small litters exhibited no persistent significant differences in body weight or composition from animals raised in standard-sized litters of 8 or 12.", "contents": "Effect of litter size on weight gain in rats. Male rats, placed in litters of 2, 4, 8, 12 and 16 on the first postnatal day, were weighed at 3-day intervals and killed at days 21 or 58. The carcasses were assayed for total protein, DNA and lipid. Animals raised in litters of 16 were significantly smaller than any of the others at all times examined, and their carcasses contained significantly less protein, DNA and lipid. In contrast, animals raised in very small litters exhibited no persistent significant differences in body weight or composition from animals raised in standard-sized litters of 8 or 12."} {"id": "PMID:1262978", "title": "Effect of selenium on rat growth, growth hormone and diet utilization.", "content": "Female rats were fed a selenium-deficient diet composed of Torula yeast, sucrose, vitamins (including tocopheryl acetate) and minerals from weaning and during breeding, gestation and lactation. The offspring were used to study the effects of selenium on growth, diet utilization and growth hormon status. The Torula yeast diet containing 200 IU dl-alpha-tocopheryl acetate was fed alone or supplemented with 0.025 or 0.1 ppm of selenium as selenite. Rats fed the selenium-supplemented diets grew significently faster and consumed significantly more diet than rats fed the unsupplemented diet. Anterior pituitary weights were lower in selenium-deficient rats, but if expressed per unit of body weight, were similar to pituitary weight of selenium-supplemented animals. Total growth hormone in the anterior pituitary was reduced in selenium-deficient rats. A metabolism study indicated that rats allowed ad libitum access to supplemented diets consumed more diet and obtained more metabolizable energy from the diet than rats fed the deficient diet. It the intake of rats fed the supplemented diets was limited to that of rats allowed ad libitum access to deficient diet, growth of rats was similar. However, metabolizable energy content of the diet increased quadratically and nitrogen digestibility increased linearly as thelevel of selenium increased. Selenium deficiency reduced growth primarily by decreased diet consumption, but also reduced the utilization of energy and nitrogen.", "contents": "Effect of selenium on rat growth, growth hormone and diet utilization. Female rats were fed a selenium-deficient diet composed of Torula yeast, sucrose, vitamins (including tocopheryl acetate) and minerals from weaning and during breeding, gestation and lactation. The offspring were used to study the effects of selenium on growth, diet utilization and growth hormon status. The Torula yeast diet containing 200 IU dl-alpha-tocopheryl acetate was fed alone or supplemented with 0.025 or 0.1 ppm of selenium as selenite. Rats fed the selenium-supplemented diets grew significently faster and consumed significantly more diet than rats fed the unsupplemented diet. Anterior pituitary weights were lower in selenium-deficient rats, but if expressed per unit of body weight, were similar to pituitary weight of selenium-supplemented animals. Total growth hormone in the anterior pituitary was reduced in selenium-deficient rats. A metabolism study indicated that rats allowed ad libitum access to supplemented diets consumed more diet and obtained more metabolizable energy from the diet than rats fed the deficient diet. It the intake of rats fed the supplemented diets was limited to that of rats allowed ad libitum access to deficient diet, growth of rats was similar. However, metabolizable energy content of the diet increased quadratically and nitrogen digestibility increased linearly as thelevel of selenium increased. Selenium deficiency reduced growth primarily by decreased diet consumption, but also reduced the utilization of energy and nitrogen."} {"id": "PMID:1262979", "title": "Gluconeogenesis from lactate in liver of stress-susceptible and stress-resistant pigs.", "content": "In vitro rates of lactate conversion to glucose and oxidation to CO2 were determined in livers of stress-susceptible (SS) and stress-resistant (SR) pigs because we hypothesized that livers of SS pigs had a lower capacity than livers of SR pigs to remove lactate from blood. Stress-susceptibility was determined by reaction to halothane at 7 weeks of age. At approximately 9 weeks of age, pigs were assigned to one of three experimental diets. Pigs weighing 95 kg were slaughtered immediately after stress, and liver samples were obtained. Incorporation of lactate into glucose in liver of SS pigs was 38% of that in SR pigs. Addition of either vitamin C or vitamins C and E plus magnesium oxide and collagen extract to a corn-soy diet did not alter lactate conversion to glucose, but depressed lactate oxidation to CO2. No differences were detected in either activities of lactate dehydrogenase, HAD-malate dehydrogenase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, and glucose-6-phosphatase or concentration of glycogen in livers of SS and SR pigs. Our data indicate that livers of SS pigs possess a lower capacity to incorporate lactate into glucose and to oxidize lactate to CO2; maximal activities of enzymes measured in this study are not the cause of these differences. Reduced capacity of lactate metabolism in livers of SS pigs seems a part of the etiology of the porcine stress syndrome.", "contents": "Gluconeogenesis from lactate in liver of stress-susceptible and stress-resistant pigs. In vitro rates of lactate conversion to glucose and oxidation to CO2 were determined in livers of stress-susceptible (SS) and stress-resistant (SR) pigs because we hypothesized that livers of SS pigs had a lower capacity than livers of SR pigs to remove lactate from blood. Stress-susceptibility was determined by reaction to halothane at 7 weeks of age. At approximately 9 weeks of age, pigs were assigned to one of three experimental diets. Pigs weighing 95 kg were slaughtered immediately after stress, and liver samples were obtained. Incorporation of lactate into glucose in liver of SS pigs was 38% of that in SR pigs. Addition of either vitamin C or vitamins C and E plus magnesium oxide and collagen extract to a corn-soy diet did not alter lactate conversion to glucose, but depressed lactate oxidation to CO2. No differences were detected in either activities of lactate dehydrogenase, HAD-malate dehydrogenase, phosphoenolpyruvate carboxykinase, fructose-1,6-diphosphatase, and glucose-6-phosphatase or concentration of glycogen in livers of SS and SR pigs. Our data indicate that livers of SS pigs possess a lower capacity to incorporate lactate into glucose and to oxidize lactate to CO2; maximal activities of enzymes measured in this study are not the cause of these differences. Reduced capacity of lactate metabolism in livers of SS pigs seems a part of the etiology of the porcine stress syndrome."} {"id": "PMID:1262980", "title": "Effect of spatial frequency on the visibility of unstructured patterns.", "content": "Threshold measurements have been made on random patterns that have been computer filtered to contain only certain spatial frequencies. The dependence of threshold on the spatial-frequency distribution of the energy in the patterns was measured. The results indicate that the visibility of an unstructured pattern is dependent on the spatial-frequency content of the pattern. Near threshold, narrow-band noise is much more visible than wide-band noise. The narrow-band noise visibility is caused by the presence of structure in the pattern, some of which is rotation sensitive. For wider-band noise, the modulation transfer function is circularly symmetric. The visibility of very-wide-band noise near threshold depends only on the luminance variations concentrated within a one-octave spatial-frequency band.", "contents": "Effect of spatial frequency on the visibility of unstructured patterns. Threshold measurements have been made on random patterns that have been computer filtered to contain only certain spatial frequencies. The dependence of threshold on the spatial-frequency distribution of the energy in the patterns was measured. The results indicate that the visibility of an unstructured pattern is dependent on the spatial-frequency content of the pattern. Near threshold, narrow-band noise is much more visible than wide-band noise. The narrow-band noise visibility is caused by the presence of structure in the pattern, some of which is rotation sensitive. For wider-band noise, the modulation transfer function is circularly symmetric. The visibility of very-wide-band noise near threshold depends only on the luminance variations concentrated within a one-octave spatial-frequency band."} {"id": "PMID:1262981", "title": "Interference with line-orientation sensitivity.", "content": "Sensitivity for inclination detection of a foveally seen line is exceedingly high. It is shown that appropriately structured visual stimuli can interfere with the inclination detection threshold, presumably by inhibiting some neural signals before they are channeled to interact with others of their ensemble. The parameters of this inhibition, and by implication those of the sensitivity of the involved neural elements, are outlined: spatial location, time course, movement sensitivity, dichoptic nature, nonrecurrent characteristics, and position rather than orientation dependency.", "contents": "Interference with line-orientation sensitivity. Sensitivity for inclination detection of a foveally seen line is exceedingly high. It is shown that appropriately structured visual stimuli can interfere with the inclination detection threshold, presumably by inhibiting some neural signals before they are channeled to interact with others of their ensemble. The parameters of this inhibition, and by implication those of the sensitivity of the involved neural elements, are outlined: spatial location, time course, movement sensitivity, dichoptic nature, nonrecurrent characteristics, and position rather than orientation dependency."} {"id": "PMID:1262982", "title": "Visual sensitivity of the eye to infrared laser radiation.", "content": "The foveal sensitivity to several near-infrared laser wavelengths was measured. It was found that the eye could respond to radiation at wavelengths at least as far as 1064 nm. A continuous 1064 nm laser source appeared red, but a 1060 nm pulsed laser source appeared green, which suggests the presence of harmonic generation in the retina.", "contents": "Visual sensitivity of the eye to infrared laser radiation. The foveal sensitivity to several near-infrared laser wavelengths was measured. It was found that the eye could respond to radiation at wavelengths at least as far as 1064 nm. A continuous 1064 nm laser source appeared red, but a 1060 nm pulsed laser source appeared green, which suggests the presence of harmonic generation in the retina."} {"id": "PMID:1262983", "title": "On corneal transparency and its loss with swelling.", "content": "The cornea is the clear front covering of the eye through which we see and is composed of collagen fibrils embedded in an optically homogeneous ground substance. It has long been recognized that these fibrils scatter light and that transparency results from interference effects due to an ordering in the spatial arrangement of the fibrils about one another. The nature of this ordering and of its disruption in abnormal corneas is of great current interest. The present study reviews experimental light scattering and electron microscopic evidence relevant to this problem. This evidence suggests that theoretical attempts to model and understand corneal transparency and its loss during swelling, in terms of ultrastructure, must account for a short-ranged ordering of fibrils in normal healthy corneas and for the formation of regions void of fibrils in swollen corneas.", "contents": "On corneal transparency and its loss with swelling. The cornea is the clear front covering of the eye through which we see and is composed of collagen fibrils embedded in an optically homogeneous ground substance. It has long been recognized that these fibrils scatter light and that transparency results from interference effects due to an ordering in the spatial arrangement of the fibrils about one another. The nature of this ordering and of its disruption in abnormal corneas is of great current interest. The present study reviews experimental light scattering and electron microscopic evidence relevant to this problem. This evidence suggests that theoretical attempts to model and understand corneal transparency and its loss during swelling, in terms of ultrastructure, must account for a short-ranged ordering of fibrils in normal healthy corneas and for the formation of regions void of fibrils in swollen corneas."} {"id": "PMID:1263021", "title": "An ultrahistochemical study of the distribution of acid and alkaline phosphatases in placentae from normal and complicated pregnancies.", "content": "The subcellular localisation of acid and alkaline phosphatase has been studied in the trophoblast of placentae from both normal and complicated pregnancies. In placentae from uncomplicated pregnancies the number of trophoblastic acid-phosphatase-containing organelles decreases progressively as gestation proceeds whilst alkaline-phosphatase activity, although abundant at term, could not be demonstrated during the early stages of pregnancy. The acid-phosphatase-containing organelles are of two types; one is a small round body which is probably a lysosome whilst the other is a multivesicular body. The alkaline phosphatase is distributed mainly on the syncytial microvilli and plasma-membrane. It is suggested that the marked lysosomal activity during early pregnancy is related to the architectural refashioning of the placenta during this period and that there are two phosphatase-linked transfer systems in the trophoblast, one dependent upon acid-phosphatase-containing multivesicular bodies and being utilised during early pregnancy and the other reliant upon alkaline phosphatase and dominating during the second half of gestation. In placentae from prolonged pregnancies there is a further decrease in trophoblastic acid phosphatase and, usually, a continuing increase in alkaline-phosphatase activity. In placentae from babies of low birth weight this trend is sometimes reversed and alkaline-phosphatase activity either disappears or its reaction product diffuses throughout the syncytium; this is usually accompanied by a marked increase in the number of acid-phosphatase-containing multivesicular bodies. Placentae from women with pre-eclampsia show no loss of alkaline-phosphatase activity but are characterised by an increased number of lysosomal bodies.", "contents": "An ultrahistochemical study of the distribution of acid and alkaline phosphatases in placentae from normal and complicated pregnancies. The subcellular localisation of acid and alkaline phosphatase has been studied in the trophoblast of placentae from both normal and complicated pregnancies. In placentae from uncomplicated pregnancies the number of trophoblastic acid-phosphatase-containing organelles decreases progressively as gestation proceeds whilst alkaline-phosphatase activity, although abundant at term, could not be demonstrated during the early stages of pregnancy. The acid-phosphatase-containing organelles are of two types; one is a small round body which is probably a lysosome whilst the other is a multivesicular body. The alkaline phosphatase is distributed mainly on the syncytial microvilli and plasma-membrane. It is suggested that the marked lysosomal activity during early pregnancy is related to the architectural refashioning of the placenta during this period and that there are two phosphatase-linked transfer systems in the trophoblast, one dependent upon acid-phosphatase-containing multivesicular bodies and being utilised during early pregnancy and the other reliant upon alkaline phosphatase and dominating during the second half of gestation. In placentae from prolonged pregnancies there is a further decrease in trophoblastic acid phosphatase and, usually, a continuing increase in alkaline-phosphatase activity. In placentae from babies of low birth weight this trend is sometimes reversed and alkaline-phosphatase activity either disappears or its reaction product diffuses throughout the syncytium; this is usually accompanied by a marked increase in the number of acid-phosphatase-containing multivesicular bodies. Placentae from women with pre-eclampsia show no loss of alkaline-phosphatase activity but are characterised by an increased number of lysosomal bodies."} {"id": "PMID:1263022", "title": "The influence of the thymus on multinucleate giant cell formation.", "content": "Glass coverslips were implanted in nude athymic mice and normal controls and the development of multinucleated giant cells on the implant investigated. Although the percentage of the surface area of the coverslip covered by cellular exudate was reduced in older implants (12 days or more) in athymic mice, the proportion of nuclei within syncytia was the same as in normal controls. It is concluded that the multinucleated giant cells in this type of inflammatory lesion are not thymus derived nor is the efficiency of fusion between their precursor mononuclear phagocytes thymus dependent. The number of exuded mononuclear phagocytes on the other hand may be influenced directly or indirectly by the thymus.", "contents": "The influence of the thymus on multinucleate giant cell formation. Glass coverslips were implanted in nude athymic mice and normal controls and the development of multinucleated giant cells on the implant investigated. Although the percentage of the surface area of the coverslip covered by cellular exudate was reduced in older implants (12 days or more) in athymic mice, the proportion of nuclei within syncytia was the same as in normal controls. It is concluded that the multinucleated giant cells in this type of inflammatory lesion are not thymus derived nor is the efficiency of fusion between their precursor mononuclear phagocytes thymus dependent. The number of exuded mononuclear phagocytes on the other hand may be influenced directly or indirectly by the thymus."} {"id": "PMID:1263023", "title": "The effects of pure and micellar solutions of different bile salts on mucosal morphology in rat jejunum in vivo.", "content": "The effects of pure and micellar solutions of different bile salts on mucosal morphology have been investigated in rat jejunum using a closed-loop technique; the effects of an anionic dihydroxy steroid antibiotic, fusidic acid, have also been studied. Mucosal changes were assessed by light-microscopical appearances and quantified by determining surface to volume ratios (c/1h). The unconjugated dihydroxy bile salts, chenodeoxycholate and deoxycholate (DC), produced similar and gross structural changes at concentrations of 2-5 to 5 mM, as judged by mucosal appearances, but not at 1 mM; the unconjugated trihydroxy bile salt cholate and a variety of di- and trihydroxy conjugated salts produced no changes at concentrations of 5 to 20 mM. Fusidate (5 mM) produced similar changes to 5 mM DC. Compared with control values DC (1,2-5 and 5 mM) and fusidate (5 mM) produced highly significant (P less than 0-001) reductions in c/1h ratios. DC-induced damage was completely abolished by mixed micellar solutions, whereas pure micellar solutions provided no protection. These results indicate, (i) a molecular specificity for bile salt-induced mucosal damage, and (ii) that the effects of the unconjugated dihydroxy species on mucosal structure depends not only on their intraluminal concentrations, but also on the relative concentrations of conjugated bile salts and lipids present in the lumen.", "contents": "The effects of pure and micellar solutions of different bile salts on mucosal morphology in rat jejunum in vivo. The effects of pure and micellar solutions of different bile salts on mucosal morphology have been investigated in rat jejunum using a closed-loop technique; the effects of an anionic dihydroxy steroid antibiotic, fusidic acid, have also been studied. Mucosal changes were assessed by light-microscopical appearances and quantified by determining surface to volume ratios (c/1h). The unconjugated dihydroxy bile salts, chenodeoxycholate and deoxycholate (DC), produced similar and gross structural changes at concentrations of 2-5 to 5 mM, as judged by mucosal appearances, but not at 1 mM; the unconjugated trihydroxy bile salt cholate and a variety of di- and trihydroxy conjugated salts produced no changes at concentrations of 5 to 20 mM. Fusidate (5 mM) produced similar changes to 5 mM DC. Compared with control values DC (1,2-5 and 5 mM) and fusidate (5 mM) produced highly significant (P less than 0-001) reductions in c/1h ratios. DC-induced damage was completely abolished by mixed micellar solutions, whereas pure micellar solutions provided no protection. These results indicate, (i) a molecular specificity for bile salt-induced mucosal damage, and (ii) that the effects of the unconjugated dihydroxy species on mucosal structure depends not only on their intraluminal concentrations, but also on the relative concentrations of conjugated bile salts and lipids present in the lumen."} {"id": "PMID:1263024", "title": "Renal damage caused by gentamicin: a study of the effects on renal morphology and urinary enzyme excretion.", "content": "Gentamicin sulphate was administered to male Wistar rats by intramuscular injection at varying dosage and for varying periods. At high dosage (50-100 mg/kg/day) gentamicin causes tubular necrosis. At dosages equivalent to that given to man (5 mg/kg/day) obvious degenerative changes are produced. Similar changes are seen in human tubular epithelium and urine deposits of patients treated with gentamicin. There is increased excretion of urinary enzymes proportional to the degree of tubular damage. The importance of these changes in man is stressed.", "contents": "Renal damage caused by gentamicin: a study of the effects on renal morphology and urinary enzyme excretion. Gentamicin sulphate was administered to male Wistar rats by intramuscular injection at varying dosage and for varying periods. At high dosage (50-100 mg/kg/day) gentamicin causes tubular necrosis. At dosages equivalent to that given to man (5 mg/kg/day) obvious degenerative changes are produced. Similar changes are seen in human tubular epithelium and urine deposits of patients treated with gentamicin. There is increased excretion of urinary enzymes proportional to the degree of tubular damage. The importance of these changes in man is stressed."} {"id": "PMID:1263025", "title": "A population of Pasmodium colmbiense sp. n. in the iguanid lizard, Anolis Auratus.", "content": "Plasmodium colombiense sp. n. is described from 274 naturally infected Anolis auratus from western Colombia. Host blood pictures, parasitemia, parasite structure, infection states, and host population dynamics are correlated. Local epidemics occur, but in contrast to temperate zone species there is little regional synchronization. Active infections occur year-around, being somewhat more common in dry seasons; however, chronic infections predominate. Mature schizonts have 3 to 14, usually 6, 8, or 10 merozoites, reduced to 4 to 6 in chronic infections. Gametocytes are round to oblong, measuring 6 by 5 mu, and the pigment in microgametocytes occurs in a single peripheral vacuole. Parasitemia averaged 2.5% and seldom surpassed 20 to 30%. Infections cause significant anemia, and parasites in active infections are most common in immature erythrocytes. Host response is similar to avian or primate infections, including erythropoiesis, phagocytosis, and interference with parasite growth.", "contents": "A population of Pasmodium colmbiense sp. n. in the iguanid lizard, Anolis Auratus. Plasmodium colombiense sp. n. is described from 274 naturally infected Anolis auratus from western Colombia. Host blood pictures, parasitemia, parasite structure, infection states, and host population dynamics are correlated. Local epidemics occur, but in contrast to temperate zone species there is little regional synchronization. Active infections occur year-around, being somewhat more common in dry seasons; however, chronic infections predominate. Mature schizonts have 3 to 14, usually 6, 8, or 10 merozoites, reduced to 4 to 6 in chronic infections. Gametocytes are round to oblong, measuring 6 by 5 mu, and the pigment in microgametocytes occurs in a single peripheral vacuole. Parasitemia averaged 2.5% and seldom surpassed 20 to 30%. Infections cause significant anemia, and parasites in active infections are most common in immature erythrocytes. Host response is similar to avian or primate infections, including erythropoiesis, phagocytosis, and interference with parasite growth."} {"id": "PMID:1263026", "title": "The effects of selected gases on excystation of coccidian oocysts.", "content": "The mechanism of CO2 action in changing coccidian oocyst wall permeability was indirectly studied by substituting NO, NO2, N2O, H2S, SO2, CH4, NH3, and 8M urea in place of CO2 in an established excystation procedure. Changes in oocyst wall permeability of Eimeria stiedai, E. bovis, and E. tenella were determined by incubation in test gases and cysteine HCl followed by attempted activation of sporozoites by trypsin and bile and staining of intraoocyst components with methylene blue. The gases CH4, NO2, and N2O were negative for all 3 tests, as were SO2, NH3, and 8M urea which, in addition, were toxic to the oocysts. Both H2S and NO were capable of mimicking the action of CO2 and are related chemically to the reducing agent, and thus tend to underscore its importance in excystation. It now appears that the role of CO2 is that of an allosteric effector enhancing the action of the reducing agent.", "contents": "The effects of selected gases on excystation of coccidian oocysts. The mechanism of CO2 action in changing coccidian oocyst wall permeability was indirectly studied by substituting NO, NO2, N2O, H2S, SO2, CH4, NH3, and 8M urea in place of CO2 in an established excystation procedure. Changes in oocyst wall permeability of Eimeria stiedai, E. bovis, and E. tenella were determined by incubation in test gases and cysteine HCl followed by attempted activation of sporozoites by trypsin and bile and staining of intraoocyst components with methylene blue. The gases CH4, NO2, and N2O were negative for all 3 tests, as were SO2, NH3, and 8M urea which, in addition, were toxic to the oocysts. Both H2S and NO were capable of mimicking the action of CO2 and are related chemically to the reducing agent, and thus tend to underscore its importance in excystation. It now appears that the role of CO2 is that of an allosteric effector enhancing the action of the reducing agent."} {"id": "PMID:1263027", "title": "Effects of antiphagocytic agents on penetration of Eimeria magna sporozoites into cultured cells.", "content": "Madin-Darby Bovine Kidney cells were treated with sodium flouride, iodoacetate, and 2-deosyglucose, reagents that block glycolysis, and thus reduce phagocytosis. Sporozoites readily entered cells whose ATP stores were largely depleted. They also entered cells treated with colchicine, colcemid, and vinblastine. These latter agents did not inhibit sporozite motility after 6 hr incubation. Cytochalasin B prevented penetration of cells by inhibiting the motility of sporozoites. This effect was reversible. Warm sporozoites entered cold cells 4 times more radily than cold sporozoites into warm cells. The above findings suggest that phagocytosis is not the mechanism for entry of E. magna sporozoites into cultured cells, but that sporozoite motility is of primary importance.", "contents": "Effects of antiphagocytic agents on penetration of Eimeria magna sporozoites into cultured cells. Madin-Darby Bovine Kidney cells were treated with sodium flouride, iodoacetate, and 2-deosyglucose, reagents that block glycolysis, and thus reduce phagocytosis. Sporozoites readily entered cells whose ATP stores were largely depleted. They also entered cells treated with colchicine, colcemid, and vinblastine. These latter agents did not inhibit sporozite motility after 6 hr incubation. Cytochalasin B prevented penetration of cells by inhibiting the motility of sporozoites. This effect was reversible. Warm sporozoites entered cold cells 4 times more radily than cold sporozoites into warm cells. The above findings suggest that phagocytosis is not the mechanism for entry of E. magna sporozoites into cultured cells, but that sporozoite motility is of primary importance."} {"id": "PMID:1263028", "title": "Eimeria juniataensis sp. n. (Protozoa: Eimeriidae) from the map turtle, Graptemys Geographica, in Pennsylvania.", "content": "Eimeria juniataensis sp. n. is described from the map turtle, Graptemys geographica, in Pennsylvania. The spherical to subspherical oocysts of E. juniataensis are 11.5 to 18.5 mu by 11.5 to 16.5 mu (mean, 13.5 by 12.9mu). The broadly fusiform sporocysts are 7.5 to 10 mu by 4 to 6.5 mu (mean, 8.3 by 5.0mu) and a Stieda body is present. Oocyst and sporocyst residua are present. This is the first report of an eimerian species from Graptemys.", "contents": "Eimeria juniataensis sp. n. (Protozoa: Eimeriidae) from the map turtle, Graptemys Geographica, in Pennsylvania. Eimeria juniataensis sp. n. is described from the map turtle, Graptemys geographica, in Pennsylvania. The spherical to subspherical oocysts of E. juniataensis are 11.5 to 18.5 mu by 11.5 to 16.5 mu (mean, 13.5 by 12.9mu). The broadly fusiform sporocysts are 7.5 to 10 mu by 4 to 6.5 mu (mean, 8.3 by 5.0mu) and a Stieda body is present. Oocyst and sporocyst residua are present. This is the first report of an eimerian species from Graptemys."} {"id": "PMID:1263029", "title": "The fine structure of Schistosoma mansoni sperm (Trematoda: Digenea).", "content": "The sperm of the blood fluke Schistosoma mansoni consist of a bulbous head 8 by 2 mum, with a rounded anterior tip and tapering posterior region, followed by a relatively short flagellum ca. 20 mum long. Electron microscopic observations revealed that these sperm are devoid of an acrosome, while a few undifferentiated mitochondria accumulate at the anterior part of the head. The nucleus appears dense, except for some electron-lucent patches. The flagellum starts at the basal body, posterior and slightly lateral to the nucleus, and the axial complex is of the 9 + 0 type. A layer of microtubules runs longitudinally, just beneath the plasmalemma, from the anterior part of the head to the initial part of the flagellum, where they overlap with the axial complex. It is suggested that this relatively rudimentary type of the S. mansoni sperm is probably related to the low activity required for fertilization.", "contents": "The fine structure of Schistosoma mansoni sperm (Trematoda: Digenea). The sperm of the blood fluke Schistosoma mansoni consist of a bulbous head 8 by 2 mum, with a rounded anterior tip and tapering posterior region, followed by a relatively short flagellum ca. 20 mum long. Electron microscopic observations revealed that these sperm are devoid of an acrosome, while a few undifferentiated mitochondria accumulate at the anterior part of the head. The nucleus appears dense, except for some electron-lucent patches. The flagellum starts at the basal body, posterior and slightly lateral to the nucleus, and the axial complex is of the 9 + 0 type. A layer of microtubules runs longitudinally, just beneath the plasmalemma, from the anterior part of the head to the initial part of the flagellum, where they overlap with the axial complex. It is suggested that this relatively rudimentary type of the S. mansoni sperm is probably related to the low activity required for fertilization."} {"id": "PMID:1263031", "title": "The timing of reproductive cell development and movement in Schistosoma mansoni, S. japonicum, and S. haematobium, using techniques of autoradiography and transplantation.", "content": "Tritiated thymidine was incorporated into gonial and vitelline cells of male and female Schistosoma mansoni, S. japonicum, and S. haematobium after 2 hr of incubation. Spermatogonial cells developed into labeled mature sperm after 6 days of transplantation in all species. Insemination of females was detected on the same day indicating copulation is frequent. Oogonia labeled in the initial incubation matured into primary oocytes after 7 days of transplantation for S. mansoni and S. haematobium and after 6 days in S. japonicum. Cytoplasmic thymidine label was observed after 2-hr incubations in the primary oocytes of all species. Initial label in the vitellaria was scattered and heavy. After 3 days of transplantation, label was considerably diluted and by day 6 was undetectable in vitelline glands. These times for development and movement of reproductive cells are considered to be standards against which the effects of stressful conditions on the reproductive system can be assessed.", "contents": "The timing of reproductive cell development and movement in Schistosoma mansoni, S. japonicum, and S. haematobium, using techniques of autoradiography and transplantation. Tritiated thymidine was incorporated into gonial and vitelline cells of male and female Schistosoma mansoni, S. japonicum, and S. haematobium after 2 hr of incubation. Spermatogonial cells developed into labeled mature sperm after 6 days of transplantation in all species. Insemination of females was detected on the same day indicating copulation is frequent. Oogonia labeled in the initial incubation matured into primary oocytes after 7 days of transplantation for S. mansoni and S. haematobium and after 6 days in S. japonicum. Cytoplasmic thymidine label was observed after 2-hr incubations in the primary oocytes of all species. Initial label in the vitellaria was scattered and heavy. After 3 days of transplantation, label was considerably diluted and by day 6 was undetectable in vitelline glands. These times for development and movement of reproductive cells are considered to be standards against which the effects of stressful conditions on the reproductive system can be assessed."} {"id": "PMID:1263032", "title": "Host-parasite relationships of Fasciola hepatica in the white mouse. VII. effects of anti-worm incubate sera on transferred worms and successful vaccination with a crude incubate antigen.", "content": "Mouse antisera against the 16-day-old worm incubate and sera from 25-day infections in mice debilitated migrating flukes in recipient animals as measured by worm recovery and host mortality. Mouse antisomatic and 100-day infection sera produced no such effects. Host mortality was significantly lower after challenge in mice given one ip immunizing injection of the worm incubate; however, worm recovery was not significantly reduced. Injections at 2, 7, 12, and 24 hr with the worm incubate elaborated over a 24-hr period protected 75% of the mice from infection after challenge, and reduced the worm burden by 83.3%.", "contents": "Host-parasite relationships of Fasciola hepatica in the white mouse. VII. effects of anti-worm incubate sera on transferred worms and successful vaccination with a crude incubate antigen. Mouse antisera against the 16-day-old worm incubate and sera from 25-day infections in mice debilitated migrating flukes in recipient animals as measured by worm recovery and host mortality. Mouse antisomatic and 100-day infection sera produced no such effects. Host mortality was significantly lower after challenge in mice given one ip immunizing injection of the worm incubate; however, worm recovery was not significantly reduced. Injections at 2, 7, 12, and 24 hr with the worm incubate elaborated over a 24-hr period protected 75% of the mice from infection after challenge, and reduced the worm burden by 83.3%."} {"id": "PMID:1263033", "title": "Acanthocephalus tahlequahensis sp. n. (Acanthocephala: Echinorhynchidae) from the the stippled darter, Etheostoma punctulatum (Agassiz), in northeastern Oklahoma.", "content": "Acanthocephalus tahlequahensis sp. n. was recovered from the intestines of 4 species of freshwater fishes, Etheostoma punctulatum, E. spectabile, Nocomis asper, and Notropis pilsbryi, collected in northeastern Oklahoma. The new species is distinguished from all other species of Acanthocephalus, except A. japonicus (Fukui and Morisita 1936) Petrochenko 1956, and A. fluviatilus Paperna 1964, by having smaller proboscis hooks. The length of the proboscis hooks for males is 27 to 38 (33) mum and for females 35 to 46 (42) mum. A. tahlequahensis is smaller than either A. japonicus or A. fluviatilis, and has about half the number of longitudinal rows of proboscis hooks of A. japonicus and half the number of proboscis hooks in each longitudinal row of A. fluviatilus. In addition to having smaller hooks. A. tahlequahensis differs from other species of Acanthocephalus parasitizing North American fishes by its smaller, spindle-shaped trunk and more hooks in each longitudinal row.", "contents": "Acanthocephalus tahlequahensis sp. n. (Acanthocephala: Echinorhynchidae) from the the stippled darter, Etheostoma punctulatum (Agassiz), in northeastern Oklahoma. Acanthocephalus tahlequahensis sp. n. was recovered from the intestines of 4 species of freshwater fishes, Etheostoma punctulatum, E. spectabile, Nocomis asper, and Notropis pilsbryi, collected in northeastern Oklahoma. The new species is distinguished from all other species of Acanthocephalus, except A. japonicus (Fukui and Morisita 1936) Petrochenko 1956, and A. fluviatilus Paperna 1964, by having smaller proboscis hooks. The length of the proboscis hooks for males is 27 to 38 (33) mum and for females 35 to 46 (42) mum. A. tahlequahensis is smaller than either A. japonicus or A. fluviatilis, and has about half the number of longitudinal rows of proboscis hooks of A. japonicus and half the number of proboscis hooks in each longitudinal row of A. fluviatilus. In addition to having smaller hooks. A. tahlequahensis differs from other species of Acanthocephalus parasitizing North American fishes by its smaller, spindle-shaped trunk and more hooks in each longitudinal row."} {"id": "PMID:1263034", "title": "Influence of potassium ion and osomtic pressure on development of Haemonchus contortus in vitro.", "content": "Development of infective larvae of Haemonchus contortus to the fourth stage in vitro was impaired if the concentration of potassium ion in the medium was 0.26 mM or less. At or below 0.015 mM, development was almost completely stopped. High concentrations of potassium, in solutions with a ratio of sodium to potassium from 150 down to 1.3, were all equally favorable for development, but solutions composed only of salts of potassium were unfavorable. Development was impaired by osmotic pressures below 200 mosm/kg or above 350 mosm/kg and ecdysis was arrested by high but not by low osmotic pressures.", "contents": "Influence of potassium ion and osomtic pressure on development of Haemonchus contortus in vitro. Development of infective larvae of Haemonchus contortus to the fourth stage in vitro was impaired if the concentration of potassium ion in the medium was 0.26 mM or less. At or below 0.015 mM, development was almost completely stopped. High concentrations of potassium, in solutions with a ratio of sodium to potassium from 150 down to 1.3, were all equally favorable for development, but solutions composed only of salts of potassium were unfavorable. Development was impaired by osmotic pressures below 200 mosm/kg or above 350 mosm/kg and ecdysis was arrested by high but not by low osmotic pressures."} {"id": "PMID:1263035", "title": "Effect of desiccation on the survival of infective Haemonchus contorus larvae under laboratory conditions.", "content": "When stored in water at 4 and 20 C, respectively, 42 and 36% of free 3rd-stage, infective larvae of Haemonchus contortus were alive after 256 days. When stored at -95 C, 73% of the free, desiccated larvae died during the 1st half hour and 80% during the 1st half day; thereafter no more died for 255 days, the duration of the experiment. Desiccation protected the larvae against death on storage at temperature below freezing, but it was harmful at temperatures above freezing. H. contortus larvae do not withstand a single episode of desiccation as well as Trichostrongylus colubrformis larvae.", "contents": "Effect of desiccation on the survival of infective Haemonchus contorus larvae under laboratory conditions. When stored in water at 4 and 20 C, respectively, 42 and 36% of free 3rd-stage, infective larvae of Haemonchus contortus were alive after 256 days. When stored at -95 C, 73% of the free, desiccated larvae died during the 1st half hour and 80% during the 1st half day; thereafter no more died for 255 days, the duration of the experiment. Desiccation protected the larvae against death on storage at temperature below freezing, but it was harmful at temperatures above freezing. H. contortus larvae do not withstand a single episode of desiccation as well as Trichostrongylus colubrformis larvae."} {"id": "PMID:1263036", "title": "Probstamyria gombensis sp. n. (Nematoda: Atractidae) from the chimpanzee.", "content": "The worm is distinguished by the presence of both unequal spicules and a gubernaculum in the male and also the elongated nipplelike tip of the right spicule. P. gombensis was found to be a common parasite within a troop of feral chimpanzees living in Gombe National Park, Tanzania.", "contents": "Probstamyria gombensis sp. n. (Nematoda: Atractidae) from the chimpanzee. The worm is distinguished by the presence of both unequal spicules and a gubernaculum in the male and also the elongated nipplelike tip of the right spicule. P. gombensis was found to be a common parasite within a troop of feral chimpanzees living in Gombe National Park, Tanzania."} {"id": "PMID:1263037", "title": "Scanning electron microscopy of the lip denticiles of Ascaris suum adults of known ages.", "content": "Purebred Hampshire pigs, farrowed and maintained under conditions precluding extraneous helminth infection, were exposed to a single dose of 10,000 Ascaris suum infective eggs. The pigs were killed at intervals of 28, 41, 55, 86, 115, 145, 175, and 206 days after infection. At necropsy, no gross lesions were found in the lungs or livers of infected pigs. The worms were recovered from the small intestine, identified, counted, and fixed. The heads were excised, critical point dried, mounted en face, and examined by scanning electron microscopy. Worms 28 to 115 days old had unworn denticles that were triangular when viewed laterally but blunt when viewed tangentially. Wearing of the denticles was observed first with 145-day-old worms; wearing increased with age both in numbers of denticles affected and in degree of wear so that by 206 days after inoculation, almost all denticles in the center of the lip were worn. Worn denticles appear truncated when viewed from any angle. The denticles outside the central area were not affected by wear. The size of the denticles varies not only between specimens of the same age, but also on each specimen. However, average denticle size is directly related to the size and, accordingly, to the age of the worm. External to each denticle is a corresponding depression that we have called the denticular groove. One 28-day-old specimen had some extra denticles aligned irregularly along the lip; this irregularity gave the appearance of a double row. The denticles of the two subventral lips are similar to those of the dorsal and are equally affected by wear. There was no detectable difference in denticles of male and female worms. Since wear can now be specifically correlated with age, we conclude that the denticles are functional and become worn through use. Consequently, adult A. suum may be an even more injurious pathogen than heretofore supposed.", "contents": "Scanning electron microscopy of the lip denticiles of Ascaris suum adults of known ages. Purebred Hampshire pigs, farrowed and maintained under conditions precluding extraneous helminth infection, were exposed to a single dose of 10,000 Ascaris suum infective eggs. The pigs were killed at intervals of 28, 41, 55, 86, 115, 145, 175, and 206 days after infection. At necropsy, no gross lesions were found in the lungs or livers of infected pigs. The worms were recovered from the small intestine, identified, counted, and fixed. The heads were excised, critical point dried, mounted en face, and examined by scanning electron microscopy. Worms 28 to 115 days old had unworn denticles that were triangular when viewed laterally but blunt when viewed tangentially. Wearing of the denticles was observed first with 145-day-old worms; wearing increased with age both in numbers of denticles affected and in degree of wear so that by 206 days after inoculation, almost all denticles in the center of the lip were worn. Worn denticles appear truncated when viewed from any angle. The denticles outside the central area were not affected by wear. The size of the denticles varies not only between specimens of the same age, but also on each specimen. However, average denticle size is directly related to the size and, accordingly, to the age of the worm. External to each denticle is a corresponding depression that we have called the denticular groove. One 28-day-old specimen had some extra denticles aligned irregularly along the lip; this irregularity gave the appearance of a double row. The denticles of the two subventral lips are similar to those of the dorsal and are equally affected by wear. There was no detectable difference in denticles of male and female worms. Since wear can now be specifically correlated with age, we conclude that the denticles are functional and become worn through use. Consequently, adult A. suum may be an even more injurious pathogen than heretofore supposed."} {"id": "PMID:1263038", "title": "Didelphostrongylus hayesi gen. et sp. n. (Metastrogyloidea: Filaroididae) from the opossum, Didelphis marsupialis.", "content": "Didelphostrongylus hayesi gen. et sp. n. from the opossum, Didelphis marsupialis, is distinguished from other genera of the Angoistrongylinae by the structure of the dorsal and lateral rays, complex gubernaculum, and ovoviviparity. Third-stage larvae developed in Mesodon perigraptus and Triodopsis albolabris. The prepatent period was 22 days in experimentally infected opossums.", "contents": "Didelphostrongylus hayesi gen. et sp. n. (Metastrogyloidea: Filaroididae) from the opossum, Didelphis marsupialis. Didelphostrongylus hayesi gen. et sp. n. from the opossum, Didelphis marsupialis, is distinguished from other genera of the Angoistrongylinae by the structure of the dorsal and lateral rays, complex gubernaculum, and ovoviviparity. Third-stage larvae developed in Mesodon perigraptus and Triodopsis albolabris. The prepatent period was 22 days in experimentally infected opossums."} {"id": "PMID:1263039", "title": "Natural infection of Aedes trivittatus (COQ) with Dirofilaria immitis in central Iowa.", "content": "Juveniles identified as Dirofilaria immitis were recovered from Aedes trivittatus and Anopheles punctipennis collected CO2-baited CDC light traps in Ames, Iowa, during 10 days in July and August 1975. Ae. trivittatus composed 58.7% of the mosquitoes collected, and D. immitis was recovered from 18 of 393 (4.6%) dissected and from 7 of 31 pools (911 mosquitoes; 0.77%). Approximately 1.0% of the Ae. trivittatus collected harbored infective-stage juveniles, and as many as 27 were recovered from a single mosquito. This is the first report of Ae. trivittatus supporting the development of D. immitis. An. punctipennis was the only other species infected, with 2 of 468 harboring first-stage juveniles. The data suggest that Ae. trivittatus probably is the principal vector of D. immitis in central Iowa.", "contents": "Natural infection of Aedes trivittatus (COQ) with Dirofilaria immitis in central Iowa. Juveniles identified as Dirofilaria immitis were recovered from Aedes trivittatus and Anopheles punctipennis collected CO2-baited CDC light traps in Ames, Iowa, during 10 days in July and August 1975. Ae. trivittatus composed 58.7% of the mosquitoes collected, and D. immitis was recovered from 18 of 393 (4.6%) dissected and from 7 of 31 pools (911 mosquitoes; 0.77%). Approximately 1.0% of the Ae. trivittatus collected harbored infective-stage juveniles, and as many as 27 were recovered from a single mosquito. This is the first report of Ae. trivittatus supporting the development of D. immitis. An. punctipennis was the only other species infected, with 2 of 468 harboring first-stage juveniles. The data suggest that Ae. trivittatus probably is the principal vector of D. immitis in central Iowa."} {"id": "PMID:1263040", "title": "Efficacy of p-Toluoyl chloride phenylhydrazone against gastrointestinal helminths in ovines.", "content": "A new anthelmintic candidate, p-toluoyl chloride phenlylhydrazone, was administered to lambs in a paste formulation. The efficacy of this drug was determined at dose rates of 20, 30, 40, and 50 mg of active ingredient per kilogram of body weight. Helminths expelled by these dosages included Haemonchus contortus, Ostertagia circumcicta, Trichostrongylus colubriformis, T. axei, Nematodirus filicollis, Cooperia curticei, Strongyloides papillosus, Oesophagostomum columbianum, Bunostomum trigoncephalum, Chabertia ovina, Moniezia expansa, and M. benedeni.", "contents": "Efficacy of p-Toluoyl chloride phenylhydrazone against gastrointestinal helminths in ovines. A new anthelmintic candidate, p-toluoyl chloride phenlylhydrazone, was administered to lambs in a paste formulation. The efficacy of this drug was determined at dose rates of 20, 30, 40, and 50 mg of active ingredient per kilogram of body weight. Helminths expelled by these dosages included Haemonchus contortus, Ostertagia circumcicta, Trichostrongylus colubriformis, T. axei, Nematodirus filicollis, Cooperia curticei, Strongyloides papillosus, Oesophagostomum columbianum, Bunostomum trigoncephalum, Chabertia ovina, Moniezia expansa, and M. benedeni."} {"id": "PMID:1263041", "title": "Studies on resistance in snails. 4. Induction of ventricular capsules and changes in the amebocyte-producing organ during sensitization of Biomphalaria glabrata snails.", "content": "Formation of an amebocyte aggregate in the ventricular cavity of Biomphalaria glabrata can be induced 30 hr or more after a single infection by irradiated or (less frequently) by normal Echinostoma lindoense miracidia. The resulting amebocyte mass frequently encapsulated and destroyed the developing E. lindoense sporocysts within the ventricle. The constituent amebocytes of the capsule correspond in vitro and by staining characteristics to circulating amebocytes of uninfected snails, but with additional inclusion bodies, increased mucopolysaccharide, acid phosphatases, and lipid-positive staining reactions. Mitotic activity, rapid growth, and later regression of the amebocyte-producing organ (located between the posterior mantle epithelium and anterior pericardial endothelium) follow the growth and regression sequence of the ventricular capsule. Though peripheral foci of secondary amebocyte production have been found and were previously known, the amebocyte-producing organ appears to be the primary amebocyte source responsible for the snails' rapid intraventricular sporocyst encapsulation.", "contents": "Studies on resistance in snails. 4. Induction of ventricular capsules and changes in the amebocyte-producing organ during sensitization of Biomphalaria glabrata snails. Formation of an amebocyte aggregate in the ventricular cavity of Biomphalaria glabrata can be induced 30 hr or more after a single infection by irradiated or (less frequently) by normal Echinostoma lindoense miracidia. The resulting amebocyte mass frequently encapsulated and destroyed the developing E. lindoense sporocysts within the ventricle. The constituent amebocytes of the capsule correspond in vitro and by staining characteristics to circulating amebocytes of uninfected snails, but with additional inclusion bodies, increased mucopolysaccharide, acid phosphatases, and lipid-positive staining reactions. Mitotic activity, rapid growth, and later regression of the amebocyte-producing organ (located between the posterior mantle epithelium and anterior pericardial endothelium) follow the growth and regression sequence of the ventricular capsule. Though peripheral foci of secondary amebocyte production have been found and were previously known, the amebocyte-producing organ appears to be the primary amebocyte source responsible for the snails' rapid intraventricular sporocyst encapsulation."} {"id": "PMID:1263042", "title": "Studies on resistance in snails. 5. Tissue reactions to Echinostoma lincloense in naturally resistant Biomphalaria glabrata.", "content": "Laboratory-raised juvenile albino Biomphalaria glabrata snails show a wide range of natural resistance to a single infection with 50 or 100 miracidia of Echinostoma lindoense. In the most resistant snails all sporocysts are destroyed in peripheral tissues soon after miracidial penetration. In less resistant snails some sporocysts reach the heart where they are encapsulated. In fully susceptible snails, all sporocysts rapidly migrate to the heart, where they mature and continue to develop. The greater part of our B. glabrata colony consists of snails in which sporocysts reaching the heart will survive, but in which a varying number of sporocysts will be destroyed in the tissues. These snails are usually considered susceptible, as they do become infected. Tissue reactions induced by sporocysts following a single infection in naturally resistant snails are similar to reactions in snails with an acquired resistance. In fully susceptible snails, the amebocyte-producing organ remains small and inactive. It is slightly to moderately stimulated in partially resistant snails in which destruction of sporocysts occurs in the tissues and surviving larvae are found in the ventricle. In snails in which amebocyte aggregates or capsules develop in the ventricle, the organ becomes markedly enlarged. Migration of sporocysts in the snail appears not to be continuous, as periodic rests seem to occur. Migration follows intrusion of the sporocyst through the tissues, induced by bodily distension and contraction, and then proceeds within the arteries against the blood flow, passing from one endothelial attachment site to another, possibly aided by negative pressure during ventricular diastole.", "contents": "Studies on resistance in snails. 5. Tissue reactions to Echinostoma lincloense in naturally resistant Biomphalaria glabrata. Laboratory-raised juvenile albino Biomphalaria glabrata snails show a wide range of natural resistance to a single infection with 50 or 100 miracidia of Echinostoma lindoense. In the most resistant snails all sporocysts are destroyed in peripheral tissues soon after miracidial penetration. In less resistant snails some sporocysts reach the heart where they are encapsulated. In fully susceptible snails, all sporocysts rapidly migrate to the heart, where they mature and continue to develop. The greater part of our B. glabrata colony consists of snails in which sporocysts reaching the heart will survive, but in which a varying number of sporocysts will be destroyed in the tissues. These snails are usually considered susceptible, as they do become infected. Tissue reactions induced by sporocysts following a single infection in naturally resistant snails are similar to reactions in snails with an acquired resistance. In fully susceptible snails, the amebocyte-producing organ remains small and inactive. It is slightly to moderately stimulated in partially resistant snails in which destruction of sporocysts occurs in the tissues and surviving larvae are found in the ventricle. In snails in which amebocyte aggregates or capsules develop in the ventricle, the organ becomes markedly enlarged. Migration of sporocysts in the snail appears not to be continuous, as periodic rests seem to occur. Migration follows intrusion of the sporocyst through the tissues, induced by bodily distension and contraction, and then proceeds within the arteries against the blood flow, passing from one endothelial attachment site to another, possibly aided by negative pressure during ventricular diastole."} {"id": "PMID:1263043", "title": "Studies on resistance in snails. 6. Escape of Echinostoma lindoense sporocysts from encapsulation in the snail heart and subsequent loss of the host's ability to resist infection by the same parasite.", "content": "Formation of amebocyte aggregates in the ventricular cavity of Biomphalaria glabrata, induced by developing sporocysts of Echinostoma lindoense, does not always result in destruction of the parasites, as the sporocysts occasionally escape encapsulation in the heart. When this occurs, a remarkable loss of protective capacity follows and the host snails become highly susceptible to reinfection with the same species--even more so than in control susceptible snails exposed for the first time. Although the amebocyte-producing organ is considerably enlarged after a first infection and shows numerous mitoses, the amebocytes produced by snails harboring an \"escaped\" infection in the heart appear unable to attack the parasites of the first or of the second exposure. Instead, the amebocytes produced accumulate in the loose connective tissues between the liver lobuli, where early developmental stages of the parasites do not occur. These amebocytes apparently have lost their ability to recognize the parasites as foreign.", "contents": "Studies on resistance in snails. 6. Escape of Echinostoma lindoense sporocysts from encapsulation in the snail heart and subsequent loss of the host's ability to resist infection by the same parasite. Formation of amebocyte aggregates in the ventricular cavity of Biomphalaria glabrata, induced by developing sporocysts of Echinostoma lindoense, does not always result in destruction of the parasites, as the sporocysts occasionally escape encapsulation in the heart. When this occurs, a remarkable loss of protective capacity follows and the host snails become highly susceptible to reinfection with the same species--even more so than in control susceptible snails exposed for the first time. Although the amebocyte-producing organ is considerably enlarged after a first infection and shows numerous mitoses, the amebocytes produced by snails harboring an \"escaped\" infection in the heart appear unable to attack the parasites of the first or of the second exposure. Instead, the amebocytes produced accumulate in the loose connective tissues between the liver lobuli, where early developmental stages of the parasites do not occur. These amebocytes apparently have lost their ability to recognize the parasites as foreign."} {"id": "PMID:1263044", "title": "Resistance to Boophilus microplus (Canestrini) in genetically different types of calves in early life.", "content": "Tick resistance and blood composition were studied in British (1/2 Shorthorn x 1/2 Hereford) and zebu (1/2 Brahman x 1/2 British) calves from birth to 33 days of age in a tropical grazing area in which B. microplus is endemic. Calves of the 2 breeds were either naturally infested or were, in addition, artificially infested with 5,000 larvae at 2 and 9 days of age. Total numbers of mature female ticks carried from either type of infestation were significantly lower (P less than 0.01) on zebu than on British calves. In the artificially infested calves of both breeds, the total number of ticks maturing between 20 to 26 days of age was significantly higher (P less than 0.01) than the number maturing between 27 to 33 days of age emphasizing that a major component of resistance is acquired. However, in the naturally infested calves, breed differences in the numbers of ticks maturing during these 2 periods suggested the presence of genetic differences in innate resistance. Within breeds, total tick numbers carried during the study were negatively correlated with calf weight gain and with the concentrations of serum albumin, total protein, and cholesterol.", "contents": "Resistance to Boophilus microplus (Canestrini) in genetically different types of calves in early life. Tick resistance and blood composition were studied in British (1/2 Shorthorn x 1/2 Hereford) and zebu (1/2 Brahman x 1/2 British) calves from birth to 33 days of age in a tropical grazing area in which B. microplus is endemic. Calves of the 2 breeds were either naturally infested or were, in addition, artificially infested with 5,000 larvae at 2 and 9 days of age. Total numbers of mature female ticks carried from either type of infestation were significantly lower (P less than 0.01) on zebu than on British calves. In the artificially infested calves of both breeds, the total number of ticks maturing between 20 to 26 days of age was significantly higher (P less than 0.01) than the number maturing between 27 to 33 days of age emphasizing that a major component of resistance is acquired. However, in the naturally infested calves, breed differences in the numbers of ticks maturing during these 2 periods suggested the presence of genetic differences in innate resistance. Within breeds, total tick numbers carried during the study were negatively correlated with calf weight gain and with the concentrations of serum albumin, total protein, and cholesterol."} {"id": "PMID:1263045", "title": "A new observation on spermateleosis in ticks.", "content": "The first phase of spermiogenesis in argasid and ixodid ticks is described. The inner core of the spermatid passes through the outer sheath so that speriogenesis is permitted to follow its course. The outer sheath is not ruptured in the process, but a well-defined operculum opens to let the inner core through. The opening of the operculum is a clear-cut indication of the beginning of spermiogenesis. In the examined species speriogenesis begins in Argasidae when the male transfers the spermatophore to the female genital opening, whereas in Ixodidae it starts only after the endospermatophore has reached the female genital tract.", "contents": "A new observation on spermateleosis in ticks. The first phase of spermiogenesis in argasid and ixodid ticks is described. The inner core of the spermatid passes through the outer sheath so that speriogenesis is permitted to follow its course. The outer sheath is not ruptured in the process, but a well-defined operculum opens to let the inner core through. The opening of the operculum is a clear-cut indication of the beginning of spermiogenesis. In the examined species speriogenesis begins in Argasidae when the male transfers the spermatophore to the female genital opening, whereas in Ixodidae it starts only after the endospermatophore has reached the female genital tract."} {"id": "PMID:1263052", "title": "The development of anorectal continence and its significance in the diagnosiso of Hirschsprung's disease.", "content": "The development of the anorectal continence reaction was studied in a series of 138 electromanometric recordings performed in 62 newborn and six premature infants. Forty-five babies were observed in a longitudinal study. In 11% an internal sphincter relaxation was observed at the time of birth. The same reflex was present in about 50% after the third day and in all infants after the 12th day of life. The development of a rectal continence reaction depends on an intact internal sphincter relaxation. The puborectalis muscle, is fully functional at birth. On the basis of these findings electromanometric recordings can be used to exclude aganglionic megacolon as early as the first day of life. An absent internal sphincter relaxation reflex, is diagnostic only after the 12th day of life.", "contents": "The development of anorectal continence and its significance in the diagnosiso of Hirschsprung's disease. The development of the anorectal continence reaction was studied in a series of 138 electromanometric recordings performed in 62 newborn and six premature infants. Forty-five babies were observed in a longitudinal study. In 11% an internal sphincter relaxation was observed at the time of birth. The same reflex was present in about 50% after the third day and in all infants after the 12th day of life. The development of a rectal continence reaction depends on an intact internal sphincter relaxation. The puborectalis muscle, is fully functional at birth. On the basis of these findings electromanometric recordings can be used to exclude aganglionic megacolon as early as the first day of life. An absent internal sphincter relaxation reflex, is diagnostic only after the 12th day of life."} {"id": "PMID:1263053", "title": "Manometric assessment of continence after surgery for imperforate anus.", "content": "Of 49 children with imperforate anus, 23 underwent an abdominoperineal procedure for a high and seven for a low maliformation, 17 had a perineoplasty for a low and two for a high malformation. In each subject, rectal and anal sphincteric resting pressures were studied at least 1 yr after surgery. Of 30 subjects who had undergone an abdominoperineal procedure, eight were continent in contrast to 15 out of 19 patients who had had a perineoplasty (p less than 0.001). In patients who had undergone an abdominoperineal procedure, the rectal motility was of the colonic type, with waves of higher amplitude and lower frequency (p less than 0.01) than in the normal rectum in 23 cases and in most of these, peristalsis was recorded down to the anal margin. Incontinence was most frequently associated with abnormally short anal resistance, low anal pressure, reduced sensibility, weak voluntary contraction and absence of rectoanal inhibitory reflex. In the group of patients who underwent perineoplasty, continence was associated with normal mechanical parameters and normal physiologic behavior of the anal sphincter.", "contents": "Manometric assessment of continence after surgery for imperforate anus. Of 49 children with imperforate anus, 23 underwent an abdominoperineal procedure for a high and seven for a low maliformation, 17 had a perineoplasty for a low and two for a high malformation. In each subject, rectal and anal sphincteric resting pressures were studied at least 1 yr after surgery. Of 30 subjects who had undergone an abdominoperineal procedure, eight were continent in contrast to 15 out of 19 patients who had had a perineoplasty (p less than 0.001). In patients who had undergone an abdominoperineal procedure, the rectal motility was of the colonic type, with waves of higher amplitude and lower frequency (p less than 0.01) than in the normal rectum in 23 cases and in most of these, peristalsis was recorded down to the anal margin. Incontinence was most frequently associated with abnormally short anal resistance, low anal pressure, reduced sensibility, weak voluntary contraction and absence of rectoanal inhibitory reflex. In the group of patients who underwent perineoplasty, continence was associated with normal mechanical parameters and normal physiologic behavior of the anal sphincter."} {"id": "PMID:1263054", "title": "Infantile hypertrophic pyloric stenosis related to ingestion of erythromycine estolate: A report of five cases.", "content": "During a 1-yr period an increased incidence of hypertrophic PS was noted in a closed referral population. These patients demonstrated a temporal relationship between the ingestion of EE and the development of PS. A sequence of events from pylorospasm to pyloric tumors was suggested from the data.", "contents": "Infantile hypertrophic pyloric stenosis related to ingestion of erythromycine estolate: A report of five cases. During a 1-yr period an increased incidence of hypertrophic PS was noted in a closed referral population. These patients demonstrated a temporal relationship between the ingestion of EE and the development of PS. A sequence of events from pylorospasm to pyloric tumors was suggested from the data."} {"id": "PMID:1263055", "title": "Congenital pyloric atresia: Report of a familial occurrence.", "content": "Fifty-nine cases of congenital pyloric atresia have been previously reported. A familial occurrence has been described in thirteen infants in six families. This report adds two cases.", "contents": "Congenital pyloric atresia: Report of a familial occurrence. Fifty-nine cases of congenital pyloric atresia have been previously reported. A familial occurrence has been described in thirteen infants in six families. This report adds two cases."} {"id": "PMID:1263056", "title": "Malignant hyperpyrexia during anesthesia in childhood.", "content": "Malignant hyperpyrexia is a highly lethal complication of general anesthesia. It occurs with sufficient frequency, particularly in children and young adults, to justify use of continuous temperature monitoring during adminnstration of general anesthesia. Fever may be a late manifestation of the malignant hyperpyrexia syndrome, and it is important to be aware of the early signs. Prompt recognition and aggressive management should lower the high mortality known to occur with this complication. Family members should be screened for CPK elevations to determine possible susceptibility to malignant hyperpyrexia. Two case reports illustrate these points of diagnosis and management.", "contents": "Malignant hyperpyrexia during anesthesia in childhood. Malignant hyperpyrexia is a highly lethal complication of general anesthesia. It occurs with sufficient frequency, particularly in children and young adults, to justify use of continuous temperature monitoring during adminnstration of general anesthesia. Fever may be a late manifestation of the malignant hyperpyrexia syndrome, and it is important to be aware of the early signs. Prompt recognition and aggressive management should lower the high mortality known to occur with this complication. Family members should be screened for CPK elevations to determine possible susceptibility to malignant hyperpyrexia. Two case reports illustrate these points of diagnosis and management."} {"id": "PMID:1263057", "title": "Intestinal obstruction in Nigerian children.", "content": "A 10-yr review of acute intestinal obstruction in 280 Nigerian children reveals that the condition is the major cause of surgical emergencies in Nigerian children, as in children of other developing countries. These are significant differences of pediatric intestinal obstruction in developing countries, as compared with the pattern in other parts of the world. Intussuscaption was the leading cause followed by incarcerated or strangulated hernia. Lateness in presentation was common, with a resulting high morbidity and prolonged hospital stay. The overall mortality was 16%, but mortality of 33% was recorded in the neonatal group.", "contents": "Intestinal obstruction in Nigerian children. A 10-yr review of acute intestinal obstruction in 280 Nigerian children reveals that the condition is the major cause of surgical emergencies in Nigerian children, as in children of other developing countries. These are significant differences of pediatric intestinal obstruction in developing countries, as compared with the pattern in other parts of the world. Intussuscaption was the leading cause followed by incarcerated or strangulated hernia. Lateness in presentation was common, with a resulting high morbidity and prolonged hospital stay. The overall mortality was 16%, but mortality of 33% was recorded in the neonatal group."} {"id": "PMID:1263058", "title": "The simultaneous occurrence of paraduodenal and paracecal herniae presenting with volvulus of the intervening bowel.", "content": "A very rare coincidence of paraduodenal and paracecal hernia with volvulus of the intervening small intestine is reported. The unusual anatomical set up predising to volvulus of a large loop of small bowel has been described. Restoration of normal anatomy was made possible by the application of principles of treatment of internal herniae.", "contents": "The simultaneous occurrence of paraduodenal and paracecal herniae presenting with volvulus of the intervening bowel. A very rare coincidence of paraduodenal and paracecal hernia with volvulus of the intervening small intestine is reported. The unusual anatomical set up predising to volvulus of a large loop of small bowel has been described. Restoration of normal anatomy was made possible by the application of principles of treatment of internal herniae."} {"id": "PMID:1263059", "title": "Leading points in childhood intussusception.", "content": "Children whose intussusception is caused by a specific pathologic lesion are harder to diagnose and have a higher morbidity than those with the idiopathic variety. We have collected and analyzed 31 such cases found in a series of over 500 intussusceptions. The average age of these children was greater than is usually found in most cases, and the duration of the signs and symptoms was also longer than is usually seen. Almost 50% presented with a picture of advanced small bowel obstruction. Fewer barium enemas were done (50%) and none was successful in reducing the intussusception. There was a higher number of ileo-ideal intussusceptions in this group. The commonest leading points were Meckel's diverticula, polyps, and duplications. All patients with leading points required operation; three-fourths had a bowel resection performed. This study of 569 cases suggests that older children with intussusception and children with recurrent intussusception do not necessarily have leading points causing their intussusceptions.", "contents": "Leading points in childhood intussusception. Children whose intussusception is caused by a specific pathologic lesion are harder to diagnose and have a higher morbidity than those with the idiopathic variety. We have collected and analyzed 31 such cases found in a series of over 500 intussusceptions. The average age of these children was greater than is usually found in most cases, and the duration of the signs and symptoms was also longer than is usually seen. Almost 50% presented with a picture of advanced small bowel obstruction. Fewer barium enemas were done (50%) and none was successful in reducing the intussusception. There was a higher number of ileo-ideal intussusceptions in this group. The commonest leading points were Meckel's diverticula, polyps, and duplications. All patients with leading points required operation; three-fourths had a bowel resection performed. This study of 569 cases suggests that older children with intussusception and children with recurrent intussusception do not necessarily have leading points causing their intussusceptions."} {"id": "PMID:1263060", "title": "Occult appendiceal abscess complicating cystic fibrosis.", "content": "Three case histories illustrate the diagnostic dilemma encountered whenever a patient with CF who is receiving antibiotics is evaluated for abdominal pain. Although acute appendicitis with perforation and abscess formation is not a common complication of CF, it occurs more frequently than is generally appreciated. The large number of abdominal situations in CF which can cause pain confused with but not typical of acute appendicitis. The true underlying condition is further masked by the concurrent use of antibiotics for pulmonary infection. A higher index of suspicion is needed to rule out acute appendicitis in a patient with cystic fibrosis and abdominal pain. A greater awaremess of the possibility of occult appendiceal abscess may help to avoid this complication.", "contents": "Occult appendiceal abscess complicating cystic fibrosis. Three case histories illustrate the diagnostic dilemma encountered whenever a patient with CF who is receiving antibiotics is evaluated for abdominal pain. Although acute appendicitis with perforation and abscess formation is not a common complication of CF, it occurs more frequently than is generally appreciated. The large number of abdominal situations in CF which can cause pain confused with but not typical of acute appendicitis. The true underlying condition is further masked by the concurrent use of antibiotics for pulmonary infection. A higher index of suspicion is needed to rule out acute appendicitis in a patient with cystic fibrosis and abdominal pain. A greater awaremess of the possibility of occult appendiceal abscess may help to avoid this complication."} {"id": "PMID:1263061", "title": "Aganglionosis of the entire bowel.", "content": "Three cases of aganglionosis of the entire bowel are presented. Eight other cases from English literature are reviewed. Two histologic types are noted. The incidence of Hirschsprung's disease in sibling is four out of 11.", "contents": "Aganglionosis of the entire bowel. Three cases of aganglionosis of the entire bowel are presented. Eight other cases from English literature are reviewed. Two histologic types are noted. The incidence of Hirschsprung's disease in sibling is four out of 11."} {"id": "PMID:1263062", "title": "Toxic amoebic colitis and amoebic colon perforation in children: An improved prognosis.", "content": "Fourteen children were treated for complications of severe colonic amebiasis. Seven had colon perforation; seven had toxic amoebic colitis. Those with perforation underwent colon resection limited to the perforation and adjacent abnormal colon. Those having toxic amoebic colitis without perforation were managed by temporary ileostomy. Vigorous general supportive treatment for endotoxic shopck and amebiasis was given pre and postoperatively. Careful barium enema examinations proved safe and effective in diagnosis and follow-up. Ten patients survived (72%), five from each group.", "contents": "Toxic amoebic colitis and amoebic colon perforation in children: An improved prognosis. Fourteen children were treated for complications of severe colonic amebiasis. Seven had colon perforation; seven had toxic amoebic colitis. Those with perforation underwent colon resection limited to the perforation and adjacent abnormal colon. Those having toxic amoebic colitis without perforation were managed by temporary ileostomy. Vigorous general supportive treatment for endotoxic shopck and amebiasis was given pre and postoperatively. Careful barium enema examinations proved safe and effective in diagnosis and follow-up. Ten patients survived (72%), five from each group."} {"id": "PMID:1263063", "title": "Colon interposition for the replacement of the esophagus in children.", "content": "Thirty-two new cases of colon interposition for esophageal reconstruction are presented. Only one late death occurred in this series, which was unrelated to the colon interposition. Fifteen severe complication were observed in five patients with preexisting esophageal atresia and previously complicated courses following disastrous primary esophageal repairs. The most common complication was pneumonia which occurred 13 times. Five late strictures responded well to dilatation or revision. Long-term weight gain was compared between a group of colon transplant patients and a group of patients with repaired esophageal atresia. Although the esophageal atresia group followed the 25th percentile and the colon interposition group followed the 3rd percentile on the growth curve, no significant difference existed in weight gain over 12 yr.", "contents": "Colon interposition for the replacement of the esophagus in children. Thirty-two new cases of colon interposition for esophageal reconstruction are presented. Only one late death occurred in this series, which was unrelated to the colon interposition. Fifteen severe complication were observed in five patients with preexisting esophageal atresia and previously complicated courses following disastrous primary esophageal repairs. The most common complication was pneumonia which occurred 13 times. Five late strictures responded well to dilatation or revision. Long-term weight gain was compared between a group of colon transplant patients and a group of patients with repaired esophageal atresia. Although the esophageal atresia group followed the 25th percentile and the colon interposition group followed the 3rd percentile on the growth curve, no significant difference existed in weight gain over 12 yr."} {"id": "PMID:1263064", "title": "Late repair of bronchial rupture in a child by bronchial replantation.", "content": "A 3-yr-old boy suffered blunt trauma to the anterior chest. Immediate treatment resulted in resolution of acute respiratory distress. Subsequent events led to the recognition of previous bronchial rupture six months later. Primary bronchial repair was not feasible and bronchial replantation onto the trachea was employed. An excellent early result was achieved.", "contents": "Late repair of bronchial rupture in a child by bronchial replantation. A 3-yr-old boy suffered blunt trauma to the anterior chest. Immediate treatment resulted in resolution of acute respiratory distress. Subsequent events led to the recognition of previous bronchial rupture six months later. Primary bronchial repair was not feasible and bronchial replantation onto the trachea was employed. An excellent early result was achieved."} {"id": "PMID:1263077", "title": "Saturable first-pass metabolism of sulfisoxazole N1-acetyl in rats.", "content": "Saturable metabolism of sulfisoxazole N1-acetyl in the rat during the initial pass of the drug from the intestinal lumen through the liver following oral administration of the drug (saturable first-pass metabolism) was investigated. The fraction of the total amount of drug recovered from the urine as the N4-conjugate fraction was apparent following the intravenous administration of sulfisoxazole acetyl or the oral administration of sulfisoxazole at the same dose levels.", "contents": "Saturable first-pass metabolism of sulfisoxazole N1-acetyl in rats. Saturable metabolism of sulfisoxazole N1-acetyl in the rat during the initial pass of the drug from the intestinal lumen through the liver following oral administration of the drug (saturable first-pass metabolism) was investigated. The fraction of the total amount of drug recovered from the urine as the N4-conjugate fraction was apparent following the intravenous administration of sulfisoxazole acetyl or the oral administration of sulfisoxazole at the same dose levels."} {"id": "PMID:1263078", "title": "Mechanism of action of BCG vaccine on neoplastic proliferation and host immune responses.", "content": "BCG (Bacillus Calmette-Guerin) vaccine, Tice strain, caused a threefold increase in spleen weight of normal animals and a fourfold increase in spleen weight of sarcoma-bearing mice. In the latter group, the BCG vaccine caused infiltration of the sarcoma cells into the peritoneum and tumor metastasis in the spleen. Spleen lymphocytes from mice immunized with neuraminidase-treated sarcoma or from mice that had overcome an inoculum (100 cells) and a challenge (10(4) cells) of sarcoma P-1798 were cytotoxic against 51 Cr- or 14C-2-thymidine-labeled sarcoma cells. The serum of these mice enhanced the cytotoxic activity and inhibited the migration of the syngeneic lymphocytes. These serums also inhibited the migration of peritoneal macrophages from guinea pigs immunized with the sarcoma cells. BCG vaccine enhanced the development and growth of sarcoma P-1798; i.e., 50-100 viable sarcoma cells produced solid tumors in 8% of the untreated animals but in 100% of the BCG-treated animals. The serum of BCG-treated sarcoma-bearing animals inhibited the spleen lymphocyte-mediated cytotoxic action. The spleen lymphocytes from the BCG-treated sarcoma-bearing animals had no effect against 51Cr- or 14C-2-thymidine-labelled sarcoma cells. The data indicate that the serum from BCG-treated sarcoma-bearing animals blocks the spleen lymphocyte-mediated cytotoxic activities directed against proliferation and growth of the sarcoma.", "contents": "Mechanism of action of BCG vaccine on neoplastic proliferation and host immune responses. BCG (Bacillus Calmette-Guerin) vaccine, Tice strain, caused a threefold increase in spleen weight of normal animals and a fourfold increase in spleen weight of sarcoma-bearing mice. In the latter group, the BCG vaccine caused infiltration of the sarcoma cells into the peritoneum and tumor metastasis in the spleen. Spleen lymphocytes from mice immunized with neuraminidase-treated sarcoma or from mice that had overcome an inoculum (100 cells) and a challenge (10(4) cells) of sarcoma P-1798 were cytotoxic against 51 Cr- or 14C-2-thymidine-labeled sarcoma cells. The serum of these mice enhanced the cytotoxic activity and inhibited the migration of the syngeneic lymphocytes. These serums also inhibited the migration of peritoneal macrophages from guinea pigs immunized with the sarcoma cells. BCG vaccine enhanced the development and growth of sarcoma P-1798; i.e., 50-100 viable sarcoma cells produced solid tumors in 8% of the untreated animals but in 100% of the BCG-treated animals. The serum of BCG-treated sarcoma-bearing animals inhibited the spleen lymphocyte-mediated cytotoxic action. The spleen lymphocytes from the BCG-treated sarcoma-bearing animals had no effect against 51Cr- or 14C-2-thymidine-labelled sarcoma cells. The data indicate that the serum from BCG-treated sarcoma-bearing animals blocks the spleen lymphocyte-mediated cytotoxic activities directed against proliferation and growth of the sarcoma."} {"id": "PMID:1263079", "title": "Effect of alpha tocopherol (vitamin E) deficiency on intestinal transport of passively absorbed drugs.", "content": "Alpha tocopherol (vitamin E) deficiency has been shown to cause changes in membrane structure. The present study relates alpha tocopherol deficiency with increased rates of transport and absorption of passively absorbed drugs. The pharmacokinetics of barbital in alpha tocopherol-deficient and control rats was studied. The barbital absorption rate constant in deficient animals increased compared to control values. This findings indicates that alpha tocopherol deficiency affects the intestinal membrane structure. This finding was confirmed by studying the intestinal transport of phenolsulfonphthalein, barbital, and salicylate using the everted gut technique. Phenolsulfonphthalein was transported more rapidly through the alpha tocopherol-deficient gut, but this difference was not significant after 30 min, probably due to membrane decomposition. Barbital, which is more lipid soluble and less dependent on changes in pore volume and size, was transported more rapidly through the deficient gut during the entire experiment. The transport rate of salicylate was not altered by the deficiency state. This result was expected since the drug is normally rapidly transported; therefore, comparatively small changes in permeability such as those induced by alpha tocopherol deficiency would be masked. After the oral administration of phenolsulfonphthalein to intact animals, a significantly higher amount of drug was recovered in the urine of the deficient group.", "contents": "Effect of alpha tocopherol (vitamin E) deficiency on intestinal transport of passively absorbed drugs. Alpha tocopherol (vitamin E) deficiency has been shown to cause changes in membrane structure. The present study relates alpha tocopherol deficiency with increased rates of transport and absorption of passively absorbed drugs. The pharmacokinetics of barbital in alpha tocopherol-deficient and control rats was studied. The barbital absorption rate constant in deficient animals increased compared to control values. This findings indicates that alpha tocopherol deficiency affects the intestinal membrane structure. This finding was confirmed by studying the intestinal transport of phenolsulfonphthalein, barbital, and salicylate using the everted gut technique. Phenolsulfonphthalein was transported more rapidly through the alpha tocopherol-deficient gut, but this difference was not significant after 30 min, probably due to membrane decomposition. Barbital, which is more lipid soluble and less dependent on changes in pore volume and size, was transported more rapidly through the deficient gut during the entire experiment. The transport rate of salicylate was not altered by the deficiency state. This result was expected since the drug is normally rapidly transported; therefore, comparatively small changes in permeability such as those induced by alpha tocopherol deficiency would be masked. After the oral administration of phenolsulfonphthalein to intact animals, a significantly higher amount of drug was recovered in the urine of the deficient group."} {"id": "PMID:1263080", "title": "Automated in vitro dissolution rate analysis of potassium in plastic matrix slow release tablets.", "content": "A fully automated system for dissolution rate analysis of potassium in slow release tablets is described. Aliquots are removed after 1, 2, and 4 hr from six samples, and potassium is analyzed in a flame photometer at 768 nm. A complete study of six samples takes 5.5 hr. The system may be run overnight. During the time intervals between the removal of aliquots, the system can be used for the determination of the total assay of tablets.", "contents": "Automated in vitro dissolution rate analysis of potassium in plastic matrix slow release tablets. A fully automated system for dissolution rate analysis of potassium in slow release tablets is described. Aliquots are removed after 1, 2, and 4 hr from six samples, and potassium is analyzed in a flame photometer at 768 nm. A complete study of six samples takes 5.5 hr. The system may be run overnight. During the time intervals between the removal of aliquots, the system can be used for the determination of the total assay of tablets."} {"id": "PMID:1263081", "title": "Structure and toxicity of alkaloids and amino acids of Sophora secundiflora.", "content": "Seeds from Sophora secundiflora were extracted into three major fractions: lipids, alkaloids, and amino acids. Most of the lipid material was composed of steroid esters. These esters were hydrolyzed, and the fatty acid compositions were determined. The major alkaloid component was cytisine, with N-methylcytisine, anagyrine, and the fatty acid compositions were determined. The major alkaloid component was cytisine, with N-methylcytisine, anagyrine, and termopsine in lower concentration. The major free ninhydrin-positive compound was gamma-glutamyltyrosine. In addition to several common amino acids, pipecolic acid and 4-hydroxypipecolic acid were identified. Both the amino acid fraction and the alkaloid fractions caused minor pharmacological disorder when injected into rats. However, when both fractions were simultaneously administered, they were lethal.", "contents": "Structure and toxicity of alkaloids and amino acids of Sophora secundiflora. Seeds from Sophora secundiflora were extracted into three major fractions: lipids, alkaloids, and amino acids. Most of the lipid material was composed of steroid esters. These esters were hydrolyzed, and the fatty acid compositions were determined. The major alkaloid component was cytisine, with N-methylcytisine, anagyrine, and the fatty acid compositions were determined. The major alkaloid component was cytisine, with N-methylcytisine, anagyrine, and termopsine in lower concentration. The major free ninhydrin-positive compound was gamma-glutamyltyrosine. In addition to several common amino acids, pipecolic acid and 4-hydroxypipecolic acid were identified. Both the amino acid fraction and the alkaloid fractions caused minor pharmacological disorder when injected into rats. However, when both fractions were simultaneously administered, they were lethal."} {"id": "PMID:1263082", "title": "Dissolution rates of high energy sulfathiazole--povidone coprecipitates II: characterization of form of drug controlling its dissolution rate via solubility studies.", "content": "Solubility studies were made to characterize the form of sulfathiazole controlling the rate of dissolution exhibited in previously reported dissolution rate studies of sulfathiazole coprecipitated with povidone. The aqueous solubility of the high energy form of sulfathiazole obtained using sulfathiazole--povidone coprecipitates was determined in the presence of polymer in solution. Its aqueous solubility in the absence of polymer was determined by extrapolation. The solubility value was much greater than either the supercooled melt or the crystalline forms of sulfathiazole. Stabilization of these sulfathiazole solutions supersaturated with respect to the more stable crystalline form was achieved by the addition of sufficient polymer to the solution to prevent nucleation of the crystalline form. The concentration of polymer required to prevent nucleation of the crystalline forms was much higher than the previously reported concentrations required to inhibit crystal growth of sulfathiazole. The ratio of the solubility value obtained for the coprecipitated sulfathiazole as compared with its crystalline form I was in agreement with the ratio of their dissolution rates obtained the plateau regions of the dissolution rate experiments reported previously. The extrapolated aqueous solubility values in the absence of povidone were obtained as a function of temperature and were utilized to obtain thermodynamic parameters. The difference in the heat of solution of the two forms of sulfathiazole from the slope of the van't Hoff plots of the extrapolated solubility values was 1618 cal/mole, in excellent agreement with the literature value. The free energy, enthalpy, and entropy at 27 degrees for the coprecipitated drug relative to its crystalline form I were 1125 cal/mole, 8439 cal/mole, and 24 eu, respectively, indicating the high degree of molecular randomness and lack of structure in these high energy systems. These results provide strong evidence for the presence of an amorphous state of sulfathiazole as the controlling phase of both the solubility and dissolution rate experiments involving the high energy form of sulfathiazole obtained by coprecipitation with povidone.", "contents": "Dissolution rates of high energy sulfathiazole--povidone coprecipitates II: characterization of form of drug controlling its dissolution rate via solubility studies. Solubility studies were made to characterize the form of sulfathiazole controlling the rate of dissolution exhibited in previously reported dissolution rate studies of sulfathiazole coprecipitated with povidone. The aqueous solubility of the high energy form of sulfathiazole obtained using sulfathiazole--povidone coprecipitates was determined in the presence of polymer in solution. Its aqueous solubility in the absence of polymer was determined by extrapolation. The solubility value was much greater than either the supercooled melt or the crystalline forms of sulfathiazole. Stabilization of these sulfathiazole solutions supersaturated with respect to the more stable crystalline form was achieved by the addition of sufficient polymer to the solution to prevent nucleation of the crystalline form. The concentration of polymer required to prevent nucleation of the crystalline forms was much higher than the previously reported concentrations required to inhibit crystal growth of sulfathiazole. The ratio of the solubility value obtained for the coprecipitated sulfathiazole as compared with its crystalline form I was in agreement with the ratio of their dissolution rates obtained the plateau regions of the dissolution rate experiments reported previously. The extrapolated aqueous solubility values in the absence of povidone were obtained as a function of temperature and were utilized to obtain thermodynamic parameters. The difference in the heat of solution of the two forms of sulfathiazole from the slope of the van't Hoff plots of the extrapolated solubility values was 1618 cal/mole, in excellent agreement with the literature value. The free energy, enthalpy, and entropy at 27 degrees for the coprecipitated drug relative to its crystalline form I were 1125 cal/mole, 8439 cal/mole, and 24 eu, respectively, indicating the high degree of molecular randomness and lack of structure in these high energy systems. These results provide strong evidence for the presence of an amorphous state of sulfathiazole as the controlling phase of both the solubility and dissolution rate experiments involving the high energy form of sulfathiazole obtained by coprecipitation with povidone."} {"id": "PMID:1263083", "title": "Catharanthus alkaloids XXXII: isolation of alkaloids from Catharanthus trichophyllus roots and structure elucidation of cathaphylline.", "content": "Further examination of the cytotoxic alkaloid fractions of Catharanthus trichophyllus roots afforded nine alkaloids. Two of these alkaloids, lochnericine and horhammericine, are responsible for part of the cytotoxic activity. The structure elucidation of cathaphylline, a new beta-anilino acrylate derivative, is described.", "contents": "Catharanthus alkaloids XXXII: isolation of alkaloids from Catharanthus trichophyllus roots and structure elucidation of cathaphylline. Further examination of the cytotoxic alkaloid fractions of Catharanthus trichophyllus roots afforded nine alkaloids. Two of these alkaloids, lochnericine and horhammericine, are responsible for part of the cytotoxic activity. The structure elucidation of cathaphylline, a new beta-anilino acrylate derivative, is described."} {"id": "PMID:1263084", "title": "GLC determination of griseofulvin in human plasma.", "content": "A specific and quantitative GLC method for the determination of griseofulvin in human plasma is described. The method involves extraction with ether, evaporation, addition of the internal standard dissolved in benzene, and GLC analysis using an electron-capture detector. The sensitivity of the method is 0.05 mug/ml of plasma. The results obtained with this specific GLC method were compared with the results obtained with the more frequently used spectroflurometric method by analyzing duplicate plasma samples obtained from 12 subjects following a single dose of griseofulvin. It was deduced that the 30% higher plasma levels obtained spectrofluormetrically were due to the coextraction and presence of the metabolite 6-demethylgriseofulvin in the assay solutions.", "contents": "GLC determination of griseofulvin in human plasma. A specific and quantitative GLC method for the determination of griseofulvin in human plasma is described. The method involves extraction with ether, evaporation, addition of the internal standard dissolved in benzene, and GLC analysis using an electron-capture detector. The sensitivity of the method is 0.05 mug/ml of plasma. The results obtained with this specific GLC method were compared with the results obtained with the more frequently used spectroflurometric method by analyzing duplicate plasma samples obtained from 12 subjects following a single dose of griseofulvin. It was deduced that the 30% higher plasma levels obtained spectrofluormetrically were due to the coextraction and presence of the metabolite 6-demethylgriseofulvin in the assay solutions."} {"id": "PMID:1263085", "title": "Granule consolidation during compaction.", "content": "The deformation of small cylindrical aggregates of dibasic calcium phosphate was measured during compaction. An analogy between these aggregates and cylindrical granules was proposed. No change in the original shape of the aggregates occurred; the cylindrical shape was maintained even at high compaction pressures. Relaxation of the aggregates occurred at pressures higher than 420 MNm-2 (60.9 x 10(3) lb in.-2) when removed from the compacts, but no relaxation took place at pressures below this value. In addition, the aggregates relaxed by an increase in thickness only; there was no corresponding change in diameter. Up to a pressure of 200 MNm-2 (29.0 x 10(3) lb in.-2), an increase in aggregate diameter occurred, which was accompanied by a reduction in thickness. This change produced only a small reduction in volume, which was attributable to interparticulate slippage resulting in a closer packed arrangement. At a pressure of 200 MNm-2, the aggregate diameter no longer increased because solid bridges were formed between the particles and the die wall, preventing further spreading. From 200 to 420 MNm-2, failure of the material occurred by plastic deformation, which produced only a decrease in aggregate thickness. From 420 to 800 MNm-2 (116.0 x 10(3) lb in.-2), a structure was formed that could support the applied load without further reduction of thickness, and this structure was shown to behave elastically.", "contents": "Granule consolidation during compaction. The deformation of small cylindrical aggregates of dibasic calcium phosphate was measured during compaction. An analogy between these aggregates and cylindrical granules was proposed. No change in the original shape of the aggregates occurred; the cylindrical shape was maintained even at high compaction pressures. Relaxation of the aggregates occurred at pressures higher than 420 MNm-2 (60.9 x 10(3) lb in.-2) when removed from the compacts, but no relaxation took place at pressures below this value. In addition, the aggregates relaxed by an increase in thickness only; there was no corresponding change in diameter. Up to a pressure of 200 MNm-2 (29.0 x 10(3) lb in.-2), an increase in aggregate diameter occurred, which was accompanied by a reduction in thickness. This change produced only a small reduction in volume, which was attributable to interparticulate slippage resulting in a closer packed arrangement. At a pressure of 200 MNm-2, the aggregate diameter no longer increased because solid bridges were formed between the particles and the die wall, preventing further spreading. From 200 to 420 MNm-2, failure of the material occurred by plastic deformation, which produced only a decrease in aggregate thickness. From 420 to 800 MNm-2 (116.0 x 10(3) lb in.-2), a structure was formed that could support the applied load without further reduction of thickness, and this structure was shown to behave elastically."} {"id": "PMID:1263086", "title": "Effect of cycloamyloses on apparent dissociation constants of carboxylic acids and phenols: equilibrium analytical selectivity induced by complex formation.", "content": "Apparent dissociation constants of organic acids were determined by potentiometric titration in the presence of cyclohexaamylose or cycloheptaamylose. The quantity deltapKa' = pKa' (cycloamylose)-pKa (water) was positive or zero for all carboxylic acids studied and negative or zero for all phenols. The term delta pKa' can be related to the cycloamylose concentration, K11alpha, and K11b, where K11a and K11b are 1:1 stability constants for complexes of the acid and the anion, respectively. From the dependen1a and K11b can be obtained. If deltapKa' not equal to 0, then K11a not equal to K11b; for carboxylic acids, K11a greater than or equal to K11b; for phenols, K11b greater than or equal to K11a. Because of variable pKa' shifts, it is possible to carry out differentiating titrations of some acid mixtures in cycloamylose solutions, whereas the same acids cannot be differentiated in water. If an acid is weakened by cycloamylose, its conjugate base is strengthened, and some carboxylate salts can be readily titrated in the presence of a cycloamylose.", "contents": "Effect of cycloamyloses on apparent dissociation constants of carboxylic acids and phenols: equilibrium analytical selectivity induced by complex formation. Apparent dissociation constants of organic acids were determined by potentiometric titration in the presence of cyclohexaamylose or cycloheptaamylose. The quantity deltapKa' = pKa' (cycloamylose)-pKa (water) was positive or zero for all carboxylic acids studied and negative or zero for all phenols. The term delta pKa' can be related to the cycloamylose concentration, K11alpha, and K11b, where K11a and K11b are 1:1 stability constants for complexes of the acid and the anion, respectively. From the dependen1a and K11b can be obtained. If deltapKa' not equal to 0, then K11a not equal to K11b; for carboxylic acids, K11a greater than or equal to K11b; for phenols, K11b greater than or equal to K11a. Because of variable pKa' shifts, it is possible to carry out differentiating titrations of some acid mixtures in cycloamylose solutions, whereas the same acids cannot be differentiated in water. If an acid is weakened by cycloamylose, its conjugate base is strengthened, and some carboxylate salts can be readily titrated in the presence of a cycloamylose."} {"id": "PMID:1263087", "title": "GLC determination of plasma concentrations of phenprocoumon.", "content": "A GLC method for the quantitative estimation of phenprocoumon from plasma is described. Plasma containing phenprocoumon, to which a known amount of phenytoin is added as the internal standard, is acidified and extracted with ethylene dichloride. The drug and the internal standard are then back-extracted into alkali, which is acidified and reextracted with ethylene dichloride. The organic extract is evaporated, and the evaporated residue is mixed with 50 mul of trimethylanilinium hydroxide in methanol. Aliquots (1-2 mul) are injected into a gas chromatography equipped with a flame-ionization detector in which the injection port is held at 325 degrees. The methyl derivatives of phenprocoumon and the internal standard give sharp, well-separated, symmetrical peaks. The method is of sufficient sensitivity to determine 0.125 mug/ml of the drug in plasma with a coefficient of variation of 7%.", "contents": "GLC determination of plasma concentrations of phenprocoumon. A GLC method for the quantitative estimation of phenprocoumon from plasma is described. Plasma containing phenprocoumon, to which a known amount of phenytoin is added as the internal standard, is acidified and extracted with ethylene dichloride. The drug and the internal standard are then back-extracted into alkali, which is acidified and reextracted with ethylene dichloride. The organic extract is evaporated, and the evaporated residue is mixed with 50 mul of trimethylanilinium hydroxide in methanol. Aliquots (1-2 mul) are injected into a gas chromatography equipped with a flame-ionization detector in which the injection port is held at 325 degrees. The methyl derivatives of phenprocoumon and the internal standard give sharp, well-separated, symmetrical peaks. The method is of sufficient sensitivity to determine 0.125 mug/ml of the drug in plasma with a coefficient of variation of 7%."} {"id": "PMID:1263088", "title": "Analysis of tetracycline in pharmaceutical preparations by improved high-performance liquid chromatographic method.", "content": "The analysis of tetracycline in pharmaceutical preparations by an improved high-performance liquid chromatographic (HPLC) method is described. The improved method uses a 30-cm long stainless steel column packed with octadecylsilane bonded on 10-mum silica gel, with a linear gradient from 10 to 60% acetonitrile in pH 2.5, 0.02 M phosphate buffer in 11 min at a flow rate of 1.0 ml/min (68 atm). The resolution functions obtained between 4-epitetracycline and tetracycline and between 4-epianhydrotetracycline and anhydrotetracycline were improved 150 and 250%, respectively. The analysis of a tetracycline sample takes approximately 16 min; the original method required more tan 25 min. The relative standard deviation for the analysis of tetracycline powder was 0.66%, and the recovery of 4-epianhydrotetracycline added in tetracycline was linear over the 0.3-100% range. Recovery of tetracycline from products was better than 99.6% at label concentration. The drug content of products as calculated from the HPLC data agreed well with those of the microbiological assay methods.", "contents": "Analysis of tetracycline in pharmaceutical preparations by improved high-performance liquid chromatographic method. The analysis of tetracycline in pharmaceutical preparations by an improved high-performance liquid chromatographic (HPLC) method is described. The improved method uses a 30-cm long stainless steel column packed with octadecylsilane bonded on 10-mum silica gel, with a linear gradient from 10 to 60% acetonitrile in pH 2.5, 0.02 M phosphate buffer in 11 min at a flow rate of 1.0 ml/min (68 atm). The resolution functions obtained between 4-epitetracycline and tetracycline and between 4-epianhydrotetracycline and anhydrotetracycline were improved 150 and 250%, respectively. The analysis of a tetracycline sample takes approximately 16 min; the original method required more tan 25 min. The relative standard deviation for the analysis of tetracycline powder was 0.66%, and the recovery of 4-epianhydrotetracycline added in tetracycline was linear over the 0.3-100% range. Recovery of tetracycline from products was better than 99.6% at label concentration. The drug content of products as calculated from the HPLC data agreed well with those of the microbiological assay methods."} {"id": "PMID:1263089", "title": "Synthesis of substituted thiobenzoxazoles/benzothiazoles: inhibition of cellular respiratory and monoamine oxidase activities and anticonvulsant property.", "content": "Several 2-(substituted alkoxy/hydrazinocarbonyl acetanilidothio)benzoxazoles/benzothiazoles were synthesized and characterized by their sharp melting points, elemental analyses, and IR spectra. All thiobenzoxazoles/benzothiazoles possessed low anticonvulsant activity, which was reflected by the 10-40% protection afforded by these compounds against pentylenetetrazol-induced convulsions. All thiobenzoxazoles/benzothiazoles inhibited selectively the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, DL-isocitrate, and alpha-ketoglutarate by rat brain homogenates. NAD-independent oxidation of succinate remained unaltered. All 2-(substituted hydrazinocarbonyl acetanilidothio)benzoxazoles/benzothiazoles inhibited monoamine oxidase activity of rat brain homogenates. Greater monoamine oxidase inhibition was observed with thiobenzothiazoles than with the corresponding thiobenzoxazoles/benzothiazoles was found to be unrelated with their ability to inhibit cellular respiratory and monoamine oxidase activities of rat brain homogenates.", "contents": "Synthesis of substituted thiobenzoxazoles/benzothiazoles: inhibition of cellular respiratory and monoamine oxidase activities and anticonvulsant property. Several 2-(substituted alkoxy/hydrazinocarbonyl acetanilidothio)benzoxazoles/benzothiazoles were synthesized and characterized by their sharp melting points, elemental analyses, and IR spectra. All thiobenzoxazoles/benzothiazoles possessed low anticonvulsant activity, which was reflected by the 10-40% protection afforded by these compounds against pentylenetetrazol-induced convulsions. All thiobenzoxazoles/benzothiazoles inhibited selectively the nicotinamide adenine dinucleotide (NAD)-dependent oxidation of pyruvate, DL-isocitrate, and alpha-ketoglutarate by rat brain homogenates. NAD-independent oxidation of succinate remained unaltered. All 2-(substituted hydrazinocarbonyl acetanilidothio)benzoxazoles/benzothiazoles inhibited monoamine oxidase activity of rat brain homogenates. Greater monoamine oxidase inhibition was observed with thiobenzothiazoles than with the corresponding thiobenzoxazoles/benzothiazoles was found to be unrelated with their ability to inhibit cellular respiratory and monoamine oxidase activities of rat brain homogenates."} {"id": "PMID:1263090", "title": "Synthesis of N,N'-bis(3-substituted benzylideneaminopropyl)-piperazines and their anti-inflammatory, antiproteolytic, and anticonvulsant properties.", "content": "Some N,N'-bis(3-substituted benzylideneaminopropyl) piperazines were synthesized and characterized by their sharp melting points and elemental analyses. These substituted piperazines possessed anti-inflammatory activity, and the protection afforded by these compounds against carrageenan-induced edema ranged from 23 to 67%. The antiproteolytic activity of these piperazines was reflected by their ability to inhibit in vitro hydrolysis of bovine serum albumin and casein by trypsin. The inhibition of trypsin-induced hydrolysis was concentration dependent and competitive in nature.", "contents": "Synthesis of N,N'-bis(3-substituted benzylideneaminopropyl)-piperazines and their anti-inflammatory, antiproteolytic, and anticonvulsant properties. Some N,N'-bis(3-substituted benzylideneaminopropyl) piperazines were synthesized and characterized by their sharp melting points and elemental analyses. These substituted piperazines possessed anti-inflammatory activity, and the protection afforded by these compounds against carrageenan-induced edema ranged from 23 to 67%. The antiproteolytic activity of these piperazines was reflected by their ability to inhibit in vitro hydrolysis of bovine serum albumin and casein by trypsin. The inhibition of trypsin-induced hydrolysis was concentration dependent and competitive in nature."} {"id": "PMID:1263091", "title": "NMR study of amphetamines using europium shift reagents.", "content": "Amphetamine and certain of its methoxylated derivatives show a high degree of interaction with NMR shift reagents of the type tris (1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione)europium(III). The shifts are not accompanied by appreciable line broadening, and both the aliphatic and aromatic protons can be resolved. The strong interaction between amine and shift reagent diminishes rapidly as the amine function is alkylated. For derivatives containing ortho-methoxyl groups, a weaker interaction with this functionality also becomes evident as the amine is alkylated. The stereospecificity of the shifting process was investigated by employing tris[3-(trifluoroacetyl)-d-camphorato]europium(III), a chiral shift reagent, with stereochemically pure enantiomers and known enantiomeric mixtures. Although certain (R)-enantiomers showed greater downfield C-methyl groups shifts, these shift differences from the corresponding (S)-enantiomers were small and not well resolved.", "contents": "NMR study of amphetamines using europium shift reagents. Amphetamine and certain of its methoxylated derivatives show a high degree of interaction with NMR shift reagents of the type tris (1,1,1,2,2,3,3-heptafluoro-7,7-dimethyl-4,6-octanedione)europium(III). The shifts are not accompanied by appreciable line broadening, and both the aliphatic and aromatic protons can be resolved. The strong interaction between amine and shift reagent diminishes rapidly as the amine function is alkylated. For derivatives containing ortho-methoxyl groups, a weaker interaction with this functionality also becomes evident as the amine is alkylated. The stereospecificity of the shifting process was investigated by employing tris[3-(trifluoroacetyl)-d-camphorato]europium(III), a chiral shift reagent, with stereochemically pure enantiomers and known enantiomeric mixtures. Although certain (R)-enantiomers showed greater downfield C-methyl groups shifts, these shift differences from the corresponding (S)-enantiomers were small and not well resolved."} {"id": "PMID:1263092", "title": "Intestinal secretion of erythromycin base.", "content": "Erythromycin fluxes into rabbit midjejunal segments were studied. When erythromycin was infused into the jugular vein of anesthetized rabbits, the antibiotic was secreted into the segments at a rate of 0.0136 +/- 0.0023 mg/min. Preloading of the segments with five and 20 times the plasma concentration did not diminish this secretion. Protein binding of the antibiotic within the lumen could not explain this secretion, since both ultrafiltration and chromatography of luminal solutions indicated that the biological activity was free erythromycin. Moreover, the transmural potential across the intestinal mucosa is likely to be theprincipal driving force, since greater than 80 mv would be required to sustain the observed secretion against an imposed 20-fold concentration difference between blood and lumen. The best explanation for the intestinal secretion of erythromycin appears to be an active transport pathway capable of concentrating erythromycin in the lumen. It is not clear what endogenous substances are transported by this pathway.", "contents": "Intestinal secretion of erythromycin base. Erythromycin fluxes into rabbit midjejunal segments were studied. When erythromycin was infused into the jugular vein of anesthetized rabbits, the antibiotic was secreted into the segments at a rate of 0.0136 +/- 0.0023 mg/min. Preloading of the segments with five and 20 times the plasma concentration did not diminish this secretion. Protein binding of the antibiotic within the lumen could not explain this secretion, since both ultrafiltration and chromatography of luminal solutions indicated that the biological activity was free erythromycin. Moreover, the transmural potential across the intestinal mucosa is likely to be theprincipal driving force, since greater than 80 mv would be required to sustain the observed secretion against an imposed 20-fold concentration difference between blood and lumen. The best explanation for the intestinal secretion of erythromycin appears to be an active transport pathway capable of concentrating erythromycin in the lumen. It is not clear what endogenous substances are transported by this pathway."} {"id": "PMID:1263093", "title": "Filtration rates of pharmaceutical suspension systems.", "content": "This study was undertaken to find it a correlation exists between the filtration rate and the Hu/Ho ratio. For this purpose, flocculated and coagulated structures of sulfamerazine were used. Suspension settling profiles and filtration rates, using additives and additive-free sulfamerazine suspensions, were studied. A straight-line correlation was found. Effects of filter bed parameters on refiltration rates were studied, and a relationship was found by the use of the Kozeny-Carman equation. A straight-line relationship existed between the H1/Ho ratio and the filtration rate exhibited by the different suspension aggregates.", "contents": "Filtration rates of pharmaceutical suspension systems. This study was undertaken to find it a correlation exists between the filtration rate and the Hu/Ho ratio. For this purpose, flocculated and coagulated structures of sulfamerazine were used. Suspension settling profiles and filtration rates, using additives and additive-free sulfamerazine suspensions, were studied. A straight-line correlation was found. Effects of filter bed parameters on refiltration rates were studied, and a relationship was found by the use of the Kozeny-Carman equation. A straight-line relationship existed between the H1/Ho ratio and the filtration rate exhibited by the different suspension aggregates."} {"id": "PMID:1263094", "title": "Nonaqueous titration of sulfates of quinine and quinidine using barium acetate.", "content": "A nonaqueous titrimetric method is proposed for determining the diastereomeric sulfates of quinine and quinidine. The sulfuric acid content of the alkaloid salts is precipitated, in the form of barium sulfate, with acetous barium acetate solution before the liberated alkaloid is titrated; the necessary calculations are provided. A favorable characteristic of the proposed procedure is the accuracy, speed, and ease of performance. The mean percent recoveries (p = 0.05) obtained with the proposed method for the sulfates of quinine and quinidine were 98.84 +/- 1.00 and 99.74 +/- 1.27, respectively, compared with 100.73 +/- 1.44 and 100.82 +/- 1.16, respectively, when the BP 1968 procedure was applied.", "contents": "Nonaqueous titration of sulfates of quinine and quinidine using barium acetate. A nonaqueous titrimetric method is proposed for determining the diastereomeric sulfates of quinine and quinidine. The sulfuric acid content of the alkaloid salts is precipitated, in the form of barium sulfate, with acetous barium acetate solution before the liberated alkaloid is titrated; the necessary calculations are provided. A favorable characteristic of the proposed procedure is the accuracy, speed, and ease of performance. The mean percent recoveries (p = 0.05) obtained with the proposed method for the sulfates of quinine and quinidine were 98.84 +/- 1.00 and 99.74 +/- 1.27, respectively, compared with 100.73 +/- 1.44 and 100.82 +/- 1.16, respectively, when the BP 1968 procedure was applied."} {"id": "PMID:1263095", "title": "Quantitative GLC determination of codeine in plasma.", "content": "A sensitive and accurate GLC method for quantitating codeine in plasma at levels of 50 ng/ml, with limits of detection as low as 5 ng/ml, is described.", "contents": "Quantitative GLC determination of codeine in plasma. A sensitive and accurate GLC method for quantitating codeine in plasma at levels of 50 ng/ml, with limits of detection as low as 5 ng/ml, is described."} {"id": "PMID:1263096", "title": "Aqueous solubility of 14C-triamcinolone acetonide.", "content": "The blue tetrazolium colorimetric assay has often been employed in the analysis of corticosteroids. However, the reaction between blue tetrazolium and corticosteroids partly depends on the apparent pH of the system. In an earlier study of the temperature dependence of the solubility and dissolution of triamcinolone acetonide in aqueous dissolution media (distilled water and 0.2-1.0 M potassium chloride solutions), pH was not considered. To determine the reliability of the data previously reported, the solubility of 14C-triamcinolone acetonide was determined by a radioisotopic method. The results of the analyses, using a liquid scintillation counting system, indicate that the steroid solubility is generally about 20% lower than that reported previously.", "contents": "Aqueous solubility of 14C-triamcinolone acetonide. The blue tetrazolium colorimetric assay has often been employed in the analysis of corticosteroids. However, the reaction between blue tetrazolium and corticosteroids partly depends on the apparent pH of the system. In an earlier study of the temperature dependence of the solubility and dissolution of triamcinolone acetonide in aqueous dissolution media (distilled water and 0.2-1.0 M potassium chloride solutions), pH was not considered. To determine the reliability of the data previously reported, the solubility of 14C-triamcinolone acetonide was determined by a radioisotopic method. The results of the analyses, using a liquid scintillation counting system, indicate that the steroid solubility is generally about 20% lower than that reported previously."} {"id": "PMID:1263097", "title": "Fluorometric assay of verapamil in biological fluids and tissues.", "content": "Verapamil concentrations in blood, urinee, or tissue homogenates may be measured fluorometrically in the 0.1-10-mug/ml range after extraction into heptane and back-extraction into acid; recovery rates are above 87%. The drug apparently is eliminated rapidly in guinea pigs, with a plasma half-life of 45 min.", "contents": "Fluorometric assay of verapamil in biological fluids and tissues. Verapamil concentrations in blood, urinee, or tissue homogenates may be measured fluorometrically in the 0.1-10-mug/ml range after extraction into heptane and back-extraction into acid; recovery rates are above 87%. The drug apparently is eliminated rapidly in guinea pigs, with a plasma half-life of 45 min."} {"id": "PMID:1263098", "title": "Homogeneity of Pasteurella avicida bacterin.", "content": "A simple rapid procedure is described for determining whether an emulsified bacterin is homogenous by measuring the UV absorbances of chloroform-washed centrifugates. These absorbances appear to depend on nucleic acid content.", "contents": "Homogeneity of Pasteurella avicida bacterin. A simple rapid procedure is described for determining whether an emulsified bacterin is homogenous by measuring the UV absorbances of chloroform-washed centrifugates. These absorbances appear to depend on nucleic acid content."} {"id": "PMID:1263099", "title": "Binding of sulfisoxazole to protein fractions of tears.", "content": "By using equilibrium dialysis experiments, it is shown that sulfisoxazole binds extensively with albumin and alpha-globulin and to a lesser extent with gamma-globulin and lysozyme, all of which are normal components of tears. The binding of sulfisoxazole to the various protein fractions quantitatively accounts for the over-all binding of this drug to human tears. It is suggested that to predict the binding of drugs to proteins in lacrimal fluid, both in normal and pathological conditions, it is necessary to conduct binding studies of the drug with the major protein fractions of tears. More-over, it is essential to know the composition of the major protein fractions of tears in both normal and various pathological conditions to conduct the necessary in vitro binding studies.", "contents": "Binding of sulfisoxazole to protein fractions of tears. By using equilibrium dialysis experiments, it is shown that sulfisoxazole binds extensively with albumin and alpha-globulin and to a lesser extent with gamma-globulin and lysozyme, all of which are normal components of tears. The binding of sulfisoxazole to the various protein fractions quantitatively accounts for the over-all binding of this drug to human tears. It is suggested that to predict the binding of drugs to proteins in lacrimal fluid, both in normal and pathological conditions, it is necessary to conduct binding studies of the drug with the major protein fractions of tears. More-over, it is essential to know the composition of the major protein fractions of tears in both normal and various pathological conditions to conduct the necessary in vitro binding studies."} {"id": "PMID:1263100", "title": "Phosphorus-nitrogen compounds XIX: distribution of 32P and effect of an active oncolytic on intracerebral leukemia in rodents.", "content": "P,P-Bis(1-aziridinyl)-N-1-adamantylphosphinic amide displayed oncolytic activity against intracerebral and intraperitoneal L-1210 leukemia. Administration of the isotope-labeled compound to rats shows 32P distribution to the brain.", "contents": "Phosphorus-nitrogen compounds XIX: distribution of 32P and effect of an active oncolytic on intracerebral leukemia in rodents. P,P-Bis(1-aziridinyl)-N-1-adamantylphosphinic amide displayed oncolytic activity against intracerebral and intraperitoneal L-1210 leukemia. Administration of the isotope-labeled compound to rats shows 32P distribution to the brain."} {"id": "PMID:1263101", "title": "Influence of aspirin formulation and dose on concentration of total salicylate in rat kidney.", "content": "Rats received the equivalent of 100, 250, 500, or 700 mg/kg of 14C-aspirin orally as a suspension or as a solution of a buffered, effervescent, aspirin-containing product. Animals in each dose group were sacrificed at time intervals ranging from 0.5 to 24 hr after dosing. The 14C content of whole blood, plasma, and homogenized whole kidney (after perfusion) was determined. The concentration of total salicylate proved to be dose dependent and was lower in tissues from rats receiving the buffered, effervescent product, especially at the higher doses. The results suggest that salicylate-induced renal toxicity should be less likely to occur after administration of the buffered, effervescent formulation.", "contents": "Influence of aspirin formulation and dose on concentration of total salicylate in rat kidney. Rats received the equivalent of 100, 250, 500, or 700 mg/kg of 14C-aspirin orally as a suspension or as a solution of a buffered, effervescent, aspirin-containing product. Animals in each dose group were sacrificed at time intervals ranging from 0.5 to 24 hr after dosing. The 14C content of whole blood, plasma, and homogenized whole kidney (after perfusion) was determined. The concentration of total salicylate proved to be dose dependent and was lower in tissues from rats receiving the buffered, effervescent product, especially at the higher doses. The results suggest that salicylate-induced renal toxicity should be less likely to occur after administration of the buffered, effervescent formulation."} {"id": "PMID:1263102", "title": "Measurement of sulfamethizole clearance rate by nonthrombogenic constant blood-withdrawal system.", "content": "A method for the measurement of the total body clearance rate (CR) of drugs is described. It involves a single intravenous injection of a known quantity of the drug (D) and automatic integration of the plasma concentration curve, using a portable, nonthrombogenic, constant blood-withdrawal system. When blood withdrawal is carried out until the concentration of the drug in the plasma approaches zero, the concentration of the drug in the collected pool, the integrated concentration (ICT) multiplied by the time of collection (T) yields the integral of the concentration curve: (see article). The method was tested by measuring the clearance rate of sulfamethizole in five dogs by the established constant infusion method. At three plasma levels (25, 75, and 200 mg/liter), the plasma concentration had no significant effect on the clearance rate. The clearance rate of sulfamethizole was subsequently measured in the same dogs by the new single-injection constant withdrawal method. Multiple blood samples were collected at 15-min intervals simultaneously with the constant withdrawal of blood. There was no significant difference between the clearance rate of sulfamethizole measured by the two methods. The initial peak mean concentration of the drug from the time of injection (t = 0) to the time of the first blood sampling (t = 15 min) was calculated from the difference between (see article) obtained by the constant withdrawal method and that obtained from the results of the multiple blood withdrawals by the trapezoidal rule. The integrated concentration IC15 was significantly higher than its estimation by the semilogarithmic linear regression method.", "contents": "Measurement of sulfamethizole clearance rate by nonthrombogenic constant blood-withdrawal system. A method for the measurement of the total body clearance rate (CR) of drugs is described. It involves a single intravenous injection of a known quantity of the drug (D) and automatic integration of the plasma concentration curve, using a portable, nonthrombogenic, constant blood-withdrawal system. When blood withdrawal is carried out until the concentration of the drug in the plasma approaches zero, the concentration of the drug in the collected pool, the integrated concentration (ICT) multiplied by the time of collection (T) yields the integral of the concentration curve: (see article). The method was tested by measuring the clearance rate of sulfamethizole in five dogs by the established constant infusion method. At three plasma levels (25, 75, and 200 mg/liter), the plasma concentration had no significant effect on the clearance rate. The clearance rate of sulfamethizole was subsequently measured in the same dogs by the new single-injection constant withdrawal method. Multiple blood samples were collected at 15-min intervals simultaneously with the constant withdrawal of blood. There was no significant difference between the clearance rate of sulfamethizole measured by the two methods. The initial peak mean concentration of the drug from the time of injection (t = 0) to the time of the first blood sampling (t = 15 min) was calculated from the difference between (see article) obtained by the constant withdrawal method and that obtained from the results of the multiple blood withdrawals by the trapezoidal rule. The integrated concentration IC15 was significantly higher than its estimation by the semilogarithmic linear regression method."} {"id": "PMID:1263103", "title": "Volume of distribution as a function of time.", "content": "A single definition for all volume terms in pharmacokinetic modeling is proposed; this parameter is considered as a function of time. This definition will represent the kinetic nature of pharmacokinetic models and will provide a highly sensitive parameter for correlation with pharmacological responses.", "contents": "Volume of distribution as a function of time. A single definition for all volume terms in pharmacokinetic modeling is proposed; this parameter is considered as a function of time. This definition will represent the kinetic nature of pharmacokinetic models and will provide a highly sensitive parameter for correlation with pharmacological responses."} {"id": "PMID:1263104", "title": "Bioavailability of flufenamic acid in hard and soft gelatin capsules.", "content": "The biological availability of flufenamic acid after oral administration of the drug in both hard and soft gelatin capsules was studied in dogs and humans. The soft gelatin capsules produced consistently higher plasma concentration-time curves.", "contents": "Bioavailability of flufenamic acid in hard and soft gelatin capsules. The biological availability of flufenamic acid after oral administration of the drug in both hard and soft gelatin capsules was studied in dogs and humans. The soft gelatin capsules produced consistently higher plasma concentration-time curves."} {"id": "PMID:1263105", "title": "GLC determination of degradation of two related amine uptake inhibitors.", "content": "A convenient GLC method was developed to assay the chemically related CNS agents dl-3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine (Ia) and dl-3-(0-methoxy-phenoxy)-N-methyl-3-phenylpropylamine (Ib). Subsequently, this GLC method was used to monitor the stability of Ia and Ib in acidic and basic media. These CNS agents were stable in basic solution but labile under acid conditions, and the degradations of both compounds approximated pseudo-first-order kinetics. Products formed during the acid hydrolysis of Ia and Ib were identified and were shown not to interfere in the GLC assays of the parent ethers.", "contents": "GLC determination of degradation of two related amine uptake inhibitors. A convenient GLC method was developed to assay the chemically related CNS agents dl-3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine (Ia) and dl-3-(0-methoxy-phenoxy)-N-methyl-3-phenylpropylamine (Ib). Subsequently, this GLC method was used to monitor the stability of Ia and Ib in acidic and basic media. These CNS agents were stable in basic solution but labile under acid conditions, and the degradations of both compounds approximated pseudo-first-order kinetics. Products formed during the acid hydrolysis of Ia and Ib were identified and were shown not to interfere in the GLC assays of the parent ethers."} {"id": "PMID:1263110", "title": "Effects of halothane anesthesia on the biodisposition of ketamine in rats.", "content": "Ketamine, a highly lipophilic drug, was rapidly distributed into highly vascular organs and subsequently redistributed to less well perfused tissues, with concurrent hepatic metabolism and urinary and biliary excretion, after both i. m. and i. v. administration in the rat. Halothane, a potent cardiovascular depressant, was found to prolong the plasma and brain half-life of ketamine (50 mg/kg i.m.) and also increased the duration of ketamine-induced ataxia when the two drugs were administered concomitantly. Halothane anesthesia (0.8% halothane in oxygen) produced a decrease in the rate of uptake and delayed distribution and redistribution of ketamine (50 mg/kg i. m.), while the rate of urinary excretion of ketamine was not significantly altered. Similarly, redistribution of intravenously administered ketamine (30 mg/kg i. v.) was slowed in the presence of halothane. In vitro hepatic microsomal metabolism of ketamine and its principle N-demethylated metabolite, metabolite I, was inhibited noncompetitively by halothane with inhibitor constants (Ki) for halothane estimated to be 1.56 and 1. 64 mM,respectively. The gas anesthetic also decreased the overall rate of in vivo metabolism of ketamine (30 mg/kg i. v.) in a concentration-dependent manner. Thus halothane anesthesia by decreasing uptake, distribution, redistribution and metabolism of intramuscularly administered ketamine produced significant prolongation of its pharmacologic action on the central nervous system. Our results imply that concomitant use of inhalational anesthetics may prolong pharmacologic actions of other agents via effects on distribution/redistribution processes as well as on metabolism.", "contents": "Effects of halothane anesthesia on the biodisposition of ketamine in rats. Ketamine, a highly lipophilic drug, was rapidly distributed into highly vascular organs and subsequently redistributed to less well perfused tissues, with concurrent hepatic metabolism and urinary and biliary excretion, after both i. m. and i. v. administration in the rat. Halothane, a potent cardiovascular depressant, was found to prolong the plasma and brain half-life of ketamine (50 mg/kg i.m.) and also increased the duration of ketamine-induced ataxia when the two drugs were administered concomitantly. Halothane anesthesia (0.8% halothane in oxygen) produced a decrease in the rate of uptake and delayed distribution and redistribution of ketamine (50 mg/kg i. m.), while the rate of urinary excretion of ketamine was not significantly altered. Similarly, redistribution of intravenously administered ketamine (30 mg/kg i. v.) was slowed in the presence of halothane. In vitro hepatic microsomal metabolism of ketamine and its principle N-demethylated metabolite, metabolite I, was inhibited noncompetitively by halothane with inhibitor constants (Ki) for halothane estimated to be 1.56 and 1. 64 mM,respectively. The gas anesthetic also decreased the overall rate of in vivo metabolism of ketamine (30 mg/kg i. v.) in a concentration-dependent manner. Thus halothane anesthesia by decreasing uptake, distribution, redistribution and metabolism of intramuscularly administered ketamine produced significant prolongation of its pharmacologic action on the central nervous system. Our results imply that concomitant use of inhalational anesthetics may prolong pharmacologic actions of other agents via effects on distribution/redistribution processes as well as on metabolism."} {"id": "PMID:1263111", "title": "Physiological disposition and biotransformation of (3H) cocaine in acutely and chronically treated rats.", "content": "A sensitive method was developed for the estimation of [3H] cocaine in biological materials. After an injection of 8 mg/kg i.v. in male Wistar rats, peak levels in brain, tissues and plasma occurred within 15 minutes and cocaine disappeared completely from brain and plasma 6 hours postinjection. The T1/2 of cocaine in brain and plasma was 0.4 and 0.3 hour, respectively. No significant differences were observed in the rates of disappearance of cocaine from the subcutaneous site in acute and chronically treated rats after an injection of 20 mg/kg. After a 20 mg/kg s. c. dose, the peak levels of cocaine were attained gradually in 4 hours in brain, tissues and plasma with the exception of heart (0.5 hour) and fat (2 hours). These peak levels shifted from 4 to 2 hours in the chronically treated group. Consistently higher levels of cocaine were found to be sequestered in fat in the chronically treated animals. The T1/2 of cocaine in brain and plasma of chronically treated rats was approximately 1.8 to 2 hours and that in the acutely treated animals, 0.8 to 1 hour. The brain/plasma ratios were also somewhat higher in chronically treated as compared to the acutely treated animals and were indicative of a high affinity of tissue for cocaine. Although cocaine did not persist in brains of acutely treated animals, measurable amounts were shown to persist in brain and other tissues of chronically treated animals long after the disappearance in plasma. Significantly high concentrations of metabolites of cocaine persisted in brain and plasma of acutely and chronically treated animals. No significant differences were observed in the plasma protein binding of cocaine in control, acutely and chronically treated rats. Unchanged cocaine was excreted in very small amounts in rat bile and approximately 36% of the dose (5 mg/kg i. v.) was excreted as metabolites 3.5 hours after injection. Excretion of free cocaine in urine and feces after a 20 mg/kg s. c. dose in acutely and chronically treated rats was 1.2 and 1.5%, respectively. Significantly higher excretion of total radioactivity occurred in feces in the chronic group (35.9%) as compared to the acute group (22.1%). Benzoylecgonine, benzoyl norecgonine, ecgonine methyl ester and ecgonine were identified as urinary metabolites in both acute and chronic animals. In addition, evidence was obtained for the presence of a phenolic metabolite and two other hydroxylated metabolites (with hydroxylation presumably in positions 6 and 7 of the pyrrolidine ring). Implications of these observations with respect to systemic toxicity, the absence of tolerance and physical dependence liability of cocaine are discussed.", "contents": "Physiological disposition and biotransformation of (3H) cocaine in acutely and chronically treated rats. A sensitive method was developed for the estimation of [3H] cocaine in biological materials. After an injection of 8 mg/kg i.v. in male Wistar rats, peak levels in brain, tissues and plasma occurred within 15 minutes and cocaine disappeared completely from brain and plasma 6 hours postinjection. The T1/2 of cocaine in brain and plasma was 0.4 and 0.3 hour, respectively. No significant differences were observed in the rates of disappearance of cocaine from the subcutaneous site in acute and chronically treated rats after an injection of 20 mg/kg. After a 20 mg/kg s. c. dose, the peak levels of cocaine were attained gradually in 4 hours in brain, tissues and plasma with the exception of heart (0.5 hour) and fat (2 hours). These peak levels shifted from 4 to 2 hours in the chronically treated group. Consistently higher levels of cocaine were found to be sequestered in fat in the chronically treated animals. The T1/2 of cocaine in brain and plasma of chronically treated rats was approximately 1.8 to 2 hours and that in the acutely treated animals, 0.8 to 1 hour. The brain/plasma ratios were also somewhat higher in chronically treated as compared to the acutely treated animals and were indicative of a high affinity of tissue for cocaine. Although cocaine did not persist in brains of acutely treated animals, measurable amounts were shown to persist in brain and other tissues of chronically treated animals long after the disappearance in plasma. Significantly high concentrations of metabolites of cocaine persisted in brain and plasma of acutely and chronically treated animals. No significant differences were observed in the plasma protein binding of cocaine in control, acutely and chronically treated rats. Unchanged cocaine was excreted in very small amounts in rat bile and approximately 36% of the dose (5 mg/kg i. v.) was excreted as metabolites 3.5 hours after injection. Excretion of free cocaine in urine and feces after a 20 mg/kg s. c. dose in acutely and chronically treated rats was 1.2 and 1.5%, respectively. Significantly higher excretion of total radioactivity occurred in feces in the chronic group (35.9%) as compared to the acute group (22.1%). Benzoylecgonine, benzoyl norecgonine, ecgonine methyl ester and ecgonine were identified as urinary metabolites in both acute and chronic animals. In addition, evidence was obtained for the presence of a phenolic metabolite and two other hydroxylated metabolites (with hydroxylation presumably in positions 6 and 7 of the pyrrolidine ring). Implications of these observations with respect to systemic toxicity, the absence of tolerance and physical dependence liability of cocaine are discussed."} {"id": "PMID:1263112", "title": "Pharmacokinetics of acetaminophen elimination by anephric patients.", "content": "The pharmacokinetics of acetaminophen elimination were determined in five surgically anephric and five physiologically anephric patients on an interdialysis day, and in three normal adult volunteers. There was no significant difference in the biologic half-life and no apparent difference in the volume of distribution of acetaminophen between the three groups of subjects but the anephrics, unlike the normal subjects, showed pronounced accumulation of acetaminophen glucuronide and sulfate in plasma. The apparent volume of distribution for conjugated acetaminophen is considerably smaller than that for the unmetabolized drug even though neither acetaminophen nor its glucuronide or sulfate is significantly bound to plasma proteins. The results of this study indicate that the kidneys do not contribute significantly to the elimination of acetaminophen in man. Sin ce acetaminophen is eliminated largely by conjugation with glucuronic acid and sulfate, it can be concluded that the kidneys do not contribute significantly to the formation of these metabolites.", "contents": "Pharmacokinetics of acetaminophen elimination by anephric patients. The pharmacokinetics of acetaminophen elimination were determined in five surgically anephric and five physiologically anephric patients on an interdialysis day, and in three normal adult volunteers. There was no significant difference in the biologic half-life and no apparent difference in the volume of distribution of acetaminophen between the three groups of subjects but the anephrics, unlike the normal subjects, showed pronounced accumulation of acetaminophen glucuronide and sulfate in plasma. The apparent volume of distribution for conjugated acetaminophen is considerably smaller than that for the unmetabolized drug even though neither acetaminophen nor its glucuronide or sulfate is significantly bound to plasma proteins. The results of this study indicate that the kidneys do not contribute significantly to the elimination of acetaminophen in man. Sin ce acetaminophen is eliminated largely by conjugation with glucuronic acid and sulfate, it can be concluded that the kidneys do not contribute significantly to the formation of these metabolites."} {"id": "PMID:1263113", "title": "Enhancement of diphenylhydantoin binding by lipid extraction.", "content": "The binding of diphenylhydantoin-14C (DPH-14C) to several purified proteins and a number of tissue fractions from rats and rabbits has been studied by ultrafiltration and dynamic dialysis. In all cases the extent of binding correlated very closely with the protein concentration of the fraction investigated. Although binding to purified proteins varied considerably, binding to whole brain, subcellular fractions, liver, heart and kidney were identical. Skeletal muscle bound significantly less than other tissues. When brain homogenates were extracted with acetone or chloroform-methanol (2:1), the insoluble residue bound considerably greater amounts of DPH-14C per milligram of protein. Binding decreased after incubation with a proteolytic enzyme, but was not influenced by the addition of cations, ethylenediamine tetraacetic acid or ouabain. DPH-3H binding was constant over a large range of DPH concentrations (1 X 10(-10) to 2 X 10(-4)M) with no evidence for saturable or high affinity binding sites. It is suggested that tissue protein binding plays a role in the delayed attainment of adequate serum levels and the pharmacologic action of DPH.", "contents": "Enhancement of diphenylhydantoin binding by lipid extraction. The binding of diphenylhydantoin-14C (DPH-14C) to several purified proteins and a number of tissue fractions from rats and rabbits has been studied by ultrafiltration and dynamic dialysis. In all cases the extent of binding correlated very closely with the protein concentration of the fraction investigated. Although binding to purified proteins varied considerably, binding to whole brain, subcellular fractions, liver, heart and kidney were identical. Skeletal muscle bound significantly less than other tissues. When brain homogenates were extracted with acetone or chloroform-methanol (2:1), the insoluble residue bound considerably greater amounts of DPH-14C per milligram of protein. Binding decreased after incubation with a proteolytic enzyme, but was not influenced by the addition of cations, ethylenediamine tetraacetic acid or ouabain. DPH-3H binding was constant over a large range of DPH concentrations (1 X 10(-10) to 2 X 10(-4)M) with no evidence for saturable or high affinity binding sites. It is suggested that tissue protein binding plays a role in the delayed attainment of adequate serum levels and the pharmacologic action of DPH."} {"id": "PMID:1263114", "title": "The potentiation of barbiturate-induced narcosis by procarbazine.", "content": "Procarbazine (MIH), N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide (NSC-77213), a clinically effective antineoplastic agent, induced sleep in mice at its optimally effective dose (400 mg/kg) and prolongs hexobarbital sleeping times. MIH (400 mg/kg) increased the period of sleep following hexobarbital (100 mg/kg) nearly 10-fold. Nonhypnotic doses of MIH also significantly prolonged hexobarbital-induced sleep. Hexobarbital half-life in plasma was prolonged 6 to 7 times by prior treatment with MIH (400 mg/kg). Liver microsomes from mice treated with MIH exhibited decreased metabolism of the following substrates in vitro: hexobarbital, aminopyrine, ethylmorphine, and aniline. Cytochrome P-450 levels were also decreased by MIH treatment. Maximal decreases in enzyme activity and P-450 content occurred between 4 and 8 hours following treatment. Pretreatment with phenobarbital decreased the effectiveness of MIH to prolong hexobarbital sleeping times while pretreatment with SKF 525A added to the potentiating effect of MIH. Two major metabolites of MIH had neither central nervous system hypnotic effect nor inhibited hepatic microsomal mixed-function oxidases. Therefore, MIH potentiation of hexobarbital-induces sleep is probably due both to its direct hypnotic effect and inhibition of mixed-function oxidase activity.", "contents": "The potentiation of barbiturate-induced narcosis by procarbazine. Procarbazine (MIH), N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide (NSC-77213), a clinically effective antineoplastic agent, induced sleep in mice at its optimally effective dose (400 mg/kg) and prolongs hexobarbital sleeping times. MIH (400 mg/kg) increased the period of sleep following hexobarbital (100 mg/kg) nearly 10-fold. Nonhypnotic doses of MIH also significantly prolonged hexobarbital-induced sleep. Hexobarbital half-life in plasma was prolonged 6 to 7 times by prior treatment with MIH (400 mg/kg). Liver microsomes from mice treated with MIH exhibited decreased metabolism of the following substrates in vitro: hexobarbital, aminopyrine, ethylmorphine, and aniline. Cytochrome P-450 levels were also decreased by MIH treatment. Maximal decreases in enzyme activity and P-450 content occurred between 4 and 8 hours following treatment. Pretreatment with phenobarbital decreased the effectiveness of MIH to prolong hexobarbital sleeping times while pretreatment with SKF 525A added to the potentiating effect of MIH. Two major metabolites of MIH had neither central nervous system hypnotic effect nor inhibited hepatic microsomal mixed-function oxidases. Therefore, MIH potentiation of hexobarbital-induces sleep is probably due both to its direct hypnotic effect and inhibition of mixed-function oxidase activity."} {"id": "PMID:1263115", "title": "Effects of alcohol, chlordiazepoxide, cocaine and pentobarbital on responding maintained under fixed-interval schedules of food or shock presentation.", "content": "Responding by three squirrel monkeys was maintained under multiple-and single-component 5-minute fixed-interval (FI) schedules of either food or electric shock presentation. Under the multiple schedule, a response after 5 minutes had elapsed produced either food or shock depending on the prevailing stimulus conditions; single-component FI schedules maintained responding either by food or shock presentation alone. Responding under either the food or the shock schedules was positively accelerated throughout each FI. During certain phases of the experiment, overall response rates maintained by foor were comparable to those maintained by shock. Alcohol (1.0-3.0 g/kg), chlordiazepoxide (1.0-10.0 mg/kg) and pentobarbital (1.0-10.0 mg/kg) increased responding maintained by food but decreased responding maintained by shock. These effects were obtained under both the multiple- and single-component schedules. Low to intermediate doses of cocaine (0.1-1.0 mg/kg) increased responding maintained by either food or shock, whereas higher doses (3.0 mg/kg) generally decreased responding under these conditions. The effects of chlordiazepoxide were also studied with one monkey when response rates maintained by food or shock were equal, when rates of food-maintained responding were lower than those maintained by shock and, finally, when rates of responding maintained by food were higher than those maintained by shock. Under all of these conditions, chlordiazepoxide increased food-maintained response rates and decreased responding maintained by shock presentation.", "contents": "Effects of alcohol, chlordiazepoxide, cocaine and pentobarbital on responding maintained under fixed-interval schedules of food or shock presentation. Responding by three squirrel monkeys was maintained under multiple-and single-component 5-minute fixed-interval (FI) schedules of either food or electric shock presentation. Under the multiple schedule, a response after 5 minutes had elapsed produced either food or shock depending on the prevailing stimulus conditions; single-component FI schedules maintained responding either by food or shock presentation alone. Responding under either the food or the shock schedules was positively accelerated throughout each FI. During certain phases of the experiment, overall response rates maintained by foor were comparable to those maintained by shock. Alcohol (1.0-3.0 g/kg), chlordiazepoxide (1.0-10.0 mg/kg) and pentobarbital (1.0-10.0 mg/kg) increased responding maintained by food but decreased responding maintained by shock. These effects were obtained under both the multiple- and single-component schedules. Low to intermediate doses of cocaine (0.1-1.0 mg/kg) increased responding maintained by either food or shock, whereas higher doses (3.0 mg/kg) generally decreased responding under these conditions. The effects of chlordiazepoxide were also studied with one monkey when response rates maintained by food or shock were equal, when rates of food-maintained responding were lower than those maintained by shock and, finally, when rates of responding maintained by food were higher than those maintained by shock. Under all of these conditions, chlordiazepoxide increased food-maintained response rates and decreased responding maintained by shock presentation."} {"id": "PMID:1263116", "title": "The effects of phencyclidine, ketamine, delta-amphetamine and pentobarbital on schedule-controlled behavior in the mouse.", "content": "The response of mice of breaking a light beam onto a photocell was programmed to produce food according to a multiple schedule with alternating 30-response fixed ratio, 300-second fixed interval (FR-30 FI-300 sec) components. Training was standardized for all mice, and stable patterns of responding that were similar to those described for other species and responses under this schedule developed quickly. The effects of pentobaribtal, delta-amphetamine, phencyclidine and ketamine were studied. At some dose, each of the four drugs produced an increase in rate of responding; the increase was proportionately greater at low rates of responding than at higher rates. At some dose range, delta-amphetamine, ketamine and phencyclidine produced dose-related increases in FI average rates were to 1.83, 1.25 and 1.32 times the control rate for delta-amphetamine (1 mg/kg), ketamine (100 mg/kg) and phencyclidine (3 mg/kg), respectively. Phencyclidine and ketamine thus showed some \"amphetamine-like\" effects in the mouse. Pentobarbital increased (1.25 times the control rate) both the FR and FI response rates at a dose of 3 mg/kg. Higher doses of pentobarbital progressively decreased both FR and FI response rates in a parallel fashion.", "contents": "The effects of phencyclidine, ketamine, delta-amphetamine and pentobarbital on schedule-controlled behavior in the mouse. The response of mice of breaking a light beam onto a photocell was programmed to produce food according to a multiple schedule with alternating 30-response fixed ratio, 300-second fixed interval (FR-30 FI-300 sec) components. Training was standardized for all mice, and stable patterns of responding that were similar to those described for other species and responses under this schedule developed quickly. The effects of pentobaribtal, delta-amphetamine, phencyclidine and ketamine were studied. At some dose, each of the four drugs produced an increase in rate of responding; the increase was proportionately greater at low rates of responding than at higher rates. At some dose range, delta-amphetamine, ketamine and phencyclidine produced dose-related increases in FI average rates were to 1.83, 1.25 and 1.32 times the control rate for delta-amphetamine (1 mg/kg), ketamine (100 mg/kg) and phencyclidine (3 mg/kg), respectively. Phencyclidine and ketamine thus showed some \"amphetamine-like\" effects in the mouse. Pentobarbital increased (1.25 times the control rate) both the FR and FI response rates at a dose of 3 mg/kg. Higher doses of pentobarbital progressively decreased both FR and FI response rates in a parallel fashion."} {"id": "PMID:1263117", "title": "A positive inotropic effect of propranolol on the canine myocardium: a presynaptic effect.", "content": "Administration of propranolol directly into the anterior descending branch of the left coronary artery (LAD) resulted in a localized increase in myocardial contractile force in the area of the left ventricle perfused by the LAD. The onset of the positive inotropic response occurred within 30 seconds after drug administration with a duration of action of approximately 8 minutes and was associated with a significant increase in the coronary sinus/arterial ratio of norepinephrine. Contractile force in an area of the left ventricle perfused by the circumflex artery decreased concomitantly with the characteristic negative chronotropic action of propranolol. Pretreatment with reserpine abolished the positive inotropic effect of propranolol while ganglionic blockade with hexamethonium failed to alter the character of the response. Imipramine pretreatment not only blocked the positive inotropic effect of propranolol but resulted in an exaggerated negative inotropic effect in both areas of the left ventricle along with a significant fall in systemic arterial blood pressure. The data demonstrate that propranolol can evoke the release of norepinephrine from cardiac adrenergic nerve endings and raise the possibility that propranolol may be taken up by the amine uptake system.", "contents": "A positive inotropic effect of propranolol on the canine myocardium: a presynaptic effect. Administration of propranolol directly into the anterior descending branch of the left coronary artery (LAD) resulted in a localized increase in myocardial contractile force in the area of the left ventricle perfused by the LAD. The onset of the positive inotropic response occurred within 30 seconds after drug administration with a duration of action of approximately 8 minutes and was associated with a significant increase in the coronary sinus/arterial ratio of norepinephrine. Contractile force in an area of the left ventricle perfused by the circumflex artery decreased concomitantly with the characteristic negative chronotropic action of propranolol. Pretreatment with reserpine abolished the positive inotropic effect of propranolol while ganglionic blockade with hexamethonium failed to alter the character of the response. Imipramine pretreatment not only blocked the positive inotropic effect of propranolol but resulted in an exaggerated negative inotropic effect in both areas of the left ventricle along with a significant fall in systemic arterial blood pressure. The data demonstrate that propranolol can evoke the release of norepinephrine from cardiac adrenergic nerve endings and raise the possibility that propranolol may be taken up by the amine uptake system."} {"id": "PMID:1263118", "title": "Effects of disopyramide phosphate on ventricular arrhythmias in experimental myocardial infarction.", "content": "A myocardial infarction model in which infarction is the result of an occluding thrombus was used to evaluate the effectiveness of disopyramide phosphate (DP) in abolishing postinfarction ventricular arrhythmis. Two types of ventricular arrhythmias were observed, rapid multifocal arrhythmias. and slow unifocal rhythms. DP, in doses of 5 mg/kg, were effective against slow ventricular tachycardia. The time course of action varied with the type of rhythm present. Conversion of the slow ventricular tachycardia usually occurred within a minute whereas abolition of the rapid ventricular tachycardia took 5 to 10 minutes. Effective arrhythmia control could be maintained by a bolus dose (3 mg/kg) followed by a constant infusion at a rate of 0.2 mg/kg/min. DP had minimal effects on arterial blood pressure at antiarrhythmic doses. The drug had significant hypotensive effects if infused at rates greater than 2 mg/kg/min. However, the hypotensive effect was always transient at doses of 5 mg/kg or less. DP produced significant changes in the lead II electrocardiogram. At doses of 5 mg/kg, the drug significantly increased the P-R and Q-Tc intervals and increased the QRS duration. The drug slowed conduction through all parts of the conducting system to approximately the same degree with perhaps a slightly greater slowing through the atrioventricular node. However, the changes observed were never more than 20%", "contents": "Effects of disopyramide phosphate on ventricular arrhythmias in experimental myocardial infarction. A myocardial infarction model in which infarction is the result of an occluding thrombus was used to evaluate the effectiveness of disopyramide phosphate (DP) in abolishing postinfarction ventricular arrhythmis. Two types of ventricular arrhythmias were observed, rapid multifocal arrhythmias. and slow unifocal rhythms. DP, in doses of 5 mg/kg, were effective against slow ventricular tachycardia. The time course of action varied with the type of rhythm present. Conversion of the slow ventricular tachycardia usually occurred within a minute whereas abolition of the rapid ventricular tachycardia took 5 to 10 minutes. Effective arrhythmia control could be maintained by a bolus dose (3 mg/kg) followed by a constant infusion at a rate of 0.2 mg/kg/min. DP had minimal effects on arterial blood pressure at antiarrhythmic doses. The drug had significant hypotensive effects if infused at rates greater than 2 mg/kg/min. However, the hypotensive effect was always transient at doses of 5 mg/kg or less. DP produced significant changes in the lead II electrocardiogram. At doses of 5 mg/kg, the drug significantly increased the P-R and Q-Tc intervals and increased the QRS duration. The drug slowed conduction through all parts of the conducting system to approximately the same degree with perhaps a slightly greater slowing through the atrioventricular node. However, the changes observed were never more than 20%"} {"id": "PMID:1263119", "title": "Nicotine-like actions of cis-metanicotine and trans-metanicotine.", "content": "The actions of the cis- and trans-isomers of metanicotine were observed on isolated rabbit aortic strips and ileal segments. The data are interpreted as showing a nicotine-like action on these preparations for both cis-metanicotine and trans-metanicotine. This hypothesis is supported in part by the demonstration that the action of the metanicotine isomers was affected by hexamethonium, cocaine, phenotolamine, reserpine and atropine in a manner similar to that previously seen in studies with nicotine. In dose-response studies on the aortic strip, trans-metanicotine was significantly less active than nicotine. cis-Metanicotine in turn was less active than trans-metanicotine and nicotine. Additionally, four pyridino compounds, 3-pyridylacet acid, N-(3 pyridlyacetyl) glycine, nicotinuric acid and trans-4-(3-pyridyl)-3-butenoic acid, were tested for both agonist and antagonist activity. No stimulatory activity was found with these compounds in either the aortic strip or ileal preparations. In aortic strip preparations, pretreatment with either 3-pyridylacetic acid or N-(3-pyridylacetyl) glycine provided a moderate to marked reduction in the contractile response to trans-metanicotine, whereas pretreatment with trans-4-(3-pyridyl)-3-butenoic acid caused a slight reduction.", "contents": "Nicotine-like actions of cis-metanicotine and trans-metanicotine. The actions of the cis- and trans-isomers of metanicotine were observed on isolated rabbit aortic strips and ileal segments. The data are interpreted as showing a nicotine-like action on these preparations for both cis-metanicotine and trans-metanicotine. This hypothesis is supported in part by the demonstration that the action of the metanicotine isomers was affected by hexamethonium, cocaine, phenotolamine, reserpine and atropine in a manner similar to that previously seen in studies with nicotine. In dose-response studies on the aortic strip, trans-metanicotine was significantly less active than nicotine. cis-Metanicotine in turn was less active than trans-metanicotine and nicotine. Additionally, four pyridino compounds, 3-pyridylacet acid, N-(3 pyridlyacetyl) glycine, nicotinuric acid and trans-4-(3-pyridyl)-3-butenoic acid, were tested for both agonist and antagonist activity. No stimulatory activity was found with these compounds in either the aortic strip or ileal preparations. In aortic strip preparations, pretreatment with either 3-pyridylacetic acid or N-(3-pyridylacetyl) glycine provided a moderate to marked reduction in the contractile response to trans-metanicotine, whereas pretreatment with trans-4-(3-pyridyl)-3-butenoic acid caused a slight reduction."} {"id": "PMID:1263120", "title": "Computer simulation of local anesthetic effects using a mathematical model of myelinated nerve.", "content": "A mathematical model of myelinated axon was programmed for digital computer solution of the consequences of the conduction characteristics when the model membrane was affected by local anesthetics simulated by alteration of the ionic conductance parameter. The effects of tetrodotoxin on impulse conduction were studied in detail by means of a systematic reduction in sodium conductance in 1 to 10 nodes of Ranvier. Rhis technique simulates the method used experimentally and clinically to achieve a conduction block with the circumscribed application of local anesthetics to segments of nerve axons or nerve trunks. The analysis of the tetrodotoxin \"dose-response\" relationships revealed the fact that the model myelinated axon could support three types of conduction when depressed by this drug. One type of conduction of a subnormal impulse at the nodes of Ranvier; a second is characterized by a form of decremental conduction in which the rate of decrement of the nodal impulse is linear with distance. The third type is a second form of decremental conduction which is exponential in configuration and is seen when the g(Na) at the nodes of Ranvier is reduced to less than 27% of normal. Parallel experiments were performed to simulate the effects of lidocaine and some significant differences were observed. Analysis of the action potentials within the internodel region suggests that, although immune to drug action in the model, the internodal segment affects the generation of action potentials at the nodes. A commentary is presented on the limitations of the model as it reflects known pharmacologic relationships in real myelinated axons.", "contents": "Computer simulation of local anesthetic effects using a mathematical model of myelinated nerve. A mathematical model of myelinated axon was programmed for digital computer solution of the consequences of the conduction characteristics when the model membrane was affected by local anesthetics simulated by alteration of the ionic conductance parameter. The effects of tetrodotoxin on impulse conduction were studied in detail by means of a systematic reduction in sodium conductance in 1 to 10 nodes of Ranvier. Rhis technique simulates the method used experimentally and clinically to achieve a conduction block with the circumscribed application of local anesthetics to segments of nerve axons or nerve trunks. The analysis of the tetrodotoxin \"dose-response\" relationships revealed the fact that the model myelinated axon could support three types of conduction when depressed by this drug. One type of conduction of a subnormal impulse at the nodes of Ranvier; a second is characterized by a form of decremental conduction in which the rate of decrement of the nodal impulse is linear with distance. The third type is a second form of decremental conduction which is exponential in configuration and is seen when the g(Na) at the nodes of Ranvier is reduced to less than 27% of normal. Parallel experiments were performed to simulate the effects of lidocaine and some significant differences were observed. Analysis of the action potentials within the internodel region suggests that, although immune to drug action in the model, the internodal segment affects the generation of action potentials at the nodes. A commentary is presented on the limitations of the model as it reflects known pharmacologic relationships in real myelinated axons."} {"id": "PMID:1263121", "title": "An investigation of the natriuretic, antidiuretic and oxytocic actions of neurohypophysial hormones and related peptides: delineation of separate mechanisms of action and assessment of molecular requirements.", "content": "The substitution of the 4-glutamine of oxytocin by a lipophilic aliphatic amino acid leucine yields [4-Leu] oxytocin which possesses natriuretic-diuretic anti-arginine-vasopressin (anti-ADH) activities. Alkyl substitutions of the beta-carbon of the 1 half-cystine of oxytocin yield a series of antioxytocin analogs which inhibit the uterotonic response to oxytocin. In this paper, the results of our further investigations on the molecular requirements for natriuretic, anti-ADH and antioxytocic activities of these peptides are reported. A total of 12 analogs of oxytocin and lysine-vasopressin (LVP) with leucine and/or beta-carbon alkyl substitutions were studied. Our findings reveal that the effect of 4-leucine substitution may not be to enhance the natriuretic activity but rather to abolish the antidiuretic activity of oxytocin. The lack of antidiuretic activity of these 4-leucine analogs makes it possible to unmask the intrinsic natriuretic activity of these peptides at the high dose level. Structure-activity correlations suggest that the oxytocin molecule may be the optimal requirement for natriuretic activity of these peptides. Substitution of 4-glutamine by lipophilic aromatic phenylalanine yields [4-Phe] oxytocin which possesses anti-ADH activity with little or no natriuretic activity. The \"hybrid\" antioxytocin and anti-ADH molecules, beta-carbon alkyl and 4-leucine substituted analogs did not possess enhanced antihormone activity. Although they had antioxytocic and antipressor activities, they were less potent than their respective singly alkyl substituted analogs. Furthermore, they had no demonstrable anti-ADH activity. The single alkyl substituted oxytocin and LVP also had no anti-ADH activity. It therefore appears that beta-carbon alkyl substitution had different effects on activities depending on the morphological features and the functions of the target cell. In target cells of contractile smooth muscles (uterus and vascular), the alkyl substituted analogs had no intrinsic activity but retained a relatively high receptor affinity to become effective antagonists to the natural hormone. On the other hand, in target cells of the renal tubule which are noncontractile epithelial cells, both intrinsic activity and receptor affinity were reduced or abolished. Thus none of these alkyl substituted analogs possessed more than very slight antidiuretic activity, and none had any natriuretic or anti-ADH activity.", "contents": "An investigation of the natriuretic, antidiuretic and oxytocic actions of neurohypophysial hormones and related peptides: delineation of separate mechanisms of action and assessment of molecular requirements. The substitution of the 4-glutamine of oxytocin by a lipophilic aliphatic amino acid leucine yields [4-Leu] oxytocin which possesses natriuretic-diuretic anti-arginine-vasopressin (anti-ADH) activities. Alkyl substitutions of the beta-carbon of the 1 half-cystine of oxytocin yield a series of antioxytocin analogs which inhibit the uterotonic response to oxytocin. In this paper, the results of our further investigations on the molecular requirements for natriuretic, anti-ADH and antioxytocic activities of these peptides are reported. A total of 12 analogs of oxytocin and lysine-vasopressin (LVP) with leucine and/or beta-carbon alkyl substitutions were studied. Our findings reveal that the effect of 4-leucine substitution may not be to enhance the natriuretic activity but rather to abolish the antidiuretic activity of oxytocin. The lack of antidiuretic activity of these 4-leucine analogs makes it possible to unmask the intrinsic natriuretic activity of these peptides at the high dose level. Structure-activity correlations suggest that the oxytocin molecule may be the optimal requirement for natriuretic activity of these peptides. Substitution of 4-glutamine by lipophilic aromatic phenylalanine yields [4-Phe] oxytocin which possesses anti-ADH activity with little or no natriuretic activity. The \"hybrid\" antioxytocin and anti-ADH molecules, beta-carbon alkyl and 4-leucine substituted analogs did not possess enhanced antihormone activity. Although they had antioxytocic and antipressor activities, they were less potent than their respective singly alkyl substituted analogs. Furthermore, they had no demonstrable anti-ADH activity. The single alkyl substituted oxytocin and LVP also had no anti-ADH activity. It therefore appears that beta-carbon alkyl substitution had different effects on activities depending on the morphological features and the functions of the target cell. In target cells of contractile smooth muscles (uterus and vascular), the alkyl substituted analogs had no intrinsic activity but retained a relatively high receptor affinity to become effective antagonists to the natural hormone. On the other hand, in target cells of the renal tubule which are noncontractile epithelial cells, both intrinsic activity and receptor affinity were reduced or abolished. Thus none of these alkyl substituted analogs possessed more than very slight antidiuretic activity, and none had any natriuretic or anti-ADH activity."} {"id": "PMID:1263122", "title": "Mechanism of action of cobra cardiotoxin in the skeletal muscle.", "content": "Cobra cardiotoxin (CTX) is a potent polypeptide in inducing irreversible contracture of the chick biventer cervicis muscle. this polypeptide is about 2000 times more potent than caffeine in inducing contracture of this muscle preparation but the rate of CTX contracture is slower. Studies on the interaction on CTX with divalent cations showed that low Ca0++ (10(-31-2 mM)-Krebs' enhanced markedly while ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid-Krebs' or high Ca++ (12 mM) inhibited completely CTX contracture; 10 mM Mg++ enhanced but 20 mM Mg++ or 10 mM Zn++ inhibited CTX contracture. Neither Na+ nor tetrodotoxin affected CTX contracture. Comparison of CTX and caffeine contracture showed that ethylenediamine tetraacetic acid (1 mM) and Mn++ (5 mM) inhibited CTX contracture completely but inhibited caffeine contracture only partially; procaine did not inhibit CTX contracture but inhibited caffeine contracture competitively; by contrast, N-ethylmaleimide inhibited CTX but not caffeine contracture. Neither caffeine nor K+ contracture was inhibited by 12 mM Ca++. CTX could induce contracture in the depolarized muscle and the muscle with T-tubule destroyed or closed, whereas K+ failed to induce contracture in the latter. Caffeine contracture was inhibited in the muscle with a previous elicitation of CTX contracture. This antagonistic effect of CTX could be prevented by calcium. Moreover, CTX increased both 45Ca++ efflux and 45Ca++ uptake. Both Zn++ (0.6 mM) and Mg++ (10 mM) but not protamine and polylysine mimicked CTX to increase 45 Ca++ uptake. Zn++ (0.6mM) was also found to be effective in replacing Ca0++ to induce CTX contracture in 10(-6) M Ca0++. CTX increased Ca and Na but decreased K contents of the muscle. The binding of radioactive iodinated CTX was inhibited not only by unlabeled CTX but also by 10mM Ca++. All of these findings suggest that CTX may affect a membrane calcium binding site and may induce contracture by releasing the membrane calcium rather than by increasing Na+ permeability of the muscle membrane.", "contents": "Mechanism of action of cobra cardiotoxin in the skeletal muscle. Cobra cardiotoxin (CTX) is a potent polypeptide in inducing irreversible contracture of the chick biventer cervicis muscle. this polypeptide is about 2000 times more potent than caffeine in inducing contracture of this muscle preparation but the rate of CTX contracture is slower. Studies on the interaction on CTX with divalent cations showed that low Ca0++ (10(-31-2 mM)-Krebs' enhanced markedly while ethylene glycol bis (beta-aminoethyl ether)-N,N'-tetraacetic acid-Krebs' or high Ca++ (12 mM) inhibited completely CTX contracture; 10 mM Mg++ enhanced but 20 mM Mg++ or 10 mM Zn++ inhibited CTX contracture. Neither Na+ nor tetrodotoxin affected CTX contracture. Comparison of CTX and caffeine contracture showed that ethylenediamine tetraacetic acid (1 mM) and Mn++ (5 mM) inhibited CTX contracture completely but inhibited caffeine contracture only partially; procaine did not inhibit CTX contracture but inhibited caffeine contracture competitively; by contrast, N-ethylmaleimide inhibited CTX but not caffeine contracture. Neither caffeine nor K+ contracture was inhibited by 12 mM Ca++. CTX could induce contracture in the depolarized muscle and the muscle with T-tubule destroyed or closed, whereas K+ failed to induce contracture in the latter. Caffeine contracture was inhibited in the muscle with a previous elicitation of CTX contracture. This antagonistic effect of CTX could be prevented by calcium. Moreover, CTX increased both 45Ca++ efflux and 45Ca++ uptake. Both Zn++ (0.6 mM) and Mg++ (10 mM) but not protamine and polylysine mimicked CTX to increase 45 Ca++ uptake. Zn++ (0.6mM) was also found to be effective in replacing Ca0++ to induce CTX contracture in 10(-6) M Ca0++. CTX increased Ca and Na but decreased K contents of the muscle. The binding of radioactive iodinated CTX was inhibited not only by unlabeled CTX but also by 10mM Ca++. All of these findings suggest that CTX may affect a membrane calcium binding site and may induce contracture by releasing the membrane calcium rather than by increasing Na+ permeability of the muscle membrane."} {"id": "PMID:1263123", "title": "Digoxin toxicity: primary sites of drug action on the sympathetic nervous system.", "content": "Increases and decreases in sympathetic nerve activity have been reported to accompany digitalis-induced arrhythmias. These effects may result from drug action on various sites such as the central nervous system, ganglia, chemoreceptor or baroreceptor afferent fibers or peripheral efferent nerve fibers. The relative importance of each possible site of drug action has not been clarified. To define the involvement of some of these sites, digoxin was administered intravenously to cats in order to study its effects on activity of preganglionic splanchnic or postganglionic inferior cardiac nerves in the presence or absence of chemoreceptor and baroreceptor reflexes. In cats with intact reflexes, arrhythmic doses of digoxin had diverse effects on postganglionic activity. In some cats digoxin increased activity and in others it decreased activity. In contrast, digoxin consistently caused large progressive increases in postganglionic activity when baroreceptors and chemoreceptors had been denervated. Digoxin inhibited preganglionic nerve activity only in cats with intact reflexes but had no effect in those without chemoreceptor and baroreceptor reflexes. Thus, the afferent component of the baroreceptor reflex is the apparent site of digoxin-induced inhibition. Digoxin produced increases in activity above control only in postganglionic nerves. This finding suggests that digoxin acts on the ganglion to increase sympathetic activity. Digoxin had no discernible effect on preganglionic activity when baroreceptor and chemoreceptor afferent input had been eliminated. To test further for any subliminal drug effect in the brain, effects of intravenously administered digoxin were observed on centrally evoked submaximal responses in the splanchnic nerve. Lethal doses of digoxin had no effect on responses evoked from the medulla or the hypothalamus. Therefore, these data are not consistent with the hypothesis that a primary site of drug action is in the central nervous system. Instead, the data suggest that neural effects of digoxin result primarily from drug actions within the peripheral autonomic nervous system on sites such as the ganglion and peripheral afferent components of the baroreceptor reflex.", "contents": "Digoxin toxicity: primary sites of drug action on the sympathetic nervous system. Increases and decreases in sympathetic nerve activity have been reported to accompany digitalis-induced arrhythmias. These effects may result from drug action on various sites such as the central nervous system, ganglia, chemoreceptor or baroreceptor afferent fibers or peripheral efferent nerve fibers. The relative importance of each possible site of drug action has not been clarified. To define the involvement of some of these sites, digoxin was administered intravenously to cats in order to study its effects on activity of preganglionic splanchnic or postganglionic inferior cardiac nerves in the presence or absence of chemoreceptor and baroreceptor reflexes. In cats with intact reflexes, arrhythmic doses of digoxin had diverse effects on postganglionic activity. In some cats digoxin increased activity and in others it decreased activity. In contrast, digoxin consistently caused large progressive increases in postganglionic activity when baroreceptors and chemoreceptors had been denervated. Digoxin inhibited preganglionic nerve activity only in cats with intact reflexes but had no effect in those without chemoreceptor and baroreceptor reflexes. Thus, the afferent component of the baroreceptor reflex is the apparent site of digoxin-induced inhibition. Digoxin produced increases in activity above control only in postganglionic nerves. This finding suggests that digoxin acts on the ganglion to increase sympathetic activity. Digoxin had no discernible effect on preganglionic activity when baroreceptor and chemoreceptor afferent input had been eliminated. To test further for any subliminal drug effect in the brain, effects of intravenously administered digoxin were observed on centrally evoked submaximal responses in the splanchnic nerve. Lethal doses of digoxin had no effect on responses evoked from the medulla or the hypothalamus. Therefore, these data are not consistent with the hypothesis that a primary site of drug action is in the central nervous system. Instead, the data suggest that neural effects of digoxin result primarily from drug actions within the peripheral autonomic nervous system on sites such as the ganglion and peripheral afferent components of the baroreceptor reflex."} {"id": "PMID:1263124", "title": "Effect of age on the cardiotoxic action of digitalis.", "content": "The cardiotoxic effect of ouabain was explored in rabbits at different ages. The dose of ouabain necessary to produce ventricular tachycardia and death in 1-to 4-week-old rabbits was significantly greater than that required in older animals. In the 1 to 3-week-old animals, ventricular fibrillation occurred only once whereas in animals older than 3 weeks, fibrillation occurred in 23 of 31 animals. A similar pattern of sensitivity to ouabain was observed in bilaterally vagotomized animals. Neither the initial heart rate nor the potassium content of the ventricles in the different age groups appeared to have any influence on the change in the cardiotoxic dose of ouabain. Heart weight increased during the interval when the occurrence of fibrillation increased but it may not fully explain the alteration in the mode of death since fibrillation occurred in some of the younger animals with bilateral vagotomy before the heart weight increased. The catecholamine content of ventricles from 4-to 12-week-old rabbits was significantly greater than that in 1- or 3-week-old rabbits. The age-dependent decrease in the dose of ouabain necessary to produce ventricular tachycardia, ventricular fibrillation and death appeared to be associated with an increase oof ventricular norepinephrine content, although other factors may also play an important part in this response.", "contents": "Effect of age on the cardiotoxic action of digitalis. The cardiotoxic effect of ouabain was explored in rabbits at different ages. The dose of ouabain necessary to produce ventricular tachycardia and death in 1-to 4-week-old rabbits was significantly greater than that required in older animals. In the 1 to 3-week-old animals, ventricular fibrillation occurred only once whereas in animals older than 3 weeks, fibrillation occurred in 23 of 31 animals. A similar pattern of sensitivity to ouabain was observed in bilaterally vagotomized animals. Neither the initial heart rate nor the potassium content of the ventricles in the different age groups appeared to have any influence on the change in the cardiotoxic dose of ouabain. Heart weight increased during the interval when the occurrence of fibrillation increased but it may not fully explain the alteration in the mode of death since fibrillation occurred in some of the younger animals with bilateral vagotomy before the heart weight increased. The catecholamine content of ventricles from 4-to 12-week-old rabbits was significantly greater than that in 1- or 3-week-old rabbits. The age-dependent decrease in the dose of ouabain necessary to produce ventricular tachycardia, ventricular fibrillation and death appeared to be associated with an increase oof ventricular norepinephrine content, although other factors may also play an important part in this response."} {"id": "PMID:1263125", "title": "Effects of 6-hydroxydopa on noradrenergic neurons in developing rat brain.", "content": "The temporal sequence of changes in norepinephrine (NE) levels in various regions of brains of control and 6-hydroxydopa (6-OHDOPA)-treated rats was determined. It was found that 6-OHDOPA (60 mug/g i.p., three doses, 48-hour intervals), when administered from birth, markedly altered the NE content of various brain regions during the following 8-week period. In telencephalic regions, such as the neocortex and hippocampus, NE levels (micrograms per tissue) increased dramatically from birth in saline-treated rats, while NE was depressed by 55 to 85% in 6-OHDOPA animals. Studies for measuring the uptake of 3H-NE (2 X 10(-7) M) by synaptosomes isolated from the neocortex showed that uptake, was reduced by approximately 40% at 2, 5 and 52 weeks of age. Therefore, it appears that 6-OHDOPA is able to permanently impair the ontogenetic development of noradrenergic neurons in regions supplied by the dorsal noradrenergic bundle. In contrast to these effects, NE levels in the cerebellum were elevated 2-fold in 6-OHDOPA-treated rats of 8 weeks, postnatal age. Uptake was not similarly increased, indicating that the elevation in NE was not due to an increase in the number of nerve endings, but rather to an increase in the intraneuronal storage depots of NE. In the hypothalamus NE levels were not dramatically altered, while uptake was reduced by about 40% up to 1 year of age. Application of Michaelis-Menten kinetics indicated a decrease in the Vmax for 3H-NE uptake in the hypothalamus of 6-OHDOPA (60 mug/g i.p., two doses, 48-hour intervals from birth)-treated rats, sacrificed at 6 months of age. The pons-medulla and midbrain regions showed moderate increases in NE levels at 5 and 8 weeks. Uptake 1 was not increased in the pons-medulla at any time, and the Vmax remained unchanged when measured in rats at 6 months of age. It is apparent that 6-OHDOPA is capable of altering the ontogenesis of noradrenergic neurons and that the effects on development are different in different areas of the brain.", "contents": "Effects of 6-hydroxydopa on noradrenergic neurons in developing rat brain. The temporal sequence of changes in norepinephrine (NE) levels in various regions of brains of control and 6-hydroxydopa (6-OHDOPA)-treated rats was determined. It was found that 6-OHDOPA (60 mug/g i.p., three doses, 48-hour intervals), when administered from birth, markedly altered the NE content of various brain regions during the following 8-week period. In telencephalic regions, such as the neocortex and hippocampus, NE levels (micrograms per tissue) increased dramatically from birth in saline-treated rats, while NE was depressed by 55 to 85% in 6-OHDOPA animals. Studies for measuring the uptake of 3H-NE (2 X 10(-7) M) by synaptosomes isolated from the neocortex showed that uptake, was reduced by approximately 40% at 2, 5 and 52 weeks of age. Therefore, it appears that 6-OHDOPA is able to permanently impair the ontogenetic development of noradrenergic neurons in regions supplied by the dorsal noradrenergic bundle. In contrast to these effects, NE levels in the cerebellum were elevated 2-fold in 6-OHDOPA-treated rats of 8 weeks, postnatal age. Uptake was not similarly increased, indicating that the elevation in NE was not due to an increase in the number of nerve endings, but rather to an increase in the intraneuronal storage depots of NE. In the hypothalamus NE levels were not dramatically altered, while uptake was reduced by about 40% up to 1 year of age. Application of Michaelis-Menten kinetics indicated a decrease in the Vmax for 3H-NE uptake in the hypothalamus of 6-OHDOPA (60 mug/g i.p., two doses, 48-hour intervals from birth)-treated rats, sacrificed at 6 months of age. The pons-medulla and midbrain regions showed moderate increases in NE levels at 5 and 8 weeks. Uptake 1 was not increased in the pons-medulla at any time, and the Vmax remained unchanged when measured in rats at 6 months of age. It is apparent that 6-OHDOPA is capable of altering the ontogenesis of noradrenergic neurons and that the effects on development are different in different areas of the brain."} {"id": "PMID:1263126", "title": "Ethanol effects on muscle spindle afferent activity and spinal reflexes.", "content": "The effects of ethanol on muscle spindle afferent activity and on the mono- and polysynaptic reflexes were examined in cats. Ethanol was administered incrementally as intravenous infusions of 0.7 g/kg of ethanol 30 minutes apart; mean arterial blood alcohol concentrations reached 30 minutes after the first and fourth infusions were 1.1 and 3.8 mg/ml, respectively. Ethanol produced modest, dose-related increases in the afferent activity from muscle spindles in spinal- and pentobarbital-anesthetized cats. Mean phasic and static discharge frequencies were both increased approximately 10 impulses/sec after infusions of a total of 2.8 g/kg. In unanesthetized animals, comparable blood levels of ethanol were associated with mild to marked motor incoordination. The mean amplitudes of the mono- and polysnaptic reflexes in spinal animals, elicited with supramaximal single shocks to the muscle nerve, were depressed to 92 and 84% of control levels, respectively, after 0.7 g/kg and continued to fall to 50 and 60% of control levels after 2.8 g/kg of ethanol. Ethanol failed to depress preferentially polysynaptic reflexes. It is concluded that the spindle afferent excitation was involved in the motor effects of ethanol but that it was insufficient to explain fully the skeletomotor alterations produced by ethanol; rather, ethanol actions at peripheral and spinal and, perhaps, supraspinal sites all appear to be involved in ethanol-induced impairment of motor function.", "contents": "Ethanol effects on muscle spindle afferent activity and spinal reflexes. The effects of ethanol on muscle spindle afferent activity and on the mono- and polysynaptic reflexes were examined in cats. Ethanol was administered incrementally as intravenous infusions of 0.7 g/kg of ethanol 30 minutes apart; mean arterial blood alcohol concentrations reached 30 minutes after the first and fourth infusions were 1.1 and 3.8 mg/ml, respectively. Ethanol produced modest, dose-related increases in the afferent activity from muscle spindles in spinal- and pentobarbital-anesthetized cats. Mean phasic and static discharge frequencies were both increased approximately 10 impulses/sec after infusions of a total of 2.8 g/kg. In unanesthetized animals, comparable blood levels of ethanol were associated with mild to marked motor incoordination. The mean amplitudes of the mono- and polysnaptic reflexes in spinal animals, elicited with supramaximal single shocks to the muscle nerve, were depressed to 92 and 84% of control levels, respectively, after 0.7 g/kg and continued to fall to 50 and 60% of control levels after 2.8 g/kg of ethanol. Ethanol failed to depress preferentially polysynaptic reflexes. It is concluded that the spindle afferent excitation was involved in the motor effects of ethanol but that it was insufficient to explain fully the skeletomotor alterations produced by ethanol; rather, ethanol actions at peripheral and spinal and, perhaps, supraspinal sites all appear to be involved in ethanol-induced impairment of motor function."} {"id": "PMID:1263127", "title": "Actions of trihexyphenidyl and benztropine on squid axon membranes.", "content": "Trihexyphenidyl and benztropine have potent local anesthetic action on squid axon membranes. They suppress the peak transient sodium conductance with ED50 values equal to 1.75 X 10(-4) AND 0.78 X 10(-4) M, respectively, and shift the sodium condu-tance curve along the potential axis in the direction of depolarization by 2.3 and 8.7 mV, respectively. The time for the sodium current to attain its peak is shortened. Steady-state potassium conductance is also suppressed by these drugs and undergoes an inactivation which has a potential-dependence characteristic. The local anesthetic action combined with the anticholinergic action may warrant further study of these two drugs, especially trihexyphenidyl, as a potential antiarrhythmic agent.", "contents": "Actions of trihexyphenidyl and benztropine on squid axon membranes. Trihexyphenidyl and benztropine have potent local anesthetic action on squid axon membranes. They suppress the peak transient sodium conductance with ED50 values equal to 1.75 X 10(-4) AND 0.78 X 10(-4) M, respectively, and shift the sodium condu-tance curve along the potential axis in the direction of depolarization by 2.3 and 8.7 mV, respectively. The time for the sodium current to attain its peak is shortened. Steady-state potassium conductance is also suppressed by these drugs and undergoes an inactivation which has a potential-dependence characteristic. The local anesthetic action combined with the anticholinergic action may warrant further study of these two drugs, especially trihexyphenidyl, as a potential antiarrhythmic agent."} {"id": "PMID:1263128", "title": "Methadone during pregnancy in the rat: dose level effects on maternal and perinatal mortality and growth in the offspring.", "content": "Four groups of pregnant rats were administered methadone hydrochloride orally on days 8 through 22 of gestation. Each group initially received 5 mg/kg for 4 days. One group was maintained at this level and the remaining groups were increased to maintenance doses of 10, 15 or 20 mg/kg increments at 4-day intervals. An intubation control group received the vehicle only. Nontreated control mothers were left undisturbed. All offspring were fostered to other nontreated mothers at birth. Methadone, particularly at the higher dose levels, reduced maternal weight gain during pregnancy and increased both maternal mortality and total mortality among the young (resorptions plus stillbirths). Birth weight covaried with dose level and litter size: the 5, 10 and 15 mg/kg doses yielded litter sizes comparable, to, or somewhat smaller than, controls, but with lower birth weights; the 20 mg/kg doses yielded the smallest litter sizes but with birth weights greater than any other treated or control group. Beyond day 1 of life, treated and control offspring did not differ in mortality. By weaning, the low offspring weights seen at birth had been compensated for and were no longer evident. Body weights of offspring of mothers in the 20 mg/kg group remained well above average through weaning. In a second experiment, blood levels of methadone were determined for both mothers and litters in the 5, 10 and 15 mg/kg groups, sacrificed 24 hours before expected parturition. Blood levels were dose-related and corresponded to those found in human subjects receiving daily maintenance doses of approximately 30, 60 and 100 mg, respectively.", "contents": "Methadone during pregnancy in the rat: dose level effects on maternal and perinatal mortality and growth in the offspring. Four groups of pregnant rats were administered methadone hydrochloride orally on days 8 through 22 of gestation. Each group initially received 5 mg/kg for 4 days. One group was maintained at this level and the remaining groups were increased to maintenance doses of 10, 15 or 20 mg/kg increments at 4-day intervals. An intubation control group received the vehicle only. Nontreated control mothers were left undisturbed. All offspring were fostered to other nontreated mothers at birth. Methadone, particularly at the higher dose levels, reduced maternal weight gain during pregnancy and increased both maternal mortality and total mortality among the young (resorptions plus stillbirths). Birth weight covaried with dose level and litter size: the 5, 10 and 15 mg/kg doses yielded litter sizes comparable, to, or somewhat smaller than, controls, but with lower birth weights; the 20 mg/kg doses yielded the smallest litter sizes but with birth weights greater than any other treated or control group. Beyond day 1 of life, treated and control offspring did not differ in mortality. By weaning, the low offspring weights seen at birth had been compensated for and were no longer evident. Body weights of offspring of mothers in the 20 mg/kg group remained well above average through weaning. In a second experiment, blood levels of methadone were determined for both mothers and litters in the 5, 10 and 15 mg/kg groups, sacrificed 24 hours before expected parturition. Blood levels were dose-related and corresponded to those found in human subjects receiving daily maintenance doses of approximately 30, 60 and 100 mg, respectively."} {"id": "PMID:1263129", "title": "Pharmacological studies of a new 4-aminosugar cardiac glycoside (ASI-222).", "content": "ASI-222,3beta-O-(4-amino-4,6-dideoxy-beta-d-galactopyranosyl) digitoxigenin, is a semi-synthetic cardiac glycoside patterned after a natural glycoside obtained from Cambodia. Effects of ASI-222 on contractile force in the isolated rabbit atria, cardiac contractile force, cardiac rate, ventricular excitability and functional refractory period in dogs, and acute toxicity in mice have been compared to those effects of ouabain. Both electrically driven and spontaneously beating atria demonstrated more rapid onset and greater maximum increases in contractile force with ASI-222 than with ouabain in equal bath concentrations. In the dog, ASI-222 increased cardiac contractile force more rapidly and at a lower cumulative dose than ouabain. Moreover, the maximum increase in contractile force obtained with ASI-222 was greater than that obtained with ouabain. The occurrence of ventricular ectopic beats was observed at a higher cumulative dose of ASI-222 than for ouabain. Also, ASI-222 produced a decrease in ventricular excitability and an increase in functional refractory period ot the ventricle. Ouabain, in the same molar dose, produced either no change or a slight increase in these parameters. Our data indicate that ASI-222 has a greater therapeutic index than ouabain. This difference may be partially explained by effects of ASI-222 on electrical properties of the heart.", "contents": "Pharmacological studies of a new 4-aminosugar cardiac glycoside (ASI-222). ASI-222,3beta-O-(4-amino-4,6-dideoxy-beta-d-galactopyranosyl) digitoxigenin, is a semi-synthetic cardiac glycoside patterned after a natural glycoside obtained from Cambodia. Effects of ASI-222 on contractile force in the isolated rabbit atria, cardiac contractile force, cardiac rate, ventricular excitability and functional refractory period in dogs, and acute toxicity in mice have been compared to those effects of ouabain. Both electrically driven and spontaneously beating atria demonstrated more rapid onset and greater maximum increases in contractile force with ASI-222 than with ouabain in equal bath concentrations. In the dog, ASI-222 increased cardiac contractile force more rapidly and at a lower cumulative dose than ouabain. Moreover, the maximum increase in contractile force obtained with ASI-222 was greater than that obtained with ouabain. The occurrence of ventricular ectopic beats was observed at a higher cumulative dose of ASI-222 than for ouabain. Also, ASI-222 produced a decrease in ventricular excitability and an increase in functional refractory period ot the ventricle. Ouabain, in the same molar dose, produced either no change or a slight increase in these parameters. Our data indicate that ASI-222 has a greater therapeutic index than ouabain. This difference may be partially explained by effects of ASI-222 on electrical properties of the heart."} {"id": "PMID:1263130", "title": "Impaired tissue oxygenation in cyanate-treated animals.", "content": "Carbamylation of red cells with sodium cyanate has been suggested as a potential treatment for sickle cell disease. Because carbamylation of red cells increases their oxygen affinity, the present study was done to determine whether cyanate administration caused impaired tissue oxygenation. Rats given i.p. (250 mg/kg/wk) or oral (625 mg/kg/wk) cyanate were found to have significantly reduced skin bubble oxygen tensions compared to controls. These reduced oxygen tensions were associated with significantly increased blood oxygen affinity. Treated animals developed greater red cell masses than controls, but these increases were not sufficient to compensate for increased blood oxygen affinity. These findings need to be considered when cyanate is used for treatment of sickle cell disease.", "contents": "Impaired tissue oxygenation in cyanate-treated animals. Carbamylation of red cells with sodium cyanate has been suggested as a potential treatment for sickle cell disease. Because carbamylation of red cells increases their oxygen affinity, the present study was done to determine whether cyanate administration caused impaired tissue oxygenation. Rats given i.p. (250 mg/kg/wk) or oral (625 mg/kg/wk) cyanate were found to have significantly reduced skin bubble oxygen tensions compared to controls. These reduced oxygen tensions were associated with significantly increased blood oxygen affinity. Treated animals developed greater red cell masses than controls, but these increases were not sufficient to compensate for increased blood oxygen affinity. These findings need to be considered when cyanate is used for treatment of sickle cell disease."} {"id": "PMID:1263131", "title": "Correlation of the electrophysiological and antiarrhythmic properties of the N-acetyl metabolite of procainamide with plasma and tissue drug concentrations in the dog.", "content": "N-acetylprocainamide (NAPA), a major metabolite of procainamide (PA) in man, has been reported recently to be biologically active. The present study compares the electrophysiological and antiarrhythmic effects of NAPA and PA and correlates their activity with plasma and tissue drug concentrations. In isolated canine Purkinje fibers, NAPA, in bath concentrations of 10 and 20 mg/l reduced automaticity and prolonged repolarization time. These effects were similar to those observed with similar concentrations of PA. Tissue concentrations of NAPA (77 +/- 2 mug/g) were significantly greater than those of PA (43+/-2 mug/g). Neither drug was metabolized by the fibers. In in vivo studies, NAPA (140-220 mg/kg) significantly suppressed the incidence of arrhythmias following coronary occlusion and digitalis intoxication. Similar protection was obtained with 40 to 60 mg/kg of PA. This difference in potency could not be attributed to differences in plasma and tissue concentrations of the drugs. These results show that NAPA is equally efficacious but less potent than PA as an antiarrhythmic drug in dogs.", "contents": "Correlation of the electrophysiological and antiarrhythmic properties of the N-acetyl metabolite of procainamide with plasma and tissue drug concentrations in the dog. N-acetylprocainamide (NAPA), a major metabolite of procainamide (PA) in man, has been reported recently to be biologically active. The present study compares the electrophysiological and antiarrhythmic effects of NAPA and PA and correlates their activity with plasma and tissue drug concentrations. In isolated canine Purkinje fibers, NAPA, in bath concentrations of 10 and 20 mg/l reduced automaticity and prolonged repolarization time. These effects were similar to those observed with similar concentrations of PA. Tissue concentrations of NAPA (77 +/- 2 mug/g) were significantly greater than those of PA (43+/-2 mug/g). Neither drug was metabolized by the fibers. In in vivo studies, NAPA (140-220 mg/kg) significantly suppressed the incidence of arrhythmias following coronary occlusion and digitalis intoxication. Similar protection was obtained with 40 to 60 mg/kg of PA. This difference in potency could not be attributed to differences in plasma and tissue concentrations of the drugs. These results show that NAPA is equally efficacious but less potent than PA as an antiarrhythmic drug in dogs."} {"id": "PMID:1263132", "title": "Vascular tone and reactivity to serotonin in the internal and external carotid vascular beds of the dog.", "content": "The effects of intra-arterial infusions of serotonin on internal and external carotid blood flow were determined in anesthetized dogs by electromagnetic flow measurements. Serotonin decreased flow in the internal carotid and increased it in the external carotid. Both responses were blocked by the serotonin antagonist methysergide. The alpha adrenergic antagonist zolertine, the ganglionic blocking agent chlorisondamine and the vasodilator diazoxide blocked external carotid dilator responses but did not modify constriction in the internal carotid. Blockade of external carotid responses by the three drugs was also demonstrated in experiments in which this bed was perfused at a constant rate. These results indicate that the internal and external carotid vascular beds of the dog react in opposite ways to serotonin, that both responses are mediated through the same type of serotonin receptors and that the dilator responses of the external carotid are dependent on vascular tone.", "contents": "Vascular tone and reactivity to serotonin in the internal and external carotid vascular beds of the dog. The effects of intra-arterial infusions of serotonin on internal and external carotid blood flow were determined in anesthetized dogs by electromagnetic flow measurements. Serotonin decreased flow in the internal carotid and increased it in the external carotid. Both responses were blocked by the serotonin antagonist methysergide. The alpha adrenergic antagonist zolertine, the ganglionic blocking agent chlorisondamine and the vasodilator diazoxide blocked external carotid dilator responses but did not modify constriction in the internal carotid. Blockade of external carotid responses by the three drugs was also demonstrated in experiments in which this bed was perfused at a constant rate. These results indicate that the internal and external carotid vascular beds of the dog react in opposite ways to serotonin, that both responses are mediated through the same type of serotonin receptors and that the dilator responses of the external carotid are dependent on vascular tone."} {"id": "PMID:1263133", "title": "The influence of mecamylamine on contractions induced by different agonists and on the role of calcium ions in the isolated rabbit aorta.", "content": "The exposure of helically cut strips of rabbit aorta to mecamylamine (1 mM) for 5 minutes blocked the histamine (3.25 muM)-induced contractions completely and reduced those induced by potassium (25mM, 68%) without affecting contractions induced by norepinephrine (3.0 muM, NE) or acetylcholine (10 muM). Mecamylamine, by itself, did not exhibit agonist activity, but it increased the contractile tension of the muscle which was contracted by NE. The responses to NE were either enhanced or not affected by small doses of mecamylamine (1 mM), but were partially blocked by large doses of mecamylamine (10 mM). The antagonism exhibited by mecamylamine in low doses (1 mM) against the above agonists was reversible. The shape of the response to NE on the muscle, which was treated with a high dose of mecamylamine (20 mM) and washed, was significantly different from that of the control. Our results are consistent with the following conclusions: 1) Mecamylamine in low doses (1 mM) blocks the histamine receptor and therefore the histamine-induced contractions. Two molecules of mecamylamine are competitive with 1 molecule of histamine. 2) Mecamylamine blocks the potassium-induced contractions, but does not block completely the calcium influx in the potassium-depolarized muscles. Therefore, it may interfere partially with the utilization of extracellular or loosely bound calcium during potassium-induced contractions. 3) Mecamylamine in high doses (10 mM) partially blocks norepinephrine-induced contractions by affecting firmly bound calcium stores. 4) Procaine antagonizes the effects of NE, histamine and acetylcholine by affecting, at least partially, the firmly bound calcium stores.", "contents": "The influence of mecamylamine on contractions induced by different agonists and on the role of calcium ions in the isolated rabbit aorta. The exposure of helically cut strips of rabbit aorta to mecamylamine (1 mM) for 5 minutes blocked the histamine (3.25 muM)-induced contractions completely and reduced those induced by potassium (25mM, 68%) without affecting contractions induced by norepinephrine (3.0 muM, NE) or acetylcholine (10 muM). Mecamylamine, by itself, did not exhibit agonist activity, but it increased the contractile tension of the muscle which was contracted by NE. The responses to NE were either enhanced or not affected by small doses of mecamylamine (1 mM), but were partially blocked by large doses of mecamylamine (10 mM). The antagonism exhibited by mecamylamine in low doses (1 mM) against the above agonists was reversible. The shape of the response to NE on the muscle, which was treated with a high dose of mecamylamine (20 mM) and washed, was significantly different from that of the control. Our results are consistent with the following conclusions: 1) Mecamylamine in low doses (1 mM) blocks the histamine receptor and therefore the histamine-induced contractions. Two molecules of mecamylamine are competitive with 1 molecule of histamine. 2) Mecamylamine blocks the potassium-induced contractions, but does not block completely the calcium influx in the potassium-depolarized muscles. Therefore, it may interfere partially with the utilization of extracellular or loosely bound calcium during potassium-induced contractions. 3) Mecamylamine in high doses (10 mM) partially blocks norepinephrine-induced contractions by affecting firmly bound calcium stores. 4) Procaine antagonizes the effects of NE, histamine and acetylcholine by affecting, at least partially, the firmly bound calcium stores."} {"id": "PMID:1263134", "title": "Iris pigmentation and atropine mydriasis.", "content": "The experiments were designed to study the well-known pigment-dependent mydriatic effect of atropine in the eye. In vitro, relative to the accumulation of 3H-atropine by the nonpigmented rabbit iris, the pigmented iris accumulated high amounts of the drug. A nonpigmented tissue, stomch fundus strip, obtained from either albino or nonalbino animals, accumulated relatively low amounts of 3H-atropine. On repeated washings, the accumulated drug from the nonpigmented tissues was rapidly lost, T 1/2 of 14 minutes, while that accumulated by the pigmented iris was retained much longer. Although in vitro aqueous humor from serum-atropinesterase positive rabbits rapidly degraded atropine, extracts from irides of the same type of rabbit gave a single peak radioactivity, with Rf identical to the authentic atropine sulfate. The accumulation of 3H-atropine by pigmented human iris or pigment epithelium was similar to that observed for the pigmented rabbit iris. pA2 values of atropine from nonpigmented iris and from fundus strips varied between 8.58 and 8.88 with slope values close to 1. The pA2 value of atropine in pigmented iris was 8.82; at higher concentrations, atropine was less effective compared to the nonpigmented iris. In the pigmented iris, the lesser effectiveness of the drug at high concentration could be explained on the basis of accumulation of the drug by the pigment cell and its constituents. Thus, the free concentration of the drug in the vicinity of the muscarinic receptor will fall. The lesser concentration will give weaker muscarinic blockade in the pigmented iris. On repeated washing, the atropine blockade of the nonpigmented iris could be easily washed out while that in the pigmented iris was retained. In vivo, the relative T 1/2 for the duration of atropine mydriasis in rabbits were: albino atropinesterase-positive, 3.8 hours; nonalbino atropinesterase-positive, 12.4 hours; albino atropinesterase-negative is greater than or equal to 96 hours. Only the latter T 1/2 for the duration of atropine mydriasis is quite clear. The small magnitude of the mydriatic effect in humans is explained by the loss of free drug to the pigment cells and their constituents. The longer duration of mydriatic effect in the heavily pigmented eye is explained on the basis of slow release of the accumulated drug onto the muscarinic receptor.", "contents": "Iris pigmentation and atropine mydriasis. The experiments were designed to study the well-known pigment-dependent mydriatic effect of atropine in the eye. In vitro, relative to the accumulation of 3H-atropine by the nonpigmented rabbit iris, the pigmented iris accumulated high amounts of the drug. A nonpigmented tissue, stomch fundus strip, obtained from either albino or nonalbino animals, accumulated relatively low amounts of 3H-atropine. On repeated washings, the accumulated drug from the nonpigmented tissues was rapidly lost, T 1/2 of 14 minutes, while that accumulated by the pigmented iris was retained much longer. Although in vitro aqueous humor from serum-atropinesterase positive rabbits rapidly degraded atropine, extracts from irides of the same type of rabbit gave a single peak radioactivity, with Rf identical to the authentic atropine sulfate. The accumulation of 3H-atropine by pigmented human iris or pigment epithelium was similar to that observed for the pigmented rabbit iris. pA2 values of atropine from nonpigmented iris and from fundus strips varied between 8.58 and 8.88 with slope values close to 1. The pA2 value of atropine in pigmented iris was 8.82; at higher concentrations, atropine was less effective compared to the nonpigmented iris. In the pigmented iris, the lesser effectiveness of the drug at high concentration could be explained on the basis of accumulation of the drug by the pigment cell and its constituents. Thus, the free concentration of the drug in the vicinity of the muscarinic receptor will fall. The lesser concentration will give weaker muscarinic blockade in the pigmented iris. On repeated washing, the atropine blockade of the nonpigmented iris could be easily washed out while that in the pigmented iris was retained. In vivo, the relative T 1/2 for the duration of atropine mydriasis in rabbits were: albino atropinesterase-positive, 3.8 hours; nonalbino atropinesterase-positive, 12.4 hours; albino atropinesterase-negative is greater than or equal to 96 hours. Only the latter T 1/2 for the duration of atropine mydriasis is quite clear. The small magnitude of the mydriatic effect in humans is explained by the loss of free drug to the pigment cells and their constituents. The longer duration of mydriatic effect in the heavily pigmented eye is explained on the basis of slow release of the accumulated drug onto the muscarinic receptor."} {"id": "PMID:1263135", "title": "Dopamine synthesis in rat brain striatal synaptosomes. I. Correlations between veratridine-induced synthesis stimulation and endogenous dopamine release.", "content": "The effects of depolarizing concentrations of veratridine were studied to determine the degree to which dopamine synthesis stimulation was correlated with stimulated endogenous dopamine release in rat brain striatal synaptosomes. Incubations included cocaine and pargyline to prevent dopamine reuptake and metabolism, respectively. Veratridine produced a 44% increase in dopamine release in 10 minutes and a similar increase in synthesis rate. Preincubation with tetrodotoxin prevented the increase in both release and synthesis, while incubation in a calcium-free medium antagonized both responses approximately 50%. Addition of 1 mM ethylene glycol bis(beta-aminoethylether)-N, N'-tetraacetic acid to the calcium-free incubation medium further inhibited the release response, but not the synthesis stimulation. These results indicate that, in general, the degree of synthesis stimulation produced by depolarizing agents such as veratridine can be correlated with their stimulation of dopamine release, suggesting either 1)that transmitter release itself is a signal for synthesis stimulation, possibly by removal of feedback inhibition of tyrosine hydroxylase or 2) that depolarizing agents increase synthesis through a secondary metabolic change that is either caused by, or at least accompanied by, transmitter release.", "contents": "Dopamine synthesis in rat brain striatal synaptosomes. I. Correlations between veratridine-induced synthesis stimulation and endogenous dopamine release. The effects of depolarizing concentrations of veratridine were studied to determine the degree to which dopamine synthesis stimulation was correlated with stimulated endogenous dopamine release in rat brain striatal synaptosomes. Incubations included cocaine and pargyline to prevent dopamine reuptake and metabolism, respectively. Veratridine produced a 44% increase in dopamine release in 10 minutes and a similar increase in synthesis rate. Preincubation with tetrodotoxin prevented the increase in both release and synthesis, while incubation in a calcium-free medium antagonized both responses approximately 50%. Addition of 1 mM ethylene glycol bis(beta-aminoethylether)-N, N'-tetraacetic acid to the calcium-free incubation medium further inhibited the release response, but not the synthesis stimulation. These results indicate that, in general, the degree of synthesis stimulation produced by depolarizing agents such as veratridine can be correlated with their stimulation of dopamine release, suggesting either 1)that transmitter release itself is a signal for synthesis stimulation, possibly by removal of feedback inhibition of tyrosine hydroxylase or 2) that depolarizing agents increase synthesis through a secondary metabolic change that is either caused by, or at least accompanied by, transmitter release."} {"id": "PMID:1263137", "title": "The effect of external calcium and magnesium ions on the response of denervated muscle to acetylcholine.", "content": "1. The effect of external Ca and Mg on the membrane depolarization and contracture of rat denervated muscle in response to acetylcholine, ACh, was studied. 2. Raising external Ca concentration reduced the rate of rise and the amplitude of the ACh contracture, and prolonged its time course. 3. Increasing external Ca reduced the membrane depolarization in response to ACh. The dose increment required to elicit depolarization in high Ca concentration increased with external Ca, and was greater for depolarization than for contracture. 4. External Mg was less effect than Ca in reducing ACh depolarization but was more effective in reducing contracture. In contrast to Ca, Mg did not alter the time course of relaxation. 5. It is concluded that external Ca has two opposing effects on the ACh contracture: one of stabilizing the membrane and the other of increasing intracellular Ca concentration. External Mg may interfere with Ca influx and hence reduce contractility.", "contents": "The effect of external calcium and magnesium ions on the response of denervated muscle to acetylcholine. 1. The effect of external Ca and Mg on the membrane depolarization and contracture of rat denervated muscle in response to acetylcholine, ACh, was studied. 2. Raising external Ca concentration reduced the rate of rise and the amplitude of the ACh contracture, and prolonged its time course. 3. Increasing external Ca reduced the membrane depolarization in response to ACh. The dose increment required to elicit depolarization in high Ca concentration increased with external Ca, and was greater for depolarization than for contracture. 4. External Mg was less effect than Ca in reducing ACh depolarization but was more effective in reducing contracture. In contrast to Ca, Mg did not alter the time course of relaxation. 5. It is concluded that external Ca has two opposing effects on the ACh contracture: one of stabilizing the membrane and the other of increasing intracellular Ca concentration. External Mg may interfere with Ca influx and hence reduce contractility."} {"id": "PMID:1263138", "title": "Quantitative assessment of the transmission of labelled protein by the proximal and distal regions of the small intestine of young rats.", "content": "1. The plasma volume in rats aged 15-16 days was measured by dilution analysis using homologous, 125I-labelled immunoglobulin G. A mean plasma volume of 5-53 ml./100 g and a mean blood volume of 8-01 ml./100 g were obtained.2. After the injection of labelled immunoglobulin G into the heart, homogenates of various abdominal organs and of the carcass were prepared. Labelled immunoglobulin G left the vascular compartment at a rate of about 9-10%/hr over a 3 hr period. About 11% of the labelled immunoglobulin G was catabolized in 2 hr. 3. The data obtained from these studies was used to make quantitative estimates of the amount of intact immunoglobulin G transmitted from the proximal intestine and from the ileum after the intra-intestinal injection of 1000 mug of labelled immunoglobulin G. Homogenates of the experimental animals were prepared and it was estimated that over 40% of the labelled immunoglobulin G was transmitted as intact protein from the proximal intestine. The results suggest that no intact immunoglobulin G was transmitted from the ileum, but about 15% of the protein removed from the ileum was recovered in the whole body as degraded fragments precipitable with trichloroacetic acid. 4. These observations are discussed in the context of the transmission of antibodies, and their relevance to the receptor hypothesis is considered.", "contents": "Quantitative assessment of the transmission of labelled protein by the proximal and distal regions of the small intestine of young rats. 1. The plasma volume in rats aged 15-16 days was measured by dilution analysis using homologous, 125I-labelled immunoglobulin G. A mean plasma volume of 5-53 ml./100 g and a mean blood volume of 8-01 ml./100 g were obtained.2. After the injection of labelled immunoglobulin G into the heart, homogenates of various abdominal organs and of the carcass were prepared. Labelled immunoglobulin G left the vascular compartment at a rate of about 9-10%/hr over a 3 hr period. About 11% of the labelled immunoglobulin G was catabolized in 2 hr. 3. The data obtained from these studies was used to make quantitative estimates of the amount of intact immunoglobulin G transmitted from the proximal intestine and from the ileum after the intra-intestinal injection of 1000 mug of labelled immunoglobulin G. Homogenates of the experimental animals were prepared and it was estimated that over 40% of the labelled immunoglobulin G was transmitted as intact protein from the proximal intestine. The results suggest that no intact immunoglobulin G was transmitted from the ileum, but about 15% of the protein removed from the ileum was recovered in the whole body as degraded fragments precipitable with trichloroacetic acid. 4. These observations are discussed in the context of the transmission of antibodies, and their relevance to the receptor hypothesis is considered."} {"id": "PMID:1263139", "title": "Permeability changes produced by L-glutamate at the excitatory post-synaptic membrane of the crayfish muscle.", "content": "1. Permeability changes produced by L-glutamate at the neuromuscular junction of the crayfish (Cambarus clarkii) were investigated by application of the drug iontophoretically to the voltage-clamped junction and measuring the resulting 'glutamate current'. 2. Reversal potentials were determined by measuring the glutamate current at different membrane potentials. They were +39-1 +/- 3-6 mV (mean +/- S.E. of mean) in normal solution and +16-5 +/- 2-0 mV in solutions made twice as hypertonic by the addition of sucrose. 3. Decreasing external Na+ concentration shifted the reversal potential in the negative direction; increased Na+ in the positive direction. 4. The relation between the amplitude of the glutamate current and extracellular Na+ concentration was approximately linear. 5. Alteration of the external K+ or Cl- concentration did not affect the amplitude or reversal potential of glutamate current. 6. In Na+-free solution the application of L-glutamate produced a small inward current at the resting potential and its amplitude was augmented by increasing the external Ca2+ concentration. 7. Increasing the Ca2+ concentration in the normal Na+ media produced no appreciable effect on the reversal potential but decreased the amplitude of glutamate current. 8. The results indicate that L-glutamate increases the membrane permeability mainly to Na+ and slightly to Ca2+. 9. The time course of glutamate current was shorter than that of the concentration calculated from the diffusion equation and it was simulated more closely by the square of the concentration.", "contents": "Permeability changes produced by L-glutamate at the excitatory post-synaptic membrane of the crayfish muscle. 1. Permeability changes produced by L-glutamate at the neuromuscular junction of the crayfish (Cambarus clarkii) were investigated by application of the drug iontophoretically to the voltage-clamped junction and measuring the resulting 'glutamate current'. 2. Reversal potentials were determined by measuring the glutamate current at different membrane potentials. They were +39-1 +/- 3-6 mV (mean +/- S.E. of mean) in normal solution and +16-5 +/- 2-0 mV in solutions made twice as hypertonic by the addition of sucrose. 3. Decreasing external Na+ concentration shifted the reversal potential in the negative direction; increased Na+ in the positive direction. 4. The relation between the amplitude of the glutamate current and extracellular Na+ concentration was approximately linear. 5. Alteration of the external K+ or Cl- concentration did not affect the amplitude or reversal potential of glutamate current. 6. In Na+-free solution the application of L-glutamate produced a small inward current at the resting potential and its amplitude was augmented by increasing the external Ca2+ concentration. 7. Increasing the Ca2+ concentration in the normal Na+ media produced no appreciable effect on the reversal potential but decreased the amplitude of glutamate current. 8. The results indicate that L-glutamate increases the membrane permeability mainly to Na+ and slightly to Ca2+. 9. The time course of glutamate current was shorter than that of the concentration calculated from the diffusion equation and it was simulated more closely by the square of the concentration."} {"id": "PMID:1263140", "title": "Haemodynamic responses and renin release during stimulation of afferent renal nerves in the cat.", "content": "1. Experiments were done on anaesthetized cats to study the effect of electrical stimulation of afferent renal nerves on the circulatory system and on the release of renin from the kidney. 2. Stimulation of afferent renal nerves over a wide range of parameters consistently elicited an increase in arterial pressure and heart rate. This response was still present in paralysed animals and was not accompanied by changes in respiration or in sympathetic autonomic activity usually associated with painful stimulation. Mesenteric and iliac vasoconstriction was observed concomitantly with the increase in arterial pressure. 3. Release of renin from the contralateral innervated kidney was not significantly changed by stimulation of afferent renal nerves. 4. The existence of renal vascular mechanoreceptors was investigated by altering renal circulation. Stenosis of the renal artery or a marked reduction in renal perfusion pressure elicited an increase in arterial pressure while stenosis of the renal vein elicited a decrease in arterial pressure. These responses, however, were not affected by denervation of the kidney and were therefore interpreted as not being due to neural mechanisms. 5. The precise nature, location and physiological role of renal receptors involved in the cardiovascular responses observed during electrical stimulation of afferent renal nerves remain to be determined.", "contents": "Haemodynamic responses and renin release during stimulation of afferent renal nerves in the cat. 1. Experiments were done on anaesthetized cats to study the effect of electrical stimulation of afferent renal nerves on the circulatory system and on the release of renin from the kidney. 2. Stimulation of afferent renal nerves over a wide range of parameters consistently elicited an increase in arterial pressure and heart rate. This response was still present in paralysed animals and was not accompanied by changes in respiration or in sympathetic autonomic activity usually associated with painful stimulation. Mesenteric and iliac vasoconstriction was observed concomitantly with the increase in arterial pressure. 3. Release of renin from the contralateral innervated kidney was not significantly changed by stimulation of afferent renal nerves. 4. The existence of renal vascular mechanoreceptors was investigated by altering renal circulation. Stenosis of the renal artery or a marked reduction in renal perfusion pressure elicited an increase in arterial pressure while stenosis of the renal vein elicited a decrease in arterial pressure. These responses, however, were not affected by denervation of the kidney and were therefore interpreted as not being due to neural mechanisms. 5. The precise nature, location and physiological role of renal receptors involved in the cardiovascular responses observed during electrical stimulation of afferent renal nerves remain to be determined."} {"id": "PMID:1263141", "title": "The effect of hypercapnia on a blood-brain barrier mechanism in foetal and new-born sheep.", "content": "1. The effect of marked hypercapnia (arterial PCO2 100 mmHg), nonrespiratory acidosis (pH 6-95-7-15) or hypoxia (arterial PO2 10-15 mmHg) upon penetration of labelled sucrose from blood into brain and c.s.f. has been investigated in exteriorized foetal sheep and new-born lambs. 2. In hypercapnia there was a consistent increase in c.s.f./plasma sucrose ratio after 90 min I.V. sucrose to four to five times control. Brain/plasma sucrose ratios were more variable. Usually there was an increase (up to three-and-a-half-times control); sometimes there was no change or even a decrease. The effect of hypercapnia on sucrose penetration was reversible. 3. Hypercapnia reduced c.s.f. secretion rate to approximately half the control value. Hypercapnia also caused a decrease in brain extracellular space. 4. Non-respiratory acidosis did not affect sucrose penetration. Hypoxia caused a decrease in brain/plasma sucrose ratio. 5. It is concluded that hypercapnia can cuase an increase in cerebral vascular permeability to sucrose in foetal and new-born sheep. Some possible mechanisms are discussed.", "contents": "The effect of hypercapnia on a blood-brain barrier mechanism in foetal and new-born sheep. 1. The effect of marked hypercapnia (arterial PCO2 100 mmHg), nonrespiratory acidosis (pH 6-95-7-15) or hypoxia (arterial PO2 10-15 mmHg) upon penetration of labelled sucrose from blood into brain and c.s.f. has been investigated in exteriorized foetal sheep and new-born lambs. 2. In hypercapnia there was a consistent increase in c.s.f./plasma sucrose ratio after 90 min I.V. sucrose to four to five times control. Brain/plasma sucrose ratios were more variable. Usually there was an increase (up to three-and-a-half-times control); sometimes there was no change or even a decrease. The effect of hypercapnia on sucrose penetration was reversible. 3. Hypercapnia reduced c.s.f. secretion rate to approximately half the control value. Hypercapnia also caused a decrease in brain extracellular space. 4. Non-respiratory acidosis did not affect sucrose penetration. Hypoxia caused a decrease in brain/plasma sucrose ratio. 5. It is concluded that hypercapnia can cuase an increase in cerebral vascular permeability to sucrose in foetal and new-born sheep. Some possible mechanisms are discussed."} {"id": "PMID:1263142", "title": "The utilization of glucose and production of lactate by in vitro preparations of rat small intestine: effects of vascular perfusion.", "content": "1. The rate of metabolism of glucose to lactate has been measured in a number of non-vascularly perfused preparations of rat jejunum in vitro. The glucose and lactate metabolism was measured simultaneously and under conditions such that the uptake of glucose and the appearance of lactate were linearly related to time. 2. It is found that there is no difference between the rates at which rings of rat jejunum utilize glucose during the first 45 min of anaerobic or aerobic incubation. During the first 15 min of incubation between 60-70% of the metabolized glucose was converted to lactate under aerobic conditions; this value increased to 80-90% during the subsequent 30 min. During the period 0-15 min of incubation, lactate production was found to be higher under anaerobic than under aerobic conditions but after this initial period the rate of lactate production was the same under aerobic and anaerobic conditions. 3. For segments of rat jejunum, maintained in vitro by the recirculation of nutrient fluid through the intestinal lumen, neither the rate of production of lactate, nor the utilization of glucose, was stimulated if the preparation was maintained under anaerobic rather than aerobic conditions. The direct delivery of gas into the intestinal lumen in the form of a stream of bubbles (segmented circulation) reduced both the utilization of glucose and the production of lactate under aerobic conditions. However, not effect on glucose metabolism was observed under anaerobic conditions. The finding of a Pasteur effect with the segmented-circulated preparation, but not with the simple recirculated preparation, is associated with lower rate of aerobic lactate production in the former preparation. Reasons are given for supposing that under conditions of segmented circulation, the luminal compartment is better stirred, thereby increasing access of O2 to the tissue. 4. A preparation of rat small intestine perfused through the vascular bed is described. With this preparation the rate of glucose utilization is significantly lower than that for recirculated preparations and the rate of lactate production is substantially less than that of the other preparations studied. 5. With the preparation perfused through the vascular bed, and with glucose, 10 mM, present only in the vascular medium the addition of erythrocytes to the vascular infusate causes a significant reduction in both glucose utilization and in the rate of lactate production. The addition of erythrocytes to produce an haematocrit of 40% (v/v) causes a greater reduction in glucose utilization and lactate production than is found for an haematrocrit of 15%. About 10% of the lactate produced appears in the luminal contents. With an haematocrit of 15%, the O2 consumption of the whole wall of the jejunum was found to be 6-4 mumole O2 g dry wt.-1 min-1, equivalent of a value for the Q02 of 8-6 mul. O2 mg druwy wt.-1 hr-1. The uptake of O2 was almost entirely from the vascular infusate. 6...", "contents": "The utilization of glucose and production of lactate by in vitro preparations of rat small intestine: effects of vascular perfusion. 1. The rate of metabolism of glucose to lactate has been measured in a number of non-vascularly perfused preparations of rat jejunum in vitro. The glucose and lactate metabolism was measured simultaneously and under conditions such that the uptake of glucose and the appearance of lactate were linearly related to time. 2. It is found that there is no difference between the rates at which rings of rat jejunum utilize glucose during the first 45 min of anaerobic or aerobic incubation. During the first 15 min of incubation between 60-70% of the metabolized glucose was converted to lactate under aerobic conditions; this value increased to 80-90% during the subsequent 30 min. During the period 0-15 min of incubation, lactate production was found to be higher under anaerobic than under aerobic conditions but after this initial period the rate of lactate production was the same under aerobic and anaerobic conditions. 3. For segments of rat jejunum, maintained in vitro by the recirculation of nutrient fluid through the intestinal lumen, neither the rate of production of lactate, nor the utilization of glucose, was stimulated if the preparation was maintained under anaerobic rather than aerobic conditions. The direct delivery of gas into the intestinal lumen in the form of a stream of bubbles (segmented circulation) reduced both the utilization of glucose and the production of lactate under aerobic conditions. However, not effect on glucose metabolism was observed under anaerobic conditions. The finding of a Pasteur effect with the segmented-circulated preparation, but not with the simple recirculated preparation, is associated with lower rate of aerobic lactate production in the former preparation. Reasons are given for supposing that under conditions of segmented circulation, the luminal compartment is better stirred, thereby increasing access of O2 to the tissue. 4. A preparation of rat small intestine perfused through the vascular bed is described. With this preparation the rate of glucose utilization is significantly lower than that for recirculated preparations and the rate of lactate production is substantially less than that of the other preparations studied. 5. With the preparation perfused through the vascular bed, and with glucose, 10 mM, present only in the vascular medium the addition of erythrocytes to the vascular infusate causes a significant reduction in both glucose utilization and in the rate of lactate production. The addition of erythrocytes to produce an haematocrit of 40% (v/v) causes a greater reduction in glucose utilization and lactate production than is found for an haematrocrit of 15%. About 10% of the lactate produced appears in the luminal contents. With an haematocrit of 15%, the O2 consumption of the whole wall of the jejunum was found to be 6-4 mumole O2 g dry wt.-1 min-1, equivalent of a value for the Q02 of 8-6 mul. O2 mg druwy wt.-1 hr-1. The uptake of O2 was almost entirely from the vascular infusate. 6..."} {"id": "PMID:1263143", "title": "[Influence of hydrothermal ambient conditions on sweat evaporation efficiency].", "content": "Sweat efficiency is defined as the ratio between evaporative and sweat rates. The work was carried out on two resting subjects acclimatised to humid heat. Body sweat rate and rate of sweat loss by dripping were recorded separately by continuous weighing. Evaporation from the skin was obtained by the difference between the two weight loss curves. The subjects were exposed for 75 minutes to increases in humidity levels as constant air temperatures (42, 44, 46, or 48 degrees C). The amplitude of the increases was successively equal to 7.5, 15.0, 22.5 or 50.0 mb of water vapor pressure. During the 75 minutes preceding each increase the water vapor pressure of the air was maintained at 20.0 mb. 1. Sweat efficiency decreases prior to complete wetting of the skin surface. The inter-individual mean value of the wetted skin area threshold over which sweat efficiency is less than 1 is around 60%. 2. Sweat efficiency is linearly related to the reciprocal of the required wetted skin area (see article). These results are compared with those of other authors. The differences observed are explained in terms of physiological or physical variables involved in the sweat rate control or in the evaporative sweat loss. These include wetness of skin, posture, activity of subjects and the velocity of air over the skin surface.", "contents": "[Influence of hydrothermal ambient conditions on sweat evaporation efficiency]. Sweat efficiency is defined as the ratio between evaporative and sweat rates. The work was carried out on two resting subjects acclimatised to humid heat. Body sweat rate and rate of sweat loss by dripping were recorded separately by continuous weighing. Evaporation from the skin was obtained by the difference between the two weight loss curves. The subjects were exposed for 75 minutes to increases in humidity levels as constant air temperatures (42, 44, 46, or 48 degrees C). The amplitude of the increases was successively equal to 7.5, 15.0, 22.5 or 50.0 mb of water vapor pressure. During the 75 minutes preceding each increase the water vapor pressure of the air was maintained at 20.0 mb. 1. Sweat efficiency decreases prior to complete wetting of the skin surface. The inter-individual mean value of the wetted skin area threshold over which sweat efficiency is less than 1 is around 60%. 2. Sweat efficiency is linearly related to the reciprocal of the required wetted skin area (see article). These results are compared with those of other authors. The differences observed are explained in terms of physiological or physical variables involved in the sweat rate control or in the evaporative sweat loss. These include wetness of skin, posture, activity of subjects and the velocity of air over the skin surface."} {"id": "PMID:1263144", "title": "Effect of environmental salinity change on osmotic permeability of the isolated gill of the eel, Anguilla anguilla L.", "content": "Net water fluxes in the isolated gills of Anguilla anguilla were studied during incubation in fresh water (FW) and in sea water (SW). When incubated in FW, water entry was greater in SW-adapted eels than in FW-adapted eels. In contrast, water loss in SW was less in SW-adapted eels than in FW-adapted eels. Rectification of osmotic water fluxes was observed for both FW and SW-adapted eels, net water fluxes in the mucosal-serosal (m-s) direction being greater than those in the opposite (s-m) direction. These results indicate that adaptation to a given external medium brings about a decrease in the osmotic permeability so that water gain in FW or water loss in SW is minimal.", "contents": "Effect of environmental salinity change on osmotic permeability of the isolated gill of the eel, Anguilla anguilla L. Net water fluxes in the isolated gills of Anguilla anguilla were studied during incubation in fresh water (FW) and in sea water (SW). When incubated in FW, water entry was greater in SW-adapted eels than in FW-adapted eels. In contrast, water loss in SW was less in SW-adapted eels than in FW-adapted eels. Rectification of osmotic water fluxes was observed for both FW and SW-adapted eels, net water fluxes in the mucosal-serosal (m-s) direction being greater than those in the opposite (s-m) direction. These results indicate that adaptation to a given external medium brings about a decrease in the osmotic permeability so that water gain in FW or water loss in SW is minimal."} {"id": "PMID:1263145", "title": "[Function of different medullary neurons in respiration].", "content": "1. We have studied the activity of 162 medullary respiratory neurones in the \"encephale isole bas\" cat. These neurones were classed into three groups : bulbospinal inspiratory (NBSI : 39) or expiratory (NBSE : 15) neurones whose axons enter the spinal cord ; inspiratory or expiratory laryngeal motoneurones (MLI : 17; MLE : 10) antidromically activated by vagus nerve stimulation ; propriobulbar inspiratory (NPBI : 59) or expiratory (NPBE : 22) neurones whose axons lie perhaps entirely within the medulla. 2. Correlation coefficients between number of spikes delivered in each burst and the duration of the corresponding respiratory phase (inspiration for NBSI, MLI, NPBI ; expiration for NBSE, MLE, NPBE) have been calculated for each neurone. 3. The activity of most of the NBSI and MLI is significantly correlated with the duration of the inspiration. These two groups of neurones are probably homogenous. 4. On the basis of this correlation test, NPBI do not constitute an homogeneous population ; 50% of NPBI are not significantly correlated. The same results are obtained if correlations are calculated between the number of spikes delivered and the amplitude of integrated phrenic nerve acitivty. According to the discharge pattern and correlation test, we can consider three groups of NPBI : early recruited neurones with decreasing frequency and non significantly correlated activity (23,7%); early and late neurones with increasing frequency and significantly correlated activity (32,2%); early and late neurones with increasing frequency and non significantly correlated acitivty (44,1%). 5. The activity of most of the NBSE and NPBE with increasing frequency is significantly correlated with the duration of the expiration. Among the MLE and NPBE with a decreasing frequency, a great number of neurones are not significantly correlated. 6. The functional significantion of the different neuronal types is discussed from these correlation tests and from the pattern of activity and axonal pathways.", "contents": "[Function of different medullary neurons in respiration]. 1. We have studied the activity of 162 medullary respiratory neurones in the \"encephale isole bas\" cat. These neurones were classed into three groups : bulbospinal inspiratory (NBSI : 39) or expiratory (NBSE : 15) neurones whose axons enter the spinal cord ; inspiratory or expiratory laryngeal motoneurones (MLI : 17; MLE : 10) antidromically activated by vagus nerve stimulation ; propriobulbar inspiratory (NPBI : 59) or expiratory (NPBE : 22) neurones whose axons lie perhaps entirely within the medulla. 2. Correlation coefficients between number of spikes delivered in each burst and the duration of the corresponding respiratory phase (inspiration for NBSI, MLI, NPBI ; expiration for NBSE, MLE, NPBE) have been calculated for each neurone. 3. The activity of most of the NBSI and MLI is significantly correlated with the duration of the inspiration. These two groups of neurones are probably homogenous. 4. On the basis of this correlation test, NPBI do not constitute an homogeneous population ; 50% of NPBI are not significantly correlated. The same results are obtained if correlations are calculated between the number of spikes delivered and the amplitude of integrated phrenic nerve acitivty. According to the discharge pattern and correlation test, we can consider three groups of NPBI : early recruited neurones with decreasing frequency and non significantly correlated activity (23,7%); early and late neurones with increasing frequency and significantly correlated activity (32,2%); early and late neurones with increasing frequency and non significantly correlated acitivty (44,1%). 5. The activity of most of the NBSE and NPBE with increasing frequency is significantly correlated with the duration of the expiration. Among the MLE and NPBE with a decreasing frequency, a great number of neurones are not significantly correlated. 6. The functional significantion of the different neuronal types is discussed from these correlation tests and from the pattern of activity and axonal pathways."} {"id": "PMID:1263146", "title": "Transfer characteristics between EMG activity and muscle tension under isometric conditions in man.", "content": "The relationship between motor unit activity and a voluntarily produced, sinusoidally modulated isometric tension was evaluated as a function of the modulation frequency. These date are reported in terms of the gain and phase difference of the motor activity (input) and tension (output) relationship, the gain being the logarithmic ratio of the amplitudes of the output and input sinusoids. It was found that an increase in the modulation amplitude of the motor unit activity was required to produce the same amount of modulation of the output tension as the modulation frequency was increased. For example, the modulation amplitude of the activity is about twice as much at 2 Hz as at 0.25 Hz and about 4 times as much at 5 Hz. It was also found that the maximum tension which could be produced voluntarily during brief jerks at 5 Hz was the same as the maximum sustained tension which could be attained. This latter finding emphasizes the importance of recruitment and especially synchronization of motor unit activity to the gradation of output tension.", "contents": "Transfer characteristics between EMG activity and muscle tension under isometric conditions in man. The relationship between motor unit activity and a voluntarily produced, sinusoidally modulated isometric tension was evaluated as a function of the modulation frequency. These date are reported in terms of the gain and phase difference of the motor activity (input) and tension (output) relationship, the gain being the logarithmic ratio of the amplitudes of the output and input sinusoids. It was found that an increase in the modulation amplitude of the motor unit activity was required to produce the same amount of modulation of the output tension as the modulation frequency was increased. For example, the modulation amplitude of the activity is about twice as much at 2 Hz as at 0.25 Hz and about 4 times as much at 5 Hz. It was also found that the maximum tension which could be produced voluntarily during brief jerks at 5 Hz was the same as the maximum sustained tension which could be attained. This latter finding emphasizes the importance of recruitment and especially synchronization of motor unit activity to the gradation of output tension."} {"id": "PMID:1263147", "title": "Risky and safe contraceptors: some personality factors.", "content": "Female university students (N = 191) categorized as users of risky or safe contraceptives were compared on the following personality measures: Rotter's Internal-External Scale, Cantril's Self-Anchoring Striving Scale, Rosen's Value Orientation Scale, and Srole's Anomie Scale. Safe contraceptors had significantly higher levels of striving for the present and for five years hence than risky contraceptors. There were no significant differences between the two groups on the remaining measures.", "contents": "Risky and safe contraceptors: some personality factors. Female university students (N = 191) categorized as users of risky or safe contraceptives were compared on the following personality measures: Rotter's Internal-External Scale, Cantril's Self-Anchoring Striving Scale, Rosen's Value Orientation Scale, and Srole's Anomie Scale. Safe contraceptors had significantly higher levels of striving for the present and for five years hence than risky contraceptors. There were no significant differences between the two groups on the remaining measures."} {"id": "PMID:1263148", "title": "Internal-external control, interpersonal trust, and the motive to avoid success in college women.", "content": "The Internal-External Control scale, Interpersonal Trust scale, and an assessment of the Motive To Avoid Success were administered to 86 undergraduate women. As expected, external and low trust scores covaried with comparatively high levels of achievement-related anxiety. The results were interpreted in terms of possible repression tendencies of internal subjects and the defensive properties inherent in the external and low trust belief systems.", "contents": "Internal-external control, interpersonal trust, and the motive to avoid success in college women. The Internal-External Control scale, Interpersonal Trust scale, and an assessment of the Motive To Avoid Success were administered to 86 undergraduate women. As expected, external and low trust scores covaried with comparatively high levels of achievement-related anxiety. The results were interpreted in terms of possible repression tendencies of internal subjects and the defensive properties inherent in the external and low trust belief systems."} {"id": "PMID:1263149", "title": "Is internal-external control an age-related variable?", "content": "Following the suggestion proposed by Duke, Shaheen, and Nowicki, this study was designed to test the basic hypothesis that the meaning of internal-external control (I-E) may differ with age. Such variables as age, educational level, socioeconomic status, self-confidence, etc., which have consistently been found to relate to I-E for children through college age Ss, were examined to see if these bear a relationship to I-E for a group of parents (95 fathers and 107 mothers) of college students (father mean age 48, mother mean age 46). Results indicated that with the exception of father education, there was no significant relationship between I-E and all other variables. Thus, these findings support the notion that I-E is an age-related variable, that generalizations from previous studies to older people should be re-evaluated, and that future research should study the meaning and dynamics of I-E for older people.", "contents": "Is internal-external control an age-related variable? Following the suggestion proposed by Duke, Shaheen, and Nowicki, this study was designed to test the basic hypothesis that the meaning of internal-external control (I-E) may differ with age. Such variables as age, educational level, socioeconomic status, self-confidence, etc., which have consistently been found to relate to I-E for children through college age Ss, were examined to see if these bear a relationship to I-E for a group of parents (95 fathers and 107 mothers) of college students (father mean age 48, mother mean age 46). Results indicated that with the exception of father education, there was no significant relationship between I-E and all other variables. Thus, these findings support the notion that I-E is an age-related variable, that generalizations from previous studies to older people should be re-evaluated, and that future research should study the meaning and dynamics of I-E for older people."} {"id": "PMID:1263150", "title": "Components of suicidal intent in completed and attempted suicides.", "content": "An objective suicidal intent scale was completed for 235 completed suicides and 246 attempted suicides in Philadelphia. The responses to the items of the suicidal intent scale were factor analyzed separately for the two groups, and the pattern of factors compared. The major difference centered around communication. For the completed suicide the decision appears to be whether or not to communicate; for the attempted suicide the decision appears to be when to communicate.", "contents": "Components of suicidal intent in completed and attempted suicides. An objective suicidal intent scale was completed for 235 completed suicides and 246 attempted suicides in Philadelphia. The responses to the items of the suicidal intent scale were factor analyzed separately for the two groups, and the pattern of factors compared. The major difference centered around communication. For the completed suicide the decision appears to be whether or not to communicate; for the attempted suicide the decision appears to be when to communicate."} {"id": "PMID:1263151", "title": "On the question of pre-existing personality differences between users and nonusers of drugs.", "content": "This study represents a beginning attempt to investigate the possible existence of predrug usage, personality differences between users and nonusers of drugs. Ss were male college students: 30 heavy marijuana (multiple drug) users, 30 light marijuana users, and 30 nonusers were compared on the results of the Gordon Personal Profile administered prior to the use of any drugs. Significant differences were found on two of the personality scales on this instrument.", "contents": "On the question of pre-existing personality differences between users and nonusers of drugs. This study represents a beginning attempt to investigate the possible existence of predrug usage, personality differences between users and nonusers of drugs. Ss were male college students: 30 heavy marijuana (multiple drug) users, 30 light marijuana users, and 30 nonusers were compared on the results of the Gordon Personal Profile administered prior to the use of any drugs. Significant differences were found on two of the personality scales on this instrument."} {"id": "PMID:1263152", "title": "Suicidal age and childhood onychophagia among veterans with personality disorders.", "content": "The relationship between childhood onychophagia (finger-nail biting) and the mean age of suicidal and nonsuicidal veterans was investigated among 70 V.A. hospitalized males, diagnosed as personality disorders. The results show that the mean age of suicidal veterans was significantly lower than that of nonsuicidal veterans, and the childhood onychophagia variable, \"focal suicide,\" significantly lowered the mean age of suicidal veterans, but did not significantly lower the mean age of nonsuicidal veterans.", "contents": "Suicidal age and childhood onychophagia among veterans with personality disorders. The relationship between childhood onychophagia (finger-nail biting) and the mean age of suicidal and nonsuicidal veterans was investigated among 70 V.A. hospitalized males, diagnosed as personality disorders. The results show that the mean age of suicidal veterans was significantly lower than that of nonsuicidal veterans, and the childhood onychophagia variable, \"focal suicide,\" significantly lowered the mean age of suicidal veterans, but did not significantly lower the mean age of nonsuicidal veterans."} {"id": "PMID:1263153", "title": "A discrepancy between two modes of haptic length perception.", "content": "This study investigated the possibility that systematic differences exist between the perceptions resulting from the use of two different heptic modes to know the same object. In each of three experiments 24 male and female college students chose visual comparison stimuli to match the length of haptically presented standard stimuli. In each experiment significantly smaller visual matches were made when the length of the haptic standard was perceived by holding it between the thumb and index finger than when the haptic standard was perceived by stroking it from end to end with the index finger. Experiment 1 established a significant difference (p less than .05) using a horizontal visual comparison. Experiment 2 replicated this effect (p less than .001) using vertical visual comparisons. Experiment 3 again replicated the effect (p less than .001) with visual comparisons and ruled out the possibility that the effect was due to the orientation of the haptic stimuli.", "contents": "A discrepancy between two modes of haptic length perception. This study investigated the possibility that systematic differences exist between the perceptions resulting from the use of two different heptic modes to know the same object. In each of three experiments 24 male and female college students chose visual comparison stimuli to match the length of haptically presented standard stimuli. In each experiment significantly smaller visual matches were made when the length of the haptic standard was perceived by holding it between the thumb and index finger than when the haptic standard was perceived by stroking it from end to end with the index finger. Experiment 1 established a significant difference (p less than .05) using a horizontal visual comparison. Experiment 2 replicated this effect (p less than .001) using vertical visual comparisons. Experiment 3 again replicated the effect (p less than .001) with visual comparisons and ruled out the possibility that the effect was due to the orientation of the haptic stimuli."} {"id": "PMID:1263154", "title": "The effects of experimentally induced changes in self-concept on associative learning.", "content": "It has been hypothesized that self-concept influences ability to learn. This experiment systematically manipulated the self-concepts of learners regarding their abilities to learn a foreign language and measured their subsequent learning of a synthetic foreign language vocabulary list. Eleven Ss were randomly assigned to each of three groups: self-concept raised, self-concept lowered, control. Ss were college freshman who were not enrolled in a foreign language course or had not previously taken more than one semester of a foreign language. Self-concepts were measured as self-description of ability to learn a foreign language. Self-concepts were raised or lowered by providing false scores on a foreign language aptitude test. Learning was measured as performance on a paired-associates task utilizing random shapes and CVCs. Ss with lowered self-concepts learned more slowly than control Ss or Ss with raised self-concepts.", "contents": "The effects of experimentally induced changes in self-concept on associative learning. It has been hypothesized that self-concept influences ability to learn. This experiment systematically manipulated the self-concepts of learners regarding their abilities to learn a foreign language and measured their subsequent learning of a synthetic foreign language vocabulary list. Eleven Ss were randomly assigned to each of three groups: self-concept raised, self-concept lowered, control. Ss were college freshman who were not enrolled in a foreign language course or had not previously taken more than one semester of a foreign language. Self-concepts were measured as self-description of ability to learn a foreign language. Self-concepts were raised or lowered by providing false scores on a foreign language aptitude test. Learning was measured as performance on a paired-associates task utilizing random shapes and CVCs. Ss with lowered self-concepts learned more slowly than control Ss or Ss with raised self-concepts."} {"id": "PMID:1263155", "title": "Encoding and decoding of connected discourse during altered states of consciousness.", "content": "The following hypotheses were investigated in a study of memory recall and an altered state of consciousness: (a) A direct relationship was expected between the magnitude of correct responses and task complexity. (b) Semantic context variation was expected to cause greater impairment in verbal processing than variation in syntactic constraints. (c) Under N2O fewer correct responses in verbal processing were expected to be made. Forty-four volunteers, male corpsmen in the U. S. Navy between the ages of 20 and 29, were randomly divided into two equal groups: a nitrous oxide group and an air group. After breathing either N2O or air for 10 minutes, Ss were required to repeat pairs of taped sentences of high syntax/high semantic context to low syntax/low semantic context. Responses were scored for errors. All three hypotheses were accepted. Task complexity caused the greatest magnitude of errors. Ss were able to compensate for variations in syntax and in the gas state, but low semantic quality strongly affected performance. The factors interacted in powerful ways to produce differential response errors from a low error rate for air/high syntax/high context to a high error rate for N2O/low syntax/low context.", "contents": "Encoding and decoding of connected discourse during altered states of consciousness. The following hypotheses were investigated in a study of memory recall and an altered state of consciousness: (a) A direct relationship was expected between the magnitude of correct responses and task complexity. (b) Semantic context variation was expected to cause greater impairment in verbal processing than variation in syntactic constraints. (c) Under N2O fewer correct responses in verbal processing were expected to be made. Forty-four volunteers, male corpsmen in the U. S. Navy between the ages of 20 and 29, were randomly divided into two equal groups: a nitrous oxide group and an air group. After breathing either N2O or air for 10 minutes, Ss were required to repeat pairs of taped sentences of high syntax/high semantic context to low syntax/low semantic context. Responses were scored for errors. All three hypotheses were accepted. Task complexity caused the greatest magnitude of errors. Ss were able to compensate for variations in syntax and in the gas state, but low semantic quality strongly affected performance. The factors interacted in powerful ways to produce differential response errors from a low error rate for air/high syntax/high context to a high error rate for N2O/low syntax/low context."} {"id": "PMID:1263174", "title": "The control of hypertension, atherosclerotic diseases, and diabetes in a family practice.", "content": "A community-orientated programme for the control of hypertension, atherosclerotic disease, and diabetes has been developed in a family practice in a neighbourhood of Jerusalem. Intervention is directed mainly towards the control of risk factors associated with these diseases.The programme has specific objectives for diet, smoking, obesity, blood pressure, serum cholesterol, glucose intolerance, and diabetes mellitus, and the identification and treatment of patients with cardiovascular diseases. The survey seeks to identify the nature and extent of problems, intervention by medicinal and educational means, and continuing surveillance and evaluation.The programme aims to test and demonstrate the feasibility of carrying out multifactorial community health care within the framework of a family practice, thereby developing a joint practice of primary health care and community medicine.", "contents": "The control of hypertension, atherosclerotic diseases, and diabetes in a family practice. A community-orientated programme for the control of hypertension, atherosclerotic disease, and diabetes has been developed in a family practice in a neighbourhood of Jerusalem. Intervention is directed mainly towards the control of risk factors associated with these diseases.The programme has specific objectives for diet, smoking, obesity, blood pressure, serum cholesterol, glucose intolerance, and diabetes mellitus, and the identification and treatment of patients with cardiovascular diseases. The survey seeks to identify the nature and extent of problems, intervention by medicinal and educational means, and continuing surveillance and evaluation.The programme aims to test and demonstrate the feasibility of carrying out multifactorial community health care within the framework of a family practice, thereby developing a joint practice of primary health care and community medicine."} {"id": "PMID:1263175", "title": "High blood pressure and psychiatric disorder in general practice.", "content": "A programme for the control of hypertension has been started in general practice with the principal aim of finding the most effective way of identifying and keeping patients with high blood pressure under continuing control. One objective is to determine the psychiatric state of hypertensive patients in the programme and this paper reports these results.There was no significant difference between the percentage of psychiatric patients in a hypertensive group and a control group. There was no relationship between blood pressure recorded at the initial clinic and the psychiatric state. In both hypertensive and control groups, patients who were on hypertensive treatment at the initial clinic were more likely to be ;psychiatric' than those who were not on treatment; this appears to be less likely to occur if the hypertension is controlled.", "contents": "High blood pressure and psychiatric disorder in general practice. A programme for the control of hypertension has been started in general practice with the principal aim of finding the most effective way of identifying and keeping patients with high blood pressure under continuing control. One objective is to determine the psychiatric state of hypertensive patients in the programme and this paper reports these results.There was no significant difference between the percentage of psychiatric patients in a hypertensive group and a control group. There was no relationship between blood pressure recorded at the initial clinic and the psychiatric state. In both hypertensive and control groups, patients who were on hypertensive treatment at the initial clinic were more likely to be ;psychiatric' than those who were not on treatment; this appears to be less likely to occur if the hypertension is controlled."} {"id": "PMID:1263176", "title": "An experimental collection service for pathology specimens.", "content": "The use of laboratory services made by a group of general practitioners was compared before, during and after the provision of a free collection service for transporting specimens and results between the practices and the laboratory.In comparison with the use of a control group of general practitioners, the study group made a sharply increased use of the laboratory during the 33-week survey period. In addition, both the practices. The laboratory staff welcomed the service.", "contents": "An experimental collection service for pathology specimens. The use of laboratory services made by a group of general practitioners was compared before, during and after the provision of a free collection service for transporting specimens and results between the practices and the laboratory.In comparison with the use of a control group of general practitioners, the study group made a sharply increased use of the laboratory during the 33-week survey period. In addition, both the practices. The laboratory staff welcomed the service."} {"id": "PMID:1263177", "title": "Folate supplements during pregnancy.", "content": "In a controlled, prospective trial, the effects of giving ferrous sulphate 50 mg daily to 76 pregnant women was compared with giving ferrous sulphate 50 mg daily plus folic acid 0.5 mg daily to 82 women in 12 general practices in South-east England.No differences in obstetric complications were found between the two groups, although the evidence of some of the listed complications may be too rare for detection in a sample of patients of this size.", "contents": "Folate supplements during pregnancy. In a controlled, prospective trial, the effects of giving ferrous sulphate 50 mg daily to 76 pregnant women was compared with giving ferrous sulphate 50 mg daily plus folic acid 0.5 mg daily to 82 women in 12 general practices in South-east England.No differences in obstetric complications were found between the two groups, although the evidence of some of the listed complications may be too rare for detection in a sample of patients of this size."} {"id": "PMID:1263179", "title": "Salpingitis: a frequent response to intrauterine contraception.", "content": "Nonbacterial, chronic salpingitis was found in less than 1% of non-IUD users undergoing elective tubal sterilization, Nonbacterial, chronic salpingitis was found in 47% of IUD users undergoing elective sterilization. Speculation about the influence of this finding on inflammatory morbidity is presented.", "contents": "Salpingitis: a frequent response to intrauterine contraception. Nonbacterial, chronic salpingitis was found in less than 1% of non-IUD users undergoing elective tubal sterilization, Nonbacterial, chronic salpingitis was found in 47% of IUD users undergoing elective sterilization. Speculation about the influence of this finding on inflammatory morbidity is presented."} {"id": "PMID:1263180", "title": "Fimbrial microbiopsy.", "content": "Microbiopsies from the fimbrial surface were obtained from 70 women to determine the percentage of ciliated cells. The following observations were made: 1. There is a close correlation between the percentages of ciliated cells in each of the two oviducts; 2. The percentages of ciliated cells in normal, fertile women vary between 54 and 70 with no apparent variation between the follicular and luteal phases of the cycle; 3. The percentage of ciliated cells is reduced in hypoestrogenic amenorrhea, during pregnancy and during steroid contraception; 4. Ovarian endometriosis without tubal involvement is usually not associated with fimbrial reciliation, but sequelae of pelvic inflammatory disease can be associated with deciliation of the fimbrial surface; 5. Two cases are reported in which the fimbrial surface showed extreme deciliation in association with sqamous metaplasia of the epithelium, possibly indicating defective ovum transport over the fimbrial surface.", "contents": "Fimbrial microbiopsy. Microbiopsies from the fimbrial surface were obtained from 70 women to determine the percentage of ciliated cells. The following observations were made: 1. There is a close correlation between the percentages of ciliated cells in each of the two oviducts; 2. The percentages of ciliated cells in normal, fertile women vary between 54 and 70 with no apparent variation between the follicular and luteal phases of the cycle; 3. The percentage of ciliated cells is reduced in hypoestrogenic amenorrhea, during pregnancy and during steroid contraception; 4. Ovarian endometriosis without tubal involvement is usually not associated with fimbrial reciliation, but sequelae of pelvic inflammatory disease can be associated with deciliation of the fimbrial surface; 5. Two cases are reported in which the fimbrial surface showed extreme deciliation in association with sqamous metaplasia of the epithelium, possibly indicating defective ovum transport over the fimbrial surface."} {"id": "PMID:1263190", "title": "The control of ticks, fleas and lice on dogs by means of a Sendran--impregnated collar.", "content": "Plastic collars impregnated with 9,4% Sendran effectively controlled adult Rhipicephalus sanguineus for a period of 49 days and immature ticks for a period possibly in excess of 70 days when fitted to four dogs. Four uncollared dogs served as controls. Although flea burdens were extremely low the collars were apparently effective for a period in excess of 70 days. A medicated collar killed all the ticks, fleas and lice on a severely parasited dog within a period of 48 hours.", "contents": "The control of ticks, fleas and lice on dogs by means of a Sendran--impregnated collar. Plastic collars impregnated with 9,4% Sendran effectively controlled adult Rhipicephalus sanguineus for a period of 49 days and immature ticks for a period possibly in excess of 70 days when fitted to four dogs. Four uncollared dogs served as controls. Although flea burdens were extremely low the collars were apparently effective for a period in excess of 70 days. A medicated collar killed all the ticks, fleas and lice on a severely parasited dog within a period of 48 hours."} {"id": "PMID:1263191", "title": "Studies on the life cycle of the lungworm, Pneumostrongylus calcaratus, M\u00f6nnig, 1932.", "content": "The morphology of the first, second and third stage larvae of Pneumostrongylus calcaratus is described. Greater numbers of larvae were present in experimentally than in naturally infested slugs. An attempt to transmit infestation to impala was unsuccessful.", "contents": "Studies on the life cycle of the lungworm, Pneumostrongylus calcaratus, M\u00f6nnig, 1932. The morphology of the first, second and third stage larvae of Pneumostrongylus calcaratus is described. Greater numbers of larvae were present in experimentally than in naturally infested slugs. An attempt to transmit infestation to impala was unsuccessful."} {"id": "PMID:1263192", "title": "Preliminary report on the intermandibular cutaneous glandular area and the infraorbital gland of the steenbok.", "content": "An intermandibular glandular area, never before described in any other ungulate has been found in the steenbok (Raphicerus campestris). It consists of enlarged sebaceous and apocrine sweat glands situated in the upper two-thirds of the dermis. They produce a dirty white almost flaky odoriferous substance which clings to the hairs of the area and is easily rubbed off for marking territorial areas as well as for marking females during mating. The infraorbital gland produces a black secretion which is the combined secretion of melanaceous, branched alveolar, sebaceous and enlarged apocrine sweat glands. The function of this secretion is not known as it is not used for any obvious marking purposes.", "contents": "Preliminary report on the intermandibular cutaneous glandular area and the infraorbital gland of the steenbok. An intermandibular glandular area, never before described in any other ungulate has been found in the steenbok (Raphicerus campestris). It consists of enlarged sebaceous and apocrine sweat glands situated in the upper two-thirds of the dermis. They produce a dirty white almost flaky odoriferous substance which clings to the hairs of the area and is easily rubbed off for marking territorial areas as well as for marking females during mating. The infraorbital gland produces a black secretion which is the combined secretion of melanaceous, branched alveolar, sebaceous and enlarged apocrine sweat glands. The function of this secretion is not known as it is not used for any obvious marking purposes."} {"id": "PMID:1263194", "title": "Cryptococcosis in a dog.", "content": "A report is presented of a fatal systemic Cryptococcus noeformans infection involving the central nervous system of a dog and complicated by a concurrent infection of the brain and splene by an unidentified filamentous fungus resembling a Paecilomyces spp. The literature on cryptococcosis in domestic animals is briefly reviewed.", "contents": "Cryptococcosis in a dog. A report is presented of a fatal systemic Cryptococcus noeformans infection involving the central nervous system of a dog and complicated by a concurrent infection of the brain and splene by an unidentified filamentous fungus resembling a Paecilomyces spp. The literature on cryptococcosis in domestic animals is briefly reviewed."} {"id": "PMID:1263196", "title": "Congenital diaphragmatic hiatus in a dog.", "content": "The symptoms and post mortem findings of a case of diaphragmatic hiatus in a dog are described. At necropsy the caudate and right lateral lobes of the liver, the pyloric portion of the stomach, most of the small intestine and large intestines, the spleen, pancreas and omentum were found in the thoracic cavity.", "contents": "Congenital diaphragmatic hiatus in a dog. The symptoms and post mortem findings of a case of diaphragmatic hiatus in a dog are described. At necropsy the caudate and right lateral lobes of the liver, the pyloric portion of the stomach, most of the small intestine and large intestines, the spleen, pancreas and omentum were found in the thoracic cavity."} {"id": "PMID:1263197", "title": "Cordophilosis and fatal gastro-intestinal verminosis in eland.", "content": "Fatal cases of cordophilosis and gastro-intestinal verminosis in eland are reported. Some of these cases were complicated with heartwater or cytauxzoonosis. Cordophilosis resulted in acute cardiac arrest. Infestations with gastro-intestinal namatodes were responsible for extreme emaciation. Clinically affected eland responded dramatically to systemic treatment with levamisole hydrocholride.", "contents": "Cordophilosis and fatal gastro-intestinal verminosis in eland. Fatal cases of cordophilosis and gastro-intestinal verminosis in eland are reported. Some of these cases were complicated with heartwater or cytauxzoonosis. Cordophilosis resulted in acute cardiac arrest. Infestations with gastro-intestinal namatodes were responsible for extreme emaciation. Clinically affected eland responded dramatically to systemic treatment with levamisole hydrocholride."} {"id": "PMID:1263198", "title": "Myasthenia gravis in a Fox Terrier litter.", "content": "A report of a myasthenia gravis-like syndrome, which occurred in two Fox Terrier litter mates, is presented. The clinical signs which appeared within 5 weeks of birth, and the subsequent course of the disease are described. Treatment with neostigmine and atropine initially provided control. Some recognised features of the condition in dogs are briefly reviewed.", "contents": "Myasthenia gravis in a Fox Terrier litter. A report of a myasthenia gravis-like syndrome, which occurred in two Fox Terrier litter mates, is presented. The clinical signs which appeared within 5 weeks of birth, and the subsequent course of the disease are described. Treatment with neostigmine and atropine initially provided control. Some recognised features of the condition in dogs are briefly reviewed."} {"id": "PMID:1263199", "title": "Monoquaternary neuromuscular blocking agents based on 1-tetralone and 1-indanone.", "content": "The preparation of three isomeric 1-tetralone hydrozones 4 and three isomeric 1-indanone hydrozones 5 possessing a single quaternary ammonium center is described. Several of the compounds possessed significant neuromuscular blocking activity, and two approached suxamethonium in potency. 1H NMR evidence obtained from a study of the N,N-dimethylhydrozones indicated that the hydrazones adopted an E configuration in solution.", "contents": "Monoquaternary neuromuscular blocking agents based on 1-tetralone and 1-indanone. The preparation of three isomeric 1-tetralone hydrozones 4 and three isomeric 1-indanone hydrozones 5 possessing a single quaternary ammonium center is described. Several of the compounds possessed significant neuromuscular blocking activity, and two approached suxamethonium in potency. 1H NMR evidence obtained from a study of the N,N-dimethylhydrozones indicated that the hydrazones adopted an E configuration in solution."} {"id": "PMID:1263201", "title": "Substituted alpah-methylbenzyl and tricyclic arylalkyl lactamimides as inhibitors of blood platelet aggregation.", "content": "N-[1-(p-Phenoxyphenyl)ethyl]hexahydro-2H-azepin-2-imine hydrochloride (10) and N-[1-(2-dibenzothienyl)-ethyl]hexahydro-2H-azepin-2-imine hydrochloride (22) were found to inhibit in vitro aggregation of human blood platelets induced by ADP with minimal release of procoagulant platelet factor 3. The compounds were selected from a series of substituted alpha-methylbenzyl and tricyclic arylalkyl lactamimides that were free of hypoglycemic and diuretic effects. Compounds 10 and 22, as well as N-[1-(1-naphthyl)ethyl]hexahydro-2H-azepin-2-imine hydrochloride (I) and N-(2,2-diphenylpentyl)hexahydro-2H-azepin-2-imine hydrochloride (II), were evaluated for effects on ADP-induced platelet aggregation after repeated oral administration to guinea pigs. Compound II (RMI 12,366A) showed in vivo activity in this system 2 h after the last of four daily doses of 100 mg/kg po.", "contents": "Substituted alpah-methylbenzyl and tricyclic arylalkyl lactamimides as inhibitors of blood platelet aggregation. N-[1-(p-Phenoxyphenyl)ethyl]hexahydro-2H-azepin-2-imine hydrochloride (10) and N-[1-(2-dibenzothienyl)-ethyl]hexahydro-2H-azepin-2-imine hydrochloride (22) were found to inhibit in vitro aggregation of human blood platelets induced by ADP with minimal release of procoagulant platelet factor 3. The compounds were selected from a series of substituted alpha-methylbenzyl and tricyclic arylalkyl lactamimides that were free of hypoglycemic and diuretic effects. Compounds 10 and 22, as well as N-[1-(1-naphthyl)ethyl]hexahydro-2H-azepin-2-imine hydrochloride (I) and N-(2,2-diphenylpentyl)hexahydro-2H-azepin-2-imine hydrochloride (II), were evaluated for effects on ADP-induced platelet aggregation after repeated oral administration to guinea pigs. Compound II (RMI 12,366A) showed in vivo activity in this system 2 h after the last of four daily doses of 100 mg/kg po."} {"id": "PMID:1263202", "title": "Central nervous system active 5-oxo-1,4,5,6,7,8-hexahydrocinnolines.", "content": "Among a series of 5-oxo-1,4,5,6,7,8-hexahydrocinnolines examined for their CNS activity, 1-(2-diethylaminoethyl)-3-(p-fluorophenyl)-5-oxo-7,7-dimethyl-1,4,5,6,7,8-hexahydrocinnoline (23) and 1-(2-dimethylaminoethyl)-3-phenyl-5-oxo-7,7-dimethyl-1,4,5,6,7,8-hexahydrocinnoline (27) had sedative and anticonvulsant properties and were also acitve in tests used to characterize antidepressants. But their narrow safety margin precluded further follow-up studies. Derivatives 35-38 of 2-(omega-phenacyl)-3-hydrazino-5,5-dimethyl-2-cyclohexenone were active in tests used to characterize antidepressants and were weakly sedative but not anticonvulsant.", "contents": "Central nervous system active 5-oxo-1,4,5,6,7,8-hexahydrocinnolines. Among a series of 5-oxo-1,4,5,6,7,8-hexahydrocinnolines examined for their CNS activity, 1-(2-diethylaminoethyl)-3-(p-fluorophenyl)-5-oxo-7,7-dimethyl-1,4,5,6,7,8-hexahydrocinnoline (23) and 1-(2-dimethylaminoethyl)-3-phenyl-5-oxo-7,7-dimethyl-1,4,5,6,7,8-hexahydrocinnoline (27) had sedative and anticonvulsant properties and were also acitve in tests used to characterize antidepressants. But their narrow safety margin precluded further follow-up studies. Derivatives 35-38 of 2-(omega-phenacyl)-3-hydrazino-5,5-dimethyl-2-cyclohexenone were active in tests used to characterize antidepressants and were weakly sedative but not anticonvulsant."} {"id": "PMID:1263203", "title": "Circular dichroism and carbon-13 nuclear magnetic resonance spectra of (S)-5-alkyl-5-(2'-pentyl)-2-thiobarbituric acids.", "content": "The circular dichroism (CD) and carbon-13 nuclear magnetic resonance (13C NMR) spectra of (S)-5-(2'-pentyl)-2-thiobarbituric acid and several (S)-5-alkyl-5-(2'-pentyl)-2-thiobarbituric acids were obtained. The results were compared to CD and 13C NMR spectral data obtained from (S)-5-(2'-pentyl)bartituric acid and (S)-5-alkyl-5-(2'-pentyl)barbituric acids.", "contents": "Circular dichroism and carbon-13 nuclear magnetic resonance spectra of (S)-5-alkyl-5-(2'-pentyl)-2-thiobarbituric acids. The circular dichroism (CD) and carbon-13 nuclear magnetic resonance (13C NMR) spectra of (S)-5-(2'-pentyl)-2-thiobarbituric acid and several (S)-5-alkyl-5-(2'-pentyl)-2-thiobarbituric acids were obtained. The results were compared to CD and 13C NMR spectral data obtained from (S)-5-(2'-pentyl)bartituric acid and (S)-5-alkyl-5-(2'-pentyl)barbituric acids."} {"id": "PMID:1263204", "title": "Syntheses of heterocylic fused thiazole acetic acids. 2.", "content": "A number of tricyclic and bicyclic fused thiazole-2-acetic acid derivatives were prepared and the chemistry and biological properties of these compounds are discussed. Many of the esters exhibited antitubercular activity. The bicyclic thiazole-2-acetic acids had antidepressant activity. Interesting antimetastatic activity against Lewis lung tumor in mice was found with several compounds, in particular, the thiazolo[3,2-a]benzimidazole-2-acetic acid derivative XI.", "contents": "Syntheses of heterocylic fused thiazole acetic acids. 2. A number of tricyclic and bicyclic fused thiazole-2-acetic acid derivatives were prepared and the chemistry and biological properties of these compounds are discussed. Many of the esters exhibited antitubercular activity. The bicyclic thiazole-2-acetic acids had antidepressant activity. Interesting antimetastatic activity against Lewis lung tumor in mice was found with several compounds, in particular, the thiazolo[3,2-a]benzimidazole-2-acetic acid derivative XI."} {"id": "PMID:1263205", "title": "(Vinylaryloxy)acetic acids. A new class of diuretic agents. 1. (Diacylvinylaryloxy)acetic acids.", "content": "A series of (diacylvinylaryloxy)acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. Several compounds exhibit a high order of activity, the most active being [2,3-dichloro-4-(2,2-diacetylvinyl)-phenoxy]acetic acid (3). This compound is about three times as potent as [2,3-dichloro-4-(2-methylenebutyryl)-phenoxy]acetic acid (ethacrynic acid) but is qualitatively similar in causing a prompt increase in the excretion of water and in the excretion of sodium and chloride ions in approximately equimolar amounts. Saturation of the double bond of 3 virtually abolishes activity lending support to the hypothesis that the saluresis induced by these compounds, like that of ethacrynic acid, is related at least in part to a chemical reaction with protein-bound sulfhydryl groups. Four mercaptan adducts of 3 were prepared; these probably function as prodrugs in producing saluresis. The adduct with mercaptoacetic acid is as active as 3 itself.", "contents": "(Vinylaryloxy)acetic acids. A new class of diuretic agents. 1. (Diacylvinylaryloxy)acetic acids. A series of (diacylvinylaryloxy)acetic acids was synthesized and tested in dogs for saluretic and diuretic activity. Several compounds exhibit a high order of activity, the most active being [2,3-dichloro-4-(2,2-diacetylvinyl)-phenoxy]acetic acid (3). This compound is about three times as potent as [2,3-dichloro-4-(2-methylenebutyryl)-phenoxy]acetic acid (ethacrynic acid) but is qualitatively similar in causing a prompt increase in the excretion of water and in the excretion of sodium and chloride ions in approximately equimolar amounts. Saturation of the double bond of 3 virtually abolishes activity lending support to the hypothesis that the saluresis induced by these compounds, like that of ethacrynic acid, is related at least in part to a chemical reaction with protein-bound sulfhydryl groups. Four mercaptan adducts of 3 were prepared; these probably function as prodrugs in producing saluresis. The adduct with mercaptoacetic acid is as active as 3 itself."} {"id": "PMID:1263206", "title": "Biologically active polycycloalkanes. 2. Antiviral 4-homoisotwistane derivatives.", "content": "New derivatives of 4-homoisotwistane (tricyclo[5.3.1.0(3,8)]undecane) (3), the olefin (8), bromide (4), alcohols (7,9,11, and 14), ketone (10), acid (12), esters (13, 18a, and 18b), amides (5, 16, and 19a-d), nitrile (20), and amines and their hydrochlorides (6, 17, and 21), were prepared, and antiviral activities of these compounds were determined in vitro on a monolayer culture of chick embryo fibroblasts against Newcastle disease virus. 4-Homoisotwist-3-ylamine hydrochloride (6) and 4-homoisotwist-3-ylmethylamine hydrochloride (21) were found 30-50 times more potent than amantadine hydrochloride in this assay. Methods of preparing the test compounds included those functionalization reactions of 3 which revealed many interesting features of the reactivity of the recently discovered polycyclic hydrocarbon 3.", "contents": "Biologically active polycycloalkanes. 2. Antiviral 4-homoisotwistane derivatives. New derivatives of 4-homoisotwistane (tricyclo[5.3.1.0(3,8)]undecane) (3), the olefin (8), bromide (4), alcohols (7,9,11, and 14), ketone (10), acid (12), esters (13, 18a, and 18b), amides (5, 16, and 19a-d), nitrile (20), and amines and their hydrochlorides (6, 17, and 21), were prepared, and antiviral activities of these compounds were determined in vitro on a monolayer culture of chick embryo fibroblasts against Newcastle disease virus. 4-Homoisotwist-3-ylamine hydrochloride (6) and 4-homoisotwist-3-ylmethylamine hydrochloride (21) were found 30-50 times more potent than amantadine hydrochloride in this assay. Methods of preparing the test compounds included those functionalization reactions of 3 which revealed many interesting features of the reactivity of the recently discovered polycyclic hydrocarbon 3."} {"id": "PMID:1263207", "title": "Local anesthetics. 2-Diethylamino-2',6'-acylxylidides.", "content": "A series of C-alkylated derivatives of lidocaine has been synthesized, and the local anesthetic potencies were determined. Activity reached a miximum with the butyroxylidide (alpha-ethyl group), but toxicity increased regularly with the number of carboons in the side chain. Spectral data showed the compounds to exist as associated H-bonded structures, the free base most likely as intramolecularly bonded trans amides and the hydrochlorides most likely as associated cis amindes.", "contents": "Local anesthetics. 2-Diethylamino-2',6'-acylxylidides. A series of C-alkylated derivatives of lidocaine has been synthesized, and the local anesthetic potencies were determined. Activity reached a miximum with the butyroxylidide (alpha-ethyl group), but toxicity increased regularly with the number of carboons in the side chain. Spectral data showed the compounds to exist as associated H-bonded structures, the free base most likely as intramolecularly bonded trans amides and the hydrochlorides most likely as associated cis amindes."} {"id": "PMID:1263208", "title": "(Vinylaryloxy)acetic acids. A new class of diuretic agents. 2. (4-(3-Oxo-1-alkenyl)phenoxy)acetic acids.", "content": "A series of (E)-[4-(3-oxo-1-alkenyl)phenoxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic properties. Several compounds exhibited noteworthy activity, e.g., (E)-[2,3-dichloro-4-(3-oxo-1-butenyl)phenoxy]acetic acid (3a). While possessing only half of the dose potency of ethacrynic acid (2), the active compounds act similarly to this diuretic in causing a prompt increase in the excretion of water and in the excretion of sodium and chloride ions in approximately equimolar amounts. Potassium ion excretion is increased but less markedly than sodium excretion.", "contents": "(Vinylaryloxy)acetic acids. A new class of diuretic agents. 2. (4-(3-Oxo-1-alkenyl)phenoxy)acetic acids. A series of (E)-[4-(3-oxo-1-alkenyl)phenoxy]acetic acids was synthesized and tested in dogs for saluretic and diuretic properties. Several compounds exhibited noteworthy activity, e.g., (E)-[2,3-dichloro-4-(3-oxo-1-butenyl)phenoxy]acetic acid (3a). While possessing only half of the dose potency of ethacrynic acid (2), the active compounds act similarly to this diuretic in causing a prompt increase in the excretion of water and in the excretion of sodium and chloride ions in approximately equimolar amounts. Potassium ion excretion is increased but less markedly than sodium excretion."} {"id": "PMID:1263227", "title": "The Rockford School of Medicine undergraduate quality assurance program.", "content": "An undergraduate program of ambulatory care quality assurance has been operational at the Rockford School of Medicine for three years. The original intent of the program was to increase the acceptance of quality assurance activities among student physicians, inculcating in them the importance of peer review at an early stage in professional development. The program experience is described, results of preliminary evaluation reported, and generalizations offered. Activities in the first year of a hospital care quality assurance program are described.", "contents": "The Rockford School of Medicine undergraduate quality assurance program. An undergraduate program of ambulatory care quality assurance has been operational at the Rockford School of Medicine for three years. The original intent of the program was to increase the acceptance of quality assurance activities among student physicians, inculcating in them the importance of peer review at an early stage in professional development. The program experience is described, results of preliminary evaluation reported, and generalizations offered. Activities in the first year of a hospital care quality assurance program are described."} {"id": "PMID:1263228", "title": "Teaching peer review at Michigan State University.", "content": "Two groups of students at Michigan State University participated in an exercise intended to teach them the process of peer review. Neither group of students completed the exercise beyond the initial steps. The authors discuss the concerns of the students and make suggestions for implementing a program of peer review in undergraduate medical school curricula.", "contents": "Teaching peer review at Michigan State University. Two groups of students at Michigan State University participated in an exercise intended to teach them the process of peer review. Neither group of students completed the exercise beyond the initial steps. The authors discuss the concerns of the students and make suggestions for implementing a program of peer review in undergraduate medical school curricula."} {"id": "PMID:1263229", "title": "Comparison of a private family practice and a university teaching practice.", "content": "In March 1972 a private family practice in Hamilton, Canada, became a teaching practice of McMaster University. Subsequently a before-and-after study was conducted to compare characteristics of the patients and the impact of the change on the practice. There was a 34 percent reduction in practice size. There was a shift to younger patients and a substantial drop in mean patient income. Utilization rates of health services rose, particularly hospitalization, even though the average length of stay decreased. Profiles of complaints and diagnoses remained very similar. Quality of care scores were comparable with those of community controls before and after the change. Gross income from clinical earnings dropped, but the amounts per person per year were very similar in the two periods. It is concluded that the \"transplanted private practice\" which becomes part of a school of medicine is a realistic teaching resource in primary care.", "contents": "Comparison of a private family practice and a university teaching practice. In March 1972 a private family practice in Hamilton, Canada, became a teaching practice of McMaster University. Subsequently a before-and-after study was conducted to compare characteristics of the patients and the impact of the change on the practice. There was a 34 percent reduction in practice size. There was a shift to younger patients and a substantial drop in mean patient income. Utilization rates of health services rose, particularly hospitalization, even though the average length of stay decreased. Profiles of complaints and diagnoses remained very similar. Quality of care scores were comparable with those of community controls before and after the change. Gross income from clinical earnings dropped, but the amounts per person per year were very similar in the two periods. It is concluded that the \"transplanted private practice\" which becomes part of a school of medicine is a realistic teaching resource in primary care."} {"id": "PMID:1263230", "title": "A model for the improvement of medical faculty lecturing.", "content": "The development of a program designed to improve the teaching effectiveness of faculty members of a new Introductory Psychopathology course at the University of Washington School of Medicine is described. Two consultants from the Office of Research in Medical Education worked closely with the faculty in designing the evaluation program during the preparation of the course. The literature on lecture effectiveness is reviewed, as are existing instructional evaluation instruments. The integration of this information and the needs of the involved faculty produced a lecture observation schedule designed to facilitate the observation of a lecture and the immediate feedback which followed each of the 15 lectures evaluated. The process of using this instrument to assist the faculty in self-improvement is discussed. While the specific evaluation method described may not be appropriate for all situations, it may serve as a model for the development of similar programs in other settings.", "contents": "A model for the improvement of medical faculty lecturing. The development of a program designed to improve the teaching effectiveness of faculty members of a new Introductory Psychopathology course at the University of Washington School of Medicine is described. Two consultants from the Office of Research in Medical Education worked closely with the faculty in designing the evaluation program during the preparation of the course. The literature on lecture effectiveness is reviewed, as are existing instructional evaluation instruments. The integration of this information and the needs of the involved faculty produced a lecture observation schedule designed to facilitate the observation of a lecture and the immediate feedback which followed each of the 15 lectures evaluated. The process of using this instrument to assist the faculty in self-improvement is discussed. While the specific evaluation method described may not be appropriate for all situations, it may serve as a model for the development of similar programs in other settings."} {"id": "PMID:1263245", "title": "Effects of selected herbicides and plant hormones on Prototheca wickerhamii.", "content": "Prototheca wickerhamii was treated in vitro with 11 different herbicides and plant hormones. Growth was inhibited by indolyl-3-acetic acid, indolyl-3-butyric acid and indolyl-3-propionic acid at 400 mug per ml. Coconut milk was stimulatory.", "contents": "Effects of selected herbicides and plant hormones on Prototheca wickerhamii. Prototheca wickerhamii was treated in vitro with 11 different herbicides and plant hormones. Growth was inhibited by indolyl-3-acetic acid, indolyl-3-butyric acid and indolyl-3-propionic acid at 400 mug per ml. Coconut milk was stimulatory."} {"id": "PMID:1263246", "title": "Growth, survival, antigenic stability, and virulence of Leptospira interrogans serotype canicola.", "content": "Leptospira interrogans serotype canicola (strain NADL A-13) grew from inocula as small as two cells in liquid polysorbate 80 medium (P-80 medium, in P-60, P-40 and P-20 media, and in P-80 medium from which polysorbate, NH4C1 or thiamine had been omitted. It grew well initially in vitamin B12-deleted P-80 medium, but only with inocula as large as 26 x 10(4) cells per ml. P-80 medium lacking both polysorbate and NH4Cl supported light growth from small inocula, but the omission of thiamine and vitamin B12 in addition seriously affected the properties of the medium. Where readily detectable growth did not develop in liquid nutrient-deleted medium, viable ortanisms could often be demonstrated indirectly by subculture to semisolid medium, and their occurrence was influenced by the presence of albumin, thiamine, and vitamin B12. Growth on semisolid media was comparable with that in liquid media of similar composition. The absence of polysorbate 80, thiamine, or vitamin B12 prevented the appearance of Dinger's zones of growth from small inocula. Antigenic composition as measured by microscopic agglutination tests with homologous and heterologous antisera was not appreciably affected by repeated subculturing in various complete and incomplete media. Homogenates of infected-hamster-kidney tissue in bovine serum-albumin diluent still contained viable organisms after 60 days' storage at 23-25 degrees C. Organisms derived from this material after 3 and 16 days' storage showed no loss of virulence. Organisms grown in artificial culture showed no loss of virulence after storage in bovine albumin diluent or phosphate buffer for 7 days at 23-25 degrees C. Cultures of the organism survived without loss of virulence for 15 months in 13 semisolid media of differing complexity. Single colonies derived from five different solid media were grown in semisolid forms of the parent media and stored at 23-25 degrees C for 10 months without loss of virulence.", "contents": "Growth, survival, antigenic stability, and virulence of Leptospira interrogans serotype canicola. Leptospira interrogans serotype canicola (strain NADL A-13) grew from inocula as small as two cells in liquid polysorbate 80 medium (P-80 medium, in P-60, P-40 and P-20 media, and in P-80 medium from which polysorbate, NH4C1 or thiamine had been omitted. It grew well initially in vitamin B12-deleted P-80 medium, but only with inocula as large as 26 x 10(4) cells per ml. P-80 medium lacking both polysorbate and NH4Cl supported light growth from small inocula, but the omission of thiamine and vitamin B12 in addition seriously affected the properties of the medium. Where readily detectable growth did not develop in liquid nutrient-deleted medium, viable ortanisms could often be demonstrated indirectly by subculture to semisolid medium, and their occurrence was influenced by the presence of albumin, thiamine, and vitamin B12. Growth on semisolid media was comparable with that in liquid media of similar composition. The absence of polysorbate 80, thiamine, or vitamin B12 prevented the appearance of Dinger's zones of growth from small inocula. Antigenic composition as measured by microscopic agglutination tests with homologous and heterologous antisera was not appreciably affected by repeated subculturing in various complete and incomplete media. Homogenates of infected-hamster-kidney tissue in bovine serum-albumin diluent still contained viable organisms after 60 days' storage at 23-25 degrees C. Organisms derived from this material after 3 and 16 days' storage showed no loss of virulence. Organisms grown in artificial culture showed no loss of virulence after storage in bovine albumin diluent or phosphate buffer for 7 days at 23-25 degrees C. Cultures of the organism survived without loss of virulence for 15 months in 13 semisolid media of differing complexity. Single colonies derived from five different solid media were grown in semisolid forms of the parent media and stored at 23-25 degrees C for 10 months without loss of virulence."} {"id": "PMID:1263247", "title": "The comparison and characterisation of glycolytic mycoplasmas isolated from the respiratory tract of sheep.", "content": "Nine strains of glycolytic mycoplasmas isolated from the respiratory tract of apparently healthy sheep, pneumonic sheep and sheep with pulmonary adenomatosis (SPA) were compared with a Queensland strain (Y98) of Mycoplasma ovipneumoniae. All strains were very similar in their reactions in 14 biochemical tests and in their sensitivities to optochin, digitonin, sodium polyanethol sulphonate, and 11 antibiotics. Polyacrylamide-gel electrophoresis and serological cross-reactions by the agar-gel double diffusion, metabolic inhibition (MI) and growht-inhibition (GI) tests also showed that all strains could be classified as M. ovipneumoniae. The MI and GI tests, however, showed considerable intraspecific differences among strains, with apparent polarisation of SPA strains and non-SPA strains at opposite ends of the antigenic spectrum. Two representative strains were tested by the MI test against antisera to 39 mycoplasma species or serogroups, with negative results.", "contents": "The comparison and characterisation of glycolytic mycoplasmas isolated from the respiratory tract of sheep. Nine strains of glycolytic mycoplasmas isolated from the respiratory tract of apparently healthy sheep, pneumonic sheep and sheep with pulmonary adenomatosis (SPA) were compared with a Queensland strain (Y98) of Mycoplasma ovipneumoniae. All strains were very similar in their reactions in 14 biochemical tests and in their sensitivities to optochin, digitonin, sodium polyanethol sulphonate, and 11 antibiotics. Polyacrylamide-gel electrophoresis and serological cross-reactions by the agar-gel double diffusion, metabolic inhibition (MI) and growht-inhibition (GI) tests also showed that all strains could be classified as M. ovipneumoniae. The MI and GI tests, however, showed considerable intraspecific differences among strains, with apparent polarisation of SPA strains and non-SPA strains at opposite ends of the antigenic spectrum. Two representative strains were tested by the MI test against antisera to 39 mycoplasma species or serogroups, with negative results."} {"id": "PMID:1263248", "title": "Quantitative studies on the dispersal of skin bacteria into the air.", "content": "Dispersal of skin micro-organisms into the air during undressing was studied in 72 members of surgical and nursing staff. Few pathogens were found to be dispersed. Males dispersed more normal skin organisms than did females. Males were also more heavily colonised than females, and sex differences in dispersal diminished when allowance was made for the denser colonisation of males. Dispersal was correlated most strongly with the counts on the thighs and abdomen in males but on the shins in females.", "contents": "Quantitative studies on the dispersal of skin bacteria into the air. Dispersal of skin micro-organisms into the air during undressing was studied in 72 members of surgical and nursing staff. Few pathogens were found to be dispersed. Males dispersed more normal skin organisms than did females. Males were also more heavily colonised than females, and sex differences in dispersal diminished when allowance was made for the denser colonisation of males. Dispersal was correlated most strongly with the counts on the thighs and abdomen in males but on the shins in females."} {"id": "PMID:1263249", "title": "Clostridia isolated from faeces.", "content": "Clostridia were isolated from human faecal samples from England, Scotland, Wales, USA, Hong Kong, Uganda and Japan. Strains were identified on the basis of various biochemical reactions and on the type of fatty acid produced from glucose. Analysis of these acids was by gas-liquid chromatography. Clostridium paraputrificum was common in stool samples from England, Scotland, Wales, and USA, but rare in samples from Hong Kong, Uganda and Japan.", "contents": "Clostridia isolated from faeces. Clostridia were isolated from human faecal samples from England, Scotland, Wales, USA, Hong Kong, Uganda and Japan. Strains were identified on the basis of various biochemical reactions and on the type of fatty acid produced from glucose. Analysis of these acids was by gas-liquid chromatography. Clostridium paraputrificum was common in stool samples from England, Scotland, Wales, and USA, but rare in samples from Hong Kong, Uganda and Japan."} {"id": "PMID:1263250", "title": "Isolation of the major intrinsic transmembrane protein of the human erythrocyte membrane.", "content": "The major intrinsic protein of the human erythrocyte membrane commonly referred to as \"Band 3\", was isolated by a multi-step procedure. Extraction of ghost membranes in dilute solutions of lithium diiodosalicylate removed most of the proteins considered to be extrinsic to the membrane. The resulting membrane fragments were solubilized in sodium dodecyl sulfate, and the major sialoglycoprotein (glycophorin A) was removed by wheat germ agglutinin-Sepharose affinity chromatography. Gel filtration in sodium dodecyl sulfate was used as the final step to yield the band 3 polypeptide in electrophoretically homogeneous form.", "contents": "Isolation of the major intrinsic transmembrane protein of the human erythrocyte membrane. The major intrinsic protein of the human erythrocyte membrane commonly referred to as \"Band 3\", was isolated by a multi-step procedure. Extraction of ghost membranes in dilute solutions of lithium diiodosalicylate removed most of the proteins considered to be extrinsic to the membrane. The resulting membrane fragments were solubilized in sodium dodecyl sulfate, and the major sialoglycoprotein (glycophorin A) was removed by wheat germ agglutinin-Sepharose affinity chromatography. Gel filtration in sodium dodecyl sulfate was used as the final step to yield the band 3 polypeptide in electrophoretically homogeneous form."} {"id": "PMID:1263251", "title": "Cell size and mutual cell adhesion. I. Increase in mutual adhesivenes of HeLa cells from density-inhibited suspension cultures by hypotonic treatment.", "content": "HeLa cells harvested from density-inhibited or fast growing suspension cultures, were incubated in NaCl solutions of different tonicity. Cell size enlargement produced by hypotonicity is accompanied by an increased sedimentation rate of the density-inhibited cells, whereas no appreciable change is observed in the sedimentation rate of fast growing cells. Hypotonicity also has no effect on the sedimentation rate of density-inhibited cells which previously had been treated with neuraminidase or trypsin. It is shown that the effect of hypotonicity on density-inhibited cells cannot be ascribed to release of cell surface sialic acids during hypotonic incubation. Several arguments are presented which indicate that the changes in sedimentation rate, as measured in the rotating suspension system, are not the direct consequence of the alterations in cell size, but rather must be attributed to differences in intercellular adhesiveness resulting from the size alterations. Analogous changes in intercellular adhesiveness and cell size are shown to occur during growth in isotonic suspension culture. The results can be explained by assuming that changes in cell size affect the intercellular adhesiveness by modifying the extent to which cell surface sialic acids counteract adhesion.", "contents": "Cell size and mutual cell adhesion. I. Increase in mutual adhesivenes of HeLa cells from density-inhibited suspension cultures by hypotonic treatment. HeLa cells harvested from density-inhibited or fast growing suspension cultures, were incubated in NaCl solutions of different tonicity. Cell size enlargement produced by hypotonicity is accompanied by an increased sedimentation rate of the density-inhibited cells, whereas no appreciable change is observed in the sedimentation rate of fast growing cells. Hypotonicity also has no effect on the sedimentation rate of density-inhibited cells which previously had been treated with neuraminidase or trypsin. It is shown that the effect of hypotonicity on density-inhibited cells cannot be ascribed to release of cell surface sialic acids during hypotonic incubation. Several arguments are presented which indicate that the changes in sedimentation rate, as measured in the rotating suspension system, are not the direct consequence of the alterations in cell size, but rather must be attributed to differences in intercellular adhesiveness resulting from the size alterations. Analogous changes in intercellular adhesiveness and cell size are shown to occur during growth in isotonic suspension culture. The results can be explained by assuming that changes in cell size affect the intercellular adhesiveness by modifying the extent to which cell surface sialic acids counteract adhesion."} {"id": "PMID:1263252", "title": "Cell size and mutual cell adhesion. II. Evidence for a relation between cell size, long-range electrostatic repulsion and intercellular adhesiveness during density-regulated growth in suspension.", "content": "The strength of the long-range electrostatic repulsion forces on HeLa cells is measured by agglutinative titration using low molecular weight polylysine (M.W. 11,000). Repulsion forces, found to be present on the smaller HeLa cells from density-inhibited suspension cultures, are weakened by incubation of the cells in hypotonic NaCl solutions. Repulsion forces, found to be absent on the larger cells from fast growing cultures, can be induced on these cells by incubation in hypertonic NaCl solutions. Both effects of anisotonicity are reversible, and disappear on restoration of the medium to normal tonicity. Induction of repulsion forces on fast growing cells is prevented by previous treatment of the cells with neuraminidase. Neuraminidase also abolishes repulsion on density-inhibited cells. It is proposed that alterations of the cell size, produced by anisotonicity or occurring during growth in isotonic suspension medium, affect mutual cell adhesiveness by modifying the strength of the repulsion forces generated by cell surface sialic acids.", "contents": "Cell size and mutual cell adhesion. II. Evidence for a relation between cell size, long-range electrostatic repulsion and intercellular adhesiveness during density-regulated growth in suspension. The strength of the long-range electrostatic repulsion forces on HeLa cells is measured by agglutinative titration using low molecular weight polylysine (M.W. 11,000). Repulsion forces, found to be present on the smaller HeLa cells from density-inhibited suspension cultures, are weakened by incubation of the cells in hypotonic NaCl solutions. Repulsion forces, found to be absent on the larger cells from fast growing cultures, can be induced on these cells by incubation in hypertonic NaCl solutions. Both effects of anisotonicity are reversible, and disappear on restoration of the medium to normal tonicity. Induction of repulsion forces on fast growing cells is prevented by previous treatment of the cells with neuraminidase. Neuraminidase also abolishes repulsion on density-inhibited cells. It is proposed that alterations of the cell size, produced by anisotonicity or occurring during growth in isotonic suspension medium, affect mutual cell adhesiveness by modifying the strength of the repulsion forces generated by cell surface sialic acids."} {"id": "PMID:1263253", "title": "Reflection coefficients of permeant nonelectrolytes for dog and beef red cell membranes.", "content": "The reflection coefficient, sigma, for several small permeant nonelectrolytes was determined for dog and beef red blood cell membranes. Our sigma values were considerably higher than those previously reported for dog cells; e.g., out sigma urea was 87% higher than the sigma urea of Rich, Sha'afi, Barton and Solomon (J. Gen. Physiol. 50: 2391, 1967). Our sigma values for urea were only slightly greater in beef cells than previously reported by Farmer and Macey (Biochim. Biophys. Acta 290: 290, 1972). We found that a trend exists when (1 - sigma) is plotted against the log of the permeability coefficient, omega. This observation is also consistent with our previously reported sigma data for human red cell membranes (Owen & Eyring, J. Gen. Physiol. 66: 241, 1972). This trend suggests that small hydrophilic molecules interact highly with cell membrane water. The exceptions to this trend were lipophilic molecules, indicating they do not interact with water while penetrating the red cell membrane.", "contents": "Reflection coefficients of permeant nonelectrolytes for dog and beef red cell membranes. The reflection coefficient, sigma, for several small permeant nonelectrolytes was determined for dog and beef red blood cell membranes. Our sigma values were considerably higher than those previously reported for dog cells; e.g., out sigma urea was 87% higher than the sigma urea of Rich, Sha'afi, Barton and Solomon (J. Gen. Physiol. 50: 2391, 1967). Our sigma values for urea were only slightly greater in beef cells than previously reported by Farmer and Macey (Biochim. Biophys. Acta 290: 290, 1972). We found that a trend exists when (1 - sigma) is plotted against the log of the permeability coefficient, omega. This observation is also consistent with our previously reported sigma data for human red cell membranes (Owen & Eyring, J. Gen. Physiol. 66: 241, 1972). This trend suggests that small hydrophilic molecules interact highly with cell membrane water. The exceptions to this trend were lipophilic molecules, indicating they do not interact with water while penetrating the red cell membrane."} {"id": "PMID:1263263", "title": "Coenzymes as fossils of an earlier metabolic state.", "content": "A metabolic system composed of nucleic acid enzymes is proposed to have existed prior to the evolution of ribosomal protein synthesis. Vestiges of these nucleic acid enzymes persist in contemporary coenzymes. This proposal rationalizes the fact that many coenzymes are nucleotides or heterocyclic bases which could be derived from nucleotides.", "contents": "Coenzymes as fossils of an earlier metabolic state. A metabolic system composed of nucleic acid enzymes is proposed to have existed prior to the evolution of ribosomal protein synthesis. Vestiges of these nucleic acid enzymes persist in contemporary coenzymes. This proposal rationalizes the fact that many coenzymes are nucleotides or heterocyclic bases which could be derived from nucleotides."} {"id": "PMID:1263264", "title": "Structural characterization of thermal prebiotic polypeptides.", "content": "Thermal polycondensation of amino-acids as a possible prebiotic path of chemical evolution of life has been critically examined. The polymeric materials studied by nmr methods have scarce resemblance to natural peptidic material because beta, gamma and eplision peptide bonds largely predominate over a-peptide bonds.", "contents": "Structural characterization of thermal prebiotic polypeptides. Thermal polycondensation of amino-acids as a possible prebiotic path of chemical evolution of life has been critically examined. The polymeric materials studied by nmr methods have scarce resemblance to natural peptidic material because beta, gamma and eplision peptide bonds largely predominate over a-peptide bonds."} {"id": "PMID:1263265", "title": "Conservation of repeated DNA base sequences in Crustacea: a molecular approach to decapod phylogeny.", "content": "Analysis of data obtained from molecular hybridization of 3H-labeled repetitious DNA has been utilized to reconstruct the broad outlines of phylogenetic relationships among decapod Crustacea. This molecular reconstruction agrees reasonably well with the paleontological record, and with other schemes obtained by comparative morphological and serological approaches. Preliminary evidence is in line with the hypothesis that continuous addition of new repeated sequence families to the genome over long periods of time may in part account for the correlation observed between percent repetitious DNA hybridized and divergence time. It is tentatively concluded that a core of DNA base sequence homology has been highly conserved throughout the evolution of the Crustacea. Demonstration of inter-species sequence homology has important implications to models which relegate a genetic regulatory function to repeated DNAs.", "contents": "Conservation of repeated DNA base sequences in Crustacea: a molecular approach to decapod phylogeny. Analysis of data obtained from molecular hybridization of 3H-labeled repetitious DNA has been utilized to reconstruct the broad outlines of phylogenetic relationships among decapod Crustacea. This molecular reconstruction agrees reasonably well with the paleontological record, and with other schemes obtained by comparative morphological and serological approaches. Preliminary evidence is in line with the hypothesis that continuous addition of new repeated sequence families to the genome over long periods of time may in part account for the correlation observed between percent repetitious DNA hybridized and divergence time. It is tentatively concluded that a core of DNA base sequence homology has been highly conserved throughout the evolution of the Crustacea. Demonstration of inter-species sequence homology has important implications to models which relegate a genetic regulatory function to repeated DNAs."} {"id": "PMID:1263279", "title": "Studies on the biological disposition of diethylstilbestrol in rats and humans.", "content": "Studies were conducted to elucidate the processes involved in the biological disposition of diethylstilbestrol (DES). The apparent biological half-life of [14C] DES decreased with increasing age in immature rats. The half-life of DES in adult rats (14 min) was reached between the 15th and 25th day after birth. Comparison of the intestinal absorption of [14C] DES and [14C]DES monoglucuronide showed the unconjugated drug to be absorbed much more rapidly. Hydrolysis of the conjugate took place in the lower intestine, and this permitted the drug to undergo enterohepatic cycling.", "contents": "Studies on the biological disposition of diethylstilbestrol in rats and humans. Studies were conducted to elucidate the processes involved in the biological disposition of diethylstilbestrol (DES). The apparent biological half-life of [14C] DES decreased with increasing age in immature rats. The half-life of DES in adult rats (14 min) was reached between the 15th and 25th day after birth. Comparison of the intestinal absorption of [14C] DES and [14C]DES monoglucuronide showed the unconjugated drug to be absorbed much more rapidly. Hydrolysis of the conjugate took place in the lower intestine, and this permitted the drug to undergo enterohepatic cycling."} {"id": "PMID:1263280", "title": "Isolation and identification of metabolites of 14C-labeled estradiol in cattle.", "content": "A total of six steers and six heifers received three daily injections containing either 200 muCi (1 mg) of [4-14C] estradiol-17beta or 312 muCi (2.16 mg) of [4-14C] estradiol 17beta 3-benzoate. Major metabolites of the administered estradiol-17beta and estradiol-17beta 3-benzoate were identified in muscle, fat, liver, and kidney samples obtained 3 hr after the final injection. Estradiol benzoate was nondetectable in the tissues analyzed, suggesting rapid hydrolysis of the benzoate ester. Consequently, the relative proportions of the various metabolites were similar for both the injected estrogens. Estradiol-17beta and estrone, which together accounted for 80-90% of the total extracted radioactivity, appear to be the major metabolites in both muscle and fats. In contrast, the major metabolites present in liver and kidney appear in the conjugate fraction. Most of the conjugated metabolites were glucuronates, which represent 85-95% of the total recovered conjugate radioactivity.", "contents": "Isolation and identification of metabolites of 14C-labeled estradiol in cattle. A total of six steers and six heifers received three daily injections containing either 200 muCi (1 mg) of [4-14C] estradiol-17beta or 312 muCi (2.16 mg) of [4-14C] estradiol 17beta 3-benzoate. Major metabolites of the administered estradiol-17beta and estradiol-17beta 3-benzoate were identified in muscle, fat, liver, and kidney samples obtained 3 hr after the final injection. Estradiol benzoate was nondetectable in the tissues analyzed, suggesting rapid hydrolysis of the benzoate ester. Consequently, the relative proportions of the various metabolites were similar for both the injected estrogens. Estradiol-17beta and estrone, which together accounted for 80-90% of the total extracted radioactivity, appear to be the major metabolites in both muscle and fats. In contrast, the major metabolites present in liver and kidney appear in the conjugate fraction. Most of the conjugated metabolites were glucuronates, which represent 85-95% of the total recovered conjugate radioactivity."} {"id": "PMID:1263281", "title": "Estrogen concentrations in bovine and porcine tissues.", "content": "Using an estrogen antiserum that measures biologically active estrogen (estradiol-17beta + estrone), a series of studies have been completed to describe the normal plasma levels of estrogen in cows and sows during various stages of reproduction. The levels are lower in the nonpregnant cow (less than 25 pg/ml) than in most species. Only during late pregnancy are the levels easily assayed. The levels in the nonpregnant sow are 2-3 times greater than in the cow. In both species there is a preovulatory peak of estrogen that is responsible for estrus. Plasma estrogen concentrations were also determined after induction of multiple ovulations by exogenous gonadotropin (PMSG) in the cow and sow and after treatment of cows with either a progestin (MGA) or a prostaglandin (PGF2alpha). (These two drugs have been used to synchronize estrus in the cow.) Estrogen levels rise greatly after treatment with PMSG but show little effect from MGA or PGF2alpha. Data are also presented on the validation of an assay for E2beta and E1 in beef tissue. Less than 20 pg of E2beta and E1 was measured per gram bovine muscle tissue. Considerable effort must be expended to apply radioimmunoassay to the assay of estrogens in tissues.", "contents": "Estrogen concentrations in bovine and porcine tissues. Using an estrogen antiserum that measures biologically active estrogen (estradiol-17beta + estrone), a series of studies have been completed to describe the normal plasma levels of estrogen in cows and sows during various stages of reproduction. The levels are lower in the nonpregnant cow (less than 25 pg/ml) than in most species. Only during late pregnancy are the levels easily assayed. The levels in the nonpregnant sow are 2-3 times greater than in the cow. In both species there is a preovulatory peak of estrogen that is responsible for estrus. Plasma estrogen concentrations were also determined after induction of multiple ovulations by exogenous gonadotropin (PMSG) in the cow and sow and after treatment of cows with either a progestin (MGA) or a prostaglandin (PGF2alpha). (These two drugs have been used to synchronize estrus in the cow.) Estrogen levels rise greatly after treatment with PMSG but show little effect from MGA or PGF2alpha. Data are also presented on the validation of an assay for E2beta and E1 in beef tissue. Less than 20 pg of E2beta and E1 was measured per gram bovine muscle tissue. Considerable effort must be expended to apply radioimmunoassay to the assay of estrogens in tissues."} {"id": "PMID:1263282", "title": "Studies on metabolism and effects of estrogen on pituitary prolactin and LH secretion.", "content": "The effect of a subcutaneous injection of estradiol on the secretion of pituitary prolactin in the rat and the relationship between serum estradiol level and luteinizing hormone (LH) secretion in mare were reviewed. In addition, the effect of estradiol injection on LH secretion and the metabolism of [14C] estradiol in intact and bile duct fistulated pony mares were studied. Low (0.1 mug/day/rat) to moderate dose (5 mug/day/rat) of estradiol benzoate injected subcutaneously to mature or immature rats significantly increased pituitary content of prolactin and serum prolactin level five- to tenfold. On the other hand, high dose of estradiol (10 mug/day/rat or more) was less effective in stimulating prolactin secretion, and it appeared that progesterone injected concurrently with estradiol had some inhibitory action on the stimulatory effect of estradiol. Studies in pony mares showed that the physiologic level of serum estradiol during proestrus was important for the induction of the ovulatory surge of LH. Intramuscular injection of a low dose (2 or 4 mg/mare) of estradiol was stimulatory, whereas a high dose (8 mg/mare) was inhibitory for LH secretion in pony mares. Results of the estradiol metabolism studies indicated a relatively long half-life for estradiol in the mare. The majority of the [14C] estradiol metabolites appeared in the urine within 24 hr following intravenous injection. Enterohepatic circulation appeared to be important for estradiol metabolism in mare.", "contents": "Studies on metabolism and effects of estrogen on pituitary prolactin and LH secretion. The effect of a subcutaneous injection of estradiol on the secretion of pituitary prolactin in the rat and the relationship between serum estradiol level and luteinizing hormone (LH) secretion in mare were reviewed. In addition, the effect of estradiol injection on LH secretion and the metabolism of [14C] estradiol in intact and bile duct fistulated pony mares were studied. Low (0.1 mug/day/rat) to moderate dose (5 mug/day/rat) of estradiol benzoate injected subcutaneously to mature or immature rats significantly increased pituitary content of prolactin and serum prolactin level five- to tenfold. On the other hand, high dose of estradiol (10 mug/day/rat or more) was less effective in stimulating prolactin secretion, and it appeared that progesterone injected concurrently with estradiol had some inhibitory action on the stimulatory effect of estradiol. Studies in pony mares showed that the physiologic level of serum estradiol during proestrus was important for the induction of the ovulatory surge of LH. Intramuscular injection of a low dose (2 or 4 mg/mare) of estradiol was stimulatory, whereas a high dose (8 mg/mare) was inhibitory for LH secretion in pony mares. Results of the estradiol metabolism studies indicated a relatively long half-life for estradiol in the mare. The majority of the [14C] estradiol metabolites appeared in the urine within 24 hr following intravenous injection. Enterohepatic circulation appeared to be important for estradiol metabolism in mare."} {"id": "PMID:1263283", "title": "Reproductive endocrinology of female chimpanzees: a suitable model of humans.", "content": "Similarities between reproductive processes in humans and chimpanzees have led to speculation that the chimpanzee might be an excellent reproductive-endocrine model of humans. Data comparing patterns and concentrations of serum gonadotropins, prolactin, and sex steroids in female humans, chimpanzees, and rhesus monkeys sustain this concept. The striking evidence that levels of estrone, estradiol, estriol, progesterone, and chorionic gonadotropin are similar during human and chimpanzee pregnancy support the contention that chimpanzees, like humans but unlike rhesus monkeys, have a definitive fetoplacental unit. Likewise, during normal menstrual cycles serum patterns of LH, FSH, progesterone, and estradiol are similar in women and chimpanzees, but differ in rhesus monkeys. Thus by using the chimpanzee it may be possible to accurately assess the safety for human use of compounds that might affect reproductive-endocrine processes without direct exposure to humans.", "contents": "Reproductive endocrinology of female chimpanzees: a suitable model of humans. Similarities between reproductive processes in humans and chimpanzees have led to speculation that the chimpanzee might be an excellent reproductive-endocrine model of humans. Data comparing patterns and concentrations of serum gonadotropins, prolactin, and sex steroids in female humans, chimpanzees, and rhesus monkeys sustain this concept. The striking evidence that levels of estrone, estradiol, estriol, progesterone, and chorionic gonadotropin are similar during human and chimpanzee pregnancy support the contention that chimpanzees, like humans but unlike rhesus monkeys, have a definitive fetoplacental unit. Likewise, during normal menstrual cycles serum patterns of LH, FSH, progesterone, and estradiol are similar in women and chimpanzees, but differ in rhesus monkeys. Thus by using the chimpanzee it may be possible to accurately assess the safety for human use of compounds that might affect reproductive-endocrine processes without direct exposure to humans."} {"id": "PMID:1263286", "title": "The superior gluteal: an artery at risk in blunt pelvic trauma.", "content": "Five patients with pelvic fractures were studied arteriographically and all were found to have injury to one or both superior gluteal arteries, in addition to other injuries. In three of the five patients no adjacent bony damage was seen on plain pelvic roentgenograms. A possible explanation for this finding is given in terms of anatomic relationships within the pelvis. The importance of early arteriography in the diagnosis management of blunt pelvic trauma is emphasized.", "contents": "The superior gluteal: an artery at risk in blunt pelvic trauma. Five patients with pelvic fractures were studied arteriographically and all were found to have injury to one or both superior gluteal arteries, in addition to other injuries. In three of the five patients no adjacent bony damage was seen on plain pelvic roentgenograms. A possible explanation for this finding is given in terms of anatomic relationships within the pelvis. The importance of early arteriography in the diagnosis management of blunt pelvic trauma is emphasized."} {"id": "PMID:1263287", "title": "The effect of hypertonic glucose upon survival in hemorrhagic shock utilizing a re-stress model in sheep.", "content": "Twenty-three adult sheep were subjected to hemorrhagic shock using a re-stress model. Eleven of the animals served as controls and were resuscitated with shed blood and crystaloid. The remaining twelve were resuscitated in the same manner with the addition of hypertonic glucose. There was a highly significant increase in survival of the animals given hypertonic glucose.", "contents": "The effect of hypertonic glucose upon survival in hemorrhagic shock utilizing a re-stress model in sheep. Twenty-three adult sheep were subjected to hemorrhagic shock using a re-stress model. Eleven of the animals served as controls and were resuscitated with shed blood and crystaloid. The remaining twelve were resuscitated in the same manner with the addition of hypertonic glucose. There was a highly significant increase in survival of the animals given hypertonic glucose."} {"id": "PMID:1263288", "title": "Role of protein binding of cytotoxic anions in post-traumatic pulmonary insufficiency.", "content": "Anions of fatty acids infused intravenously into dogs clearly duplicate the clinical syndrome of post-traumatic pulmonary insufficiency (congestive atelectasis, shock lung, traumatic wet lung). Neutral fat embolized to the lungs is incapable of producing this syndrome within the time investigated. The incubation of fatty acid anions with human serum albumin before injection obviates the severe desaturation of blood and ultrastructure disruption caused by FAA alone.", "contents": "Role of protein binding of cytotoxic anions in post-traumatic pulmonary insufficiency. Anions of fatty acids infused intravenously into dogs clearly duplicate the clinical syndrome of post-traumatic pulmonary insufficiency (congestive atelectasis, shock lung, traumatic wet lung). Neutral fat embolized to the lungs is incapable of producing this syndrome within the time investigated. The incubation of fatty acid anions with human serum albumin before injection obviates the severe desaturation of blood and ultrastructure disruption caused by FAA alone."} {"id": "PMID:1263292", "title": "The value of ethambutol in the treatment of tuberculous meningitis.", "content": "This is a prospective treatment study of 86 patients with tuberculous meningitis admitted to the Abbassia Fever Hospital Cairo, Egypt. The causative organism was cultured from the cerebro spinal fluidin 47 patients, was identified by Zeihl Nelson stain in five and in the remaining 34 patients the diagnosis was based on the clinical course and changes in the CSF chemistry and cell count. The data indicate that ethambutol can be used as a companion drug to INH and streptomycin in the treatment of the disease and that the mortality is directly dependent on the state of consciousness upon initiation of therapy.", "contents": "The value of ethambutol in the treatment of tuberculous meningitis. This is a prospective treatment study of 86 patients with tuberculous meningitis admitted to the Abbassia Fever Hospital Cairo, Egypt. The causative organism was cultured from the cerebro spinal fluidin 47 patients, was identified by Zeihl Nelson stain in five and in the remaining 34 patients the diagnosis was based on the clinical course and changes in the CSF chemistry and cell count. The data indicate that ethambutol can be used as a companion drug to INH and streptomycin in the treatment of the disease and that the mortality is directly dependent on the state of consciousness upon initiation of therapy."} {"id": "PMID:1263294", "title": "Leishmaniasis in Brazil: XI. Observations on the morphology of Leishmania of the brazilensis and mexicana complexes.", "content": "The present work shows that the amastigotes of L. m. amazonensis are morphologically distinguishable from those of L. b braziliensis. The authors consider that such differences add further support to the use of the name braziliensis and mexicana at the specific level.", "contents": "Leishmaniasis in Brazil: XI. Observations on the morphology of Leishmania of the brazilensis and mexicana complexes. The present work shows that the amastigotes of L. m. amazonensis are morphologically distinguishable from those of L. b braziliensis. The authors consider that such differences add further support to the use of the name braziliensis and mexicana at the specific level."} {"id": "PMID:1263295", "title": "An evaluation of factors relevant to the diagnosis of bronchial carcinoma in Sri Lanka.", "content": "The incidence of bronchial carcinoma in Sri Lanka is low. The extent to which its pattern varies from that prevailing in western countries is demonstrated by a study of 84 cases diagnosed over a 10-year period. Of the patients examined 45-2 per cent were non-smokers, all 17 women belonging to this category. A negative smoking history, especially in women, was not a useful guide in assessing a suspected lesion. Adenocarcinoma, which is usually peripheral, comprised a high proportion of the tumours (22-6%). The majority of cases (70-3%) had had peripheral tumours which were beyond bronchoscopic visibility. Therefore, bronchoscopy was not as useful a diagnostic procedure as in the West. Digital clubbing was seen in less than half the males, while only two females had this sign.", "contents": "An evaluation of factors relevant to the diagnosis of bronchial carcinoma in Sri Lanka. The incidence of bronchial carcinoma in Sri Lanka is low. The extent to which its pattern varies from that prevailing in western countries is demonstrated by a study of 84 cases diagnosed over a 10-year period. Of the patients examined 45-2 per cent were non-smokers, all 17 women belonging to this category. A negative smoking history, especially in women, was not a useful guide in assessing a suspected lesion. Adenocarcinoma, which is usually peripheral, comprised a high proportion of the tumours (22-6%). The majority of cases (70-3%) had had peripheral tumours which were beyond bronchoscopic visibility. Therefore, bronchoscopy was not as useful a diagnostic procedure as in the West. Digital clubbing was seen in less than half the males, while only two females had this sign."} {"id": "PMID:1263297", "title": "Toxoplasma infection of stray cats in Egypt.", "content": "A seroepidemiological survey of cats for Toxoplasma antibody revealed a high infection rate. No significant difference was detected between males and females or between rural and urban areas, although acute infection seems to be more prevalent in males and in rural areas as revealed by the high titres of the dye test. Toxoplasmosis in cats, as revealed by serologic surveys, seems to prevail more during the warm rather than the hot season of the year being favoured by milder temperature and higher relative humidity and rainfall in the former season. Futhermore, it was concluded that infection rate with Toxoplasma increases with the age of the host. Toxoplasma antibody in the young age groups is to a great extent of maternal origin. Study of the relationship of Toxoplasma to Isospora showed no cross immunity. They follow a reversed pattern with increasing age of the host. Data also shows the high specificity of dye testing for detection of Toxoplasma antibody. Feeding experiments show that a relatively high percentage of cats shed oocysts in their faeces. Not only seropositive but also seronegative cats excrete oocysts, though at a lower rate in the latter case. The majority of cats shedding oocysts are those with either low positive titres or seronegative cats.", "contents": "Toxoplasma infection of stray cats in Egypt. A seroepidemiological survey of cats for Toxoplasma antibody revealed a high infection rate. No significant difference was detected between males and females or between rural and urban areas, although acute infection seems to be more prevalent in males and in rural areas as revealed by the high titres of the dye test. Toxoplasmosis in cats, as revealed by serologic surveys, seems to prevail more during the warm rather than the hot season of the year being favoured by milder temperature and higher relative humidity and rainfall in the former season. Futhermore, it was concluded that infection rate with Toxoplasma increases with the age of the host. Toxoplasma antibody in the young age groups is to a great extent of maternal origin. Study of the relationship of Toxoplasma to Isospora showed no cross immunity. They follow a reversed pattern with increasing age of the host. Data also shows the high specificity of dye testing for detection of Toxoplasma antibody. Feeding experiments show that a relatively high percentage of cats shed oocysts in their faeces. Not only seropositive but also seronegative cats excrete oocysts, though at a lower rate in the latter case. The majority of cats shedding oocysts are those with either low positive titres or seronegative cats."} {"id": "PMID:1263306", "title": "Massive renal hemorrhage associated with parturition.", "content": "Spontaneous massive renal hemorrhage, during or after parturition, not associated with blood dyscrasias or other recognizable etiology is rare. Two new cases are added to the 7 cases previously reported. The related literature is reviewed.", "contents": "Massive renal hemorrhage associated with parturition. Spontaneous massive renal hemorrhage, during or after parturition, not associated with blood dyscrasias or other recognizable etiology is rare. Two new cases are added to the 7 cases previously reported. The related literature is reviewed."} {"id": "PMID:1263307", "title": "Renovascular hypertension: does the renal vein renin ratio predict operative results?", "content": "Renal vein renin ratios from 56 hypertensive patients who were operated upon for unilateral stenosis of a main renal artery were compared to blood pressure response to a corrective operation. In patients with renal vein renin ratios greater then 2.0, the upper limits of normal for essential hypertension (95 per cent confidence limits), the cure/improvement rate approximated 90 per cent. However, in patients operated upon despite lesser ratios the cure/improvement rate was also high--83 per cent in our series and 57 per cent in collected reports from the literature. Thus, the test may be falsely negative in a high percentage of patients. Renal vein renin ratios would appear to be most useful in confirming but not necessarily in denying the functional significance of a renal artery stenosis.", "contents": "Renovascular hypertension: does the renal vein renin ratio predict operative results? Renal vein renin ratios from 56 hypertensive patients who were operated upon for unilateral stenosis of a main renal artery were compared to blood pressure response to a corrective operation. In patients with renal vein renin ratios greater then 2.0, the upper limits of normal for essential hypertension (95 per cent confidence limits), the cure/improvement rate approximated 90 per cent. However, in patients operated upon despite lesser ratios the cure/improvement rate was also high--83 per cent in our series and 57 per cent in collected reports from the literature. Thus, the test may be falsely negative in a high percentage of patients. Renal vein renin ratios would appear to be most useful in confirming but not necessarily in denying the functional significance of a renal artery stenosis."} {"id": "PMID:1263308", "title": "Hepatorenal artery bypass in the management of renovascular hypertension.", "content": "Infrequently, when the aorta cannot be used for a standard renal bypass operation because of a previous aortic operation, severe degenerative atherosclerosis or complete aortic thrombosis, a unilateral (hepatic) or bilateral (hepatic and splenic) visceral bypass should be contemplated. Patients with abdominal aortic aneurysms extending above the renal arteries might benefit from concomitant bilateral visceral bypass procedures followed by aortic replacement during the same operative session. The hepatic circulation with its common anatomic variations, indications, surgical technique and effects of hepatorenal artery bypass on the renal and hepatic circulation are discussed.", "contents": "Hepatorenal artery bypass in the management of renovascular hypertension. Infrequently, when the aorta cannot be used for a standard renal bypass operation because of a previous aortic operation, severe degenerative atherosclerosis or complete aortic thrombosis, a unilateral (hepatic) or bilateral (hepatic and splenic) visceral bypass should be contemplated. Patients with abdominal aortic aneurysms extending above the renal arteries might benefit from concomitant bilateral visceral bypass procedures followed by aortic replacement during the same operative session. The hepatic circulation with its common anatomic variations, indications, surgical technique and effects of hepatorenal artery bypass on the renal and hepatic circulation are discussed."} {"id": "PMID:1263309", "title": "Transplantation of human renal cell carcinoma to the nude mice: as an intermediate of in vivo and in vitro studies.", "content": "Five human renal cell carcinomas were transplanted successfully to nude mice fed and grown under a specific pathogen-free condition. The histology of the transplanted tumor tissue was a close reproduction of the original human cancer tissue in situ. The transplanted tumor tissue possessed an abundant supply of blood vessels, which was considered to be of host animal origin. All transplanted tumor cells grew easily when transferred to an in vitro cell culture system from the nude mice. In this latter cell culture system tumor cells demonstrated a growth pattern characteristic of epithelial cells. The electron microscopy of these cells showed some characteristic morphological features that indicated their cytological origin.", "contents": "Transplantation of human renal cell carcinoma to the nude mice: as an intermediate of in vivo and in vitro studies. Five human renal cell carcinomas were transplanted successfully to nude mice fed and grown under a specific pathogen-free condition. The histology of the transplanted tumor tissue was a close reproduction of the original human cancer tissue in situ. The transplanted tumor tissue possessed an abundant supply of blood vessels, which was considered to be of host animal origin. All transplanted tumor cells grew easily when transferred to an in vitro cell culture system from the nude mice. In this latter cell culture system tumor cells demonstrated a growth pattern characteristic of epithelial cells. The electron microscopy of these cells showed some characteristic morphological features that indicated their cytological origin."} {"id": "PMID:1263310", "title": "Bacillus Calmette-Guerin in the treatment of adenocarcinoma of the kidney.", "content": "Of 18 patients with renal adenocarcinoma 10 with metastatic disease received Bacillus Calmette-Guerin immunotherapy. Objective responses were recorded in 4 patients. When the intradermal route and relatively small amounts of vaccine were used the complications were minimal and self-limiting. Bacillus Calmette-Guerin immunotherapy appears to be more effective than other modalities in the treatment of renal adenocarcinoma. However, definitive conclusions cannot be drawn since there is no control group. A prospective clinical trial is now in progress at this institution.", "contents": "Bacillus Calmette-Guerin in the treatment of adenocarcinoma of the kidney. Of 18 patients with renal adenocarcinoma 10 with metastatic disease received Bacillus Calmette-Guerin immunotherapy. Objective responses were recorded in 4 patients. When the intradermal route and relatively small amounts of vaccine were used the complications were minimal and self-limiting. Bacillus Calmette-Guerin immunotherapy appears to be more effective than other modalities in the treatment of renal adenocarcinoma. However, definitive conclusions cannot be drawn since there is no control group. A prospective clinical trial is now in progress at this institution."} {"id": "PMID:1263311", "title": "Anergy and tryptophan metabolism in bladder cancer.", "content": "The tryptophan loading test and cutaneous antigen test were done on 55 patients with various stages of bladder cancer. Patients with an abnormality of tryptophan metabolism showed a greater degree of unreactivity to cutaneous delayed hypersensitivity testing. Of the 23 patients with normal tryptophan metabolism 47 per cent were unreactive to 2 or 3 skin antigens. Of 13 patients with 1 abnormal tryptophan metabolite 62 per cent were unreactive to 2 or 3 skin antigens. Of 19 patients with 2 or more abnormal tryptophan metabolites 68 per cent were unreactive to 2 or 3 antigens.", "contents": "Anergy and tryptophan metabolism in bladder cancer. The tryptophan loading test and cutaneous antigen test were done on 55 patients with various stages of bladder cancer. Patients with an abnormality of tryptophan metabolism showed a greater degree of unreactivity to cutaneous delayed hypersensitivity testing. Of the 23 patients with normal tryptophan metabolism 47 per cent were unreactive to 2 or 3 skin antigens. Of 13 patients with 1 abnormal tryptophan metabolite 62 per cent were unreactive to 2 or 3 skin antigens. Of 19 patients with 2 or more abnormal tryptophan metabolites 68 per cent were unreactive to 2 or 3 antigens."} {"id": "PMID:1263312", "title": "Cysts of the ducts of Cowper's glands.", "content": "We describe 4 patients, 3 of whom were children, with cysts in the ducts of Cowper's glands. Presenting symptoms were testicular pain and urethritis. Voiding urethrography with dilute contrast medium is the best diagnostic aid short or urethroscopy. The cysts were effectively treated by avulsion with a bent wire.", "contents": "Cysts of the ducts of Cowper's glands. We describe 4 patients, 3 of whom were children, with cysts in the ducts of Cowper's glands. Presenting symptoms were testicular pain and urethritis. Voiding urethrography with dilute contrast medium is the best diagnostic aid short or urethroscopy. The cysts were effectively treated by avulsion with a bent wire."} {"id": "PMID:1263313", "title": "Urinary continence after repair of membranous urethral stricture in prostatectomized patients.", "content": "Prostatectomy by open or transurethral techniques usually destroys the function of the internal sphincter (bladder neck), which is the first line of defense against incontinence. Urinary continence then depends upon the intrinsic smooth muscle sphincter of the membranous urethra and the striated external sphincter. Unfortunately, a significant incidence of membranous urethral stricture occurs after a prostatic operation. Most such strictures can be managed with periodic dilatation but some are difficult and dangerous to dilate. Complications such as recurrent acute retention, bacteremia, false passages, stone formation, fistulas and so forth are indications for surgical cure of the stricture. However, can urethroplasty of the membranous urethra be carried out in these patients without inevitable incontinence? At our center 33 prostatectomized patients have had a 2-stage urethroplasty for refractory membranous urethral strictures. Nine patients had troublesome stress incontinence after the first-stage operation but only 4 of these had continuing incontinence after the second-stage operation. These patients had been noted to have transient postoperative stress incontinence after the prostatectomy. Although there is a risk of incontinence after urethroplasty of the membranous urethra in prostatectomized patients, the risk is sufficiently low that the operation should not be denied patients with refractory strictures in whom the only alternative eventually will be some form of urinary diversion.", "contents": "Urinary continence after repair of membranous urethral stricture in prostatectomized patients. Prostatectomy by open or transurethral techniques usually destroys the function of the internal sphincter (bladder neck), which is the first line of defense against incontinence. Urinary continence then depends upon the intrinsic smooth muscle sphincter of the membranous urethra and the striated external sphincter. Unfortunately, a significant incidence of membranous urethral stricture occurs after a prostatic operation. Most such strictures can be managed with periodic dilatation but some are difficult and dangerous to dilate. Complications such as recurrent acute retention, bacteremia, false passages, stone formation, fistulas and so forth are indications for surgical cure of the stricture. However, can urethroplasty of the membranous urethra be carried out in these patients without inevitable incontinence? At our center 33 prostatectomized patients have had a 2-stage urethroplasty for refractory membranous urethral strictures. Nine patients had troublesome stress incontinence after the first-stage operation but only 4 of these had continuing incontinence after the second-stage operation. These patients had been noted to have transient postoperative stress incontinence after the prostatectomy. Although there is a risk of incontinence after urethroplasty of the membranous urethra in prostatectomized patients, the risk is sufficiently low that the operation should not be denied patients with refractory strictures in whom the only alternative eventually will be some form of urinary diversion."} {"id": "PMID:1263314", "title": "Mucoid cysts of the penile skin.", "content": "A study of 28 patients with mucoid cysts of the penile skin is reported. The lesions were seldom diagnosed correctly, either clinically or pathologically. The distinctive histologic features of the cysts include a lining of stratified columnar epithelium, often associated with intra-epithelial mucous cells and/or mucous glands. These cysts most likely arise from ectopic urethral mucosa sequestered in the penile skin during embryologic development.", "contents": "Mucoid cysts of the penile skin. A study of 28 patients with mucoid cysts of the penile skin is reported. The lesions were seldom diagnosed correctly, either clinically or pathologically. The distinctive histologic features of the cysts include a lining of stratified columnar epithelium, often associated with intra-epithelial mucous cells and/or mucous glands. These cysts most likely arise from ectopic urethral mucosa sequestered in the penile skin during embryologic development."} {"id": "PMID:1263315", "title": "Early carcinoma of the prostate: comparison of stages A and B.", "content": "Stage A--occult, latent, preoperatively undiagnosed, incidentally found, stage I or T0--carcinoma of the prostate has been considered to be an earlier stage than stage B--II, T1 or T2, palpable nodule. In a comparative study of 118 patients with stage A lesions and 115 patients with stage B lesions we have found more focal lesions in A than in B. The A lesions were also less highly malignant than the B. However, the survival of patients with A lesions was a little less than those with B lesions. Age differences and more extensive growth before a detection may account for the differences. Patients with diffuse lesions and those with the more highly malignant lesions had a shorter survival than those with focal lesions and with a lower grade of malignancy in stages A and B. All available preoperative diagnostic data and a through histopathological examination of the surgical specimen are necessary to accurately stage prostatic carcinoma. Other well recognized diagnostic tests, such as the lymphangiogram, acid phosphatase value bone scan and so forth, are also necessary to accurately assess the extent of the disease.", "contents": "Early carcinoma of the prostate: comparison of stages A and B. Stage A--occult, latent, preoperatively undiagnosed, incidentally found, stage I or T0--carcinoma of the prostate has been considered to be an earlier stage than stage B--II, T1 or T2, palpable nodule. In a comparative study of 118 patients with stage A lesions and 115 patients with stage B lesions we have found more focal lesions in A than in B. The A lesions were also less highly malignant than the B. However, the survival of patients with A lesions was a little less than those with B lesions. Age differences and more extensive growth before a detection may account for the differences. Patients with diffuse lesions and those with the more highly malignant lesions had a shorter survival than those with focal lesions and with a lower grade of malignancy in stages A and B. All available preoperative diagnostic data and a through histopathological examination of the surgical specimen are necessary to accurately stage prostatic carcinoma. Other well recognized diagnostic tests, such as the lymphangiogram, acid phosphatase value bone scan and so forth, are also necessary to accurately assess the extent of the disease."} {"id": "PMID:1263316", "title": "Treatment of advanced carcinoma of the prostate with estramustine phosphate.", "content": "Estramustine phosphate has been useful in the treatment of advanced carcinoma of the prostate. Objective remissions were obtained with this therapy in 6 of 17 patients (35 per cent). The results presented herein indicate that the clinical response is to a certain extent caused by an estrogen effect, which was clearly demonstrable in a previously untreated patient. A specific cytostatic effect of estramustine phosphate, which is not yet clearly explained, may be responsible for remissions in some patients who have become resistant to conventional hormonal treatment.", "contents": "Treatment of advanced carcinoma of the prostate with estramustine phosphate. Estramustine phosphate has been useful in the treatment of advanced carcinoma of the prostate. Objective remissions were obtained with this therapy in 6 of 17 patients (35 per cent). The results presented herein indicate that the clinical response is to a certain extent caused by an estrogen effect, which was clearly demonstrable in a previously untreated patient. A specific cytostatic effect of estramustine phosphate, which is not yet clearly explained, may be responsible for remissions in some patients who have become resistant to conventional hormonal treatment."} {"id": "PMID:1263317", "title": "Extended therapy of stage D carcinoma of the prostate with oral estramustine phosphate.", "content": "We treated 50 patients with stage D carcinoma of the prostate with 15 mg. per kg. per day oral estramustine phosphate for 3 to 24 months. We are able to evaluate 44 patients. Objective remissions were induced in 8 of the 44 patients (19 per cent) and subjective remission occurred in all objective responders and in 7 additional patients for a subjective response of 15 of 44 (36 per cent). No hematologic or renal toxicity was encountered. Transient nausea occurred early in half of the patients and was dose limiting in 3 patients. One case of hepatic toxicity was seen. Oral estramustine phosphate is well tolerated and long-term therapy is feasible.", "contents": "Extended therapy of stage D carcinoma of the prostate with oral estramustine phosphate. We treated 50 patients with stage D carcinoma of the prostate with 15 mg. per kg. per day oral estramustine phosphate for 3 to 24 months. We are able to evaluate 44 patients. Objective remissions were induced in 8 of the 44 patients (19 per cent) and subjective remission occurred in all objective responders and in 7 additional patients for a subjective response of 15 of 44 (36 per cent). No hematologic or renal toxicity was encountered. Transient nausea occurred early in half of the patients and was dose limiting in 3 patients. One case of hepatic toxicity was seen. Oral estramustine phosphate is well tolerated and long-term therapy is feasible."} {"id": "PMID:1263318", "title": "Urinary supersaturation with calcium oxalate before and during orthophosphate therapy.", "content": "The concentrations of sodium, potassium, calcium, magnesium, phosphorus, sulfate, citrate and oxalate in the urine of normal subjects were compared to the concentrations in urine of calcium oxalate stone-forming patients. Because of the large volume excreted by stone-forming patients the urine contained less concentrations of sodium, potassium, magnesium, phosphorus, sulfate and citrate than did the urine from normal subjects. The urinary concentrations of calcium and oxalate were similar in the 2 groups and, thus, the calculated supersaturation of calcium oxalate was greater in the urine of stone-forming patients than in the urine of normal subjects. Orthophosphate therapy increased the urinary concentration of alkali ions and phosphate but reduced urinary calcium concentration, thereby causing a reduction in urine supersaturation with calcium oxalate. There was no discernible correlation between the phosphate-induced changes in urine supersaturation and the presence or absence of continued calculus formation.", "contents": "Urinary supersaturation with calcium oxalate before and during orthophosphate therapy. The concentrations of sodium, potassium, calcium, magnesium, phosphorus, sulfate, citrate and oxalate in the urine of normal subjects were compared to the concentrations in urine of calcium oxalate stone-forming patients. Because of the large volume excreted by stone-forming patients the urine contained less concentrations of sodium, potassium, magnesium, phosphorus, sulfate and citrate than did the urine from normal subjects. The urinary concentrations of calcium and oxalate were similar in the 2 groups and, thus, the calculated supersaturation of calcium oxalate was greater in the urine of stone-forming patients than in the urine of normal subjects. Orthophosphate therapy increased the urinary concentration of alkali ions and phosphate but reduced urinary calcium concentration, thereby causing a reduction in urine supersaturation with calcium oxalate. There was no discernible correlation between the phosphate-induced changes in urine supersaturation and the presence or absence of continued calculus formation."} {"id": "PMID:1263319", "title": "Amyloidosis of the lower genitourinary tract.", "content": "Three patients with amyloidosis of the lower genitourinary tract are described. In the cases of primary localized amyloidosis of the urethra and primary systemic amyloidosis involving the prostate the clinical presentation mimicked cancer of the respective sites. In the case of secondary localized amyloidosis of the seminal vesicles chronic perineal pain suggested seminal vesiculitis.", "contents": "Amyloidosis of the lower genitourinary tract. Three patients with amyloidosis of the lower genitourinary tract are described. In the cases of primary localized amyloidosis of the urethra and primary systemic amyloidosis involving the prostate the clinical presentation mimicked cancer of the respective sites. In the case of secondary localized amyloidosis of the seminal vesicles chronic perineal pain suggested seminal vesiculitis."} {"id": "PMID:1263321", "title": "Carbon dioxide urethral pressure profile.", "content": "In an evaluation of patients with lower urinary tract symptoms, particularly incontinence, the role played by the urethra is crucial. One of the most important methods of evaluation of urethral dysfunction is the urethral pressure profile. From among the many simple and more sophisticated methods of urethral pressure profile measurements we have chosen to describe a simple office procedure and a reliable method of urethral pressure profile evaluation, using the carbon dioxide cystometer. Slow withdrawal of the special catheter connected to the carbon dioxide cystometer allows the determination of the resistance of the urehtral wall at sequential centimeter levels along the entire length of the urethra. Carbon dioxide urethral pressure profile is a safe office procedure that is easy to perform for immediate recording and interpretation of results. The cystometer is easy to calibrate. We have had no complications in 450 consecutive urethral pressure profile determinations. The shortcoming of the procedure is the compressibility of the gas (carbon dioxide), giving a lag in the register's response to pressure differential. The use of carbon dioxide urethral pressure profile is demonstrated in male incontinence, in female incontinence and in patients with neurogenic bladder dysfunction, and the results are discussed.", "contents": "Carbon dioxide urethral pressure profile. In an evaluation of patients with lower urinary tract symptoms, particularly incontinence, the role played by the urethra is crucial. One of the most important methods of evaluation of urethral dysfunction is the urethral pressure profile. From among the many simple and more sophisticated methods of urethral pressure profile measurements we have chosen to describe a simple office procedure and a reliable method of urethral pressure profile evaluation, using the carbon dioxide cystometer. Slow withdrawal of the special catheter connected to the carbon dioxide cystometer allows the determination of the resistance of the urehtral wall at sequential centimeter levels along the entire length of the urethra. Carbon dioxide urethral pressure profile is a safe office procedure that is easy to perform for immediate recording and interpretation of results. The cystometer is easy to calibrate. We have had no complications in 450 consecutive urethral pressure profile determinations. The shortcoming of the procedure is the compressibility of the gas (carbon dioxide), giving a lag in the register's response to pressure differential. The use of carbon dioxide urethral pressure profile is demonstrated in male incontinence, in female incontinence and in patients with neurogenic bladder dysfunction, and the results are discussed."} {"id": "PMID:1263322", "title": "Voiding cystourethrography with patient in the standing position.", "content": "The method for voiding cystourethrography with the patient in the standing position is described. Cystourethrography is much easier to perform when the patient is standing and the results are as good as those obtained with the patient supine.", "contents": "Voiding cystourethrography with patient in the standing position. The method for voiding cystourethrography with the patient in the standing position is described. Cystourethrography is much easier to perform when the patient is standing and the results are as good as those obtained with the patient supine."} {"id": "PMID:1263323", "title": "Surgical correction of vesicoureteral reflux in children with neurogenic bladder.", "content": "The reported success rate for correction of vesicoureteral reflux in the neurogenic bladder has been low. Reflux was corrected in 33 of 37 ureters in 23 selected children with neurogenic bladder-treated by reimplantation. Selection was based on good bladder capacity, little or no trabeculation and the expectation that the bladder would be useful in future management of the patient. Preoperative preparation and surgical technique are emphasized.", "contents": "Surgical correction of vesicoureteral reflux in children with neurogenic bladder. The reported success rate for correction of vesicoureteral reflux in the neurogenic bladder has been low. Reflux was corrected in 33 of 37 ureters in 23 selected children with neurogenic bladder-treated by reimplantation. Selection was based on good bladder capacity, little or no trabeculation and the expectation that the bladder would be useful in future management of the patient. Preoperative preparation and surgical technique are emphasized."} {"id": "PMID:1263324", "title": "Our experience with the adrenogenital syndrome: a review of 16 cases.", "content": "An analysis of 16 children with the adrenogenital syndrome illustrates the diversity of the clinical and laboratory features of the disorder. The need for critical periodic evaluation of individual assessment of each child and the dosage of corticosteroids being used is emphasized.", "contents": "Our experience with the adrenogenital syndrome: a review of 16 cases. An analysis of 16 children with the adrenogenital syndrome illustrates the diversity of the clinical and laboratory features of the disorder. The need for critical periodic evaluation of individual assessment of each child and the dosage of corticosteroids being used is emphasized."} {"id": "PMID:1263325", "title": "Case report: simple renal cyst in child.", "content": "A case of a large renal cyst of the right kidney suggesting a nephroblastoma is reported. Preoperative differentiation was diffucult.", "contents": "Case report: simple renal cyst in child. A case of a large renal cyst of the right kidney suggesting a nephroblastoma is reported. Preoperative differentiation was diffucult."} {"id": "PMID:1263326", "title": "Intermittent bladder paresis in the pseudoclaudication syndrome.", "content": "The pseudoclaudication syndrome, now a well known neurological entity, can simulate intermittent claudication of arterial origin in its clinical appearance. Walking and sometimes simply standing upright for a while can cause transitory pain, numbness or weakness in the legs. The symptoms are caused by entrapment of the cauda equina fibers. Intermittent bladder paresis with total inability of micturition despite urgency to void may sometimes be a prominent feature of the syndrome, a fact that seems to be less well known as seen from a review of the literature.", "contents": "Intermittent bladder paresis in the pseudoclaudication syndrome. The pseudoclaudication syndrome, now a well known neurological entity, can simulate intermittent claudication of arterial origin in its clinical appearance. Walking and sometimes simply standing upright for a while can cause transitory pain, numbness or weakness in the legs. The symptoms are caused by entrapment of the cauda equina fibers. Intermittent bladder paresis with total inability of micturition despite urgency to void may sometimes be a prominent feature of the syndrome, a fact that seems to be less well known as seen from a review of the literature."} {"id": "PMID:1263327", "title": "Neisseria catarrhal urethritis: a case report.", "content": "A case of Neisseria catarrhal urethritis presenting with a gonorrhea-like discharge is reported. Prior treatment was not a factor in its isolation and the patient responded well to penicillin.", "contents": "Neisseria catarrhal urethritis: a case report. A case of Neisseria catarrhal urethritis presenting with a gonorrhea-like discharge is reported. Prior treatment was not a factor in its isolation and the patient responded well to penicillin."} {"id": "PMID:1263328", "title": "The characteristics of diastolic pressure-volume relationships in primary myocardial disease.", "content": "Utilizing the pressure-volume relationship, the indices of left ventricular diastolic compliance, SV/EDP-DP, dV/dP, and dV/VdP, ventricular stiffness index, I/P(dV/dP), and myocardial stiffness index, I/S(dD/dS) were evaluated of seven patients with normal left ventricle, eleven patients with hypertrophic and seven with congestive type of primary myocardial disease. Myocardial stiffness index was obtained from the equation of S = aekD, where S is a wall stress, a; a constant, D; a length of short axis, K; a stiffness constant. The mean values and standard errors of the means of SV/EDP DP, dV/dP, dV/VdP, I/P(dV/dP), and I/S(dD/dS) for normal group are 16.7 +/- 8.7 (ml/mmHg), 16.03 +/- 6.98 (ml/mmHg), 0.1259 +/- 0.0447 (mmHg-1), 0.0059 +/- 0.0032 (ml-1) and 0.603 +/- 0.153 (cm-1), for hypertrophic type are 10.5 +/- 5.5 (ml/mmHg), 7.23 +/- 7.42 (ml/mmHg), 0.0599 +/- 0.0736 (mmHg-1), 0.0174 +/- 0.0097 (ml-1) and 1.3555 +/- 0.3395 (cm-1), and for congestive type are 17.5 +/- 3.4 (ml/mmHg), 3.91 +/- 2.13 (ml/mmHg), 0.0250 +/- 0.0239 (mmHg-1), 0.0308 +/- 0.0126 (ml-1), and 3.287 +/- 1.272 (cm-1). There were highly significant differences between normal and primary myocardial disease in each indices except SV/EDP-DP. I/P(dV/dP), and I/S(dD/dS) had highly significant differences between hypertrophic and congestive type, the latter is stiffer than the former. The compliance index was not sensitive enough to separate two types of primary myocardial disease.", "contents": "The characteristics of diastolic pressure-volume relationships in primary myocardial disease. Utilizing the pressure-volume relationship, the indices of left ventricular diastolic compliance, SV/EDP-DP, dV/dP, and dV/VdP, ventricular stiffness index, I/P(dV/dP), and myocardial stiffness index, I/S(dD/dS) were evaluated of seven patients with normal left ventricle, eleven patients with hypertrophic and seven with congestive type of primary myocardial disease. Myocardial stiffness index was obtained from the equation of S = aekD, where S is a wall stress, a; a constant, D; a length of short axis, K; a stiffness constant. The mean values and standard errors of the means of SV/EDP DP, dV/dP, dV/VdP, I/P(dV/dP), and I/S(dD/dS) for normal group are 16.7 +/- 8.7 (ml/mmHg), 16.03 +/- 6.98 (ml/mmHg), 0.1259 +/- 0.0447 (mmHg-1), 0.0059 +/- 0.0032 (ml-1) and 0.603 +/- 0.153 (cm-1), for hypertrophic type are 10.5 +/- 5.5 (ml/mmHg), 7.23 +/- 7.42 (ml/mmHg), 0.0599 +/- 0.0736 (mmHg-1), 0.0174 +/- 0.0097 (ml-1) and 1.3555 +/- 0.3395 (cm-1), and for congestive type are 17.5 +/- 3.4 (ml/mmHg), 3.91 +/- 2.13 (ml/mmHg), 0.0250 +/- 0.0239 (mmHg-1), 0.0308 +/- 0.0126 (ml-1), and 3.287 +/- 1.272 (cm-1). There were highly significant differences between normal and primary myocardial disease in each indices except SV/EDP-DP. I/P(dV/dP), and I/S(dD/dS) had highly significant differences between hypertrophic and congestive type, the latter is stiffer than the former. The compliance index was not sensitive enough to separate two types of primary myocardial disease."} {"id": "PMID:1263330", "title": "Column chromatographic analysis of relationship between hypertension-inducing potency and renin content of kidney extract.", "content": "The relationship between hypertension-inducing potency and renin content of kidney extract was analyzed in rats using Sephadex G-100, CM-Sephadex C-50, DEAE-Cellulose or Concanavalin A-Sepharose column chromatography. Hypertension-inducing potency of each fraction obtained was evaluated in the basis of the final blood pressure level attained by repeated injections into the test animals for 10 days. Hypertension-inducing potency was found mainly in the renin-contaning fractions. And it seems reasonable to conclude that renin is implicated in the pathogenesis of hypertension produced by kidney extract. However, there were significant discrepancies between hypertension-inducing potency and renin content of subdivided fractions of these renin-containing eluates. Possible explantations for the discrepancies disclosed--including the possibility of the involvement of an unknown substance(s)--have been discussed. In addition, it was suggested from the results of Concanavalin A-Sepharose chromatography that rat renal renin has a glycoprotein nature.", "contents": "Column chromatographic analysis of relationship between hypertension-inducing potency and renin content of kidney extract. The relationship between hypertension-inducing potency and renin content of kidney extract was analyzed in rats using Sephadex G-100, CM-Sephadex C-50, DEAE-Cellulose or Concanavalin A-Sepharose column chromatography. Hypertension-inducing potency of each fraction obtained was evaluated in the basis of the final blood pressure level attained by repeated injections into the test animals for 10 days. Hypertension-inducing potency was found mainly in the renin-contaning fractions. And it seems reasonable to conclude that renin is implicated in the pathogenesis of hypertension produced by kidney extract. However, there were significant discrepancies between hypertension-inducing potency and renin content of subdivided fractions of these renin-containing eluates. Possible explantations for the discrepancies disclosed--including the possibility of the involvement of an unknown substance(s)--have been discussed. In addition, it was suggested from the results of Concanavalin A-Sepharose chromatography that rat renal renin has a glycoprotein nature."} {"id": "PMID:1263331", "title": "Histochemical studies of monoamine oxidase in experimental myocardial infarctions.", "content": "Sequential histochemical studies were conducted to determine the level of monoamine oxidase (MAO) activity in the infarcted tissue of the experimental myocardial infarction in dog. MAO activity was not found in the normal heart muscle, but the activities were present in the wall of the coronary artery histochemically. Fibroblasts and collagen fibers began to take the place of the destroyed heart muscles in the infarcted area from 10 days after the coronary occlusion in dogs, and MAO activities were noted sporadically in the fibroblasts and the interstices of the collagen fibers in the infarcted area. MAO activities increased histochemically in the fibroblasts and the fiber interstices in the infarcted area 10 days or more after the coronary occlusion. These findings suggested the presence of the active collagen metabolism outside the myocardial cells in the infarcted area in the recovery stage of the experimental myocardial infarction. It was also suggested that the interstices of the collagen fibers in the myocardial wall constituted the lymphatic ducts outside the blood vessels and that the MAO activity in serum determined by the method in which tryptamine hydrochloride was used as substrate might indicate the grade of fibrosis of the myocardial tissue in the infarcted areas.", "contents": "Histochemical studies of monoamine oxidase in experimental myocardial infarctions. Sequential histochemical studies were conducted to determine the level of monoamine oxidase (MAO) activity in the infarcted tissue of the experimental myocardial infarction in dog. MAO activity was not found in the normal heart muscle, but the activities were present in the wall of the coronary artery histochemically. Fibroblasts and collagen fibers began to take the place of the destroyed heart muscles in the infarcted area from 10 days after the coronary occlusion in dogs, and MAO activities were noted sporadically in the fibroblasts and the interstices of the collagen fibers in the infarcted area. MAO activities increased histochemically in the fibroblasts and the fiber interstices in the infarcted area 10 days or more after the coronary occlusion. These findings suggested the presence of the active collagen metabolism outside the myocardial cells in the infarcted area in the recovery stage of the experimental myocardial infarction. It was also suggested that the interstices of the collagen fibers in the myocardial wall constituted the lymphatic ducts outside the blood vessels and that the MAO activity in serum determined by the method in which tryptamine hydrochloride was used as substrate might indicate the grade of fibrosis of the myocardial tissue in the infarcted areas."} {"id": "PMID:1263332", "title": "Non-invasive assessment of the performance of the right heart during dynamic exercise, a study of left-sided heart disease.", "content": "A simplified, non-invasive method for assessment of the performance of the right heart during supine leg exercise was described, which necessitated no more than a bicycle \"ergometer\" for leg exercise, a radiocardiograph for recording cardiac index (CI) and a \"water\" manometer for measuring cubital venous pressure (VP). Because the use of a cardiac catheter was omitted, right atrial pressure (RA), right ventricular diastolic pressure (RVd) or pulmonary arterial pressure (PA) were not measured. In 11 healthy subjects and 25 patients with primarily left-sided valvular disease and hypertension, the observed shift of CI-VP plot with exercise was similar to the published records of exercise-induced shift of CI-RA plot or CI-RVd plot in normal subjects and the same types of heart disease. With levels of load used in this study, a dividing line separating normal from abnormal elevation of VP during supine leg exercise (deltaVP) could be drawn at deltaVP = 35 mm H2O, because (1) none of the healthy subjects had deltaVP in excess of 35 mm H2O and (2) in these types of heart disease, deltaVP in excess of 35 mm H2O was always associated with a \"subnormal\" increase in CI (deltaCI less than 0.8 lit. min-1. M-2) with exercise, except in a few cases who appeared, clinically, to be in what may be termed \"latent heart failure\". Factors probably responsible for an impaired pumping ability of the right heart during exercise in left-sided heart disease were discussed, in relation to deltaVP.", "contents": "Non-invasive assessment of the performance of the right heart during dynamic exercise, a study of left-sided heart disease. A simplified, non-invasive method for assessment of the performance of the right heart during supine leg exercise was described, which necessitated no more than a bicycle \"ergometer\" for leg exercise, a radiocardiograph for recording cardiac index (CI) and a \"water\" manometer for measuring cubital venous pressure (VP). Because the use of a cardiac catheter was omitted, right atrial pressure (RA), right ventricular diastolic pressure (RVd) or pulmonary arterial pressure (PA) were not measured. In 11 healthy subjects and 25 patients with primarily left-sided valvular disease and hypertension, the observed shift of CI-VP plot with exercise was similar to the published records of exercise-induced shift of CI-RA plot or CI-RVd plot in normal subjects and the same types of heart disease. With levels of load used in this study, a dividing line separating normal from abnormal elevation of VP during supine leg exercise (deltaVP) could be drawn at deltaVP = 35 mm H2O, because (1) none of the healthy subjects had deltaVP in excess of 35 mm H2O and (2) in these types of heart disease, deltaVP in excess of 35 mm H2O was always associated with a \"subnormal\" increase in CI (deltaCI less than 0.8 lit. min-1. M-2) with exercise, except in a few cases who appeared, clinically, to be in what may be termed \"latent heart failure\". Factors probably responsible for an impaired pumping ability of the right heart during exercise in left-sided heart disease were discussed, in relation to deltaVP."} {"id": "PMID:1263333", "title": "[Therapeutic effect of amoxicillin in the surgical field (author's transl)].", "content": "1. Amoxicillin was used for treatment of 15 cases of infectious diseases in the surgical field and for prevention of 4 cases of postoperative infection, and good result was obtained in all 19 cases. Especially in the latter 4 cases, amoxicillin showed good preventive effect. 2. Any side effect probably due to amoxicillin was observed in no case. 3. Amoxicillin at a daily dose of 1,000 mg (potency) exhibited sufficient effect in treatment of infectious diseases in the surgical field and in prevention of postoperative infection.", "contents": "[Therapeutic effect of amoxicillin in the surgical field (author's transl)]. 1. Amoxicillin was used for treatment of 15 cases of infectious diseases in the surgical field and for prevention of 4 cases of postoperative infection, and good result was obtained in all 19 cases. Especially in the latter 4 cases, amoxicillin showed good preventive effect. 2. Any side effect probably due to amoxicillin was observed in no case. 3. Amoxicillin at a daily dose of 1,000 mg (potency) exhibited sufficient effect in treatment of infectious diseases in the surgical field and in prevention of postoperative infection."} {"id": "PMID:1263337", "title": "[Clinical study of amoxicillin used for treatment of infections of the lower urinary tracts (author's transl)].", "content": "The following results were obtained from treatment of 29 cases of lower urinary tract infections with amoxicillin. 1. Amoxicillin was remarkably effective in 13 cases of acute cystitis, in terms of effect according to dose and bacterial species. 2. The effective rate of amoxicillin in 10 cases of chronic cystitis amounted only to 30% due to complications and resistant bacteria. (The group given 1,500 mg/day was a little higher in the effective rate than the 750 mg/day group.) 3. Amoxicillin was low in effect against infections with Pseudomonas aeruginosa and hardly effective against bacteria resistant to amoxicillin. 4. So far as this study is concerned, amoxicillin produced good clinical results at a half dose of ampicillin, as in the fundamental experiment. 5. Any severe side effect was observed in no case.", "contents": "[Clinical study of amoxicillin used for treatment of infections of the lower urinary tracts (author's transl)]. The following results were obtained from treatment of 29 cases of lower urinary tract infections with amoxicillin. 1. Amoxicillin was remarkably effective in 13 cases of acute cystitis, in terms of effect according to dose and bacterial species. 2. The effective rate of amoxicillin in 10 cases of chronic cystitis amounted only to 30% due to complications and resistant bacteria. (The group given 1,500 mg/day was a little higher in the effective rate than the 750 mg/day group.) 3. Amoxicillin was low in effect against infections with Pseudomonas aeruginosa and hardly effective against bacteria resistant to amoxicillin. 4. So far as this study is concerned, amoxicillin produced good clinical results at a half dose of ampicillin, as in the fundamental experiment. 5. Any severe side effect was observed in no case."} {"id": "PMID:1263338", "title": "[Clinical study of amoxicillin used in the otorhinolaryngological field (author's transl)].", "content": "The following results were obtained from oral administration of amoxicillin to 20 cases of acute otorhinolaryngological infections for 5 consecutive days; the daily dose was 1,500 mg for adult and 750mg for child. 1. Six cases with acute tonsillitis, 6 with acute pharyngolaryngitis, 5 with acute otitis media, 2 with furuncle of the nose and 1 with acute laryngitis were treated with amoxicillin. This drug was remarkably effective in 2 of 20 cases in total, effective in 15, slightly effective in 1 and non-effective in 2. 2. The sensitivity test to amoxicillin by the use of ampicillin sensitivity disk revealed that all of isolated bacteria were remarkably sensitive to amoxicillin, except one strain of Staphylococcus aureus which was moderately sensitive. 3. Side effect occurred at the rate of 25%; 4 cases of eruption and 1 of esophagitis. Other severe side effects were not observed. From the above results, amoxicillin is considered to be an effective drug for clinical application in the otorhinolaryngological field.", "contents": "[Clinical study of amoxicillin used in the otorhinolaryngological field (author's transl)]. The following results were obtained from oral administration of amoxicillin to 20 cases of acute otorhinolaryngological infections for 5 consecutive days; the daily dose was 1,500 mg for adult and 750mg for child. 1. Six cases with acute tonsillitis, 6 with acute pharyngolaryngitis, 5 with acute otitis media, 2 with furuncle of the nose and 1 with acute laryngitis were treated with amoxicillin. This drug was remarkably effective in 2 of 20 cases in total, effective in 15, slightly effective in 1 and non-effective in 2. 2. The sensitivity test to amoxicillin by the use of ampicillin sensitivity disk revealed that all of isolated bacteria were remarkably sensitive to amoxicillin, except one strain of Staphylococcus aureus which was moderately sensitive. 3. Side effect occurred at the rate of 25%; 4 cases of eruption and 1 of esophagitis. Other severe side effects were not observed. From the above results, amoxicillin is considered to be an effective drug for clinical application in the otorhinolaryngological field."} {"id": "PMID:1263339", "title": "[Clinical results in treatment of purulent dermatoses with amoxicillin (author's transl)].", "content": "The following are the clinical results of amoxicillin used for 21 cases of purulent dermatoses. Amoxicillin was remarkably effective in 5 of total 21 cases, effective in 12, slightly effective in 2 and non-effective in 2; that is, amoxicillin produced good results. One case each of drug eruption and abdominal distention were observed as side effects. Judging from its level in the blood, amoxicillin is expected to exhibit good therapeutical effect at a daily dose of 750 approximately 1,000 mg. Amoxicillin can be considered to be an effective drug for purulent dermatoses without severe side effect.", "contents": "[Clinical results in treatment of purulent dermatoses with amoxicillin (author's transl)]. The following are the clinical results of amoxicillin used for 21 cases of purulent dermatoses. Amoxicillin was remarkably effective in 5 of total 21 cases, effective in 12, slightly effective in 2 and non-effective in 2; that is, amoxicillin produced good results. One case each of drug eruption and abdominal distention were observed as side effects. Judging from its level in the blood, amoxicillin is expected to exhibit good therapeutical effect at a daily dose of 750 approximately 1,000 mg. Amoxicillin can be considered to be an effective drug for purulent dermatoses without severe side effect."} {"id": "PMID:1263340", "title": "[Experience with amoxicillin therapy in urological field (author's transl)].", "content": "Amoxicillin (AMPC), an oral preparation of broad spectrum synthetic penicillin, was used for treatment of 10 cases with urological infection, and the following results were obtained. 1. AMPC at a daily dose of 750 approximately 1,500 mg was administered for 7 approximately 49 days to 5 cases of acute cystitis, 2 cases of acute epididymitis and one case each of calculous hydronephrosis, chronic prostatitis and postoperative cystitis. As the result, AMPC was found remarkably effective in 2 cases, effective in 7 cases and ineffective in one case; that is, the effective rate was 9/10 (90.0%). 2. Total 8 strains of bacteria, comprising 5 strains of Escherichia coli and one strain each of Klebsiella, Staphylococcus epidermidis and Pseudomonas, were isolated from the urine. These bacteria were relatively responsive to AMPC as well as to ABPC. 3. The side effect possibly due to AMPC was slight gastro-intestinal disorder only in 2 of 10 cases. No other side effect was observed.", "contents": "[Experience with amoxicillin therapy in urological field (author's transl)]. Amoxicillin (AMPC), an oral preparation of broad spectrum synthetic penicillin, was used for treatment of 10 cases with urological infection, and the following results were obtained. 1. AMPC at a daily dose of 750 approximately 1,500 mg was administered for 7 approximately 49 days to 5 cases of acute cystitis, 2 cases of acute epididymitis and one case each of calculous hydronephrosis, chronic prostatitis and postoperative cystitis. As the result, AMPC was found remarkably effective in 2 cases, effective in 7 cases and ineffective in one case; that is, the effective rate was 9/10 (90.0%). 2. Total 8 strains of bacteria, comprising 5 strains of Escherichia coli and one strain each of Klebsiella, Staphylococcus epidermidis and Pseudomonas, were isolated from the urine. These bacteria were relatively responsive to AMPC as well as to ABPC. 3. The side effect possibly due to AMPC was slight gastro-intestinal disorder only in 2 of 10 cases. No other side effect was observed."} {"id": "PMID:1263342", "title": "[Clinical experience with amoxicillin (Pacetocin 'Kyowa') in urology (author's transl)].", "content": "Amoxicillin (Pacetocin 'Kyowa') was orally administered in a daily dose of 1 g (potency) to 5 cases with urological infections and 15 cases with postoperative infections. As a result the drug was found remarkably effective in one case, effective in 15 cases and ineffective in 3 cases; in one case, the response to amoxicillin was uninterpretable. No severe side effect was observed during the treatment.", "contents": "[Clinical experience with amoxicillin (Pacetocin 'Kyowa') in urology (author's transl)]. Amoxicillin (Pacetocin 'Kyowa') was orally administered in a daily dose of 1 g (potency) to 5 cases with urological infections and 15 cases with postoperative infections. As a result the drug was found remarkably effective in one case, effective in 15 cases and ineffective in 3 cases; in one case, the response to amoxicillin was uninterpretable. No severe side effect was observed during the treatment."} {"id": "PMID:1263345", "title": "[Clinical experience with amoxicillin in otorhinolaryngology (author's transl)].", "content": "This paper reports the clinical trial of amoxicillin. (1) A daily dose of 750 approximately 1,000 mg of amoxicillin was orally administered for 3 approximately 12 days to 20 patients, 7 of which were with acute suppurative tympanitis, 3 with furuncle of the ear, 2 with furuncle of the nose and 8 with acute amygdalitis. As a result, amoxicillin proved remarkably effective or effective in 17 patients (85.0%). (2) Amoxicillin was effective against: Staphylococcus aureus in 10 of 11 patients (90.9%) Staphylococcus epidermidis in 2 of 2 patients (100%) Streptococcus hemolyticus in 3 of 4 patients (75%) Streptococcus viridans in 1 of 1 patient (100%) Diplococcus pneumoniae in 1 of 1 patient (100%) (3) Although one patient developed drug eruption, there were no side effects that necessitated cessation of administration. From the above results, it is concluded that amoxicillin can be used in the treatment of otorhinolaryngologic infections.", "contents": "[Clinical experience with amoxicillin in otorhinolaryngology (author's transl)]. This paper reports the clinical trial of amoxicillin. (1) A daily dose of 750 approximately 1,000 mg of amoxicillin was orally administered for 3 approximately 12 days to 20 patients, 7 of which were with acute suppurative tympanitis, 3 with furuncle of the ear, 2 with furuncle of the nose and 8 with acute amygdalitis. As a result, amoxicillin proved remarkably effective or effective in 17 patients (85.0%). (2) Amoxicillin was effective against: Staphylococcus aureus in 10 of 11 patients (90.9%) Staphylococcus epidermidis in 2 of 2 patients (100%) Streptococcus hemolyticus in 3 of 4 patients (75%) Streptococcus viridans in 1 of 1 patient (100%) Diplococcus pneumoniae in 1 of 1 patient (100%) (3) Although one patient developed drug eruption, there were no side effects that necessitated cessation of administration. From the above results, it is concluded that amoxicillin can be used in the treatment of otorhinolaryngologic infections."} {"id": "PMID:1263346", "title": "[Blood concentration and urinary excretion in human of OE-7, a gastric hard capsule containing enteric-coated granules. I (author's transl)].", "content": "The investigation of physico-chemical properties and measurement of blood concentration and amount of excretion into urine in human of OE-7 (main constituent is erythromycin stearate) were performed as the fundamental studies. The results obtained were as follows; i) OE-7 is a gastric hard capsule containing enteric coated granules. ii) The contents of OE-7 capsule (granules) were resistant to acid and was favarable in the enteric solubility. iii) In comparison with the conventional erythromycin stearate capsule in healthy adults, OE-7 showed a relatively small individual difference in blood concentration after administration. iv) OE-7 was higher in the mean blood concentration and was superior in the persistence of effective blood concentration compared with the conventional erythromycin stearate capsules.", "contents": "[Blood concentration and urinary excretion in human of OE-7, a gastric hard capsule containing enteric-coated granules. I (author's transl)]. The investigation of physico-chemical properties and measurement of blood concentration and amount of excretion into urine in human of OE-7 (main constituent is erythromycin stearate) were performed as the fundamental studies. The results obtained were as follows; i) OE-7 is a gastric hard capsule containing enteric coated granules. ii) The contents of OE-7 capsule (granules) were resistant to acid and was favarable in the enteric solubility. iii) In comparison with the conventional erythromycin stearate capsule in healthy adults, OE-7 showed a relatively small individual difference in blood concentration after administration. iv) OE-7 was higher in the mean blood concentration and was superior in the persistence of effective blood concentration compared with the conventional erythromycin stearate capsules."} {"id": "PMID:1263348", "title": "Effect of taurine on responses to noradrenaline, acetylcholine and ouabain in isolated auricles from digitalized guinea pigs.", "content": "Responses of the isolated heart from the guinea pig treated chronically with digitoxin until the T wave had disappeared were studied. The development of the abnormal ECG pattern was abolished by a simultaneous injection of taurine and digitoxin. Taurine also inhibited the change by digitoxin of the responses to acetylcholine and ouabain but not to noradrenaline. The causal relationship between the inhibitory effect of taurine and prevention of the development of arrhythmias remains obscure.", "contents": "Effect of taurine on responses to noradrenaline, acetylcholine and ouabain in isolated auricles from digitalized guinea pigs. Responses of the isolated heart from the guinea pig treated chronically with digitoxin until the T wave had disappeared were studied. The development of the abnormal ECG pattern was abolished by a simultaneous injection of taurine and digitoxin. Taurine also inhibited the change by digitoxin of the responses to acetylcholine and ouabain but not to noradrenaline. The causal relationship between the inhibitory effect of taurine and prevention of the development of arrhythmias remains obscure."} {"id": "PMID:1263353", "title": "Comparison of local anesthetic activities between cis and trans isomers of DL-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene.", "content": "The local anesthetic activities of cis- and trans- dl-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene were compared using several methods with guinea-pigs. The cis compound (YAU-17) was 2.9 to 6 times as potent as its trans isomer and exceeded procaine, lidocaine and cocaine in potencies of corneal anesthesia, intracutaneous anesthesia and sciatic nerve block. In another experiment on isolated frog sartorius muscle, all of the local anesthetics suppressed the twitch contractions elicited by stimulation of the sciatic nerve. The neuromuscular blocking activity of the cis compound was more pronounced than that of the trans form. Supersensitivity to noradrenaline was produced by both of the stereoisomers in isolated vas deferens of guinea-pigs although there was no difference in the activity. The sensitizing action was also demonstrable with cocaine and lidocaine but not with procaine. When injected intravenously into mice, the cis compound was twice as toxic as its isomer. It is postulated that stereoselectivity is to some extent involved in the mechanisms of action of the local anesthetic agents.", "contents": "Comparison of local anesthetic activities between cis and trans isomers of DL-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene. The local anesthetic activities of cis- and trans- dl-1-benzoyloxy-2-dimethylamino-1,2,3,4-tetrahydronaphthalene were compared using several methods with guinea-pigs. The cis compound (YAU-17) was 2.9 to 6 times as potent as its trans isomer and exceeded procaine, lidocaine and cocaine in potencies of corneal anesthesia, intracutaneous anesthesia and sciatic nerve block. In another experiment on isolated frog sartorius muscle, all of the local anesthetics suppressed the twitch contractions elicited by stimulation of the sciatic nerve. The neuromuscular blocking activity of the cis compound was more pronounced than that of the trans form. Supersensitivity to noradrenaline was produced by both of the stereoisomers in isolated vas deferens of guinea-pigs although there was no difference in the activity. The sensitizing action was also demonstrable with cocaine and lidocaine but not with procaine. When injected intravenously into mice, the cis compound was twice as toxic as its isomer. It is postulated that stereoselectivity is to some extent involved in the mechanisms of action of the local anesthetic agents."} {"id": "PMID:1263354", "title": "Studies on monoamine oxidase (report XXXIV). Effects of ammonium sulfate on mitochondrial MAO in beef liver.", "content": "The effects of ammonium sulfate on mitochondrial monoamine oxidase (MAO) in beef liver were studied. The initial stage of the reaction was measured with an oxygen electrode and the long term reaction was measured manometrically. With tyramine or benzylamine as substrate, addition of ammonium sulfate increased the initial reaction but decreased the long term reaction. Ammonium sulfate had similar effects on solubilized MAO. Inhibition of MAO activity in both the initial and long term reaction by excess substrate was diminished by addition of ammonium sulfate. The effects of ammonium sulfate on MAO were reversible. Salts having an -SO4 group, such as Na2SO4 and K2SO4, increased MAO activity in the initial reaction while salts having an -NH4 group, such as NH4Cl and NH4NO3, inhibited it. However, all these salts inhibited MAO activity in the long term reaction. The mechanism of activation of MAO activity by addition of ammonium sulfate is discussed.", "contents": "Studies on monoamine oxidase (report XXXIV). Effects of ammonium sulfate on mitochondrial MAO in beef liver. The effects of ammonium sulfate on mitochondrial monoamine oxidase (MAO) in beef liver were studied. The initial stage of the reaction was measured with an oxygen electrode and the long term reaction was measured manometrically. With tyramine or benzylamine as substrate, addition of ammonium sulfate increased the initial reaction but decreased the long term reaction. Ammonium sulfate had similar effects on solubilized MAO. Inhibition of MAO activity in both the initial and long term reaction by excess substrate was diminished by addition of ammonium sulfate. The effects of ammonium sulfate on MAO were reversible. Salts having an -SO4 group, such as Na2SO4 and K2SO4, increased MAO activity in the initial reaction while salts having an -NH4 group, such as NH4Cl and NH4NO3, inhibited it. However, all these salts inhibited MAO activity in the long term reaction. The mechanism of activation of MAO activity by addition of ammonium sulfate is discussed."} {"id": "PMID:1263355", "title": "Effects of Na+ and other monovalent cations on Ca-efflux from synaptosomes.", "content": "Effects of monovalent cations on Ca-efflux were examined in rat brain cortex slices, synaptosomes and synaptic plasma membranes. Effluxes of 45Ca from brain slices and synaptosomes were stimulated by Na+ in medium and the effects of Na+ on the 45Ca-effluxes disappeared at low temperature. Furthermore, we observed that Rb+ had more effect than Na+ on 45Ca-efflux from the synaptosomes, while Li+ had less effect. On the other hand, release of 45Ca from the synaptic plasma membranes which had been preincubated with ATP, MG++ and 45Ca was stimulated by Na+ and Li+. But Cs+ and Rb+ were less effective on the release. These results indicate occurrence of Na-dependent Ca-efflux at nerve endings. However, the assumption that ATP-dependent Ca-binding with synaptic plasma membranes may be a partial reaction of Ca-efflux was not supported by these experiments.", "contents": "Effects of Na+ and other monovalent cations on Ca-efflux from synaptosomes. Effects of monovalent cations on Ca-efflux were examined in rat brain cortex slices, synaptosomes and synaptic plasma membranes. Effluxes of 45Ca from brain slices and synaptosomes were stimulated by Na+ in medium and the effects of Na+ on the 45Ca-effluxes disappeared at low temperature. Furthermore, we observed that Rb+ had more effect than Na+ on 45Ca-efflux from the synaptosomes, while Li+ had less effect. On the other hand, release of 45Ca from the synaptic plasma membranes which had been preincubated with ATP, MG++ and 45Ca was stimulated by Na+ and Li+. But Cs+ and Rb+ were less effective on the release. These results indicate occurrence of Na-dependent Ca-efflux at nerve endings. However, the assumption that ATP-dependent Ca-binding with synaptic plasma membranes may be a partial reaction of Ca-efflux was not supported by these experiments."} {"id": "PMID:1263356", "title": "Centrally mediated cardiovascular responses to intracisternal injections of sympathomimetic amines in anesthetized rats.", "content": "The cardiovascular effects resulting from intracisternal (i.c.) injections of sympathomimetic amines were studied in alpha-chloralose-urethanized rats. Norepinephrine (0.5-5 mug i.c.) caused a typical rise in blood pressure with no significant change in heart rate and a fall in blood pressure with a bradycardia, which were completely blocked after treatment with phentolamine (10-50 mug i.c.) L-isoproterenol (0.05-0.5 mug i.c.) and trimetoquinol (0.5-3 mug i.c.), a beta-sympathomimetic agent, usually caused a fall in blood pressure with a tachycardia, which was reduced after treatment with propranolol (10-50 mug i.c.), but trimetoquinol was inclined to cause a rise in blood pressure with a tachycardia. Epinephrine (5 mug i.c.) showed both centrally mediated alpha- and beta-sympathomimetic effects. Tyramine (0.5-1 mg i.c.) caused mixed blood pressure responses presumably due to a release of norepinephrine and epinephrine, and these responses were partially blocked after treatment with phentolamine (100 mug i.c.) or propranolol (50 mug i.c.). These observations suggest that both alpha- and beta-sensitive adrenergic zones may exist on the vasomotor center of the pons and medulla in rats, and both norepinephrine and epinephrine might centrally play a physiological role as the neurotransmitters controlling blood pressure in rats.", "contents": "Centrally mediated cardiovascular responses to intracisternal injections of sympathomimetic amines in anesthetized rats. The cardiovascular effects resulting from intracisternal (i.c.) injections of sympathomimetic amines were studied in alpha-chloralose-urethanized rats. Norepinephrine (0.5-5 mug i.c.) caused a typical rise in blood pressure with no significant change in heart rate and a fall in blood pressure with a bradycardia, which were completely blocked after treatment with phentolamine (10-50 mug i.c.) L-isoproterenol (0.05-0.5 mug i.c.) and trimetoquinol (0.5-3 mug i.c.), a beta-sympathomimetic agent, usually caused a fall in blood pressure with a tachycardia, which was reduced after treatment with propranolol (10-50 mug i.c.), but trimetoquinol was inclined to cause a rise in blood pressure with a tachycardia. Epinephrine (5 mug i.c.) showed both centrally mediated alpha- and beta-sympathomimetic effects. Tyramine (0.5-1 mg i.c.) caused mixed blood pressure responses presumably due to a release of norepinephrine and epinephrine, and these responses were partially blocked after treatment with phentolamine (100 mug i.c.) or propranolol (50 mug i.c.). These observations suggest that both alpha- and beta-sensitive adrenergic zones may exist on the vasomotor center of the pons and medulla in rats, and both norepinephrine and epinephrine might centrally play a physiological role as the neurotransmitters controlling blood pressure in rats."} {"id": "PMID:1263357", "title": "Serotonin antagonism in isolated canine cerebral arteries.", "content": "In helically-cut strips of canine cerebral arteries, the dose-response curve of serotonin was not influenced by 10(-7) M phentolamine but was slightly moved to the right and downward at 10(-6) M. The contractile response to serotonin was unaffected by cocaine (3 X 10(-6)M), atropine (10(-6) M) and propranolol (10(-6) M). The addition of lysergic acid diethylamide (LSD), ergotamine and methysergide caused a dose-dependent contraction. Treatment with LSD (10(-9) and 10(-8) M), ergotamine (10(-10) to 10(-8) M) and methysergide (10(-8) to 10(-6) M) shifted the dose-response curve of serotonin to the right and downward in a dose-dependent manner. The inhibitory effect of methysergide was reversed by washing, while that of ergotamine was not reversed. Apparent pA2 values of LSD, ergotamine and methysergide were 9.17, 9.63 and 7.92, respectively. Contractile responses to 20 mM K+ were not significantly influenced by these blocking agents even in the highest concentrations used. It may be concluded that an alpha-adrenergic mechanism is not involved in the genesis of serotonin-induced contractions and that serotonin acts directly on serotonergic receptors in canine cerebral arteries.", "contents": "Serotonin antagonism in isolated canine cerebral arteries. In helically-cut strips of canine cerebral arteries, the dose-response curve of serotonin was not influenced by 10(-7) M phentolamine but was slightly moved to the right and downward at 10(-6) M. The contractile response to serotonin was unaffected by cocaine (3 X 10(-6)M), atropine (10(-6) M) and propranolol (10(-6) M). The addition of lysergic acid diethylamide (LSD), ergotamine and methysergide caused a dose-dependent contraction. Treatment with LSD (10(-9) and 10(-8) M), ergotamine (10(-10) to 10(-8) M) and methysergide (10(-8) to 10(-6) M) shifted the dose-response curve of serotonin to the right and downward in a dose-dependent manner. The inhibitory effect of methysergide was reversed by washing, while that of ergotamine was not reversed. Apparent pA2 values of LSD, ergotamine and methysergide were 9.17, 9.63 and 7.92, respectively. Contractile responses to 20 mM K+ were not significantly influenced by these blocking agents even in the highest concentrations used. It may be concluded that an alpha-adrenergic mechanism is not involved in the genesis of serotonin-induced contractions and that serotonin acts directly on serotonergic receptors in canine cerebral arteries."} {"id": "PMID:1263358", "title": "Effects of 5-hydroxytryptamine and morphine on the stomach motility in situ.", "content": "The effects of 5-hydroxytryptamine and morphine on the stomach motility were determined in in situ experiments. 5-Hydroxytryptamine and morphine inhibited stomach motility of unanaesthetized cats but did produce a slight contraction of the stomach of anaesthetized cats. In unanaesthetized rabbits, 5-hydroxytryptamine caused a contraction, followed by an inhibition of motility, and morphine depressed motility. The 5-hydroxytryptamine-induced contraction is a direct action on smooth muscle and the inhibition of spontaneous movement due to 5-hydroxytryptamine may be, in part, mediated through catecholamine-release and in part, result from paralysis of the receptors for 5-hydroxytryptamine in the cholinergic nerves in the stomach. In anaesthetized rabbits, 5-hydroxytryptamine produced contraction and morphine had no effect. In unanaesthetized guinea pigs, 5-hydroxytryptamine caused a contraction and morphine abolished spontaneous movement of the stomach. In anaestetized guinea-pigs, 5-hydroxytryptamine caused contraction and morphine produced no effect. The 5-hydroxytryptamine-induced contraction of the guinea pig stomach is indirect. From these results it is concluded that the differences in the modes of actions of 5-hydroxytryptamine and morphine on gastric motility are related to differences in species and experimental conditions such as anaesthesia.", "contents": "Effects of 5-hydroxytryptamine and morphine on the stomach motility in situ. The effects of 5-hydroxytryptamine and morphine on the stomach motility were determined in in situ experiments. 5-Hydroxytryptamine and morphine inhibited stomach motility of unanaesthetized cats but did produce a slight contraction of the stomach of anaesthetized cats. In unanaesthetized rabbits, 5-hydroxytryptamine caused a contraction, followed by an inhibition of motility, and morphine depressed motility. The 5-hydroxytryptamine-induced contraction is a direct action on smooth muscle and the inhibition of spontaneous movement due to 5-hydroxytryptamine may be, in part, mediated through catecholamine-release and in part, result from paralysis of the receptors for 5-hydroxytryptamine in the cholinergic nerves in the stomach. In anaesthetized rabbits, 5-hydroxytryptamine produced contraction and morphine had no effect. In unanaesthetized guinea pigs, 5-hydroxytryptamine caused a contraction and morphine abolished spontaneous movement of the stomach. In anaestetized guinea-pigs, 5-hydroxytryptamine caused contraction and morphine produced no effect. The 5-hydroxytryptamine-induced contraction of the guinea pig stomach is indirect. From these results it is concluded that the differences in the modes of actions of 5-hydroxytryptamine and morphine on gastric motility are related to differences in species and experimental conditions such as anaesthesia."} {"id": "PMID:1263359", "title": "\"Calcium-induced release of calcium\" in rectal smooth muscle of mice.", "content": "Contractile responses to K, ACh, Ba and exogenous Ca of rectal strips from mice were recorded isotonically. These responses consisted of phasic contraction and subsequent tonic contraction. In Ca-depleted preparations exposed to Ca-free bath medium, the contractions by K and ACh disappeared but the contraction by Ba remained constant. This residual contraction by Ba is presumably due to a direct stimulation of Ba to contractile elements of muscle. Metabolic inhibitors (anoxia and DNP) abolished tonic contraction without affecting phasic contraction by exogenous Ca. In Ca-free bath medium, tonic contraction by exogenous Ca immediately disappeared whereas phasic contraction gradually decreased and about 3 hr later remained constant in parallel with the occurrence of residual contraction by Ba. After pretreatment with the removal of Na from bath medium, which produced Ca-release action, phasic contractions by exogenous Ca in Ca-free bath medium were depressed like those by K, ACh and Ba. These results suggest that the phasic contraction by exogenous Ca is produced mainly by release of Ca and partly by influx of Ca. Thus, it is suggested that the same mechanism of Ca-induced release of Ca from the storage sited as described in skeletal muscle is also operating in rectal smooth muscle of mice.", "contents": "\"Calcium-induced release of calcium\" in rectal smooth muscle of mice. Contractile responses to K, ACh, Ba and exogenous Ca of rectal strips from mice were recorded isotonically. These responses consisted of phasic contraction and subsequent tonic contraction. In Ca-depleted preparations exposed to Ca-free bath medium, the contractions by K and ACh disappeared but the contraction by Ba remained constant. This residual contraction by Ba is presumably due to a direct stimulation of Ba to contractile elements of muscle. Metabolic inhibitors (anoxia and DNP) abolished tonic contraction without affecting phasic contraction by exogenous Ca. In Ca-free bath medium, tonic contraction by exogenous Ca immediately disappeared whereas phasic contraction gradually decreased and about 3 hr later remained constant in parallel with the occurrence of residual contraction by Ba. After pretreatment with the removal of Na from bath medium, which produced Ca-release action, phasic contractions by exogenous Ca in Ca-free bath medium were depressed like those by K, ACh and Ba. These results suggest that the phasic contraction by exogenous Ca is produced mainly by release of Ca and partly by influx of Ca. Thus, it is suggested that the same mechanism of Ca-induced release of Ca from the storage sited as described in skeletal muscle is also operating in rectal smooth muscle of mice."} {"id": "PMID:1263402", "title": "[The effect of indomethacin on basal and stimulated plasma renin activity in normal subjects (author's transl)].", "content": "The influence of indomethacin, a potent inhibitor of prostaglandin synthesis, on basal and stimulated plasma renin activities in normal human subjects was determined. Stimulation of the renin activity was achieved by orthostasis or by furosemide. Indomethacin led to a considerable decrease of both basal and stimulated plasma renin activity in chronic and acute experiments. Our experiments provide no evidence that major changes in the sodium balance are responsible for the effects observed. It is concluded that some antagonistic function of the renin angiotensin system and prostaglandins seems probable. These antagonistic actions might play a role in the regulation of the kidney circulation or the arterial blood pressure.", "contents": "[The effect of indomethacin on basal and stimulated plasma renin activity in normal subjects (author's transl)]. The influence of indomethacin, a potent inhibitor of prostaglandin synthesis, on basal and stimulated plasma renin activities in normal human subjects was determined. Stimulation of the renin activity was achieved by orthostasis or by furosemide. Indomethacin led to a considerable decrease of both basal and stimulated plasma renin activity in chronic and acute experiments. Our experiments provide no evidence that major changes in the sodium balance are responsible for the effects observed. It is concluded that some antagonistic function of the renin angiotensin system and prostaglandins seems probable. These antagonistic actions might play a role in the regulation of the kidney circulation or the arterial blood pressure."} {"id": "PMID:1263403", "title": "[The effect of clonidine on renin-release (author's transl)].", "content": "In patients with primary hypertension, intravenous administration of 150 mug Clonidin caused a decrease in arterial pressure, renin activity, RPF, GFR and electrolyte excretion. Activation of intracerebral adrenergic alpha-receptors and diminished sympathetic outflow seem to be responsible for the decrease of renin release.", "contents": "[The effect of clonidine on renin-release (author's transl)]. In patients with primary hypertension, intravenous administration of 150 mug Clonidin caused a decrease in arterial pressure, renin activity, RPF, GFR and electrolyte excretion. Activation of intracerebral adrenergic alpha-receptors and diminished sympathetic outflow seem to be responsible for the decrease of renin release."} {"id": "PMID:1263404", "title": "[The treatment of excessive arterial hypertension by a permanent cardiac pacemaker system: a case report concerning the possibility to influence the disturbed harmonization between the heart and the arterial system (author's transl)].", "content": "In a 63 year old female patient with a history of longstanding arterial hypertension the implantation of a permanent cardiac pacemaker system resulted in a drastic reduction of the elevated blood pressure values, allowing to reduce the formerly necessary high dosage of antihypertensive drugs. It can be assumed that in the case presented the insertion of the permanent pacemaker leads to several hemodynamic changes: firstly, the heart rate is elevated slightly, secondly, the course of the ejection of the stroke volume is changed and consequently the contour of the pulse wave. Especially the latter factor may have an influence on various regulating mechanisms of the circulatory system and thereby on the lowering of the arterial blood pressure and the consecutive reduction of the hypertrophy of the left ventricle. Most probably the baroreceptor reflex system may be of additional great importance. In addition the \"desynchronization\" of the spread of excitation by the cardiac pacer might be assumed to change the action of the heart in the beginning of the ejection phase into a \"softer\" way of pumping. The alteration of a rather \"rigid\" pump (during normal excitation) into a \"soft\" pump (during desynchronized excitation) thus may lead to a lowering of the arterial pressure a) by decreasing the speed of ejection of the stroke volume and b) by improving the matching between the heart and the arterial \"Windkessel\".", "contents": "[The treatment of excessive arterial hypertension by a permanent cardiac pacemaker system: a case report concerning the possibility to influence the disturbed harmonization between the heart and the arterial system (author's transl)]. In a 63 year old female patient with a history of longstanding arterial hypertension the implantation of a permanent cardiac pacemaker system resulted in a drastic reduction of the elevated blood pressure values, allowing to reduce the formerly necessary high dosage of antihypertensive drugs. It can be assumed that in the case presented the insertion of the permanent pacemaker leads to several hemodynamic changes: firstly, the heart rate is elevated slightly, secondly, the course of the ejection of the stroke volume is changed and consequently the contour of the pulse wave. Especially the latter factor may have an influence on various regulating mechanisms of the circulatory system and thereby on the lowering of the arterial blood pressure and the consecutive reduction of the hypertrophy of the left ventricle. Most probably the baroreceptor reflex system may be of additional great importance. In addition the \"desynchronization\" of the spread of excitation by the cardiac pacer might be assumed to change the action of the heart in the beginning of the ejection phase into a \"softer\" way of pumping. The alteration of a rather \"rigid\" pump (during normal excitation) into a \"soft\" pump (during desynchronized excitation) thus may lead to a lowering of the arterial pressure a) by decreasing the speed of ejection of the stroke volume and b) by improving the matching between the heart and the arterial \"Windkessel\"."} {"id": "PMID:1263405", "title": "[Somatostatin -- a review (author's transl)].", "content": "Somatostatin, a peptide isolated from ovine hypothalami, prevents growth hormone secretion in vivo and in vitro. Moreover, somatostatin interferes with the secretion of various other hormones: TSH insulin, glucagon, gastrin, VIP and GIP. Under certain conditions a blunting effect on the secretion of prolactin and ACTH can be demonstrated.", "contents": "[Somatostatin -- a review (author's transl)]. Somatostatin, a peptide isolated from ovine hypothalami, prevents growth hormone secretion in vivo and in vitro. Moreover, somatostatin interferes with the secretion of various other hormones: TSH insulin, glucagon, gastrin, VIP and GIP. Under certain conditions a blunting effect on the secretion of prolactin and ACTH can be demonstrated."} {"id": "PMID:1263406", "title": "Effects of free fatty acids on electrophysiological properties of ventricular myocardium.", "content": "Several metabolic factors have been regarded as a cause of ventricular tachyarrhythmias in cardiac ischemia, i.e. hypoxia, acidosis, intracellular potassium loss, local catecholamine release as well as an increased catecholamine concentration and an evaluation of serum free fatty acids. The arrhythmogenic properties of anoxia and hypoxic acidosis, catecholamines as well as potassium depletion are well known. However, the relationship between elevated free fatty acids concentration and the occurrence of ventricular arrhythmias remain obscure. The micro-electrode technique was applied to examine the electrophysiological effects of free fatty acids in papillary heart muscle fibres. Both linoleate and palmitate cause a concentration-dependent decrease of action potential duration and a corresponding shortening of the functional refractory period in the presence of sufficient oxygen supply. The results suggest that a high concentration of free fatty acids may play an additional role in the genesis of ventricular tachyarrhythmias in cardiac ischemia.", "contents": "Effects of free fatty acids on electrophysiological properties of ventricular myocardium. Several metabolic factors have been regarded as a cause of ventricular tachyarrhythmias in cardiac ischemia, i.e. hypoxia, acidosis, intracellular potassium loss, local catecholamine release as well as an increased catecholamine concentration and an evaluation of serum free fatty acids. The arrhythmogenic properties of anoxia and hypoxic acidosis, catecholamines as well as potassium depletion are well known. However, the relationship between elevated free fatty acids concentration and the occurrence of ventricular arrhythmias remain obscure. The micro-electrode technique was applied to examine the electrophysiological effects of free fatty acids in papillary heart muscle fibres. Both linoleate and palmitate cause a concentration-dependent decrease of action potential duration and a corresponding shortening of the functional refractory period in the presence of sufficient oxygen supply. The results suggest that a high concentration of free fatty acids may play an additional role in the genesis of ventricular tachyarrhythmias in cardiac ischemia."} {"id": "PMID:1263407", "title": "[Pulmonary gas exchange after myocardial infarction in the late period of recovery. I. Investigation at rest].", "content": "In the late period of recovery after myocardial infarction (13-25 months p. infarctum) lung function of 23 patients was examined at rest. Spirometric values and parameters of pulmonary gas exchange showed alterations caused by pathological left ventricular function. Arterial Po2 was slightly decreased (chi=74.5 +/- 5.9 Torr), AaDo2 (chi=33.6 +/- 7.7 Torr) and aADco2 (chi=8.6 +/- 3.7 Torr) were increased. Pathological changes of arterial Pco2 (chi=40.6 +/- 2.5 Torr) were not observed. Mixed venous Po2 and cardiac output in 9 patients suggested cardiac failure. In a number of pulmonary parameters measured at rest correlations could prove a dependence on the patients physical work capacity.", "contents": "[Pulmonary gas exchange after myocardial infarction in the late period of recovery. I. Investigation at rest]. In the late period of recovery after myocardial infarction (13-25 months p. infarctum) lung function of 23 patients was examined at rest. Spirometric values and parameters of pulmonary gas exchange showed alterations caused by pathological left ventricular function. Arterial Po2 was slightly decreased (chi=74.5 +/- 5.9 Torr), AaDo2 (chi=33.6 +/- 7.7 Torr) and aADco2 (chi=8.6 +/- 3.7 Torr) were increased. Pathological changes of arterial Pco2 (chi=40.6 +/- 2.5 Torr) were not observed. Mixed venous Po2 and cardiac output in 9 patients suggested cardiac failure. In a number of pulmonary parameters measured at rest correlations could prove a dependence on the patients physical work capacity."} {"id": "PMID:1263408", "title": "[Pulmonary gas exchange after myocardial infarction in the late period of recovery. II. Investigations during exercise (author's transl)].", "content": "After myocardial infarction in the late period of recovery (13-25 months p. infarctum) pulmonary gas exchange in 23 patients was measured besides as hemodynamic parameters during exercise. The parameters take a course similar to that of subjects without lung and heart diseases. Arterial blood gas tensions (Pa02, Paco2) remain unchanged compared to resting values. Alveolar ventilation did show no difference in any of the patients. Minute ventilation VE, the various dead spaces, alveolar-arterial gas differences (AaDo2, aADco2) and ventilation-perfusion ratios of the whole lung VA/Q suggest however that these parameters show different courses according to the physical capacity of the patients. As the physical capacity of each patient is due to different cardiac functions taken by cardiac output and mixed venous blood gas tensions alterations of pulmonary gas exchange seemed to be dependent on the respective left ventricular function of the heart. Of the twenty-three patients, twelve with cardiac failure under exercise showed the most pronounced alterations in pulmonary gas exchange. Therefore, the different physical work capacity of the patients are determined only by cardiac function. No limitation of the productivity due to impeded lung function could be proved.", "contents": "[Pulmonary gas exchange after myocardial infarction in the late period of recovery. II. Investigations during exercise (author's transl)]. After myocardial infarction in the late period of recovery (13-25 months p. infarctum) pulmonary gas exchange in 23 patients was measured besides as hemodynamic parameters during exercise. The parameters take a course similar to that of subjects without lung and heart diseases. Arterial blood gas tensions (Pa02, Paco2) remain unchanged compared to resting values. Alveolar ventilation did show no difference in any of the patients. Minute ventilation VE, the various dead spaces, alveolar-arterial gas differences (AaDo2, aADco2) and ventilation-perfusion ratios of the whole lung VA/Q suggest however that these parameters show different courses according to the physical capacity of the patients. As the physical capacity of each patient is due to different cardiac functions taken by cardiac output and mixed venous blood gas tensions alterations of pulmonary gas exchange seemed to be dependent on the respective left ventricular function of the heart. Of the twenty-three patients, twelve with cardiac failure under exercise showed the most pronounced alterations in pulmonary gas exchange. Therefore, the different physical work capacity of the patients are determined only by cardiac function. No limitation of the productivity due to impeded lung function could be proved."} {"id": "PMID:1263409", "title": "[Experimental studies to the teratogen effects of virus-induced fever (author's transl)].", "content": "Fever was induced in pregnant rabbits at the 9th day of gestation by injection of a heat inactivated virus which had not lost its pyrogenic activity. The mother rabbits were killed on the 29th day of pregnancy, the fetuses taken out and the uteri examined for resorptions. The fetuses were inspected for organ malformations macroscopically and for skeleten malformations microscopically. The results were compared with those of control animals. The rise of temperature up to a maximum 2,1 degrees C above normal temperature resulted in no higher resorption and malformation rate.", "contents": "[Experimental studies to the teratogen effects of virus-induced fever (author's transl)]. Fever was induced in pregnant rabbits at the 9th day of gestation by injection of a heat inactivated virus which had not lost its pyrogenic activity. The mother rabbits were killed on the 29th day of pregnancy, the fetuses taken out and the uteri examined for resorptions. The fetuses were inspected for organ malformations macroscopically and for skeleten malformations microscopically. The results were compared with those of control animals. The rise of temperature up to a maximum 2,1 degrees C above normal temperature resulted in no higher resorption and malformation rate."} {"id": "PMID:1263410", "title": "[State of vascular regulation and regional hemodynamics in the crew of \"Soiuz-12\" and \"Soiuz-13\" spaceships before and after flight].", "content": "Postflight rheographic examinations carried out at rest and during postural tests showed noticeable changes in the vascular regulation and significant blood redistribution. On the recovery day there were no signs of the intracranical venous congestion to weightlessness. The tone of cerebral vessels, however, increased to prevent the development of cerebral venous congestions during the antiorthostatic test. This may be a result of weightlessness adaptation. These cerebral hemodynamic reactions were more pronounced in the crewmembers who made an 8-day flight than in those who made a two-day flight, i. e. in the cosmonauts who returned to Earth after weightlessness adaptation.", "contents": "[State of vascular regulation and regional hemodynamics in the crew of \"Soiuz-12\" and \"Soiuz-13\" spaceships before and after flight]. Postflight rheographic examinations carried out at rest and during postural tests showed noticeable changes in the vascular regulation and significant blood redistribution. On the recovery day there were no signs of the intracranical venous congestion to weightlessness. The tone of cerebral vessels, however, increased to prevent the development of cerebral venous congestions during the antiorthostatic test. This may be a result of weightlessness adaptation. These cerebral hemodynamic reactions were more pronounced in the crewmembers who made an 8-day flight than in those who made a two-day flight, i. e. in the cosmonauts who returned to Earth after weightlessness adaptation."} {"id": "PMID:1263412", "title": "[Model of the thermoregulation physiological system].", "content": "A mathematical model of the thermoregulation system that allows two steady-state states (the state of rest and autooscillation regimen) has been developed. Certain relationships required for a quantitative description of thermoregulation system are presented.", "contents": "[Model of the thermoregulation physiological system]. A mathematical model of the thermoregulation system that allows two steady-state states (the state of rest and autooscillation regimen) has been developed. Certain relationships required for a quantitative description of thermoregulation system are presented."} {"id": "PMID:1263413", "title": "[Study of the flight work capacity of pilots during simulated motion sickness].", "content": "With the aid of a modified procedure of reading instrumental indications of an aircraft the professional performance of pilots was studied during simulated motion sickness. A ball system was developed to assess the results of reading the instrumental indications. After five exposures to double rotation statokinetically stable pilots developed a latent form and statokinetically unstable pilots developed an overt form of motion sickness. The latent form of motion sickness manifested itself in deteriorated professional performance. The overt form of motion sickness was preceded by a decline of professional performance.", "contents": "[Study of the flight work capacity of pilots during simulated motion sickness]. With the aid of a modified procedure of reading instrumental indications of an aircraft the professional performance of pilots was studied during simulated motion sickness. A ball system was developed to assess the results of reading the instrumental indications. After five exposures to double rotation statokinetically stable pilots developed a latent form and statokinetically unstable pilots developed an overt form of motion sickness. The latent form of motion sickness manifested itself in deteriorated professional performance. The overt form of motion sickness was preceded by a decline of professional performance."} {"id": "PMID:1263414", "title": "[Effect of hyperoxia on indices of external respiration, cardiovascular system and blood gas composition].", "content": "In eight healthy male test subjects, aged 19-32, pulmonary ventilation, oxygen consumption, partial pressure of oxygen and carbon dioxide in the alveolar air, arterial and venous blood, ECG, arterial pressure and skin microcirculation were measured during 20 min inhalation of 70% oxygen. In hyperoxic subjects cardiac output remained unaltered, respiration rate decreased, respiration volume increased, alveolar-arterial and arterio-venous difference of PO2 increased, the difference between the actual and expected Q-T slightly decreased, capillary cirulation changed indicating a spactic reaction of peripheral vessels. At the same time oxygen consumption, ventilation equivalent, coefficient of oxygen utilization, partial pressure of carbon dioxide in the alveolar air, arterial and venous blood, heart rate, maximum arterial pressure remained essentially unchanged.", "contents": "[Effect of hyperoxia on indices of external respiration, cardiovascular system and blood gas composition]. In eight healthy male test subjects, aged 19-32, pulmonary ventilation, oxygen consumption, partial pressure of oxygen and carbon dioxide in the alveolar air, arterial and venous blood, ECG, arterial pressure and skin microcirculation were measured during 20 min inhalation of 70% oxygen. In hyperoxic subjects cardiac output remained unaltered, respiration rate decreased, respiration volume increased, alveolar-arterial and arterio-venous difference of PO2 increased, the difference between the actual and expected Q-T slightly decreased, capillary cirulation changed indicating a spactic reaction of peripheral vessels. At the same time oxygen consumption, ventilation equivalent, coefficient of oxygen utilization, partial pressure of carbon dioxide in the alveolar air, arterial and venous blood, heart rate, maximum arterial pressure remained essentially unchanged."} {"id": "PMID:1263415", "title": "[Possible methods of evaluating the work capacity of ship operators].", "content": "By identifying correlation between physiological changes that develop in work and professional errors of ship operators the complex of informative parameters to be used in assaying ther performance has been determined. The complex includes: latent period of a complex sensorimotor response with a choice, critical frequence of fusion of light oscillations, heart rate, tolerance to static force, pulse arterial pressure and index of a two-minute step-test. With the aid of the complex of clinical, physiological and psychophysiological methods it has been shown that indirect indices of performance of operators in long voyages deteriorate two or three weeks earlier than its direct signs. It has been found that the operator's performance can in principle be quantified. It can be done by taking into consideration changes in the informative indices during a specific operation and contribution of each of them to the integrative evaluation of the operator's performance.", "contents": "[Possible methods of evaluating the work capacity of ship operators]. By identifying correlation between physiological changes that develop in work and professional errors of ship operators the complex of informative parameters to be used in assaying ther performance has been determined. The complex includes: latent period of a complex sensorimotor response with a choice, critical frequence of fusion of light oscillations, heart rate, tolerance to static force, pulse arterial pressure and index of a two-minute step-test. With the aid of the complex of clinical, physiological and psychophysiological methods it has been shown that indirect indices of performance of operators in long voyages deteriorate two or three weeks earlier than its direct signs. It has been found that the operator's performance can in principle be quantified. It can be done by taking into consideration changes in the informative indices during a specific operation and contribution of each of them to the integrative evaluation of the operator's performance."} {"id": "PMID:1263417", "title": "[Results of mammalian cell culture exposure on artificial earth satellites].", "content": "The paper presents the results of an exposure of cells of the Syrian hamster strain VNK-21 to space flight effects. In contrast to the cell culture kept in a thermostat at 29 degrees C, the cell culture that was maintained in thermally uncontrolled conditions developed noticeable structural and physiological changes induced by suboptimal temperatures. It was concluded that a 6-day exposure to weightlessness exerted no adverse effect on mammalian cells in vitro and produced no stable structural or physiological changes. Some changes that were detected in the cell culture--faster ageing, stable tendency to an increase of the number of cells with enlarged nuclei, an increase of the mitotic index at an early stage of cultivation--need further investigation.", "contents": "[Results of mammalian cell culture exposure on artificial earth satellites]. The paper presents the results of an exposure of cells of the Syrian hamster strain VNK-21 to space flight effects. In contrast to the cell culture kept in a thermostat at 29 degrees C, the cell culture that was maintained in thermally uncontrolled conditions developed noticeable structural and physiological changes induced by suboptimal temperatures. It was concluded that a 6-day exposure to weightlessness exerted no adverse effect on mammalian cells in vitro and produced no stable structural or physiological changes. Some changes that were detected in the cell culture--faster ageing, stable tendency to an increase of the number of cells with enlarged nuclei, an increase of the mitotic index at an early stage of cultivation--need further investigation."} {"id": "PMID:1263416", "title": "[Study of the rate of acoustic reception of radiotelegraphic signals during the psychological selection of candidates for flight training].", "content": "Psychophysiological characteristics and results of training of cadets of pilot schools who had excellent and bad marks in the reception of radiotelegraph signals by ear were examined. The cadets who had excellent marks in that subject also had better marks in the velocity of the skill development, attention parameters and results of flying training. They also showed a higher value of the EEG alpha-rhythm. The procedure of measuring the capacity of candidates to develop a complex sensomotor skill in the reception of radiotelegraph signals by ear may be well used in the psychophysiological selection of pilot-cadets.", "contents": "[Study of the rate of acoustic reception of radiotelegraphic signals during the psychological selection of candidates for flight training]. Psychophysiological characteristics and results of training of cadets of pilot schools who had excellent and bad marks in the reception of radiotelegraph signals by ear were examined. The cadets who had excellent marks in that subject also had better marks in the velocity of the skill development, attention parameters and results of flying training. They also showed a higher value of the EEG alpha-rhythm. The procedure of measuring the capacity of candidates to develop a complex sensomotor skill in the reception of radiotelegraph signals by ear may be well used in the psychophysiological selection of pilot-cadets."} {"id": "PMID:1263418", "title": "[Effect on mitotic activity of prolonged exposure to constant and alternating 1000 oersted magnetic fields].", "content": "During a prolonged (15 days) exposure to a constant magnetic field of 1000 oersted two-phasic changes in the mitotic index of the corneal epithelium and bone marrow were noted. The initial decrease of the index was replaced with its recovery and hyperregeneration. The cell count of the tissues varied insignificantly and rapidly returned to normal when the field was switched off. The every day change in the field direction with respect to the body position of the test animals induced no increase in the inhibition of the mitotic activity; however, the effectiveness of adaptive processes declined noticeably. These exposures did not induce chromosome aberrations in the cells of the tested tissues.", "contents": "[Effect on mitotic activity of prolonged exposure to constant and alternating 1000 oersted magnetic fields]. During a prolonged (15 days) exposure to a constant magnetic field of 1000 oersted two-phasic changes in the mitotic index of the corneal epithelium and bone marrow were noted. The initial decrease of the index was replaced with its recovery and hyperregeneration. The cell count of the tissues varied insignificantly and rapidly returned to normal when the field was switched off. The every day change in the field direction with respect to the body position of the test animals induced no increase in the inhibition of the mitotic activity; however, the effectiveness of adaptive processes declined noticeably. These exposures did not induce chromosome aberrations in the cells of the tested tissues."} {"id": "PMID:1263420", "title": "[Clinical and physiological studies of flight personnel with 1st stage hypertensive disease].", "content": "An examination of the functional state of the cardiovascular system of 30 pilots with hypertension of the I stage showed that the parameters expressing an increase of the blood ejected to the vascular bed were the most informative hemodynamic and polycardiographic values. It was found that the stroke volume, cardiac output, volume velocity of the ejection, power of the left ventricle, energy expenditure per I 1 of cardiac output and time of the isometric contraction phase increased. The interactions of the cardiac output and peripheral resistance made it possible to distinguish hemodynamic modifications of the hypertensive disease: cardiac-increased cardiac output (15 pilots), vascular--increased peripheral resitance (11 pilots) and mixed--simultaneous increase of both parameters (4 pilots). The identification of the modification is important for proper treatment and expertise.", "contents": "[Clinical and physiological studies of flight personnel with 1st stage hypertensive disease]. An examination of the functional state of the cardiovascular system of 30 pilots with hypertension of the I stage showed that the parameters expressing an increase of the blood ejected to the vascular bed were the most informative hemodynamic and polycardiographic values. It was found that the stroke volume, cardiac output, volume velocity of the ejection, power of the left ventricle, energy expenditure per I 1 of cardiac output and time of the isometric contraction phase increased. The interactions of the cardiac output and peripheral resistance made it possible to distinguish hemodynamic modifications of the hypertensive disease: cardiac-increased cardiac output (15 pilots), vascular--increased peripheral resitance (11 pilots) and mixed--simultaneous increase of both parameters (4 pilots). The identification of the modification is important for proper treatment and expertise."} {"id": "PMID:1263428", "title": "Changes in rat milk quantity and quality due to variations in litter size and high ambient temperature.", "content": "The effects of variations in suckling stimulus (changes in letter size) and exposure to high ambient temperatures on the quality and quantity of rat's milk and mammary tissue structure were determined. By increasing the number of suckling pups per dam, it was found that the amount of milk produced by the animals was proportionally increased, as each pup was able to drink the same amount of milk per day. With more than 6 pups per litter, the quality of the milk was not significanly changed. Smaller letters led to changes in the amount of milk suckled per milking and to considerable changes in the content of the milk. Exposure to high ambient temperatures, although for only 8 hr per day, drastically affected the amount of milk produced by the lactating rat as well as the quality of the milk produced. Microscopic examination of mammary tissue revealed changes in the alveolar area and height of the alveolar cells as the suckling stimulus varied. After heat exposure the gland changed to one of diminished synthesizing capability. It was concluded that 10-pup litters are the optimal litter size for research concerning rat milk, and the exposure to high ambient temperatures affects the milk yield by directly affecting the alveolae.", "contents": "Changes in rat milk quantity and quality due to variations in litter size and high ambient temperature. The effects of variations in suckling stimulus (changes in letter size) and exposure to high ambient temperatures on the quality and quantity of rat's milk and mammary tissue structure were determined. By increasing the number of suckling pups per dam, it was found that the amount of milk produced by the animals was proportionally increased, as each pup was able to drink the same amount of milk per day. With more than 6 pups per litter, the quality of the milk was not significanly changed. Smaller letters led to changes in the amount of milk suckled per milking and to considerable changes in the content of the milk. Exposure to high ambient temperatures, although for only 8 hr per day, drastically affected the amount of milk produced by the lactating rat as well as the quality of the milk produced. Microscopic examination of mammary tissue revealed changes in the alveolar area and height of the alveolar cells as the suckling stimulus varied. After heat exposure the gland changed to one of diminished synthesizing capability. It was concluded that 10-pup litters are the optimal litter size for research concerning rat milk, and the exposure to high ambient temperatures affects the milk yield by directly affecting the alveolae."} {"id": "PMID:1263429", "title": "Increased fertility in rhesus monkeys by breeding after the preovulatory LH surge.", "content": "Fertility in a rhesus monkey breeding colony was significantly increased by caging females with males immediately after detection of the preovulatory luteinizing hormone (LH) surge. LH was measured in daily serum samples by a rapid (24-hr) radioimmunoassay which used iodinated ovine LK as tracer and an antiserum to human LH.", "contents": "Increased fertility in rhesus monkeys by breeding after the preovulatory LH surge. Fertility in a rhesus monkey breeding colony was significantly increased by caging females with males immediately after detection of the preovulatory luteinizing hormone (LH) surge. LH was measured in daily serum samples by a rapid (24-hr) radioimmunoassay which used iodinated ovine LK as tracer and an antiserum to human LH."} {"id": "PMID:1263419", "title": "[Reactions of granulation tissue fibroblasts in regenerating skin to chronic hypoxia].", "content": "An investigation of the effect of chronic hypoxia on fibroblasts of the granulation tissue of a regenerating wound showed that an appreciable portion of fibroblasts degenerated and died. Some of the cells retained their capability to synthesize collagen but its excretion outside the cell was disordered. It also demonstrated an inhibition of fibrillogenesis and thus delayed regeneration of an experimental lesion.", "contents": "[Reactions of granulation tissue fibroblasts in regenerating skin to chronic hypoxia]. An investigation of the effect of chronic hypoxia on fibroblasts of the granulation tissue of a regenerating wound showed that an appreciable portion of fibroblasts degenerated and died. Some of the cells retained their capability to synthesize collagen but its excretion outside the cell was disordered. It also demonstrated an inhibition of fibrillogenesis and thus delayed regeneration of an experimental lesion."} {"id": "PMID:1263431", "title": "T-strain mycoplasma in the chimpanzee.", "content": "Specimens from 4 chimpanzees were cultured for T-strain mycoplasma and Mycoplasma hominis. T-strain mycoplasmas were recovered from the genital tract and throat of a male and the genital tract of his female cagemate; neither had clinical evidence of infection. Two other male chimpanzees were culturally negative for T-strain mycoplasmas. M hominis was not isolated from any of the animals. The chimpanzee may serve as a suitable experimental model for studying the role of T-strain mycoplasmas in human urethritis and reproductive failure.", "contents": "T-strain mycoplasma in the chimpanzee. Specimens from 4 chimpanzees were cultured for T-strain mycoplasma and Mycoplasma hominis. T-strain mycoplasmas were recovered from the genital tract and throat of a male and the genital tract of his female cagemate; neither had clinical evidence of infection. Two other male chimpanzees were culturally negative for T-strain mycoplasmas. M hominis was not isolated from any of the animals. The chimpanzee may serve as a suitable experimental model for studying the role of T-strain mycoplasmas in human urethritis and reproductive failure."} {"id": "PMID:1263432", "title": "Disseminated staphylococcal disease in laboratory rabbits (Oryctolagus cuniculus).", "content": "The pathologic findings in 13 cases of staphylococcal disease in New Zealand white rabbits were described. Subcutaneous abscesses and embolic pyemic abscesses in kidney, heart, brain, and lung were found. Conjunctivitis, rhinitis, otitis media, and fibrinous pneumonia also occurred. One rabbit had a valvular endocarditis. Staphylococcus aureus, coagulase-positive, and fermenting mannitol were isolated from the lesions described. Staphylococcal disease was diagnosed in 13 of the 171 (7.6%) rabbits necropsied during a 3-yr period. Disseminated staphylococcal lesions were observed only in rabbits during this time.", "contents": "Disseminated staphylococcal disease in laboratory rabbits (Oryctolagus cuniculus). The pathologic findings in 13 cases of staphylococcal disease in New Zealand white rabbits were described. Subcutaneous abscesses and embolic pyemic abscesses in kidney, heart, brain, and lung were found. Conjunctivitis, rhinitis, otitis media, and fibrinous pneumonia also occurred. One rabbit had a valvular endocarditis. Staphylococcus aureus, coagulase-positive, and fermenting mannitol were isolated from the lesions described. Staphylococcal disease was diagnosed in 13 of the 171 (7.6%) rabbits necropsied during a 3-yr period. Disseminated staphylococcal lesions were observed only in rabbits during this time."} {"id": "PMID:1263433", "title": "An autoclavable intensive care isolator for the adult gnotobiotic dog.", "content": "A lightweight stainless steel isolator which allows 3 investigators simultaneous access to an adult gnotobiotic dog for the purpose of rendering intensive care was designed and constructed. This isolator is 54'' high X 60'' long X 42'' wide. It has an 18'' diam entry port at 1 end and a pair of gloves mounted beneath a window on each of the other 3 sides. The chamber rests on a 12'' high pallet and is moved about the laboratory by a portable hydraulic platform lift. It can be rapidly cleansed with soap and water and sterilized in a large autoclave. Over the past 2 yr. this intensive care isolator has enabled us to perform a variety of manipulations on the adult gnotobiotic dog in a safe, convenient, and efficient manner.", "contents": "An autoclavable intensive care isolator for the adult gnotobiotic dog. A lightweight stainless steel isolator which allows 3 investigators simultaneous access to an adult gnotobiotic dog for the purpose of rendering intensive care was designed and constructed. This isolator is 54'' high X 60'' long X 42'' wide. It has an 18'' diam entry port at 1 end and a pair of gloves mounted beneath a window on each of the other 3 sides. The chamber rests on a 12'' high pallet and is moved about the laboratory by a portable hydraulic platform lift. It can be rapidly cleansed with soap and water and sterilized in a large autoclave. Over the past 2 yr. this intensive care isolator has enabled us to perform a variety of manipulations on the adult gnotobiotic dog in a safe, convenient, and efficient manner."} {"id": "PMID:1263434", "title": "An improved method for repeated plasmapheresis in the rat.", "content": "An improved method for plasmapheresis in the rat was designed. The rat was anesthetized with ketamine hydrochloride, and venipuncture of the iliac vein was performed with a 21-ga butterfly infusion set with 12'' of flexible tubing. Six ml of blood were drawn into a heparinized syringe and centrifugated. After the plasma was separated, the rbc were reinfused through the phlebotomy apparatus. This procedure was performed on each rat weekly for 10 wk without apparent harm to the animals. There were no changes in total serum protein and albumin, and body weights in most animals remained constant. This method should prove valuable in studies in which long-term plasmapheresis is indicated.", "contents": "An improved method for repeated plasmapheresis in the rat. An improved method for plasmapheresis in the rat was designed. The rat was anesthetized with ketamine hydrochloride, and venipuncture of the iliac vein was performed with a 21-ga butterfly infusion set with 12'' of flexible tubing. Six ml of blood were drawn into a heparinized syringe and centrifugated. After the plasma was separated, the rbc were reinfused through the phlebotomy apparatus. This procedure was performed on each rat weekly for 10 wk without apparent harm to the animals. There were no changes in total serum protein and albumin, and body weights in most animals remained constant. This method should prove valuable in studies in which long-term plasmapheresis is indicated."} {"id": "PMID:1263440", "title": "Cellular aspects of rabbit Masugi nephritis. III. Mesangial changes.", "content": "Lytic disarrangement of mesangial matrix was noted in acute proliferative glomerulonephritis induced in the rabbit by injection of duck nephrotoxic antibody. The severity of the change was variable depending upon dose of the antibody injected. With severe mesangiolysis, mesangial areas were highly obscured by marked hypertrophy and proliferation of mesangial cells along with massive infiltration of monocytes into the loosened mesangium and subendothelial space. In addition, there was random mobilization of the mesangial cells as shown by peripheral interposition and intraluminal projection with capillary subdivision. Glomerular capillaries were thus narrowed and distorted. The ultrastructural hallmark of the proliferated mesangial cells was prominence of the Golgi complex and endoplasmic reticulum which suggested accelerated protein synthesis, most likely for repair of the damaged matrix. In the affected glomeruli, exclusive of those undergoing rapid obliteration due to basement membrane rupture, resolution of the acute inflammatory process occurred within 2 weeks. At this stage, two types of glomerular changes became manifest, consisting of: (1) prominent mesangial stalk thickening and cellularity with occasional peripheral interposition of mesangial cells, and (2) segmental capillary subdivisions due to mesangial bridges built between the original mesangium and peripheral loop. It is suggested that chronic glomerular disease may develop based upon these persistent alterations of the glomerular structure. When a smaller dose of the duck antibody was employed, the process was much less prominent and complete recovery from acute glomerulonephritis took place.", "contents": "Cellular aspects of rabbit Masugi nephritis. III. Mesangial changes. Lytic disarrangement of mesangial matrix was noted in acute proliferative glomerulonephritis induced in the rabbit by injection of duck nephrotoxic antibody. The severity of the change was variable depending upon dose of the antibody injected. With severe mesangiolysis, mesangial areas were highly obscured by marked hypertrophy and proliferation of mesangial cells along with massive infiltration of monocytes into the loosened mesangium and subendothelial space. In addition, there was random mobilization of the mesangial cells as shown by peripheral interposition and intraluminal projection with capillary subdivision. Glomerular capillaries were thus narrowed and distorted. The ultrastructural hallmark of the proliferated mesangial cells was prominence of the Golgi complex and endoplasmic reticulum which suggested accelerated protein synthesis, most likely for repair of the damaged matrix. In the affected glomeruli, exclusive of those undergoing rapid obliteration due to basement membrane rupture, resolution of the acute inflammatory process occurred within 2 weeks. At this stage, two types of glomerular changes became manifest, consisting of: (1) prominent mesangial stalk thickening and cellularity with occasional peripheral interposition of mesangial cells, and (2) segmental capillary subdivisions due to mesangial bridges built between the original mesangium and peripheral loop. It is suggested that chronic glomerular disease may develop based upon these persistent alterations of the glomerular structure. When a smaller dose of the duck antibody was employed, the process was much less prominent and complete recovery from acute glomerulonephritis took place."} {"id": "PMID:1263441", "title": "Protein synthesis in liver injury. Soluble factors of protein synthesis in the cytosol from ischemic rat liver.", "content": "The high speed supernatant (cell sap) obtained from ischemic livers is less efficient than normal in supporting protein synthesis in cell-free systems. Cell saps from ischemic livers contain a reduced amount of transfer-RNA; the transfer of leucine to the specific tRNA is impaired; the incorporation of leucyl-tRNA into protein is reduced, although less than the incorporation of the corresponding amino acid. The binding of aminoacyl-tRNA to ribosomal subunits and exogenous messengers (polyuridylic acid and uridyl-3'-5'-uridyl-3'-5'-guanosine), is less efficient with ischemic than with normal cells sap, thus indicating a defective activity of elongation factor 1. The total amount-and possibly the intracellular distribution-of elongation factor 2 is also altered in ischemic livers. These changes, which are the expression of a multifunctional deficit of ischemic cell sap, are in general correlated with the duration of ischemia and do not seem to appear around the \"point of no return\" of the ischemic liver cells.", "contents": "Protein synthesis in liver injury. Soluble factors of protein synthesis in the cytosol from ischemic rat liver. The high speed supernatant (cell sap) obtained from ischemic livers is less efficient than normal in supporting protein synthesis in cell-free systems. Cell saps from ischemic livers contain a reduced amount of transfer-RNA; the transfer of leucine to the specific tRNA is impaired; the incorporation of leucyl-tRNA into protein is reduced, although less than the incorporation of the corresponding amino acid. The binding of aminoacyl-tRNA to ribosomal subunits and exogenous messengers (polyuridylic acid and uridyl-3'-5'-uridyl-3'-5'-guanosine), is less efficient with ischemic than with normal cells sap, thus indicating a defective activity of elongation factor 1. The total amount-and possibly the intracellular distribution-of elongation factor 2 is also altered in ischemic livers. These changes, which are the expression of a multifunctional deficit of ischemic cell sap, are in general correlated with the duration of ischemia and do not seem to appear around the \"point of no return\" of the ischemic liver cells."} {"id": "PMID:1263442", "title": "Experimental canine atherosclerosis and its prevention. The dietary induction of severe coronary, cerebral, aortic, and iliac atherosclerosis and its prevention by safflower oil.", "content": "Severe atherosclerotic lesions were produced without thyroid suppression in seven out of eight dogs by feeding semisynthetic diets containing 5 per cent cholesterol and 16 per cent hydrogenated coconut oil for 12 to 14 months. Occlusive plaques were located in the coronary arteries and major cerebral arteries as well as in the aorta and iliac vessels. The lesions were characterized by an intense sclerotic reaction to areas of lipid deposition and foam cell accumulation in the intima. The diet induced a rapid elevation of plasma-free and esterfied cholesterol, triglyceride, and phospholipid, and the extent of aortic atherosclerosis was shown to be partially dependent on mean plasma cholesterol concentration. A second group of eight dogs were fed a diet identical with the first except for the replacement of 4 per cent hydrogenated coconut oil by 4 per cent safflower oil. Despite receiving the same amounts of dietary cholesterol and fat, this second group of dogs was completely protected from the atherogenic process. Plasma lipids became only slightly elevated and no induced atherosclerotic lesions were found at autopsy. Circulating thyroid hormone concentrations were similar between the two groups of dogs and the thyroid glands had a normal morphology in both groups.", "contents": "Experimental canine atherosclerosis and its prevention. The dietary induction of severe coronary, cerebral, aortic, and iliac atherosclerosis and its prevention by safflower oil. Severe atherosclerotic lesions were produced without thyroid suppression in seven out of eight dogs by feeding semisynthetic diets containing 5 per cent cholesterol and 16 per cent hydrogenated coconut oil for 12 to 14 months. Occlusive plaques were located in the coronary arteries and major cerebral arteries as well as in the aorta and iliac vessels. The lesions were characterized by an intense sclerotic reaction to areas of lipid deposition and foam cell accumulation in the intima. The diet induced a rapid elevation of plasma-free and esterfied cholesterol, triglyceride, and phospholipid, and the extent of aortic atherosclerosis was shown to be partially dependent on mean plasma cholesterol concentration. A second group of eight dogs were fed a diet identical with the first except for the replacement of 4 per cent hydrogenated coconut oil by 4 per cent safflower oil. Despite receiving the same amounts of dietary cholesterol and fat, this second group of dogs was completely protected from the atherogenic process. Plasma lipids became only slightly elevated and no induced atherosclerotic lesions were found at autopsy. Circulating thyroid hormone concentrations were similar between the two groups of dogs and the thyroid glands had a normal morphology in both groups."} {"id": "PMID:1263443", "title": "A scanning electron microscopic study of the glycerol model of acute renal failure.", "content": "Previous studies have implicated both intrarenal vasconstriction and reduced glomerular permeability in the pathogenesis of acute renal failure. Studies were performed to examine further the role of vasconstriction and glomerular structural abnormalities in this syndrome. Six rats (group I) given angiotensin II (180 ng. per 100 gm. per minute) did not develop acute renal failure (blood urea nitrogen 28.6 mg. per 100 ml. at 24 hours). Twenty-five rats (group II), allowed free access to water and given glycerol intramuscularly (8 ml. per kg.), developed mild acute renal failure (blood urea nitrogen 41.6 mg. per 100 ml. at 24 hours). Ten nondehydrated rats (group III), given both glycerol and angiotensin II, developed a more severe form of acute renal failure (blood urea nitrogen 120.4 mg. per 100 ml. at 24 hours p less than 0.001); this value was not significantly different from that of 14 rats (group IV) dehydrated 24 hours prior to glycerol administration (blood urea nitrogen 137 mg. per 100 ml. at 24 hours).", "contents": "A scanning electron microscopic study of the glycerol model of acute renal failure. Previous studies have implicated both intrarenal vasconstriction and reduced glomerular permeability in the pathogenesis of acute renal failure. Studies were performed to examine further the role of vasconstriction and glomerular structural abnormalities in this syndrome. Six rats (group I) given angiotensin II (180 ng. per 100 gm. per minute) did not develop acute renal failure (blood urea nitrogen 28.6 mg. per 100 ml. at 24 hours). Twenty-five rats (group II), allowed free access to water and given glycerol intramuscularly (8 ml. per kg.), developed mild acute renal failure (blood urea nitrogen 41.6 mg. per 100 ml. at 24 hours). Ten nondehydrated rats (group III), given both glycerol and angiotensin II, developed a more severe form of acute renal failure (blood urea nitrogen 120.4 mg. per 100 ml. at 24 hours p less than 0.001); this value was not significantly different from that of 14 rats (group IV) dehydrated 24 hours prior to glycerol administration (blood urea nitrogen 137 mg. per 100 ml. at 24 hours)."} {"id": "PMID:1263444", "title": "Glomerular permeability to proteins. Effects of hemodynamic factors on the distribution of endogenous immunoglobulin G and exogenous catalase in the rat glomerulus.", "content": "The distribution of endogenous immunoglobulin G (IgG) and exogenous catalase was delineated in the rat glomerulus under normal and abnormal hemodynamic conditions. IgG was identified by an ultrastructural immunoperoxidase technique using antirat IgG Fab fragments conjugated to horseradish peroxidase; catalase was identified by a cytochemical reaction. When superficial glomeruli in anesthetized Munich-Wistar rats were rapidly fixed in situ by dripping glutaraldehyde onto the renal surface, IgG and catalase were largely confined to the glomerular capillary lumen, with only small amounts in the lamina rara interna immediately beneath the endothelial fenestrae, and none deeper in the basement membrane (GBM) or in the urinary space. If cortical tissue was subjected to routine immersion fixation, or if fixation was performed in situ after ligation of the renal artery, IgG and catalase were found throughout the GBM but not in the urinary space. If fixation was performed in situ after ligation of the renal artery and vein (or artery, vein, and ureter), IgG and catalase were found in the GBM and in the urinary space. If blood flow was restored for 10 minutes after 5 minutes of occlusion of the renal artery and vein, the distribution of IgG and catalase returned to that seen during good blood flow, i.e. neither showed significant penetration beyond the endothelial layer. Thus, as was found previously for albumin, glomerular barrier function for IgG and catalase depends upon the maintenance of normal blood flow conditions. We propose that such conditions impose functional restrictions may be mediated by molecular sieving phenomena during normal ultrafiltration across the GBM, perhaps in association with concentration-polarization or charge effects or both. The epithelial slit pores may significantly modulate solute flux across the GBM by controlling the over-all rate of hydrodynamic flow during ultrafiltration.", "contents": "Glomerular permeability to proteins. Effects of hemodynamic factors on the distribution of endogenous immunoglobulin G and exogenous catalase in the rat glomerulus. The distribution of endogenous immunoglobulin G (IgG) and exogenous catalase was delineated in the rat glomerulus under normal and abnormal hemodynamic conditions. IgG was identified by an ultrastructural immunoperoxidase technique using antirat IgG Fab fragments conjugated to horseradish peroxidase; catalase was identified by a cytochemical reaction. When superficial glomeruli in anesthetized Munich-Wistar rats were rapidly fixed in situ by dripping glutaraldehyde onto the renal surface, IgG and catalase were largely confined to the glomerular capillary lumen, with only small amounts in the lamina rara interna immediately beneath the endothelial fenestrae, and none deeper in the basement membrane (GBM) or in the urinary space. If cortical tissue was subjected to routine immersion fixation, or if fixation was performed in situ after ligation of the renal artery, IgG and catalase were found throughout the GBM but not in the urinary space. If fixation was performed in situ after ligation of the renal artery and vein (or artery, vein, and ureter), IgG and catalase were found in the GBM and in the urinary space. If blood flow was restored for 10 minutes after 5 minutes of occlusion of the renal artery and vein, the distribution of IgG and catalase returned to that seen during good blood flow, i.e. neither showed significant penetration beyond the endothelial layer. Thus, as was found previously for albumin, glomerular barrier function for IgG and catalase depends upon the maintenance of normal blood flow conditions. We propose that such conditions impose functional restrictions may be mediated by molecular sieving phenomena during normal ultrafiltration across the GBM, perhaps in association with concentration-polarization or charge effects or both. The epithelial slit pores may significantly modulate solute flux across the GBM by controlling the over-all rate of hydrodynamic flow during ultrafiltration."} {"id": "PMID:1263445", "title": "Transendothelial vesicular transport of protein following compression injury to the spinal cord.", "content": "Routes of vascular leakage resulting in trauma-induced edema have not been clarified. To explore the problem we followed the fate of intravascular horseradish peroxidase (HRP) after compression injury to the thoracic cord (cats). At 90 seconds and 15 minutes, HRP was confined to the gray matter, occupying perivascular spaces, unexpanded extracellular channels, and cytoplasmic compartments of injured cells. Adjoining segments contained similar but lesser deposits. At 4 hours, tracer occupied the expanded extracellular spaces of the lesion's white matter; gray matter deposits were present up to 4 cm. distal. Vessels revealed no evidence of rupture. Open interendothelial junctions were not found. Counts of HRP-labeled vesicles in the endothelium of gray matter capillaries revealed a significant intensification of vesicular activity in the lesion and in adjacent areas up to 9 cm. caudal. Morphologically, labeled vesicles exhibited a wide diversity in shape and size. Typical pinocytotic (700A) and tubular forms measured 400 to 700 A in width; vacuolar forms measuring up to 0.7 mum. across were frequently observed. Continuity between the three types was often evident. Where basement membrane and perivascular clefts were not yet inundated with HRP, sites of vesicular emptying of HRP at the tissue front were identified. Serial sections revealed that vesicles may be contiguous from luminal to abluminal surfaces, thus providing facilitated transport pathways. The data suggest that vesicular transport plays a role in the genesis of trauma-induced edema.", "contents": "Transendothelial vesicular transport of protein following compression injury to the spinal cord. Routes of vascular leakage resulting in trauma-induced edema have not been clarified. To explore the problem we followed the fate of intravascular horseradish peroxidase (HRP) after compression injury to the thoracic cord (cats). At 90 seconds and 15 minutes, HRP was confined to the gray matter, occupying perivascular spaces, unexpanded extracellular channels, and cytoplasmic compartments of injured cells. Adjoining segments contained similar but lesser deposits. At 4 hours, tracer occupied the expanded extracellular spaces of the lesion's white matter; gray matter deposits were present up to 4 cm. distal. Vessels revealed no evidence of rupture. Open interendothelial junctions were not found. Counts of HRP-labeled vesicles in the endothelium of gray matter capillaries revealed a significant intensification of vesicular activity in the lesion and in adjacent areas up to 9 cm. caudal. Morphologically, labeled vesicles exhibited a wide diversity in shape and size. Typical pinocytotic (700A) and tubular forms measured 400 to 700 A in width; vacuolar forms measuring up to 0.7 mum. across were frequently observed. Continuity between the three types was often evident. Where basement membrane and perivascular clefts were not yet inundated with HRP, sites of vesicular emptying of HRP at the tissue front were identified. Serial sections revealed that vesicles may be contiguous from luminal to abluminal surfaces, thus providing facilitated transport pathways. The data suggest that vesicular transport plays a role in the genesis of trauma-induced edema."} {"id": "PMID:1263446", "title": "Ultrastructure of mouse mononuclear phagocytes in bone marrow colonies grown in vitro.", "content": "Recently a new method was developed to culture bone marrow cells in a liquid medium on a glass surface. Two kinds of colonies develop in these cultures, namely mononuclear phagocyte and granulocyte colonies. The study of the ultrastructure of the cells in the mononuclear phagocyte colonies was the primary aim of the present study. The architecture of the mononuclear phagocyte colonies appeared to be quite different from that of the granulocyte colonies, since in the latter, the cells lie close together in dense clusters, whereas in mononuclear phagocyte colonies the cells are more loosely dispersed with the highest cell density at the center and stellate orientation of the cells at the periphery. However, both kind of colonies grow entirely separate from each other and mixed colonies are not observed. Electron microscopy showed that there are three types of cell in the mononuclear phagocyte colonies, i.e., monoblasts, promonocytes, and macrophages. The ultrastructure of the promonocytes and macrophages of the colonies is similar to that of the same types of cell isolated directly from the mouse. The monoblast, the most immature cell of mononuclear phagocyte colonies has not been characterized before. The ultrastructure of this cell is clearly distinct from that of the promonocyte in having a round contour without pseudopods, a nuclear to cytoplasmic ratio greater than one, a cytoplasm that contains many polyribosomes, a few small granules, and a small Golgi complex surrounded by a few short strips of rough endoplasmic reticulum.", "contents": "Ultrastructure of mouse mononuclear phagocytes in bone marrow colonies grown in vitro. Recently a new method was developed to culture bone marrow cells in a liquid medium on a glass surface. Two kinds of colonies develop in these cultures, namely mononuclear phagocyte and granulocyte colonies. The study of the ultrastructure of the cells in the mononuclear phagocyte colonies was the primary aim of the present study. The architecture of the mononuclear phagocyte colonies appeared to be quite different from that of the granulocyte colonies, since in the latter, the cells lie close together in dense clusters, whereas in mononuclear phagocyte colonies the cells are more loosely dispersed with the highest cell density at the center and stellate orientation of the cells at the periphery. However, both kind of colonies grow entirely separate from each other and mixed colonies are not observed. Electron microscopy showed that there are three types of cell in the mononuclear phagocyte colonies, i.e., monoblasts, promonocytes, and macrophages. The ultrastructure of the promonocytes and macrophages of the colonies is similar to that of the same types of cell isolated directly from the mouse. The monoblast, the most immature cell of mononuclear phagocyte colonies has not been characterized before. The ultrastructure of this cell is clearly distinct from that of the promonocyte in having a round contour without pseudopods, a nuclear to cytoplasmic ratio greater than one, a cytoplasm that contains many polyribosomes, a few small granules, and a small Golgi complex surrounded by a few short strips of rough endoplasmic reticulum."} {"id": "PMID:1263507", "title": "Heterogeneity in the conformation of different protein fractions from the human erythrocyte membrane.", "content": "We have isolated 5 families of proteins from human red blood cell membranes and characterized their secondary structure by ultraviolet circular dichroism measurements. The protein families were prepared by selective solubilization from ghosts under nondenaturing conditions. We find that the intact ghost has a mean alpha-helix fraction of 0.37, whereas a low-ionic-strength extract (bands 1, 2, 5, \"spectrin\") has a substantially higher helix fraction, 0.55. Further extraction of the ghosts with para-chloromercuribenzoate yields bands 2.1, 4.1, 4.2, and 6; their helix content is only 0.17. Finally, the major intrinsic protein, band 3, was solubilized by a non-ionic detergent. Its helix fraction is 0.38.", "contents": "Heterogeneity in the conformation of different protein fractions from the human erythrocyte membrane. We have isolated 5 families of proteins from human red blood cell membranes and characterized their secondary structure by ultraviolet circular dichroism measurements. The protein families were prepared by selective solubilization from ghosts under nondenaturing conditions. We find that the intact ghost has a mean alpha-helix fraction of 0.37, whereas a low-ionic-strength extract (bands 1, 2, 5, \"spectrin\") has a substantially higher helix fraction, 0.55. Further extraction of the ghosts with para-chloromercuribenzoate yields bands 2.1, 4.1, 4.2, and 6; their helix content is only 0.17. Finally, the major intrinsic protein, band 3, was solubilized by a non-ionic detergent. Its helix fraction is 0.38."} {"id": "PMID:1263508", "title": "The exchange of erythrocyte membrane phospholipids with rat liver extracts in vitro.", "content": "Intact rat or human erythrocytes and their isolated (ghost) membranes were incubated with the high speed supernatant fraction of homogenates derived from 32P-labeled rat livers. Phospholipid molecules were transferred between the red cell membranes and the liver extracts, as reflected by the convergence of their specific radioactivities with time. Whereas ghosts usually approached isotopic equilibrium with the liver supernatant fraction during a few hours of incubation at 37 degrees C, the exchange of phospholipids by intact cells was no more than one-half, even after 18 hr. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and sphingomyelin were all exchanged in both intact cells and ghosts, albeit to different extents. (A control experiment, incubating 32P-labeled rat erythrocytes or ghosts with unlabeled rat liver extracts, also demonstrated the exchange of all four major phospholipids.) These data may signify that the phospholipids on the cytoplasmic side of the membrane of intact erythrocytes do not exchange with the phospholipids in exogenous liver extracts. If so, all four major phospholipid classes would appear to be present to some extent at both membrane surfaces. The first inference is in agreement with several other studies on this membrane, while the second inference is not.", "contents": "The exchange of erythrocyte membrane phospholipids with rat liver extracts in vitro. Intact rat or human erythrocytes and their isolated (ghost) membranes were incubated with the high speed supernatant fraction of homogenates derived from 32P-labeled rat livers. Phospholipid molecules were transferred between the red cell membranes and the liver extracts, as reflected by the convergence of their specific radioactivities with time. Whereas ghosts usually approached isotopic equilibrium with the liver supernatant fraction during a few hours of incubation at 37 degrees C, the exchange of phospholipids by intact cells was no more than one-half, even after 18 hr. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and sphingomyelin were all exchanged in both intact cells and ghosts, albeit to different extents. (A control experiment, incubating 32P-labeled rat erythrocytes or ghosts with unlabeled rat liver extracts, also demonstrated the exchange of all four major phospholipids.) These data may signify that the phospholipids on the cytoplasmic side of the membrane of intact erythrocytes do not exchange with the phospholipids in exogenous liver extracts. If so, all four major phospholipid classes would appear to be present to some extent at both membrane surfaces. The first inference is in agreement with several other studies on this membrane, while the second inference is not."} {"id": "PMID:1263509", "title": "The cytochemical localization of adenylate cyclase activity in mucous and serous cells of the salivary gland.", "content": "The present study was undertaken to localize adenylate cyclase activity in salivary glands by cytochemical means. For the study, serous parotid glands and mixed sublingual glands of the rat were used. Pieces of the fixed glands were incubated with adenosine triphosphate (ATP) or adenylyl-imidodiphosphate (AMP-PNP) as substrate: inorganic pyrophosphate or PNP liberated upon the action of adenylate cyclase on the substrates is precipitated by lead ions at their sites of production. In both glands, the reaction product was detected along the myoepithelial cell membranes in contact with secretory cells, indicating that a high level of adenylate cyclase activity occurs in association with these cell membranes. The association with a high level of the enzyme activity might be related to the contractile nature of myoepithelial cells which are supposed to aid secretory cells in discharging secretion products. A high level of adenylate cyclase activity was also detected associated with serous secretory cells (acinar cells of the parotid gland and demilune cells of the sublingual gland), but not with mucous secretory cells. In serous cells, deposits of reaction product were localized along the extracellular space of the apical cell membrane bordering the lumen. This is the portion of the cell membrane which fuses with the granule membranes during secretion. Since the granule membranes are not associated with a detectable level of adenylate cyclase activity, it appears that the enzyme activity becomes activated or associated with the granule membranes as they become part of the cell membrane by fusion. The association with a high level of adenylate cyclase activity appears to be related to the ability of the membrane to fuse with other membranes. It is likely, since the luminal membrane of mucous cells which does not fuse with mucous granule membranes during secretion is not associated with a detectable enzyme activity.", "contents": "The cytochemical localization of adenylate cyclase activity in mucous and serous cells of the salivary gland. The present study was undertaken to localize adenylate cyclase activity in salivary glands by cytochemical means. For the study, serous parotid glands and mixed sublingual glands of the rat were used. Pieces of the fixed glands were incubated with adenosine triphosphate (ATP) or adenylyl-imidodiphosphate (AMP-PNP) as substrate: inorganic pyrophosphate or PNP liberated upon the action of adenylate cyclase on the substrates is precipitated by lead ions at their sites of production. In both glands, the reaction product was detected along the myoepithelial cell membranes in contact with secretory cells, indicating that a high level of adenylate cyclase activity occurs in association with these cell membranes. The association with a high level of the enzyme activity might be related to the contractile nature of myoepithelial cells which are supposed to aid secretory cells in discharging secretion products. A high level of adenylate cyclase activity was also detected associated with serous secretory cells (acinar cells of the parotid gland and demilune cells of the sublingual gland), but not with mucous secretory cells. In serous cells, deposits of reaction product were localized along the extracellular space of the apical cell membrane bordering the lumen. This is the portion of the cell membrane which fuses with the granule membranes during secretion. Since the granule membranes are not associated with a detectable level of adenylate cyclase activity, it appears that the enzyme activity becomes activated or associated with the granule membranes as they become part of the cell membrane by fusion. The association with a high level of adenylate cyclase activity appears to be related to the ability of the membrane to fuse with other membranes. It is likely, since the luminal membrane of mucous cells which does not fuse with mucous granule membranes during secretion is not associated with a detectable enzyme activity."} {"id": "PMID:1263510", "title": "Some kinetic and chromatographic properties of detergent-dispersed adenylate cyclase.", "content": "Studies on the reaction kinetics and chromatographic properties of detergent-dispersed adenylate cyclase are described. Detergent-dispersed enzyme was prepared from whole rat cerebellum and from partially purified plasma membranes from rat liver. Data were simulated to fit kinetic models for which an inhibitor is added in constant proportion to the variable substrate. Models were chosen to distinguish whether the adenylate cyclase reaction may be controlled by an inhibitory action of free ATP--4 (or HATP--3) or by a stimulatory action of free divalent cations. The various kinetic models were then tested with the dispersed brain adenylate cyclase with both Mg++ and Mn++ and in two different buffer systems. The experimental data indicate that this enzyme has a distinct cation binding site, but exhibits no significant inhibition by HATP--3 or ATP--4. The detergent-dispersed adenylate cyclase both from liver plasma membranes and from brain have been chromatographed on anion exchange material and have been subjected to gel filtration. The presence of detergent was required for elution of cyclase activity from DEAE-Sephadex but was not required when DEAE-agarose was used. Dispersed brain cyclase was also chromatographed on agarose-NH(CH2)3NH(CH2)3-NH2 which exhibits both ionic and hydrophobic properties. Fifty percent of the applied activity was recovered with a fivefold increase in specific activity. The data suggest that the relative effectiveness of a given chromatographic procedure for detergent-dispersed adenylate cyclase may reflect the influence of both hydrophobic and ionic factors.", "contents": "Some kinetic and chromatographic properties of detergent-dispersed adenylate cyclase. Studies on the reaction kinetics and chromatographic properties of detergent-dispersed adenylate cyclase are described. Detergent-dispersed enzyme was prepared from whole rat cerebellum and from partially purified plasma membranes from rat liver. Data were simulated to fit kinetic models for which an inhibitor is added in constant proportion to the variable substrate. Models were chosen to distinguish whether the adenylate cyclase reaction may be controlled by an inhibitory action of free ATP--4 (or HATP--3) or by a stimulatory action of free divalent cations. The various kinetic models were then tested with the dispersed brain adenylate cyclase with both Mg++ and Mn++ and in two different buffer systems. The experimental data indicate that this enzyme has a distinct cation binding site, but exhibits no significant inhibition by HATP--3 or ATP--4. The detergent-dispersed adenylate cyclase both from liver plasma membranes and from brain have been chromatographed on anion exchange material and have been subjected to gel filtration. The presence of detergent was required for elution of cyclase activity from DEAE-Sephadex but was not required when DEAE-agarose was used. Dispersed brain cyclase was also chromatographed on agarose-NH(CH2)3NH(CH2)3-NH2 which exhibits both ionic and hydrophobic properties. Fifty percent of the applied activity was recovered with a fivefold increase in specific activity. The data suggest that the relative effectiveness of a given chromatographic procedure for detergent-dispersed adenylate cyclase may reflect the influence of both hydrophobic and ionic factors."} {"id": "PMID:1263511", "title": "The HLB dependency for detergent solubilization of hormonally sensitive adenylate cyclase.", "content": "The HLB dependency for the solubilization of membrane proteins and adenylate cyclase activity from a plasma membrane-enriched fraction from rat liver has been determined. The HLB (hydrophilic/lipophilic/balance) number of a detergent is an empirical measure of its relative hydrophobicity. Detergent HLB numbers vary systematically with the length of the ethylene oxide chain for a homologous series of detergents such as the Triton X series. These detergents have a constant hydrophobic moiety, octylphenyl, and a variable polar portion, polyethoxyethanol. Basal-NaF-epinephrine-, and glucagon-stimulated adenylate cyclase activities were solubilized in the HLB range of 16.8-17.4. Solubilization was most effective in 0.01 M Tris buffers at pH 7.5 containing 1-5 mM mercaptoethanol, 1 mM MgCl2, and 0.1% Triton X-305. The detergent to membrane protein ratio used in these studies was 3:1. Criteria for solubilization included lack of sedimentation at 100,000 X g, the absence of particulate material in the supernatant when examined by electron microscopy, and inclusion of hormonally sensitive adenylate cyclase activity in Sephadex G-200 gels. The apparent molecular weight of the solubilized enzyme was approximately 200,000 in the presence of Triton X-305. The solubilized enzyme was stimulated 5-fold by NaF, 7-fold by glucagon, and 20-fold by epinephrine compared to the particulate enzyme used in this study which was stimulated 10-fold, 3.4-fold, and 4-fold by NaF, epinephrine, and glucagon, respectively. The solubilized enzyme is stable for several weeks when stored at -60 degrees C.", "contents": "The HLB dependency for detergent solubilization of hormonally sensitive adenylate cyclase. The HLB dependency for the solubilization of membrane proteins and adenylate cyclase activity from a plasma membrane-enriched fraction from rat liver has been determined. The HLB (hydrophilic/lipophilic/balance) number of a detergent is an empirical measure of its relative hydrophobicity. Detergent HLB numbers vary systematically with the length of the ethylene oxide chain for a homologous series of detergents such as the Triton X series. These detergents have a constant hydrophobic moiety, octylphenyl, and a variable polar portion, polyethoxyethanol. Basal-NaF-epinephrine-, and glucagon-stimulated adenylate cyclase activities were solubilized in the HLB range of 16.8-17.4. Solubilization was most effective in 0.01 M Tris buffers at pH 7.5 containing 1-5 mM mercaptoethanol, 1 mM MgCl2, and 0.1% Triton X-305. The detergent to membrane protein ratio used in these studies was 3:1. Criteria for solubilization included lack of sedimentation at 100,000 X g, the absence of particulate material in the supernatant when examined by electron microscopy, and inclusion of hormonally sensitive adenylate cyclase activity in Sephadex G-200 gels. The apparent molecular weight of the solubilized enzyme was approximately 200,000 in the presence of Triton X-305. The solubilized enzyme was stimulated 5-fold by NaF, 7-fold by glucagon, and 20-fold by epinephrine compared to the particulate enzyme used in this study which was stimulated 10-fold, 3.4-fold, and 4-fold by NaF, epinephrine, and glucagon, respectively. The solubilized enzyme is stable for several weeks when stored at -60 degrees C."} {"id": "PMID:1263512", "title": "Perturbation of the chemotactic tumbling of bacteria.", "content": "The bacterial sensing system has been studied on three levels. First, a quantitative method has been devised for measuring the \"action spectrum\" of the bacterium in response to a sudden addition of attractant. Second, a technique has been developed for the rapid isolation of mutants defective in the transmission part of the sensing system. Third, a study of the effects of light on the transmission system reveals two components, one which generates, tumbling and another which inhibits it.", "contents": "Perturbation of the chemotactic tumbling of bacteria. The bacterial sensing system has been studied on three levels. First, a quantitative method has been devised for measuring the \"action spectrum\" of the bacterium in response to a sudden addition of attractant. Second, a technique has been developed for the rapid isolation of mutants defective in the transmission part of the sensing system. Third, a study of the effects of light on the transmission system reveals two components, one which generates, tumbling and another which inhibits it."} {"id": "PMID:1263513", "title": "Binding of agonists and antagonists to muscarinic receptors.", "content": "The binding of one irreversible and two reversible radioactive antagonists to muscarinic receptors in synaptosome preparations of rat cerebral cortex has been studied. The ligands all bind to the same receptor pool and directly and competitively yield self-consistent binding constants closely similar to those obtained by pharmacological methods on intact smooth muscle. The binding process for antagonists seems to be a simple mass action-determined process with a Hill slope of 1.0. The quantitative correlations strongly support the view that the receptor studied by ligand binding corresponds to the receptor studied by pharmacological methods. Inhibition of antagonist binding by most agonists shows a reduced Hill slope which also applies to direct binding studies of [3H] acetylcholine. Mechansims that might account for the behavior of agonists are discussed but do not conclusively point to any single mechanism.", "contents": "Binding of agonists and antagonists to muscarinic receptors. The binding of one irreversible and two reversible radioactive antagonists to muscarinic receptors in synaptosome preparations of rat cerebral cortex has been studied. The ligands all bind to the same receptor pool and directly and competitively yield self-consistent binding constants closely similar to those obtained by pharmacological methods on intact smooth muscle. The binding process for antagonists seems to be a simple mass action-determined process with a Hill slope of 1.0. The quantitative correlations strongly support the view that the receptor studied by ligand binding corresponds to the receptor studied by pharmacological methods. Inhibition of antagonist binding by most agonists shows a reduced Hill slope which also applies to direct binding studies of [3H] acetylcholine. Mechansims that might account for the behavior of agonists are discussed but do not conclusively point to any single mechanism."} {"id": "PMID:1263514", "title": "Effect ofcholinergic ligands on the lipids of acetylcholine receptor-rich membrane preparations from Torpedo californica.", "content": "Ion permeation, triggered by ligand-receptor interaction, is associated with the primary events of membrane depolarization at the neuromuscular junction and synaptic connections. To explore the possible sites of ion permeation, the long-lived fluorescent probe pyrene (fluorescence lifetime approximately 400 nsec) has been inserted into the lipid phase of acetylcholine receptor-rich membrane (AcChR-M) preparations from Torpedo californica. The pyrene probe is susceptible to both fluidity and permeability changes in the lipid bilayer. These changes are detected by variations in the rate of decay of the excited singlet state of pyrene after pulsation with a 10-nsec ruby laser flash. Variations of these lifetimes in the membrane preparations alone or in the presence of quenchers show that binding of cholinergic agonists and antagonists, neurotoxins, and local anesthetics to AcChR-M produces varying effects on the properties of the pyrene probe in the lipid phase. It is concluded that binding of cholinergic ligands to the receptor does not significantly alter the fluidity of permeability of the lipids in the bilayer contact with pyrene. On the other hand, local anesthetics do affect these properties.", "contents": "Effect ofcholinergic ligands on the lipids of acetylcholine receptor-rich membrane preparations from Torpedo californica. Ion permeation, triggered by ligand-receptor interaction, is associated with the primary events of membrane depolarization at the neuromuscular junction and synaptic connections. To explore the possible sites of ion permeation, the long-lived fluorescent probe pyrene (fluorescence lifetime approximately 400 nsec) has been inserted into the lipid phase of acetylcholine receptor-rich membrane (AcChR-M) preparations from Torpedo californica. The pyrene probe is susceptible to both fluidity and permeability changes in the lipid bilayer. These changes are detected by variations in the rate of decay of the excited singlet state of pyrene after pulsation with a 10-nsec ruby laser flash. Variations of these lifetimes in the membrane preparations alone or in the presence of quenchers show that binding of cholinergic agonists and antagonists, neurotoxins, and local anesthetics to AcChR-M produces varying effects on the properties of the pyrene probe in the lipid phase. It is concluded that binding of cholinergic ligands to the receptor does not significantly alter the fluidity of permeability of the lipids in the bilayer contact with pyrene. On the other hand, local anesthetics do affect these properties."} {"id": "PMID:1263515", "title": "The regulatory control of beta-receptor dependent adenylate cyclase.", "content": "The characteristics of the beta-receptor in turkey erythrocyte adenylate cyclase were studied using both kinetics of enzyme activation and direct binding measurement of the beta-agonists and antagonists to the beta-receptor. The regulatory ligands Gpp(NH)p and Ca2+ do not have any direct effect on the beta-receptor, but modulate the enzyme activity through the interaction with specific regulatory sites.", "contents": "The regulatory control of beta-receptor dependent adenylate cyclase. The characteristics of the beta-receptor in turkey erythrocyte adenylate cyclase were studied using both kinetics of enzyme activation and direct binding measurement of the beta-agonists and antagonists to the beta-receptor. The regulatory ligands Gpp(NH)p and Ca2+ do not have any direct effect on the beta-receptor, but modulate the enzyme activity through the interaction with specific regulatory sites."} {"id": "PMID:1263516", "title": "Reconstitution of a purified acetylcholine receptor.", "content": "Dialysis of the purified acetylcholine receptor from Torpedo californica electroplax with lipids from the same organ results in a vesicular membrane system in which the receptor is embedded in the bilayer and oriented so that most of the neurotoxin-binding sites appear to be on the outer surface. The reconstituted vesicles are chemically excitable by acetylcholine and carbamylcholine, as measured by 22Na+ efflux. The excitability is specifically blocked by the antagonist alpha-bungarotoxin. These results demonstrate that the purified reconstituted receptor system not only can specifically bind neurotransmitter but can also trigger ion translocation. It therefore has the properties necessary to effect postsynaptic depolarization in vivo.", "contents": "Reconstitution of a purified acetylcholine receptor. Dialysis of the purified acetylcholine receptor from Torpedo californica electroplax with lipids from the same organ results in a vesicular membrane system in which the receptor is embedded in the bilayer and oriented so that most of the neurotoxin-binding sites appear to be on the outer surface. The reconstituted vesicles are chemically excitable by acetylcholine and carbamylcholine, as measured by 22Na+ efflux. The excitability is specifically blocked by the antagonist alpha-bungarotoxin. These results demonstrate that the purified reconstituted receptor system not only can specifically bind neurotransmitter but can also trigger ion translocation. It therefore has the properties necessary to effect postsynaptic depolarization in vivo."} {"id": "PMID:1263517", "title": "Case report of metastatic carcinoid tumor to the neck.", "content": "Since their origianl description in 1838 carcinoid tumors have interested physicians. This case represents another unusual presents another unusual presentation of a carcinoid tumor in which the cervical area has rarely been reported. In addition, it demonstrates the elusiveness of the tumor despite exhaustive diagnostic studies.", "contents": "Case report of metastatic carcinoid tumor to the neck. Since their origianl description in 1838 carcinoid tumors have interested physicians. This case represents another unusual presents another unusual presentation of a carcinoid tumor in which the cervical area has rarely been reported. In addition, it demonstrates the elusiveness of the tumor despite exhaustive diagnostic studies."} {"id": "PMID:1263518", "title": "Thoracic duct cannulation in a patient with lung cancer.", "content": "Previously the authors demonstrated limited effectiveness of tumor specific active immunotherapy adjunct to radical surgery in patients with lung cancer. In order to improve the therapeutic effectiveness, a patient with inoperable lung carcinoma was treated with a radical surgery, tumor vaccination, and \"unblocking procedures\" which consisted of splenectomy and throacic duct canulation. In vitro studies demonstrated the evidence of sensitization of the patient against his own tumor, removal of blocking factor by the thoracic duct fistual from the circulation.", "contents": "Thoracic duct cannulation in a patient with lung cancer. Previously the authors demonstrated limited effectiveness of tumor specific active immunotherapy adjunct to radical surgery in patients with lung cancer. In order to improve the therapeutic effectiveness, a patient with inoperable lung carcinoma was treated with a radical surgery, tumor vaccination, and \"unblocking procedures\" which consisted of splenectomy and throacic duct canulation. In vitro studies demonstrated the evidence of sensitization of the patient against his own tumor, removal of blocking factor by the thoracic duct fistual from the circulation."} {"id": "PMID:1263519", "title": "Analysis of variance and covariance for colorectal adenocarcinomas in man as a logical prelude to \"staging\".", "content": "This study reports initial experience at the Ellis Fischel State Cancer Hospital (EFSCH), Columbia, Missouri, with the analysis of variance and covariance as applied to the ability to predict the lethality associated with colorectal neoplasms as influenced by tumor,host, and treatment variables considered individually and as multivariate clusters. The application of the methods to the clinical setting is based on the fact that each patient has one survival time. However, in the mathematical sense, each patient is composed of many different variables interacting simultaneously in highly complex ways to determine this uniqueness. The feasibility of determining the prognostic score or weight of many variables is illustrated. The combinatory effect of these scores can provide prognostic scores for clusters of variables providing a tool of much greater specificity than is provided by traditional staging systems such as the TNM.", "contents": "Analysis of variance and covariance for colorectal adenocarcinomas in man as a logical prelude to \"staging\". This study reports initial experience at the Ellis Fischel State Cancer Hospital (EFSCH), Columbia, Missouri, with the analysis of variance and covariance as applied to the ability to predict the lethality associated with colorectal neoplasms as influenced by tumor,host, and treatment variables considered individually and as multivariate clusters. The application of the methods to the clinical setting is based on the fact that each patient has one survival time. However, in the mathematical sense, each patient is composed of many different variables interacting simultaneously in highly complex ways to determine this uniqueness. The feasibility of determining the prognostic score or weight of many variables is illustrated. The combinatory effect of these scores can provide prognostic scores for clusters of variables providing a tool of much greater specificity than is provided by traditional staging systems such as the TNM."} {"id": "PMID:1263520", "title": "Tritiated thymidine labeling index of benign and malignant human breast epithelium.", "content": "38 specimens of benign breast tissue from young women and 92 primary breast carcinomas were evaluated for tritiated thymidine ([3H]TdR) labeling index (TLI) by in vitro pulse labeling. The TLI on nonneoplastic, terminal breast ducts was significantly higher during the latter half than during the first half of the menstrual cycle (P less than 0.001), and a geometric mean TLI of 1.5 during the latter half of the cycle is consistent with approximately 47% turnover of these cells during the menstrual cycle. Ducts of fibroadenomas showed similar menstrual variation TLI. The range of TLI observed in the carcinomas was 0.04-18.6, arithmetic mean 3.7, geometric mean 2.1. The TLI of carcinomas was not significantly correlated with size of the tumor, but tended to be higher in women less than 50 yr old than in women older than 50 yr (P less than 0.05), and in the presence of two or more metastatic axillary lymph nodes than when fewer than two nodes were involved (P less than 0.02).", "contents": "Tritiated thymidine labeling index of benign and malignant human breast epithelium. 38 specimens of benign breast tissue from young women and 92 primary breast carcinomas were evaluated for tritiated thymidine ([3H]TdR) labeling index (TLI) by in vitro pulse labeling. The TLI on nonneoplastic, terminal breast ducts was significantly higher during the latter half than during the first half of the menstrual cycle (P less than 0.001), and a geometric mean TLI of 1.5 during the latter half of the cycle is consistent with approximately 47% turnover of these cells during the menstrual cycle. Ducts of fibroadenomas showed similar menstrual variation TLI. The range of TLI observed in the carcinomas was 0.04-18.6, arithmetic mean 3.7, geometric mean 2.1. The TLI of carcinomas was not significantly correlated with size of the tumor, but tended to be higher in women less than 50 yr old than in women older than 50 yr (P less than 0.05), and in the presence of two or more metastatic axillary lymph nodes than when fewer than two nodes were involved (P less than 0.02)."} {"id": "PMID:1263521", "title": "Metastatic hypernephroma to the head and neck.", "content": "Hypernephroma is one of the most common visceral adenocarcinomas which metastasize to the head and neck. The metastasis may precede discovery of the primary or follow it. The most common sites of metastatic hypernephroma to the head and neck are the sinonasal tract, skin, cervical lymphatics, and mandible. Three cases of metastatic hypernephroma are presented and one of these is the first documented report of a metastasis to the parotid gland. The other two were found in the sinonasal tract.", "contents": "Metastatic hypernephroma to the head and neck. Hypernephroma is one of the most common visceral adenocarcinomas which metastasize to the head and neck. The metastasis may precede discovery of the primary or follow it. The most common sites of metastatic hypernephroma to the head and neck are the sinonasal tract, skin, cervical lymphatics, and mandible. Three cases of metastatic hypernephroma are presented and one of these is the first documented report of a metastasis to the parotid gland. The other two were found in the sinonasal tract."} {"id": "PMID:1263531", "title": "Surgical management of congenital cardiovascular anomalies with the use of profound hypothermia and circulatory arrest. Analysis of 180 consecutive cases.", "content": "An initial series of 180 patients subjected to definitive repair of cardiac malformations during infancy is presented. The operations were performed with profound hypothermia and circulatory stasis. Statistics relating to the entire series of patients are presented and discussed, after which the results among eleven individual groups of patients categorized by type of cardiovascular lesion are analyzed. There was 113 survivors, representing an over-all mortality rate of 37 per cent. The mortality rate was highest among patients severely ill preoperatively and among those with complex malformations. Deaths were also more frequent among infants under 6 months of age and less than 5 kilograms in weight. Analysis shows a steady increase in percentage of patient survival over the years reported from December, 1967, to April, 1975.", "contents": "Surgical management of congenital cardiovascular anomalies with the use of profound hypothermia and circulatory arrest. Analysis of 180 consecutive cases. An initial series of 180 patients subjected to definitive repair of cardiac malformations during infancy is presented. The operations were performed with profound hypothermia and circulatory stasis. Statistics relating to the entire series of patients are presented and discussed, after which the results among eleven individual groups of patients categorized by type of cardiovascular lesion are analyzed. There was 113 survivors, representing an over-all mortality rate of 37 per cent. The mortality rate was highest among patients severely ill preoperatively and among those with complex malformations. Deaths were also more frequent among infants under 6 months of age and less than 5 kilograms in weight. Analysis shows a steady increase in percentage of patient survival over the years reported from December, 1967, to April, 1975."} {"id": "PMID:1263532", "title": "Special pacemaker catheter techniques. The transmediastinal placement of sensing electrodes.", "content": "The clinical utilization of atrial programmed pacemakers is limited by the lead systems available for sensing of atrial activity. The endocardial method of lead placement is burdened by a dislodgement rate of up to 30 per cent. Alternatively, the patient must submit to the risks of a thoracotomy. Thirty-one patients have been treated with a transmediastinally, retrocardially positioned atrial detector electrode. In 20 patients (65 per cent) the detector performed as desired with no postimplant revision. In 11 patients (35 per cent) corrective measures were required primarily to correct lead placement; seven of these were corrected under local anesthesia merely by pulling the catheter. Spontaneous lead dislocation occurred in four patients. Four patients (13 per cent) underwent remediastinoscopy due to cranial displacement of the detector electrode with a resulting decrease in atrial potential to less than 0.5 mV. For technical reasons, the lead placements were performed without the benefit of x-ray illumination, with only an ECG check of the posterior atrial wall, and this may account for the relatively high incidence of revision. Transmediastinal placement of sensing electrodes presents a practicable alternative to methods presently used.", "contents": "Special pacemaker catheter techniques. The transmediastinal placement of sensing electrodes. The clinical utilization of atrial programmed pacemakers is limited by the lead systems available for sensing of atrial activity. The endocardial method of lead placement is burdened by a dislodgement rate of up to 30 per cent. Alternatively, the patient must submit to the risks of a thoracotomy. Thirty-one patients have been treated with a transmediastinally, retrocardially positioned atrial detector electrode. In 20 patients (65 per cent) the detector performed as desired with no postimplant revision. In 11 patients (35 per cent) corrective measures were required primarily to correct lead placement; seven of these were corrected under local anesthesia merely by pulling the catheter. Spontaneous lead dislocation occurred in four patients. Four patients (13 per cent) underwent remediastinoscopy due to cranial displacement of the detector electrode with a resulting decrease in atrial potential to less than 0.5 mV. For technical reasons, the lead placements were performed without the benefit of x-ray illumination, with only an ECG check of the posterior atrial wall, and this may account for the relatively high incidence of revision. Transmediastinal placement of sensing electrodes presents a practicable alternative to methods presently used."} {"id": "PMID:1263533", "title": "Hemodynamic effects of pacing-induced heart rate augmentation. A study in patients early after mitral and aortic valve operations.", "content": "Heart rate augmentation induced by atrial and ventricular pacing was carried out in 23 patients early after intracardiac valve operations. The series comprised two groups of patients: 11 with aortic and 12 with mitral valve surgery. A different pattern of hemodynamic responses emerged during heart rate augmentation in each group. Atrial pacing produced, in the aortic group, a significant increase in cardiac output and mean aortic pressure and a reduction in left atrial pressure. The changes in the mitral group were not significant. During ventricular pacing the left atrial pressure rose in both groups. Although there was a decrease in the mean cardiac output in the aortic group and an increase in the mitral group, these changes did not reach statistical significance. A similar distinction between the aortic and mitral groups was observed when comparing the results of atrial and ventricular pacing at the same heart rate. The hemodynamic benefit appeared to be confined to the aortic group. The different pattern of response in each group of patients was probably due to clinical, hemodynamic, and therapeutic factors related to the condition and management of patients with each type of valve surgery.", "contents": "Hemodynamic effects of pacing-induced heart rate augmentation. A study in patients early after mitral and aortic valve operations. Heart rate augmentation induced by atrial and ventricular pacing was carried out in 23 patients early after intracardiac valve operations. The series comprised two groups of patients: 11 with aortic and 12 with mitral valve surgery. A different pattern of hemodynamic responses emerged during heart rate augmentation in each group. Atrial pacing produced, in the aortic group, a significant increase in cardiac output and mean aortic pressure and a reduction in left atrial pressure. The changes in the mitral group were not significant. During ventricular pacing the left atrial pressure rose in both groups. Although there was a decrease in the mean cardiac output in the aortic group and an increase in the mitral group, these changes did not reach statistical significance. A similar distinction between the aortic and mitral groups was observed when comparing the results of atrial and ventricular pacing at the same heart rate. The hemodynamic benefit appeared to be confined to the aortic group. The different pattern of response in each group of patients was probably due to clinical, hemodynamic, and therapeutic factors related to the condition and management of patients with each type of valve surgery."} {"id": "PMID:1263534", "title": "Late results of valvoplasty for mitral regurgitation due to rupture of chordae of the posterior (mural) cusp.", "content": "Nine patients with rupture of chordae tendinea of the posterior cusp of the mitral valve are presented. All have been treated by plication of the posterior cusp and atrial wall. The presenting postoperative features have been described: 89 per cent are markedly improved; two patients have normal heart sounds with no murmurs; 6 patients have only a Grade 1 pansystolic apical murmur. The advantages of this procedure compared with mitral valve replacement for the same condition have been presented.", "contents": "Late results of valvoplasty for mitral regurgitation due to rupture of chordae of the posterior (mural) cusp. Nine patients with rupture of chordae tendinea of the posterior cusp of the mitral valve are presented. All have been treated by plication of the posterior cusp and atrial wall. The presenting postoperative features have been described: 89 per cent are markedly improved; two patients have normal heart sounds with no murmurs; 6 patients have only a Grade 1 pansystolic apical murmur. The advantages of this procedure compared with mitral valve replacement for the same condition have been presented."} {"id": "PMID:1263535", "title": "Supravalvular stenotic mitral ring. A new case with surgical correction.", "content": "In this report, we present a case of supravalvular stenotic mitral ring in a child. The lesion created a picture of severe mitral stenosis and was successfully managed by resection of the ring. No other malformations of the mitral apparatus or left ventricular outlfow tract were found. On analyzing the diagnostic criteria, we concluded that there appears to be only one useful criterion--the angiographic morphology. However, when ther- is an associated ventricular septal defect or findings of Shone's complex, we should suspect supravalvular ring rather than any other form of mitral stenosis.", "contents": "Supravalvular stenotic mitral ring. A new case with surgical correction. In this report, we present a case of supravalvular stenotic mitral ring in a child. The lesion created a picture of severe mitral stenosis and was successfully managed by resection of the ring. No other malformations of the mitral apparatus or left ventricular outlfow tract were found. On analyzing the diagnostic criteria, we concluded that there appears to be only one useful criterion--the angiographic morphology. However, when ther- is an associated ventricular septal defect or findings of Shone's complex, we should suspect supravalvular ring rather than any other form of mitral stenosis."} {"id": "PMID:1263536", "title": "Surgical management of the bleeding aortopulmonary fistula.", "content": "A technique utilizing endobronchial intubation with a Carlens tube and a TDMAC-heparinless shunt is described for management of the actively bleeding aortopulmonary fistula. An illustrative case report is presented.", "contents": "Surgical management of the bleeding aortopulmonary fistula. A technique utilizing endobronchial intubation with a Carlens tube and a TDMAC-heparinless shunt is described for management of the actively bleeding aortopulmonary fistula. An illustrative case report is presented."} {"id": "PMID:1263537", "title": "A method of preventing air embolus in open-heart surgery.", "content": "Intraoperative air embolus following cardiac surgery poses a serious problem. Many maneuvers have been suggested in an attempt to minimize its occurrence. Partial aortic clamping, creating a cupola which collects this air, is combined with aortic venting. The use of this simple technique is described as an alternative and easily applicable trouble-free method.", "contents": "A method of preventing air embolus in open-heart surgery. Intraoperative air embolus following cardiac surgery poses a serious problem. Many maneuvers have been suggested in an attempt to minimize its occurrence. Partial aortic clamping, creating a cupola which collects this air, is combined with aortic venting. The use of this simple technique is described as an alternative and easily applicable trouble-free method."} {"id": "PMID:1263538", "title": "The significance of electrode surface area and stimulating thresholds in permanent cardiac pacing.", "content": "This paper reports a long-term clinical study of evolving chronic thresholds of cardiac stimulation in patients with implanted pacemakers and two types of permanent prevenous unipolar pacing leads. A comprehensive collection of threshold measurements is presented and analyzed. These data were accumulated over a period of more than 4 years by measuring stimulation thresholds at each of five stimulus pulse durations ranging from 0.5 to 2.5 msec. Measurements were made at initial implantation and at first (21 month) and second (42 month) reimplantations.", "contents": "The significance of electrode surface area and stimulating thresholds in permanent cardiac pacing. This paper reports a long-term clinical study of evolving chronic thresholds of cardiac stimulation in patients with implanted pacemakers and two types of permanent prevenous unipolar pacing leads. A comprehensive collection of threshold measurements is presented and analyzed. These data were accumulated over a period of more than 4 years by measuring stimulation thresholds at each of five stimulus pulse durations ranging from 0.5 to 2.5 msec. Measurements were made at initial implantation and at first (21 month) and second (42 month) reimplantations."} {"id": "PMID:1263539", "title": "Abnormalities of regional lung function associated with ventricular septal defect and pulmonary artery band.", "content": "Xenon-133 ventilation-perfusion scans and technetium-99m angiocardiograms were performed 47 times in 34 patients. All patients had ventricular septal defect (VSD), 17 with pulmonary artery band (PAB), 6 with isolated VSD, 4 with pulmonary valvar stenosis (PS), and 7 with transposition of the great arteries (d-TGA), VSD, and PAB. Patients with VSD had slightly depressed ventilation fraction of the left lung and slightly elevated perfusion fraction of the left lung, both before and after closure of the VSD. Patients with VSD and PAB had slightly depressed ventilation fraction of the left lung but perfusion fraction of the left lung that was either markedly elevated or markedly depressed. After closure of VSD and removal of PAB the perfusion abnormality returned toward normal in some patients but remained abnormal in most. The findings were similar in most patients with d-TGA. Ventilation-perfusion ratio was nearly normal in patients with VSD alone, both before and after closure of VSD. In patients with VSD with PAB the severe abnormality of ventilation-perfusion ratio returned toward normal after corrective operation but did not reach normal. There was no abnormality of distribution of perfusion along the cephalocaudal axis of the lung with the patient supine.", "contents": "Abnormalities of regional lung function associated with ventricular septal defect and pulmonary artery band. Xenon-133 ventilation-perfusion scans and technetium-99m angiocardiograms were performed 47 times in 34 patients. All patients had ventricular septal defect (VSD), 17 with pulmonary artery band (PAB), 6 with isolated VSD, 4 with pulmonary valvar stenosis (PS), and 7 with transposition of the great arteries (d-TGA), VSD, and PAB. Patients with VSD had slightly depressed ventilation fraction of the left lung and slightly elevated perfusion fraction of the left lung, both before and after closure of the VSD. Patients with VSD and PAB had slightly depressed ventilation fraction of the left lung but perfusion fraction of the left lung that was either markedly elevated or markedly depressed. After closure of VSD and removal of PAB the perfusion abnormality returned toward normal in some patients but remained abnormal in most. The findings were similar in most patients with d-TGA. Ventilation-perfusion ratio was nearly normal in patients with VSD alone, both before and after closure of VSD. In patients with VSD with PAB the severe abnormality of ventilation-perfusion ratio returned toward normal after corrective operation but did not reach normal. There was no abnormality of distribution of perfusion along the cephalocaudal axis of the lung with the patient supine."} {"id": "PMID:1263540", "title": "Surgical therapy of lung cancer.", "content": "A total of 1,615 patients with a confirmed diagnosis of lung cancer were treated at Roswell Park Memorial Institute between 1963 and 1974. Particular emphasis was given in this review to the 295 patients that underwent surgical resection of their primary lung lesion. Factors such as histology, type of resection, sex, age, staging, and degree of dissemination were considered possible influences on survival. The risks and benefits of intentional reductive or palliative surgery are considered along with the risk related to thoracotomies performed for diagnostic purposes.", "contents": "Surgical therapy of lung cancer. A total of 1,615 patients with a confirmed diagnosis of lung cancer were treated at Roswell Park Memorial Institute between 1963 and 1974. Particular emphasis was given in this review to the 295 patients that underwent surgical resection of their primary lung lesion. Factors such as histology, type of resection, sex, age, staging, and degree of dissemination were considered possible influences on survival. The risks and benefits of intentional reductive or palliative surgery are considered along with the risk related to thoracotomies performed for diagnostic purposes."} {"id": "PMID:1263541", "title": "Carcinoma of the gastric cardia and hiatal hernia.", "content": "Carcinoma of the cardia of the stomach in patients with sliding hiatal hernia is a disease of poor prognosis, since symptoms nearly always occur late in its course at an already incurable stage. Eleven cases are reviewed from the records of The New York Hospital-Cornell Medical Center from 1932 to 1975. Resectability of tumor appeared related to shorter interval between onset of symptoms and diagnosis. Barium studies combined with esophagoscopy led to correct preoperative diagnosis of malignancy in all cases.", "contents": "Carcinoma of the gastric cardia and hiatal hernia. Carcinoma of the cardia of the stomach in patients with sliding hiatal hernia is a disease of poor prognosis, since symptoms nearly always occur late in its course at an already incurable stage. Eleven cases are reviewed from the records of The New York Hospital-Cornell Medical Center from 1932 to 1975. Resectability of tumor appeared related to shorter interval between onset of symptoms and diagnosis. Barium studies combined with esophagoscopy led to correct preoperative diagnosis of malignancy in all cases."} {"id": "PMID:1263542", "title": "Familial myxomas in four siblings.", "content": "Familial myxomas of the heart are very rare, with only two previous reports noted in the literature. This report documents four siblings with myxomas, and three of these patients had two or more myxomas. One sibling had four myxomas excised. The clinical findings, history, examination, and surgical treatment are described.", "contents": "Familial myxomas in four siblings. Familial myxomas of the heart are very rare, with only two previous reports noted in the literature. This report documents four siblings with myxomas, and three of these patients had two or more myxomas. One sibling had four myxomas excised. The clinical findings, history, examination, and surgical treatment are described."} {"id": "PMID:1263543", "title": "Plasma ionic calcium levels following injection of chloride, gluconate, and gluceptate salts of calcium.", "content": "The ionic equivalency of three calcium salts was tested in 15 patients undergoing cardiac surgery with extracorporeal circulation. Of the three salts tested (chloride, gluconate, gluceptate), only calcium chloride showed a reproducible and highly significant relationship between the increase in total calcium and the increase in ionic calcium. It is suggested that extracorporeal circulation may be one clinical situation in which use of a calcium electrode may be of major value. The marked distortion of plasma proteins and pH, the addition of large amounts of citrate, and the differences between various calcium salts indicate that it is probably not possible to predict ionic calcium with assurance and that direct measurement may be necessary for optimal therapy.", "contents": "Plasma ionic calcium levels following injection of chloride, gluconate, and gluceptate salts of calcium. The ionic equivalency of three calcium salts was tested in 15 patients undergoing cardiac surgery with extracorporeal circulation. Of the three salts tested (chloride, gluconate, gluceptate), only calcium chloride showed a reproducible and highly significant relationship between the increase in total calcium and the increase in ionic calcium. It is suggested that extracorporeal circulation may be one clinical situation in which use of a calcium electrode may be of major value. The marked distortion of plasma proteins and pH, the addition of large amounts of citrate, and the differences between various calcium salts indicate that it is probably not possible to predict ionic calcium with assurance and that direct measurement may be necessary for optimal therapy."} {"id": "PMID:1263544", "title": "Blunt traumatic rupture of the atria.", "content": "The case histories of 2 patients with atrial rupture from blunt chest trauma are presented, one of whom is the tenth survivor. Based on a review of these cases and the literature, important factors in the diagnosis and treatment of this easily repairable anatomic lesion are discussed. The importance of rapid recognition and early operation are emphasized.", "contents": "Blunt traumatic rupture of the atria. The case histories of 2 patients with atrial rupture from blunt chest trauma are presented, one of whom is the tenth survivor. Based on a review of these cases and the literature, important factors in the diagnosis and treatment of this easily repairable anatomic lesion are discussed. The importance of rapid recognition and early operation are emphasized."} {"id": "PMID:1263545", "title": "Malignant pleural mesothelioma. Report of 19 cases.", "content": "Malignant pleural mesothelioma may be composed of sarcomatous, epitheliomatous or mixed cell types. They can be differentiated from localized, benign mesothelioma. Malignant pleural mesothelioma is a rapidly fatal tumor that poses serious diagnostic and therapeutic problems. A series of 19 cases was compiled at the North Carolina Baptist Hospital, and data from these cases were compared to those of other series. The average survival time was 10 months. The most common symptoms were dyspnea, chest pain, pleural effusion, and weight loss. Three patients had a definite history of exposure to asbestos; in 6 more there was a questionable exposure. The most helpful investigative screening tool was the chest roentgenogram, in that it demonstrated an intrathoracic abnormality; however, mesothelioma could not be differentiated from inflammatory reaction or bronchogenic carcinoma with pleural effusion. Sputum cytology as well as pleural effusion cytology was only suggestive of malignancy. Bronchoscopy was not helpful. Needle biopsy yielded malignant cells in 3 of 8 patients. Exploratory thoracotomy was the most accurate means of diagnosis but was frequently followed by seeding into the incision and severe, intractable incisional pain. Therapy proved to be palliative at best. Thoracotomy did not alter the course of the disease; in fact, the production of severe incisional pain was deleterious to the patient's well-being. Cordotomy done in 3 patients brought no relief. Neither radiation therapy nor chemotherapy had a significant effect on survival time or palliation.", "contents": "Malignant pleural mesothelioma. Report of 19 cases. Malignant pleural mesothelioma may be composed of sarcomatous, epitheliomatous or mixed cell types. They can be differentiated from localized, benign mesothelioma. Malignant pleural mesothelioma is a rapidly fatal tumor that poses serious diagnostic and therapeutic problems. A series of 19 cases was compiled at the North Carolina Baptist Hospital, and data from these cases were compared to those of other series. The average survival time was 10 months. The most common symptoms were dyspnea, chest pain, pleural effusion, and weight loss. Three patients had a definite history of exposure to asbestos; in 6 more there was a questionable exposure. The most helpful investigative screening tool was the chest roentgenogram, in that it demonstrated an intrathoracic abnormality; however, mesothelioma could not be differentiated from inflammatory reaction or bronchogenic carcinoma with pleural effusion. Sputum cytology as well as pleural effusion cytology was only suggestive of malignancy. Bronchoscopy was not helpful. Needle biopsy yielded malignant cells in 3 of 8 patients. Exploratory thoracotomy was the most accurate means of diagnosis but was frequently followed by seeding into the incision and severe, intractable incisional pain. Therapy proved to be palliative at best. Thoracotomy did not alter the course of the disease; in fact, the production of severe incisional pain was deleterious to the patient's well-being. Cordotomy done in 3 patients brought no relief. Neither radiation therapy nor chemotherapy had a significant effect on survival time or palliation."} {"id": "PMID:1263546", "title": "Prevention of air embolism with intravascular carbon dioxide washout.", "content": "Air embolism remains a constant hazard from all operative procedures which involve opening the central cardiovascular system. Standard surgical maneuvers have been developed to prevent embolization by evacuating the air before restoring the circulation. Under certain circumstances these maneuvers may not be effective in removing air from the aortic arch. Introduction of carbon dioxide directly into the aorta to displace blood for adequate visualization has proved to be a simple, safe adjunct to the prevention of air embolization in operations involving the aortic arch.", "contents": "Prevention of air embolism with intravascular carbon dioxide washout. Air embolism remains a constant hazard from all operative procedures which involve opening the central cardiovascular system. Standard surgical maneuvers have been developed to prevent embolization by evacuating the air before restoring the circulation. Under certain circumstances these maneuvers may not be effective in removing air from the aortic arch. Introduction of carbon dioxide directly into the aorta to displace blood for adequate visualization has proved to be a simple, safe adjunct to the prevention of air embolization in operations involving the aortic arch."} {"id": "PMID:1263547", "title": "Multiple pulmonary leiomyomatous hamartomas in women.", "content": "A rare case of multiple pulmonary leiomyomatous hamartomas is described and seven previously reported cases are reviewed. The pathological and clinical features of this lesion, which is benign and occurs in middle-aged women, are unique; a conservative approach following the establishment of diagnosis is recommended.", "contents": "Multiple pulmonary leiomyomatous hamartomas in women. A rare case of multiple pulmonary leiomyomatous hamartomas is described and seven previously reported cases are reviewed. The pathological and clinical features of this lesion, which is benign and occurs in middle-aged women, are unique; a conservative approach following the establishment of diagnosis is recommended."} {"id": "PMID:1263548", "title": "Successful prolonged heparinless venoarterial bypass in sheep.", "content": "In order to investigate the safety of prolonged heparinless venoarterial bypass (HL-VAB), we subjected 18 sheep to prolonged HL-VAB for up to 6 days. Three animals died of granulomatous lung abscess and one died from intra-abdominal abscess. One animal died of generalized thromboembolism secondary to mechanical damage of the nonthrombogenic coating occurring at the time of cannulation. HL-VAB was successfully carried out in 13 sheep. Although clots were found at all tubing connections where blood turbulence occurred, only the previously mentioned animal showed evidence of thromboembolism. Damage to the nonthrombogenic tubing exposed to the roller pump head was seen in all animals, and its severity appeared to be related to the duration of bypass. Scanning electron microscopic examination revealed scattered platelet aggregates on the nonthrombogenic coated surfaces without clinical evidence of embolization. Hematocrit values, leukocyte counts, platelet counts, prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT), plasma fibrinogen levels, and factor V and VIII levels remained unchanged, whereas free plasma hemoglobin levels rose slightly during 6 days of HL-VAB. HL-VAB for up to 6 days appears to have little adverse effect on blood cells and blood coagulation factors. For current clinical use, the nonthrombogenic coated tubing circuit should be changed every 48 hours because of time-related trauma to the coated tubing from the roller pump.", "contents": "Successful prolonged heparinless venoarterial bypass in sheep. In order to investigate the safety of prolonged heparinless venoarterial bypass (HL-VAB), we subjected 18 sheep to prolonged HL-VAB for up to 6 days. Three animals died of granulomatous lung abscess and one died from intra-abdominal abscess. One animal died of generalized thromboembolism secondary to mechanical damage of the nonthrombogenic coating occurring at the time of cannulation. HL-VAB was successfully carried out in 13 sheep. Although clots were found at all tubing connections where blood turbulence occurred, only the previously mentioned animal showed evidence of thromboembolism. Damage to the nonthrombogenic tubing exposed to the roller pump head was seen in all animals, and its severity appeared to be related to the duration of bypass. Scanning electron microscopic examination revealed scattered platelet aggregates on the nonthrombogenic coated surfaces without clinical evidence of embolization. Hematocrit values, leukocyte counts, platelet counts, prothrombin time (PT), activated partial thromboplastin time (PTT), thrombin time (TT), plasma fibrinogen levels, and factor V and VIII levels remained unchanged, whereas free plasma hemoglobin levels rose slightly during 6 days of HL-VAB. HL-VAB for up to 6 days appears to have little adverse effect on blood cells and blood coagulation factors. For current clinical use, the nonthrombogenic coated tubing circuit should be changed every 48 hours because of time-related trauma to the coated tubing from the roller pump."} {"id": "PMID:1263549", "title": "Extracorporeal oxygenation with various experimental venoarterial bypasses during prolonged apnea.", "content": "This work compares various conventional venoarterial closed-chest circuits where satisfactory oxygenation of myocardium and brain in total apnea with extracorporeal circulation is concerned. Eleven dogs were studied during 3 hours of curare-induced apnea. We used single and double vena caval drainages connected to an oxygenator. A single-vein drainage yielded approximately 50 per cent and a double-vein drainage 75 per cent bypass. Two separate roller pumps fed arterialized blood variously into carotid and femoral arteries. In single-vein drainage, the oxygen partial pressure in the coronary artery was consistently poor and carotid oxygen partial pressure was poor for 100 per cent femoral infusion while more and more arterialized blood reached the carotid arteries in the other single-vein drainage circuits. In double-vein drainage, the coronary oxygen partial pressure for 100 per cent femoral infusion remained poor while, for the other circuit types, the coronary arteries received arterialized blood except where 100 per cent carotid infusion was concerned. The carotid oxygen partial pressure was sound for all groups in the double-vein drainage except for some obtained in 100 per cent femoral infusion. Consequently, where the bypass was large and the carotid and femoral arteries received a share of arterialized blood, both heart and brain received sound oxygenation.", "contents": "Extracorporeal oxygenation with various experimental venoarterial bypasses during prolonged apnea. This work compares various conventional venoarterial closed-chest circuits where satisfactory oxygenation of myocardium and brain in total apnea with extracorporeal circulation is concerned. Eleven dogs were studied during 3 hours of curare-induced apnea. We used single and double vena caval drainages connected to an oxygenator. A single-vein drainage yielded approximately 50 per cent and a double-vein drainage 75 per cent bypass. Two separate roller pumps fed arterialized blood variously into carotid and femoral arteries. In single-vein drainage, the oxygen partial pressure in the coronary artery was consistently poor and carotid oxygen partial pressure was poor for 100 per cent femoral infusion while more and more arterialized blood reached the carotid arteries in the other single-vein drainage circuits. In double-vein drainage, the coronary oxygen partial pressure for 100 per cent femoral infusion remained poor while, for the other circuit types, the coronary arteries received arterialized blood except where 100 per cent carotid infusion was concerned. The carotid oxygen partial pressure was sound for all groups in the double-vein drainage except for some obtained in 100 per cent femoral infusion. Consequently, where the bypass was large and the carotid and femoral arteries received a share of arterialized blood, both heart and brain received sound oxygenation."} {"id": "PMID:1263550", "title": "Thrombotic phenomena with nonanticoagulated, composite-strut aortic prostheses.", "content": "Twenty-nine patients received no anticoagulant therapy after aortic valve replacement with a Starr-Edwards Model 2400 prosthesis. Hemodynamic studies were performed at 3 to 26 months (average 12 months) in 18 of 29 patients. Mean aortic valve gradients ranged from 14 to 62 mm. Hg and averaged 34 mm. Hg. Calculated aortic valve area varied from 0.20 to 1.75 sq. cm. and averaged 0.98 sq. cm. Thirteen of 18 patients had critically stenotic valve orifices. At reoperation or autopsy, examination of the prostheses consistently revealed pannus and thrombus which narrowed the inflow orifice and usually extended to the struts. Of the remaining 11 patients, 3 have died (2 suddenly and one after a cerebrovascular accident), 2 have had embolic episodes, and 6 have refused a repeat study but are being given anticoagulant therapy. Clinical examination, serum lactic dehydrogenase (LDH) levels, phonocardiography, echocardiography, and fluoroscopy of the prosthesis were often unrevealing. Cardiac catheterization was the only reliable method for critically evaluating prosthetic function. In conclusion, close follow-up, preferably with cardiac catheterization, is recommended in any patient who received a Starr-Edwards Model 2400 aortic valve prosthesis without anticoagulation. Long-term anticoagulation with sodium warfarin is indicated in all patients with a Model 2400 aortic valve prosthesis unless there is a contraindication to such therapy.", "contents": "Thrombotic phenomena with nonanticoagulated, composite-strut aortic prostheses. Twenty-nine patients received no anticoagulant therapy after aortic valve replacement with a Starr-Edwards Model 2400 prosthesis. Hemodynamic studies were performed at 3 to 26 months (average 12 months) in 18 of 29 patients. Mean aortic valve gradients ranged from 14 to 62 mm. Hg and averaged 34 mm. Hg. Calculated aortic valve area varied from 0.20 to 1.75 sq. cm. and averaged 0.98 sq. cm. Thirteen of 18 patients had critically stenotic valve orifices. At reoperation or autopsy, examination of the prostheses consistently revealed pannus and thrombus which narrowed the inflow orifice and usually extended to the struts. Of the remaining 11 patients, 3 have died (2 suddenly and one after a cerebrovascular accident), 2 have had embolic episodes, and 6 have refused a repeat study but are being given anticoagulant therapy. Clinical examination, serum lactic dehydrogenase (LDH) levels, phonocardiography, echocardiography, and fluoroscopy of the prosthesis were often unrevealing. Cardiac catheterization was the only reliable method for critically evaluating prosthetic function. In conclusion, close follow-up, preferably with cardiac catheterization, is recommended in any patient who received a Starr-Edwards Model 2400 aortic valve prosthesis without anticoagulation. Long-term anticoagulation with sodium warfarin is indicated in all patients with a Model 2400 aortic valve prosthesis unless there is a contraindication to such therapy."} {"id": "PMID:1263551", "title": "Double-outlet right ventricle with tunnel from left ventricle to aorta.", "content": "The successful surgical correction of an unusual form of double-outlet right ventricle (DORV) in a 4-year-old boy is described. A long tunnel-like structure was present between the left ventricle and the aorta and also communicated with the right ventricle. hemodynamic and angiographic evaluation demonstrated restrictive communications between the tunnel, the aorta, and each of the ventricles. A pathological concept explaining the anatomic abnormality seen in this patient is discussed.", "contents": "Double-outlet right ventricle with tunnel from left ventricle to aorta. The successful surgical correction of an unusual form of double-outlet right ventricle (DORV) in a 4-year-old boy is described. A long tunnel-like structure was present between the left ventricle and the aorta and also communicated with the right ventricle. hemodynamic and angiographic evaluation demonstrated restrictive communications between the tunnel, the aorta, and each of the ventricles. A pathological concept explaining the anatomic abnormality seen in this patient is discussed."} {"id": "PMID:1263552", "title": "Use of balloon-tipped vena caval cannulas during open cardiac surgery.", "content": "Experience over the past twelve months with the use of balloon-tipped vena caval cannulas for central cannulation during cardiopulmonary bypass is reported. Based on this experience, we fell that such cannulas should become useful to the cardiac surgeon, particularly for complex reoperation.", "contents": "Use of balloon-tipped vena caval cannulas during open cardiac surgery. Experience over the past twelve months with the use of balloon-tipped vena caval cannulas for central cannulation during cardiopulmonary bypass is reported. Based on this experience, we fell that such cannulas should become useful to the cardiac surgeon, particularly for complex reoperation."} {"id": "PMID:1263553", "title": "Long-term follow-up of cloth-covered Starr-Edwards prostheses.", "content": "One hundred patients in whom cloth-covered Starr-Edwards prostheses were implanted have now been followed for 3 to 7 years. The hospital mortality rate was 5 per cent, and survival at five years was 70 per cent. Complications related to valve design occurred in 8 per cent (4 per cent fatal). The majority of late deaths and poor results were related to progressive cardiac disease rather than valve-related complications. The results indicate that cloth-covered prostheses have significantly lowered the incidence of thromboembolism and eliminated poppet dysfunction. The problem of strut cloth wear was clinically observed only twice in 500 patient-years of follow-up.", "contents": "Long-term follow-up of cloth-covered Starr-Edwards prostheses. One hundred patients in whom cloth-covered Starr-Edwards prostheses were implanted have now been followed for 3 to 7 years. The hospital mortality rate was 5 per cent, and survival at five years was 70 per cent. Complications related to valve design occurred in 8 per cent (4 per cent fatal). The majority of late deaths and poor results were related to progressive cardiac disease rather than valve-related complications. The results indicate that cloth-covered prostheses have significantly lowered the incidence of thromboembolism and eliminated poppet dysfunction. The problem of strut cloth wear was clinically observed only twice in 500 patient-years of follow-up."} {"id": "PMID:1263554", "title": "Interference with function of unipolar pacemaker due to muscle potentials.", "content": "One hundred and seventy-three unipolar pulse generator systems were tested in 169 patients to determine the incidence of sensing of muscle potentials. One hundred and twenty-two implants in the pectoral region were suitable for assessment and 60 (49 per cent) demonstrated sensing. Ventricular-inhibited units sensed muscle potentials in 69 per cent (47 of 78), with 9 patients complaining of related symptoms. Ventricular-synchronous units sensed in 30 per cent (13 of 34) with no patient manifesting symptoms.", "contents": "Interference with function of unipolar pacemaker due to muscle potentials. One hundred and seventy-three unipolar pulse generator systems were tested in 169 patients to determine the incidence of sensing of muscle potentials. One hundred and twenty-two implants in the pectoral region were suitable for assessment and 60 (49 per cent) demonstrated sensing. Ventricular-inhibited units sensed muscle potentials in 69 per cent (47 of 78), with 9 patients complaining of related symptoms. Ventricular-synchronous units sensed in 30 per cent (13 of 34) with no patient manifesting symptoms."} {"id": "PMID:1263555", "title": "Blood and urine catecholamine concentrations after implantation of artificial heart.", "content": "Plasma and urine epinephrine and norepinephrine concentrations were measured before and after implantation of an artificial heart in 20 calves and before and after thoracotomy in 3 control calves. All animals had similar preoperative plasma and urine catecholamine concentrations. During the first 4 postoperative days, plasma and urine epinephrine and norepinephrine concentrations were markedly elevated in all animals. However, calves with an artificial heart had significantly higher concentrations than control calves. Thereafter, catecholamine levels in control animals returned to preoperative levels, whereas epinephrine concentrations in artificial heart recipients remained elevated for 2 weeks and norepinephrine concentrations remained elevated for over a month. Two artifical heart recipeints survived longer than 2 months and had normal plasma and urine catecholamine concentrations from day 32 until a few days before being put to death. Although the mechanism in unclear, these findings suggest that early artificial heart function is associated with a significant metabolic stress which slowly disappears or becomes tolerable after one month.", "contents": "Blood and urine catecholamine concentrations after implantation of artificial heart. Plasma and urine epinephrine and norepinephrine concentrations were measured before and after implantation of an artificial heart in 20 calves and before and after thoracotomy in 3 control calves. All animals had similar preoperative plasma and urine catecholamine concentrations. During the first 4 postoperative days, plasma and urine epinephrine and norepinephrine concentrations were markedly elevated in all animals. However, calves with an artificial heart had significantly higher concentrations than control calves. Thereafter, catecholamine levels in control animals returned to preoperative levels, whereas epinephrine concentrations in artificial heart recipients remained elevated for 2 weeks and norepinephrine concentrations remained elevated for over a month. Two artifical heart recipeints survived longer than 2 months and had normal plasma and urine catecholamine concentrations from day 32 until a few days before being put to death. Although the mechanism in unclear, these findings suggest that early artificial heart function is associated with a significant metabolic stress which slowly disappears or becomes tolerable after one month."} {"id": "PMID:1263556", "title": "Pulmonary valve replacement. Report of an operation performed for calcific pulmonic stenosis associated with total anomalous pulmonary venous drainage and atrial septal defect.", "content": "Calcification of the pulmonic valve is an uncommon lesion that is usually associated with other congenital cardiac defects. Prior attempts at valvotomy or partial excision of the puolmonic valve have carried a high mortality rate. Pulmonary valve replacement itself is an equally uncommon surgical procedure and, in the past, has been performed only during reconstruction of the right ventricular outflow tract, when the pulmonic valve itself had to be utilized as an aortic prosthesis, and in one patient in whom pulmonary regurgitation following valvotomy was not well tolerated. A case of calcific pulmonic stenosis in association with an atrial septal defect and total anomalous pulmonary venous drainage is reported. The patient was treated successfully by pulmonary valve replacement with a Hancock stented porcine xenograft aortic prosthesis in association with correction of the other congenital cardiac lesions.", "contents": "Pulmonary valve replacement. Report of an operation performed for calcific pulmonic stenosis associated with total anomalous pulmonary venous drainage and atrial septal defect. Calcification of the pulmonic valve is an uncommon lesion that is usually associated with other congenital cardiac defects. Prior attempts at valvotomy or partial excision of the puolmonic valve have carried a high mortality rate. Pulmonary valve replacement itself is an equally uncommon surgical procedure and, in the past, has been performed only during reconstruction of the right ventricular outflow tract, when the pulmonic valve itself had to be utilized as an aortic prosthesis, and in one patient in whom pulmonary regurgitation following valvotomy was not well tolerated. A case of calcific pulmonic stenosis in association with an atrial septal defect and total anomalous pulmonary venous drainage is reported. The patient was treated successfully by pulmonary valve replacement with a Hancock stented porcine xenograft aortic prosthesis in association with correction of the other congenital cardiac lesions."} {"id": "PMID:1263557", "title": "Effects of coronary perfusion during myocardial hypoxia. Comparison of metabolic and hemodynamic events with global ischemia and hypoxemia.", "content": "The effects of metabolic accumulation on myocardial metabolism during global heart oxygen deprivation were evaluated in a working in situ swine heart preparation with controlled total coronary blood flow. Myocardial oxygen consumption was depressed to a similar extent by either reducing total coronary flow 60 per cent (ischemia, low coronary perfusion) in 10 swine or by decreasing coronary perfusate PO2 to 30 mm. Hg at normal flows (hypoxemia, high coronary perfusion) in 13 swine. Compared with findings in 13 control hearts, ischemia significantly (p less than 0.05) decreased myocardial oxygen consumption (640 to 390 mumole per hour per gram), glucose uptake (185 to 16 mumole per hour per gram), and free fatty acid consumption (32 to 17 mumole per hour per gram). ttissue levels of glycogen, creatine phosphate, and adenosine triphosphate (tatp) were significantly reduced (p less than 0.005), and tissue lactate, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were increased (p less than 0.001). During hypoxemia, glucose uptake was increased (240 mumole per hour per gram) and free fatty acid consumption was somewhat less depressed (19 mumole per hour per gram). Creatine phosphate and ATP were higher than with ischemia (p less than 0.01), and lactate, ADP, and AMP accumulations were less (p less than 0.01). Thus, in the period immediately following myocardial oxygen deprivation, inadequate coronary perfusion caused greater metabolic buildup which inhibited myocardial substrate utilization and energy production. High coronary perfusion, even though the perfusate was unoxygenated, was associated with greater preservation of substrate utilization, higher levels of high-energy phosphates, less accumulation of metabolic products, and a longer survival. These data suggest a critical role of coronary perfusion in protecting myocardial metabolism in the immediate period following global heart hypoxia.", "contents": "Effects of coronary perfusion during myocardial hypoxia. Comparison of metabolic and hemodynamic events with global ischemia and hypoxemia. The effects of metabolic accumulation on myocardial metabolism during global heart oxygen deprivation were evaluated in a working in situ swine heart preparation with controlled total coronary blood flow. Myocardial oxygen consumption was depressed to a similar extent by either reducing total coronary flow 60 per cent (ischemia, low coronary perfusion) in 10 swine or by decreasing coronary perfusate PO2 to 30 mm. Hg at normal flows (hypoxemia, high coronary perfusion) in 13 swine. Compared with findings in 13 control hearts, ischemia significantly (p less than 0.05) decreased myocardial oxygen consumption (640 to 390 mumole per hour per gram), glucose uptake (185 to 16 mumole per hour per gram), and free fatty acid consumption (32 to 17 mumole per hour per gram). ttissue levels of glycogen, creatine phosphate, and adenosine triphosphate (tatp) were significantly reduced (p less than 0.005), and tissue lactate, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were increased (p less than 0.001). During hypoxemia, glucose uptake was increased (240 mumole per hour per gram) and free fatty acid consumption was somewhat less depressed (19 mumole per hour per gram). Creatine phosphate and ATP were higher than with ischemia (p less than 0.01), and lactate, ADP, and AMP accumulations were less (p less than 0.01). Thus, in the period immediately following myocardial oxygen deprivation, inadequate coronary perfusion caused greater metabolic buildup which inhibited myocardial substrate utilization and energy production. High coronary perfusion, even though the perfusate was unoxygenated, was associated with greater preservation of substrate utilization, higher levels of high-energy phosphates, less accumulation of metabolic products, and a longer survival. These data suggest a critical role of coronary perfusion in protecting myocardial metabolism in the immediate period following global heart hypoxia."} {"id": "PMID:1263558", "title": "Fatal cerebral atheromatous embolization after cardiopulmonary bypass.", "content": "Cholesterol embolization to the abdominal viscera is common. Fatal cholesterol embolization to the central nervous system is rare. This report describes a 55-year-old woman with severe atherosclerotic disease who underwent cardiac surgery during which she suffered a fatal cerebrovascular accident. Postmortem examination revealed multiple infarcts in the brain, eye, and spleen due to emboli of cholesterol crystals and other atheromatous debris from a ruptured atherosclerotic plaque in the ascending aorta at the site of an aortotomy for cardiopulmonary bypass. In patients known to have severe atherosclerotic disease, atheromatous embolization to the central nervous system should be regarded as a potential complication of surgical manipulation and incision of the aorta for cardiopulmonary bypass. Ophthalmoscopic examination may be of diagnostic value in such cases.", "contents": "Fatal cerebral atheromatous embolization after cardiopulmonary bypass. Cholesterol embolization to the abdominal viscera is common. Fatal cholesterol embolization to the central nervous system is rare. This report describes a 55-year-old woman with severe atherosclerotic disease who underwent cardiac surgery during which she suffered a fatal cerebrovascular accident. Postmortem examination revealed multiple infarcts in the brain, eye, and spleen due to emboli of cholesterol crystals and other atheromatous debris from a ruptured atherosclerotic plaque in the ascending aorta at the site of an aortotomy for cardiopulmonary bypass. In patients known to have severe atherosclerotic disease, atheromatous embolization to the central nervous system should be regarded as a potential complication of surgical manipulation and incision of the aorta for cardiopulmonary bypass. Ophthalmoscopic examination may be of diagnostic value in such cases."} {"id": "PMID:1263559", "title": "Operative indication for corrective surgery in cases of complete transposition of the great arteries associated with large ventricular septal defect.", "content": "Among 23 patients with complete transposition of the great arteries (TGA) and large ventricular septal defect (VSD) who underwent corrective surgery, there were nine deaths (39 per cent). Since 1972, improvement in operative techniques, linked with increasing experience in postoperative care, has reduced the hospital mortality rate to 29 per cent (five deaths in 17 patients). Only one of these 23 patients had pulmonary artery banding prior to definitive repair. Analysis of the preoperative hemodynamic data suggests that complete surgical repair is not indicated for patients who have TGA and large VSD, without significant pulmonary stensosis, when the pulmonary arteriolar resistance is greater than 2,500 dynes-sec.-cm.-5 or the effective pulmonary flow index is less than 1.2 L. per minute per square meter of body surface area.", "contents": "Operative indication for corrective surgery in cases of complete transposition of the great arteries associated with large ventricular septal defect. Among 23 patients with complete transposition of the great arteries (TGA) and large ventricular septal defect (VSD) who underwent corrective surgery, there were nine deaths (39 per cent). Since 1972, improvement in operative techniques, linked with increasing experience in postoperative care, has reduced the hospital mortality rate to 29 per cent (five deaths in 17 patients). Only one of these 23 patients had pulmonary artery banding prior to definitive repair. Analysis of the preoperative hemodynamic data suggests that complete surgical repair is not indicated for patients who have TGA and large VSD, without significant pulmonary stensosis, when the pulmonary arteriolar resistance is greater than 2,500 dynes-sec.-cm.-5 or the effective pulmonary flow index is less than 1.2 L. per minute per square meter of body surface area."} {"id": "PMID:1263560", "title": "Improved technique of double valve replacement.", "content": "Double valve replacement in the aortic and mitral positions continues to present significant morbidity and mortality rates. At present, the replacement operation is performed with the use of either ischemic arrest or coronary perfusion. In this report, we describe a new method whereby the anterior portion of the mitral valve and the aortic valve are replaced with the aid of ischemic arrest, and then the posterior portion of the mitral valve and left atrium are repaired while the myocardium is being perfused through the native ostium. This technique has been used in 33 patients with one operative death in the last 4 years and has significantly reduced our mortality rate in this time.", "contents": "Improved technique of double valve replacement. Double valve replacement in the aortic and mitral positions continues to present significant morbidity and mortality rates. At present, the replacement operation is performed with the use of either ischemic arrest or coronary perfusion. In this report, we describe a new method whereby the anterior portion of the mitral valve and the aortic valve are replaced with the aid of ischemic arrest, and then the posterior portion of the mitral valve and left atrium are repaired while the myocardium is being perfused through the native ostium. This technique has been used in 33 patients with one operative death in the last 4 years and has significantly reduced our mortality rate in this time."} {"id": "PMID:1263561", "title": "The selection of patients with bronchogenic carcinoma for mediastinoscopy.", "content": "The records of 112 patients treated at the Ochsner Foundation Hospital with the diagnosis of bronchogenic carcinoma were reviewed. A new concept for defining the location of central versus peripheral tumors is presented. Criteria important in selection of patients for whom mediastinoscopy is likely to be helpful are cell type, location (peripheral versus central), and radiographic evidence of mediastinal metastasis. The size of the tumor is not a useful criterion except possibly for squamous cell lesions. A high incidence of mediastinal metasis was found associated with central tumors (63 to 100 per cent) of all cell types and with peripheral lesions (63 per cent) of undifferentiated cell types. A relatively low incidence of mediastinal metasis was associated with peripheral asenocarcinomas or squamous cell tumors. We would, therefore, recommend mediastinoscopy for all patients with central lesions and those patients with peripheral lesions of an undifferentiated cell type. When correlated with radiographic findings, only 4.6 per cent of peripheral carcinomas of a differentiated cell type with a radiographically normal mediastinum were found to produce mediastinal metastases, and mediastinoscopy is not recommended. In patients with peripheral tumors of indeterminate cell type, a decision for mediastinoscopy may be influenced by other factors such as the operative risk of a thoracotomy and location of the primary tumor within the lung.", "contents": "The selection of patients with bronchogenic carcinoma for mediastinoscopy. The records of 112 patients treated at the Ochsner Foundation Hospital with the diagnosis of bronchogenic carcinoma were reviewed. A new concept for defining the location of central versus peripheral tumors is presented. Criteria important in selection of patients for whom mediastinoscopy is likely to be helpful are cell type, location (peripheral versus central), and radiographic evidence of mediastinal metastasis. The size of the tumor is not a useful criterion except possibly for squamous cell lesions. A high incidence of mediastinal metasis was found associated with central tumors (63 to 100 per cent) of all cell types and with peripheral lesions (63 per cent) of undifferentiated cell types. A relatively low incidence of mediastinal metasis was associated with peripheral asenocarcinomas or squamous cell tumors. We would, therefore, recommend mediastinoscopy for all patients with central lesions and those patients with peripheral lesions of an undifferentiated cell type. When correlated with radiographic findings, only 4.6 per cent of peripheral carcinomas of a differentiated cell type with a radiographically normal mediastinum were found to produce mediastinal metastases, and mediastinoscopy is not recommended. In patients with peripheral tumors of indeterminate cell type, a decision for mediastinoscopy may be influenced by other factors such as the operative risk of a thoracotomy and location of the primary tumor within the lung."} {"id": "PMID:1263562", "title": "Left aortic arch with right descending aorta and right ligamentum arteriosum. A rare form of vascular ring.", "content": "The combination of left aortic arch, right descending aorta, and right patent ductus arteriosus is a rare form of aortic arch anomaly. Only 11 such cases have been previously reported. A 6-month-old infant with this anomaly manifested severe respiratory difficulty and feeding problems in the early newborn period. The aortic arch abnormalities were confirmed by angiocardiography, and operative correction was successful. This is the first case reported in which the patient developed severe respiratory and feeding difficulties due to this type of a vascular ring.", "contents": "Left aortic arch with right descending aorta and right ligamentum arteriosum. A rare form of vascular ring. The combination of left aortic arch, right descending aorta, and right patent ductus arteriosus is a rare form of aortic arch anomaly. Only 11 such cases have been previously reported. A 6-month-old infant with this anomaly manifested severe respiratory difficulty and feeding problems in the early newborn period. The aortic arch abnormalities were confirmed by angiocardiography, and operative correction was successful. This is the first case reported in which the patient developed severe respiratory and feeding difficulties due to this type of a vascular ring."} {"id": "PMID:1263563", "title": "Nonsurgical removal of foreign body from right heart. A new percutaneous approach.", "content": "A new method is described for the nonsurgical removal of foreign bodies from the right heart. By means of the percutaneous Seldinger Technique, endoscopic forceps were passed throught the internal jugular vein to remove a fragment of polyvinyl catheter from the right atrium of a patient who had had heart surgery. The procedure is atraumatic and can be performed on patients who are critically ill and those who recently have had surgery.", "contents": "Nonsurgical removal of foreign body from right heart. A new percutaneous approach. A new method is described for the nonsurgical removal of foreign bodies from the right heart. By means of the percutaneous Seldinger Technique, endoscopic forceps were passed throught the internal jugular vein to remove a fragment of polyvinyl catheter from the right atrium of a patient who had had heart surgery. The procedure is atraumatic and can be performed on patients who are critically ill and those who recently have had surgery."} {"id": "PMID:1263564", "title": "Anomalous origin of the left coronary artery from the right pulmonary artery.", "content": "A previously unknown coronary artery anomaly is reported: origin of the left coronary artery from the right pulmonary artery. This unusual anomaly can probably be explained by the theory of dual embryonic development of the coronary arteries from angioblastic buds in the truncus arteriosus. It is thought that these buds anastomose with a capillary network that is developing on the surface of the ventricles. Complete repair of this lesion with restoration of a two-coronary artery system was accomplished in a 10-month-old baby. The coronary artery was detached from the pulmonary artery, with a button of pulmonary artery being retained around the coronary artery ostium. Direct systemic arterial flow to the left coronary artery was established by anastomosis of the left coronary to the right subclavian artery.", "contents": "Anomalous origin of the left coronary artery from the right pulmonary artery. A previously unknown coronary artery anomaly is reported: origin of the left coronary artery from the right pulmonary artery. This unusual anomaly can probably be explained by the theory of dual embryonic development of the coronary arteries from angioblastic buds in the truncus arteriosus. It is thought that these buds anastomose with a capillary network that is developing on the surface of the ventricles. Complete repair of this lesion with restoration of a two-coronary artery system was accomplished in a 10-month-old baby. The coronary artery was detached from the pulmonary artery, with a button of pulmonary artery being retained around the coronary artery ostium. Direct systemic arterial flow to the left coronary artery was established by anastomosis of the left coronary to the right subclavian artery."} {"id": "PMID:1263565", "title": "Heparinless, oxygenatorless perfusion rewarming following surface-induced deep hypothermia for open-heart surgery.", "content": "To facilitate perfusion rewarming without the use of total body heparinization or an oxygenator following open-heart correction with surface hypothermia, we divised a pump circuit. The circuit, totally primed with 100 c.c. of saline, consists of polyurethane-polyvinyl-graphite (PPG) coated Tygon tubes (with one end tapered by heat treatment) and a copper-coil heat exchanger. A roller pump was used to achieve partial bypass from the left atrium to the ascending aorta with flow rates up to 70 c.c. per kilogram per minute. Experiments in dogs resulted in rapid rewarming, immediate return of cardiac function, and hematologic alterations similar to those noted during surface rewarming. The safety of the method was also demonstrated. Prothrombin time, partial thromboplastin time, and platelet values returned to control levels upon rewarming, and no thromboemboli or bleeding problems were noted. Six clinical experiences were accumulated. Details of the method, hematologic and blood chemical analyses in dogs, and the first clinical trial in a 3-month-old infant with transposition of the great vessels are reported.", "contents": "Heparinless, oxygenatorless perfusion rewarming following surface-induced deep hypothermia for open-heart surgery. To facilitate perfusion rewarming without the use of total body heparinization or an oxygenator following open-heart correction with surface hypothermia, we divised a pump circuit. The circuit, totally primed with 100 c.c. of saline, consists of polyurethane-polyvinyl-graphite (PPG) coated Tygon tubes (with one end tapered by heat treatment) and a copper-coil heat exchanger. A roller pump was used to achieve partial bypass from the left atrium to the ascending aorta with flow rates up to 70 c.c. per kilogram per minute. Experiments in dogs resulted in rapid rewarming, immediate return of cardiac function, and hematologic alterations similar to those noted during surface rewarming. The safety of the method was also demonstrated. Prothrombin time, partial thromboplastin time, and platelet values returned to control levels upon rewarming, and no thromboemboli or bleeding problems were noted. Six clinical experiences were accumulated. Details of the method, hematologic and blood chemical analyses in dogs, and the first clinical trial in a 3-month-old infant with transposition of the great vessels are reported."} {"id": "PMID:1263566", "title": "Methylprednisolone. Pharmacologic doses in shock lung syndrome.", "content": "Patients with shock lung syndrome were identified as those who developed acute respiratory failure after a profound episode of hypotension secondary to hemorrhagic, gram-negative, or endotoxic shock. In this study, each of the 10 patients with shock lung syndrome received methylprednisolone sodium succinate, 30 mg. per kilogram, intravenously every 6 hours for 48 hours. In addition, all patients were supported with mechanical ventilation, with or without positive end-expiratory pressure (PEEP). Arterial oxygenation improved markedly, and pulmonary edema resolved in all patients. Nine were discharged from the hospital and one died subsequently of disseminated intravascular coagulation. This study demonstrated a significant improvement in mortality rate with repeated pharmacologic doses of methylprednisolone compared to previously reported mortality rates of 60 to 90 per cent in patients with shock lung syndrome treated without repeated pharmacologic doses of steroid therapy.", "contents": "Methylprednisolone. Pharmacologic doses in shock lung syndrome. Patients with shock lung syndrome were identified as those who developed acute respiratory failure after a profound episode of hypotension secondary to hemorrhagic, gram-negative, or endotoxic shock. In this study, each of the 10 patients with shock lung syndrome received methylprednisolone sodium succinate, 30 mg. per kilogram, intravenously every 6 hours for 48 hours. In addition, all patients were supported with mechanical ventilation, with or without positive end-expiratory pressure (PEEP). Arterial oxygenation improved markedly, and pulmonary edema resolved in all patients. Nine were discharged from the hospital and one died subsequently of disseminated intravascular coagulation. This study demonstrated a significant improvement in mortality rate with repeated pharmacologic doses of methylprednisolone compared to previously reported mortality rates of 60 to 90 per cent in patients with shock lung syndrome treated without repeated pharmacologic doses of steroid therapy."} {"id": "PMID:1263567", "title": "A new instrument for the evaluation fo tissue tonicity in lymphoedema.", "content": "An instrument which measures the resistance of the tissues to compression has been used to assess the effectiveness of a therapy for long term lymphoedema. In this preliminary study, all cases of long standing lymphodema showed an increased resistance of the affected tissue to compression. Following an average of 30 months' Venalot treatment the resistance of the fibrotic tissues was restored to normal levels. It is believed that this way of assessing the state of the tissues and the value of therapy is a more accurate representation of the actual situation and should be used in preference to measurement of the circumference or plethysmography.", "contents": "A new instrument for the evaluation fo tissue tonicity in lymphoedema. An instrument which measures the resistance of the tissues to compression has been used to assess the effectiveness of a therapy for long term lymphoedema. In this preliminary study, all cases of long standing lymphodema showed an increased resistance of the affected tissue to compression. Following an average of 30 months' Venalot treatment the resistance of the fibrotic tissues was restored to normal levels. It is believed that this way of assessing the state of the tissues and the value of therapy is a more accurate representation of the actual situation and should be used in preference to measurement of the circumference or plethysmography."} {"id": "PMID:1263568", "title": "Role of lymphography in management of filarial chyluria.", "content": "1. One hundred patients with chyluria were studied with lymphography and 80 cases were followed up for a period varying between six months to two and one half years. 2. There was preponderance of left sided lesions. The site of fistulations were mostly in the region of pelvis and calyces of the kidney. 3. It was observed that lymphography was very useful in treatment of chyluria. Thirty-eight patients (48%) with chyluria were completely free from symptoms and after lymphography, 23 (28%) of them had relief and 19 (24%) of the patients did not have any beneficial effect after lymphography. This procedure was of great help in demonstrating the site of fistulations which could be surgically corrected, in certain situations. 4. Lymphographic appearances of thoracic duct was helpful in deciding the operation of thoracic duct jugular vein anastomosis in some cases. 5. Lymphatico venous anastomosis was done in 3 patients at the root of the scrotum in whom retrograde flow of contrast material occurred into the testicular lymphatics on lymphography.", "contents": "Role of lymphography in management of filarial chyluria. 1. One hundred patients with chyluria were studied with lymphography and 80 cases were followed up for a period varying between six months to two and one half years. 2. There was preponderance of left sided lesions. The site of fistulations were mostly in the region of pelvis and calyces of the kidney. 3. It was observed that lymphography was very useful in treatment of chyluria. Thirty-eight patients (48%) with chyluria were completely free from symptoms and after lymphography, 23 (28%) of them had relief and 19 (24%) of the patients did not have any beneficial effect after lymphography. This procedure was of great help in demonstrating the site of fistulations which could be surgically corrected, in certain situations. 4. Lymphographic appearances of thoracic duct was helpful in deciding the operation of thoracic duct jugular vein anastomosis in some cases. 5. Lymphatico venous anastomosis was done in 3 patients at the root of the scrotum in whom retrograde flow of contrast material occurred into the testicular lymphatics on lymphography."} {"id": "PMID:1263569", "title": "Lymphographic changes caused by lymph node metastases in carcinoma of the suprarenal glands.", "content": "In the literature reviewed, only two articles were found describing lymphographical changes caused by metastases of malignant adrenal tumours. A patient with anaplastic carcinoma of the suprarenal gland is presented here. In this patient, postoperative retroperitoneal lymphography with control films was of vital importance for the planning of post-operative treatment and follow-up.", "contents": "Lymphographic changes caused by lymph node metastases in carcinoma of the suprarenal glands. In the literature reviewed, only two articles were found describing lymphographical changes caused by metastases of malignant adrenal tumours. A patient with anaplastic carcinoma of the suprarenal gland is presented here. In this patient, postoperative retroperitoneal lymphography with control films was of vital importance for the planning of post-operative treatment and follow-up."} {"id": "PMID:1263571", "title": "Diffuse lymphangiomyomatosis.", "content": "A case of diffuse lymphangiomyomatosis with involvement of the large veins of the body is reported. The clinical, pathologoanatomic and especially the roentgenologic findings are described. Interstitial lung thickening, pleural effusions and spontaneous pneumothorax are findings which together with a stasis in the lymphatic system strongly suggest the diagnosis. The extensive involvement of the venous system supports the theory of a hamartomatous nature of the disease.", "contents": "Diffuse lymphangiomyomatosis. A case of diffuse lymphangiomyomatosis with involvement of the large veins of the body is reported. The clinical, pathologoanatomic and especially the roentgenologic findings are described. Interstitial lung thickening, pleural effusions and spontaneous pneumothorax are findings which together with a stasis in the lymphatic system strongly suggest the diagnosis. The extensive involvement of the venous system supports the theory of a hamartomatous nature of the disease."} {"id": "PMID:1263572", "title": "The lymph node in experimental xanthomatosis.", "content": "There is significant, progressive replacement of the lymphoid elements of the lymph node by foam cells in experimental xanthomatosis. These cells first form islands in the subcortical area. Subsequently they involve the medullary cords and finally, they replace the cortex. The xanthomata are higly vascular, consisting of a dense capillary network of samall and short capillaries. These newly visualized capillaries are fully integrated and incorporated in the normal blood supply of the lymph node. No significant distortion of the larger venules and arterioles were observed. It is noteworthy to observe the great capacity of the vascular supply of the lymph node in reacting to situations of significant enlargment and replacement of the lymphoid elements.", "contents": "The lymph node in experimental xanthomatosis. There is significant, progressive replacement of the lymphoid elements of the lymph node by foam cells in experimental xanthomatosis. These cells first form islands in the subcortical area. Subsequently they involve the medullary cords and finally, they replace the cortex. The xanthomata are higly vascular, consisting of a dense capillary network of samall and short capillaries. These newly visualized capillaries are fully integrated and incorporated in the normal blood supply of the lymph node. No significant distortion of the larger venules and arterioles were observed. It is noteworthy to observe the great capacity of the vascular supply of the lymph node in reacting to situations of significant enlargment and replacement of the lymphoid elements."} {"id": "PMID:1263573", "title": "Lymphocyte function in Hodgkin's Disease.", "content": "The immunologic deficiency of Hodgkin's disease includes skin anergy, delay in homograft rejection, negative transformation response of blood lymphocytes, and susceptibility to infections, particularly those of fungal or viral etiology (1, 3, 5). Since thymus-derived lymphocytes normally mediate these functions, a disturbance of this cell system would account for the observed immunological deficiencies in Hodgkin's disease. The majority, if not all of thymus-derived lymphocytes belong to the pool of recirculating, long-lived, small lymphocytes and an unimpeded circulation of these cells between lymph and blood is considered essential for a complete expression of their immunocompetence. Blockage and alteration of this circulation at the level of the lymph node is likely to occur in patients with Hodgkin's disease because of the characteristic infiltration of the lymph nodes by neoplastic cells. The question arises, therefore, whether the immunological deficiencies of Hodgkin's disease are due to intrinsically incompetent lymphocytes or the result of a faulty circulation of intrinsically competent lymphocytes. To answer this question the thoracic duct lymphocytes as well as blood lymphocytes of a patient with Hodgkin's disease have been studied with regard to re-circulation and immunocompetence.", "contents": "Lymphocyte function in Hodgkin's Disease. The immunologic deficiency of Hodgkin's disease includes skin anergy, delay in homograft rejection, negative transformation response of blood lymphocytes, and susceptibility to infections, particularly those of fungal or viral etiology (1, 3, 5). Since thymus-derived lymphocytes normally mediate these functions, a disturbance of this cell system would account for the observed immunological deficiencies in Hodgkin's disease. The majority, if not all of thymus-derived lymphocytes belong to the pool of recirculating, long-lived, small lymphocytes and an unimpeded circulation of these cells between lymph and blood is considered essential for a complete expression of their immunocompetence. Blockage and alteration of this circulation at the level of the lymph node is likely to occur in patients with Hodgkin's disease because of the characteristic infiltration of the lymph nodes by neoplastic cells. The question arises, therefore, whether the immunological deficiencies of Hodgkin's disease are due to intrinsically incompetent lymphocytes or the result of a faulty circulation of intrinsically competent lymphocytes. To answer this question the thoracic duct lymphocytes as well as blood lymphocytes of a patient with Hodgkin's disease have been studied with regard to re-circulation and immunocompetence."} {"id": "PMID:1263574", "title": "On radioactive labelling of the lymph drainage regions of the pelvis.", "content": "The introduction of radioisotopes in the surgical management of cervical carcinoma at our clinic in 1970 constituted a major advance in this respect. Prior to surgery the lymphatic tissue of the pelvic region is labelled by subcutaneous applications of radioisotopes. Our experience shows that the body's kinetics encourage the deposition of the radionucleide and thus visualization even of the groups of lymph nodes located in the deeper layers of the pelvic region. This method allows virtually complete lymphonodectomy with resultant improvement of cure rates.", "contents": "On radioactive labelling of the lymph drainage regions of the pelvis. The introduction of radioisotopes in the surgical management of cervical carcinoma at our clinic in 1970 constituted a major advance in this respect. Prior to surgery the lymphatic tissue of the pelvic region is labelled by subcutaneous applications of radioisotopes. Our experience shows that the body's kinetics encourage the deposition of the radionucleide and thus visualization even of the groups of lymph nodes located in the deeper layers of the pelvic region. This method allows virtually complete lymphonodectomy with resultant improvement of cure rates."} {"id": "PMID:1263575", "title": "A new derivation of average molecular weights of nonlinear polymers.", "content": "A new method for calculating average molecular weights is presented for nonlinear polymers. In contrast to the previous methods of Flory and Stockmayer which first calculate the distribution of all species and then use the distributions to calculate average properties, the new method calculates these properties directly. In contrast to the method of Gordon, probability generating functions are not required. Starting with elementary probability and utilizing the recursive nature of network polymers property relations can be developed more simply. We illustrate the method for calculations of Mw Mz, and the gel point for a wide variety of polyfunctional polymerizations.", "contents": "A new derivation of average molecular weights of nonlinear polymers. A new method for calculating average molecular weights is presented for nonlinear polymers. In contrast to the previous methods of Flory and Stockmayer which first calculate the distribution of all species and then use the distributions to calculate average properties, the new method calculates these properties directly. In contrast to the method of Gordon, probability generating functions are not required. Starting with elementary probability and utilizing the recursive nature of network polymers property relations can be developed more simply. We illustrate the method for calculations of Mw Mz, and the gel point for a wide variety of polyfunctional polymerizations."} {"id": "PMID:1263577", "title": "Intrachain reaction of a pair of reactive groups attached to polymer ends. II. Monte carlo study on the intrachain reaction proceeding on trans/cis-polysarcosine chain.", "content": "Monte Carlo calculation was performed to evaluate the ring-closure probability of short polysarcosine chains. Calculations were made for unperturbed trans- non-self-intersecting trans-, and non-self-intersecting trans- and non-self-intersecting trans/cis-polysarcosine chains. In the latter case, the main chain amide bond was allowed to take cis as well as trans conformations. The ring-closure probability for unperturbed trans-polysarcosine chains was found to be substantially greater than for non-self-intersecting trans chains. Virtually no difference was observed between the ring-closure probability was used to estimate the cyclization constant, i.e., the ratio of rate constant for the intramolecular reaction of the two groups attached to the polymer ends to that of the intermolecular one. The results were compared with the experimental data for the intrachain reaction proceeding on polysarcosine chain reported in the first paper of this series. The Monte Carlo results roughly reproduced the experimental data and the calculated chain length dependence was consistent with the observed one for longer chains.", "contents": "Intrachain reaction of a pair of reactive groups attached to polymer ends. II. Monte carlo study on the intrachain reaction proceeding on trans/cis-polysarcosine chain. Monte Carlo calculation was performed to evaluate the ring-closure probability of short polysarcosine chains. Calculations were made for unperturbed trans- non-self-intersecting trans-, and non-self-intersecting trans- and non-self-intersecting trans/cis-polysarcosine chains. In the latter case, the main chain amide bond was allowed to take cis as well as trans conformations. The ring-closure probability for unperturbed trans-polysarcosine chains was found to be substantially greater than for non-self-intersecting trans chains. Virtually no difference was observed between the ring-closure probability was used to estimate the cyclization constant, i.e., the ratio of rate constant for the intramolecular reaction of the two groups attached to the polymer ends to that of the intermolecular one. The results were compared with the experimental data for the intrachain reaction proceeding on polysarcosine chain reported in the first paper of this series. The Monte Carlo results roughly reproduced the experimental data and the calculated chain length dependence was consistent with the observed one for longer chains."} {"id": "PMID:1263576", "title": "Determination of the structure of cellulose II.", "content": "The structure of regenerated cellulose is shown by x-ray diffraction to be comprised of an array of antiparallel chain molecules. The determination was based on the intensity data from rayon fibers and utilized rigid-body least-squares refinement techniques. The unit cell is monoclinic with space group P2(1) and dimensions a = 8.01 A, b = 9.04 A, c = 10.36 A (fiber axis), and gamma = 117.1 degrees. Models containing chains with the same sense (parallel) or alternating sense (antiparallel) were refined against the intensity data. The only acceptable model contains antiparallel chains. The -CH2OH groups of the corner chain are oriented near to the gt position while those of the center chain are near to the tg position. Both chains possess an O3-H-O5' intramolecular hydrogen bond, and the center chain also has an O2'-H-O6 intramolecular bond. Intermolecular hydrogen bonding occurs along the 020 planes (o6-h-o2 bonds for the corner chains and O6-H-O3 bonds for the center chains) and also along the 110 planes with a hydrogen bond between the O2-H of the corner chain and the O2' of the center chain. This center-corner chain hydrogen bonding is a major difference between the native and regenerated structures and may account for the stability of the latter form.", "contents": "Determination of the structure of cellulose II. The structure of regenerated cellulose is shown by x-ray diffraction to be comprised of an array of antiparallel chain molecules. The determination was based on the intensity data from rayon fibers and utilized rigid-body least-squares refinement techniques. The unit cell is monoclinic with space group P2(1) and dimensions a = 8.01 A, b = 9.04 A, c = 10.36 A (fiber axis), and gamma = 117.1 degrees. Models containing chains with the same sense (parallel) or alternating sense (antiparallel) were refined against the intensity data. The only acceptable model contains antiparallel chains. The -CH2OH groups of the corner chain are oriented near to the gt position while those of the center chain are near to the tg position. Both chains possess an O3-H-O5' intramolecular hydrogen bond, and the center chain also has an O2'-H-O6 intramolecular bond. Intermolecular hydrogen bonding occurs along the 020 planes (o6-h-o2 bonds for the corner chains and O6-H-O3 bonds for the center chains) and also along the 110 planes with a hydrogen bond between the O2-H of the corner chain and the O2' of the center chain. This center-corner chain hydrogen bonding is a major difference between the native and regenerated structures and may account for the stability of the latter form."} {"id": "PMID:1263591", "title": "The role of the deep femoral artery in revascularization of the lower extremity.", "content": "The deep femoral artery is often peculiarly resistant to atherosclerosis when the common and superficial femoral arteries are severly affected. At the Mayo Clinic between 1964 and 1972, 43 patients had aorta-deep femoral artery bypass as the definitive revascularization procedure for arteriel insufficiency of the lower extremities. Of the patients with grade 1 ischemia, 82% became asymptomatic as did 44% of those with grade 2 ischemia and 43% of those with ulceration and incipient gangrene. After 2 years, 25 of 40 (62%) previously symptomatic lower extremities had remained asymptomatic (in 31 patients available for follow-up evaluation). The rates were 68% and 55% after 3 and 4 years, respectively.", "contents": "The role of the deep femoral artery in revascularization of the lower extremity. The deep femoral artery is often peculiarly resistant to atherosclerosis when the common and superficial femoral arteries are severly affected. At the Mayo Clinic between 1964 and 1972, 43 patients had aorta-deep femoral artery bypass as the definitive revascularization procedure for arteriel insufficiency of the lower extremities. Of the patients with grade 1 ischemia, 82% became asymptomatic as did 44% of those with grade 2 ischemia and 43% of those with ulceration and incipient gangrene. After 2 years, 25 of 40 (62%) previously symptomatic lower extremities had remained asymptomatic (in 31 patients available for follow-up evaluation). The rates were 68% and 55% after 3 and 4 years, respectively."} {"id": "PMID:1263592", "title": "Skin fibrinolytic activity in cutaneous and systemic vasculitis.", "content": "Study of involved and uninvolved skin from patients with necrotizing vasculitis revealed diminished tissue fibrinolytic activity deposition of immunoreactants in involved skin. In these patients, the depletion of tissue fibrinolytic activity is probably the result of vessel injury secondary to the local deposit of immunoreactants. In addition, there was diminished tissue fibrinolytic activity in uninvolved skin from patients with and without clinical skin involvement, unassociated with the deposition of immunoreactants. The precise mechanism for diminished tissue lytic activity in these latter patients is not known, but it may be associated with generalized activation of the coagulation and fibrinolytic mechanisms that result in local depletion of tissue fibrinolytic activity. These local changes may aggravate the clinical course of the disease as well as inhibit the healing of the lesions.", "contents": "Skin fibrinolytic activity in cutaneous and systemic vasculitis. Study of involved and uninvolved skin from patients with necrotizing vasculitis revealed diminished tissue fibrinolytic activity deposition of immunoreactants in involved skin. In these patients, the depletion of tissue fibrinolytic activity is probably the result of vessel injury secondary to the local deposit of immunoreactants. In addition, there was diminished tissue fibrinolytic activity in uninvolved skin from patients with and without clinical skin involvement, unassociated with the deposition of immunoreactants. The precise mechanism for diminished tissue lytic activity in these latter patients is not known, but it may be associated with generalized activation of the coagulation and fibrinolytic mechanisms that result in local depletion of tissue fibrinolytic activity. These local changes may aggravate the clinical course of the disease as well as inhibit the healing of the lesions."} {"id": "PMID:1263593", "title": "Gastrocolic fistula complicating benign unoperated gastric ulcer. Report of four cases and review of the literature.", "content": "Of 957 patients undergoing operation for benign gastric ulcer and its complications from 1965 through June 1975, 90 had perforated ulcers. Among these were four patients in whom a gastrocolic fistula had formed. Although two of the four patients had symptoms due to peptic ulcer dating back 12 and 68 months, symptoms of a gastrocolic fistula were the initial presentation of ulcer disease in the other two. All four patients had watery diarrhea and weight loss, and barium enema examination was diagnostic in each case. The perforating ulcers were located in the distal stomach on the greater curvature in all four patients. Although enterostasis was not present in these cases, regurgitation of colonic contents probably results in bacterial overgrowth in the small intestine, causing structural and functional damage to the mucosal cells by bacterial products, manifested clinically by diarrhea in 75% of the patients. Surgery should be advised in all cases after adequate preparation of the patient; bowel preparation with cathartics, enemas, and oral antibiotics is mandatory. The preferred operation is one-stage enbloc hemigastrectomy and resection of the involved segment of colon along with the fistulous tract. The present series brings to 43 the total number of cases of gastrocolic fistulas complicating benign, previously unoperated gastric or duodenal ulcers. There is an appreciable mortality associated with this condition - 7 of these 43 patients (16%) died as a direct consequence of their fistula.", "contents": "Gastrocolic fistula complicating benign unoperated gastric ulcer. Report of four cases and review of the literature. Of 957 patients undergoing operation for benign gastric ulcer and its complications from 1965 through June 1975, 90 had perforated ulcers. Among these were four patients in whom a gastrocolic fistula had formed. Although two of the four patients had symptoms due to peptic ulcer dating back 12 and 68 months, symptoms of a gastrocolic fistula were the initial presentation of ulcer disease in the other two. All four patients had watery diarrhea and weight loss, and barium enema examination was diagnostic in each case. The perforating ulcers were located in the distal stomach on the greater curvature in all four patients. Although enterostasis was not present in these cases, regurgitation of colonic contents probably results in bacterial overgrowth in the small intestine, causing structural and functional damage to the mucosal cells by bacterial products, manifested clinically by diarrhea in 75% of the patients. Surgery should be advised in all cases after adequate preparation of the patient; bowel preparation with cathartics, enemas, and oral antibiotics is mandatory. The preferred operation is one-stage enbloc hemigastrectomy and resection of the involved segment of colon along with the fistulous tract. The present series brings to 43 the total number of cases of gastrocolic fistulas complicating benign, previously unoperated gastric or duodenal ulcers. There is an appreciable mortality associated with this condition - 7 of these 43 patients (16%) died as a direct consequence of their fistula."} {"id": "PMID:1263594", "title": "One-year graduated exercise program for men with angina pectoris. Evaluation by physiologic studies and coronary arteriography.", "content": "Eight men, 45 to 50 years of age, with mild stable angina pectoris, participated in a graduated exercise program. Coronary arteriography, left ventriculography, left ventricular hemodynamics at rest and during supine leg exercise, treadmill testing with electrocardiographic monitoring, and measurement of oxygen uptake were obtained before and 1 year after the exercise training program. No change was noted in the arteriographic appearance of coronary artery lesions or of collateral circulation. Left ventricular performance, assessed by qualitative left ventriculography and the hemodynamic response of the left ventricle to supine leg exercise, was unchanged after the training program. Oxygen consumption for a given repetitive work load during treadmill exercise decreased. Two patients with a pretraining exercise ECG positive for ischemia reverted to a normal response after the exercise program. All had a decrease in angina, an increase in self-esteem, and a more positive attitude toward their work and their disability.", "contents": "One-year graduated exercise program for men with angina pectoris. Evaluation by physiologic studies and coronary arteriography. Eight men, 45 to 50 years of age, with mild stable angina pectoris, participated in a graduated exercise program. Coronary arteriography, left ventriculography, left ventricular hemodynamics at rest and during supine leg exercise, treadmill testing with electrocardiographic monitoring, and measurement of oxygen uptake were obtained before and 1 year after the exercise training program. No change was noted in the arteriographic appearance of coronary artery lesions or of collateral circulation. Left ventricular performance, assessed by qualitative left ventriculography and the hemodynamic response of the left ventricle to supine leg exercise, was unchanged after the training program. Oxygen consumption for a given repetitive work load during treadmill exercise decreased. Two patients with a pretraining exercise ECG positive for ischemia reverted to a normal response after the exercise program. All had a decrease in angina, an increase in self-esteem, and a more positive attitude toward their work and their disability."} {"id": "PMID:1263595", "title": "The in vitro spectrum of the cephalosporins.", "content": "The cephalosporins may currently be classified according to their relative susceptibility to beta-lactamases. Cefoxitin, cefamandole, cefatrizine, and cephanone are relatively resistant to the gram-negative beta-lactamases, whereas cephalothin, cefamandole, and cefoxitin are resistant to staphylococcal beta-lactamase. Although the inhibitory activity of cephalothin is representative of that of cephaloridine, cephalexin, cefazolin, cephapirin, cephacetrile, and cephradine, there are significant differences between its activity and that of cefoxitin, cefamandole, and cefatrizine, especially against Enterobacter, Serratia, indole-positive Proteeae, Bacteroides fragilis, and ampicillin-resistant Haemophilus influenzae.", "contents": "The in vitro spectrum of the cephalosporins. The cephalosporins may currently be classified according to their relative susceptibility to beta-lactamases. Cefoxitin, cefamandole, cefatrizine, and cephanone are relatively resistant to the gram-negative beta-lactamases, whereas cephalothin, cefamandole, and cefoxitin are resistant to staphylococcal beta-lactamase. Although the inhibitory activity of cephalothin is representative of that of cephaloridine, cephalexin, cefazolin, cephapirin, cephacetrile, and cephradine, there are significant differences between its activity and that of cefoxitin, cefamandole, and cefatrizine, especially against Enterobacter, Serratia, indole-positive Proteeae, Bacteroides fragilis, and ampicillin-resistant Haemophilus influenzae."} {"id": "PMID:1263596", "title": "Persistent Nausea without organic cause.", "content": "The onset of functional nausea among 77 patients was frequently related to an organic disease or to a psychophysiologic response to stress. Later, the nausea had obvious features of conversion, hypochondriasis, or an hallucination. The patients had significant psychiatric disorders as assessed by the Minnesota Multiphasic Personality Inventory (MMPI) and by clinical examination. While in the hospital most patients experienced symptomatic improvement but they did not accept a psychologic explanation for their nausea.", "contents": "Persistent Nausea without organic cause. The onset of functional nausea among 77 patients was frequently related to an organic disease or to a psychophysiologic response to stress. Later, the nausea had obvious features of conversion, hypochondriasis, or an hallucination. The patients had significant psychiatric disorders as assessed by the Minnesota Multiphasic Personality Inventory (MMPI) and by clinical examination. While in the hospital most patients experienced symptomatic improvement but they did not accept a psychologic explanation for their nausea."} {"id": "PMID:1263598", "title": "The electroencephalogram in pernicious anemia.", "content": "EEGs were recorded in 54 patients with pernicious anemia. Six patients without nervous system involvement had normal EEGs, 10 patients with spinal cord or peripheral nervous system involvement had normal or minimally abnormal EEGs, 17 of 19 patients with evidence of mental dysfunction had abnormal EEGs with the most consistent finding being an excess of theta slowing, and 19 patients with pernicious anemia and other neurologic diseases showed EEG findings reflecting the complicating disease process. In general, the EEG abnormalities in patients with pernicious anemia correlated well with the presence of cerebral dysfunction but not with the degree of anemia. The EEG was also a good indicator for detecting and confirming other intracranial disease processes unrelated to pernicious anemia.", "contents": "The electroencephalogram in pernicious anemia. EEGs were recorded in 54 patients with pernicious anemia. Six patients without nervous system involvement had normal EEGs, 10 patients with spinal cord or peripheral nervous system involvement had normal or minimally abnormal EEGs, 17 of 19 patients with evidence of mental dysfunction had abnormal EEGs with the most consistent finding being an excess of theta slowing, and 19 patients with pernicious anemia and other neurologic diseases showed EEG findings reflecting the complicating disease process. In general, the EEG abnormalities in patients with pernicious anemia correlated well with the presence of cerebral dysfunction but not with the degree of anemia. The EEG was also a good indicator for detecting and confirming other intracranial disease processes unrelated to pernicious anemia."} {"id": "PMID:1263599", "title": "Normal renal function: CIN and CPAH in healthy donors before and after nephrectomy.", "content": "To establish normal values for glomerular filtration rate and effective renal plasma flow for age and sex, the records of 141 healthy renal transplant donors were reviewed. These patients had no history of renal or systemic disease, had normal physical examinations, and had normal laboratory studies in addition to having studies of the clearances of insulin (Cin) and para-amino hippurate (Cpah) preoperatively. Regression analysis of the clearance data revealed no significant sex differences in renal function. A linear age-related decline in renal function begins in the 20's and decreases by 4 ml/min per decade for Cin and by 35 ml/min per decade for Cpah through the 60's, our oldest patients studied; therefore, the absolute lower limits of normal (lower fifth percentile) for Cin and Cpah were calculated as a function of age. Residual function was constant with average postoperative clearances 70% of preoperative values regardless of age.", "contents": "Normal renal function: CIN and CPAH in healthy donors before and after nephrectomy. To establish normal values for glomerular filtration rate and effective renal plasma flow for age and sex, the records of 141 healthy renal transplant donors were reviewed. These patients had no history of renal or systemic disease, had normal physical examinations, and had normal laboratory studies in addition to having studies of the clearances of insulin (Cin) and para-amino hippurate (Cpah) preoperatively. Regression analysis of the clearance data revealed no significant sex differences in renal function. A linear age-related decline in renal function begins in the 20's and decreases by 4 ml/min per decade for Cin and by 35 ml/min per decade for Cpah through the 60's, our oldest patients studied; therefore, the absolute lower limits of normal (lower fifth percentile) for Cin and Cpah were calculated as a function of age. Residual function was constant with average postoperative clearances 70% of preoperative values regardless of age."} {"id": "PMID:1263600", "title": "Neurovascular microsurgery: a model for laboratory investigation and the development of technical skills.", "content": "An inexpensive and reproducible model to help in developing the technical skills for, and to investigate experimentally, a microvascular anastomosis resembling the superficial temporal-middle cerebral artery bypass is described. The model is used to illustrate the important principles of microvascular surgery. Using a standardized operative technique, we evaluated 50 successive preparations by perfusion; the patency rate was 100%.", "contents": "Neurovascular microsurgery: a model for laboratory investigation and the development of technical skills. An inexpensive and reproducible model to help in developing the technical skills for, and to investigate experimentally, a microvascular anastomosis resembling the superficial temporal-middle cerebral artery bypass is described. The model is used to illustrate the important principles of microvascular surgery. Using a standardized operative technique, we evaluated 50 successive preparations by perfusion; the patency rate was 100%."} {"id": "PMID:1263601", "title": "Echocardiographic observations in a patient with acute myocardial infarction with a nondiagnostic electrocardiogram.", "content": "Echocardiography revealed a persistent large segment of dyskinesis of the posterolateral wall in a patient with clinical an enzyme evidence of acute myocardial infarction but without diagnostic electrocardiographic changes. A left ventricular angiogram confirmed the echocardiographic findings.", "contents": "Echocardiographic observations in a patient with acute myocardial infarction with a nondiagnostic electrocardiogram. Echocardiography revealed a persistent large segment of dyskinesis of the posterolateral wall in a patient with clinical an enzyme evidence of acute myocardial infarction but without diagnostic electrocardiographic changes. A left ventricular angiogram confirmed the echocardiographic findings."} {"id": "PMID:1263610", "title": "Cytotoxic effects on the plasma membrane of human diploid fibroblasts--a comparative study of leakage tests.", "content": "Confluent monolayers of human diploid lung fibroblasts were treated with cytolytic agents. The induced membrane damage was investigated by different test systems. Changes of membrane permeability were compared with morphological alterations. Four tests employed leakage of cytoplasmic markers of different sizes as criteria of membrane damage. Radioactive markers of the following decreasing size order were used: [3H]RNA (MW greater than 200,000) greater than 51Cr greater than [3H]nucleotides greater than [1-14C]alpha-amino-isobutyric acid (AIB, MW 103). Uptake of trypan blue was employed as a fifth criterior of changed membrane permeability. A comparison between the tests indicated the following order of sensitivity for detection of membrane damage: leakage of AIB-label greater than leakage of nucleotide label greater than leakage of 51Cr-label=uptake of trypan blue= morphological changes greater than leakage of RNA-label. Two distinct types of leakage patterns were evident: 1. Upon incubation with Triton X-100 all four release curves coincided. This was considered as representing large functional \"holes\". 2. With the polyene amphotericin B the smallest marker (AIB) was released to a strikingly greater extent than other markers. This was regarded as representing very small functional \"holes\". Melittin from bee venom and theta-toxin from Clostridium perfringens induced leakage patterns of two intermediate types. The results indicate that a combination of several different size markers may be useful for characterizing induced membrane lesions.", "contents": "Cytotoxic effects on the plasma membrane of human diploid fibroblasts--a comparative study of leakage tests. Confluent monolayers of human diploid lung fibroblasts were treated with cytolytic agents. The induced membrane damage was investigated by different test systems. Changes of membrane permeability were compared with morphological alterations. Four tests employed leakage of cytoplasmic markers of different sizes as criteria of membrane damage. Radioactive markers of the following decreasing size order were used: [3H]RNA (MW greater than 200,000) greater than 51Cr greater than [3H]nucleotides greater than [1-14C]alpha-amino-isobutyric acid (AIB, MW 103). Uptake of trypan blue was employed as a fifth criterior of changed membrane permeability. A comparison between the tests indicated the following order of sensitivity for detection of membrane damage: leakage of AIB-label greater than leakage of nucleotide label greater than leakage of 51Cr-label=uptake of trypan blue= morphological changes greater than leakage of RNA-label. Two distinct types of leakage patterns were evident: 1. Upon incubation with Triton X-100 all four release curves coincided. This was considered as representing large functional \"holes\". 2. With the polyene amphotericin B the smallest marker (AIB) was released to a strikingly greater extent than other markers. This was regarded as representing very small functional \"holes\". Melittin from bee venom and theta-toxin from Clostridium perfringens induced leakage patterns of two intermediate types. The results indicate that a combination of several different size markers may be useful for characterizing induced membrane lesions."} {"id": "PMID:1263606", "title": "Changes in ribonuclease with age in the fungus Rhizoctonia solani.", "content": "The enzyme ribonuclease (RNase) which was isolated from Rhizoctonia solani Kuehn degraded ribonucleic acid from both Torula yeast and from Rhizoctonia solani mycelia. As the Rhizoctonia mycelia aged, there was an increase in both the total and the specific activities of the RNase present in the mycelia. This change is discussed in relation to the age dependent decrease in protein synthesis in this fungus.", "contents": "Changes in ribonuclease with age in the fungus Rhizoctonia solani. The enzyme ribonuclease (RNase) which was isolated from Rhizoctonia solani Kuehn degraded ribonucleic acid from both Torula yeast and from Rhizoctonia solani mycelia. As the Rhizoctonia mycelia aged, there was an increase in both the total and the specific activities of the RNase present in the mycelia. This change is discussed in relation to the age dependent decrease in protein synthesis in this fungus."} {"id": "PMID:1263608", "title": "Relationship between cell replication and volume in senescent human diploid fibroblasts.", "content": "Since alterations in cell replication rate and cell volume distribution are two of the earliest changes seen in the culture of human diploid cells, it was decided to examine the relationship between these parameters. After standardization of the conditions for cell volume measurements (enzyme treatment, temperature and stage of cell growth), a close correlation was observed between cell population doubling time and cell volume in WI-38 cells at various levels of in vitro passage. Cell populations which replicate more slowly (trisomic-21 fibroblasts, fetal skin fibroblasts) also demonstrated a shift to larger cell volumes when compared with control rapidly replicating cell populations at the same level of in vitro passage. Similar shifts to larger cell volumes were produced by reducing serum concentration, decreasing incubation temperature and inhibiting DNA synthesis. Separation of senescent WI-38 cells on the basis of cell volume revealed that the cell fractions with the largest modal cell volume contained the highest percentage of slow or nonreplicating cells. Therefore, an inverse relationship appears to exist between growth rate and cell volume in cultured human diploid fibroblasts.", "contents": "Relationship between cell replication and volume in senescent human diploid fibroblasts. Since alterations in cell replication rate and cell volume distribution are two of the earliest changes seen in the culture of human diploid cells, it was decided to examine the relationship between these parameters. After standardization of the conditions for cell volume measurements (enzyme treatment, temperature and stage of cell growth), a close correlation was observed between cell population doubling time and cell volume in WI-38 cells at various levels of in vitro passage. Cell populations which replicate more slowly (trisomic-21 fibroblasts, fetal skin fibroblasts) also demonstrated a shift to larger cell volumes when compared with control rapidly replicating cell populations at the same level of in vitro passage. Similar shifts to larger cell volumes were produced by reducing serum concentration, decreasing incubation temperature and inhibiting DNA synthesis. Separation of senescent WI-38 cells on the basis of cell volume revealed that the cell fractions with the largest modal cell volume contained the highest percentage of slow or nonreplicating cells. Therefore, an inverse relationship appears to exist between growth rate and cell volume in cultured human diploid fibroblasts."} {"id": "PMID:1263609", "title": "DNA repair in late-passage human cells.", "content": "Monolayer cultures of WI-38 cells from passages 18 to 60 were exposed to ultraviolet radiation, or to N-acetoxy-AAF, or to gamma-rays. The cultures were incubated in 3H-dThd, and unscheduled DNA synthesis--a measure of DNA repair--was measured radioautographically. Late passage cultures showed less repair, and many cells showed none. Double-label radioautographs indicated that there is an excellent correlation between cells that do scheduled synthesis and cells that do unscheduled synthesis. We interpret our results as indicating that failure of repair is not a causal event in the failure of late passage cells to divide, but that as cells age the ability to do the many coordinated steps in repair declines.", "contents": "DNA repair in late-passage human cells. Monolayer cultures of WI-38 cells from passages 18 to 60 were exposed to ultraviolet radiation, or to N-acetoxy-AAF, or to gamma-rays. The cultures were incubated in 3H-dThd, and unscheduled DNA synthesis--a measure of DNA repair--was measured radioautographically. Late passage cultures showed less repair, and many cells showed none. Double-label radioautographs indicated that there is an excellent correlation between cells that do scheduled synthesis and cells that do unscheduled synthesis. We interpret our results as indicating that failure of repair is not a causal event in the failure of late passage cells to divide, but that as cells age the ability to do the many coordinated steps in repair declines."} {"id": "PMID:1263605", "title": "Decrease in the number of synapses in the senescent brain: a quantitative electron microscopic analysis of the dentate gyrus molecular layer in the rat.", "content": "Axo-dendritic synapses were counted in electron micrographs taken from the middle third of the dentate gyrus molecular layer of young adult and senescent Fischer 344 rats. A significant decrease in the number of synapses was found in senescent animals relative to young ones. This loss of synapses, which involved all the morphological varieties of axo-dendritic synaptic contacts in the dentate gyrus molecular layer, appeared to be unrelated to changes in dimensions of synapses, tissue volume or number of postsynaptic granule cells. It is proposed that the age-related loss of synaptic contacts might be attributed to a reduced capacity of senescent brains for synaptic regeneration and remodelling.", "contents": "Decrease in the number of synapses in the senescent brain: a quantitative electron microscopic analysis of the dentate gyrus molecular layer in the rat. Axo-dendritic synapses were counted in electron micrographs taken from the middle third of the dentate gyrus molecular layer of young adult and senescent Fischer 344 rats. A significant decrease in the number of synapses was found in senescent animals relative to young ones. This loss of synapses, which involved all the morphological varieties of axo-dendritic synaptic contacts in the dentate gyrus molecular layer, appeared to be unrelated to changes in dimensions of synapses, tissue volume or number of postsynaptic granule cells. It is proposed that the age-related loss of synaptic contacts might be attributed to a reduced capacity of senescent brains for synaptic regeneration and remodelling."} {"id": "PMID:1263607", "title": "Ovarian development in athymic nude mice. III. The effect of PMSG and oestradiol upon the size and composition of the ovarian follicle population.", "content": "The response of 1 month old congenitally athymic nude mice and their phenotypically normal littermates to exogenous pregnant mare serum gonadotrophin (PMSG) and oestradiol-17beta has been tested. An equal increase in the number of growing follicles was detected in both nudes and controls in response to PMSG. A specific increase occurred in the number of unilaminar follicles in the initial growth stages in addition to the increase in the number of multilaminar and vesicular follicles. Oestradiol depressed follicular growth equally in both nudes and controls. The contracted appearance of growing follicles in nudes disappeared under the influence of PMSG and was induced in ovaries of control mice treated with oestradiol. We conclude that the ability of the mouse ovary to respond to exogenous PMSG and the oestradiol is not impaired by congenital athymia as expressed in the nude genotype. The data suggest that the retardation of follicular growth already reported in 1 month old nudes arises from a deficiency of gonadotrophin.", "contents": "Ovarian development in athymic nude mice. III. The effect of PMSG and oestradiol upon the size and composition of the ovarian follicle population. The response of 1 month old congenitally athymic nude mice and their phenotypically normal littermates to exogenous pregnant mare serum gonadotrophin (PMSG) and oestradiol-17beta has been tested. An equal increase in the number of growing follicles was detected in both nudes and controls in response to PMSG. A specific increase occurred in the number of unilaminar follicles in the initial growth stages in addition to the increase in the number of multilaminar and vesicular follicles. Oestradiol depressed follicular growth equally in both nudes and controls. The contracted appearance of growing follicles in nudes disappeared under the influence of PMSG and was induced in ovaries of control mice treated with oestradiol. We conclude that the ability of the mouse ovary to respond to exogenous PMSG and the oestradiol is not impaired by congenital athymia as expressed in the nude genotype. The data suggest that the retardation of follicular growth already reported in 1 month old nudes arises from a deficiency of gonadotrophin."} {"id": "PMID:1263620", "title": "The performance of merging hospitals.", "content": "The primary aim of this paper is to examine the impact of mergers on the performance of hospitals. The study tests the null hypothesis that no significant differences exist in efficiency and effectiveness between hospitals that merge and those which remain independent entities. The performance evaluation model follows closely similar models used to study the performance of merging banks. The findings of the study suggest that 1) large urban hospitals contemplating merger should view carefully the trade-offs involved between efficiency and effectiveness as indicated by the measures employed in this study, since the evidence indicates that the increased service capability achieved in merging hospitals is accompanied by a significant increase in costs; and 2) the concept appears very promising for small rural hospitals, especially in veiw of evidence that various benefits extend over the short-, intermediate-, and long-range time frames employed in the study.", "contents": "The performance of merging hospitals. The primary aim of this paper is to examine the impact of mergers on the performance of hospitals. The study tests the null hypothesis that no significant differences exist in efficiency and effectiveness between hospitals that merge and those which remain independent entities. The performance evaluation model follows closely similar models used to study the performance of merging banks. The findings of the study suggest that 1) large urban hospitals contemplating merger should view carefully the trade-offs involved between efficiency and effectiveness as indicated by the measures employed in this study, since the evidence indicates that the increased service capability achieved in merging hospitals is accompanied by a significant increase in costs; and 2) the concept appears very promising for small rural hospitals, especially in veiw of evidence that various benefits extend over the short-, intermediate-, and long-range time frames employed in the study."} {"id": "PMID:1263621", "title": "Health information system installation: principles and problems.", "content": "Many studies have been done to identify health problems and practices and to obtain knowledge of the characteristics of the population. Often specific data desired by the investigators are not available at the time of final analysis. This paper emphasizes the importance of planning and designing the system for recording and processing information together with the planning and development of the program or project. Principles that were applied and problems that occurred in demonstration projects in developed and less developed countries are described. Some examples of applications to improve the health services for the rural dewellers in a less developed country are illustrated. The methodology evolved has broad application and may be useful to others who have needs for data on an ambulatory population.", "contents": "Health information system installation: principles and problems. Many studies have been done to identify health problems and practices and to obtain knowledge of the characteristics of the population. Often specific data desired by the investigators are not available at the time of final analysis. This paper emphasizes the importance of planning and designing the system for recording and processing information together with the planning and development of the program or project. Principles that were applied and problems that occurred in demonstration projects in developed and less developed countries are described. Some examples of applications to improve the health services for the rural dewellers in a less developed country are illustrated. The methodology evolved has broad application and may be useful to others who have needs for data on an ambulatory population."} {"id": "PMID:1263622", "title": "Modeling health services systems.", "content": "A conceptual model for the analysis of personal and collective health services systems is proposed. By placing existing formal models in the framework of this conceptual model, we emphasized their qualities and shortcomings. We discussed the normative and descriptive approach of formal modeling. Finally we emphasized the close conceptual parallel that exists between personal and collective health services systems.", "contents": "Modeling health services systems. A conceptual model for the analysis of personal and collective health services systems is proposed. By placing existing formal models in the framework of this conceptual model, we emphasized their qualities and shortcomings. We discussed the normative and descriptive approach of formal modeling. Finally we emphasized the close conceptual parallel that exists between personal and collective health services systems."} {"id": "PMID:1263623", "title": "The recipients and results of acupuncture.", "content": "A private clinic was established in Los Angeles in late 1972 to perform acupuncture. Most individuals seeking treatment were middle-aged and well educated. All had considerable experience with traditional medical care for their problem. The principal reason for seeking care was relief from chronic pain. Thirteen per cent had received other nontraditional forms of therapy; over one-third indicated that they sought acupuncture as a \"last resort.\" The results of certain psychological tests taken by these patients were within the range of normal. On completion of six or more treatments, 74 per cent said they had been helped; 54 per cent of those followed for three months and 24 per cent contacted one year later were improved. A subgroup of patients who received only temporary improvement had significantly different scores on psychological scales suggesting the results noted in this group may have been due to a \"placebo\" effect. A significant proportion of those who dropped out of treatment did so because they had achieved the desired benefits.", "contents": "The recipients and results of acupuncture. A private clinic was established in Los Angeles in late 1972 to perform acupuncture. Most individuals seeking treatment were middle-aged and well educated. All had considerable experience with traditional medical care for their problem. The principal reason for seeking care was relief from chronic pain. Thirteen per cent had received other nontraditional forms of therapy; over one-third indicated that they sought acupuncture as a \"last resort.\" The results of certain psychological tests taken by these patients were within the range of normal. On completion of six or more treatments, 74 per cent said they had been helped; 54 per cent of those followed for three months and 24 per cent contacted one year later were improved. A subgroup of patients who received only temporary improvement had significantly different scores on psychological scales suggesting the results noted in this group may have been due to a \"placebo\" effect. A significant proportion of those who dropped out of treatment did so because they had achieved the desired benefits."} {"id": "PMID:1263624", "title": "Mailed versus telephoned appointment reminders to reduce broken appointments in a hospital outpatient department.", "content": "This study compared mail, telephone, and control strategies to reduce the rate of broken appointments in a pediatric outpatient department. Based on 1,039 randomly assigned appointments, the mail strategy had a broken appointment rate of 29.1 per cent, the telephone strategy of 25.3 per cent, and the control of 44.2 per cent. Both strategies were significantly effective, but the difference between them was not significant. Patients without telephones had a higher rate of broken appointments than patients with telephones. Mailed reminders are the more cost-effective intervention.", "contents": "Mailed versus telephoned appointment reminders to reduce broken appointments in a hospital outpatient department. This study compared mail, telephone, and control strategies to reduce the rate of broken appointments in a pediatric outpatient department. Based on 1,039 randomly assigned appointments, the mail strategy had a broken appointment rate of 29.1 per cent, the telephone strategy of 25.3 per cent, and the control of 44.2 per cent. Both strategies were significantly effective, but the difference between them was not significant. Patients without telephones had a higher rate of broken appointments than patients with telephones. Mailed reminders are the more cost-effective intervention."} {"id": "PMID:1263625", "title": "Consumer participation and social accountability.", "content": "Consumer participation in the planning and management of health care programs is prescribed as a method for increasing provider responsiveness to the goals and needs of users of services. However, issues related to the nature of mandates to implement consumer participation has not had the impact on policy development proposed for it. While structural changes can be identified which might enhance the consumer role in decision making, it will also be necessary for the consumer sector to develop a strategy which will prompt major rather than incremental movement.", "contents": "Consumer participation and social accountability. Consumer participation in the planning and management of health care programs is prescribed as a method for increasing provider responsiveness to the goals and needs of users of services. However, issues related to the nature of mandates to implement consumer participation has not had the impact on policy development proposed for it. While structural changes can be identified which might enhance the consumer role in decision making, it will also be necessary for the consumer sector to develop a strategy which will prompt major rather than incremental movement."} {"id": "PMID:1263626", "title": "Office records in the evaluation of quality of care.", "content": "Trained reviewers audited 10,500 charts in the offices of 166 pediatricians and family physicians. Criteria for child health supervision and three diseases had been previously validated for relevance to health outcome and suitability for peer review. Overall documentation of criteria was approximately 50 per cent. Measurements and laboratory data were recorded frequently; counseling items infrequently. Pediatricians documented health supervision items more often than family physicians. Members of large groups recorded more than those in solo practice or small groups. The presence of equipment considered important for health care did not correlate with percentage of recording. The method of review was judged accurate and acceptable by physicians, but only 50 per cent said the results accurately portrayed their performance. Lack of accurate recording may make it impossible to achieve valid peer review of ambulatory child care.", "contents": "Office records in the evaluation of quality of care. Trained reviewers audited 10,500 charts in the offices of 166 pediatricians and family physicians. Criteria for child health supervision and three diseases had been previously validated for relevance to health outcome and suitability for peer review. Overall documentation of criteria was approximately 50 per cent. Measurements and laboratory data were recorded frequently; counseling items infrequently. Pediatricians documented health supervision items more often than family physicians. Members of large groups recorded more than those in solo practice or small groups. The presence of equipment considered important for health care did not correlate with percentage of recording. The method of review was judged accurate and acceptable by physicians, but only 50 per cent said the results accurately portrayed their performance. Lack of accurate recording may make it impossible to achieve valid peer review of ambulatory child care."} {"id": "PMID:1263627", "title": "Obstetric care in a family health-oriented university associated neighborhood health center.", "content": "The structure, staffing, and planning methods of the obstetric component of a family-oriented University Hospital associated family health care facility are briefly described. The interviews and screening procedures are outlined necessary to develop a broad data base for total health care planning. The roles of the members of the multiprofessional team employed are described with particular emphasis on the use of a nurse midwife as the primary obstetric care professional. Management procedures are referred to as well as the educational component present within such a program. The program is evaluated in terms of clinical outcome, patient and professional acceptance, and cost.", "contents": "Obstetric care in a family health-oriented university associated neighborhood health center. The structure, staffing, and planning methods of the obstetric component of a family-oriented University Hospital associated family health care facility are briefly described. The interviews and screening procedures are outlined necessary to develop a broad data base for total health care planning. The roles of the members of the multiprofessional team employed are described with particular emphasis on the use of a nurse midwife as the primary obstetric care professional. Management procedures are referred to as well as the educational component present within such a program. The program is evaluated in terms of clinical outcome, patient and professional acceptance, and cost."} {"id": "PMID:1263628", "title": "Patient acceptance of the family nurse practitioner.", "content": "Because of the limitations of published studies concerning patient acceptance of new health professionals and in the absence of published studies of patient acceptance of the family nurse practitioner, the present study compared levels of satisfaction among patients seeing a family nurse practitioner (Primex) with satisfaction levels among patients seeing traditional providers (doctors, nurses) withing the same setting. Based upon 1,912 patient-provider encounters using multiple evaluation criteria in ten ambulatory care settings, it was found that patient satisfaction with the Primex was equal to or more favorable than levels of satisfaction with traditional providers on four out of five measures.", "contents": "Patient acceptance of the family nurse practitioner. Because of the limitations of published studies concerning patient acceptance of new health professionals and in the absence of published studies of patient acceptance of the family nurse practitioner, the present study compared levels of satisfaction among patients seeing a family nurse practitioner (Primex) with satisfaction levels among patients seeing traditional providers (doctors, nurses) withing the same setting. Based upon 1,912 patient-provider encounters using multiple evaluation criteria in ten ambulatory care settings, it was found that patient satisfaction with the Primex was equal to or more favorable than levels of satisfaction with traditional providers on four out of five measures."} {"id": "PMID:1263629", "title": "Who is a nurse practitioner? Processes of care and patients' and physicians' perceptions.", "content": "During a repeat of a previous study of nurse practitioners conducted at the University of Kansas, an opportunity occurred to examine the impact of two different styles of care provided by nurse practitioners on patients and physicians with whom they worked. The two nurse practitioners involved had similar backgrounds in terms of work experience. The participated in the same training program for nurse practitioners, practice in the same environment, and cared for patients randomly allocated to one or the other practitioner. One practitioner saw her patients more often and for longer periods of time, ordered more medications, and less often sought physician consultation. She also was most optimistic regarding the impact of her services on patients' conditions. The other was more dependent upon physicians for validation of her actions. Physicians did not distinguish between the two practitioners in terms of their performance. However, patients cared for by the practitioner whose behavior suggested an integration of medical and nursing care processes saw nurses as a more common source of information about illness and demonstrated more significant shifts in preferences for services provided by nurses rather than physicians. No significant changes were noted from pretest values among patients cared for by the other nurse practitioner.", "contents": "Who is a nurse practitioner? Processes of care and patients' and physicians' perceptions. During a repeat of a previous study of nurse practitioners conducted at the University of Kansas, an opportunity occurred to examine the impact of two different styles of care provided by nurse practitioners on patients and physicians with whom they worked. The two nurse practitioners involved had similar backgrounds in terms of work experience. The participated in the same training program for nurse practitioners, practice in the same environment, and cared for patients randomly allocated to one or the other practitioner. One practitioner saw her patients more often and for longer periods of time, ordered more medications, and less often sought physician consultation. She also was most optimistic regarding the impact of her services on patients' conditions. The other was more dependent upon physicians for validation of her actions. Physicians did not distinguish between the two practitioners in terms of their performance. However, patients cared for by the practitioner whose behavior suggested an integration of medical and nursing care processes saw nurses as a more common source of information about illness and demonstrated more significant shifts in preferences for services provided by nurses rather than physicians. No significant changes were noted from pretest values among patients cared for by the other nurse practitioner."} {"id": "PMID:1263718", "title": "Pre and post-glycerol special audiometric tests battery results in endolymphatic hydrops.", "content": "The glycerol test for endolymphatic hydrops was administered to 17 patients exhibiting classical symptoms of Meniere's disease. A complete battery of audiometric tests including the SISI, TTD (Rosenberg variation). ABLB, Sweep Frequency Bekesy, two tests of speech discrimination (Rush Hughes and Northwestern), and air and bone conduction thresholds were administered pre and post-glycerol ingestion in order to determine the effect of osmotic diuresis. Improvement in pure-tone sensitivity and speech discrimination scores were most often observed. Among the special audiometric tests only the SISI scores exhibited changes, however, these could be related to the threshold changes. There were no significant differences observed in the threshold tone decay tests nor in the ABLB. The sweep frequency Bekesy test revealed only the changes which were observed in pure-tone sensitivity.", "contents": "Pre and post-glycerol special audiometric tests battery results in endolymphatic hydrops. The glycerol test for endolymphatic hydrops was administered to 17 patients exhibiting classical symptoms of Meniere's disease. A complete battery of audiometric tests including the SISI, TTD (Rosenberg variation). ABLB, Sweep Frequency Bekesy, two tests of speech discrimination (Rush Hughes and Northwestern), and air and bone conduction thresholds were administered pre and post-glycerol ingestion in order to determine the effect of osmotic diuresis. Improvement in pure-tone sensitivity and speech discrimination scores were most often observed. Among the special audiometric tests only the SISI scores exhibited changes, however, these could be related to the threshold changes. There were no significant differences observed in the threshold tone decay tests nor in the ABLB. The sweep frequency Bekesy test revealed only the changes which were observed in pure-tone sensitivity."} {"id": "PMID:1263719", "title": "Functional hearing loss.", "content": "Functional hearing loss is a rather common entity, although it probably is overlooked more often than not. In most instances, the services of an experienced audiologist are necessary if one is to detect these cases. First, one must consider carefully the patient's behavior before and during the otologic and audiologic examination, and note the referral source, if any, since patients with certain backgrounds are more apt to exhibit functional hearing loss than others. Second, careful attention is given to certain aspects of the initial basic audiometric examination. Discrepancies here often stand out and point clearly toward functional loss. A so-called \"modified approach\" to conventional audiometry has enabled us to detect almost all cases of functional hearing loss without resort to the special audiometric tests designed for that purpose.", "contents": "Functional hearing loss. Functional hearing loss is a rather common entity, although it probably is overlooked more often than not. In most instances, the services of an experienced audiologist are necessary if one is to detect these cases. First, one must consider carefully the patient's behavior before and during the otologic and audiologic examination, and note the referral source, if any, since patients with certain backgrounds are more apt to exhibit functional hearing loss than others. Second, careful attention is given to certain aspects of the initial basic audiometric examination. Discrepancies here often stand out and point clearly toward functional loss. A so-called \"modified approach\" to conventional audiometry has enabled us to detect almost all cases of functional hearing loss without resort to the special audiometric tests designed for that purpose."} {"id": "PMID:1263720", "title": "The management of sickle cell patients undergoing surgery.", "content": "Between 10 and 15 percent of blacks have sickle cell disease or sickle cell trait. Either is capable of a sickle cell crisis which could occur during a surgical procedure. Because of this, we as otolaryngologists should be aware of how to diagnose sickle cell disease and what specific measures should be followed in order to avoid a sickle cell crisis. This paper deals with specific diagnostic tests available, their interpretation, and our protocol for managment of these patients when they are in the hospital for a surgical procedure.", "contents": "The management of sickle cell patients undergoing surgery. Between 10 and 15 percent of blacks have sickle cell disease or sickle cell trait. Either is capable of a sickle cell crisis which could occur during a surgical procedure. Because of this, we as otolaryngologists should be aware of how to diagnose sickle cell disease and what specific measures should be followed in order to avoid a sickle cell crisis. This paper deals with specific diagnostic tests available, their interpretation, and our protocol for managment of these patients when they are in the hospital for a surgical procedure."} {"id": "PMID:1263721", "title": "Facial rehabilitation: surgical reconstruction following temporal bone resection.", "content": "Facial reconstruction and cosmetic surgery following extensive bone and soft tissue resection for carcinoma of the ear has not been emphasized in the past. Poor long term survival and local recurrence rates previously recluded considering extensive rehabilitative effort. A patient is presented, illustrating the problems resulting from major ablative surgery of the temporal bone. The surgical concepts and techniques used in this patient's facial rehabilitation are enumerated and described from both the functional of the principles used to other aspects of facial reconstruction are mentioned.", "contents": "Facial rehabilitation: surgical reconstruction following temporal bone resection. Facial reconstruction and cosmetic surgery following extensive bone and soft tissue resection for carcinoma of the ear has not been emphasized in the past. Poor long term survival and local recurrence rates previously recluded considering extensive rehabilitative effort. A patient is presented, illustrating the problems resulting from major ablative surgery of the temporal bone. The surgical concepts and techniques used in this patient's facial rehabilitation are enumerated and described from both the functional of the principles used to other aspects of facial reconstruction are mentioned."} {"id": "PMID:1263722", "title": "Thin rubber sheeting in frontal sinus surgery: animal and clinical studies.", "content": "Closure of the nasofrontal communication is the most common cause of failure of nonobliterative external of nonobliterative external frontal sinus operations for chronic sinus disease. To determine whether silicone rubber sheeting or tubing might prevent closure, we designed animal experiments and conducted a clinical study. We enlarged the nasofrontal duct in dogs, inserted silicone rubber tubing or sheeting and assessed ductal patency grossly and microscopically. The tubes prevented epithelization and failed to prevent local osteoblastic reaction, fibroplasia, and scar formation. In contrast, sheeting permitted rapid mucosal regeneration, less osteoblastic activity, and less fibrosis. Our 16 patients with chronic sinus disease underwent a modified Lynch operation, with enlargement of the nasofrontal duct and stenting with rubber tubes or sheeting. The sheeting provided the best long-term result. In our experience, it raised the success rate of the classic Lynch external operation.", "contents": "Thin rubber sheeting in frontal sinus surgery: animal and clinical studies. Closure of the nasofrontal communication is the most common cause of failure of nonobliterative external of nonobliterative external frontal sinus operations for chronic sinus disease. To determine whether silicone rubber sheeting or tubing might prevent closure, we designed animal experiments and conducted a clinical study. We enlarged the nasofrontal duct in dogs, inserted silicone rubber tubing or sheeting and assessed ductal patency grossly and microscopically. The tubes prevented epithelization and failed to prevent local osteoblastic reaction, fibroplasia, and scar formation. In contrast, sheeting permitted rapid mucosal regeneration, less osteoblastic activity, and less fibrosis. Our 16 patients with chronic sinus disease underwent a modified Lynch operation, with enlargement of the nasofrontal duct and stenting with rubber tubes or sheeting. The sheeting provided the best long-term result. In our experience, it raised the success rate of the classic Lynch external operation."} {"id": "PMID:1263723", "title": "The osteo-mucoperiosteal flap in repair of cerebrospinal fluid rhinorrhea.", "content": "Repair of fistulas producing cerebrospinal fluid rhinorrhea, as with any reconstructive operations, should take into account the basic principles of reconstructive surgery for best results: 1. tissue needing replacement should be replaced by like tissue; and 2. a flap is always superior to a graft. In the case of this disease, the tissue sealing the fistula should be a flap containing not only mucosa or mucoperiosteum, but also pedicled bone. Two kinds of regional flaps are described which successfully closed the fistula in each of three patients. Follow-up is long term.", "contents": "The osteo-mucoperiosteal flap in repair of cerebrospinal fluid rhinorrhea. Repair of fistulas producing cerebrospinal fluid rhinorrhea, as with any reconstructive operations, should take into account the basic principles of reconstructive surgery for best results: 1. tissue needing replacement should be replaced by like tissue; and 2. a flap is always superior to a graft. In the case of this disease, the tissue sealing the fistula should be a flap containing not only mucosa or mucoperiosteum, but also pedicled bone. Two kinds of regional flaps are described which successfully closed the fistula in each of three patients. Follow-up is long term."} {"id": "PMID:1263724", "title": "Nasal obstruction after rhinoplasty: etiology, and techniques for correction.", "content": "Of 1,000 consecutive patients who underwent rhinoplasty, about 10 percent had some nasal obstruction postoperatively. The majority of patients in whom the author performed the primary rhinoplasty had an obstructive, vasomotor type of rhinitis that ensued, and which usually could be cured by the injection of corticosteroids into the turbinates. Fifty patients had undergone rhinoplasty by other surgeons, and most of those patients requested surgical correction to relieve the nasal appearance. In those patients the causes of nasal obstruction were; pre-existent, undetected, or diagnosed but uncorrected, septal deviation; or turbinate hypertrophy; intranasal adhesions; scar tissue web formation in the nasal vault; inadequate nasal tip support, and alar collapse. The author's technique of surgical repair for each of these conditions is outlined.", "contents": "Nasal obstruction after rhinoplasty: etiology, and techniques for correction. Of 1,000 consecutive patients who underwent rhinoplasty, about 10 percent had some nasal obstruction postoperatively. The majority of patients in whom the author performed the primary rhinoplasty had an obstructive, vasomotor type of rhinitis that ensued, and which usually could be cured by the injection of corticosteroids into the turbinates. Fifty patients had undergone rhinoplasty by other surgeons, and most of those patients requested surgical correction to relieve the nasal appearance. In those patients the causes of nasal obstruction were; pre-existent, undetected, or diagnosed but uncorrected, septal deviation; or turbinate hypertrophy; intranasal adhesions; scar tissue web formation in the nasal vault; inadequate nasal tip support, and alar collapse. The author's technique of surgical repair for each of these conditions is outlined."} {"id": "PMID:1263725", "title": "Tuberculosis of the larynx.", "content": "Tuberculosis of the larynx, once a common disease, has become quite rare with the advent of anti-tuberculous chemotherapy. In the pre-antibiotic era two modes of laryngeal infection were recognized; bronchogenic and hematogenous. The literature is briefly reviewed. Thirteen patients in the past 15 years in whom tuberculous laryngitis was diagnosed upon indirect laryngoscopy by members of the University of Michigan Department of Otorhinolaryngology are presented. Bronchogenic infection was present in 11, and in two patients the disease was consistent with hematogenous spread. Tissue biopsy from a case of bronchogenic contamination demonstrated epithelioid tubercles, while numerous subepithelial acid-fast bacilli without typical tuberculous histological change were present in a case of hematogenous laryngeal infection. A case of cicatricial laryngeal stenosis was successfully treated surgically by laryngofissure, excision of fibrosis with arytenoidectomy, and free mucous membrane grafting. Finally, the initial subtle presentation of many of our patients emphasizes the importance of a consideration of tuberculosis in the differential diagnosis of chronic laryngitis.", "contents": "Tuberculosis of the larynx. Tuberculosis of the larynx, once a common disease, has become quite rare with the advent of anti-tuberculous chemotherapy. In the pre-antibiotic era two modes of laryngeal infection were recognized; bronchogenic and hematogenous. The literature is briefly reviewed. Thirteen patients in the past 15 years in whom tuberculous laryngitis was diagnosed upon indirect laryngoscopy by members of the University of Michigan Department of Otorhinolaryngology are presented. Bronchogenic infection was present in 11, and in two patients the disease was consistent with hematogenous spread. Tissue biopsy from a case of bronchogenic contamination demonstrated epithelioid tubercles, while numerous subepithelial acid-fast bacilli without typical tuberculous histological change were present in a case of hematogenous laryngeal infection. A case of cicatricial laryngeal stenosis was successfully treated surgically by laryngofissure, excision of fibrosis with arytenoidectomy, and free mucous membrane grafting. Finally, the initial subtle presentation of many of our patients emphasizes the importance of a consideration of tuberculosis in the differential diagnosis of chronic laryngitis."} {"id": "PMID:1263726", "title": "Difficult direct laryngoscopy.", "content": "This article reviews some of the problems involved in direct laryngoscopy. It suggests adequate preparation and evaluation of the patient to avoid complications. An evaluation of laryngospasm is given. Solutions of the problems are suggested using gear power assistance and adequate drugs for relaxation. The importance of correct positioning of the patient is emphasized and illustrated. This summarizes clinical judgment and successful evaluation of the difficult mechanical problems in the exposure of the vocal cords.", "contents": "Difficult direct laryngoscopy. This article reviews some of the problems involved in direct laryngoscopy. It suggests adequate preparation and evaluation of the patient to avoid complications. An evaluation of laryngospasm is given. Solutions of the problems are suggested using gear power assistance and adequate drugs for relaxation. The importance of correct positioning of the patient is emphasized and illustrated. This summarizes clinical judgment and successful evaluation of the difficult mechanical problems in the exposure of the vocal cords."} {"id": "PMID:1263727", "title": "Congenital subglottic fibroma in the newborn.", "content": "Congenital subglottic fibroma is a rare clinical entity. A review of references did not disclose any previous report. A case of congenital subglottic fibroma is presented. Embryology, etiology, symptomatology and pathology of congenital anomalies of the larynx are reviewed and management discussed.", "contents": "Congenital subglottic fibroma in the newborn. Congenital subglottic fibroma is a rare clinical entity. A review of references did not disclose any previous report. A case of congenital subglottic fibroma is presented. Embryology, etiology, symptomatology and pathology of congenital anomalies of the larynx are reviewed and management discussed."} {"id": "PMID:1263728", "title": "Glossopharyngeal neuralgia: surgical treatment and electron microscopic findings.", "content": "Seven cases of idiopathic glossopharyngeal neuralgia were treated with surgical resection via pharyngeal approach. Two of these cases showed a recurrence of neuralgia and subsequently, one of the recurring cases underwent a IXth nerve section through a cervical approach. The resected nerves were examined with the light and electron microscope. In five of seven cases, degeneration of myelinated fibers was observed. Under electron microscope, disarrangement and disorganization of the myelin sheath were found, while axonal degeneration was relatively rare. The author recommends an initial resection by the pharyngeal approach. In cases of recurrence, a subsequent attempt to resect the nerve should be made by the cervical approach.", "contents": "Glossopharyngeal neuralgia: surgical treatment and electron microscopic findings. Seven cases of idiopathic glossopharyngeal neuralgia were treated with surgical resection via pharyngeal approach. Two of these cases showed a recurrence of neuralgia and subsequently, one of the recurring cases underwent a IXth nerve section through a cervical approach. The resected nerves were examined with the light and electron microscope. In five of seven cases, degeneration of myelinated fibers was observed. Under electron microscope, disarrangement and disorganization of the myelin sheath were found, while axonal degeneration was relatively rare. The author recommends an initial resection by the pharyngeal approach. In cases of recurrence, a subsequent attempt to resect the nerve should be made by the cervical approach."} {"id": "PMID:1263729", "title": "Schwannoma presenting as a nasal polyp.", "content": "An unusual presentation and treatment of an intranasal Schwannoma are discussed. The clinical and pathological features are also reviewed.", "contents": "Schwannoma presenting as a nasal polyp. An unusual presentation and treatment of an intranasal Schwannoma are discussed. The clinical and pathological features are also reviewed."} {"id": "PMID:1263730", "title": "Sensori-neural hearing loss following radiotherapy to the nasopharynx.", "content": "A retrospective study was done to ascertain the risks of cochlear damage from radiotherapy of the nasopharynx. Audiometric evaluation, pre and post-radiotherapy, revealed that 7 out 13 patients had sustained sensori-neural deafness. Contrary to what is generally believed of the resistance of the cochlea to radiotherapeutic damage, eventual loss of hearing can occasionally be expected in patients undergoing radiation therapy for head and neck tumors.", "contents": "Sensori-neural hearing loss following radiotherapy to the nasopharynx. A retrospective study was done to ascertain the risks of cochlear damage from radiotherapy of the nasopharynx. Audiometric evaluation, pre and post-radiotherapy, revealed that 7 out 13 patients had sustained sensori-neural deafness. Contrary to what is generally believed of the resistance of the cochlea to radiotherapeutic damage, eventual loss of hearing can occasionally be expected in patients undergoing radiation therapy for head and neck tumors."} {"id": "PMID:1263757", "title": "Inhibition of cholesterol absorption by (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide in rats.", "content": "The effect of (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide (PTLA) on intestinal absorption of cholesterol was studied in rats. Oral administration of 15 mg PTLA to rats resulted in a significant (P less than 0.05) decrease in the radioactivity in serum and liver 4 hr after administration of labeled cholesterol. The effect of PTLA was greater on the absorption of cholesteryl oleate as compared with free cholesterol. The rate of hydrolysis of cholesteryl oleate in mucosal homogenates of rat intestine was decreased with PTLA, suggesting that the inhibition of cholesterol absorption by PTLA is related to its effect on cholesteryl ester hydrolysis in the intestine.", "contents": "Inhibition of cholesterol absorption by (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide in rats. The effect of (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide (PTLA) on intestinal absorption of cholesterol was studied in rats. Oral administration of 15 mg PTLA to rats resulted in a significant (P less than 0.05) decrease in the radioactivity in serum and liver 4 hr after administration of labeled cholesterol. The effect of PTLA was greater on the absorption of cholesteryl oleate as compared with free cholesterol. The rate of hydrolysis of cholesteryl oleate in mucosal homogenates of rat intestine was decreased with PTLA, suggesting that the inhibition of cholesterol absorption by PTLA is related to its effect on cholesteryl ester hydrolysis in the intestine."} {"id": "PMID:1263758", "title": "Effect of (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide on lipid levels in serum and liver in cholesterol-fed rats.", "content": "The effect of (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide (PTLA) on lipid levels in serum and liver was compared with that of sitosterols in rats maintained on a diet supplemented with 1% of cholesterol, 0.5% of ox bile extracts, and 10% of hydrogenated coconut oil for 8 weeks. When PTLA was added to the diet at a level of 0.1%, the mean liver cholesterol level of male rats was reduced to 41% of the control and that of female rats was reduced to 19% of the control. In female rats, which showed higher cholesterol levels in serum and liver than male rats after cholesterol feeding, PTLA lowered the liver cholesterol level even at 0.0008% in the diet. Serum cholesterol was lowered by PTLA but not so markedly as liver cholesterol. The inhibition of cholesterol deposition in the liver suggests that the interference with cholesterol absorption is one of the main actions of PTLA. Sitosterols showed a similar pattern of lipid-lowering action, but the potency was far less than that of PTLA.", "contents": "Effect of (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide on lipid levels in serum and liver in cholesterol-fed rats. The effect of (-)N-[alpha-phenyl-beta-(p-tolyl)ethyl] linoleamide (PTLA) on lipid levels in serum and liver was compared with that of sitosterols in rats maintained on a diet supplemented with 1% of cholesterol, 0.5% of ox bile extracts, and 10% of hydrogenated coconut oil for 8 weeks. When PTLA was added to the diet at a level of 0.1%, the mean liver cholesterol level of male rats was reduced to 41% of the control and that of female rats was reduced to 19% of the control. In female rats, which showed higher cholesterol levels in serum and liver than male rats after cholesterol feeding, PTLA lowered the liver cholesterol level even at 0.0008% in the diet. Serum cholesterol was lowered by PTLA but not so markedly as liver cholesterol. The inhibition of cholesterol deposition in the liver suggests that the interference with cholesterol absorption is one of the main actions of PTLA. Sitosterols showed a similar pattern of lipid-lowering action, but the potency was far less than that of PTLA."} {"id": "PMID:1263759", "title": "Effects of pentadecan-2-one on the growth of cells in culture.", "content": "The effect of inclusion of trace amounts of pentadecan-2-one in the incubation medium on the growth of HeLa Cells was evaluated by measuring viable cell counts (cells excluding trypan blue) and incorporation of [14C] leucine into acid precipitable protein. Evidence is presented to show that exposure of the cells to trace amounts of the methyl ketone, 36mug/ml, effectively inhibits cell growth. This inhibition is relieved by simultaneously incubating the cells with a long chain primary alcohol, hexadecan-1- o1, but not with the secondary alcohol, pentadecan-2-o1. The observation that the ethyl ketone, hexadecan-3-one, also inhibits cell growth but at higher concentrations than that observed with pentadecan-2-one and that pentadecan-2-o1 at similar concentrations has no effect on cell growth indicates that, for optimal effect, the keto function must be at the 2-position. Inhibition of cell growth by pentadecan-2-one is not unique to HeLa cells, as suggested by the inhibitory effects of this lipid type on the growth of other malignant cell lines of human origin.", "contents": "Effects of pentadecan-2-one on the growth of cells in culture. The effect of inclusion of trace amounts of pentadecan-2-one in the incubation medium on the growth of HeLa Cells was evaluated by measuring viable cell counts (cells excluding trypan blue) and incorporation of [14C] leucine into acid precipitable protein. Evidence is presented to show that exposure of the cells to trace amounts of the methyl ketone, 36mug/ml, effectively inhibits cell growth. This inhibition is relieved by simultaneously incubating the cells with a long chain primary alcohol, hexadecan-1- o1, but not with the secondary alcohol, pentadecan-2-o1. The observation that the ethyl ketone, hexadecan-3-one, also inhibits cell growth but at higher concentrations than that observed with pentadecan-2-one and that pentadecan-2-o1 at similar concentrations has no effect on cell growth indicates that, for optimal effect, the keto function must be at the 2-position. Inhibition of cell growth by pentadecan-2-one is not unique to HeLa cells, as suggested by the inhibitory effects of this lipid type on the growth of other malignant cell lines of human origin."} {"id": "PMID:1263760", "title": "Rat testicular lipids and dietary isomeric fatty acids in essential fatty acid deficiency.", "content": "Weanling rats were fed essential fatty acid-deficient diets, either completely fat-free, or with partially hydrogenated fish oil (PHFO, 28 wt %), or with fractions derived from PHFO containing primarily positional isomers of trans-eicosenoate (20:1, 3 wt %) or trans-docosenoate (22:1, 3 wt %). Control animals were fed a peanut oil-containing diet (28 wt %). After 5 or 15 weeks on the diet, the content of neutral and phosphorus-containing lipids in the testes was determined. The fatty acid distribution in major lipid classes was analyzed for animals fed the diets for 15 weeks. The testicular stage of maturation or degeneration was assessed by histology. The group fed PHFO exhibited signs of complete testicular degeneration, or lack of maturation, already after 5 weeks, whereas the animals on the diets with the very long chain monoenoic acids suffered severe degenerations only after 15 weeks. In the PHFO-fed rats, a sharp decline in the concentration of testicular triacylglycerols was observed. In all of the essential fatty acid-deficient groups, an increase in testicular sphingomyelin was observed. Cholesterol levels were fairly similar among all dietary groups. The total testicular fatty acids of the PHFO-fed animals contained somewhat more eicosadienoic acid than found in the other groups, and somewhat less (n-9)-acids. In all EFA-deficient groups, (n-6)-acids were lowered, in particular in triacylglycerols and phosphatidyl cholines. The PHFO group did not show a lower (n-6)-concentration than the other deficient groups, in spite of the more severe symptoms of deficiency. There was no evidence of a major accumulation of long chain isomeric fatty acids in the degenerated testes of the PHFO-, 20:1-, and 22:1-fed groups.", "contents": "Rat testicular lipids and dietary isomeric fatty acids in essential fatty acid deficiency. Weanling rats were fed essential fatty acid-deficient diets, either completely fat-free, or with partially hydrogenated fish oil (PHFO, 28 wt %), or with fractions derived from PHFO containing primarily positional isomers of trans-eicosenoate (20:1, 3 wt %) or trans-docosenoate (22:1, 3 wt %). Control animals were fed a peanut oil-containing diet (28 wt %). After 5 or 15 weeks on the diet, the content of neutral and phosphorus-containing lipids in the testes was determined. The fatty acid distribution in major lipid classes was analyzed for animals fed the diets for 15 weeks. The testicular stage of maturation or degeneration was assessed by histology. The group fed PHFO exhibited signs of complete testicular degeneration, or lack of maturation, already after 5 weeks, whereas the animals on the diets with the very long chain monoenoic acids suffered severe degenerations only after 15 weeks. In the PHFO-fed rats, a sharp decline in the concentration of testicular triacylglycerols was observed. In all of the essential fatty acid-deficient groups, an increase in testicular sphingomyelin was observed. Cholesterol levels were fairly similar among all dietary groups. The total testicular fatty acids of the PHFO-fed animals contained somewhat more eicosadienoic acid than found in the other groups, and somewhat less (n-9)-acids. In all EFA-deficient groups, (n-6)-acids were lowered, in particular in triacylglycerols and phosphatidyl cholines. The PHFO group did not show a lower (n-6)-concentration than the other deficient groups, in spite of the more severe symptoms of deficiency. There was no evidence of a major accumulation of long chain isomeric fatty acids in the degenerated testes of the PHFO-, 20:1-, and 22:1-fed groups."} {"id": "PMID:1263761", "title": "Positional analysis of isovaleroyl triglycerides using proton magnetic resonance with Eu(fod)3 and Pr(fod)3 shift reagents: II. Cetacean triglycerides.", "content": "The positional distribution of isovaleric acid in natural cetacean triglycerides has been studied using proton magnetic resonance with lanthanide shift reagents. Twenty-nine samples of melon, jaw, and blubber triglycerides from 13 genera in the Delphinidae, Phocoenidae, and Monodontidae families were examined. Isovaleric acid was found esterified only at the 1,3-positions in the monoisovaleroyl and diisovaleroyl triglycerides of these animals.", "contents": "Positional analysis of isovaleroyl triglycerides using proton magnetic resonance with Eu(fod)3 and Pr(fod)3 shift reagents: II. Cetacean triglycerides. The positional distribution of isovaleric acid in natural cetacean triglycerides has been studied using proton magnetic resonance with lanthanide shift reagents. Twenty-nine samples of melon, jaw, and blubber triglycerides from 13 genera in the Delphinidae, Phocoenidae, and Monodontidae families were examined. Isovaleric acid was found esterified only at the 1,3-positions in the monoisovaleroyl and diisovaleroyl triglycerides of these animals."} {"id": "PMID:1263762", "title": "Influence of diet on conversion of 14C1-linolenic acid to docosahexaenoic acid in the rat.", "content": "14C1-Linolenic acid was incorporated into lipids of hearts, livers, and carcasses of male rats. We studied the influence of diet composition on extent and distribution of radioactivity. A CHOW diet, a purified, essential fatty acid (EFA)-deficient diet, a purified control diet, and EFA-deficient diets with four fatty acid supplements were used. Supplements of 18:2n-6, 20:4n-6, 15:3n-3, and 22:6n-3 were given as single doses. Radioactivities in liver phosphatidyl ethanolamines (PE), phosphatidyl cholines, and neutral lipids were measured. The distribution of radioactivity among the fatty acids in liver phospholipids was determined. Rats on CHOW diet incorporated far less radioactivity than any other group into lipids of hearts and livers. Most of the activity in livers was recovered as 20:5n-3 and 22:6n-3 in all rats. In EFA-deficient rats, the radioactivity in 22:6n-3 of liver PE was still increasing 36 hr after 14C1-linolenic acid had been administered. The n-6 supplements (18:2n-6 and 20:4n-6) seemed to reduce the coversion of 20:4n-3 to 20:5n-3 (desaturation), whereas the n-3 supplements (18:3n-3 and 22:6n-3) reduced the conversion of 20:5n-3 to 22:5n-3 (elongation). Formation of 22:6n-3 may be controlled by 22:6n-3 itself at the elongation of 20:5n-3 to 22:5n-3.", "contents": "Influence of diet on conversion of 14C1-linolenic acid to docosahexaenoic acid in the rat. 14C1-Linolenic acid was incorporated into lipids of hearts, livers, and carcasses of male rats. We studied the influence of diet composition on extent and distribution of radioactivity. A CHOW diet, a purified, essential fatty acid (EFA)-deficient diet, a purified control diet, and EFA-deficient diets with four fatty acid supplements were used. Supplements of 18:2n-6, 20:4n-6, 15:3n-3, and 22:6n-3 were given as single doses. Radioactivities in liver phosphatidyl ethanolamines (PE), phosphatidyl cholines, and neutral lipids were measured. The distribution of radioactivity among the fatty acids in liver phospholipids was determined. Rats on CHOW diet incorporated far less radioactivity than any other group into lipids of hearts and livers. Most of the activity in livers was recovered as 20:5n-3 and 22:6n-3 in all rats. In EFA-deficient rats, the radioactivity in 22:6n-3 of liver PE was still increasing 36 hr after 14C1-linolenic acid had been administered. The n-6 supplements (18:2n-6 and 20:4n-6) seemed to reduce the coversion of 20:4n-3 to 20:5n-3 (desaturation), whereas the n-3 supplements (18:3n-3 and 22:6n-3) reduced the conversion of 20:5n-3 to 22:5n-3 (elongation). Formation of 22:6n-3 may be controlled by 22:6n-3 itself at the elongation of 20:5n-3 to 22:5n-3."} {"id": "PMID:1263763", "title": "Physiological and analytical variation in cholesterol and triglycerides.", "content": "Plasma cholesterol and triglyceride levels were determined, on each of two AutoAnalyzer systems in 11 healthy subjects, weekly over a 10-week and monthly over a 12-month period. Analytical variation was 1-2% for cholesterol and 2-5% for triglyceride. Cholesterol and triglyceride values on frozen quality control serum pools were not indicative of absolute values on fresh plasma. Even though the two AutoAnalyzer systems averaged within 1-2 mg/dl for triglyceride and cholesterol on the serum quality control pools during the 12-month period, the two systems differed by 7-8 mg/dl on fresh or frozen plasma samples. The coefficient of physiological variation on the 10 weekly samples averaged 5% (range 3-10%) for plasma cholesterol and 18% (range 9-27%) for plasma triglyceride. Analysis of the monthly samples suggested significant (P less than 0.05) seasonal trends: cholesterol was highest in the winter months and lowest in October, whereas triglyceride was highest in January and February and lowest in May and December. We conclude that intra-individual variation can be an important source of error in attempting to make a genetic diagnosis of hyperlipidemia and/or in evaluating hypolipidemic regimens in a given subject.", "contents": "Physiological and analytical variation in cholesterol and triglycerides. Plasma cholesterol and triglyceride levels were determined, on each of two AutoAnalyzer systems in 11 healthy subjects, weekly over a 10-week and monthly over a 12-month period. Analytical variation was 1-2% for cholesterol and 2-5% for triglyceride. Cholesterol and triglyceride values on frozen quality control serum pools were not indicative of absolute values on fresh plasma. Even though the two AutoAnalyzer systems averaged within 1-2 mg/dl for triglyceride and cholesterol on the serum quality control pools during the 12-month period, the two systems differed by 7-8 mg/dl on fresh or frozen plasma samples. The coefficient of physiological variation on the 10 weekly samples averaged 5% (range 3-10%) for plasma cholesterol and 18% (range 9-27%) for plasma triglyceride. Analysis of the monthly samples suggested significant (P less than 0.05) seasonal trends: cholesterol was highest in the winter months and lowest in October, whereas triglyceride was highest in January and February and lowest in May and December. We conclude that intra-individual variation can be an important source of error in attempting to make a genetic diagnosis of hyperlipidemia and/or in evaluating hypolipidemic regimens in a given subject."} {"id": "PMID:1263764", "title": "Mass spectrometric analysis of the fatty acids and nonsaponifiable lipids of Eimeria tenella oocysts.", "content": "The fatty acids and nonsaponifiable lipids of Eimeria tenella oocysts were analyzed by gas liquid chromatography and combined gas liquid chromatography-mass spectrometry. The fatty acids detected were identified as C14:0, C16:0, C16:1, C18:0, C18:1, and C18:2. Though the wt of the fatty acid fraction decreased during sporulation from 91 mug per 10(6) oocysts to 47 mug per 10(6) oocysts, the relative amounts of these fatty acids did not change appreciably. The nonsaponifiable lipids of E. tenella consisted of cholesterol and unbranched primary alcohols of 22, 24, 26, 28, 30, and 32 carbons. Mass fragmentography demonstrated that each species of alcohol consisted of saturated and monounsaturated derivatives. Trimethylsilyl ethers of fatty alcohols were found to offer several important advantages over free alcohols for mass spectrometric characterization. Before sporulation, most fatty alcohols were in the oocyst wall. During sporulation, the wt of the nonsaponifiable lipids increased from 16 mug per 10(6) oocysts to 44 mug per 10(6) oocysts due largely to synthesis of C24 and C26 alcohols. The newly synthesized fatty alcohols were not deposited in the oocyst wall.", "contents": "Mass spectrometric analysis of the fatty acids and nonsaponifiable lipids of Eimeria tenella oocysts. The fatty acids and nonsaponifiable lipids of Eimeria tenella oocysts were analyzed by gas liquid chromatography and combined gas liquid chromatography-mass spectrometry. The fatty acids detected were identified as C14:0, C16:0, C16:1, C18:0, C18:1, and C18:2. Though the wt of the fatty acid fraction decreased during sporulation from 91 mug per 10(6) oocysts to 47 mug per 10(6) oocysts, the relative amounts of these fatty acids did not change appreciably. The nonsaponifiable lipids of E. tenella consisted of cholesterol and unbranched primary alcohols of 22, 24, 26, 28, 30, and 32 carbons. Mass fragmentography demonstrated that each species of alcohol consisted of saturated and monounsaturated derivatives. Trimethylsilyl ethers of fatty alcohols were found to offer several important advantages over free alcohols for mass spectrometric characterization. Before sporulation, most fatty alcohols were in the oocyst wall. During sporulation, the wt of the nonsaponifiable lipids increased from 16 mug per 10(6) oocysts to 44 mug per 10(6) oocysts due largely to synthesis of C24 and C26 alcohols. The newly synthesized fatty alcohols were not deposited in the oocyst wall."} {"id": "PMID:1263765", "title": "Effect of dietary di-2-ethylhexyl phthalate on lipid biosynthesis in selected tissues from the rat, in vitro.", "content": "Di-2-ethylhexyl phthalate (DEHP), a plasticizer commonly used in the production of polyvinyl chloride plastics, has become an environmental pollutant. At the present time, the biological significance of phthalates in the environment is unknown. In the present studies, we observed that addition of DEHP to a stock diet of rats resulted in marked effects on incorporation of 14C-acetate into lipid by liver and kidney slices; other organs, such as heart, testes, and aorta, were unaffected. Incorporation of 14C-acetate into total lipid of liver (dpm/mg wet wt) from rats fed 0.5% or 1.0% DEHP for 10 or 18 days, respectively, was decreased to ca. 50% of control values. The decreased incorporation into liver lipid is not attributable to any one lipid fraction, inasmuch as incorporation into the phospholipid, sterol + diglyceride, free fatty acid, triglyceride, and sterol ester + hydrocarbon fractions was decreased 30-70% with respect to controls. In addition, the percent distribution of 14C-acetate among the individual phospholipids was ca. 25% lower in phosphatidyl choline of the DEHP-fed rats. In rats fed 0.5% DEHP, incorporation of 14C-acetate into total lipid of kidney was similar to control values, but incorporation into the triglyceride and sterol ester + hydrocarbon fraction was decreased 30-40%, whereas incorporation into the sterol + diglyceride fraction was increased 38%. Livers from DEHP-fed rats were ca. 20% larger than livers from control rats and, at the 0.5% level of DEHP feeding, testes wts were elevated; no significant changes were noted in wts of spleen, heart, aorta, kidney, or body wt gains in rats fed DEHP. These studies emphasize a subtle toxicity of phthalate esters not previously reported and emphasize the need for further biochemical studies to evaluate the effect of phthalates on biological systems.", "contents": "Effect of dietary di-2-ethylhexyl phthalate on lipid biosynthesis in selected tissues from the rat, in vitro. Di-2-ethylhexyl phthalate (DEHP), a plasticizer commonly used in the production of polyvinyl chloride plastics, has become an environmental pollutant. At the present time, the biological significance of phthalates in the environment is unknown. In the present studies, we observed that addition of DEHP to a stock diet of rats resulted in marked effects on incorporation of 14C-acetate into lipid by liver and kidney slices; other organs, such as heart, testes, and aorta, were unaffected. Incorporation of 14C-acetate into total lipid of liver (dpm/mg wet wt) from rats fed 0.5% or 1.0% DEHP for 10 or 18 days, respectively, was decreased to ca. 50% of control values. The decreased incorporation into liver lipid is not attributable to any one lipid fraction, inasmuch as incorporation into the phospholipid, sterol + diglyceride, free fatty acid, triglyceride, and sterol ester + hydrocarbon fractions was decreased 30-70% with respect to controls. In addition, the percent distribution of 14C-acetate among the individual phospholipids was ca. 25% lower in phosphatidyl choline of the DEHP-fed rats. In rats fed 0.5% DEHP, incorporation of 14C-acetate into total lipid of kidney was similar to control values, but incorporation into the triglyceride and sterol ester + hydrocarbon fraction was decreased 30-40%, whereas incorporation into the sterol + diglyceride fraction was increased 38%. Livers from DEHP-fed rats were ca. 20% larger than livers from control rats and, at the 0.5% level of DEHP feeding, testes wts were elevated; no significant changes were noted in wts of spleen, heart, aorta, kidney, or body wt gains in rats fed DEHP. These studies emphasize a subtle toxicity of phthalate esters not previously reported and emphasize the need for further biochemical studies to evaluate the effect of phthalates on biological systems."} {"id": "PMID:1263766", "title": "beta-Oxidative cleavage of octanoyl- and dodecanoyl-CoA in rat liver cytoplasm.", "content": "[12-14C] Dodecanoyl-CoA and [8-14C] octanoyl-CoA were tested as substrates for shortening the chain by two carbon atoms using both the 105,000 x g soluble fraction and the sonicated mitochondrial fraction of rat liver homogenate as the enzyme source. Both substrates were metabolized by the cytoplasmic enzymes giving rise to the accumulation of intermediates of the beta-oxidation process without formation of two carbon units from the methyl carbon of the acyl residue. A new method is described which allows quantitative estimation of volatile fatty acids formed by beta-oxidation of dodecanoyl- and octanoyl- Coenzyme A.", "contents": "beta-Oxidative cleavage of octanoyl- and dodecanoyl-CoA in rat liver cytoplasm. [12-14C] Dodecanoyl-CoA and [8-14C] octanoyl-CoA were tested as substrates for shortening the chain by two carbon atoms using both the 105,000 x g soluble fraction and the sonicated mitochondrial fraction of rat liver homogenate as the enzyme source. Both substrates were metabolized by the cytoplasmic enzymes giving rise to the accumulation of intermediates of the beta-oxidation process without formation of two carbon units from the methyl carbon of the acyl residue. A new method is described which allows quantitative estimation of volatile fatty acids formed by beta-oxidation of dodecanoyl- and octanoyl- Coenzyme A."} {"id": "PMID:1263768", "title": "trans-6-Hexadecenoic acid in the spadefish Chaetodipterus faber.", "content": "Fatty acid methyl esters were prepared from spadefish (Chaetodipterus faber) liver oil and were analyzed by open tublar gas chromatography. The unusual fatty acid trans-6-hexadecenoic acid was identified as a major monoenoic component by reductive ozonolysis and by mass spectrometry of the di-trimethylsilyl ether. Very minor amounts of 7-methyl-7-hexadecenoic acid were found.", "contents": "trans-6-Hexadecenoic acid in the spadefish Chaetodipterus faber. Fatty acid methyl esters were prepared from spadefish (Chaetodipterus faber) liver oil and were analyzed by open tublar gas chromatography. The unusual fatty acid trans-6-hexadecenoic acid was identified as a major monoenoic component by reductive ozonolysis and by mass spectrometry of the di-trimethylsilyl ether. Very minor amounts of 7-methyl-7-hexadecenoic acid were found."} {"id": "PMID:1263767", "title": "Relationship between desaturation and chain elongation of palmityl-CoA in rat liver microsomes.", "content": "The relationship between desaturation and chain elongation of palmityl-CoA was studied in rat liver microsomes. Enzyme activities for desaturation and chain elongation were stimulated by re-feeding starved rats. The activities of desaturation and chain elongation in re-fed rats were four- and twofold greater than those in normal rats, respectively. When a sonicated dispersion of lecithin was added to the incubation medium containing both reactions, chain elongation activity, especially formation of stearic acid, was stimulated and desaturation activity was apparently depressed.", "contents": "Relationship between desaturation and chain elongation of palmityl-CoA in rat liver microsomes. The relationship between desaturation and chain elongation of palmityl-CoA was studied in rat liver microsomes. Enzyme activities for desaturation and chain elongation were stimulated by re-feeding starved rats. The activities of desaturation and chain elongation in re-fed rats were four- and twofold greater than those in normal rats, respectively. When a sonicated dispersion of lecithin was added to the incubation medium containing both reactions, chain elongation activity, especially formation of stearic acid, was stimulated and desaturation activity was apparently depressed."} {"id": "PMID:1263770", "title": "Biosynthesis of molecular species of CDP-diglyceride from endogenously-labeled phosphatidate in rat liver microsomes.", "content": "The biosynthesis of [14C] CDP-diglyceride was studied using rat liver microsomes which were endogenously labeled with [14C] phosphatidic acid by preincubation of unlabeled microsomes with sn-[14C] glycerol-3-phosphate and appropriate cofactors. The formation of CDP-diglyceride from radioactive phosphatidate showed an absolute requirement for CTP and MgCl2. The newly formed [14C] CDP-diglyceride was characterized by thin layer chromatography (TLC), isotopic labeling from radioactive CTP, and its ability to serve as substrate for the microsomal enzyme, CDP-diglyceride: inositol phosphatidyltransferase. The distributions of radioactive glycerol-3-phosphate among the various chemical classes of microsomal [14C] phosphatidate and [14C] CDP-diglyceride were determined following argentation TLC of their 1,2-diglyceride acetate derivatives. Most of the radioactivity among the phosphatidic acids was present in the monoenoic (36%) and dienoic (33%) molecular species, whereas 10, 8, 4, and 8% were associated with the saturates, trienes, tetraenes, and polyenes, respectively. Similar distributions of radioactivity were found among the corresponding classes of newly formed CDP-diglyceride. Only a slight enrichment of radioactivity in the tetraenoic CDP-diglyceride was found relative to the corresponding phosphatidates. Therefore, under the conditions of study, the microsomal CTP: phosphatidate cytidylyltransferase produces mainly monoenoic and dienoic species of CDP-diglyceride and shows little specificity towards different molecular species of phosphatidic acids. The present results suggest also that the arachidonoyl phosphatidate derived from the microsomal acylation of sn-glycerol-3-phosphate is not likely the major source of arachidonic acid in liver phosphatidylinositol.", "contents": "Biosynthesis of molecular species of CDP-diglyceride from endogenously-labeled phosphatidate in rat liver microsomes. The biosynthesis of [14C] CDP-diglyceride was studied using rat liver microsomes which were endogenously labeled with [14C] phosphatidic acid by preincubation of unlabeled microsomes with sn-[14C] glycerol-3-phosphate and appropriate cofactors. The formation of CDP-diglyceride from radioactive phosphatidate showed an absolute requirement for CTP and MgCl2. The newly formed [14C] CDP-diglyceride was characterized by thin layer chromatography (TLC), isotopic labeling from radioactive CTP, and its ability to serve as substrate for the microsomal enzyme, CDP-diglyceride: inositol phosphatidyltransferase. The distributions of radioactive glycerol-3-phosphate among the various chemical classes of microsomal [14C] phosphatidate and [14C] CDP-diglyceride were determined following argentation TLC of their 1,2-diglyceride acetate derivatives. Most of the radioactivity among the phosphatidic acids was present in the monoenoic (36%) and dienoic (33%) molecular species, whereas 10, 8, 4, and 8% were associated with the saturates, trienes, tetraenes, and polyenes, respectively. Similar distributions of radioactivity were found among the corresponding classes of newly formed CDP-diglyceride. Only a slight enrichment of radioactivity in the tetraenoic CDP-diglyceride was found relative to the corresponding phosphatidates. Therefore, under the conditions of study, the microsomal CTP: phosphatidate cytidylyltransferase produces mainly monoenoic and dienoic species of CDP-diglyceride and shows little specificity towards different molecular species of phosphatidic acids. The present results suggest also that the arachidonoyl phosphatidate derived from the microsomal acylation of sn-glycerol-3-phosphate is not likely the major source of arachidonic acid in liver phosphatidylinositol."} {"id": "PMID:1263771", "title": "Effects of dietary saturated and trans fatty acids on tissue lipid composition and serum LCAT activity in the rat.", "content": "Groups of rats were fed from weaning with diets containing 5% by wt of hydrogenated coconut oil (HCO), safflower oil, or a concentrate of ethyl elaidate and linolelaidate (TRANS) as the sole source of dietary fat. Fatty acid composition of the lipid classes from serum, liver, heart, and kidney was determined, and the serum lecithin: cholesterol acyl transferase (LCAT) activities were assayed for each animal. Serum LCAT activity was increased by both the HCO and TRANS diets in the early stages of the development of an essential fatty acid (EFA) deficiency but was suppressed in the animals of the TRANS group as they became older. The HCO and TRANS groups exhibited changes in tissue lipid fatty acid composition, as well as reduced growth, characteristic of an EFA deficiency. Coversion of oleic acid to eicosatrienoic acid was impaired in the animals fed the TRANS diet, greatly increasing the octadecenoic acid content of the tissue lipids at the expense of eicosatrienoic acid. The TRANS diet also suppressed incorporation of eicosatrienoic acid into cholesteryl esters of tissue and serum, indicating that, when fed as the sole source of unsaturated fat, trans fatty acids influenced the metabolism of unsaturated fatty acids and cholesterol.", "contents": "Effects of dietary saturated and trans fatty acids on tissue lipid composition and serum LCAT activity in the rat. Groups of rats were fed from weaning with diets containing 5% by wt of hydrogenated coconut oil (HCO), safflower oil, or a concentrate of ethyl elaidate and linolelaidate (TRANS) as the sole source of dietary fat. Fatty acid composition of the lipid classes from serum, liver, heart, and kidney was determined, and the serum lecithin: cholesterol acyl transferase (LCAT) activities were assayed for each animal. Serum LCAT activity was increased by both the HCO and TRANS diets in the early stages of the development of an essential fatty acid (EFA) deficiency but was suppressed in the animals of the TRANS group as they became older. The HCO and TRANS groups exhibited changes in tissue lipid fatty acid composition, as well as reduced growth, characteristic of an EFA deficiency. Coversion of oleic acid to eicosatrienoic acid was impaired in the animals fed the TRANS diet, greatly increasing the octadecenoic acid content of the tissue lipids at the expense of eicosatrienoic acid. The TRANS diet also suppressed incorporation of eicosatrienoic acid into cholesteryl esters of tissue and serum, indicating that, when fed as the sole source of unsaturated fat, trans fatty acids influenced the metabolism of unsaturated fatty acids and cholesterol."} {"id": "PMID:1263772", "title": "Myocardial lipids and nucleotides of rats fed olive oil or rapeseed oil.", "content": "After 1 week, the level of myocardial fatty acids was 4 times greater in young rats fed high erucic rapeseed oil than in those fed oliver oil. The proportion of erucic acid was 5.6% in the mitochondrial fraction, 15.1% in the microsomal fraction, and 34.8% in the floating fat fraction. This incorporation of erucic acid into triglycerides of the floating fat was evidence of esterification. The changes in the mitochondrial lipids did not alter the content of adenine nucleotides of the myocardium nor its apparent capacity to oxidize substrates.", "contents": "Myocardial lipids and nucleotides of rats fed olive oil or rapeseed oil. After 1 week, the level of myocardial fatty acids was 4 times greater in young rats fed high erucic rapeseed oil than in those fed oliver oil. The proportion of erucic acid was 5.6% in the mitochondrial fraction, 15.1% in the microsomal fraction, and 34.8% in the floating fat fraction. This incorporation of erucic acid into triglycerides of the floating fat was evidence of esterification. The changes in the mitochondrial lipids did not alter the content of adenine nucleotides of the myocardium nor its apparent capacity to oxidize substrates."} {"id": "PMID:1263773", "title": "Changes in muscle lipid composition and resistance adaptation to temperature in the freshwater crayfish, Austropotamobius pallipes.", "content": "The phospholipid and fatty acid composition of muscle lipid extracts from crayfish acclimated to 4 C and 25 C (18 hr-light photoperiod) were analyzed. The phospholipid content and class distribution, and cholesterol content were unaffected by the acclimation treatment. Unsaturation of muscle phosphoglycerides was higher in cold acclimated crayfish. Serine/inositol phosphoglycerides from cold-acclimated animals showed somewhat higher proportions of mono- and polyunsaturated fatty acids, whereas choline and ethanolamine phosphoglycerides were less affected. This was correlated with a decreased resistance of cold-acclimated crayfish to lethal high temperature. Acclimation at 4 C under an 8 hr-light photoperiod caused an increased fatty acid unsaturation of the total phospholipid fraction compared to the 4 C, 18 hr-light photoperiod acclimated animals. The resistance of 4 C acclimated crayfish to lethal high temperature, however, was unaffected by daylength treatment. The resistance of freshwater crayfish to lethal high temperature is not simply related to the degree of saturation of the muscle phospholipids. It is suggested that a breakdown in the integrity of a bulk-lipid bilayer is not involved in the process of heat death; rather, that a membrane-bound protein factor, whose thermal sensitivity is modified by changes in its phospholipid environment during temperature adaptation but not during photoperiod adaptation, is the primary site of heat injury.", "contents": "Changes in muscle lipid composition and resistance adaptation to temperature in the freshwater crayfish, Austropotamobius pallipes. The phospholipid and fatty acid composition of muscle lipid extracts from crayfish acclimated to 4 C and 25 C (18 hr-light photoperiod) were analyzed. The phospholipid content and class distribution, and cholesterol content were unaffected by the acclimation treatment. Unsaturation of muscle phosphoglycerides was higher in cold acclimated crayfish. Serine/inositol phosphoglycerides from cold-acclimated animals showed somewhat higher proportions of mono- and polyunsaturated fatty acids, whereas choline and ethanolamine phosphoglycerides were less affected. This was correlated with a decreased resistance of cold-acclimated crayfish to lethal high temperature. Acclimation at 4 C under an 8 hr-light photoperiod caused an increased fatty acid unsaturation of the total phospholipid fraction compared to the 4 C, 18 hr-light photoperiod acclimated animals. The resistance of 4 C acclimated crayfish to lethal high temperature, however, was unaffected by daylength treatment. The resistance of freshwater crayfish to lethal high temperature is not simply related to the degree of saturation of the muscle phospholipids. It is suggested that a breakdown in the integrity of a bulk-lipid bilayer is not involved in the process of heat death; rather, that a membrane-bound protein factor, whose thermal sensitivity is modified by changes in its phospholipid environment during temperature adaptation but not during photoperiod adaptation, is the primary site of heat injury."} {"id": "PMID:1263774", "title": "Effect of vitamin E deficiency on the lipid class and fatty acid composition of rat brain gray and white matter.", "content": "Three-week old male Sprague-Dawley rats were placed on a control or vitamin E-deficient diet for 9 months. The total lipid and cholesterol contents of brain gray and white matter areas in the vitamin E-deficient group did not differ from controls. The concentration of cerebrosides was lower in white matter but higher in gray matter of deficient animals. However, sulfatide was significantly (P less than 0.001) higher in white and gray matter of deficient animals compared with controls. Lysolecithin was not found in vitamin E-deficient gray matter but was present in control gray matter lipids. No marked differences were found in the concentrations or relative amounts of sphingomyelin, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, or phosphatidyl inositol in the phospholipids of gray or white matter of vitamin E-deficient rats as compared to controls. In addition, no remarkable differences were found in the fatty acid composition of total lipid extracts of gray or white matter from vitamin E-deficient rats when compared with controls.", "contents": "Effect of vitamin E deficiency on the lipid class and fatty acid composition of rat brain gray and white matter. Three-week old male Sprague-Dawley rats were placed on a control or vitamin E-deficient diet for 9 months. The total lipid and cholesterol contents of brain gray and white matter areas in the vitamin E-deficient group did not differ from controls. The concentration of cerebrosides was lower in white matter but higher in gray matter of deficient animals. However, sulfatide was significantly (P less than 0.001) higher in white and gray matter of deficient animals compared with controls. Lysolecithin was not found in vitamin E-deficient gray matter but was present in control gray matter lipids. No marked differences were found in the concentrations or relative amounts of sphingomyelin, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, or phosphatidyl inositol in the phospholipids of gray or white matter of vitamin E-deficient rats as compared to controls. In addition, no remarkable differences were found in the fatty acid composition of total lipid extracts of gray or white matter from vitamin E-deficient rats when compared with controls."} {"id": "PMID:1263775", "title": "Changes in phospholipids and acyl group composition of rat mammary gland during pregnant, lactating, and post-weaning periods.", "content": "The distribution of phospholipids as well as their fatty acid compositions of rat mammary tissues were examined during pregnant, lactating, and post-weaning periods. There was no apparent change in phospholipids and their acyl groups during the early and late pregnant periods. However, tissue phospholipid composition was different during pregnant, early, and late lactating periods. After parturition, there was a marked increase in the proportion of diacyl-glycerophosphorylcholine in the phospholipids of mammary tissue, but this proportion decreased gradually during lactation. The decrease in diacyl-glycerophosphorylcholine during lactation was marked by a corresponding increase in diacyl-glycerophosphorylethanolamie. Although the shorter chain fatty acids of triglycerides were increased during lactation, only a small proportion of these fatty acids was found in the phosphoglycerides. Marked changes in acyl group composition of individual phospholipids are found during these different physiological stages. In general, there was a rapid decrease in 20:4 and an increase in 18:2 in the major phosphoglycerides during parturition. The proportion of 20:4 in the phosphoglycerides remained low throughout the entire lactating period, while that of 18:2 continued to increase 2-3 fold. Most of the changes in acyl group of the phosphoglycerides during lactation returned to normal ca. 10 days after weaning. A possible relationship of the variation of phospholipid and acyl group compositions in mammary tissue to changes in hormonal pattern during different physiological stages is discussed.", "contents": "Changes in phospholipids and acyl group composition of rat mammary gland during pregnant, lactating, and post-weaning periods. The distribution of phospholipids as well as their fatty acid compositions of rat mammary tissues were examined during pregnant, lactating, and post-weaning periods. There was no apparent change in phospholipids and their acyl groups during the early and late pregnant periods. However, tissue phospholipid composition was different during pregnant, early, and late lactating periods. After parturition, there was a marked increase in the proportion of diacyl-glycerophosphorylcholine in the phospholipids of mammary tissue, but this proportion decreased gradually during lactation. The decrease in diacyl-glycerophosphorylcholine during lactation was marked by a corresponding increase in diacyl-glycerophosphorylethanolamie. Although the shorter chain fatty acids of triglycerides were increased during lactation, only a small proportion of these fatty acids was found in the phosphoglycerides. Marked changes in acyl group composition of individual phospholipids are found during these different physiological stages. In general, there was a rapid decrease in 20:4 and an increase in 18:2 in the major phosphoglycerides during parturition. The proportion of 20:4 in the phosphoglycerides remained low throughout the entire lactating period, while that of 18:2 continued to increase 2-3 fold. Most of the changes in acyl group of the phosphoglycerides during lactation returned to normal ca. 10 days after weaning. A possible relationship of the variation of phospholipid and acyl group compositions in mammary tissue to changes in hormonal pattern during different physiological stages is discussed."} {"id": "PMID:1263776", "title": "Lipid metabolism of the yellow clam, Mesodesma mactroides: I. Composition of the lipids.", "content": "The lipid composition of the yellow clam, Mesodesma mactroides, that lives in the northern beaches of the Buenos Aires province of Argentina was studied. The main nonpolar lipids are triglycerides and alkoxyglycerides. Phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl serine are the main phospholipids. The predominant fatty acids are 16:0, 16:1omega7, 18:0, 18:1omega9, 20:5omega3, and 22:6omega3. They are mainly provided by the clam's food and stored in the hepatopancreas. The content of polyunsaturated acids increases in summer together with an increase in nonpolar lipids and is correlative with an increase in phytoplankton in the sea water. Sexual maturity modifies the lipid composition of gametes.", "contents": "Lipid metabolism of the yellow clam, Mesodesma mactroides: I. Composition of the lipids. The lipid composition of the yellow clam, Mesodesma mactroides, that lives in the northern beaches of the Buenos Aires province of Argentina was studied. The main nonpolar lipids are triglycerides and alkoxyglycerides. Phosphatidyl choline, phosphatidyl ethanolamine, and phosphatidyl serine are the main phospholipids. The predominant fatty acids are 16:0, 16:1omega7, 18:0, 18:1omega9, 20:5omega3, and 22:6omega3. They are mainly provided by the clam's food and stored in the hepatopancreas. The content of polyunsaturated acids increases in summer together with an increase in nonpolar lipids and is correlative with an increase in phytoplankton in the sea water. Sexual maturity modifies the lipid composition of gametes."} {"id": "PMID:1263777", "title": "Nutritional effects of the cyclic monomers of methyl linolenate in the rat.", "content": "Low levels (0.0075, 0.0225, and 0.15%) of cyclic fatty acid methyl esters (greater than 98% pure) were incorporated into diets of weanling rats fed different levels of protein. Animals on low protein diets (8-10% casein) exhibited decreased wt gains and feed consumption with increasing levels of cyclic esters in their diets after 6 weeks. Liver enlargements due to a significant (P less than 0.01) accumulation of liver lipid were noted in animals receiving 0.15% cyclic fatty acid esters in their diets.", "contents": "Nutritional effects of the cyclic monomers of methyl linolenate in the rat. Low levels (0.0075, 0.0225, and 0.15%) of cyclic fatty acid methyl esters (greater than 98% pure) were incorporated into diets of weanling rats fed different levels of protein. Animals on low protein diets (8-10% casein) exhibited decreased wt gains and feed consumption with increasing levels of cyclic esters in their diets after 6 weeks. Liver enlargements due to a significant (P less than 0.01) accumulation of liver lipid were noted in animals receiving 0.15% cyclic fatty acid esters in their diets."} {"id": "PMID:1263831", "title": "Effects of oleic acid infusion on plasma free fatty acids and blood ketone bodies in the fasting rat.", "content": "Oleic acid emulsions stabilized with albumin were infused into fasted rats. Blood samples taken before and during infusion were analyzed for free fatty acids (FFA), ketone bodies, glucose, and insulin. Turnover rates of FFA and ketone bodies were also determined using constant infusion of radioactive tracers. During oleic acid infusions at a rate of 2 mumoles/min/100 g body weight, FFA concentrations increased for a short time and then decreased to preinfusion levels. The decreases in concentrations were due to decreases in the endogenous rates of appearance of FFA into the blood. When oleic acid was infused at a rate of 3.5 mumoles/min/100 g body weight, FFA concentrations increased and remained elevated throughout the infusion. Ketone body concentrations more than doubled during infusions at 2 and 3.5 mumoles/min/100 g body weight and showed no signs of decreasing even when FFA concentrations decreased. Insulin concentrations doubled during infusion and glucose concentrations decreased. Insulin injected during infusion had little effect on concentrations of FFA or ketone bodies. It was concluded that infusions of oleic acid inhibit adipose tissue lipolysis and increase blood ketone concentrations in intact fasted rats. The injection of insulin does not inhibit ketogenesis when blood FFA levels are maintained by infusion.", "contents": "Effects of oleic acid infusion on plasma free fatty acids and blood ketone bodies in the fasting rat. Oleic acid emulsions stabilized with albumin were infused into fasted rats. Blood samples taken before and during infusion were analyzed for free fatty acids (FFA), ketone bodies, glucose, and insulin. Turnover rates of FFA and ketone bodies were also determined using constant infusion of radioactive tracers. During oleic acid infusions at a rate of 2 mumoles/min/100 g body weight, FFA concentrations increased for a short time and then decreased to preinfusion levels. The decreases in concentrations were due to decreases in the endogenous rates of appearance of FFA into the blood. When oleic acid was infused at a rate of 3.5 mumoles/min/100 g body weight, FFA concentrations increased and remained elevated throughout the infusion. Ketone body concentrations more than doubled during infusions at 2 and 3.5 mumoles/min/100 g body weight and showed no signs of decreasing even when FFA concentrations decreased. Insulin concentrations doubled during infusion and glucose concentrations decreased. Insulin injected during infusion had little effect on concentrations of FFA or ketone bodies. It was concluded that infusions of oleic acid inhibit adipose tissue lipolysis and increase blood ketone concentrations in intact fasted rats. The injection of insulin does not inhibit ketogenesis when blood FFA levels are maintained by infusion."} {"id": "PMID:1263832", "title": "Metabolism of amino- and carboxyl-sequence immunoreactive parathyroid hormone in the bovine: evidence for peripheral cleavage of hormone.", "content": "Radioimmunoassays that detect specifically peptide sequences within either the biologically active amino region (N-assay) or inactive carboxyl region (C-assay) of parathyroid hormone (PTH) were used to evaluate the metabolism of PTH during and after infusion and injection of homogeneous (containing less than 0.1% hormonal fragments) intact bovine PTH (bPTH) into calves. During continuous infusions of hormone, when constant blood levels of immunoreactive PTH were reached, a dissociation between the concentrations of amino versus carboxyl immunoreactivity was observed; concentrations of hormone measured by the C-assay rose to a level of approximately three times higher than that measured by the N-assay. Analysis by gel filtration of immunoreactive PTH in plasma samples from calves after injection of hormone showed the rapid disappearance of intact hormone (N- and C-assays) and the appearance of a large fragment detected by the C-assay but not by the N-assay. The hormonal fragment lacked antigenic determinants within the amino peptide sequence required for biologic activity. No additional fragments of PTH were detected by gel filtration using the N- and C-assays. No detectable conversion of intact PTH to hormonal fragments occurred during incubation in vitro in bovine serum. The results are consistent with the concept that PTH is metabolized after entry into the circulation at peripheral sites located outside the vascular space, resulting in the rapid disappearance from blood of intact hormone and the appearance of a biologically inactive hormonal fragment(s). These studies done in calves agree with earlier studies done in dogs and man and point to the existence in mammals of common pathways for the peripheral metabolism of PTH.", "contents": "Metabolism of amino- and carboxyl-sequence immunoreactive parathyroid hormone in the bovine: evidence for peripheral cleavage of hormone. Radioimmunoassays that detect specifically peptide sequences within either the biologically active amino region (N-assay) or inactive carboxyl region (C-assay) of parathyroid hormone (PTH) were used to evaluate the metabolism of PTH during and after infusion and injection of homogeneous (containing less than 0.1% hormonal fragments) intact bovine PTH (bPTH) into calves. During continuous infusions of hormone, when constant blood levels of immunoreactive PTH were reached, a dissociation between the concentrations of amino versus carboxyl immunoreactivity was observed; concentrations of hormone measured by the C-assay rose to a level of approximately three times higher than that measured by the N-assay. Analysis by gel filtration of immunoreactive PTH in plasma samples from calves after injection of hormone showed the rapid disappearance of intact hormone (N- and C-assays) and the appearance of a large fragment detected by the C-assay but not by the N-assay. The hormonal fragment lacked antigenic determinants within the amino peptide sequence required for biologic activity. No additional fragments of PTH were detected by gel filtration using the N- and C-assays. No detectable conversion of intact PTH to hormonal fragments occurred during incubation in vitro in bovine serum. The results are consistent with the concept that PTH is metabolized after entry into the circulation at peripheral sites located outside the vascular space, resulting in the rapid disappearance from blood of intact hormone and the appearance of a biologically inactive hormonal fragment(s). These studies done in calves agree with earlier studies done in dogs and man and point to the existence in mammals of common pathways for the peripheral metabolism of PTH."} {"id": "PMID:1263833", "title": "Effect of alcohol administration on plasma growth hormone response to insulin-induced hypoglycemia.", "content": "Plasma growth hormone (HGH) response to insulin-induced hypoglycemia was assessed in a group of normal adult volunteers, with and without prior consumption of ethanol. A significant difference was found in peak HGH concentrations on the two occasions, indicating that prior consumption of ethanol attenuates the normal HGH response to insulin-induced hypoglycemia. It is suggested that ethanol may deplete catecholamine stores in the neurons of the ventromedial nucleus of the hypothalamus and may thereby impair secretion of growth hormone releasing factor. Under certain circumstances this could be of importance in the pathogenesis of alcohol-induced hypoglycemia.", "contents": "Effect of alcohol administration on plasma growth hormone response to insulin-induced hypoglycemia. Plasma growth hormone (HGH) response to insulin-induced hypoglycemia was assessed in a group of normal adult volunteers, with and without prior consumption of ethanol. A significant difference was found in peak HGH concentrations on the two occasions, indicating that prior consumption of ethanol attenuates the normal HGH response to insulin-induced hypoglycemia. It is suggested that ethanol may deplete catecholamine stores in the neurons of the ventromedial nucleus of the hypothalamus and may thereby impair secretion of growth hormone releasing factor. Under certain circumstances this could be of importance in the pathogenesis of alcohol-induced hypoglycemia."} {"id": "PMID:1263834", "title": "Comparative effects of glycerol and dextrose on porphyrin precursor excretion in acute intermittent porphyria.", "content": "The effects of dietary manipulations on excretion of the porphyrin precursors, delta-aminolevulinic acid (ALA), and porphobilinogen (PBG) were studied in eight patients with acute intermittent porphyria. Three diet periods of 9-17 days comprised each study. In each patient, a \"baseline\" protein, fat, and carbohydrate intake was kept constant throughout. In addition, during the first diet period each patient received 150 g dextrose; during the second, this was replaced by an isocaloric amount of neutral fat; and during the third, the fat was replaced by 150 g glycerol. In each of the patients, three comparisons of the effect of diet on both ALA and PBG excretion were made: (1) 300 g carbohydrate versus 150 g carbohydrate (dextrose versus fat), (2) 150 g carbohydrate + 150 g glycerol versus 150 g carbohydrate (glycerol versus fat), and (3) 300 g carbohydrate versus 150 g carbohydrate + 150 g glycerol (dextrose versus glycerol). For each of these three diet comparisons, there are sixteen individual comparisons possible for the effect of diet on porphyrin precursor excretion, eight for ALA and eight for PBG. Thus, the mean values for ALA and PBG excretions during each of the diet periods are statistically compared internally within each individual patient. Increasing carbohydrate intake from 150 g to 300 g by isocaloric substitution of dextrose for fat produced a significant (p less than 0.05) decline in eight of the sixteen comparisons of ALA and PBG excretion. Addition of 150 g glycerol by isocaloric substitution for fat caused a significant (p less than 0.05) decline in nine of the sixteen possible comparisons. In the sixteen comparisons of isocaloric dextrose and isocaloric glycerol-substituted diets, dextrose produced significantly (p less than 0.05) lower porphyrin precursor excretion in four cases and glycerol produced significantly (p less than 0.05) lower values in five. One patient showed no significant change on any of the diets. Of the four patients having symptoms believed referrable to porphyria during the study, three reported an improvement in symptoms during the high glycerol intake. The effects of dietary perturbations on porphyrin precursor excretion in acute intermittent porphyria are variable, but glycerol appears to be capable of decreasing the excretions and may prove useful in treating some of these patients.", "contents": "Comparative effects of glycerol and dextrose on porphyrin precursor excretion in acute intermittent porphyria. The effects of dietary manipulations on excretion of the porphyrin precursors, delta-aminolevulinic acid (ALA), and porphobilinogen (PBG) were studied in eight patients with acute intermittent porphyria. Three diet periods of 9-17 days comprised each study. In each patient, a \"baseline\" protein, fat, and carbohydrate intake was kept constant throughout. In addition, during the first diet period each patient received 150 g dextrose; during the second, this was replaced by an isocaloric amount of neutral fat; and during the third, the fat was replaced by 150 g glycerol. In each of the patients, three comparisons of the effect of diet on both ALA and PBG excretion were made: (1) 300 g carbohydrate versus 150 g carbohydrate (dextrose versus fat), (2) 150 g carbohydrate + 150 g glycerol versus 150 g carbohydrate (glycerol versus fat), and (3) 300 g carbohydrate versus 150 g carbohydrate + 150 g glycerol (dextrose versus glycerol). For each of these three diet comparisons, there are sixteen individual comparisons possible for the effect of diet on porphyrin precursor excretion, eight for ALA and eight for PBG. Thus, the mean values for ALA and PBG excretions during each of the diet periods are statistically compared internally within each individual patient. Increasing carbohydrate intake from 150 g to 300 g by isocaloric substitution of dextrose for fat produced a significant (p less than 0.05) decline in eight of the sixteen comparisons of ALA and PBG excretion. Addition of 150 g glycerol by isocaloric substitution for fat caused a significant (p less than 0.05) decline in nine of the sixteen possible comparisons. In the sixteen comparisons of isocaloric dextrose and isocaloric glycerol-substituted diets, dextrose produced significantly (p less than 0.05) lower porphyrin precursor excretion in four cases and glycerol produced significantly (p less than 0.05) lower values in five. One patient showed no significant change on any of the diets. Of the four patients having symptoms believed referrable to porphyria during the study, three reported an improvement in symptoms during the high glycerol intake. The effects of dietary perturbations on porphyrin precursor excretion in acute intermittent porphyria are variable, but glycerol appears to be capable of decreasing the excretions and may prove useful in treating some of these patients."} {"id": "PMID:1263835", "title": "Amino acid uptake and output by the sheep hind limb.", "content": "Arteriovenous differences across the hind limb of fed sheep show release of alanine, glutamine, and tyrosine and uptake of serine, glutamate, and possibly lysine. In starved animals there is a net output of most amino acids, although the amount of alanine released, 26 nmol/ml blood, is much lower than reported for human muscle and is less than the cumulative release of valine, leucine, and isoleucine. Since it has been argued that the carbon of alanine is derived from glucose and the nitrogen from the deamination of branched chain amino acids, we suggest that either nutrient availability is limiting alanine output or else sheep muscle has an impaired ability to degrade the branched chain amino acids.", "contents": "Amino acid uptake and output by the sheep hind limb. Arteriovenous differences across the hind limb of fed sheep show release of alanine, glutamine, and tyrosine and uptake of serine, glutamate, and possibly lysine. In starved animals there is a net output of most amino acids, although the amount of alanine released, 26 nmol/ml blood, is much lower than reported for human muscle and is less than the cumulative release of valine, leucine, and isoleucine. Since it has been argued that the carbon of alanine is derived from glucose and the nitrogen from the deamination of branched chain amino acids, we suggest that either nutrient availability is limiting alanine output or else sheep muscle has an impaired ability to degrade the branched chain amino acids."} {"id": "PMID:1263836", "title": "Renal hemodynamics and water excretion in Addison's disease.", "content": "Patients with Addison's disease have impaired ability to excrete free water. The mechanism of this defect is still not clear. These experiments were designed to help clarify the role of altered renal hemodynamics in the genesis of the defect. Six patients with Addison's disease were studied. Enough salt and water was administered to maintain adequate hydration throughout the study but no hormonal replacement was instituted. After a water load, the urine output (V), free water clearance (CH2O), sodium excretion (UNaV), total solute clearance (COsm), inulin clearance (CIn), and para-aminohippurate clearance (CPAH) were measured by standard clearance techniques. In the control studies V and CH2O were abnormally low. The studies were repeated after administration of DOCA, 2.5 mg daily, for a week. This medication decreased UNaV and improved the plasma electrolyte profile but did not cause a significant change in V, CH2O, GFR, or RPF. The same studies were repeated once more after administration of prednisone, 5 mg daily in divided doses, for a week. This drug induced a marked water diuresis while GFR and RPF remained unchanged. It is concluded that hypovolemia and altered renal hemodynamics are not the only mechanisms of the impaired water excretion in Addison's disease. A severe defect remains after normalization of hypovolemia and this is corrected by prednisone but not by DOCA, through mechanisms which do not involve changes in GFR or RPF.", "contents": "Renal hemodynamics and water excretion in Addison's disease. Patients with Addison's disease have impaired ability to excrete free water. The mechanism of this defect is still not clear. These experiments were designed to help clarify the role of altered renal hemodynamics in the genesis of the defect. Six patients with Addison's disease were studied. Enough salt and water was administered to maintain adequate hydration throughout the study but no hormonal replacement was instituted. After a water load, the urine output (V), free water clearance (CH2O), sodium excretion (UNaV), total solute clearance (COsm), inulin clearance (CIn), and para-aminohippurate clearance (CPAH) were measured by standard clearance techniques. In the control studies V and CH2O were abnormally low. The studies were repeated after administration of DOCA, 2.5 mg daily, for a week. This medication decreased UNaV and improved the plasma electrolyte profile but did not cause a significant change in V, CH2O, GFR, or RPF. The same studies were repeated once more after administration of prednisone, 5 mg daily in divided doses, for a week. This drug induced a marked water diuresis while GFR and RPF remained unchanged. It is concluded that hypovolemia and altered renal hemodynamics are not the only mechanisms of the impaired water excretion in Addison's disease. A severe defect remains after normalization of hypovolemia and this is corrected by prednisone but not by DOCA, through mechanisms which do not involve changes in GFR or RPF."} {"id": "PMID:1263837", "title": "Muscle nitrogen metabolism in chronic hepatic insufficiency.", "content": "Whole blood arterio-venous (A-V) differences for ammonia (NH3) and amino acids were determined across the forearm in 14 patients with decompensated alcoholic cirrhosis and hyperammonemia. NH3 was extracted by the forearm in all patients; however, the fractional extraction of NH3 was significantly less in five individuals with gross muscle wasting (13.3% versus 25.3%). There was neither a significant uptake nor release of NH3 in normal control subjects. The arterial concentrations of 12 out of 20 amino acids were strikingly diminished in the patient group. In contrast to normal subjects, in whom the release of alanine exceeds that of glutamine, the A-V difference for glutamine in the patients was threefold greater than that for alanine. The A-V differences for all other amino acids were not significantly different from zero. The results suggest that (1) muscle plays an important role in disposing of NH3 in patients with hepatic insufficiency and (2) a major fraction of NH3 taken up by muscle is released as glutamine.", "contents": "Muscle nitrogen metabolism in chronic hepatic insufficiency. Whole blood arterio-venous (A-V) differences for ammonia (NH3) and amino acids were determined across the forearm in 14 patients with decompensated alcoholic cirrhosis and hyperammonemia. NH3 was extracted by the forearm in all patients; however, the fractional extraction of NH3 was significantly less in five individuals with gross muscle wasting (13.3% versus 25.3%). There was neither a significant uptake nor release of NH3 in normal control subjects. The arterial concentrations of 12 out of 20 amino acids were strikingly diminished in the patient group. In contrast to normal subjects, in whom the release of alanine exceeds that of glutamine, the A-V difference for glutamine in the patients was threefold greater than that for alanine. The A-V differences for all other amino acids were not significantly different from zero. The results suggest that (1) muscle plays an important role in disposing of NH3 in patients with hepatic insufficiency and (2) a major fraction of NH3 taken up by muscle is released as glutamine."} {"id": "PMID:1263838", "title": "Free and total insulin levels in a patient with insulin-resistant diabetes mellitus and chronic lymphatic leukemia: effect of prednisone therapy.", "content": "An insulin-resistant diabetic patient who also has chronic lymphocytic leukemia and very high plasma levels of free and total insulin along with high levels of insulin antibodies is described. In response to prednisone therapy, his insulin requirement decreased, but the total and free insulin concentrations increased as insulin antibody measured as the maximal insulin-binding capacity of plasma remained unchanged. In insulin resistance, persistent hyperglycemia, in spite of high levels of immunoreactive free insulin, presumably reflects peripheral tissue unresponsiveness to insulin. The beneficial effect of prednisone treatment in this patient is discussed, and it is postulated to be the result of either increased availability of free insulin or an increased responsiveness of the tissues to insulin or both.", "contents": "Free and total insulin levels in a patient with insulin-resistant diabetes mellitus and chronic lymphatic leukemia: effect of prednisone therapy. An insulin-resistant diabetic patient who also has chronic lymphocytic leukemia and very high plasma levels of free and total insulin along with high levels of insulin antibodies is described. In response to prednisone therapy, his insulin requirement decreased, but the total and free insulin concentrations increased as insulin antibody measured as the maximal insulin-binding capacity of plasma remained unchanged. In insulin resistance, persistent hyperglycemia, in spite of high levels of immunoreactive free insulin, presumably reflects peripheral tissue unresponsiveness to insulin. The beneficial effect of prednisone treatment in this patient is discussed, and it is postulated to be the result of either increased availability of free insulin or an increased responsiveness of the tissues to insulin or both."} {"id": "PMID:1263839", "title": "Effect of protein intake and dialysis on the abnormal growth hormone, glucose, and insulin homeostasis in uremia.", "content": "To evaluate the role of protein intake in the altered growth hormone (GH) secretion of chronic renal failure, GH responses to mild exercise and to an oral glucose tolerance test were measured in ten uremic patients ingesting both low and normal protein diets. To delineate the effect of uremia on any interaction between GH and protein intake, tests were performed before dialysis, after daily dialyses for 3-4 days and after withholding dialysis for 3-4 days. Results were as follows: (1) exercise-stimulated GH release was increased compared to controls; (2) protein intake did not alter GH secretion, (3) basal GH concentrations were significantly correlated with creatinine levels and were significantly lower after dialysis, (4) dialysis did not improve the oral glucose tolerance test, (5) there was no correlation between glucose tolerance and exercise-stimulated GH levels, basal GH concentrations, or the sum of GH values after glucose, and (6) dialysis significantly increased the insulin response to glucose. In chronic renal failure enhanced GH secretion is not affected by protein intake, does not cause glucose intolerance, and may be related to the degree of uremia. Dialysis does not improve glucose tolerance, but does increase glucose-stimulated insulin release suggesting that insulin antagonism is not ameliorated.", "contents": "Effect of protein intake and dialysis on the abnormal growth hormone, glucose, and insulin homeostasis in uremia. To evaluate the role of protein intake in the altered growth hormone (GH) secretion of chronic renal failure, GH responses to mild exercise and to an oral glucose tolerance test were measured in ten uremic patients ingesting both low and normal protein diets. To delineate the effect of uremia on any interaction between GH and protein intake, tests were performed before dialysis, after daily dialyses for 3-4 days and after withholding dialysis for 3-4 days. Results were as follows: (1) exercise-stimulated GH release was increased compared to controls; (2) protein intake did not alter GH secretion, (3) basal GH concentrations were significantly correlated with creatinine levels and were significantly lower after dialysis, (4) dialysis did not improve the oral glucose tolerance test, (5) there was no correlation between glucose tolerance and exercise-stimulated GH levels, basal GH concentrations, or the sum of GH values after glucose, and (6) dialysis significantly increased the insulin response to glucose. In chronic renal failure enhanced GH secretion is not affected by protein intake, does not cause glucose intolerance, and may be related to the degree of uremia. Dialysis does not improve glucose tolerance, but does increase glucose-stimulated insulin release suggesting that insulin antagonism is not ameliorated."} {"id": "PMID:1263840", "title": "Thyrotropin levels in hyperlipidemic survivors of myocardial infarction.", "content": "In an earlier investigations, the prevalence of hyperlipidemia in a group of patients who survived myocardial infarction was determined, and family studies were performed to allow genetic classification of patients with hyperlipidemia. Radioimmunoassay for thyrotropin (TSH) has now been performed on plasmas from most of these hyperlipidemic survivors. Elevated TSH values were found in five of the 18 hyperlipidemic women over age 60, and in seven of the remaining 104 hyperlipidemic subjects. Among the various genetically defined types of hyperlipidemia, the highest prevalence of TSH elevations was seen in women with sporadic (nonfamilial) hypertriglyceridemia; four of the ten had an abnormal TSH level, and two of the remainder were receiving thyroid medication. Hypercholesterolemia was not strongly correlated with TSH abnormalities. These data support the hypothesis that clinically inapparent thyroid damage may be associated with coronary artery disease.", "contents": "Thyrotropin levels in hyperlipidemic survivors of myocardial infarction. In an earlier investigations, the prevalence of hyperlipidemia in a group of patients who survived myocardial infarction was determined, and family studies were performed to allow genetic classification of patients with hyperlipidemia. Radioimmunoassay for thyrotropin (TSH) has now been performed on plasmas from most of these hyperlipidemic survivors. Elevated TSH values were found in five of the 18 hyperlipidemic women over age 60, and in seven of the remaining 104 hyperlipidemic subjects. Among the various genetically defined types of hyperlipidemia, the highest prevalence of TSH elevations was seen in women with sporadic (nonfamilial) hypertriglyceridemia; four of the ten had an abnormal TSH level, and two of the remainder were receiving thyroid medication. Hypercholesterolemia was not strongly correlated with TSH abnormalities. These data support the hypothesis that clinically inapparent thyroid damage may be associated with coronary artery disease."} {"id": "PMID:1263841", "title": "Brain tryptophan, plasma free tryptophan and distribution of plasma neutral amino acids.", "content": "Although rat brain tryptophan is strikingly elevated following portacaval shunt, plasma total tryptophan is unchanged and plasma free tryptophan is not elevated to the same degree as brain tryptophan. Investigation of the concentrations of the neutral amino acids (phenylalanine, tyrosine, methionine, threonine, leucine, isoleucine, and valine) revealed that their distribution and the sum of their concentrations were altered following portacaval shunt, and that this pattern was similar to that seen in humans with cirrhosis of the liver. It is suggested that both the elevation in plasma free tryptophan and the decrease in the competing neutral amino acids, act together to increase the transport of tryptophan into brain when portal blood is diverted around the liver. The implications of these findings in therapy of hepatic coma is discussed.", "contents": "Brain tryptophan, plasma free tryptophan and distribution of plasma neutral amino acids. Although rat brain tryptophan is strikingly elevated following portacaval shunt, plasma total tryptophan is unchanged and plasma free tryptophan is not elevated to the same degree as brain tryptophan. Investigation of the concentrations of the neutral amino acids (phenylalanine, tyrosine, methionine, threonine, leucine, isoleucine, and valine) revealed that their distribution and the sum of their concentrations were altered following portacaval shunt, and that this pattern was similar to that seen in humans with cirrhosis of the liver. It is suggested that both the elevation in plasma free tryptophan and the decrease in the competing neutral amino acids, act together to increase the transport of tryptophan into brain when portal blood is diverted around the liver. The implications of these findings in therapy of hepatic coma is discussed."} {"id": "PMID:1263842", "title": "Parathyroid hormone and vertebral osteosclerosis in uremic patients.", "content": "Six out of 30 patients with chronic renal failure showed osteosclerosis in the lateral radiograph of the lumbar spine. When two groups with a similar degree of renal impairment were compared, the patients with osteosclerosis were younger and had a significantly higher level of circulating PTH (p less than 0.05) and total hydroxyproline excretion (p less than 0.02), than patients without overt osteosclerosis. The metacarpal cortical thickness was significantly reduced in patients with vertebral osteosclerosis. The results suggest that in patients with chronic uremia endogenous hypersecretion of PTH is one of the most significant factors responsible for the development of osteosclerosis. The mineral released from other skeletal sites could be utilized in the mineralization of the newly formed trabecular bone without any external calcium gain.", "contents": "Parathyroid hormone and vertebral osteosclerosis in uremic patients. Six out of 30 patients with chronic renal failure showed osteosclerosis in the lateral radiograph of the lumbar spine. When two groups with a similar degree of renal impairment were compared, the patients with osteosclerosis were younger and had a significantly higher level of circulating PTH (p less than 0.05) and total hydroxyproline excretion (p less than 0.02), than patients without overt osteosclerosis. The metacarpal cortical thickness was significantly reduced in patients with vertebral osteosclerosis. The results suggest that in patients with chronic uremia endogenous hypersecretion of PTH is one of the most significant factors responsible for the development of osteosclerosis. The mineral released from other skeletal sites could be utilized in the mineralization of the newly formed trabecular bone without any external calcium gain."} {"id": "PMID:1263843", "title": "Hyperprolactinemia influences renal function in man.", "content": "Renal handling of solute and water following oral water loading was determined in six subjects with small pituitary adenomas associated with nonsuppressible hyperprolactinemia. Compared to control subjects, urine volume and solute excretion were significantly diminished in the hyperprolactinemic group. This was attributable to a decrease in osmolar clearance. Free water clearances were not different from control subjects. Hypothyroidism and adrenal insufficiency as an explanation for the antidiuresis were excluded in each patient. The data supports the suggestion that prolactin influences renal function in man.", "contents": "Hyperprolactinemia influences renal function in man. Renal handling of solute and water following oral water loading was determined in six subjects with small pituitary adenomas associated with nonsuppressible hyperprolactinemia. Compared to control subjects, urine volume and solute excretion were significantly diminished in the hyperprolactinemic group. This was attributable to a decrease in osmolar clearance. Free water clearances were not different from control subjects. Hypothyroidism and adrenal insufficiency as an explanation for the antidiuresis were excluded in each patient. The data supports the suggestion that prolactin influences renal function in man."} {"id": "PMID:1263844", "title": "Utilization of oxidizable substrates by the sheep hind limb: effects of starvation and exercise.", "content": "Measurements of substrate uptake by the sheep hind limb show a pattern similar to human and other monogastric animals. Thus free fatty acids (FFA) are the principal substrates at rest and during exercise while beta-hydroxybutyrate and acetoacetate are major nutrients in starved animals. The hind limb has arteriovenous differences for glucose and lactate which indicate that glucose supplies about 27% of the fuel of respiration during exercise, but the hind limb in resting, fed, and starved animals returns essentially all of the glucose carbon to the blood in the form of lactate. This finding is consistent with a conservation of glucose in aminals which obtain very little dietary glucose. Although some acetate is extracted from the blood in fed sheep, the utilization of this nutrient can account for only 2% or less of the oxygen uptake in the hind limb of starved or exercising animals. Thus, while acetate is the major product of the sheep rumen it is not used directly as a major energy source. We propose that most of the actate is converted to FFA which can be stored as triglyceride or oxidized in muscle.", "contents": "Utilization of oxidizable substrates by the sheep hind limb: effects of starvation and exercise. Measurements of substrate uptake by the sheep hind limb show a pattern similar to human and other monogastric animals. Thus free fatty acids (FFA) are the principal substrates at rest and during exercise while beta-hydroxybutyrate and acetoacetate are major nutrients in starved animals. The hind limb has arteriovenous differences for glucose and lactate which indicate that glucose supplies about 27% of the fuel of respiration during exercise, but the hind limb in resting, fed, and starved animals returns essentially all of the glucose carbon to the blood in the form of lactate. This finding is consistent with a conservation of glucose in aminals which obtain very little dietary glucose. Although some acetate is extracted from the blood in fed sheep, the utilization of this nutrient can account for only 2% or less of the oxygen uptake in the hind limb of starved or exercising animals. Thus, while acetate is the major product of the sheep rumen it is not used directly as a major energy source. We propose that most of the actate is converted to FFA which can be stored as triglyceride or oxidized in muscle."} {"id": "PMID:1263845", "title": "Renal excretion of uric acid during prolonged fasting.", "content": "Serum and urine uric acid were evaluated during prolonged therapeutic fasting in 15 obese patients. With increasing ketonemia the serum uric acid rose from a control value of 5.9 +/- 0.4 to 12.5 +/- 1.0 mg/100 ml at 7 days and then decreased progressively to 7.7 +/- 1.3 mg/100 ml by 28 days despite sustained ketonemia. The uric acid clearance were 5.5 +/- 0.9, 1.8 +/- 0.2, and 4.4 +/- 1.5 ml/min at days 0, 7, and 25 of fasting. At the same times the creatinine clearances were 114 +/- 11, 80 +/- 6, and 64 +/- 6.3 ml/min. There was no evidence of a renal tubular abnormality as assessed by glycosuria, bicarbonaturia, or increased phosphaturia. Urate binding to plasma proteins remained unchanged. Acute studies of the renal handling of uric acid revealed a uricosuric response to the administration of sodium lactate or sodium bicarbonate by intravenous infusion and low-dose acetylsalicylic acid orally. This renal tubular response departs significantly from that observed during the overnight fasted state and could not be accounted for by extracellular fluid volume expansion or the induced acid-base changes.", "contents": "Renal excretion of uric acid during prolonged fasting. Serum and urine uric acid were evaluated during prolonged therapeutic fasting in 15 obese patients. With increasing ketonemia the serum uric acid rose from a control value of 5.9 +/- 0.4 to 12.5 +/- 1.0 mg/100 ml at 7 days and then decreased progressively to 7.7 +/- 1.3 mg/100 ml by 28 days despite sustained ketonemia. The uric acid clearance were 5.5 +/- 0.9, 1.8 +/- 0.2, and 4.4 +/- 1.5 ml/min at days 0, 7, and 25 of fasting. At the same times the creatinine clearances were 114 +/- 11, 80 +/- 6, and 64 +/- 6.3 ml/min. There was no evidence of a renal tubular abnormality as assessed by glycosuria, bicarbonaturia, or increased phosphaturia. Urate binding to plasma proteins remained unchanged. Acute studies of the renal handling of uric acid revealed a uricosuric response to the administration of sodium lactate or sodium bicarbonate by intravenous infusion and low-dose acetylsalicylic acid orally. This renal tubular response departs significantly from that observed during the overnight fasted state and could not be accounted for by extracellular fluid volume expansion or the induced acid-base changes."} {"id": "PMID:1263846", "title": "Human leukocyte peroxidase: activity of a soluble and membrane-bound enzyme form in normal persons and patients with neuronal ceroid-lipofuscinosis.", "content": "Human leukocytes contain a peroxidase fraction soluble in 0.1 M phosphate buffer and an insoluble peroxidase component with 10--15 times higher specific activity which can be extracted by 0.1 M phosphate buffer + 0.2% Triton X-100 + 0.2% sodium taurocholate and sonication. Both enzyme components have been estimated spectrophotometrically with the substrate hydrogen peroxide (final concentration 1 mM) and the hydrogen donor p-phenylenediamine (final concentration 28-55 mM) within the first 60 sec. The pH-optimum of the soluble and membrane-bound leukocyte peroxidase is at pH 7.0 with a second smaller peak at pH 5.5. Using 0.2 M boric acid/0.05 M sodium borate buffer (pH 7.6) instead of phosphate buffer a 40%-50% increase of enzyme activity can be achieved. In two patients with the juvenile form of neuronal ceroid-lipofuscinosis (type Spielmeyer-Vogt) the activity of soluble leukocyte peroxidase was considerably reduced, in one patient with the late infantile form (type Jansky-Bielschowsky) the activity was just below the normal range, and in two patients with the adult form (type Kuf) activity was normal. In all patients the activity of membrane-bound leukocyte peroxidase was not significantly altered. Only one of four heterozygotes for the juvenile type had deficient values of the soluble enzyme. The variability of the peroxidase findings in patients and carriers with neuronal ceroid-lipofuscinosis make it uncertain whether this represents the primary enzymic defect.", "contents": "Human leukocyte peroxidase: activity of a soluble and membrane-bound enzyme form in normal persons and patients with neuronal ceroid-lipofuscinosis. Human leukocytes contain a peroxidase fraction soluble in 0.1 M phosphate buffer and an insoluble peroxidase component with 10--15 times higher specific activity which can be extracted by 0.1 M phosphate buffer + 0.2% Triton X-100 + 0.2% sodium taurocholate and sonication. Both enzyme components have been estimated spectrophotometrically with the substrate hydrogen peroxide (final concentration 1 mM) and the hydrogen donor p-phenylenediamine (final concentration 28-55 mM) within the first 60 sec. The pH-optimum of the soluble and membrane-bound leukocyte peroxidase is at pH 7.0 with a second smaller peak at pH 5.5. Using 0.2 M boric acid/0.05 M sodium borate buffer (pH 7.6) instead of phosphate buffer a 40%-50% increase of enzyme activity can be achieved. In two patients with the juvenile form of neuronal ceroid-lipofuscinosis (type Spielmeyer-Vogt) the activity of soluble leukocyte peroxidase was considerably reduced, in one patient with the late infantile form (type Jansky-Bielschowsky) the activity was just below the normal range, and in two patients with the adult form (type Kuf) activity was normal. In all patients the activity of membrane-bound leukocyte peroxidase was not significantly altered. Only one of four heterozygotes for the juvenile type had deficient values of the soluble enzyme. The variability of the peroxidase findings in patients and carriers with neuronal ceroid-lipofuscinosis make it uncertain whether this represents the primary enzymic defect."} {"id": "PMID:1263847", "title": "Effect of hypophysectomy on weight gain and body composition in the genetically obese yellow (Ay/a) mouse.", "content": "In order to investigate the role of the pituitary in yellow obesity, genetically obese yellow mice (Aya) and normal nonyellow siblings (aa) were either shamoperated or hypophysectomized by a paraphyarngeal method at 45--50 days of age. The operated animals were weighed for 13 wk and their carcasses subsequently were analyzed for fat, water, and lean body mass content. Completeness of hypophysectomy was assessed by microscopic examination of stained serial sections of the brain and attached hypophyseal capsule. Completely hypophysectomized Aya mice still gained more weight than hypophysectomized nonyellow siblings and showed the excessive accumulation of fat characteristic of the yellow obesity. We conclude that the pituitary and the endocrine pathways it controls are not primarily involved in the expression of yellow obesity.", "contents": "Effect of hypophysectomy on weight gain and body composition in the genetically obese yellow (Ay/a) mouse. In order to investigate the role of the pituitary in yellow obesity, genetically obese yellow mice (Aya) and normal nonyellow siblings (aa) were either shamoperated or hypophysectomized by a paraphyarngeal method at 45--50 days of age. The operated animals were weighed for 13 wk and their carcasses subsequently were analyzed for fat, water, and lean body mass content. Completeness of hypophysectomy was assessed by microscopic examination of stained serial sections of the brain and attached hypophyseal capsule. Completely hypophysectomized Aya mice still gained more weight than hypophysectomized nonyellow siblings and showed the excessive accumulation of fat characteristic of the yellow obesity. We conclude that the pituitary and the endocrine pathways it controls are not primarily involved in the expression of yellow obesity."} {"id": "PMID:1263882", "title": "Self-descriptions of applicants to medical school.", "content": "An analysis of self-descriptive essays by applicants who successfully gained entry to medical school shows that five sub-types of entrant can be differentiated. Medical schools have not yet deliberated on the sort, or sorts, of person most needed in the medical profession, but doubtless individual selectors exercise personal if undeclared preferences.", "contents": "Self-descriptions of applicants to medical school. An analysis of self-descriptive essays by applicants who successfully gained entry to medical school shows that five sub-types of entrant can be differentiated. Medical schools have not yet deliberated on the sort, or sorts, of person most needed in the medical profession, but doubtless individual selectors exercise personal if undeclared preferences."} {"id": "PMID:1263883", "title": "A partially self-instructional system that any teacher can develop and implement.", "content": "Some authors have suggested that the teacher has two basic choices of style which can be used to influence learning: he/she can manage learning resources or he/she can function as such a resource. Part of the appeal for the authors of the course format described here is the blurring of that distinction. Functioning both as a manager and a resource appears to us a near optimal role for the teacher.", "contents": "A partially self-instructional system that any teacher can develop and implement. Some authors have suggested that the teacher has two basic choices of style which can be used to influence learning: he/she can manage learning resources or he/she can function as such a resource. Part of the appeal for the authors of the course format described here is the blurring of that distinction. Functioning both as a manager and a resource appears to us a near optimal role for the teacher."} {"id": "PMID:1263884", "title": "Medical student evaluation in the absence of examinations.", "content": "Traditional examination systems achieve a high degree of pseudo-precision, producing relatively little information that is constructively useful for student or teachers, and conveying it in the form of scores and marks that appear falsely accurate. The rationale and methodology of a structured evaluation system, in the absence of formal examinations, and based on validated self-assessment, are described. An account of the organization and uses of such a process, and a description of some new evaluation techniques used, is based on the system currently being evolved in the McMaster University M.D. Programme.", "contents": "Medical student evaluation in the absence of examinations. Traditional examination systems achieve a high degree of pseudo-precision, producing relatively little information that is constructively useful for student or teachers, and conveying it in the form of scores and marks that appear falsely accurate. The rationale and methodology of a structured evaluation system, in the absence of formal examinations, and based on validated self-assessment, are described. An account of the organization and uses of such a process, and a description of some new evaluation techniques used, is based on the system currently being evolved in the McMaster University M.D. Programme."} {"id": "PMID:1263885", "title": "Multiple choice questions: to guess or not to guess.", "content": "Multiple choice question papers in which the student has a 'don't know' option are widely used in undergraduate and postgraduate examinations in Medicine. In the present study students' performance in papers with a 'don't know' option has been compared with their performance when they are instructed to answer all the questions. By completing questions left unanswered (i.e. 'don't know' options) students were able to increase their score significantly and the rank order of the students in class is changed. Answers omitted may indicate complete ignorance or various degrees of knowledge. It is concluded that the 'don't know' option in multiple choice question papers favours the bold and test-wise student and in consequence their validity as a measure of achievement may suffer. Papers in which the student is instructed to answer all the questions are to be preferred to those in common use where there is a 'don't know' option.", "contents": "Multiple choice questions: to guess or not to guess. Multiple choice question papers in which the student has a 'don't know' option are widely used in undergraduate and postgraduate examinations in Medicine. In the present study students' performance in papers with a 'don't know' option has been compared with their performance when they are instructed to answer all the questions. By completing questions left unanswered (i.e. 'don't know' options) students were able to increase their score significantly and the rank order of the students in class is changed. Answers omitted may indicate complete ignorance or various degrees of knowledge. It is concluded that the 'don't know' option in multiple choice question papers favours the bold and test-wise student and in consequence their validity as a measure of achievement may suffer. Papers in which the student is instructed to answer all the questions are to be preferred to those in common use where there is a 'don't know' option."} {"id": "PMID:1263886", "title": "Upstairs, downstairs: medical students in their first clinical year and their previous experience of work in hospitals.", "content": "In a study of Edinburgh students in their first clinical year it was found that a sizeable proportion had had some prior experience of hospital life and work from vacation jobs--such as being porters, auxiliary nurses and so on. Students' retrospective accounts of such experience are reported. The most salient aspect of hospitals seen from this vantage point concerned the division of labour between grades of staff, and the hierarchical organization of hospital personnel. Students saw the experience primarily as a chance to see medicine 'from the other side'. It is suggested that such experiences can be drawn on in the teaching of sociology to undergraduate students.", "contents": "Upstairs, downstairs: medical students in their first clinical year and their previous experience of work in hospitals. In a study of Edinburgh students in their first clinical year it was found that a sizeable proportion had had some prior experience of hospital life and work from vacation jobs--such as being porters, auxiliary nurses and so on. Students' retrospective accounts of such experience are reported. The most salient aspect of hospitals seen from this vantage point concerned the division of labour between grades of staff, and the hierarchical organization of hospital personnel. Students saw the experience primarily as a chance to see medicine 'from the other side'. It is suggested that such experiences can be drawn on in the teaching of sociology to undergraduate students."} {"id": "PMID:1263887", "title": "A performance-based method of student evaluation.", "content": "A method of medical education has been developed which emphasizes audit of student performance in terms of behavioural traits (thoroughness, reliability, analytic sense, and efficiency) rather than in terms of memorized knowledge. This method is dependent upon the Problem-Oriented Medical Record. The tools developed for the audit and some preliminary results are presented.", "contents": "A performance-based method of student evaluation. A method of medical education has been developed which emphasizes audit of student performance in terms of behavioural traits (thoroughness, reliability, analytic sense, and efficiency) rather than in terms of memorized knowledge. This method is dependent upon the Problem-Oriented Medical Record. The tools developed for the audit and some preliminary results are presented."} {"id": "PMID:1263888", "title": "Methods of attitude assessment for medical teachers.", "content": "A variety of methods to assess attitudes toward patient care, the medical profession and medical education have been described. Direct, written methods have been most widespread; they are most useful with anonymous respondents when group, rather than individual, data are sought. Examples of disguised, written and audio-visual methods were also presented to stimulate readers to experiment with these approaches. Finally, observational methods were reviewed to capture behaviours in real and simulated situations that reflect attitudes.", "contents": "Methods of attitude assessment for medical teachers. A variety of methods to assess attitudes toward patient care, the medical profession and medical education have been described. Direct, written methods have been most widespread; they are most useful with anonymous respondents when group, rather than individual, data are sought. Examples of disguised, written and audio-visual methods were also presented to stimulate readers to experiment with these approaches. Finally, observational methods were reviewed to capture behaviours in real and simulated situations that reflect attitudes."} {"id": "PMID:1263889", "title": "Trainees assessment of vocational training in psychiatry: a pilot study at the Maudsley Hospital.", "content": "The adequacy of postgraduate trainees is assessed rather more frequently than that of the teaching process. A survey was therefore undertaken of the views of sixty-two junior psychiatrists regarding the clinical units they had worked on during their 3-year rotational training programme at the Maudsley Hospital. The quality of the training experience was felt to be related to work load (not too light), to the number of trainees attached to each consultant, and to the attention given by the consultant to instruction on practical management. The factors felt to need most attention were feedback from consultants on the trainee's performance, and the standards of academic instruction and of interdisciplinary teamwork.", "contents": "Trainees assessment of vocational training in psychiatry: a pilot study at the Maudsley Hospital. The adequacy of postgraduate trainees is assessed rather more frequently than that of the teaching process. A survey was therefore undertaken of the views of sixty-two junior psychiatrists regarding the clinical units they had worked on during their 3-year rotational training programme at the Maudsley Hospital. The quality of the training experience was felt to be related to work load (not too light), to the number of trainees attached to each consultant, and to the attention given by the consultant to instruction on practical management. The factors felt to need most attention were feedback from consultants on the trainee's performance, and the standards of academic instruction and of interdisciplinary teamwork."} {"id": "PMID:1263891", "title": "Medical education in France, Germany, Italy and the United Kingdom compared.", "content": "1. The purpose of the visit was to compare postgraduate medical education and training in the United Kingdom with that in France, the Federal Republic of Germany, and Italy. 2. Except in Italy, there appeared to be widespread agreement that specific postgraduate training for general practitioners was essential to improve the quality of practice and to relieve the undergraduate curriculum from the necessity to provide comprehensive medical training to prepare a graduate for independent practice. The main difficulty appeared to be the development of good 'teaching' practices. 3. Direct comparison between training programmes for specialist practice is not straightforward in view of the different staffing structure in continental hospitals and the existence of private specialist practice to which patients have direct access. Training appears to be generally longer in the United Kingdom, possibly due to the necessity of passing postgraduate diploma examinations, but outside the university hospitals the fully trained specialist (consultant) enjoys a higher status and independence than most hospital specialists in other countries. The absence of equivalent bodies to the Royal Colleges and Faculties places responsibility upon universities for specialist training on the continent; standards are not coordinated nationally, and vary significantly from region to region. 4. The need for continuing medical education for all doctors is accepted; this is essentially voluntary, although there are variable direct and indirect incentives. Programmes are organized on a local or regional basis in most countries, but in Germany and the U.K. there is a growing trend towards national coordination of both training programmes and the provision of continuing education. 5. The recent reorganization of the National Health Service in the United Kingdom provides opportunities for 'public health' doctors to become involved in the coordination of clinical services and to relate these to the needs of the public at large, as well as to provide preventive health services. These opportunities do not exist in France, Germany and Italy, where public health services remain discrete from clinical medicine, and postgraduate training is largely confined to formal teaching at designated institutes which are university based only in Italy. Opportunities for university staff to become involved in the organization and delivery of health care appear to be greater, therefore, in the United Kingdom than in other countries.", "contents": "Medical education in France, Germany, Italy and the United Kingdom compared. 1. The purpose of the visit was to compare postgraduate medical education and training in the United Kingdom with that in France, the Federal Republic of Germany, and Italy. 2. Except in Italy, there appeared to be widespread agreement that specific postgraduate training for general practitioners was essential to improve the quality of practice and to relieve the undergraduate curriculum from the necessity to provide comprehensive medical training to prepare a graduate for independent practice. The main difficulty appeared to be the development of good 'teaching' practices. 3. Direct comparison between training programmes for specialist practice is not straightforward in view of the different staffing structure in continental hospitals and the existence of private specialist practice to which patients have direct access. Training appears to be generally longer in the United Kingdom, possibly due to the necessity of passing postgraduate diploma examinations, but outside the university hospitals the fully trained specialist (consultant) enjoys a higher status and independence than most hospital specialists in other countries. The absence of equivalent bodies to the Royal Colleges and Faculties places responsibility upon universities for specialist training on the continent; standards are not coordinated nationally, and vary significantly from region to region. 4. The need for continuing medical education for all doctors is accepted; this is essentially voluntary, although there are variable direct and indirect incentives. Programmes are organized on a local or regional basis in most countries, but in Germany and the U.K. there is a growing trend towards national coordination of both training programmes and the provision of continuing education. 5. The recent reorganization of the National Health Service in the United Kingdom provides opportunities for 'public health' doctors to become involved in the coordination of clinical services and to relate these to the needs of the public at large, as well as to provide preventive health services. These opportunities do not exist in France, Germany and Italy, where public health services remain discrete from clinical medicine, and postgraduate training is largely confined to formal teaching at designated institutes which are university based only in Italy. Opportunities for university staff to become involved in the organization and delivery of health care appear to be greater, therefore, in the United Kingdom than in other countries."} {"id": "PMID:1263892", "title": "Correlation between students' results in pre-clinical and final surgery examinations.", "content": "The results obtained in each subject of the first 4 years of a 6 year course in medicine were assessed and compared with the final result obtained in surgery together with the result from a class test in surgery at the beginning of the fifth year. Two hundred and thirty-five students graduating between 1969 and 1973 were assessed, the correlations being tested with regression techniques. There was a highly significant degree of correlation between the final surgery result and all the previous records. However, there was a wide scatter of results, and the predictive value for the individual student was imprecise.", "contents": "Correlation between students' results in pre-clinical and final surgery examinations. The results obtained in each subject of the first 4 years of a 6 year course in medicine were assessed and compared with the final result obtained in surgery together with the result from a class test in surgery at the beginning of the fifth year. Two hundred and thirty-five students graduating between 1969 and 1973 were assessed, the correlations being tested with regression techniques. There was a highly significant degree of correlation between the final surgery result and all the previous records. However, there was a wide scatter of results, and the predictive value for the individual student was imprecise."} {"id": "PMID:1263893", "title": "The final examination in United Kingdom medical schools, 1974.", "content": "The structure, character and results of the final M.B. examinations held in United Kingdom medical schools in 1974 were investigated by postal questionnaire. The mean failure rate (10-5%, range 0-24-6%) was significantly higher in the student sample from the London medical schools compared with those in the periphery. No significant sex difference in total failure rate was noted. Wide variations were observed in the length and character of the examinations.", "contents": "The final examination in United Kingdom medical schools, 1974. The structure, character and results of the final M.B. examinations held in United Kingdom medical schools in 1974 were investigated by postal questionnaire. The mean failure rate (10-5%, range 0-24-6%) was significantly higher in the student sample from the London medical schools compared with those in the periphery. No significant sex difference in total failure rate was noted. Wide variations were observed in the length and character of the examinations."} {"id": "PMID:1263895", "title": "The effect of a spaced sex education course on medical students' sexual knowledge and attitudes.", "content": "This paper reviews the literature and emphasizes the rapid expansion of medical sex education, which has created a diversity of course content, curriculum timing and strategies. One variable of medical sex education programmes is whether they are massed or spaced courses. The authors conducted testing on 159 first year medical students who took a spaced sex education course. Significant changes in cognitive knowledge as well as attitudinal tolerance of others is reported. No changes were found in styles of thinking as measured by the Rokeach Dogmatism Scale.", "contents": "The effect of a spaced sex education course on medical students' sexual knowledge and attitudes. This paper reviews the literature and emphasizes the rapid expansion of medical sex education, which has created a diversity of course content, curriculum timing and strategies. One variable of medical sex education programmes is whether they are massed or spaced courses. The authors conducted testing on 159 first year medical students who took a spaced sex education course. Significant changes in cognitive knowledge as well as attitudinal tolerance of others is reported. No changes were found in styles of thinking as measured by the Rokeach Dogmatism Scale."} {"id": "PMID:1263897", "title": "Doctor-patient communication in general practice consultations.", "content": "Detailed study of a series of tape-recorded interviews enabled the author to carry out a critical self-audit of his consultations. The analysis of categories of verbal interaction in doctor-patient consultations proved to be a practical and reliable method of studying the doctor-patient relationship. The methods and techniques used in this research could, with advantage, be employed in the fields of undergraduate and postgraduate teaching. Since a satisfactory doctor-patient relationship is of great value, study in depth of the verbal interaction between doctor and patient in general practice consultations can provide guide lines to those who seek an improvement in doctor-patient communication.", "contents": "Doctor-patient communication in general practice consultations. Detailed study of a series of tape-recorded interviews enabled the author to carry out a critical self-audit of his consultations. The analysis of categories of verbal interaction in doctor-patient consultations proved to be a practical and reliable method of studying the doctor-patient relationship. The methods and techniques used in this research could, with advantage, be employed in the fields of undergraduate and postgraduate teaching. Since a satisfactory doctor-patient relationship is of great value, study in depth of the verbal interaction between doctor and patient in general practice consultations can provide guide lines to those who seek an improvement in doctor-patient communication."} {"id": "PMID:1263898", "title": "What should be taught in anatomy?", "content": "The aim of the undergraduate course in topographical anatomy should be to enable the student more meaningfully to carry out a physical medical examination, and to become familiar with the normal, thus providing the intellectual and technical background for later study of the abnormal. Attendance at postgraduate courses should be compulsory for admission to postgraduate surgical examinations; such courses should be complementary, not supplementary, to undergraduate courses.", "contents": "What should be taught in anatomy? The aim of the undergraduate course in topographical anatomy should be to enable the student more meaningfully to carry out a physical medical examination, and to become familiar with the normal, thus providing the intellectual and technical background for later study of the abnormal. Attendance at postgraduate courses should be compulsory for admission to postgraduate surgical examinations; such courses should be complementary, not supplementary, to undergraduate courses."} {"id": "PMID:1263901", "title": "The value of ordinary and advanced level British school-leaving examination results in predicting medical students' academic performance.", "content": "This paper examines the correlation between students' school-leaving examination results and medical school examination results, and discusses the usefulness of O and A level examination results as predictors of a student's ability to pass pre-clinical examinations in anatomy, physiology and biochemistry.", "contents": "The value of ordinary and advanced level British school-leaving examination results in predicting medical students' academic performance. This paper examines the correlation between students' school-leaving examination results and medical school examination results, and discusses the usefulness of O and A level examination results as predictors of a student's ability to pass pre-clinical examinations in anatomy, physiology and biochemistry."} {"id": "PMID:1263902", "title": "Student test type preference and its relation to personality and achievement.", "content": "1. Test type preference of 227 medical students was investigated by means of a questionnaire. 2. A majority of students believed that MCQ examinations gave rise to less advance anxiety than other forms of examination. 3. There was a highly significant correlation between preference and performance, probably as a result of reciprocal reinforcement between them. 4. A multiple linear regression analysis revealed than the scales stability/neuroticism, extraversion/introversion, general mental ability and native language had a significant influence on test preference. There was a significant trend for confident, stable students to demonstrate preference for MCQ while tense, anxious students tended to prefer other test types. 5. We conclude that a mixed examination format is desirable not only on theoretical grounds, but was also preferred by these students.", "contents": "Student test type preference and its relation to personality and achievement. 1. Test type preference of 227 medical students was investigated by means of a questionnaire. 2. A majority of students believed that MCQ examinations gave rise to less advance anxiety than other forms of examination. 3. There was a highly significant correlation between preference and performance, probably as a result of reciprocal reinforcement between them. 4. A multiple linear regression analysis revealed than the scales stability/neuroticism, extraversion/introversion, general mental ability and native language had a significant influence on test preference. There was a significant trend for confident, stable students to demonstrate preference for MCQ while tense, anxious students tended to prefer other test types. 5. We conclude that a mixed examination format is desirable not only on theoretical grounds, but was also preferred by these students."} {"id": "PMID:1263904", "title": "Patient monitoring in the operating room--an anesthetist's viewpoint.", "content": "The spectrum of patient monitoring techniques and equipment presently available in the operating room is reviewed from the anesthetist's viewpoint. Although electronic monitoring instruments are becoming more sophisticated with self-contained microprocessors or computer interfaces, few are designed for performance specifically within the hostile environment of the operating room. Intraoperative patient monitoring equipment lacks interchangeable transducers, facilities for automatic collection of physiological data, and methods for the display of trends in the patient's condition. Event recording during anesthesia depends upon the time-honored but inefficient handmade record of the anesthetist. Within the context of developing a computer-assisted monitoring and display system, this commentary presents the physician's perspective of instrumentation limitation and successes.", "contents": "Patient monitoring in the operating room--an anesthetist's viewpoint. The spectrum of patient monitoring techniques and equipment presently available in the operating room is reviewed from the anesthetist's viewpoint. Although electronic monitoring instruments are becoming more sophisticated with self-contained microprocessors or computer interfaces, few are designed for performance specifically within the hostile environment of the operating room. Intraoperative patient monitoring equipment lacks interchangeable transducers, facilities for automatic collection of physiological data, and methods for the display of trends in the patient's condition. Event recording during anesthesia depends upon the time-honored but inefficient handmade record of the anesthetist. Within the context of developing a computer-assisted monitoring and display system, this commentary presents the physician's perspective of instrumentation limitation and successes."} {"id": "PMID:1263906", "title": "Future trends in neurosurgical instrumentation--a speculative approach.", "content": "The neurosurgeon is confronted with a cumbersome array of sophisticated instrumentation with which he must cope. A multitude of tubes, wires, and cables spill about his feet and operative field, cluttering his work area and limiting his mobility. In this communication, the consolidation of power sources, improvement in the power delivery systems to the operative site, and the creation of an equipment console incorporating built-in lights, microscope, power sources, vital-sign monitors, and instrumentation are considered. The physiological condition and milieu of the surgeon are also examined. An attempt is made to outline some of the complex and provocative problems involved in improving the surgeon's physical work environment and in improving his instrumentation.", "contents": "Future trends in neurosurgical instrumentation--a speculative approach. The neurosurgeon is confronted with a cumbersome array of sophisticated instrumentation with which he must cope. A multitude of tubes, wires, and cables spill about his feet and operative field, cluttering his work area and limiting his mobility. In this communication, the consolidation of power sources, improvement in the power delivery systems to the operative site, and the creation of an equipment console incorporating built-in lights, microscope, power sources, vital-sign monitors, and instrumentation are considered. The physiological condition and milieu of the surgeon are also examined. An attempt is made to outline some of the complex and provocative problems involved in improving the surgeon's physical work environment and in improving his instrumentation."} {"id": "PMID:1263905", "title": "Improving radiology in surgery.", "content": "The time has come to reevaluate the use of films of substandard quality obtained from outdated radiography equipment. The authors recommend that surgical subspecialists, orthopedic surgeons, emergency room physicians, gastroenterologists, or whoever employs radiology in the operating room ensure that technological progress in radiology be transferred to the surgical area. The mobile C-arm image amplifier with television fluoroscopy and single-image storage device should be considered for orthopedic surgery and ER rooms. More sophisticated equipment is required for operative cholangiography and operative angiography.", "contents": "Improving radiology in surgery. The time has come to reevaluate the use of films of substandard quality obtained from outdated radiography equipment. The authors recommend that surgical subspecialists, orthopedic surgeons, emergency room physicians, gastroenterologists, or whoever employs radiology in the operating room ensure that technological progress in radiology be transferred to the surgical area. The mobile C-arm image amplifier with television fluoroscopy and single-image storage device should be considered for orthopedic surgery and ER rooms. More sophisticated equipment is required for operative cholangiography and operative angiography."} {"id": "PMID:1263908", "title": "Design hazards of electrosurgical devices.", "content": "The tremendous lifesaving value of adjunct electrosurgery to the medical profession is not without potential hazards. The hazards, which can be classified as radio-frequency burn hazards, shock hazards, electrocution hazards, and explosion hazards, may result from equipment design circuitry, possible failure modes, or operator error. The three basic electrosurgery systems currently being marketed--grounded output systems, referred-to-ground output systems, and floating output systems--are described, and the hazard potential of each system, as well as the hazard potentials of modifications of these systems, are identified. The authors propose a safety system to eliminate most of the hazards cited for the other systems, recommend minimum circuit performance requirements, and evaluate an electrosurgery standard.", "contents": "Design hazards of electrosurgical devices. The tremendous lifesaving value of adjunct electrosurgery to the medical profession is not without potential hazards. The hazards, which can be classified as radio-frequency burn hazards, shock hazards, electrocution hazards, and explosion hazards, may result from equipment design circuitry, possible failure modes, or operator error. The three basic electrosurgery systems currently being marketed--grounded output systems, referred-to-ground output systems, and floating output systems--are described, and the hazard potential of each system, as well as the hazard potentials of modifications of these systems, are identified. The authors propose a safety system to eliminate most of the hazards cited for the other systems, recommend minimum circuit performance requirements, and evaluate an electrosurgery standard."} {"id": "PMID:1263911", "title": "Trends in operating room devices.", "content": "Although trends in the use of operating room devices have generally followed advances in technology, the trends are not always influenced as much by surgical need as they are by industrial expediency and commercial promotion. Nonetheless, a broad view of trends in OR devices definitely points to efforts at greater compatibility between devices made by different manufacturers. To mention a few examples, operating tables are being made more compatible with OR X-ray equipment; surgical lighting is being designed for greater compatibility with air-handling systems and video equipment; power consoles have reduced the clutter of tubes, hoses, and wires in complicated operations, and have become more functional in keeping with the trend away from electrical power and toward nitrogen power for driving surgical tools; cabinetry is being designed to employ clean-air principles; and surgical apparel and barrier materials are undergoing close scrutiny for their effectiveness against moist bacterial strike-through in lengthy wet operations. Operating room devices form an important segment of the devices classified by the FDA, and are expected to benefit by the application of standards in performance and safety. This trend will affect not only the devices themselves, but all other facets of operating room design and engineering.", "contents": "Trends in operating room devices. Although trends in the use of operating room devices have generally followed advances in technology, the trends are not always influenced as much by surgical need as they are by industrial expediency and commercial promotion. Nonetheless, a broad view of trends in OR devices definitely points to efforts at greater compatibility between devices made by different manufacturers. To mention a few examples, operating tables are being made more compatible with OR X-ray equipment; surgical lighting is being designed for greater compatibility with air-handling systems and video equipment; power consoles have reduced the clutter of tubes, hoses, and wires in complicated operations, and have become more functional in keeping with the trend away from electrical power and toward nitrogen power for driving surgical tools; cabinetry is being designed to employ clean-air principles; and surgical apparel and barrier materials are undergoing close scrutiny for their effectiveness against moist bacterial strike-through in lengthy wet operations. Operating room devices form an important segment of the devices classified by the FDA, and are expected to benefit by the application of standards in performance and safety. This trend will affect not only the devices themselves, but all other facets of operating room design and engineering."} {"id": "PMID:1263907", "title": "Laser medical instrumentation.", "content": "In spite of inadequate budgets, significant research and development studies have been made on laser medical instrumentation applications for both diagnosis and treatment. Diagnostic instrumentation includes the laser microprobe for cation microanalyses, cytofluorometry, interferometry, transillumination, holography and acoustical holography, and communications and information handling. Laser investigative surgical instrumentation includes lasers of argon, carbon dioxide, neodymium-YAG, and ruby, which are used as optical scalpels. Advantages of laser surgical instrumentation include precision, color absorption for lasers in the visible light range, and hemostasis.", "contents": "Laser medical instrumentation. In spite of inadequate budgets, significant research and development studies have been made on laser medical instrumentation applications for both diagnosis and treatment. Diagnostic instrumentation includes the laser microprobe for cation microanalyses, cytofluorometry, interferometry, transillumination, holography and acoustical holography, and communications and information handling. Laser investigative surgical instrumentation includes lasers of argon, carbon dioxide, neodymium-YAG, and ruby, which are used as optical scalpels. Advantages of laser surgical instrumentation include precision, color absorption for lasers in the visible light range, and hemostasis."} {"id": "PMID:1263914", "title": "Management of ruptured abdominal aortic aneurysms.", "content": "If an abdominal aortic aneurysm causes symptoms, surgical replacement is mandatory. Once frank rupture has occurred, the outlook is grave, but immediate surgery and intensive general care can allow survival in up to 50% of patients.", "contents": "Management of ruptured abdominal aortic aneurysms. If an abdominal aortic aneurysm causes symptoms, surgical replacement is mandatory. Once frank rupture has occurred, the outlook is grave, but immediate surgery and intensive general care can allow survival in up to 50% of patients."} {"id": "PMID:1263915", "title": "Nose and throat: occupational hazards.", "content": "Recent reports on the effects of occupational factors in disorders of the nose and throat are reviewed. Chemical irritation is usually responsible for immediate effects, which are transitory but unwelcome. Allergic responses may be more troublesome. The more insidious carcinogenic properties of some industrial irritants are now being recognized.", "contents": "Nose and throat: occupational hazards. Recent reports on the effects of occupational factors in disorders of the nose and throat are reviewed. Chemical irritation is usually responsible for immediate effects, which are transitory but unwelcome. Allergic responses may be more troublesome. The more insidious carcinogenic properties of some industrial irritants are now being recognized."} {"id": "PMID:1263912", "title": "Treatment of intestinal parasites in Australian aboriginal children.", "content": "Five to nine-year-old Aboriginal children on Mitchell River Community maintained a satisfactory growth rate in the presence of multiple infections with intestinal parasites. Intensive treatment was successful in eliminating Giardia lamblia, Entamoeba histolytica, and Strongyloides stercoralis infections, but reinfection with G. lamblia was rapid. Treatment failed to produce any growth spurt in the group. This may have been due to the rapidity of reinfection, but raises the question of whether intestinal parasites contribute significantly to growth retardation or whether growth retarded children have an immune deficit rendering them more susceptible to parasitic infections.", "contents": "Treatment of intestinal parasites in Australian aboriginal children. Five to nine-year-old Aboriginal children on Mitchell River Community maintained a satisfactory growth rate in the presence of multiple infections with intestinal parasites. Intensive treatment was successful in eliminating Giardia lamblia, Entamoeba histolytica, and Strongyloides stercoralis infections, but reinfection with G. lamblia was rapid. Treatment failed to produce any growth spurt in the group. This may have been due to the rapidity of reinfection, but raises the question of whether intestinal parasites contribute significantly to growth retardation or whether growth retarded children have an immune deficit rendering them more susceptible to parasitic infections."} {"id": "PMID:1263913", "title": "Cadmium exposure and renal accumulation in an Australian urban population.", "content": "An indication of the degree of cadmium exposure and renal accumulation in an Australian population (Brisbane) has been obtained from cadmium determinations of urine from 98 patients and post-mortem kidney specimens from 91 patients. Urinary excretion of cadmium from normal or unexposed adults and lead exposed adults was consistent with normal values from other developed countries. There was no apparent relationship between cadmium and lead excretion levels for individual urine specimens. Renal cadmium concentrations were used to estimate the average total cadmium content for a \"standard man\" and renal cortex concentrations. The results were similar to reported studies from the United Kingdom and Europe, but lower than those from Japan. Daily intake of cadmium was estimated to be 30 to 50 mug, which compares favourably with the FAO/WHO1 \"provisional tolerable weekly intake\" of 0-4 to 0-5 mg cadmium per adult per week. It is concluded that Australian populations exposed to potential sources of industrial and environmental cadmium contamination should be investigated.", "contents": "Cadmium exposure and renal accumulation in an Australian urban population. An indication of the degree of cadmium exposure and renal accumulation in an Australian population (Brisbane) has been obtained from cadmium determinations of urine from 98 patients and post-mortem kidney specimens from 91 patients. Urinary excretion of cadmium from normal or unexposed adults and lead exposed adults was consistent with normal values from other developed countries. There was no apparent relationship between cadmium and lead excretion levels for individual urine specimens. Renal cadmium concentrations were used to estimate the average total cadmium content for a \"standard man\" and renal cortex concentrations. The results were similar to reported studies from the United Kingdom and Europe, but lower than those from Japan. Daily intake of cadmium was estimated to be 30 to 50 mug, which compares favourably with the FAO/WHO1 \"provisional tolerable weekly intake\" of 0-4 to 0-5 mg cadmium per adult per week. It is concluded that Australian populations exposed to potential sources of industrial and environmental cadmium contamination should be investigated."} {"id": "PMID:1263932", "title": "Cancer research for small countries: why and how?", "content": "Small countries can, and in fact have a duty, to carry out cancer research. To be effective research must be carried out by teams of no fewer than eight to 10 full-time professional research workers, adequately funded on a relatively long-term basis.", "contents": "Cancer research for small countries: why and how? Small countries can, and in fact have a duty, to carry out cancer research. To be effective research must be carried out by teams of no fewer than eight to 10 full-time professional research workers, adequately funded on a relatively long-term basis."} {"id": "PMID:1263933", "title": "Beclomethasone dipropionate in paediatric asthma.", "content": "An investigation into the use of beclomethasone dipropionate aerosol in the management of 42 severe asthmatic children, ranging in age from two-and-a-half to 16 years with a mean age of seven years is presented.", "contents": "Beclomethasone dipropionate in paediatric asthma. An investigation into the use of beclomethasone dipropionate aerosol in the management of 42 severe asthmatic children, ranging in age from two-and-a-half to 16 years with a mean age of seven years is presented."} {"id": "PMID:1263928", "title": "Histological appraisal of ulcerative colitis fibreoptic colonoscope biopsy specimens.", "content": "The availability of the fibreoptic colonoscope with biopsy facilities has created new opportunities for the investigation of ulcerative colitis. Morphological assessment of the disease, which has hitherto been limited to observing changes in the mucosa of the sigmoid colon and rectum, can now be made on biopsy material obtained under direct vision from the large bowel above the level of the sigmoid. On the basis of 157 colonoscopic biopsies taken from 38 patients with endoscopic appearances of the disease is proposed. The classification is as follows: (i) active chronic phase without ulceration; (ii) active chronic phase with ulceration; (iii) quiescent chronic phase; (iv) healed chronic phase; (v) precancerous phase. Three degrees of severity (mild, moderate and severe) for each phase are recognized.", "contents": "Histological appraisal of ulcerative colitis fibreoptic colonoscope biopsy specimens. The availability of the fibreoptic colonoscope with biopsy facilities has created new opportunities for the investigation of ulcerative colitis. Morphological assessment of the disease, which has hitherto been limited to observing changes in the mucosa of the sigmoid colon and rectum, can now be made on biopsy material obtained under direct vision from the large bowel above the level of the sigmoid. On the basis of 157 colonoscopic biopsies taken from 38 patients with endoscopic appearances of the disease is proposed. The classification is as follows: (i) active chronic phase without ulceration; (ii) active chronic phase with ulceration; (iii) quiescent chronic phase; (iv) healed chronic phase; (v) precancerous phase. Three degrees of severity (mild, moderate and severe) for each phase are recognized."} {"id": "PMID:1263934", "title": "Perforated peptic ulcer long-term follow-up.", "content": "A series of 349 survivors of perforated peptic ulcer was followed for periods of up to 23 years. Almost nine out of every 10 patients suffered from dyspepsia during follow-up. Subsequent elective gastroduodenal surgery was required in more than a quarter of the cases. The surgery rate for gastric ulcer was more than one and a half times that for pyloroduodenal ulcer, and for females almost double that for males. The highest rate of all was for females with gastric ulcer, of whom almost one half came for surgery. One in five patients bled during follow-up. One in eight developed stenosis of the stomach of duodenum, and one in 11 perforated again. There was a significantly increased incidence of subsequent perforation and stenosis in those with an initial perforation of 5 mm or more in diameter. Gastric carcinoma occurred in less than 2% of cases and was restricted to cases of pyloroduodenal perforation. When complications occurred, the majority did so within five years. Only 15% of the 262 patients about whom complete information was available had no complications on follow-up. The indications for definitive surgery at perforation should be extended to include perforated gastric ulcer in the female, particularly if the ulcer is large.", "contents": "Perforated peptic ulcer long-term follow-up. A series of 349 survivors of perforated peptic ulcer was followed for periods of up to 23 years. Almost nine out of every 10 patients suffered from dyspepsia during follow-up. Subsequent elective gastroduodenal surgery was required in more than a quarter of the cases. The surgery rate for gastric ulcer was more than one and a half times that for pyloroduodenal ulcer, and for females almost double that for males. The highest rate of all was for females with gastric ulcer, of whom almost one half came for surgery. One in five patients bled during follow-up. One in eight developed stenosis of the stomach of duodenum, and one in 11 perforated again. There was a significantly increased incidence of subsequent perforation and stenosis in those with an initial perforation of 5 mm or more in diameter. Gastric carcinoma occurred in less than 2% of cases and was restricted to cases of pyloroduodenal perforation. When complications occurred, the majority did so within five years. Only 15% of the 262 patients about whom complete information was available had no complications on follow-up. The indications for definitive surgery at perforation should be extended to include perforated gastric ulcer in the female, particularly if the ulcer is large."} {"id": "PMID:1263935", "title": "Vitamin B12 malabsorption associated with a normal Schilling test result.", "content": "A patient with vitamin B12 deficiency and a true normal Schilling test result is presented. This patient could absorb chemically pure vitamin B12 normally but could not absorb protein-bound vitamin B12.", "contents": "Vitamin B12 malabsorption associated with a normal Schilling test result. A patient with vitamin B12 deficiency and a true normal Schilling test result is presented. This patient could absorb chemically pure vitamin B12 normally but could not absorb protein-bound vitamin B12."} {"id": "PMID:1263936", "title": "Management of asymptomatic abdominal aortic aneurysms.", "content": "The decision whether to operate on a patient with an asymptomatic abdominal aortic aneurysm is difficult. It depends on balancing the risk of its future rupture against the risk of the operation. A large aneurysm (greater than 7 cm in diameter) should certainly be replaced. A small aneurysm (less than 5 cm across) should simply be observed. The need for surgery on an aneurysm between 5 cm and 7 cm in diameter is doubtful.", "contents": "Management of asymptomatic abdominal aortic aneurysms. The decision whether to operate on a patient with an asymptomatic abdominal aortic aneurysm is difficult. It depends on balancing the risk of its future rupture against the risk of the operation. A large aneurysm (greater than 7 cm in diameter) should certainly be replaced. A small aneurysm (less than 5 cm across) should simply be observed. The need for surgery on an aneurysm between 5 cm and 7 cm in diameter is doubtful."} {"id": "PMID:1263927", "title": "Gastrointestinal endoscopic polypectomy.", "content": "Recent advances in the field of gastroenterological endoscopy have now embraced endoscopic polypectomy. Experiences at the Royal North Shore Hospital over a period of one year include 42 colonic and three gastric polypectomies. Rectal bleeding was the main presenting feature in the patients with colonic polyps. All colonic polyps were situated between the sigmoid and transverse colon. Eighteen polyps were under 1 cm in size, 15 between 1 and 2 cm and nine over 2 cm. There was one carcinoma detected in each of these groups. No significant complications were encountered with any of these patients. The high yield of malignancy, none of which could be suspected on clinical or radiological grounds, more than justifies the introduction of this endoscopic procedure which will offer considerable saving from both the point of view of economic factors and personal discomfort.", "contents": "Gastrointestinal endoscopic polypectomy. Recent advances in the field of gastroenterological endoscopy have now embraced endoscopic polypectomy. Experiences at the Royal North Shore Hospital over a period of one year include 42 colonic and three gastric polypectomies. Rectal bleeding was the main presenting feature in the patients with colonic polyps. All colonic polyps were situated between the sigmoid and transverse colon. Eighteen polyps were under 1 cm in size, 15 between 1 and 2 cm and nine over 2 cm. There was one carcinoma detected in each of these groups. No significant complications were encountered with any of these patients. The high yield of malignancy, none of which could be suspected on clinical or radiological grounds, more than justifies the introduction of this endoscopic procedure which will offer considerable saving from both the point of view of economic factors and personal discomfort."} {"id": "PMID:1263938", "title": "What does the intern do?", "content": "A minute-by minute professional work study was undertaken on three interns at the Royal Adelaide Hospital from Monday to Friday of three consecutive working weeks in December, 1972. The clinics studied were general medical, general surgical and urological. There are obvious major limitations in extrapolating the results of this study beyong the hospital involved at the time of year concerned. Nevertheless, allowing for this factor, it is probably a matter of general principle that there is excessive disproportion between the time spent by an intern in clinical work, contrasted with the time spent in clinical activity, transit, and waiting time. It is suggested that the work of an intern needs more support by better secretarial and similar facilities.", "contents": "What does the intern do? A minute-by minute professional work study was undertaken on three interns at the Royal Adelaide Hospital from Monday to Friday of three consecutive working weeks in December, 1972. The clinics studied were general medical, general surgical and urological. There are obvious major limitations in extrapolating the results of this study beyong the hospital involved at the time of year concerned. Nevertheless, allowing for this factor, it is probably a matter of general principle that there is excessive disproportion between the time spent by an intern in clinical work, contrasted with the time spent in clinical activity, transit, and waiting time. It is suggested that the work of an intern needs more support by better secretarial and similar facilities."} {"id": "PMID:1263948", "title": "The paediatric surgeon-operating physician or surgeon.", "content": "To elucidate a child's symptoms one must understand the child. A wide range of medical conditions may present to the consultant paediatric surgeon, so that he must be qualified by training to recognize them. Within a children's hospital he is aptly trained and placed to act as a focal point whenever disease or injury involves a number of surgical specialties.", "contents": "The paediatric surgeon-operating physician or surgeon. To elucidate a child's symptoms one must understand the child. A wide range of medical conditions may present to the consultant paediatric surgeon, so that he must be qualified by training to recognize them. Within a children's hospital he is aptly trained and placed to act as a focal point whenever disease or injury involves a number of surgical specialties."} {"id": "PMID:1263949", "title": "Rotaviruses and acute gastroenteritis of infants and children.", "content": "By means of electron microscopy and ultracentrifugation techniques rotavirus-like particles have been found in 84 of 269 specimens of faeces collected from infants and young children admitted to the Royal Alexandra Hospital for Children, Camperdown, N.S.W. during the usual winter outbreak of infantile gastroenteritis. Morphologically intact viruses were also found in faecal specimens stored at -20 degrees C for up to nine years. Rotaviruses were found in specimens collected from five newborn infants with diarrhoea, and in a subsequent survey of the nursery when 23 neonates without diarrhoea were present, 12 (52 %) were found to be excreting virus. Morphologically similar viruses were found in six of 16 faecal specimens from newborn calves with gastroenteritis (scours), and an antigenic relationship between the rotaviruses of human and bovine origin has been demonstrated.", "contents": "Rotaviruses and acute gastroenteritis of infants and children. By means of electron microscopy and ultracentrifugation techniques rotavirus-like particles have been found in 84 of 269 specimens of faeces collected from infants and young children admitted to the Royal Alexandra Hospital for Children, Camperdown, N.S.W. during the usual winter outbreak of infantile gastroenteritis. Morphologically intact viruses were also found in faecal specimens stored at -20 degrees C for up to nine years. Rotaviruses were found in specimens collected from five newborn infants with diarrhoea, and in a subsequent survey of the nursery when 23 neonates without diarrhoea were present, 12 (52 %) were found to be excreting virus. Morphologically similar viruses were found in six of 16 faecal specimens from newborn calves with gastroenteritis (scours), and an antigenic relationship between the rotaviruses of human and bovine origin has been demonstrated."} {"id": "PMID:1263950", "title": "New virus associated with diarrhoea in neonates.", "content": "Since December, 1974, there has been an increase in the incidence of acute diarrhoea in the neonatal nurseries of five Melbourne metropolitan hospitals. Four of these have had epidemics, and the incidence of endemic diarrhoeal disease has increased. Extracts of faeces from 148 patients from the five hospitals were examined by electron microscopy. \"Duovirus\" particles were detected in 82 of these extracts, including at least one from each hospital. No bacterial pathogens were isolated. It seems likely that \"duovirus\" is an important cause of sporadic and epidemic acute diarrhoeal disease in neonates. It is important to note that the absence of a recognized bacterial pathogen does not exclude an infective cause, especially when sugar intolerance is present. Appropriate measures to minimize the spread of infection must be employed.", "contents": "New virus associated with diarrhoea in neonates. Since December, 1974, there has been an increase in the incidence of acute diarrhoea in the neonatal nurseries of five Melbourne metropolitan hospitals. Four of these have had epidemics, and the incidence of endemic diarrhoeal disease has increased. Extracts of faeces from 148 patients from the five hospitals were examined by electron microscopy. \"Duovirus\" particles were detected in 82 of these extracts, including at least one from each hospital. No bacterial pathogens were isolated. It seems likely that \"duovirus\" is an important cause of sporadic and epidemic acute diarrhoeal disease in neonates. It is important to note that the absence of a recognized bacterial pathogen does not exclude an infective cause, especially when sugar intolerance is present. Appropriate measures to minimize the spread of infection must be employed."} {"id": "PMID:1263957", "title": "Triage in civilian practice.", "content": "A triage area for the assessment and treatment of acutely ill patients on their admission to hospital was created. Four groups of patients were defined who were to be sent to this area rather than be treated in the casualty department. The area was contiguous with the hospital intensive care unit rather than the casualty department as the ease of providing trained staff members and equipment on a 24-hour basis outweighed the disadvantage of geographical separation from the casualty department. The increase in workload created for the intensive care members of staff was small, while the reduction in delay for seriously ill patients was considerable.", "contents": "Triage in civilian practice. A triage area for the assessment and treatment of acutely ill patients on their admission to hospital was created. Four groups of patients were defined who were to be sent to this area rather than be treated in the casualty department. The area was contiguous with the hospital intensive care unit rather than the casualty department as the ease of providing trained staff members and equipment on a 24-hour basis outweighed the disadvantage of geographical separation from the casualty department. The increase in workload created for the intensive care members of staff was small, while the reduction in delay for seriously ill patients was considerable."} {"id": "PMID:1263960", "title": "Accuracy of blood glucose measurements using a reflectance meter.", "content": "The performance of a stock reflectance meter for measuring blood glucose levels with glucose oxidase test strips has been assessed. Glucose values obtained were spuriously high, and the response of the instrument was non-linear. The instrument could not be recommended as an accurate means of determining glucose levels, but may be useful for detecting hyperglycaemia and hypoglycaemia.", "contents": "Accuracy of blood glucose measurements using a reflectance meter. The performance of a stock reflectance meter for measuring blood glucose levels with glucose oxidase test strips has been assessed. Glucose values obtained were spuriously high, and the response of the instrument was non-linear. The instrument could not be recommended as an accurate means of determining glucose levels, but may be useful for detecting hyperglycaemia and hypoglycaemia."} {"id": "PMID:1263968", "title": "Reuse of a disposable dialyser for home dialysis.", "content": "A disposable parallel flow plate dialyser (Gambro Lundia) has been evaluated. It is comparable in surface area and efficiency to the standard Kiil dialyser and can be regularly reused six times, combining the reliability and convenience of a prefabricated, factory-tested unit with the low cost of the Kiil dialyser.", "contents": "Reuse of a disposable dialyser for home dialysis. A disposable parallel flow plate dialyser (Gambro Lundia) has been evaluated. It is comparable in surface area and efficiency to the standard Kiil dialyser and can be regularly reused six times, combining the reliability and convenience of a prefabricated, factory-tested unit with the low cost of the Kiil dialyser."} {"id": "PMID:1263969", "title": "Cerebellitis in glandular fever.", "content": "Cerebellitis as an unusual manifestation of infectious mononucleosis is reported for the first time in Australia. Complete recovery occurred, as has been the rule in previously described cases. The difficulty that may be encountered in early diagnosis is discussed, and screening for infectious mononucleosis is suggested for elusive neurological illnesses. The possible significance of cerebrospinal fluid antibodies is considered.", "contents": "Cerebellitis in glandular fever. Cerebellitis as an unusual manifestation of infectious mononucleosis is reported for the first time in Australia. Complete recovery occurred, as has been the rule in previously described cases. The difficulty that may be encountered in early diagnosis is discussed, and screening for infectious mononucleosis is suggested for elusive neurological illnesses. The possible significance of cerebrospinal fluid antibodies is considered."} {"id": "PMID:1263970", "title": "Treatment with the artificial kidney (dialysis).", "content": "For patients with chronic renal disease, haemodialysis can provide reasonable rehabilitation and, in most cases, a life expectancy in excess of 10 years. However, dialysis is unable to provide for any loss of the kidneys' endocrine or metabolic activities and the kidneys' excretory capacity is only replaced suboptimally. Recent well controlled studies on the frequency, time and techniques of dialysis, instigated mostly as a consequence of recent hypotheses, such as the \"middle molecule\" theory and consideration of the potential importance of residual renal function, have resulted in a complete reassessment of the nature of adequate dialysis. Developments such as sorbent-based dialysis are leading to a wearable dialyser. Theoretical and hardware developments are providing not only more adequate treatment, but improved rehabilitation for those patients on chronic dialysis therapy.", "contents": "Treatment with the artificial kidney (dialysis). For patients with chronic renal disease, haemodialysis can provide reasonable rehabilitation and, in most cases, a life expectancy in excess of 10 years. However, dialysis is unable to provide for any loss of the kidneys' endocrine or metabolic activities and the kidneys' excretory capacity is only replaced suboptimally. Recent well controlled studies on the frequency, time and techniques of dialysis, instigated mostly as a consequence of recent hypotheses, such as the \"middle molecule\" theory and consideration of the potential importance of residual renal function, have resulted in a complete reassessment of the nature of adequate dialysis. Developments such as sorbent-based dialysis are leading to a wearable dialyser. Theoretical and hardware developments are providing not only more adequate treatment, but improved rehabilitation for those patients on chronic dialysis therapy."} {"id": "PMID:1263972", "title": "The heart attack and doctor/patient communication.", "content": "In patients with recent proven or suspected myocardial infarction, understanding of the nature of a heart attack was explored. A wide range of misconceptions, some of them frightening, was revealed; there was a poor understanding of some terms commonly used in discussion with patients; the potential for creation of new misconceptions by doctors and nurses was highlighted.", "contents": "The heart attack and doctor/patient communication. In patients with recent proven or suspected myocardial infarction, understanding of the nature of a heart attack was explored. A wide range of misconceptions, some of them frightening, was revealed; there was a poor understanding of some terms commonly used in discussion with patients; the potential for creation of new misconceptions by doctors and nurses was highlighted."} {"id": "PMID:1263979", "title": "Post-pill anovulation.", "content": "Basal temperature records were maintained by 346 women after ceasing to take oral contraceptives; 167 had ceased using combined and 179 had ceased using low-dose sequential formulations. In the first cycle after withdrawal of low-dose sequential pills, 11 (6%) women failed to ovulate and ovulation was delayed in five cases. Short luteal cycles occurred in 14 subjects. In 83% of the subjects there was no disturbance of ovulation. In the first cycle after withdrawal of combined oral contraceptives, 49 (30%) women failed to ovulate and ovulation was delayed in 29 cases. A short luteal phase was observed in 26 subjects. In only 38% of the subjects was there no disturbance of ovulation. The minimal disturbance to ovulation in the cycle after the withdrawal of low-dose sequential formulation indicates that this type of oral contraceptive carries little risk of producing post-pill infertility. Women under the age of 21 years were anovulatory nearly twice as frequently as older women after ceasing to use combined oral contraceptives.", "contents": "Post-pill anovulation. Basal temperature records were maintained by 346 women after ceasing to take oral contraceptives; 167 had ceased using combined and 179 had ceased using low-dose sequential formulations. In the first cycle after withdrawal of low-dose sequential pills, 11 (6%) women failed to ovulate and ovulation was delayed in five cases. Short luteal cycles occurred in 14 subjects. In 83% of the subjects there was no disturbance of ovulation. In the first cycle after withdrawal of combined oral contraceptives, 49 (30%) women failed to ovulate and ovulation was delayed in 29 cases. A short luteal phase was observed in 26 subjects. In only 38% of the subjects was there no disturbance of ovulation. The minimal disturbance to ovulation in the cycle after the withdrawal of low-dose sequential formulation indicates that this type of oral contraceptive carries little risk of producing post-pill infertility. Women under the age of 21 years were anovulatory nearly twice as frequently as older women after ceasing to use combined oral contraceptives."} {"id": "PMID:1263980", "title": "Post-pill infertility.", "content": "One hundred and fifty-one nulligravid women and 63 parous women stopped taking low-dose sequential oral contraceptives in order to become pregnant. During the first post-Pill cycle, 39% of the nulligravid and 54% of the parous women conceived. These figures have been compared with data from the Royal College of General Practitioners survey in England, in which 13% of nulligravid and 17% of parous women conceived in the first cycle after ceasing to take combined oral contraceptives. The percentage of nulligravid women not pregnant six months after withdrawal of low-dose sequential formulations was 19% compared with 32% after withdrawal of combined oral contraceptives. The corresponding figures for parous women were 5% and 21%. Available data suggest that after withdrawal of low-dose sequential oral contraceptives, the incidence of post-Pill infertility is lower than that after withdrawal of combined oral contraceptives. The extent of this difference is 16% three months after withdrawal of the Pill and 10% six months after attempting pregnancy.", "contents": "Post-pill infertility. One hundred and fifty-one nulligravid women and 63 parous women stopped taking low-dose sequential oral contraceptives in order to become pregnant. During the first post-Pill cycle, 39% of the nulligravid and 54% of the parous women conceived. These figures have been compared with data from the Royal College of General Practitioners survey in England, in which 13% of nulligravid and 17% of parous women conceived in the first cycle after ceasing to take combined oral contraceptives. The percentage of nulligravid women not pregnant six months after withdrawal of low-dose sequential formulations was 19% compared with 32% after withdrawal of combined oral contraceptives. The corresponding figures for parous women were 5% and 21%. Available data suggest that after withdrawal of low-dose sequential oral contraceptives, the incidence of post-Pill infertility is lower than that after withdrawal of combined oral contraceptives. The extent of this difference is 16% three months after withdrawal of the Pill and 10% six months after attempting pregnancy."} {"id": "PMID:1263981", "title": "Cerebral tumour with intracranial angioma.", "content": "This paper concerns the simultaneous occurrence of tumours, a meningioma and intracranial angioma, of diverse histological characteristics. Their clinical radiological and pathological implications are discussed.", "contents": "Cerebral tumour with intracranial angioma. This paper concerns the simultaneous occurrence of tumours, a meningioma and intracranial angioma, of diverse histological characteristics. Their clinical radiological and pathological implications are discussed."} {"id": "PMID:1263984", "title": "Facial and cervical injuries.", "content": "It is not commonly appreciated that mandibular and maxillary fractures are occasionally associated with fractures of cervical vertebrae. An incidence of 1-6% in a three-year survey at the Royal Brisbane Hospital is reported and the implications are discussed.", "contents": "Facial and cervical injuries. It is not commonly appreciated that mandibular and maxillary fractures are occasionally associated with fractures of cervical vertebrae. An incidence of 1-6% in a three-year survey at the Royal Brisbane Hospital is reported and the implications are discussed."} {"id": "PMID:1263989", "title": "[The normal range of the pulmonary artery pressure during ergometrical exercise (author's transl)].", "content": "In healthy subjects the pulmonary artery pressure was measured during exercise tests with the aid of the flow guided catheterisation. The work load was determined on bicycle ergometer in recumbent position in form of a multistage exercise test with relative steady state periods till exhaustion was reached. In this way, during the highest work load (200 Watt) the systolic pulmonary artery pressure was 33.9 +/- 5.5 mm Hg, the diastolic pressure 17.5 +/- 3.6 mm Hg and the pulmonary mean pressure 24.7 +/- 4.0 mm Hg. The factors influencing the pulmonary artery pressure during work are discussed.", "contents": "[The normal range of the pulmonary artery pressure during ergometrical exercise (author's transl)]. In healthy subjects the pulmonary artery pressure was measured during exercise tests with the aid of the flow guided catheterisation. The work load was determined on bicycle ergometer in recumbent position in form of a multistage exercise test with relative steady state periods till exhaustion was reached. In this way, during the highest work load (200 Watt) the systolic pulmonary artery pressure was 33.9 +/- 5.5 mm Hg, the diastolic pressure 17.5 +/- 3.6 mm Hg and the pulmonary mean pressure 24.7 +/- 4.0 mm Hg. The factors influencing the pulmonary artery pressure during work are discussed."} {"id": "PMID:1263990", "title": "[Diagnostic application of external electrical impulses in form of an overdrive for the influence of an implanted QRS inhibited demand pacemaker system (author's transl)].", "content": "The possibility of influencing an implanted demand pacemaker system by means of an external electrical impulse has already been described by several authors. In this paper further clinical applications of this method are discussed in relationship to patients who have a pacemaker of the QRS inhibited type. Electrodes are applied externally over the regions of the pacemaker generator and the catheter tip. Electrical impulses are then given at a higher frequency than those of the implanted pacemaker, thus enabling the impulses of the internal pacemaker to be inhibited, and consequently the spontaneous action of the heart to be observed. Further possible clinical applications with the aid of examples are discussed: the identification of persistent arrhythmias, digitalis intoxication, fresh cardiac ischaemias, as well as evidence of the need for temporary stimulation during generator change.", "contents": "[Diagnostic application of external electrical impulses in form of an overdrive for the influence of an implanted QRS inhibited demand pacemaker system (author's transl)]. The possibility of influencing an implanted demand pacemaker system by means of an external electrical impulse has already been described by several authors. In this paper further clinical applications of this method are discussed in relationship to patients who have a pacemaker of the QRS inhibited type. Electrodes are applied externally over the regions of the pacemaker generator and the catheter tip. Electrical impulses are then given at a higher frequency than those of the implanted pacemaker, thus enabling the impulses of the internal pacemaker to be inhibited, and consequently the spontaneous action of the heart to be observed. Further possible clinical applications with the aid of examples are discussed: the identification of persistent arrhythmias, digitalis intoxication, fresh cardiac ischaemias, as well as evidence of the need for temporary stimulation during generator change."} {"id": "PMID:1263994", "title": "[Acute myoglobinuria accompanied by renal failure in high febril infection (author's transl)].", "content": "A 41 year old man developed a myolysis with myoglobinuria during a period of high fever. The clinical signs were severe myalgia with general muscular weakness without manifest localized paresis. Electromyographically a diffuse generalized floride myopathy was found. Besides the extreme increase of CPK, a myoglobinuria was already macroscopically visible, which caused an acute renal failure. The treatment included corticosteroids and hemodialysis. An illness of several weaks was followed by complete recovery. As other known factors leading to myoglobinuria have been excluded, and the complement fixation reaction for Herpes simplex was more than 1:80, a viral-toxic etiology of this disease might be considered.", "contents": "[Acute myoglobinuria accompanied by renal failure in high febril infection (author's transl)]. A 41 year old man developed a myolysis with myoglobinuria during a period of high fever. The clinical signs were severe myalgia with general muscular weakness without manifest localized paresis. Electromyographically a diffuse generalized floride myopathy was found. Besides the extreme increase of CPK, a myoglobinuria was already macroscopically visible, which caused an acute renal failure. The treatment included corticosteroids and hemodialysis. An illness of several weaks was followed by complete recovery. As other known factors leading to myoglobinuria have been excluded, and the complement fixation reaction for Herpes simplex was more than 1:80, a viral-toxic etiology of this disease might be considered."} {"id": "PMID:1263995", "title": "[Treatment of peripheral occlusive vascular disease with pentoxifylin (author's transl)].", "content": "102 patients suffering from peripheral occlusive vascular disease were treated with Pentoxifylline (Trental) parenterally (i.v. infusions) and orally (dragees). Surprisingly good therapeutic response was obtained not only in patients stage II but also stage III (after Fontaine), in total 84% of the patients showing improvement. These favourable results can only be explained by increase of nutritious circulation indicating an improvement of blood-flow-properties in the microvasculature. The observed particular efficacy of Pentoxifylline necessitates a more differentiated valuation of the systemic (intravenous) administration of vasoactive drugs all the more so as the majority of patients with occlusive vascular disease are accessible to conservative treatment only.", "contents": "[Treatment of peripheral occlusive vascular disease with pentoxifylin (author's transl)]. 102 patients suffering from peripheral occlusive vascular disease were treated with Pentoxifylline (Trental) parenterally (i.v. infusions) and orally (dragees). Surprisingly good therapeutic response was obtained not only in patients stage II but also stage III (after Fontaine), in total 84% of the patients showing improvement. These favourable results can only be explained by increase of nutritious circulation indicating an improvement of blood-flow-properties in the microvasculature. The observed particular efficacy of Pentoxifylline necessitates a more differentiated valuation of the systemic (intravenous) administration of vasoactive drugs all the more so as the majority of patients with occlusive vascular disease are accessible to conservative treatment only."} {"id": "PMID:1263996", "title": "[Anabolic steroids: damages, effect on performance, and on metabolism (author's transl)].", "content": "10 normal persons (age: x=22 years) and 15 weight lifters (age: x=27 years) were studied before and three months after taking Nandrolone danoate (ND). Strength exercises, hear rate during ergometer work, physical working capacity and certain biochemical variables were measured in the experimental group, as well as in a controll group of 7 weight lifters. Six weight lifters in the experimental group who had been taking ND for at least 3 years were also studied to determine whether there were any deleterious effects on their health. In addition, 75 athletes who had been taking anabolic steroids were investigated to determine the possible effects. It was found that: 1. In spite of an 7% increase in performance, the maximal heart rate was not higher when the subjects took ND. During submaximal work loads the heart rate (p less than 0.025) and the blood lactate level (p less than 0.05) were lower. During physical work, there was essentially no effect of ND on glucose or total lipids in serum. 2. The results from the three-months study, from the weight lifters taking ND for 3 years, as well as from 26 of the 57 athletes who had been taking ND showed no evidence of a deleterious effect of ND (based on 26 biochemical measurements). It would appear, therefore, that the general suggestion of a detrimental effect of anabolic hormones is not justified. 3. Damages or functional disturbances were found in 31 athletes and 3 weight lifters of the experimental group after oral application of anabolic alkyl-steroids. After a period of time without alkyl-steroid administration, all investigated biochemical parameters returned to normal levels; thus it appears that the aforementioned pathological findings are reversible changes in liver function.", "contents": "[Anabolic steroids: damages, effect on performance, and on metabolism (author's transl)]. 10 normal persons (age: x=22 years) and 15 weight lifters (age: x=27 years) were studied before and three months after taking Nandrolone danoate (ND). Strength exercises, hear rate during ergometer work, physical working capacity and certain biochemical variables were measured in the experimental group, as well as in a controll group of 7 weight lifters. Six weight lifters in the experimental group who had been taking ND for at least 3 years were also studied to determine whether there were any deleterious effects on their health. In addition, 75 athletes who had been taking anabolic steroids were investigated to determine the possible effects. It was found that: 1. In spite of an 7% increase in performance, the maximal heart rate was not higher when the subjects took ND. During submaximal work loads the heart rate (p less than 0.025) and the blood lactate level (p less than 0.05) were lower. During physical work, there was essentially no effect of ND on glucose or total lipids in serum. 2. The results from the three-months study, from the weight lifters taking ND for 3 years, as well as from 26 of the 57 athletes who had been taking ND showed no evidence of a deleterious effect of ND (based on 26 biochemical measurements). It would appear, therefore, that the general suggestion of a detrimental effect of anabolic hormones is not justified. 3. Damages or functional disturbances were found in 31 athletes and 3 weight lifters of the experimental group after oral application of anabolic alkyl-steroids. After a period of time without alkyl-steroid administration, all investigated biochemical parameters returned to normal levels; thus it appears that the aforementioned pathological findings are reversible changes in liver function."} {"id": "PMID:1263997", "title": "[Embolia cutis medicamentosa (author's transl)].", "content": "A rare secondary effect of intramuscular injections is reported in three own observations: This embolia cutis medicamentosa has been relatively often found in former times as result of bismuthe and mercury injections during lues therapy and today is only occasionally found, especially after intramuscular injections of phenylbutazone-containing antirheumatics. The question is discussed whether this medicamental embolism is really due to an embolic occlusion of small skin arteries. The typical clinical picture of the infarct-resembling skin necrosis in livid skin area could also be explained by vessel necrosis or thrombosis in the site of injection itself.", "contents": "[Embolia cutis medicamentosa (author's transl)]. A rare secondary effect of intramuscular injections is reported in three own observations: This embolia cutis medicamentosa has been relatively often found in former times as result of bismuthe and mercury injections during lues therapy and today is only occasionally found, especially after intramuscular injections of phenylbutazone-containing antirheumatics. The question is discussed whether this medicamental embolism is really due to an embolic occlusion of small skin arteries. The typical clinical picture of the infarct-resembling skin necrosis in livid skin area could also be explained by vessel necrosis or thrombosis in the site of injection itself."} {"id": "PMID:1263998", "title": "[Tricyclic psychotropic drugs: complications and therapy of Choloprothixen-intoxication (author's transl)].", "content": "The broad use of tricyclic psychotropic drugs demands from the physician to take in account the side effects of these drugs. These side effects relate primarily to the cardiovascular system. We describe a suicidal Chlorprothixen(Taractan-)intoxication of a 27 year old female patient. The progress of this intoxication was characterized by severe arrhythmias, mainly ventricular tachycardias. The pathogeneisis of the cardiotoxic reaction is discussed. Since there is no specific antidot against these drugs, therapy of side effects is limited to symptomatic treatment including administration of cholinergic drugs. Severe cardiovascular reaction also can be found, when the drugs are used in therapeutic doses. The cardiodepressive effect of tricyclic psychotropic drugs may lead to considerable complications, especially in older patients.", "contents": "[Tricyclic psychotropic drugs: complications and therapy of Choloprothixen-intoxication (author's transl)]. The broad use of tricyclic psychotropic drugs demands from the physician to take in account the side effects of these drugs. These side effects relate primarily to the cardiovascular system. We describe a suicidal Chlorprothixen(Taractan-)intoxication of a 27 year old female patient. The progress of this intoxication was characterized by severe arrhythmias, mainly ventricular tachycardias. The pathogeneisis of the cardiotoxic reaction is discussed. Since there is no specific antidot against these drugs, therapy of side effects is limited to symptomatic treatment including administration of cholinergic drugs. Severe cardiovascular reaction also can be found, when the drugs are used in therapeutic doses. The cardiodepressive effect of tricyclic psychotropic drugs may lead to considerable complications, especially in older patients."} {"id": "PMID:1264001", "title": "[Complications of the sternal puncture (author's transl)].", "content": "The case of a 57 year old female patient suffering from plasmocytoma with a sternal fracture after local puncture characterized by a late healing tendency is reported. According to the literature the complications of this diagnostic method, known up to now, are described with special emphasis to the pathomechanism and the clinical course of the mostly fatal sternal perforation with cardiac tamponade. Puncture of the iliac crest instead of the sternal region is recommended in cases with serious osteoporotic or osteolytic defects of the sternal bone.", "contents": "[Complications of the sternal puncture (author's transl)]. The case of a 57 year old female patient suffering from plasmocytoma with a sternal fracture after local puncture characterized by a late healing tendency is reported. According to the literature the complications of this diagnostic method, known up to now, are described with special emphasis to the pathomechanism and the clinical course of the mostly fatal sternal perforation with cardiac tamponade. Puncture of the iliac crest instead of the sternal region is recommended in cases with serious osteoporotic or osteolytic defects of the sternal bone."} {"id": "PMID:1264004", "title": "[Telemetry of blood pressure in healthy subjects and patients with tachycardia and hypertension under Prindolol treatment].", "content": "The effect of 0.4 mg i.v. Prindolol on arterial blood pressure and heart rate was investigated with continuous measurement by telemetry. The 19 healthy subjects and 13 patients were controlled at rest supine, standing and finally during exercise. Following Prindolol a significant decrease of blood pressure and heart rate was observed, in particular in the group suffering from hypertension and tachycardia and under conditions of exercise, when compared with the pretreatment values. No side effects were noted.", "contents": "[Telemetry of blood pressure in healthy subjects and patients with tachycardia and hypertension under Prindolol treatment]. The effect of 0.4 mg i.v. Prindolol on arterial blood pressure and heart rate was investigated with continuous measurement by telemetry. The 19 healthy subjects and 13 patients were controlled at rest supine, standing and finally during exercise. Following Prindolol a significant decrease of blood pressure and heart rate was observed, in particular in the group suffering from hypertension and tachycardia and under conditions of exercise, when compared with the pretreatment values. No side effects were noted."} {"id": "PMID:1264003", "title": "[Early mobilization after myocardial infarction. Hemodynamic and metabolic studies].", "content": "In a controlled study two groups of patients with acute myocardial infarction were compared. One group consisted of 75 patients who were early mobilized; a control group of 38 patients was treated conservatively. Although the early mobilized patients showed a slightly increased stress on the hemodynamics these findings had no clinical significance: the complication rate in this group was not higher than in the conservatively treated patients. The main advantage of early mobilization however as compared to conservative treatment seems to be the prognostically and psychologically favourable effect especially with respect to rehabilitation.", "contents": "[Early mobilization after myocardial infarction. Hemodynamic and metabolic studies]. In a controlled study two groups of patients with acute myocardial infarction were compared. One group consisted of 75 patients who were early mobilized; a control group of 38 patients was treated conservatively. Although the early mobilized patients showed a slightly increased stress on the hemodynamics these findings had no clinical significance: the complication rate in this group was not higher than in the conservatively treated patients. The main advantage of early mobilization however as compared to conservative treatment seems to be the prognostically and psychologically favourable effect especially with respect to rehabilitation."} {"id": "PMID:1264007", "title": "[Appearance of anaerobic vibrionen species (vibriones) in cases of chronically recurrent vaginal fluor (author's transl)].", "content": "In 480 patients suffering from chronically recurring and/or therapy-resistant fluor of the outer female urogenital tract, a vaginal virbiosis was stated in 54 cases as cause of the fluor complaints lasting, for the most part, longer than five years. Aspects of vaginal vibriosis and respective therapy are discussed.", "contents": "[Appearance of anaerobic vibrionen species (vibriones) in cases of chronically recurrent vaginal fluor (author's transl)]. In 480 patients suffering from chronically recurring and/or therapy-resistant fluor of the outer female urogenital tract, a vaginal virbiosis was stated in 54 cases as cause of the fluor complaints lasting, for the most part, longer than five years. Aspects of vaginal vibriosis and respective therapy are discussed."} {"id": "PMID:1264008", "title": "[Severe course of an infection with Leptospira grippotyphosa (author's transl)].", "content": "In a 22 years old female patient severe jaundice, renal failure and myocarditis developed 3 days after the onset of fever and other uncharacteristic symptoms. In dark-field microscopy leptospires were found. Inspite of high-dose penicillin therapy exitus letalis occurred in myocardial and circulatory failure, due to a severe interstitial myocarditis. Leptospira grippotyphosa could be proven serologically as the causative bacterium. It is pointed out, that leptospirosis inspite of their rare occurrence should be included in the differential diagnosis of infections of undetermined origin, especially if jaundice develops. The demonstration of leptospira in blood, cerebro-spinal fluid or urin by means of darkfield microscopy may quickly support the diagnosis. Since the course of severe leptospirosis can be influenced significantly only up to the 4th day after the onset, high-dose penicillin G or tetracycline therapy should be initiated already when the clinical suspicion is present.", "contents": "[Severe course of an infection with Leptospira grippotyphosa (author's transl)]. In a 22 years old female patient severe jaundice, renal failure and myocarditis developed 3 days after the onset of fever and other uncharacteristic symptoms. In dark-field microscopy leptospires were found. Inspite of high-dose penicillin therapy exitus letalis occurred in myocardial and circulatory failure, due to a severe interstitial myocarditis. Leptospira grippotyphosa could be proven serologically as the causative bacterium. It is pointed out, that leptospirosis inspite of their rare occurrence should be included in the differential diagnosis of infections of undetermined origin, especially if jaundice develops. The demonstration of leptospira in blood, cerebro-spinal fluid or urin by means of darkfield microscopy may quickly support the diagnosis. Since the course of severe leptospirosis can be influenced significantly only up to the 4th day after the onset, high-dose penicillin G or tetracycline therapy should be initiated already when the clinical suspicion is present."} {"id": "PMID:1264009", "title": "[Clotrimazol in the treatment of candida infections in premature and newborn children (author's transl)].", "content": "The early infancy is especially affected by moniliasis in pediatrics. The causes are: broad spread of Candida albicans in the environment of these children, a growing immunity, the immaturity of the skin and an insufficient candida-static activity of the serum. The prematures and the newborns with an irregular birth are especially endangered. This danger is increased by simultaneous antibiotic therapy. The arising mycosis can reach from the relative harmless mouth- and diaper-thrush to serious septic diseases. An effective therapy therefore is very much desired. As new efficacious medicaments the derivates of imidazol, Clotrimazol, have proved satisfactory for the treatment of mycoses. It is as Canesten marketed. The drug possesses a strong activity against numerous fungi, some protozoa, and bacteria. In this paper it is reported on own pharmacokinetic and therapeutic investigations with Clotrimazol. The substance has been very useful for the treatment of mouth- and diaper-thrush. Clotrimazol was administered as BAYb 5097 peroral and local as Canesten -solution 1% and -cream 1%. There were 171 treatments carried out. Essential side-effects were not observed.", "contents": "[Clotrimazol in the treatment of candida infections in premature and newborn children (author's transl)]. The early infancy is especially affected by moniliasis in pediatrics. The causes are: broad spread of Candida albicans in the environment of these children, a growing immunity, the immaturity of the skin and an insufficient candida-static activity of the serum. The prematures and the newborns with an irregular birth are especially endangered. This danger is increased by simultaneous antibiotic therapy. The arising mycosis can reach from the relative harmless mouth- and diaper-thrush to serious septic diseases. An effective therapy therefore is very much desired. As new efficacious medicaments the derivates of imidazol, Clotrimazol, have proved satisfactory for the treatment of mycoses. It is as Canesten marketed. The drug possesses a strong activity against numerous fungi, some protozoa, and bacteria. In this paper it is reported on own pharmacokinetic and therapeutic investigations with Clotrimazol. The substance has been very useful for the treatment of mouth- and diaper-thrush. Clotrimazol was administered as BAYb 5097 peroral and local as Canesten -solution 1% and -cream 1%. There were 171 treatments carried out. Essential side-effects were not observed."} {"id": "PMID:1264012", "title": "[Surgical treatments of kinking of the internal carotid artery (author's transl)].", "content": "20 per cent of all patients we operated due to stenoses of the internal carotid artery were found to have kinking of the artery. Several methods of surgical treatment, among these resection of the kinking end-to-end anastomosis, and myoplasty using the digastric muscle are described. Angiography pre- and postoperatively is performed. Cerebral blood flow is measured by the 133 Xenon clearance.", "contents": "[Surgical treatments of kinking of the internal carotid artery (author's transl)]. 20 per cent of all patients we operated due to stenoses of the internal carotid artery were found to have kinking of the artery. Several methods of surgical treatment, among these resection of the kinking end-to-end anastomosis, and myoplasty using the digastric muscle are described. Angiography pre- and postoperatively is performed. Cerebral blood flow is measured by the 133 Xenon clearance."} {"id": "PMID:1264013", "title": "[Results of the treatment of diaphragmatic lesions (author's transl)].", "content": "During the period of 1959 to 1975 34 patients were operated at the Chirurgische Universitatsklinik Koln-Lindenthal because of lesions of the diaphragm. From the survivors 20 patients were examined again 2 to 15 years after operation. 15 patients (75%) stated subjective complaints. On these patients cicatrizations in the sinus phrenicocostalis, higher position of the diaphragm, axial hernia of the hiatus, restricted flexibility of the diaphragm, flattened diaphragm and paralysis of the diaphragm were found. More than 50% of the patients showed a significantly restricted total and vital capacity. Most important was the fact that in 25% of the reexamined patients there existed an axial hernia of the hiatus caused by the trauma.", "contents": "[Results of the treatment of diaphragmatic lesions (author's transl)]. During the period of 1959 to 1975 34 patients were operated at the Chirurgische Universitatsklinik Koln-Lindenthal because of lesions of the diaphragm. From the survivors 20 patients were examined again 2 to 15 years after operation. 15 patients (75%) stated subjective complaints. On these patients cicatrizations in the sinus phrenicocostalis, higher position of the diaphragm, axial hernia of the hiatus, restricted flexibility of the diaphragm, flattened diaphragm and paralysis of the diaphragm were found. More than 50% of the patients showed a significantly restricted total and vital capacity. Most important was the fact that in 25% of the reexamined patients there existed an axial hernia of the hiatus caused by the trauma."} {"id": "PMID:1264014", "title": "[One-stage resections in cases of carcinoma of the sigma and rectosigmoid (author's transl)].", "content": "210 one-stage resections of the sigma and 69 resections of the rectosigmoid were performed without a temporary proximal colostomy. Anastomotic leakage occurred in 4,7 and 2,9% respectively. Operative mortality was 3,5%. Comparing the results with the corresponding literature, it is shown, that the chosen operative procedure is a safe way of treatment.", "contents": "[One-stage resections in cases of carcinoma of the sigma and rectosigmoid (author's transl)]. 210 one-stage resections of the sigma and 69 resections of the rectosigmoid were performed without a temporary proximal colostomy. Anastomotic leakage occurred in 4,7 and 2,9% respectively. Operative mortality was 3,5%. Comparing the results with the corresponding literature, it is shown, that the chosen operative procedure is a safe way of treatment."} {"id": "PMID:1264038", "title": "Characterization of aberrations in image-intensified fluoroscopy.", "content": "A procedure is developed for characterizing and measuring the distortion and intensity variations which are present in x-ray image-intensifier systems. These effects often seriously limit the usefulness of such systems, and the results here make possible an evaluation and comparison of competing intensifier instruments.", "contents": "Characterization of aberrations in image-intensified fluoroscopy. A procedure is developed for characterizing and measuring the distortion and intensity variations which are present in x-ray image-intensifier systems. These effects often seriously limit the usefulness of such systems, and the results here make possible an evaluation and comparison of competing intensifier instruments."} {"id": "PMID:1264039", "title": "Biomedical probe using a fiber-optic coupled scintillator.", "content": "A high-sensitivity biomedical radiation probe which employs a fiber-optic coupled NaI(Tl) scintillator as a detector is described. It was developed for in vivo counting of low-energy 239Pu photons from material located in the tracheobronchial lymph nodes.-This probe is 20 times as sensitive as a solid-state probe (avalanche diode) previously developed for this application. Tests with 99mTc show a sensitivity more than 90 times greater than biomedical probes using DcTe of GaAs; however, the improved sensitivity is largely due to an increased sensitive volume. Probes were evaluated in animals and phantoms for detection of 239Pu and for location of lung tumors labeled with 111In.", "contents": "Biomedical probe using a fiber-optic coupled scintillator. A high-sensitivity biomedical radiation probe which employs a fiber-optic coupled NaI(Tl) scintillator as a detector is described. It was developed for in vivo counting of low-energy 239Pu photons from material located in the tracheobronchial lymph nodes.-This probe is 20 times as sensitive as a solid-state probe (avalanche diode) previously developed for this application. Tests with 99mTc show a sensitivity more than 90 times greater than biomedical probes using DcTe of GaAs; however, the improved sensitivity is largely due to an increased sensitive volume. Probes were evaluated in animals and phantoms for detection of 239Pu and for location of lung tumors labeled with 111In."} {"id": "PMID:1264040", "title": "Unequal weighting of given doses in opposed fields in treatment of cancer of the tonsillar region using 60Co, 4-, 8-, 15-, 24-MVp photons.", "content": "Weighting of given doses from parallel opposed fields is a widespread practice in radiation therapy of cancer in the tonsillar region. In order to determine when weighting is useful, dose distributions on the central axis were calculated for various energies (60Co, 4-, 8-, 15-, and MVp photons), weighting factors, and field separations. Criteria for judging the usefulness of weighting were (i) that variation in the dose across the tumor volume not exceed 10%, and (ii) that the dose to critical tissues outside the target volume be at least 20% less than target volume dose. The clinical situation that met these criteria was a lateral lesion that extended to less than one-third of the transverse diameter of the head, treated with either 60Co, 8, or 4 MVp with 4:1 weighting. Under these conditions, weighting was considered to be justified.", "contents": "Unequal weighting of given doses in opposed fields in treatment of cancer of the tonsillar region using 60Co, 4-, 8-, 15-, 24-MVp photons. Weighting of given doses from parallel opposed fields is a widespread practice in radiation therapy of cancer in the tonsillar region. In order to determine when weighting is useful, dose distributions on the central axis were calculated for various energies (60Co, 4-, 8-, 15-, and MVp photons), weighting factors, and field separations. Criteria for judging the usefulness of weighting were (i) that variation in the dose across the tumor volume not exceed 10%, and (ii) that the dose to critical tissues outside the target volume be at least 20% less than target volume dose. The clinical situation that met these criteria was a lateral lesion that extended to less than one-third of the transverse diameter of the head, treated with either 60Co, 8, or 4 MVp with 4:1 weighting. Under these conditions, weighting was considered to be justified."} {"id": "PMID:1264042", "title": "Reduced output of orthovoltage radiotherapy units.", "content": "Three causes of reduced output of orthovoltage radiotherapy units have recently been reported in this journal, each being due to faults external to the tube insert. A further incident is now reported where the output was reduced by 30% due to the tungsten foil becoming partially detached from the anode, while the unit continued to operate normally. The possible cause and the prevention of a repeat occurrence are discussed.", "contents": "Reduced output of orthovoltage radiotherapy units. Three causes of reduced output of orthovoltage radiotherapy units have recently been reported in this journal, each being due to faults external to the tube insert. A further incident is now reported where the output was reduced by 30% due to the tungsten foil becoming partially detached from the anode, while the unit continued to operate normally. The possible cause and the prevention of a repeat occurrence are discussed."} {"id": "PMID:1264041", "title": "Dosimetry of 137Cs sources with the Fletcher-Suit gynecological applicator.", "content": "Measurements were made in water about the tandem and ovoid structures of the Fletcher-Suit applicator loaded with a 137Cs source. The dose rate was found to vary as much as 25% as a result of differential absorption in the ovoid. Empirically based trigonometric expressions are suggested which provide the absorption correction as a function of the two angles of a spherical coordinate system. Computer calculated dose rates, with and without the absorption corrections, are compared.", "contents": "Dosimetry of 137Cs sources with the Fletcher-Suit gynecological applicator. Measurements were made in water about the tandem and ovoid structures of the Fletcher-Suit applicator loaded with a 137Cs source. The dose rate was found to vary as much as 25% as a result of differential absorption in the ovoid. Empirically based trigonometric expressions are suggested which provide the absorption correction as a function of the two angles of a spherical coordinate system. Computer calculated dose rates, with and without the absorption corrections, are compared."} {"id": "PMID:1264043", "title": "Size distribution of human albumin microspheres by forward scattering of monochromatic light.", "content": "Optical diffraction is used to study the structure of the Fourier transform of a thin suspension of human albumin microspheres. The intensity profile in the transform plane is then used to derive information about the particle size distribution.", "contents": "Size distribution of human albumin microspheres by forward scattering of monochromatic light. Optical diffraction is used to study the structure of the Fourier transform of a thin suspension of human albumin microspheres. The intensity profile in the transform plane is then used to derive information about the particle size distribution."} {"id": "PMID:1264044", "title": "Line-focusing x-ray monochromator for the analysis of trace elements in biological specimens.", "content": "A line-focusing x-ray monochromator has been designed and developed to be used with an energy dispersive detection system for the quantitative analysis of trace elements in biological specimens. This instrument uses a cylindrically curved Johansson-type crystal to monochromatize and focus the excitation radiation into a line 0.5 mm wide and 40 mm long. The excitation radiation chosen for these experiments was Mo Kalpha and the total intensity of the line-focused beam was estimated to be 2 X 10(7) cps. Because of the narrow width and high power density of the excitation between beam, small tissue specimens 1 X 1 X 12 mm in size along with a single strand of hair were analyzed for trace elements from Al through Sr. For the transition elements, concentrations of a few parts per million were easily detected with this analyzer.", "contents": "Line-focusing x-ray monochromator for the analysis of trace elements in biological specimens. A line-focusing x-ray monochromator has been designed and developed to be used with an energy dispersive detection system for the quantitative analysis of trace elements in biological specimens. This instrument uses a cylindrically curved Johansson-type crystal to monochromatize and focus the excitation radiation into a line 0.5 mm wide and 40 mm long. The excitation radiation chosen for these experiments was Mo Kalpha and the total intensity of the line-focused beam was estimated to be 2 X 10(7) cps. Because of the narrow width and high power density of the excitation between beam, small tissue specimens 1 X 1 X 12 mm in size along with a single strand of hair were analyzed for trace elements from Al through Sr. For the transition elements, concentrations of a few parts per million were easily detected with this analyzer."} {"id": "PMID:1264045", "title": "Demonstration of whole blood analysis using proton-induced x-ray emission.", "content": "The elemental variations in whole blood following gamma-radiation injury of mice have been studied. the trace-element analyses were performed using the proton-induced x-ray emission technique, and the results were compared with the red blood-cell count. It is shown that, by using this method, the variation of the six elements, K, Ca, Fe, Cu, Zn, and Rb, can be studied simultaneously.", "contents": "Demonstration of whole blood analysis using proton-induced x-ray emission. The elemental variations in whole blood following gamma-radiation injury of mice have been studied. the trace-element analyses were performed using the proton-induced x-ray emission technique, and the results were compared with the red blood-cell count. It is shown that, by using this method, the variation of the six elements, K, Ca, Fe, Cu, Zn, and Rb, can be studied simultaneously."} {"id": "PMID:1264061", "title": "Micro-scale two-dimensional polyacrylamide gell electrophoresis of ribosomal proteins.", "content": "A specially designed apparatus and conditions are described for the rapid analysis of ribosomal proteins by two-dimensional gel electrophoresis on a micro scale. The resolution of proteins in electropherograms is comparable to that obtained with other systems, but because of miniaturization, only 0.5 to 1 mug of each protein is required, and the entire procedure, including electrophoresis in both dimensions, and staining and destaining can be completed in 6 to 7 hours.", "contents": "Micro-scale two-dimensional polyacrylamide gell electrophoresis of ribosomal proteins. A specially designed apparatus and conditions are described for the rapid analysis of ribosomal proteins by two-dimensional gel electrophoresis on a micro scale. The resolution of proteins in electropherograms is comparable to that obtained with other systems, but because of miniaturization, only 0.5 to 1 mug of each protein is required, and the entire procedure, including electrophoresis in both dimensions, and staining and destaining can be completed in 6 to 7 hours."} {"id": "PMID:1264062", "title": "Genes inhibiting senescence in the ascomycete Podospora anserina.", "content": "Senescence occurs in all wild strains of Podospora anserina after continued growth. This syndrome can be inhibited by a synergistic interaction of two linked genes, incoloris and vivax. Whereas the wild strain starts to become senescent after 26 d and the mutants incoloris and vivax after 42 and 66 d respectively, the double mutant shows no signs of aging after culture for more than one year.", "contents": "Genes inhibiting senescence in the ascomycete Podospora anserina. Senescence occurs in all wild strains of Podospora anserina after continued growth. This syndrome can be inhibited by a synergistic interaction of two linked genes, incoloris and vivax. Whereas the wild strain starts to become senescent after 26 d and the mutants incoloris and vivax after 42 and 66 d respectively, the double mutant shows no signs of aging after culture for more than one year."} {"id": "PMID:1264063", "title": "Extrachromosomal inheritance in Schizosaccharomyces pombe. I. Evidence for an extrakaryotically inherited mutation conferring resistance to antimycin.", "content": "In crosses of [ANTr8] with auxotrophic strains, resistance to antimycin segregates almost 50:50 in random spore analysis with a slight preponderance for the sensitivity allele. Tetrad analysis, however, shows all possible types of tetrads (2:2; 3:1; 1:3; 4:0; 0:4 resistant versus sensitive) with an excess of 2:2 segregations and sectoring of colonies on antimycin medium indicating an extrachromosomal mode of inheritance. The overall ratio of resistant versus sensitive spores is the same as compared with random spore data. Using a mutant blocked in meiosis (mei 1) mitotic segregation of stable diploids is achieved, leading to a ratio of 20% resistant to 80% sensitive clones. Possible reasons for the bias in transmission of the resistance determinant is discussed.", "contents": "Extrachromosomal inheritance in Schizosaccharomyces pombe. I. Evidence for an extrakaryotically inherited mutation conferring resistance to antimycin. In crosses of [ANTr8] with auxotrophic strains, resistance to antimycin segregates almost 50:50 in random spore analysis with a slight preponderance for the sensitivity allele. Tetrad analysis, however, shows all possible types of tetrads (2:2; 3:1; 1:3; 4:0; 0:4 resistant versus sensitive) with an excess of 2:2 segregations and sectoring of colonies on antimycin medium indicating an extrachromosomal mode of inheritance. The overall ratio of resistant versus sensitive spores is the same as compared with random spore data. Using a mutant blocked in meiosis (mei 1) mitotic segregation of stable diploids is achieved, leading to a ratio of 20% resistant to 80% sensitive clones. Possible reasons for the bias in transmission of the resistance determinant is discussed."} {"id": "PMID:1264064", "title": "Extrachromosomal inheritance in Schizosaccharomyces pombe. II. Evidence for extrakaryotically inherited respiratory deficient mutants.", "content": "In contrast to the wild-type, mutant [ANTr8] is able spontaneously to throw off stable respiratory deficient mutants. The frequency of these mutants is considerably enhanced by treatment with ethidium bromide (EB) or the azo-dye Janus green (JG). An unstable cell state with a petite-like phenotype is found in both mutant [ANTr8] and wild-type after EB-treatment. However, only in the mutant is this unstable cell state followed by the appearance of stable respiratory deficient (RD) mutants. Formation of microcolonies is observed both in [ANTr8] and wild-type. RD mutants were isolated after EB treatment. Three of them (mit-12, mit-25, and mit-30) were analyzed and mit-25 characterized in more detail.", "contents": "Extrachromosomal inheritance in Schizosaccharomyces pombe. II. Evidence for extrakaryotically inherited respiratory deficient mutants. In contrast to the wild-type, mutant [ANTr8] is able spontaneously to throw off stable respiratory deficient mutants. The frequency of these mutants is considerably enhanced by treatment with ethidium bromide (EB) or the azo-dye Janus green (JG). An unstable cell state with a petite-like phenotype is found in both mutant [ANTr8] and wild-type after EB-treatment. However, only in the mutant is this unstable cell state followed by the appearance of stable respiratory deficient (RD) mutants. Formation of microcolonies is observed both in [ANTr8] and wild-type. RD mutants were isolated after EB treatment. Three of them (mit-12, mit-25, and mit-30) were analyzed and mit-25 characterized in more detail."} {"id": "PMID:1264075", "title": "Partial reversible inactivation of enzymes due to binding to the human erythrocyte membrane.", "content": "Hypotonic human erythrocyte ghosts, devoid of the original glyceraldehyde-3-phosphate dehydrogenase content of the red cell, bind added glyceraldehyde-3-phosphate dehydrogenases, isolated from human erythrocytes, rabbit and pig muscle, as well as rabbit muscle aldolase. There are only slight differences in the affinities towards the various glyceraldehyde-3-phosphate dehydrogenases. On the other hand, glyceraldehyde-3-phosphate dehydrogenases are bound much stronger than aldolase; in an equimolar mixture the former can prevent the binding of the latter, or replace previously bound aldolase at the membrane surface. Binding is always accompanied by the partial inactivation of enzymes, which can be reverted by desorption. Unwashed ghosts rich in hemoglobin seem to have a more pronounced inactivating effect on bound glyceraldehyde-3-phosphate dehydrogenase. In isotonic media ghosts, whether white or unwashed, reseal and do not interact with the enzymes.", "contents": "Partial reversible inactivation of enzymes due to binding to the human erythrocyte membrane. Hypotonic human erythrocyte ghosts, devoid of the original glyceraldehyde-3-phosphate dehydrogenase content of the red cell, bind added glyceraldehyde-3-phosphate dehydrogenases, isolated from human erythrocytes, rabbit and pig muscle, as well as rabbit muscle aldolase. There are only slight differences in the affinities towards the various glyceraldehyde-3-phosphate dehydrogenases. On the other hand, glyceraldehyde-3-phosphate dehydrogenases are bound much stronger than aldolase; in an equimolar mixture the former can prevent the binding of the latter, or replace previously bound aldolase at the membrane surface. Binding is always accompanied by the partial inactivation of enzymes, which can be reverted by desorption. Unwashed ghosts rich in hemoglobin seem to have a more pronounced inactivating effect on bound glyceraldehyde-3-phosphate dehydrogenase. In isotonic media ghosts, whether white or unwashed, reseal and do not interact with the enzymes."} {"id": "PMID:1264077", "title": "[Significance of diagnostic parameters in recurrent urinary tract infection in children. I. The history (author's transl)].", "content": "Comparison of the history of 136 children with recurrent urinary tract infection (UTI) with their follow up in a special urologic service (260,6 patient years) showed marked differences in symptoms of recurrent UTI prior to follow up (769 \"anamnestic\" recurrent UTI) as compared to true significant bacteriuria (278 recurrent UTI during follow up). Therefore parents statements about time of first UTI and incidence of further recurrences should be considered with caution. Only 10% of the physicians proved their diagnosis \"UTI\" bacteriologically. Anamnestic data, however, are of great importance for the follow up of children with recurrent UTI: children with many recurrences in their history have a greater risk of further recurrences despite careful follow up, and tend to have more pathologic findings on first radiologic examinations.", "contents": "[Significance of diagnostic parameters in recurrent urinary tract infection in children. I. The history (author's transl)]. Comparison of the history of 136 children with recurrent urinary tract infection (UTI) with their follow up in a special urologic service (260,6 patient years) showed marked differences in symptoms of recurrent UTI prior to follow up (769 \"anamnestic\" recurrent UTI) as compared to true significant bacteriuria (278 recurrent UTI during follow up). Therefore parents statements about time of first UTI and incidence of further recurrences should be considered with caution. Only 10% of the physicians proved their diagnosis \"UTI\" bacteriologically. Anamnestic data, however, are of great importance for the follow up of children with recurrent UTI: children with many recurrences in their history have a greater risk of further recurrences despite careful follow up, and tend to have more pathologic findings on first radiologic examinations."} {"id": "PMID:1264076", "title": "Lipid-F1 nucleohistone interactions.", "content": "High concentrations of phospholipids determine destabilization of F1 histone-DNA complex at the weight ratios, histone:DNA, 0.8:1 and 1:1, but low concentrations cause only negligible destabilization. Cholesterol at high weight ratios has little effect on nucleohistone stability. Only linolenic acid of the fatty acids used reproduces similar changes in the thermal stability of F1 histone-DNA complex as phospholipids. The type of interaction of phospholipids with the F1 histone-DNA complex is analyzed, and the involvement of phospholipids in DNA replication in vivo is discussed.", "contents": "Lipid-F1 nucleohistone interactions. High concentrations of phospholipids determine destabilization of F1 histone-DNA complex at the weight ratios, histone:DNA, 0.8:1 and 1:1, but low concentrations cause only negligible destabilization. Cholesterol at high weight ratios has little effect on nucleohistone stability. Only linolenic acid of the fatty acids used reproduces similar changes in the thermal stability of F1 histone-DNA complex as phospholipids. The type of interaction of phospholipids with the F1 histone-DNA complex is analyzed, and the involvement of phospholipids in DNA replication in vivo is discussed."} {"id": "PMID:1264078", "title": "[Hyposensitization with extracts of house dust and mites adsorbed on aluminium-hydroxyde (allpyral) in children with bronchial asthma (author's transl)].", "content": "Since the year 1971 the authors have treated 39 asthmatic patients with Allpyral house dust vaccins containing Dermatophagoides farinae extract. 16 of these children previously had similar treatment, but without mite extract, and this was changed because of the poor results. Patients allergic only to house dust and mites were selected according to the skin tests. Skin reaction to mite extract did not change even in symptomfree children in contrast to the decrease or disappearance of skin sensitivity to house dust. 23 out of 39 patients had no symptoms or only mild and short wheezing occasionaly in the last 3-6 months of treatment. There were six patients whose symptoms remained unchanged during the treatment. These children were all among the 16 asthmatics who previously had an unsuccessful house dust hyposensitization. So every patient whose treatment was started with the combined house dust-mite Allpyral has imporved, only 5 of the 23 still had yet a few asthmatic attacks.", "contents": "[Hyposensitization with extracts of house dust and mites adsorbed on aluminium-hydroxyde (allpyral) in children with bronchial asthma (author's transl)]. Since the year 1971 the authors have treated 39 asthmatic patients with Allpyral house dust vaccins containing Dermatophagoides farinae extract. 16 of these children previously had similar treatment, but without mite extract, and this was changed because of the poor results. Patients allergic only to house dust and mites were selected according to the skin tests. Skin reaction to mite extract did not change even in symptomfree children in contrast to the decrease or disappearance of skin sensitivity to house dust. 23 out of 39 patients had no symptoms or only mild and short wheezing occasionaly in the last 3-6 months of treatment. There were six patients whose symptoms remained unchanged during the treatment. These children were all among the 16 asthmatics who previously had an unsuccessful house dust hyposensitization. So every patient whose treatment was started with the combined house dust-mite Allpyral has imporved, only 5 of the 23 still had yet a few asthmatic attacks."} {"id": "PMID:1264079", "title": "[Pre-, peri- and and postnatal prevention of major neuropediatric handicaps in Sweden (author's transl)].", "content": "The actual distribution and panorama changes of neuropediatric handicaps in Sweden as well as modern aspects on prevention are presented. The following conclusions are drawn. Preventive programs directed towards brain damaging factors occurring after the neonatal period are more or less completed. Further gains, however moderate, should be attainable perinatally. The largest number of unsolved problems and today the most challenging, refer to secondary fetal brain dysfunction during the prenatal period, particularly the 3rd trimester.", "contents": "[Pre-, peri- and and postnatal prevention of major neuropediatric handicaps in Sweden (author's transl)]. The actual distribution and panorama changes of neuropediatric handicaps in Sweden as well as modern aspects on prevention are presented. The following conclusions are drawn. Preventive programs directed towards brain damaging factors occurring after the neonatal period are more or less completed. Further gains, however moderate, should be attainable perinatally. The largest number of unsolved problems and today the most challenging, refer to secondary fetal brain dysfunction during the prenatal period, particularly the 3rd trimester."} {"id": "PMID:1264088", "title": "[Distance and velocity standards for head circimference growth before and after term until 18 months--results from a longitudinal study (author's transl)].", "content": "Standards for head circumference growth (distance and velocity) from the perinatal period until the age of 18 months have been based on repeated measurements at short intervals (longitudinal) in 60 appropriate for gestational age (AGA) preterm infants of very low fetal age, and 68 full term infants. Moreover the growth of 32 small for gestational age (SGA) preterm infants has been evaluated. Before term the extrauterine head growth curve is similar to that of \"intrauterine curves\". At term and until the age of 18 months the growth curves of AGA preterm infants agree well with those of the full term controls, without statistically significant differences (p greater than 0.1). If the age is not corrected for prematurity ther is a significant difference between preterm and full term infants until 17 months (p less than 0.05). With decreasing velocity of head circumference growth this difference becomes non-significant at the age of 18 months (p greater than 0.1). Out of the heterogenious group of 32 SGA preterm infants 15 have shown a catch-up growth in head circumference until the third month, whereas 17 infants remained significantly below the growth curve of the AGA. Growth velocity of head circumference, calculated in cm/month, in the last 10 weeks before term is significantly higher (p less 0.025) than later on, with a mean peak of 4.3 cm in the 34th postmentstrual week. After term, the velocity curve of the AGA preterm infants agrees with that of the full term controls. A period of rapid head circumference growth -- a growth spurt -- extends from the 31st postmenstrual week until the 6th month after term. In the following months the velocity curves flatten. If the age is not corrected for prematurity, the peak of the velocity curve becomes flat and spread with a mean growth velocity of 3.0 cm in the first, of 3.4 cm in the second and of 2.5 cm in the third month.", "contents": "[Distance and velocity standards for head circimference growth before and after term until 18 months--results from a longitudinal study (author's transl)]. Standards for head circumference growth (distance and velocity) from the perinatal period until the age of 18 months have been based on repeated measurements at short intervals (longitudinal) in 60 appropriate for gestational age (AGA) preterm infants of very low fetal age, and 68 full term infants. Moreover the growth of 32 small for gestational age (SGA) preterm infants has been evaluated. Before term the extrauterine head growth curve is similar to that of \"intrauterine curves\". At term and until the age of 18 months the growth curves of AGA preterm infants agree well with those of the full term controls, without statistically significant differences (p greater than 0.1). If the age is not corrected for prematurity ther is a significant difference between preterm and full term infants until 17 months (p less than 0.05). With decreasing velocity of head circumference growth this difference becomes non-significant at the age of 18 months (p greater than 0.1). Out of the heterogenious group of 32 SGA preterm infants 15 have shown a catch-up growth in head circumference until the third month, whereas 17 infants remained significantly below the growth curve of the AGA. Growth velocity of head circumference, calculated in cm/month, in the last 10 weeks before term is significantly higher (p less 0.025) than later on, with a mean peak of 4.3 cm in the 34th postmentstrual week. After term, the velocity curve of the AGA preterm infants agrees with that of the full term controls. A period of rapid head circumference growth -- a growth spurt -- extends from the 31st postmenstrual week until the 6th month after term. In the following months the velocity curves flatten. If the age is not corrected for prematurity, the peak of the velocity curve becomes flat and spread with a mean growth velocity of 3.0 cm in the first, of 3.4 cm in the second and of 2.5 cm in the third month."} {"id": "PMID:1264089", "title": "[The longitudinal increase of the internal jugular vein and the upper v. cava as measured between the mastoid to the heart: parameter for timing the re-operation after ventriculocardiostomy (author's transl)].", "content": "Some time after ventriculo-cardiostomy in children with hydrocephalus the cardiac catheter is retracting out of the right atrium into the upper veins due to the increase of body length during growth. This might endanger proper functioning of the valve. Therefore most authors are in favour of a prophylactic elongation of the catheter by re-operation. In order to roughly predict the time for re-operation we measured course of the catheter in 4120 children. As a basis for long time supervision of children with this shunt operation we thus propose a curve of length increase of the blood vessels concerned, based on our data, in connection with the known curve of length increase of the body.", "contents": "[The longitudinal increase of the internal jugular vein and the upper v. cava as measured between the mastoid to the heart: parameter for timing the re-operation after ventriculocardiostomy (author's transl)]. Some time after ventriculo-cardiostomy in children with hydrocephalus the cardiac catheter is retracting out of the right atrium into the upper veins due to the increase of body length during growth. This might endanger proper functioning of the valve. Therefore most authors are in favour of a prophylactic elongation of the catheter by re-operation. In order to roughly predict the time for re-operation we measured course of the catheter in 4120 children. As a basis for long time supervision of children with this shunt operation we thus propose a curve of length increase of the blood vessels concerned, based on our data, in connection with the known curve of length increase of the body."} {"id": "PMID:1264090", "title": "[Heredo familial areflectoric dystasie. Roussy-L\u00e9vy-Syndrome (author's transl)].", "content": "The Roussy-L\u00e9vy-Syndrome in a 12 years old girl is described and its relation to other heredofamilial ataxias is discussed. The kindred of our patient was studied as well. Information about 21 family members could be collected; 11 of them also suffered from RLS. Additionally for the first time in literature, dermatoglyphic patterns in these patients have been investigated.", "contents": "[Heredo familial areflectoric dystasie. Roussy-L\u00e9vy-Syndrome (author's transl)]. The Roussy-L\u00e9vy-Syndrome in a 12 years old girl is described and its relation to other heredofamilial ataxias is discussed. The kindred of our patient was studied as well. Information about 21 family members could be collected; 11 of them also suffered from RLS. Additionally for the first time in literature, dermatoglyphic patterns in these patients have been investigated."} {"id": "PMID:1264091", "title": "[Unviable micromelic dwarfism: a syndrome with dystrophy of the thorax and polydaktyly type Saldino-Noonan (author's transl)].", "content": "Besides classical achondroplasia various severe osteochondrodysplastic disorders have been differentiated in recent years. Their most important features include obligatory perinatal mortality, severe dystrophy of the thorax and shortening of tubular bones. Additionally some of these syndromes present visceral malformations, cleft-lip, and malformations of the genitals. A detailed case report of a patient is given. Various features: dystrophy of the thorax, micromelia, postaxial polydactyly, metaphyseal dysplasia, malformations of the great vessels, and polcystic kidney suggest the classification as short rib-polydactyly syndrome, type Saldino-Noonan.", "contents": "[Unviable micromelic dwarfism: a syndrome with dystrophy of the thorax and polydaktyly type Saldino-Noonan (author's transl)]. Besides classical achondroplasia various severe osteochondrodysplastic disorders have been differentiated in recent years. Their most important features include obligatory perinatal mortality, severe dystrophy of the thorax and shortening of tubular bones. Additionally some of these syndromes present visceral malformations, cleft-lip, and malformations of the genitals. A detailed case report of a patient is given. Various features: dystrophy of the thorax, micromelia, postaxial polydactyly, metaphyseal dysplasia, malformations of the great vessels, and polcystic kidney suggest the classification as short rib-polydactyly syndrome, type Saldino-Noonan."} {"id": "PMID:1264097", "title": "[Possibilities of extension of blood group determination in cases of disputed paternity].", "content": "Results of the blood-group testing carried out in 1966-1974 in cases of discussed paternity are described in detail. Until 1970 only blood groups A1, A2, BO, MN and systems of Hp Rh and Gm (a) were tested (so called fundamental-testing). Maximal chance of exclusion of paternity on the base of these systems 70%. From 1970 on, the investigation have been extended to systems Gm (b), Gm(x), INV (1), Ss, Kell-Cellano, Duffy and during the last two years to systems of Gc, acid-phosphatase of erythrocytes and glutamat-pyruvat-transaminase. Thus the maximal chance of exclusion of paternity increased to 90%. Chances of exclusion on the base of every system are discussed separately also in detail. Fundamental-test were carried out in 10 200 cases, extended-tests in 278 cases. On the base of fundamental-tests exclusion of paternity could be achieved in 32, 85% of the cases. In 1974 in 374 (32, 21%) cases out of 1161 by fundamentaltesting, in further 100 (8,61%) cases by extended testing altogether in 474 (40,82%) cases- could be achieved exclusion of the paternity. These data indicate effectivity and reasonableness of the extension of blood-grouping-testing.", "contents": "[Possibilities of extension of blood group determination in cases of disputed paternity]. Results of the blood-group testing carried out in 1966-1974 in cases of discussed paternity are described in detail. Until 1970 only blood groups A1, A2, BO, MN and systems of Hp Rh and Gm (a) were tested (so called fundamental-testing). Maximal chance of exclusion of paternity on the base of these systems 70%. From 1970 on, the investigation have been extended to systems Gm (b), Gm(x), INV (1), Ss, Kell-Cellano, Duffy and during the last two years to systems of Gc, acid-phosphatase of erythrocytes and glutamat-pyruvat-transaminase. Thus the maximal chance of exclusion of paternity increased to 90%. Chances of exclusion on the base of every system are discussed separately also in detail. Fundamental-test were carried out in 10 200 cases, extended-tests in 278 cases. On the base of fundamental-tests exclusion of paternity could be achieved in 32, 85% of the cases. In 1974 in 374 (32, 21%) cases out of 1161 by fundamentaltesting, in further 100 (8,61%) cases by extended testing altogether in 474 (40,82%) cases- could be achieved exclusion of the paternity. These data indicate effectivity and reasonableness of the extension of blood-grouping-testing."} {"id": "PMID:1264098", "title": "[Anthropological studies as a possible tool in disputed paternity cases].", "content": "Author on the base of the material investigated in the Department of Forensic Medicine of Semmelweis Medical University discusses importance of anthropological investigations as a valuable, additional to serology test. Data obtained by the investigation of 2000 families demonstrate the hereditary features and their value as an evidence in a filiation cases. Author emphasizes the importance of the chromosome-investigations as one of the most reliable methods in paternity cases.", "contents": "[Anthropological studies as a possible tool in disputed paternity cases]. Author on the base of the material investigated in the Department of Forensic Medicine of Semmelweis Medical University discusses importance of anthropological investigations as a valuable, additional to serology test. Data obtained by the investigation of 2000 families demonstrate the hereditary features and their value as an evidence in a filiation cases. Author emphasizes the importance of the chromosome-investigations as one of the most reliable methods in paternity cases."} {"id": "PMID:1264099", "title": "[The work at the Toxicology Laboratory of the Institute for Forensic Medicine].", "content": "The author gives an account on the work of the department laboratory of the Department of Forensic Medicine of Semmelweis Medical University. The laboratory was founded 15 years ago. The work, consist of a large number of routine investigations, inspite of that manysided, sometimes complicated. Author emphasizes the necessity of the use of principally different chemical methods in the solution of the same problem and importance of parallel measurements for the sake of reliability and accuracy.", "contents": "[The work at the Toxicology Laboratory of the Institute for Forensic Medicine]. The author gives an account on the work of the department laboratory of the Department of Forensic Medicine of Semmelweis Medical University. The laboratory was founded 15 years ago. The work, consist of a large number of routine investigations, inspite of that manysided, sometimes complicated. Author emphasizes the necessity of the use of principally different chemical methods in the solution of the same problem and importance of parallel measurements for the sake of reliability and accuracy."} {"id": "PMID:1264100", "title": "[Various problems concerning maternal mortality during pregnancy].", "content": "In the autopsy material of the Department of Forensic Medicine of the Semmelweis Medical University--90,000 cases in 25 years (1950-1975)--508 cases of death in the period of gestation have occurred. Author have analysed this material and have established, that in every second case the death occurred due to criminal abortion, in every fifth case due to the complications of the pregnancy and in every third case due to the complications of delivery. By means of trend-calculations it was further established that in the autopsy material of the Department the number of the sudden natural death of women in the reproductive age during the 25 years remained on the same level, but the number of death cases connected with gestation decreased. In the latter group: the number of death cases due to abortion and complications of pregnancy decreased significantly, number of lethal cases due to complications of delivery remained at the same level. Data of the analysis are compared to the data reported in the literature. Some questions--the cause of the death, the criminality when abortions are concerned, questions of the treatment and the responsibility of physicians are also discussed. These investigations seem to evidence that on the base of the evaluation of a large autopsy material the legal medicine can reveal valuable data for the preventive medicine.", "contents": "[Various problems concerning maternal mortality during pregnancy]. In the autopsy material of the Department of Forensic Medicine of the Semmelweis Medical University--90,000 cases in 25 years (1950-1975)--508 cases of death in the period of gestation have occurred. Author have analysed this material and have established, that in every second case the death occurred due to criminal abortion, in every fifth case due to the complications of the pregnancy and in every third case due to the complications of delivery. By means of trend-calculations it was further established that in the autopsy material of the Department the number of the sudden natural death of women in the reproductive age during the 25 years remained on the same level, but the number of death cases connected with gestation decreased. In the latter group: the number of death cases due to abortion and complications of pregnancy decreased significantly, number of lethal cases due to complications of delivery remained at the same level. Data of the analysis are compared to the data reported in the literature. Some questions--the cause of the death, the criminality when abortions are concerned, questions of the treatment and the responsibility of physicians are also discussed. These investigations seem to evidence that on the base of the evaluation of a large autopsy material the legal medicine can reveal valuable data for the preventive medicine."} {"id": "PMID:1264101", "title": "[Topo-optical demonstration of lineal arrangement of vicial OH radicals by means of aldehyde bisulfite toluidine blue (ABT) reaction].", "content": "Topo-optical reaction with aldehyd-bisulfit-toluidinblue (ABT) suitable for the demonstration of lineal arrangement of vicinal OH-radicals is described. On the base of double refringement brought about by the orientated dye-binding, this reaction is suitable for the study of molecular arrangement of carbohydrate components of biological structures (glycoproteins, glycolipides and polysaccharides). Double refringement brought about by the reaction ABT optically is negative to the length of polysaccharide-chains. Practical use of the method is demonstrated on several biological structures. Findings show, that reaction ABT opens new possibilities for the study of ultrastructure of carbohydrate components of various tissue elements.", "contents": "[Topo-optical demonstration of lineal arrangement of vicial OH radicals by means of aldehyde bisulfite toluidine blue (ABT) reaction]. Topo-optical reaction with aldehyd-bisulfit-toluidinblue (ABT) suitable for the demonstration of lineal arrangement of vicinal OH-radicals is described. On the base of double refringement brought about by the orientated dye-binding, this reaction is suitable for the study of molecular arrangement of carbohydrate components of biological structures (glycoproteins, glycolipides and polysaccharides). Double refringement brought about by the reaction ABT optically is negative to the length of polysaccharide-chains. Practical use of the method is demonstrated on several biological structures. Findings show, that reaction ABT opens new possibilities for the study of ultrastructure of carbohydrate components of various tissue elements."} {"id": "PMID:1264102", "title": "[Demonstration of bacteria and fungi in tissues by topo-optic aldehyde bisulfite toluidine blue (ABT) reaction].", "content": "Reaction with aldehyd-bisulfit-toluidinblue (ABT)--as a selective topo-optical reaction for vicinal OH-and amino-OH groups, appears to be suitable for demonstration of bacteria in tissues. Cell membranes and capsules of bacteria and fungi contain large quantity of carbo-hydrates, therefore they show strong basophilic staining after ABT reaction. Double refringement brought about by orientated dye-binding seems to be the sign of the linear arrangement of polysaccharides composing cell membranes and capsules of bacteria. Practical importance of the reaction is shown on examples. Diagnostic advantages of it are also discussed.", "contents": "[Demonstration of bacteria and fungi in tissues by topo-optic aldehyde bisulfite toluidine blue (ABT) reaction]. Reaction with aldehyd-bisulfit-toluidinblue (ABT)--as a selective topo-optical reaction for vicinal OH-and amino-OH groups, appears to be suitable for demonstration of bacteria in tissues. Cell membranes and capsules of bacteria and fungi contain large quantity of carbo-hydrates, therefore they show strong basophilic staining after ABT reaction. Double refringement brought about by orientated dye-binding seems to be the sign of the linear arrangement of polysaccharides composing cell membranes and capsules of bacteria. Practical importance of the reaction is shown on examples. Diagnostic advantages of it are also discussed."} {"id": "PMID:1264103", "title": "[Selective demonstration of amloid deposits and methodical possibilities for the analysis of ultrastructural differences].", "content": "In preparations stained by congo-rot and covered with arabic gumm amyloid deposits reveal intensive, positive bi refringement, collagen is isotrop, or shows a mild bi refringement. This method is most suitable for selective optical demonstration of amyloid deposits. On the base of investigation of ultrastructural stability of amyloid deposits (resistency to performiat and induced proteolysis) two types of them may be distinguished: I. amyloid deposits of labile structure (generalized, secondary amyloidosis) and 2. amyloid deposits of stabile structure (generalized primary amyloidosis, local and senile amyloid deposits).", "contents": "[Selective demonstration of amloid deposits and methodical possibilities for the analysis of ultrastructural differences]. In preparations stained by congo-rot and covered with arabic gumm amyloid deposits reveal intensive, positive bi refringement, collagen is isotrop, or shows a mild bi refringement. This method is most suitable for selective optical demonstration of amyloid deposits. On the base of investigation of ultrastructural stability of amyloid deposits (resistency to performiat and induced proteolysis) two types of them may be distinguished: I. amyloid deposits of labile structure (generalized, secondary amyloidosis) and 2. amyloid deposits of stabile structure (generalized primary amyloidosis, local and senile amyloid deposits)."} {"id": "PMID:1264104", "title": "[Electron microscopic changes in the myocardium in experimental carbon monoxide poisoning].", "content": "Effect of coal-gas poisoning on the myocard was studied by the aid of electron microscope and electronmicroscopic histochemistry. Alterations revealed can not be regarded as specific ones, they seem to be of hypoxic origin. Activity of the cytochromoxidase--as revealed by electronmicroscopic histochemistry--in cases of coal-gas poisoning decreases. Specificity of the cytochromoxidase method and the leadsalt method of the demonstration of calcium are discussed.", "contents": "[Electron microscopic changes in the myocardium in experimental carbon monoxide poisoning]. Effect of coal-gas poisoning on the myocard was studied by the aid of electron microscope and electronmicroscopic histochemistry. Alterations revealed can not be regarded as specific ones, they seem to be of hypoxic origin. Activity of the cytochromoxidase--as revealed by electronmicroscopic histochemistry--in cases of coal-gas poisoning decreases. Specificity of the cytochromoxidase method and the leadsalt method of the demonstration of calcium are discussed."} {"id": "PMID:1264105", "title": "[Possibilities of the use of electron microscopy in forensic medicine].", "content": "Author deals with possibilities of application of scanning electron microscopy in the medico-legal practice. After a short review of the literature methodological problems are discussed and the author's experiences are reported. Author have investigated various injuries of hair, bonetissue, and skin specimens. It was established that they reveal characteristic changes which can be easily observed by scanning-electron-microscope. Various injuries of hair-cutting, tearing, breakage, burning etc.-have distinguishable characteristics. Scanning electron microscopy is suitable for the study of vital and postmortal injuries.", "contents": "[Possibilities of the use of electron microscopy in forensic medicine]. Author deals with possibilities of application of scanning electron microscopy in the medico-legal practice. After a short review of the literature methodological problems are discussed and the author's experiences are reported. Author have investigated various injuries of hair, bonetissue, and skin specimens. It was established that they reveal characteristic changes which can be easily observed by scanning-electron-microscope. Various injuries of hair-cutting, tearing, breakage, burning etc.-have distinguishable characteristics. Scanning electron microscopy is suitable for the study of vital and postmortal injuries."} {"id": "PMID:1264106", "title": "Critical periods of the mitotic cycle: influence of aminopterin and thymidine on production of chromosomal aberrations by radiation in Crepis capillaris.", "content": "The influence of aminopterin (AP), tritiated thymidine ([3H] TdR) and \"cold\" thymidine (TdR) on production of chromosomal aberrations in meristematic cells of Crepis capillaris irradiated in different stages of the mitotic cycle with 300 rad of 63Co gamma-rays was studied. All the chemical treatments increased most of all the frequency of aberrations induced during two \"critical periods\" localized before the stage of DNA synthesis (fixation 9 h after irradiation) and before that of mitosis (4 h). Treatments with TdR and [3H]TdR increased most of all the frequency of chromatid aberrations when irradiation was performed in G1, and the frequency of gaps when irradiated in G2. Treatment with AP increased the yield of different types of aberration more uniformly. The modifying effect of the chemicals tested appeared to be independent of replicative synthesis. The \"critical periods\" are suggested to be the stages when regular \"proof reading\" and correction of spontaneous errors takes place [9,13]. In addition to this regular mechanism, radiation induces an \"emergency\" mechanism of repair. AP inhibits the mechanism of regular repair; in addition TdR and [3H] TdR suppress the lateral spread of primary injuries across the chromosome.", "contents": "Critical periods of the mitotic cycle: influence of aminopterin and thymidine on production of chromosomal aberrations by radiation in Crepis capillaris. The influence of aminopterin (AP), tritiated thymidine ([3H] TdR) and \"cold\" thymidine (TdR) on production of chromosomal aberrations in meristematic cells of Crepis capillaris irradiated in different stages of the mitotic cycle with 300 rad of 63Co gamma-rays was studied. All the chemical treatments increased most of all the frequency of aberrations induced during two \"critical periods\" localized before the stage of DNA synthesis (fixation 9 h after irradiation) and before that of mitosis (4 h). Treatments with TdR and [3H]TdR increased most of all the frequency of chromatid aberrations when irradiation was performed in G1, and the frequency of gaps when irradiated in G2. Treatment with AP increased the yield of different types of aberration more uniformly. The modifying effect of the chemicals tested appeared to be independent of replicative synthesis. The \"critical periods\" are suggested to be the stages when regular \"proof reading\" and correction of spontaneous errors takes place [9,13]. In addition to this regular mechanism, radiation induces an \"emergency\" mechanism of repair. AP inhibits the mechanism of regular repair; in addition TdR and [3H] TdR suppress the lateral spread of primary injuries across the chromosome."} {"id": "PMID:1264107", "title": "Clastogenic effects of methylnitrosourea and ethylnitrosourea on chromosomes from human fibroblast cell lines.", "content": "Human fibroblast cell lines were pulse-treated for 1 h with either methylnitrosourea (MNU) or ethylnitrosourea (ENU) at various time intervals before harvesting for chromosome analysis. Cells treated with 1 X 10(-3) M, 5 X 10(-4) M, and 1 X 10(-4) M final concentrations of MNU and ENU during the G2 or M phases of the cell cycle showed a significant increase in chromatid-type abnormalities over controls. Cells exposed to MNU or ENU 23 h before harvest showed some chromosome-type abnormalities, reflecting probable damage induced during the G1 phase of the cell cycle or derived from chromatid damage induced during the previous cell cycle. The mitotic indices and incidences of abnormalities suggested a dose response effect when cells were treated with the two higher concentrations and the three concentrations, respectively, of MNU or ENU. Chromatid abnormalities were observed in MUN and ENU-treated cells from each of four cell lines. From this investigation, it was concluded that MNU and ENU treatment of human diploid cell lines in vitro induced both chromatid and chromosome aberrations. MNU and ENU, both of which had previously been shown to be mutagenic in experimental animals, are, therefore, also considered to be mutagenic at the chromosome level in human fibroblasts grown and treated in cell culture.", "contents": "Clastogenic effects of methylnitrosourea and ethylnitrosourea on chromosomes from human fibroblast cell lines. Human fibroblast cell lines were pulse-treated for 1 h with either methylnitrosourea (MNU) or ethylnitrosourea (ENU) at various time intervals before harvesting for chromosome analysis. Cells treated with 1 X 10(-3) M, 5 X 10(-4) M, and 1 X 10(-4) M final concentrations of MNU and ENU during the G2 or M phases of the cell cycle showed a significant increase in chromatid-type abnormalities over controls. Cells exposed to MNU or ENU 23 h before harvest showed some chromosome-type abnormalities, reflecting probable damage induced during the G1 phase of the cell cycle or derived from chromatid damage induced during the previous cell cycle. The mitotic indices and incidences of abnormalities suggested a dose response effect when cells were treated with the two higher concentrations and the three concentrations, respectively, of MNU or ENU. Chromatid abnormalities were observed in MUN and ENU-treated cells from each of four cell lines. From this investigation, it was concluded that MNU and ENU treatment of human diploid cell lines in vitro induced both chromatid and chromosome aberrations. MNU and ENU, both of which had previously been shown to be mutagenic in experimental animals, are, therefore, also considered to be mutagenic at the chromosome level in human fibroblasts grown and treated in cell culture."} {"id": "PMID:1264108", "title": "Analysis of intercellular distributions of chromatid aberrations.", "content": "59 intercellular distributions of chemically induced and spontaneous chromatid aberrations were analyzed for goodness of fit in respect of the Poisson (PD), the geometrical (GD), and the negative binomial distributions (NBD). The data are excellently described by the NBD. This distribution can be deduced from a model out of the queueing theory and is based on the hypothesis of restitution. Estimators are obtained for the ratio of restitution and induction processes involved in the origin of chromosomal aberrations.", "contents": "Analysis of intercellular distributions of chromatid aberrations. 59 intercellular distributions of chemically induced and spontaneous chromatid aberrations were analyzed for goodness of fit in respect of the Poisson (PD), the geometrical (GD), and the negative binomial distributions (NBD). The data are excellently described by the NBD. This distribution can be deduced from a model out of the queueing theory and is based on the hypothesis of restitution. Estimators are obtained for the ratio of restitution and induction processes involved in the origin of chromosomal aberrations."} {"id": "PMID:1264109", "title": "Chromosome aberration yields in human lymphocytes induced by fractionated doses of x-radiation.", "content": "Unstimulated (G0) human peripheral blood lymphocytes were exposed at 37 degrees C to doses of 200 or 500 rad of X-rays delivered in two equal fractions. The dose fractions were separated by intervals of up to 7 h in the 200 rad study and up to 48 h for 500 rad. In both studies the mean levels of dicentrics and total unstable aberrations began to decline when fractions were delivered with intervals of greater than 2 h. With 200 rad the yield had decreased to an additive baseline (i.e. equal to only twice the yield of a single 100-rad fraction) by an interval of 4 h. Following 500 rad the yield declined until 8 h and then remained 20% above the additive baseline even when 48 h separated the fractions. Possible explanations for this discrepancy are discussed. In a second experiment PHA stimulated lymphocyte cultures were exposed to 2 doses of 125 rad of X-rays up to 7 h apart in an attempt to demonstrate the late peak in aberration yields originally reported by Lane [5]. Control cultures received unsplit doses of 250 rad at the time of the corresponding second 125-rad fraction. No evidence of a late peak in dicentric yield was observed. The yield remained approximately the same irrespective of the time interval between fractions but these split dose yields were significantly different from the accompanying unsplit controls.", "contents": "Chromosome aberration yields in human lymphocytes induced by fractionated doses of x-radiation. Unstimulated (G0) human peripheral blood lymphocytes were exposed at 37 degrees C to doses of 200 or 500 rad of X-rays delivered in two equal fractions. The dose fractions were separated by intervals of up to 7 h in the 200 rad study and up to 48 h for 500 rad. In both studies the mean levels of dicentrics and total unstable aberrations began to decline when fractions were delivered with intervals of greater than 2 h. With 200 rad the yield had decreased to an additive baseline (i.e. equal to only twice the yield of a single 100-rad fraction) by an interval of 4 h. Following 500 rad the yield declined until 8 h and then remained 20% above the additive baseline even when 48 h separated the fractions. Possible explanations for this discrepancy are discussed. In a second experiment PHA stimulated lymphocyte cultures were exposed to 2 doses of 125 rad of X-rays up to 7 h apart in an attempt to demonstrate the late peak in aberration yields originally reported by Lane [5]. Control cultures received unsplit doses of 250 rad at the time of the corresponding second 125-rad fraction. No evidence of a late peak in dicentric yield was observed. The yield remained approximately the same irrespective of the time interval between fractions but these split dose yields were significantly different from the accompanying unsplit controls."} {"id": "PMID:1264110", "title": "X-ray-induced mutants resistant to 8-azaguanine. I. Effects of cell density and expression time.", "content": "Asynchronous Chinese hamster ovary cells were irradiated and colony survival in Alpha MEM medium with dialyzed serum was determined with or without 15 mug/ml 8-Azaguanine (AG). Data indicated that a reproducible assay for the system was dependent upon controlling cell density at least two days prior to induction as well as throughout the expression period. Generally, spontaneous and radiation-induced mutant frequencies decreased when cell densities exceeded a critical density of 3-6 X 10(4) cells/cm2. Infrequently, the critical density was exceeded by a factor of two with no observed decrease, possibly correlated with a longer cell doubling time. Drug depletion artifacts can occur because of drug degradation, or because wild-type cells utilize the drug or produce conditions which reduce uptake of the drug. Thus, as the effective drug concentration is lowered, the observed mutant frequency increases because a spectrum of mutants resistant to only low concentrations can now survive. In fact, refeeding with AG at intervals during the incubation period lowered spontaneous and radiation-induced frequencies approx. 5-fold. Therefore, to standardize conditions, cells were trypsinized at the end of the expression time and replated at a constant cell number for mutant selection by AG. Over two generations of growth during the expression period were required for optimal manifestation of induced mutants, and when densities were kept below 4 X 10(4) cells/cm2 at all times, observed mutant frequencies did not change significantly over a period between 80 and 140 h post-induction (over 4 generations for irradiated cells and over 6 generations for controls). Previous reports of observed mutant frequencies decreasing beyond three generations may be due to cell interaction prior to mutant selection.", "contents": "X-ray-induced mutants resistant to 8-azaguanine. I. Effects of cell density and expression time. Asynchronous Chinese hamster ovary cells were irradiated and colony survival in Alpha MEM medium with dialyzed serum was determined with or without 15 mug/ml 8-Azaguanine (AG). Data indicated that a reproducible assay for the system was dependent upon controlling cell density at least two days prior to induction as well as throughout the expression period. Generally, spontaneous and radiation-induced mutant frequencies decreased when cell densities exceeded a critical density of 3-6 X 10(4) cells/cm2. Infrequently, the critical density was exceeded by a factor of two with no observed decrease, possibly correlated with a longer cell doubling time. Drug depletion artifacts can occur because of drug degradation, or because wild-type cells utilize the drug or produce conditions which reduce uptake of the drug. Thus, as the effective drug concentration is lowered, the observed mutant frequency increases because a spectrum of mutants resistant to only low concentrations can now survive. In fact, refeeding with AG at intervals during the incubation period lowered spontaneous and radiation-induced frequencies approx. 5-fold. Therefore, to standardize conditions, cells were trypsinized at the end of the expression time and replated at a constant cell number for mutant selection by AG. Over two generations of growth during the expression period were required for optimal manifestation of induced mutants, and when densities were kept below 4 X 10(4) cells/cm2 at all times, observed mutant frequencies did not change significantly over a period between 80 and 140 h post-induction (over 4 generations for irradiated cells and over 6 generations for controls). Previous reports of observed mutant frequencies decreasing beyond three generations may be due to cell interaction prior to mutant selection."} {"id": "PMID:1264111", "title": "X-ray-induced mutants resistant to 8-azaguanine. II. Cell cycle dose response.", "content": "Synchronous Chinese hamster ovary cells were irradiated in G1 or S phase. Colony survival in Alpha MEM medium with dialyzed serum was determined with or without 15 mug/ml 8-azaguanine (AG). An expression period of over three generations (multiplicity of 20) was utilized, with expression times ranging from 58 to 114 h. Both G1 and S phase were practically identical in sensitivity to X-ray-induced mutations, with mutant frequency/viable cell/rad ranging from 1 X 10(-7) (75-100 rad) to 8 X 10(-7) (1000 rad). The spontaneous mutation rate, shown by Luria-Delbruck fluctuation analysis, was 5 X 10(-7) per generation. Thirty-three mutants, isolated at random and grown for over 30 generations in the absence of AG, were analyzed for plating efficiency (PE) in different concentrations of AG or in hypoxanthine-aminopterin-thymidine (HAT) medium. Of these, 64% were resistant (PE greater than 0.1) to 7.5 mug/ml AG, 85% to 5.0 mug/ml, and 91% to 3.5 mug/ml. Only 42% showed possible hypoxanthine-phosphoribosyltransferase (hprtase) deficiency as evidenced by HAT sensitivity (PE less than 0.1). Wild type controls exhibited PE's in 3.5 mug/ml AG of less than 0.001 and in HAT of greater than 0.5. Of ten mutants studied, all demonstrated survival response to radiation similar to wild type cells (D0 of approx. 120 rad). For radiation protection standards, the radiation dose required to induce mutations at a rate equal to that occurring spontaneously is called the doubling dose. The doubling dose observed for acute irradiation was about 3 rad and was estimated to be 10-60 rad for chronic irradiation, similar to that often reported for in vivo studies.", "contents": "X-ray-induced mutants resistant to 8-azaguanine. II. Cell cycle dose response. Synchronous Chinese hamster ovary cells were irradiated in G1 or S phase. Colony survival in Alpha MEM medium with dialyzed serum was determined with or without 15 mug/ml 8-azaguanine (AG). An expression period of over three generations (multiplicity of 20) was utilized, with expression times ranging from 58 to 114 h. Both G1 and S phase were practically identical in sensitivity to X-ray-induced mutations, with mutant frequency/viable cell/rad ranging from 1 X 10(-7) (75-100 rad) to 8 X 10(-7) (1000 rad). The spontaneous mutation rate, shown by Luria-Delbruck fluctuation analysis, was 5 X 10(-7) per generation. Thirty-three mutants, isolated at random and grown for over 30 generations in the absence of AG, were analyzed for plating efficiency (PE) in different concentrations of AG or in hypoxanthine-aminopterin-thymidine (HAT) medium. Of these, 64% were resistant (PE greater than 0.1) to 7.5 mug/ml AG, 85% to 5.0 mug/ml, and 91% to 3.5 mug/ml. Only 42% showed possible hypoxanthine-phosphoribosyltransferase (hprtase) deficiency as evidenced by HAT sensitivity (PE less than 0.1). Wild type controls exhibited PE's in 3.5 mug/ml AG of less than 0.001 and in HAT of greater than 0.5. Of ten mutants studied, all demonstrated survival response to radiation similar to wild type cells (D0 of approx. 120 rad). For radiation protection standards, the radiation dose required to induce mutations at a rate equal to that occurring spontaneously is called the doubling dose. The doubling dose observed for acute irradiation was about 3 rad and was estimated to be 10-60 rad for chronic irradiation, similar to that often reported for in vivo studies."} {"id": "PMID:1264112", "title": "Ethyl methanesulphonate mutagenesis with L5178Y mouse lymphoma cells: a comparison of ouabain, thioguanine and excess thymidine resistance.", "content": "Complete inhibition of growth of sensitive L5178Y mouse lymphoma cells in culture was obtained with 10(-3)M ouabain, 1.65 X 10(-3)M thymidine, 1.8 X 10(-4)M thioguanine and 10(-6)M cytosine arabinoside. The toxicity of methotrexate was dependent upon cell density and this compound was excluded from further study. The expression time before addition of the selective agent was important for detecting EMS induced resistant variants. Ouabain-resistant variants appeared immediately after treatment and were present over a broad time span. No excess thymidine- or thioguanine-resistant variants were seen initially; a peak in variant numbers was seen for excess thymidine resistance at 48-96 h and for thioguanine resistance at 144-192 h. Using induced mutation frequencies at optimum expression times, equal EMS treatments yielded substantially more variants resistant to thioguanine than to ouabain. It is suggested that this difference may have origin in possible constraints in the classes of mutants which are permissible in a vital function, maintenance of the Na+/K+ balance, when compared with a non-vital function, salvage purine biosynthesis. Some data are presented on the stability in culture of resistant variants. A limited number of observations were made following treatment in the peritoneal cavity of the mouse which were in broad agreement with the above results.", "contents": "Ethyl methanesulphonate mutagenesis with L5178Y mouse lymphoma cells: a comparison of ouabain, thioguanine and excess thymidine resistance. Complete inhibition of growth of sensitive L5178Y mouse lymphoma cells in culture was obtained with 10(-3)M ouabain, 1.65 X 10(-3)M thymidine, 1.8 X 10(-4)M thioguanine and 10(-6)M cytosine arabinoside. The toxicity of methotrexate was dependent upon cell density and this compound was excluded from further study. The expression time before addition of the selective agent was important for detecting EMS induced resistant variants. Ouabain-resistant variants appeared immediately after treatment and were present over a broad time span. No excess thymidine- or thioguanine-resistant variants were seen initially; a peak in variant numbers was seen for excess thymidine resistance at 48-96 h and for thioguanine resistance at 144-192 h. Using induced mutation frequencies at optimum expression times, equal EMS treatments yielded substantially more variants resistant to thioguanine than to ouabain. It is suggested that this difference may have origin in possible constraints in the classes of mutants which are permissible in a vital function, maintenance of the Na+/K+ balance, when compared with a non-vital function, salvage purine biosynthesis. Some data are presented on the stability in culture of resistant variants. A limited number of observations were made following treatment in the peritoneal cavity of the mouse which were in broad agreement with the above results."} {"id": "PMID:1264114", "title": "Effects of childhood leukemia and chemotherapy on puberty and reproductive function in girls.", "content": "Longer survivial in childhood leukemia prompted this study of pubertal development and reproductive function in 35 girls and women. Twenty-eight patients (80 per cent) had normal pubertal progression during a median of 74 months after diagnosis of leukemia and 49 months of chemotherapy. Seven patients were abnormal: four exhibited hypothalamic-pituitary dysfunction with suppression of circulating serum gonadotropins (less than 6 mlU per milliliter); three others had evidence of primary ovarian dysfunction - reversible in two - with inappropriately elevated circulating serum gonadotropins (follicle-stimulating hormone greater than 20 mlU per milliliter). Normal sexual development correlated best with pubertal status at onset of leukemia; only one of 17 patients with diagnosis before puberty experienced altered pubertal progression, whereas abnormalities appeared in six of 18 with onset during puberty or after menarche. Thus, most girls with aggressively treated child-hood leukemia have an excellent prognosis for normal hypothalamic-pituitary-ovarian function; normal development is further enhanced in patients who are prepubertal at onset of leukemia.", "contents": "Effects of childhood leukemia and chemotherapy on puberty and reproductive function in girls. Longer survivial in childhood leukemia prompted this study of pubertal development and reproductive function in 35 girls and women. Twenty-eight patients (80 per cent) had normal pubertal progression during a median of 74 months after diagnosis of leukemia and 49 months of chemotherapy. Seven patients were abnormal: four exhibited hypothalamic-pituitary dysfunction with suppression of circulating serum gonadotropins (less than 6 mlU per milliliter); three others had evidence of primary ovarian dysfunction - reversible in two - with inappropriately elevated circulating serum gonadotropins (follicle-stimulating hormone greater than 20 mlU per milliliter). Normal sexual development correlated best with pubertal status at onset of leukemia; only one of 17 patients with diagnosis before puberty experienced altered pubertal progression, whereas abnormalities appeared in six of 18 with onset during puberty or after menarche. Thus, most girls with aggressively treated child-hood leukemia have an excellent prognosis for normal hypothalamic-pituitary-ovarian function; normal development is further enhanced in patients who are prepubertal at onset of leukemia."} {"id": "PMID:1264115", "title": "Gallbladder disease. Prevalence in a South Wales industrial town.", "content": "In a weighted random sample of the specially enumerated population of a South Wales industrial town, examined by cholecystography for gallstones, the overall prevalence rates were 6.2 per cent for men 45 to 69 years of age and 12.1 per cent for women of the same ages. Contrary to our expectation there was no marked increase in prevalence with age in either sex. Symptoms of dyspepsia said to be suggestive of gallstones were found with approximately equal frequency in those with and without gallbladder disease.", "contents": "Gallbladder disease. Prevalence in a South Wales industrial town. In a weighted random sample of the specially enumerated population of a South Wales industrial town, examined by cholecystography for gallstones, the overall prevalence rates were 6.2 per cent for men 45 to 69 years of age and 12.1 per cent for women of the same ages. Contrary to our expectation there was no marked increase in prevalence with age in either sex. Symptoms of dyspepsia said to be suggestive of gallstones were found with approximately equal frequency in those with and without gallbladder disease."} {"id": "PMID:1264135", "title": "Correction of the permeability defect in hereditary stomatocytosis by dimethyl adipimidate.", "content": "The effect of imidoesters on the extraordinarily increased cation permeability of hereditary stomatocytes was evaluated in erythrocytes from a splenectomized boy with persistent hemolytic anemia. Reaction of stomatocytes with dimethyl adipimidate reduced ouabain-associated potassium loss from 15 to 1.7 and sodium gain from 22 to 2.5 meq per liter of red cells per hours. Red-cell volume, cation concentration, and deformability, previously abnormal, rapidly became normal after stomatocytes were reacted with dimethyl adipimidate. Instead of stomatocytes, normal red cells and target cells were noted. The survival (half-time) of stomatocytes treated with 51Cr-labeled dimethyl adipimidate infused into rats rendered tolerant to human erythorocytes by pretreatment with ethyl palmitate and cobra-venom factor was double that of untreated stomatocytes. Chemical modification of the defect in vitro allowed stomatocytes to regain many properites of normal erythrocytes and favorably influenced the subsequent survival of these cells in vivo.", "contents": "Correction of the permeability defect in hereditary stomatocytosis by dimethyl adipimidate. The effect of imidoesters on the extraordinarily increased cation permeability of hereditary stomatocytes was evaluated in erythrocytes from a splenectomized boy with persistent hemolytic anemia. Reaction of stomatocytes with dimethyl adipimidate reduced ouabain-associated potassium loss from 15 to 1.7 and sodium gain from 22 to 2.5 meq per liter of red cells per hours. Red-cell volume, cation concentration, and deformability, previously abnormal, rapidly became normal after stomatocytes were reacted with dimethyl adipimidate. Instead of stomatocytes, normal red cells and target cells were noted. The survival (half-time) of stomatocytes treated with 51Cr-labeled dimethyl adipimidate infused into rats rendered tolerant to human erythorocytes by pretreatment with ethyl palmitate and cobra-venom factor was double that of untreated stomatocytes. Chemical modification of the defect in vitro allowed stomatocytes to regain many properites of normal erythrocytes and favorably influenced the subsequent survival of these cells in vivo."} {"id": "PMID:1264136", "title": "Research, the lifeline of medicine.", "content": "Advances in medicine spring from discoveries in physics, chemistry and biology. Among key contributions to the diagnosis, treatment and prevention of cardiovascular and pulmonary diseases, a recent Comroe-Dripps analysis shows two thirds to have been basic rather than applied research. Without a firm foundation in basic knowledge innovations perceived as advances prove hollow and collapse. Strong social, economic and political pressures now threaten acquisition of basic knowledge. Scientists feel driven to undertake excessively complex problems and gamble against the historical record that science generally progresses by tackling discrete and well defined questions. Regardless of circumstances, professional standards require the physician and scientist to be creative and enlarge the fund of knowledge.", "contents": "Research, the lifeline of medicine. Advances in medicine spring from discoveries in physics, chemistry and biology. Among key contributions to the diagnosis, treatment and prevention of cardiovascular and pulmonary diseases, a recent Comroe-Dripps analysis shows two thirds to have been basic rather than applied research. Without a firm foundation in basic knowledge innovations perceived as advances prove hollow and collapse. Strong social, economic and political pressures now threaten acquisition of basic knowledge. Scientists feel driven to undertake excessively complex problems and gamble against the historical record that science generally progresses by tackling discrete and well defined questions. Regardless of circumstances, professional standards require the physician and scientist to be creative and enlarge the fund of knowledge."} {"id": "PMID:1264151", "title": "Increasing incidence of endometrial cancer in the United States.", "content": "Data from eight areas in the United States served by population-based cancer reporting systems indicate that, after many years of relative stability, incidence rates of endometrial cancer have risen sharply in the 1970's. In some areas the amount of the increase has exceeded 10 per cent per year. The incidence among middle-aged women has changed most (by 40 to 150 per cent between 1969 and 1973, depending on the area), but rates have increased in younger women and the elderly as well.", "contents": "Increasing incidence of endometrial cancer in the United States. Data from eight areas in the United States served by population-based cancer reporting systems indicate that, after many years of relative stability, incidence rates of endometrial cancer have risen sharply in the 1970's. In some areas the amount of the increase has exceeded 10 per cent per year. The incidence among middle-aged women has changed most (by 40 to 150 per cent between 1969 and 1973, depending on the area), but rates have increased in younger women and the elderly as well."} {"id": "PMID:1264152", "title": "Sweden's no-fault patient-injury insurance.", "content": "Sweden has introduced a nationwide nofault patient-injury compensation plan. The plan was not introduced because malpractice insurance costs were high, but because so few injured patients received compensation through the tort liability system. With certain exceptions, compensation is provided for loss that occurs as a result of injury related to hospitalization or medical care. The insurance plan has completed 12 months of operation. It total cost is less than 50 cents per citizen, and it is financed from general tax revenue. Sweden's experience can be projected to a population the size of the United States, and the results compared to United States malpractice liability figures. Such a comparison indicates a total number of awards greater than that of the United States, but a lower average amount per award.", "contents": "Sweden's no-fault patient-injury insurance. Sweden has introduced a nationwide nofault patient-injury compensation plan. The plan was not introduced because malpractice insurance costs were high, but because so few injured patients received compensation through the tort liability system. With certain exceptions, compensation is provided for loss that occurs as a result of injury related to hospitalization or medical care. The insurance plan has completed 12 months of operation. It total cost is less than 50 cents per citizen, and it is financed from general tax revenue. Sweden's experience can be projected to a population the size of the United States, and the results compared to United States malpractice liability figures. Such a comparison indicates a total number of awards greater than that of the United States, but a lower average amount per award."} {"id": "PMID:1264176", "title": "Progress toward a National Blood System. The American Blood Commission.", "content": "The success of the American Blood Commission in improving the effectiveness and efficiency of blood service delivery in the United States depends on the Commission's interactions with its members, with HEW and with the Congress. Active involvement of over 36 national organizations as dues-paying members representing both consumer/donors and providers gives the Commission considerable influence. HEW underwrites specific programs of the Commission and HEW agencies display co-operation and re-enforcement of its moves. The Congress has refrained from actions that might undercut the effort. An all-voluntary blood-donor system is a key American Blood Commission objective. The argument for voluntarism is supported by the need to control hepatitis, but other means of controlling hepatitis may be developed. The Commission's plan for a national blood system is based on securing voluntary compliance with guidelines recommended by peer groups within the Commission, and should facilitate a more effective national blood-transfusion system.", "contents": "Progress toward a National Blood System. The American Blood Commission. The success of the American Blood Commission in improving the effectiveness and efficiency of blood service delivery in the United States depends on the Commission's interactions with its members, with HEW and with the Congress. Active involvement of over 36 national organizations as dues-paying members representing both consumer/donors and providers gives the Commission considerable influence. HEW underwrites specific programs of the Commission and HEW agencies display co-operation and re-enforcement of its moves. The Congress has refrained from actions that might undercut the effort. An all-voluntary blood-donor system is a key American Blood Commission objective. The argument for voluntarism is supported by the need to control hepatitis, but other means of controlling hepatitis may be developed. The Commission's plan for a national blood system is based on securing voluntary compliance with guidelines recommended by peer groups within the Commission, and should facilitate a more effective national blood-transfusion system."} {"id": "PMID:1264187", "title": "Suppression of malignancy in human cells.", "content": "Fusion between malignant and normal human cells results in the suppression of malignancy as measured by tumour formation. Malignant-malignant hybrids retain their malignant character. The human cell system has advantages for the study of the control of malignancy.", "contents": "Suppression of malignancy in human cells. Fusion between malignant and normal human cells results in the suppression of malignancy as measured by tumour formation. Malignant-malignant hybrids retain their malignant character. The human cell system has advantages for the study of the control of malignancy."} {"id": "PMID:1264202", "title": "Genomic transcriptional activity and the structure of chromatin.", "content": "Nucleic acid hybridisation has shown that micrococcal nuclease-derived chromatin subunits from the cells of Xenopus laevis contain fragments of ribosomal 28S, 18S and 5S RNAS within the population of 200 base-pair pieces of DNA. Subunits from cultured embryonic cells actively transcribing ribosomal RNA contain only 70-74% of the cistrons present in undigested wild-type DNA, while subunits from adult erythrocytes not active in RNA transcription contain close to 90% of the ribosomal cistrons in native chromatin.", "contents": "Genomic transcriptional activity and the structure of chromatin. Nucleic acid hybridisation has shown that micrococcal nuclease-derived chromatin subunits from the cells of Xenopus laevis contain fragments of ribosomal 28S, 18S and 5S RNAS within the population of 200 base-pair pieces of DNA. Subunits from cultured embryonic cells actively transcribing ribosomal RNA contain only 70-74% of the cistrons present in undigested wild-type DNA, while subunits from adult erythrocytes not active in RNA transcription contain close to 90% of the ribosomal cistrons in native chromatin."} {"id": "PMID:1264203", "title": "Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene.", "content": "Bacteriophage MS2 RNA is 3,569 nucleotides long. The nucleotide sequence has been established for the third and last gene, which codes for the replicase protein. A secondary structure model has also been proposed. Biological properties, such as ribosome binding and codon interactions can now be discussed on a molecular basis. As the sequences for the other regions of this RNA have been published already, the complete, primary chemical structure of a viral genome has now been established.", "contents": "Complete nucleotide sequence of bacteriophage MS2 RNA: primary and secondary structure of the replicase gene. Bacteriophage MS2 RNA is 3,569 nucleotides long. The nucleotide sequence has been established for the third and last gene, which codes for the replicase protein. A secondary structure model has also been proposed. Biological properties, such as ribosome binding and codon interactions can now be discussed on a molecular basis. As the sequences for the other regions of this RNA have been published already, the complete, primary chemical structure of a viral genome has now been established."} {"id": "PMID:1264220", "title": "Genetic hypertension in rats is accompanied by a defect in renal prostaglandin catabolism.", "content": "Noradrenaline releases prostaglandins in the kidney, and in rats these augment rather than reduce vasoconstriction produced by the amine. Homogenates of kidneys of New Zealand rats inbred for hypertension exhibit lower prostaglandin inactivation by 15-hydroxydehydrogenase than controls. At the same time, augmentation of noradrenaline vasoconstriction by the released prostaglandin is exaggerated. This biochemical defect could be the inherited abnormality primarily responsible for the development of hypertension in these animals.", "contents": "Genetic hypertension in rats is accompanied by a defect in renal prostaglandin catabolism. Noradrenaline releases prostaglandins in the kidney, and in rats these augment rather than reduce vasoconstriction produced by the amine. Homogenates of kidneys of New Zealand rats inbred for hypertension exhibit lower prostaglandin inactivation by 15-hydroxydehydrogenase than controls. At the same time, augmentation of noradrenaline vasoconstriction by the released prostaglandin is exaggerated. This biochemical defect could be the inherited abnormality primarily responsible for the development of hypertension in these animals."} {"id": "PMID:1264239", "title": "Bicycle-pedal model for the first step in the vision process.", "content": "Computer simulation of the molecular dynamics of retinal during its photoisomerisation inside a restrictive active site gives a detailed model for the sequence of events in the first step of the vision process. It is proposed that the prelumirhodopsin intermediate contains a strained all-trans retinal molecule produced directly and rapidly from the 11-cis, 12-s-trans conformation in rhodopsin by a bicycle-pedal isomerisation. The model reproduces the main experimental observations and explains how the protein makes the photoisomerisation path unique.", "contents": "Bicycle-pedal model for the first step in the vision process. Computer simulation of the molecular dynamics of retinal during its photoisomerisation inside a restrictive active site gives a detailed model for the sequence of events in the first step of the vision process. It is proposed that the prelumirhodopsin intermediate contains a strained all-trans retinal molecule produced directly and rapidly from the 11-cis, 12-s-trans conformation in rhodopsin by a bicycle-pedal isomerisation. The model reproduces the main experimental observations and explains how the protein makes the photoisomerisation path unique."} {"id": "PMID:1264250", "title": "Messenger RNA for the coat protein of tobacco mosaic virus.", "content": "TMV RNA is not an efficient template for translation of the viral coat protein, in spite of containing nucleotide sequences coding for the protein. Efficient translation requires the prior synthesis within infected cells of a smaller RNA carrying only a portion of the information encoded in the whole genome.", "contents": "Messenger RNA for the coat protein of tobacco mosaic virus. TMV RNA is not an efficient template for translation of the viral coat protein, in spite of containing nucleotide sequences coding for the protein. Efficient translation requires the prior synthesis within infected cells of a smaller RNA carrying only a portion of the information encoded in the whole genome."} {"id": "PMID:1264263", "title": "Nomograms for obtaining a necessary, minimum sample size. I. When distribution of data is normal.", "content": "Four different nomograms were devised to obtain a necessary, minimum sample size at a 95% confidence rate when data were distributed normally. They corresponded to four different cases, the population of which was either infinite or finite and the permitted error of which was either mu--m or mu--m/s, where mu was population mean, m sample mean and s sample standard deviation. They could also be used for obtaining the confidence limits of the population mean from the data after having carried out a work.", "contents": "Nomograms for obtaining a necessary, minimum sample size. I. When distribution of data is normal. Four different nomograms were devised to obtain a necessary, minimum sample size at a 95% confidence rate when data were distributed normally. They corresponded to four different cases, the population of which was either infinite or finite and the permitted error of which was either mu--m or mu--m/s, where mu was population mean, m sample mean and s sample standard deviation. They could also be used for obtaining the confidence limits of the population mean from the data after having carried out a work."} {"id": "PMID:1264287", "title": "[A histochemical study of acetylcholinesterase in intact and deafferented cat auditory cortex].", "content": "The peculiarities of the AChE distribution were investigated in the intact cat auditory cortex and during early period of its neuronal isolation. It is shown that in the isolated cortex slab the staining of the AChE containing fibre disappeared from the neuropile, while in the intact cortex it was well pronounced. AChE accumulation was observed in the proximal parts of the transsected thalamo-cortical fibres. It is supposed that the AChE-containing fibres in the auditory cortex belong to nonspecific thalamic inputs.", "contents": "[A histochemical study of acetylcholinesterase in intact and deafferented cat auditory cortex]. The peculiarities of the AChE distribution were investigated in the intact cat auditory cortex and during early period of its neuronal isolation. It is shown that in the isolated cortex slab the staining of the AChE containing fibre disappeared from the neuropile, while in the intact cortex it was well pronounced. AChE accumulation was observed in the proximal parts of the transsected thalamo-cortical fibres. It is supposed that the AChE-containing fibres in the auditory cortex belong to nonspecific thalamic inputs."} {"id": "PMID:1264288", "title": "[Comparative characteristics of the background activity of neurons from several regions of the cerebral cortex of unanesthetized cats].", "content": "Neuronal background activity in associative (area 5) and certain projection regions (SI, AI, AII) of the cerebral cortex was studied in curarized cats. Different types of the neuronal activitke intervals distribution and autocorrelation function. All these statistical parameters indicated that the background activity of associative neurons significantly differed from that of projective field neurons. Bursts generation was the main peculiarity of the background activity of auditory cortical neurons. According to all the parameters studied the level of the background activity in the somatic sensory cortex was lower. The probable functional significance of these differences is discussed.", "contents": "[Comparative characteristics of the background activity of neurons from several regions of the cerebral cortex of unanesthetized cats]. Neuronal background activity in associative (area 5) and certain projection regions (SI, AI, AII) of the cerebral cortex was studied in curarized cats. Different types of the neuronal activitke intervals distribution and autocorrelation function. All these statistical parameters indicated that the background activity of associative neurons significantly differed from that of projective field neurons. Bursts generation was the main peculiarity of the background activity of auditory cortical neurons. According to all the parameters studied the level of the background activity in the somatic sensory cortex was lower. The probable functional significance of these differences is discussed."} {"id": "PMID:1264289", "title": "[Changes in the postsynaptic and spike potentials of a cortical neuron during habituation].", "content": "Changes in the spikes, EPSPs and IPSPs of neurons in the general cortex of the turtle forebrain were studied intracellularly during irregular repetition of light flasches. The amplitudes of these intracellular potentials decreased during habituation without any change in the resting potential. Their dependence on the membrane potential level changed. The short-latent evoked spikes decreased more considerably as compared with the spontaneous spikes and the spikes after IPSP. Probably, the decrease of the spontaneous spike and the spike after the IPSP reflects a nonspecific decrease in the excitability of a neuron because of the long intracellular recording so far as during extracellularly recording only the short-latent evoked spike decreased with habituation. The decrease of the short-latent evoked spike reflects neuronal habituation. A disinhibition of spikes and PSPs was observed. A suggestion is advanced that the pattern of synapses activated by a definite repetitive stimulus evokes a transitory change of the electrogenic properties of the neuronal membrane.", "contents": "[Changes in the postsynaptic and spike potentials of a cortical neuron during habituation]. Changes in the spikes, EPSPs and IPSPs of neurons in the general cortex of the turtle forebrain were studied intracellularly during irregular repetition of light flasches. The amplitudes of these intracellular potentials decreased during habituation without any change in the resting potential. Their dependence on the membrane potential level changed. The short-latent evoked spikes decreased more considerably as compared with the spontaneous spikes and the spikes after IPSP. Probably, the decrease of the spontaneous spike and the spike after the IPSP reflects a nonspecific decrease in the excitability of a neuron because of the long intracellular recording so far as during extracellularly recording only the short-latent evoked spike decreased with habituation. The decrease of the short-latent evoked spike reflects neuronal habituation. A disinhibition of spikes and PSPs was observed. A suggestion is advanced that the pattern of synapses activated by a definite repetitive stimulus evokes a transitory change of the electrogenic properties of the neuronal membrane."} {"id": "PMID:1264290", "title": "[Characteristics of the reactions of bat superior olivary neurons to single and paired ultrasonic stimuli].", "content": "Characteristics of single-unit activity in the superior olivary complex of Rhinolophus ferrum-equinum in response to ultrasonic stimuli with a pulse frequency within the echolocation range were studied. Some neurons were found to have three separate response areas with characteristic frequencies corresponding to one half and one third of the basic frequency ranging from 80 to 86 kHz. When the intensity of stimulus with a pulse frequency equal to the characteristic neuron frequency increased, the tonic response changed into phasic activity. With the use of two overlapping stimuli a change from phasic to tonic response occurred. The frequency of tonic discharge corresponded precisely to that of beats up to 2000 Hz (synchronism of neuronal discharges with each beat cycle). Synchtonized tonic activity persisted under specific pulse frequencies and stimulus intensities.", "contents": "[Characteristics of the reactions of bat superior olivary neurons to single and paired ultrasonic stimuli]. Characteristics of single-unit activity in the superior olivary complex of Rhinolophus ferrum-equinum in response to ultrasonic stimuli with a pulse frequency within the echolocation range were studied. Some neurons were found to have three separate response areas with characteristic frequencies corresponding to one half and one third of the basic frequency ranging from 80 to 86 kHz. When the intensity of stimulus with a pulse frequency equal to the characteristic neuron frequency increased, the tonic response changed into phasic activity. With the use of two overlapping stimuli a change from phasic to tonic response occurred. The frequency of tonic discharge corresponded precisely to that of beats up to 2000 Hz (synchronism of neuronal discharges with each beat cycle). Synchtonized tonic activity persisted under specific pulse frequencies and stimulus intensities."} {"id": "PMID:1264291", "title": "[Evoked potentials in the optic tectum of the carp brain upon electric stimulation of the facial nerve].", "content": "The evoked potentials in the carp tectum opticum in response to stimulation of the afferent pathway for chemical nonolfactory reception, the facial nerve, are positive deflections of 5-25 ms latency which do not reverse during microelectrode submersion. According to the evoked potential amplitude and latent period 7 active zones were distingnished in the ipsilateral tectum differing from each other either in one or in both parameters. The dependence of the response evoked by facial nerve stimulation in the tectum opticum on the impulsation from the medulla is proved by the difference in latency and by disappearance of the response in the tectum while persisting in the medulla after disconnection of both areas of the brain. The existence of efferent influences from the tectum upon the primary centre is suggested as the tectum ablation causes in some parts of the medulla either complete disappearance of the facial evoked potentials or changes in their parameters.", "contents": "[Evoked potentials in the optic tectum of the carp brain upon electric stimulation of the facial nerve]. The evoked potentials in the carp tectum opticum in response to stimulation of the afferent pathway for chemical nonolfactory reception, the facial nerve, are positive deflections of 5-25 ms latency which do not reverse during microelectrode submersion. According to the evoked potential amplitude and latent period 7 active zones were distingnished in the ipsilateral tectum differing from each other either in one or in both parameters. The dependence of the response evoked by facial nerve stimulation in the tectum opticum on the impulsation from the medulla is proved by the difference in latency and by disappearance of the response in the tectum while persisting in the medulla after disconnection of both areas of the brain. The existence of efferent influences from the tectum upon the primary centre is suggested as the tectum ablation causes in some parts of the medulla either complete disappearance of the facial evoked potentials or changes in their parameters."} {"id": "PMID:1264292", "title": "[The effect of stimulation of the posterior hypothalamus on the electrical activity of the neocortex in chronically premesencephalic cats].", "content": "Experiments were carried out on 19 adult cats with chronic brain stem transections at the level of the foremost border of the supperior colliculus. High-frequency electric stimulation of the posterior hypothalamus produced in these cats desynchronization of electrical activity in different parts of the neocortex. A predominant influence from the posterior hypothalamus on the electrical activity of frontal lobes was observed. On the basis of the obtained data, it is suggested that the influences from posterior hypothalamus elicit neocortical activation via thalamic nuclei.", "contents": "[The effect of stimulation of the posterior hypothalamus on the electrical activity of the neocortex in chronically premesencephalic cats]. Experiments were carried out on 19 adult cats with chronic brain stem transections at the level of the foremost border of the supperior colliculus. High-frequency electric stimulation of the posterior hypothalamus produced in these cats desynchronization of electrical activity in different parts of the neocortex. A predominant influence from the posterior hypothalamus on the electrical activity of frontal lobes was observed. On the basis of the obtained data, it is suggested that the influences from posterior hypothalamus elicit neocortical activation via thalamic nuclei."} {"id": "PMID:1264294", "title": "[Afferent activity in fine myelinated and unmyelinated nerve fibers of a cutaneous nerve upon mechanical stimulation of cutaneous receptors].", "content": "The activity in fine myelinated and nonmyelinated nerve fibres of a cat cutaneous nerve was analyzed using a collision method and method improving the signal-to-noise ratio in the antidromic action potential neurogram. On the basis of the investigation of conduction velocities, electrical excitation thresholds and responses to mechanical stimulations, the following groupsare distinguished among fine myelinated and nonmyelinated fibres: group A delta1 (30-14m/s) activated mostly under light mechanical stimulation; group A delta2 (14.4.0 m/s) more readily activated by intense mechanical stimulation; group of \"mixed\" fibres containing myelinated and nonmyelinated nerve fibres (4-2 m/s) activated under both kinds of mechanical stimulation; group C1 (2.0-1.0 M/S) ACTIVATED MOSTLY BY LIGHT Mechanical stimulation and group C2 (1.0-0.15 M/S) CONNECTED WITh receptors that require for excitation intense mechanical stimulation.", "contents": "[Afferent activity in fine myelinated and unmyelinated nerve fibers of a cutaneous nerve upon mechanical stimulation of cutaneous receptors]. The activity in fine myelinated and nonmyelinated nerve fibres of a cat cutaneous nerve was analyzed using a collision method and method improving the signal-to-noise ratio in the antidromic action potential neurogram. On the basis of the investigation of conduction velocities, electrical excitation thresholds and responses to mechanical stimulations, the following groupsare distinguished among fine myelinated and nonmyelinated fibres: group A delta1 (30-14m/s) activated mostly under light mechanical stimulation; group A delta2 (14.4.0 m/s) more readily activated by intense mechanical stimulation; group of \"mixed\" fibres containing myelinated and nonmyelinated nerve fibres (4-2 m/s) activated under both kinds of mechanical stimulation; group C1 (2.0-1.0 M/S) ACTIVATED MOSTLY BY LIGHT Mechanical stimulation and group C2 (1.0-0.15 M/S) CONNECTED WITh receptors that require for excitation intense mechanical stimulation."} {"id": "PMID:1264293", "title": "[Reactions of medial geniculate body neurons to stimulation of the auditory cortex].", "content": "Extra- and intracellular responses of pars principalis neurons in the medial geniculate body to stimulation of the first (AI), second (AII) and third (AIII) auditory cortex were studied in experiments on cats immobilized with d-tubocurarine. In geniculate neurons both antidromic (45-50%) and orthodromic (50-55%) reactions occurred in response to the auditory cortex stimulation. The latencies for antidromic and orthodromic responses were 0.3-2.5 ms and 2.0-ms, respectively. Late responses appeared with a latency of 30-200 ms. 63% of neurons responded antidromically to both AII and AI stimulation, that confirms the suggestion on the projection of a considerable number of the geniculate neurons to both auditory zones. Orthodromic responses of geniculate neurons consisted either of 1-2 spikes or a burst of 8-12 spikes with a frequency of 300-600/sec. The bursts are supposed to be the responses of inhibitory geniculate neurons. Intracellular recording showed the following responses: antidromic spikes, EPSP, EPSP-spike, EPSP-spike-IPSP, EPSP-IPSP and initial IPSP. Above 50% of initial IPSPs had the latency of 2.0-4.0 ms. They are supposed to be produced with the participation of intermediate inhibitory neurons located in the medial geniculate body.", "contents": "[Reactions of medial geniculate body neurons to stimulation of the auditory cortex]. Extra- and intracellular responses of pars principalis neurons in the medial geniculate body to stimulation of the first (AI), second (AII) and third (AIII) auditory cortex were studied in experiments on cats immobilized with d-tubocurarine. In geniculate neurons both antidromic (45-50%) and orthodromic (50-55%) reactions occurred in response to the auditory cortex stimulation. The latencies for antidromic and orthodromic responses were 0.3-2.5 ms and 2.0-ms, respectively. Late responses appeared with a latency of 30-200 ms. 63% of neurons responded antidromically to both AII and AI stimulation, that confirms the suggestion on the projection of a considerable number of the geniculate neurons to both auditory zones. Orthodromic responses of geniculate neurons consisted either of 1-2 spikes or a burst of 8-12 spikes with a frequency of 300-600/sec. The bursts are supposed to be the responses of inhibitory geniculate neurons. Intracellular recording showed the following responses: antidromic spikes, EPSP, EPSP-spike, EPSP-spike-IPSP, EPSP-IPSP and initial IPSP. Above 50% of initial IPSPs had the latency of 2.0-4.0 ms. They are supposed to be produced with the participation of intermediate inhibitory neurons located in the medial geniculate body."} {"id": "PMID:1264295", "title": "[Conduction pathways of the solar plexus in dogs].", "content": "The conduction pathways of dog's solar plexus were studied, using the recording of action potentials of the plexus nerves. Greater splanchnic nerves consists of two groups of afferent A-fibres (conduction velocity of 12-15 and 25-56 m/s), afferent C-fibres (conduction velocity of 0.4-2.0 m/s) and preganglionic B- and C-fibres (conduction velocity of 1.0-12.0 m/s). Afferent A- and and C-fibres pass through the solar plexus ganglia to the dorsal roots; preganglionic fibres terminate synaptically on ganglionic neurons, their axons pass in the peripheral nerves to the viscera. Pathways between the peripheral nerves were found; probably they form peripheral reflex arcs.", "contents": "[Conduction pathways of the solar plexus in dogs]. The conduction pathways of dog's solar plexus were studied, using the recording of action potentials of the plexus nerves. Greater splanchnic nerves consists of two groups of afferent A-fibres (conduction velocity of 12-15 and 25-56 m/s), afferent C-fibres (conduction velocity of 0.4-2.0 m/s) and preganglionic B- and C-fibres (conduction velocity of 1.0-12.0 m/s). Afferent A- and and C-fibres pass through the solar plexus ganglia to the dorsal roots; preganglionic fibres terminate synaptically on ganglionic neurons, their axons pass in the peripheral nerves to the viscera. Pathways between the peripheral nerves were found; probably they form peripheral reflex arcs."} {"id": "PMID:1264296", "title": "[The growth of axons in the periphery after a decrease in the quantity of nerve cells in sympathetic ganglia].", "content": "The amount of cells in stellate ganglia of rat was decreased by chemical sympathectomy to 30% of the normal amount. At the age of two months sympathectomized rats have no pressor reflexes to asphyxia and femoral nerve stimulation. These responses are restored at the age of four months. The electron-microscopic and fluorescence-microscopic data show that the growth of axons in the remaining adrenergic neurons of sympathectomized animals takes place at the age between two and four months.", "contents": "[The growth of axons in the periphery after a decrease in the quantity of nerve cells in sympathetic ganglia]. The amount of cells in stellate ganglia of rat was decreased by chemical sympathectomy to 30% of the normal amount. At the age of two months sympathectomized rats have no pressor reflexes to asphyxia and femoral nerve stimulation. These responses are restored at the age of four months. The electron-microscopic and fluorescence-microscopic data show that the growth of axons in the remaining adrenergic neurons of sympathectomized animals takes place at the age between two and four months."} {"id": "PMID:1264297", "title": "[Anatomic correlation between several cortical and subcortical brain structures].", "content": "Investigation of frontal brain sections of 10 cats, 30 dogs and 20 people revealed a topographic correlation between certain cortical and subcortical structures: the beginning of fissura. Sylvii (the so-called \"fossa Sylvii\") and commissura alba cerebri anterior are located always in the same stereotaxic frontal plane. A method of practical application of the revealed topographic correlation is suggested for the stereotaxic operations on higher animals and human beings.", "contents": "[Anatomic correlation between several cortical and subcortical brain structures]. Investigation of frontal brain sections of 10 cats, 30 dogs and 20 people revealed a topographic correlation between certain cortical and subcortical structures: the beginning of fissura. Sylvii (the so-called \"fossa Sylvii\") and commissura alba cerebri anterior are located always in the same stereotaxic frontal plane. A method of practical application of the revealed topographic correlation is suggested for the stereotaxic operations on higher animals and human beings."} {"id": "PMID:1264308", "title": "Renal handling of the third (C3) and fourth (C4) components of the complement system in the nephrotic syndrome.", "content": "Complementuria is a common finding in patients with heavy proteinuria from a variety of causes, and was detected in 23 out of 34 nephrotic subjects. Mean excretion of C3 and C4 in these patients was 49 +/- 22 and 14 +/- 3 mg/24h, respectively. The renal handling of complement appears to be largely molecular weight (MW) dependent, an inverse relationship between the sieving coefficient and MW of transferrin, IgG, C3, and C4 obtaining, in nephrotic patients irrespective of the nature of their glomerulopathy or degree of renal function. Furthermore, glomerular sieving of C3 and C4 was not significantly different in patients with immune glomerular injury associated with extensive glomerular complement deposition, from that in patients with non-immune glomerulopathy, suggesting that no unique mechanism exists for the transglomerular passage of complement from serum into the urine of the former group. The finding of a large increase of sieving of C3 and C4 in nephrotic patients with end-stage renal failure may indicate a failure by atrophic tubules to reabsorb and catabolize filtered complement.", "contents": "Renal handling of the third (C3) and fourth (C4) components of the complement system in the nephrotic syndrome. Complementuria is a common finding in patients with heavy proteinuria from a variety of causes, and was detected in 23 out of 34 nephrotic subjects. Mean excretion of C3 and C4 in these patients was 49 +/- 22 and 14 +/- 3 mg/24h, respectively. The renal handling of complement appears to be largely molecular weight (MW) dependent, an inverse relationship between the sieving coefficient and MW of transferrin, IgG, C3, and C4 obtaining, in nephrotic patients irrespective of the nature of their glomerulopathy or degree of renal function. Furthermore, glomerular sieving of C3 and C4 was not significantly different in patients with immune glomerular injury associated with extensive glomerular complement deposition, from that in patients with non-immune glomerulopathy, suggesting that no unique mechanism exists for the transglomerular passage of complement from serum into the urine of the former group. The finding of a large increase of sieving of C3 and C4 in nephrotic patients with end-stage renal failure may indicate a failure by atrophic tubules to reabsorb and catabolize filtered complement."} {"id": "PMID:1264309", "title": "1alpha-hydroxycholecalciferol. Long-term treatment of patients with uraemic osteodystrophy.", "content": "Three adolescents with uraemic osteodystrophy were treated for 7 months with daily oral doses of 1alpha-hydroxycholecalciferol (0.25-10.0 mug). All the patients were hypocalcaemic and had high serum levels of alkaline phosphatase before the treatment. A rapid rise in serum calcium and a slow, but pronounced decline in serum alkaline phosphatase concentration were observed during the period of treatment. 1alpha-Hydroxycholecalciferol induced hypercalcaemia in two situations. In both cases the hypercalcaemia was transient, serum calcium being normalized in a few days by withdrawal of the drug. Withdrawal of the drug also in other situations resulted in a fall in serum calcium concentration in a couple of days. This suggests that 1alpha-hydroxycholecalciferol should be given daily or every other day. The response did not subside during 7 months of treatment. On the contrary, the maintenance dose necessary to keep serum calcium constant was smaller than the initial dose necessary to normalize serum calcium. Bone mineral content, estimated by photon absorptiometry, rose. The rachitic bone lesions seen radiologically were significantly ameliorated during the treatment.", "contents": "1alpha-hydroxycholecalciferol. Long-term treatment of patients with uraemic osteodystrophy. Three adolescents with uraemic osteodystrophy were treated for 7 months with daily oral doses of 1alpha-hydroxycholecalciferol (0.25-10.0 mug). All the patients were hypocalcaemic and had high serum levels of alkaline phosphatase before the treatment. A rapid rise in serum calcium and a slow, but pronounced decline in serum alkaline phosphatase concentration were observed during the period of treatment. 1alpha-Hydroxycholecalciferol induced hypercalcaemia in two situations. In both cases the hypercalcaemia was transient, serum calcium being normalized in a few days by withdrawal of the drug. Withdrawal of the drug also in other situations resulted in a fall in serum calcium concentration in a couple of days. This suggests that 1alpha-hydroxycholecalciferol should be given daily or every other day. The response did not subside during 7 months of treatment. On the contrary, the maintenance dose necessary to keep serum calcium constant was smaller than the initial dose necessary to normalize serum calcium. Bone mineral content, estimated by photon absorptiometry, rose. The rachitic bone lesions seen radiologically were significantly ameliorated during the treatment."} {"id": "PMID:1264310", "title": "Uremic pericardial effusion. Treatment by catheter drainage and local nonabsorbable steroid administration.", "content": "Pericardial drainage via percutaneous catheter placement and local nonabsorbable steroid instillation was employed as definitive therapy for uremic patients who had intractable pericardial effusions. Twelve patients are reported. Prior daily dialysis, and in one case systemic steroids, were not curative. 11 of 12 cases suffered severe tamponade requiring pericardiocentesis. One patient had an organized pericardial effusion, making pericardiocentesis impossible. He required pericardiectomy with prolonged hospitalization (2 weeks) due to postoperative complications. There were no complications in the 11 patients where catheter drainage and local steroid instillation were employed. No patient had recurrence of his pericardial effusion (followed from 2 weeks to 32 months). Instillation of a relatively nonabsorbable steroid through an indwelling pericardial catheter provides immediate and lasting relief without either the inconvenience or postoperative complications and prolonged hospitalization associated with the surgical procedure of pericardial fenestration. This report offers initial evidence that the percutaneous approach may be a safe and effective alternative to pericardial fenestration in most uremic patients with pericardial effusion.", "contents": "Uremic pericardial effusion. Treatment by catheter drainage and local nonabsorbable steroid administration. Pericardial drainage via percutaneous catheter placement and local nonabsorbable steroid instillation was employed as definitive therapy for uremic patients who had intractable pericardial effusions. Twelve patients are reported. Prior daily dialysis, and in one case systemic steroids, were not curative. 11 of 12 cases suffered severe tamponade requiring pericardiocentesis. One patient had an organized pericardial effusion, making pericardiocentesis impossible. He required pericardiectomy with prolonged hospitalization (2 weeks) due to postoperative complications. There were no complications in the 11 patients where catheter drainage and local steroid instillation were employed. No patient had recurrence of his pericardial effusion (followed from 2 weeks to 32 months). Instillation of a relatively nonabsorbable steroid through an indwelling pericardial catheter provides immediate and lasting relief without either the inconvenience or postoperative complications and prolonged hospitalization associated with the surgical procedure of pericardial fenestration. This report offers initial evidence that the percutaneous approach may be a safe and effective alternative to pericardial fenestration in most uremic patients with pericardial effusion."} {"id": "PMID:1264311", "title": "Increased prevalence of coronary heart disease in analgesic nephropathy: relation to hypertension, hypertriglyceridemia and combined hyperlipidemia.", "content": "The prevalence of coronary heart disease (58%) in 43 patients with analgesic nephropathy with moderate to severe chronic renal failure was significantly higher than in the general population of the same age and sex. Mean serum triglyceride concentration and mean diastolic blood pressure were significantly higher in the group with coronary heart disease (214 mg/dl and 102 mm Hg, respectively) than in the group without it (162 and 94). Serum triglyceride values correlated inversely with GFR, indicating that hypertriglyceridemia was largely due to associated chronic renal failure; a specific effect of analgesic abuse on prevalence of heart disease, noted by others, could not be assessed in the absence of GFR-matched controls. The prevalence of coronary heart disease was significantly higher (81%) in the group with combined hyperlipidemia (hypertriglyceridemia and hypercholesteremia) compared to the groups without it or with normal serum triglyceride concentrations (44 and 41%, respectively). Hypotryptophanemia (a possible cause of hyperlipidemia in the nephrotic syndrome) was present in 77% of patients.", "contents": "Increased prevalence of coronary heart disease in analgesic nephropathy: relation to hypertension, hypertriglyceridemia and combined hyperlipidemia. The prevalence of coronary heart disease (58%) in 43 patients with analgesic nephropathy with moderate to severe chronic renal failure was significantly higher than in the general population of the same age and sex. Mean serum triglyceride concentration and mean diastolic blood pressure were significantly higher in the group with coronary heart disease (214 mg/dl and 102 mm Hg, respectively) than in the group without it (162 and 94). Serum triglyceride values correlated inversely with GFR, indicating that hypertriglyceridemia was largely due to associated chronic renal failure; a specific effect of analgesic abuse on prevalence of heart disease, noted by others, could not be assessed in the absence of GFR-matched controls. The prevalence of coronary heart disease was significantly higher (81%) in the group with combined hyperlipidemia (hypertriglyceridemia and hypercholesteremia) compared to the groups without it or with normal serum triglyceride concentrations (44 and 41%, respectively). Hypotryptophanemia (a possible cause of hyperlipidemia in the nephrotic syndrome) was present in 77% of patients."} {"id": "PMID:1264312", "title": "Glomerular basement membrane antigens in congenital and acquired nephrotic syndrome in childhood.", "content": "Urinary and serum glomerular basement membrane (GBM) antigens were detected by immunodiffusion in patients with nephrotic syndrome and in healthy subjects. The excretion of urinary GBM antigens was greatest in patients with congenital nephrotic syndrome of Finnish type (CNF) and in patients with acquired, therapy-resistant nephrotic syndrome who had a variety of histologically identified glomerular lesions. One GBM antigen, indistinguishable from the urinary one, was also detected in the serum of four of these patients. Excretion of urinary GBM antigens was within normal limits, in patients with steroid-sensitive nephrotic syndrome with minimal changes in renal histology and in the parents (heterozygotes) of CNF patients.", "contents": "Glomerular basement membrane antigens in congenital and acquired nephrotic syndrome in childhood. Urinary and serum glomerular basement membrane (GBM) antigens were detected by immunodiffusion in patients with nephrotic syndrome and in healthy subjects. The excretion of urinary GBM antigens was greatest in patients with congenital nephrotic syndrome of Finnish type (CNF) and in patients with acquired, therapy-resistant nephrotic syndrome who had a variety of histologically identified glomerular lesions. One GBM antigen, indistinguishable from the urinary one, was also detected in the serum of four of these patients. Excretion of urinary GBM antigens was within normal limits, in patients with steroid-sensitive nephrotic syndrome with minimal changes in renal histology and in the parents (heterozygotes) of CNF patients."} {"id": "PMID:1264313", "title": "Multinucleated giant cells in antiglomerular basement membrane antibody-induced glomerulonephritis.", "content": "Inflammatory giant cells were found in close association with glomerular basement membrane in a case of rapidly progressive glomerulonephritis. It is suggested that this finding is due to an alteration in properties of the glomerular basement membrane most probably brought about by circulating antibody to basement membrane.", "contents": "Multinucleated giant cells in antiglomerular basement membrane antibody-induced glomerulonephritis. Inflammatory giant cells were found in close association with glomerular basement membrane in a case of rapidly progressive glomerulonephritis. It is suggested that this finding is due to an alteration in properties of the glomerular basement membrane most probably brought about by circulating antibody to basement membrane."} {"id": "PMID:1264314", "title": "Population genetics of Alport's syndrome. Hypothesis of abnormal segregation and the necessary existence of mutation.", "content": "The diagnosis of Alport's syndrome is generally not considered in the absence of a positive family history. Family studies indicate that transmission occures by a rare autosomal dominant gene. The deviation of transmission ratios from the classical Mendelian pattern is best explained by abnormal segregation. Based on observed pedigree data, calculations were made of the expected equilibrium population frequency of Alport's syndrome assuming mutation rates of zero, 10, and 50 per million gametes. Zero mutation rate should result in disappearance of the Alport gene. An equilibrium frequency corresponding to that actually observed in Rhode Island implies a mutation rate of 10 per million gametes. Furthermore, up to 18% of all newborns with the Alport genotype may represent new mutants. Thus, isolated cases of Alport's syndrome may occur in the absence of other affected family members.", "contents": "Population genetics of Alport's syndrome. Hypothesis of abnormal segregation and the necessary existence of mutation. The diagnosis of Alport's syndrome is generally not considered in the absence of a positive family history. Family studies indicate that transmission occures by a rare autosomal dominant gene. The deviation of transmission ratios from the classical Mendelian pattern is best explained by abnormal segregation. Based on observed pedigree data, calculations were made of the expected equilibrium population frequency of Alport's syndrome assuming mutation rates of zero, 10, and 50 per million gametes. Zero mutation rate should result in disappearance of the Alport gene. An equilibrium frequency corresponding to that actually observed in Rhode Island implies a mutation rate of 10 per million gametes. Furthermore, up to 18% of all newborns with the Alport genotype may represent new mutants. Thus, isolated cases of Alport's syndrome may occur in the absence of other affected family members."} {"id": "PMID:1264315", "title": "Renal arteriolar obstruction without hypertension.", "content": "Selective partial occlusion of the intrarenal arteriolar bed with microspheres in rats resulted in contracted kidneys simulating those of benign nephrosclerosis in man. There was no elevation of blood pressure, renal vein plasma measured by radioimmunoassay, or juxtaglomerular indices of affected kidneys. It is unlikely that arteriolar lesions are pathogenetically related to the development of hypertension.", "contents": "Renal arteriolar obstruction without hypertension. Selective partial occlusion of the intrarenal arteriolar bed with microspheres in rats resulted in contracted kidneys simulating those of benign nephrosclerosis in man. There was no elevation of blood pressure, renal vein plasma measured by radioimmunoassay, or juxtaglomerular indices of affected kidneys. It is unlikely that arteriolar lesions are pathogenetically related to the development of hypertension."} {"id": "PMID:1264316", "title": "Effect of dose on renal diatrizoate concentrations in experimental acute renal failure.", "content": "In rats with glycerol-induced acute renal failure (ARF) and controls, renal concentrations of 125I-labelled sodium diatrizoate were measured 5 min after intravenous doses ranging from 14 to 1,800 mg/kg body weight. Renal concentrations of diatrizoate, at all doses, were much higher in controls than in ARF. A linear relationship existed between dose and renal concentration in ARF. In controls, at doses above 225 mg/kg body weight, the fraction of the dose present in the kidneys diminished and renal iodine content approached that observed in ARF. Differences in diatrizoate concentration which existed between cortical and medullary zones in healthy kidneys at low dises were progressively eliminated as dosage increased, consistent with the osmatic fiutryiv rggrvy of diatrizoate. In ARF, the pattern of intrarenal distribution at all doses was similar to that seen in controls at high doses, though concentrations in outer cortex were consistently slightly higher than those in inner cortex. These observations suggest continuing though reduced, filtration of diatrizoate in ARF by glomeruli already subjected to a large solute load.", "contents": "Effect of dose on renal diatrizoate concentrations in experimental acute renal failure. In rats with glycerol-induced acute renal failure (ARF) and controls, renal concentrations of 125I-labelled sodium diatrizoate were measured 5 min after intravenous doses ranging from 14 to 1,800 mg/kg body weight. Renal concentrations of diatrizoate, at all doses, were much higher in controls than in ARF. A linear relationship existed between dose and renal concentration in ARF. In controls, at doses above 225 mg/kg body weight, the fraction of the dose present in the kidneys diminished and renal iodine content approached that observed in ARF. Differences in diatrizoate concentration which existed between cortical and medullary zones in healthy kidneys at low dises were progressively eliminated as dosage increased, consistent with the osmatic fiutryiv rggrvy of diatrizoate. In ARF, the pattern of intrarenal distribution at all doses was similar to that seen in controls at high doses, though concentrations in outer cortex were consistently slightly higher than those in inner cortex. These observations suggest continuing though reduced, filtration of diatrizoate in ARF by glomeruli already subjected to a large solute load."} {"id": "PMID:1264317", "title": "The effect of plasma calcium on plasma ADH levels in anephric patients.", "content": "Ten anephric patients were studied before and during hemodialysis. The extracorporeal circuit was primed with 5% albumin in 0.9% sodium chloride. Ultrafiltration volume removed by the hemodialyzer was replaced continuously. Modifications of a standard chronic renal failure dialysate were used to minimize changes in plasma urea while varying plasma sodium and calcium in opposite directions. Plasma ionized calcium concentrations in two patients confirmed other studies demonstrating a correlation between plasma total calcium and ionized calcium under these conditions. Plasma ADH determined by bioassay did not correlate with plasma osmolality, plasma sodium concentration, plasma potassium concentration, blood pressure, or pulse rate. The change in plasma ADH during dialysis was significantly correlated only with the change in plasma calcium (r = 0.47, p less than 0.05). The data support the hypothesis that plasma calcium plays a role in the regulation of ADH release in man, independent of the renin-aldosterone system.", "contents": "The effect of plasma calcium on plasma ADH levels in anephric patients. Ten anephric patients were studied before and during hemodialysis. The extracorporeal circuit was primed with 5% albumin in 0.9% sodium chloride. Ultrafiltration volume removed by the hemodialyzer was replaced continuously. Modifications of a standard chronic renal failure dialysate were used to minimize changes in plasma urea while varying plasma sodium and calcium in opposite directions. Plasma ionized calcium concentrations in two patients confirmed other studies demonstrating a correlation between plasma total calcium and ionized calcium under these conditions. Plasma ADH determined by bioassay did not correlate with plasma osmolality, plasma sodium concentration, plasma potassium concentration, blood pressure, or pulse rate. The change in plasma ADH during dialysis was significantly correlated only with the change in plasma calcium (r = 0.47, p less than 0.05). The data support the hypothesis that plasma calcium plays a role in the regulation of ADH release in man, independent of the renin-aldosterone system."} {"id": "PMID:1264321", "title": "Trans-sphenoidal surgical approach in pituitary apoplexy.", "content": "Two cases are described presenting a clinical picture of sudden headache, fever and vomiting, accompanied by unilateral ophthalmoplegia and acute deterioration of visual acuity. In one this amounted to monocular blindness with a field defect in the other, indicative of chiasmal compression. Necrotic pituitary adenoma material was removed by the transphenoidal route in both cases. Recovery of eye movements was obtained and considerable improvement of visual acuity, which in one patient, was restored completely.", "contents": "Trans-sphenoidal surgical approach in pituitary apoplexy. Two cases are described presenting a clinical picture of sudden headache, fever and vomiting, accompanied by unilateral ophthalmoplegia and acute deterioration of visual acuity. In one this amounted to monocular blindness with a field defect in the other, indicative of chiasmal compression. Necrotic pituitary adenoma material was removed by the transphenoidal route in both cases. Recovery of eye movements was obtained and considerable improvement of visual acuity, which in one patient, was restored completely."} {"id": "PMID:1264322", "title": "Cerebral cavernous haemangiomas or cavernomas. Incidence, pathology, localization, diagnosis, clinical features and treatment. Review of the literature and report of an unusual case.", "content": "Reviewing the literature and adding one unusual case the features of 164 cerebral cavernous haemangiomas are described with special reference to incidence, localization, diagnosis and clinical findings. Cavernomas may be found in every age group including the neonatal period. The sex incidence is equal. In 126 cases (76.8%) the cavernomas were of supratentorial, in 34 cases (20.7%) of infratentorial site, and in 4 more cases (2.5%) there was multiple occurence of supratentorial and posterior fossa cavernous haemangiomas. A specific clinical syndrome could not be defined: but the course is usually acute or subacute, and initial symptoms are commonly epileptic fits, acute headache and subarachnoid or intracerebral haemorrhage. Macroscopic calcifications of cerebral cavernomas were found only in 18 cases (11%). Cerebral angiography was done in 31 cases (18.9%). In 9 cases angiography was totally normal, and in 11 cases the cavernoma presented only as an avascular mass. In the remaining cases there was no conformity in the angiographic appearance of cerebral cavernous haemangiomas. Operative extirpation is the treatment of choice if a solitary lesion is favourably located. In addition to our patient there are now 21 cases (12.8%) in which cavernomas were treated successfully by operative extirpation.", "contents": "Cerebral cavernous haemangiomas or cavernomas. Incidence, pathology, localization, diagnosis, clinical features and treatment. Review of the literature and report of an unusual case. Reviewing the literature and adding one unusual case the features of 164 cerebral cavernous haemangiomas are described with special reference to incidence, localization, diagnosis and clinical findings. Cavernomas may be found in every age group including the neonatal period. The sex incidence is equal. In 126 cases (76.8%) the cavernomas were of supratentorial, in 34 cases (20.7%) of infratentorial site, and in 4 more cases (2.5%) there was multiple occurence of supratentorial and posterior fossa cavernous haemangiomas. A specific clinical syndrome could not be defined: but the course is usually acute or subacute, and initial symptoms are commonly epileptic fits, acute headache and subarachnoid or intracerebral haemorrhage. Macroscopic calcifications of cerebral cavernomas were found only in 18 cases (11%). Cerebral angiography was done in 31 cases (18.9%). In 9 cases angiography was totally normal, and in 11 cases the cavernoma presented only as an avascular mass. In the remaining cases there was no conformity in the angiographic appearance of cerebral cavernous haemangiomas. Operative extirpation is the treatment of choice if a solitary lesion is favourably located. In addition to our patient there are now 21 cases (12.8%) in which cavernomas were treated successfully by operative extirpation."} {"id": "PMID:1264324", "title": "[Pain phenomena in amputees. Clinical features, evaluation of tests and possibilities of treatment (author's transl)].", "content": "The clinical phenomena in amputees can be clearly divided into phantom pain, painful stumps and stump pulsation. The various causal mechanisms are described as a basis for the differing assessments of treatment and also compared with our own observations and results.", "contents": "[Pain phenomena in amputees. Clinical features, evaluation of tests and possibilities of treatment (author's transl)]. The clinical phenomena in amputees can be clearly divided into phantom pain, painful stumps and stump pulsation. The various causal mechanisms are described as a basis for the differing assessments of treatment and also compared with our own observations and results."} {"id": "PMID:1264325", "title": "[Cerebral accidents, psychic manifestations, spinocerebellar disturbances and brain tumour (author's transl)].", "content": "At the age of 35 years the patient was affected by epileptic attacks. Two years later psychic changes, vomiting and unsteadiness of gait were noted and not only in the EEG but also in the angiogram, the suspicion of a right hemisphere tumour was expressed. The operation was postponed because the patient's husband was afraid of complications. In the following years other doctors who were concerned with the diagnostic problem, either missed the significance of the existing symptoms or did not attach enough importance to them. As a result of an operation (uterine fibroids) and also because of a slight head injury, an increase in the neurological and psychiatric symptoms was brought about and fortunately this prepared the way for the correct treatment. After the operation there was a significant improvement not only in the psychiatric, but also in the neurological state. As a result of the advanced state of the tumour growth (oligodendroglioma) it was only possible to carry out a sub-total removal. A review of the case indicates that a closer neuropsychiatric and neurosurgical co-operation might have led, at the earliest ten or at the latest five years previously, to a successful outcome of the operation.", "contents": "[Cerebral accidents, psychic manifestations, spinocerebellar disturbances and brain tumour (author's transl)]. At the age of 35 years the patient was affected by epileptic attacks. Two years later psychic changes, vomiting and unsteadiness of gait were noted and not only in the EEG but also in the angiogram, the suspicion of a right hemisphere tumour was expressed. The operation was postponed because the patient's husband was afraid of complications. In the following years other doctors who were concerned with the diagnostic problem, either missed the significance of the existing symptoms or did not attach enough importance to them. As a result of an operation (uterine fibroids) and also because of a slight head injury, an increase in the neurological and psychiatric symptoms was brought about and fortunately this prepared the way for the correct treatment. After the operation there was a significant improvement not only in the psychiatric, but also in the neurological state. As a result of the advanced state of the tumour growth (oligodendroglioma) it was only possible to carry out a sub-total removal. A review of the case indicates that a closer neuropsychiatric and neurosurgical co-operation might have led, at the earliest ten or at the latest five years previously, to a successful outcome of the operation."} {"id": "PMID:1264326", "title": "[Chronic adhesive leptomeningitis of the cauda equina as a cause of ischaemic disturbances (author's transl)].", "content": "An almost typical sciatic syndrome can be occasionally associated with a thickening of the leptomeninges, producing a type of chronic fibroplastic meningitis in the region of the cauda equina. We report here four personal cases, which showed atypical myelographic patterns. The roots of the cauda equina were compressed both by the cystic and by the fibrosing types. In the cases described, the removal of the altered leptomeninges under the operating microscope produced a satisfactory result. A completely symptomfree outcome can rarely be achieved, as the pathological tissue cannot be completely removed.", "contents": "[Chronic adhesive leptomeningitis of the cauda equina as a cause of ischaemic disturbances (author's transl)]. An almost typical sciatic syndrome can be occasionally associated with a thickening of the leptomeninges, producing a type of chronic fibroplastic meningitis in the region of the cauda equina. We report here four personal cases, which showed atypical myelographic patterns. The roots of the cauda equina were compressed both by the cystic and by the fibrosing types. In the cases described, the removal of the altered leptomeninges under the operating microscope produced a satisfactory result. A completely symptomfree outcome can rarely be achieved, as the pathological tissue cannot be completely removed."} {"id": "PMID:1264328", "title": "[Early diagnosis and prevention of severe forms of epilepsy].", "content": "Early diagnosis and treatment are the basis of prevention of severe forms of epilepsy. In order to determine the beginning of the process the author studied 400 cases in which the duration of epilepsy ranged from several weeks to 3 years. The investigations demonstrated that epilepsy develops in subjects presenting certain premorbid symptoms and signs. The \"epileptic process\" develops frequently as a result of past infections and craniocerebral injuries followed by residual neurological signs and cerebrasthenia. Seizure attacks, if no additional releasing factors are present, are preceded by various clinically weakly expressed seizure phenomena. They include peculiar,very vivid dreams, sudden awakenings with partly obnubilated consciouness and a feeling of fear, abortive psychomotor and other seizure. The \"microseizures\" include also myoclonic twitches preceding sleep and during sleep, auras, brief viscerovegatative attacks, opercular symptoms, symptoms of dream-like states, twitches of isolated muscles without consciousness disturbances. In 44% of cases asthenic symptoms were present in connection with microseizures. They served as background for development long-standing irritative foci manifesting themselves clinically with sluggishness of thinking and affect and compulsive features. Presence of these microseizures may suggest epilepsy long before appearance of typical seizures and may be an indication to beginning of treatment which may prevent the development of severe epilepsy. The syndrome of seizure-like microsymptoms makes it possible to recognize the prodromal stage of epilepsy and to change our views on its sudden onset.", "contents": "[Early diagnosis and prevention of severe forms of epilepsy]. Early diagnosis and treatment are the basis of prevention of severe forms of epilepsy. In order to determine the beginning of the process the author studied 400 cases in which the duration of epilepsy ranged from several weeks to 3 years. The investigations demonstrated that epilepsy develops in subjects presenting certain premorbid symptoms and signs. The \"epileptic process\" develops frequently as a result of past infections and craniocerebral injuries followed by residual neurological signs and cerebrasthenia. Seizure attacks, if no additional releasing factors are present, are preceded by various clinically weakly expressed seizure phenomena. They include peculiar,very vivid dreams, sudden awakenings with partly obnubilated consciouness and a feeling of fear, abortive psychomotor and other seizure. The \"microseizures\" include also myoclonic twitches preceding sleep and during sleep, auras, brief viscerovegatative attacks, opercular symptoms, symptoms of dream-like states, twitches of isolated muscles without consciousness disturbances. In 44% of cases asthenic symptoms were present in connection with microseizures. They served as background for development long-standing irritative foci manifesting themselves clinically with sluggishness of thinking and affect and compulsive features. Presence of these microseizures may suggest epilepsy long before appearance of typical seizures and may be an indication to beginning of treatment which may prevent the development of severe epilepsy. The syndrome of seizure-like microsymptoms makes it possible to recognize the prodromal stage of epilepsy and to change our views on its sudden onset."} {"id": "PMID:1264329", "title": "[Possibilities of psychoprophylaxis in epilepsy].", "content": "The psychiatrist should be given also their share in the prevetion of epilepsy by means of raising the psychiatric culture of the society and teaching the population the principles of mental hygiene and psychoprophylaxia. The possibilities of psychiatry in prophylactic management of patients with developed epilepsy include: 1. Energetic measures for controlling attacks which has many psychoprophylactic aspects. 2. Prevention of psychotraumatizing situations leading to secondary neurotic, psychotic and other reactions and behaviour disorders of the type of homilopathy and sociopathy, 3. Counteracting the development of mental and social disability in epileptics. Treatment of epilepsy should be conducted from its very beginning in cooperation with psychiatrists and therapeutic psychologists. The probems of prophylaxis cannot be separated from prophylactic treatment, psychotherapy sociotherapy and rehabilitation.", "contents": "[Possibilities of psychoprophylaxis in epilepsy]. The psychiatrist should be given also their share in the prevetion of epilepsy by means of raising the psychiatric culture of the society and teaching the population the principles of mental hygiene and psychoprophylaxia. The possibilities of psychiatry in prophylactic management of patients with developed epilepsy include: 1. Energetic measures for controlling attacks which has many psychoprophylactic aspects. 2. Prevention of psychotraumatizing situations leading to secondary neurotic, psychotic and other reactions and behaviour disorders of the type of homilopathy and sociopathy, 3. Counteracting the development of mental and social disability in epileptics. Treatment of epilepsy should be conducted from its very beginning in cooperation with psychiatrists and therapeutic psychologists. The probems of prophylaxis cannot be separated from prophylactic treatment, psychotherapy sociotherapy and rehabilitation."} {"id": "PMID:1264331", "title": "E1Intensive therapy and prevention of epilepsy in newborn infants.", "content": "On the basis of an analysis of the material from the Department of Neonatology, Institute of Gynaecology and Obstetrics, Medical Academy in Pozna\u0144 the authors evaluated clinical seizures and their electroencephalographic correlates in the perinatal period. Attention is called to scant clinical symptoms despite frequent seizure activity in EEG. The authors describe the principles of comprehensive treatment in the first days of life.", "contents": "E1Intensive therapy and prevention of epilepsy in newborn infants. On the basis of an analysis of the material from the Department of Neonatology, Institute of Gynaecology and Obstetrics, Medical Academy in Pozna\u0144 the authors evaluated clinical seizures and their electroencephalographic correlates in the perinatal period. Attention is called to scant clinical symptoms despite frequent seizure activity in EEG. The authors describe the principles of comprehensive treatment in the first days of life."} {"id": "PMID:1264332", "title": "[Factors determining favourable or unfavorable results of treatment of epilepsy in children in the light of follow-up observations].", "content": "The described material was divided into two groups. Group I (45,6%) without seizures since 3 years at least, group II (54.4%) with continuing seizures (in 52% of this group the intensity of seizures remained unchanged and in 48% it decreased). The factors determining successful treatment included: unestablished or traumatic aetiology of seizures, partial-simple type of seizures, normal neurological status and normal psychomotor development at the time of onset, small number of seizures prior to beginning of treatment, good effects of drugs. The factors which might determine therapeutic failure included: presence of organic CNS type of seizures (primarily generalized, myoclonic, salaam seizures, and partial secondarily generalized seizures), the dynamics of the disease (frequent refractory seizures), late beginning of treatment. The morphological features of initial EEG tracings in without prognostic significance. In most cases with a favourable course improvement of normalization of EEG tracings was observed, with disappearance of seizure activity followed by regression of focal changes and by normalization of background activity.", "contents": "[Factors determining favourable or unfavorable results of treatment of epilepsy in children in the light of follow-up observations]. The described material was divided into two groups. Group I (45,6%) without seizures since 3 years at least, group II (54.4%) with continuing seizures (in 52% of this group the intensity of seizures remained unchanged and in 48% it decreased). The factors determining successful treatment included: unestablished or traumatic aetiology of seizures, partial-simple type of seizures, normal neurological status and normal psychomotor development at the time of onset, small number of seizures prior to beginning of treatment, good effects of drugs. The factors which might determine therapeutic failure included: presence of organic CNS type of seizures (primarily generalized, myoclonic, salaam seizures, and partial secondarily generalized seizures), the dynamics of the disease (frequent refractory seizures), late beginning of treatment. The morphological features of initial EEG tracings in without prognostic significance. In most cases with a favourable course improvement of normalization of EEG tracings was observed, with disappearance of seizure activity followed by regression of focal changes and by normalization of background activity."} {"id": "PMID:1264334", "title": "[Problem of epileptics not undergoing treatment].", "content": "Among 98 epileptics found in the sample of general population 1/3 were on anticonvulsants when examined, another 1/3 were medicated in the past and a remaining 1/3 never received any medication. Out of 312 samples epileptics known to specialty facilities, 75% were on treatment when examined. Voluntary cessation of medication was frequently observed in both samples of epileptics. Milder epilepsy cases were underrepresented among the patients currently on medication, and significantly more frequent among those who never have been treated or ceased medication on their own. The results of the study show that in some proportion of cases seizures may disappear without treatment, and that prolonged medication may be not the only cause of disappearance of seizures. Moreover, early discontinuation of treatment must not always be followed by recurrence of seizures. Thus, medical prognosis in epilepsy seems to be far better than it has been accepted on the basis of studies on patients known to doctors and medicated for years. Implications of the above results for prevention in epilepsy are discussed briefly.", "contents": "[Problem of epileptics not undergoing treatment]. Among 98 epileptics found in the sample of general population 1/3 were on anticonvulsants when examined, another 1/3 were medicated in the past and a remaining 1/3 never received any medication. Out of 312 samples epileptics known to specialty facilities, 75% were on treatment when examined. Voluntary cessation of medication was frequently observed in both samples of epileptics. Milder epilepsy cases were underrepresented among the patients currently on medication, and significantly more frequent among those who never have been treated or ceased medication on their own. The results of the study show that in some proportion of cases seizures may disappear without treatment, and that prolonged medication may be not the only cause of disappearance of seizures. Moreover, early discontinuation of treatment must not always be followed by recurrence of seizures. Thus, medical prognosis in epilepsy seems to be far better than it has been accepted on the basis of studies on patients known to doctors and medicated for years. Implications of the above results for prevention in epilepsy are discussed briefly."} {"id": "PMID:1264330", "title": "[Causes of epilepsy in children and possibilities of its prevention].", "content": "A seven year follow-up of an unselected group of 1964 children served for establishing the incidence and causes of epilepsy development. The analysis of the health state of the parents, fetal life and birth of this group of patients and a similar analysis of 576 epileptic children treated at the Department of Neurology, Medical Academy in Gda\u0144sk demonstrated a statistically significant correlation between the incidence of epilepsy and the course of pregnancy and labour. It was found that all harmful factors acting on the fetal brain create a specific predisposition to seizure responses of the brain, either spontaneous (epilepsy) or provoked by other factors (e.g. fever induced seizures). Discussing the possibility of epilepsy prevention the author stresses the necessity of reducing the number of pregnancy and labour complications by raising the standard of care of pregnant women and women in labour.", "contents": "[Causes of epilepsy in children and possibilities of its prevention]. A seven year follow-up of an unselected group of 1964 children served for establishing the incidence and causes of epilepsy development. The analysis of the health state of the parents, fetal life and birth of this group of patients and a similar analysis of 576 epileptic children treated at the Department of Neurology, Medical Academy in Gda\u0144sk demonstrated a statistically significant correlation between the incidence of epilepsy and the course of pregnancy and labour. It was found that all harmful factors acting on the fetal brain create a specific predisposition to seizure responses of the brain, either spontaneous (epilepsy) or provoked by other factors (e.g. fever induced seizures). Discussing the possibility of epilepsy prevention the author stresses the necessity of reducing the number of pregnancy and labour complications by raising the standard of care of pregnant women and women in labour."} {"id": "PMID:1264333", "title": "[Analysis of the possibilities of prevention of status epilepticus as well as its complications in children].", "content": "Sixty-five cases of status epilepticus in 51 children were analysed. In 8 cases permanent damage to the CNS resulted and 4 children died. The analysis indicates that the factors influencing the frequency of status epilepticus and CNS damage include: young age of children, infections and their type, withdrawal of antiepileptic medication and the time of beginning treatment of status epilepticus as well as the type of drugs used. In prevention of repeated seizures the authors suggest early administration of anticonvulsants with dehydrating drugs, antipyretics and anti-inflammatory agents. The authors suggest also increasing of the dosage of anticonvulsants in cases of enen common infections beginning in epileptic children.", "contents": "[Analysis of the possibilities of prevention of status epilepticus as well as its complications in children]. Sixty-five cases of status epilepticus in 51 children were analysed. In 8 cases permanent damage to the CNS resulted and 4 children died. The analysis indicates that the factors influencing the frequency of status epilepticus and CNS damage include: young age of children, infections and their type, withdrawal of antiepileptic medication and the time of beginning treatment of status epilepticus as well as the type of drugs used. In prevention of repeated seizures the authors suggest early administration of anticonvulsants with dehydrating drugs, antipyretics and anti-inflammatory agents. The authors suggest also increasing of the dosage of anticonvulsants in cases of enen common infections beginning in epileptic children."} {"id": "PMID:1264336", "title": "[Occupational interests of epileptic children and possibilities of their realization].", "content": "The purpose of this study was an analysis of occupational interests and their relationship to the intellectual capacities of epileptic children. Thirty-three children (20 girls and 13 boys) from the 8th class of elementary school were studied. They had been under treatment for 3 years, at least. The study was performed using the General Classification Test and the Technical Thinking Test. The investigations demonstrated that the girls were interested in humanistic fields while the boys in agriculture and technique. In relation to healthy children the level of occupational aspiration was lower in these children, particularly the boys. The children explained lowering of their occupational aspirations with low intellectual abilities. This motivation has, however, not been confirmed by the results of tests. The authors put forward the hypothesis that lowering aspirations may be also caused by erroneous attitude of the community towards these children.", "contents": "[Occupational interests of epileptic children and possibilities of their realization]. The purpose of this study was an analysis of occupational interests and their relationship to the intellectual capacities of epileptic children. Thirty-three children (20 girls and 13 boys) from the 8th class of elementary school were studied. They had been under treatment for 3 years, at least. The study was performed using the General Classification Test and the Technical Thinking Test. The investigations demonstrated that the girls were interested in humanistic fields while the boys in agriculture and technique. In relation to healthy children the level of occupational aspiration was lower in these children, particularly the boys. The children explained lowering of their occupational aspirations with low intellectual abilities. This motivation has, however, not been confirmed by the results of tests. The authors put forward the hypothesis that lowering aspirations may be also caused by erroneous attitude of the community towards these children."} {"id": "PMID:1264335", "title": "[Resocialization of epileptics in the opinion of psychologists at the Epilepsy Outpatient Clinic in Posna\u0144].", "content": "The investigations were carried out at the Outpatient Epilepsy Clinic in Pozna\u0144 and they were connected with three main problems: family situation, possibility of education, vocational training and work ability of epileptics. The method of programmed clinical history talking with the patient was used and it was supplemented by a talk with a family member. The results of these investigations demonstrated that epileptics after completion of elementary school should be advised to continue education in elementary or secondary vocational schools. In cases of inability to continue work in the acquired occupation the patient should be advised to learn another occupation and only in exceptional cases of application for work disability status should be indicated. In family counseling coexistence of other diseases and the mental status of the patient and possible diseases of the marital partner should be taken into account.", "contents": "[Resocialization of epileptics in the opinion of psychologists at the Epilepsy Outpatient Clinic in Posna\u0144]. The investigations were carried out at the Outpatient Epilepsy Clinic in Pozna\u0144 and they were connected with three main problems: family situation, possibility of education, vocational training and work ability of epileptics. The method of programmed clinical history talking with the patient was used and it was supplemented by a talk with a family member. The results of these investigations demonstrated that epileptics after completion of elementary school should be advised to continue education in elementary or secondary vocational schools. In cases of inability to continue work in the acquired occupation the patient should be advised to learn another occupation and only in exceptional cases of application for work disability status should be indicated. In family counseling coexistence of other diseases and the mental status of the patient and possible diseases of the marital partner should be taken into account."} {"id": "PMID:1264337", "title": "[Effect of parent attitudes on the development of psychomotor disorders in epileptic children].", "content": "The authors studied the problem of parental attitudes assuming that in epilepsy, besides the coexistent CNS damage, the intensity and frequency of convulsive seizures, and the mode and duration of treatment which influence the functions of the child, the attitude of the parents is also very important. In the studied material of 272 cases (146 boys and 126 girls) treated in the psychiatric department and out-patient clinic in the Institute of Paediatrics, Medical Academy in Warsaw for at least 3 years three main patterns of parental attitude towards the epileptic child have been recognized: 1. overprotective attitude (58%). 2. inconsistent attitude (32%). 3. rejecting attitude (8%). Depending on these attitudes certain disturbances of psychomotor development manifested themselves or intensified, mainly in the form abnormal development of emotions and cognitive functions as well as social adaptation. In the conclusions the authors stress the widespread occurrence of incorrect parental attitudes and the necessity of psychotherapeutic influence on the parents.", "contents": "[Effect of parent attitudes on the development of psychomotor disorders in epileptic children]. The authors studied the problem of parental attitudes assuming that in epilepsy, besides the coexistent CNS damage, the intensity and frequency of convulsive seizures, and the mode and duration of treatment which influence the functions of the child, the attitude of the parents is also very important. In the studied material of 272 cases (146 boys and 126 girls) treated in the psychiatric department and out-patient clinic in the Institute of Paediatrics, Medical Academy in Warsaw for at least 3 years three main patterns of parental attitude towards the epileptic child have been recognized: 1. overprotective attitude (58%). 2. inconsistent attitude (32%). 3. rejecting attitude (8%). Depending on these attitudes certain disturbances of psychomotor development manifested themselves or intensified, mainly in the form abnormal development of emotions and cognitive functions as well as social adaptation. In the conclusions the authors stress the widespread occurrence of incorrect parental attitudes and the necessity of psychotherapeutic influence on the parents."} {"id": "PMID:1264338", "title": "[Prevention of inappropriate bringing up of epileptic children by their families].", "content": "The author studied the cognitive and emotional aspect of parental attitudes towards the epileptic children using a modification of the Schaefer and Bell \"PARI\" questionnaire. Additional information was obtained during history taking from the mothers and from the analysis of case records. The studies were carried out on mothers of epileptic children and mothers of children without epielpsy and other chronic diseases. The obtained results indicate that there is a significant difference between the attitudes of mothers of epileptic children and those of healthy children in the aspect of \"excessive distance\" and \"excessive concentration\" in favour of the mothers of non-epileptic children. No significant difference was found in \"normal emotional contact\". In view of this pattern of parental attitudes directives are suggested for correction of errors made by mothers of epileptic children.", "contents": "[Prevention of inappropriate bringing up of epileptic children by their families]. The author studied the cognitive and emotional aspect of parental attitudes towards the epileptic children using a modification of the Schaefer and Bell \"PARI\" questionnaire. Additional information was obtained during history taking from the mothers and from the analysis of case records. The studies were carried out on mothers of epileptic children and mothers of children without epielpsy and other chronic diseases. The obtained results indicate that there is a significant difference between the attitudes of mothers of epileptic children and those of healthy children in the aspect of \"excessive distance\" and \"excessive concentration\" in favour of the mothers of non-epileptic children. No significant difference was found in \"normal emotional contact\". In view of this pattern of parental attitudes directives are suggested for correction of errors made by mothers of epileptic children."} {"id": "PMID:1264339", "title": "[Effect of diphenylhydantoin on a developed epileptogenic focus in cats with split cerebral hemispheres].", "content": "The purpose of this work was to assess the effects of DPH on a developed epileptogenic focus in cats with split cerebral hemispheres. The investigations were carried out on 12 cats with a chronic epileptogenic focus produced by means of aluminum method in the right motor area. In all cats the epileptogenic focus was found in EEG. All animals received DPH in daily doses of 8-15 mg/kg. In 2 cats they appeared before beginning of treatment. One of these cats died after 3 days from status epilepticus, the other survived status epilepticus and died after 42 days of DPH administration with signs of intoxication. In 3 cats clinical seizures developed during DPH treatment after 30.84 and 210 days. DPH was given during from 171 to 314 days. Clinical seizures appeared in these cats only sporadically and the animals were sacrificed after completion of investigations. In 7 out of 12 cats clinical seizures failed to develop despite presence of bioelectrically active epileptogenic seizures in the right motor area. Administration of DPH in cats with developed epileptogenic focus failed to prevent clinical seizures. In cats with seizures their control was limited by drug toxicity. In all animals toxic effects were observed although the serum DPH level was in the range 8-20 mug/ml.", "contents": "[Effect of diphenylhydantoin on a developed epileptogenic focus in cats with split cerebral hemispheres]. The purpose of this work was to assess the effects of DPH on a developed epileptogenic focus in cats with split cerebral hemispheres. The investigations were carried out on 12 cats with a chronic epileptogenic focus produced by means of aluminum method in the right motor area. In all cats the epileptogenic focus was found in EEG. All animals received DPH in daily doses of 8-15 mg/kg. In 2 cats they appeared before beginning of treatment. One of these cats died after 3 days from status epilepticus, the other survived status epilepticus and died after 42 days of DPH administration with signs of intoxication. In 3 cats clinical seizures developed during DPH treatment after 30.84 and 210 days. DPH was given during from 171 to 314 days. Clinical seizures appeared in these cats only sporadically and the animals were sacrificed after completion of investigations. In 7 out of 12 cats clinical seizures failed to develop despite presence of bioelectrically active epileptogenic seizures in the right motor area. Administration of DPH in cats with developed epileptogenic focus failed to prevent clinical seizures. In cats with seizures their control was limited by drug toxicity. In all animals toxic effects were observed although the serum DPH level was in the range 8-20 mug/ml."} {"id": "PMID:1264341", "title": "[Objective assessment of the effects of 5'5-diphenylhydantoin on cat motor activity].", "content": "The authors report the preliminary results of determinations of motor activity of cats receiving 5'5-diphenylhydantoin. The determinations were carried out by means of a special device recording all movements of the animals to ensure objective evaluation. Healthy cats were used for these experiments. They were giving DPH in doses up to 12 mg/kg daily, the maximal dose was reached gradually over a period of one month. It was found that in the observed time period several activity peaks occurred at night time from 6 p.m. to 6 a.m. These peaks were a stable phenomenon in a given cat but they varied from one animal to another. Thus the results could be compared in one cat only. During administration of DPH afall of general activity to 50% occurred, the \"great\" activity was reduced or even disappeared completely, and the periods of increased activity were changed.", "contents": "[Objective assessment of the effects of 5'5-diphenylhydantoin on cat motor activity]. The authors report the preliminary results of determinations of motor activity of cats receiving 5'5-diphenylhydantoin. The determinations were carried out by means of a special device recording all movements of the animals to ensure objective evaluation. Healthy cats were used for these experiments. They were giving DPH in doses up to 12 mg/kg daily, the maximal dose was reached gradually over a period of one month. It was found that in the observed time period several activity peaks occurred at night time from 6 p.m. to 6 a.m. These peaks were a stable phenomenon in a given cat but they varied from one animal to another. Thus the results could be compared in one cat only. During administration of DPH afall of general activity to 50% occurred, the \"great\" activity was reduced or even disappeared completely, and the periods of increased activity were changed."} {"id": "PMID:1264340", "title": "[Effect of epileptagenic focus on the process of learning and memory in cats].", "content": "Investigations were performed on 13 cats with epileptogenic focus developed after sectioning the optic chiasm and corpus callosum. Learning was begun 3 months after producing the epileptogenic focus by the aluminium method when it was bioelectrically active. Additionally in 6 cats DPH in daily doses of 10--15 mg/kg was given 3 months after development of the focus. Learning of these animals was begun 1--2 months after the beginning of DPH administration which was continued throughout the whole period of learning during a 3-month pause in learning, as well as at the time of memory testing. In all animals the time of conditioned reflex development and differentiation was delayed. Learning was more difficult in animals with epileptogenic focus receiving DPH than in the animals with the epileptogenic focus not receiving DPH. Learning was slightly worse in the hemisphere with the focus than in that without the focus. Presence of clinical epileptic seizures was without any significant effect on the time of learning with the exception of days on which clinical seizures occurred (the percent of responses was then lower). Disturbances of memory of acquired conditioned reflexes were found only in animals with clinical seizures.", "contents": "[Effect of epileptagenic focus on the process of learning and memory in cats]. Investigations were performed on 13 cats with epileptogenic focus developed after sectioning the optic chiasm and corpus callosum. Learning was begun 3 months after producing the epileptogenic focus by the aluminium method when it was bioelectrically active. Additionally in 6 cats DPH in daily doses of 10--15 mg/kg was given 3 months after development of the focus. Learning of these animals was begun 1--2 months after the beginning of DPH administration which was continued throughout the whole period of learning during a 3-month pause in learning, as well as at the time of memory testing. In all animals the time of conditioned reflex development and differentiation was delayed. Learning was more difficult in animals with epileptogenic focus receiving DPH than in the animals with the epileptogenic focus not receiving DPH. Learning was slightly worse in the hemisphere with the focus than in that without the focus. Presence of clinical epileptic seizures was without any significant effect on the time of learning with the exception of days on which clinical seizures occurred (the percent of responses was then lower). Disturbances of memory of acquired conditioned reflexes were found only in animals with clinical seizures."} {"id": "PMID:1264343", "title": "[Changes in cytohormonal cervical swabs in epileptic women].", "content": "In 16 women with epilepsy aged 18 to 38 years cytohormonal investigations were carried out during menstrual cycle. Swabs were obtained from the upper one-third of the vagina, fixed and stained by the method of Schorr. Oestrogen activity indices (PI, EI, MI) and progesterone activity indices (FI, CI) were calculated. With the exception of 2 cases in all patients the cycles were abnormal. In 1 cycle high values of oestrogen activity indices were found. In 13 patients (80%) monophasic, hypoestrogenic, cycles were observed without progesterone activity in the second phase of the cycle. The authors believe that very long anticonvulsant treatment as well as lower efficiency of the hypothalamo-hypophyseal system may reduce the level of steroid hormones produced by the ovaries which must, however, be confirmed by further clinical and experimental investigations.", "contents": "[Changes in cytohormonal cervical swabs in epileptic women]. In 16 women with epilepsy aged 18 to 38 years cytohormonal investigations were carried out during menstrual cycle. Swabs were obtained from the upper one-third of the vagina, fixed and stained by the method of Schorr. Oestrogen activity indices (PI, EI, MI) and progesterone activity indices (FI, CI) were calculated. With the exception of 2 cases in all patients the cycles were abnormal. In 1 cycle high values of oestrogen activity indices were found. In 13 patients (80%) monophasic, hypoestrogenic, cycles were observed without progesterone activity in the second phase of the cycle. The authors believe that very long anticonvulsant treatment as well as lower efficiency of the hypothalamo-hypophyseal system may reduce the level of steroid hormones produced by the ovaries which must, however, be confirmed by further clinical and experimental investigations."} {"id": "PMID:1264342", "title": "[Electrochemical blood properties in epileptic children].", "content": "The cell-plasma index of sodium and potassium ions was determined in 15 children with the diagnosis of epilepsy. Sodium and potassium were determined in the erythrocytes and plasma by means of flame photometer. Then the interphase electrical potential of these ions was calculated and compared with similar determinations in healthy children. In the epileptic children the index of Na ions was increased and that of K ions decreased. The index of cell-plasma distribution of these ions was increased also. Electrical interphase potential of these ions was 1.38 mV lower than in healthy children.", "contents": "[Electrochemical blood properties in epileptic children]. The cell-plasma index of sodium and potassium ions was determined in 15 children with the diagnosis of epilepsy. Sodium and potassium were determined in the erythrocytes and plasma by means of flame photometer. Then the interphase electrical potential of these ions was calculated and compared with similar determinations in healthy children. In the epileptic children the index of Na ions was increased and that of K ions decreased. The index of cell-plasma distribution of these ions was increased also. Electrical interphase potential of these ions was 1.38 mV lower than in healthy children."} {"id": "PMID:1264344", "title": "[Post-traumatic intracranial bleeding in epilepsy].", "content": "The authors describe 11 cases of intracranial haemorrhage developing during grand mal attacks. The attacks were frequent or very frequent, sometimes they were connected with withdrawal of anticonvulsant treatment or alcohol abuse. In the clinical pattern of changes disturbances of consciousness predominated together with signs of increasing intracranial pressure. In only one case subarachnoid haemorrhage was recognized, in the remaining cases multiple or single intracranial haematomas were found and treated successfully surgically. The possibility of traumatic origin of intracranial haemorrhages may be suggested by presence of cranial fractures. In the material of the authors intracranial bleedings were present in 40.2% of epileptic patients who suffered craniocerebral injury during a seizure.", "contents": "[Post-traumatic intracranial bleeding in epilepsy]. The authors describe 11 cases of intracranial haemorrhage developing during grand mal attacks. The attacks were frequent or very frequent, sometimes they were connected with withdrawal of anticonvulsant treatment or alcohol abuse. In the clinical pattern of changes disturbances of consciousness predominated together with signs of increasing intracranial pressure. In only one case subarachnoid haemorrhage was recognized, in the remaining cases multiple or single intracranial haematomas were found and treated successfully surgically. The possibility of traumatic origin of intracranial haemorrhages may be suggested by presence of cranial fractures. In the material of the authors intracranial bleedings were present in 40.2% of epileptic patients who suffered craniocerebral injury during a seizure."} {"id": "PMID:1264396", "title": "Predictive value of cervical dilatation rates. I. Primipara labor.", "content": "A modified version of Philpott's partogram was used to analyze primipara labor in Israel. The rate of cervical dilatation measure early in the active phase of labor (initial rate) is an accurate indicator of the outcome of labor. Ninety-three percent of primiparas with an initial cervical dilatation rate of 1.00 cm/hour or more delivered spontaneously. Seventy-six percent of those with an initial cervical dilatation rate of less than 1.00 cm/hour required an assisted delivery (forceps or vacuum) or cesarean section. The mean cervical dilatation rate for spontaneous deliveries as measured early in the active phase was 1.75 cm/hour. Patients needing an assisted delivery had a mean cervical dilatation rate of 0.93 cm/hour, and for cesarean section deliveries the mean rate was 0.42 cm/hour. No significant differences were observed among patients of different ethnic origins. The initial cervical dilatation rate proves to be useful in early identification of those patients who deliveries were complicated. The method avoids complicated cervicographs and is simple and reliable.", "contents": "Predictive value of cervical dilatation rates. I. Primipara labor. A modified version of Philpott's partogram was used to analyze primipara labor in Israel. The rate of cervical dilatation measure early in the active phase of labor (initial rate) is an accurate indicator of the outcome of labor. Ninety-three percent of primiparas with an initial cervical dilatation rate of 1.00 cm/hour or more delivered spontaneously. Seventy-six percent of those with an initial cervical dilatation rate of less than 1.00 cm/hour required an assisted delivery (forceps or vacuum) or cesarean section. The mean cervical dilatation rate for spontaneous deliveries as measured early in the active phase was 1.75 cm/hour. Patients needing an assisted delivery had a mean cervical dilatation rate of 0.93 cm/hour, and for cesarean section deliveries the mean rate was 0.42 cm/hour. No significant differences were observed among patients of different ethnic origins. The initial cervical dilatation rate proves to be useful in early identification of those patients who deliveries were complicated. The method avoids complicated cervicographs and is simple and reliable."} {"id": "PMID:1264397", "title": "The effect of unselected intrapartum fetal monitoring.", "content": "Experiences with unselected intrapartum fetal monitoring in the 3-year period from 1972-1974 are compared with those of the 3 preceding years before monitoring was instituted. The effect of monitoring all laboring patients is correlated with a significant decrease in the perinatal mortality and a significant increase in the cesarean section rate. There were 16 intrapartum deaths during the period before monitors were used compared to only 1 intrapartum death in the period when monitors were used. The advantages and disadvantages of unselected electronic monitoring are discussed. The importance of education of medical and paramedical personnel necessary for intense intrapartum care is emphasized.", "contents": "The effect of unselected intrapartum fetal monitoring. Experiences with unselected intrapartum fetal monitoring in the 3-year period from 1972-1974 are compared with those of the 3 preceding years before monitoring was instituted. The effect of monitoring all laboring patients is correlated with a significant decrease in the perinatal mortality and a significant increase in the cesarean section rate. There were 16 intrapartum deaths during the period before monitors were used compared to only 1 intrapartum death in the period when monitors were used. The advantages and disadvantages of unselected electronic monitoring are discussed. The importance of education of medical and paramedical personnel necessary for intense intrapartum care is emphasized."} {"id": "PMID:1264398", "title": "Postpartum and Postabortal Ovarian Vein Thrombophlebitis.", "content": "Six cases of ovarian vein thrombophlebitis are reported including one resulting in operative death, a case diagnosed by phlebography, a postabortal case, and a case followed by habitual abortion. An historic review of this disease is presented. It is suggested that the ovarian vein may be the most commonly involved vein in puerperal pelvic thrombophlebitis.", "contents": "Postpartum and Postabortal Ovarian Vein Thrombophlebitis. Six cases of ovarian vein thrombophlebitis are reported including one resulting in operative death, a case diagnosed by phlebography, a postabortal case, and a case followed by habitual abortion. An historic review of this disease is presented. It is suggested that the ovarian vein may be the most commonly involved vein in puerperal pelvic thrombophlebitis."} {"id": "PMID:1264399", "title": "Effects of terbutaline on human myometrial activity and endometrial blood flow.", "content": "The selective beta2-receptor stimulator, terbutaline (0.25-0.5 mg), was given intravenously to healthy women at different times in the menstrual cycle. Intrauterine pressure was recorded by means of a microtransducer catheter, and local endometrial blood flow followed by a thermistor technic based on measuring thermodilution. The general response to terbutaline was a decrease in uterine activity and an increase in blood flow. However, the effects varied with the menstrual phase, being maximum around the onset of menstruation and minimum at midcycle. Pretreatment with propranolol (1 mg IV) completely inhibited the effects of terbutaline.", "contents": "Effects of terbutaline on human myometrial activity and endometrial blood flow. The selective beta2-receptor stimulator, terbutaline (0.25-0.5 mg), was given intravenously to healthy women at different times in the menstrual cycle. Intrauterine pressure was recorded by means of a microtransducer catheter, and local endometrial blood flow followed by a thermistor technic based on measuring thermodilution. The general response to terbutaline was a decrease in uterine activity and an increase in blood flow. However, the effects varied with the menstrual phase, being maximum around the onset of menstruation and minimum at midcycle. Pretreatment with propranolol (1 mg IV) completely inhibited the effects of terbutaline."} {"id": "PMID:1264400", "title": "The Cervical Epithelium From Fetal Age to Adolescence.", "content": "Uteri obtained at the postmortem examination of 164 girls ranging in age from premature and immature infants to 11 years were studied for evidence regarding the developmental changes that take place in the cervix during this period of life and in particular the mechanisms involved in the production and regression of congenital ectropion. Tt is concluded that congenital ectropion is a normal feature of development of the cervix.Its occurrence and its persistence or disappearance appear to depend on variable growth of cervical tissues as they react to hormonal stimulation, hormonal deprivation, and systemic growth. The mechanisms are described in detail.", "contents": "The Cervical Epithelium From Fetal Age to Adolescence. Uteri obtained at the postmortem examination of 164 girls ranging in age from premature and immature infants to 11 years were studied for evidence regarding the developmental changes that take place in the cervix during this period of life and in particular the mechanisms involved in the production and regression of congenital ectropion. Tt is concluded that congenital ectropion is a normal feature of development of the cervix.Its occurrence and its persistence or disappearance appear to depend on variable growth of cervical tissues as they react to hormonal stimulation, hormonal deprivation, and systemic growth. The mechanisms are described in detail."} {"id": "PMID:1264401", "title": "Management of Postoperative Abscess Following Gynecologic Surgery.", "content": "Forty-nine postoperative abscesses were encountered following 1600 major pelvic procedures. Abdominal and vaginal procedures were complicated by abscess formation in 0.7% and 4% of cases, respectively. The average time between surgery and recognition of the pelvic abscess was 18 days. A positive correlation between surgery performed during the luteal phase and abscess formation was noted. Fifty-five percent of pelvic abscesses treated by primary vaginal drainage required eventful laparotomy for final eradiction of disease. An aggressive approach to abscess management is felt to be justified in this disease entity.", "contents": "Management of Postoperative Abscess Following Gynecologic Surgery. Forty-nine postoperative abscesses were encountered following 1600 major pelvic procedures. Abdominal and vaginal procedures were complicated by abscess formation in 0.7% and 4% of cases, respectively. The average time between surgery and recognition of the pelvic abscess was 18 days. A positive correlation between surgery performed during the luteal phase and abscess formation was noted. Fifty-five percent of pelvic abscesses treated by primary vaginal drainage required eventful laparotomy for final eradiction of disease. An aggressive approach to abscess management is felt to be justified in this disease entity."} {"id": "PMID:1264402", "title": "Effect of Crude and Purified hCG on Lymphocyte Blastogenesis.", "content": "Crude APL hCG completely inhibited blastogenesis induced by phytohemagglutinin, pokeweed mitogen, or concanavalin A in normal lymphocytes and lymphocytes obtained from cancer patients. Phenol in quantities comparable to its concentration in commercial lyophilized APL hCG also completely inhibited all three mitogenic responses. By contrast, similar doses of highly purified hCG had no inhibitory effect; higher concentrations produced only slight inhibition. Beta-hCG had a partial (less than 50%) inhibitory effect that was dose-independent and nonreproducible.", "contents": "Effect of Crude and Purified hCG on Lymphocyte Blastogenesis. Crude APL hCG completely inhibited blastogenesis induced by phytohemagglutinin, pokeweed mitogen, or concanavalin A in normal lymphocytes and lymphocytes obtained from cancer patients. Phenol in quantities comparable to its concentration in commercial lyophilized APL hCG also completely inhibited all three mitogenic responses. By contrast, similar doses of highly purified hCG had no inhibitory effect; higher concentrations produced only slight inhibition. Beta-hCG had a partial (less than 50%) inhibitory effect that was dose-independent and nonreproducible."} {"id": "PMID:1264403", "title": "Peripheral and Ovarian Steroids in Ovarian Hyperthecosis.", "content": "Serum levels of cortisol (F), pregnenolone (delta5-P), 17-hydroxypregnenolone (17-delta5-P), progesterone (P), 17-hydroxyprogesterone (17-P), androstenedione (A), testosterone (T), 5alphadihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), estrone (E1), and estradiol-17beta (E2) were measure in 2 virilized patients with ovarian hyperthecosis. Daily morning blood samples were obtained for 6 consecutive days. Dexamethasone (Dex) 2 mg/day was administered orally starting after venipuncture on the second day and continued for 5 days. Human chorionic gonadotropin (hCG) was administered intramuscularly on the afternoon of the fourth and fifth days. Following the suppression-stimulation test, both patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. At the time of surgery, samples of peripheral and ovarian vein blood were obtained for steroid measurements. Blood samples were also obtained postsurgery to evaluate the effect of ovariectomy on the steroid levels. Of significance were the following observations: 1)Although both patients were eumenorrheic, no corpus luteum or corpus albicans was seen on histologic examination of the ovaries. 2)Of the androgens measured, only peripheral T and DHT were elevated and did not suppress on Dex treatment, but decreased to low levels following ovariectomy, pointing toward the ovary as the source of excess T and DHT. Both patients had elevated T and DHT in the ovarian vein samples. 3)In 1 patient the ovarian vein samples shoed elevated F levels with a significant ovarian-peripheral venous gradient for this steroid, and indication of ovarian secretion of F in this patient. 4)The levels of 17-P were elevated in both patients, did not suppress on Dex, and increased markedly following hCG, suggesting the ovary as the source of excess 17-P. Since A levels were normal and did not increase concomitantly with 17-P levels following hCG, it is likely that the patients had a decreased activity of the ovarian C17-20 desmolase, the enzyme responsible for the conversion of 17-P to A.", "contents": "Peripheral and Ovarian Steroids in Ovarian Hyperthecosis. Serum levels of cortisol (F), pregnenolone (delta5-P), 17-hydroxypregnenolone (17-delta5-P), progesterone (P), 17-hydroxyprogesterone (17-P), androstenedione (A), testosterone (T), 5alphadihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), estrone (E1), and estradiol-17beta (E2) were measure in 2 virilized patients with ovarian hyperthecosis. Daily morning blood samples were obtained for 6 consecutive days. Dexamethasone (Dex) 2 mg/day was administered orally starting after venipuncture on the second day and continued for 5 days. Human chorionic gonadotropin (hCG) was administered intramuscularly on the afternoon of the fourth and fifth days. Following the suppression-stimulation test, both patients underwent abdominal hysterectomy and bilateral salpingo-oophorectomy. At the time of surgery, samples of peripheral and ovarian vein blood were obtained for steroid measurements. Blood samples were also obtained postsurgery to evaluate the effect of ovariectomy on the steroid levels. Of significance were the following observations: 1)Although both patients were eumenorrheic, no corpus luteum or corpus albicans was seen on histologic examination of the ovaries. 2)Of the androgens measured, only peripheral T and DHT were elevated and did not suppress on Dex treatment, but decreased to low levels following ovariectomy, pointing toward the ovary as the source of excess T and DHT. Both patients had elevated T and DHT in the ovarian vein samples. 3)In 1 patient the ovarian vein samples shoed elevated F levels with a significant ovarian-peripheral venous gradient for this steroid, and indication of ovarian secretion of F in this patient. 4)The levels of 17-P were elevated in both patients, did not suppress on Dex, and increased markedly following hCG, suggesting the ovary as the source of excess 17-P. Since A levels were normal and did not increase concomitantly with 17-P levels following hCG, it is likely that the patients had a decreased activity of the ovarian C17-20 desmolase, the enzyme responsible for the conversion of 17-P to A."} {"id": "PMID:1264404", "title": "Continuous Fetal Scalp and Carotid Artery Oxygen Tension Monitoring in the Sheep.", "content": "Fetal scalp and carotid PO2 were recorded continuously by polargraphic oxygen electrodes at several levels of maternal oxygenation. The results were compared to measurements obtained by intermittent blood samples using the radiometer blood gas analyzer. There was a good correlation between the PO2 values measured by the implanted oxygen electrodes and by conventional analyses of blood samples collected anaerobically. Electrode measurements differed from the control radiometer values by a mean of +/- 1.2 mmHg; 2 SD= +/- 2.50. Scalp PO2 recordings were lower but paralleled the carotid recordings under varying degrees of maternally inspired O2 concentrations. Thus scalp PO2 levels reflect closely those in the central fetal circulation. Administration of 95% O2 to the mother resulted in a 27% increase of scalp PO2 and a 29% increase in the carotid artery PO2 when compare to room air.", "contents": "Continuous Fetal Scalp and Carotid Artery Oxygen Tension Monitoring in the Sheep. Fetal scalp and carotid PO2 were recorded continuously by polargraphic oxygen electrodes at several levels of maternal oxygenation. The results were compared to measurements obtained by intermittent blood samples using the radiometer blood gas analyzer. There was a good correlation between the PO2 values measured by the implanted oxygen electrodes and by conventional analyses of blood samples collected anaerobically. Electrode measurements differed from the control radiometer values by a mean of +/- 1.2 mmHg; 2 SD= +/- 2.50. Scalp PO2 recordings were lower but paralleled the carotid recordings under varying degrees of maternally inspired O2 concentrations. Thus scalp PO2 levels reflect closely those in the central fetal circulation. Administration of 95% O2 to the mother resulted in a 27% increase of scalp PO2 and a 29% increase in the carotid artery PO2 when compare to room air."} {"id": "PMID:1264405", "title": "The Determination of Peroxidase in Amniotic Fluid.", "content": "Analyzing total peroxidase activity in amniotic fluid is extremely simple, requiring only 1 1/2 minutes of incubation at room temperature and a spectrophotometer. Peroxidase, clearly detectable at as early as 17 weeks' gestation in the amniotic fluid, increases 100-fold by term. The increase follows a predictable rising curve and can be used to estimate the fetal age. Maturation of the fetal salivary gland is most probably the source of rising amniotic fluid peroxidase levels. Samples from complicated pregnancies are lower than normal, do not increase as rapidly, and probably can be bracketed into their own ranges for gestational age evaluation.", "contents": "The Determination of Peroxidase in Amniotic Fluid. Analyzing total peroxidase activity in amniotic fluid is extremely simple, requiring only 1 1/2 minutes of incubation at room temperature and a spectrophotometer. Peroxidase, clearly detectable at as early as 17 weeks' gestation in the amniotic fluid, increases 100-fold by term. The increase follows a predictable rising curve and can be used to estimate the fetal age. Maturation of the fetal salivary gland is most probably the source of rising amniotic fluid peroxidase levels. Samples from complicated pregnancies are lower than normal, do not increase as rapidly, and probably can be bracketed into their own ranges for gestational age evaluation."} {"id": "PMID:1264406", "title": "The glucose-insulin ratio in amniotic fluid.", "content": "The purpose of this study is to present evidence that the glucose-insulin ratio in amniotic fluid is a prognostic indicator of the status of the fetus in utero and of the newborn in insulin-dependent diabetic pregnant women.", "contents": "The glucose-insulin ratio in amniotic fluid. The purpose of this study is to present evidence that the glucose-insulin ratio in amniotic fluid is a prognostic indicator of the status of the fetus in utero and of the newborn in insulin-dependent diabetic pregnant women."} {"id": "PMID:1264407", "title": "Management of intrauterine fetal demise and missed abortion using prostaglandin E2 vaginal suppositories.", "content": "Two hundred and twelve patients diagnosed as having a missed abortion or intrauterine fetal death were managed by the use of prostaglandin E2 vaginal suppositories. The method had a high efficacy rate with 98% of the patients experiencing successful evacuation of the uterine contents. The mean time to abortion was 10.9 hours with a mean dose of 60 mg (3 suppositories). Side effects were well tolerated. Transient pyrexia was present in 36% of the patients during therapy, but returned to pretreatment levels after abortion. No intrauterine infection was observed. The risks associated with active treatment can be avoided. The ease of administration permits initiation of therapy as soon as the diagnosis is confirmed.", "contents": "Management of intrauterine fetal demise and missed abortion using prostaglandin E2 vaginal suppositories. Two hundred and twelve patients diagnosed as having a missed abortion or intrauterine fetal death were managed by the use of prostaglandin E2 vaginal suppositories. The method had a high efficacy rate with 98% of the patients experiencing successful evacuation of the uterine contents. The mean time to abortion was 10.9 hours with a mean dose of 60 mg (3 suppositories). Side effects were well tolerated. Transient pyrexia was present in 36% of the patients during therapy, but returned to pretreatment levels after abortion. No intrauterine infection was observed. The risks associated with active treatment can be avoided. The ease of administration permits initiation of therapy as soon as the diagnosis is confirmed."} {"id": "PMID:1264408", "title": "Electroencephalographic changes following intraamniotic prostaglandin F2 alpha administration for therapeutic abortion.", "content": "Electroencephalograms were obtained on 43 patients undergoing therapeutic second trimester abortion using intraamniotic prostaglandin F2alpha. Recordings were made before and 4 hours after prostaglandin administration, as well as 4 hours after the abortion. At 4 hours after prostaglandin administration, 30% of the women had abnormal tracings, while 50% of the women had abnormal recordings 4 hours postabortion. Although the changes consisted primarily of mild generalized or lateralized slowing, 4 patients developed paroxysmal activity not initially present. This finding would seem to suggest a potential relationship between PGF2alpha administration and clinical seizures.", "contents": "Electroencephalographic changes following intraamniotic prostaglandin F2 alpha administration for therapeutic abortion. Electroencephalograms were obtained on 43 patients undergoing therapeutic second trimester abortion using intraamniotic prostaglandin F2alpha. Recordings were made before and 4 hours after prostaglandin administration, as well as 4 hours after the abortion. At 4 hours after prostaglandin administration, 30% of the women had abnormal tracings, while 50% of the women had abnormal recordings 4 hours postabortion. Although the changes consisted primarily of mild generalized or lateralized slowing, 4 patients developed paroxysmal activity not initially present. This finding would seem to suggest a potential relationship between PGF2alpha administration and clinical seizures."} {"id": "PMID:1264409", "title": "Locked twins. An unusual method of delivery.", "content": "This report concerns a case of locked twins encountered at the Mayo Clinic. The method of delivery is unusual, and the fact that both infants survived is also worthy of reporting.", "contents": "Locked twins. An unusual method of delivery. This report concerns a case of locked twins encountered at the Mayo Clinic. The method of delivery is unusual, and the fact that both infants survived is also worthy of reporting."} {"id": "PMID:1264410", "title": "A method of Pomeroy tubal ligation reanastomosis.", "content": "A method of reanastomosis of the uterine tube after Pomeroy tubal ligation is presented. The pregnancy rate was 69%. The viable birth rate was 38%, with 1 ectopic pregnancy, 2 patients pregnant, and 1 patient lost to followup at the time of this report.", "contents": "A method of Pomeroy tubal ligation reanastomosis. A method of reanastomosis of the uterine tube after Pomeroy tubal ligation is presented. The pregnancy rate was 69%. The viable birth rate was 38%, with 1 ectopic pregnancy, 2 patients pregnant, and 1 patient lost to followup at the time of this report."} {"id": "PMID:1264415", "title": "A new method to achieve complete akinesia of the facial muscles of the eyelids.", "content": "Blocking the facial nerve by injecting anesthetic agent over the most posterior, most superior palpable aspect of the ramus of the mandible produces more reliably complete facial nerve akinesia than obtained by the standard techniques used to obtain facial akinesia. The position is posterior and inferior to the point chosen for the classical O'Brien block. This new technique is safe and no complications have been noted in over 10 years of use. It is highly recommended as a method of achieving total hemifacial akinesia for ophthalmic procedures.", "contents": "A new method to achieve complete akinesia of the facial muscles of the eyelids. Blocking the facial nerve by injecting anesthetic agent over the most posterior, most superior palpable aspect of the ramus of the mandible produces more reliably complete facial nerve akinesia than obtained by the standard techniques used to obtain facial akinesia. The position is posterior and inferior to the point chosen for the classical O'Brien block. This new technique is safe and no complications have been noted in over 10 years of use. It is highly recommended as a method of achieving total hemifacial akinesia for ophthalmic procedures."} {"id": "PMID:1264416", "title": "Iridectomy in rubeosis iridis.", "content": "Creating an iridectomy in the face of rubeosis iridis carries a significant risk of hyphema. A technique is described utilizing a bipolar micro-cautery to cauterize iris vessels under direct observation before cutting iris tissue. This allows the iridectomy to be performed with less risk of intraocular bleeding.", "contents": "Iridectomy in rubeosis iridis. Creating an iridectomy in the face of rubeosis iridis carries a significant risk of hyphema. A technique is described utilizing a bipolar micro-cautery to cauterize iris vessels under direct observation before cutting iris tissue. This allows the iridectomy to be performed with less risk of intraocular bleeding."} {"id": "PMID:1264418", "title": "Surgical repair of a traumatized shrunken eye.", "content": "A 50-year-old Japanese man underwent removal of a traumatic cataract with an intralenticular foreign body. Surgery was complicated by an unplanned extracapsular delivery of the lens and vitreous loss. Two years later, with a visual acuity of hand motions and signs of phthisis bulbi, he had a vitrectomy that cleared the media to reveal a rhegmatogenous retinal detachment. The detachment was treated by cryopexy, scleral buckling, and intraocular gas injection. One year after this combined procedure, his best corrected visual acuity was 20/400 with clear media and attached retina.", "contents": "Surgical repair of a traumatized shrunken eye. A 50-year-old Japanese man underwent removal of a traumatic cataract with an intralenticular foreign body. Surgery was complicated by an unplanned extracapsular delivery of the lens and vitreous loss. Two years later, with a visual acuity of hand motions and signs of phthisis bulbi, he had a vitrectomy that cleared the media to reveal a rhegmatogenous retinal detachment. The detachment was treated by cryopexy, scleral buckling, and intraocular gas injection. One year after this combined procedure, his best corrected visual acuity was 20/400 with clear media and attached retina."} {"id": "PMID:1264419", "title": "The partial-punch: a new combined cataract-glaucoma operation.", "content": "This report describes a new combined cataract extraction-glaucoma procedure. The technique is a modification of a standard filtration type of operation. The essential step is the development of a shelved posterior scleral lip, 4 mm of which is excised; full thickness sclera is not removed. This permits tight incisional closure, but with the presence of a \"valve\" permitting exit of aqueous under a prepared conjunctival flap should intraocular pressure rise significantly in the postoperative period. In 15 cases there were no serious complications, no flat anterior chamber, good pressure control in 14 cases, and filtering blebs in nine.", "contents": "The partial-punch: a new combined cataract-glaucoma operation. This report describes a new combined cataract extraction-glaucoma procedure. The technique is a modification of a standard filtration type of operation. The essential step is the development of a shelved posterior scleral lip, 4 mm of which is excised; full thickness sclera is not removed. This permits tight incisional closure, but with the presence of a \"valve\" permitting exit of aqueous under a prepared conjunctival flap should intraocular pressure rise significantly in the postoperative period. In 15 cases there were no serious complications, no flat anterior chamber, good pressure control in 14 cases, and filtering blebs in nine."} {"id": "PMID:1264420", "title": "Cataract extraction in pathological myopia.", "content": "Fifty-three cataract extractions in eyes with pathological myopia effected visual improvement in 47 eyes (89%). The median visual acuity increased from a preoperative level of 20/300 to 20/40 postoperatively. The incidence in this series of vitreous loss (1.9%) and retinal detachment (1.9%), are within the expected range of such complications. Four cases developed aphakic glaucoma which has necessitated continued therapy. All four had both enzyme zonulolysis and topical steroids, postoperatively. Other problems unique to surgery in these eyes are the missed diagnosis of nuclear cataract, possible dislocation of the lens, perforation of the sclera during retrobulbar injection, and rupture of the globe with vigorous digital massage.", "contents": "Cataract extraction in pathological myopia. Fifty-three cataract extractions in eyes with pathological myopia effected visual improvement in 47 eyes (89%). The median visual acuity increased from a preoperative level of 20/300 to 20/40 postoperatively. The incidence in this series of vitreous loss (1.9%) and retinal detachment (1.9%), are within the expected range of such complications. Four cases developed aphakic glaucoma which has necessitated continued therapy. All four had both enzyme zonulolysis and topical steroids, postoperatively. Other problems unique to surgery in these eyes are the missed diagnosis of nuclear cataract, possible dislocation of the lens, perforation of the sclera during retrobulbar injection, and rupture of the globe with vigorous digital massage."} {"id": "PMID:1264421", "title": "Clinical and ultrastructural correlation in congenital and acquired ptosis.", "content": "The levator superioris muscle has been studied with the light microscope and the electron microscope in congenital and acquired ptosis. Ultrastructural finding correlated closely with the clinical entities. Congenital ptosis appears to be on a myogenic basis. Acquired ptosis ultrastructurally indicates a regenerative process.", "contents": "Clinical and ultrastructural correlation in congenital and acquired ptosis. The levator superioris muscle has been studied with the light microscope and the electron microscope in congenital and acquired ptosis. Ultrastructural finding correlated closely with the clinical entities. Congenital ptosis appears to be on a myogenic basis. Acquired ptosis ultrastructurally indicates a regenerative process."} {"id": "PMID:1264422", "title": "Epiphora following rhinoplasty and Caldwell-Luc procedures.", "content": "Cosmetic rhinoplasty and maxillary sinus surgery are rare causes of lacrimal obstruction. The lacrimal sac is quite vulnerable to damage by the lateral osteotomy of the rhinoplasty. While obstruction from such damage usually resolves in three months, these three cases illustrate the risk of perisitent obstruction, particularly in complicated cases. The nasoantral window in the Caldwell-Luc may damage the distal lacrimal opening if it is placed too high, or made too large. Occasionally, the duct will extend more anterior and inferior and be quite vulnerable to damage by the nasal antrostomy.", "contents": "Epiphora following rhinoplasty and Caldwell-Luc procedures. Cosmetic rhinoplasty and maxillary sinus surgery are rare causes of lacrimal obstruction. The lacrimal sac is quite vulnerable to damage by the lateral osteotomy of the rhinoplasty. While obstruction from such damage usually resolves in three months, these three cases illustrate the risk of perisitent obstruction, particularly in complicated cases. The nasoantral window in the Caldwell-Luc may damage the distal lacrimal opening if it is placed too high, or made too large. Occasionally, the duct will extend more anterior and inferior and be quite vulnerable to damage by the nasal antrostomy."} {"id": "PMID:1264423", "title": "Intraocular microsurgery: I. New instrumentation (SITE).", "content": "The SITE instrument appears to combine advantages of other instruments previously described. It meets the proposed objectives of an efficient cutter where tissue is removed at the front end of the tip. It allows the surgeon complete control of the suction and reflux systems. The instrument is of a simple modular dsign. A fiber optic attachment is available. It is dependable and safe.", "contents": "Intraocular microsurgery: I. New instrumentation (SITE). The SITE instrument appears to combine advantages of other instruments previously described. It meets the proposed objectives of an efficient cutter where tissue is removed at the front end of the tip. It allows the surgeon complete control of the suction and reflux systems. The instrument is of a simple modular dsign. A fiber optic attachment is available. It is dependable and safe."} {"id": "PMID:1264426", "title": "Teratogenesis.", "content": "In this presentation the scope of the problem of teratogenesis and the essentials of teratology are briefly reviewed. The teratogenicity of any compound is a reflection of a complex interaction of the compound with both the maternal and fetal tissues, the genetic background of the fetus, and the time sequence of gestational events. Under such circumstances the implication of a single compound as a teratogen is difficult, a fact reflected in the high percentage of congenital morphologic abnormalities for which no cause can be ascribed. Four compounds--thalidomide, anticonvulsants, alcohol, and folic acid antagonists--with a known teratogenetic effect on the musculoskeletal system are discussed, as is the role of the orthopedic surgeon in teratology.", "contents": "Teratogenesis. In this presentation the scope of the problem of teratogenesis and the essentials of teratology are briefly reviewed. The teratogenicity of any compound is a reflection of a complex interaction of the compound with both the maternal and fetal tissues, the genetic background of the fetus, and the time sequence of gestational events. Under such circumstances the implication of a single compound as a teratogen is difficult, a fact reflected in the high percentage of congenital morphologic abnormalities for which no cause can be ascribed. Four compounds--thalidomide, anticonvulsants, alcohol, and folic acid antagonists--with a known teratogenetic effect on the musculoskeletal system are discussed, as is the role of the orthopedic surgeon in teratology."} {"id": "PMID:1264428", "title": "Dislocation of the hip in birth defects.", "content": "Several heritable disorders--although rare--are reviewed that are directly or indirectly related to dislocation of the hip. With the ever increasing list of clinical syndromes and our growing understanding of genetics, the physician who first sees these patients should broaden his views to identify these conditions and establish the diagnosis. The effectiveness of treatment often depends upon such knowledge.", "contents": "Dislocation of the hip in birth defects. Several heritable disorders--although rare--are reviewed that are directly or indirectly related to dislocation of the hip. With the ever increasing list of clinical syndromes and our growing understanding of genetics, the physician who first sees these patients should broaden his views to identify these conditions and establish the diagnosis. The effectiveness of treatment often depends upon such knowledge."} {"id": "PMID:1264429", "title": "Congenital deformities about the knee.", "content": "Congenital deformities about the knee are the result of abnormalities of all the anatomical structures that make up this joint. In some cases the structural changes observed are due to primary disorders of formation and growth of one or more of the anatomical components of the knee. Disorders are known to occur in the integumentary, muscular, ligamentous supporting, and skeletal systems. Examples of these disorders are seen in the bone dysplasias and joint laxity syndromes. In other cases exaggerated intrauterine positions of the limb seem to bring about certain adaptive changes in the embryological development of this joint. Epiphyseal dysplasias can lead to precocious arthropathy. Subluxation of the patella is often an indicator of a ligamentous laxity syndrome. It can also occur as a result of anatomical abnormalities of the femoral condyles or be due to congenital or acquired quadriceps fibrosis. Hypoplasia of the patella with dislocation is seen in the nail-patella syndrome.", "contents": "Congenital deformities about the knee. Congenital deformities about the knee are the result of abnormalities of all the anatomical structures that make up this joint. In some cases the structural changes observed are due to primary disorders of formation and growth of one or more of the anatomical components of the knee. Disorders are known to occur in the integumentary, muscular, ligamentous supporting, and skeletal systems. Examples of these disorders are seen in the bone dysplasias and joint laxity syndromes. In other cases exaggerated intrauterine positions of the limb seem to bring about certain adaptive changes in the embryological development of this joint. Epiphyseal dysplasias can lead to precocious arthropathy. Subluxation of the patella is often an indicator of a ligamentous laxity syndrome. It can also occur as a result of anatomical abnormalities of the femoral condyles or be due to congenital or acquired quadriceps fibrosis. Hypoplasia of the patella with dislocation is seen in the nail-patella syndrome."} {"id": "PMID:1264430", "title": "Foot deformities.", "content": "A list of syndromes that include foot deformities as part of the clinical presentation has been compiled and subdivided into a descriptive classification. A brief discussion is presented of the embryology of the foot as it pertains to and helps explain the etiology of these various anomalies. Variations in the treatment of arthrogryposis multiplex congenita and ring constrictions are described. Finally, unique foot configurations are documented, which if seen should alert the clinician to consider the diagnosis of a specific syndrome.", "contents": "Foot deformities. A list of syndromes that include foot deformities as part of the clinical presentation has been compiled and subdivided into a descriptive classification. A brief discussion is presented of the embryology of the foot as it pertains to and helps explain the etiology of these various anomalies. Variations in the treatment of arthrogryposis multiplex congenita and ring constrictions are described. Finally, unique foot configurations are documented, which if seen should alert the clinician to consider the diagnosis of a specific syndrome."} {"id": "PMID:1264431", "title": "The radial clubhand.", "content": "Deficiency of the radial ray is both isolated and syndromatic. Before treatment is undertaken, careful consideration has to be given to the entire child. In individuals in whom treatment is indicated, a program of plasters, centralization, and prolonged intramedullary rod fixation is recommended.", "contents": "The radial clubhand. Deficiency of the radial ray is both isolated and syndromatic. Before treatment is undertaken, careful consideration has to be given to the entire child. In individuals in whom treatment is indicated, a program of plasters, centralization, and prolonged intramedullary rod fixation is recommended."} {"id": "PMID:1264433", "title": "Orthopedic aspects of bone dysplasias.", "content": "Although the number of bone dysplasias and their variable forms of expression seem to be increasing almost daily, in almost all instances orthopedic disease is detected at rather specific locations--the cervical spine, the thoracic and lumbar spine, and the knee and hips--and the orthopedic deformity is surprisingly constant.", "contents": "Orthopedic aspects of bone dysplasias. Although the number of bone dysplasias and their variable forms of expression seem to be increasing almost daily, in almost all instances orthopedic disease is detected at rather specific locations--the cervical spine, the thoracic and lumbar spine, and the knee and hips--and the orthopedic deformity is surprisingly constant."} {"id": "PMID:1264434", "title": "Limb deficiencies and prosthetic devices.", "content": "The child with a congenital limb deficiency is best managed by an interdisciplinary clinic team, which can see him early and work with parents and agencies to provide adequate and early prosthetic prescriptions. Terminal transverse limb deficiencies are generally fitted similarly to the patient with acquired amputation at the same level. Other deficiencies often require nonstandard prosthetic devices in association with corrective or conversion surgery.", "contents": "Limb deficiencies and prosthetic devices. The child with a congenital limb deficiency is best managed by an interdisciplinary clinic team, which can see him early and work with parents and agencies to provide adequate and early prosthetic prescriptions. Terminal transverse limb deficiencies are generally fitted similarly to the patient with acquired amputation at the same level. Other deficiencies often require nonstandard prosthetic devices in association with corrective or conversion surgery."} {"id": "PMID:1264439", "title": "The role of the psychiatrist in myelodysplasia.", "content": "Management of the myelodysplasia patient and his family is best performed in the multidisciplinary setting of a comprehensive care clinic. Careful initial evaluation by each subspecialist on the team followed by family counseling provides the basis for selection of patients for treatment. Subsequently each subspecialist contributes up-to-date assessment and on-going medical care. Prevention of progressive orthopedic deformity through the use of plaster casts may minimize the need for surgical treatment. Severe deformities may require muscle balancing procedures. Aggressive surgical intervention is indicated in cases of progressive scoliosis and lordoscoliosis. Minimal urologic evaluation and surveillance guidelines have been developed, and prevention of irreversible renal damage is possible. Chemotherapy, adequate bladder drainage, and sophisticated techniques including sphincter and bladder electromyography and the use of artificial urinary sphincters and bladder pacemakers contribute to improved urologic management. The emotional needs of the patient and his family are complex, and support by the psychiatrist and the social worker as well as all other team members is necessary for adequate development of a well adjusted child in the face of physical handicaps.", "contents": "The role of the psychiatrist in myelodysplasia. Management of the myelodysplasia patient and his family is best performed in the multidisciplinary setting of a comprehensive care clinic. Careful initial evaluation by each subspecialist on the team followed by family counseling provides the basis for selection of patients for treatment. Subsequently each subspecialist contributes up-to-date assessment and on-going medical care. Prevention of progressive orthopedic deformity through the use of plaster casts may minimize the need for surgical treatment. Severe deformities may require muscle balancing procedures. Aggressive surgical intervention is indicated in cases of progressive scoliosis and lordoscoliosis. Minimal urologic evaluation and surveillance guidelines have been developed, and prevention of irreversible renal damage is possible. Chemotherapy, adequate bladder drainage, and sophisticated techniques including sphincter and bladder electromyography and the use of artificial urinary sphincters and bladder pacemakers contribute to improved urologic management. The emotional needs of the patient and his family are complex, and support by the psychiatrist and the social worker as well as all other team members is necessary for adequate development of a well adjusted child in the face of physical handicaps."} {"id": "PMID:1264440", "title": "Arthrogryposis of the upper extremity.", "content": "Patients with arthrogryposis multiplex congenita of the upper extremities can be helped a great deal by comparatively minor procedures. At the outset it is important to decide which patients can be helped and which patients cannot owing to the severity of disease or the social situation. It is also important, of course, to decide which patients do not require surgical or other methods of treatment. Once these decisions are made, one can safely begin in most patients with nonoperative measures, which consist of serial corrective cast applications starting at birth with changes every two to five days initially and then less often as the deformity is corrected. In patients who do not respond to this treatment, surgical intervention is necessary. We feel that surgery will be necessary in a great many of these patients. Surgery most often consists of soft tissue releases about the elbow, principally posterior capsulotomy, and triceps lengthening with or without tendon transfers to gain active motion. In the shoulder, surgery is rarely indicated, and when it is, this will be an osteotomy. In the wrist and hand, bone operations are almost always indicated because soft tissue procedures usually fail. These patients have two advantages in spite of their severe problems: They have normal sensation and they are usually of average or above average intelligence. Any improvement in the position of their extremities and any decrease in deformity will improve their functioning significantly.", "contents": "Arthrogryposis of the upper extremity. Patients with arthrogryposis multiplex congenita of the upper extremities can be helped a great deal by comparatively minor procedures. At the outset it is important to decide which patients can be helped and which patients cannot owing to the severity of disease or the social situation. It is also important, of course, to decide which patients do not require surgical or other methods of treatment. Once these decisions are made, one can safely begin in most patients with nonoperative measures, which consist of serial corrective cast applications starting at birth with changes every two to five days initially and then less often as the deformity is corrected. In patients who do not respond to this treatment, surgical intervention is necessary. We feel that surgery will be necessary in a great many of these patients. Surgery most often consists of soft tissue releases about the elbow, principally posterior capsulotomy, and triceps lengthening with or without tendon transfers to gain active motion. In the shoulder, surgery is rarely indicated, and when it is, this will be an osteotomy. In the wrist and hand, bone operations are almost always indicated because soft tissue procedures usually fail. These patients have two advantages in spite of their severe problems: They have normal sensation and they are usually of average or above average intelligence. Any improvement in the position of their extremities and any decrease in deformity will improve their functioning significantly."} {"id": "PMID:1264441", "title": "Arthrogryposis multiplex congenita of the lower extremity: report of two siblings.", "content": "The purpose of treatment of arthrogryposis of the lower extremities is to achieve a stable functional weight bearing position of the affected joints. One cannot expect to achieve normal mobility and gait unless the process is mild. Achieving a functional weight bearing position of a joint may be extremely difficult, requiring repeated surgical procedures. Maintenance of correction, although often imperfect, is vital during the growing period.", "contents": "Arthrogryposis multiplex congenita of the lower extremity: report of two siblings. The purpose of treatment of arthrogryposis of the lower extremities is to achieve a stable functional weight bearing position of the affected joints. One cannot expect to achieve normal mobility and gait unless the process is mild. Achieving a functional weight bearing position of a joint may be extremely difficult, requiring repeated surgical procedures. Maintenance of correction, although often imperfect, is vital during the growing period."} {"id": "PMID:1264463", "title": "The effects of prolonged consumption of wholemeal bread upon metabolism of calcium, magnesium, zinc and phosphorus of two young American adults.", "content": "The ability to adapt to a large daily intake of unleavened bread made from wheaten wholemeals of high extraction rate was examined in two young Americans who had not previously consumed fiber, phytate-, and phosphate-rich bread of this type. Adaptation was evaluated by comparing balances of zinc, calcium, magnesium, and phosphorus for a 12 day period after ten days of bread consumption with those during a similar period after 50 days and also by observing changes in blood composition during this period of bread consumption. Significantly negative balances of zinc, magnesium and phosphorus were observed in the initial period. However, all had become positive or nearly so after 50 days. By contrast, calcium balances which were also negative during the initial period remained negative at the end of the study. Plasma calcium and zinc concentrations had declined to low normal or subnormal values at this time. The failure to overcome the disturbing effects of consumption of wholemeal bread upon calcium metabolism occurred despite daily exposure to sunshine for many hours under conditions favorable for Vitamin D biosynthesis.", "contents": "The effects of prolonged consumption of wholemeal bread upon metabolism of calcium, magnesium, zinc and phosphorus of two young American adults. The ability to adapt to a large daily intake of unleavened bread made from wheaten wholemeals of high extraction rate was examined in two young Americans who had not previously consumed fiber, phytate-, and phosphate-rich bread of this type. Adaptation was evaluated by comparing balances of zinc, calcium, magnesium, and phosphorus for a 12 day period after ten days of bread consumption with those during a similar period after 50 days and also by observing changes in blood composition during this period of bread consumption. Significantly negative balances of zinc, magnesium and phosphorus were observed in the initial period. However, all had become positive or nearly so after 50 days. By contrast, calcium balances which were also negative during the initial period remained negative at the end of the study. Plasma calcium and zinc concentrations had declined to low normal or subnormal values at this time. The failure to overcome the disturbing effects of consumption of wholemeal bread upon calcium metabolism occurred despite daily exposure to sunshine for many hours under conditions favorable for Vitamin D biosynthesis."} {"id": "PMID:1264464", "title": "Advisability of surgical treatment for chronic membranous obstruction of the hepatic portion of the inferior vena cava.", "content": "Transatrial membranotomy was performed in a patient with membranous obstruction of the hepatic segment of the inferior vena cava, manifesting as longstanding varicosity and edema of the legs, chronic type of Budd-Chiari syndrome, liver cirrhosis and hypersplenism. The course in this patient and similar ones reported in the literature suggests a conservative approach.", "contents": "Advisability of surgical treatment for chronic membranous obstruction of the hepatic portion of the inferior vena cava. Transatrial membranotomy was performed in a patient with membranous obstruction of the hepatic segment of the inferior vena cava, manifesting as longstanding varicosity and edema of the legs, chronic type of Budd-Chiari syndrome, liver cirrhosis and hypersplenism. The course in this patient and similar ones reported in the literature suggests a conservative approach."} {"id": "PMID:1264465", "title": "Peptic ulcer in Iranian children.", "content": "Thirty cases of peptic ulcer were presented, all of which were diagnosed in accordance with strict radiological criteria. Upper abdominal pain was the most common presenting symptom. Hemorrhage occurred in 36.6% of the cases, and 16.6% suffered from melena and hematemesis requiring transfusions on admission. The only fatal case was due to perforation of a duodenal ulcer. Almost all of the children came from lower income groups and were inhabitants of Tehran or the suburbs. The incidence of peptic ulcer in Iranian children is 15.1 per ten thousand with 60% of the cases occurring in females. This suggests that peptic ulcer may be more common in Iran when compared to Europe or the United States and taht more cases occur in female children in Iran.", "contents": "Peptic ulcer in Iranian children. Thirty cases of peptic ulcer were presented, all of which were diagnosed in accordance with strict radiological criteria. Upper abdominal pain was the most common presenting symptom. Hemorrhage occurred in 36.6% of the cases, and 16.6% suffered from melena and hematemesis requiring transfusions on admission. The only fatal case was due to perforation of a duodenal ulcer. Almost all of the children came from lower income groups and were inhabitants of Tehran or the suburbs. The incidence of peptic ulcer in Iranian children is 15.1 per ten thousand with 60% of the cases occurring in females. This suggests that peptic ulcer may be more common in Iran when compared to Europe or the United States and taht more cases occur in female children in Iran."} {"id": "PMID:1264467", "title": "Effect of electrolytic lesions of the medullary inspiratory region in rats.", "content": "The medulla oblongatas of 48 anesthetized rats were explored by electrical stimulation. The pneumotachogram and in some, the arterial blood pressure as well, were recorded. The inspiratory area was located in the ventral reticular formation from the obex to 1.8 mm rostral to the obex. It occupied about 2.2 mm3 on each side of the midline. The expiratory reactive points were scattered in a region which was dorsal and caudal to the inspiratory area. Unilateral and midline lesions produced by 3, 5 and 8 ma direct current did not stop rhythmic respiration. There was an initial increase in the respiratory rate followed by diminution to below that of the prelesion time. The respiratory air flow was decreased. The changes in respiratory rate and air flow were not statistically significant in majority of the above groups. Bilateral lesions produced by 3 or 5 ma stopped breathing. Continuation of thythmic respiration after destruction of a number of inspiratory neurons and/or fibers in the midline or one side of the medulla indicates that all the inspiratory neurons and fibers are not essential for the maintenance of respiration. Cessation of thythmic respiration after destruction of all or most of inspiratory neurons on both sides of the midline indicates the essential role of the medulla-oblongata for genesis or maintenance of rhythmic respiration.", "contents": "Effect of electrolytic lesions of the medullary inspiratory region in rats. The medulla oblongatas of 48 anesthetized rats were explored by electrical stimulation. The pneumotachogram and in some, the arterial blood pressure as well, were recorded. The inspiratory area was located in the ventral reticular formation from the obex to 1.8 mm rostral to the obex. It occupied about 2.2 mm3 on each side of the midline. The expiratory reactive points were scattered in a region which was dorsal and caudal to the inspiratory area. Unilateral and midline lesions produced by 3, 5 and 8 ma direct current did not stop rhythmic respiration. There was an initial increase in the respiratory rate followed by diminution to below that of the prelesion time. The respiratory air flow was decreased. The changes in respiratory rate and air flow were not statistically significant in majority of the above groups. Bilateral lesions produced by 3 or 5 ma stopped breathing. Continuation of thythmic respiration after destruction of a number of inspiratory neurons and/or fibers in the midline or one side of the medulla indicates that all the inspiratory neurons and fibers are not essential for the maintenance of respiration. Cessation of thythmic respiration after destruction of all or most of inspiratory neurons on both sides of the midline indicates the essential role of the medulla-oblongata for genesis or maintenance of rhythmic respiration."} {"id": "PMID:1264468", "title": "Beta-adrenergic receptors and the effect of beta-adrenergic blocking agent propranolol on histamine and reserpine stimulated gastric acid secretion in man: normals and duodenal ulcer cases.", "content": "The effects of the beta adrenergic stimulant drug, \"Nylidrin\", and the beta adrenergic blocking agent, \"Propranolol\", on human basal gastric acid secretion were studied in 20 healthy volunteer subjects and 10 chronic D.U. cases. Nylidrin increased gastric acid secretion and volume. All effects of nylidrin were blocked by prior administration of beta adrenergic inhibitor propranolol. Propranolol diminished both acid secretion and volume in both normal and D.U. cases. The presence of beta adrenergic receptors in the human stomach was suggested. The effects of beta adrenergic blocking agent propranolol on gastric secretion, stimulated with histamine, were studied in 10 normal subjects and 10 cases of chronic duodenal ulcer patients. Pretreatment with propranolol produced a signigicant depression of the 90 minute acid response to histamine in both volume and acidity in normals and duodenal ulcer cases. It is concluded that propranolol has an antisecretory effect, not only on basal gastric secretion but also on histamine stimulated secretion in man. Reserpine stimulated gastric acid secretion and volume in normals but showed no similar effect in D.U. cases. After pretreatment with propranolol it reduces the gastric acid secretion and volume in normals and D.U. cases.", "contents": "Beta-adrenergic receptors and the effect of beta-adrenergic blocking agent propranolol on histamine and reserpine stimulated gastric acid secretion in man: normals and duodenal ulcer cases. The effects of the beta adrenergic stimulant drug, \"Nylidrin\", and the beta adrenergic blocking agent, \"Propranolol\", on human basal gastric acid secretion were studied in 20 healthy volunteer subjects and 10 chronic D.U. cases. Nylidrin increased gastric acid secretion and volume. All effects of nylidrin were blocked by prior administration of beta adrenergic inhibitor propranolol. Propranolol diminished both acid secretion and volume in both normal and D.U. cases. The presence of beta adrenergic receptors in the human stomach was suggested. The effects of beta adrenergic blocking agent propranolol on gastric secretion, stimulated with histamine, were studied in 10 normal subjects and 10 cases of chronic duodenal ulcer patients. Pretreatment with propranolol produced a signigicant depression of the 90 minute acid response to histamine in both volume and acidity in normals and duodenal ulcer cases. It is concluded that propranolol has an antisecretory effect, not only on basal gastric secretion but also on histamine stimulated secretion in man. Reserpine stimulated gastric acid secretion and volume in normals but showed no similar effect in D.U. cases. After pretreatment with propranolol it reduces the gastric acid secretion and volume in normals and D.U. cases."} {"id": "PMID:1264476", "title": "A cervical spinal cord injury following chiropractic manipulation.", "content": "A case is presented of a permanent C4 tetraplegia following chiropractic manipulation of a patient with ankylosing spondylitis. The pertinent literature is reviewed.", "contents": "A cervical spinal cord injury following chiropractic manipulation. A case is presented of a permanent C4 tetraplegia following chiropractic manipulation of a patient with ankylosing spondylitis. The pertinent literature is reviewed."} {"id": "PMID:1264477", "title": "Urological management in onon-traumatic paraplegia: disc protrusions, multiple sclerosis and spinal metastases.", "content": "The urological management in non-traumatic paraplegia differs little from the management of the traumatic case; a policy of conservative optimism is adopted, particularly in dealing with multiple sclerosis and certain malignancies.", "contents": "Urological management in onon-traumatic paraplegia: disc protrusions, multiple sclerosis and spinal metastases. The urological management in non-traumatic paraplegia differs little from the management of the traumatic case; a policy of conservative optimism is adopted, particularly in dealing with multiple sclerosis and certain malignancies."} {"id": "PMID:1264478", "title": "Micturition patterns in patients paraplegic following spinal cord injury.", "content": "Patterns of micturition in normal subjects and in patients after complete and incomplete injury of the spinal cord have been compared. All patients showed an abnormal flow pattern, this being least obvious in those who had undergone resection of the bladder neck and external sphincter. It is suggested that the Disa type 14 F 45 mictiograph is a useful instrument in determining the need for transurethral resection following spinal cord injury.", "contents": "Micturition patterns in patients paraplegic following spinal cord injury. Patterns of micturition in normal subjects and in patients after complete and incomplete injury of the spinal cord have been compared. All patients showed an abnormal flow pattern, this being least obvious in those who had undergone resection of the bladder neck and external sphincter. It is suggested that the Disa type 14 F 45 mictiograph is a useful instrument in determining the need for transurethral resection following spinal cord injury."} {"id": "PMID:1264479", "title": "A further look at the rationale of 'external sphincterotomy'.", "content": "A sound anatomical and physiological basis has now been provided for the endoscopic operations which are carried out for the relief of urethral obstruction due to spasticity of the external sphincter. However, the operation 'external sphincterotomy' was originally applied empirically to cases with sacral areflexia in which the mechanism of the obstruction was obscure. It now seems that plain muscle contraction under sympathetic control and influenced by posture is probably responsible and there are prospects of relief from the use of alpha-adrenergic blocking agents. When endoscopic incision is required, the operation might be better designated 'internal membranous urethrotomy'.", "contents": "A further look at the rationale of 'external sphincterotomy'. A sound anatomical and physiological basis has now been provided for the endoscopic operations which are carried out for the relief of urethral obstruction due to spasticity of the external sphincter. However, the operation 'external sphincterotomy' was originally applied empirically to cases with sacral areflexia in which the mechanism of the obstruction was obscure. It now seems that plain muscle contraction under sympathetic control and influenced by posture is probably responsible and there are prospects of relief from the use of alpha-adrenergic blocking agents. When endoscopic incision is required, the operation might be better designated 'internal membranous urethrotomy'."} {"id": "PMID:1264480", "title": "Modified approach to sphincterotomy in spinal cord injury patients. Indications, technique and results in 32 patients.", "content": "Indications, technique and results of a modified approach to an extended sphincterotomy in spinal cord injury patients with voiding dysfunctions is presented. There were 32 patients who underwent surgery and were subjected to analysis for their dysfunctional bladder and bladder-neck problems. Overall satisfactory results were obtained in about 90 per cent patients following sphincterotomy. Early recognition of patients where intermittent catheterisation may not succeed is presented to intervene and establish an early catheter-free status in such patients. Foley indwelling catheter in ten patients, being worn from seven months to four years, where intermittent catheterisation had not succeeded elsewhere, were decatheterised following surgery. Excellent results were obtained in ten patients with vesico-urethral reflux; external sphincterotomy, therefore, seems to be the treatment of choice for complete spinal cord transection with vesico-ureteral reflux. An attempt has also been made to present physiology of micturition reflex in spinal cord injury patients.", "contents": "Modified approach to sphincterotomy in spinal cord injury patients. Indications, technique and results in 32 patients. Indications, technique and results of a modified approach to an extended sphincterotomy in spinal cord injury patients with voiding dysfunctions is presented. There were 32 patients who underwent surgery and were subjected to analysis for their dysfunctional bladder and bladder-neck problems. Overall satisfactory results were obtained in about 90 per cent patients following sphincterotomy. Early recognition of patients where intermittent catheterisation may not succeed is presented to intervene and establish an early catheter-free status in such patients. Foley indwelling catheter in ten patients, being worn from seven months to four years, where intermittent catheterisation had not succeeded elsewhere, were decatheterised following surgery. Excellent results were obtained in ten patients with vesico-urethral reflux; external sphincterotomy, therefore, seems to be the treatment of choice for complete spinal cord transection with vesico-ureteral reflux. An attempt has also been made to present physiology of micturition reflex in spinal cord injury patients."} {"id": "PMID:1264481", "title": "The twelve o'clock sphincterotomy: technique, indications, results.", "content": "Outflow obstruction at the level of the external sphincter in patients with neurogenic bladder dysfunction is common and transurethral sphincterotomy the treatment of choice. Based upon the anatomy of the striated muscle fibres forming the external sphincter and its blood supply, we find from our results on 35 patients, 17 of whom had a follow-up of more than three years, a transurethral sphincterotomy only in the 12 o'clock position as sufficient and preferable. The results indicate that this comparatively simple technique is effective in order to diminish outflow resistance at the level of the membranous urethra. Concerning fresh paraplegics with unbalanced reflex bladder, sphincterotomy is usually not performed earlier than one year after the injury.", "contents": "The twelve o'clock sphincterotomy: technique, indications, results. Outflow obstruction at the level of the external sphincter in patients with neurogenic bladder dysfunction is common and transurethral sphincterotomy the treatment of choice. Based upon the anatomy of the striated muscle fibres forming the external sphincter and its blood supply, we find from our results on 35 patients, 17 of whom had a follow-up of more than three years, a transurethral sphincterotomy only in the 12 o'clock position as sufficient and preferable. The results indicate that this comparatively simple technique is effective in order to diminish outflow resistance at the level of the membranous urethra. Concerning fresh paraplegics with unbalanced reflex bladder, sphincterotomy is usually not performed earlier than one year after the injury."} {"id": "PMID:1264482", "title": "Late results of bilateral endoscopic sphincterotomy in patients with upper motor neurone lesions.", "content": "Most authors presently agree that in motor neurone lesions sphincterotomy provides a reliable means of alleviating chronic retention due to detrusor-sphincter dysfunction. But, although early results may be very encouraging, one should consider that some patients are prone to fibro-sclerotic restenosis. Regular annual check-ups are therefore essential in order to avoid relevant complications.", "contents": "Late results of bilateral endoscopic sphincterotomy in patients with upper motor neurone lesions. Most authors presently agree that in motor neurone lesions sphincterotomy provides a reliable means of alleviating chronic retention due to detrusor-sphincter dysfunction. But, although early results may be very encouraging, one should consider that some patients are prone to fibro-sclerotic restenosis. Regular annual check-ups are therefore essential in order to avoid relevant complications."} {"id": "PMID:1264483", "title": "Pathology of the striated urethral sphincter in spinal cord injury patients: indications and results of external sphincterotomy (100 cases).", "content": "Up to date, we have carried out 100 external sphincterotomies, of which 65 only concerned traumatic spinal cord injuries.", "contents": "Pathology of the striated urethral sphincter in spinal cord injury patients: indications and results of external sphincterotomy (100 cases). Up to date, we have carried out 100 external sphincterotomies, of which 65 only concerned traumatic spinal cord injuries."} {"id": "PMID:1264484", "title": "Differential diagnosis and limitations of external sphincterotomy.", "content": "A study of 1000 neurologic bladders has shown us that a well-balanced working of the bladder must be keenly searched for, and that sphincterotomy must be early indicated, and even performed several times if necessary. So 100 sphincterotomies performed on male patients, out of 730 cases, have shown us that their one-and-only risk, incontinence, depended chiefly of the condition of the detrusor, therefore on the short or long evolution of the sclerosis of the external sphincter, which is only one out of all the possible impediments.", "contents": "Differential diagnosis and limitations of external sphincterotomy. A study of 1000 neurologic bladders has shown us that a well-balanced working of the bladder must be keenly searched for, and that sphincterotomy must be early indicated, and even performed several times if necessary. So 100 sphincterotomies performed on male patients, out of 730 cases, have shown us that their one-and-only risk, incontinence, depended chiefly of the condition of the detrusor, therefore on the short or long evolution of the sclerosis of the external sphincter, which is only one out of all the possible impediments."} {"id": "PMID:1264485", "title": "The effect of trans-urethral surgery on penile erections in spinal cord injury patients.", "content": "The effect of transurethral surgery on penile erections in 62 spinal cord injury patients is reviewed. In a group of 43 patients with preoperative erections, 19 noticed no change in the pattern of erections. Twenty-four of the 43 patients notice either a diminution or total disappearance.", "contents": "The effect of trans-urethral surgery on penile erections in spinal cord injury patients. The effect of transurethral surgery on penile erections in 62 spinal cord injury patients is reviewed. In a group of 43 patients with preoperative erections, 19 noticed no change in the pattern of erections. Twenty-four of the 43 patients notice either a diminution or total disappearance."} {"id": "PMID:1264486", "title": "Impairment of erection after external sphincter resection.", "content": "Two cases of temporary loss of reflex erectile activity after transurethral bladder-neck and external sphincter resection are reported in two tetraplegics. Only recently such occurrences have been reported in the literature associated with external sphincterotomy. The reasons are discussed and most likely direct damage to erectile tissues is the cause of such a complication.", "contents": "Impairment of erection after external sphincter resection. Two cases of temporary loss of reflex erectile activity after transurethral bladder-neck and external sphincter resection are reported in two tetraplegics. Only recently such occurrences have been reported in the literature associated with external sphincterotomy. The reasons are discussed and most likely direct damage to erectile tissues is the cause of such a complication."} {"id": "PMID:1264487", "title": "Experiments with defined multispecific coccidial infections in lambs.", "content": "The behaviour of four species of Eimeria was studied in lambs which were given either monospecific or multispecific infections. In the presence of other species the patency of oocyst production of E. ovina and E. weybridgensis was extended and the total number of oocysts produced by all species except E. ninakohlyakimovae was increased. Clinical symptoms were observed only in lambs which received E. ninakohlyakimovae.", "contents": "Experiments with defined multispecific coccidial infections in lambs. The behaviour of four species of Eimeria was studied in lambs which were given either monospecific or multispecific infections. In the presence of other species the patency of oocyst production of E. ovina and E. weybridgensis was extended and the total number of oocysts produced by all species except E. ninakohlyakimovae was increased. Clinical symptoms were observed only in lambs which received E. ninakohlyakimovae."} {"id": "PMID:1264488", "title": "A study on snail location by Fasciola hepatica using radioisotopically labelled miracidia.", "content": "A number of common freshwater molluscs were exposed to Fasciola hepatica miracidia labelled in vivo with radioselenium. Radioactivity was rapidly incorporated in all lymnaeid species tested (L. stagnalis, L. tomentosa and L. truncatula) whereas no radioactivity could be demonstrated in non-lymnaeid pulmonate species (Aplexa hypnorum, Physa acuta, Physa fontinalis, Anisus vortex, Gyraulus albus and Planorbis planorbis) or in the prosobranchs Valvata cristata and Valvata piscinalis. However, the prosobranchs Bithynia leachii, Bithynia tentaculata and Potamopyrgus jenkinsi showed a slow but significant uptake of radioactivity which was presumably explained by uptake of labelled miracidia through a 'filter-feeding' mechanism. Sphaerium corneum, a true filter-feeder, showed a similar course of uptake of radioactivity.", "contents": "A study on snail location by Fasciola hepatica using radioisotopically labelled miracidia. A number of common freshwater molluscs were exposed to Fasciola hepatica miracidia labelled in vivo with radioselenium. Radioactivity was rapidly incorporated in all lymnaeid species tested (L. stagnalis, L. tomentosa and L. truncatula) whereas no radioactivity could be demonstrated in non-lymnaeid pulmonate species (Aplexa hypnorum, Physa acuta, Physa fontinalis, Anisus vortex, Gyraulus albus and Planorbis planorbis) or in the prosobranchs Valvata cristata and Valvata piscinalis. However, the prosobranchs Bithynia leachii, Bithynia tentaculata and Potamopyrgus jenkinsi showed a slow but significant uptake of radioactivity which was presumably explained by uptake of labelled miracidia through a 'filter-feeding' mechanism. Sphaerium corneum, a true filter-feeder, showed a similar course of uptake of radioactivity."} {"id": "PMID:1264489", "title": "Immunity to primary and challenge infections of Trichinella spiralis in mice: a re-examination of conventional parameters.", "content": "In young (6- to 8-week-old) NIH strain inbred mice expulsion of a primary infection of Trichinella spiralis began on day 8 and was virtually complete by day 11-5. In older mice expulsion occurred 1 or 2 days earlier. Experience of a primary infection elicited strong immunity to challenge, whether the challenge was given immediately after worm expulsion (day 14) or delayed (day 42). Challenge infections were expelled rapidly the majority of worms being lost during the first day. Immunity to challenge was elicited by low-level primary infections and was effective against large ventionally accepted parameters of immunity to T. spiralis in mice which, it is considered, are applicable only to mice with a genetically determined low-level of responsiveness to the parasite.", "contents": "Immunity to primary and challenge infections of Trichinella spiralis in mice: a re-examination of conventional parameters. In young (6- to 8-week-old) NIH strain inbred mice expulsion of a primary infection of Trichinella spiralis began on day 8 and was virtually complete by day 11-5. In older mice expulsion occurred 1 or 2 days earlier. Experience of a primary infection elicited strong immunity to challenge, whether the challenge was given immediately after worm expulsion (day 14) or delayed (day 42). Challenge infections were expelled rapidly the majority of worms being lost during the first day. Immunity to challenge was elicited by low-level primary infections and was effective against large ventionally accepted parameters of immunity to T. spiralis in mice which, it is considered, are applicable only to mice with a genetically determined low-level of responsiveness to the parasite."} {"id": "PMID:1264490", "title": "A genetic investigation of virulence in a rodent malaria parasite.", "content": "The genetic basis of virulence in a line (YM) of Plasmodium yoelii yoelii was investigated in a cross with a mild line (A/C). The blood forms of the virulent line developed extensively in mature erythrocytes of mice, causing death of the host within 7 days; infections with the mild line were normally restricted to reticulocytes, infected animals recovering after three weeks. Lines YM and A/C differed additionally in enzyme and drug-sensitivity markers. Studies on infections established from each line alone from sporozoite mixtures of the two lines and from the cross between the lines showed that the appearance of virulence had been caused by a genetic change in the parasite, and not by other factors such as a concurrent infection with another organism. An analysis of the characters of 56 clones derived from the cross showed that the virulence character had undergone recombination with the other markers, and appeared to be inherited in Mendelian fashion. Three clones exhibited atypical virulence, although it was not clear whether this had been produced by genetic recombination.", "contents": "A genetic investigation of virulence in a rodent malaria parasite. The genetic basis of virulence in a line (YM) of Plasmodium yoelii yoelii was investigated in a cross with a mild line (A/C). The blood forms of the virulent line developed extensively in mature erythrocytes of mice, causing death of the host within 7 days; infections with the mild line were normally restricted to reticulocytes, infected animals recovering after three weeks. Lines YM and A/C differed additionally in enzyme and drug-sensitivity markers. Studies on infections established from each line alone from sporozoite mixtures of the two lines and from the cross between the lines showed that the appearance of virulence had been caused by a genetic change in the parasite, and not by other factors such as a concurrent infection with another organism. An analysis of the characters of 56 clones derived from the cross showed that the virulence character had undergone recombination with the other markers, and appeared to be inherited in Mendelian fashion. Three clones exhibited atypical virulence, although it was not clear whether this had been produced by genetic recombination."} {"id": "PMID:1264491", "title": "The sites occupied by the acanthocephalan Pomphorhynchus laevis in the alimentary canal of fish.", "content": "The distribution of the acanthocephalan Pomphorhynchus laevis along the alimentary tract of several species of freshwaster fish was studied in both natural and experimental infections. The parasite exhibits a clear preference for a particular region of the alimentary canal, which differs from host species to host species, but it is capable of surviving in all regions of the intestine. In some species, but not in all, its growth rate may be reduced in regions outside of the preferred site. The parsite remains in the same site throughout the period of infection, emigrations occurring only preparatory to complete loss of the parasite from the host. The presence of cestodes in the region of the preferred site has no effect upon the distribution of the parasite. At high levels of infection the range of the parsite's distribution is extended. The feeding of larval parasites to fish by stomach tube also leads to an extension of range, whereas when fish are allowed to feed on cystacanths removed from their intermediate host the parasite establishes in a more anterior position than usual and in a site that it does not occupy to any extent in natural infections. It is concluded that the distribution of P. laevis in the alimentary canal of fish is determined primarily by the process of liberation, activation and establishment of the parasite, and that it normally attaches in the first available space and remains there. Unsuitable physico-chemical or feeding conditions affect only its growth, not the site that it occupies. It is suggested that P. laevis may be atypical in this respect.", "contents": "The sites occupied by the acanthocephalan Pomphorhynchus laevis in the alimentary canal of fish. The distribution of the acanthocephalan Pomphorhynchus laevis along the alimentary tract of several species of freshwaster fish was studied in both natural and experimental infections. The parasite exhibits a clear preference for a particular region of the alimentary canal, which differs from host species to host species, but it is capable of surviving in all regions of the intestine. In some species, but not in all, its growth rate may be reduced in regions outside of the preferred site. The parsite remains in the same site throughout the period of infection, emigrations occurring only preparatory to complete loss of the parasite from the host. The presence of cestodes in the region of the preferred site has no effect upon the distribution of the parasite. At high levels of infection the range of the parsite's distribution is extended. The feeding of larval parasites to fish by stomach tube also leads to an extension of range, whereas when fish are allowed to feed on cystacanths removed from their intermediate host the parasite establishes in a more anterior position than usual and in a site that it does not occupy to any extent in natural infections. It is concluded that the distribution of P. laevis in the alimentary canal of fish is determined primarily by the process of liberation, activation and establishment of the parasite, and that it normally attaches in the first available space and remains there. Unsuitable physico-chemical or feeding conditions affect only its growth, not the site that it occupies. It is suggested that P. laevis may be atypical in this respect."} {"id": "PMID:1264516", "title": "Considerations in management of the child with cerebral palsy.", "content": "Throughout this article, the reader will recognize that the term \"management\" rather than \"treatment\" has been used when referring to the child with cerebral palsy. Treatment implies a reasonable chance for cure, something that is currently impossible in cerebral palsy. \"Management\" is a more honest term, implying consideration of all of the problems of the child with cerebral palsy and his family and bringing to bear those elements of decision making that lead to maximal benefit to the patient.", "contents": "Considerations in management of the child with cerebral palsy. Throughout this article, the reader will recognize that the term \"management\" rather than \"treatment\" has been used when referring to the child with cerebral palsy. Treatment implies a reasonable chance for cure, something that is currently impossible in cerebral palsy. \"Management\" is a more honest term, implying consideration of all of the problems of the child with cerebral palsy and his family and bringing to bear those elements of decision making that lead to maximal benefit to the patient."} {"id": "PMID:1264518", "title": "Primary recognition and treatment of congenital dislocation of the hip.", "content": "The pathology associated with congenital dislocation of the hip has been reviewed. The pathophysiology as it affects the development of the hip under treatment makes a strong case for the avoidance of the \"frog leg\" position with fixed flexion and abduction of the hips in the plaster cast. It is apparent that tightness of the iliopsoas muscle and the underlying capsule makes that flexed abduction position necessary to hold the hip in position. The \"frog leg\" position is seriously implicated in the development of aseptic necrosis, not only of the dislocated hip but of the normal hip as well. The results seen in patients with surgical division of the iliopsoas tendon and capsular contracture, followed by leg immobilization in a functional position of extension at the hip accompanied by slight abduction and internal rotation, indicate the virtual elimination of the necessity for secondary reconstruction procedures on the hip at a later date. This appears to be the more conservative approach to treatment in children under age two. A period of one to three months in a splint that flexes and abducts the leg but permits changing positons may be tried before the obstruction is relieved. For children with lax capsule and iliopsoas, reduction may be possible by this route. For most the hip will be pressed in slightly improving the x-ray picture--but with the obstruction still before the femoral head. The seating of the femoral head must be exact. If it is not, imperfection in the development of the hip arises and may lead to later malfunction. Obstructions to perfect seating of the femoral head in the acetabulum must be overcome.", "contents": "Primary recognition and treatment of congenital dislocation of the hip. The pathology associated with congenital dislocation of the hip has been reviewed. The pathophysiology as it affects the development of the hip under treatment makes a strong case for the avoidance of the \"frog leg\" position with fixed flexion and abduction of the hips in the plaster cast. It is apparent that tightness of the iliopsoas muscle and the underlying capsule makes that flexed abduction position necessary to hold the hip in position. The \"frog leg\" position is seriously implicated in the development of aseptic necrosis, not only of the dislocated hip but of the normal hip as well. The results seen in patients with surgical division of the iliopsoas tendon and capsular contracture, followed by leg immobilization in a functional position of extension at the hip accompanied by slight abduction and internal rotation, indicate the virtual elimination of the necessity for secondary reconstruction procedures on the hip at a later date. This appears to be the more conservative approach to treatment in children under age two. A period of one to three months in a splint that flexes and abducts the leg but permits changing positons may be tried before the obstruction is relieved. For children with lax capsule and iliopsoas, reduction may be possible by this route. For most the hip will be pressed in slightly improving the x-ray picture--but with the obstruction still before the femoral head. The seating of the femoral head must be exact. If it is not, imperfection in the development of the hip arises and may lead to later malfunction. Obstructions to perfect seating of the femoral head in the acetabulum must be overcome."} {"id": "PMID:1264519", "title": "Diagnosis and management of torticollis.", "content": "Clearly, torticollis may stem from a variety of factors involving a number of primary structures -- bones, ligaments, muscles, and the nervous system. The crucial point is to differentiate torticollis that may lead to structural changes from that of a compensatory or functional nature. The key criterion is whether torticollis persists or resolves. This can be readily determined by treating torticollis initially with head halter traction of three to four pounds' weight and observing whether it resolves in five of seven days. If the torticollis and related symptoms persist beyond this time, the physician should consider possible lesions other than common rotary subluxation. Diagnosis of unresolved torticollis requires extensive and often repetitive investigation procedures. Perseverance in the diagnosis and management of persistent torticollis is a commendable virtue.", "contents": "Diagnosis and management of torticollis. Clearly, torticollis may stem from a variety of factors involving a number of primary structures -- bones, ligaments, muscles, and the nervous system. The crucial point is to differentiate torticollis that may lead to structural changes from that of a compensatory or functional nature. The key criterion is whether torticollis persists or resolves. This can be readily determined by treating torticollis initially with head halter traction of three to four pounds' weight and observing whether it resolves in five of seven days. If the torticollis and related symptoms persist beyond this time, the physician should consider possible lesions other than common rotary subluxation. Diagnosis of unresolved torticollis requires extensive and often repetitive investigation procedures. Perseverance in the diagnosis and management of persistent torticollis is a commendable virtue."} {"id": "PMID:1264520", "title": "Childhood foot and leg problems.", "content": "A thorough history and examination are essential to the accurate diagnosis of foot and leg problems in children. Most such problems, if diagnosed and treated early, can be corrected by conservative measures. Footwear for these children must be properly chosen.", "contents": "Childhood foot and leg problems. A thorough history and examination are essential to the accurate diagnosis of foot and leg problems in children. Most such problems, if diagnosed and treated early, can be corrected by conservative measures. Footwear for these children must be properly chosen."} {"id": "PMID:1264521", "title": "Orthopedic overview of juvenile rheumatoid arthritis.", "content": "Juvenile rheumatoid arthritis can be classified into three forms by the extent of early involvement: (1) pauciarticular, (2) polyarticular, and (3) systemic. When this disease, in which remission is common, is properly diagnosed and appropriately treated by physical therapy, occupational therapy, drug therapy, and surgical treatment, a good clinical result can usually be expected. Only 16 of 124 children had severe persistent impairment because of the disease in one recent study;18 this number may be high, since mild cases may be unrecognized or not be referred to the study clinic. However, efforts should be directed to reducing this number of severely impaired children -- in the short run by better techniques of reconstructive surgery and in the long run by a better understanding, through research into the etiology and pathogenesis of the disease adequate to prevent or significantly alter its course. The disease may be caused by a treatable occult infective agent and may respond to an approach similar to that for rheumatic fever, which no longer fills the wards of our children's hospitals as it once did.", "contents": "Orthopedic overview of juvenile rheumatoid arthritis. Juvenile rheumatoid arthritis can be classified into three forms by the extent of early involvement: (1) pauciarticular, (2) polyarticular, and (3) systemic. When this disease, in which remission is common, is properly diagnosed and appropriately treated by physical therapy, occupational therapy, drug therapy, and surgical treatment, a good clinical result can usually be expected. Only 16 of 124 children had severe persistent impairment because of the disease in one recent study;18 this number may be high, since mild cases may be unrecognized or not be referred to the study clinic. However, efforts should be directed to reducing this number of severely impaired children -- in the short run by better techniques of reconstructive surgery and in the long run by a better understanding, through research into the etiology and pathogenesis of the disease adequate to prevent or significantly alter its course. The disease may be caused by a treatable occult infective agent and may respond to an approach similar to that for rheumatic fever, which no longer fills the wards of our children's hospitals as it once did."} {"id": "PMID:1264537", "title": "The effect of age, sex, race, and economic status on dental caries experience of the permanent dentition. Committee to Review the Ten-State Nutrition Survey of 1968-1970.", "content": "The Ten-State Nutrition Survey data show a consistent, dramatic, and meaningful difference in dental caries experience between black and white children at all ages. This difference transcends socioeconomic grouping, nutritional level, and developmental status. This study also has shown an apparently protective effect of poverty insofar as dental caries is concerned. Children from lower-income families experienced less dental caries than children from higher-income families.", "contents": "The effect of age, sex, race, and economic status on dental caries experience of the permanent dentition. Committee to Review the Ten-State Nutrition Survey of 1968-1970. The Ten-State Nutrition Survey data show a consistent, dramatic, and meaningful difference in dental caries experience between black and white children at all ages. This difference transcends socioeconomic grouping, nutritional level, and developmental status. This study also has shown an apparently protective effect of poverty insofar as dental caries is concerned. Children from lower-income families experienced less dental caries than children from higher-income families."} {"id": "PMID:1264541", "title": "Birthweight doubling time: a fresh look.", "content": "Infant birthweight doubling time is widely quoted as being achieved between 5 and 6 months. The purpose of this study was to determine the time of birthweight doubling and to identify important related variables. A total of 357 normal infants with birthweights between 2,500 and 4,100 gm were studied. Mean age of birthweight doubling for the entire group was 119 days (3.8 months). Bottle-fed infants doubled their birthweights earlier than breast-fed infants: 113 days vs. 124 days (P less than .05). Boys doubled their birthweights earlier than girls: 111 days vs. 129 days (P less than .0001). Solids were introduced earlier in bottle-fed infants (mean , 1.9 months) than in breast-fed infants (mean, 3.9 months). Harvard percentiles for mean group weight and length at the time of birthweight doubling were: for bottle-fed infants, 75th and 55th percentiles respectively: for breast-fed infants, 55th and 60th percentiles respectively; for boys, 75th percentile for both weight and length; for girls, 50th percentile for both weight and length. Thus, bottle-fed infants appear to have weight gains in excess of length gain and may be developing early obesity. In light of the poor prognosis in treating obesity, closer supervision of early infant feeding practices is indicated.", "contents": "Birthweight doubling time: a fresh look. Infant birthweight doubling time is widely quoted as being achieved between 5 and 6 months. The purpose of this study was to determine the time of birthweight doubling and to identify important related variables. A total of 357 normal infants with birthweights between 2,500 and 4,100 gm were studied. Mean age of birthweight doubling for the entire group was 119 days (3.8 months). Bottle-fed infants doubled their birthweights earlier than breast-fed infants: 113 days vs. 124 days (P less than .05). Boys doubled their birthweights earlier than girls: 111 days vs. 129 days (P less than .0001). Solids were introduced earlier in bottle-fed infants (mean , 1.9 months) than in breast-fed infants (mean, 3.9 months). Harvard percentiles for mean group weight and length at the time of birthweight doubling were: for bottle-fed infants, 75th and 55th percentiles respectively: for breast-fed infants, 55th and 60th percentiles respectively; for boys, 75th percentile for both weight and length; for girls, 50th percentile for both weight and length. Thus, bottle-fed infants appear to have weight gains in excess of length gain and may be developing early obesity. In light of the poor prognosis in treating obesity, closer supervision of early infant feeding practices is indicated."} {"id": "PMID:1264542", "title": "A therapeutic trial of fatty acid supplementation in cystic fibrosis.", "content": "Seven children with cystic fibrosis (CF) have been treated for at least one year with intravenously administered soya oil emulsion. In all, an improvement of at least one biochemical abnormality in character with the disease appeared. The children's clinical course remains benign. This course is remarkably better than that of other children with CF treated without Intralipid in Auckland in the same period, though a placebo effect cannot be discounted. It is postulated that intravenous supplementation with essential fatty acid in CF may in turn partially correct an error of metabolism of prostaglandins present in the disease.", "contents": "A therapeutic trial of fatty acid supplementation in cystic fibrosis. Seven children with cystic fibrosis (CF) have been treated for at least one year with intravenously administered soya oil emulsion. In all, an improvement of at least one biochemical abnormality in character with the disease appeared. The children's clinical course remains benign. This course is remarkably better than that of other children with CF treated without Intralipid in Auckland in the same period, though a placebo effect cannot be discounted. It is postulated that intravenous supplementation with essential fatty acid in CF may in turn partially correct an error of metabolism of prostaglandins present in the disease."} {"id": "PMID:1264543", "title": "Abnormal fatty acid composition and impaired oxygen supply in cystic fibrosis patients.", "content": "Impaired oxygen supply and deteriorating health, in cystic fibrosis patients, correlates with abnormal changes in the fatty acid composition of blood lipids. As the proportion of oleates increases and that of linoleates decreases, erythrocyte membrane interference with the formation of intracellular oxyhemoglobin increases and arterial oxygen pressure decreases. The physical-chemical basis for these changes seems to be that oleic and linoleic acid differ in their ability to undergo reversible oxygenation in response to changes in oxygen pressure. The oxygen complex of linoleic acid dissociates at relatively high pressures, whereas that of oleic dissociates only at low pressures. Accordingly, excessive substitution of oleic for linoleic acid in membrane lipids would be expected to decrease the intracellular oxygen pressure to a level where hemoglobin oxygenation and any other oxygen-requiring processes would be impaired.", "contents": "Abnormal fatty acid composition and impaired oxygen supply in cystic fibrosis patients. Impaired oxygen supply and deteriorating health, in cystic fibrosis patients, correlates with abnormal changes in the fatty acid composition of blood lipids. As the proportion of oleates increases and that of linoleates decreases, erythrocyte membrane interference with the formation of intracellular oxyhemoglobin increases and arterial oxygen pressure decreases. The physical-chemical basis for these changes seems to be that oleic and linoleic acid differ in their ability to undergo reversible oxygenation in response to changes in oxygen pressure. The oxygen complex of linoleic acid dissociates at relatively high pressures, whereas that of oleic dissociates only at low pressures. Accordingly, excessive substitution of oleic for linoleic acid in membrane lipids would be expected to decrease the intracellular oxygen pressure to a level where hemoglobin oxygenation and any other oxygen-requiring processes would be impaired."} {"id": "PMID:1264544", "title": "Computer-assisted newborn intensive care.", "content": "A minicomputer has been programmed to aid in the intensive care of high-risk newborn babies. The computer provides 24-hour on-line access to physiologic and environmental data and controls the heating of infant incubators. The control algorithm limits fluctuations in the incubator chamber and protects the infant against escape from neutral thermal conditions. The mortality rate for 105 infants cared for using the computerized systems was significantly reduced when compared to that of 105 matched high-risk infants cared for using standard non-computer-assisted techniques in the same nursery setting.", "contents": "Computer-assisted newborn intensive care. A minicomputer has been programmed to aid in the intensive care of high-risk newborn babies. The computer provides 24-hour on-line access to physiologic and environmental data and controls the heating of infant incubators. The control algorithm limits fluctuations in the incubator chamber and protects the infant against escape from neutral thermal conditions. The mortality rate for 105 infants cared for using the computerized systems was significantly reduced when compared to that of 105 matched high-risk infants cared for using standard non-computer-assisted techniques in the same nursery setting."} {"id": "PMID:1264545", "title": "Importance of radiant flux in the treatment of hyperbilirubinemia: failure of overhead phototherapy units in intensive care units.", "content": "Prior to 1972, radiation used to treat neonatal hyperbilirubinemia was based upon the photometric unit, the foot-candle, a measure of light illumination. Measurements in terms of microwatts per square centimeter for selective wavelengths is more precise. We compared the effectiveness of phototherapy provided by overhead phototherapy units in intensive care modules vs. conventional phototherapy units. Forty-two infants were studied over a six-month period and divided into three groups based upon radiant flux measurements as follows: Group 1 (No. = 6), 1.0 muw to 1.9 muw/sq cm/nm; group 2 (No. = 15), 2.0 muw to 3.9 muw/sq cm/nm; group 3 (No. = 21), 4.0 muw to 6.0 muw/sq cm/nm. All flux determinations were made within the 400- to 500-nm range. All infants in group 1 were treated with overhead phototherapy units in the intensive care modules. Because of multiple factors known to increase the risk of kernicterus, evaluation of effectiveness of phototherapy at low radiant flux was limited in group 1. Significant changes in bilirubin were noted by 48 hours when comparing group 3 with groups 1 and 2. A minimum of 4.0 muw/sq cm/nm appears necessary for effective phototherapy. As designed, phototherapy units in intensive care modules are ineffective in delivering this therapeutic level of radiant flux.", "contents": "Importance of radiant flux in the treatment of hyperbilirubinemia: failure of overhead phototherapy units in intensive care units. Prior to 1972, radiation used to treat neonatal hyperbilirubinemia was based upon the photometric unit, the foot-candle, a measure of light illumination. Measurements in terms of microwatts per square centimeter for selective wavelengths is more precise. We compared the effectiveness of phototherapy provided by overhead phototherapy units in intensive care modules vs. conventional phototherapy units. Forty-two infants were studied over a six-month period and divided into three groups based upon radiant flux measurements as follows: Group 1 (No. = 6), 1.0 muw to 1.9 muw/sq cm/nm; group 2 (No. = 15), 2.0 muw to 3.9 muw/sq cm/nm; group 3 (No. = 21), 4.0 muw to 6.0 muw/sq cm/nm. All flux determinations were made within the 400- to 500-nm range. All infants in group 1 were treated with overhead phototherapy units in the intensive care modules. Because of multiple factors known to increase the risk of kernicterus, evaluation of effectiveness of phototherapy at low radiant flux was limited in group 1. Significant changes in bilirubin were noted by 48 hours when comparing group 3 with groups 1 and 2. A minimum of 4.0 muw/sq cm/nm appears necessary for effective phototherapy. As designed, phototherapy units in intensive care modules are ineffective in delivering this therapeutic level of radiant flux."} {"id": "PMID:1264546", "title": "Effects of phototherapy on platelet counts in low-birthweight infants and on platelet production and life span in rabbits.", "content": "The effects of conventional phototherapy on platelets in vivo were studied in rabbits and in low-birthweight infants. Rabbits were divided into three groups and individually treated continuously for 96 hours, with blue light, daylight, or no phototherapy. Incorporation of selenomethionine Se75 was used to evaluate platelet production and life span. Platelet turnover was significantly increased in the blue-light phototherapy group, and was also increased in the daylight group but to a lesser degree. Daily platelet counts and hematocrits were performed in infants weighing less than 2,000 gm at birth randomized at 24 +/- 12 hours of life to receive daylight phototherapy continuously for 96 hours (31 infants) or no phototherapy (26 infants). In 12 treated infants (38.7%) platelet counts fell below 150,000/cu mm whereas this occurred in only 3 (11.5%) of the controls. These two lower platelet count subgroups differed significantly in mean gestational age and birthweight with the phototherapy group being the more mature. Pre-phototherapy, the mean platelet count of these 12 infants was lower than the mean of the entire control group, suggesting that these infants had borderline marrow reserve before phototherapy was given. These results suggest that phototherapy increases the rate of platelet turnover. When bone marrow compensation is inadequate, the platelet count may fall.", "contents": "Effects of phototherapy on platelet counts in low-birthweight infants and on platelet production and life span in rabbits. The effects of conventional phototherapy on platelets in vivo were studied in rabbits and in low-birthweight infants. Rabbits were divided into three groups and individually treated continuously for 96 hours, with blue light, daylight, or no phototherapy. Incorporation of selenomethionine Se75 was used to evaluate platelet production and life span. Platelet turnover was significantly increased in the blue-light phototherapy group, and was also increased in the daylight group but to a lesser degree. Daily platelet counts and hematocrits were performed in infants weighing less than 2,000 gm at birth randomized at 24 +/- 12 hours of life to receive daylight phototherapy continuously for 96 hours (31 infants) or no phototherapy (26 infants). In 12 treated infants (38.7%) platelet counts fell below 150,000/cu mm whereas this occurred in only 3 (11.5%) of the controls. These two lower platelet count subgroups differed significantly in mean gestational age and birthweight with the phototherapy group being the more mature. Pre-phototherapy, the mean platelet count of these 12 infants was lower than the mean of the entire control group, suggesting that these infants had borderline marrow reserve before phototherapy was given. These results suggest that phototherapy increases the rate of platelet turnover. When bone marrow compensation is inadequate, the platelet count may fall."} {"id": "PMID:1264547", "title": "Compliance of chronic asthmatics with oral administration of theophylline as measured by serum and salivary levels.", "content": "A group of ambulatory asthmatic children was studied with serum and salivary theophylline levels following a prescribed dose of a hydroalcoholic solution of theophylline to determine compliance. The gas chromatographic procedure used was both selective and sensitive for theophylline without the necessity of withholding coffee, tea, chocolate, or cocoa. In the first group of patients, only 11% achieved therapeutic levels, 65% had less than therapeutic levels, and 23% had no measurable drug in saliva. With more directive and supervised drug administration in a second group of patients, 42% achieved therapeutic levels, 51% were below therapeutic levels, and only 6% had no measurable drug. Monitoring patients with salivary theophylline levels proved an effective way of improving compliance and also alerted physicians to noncompliance as a possible explanation of \"treatment failure\". Salivary specimens are readily obtained and noninvasive so that the technique is readily adaptable for use in the office of clinic setting.", "contents": "Compliance of chronic asthmatics with oral administration of theophylline as measured by serum and salivary levels. A group of ambulatory asthmatic children was studied with serum and salivary theophylline levels following a prescribed dose of a hydroalcoholic solution of theophylline to determine compliance. The gas chromatographic procedure used was both selective and sensitive for theophylline without the necessity of withholding coffee, tea, chocolate, or cocoa. In the first group of patients, only 11% achieved therapeutic levels, 65% had less than therapeutic levels, and 23% had no measurable drug in saliva. With more directive and supervised drug administration in a second group of patients, 42% achieved therapeutic levels, 51% were below therapeutic levels, and only 6% had no measurable drug. Monitoring patients with salivary theophylline levels proved an effective way of improving compliance and also alerted physicians to noncompliance as a possible explanation of \"treatment failure\". Salivary specimens are readily obtained and noninvasive so that the technique is readily adaptable for use in the office of clinic setting."} {"id": "PMID:1264548", "title": "Theophylline secretion into breast milk.", "content": "The infant of an asthmatic patient showed irritability associated with ingestion of breast milk only on days when the mother was taking theophylline. Pharmacokinetic studies in this woman and in four other subjects revealed that theophylline distributes well into breast milk. The average milk to serum concentration ratio of the drug was about 0.7 and milk concentrations paralleled the time-course of serum and saliva concentrations. On a relative body weight basis, a nursing infant would usually receive less than 10% of the mother's dose of theophylline which is normally an inconsequential amount.", "contents": "Theophylline secretion into breast milk. The infant of an asthmatic patient showed irritability associated with ingestion of breast milk only on days when the mother was taking theophylline. Pharmacokinetic studies in this woman and in four other subjects revealed that theophylline distributes well into breast milk. The average milk to serum concentration ratio of the drug was about 0.7 and milk concentrations paralleled the time-course of serum and saliva concentrations. On a relative body weight basis, a nursing infant would usually receive less than 10% of the mother's dose of theophylline which is normally an inconsequential amount."} {"id": "PMID:1264549", "title": "Relationship of allergy, enuresis, and urinary infection in children 4 to 7 years of age.", "content": "A group of 234 children, 4 to 7 years old, in a middle- to upper-middle-class Caucasian population, were divided into four groups and matched for age and sex. Group 1 consisted of 50 children previously treated for urinary infection: control group 1 contained 55 well children; group 2 consisted of 69 children treated for respiratory allergy; and control group 2 contained 60 well children. There was no statistical difference in persistent enuresis (night wetting every week), persistent day wetting (every week), allergy, or family history of enuresis, when group 1 and control group 1 were compared. A family history of urinary infection was higher (P less than .05) in group 1. There was no statistical difference in persistent enuresis, persistent day wetting, previous urinary infection, or family history of enuresis or urinary infection when group 2 and control group 2 were compared. This study suggests that there is no relationship between respiratory allergy, enuresis, and urinary infection.", "contents": "Relationship of allergy, enuresis, and urinary infection in children 4 to 7 years of age. A group of 234 children, 4 to 7 years old, in a middle- to upper-middle-class Caucasian population, were divided into four groups and matched for age and sex. Group 1 consisted of 50 children previously treated for urinary infection: control group 1 contained 55 well children; group 2 consisted of 69 children treated for respiratory allergy; and control group 2 contained 60 well children. There was no statistical difference in persistent enuresis (night wetting every week), persistent day wetting (every week), allergy, or family history of enuresis, when group 1 and control group 1 were compared. A family history of urinary infection was higher (P less than .05) in group 1. There was no statistical difference in persistent enuresis, persistent day wetting, previous urinary infection, or family history of enuresis or urinary infection when group 2 and control group 2 were compared. This study suggests that there is no relationship between respiratory allergy, enuresis, and urinary infection."} {"id": "PMID:1264550", "title": "Benign familial macrocephaly: report of a family and review of the literature.", "content": "Five members in two generations of one family were found to have occipitofrontal head circumferences more than 2 SD above the mean. All five had normal intelligence and neurological examinations. Three of the five had ventricular dilatation by A-mode echoencephalography. The inheritance pattern of macrocephaly in this family appears to be autosomal dominant with incomplete penetrance. Possible causes of the macrocephaly in this family are discussed and the reported cases of macrocephaly with normal intelligence and no neurological deficits are reviewed.", "contents": "Benign familial macrocephaly: report of a family and review of the literature. Five members in two generations of one family were found to have occipitofrontal head circumferences more than 2 SD above the mean. All five had normal intelligence and neurological examinations. Three of the five had ventricular dilatation by A-mode echoencephalography. The inheritance pattern of macrocephaly in this family appears to be autosomal dominant with incomplete penetrance. Possible causes of the macrocephaly in this family are discussed and the reported cases of macrocephaly with normal intelligence and no neurological deficits are reviewed."} {"id": "PMID:1264563", "title": "Congenital multicystic kidney.", "content": "By employing the three basic diagnostic modalities of uroradiology--intravenous urography, retrograde pyelography, angiography--an accurate radiological diagnosis can be made. Since congenital multicystic disease by definition is a nonfunctioning dysplastic kidney with an atretic or absent ureter and absent renal vasculature, these diagnostic methods are tailored precisely to demonstrate the specific characteristic functional and pathological features of congenital multicystic kidney disease. We find no function on intravenous urography, hypoplastic atretic ureter on retrograde pyelography, and an absent or hypoplastic renal artery indicated on angiography.", "contents": "Congenital multicystic kidney. By employing the three basic diagnostic modalities of uroradiology--intravenous urography, retrograde pyelography, angiography--an accurate radiological diagnosis can be made. Since congenital multicystic disease by definition is a nonfunctioning dysplastic kidney with an atretic or absent ureter and absent renal vasculature, these diagnostic methods are tailored precisely to demonstrate the specific characteristic functional and pathological features of congenital multicystic kidney disease. We find no function on intravenous urography, hypoplastic atretic ureter on retrograde pyelography, and an absent or hypoplastic renal artery indicated on angiography."} {"id": "PMID:1264564", "title": "Medullary sponge kidney.", "content": "\"Medullary sponge kidney\" applies to pathologically dilated collecting tubules within one or more renal pyramids of one or both kidneys, almost always diagnosed radiographically, of uncertain etiology, and presenting a clinical spectrum varying from an asymptomatic, incidental finding to severely complicating calcareous-infective disease, renal insufficiency, and death. Recognition of the characteristic urographic pattern affords the patient presenting clinically with hematuria, ureteral colic, urinary tract infection, or nephrocalcinosis a prompt diagnosis with a frequently benign prognosis, and usually averts more extensive or invasive investigations.", "contents": "Medullary sponge kidney. \"Medullary sponge kidney\" applies to pathologically dilated collecting tubules within one or more renal pyramids of one or both kidneys, almost always diagnosed radiographically, of uncertain etiology, and presenting a clinical spectrum varying from an asymptomatic, incidental finding to severely complicating calcareous-infective disease, renal insufficiency, and death. Recognition of the characteristic urographic pattern affords the patient presenting clinically with hematuria, ureteral colic, urinary tract infection, or nephrocalcinosis a prompt diagnosis with a frequently benign prognosis, and usually averts more extensive or invasive investigations."} {"id": "PMID:1264565", "title": "Juvenile nephronophthisis and renal medullary cystic disease.", "content": "In the past 30 years 238 cases have been published which describe the nephronophthisiscystic renal medulla complex. Of these, 110 are sufficiently adequate to permit detailed analyses. Both isolated and genetically transmitted cases are reported. The latter include the dominant and recessive modalities, both autosomal, and the former perhaps also X-linked. Renal disease also has been inherited as a recessive trait in association with retinal degeneration. Medullary cysts have been found in 73% of cases in which kidney tissue has been examined directly. Their presence seems to bear no relationship to the ability of involved kidneys to conserve sodium. Salt wasting is described in the presence and absence of medullary cysts. Techniques short of anatomic examination of the kidneys have rarely allowed cysts to be detected and diagnosis continues to rest on a high index of suspicion, aroused in turn by a positive family history for the disease. Arterial hypertension occurs in roughly one third of cases. Aminoaciduria is not a part of the syndrome. A defect in maximum urinary concentrating ability may be the best single early sign of involvement but data are scarce.", "contents": "Juvenile nephronophthisis and renal medullary cystic disease. In the past 30 years 238 cases have been published which describe the nephronophthisiscystic renal medulla complex. Of these, 110 are sufficiently adequate to permit detailed analyses. Both isolated and genetically transmitted cases are reported. The latter include the dominant and recessive modalities, both autosomal, and the former perhaps also X-linked. Renal disease also has been inherited as a recessive trait in association with retinal degeneration. Medullary cysts have been found in 73% of cases in which kidney tissue has been examined directly. Their presence seems to bear no relationship to the ability of involved kidneys to conserve sodium. Salt wasting is described in the presence and absence of medullary cysts. Techniques short of anatomic examination of the kidneys have rarely allowed cysts to be detected and diagnosis continues to rest on a high index of suspicion, aroused in turn by a positive family history for the disease. Arterial hypertension occurs in roughly one third of cases. Aminoaciduria is not a part of the syndrome. A defect in maximum urinary concentrating ability may be the best single early sign of involvement but data are scarce."} {"id": "PMID:1264566", "title": "Extrarenal manifestations of cystic kidney disease.", "content": "Cystic disorders of the kidney may manifest their presence not only through renal but also through systemic signs and symptoms. Extrarenal manifestations include cerebral aneurysms, hepatic cysts, hepatic fibrosis, polycythemia, and retinal changes. Awareness of such associations strengthens the likelihood that renal cystic disease will be detected in its earlier stages. Involvement of organs other than the kidneys takes on added significance as the lives of affected individuals are prolonged through dialysis and renal transplantation.", "contents": "Extrarenal manifestations of cystic kidney disease. Cystic disorders of the kidney may manifest their presence not only through renal but also through systemic signs and symptoms. Extrarenal manifestations include cerebral aneurysms, hepatic cysts, hepatic fibrosis, polycythemia, and retinal changes. Awareness of such associations strengthens the likelihood that renal cystic disease will be detected in its earlier stages. Involvement of organs other than the kidneys takes on added significance as the lives of affected individuals are prolonged through dialysis and renal transplantation."} {"id": "PMID:1264567", "title": "Normal development and experimental models of cystic renal disease.", "content": "From a review of renal development and experimental cystic disease, the following observations can be made: 1. The previous theories developed to explain cystic renal disease (nonunion, failure of regression, and obstruction to urine flow) do not adequately fit with the numerous recent observations made in studies of most experimental models or in human renal cystic disease. 2. The most acceptable theory to date for most types of renal cystic abnormalities (except those due to known obstruction of urine flow) is that abnormalities of the tubular supporting wall occur, probably as a result of toxic or metabolic injury to the tubular cells of the wall and the related interstitial tissues, which are exposed to the highest concentrations of these compounds. This theory would also help explain the etiology of cystic renal diseases in man and should lead to attempts to isolate toxic factors or enzyme abnormalities in susceptible families and in early cases. 3. Induction of cystic abnormalities through a variety of experimental manipulations and drugs reveals impressive strain, sex, and species variability, and these differences should be more carefully examined. 4. The same chemical that induces a cystic change in the mature, fully developed kidney may cause changes which are quite different (location, severity, etc.) in both the fetal and newborn kidney, in which continual nephrogenesis is occurring. 5. Many of the previous explanations of cystic changes require careful reinterpretation of the findings (to reconcile certain differences), and confirmatory studies should be performed to help piece together some of the puzzling observations noted, such as the cystic changes seen with adrenocorticosteroids, and their relationship to potassium depletion.", "contents": "Normal development and experimental models of cystic renal disease. From a review of renal development and experimental cystic disease, the following observations can be made: 1. The previous theories developed to explain cystic renal disease (nonunion, failure of regression, and obstruction to urine flow) do not adequately fit with the numerous recent observations made in studies of most experimental models or in human renal cystic disease. 2. The most acceptable theory to date for most types of renal cystic abnormalities (except those due to known obstruction of urine flow) is that abnormalities of the tubular supporting wall occur, probably as a result of toxic or metabolic injury to the tubular cells of the wall and the related interstitial tissues, which are exposed to the highest concentrations of these compounds. This theory would also help explain the etiology of cystic renal diseases in man and should lead to attempts to isolate toxic factors or enzyme abnormalities in susceptible families and in early cases. 3. Induction of cystic abnormalities through a variety of experimental manipulations and drugs reveals impressive strain, sex, and species variability, and these differences should be more carefully examined. 4. The same chemical that induces a cystic change in the mature, fully developed kidney may cause changes which are quite different (location, severity, etc.) in both the fetal and newborn kidney, in which continual nephrogenesis is occurring. 5. Many of the previous explanations of cystic changes require careful reinterpretation of the findings (to reconcile certain differences), and confirmatory studies should be performed to help piece together some of the puzzling observations noted, such as the cystic changes seen with adrenocorticosteroids, and their relationship to potassium depletion."} {"id": "PMID:1264568", "title": "The morphology of renal cystic disease.", "content": "The morphologic criteria that are applied to make distinctions among the cystic diseases of the kidney involve not the cyst itself but include rather the size, number, and distribution of cysts within the kidney(s); the site(s) along the nephron from which cysts arise; and the presence or absence of involvement in other organs. There continues to be a great need to subject these diseases to the utmost morphologic scrutiny, using all available techniques.", "contents": "The morphology of renal cystic disease. The morphologic criteria that are applied to make distinctions among the cystic diseases of the kidney involve not the cyst itself but include rather the size, number, and distribution of cysts within the kidney(s); the site(s) along the nephron from which cysts arise; and the presence or absence of involvement in other organs. There continues to be a great need to subject these diseases to the utmost morphologic scrutiny, using all available techniques."} {"id": "PMID:1264569", "title": "A classification of renal cysts.", "content": "Renal cysts are a heterogeneous group comprising heritable, developmental, and acquired disorders. The classification presented here has been developed, as have several others in the past, to incorporate radiographic, functional, and genetic contributions in its clinicopathologic correlations. Its major categories are as follows: (1) dysplastic cysts arising in kidneys that have undergone abnormal morphogenesis and differentiation; (2) polycystic disease of autosomal recessive and autosomal dominant types; (3) heritable syndromes of multiple malformations with renal cysts resulting from presumed metabolic injury; (4) isolated cortical cysts of unknown pathogenesis; (5) medullary cysts of several types, including medullary sponge kidney and the progressive syndromes of medullary cystic disease, familial juvenile nephronophthisis, and renal-retinal dysplasia; (6) acquired parenchymal cysts of diverse origins; and (7) extraparenchymal cysts. This classification, which has been revised repeatedly over the years, is still tentative and undoubtedly will be revised again.", "contents": "A classification of renal cysts. Renal cysts are a heterogeneous group comprising heritable, developmental, and acquired disorders. The classification presented here has been developed, as have several others in the past, to incorporate radiographic, functional, and genetic contributions in its clinicopathologic correlations. Its major categories are as follows: (1) dysplastic cysts arising in kidneys that have undergone abnormal morphogenesis and differentiation; (2) polycystic disease of autosomal recessive and autosomal dominant types; (3) heritable syndromes of multiple malformations with renal cysts resulting from presumed metabolic injury; (4) isolated cortical cysts of unknown pathogenesis; (5) medullary cysts of several types, including medullary sponge kidney and the progressive syndromes of medullary cystic disease, familial juvenile nephronophthisis, and renal-retinal dysplasia; (6) acquired parenchymal cysts of diverse origins; and (7) extraparenchymal cysts. This classification, which has been revised repeatedly over the years, is still tentative and undoubtedly will be revised again."} {"id": "PMID:1264570", "title": "Genetics in cystic kidney disease.", "content": "It has become obvious that consideration of only pathological anatomy gives little insight into the pathogenesis of cystic kidney disease. Better markers are required before an adequate system of classification can be developed. Once nosologic separation has been effected, specific diseases can be studied in more detail and an attempt can be made to elucidate the fundamental molecular abnormality. Genetic factors may be extremely useful in defining discrete disease entities; unfortunately, they have been too frequently disregarded by workers in the field. If progress is to be made in the area of structural abnormalities of the kidney, the common efforts of nephrologists, pathologists, physiologists, and geneticists will be required.", "contents": "Genetics in cystic kidney disease. It has become obvious that consideration of only pathological anatomy gives little insight into the pathogenesis of cystic kidney disease. Better markers are required before an adequate system of classification can be developed. Once nosologic separation has been effected, specific diseases can be studied in more detail and an attempt can be made to elucidate the fundamental molecular abnormality. Genetic factors may be extremely useful in defining discrete disease entities; unfortunately, they have been too frequently disregarded by workers in the field. If progress is to be made in the area of structural abnormalities of the kidney, the common efforts of nephrologists, pathologists, physiologists, and geneticists will be required."} {"id": "PMID:1264571", "title": "Renal cystic disease: radiologic appearance.", "content": "The great diversity of the various forms of renal cystic disease results in a formidable diagnostic challenge to the roentgenologist and clinician alike. Until recently, adequate diagnosis required surgical exploration or biopsy, or both, to establish benignity or to confirm the suspicion of a more esoteric form of renal cystic disease. Now, however, with refinements in excretory urography with tomography, bolus and infusion nephrotomography, selective renal arteriography, percutaneous aspiration of cysts, and sonography, the accuracy of a clinical diagnosis of cystic disease has approached that of surgical exploration and biopsy. In addition these noninvasive techniques eliminate the morbidity and mortality associated with surgical procedures.", "contents": "Renal cystic disease: radiologic appearance. The great diversity of the various forms of renal cystic disease results in a formidable diagnostic challenge to the roentgenologist and clinician alike. Until recently, adequate diagnosis required surgical exploration or biopsy, or both, to establish benignity or to confirm the suspicion of a more esoteric form of renal cystic disease. Now, however, with refinements in excretory urography with tomography, bolus and infusion nephrotomography, selective renal arteriography, percutaneous aspiration of cysts, and sonography, the accuracy of a clinical diagnosis of cystic disease has approached that of surgical exploration and biopsy. In addition these noninvasive techniques eliminate the morbidity and mortality associated with surgical procedures."} {"id": "PMID:1264572", "title": "Residues of organochlorines and heavy metals in ruddy ducks from the Delaware River, 1973.", "content": "In December 1973, eight ruddy ducks killed in an oil spill on the Delaware River were collected to be analyzed for residues of environmental pollutants. Whole carcasses were analyzed for organochlorine pesticides and livers were examined for lead, cadmium, and mercury. Residues of polychlorinated biphenyls and DDT and/or its metabolites were present in all carcasses. Dieldrin and hexachlorobenzene were present in seven of the eight samples. All livers contained detectable levels of lead, cadmium, and mercury.", "contents": "Residues of organochlorines and heavy metals in ruddy ducks from the Delaware River, 1973. In December 1973, eight ruddy ducks killed in an oil spill on the Delaware River were collected to be analyzed for residues of environmental pollutants. Whole carcasses were analyzed for organochlorine pesticides and livers were examined for lead, cadmium, and mercury. Residues of polychlorinated biphenyls and DDT and/or its metabolites were present in all carcasses. Dieldrin and hexachlorobenzene were present in seven of the eight samples. All livers contained detectable levels of lead, cadmium, and mercury."} {"id": "PMID:1264573", "title": "Chlorinated hydrocarbon pesticides and mercury in coastal young-of-the-year finfish, South Carolina and Georgia--1972-74.", "content": "Pesticides and heavy metals were monitored in fish collected from 11 estuaries representing all the Atlantic drainage basins in Georgia and South Carolina. Part of the U.S. Environmental Protection Agency National Estuarine Monitoring Program, the semianual survey of young-of-the-year fishes, was conducted from 1972 to 1974. Data are intended to provide an initial base line for residue levels in the fish studied in these waters. Dieldrin was found in 2 percent of the samples, DDT and metabolites were in 33 percent, polychlorinated biphenyls were in 4 percent, and mercury was in 47 percent. Noticeably absent were any measurable residues of toxaphene even though there is a toxaphene manufacturing plant in Brunswick, Ga.", "contents": "Chlorinated hydrocarbon pesticides and mercury in coastal young-of-the-year finfish, South Carolina and Georgia--1972-74. Pesticides and heavy metals were monitored in fish collected from 11 estuaries representing all the Atlantic drainage basins in Georgia and South Carolina. Part of the U.S. Environmental Protection Agency National Estuarine Monitoring Program, the semianual survey of young-of-the-year fishes, was conducted from 1972 to 1974. Data are intended to provide an initial base line for residue levels in the fish studied in these waters. Dieldrin was found in 2 percent of the samples, DDT and metabolites were in 33 percent, polychlorinated biphenyls were in 4 percent, and mercury was in 47 percent. Noticeably absent were any measurable residues of toxaphene even though there is a toxaphene manufacturing plant in Brunswick, Ga."} {"id": "PMID:1264574", "title": "Nationwide residues of organochlorines in wings of adult mallards and black ducks, 1972-73.", "content": "Organochlorine residues in wings of adult mallards and black ducks were monitored during the 1972-73 hunting season. DDE, DDT, DDD, dieldrin, and polychlorinated biphenyls (PCB's) were present in all samples. Mallard wings from Alabama contained the highest mean levels of DDE, DDT, DDD, dieldrin, and PCB's. Mallards and black ducks from the Atlantic Flyway and mallards from the Pacific Flyway contained significantly lower DDE residues than in 1969-70. Black ducks from the Atlantic Flyway contained significantly less dieldrin than in 1969-70, and mallards in the Central and Pacific Flyways contained significantly lower levels of PCB's. As in 1969-70, DDE residues were lowest in the Central Flyway and highest in the Atlantic Flyway. The average PCB level remained unchanged in the Atlantic Flyway but was higher in the Mississippi Flyway than in 1969-70, probably because of the unusually high levels in Alabama samples. All organochlorine residues in black ducks from the Atlantic Flyway significantly correlated. DDE concentrations in mallards from the Atlantic Flyway significantly correlated with those of DDT, DDD, and PCB's.", "contents": "Nationwide residues of organochlorines in wings of adult mallards and black ducks, 1972-73. Organochlorine residues in wings of adult mallards and black ducks were monitored during the 1972-73 hunting season. DDE, DDT, DDD, dieldrin, and polychlorinated biphenyls (PCB's) were present in all samples. Mallard wings from Alabama contained the highest mean levels of DDE, DDT, DDD, dieldrin, and PCB's. Mallards and black ducks from the Atlantic Flyway and mallards from the Pacific Flyway contained significantly lower DDE residues than in 1969-70. Black ducks from the Atlantic Flyway contained significantly less dieldrin than in 1969-70, and mallards in the Central and Pacific Flyways contained significantly lower levels of PCB's. As in 1969-70, DDE residues were lowest in the Central Flyway and highest in the Atlantic Flyway. The average PCB level remained unchanged in the Atlantic Flyway but was higher in the Mississippi Flyway than in 1969-70, probably because of the unusually high levels in Alabama samples. All organochlorine residues in black ducks from the Atlantic Flyway significantly correlated. DDE concentrations in mallards from the Atlantic Flyway significantly correlated with those of DDT, DDD, and PCB's."} {"id": "PMID:1264575", "title": "Seasonal concentrations of dieldrin in water, channel catfish, and catfish-food organisms, Des Moines River, Iowa--1971-73.", "content": "Concentrations of dieldrin in aquatic insects, crayfish, minnows, and small carpsuckers, and muscle tissue of channel catfish (Ictalurus punctatus) were compared with the dieldrin content of Des Moines River water in 1971-73. Monthly mean concentrations of dieldrin in river water and most aquatic organisms were highest in June and July, soon after aldrin had been applied to corn land in the watershed. Several groups of aquatic organisms also exhibited high dieldrin levels in the fall when the dieldrin content of river water was seasonally low. The influence of temperature on metabolic rate and enzyme activity and the differences in body fat content were suggested as probable causes of variations observed in the dieldrin content of aquatic organisms.", "contents": "Seasonal concentrations of dieldrin in water, channel catfish, and catfish-food organisms, Des Moines River, Iowa--1971-73. Concentrations of dieldrin in aquatic insects, crayfish, minnows, and small carpsuckers, and muscle tissue of channel catfish (Ictalurus punctatus) were compared with the dieldrin content of Des Moines River water in 1971-73. Monthly mean concentrations of dieldrin in river water and most aquatic organisms were highest in June and July, soon after aldrin had been applied to corn land in the watershed. Several groups of aquatic organisms also exhibited high dieldrin levels in the fall when the dieldrin content of river water was seasonally low. The influence of temperature on metabolic rate and enzyme activity and the differences in body fat content were suggested as probable causes of variations observed in the dieldrin content of aquatic organisms."} {"id": "PMID:1264589", "title": "[Gougerot-Sj\u00f6gren syndrome in patients with sarcoidosis].", "content": "Three patients with eye and salivary dryness presenting the scintigraphic and histological features of Sjogren's syndrome and also suffering from sarco\u00efdosis, are reported. The authors stress the rarity of clinically indentifiable dry oculo-salivary syndromes whilst routine scintigraphy of the principle salivary glands using technetium 99 m often reveals altered salivary function. They consider that the primary feature in the development of this dry salivary syndrome consists of fibro-inflammatory lesions of the glandular interstitium, seen in specimens of the glands of the labial mucosae, which are sequelae of the initial sarcoid infiltration. They point out that Sjogren's syndrome occurring in relation with sarco\u00efdosis has certain special features. These include its appearance in relatively young subjects, the minimal symptoms, the non-essential presence of inflammatory signs and the absence of associated connective tissue disorder.", "contents": "[Gougerot-Sj\u00f6gren syndrome in patients with sarcoidosis]. Three patients with eye and salivary dryness presenting the scintigraphic and histological features of Sjogren's syndrome and also suffering from sarco\u00efdosis, are reported. The authors stress the rarity of clinically indentifiable dry oculo-salivary syndromes whilst routine scintigraphy of the principle salivary glands using technetium 99 m often reveals altered salivary function. They consider that the primary feature in the development of this dry salivary syndrome consists of fibro-inflammatory lesions of the glandular interstitium, seen in specimens of the glands of the labial mucosae, which are sequelae of the initial sarcoid infiltration. They point out that Sjogren's syndrome occurring in relation with sarco\u00efdosis has certain special features. These include its appearance in relatively young subjects, the minimal symptoms, the non-essential presence of inflammatory signs and the absence of associated connective tissue disorder."} {"id": "PMID:1264599", "title": "[Diagnostic value of closed thorax pericardial biopsy. 20 cases].", "content": "Twenty patients with sub-acute and chronic pericarditis under went closed thorax pericardial biopsy. In three cases the examination brought to light a diagnosis of tuberculosis and in one of a tumoural origin. In 16 cases in which the aetiology was that of a non-specific pericarditis, the value of this examination, integrated into the context, is discussed.", "contents": "[Diagnostic value of closed thorax pericardial biopsy. 20 cases]. Twenty patients with sub-acute and chronic pericarditis under went closed thorax pericardial biopsy. In three cases the examination brought to light a diagnosis of tuberculosis and in one of a tumoural origin. In 16 cases in which the aetiology was that of a non-specific pericarditis, the value of this examination, integrated into the context, is discussed."} {"id": "PMID:1264608", "title": "[Stimulation of testicular secretion by chorionic gonadotrophin. Results in normal men and in hypogonadic patients].", "content": "In normal adult male, the intra-muscular hCG-test (5000 I.U. X 3) results in a progressive rise of plasma testosterone and dihydrotestosterone, and in a sharp increase of plasma estradiol followed by a decrease although th hCG stimulation is maintained. In testicular dysgenesis, the testosterone and estradiol responses are variable. In adult male gonadotropin deficiency, basal testosterone is always very low, and rises strongly, under hCG-test, only when previous and recent (less than 10 years) exposure to endogenous or exogenous gonadotropin had induced virilization ; by contrast the defective response of estradiol in all cases provides a reliable estimate of the actual gonadotropin deficiency.", "contents": "[Stimulation of testicular secretion by chorionic gonadotrophin. Results in normal men and in hypogonadic patients]. In normal adult male, the intra-muscular hCG-test (5000 I.U. X 3) results in a progressive rise of plasma testosterone and dihydrotestosterone, and in a sharp increase of plasma estradiol followed by a decrease although th hCG stimulation is maintained. In testicular dysgenesis, the testosterone and estradiol responses are variable. In adult male gonadotropin deficiency, basal testosterone is always very low, and rises strongly, under hCG-test, only when previous and recent (less than 10 years) exposure to endogenous or exogenous gonadotropin had induced virilization ; by contrast the defective response of estradiol in all cases provides a reliable estimate of the actual gonadotropin deficiency."} {"id": "PMID:1264609", "title": "[Type IIb primary hyperlipoproteinemia. An homogenous series of 412 cases].", "content": "On the basis of a homogeneous series of 412 cases of type IIb primary hyperlipoproteinaemia, the authors compare their experience with findings in the literature. The prevalence of this type of hyperlipoproteinaemia in the general population has been underestimated at 3%. Biological diagnosis remains simple (identification of a double and distinct excess in beta and pre beta lipoproteins). Extravascular lipid deposits (gerontoxon, xanthelasma, tendon xanthomata) are not type specific. Hyperlipidaemic syndrome is rare. Above all, the importance of type IIb in atheromatous disease in the young subject now seems obvious. The mode of hereditary transmission of the familial anomaly is not certain but would appear to be often associated with a double heterozygote condition.", "contents": "[Type IIb primary hyperlipoproteinemia. An homogenous series of 412 cases]. On the basis of a homogeneous series of 412 cases of type IIb primary hyperlipoproteinaemia, the authors compare their experience with findings in the literature. The prevalence of this type of hyperlipoproteinaemia in the general population has been underestimated at 3%. Biological diagnosis remains simple (identification of a double and distinct excess in beta and pre beta lipoproteins). Extravascular lipid deposits (gerontoxon, xanthelasma, tendon xanthomata) are not type specific. Hyperlipidaemic syndrome is rare. Above all, the importance of type IIb in atheromatous disease in the young subject now seems obvious. The mode of hereditary transmission of the familial anomaly is not certain but would appear to be often associated with a double heterozygote condition."} {"id": "PMID:1264610", "title": "[The exercise electrocardiogram after the acute phase of myocardial infection. Analysis of 100 cases].", "content": "A study was made of the effort electrocardiogram (ECG) of 100 patients who had had a myocardial infarction and correlated in 46 cases with findings at coronography. Angina occurred in 38 cases. The ECG remained stable in 17 cases and showed changes in 83. In 60 patients, in those leads with pathological Q waves, isolated T wave changes (15 cases), ST elevation (43 cases) or ST depression were seen. In 17 cases there was isolated ST depression in leads free of any signs of infarction. In 6 cases alterations in rhythm or conduction were seen.", "contents": "[The exercise electrocardiogram after the acute phase of myocardial infection. Analysis of 100 cases]. A study was made of the effort electrocardiogram (ECG) of 100 patients who had had a myocardial infarction and correlated in 46 cases with findings at coronography. Angina occurred in 38 cases. The ECG remained stable in 17 cases and showed changes in 83. In 60 patients, in those leads with pathological Q waves, isolated T wave changes (15 cases), ST elevation (43 cases) or ST depression were seen. In 17 cases there was isolated ST depression in leads free of any signs of infarction. In 6 cases alterations in rhythm or conduction were seen."} {"id": "PMID:1264611", "title": "[Renal insufficiency and diabetes cured by removal of a villous tumor of the rectum].", "content": "A case of villous tumour of the rectum presenting in a misleading fashion : clinically, an apparent adrenal insufficiency and biologically renal insufficiency and diabetes. The abnormal glucose metabolism was attributed to potassium deficiency. The conditions and frequency of occurence of hydroelectrolytic problems in association with villous tumours and the various presenting features, some misleading, are discussed. The difficulties of diagnosis and treatment are emphasised.", "contents": "[Renal insufficiency and diabetes cured by removal of a villous tumor of the rectum]. A case of villous tumour of the rectum presenting in a misleading fashion : clinically, an apparent adrenal insufficiency and biologically renal insufficiency and diabetes. The abnormal glucose metabolism was attributed to potassium deficiency. The conditions and frequency of occurence of hydroelectrolytic problems in association with villous tumours and the various presenting features, some misleading, are discussed. The difficulties of diagnosis and treatment are emphasised."} {"id": "PMID:1264625", "title": "[Changes in anti-tetanus antibodies under sero-toxoid therapy. Study in 50 patients with tetanus].", "content": "A study concerning changes in anti-tetanus antibody (ATA) levels in 50 patients with tetanus following the injection of antitetanic serum of equine origin and of toxoid, the first dose of the latter being given 24 hours after the administration of serum and the others at intervals of 5 to 7, 15 and 30 days. Repeated estimation of ATA demonstrated, regardless of the toxoid dose protocol adopted, that levels did not reach 0.1 IU/ml on the 30th day and that they only rose late. By contrast, after a booster, the increase was the same as that seen in subjects who had not acquired tetanus. The various factors which may underly defective active immunisation during the acute phase of tetanus are discussed. Heterologue serum therapy, which has been held responsible, cannot be considered to be a responsible factor since patients who did not receive serum behaved in exactly the same way as those who had. By virtue of this \"gap\" in the acquisition of immunity, the use of heterologue serum is recommended to neutralise any remaining circulating toxin as rapidly as possible.", "contents": "[Changes in anti-tetanus antibodies under sero-toxoid therapy. Study in 50 patients with tetanus]. A study concerning changes in anti-tetanus antibody (ATA) levels in 50 patients with tetanus following the injection of antitetanic serum of equine origin and of toxoid, the first dose of the latter being given 24 hours after the administration of serum and the others at intervals of 5 to 7, 15 and 30 days. Repeated estimation of ATA demonstrated, regardless of the toxoid dose protocol adopted, that levels did not reach 0.1 IU/ml on the 30th day and that they only rose late. By contrast, after a booster, the increase was the same as that seen in subjects who had not acquired tetanus. The various factors which may underly defective active immunisation during the acute phase of tetanus are discussed. Heterologue serum therapy, which has been held responsible, cannot be considered to be a responsible factor since patients who did not receive serum behaved in exactly the same way as those who had. By virtue of this \"gap\" in the acquisition of immunity, the use of heterologue serum is recommended to neutralise any remaining circulating toxin as rapidly as possible."} {"id": "PMID:1264636", "title": "[Descriptive anatomical study of the major coronary trunks and the principal epicardial collaterals. 125 cases].", "content": "Abnormalities at the origin are rare and involve only the left coronary artery: absence of the trunk of this artery in 3 cases, as a result of separation of the origins of the anterior interventricular and the left circumflex. As far as course is concerned, the principal abnormality involves the anterior interventricular: presence in 17% of cases of an intraparietal segment, quite narrow and with a thin wall which is remarkably fixed and constant in its different characteristics: rapid reading of a film taken during selective injection may lead to a conclusion of stenosis or to that of a non-existent spasm. In 6% of cases, the posterior interventricular is short, joined to the middle part of the posterior interventricular sulcus by a collateral of the right coronary. Thus in the case of a long stenosis of the right coronary artery, right aorto-coronary by-pass, distal, provides no blood supply to the postero-inferior part of the septum and the posterior part of the apex. In more than one third of cases the left first diagonal and marginal arteries are of sufficient calibre to permit implantation of an aorto-coronary graft.", "contents": "[Descriptive anatomical study of the major coronary trunks and the principal epicardial collaterals. 125 cases]. Abnormalities at the origin are rare and involve only the left coronary artery: absence of the trunk of this artery in 3 cases, as a result of separation of the origins of the anterior interventricular and the left circumflex. As far as course is concerned, the principal abnormality involves the anterior interventricular: presence in 17% of cases of an intraparietal segment, quite narrow and with a thin wall which is remarkably fixed and constant in its different characteristics: rapid reading of a film taken during selective injection may lead to a conclusion of stenosis or to that of a non-existent spasm. In 6% of cases, the posterior interventricular is short, joined to the middle part of the posterior interventricular sulcus by a collateral of the right coronary. Thus in the case of a long stenosis of the right coronary artery, right aorto-coronary by-pass, distal, provides no blood supply to the postero-inferior part of the septum and the posterior part of the apex. In more than one third of cases the left first diagonal and marginal arteries are of sufficient calibre to permit implantation of an aorto-coronary graft."} {"id": "PMID:1264653", "title": "[XXYY chromosomal constitution recognised during the 1st year of life].", "content": "The authors report two cases of infants with an XXYY chromosomal constitution. The anomaly was suspected in the presence of a particular facies associated with abnormalities of development of the external genitalia. The diagnosis was confirmed rapidly and easily by immunofluorescent study of buccal scrapings and polynu clear cells. Early diagnosis is a value with regard to family counselling.", "contents": "[XXYY chromosomal constitution recognised during the 1st year of life]. The authors report two cases of infants with an XXYY chromosomal constitution. The anomaly was suspected in the presence of a particular facies associated with abnormalities of development of the external genitalia. The diagnosis was confirmed rapidly and easily by immunofluorescent study of buccal scrapings and polynu clear cells. Early diagnosis is a value with regard to family counselling."} {"id": "PMID:1264654", "title": "[Rheumatoid polyarthritis: should corticotherapy be interrupted in case of gastro-duodenal ulcer?].", "content": "The possibility of healing of a corticosteroid-induced ulcer depsite the continuation of the treatment, is now an established fact. It is thus reasonable to continue corticosteroids in those cases where interupption severely compromises the prognosis. The chances of healing of the ulcer would appear to be great, especially when corticosteroids are being used in low dosage, but the exact frequency of healing remains unknown, just as the frequency of ulcers due to corticosteroid therapy has not been accurately established.", "contents": "[Rheumatoid polyarthritis: should corticotherapy be interrupted in case of gastro-duodenal ulcer?]. The possibility of healing of a corticosteroid-induced ulcer depsite the continuation of the treatment, is now an established fact. It is thus reasonable to continue corticosteroids in those cases where interupption severely compromises the prognosis. The chances of healing of the ulcer would appear to be great, especially when corticosteroids are being used in low dosage, but the exact frequency of healing remains unknown, just as the frequency of ulcers due to corticosteroid therapy has not been accurately established."} {"id": "PMID:1264664", "title": "[Poland's syndrome. Clinical and genetic studies; physiopathologic considerations].", "content": "Study of malformations of the hand makes possible the definition of three forms of progressive severity in the Poland syndrome, in which there is unilateral symbrachydactylie associated with homolateral aplasia of the pectoralis major. The three forms share the predominance of involvement of the 2nd, 3rd and 4th fingers. The existence of alterations in palmar creases and dermatoglyphia of the involved side alone confirms the absence of any lesion, even infra-clinical, of the other hand. Genetic study favours a pluri-factorial inheritance. Topographical data and the comparative study of vascularisation suggest the possibility of hypoplasia of the proximal portion of the sub-clavian at the origin of this malformative association.", "contents": "[Poland's syndrome. Clinical and genetic studies; physiopathologic considerations]. Study of malformations of the hand makes possible the definition of three forms of progressive severity in the Poland syndrome, in which there is unilateral symbrachydactylie associated with homolateral aplasia of the pectoralis major. The three forms share the predominance of involvement of the 2nd, 3rd and 4th fingers. The existence of alterations in palmar creases and dermatoglyphia of the involved side alone confirms the absence of any lesion, even infra-clinical, of the other hand. Genetic study favours a pluri-factorial inheritance. Topographical data and the comparative study of vascularisation suggest the possibility of hypoplasia of the proximal portion of the sub-clavian at the origin of this malformative association."} {"id": "PMID:1264665", "title": "[Fulminating streptococcal cellulitis. Importance of hypovolemic shock].", "content": "The authors report three cases. Hemostasis abnormalities and lowering of complement fractions was observed. Severe shock was lethal in two cases associated with severe local lesions. The role of unadapted treatment like corticosteroids and the lack of early penicillino therapy is discussed to explain this evolution.", "contents": "[Fulminating streptococcal cellulitis. Importance of hypovolemic shock]. The authors report three cases. Hemostasis abnormalities and lowering of complement fractions was observed. Severe shock was lethal in two cases associated with severe local lesions. The role of unadapted treatment like corticosteroids and the lack of early penicillino therapy is discussed to explain this evolution."} {"id": "PMID:1264668", "title": "[Bacterial adjuvants in cell mediated immunity. Recent data].", "content": "Only some bacterial adjuvants are able to stimulate cell-mediated immunity. It has been shown recently that this property is due to a cell-wall component, the peptidoglycan. The relevance of these findings to tumor immunity has been discussed.", "contents": "[Bacterial adjuvants in cell mediated immunity. Recent data]. Only some bacterial adjuvants are able to stimulate cell-mediated immunity. It has been shown recently that this property is due to a cell-wall component, the peptidoglycan. The relevance of these findings to tumor immunity has been discussed."} {"id": "PMID:1264682", "title": "[Should all prosthetic valve patients be treated by platelet inhibitors?].", "content": "The number, volume and adhesive and aggregation activities of platelets were studied in 31 patients with artificial valves. The differences observed in comparison with a control population are due to stimulation of thrombocytopoiesis secondary to the destruction or concumption of the platelets, it being impossible to be sure as to the dominant mechanism. Under these circumstances it would seem important in each patient to verify the therapeutic effectiveness of platelet inhibitors or of traditionnal anticoagulants by direct or indirect study of platelet life duration.", "contents": "[Should all prosthetic valve patients be treated by platelet inhibitors?]. The number, volume and adhesive and aggregation activities of platelets were studied in 31 patients with artificial valves. The differences observed in comparison with a control population are due to stimulation of thrombocytopoiesis secondary to the destruction or concumption of the platelets, it being impossible to be sure as to the dominant mechanism. Under these circumstances it would seem important in each patient to verify the therapeutic effectiveness of platelet inhibitors or of traditionnal anticoagulants by direct or indirect study of platelet life duration."} {"id": "PMID:1264699", "title": "[Irapa type spondylo-epiphyso-metaphyseal osteochondrodysplasia. New type of dwarfism with short spine and metatarsals].", "content": "A new dwarfism of a spondyloepiphysometaphyseal dysplasia is described among Venezuelan Indians of the Yukpa (Irapa) tribe. Brachyrrhahia, brachymetatarsia and brachyrhyzomelia in upper limbs and manifestations in proximal epiphyses of femora and distal epiphyses of humera, with moderate to serious impairment of gait, but no significance deviations of the spine, are the main clinical findings. It is a well individualized type among a very heterogeneous and ill-defined group of chondrodystrophies. The inheritance is through an autosomal recessive or less probably an X-linked gene.", "contents": "[Irapa type spondylo-epiphyso-metaphyseal osteochondrodysplasia. New type of dwarfism with short spine and metatarsals]. A new dwarfism of a spondyloepiphysometaphyseal dysplasia is described among Venezuelan Indians of the Yukpa (Irapa) tribe. Brachyrrhahia, brachymetatarsia and brachyrhyzomelia in upper limbs and manifestations in proximal epiphyses of femora and distal epiphyses of humera, with moderate to serious impairment of gait, but no significance deviations of the spine, are the main clinical findings. It is a well individualized type among a very heterogeneous and ill-defined group of chondrodystrophies. The inheritance is through an autosomal recessive or less probably an X-linked gene."} {"id": "PMID:1264700", "title": "[12 years of medical treatment of Cushing's disease. Long-term use of Op, DDD in 46 cases].", "content": "The authors report the results of the medical treatment in 46 cases of Cushing's disease. Long-term Op,DDD therapy apparently results in a drug-induced total adrenal suppression in 28 cases. In 12 cases it reduces the adrenal secretion down to the normal level. In only 6 cases of this series was the treatment unsuccessful. Accordingly the authors think that long-term medical treatment with Op,DDD deserves to be considered as a major total tool within the therapy of Cushing's disease. However regular and precise monitoring under therapy is necessary. The schema of the method used is described.", "contents": "[12 years of medical treatment of Cushing's disease. Long-term use of Op, DDD in 46 cases]. The authors report the results of the medical treatment in 46 cases of Cushing's disease. Long-term Op,DDD therapy apparently results in a drug-induced total adrenal suppression in 28 cases. In 12 cases it reduces the adrenal secretion down to the normal level. In only 6 cases of this series was the treatment unsuccessful. Accordingly the authors think that long-term medical treatment with Op,DDD deserves to be considered as a major total tool within the therapy of Cushing's disease. However regular and precise monitoring under therapy is necessary. The schema of the method used is described."} {"id": "PMID:1264701", "title": "[Acute purulent meningitis of traumatic origin. 16 cases].", "content": "The current frequency of road accidents leads to the necessity to seek a possible head injury in the past history of patients suffereing from acute purulent meningitis. This investigation must be all the more assiduous in the presence of a meningitis which is pneumococcal in origin and recurrent. Rhinorrhoea is a sign of primary importance. Tomography of the frontal and sagittal views of the skul remains of value. Radio-isotope studies of the CSF happile make up for the deficiencies of radiological examination, without providing an infallible means for the detection of osteomeningitis defects. The authors report their findings and therapeutic results in 16 patients collected in a series of 162 cases of acute purulent meningitis.", "contents": "[Acute purulent meningitis of traumatic origin. 16 cases]. The current frequency of road accidents leads to the necessity to seek a possible head injury in the past history of patients suffereing from acute purulent meningitis. This investigation must be all the more assiduous in the presence of a meningitis which is pneumococcal in origin and recurrent. Rhinorrhoea is a sign of primary importance. Tomography of the frontal and sagittal views of the skul remains of value. Radio-isotope studies of the CSF happile make up for the deficiencies of radiological examination, without providing an infallible means for the detection of osteomeningitis defects. The authors report their findings and therapeutic results in 16 patients collected in a series of 162 cases of acute purulent meningitis."} {"id": "PMID:1264702", "title": "[The role of pericardial pathology in internal medicine].", "content": "In the multiple pathology of a non-specialised patient group in internal medicine, 1,2% presented with a pericardial disorder. The true occurrence rate of pericarditis is in fact much higher since if the cases where pericarditis is found only at autopsy are taken into consideration, pericardial involvement is found in almost 10% (this figure is higher, for obvious aetiological reasons, than that for non-fatal peridarditis). The improvement in obtaining a positive diagnosis of pericarditis is obvious when a study carried out ten years ago is reviewed. Finally, comparison of the aetiological types in our study with those seen in cardiology services shows important differences and takes account of the special nature of pericardial pathology in general medicine and the interest of its study.", "contents": "[The role of pericardial pathology in internal medicine]. In the multiple pathology of a non-specialised patient group in internal medicine, 1,2% presented with a pericardial disorder. The true occurrence rate of pericarditis is in fact much higher since if the cases where pericarditis is found only at autopsy are taken into consideration, pericardial involvement is found in almost 10% (this figure is higher, for obvious aetiological reasons, than that for non-fatal peridarditis). The improvement in obtaining a positive diagnosis of pericarditis is obvious when a study carried out ten years ago is reviewed. Finally, comparison of the aetiological types in our study with those seen in cardiology services shows important differences and takes account of the special nature of pericardial pathology in general medicine and the interest of its study."} {"id": "PMID:1264703", "title": "[Serum antibodies in urinary infection in children. Significance and relation to pyelonephritis].", "content": "Serum antibodies were measured repeatedly in 176 cases of urinary tract infections in children. The method used, passive haemagglutination with the bacterial antigen of the patient's urinary infection, gives a positive reading from 1/160. Antibodies were found in 139 cases and the lower limit compatible with a diagnosis of pyelonephritis was 1/2560. The result may, however, be negative in infants of less than one year. As in the first publication, the authors describe three types of curves of progression. Analysis confirms the relationship between persistent antibodies and evolutive pyelonephritis. Experimental results and a comparison of clinical and pathological findings are discussed and support the notion of the value of a persistent high antibody level in the diagnosis of chronic pyelonephritis.", "contents": "[Serum antibodies in urinary infection in children. Significance and relation to pyelonephritis]. Serum antibodies were measured repeatedly in 176 cases of urinary tract infections in children. The method used, passive haemagglutination with the bacterial antigen of the patient's urinary infection, gives a positive reading from 1/160. Antibodies were found in 139 cases and the lower limit compatible with a diagnosis of pyelonephritis was 1/2560. The result may, however, be negative in infants of less than one year. As in the first publication, the authors describe three types of curves of progression. Analysis confirms the relationship between persistent antibodies and evolutive pyelonephritis. Experimental results and a comparison of clinical and pathological findings are discussed and support the notion of the value of a persistent high antibody level in the diagnosis of chronic pyelonephritis."} {"id": "PMID:1264713", "title": "[HL-A antigens in patients with psoriatic rheumatism].", "content": "The authors studied HLA tissue groups for 28 specificities in 70 patients with psoriatic arthropathy (44 with pure peripheral arthropathy and 26 with axial involvement, 19 of whom also had peripheral lesions). Four antigens of this system were found with a significantly increased frequency in 70 patients in comparison with a control group of 152 normal subjects. For antigen HLA-B27, the frequency seemed very significantly increased in patients with axial involvement as compared with those without axial troubles (pc less than or equal to 0.0001) and with the controls (pc less than or equal to 0.0001). For antigen HLA-B13, the frequency was significantly increased in patients with axial involvement as compared with the controls (pc less than 0.05). Antigen HLA-Bw17 was present with significantly increased frequency as compared with the controls in the patients with peripheral involvement (pc less than 0.001). For antigen HLA-Bw38 (W16.1), the frequency in patients with or without axial involvement was significantly increased in comparison with the controls (pc less than 0.001). The interpretation of these results is discussed and the association of antigen HLA-B27 with sacro-iliac involvement once again stressed.", "contents": "[HL-A antigens in patients with psoriatic rheumatism]. The authors studied HLA tissue groups for 28 specificities in 70 patients with psoriatic arthropathy (44 with pure peripheral arthropathy and 26 with axial involvement, 19 of whom also had peripheral lesions). Four antigens of this system were found with a significantly increased frequency in 70 patients in comparison with a control group of 152 normal subjects. For antigen HLA-B27, the frequency seemed very significantly increased in patients with axial involvement as compared with those without axial troubles (pc less than or equal to 0.0001) and with the controls (pc less than or equal to 0.0001). For antigen HLA-B13, the frequency was significantly increased in patients with axial involvement as compared with the controls (pc less than 0.05). Antigen HLA-Bw17 was present with significantly increased frequency as compared with the controls in the patients with peripheral involvement (pc less than 0.001). For antigen HLA-Bw38 (W16.1), the frequency in patients with or without axial involvement was significantly increased in comparison with the controls (pc less than 0.001). The interpretation of these results is discussed and the association of antigen HLA-B27 with sacro-iliac involvement once again stressed."} {"id": "PMID:1264714", "title": "[Ultrasonic echocardiography in the normal newborn infant. Application to the diagnosis of congenital cardiopathies].", "content": "Ultrasound echocardiography is automatic easy to carry out even in children in a precarious condition. The authors show the value of echocardiography in the neonatal period in a preliminary study involving 50 normal newborn infants. They discuss the cardiac abnormalities which may be diagnosed using this technique.", "contents": "[Ultrasonic echocardiography in the normal newborn infant. Application to the diagnosis of congenital cardiopathies]. Ultrasound echocardiography is automatic easy to carry out even in children in a precarious condition. The authors show the value of echocardiography in the neonatal period in a preliminary study involving 50 normal newborn infants. They discuss the cardiac abnormalities which may be diagnosed using this technique."} {"id": "PMID:1264721", "title": "[Degenerative spondylolisthesis. Clinical manifestations and treatment apropos of 26 operated cases].", "content": "The authors report 26 cases of surgically treated degenerative spondylolisthesis. Twelve patients complained of permanent uni or bilateral sciatica. All the others had a syndrome of intermittent claudication with pain and paresthaesia. The authors stress once again the highly evocative nature of this syndrome which reflects involvement of the nerve roots in the stenosed lumbar canal. Treatment consisted of lamino-arthrectomy which resulted in the disappearance of symptoms in most of cases. In four cases, vertebral slipping worsened during the post-operative cowise with, in three cases a recurrence of symptoms necessitating a complementary arthrodesis. This risk of increased slipping is a result of the instability created by the arthrectomy, especially when it is bilateral, and has led the authors to widen their indications for routine complementary postero-lateral arthrodesis.", "contents": "[Degenerative spondylolisthesis. Clinical manifestations and treatment apropos of 26 operated cases]. The authors report 26 cases of surgically treated degenerative spondylolisthesis. Twelve patients complained of permanent uni or bilateral sciatica. All the others had a syndrome of intermittent claudication with pain and paresthaesia. The authors stress once again the highly evocative nature of this syndrome which reflects involvement of the nerve roots in the stenosed lumbar canal. Treatment consisted of lamino-arthrectomy which resulted in the disappearance of symptoms in most of cases. In four cases, vertebral slipping worsened during the post-operative cowise with, in three cases a recurrence of symptoms necessitating a complementary arthrodesis. This risk of increased slipping is a result of the instability created by the arthrectomy, especially when it is bilateral, and has led the authors to widen their indications for routine complementary postero-lateral arthrodesis."} {"id": "PMID:1264853", "title": "The metabolic and structural changes of the liver in experimental animals after administration of isoprenaline.", "content": "Application to rats and rabbits of higher doses of isoprenaline (IP) results in derangement of glycid metabolism, manifested by the decrease of free glycogen (free-GL), and in an even more significant impairment of lipid metabolism, evidenced by an earlier increase of non-esterified fatty acids (NEFA) followed by an increase of esterified fatty acids (EFA) and a concomitant development of fatty infiltration, all indicators of marked lipomobilization. Histograms obtained from hypersensitive individuals show besides fatty infiltrations also necrobiotic processes and structural changes, seen as distinctly marked liver cell membranes. It is perhaps relevant to draw attention to the fact that there are both individual and species differences in the metabolic changes ensuing on application of IP.", "contents": "The metabolic and structural changes of the liver in experimental animals after administration of isoprenaline. Application to rats and rabbits of higher doses of isoprenaline (IP) results in derangement of glycid metabolism, manifested by the decrease of free glycogen (free-GL), and in an even more significant impairment of lipid metabolism, evidenced by an earlier increase of non-esterified fatty acids (NEFA) followed by an increase of esterified fatty acids (EFA) and a concomitant development of fatty infiltration, all indicators of marked lipomobilization. Histograms obtained from hypersensitive individuals show besides fatty infiltrations also necrobiotic processes and structural changes, seen as distinctly marked liver cell membranes. It is perhaps relevant to draw attention to the fact that there are both individual and species differences in the metabolic changes ensuing on application of IP."} {"id": "PMID:1264854", "title": "Pharmacobotanical investigations on some species of the Scrophulariaceae family. Part V. Chemical constitutents in Lathraea squamaria L.", "content": "From the Lathraea squamaria L. aucuboside and D-mannitol have been isolated and the presence of glucose, fructose and the ester of aucuboside stated. In the fraction after hydrolysis the presence of 6 phenolic acids has been found. The glucosides of the aucuboside group have been considered as elements of chemotaxonomical meaning.", "contents": "Pharmacobotanical investigations on some species of the Scrophulariaceae family. Part V. Chemical constitutents in Lathraea squamaria L. From the Lathraea squamaria L. aucuboside and D-mannitol have been isolated and the presence of glucose, fructose and the ester of aucuboside stated. In the fraction after hydrolysis the presence of 6 phenolic acids has been found. The glucosides of the aucuboside group have been considered as elements of chemotaxonomical meaning."} {"id": "PMID:1264855", "title": "Studies on the synergism of some hypotensive drugs with ethanol.", "content": "Synergism of some hypotensive drugs with ethanol was studied for its influence on the central nervous system. A very strong central action of the drugs and ethanol administered simultaneously in subthreshold doses was observed. Intensity of synergism was calculated by comparing the results with the effective doses of each drug administered seperately.", "contents": "Studies on the synergism of some hypotensive drugs with ethanol. Synergism of some hypotensive drugs with ethanol was studied for its influence on the central nervous system. A very strong central action of the drugs and ethanol administered simultaneously in subthreshold doses was observed. Intensity of synergism was calculated by comparing the results with the effective doses of each drug administered seperately."} {"id": "PMID:1264856", "title": "The influence of cholinomimetics on bioelectric activity of rabbit's limbic system and behaviour.", "content": "The influence of acetylcholine, physostigmine, and carbachole administered systemically in aqueous solutions and the volume of 2 or 3 mul to dorsal hippocampus (DH) or basal amygdaloid nucleus (BA) on rabbit's EEG and behaviour in chronic experiment was examined. EEGs were recorded from anterior cingular gyrus, DH, BA and medial hypothalamus. The excitation or attack activities after the administered compounds and of the receptors sensitive to acetylcholine in DH and BA were stated. Moreover, a strong functional connection of DH and BA was observed.", "contents": "The influence of cholinomimetics on bioelectric activity of rabbit's limbic system and behaviour. The influence of acetylcholine, physostigmine, and carbachole administered systemically in aqueous solutions and the volume of 2 or 3 mul to dorsal hippocampus (DH) or basal amygdaloid nucleus (BA) on rabbit's EEG and behaviour in chronic experiment was examined. EEGs were recorded from anterior cingular gyrus, DH, BA and medial hypothalamus. The excitation or attack activities after the administered compounds and of the receptors sensitive to acetylcholine in DH and BA were stated. Moreover, a strong functional connection of DH and BA was observed."} {"id": "PMID:1264857", "title": "On the choice of so-called placebo solution for the intranigral microinjection in the rat.", "content": "Rats moving freely in their cages were injected into substantia nigra with bidistilled water, with NaCl solutions of various concentrations or with a multionic Merle's solution. The solutions were administered uni- or bilaterally at volumes of 1-5 mul through chronically implanted chemitrodes. The behavior of animals and the EEG of frontal cortex, hippocampus, caudate nucleus and substantia nigra were observed. A part of the usual EEG record analysis two channels of EEG were evaluated with amplitude integrators. The main goal of the experiment was to find the optimal solvent for microinjection into the substantia nigra. So-called physiological saline solution (0-9% NaCl) was found to be most toxic and the multionic Merle's solution most suitable among the control fluids tested. The influence of \"pressing effect\", of pH as well as the influence of ionic concentrations of solutions tested are discussed.", "contents": "On the choice of so-called placebo solution for the intranigral microinjection in the rat. Rats moving freely in their cages were injected into substantia nigra with bidistilled water, with NaCl solutions of various concentrations or with a multionic Merle's solution. The solutions were administered uni- or bilaterally at volumes of 1-5 mul through chronically implanted chemitrodes. The behavior of animals and the EEG of frontal cortex, hippocampus, caudate nucleus and substantia nigra were observed. A part of the usual EEG record analysis two channels of EEG were evaluated with amplitude integrators. The main goal of the experiment was to find the optimal solvent for microinjection into the substantia nigra. So-called physiological saline solution (0-9% NaCl) was found to be most toxic and the multionic Merle's solution most suitable among the control fluids tested. The influence of \"pressing effect\", of pH as well as the influence of ionic concentrations of solutions tested are discussed."} {"id": "PMID:1264858", "title": "The effect of neuroleptics on the development of gastric ulcers in rats exposed to restraint-cold stress.", "content": "Gastric ulcer development and changes in the contents of glucose, free fatty acids (FFA), and K and Ca ions in the blood were studied in rats subjected to a graded stress of immobilisation and cold. During stress the volume of secretion and the output of HCl, decreased although the concentration rose slightly. Chlorpromazine (CPZ), thioridazine (TRZ), spiroperidol (SPI), and fluphenazine (FLU) inhibited to various degrees ulcer formation during stress. SPI reduced stress-induced mucosal damages in 94%, but FLU even in doses 100 times smaller than those of the other drugs counteracted ulcer formation. CPZ, TRZ and SPI in preventive doses increased proportionally the blood glucose level both in control rats and in those subject to stress. FLU in effective doses produced no hyperglycemia either in control rats or in those exposed to stress. We conclude that the prevention of gastric ulcer development by neuroleptics may be the result of their antisecretory action and counteracting of breakdown of sympathetic activity during severe stress.", "contents": "The effect of neuroleptics on the development of gastric ulcers in rats exposed to restraint-cold stress. Gastric ulcer development and changes in the contents of glucose, free fatty acids (FFA), and K and Ca ions in the blood were studied in rats subjected to a graded stress of immobilisation and cold. During stress the volume of secretion and the output of HCl, decreased although the concentration rose slightly. Chlorpromazine (CPZ), thioridazine (TRZ), spiroperidol (SPI), and fluphenazine (FLU) inhibited to various degrees ulcer formation during stress. SPI reduced stress-induced mucosal damages in 94%, but FLU even in doses 100 times smaller than those of the other drugs counteracted ulcer formation. CPZ, TRZ and SPI in preventive doses increased proportionally the blood glucose level both in control rats and in those subject to stress. FLU in effective doses produced no hyperglycemia either in control rats or in those exposed to stress. We conclude that the prevention of gastric ulcer development by neuroleptics may be the result of their antisecretory action and counteracting of breakdown of sympathetic activity during severe stress."} {"id": "PMID:1264859", "title": "Synthesis of 2,4-disubstituted 5-aminopyrimidine-6-carboxylic acids derivatives part I.", "content": "5-Benzoyloaminoorotic acid in a reaction with POCl3 forms 2,4-dichloro-5-benzylo-aminopyrimidine-6-carboxylic acid lactam 3, which heated with aliphatic and aromatic amines gives corresponding amides 6-11. These compounds don't show any antiinflammatory or antivirus activity.", "contents": "Synthesis of 2,4-disubstituted 5-aminopyrimidine-6-carboxylic acids derivatives part I. 5-Benzoyloaminoorotic acid in a reaction with POCl3 forms 2,4-dichloro-5-benzylo-aminopyrimidine-6-carboxylic acid lactam 3, which heated with aliphatic and aromatic amines gives corresponding amides 6-11. These compounds don't show any antiinflammatory or antivirus activity."} {"id": "PMID:1264860", "title": "Kinetics of drug decomposition. Part 37. Kinetics of autoxidation of narcotine in aqueous solutions.", "content": "The overall apparent first-order rate constants for the reaction of autoxidation of Narcotine (NC) - k1 and Cotarnine (CT) - k2 and the rate constants for autoxidation of the protonated (ks) and undissociated (kb) forms have been determined. The kinetic equation for the reaction of autoxidation at constant concentration of NC, CT and the atmospheric oxygen depending on the pH of the reaction medium has been established as: k1 = ks([H+]/([H+]+K'a))+kb(K'a/([H+]+K'a), k2=(ks[H+]+K'a))+kb (K'a/([H+]+K'a) (1+1+1/kt+1K)). The following thermodynamic parameters for the rate constants ks and kb have been calculated: deltaH not equal to, log A and deltaS not equal to.", "contents": "Kinetics of drug decomposition. Part 37. Kinetics of autoxidation of narcotine in aqueous solutions. The overall apparent first-order rate constants for the reaction of autoxidation of Narcotine (NC) - k1 and Cotarnine (CT) - k2 and the rate constants for autoxidation of the protonated (ks) and undissociated (kb) forms have been determined. The kinetic equation for the reaction of autoxidation at constant concentration of NC, CT and the atmospheric oxygen depending on the pH of the reaction medium has been established as: k1 = ks([H+]/([H+]+K'a))+kb(K'a/([H+]+K'a), k2=(ks[H+]+K'a))+kb (K'a/([H+]+K'a) (1+1+1/kt+1K)). The following thermodynamic parameters for the rate constants ks and kb have been calculated: deltaH not equal to, log A and deltaS not equal to."} {"id": "PMID:1264861", "title": "Derivatives of the L-lysine-peptides with antibacterial activity.", "content": "A number of derivatives of the L-lysine peptides has been obtained and their antibacterial properties were evaluated and compared with those of the ethyl ester of Nalpha-palmitoyl-L-lysyl-L-lysine dihydrochloride. Some correlations have been found between the chemical structure and antibacterial activity of the compounds.", "contents": "Derivatives of the L-lysine-peptides with antibacterial activity. A number of derivatives of the L-lysine peptides has been obtained and their antibacterial properties were evaluated and compared with those of the ethyl ester of Nalpha-palmitoyl-L-lysyl-L-lysine dihydrochloride. Some correlations have been found between the chemical structure and antibacterial activity of the compounds."} {"id": "PMID:1264862", "title": "The search for new drugs in the group of xanthine derivatives. Part XL. 7-Aminoxyalkyltheophyllines.", "content": "7-Aminoxyalkyltheophyllines 4-6 were obtained in good yield by acidolysis or hydrazinolysis of 7-phtalimidoxyalkyltheophyllines 1-3. The structure of obtained compounds was confirmed on chemical routs by preparing typical derivatives (acyl, and oximes) and by UV, IR and NMR spectra.", "contents": "The search for new drugs in the group of xanthine derivatives. Part XL. 7-Aminoxyalkyltheophyllines. 7-Aminoxyalkyltheophyllines 4-6 were obtained in good yield by acidolysis or hydrazinolysis of 7-phtalimidoxyalkyltheophyllines 1-3. The structure of obtained compounds was confirmed on chemical routs by preparing typical derivatives (acyl, and oximes) and by UV, IR and NMR spectra."} {"id": "PMID:1264882", "title": "Transient ischemic attacks: Pathophysiology and medical management.", "content": "There is substantial evidence to support the concept that most transient ischemic attacks (TIAs) are caused by microemboli that originate in areas of atherosclerosis in the blood vessels of the neck. TIA's are important risk factors in the development of stroke. The most common clinical features of TIAs caused by carotid insufficiency are hemianesthesia and hemiparesis; other symptoms in these cases include headache, dysphasia, and visual field distrubance. By far the most common clinical manifestation of vertebrobasilar insufficiency is vertigo.", "contents": "Transient ischemic attacks: Pathophysiology and medical management. There is substantial evidence to support the concept that most transient ischemic attacks (TIAs) are caused by microemboli that originate in areas of atherosclerosis in the blood vessels of the neck. TIA's are important risk factors in the development of stroke. The most common clinical features of TIAs caused by carotid insufficiency are hemianesthesia and hemiparesis; other symptoms in these cases include headache, dysphasia, and visual field distrubance. By far the most common clinical manifestation of vertebrobasilar insufficiency is vertigo."} {"id": "PMID:1264883", "title": "Radiologic examination of patients with stroke.", "content": "The reasons for radiologic evaluation of patients with cerebrovascular accidents, or strokes, and transient ischemic attacks are (1) to demonstrate surgically correctable vascular lesions and intracerebral masses due to hematomas and (2) when necessary, to confirm a diagnosis of atherosclerotic brain disease and rule out the presence of such conditions as subdural hematoma, aneurysm, arteriovenous malformation, or tumor. The radiologic techniques available include plain skull radiography, ultrasound, radionuclide scanning, computerized transaxial tomography (CTT), and cerebral angiography.", "contents": "Radiologic examination of patients with stroke. The reasons for radiologic evaluation of patients with cerebrovascular accidents, or strokes, and transient ischemic attacks are (1) to demonstrate surgically correctable vascular lesions and intracerebral masses due to hematomas and (2) when necessary, to confirm a diagnosis of atherosclerotic brain disease and rule out the presence of such conditions as subdural hematoma, aneurysm, arteriovenous malformation, or tumor. The radiologic techniques available include plain skull radiography, ultrasound, radionuclide scanning, computerized transaxial tomography (CTT), and cerebral angiography."} {"id": "PMID:1264884", "title": "The role of surgery in ischemic stroke.", "content": "Surgery in the management of stroke is useful primarily as a stroke-preventive measure for patients with extracranial carotid artery occlusive disease. Ideally, lesions that are potential sources of ischemia are removed before a fixed neurologic deficit can occur. Patients with transient ischemic attacks and no deficit or only minor neurologic deficit comprise the largest group of surgical candidates. Diagnostic angiography must be carried out before endarterectomy and should include aortic arch studies of both extracranial and intracranial carotid arteries. Placement of an intra-arterial catheter at the beginning of surgery provides the best method of monitoring arterial pressure. A postoperative angiogram allows visual confirmation of the patency of reconstructed vessels. Such confirmation is particularly important if patients have severely stenotic bilateral carotid artery disease. The surgical mortality for all patients with TIAs is between 1% and 2% in those clinics in which this type of operation is commonly done.", "contents": "The role of surgery in ischemic stroke. Surgery in the management of stroke is useful primarily as a stroke-preventive measure for patients with extracranial carotid artery occlusive disease. Ideally, lesions that are potential sources of ischemia are removed before a fixed neurologic deficit can occur. Patients with transient ischemic attacks and no deficit or only minor neurologic deficit comprise the largest group of surgical candidates. Diagnostic angiography must be carried out before endarterectomy and should include aortic arch studies of both extracranial and intracranial carotid arteries. Placement of an intra-arterial catheter at the beginning of surgery provides the best method of monitoring arterial pressure. A postoperative angiogram allows visual confirmation of the patency of reconstructed vessels. Such confirmation is particularly important if patients have severely stenotic bilateral carotid artery disease. The surgical mortality for all patients with TIAs is between 1% and 2% in those clinics in which this type of operation is commonly done."} {"id": "PMID:1264885", "title": "Rehabilitating patients with stroke.", "content": "Experience at the Burke Rehabilitation Center indicates that a rehabilitation program established early and giving proper attention to both personal and medical aspects can make it possible for 80% of stroke victims to return home and to function with reasonable adequacy. Rehabilitation efforts should begin as soon as possible after a stroke and can be effectively carried out in community hospitals.", "contents": "Rehabilitating patients with stroke. Experience at the Burke Rehabilitation Center indicates that a rehabilitation program established early and giving proper attention to both personal and medical aspects can make it possible for 80% of stroke victims to return home and to function with reasonable adequacy. Rehabilitation efforts should begin as soon as possible after a stroke and can be effectively carried out in community hospitals."} {"id": "PMID:1264886", "title": "Traumatic injuries: office treatment of minor burns.", "content": "While minor burns are not life threatening, they may result in significant morbidity, such as loss of function, prolonged healing time, and scarring. Proper office care is mandatory if such complications are to be prevented.", "contents": "Traumatic injuries: office treatment of minor burns. While minor burns are not life threatening, they may result in significant morbidity, such as loss of function, prolonged healing time, and scarring. Proper office care is mandatory if such complications are to be prevented."} {"id": "PMID:1264887", "title": "Community medicine: screening for rubella on a university campus.", "content": "Today's college-age students have not benefited from the mass immunization of children that followed the introduction of live attenuated rubella vaccine in 1969. Speculation on one university campus as to the number of young women who were susceptible to rubella led to a pilot program of rubella screening and a follow-up program of immunization and provided valuable data on the need for such a project.", "contents": "Community medicine: screening for rubella on a university campus. Today's college-age students have not benefited from the mass immunization of children that followed the introduction of live attenuated rubella vaccine in 1969. Speculation on one university campus as to the number of young women who were susceptible to rubella led to a pilot program of rubella screening and a follow-up program of immunization and provided valuable data on the need for such a project."} {"id": "PMID:1264893", "title": "Dealing with possible rabies exposure.", "content": "When a patient has come in contact with a domestic or wild animal that may be rabid, the physician must decide whether postexposure rabies prophylaxis is warranted. Among the factors that must be weighed are the animal species involved, the epizootiology of rabies, and the circumstances surrounding the exposure.", "contents": "Dealing with possible rabies exposure. When a patient has come in contact with a domestic or wild animal that may be rabid, the physician must decide whether postexposure rabies prophylaxis is warranted. Among the factors that must be weighed are the animal species involved, the epizootiology of rabies, and the circumstances surrounding the exposure."} {"id": "PMID:1264894", "title": "Selecting chemotherapy for metastatic breast cancer.", "content": "When cytotoxic chemotherapy is indicated in metastatic breast cancer, usually a combination of an alkylating agent and an antimetabolite, with or without doxorubicin, is used. The combinations including doxorubicin appear to give the best response rate.", "contents": "Selecting chemotherapy for metastatic breast cancer. When cytotoxic chemotherapy is indicated in metastatic breast cancer, usually a combination of an alkylating agent and an antimetabolite, with or without doxorubicin, is used. The combinations including doxorubicin appear to give the best response rate."} {"id": "PMID:1264895", "title": "Diuretic agents. Mechanisms of action and clinical uses.", "content": "Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. Furosemide (Lasix), ethacrynic acid (Edecrin), and possibly organomercurial agents are effective in the ascending limb of Henle's loop. Thiazides are the major agents acting in the early distal tubule. In the late distal tubule and collecting duct, spironolactone (Aldactone) and triamterene (Dyrenium) are useful, especially in combination with diuretics which act more proximally. In treating edematous states, initial therapy with thiazides is effective in most patients who do not exhibit moderate or severe renal insufficiency, severe hyperaldosteronism with excessive distal reabsorption of sodium in exchange for potassium, or excessive sodium reabsorption in the proximal tubule or ascending limb. Nonedematous states in which diuretic therapy is useful include hypertension, hypercalcemia, hypercalciuria, diabetes insipidus, and acute renal failure.", "contents": "Diuretic agents. Mechanisms of action and clinical uses. Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. Furosemide (Lasix), ethacrynic acid (Edecrin), and possibly organomercurial agents are effective in the ascending limb of Henle's loop. Thiazides are the major agents acting in the early distal tubule. In the late distal tubule and collecting duct, spironolactone (Aldactone) and triamterene (Dyrenium) are useful, especially in combination with diuretics which act more proximally. In treating edematous states, initial therapy with thiazides is effective in most patients who do not exhibit moderate or severe renal insufficiency, severe hyperaldosteronism with excessive distal reabsorption of sodium in exchange for potassium, or excessive sodium reabsorption in the proximal tubule or ascending limb. Nonedematous states in which diuretic therapy is useful include hypertension, hypercalcemia, hypercalciuria, diabetes insipidus, and acute renal failure."} {"id": "PMID:1264897", "title": "Stinging insect allergy: changing concepts.", "content": "Immunologic advances promise changes in the approach to diagnosis and treatment of Hymenoptera stings. Results of skin tests with venom show good correlation with those of in vitro tests (histamine release and radio-allergosorbent test [RAST]). Similar comparisons of whole-body extract (WBE) skin tests with in vitro tests show poor correlation. Treatment emphasis must currently be placed on sting prevention and on medical treatment. The only material now available commercially for immunotherapy is WBE. Circumstantial evidence suggests some benefit from immunotherapy with WBE, but immunologic data do not support this observation.", "contents": "Stinging insect allergy: changing concepts. Immunologic advances promise changes in the approach to diagnosis and treatment of Hymenoptera stings. Results of skin tests with venom show good correlation with those of in vitro tests (histamine release and radio-allergosorbent test [RAST]). Similar comparisons of whole-body extract (WBE) skin tests with in vitro tests show poor correlation. Treatment emphasis must currently be placed on sting prevention and on medical treatment. The only material now available commercially for immunotherapy is WBE. Circumstantial evidence suggests some benefit from immunotherapy with WBE, but immunologic data do not support this observation."} {"id": "PMID:1264899", "title": "Managing obesity: why diet is not enough.", "content": "When the many biologic and societal factors predisposing persons to obesity are considered, it is understandable why traditional therapy so often fails. To be effective, a program of therapy for obesity must include necessary changes in behavior, attitude, and life-style; dieting is not enough. As a first step, the determinants of past and present behaviors contributing to high energy intake, low energy expenditure, or both are identified. Once this is done, therapy is directed toward altering exposure, susceptibility, or response to these determinants.", "contents": "Managing obesity: why diet is not enough. When the many biologic and societal factors predisposing persons to obesity are considered, it is understandable why traditional therapy so often fails. To be effective, a program of therapy for obesity must include necessary changes in behavior, attitude, and life-style; dieting is not enough. As a first step, the determinants of past and present behaviors contributing to high energy intake, low energy expenditure, or both are identified. Once this is done, therapy is directed toward altering exposure, susceptibility, or response to these determinants."} {"id": "PMID:1264907", "title": "Recognizing alcoholism early by physical signs.", "content": "It is hoped that by being alert to clues easily seen on simple inspection, physicians will be more confident in uncovering hidden alcoholism or at least will pursue further any indications in the patient's behavior or history that might lead to early diagnosis and hence to treatment.", "contents": "Recognizing alcoholism early by physical signs. It is hoped that by being alert to clues easily seen on simple inspection, physicians will be more confident in uncovering hidden alcoholism or at least will pursue further any indications in the patient's behavior or history that might lead to early diagnosis and hence to treatment."} {"id": "PMID:1264908", "title": "Assessing drinking problems by history.", "content": "Patients with alcohol problems can be categorized as either medical alcoholics, who have medical problems caused by high levels of alcohol consumption, or behavioral alcoholics, whose drinking results in adverse changes in their behavior. Behavioral alcoholics pose a diagnostic problem to the physician because of their highly developed denial systems. A detailed, accurate drinking history is necessary for diagnostic assessment, and the physician must employ several key strategies in order to circumvent the denial system and elicit relevant information. Additional information can be obtained from a member of the problem drinker's family. Family members should also be involved in the treatment process.", "contents": "Assessing drinking problems by history. Patients with alcohol problems can be categorized as either medical alcoholics, who have medical problems caused by high levels of alcohol consumption, or behavioral alcoholics, whose drinking results in adverse changes in their behavior. Behavioral alcoholics pose a diagnostic problem to the physician because of their highly developed denial systems. A detailed, accurate drinking history is necessary for diagnostic assessment, and the physician must employ several key strategies in order to circumvent the denial system and elicit relevant information. Additional information can be obtained from a member of the problem drinker's family. Family members should also be involved in the treatment process."} {"id": "PMID:1264911", "title": "Diuretics. Use and misuse.", "content": "It is apparent that the large number of diuretics available today enables the clinician to mobilize edema fluid from patients with heart failure or other fluid retention states, to control blood pressure effectively in many patients with hypertension, and to manage many nonedematous states more successfully. The potency of some of these agents and their varied effects on renal tubular transport necessitate a cautious approach based on an understanding of their mechanisms of action. By selectively choosing different diuretics or diuretic combinations, the clinician can achieve the desired diuretic effect and prevent many of the electrolyte and acid-base derangements that accompany diuretic therapy. Selectivity of usage based on knowledge of the practical clinical pharmacology of these agents will also minimize the occurrence of side effects and avoid undesirable drug interactions.", "contents": "Diuretics. Use and misuse. It is apparent that the large number of diuretics available today enables the clinician to mobilize edema fluid from patients with heart failure or other fluid retention states, to control blood pressure effectively in many patients with hypertension, and to manage many nonedematous states more successfully. The potency of some of these agents and their varied effects on renal tubular transport necessitate a cautious approach based on an understanding of their mechanisms of action. By selectively choosing different diuretics or diuretic combinations, the clinician can achieve the desired diuretic effect and prevent many of the electrolyte and acid-base derangements that accompany diuretic therapy. Selectivity of usage based on knowledge of the practical clinical pharmacology of these agents will also minimize the occurrence of side effects and avoid undesirable drug interactions."} {"id": "PMID:1264912", "title": "Antiarrhythmic drugs for ischemic heart disease.", "content": "Therapy with antiarrhythmic drugs may offer the best immediate hope for reducing the large number of deaths due to arrhythmias among patients with ischemic heart disease (IHD). For the prevention of sudden death from ventricular fibrillation, chronic use of these drugs is reasonable in high-risk ambulatory IHD patients, in any patient in whom acute myocardial infarction (MI) is suspected, and in some patients hospitalized for acute MI. However, the effectiveness and possible risks of administering antiarrhythmic drugs in these settings remain essentially unknown. The selection of IHD patients who will benefit most from prophylactic antiarrhythmic drug therapy, the best times for starting and stopping this therapy, and the choice of drug cannot yet be guided by controlled clinical experience. Carefully controlled prospective studies of the beneficial and untoward effects of different drugs in IHD patients are urgently required to provide better guidelines for the clinical use of these potentially life-saving drugs.", "contents": "Antiarrhythmic drugs for ischemic heart disease. Therapy with antiarrhythmic drugs may offer the best immediate hope for reducing the large number of deaths due to arrhythmias among patients with ischemic heart disease (IHD). For the prevention of sudden death from ventricular fibrillation, chronic use of these drugs is reasonable in high-risk ambulatory IHD patients, in any patient in whom acute myocardial infarction (MI) is suspected, and in some patients hospitalized for acute MI. However, the effectiveness and possible risks of administering antiarrhythmic drugs in these settings remain essentially unknown. The selection of IHD patients who will benefit most from prophylactic antiarrhythmic drug therapy, the best times for starting and stopping this therapy, and the choice of drug cannot yet be guided by controlled clinical experience. Carefully controlled prospective studies of the beneficial and untoward effects of different drugs in IHD patients are urgently required to provide better guidelines for the clinical use of these potentially life-saving drugs."} {"id": "PMID:1264913", "title": "Why the angry adolescent?", "content": "The angry behavior of youth today is not a phenomenon but one that is becoming more widespread. The reasons behind it are many and varied. Government commissions formed to review the circumstances and prospects of children in America have repeatedly pointed out the needs of youth, but their recommendations have largely been ignored. That \"we get what we give\" is particularly true in regard to the behavior of our youth. A national commitment must be made to fulfill the basic needs and rights of all young people. They must be given responsibility for their own acts, and the transition from adolescence to adulthood must be facilitated by concerned, caring adults.", "contents": "Why the angry adolescent? The angry behavior of youth today is not a phenomenon but one that is becoming more widespread. The reasons behind it are many and varied. Government commissions formed to review the circumstances and prospects of children in America have repeatedly pointed out the needs of youth, but their recommendations have largely been ignored. That \"we get what we give\" is particularly true in regard to the behavior of our youth. A national commitment must be made to fulfill the basic needs and rights of all young people. They must be given responsibility for their own acts, and the transition from adolescence to adulthood must be facilitated by concerned, caring adults."} {"id": "PMID:1264919", "title": "Traumatic injuries: office treatment of lacerations.", "content": "Every laceration should be explored to its depth to locate foreign bodies and damage to tissues. Debridement should be thorough except on the face, where conservation of skin is important. Deep lacerations are closed in layers, using different sutures for each layer; if tissue has been lost, plastic tecnhiques of closure are necessary. Lacerations that are carefully repaired rarely become infected, and tetanus prophylaxis is the only required safeguard against infection.", "contents": "Traumatic injuries: office treatment of lacerations. Every laceration should be explored to its depth to locate foreign bodies and damage to tissues. Debridement should be thorough except on the face, where conservation of skin is important. Deep lacerations are closed in layers, using different sutures for each layer; if tissue has been lost, plastic tecnhiques of closure are necessary. Lacerations that are carefully repaired rarely become infected, and tetanus prophylaxis is the only required safeguard against infection."} {"id": "PMID:1264920", "title": "Psychiatry: unresolved grief. Clinical considerations.", "content": "Unresolved grief refers either to the absence or to the prolongation of normal grief. It is identified by (1) painful response to recall of the deceased, (2) realization of not having accepted the loss or of not being able to grieve, and (3) unaccountable depression, emergence of medical symptoms on the anniversary of the loss, or both. Three clinical syndromes can be defined in relation to the stage at which the grief process has been arrested. Treatment involves encouraging patients to talk about the deceased and guiding them through a normal grief reaction. Psychiatric evaluation should be considered when suicidal ideation is present.", "contents": "Psychiatry: unresolved grief. Clinical considerations. Unresolved grief refers either to the absence or to the prolongation of normal grief. It is identified by (1) painful response to recall of the deceased, (2) realization of not having accepted the loss or of not being able to grieve, and (3) unaccountable depression, emergence of medical symptoms on the anniversary of the loss, or both. Three clinical syndromes can be defined in relation to the stage at which the grief process has been arrested. Treatment involves encouraging patients to talk about the deceased and guiding them through a normal grief reaction. Psychiatric evaluation should be considered when suicidal ideation is present."} {"id": "PMID:1264956", "title": "An investigation of the incidence of cardiac murmurs in young health women.", "content": "Healthy women students who asked for oral contraceptives were carefully examined to ascertain whether they had a cardiac murmur. Over 52 per cent of the 509 women examined had such a murmur and of these murmurs 3-4 per cent were thought to have an organic origin.", "contents": "An investigation of the incidence of cardiac murmurs in young health women. Healthy women students who asked for oral contraceptives were carefully examined to ascertain whether they had a cardiac murmur. Over 52 per cent of the 509 women examined had such a murmur and of these murmurs 3-4 per cent were thought to have an organic origin."} {"id": "PMID:1264957", "title": "Rubella antibody tests in family planning clinics.", "content": "Women attending for family planning advice at area health authority and general practitioner clinics were offered a test of rubella antibody status. The acceptance rate was approximately 50 per cent. Of the 100 women tested, 15 were not immune and 8 of these were subsequently vaccinated. In this study, the cost of the service was estimated to be 1-50 pounds per woman, or approximately 5000 pounds to prevent one case of congenital rubella. On this basis the assessment of rubella immunity in women using reliable contraception is considered to be feasible and could prove even more worthwhile on a cost-benefit basis if applied to an entirely nulliparous group.", "contents": "Rubella antibody tests in family planning clinics. Women attending for family planning advice at area health authority and general practitioner clinics were offered a test of rubella antibody status. The acceptance rate was approximately 50 per cent. Of the 100 women tested, 15 were not immune and 8 of these were subsequently vaccinated. In this study, the cost of the service was estimated to be 1-50 pounds per woman, or approximately 5000 pounds to prevent one case of congenital rubella. On this basis the assessment of rubella immunity in women using reliable contraception is considered to be feasible and could prove even more worthwhile on a cost-benefit basis if applied to an entirely nulliparous group."} {"id": "PMID:1265008", "title": "Samuel Hyde lecture. Polypharmacy in rheumatoid arthritis--help or hindrance?", "content": "The use of multiple drugs in treating rheumatoid arthritis is based on the assumption that their effects are additive. Sometimes the results are unexpected or the added drug may confer no additional benefit to the patient whilst leaving him more liable to undesirable side-effects. Some form of polypharmacy may be necessitated by the different pharmacological properties of our drugs. Certain drugs have been judged on their steroid-sparing effects allowing lower doses to be used and thereby reducing the toxicity of corticosteroids. It is likely that some potential areas of danger from interacting drugs have been over-emphasized, being based on speculative rather than real data or purely on animal experiments using non-clinical doses. The patient with active RA with a low serum albumin would be unusually susceptible to changes induced by combinations of strongly bound anti-inflammatory drugs. He would also be highly susceptible to side-effects, as has been shown with prednisone. Side-effects here are doubled when the patients serum albumin is below 2.5g/100ml(lewis et al.1971). I believe we should continue to ask ourselves whether by subtracting one or more drugs from the patients cocktail we may not produce a most welcome benefit for both patient and doctor and, I suppose we could even add, the hard-pressed tax payer.", "contents": "Samuel Hyde lecture. Polypharmacy in rheumatoid arthritis--help or hindrance? The use of multiple drugs in treating rheumatoid arthritis is based on the assumption that their effects are additive. Sometimes the results are unexpected or the added drug may confer no additional benefit to the patient whilst leaving him more liable to undesirable side-effects. Some form of polypharmacy may be necessitated by the different pharmacological properties of our drugs. Certain drugs have been judged on their steroid-sparing effects allowing lower doses to be used and thereby reducing the toxicity of corticosteroids. It is likely that some potential areas of danger from interacting drugs have been over-emphasized, being based on speculative rather than real data or purely on animal experiments using non-clinical doses. The patient with active RA with a low serum albumin would be unusually susceptible to changes induced by combinations of strongly bound anti-inflammatory drugs. He would also be highly susceptible to side-effects, as has been shown with prednisone. Side-effects here are doubled when the patients serum albumin is below 2.5g/100ml(lewis et al.1971). I believe we should continue to ask ourselves whether by subtracting one or more drugs from the patients cocktail we may not produce a most welcome benefit for both patient and doctor and, I suppose we could even add, the hard-pressed tax payer."} {"id": "PMID:1265048", "title": "Lipoprotein lipase activity in the bovine corpus luteum during the estrous cycle and early pregnancy.", "content": "Lipolytic activity measured at pH 8.6 in bovine corpora lutea exhibited classical properties of lipoprotein lipase (LPL) in terms of serum and heparin stimulation and NaCl inhibition. LPL activity was measured in 23 corpora lutea collected at different stages of the estrous cycle and early pregnancy. The LPL activity in cyclic corpora lutea (mumole FA released/hr/100 mg acetone powder) was low at Days 4-8 of the estrous cycle (3.1 +/- 1.5: mean +/- SE) and at Days 19-20 (1.6 +/- 0.6). However, high activity of the enzyme was found at Days 12-15 of the cycle (11.8 +/- 1.8); these concentrations were significantly (P less than 0.01) elevated over those found at Days 4-8 and 19-20. The enzyme activity began to decline at Days 16-18 of the estrous cycle (5.1 +/- 1.7). Low enzyme activity was found in the corpora lutea removed from two cows at Day 22 of pregnancy. Progesterone concentrations were measured in 16 of the 23 corpora lutea and a good correlation (r = 0.75, P less than 0.01) was found between lipoprotein lipase and progesterone concentrations of the tissue. The data suggest that LPL may be involved in controlling the transfer of fatty acids, including arachidonic, from plasma lipoproteins to luteal tissue.", "contents": "Lipoprotein lipase activity in the bovine corpus luteum during the estrous cycle and early pregnancy. Lipolytic activity measured at pH 8.6 in bovine corpora lutea exhibited classical properties of lipoprotein lipase (LPL) in terms of serum and heparin stimulation and NaCl inhibition. LPL activity was measured in 23 corpora lutea collected at different stages of the estrous cycle and early pregnancy. The LPL activity in cyclic corpora lutea (mumole FA released/hr/100 mg acetone powder) was low at Days 4-8 of the estrous cycle (3.1 +/- 1.5: mean +/- SE) and at Days 19-20 (1.6 +/- 0.6). However, high activity of the enzyme was found at Days 12-15 of the cycle (11.8 +/- 1.8); these concentrations were significantly (P less than 0.01) elevated over those found at Days 4-8 and 19-20. The enzyme activity began to decline at Days 16-18 of the estrous cycle (5.1 +/- 1.7). Low enzyme activity was found in the corpora lutea removed from two cows at Day 22 of pregnancy. Progesterone concentrations were measured in 16 of the 23 corpora lutea and a good correlation (r = 0.75, P less than 0.01) was found between lipoprotein lipase and progesterone concentrations of the tissue. The data suggest that LPL may be involved in controlling the transfer of fatty acids, including arachidonic, from plasma lipoproteins to luteal tissue."} {"id": "PMID:1265049", "title": "Comparison of dy and dy2J, two alleles expressing forms of muscular dystrophy in the mouse.", "content": "The muscular dystrophies caused by dy and dy2J on a C57BL/6J genetic background are similar in quality. At 1 month, slight differences occur in distribution of the muscle lesions, diffuse and focal, respectively, but at 3 months little, if any, differences exist. The dy dystrophy appears the same histologically on either the C57BL/6J or original 129/ReJ and 129B6F backgrounds.", "contents": "Comparison of dy and dy2J, two alleles expressing forms of muscular dystrophy in the mouse. The muscular dystrophies caused by dy and dy2J on a C57BL/6J genetic background are similar in quality. At 1 month, slight differences occur in distribution of the muscle lesions, diffuse and focal, respectively, but at 3 months little, if any, differences exist. The dy dystrophy appears the same histologically on either the C57BL/6J or original 129/ReJ and 129B6F backgrounds."} {"id": "PMID:1265050", "title": "Differences in survival among germfree mice following transfer to a conventional colony.", "content": "Sex and strain differences in survival were studied in 7-9 month old germfree mice following transfer to a conventional colony. One outbred and three inbred strains were observed. All outbred CD-1 mice survived transfer and in 4 months increased their weight by 50%. The majority of inbred mice survived 7 months after transfer. Sex differences in survival were evident throughout the experimental period and were most marked 7 months after transfer. An unexpected new finding was the viability of the male sex in germfree mice after transfer. Possible explanations are considered.", "contents": "Differences in survival among germfree mice following transfer to a conventional colony. Sex and strain differences in survival were studied in 7-9 month old germfree mice following transfer to a conventional colony. One outbred and three inbred strains were observed. All outbred CD-1 mice survived transfer and in 4 months increased their weight by 50%. The majority of inbred mice survived 7 months after transfer. Sex differences in survival were evident throughout the experimental period and were most marked 7 months after transfer. An unexpected new finding was the viability of the male sex in germfree mice after transfer. Possible explanations are considered."} {"id": "PMID:1265051", "title": "Reduction of experimental myocardial infarct size with hyperosmolar mannitol.", "content": "Hypertonic mannitol previously has been shown to improve cardiac function, increase collateral flow, and decrease epicardial ST segment elevation following coronary occlusion in anesthetized or awake dogs. The present study quantitates by morphologic techniques, the effect of hypertonic mannitol on infarct size. Ischemic injury was produced by proximal occlusion of the circumflex artery for 40 min and necrosis was assessed after 48 hr of reflow. One group of dogs was given isotonic saline and the other hypertonic mannitol beginning the infusions just prior to, during, and for a short period after the release of the circumflex coronary artery occlusion. Serum osmolality increased by approximately 40 mOsm in the mannitol group. The administration of hypertonic mannitol was associated with a 40-50% reduction in infarct size ventricular fibrillation during occlusion and following release of the circumflex coronary artery occlusion was greater in mannitol-treated dogs although the difference was not statistically significant. Thus, the data obtained in this study extend previous observations and provide direct evidence that hypertonic mannitol can reduce infarct size in dogs with temporary circumflex artery occlusion and reflow.", "contents": "Reduction of experimental myocardial infarct size with hyperosmolar mannitol. Hypertonic mannitol previously has been shown to improve cardiac function, increase collateral flow, and decrease epicardial ST segment elevation following coronary occlusion in anesthetized or awake dogs. The present study quantitates by morphologic techniques, the effect of hypertonic mannitol on infarct size. Ischemic injury was produced by proximal occlusion of the circumflex artery for 40 min and necrosis was assessed after 48 hr of reflow. One group of dogs was given isotonic saline and the other hypertonic mannitol beginning the infusions just prior to, during, and for a short period after the release of the circumflex coronary artery occlusion. Serum osmolality increased by approximately 40 mOsm in the mannitol group. The administration of hypertonic mannitol was associated with a 40-50% reduction in infarct size ventricular fibrillation during occlusion and following release of the circumflex coronary artery occlusion was greater in mannitol-treated dogs although the difference was not statistically significant. Thus, the data obtained in this study extend previous observations and provide direct evidence that hypertonic mannitol can reduce infarct size in dogs with temporary circumflex artery occlusion and reflow."} {"id": "PMID:1265052", "title": "Persistent infection of cells in culture by respiratory syncytial virus.", "content": "The virus-cell relationship of RS virus and the HEp-2 cell line has been examined. The production of cytopathic effect (c.p.e.) on HEp-2 cells has been found to be dependent upon the passage level of the cell line. Cells at lower passage levels exhibit c.p.e. in the form of syncytium formation, while those at higher passage levels no longer exhibit this effect. Cells infected at higher passage levels are covertly infected and continue to produce large amounts of infectious virus which remains cell-associated. On continued passage, these cells remain infected with virus but show no c.p.e. and release little if any infectious virus into the medium. Examination of the RNA species present in infected cells revealed that similar species are present in both the overtly and covertly infected cells.", "contents": "Persistent infection of cells in culture by respiratory syncytial virus. The virus-cell relationship of RS virus and the HEp-2 cell line has been examined. The production of cytopathic effect (c.p.e.) on HEp-2 cells has been found to be dependent upon the passage level of the cell line. Cells at lower passage levels exhibit c.p.e. in the form of syncytium formation, while those at higher passage levels no longer exhibit this effect. Cells infected at higher passage levels are covertly infected and continue to produce large amounts of infectious virus which remains cell-associated. On continued passage, these cells remain infected with virus but show no c.p.e. and release little if any infectious virus into the medium. Examination of the RNA species present in infected cells revealed that similar species are present in both the overtly and covertly infected cells."} {"id": "PMID:1265053", "title": "Comparison of effects of prolactin and growth hormone on adrenal 5alpha-reductase in hypophysectomized rats.", "content": "Adrenal 5alpha-reductase activity was measured in female rats 0, 2, 5, and 6 days after hypophysectomy. Enzyme activity increased progressively exhibing a 35-fold elevation at 6 days. The effects of high (250 mug/100 g of body wt), intermediate (25 mug/100 g of body wt), and low (2.5 mug/100 of body wt) daily doses of bovine prolactin and bovine growth hormone were compared at 2 and 5 days posthypophysectomy. At 2 days, enzyme activity was partially inhibited by the high and intermediate doses of prolactin and not affected by growth hormone. At 5 days all doses of prolactin were inhibitory, whereas enzyme activity was suppressed only by the high dose of growth hormone. With a given dose of hormone, the amount of suppression of enzyme activity is greater at 5 days than at 2 days posthypophysectomy. In 5-day hypophysectomized rats the inhibitory effects of prolactin and growth hormone were additive. It is concluded that: (i) hormonal sensitivity and responsiveness of the adrenal reductase pathway increases with duration of pituitary ablation; (ii) the reductive pathway is more sensitive to the effects of prolactin than growth hormone; and (iii) the effects of growth hormone and prolactin on reductase activity are mediated via different mechanisms, as suggested by the additive effects of individual hormones.", "contents": "Comparison of effects of prolactin and growth hormone on adrenal 5alpha-reductase in hypophysectomized rats. Adrenal 5alpha-reductase activity was measured in female rats 0, 2, 5, and 6 days after hypophysectomy. Enzyme activity increased progressively exhibing a 35-fold elevation at 6 days. The effects of high (250 mug/100 g of body wt), intermediate (25 mug/100 g of body wt), and low (2.5 mug/100 of body wt) daily doses of bovine prolactin and bovine growth hormone were compared at 2 and 5 days posthypophysectomy. At 2 days, enzyme activity was partially inhibited by the high and intermediate doses of prolactin and not affected by growth hormone. At 5 days all doses of prolactin were inhibitory, whereas enzyme activity was suppressed only by the high dose of growth hormone. With a given dose of hormone, the amount of suppression of enzyme activity is greater at 5 days than at 2 days posthypophysectomy. In 5-day hypophysectomized rats the inhibitory effects of prolactin and growth hormone were additive. It is concluded that: (i) hormonal sensitivity and responsiveness of the adrenal reductase pathway increases with duration of pituitary ablation; (ii) the reductive pathway is more sensitive to the effects of prolactin than growth hormone; and (iii) the effects of growth hormone and prolactin on reductase activity are mediated via different mechanisms, as suggested by the additive effects of individual hormones."} {"id": "PMID:1265054", "title": "Effect of vitamin B12 and folate on biosynthesis of methionine from homocysteine in the nematode Caenorhabditis briggsae.", "content": "(i) Omission of L-methionine from the medium resulted in an 80% population reduction. Substitution of D,L-homocysteine corrected methionine deficiency in C. briggsae in the presence of supraoptimal vitamin B12 and folic acid. (ii) An absolute vitamin B12 requirement in C. briggsae developed in the medium containing homocysteine at the second subculture. Concentration of 6 ng/ml of vitamin B12 (at 100 ng/ml of folic acid) was sufficient to support maximum growth of C. briggsae in the medium containing homocysteine. (iii) It was found that either supraoptimal folic acid (2000 ng/ml) or supraoptimal vitamin B12 (3750 ng/ml), with homocysteine, supported very little population growth of C. briggsae. However, supraoptimal folic acid and supraoptimal vitamin B12 together supported a maximum population growth. Therefore, it was concluded that both vitamin B12 and folic acid were required for the biosynthesis of methionine from homocysteine. Studies also showed that the two vitamins spared each other for population growth in the medium containing homocysteine.", "contents": "Effect of vitamin B12 and folate on biosynthesis of methionine from homocysteine in the nematode Caenorhabditis briggsae. (i) Omission of L-methionine from the medium resulted in an 80% population reduction. Substitution of D,L-homocysteine corrected methionine deficiency in C. briggsae in the presence of supraoptimal vitamin B12 and folic acid. (ii) An absolute vitamin B12 requirement in C. briggsae developed in the medium containing homocysteine at the second subculture. Concentration of 6 ng/ml of vitamin B12 (at 100 ng/ml of folic acid) was sufficient to support maximum growth of C. briggsae in the medium containing homocysteine. (iii) It was found that either supraoptimal folic acid (2000 ng/ml) or supraoptimal vitamin B12 (3750 ng/ml), with homocysteine, supported very little population growth of C. briggsae. However, supraoptimal folic acid and supraoptimal vitamin B12 together supported a maximum population growth. Therefore, it was concluded that both vitamin B12 and folic acid were required for the biosynthesis of methionine from homocysteine. Studies also showed that the two vitamins spared each other for population growth in the medium containing homocysteine."} {"id": "PMID:1265055", "title": "Evaluation of (14C)aminopyrine clearance for determination of gastric mucosal blood flow.", "content": "This study has demonstrated high correlation between the radiometric and spectrophotometric determinations of gastric mucosal aminopyrine clearance. The radiometric method is technically easier, allows a larger number of samples to be determined and is safer to the subject. The clearance of small amounts of [14C]aminopyrine was unaffected by large doses of unlabeled aminopyrine showing that mucosal extraction is not concentration limited. Small amounts of [14C]aminopyrine may provide an excellent tool for examining the role of mucosal blood flow in the pathogenesis of gastric disease in man.", "contents": "Evaluation of (14C)aminopyrine clearance for determination of gastric mucosal blood flow. This study has demonstrated high correlation between the radiometric and spectrophotometric determinations of gastric mucosal aminopyrine clearance. The radiometric method is technically easier, allows a larger number of samples to be determined and is safer to the subject. The clearance of small amounts of [14C]aminopyrine was unaffected by large doses of unlabeled aminopyrine showing that mucosal extraction is not concentration limited. Small amounts of [14C]aminopyrine may provide an excellent tool for examining the role of mucosal blood flow in the pathogenesis of gastric disease in man."} {"id": "PMID:1265056", "title": "Levamisole augmentation of lymphocyte hyporesponsiveness to phytohaemagglutinin in patients with pulmonary tuberculosis.", "content": "Levamisole has been shown to augment the in vitro responsiveness of lymphocytes to PHA stimulation. The response of lymphocytes of 14 (42%) of 33 patients with pulmonary tuberculosis was augmented by levamisole. Augmentation was observed in 9 (64%) of 14 PHA hyporesponsives lymphocytes and in 5 (26%) of 19 normo-responsive lymphocytes.", "contents": "Levamisole augmentation of lymphocyte hyporesponsiveness to phytohaemagglutinin in patients with pulmonary tuberculosis. Levamisole has been shown to augment the in vitro responsiveness of lymphocytes to PHA stimulation. The response of lymphocytes of 14 (42%) of 33 patients with pulmonary tuberculosis was augmented by levamisole. Augmentation was observed in 9 (64%) of 14 PHA hyporesponsives lymphocytes and in 5 (26%) of 19 normo-responsive lymphocytes."} {"id": "PMID:1265057", "title": "Peripheral plasma progesterone during egg transport in the rabbit.", "content": "Peripheral plasma progesterone concentrations were measured in New Zealand rabbits every 6 hr beginning 12 hr before and continuing until 96 hr after either natural mating, hCG injection, or saline injection. The number of ovulation points in naturally mated animals (9.3 +/- 0.6, mean +/- SE) was not significantly different from that in hCG-injected animals (8.6 +/- 1.5). There was a surge in progesterone secretion following both mating and hCG injection. Plasma progesterone concentrations reached a peak prior to ovulation and then fell to basal levels at the time of ovulation. Beginning at approximately 30 hr after the ovulation-inducing stimulus, there was a progressive, significant (P less than 0.001) increase in plasma progesterone concentration, which continued for the duration of the sampling period. The initiation of the postovulatory increase in progesterone secretion corresponds temporally with the movement of eggs from the ampullary-isthmic junction into the isthmus. The progressive increase in plasma progesterone between 30 and 72 hr after the induction of ovulation corresponds with the gradual movement of eggs through the isthmus into the uterus. The data suggest that movement of eggs through the oviductal isthmus is influenced by the postovulatory secretion of progesterone.", "contents": "Peripheral plasma progesterone during egg transport in the rabbit. Peripheral plasma progesterone concentrations were measured in New Zealand rabbits every 6 hr beginning 12 hr before and continuing until 96 hr after either natural mating, hCG injection, or saline injection. The number of ovulation points in naturally mated animals (9.3 +/- 0.6, mean +/- SE) was not significantly different from that in hCG-injected animals (8.6 +/- 1.5). There was a surge in progesterone secretion following both mating and hCG injection. Plasma progesterone concentrations reached a peak prior to ovulation and then fell to basal levels at the time of ovulation. Beginning at approximately 30 hr after the ovulation-inducing stimulus, there was a progressive, significant (P less than 0.001) increase in plasma progesterone concentration, which continued for the duration of the sampling period. The initiation of the postovulatory increase in progesterone secretion corresponds temporally with the movement of eggs from the ampullary-isthmic junction into the isthmus. The progressive increase in plasma progesterone between 30 and 72 hr after the induction of ovulation corresponds with the gradual movement of eggs through the isthmus into the uterus. The data suggest that movement of eggs through the oviductal isthmus is influenced by the postovulatory secretion of progesterone."} {"id": "PMID:1265058", "title": "The effect of detergent treatment of the gastric mucosa on drug transport.", "content": "The effect of detergent treatment of the canine gastric mucosa on transport of drugs from blood to gastric juice was studied using a chamber technique, in vivo. Detergent treatment was found to increase antipyrine and aminopyrine transport. Facilitation of drug transport was associated with disruption of the gastric mucosal barrier and an increase of aminopyrine clearance.", "contents": "The effect of detergent treatment of the gastric mucosa on drug transport. The effect of detergent treatment of the canine gastric mucosa on transport of drugs from blood to gastric juice was studied using a chamber technique, in vivo. Detergent treatment was found to increase antipyrine and aminopyrine transport. Facilitation of drug transport was associated with disruption of the gastric mucosal barrier and an increase of aminopyrine clearance."} {"id": "PMID:1265059", "title": "Effect of sodium intake on gentamicin nephrotoxicity in the rat.", "content": "Gentamicin nephrotoxicity was examined in rats on normal, high, and low sodium diets. Low sodium diet markedly potentiated nephrotoxic effects of the drug as evidenced by animal mortality, renal failure, pathological changes, and increased renal cortical concentration of the drug. High sodium intake reduced the cortical concentration of gentamicin but renal function and ultrastructure were similar to normally fed rats given in the same dose.", "contents": "Effect of sodium intake on gentamicin nephrotoxicity in the rat. Gentamicin nephrotoxicity was examined in rats on normal, high, and low sodium diets. Low sodium diet markedly potentiated nephrotoxic effects of the drug as evidenced by animal mortality, renal failure, pathological changes, and increased renal cortical concentration of the drug. High sodium intake reduced the cortical concentration of gentamicin but renal function and ultrastructure were similar to normally fed rats given in the same dose."} {"id": "PMID:1265060", "title": "Antigenicity of licensed whole virion and subvirion influenza vaccines in \"high risk\" persons.", "content": "The frequency and magnitude of serum antibody response to type A and B influenza virus induced by whole virion and subvirion vaccines were essentially comparable. Immunization was followed in vaccinated individuals by an antihemagglutinin antibody response to the common antigenic determinant shared by the type A H3N2 viruses. Relatively few individuals developed antibody to the type-specific determinant.", "contents": "Antigenicity of licensed whole virion and subvirion influenza vaccines in \"high risk\" persons. The frequency and magnitude of serum antibody response to type A and B influenza virus induced by whole virion and subvirion vaccines were essentially comparable. Immunization was followed in vaccinated individuals by an antihemagglutinin antibody response to the common antigenic determinant shared by the type A H3N2 viruses. Relatively few individuals developed antibody to the type-specific determinant."} {"id": "PMID:1265061", "title": "Changes in the composition of canine respiratory cells obtained by bronchial lavage following irradiation or drug immunosuppression.", "content": "Canine respiratory cells, obtained by bronchial lavage, and blood leukocytes were monitored to observe cellular changes following acute and chronic immunosuppression. Irradiation (350 R) produced bone marrow suppression and prompt peripheral blood leukopenia, but did not affect recovery of pulmonary alveolar macrophages or lymphocytes for 12 days after. Treatment for 6 weeks with daily methylprednisolone (1 mg/kg) caused a progressive decrease in the number of recoverable respiratory lymphocytes, whereas alternate day methylprednisolone (2 mg/kg) had less effect. Cyclophosphamide in combination with steroids generally augmented the progressive loss of blood and respiratiory lymphocytes. Recovery of alveolar macrophages was not changed appreciably. Thus, the population of lung macrophages, sampled by pulmonary lavage, withstood acute and chronic forms of immunosuppression very well. In contrast, canine lymphocytes seem more susceptible to injury, especially to drug regimens containing steroids.", "contents": "Changes in the composition of canine respiratory cells obtained by bronchial lavage following irradiation or drug immunosuppression. Canine respiratory cells, obtained by bronchial lavage, and blood leukocytes were monitored to observe cellular changes following acute and chronic immunosuppression. Irradiation (350 R) produced bone marrow suppression and prompt peripheral blood leukopenia, but did not affect recovery of pulmonary alveolar macrophages or lymphocytes for 12 days after. Treatment for 6 weeks with daily methylprednisolone (1 mg/kg) caused a progressive decrease in the number of recoverable respiratory lymphocytes, whereas alternate day methylprednisolone (2 mg/kg) had less effect. Cyclophosphamide in combination with steroids generally augmented the progressive loss of blood and respiratiory lymphocytes. Recovery of alveolar macrophages was not changed appreciably. Thus, the population of lung macrophages, sampled by pulmonary lavage, withstood acute and chronic forms of immunosuppression very well. In contrast, canine lymphocytes seem more susceptible to injury, especially to drug regimens containing steroids."} {"id": "PMID:1265062", "title": "Vitamin E supplementation and glutathione peroxidase activity.", "content": "Both excess dietary vitamin E and vitamin E deficiency in rats can significantly depress the activity of GSH peroxidase in liver and plasma of rats. Of all the six levels of vitamin E tested in this study, the dietary level of vitamin E found to maintain the maximum activity of GSH peroxidase in tissues of rats was somewhere between 25 and 250 IU/kg diet. This study conclusively indicates that the excess dietary vitamin E represses GSH peroxidase activity.", "contents": "Vitamin E supplementation and glutathione peroxidase activity. Both excess dietary vitamin E and vitamin E deficiency in rats can significantly depress the activity of GSH peroxidase in liver and plasma of rats. Of all the six levels of vitamin E tested in this study, the dietary level of vitamin E found to maintain the maximum activity of GSH peroxidase in tissues of rats was somewhere between 25 and 250 IU/kg diet. This study conclusively indicates that the excess dietary vitamin E represses GSH peroxidase activity."} {"id": "PMID:1265063", "title": "Transferrin function in zinc absorption and transport.", "content": "Blood was drawn from the portal vein of rats immediately after the insertion of 65Zn into the duodenal lumen. Analysis of the plasma from the portal blood demonstrated that the major portion of absorbed 65Zn was bound to transferrin. When apotransferrin was incubated with 65Zn-labeled basolateral plasma membranes, 60% of the isotope was removed from the membrane. Zinc-free albumin prepared with histidine removed 25% of the 65Zn from labeled membranes and histidine had no effect. These results demonstrate that transferrin functions in the absorption and transport of zinc.", "contents": "Transferrin function in zinc absorption and transport. Blood was drawn from the portal vein of rats immediately after the insertion of 65Zn into the duodenal lumen. Analysis of the plasma from the portal blood demonstrated that the major portion of absorbed 65Zn was bound to transferrin. When apotransferrin was incubated with 65Zn-labeled basolateral plasma membranes, 60% of the isotope was removed from the membrane. Zinc-free albumin prepared with histidine removed 25% of the 65Zn from labeled membranes and histidine had no effect. These results demonstrate that transferrin functions in the absorption and transport of zinc."} {"id": "PMID:1265064", "title": "Effect of diuretics on intestinal transport of electrolytes, glucose, and amino acid.", "content": "The jejunal mucosal membrane of albino mice was used to study the electrical properties and ion transport. The membrane was bathed in Krebs-Ringer solution with or without glucose. When ethacrynic acid (EA), furosemide, or amiloride was added to the bathing fluid of both sides, a transient increase followed by a decrease of both potential difference (PD) and short circuit current (Isc) were observed. In glucose-containing bathing medium, EA inhibited both net Na and Cl flux and residual flux; however, EA had little effect on both Na and Cl flux in glucose-free bathing medium. Studies using everted intestinal sac technique showed that EA inhibited both glucose and L-tyrosine across the mucosal membrane against concentration gradients. Furosemide and amiloride were less potent than EA in inhibiting the Na and Cl flux when the bathing solution contained glucose. But these two compounds had no effect on glucose and L-tyrosine transport across the intestinal mucosa. Furthermore, they did inhibit Cl flux even in the condition of glucose-free bathing medium. It is postulated that all three diuretics act on the brush-border membrane of the intestine. EA probably inhibits the Na-glucose cotransporting system; furosemide and amiloride inhibit the simple diffusion process of Na entry of Cl exit by decreasing the conductance of the membrane.", "contents": "Effect of diuretics on intestinal transport of electrolytes, glucose, and amino acid. The jejunal mucosal membrane of albino mice was used to study the electrical properties and ion transport. The membrane was bathed in Krebs-Ringer solution with or without glucose. When ethacrynic acid (EA), furosemide, or amiloride was added to the bathing fluid of both sides, a transient increase followed by a decrease of both potential difference (PD) and short circuit current (Isc) were observed. In glucose-containing bathing medium, EA inhibited both net Na and Cl flux and residual flux; however, EA had little effect on both Na and Cl flux in glucose-free bathing medium. Studies using everted intestinal sac technique showed that EA inhibited both glucose and L-tyrosine across the mucosal membrane against concentration gradients. Furosemide and amiloride were less potent than EA in inhibiting the Na and Cl flux when the bathing solution contained glucose. But these two compounds had no effect on glucose and L-tyrosine transport across the intestinal mucosa. Furthermore, they did inhibit Cl flux even in the condition of glucose-free bathing medium. It is postulated that all three diuretics act on the brush-border membrane of the intestine. EA probably inhibits the Na-glucose cotransporting system; furosemide and amiloride inhibit the simple diffusion process of Na entry of Cl exit by decreasing the conductance of the membrane."} {"id": "PMID:1265065", "title": "Sex-related difference in antral and serum gastrin levels in the rat.", "content": "Antral and serum gastrin concentrations were found to be significantly lower in female than in male rats. Following ovariectomy, serum gastrin concentration significantly increased to male levels; tissue gastrin also increased, but not significantly. Daily injections of estradiol benzoate (2 mug/day) abolished the rise in gastrin levels after ovariectomy. Antral and serum gastrin concentrations were significantly higher in lactating rats than in any other group tested. The possible relationships among sex-dependent changes in food intake, gastrin concentration, and gastric secretion are discussed.", "contents": "Sex-related difference in antral and serum gastrin levels in the rat. Antral and serum gastrin concentrations were found to be significantly lower in female than in male rats. Following ovariectomy, serum gastrin concentration significantly increased to male levels; tissue gastrin also increased, but not significantly. Daily injections of estradiol benzoate (2 mug/day) abolished the rise in gastrin levels after ovariectomy. Antral and serum gastrin concentrations were significantly higher in lactating rats than in any other group tested. The possible relationships among sex-dependent changes in food intake, gastrin concentration, and gastric secretion are discussed."} {"id": "PMID:1265066", "title": "Capillary density of skeletal muscle in Andean dogs.", "content": "High capillary density and small muscle fiber diameters were found in the sternothyroid muscle of dogs native to 4350 m. The number of capillaries per square millimeter was three times greater while the diameter was less than half of those obtained in the same muscle of normoxic dogs. These findings suggest that tissular adaptative mechanisms are important in the process of acclimatization to hypoxia, contributing to the maintenance of adequate levels of PO2 in the tissue in the presence of hypoxemia.", "contents": "Capillary density of skeletal muscle in Andean dogs. High capillary density and small muscle fiber diameters were found in the sternothyroid muscle of dogs native to 4350 m. The number of capillaries per square millimeter was three times greater while the diameter was less than half of those obtained in the same muscle of normoxic dogs. These findings suggest that tissular adaptative mechanisms are important in the process of acclimatization to hypoxia, contributing to the maintenance of adequate levels of PO2 in the tissue in the presence of hypoxemia."} {"id": "PMID:1265068", "title": "Thyroxine and triiodothyronine influence cultured throid cells: alterations of morphology and mucosubstances.", "content": "Further experimentation with the steer thyroid cell line indicates that the formation of \"follicles\" is enhanced by exposure to 8.9 X 10(-7) M thyroxine (T4) or triiodothyronine (T3) for 96 hr. The production of mucosubstances by the cultured thyroid cells is also increased by treating with T4 or T3, effects demonstrable after staining with PAS-alcian blue at pH 2.5. It is suggested that these in vitro effects bear on morphological organization and synthetic activity of the thyroid gland as well as on autoregulation and intraglandular homeostasis that may occur in situ.", "contents": "Thyroxine and triiodothyronine influence cultured throid cells: alterations of morphology and mucosubstances. Further experimentation with the steer thyroid cell line indicates that the formation of \"follicles\" is enhanced by exposure to 8.9 X 10(-7) M thyroxine (T4) or triiodothyronine (T3) for 96 hr. The production of mucosubstances by the cultured thyroid cells is also increased by treating with T4 or T3, effects demonstrable after staining with PAS-alcian blue at pH 2.5. It is suggested that these in vitro effects bear on morphological organization and synthetic activity of the thyroid gland as well as on autoregulation and intraglandular homeostasis that may occur in situ."} {"id": "PMID:1265069", "title": "Failure of ovalbumin associated with allogeneic spleen ceels to stimulate proliferation of lymph node cells of immune mice.", "content": "Ovalbumin-pulsed spleen cells were found to stimulate thymidine uptake of lymph node cells of syngeneic mice immunized with ovalbumin in complete Freund's adjuvant after treatment of spleen cells with Mitomycin C but not after heating the spleen cells at 56degrees for 30 min. Ovalbumin-pulsed spleen cells of allogeneic mice failed to stimulate the immune lymph node cells more than unpulsed cells, although a net increase in the thymidine uptake above the allogeneic stimulation was observed when free ovalbumin was added to the mixed culture. To eliminate the high background of the mixed lymphocyte reaction, F1 mice were made chimeric with bone marrow of one of the parental strains. Using lymph node cells of the immunized chimeras, the stimulation by pulsed spleen cells was much greater when antigen was presented on cells of the parental strain used for bone marrow injection than when presented on cells of the other parental strain.", "contents": "Failure of ovalbumin associated with allogeneic spleen ceels to stimulate proliferation of lymph node cells of immune mice. Ovalbumin-pulsed spleen cells were found to stimulate thymidine uptake of lymph node cells of syngeneic mice immunized with ovalbumin in complete Freund's adjuvant after treatment of spleen cells with Mitomycin C but not after heating the spleen cells at 56degrees for 30 min. Ovalbumin-pulsed spleen cells of allogeneic mice failed to stimulate the immune lymph node cells more than unpulsed cells, although a net increase in the thymidine uptake above the allogeneic stimulation was observed when free ovalbumin was added to the mixed culture. To eliminate the high background of the mixed lymphocyte reaction, F1 mice were made chimeric with bone marrow of one of the parental strains. Using lymph node cells of the immunized chimeras, the stimulation by pulsed spleen cells was much greater when antigen was presented on cells of the parental strain used for bone marrow injection than when presented on cells of the other parental strain."} {"id": "PMID:1265070", "title": "Decreased venous compliance in dogs with chronic renal hypertension.", "content": "Femoral vein (FV) pressure-volume relationships were measured in vitro in 14 dogs with chronic (more than 4 weeks), one-kidney perinephritic hypertension and in 13 unilaterally nephrectomized normotensive control dogs. Segments of FV were also examined histologically and analyzed for their water and electrolyte contents. Compared to controls: (I) the FV pressure-volume curves of hypertensive dogs were shifted toward the pressure axis (P is less than 0.05); (ii) calcaulated vagous compliance in the pressure range of 0-15 mm Hg was decreased (P is less than 0.05); and (iii) the water and sodium contents of vwins from hypertensive dogs were increased (P is less than 0.05). Histological examination of the FV from hypertensive and control dogs did not reveal significant differences. The findings indicate that the decreases in venous compliance that we have previously observed in the early stages (less than 4 weeks) of perinephritic hypertension in dogs persist into the chronic stage of hypertension. Venous wall \"edema\" may account for the decreased venous compliance in this form of hypertension.", "contents": "Decreased venous compliance in dogs with chronic renal hypertension. Femoral vein (FV) pressure-volume relationships were measured in vitro in 14 dogs with chronic (more than 4 weeks), one-kidney perinephritic hypertension and in 13 unilaterally nephrectomized normotensive control dogs. Segments of FV were also examined histologically and analyzed for their water and electrolyte contents. Compared to controls: (I) the FV pressure-volume curves of hypertensive dogs were shifted toward the pressure axis (P is less than 0.05); (ii) calcaulated vagous compliance in the pressure range of 0-15 mm Hg was decreased (P is less than 0.05); and (iii) the water and sodium contents of vwins from hypertensive dogs were increased (P is less than 0.05). Histological examination of the FV from hypertensive and control dogs did not reveal significant differences. The findings indicate that the decreases in venous compliance that we have previously observed in the early stages (less than 4 weeks) of perinephritic hypertension in dogs persist into the chronic stage of hypertension. Venous wall \"edema\" may account for the decreased venous compliance in this form of hypertension."} {"id": "PMID:1265071", "title": "Inhibition of cholera toxin-stimulated intestinal epithelial cell adenylate cyclase by adenosine analogs.", "content": "The ability of various adenosine analogs to inhibit cholera toxin activation of the intestinal epithelial cell adenylate cyclase-cyclic AMP system was investigated. After incubation of cells with cholera toxin for 6 hr, large increases in cellular cyclic AMP content were observed. Addition of 2', 5'-dideoxyadenosine during the last 30 min of this 6-hr incubation resulted in 70% reduction in elevated cyclic AMP content. Other analogs were not effective inhibitors. 2', 5'-Dideoxyadenosine was also a potent inhibitor of cholera toxin-activated intestinal cell adenylate cyclase activity with half-maximal inhibition occuring at 16 muM. NaF-stimulated cyclase was less susceptible to inhibition. The data suggest that inhibition by 2', 5'-dideoxyadenosine is due at least in part to direct inhibition of the cholera toxin-activated intestinal adenylate cyclase activity.", "contents": "Inhibition of cholera toxin-stimulated intestinal epithelial cell adenylate cyclase by adenosine analogs. The ability of various adenosine analogs to inhibit cholera toxin activation of the intestinal epithelial cell adenylate cyclase-cyclic AMP system was investigated. After incubation of cells with cholera toxin for 6 hr, large increases in cellular cyclic AMP content were observed. Addition of 2', 5'-dideoxyadenosine during the last 30 min of this 6-hr incubation resulted in 70% reduction in elevated cyclic AMP content. Other analogs were not effective inhibitors. 2', 5'-Dideoxyadenosine was also a potent inhibitor of cholera toxin-activated intestinal cell adenylate cyclase activity with half-maximal inhibition occuring at 16 muM. NaF-stimulated cyclase was less susceptible to inhibition. The data suggest that inhibition by 2', 5'-dideoxyadenosine is due at least in part to direct inhibition of the cholera toxin-activated intestinal adenylate cyclase activity."} {"id": "PMID:1265072", "title": "Pleural fluid lysozyme in human disease.", "content": "A prospective study was conducted to define the content, significance, and source of lysozyme present in the pleural fluid in human diseases. The pleural fluid lysozyme activity is similar in various malignant and nonmalignant transudates and exudates, and is of limited diagnostic value. The pleural fluid activity correlated well with that of paired serum samples but it had poor correlation with the disease state, the pleural fluid granulocyte counts, and total white blood cell counts. The data suggest that the pleural fluid lysozyme may be derived primarily from the blood and that it is not the product of inflammatory or neoplastic cells in the fluid itself.", "contents": "Pleural fluid lysozyme in human disease. A prospective study was conducted to define the content, significance, and source of lysozyme present in the pleural fluid in human diseases. The pleural fluid lysozyme activity is similar in various malignant and nonmalignant transudates and exudates, and is of limited diagnostic value. The pleural fluid activity correlated well with that of paired serum samples but it had poor correlation with the disease state, the pleural fluid granulocyte counts, and total white blood cell counts. The data suggest that the pleural fluid lysozyme may be derived primarily from the blood and that it is not the product of inflammatory or neoplastic cells in the fluid itself."} {"id": "PMID:1265073", "title": "Actin associated with membranes of monoamine storage organelles.", "content": "A histo-immunofluorescence technique using anti-actin antibodies has been applied to various subcellular fractions of bovine adrenal medulla and rabbit blood platelets. In the adrenal medulla only the membranes of the chromaffin granules, but not the fractions containing other subcellular particles (microsomes, mitochondria) showed marked immunofluorescence was present in the membranes of the 5-hydroxy-tryptamine organelles as well as in other subcellular particles. It is concluded that in the adrenal medulla, actin is specifically associated with the membranes of the amine storage organelles, whereas in platelets the protein shows a rather general subcellular distribution.", "contents": "Actin associated with membranes of monoamine storage organelles. A histo-immunofluorescence technique using anti-actin antibodies has been applied to various subcellular fractions of bovine adrenal medulla and rabbit blood platelets. In the adrenal medulla only the membranes of the chromaffin granules, but not the fractions containing other subcellular particles (microsomes, mitochondria) showed marked immunofluorescence was present in the membranes of the 5-hydroxy-tryptamine organelles as well as in other subcellular particles. It is concluded that in the adrenal medulla, actin is specifically associated with the membranes of the amine storage organelles, whereas in platelets the protein shows a rather general subcellular distribution."} {"id": "PMID:1265074", "title": "Glucose tolerance, insulin and catecholamine levels in germfree rats.", "content": "Glucose was administered intravenously to 50- and 100-day-old GF and CV rats. Fasting blood glucose levels in GF and CV rats were found to be comparable. Glucose tolerance tests showed that GF and CV rats clear glucose from the blood at a similar rate. Although insulin concentrations in 100-day-old GF rats tended to be somewhat lower than in CV rats, the percentage increase during the 30-min period after glucose administration was similar, and matched the increase in blood glucose. Levels of plasma catecholamines were analyzed fluorometrically and were found to be comparable in 100-day-old GF and CV rats. It was concluded that insulin insufficiency plays no role in the syndrome of metabolic anomalies demonstrated by the germfree rat.", "contents": "Glucose tolerance, insulin and catecholamine levels in germfree rats. Glucose was administered intravenously to 50- and 100-day-old GF and CV rats. Fasting blood glucose levels in GF and CV rats were found to be comparable. Glucose tolerance tests showed that GF and CV rats clear glucose from the blood at a similar rate. Although insulin concentrations in 100-day-old GF rats tended to be somewhat lower than in CV rats, the percentage increase during the 30-min period after glucose administration was similar, and matched the increase in blood glucose. Levels of plasma catecholamines were analyzed fluorometrically and were found to be comparable in 100-day-old GF and CV rats. It was concluded that insulin insufficiency plays no role in the syndrome of metabolic anomalies demonstrated by the germfree rat."} {"id": "PMID:1265076", "title": "Variations in elastaselike esterase activities in human leucocytes during cell maturation.", "content": "Granules of human peripheral blood leucocytes contain four well-characterized elastase isozymes and one or two slow-moving elastaselike esterases (SE) which have not been as well characterized. SE are capable of hydrolyzing typical elastase synthetic sybstrates such as N-acetyl-dl-alanine-alpha-naphthyl ester (Ac-DL-Ala-1-ONap) and N-t-butyloxycarbonyl-L-alanine-p-nitrophenyl ester (Boc-Ala-ONp), but unlike the highly basic elastase isozymes, SE barely migrate into 13% acrylamide gels during cationic electrophoresis at pH 4.3. Hydrolysis of Ac-DL-Ala-1-ONap by SE requires the presence of Triton in the gel, and hydrolysis of Boc-Ala-ONp by the same enzyme(s) is also enhanced in the presence of the detergent. Triton is not required for these activities, in the case of the elastase isozymes. Diisopropylfluorophosphate (Dip-F) inactivates both SE and the elastase isozymes, whereas Ac-(Ala)2-Pro-AlaCH2Cl (a powerful inactivator of the leucocyte elastase isozymes at 10-4 M concentration) does not inactivate SE at the same concentration. Immunochemical studies revealed antigenic cross-reaction between the rapidly migrating leucocyte elastase isozymes and SE. Two preparations of leucocyte granules from nonleukemic bone marrow cells showed no activity of the rapidly migrating elastase isozymes, but did contain SE activity. SE may be a precursor or zymogen form of the elastase isozymes, present in immature cells and partly retained through later stages of development.", "contents": "Variations in elastaselike esterase activities in human leucocytes during cell maturation. Granules of human peripheral blood leucocytes contain four well-characterized elastase isozymes and one or two slow-moving elastaselike esterases (SE) which have not been as well characterized. SE are capable of hydrolyzing typical elastase synthetic sybstrates such as N-acetyl-dl-alanine-alpha-naphthyl ester (Ac-DL-Ala-1-ONap) and N-t-butyloxycarbonyl-L-alanine-p-nitrophenyl ester (Boc-Ala-ONp), but unlike the highly basic elastase isozymes, SE barely migrate into 13% acrylamide gels during cationic electrophoresis at pH 4.3. Hydrolysis of Ac-DL-Ala-1-ONap by SE requires the presence of Triton in the gel, and hydrolysis of Boc-Ala-ONp by the same enzyme(s) is also enhanced in the presence of the detergent. Triton is not required for these activities, in the case of the elastase isozymes. Diisopropylfluorophosphate (Dip-F) inactivates both SE and the elastase isozymes, whereas Ac-(Ala)2-Pro-AlaCH2Cl (a powerful inactivator of the leucocyte elastase isozymes at 10-4 M concentration) does not inactivate SE at the same concentration. Immunochemical studies revealed antigenic cross-reaction between the rapidly migrating leucocyte elastase isozymes and SE. Two preparations of leucocyte granules from nonleukemic bone marrow cells showed no activity of the rapidly migrating elastase isozymes, but did contain SE activity. SE may be a precursor or zymogen form of the elastase isozymes, present in immature cells and partly retained through later stages of development."} {"id": "PMID:1265077", "title": "Correlation of plasma lysosomal enzyme levels with hepatic reticuloendothelial function after trauma.", "content": "Plasma lysosomal enzyme levels and hepatic phagocytosis were determined following Noble-Collip drum trauma in the rat. Circulating cathepsin and acid phosphatase activity increased after sublethal trauma (300 rev), reaching maximal levels at 1-3 hr and returning to pretrauma levels at 24 hr after trauma. Hepatic phagocytosis was decreased maximally at 1 hr and recovered to control levels at 24 hr after sublethal trauma. Increasing trauma intensity (100-500 rev) resulted in a progressive failure in hepatic Kupffer cell phagocytosis and a progressive increase in plasma lysosomal enzyme levels when tested at 60-min post-trauma. A significant inverse correlation was found between the plasma lysosomal enzyme levels and Kupffer cell phagocytosis after trauma. The functional significance of the relationship between these two parameters and its importance in shock survival remain to be determined.", "contents": "Correlation of plasma lysosomal enzyme levels with hepatic reticuloendothelial function after trauma. Plasma lysosomal enzyme levels and hepatic phagocytosis were determined following Noble-Collip drum trauma in the rat. Circulating cathepsin and acid phosphatase activity increased after sublethal trauma (300 rev), reaching maximal levels at 1-3 hr and returning to pretrauma levels at 24 hr after trauma. Hepatic phagocytosis was decreased maximally at 1 hr and recovered to control levels at 24 hr after sublethal trauma. Increasing trauma intensity (100-500 rev) resulted in a progressive failure in hepatic Kupffer cell phagocytosis and a progressive increase in plasma lysosomal enzyme levels when tested at 60-min post-trauma. A significant inverse correlation was found between the plasma lysosomal enzyme levels and Kupffer cell phagocytosis after trauma. The functional significance of the relationship between these two parameters and its importance in shock survival remain to be determined."} {"id": "PMID:1265078", "title": "Effect of fasting and insulin on the glucagon-induced orthophosphate incorporation to the isolated perfused rat liver.", "content": "Isolated perfused fed rat livers spontaneously liberated glucose and orthophosphate to the medium; 24-hr fasted rat livers did not exhibit these phenomena. In perfused fed rat livers, glucagon (2 mug) increased glucose output and promoted orthophosphate incorporation. In perfused fed rat livers, insulin (250 or 500 mU) inhibited the spontaneous liberation of glucose and orthophosphate. Comparable doses of insulin significantly reduced the glucagon (2 mug)-induced increase in glucose output from perfused fed rat liver, but did not affect orthophosphate uptake by the organ.", "contents": "Effect of fasting and insulin on the glucagon-induced orthophosphate incorporation to the isolated perfused rat liver. Isolated perfused fed rat livers spontaneously liberated glucose and orthophosphate to the medium; 24-hr fasted rat livers did not exhibit these phenomena. In perfused fed rat livers, glucagon (2 mug) increased glucose output and promoted orthophosphate incorporation. In perfused fed rat livers, insulin (250 or 500 mU) inhibited the spontaneous liberation of glucose and orthophosphate. Comparable doses of insulin significantly reduced the glucagon (2 mug)-induced increase in glucose output from perfused fed rat liver, but did not affect orthophosphate uptake by the organ."} {"id": "PMID:1265079", "title": "O2 extraction of right and left ventricles.", "content": "O2 extraction was measured simultaneously in right and left ventricles of dogs. Extraction was about 2.5 vol% higher in left ventricle. This figure, together with flow measurements of others (1-3), indicates that VO2/100g is at least twice as great in left ventricle as in right.", "contents": "O2 extraction of right and left ventricles. O2 extraction was measured simultaneously in right and left ventricles of dogs. Extraction was about 2.5 vol% higher in left ventricle. This figure, together with flow measurements of others (1-3), indicates that VO2/100g is at least twice as great in left ventricle as in right."} {"id": "PMID:1265080", "title": "Progesterone synthesis by luteal mitochondria in vitro.", "content": "Mitochondria were prepared from bovine corpora lutea by differential centrifugation and were purified by isopycnic zonal centrifugation. A marked increase in specific cytochrome oxidase activity and a marked decrease in specific DNA and RNA content indicate that the procedure resulted in a highly purified preparation of mitochondria. These organelles had a higher rate of conversion of [4-14C] cholesterol to [4-14C] progesterone than did mitochondria separated only by differential centrifugation, suggesting that luteal mitochondria contain the enzyme systems required for progesterone synthesis.", "contents": "Progesterone synthesis by luteal mitochondria in vitro. Mitochondria were prepared from bovine corpora lutea by differential centrifugation and were purified by isopycnic zonal centrifugation. A marked increase in specific cytochrome oxidase activity and a marked decrease in specific DNA and RNA content indicate that the procedure resulted in a highly purified preparation of mitochondria. These organelles had a higher rate of conversion of [4-14C] cholesterol to [4-14C] progesterone than did mitochondria separated only by differential centrifugation, suggesting that luteal mitochondria contain the enzyme systems required for progesterone synthesis."} {"id": "PMID:1265081", "title": "Effect of intrarenal arterial infusion of magnesium on renin release in dogs.", "content": "Magnesium chloride was infused into the renal artery of anesthetized dogs in order to determine its effect on renal function. Natriuresis and diuresis were observed during MgCl2 infusion, but there appeared to be no effect on glomerular filtration rate (GFR), or plasma sodium or potassium concentrations. Although mean arterial blood pressure and renal plasma flow (RPF) decreased throughout the experiment, the fall was not significant until after stopping MgCl2 infusion. A significant stimulation of renin secretion occurred during magnesium administration.", "contents": "Effect of intrarenal arterial infusion of magnesium on renin release in dogs. Magnesium chloride was infused into the renal artery of anesthetized dogs in order to determine its effect on renal function. Natriuresis and diuresis were observed during MgCl2 infusion, but there appeared to be no effect on glomerular filtration rate (GFR), or plasma sodium or potassium concentrations. Although mean arterial blood pressure and renal plasma flow (RPF) decreased throughout the experiment, the fall was not significant until after stopping MgCl2 infusion. A significant stimulation of renin secretion occurred during magnesium administration."} {"id": "PMID:1265082", "title": "Ammonia formation from glutamine isomers by nonacidotic and acidotic perfused rat kidneys.", "content": "The following points summarize these findings: (i) there are 2 glutamine utilizing enzyme systems in the rat kidney; (ii) the cytoplasmic glutamyltransferase system hydrolyzes either glutamine isomer while the mitochondrial localized glutaminase 1 is specific for the L-isomer; (iii) the cytoplasmic pathway contributes 70% of the total renal ammonia production in the normal kidney; (iv) chronic metabolic acidosis results in a 20-fold activation of the mitochondrial glutaminase 1 pathway.", "contents": "Ammonia formation from glutamine isomers by nonacidotic and acidotic perfused rat kidneys. The following points summarize these findings: (i) there are 2 glutamine utilizing enzyme systems in the rat kidney; (ii) the cytoplasmic glutamyltransferase system hydrolyzes either glutamine isomer while the mitochondrial localized glutaminase 1 is specific for the L-isomer; (iii) the cytoplasmic pathway contributes 70% of the total renal ammonia production in the normal kidney; (iv) chronic metabolic acidosis results in a 20-fold activation of the mitochondrial glutaminase 1 pathway."} {"id": "PMID:1265083", "title": "Release into culture medium of membrane-associated, tumor-specific antigen by B-16 melanoma cells.", "content": "Serum-free supernatant fluids from monolayer cultures of B-16 mouse melanoma cells were found to contain a soluble membrane associated tumor-specific antigen. The 100,000 g supernatant of the culture fluid induced an antibody response to the B-16 cells both in rabbits and in the mouse strain of origin (C57Bl/6J). Similar supernatant fluids derived from an unrelated cell line (L-929) or from normal C57Bl/6 fibroblasts did not contain the B-16 specific material. Preliminary results indicate that the B-16 specific material is a protein of low molecular weight which is released into the culture fluid chiefly by living cells and, to a lesser extent, by autolysing cells.", "contents": "Release into culture medium of membrane-associated, tumor-specific antigen by B-16 melanoma cells. Serum-free supernatant fluids from monolayer cultures of B-16 mouse melanoma cells were found to contain a soluble membrane associated tumor-specific antigen. The 100,000 g supernatant of the culture fluid induced an antibody response to the B-16 cells both in rabbits and in the mouse strain of origin (C57Bl/6J). Similar supernatant fluids derived from an unrelated cell line (L-929) or from normal C57Bl/6 fibroblasts did not contain the B-16 specific material. Preliminary results indicate that the B-16 specific material is a protein of low molecular weight which is released into the culture fluid chiefly by living cells and, to a lesser extent, by autolysing cells."} {"id": "PMID:1265084", "title": "Fluctuations of unbound whole blood polyamine levels during the menstrual cycle.", "content": "Perchloric acid-extractable whole blood spermidine and spermine concentrations were determined over a 4-week period in three men, four women, and one ovariectomized woman. Individual male spermidine/spermine ratios showed little fluctuation and similar values were obtained for each of the three males studied. Male spermidine and spermine concentrations, although stable for each male, varied from one subject to the next. Individual female spermidine/spermine ratios, as well as individual concentrations, fluctuated substantially when compared to those valued obtained for males; female ratios appear to rise and fall as a function of the menstrual cycle. The spermidine/spermine ratios obtained from a normal female receiving oral contraceptive, as well as those from an ovariectomized female, were characteristic of values obtained form men. It is suggested that a sex-related hormone(s) influences sperimidine and spermine concentrations in females.", "contents": "Fluctuations of unbound whole blood polyamine levels during the menstrual cycle. Perchloric acid-extractable whole blood spermidine and spermine concentrations were determined over a 4-week period in three men, four women, and one ovariectomized woman. Individual male spermidine/spermine ratios showed little fluctuation and similar values were obtained for each of the three males studied. Male spermidine and spermine concentrations, although stable for each male, varied from one subject to the next. Individual female spermidine/spermine ratios, as well as individual concentrations, fluctuated substantially when compared to those valued obtained for males; female ratios appear to rise and fall as a function of the menstrual cycle. The spermidine/spermine ratios obtained from a normal female receiving oral contraceptive, as well as those from an ovariectomized female, were characteristic of values obtained form men. It is suggested that a sex-related hormone(s) influences sperimidine and spermine concentrations in females."} {"id": "PMID:1265085", "title": "Inhibitory effect of large doses of propylthiouracil and methimazole on an increase of thyroid radioiodine release in response to thyrotropin.", "content": "Thyroidal radioiodine release increased shortly after a single injection of small doses of PTU, while moderate doses of MMI produced a similar increase of thyroidal radioiodine release with a latency of 7-9 hr. Large doses of PTU and MMI failed to augment thyroidal radioiodine release for at least 29 to 34 hr after the initial administration of goitrogens, although plasma TSH increased significantly because of goitrogen administration. An increase of thyroid hormone release in response to exogenous TSH was depressed by PTU and MMI in rats and mice treated with T4. Since this depression of TSH action only continued for a short period in spite of continuous administration of goitrogens, and since final thyroidal radioiodine release rate was similar to that produced by small doses of PTU, the effects mentioned were not simply due to general toxic action of goitrogens. It is suggested that large doses of PTU and MMI not only block thyroid hormone synthesis but also interfere with the action of TSH on thyroid hormone secretion.", "contents": "Inhibitory effect of large doses of propylthiouracil and methimazole on an increase of thyroid radioiodine release in response to thyrotropin. Thyroidal radioiodine release increased shortly after a single injection of small doses of PTU, while moderate doses of MMI produced a similar increase of thyroidal radioiodine release with a latency of 7-9 hr. Large doses of PTU and MMI failed to augment thyroidal radioiodine release for at least 29 to 34 hr after the initial administration of goitrogens, although plasma TSH increased significantly because of goitrogen administration. An increase of thyroid hormone release in response to exogenous TSH was depressed by PTU and MMI in rats and mice treated with T4. Since this depression of TSH action only continued for a short period in spite of continuous administration of goitrogens, and since final thyroidal radioiodine release rate was similar to that produced by small doses of PTU, the effects mentioned were not simply due to general toxic action of goitrogens. It is suggested that large doses of PTU and MMI not only block thyroid hormone synthesis but also interfere with the action of TSH on thyroid hormone secretion."} {"id": "PMID:1265086", "title": "Evidence for hormonal participation in the natriuretic and kaliuretic responses to intraventricular hypertonic saline and norepinephrine.", "content": "To examine if hypothalamic or pituitary hormones are involved in the induction of the natriuresis which follows the injection of hypertonic saline or norepinephrine into the third ventricle, lesions were placed in the median eminence and the responses to intraventricular norepinephrine or hypertonic saline were evaluated. Sham lesions in which the electrode was lowered into the brain but stopped short of the hypothalamic region did not interfere with the natriuresis, kaliuresis, and antidiuresis induced by the third ventricular injection of either hypertonic sodium chloride or norepinephrine. Lesions in the median eminence which induced diabetes insipidus as evidenced by an increase in water consumption to approximately four times normal completely abolished the natriuresis and kaliuresis in response to intraventricular hypertonic saline or norepinephrine and diminished the antidiuresis. The observations suggest the possibility that a natriuretic hormone(s) is involved in the induction of central natriuresis.", "contents": "Evidence for hormonal participation in the natriuretic and kaliuretic responses to intraventricular hypertonic saline and norepinephrine. To examine if hypothalamic or pituitary hormones are involved in the induction of the natriuresis which follows the injection of hypertonic saline or norepinephrine into the third ventricle, lesions were placed in the median eminence and the responses to intraventricular norepinephrine or hypertonic saline were evaluated. Sham lesions in which the electrode was lowered into the brain but stopped short of the hypothalamic region did not interfere with the natriuresis, kaliuresis, and antidiuresis induced by the third ventricular injection of either hypertonic sodium chloride or norepinephrine. Lesions in the median eminence which induced diabetes insipidus as evidenced by an increase in water consumption to approximately four times normal completely abolished the natriuresis and kaliuresis in response to intraventricular hypertonic saline or norepinephrine and diminished the antidiuresis. The observations suggest the possibility that a natriuretic hormone(s) is involved in the induction of central natriuresis."} {"id": "PMID:1265087", "title": "Alpha-adrenergic regulation of the secretion of an anticomplementary factor in mouse saliva.", "content": "Mouse saliva contains a potent inhibitor of complement activity. The secretion of this inhibitor appears to be regulated by action on alpha-adrenergic receptors for two reasons. First, an alpha-agonist (norepinephrine) elicited saliva with a 260-fold higher specific activity of the inhibitor than that obtained with a cholinergic agent (pilocarpine). Second, the alpha-agonist elicited saliva having 43-foldgreater specific activity than that obtained following administration of a beta-adrenergic agonist (isoproterenol). This anticomplementary factor probably proteolytically degrades one or more of the complement components since it is inhibited by several protease inhibitors. The salivary anticomplementary factor is more potent than trypsin, chymotrypsin, thrombin, or Kallikrein. The anticomplementary factor has a pattern of inhibition like that of Kallikrein but unlike those of trypsin or chymotrypsin.", "contents": "Alpha-adrenergic regulation of the secretion of an anticomplementary factor in mouse saliva. Mouse saliva contains a potent inhibitor of complement activity. The secretion of this inhibitor appears to be regulated by action on alpha-adrenergic receptors for two reasons. First, an alpha-agonist (norepinephrine) elicited saliva with a 260-fold higher specific activity of the inhibitor than that obtained with a cholinergic agent (pilocarpine). Second, the alpha-agonist elicited saliva having 43-foldgreater specific activity than that obtained following administration of a beta-adrenergic agonist (isoproterenol). This anticomplementary factor probably proteolytically degrades one or more of the complement components since it is inhibited by several protease inhibitors. The salivary anticomplementary factor is more potent than trypsin, chymotrypsin, thrombin, or Kallikrein. The anticomplementary factor has a pattern of inhibition like that of Kallikrein but unlike those of trypsin or chymotrypsin."} {"id": "PMID:1265090", "title": "Role of stimulus locale on strain differences in active avoidance after scopolamine of D-amphetamine treatment.", "content": "Three strains of mice were trained in a shuttle avoidance task following treatment with scopolamine (2.0 mg/kg) or d-amphetamine (3.0 mg/kg). When required to run towards light (CS) to avoid shock, A/J mice acquired the response more readily than DBA/2J or C57BL/6J mice. However, when required to run away from the light, the strain differences were eliminated. Under both testing conditions scopolamine and d-amphetamine augmented the performance of A/J mice, but had no effect of even disrupted performance of C57BL/6J. In DBA/2J mice d-amphetamine augmented performance only in the toward condition. Results were interpreted to support the hypothesis that scopolamine and d-amphetamine improve performance by response-disinhibition and response excitation, respectively. The presence of associative difficulties limit the effects of these agents.", "contents": "Role of stimulus locale on strain differences in active avoidance after scopolamine of D-amphetamine treatment. Three strains of mice were trained in a shuttle avoidance task following treatment with scopolamine (2.0 mg/kg) or d-amphetamine (3.0 mg/kg). When required to run towards light (CS) to avoid shock, A/J mice acquired the response more readily than DBA/2J or C57BL/6J mice. However, when required to run away from the light, the strain differences were eliminated. Under both testing conditions scopolamine and d-amphetamine augmented the performance of A/J mice, but had no effect of even disrupted performance of C57BL/6J. In DBA/2J mice d-amphetamine augmented performance only in the toward condition. Results were interpreted to support the hypothesis that scopolamine and d-amphetamine improve performance by response-disinhibition and response excitation, respectively. The presence of associative difficulties limit the effects of these agents."} {"id": "PMID:1265091", "title": "Inhibition of cerebral protein synthesis: performance at different times after passive avoidance training.", "content": "Inhibition of cerebral protein synthesis impairs long-term memory in a variety of species and tasks. Recently it was reported that subcutaneous injection of the protein synthesis inhibitor cycloheximide impaired short-term retention, measured 10 min after training in a passive avoidance task. To examine the possibility that inhibition of cerebral protein synthesis may sometimes disrupt short-term memory, mice were injected subcutaneously with cycloheximide (120 mg/kg) or anisomycin (150 mg/kg), or bitemporally with cycloheximide or anisomycin (100 mug/side) and given one training trial in a passive avoidance box. Subcutaneously injected cycloheximide reduced step-through latencies 10 min after training as reported previously, but anisomycin or bitemporally injected cycloheximide did not. All 4 drug groups exhibited impaired long-term memory. Since the results obtained at short intervals after training varied depending on the drug and route of injection, the impairment produced by subcutaneous cycloheximide at 10 min after training cannot be attributed to inhibition of cerebral protein synthesis. It is suggested that performance at short intervals after training reflects drug side effects on step-through behavior. By contrast, the impairment obtained at long intervals after training is consistent with the hypothesis that cerebral protein synthesis is required for formation of long-term memory.", "contents": "Inhibition of cerebral protein synthesis: performance at different times after passive avoidance training. Inhibition of cerebral protein synthesis impairs long-term memory in a variety of species and tasks. Recently it was reported that subcutaneous injection of the protein synthesis inhibitor cycloheximide impaired short-term retention, measured 10 min after training in a passive avoidance task. To examine the possibility that inhibition of cerebral protein synthesis may sometimes disrupt short-term memory, mice were injected subcutaneously with cycloheximide (120 mg/kg) or anisomycin (150 mg/kg), or bitemporally with cycloheximide or anisomycin (100 mug/side) and given one training trial in a passive avoidance box. Subcutaneously injected cycloheximide reduced step-through latencies 10 min after training as reported previously, but anisomycin or bitemporally injected cycloheximide did not. All 4 drug groups exhibited impaired long-term memory. Since the results obtained at short intervals after training varied depending on the drug and route of injection, the impairment produced by subcutaneous cycloheximide at 10 min after training cannot be attributed to inhibition of cerebral protein synthesis. It is suggested that performance at short intervals after training reflects drug side effects on step-through behavior. By contrast, the impairment obtained at long intervals after training is consistent with the hypothesis that cerebral protein synthesis is required for formation of long-term memory."} {"id": "PMID:1265092", "title": "Chronic delta-9-tetrahydrocannabinol. Transient and lasting effects on avoidance behavior.", "content": "Delta-9-Tetrahydrocannabinol (THC) was administered to albino rats with extensive experience in free-operant (Sidman) lever-press shock avoidance. Dosing (30 mg/kg intragastrically) continued once daily, 3 hr before testing, for 1 to 6 weeks. Significant changes were noted in the response rates of several animals, but both the magnitude and direction of these were highly variable. However, shock rates were reliably elevated by THC, but complete tolerance was observed within 6 sessions. In several rats this was followed by sessions with significantly lower shock rates than the predrug baseline. These rats continued to perform at this level of proficiency until THC was discontinued, at which point the baseline was reacquired. These data emphasize that an important determinant of tolerance to a drug effect is the consequence of the effect for the organism.", "contents": "Chronic delta-9-tetrahydrocannabinol. Transient and lasting effects on avoidance behavior. Delta-9-Tetrahydrocannabinol (THC) was administered to albino rats with extensive experience in free-operant (Sidman) lever-press shock avoidance. Dosing (30 mg/kg intragastrically) continued once daily, 3 hr before testing, for 1 to 6 weeks. Significant changes were noted in the response rates of several animals, but both the magnitude and direction of these were highly variable. However, shock rates were reliably elevated by THC, but complete tolerance was observed within 6 sessions. In several rats this was followed by sessions with significantly lower shock rates than the predrug baseline. These rats continued to perform at this level of proficiency until THC was discontinued, at which point the baseline was reacquired. These data emphasize that an important determinant of tolerance to a drug effect is the consequence of the effect for the organism."} {"id": "PMID:1265093", "title": "Analgesia and hyperractivity following morphine microinjection into mouse brain.", "content": "Analgesia and a paradoxical hyperreactivity to stimuli of sudden onset have recently been reported following the microinjection of morphine into the periacqueductal gray matter of rats. These effects have not been systematically investigated in other species. In the present study, both analgesia and hyperreactivity were observed as dose dependent effects of morphine microinjection into the periacqueductal gray matter of several strains of mice. Analgesia alone was produced by low doses of morphine while at higher doses analgesia was accompanied by hyperreactivity. Strain differences were noted with B6D2F1 mice being more susceptible to the hyperreactivity following morphine than BALB/c mice.", "contents": "Analgesia and hyperractivity following morphine microinjection into mouse brain. Analgesia and a paradoxical hyperreactivity to stimuli of sudden onset have recently been reported following the microinjection of morphine into the periacqueductal gray matter of rats. These effects have not been systematically investigated in other species. In the present study, both analgesia and hyperreactivity were observed as dose dependent effects of morphine microinjection into the periacqueductal gray matter of several strains of mice. Analgesia alone was produced by low doses of morphine while at higher doses analgesia was accompanied by hyperreactivity. Strain differences were noted with B6D2F1 mice being more susceptible to the hyperreactivity following morphine than BALB/c mice."} {"id": "PMID:1265094", "title": "Myocardial sensitivity to catecholamines following exposure of rats to irregular, signalled footshock.", "content": "Emotional stress is associated with an increased activity of both the pituitary-adrenal cortical system and the sympathetic-adrenal medullary systems resulting in raised plasma levels of glucocorticoids and catecholamines. There is evidence to suggest that prolonged stress induced adrenergic hyperactivity initiated myocardial pathogenesis and that this may relate to a corticosteroid catecholamine interaction. In the present study driven atrial strips removed from stressed male CSF rats were found to exhibit an enhanced sensitivity to both norepinephrine and epinephrine. These animals had previously been subjected to irregular foot shock associated with a warning signal; a situation producing a high plasma steroid level. The enhanced myocardial sensitivity to both catecholamines was observed in naive animals subjected to a single period, and persisted unchanged in animals stressed daily over a 28 day period. The hypersensitivity of the myocardium observed immediately after stress was maintained for at least 24 hr, whereas the circulating steroid level had returned to control values within 3 hr. In animals subjected to regular stress without a warning signal, a situation producing a much lower steroid level, no enhanced myocardial sensitivity was observed. While the aetiology of the phenomenon of enhanced myocardial sensitivity to catecholamines is not entirely understood, the evidence presented suggests that it may be related to the extreme elevation of circulating glucocorticoids. The sensitivity of the vas deferens however, was unaltered even though the animals were subjected to the stressor producing a high plasma steroid level. This apparent specifcity of the stress induced sensitivity change is discussed on the basis of receptor differences.", "contents": "Myocardial sensitivity to catecholamines following exposure of rats to irregular, signalled footshock. Emotional stress is associated with an increased activity of both the pituitary-adrenal cortical system and the sympathetic-adrenal medullary systems resulting in raised plasma levels of glucocorticoids and catecholamines. There is evidence to suggest that prolonged stress induced adrenergic hyperactivity initiated myocardial pathogenesis and that this may relate to a corticosteroid catecholamine interaction. In the present study driven atrial strips removed from stressed male CSF rats were found to exhibit an enhanced sensitivity to both norepinephrine and epinephrine. These animals had previously been subjected to irregular foot shock associated with a warning signal; a situation producing a high plasma steroid level. The enhanced myocardial sensitivity to both catecholamines was observed in naive animals subjected to a single period, and persisted unchanged in animals stressed daily over a 28 day period. The hypersensitivity of the myocardium observed immediately after stress was maintained for at least 24 hr, whereas the circulating steroid level had returned to control values within 3 hr. In animals subjected to regular stress without a warning signal, a situation producing a much lower steroid level, no enhanced myocardial sensitivity was observed. While the aetiology of the phenomenon of enhanced myocardial sensitivity to catecholamines is not entirely understood, the evidence presented suggests that it may be related to the extreme elevation of circulating glucocorticoids. The sensitivity of the vas deferens however, was unaltered even though the animals were subjected to the stressor producing a high plasma steroid level. This apparent specifcity of the stress induced sensitivity change is discussed on the basis of receptor differences."} {"id": "PMID:1265095", "title": "Endogenous levels of catecholamines in the rat myocardium following exposure to stress.", "content": "Following exposure of male rats to irregular signalled footshock from which they could escape, the endogenous level of norepinephrine in the myocardium was significantly reduced. In atria the depletion of endogenous norepinephrine was significant following 1 day of stress. This significant depletion was maintained following 4 days of stress but began to return towards control levels by Day 10. A similar, but less pronounced pattern was seen with the ventricles. Little if any epinephrine was detected in both control and stress atria and ventricles. From the results presented it is postulated that irregular signalled footshock results in an inhibition of neuronal uptake.", "contents": "Endogenous levels of catecholamines in the rat myocardium following exposure to stress. Following exposure of male rats to irregular signalled footshock from which they could escape, the endogenous level of norepinephrine in the myocardium was significantly reduced. In atria the depletion of endogenous norepinephrine was significant following 1 day of stress. This significant depletion was maintained following 4 days of stress but began to return towards control levels by Day 10. A similar, but less pronounced pattern was seen with the ventricles. Little if any epinephrine was detected in both control and stress atria and ventricles. From the results presented it is postulated that irregular signalled footshock results in an inhibition of neuronal uptake."} {"id": "PMID:1265096", "title": "Effect of stress on the uptake of 3H-norepinephrine into rat myocardium.", "content": "Spontaneously beating atria from rats previously exposed to irregular, signalled footshock were incubated with 3H-norepinephrine. A significant reduction in the uptake and retention of radioactivity was found in the atria from stressed animals compared with unstressed controls. A kinetic study of the uptake process in both the stressed and control groups showed a similar Km value but a significantly different Vmax. It was concluded that the enhanced myocardial sensitivity to catecholamines previously reported can be explained in part, on the basis of an inhibition of neuronal uptake.", "contents": "Effect of stress on the uptake of 3H-norepinephrine into rat myocardium. Spontaneously beating atria from rats previously exposed to irregular, signalled footshock were incubated with 3H-norepinephrine. A significant reduction in the uptake and retention of radioactivity was found in the atria from stressed animals compared with unstressed controls. A kinetic study of the uptake process in both the stressed and control groups showed a similar Km value but a significantly different Vmax. It was concluded that the enhanced myocardial sensitivity to catecholamines previously reported can be explained in part, on the basis of an inhibition of neuronal uptake."} {"id": "PMID:1265097", "title": "Neurochemical correlates of behavior: levels of amino acids in four areas of the brain of the rat during drug-induced behavioral excitation.", "content": "The levels of GABA, aspartate, glutamate, glycine and alanine were determined in 4 specific brain areas (telencephalon, diencephalon-mesencephalon cerebellum and pons-medulla oblongata) of rats killed during a period of drug-induced behavioral excitation. Behavioral excitation was obtained in adult, male Wistar rats working on a Sidman shock-avoidance schedule following administration of 2 mg/kg tetrabenazine (TBZ) 18 hr after iproniazid (50 mg/kg) pretreatment. When compared to trained animals (working on the avoidance schedule but receiving no drugs), the excited rats had increased levels of GABA in the telencephalon and diencephalon-mesencephalon, decreased levels of aspartate in all 4 brain areas, and a lower content of glycine in the pons-medulla region. The changes in the levels of aspartate in all areas of the brain, GABA in the diencephalon-mesencephalon, and glycine in the pons-medulla were significantly correlated (p less than 0.01) with the degree of excitation. It was observed that avoidance training alone produced increases in the levels of four amino acids: aspartate in telencephalon and cerebellum, GABA in cerebellum, and glycine and glutamate in the pons-medulla. The injection of iproniazid alone or iproniazid followed by TBZ into naive animals had little effect on the levels of the five amino acids. The data are discussed in terms of aspartate and GABA interacting as neurotransmitters with cholinergic and catecholaminergic and/or serotonergic neurons to produced the behavioral excitation.", "contents": "Neurochemical correlates of behavior: levels of amino acids in four areas of the brain of the rat during drug-induced behavioral excitation. The levels of GABA, aspartate, glutamate, glycine and alanine were determined in 4 specific brain areas (telencephalon, diencephalon-mesencephalon cerebellum and pons-medulla oblongata) of rats killed during a period of drug-induced behavioral excitation. Behavioral excitation was obtained in adult, male Wistar rats working on a Sidman shock-avoidance schedule following administration of 2 mg/kg tetrabenazine (TBZ) 18 hr after iproniazid (50 mg/kg) pretreatment. When compared to trained animals (working on the avoidance schedule but receiving no drugs), the excited rats had increased levels of GABA in the telencephalon and diencephalon-mesencephalon, decreased levels of aspartate in all 4 brain areas, and a lower content of glycine in the pons-medulla region. The changes in the levels of aspartate in all areas of the brain, GABA in the diencephalon-mesencephalon, and glycine in the pons-medulla were significantly correlated (p less than 0.01) with the degree of excitation. It was observed that avoidance training alone produced increases in the levels of four amino acids: aspartate in telencephalon and cerebellum, GABA in cerebellum, and glycine and glutamate in the pons-medulla. The injection of iproniazid alone or iproniazid followed by TBZ into naive animals had little effect on the levels of the five amino acids. The data are discussed in terms of aspartate and GABA interacting as neurotransmitters with cholinergic and catecholaminergic and/or serotonergic neurons to produced the behavioral excitation."} {"id": "PMID:1265098", "title": "Role of monoamines in sexual behavior of the female guinea pig.", "content": "Ovariectomized guinea pigs, rendered sexually receptive by injections of estradiol benzoate and progesterone, were treated with drugs that are known to affect monoamine receptor activity. Treatment with the dopamine receptor stimulant apomorphine or the serotonin agonist LSD resulted in a suppression of lordosis behavior that lasted for several hours. The noradrenergic receptor stimulant chlonidine potentiated the performance of lordosis (i.e., increased the duration of individual lordosis responses), while the noradrenergic receptor blocker phenoxybenzamine abolished sexual receptivity. Administration of dopaminergic or serotonergic receptor blockers (pimozide and methysergide, respectively) did not facilitate lordosis. In fact, methysergide produced a brief inhibition of sexual behavior. The results indicate that noradrenergic neurons may be involved in the induction of female sexual behavior in the guinea pig. Dopamine, and possibly serotonin, may serve as transmitters that inhibit lordosis in this species.", "contents": "Role of monoamines in sexual behavior of the female guinea pig. Ovariectomized guinea pigs, rendered sexually receptive by injections of estradiol benzoate and progesterone, were treated with drugs that are known to affect monoamine receptor activity. Treatment with the dopamine receptor stimulant apomorphine or the serotonin agonist LSD resulted in a suppression of lordosis behavior that lasted for several hours. The noradrenergic receptor stimulant chlonidine potentiated the performance of lordosis (i.e., increased the duration of individual lordosis responses), while the noradrenergic receptor blocker phenoxybenzamine abolished sexual receptivity. Administration of dopaminergic or serotonergic receptor blockers (pimozide and methysergide, respectively) did not facilitate lordosis. In fact, methysergide produced a brief inhibition of sexual behavior. The results indicate that noradrenergic neurons may be involved in the induction of female sexual behavior in the guinea pig. Dopamine, and possibly serotonin, may serve as transmitters that inhibit lordosis in this species."} {"id": "PMID:1265099", "title": "Plasma corticosterone following alterations of hypothalamic catecholamines in rats.", "content": "The role of central catecholamines in the regulation of resting ACTH secretion has been investigated by relating plasma corticosterone to changes in hypothalamic catecholamines after treating rats with various amine depleting agents. The hypothesis of a noradrenergic inhibitory control is not supported by the data since a correlation between hypothalamic catecholamine content and plasma corticosterone levels could not be established.", "contents": "Plasma corticosterone following alterations of hypothalamic catecholamines in rats. The role of central catecholamines in the regulation of resting ACTH secretion has been investigated by relating plasma corticosterone to changes in hypothalamic catecholamines after treating rats with various amine depleting agents. The hypothesis of a noradrenergic inhibitory control is not supported by the data since a correlation between hypothalamic catecholamine content and plasma corticosterone levels could not be established."} {"id": "PMID:1265100", "title": "Effect of 10 days reserpine or apomorphine administration on sleep cycles in rats.", "content": "The duration of sleep-wakefulness periods and sleep cycles was investigated by means of EEG and EMG in rats with implanted brain electrodes and myographic electrodes in neck muscles during 5 hr trials after repeated administration of 2 depressant drugs, reserpine and apomorphine. Ten days administration of reserpine at a dose of 0.05 mg/day, SC, decreased the duration of both slow-wave and paradoxical sleep, whereas apomorphine had no effect on sleep duration or occurance of sleep phases in either the low dose (0.2 mg/kg/day, SC) or in the high dose of 0.6 mg/kg/day, SC. This finding might be correlated with previously found differences in catecholamine levels in the brain in the same model experiments.", "contents": "Effect of 10 days reserpine or apomorphine administration on sleep cycles in rats. The duration of sleep-wakefulness periods and sleep cycles was investigated by means of EEG and EMG in rats with implanted brain electrodes and myographic electrodes in neck muscles during 5 hr trials after repeated administration of 2 depressant drugs, reserpine and apomorphine. Ten days administration of reserpine at a dose of 0.05 mg/day, SC, decreased the duration of both slow-wave and paradoxical sleep, whereas apomorphine had no effect on sleep duration or occurance of sleep phases in either the low dose (0.2 mg/kg/day, SC) or in the high dose of 0.6 mg/kg/day, SC. This finding might be correlated with previously found differences in catecholamine levels in the brain in the same model experiments."} {"id": "PMID:1265101", "title": "Dose-related effects of metrazol on retention and EEG.", "content": "The effects of various dose levels of Metrazol on retention and electrocorticogram (ECoG) were investigated. Mice given a subconvulsive 30 mg/kg or a convulsive 50 mg/kg dose of Metrazol 15 min before reversal training in a discriminated escape learning task showed retention impairment of reversal training retention. Lower dose levels (5 or 10 mg/kg) had no effect. The 30 mg/kg dose produced asymmetrical dissociation. The convulsive dose (50 mg/kg), previously reported to result in symmetrical dissociation, produced ECoG changes that were still evident 15 min following the injection, i.e. at the time when training or testing usually took place. With lower doses (10 or 30 mg/kg), no apparent ECoG effects were observed at this interval. The implications of the findings were discussed with respect to the state-dependent hypothesis.", "contents": "Dose-related effects of metrazol on retention and EEG. The effects of various dose levels of Metrazol on retention and electrocorticogram (ECoG) were investigated. Mice given a subconvulsive 30 mg/kg or a convulsive 50 mg/kg dose of Metrazol 15 min before reversal training in a discriminated escape learning task showed retention impairment of reversal training retention. Lower dose levels (5 or 10 mg/kg) had no effect. The 30 mg/kg dose produced asymmetrical dissociation. The convulsive dose (50 mg/kg), previously reported to result in symmetrical dissociation, produced ECoG changes that were still evident 15 min following the injection, i.e. at the time when training or testing usually took place. With lower doses (10 or 30 mg/kg), no apparent ECoG effects were observed at this interval. The implications of the findings were discussed with respect to the state-dependent hypothesis."} {"id": "PMID:1265102", "title": "Drug discrimination in rats: effects of mixtures of ditran and cholinesterase inhibitors.", "content": "Groups of rats were trained in a T-shaped maze to discriminate the effects produced by IP injections of ditran (1.60 mg/kg), either when given singly, or when combined with the acetylcholinesterase inhibitors neostigmine (0.25 mg/kg) or physostigmine (0.50 and 1.00 mg/kg), from the nondrug condition (saline). The results from this state-dependency (StD) model indicated that acquisition of the drug discrimination was similar for the 4 groups of rats. After drug discrimination was established the rats were tested with various drug combinations. Physostigmine (0.50 and 1.00 mg/kg) challenge reversed drug discrimination among rats trained with ditran solely or the ditran plus neostigmine combination. There was no antagonism among the ditran plus physostigmine trained rats. Involvement of the C.N.S. is implicated since tests with neostigmine did not upset ditran discrimination. In addition, survival rate of physostigmine treated mice is increased with ditran. In conclusion, this study indicates the usefulness of employing both training and transfer test procedures when evaluating antagonism in this StD model.", "contents": "Drug discrimination in rats: effects of mixtures of ditran and cholinesterase inhibitors. Groups of rats were trained in a T-shaped maze to discriminate the effects produced by IP injections of ditran (1.60 mg/kg), either when given singly, or when combined with the acetylcholinesterase inhibitors neostigmine (0.25 mg/kg) or physostigmine (0.50 and 1.00 mg/kg), from the nondrug condition (saline). The results from this state-dependency (StD) model indicated that acquisition of the drug discrimination was similar for the 4 groups of rats. After drug discrimination was established the rats were tested with various drug combinations. Physostigmine (0.50 and 1.00 mg/kg) challenge reversed drug discrimination among rats trained with ditran solely or the ditran plus neostigmine combination. There was no antagonism among the ditran plus physostigmine trained rats. Involvement of the C.N.S. is implicated since tests with neostigmine did not upset ditran discrimination. In addition, survival rate of physostigmine treated mice is increased with ditran. In conclusion, this study indicates the usefulness of employing both training and transfer test procedures when evaluating antagonism in this StD model."} {"id": "PMID:1265103", "title": "Conditioned flavor aversions for assessing precipitated morphine abstinence in rats.", "content": "Rats receiving twice-daily morphine injections acquired aversions to a saccharin solution which had been presented for 1 hr immediately prior to injections of naloxone. The degree of aversion was related to the maintenance dosage of morphine. Rats maintained on a regimen of daily saline injections did not show significant aversion to saccharin paired with naloxone, even at doses as high as 40 mg/kg. The sensitivity of the technique was such that significant aversions could be demonstrated in rats receiving doses of morphine as low as 1 mg/kg twice daily. It is suggested that conditioned flavor aversions provide a useful method for assessing the aversive quality of abstinence precipitated from low doses of morphine.", "contents": "Conditioned flavor aversions for assessing precipitated morphine abstinence in rats. Rats receiving twice-daily morphine injections acquired aversions to a saccharin solution which had been presented for 1 hr immediately prior to injections of naloxone. The degree of aversion was related to the maintenance dosage of morphine. Rats maintained on a regimen of daily saline injections did not show significant aversion to saccharin paired with naloxone, even at doses as high as 40 mg/kg. The sensitivity of the technique was such that significant aversions could be demonstrated in rats receiving doses of morphine as low as 1 mg/kg twice daily. It is suggested that conditioned flavor aversions provide a useful method for assessing the aversive quality of abstinence precipitated from low doses of morphine."} {"id": "PMID:1265104", "title": "Effects of frontal polar cortical ablation and cycloheximide on ethanol tolerance in rats.", "content": "Thirty adult male Wister rats were pretrained to criterion on the moving belt test, and then made tolerant to ethanol by daily administration of increasing doses over a period of 3 weeks. After a one-month recovery period, they were divided into 3 groups, subjected to bilateral frontal polar cortical ablations, sham-operation and no operation respectively. After postoperative recovery, the cycle of ethanol treatment and testing was repeated. Only the lesioned group failed to reacquire tolerance. A pilot experiment showed that occipital cortical ablations also prevented tolerance. In a second experiment 32 rats, which had similarly undergone and then recovered from an initial period of ethanol tolerance, were divided into 4 groups which received daily treatment with sucrose plus cycloheximide (0.3 mg/kg), sucrose plus saline, ethanol plus cycloheximide, and ethanol plus saline respectively. Only the ethanol plus saline group re-acquired tolerance. Tt is concluded that frontal polar cortical lesions and cycloheximide can both block the development of tolerance to ethanol in animals previously shown to be capable of developing such tolerance.", "contents": "Effects of frontal polar cortical ablation and cycloheximide on ethanol tolerance in rats. Thirty adult male Wister rats were pretrained to criterion on the moving belt test, and then made tolerant to ethanol by daily administration of increasing doses over a period of 3 weeks. After a one-month recovery period, they were divided into 3 groups, subjected to bilateral frontal polar cortical ablations, sham-operation and no operation respectively. After postoperative recovery, the cycle of ethanol treatment and testing was repeated. Only the lesioned group failed to reacquire tolerance. A pilot experiment showed that occipital cortical ablations also prevented tolerance. In a second experiment 32 rats, which had similarly undergone and then recovered from an initial period of ethanol tolerance, were divided into 4 groups which received daily treatment with sucrose plus cycloheximide (0.3 mg/kg), sucrose plus saline, ethanol plus cycloheximide, and ethanol plus saline respectively. Only the ethanol plus saline group re-acquired tolerance. Tt is concluded that frontal polar cortical lesions and cycloheximide can both block the development of tolerance to ethanol in animals previously shown to be capable of developing such tolerance."} {"id": "PMID:1265105", "title": "Intracranial cycloheximide: effect on male mouse sexual behavior and plasma testosterone.", "content": "Cycloheximide (Cyclo), an inhibitor of protein synthesis, infused bilaterally into the preoptic area (POA) of intact B6D2F male mice significantly inhibited male sexual behavior when the males were presented with receptive females 12 hr after treatment. The few males that ejaculated appeared to copulate normally. This finding suggests that Cyclo acts primarily by inhibiting sexual arousal rather than sexual performance. The inhibition of sexual behavior was not observed when the males were tested 84 hr after treatment. After exposure to an estrous female, plasma testosterone levels were measured in males with POA infusions of Cyclo or saline vehicle. No significant difference was found, but both groups had significantly higher levels of plasma testosterone than males not exposed to estrous females. It is suggested that the interference with sexual behavior by Cyclo was not due to interference with the neuroendocrine mechanisms controlling blood andorgen levels, but due to Cyclo acting directly on the neural circuits controlling sexual responsiveness.", "contents": "Intracranial cycloheximide: effect on male mouse sexual behavior and plasma testosterone. Cycloheximide (Cyclo), an inhibitor of protein synthesis, infused bilaterally into the preoptic area (POA) of intact B6D2F male mice significantly inhibited male sexual behavior when the males were presented with receptive females 12 hr after treatment. The few males that ejaculated appeared to copulate normally. This finding suggests that Cyclo acts primarily by inhibiting sexual arousal rather than sexual performance. The inhibition of sexual behavior was not observed when the males were tested 84 hr after treatment. After exposure to an estrous female, plasma testosterone levels were measured in males with POA infusions of Cyclo or saline vehicle. No significant difference was found, but both groups had significantly higher levels of plasma testosterone than males not exposed to estrous females. It is suggested that the interference with sexual behavior by Cyclo was not due to interference with the neuroendocrine mechanisms controlling blood andorgen levels, but due to Cyclo acting directly on the neural circuits controlling sexual responsiveness."} {"id": "PMID:1265106", "title": "Behavioral teratogenesis: a critical evaluation.", "content": "A critical review of some relevant literature concerning the effects of prenatal administration of drugs and several other substances on postnatal behavior. Significant variables and problems in the adequate design of experiments to assess these effects are discussed. Although the evidence concerning prenatal drug effects on behavior is equivocal, sufficient data exist to indicate that this will continue to be a viable and important area of research in the future. Present results demonstrate the complexity of drug interactions with other variables.", "contents": "Behavioral teratogenesis: a critical evaluation. A critical review of some relevant literature concerning the effects of prenatal administration of drugs and several other substances on postnatal behavior. Significant variables and problems in the adequate design of experiments to assess these effects are discussed. Although the evidence concerning prenatal drug effects on behavior is equivocal, sufficient data exist to indicate that this will continue to be a viable and important area of research in the future. Present results demonstrate the complexity of drug interactions with other variables."} {"id": "PMID:1265107", "title": "Pitressin-induced inhibition of drinking following water deprivation in the SWR/J mouse.", "content": "SWR/J female mice, 8 hr water deprived, were injected intraperitoneally with 0, 10, 50, 200, and 800 mU of aqueous pitressin, 5 min prior to presentation of water. Drinking measurements made at 5, 15, 25, and 35 min of the drinking period revealed a significant transient inhibition of drinking for the three highest dosages. Injections had no measureable effect on blood pressure. Only the highest dosage had an effect on gross motor activity, a significant decline.", "contents": "Pitressin-induced inhibition of drinking following water deprivation in the SWR/J mouse. SWR/J female mice, 8 hr water deprived, were injected intraperitoneally with 0, 10, 50, 200, and 800 mU of aqueous pitressin, 5 min prior to presentation of water. Drinking measurements made at 5, 15, 25, and 35 min of the drinking period revealed a significant transient inhibition of drinking for the three highest dosages. Injections had no measureable effect on blood pressure. Only the highest dosage had an effect on gross motor activity, a significant decline."} {"id": "PMID:1265108", "title": "Drug-induced conditioned suppression: specificity due to drug employed as UCS.", "content": "The classical conditioning potential of several drugs was tested in rats by pairing a light CS with the drug UCSs; these stimuli were superimposed in a variable-interval 30 sec schedule for water reinforcement. Conditioning (suppression of bar-pressing in the presence of the CS) was definitely demonstrated with psilocybin (2.0 mg/kg), was suggested but not clearly shown with LSD (0.13 MG/kg), and was not evident with methyl atropine nitrate (50 mg/kg) or pentobarbital (25 mg/kg). These results indicate that previously demonstrated drug-induced conditioned suppression is not a nonspecific effect of unconditioned suppression but depends on the type of drug employed.", "contents": "Drug-induced conditioned suppression: specificity due to drug employed as UCS. The classical conditioning potential of several drugs was tested in rats by pairing a light CS with the drug UCSs; these stimuli were superimposed in a variable-interval 30 sec schedule for water reinforcement. Conditioning (suppression of bar-pressing in the presence of the CS) was definitely demonstrated with psilocybin (2.0 mg/kg), was suggested but not clearly shown with LSD (0.13 MG/kg), and was not evident with methyl atropine nitrate (50 mg/kg) or pentobarbital (25 mg/kg). These results indicate that previously demonstrated drug-induced conditioned suppression is not a nonspecific effect of unconditioned suppression but depends on the type of drug employed."} {"id": "PMID:1265109", "title": "Treatment of lumbar disks with chymopapain.", "content": "Symptoms arising from a herniated disk appear when the nucleus pulposus or soft inner portion of the disk bulges against a nerve root. When conservative treatment fails to help the patient, the enzyme chymopapain is currently being used in the treatment of such conditions. Injected directly into the disk, the chymopapain dissolves the nucleus by enzymatic action which selectively breaks certain bonds within the nucleus. The pressure within the center is decreased, hence the pressure against the nerve root is relieved, alleviating the symptoms. Because back care is particularly important following such treatment, physical therapy is valuable in promoting continued relief. The major emphasis of the therapy back care program is on abdominal strengthening exercises and postural training.", "contents": "Treatment of lumbar disks with chymopapain. Symptoms arising from a herniated disk appear when the nucleus pulposus or soft inner portion of the disk bulges against a nerve root. When conservative treatment fails to help the patient, the enzyme chymopapain is currently being used in the treatment of such conditions. Injected directly into the disk, the chymopapain dissolves the nucleus by enzymatic action which selectively breaks certain bonds within the nucleus. The pressure within the center is decreased, hence the pressure against the nerve root is relieved, alleviating the symptoms. Because back care is particularly important following such treatment, physical therapy is valuable in promoting continued relief. The major emphasis of the therapy back care program is on abdominal strengthening exercises and postural training."} {"id": "PMID:1265110", "title": "Effect of circuit exercise training on physical fitness of alcoholic patients.", "content": "A group of patients with chronic alcoholism who participated in a circuit training exercise program were compared on a stair climbing task to a group of patients who did not participate in the program. After three weeks, the patients in the exercise group had gained significantly in the number of stairs which they could climb when compared to the patients in the nonexercise group. The time required to return to the heart rate before stair climbing was significantly shorter for exercising patients than for nonexercising patients. The circuit training exercise program, therefore, appears to be an effective method for improving the fitness level of alcoholic patients.", "contents": "Effect of circuit exercise training on physical fitness of alcoholic patients. A group of patients with chronic alcoholism who participated in a circuit training exercise program were compared on a stair climbing task to a group of patients who did not participate in the program. After three weeks, the patients in the exercise group had gained significantly in the number of stairs which they could climb when compared to the patients in the nonexercise group. The time required to return to the heart rate before stair climbing was significantly shorter for exercising patients than for nonexercising patients. The circuit training exercise program, therefore, appears to be an effective method for improving the fitness level of alcoholic patients."} {"id": "PMID:1265111", "title": "Research and human rights. Part 1.", "content": "The problem of biomedical research and human rights is reviewed from the perspectives of current issues, historical events, and other sciences. Government control of research, reactions to and possible consequences of that control, and the concern for consent from members of vulnerable populations are examined. The nature of research is discussed and the origins of opposing ethical views are described in an attempt to clarify the issues within the problem.", "contents": "Research and human rights. Part 1. The problem of biomedical research and human rights is reviewed from the perspectives of current issues, historical events, and other sciences. Government control of research, reactions to and possible consequences of that control, and the concern for consent from members of vulnerable populations are examined. The nature of research is discussed and the origins of opposing ethical views are described in an attempt to clarify the issues within the problem."} {"id": "PMID:1265112", "title": "Physical therapy following disconnection of the cerebral hemispheres.", "content": "An alternative available for the patient with intractable epilepsy is disconnection of the cerebral hemispheres. The role of the physical therapist includes evaluating motor loss and establishing a program based on the evaluation which stresses balance, coordination, endurance, and accommodation for inattention in the left visual field. The program extends to the home situation with follow-up testing after discharge. No long-standing motor problems were evident other than lack of ability to carry out rapid highly coordinated activities. Six months after surgery the patients had returned to school, jobs, family responsibilities, or special care and were discharged from physical therapy.", "contents": "Physical therapy following disconnection of the cerebral hemispheres. An alternative available for the patient with intractable epilepsy is disconnection of the cerebral hemispheres. The role of the physical therapist includes evaluating motor loss and establishing a program based on the evaluation which stresses balance, coordination, endurance, and accommodation for inattention in the left visual field. The program extends to the home situation with follow-up testing after discharge. No long-standing motor problems were evident other than lack of ability to carry out rapid highly coordinated activities. Six months after surgery the patients had returned to school, jobs, family responsibilities, or special care and were discharged from physical therapy."} {"id": "PMID:1265117", "title": "Multidisciplinary approach to sex education of spinal cord-injured patients.", "content": "The need for sex education of spinal cord-injured patients is often unmet by current rehabilitation programs. In the programs which do exist, therapeutic objectives vary widely, indicating a need for clarity and communication among professionals. An interdisciplinary approach to evaluating and treating sexual dysfunction is described which provides information to patients and families about sexual disorders related to spinal injury and offers counseling services to patients experiencing problems in their altered sex relations. Physiological, psychological, and social aspects of human sexuality as they are integrated into a multidisciplinary sex education program are discussed with specific recommendations for content which should be included in the information-giving counseling process.", "contents": "Multidisciplinary approach to sex education of spinal cord-injured patients. The need for sex education of spinal cord-injured patients is often unmet by current rehabilitation programs. In the programs which do exist, therapeutic objectives vary widely, indicating a need for clarity and communication among professionals. An interdisciplinary approach to evaluating and treating sexual dysfunction is described which provides information to patients and families about sexual disorders related to spinal injury and offers counseling services to patients experiencing problems in their altered sex relations. Physiological, psychological, and social aspects of human sexuality as they are integrated into a multidisciplinary sex education program are discussed with specific recommendations for content which should be included in the information-giving counseling process."} {"id": "PMID:1265119", "title": "Stability and comparability of intellectual measures for cerebral-palsied preschoolers.", "content": "Intelligence test scores on the Stanford-Binet Intelligence Scale and the Merrill Palmer Scale were studied for 23 cerebral-palsied children to determine the stability and comparability of these measures during the preschool years as well as the relationship of pyschological gains or losses to clinical diagnoses of the children. Test and posttest data were analyzed for subjects who had participated for one year in a special preschool program for children with neuromotor problems. A high correlation was found between the two intelligence tests both on pretesting (r = .89) and posttesting (r = .83). No significant differences were observed between IQs attained at the three-year level and IQs attained at the four-year level. No associative pattern between etiology of the disability, neuromotor involvement, and intelligence test patterns was determined.", "contents": "Stability and comparability of intellectual measures for cerebral-palsied preschoolers. Intelligence test scores on the Stanford-Binet Intelligence Scale and the Merrill Palmer Scale were studied for 23 cerebral-palsied children to determine the stability and comparability of these measures during the preschool years as well as the relationship of pyschological gains or losses to clinical diagnoses of the children. Test and posttest data were analyzed for subjects who had participated for one year in a special preschool program for children with neuromotor problems. A high correlation was found between the two intelligence tests both on pretesting (r = .89) and posttesting (r = .83). No significant differences were observed between IQs attained at the three-year level and IQs attained at the four-year level. No associative pattern between etiology of the disability, neuromotor involvement, and intelligence test patterns was determined."} {"id": "PMID:1265120", "title": "Continuing Education Unit: a new dimension in continuing education.", "content": "The rapid expansion of continuing education within the professions has evolved with little continuity and structure, a fact which impedes the professional's ability to develop a long-range plan of continued professional development. A major weakness stems from society's lack of uniform standards to measure and certify continuing education. A new unit of measure, the continuing education unit (CEU), has been developed as a voluntary national effort for a uniform unit of measure for noncredit continuing education, which will both quantify programs and ensure a reasonable degree of program quality. Effective implementation and use of the CEU requires consumers of continuing education to assume a greater role in program planning and development in conjunction with program producers. The CEU provides a valuable tool for the professions to effectively use continuing education; however, improved competency requires more than the mere accumulation of CEU.", "contents": "Continuing Education Unit: a new dimension in continuing education. The rapid expansion of continuing education within the professions has evolved with little continuity and structure, a fact which impedes the professional's ability to develop a long-range plan of continued professional development. A major weakness stems from society's lack of uniform standards to measure and certify continuing education. A new unit of measure, the continuing education unit (CEU), has been developed as a voluntary national effort for a uniform unit of measure for noncredit continuing education, which will both quantify programs and ensure a reasonable degree of program quality. Effective implementation and use of the CEU requires consumers of continuing education to assume a greater role in program planning and development in conjunction with program producers. The CEU provides a valuable tool for the professions to effectively use continuing education; however, improved competency requires more than the mere accumulation of CEU."} {"id": "PMID:1265156", "title": "Behavioral treatment of hysterical neurosis: symptom substitution and sympton return reconsidered.", "content": "One of the major areas of disagreement between therapists working within the psychodynamic and behavioral frameworks involves the issues of symptom substitution and symptom return, the psychodynamicists holding that treatment of symptoms alone cannot result in permanent improvement, and the behavioral therapists arguing that it can. However, a reexamination of the data indicates that psychoanalysts base their conclusions primarily on cases of hysterical neurosis whereas the behaviorists base their conclusions primarily on the treatment of phobia. Heeding the call of the recent American Psychiatric Association Task Force on Behavior Therapy (1973), in this paper we seek to reconcile the apparently contradictory data, illustrating our arguments with case reports. Moreover, we will attempt to obtain a greater degree of rapprochement and cross-fertilization between the dynamic and behavioral schools of thought.", "contents": "Behavioral treatment of hysterical neurosis: symptom substitution and sympton return reconsidered. One of the major areas of disagreement between therapists working within the psychodynamic and behavioral frameworks involves the issues of symptom substitution and symptom return, the psychodynamicists holding that treatment of symptoms alone cannot result in permanent improvement, and the behavioral therapists arguing that it can. However, a reexamination of the data indicates that psychoanalysts base their conclusions primarily on cases of hysterical neurosis whereas the behaviorists base their conclusions primarily on the treatment of phobia. Heeding the call of the recent American Psychiatric Association Task Force on Behavior Therapy (1973), in this paper we seek to reconcile the apparently contradictory data, illustrating our arguments with case reports. Moreover, we will attempt to obtain a greater degree of rapprochement and cross-fertilization between the dynamic and behavioral schools of thought."} {"id": "PMID:1265159", "title": "Time and Schizophrenia.", "content": "It is possible, albeit reductionistic, to consider the many dysfunctions of reality testing found in schizophrenia as manifestations of a defective time sense. This perspective on schizophrenic discourse, for instance, permits a new grasp of \"schizophrenic logic\" and a novel approach to therapeutic interpretation. The present paper describes the use of time-related interventions in the psychotherapy of a schizophrenic patient. Several aspects of time sense are outlined. Under each heading are examples from the psychotherapy of Carrie, demonstrating her idiosyncratic notion of that particular temporal concept. Interpretations are aimed at clarifying the cognitive assumptions underlying the patient's expressions.", "contents": "Time and Schizophrenia. It is possible, albeit reductionistic, to consider the many dysfunctions of reality testing found in schizophrenia as manifestations of a defective time sense. This perspective on schizophrenic discourse, for instance, permits a new grasp of \"schizophrenic logic\" and a novel approach to therapeutic interpretation. The present paper describes the use of time-related interventions in the psychotherapy of a schizophrenic patient. Several aspects of time sense are outlined. Under each heading are examples from the psychotherapy of Carrie, demonstrating her idiosyncratic notion of that particular temporal concept. Interpretations are aimed at clarifying the cognitive assumptions underlying the patient's expressions."} {"id": "PMID:1265236", "title": "Routine tomography of the temporomandibular joint.", "content": "Routine lateral tomography of the temporomandibular joint has resulted in a three-fold increase in the detection of positive findings. The technique is easily accomplished, eliminates the problem of superimposition of unwanted structures, permits a true lateral view of the condyle and condylar fossa, and allows small articular surface abnormalities to be identified. Although the entrance skin dose to the patient's face in the beam is about two times greater per exposure than that for our previous conventional open and closed lateral views, we believe that the increased dose is reasonable and the resulting improved diagnostic accuracy outweighs this disadvantage.", "contents": "Routine tomography of the temporomandibular joint. Routine lateral tomography of the temporomandibular joint has resulted in a three-fold increase in the detection of positive findings. The technique is easily accomplished, eliminates the problem of superimposition of unwanted structures, permits a true lateral view of the condyle and condylar fossa, and allows small articular surface abnormalities to be identified. Although the entrance skin dose to the patient's face in the beam is about two times greater per exposure than that for our previous conventional open and closed lateral views, we believe that the increased dose is reasonable and the resulting improved diagnostic accuracy outweighs this disadvantage."} {"id": "PMID:1265240", "title": "The evaluation of tracheal abnormalities by tomography.", "content": "At present, linear plain-film tomography of the trachea is the method of choice for demonstrating the location of post-tracheostomy stenotic lesions and tracheal tumors. This technique does not further compromise the patient's respiratory status, as sometimes occurs with positive-contrast studies using iodine-containing materials, and the radiation dose to the patient from plain-film tomography is considerably less than that from xerotomography.", "contents": "The evaluation of tracheal abnormalities by tomography. At present, linear plain-film tomography of the trachea is the method of choice for demonstrating the location of post-tracheostomy stenotic lesions and tracheal tumors. This technique does not further compromise the patient's respiratory status, as sometimes occurs with positive-contrast studies using iodine-containing materials, and the radiation dose to the patient from plain-film tomography is considerably less than that from xerotomography."} {"id": "PMID:1265241", "title": "Teaching English composition to radiologic technologists: You don't need to read Hamlet.", "content": "As the allied health degree programs move from the locus of the hospital to the college campus, the administrators and students concerned with technical curriculums are often confronted with an inexorable freshman composition requirement. However, a special course was developed for the radiologic technology program at Morris Harvey College in Charleston, West Virginia. The following article details a one-semester course plan that anyone who is currently teaching English can adapt to make freshman composition practical for those students who are not enrolled in liberal arts degree programs.", "contents": "Teaching English composition to radiologic technologists: You don't need to read Hamlet. As the allied health degree programs move from the locus of the hospital to the college campus, the administrators and students concerned with technical curriculums are often confronted with an inexorable freshman composition requirement. However, a special course was developed for the radiologic technology program at Morris Harvey College in Charleston, West Virginia. The following article details a one-semester course plan that anyone who is currently teaching English can adapt to make freshman composition practical for those students who are not enrolled in liberal arts degree programs."} {"id": "PMID:1265247", "title": "Left ventricular angiocardiography in coronary artery disease.", "content": "Cineangiocardiography is a clinically important method for studying the left ventricle in coronary artery disease. However, at present left ventricular angiocardiography is only a semiquantitative method. This is important to bear in mind when making decision on treatment, prognosis and follow up of patients. Various techniques to improve the diagnostic value of left ventricular angiocardiography and make it a quantitative method have been suggested and they should be applied in patients in carefully planned studies to determine their clinical value.", "contents": "Left ventricular angiocardiography in coronary artery disease. Cineangiocardiography is a clinically important method for studying the left ventricle in coronary artery disease. However, at present left ventricular angiocardiography is only a semiquantitative method. This is important to bear in mind when making decision on treatment, prognosis and follow up of patients. Various techniques to improve the diagnostic value of left ventricular angiocardiography and make it a quantitative method have been suggested and they should be applied in patients in carefully planned studies to determine their clinical value."} {"id": "PMID:1265248", "title": "[Morphology of coronary heart disease (author's transl)].", "content": "Atherosclerosis and insufficiency of the coronary arteries and their sequelae are summarized in the term \"coronary heart disease\". For the evaluation of the coronary arteries the knowledge of malformations, variants and supply areas is of importance. Extension and severity of atherosclerosis of the coronary arteries and their insufficiency is being influenced by hyperlipidemia, hypertension and diabetes mellitus. The process of atherosclerosis as a cause of the proliferation of vascular smooth muscle cells in complicated by ulceration, parietal and obliterative thrombosis as well by intramural hemorrhages. Relative ischemia leeds to disseminated cell necrosis; total ischemia causes large myocardial tissue necrosis, called infarction. Localization and extension of infarction and the later scars correspond to the caliber of the obliterated coronary artery and to the significance of the collaterals. Postmortem coronary angiography can detect cause and extension of the damaged cardiac area. Functional significance of chronic coronary heart disease is related to the \"critical connective tissue content\" of the heart. After surgical treatment qualitative and quantitative morphology may help to explain postoperative cardiac failure.", "contents": "[Morphology of coronary heart disease (author's transl)]. Atherosclerosis and insufficiency of the coronary arteries and their sequelae are summarized in the term \"coronary heart disease\". For the evaluation of the coronary arteries the knowledge of malformations, variants and supply areas is of importance. Extension and severity of atherosclerosis of the coronary arteries and their insufficiency is being influenced by hyperlipidemia, hypertension and diabetes mellitus. The process of atherosclerosis as a cause of the proliferation of vascular smooth muscle cells in complicated by ulceration, parietal and obliterative thrombosis as well by intramural hemorrhages. Relative ischemia leeds to disseminated cell necrosis; total ischemia causes large myocardial tissue necrosis, called infarction. Localization and extension of infarction and the later scars correspond to the caliber of the obliterated coronary artery and to the significance of the collaterals. Postmortem coronary angiography can detect cause and extension of the damaged cardiac area. Functional significance of chronic coronary heart disease is related to the \"critical connective tissue content\" of the heart. After surgical treatment qualitative and quantitative morphology may help to explain postoperative cardiac failure."} {"id": "PMID:1265249", "title": "[Pathophysiology and clinic of coronary insufficiency (author's transl)].", "content": "Coronary insufficiency is defined. Some specialities of coronary circulation and aspects of their regulation are discussed. Physical mechanisms such as arteriovenous pressure gradient, vascular and extravascular components of the coronary resistance, the influence of rhythm change on the contraction-conditions of the myocardium, as well as the pulse-rate are differentiated from biological regulation mechanism, such as metabolic, nervous and hormone influences. The typical distrubance of this regulation in the coronary insufficiency is emphasized including impaired left ventricular function. In the second part, the clinic or coronary insufficiency deducted from the anatomical-pathological lesions as well as their pathophysical relations is dealt with, for instance manifestation of angina pectoris and myocardial infarct. The indications and contra-indications for selective coronary angiography are described.", "contents": "[Pathophysiology and clinic of coronary insufficiency (author's transl)]. Coronary insufficiency is defined. Some specialities of coronary circulation and aspects of their regulation are discussed. Physical mechanisms such as arteriovenous pressure gradient, vascular and extravascular components of the coronary resistance, the influence of rhythm change on the contraction-conditions of the myocardium, as well as the pulse-rate are differentiated from biological regulation mechanism, such as metabolic, nervous and hormone influences. The typical distrubance of this regulation in the coronary insufficiency is emphasized including impaired left ventricular function. In the second part, the clinic or coronary insufficiency deducted from the anatomical-pathological lesions as well as their pathophysical relations is dealt with, for instance manifestation of angina pectoris and myocardial infarct. The indications and contra-indications for selective coronary angiography are described."} {"id": "PMID:1265250", "title": "[Significance of roentgenologic and nuclear medicine methods in diagnosis and operative indications of coronary artery disease (author's transl)].", "content": "Significance and technique of roentgenologic and nuclear medicine methods for evaluation of coronary artery disease and myocardial perfusion are presented. Some routinely used methods in nuclear medicine are briefly discussed concerning the evaluation of left ventricular function.", "contents": "[Significance of roentgenologic and nuclear medicine methods in diagnosis and operative indications of coronary artery disease (author's transl)]. Significance and technique of roentgenologic and nuclear medicine methods for evaluation of coronary artery disease and myocardial perfusion are presented. Some routinely used methods in nuclear medicine are briefly discussed concerning the evaluation of left ventricular function."} {"id": "PMID:1265243", "title": "An innovation in testing.", "content": "The testing method presented here is just one of a variety of \"games\" that are being utilized in teaching at all levels. It helps to make testing fun, capitalizes on the student's natural tendency to fool around, and teaches something in the process.", "contents": "An innovation in testing. The testing method presented here is just one of a variety of \"games\" that are being utilized in teaching at all levels. It helps to make testing fun, capitalizes on the student's natural tendency to fool around, and teaches something in the process."} {"id": "PMID:1265245", "title": "A rationale for behavioral objectives in the teaching of radiologic technology.", "content": "Even after fifteen years of use, behavioral objectives are still the subject of controversy. In radiologic technology programs their use is relatively new and not too well understood by some. This statement, therefore, briefly emphasizes why it is important to the student and teacher alike to identify what the student will be expected to achieve and how the degree of his achievement will be assessed.", "contents": "A rationale for behavioral objectives in the teaching of radiologic technology. Even after fifteen years of use, behavioral objectives are still the subject of controversy. In radiologic technology programs their use is relatively new and not too well understood by some. This statement, therefore, briefly emphasizes why it is important to the student and teacher alike to identify what the student will be expected to achieve and how the degree of his achievement will be assessed."} {"id": "PMID:1265251", "title": "Intrathoracic stomach: when does it obstruct?", "content": "Large esophageal and paraesophageal gastric herniations may occasionally produce gastric obstruction and strangulation. Seven cases of gastric intrathoracic herniation of varying degree, including 2 with obstruction, are presented with diagrams of the anatomy in each case. The cases with obstruction are discussed in relation to existing theories of the mechanism of obstruction: (a) tightness of the hernial ring; (b) acute volvulis of the herniated stomach; and (c) subdiaphragmatic redescent of the fundus with fundic distension and crowding of the hernial orifice. It is concluded that the last mechanism is the most common, but that a combination of mechanisms produces the obstruction in some cases.", "contents": "Intrathoracic stomach: when does it obstruct? Large esophageal and paraesophageal gastric herniations may occasionally produce gastric obstruction and strangulation. Seven cases of gastric intrathoracic herniation of varying degree, including 2 with obstruction, are presented with diagrams of the anatomy in each case. The cases with obstruction are discussed in relation to existing theories of the mechanism of obstruction: (a) tightness of the hernial ring; (b) acute volvulis of the herniated stomach; and (c) subdiaphragmatic redescent of the fundus with fundic distension and crowding of the hernial orifice. It is concluded that the last mechanism is the most common, but that a combination of mechanisms produces the obstruction in some cases."} {"id": "PMID:1265242", "title": "System designed to improve communication process between patient and technologist.", "content": "With the use of more specialized equipment in our radiology departments, we are able to examine more patients with greater efficiency. However, our role as radiologic technologists is only partially fulfilled if our concern over the number of patients and the functional aspects of the equipment restricts us from adequately communicating with the patient during the radiographic examination.", "contents": "System designed to improve communication process between patient and technologist. With the use of more specialized equipment in our radiology departments, we are able to examine more patients with greater efficiency. However, our role as radiologic technologists is only partially fulfilled if our concern over the number of patients and the functional aspects of the equipment restricts us from adequately communicating with the patient during the radiographic examination."} {"id": "PMID:1265246", "title": "Radiation therapy technologist survey: state of Michigan.", "content": "A survey of institutions in Michigan utilizing megavoltage equipment demonstrated a shortage of certified radiation therapy technologists. The low number of such personnel who can be trained in the available approved programs in the state is barely sufficient to maintain the present level. Projections show a continued shortage and a need for more approved radiation therapy technology training programs.", "contents": "Radiation therapy technologist survey: state of Michigan. A survey of institutions in Michigan utilizing megavoltage equipment demonstrated a shortage of certified radiation therapy technologists. The low number of such personnel who can be trained in the available approved programs in the state is barely sufficient to maintain the present level. Projections show a continued shortage and a need for more approved radiation therapy technology training programs."} {"id": "PMID:1265252", "title": "The left lateral view in the plain-film assessment of abdominal distension.", "content": "Since the left lateral position facilitates the entry of air into the rectosigmoid, it has been employed in the plain-film evaluation of patients with abdominal distension. The value of this view is illustrated by examples of patients with (a) colonic ileus due to imipramine hydrochloride (Tofranil) or chlorpromazine, (b) partial mechanical obstruction due to diverticulitis, (c) involvement of the rectum by Hirschsprung's disease, and (d) sequential evaluation of a patient with clindamycin colitis. This simple maneuver is recommended for (a) evaluation of patients with plain-film evidence of low colonic obstruction, (b) problems of differential diagnosis between bowel obstruction and ileus, and (c) evaluation of patients with conditions affecting the rectosigmoid.", "contents": "The left lateral view in the plain-film assessment of abdominal distension. Since the left lateral position facilitates the entry of air into the rectosigmoid, it has been employed in the plain-film evaluation of patients with abdominal distension. The value of this view is illustrated by examples of patients with (a) colonic ileus due to imipramine hydrochloride (Tofranil) or chlorpromazine, (b) partial mechanical obstruction due to diverticulitis, (c) involvement of the rectum by Hirschsprung's disease, and (d) sequential evaluation of a patient with clindamycin colitis. This simple maneuver is recommended for (a) evaluation of patients with plain-film evidence of low colonic obstruction, (b) problems of differential diagnosis between bowel obstruction and ileus, and (c) evaluation of patients with conditions affecting the rectosigmoid."} {"id": "PMID:1265253", "title": "\"Blind\" evaluation of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic carcinoma: the \"double duct\" and other signs.", "content": "A \"blind\" review of 40 \"look-alike\" ERCP examinations was conducted to determine if pancreatic carcinoma could be diagnosed by ERCP findings alone, and if there were specific findings which occurred only in carcinoma. All 11 cases of carcinoma involving the pancreas were diagnosed correctly, with no false positives or negatives. Irregular (nodular or rat-tailed) pancreatic duct encasement or obstruction occurred exclusively in carcinoma. When the adjacent common bile duct was similarly involved (Double Duct Sign), the diagnostic certainty increased. The results suggest that ERCP is an accurate and reliable method for diagnosing pancreatic carcinoma.", "contents": "\"Blind\" evaluation of endoscopic retrograde cholangiopancreatography (ERCP) in the diagnosis of pancreatic carcinoma: the \"double duct\" and other signs. A \"blind\" review of 40 \"look-alike\" ERCP examinations was conducted to determine if pancreatic carcinoma could be diagnosed by ERCP findings alone, and if there were specific findings which occurred only in carcinoma. All 11 cases of carcinoma involving the pancreas were diagnosed correctly, with no false positives or negatives. Irregular (nodular or rat-tailed) pancreatic duct encasement or obstruction occurred exclusively in carcinoma. When the adjacent common bile duct was similarly involved (Double Duct Sign), the diagnostic certainty increased. The results suggest that ERCP is an accurate and reliable method for diagnosing pancreatic carcinoma."} {"id": "PMID:1265254", "title": "Priscoline-augmented hepatic angiography.", "content": "Tolazoline hydrochloride (Priscoline) is a useful adjunct to hepatic angiography in the evaluation of space-occupying lesions. It was of definite value in 8 of 26 studies, either in facillitating the diagnosis or in evaluating the extent of disease. The mechanism of enhanced visualization is presumably related to its vasodilatory effect on the small blood vessels of the liver. Priscoline deserves further evaluation in the following situations: (a) a negative hepatic angiogram in the face of positive clinical findings or radionuclide images; (b) suspicious but not definitive findings on conventional hepatic angiography; and (c) assessment of the full extent of disease.", "contents": "Priscoline-augmented hepatic angiography. Tolazoline hydrochloride (Priscoline) is a useful adjunct to hepatic angiography in the evaluation of space-occupying lesions. It was of definite value in 8 of 26 studies, either in facillitating the diagnosis or in evaluating the extent of disease. The mechanism of enhanced visualization is presumably related to its vasodilatory effect on the small blood vessels of the liver. Priscoline deserves further evaluation in the following situations: (a) a negative hepatic angiogram in the face of positive clinical findings or radionuclide images; (b) suspicious but not definitive findings on conventional hepatic angiography; and (c) assessment of the full extent of disease."} {"id": "PMID:1265244", "title": "45-degree central ray angulation for improved lumbosacral myelography.", "content": "Forty-five-degree central ray angulation was utilized during radiography of the lumbosacral region at the time of myelography in 70 patients. The resulting radiographic image allowed for improved assessment of nerve root detail in the region of the fifth lumbar vertebral body and below.", "contents": "45-degree central ray angulation for improved lumbosacral myelography. Forty-five-degree central ray angulation was utilized during radiography of the lumbosacral region at the time of myelography in 70 patients. The resulting radiographic image allowed for improved assessment of nerve root detail in the region of the fifth lumbar vertebral body and below."} {"id": "PMID:1265255", "title": "Spurious complete obstruction of the inferior vena cava in an adult as a result of the Valsalva maneuver.", "content": "The authors describe a case of spurious complete obstruction of the inferior vena cava in a 60-year-old man, which proved to be the result of a Valsalva maneuver. It is recommended that if an apparent abnormality is noted on supine inferior vena cavography, the position of the patient be changed and additional films obtained in different projections without the Valsalva maneuver.", "contents": "Spurious complete obstruction of the inferior vena cava in an adult as a result of the Valsalva maneuver. The authors describe a case of spurious complete obstruction of the inferior vena cava in a 60-year-old man, which proved to be the result of a Valsalva maneuver. It is recommended that if an apparent abnormality is noted on supine inferior vena cavography, the position of the patient be changed and additional films obtained in different projections without the Valsalva maneuver."} {"id": "PMID:1265256", "title": "Radiographic aspects of permanent cardiac pacemakers.", "content": "Radiographic findings in patients with permanent cardiac pacemakers are described, and recent advances in pulse generator and lead design are presented. Emphasis is placed on those findings which are related to (a) complications of cardiac pacing, (b) radiographic configurations of new energy sources and lead/electrode systems, and (c) a new system of pulse generator identification.", "contents": "Radiographic aspects of permanent cardiac pacemakers. Radiographic findings in patients with permanent cardiac pacemakers are described, and recent advances in pulse generator and lead design are presented. Emphasis is placed on those findings which are related to (a) complications of cardiac pacing, (b) radiographic configurations of new energy sources and lead/electrode systems, and (c) a new system of pulse generator identification."} {"id": "PMID:1265257", "title": "\"Dimple sign\" produced by a benign cystic renal mass.", "content": "A benign cystic renal lesion causing a mass effect in the kidney is reported. The mass was associated with a \"double dimple sign,\" heretofore reported only in malignant renal tumors.", "contents": "\"Dimple sign\" produced by a benign cystic renal mass. A benign cystic renal lesion causing a mass effect in the kidney is reported. The mass was associated with a \"double dimple sign,\" heretofore reported only in malignant renal tumors."} {"id": "PMID:1265258", "title": "Clinical and radiographic abnormalities in ankylosing spondylitis: a comparison of men and women.", "content": "A clinical and radiographic study of 98 patients with definite ankylosing spondylitis (Rome criteria) was undertaken to evaluate differences in men and women with the disease. Clinical manifestations which were atypical in the 18 female patients when compared to those of the men included older age of disease onset, higher incidence of initial and subsequent peripheral joint disease, more common cervical spine symptomatology, and milder disease course. Radiographic differences in the women included a high incidence of cervical spine abnormalities, a combination of cervical spine and sacroiliac joint alterations with a normal intervening thoracic and lumbar segment, and frequent and severe osteitis pubis.", "contents": "Clinical and radiographic abnormalities in ankylosing spondylitis: a comparison of men and women. A clinical and radiographic study of 98 patients with definite ankylosing spondylitis (Rome criteria) was undertaken to evaluate differences in men and women with the disease. Clinical manifestations which were atypical in the 18 female patients when compared to those of the men included older age of disease onset, higher incidence of initial and subsequent peripheral joint disease, more common cervical spine symptomatology, and milder disease course. Radiographic differences in the women included a high incidence of cervical spine abnormalities, a combination of cervical spine and sacroiliac joint alterations with a normal intervening thoracic and lumbar segment, and frequent and severe osteitis pubis."} {"id": "PMID:1265259", "title": "The flared mandible sign of the flail mandible.", "content": "A useful radiographic finding is described for the diagnosis of a flail mandible. The flail mandible removes forward support for the tongue, which may result in airway obstruction. Immediate radiographic diagnosis allows quick surgical correction of the fractured mandible and relief of the obstruction, decreasing the time during which an endotracheal or tracheostomy tube is needed to keep the airway open.", "contents": "The flared mandible sign of the flail mandible. A useful radiographic finding is described for the diagnosis of a flail mandible. The flail mandible removes forward support for the tongue, which may result in airway obstruction. Immediate radiographic diagnosis allows quick surgical correction of the fractured mandible and relief of the obstruction, decreasing the time during which an endotracheal or tracheostomy tube is needed to keep the airway open."} {"id": "PMID:1265260", "title": "Angiography in the diagnosis and therapy of frostbite.", "content": "Five patients with frostbite injury were studied by selective angiography and treated by selective intra-arterial application of reserpine with follow-up angiography two days later. Control angiograms showed various degrees of vascular spasm as well as organic stenosis and occlusion. Intra-arterial reserpine produced dramatic subsiding of vasospasm, as evidenced by angiography and relief of clinical symptoms. Complete healing without tissue loss occurred in 4 patients. Amputation was necessary in one case, due at least in part to pre-existing peripheral atherosclerotic disease. Selective angiography was found to contribute significantly to both the diagnosis and therapy of frostbite injury.", "contents": "Angiography in the diagnosis and therapy of frostbite. Five patients with frostbite injury were studied by selective angiography and treated by selective intra-arterial application of reserpine with follow-up angiography two days later. Control angiograms showed various degrees of vascular spasm as well as organic stenosis and occlusion. Intra-arterial reserpine produced dramatic subsiding of vasospasm, as evidenced by angiography and relief of clinical symptoms. Complete healing without tissue loss occurred in 4 patients. Amputation was necessary in one case, due at least in part to pre-existing peripheral atherosclerotic disease. Selective angiography was found to contribute significantly to both the diagnosis and therapy of frostbite injury."} {"id": "PMID:1265261", "title": "Lung carcinoma superimposed on pulmonary tuberculosis.", "content": "Review of patients with active pulmonary tuberculosis over a three-year period showed an increased incidence of bronchogenic carcinoma (5%). There had been considerable delay in establishing diagnosis of coexistent carcinoma which was attributed to finding of acid-fast bacilli and relative ease of ascribing all findings to that cause. Suspicious roentgen signs are reviewed and the importance of sputum cytology is also stressed.", "contents": "Lung carcinoma superimposed on pulmonary tuberculosis. Review of patients with active pulmonary tuberculosis over a three-year period showed an increased incidence of bronchogenic carcinoma (5%). There had been considerable delay in establishing diagnosis of coexistent carcinoma which was attributed to finding of acid-fast bacilli and relative ease of ascribing all findings to that cause. Suspicious roentgen signs are reviewed and the importance of sputum cytology is also stressed."} {"id": "PMID:1265262", "title": "Protracted yet variable major pulmonary artery compression in sarcoidosis.", "content": "A case of thoracic sarcoidosis showing diffuse mediastinal lymphadenopathy was followed for a 6-month period with serial chest radiographs, perfusion lung scans, and pulmonary angiograms. Significant extrinsic pressure upon major pulmonary arteries from large lymph nodes of sarcoidosis was seen to cause marked restriction in pulmonary parenchymal perfusion on both scanning and angiography.", "contents": "Protracted yet variable major pulmonary artery compression in sarcoidosis. A case of thoracic sarcoidosis showing diffuse mediastinal lymphadenopathy was followed for a 6-month period with serial chest radiographs, perfusion lung scans, and pulmonary angiograms. Significant extrinsic pressure upon major pulmonary arteries from large lymph nodes of sarcoidosis was seen to cause marked restriction in pulmonary parenchymal perfusion on both scanning and angiography."} {"id": "PMID:1265263", "title": "Early clinical experience with motionless whole-body computed tomography.", "content": "A new computed tomographic body scanner, capable of completing a scan in 18 sec., produces dramatically clearer and more precise pictures of the abdomen and thorax than heretofore possible. Other technical improvements result in increased clarity in areas of the body not affected by motion, including the brain. Potential clinical uses are illustrated.", "contents": "Early clinical experience with motionless whole-body computed tomography. A new computed tomographic body scanner, capable of completing a scan in 18 sec., produces dramatically clearer and more precise pictures of the abdomen and thorax than heretofore possible. Other technical improvements result in increased clarity in areas of the body not affected by motion, including the brain. Potential clinical uses are illustrated."} {"id": "PMID:1265265", "title": "The normal anterior inferior cerebellar artery. Anatomic-radiographic correlation with emphasis on the lateral projection.", "content": "Previous descriptions of the course and anatomic relationships of the anterior inferior cerebellar artery (AICA), as visualized in the lateral projection, have not been found by the authors. Dissection and radiography of 32 injected human cerebella show that AICA and its major branches define the position of the pontomedullary sulcus; supra-olivary fossette; 5th-11th cranial nerves; brachium pontis; flocculus; great horizontal fissure; posterolateral fissure; superior semilunar lobule; inferior semilunar lobule; biventral lobule; foramen of Luschka; and the choroid plexus of the lateral recess of the 4th ventricle. With magnification and high-quality subtraction, AICA and its associated structures may be identified in the lateral projection in the large majority of patients.", "contents": "The normal anterior inferior cerebellar artery. Anatomic-radiographic correlation with emphasis on the lateral projection. Previous descriptions of the course and anatomic relationships of the anterior inferior cerebellar artery (AICA), as visualized in the lateral projection, have not been found by the authors. Dissection and radiography of 32 injected human cerebella show that AICA and its major branches define the position of the pontomedullary sulcus; supra-olivary fossette; 5th-11th cranial nerves; brachium pontis; flocculus; great horizontal fissure; posterolateral fissure; superior semilunar lobule; inferior semilunar lobule; biventral lobule; foramen of Luschka; and the choroid plexus of the lateral recess of the 4th ventricle. With magnification and high-quality subtraction, AICA and its associated structures may be identified in the lateral projection in the large majority of patients."} {"id": "PMID:1265266", "title": "Calvarial and vertebral sarcoidosis. Case report and review of the literature.", "content": "A case of associated calvarial and cervical spine lesions in sarcoidosis is reported. The radiographic findings are discussed and the literature is reviewed.", "contents": "Calvarial and vertebral sarcoidosis. Case report and review of the literature. A case of associated calvarial and cervical spine lesions in sarcoidosis is reported. The radiographic findings are discussed and the literature is reviewed."} {"id": "PMID:1265267", "title": "Familial \"doughnut\" lesions of the skull. A benign, hereditary dysplasia.", "content": "Multiple calvarial doughnut lesions present a dramatic roentgenographic picture. The scant literature indicates that they are benign, asymptomatic, and of obscure etiology. Three additional examples of this rare entity have been identified all in the same family and are presented. The implication of a familial relationship with regard to develpmental pathogenesis is discussed. Histology is nonspecific but is felt to be consistent with hyperostosis.", "contents": "Familial \"doughnut\" lesions of the skull. A benign, hereditary dysplasia. Multiple calvarial doughnut lesions present a dramatic roentgenographic picture. The scant literature indicates that they are benign, asymptomatic, and of obscure etiology. Three additional examples of this rare entity have been identified all in the same family and are presented. The implication of a familial relationship with regard to develpmental pathogenesis is discussed. Histology is nonspecific but is felt to be consistent with hyperostosis."} {"id": "PMID:1265269", "title": "Histological changes in the central nervous system following intraventricular administration of oil-soluble contrast media. An experimental study in the rat.", "content": "Following injections of iodophendylate (Pantopaque) in adult rats, the contrast medium was shown to be refrained in the dilated cerebral ventricles for at least 180 days. Histological examination revealed macrophages containing phagocytosed lipid on the ependymal lining of the ventricles, but there was no leukocytic reaction to retained or encysted contrast material. The macrophages were considered to be involved in the removal of iodophendylate. The irritative reaction in the normal central nervous system was limited, as opposed to the severe reactions previously reported in animals with inflammation of the brain and meninges.", "contents": "Histological changes in the central nervous system following intraventricular administration of oil-soluble contrast media. An experimental study in the rat. Following injections of iodophendylate (Pantopaque) in adult rats, the contrast medium was shown to be refrained in the dilated cerebral ventricles for at least 180 days. Histological examination revealed macrophages containing phagocytosed lipid on the ependymal lining of the ventricles, but there was no leukocytic reaction to retained or encysted contrast material. The macrophages were considered to be involved in the removal of iodophendylate. The irritative reaction in the normal central nervous system was limited, as opposed to the severe reactions previously reported in animals with inflammation of the brain and meninges."} {"id": "PMID:1265270", "title": "Progressive multifocal leukoencephalopathy.", "content": "The radionuclide, radiographic and pathologic findings in a patient with progressive multifocal leukoencephalopathy were correlated. Radionuclide imaging demonstrated the largest two of the many lesions observed at pathology. On repeated studies, one of the lesions developed a \"doughnut\" sign due to central necrosis. Cerebral angiography disclosed only one lesion which was initially suggestive of tumor encasement, but four weeks later, this deteriorated into an avascular zone. There were no characteristic features of the lesions demonstrated by radionuclide imaging and cerebral angiography that could be specifically attributed to progressive multifocal leukoencephalopathy.", "contents": "Progressive multifocal leukoencephalopathy. The radionuclide, radiographic and pathologic findings in a patient with progressive multifocal leukoencephalopathy were correlated. Radionuclide imaging demonstrated the largest two of the many lesions observed at pathology. On repeated studies, one of the lesions developed a \"doughnut\" sign due to central necrosis. Cerebral angiography disclosed only one lesion which was initially suggestive of tumor encasement, but four weeks later, this deteriorated into an avascular zone. There were no characteristic features of the lesions demonstrated by radionuclide imaging and cerebral angiography that could be specifically attributed to progressive multifocal leukoencephalopathy."} {"id": "PMID:1265271", "title": "The radiographic features of mannosidosis.", "content": "Skeletal changes seen in 12 patients with mannosidosis included thickened calvaria, ovoid configuration, flattening and hook-shaped deformity of the vertebral bodies, hypoplasia of the inferior portions of the ilia, and mild expansion of the short tubular bones of the hands. The pattern of skeletal changes is that of mild to moderate dysostosis multiplex with considerable intrafamilial variation. The skeletal abnormalities may decrease with age. Correlation of the skeletal abnormalities with clinical and biochemical findings is necessary for a specific diagnosis.", "contents": "The radiographic features of mannosidosis. Skeletal changes seen in 12 patients with mannosidosis included thickened calvaria, ovoid configuration, flattening and hook-shaped deformity of the vertebral bodies, hypoplasia of the inferior portions of the ilia, and mild expansion of the short tubular bones of the hands. The pattern of skeletal changes is that of mild to moderate dysostosis multiplex with considerable intrafamilial variation. The skeletal abnormalities may decrease with age. Correlation of the skeletal abnormalities with clinical and biochemical findings is necessary for a specific diagnosis."} {"id": "PMID:1265272", "title": "Postoperative chylothorax in children with congenital heart disease. Clinical and roentgenographic features.", "content": "The clinical and roentgenographic findings in 11 children were reviewed following development of a chylothorax after surgery for the management of congenital heart disease. The operative site in most cases was in proximity to the aortic isthmus. The pleural effusion was delayed in onset, reaccumulated rapidly after initial thoracentesis, and frequently recurred after apparent resolution. In most patients, widening of the mediastinum was noted prior to the appearance of the pleural effusion. Anatomical features of the thoracic duct and pathophysiologic concepts operative in chylothorax are reviewed and related to the clinical and roentgenographic characteristics of this entity.", "contents": "Postoperative chylothorax in children with congenital heart disease. Clinical and roentgenographic features. The clinical and roentgenographic findings in 11 children were reviewed following development of a chylothorax after surgery for the management of congenital heart disease. The operative site in most cases was in proximity to the aortic isthmus. The pleural effusion was delayed in onset, reaccumulated rapidly after initial thoracentesis, and frequently recurred after apparent resolution. In most patients, widening of the mediastinum was noted prior to the appearance of the pleural effusion. Anatomical features of the thoracic duct and pathophysiologic concepts operative in chylothorax are reviewed and related to the clinical and roentgenographic characteristics of this entity."} {"id": "PMID:1265273", "title": "Gray scale ultrasound imaging. The anatomy and pathology of the liver.", "content": "Gray scale ultrasound imaging circumvents some of the limitations of other diagnostic tools. The authors have extended this technique to the investigation of hepatobiliary disease. The details of their equipment are described and their results in relation to various parameters of the disease are discussed. A major feature of the gray scale technique is the enhanced signal-noise ratio, which allows low-level echoes to be displayed.", "contents": "Gray scale ultrasound imaging. The anatomy and pathology of the liver. Gray scale ultrasound imaging circumvents some of the limitations of other diagnostic tools. The authors have extended this technique to the investigation of hepatobiliary disease. The details of their equipment are described and their results in relation to various parameters of the disease are discussed. A major feature of the gray scale technique is the enhanced signal-noise ratio, which allows low-level echoes to be displayed."} {"id": "PMID:1265274", "title": "Ultrasonically-guided percutaneous nephrostomy. Report of 24 cases.", "content": "Ultrasonically-guided percutaneous nephrostomy using the Seldinger technique was attempted on 24 kidneys in 19 patients with obstructive hydronephrosis. Seventeen of the procedures were successful, 4 failed, and in 3 the catheter slipped out of the renal pelvis 1-48 hours after insertion. The procedure is simple and independent of renal function. Postrenal uremia can be relieved, infected hydronephrosis drained prior to elective surgery, and urinary parameters assessed. Injection of contrast material can define pathological anatomy in those cases where excretory urography and retrograde pyelography are unsatisfactory. No significant complications were encountered.", "contents": "Ultrasonically-guided percutaneous nephrostomy. Report of 24 cases. Ultrasonically-guided percutaneous nephrostomy using the Seldinger technique was attempted on 24 kidneys in 19 patients with obstructive hydronephrosis. Seventeen of the procedures were successful, 4 failed, and in 3 the catheter slipped out of the renal pelvis 1-48 hours after insertion. The procedure is simple and independent of renal function. Postrenal uremia can be relieved, infected hydronephrosis drained prior to elective surgery, and urinary parameters assessed. Injection of contrast material can define pathological anatomy in those cases where excretory urography and retrograde pyelography are unsatisfactory. No significant complications were encountered."} {"id": "PMID:1265275", "title": "Radiographic imaging using an effective rotationally symmetrical focal spot.", "content": "A mathematical model is presented for predicting the effect of rotation on certain types os asymmetric focal spot intensity distributions. Experimental rotational techniques are used to obtain rotationally symmetric, gaussian-like focal spot distributions from existing asymmetric distributions. Radiographic examples are shown which illustrate the resulting imaging effect of such rotationally symmetric focal spots compared to existing focal spots. In particular, images of resolution test patterns and simulated blood vessels are used to examine some of the radiographic consequences (contrast transfer and spurious imaging) of the use of differing types of focal spot intensity distributions, and to question the utility of single number characterizations of asymmetric focal spots.", "contents": "Radiographic imaging using an effective rotationally symmetrical focal spot. A mathematical model is presented for predicting the effect of rotation on certain types os asymmetric focal spot intensity distributions. Experimental rotational techniques are used to obtain rotationally symmetric, gaussian-like focal spot distributions from existing asymmetric distributions. Radiographic examples are shown which illustrate the resulting imaging effect of such rotationally symmetric focal spots compared to existing focal spots. In particular, images of resolution test patterns and simulated blood vessels are used to examine some of the radiographic consequences (contrast transfer and spurious imaging) of the use of differing types of focal spot intensity distributions, and to question the utility of single number characterizations of asymmetric focal spots."} {"id": "PMID:1265276", "title": "The production of apparent image bifurcation.", "content": "It is well known that x-ray focal spots with split-intensity distributions can produce radiographs exhibiting image bifurcations. The authors observed such bifurcations in optical analogue images which were produced with both split- and uniform-intesity focal spots. The bifurcations observed with the split focal spot were real, while those observed with the uniform focal spot were not observed in photometer scans of the object. The authors explain these bifurcations by a consideration of the response function of the eye.", "contents": "The production of apparent image bifurcation. It is well known that x-ray focal spots with split-intensity distributions can produce radiographs exhibiting image bifurcations. The authors observed such bifurcations in optical analogue images which were produced with both split- and uniform-intesity focal spots. The bifurcations observed with the split focal spot were real, while those observed with the uniform focal spot were not observed in photometer scans of the object. The authors explain these bifurcations by a consideration of the response function of the eye."} {"id": "PMID:1265277", "title": "Exposure of radiologists to scattered radiation during radiodiagnostic examinations.", "content": "The exposure to scattered radiation was measured on both hands, the forehead and gonads of six radiologists by means of thermoluminescent dosimeters in two fluoroscopy rooms. Exposure of the forehead was found not to exceed approximately 1% of the maximum permissible exposure (MPD) (3% pursuant to NCRP (recommendations). During examinations of the colon, the exposure of the right hand proved to be significantly higher compared to the left. There was only slight exposure to the gonads as measured behind the apron.", "contents": "Exposure of radiologists to scattered radiation during radiodiagnostic examinations. The exposure to scattered radiation was measured on both hands, the forehead and gonads of six radiologists by means of thermoluminescent dosimeters in two fluoroscopy rooms. Exposure of the forehead was found not to exceed approximately 1% of the maximum permissible exposure (MPD) (3% pursuant to NCRP (recommendations). During examinations of the colon, the exposure of the right hand proved to be significantly higher compared to the left. There was only slight exposure to the gonads as measured behind the apron."} {"id": "PMID:1265278", "title": "A fast neutron source for cultured cell irradiation.", "content": "Because of recent interest in the use of neutrons for radiotherapy, there has been an increased interest in the radiology of neutrons. In this irradiated cell study, a 1.3 MeV accelerator produced beam currents over 100 muA on the water-cooled 3-mm thick beryllium disk target. The monolayer of irradiated cells was neutron-shielded by about 700 kg of paraffin. The neutron energy spectrum for the 9Be(d,n)10B reaction was obtained, with an average neutron energy calculated to be between 3.3 and 3.5 MeV, and an average linear energy transfer calculated at more than 30 keV/micron.", "contents": "A fast neutron source for cultured cell irradiation. Because of recent interest in the use of neutrons for radiotherapy, there has been an increased interest in the radiology of neutrons. In this irradiated cell study, a 1.3 MeV accelerator produced beam currents over 100 muA on the water-cooled 3-mm thick beryllium disk target. The monolayer of irradiated cells was neutron-shielded by about 700 kg of paraffin. The neutron energy spectrum for the 9Be(d,n)10B reaction was obtained, with an average neutron energy calculated to be between 3.3 and 3.5 MeV, and an average linear energy transfer calculated at more than 30 keV/micron."} {"id": "PMID:1265279", "title": "Survival of mouse L-929 cells following neutron irradiation.", "content": "Mouse L-929 cells were exposed in a monolayer to x rays and to a 3.5 MeV neutron beam for comparison of damage effects. Single dose experiments showed a radiobiological effectiveness of 1.5 for neutrons when compared to x rays. Both single and paired dose experiments indicated that the cells were unable to repair neutron-induced damage. Dinitrophenol was found to increase the survival of those cells irradiated with neutrons.", "contents": "Survival of mouse L-929 cells following neutron irradiation. Mouse L-929 cells were exposed in a monolayer to x rays and to a 3.5 MeV neutron beam for comparison of damage effects. Single dose experiments showed a radiobiological effectiveness of 1.5 for neutrons when compared to x rays. Both single and paired dose experiments indicated that the cells were unable to repair neutron-induced damage. Dinitrophenol was found to increase the survival of those cells irradiated with neutrons."} {"id": "PMID:1265280", "title": "Evaluation of times of maximal involvement for early skin reactions following x irradiation combined with hyperthermic treatment.", "content": "Times of maximal involvement in mouse skin were determined for reactions produced by graded doses of x irradiation combined with hyperthermic treatment at 37.5, 41, 42, 42.5 and 43 degrees C for one hour. The times of maximal involvement in each case were found to be independent of thermal treatment. These data provide indirect evidence that hyperthermic treatment does not modify the kinetics of epithelial proliferation or alter the progress of early radiation reactions.", "contents": "Evaluation of times of maximal involvement for early skin reactions following x irradiation combined with hyperthermic treatment. Times of maximal involvement in mouse skin were determined for reactions produced by graded doses of x irradiation combined with hyperthermic treatment at 37.5, 41, 42, 42.5 and 43 degrees C for one hour. The times of maximal involvement in each case were found to be independent of thermal treatment. These data provide indirect evidence that hyperthermic treatment does not modify the kinetics of epithelial proliferation or alter the progress of early radiation reactions."} {"id": "PMID:1265283", "title": "A developer solution for tank processing of x-ray film under ambient, tropical conditions.", "content": "A modification of a proprietary 90-sec. x-ray-film developer which permits its use as a hand-tank developer at ambient temperatures between 21.6 degrees-30.6 degrees C (80 degrees-100 degrees F) is described. This processing technique is useful in tropical countries where the control of developer temperature is particularly difficult.", "contents": "A developer solution for tank processing of x-ray film under ambient, tropical conditions. A modification of a proprietary 90-sec. x-ray-film developer which permits its use as a hand-tank developer at ambient temperatures between 21.6 degrees-30.6 degrees C (80 degrees-100 degrees F) is described. This processing technique is useful in tropical countries where the control of developer temperature is particularly difficult."} {"id": "PMID:1265284", "title": "A simple myelographic maneuver for the detection of mass lesions at the foramen magnum.", "content": "Popular belief and teaching has emphasized the necessity for supine myelography to avoid missing lesions on the dorsal aspect of the foramen magnum; however, this required not only additional time but also considerable discomfort for the patient. A simple maneuver added to the prone myelogram, requiring little additional time and no discomfort, virtually assures the detection of lesions at or near the foramen magnum. This technique has been used in 40 patients suspected of having either a demyelinating process or a mass lesion involving the high cervical cord. Eight Chiari malformations and 1 meningioma were demonstrated.", "contents": "A simple myelographic maneuver for the detection of mass lesions at the foramen magnum. Popular belief and teaching has emphasized the necessity for supine myelography to avoid missing lesions on the dorsal aspect of the foramen magnum; however, this required not only additional time but also considerable discomfort for the patient. A simple maneuver added to the prone myelogram, requiring little additional time and no discomfort, virtually assures the detection of lesions at or near the foramen magnum. This technique has been used in 40 patients suspected of having either a demyelinating process or a mass lesion involving the high cervical cord. Eight Chiari malformations and 1 meningioma were demonstrated."} {"id": "PMID:1265286", "title": "The who, why and how of radiology teaching files.", "content": "A variety of teaching files in diagnostic radiology is needed to serve a broad spectrum of purposes and students. A method of acquiring a simplified teaching file to be used for and by medical students, non-radiology house staff, first-year radiology residents and senior staff members is described. The medical student, as a learning experience, acts as the procurer of this file.", "contents": "The who, why and how of radiology teaching files. A variety of teaching files in diagnostic radiology is needed to serve a broad spectrum of purposes and students. A method of acquiring a simplified teaching file to be used for and by medical students, non-radiology house staff, first-year radiology residents and senior staff members is described. The medical student, as a learning experience, acts as the procurer of this file."} {"id": "PMID:1265292", "title": "Release of prostaglandins from healthy and sensitized guinea-pig lung and trachea by histamine.", "content": "The effects of histamine and its antagonists on the release of prostaglandin E and F2alpha (PGE and PGF2alpha) and the 15-keto-13,14-dihydro PGF2alpha/E (metabolites) were examined in minced and whole perfused guinea pig lung. Lung fragments released considerable amounts of prostaglandins into the incubation media with time alone: parenchyma more PGF2alpha than PGE, trachea more PGE than PGF2alpha. The levels of PGF2alpha found in the filtrates of both tissues on per gram basis were about the same, whereas the concentrations of PGE were several fold higher in the media of incubated trachea. In contrast to lung, trachea released only trace amounts of metabolites. These differences in synthesis and turnover are probably of importance for maintenance of the adequate ventilation-perfusion ratios. The process of sensitization caused a significant increase in the outflows of PGF2alpha and metabolites from the lung fragments. The PGE to PGF2alpha ratio was decreased in both parenchymal and tracheal tissues. Increased spontaneous release of prostaglandins was also found in whole perfused sensitized lung. This was consistent with the hypothesis that sensitization with antigen alters the biochemical properties of the organism. Incubation of lung fragments with histamine had only a small additional effect on the liberation of prostaglandins, since the baseline release was high due to the trauma of mincing. However, histamine perfusion of whole lung caused severalfold increase in the outflows of prostaglandins. Pretreatment with pyrilamine (histamine receptor 1 antagonist) decreased the subsequent release of PGF2alpha by histamine. On the other hand, pretreatment with metiamide (histamine receptor 2 antagonist) diminished the subsequent release of PGE. It is suggested that stimulation of histamine receptor 1 is predominantly (but not solely) related to the synthesis of PGF2alpha, and stimulation of the receptor 2 is related to the synthesis of PGE.", "contents": "Release of prostaglandins from healthy and sensitized guinea-pig lung and trachea by histamine. The effects of histamine and its antagonists on the release of prostaglandin E and F2alpha (PGE and PGF2alpha) and the 15-keto-13,14-dihydro PGF2alpha/E (metabolites) were examined in minced and whole perfused guinea pig lung. Lung fragments released considerable amounts of prostaglandins into the incubation media with time alone: parenchyma more PGF2alpha than PGE, trachea more PGE than PGF2alpha. The levels of PGF2alpha found in the filtrates of both tissues on per gram basis were about the same, whereas the concentrations of PGE were several fold higher in the media of incubated trachea. In contrast to lung, trachea released only trace amounts of metabolites. These differences in synthesis and turnover are probably of importance for maintenance of the adequate ventilation-perfusion ratios. The process of sensitization caused a significant increase in the outflows of PGF2alpha and metabolites from the lung fragments. The PGE to PGF2alpha ratio was decreased in both parenchymal and tracheal tissues. Increased spontaneous release of prostaglandins was also found in whole perfused sensitized lung. This was consistent with the hypothesis that sensitization with antigen alters the biochemical properties of the organism. Incubation of lung fragments with histamine had only a small additional effect on the liberation of prostaglandins, since the baseline release was high due to the trauma of mincing. However, histamine perfusion of whole lung caused severalfold increase in the outflows of prostaglandins. Pretreatment with pyrilamine (histamine receptor 1 antagonist) decreased the subsequent release of PGF2alpha by histamine. On the other hand, pretreatment with metiamide (histamine receptor 2 antagonist) diminished the subsequent release of PGE. It is suggested that stimulation of histamine receptor 1 is predominantly (but not solely) related to the synthesis of PGF2alpha, and stimulation of the receptor 2 is related to the synthesis of PGE."} {"id": "PMID:1265293", "title": "Effects of indomethacin and PGE1 on the vasoconstrictor responses of the rabbit ear artery to nerve stimulation.", "content": "Actions of PGE1 and indomethacin on electrically induced vasoconstriction in isolated ear arteries of rabbits were studied. PGE1 (8.5 X 10(-9) M) reduced the vasoconstriction; this inhibition was inversely related to the rate of stimulation. Indomethacin (1.5 X 10(-6) M) potentiated the constrictor responses to nerve stimulation. The degree of this potentiation was also frequency-dependent being greater at low (1 - 2 HZ) than at high (8 - 16 HZ) rate of stimulation. These findings support the view that prostaglandins, in addition to their action on vascular smooth muscle cells, play a functional role in the regulation of tone of the rabbit ear artery by a negative feed-back control of adrenergic neurotransmission.", "contents": "Effects of indomethacin and PGE1 on the vasoconstrictor responses of the rabbit ear artery to nerve stimulation. Actions of PGE1 and indomethacin on electrically induced vasoconstriction in isolated ear arteries of rabbits were studied. PGE1 (8.5 X 10(-9) M) reduced the vasoconstriction; this inhibition was inversely related to the rate of stimulation. Indomethacin (1.5 X 10(-6) M) potentiated the constrictor responses to nerve stimulation. The degree of this potentiation was also frequency-dependent being greater at low (1 - 2 HZ) than at high (8 - 16 HZ) rate of stimulation. These findings support the view that prostaglandins, in addition to their action on vascular smooth muscle cells, play a functional role in the regulation of tone of the rabbit ear artery by a negative feed-back control of adrenergic neurotransmission."} {"id": "PMID:1265294", "title": "Concentration of prostaglandins F in uterine venous plasma of anesthetized mares during the estrous cycle and early pregnancy.", "content": "Prostaglandins F were quantitated by radioimmunoassay in uterine venous plasma of anesthetized mares on day 7 of estrus, days 2, 6, 10, 14 or 18 of diestrus and days 10, 14 or 18 of pregnancy. The PGF concentration was greater (P less than .01) at day 14 of diestrus than at all other days studied. The concentrations at days 10 and 18 of diestrus and at days 10, 14 and 18 of pregnancy were greater (P less than .05) than at day 7 of estrus and days 2 and 6 of diestrus. PGF concentrations at days 10 and 14 were greater (P less than .01) for diestrous than for pregnant mares.", "contents": "Concentration of prostaglandins F in uterine venous plasma of anesthetized mares during the estrous cycle and early pregnancy. Prostaglandins F were quantitated by radioimmunoassay in uterine venous plasma of anesthetized mares on day 7 of estrus, days 2, 6, 10, 14 or 18 of diestrus and days 10, 14 or 18 of pregnancy. The PGF concentration was greater (P less than .01) at day 14 of diestrus than at all other days studied. The concentrations at days 10 and 18 of diestrus and at days 10, 14 and 18 of pregnancy were greater (P less than .05) than at day 7 of estrus and days 2 and 6 of diestrus. PGF concentrations at days 10 and 14 were greater (P less than .01) for diestrous than for pregnant mares."} {"id": "PMID:1265295", "title": "Early termination of pregnancy: a comparative study of intrauterine prostaglandin F2alpha and vacuum aspiration.", "content": "The relative safety and effectiveness of vacuum aspiration and the intrauterine administration of 5 mg PGF2alpha for terminating pregnancies within two weeks of a missed menstrual period were evaluated in a study where subjects were randomly assigned to procedures; 100 patients were aborted with vacuum aspiration and 100 patients were aborted with PGF2alpha. All PGF2alpha-treated patients were premedicated with meperidine, diazepam and atropine. Complications were infrequent with either of the procedures. Vomiting occurred more frequently during the PGF procedure (30.0%) than during the vaccum aspiration procedure (9.0%). The intrauterine instillation of PGF2alpha successfully terminated all pregnancies. One patient continued to be pregnant after the vacuum aspiration procedure. Based on the results of this study both study procedures appeared to be safe and effective for terminating early first trimester pregnancies.", "contents": "Early termination of pregnancy: a comparative study of intrauterine prostaglandin F2alpha and vacuum aspiration. The relative safety and effectiveness of vacuum aspiration and the intrauterine administration of 5 mg PGF2alpha for terminating pregnancies within two weeks of a missed menstrual period were evaluated in a study where subjects were randomly assigned to procedures; 100 patients were aborted with vacuum aspiration and 100 patients were aborted with PGF2alpha. All PGF2alpha-treated patients were premedicated with meperidine, diazepam and atropine. Complications were infrequent with either of the procedures. Vomiting occurred more frequently during the PGF procedure (30.0%) than during the vaccum aspiration procedure (9.0%). The intrauterine instillation of PGF2alpha successfully terminated all pregnancies. One patient continued to be pregnant after the vacuum aspiration procedure. Based on the results of this study both study procedures appeared to be safe and effective for terminating early first trimester pregnancies."} {"id": "PMID:1265296", "title": "Prostaglandin E2 in human gingiva in health and disease and its stimulation by female sex steroids.", "content": "The levels of prostaglandin E2 were measured by means of radioimmunoassay in 12 clinically normal and 24 chronically inflamed human gingival tissue homogenates. The average values were found to be 16 and 285 pmol/gm wet weight of the normal and inflamed samples, respectively. Addition of estradiol-17beta alone or a mixture of estradiol-17beta and progesterone to incubation media containing normal or inflamed gingiva caused a significant increase in the in vitro synthesis of endogenous PGE2. Increased levels of female sex steroids during pregnancy may enhance gingival inflammation.", "contents": "Prostaglandin E2 in human gingiva in health and disease and its stimulation by female sex steroids. The levels of prostaglandin E2 were measured by means of radioimmunoassay in 12 clinically normal and 24 chronically inflamed human gingival tissue homogenates. The average values were found to be 16 and 285 pmol/gm wet weight of the normal and inflamed samples, respectively. Addition of estradiol-17beta alone or a mixture of estradiol-17beta and progesterone to incubation media containing normal or inflamed gingiva caused a significant increase in the in vitro synthesis of endogenous PGE2. Increased levels of female sex steroids during pregnancy may enhance gingival inflammation."} {"id": "PMID:1265297", "title": "A role for prostaglandins in the regulation of the placental blood flows.", "content": "A model is proposed for the regulation of the placental blood flows to the near-term pregnancy. The model has three features. 1) The maternal uterine and fetal placental tissues can synthesize constrictor and dilator prostaglandins. 2) Prostaglandins can cross the placenta. 3) There must exist a prostaglandin which has a vascodilating action in one of the placental circulations and a vasoconstricting action in the other circulation. Evidence is provided to indicate that the sheep, prostaglandin E2 (PGE2) can cross the placenta and has a vasodilating action in the uterine placental circulation and a vasoconstricting action in the umbilical placental circulation. The placenta and the lung are compared and PGE2 is shown to have similar actions in each of these organs.", "contents": "A role for prostaglandins in the regulation of the placental blood flows. A model is proposed for the regulation of the placental blood flows to the near-term pregnancy. The model has three features. 1) The maternal uterine and fetal placental tissues can synthesize constrictor and dilator prostaglandins. 2) Prostaglandins can cross the placenta. 3) There must exist a prostaglandin which has a vascodilating action in one of the placental circulations and a vasoconstricting action in the other circulation. Evidence is provided to indicate that the sheep, prostaglandin E2 (PGE2) can cross the placenta and has a vasodilating action in the uterine placental circulation and a vasoconstricting action in the umbilical placental circulation. The placenta and the lung are compared and PGE2 is shown to have similar actions in each of these organs."} {"id": "PMID:1265299", "title": "A specific radioimmunoassay for PGE2 using an antibody with high specificity and a sephadex LH-20 microcolumn for the separation of prostaglandins.", "content": "Antiserum against PGE2 was raised in rabbits following immunization with prostaglandin-hen-gamma-globulin conjugate. The antiserum exhibited 14% cross reactivity with PGE1 and far less cross-reaction with heterologous prostaglandins. A microcolumn of Sephadex LH-20 was used for a partial, but sufficient separation of PGE2 from PGE1 and a complete separation from heterologous prostaglandins to ensure a specific RIA for PGE2. The precision of the method in the rage 10-500 picograms showed a coefficient of variation varying between 4 and 13%. The detection limit was 10 picograms corresponding to 15 pg/ml of PGE2 in serum. In order to demonstrate the validity of the method values obtained for non-diuretic rat renal venous serum were compared with those obtained using the isotope derivative method of Bojesen & Buckhave (1972) on the same samples. The concentrations of PGE2 obtained were 239 +/- 25 pg/ml and 250 +/- 58 pg/ml, respectively.", "contents": "A specific radioimmunoassay for PGE2 using an antibody with high specificity and a sephadex LH-20 microcolumn for the separation of prostaglandins. Antiserum against PGE2 was raised in rabbits following immunization with prostaglandin-hen-gamma-globulin conjugate. The antiserum exhibited 14% cross reactivity with PGE1 and far less cross-reaction with heterologous prostaglandins. A microcolumn of Sephadex LH-20 was used for a partial, but sufficient separation of PGE2 from PGE1 and a complete separation from heterologous prostaglandins to ensure a specific RIA for PGE2. The precision of the method in the rage 10-500 picograms showed a coefficient of variation varying between 4 and 13%. The detection limit was 10 picograms corresponding to 15 pg/ml of PGE2 in serum. In order to demonstrate the validity of the method values obtained for non-diuretic rat renal venous serum were compared with those obtained using the isotope derivative method of Bojesen & Buckhave (1972) on the same samples. The concentrations of PGE2 obtained were 239 +/- 25 pg/ml and 250 +/- 58 pg/ml, respectively."} {"id": "PMID:1265337", "title": "Dose related changes in tissue morphine concentration.", "content": "Rats were injected with morphine-6(3)H diluted with increasing amounts of non-radiolabelled morphine. The entry of the isotope into the brain and various tissues was measured by combustion in a tissue oxidizer. The relative distribution of morphine between the blood and brain remained constant at about 5.5:1 over the range of doses studied (0.07 - 10.0 mg/kg). No dose related differential effects on morphine uptake were evident in central tissues, with the exception of the hypothalamus which exhibited a disproportionately greater uptake. Among the noncentral tissues, kidney and liver showed the greatest dose related increases in uptake.", "contents": "Dose related changes in tissue morphine concentration. Rats were injected with morphine-6(3)H diluted with increasing amounts of non-radiolabelled morphine. The entry of the isotope into the brain and various tissues was measured by combustion in a tissue oxidizer. The relative distribution of morphine between the blood and brain remained constant at about 5.5:1 over the range of doses studied (0.07 - 10.0 mg/kg). No dose related differential effects on morphine uptake were evident in central tissues, with the exception of the hypothalamus which exhibited a disproportionately greater uptake. Among the noncentral tissues, kidney and liver showed the greatest dose related increases in uptake."} {"id": "PMID:1265338", "title": "Disposition of (3H) benzoylnorecgonine (cocaine metabolite) in the rat.", "content": "The preparation and disposition of (3H) benzoylnorecgonine, which has potent stimulant activity intracisternally in the rat, has been described. The T1/2 of (3H) benzoylnorecgonine in brain and plasma of rats injected with a 10 mg kg-1 i.v. dose were 3.0, 1.2 h respectively. The ratio of mean peak concentration in brain to that in plasma was 0.03. No metabolites of benzoylnorecgonine were observed in rat brain. The mean percentage of dose excreted in urine and feces in 96 h were 85 and 2.2, respectively, with major excretion (82.5%) occurring within 24 h in urine. Approximately 90% of the radioactivity in urine was due to unmetabolised benzoylnorecgonine and 10% due to an unidentified metabolite. Norecgonine was not detected as a urinary metabolite.", "contents": "Disposition of (3H) benzoylnorecgonine (cocaine metabolite) in the rat. The preparation and disposition of (3H) benzoylnorecgonine, which has potent stimulant activity intracisternally in the rat, has been described. The T1/2 of (3H) benzoylnorecgonine in brain and plasma of rats injected with a 10 mg kg-1 i.v. dose were 3.0, 1.2 h respectively. The ratio of mean peak concentration in brain to that in plasma was 0.03. No metabolites of benzoylnorecgonine were observed in rat brain. The mean percentage of dose excreted in urine and feces in 96 h were 85 and 2.2, respectively, with major excretion (82.5%) occurring within 24 h in urine. Approximately 90% of the radioactivity in urine was due to unmetabolised benzoylnorecgonine and 10% due to an unidentified metabolite. Norecgonine was not detected as a urinary metabolite."} {"id": "PMID:1265340", "title": "Characterization of three monohydroxyacid and two dihydroxyacid metabolites of delta 1-tetrahydrocannabinol in mouse liver.", "content": "Delta 1-Tetrahydrocannabinol-7-oic acid, together with its 2 inches-, 3 inches- and 6 alpha-monohydroxy and 2 inches, 6 alpha- and 3 inches, 6 alpha-dihydroxy derivatives have been characterized by combined gas chromatography and mass spectrometry in organic extracts of mouse liver following large doses of delta 1-tetrahydrocannabinol.", "contents": "Characterization of three monohydroxyacid and two dihydroxyacid metabolites of delta 1-tetrahydrocannabinol in mouse liver. Delta 1-Tetrahydrocannabinol-7-oic acid, together with its 2 inches-, 3 inches- and 6 alpha-monohydroxy and 2 inches, 6 alpha- and 3 inches, 6 alpha-dihydroxy derivatives have been characterized by combined gas chromatography and mass spectrometry in organic extracts of mouse liver following large doses of delta 1-tetrahydrocannabinol."} {"id": "PMID:1265341", "title": "Sub-lethal effects on offspring of male rats treated with methadone before mating.", "content": "We have observed that ingestion of methadone (METH) by male rats prior to mating greatly increased the neonatal death rate of their offspring. In this experiment male rats were allowed drinking water containing METH for 24 hrs, alone or in the presence of females, and then mated with drug-naive females. When both males and females were exposed to METH the frequency of matings was decreased. Offspring of METH males were lighter in weight at birth and at weaning, particularly if their sires had been exposed to females during the period of METH ingestion. Although the neonatal death rate of the METH offspring was more than twice that of controls this difference was not statistically significant. The enhancement of METH effects by concurrent exposure to females leads us to propose that the locus of action of METH is the developing spermatozoa.", "contents": "Sub-lethal effects on offspring of male rats treated with methadone before mating. We have observed that ingestion of methadone (METH) by male rats prior to mating greatly increased the neonatal death rate of their offspring. In this experiment male rats were allowed drinking water containing METH for 24 hrs, alone or in the presence of females, and then mated with drug-naive females. When both males and females were exposed to METH the frequency of matings was decreased. Offspring of METH males were lighter in weight at birth and at weaning, particularly if their sires had been exposed to females during the period of METH ingestion. Although the neonatal death rate of the METH offspring was more than twice that of controls this difference was not statistically significant. The enhancement of METH effects by concurrent exposure to females leads us to propose that the locus of action of METH is the developing spermatozoa."} {"id": "PMID:1265342", "title": "Allergic bronchoconstriction and its drug-induced reversal in anesthetized, ovalbumin-sensitized cats.", "content": "Cats, once thought to possess little immunological responsiveness, have recently been shown to manifest a wide range of immunologic reactions. Sensitization of cats with ovalbumin rendered the animals capable, after a latency period of 40 to 60 days, of anaphylactic shock upon intravenous challenge. Physiologically the response is characterized by bronchoconstriction as evidenced by an increase in airways resistance. This response was ameliorated by intravenous administration of either aminophylline or isoproterenol. Other reactions elicited upon challenge were dyspnea, cyanosis, and in some instances death. The parameters of the allergic response corresponded with those reported in previous studies of other experimental models of allergic bronchoconstriction.", "contents": "Allergic bronchoconstriction and its drug-induced reversal in anesthetized, ovalbumin-sensitized cats. Cats, once thought to possess little immunological responsiveness, have recently been shown to manifest a wide range of immunologic reactions. Sensitization of cats with ovalbumin rendered the animals capable, after a latency period of 40 to 60 days, of anaphylactic shock upon intravenous challenge. Physiologically the response is characterized by bronchoconstriction as evidenced by an increase in airways resistance. This response was ameliorated by intravenous administration of either aminophylline or isoproterenol. Other reactions elicited upon challenge were dyspnea, cyanosis, and in some instances death. The parameters of the allergic response corresponded with those reported in previous studies of other experimental models of allergic bronchoconstriction."} {"id": "PMID:1265343", "title": "An evaluation of the hot plate technique to study narcotic antagonists.", "content": "The mouse hot plate model, with slight differences from the way it is used to study narcotic analgesics, was evaluated as a method for determining the oral effectiveness, relative potency and duration of action of two standard narcotic antagonists, naloxone and naltrexone, and a new agent, 6-desoxy-6-methylene-naltrexone (ORF 11676). Naltrexone and ORF 11676 were found to be more effective orally than naloxone. Naltrexone and ORF 11676 were equipotent by 3 routes of administration and both were more potent than naloxone. Naloxone produced a significantly shorter duration of action than the other two drugs. It was concluded that the mouse hot plate method, used to detect and characterize the activity of narcotic antagonists, provides information compatible with that obtained in other species, including man.", "contents": "An evaluation of the hot plate technique to study narcotic antagonists. The mouse hot plate model, with slight differences from the way it is used to study narcotic analgesics, was evaluated as a method for determining the oral effectiveness, relative potency and duration of action of two standard narcotic antagonists, naloxone and naltrexone, and a new agent, 6-desoxy-6-methylene-naltrexone (ORF 11676). Naltrexone and ORF 11676 were found to be more effective orally than naloxone. Naltrexone and ORF 11676 were equipotent by 3 routes of administration and both were more potent than naloxone. Naloxone produced a significantly shorter duration of action than the other two drugs. It was concluded that the mouse hot plate method, used to detect and characterize the activity of narcotic antagonists, provides information compatible with that obtained in other species, including man."} {"id": "PMID:1265344", "title": "Acetylcholine induced alterations of 32Pi incorporation into phospholipids: lack of effects in human term placenta.", "content": "Fragments of noninnervated human placenta, a tissue rich in acetylcholine were incubated with 32Pi and drugs which modify cholinergic functions. The incorporation of 32Pi into placental polar phospholipids was measured in the presence or absence of 1X10(-4)M exogenous ACh. Particular attention was paid to phosphatidic acid, phosphatidyl inositol and phosphatidyl choline. There was no change in the intensity of labelling of any of the phospholipids due to the presence of ACh.", "contents": "Acetylcholine induced alterations of 32Pi incorporation into phospholipids: lack of effects in human term placenta. Fragments of noninnervated human placenta, a tissue rich in acetylcholine were incubated with 32Pi and drugs which modify cholinergic functions. The incorporation of 32Pi into placental polar phospholipids was measured in the presence or absence of 1X10(-4)M exogenous ACh. Particular attention was paid to phosphatidic acid, phosphatidyl inositol and phosphatidyl choline. There was no change in the intensity of labelling of any of the phospholipids due to the presence of ACh."} {"id": "PMID:1265345", "title": "Influence of thyroid hormone on norepinephrine metabolism in rat brain during maturation.", "content": "The effect of thyroid hormone on norepinephrine (NE) metabolism was investigated in various regions of the developing rat brain. Neonatal hypothyroidism, induced by daily propylthiouracil injection starting at birth, caused an increase in NE levels in the brain stem and hypothalamus. The turnover of brain NE, as indicated by its rate of depletion following alpha-methyl-p-tyrosine administration, was decreased in the hypothalamus of 30-day-old hypothyroid rats but was unchanged in the brain stem and basal ganglia. The activities of monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT) were decreased in certain brain regions of hypothyroid rats. The data suggest that thyroid hormone may influence the ontogenic patterns of NE metabolism in the brain.", "contents": "Influence of thyroid hormone on norepinephrine metabolism in rat brain during maturation. The effect of thyroid hormone on norepinephrine (NE) metabolism was investigated in various regions of the developing rat brain. Neonatal hypothyroidism, induced by daily propylthiouracil injection starting at birth, caused an increase in NE levels in the brain stem and hypothalamus. The turnover of brain NE, as indicated by its rate of depletion following alpha-methyl-p-tyrosine administration, was decreased in the hypothalamus of 30-day-old hypothyroid rats but was unchanged in the brain stem and basal ganglia. The activities of monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT) were decreased in certain brain regions of hypothyroid rats. The data suggest that thyroid hormone may influence the ontogenic patterns of NE metabolism in the brain."} {"id": "PMID:1265346", "title": "Effects of solid food on blood levels of alcohol in man.", "content": "Forty-five ml of 95% alcohol, diluted to 150 ml with orange juice, was taken orally by six adult male volunteers under the following conditions: A (fasting), B (following a light breakfast), C (following a heavy breakfast), D (following a steak meal), E (alcohol 1 hr after a heavy breakfast), and F (alcohol 1 hr before a heavy breakfast). Using treatment A as a reference, the average area under the blood alcohol, time curve was reduced by 36, 63, 55, 56, and 18% for treatment B through F, respectively. The reduction in area is attributed to two factors: (a) food reduced the efficiency of absorption of alcohol; and (b) food reduced the rate of absorption of alcohol, which, coupled with the operation of Michaelis-Menten elimination kinetics, contributed to the reduction in area. The latter effect is a result of changes in the ratio: instantaneous rate of metabolism/amount of alcohol in the body, which results in a smaller area when the rate of absorption is slow than when the rate of absorption is rapid. Using treatment A as a reference, the ratio of the average peak alcohol concentrations were: 1.0, 0.72, 0.35, 0.50, 0.49 and 1.11 for treatments A through F, respectively.", "contents": "Effects of solid food on blood levels of alcohol in man. Forty-five ml of 95% alcohol, diluted to 150 ml with orange juice, was taken orally by six adult male volunteers under the following conditions: A (fasting), B (following a light breakfast), C (following a heavy breakfast), D (following a steak meal), E (alcohol 1 hr after a heavy breakfast), and F (alcohol 1 hr before a heavy breakfast). Using treatment A as a reference, the average area under the blood alcohol, time curve was reduced by 36, 63, 55, 56, and 18% for treatment B through F, respectively. The reduction in area is attributed to two factors: (a) food reduced the efficiency of absorption of alcohol; and (b) food reduced the rate of absorption of alcohol, which, coupled with the operation of Michaelis-Menten elimination kinetics, contributed to the reduction in area. The latter effect is a result of changes in the ratio: instantaneous rate of metabolism/amount of alcohol in the body, which results in a smaller area when the rate of absorption is slow than when the rate of absorption is rapid. Using treatment A as a reference, the ratio of the average peak alcohol concentrations were: 1.0, 0.72, 0.35, 0.50, 0.49 and 1.11 for treatments A through F, respectively."} {"id": "PMID:1265347", "title": "Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. Biochemical and clinical response to therapy with pyridoxine.", "content": "Ten individuals having a severe clinical status associated with the carpal tunnel syndrome were selected for treatment with pyridoxine. The status of vitamin B6, as pyridoxal phosphate, was determined by the specific activities of the glutamic oxaloacetic transaminase of the erythrocytes (EGOT). Before treatment, the patients showed a deficiency of vitamin B6 as determined by 1) a comparison of the specific activities of EGOT with those of a control group (P less than 0.001); and 2) a differential assay based upon the principle of unsaturation and saturation of a Coenzyme-Apoenzyme System (CAS), as applied to EGOT. These patients were treated with pyridoxine, and the specific activities of EGOT were determined after 2 and 4 weeks. Not only was there a disappearance of the deficiency of pyridoxal phosphate, but the level of EGOT activity increased 55-68% during 2-4 weeks, respectively. More apoenzyme was apparently biosynthesized, because the specific activities were significantly higher than before therapy (P less than 0.001/4 wks). Clinical evaluation showed a great improvement in their status, and anticipated surgery for some of the patients became unnecessary. It is concluded that patients with a severe syndrome including the carpal tunnel defect have a deficiency of vitamin B6, and that both the syndrome and the deficiency are relived by therapy with pyridoxine.", "contents": "Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. Biochemical and clinical response to therapy with pyridoxine. Ten individuals having a severe clinical status associated with the carpal tunnel syndrome were selected for treatment with pyridoxine. The status of vitamin B6, as pyridoxal phosphate, was determined by the specific activities of the glutamic oxaloacetic transaminase of the erythrocytes (EGOT). Before treatment, the patients showed a deficiency of vitamin B6 as determined by 1) a comparison of the specific activities of EGOT with those of a control group (P less than 0.001); and 2) a differential assay based upon the principle of unsaturation and saturation of a Coenzyme-Apoenzyme System (CAS), as applied to EGOT. These patients were treated with pyridoxine, and the specific activities of EGOT were determined after 2 and 4 weeks. Not only was there a disappearance of the deficiency of pyridoxal phosphate, but the level of EGOT activity increased 55-68% during 2-4 weeks, respectively. More apoenzyme was apparently biosynthesized, because the specific activities were significantly higher than before therapy (P less than 0.001/4 wks). Clinical evaluation showed a great improvement in their status, and anticipated surgery for some of the patients became unnecessary. It is concluded that patients with a severe syndrome including the carpal tunnel defect have a deficiency of vitamin B6, and that both the syndrome and the deficiency are relived by therapy with pyridoxine."} {"id": "PMID:1265348", "title": "Experimental bovine Trichophyton verrucosum infection. Comparison of the rate of epidermal cell proliferation and keratinisation in non-infected and reinoculated cattle.", "content": "The rate of epidermal cell renewal in normal bovine skin and that reinoculated with Trichophyton verrucosum was measured using a radioautographic technique. The transit times of both nucleated and fully keratinised cells were measured in sequential biopsy samples removed at predetermined periods after intradermal inoculation with radio-labelled isotopes. The total time taken for cells of the basal layer to travel to the point of desquamation in the stratum corneum was 18 days in normal cattle. In similar areas on cattle that had been reinoculated with T verrucosum the total epidermal cell renewal time was reduced to 12 days. Increased protein synthesis, as measured by incorporation of radio-labelled nucleoside was evident in basal cells within 24 h of reinoculation with the fungus. The nucleated epidermal cell thickness had almost doubled in areas of reinoculated skin within 72 h and increased cell proliferation was maintained for at least 10 days. Desquamation of the thickened stratum corneum had occurred within seven days of reinoculation with the fungus.", "contents": "Experimental bovine Trichophyton verrucosum infection. Comparison of the rate of epidermal cell proliferation and keratinisation in non-infected and reinoculated cattle. The rate of epidermal cell renewal in normal bovine skin and that reinoculated with Trichophyton verrucosum was measured using a radioautographic technique. The transit times of both nucleated and fully keratinised cells were measured in sequential biopsy samples removed at predetermined periods after intradermal inoculation with radio-labelled isotopes. The total time taken for cells of the basal layer to travel to the point of desquamation in the stratum corneum was 18 days in normal cattle. In similar areas on cattle that had been reinoculated with T verrucosum the total epidermal cell renewal time was reduced to 12 days. Increased protein synthesis, as measured by incorporation of radio-labelled nucleoside was evident in basal cells within 24 h of reinoculation with the fungus. The nucleated epidermal cell thickness had almost doubled in areas of reinoculated skin within 72 h and increased cell proliferation was maintained for at least 10 days. Desquamation of the thickened stratum corneum had occurred within seven days of reinoculation with the fungus."} {"id": "PMID:1265349", "title": "Plasma bile acid elevation following CCI4 induced liver damage in dogs, sheep, calves and ponies.", "content": "Plasma bile acid concentration was determined in normal dogs,sheep, calves and ponies for three days before and six days after liver damage, induced by carbon tetrachloride. In all species, a significant increase in plasma bile acid concentration was associated with a concomitant significant increase in plasma sorbitol dehydrogenase and transferase activity. Plasma bilirubin also significantly increased in all animals except the dogs. Results suggested that plasma bile acid levels could be used to test liver function in domestic animals.", "contents": "Plasma bile acid elevation following CCI4 induced liver damage in dogs, sheep, calves and ponies. Plasma bile acid concentration was determined in normal dogs,sheep, calves and ponies for three days before and six days after liver damage, induced by carbon tetrachloride. In all species, a significant increase in plasma bile acid concentration was associated with a concomitant significant increase in plasma sorbitol dehydrogenase and transferase activity. Plasma bilirubin also significantly increased in all animals except the dogs. Results suggested that plasma bile acid levels could be used to test liver function in domestic animals."} {"id": "PMID:1265350", "title": "Use of pharmacokinetics to predict the distribution of pantothenate in dogs.", "content": "On the basis of plasma concentrations of pantothen[14C]ate, after its intravenous administration, a three compartment open model was proposed to predict the pharmacokinetics of pantothenate in dogs. The model assumed a central compartment comprising the plasma and other extracellular fluids, and distribution into two other peripheral compartments, one of which included the liver. Elimination of unchanged pantothenate was assumed to occur by metabolism from the compartment which included the liver. Distribution of pantothen[14C]ate from the plasma compartment into the liver compartment was shown to be very rapid; during 10 min after intravenous administration about 80 per cent of the dose had been cleared from the plasma compartment. The model successfully predicted the influence (first pass effect) of the liver on the fraction of an oral dose which reached the peripheral plasma unchanged.", "contents": "Use of pharmacokinetics to predict the distribution of pantothenate in dogs. On the basis of plasma concentrations of pantothen[14C]ate, after its intravenous administration, a three compartment open model was proposed to predict the pharmacokinetics of pantothenate in dogs. The model assumed a central compartment comprising the plasma and other extracellular fluids, and distribution into two other peripheral compartments, one of which included the liver. Elimination of unchanged pantothenate was assumed to occur by metabolism from the compartment which included the liver. Distribution of pantothen[14C]ate from the plasma compartment into the liver compartment was shown to be very rapid; during 10 min after intravenous administration about 80 per cent of the dose had been cleared from the plasma compartment. The model successfully predicted the influence (first pass effect) of the liver on the fraction of an oral dose which reached the peripheral plasma unchanged."} {"id": "PMID:1265351", "title": "The use of a liver biopsy technique for investigating the effects of hexacholrobenzene on some drug-metabolising enzymes in sheep.", "content": "Several parameters of drug-metabolising capacity were measured in samples taken from various regions of the sheep liver. A statistically significant difference of 10 per cent between mean values of enzyme activities of the ventral and dorsal lobes was found. This could be ignored when compared with the expected treatment effect. It is concluded that the biopsy technique provides a sufficiently representative sample of the whole liver for use in studies of the type described. The results also indicated that the liver enzyme levels of young lambs were lower than those of older lambs and adult sheep. Sheep dosed with hexachlorobenzene (hcb) showed increased activities of aniline hydroxylase and 4-nitroanisole O-demethylase but not of the NADPH-independent esterases. It is concluded that HCB induces the drug-metabolising enzymes of sheep liver.", "contents": "The use of a liver biopsy technique for investigating the effects of hexacholrobenzene on some drug-metabolising enzymes in sheep. Several parameters of drug-metabolising capacity were measured in samples taken from various regions of the sheep liver. A statistically significant difference of 10 per cent between mean values of enzyme activities of the ventral and dorsal lobes was found. This could be ignored when compared with the expected treatment effect. It is concluded that the biopsy technique provides a sufficiently representative sample of the whole liver for use in studies of the type described. The results also indicated that the liver enzyme levels of young lambs were lower than those of older lambs and adult sheep. Sheep dosed with hexachlorobenzene (hcb) showed increased activities of aniline hydroxylase and 4-nitroanisole O-demethylase but not of the NADPH-independent esterases. It is concluded that HCB induces the drug-metabolising enzymes of sheep liver."} {"id": "PMID:1265352", "title": "The ecology of the free living stages of Nematodirus filicollis.", "content": "The development and survival of the eggs of Nematodirus filicollis placed on grass plots over a period of a year were studied. Development took place at every season although it was more rapid in the warmer months. Yields of larvae were highest from eggs placed outside during February, March and April. Larvae persisted for two to two and a half years after eggs were placed on the pastures. The extraordinary persistence of the eggs and larvae of N filicollis makes control of the parasite difficult.", "contents": "The ecology of the free living stages of Nematodirus filicollis. The development and survival of the eggs of Nematodirus filicollis placed on grass plots over a period of a year were studied. Development took place at every season although it was more rapid in the warmer months. Yields of larvae were highest from eggs placed outside during February, March and April. Larvae persisted for two to two and a half years after eggs were placed on the pastures. The extraordinary persistence of the eggs and larvae of N filicollis makes control of the parasite difficult."} {"id": "PMID:1265353", "title": "Intranasal infection with Bordetella bronchiseptica in gnotobiotic piglets.", "content": "Nineteen gnotobiotic piglets, four to six days old, from three different litters, were inoculated intranasally on three consecutive days with a pure culture of Bordetella bronchiseptica. Necropsy 10 to 30 days after inoculation revealed atrophic rhinitis lesions in all and pneumonia in 13 (73 per cent)infected piglets. One died of septicaemia two days after inoculation. Agglutinating antibodies were detected in the sera of all piglets necropsied from 17 to 30 days after inoculation. Five control piglets showed no lesions or serological changes.", "contents": "Intranasal infection with Bordetella bronchiseptica in gnotobiotic piglets. Nineteen gnotobiotic piglets, four to six days old, from three different litters, were inoculated intranasally on three consecutive days with a pure culture of Bordetella bronchiseptica. Necropsy 10 to 30 days after inoculation revealed atrophic rhinitis lesions in all and pneumonia in 13 (73 per cent)infected piglets. One died of septicaemia two days after inoculation. Agglutinating antibodies were detected in the sera of all piglets necropsied from 17 to 30 days after inoculation. Five control piglets showed no lesions or serological changes."} {"id": "PMID:1265354", "title": "Experimentally produced calf pneumonia.", "content": "Experimental pneumonia was produced in calves by the endobronchial inoculation of pneumonic lung homogenates. Irradiated homogenates produced minimal pneumonia. Ampicillin treatment of the homogenates and the experimental calves reduced the extent of pneumonia. Treatment with tylosin tartrate prevented experimental pneumonia. These results suggest that the total pneumonia was due to organisms susceptible to tylosin tartrate and that the residual pneumonia remaining after ampicillin treatment was due to organisms susceptible to tylosin tartrate but not to ampicillin. Of the organisms isolated from the lungs, the ones in this latter category most likely to be responsible are Mycoplasma dispar and ureaplasmas (T-mycoplasmas).", "contents": "Experimentally produced calf pneumonia. Experimental pneumonia was produced in calves by the endobronchial inoculation of pneumonic lung homogenates. Irradiated homogenates produced minimal pneumonia. Ampicillin treatment of the homogenates and the experimental calves reduced the extent of pneumonia. Treatment with tylosin tartrate prevented experimental pneumonia. These results suggest that the total pneumonia was due to organisms susceptible to tylosin tartrate and that the residual pneumonia remaining after ampicillin treatment was due to organisms susceptible to tylosin tartrate but not to ampicillin. Of the organisms isolated from the lungs, the ones in this latter category most likely to be responsible are Mycoplasma dispar and ureaplasmas (T-mycoplasmas)."} {"id": "PMID:1265355", "title": "The effects of nitroxynil on the survival, growth and morphology of Fasciola hepatica in sheep.", "content": "Groups of sheep were experimentally infected with Fasciola hepatica and treated with nitroxynil at 10 mg/kg given subcutaneously at intervals of up to 70 days later. Effects on fluke burden, weight, morphology, egg production and hatchability were recorded. The results showed that the efficacy of nitroxynil and the occurrence of structurally abnormal flukes were directly proportional to the age of infection at treatment. Treatment also deleteriously affected fluke growth and egg hatchability and reduced faecal egg counts.", "contents": "The effects of nitroxynil on the survival, growth and morphology of Fasciola hepatica in sheep. Groups of sheep were experimentally infected with Fasciola hepatica and treated with nitroxynil at 10 mg/kg given subcutaneously at intervals of up to 70 days later. Effects on fluke burden, weight, morphology, egg production and hatchability were recorded. The results showed that the efficacy of nitroxynil and the occurrence of structurally abnormal flukes were directly proportional to the age of infection at treatment. Treatment also deleteriously affected fluke growth and egg hatchability and reduced faecal egg counts."} {"id": "PMID:1265356", "title": "The involvement of biotin in preventing the fatty liver and kidney syndrome in chicks.", "content": "Three experiments were carried out to investigate the involvement of vitamins in the fatty liver and kidney syndrome. The compounds studied, singly and in combination, were thiamin, riboflavin, nicotinic acid, pyridoxine, pantothenic acid, biotin, folic acid vitamin B12, ascorbic acid, choline and inositol and of these, only biotin prevented the syndrome. The minimum levels of supplemental dietary biotin required to prevent mortality varied from 0-05 to 0-15 mg/kg, depending on the diet. These levels were higher than the amounts required for maximum liveweight.", "contents": "The involvement of biotin in preventing the fatty liver and kidney syndrome in chicks. Three experiments were carried out to investigate the involvement of vitamins in the fatty liver and kidney syndrome. The compounds studied, singly and in combination, were thiamin, riboflavin, nicotinic acid, pyridoxine, pantothenic acid, biotin, folic acid vitamin B12, ascorbic acid, choline and inositol and of these, only biotin prevented the syndrome. The minimum levels of supplemental dietary biotin required to prevent mortality varied from 0-05 to 0-15 mg/kg, depending on the diet. These levels were higher than the amounts required for maximum liveweight."} {"id": "PMID:1265357", "title": "The effect of exercise on the lactic dehydrogenase and creatine kinase isoenzyme composition of horse serum.", "content": "The distribution of lactic dehydrogenase, aldolase and creatine kinase in various horse tissues was determined. Using polyacrylamide gel electrophoresis the lactic dehydrogenase and creatine kinase isoenzyme composition of horse serum, taken before and after exercise, was studied. Horse tissue isoenzyme patterns were also obtained. By comparing tissue and serum patterns, skeletal muscle was found to be the tissue of origin of the increase in serum lactic dehydrogenase and creatine kinase observed after exercise.", "contents": "The effect of exercise on the lactic dehydrogenase and creatine kinase isoenzyme composition of horse serum. The distribution of lactic dehydrogenase, aldolase and creatine kinase in various horse tissues was determined. Using polyacrylamide gel electrophoresis the lactic dehydrogenase and creatine kinase isoenzyme composition of horse serum, taken before and after exercise, was studied. Horse tissue isoenzyme patterns were also obtained. By comparing tissue and serum patterns, skeletal muscle was found to be the tissue of origin of the increase in serum lactic dehydrogenase and creatine kinase observed after exercise."} {"id": "PMID:1265358", "title": "Relation between the toxogenicity and pyogenicity of Corynebacterium ovis in experimentally infected mice.", "content": "Suspensions of Corynebacterium ovis subjected to physical and chemical treatment failed to kill inoculated mice but were able to produce sterile pyogenic lesions. It appears that the exotoxin is different from the pyogenic factor and that the latter is attached to a heat-stable substance in the bacterial cell. Mice immunised with antitoxin showed local non-spreading lesions when subsequenly inoculated with washed C ovis cells while unprotected control mice showed a spreading type of infection when similarly injected. Antitoxin did not prevent the formation of pus but hindered the spread of infection from the site of inoculation to the internal organs.", "contents": "Relation between the toxogenicity and pyogenicity of Corynebacterium ovis in experimentally infected mice. Suspensions of Corynebacterium ovis subjected to physical and chemical treatment failed to kill inoculated mice but were able to produce sterile pyogenic lesions. It appears that the exotoxin is different from the pyogenic factor and that the latter is attached to a heat-stable substance in the bacterial cell. Mice immunised with antitoxin showed local non-spreading lesions when subsequenly inoculated with washed C ovis cells while unprotected control mice showed a spreading type of infection when similarly injected. Antitoxin did not prevent the formation of pus but hindered the spread of infection from the site of inoculation to the internal organs."} {"id": "PMID:1265359", "title": "The establishment and duration of Fasciola hepatica infections in two strains of rats and the development of acquired resistance.", "content": "Male and female rats of the inbred Piebald Virol Glaxo ( PVG) and Sprague Dawley (SD) strains were infected with 20 metacercariae of Fasciola hepatica. Three months after infection there was a highly significant difference (P LESS THAN 0-001) in the fluke burden of the two strains. The PVG rats (average 9-4 flukes) were more susceptible than the SD strain (average 2-8 flukes). The PVG males (11-6 flukes) were also found to be significantly more susceptible than the PVG females (average 7-2 flukes) whereas the sex of the SD rats did not affect the fluke burdens significantly. Seven to eight months after infection the PVG rats had eliminated their flukes. These 'self cured' PVG rats were significantly resistant to oral challenge with 20 metacercariae. In marked contrast the SD rats had not eliminated their flukes at the termination of the experiment 12 months after infection.", "contents": "The establishment and duration of Fasciola hepatica infections in two strains of rats and the development of acquired resistance. Male and female rats of the inbred Piebald Virol Glaxo ( PVG) and Sprague Dawley (SD) strains were infected with 20 metacercariae of Fasciola hepatica. Three months after infection there was a highly significant difference (P LESS THAN 0-001) in the fluke burden of the two strains. The PVG rats (average 9-4 flukes) were more susceptible than the SD strain (average 2-8 flukes). The PVG males (11-6 flukes) were also found to be significantly more susceptible than the PVG females (average 7-2 flukes) whereas the sex of the SD rats did not affect the fluke burdens significantly. Seven to eight months after infection the PVG rats had eliminated their flukes. These 'self cured' PVG rats were significantly resistant to oral challenge with 20 metacercariae. In marked contrast the SD rats had not eliminated their flukes at the termination of the experiment 12 months after infection."} {"id": "PMID:1265360", "title": "A possible relationship between haemonchosis and haemoglobin polymorphism in Merino sheep in Kenya.", "content": "It is known that sheep show polymorphism for haemoglobin in that three phenotypes (HbA, HbB AND HbAB) are normally found. Since it has been suggested, on the basis of haematological values, that HbA type sheep are more able to survive in Haemonchus contortus endemic environments, a preliminary study was conducted on the performance of set-stocked Merino ewes and lambs in relation to their haemoglobin phenotypes. The results provided some evidence that, in Merino sheep at least, those with HbA type show 'self-cure' more frequently and effectively than those with HbB and HbAB types. Examination of the PCV values and total body weights of Merino eres showed a similar trend, ie, the HbA types had the highest haematological parameters and the heaviest body weights, while the HbB types were consistently lowest. It would appear that the practical significance of these results justifies investigation on a larger scale.", "contents": "A possible relationship between haemonchosis and haemoglobin polymorphism in Merino sheep in Kenya. It is known that sheep show polymorphism for haemoglobin in that three phenotypes (HbA, HbB AND HbAB) are normally found. Since it has been suggested, on the basis of haematological values, that HbA type sheep are more able to survive in Haemonchus contortus endemic environments, a preliminary study was conducted on the performance of set-stocked Merino ewes and lambs in relation to their haemoglobin phenotypes. The results provided some evidence that, in Merino sheep at least, those with HbA type show 'self-cure' more frequently and effectively than those with HbB and HbAB types. Examination of the PCV values and total body weights of Merino eres showed a similar trend, ie, the HbA types had the highest haematological parameters and the heaviest body weights, while the HbB types were consistently lowest. It would appear that the practical significance of these results justifies investigation on a larger scale."} {"id": "PMID:1265361", "title": "Some behavioural and physiological changes in pregnant goats and sheep during adaptation to laboratory conditions.", "content": "Eight goats and 12 sheep were examined during their first six to eight weeks in the laboratory. Plasma corticosteroid concentrations in four untamed goats and four untamed sheep were elevated during the first week but thereafter remained at basal values. In contrast, low corticosteroid concentrations were observed throughout in four tame goats and in four untamed sheep sampled only after they had been in the laboratory for two weeks. Plasma glucose concentrations were elevated during the first week in the untamed goats. In four partially tamed sheep a rise in heart rate which occurred transiently during handling for 4-6 min did not occur when these animals showed tame behaviour after two to three weeks, and in four untamed sheep a rise in plasma corticosteroid concentration, which occurred transiently when seven blood samples were taken in 90 min, did not occur when these sheep were judged to be tame after five to six weeks.", "contents": "Some behavioural and physiological changes in pregnant goats and sheep during adaptation to laboratory conditions. Eight goats and 12 sheep were examined during their first six to eight weeks in the laboratory. Plasma corticosteroid concentrations in four untamed goats and four untamed sheep were elevated during the first week but thereafter remained at basal values. In contrast, low corticosteroid concentrations were observed throughout in four tame goats and in four untamed sheep sampled only after they had been in the laboratory for two weeks. Plasma glucose concentrations were elevated during the first week in the untamed goats. In four partially tamed sheep a rise in heart rate which occurred transiently during handling for 4-6 min did not occur when these animals showed tame behaviour after two to three weeks, and in four untamed sheep a rise in plasma corticosteroid concentration, which occurred transiently when seven blood samples were taken in 90 min, did not occur when these sheep were judged to be tame after five to six weeks."} {"id": "PMID:1265362", "title": "Solanum malacoxylon poisoning in pigs.", "content": "Solanum malacoxylon was given orally to four pigs. The animals were examined clinically and subjected to post mortem examination. Macroscopic lesions were not seen with the exception of a small calcified plaque in the endocardium of one animal. Microscopic examinations revealed slight calcification of elastic fibres in the soft tissues. The pathological changes in the bones were extensive and are described in detail. The pigs showed minimal lesions at dose levels which cause considerable systemic calcification in cattle and sheep.", "contents": "Solanum malacoxylon poisoning in pigs. Solanum malacoxylon was given orally to four pigs. The animals were examined clinically and subjected to post mortem examination. Macroscopic lesions were not seen with the exception of a small calcified plaque in the endocardium of one animal. Microscopic examinations revealed slight calcification of elastic fibres in the soft tissues. The pathological changes in the bones were extensive and are described in detail. The pigs showed minimal lesions at dose levels which cause considerable systemic calcification in cattle and sheep."} {"id": "PMID:1265363", "title": "Method for concentrating antisera for preparing Mycoplasma growth inhibition discs.", "content": "Mycoplasma growth inhibiting antibody in rabbit anitsera was concentrated with a dry polyacrylamide gel. Discs prepared with such concentrated antisera inhibited only the homologous organism provided the antisera had been heated at 56 degrees C for 30 min, and when dried retained their potency during storage for over two years at 4 degrees C.", "contents": "Method for concentrating antisera for preparing Mycoplasma growth inhibition discs. Mycoplasma growth inhibiting antibody in rabbit anitsera was concentrated with a dry polyacrylamide gel. Discs prepared with such concentrated antisera inhibited only the homologous organism provided the antisera had been heated at 56 degrees C for 30 min, and when dried retained their potency during storage for over two years at 4 degrees C."} {"id": "PMID:1265364", "title": "Postnatal changes in the levels of 2,3-diaphosphoglycerate, reduced glutathione and some enzyme activities in the erythrocytes of lambs.", "content": "The concentration of 2,3-diphosphoglycerate, and the activities of the enzymes hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase and NADH-dependent methaemoglobin reductase in the erythrocytes of newborn and adult sheep were investigated. All the enzyme activities and the concentration of 2,3-diaphosphoglycerate were found to be significantly greater in the erythrocytes of newborn lambs than in those of adult sheep.", "contents": "Postnatal changes in the levels of 2,3-diaphosphoglycerate, reduced glutathione and some enzyme activities in the erythrocytes of lambs. The concentration of 2,3-diphosphoglycerate, and the activities of the enzymes hexokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase and NADH-dependent methaemoglobin reductase in the erythrocytes of newborn and adult sheep were investigated. All the enzyme activities and the concentration of 2,3-diaphosphoglycerate were found to be significantly greater in the erythrocytes of newborn lambs than in those of adult sheep."} {"id": "PMID:1265365", "title": "The levels of selenium and glutathione peroxidase activity in blood of sheep, cows and pigs.", "content": "The levels of selenium (Se) and glutathione peroxidase (GPX) in the blood of sheep, cows and pigs under farm conditions were examined. Sheep appear to form two distinct groups, namely high Se and GPX and low Se and GPX. The high group gave ranges of 133-249 ng/ml and 77-179 iu/g Hb for blood Se and GPX respectively, while the low group showed levels of 21-67 ng/ml and 2-20 iu/g Hb. Overall sheep blood showed a high correlation between Se and GPX (r = 0-92, P less than 0-001). Cow bloods formed one group, all having low Se and GPX levels except for a single outlier. Omitting this animal, the overall ranges were 9-72 ng/ml and 6-36 iu/g Hb for Se and GPX respectively. Blood Se and GPX activity were significantly correlated (r = 0-59, P less than 0-001). Pigs formed a single group also, with the difference that while their blood Se was high, the corresponding blood GPX activities were relatively low. Overall ranges were 93-193 ng/ml and 17-69 iu/g Hb for Se and GPX respectively. Correlation between blood Se level and GPX activity in this species was not significant (r = 0-27, P more than 0-1).", "contents": "The levels of selenium and glutathione peroxidase activity in blood of sheep, cows and pigs. The levels of selenium (Se) and glutathione peroxidase (GPX) in the blood of sheep, cows and pigs under farm conditions were examined. Sheep appear to form two distinct groups, namely high Se and GPX and low Se and GPX. The high group gave ranges of 133-249 ng/ml and 77-179 iu/g Hb for blood Se and GPX respectively, while the low group showed levels of 21-67 ng/ml and 2-20 iu/g Hb. Overall sheep blood showed a high correlation between Se and GPX (r = 0-92, P less than 0-001). Cow bloods formed one group, all having low Se and GPX levels except for a single outlier. Omitting this animal, the overall ranges were 9-72 ng/ml and 6-36 iu/g Hb for Se and GPX respectively. Blood Se and GPX activity were significantly correlated (r = 0-59, P less than 0-001). Pigs formed a single group also, with the difference that while their blood Se was high, the corresponding blood GPX activities were relatively low. Overall ranges were 93-193 ng/ml and 17-69 iu/g Hb for Se and GPX respectively. Correlation between blood Se level and GPX activity in this species was not significant (r = 0-27, P more than 0-1)."} {"id": "PMID:1265366", "title": "Estimating erythrocyte glyceraldehyde-3-phosphate dehydrogenase by a new method.", "content": "A semi-quantitative fluorimetric assay for glyceraldehyde-3-phosphate dehydrogenase has been described. This method was applied to a number of animal species and correlates well with the standard spectrophotometric method.", "contents": "Estimating erythrocyte glyceraldehyde-3-phosphate dehydrogenase by a new method. A semi-quantitative fluorimetric assay for glyceraldehyde-3-phosphate dehydrogenase has been described. This method was applied to a number of animal species and correlates well with the standard spectrophotometric method."} {"id": "PMID:1265411", "title": "[The action of somatotropic hormone on bone and on phospho-calcic metabolism].", "content": "The author reviews present knowledge concerning the action of somatotropic hormone on the kidney, the intestine, and on developmental changes in bone. He reviews, in particular, the controversial question of acromegalic osteoporosis and in this connexion considers the possibility of associated hyperparathyroidism.", "contents": "[The action of somatotropic hormone on bone and on phospho-calcic metabolism]. The author reviews present knowledge concerning the action of somatotropic hormone on the kidney, the intestine, and on developmental changes in bone. He reviews, in particular, the controversial question of acromegalic osteoporosis and in this connexion considers the possibility of associated hyperparathyroidism."} {"id": "PMID:1265412", "title": "[HL-A W27 antigen and atypical rheumatic pelvispondylitis].", "content": "The authors report 26 cases of atypical inflammatory rheumatism in which the discovery of HL-A W27 antigen indicated the possibility of atypical ankylosing spondylarthritis. These patients included 17 men and 9 women with an average age of 35.6 years. The clinical symptoms included :--pelvic or vetebral signs alone in 8 cases,--pelvic or vertebral signs combined with peripheral inflammatory rheumatism, the latter being always cleaarly evident, in 9 cases,--extravertebral signs alone without any involvement of the vertebral column or of the sacroiliac joints in 9 cases (8 cases of peripheral inflammatory rheumatism, 1 case of talalgia). The vertebral radiograms were normal in 84 percent of cases. The sacroiliac joints were clear radiologically in 65 percent of cases. In the other cases the lesions, generally unilateral, were extremely discrete. In all the cases, the Waaler-Rose reaction was negative. The therapeutic test with non-hormonal anti inflammatory products were generally positive. The evolution of the condition confirmed the diagnosis of rheumatic pelvispondylitis in 2 cases. The patients have been under observation for insufficient time to be sure whether all the cases presented represent authentic cases of ankylosing spondylarthritis that were at first atypical. The authors emphasize the high percentage of female cases (38 percent) the high frequency of extra-vertebral manifestations. They also emphasize the value of looking for HL-A W27 antigen in patients with atypical inflammatory rheumatism.", "contents": "[HL-A W27 antigen and atypical rheumatic pelvispondylitis]. The authors report 26 cases of atypical inflammatory rheumatism in which the discovery of HL-A W27 antigen indicated the possibility of atypical ankylosing spondylarthritis. These patients included 17 men and 9 women with an average age of 35.6 years. The clinical symptoms included :--pelvic or vetebral signs alone in 8 cases,--pelvic or vertebral signs combined with peripheral inflammatory rheumatism, the latter being always cleaarly evident, in 9 cases,--extravertebral signs alone without any involvement of the vertebral column or of the sacroiliac joints in 9 cases (8 cases of peripheral inflammatory rheumatism, 1 case of talalgia). The vertebral radiograms were normal in 84 percent of cases. The sacroiliac joints were clear radiologically in 65 percent of cases. In the other cases the lesions, generally unilateral, were extremely discrete. In all the cases, the Waaler-Rose reaction was negative. The therapeutic test with non-hormonal anti inflammatory products were generally positive. The evolution of the condition confirmed the diagnosis of rheumatic pelvispondylitis in 2 cases. The patients have been under observation for insufficient time to be sure whether all the cases presented represent authentic cases of ankylosing spondylarthritis that were at first atypical. The authors emphasize the high percentage of female cases (38 percent) the high frequency of extra-vertebral manifestations. They also emphasize the value of looking for HL-A W27 antigen in patients with atypical inflammatory rheumatism."} {"id": "PMID:1265413", "title": "[Role of vertebral hyperostosis in cervical myelopathies].", "content": "The authors analysed the case histories of 40 patients with cervical myelopathy and were struck by the frequency of associated vertebral hyperostosis (Forestier and Rot\u00e8s-Qu\u00e9rol disease). They found 17 cases in which dorsal vertebral hyperostosis was indiscutable and in which there was acquired stenosis of the cervical canal related to the bony proliferations that had developed on the anterior face of the cervical canal and to the type of cells described by Forestier and Rotes-Querol on the anterior and lateral faces of the vertebral column. According to the present authors these posterior growths occurred in a site that has not previously been described for hyperostosis. These growths are likened to those observed by Japanese neurosurgeons since 1960. Their particular interest concerns their role in pathology.", "contents": "[Role of vertebral hyperostosis in cervical myelopathies]. The authors analysed the case histories of 40 patients with cervical myelopathy and were struck by the frequency of associated vertebral hyperostosis (Forestier and Rot\u00e8s-Qu\u00e9rol disease). They found 17 cases in which dorsal vertebral hyperostosis was indiscutable and in which there was acquired stenosis of the cervical canal related to the bony proliferations that had developed on the anterior face of the cervical canal and to the type of cells described by Forestier and Rotes-Querol on the anterior and lateral faces of the vertebral column. According to the present authors these posterior growths occurred in a site that has not previously been described for hyperostosis. These growths are likened to those observed by Japanese neurosurgeons since 1960. Their particular interest concerns their role in pathology."} {"id": "PMID:1265414", "title": "[Atrioventricular blocks and rheumatoid arthritis].", "content": "Among 379 hospitalized cases of rheumatoid polyarthritis, 12 auriculo-ventricular blocks were detected between 1965 and 1975. The formation of a complete AV block is usually preceded by a branch block or a first degree block. During the installation of a pacemaker, hypoexcitability was usually noted. Four of the patients died. In the other 8 the evolution has been satisfactory over periods from 6 months to 4 years. Conduction disturbances were found in cases of polyarthritis of 10 years duration on the average. The articular lesions were normally diffuse with considerable lesions detectable radiologically. In many cases the frequency of extra-articular lesions indicated the severity of the rheumatic disease. From the anatomical point of view, histological lesions of rheumatoid polyarthritis were found : granuloma and arteritis in the myocardium. Only 8 authors have previously reported lesions of the donducting vessels at autopsies carried out on rheumatoid polyarthritis cases who had presented AV blocks. Except for Thery's case related to amylosis of the nodal tissue, rheumatoid granulomas occupied the whole or part of the nodal tissue. In elderly subjects suffering from rheumatoid arthritis, it was difficult to establish a strictly rheumatoid origin for the AV blocks observed, unless specific granulomas were discovered anatomically in the nodal tissue.", "contents": "[Atrioventricular blocks and rheumatoid arthritis]. Among 379 hospitalized cases of rheumatoid polyarthritis, 12 auriculo-ventricular blocks were detected between 1965 and 1975. The formation of a complete AV block is usually preceded by a branch block or a first degree block. During the installation of a pacemaker, hypoexcitability was usually noted. Four of the patients died. In the other 8 the evolution has been satisfactory over periods from 6 months to 4 years. Conduction disturbances were found in cases of polyarthritis of 10 years duration on the average. The articular lesions were normally diffuse with considerable lesions detectable radiologically. In many cases the frequency of extra-articular lesions indicated the severity of the rheumatic disease. From the anatomical point of view, histological lesions of rheumatoid polyarthritis were found : granuloma and arteritis in the myocardium. Only 8 authors have previously reported lesions of the donducting vessels at autopsies carried out on rheumatoid polyarthritis cases who had presented AV blocks. Except for Thery's case related to amylosis of the nodal tissue, rheumatoid granulomas occupied the whole or part of the nodal tissue. In elderly subjects suffering from rheumatoid arthritis, it was difficult to establish a strictly rheumatoid origin for the AV blocks observed, unless specific granulomas were discovered anatomically in the nodal tissue."} {"id": "PMID:1265430", "title": "Jejunal morphology and mucosal enzyme activity following intestinal shunt operation for obesity.", "content": "Jejunal biopsy in 33 patients before and after intestinal shunt operation for obesity has demonstrated that neither surface nor volume of the villi increase after surgery. Specific disaccharidase activity remained unchanged, and specific alkaline phosphatase activity increased slightly. There was a significant decrease in protein content in the postoperative biopsies. It is concluded that weight stabilization after the shunt operation is due to adaptive compensation in the ileal remnant.", "contents": "Jejunal morphology and mucosal enzyme activity following intestinal shunt operation for obesity. Jejunal biopsy in 33 patients before and after intestinal shunt operation for obesity has demonstrated that neither surface nor volume of the villi increase after surgery. Specific disaccharidase activity remained unchanged, and specific alkaline phosphatase activity increased slightly. There was a significant decrease in protein content in the postoperative biopsies. It is concluded that weight stabilization after the shunt operation is due to adaptive compensation in the ileal remnant."} {"id": "PMID:1265431", "title": "Routine and blind histological diagnoses on colonoscopic biopsies compared to clinical-colonoscopic observations in patients without and with colitis.", "content": "Of the 110 patients examined, complete agreement was found between the blind and routine histological studies in the sections from 69 patients (63%), between the blind histological study and that of colonoscopy in 66 patients (60%), and between the routine histological diagnoses and those of colonoscopy in 73 patients (66%). The diagnosis of a normal colonic mucosa was made by blind study on colonoscopic biopsies in 32 patients, by the routine one in 36 patients, and by clinical-colonoscopic examination in 40 cases, the percentage of agreement with the colonoscopic diagnosis being 68 and 72, respectively. The diagnosis of unspecific non-ulcerative colitis was made by the blind histological study in 43 patients, by the routine histological examination in 58 cases, and by colonoscopy in 41 patients. The percentage of agreement between the histological studies and the clinical-colonoscopic diagnoses was 61 and 78, respectively. A diagnosis of ulcerative colitis was made by the blind histological study in 35 patients, by the routine histological examination in 16, and by colonoscopy in 27 cases. The percentages of agreement between the histological studies and the diagnoses by clinical-colonoscopic examination were 82 and 59, respectively. The differences in symptomatology between groups were small, except for a high occurrence of diarrhoea and blood in stool in ceses with ulcerative colitis, as evaluated by blind histological study. The findings stress the importance of following defined criteria for histological examination.", "contents": "Routine and blind histological diagnoses on colonoscopic biopsies compared to clinical-colonoscopic observations in patients without and with colitis. Of the 110 patients examined, complete agreement was found between the blind and routine histological studies in the sections from 69 patients (63%), between the blind histological study and that of colonoscopy in 66 patients (60%), and between the routine histological diagnoses and those of colonoscopy in 73 patients (66%). The diagnosis of a normal colonic mucosa was made by blind study on colonoscopic biopsies in 32 patients, by the routine one in 36 patients, and by clinical-colonoscopic examination in 40 cases, the percentage of agreement with the colonoscopic diagnosis being 68 and 72, respectively. The diagnosis of unspecific non-ulcerative colitis was made by the blind histological study in 43 patients, by the routine histological examination in 58 cases, and by colonoscopy in 41 patients. The percentage of agreement between the histological studies and the clinical-colonoscopic diagnoses was 61 and 78, respectively. A diagnosis of ulcerative colitis was made by the blind histological study in 35 patients, by the routine histological examination in 16, and by colonoscopy in 27 cases. The percentages of agreement between the histological studies and the diagnoses by clinical-colonoscopic examination were 82 and 59, respectively. The differences in symptomatology between groups were small, except for a high occurrence of diarrhoea and blood in stool in ceses with ulcerative colitis, as evaluated by blind histological study. The findings stress the importance of following defined criteria for histological examination."} {"id": "PMID:1265432", "title": "The diagnosis of colitis by colonoscopy with biopsy and X-ray examination. A blind comparative study.", "content": "The examinations were performed in 40 outpatients, of whom 21 were women. From the rectal and colonic mucosa 185 biopsies were obtained. The X-ray examination was performed within one week from the colonoscopy, using a conventional barium enema. A complete agreement between the colonoscopic diagnosis and that of the directed biopsy was found in 33 cases (80 per cent), and minor disagreements in 3 cases. A complete agreement between the colonoscopic and X-ray diagnoses was obtained in 22 patients (55 per cent), and minor disagreements in 16 cases, most of whom showed \"unspecific\" non-ulcerative colitis. In 3 cases with ulcerative colitis a normal colon was found by X-ray. A higher percentage of cases showed decreased haustration by X-ray examination than by colonoscopy, whereas a fairly equal percentage of ulceration was detected by the two methods. Erosions, mucus covering, oedema, vascular injection, and bleedings were not detected by X-ray examination.", "contents": "The diagnosis of colitis by colonoscopy with biopsy and X-ray examination. A blind comparative study. The examinations were performed in 40 outpatients, of whom 21 were women. From the rectal and colonic mucosa 185 biopsies were obtained. The X-ray examination was performed within one week from the colonoscopy, using a conventional barium enema. A complete agreement between the colonoscopic diagnosis and that of the directed biopsy was found in 33 cases (80 per cent), and minor disagreements in 3 cases. A complete agreement between the colonoscopic and X-ray diagnoses was obtained in 22 patients (55 per cent), and minor disagreements in 16 cases, most of whom showed \"unspecific\" non-ulcerative colitis. In 3 cases with ulcerative colitis a normal colon was found by X-ray. A higher percentage of cases showed decreased haustration by X-ray examination than by colonoscopy, whereas a fairly equal percentage of ulceration was detected by the two methods. Erosions, mucus covering, oedema, vascular injection, and bleedings were not detected by X-ray examination."} {"id": "PMID:1265433", "title": "Post prandial changes in colonic motility related to serum gastrin levels.", "content": "Colonic motor activity and serum gastrin levels were correlated during a basal period and after a meal in 16 subjects. Motor activity preceded the gastrin response. The motility index and the serum gastrin levels rose in parallel, but the motility fell before later showing a second rise. The frequency response showed the earliest change and since it preceded the gastrin rise may be neurogenic. This response was later \"extinguished\" and replaced by one of waves of increasing amplitude; the sustained nature of this response fitted more closely the gastrin response.", "contents": "Post prandial changes in colonic motility related to serum gastrin levels. Colonic motor activity and serum gastrin levels were correlated during a basal period and after a meal in 16 subjects. Motor activity preceded the gastrin response. The motility index and the serum gastrin levels rose in parallel, but the motility fell before later showing a second rise. The frequency response showed the earliest change and since it preceded the gastrin rise may be neurogenic. This response was later \"extinguished\" and replaced by one of waves of increasing amplitude; the sustained nature of this response fitted more closely the gastrin response."} {"id": "PMID:1265434", "title": "Gastric emptying and bile acid concentration in the duodenum after bypass operation of the small intestine because of obesity.", "content": "Gastric emptying was measured concomitantly with bile acid concentration in the duodenum in 9 patients operated upon with jejuno-ileal bypass. Two of them were cholecystectomized. The results of gastric emptying were compared with those of 7 healthy volunteers. The emptying rate was within normal limits, except for one cholecystectomized shunt-operated patient who had extremely low bile acid concentration in the duodenum.", "contents": "Gastric emptying and bile acid concentration in the duodenum after bypass operation of the small intestine because of obesity. Gastric emptying was measured concomitantly with bile acid concentration in the duodenum in 9 patients operated upon with jejuno-ileal bypass. Two of them were cholecystectomized. The results of gastric emptying were compared with those of 7 healthy volunteers. The emptying rate was within normal limits, except for one cholecystectomized shunt-operated patient who had extremely low bile acid concentration in the duodenum."} {"id": "PMID:1265435", "title": "Morphometric studies of the small intestine following jejuno-ileal shunt operation.", "content": "In five patients in whom a jejuno-ileal by-pass had been previously performed for massive obesity, a relaparotomy was performed because of subjective complaints or unsatisfactory weight reduction. At the reoperation morphometric studies were made of the functioning segments and the by-passed intestine. Length and circumferential measurements were taken, and the villous height and mucosal thickness were measured from histological biopsies. The results were compared with the findings in a control group. After shunt operation adoptive hypertrophy in the functioning remnant, a considerable length growth and dilatation of the gut, as well as a marked increase in villous height and total mucosal thickness, were demonstrated. These adaptive changes seem to be more marked in the distal part of the small intestine. No atrophy of the mucosa could be demonstrated in the excluded intestinal loop.", "contents": "Morphometric studies of the small intestine following jejuno-ileal shunt operation. In five patients in whom a jejuno-ileal by-pass had been previously performed for massive obesity, a relaparotomy was performed because of subjective complaints or unsatisfactory weight reduction. At the reoperation morphometric studies were made of the functioning segments and the by-passed intestine. Length and circumferential measurements were taken, and the villous height and mucosal thickness were measured from histological biopsies. The results were compared with the findings in a control group. After shunt operation adoptive hypertrophy in the functioning remnant, a considerable length growth and dilatation of the gut, as well as a marked increase in villous height and total mucosal thickness, were demonstrated. These adaptive changes seem to be more marked in the distal part of the small intestine. No atrophy of the mucosa could be demonstrated in the excluded intestinal loop."} {"id": "PMID:1265436", "title": "Bile acids in bile during long-term chenodeoxycholic acid treatment.", "content": "Relative concentrations of conjugated and sulfated bile acids in duodenal bile were measured in 5 patients before and during treatment with 0.50-0.75 g of chenodeoxycholic acid per day for 3-4 months. Lithocholic acid constituted 0.8-3.3% (mean 1.8%) of total conjugated and sulfated bile acids before and 0-5.4% (mean 2.6%) during treatment. Lithocholic acid was the predominant bile acid in the sulfate fraction in three patients and chenodeoxycholic acid in two. Sulfated bile acids constituted less than 1% of total bile acids and did not increase during treatment. Ursodeoxycholic acid, the other major metabolite of chenodeoxycholic acid, was found in higher amounts during therapy. The unsaturated bile acid 3beta-hydroxy-delta5-cholenic acid, which was found exclusively as its sulfate ester, showed a slight fall. The average G/T conjugation ratio rose from 2.2 to 4.5.", "contents": "Bile acids in bile during long-term chenodeoxycholic acid treatment. Relative concentrations of conjugated and sulfated bile acids in duodenal bile were measured in 5 patients before and during treatment with 0.50-0.75 g of chenodeoxycholic acid per day for 3-4 months. Lithocholic acid constituted 0.8-3.3% (mean 1.8%) of total conjugated and sulfated bile acids before and 0-5.4% (mean 2.6%) during treatment. Lithocholic acid was the predominant bile acid in the sulfate fraction in three patients and chenodeoxycholic acid in two. Sulfated bile acids constituted less than 1% of total bile acids and did not increase during treatment. Ursodeoxycholic acid, the other major metabolite of chenodeoxycholic acid, was found in higher amounts during therapy. The unsaturated bile acid 3beta-hydroxy-delta5-cholenic acid, which was found exclusively as its sulfate ester, showed a slight fall. The average G/T conjugation ratio rose from 2.2 to 4.5."} {"id": "PMID:1265437", "title": "The effect of carbachol on resting gastro-oesophageal sphincter pressure and serum gastrin in normal human subjects.", "content": "With the purpose of investigating the mechanism of action behind the rise in gastro-oesophageal sphincter pressure induced by cholinergic activity, serum gastrin and sphincter pressure were recorded in 8 normal human subjects before and in relation to administration of carbachol. Carbachol was given subcutaneously in a dose of 4.5 mug per kg body weight. Mean sphincter pressure recorded 15, 30, and 45 minutes after administration of carbachol was significantly higher than the basal mean. The administration of carbachol did not lead to significant changes in serum gastrin and a relationship between serum gastrin and sphincter pressure was not demonstrable. It is concluded, that the carbachol-induced rise in the basal sphincter pressure is not dependent on an increase in serum gastrin, but probably attributable to either direct cholinergic stimulation of the receptors or a cholinergically enhanced sensitivity of the receptors for gastrin. Moreover, it is concluded that carbachol in individual dosages may be a suitable adjuvant in the medical treatment of patients with gastro-oesophageal reflux.", "contents": "The effect of carbachol on resting gastro-oesophageal sphincter pressure and serum gastrin in normal human subjects. With the purpose of investigating the mechanism of action behind the rise in gastro-oesophageal sphincter pressure induced by cholinergic activity, serum gastrin and sphincter pressure were recorded in 8 normal human subjects before and in relation to administration of carbachol. Carbachol was given subcutaneously in a dose of 4.5 mug per kg body weight. Mean sphincter pressure recorded 15, 30, and 45 minutes after administration of carbachol was significantly higher than the basal mean. The administration of carbachol did not lead to significant changes in serum gastrin and a relationship between serum gastrin and sphincter pressure was not demonstrable. It is concluded, that the carbachol-induced rise in the basal sphincter pressure is not dependent on an increase in serum gastrin, but probably attributable to either direct cholinergic stimulation of the receptors or a cholinergically enhanced sensitivity of the receptors for gastrin. Moreover, it is concluded that carbachol in individual dosages may be a suitable adjuvant in the medical treatment of patients with gastro-oesophageal reflux."} {"id": "PMID:1265438", "title": "Serum orosomucoid in ulcerative colitis: its relation to clinical activity, protein loss, and turnover of albumin and IgG.", "content": "Serum orosomucoid was compared with clinical activity, routine laboratory tests, intestinal protein loss, and albumin and IgG turnover in 22 cases of ulcerative colitis. Serum orosomucoid was well correlated with clinical activity, haemoglobin and leucocyte counts were not. A significant correlation was present between serum orosomucoid and intestinal protein loss (gastro-intestinal 59Fe-iron dextran clearance), serum albumin, fractional catabolic rates of albumin, and IgG and IgG synthesis rate. No correlation was found between serum orosomucoid and albumin synthesis rate or serum IgG. It is concluded that serum orosomucoid is a highly reliable indicator of disease activity in ulcerative colitis.", "contents": "Serum orosomucoid in ulcerative colitis: its relation to clinical activity, protein loss, and turnover of albumin and IgG. Serum orosomucoid was compared with clinical activity, routine laboratory tests, intestinal protein loss, and albumin and IgG turnover in 22 cases of ulcerative colitis. Serum orosomucoid was well correlated with clinical activity, haemoglobin and leucocyte counts were not. A significant correlation was present between serum orosomucoid and intestinal protein loss (gastro-intestinal 59Fe-iron dextran clearance), serum albumin, fractional catabolic rates of albumin, and IgG and IgG synthesis rate. No correlation was found between serum orosomucoid and albumin synthesis rate or serum IgG. It is concluded that serum orosomucoid is a highly reliable indicator of disease activity in ulcerative colitis."} {"id": "PMID:1265439", "title": "The long-term prognosis of ileorectal anastomosis and proctocolectomy in Crohn's disease.", "content": "In a series of 226 patients with Crohn's disease admitted to the University Hospital at Leiden between 1934 and 1972, 21 of the 60 patients with almost total colonic involvement were treated by an ileo-rectal anastomosis between 1957 and 1973. Sixteen patients underwent a proctocolectomy between 1948 and 1972. Five of them have previously had an ileo-rectal anastomosis and are therefore included in both groups. The patients have been followed up for a mean period of 8.3 years. There was no surgical mortality in the group of ileo-rectal anastomosis, whereas in the group of proctocolectomy there have been one early and one late postoperative death. The recurrence rate after ileo-rectal anastomosis was 75 per cent, but 40 per cent of these cases responded well to conservative treatment and have not required further surgery. The recurrence rate after proctocolectomy was 31 per cent. The results concerning mortality, morbidity, and recurrence are compared with the series in the literature.", "contents": "The long-term prognosis of ileorectal anastomosis and proctocolectomy in Crohn's disease. In a series of 226 patients with Crohn's disease admitted to the University Hospital at Leiden between 1934 and 1972, 21 of the 60 patients with almost total colonic involvement were treated by an ileo-rectal anastomosis between 1957 and 1973. Sixteen patients underwent a proctocolectomy between 1948 and 1972. Five of them have previously had an ileo-rectal anastomosis and are therefore included in both groups. The patients have been followed up for a mean period of 8.3 years. There was no surgical mortality in the group of ileo-rectal anastomosis, whereas in the group of proctocolectomy there have been one early and one late postoperative death. The recurrence rate after ileo-rectal anastomosis was 75 per cent, but 40 per cent of these cases responded well to conservative treatment and have not required further surgery. The recurrence rate after proctocolectomy was 31 per cent. The results concerning mortality, morbidity, and recurrence are compared with the series in the literature."} {"id": "PMID:1265440", "title": "Nosography of X-ray negative dyspepsia.", "content": "The clinical pictures of 109 patients with X-ray negative dyspepsia (XND) are described, and a comparison is made with the clinical pictures of 39 gastric ulcer patients and 61 duodenal ulcer patients. In addition it has been attempted to subdivide XND into clinically relevant subgroups by means of a Venn diagram. The XND patients were characterized by an equal sex distribution and, in comparison with the ulcer patients, a shorter length of history. The upper abdominal pain was less frequently relieved by eating and more frequently provoked by eating in XND than in ulcer disease. The XND patients also suffered more frequently from irritable colon symptoms. Endoscopy only revealed an ulcer in 11 patients with XND, and the clinical pictures of these patients differed from those of patients with radiologically demonstrated ulcers. The clinical pictures of XND are further analysed in the context of current hypotheses, and it is concluded that Venn diagrams are useful for the analysis of heterogeneous clinical syndromes.", "contents": "Nosography of X-ray negative dyspepsia. The clinical pictures of 109 patients with X-ray negative dyspepsia (XND) are described, and a comparison is made with the clinical pictures of 39 gastric ulcer patients and 61 duodenal ulcer patients. In addition it has been attempted to subdivide XND into clinically relevant subgroups by means of a Venn diagram. The XND patients were characterized by an equal sex distribution and, in comparison with the ulcer patients, a shorter length of history. The upper abdominal pain was less frequently relieved by eating and more frequently provoked by eating in XND than in ulcer disease. The XND patients also suffered more frequently from irritable colon symptoms. Endoscopy only revealed an ulcer in 11 patients with XND, and the clinical pictures of these patients differed from those of patients with radiologically demonstrated ulcers. The clinical pictures of XND are further analysed in the context of current hypotheses, and it is concluded that Venn diagrams are useful for the analysis of heterogeneous clinical syndromes."} {"id": "PMID:1265441", "title": "Gastroduodenal motor response to natural motilin and synthetic position 13-substituted motilin analogues: a comparative in vitro study.", "content": "Motor effects of graded concentrations of pure natural porcine motilin (13-Met-M) and synthetic motilin analogues - the methionine in position 13 substituted with either norleucine (13-Nle-M) or leucine (13-Leu-M) - on the rabbit, guinea-pig, rat, and human gastrointestinal smooth muscle were examined in vitro. Congruent species specificity of the motor activity of the motilins under study could be demonstrated in that muscle strips from rabbit and man were highly sensitive, whereas guinea-pig and rat preparations proved refractory to the polypeptides. In rabbit duodenal muscle and fundic muscle of the human stomach, graded concentrations of 13-Met-M, 13-Nle-M, and 13-Leu-M, respectively, produced graded increases in the contractile responses. The concentration-response curves were superimposable. Calculated maximal contractile responses (CMR's) and polypeptide doses for one-half maximal responses (D50 values) were not significantly different between the three motilins. Moreover, pharmacological analysis revealed that the motor effects of 13-Met-M, 13-Nle-M, and 13-Leu-M are uniformly not mediated via nervous pathways: neither blockage of axonal conduction by tetrodotoxin nor anticholinergic action by atropine exerted any detectable influence. Viewing the data presented, one may conclude that in man and rabbit, 1) natural porcine motilin and its synthetic position 13-substituted analogues, 13-Nle-M and 13-Leu-M, are of equal efficacy for gastroduodenal motor activity, and 2) position 13 of the amino acid sequence of motilin (22-residue chain) is not pertinent to the active site of the molecule.", "contents": "Gastroduodenal motor response to natural motilin and synthetic position 13-substituted motilin analogues: a comparative in vitro study. Motor effects of graded concentrations of pure natural porcine motilin (13-Met-M) and synthetic motilin analogues - the methionine in position 13 substituted with either norleucine (13-Nle-M) or leucine (13-Leu-M) - on the rabbit, guinea-pig, rat, and human gastrointestinal smooth muscle were examined in vitro. Congruent species specificity of the motor activity of the motilins under study could be demonstrated in that muscle strips from rabbit and man were highly sensitive, whereas guinea-pig and rat preparations proved refractory to the polypeptides. In rabbit duodenal muscle and fundic muscle of the human stomach, graded concentrations of 13-Met-M, 13-Nle-M, and 13-Leu-M, respectively, produced graded increases in the contractile responses. The concentration-response curves were superimposable. Calculated maximal contractile responses (CMR's) and polypeptide doses for one-half maximal responses (D50 values) were not significantly different between the three motilins. Moreover, pharmacological analysis revealed that the motor effects of 13-Met-M, 13-Nle-M, and 13-Leu-M are uniformly not mediated via nervous pathways: neither blockage of axonal conduction by tetrodotoxin nor anticholinergic action by atropine exerted any detectable influence. Viewing the data presented, one may conclude that in man and rabbit, 1) natural porcine motilin and its synthetic position 13-substituted analogues, 13-Nle-M and 13-Leu-M, are of equal efficacy for gastroduodenal motor activity, and 2) position 13 of the amino acid sequence of motilin (22-residue chain) is not pertinent to the active site of the molecule."} {"id": "PMID:1265442", "title": "Serum lysozyme in Crohn's disease and ulcerative colitis.", "content": "Serum lysozyme (muramidase) was determined in 72 patients with Crohn's disease or ulcerative colitis. Serum lysozyme was elevated in both disease groups. The mean enzyme level was significantly higher in Crohn's disease than in ulcerative colitis, but there was a considerable overlapping between the groups, which makes serum lysozyme determination of dubious value in the differential diagnosis between Crohn's disease and ulcerative colitis. No correlation was found between the serum lysozyme concentration and the activity of the diseases.", "contents": "Serum lysozyme in Crohn's disease and ulcerative colitis. Serum lysozyme (muramidase) was determined in 72 patients with Crohn's disease or ulcerative colitis. Serum lysozyme was elevated in both disease groups. The mean enzyme level was significantly higher in Crohn's disease than in ulcerative colitis, but there was a considerable overlapping between the groups, which makes serum lysozyme determination of dubious value in the differential diagnosis between Crohn's disease and ulcerative colitis. No correlation was found between the serum lysozyme concentration and the activity of the diseases."} {"id": "PMID:1265443", "title": "Jejunal inhibition of pentagastrin-induced gastric acid secretion in man and Heidenhain pouch dogs.", "content": "The administration of hypertonic glucose and saline and of fat intrajejunally in man caused a marked and almost identical inhibition of pentagastrin-stimulated gastric acid secretion. Hypertonic glucose administered intrajejunally in Heidenhain pouch dogs resulted in an equal inhibition of pentagastrin-induced acid secretion from the pouch and the main stomach, whereas hypertonic saline had no effect. The study demonstrates the existence of potent jejunal inhibitors of gastric secretion, which seem to operate independently of vagal innervation.", "contents": "Jejunal inhibition of pentagastrin-induced gastric acid secretion in man and Heidenhain pouch dogs. The administration of hypertonic glucose and saline and of fat intrajejunally in man caused a marked and almost identical inhibition of pentagastrin-stimulated gastric acid secretion. Hypertonic glucose administered intrajejunally in Heidenhain pouch dogs resulted in an equal inhibition of pentagastrin-induced acid secretion from the pouch and the main stomach, whereas hypertonic saline had no effect. The study demonstrates the existence of potent jejunal inhibitors of gastric secretion, which seem to operate independently of vagal innervation."} {"id": "PMID:1265444", "title": "Estimation of aggregates of IgG and their effect on quantitation of IgG. I. A comparison of four quantitating methods.", "content": "Four quantitating techniques - radial immunodiffusion (RID),electroimmunoassay (EIA), thin-layer Sephadex gel filtration (GF), and GF with an added, specific immunoprecipitation step, immuno-gel filtration (IGF) - are compared for their accuracy in quantitating IgG of various molecular sizes - that is, pure 7S IgG and aggregated IgG, from large polymers to dimeric 10S molecular size. The aggregate fractions differed and were stable with regard to their migration in thin-layer gel filtration, their electromobility in agar and agarose, and their diffusibility in agarose. All four methods quantitated the largest aggregates four to five-fold lower and the next largest at no better than half the Lowry ratings. Only GF and IGF quantitated the two fractions of smaller aggregates within 10% of the expected value. The presence of about 50% of the two larger aggregates in prepared mixes with 7S IgG reduced quantitation results by about half to two thirds with all four methods; the smaller aggregates at 50% concentration were estimated within 16% of the correct values. Twenty percent aggragated IgG about the mean amount found in commercial gamma-globulin preparations, influenced measurments with RID, GF and IGF by less than 10% and the results with EIA by less than 16%.", "contents": "Estimation of aggregates of IgG and their effect on quantitation of IgG. I. A comparison of four quantitating methods. Four quantitating techniques - radial immunodiffusion (RID),electroimmunoassay (EIA), thin-layer Sephadex gel filtration (GF), and GF with an added, specific immunoprecipitation step, immuno-gel filtration (IGF) - are compared for their accuracy in quantitating IgG of various molecular sizes - that is, pure 7S IgG and aggregated IgG, from large polymers to dimeric 10S molecular size. The aggregate fractions differed and were stable with regard to their migration in thin-layer gel filtration, their electromobility in agar and agarose, and their diffusibility in agarose. All four methods quantitated the largest aggregates four to five-fold lower and the next largest at no better than half the Lowry ratings. Only GF and IGF quantitated the two fractions of smaller aggregates within 10% of the expected value. The presence of about 50% of the two larger aggregates in prepared mixes with 7S IgG reduced quantitation results by about half to two thirds with all four methods; the smaller aggregates at 50% concentration were estimated within 16% of the correct values. Twenty percent aggragated IgG about the mean amount found in commercial gamma-globulin preparations, influenced measurments with RID, GF and IGF by less than 10% and the results with EIA by less than 16%."} {"id": "PMID:1265445", "title": "Serum creatine phosphokinase in epidemic influenza.", "content": "Creatine phosphokinase (CPK) in serum was determined in the acute stage of 22 patients confined to bed with epidemic influenza and in the covalescence. Further, 21 healthy controls were investigated during bed rest and when ambulant. The activities of CPK were higher in the acute stage of influenza than during the convalescence out of bed, whilst the controls showed higher activities when ambulant than during bed rest. The findings are compatible with involvement of striated muscle in epidemic influenza.", "contents": "Serum creatine phosphokinase in epidemic influenza. Creatine phosphokinase (CPK) in serum was determined in the acute stage of 22 patients confined to bed with epidemic influenza and in the covalescence. Further, 21 healthy controls were investigated during bed rest and when ambulant. The activities of CPK were higher in the acute stage of influenza than during the convalescence out of bed, whilst the controls showed higher activities when ambulant than during bed rest. The findings are compatible with involvement of striated muscle in epidemic influenza."} {"id": "PMID:1265446", "title": "Serological studies on Mycoplasma hominis: serotypic distribution of recent clinical isolates.", "content": "Serotyping of strains of Mycoplasma hominis, freshly isolated from various sources, was conducted using the complement-independent growth agglutination (GA) test, using the 7 reference antisera prepared in our laboratory. Multiple isolates from a common source indicated that only a single serotype tends to be found, making it possible to serotype clinical isolates without further cloning. However, cultures collected at different times from the same individual may contain different serotypes. A total of 213 recent cultures were serotyping and a majority of these were assigned to the closely related serogroups 1, 2, and 3. Strains isolated during pregnancy, that were associated with various disorders of pregnancy, were serotypically diverse and no one strain seemed to be particularly likely to be associated with disorders of pregnancy.", "contents": "Serological studies on Mycoplasma hominis: serotypic distribution of recent clinical isolates. Serotyping of strains of Mycoplasma hominis, freshly isolated from various sources, was conducted using the complement-independent growth agglutination (GA) test, using the 7 reference antisera prepared in our laboratory. Multiple isolates from a common source indicated that only a single serotype tends to be found, making it possible to serotype clinical isolates without further cloning. However, cultures collected at different times from the same individual may contain different serotypes. A total of 213 recent cultures were serotyping and a majority of these were assigned to the closely related serogroups 1, 2, and 3. Strains isolated during pregnancy, that were associated with various disorders of pregnancy, were serotypically diverse and no one strain seemed to be particularly likely to be associated with disorders of pregnancy."} {"id": "PMID:1265447", "title": "Two fatal cases of meningoencephalitis associated with Mycoplasma pneumoniae infection.", "content": "Two fatal cases of meningoencephalitis with serological indication of Mycoplasma pneumoniae infection are reported. The patients were young boys, 13 and 17 years old. Attention is drawn to the risk of sequelae or of a fatal outcome in patients where this infection is associated with symptoms from the central nervous system.", "contents": "Two fatal cases of meningoencephalitis associated with Mycoplasma pneumoniae infection. Two fatal cases of meningoencephalitis with serological indication of Mycoplasma pneumoniae infection are reported. The patients were young boys, 13 and 17 years old. Attention is drawn to the risk of sequelae or of a fatal outcome in patients where this infection is associated with symptoms from the central nervous system."} {"id": "PMID:1265448", "title": "Mitogen stimulation of lymphocytes from patients with epidemic influenza.", "content": "The in vitro responses to PHA (phytohemagglutinin) of lymphocytes from 14 patients with influenza A and 4 patients with influenza B infection were found decreased as compared with the responses to the same mitogen demonstrated in lymphocytes obtained from the same patients after recovery. Lymphocytes from 6 of the patients with influenza A were examined for PWM (pokeweed mitogen) stimulability and a decrease was found during the influenza infection. The decrease of PHA response during the acute stage of the disease was observed in the presence of autologous as well as of fetal calf and allogeneic AB serum. Possible mechanisms causing this impaired function of lymphocytes are discussed.", "contents": "Mitogen stimulation of lymphocytes from patients with epidemic influenza. The in vitro responses to PHA (phytohemagglutinin) of lymphocytes from 14 patients with influenza A and 4 patients with influenza B infection were found decreased as compared with the responses to the same mitogen demonstrated in lymphocytes obtained from the same patients after recovery. Lymphocytes from 6 of the patients with influenza A were examined for PWM (pokeweed mitogen) stimulability and a decrease was found during the influenza infection. The decrease of PHA response during the acute stage of the disease was observed in the presence of autologous as well as of fetal calf and allogeneic AB serum. Possible mechanisms causing this impaired function of lymphocytes are discussed."} {"id": "PMID:1265452", "title": "[Pathophysiology and diagnosis of bradyarrhythmias in sick sinus syndrome].", "content": "The sick sinus syndrome (SSS) is a complex cardiac disturbance involving impulse formation and conduction. Anatomy and physiology of the sinus node and atrial conduction are reviewed and the pathophysiology of bradycardia and tachycardia in the SSS is discussed. Finally, a practical approach to diagnosis is outlined.", "contents": "[Pathophysiology and diagnosis of bradyarrhythmias in sick sinus syndrome]. The sick sinus syndrome (SSS) is a complex cardiac disturbance involving impulse formation and conduction. Anatomy and physiology of the sinus node and atrial conduction are reviewed and the pathophysiology of bradycardia and tachycardia in the SSS is discussed. Finally, a practical approach to diagnosis is outlined."} {"id": "PMID:1265453", "title": "[Additional pacemaker indications].", "content": "In addition to the widely accepted criteria for the implantation of a permanent pacemaker (bradyarrhythmias combined with syncope, cardiac decompensation, angina pectoris etc.) ther are borderline situations where the decision for a pacemaker is less easy: 1) marked bradycardia with only minor symptoms, 2) syncope without appropriate electrocardiographic abnormality, 3) bifascicular blocks, 4) tachyarrhythmias refractory to medical therapy. In connection with these situations, 3 syndromes are discussed with particular reference to the indication for pacemaker: A) hyperactive carotid sinus reflex syndrome, B) sick sinus syndrome, C) fascicular block. A pacemaker is a fairly safe method of therapy (although with some complications) which should not only be used as a last resort (e.g. in severe Adams-Stokes syndrome) but in patients whose condition may improve after a pacemaker implantation or be prevented from getting worse. Patients with pacemakers have a mean survival rate of 80-90% after 1 year and of 50-60% after 5 years.", "contents": "[Additional pacemaker indications]. In addition to the widely accepted criteria for the implantation of a permanent pacemaker (bradyarrhythmias combined with syncope, cardiac decompensation, angina pectoris etc.) ther are borderline situations where the decision for a pacemaker is less easy: 1) marked bradycardia with only minor symptoms, 2) syncope without appropriate electrocardiographic abnormality, 3) bifascicular blocks, 4) tachyarrhythmias refractory to medical therapy. In connection with these situations, 3 syndromes are discussed with particular reference to the indication for pacemaker: A) hyperactive carotid sinus reflex syndrome, B) sick sinus syndrome, C) fascicular block. A pacemaker is a fairly safe method of therapy (although with some complications) which should not only be used as a last resort (e.g. in severe Adams-Stokes syndrome) but in patients whose condition may improve after a pacemaker implantation or be prevented from getting worse. Patients with pacemakers have a mean survival rate of 80-90% after 1 year and of 50-60% after 5 years."} {"id": "PMID:1265454", "title": "[Heart disease and pregnancy].", "content": "The normal cardiovascular adjustments to pregnancy and the hemodynamic disorders attendant on various acquired and congenital cardiac defects is pregnancy are reviewed. The incidence of the various cardiovascular complications during pregnancy is discussed in relation to each individual type of heart disease. The modern diagnostic and therapeutic possibilities offered by cardiology mean that an increasing number of patients with cardiac defects can look forward to safe pregnancy and childbirth.", "contents": "[Heart disease and pregnancy]. The normal cardiovascular adjustments to pregnancy and the hemodynamic disorders attendant on various acquired and congenital cardiac defects is pregnancy are reviewed. The incidence of the various cardiovascular complications during pregnancy is discussed in relation to each individual type of heart disease. The modern diagnostic and therapeutic possibilities offered by cardiology mean that an increasing number of patients with cardiac defects can look forward to safe pregnancy and childbirth."} {"id": "PMID:1265455", "title": "[Primary and secondary Raynaud's syndrome].", "content": "In the light of practical considerations a distinction is necessary between vasospastic and occlusive disease of hand and finger arteries. The vasospastic condition is usually termed Raynaud's disease and leads to recurrent ischemic attacks affecting the fingers, with early onset in life. In most instances, organic occlusions of peripheral arteries develop without initial vasospastic symptoms (exception: patients with collagen vascular disorders). Measurements of finger blood flow reported in this review show that vasospastic Raynaud's disease may be considered a variant of physiologic flow behavior in young women. Only in severe cases do cold stimuli precipitate long-lasting periods of non-measurable finger flow (venous occlusion plethysmography with finger strain gauges). In 109 personal observations the possible etiologic factors involved in organic finger artery occlusions are analyzed. They include a broad spectrum (arteriosclerosis obliterans, endangitis obliterans, collagen vascular disease, thrombocytosis, chronic occupational trauma, cryoglobulinemia). Therapy is directed at the underlying disease and the specific situation. In cases with severe ischemic symptoms, sympathectomy, intraarterial injections of reserpine, and treatment with Ancrod or fibrinolytic agents should be considered.", "contents": "[Primary and secondary Raynaud's syndrome]. In the light of practical considerations a distinction is necessary between vasospastic and occlusive disease of hand and finger arteries. The vasospastic condition is usually termed Raynaud's disease and leads to recurrent ischemic attacks affecting the fingers, with early onset in life. In most instances, organic occlusions of peripheral arteries develop without initial vasospastic symptoms (exception: patients with collagen vascular disorders). Measurements of finger blood flow reported in this review show that vasospastic Raynaud's disease may be considered a variant of physiologic flow behavior in young women. Only in severe cases do cold stimuli precipitate long-lasting periods of non-measurable finger flow (venous occlusion plethysmography with finger strain gauges). In 109 personal observations the possible etiologic factors involved in organic finger artery occlusions are analyzed. They include a broad spectrum (arteriosclerosis obliterans, endangitis obliterans, collagen vascular disease, thrombocytosis, chronic occupational trauma, cryoglobulinemia). Therapy is directed at the underlying disease and the specific situation. In cases with severe ischemic symptoms, sympathectomy, intraarterial injections of reserpine, and treatment with Ancrod or fibrinolytic agents should be considered."} {"id": "PMID:1265456", "title": "[Experiences with Dotter's percutaneous recanalization of chronic arterial occlusions].", "content": "Since 1971 141 patients (mean age 66 years, range 46-85 years) with chronic occlusions of the pelvic (19) and superficial femoral popliteal arteries (122) have been treated by the percutaneous recanalization technique first described by Dotter and Judkins in 1964. Since 1974 we have employed a modification of the original Dotter technique. The occluding material is removed with a double-lumen distensible catheter introduced over a guide wire. Primary success was achieved in 117 (83%) patients. Re-occlusions occurred in 18 patients after 6 months and in 5 patients in the second half of the first year, giving an overall patency rate of 75%. Up to now no further re-occlusions of dilated arterial segments have been observed. Indications for this treatment as compared with vascular surgery are discussed.", "contents": "[Experiences with Dotter's percutaneous recanalization of chronic arterial occlusions]. Since 1971 141 patients (mean age 66 years, range 46-85 years) with chronic occlusions of the pelvic (19) and superficial femoral popliteal arteries (122) have been treated by the percutaneous recanalization technique first described by Dotter and Judkins in 1964. Since 1974 we have employed a modification of the original Dotter technique. The occluding material is removed with a double-lumen distensible catheter introduced over a guide wire. Primary success was achieved in 117 (83%) patients. Re-occlusions occurred in 18 patients after 6 months and in 5 patients in the second half of the first year, giving an overall patency rate of 75%. Up to now no further re-occlusions of dilated arterial segments have been observed. Indications for this treatment as compared with vascular surgery are discussed."} {"id": "PMID:1265457", "title": "[Drug interactions].", "content": "Beneficial and adverse interactions between drugs may occur in connection with any process that influences the pharmacokinetic and pharmacodynamic behaviour of a given drug and thus affects its therapeutic or toxic action. In dealing with drug interactions and their consequences, a uniform mode of classifying and reporting drug interactions based on clinical relevance appears to be needful.", "contents": "[Drug interactions]. Beneficial and adverse interactions between drugs may occur in connection with any process that influences the pharmacokinetic and pharmacodynamic behaviour of a given drug and thus affects its therapeutic or toxic action. In dealing with drug interactions and their consequences, a uniform mode of classifying and reporting drug interactions based on clinical relevance appears to be needful."} {"id": "PMID:1265458", "title": "[The heart in myasthenia gravis. Electrocardiographic, cardiodynamic and kinetocardiographic aspects in 18 cases].", "content": "Eighteen patients with myasthenia gravis, second-stage (A or B) according to Ossermann and Genkins, and of young age, were examined as outpatients from the cardiological point of view. Clinical and radiological examination of the heart and large vessels revealed no pathological features. Electrocardiographic abnormalities (including one case of ventricular preexcitation syndrome and one of subepicardial ischemia) were detected in three patients (16,6%). Among the various left ventricular systolic time intervals, only the deformation time was somewhat off normal limits in some cases, but the difference was not statistically significant. In over one-third of the cases, conversely, the kinetocardiogram revealed paradoxical systolic outward movements, indicative of myocardial dyskinesis or dissinergy. The essential normality of systolic time intervals in the presence of manifest abnormalities of the kinetocardiographic curve may be explained by the smallness of hypokinetic or dyskinetic areas, whereby the ejection fraction was not reduced. In general, the ECG and kinetocardiographic tracings showed no tendency to change under the effect of orally administered pyridostigmine.", "contents": "[The heart in myasthenia gravis. Electrocardiographic, cardiodynamic and kinetocardiographic aspects in 18 cases]. Eighteen patients with myasthenia gravis, second-stage (A or B) according to Ossermann and Genkins, and of young age, were examined as outpatients from the cardiological point of view. Clinical and radiological examination of the heart and large vessels revealed no pathological features. Electrocardiographic abnormalities (including one case of ventricular preexcitation syndrome and one of subepicardial ischemia) were detected in three patients (16,6%). Among the various left ventricular systolic time intervals, only the deformation time was somewhat off normal limits in some cases, but the difference was not statistically significant. In over one-third of the cases, conversely, the kinetocardiogram revealed paradoxical systolic outward movements, indicative of myocardial dyskinesis or dissinergy. The essential normality of systolic time intervals in the presence of manifest abnormalities of the kinetocardiographic curve may be explained by the smallness of hypokinetic or dyskinetic areas, whereby the ejection fraction was not reduced. In general, the ECG and kinetocardiographic tracings showed no tendency to change under the effect of orally administered pyridostigmine."} {"id": "PMID:1265459", "title": "[Aminoglycoside antibiotics from a clinical viewpoint].", "content": "Indications, side effects, dosage and pharmacokinetic properties of gentamicin, tobramycin, sisomicin, kanamycin and amikacin are reviewed. Different aspects of aminoglycoside antibiotics in combination with beta-lactam antibiotics are briefly discussed. Finally, the indications for the assay of serum levels of aminoglycosides are listed. Gentamicin, tobramycin and sisomicin appear to be very similar with regard to in vitro performance, clinical efficacy and pharmacology. Ototoxic and nephrotoxic side effects are observed - in decreasing order of frequency - with sisomicin, gentamicin and tobramycin. The advantage of amikacin is its stability against enzymatic inactivation, which should make it an agent of first choice against aminoglycoside-resistant gram-negative bacteria.", "contents": "[Aminoglycoside antibiotics from a clinical viewpoint]. Indications, side effects, dosage and pharmacokinetic properties of gentamicin, tobramycin, sisomicin, kanamycin and amikacin are reviewed. Different aspects of aminoglycoside antibiotics in combination with beta-lactam antibiotics are briefly discussed. Finally, the indications for the assay of serum levels of aminoglycosides are listed. Gentamicin, tobramycin and sisomicin appear to be very similar with regard to in vitro performance, clinical efficacy and pharmacology. Ototoxic and nephrotoxic side effects are observed - in decreasing order of frequency - with sisomicin, gentamicin and tobramycin. The advantage of amikacin is its stability against enzymatic inactivation, which should make it an agent of first choice against aminoglycoside-resistant gram-negative bacteria."} {"id": "PMID:1265460", "title": "[Therapeutic use of antimycotic substances].", "content": "Since secondary deep mycoses are frequently seen in internal medicine nowadays, increasing interest has been focused on antimycotic therapy. This report deals with the limited available range of antimycotic substances which can be administered systemically. Since severe adverse effects are often observed with Amphotericin-B, the most effective antifungal agent, the advent of three new systemic antifungal drugs (Clotrimazole, Miconazole, 5-Fluorocytosine) has proven to be a real advance in our therapeutic approach to deep mycoses. To avoid unwanted side-effects, combined therapy with low doses of Amphotericin-B and another antimycotic agent promises to become increasingly important.", "contents": "[Therapeutic use of antimycotic substances]. Since secondary deep mycoses are frequently seen in internal medicine nowadays, increasing interest has been focused on antimycotic therapy. This report deals with the limited available range of antimycotic substances which can be administered systemically. Since severe adverse effects are often observed with Amphotericin-B, the most effective antifungal agent, the advent of three new systemic antifungal drugs (Clotrimazole, Miconazole, 5-Fluorocytosine) has proven to be a real advance in our therapeutic approach to deep mycoses. To avoid unwanted side-effects, combined therapy with low doses of Amphotericin-B and another antimycotic agent promises to become increasingly important."} {"id": "PMID:1265461", "title": "[Lung biopsy in interstitial pulmonary processes].", "content": "The value of open lung biopsies for the diagnosis of diffuse interstitial lung fibrosis is discussed. Except for few cases, e.g. granulomatous processes, needle biopsies are not a reliable method. In diffuse lung fibroses of unknown etiology which are not related to systemic diseases such as collagen diseases, combined electronmicroscopy and EDAX (Energy Dispersive X-ray Analysis) may reveal pneumoconiotic lesions due to unperceived mineral-dust exposure.", "contents": "[Lung biopsy in interstitial pulmonary processes]. The value of open lung biopsies for the diagnosis of diffuse interstitial lung fibrosis is discussed. Except for few cases, e.g. granulomatous processes, needle biopsies are not a reliable method. In diffuse lung fibroses of unknown etiology which are not related to systemic diseases such as collagen diseases, combined electronmicroscopy and EDAX (Energy Dispersive X-ray Analysis) may reveal pneumoconiotic lesions due to unperceived mineral-dust exposure."} {"id": "PMID:1265462", "title": "[Lung biopsy in interstitial pulmonary processes].", "content": "The techniques for lung biopsy are briefly described. In diffuse interstitial lung disease only open lung biopsy provides sufficient material for histological examination. In view of the severity of this diagnostic intervention the indication must be established restrictively: before biopsy it is essential to rule out all systemic diseases which may also produce interstitial lung disease. Furthermore, open lung biopsy should be considered only if a therapeutic prospect exists.", "contents": "[Lung biopsy in interstitial pulmonary processes]. The techniques for lung biopsy are briefly described. In diffuse interstitial lung disease only open lung biopsy provides sufficient material for histological examination. In view of the severity of this diagnostic intervention the indication must be established restrictively: before biopsy it is essential to rule out all systemic diseases which may also produce interstitial lung disease. Furthermore, open lung biopsy should be considered only if a therapeutic prospect exists."} {"id": "PMID:1265463", "title": "[Primary aldosteronism].", "content": "The syndrome of primary aldosteronism is caused either by an aldosterone-producing adenoma or by idiopathic bilateral adrenal hyperplasia. Hypokalemic hypertension is the leading symptome of the disease. Diagnosis is by the combination of abnormally high and non-suppressible aldosterone values with undetectable or low renin values unresponsive to postural changes or salt restriction. Patients with aldosterone-producing adenoma normally show a fall in plasma aldosterone in response to posture and ACTH-dependent circadian rhythm of aldosterone, whereas bilateral hyperplasia is characterized by postural increases in plasma aldosterone and an ACTH-independent diurnal aldosterone rhythm. These creteria serve to differentiate between adenoma and hyperplasia. An aldosterone-producing adenoma can be localized by veinography, determination of aldosterone concentration in both adrenal veins and by 131I-cholesterol scintigraphy. In our hands the determination of aldosterone in blood from both adrenal veins is the most efficient procedure. In interpreting the results, however, rhythmic and sudden changes in adrenal hormone secretion should be considered. In cases where no adrenal venous blood is obtained, 131I-cholesterol scintigraphy may be used to localize adenoma. In patients with aldosterone-producing adenomas unilateral adrenalectomy should be performed, whereas patients with idiopathic bilateral hyperplasia should receive antihypertensive therapy. As rare instances of primary aldosteronism, a case of aldosterone-producing carcinoma of the adrenal cortex and a case of presumably unilateral adrenal hyperplasia are reported.", "contents": "[Primary aldosteronism]. The syndrome of primary aldosteronism is caused either by an aldosterone-producing adenoma or by idiopathic bilateral adrenal hyperplasia. Hypokalemic hypertension is the leading symptome of the disease. Diagnosis is by the combination of abnormally high and non-suppressible aldosterone values with undetectable or low renin values unresponsive to postural changes or salt restriction. Patients with aldosterone-producing adenoma normally show a fall in plasma aldosterone in response to posture and ACTH-dependent circadian rhythm of aldosterone, whereas bilateral hyperplasia is characterized by postural increases in plasma aldosterone and an ACTH-independent diurnal aldosterone rhythm. These creteria serve to differentiate between adenoma and hyperplasia. An aldosterone-producing adenoma can be localized by veinography, determination of aldosterone concentration in both adrenal veins and by 131I-cholesterol scintigraphy. In our hands the determination of aldosterone in blood from both adrenal veins is the most efficient procedure. In interpreting the results, however, rhythmic and sudden changes in adrenal hormone secretion should be considered. In cases where no adrenal venous blood is obtained, 131I-cholesterol scintigraphy may be used to localize adenoma. In patients with aldosterone-producing adenomas unilateral adrenalectomy should be performed, whereas patients with idiopathic bilateral hyperplasia should receive antihypertensive therapy. As rare instances of primary aldosteronism, a case of aldosterone-producing carcinoma of the adrenal cortex and a case of presumably unilateral adrenal hyperplasia are reported."} {"id": "PMID:1265464", "title": "[Diagnosis and quick diagnosis of breast neoplasms by means of fine needle puncture biopsy].", "content": "The technic, advantages and limitations of the fine needle method for diagnostic purposes in pathologic alterations of the breast are discussed. Our own results bear out the value of the method for rapid diagnosis: puncture of 252 breast tumors and 78 mastectomy scars revealed 37 and 41 suspect or malignant alterations respectively. No false positive diagnoses were recorded. The rate of false negative results was 7.3% in breast tumors and 9.9% in mastectomy scars.", "contents": "[Diagnosis and quick diagnosis of breast neoplasms by means of fine needle puncture biopsy]. The technic, advantages and limitations of the fine needle method for diagnostic purposes in pathologic alterations of the breast are discussed. Our own results bear out the value of the method for rapid diagnosis: puncture of 252 breast tumors and 78 mastectomy scars revealed 37 and 41 suspect or malignant alterations respectively. No false positive diagnoses were recorded. The rate of false negative results was 7.3% in breast tumors and 9.9% in mastectomy scars."} {"id": "PMID:1265465", "title": "[Diagnostic methods for the exploration of the female breast].", "content": "The diagnostic methods for exploration of the female breast (self-examination, clinical examination, mammography, xero-radiography, thermography, open biopsy, and aspiration biopsy smears) are briefly discussed. Their advantages and disadvantages emerge in their application for the detection of breast disease.", "contents": "[Diagnostic methods for the exploration of the female breast]. The diagnostic methods for exploration of the female breast (self-examination, clinical examination, mammography, xero-radiography, thermography, open biopsy, and aspiration biopsy smears) are briefly discussed. Their advantages and disadvantages emerge in their application for the detection of breast disease."} {"id": "PMID:1265466", "title": "[Directions for mammography from a radiological viewpoint].", "content": "A significant decrease in mortality due to breast cancer is feasible only by earlier diagnosis. The decisive screening method is mammography, which permits identification of a malignancy in its earliest stages. Indirect and direct signs of malignancy exist whose detection necessitates biopsy. Radiological examination of the tissue sample permits evaluation of the adequacy of excision and thus renders possible specific histological examination of the region of interest. Pneumocystography is a method for simultaneous diagnosis and therapy of benign cysts.", "contents": "[Directions for mammography from a radiological viewpoint]. A significant decrease in mortality due to breast cancer is feasible only by earlier diagnosis. The decisive screening method is mammography, which permits identification of a malignancy in its earliest stages. Indirect and direct signs of malignancy exist whose detection necessitates biopsy. Radiological examination of the tissue sample permits evaluation of the adequacy of excision and thus renders possible specific histological examination of the region of interest. Pneumocystography is a method for simultaneous diagnosis and therapy of benign cysts."} {"id": "PMID:1265467", "title": "[Which uric acid value is in need of treatment?].", "content": "Asymptomatic hyperuricemia should be treated only if the plasma uric acid levels are around 10 mg/100 ml or more on several determinations. In addition, patients on a purine-free diet who excrete more than 600 mg uric acid per 24 h should be treated. In both cases, treatment is intended to be prophylactic against gouty nephropathy. At present there is no evidence that primary hyperuricemia alone is a risk factor for early atherosclerosis and especially coronary artery disease. However, more attention should be paid to the accompanying risk factors such as obesity, hyperlipoproteinemia, diabetes mellitus and hypertension.", "contents": "[Which uric acid value is in need of treatment?]. Asymptomatic hyperuricemia should be treated only if the plasma uric acid levels are around 10 mg/100 ml or more on several determinations. In addition, patients on a purine-free diet who excrete more than 600 mg uric acid per 24 h should be treated. In both cases, treatment is intended to be prophylactic against gouty nephropathy. At present there is no evidence that primary hyperuricemia alone is a risk factor for early atherosclerosis and especially coronary artery disease. However, more attention should be paid to the accompanying risk factors such as obesity, hyperlipoproteinemia, diabetes mellitus and hypertension."} {"id": "PMID:1265470", "title": "Non-organ specific autoantibodies in malignant diseases.", "content": "A significant increase in non-organ specific autoantibodies is demonstrated in13 per cent of the sera from 202 patients with histologically proven malignancies, as compared with only 4 per cent of sera from 214 age and sex matched control patients. It appears that the incidence of autoantibodies is related to the histological type of the tumour but not to the presence or absence of tumour dissenmination. While the control group shows the expected increase in both incidence and titre of autoantibodies with increasing age, the malignant patients show no such pattern i.e. in cancer patients autoantibodies occur with equal frequency and at similar titres regardless of age. The absence of an age related increase in incidence and titre of non organ specific autoantibodies does not appear to have been reported previously. Our findings lend support to the hypothesis that cancer is associated with a breakdown of immunological surveillance, not only in old but also in young cancer patients. Thus the findings of non organ specific autoantibodies, especially to smooth muscle antigen, in an apparently healthy adult could be considered evidence of such a breakdown, carrying with it an increased risk of neoplasia.", "contents": "Non-organ specific autoantibodies in malignant diseases. A significant increase in non-organ specific autoantibodies is demonstrated in13 per cent of the sera from 202 patients with histologically proven malignancies, as compared with only 4 per cent of sera from 214 age and sex matched control patients. It appears that the incidence of autoantibodies is related to the histological type of the tumour but not to the presence or absence of tumour dissenmination. While the control group shows the expected increase in both incidence and titre of autoantibodies with increasing age, the malignant patients show no such pattern i.e. in cancer patients autoantibodies occur with equal frequency and at similar titres regardless of age. The absence of an age related increase in incidence and titre of non organ specific autoantibodies does not appear to have been reported previously. Our findings lend support to the hypothesis that cancer is associated with a breakdown of immunological surveillance, not only in old but also in young cancer patients. Thus the findings of non organ specific autoantibodies, especially to smooth muscle antigen, in an apparently healthy adult could be considered evidence of such a breakdown, carrying with it an increased risk of neoplasia."} {"id": "PMID:1265471", "title": "Clinical bacteriology of cephazolin.", "content": "Cephazolin, the latest parenteral cephalosporin produced by substitution of heterocyclic groups on the 7-aminocephalosporanic acid (7-ACA) nucleus, became available for clinical use in the U.K. in 1974. Its history is traced from the original Sardinian mould (1945) through isolation of cephalosporin C (1953) and 7-ACA (1962) to its discovery (1969) and subsequent clinical use. Its mode of actionis examined and its bactericidal nature confirmed, MICs of over 500 common pathogens are used to define its spectrum. The cut-off point for sensitivity and resistance is taken as 20 mg. per l. With 30 mug. discs zone sizes less than or equal to 14mm. indicate resistance. The clinical relevance of MICs and attainable serum and urine levels is examined by relating them to clinical response in 12 patients. A disc study compares cephazolin with 4 other available cephalosporins, namely cephaloridine, cephalothinm cephalexin and cephradine. Many major discrepancies indicate that they are not interchangeable. The laboratory and clinical implications are discussed, including the need for local policy decisions regarding choice of preparation. The change from a parenteral to an oral form should be preceded by a sensitivity test against the causal organism. The validity of using a single representative disc is questioned and the use of phrases such as 'sensitive to the cephalosporins' deprecated. Cephazolin is potent, broad-spectrum and bactericidal and is potentially life-saving in serious hospital infections. The cephalosporins rival the aminoglycosides as 'best-guess' primary choice and are preferable in pregnancy, the puerperium and in pulmonary infections. Within the group cephazolin will seriously challenge or even oust cephaloridine and cephalothin.", "contents": "Clinical bacteriology of cephazolin. Cephazolin, the latest parenteral cephalosporin produced by substitution of heterocyclic groups on the 7-aminocephalosporanic acid (7-ACA) nucleus, became available for clinical use in the U.K. in 1974. Its history is traced from the original Sardinian mould (1945) through isolation of cephalosporin C (1953) and 7-ACA (1962) to its discovery (1969) and subsequent clinical use. Its mode of actionis examined and its bactericidal nature confirmed, MICs of over 500 common pathogens are used to define its spectrum. The cut-off point for sensitivity and resistance is taken as 20 mg. per l. With 30 mug. discs zone sizes less than or equal to 14mm. indicate resistance. The clinical relevance of MICs and attainable serum and urine levels is examined by relating them to clinical response in 12 patients. A disc study compares cephazolin with 4 other available cephalosporins, namely cephaloridine, cephalothinm cephalexin and cephradine. Many major discrepancies indicate that they are not interchangeable. The laboratory and clinical implications are discussed, including the need for local policy decisions regarding choice of preparation. The change from a parenteral to an oral form should be preceded by a sensitivity test against the causal organism. The validity of using a single representative disc is questioned and the use of phrases such as 'sensitive to the cephalosporins' deprecated. Cephazolin is potent, broad-spectrum and bactericidal and is potentially life-saving in serious hospital infections. The cephalosporins rival the aminoglycosides as 'best-guess' primary choice and are preferable in pregnancy, the puerperium and in pulmonary infections. Within the group cephazolin will seriously challenge or even oust cephaloridine and cephalothin."} {"id": "PMID:1265472", "title": "Activity of cephazolin and other cephalosporins against Bacteroides fragilis.", "content": "The antibiotic sensitivity of 50 strains of Bacteroides fragilis to four cephalosporin compounds, cephazolin, cephaloridine, cephradine and cephalexin is reported. Cephazolin was found to be the most active, 94 per cent of strains being susceptible to blood concentrations achieved on standard dosage, comparative findings with cephaloridine and cephradine were about 50 per cent, and only 22 per cent of strains were inhibited by cephalexin. The importance of infections due to bacteroides is discussed. Although not the treatment of choice, cephazolin, a view of its bacterial activity may be useful alternative for bacteroides infections but clinical trials are needed to confirm the laboratory results.", "contents": "Activity of cephazolin and other cephalosporins against Bacteroides fragilis. The antibiotic sensitivity of 50 strains of Bacteroides fragilis to four cephalosporin compounds, cephazolin, cephaloridine, cephradine and cephalexin is reported. Cephazolin was found to be the most active, 94 per cent of strains being susceptible to blood concentrations achieved on standard dosage, comparative findings with cephaloridine and cephradine were about 50 per cent, and only 22 per cent of strains were inhibited by cephalexin. The importance of infections due to bacteroides is discussed. Although not the treatment of choice, cephazolin, a view of its bacterial activity may be useful alternative for bacteroides infections but clinical trials are needed to confirm the laboratory results."} {"id": "PMID:1265473", "title": "The serum half-life and urine concentrations of cephazolin sodium in patients with terminal renal failure: effect of haemodialysis.", "content": "The serum and plasma half-life of cephazolin has been determined in 5 maintenance haemodialysis patients during a non-dialysis period and then again in the same patients during haemodialysis with a Meltec Maxi-Multipont dialyser using cuprophance membranes. The mean half-life during the non-dialysis period was 28.3 hours and fell to a mean of 4.97 hours during haemodialysis. Percentage recovery of cephazolin in the urine was markedly reduced in 4 maintenance dialysis patients although adequate urine concentrations of cephazolin were achieved for many sensitive organisms. A dosage schedule for patients with creatinine clearances of less than 5 ml. per minute and for maintenance haemodialysis patients is suggested.", "contents": "The serum half-life and urine concentrations of cephazolin sodium in patients with terminal renal failure: effect of haemodialysis. The serum and plasma half-life of cephazolin has been determined in 5 maintenance haemodialysis patients during a non-dialysis period and then again in the same patients during haemodialysis with a Meltec Maxi-Multipont dialyser using cuprophance membranes. The mean half-life during the non-dialysis period was 28.3 hours and fell to a mean of 4.97 hours during haemodialysis. Percentage recovery of cephazolin in the urine was markedly reduced in 4 maintenance dialysis patients although adequate urine concentrations of cephazolin were achieved for many sensitive organisms. A dosage schedule for patients with creatinine clearances of less than 5 ml. per minute and for maintenance haemodialysis patients is suggested."} {"id": "PMID:1265474", "title": "Cephazolin treatment of pneumococcal pneumonia and urinary tract infections.", "content": "Ten cases of pneumococcal pneumonia were treated with cephazolin 500 mg. q8h for at least 5 days. In every case therapy was accompanied by clinical improvement and eradication of the organism. Ten patients with E. coli bacteriuria (5 symptomatic) were treated with cephazolin 500 mg. q12h for 7 to 10 days. In every case the pathogen was eliminated during therapy but in one case bacteriologic relapse occurred following cessation of therapy. In 10 cases of bacteriuria caused by P. mirabilis, Klebsiella sp, Enterobacter, and Enterococcus, the urine became sterile during treatment, but relapse was common. Initial and final creatinine clearances obtained in 29 patients who received an average of 12.9 g. of cephazolin showed no tendency toward loss of renal function. Serial serum levels of cephazolin were determined following the first 500 mg. dose in 18 patients. The peak serum level occurred at one hour with a serum half life of approximately 2.2 hours. For 13 of these 18 patients serial serum levels were also obtained following the last dose of cephazolin. At this time the mean peak level occurred at 2 hours but again the serum half life was approximately 1.9 hours.", "contents": "Cephazolin treatment of pneumococcal pneumonia and urinary tract infections. Ten cases of pneumococcal pneumonia were treated with cephazolin 500 mg. q8h for at least 5 days. In every case therapy was accompanied by clinical improvement and eradication of the organism. Ten patients with E. coli bacteriuria (5 symptomatic) were treated with cephazolin 500 mg. q12h for 7 to 10 days. In every case the pathogen was eliminated during therapy but in one case bacteriologic relapse occurred following cessation of therapy. In 10 cases of bacteriuria caused by P. mirabilis, Klebsiella sp, Enterobacter, and Enterococcus, the urine became sterile during treatment, but relapse was common. Initial and final creatinine clearances obtained in 29 patients who received an average of 12.9 g. of cephazolin showed no tendency toward loss of renal function. Serial serum levels of cephazolin were determined following the first 500 mg. dose in 18 patients. The peak serum level occurred at one hour with a serum half life of approximately 2.2 hours. For 13 of these 18 patients serial serum levels were also obtained following the last dose of cephazolin. At this time the mean peak level occurred at 2 hours but again the serum half life was approximately 1.9 hours."} {"id": "PMID:1265475", "title": "Comparative biliary concentrations of cephazolin and cephalothin in patients with biliary tract disease.", "content": "The concentration of cephazolin in the serum, gall bladder bile, common duct bile, and gall bladder wall were consideredably higher than cephalothin especially with IV administration and indicate that cephazolin should be a useful antibiotic in the surgical treatment of acute cholecystitis.", "contents": "Comparative biliary concentrations of cephazolin and cephalothin in patients with biliary tract disease. The concentration of cephazolin in the serum, gall bladder bile, common duct bile, and gall bladder wall were consideredably higher than cephalothin especially with IV administration and indicate that cephazolin should be a useful antibiotic in the surgical treatment of acute cholecystitis."} {"id": "PMID:1265476", "title": "Cephazloin sodium - an invivo and in vitro evaluation of 100 patients with urinary tract infections.", "content": "A random group of 100 patients in a general hospital were treated with cephazolin sodium for proven urinary tract infections. Sixty-six per cent had conditions predisposing to urinary tract infection. Under these somewhat difficult conditions the original infecting organism remained absent from the urine of 75 per cent of the 70 patients followed in the 3rd to 6th week period. This compares very favourably with response to other antimicrobial agents currently used in urinary tract infections.", "contents": "Cephazloin sodium - an invivo and in vitro evaluation of 100 patients with urinary tract infections. A random group of 100 patients in a general hospital were treated with cephazolin sodium for proven urinary tract infections. Sixty-six per cent had conditions predisposing to urinary tract infection. Under these somewhat difficult conditions the original infecting organism remained absent from the urine of 75 per cent of the 70 patients followed in the 3rd to 6th week period. This compares very favourably with response to other antimicrobial agents currently used in urinary tract infections."} {"id": "PMID:1265477", "title": "Cephazolin: clinical studies in obstetrics.", "content": "A clinical evaluation of a new cephalosporin, cephazolin, in obstetric patients is presented. Sixteen cardiac patients received the drug prophylactically as antibiotic cover during labour. Eighteen patients with miscellaneous antenatal and puerperal infections received the drug as primary treatment. The data obtained indicate adequate serum and tissue levels with the dose used, and corresponding clinical response. The impression is of a safe and efficaceous drug in the described obstetric situations requiring antibiotic therapy. It may be given prophylactically and with confidence to the cardiac patient in labour.", "contents": "Cephazolin: clinical studies in obstetrics. A clinical evaluation of a new cephalosporin, cephazolin, in obstetric patients is presented. Sixteen cardiac patients received the drug prophylactically as antibiotic cover during labour. Eighteen patients with miscellaneous antenatal and puerperal infections received the drug as primary treatment. The data obtained indicate adequate serum and tissue levels with the dose used, and corresponding clinical response. The impression is of a safe and efficaceous drug in the described obstetric situations requiring antibiotic therapy. It may be given prophylactically and with confidence to the cardiac patient in labour."} {"id": "PMID:1265479", "title": "Gating currents associated with sodium and calcium currents in an Aplysia neuron.", "content": "In a voltage-clamped aplysia neuron (R15), depolarization beyond -30 millivolts produces an inward sodium current. Depolarization beyond -10 millivolts produces an additional inward calcium current with slower kinetics than the sodium current. When these ionic currents have been suppressed and capacitive currents subtracted out, a small outward displacement current can be seen with depolarizations beyond -30 millivolts. An additional, slower displacement current is seen with depolarizations beyond -10 millivolts. The currents have an exponential decay with an increase in rate per 10 degrees C increase in temperature of about 3 and are thought to be sodium and calcium gating currents.", "contents": "Gating currents associated with sodium and calcium currents in an Aplysia neuron. In a voltage-clamped aplysia neuron (R15), depolarization beyond -30 millivolts produces an inward sodium current. Depolarization beyond -10 millivolts produces an additional inward calcium current with slower kinetics than the sodium current. When these ionic currents have been suppressed and capacitive currents subtracted out, a small outward displacement current can be seen with depolarizations beyond -30 millivolts. An additional, slower displacement current is seen with depolarizations beyond -10 millivolts. The currents have an exponential decay with an increase in rate per 10 degrees C increase in temperature of about 3 and are thought to be sodium and calcium gating currents."} {"id": "PMID:1265480", "title": "Uptake of bovine serum albumin by rainbow trout from hypersmotic solutions: a model for vaccinating fish.", "content": "Immersion of juvenile rainbow trout (Salmo gairdneri) in a solution containing either urea or sodium chloride at 1650 milliosmoles and 2 percent of bovine serum albumin (BSA) resulted in an uptake of BSA into the blood of the fish after a 3-minute exposure. Similar blood levels of BSA were also obtained by placing the fish in 1650 millosmoles of sodium chloride for about 2 minutes, and then immersing them in 2 percent BSA solution for 3 minutes. Uptake of BSA into the fish appeared to be primarily through the lateral line system and secondarily through the gills.", "contents": "Uptake of bovine serum albumin by rainbow trout from hypersmotic solutions: a model for vaccinating fish. Immersion of juvenile rainbow trout (Salmo gairdneri) in a solution containing either urea or sodium chloride at 1650 milliosmoles and 2 percent of bovine serum albumin (BSA) resulted in an uptake of BSA into the blood of the fish after a 3-minute exposure. Similar blood levels of BSA were also obtained by placing the fish in 1650 millosmoles of sodium chloride for about 2 minutes, and then immersing them in 2 percent BSA solution for 3 minutes. Uptake of BSA into the fish appeared to be primarily through the lateral line system and secondarily through the gills."} {"id": "PMID:1265481", "title": "Insecticidal action of the phytohemagglutinin in black beans on a bruchid beetle.", "content": "Black bean (Phaseolus vulgaris) phytohemagglutinin added to the normal diet of a bruchid beetle (Callosobruchus maculatus) that can eat phytohemagglutinin-free cowpeas (Vigna unguiculata) but not P. vulgaris seeds kills the bruchid larvae. Trypsin inhibitors, found in both P. vulgaris and V. unguiculata seeds, have virtually no effect on the bruchid larvae. The conclusion is that a major part of the adaptive significance of phytohemagglutinins in black bean and other legume seeds is to protect them from attack by insect seed predators.", "contents": "Insecticidal action of the phytohemagglutinin in black beans on a bruchid beetle. Black bean (Phaseolus vulgaris) phytohemagglutinin added to the normal diet of a bruchid beetle (Callosobruchus maculatus) that can eat phytohemagglutinin-free cowpeas (Vigna unguiculata) but not P. vulgaris seeds kills the bruchid larvae. Trypsin inhibitors, found in both P. vulgaris and V. unguiculata seeds, have virtually no effect on the bruchid larvae. The conclusion is that a major part of the adaptive significance of phytohemagglutinins in black bean and other legume seeds is to protect them from attack by insect seed predators."} {"id": "PMID:1265482", "title": "DNA structure in sheared and unsheared chromatin.", "content": "Shearing chromatin, by either sonication or vortex homogenization, introduces significant structural artifacts. These may be detected by the anomalously large increase in the number of ethidium bromide binding sites and the large alteration of the circular dichroism spectra of chromatin. Structural alterations are also suggested by the disappearance of differential light scattering after shearing.", "contents": "DNA structure in sheared and unsheared chromatin. Shearing chromatin, by either sonication or vortex homogenization, introduces significant structural artifacts. These may be detected by the anomalously large increase in the number of ethidium bromide binding sites and the large alteration of the circular dichroism spectra of chromatin. Structural alterations are also suggested by the disappearance of differential light scattering after shearing."} {"id": "PMID:1265483", "title": "Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras.", "content": "Chimeric rats were produced by the aggregation of embryos of the pinkeyed, retinal dystrophic RCS strain with those of pigmented, normal rats. In the mosaic eyes, patches of neural retina with abnormal and degenerated photoreceptors were present only opposite patches of nonpigmented, mutant pigment epithelium. This indicates that the retinal dystrophy gene acts in the pigment epithelial cell rather than in the photoreceptor cell.", "contents": "Inherited retinal dystrophy: primary defect in pigment epithelium determined with experimental rat chimeras. Chimeric rats were produced by the aggregation of embryos of the pinkeyed, retinal dystrophic RCS strain with those of pigmented, normal rats. In the mosaic eyes, patches of neural retina with abnormal and degenerated photoreceptors were present only opposite patches of nonpigmented, mutant pigment epithelium. This indicates that the retinal dystrophy gene acts in the pigment epithelial cell rather than in the photoreceptor cell."} {"id": "PMID:1265484", "title": "Phytohemagglutinin-induced lymphocyte transformation in humans receiving delta9-tetrahydrocannabinol.", "content": "Eight otherwise healthy male chronic marijuana smokers were hospitalized for a period of 30 days. Initially they received placebo, then a sustained dose of 210 milligrams of delta9-tetrahydrocannabinol (delta9-THC) per day for 18 days, followed by placebo. Lymphocyte responses to phytohemagglutinin were examined during each of these periods. Neither the daily ingestion of marijuana extract containing 210 milligrams of delta9-THC for 18 days nor the history of chronic marijuana smoking had a depressive effect on the lymphocyte responses of these subjects to phytohemagglutinin.", "contents": "Phytohemagglutinin-induced lymphocyte transformation in humans receiving delta9-tetrahydrocannabinol. Eight otherwise healthy male chronic marijuana smokers were hospitalized for a period of 30 days. Initially they received placebo, then a sustained dose of 210 milligrams of delta9-tetrahydrocannabinol (delta9-THC) per day for 18 days, followed by placebo. Lymphocyte responses to phytohemagglutinin were examined during each of these periods. Neither the daily ingestion of marijuana extract containing 210 milligrams of delta9-THC for 18 days nor the history of chronic marijuana smoking had a depressive effect on the lymphocyte responses of these subjects to phytohemagglutinin."} {"id": "PMID:1265491", "title": "Femoral tibial bypass grafts.", "content": "The results of 53 femoral to tibial artery bypass grafts have been reviewed. All were carried out in an attempt to salvage severely ischemic extremities which resulted from arteriosclerotic occlusive disease involving the femoral, popliteal, and tibial arterial systems as demonstrated by arteriography. Most grafts were done with autogenous vein; however, composite grafts comprised of a Dacron prosthesis and an autogenous vein and homologous veins were used in several patients. The initial salvage rate in these pregangrenous extremities was 74%. Fifty-two percent of the grafts remain patent at this writing, a period of 56 months in some instances. This study indicates that most patients with a severely ischemic extremity are candidates for revascularization and should have angiographic studies before amputation is considered.", "contents": "Femoral tibial bypass grafts. The results of 53 femoral to tibial artery bypass grafts have been reviewed. All were carried out in an attempt to salvage severely ischemic extremities which resulted from arteriosclerotic occlusive disease involving the femoral, popliteal, and tibial arterial systems as demonstrated by arteriography. Most grafts were done with autogenous vein; however, composite grafts comprised of a Dacron prosthesis and an autogenous vein and homologous veins were used in several patients. The initial salvage rate in these pregangrenous extremities was 74%. Fifty-two percent of the grafts remain patent at this writing, a period of 56 months in some instances. This study indicates that most patients with a severely ischemic extremity are candidates for revascularization and should have angiographic studies before amputation is considered."} {"id": "PMID:1265492", "title": "The mobile clinic of St. Mary's health center--a functional plan.", "content": "Specialized medical facilities tend to be concentrated in medical centers in metropolitan areas, which results in unavailability of adequate medical care to large portions of our population. One solution is a mobile unit, staffed by personnel representing several different disciplines (physicians, nurses, social workers, nutritionists, etc) and extending a health ministry beyond the confines of a medical center to medically deprived areas. The unit also has educational benefits as the medical and nursing students gain valuable experience by evaluating the patients and relating them to the environment in which they live. The mobile clinic allows for a workable situation in a congenial atmosphere without compromising the quality of health care.", "contents": "The mobile clinic of St. Mary's health center--a functional plan. Specialized medical facilities tend to be concentrated in medical centers in metropolitan areas, which results in unavailability of adequate medical care to large portions of our population. One solution is a mobile unit, staffed by personnel representing several different disciplines (physicians, nurses, social workers, nutritionists, etc) and extending a health ministry beyond the confines of a medical center to medically deprived areas. The unit also has educational benefits as the medical and nursing students gain valuable experience by evaluating the patients and relating them to the environment in which they live. The mobile clinic allows for a workable situation in a congenial atmosphere without compromising the quality of health care."} {"id": "PMID:1265494", "title": "Ferruginous (asbestos) bodies in the lungs of rural dwellers, urban dwellers, and patients with pulmonary neoplasms.", "content": "The lungs of 100 consecutive patients at autopsy and of 24 patients with various pulmonary neoplasms were analyzed for the presence of ferruginous (asbestos) bodies. The population comprised both rural dwellers and urban dwellers, in contrast to previous similar studies involving only urban dwellers. More than 90% of both population groups had ferruginous bodies in their lungs. There was no apparent difference in the incidence or quantity of ferruginous bodies between the group with pulmonary neoplasms and the randomly selected group. These findings raise the possibility of more widespread asbestos dust contamination of environmental air than has been previously thought and indicate that rural as well as urban populations are exposed. The failure to demonstrate more ferruginous bodies in the lungs of patients with pulmonary neoplasms is in accordance with the view that asbestos acts as a cocarcinogen in this regard.", "contents": "Ferruginous (asbestos) bodies in the lungs of rural dwellers, urban dwellers, and patients with pulmonary neoplasms. The lungs of 100 consecutive patients at autopsy and of 24 patients with various pulmonary neoplasms were analyzed for the presence of ferruginous (asbestos) bodies. The population comprised both rural dwellers and urban dwellers, in contrast to previous similar studies involving only urban dwellers. More than 90% of both population groups had ferruginous bodies in their lungs. There was no apparent difference in the incidence or quantity of ferruginous bodies between the group with pulmonary neoplasms and the randomly selected group. These findings raise the possibility of more widespread asbestos dust contamination of environmental air than has been previously thought and indicate that rural as well as urban populations are exposed. The failure to demonstrate more ferruginous bodies in the lungs of patients with pulmonary neoplasms is in accordance with the view that asbestos acts as a cocarcinogen in this regard."} {"id": "PMID:1265495", "title": "Ovarian conservatism.", "content": "Everyone is conscious of the prime role of the ovaries in making a female a \"female.\" However, too little attention has been directed toward the systemic mechanism of estrogens that protects against coronary artery disease and osteoporosis. Exogenous estrogen appears to be almost as effective as the ovaries are in protecting a female from these diseases. The incidence of neoplasia in preserved ovaries after previous pelvic surgery is low. Emphasis has been placed on ovarian conservatism in the young female because a clearer benefit can be demonstrated in them than in postmenopausal females.", "contents": "Ovarian conservatism. Everyone is conscious of the prime role of the ovaries in making a female a \"female.\" However, too little attention has been directed toward the systemic mechanism of estrogens that protects against coronary artery disease and osteoporosis. Exogenous estrogen appears to be almost as effective as the ovaries are in protecting a female from these diseases. The incidence of neoplasia in preserved ovaries after previous pelvic surgery is low. Emphasis has been placed on ovarian conservatism in the young female because a clearer benefit can be demonstrated in them than in postmenopausal females."} {"id": "PMID:1265496", "title": "Malignant thymoma with penetration into the gastrointestinal tract: report of two cases.", "content": "Two cases of thymoma, one epiithelial and one seminoma type are presented. In both instances, the thymoma infiltrated and later perforated the gastrointestinal tract by direct extension. One is the 30th reported case of thymoma with extrathoracic metastasis; this patient had metastasis to the bone marrow and kidney. Neither patient had myasthenia gravis associated with the thymic tumor.", "contents": "Malignant thymoma with penetration into the gastrointestinal tract: report of two cases. Two cases of thymoma, one epiithelial and one seminoma type are presented. In both instances, the thymoma infiltrated and later perforated the gastrointestinal tract by direct extension. One is the 30th reported case of thymoma with extrathoracic metastasis; this patient had metastasis to the bone marrow and kidney. Neither patient had myasthenia gravis associated with the thymic tumor."} {"id": "PMID:1265497", "title": "Smoking among medical students.", "content": "A survey of smoking habits of medical students was done using basic medical science graduate students at the same institution as a comparison group. Smoking status was not significantly related to sex, race, or academic classification. Knowledge of adverse health consequences of smoking was related to time spent in medical school and to whether or not the respondent smoked (ie. probable denial of knowledge of the adverse consequences among smokers). The respondent's smoking status was significantly related to familial and peer group smoking status and to peer group attitude. The most common reason given by quitters was \"the media influence.\" The nonsmoker most frequently never began the habit because of fear of health consequences. Because of the finding that a small percentage of medical students still are not convinced of the dangers of smoking, it was suggested that increased educational emphasis on these dangers be included in the medical curriculum.", "contents": "Smoking among medical students. A survey of smoking habits of medical students was done using basic medical science graduate students at the same institution as a comparison group. Smoking status was not significantly related to sex, race, or academic classification. Knowledge of adverse health consequences of smoking was related to time spent in medical school and to whether or not the respondent smoked (ie. probable denial of knowledge of the adverse consequences among smokers). The respondent's smoking status was significantly related to familial and peer group smoking status and to peer group attitude. The most common reason given by quitters was \"the media influence.\" The nonsmoker most frequently never began the habit because of fear of health consequences. Because of the finding that a small percentage of medical students still are not convinced of the dangers of smoking, it was suggested that increased educational emphasis on these dangers be included in the medical curriculum."} {"id": "PMID:1265498", "title": "The perioperative management of pericardial tamponade.", "content": "A case report of a patient with acute pericardial tamponade is presented. The etiology, pathophysiology, and management of cardiac tamponade is discussed. Preoperative management includes volume expansion, administration of catecholamines, and pericardiocentesis. Intraoperatively, monitoring should include continuous measurement of arterial and central venous pressures. Ketamine has been found to be very useful in these patients.", "contents": "The perioperative management of pericardial tamponade. A case report of a patient with acute pericardial tamponade is presented. The etiology, pathophysiology, and management of cardiac tamponade is discussed. Preoperative management includes volume expansion, administration of catecholamines, and pericardiocentesis. Intraoperatively, monitoring should include continuous measurement of arterial and central venous pressures. Ketamine has been found to be very useful in these patients."} {"id": "PMID:1265499", "title": "Femoropopliteal bypass for salvage and claudication: a comparison of long-term results.", "content": "Seventy-seven femoropopliteal grafts placed for salvage were compared to 51 grafts placed for claudication. Patient profiles of age, preexisting cardiovascular disease, and risk factors were notably similar. Previous vascular procedures were twice as common in the salvage group. The accumulated graft patency in the salvage group of 77% at one month and 58% at two years is compared to 90% and 80% during the same risk intervals in the claudication group. The salvage group sustained 34 complications (44%) and nine deaths (12%), compared to one death (2%) and seven complications (14%) in the claudication group. One half of all grafts placed in diabetic males failed. Nearly half of all early failures were thought to be due to errors of patient selection. Though new technics are making more extremities potentially salvageable, this study suggests that improved patient selection will be necessary to lower high complication rates.", "contents": "Femoropopliteal bypass for salvage and claudication: a comparison of long-term results. Seventy-seven femoropopliteal grafts placed for salvage were compared to 51 grafts placed for claudication. Patient profiles of age, preexisting cardiovascular disease, and risk factors were notably similar. Previous vascular procedures were twice as common in the salvage group. The accumulated graft patency in the salvage group of 77% at one month and 58% at two years is compared to 90% and 80% during the same risk intervals in the claudication group. The salvage group sustained 34 complications (44%) and nine deaths (12%), compared to one death (2%) and seven complications (14%) in the claudication group. One half of all grafts placed in diabetic males failed. Nearly half of all early failures were thought to be due to errors of patient selection. Though new technics are making more extremities potentially salvageable, this study suggests that improved patient selection will be necessary to lower high complication rates."} {"id": "PMID:1265500", "title": "Delayed hypersensitivity skin testing for assessing anergy in the mid-south.", "content": "Although skin testing with ubiquitous antigens is widely employed to assess delayed hypersensitivity, little is known about the effect of geographic location on the frequency of skin test reactions to given antigens. To assess skin test reactivity in the mid-South, 82 hospitalized patients and 68 normal controls had skin tests with six antigens: histoplasmin, mumps, tuberculin purified protein derivative (PPD), Candida, Trichophyton, and streptokinase-streptodornase. Ninety-five percent of normal and 79% of hospitalized subjects without immunologically related disease reacted to at least one of the antigens. A high rate of anergy was found in a clinical setting of debilitation and malnutrition. If subjects in poor condition also were excluded, 93% of hospitalized patients reacted to at least one antigen. Rates of reactivity increased with higher concentrations of antigen. To assess anergy in the mid-South, it is recommended that patients be skin tested initially with histoplasmin, mumps, and PPD antigens. If the patient does not react to any of these, streptokinase-streptodornase and Candida albicans (Dermatophytin \"O\") should be applied.", "contents": "Delayed hypersensitivity skin testing for assessing anergy in the mid-south. Although skin testing with ubiquitous antigens is widely employed to assess delayed hypersensitivity, little is known about the effect of geographic location on the frequency of skin test reactions to given antigens. To assess skin test reactivity in the mid-South, 82 hospitalized patients and 68 normal controls had skin tests with six antigens: histoplasmin, mumps, tuberculin purified protein derivative (PPD), Candida, Trichophyton, and streptokinase-streptodornase. Ninety-five percent of normal and 79% of hospitalized subjects without immunologically related disease reacted to at least one of the antigens. A high rate of anergy was found in a clinical setting of debilitation and malnutrition. If subjects in poor condition also were excluded, 93% of hospitalized patients reacted to at least one antigen. Rates of reactivity increased with higher concentrations of antigen. To assess anergy in the mid-South, it is recommended that patients be skin tested initially with histoplasmin, mumps, and PPD antigens. If the patient does not react to any of these, streptokinase-streptodornase and Candida albicans (Dermatophytin \"O\") should be applied."} {"id": "PMID:1265501", "title": "Eosinophilic gastroenteritis.", "content": "Four patients with eosinophilic gastroenteritis are presented to illustrate the protean manifestations of this disorder. While the cause is unknown, the complications many, and the differential diagnosis often challenging, the treatment is simple and consists of low-dose, alternate-day administration of corticosteroids. Diagnosis depends on gastrointestinal biopsy, which usually can be obtained without surgery.", "contents": "Eosinophilic gastroenteritis. Four patients with eosinophilic gastroenteritis are presented to illustrate the protean manifestations of this disorder. While the cause is unknown, the complications many, and the differential diagnosis often challenging, the treatment is simple and consists of low-dose, alternate-day administration of corticosteroids. Diagnosis depends on gastrointestinal biopsy, which usually can be obtained without surgery."} {"id": "PMID:1265502", "title": "Gastric emptying of hypertonic glucose in diabetes mellitus and duodenal ulcer.", "content": "Gastric emptying of hypertonic glucose liquid meals was studied in diabetes, duodenal ulcer, and hospitalized controls by means of the 10% glucose 30-minute test meal, with phenol red as nonabsorbable marker. Acid secreted into the meal was measured. Results revealed no significant difference in gastric emptying between controls and patients with duodenal ulcer and diabetes mellitus. Among diabetics, some individuals empty this meal more rapidly than normal. The results show that alterations of gastric emptying cannot account for the late peaks observed on oral glucose tolerance tests in diabetics, nor for any tendency toward reactive hypoglycemia in duodenal ulcer. They suggest that autovagotomy may occur in some diabetics.", "contents": "Gastric emptying of hypertonic glucose in diabetes mellitus and duodenal ulcer. Gastric emptying of hypertonic glucose liquid meals was studied in diabetes, duodenal ulcer, and hospitalized controls by means of the 10% glucose 30-minute test meal, with phenol red as nonabsorbable marker. Acid secreted into the meal was measured. Results revealed no significant difference in gastric emptying between controls and patients with duodenal ulcer and diabetes mellitus. Among diabetics, some individuals empty this meal more rapidly than normal. The results show that alterations of gastric emptying cannot account for the late peaks observed on oral glucose tolerance tests in diabetics, nor for any tendency toward reactive hypoglycemia in duodenal ulcer. They suggest that autovagotomy may occur in some diabetics."} {"id": "PMID:1265503", "title": "Polydactyly: report of a large kindred.", "content": "The occurrence of polydactyly in a 33-year-old woman with a patent ductus arteriosus stimulated a study of her family. Four generations of her kindred were examined. No other case of congenital heart disease was discovered, but a large number of individuals with polydactyly were found. Inheritance of this trait is autosomal dominant.", "contents": "Polydactyly: report of a large kindred. The occurrence of polydactyly in a 33-year-old woman with a patent ductus arteriosus stimulated a study of her family. Four generations of her kindred were examined. No other case of congenital heart disease was discovered, but a large number of individuals with polydactyly were found. Inheritance of this trait is autosomal dominant."} {"id": "PMID:1265504", "title": "Metastatic carcinoma in histologic sections of aspirated bone marrow: a comparative autopsy study.", "content": "The incidence of metastatic carcinoma in bone marrow was studied by two different approaches in 220 consecutive autopsies of patients with carcinoma: histologic sections of aspirates from the iliac spine, as usually done in living patients; and gross and microscopic examination of the thoracolumbar spine. Ten percent of the autopsies showed bone marrow metastases by the aspiration technic as contrasted with 34.5% by the autopsy technic. Three cases had positive bone marrow aspirates in the absence of metastases demonstrable by routine autopsy. The combination of autopsy and aspiration technics yielded an incidence of metastatic marrow involvement of 35.9%. Of patients with marrow metastases at autopsy, 25% also had positive aspirates. This study establishes a norm for the comparison of the efficiency of discovery of metastatic carcinoma by different modalities of clinical bone marrow sampling.", "contents": "Metastatic carcinoma in histologic sections of aspirated bone marrow: a comparative autopsy study. The incidence of metastatic carcinoma in bone marrow was studied by two different approaches in 220 consecutive autopsies of patients with carcinoma: histologic sections of aspirates from the iliac spine, as usually done in living patients; and gross and microscopic examination of the thoracolumbar spine. Ten percent of the autopsies showed bone marrow metastases by the aspiration technic as contrasted with 34.5% by the autopsy technic. Three cases had positive bone marrow aspirates in the absence of metastases demonstrable by routine autopsy. The combination of autopsy and aspiration technics yielded an incidence of metastatic marrow involvement of 35.9%. Of patients with marrow metastases at autopsy, 25% also had positive aspirates. This study establishes a norm for the comparison of the efficiency of discovery of metastatic carcinoma by different modalities of clinical bone marrow sampling."} {"id": "PMID:1265505", "title": "Pauciarticular juvenile arthritis.", "content": "Pauciarticular juvenile arthritis begins insidiously, involves no more than five joints, causes few systemic symptoms, and has a relatively mild course. The disease may recur at the same site or in previously uninvolved joints. It generally runs its course in four years. The authors believe that synovectomy is contraindicated in children suspected of having this mild form of arthritis unless joint destruction is evident or symptoms progress for more than three years.", "contents": "Pauciarticular juvenile arthritis. Pauciarticular juvenile arthritis begins insidiously, involves no more than five joints, causes few systemic symptoms, and has a relatively mild course. The disease may recur at the same site or in previously uninvolved joints. It generally runs its course in four years. The authors believe that synovectomy is contraindicated in children suspected of having this mild form of arthritis unless joint destruction is evident or symptoms progress for more than three years."} {"id": "PMID:1265506", "title": "Recent survey of infectious meningitis in adults: review of laboratory findings in bacterial, tuberculous, and aseptic meningitis.", "content": "Infectious meningitis in adults was reviewed to establish the frequency of meningitis due to each causative agent and to reexamine the laboratory parameters that help to distinguish aseptic, bacterial, and mycobacterial meningitis. Aseptic meningitis occurred 2.2 times more often than bacterial and mycobacterial meningitis combined. The most common nonviral causative agent was the pneumococcus (23 cases) followed by the tubercle bacillus (11 cases) and the meningococcus (5 cases). Cerebrospinal fluid (CSF) Gram stain was the most useful study to rule in a bacterial cause: 89% of cases of bacterial meningitis had a positive initial Gram stain. Hyponatremia occurred in 73% of cases of tuberculous meningitis; hyponatremia combined with a negative Gram stain was highly suggestive of a tuberculous cause. One third of all patients with tuberculous and aseptic meningitis had a predominance of neutrophils in the CSF. No patient with aseptic meningitis had a CSF while count higher than 2,800 cells/cu mm or a CSF protein value higher than 250 mg/100 ml. Other reviews confirm this if cases due to lymphocytic choriomeningitis (LCM) are excluded. One patient with tuberculous meningitis in this series, and none of those cases reviewed, had a CSF white count higher than 1,200 cells/cu mm. Only 3.7% of the patients with aseptic meningitis had hypoglycorrhachia. Series reporting exclusively disease due to mumps and LCM have a higher frequency of hypoglycorrhachia.", "contents": "Recent survey of infectious meningitis in adults: review of laboratory findings in bacterial, tuberculous, and aseptic meningitis. Infectious meningitis in adults was reviewed to establish the frequency of meningitis due to each causative agent and to reexamine the laboratory parameters that help to distinguish aseptic, bacterial, and mycobacterial meningitis. Aseptic meningitis occurred 2.2 times more often than bacterial and mycobacterial meningitis combined. The most common nonviral causative agent was the pneumococcus (23 cases) followed by the tubercle bacillus (11 cases) and the meningococcus (5 cases). Cerebrospinal fluid (CSF) Gram stain was the most useful study to rule in a bacterial cause: 89% of cases of bacterial meningitis had a positive initial Gram stain. Hyponatremia occurred in 73% of cases of tuberculous meningitis; hyponatremia combined with a negative Gram stain was highly suggestive of a tuberculous cause. One third of all patients with tuberculous and aseptic meningitis had a predominance of neutrophils in the CSF. No patient with aseptic meningitis had a CSF while count higher than 2,800 cells/cu mm or a CSF protein value higher than 250 mg/100 ml. Other reviews confirm this if cases due to lymphocytic choriomeningitis (LCM) are excluded. One patient with tuberculous meningitis in this series, and none of those cases reviewed, had a CSF white count higher than 1,200 cells/cu mm. Only 3.7% of the patients with aseptic meningitis had hypoglycorrhachia. Series reporting exclusively disease due to mumps and LCM have a higher frequency of hypoglycorrhachia."} {"id": "PMID:1265507", "title": "Mikulicz's disease and Mikulicz's syndrome.", "content": "The pathogenesis, clinical manifestations, and historical development of Mikulicz's disease and Mikulicz's syndrome are given. It is recommended that the term \"Mikulicz's syndrome\" be dropped to avoid confusion with the rare and well defined entity \"Mikulicz's disease.\"", "contents": "Mikulicz's disease and Mikulicz's syndrome. The pathogenesis, clinical manifestations, and historical development of Mikulicz's disease and Mikulicz's syndrome are given. It is recommended that the term \"Mikulicz's syndrome\" be dropped to avoid confusion with the rare and well defined entity \"Mikulicz's disease.\""} {"id": "PMID:1265508", "title": "Neurilemoma presenting as a lump in the breast.", "content": "A neurilemoma arising in breast tissue is reported. Neurilemomas are usually well circumscribed and non-invasive, but may be confused with cystosarcoma phylloides, particularly in frozen section. Pertinent pathologic findings are described, and the literature is reviewed. Only one case of neurilemoma in the breast has previously been reported.", "contents": "Neurilemoma presenting as a lump in the breast. A neurilemoma arising in breast tissue is reported. Neurilemomas are usually well circumscribed and non-invasive, but may be confused with cystosarcoma phylloides, particularly in frozen section. Pertinent pathologic findings are described, and the literature is reviewed. Only one case of neurilemoma in the breast has previously been reported."} {"id": "PMID:1265509", "title": "Photosensitivity papules--a cutaneous sign of systemic disease: erythropoietic protoporphyria.", "content": "Erythropoietic protoporphyria is an unusual autosomal dominant syndrome characterized by increased deposits of protoporphyrin in erythrocytes, liver, feces, and skin. Symptomatic chronic cutaneous papules in sun-exposed areas, cholelithiasis, cirrhosis, hepatic failure, and anemia are manifestations of this systemic disorder. Treatment of cutaneous symptoms is with oral beta-carotene, but there is no effective control for internal manifestations.", "contents": "Photosensitivity papules--a cutaneous sign of systemic disease: erythropoietic protoporphyria. Erythropoietic protoporphyria is an unusual autosomal dominant syndrome characterized by increased deposits of protoporphyrin in erythrocytes, liver, feces, and skin. Symptomatic chronic cutaneous papules in sun-exposed areas, cholelithiasis, cirrhosis, hepatic failure, and anemia are manifestations of this systemic disorder. Treatment of cutaneous symptoms is with oral beta-carotene, but there is no effective control for internal manifestations."} {"id": "PMID:1265510", "title": "Adverse effects of transfusions.", "content": "The risks of morbidity and mortality associated with transfusion are so great that no transfusion should be given until it is decided that it is absolutely necessary and then only with the utmost care. The unfavorable effects of transfusion reviewed are: hemolytic reaction; bacterial contamination; febrile reaction due to leukoagglutinins; urticaria; anaphylaxis; problems associated with the transfusion of excess potassium, ammonia, and acid; transmission of hepatitis, cytomegalic inclusion disease, toxoplasmosis, and malaria; pulmonary insufficiency; air embolism; and circulatory overload.", "contents": "Adverse effects of transfusions. The risks of morbidity and mortality associated with transfusion are so great that no transfusion should be given until it is decided that it is absolutely necessary and then only with the utmost care. The unfavorable effects of transfusion reviewed are: hemolytic reaction; bacterial contamination; febrile reaction due to leukoagglutinins; urticaria; anaphylaxis; problems associated with the transfusion of excess potassium, ammonia, and acid; transmission of hepatitis, cytomegalic inclusion disease, toxoplasmosis, and malaria; pulmonary insufficiency; air embolism; and circulatory overload."} {"id": "PMID:1265511", "title": "Macrocheilia due to lymphangiectasia.", "content": "A case of symmetrical, diffuse macrocheilia due to lymphangiectasia is presented. No primary cause for this case or for many other pathologic forms of macrocheilia has been established. Tranverse mucosal wedge resection of the lip with mucosal advancement, however, is a satisfactory method of treatment.", "contents": "Macrocheilia due to lymphangiectasia. A case of symmetrical, diffuse macrocheilia due to lymphangiectasia is presented. No primary cause for this case or for many other pathologic forms of macrocheilia has been established. Tranverse mucosal wedge resection of the lip with mucosal advancement, however, is a satisfactory method of treatment."} {"id": "PMID:1265512", "title": "Recurring spontaneous pneumothorax associated with menses.", "content": "A case of catamenial pneumothorax in a 34-year-old woman is presented. Typically recurrent, right-sided pneumothorax associated with menses occurs in a 30- to 40-year-old woman with endometriosis. The right-sided occurrence is attributed to the frequency of congenital perforations of the right hemidiaphragm. Aberrant endometrial tissue is thought to gain access to the right hemithorax and cause pneumothorax with the menstrual slough. Therapy consists of ovulation-suppressing drugs or thoracotomy with pleural ablation for recurrent pneumothoraces. The physician should be aware of the syndrome to make a proper diagnosis.", "contents": "Recurring spontaneous pneumothorax associated with menses. A case of catamenial pneumothorax in a 34-year-old woman is presented. Typically recurrent, right-sided pneumothorax associated with menses occurs in a 30- to 40-year-old woman with endometriosis. The right-sided occurrence is attributed to the frequency of congenital perforations of the right hemidiaphragm. Aberrant endometrial tissue is thought to gain access to the right hemithorax and cause pneumothorax with the menstrual slough. Therapy consists of ovulation-suppressing drugs or thoracotomy with pleural ablation for recurrent pneumothoraces. The physician should be aware of the syndrome to make a proper diagnosis."} {"id": "PMID:1265513", "title": "Intramural hematoma of the duodenum.", "content": "A case concerning a patient with an intramural hematoma involving the first and second portions of the duodenum was presented with a brief review of etiology, pathogenesis, clinical features, and management. An intramural hematoma usually occurs after blunt trauma, manifesting clinically as a high small bowel obstruction with a palpable mass. Roentgenograms usually confirm the diagnosis and treatment in simple evacuation of the hematoma.", "contents": "Intramural hematoma of the duodenum. A case concerning a patient with an intramural hematoma involving the first and second portions of the duodenum was presented with a brief review of etiology, pathogenesis, clinical features, and management. An intramural hematoma usually occurs after blunt trauma, manifesting clinically as a high small bowel obstruction with a palpable mass. Roentgenograms usually confirm the diagnosis and treatment in simple evacuation of the hematoma."} {"id": "PMID:1265514", "title": "Leiomyoma arising adjacent to a maxillary tooth socket: an intraosseous leiomyoma presenting as an odontogenic lesion.", "content": "An intraosseous leiomyoma involving a maxillary tooth socket is described and previous reports of oral leiomyomas are reviewed. This is the first case report of an intraosseous leiomyoma. Although theoretically it could be of odontogenic origin, the tumor probably arose from vascular smooth muscle or bone.", "contents": "Leiomyoma arising adjacent to a maxillary tooth socket: an intraosseous leiomyoma presenting as an odontogenic lesion. An intraosseous leiomyoma involving a maxillary tooth socket is described and previous reports of oral leiomyomas are reviewed. This is the first case report of an intraosseous leiomyoma. Although theoretically it could be of odontogenic origin, the tumor probably arose from vascular smooth muscle or bone."} {"id": "PMID:1265515", "title": "Colitis cystica profunda.", "content": "The 50th reported case of colitis cystica profunda, with coexisting carcinoma in situ, was found. The diagnosis was made after a second excisional biopsy. The lesion was excised locally, and no recurrence has been observed one year after operation.", "contents": "Colitis cystica profunda. The 50th reported case of colitis cystica profunda, with coexisting carcinoma in situ, was found. The diagnosis was made after a second excisional biopsy. The lesion was excised locally, and no recurrence has been observed one year after operation."} {"id": "PMID:1265516", "title": "Weber-Christian disease after weight loss.", "content": "Weber-Christian disease has no known cause and is characterized by a febrile, recurrent, nonsuppurative panniculitis occurring preferentially in young, obese women. The present case is of interest in that it occurred in a young, obese woman after she lost 18.2 kg (40 lb) in eight weeks. It is only speculative as to whether the sudden weight loss precipitated the Weber-Christian disease. However, since Weber-Christian disease is an obscure disease with metabolic and autoimmune overtones, such a hypothesis is not unrealistic in a predisposed individual.", "contents": "Weber-Christian disease after weight loss. Weber-Christian disease has no known cause and is characterized by a febrile, recurrent, nonsuppurative panniculitis occurring preferentially in young, obese women. The present case is of interest in that it occurred in a young, obese woman after she lost 18.2 kg (40 lb) in eight weeks. It is only speculative as to whether the sudden weight loss precipitated the Weber-Christian disease. However, since Weber-Christian disease is an obscure disease with metabolic and autoimmune overtones, such a hypothesis is not unrealistic in a predisposed individual."} {"id": "PMID:1265517", "title": "Neoplasia of the colon: a late complication of ureterosigmoidostomy.", "content": "A case of carcinoma of the sigmoid colon arising 26 years after ureterosigmoidostomy for a benign condition is presented. This is the 31st reported instance of neoplasia complicating ureterosigmoid diversion. Possible etiologic mechanisms include surgical trauma, constant irritation of the transplanted ureter, alteration of local tissue dynamics, and urine carcinogenesis.", "contents": "Neoplasia of the colon: a late complication of ureterosigmoidostomy. A case of carcinoma of the sigmoid colon arising 26 years after ureterosigmoidostomy for a benign condition is presented. This is the 31st reported instance of neoplasia complicating ureterosigmoid diversion. Possible etiologic mechanisms include surgical trauma, constant irritation of the transplanted ureter, alteration of local tissue dynamics, and urine carcinogenesis."} {"id": "PMID:1265518", "title": "Ichthyosiform scaling in association with lymphoma.", "content": "A patient is described who developed ichthyosiform scaling in association with localized Hodgkin's disease. The scaling subsequently cleared following initial successful radiotherapy of the tumor. The scaling has not returned with two recurrences of the lymphoma during a five-year period.", "contents": "Ichthyosiform scaling in association with lymphoma. A patient is described who developed ichthyosiform scaling in association with localized Hodgkin's disease. The scaling subsequently cleared following initial successful radiotherapy of the tumor. The scaling has not returned with two recurrences of the lymphoma during a five-year period."} {"id": "PMID:1265519", "title": "Death due to fluorocarbon inhalation.", "content": "The abuse of inhalation of aerosol preparations containing fluorocarbons as the propellant is a potentially lethal act. I report a death believed due to inhalation of an aerosol propellant.", "contents": "Death due to fluorocarbon inhalation. The abuse of inhalation of aerosol preparations containing fluorocarbons as the propellant is a potentially lethal act. I report a death believed due to inhalation of an aerosol propellant."} {"id": "PMID:1265520", "title": "Systemic lupus erythematosus: unusual presentation with gastric polyps and vasculitis.", "content": "A case of SLE with the unique association of gastric polyps and vasculitis is reported. Gastrointestinal symptoms, surgical indications, and complications of SLE with gastrointestinal involvement are reviewed. The unusual patterns of ileus or lupus peritonitis secondary to mesenteric vasculitis must be differentiated from a true surgical emergency. Corticosteroids may be expected to produce rapid clinical improvement in the two former instances. Surgical exploration is reserved for those cases with clinical or radiologic evidence of uncontrollable hemorrhage, bowel perforation, or mesenteric infarction.", "contents": "Systemic lupus erythematosus: unusual presentation with gastric polyps and vasculitis. A case of SLE with the unique association of gastric polyps and vasculitis is reported. Gastrointestinal symptoms, surgical indications, and complications of SLE with gastrointestinal involvement are reviewed. The unusual patterns of ileus or lupus peritonitis secondary to mesenteric vasculitis must be differentiated from a true surgical emergency. Corticosteroids may be expected to produce rapid clinical improvement in the two former instances. Surgical exploration is reserved for those cases with clinical or radiologic evidence of uncontrollable hemorrhage, bowel perforation, or mesenteric infarction."} {"id": "PMID:1265521", "title": "Metastatic carcinoma in meningioma.", "content": "A case of adenocarcinoma of the lung metastatic to two of three parasagittal meningiomas is presented. This is the tenth reported case of carcinoma metastatic to a meningioma.", "contents": "Metastatic carcinoma in meningioma. A case of adenocarcinoma of the lung metastatic to two of three parasagittal meningiomas is presented. This is the tenth reported case of carcinoma metastatic to a meningioma."} {"id": "PMID:1265522", "title": "Choledochoduodenostomy: an answer to some biliary surgical problems.", "content": "In the presence of a primary stasis stone, ampullary obstruction, and a massively dilated common bile duct, choledochoduodenostomy should be considered. Because of infrequent need, surgeons may hesitate to utilize this valuable procedure; however, it may be the most expeditious and safest method of treating complex biliary problems. Neither ascending cholangitis nor stasis in the remaining distally obstructed duct appear to be a problem if an adequate stoma is established. A case report was included to emphasize the problem and the solution.", "contents": "Choledochoduodenostomy: an answer to some biliary surgical problems. In the presence of a primary stasis stone, ampullary obstruction, and a massively dilated common bile duct, choledochoduodenostomy should be considered. Because of infrequent need, surgeons may hesitate to utilize this valuable procedure; however, it may be the most expeditious and safest method of treating complex biliary problems. Neither ascending cholangitis nor stasis in the remaining distally obstructed duct appear to be a problem if an adequate stoma is established. A case report was included to emphasize the problem and the solution."} {"id": "PMID:1265523", "title": "Chronic arachnoiditis after a pantopaque study of the posterior fossa.", "content": "Reported is a case in which chronic arachnoiditis resulted as a complication of using Pantopaque in studying the posterior fossa. The possibility that prophylactic intrathecal injections of methylprednisolone acetate while performing Pantopaque myelography help avoid serious complications is discussed.", "contents": "Chronic arachnoiditis after a pantopaque study of the posterior fossa. Reported is a case in which chronic arachnoiditis resulted as a complication of using Pantopaque in studying the posterior fossa. The possibility that prophylactic intrathecal injections of methylprednisolone acetate while performing Pantopaque myelography help avoid serious complications is discussed."} {"id": "PMID:1265539", "title": "The mortality and morbidity of laryngectomy.", "content": "Experiences with 147 laryngectomies, 49 with en bloc neck dissection, are presented. One patient died, and 36 suffered postoperative complications serious enough to delay rehabilitation and to prolong hospitalisation.", "contents": "The mortality and morbidity of laryngectomy. Experiences with 147 laryngectomies, 49 with en bloc neck dissection, are presented. One patient died, and 36 suffered postoperative complications serious enough to delay rehabilitation and to prolong hospitalisation."} {"id": "PMID:1265540", "title": "A forward view of health services in South Africa.", "content": "This article is an exposition of health services, past, present and future, in the Republic of South Africa, with particular reference to the Black homelands and their development in the fields of personal health services, nutritional services and laboratory services. It also deals with manpower resources and medical aid.", "contents": "A forward view of health services in South Africa. This article is an exposition of health services, past, present and future, in the Republic of South Africa, with particular reference to the Black homelands and their development in the fields of personal health services, nutritional services and laboratory services. It also deals with manpower resources and medical aid."} {"id": "PMID:1265541", "title": "Acute leukaemia and allogeneic granulocyte support.", "content": "Infusion of functional allogeneic granulocytes is rational therapy in pyrexial patients with severe neutropenia when combined with appropriate antibiotic administration. On the basis of our first year's experience we endorse this approach, but emphasise the need for further critical evaluation of these cells, and present an approach to placing this procedure on a more scientific basis.", "contents": "Acute leukaemia and allogeneic granulocyte support. Infusion of functional allogeneic granulocytes is rational therapy in pyrexial patients with severe neutropenia when combined with appropriate antibiotic administration. On the basis of our first year's experience we endorse this approach, but emphasise the need for further critical evaluation of these cells, and present an approach to placing this procedure on a more scientific basis."} {"id": "PMID:1265542", "title": "Treponemal depigmentation, with special reference to yaws.", "content": "Depigmentation of the skin at characteristic sites occurs in all the treponematoses, but it is seen most commonly in older persons who have had yaws in infancy or childhood, especially when treatment has been inadequate to prevent this tertiary manifestation. A total of 689 cases are recorded from the former Belgian Congo.", "contents": "Treponemal depigmentation, with special reference to yaws. Depigmentation of the skin at characteristic sites occurs in all the treponematoses, but it is seen most commonly in older persons who have had yaws in infancy or childhood, especially when treatment has been inadequate to prevent this tertiary manifestation. A total of 689 cases are recorded from the former Belgian Congo."} {"id": "PMID:1265543", "title": "The role of Mycoplasma in human infertility.", "content": "Seminal fluid from males complaining of infertility was examined for the presence of T-mycoplasmas and Mycoplasma hominis. No significant difference, with regard to the presence of mycoplasmas, was found between the seminal fluid which had normal cytology and seminal fluid of which the cytology was deemed pathological. Colonisation was shown to be an evanescent phenomenon, and female consorts often had different mycoplasma flora to the males. No positive role of mycoplasmas in the pathogenesis of infertility could be shown.", "contents": "The role of Mycoplasma in human infertility. Seminal fluid from males complaining of infertility was examined for the presence of T-mycoplasmas and Mycoplasma hominis. No significant difference, with regard to the presence of mycoplasmas, was found between the seminal fluid which had normal cytology and seminal fluid of which the cytology was deemed pathological. Colonisation was shown to be an evanescent phenomenon, and female consorts often had different mycoplasma flora to the males. No positive role of mycoplasmas in the pathogenesis of infertility could be shown."} {"id": "PMID:1265544", "title": "Multiple therapist groups in a day-patient setting and some aspects of group geography.", "content": "The pros and cons of multiple therapist groups are considered from both the patient's and the therapist's points of view. Some aspects of group geography and how this may affect group activity, are examined. The significance among selected patients of preferential seating and how activity in the group varied with this, is discussed.", "contents": "Multiple therapist groups in a day-patient setting and some aspects of group geography. The pros and cons of multiple therapist groups are considered from both the patient's and the therapist's points of view. Some aspects of group geography and how this may affect group activity, are examined. The significance among selected patients of preferential seating and how activity in the group varied with this, is discussed."} {"id": "PMID:1265545", "title": "Induction of labour in Black patients.", "content": "The results of a prospective study of induction of labour in 175 Black patients are presented. They show that induction of labour in Blacks, even when performed with optimal care, is more hazardous than in other population groups, owing to an increased proportion of patients of high parity and an increased prevalence of cephalopelvic disproportion. The factors affecting the outcome of induction, the safety of induction and the criteria for a safer induction are discussed.", "contents": "Induction of labour in Black patients. The results of a prospective study of induction of labour in 175 Black patients are presented. They show that induction of labour in Blacks, even when performed with optimal care, is more hazardous than in other population groups, owing to an increased proportion of patients of high parity and an increased prevalence of cephalopelvic disproportion. The factors affecting the outcome of induction, the safety of induction and the criteria for a safer induction are discussed."} {"id": "PMID:1265546", "title": "Abdominal paracentesis in the diagnosis of ruptured ectopic pregnancy.", "content": "A prospective study of the use of abdominal paracentesis in the diagnosis of suspected ectopic pregnancy was carried out. Paracentesis was performed in 189 patients, of whom 132 were subsequently shown to have ectopic pregnancies. Paracentesis confirmed the diagnosis in 90,9% of cases, but when this was corrected to exclude cases where no intraperitoneal haemorrhage was present, the success rate rose to 96,3%. We believe that this simple, harmless, bedside procedure has value in aiding and confirming the diagnosis of ruptured ectopic pregnancy.", "contents": "Abdominal paracentesis in the diagnosis of ruptured ectopic pregnancy. A prospective study of the use of abdominal paracentesis in the diagnosis of suspected ectopic pregnancy was carried out. Paracentesis was performed in 189 patients, of whom 132 were subsequently shown to have ectopic pregnancies. Paracentesis confirmed the diagnosis in 90,9% of cases, but when this was corrected to exclude cases where no intraperitoneal haemorrhage was present, the success rate rose to 96,3%. We believe that this simple, harmless, bedside procedure has value in aiding and confirming the diagnosis of ruptured ectopic pregnancy."} {"id": "PMID:1265547", "title": "Rupture of the uterus: the preventable factors.", "content": "A review of 50 cases of ruptured uterus revealed that important measures to prevent this serious complication are: good antenatal care; careful attention to patients who have had a previous Caesarean section; the correct management of cephalopelvic disproportion in the multigravida; the recognition of the serious hazards of internal version in the management of transverse lie; and careful attention to detail in the use of oxytocin in the multigravida. The factors that were regarded as critical in maintaining a low maternal mortality rate in rupture of the uterus are also reviewed.", "contents": "Rupture of the uterus: the preventable factors. A review of 50 cases of ruptured uterus revealed that important measures to prevent this serious complication are: good antenatal care; careful attention to patients who have had a previous Caesarean section; the correct management of cephalopelvic disproportion in the multigravida; the recognition of the serious hazards of internal version in the management of transverse lie; and careful attention to detail in the use of oxytocin in the multigravida. The factors that were regarded as critical in maintaining a low maternal mortality rate in rupture of the uterus are also reviewed."} {"id": "PMID:1265548", "title": "Intra-amniotic use of urea and prostaglandin F2 alpha to induce labour in pregnancies complicated by death of the fetus.", "content": "A simple, safe and efficient method of inducing labor in patients in whom pregnancy is complicated by intrauterine death of the fetus is described. The technique involves a single intra-amniotic infusion of 30 mg of prostaglandin F2alpha with 60 g of urea. Fourteen pregnancies complicated by intra-uterine fetal death (ranging in duration from 1 to 7 1/2 weeks) were successfully terminated by this method. Side-effects and complications were minimal. It is submitted that this method provides the obstetrician with a valuable addition to his therapeutic armamentarium. If correctly employed, it provides rapid delivery with minimal risk of discomfort to the patient.", "contents": "Intra-amniotic use of urea and prostaglandin F2 alpha to induce labour in pregnancies complicated by death of the fetus. A simple, safe and efficient method of inducing labor in patients in whom pregnancy is complicated by intrauterine death of the fetus is described. The technique involves a single intra-amniotic infusion of 30 mg of prostaglandin F2alpha with 60 g of urea. Fourteen pregnancies complicated by intra-uterine fetal death (ranging in duration from 1 to 7 1/2 weeks) were successfully terminated by this method. Side-effects and complications were minimal. It is submitted that this method provides the obstetrician with a valuable addition to his therapeutic armamentarium. If correctly employed, it provides rapid delivery with minimal risk of discomfort to the patient."} {"id": "PMID:1265549", "title": "Postabortal and postpartum tetanus. A review of 19 cases.", "content": "The occurrence of postabortal and postpartum tetanus over a 7 1/2-year period at Groote Schuur Hospital, Cape Town, is reviewed. Of all the women between the ages of 15 years and 50 years who were admitted with tetanus, 34,7% were admitted after abortions. The mortality rate was 15,8%, which appears to be the lowest thus far reported. Possible methods of preventing postabortal tetanus are discussed.", "contents": "Postabortal and postpartum tetanus. A review of 19 cases. The occurrence of postabortal and postpartum tetanus over a 7 1/2-year period at Groote Schuur Hospital, Cape Town, is reviewed. Of all the women between the ages of 15 years and 50 years who were admitted with tetanus, 34,7% were admitted after abortions. The mortality rate was 15,8%, which appears to be the lowest thus far reported. Possible methods of preventing postabortal tetanus are discussed."} {"id": "PMID:1265550", "title": "Comparison of oral prostaglandin E2 and intravenous oxytocin for induction of labour.", "content": "A carefully controlled, prospective study was undertaken in 100 patients to compare orally administered prostaglandin E2 capsules with intravenous oxytocin in the induction of labour at term. Orally administered prostaglandin E2 induced labour in slightly more patients than did intravenous oxytocin (48 out of 50 v. 45 out of 50) and a larger trail is in progress to evaluate this observation further. Mild gastro-intestinal symptoms occurred in 28% of the patients when oral prostaglandin was given. However, the oral route is more convenient and more comfortable for the patient and the administration requires less adjustment by the nursing staff.", "contents": "Comparison of oral prostaglandin E2 and intravenous oxytocin for induction of labour. A carefully controlled, prospective study was undertaken in 100 patients to compare orally administered prostaglandin E2 capsules with intravenous oxytocin in the induction of labour at term. Orally administered prostaglandin E2 induced labour in slightly more patients than did intravenous oxytocin (48 out of 50 v. 45 out of 50) and a larger trail is in progress to evaluate this observation further. Mild gastro-intestinal symptoms occurred in 28% of the patients when oral prostaglandin was given. However, the oral route is more convenient and more comfortable for the patient and the administration requires less adjustment by the nursing staff."} {"id": "PMID:1265551", "title": "Treatment of anovulation with human menopausal gonadotrophin.", "content": "A method is presented of gonadotrophin administration and serum 17beta-oestradiol monitoring for the treatment of anovulation. Four of the 6 patients treated have conceived without any undesirable effects due to hyperstimulation. The advantages of this method of treatment and monitoring are discussed.", "contents": "Treatment of anovulation with human menopausal gonadotrophin. A method is presented of gonadotrophin administration and serum 17beta-oestradiol monitoring for the treatment of anovulation. Four of the 6 patients treated have conceived without any undesirable effects due to hyperstimulation. The advantages of this method of treatment and monitoring are discussed."} {"id": "PMID:1265553", "title": "Scanning electron microscopy of normal uterine cervix, carcinoma in situ and squamous cell carcinoma. Preliminary findings.", "content": "Colposcopically directed punch biopsy specimens of the uterine cervix were taken from women in whom Papanicolaou smears indicated cytological abnormalities. Half of each specimen was processed for scanning electron microscopy and half for light microscopy. The surface morphology of normal cervical, metaplastic and frankly carcinomatous epithelia and epithelia of carcinoma in situ, as seen under the scanning electron microscope, was compared with the appearance revealed by Papanicolaou smears, and haematoxylin- and eosin-stained sections.", "contents": "Scanning electron microscopy of normal uterine cervix, carcinoma in situ and squamous cell carcinoma. Preliminary findings. Colposcopically directed punch biopsy specimens of the uterine cervix were taken from women in whom Papanicolaou smears indicated cytological abnormalities. Half of each specimen was processed for scanning electron microscopy and half for light microscopy. The surface morphology of normal cervical, metaplastic and frankly carcinomatous epithelia and epithelia of carcinoma in situ, as seen under the scanning electron microscope, was compared with the appearance revealed by Papanicolaou smears, and haematoxylin- and eosin-stained sections."} {"id": "PMID:1265554", "title": "Misconceptions and miscarriages in multiple choice questions.", "content": "A modification of the standard format of multiple choice question (MCQ) examinations, recently introduced in certain medical schools in this country, is decribed. The scheme allows for the variation of marks allocated to different in the paper, depending upon the relevance, importance and degree of difficulty of each question. However, the manner in which this new system is being implemented in some cases transgresses some fundamental principles of MCQ examinations. The consequence of this is that the average mark for the class is unintentionally low, with the good students separated from the main body of the class by a disproportionate number of marks. In addition, the examination lends itself to abuse by the enterprising student who is familar with the system of mark allocation.", "contents": "Misconceptions and miscarriages in multiple choice questions. A modification of the standard format of multiple choice question (MCQ) examinations, recently introduced in certain medical schools in this country, is decribed. The scheme allows for the variation of marks allocated to different in the paper, depending upon the relevance, importance and degree of difficulty of each question. However, the manner in which this new system is being implemented in some cases transgresses some fundamental principles of MCQ examinations. The consequence of this is that the average mark for the class is unintentionally low, with the good students separated from the main body of the class by a disproportionate number of marks. In addition, the examination lends itself to abuse by the enterprising student who is familar with the system of mark allocation."} {"id": "PMID:1265555", "title": "Clinical aspects of monocomponent insulins in the treatment of diabetes.", "content": "Conventional insulins, even if recrystallised many times, are found to contain several peptides on gel electrophoresis and are immunogenic. Antibody formation, insulin allergy, fat atrophy, fat hypertrophy and insulin bumps are thought to be largely caused by the impurities rather than by the insulin itself. 'Monocomponent' insulin has recently been prepared in the laboratories of Novo industries Ltd. Theoretically, this insulin should not cause the above complications. A combined clinical trial of monocomponent insulin has been carried out in Johannesburg and Cape Town on 24 patients with diabetes of diverse aetiology, who required insulin. The results of the trial may be summarised as follows: Monocomponent insulin appears to be very effective in patients with insulin allergy, adipopathy, and possibily in some patients in whom diabetes is not controlled with large doses of insulin. The monocomponent insulins deteriorate on storage at room temperature and yield monodesamido insulin. This de-amidation may be associated with persistent circulating antibodies to insulin and pro-insulin and with failure to reduce insulin requirements, but does not interfere with improvement in allergy or adipopathy. Long-standing diabetic patients, who are qell controlled with conventional insulin, are unlikely to gain therapeutic benefit from monocomponent insulin, and may even deteriorate or lose smooth metabolic control.", "contents": "Clinical aspects of monocomponent insulins in the treatment of diabetes. Conventional insulins, even if recrystallised many times, are found to contain several peptides on gel electrophoresis and are immunogenic. Antibody formation, insulin allergy, fat atrophy, fat hypertrophy and insulin bumps are thought to be largely caused by the impurities rather than by the insulin itself. 'Monocomponent' insulin has recently been prepared in the laboratories of Novo industries Ltd. Theoretically, this insulin should not cause the above complications. A combined clinical trial of monocomponent insulin has been carried out in Johannesburg and Cape Town on 24 patients with diabetes of diverse aetiology, who required insulin. The results of the trial may be summarised as follows: Monocomponent insulin appears to be very effective in patients with insulin allergy, adipopathy, and possibily in some patients in whom diabetes is not controlled with large doses of insulin. The monocomponent insulins deteriorate on storage at room temperature and yield monodesamido insulin. This de-amidation may be associated with persistent circulating antibodies to insulin and pro-insulin and with failure to reduce insulin requirements, but does not interfere with improvement in allergy or adipopathy. Long-standing diabetic patients, who are qell controlled with conventional insulin, are unlikely to gain therapeutic benefit from monocomponent insulin, and may even deteriorate or lose smooth metabolic control."} {"id": "PMID:1265556", "title": "Multiple colonic stricture formation and amoebiasis. A case report.", "content": "Case reports of multiple colonic strictures resulting from amoebiasis are uncommon in the literature. Such a case is presented and the diagnosis and management are discussed.", "contents": "Multiple colonic stricture formation and amoebiasis. A case report. Case reports of multiple colonic strictures resulting from amoebiasis are uncommon in the literature. Such a case is presented and the diagnosis and management are discussed."} {"id": "PMID:1265557", "title": "Sideroblastic anaemia associated with iron overload treated by repeated phlebotomy.", "content": "Iron overload with prominent skin pigmentation and hepatic parenchymal siderosis is reported in a patient with refractory sideroblastic anaemia. Failure to reverse the sideroblastic changes or the anaemia with conventional therapy prompted us to use a graded phlebotomy programme. The rising haemoglobin level in spite of repeated venesections is support for this approach in selected patients with this diagnosis.", "contents": "Sideroblastic anaemia associated with iron overload treated by repeated phlebotomy. Iron overload with prominent skin pigmentation and hepatic parenchymal siderosis is reported in a patient with refractory sideroblastic anaemia. Failure to reverse the sideroblastic changes or the anaemia with conventional therapy prompted us to use a graded phlebotomy programme. The rising haemoglobin level in spite of repeated venesections is support for this approach in selected patients with this diagnosis."} {"id": "PMID:1265561", "title": "Dissecting aneurysm of the aorta. A report of four cases.", "content": "Four cases of dissecting aneurysm of the aorta are discussed. The clinical diagnosis depends on awareness, suspicion, an association of certain preceding conditions and an understanding of the varied manifestations. Sudden, sharp chest pain, aortic valvar involvement and peripheral arterial occlusion are practically diagnostic. A widening of the aortic arch, the exclusion of myocardial infarction electrocardiographically, and an aortogram are helpful in the diagnosis. A dissecting aneurysm of the aorta is an emergency requiring early diagnosis and surgical treatment to improve the survival rate of 10%. Medical treatment is to be preferred for the chronic type of dissection.", "contents": "Dissecting aneurysm of the aorta. A report of four cases. Four cases of dissecting aneurysm of the aorta are discussed. The clinical diagnosis depends on awareness, suspicion, an association of certain preceding conditions and an understanding of the varied manifestations. Sudden, sharp chest pain, aortic valvar involvement and peripheral arterial occlusion are practically diagnostic. A widening of the aortic arch, the exclusion of myocardial infarction electrocardiographically, and an aortogram are helpful in the diagnosis. A dissecting aneurysm of the aorta is an emergency requiring early diagnosis and surgical treatment to improve the survival rate of 10%. Medical treatment is to be preferred for the chronic type of dissection."} {"id": "PMID:1265562", "title": "Alcohol, aspirin, depression, smoking, stress and the patient with a gastric ulcer.", "content": "It would seem that a gastric ulcer is the product of an interaction between chronic gastritis, the acid (and pepsin) of the gastric juice, and one or more precipitating factors. In a group of 194 consecutive patients with gastric ulceration particular note was made of whether they smoked, drank alcohol, used salicylates, were depressed or had experienced recent stress. There was an extraordinarily high incidence of depression among White women.", "contents": "Alcohol, aspirin, depression, smoking, stress and the patient with a gastric ulcer. It would seem that a gastric ulcer is the product of an interaction between chronic gastritis, the acid (and pepsin) of the gastric juice, and one or more precipitating factors. In a group of 194 consecutive patients with gastric ulceration particular note was made of whether they smoked, drank alcohol, used salicylates, were depressed or had experienced recent stress. There was an extraordinarily high incidence of depression among White women."} {"id": "PMID:1265563", "title": "Personal experience.", "content": "Three attacks of infective endocarditis with consequent emergency surgery to the aortic and mitral valves leave their mark. These are the impressions of a physician at the receiving end of his medical environment, an experience which entailed 4 periods of hospitalisation in 2 hospitals.", "contents": "Personal experience. Three attacks of infective endocarditis with consequent emergency surgery to the aortic and mitral valves leave their mark. These are the impressions of a physician at the receiving end of his medical environment, an experience which entailed 4 periods of hospitalisation in 2 hospitals."} {"id": "PMID:1265564", "title": "Onchocerciasis and the skin.", "content": "In areas of low prevalence of onchocerciasis, and in persons with low intensities of infection, the skin manifastations are of more frequent occurrence and of greater importance than the ocular complications. In addition to pruritus and erythema around the site of the bites, depigmentation of characteristic appearance is common.", "contents": "Onchocerciasis and the skin. In areas of low prevalence of onchocerciasis, and in persons with low intensities of infection, the skin manifastations are of more frequent occurrence and of greater importance than the ocular complications. In addition to pruritus and erythema around the site of the bites, depigmentation of characteristic appearance is common."} {"id": "PMID:1265565", "title": "Plasma cholinesterase variants - an unexpectedly high incidence of the silent allele.", "content": "The silent allele is one of the rarer plasma cholinesterase variants. In a series of 9 South African families with an inherited abnormal cholinesterase, the silent allele occurs in 5. In 2 it is the only abnormal allele present while in 3 it occurs with the 'atypical' (dibucaine-resistant) form. Identification of the single silent allele requires full family studies, since its inhibition characteristics are those of the other allele present, normal or abnormal.", "contents": "Plasma cholinesterase variants - an unexpectedly high incidence of the silent allele. The silent allele is one of the rarer plasma cholinesterase variants. In a series of 9 South African families with an inherited abnormal cholinesterase, the silent allele occurs in 5. In 2 it is the only abnormal allele present while in 3 it occurs with the 'atypical' (dibucaine-resistant) form. Identification of the single silent allele requires full family studies, since its inhibition characteristics are those of the other allele present, normal or abnormal."} {"id": "PMID:1265567", "title": "The isolation of Botryodiplodia theobromae from a nail lesion.", "content": "Botryodiplodia theobromae not known to produce onychomycosis was repeatedly recovered from a healthy woman with evident lesions in a toe nail. Mycelial fragments were observed in the scales and the fungus was isolated in cycloheximide-free culture media. The report indicates that many fungi, hitherto considered non-pathogens, may still be able to colonize a vaiety of human tissues.", "contents": "The isolation of Botryodiplodia theobromae from a nail lesion. Botryodiplodia theobromae not known to produce onychomycosis was repeatedly recovered from a healthy woman with evident lesions in a toe nail. Mycelial fragments were observed in the scales and the fungus was isolated in cycloheximide-free culture media. The report indicates that many fungi, hitherto considered non-pathogens, may still be able to colonize a vaiety of human tissues."} {"id": "PMID:1265568", "title": "Freeze-fracture replication of cultured Pityrosporum orbiculare.", "content": "Skin scrapings from a patient with Pityriasis versicolor were plated on a bile salt medium containing 10% glycerol (for cryoprotection) and Pityrosporum orbiculare was harvested for freeze-fracture replication. Resting and budding cells were senn. The overall pattern of indentation of the plasma membrane towards the cytoplasm was well revealed as a spiral arrangement of major indentations with minor ones disposed more or less at right angles. Hexagonally-arranged particles were not observed. Mitochondria were elongated with constrictions at intervals, and the fracture face of the limiting membrane directed towards the exterior exhibited linear arrays of particles. An unusual type of organelle was also present, viz: a membrane-limited vesicle with regularly-spaced depressions or \"dimples\".", "contents": "Freeze-fracture replication of cultured Pityrosporum orbiculare. Skin scrapings from a patient with Pityriasis versicolor were plated on a bile salt medium containing 10% glycerol (for cryoprotection) and Pityrosporum orbiculare was harvested for freeze-fracture replication. Resting and budding cells were senn. The overall pattern of indentation of the plasma membrane towards the cytoplasm was well revealed as a spiral arrangement of major indentations with minor ones disposed more or less at right angles. Hexagonally-arranged particles were not observed. Mitochondria were elongated with constrictions at intervals, and the fracture face of the limiting membrane directed towards the exterior exhibited linear arrays of particles. An unusual type of organelle was also present, viz: a membrane-limited vesicle with regularly-spaced depressions or \"dimples\"."} {"id": "PMID:1265569", "title": "In vivo development of spores of Absidia ramosa.", "content": "Approximately 10(6) spores of Absidia ramosa were inoculated intravenously into normal and cortisone pretreated mice. At subsequent time intervals the liver, lungs and kidneys were removed and examined for fungal localization and growth. In normal mice, spore germination and continued hyphal growth was restricted to the kidneys-evidence of germination not being visible until around 30h post inoculation. Cortisone therapy allowed germination of spores in the lung and kidney by 7h but subsequent hyphal growth in the lung was severely restricted compared with the kidney where extensive hyphal growth occurred. Germination of spores in the liver of cortisone treated animals was slow, not becoming apparent until about 40h after inoculation. These results suggest that host defence mechanisms in the form of phagocytosis as well as biochemical inhibitors and/or lack of suitable stimulators are important in preventing germination of introduced fungal spores. Once germination has occurred, it appears that additional as yet undetermined factors play a role in allowing continued growth of the fungus.", "contents": "In vivo development of spores of Absidia ramosa. Approximately 10(6) spores of Absidia ramosa were inoculated intravenously into normal and cortisone pretreated mice. At subsequent time intervals the liver, lungs and kidneys were removed and examined for fungal localization and growth. In normal mice, spore germination and continued hyphal growth was restricted to the kidneys-evidence of germination not being visible until around 30h post inoculation. Cortisone therapy allowed germination of spores in the lung and kidney by 7h but subsequent hyphal growth in the lung was severely restricted compared with the kidney where extensive hyphal growth occurred. Germination of spores in the liver of cortisone treated animals was slow, not becoming apparent until about 40h after inoculation. These results suggest that host defence mechanisms in the form of phagocytosis as well as biochemical inhibitors and/or lack of suitable stimulators are important in preventing germination of introduced fungal spores. Once germination has occurred, it appears that additional as yet undetermined factors play a role in allowing continued growth of the fungus."} {"id": "PMID:1265571", "title": "Animal ringworm in upper Egypt.", "content": "One thousand nine hundred and twenty animals (cattle, buffalo and sheep) and 60 humans suspected of ringworm were investigated in Egypt. Clinical and mycological aspects of the disease are described. Trichophyton verrucosum was the commonest dermatophyter on all species examined. Only T. mentagrophytes was isolated once from soil in the region of the clinical cases.", "contents": "Animal ringworm in upper Egypt. One thousand nine hundred and twenty animals (cattle, buffalo and sheep) and 60 humans suspected of ringworm were investigated in Egypt. Clinical and mycological aspects of the disease are described. Trichophyton verrucosum was the commonest dermatophyter on all species examined. Only T. mentagrophytes was isolated once from soil in the region of the clinical cases."} {"id": "PMID:1265572", "title": "Cutaneous geotrichosis in the red flamingo (Phoenicopterus ruber).", "content": "In three flamingos (Phoenicopterus ruber), which died showing extensive necrotic inflammation of the skin of the webs and the legs, the presence of abundant mycelium and arthrospores was shown in the altered dermis and epidermis. From all the lesions Geotrichum Candidum was isolated in pure culture. Inoculation of suspensions of the fungus into domestic chickens and mice produced granulomas or more purulent nodules with central growth of abundant mycelium. From 20 of 28 experimental animals, G. candidum was reisolated from the lesions in pure culture 2 weeks after the inoculation. It is suggested that alteration of the skin by e.g., prolonged contact with pondwater, the presence of small wounds and the advanced age of the birds, acting as predisposing factors may be necessary in establishing this disease.", "contents": "Cutaneous geotrichosis in the red flamingo (Phoenicopterus ruber). In three flamingos (Phoenicopterus ruber), which died showing extensive necrotic inflammation of the skin of the webs and the legs, the presence of abundant mycelium and arthrospores was shown in the altered dermis and epidermis. From all the lesions Geotrichum Candidum was isolated in pure culture. Inoculation of suspensions of the fungus into domestic chickens and mice produced granulomas or more purulent nodules with central growth of abundant mycelium. From 20 of 28 experimental animals, G. candidum was reisolated from the lesions in pure culture 2 weeks after the inoculation. It is suggested that alteration of the skin by e.g., prolonged contact with pondwater, the presence of small wounds and the advanced age of the birds, acting as predisposing factors may be necessary in establishing this disease."} {"id": "PMID:1265573", "title": "Cutaneous infection of a porcupine (Erethizon dorsatum) by Aureobasidium pullulans.", "content": "Aureobasidium pullulans was repeatedly isolated from a cutaneous infection of a porcupine (Erethizon dorsatum). Tissue sections revealed fungal filaments similar to those of A. pullulans. This is the first reported association of A. pullulans with a natural infection of either wild or domesticated animals.", "contents": "Cutaneous infection of a porcupine (Erethizon dorsatum) by Aureobasidium pullulans. Aureobasidium pullulans was repeatedly isolated from a cutaneous infection of a porcupine (Erethizon dorsatum). Tissue sections revealed fungal filaments similar to those of A. pullulans. This is the first reported association of A. pullulans with a natural infection of either wild or domesticated animals."} {"id": "PMID:1265574", "title": "Pemphigus vulgaris and disseminated coccidioidomycosis.", "content": "A Mexican-American patient with pemphigus vulgaris developed fatal disseminated coccidioidomycosis while on immunosuppressive therapy with systemic corticosteroids and azathioprine. Immunosuppressed patients should be carefully monitored for coccidioidomycosis as well as other systemic mycoses.", "contents": "Pemphigus vulgaris and disseminated coccidioidomycosis. A Mexican-American patient with pemphigus vulgaris developed fatal disseminated coccidioidomycosis while on immunosuppressive therapy with systemic corticosteroids and azathioprine. Immunosuppressed patients should be carefully monitored for coccidioidomycosis as well as other systemic mycoses."} {"id": "PMID:1265575", "title": "Pichia norvegensis sp. nov.", "content": "A new yeast species Pichia norvegensis Leask et Yarrow is described as the perfect state of Candida norvegensis (Dietrichson) van Uden et Farinha ex van Uden et Buckley. Strains of this species were isolated on 3 occasions from human vaginas. This species differs from other Pichia species that assimilate glucose but not galactose, sucrose, maltose, lactose, D-mannitol and D-glucitol by assimilating cellobiose.", "contents": "Pichia norvegensis sp. nov. A new yeast species Pichia norvegensis Leask et Yarrow is described as the perfect state of Candida norvegensis (Dietrichson) van Uden et Farinha ex van Uden et Buckley. Strains of this species were isolated on 3 occasions from human vaginas. This species differs from other Pichia species that assimilate glucose but not galactose, sucrose, maltose, lactose, D-mannitol and D-glucitol by assimilating cellobiose."} {"id": "PMID:1265576", "title": "Light resistance in geophilic dermatophytes.", "content": "The effect of repeated illumination by ultraviolet or visible light on slide cultures of Trichophyton ajelloi and Microporum cookei was studied. Under UV light, germination was inhibited, spores were damaged and destroyed, growth was suppressed and the hyphae were killed. Inhibition was dependent on exposure time and wavelength. Lethal doses for the far UV range were as high as 1 300-1 700 mW sec/cm2 for T. ajelloi and 2 300 mW sec/cm2 for M. cookei. The same effect was caused by the complete UV region but the far UV range was most effective. One exposure, however long, was not sufficient to kill the inoculum but this was effected by smaller doses when repeated 4 times at daily intervals. Under visible light, germination of the spores and growth of the young hyphae were inhibited. Depending on the exposure time and wavelength used, inhibition of 8 to 76% of controls grown in darkness were noted. The inhibition degree was increased up to lethality when the mycelium was sensitized by means of eosin. The coefficient of variation increased regularly up to very high values following exposures to sublethal doses of light...", "contents": "Light resistance in geophilic dermatophytes. The effect of repeated illumination by ultraviolet or visible light on slide cultures of Trichophyton ajelloi and Microporum cookei was studied. Under UV light, germination was inhibited, spores were damaged and destroyed, growth was suppressed and the hyphae were killed. Inhibition was dependent on exposure time and wavelength. Lethal doses for the far UV range were as high as 1 300-1 700 mW sec/cm2 for T. ajelloi and 2 300 mW sec/cm2 for M. cookei. The same effect was caused by the complete UV region but the far UV range was most effective. One exposure, however long, was not sufficient to kill the inoculum but this was effected by smaller doses when repeated 4 times at daily intervals. Under visible light, germination of the spores and growth of the young hyphae were inhibited. Depending on the exposure time and wavelength used, inhibition of 8 to 76% of controls grown in darkness were noted. The inhibition degree was increased up to lethality when the mycelium was sensitized by means of eosin. The coefficient of variation increased regularly up to very high values following exposures to sublethal doses of light..."} {"id": "PMID:1265577", "title": "Antibiotic sensitivity of the yeast and mycelial phases of Histoplasma capsulatum.", "content": "Cycloheximide and chloramphenicol in combination have a greater effect on yeast cells of Histoplasma capsulatum than on the mycelial phase of this fungus. In contrast, clotrimazole was found to be more effective against mycelia. Miconazole produced a pronounced effect against both phases wheras tolnaftate was only slightly active. Sulfadiazine and griseofulvin were completely inactive against both phases. The differential sensitivities of the 2 phases of H. capsulatum to various antibiotics can be useful in studying the transition of the dimorphic fungus from 1 phase to the other.", "contents": "Antibiotic sensitivity of the yeast and mycelial phases of Histoplasma capsulatum. Cycloheximide and chloramphenicol in combination have a greater effect on yeast cells of Histoplasma capsulatum than on the mycelial phase of this fungus. In contrast, clotrimazole was found to be more effective against mycelia. Miconazole produced a pronounced effect against both phases wheras tolnaftate was only slightly active. Sulfadiazine and griseofulvin were completely inactive against both phases. The differential sensitivities of the 2 phases of H. capsulatum to various antibiotics can be useful in studying the transition of the dimorphic fungus from 1 phase to the other."} {"id": "PMID:1265598", "title": "Congenital posterolateral diaphragmatic hernia.", "content": "The infant who is born with a posterolateral diaphragmatic hernia who becomes symptomatic at or soon after birth requires urgent care. Surgical reduction of the diaphragmatic hernia must be accomplished quickly. Respiratory and metabolic acidosis must be treated appropriately. The parents should be informed of the gravity of their infant's problem and reassurred by appropriate explanation of the nature of the defect and the therapeutic requirements. If the infant dies, the parents are in need of empathy, reassurance, and adequate explanation so that they do not have lingering doubts regarding the etiology of the anomaly and the adequacy of the therapy. If the infant lives, the medical team can share the feeling of a job well done.", "contents": "Congenital posterolateral diaphragmatic hernia. The infant who is born with a posterolateral diaphragmatic hernia who becomes symptomatic at or soon after birth requires urgent care. Surgical reduction of the diaphragmatic hernia must be accomplished quickly. Respiratory and metabolic acidosis must be treated appropriately. The parents should be informed of the gravity of their infant's problem and reassurred by appropriate explanation of the nature of the defect and the therapeutic requirements. If the infant dies, the parents are in need of empathy, reassurance, and adequate explanation so that they do not have lingering doubts regarding the etiology of the anomaly and the adequacy of the therapy. If the infant lives, the medical team can share the feeling of a job well done."} {"id": "PMID:1265600", "title": "Hirschsprung's disease.", "content": "Hirschsprung's disease or aganglionic megacolon is an anomaly caused by the absence of ganglion cells in the myenteric plexus of the distal colon. It produces intestinal obstruction or lethal enterocolitis in the neonatal period and constipation of varying degree in the older child. The diagnosis can be made by history alone and confirmed by physical findings, barium enema, motility studies, and rectal biopsy. Colostomy may be a life saving measure in the newborn, to be followed by a definitive pull-through procedure before the age of 1 year. Operative correction consists of various techniques all of which aim for excision of the aganglionic segment with preservation of the internal anal sphincter. The major pitfall of these procedures is a too perfectly preserved sphincter which remains spastic and still produces obstruction. Some damage to this muscle must be accomplished either during the procedure or postoperatively by bouginage in order to obtain a satisfactory result.", "contents": "Hirschsprung's disease. Hirschsprung's disease or aganglionic megacolon is an anomaly caused by the absence of ganglion cells in the myenteric plexus of the distal colon. It produces intestinal obstruction or lethal enterocolitis in the neonatal period and constipation of varying degree in the older child. The diagnosis can be made by history alone and confirmed by physical findings, barium enema, motility studies, and rectal biopsy. Colostomy may be a life saving measure in the newborn, to be followed by a definitive pull-through procedure before the age of 1 year. Operative correction consists of various techniques all of which aim for excision of the aganglionic segment with preservation of the internal anal sphincter. The major pitfall of these procedures is a too perfectly preserved sphincter which remains spastic and still produces obstruction. Some damage to this muscle must be accomplished either during the procedure or postoperatively by bouginage in order to obtain a satisfactory result."} {"id": "PMID:1265601", "title": "Omphalocele.", "content": "From a historical curiosity at the turn of the century, today omphalocele and gastroschisis can be corrected with good results, thanks to innovative techniques and better understanding of the newborn. Associated anomalies consist mainly of malrotation, Meckel's diverticulum, intestinal atresia, congenital heart defects, and genitourinary abnormalities. Nonoperative management in certain centers has been sucessful for the very large omphaloceles with an intact sac; however, a secondary procedure is necessary. In the past 10 years, the use of Silastic sheeting and total parenteral nutrition has allowed early repair of even the most severe cases, with excellent end results and low mortality.", "contents": "Omphalocele. From a historical curiosity at the turn of the century, today omphalocele and gastroschisis can be corrected with good results, thanks to innovative techniques and better understanding of the newborn. Associated anomalies consist mainly of malrotation, Meckel's diverticulum, intestinal atresia, congenital heart defects, and genitourinary abnormalities. Nonoperative management in certain centers has been sucessful for the very large omphaloceles with an intact sac; however, a secondary procedure is necessary. In the past 10 years, the use of Silastic sheeting and total parenteral nutrition has allowed early repair of even the most severe cases, with excellent end results and low mortality."} {"id": "PMID:1265603", "title": "Imperforate anus.", "content": "Sucessful treatment of the child with imperforate anus yields an individual with satisfactory continence and a healthy urinary tract. These goals are achieved by accurate evaluation of the newborn, optimal technical results, and conscientious follow-up. The infant born with one of these malformations frequently has a serious associated anomaly which also requires early specific diagnosis and management. When the bowel has passed through the puborectalis in utero, the deformity can often be definitively treated in the neonate by dilations or anoplasty. However, if a urinary or high vaginal fistula is present, or if the anomaly is of the supralevator type, definitive surgery is best postponed some months and the neonate given a colostomy. We have found the sacroabdominoperitoneal approach to be the most satisfactory pullthrough procedure for the supralevator lesion. The children with high, supralevator anomalies have higher mortality rates and, in one out of four cases, have suboptimal fecal continence. They require the utmost in technical skill and continuing care if they are to lives free of social stigma. The mortality rate in all other types is low and the functional continence uniformly acceptable.", "contents": "Imperforate anus. Sucessful treatment of the child with imperforate anus yields an individual with satisfactory continence and a healthy urinary tract. These goals are achieved by accurate evaluation of the newborn, optimal technical results, and conscientious follow-up. The infant born with one of these malformations frequently has a serious associated anomaly which also requires early specific diagnosis and management. When the bowel has passed through the puborectalis in utero, the deformity can often be definitively treated in the neonate by dilations or anoplasty. However, if a urinary or high vaginal fistula is present, or if the anomaly is of the supralevator type, definitive surgery is best postponed some months and the neonate given a colostomy. We have found the sacroabdominoperitoneal approach to be the most satisfactory pullthrough procedure for the supralevator lesion. The children with high, supralevator anomalies have higher mortality rates and, in one out of four cases, have suboptimal fecal continence. They require the utmost in technical skill and continuing care if they are to lives free of social stigma. The mortality rate in all other types is low and the functional continence uniformly acceptable."} {"id": "PMID:1265605", "title": "A clinicopathologic study of hepatic dysfunction following shock.", "content": "Nineteen patients who had profound hypotensive shock were studied to correlate the light and electron microscopic appearances of the liver with the clinical and biochemical evidence of hepatic dysfunction. Despite the multiple etiologic factors that can result in jaundice in these patients, a fluctuating pattern occurs which enables the correlation of a bilirubin peak with the predominating etiologic factor. Immediately after shock, there was enzymatic and light and electron microscopic evidence of hepatocellular damage, resulting in a jaundice peak on the eighth to tenth day after the shock episode. This was followed by repair and regeneration of the liver as well as an increase in cholestatic enzyme levels. Later, bilirubin peaks occurred when hepatocellular function was further decreased or overloaded against this background of dysfunction related to the episode of shock. Recovery of hepatic function could continue or be delayed by intercurrent disease, particularly systemic infection. Support of hepatic function, similar to that available for pulmonary and renal failure may, in the future, be used to effect the prognosis of these patients.", "contents": "A clinicopathologic study of hepatic dysfunction following shock. Nineteen patients who had profound hypotensive shock were studied to correlate the light and electron microscopic appearances of the liver with the clinical and biochemical evidence of hepatic dysfunction. Despite the multiple etiologic factors that can result in jaundice in these patients, a fluctuating pattern occurs which enables the correlation of a bilirubin peak with the predominating etiologic factor. Immediately after shock, there was enzymatic and light and electron microscopic evidence of hepatocellular damage, resulting in a jaundice peak on the eighth to tenth day after the shock episode. This was followed by repair and regeneration of the liver as well as an increase in cholestatic enzyme levels. Later, bilirubin peaks occurred when hepatocellular function was further decreased or overloaded against this background of dysfunction related to the episode of shock. Recovery of hepatic function could continue or be delayed by intercurrent disease, particularly systemic infection. Support of hepatic function, similar to that available for pulmonary and renal failure may, in the future, be used to effect the prognosis of these patients."} {"id": "PMID:1265606", "title": "Fecaloma simulating colonic neoplasm.", "content": "Large, discrete fecal masses in the colon may be confused with neoplasms, particularly if they are relatively immobile. The radiologic features of such masses generally permit their true identification.", "contents": "Fecaloma simulating colonic neoplasm. Large, discrete fecal masses in the colon may be confused with neoplasms, particularly if they are relatively immobile. The radiologic features of such masses generally permit their true identification."} {"id": "PMID:1265607", "title": "Laboratory observations and clinical implications of monitoring the effect of heparin by bioassay.", "content": "Laboratory and clinical experience in the monitoring of circulating heparin concentration of bioassay shows that the whole blood clotting time and the activated partial thromboplastin time differ in their reflection of the state of anticoagulation. The decay of biologic activity may be as short as 30 minutes in one patient or as long as 360 minutes in another. This fact may drastically affect patient response to the drug. Safe and rational clinical heparinization is dependent upon periodic monitoring of the circulating heparin concentration. The success of this method was illustrated in two representative patients.", "contents": "Laboratory observations and clinical implications of monitoring the effect of heparin by bioassay. Laboratory and clinical experience in the monitoring of circulating heparin concentration of bioassay shows that the whole blood clotting time and the activated partial thromboplastin time differ in their reflection of the state of anticoagulation. The decay of biologic activity may be as short as 30 minutes in one patient or as long as 360 minutes in another. This fact may drastically affect patient response to the drug. Safe and rational clinical heparinization is dependent upon periodic monitoring of the circulating heparin concentration. The success of this method was illustrated in two representative patients."} {"id": "PMID:1265608", "title": "The pathogenesis of diarrhea after bypass of the small intestine.", "content": "Certain aspects of the pathogenesis of the diarrhea after bypass procedures of the small intestine for obesity have been evaluated. In the late postoperative period, a significant increase occurred in fecal weight and in fecal bile salt and free fatty acid output. There was a significant direct correlation between fecal weight and fecal bile salt output. There was no significant correlation between fecal weight and fecal fatty acid output. This suggests that, after bypass procedures of the small intestine, bile salts play a more significant role in the pathogenesis of diarrhea than do free fatty acids.", "contents": "The pathogenesis of diarrhea after bypass of the small intestine. Certain aspects of the pathogenesis of the diarrhea after bypass procedures of the small intestine for obesity have been evaluated. In the late postoperative period, a significant increase occurred in fecal weight and in fecal bile salt and free fatty acid output. There was a significant direct correlation between fecal weight and fecal bile salt output. There was no significant correlation between fecal weight and fecal fatty acid output. This suggests that, after bypass procedures of the small intestine, bile salts play a more significant role in the pathogenesis of diarrhea than do free fatty acids."} {"id": "PMID:1265609", "title": "Genetic heterogeneity and familial carcinoma of the breast.", "content": "The particular patterns of familial aggregations of cancer in the several families reported from our clinical resource suggest that multiple genotypes explain their diversity of cancer susceptibility. This knowledge could be of value in improving cancer control. We postulate that each particular genotype functions in concert with differential carcinogenic interactions, including a possible oncogenic virus, contributing to carcinogenesis in the susceptible patient. This reasoning is consistent with a concept of genetic heterogeneity as an explanation for familial carcinoma of the breast. This phenomenon is not unlike the current explanation for the genetics of the mucopolysaccaridoses, the lipidoses and several other major disorders of man which show genetic heterogeneity.", "contents": "Genetic heterogeneity and familial carcinoma of the breast. The particular patterns of familial aggregations of cancer in the several families reported from our clinical resource suggest that multiple genotypes explain their diversity of cancer susceptibility. This knowledge could be of value in improving cancer control. We postulate that each particular genotype functions in concert with differential carcinogenic interactions, including a possible oncogenic virus, contributing to carcinogenesis in the susceptible patient. This reasoning is consistent with a concept of genetic heterogeneity as an explanation for familial carcinoma of the breast. This phenomenon is not unlike the current explanation for the genetics of the mucopolysaccaridoses, the lipidoses and several other major disorders of man which show genetic heterogeneity."} {"id": "PMID:1265610", "title": "Arteriovenous fistulas for dialysis using modified bovine arteries.", "content": "Arteriovenous fistulas were created on 21 occasions in 18 patients using an interposed segment of processed bovine carotid artery. In 18 fistulas, there were loops in the femoral region, and in three, they were created in the forearm. Seventeen of 21 fistulas developed a useful patency, with useful patency being achieved in 16 of the 18 patients. This patency is impressive, since it provided life-saving vascular access in these patients who previously had had failure of multiple standard shunts or fistulas. However, there was a high incidence of complications, with 17 of 21 fistulas developing some complication. Ten fistulas spontaneously occluded, but flow was restored in six. Seven significant infections occurred in fistulas of the thigh, with one patient eventually dying from complications. In two patients, major hematomas developed, and in six patients, false aneurysms developed, four of these false aneurysms being clearly associated with infection. Venograms were useful in the arm for demonstrating patency of the vein to be used for the arteriovenous fistula. The bovine interposed segment is a useful alternative in patients with difficult vascular access problems for hemodialysis but should be reserved only for such patients.", "contents": "Arteriovenous fistulas for dialysis using modified bovine arteries. Arteriovenous fistulas were created on 21 occasions in 18 patients using an interposed segment of processed bovine carotid artery. In 18 fistulas, there were loops in the femoral region, and in three, they were created in the forearm. Seventeen of 21 fistulas developed a useful patency, with useful patency being achieved in 16 of the 18 patients. This patency is impressive, since it provided life-saving vascular access in these patients who previously had had failure of multiple standard shunts or fistulas. However, there was a high incidence of complications, with 17 of 21 fistulas developing some complication. Ten fistulas spontaneously occluded, but flow was restored in six. Seven significant infections occurred in fistulas of the thigh, with one patient eventually dying from complications. In two patients, major hematomas developed, and in six patients, false aneurysms developed, four of these false aneurysms being clearly associated with infection. Venograms were useful in the arm for demonstrating patency of the vein to be used for the arteriovenous fistula. The bovine interposed segment is a useful alternative in patients with difficult vascular access problems for hemodialysis but should be reserved only for such patients."} {"id": "PMID:1265611", "title": "Noninvasive prevention of thrombosis of deep veins of the thigh using intermittent pneumatic compression.", "content": "Intermitten venous compression promotes cyclic emptying and refilling of the veins and sinuses of the legs. It prevents stasis and formation of thrombi while the patient is on the operating table and during recovery. Once the patient is ambulatory, the system is discontinued. While the system is in use, thromboelastography, venous impedance plethysmography and venography, when indicated, are used to monitor the system. The intermittent pneumatic compression system is safe, simple and practical to use for almost all patients. There was no evidence of deep vein thrombosis or pulmonary embolism in 123 patients, as determined by an absence of clinical signs, a negative impedance plethysmogram and a negative venogram.", "contents": "Noninvasive prevention of thrombosis of deep veins of the thigh using intermittent pneumatic compression. Intermitten venous compression promotes cyclic emptying and refilling of the veins and sinuses of the legs. It prevents stasis and formation of thrombi while the patient is on the operating table and during recovery. Once the patient is ambulatory, the system is discontinued. While the system is in use, thromboelastography, venous impedance plethysmography and venography, when indicated, are used to monitor the system. The intermittent pneumatic compression system is safe, simple and practical to use for almost all patients. There was no evidence of deep vein thrombosis or pulmonary embolism in 123 patients, as determined by an absence of clinical signs, a negative impedance plethysmogram and a negative venogram."} {"id": "PMID:1265612", "title": "Arterial endothelial changes after ischemia and perfusion.", "content": "The effects of six hours of ischemia and six hours of perfusion with 10 per cent dextrose and water solution, Sacks' solution and Intralipid on the endothelium of common femoral arteries in dogs were examined by light and by scanning electron microscopy and compared with normal arteries. Arteries that were ischemic or perfused with 10 per cent dextrose and water solution or Sacks' solution showed a flattening of the normal linear convolutions and extensive crater formation, with fragmentation and even complete loss of endothelial cells in many areas. The more severe changes occurred in perfused vessels. Fibrin and platelets covered the luminal surface in many areas in which there was extensive injury to the endothelium. Light microscopy revealed thickening of the internal elastic membrane and intimal fibrosis. Results of biopsies performed two weeks after perfusion showed slight, although incomplete, improvement in the structure of the endothelium. Arteries perfused with Intralipid had thickening of the intima with a proliferation of plump cells orientd linearly over the surface but with an absence of craters. Results of present studies confirm the observations of other investigators that injury to endothelial cells may be produced by ischemia and that perfusion with various solutions may produce an even more severe alteration in structure of the endothelial cell which does not return to normal within two weeks. The origin of new endothelial cells is not demonstrated by this study.", "contents": "Arterial endothelial changes after ischemia and perfusion. The effects of six hours of ischemia and six hours of perfusion with 10 per cent dextrose and water solution, Sacks' solution and Intralipid on the endothelium of common femoral arteries in dogs were examined by light and by scanning electron microscopy and compared with normal arteries. Arteries that were ischemic or perfused with 10 per cent dextrose and water solution or Sacks' solution showed a flattening of the normal linear convolutions and extensive crater formation, with fragmentation and even complete loss of endothelial cells in many areas. The more severe changes occurred in perfused vessels. Fibrin and platelets covered the luminal surface in many areas in which there was extensive injury to the endothelium. Light microscopy revealed thickening of the internal elastic membrane and intimal fibrosis. Results of biopsies performed two weeks after perfusion showed slight, although incomplete, improvement in the structure of the endothelium. Arteries perfused with Intralipid had thickening of the intima with a proliferation of plump cells orientd linearly over the surface but with an absence of craters. Results of present studies confirm the observations of other investigators that injury to endothelial cells may be produced by ischemia and that perfusion with various solutions may produce an even more severe alteration in structure of the endothelial cell which does not return to normal within two weeks. The origin of new endothelial cells is not demonstrated by this study."} {"id": "PMID:1265613", "title": "Role of preoperative bone scan in carcinoma of the breast.", "content": "Although a skeletal scan is an effective means of detecting early metastatic deposits from carcinoma of the breast, its indiscriminate use in screening patients with early tumors does not seem justified because of the low yield of abnormal results. Selection of patients for this procedure should be based on the size of the tumor and the clinical stage of the disease. It is extremely unlikely that patients with a T1 lesion will have an abnormal skeletal scan. A preoperative scan in indicated for T2 lesions in patients with a central or medial quadrant mass, inflammatory carcinoma, palpable axillary lymph nodes or other clinical evidence suggestive of spread beyond breast tissue. All patients with T3 and inoperable tumors should have a bone scan prior to therapy to define the extent of the disease. A routine postoperative scan at six month intervals may be considered only in patients with large primary lesions and involvement of regional lymph nodes.", "contents": "Role of preoperative bone scan in carcinoma of the breast. Although a skeletal scan is an effective means of detecting early metastatic deposits from carcinoma of the breast, its indiscriminate use in screening patients with early tumors does not seem justified because of the low yield of abnormal results. Selection of patients for this procedure should be based on the size of the tumor and the clinical stage of the disease. It is extremely unlikely that patients with a T1 lesion will have an abnormal skeletal scan. A preoperative scan in indicated for T2 lesions in patients with a central or medial quadrant mass, inflammatory carcinoma, palpable axillary lymph nodes or other clinical evidence suggestive of spread beyond breast tissue. All patients with T3 and inoperable tumors should have a bone scan prior to therapy to define the extent of the disease. A routine postoperative scan at six month intervals may be considered only in patients with large primary lesions and involvement of regional lymph nodes."} {"id": "PMID:1265614", "title": "The coagulation and fibrinolytic response to splenectomy.", "content": "The responses of the coagulation and fibrinolytic systems in nine patients with Hodgkin's disease undergoing splenectomy and lymph node mapping have been compared with those in nine patients undergoing elective upper abdominal operation for benign conditions. Differences have been noted in base line levels of fibrinogen, prothrombin, partial thromboplastin time and euglobulin lysis time. Platelet count increases were exaggerated following splenectomy, but other parameters of coagulation activity behaved similarly in the two groups. There is no evidence from this study to support the suggestion that blood coagulability is increased more markedly following splenectomy than it is after other upper abdominal operations.", "contents": "The coagulation and fibrinolytic response to splenectomy. The responses of the coagulation and fibrinolytic systems in nine patients with Hodgkin's disease undergoing splenectomy and lymph node mapping have been compared with those in nine patients undergoing elective upper abdominal operation for benign conditions. Differences have been noted in base line levels of fibrinogen, prothrombin, partial thromboplastin time and euglobulin lysis time. Platelet count increases were exaggerated following splenectomy, but other parameters of coagulation activity behaved similarly in the two groups. There is no evidence from this study to support the suggestion that blood coagulability is increased more markedly following splenectomy than it is after other upper abdominal operations."} {"id": "PMID:1265615", "title": "Percutaneous biopsy of carcinoma of the pancreas guided by angiography.", "content": "Histologic verification of the angiographic diagnosis of carcinoma of the pancreas may be achieved by percutaneous, transperitoneal fine-needle aspiration biopsy. The method was used in conjunction with the angiographic procedure in 29 patients with tumors of varying size down to 3 centimeters in diameter. Positive diagnosis was obtained in 22. Complications were not encountered. Since the method is simple and harmless it is recommended whenever histologic verification is desired.", "contents": "Percutaneous biopsy of carcinoma of the pancreas guided by angiography. Histologic verification of the angiographic diagnosis of carcinoma of the pancreas may be achieved by percutaneous, transperitoneal fine-needle aspiration biopsy. The method was used in conjunction with the angiographic procedure in 29 patients with tumors of varying size down to 3 centimeters in diameter. Positive diagnosis was obtained in 22. Complications were not encountered. Since the method is simple and harmless it is recommended whenever histologic verification is desired."} {"id": "PMID:1265619", "title": "Experimental aneurysms.", "content": "Aneurysms were produced experimentally with vein patch grafts on the carotid artery in the neck in rats. Aneurysms created at the bifurcation of the common carotid artery had a greater tendency to enlarge than did those on the trunk of the common carotid artery. Four aneurysms on the carotid trunk thrombosed; none did so at the bifurcation. The aneurysms ruptured in nine cases, more often when they were covered with oxycell than when they were not. Experimental aneurysms were also produced on the middle cerebral arteries in dogs.", "contents": "Experimental aneurysms. Aneurysms were produced experimentally with vein patch grafts on the carotid artery in the neck in rats. Aneurysms created at the bifurcation of the common carotid artery had a greater tendency to enlarge than did those on the trunk of the common carotid artery. Four aneurysms on the carotid trunk thrombosed; none did so at the bifurcation. The aneurysms ruptured in nine cases, more often when they were covered with oxycell than when they were not. Experimental aneurysms were also produced on the middle cerebral arteries in dogs."} {"id": "PMID:1265620", "title": "Inhibition of cell-mediated immunity in patients with brain tumors.", "content": "The immunocompetence of patients with glioblastomas, but not patients with astrocytomas, is altered. In vitro testing demonstrates an inhibitory factor in the serum of patients with glioblastomas which impairs lymphocytic responsiveness. The degree of this impairment appears important in relation to the clinical course.", "contents": "Inhibition of cell-mediated immunity in patients with brain tumors. The immunocompetence of patients with glioblastomas, but not patients with astrocytomas, is altered. In vitro testing demonstrates an inhibitory factor in the serum of patients with glioblastomas which impairs lymphocytic responsiveness. The degree of this impairment appears important in relation to the clinical course."} {"id": "PMID:1265621", "title": "Hemicraniectomy in the treatment of acute subdural hematoma: a re-appraisal.", "content": "Although acute subdural hematoma continues to be one of the more common conditions neurosurgeons are called upon to treat, mortality rates continue to be quite unsatisfactory. Hemicraniectomy with wide decompression of the swollen brain was devised for the condition in 1971 (JNS 34:70-76). Initial results were quite encouraging with a 40% overall survival rate, 28% of the patients returning to normal activity. Since this original report, an additional 50 patients have been treated with only a 10% total survival rate and a 4% functional survival rate. Retrospective analysis of our cases over the past three years reveals that patient's age, status of preoperative neurologic examination, angiographic findings and appearance of the brain at operation, all have no statistical correlation with survival. These statistics will be presented and discussed. The failure of hemicraniectomy and extensive clot removal to significantly increase the functional survival rate in this condition implies that in a majority of patients with \"acute subdural hematoma,\" primary brain stem and possibly subcortical injury are present, neither of which is amenable to radical therapy. The operation of hemicraniectomy should be restricted to those patients who enter hospital, obtunded but without demonstrable brain stem dysfunctionn, only to deteriorate subsequently because of increasing hemispheric edema and/or subdural clot.", "contents": "Hemicraniectomy in the treatment of acute subdural hematoma: a re-appraisal. Although acute subdural hematoma continues to be one of the more common conditions neurosurgeons are called upon to treat, mortality rates continue to be quite unsatisfactory. Hemicraniectomy with wide decompression of the swollen brain was devised for the condition in 1971 (JNS 34:70-76). Initial results were quite encouraging with a 40% overall survival rate, 28% of the patients returning to normal activity. Since this original report, an additional 50 patients have been treated with only a 10% total survival rate and a 4% functional survival rate. Retrospective analysis of our cases over the past three years reveals that patient's age, status of preoperative neurologic examination, angiographic findings and appearance of the brain at operation, all have no statistical correlation with survival. These statistics will be presented and discussed. The failure of hemicraniectomy and extensive clot removal to significantly increase the functional survival rate in this condition implies that in a majority of patients with \"acute subdural hematoma,\" primary brain stem and possibly subcortical injury are present, neither of which is amenable to radical therapy. The operation of hemicraniectomy should be restricted to those patients who enter hospital, obtunded but without demonstrable brain stem dysfunctionn, only to deteriorate subsequently because of increasing hemispheric edema and/or subdural clot."} {"id": "PMID:1265622", "title": "Alcoholic cerebellar disease and seizures.", "content": "Forty-eight chronic alcoholic patients with a clinical picture consistent with midline cerebellar disease were evaluated regarding alcohol related seizures. These seizures were noted in about 15% of this patient group. This seizure incidence approximates that in the severely alcoholic hospitalized population. Thus, the midline cerebellar degeneration does not appear to influence the seizure diathesis in the chronic alcoholic.", "contents": "Alcoholic cerebellar disease and seizures. Forty-eight chronic alcoholic patients with a clinical picture consistent with midline cerebellar disease were evaluated regarding alcohol related seizures. These seizures were noted in about 15% of this patient group. This seizure incidence approximates that in the severely alcoholic hospitalized population. Thus, the midline cerebellar degeneration does not appear to influence the seizure diathesis in the chronic alcoholic."} {"id": "PMID:1265623", "title": "Complications of ventriculo-vascular shunts: computer analysis of etiological factors.", "content": "The charts were reviewed at 323 patients who underwent a total of 578 ventricular shunting procedures at the Vancouver General Hospital, the original procedure having been done between 1960 and 1970 inclusive. There were 503 ventriculoatrial shunts, 38 ventriculo-peritoneal shunts, 34 Torkildsen procedures and three other procedures. The complications of the 503 ventriculo-vascular shunts, and the technique variables that might be related to these complications, were subjected to computer analysis.", "contents": "Complications of ventriculo-vascular shunts: computer analysis of etiological factors. The charts were reviewed at 323 patients who underwent a total of 578 ventricular shunting procedures at the Vancouver General Hospital, the original procedure having been done between 1960 and 1970 inclusive. There were 503 ventriculoatrial shunts, 38 ventriculo-peritoneal shunts, 34 Torkildsen procedures and three other procedures. The complications of the 503 ventriculo-vascular shunts, and the technique variables that might be related to these complications, were subjected to computer analysis."} {"id": "PMID:1265624", "title": "Epidermoid of the fourth ventricle: discovery by computerized tomography.", "content": "A case of fourth ventricular epidermoid is presented. The initial diagnosis was considered to be multiple sclerosis. Computerized axial tomography demonstrated the lesion without enhancement. Since fourth ventricular epidermoids may present in a variety of ways, the value of computerized tomography is emphasized.", "contents": "Epidermoid of the fourth ventricle: discovery by computerized tomography. A case of fourth ventricular epidermoid is presented. The initial diagnosis was considered to be multiple sclerosis. Computerized axial tomography demonstrated the lesion without enhancement. Since fourth ventricular epidermoids may present in a variety of ways, the value of computerized tomography is emphasized."} {"id": "PMID:1265625", "title": "Carotid-ophthalmic aneurysms.", "content": "Carotid-ophthalmic aneurysms have intimate relationships with the ipsilateral optic nerve and other neighboring structures. Direct operation for treatment of these aneurysms has been considered particularly hazardous and difficult. Therefore, some authors have recommended an indirect operation (carotid artery ligation in the neck) as the procedure of choice. A Consecutive series of eight patients with carotid-ophthalmic aneurysms in presented; a direct operation was performed in seven instances. There was no operative mortality and the morbidity was very low. The direct attack seems to be reliable, and is recommended.", "contents": "Carotid-ophthalmic aneurysms. Carotid-ophthalmic aneurysms have intimate relationships with the ipsilateral optic nerve and other neighboring structures. Direct operation for treatment of these aneurysms has been considered particularly hazardous and difficult. Therefore, some authors have recommended an indirect operation (carotid artery ligation in the neck) as the procedure of choice. A Consecutive series of eight patients with carotid-ophthalmic aneurysms in presented; a direct operation was performed in seven instances. There was no operative mortality and the morbidity was very low. The direct attack seems to be reliable, and is recommended."} {"id": "PMID:1265626", "title": "Arteriovenous malformations of the splenium of the corpus callosum: microsurgical treatment.", "content": "Ten patients with arteriovenous malformations (AVM) involving the splenium of the corpus callosum are presented. All were treated by microsurgical techniques with no mortality and minimal morbidity. The diagnosis and operative technique is described, and these AVMs are compared with those involving the anterior and the middle portions of the corpus callosum.", "contents": "Arteriovenous malformations of the splenium of the corpus callosum: microsurgical treatment. Ten patients with arteriovenous malformations (AVM) involving the splenium of the corpus callosum are presented. All were treated by microsurgical techniques with no mortality and minimal morbidity. The diagnosis and operative technique is described, and these AVMs are compared with those involving the anterior and the middle portions of the corpus callosum."} {"id": "PMID:1265627", "title": "Peripheral nerve injury from implantation of chronic stimulating electrodes for pain control.", "content": "Complications of implantable stimulating electrodes for pain control are becoming recognized. We present two cases of peripheral nerve injury related to placement of peripheral nerve stimulating electrodes and discuss the relevant literature.", "contents": "Peripheral nerve injury from implantation of chronic stimulating electrodes for pain control. Complications of implantable stimulating electrodes for pain control are becoming recognized. We present two cases of peripheral nerve injury related to placement of peripheral nerve stimulating electrodes and discuss the relevant literature."} {"id": "PMID:1265628", "title": "Spontaneous cerebrospinal fluid otorrhea.", "content": "A case of spontaneous cerebrospinal fluid otorrhea with recurrent meningitis is reported. The route of cerebrospinal fluid leak was through the internal auditory meatus. The cerebrospinal fluid otorrhea was stopped by packing the meatus with muscle and Gelfoam.", "contents": "Spontaneous cerebrospinal fluid otorrhea. A case of spontaneous cerebrospinal fluid otorrhea with recurrent meningitis is reported. The route of cerebrospinal fluid leak was through the internal auditory meatus. The cerebrospinal fluid otorrhea was stopped by packing the meatus with muscle and Gelfoam."} {"id": "PMID:1265629", "title": "Computerized tomography correlated with CSF protein concentrations.", "content": "The authors present a case of hydrocephalus complicated by ventriculitis in which it was possible to correlate the numerical printout of sequential computerized tomograms (CT-Scans) with cerebrospinal fluid protein concentrations obtained by direct ventricular puncture. Different protein levels were unambiguously associated with changes in the absorption numbers on the scan but they did not bear a simple linear relationship to one another. The value of the numerical printout in diagnosis and follow-up is discussed.", "contents": "Computerized tomography correlated with CSF protein concentrations. The authors present a case of hydrocephalus complicated by ventriculitis in which it was possible to correlate the numerical printout of sequential computerized tomograms (CT-Scans) with cerebrospinal fluid protein concentrations obtained by direct ventricular puncture. Different protein levels were unambiguously associated with changes in the absorption numbers on the scan but they did not bear a simple linear relationship to one another. The value of the numerical printout in diagnosis and follow-up is discussed."} {"id": "PMID:1265630", "title": "Aqueductal occlusion by midline arteriovenous malformation.", "content": "An adult presented with signs of chronic obstructive hydrocephalus. Angiography showed an arteriovenous malformation in the region of the posterior diencephalon and mesencephalon with venous drainage into the vein of Galen. Pneumoencephalography demonstrated obstruction of the aqueduct. This case affirms the need to consider the presence of an arteriovenous malformation in adults who present with signs of aqueductal stenosis.", "contents": "Aqueductal occlusion by midline arteriovenous malformation. An adult presented with signs of chronic obstructive hydrocephalus. Angiography showed an arteriovenous malformation in the region of the posterior diencephalon and mesencephalon with venous drainage into the vein of Galen. Pneumoencephalography demonstrated obstruction of the aqueduct. This case affirms the need to consider the presence of an arteriovenous malformation in adults who present with signs of aqueductal stenosis."} {"id": "PMID:1265631", "title": "Extracranial meningioma presenting as lytic skull lesion.", "content": "A meningioma that had replaced the outer table of the skull and thinned the inner table but had no intracranial extension appeared as a solitary lytic lesion on routine roentgenograms of the skull. It was removed without complications.", "contents": "Extracranial meningioma presenting as lytic skull lesion. A meningioma that had replaced the outer table of the skull and thinned the inner table but had no intracranial extension appeared as a solitary lytic lesion on routine roentgenograms of the skull. It was removed without complications."} {"id": "PMID:1265632", "title": "Occipital artery-posterior inferior cerebellar artery anastomosis.", "content": "In a 58-year-old man who suffered a stroke and had multiple and extensive extracranial arterial occlusions, an anastomosis was completed between the right occipital artery and the right posterior inferior cerebellar artery. Cerebral angiograms performed two weeks post-operatively showed patent anastomosis and partial improvement of the posterior circulation.", "contents": "Occipital artery-posterior inferior cerebellar artery anastomosis. In a 58-year-old man who suffered a stroke and had multiple and extensive extracranial arterial occlusions, an anastomosis was completed between the right occipital artery and the right posterior inferior cerebellar artery. Cerebral angiograms performed two weeks post-operatively showed patent anastomosis and partial improvement of the posterior circulation."} {"id": "PMID:1265633", "title": "Microsurgical anterior cervical myelotomy.", "content": "Cervical myelotomy utilizing the anterior approach and the operating microscope in a patient with an acute spinal cord injury is described. The procedure overcomes the technical difficulties previously encountered. The ease with which the hemorrhagic gray matter may be separated from the normal gray and surrounding white matter is emphasized.", "contents": "Microsurgical anterior cervical myelotomy. Cervical myelotomy utilizing the anterior approach and the operating microscope in a patient with an acute spinal cord injury is described. The procedure overcomes the technical difficulties previously encountered. The ease with which the hemorrhagic gray matter may be separated from the normal gray and surrounding white matter is emphasized."} {"id": "PMID:1265634", "title": "Experimental cervical myelopathy: autoradiographic studies of spinal cord blood flow patterns.", "content": "The cervical spinal cord was compressed at one (C5) or two (C4,C5) levels in eight awake dogs by advancing screws through the vertebral bodies into the spinal canal until minimal limb weakness occurred. Ischemia of the cervical cord was produced by ligation of vertebral and spinal arteries in four anesthetized dogs, of which two had previously undergone cord compression at two levels. The neurological and histological findings were studied. By means of antipyrine [14C]autoradiography, qualitative changes of blood flow in dogs with compression and/or ischemia of the cervical spinal cord were compared to flow patterns in normal dogs. The authors conclude that the neurological and histological changes produced by spinal cord compression, ischemia and their combination correlate with altered patterns of blood flow within the cervical spinal cord.", "contents": "Experimental cervical myelopathy: autoradiographic studies of spinal cord blood flow patterns. The cervical spinal cord was compressed at one (C5) or two (C4,C5) levels in eight awake dogs by advancing screws through the vertebral bodies into the spinal canal until minimal limb weakness occurred. Ischemia of the cervical cord was produced by ligation of vertebral and spinal arteries in four anesthetized dogs, of which two had previously undergone cord compression at two levels. The neurological and histological findings were studied. By means of antipyrine [14C]autoradiography, qualitative changes of blood flow in dogs with compression and/or ischemia of the cervical spinal cord were compared to flow patterns in normal dogs. The authors conclude that the neurological and histological changes produced by spinal cord compression, ischemia and their combination correlate with altered patterns of blood flow within the cervical spinal cord."} {"id": "PMID:1265635", "title": "Severe epistaxis caused by traumatic aneurysm of cavernous carotid artery.", "content": "A case of cavernous carotid aneurysm presented with unilateral blindness, orbital fracture and recurrent, severe epistaxis of delayed onset. Traumatic origin of aneurysm is confirmed by repeat angiographic studies.", "contents": "Severe epistaxis caused by traumatic aneurysm of cavernous carotid artery. A case of cavernous carotid aneurysm presented with unilateral blindness, orbital fracture and recurrent, severe epistaxis of delayed onset. Traumatic origin of aneurysm is confirmed by repeat angiographic studies."} {"id": "PMID:1265637", "title": "Arachnoid cysts of the middle cranial fossa.", "content": "Arachnoid cysts of the middle cranial fossa may present clinically in several different ways. They may remain asymptomatic throughout life, or may cause only local bulging of the skull, with or without exophthalmos. Expansion of the cyst may occur through a ball-valve mechanism of its membrane in communication with the general subarachnoid space leading to increased intracranial pressure with or without localizing neurological deficits. Finally, such cysts are associated with increased vulnerability to the effects of head injury, resulting in hemorrhage either into the cyst or external to the cyst to form a subdural hematoma. Recognition of these various manifestations is essential to proper treatment.", "contents": "Arachnoid cysts of the middle cranial fossa. Arachnoid cysts of the middle cranial fossa may present clinically in several different ways. They may remain asymptomatic throughout life, or may cause only local bulging of the skull, with or without exophthalmos. Expansion of the cyst may occur through a ball-valve mechanism of its membrane in communication with the general subarachnoid space leading to increased intracranial pressure with or without localizing neurological deficits. Finally, such cysts are associated with increased vulnerability to the effects of head injury, resulting in hemorrhage either into the cyst or external to the cyst to form a subdural hematoma. Recognition of these various manifestations is essential to proper treatment."} {"id": "PMID:1265638", "title": "Pellet-gun brain wound complicated by Clostridium Perfringens meningitis.", "content": "A ten-year-old male was hospitalized for a pellet-gun wound to the brain. He developed Clostridial meningitis within eighteen hours in spite of radical debridement and prophylactic antibiotics. However, successful recovery was obtained with high levels of penicillin and chloromycetin antibiotic therapy.", "contents": "Pellet-gun brain wound complicated by Clostridium Perfringens meningitis. A ten-year-old male was hospitalized for a pellet-gun wound to the brain. He developed Clostridial meningitis within eighteen hours in spite of radical debridement and prophylactic antibiotics. However, successful recovery was obtained with high levels of penicillin and chloromycetin antibiotic therapy."} {"id": "PMID:1265640", "title": "Neurogenic intermittent claudication and stenosis of the lumbar spinal canal.", "content": "Neurogenic intermittent claudication is briefly reviewed and correlated with twenty consecutive cases of lumbar spinal canal stenosis. Irreversible damage may occur if surgical decompression is unduly delayed. A unilateral decompression may be sufficient in carefully selected cases.", "contents": "Neurogenic intermittent claudication and stenosis of the lumbar spinal canal. Neurogenic intermittent claudication is briefly reviewed and correlated with twenty consecutive cases of lumbar spinal canal stenosis. Irreversible damage may occur if surgical decompression is unduly delayed. A unilateral decompression may be sufficient in carefully selected cases."} {"id": "PMID:1265641", "title": "A practical method for measuring hydrodynamics of cerebrospinal fluid.", "content": "A method for measuring the formation and absorption rates of cerebrospinal fluid is described which can be carried out relatively rapidly and with a minimum of expensive apparatus. It has been found particularly useful in the evaluation of patients with hydrocephalus.", "contents": "A practical method for measuring hydrodynamics of cerebrospinal fluid. A method for measuring the formation and absorption rates of cerebrospinal fluid is described which can be carried out relatively rapidly and with a minimum of expensive apparatus. It has been found particularly useful in the evaluation of patients with hydrocephalus."} {"id": "PMID:1265643", "title": "Surgical and angiographic localization of spinal arteriovenous malformations.", "content": "Three cases of spinal arteriovenous malformation are reported which illustrate that localization of intra- and extramedullary components are not always adequately assessed by spinal angiography alone. One large malformation, primarily dorsal to the spinal cord, was not seen on angiography. A second lesion thought to be intramedullary and unresectable as judged by angiography was found at surgery to be primarily dorsolateral and was resected. The third malformation was thought to be extramedullary on angiography, yet had a major intramedullary component at surgery and was not resected. We conclude that surgical exploration of all spinal arteriovenous malformations should be performed despite the angiographic appearance.", "contents": "Surgical and angiographic localization of spinal arteriovenous malformations. Three cases of spinal arteriovenous malformation are reported which illustrate that localization of intra- and extramedullary components are not always adequately assessed by spinal angiography alone. One large malformation, primarily dorsal to the spinal cord, was not seen on angiography. A second lesion thought to be intramedullary and unresectable as judged by angiography was found at surgery to be primarily dorsolateral and was resected. The third malformation was thought to be extramedullary on angiography, yet had a major intramedullary component at surgery and was not resected. We conclude that surgical exploration of all spinal arteriovenous malformations should be performed despite the angiographic appearance."} {"id": "PMID:1265645", "title": "Convulsions subarachnoid haemorrhage and death following myelography with meglumine iothalamate 280.", "content": "A case is presented of convulsions, subarachnoid haemorrhage and death following the use of meglumine iothalamate 280 for myelography. The patient was suffering from sciatica but had no pre-existing symptoms of other neurological disease. This case dramatically illustrates the dangers inherent in the use of meglumine iothalamate 280 for myelography.", "contents": "Convulsions subarachnoid haemorrhage and death following myelography with meglumine iothalamate 280. A case is presented of convulsions, subarachnoid haemorrhage and death following the use of meglumine iothalamate 280 for myelography. The patient was suffering from sciatica but had no pre-existing symptoms of other neurological disease. This case dramatically illustrates the dangers inherent in the use of meglumine iothalamate 280 for myelography."} {"id": "PMID:1265646", "title": "Epidural venography in the diagnosis of lumbar disc disease.", "content": "Epidural venography is a simple and effective technic in the diagnosis of herniated intervertebral discs. The procedure may be performed in the outpatient department using percutaneous transfemoral catheterization. Our experience in 87 cases suggests that epidural venography is superior to Pantopaque myelography at the L5-S1 level, comparable to, and in some cases superior, at the L4-L5 level. The epidural venogram was abnormal in 33 cases. The findings were confirmed at operation in 25 of these. The remaining eight patients are being followed or are awaiting surgical treatment. Twenty of the 25 cases had had normal Pantopaque myelograms. Fifty-four of the 87 cases were considered to be normal.", "contents": "Epidural venography in the diagnosis of lumbar disc disease. Epidural venography is a simple and effective technic in the diagnosis of herniated intervertebral discs. The procedure may be performed in the outpatient department using percutaneous transfemoral catheterization. Our experience in 87 cases suggests that epidural venography is superior to Pantopaque myelography at the L5-S1 level, comparable to, and in some cases superior, at the L4-L5 level. The epidural venogram was abnormal in 33 cases. The findings were confirmed at operation in 25 of these. The remaining eight patients are being followed or are awaiting surgical treatment. Twenty of the 25 cases had had normal Pantopaque myelograms. Fifty-four of the 87 cases were considered to be normal."} {"id": "PMID:1265647", "title": "Acute spinal epidural hematoma secondary to aspirin-induced prolonged bleeding.", "content": "A case of acute and spontaneous spinal epidural hemorrhage is described in which there was no history or evidence of trauma, conventional anticoagulant therapy, hemophilia or vascular anomalies. A recent history of excessive ingestion of an aspirin-containing medication was obtained and the clinical and laboratory picture of an aspirin-induced bleeding disorder was documented. We have discussed the mechanism and hematological considerations of the syndrome of aspirin induced bleeding.", "contents": "Acute spinal epidural hematoma secondary to aspirin-induced prolonged bleeding. A case of acute and spontaneous spinal epidural hemorrhage is described in which there was no history or evidence of trauma, conventional anticoagulant therapy, hemophilia or vascular anomalies. A recent history of excessive ingestion of an aspirin-containing medication was obtained and the clinical and laboratory picture of an aspirin-induced bleeding disorder was documented. We have discussed the mechanism and hematological considerations of the syndrome of aspirin induced bleeding."} {"id": "PMID:1265648", "title": "Aneurysm rupture during angiography: does acute vasospasm occur?", "content": "Thirty-two cases of rupture of an aneurysm during angiography were reviewed to determine whether there is an immediate, acute phase of intracranial arterial spasm in human beings. Unfortunately, in the 11 instances of major extravasation into the adjacent subarachnoid spaces (the cases most likely to demonstrate arterial spasm), the arteries either were not filled or were obscured by the escaping contrast medium. In 13 patients who demonstrated arterial spasm, the vasospasm definitely (5), probably (6), or possibly (2) was related to a prior episode of bleeding. There was no evidence of arterial spasm in the other eight cases. Therefore there is no definite proof from the present investigation that an acute phase of intracranial arterial spasm occurs following rupture of an aneurysm.", "contents": "Aneurysm rupture during angiography: does acute vasospasm occur? Thirty-two cases of rupture of an aneurysm during angiography were reviewed to determine whether there is an immediate, acute phase of intracranial arterial spasm in human beings. Unfortunately, in the 11 instances of major extravasation into the adjacent subarachnoid spaces (the cases most likely to demonstrate arterial spasm), the arteries either were not filled or were obscured by the escaping contrast medium. In 13 patients who demonstrated arterial spasm, the vasospasm definitely (5), probably (6), or possibly (2) was related to a prior episode of bleeding. There was no evidence of arterial spasm in the other eight cases. Therefore there is no definite proof from the present investigation that an acute phase of intracranial arterial spasm occurs following rupture of an aneurysm."} {"id": "PMID:1265649", "title": "Cerebral tuberculoma localized by EMI scan.", "content": "A case of isolated supratentorial tuberculoma is described. The patient had a left facial palsy, left hemiplegia, and left proprioceptive and stereognostic deficits with negative studies until the lesion was delineated with computerized axial tomography (EMI scan). The characteristics EMI scan is helpful in delineating the nature and precise location of the lesion prior to surgery.", "contents": "Cerebral tuberculoma localized by EMI scan. A case of isolated supratentorial tuberculoma is described. The patient had a left facial palsy, left hemiplegia, and left proprioceptive and stereognostic deficits with negative studies until the lesion was delineated with computerized axial tomography (EMI scan). The characteristics EMI scan is helpful in delineating the nature and precise location of the lesion prior to surgery."} {"id": "PMID:1265650", "title": "Monitoring and control of intracranial pressure in non-traumatic encephalopathies.", "content": "Fifteen patients with non-traumatic encephalopathies underwent continuous monitoring of intracranial pressure. These included 11 children with Reye's syndrome, two with viral encephalitis, one with mushroom poisoning, and one with hypoxia from drowning. Elevated intracranial pressure was treated with decadron, hyperventilation, hyperosmolar agents and in some cases hypothermia and barbiturates. The results are discussed.", "contents": "Monitoring and control of intracranial pressure in non-traumatic encephalopathies. Fifteen patients with non-traumatic encephalopathies underwent continuous monitoring of intracranial pressure. These included 11 children with Reye's syndrome, two with viral encephalitis, one with mushroom poisoning, and one with hypoxia from drowning. Elevated intracranial pressure was treated with decadron, hyperventilation, hyperosmolar agents and in some cases hypothermia and barbiturates. The results are discussed."} {"id": "PMID:1265651", "title": "An apparatus for quantitating experimental spinal cord trauma.", "content": "An apparatus is described for producing experimental contusion of the spinal cord and simultaneously monitoring the degree of trauma: velocity of spinal cord deformation, impulse and energy. This is accomplished by modifying an existing trauma apparatus by the addition of a displacement transducer, an induction coil triggering device and oscilloscope. With variability in the mechanics of the trauma apparatus and biological variations in each animal (i.e. differences in the visco-elastic properties of the spinal cord, etc.) and in different kinds of animals, this apparatus will more accurately quantitate the trauma delivered to each spinal cord and, thereby, form a better basis for correlation of amount of injury, degree of neurological dysfunction and efficacy of various methods of treatment.", "contents": "An apparatus for quantitating experimental spinal cord trauma. An apparatus is described for producing experimental contusion of the spinal cord and simultaneously monitoring the degree of trauma: velocity of spinal cord deformation, impulse and energy. This is accomplished by modifying an existing trauma apparatus by the addition of a displacement transducer, an induction coil triggering device and oscilloscope. With variability in the mechanics of the trauma apparatus and biological variations in each animal (i.e. differences in the visco-elastic properties of the spinal cord, etc.) and in different kinds of animals, this apparatus will more accurately quantitate the trauma delivered to each spinal cord and, thereby, form a better basis for correlation of amount of injury, degree of neurological dysfunction and efficacy of various methods of treatment."} {"id": "PMID:1265654", "title": "The use of expanded microporous polytetrafluoroethylene for limb salvage: a preliminary report.", "content": "Initial laboratory and clinical evaluations of a new prosthetic material, expanded microporous polytetrafluoroethylene (PTFE), for small vessel replacement is promising and encourages further clinical trial. Frequently the autogenous saphenous vein is not available for bypass procedures, and alternative arterial substitutes have not proved reliable for replacement of small vessels. In this study, 15 patients with impending loss of limb and no available saphenous vein underwent revascularization of the lower extremity with expanded microporous PTFE grafts. Thirteen of 15 patients now demonstrate viable extremities with a resulting over-all early patency and limb salvage rate of 87 percent for this series. Follow-up ranges from one to 8 months. Seven patients had diabetes mellitus and eight had atherosclerotic heart disease. Nine grafts crossed the knee joint. In all patients arterial runoff was poor. Six patients had previous femoropopliteal bypasses, five with autogenous veins and one with Dacron velour. Two patients had multiple previous operations that failed, first with autogenous vein and later with fabric grafts. The current limb salvage and patency rate of 87 percent in high-risk patients suggests that expanded PTFE may be the prosthesis of choice when an autogenous vein is not available and possibly an equally good substitute when the venous autograft is available.", "contents": "The use of expanded microporous polytetrafluoroethylene for limb salvage: a preliminary report. Initial laboratory and clinical evaluations of a new prosthetic material, expanded microporous polytetrafluoroethylene (PTFE), for small vessel replacement is promising and encourages further clinical trial. Frequently the autogenous saphenous vein is not available for bypass procedures, and alternative arterial substitutes have not proved reliable for replacement of small vessels. In this study, 15 patients with impending loss of limb and no available saphenous vein underwent revascularization of the lower extremity with expanded microporous PTFE grafts. Thirteen of 15 patients now demonstrate viable extremities with a resulting over-all early patency and limb salvage rate of 87 percent for this series. Follow-up ranges from one to 8 months. Seven patients had diabetes mellitus and eight had atherosclerotic heart disease. Nine grafts crossed the knee joint. In all patients arterial runoff was poor. Six patients had previous femoropopliteal bypasses, five with autogenous veins and one with Dacron velour. Two patients had multiple previous operations that failed, first with autogenous vein and later with fabric grafts. The current limb salvage and patency rate of 87 percent in high-risk patients suggests that expanded PTFE may be the prosthesis of choice when an autogenous vein is not available and possibly an equally good substitute when the venous autograft is available."} {"id": "PMID:1265657", "title": "A modified method for the repair of esophageal atresia with tracheoesophageal fistula.", "content": "Forty patients with esophageal atresia with tracheoesophageal fistula were operated upon during a period of 2 years, 39 of them with the end-to-side anastomosis technique. According to Waterston's classification, the survival rate was 91 percent for Group A (11 patients), 60 percent for Group B (15 patients), and 14 percent for Group C (14 patients). A prospective study carried out with the first 30 patients showed that the partial removal of the mucosa of the lower esophagus, just distal to its junction with the trachea, reduced significantly the incidence of recanalization of the tracheoesophageal fistula.", "contents": "A modified method for the repair of esophageal atresia with tracheoesophageal fistula. Forty patients with esophageal atresia with tracheoesophageal fistula were operated upon during a period of 2 years, 39 of them with the end-to-side anastomosis technique. According to Waterston's classification, the survival rate was 91 percent for Group A (11 patients), 60 percent for Group B (15 patients), and 14 percent for Group C (14 patients). A prospective study carried out with the first 30 patients showed that the partial removal of the mucosa of the lower esophagus, just distal to its junction with the trachea, reduced significantly the incidence of recanalization of the tracheoesophageal fistula."} {"id": "PMID:1265658", "title": "Tracheomalacia in association with congenital tracheoesophageal fistula.", "content": "Tracheomalacia is an important cause of morbidity and death following correction of congenital tracheoesophageal fistula and is a well defined syndrome which requires recognition and appropriate treatment. The symptoms and signs allow division into mild, moderate, and severe groups. When the clinical features suggest the presence of tracheomalacia, endoscopy should be carried out in order to confirm the diagnosis and document the severity. Mild and moderate cases can be managed conservatively; efficient and regular physiotherapy is the mainstay of treatment. Severe cases warrant consideration for the operation of tracheopexy which may be lifesaving and will certainly reduce the period of hospitalization and will simplify management.", "contents": "Tracheomalacia in association with congenital tracheoesophageal fistula. Tracheomalacia is an important cause of morbidity and death following correction of congenital tracheoesophageal fistula and is a well defined syndrome which requires recognition and appropriate treatment. The symptoms and signs allow division into mild, moderate, and severe groups. When the clinical features suggest the presence of tracheomalacia, endoscopy should be carried out in order to confirm the diagnosis and document the severity. Mild and moderate cases can be managed conservatively; efficient and regular physiotherapy is the mainstay of treatment. Severe cases warrant consideration for the operation of tracheopexy which may be lifesaving and will certainly reduce the period of hospitalization and will simplify management."} {"id": "PMID:1265653", "title": "Lady Luck.", "content": "When a patient with no distance complaints is unable to read with comfort, a shift in the cylinder axes should be among the first things considered. A simple technique for measuring the axes is described, interpretation of the measurements is discussed, and various therapeutic approaches are suggested.", "contents": "Lady Luck. When a patient with no distance complaints is unable to read with comfort, a shift in the cylinder axes should be among the first things considered. A simple technique for measuring the axes is described, interpretation of the measurements is discussed, and various therapeutic approaches are suggested."} {"id": "PMID:1265659", "title": "Influence of a synthetic prostaglandin analog on pancreatic secretion.", "content": "Effects of a synthetic prostaglandin analog-16--16-dimethyl prostaglandin E2, methyl ester (16-diMe-PGE2)--on pancreatic secretion were evaluated in seven dogs with chronic duodenal fistulas. Graded doses of 16-diMe-PGE2 were administered intravenously (0.1, 0.3, 0.5, and 1.0 mug per kilogram, intraduodenally, or intragastrically (15, 30, 50, 100 mug per kilogram) with the pancreas in the resting state or in response to (1) secretin and (2) secretin with cholecystokinin-pancreozymin. Profound and prolonged inhibition of volume and bicarbonate concentration of secretion occurred in the resting and stimulated gland. ED50 was 0.31 mug per kilogram intravenously (1/75 the ED50 for PGE1) and 25 mug per kilogram intraduodenally. As with PGE1, stimulation of enzymes occurred, even with doses that were subthreshold for inhibition of volume and HCO3. Like PGE1, 16-diMe-PGE2 has a dual action on the intact canine pancreas (stimulation of enzymes and inhibition of volume and electrolytes), but is much more potent, has a prolonged action, and is active intraduodenally and intragastrically. Nonsteroid inhibitors of endogenous prostaglandin synthesis did not alter these effects.", "contents": "Influence of a synthetic prostaglandin analog on pancreatic secretion. Effects of a synthetic prostaglandin analog-16--16-dimethyl prostaglandin E2, methyl ester (16-diMe-PGE2)--on pancreatic secretion were evaluated in seven dogs with chronic duodenal fistulas. Graded doses of 16-diMe-PGE2 were administered intravenously (0.1, 0.3, 0.5, and 1.0 mug per kilogram, intraduodenally, or intragastrically (15, 30, 50, 100 mug per kilogram) with the pancreas in the resting state or in response to (1) secretin and (2) secretin with cholecystokinin-pancreozymin. Profound and prolonged inhibition of volume and bicarbonate concentration of secretion occurred in the resting and stimulated gland. ED50 was 0.31 mug per kilogram intravenously (1/75 the ED50 for PGE1) and 25 mug per kilogram intraduodenally. As with PGE1, stimulation of enzymes occurred, even with doses that were subthreshold for inhibition of volume and HCO3. Like PGE1, 16-diMe-PGE2 has a dual action on the intact canine pancreas (stimulation of enzymes and inhibition of volume and electrolytes), but is much more potent, has a prolonged action, and is active intraduodenally and intragastrically. Nonsteroid inhibitors of endogenous prostaglandin synthesis did not alter these effects."} {"id": "PMID:1265660", "title": "Vascular compression of the duodenum: Presentation of ten cases and review of the literature.", "content": "Ten cases of vascular compression of the duodenum are presented, and 125 cases in the literature since 1962 are reviewed. More common in women than in men, the lesion may result from supine immobilization, wearing body cast, or a rapid weight loss. In about one third of the patients, no predisposing factor can be found. Diagnosis is best made by cinefluoroscopy. Although conservative measures will provide relief in a few patients, most will require surgery. Section of the suspensory muscle and relocation of the duodenojejunal junction will relieve the symptoms in many patients. Duodenojejunostomy will be required in some others. Complete relief can be expected in all but a very few patients. Those who have developed neurotic eating habits from years of discomfort may not show immediate improvement. Untreated vascular compression of the duodenum may be chronic or may become acute with fatal results.", "contents": "Vascular compression of the duodenum: Presentation of ten cases and review of the literature. Ten cases of vascular compression of the duodenum are presented, and 125 cases in the literature since 1962 are reviewed. More common in women than in men, the lesion may result from supine immobilization, wearing body cast, or a rapid weight loss. In about one third of the patients, no predisposing factor can be found. Diagnosis is best made by cinefluoroscopy. Although conservative measures will provide relief in a few patients, most will require surgery. Section of the suspensory muscle and relocation of the duodenojejunal junction will relieve the symptoms in many patients. Duodenojejunostomy will be required in some others. Complete relief can be expected in all but a very few patients. Those who have developed neurotic eating habits from years of discomfort may not show immediate improvement. Untreated vascular compression of the duodenum may be chronic or may become acute with fatal results."} {"id": "PMID:1265661", "title": "Effect of dehydration and cardiac tamponade on superior mesenteric artery flow: role of vasoactive substances.", "content": "The role of serotonin, catecholamines, and angiotensin in the pathogenesis of mesenteric low flow states was investigated in anesthetized dogs by measurement of blood flows with electromagnetic flow meters. During dehydration or cardiac tamponade, a disproportionate decrease in superior mesenteric artery flow was demonstrated, compared with aortic flow, but renal artery flow was relatively better maintained. Depletion of serotonin and catecholamines by pretreatment with reserpine or blocking serotonin's action with methysergide did not alter the disproportionate reduction in mesenteric flow. Disproportionate superior mesenteric artery flow during dehydration and tamponade was associated with increased levels of circulating angiotensin and virtually was abolished by bilateral nephrectomy, by inhibition of enzymatic conversion of angiotensin I to II by Bothrops nonapeptide, and by competitive inhibition of angiotensin II with 1-sar, 8-ala angiotensin II. Exogenous angiotensin administered intravenously to dogs not protected by drug treatment disproportionately decreased superior mesenteric artery flow with less effect on renal artery flow. These results are compatible with the hypothesis that increased circulating levels of angiotensin during dehydration and tamponade contribute to the disproportionate reduction in superior mesenteric artery flow in the anesthetized dog.", "contents": "Effect of dehydration and cardiac tamponade on superior mesenteric artery flow: role of vasoactive substances. The role of serotonin, catecholamines, and angiotensin in the pathogenesis of mesenteric low flow states was investigated in anesthetized dogs by measurement of blood flows with electromagnetic flow meters. During dehydration or cardiac tamponade, a disproportionate decrease in superior mesenteric artery flow was demonstrated, compared with aortic flow, but renal artery flow was relatively better maintained. Depletion of serotonin and catecholamines by pretreatment with reserpine or blocking serotonin's action with methysergide did not alter the disproportionate reduction in mesenteric flow. Disproportionate superior mesenteric artery flow during dehydration and tamponade was associated with increased levels of circulating angiotensin and virtually was abolished by bilateral nephrectomy, by inhibition of enzymatic conversion of angiotensin I to II by Bothrops nonapeptide, and by competitive inhibition of angiotensin II with 1-sar, 8-ala angiotensin II. Exogenous angiotensin administered intravenously to dogs not protected by drug treatment disproportionately decreased superior mesenteric artery flow with less effect on renal artery flow. These results are compatible with the hypothesis that increased circulating levels of angiotensin during dehydration and tamponade contribute to the disproportionate reduction in superior mesenteric artery flow in the anesthetized dog."} {"id": "PMID:1265662", "title": "Thoracic problems associated with hydatid cyst of the dome of the liver.", "content": "Twenty patients with hydatid cyst of the dome of the liver are presented. In ten there were significant associated intrathoracic complications including pleural effusion, pleural empyema, erosion through the diaphragm into lung, various degrees of pneumonitis or pulmonary abscess, or severe destruction of both diaphragm and right lower pulmonary lobe. Bronchobiliary fistula was demonstrated at operation in five patients. Four patients had obstructive jaundice due to intrabiliary rupture of a liver hydatid. In 19 patients the cysts in the right lobe of the liver were evacuated through a right thoracotomy and incision of the diaphragm. In four of these, additional pulmonary resection was carried out. In one patient with left pleural empyema, tube drainage followed by rib resection was instituted. Two patients had common duct drainage for relief of obstructive jaundice. In 13 patients the ectocyst cavity was drained; in seven it was filled with saline and closed. One patient required evacuation and open packing of the right upper quadrant and lower right hemithorax. Thoracotomy is mandatory in patients with hydatid cyst of the dome of the liver for easier approach to the cyst and for management of coexisting intrathoracic complications.", "contents": "Thoracic problems associated with hydatid cyst of the dome of the liver. Twenty patients with hydatid cyst of the dome of the liver are presented. In ten there were significant associated intrathoracic complications including pleural effusion, pleural empyema, erosion through the diaphragm into lung, various degrees of pneumonitis or pulmonary abscess, or severe destruction of both diaphragm and right lower pulmonary lobe. Bronchobiliary fistula was demonstrated at operation in five patients. Four patients had obstructive jaundice due to intrabiliary rupture of a liver hydatid. In 19 patients the cysts in the right lobe of the liver were evacuated through a right thoracotomy and incision of the diaphragm. In four of these, additional pulmonary resection was carried out. In one patient with left pleural empyema, tube drainage followed by rib resection was instituted. Two patients had common duct drainage for relief of obstructive jaundice. In 13 patients the ectocyst cavity was drained; in seven it was filled with saline and closed. One patient required evacuation and open packing of the right upper quadrant and lower right hemithorax. Thoracotomy is mandatory in patients with hydatid cyst of the dome of the liver for easier approach to the cyst and for management of coexisting intrathoracic complications."} {"id": "PMID:1265663", "title": "Renal hemodynamic response to furosemide in septic and injured patients.", "content": "Furosemide frequently is advocated as a prophylaxis against renal failure in septic and injured patients; this effect is thought to be secondary to an increase in renal blood flow. This postulate was tested within 72 hours of admission in 22 previously healthy patients with acute pancreatitis (two), massive trauma (ten), or severe sepsis (ten). Renal clearances of inulin (GFR), para-amino hippurate (ERPF), sodium (CNA), osmoles (COsm), and free water (CH2O) were measured in milliliters per minute before and after the intravenous infusion of furosemide (0.5 mg. per kilogram of body weight). Renal vein PAH levels (EPAH) in eight patients were used to calculate true renal plasma flow (TRPF), true renal blood flow (TRBF), and renal vascular resistance (RVR). Furosemide caused a significant increase in urine volume, CNa, and COsm; there were no significant changes in GFR, ERPF, RVR, TRBF, and EPAH. These findings also were observed when the patients were subgrouped according to elevated, normal, or low renal plasma flow and elevated renal vascular resistance. No significant changes were seen in EPAH, thus making a redistribution of renal blood flow unlikely. These studies indicate that furosemide has only a diuretic effect and no hemodynamic effect in the kidney; it has the potential of seriously reducing the circulatory volume and causing renal failure in critical patients.", "contents": "Renal hemodynamic response to furosemide in septic and injured patients. Furosemide frequently is advocated as a prophylaxis against renal failure in septic and injured patients; this effect is thought to be secondary to an increase in renal blood flow. This postulate was tested within 72 hours of admission in 22 previously healthy patients with acute pancreatitis (two), massive trauma (ten), or severe sepsis (ten). Renal clearances of inulin (GFR), para-amino hippurate (ERPF), sodium (CNA), osmoles (COsm), and free water (CH2O) were measured in milliliters per minute before and after the intravenous infusion of furosemide (0.5 mg. per kilogram of body weight). Renal vein PAH levels (EPAH) in eight patients were used to calculate true renal plasma flow (TRPF), true renal blood flow (TRBF), and renal vascular resistance (RVR). Furosemide caused a significant increase in urine volume, CNa, and COsm; there were no significant changes in GFR, ERPF, RVR, TRBF, and EPAH. These findings also were observed when the patients were subgrouped according to elevated, normal, or low renal plasma flow and elevated renal vascular resistance. No significant changes were seen in EPAH, thus making a redistribution of renal blood flow unlikely. These studies indicate that furosemide has only a diuretic effect and no hemodynamic effect in the kidney; it has the potential of seriously reducing the circulatory volume and causing renal failure in critical patients."} {"id": "PMID:1265664", "title": "An experimental study of gastric healing following scalpel and diathermy incisions.", "content": "To date there has been no reliable information available which compares gastric healing following incisions made by scalpel and diathermy. Standard incisions were made in rat stomachs, half with a scalpel and half with diathermy, following which they were closed in a standard fashion. Healing was assessed at intervals by bursting and tensile strength measurements, angiography, and histology. All incisions were healed by the tenth day. The only significant difference discovered was that histologically there was a definite lag in healing up to the fifth day in those incisions made by diathermy. It is suspected that this is due to mucosa having been dragged into the wound edges by adherence to the diathermy knife.", "contents": "An experimental study of gastric healing following scalpel and diathermy incisions. To date there has been no reliable information available which compares gastric healing following incisions made by scalpel and diathermy. Standard incisions were made in rat stomachs, half with a scalpel and half with diathermy, following which they were closed in a standard fashion. Healing was assessed at intervals by bursting and tensile strength measurements, angiography, and histology. All incisions were healed by the tenth day. The only significant difference discovered was that histologically there was a definite lag in healing up to the fifth day in those incisions made by diathermy. It is suspected that this is due to mucosa having been dragged into the wound edges by adherence to the diathermy knife."} {"id": "PMID:1265665", "title": "Gastric mucosal contraction.", "content": "In this study the role that contraction plays in the healing of gastric wounds is explored experimentally. Superficial gastric mucosal defects made in the columnar part of rat stomachs were found to close rapidly, compared to defects carried down into the muscle layer. The collagen was packed tightly at the edges of the defects and no other factors appeared to have played a part in the closure. It is surmised that the decrease in size of the defect is due to fibroblastic activity causing contraction. It would seem likely that the myofibroblast, as described by other investigators, would be the unique cell causing this action. Further studies are required to confirm or refute this hypothesis.", "contents": "Gastric mucosal contraction. In this study the role that contraction plays in the healing of gastric wounds is explored experimentally. Superficial gastric mucosal defects made in the columnar part of rat stomachs were found to close rapidly, compared to defects carried down into the muscle layer. The collagen was packed tightly at the edges of the defects and no other factors appeared to have played a part in the closure. It is surmised that the decrease in size of the defect is due to fibroblastic activity causing contraction. It would seem likely that the myofibroblast, as described by other investigators, would be the unique cell causing this action. Further studies are required to confirm or refute this hypothesis."} {"id": "PMID:1265666", "title": "Evidence for a humoral factor in unilaterally nephrectomized dogs stimulating renal growth in isolated canine kidneys.", "content": "Totally isolated canine kidneys were perfused at 37 degrees C. for 240 minutes with whole blood from dogs that had undergone a sham operation or a unilateral nephrectomy 24 hours previously. Renal blood flow, glomerular filtration rate, serum sodium, and serum osmolality were not significantly different in the experimental and control preparations. Nucleic acid synthesis as measured by 3H-adenine incorporation was 75 percent higher (p less than 0.01) in the kidneys perfused with blood from the neprectomized dogs. This result supports the theory that a blood-borne factor stimulates nucleic acid synthesis and initiates compensatory renal growth.", "contents": "Evidence for a humoral factor in unilaterally nephrectomized dogs stimulating renal growth in isolated canine kidneys. Totally isolated canine kidneys were perfused at 37 degrees C. for 240 minutes with whole blood from dogs that had undergone a sham operation or a unilateral nephrectomy 24 hours previously. Renal blood flow, glomerular filtration rate, serum sodium, and serum osmolality were not significantly different in the experimental and control preparations. Nucleic acid synthesis as measured by 3H-adenine incorporation was 75 percent higher (p less than 0.01) in the kidneys perfused with blood from the neprectomized dogs. This result supports the theory that a blood-borne factor stimulates nucleic acid synthesis and initiates compensatory renal growth."} {"id": "PMID:1265667", "title": "Limitations of the Doppler cerebrovascular examination in hemispheric cerebral ischemia.", "content": "The results of a directional Doppler ultrasound cerebrovascular examination were compared with arteriographic findings in 56 patients with resolved hemispheric strokes or transient ischemic attacks. Aortic arch arteriography revealed appropriate internal carotid artery lesions which were amenable to endarterectomy in 36 patients (64 percent). Of this group, abnormal Doppler findings were present in only 11 patients (31 percent). The definitive clinical applications of the Doppler cerebrovascular examination are limited to those settings in which demonstration of altered hemodynamics is decisive. In view of the apparent preponderance of embolic rather than hemodynamic mechanisms in the pathogenesis of focal cerebral ischemia, the Doppler examinations has only an adjunctive role in the evaluation of most patients with hemispheric symptoms of cerebrovascular occlusive disease. In such patients, preselection of candidates for diagnostic arteriography is an inappropriate application of the Doppler cerebrovascular examination.", "contents": "Limitations of the Doppler cerebrovascular examination in hemispheric cerebral ischemia. The results of a directional Doppler ultrasound cerebrovascular examination were compared with arteriographic findings in 56 patients with resolved hemispheric strokes or transient ischemic attacks. Aortic arch arteriography revealed appropriate internal carotid artery lesions which were amenable to endarterectomy in 36 patients (64 percent). Of this group, abnormal Doppler findings were present in only 11 patients (31 percent). The definitive clinical applications of the Doppler cerebrovascular examination are limited to those settings in which demonstration of altered hemodynamics is decisive. In view of the apparent preponderance of embolic rather than hemodynamic mechanisms in the pathogenesis of focal cerebral ischemia, the Doppler examinations has only an adjunctive role in the evaluation of most patients with hemispheric symptoms of cerebrovascular occlusive disease. In such patients, preselection of candidates for diagnostic arteriography is an inappropriate application of the Doppler cerebrovascular examination."} {"id": "PMID:1265668", "title": "Scanning electron microscopic observations of the common carotid artery of the rat. III. Heparin effect on platelets.", "content": "After administration of high systemic doses of heparin verified by assay, common carotid arteries in the rat were divided and sutured. Scanning electron microscope observations of endothelial surfaces showed a decrease in platelet adhesion, as well as a reduction in the adherence of other circulatory blood elements when compared to controls. This is the first report indicating the in vivo effect of high dose systemic heparin on platelets.", "contents": "Scanning electron microscopic observations of the common carotid artery of the rat. III. Heparin effect on platelets. After administration of high systemic doses of heparin verified by assay, common carotid arteries in the rat were divided and sutured. Scanning electron microscope observations of endothelial surfaces showed a decrease in platelet adhesion, as well as a reduction in the adherence of other circulatory blood elements when compared to controls. This is the first report indicating the in vivo effect of high dose systemic heparin on platelets."} {"id": "PMID:1265669", "title": "New electric drill biopsy apparatus for breast tumors.", "content": "A simple method of biopsy for breast tumors by means of a new electric drill is described. Biopsy with this apparatus is performed safely and accurately, and it is possible to obtain a part of suspect tumor large enough to allow histological diagnosis. This biopsy apparatus could contribute to early detection of breast carcinoma and the results of surgical treatment would be improved.", "contents": "New electric drill biopsy apparatus for breast tumors. A simple method of biopsy for breast tumors by means of a new electric drill is described. Biopsy with this apparatus is performed safely and accurately, and it is possible to obtain a part of suspect tumor large enough to allow histological diagnosis. This biopsy apparatus could contribute to early detection of breast carcinoma and the results of surgical treatment would be improved."} {"id": "PMID:1265670", "title": "Celiac artery aneurysmectomy: case report with review of the literature.", "content": "A case of celiac trunk aneurysm treated by excision and direct reanastomosis with restoration of arterial continuity, and a description of a new technique for selective visualization of the celiac artery are reported. A review of the literature with tabulation of all surgically treated cases is included. Significance of hepatic artery flow restoration is emphasized.", "contents": "Celiac artery aneurysmectomy: case report with review of the literature. A case of celiac trunk aneurysm treated by excision and direct reanastomosis with restoration of arterial continuity, and a description of a new technique for selective visualization of the celiac artery are reported. A review of the literature with tabulation of all surgically treated cases is included. Significance of hepatic artery flow restoration is emphasized."} {"id": "PMID:1265671", "title": "Vascular insufficiency secondary to ergotism.", "content": "A case of ergot-induced peripheral vascular insufficiency mimicking atherosclerosis is presented and the clinical symptoms with vascular laboratory evaluation and roentgenographic findings are discussed in detail. A review of the literature of the vascular complications of ergot alkaloids is presented. After considering the various therapeutic modalities employed, a conservative, but hopefully more rational, treatment for these lesions is recommended. Although uncommon, this problem always must be considered in the differential diagnosis of the young patient, especially female, who presents with visceral or peripheral arterial insufficiency.", "contents": "Vascular insufficiency secondary to ergotism. A case of ergot-induced peripheral vascular insufficiency mimicking atherosclerosis is presented and the clinical symptoms with vascular laboratory evaluation and roentgenographic findings are discussed in detail. A review of the literature of the vascular complications of ergot alkaloids is presented. After considering the various therapeutic modalities employed, a conservative, but hopefully more rational, treatment for these lesions is recommended. Although uncommon, this problem always must be considered in the differential diagnosis of the young patient, especially female, who presents with visceral or peripheral arterial insufficiency."} {"id": "PMID:1265672", "title": "Reversibility of severe hepatic damage caused by jejunoileal bypass after re-establishment of normal intestinal continuity.", "content": "This case report attempts to document the reversibility of advanced hepatic anatomical and clinical alterations compatible with advanced hepatic cirrhosis that occasionally develop in patients with jejunoileal bypass performed for morbid obesity. The advanced stage of this complication can be fatal unless the intestinal continuity is returned to normal.", "contents": "Reversibility of severe hepatic damage caused by jejunoileal bypass after re-establishment of normal intestinal continuity. This case report attempts to document the reversibility of advanced hepatic anatomical and clinical alterations compatible with advanced hepatic cirrhosis that occasionally develop in patients with jejunoileal bypass performed for morbid obesity. The advanced stage of this complication can be fatal unless the intestinal continuity is returned to normal."} {"id": "PMID:1265726", "title": "[Oesophagotracheal fistula in a calf. Report of a case (author's transl)].", "content": "The case of a nine-month-old Dutch-Friesian heifer calf with an oesophagotracheal fistula which probably was congenital, is reported. The fistula passed obliquely from the caudodorsal to the cranioventral region, from the ventral portion of the oesophagus to the dorsal part of the trachea, into which it opened at a point one cm. cranial to the eparterial bronchus. The animal had been affected with bloat at birth and had had difficulty in drinking as a young calf. It did not show any clinical symptoms during the grazing period. It was not until the animal was housed at an age of nine months that bloat recurred as a result of inflation of the rumen by the fistula.", "contents": "[Oesophagotracheal fistula in a calf. Report of a case (author's transl)]. The case of a nine-month-old Dutch-Friesian heifer calf with an oesophagotracheal fistula which probably was congenital, is reported. The fistula passed obliquely from the caudodorsal to the cranioventral region, from the ventral portion of the oesophagus to the dorsal part of the trachea, into which it opened at a point one cm. cranial to the eparterial bronchus. The animal had been affected with bloat at birth and had had difficulty in drinking as a young calf. It did not show any clinical symptoms during the grazing period. It was not until the animal was housed at an age of nine months that bloat recurred as a result of inflation of the rumen by the fistula."} {"id": "PMID:1265727", "title": "[Hygiene in the rearing of piglets. A study of the effect of hygiene and the bacterial content of drinking-water and feed of baby pigs on a number of health and performance characteristics on pig-breeding farms (author's transl)].", "content": "The effect of hygiene on health characteristics and performance was studied on 143 farms. In addition to subjective evaluations, the bacterial counts in the drink-water and feed were adopted as criteria of hygiene. In from 6 to 27 per cent of the cases, variations in bacterial counts were associated with variations in hygiene. Bacterial counts on a single farm varied markedly. Hygiene is to a large extent determined by the attendant. On the farms, including those on which hygiene is adequate, there is a marked increase in the number of bacteria present in the drinking-water and feed of the baby pigs. The state of hygiene of the drinking water and feed is highly unsatisfactory on a large number of farms. Of all litters, 15.08 per cent developed scouring in the first week of life, 21.69 per cent showed scouring during the third week and scouring was observed in 2.24 per cent of the weaned piglets. Correlations between the various aspects hygiene are high. Improvements in farm and drinking-water hygiene are associated with a more rapid growth of the piglets. The incidence of scouring during the third week is lower on those farms on which hygiene is satisfactory. The present study showed that there was no relationship between hygiene and litter size. Early supplementary feeding does not produce any improvement in growth of the piglets. The incidence of scouring in the third week increases and growth decreases as the bacterial count in the drinking-water increases. Clean drinking-water should be available to the animals.", "contents": "[Hygiene in the rearing of piglets. A study of the effect of hygiene and the bacterial content of drinking-water and feed of baby pigs on a number of health and performance characteristics on pig-breeding farms (author's transl)]. The effect of hygiene on health characteristics and performance was studied on 143 farms. In addition to subjective evaluations, the bacterial counts in the drink-water and feed were adopted as criteria of hygiene. In from 6 to 27 per cent of the cases, variations in bacterial counts were associated with variations in hygiene. Bacterial counts on a single farm varied markedly. Hygiene is to a large extent determined by the attendant. On the farms, including those on which hygiene is adequate, there is a marked increase in the number of bacteria present in the drinking-water and feed of the baby pigs. The state of hygiene of the drinking water and feed is highly unsatisfactory on a large number of farms. Of all litters, 15.08 per cent developed scouring in the first week of life, 21.69 per cent showed scouring during the third week and scouring was observed in 2.24 per cent of the weaned piglets. Correlations between the various aspects hygiene are high. Improvements in farm and drinking-water hygiene are associated with a more rapid growth of the piglets. The incidence of scouring during the third week is lower on those farms on which hygiene is satisfactory. The present study showed that there was no relationship between hygiene and litter size. Early supplementary feeding does not produce any improvement in growth of the piglets. The incidence of scouring in the third week increases and growth decreases as the bacterial count in the drinking-water increases. Clean drinking-water should be available to the animals."} {"id": "PMID:1265728", "title": "[Food poisoning following consumption of canned meat prepared by a butcher (author's transl)].", "content": "A case of food poisoning possibly caused by the ingestion of canned meat is reported. Large numbers of micro-organisms (approximately 10(7)/gram), mainly Enterobacteriaceae and streptococci, were isolated from the contents of three cans. The contents of another can contained approximately 10(5) Bacillus spp. per gram. The meat preserves had been prepared in a butcher's shop and heated in a \"cooking pot\", the steam holes of which had been stopped up and the lid of which had been made heavier in order to reach a temperature above 100 degrees C. Inadequate sterilization and errors in processing are suggested as possible causes.", "contents": "[Food poisoning following consumption of canned meat prepared by a butcher (author's transl)]. A case of food poisoning possibly caused by the ingestion of canned meat is reported. Large numbers of micro-organisms (approximately 10(7)/gram), mainly Enterobacteriaceae and streptococci, were isolated from the contents of three cans. The contents of another can contained approximately 10(5) Bacillus spp. per gram. The meat preserves had been prepared in a butcher's shop and heated in a \"cooking pot\", the steam holes of which had been stopped up and the lid of which had been made heavier in order to reach a temperature above 100 degrees C. Inadequate sterilization and errors in processing are suggested as possible causes."} {"id": "PMID:1265731", "title": "[Use of prostaglandins in suboestrus cows (author's transl)].", "content": "One hundred and fifty lactating, suboestrus cows with palpable corpora lutea from twenty herds were treated by intramuscular injection of prostaglandins. The expected date of oestrus was predicted in 150 suboestrous controls of the same herds on the basis of ovarian findings. The average interval between treatment and insemination was 8.8 days in the prostaglandin-treated and 17.6 days in the control group. The interval between treatment and insemination was shorter than eight days in 74 per cent of the prostaglandin-treated cows. Pregnancy rates in the treatment and control groups were 56 per cent and 58 per cent respectively.", "contents": "[Use of prostaglandins in suboestrus cows (author's transl)]. One hundred and fifty lactating, suboestrus cows with palpable corpora lutea from twenty herds were treated by intramuscular injection of prostaglandins. The expected date of oestrus was predicted in 150 suboestrous controls of the same herds on the basis of ovarian findings. The average interval between treatment and insemination was 8.8 days in the prostaglandin-treated and 17.6 days in the control group. The interval between treatment and insemination was shorter than eight days in 74 per cent of the prostaglandin-treated cows. Pregnancy rates in the treatment and control groups were 56 per cent and 58 per cent respectively."} {"id": "PMID:1265732", "title": "T system in ascidian muscle: organization of the sarcotubular system in the caudal muscle cells of Botryllus schlosseri tadpole larvae.", "content": "The organization of the sarcotubular system has been examined in the caudal muscle cells of the ascidian. Botryllus schlosseri. At variance with striated muscle of other protochordates. Botryllus muscle cells are endowed with a well-developed T system, which has a peculiar laminar structure. The thin T laminae are in continuity with the plasma membrane and extend longitudinally in the intermyofibrillar spaces. At the level of the I-band the T laminae are focally associated with SR cisternae in dyad junctions similar to those observed in invertebrate muscles. These findings are discussed in relation to the origin of the sarcotubular system in vertebrate muscle.", "contents": "T system in ascidian muscle: organization of the sarcotubular system in the caudal muscle cells of Botryllus schlosseri tadpole larvae. The organization of the sarcotubular system has been examined in the caudal muscle cells of the ascidian. Botryllus schlosseri. At variance with striated muscle of other protochordates. Botryllus muscle cells are endowed with a well-developed T system, which has a peculiar laminar structure. The thin T laminae are in continuity with the plasma membrane and extend longitudinally in the intermyofibrillar spaces. At the level of the I-band the T laminae are focally associated with SR cisternae in dyad junctions similar to those observed in invertebrate muscles. These findings are discussed in relation to the origin of the sarcotubular system in vertebrate muscle."} {"id": "PMID:1265733", "title": "Structure of the epithelial - mesenchymal interface during early morphogenesis of the chick duodenum.", "content": "During the period of early morphogenetic folding of the intestinal epithelium, changes in the epithelial-mesenchymal interface were observed by light microscopy, scanning and transmission electron microscopy. The epithelium in cross-section, appears first as a circle, then an ellipse and finally by a triangle prior to the formation of the first three previllous ridges. The bases of all epithelial cells are flat at the circular stage. At the ellipse and triangle stages the bases of the epithelial cells occupying the sides possess lobopodia that do not penetrate the basal lamina. The immediate mesenchymal cells subjacent to those epithelial cells on the sides of the ellipse and triangle alter their orientation to being rounded-up or perpendicular to the plane of the basal lamina. Large numbers of fine mesenchymal pseudopodia in addition to many extracellular fibrils are revealed by transmission and scanning electron microscopy at the epithelial-mesenchymal interface. The fine mesenchymal pseudopodia come into close contact but do not penetrate the ruthenium red-staining basal lamina. The possible roles of close contact between epithelium and mesenchyme, the alteration in orientation of mesenchyme cells, and of the basal lamina in tissue interaction are discussed.", "contents": "Structure of the epithelial - mesenchymal interface during early morphogenesis of the chick duodenum. During the period of early morphogenetic folding of the intestinal epithelium, changes in the epithelial-mesenchymal interface were observed by light microscopy, scanning and transmission electron microscopy. The epithelium in cross-section, appears first as a circle, then an ellipse and finally by a triangle prior to the formation of the first three previllous ridges. The bases of all epithelial cells are flat at the circular stage. At the ellipse and triangle stages the bases of the epithelial cells occupying the sides possess lobopodia that do not penetrate the basal lamina. The immediate mesenchymal cells subjacent to those epithelial cells on the sides of the ellipse and triangle alter their orientation to being rounded-up or perpendicular to the plane of the basal lamina. Large numbers of fine mesenchymal pseudopodia in addition to many extracellular fibrils are revealed by transmission and scanning electron microscopy at the epithelial-mesenchymal interface. The fine mesenchymal pseudopodia come into close contact but do not penetrate the ruthenium red-staining basal lamina. The possible roles of close contact between epithelium and mesenchyme, the alteration in orientation of mesenchyme cells, and of the basal lamina in tissue interaction are discussed."} {"id": "PMID:1265734", "title": "A scanning electron microscope study of mouse peritoneal mesothelium.", "content": "As seen in the scanning electron microscope, peritoneal mesothelial cells of the mouse diaphragm, anterior abdominal wall and intestinal serosa carry numerous microvilli. These microvilli are absent over certain areas of the cell surface and are sometimes, interlocked in meshwork patterns or coronal formation. The apical cell membranes of the mesothelium at the base of the microvilli, are invaginated by many plasmalemmal vesicles and vacuoles and carry a number of protruding spherical structures. Deep circular craters, giving the impression of stomata, are also visible.", "contents": "A scanning electron microscope study of mouse peritoneal mesothelium. As seen in the scanning electron microscope, peritoneal mesothelial cells of the mouse diaphragm, anterior abdominal wall and intestinal serosa carry numerous microvilli. These microvilli are absent over certain areas of the cell surface and are sometimes, interlocked in meshwork patterns or coronal formation. The apical cell membranes of the mesothelium at the base of the microvilli, are invaginated by many plasmalemmal vesicles and vacuoles and carry a number of protruding spherical structures. Deep circular craters, giving the impression of stomata, are also visible."} {"id": "PMID:1265735", "title": "Observations on the olfactory organ of adult and juvenile Octopus joubini.", "content": "The olfactory organ has an epithelium containing many sense cells and a large subepithelial mass of receptor cells. The epithelium includes cells with cup-shaped, ciliated endings, and hollow, flask-shaped sense cells with ciliated cavities that open to the surface, through a small pore. Below the epithelium are large hollow cells with ciliated cavities and distal processes that either form patent connections between the ciliated cavity and the surface or have a ciliated ending at the surface. There are many synapses between processes in the olfactory nerve. The possible chemosensory function of the olfactory organ is discussed.", "contents": "Observations on the olfactory organ of adult and juvenile Octopus joubini. The olfactory organ has an epithelium containing many sense cells and a large subepithelial mass of receptor cells. The epithelium includes cells with cup-shaped, ciliated endings, and hollow, flask-shaped sense cells with ciliated cavities that open to the surface, through a small pore. Below the epithelium are large hollow cells with ciliated cavities and distal processes that either form patent connections between the ciliated cavity and the surface or have a ciliated ending at the surface. There are many synapses between processes in the olfactory nerve. The possible chemosensory function of the olfactory organ is discussed."} {"id": "PMID:1265736", "title": "Fine structure of the epidermis of the optic tentacle in a slug, Limax flavus L.", "content": "The epidermis at the tip of the optic tentacle in Limax flavus is constructed of columnar epithelial cells, distal processes of nerve cells, and scattered processes of the collar cells. The epithelial cells extend stout microvilli called plasmatic processes by Wright perpendicularly from the free surface. Each plasmic process branches into a few terminal twigs embedded in a fuzzy filamentous substance. Most nerve cells have their nuclei under the basal lamina. The distal processes of these nerve cells reach the free surface and send long microvilli to form the spongy layer under a filamentous covering. At the side surface of the tentacle the epithelial cells are cuboidal or squamous and the neural elements are fewer. Here, no spongy layer is formed; and the collar cell processes are replaced by the lateral cell processes. Peculiar secretion granules are contained in the lateral and collar cell processes as well as in their cell bodies situated beneath the basal lamina.", "contents": "Fine structure of the epidermis of the optic tentacle in a slug, Limax flavus L. The epidermis at the tip of the optic tentacle in Limax flavus is constructed of columnar epithelial cells, distal processes of nerve cells, and scattered processes of the collar cells. The epithelial cells extend stout microvilli called plasmatic processes by Wright perpendicularly from the free surface. Each plasmic process branches into a few terminal twigs embedded in a fuzzy filamentous substance. Most nerve cells have their nuclei under the basal lamina. The distal processes of these nerve cells reach the free surface and send long microvilli to form the spongy layer under a filamentous covering. At the side surface of the tentacle the epithelial cells are cuboidal or squamous and the neural elements are fewer. Here, no spongy layer is formed; and the collar cell processes are replaced by the lateral cell processes. Peculiar secretion granules are contained in the lateral and collar cell processes as well as in their cell bodies situated beneath the basal lamina."} {"id": "PMID:1265737", "title": "Localization of monoamine nerve fibres by formaldehyde fluorescence histochemistry in the posterior salivary duct and gland of Octopus vulgaris.", "content": "A bright yellow-green specific fluorescence is induced by formaldehyde histochemistry for monoamines in the secretory nerve trunks of the Octopus vulgaris posterior salivary duct, and in their ramification in the gland tubules. In contrast, the motor nerve trunks of the duct contain few fluorescent elements. The muscular and connective coat of the duct is provided with fluorescent globular and varicose structures, of various sizes and colours, which become numerous in the duct branches. At least some of these peripheral structures belong to varicose monoamine nerve fibres. In the gland, on the contrary, the muscle cells surrounding the tubules are not supplied with fluorescent nerve fibres.", "contents": "Localization of monoamine nerve fibres by formaldehyde fluorescence histochemistry in the posterior salivary duct and gland of Octopus vulgaris. A bright yellow-green specific fluorescence is induced by formaldehyde histochemistry for monoamines in the secretory nerve trunks of the Octopus vulgaris posterior salivary duct, and in their ramification in the gland tubules. In contrast, the motor nerve trunks of the duct contain few fluorescent elements. The muscular and connective coat of the duct is provided with fluorescent globular and varicose structures, of various sizes and colours, which become numerous in the duct branches. At least some of these peripheral structures belong to varicose monoamine nerve fibres. In the gland, on the contrary, the muscle cells surrounding the tubules are not supplied with fluorescent nerve fibres."} {"id": "PMID:1265738", "title": "The form of the globiferous pedicellarial ossicles of the regular echinoid, Psammechinus miliaris Gmelin.", "content": "The form of the globiferous pedicellariae from Psammechinus miliaris is described. The valve ossicle resembles that of Parechinus in its triangular valve shape and open blade form, contrasting with Echinus in these features. The present study indicates that the relationship of the valve nerve pathway to the skeletal ossicle is related to the form of the distal blade. It is proposed that subterminal teeth or a tubular blade may be alternative structural devices for strengthening the venom tooth during venom injection.", "contents": "The form of the globiferous pedicellarial ossicles of the regular echinoid, Psammechinus miliaris Gmelin. The form of the globiferous pedicellariae from Psammechinus miliaris is described. The valve ossicle resembles that of Parechinus in its triangular valve shape and open blade form, contrasting with Echinus in these features. The present study indicates that the relationship of the valve nerve pathway to the skeletal ossicle is related to the form of the distal blade. It is proposed that subterminal teeth or a tubular blade may be alternative structural devices for strengthening the venom tooth during venom injection."} {"id": "PMID:1265739", "title": "Histopathological studies on intrahepatic bile ducts in the vicinity of porta hepatis in biliary atresia.", "content": "Intrahepatic bile ducts in the vicinity of the porta hepatis were histologically investigated in 9 cases of biliary atresia and the pattern of bile duct was divided into two groups. In the first group, there were a few large bile ducts which had continuity to the extrahepatic bile duct. In the second group, many small bile ducts were histologically observed, but there was no large bile duct at the porta hepatis. This type of abnormal bile ducts was seen in the cases of obliteration of bile ducts at porta hepatis.", "contents": "Histopathological studies on intrahepatic bile ducts in the vicinity of porta hepatis in biliary atresia. Intrahepatic bile ducts in the vicinity of the porta hepatis were histologically investigated in 9 cases of biliary atresia and the pattern of bile duct was divided into two groups. In the first group, there were a few large bile ducts which had continuity to the extrahepatic bile duct. In the second group, many small bile ducts were histologically observed, but there was no large bile duct at the porta hepatis. This type of abnormal bile ducts was seen in the cases of obliteration of bile ducts at porta hepatis."} {"id": "PMID:1265740", "title": "A competitive protein binding assay for plasma 25-hydroxyvitamin D3 in normal children.", "content": "In order to determine the plasma level of 25-hydroxyvitamin D3 (25-OH-D3) in Japanese children by the competitive protein binding assay, we studied binding proteins in D-deficient rats, and obtained the following results. 1) By using serum and kidney cytosol of D-deficient rats, we could obtain a standard curve with high sensitivity and accuracy which enabled us to determine the 25-OH-D3 level ranging from 0.5 to 5.0 ng. 2) The plasma 25-OH-D3 level was found to be 21.6+/-10.1 ng/ml (n=17) in healthy infants and children from 1 to 15 year-old, and 11.4+/-8.6 ng/ml (n=27) in mature neonates up to 2 days after delivery.", "contents": "A competitive protein binding assay for plasma 25-hydroxyvitamin D3 in normal children. In order to determine the plasma level of 25-hydroxyvitamin D3 (25-OH-D3) in Japanese children by the competitive protein binding assay, we studied binding proteins in D-deficient rats, and obtained the following results. 1) By using serum and kidney cytosol of D-deficient rats, we could obtain a standard curve with high sensitivity and accuracy which enabled us to determine the 25-OH-D3 level ranging from 0.5 to 5.0 ng. 2) The plasma 25-OH-D3 level was found to be 21.6+/-10.1 ng/ml (n=17) in healthy infants and children from 1 to 15 year-old, and 11.4+/-8.6 ng/ml (n=27) in mature neonates up to 2 days after delivery."} {"id": "PMID:1265741", "title": "Effects of pentazocine on coronary hemodynamics under pentobarbital or chloralose-urethane anesthesia in dogs.", "content": "The effect of pentazocine on the coronary hemodynamics was studied in anesthetized dogs. Under pentobarbital anesthesia pentazocine did not cause any significant changes in the coronary hemodynamics. Under chloralose-urethane anesthesia, however, it produced a statistically significant increase in heart rate, left coronary blood flow rate, myocardial oxygen consumption as well as myocardial oxygen extraction rate, but a decrease in coronary vascular resistance. These results indicate that the effects of pentazocine on the coronary hemodynamics are modified significantly by the drugs used for basal anesthesia.", "contents": "Effects of pentazocine on coronary hemodynamics under pentobarbital or chloralose-urethane anesthesia in dogs. The effect of pentazocine on the coronary hemodynamics was studied in anesthetized dogs. Under pentobarbital anesthesia pentazocine did not cause any significant changes in the coronary hemodynamics. Under chloralose-urethane anesthesia, however, it produced a statistically significant increase in heart rate, left coronary blood flow rate, myocardial oxygen consumption as well as myocardial oxygen extraction rate, but a decrease in coronary vascular resistance. These results indicate that the effects of pentazocine on the coronary hemodynamics are modified significantly by the drugs used for basal anesthesia."} {"id": "PMID:1265742", "title": "Indication of mediastinal lymph nodes metastases by radioaerosol inhalation lung scanning in pulmonary neoplasm.", "content": "Fifty-three patients with pulmonary neoplasm were studied by radioaerosol inhalation and perfusion lung scans, bronchoscopy and spirometry. The probability of lymph node metastases could be estimated by the amount of inhaled aerosol deposited at the carina. On thoracotomy, actual mediastinal lymphadenopathy was minimum, if any, in 4 patients without carinal aerosol deposition. Application of the aerosol inhalation lung scan to pulmonary neoplasm provides useful diagnostic and prognostic information regarding mediastinal lymph nodes metastases.", "contents": "Indication of mediastinal lymph nodes metastases by radioaerosol inhalation lung scanning in pulmonary neoplasm. Fifty-three patients with pulmonary neoplasm were studied by radioaerosol inhalation and perfusion lung scans, bronchoscopy and spirometry. The probability of lymph node metastases could be estimated by the amount of inhaled aerosol deposited at the carina. On thoracotomy, actual mediastinal lymphadenopathy was minimum, if any, in 4 patients without carinal aerosol deposition. Application of the aerosol inhalation lung scan to pulmonary neoplasm provides useful diagnostic and prognostic information regarding mediastinal lymph nodes metastases."} {"id": "PMID:1265770", "title": "Hemodynamic effects of aerosol propellants. III. Vascular resistance in the canine hind limb.", "content": "The question as to whether or not the hypotension observed as part of the effect of tricholorofluoromethane (FC11), dichlorofluoromethane (FC 12), dichlorotetrafluoroethane (FC 114) and methyl chloroform was due to a vasodepressor component of action, in addition to the previously documented depression in myocardial contractile force, was answered by testing these agents in an anesthetized dog preparation in which one hind limb was perfused at constant flow through the femoral artery. 5% FC 11, 20% FC 12 and 20% FC 114 decreased vascular resistance of the perfused limb, as reflected by decrease in mean femoral arterial perfusion pressure, in vagotomized but not in intact preparations. Methyl chloroform decreased vascular resistance even in intact preparations. Spontaneous blood flow in the intact femoral artery decreased following FC 11 and methyl chloroform administration in vagotomized preparations and was associated with marked decrease in mean aortic pressure. Blockade of alpha and beta adrenergic receptors with phentolamine and propranolol in the vagotomized preparation had no modifying influence of the effect of FC 11 and methyl chloroform. It may be concluded from this study that FC 11, FC 12 and FC 114 exhibit a vasodepressor activity on skeletal muscle vascular bed which is readily overcome by the hypotension-induced activation of the sympathetic system but which becomes evident when reflex activity is prevented by vagotomy. Methly choloroform exhibits a vasodepressor effect even in intact preparations probably because of concomitant depression of reflex activity through its general anesthetic action. A decrease in spontaneous femoral blood flow following FC 11 and methyl chloroform administration is referable to the accompanying severe hypotension notwithstanding concomitant vascular relaxation. Neither FC 11 nor methly chloroform directly liberate catecholamines from their sites of storage.", "contents": "Hemodynamic effects of aerosol propellants. III. Vascular resistance in the canine hind limb. The question as to whether or not the hypotension observed as part of the effect of tricholorofluoromethane (FC11), dichlorofluoromethane (FC 12), dichlorotetrafluoroethane (FC 114) and methyl chloroform was due to a vasodepressor component of action, in addition to the previously documented depression in myocardial contractile force, was answered by testing these agents in an anesthetized dog preparation in which one hind limb was perfused at constant flow through the femoral artery. 5% FC 11, 20% FC 12 and 20% FC 114 decreased vascular resistance of the perfused limb, as reflected by decrease in mean femoral arterial perfusion pressure, in vagotomized but not in intact preparations. Methyl chloroform decreased vascular resistance even in intact preparations. Spontaneous blood flow in the intact femoral artery decreased following FC 11 and methyl chloroform administration in vagotomized preparations and was associated with marked decrease in mean aortic pressure. Blockade of alpha and beta adrenergic receptors with phentolamine and propranolol in the vagotomized preparation had no modifying influence of the effect of FC 11 and methyl chloroform. It may be concluded from this study that FC 11, FC 12 and FC 114 exhibit a vasodepressor activity on skeletal muscle vascular bed which is readily overcome by the hypotension-induced activation of the sympathetic system but which becomes evident when reflex activity is prevented by vagotomy. Methly choloroform exhibits a vasodepressor effect even in intact preparations probably because of concomitant depression of reflex activity through its general anesthetic action. A decrease in spontaneous femoral blood flow following FC 11 and methyl chloroform administration is referable to the accompanying severe hypotension notwithstanding concomitant vascular relaxation. Neither FC 11 nor methly chloroform directly liberate catecholamines from their sites of storage."} {"id": "PMID:1265771", "title": "Studies on the in vitro metabolism of dimethylnitrosamine by rat liver.", "content": "The biotransformation of dimethylnitrosamine (DMN) to formaldehyde, generally attributed to the mediation of a demethylase enzyme associated with the microsomal mixed function oxidase system, has been investigated in rat liver preparations. All of the enzyme activity was found in the postmitochondrial fraction and the microsomes contained approximately 50% of this activity. The restoration of total activity resulting from the addition of the cytosol to the microsomal fraction was found to be due to presence of diffusible, heat-labile constituents in the cytosol. Enzyme kinetic studies revealed that DMN was metabolized to formaldehyde by either a multistep or a multicomponent process. DMN demethylase was found to be relatively stable to storage in contrast to cytochrome P-450 and a number of mixed function oxidase enzyme activities. In spectral interaction studies DMN was found to form an atypical interaction spertrum with either control, phenobarbitone-pretreated or phospholipid-depted microsomal preparations. DMN had little effect on Type II spectral interaction of aniline, but noncompetitvely inhibited the Type I spectral interaction of benzphetamine and biphenyl. Whilst the mixed function oxidase enzyme inhibitors SKF 525A and metyrapone markedly reduced the metabolism of ethylmorphine and anailine, DMN demethylase was little affected by the former compound and appreciably enhanced by metyrapone. Moreover, DMN demethylase was strongly inhibited a number of hepatic mixed function oxidases, but significantly reduced anaerobic nitroreductase activity. The results of these studies reveal important differences between the properties of the enzymatic systems which metabolize DMN and mixed function oxidase substrates, and are consistent with the conclusion that the degradation of DMN to formaldehyde by rat liver preparations is a multicomponent system not rate limiting with respect to cytochrome P-450.", "contents": "Studies on the in vitro metabolism of dimethylnitrosamine by rat liver. The biotransformation of dimethylnitrosamine (DMN) to formaldehyde, generally attributed to the mediation of a demethylase enzyme associated with the microsomal mixed function oxidase system, has been investigated in rat liver preparations. All of the enzyme activity was found in the postmitochondrial fraction and the microsomes contained approximately 50% of this activity. The restoration of total activity resulting from the addition of the cytosol to the microsomal fraction was found to be due to presence of diffusible, heat-labile constituents in the cytosol. Enzyme kinetic studies revealed that DMN was metabolized to formaldehyde by either a multistep or a multicomponent process. DMN demethylase was found to be relatively stable to storage in contrast to cytochrome P-450 and a number of mixed function oxidase enzyme activities. In spectral interaction studies DMN was found to form an atypical interaction spertrum with either control, phenobarbitone-pretreated or phospholipid-depted microsomal preparations. DMN had little effect on Type II spectral interaction of aniline, but noncompetitvely inhibited the Type I spectral interaction of benzphetamine and biphenyl. Whilst the mixed function oxidase enzyme inhibitors SKF 525A and metyrapone markedly reduced the metabolism of ethylmorphine and anailine, DMN demethylase was little affected by the former compound and appreciably enhanced by metyrapone. Moreover, DMN demethylase was strongly inhibited a number of hepatic mixed function oxidases, but significantly reduced anaerobic nitroreductase activity. The results of these studies reveal important differences between the properties of the enzymatic systems which metabolize DMN and mixed function oxidase substrates, and are consistent with the conclusion that the degradation of DMN to formaldehyde by rat liver preparations is a multicomponent system not rate limiting with respect to cytochrome P-450."} {"id": "PMID:1265772", "title": "Chronic toxicity of methylmercury in the adult cat. Interim report.", "content": "Doses of 3, 8.4, 20, 46, 74 or 176 mug Hg/kg/day were fed to groups of 8--10 adult cats, either as methylmercuric chloride or as methylmercury-contaminated fish, 7 days/week for up to 2 years. Food consumption, body weight change, blood mercury levels, haematology, urine analysis, serum blood urea nitrogen (BUN) levels and neurological status were assessed regularly in all animals. Clinical signs of methylmercury toxicity -- consisting of ataxia, loss of balance and motor incorrdination -- occured in groups receiving 176 mug Hg/kg/day after 14 weeks of treatment. Pathological findings were confined to the nervous system and consisted of loss of nerve cells with replacement by reactive and fibrillary gloisis. Terminal blood and brain mercury levels were approx. 10 ppm. There were no differences in the time required to develop clinical signs of methylmercury toxicity, tissue mercury levels or pathology between the groups of cats receiving methylmercury as methylmercuric chloride or as methylmercury-contaminated fish, at either dose level. Blood mercury levels in the remaining doses groups appeared to plateau after 40 weeks of treatment. Groups receiving 46 mug Hg/kg/day began to show some neurological impairment after 60 weeks of treatment which did not progress in subsequent weeks. No treatment-related effects were present in groups receiving 20, 8.4 or 3 mug Hg/kg/day after 2 years.", "contents": "Chronic toxicity of methylmercury in the adult cat. Interim report. Doses of 3, 8.4, 20, 46, 74 or 176 mug Hg/kg/day were fed to groups of 8--10 adult cats, either as methylmercuric chloride or as methylmercury-contaminated fish, 7 days/week for up to 2 years. Food consumption, body weight change, blood mercury levels, haematology, urine analysis, serum blood urea nitrogen (BUN) levels and neurological status were assessed regularly in all animals. Clinical signs of methylmercury toxicity -- consisting of ataxia, loss of balance and motor incorrdination -- occured in groups receiving 176 mug Hg/kg/day after 14 weeks of treatment. Pathological findings were confined to the nervous system and consisted of loss of nerve cells with replacement by reactive and fibrillary gloisis. Terminal blood and brain mercury levels were approx. 10 ppm. There were no differences in the time required to develop clinical signs of methylmercury toxicity, tissue mercury levels or pathology between the groups of cats receiving methylmercury as methylmercuric chloride or as methylmercury-contaminated fish, at either dose level. Blood mercury levels in the remaining doses groups appeared to plateau after 40 weeks of treatment. Groups receiving 46 mug Hg/kg/day began to show some neurological impairment after 60 weeks of treatment which did not progress in subsequent weeks. No treatment-related effects were present in groups receiving 20, 8.4 or 3 mug Hg/kg/day after 2 years."} {"id": "PMID:1265773", "title": "Distribution of aflatoxin B1 in tissues of mink (Mustela vison).", "content": "Seven female mink (Mustela vison) were injected intraperitoneally with a single dose of 100 mug aflatoxin B1 (14 C-label and unabeled). They were sacrificed 1, 2, 4, and 24 h after dosing. Liver, instestines, stomach, lung, kidney, brain, pancrease, spleen, urinary bladder, uterus, and bile were removed and examined for the retained radioactivity. 1 h after dosing, intestines and their contents retained the largest amount of 14C-radioacivity (18.9% of the amount that was administered) which was followed by liver (13.2%) and the bile (10.8%). At this time all other tissues retained less than 1% of the administered radioactivity. Generally, the amount of radioactivity retained in all tissues declined with time. Only 1.2 and 0.6% of the administered radioactivity was found in testines and bile, respectively, 24 h after dosing; however, the liver still contained 6.6% of the initial radioactivity. Examination of subcellular fractions of liver revealed that at all time intervals most of the radioactivity was associated with the micrososmal supernatant fluid.", "contents": "Distribution of aflatoxin B1 in tissues of mink (Mustela vison). Seven female mink (Mustela vison) were injected intraperitoneally with a single dose of 100 mug aflatoxin B1 (14 C-label and unabeled). They were sacrificed 1, 2, 4, and 24 h after dosing. Liver, instestines, stomach, lung, kidney, brain, pancrease, spleen, urinary bladder, uterus, and bile were removed and examined for the retained radioactivity. 1 h after dosing, intestines and their contents retained the largest amount of 14C-radioacivity (18.9% of the amount that was administered) which was followed by liver (13.2%) and the bile (10.8%). At this time all other tissues retained less than 1% of the administered radioactivity. Generally, the amount of radioactivity retained in all tissues declined with time. Only 1.2 and 0.6% of the administered radioactivity was found in testines and bile, respectively, 24 h after dosing; however, the liver still contained 6.6% of the initial radioactivity. Examination of subcellular fractions of liver revealed that at all time intervals most of the radioactivity was associated with the micrososmal supernatant fluid."} {"id": "PMID:1265774", "title": "Long-term toxicity of the surfactant alpha-olefin sulphonate (AOS) in the rat.", "content": "The surfactant alpha-olefin sulphonate (AOS) was fed to rats at dietary levels of 1000, 2500 and 5000 ppm for a period of 2 years. There were no adverse clinical signs, and survival rates were not affected by treatment with AOS. The rate of bodyweight gain was marginally lower during the second trimester of the study in both males and females receiving 5000 ppm AOS, while food intake was also marginally lower during the first year among females receiving 5000 ppm. During the remainder of the study, bodyweight change and food consumption of all treated animals was similar to that of the control animals. Investigation of the animals' eyes, blood and urine did not reveal any reaction to treatment, nor were any changes relating to treatment seen in the macroscopic pathology or organ weights of rats killed after 104 weeks. Histological examination of the tissues did not provide any evidence of toxicity or tumour induction that could be attributable to treatment with AOS.", "contents": "Long-term toxicity of the surfactant alpha-olefin sulphonate (AOS) in the rat. The surfactant alpha-olefin sulphonate (AOS) was fed to rats at dietary levels of 1000, 2500 and 5000 ppm for a period of 2 years. There were no adverse clinical signs, and survival rates were not affected by treatment with AOS. The rate of bodyweight gain was marginally lower during the second trimester of the study in both males and females receiving 5000 ppm AOS, while food intake was also marginally lower during the first year among females receiving 5000 ppm. During the remainder of the study, bodyweight change and food consumption of all treated animals was similar to that of the control animals. Investigation of the animals' eyes, blood and urine did not reveal any reaction to treatment, nor were any changes relating to treatment seen in the macroscopic pathology or organ weights of rats killed after 104 weeks. Histological examination of the tissues did not provide any evidence of toxicity or tumour induction that could be attributable to treatment with AOS."} {"id": "PMID:1265775", "title": "Short-term toxicity of 1-naphthaleneacetic acid in rats.", "content": "In a 90-day feeding study, 4 groups of 10 male and 10 female rats received in the diet 0,200, 1000 and 5000 ppm 1-naphthaleneacetic acid (1-NAA). Growth and food intake was reduced significantly only in males on 5000 ppm. Haematological examination yielded essentially negative results except for a non-significant reduction at the 1000 and 5000 ppn levels in the leucocyte count, mainly due to a reduction in neutrophils. No significant effects were observed in the renal concentration test, urinalysis, renal histochemistry or histology of a wide range of organs at any level of 1-NAA tested. Increased relative weights of thyroid, testes, brain and liver were confined to the 5000 ppm level. The increase in relative liver weight was not accompanied by histological liver damage and was associated with elevated liver microsomal enzyme activity. The loss of glucose 6-phosphatase (G6Pase) and increase in glucose 6-phosphate dehydrogenase (G6PDH) seen histochemically in the centrilobular region of the liver in males on 5000 ppm, accompanied by glycogen depletion in the liver, could however be indicative of liver damage. On the basis of conventional criteria, a no-effect level of 1000 ppm would have been indicated by this study but in view of liver glycogen depletion at all levels tested a no-effect level was not established.", "contents": "Short-term toxicity of 1-naphthaleneacetic acid in rats. In a 90-day feeding study, 4 groups of 10 male and 10 female rats received in the diet 0,200, 1000 and 5000 ppm 1-naphthaleneacetic acid (1-NAA). Growth and food intake was reduced significantly only in males on 5000 ppm. Haematological examination yielded essentially negative results except for a non-significant reduction at the 1000 and 5000 ppn levels in the leucocyte count, mainly due to a reduction in neutrophils. No significant effects were observed in the renal concentration test, urinalysis, renal histochemistry or histology of a wide range of organs at any level of 1-NAA tested. Increased relative weights of thyroid, testes, brain and liver were confined to the 5000 ppm level. The increase in relative liver weight was not accompanied by histological liver damage and was associated with elevated liver microsomal enzyme activity. The loss of glucose 6-phosphatase (G6Pase) and increase in glucose 6-phosphate dehydrogenase (G6PDH) seen histochemically in the centrilobular region of the liver in males on 5000 ppm, accompanied by glycogen depletion in the liver, could however be indicative of liver damage. On the basis of conventional criteria, a no-effect level of 1000 ppm would have been indicated by this study but in view of liver glycogen depletion at all levels tested a no-effect level was not established."} {"id": "PMID:1265776", "title": "Effect of short-term administration of lead to pregnant rats.", "content": "Lead was administred to adult female rats in drinking water (0;0.1:1 and 10 ppm) for 3 weeks before mating, during pregnancy and during 3 weeks after delivery. On day 21 after delivery the mothers and their newborns were sacrified and various parameters of blood -- lead concentration on (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins (FEP), delta0aminolevulinate dehydratase (ALAD) -- and tissue -- ALAD, free tissue porphyrins (FTP), lead concentration (Pb-T) -- were determined. In mothers a significant increase in Pb-B and Pb concentration in kidney was found in the 10 ppm group, but this increase in lead concentration was not associated with any statistically significant modification of the biochemical parameters. In newborns, lead concentration in blood and in kidney was also significantly increased in the 10 ppm group and this lead exposure was associated with a decrease of the ALAD activity in blood and an increase of FTP in kidney. On the basis of the biochemical parameters investigated one can therefore conclude that the developing organism is more susceptible to the biological action of lead than the organism of adult animals and that the \"no-effect\" level of lead administered during pregnancy and in the neonatal period is around 1 ppm.", "contents": "Effect of short-term administration of lead to pregnant rats. Lead was administred to adult female rats in drinking water (0;0.1:1 and 10 ppm) for 3 weeks before mating, during pregnancy and during 3 weeks after delivery. On day 21 after delivery the mothers and their newborns were sacrified and various parameters of blood -- lead concentration on (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins (FEP), delta0aminolevulinate dehydratase (ALAD) -- and tissue -- ALAD, free tissue porphyrins (FTP), lead concentration (Pb-T) -- were determined. In mothers a significant increase in Pb-B and Pb concentration in kidney was found in the 10 ppm group, but this increase in lead concentration was not associated with any statistically significant modification of the biochemical parameters. In newborns, lead concentration in blood and in kidney was also significantly increased in the 10 ppm group and this lead exposure was associated with a decrease of the ALAD activity in blood and an increase of FTP in kidney. On the basis of the biochemical parameters investigated one can therefore conclude that the developing organism is more susceptible to the biological action of lead than the organism of adult animals and that the \"no-effect\" level of lead administered during pregnancy and in the neonatal period is around 1 ppm."} {"id": "PMID:1265777", "title": "[Tumor inactivation and radiobiology].", "content": "In this paper, the inactivation of tumors and the tolerance of irradiated surrounding normal tissues is considered under radiobiological aspects. Surviving euoxic cells may be calculated by means of a simple exponential function being characterized by a reduction constant D0. This constant decreases with increasing single doses. Another exponential function allows the calculation of the probability of tumor destruction from the surviving fraction of tumor cells after irradiation. Examples show the probability curves steeply rising with the total dose, in accordance with former observations of Holthusen (S-curves). From the amount of total dose and the steepnees of the rise the values of radiation sensitivity of the particular cells may be evaluated. If there is a fraction of anoxic tumor cells, it is probable that after every irradiation a part of them is transformed into euoxic cells. In such a case, the recovery curves, depending on the degree of reoxygenation, will shift to larger values of the total doses. A good reoxygenation, therefore, is highly important for the success of the irradiation, it can be realized by appropriate irradiation programs. The regeneration (repopulation) of normal cells is of fundamental importance for the restitution of normal tissues following radiation injury. It is generally assumed that the tolerance dose is reached when the number of surviving normal cells arrives at a lower limit. Cohen's measurements at the skin of patients treated with 200 keV X-rays have been used for the calculation of tolerance doses for Co-60 gamma-rays and fast electrons. The tolerance doses depend on the amount of the single doses and result in calculated values of over 10000 rd with electron irradiation of 500 rd per week. These calculations are confirmed by the findings of Schumacher with electron irradiation.", "contents": "[Tumor inactivation and radiobiology]. In this paper, the inactivation of tumors and the tolerance of irradiated surrounding normal tissues is considered under radiobiological aspects. Surviving euoxic cells may be calculated by means of a simple exponential function being characterized by a reduction constant D0. This constant decreases with increasing single doses. Another exponential function allows the calculation of the probability of tumor destruction from the surviving fraction of tumor cells after irradiation. Examples show the probability curves steeply rising with the total dose, in accordance with former observations of Holthusen (S-curves). From the amount of total dose and the steepnees of the rise the values of radiation sensitivity of the particular cells may be evaluated. If there is a fraction of anoxic tumor cells, it is probable that after every irradiation a part of them is transformed into euoxic cells. In such a case, the recovery curves, depending on the degree of reoxygenation, will shift to larger values of the total doses. A good reoxygenation, therefore, is highly important for the success of the irradiation, it can be realized by appropriate irradiation programs. The regeneration (repopulation) of normal cells is of fundamental importance for the restitution of normal tissues following radiation injury. It is generally assumed that the tolerance dose is reached when the number of surviving normal cells arrives at a lower limit. Cohen's measurements at the skin of patients treated with 200 keV X-rays have been used for the calculation of tolerance doses for Co-60 gamma-rays and fast electrons. The tolerance doses depend on the amount of the single doses and result in calculated values of over 10000 rd with electron irradiation of 500 rd per week. These calculations are confirmed by the findings of Schumacher with electron irradiation."} {"id": "PMID:1265778", "title": "[Histological diagnosis of gynecologic recurrences in the minor pelvis. Puncture using the tru-cut biopsy needle].", "content": "In about 60 cases demonstrating a tentative diagnosis of a palpable recidivation (cancer of the cervix), a puncture of the parametrium and of the pelvic wall was carried out with the biopsy needle \"Tru-Cut\". The modalities of procedure are described. Verification of cancer suspicion was achieved to a rate of 50 per cent, this percentage having increased for about 20% when the puncture was repeated. Ten per cent of the carcinomas could not be listed, and in 20% of the cases a recidivation could be excluded. There were no complications.", "contents": "[Histological diagnosis of gynecologic recurrences in the minor pelvis. Puncture using the tru-cut biopsy needle]. In about 60 cases demonstrating a tentative diagnosis of a palpable recidivation (cancer of the cervix), a puncture of the parametrium and of the pelvic wall was carried out with the biopsy needle \"Tru-Cut\". The modalities of procedure are described. Verification of cancer suspicion was achieved to a rate of 50 per cent, this percentage having increased for about 20% when the puncture was repeated. Ten per cent of the carcinomas could not be listed, and in 20% of the cases a recidivation could be excluded. There were no complications."} {"id": "PMID:1265779", "title": "[Vaginal applicator combination for radium therapy of advanced vaginal and cervix carcinomas].", "content": "A vaginal applicator combination for intracavitary radium therapy in cancers of the female genitals was developed. By means of several stages which may be combined moreover with tube filters, different combinations and different radium quantities are applicable which can be adjusted to the results of medical examination using symmetric or asymmetric radium sources. The loading of the applicator combination is executed by straight genuine tube filters which were fixed by weld.", "contents": "[Vaginal applicator combination for radium therapy of advanced vaginal and cervix carcinomas]. A vaginal applicator combination for intracavitary radium therapy in cancers of the female genitals was developed. By means of several stages which may be combined moreover with tube filters, different combinations and different radium quantities are applicable which can be adjusted to the results of medical examination using symmetric or asymmetric radium sources. The loading of the applicator combination is executed by straight genuine tube filters which were fixed by weld."} {"id": "PMID:1265780", "title": "[Radio-chemotherapy of cervix carcinoma. I. Clinical part].", "content": "A prospective study was performed for a new model concerning the potentiation of radiation with Podophyllum (Proresid) and the radioprotection with Acethylhomocystein-thiolactone (Reducdyn) in cases of the squamous cell carcinoma of the uterine cervix. The study was carried out on the basis of alternated data of birth. The total number of the randomization was 256, consisting of 173 stages II und 83 stages III. All patients were irradiated with 6000 mgeh Ra and 4500 R 60Co. In addition to the irradiation one group of 128 patients received an infusion of 1g Podophyllum/day after irradiation. Another group of 46 patients was treated prior to irradiation with 1g Acethyl-homocystein-thiolactone (AHCT) and with Podophyllum after exposure. The total dosage was between 30 and 50g Pod. and 30 and 50g AHCT. It could be shown that the survival rate after three years was increased up to 15%. An earlier study revealed a five-year-survival rate of 23%.", "contents": "[Radio-chemotherapy of cervix carcinoma. I. Clinical part]. A prospective study was performed for a new model concerning the potentiation of radiation with Podophyllum (Proresid) and the radioprotection with Acethylhomocystein-thiolactone (Reducdyn) in cases of the squamous cell carcinoma of the uterine cervix. The study was carried out on the basis of alternated data of birth. The total number of the randomization was 256, consisting of 173 stages II und 83 stages III. All patients were irradiated with 6000 mgeh Ra and 4500 R 60Co. In addition to the irradiation one group of 128 patients received an infusion of 1g Podophyllum/day after irradiation. Another group of 46 patients was treated prior to irradiation with 1g Acethyl-homocystein-thiolactone (AHCT) and with Podophyllum after exposure. The total dosage was between 30 and 50g Pod. and 30 and 50g AHCT. It could be shown that the survival rate after three years was increased up to 15%. An earlier study revealed a five-year-survival rate of 23%."} {"id": "PMID:1265781", "title": "[Growth velocity of breast carcinoma and radiographic \"early diagnoses\"].", "content": "Between 1960 and 1975, 53 mammary carcinomas have been observed in a collective of 15000 women a part of whom, comprising finally 80 per cent, was free from troubles (annual prophylactic examination for breast cancer). Of these 53 cases were available two up to eleven preceding mammographic series made within an observation period of 0.2 to eleven years. A \"mean growth curve\" was obtained empirically, based on 163 mammographic tumor measurements with tumor sizes between 2 mm and 60 mm. In the course of a development period between two and eleven years, 33 per cent of the carcinomas were seen to accelerate their further growth in comparison with the initial value; 66 per cent revealed an increasing slow-down of growth, and all tumors showed considerable changes in their growth rates. Mammary carcinomas altogether continually decelerated their growth as measured by the duplication time of the tumor volume from Tv = 309 days on the average up to an average of Tv = 381 days after two through eleven years. The mean growth curve exhibited an exponential shape which was completed by biomathematical methods and can be described by means of a Power function. It corresponds well to the rate of incidence of the mammary carcinoma which shows an identical rise in relation to increased old age. The medium growth time from a primary cancerous cell with ten micron in size up to the tumor 2 mm in diameter may be estimated biomathematically only and amounts to ten or twenty years with 23 duplication periods. The further average growth rate between the tumor sizes of two and ten millimeter, stages which can be diagnosed roentgenologically, was empirically six years; the most quickly growing tumor needed almost two years. For the purpose of early cancer detection (tumor size below 10 mm, lymph nodes histologically free from metastases), the serial mammography to be performed every 18 months or two years is the only technique which provides utilizable early recognition marks and besides does allow a simple judgement. Solely the symptoms \"suspect desification, partly spiculated\" in sixty per cent and \"typical cancerous microcalcification\" in forty per cent have been observed as the earliest signs. The reliability (\"certainty\") of mammography is frequently overestimated (false negative rate: 7 to 18%) and should be quoted only for collectives where control mammographies have been made over a period of five or ten years. Roentgenological controls of alterations below three millimeter in size and without an indication for biopsy ought to be performed within six months, and still sooner in case of larger alterations. It is not possible earlier than after five or ten years to judge of the radicality of a therapy, as spread cancerous cells, on he average, reveal similar growth rates as does the primary tumor.", "contents": "[Growth velocity of breast carcinoma and radiographic \"early diagnoses\"]. Between 1960 and 1975, 53 mammary carcinomas have been observed in a collective of 15000 women a part of whom, comprising finally 80 per cent, was free from troubles (annual prophylactic examination for breast cancer). Of these 53 cases were available two up to eleven preceding mammographic series made within an observation period of 0.2 to eleven years. A \"mean growth curve\" was obtained empirically, based on 163 mammographic tumor measurements with tumor sizes between 2 mm and 60 mm. In the course of a development period between two and eleven years, 33 per cent of the carcinomas were seen to accelerate their further growth in comparison with the initial value; 66 per cent revealed an increasing slow-down of growth, and all tumors showed considerable changes in their growth rates. Mammary carcinomas altogether continually decelerated their growth as measured by the duplication time of the tumor volume from Tv = 309 days on the average up to an average of Tv = 381 days after two through eleven years. The mean growth curve exhibited an exponential shape which was completed by biomathematical methods and can be described by means of a Power function. It corresponds well to the rate of incidence of the mammary carcinoma which shows an identical rise in relation to increased old age. The medium growth time from a primary cancerous cell with ten micron in size up to the tumor 2 mm in diameter may be estimated biomathematically only and amounts to ten or twenty years with 23 duplication periods. The further average growth rate between the tumor sizes of two and ten millimeter, stages which can be diagnosed roentgenologically, was empirically six years; the most quickly growing tumor needed almost two years. For the purpose of early cancer detection (tumor size below 10 mm, lymph nodes histologically free from metastases), the serial mammography to be performed every 18 months or two years is the only technique which provides utilizable early recognition marks and besides does allow a simple judgement. Solely the symptoms \"suspect desification, partly spiculated\" in sixty per cent and \"typical cancerous microcalcification\" in forty per cent have been observed as the earliest signs. The reliability (\"certainty\") of mammography is frequently overestimated (false negative rate: 7 to 18%) and should be quoted only for collectives where control mammographies have been made over a period of five or ten years. Roentgenological controls of alterations below three millimeter in size and without an indication for biopsy ought to be performed within six months, and still sooner in case of larger alterations. It is not possible earlier than after five or ten years to judge of the radicality of a therapy, as spread cancerous cells, on he average, reveal similar growth rates as does the primary tumor."} {"id": "PMID:1265782", "title": "[Isodose computations of linear and circular interstitial radiation sources].", "content": "A new program for computation and representation of isodoses around interstitial radiation sources is presented. The sources can be arranged in a line or circularly. The choice for the location of the isodose plane is restricted by a sole condition: It has to be positioned parallel to a given axis. The program comprises different possibilities for an optimal description of the isodoses.", "contents": "[Isodose computations of linear and circular interstitial radiation sources]. A new program for computation and representation of isodoses around interstitial radiation sources is presented. The sources can be arranged in a line or circularly. The choice for the location of the isodose plane is restricted by a sole condition: It has to be positioned parallel to a given axis. The program comprises different possibilities for an optimal description of the isodoses."} {"id": "PMID:1265783", "title": "[The action mechanism of heparin in the increase of radiation resistance of mice].", "content": "Repeated intraperitoneal heparin injections given to mice prior to a whole-body irradiation with 650 R reduce the blood coagulation time between the seventh and the 19th day after radiation injury as compared to untreated animals exposed to radiation. Controls, not having been irradiated, didn't show any measurable effect after repeated heparin administration in 60 per cent of the experimental animals, whereas in 40 per cent the hematocrit value decreased to about two thirds of the normal, this probably being caused by internal hemorrhages. The increase in radiation resistance of mice, following administration of heparin, therefore may be due to a stimulation of the hematopoietic system, beginning already before exposure.", "contents": "[The action mechanism of heparin in the increase of radiation resistance of mice]. Repeated intraperitoneal heparin injections given to mice prior to a whole-body irradiation with 650 R reduce the blood coagulation time between the seventh and the 19th day after radiation injury as compared to untreated animals exposed to radiation. Controls, not having been irradiated, didn't show any measurable effect after repeated heparin administration in 60 per cent of the experimental animals, whereas in 40 per cent the hematocrit value decreased to about two thirds of the normal, this probably being caused by internal hemorrhages. The increase in radiation resistance of mice, following administration of heparin, therefore may be due to a stimulation of the hematopoietic system, beginning already before exposure."} {"id": "PMID:1265784", "title": "[Regeneration of murine fibroblasts, L-929, following fractionated irradiation].", "content": "L-cells in culture were irradiated with single and fractionated doses of 200 kV X-rays. Dose effect curves were determined using the colony forming capacity as the criterion of the radiation effect. After an initial dose of 330 rd and a 3 h to 16 h incubation at 37 degrees C a restitution of the shoulder of the dose effect curves was observed (Elkind repair). 16 hours after preirradiation the dose effect curve showed a statistically significant increase of n and Dq as compared to the dose effect curve after single irradiations showing that the cells have become more radioresistant by the radiation pretreatment. The curve of the colony forming ability after a total dose of 660 rd given in two equal doses of 330 rd had an oscillating shape depending on the fractionation interval. This type of curve can be interpreted by the restitution progression model.", "contents": "[Regeneration of murine fibroblasts, L-929, following fractionated irradiation]. L-cells in culture were irradiated with single and fractionated doses of 200 kV X-rays. Dose effect curves were determined using the colony forming capacity as the criterion of the radiation effect. After an initial dose of 330 rd and a 3 h to 16 h incubation at 37 degrees C a restitution of the shoulder of the dose effect curves was observed (Elkind repair). 16 hours after preirradiation the dose effect curve showed a statistically significant increase of n and Dq as compared to the dose effect curve after single irradiations showing that the cells have become more radioresistant by the radiation pretreatment. The curve of the colony forming ability after a total dose of 660 rd given in two equal doses of 330 rd had an oscillating shape depending on the fractionation interval. This type of curve can be interpreted by the restitution progression model."} {"id": "PMID:1265785", "title": "[Floating rates of synchronized CHO fibroblasts following 60Co gamma irradiation].", "content": "Monolayer cell colonies normally are pushing off single cells, which go into suspension. A dose-dependent increase of these cell detachments followed by readhesion and colony forming would influence the colony survival curve. Detached cells being in suspension can be verified by means of the colony forming test after decantation and inoculation of the medium. The amount of colony forming cells in the late phase of synthesis does scarcely change following 300 rds of 60Co gamma irradiation. The diminution of cell adhesion expected as a result of radiation damage could not be observed.", "contents": "[Floating rates of synchronized CHO fibroblasts following 60Co gamma irradiation]. Monolayer cell colonies normally are pushing off single cells, which go into suspension. A dose-dependent increase of these cell detachments followed by readhesion and colony forming would influence the colony survival curve. Detached cells being in suspension can be verified by means of the colony forming test after decantation and inoculation of the medium. The amount of colony forming cells in the late phase of synthesis does scarcely change following 300 rds of 60Co gamma irradiation. The diminution of cell adhesion expected as a result of radiation damage could not be observed."} {"id": "PMID:1265786", "title": "[Animal experiment studies on the use of ozone in irradiated and non-irradiated tumors. I. Intravenous ozone therapy of Crocker's sarcoma 180 and Ehrlich carcinoma in the white mouse].", "content": "The fractionated tangential local X-ray therapy, in cases of sarcoma 180 in white mice with a total dose of 1500 R, effects a shrinking of the tumours as well as a certain number of cures. Intravenous administration of ozone in a total dose of 0.15 times 10(-7)g, 1.5 times 10(-7)g, and 15 times 10(-7)g - by itself or together with irradiation - has as consequence neither an inhibitory effect on the tumour growth, nor an increase in radiation effect that are surpassing the diffusion width of the model and are reproducible in an exact manner. It has been possible to prove an inhibition of the tumour growth in the solid Ehrlich's carcinoma of white mice after a fractionated 2000 R irradiation, but also in these cases, no effect of the ozone application was stated.", "contents": "[Animal experiment studies on the use of ozone in irradiated and non-irradiated tumors. I. Intravenous ozone therapy of Crocker's sarcoma 180 and Ehrlich carcinoma in the white mouse]. The fractionated tangential local X-ray therapy, in cases of sarcoma 180 in white mice with a total dose of 1500 R, effects a shrinking of the tumours as well as a certain number of cures. Intravenous administration of ozone in a total dose of 0.15 times 10(-7)g, 1.5 times 10(-7)g, and 15 times 10(-7)g - by itself or together with irradiation - has as consequence neither an inhibitory effect on the tumour growth, nor an increase in radiation effect that are surpassing the diffusion width of the model and are reproducible in an exact manner. It has been possible to prove an inhibition of the tumour growth in the solid Ehrlich's carcinoma of white mice after a fractionated 2000 R irradiation, but also in these cases, no effect of the ozone application was stated."} {"id": "PMID:1265787", "title": "Dominant lethals following acute spermatogonial X-irradiation in the rat.", "content": "Spermatogonial X-irradiation with 0, 400 or 600 R in adult rats and 200 R in fetal rats was carried out to assess genetic damage by the test of induced dominant lethality. From postimplantation embryonic losses observed, dominant lethal rates were established to be significantly raised by a dose of 400 or 600 R. With 200 R given either to adult or to fetal rats, no excess was detected in embryonic death rates.", "contents": "Dominant lethals following acute spermatogonial X-irradiation in the rat. Spermatogonial X-irradiation with 0, 400 or 600 R in adult rats and 200 R in fetal rats was carried out to assess genetic damage by the test of induced dominant lethality. From postimplantation embryonic losses observed, dominant lethal rates were established to be significantly raised by a dose of 400 or 600 R. With 200 R given either to adult or to fetal rats, no excess was detected in embryonic death rates."} {"id": "PMID:1265788", "title": "Preparation of 1,2-3H-21-deoxycortisol by incubation of 1,2-3H-17-hydroxyprogesterone with rat adrenal mitochondria.", "content": "A method is described for preparation of 1,2-3H-21-deoxycortisol by incubation of 1,2-3H-17-hydroxyprogesterone with rat adrenal mitoochondria. The radiochemical purity of the product was established by two subsequent chromatographies, reversed isotopic dilution and oxidation to 21-deoxycortisone. The final yield of 1,2-3H-21-deoxycortisol was approximately 15%.", "contents": "Preparation of 1,2-3H-21-deoxycortisol by incubation of 1,2-3H-17-hydroxyprogesterone with rat adrenal mitochondria. A method is described for preparation of 1,2-3H-21-deoxycortisol by incubation of 1,2-3H-17-hydroxyprogesterone with rat adrenal mitoochondria. The radiochemical purity of the product was established by two subsequent chromatographies, reversed isotopic dilution and oxidation to 21-deoxycortisone. The final yield of 1,2-3H-21-deoxycortisol was approximately 15%."} {"id": "PMID:1265789", "title": "Syntheses of estetrol monoglucuronides.", "content": "Four possible monoglucuronides of estetrol (estra-1,3,5(10)-triene-3,15 alpha, 16 alpha, 17 beta-tetraol) have been prepared from appropriately protected estetrol by the Koenigs-Knorr reaction employing cadmium carbonate as a catalyst. Condensation of methyl acetobromoglucuronate with estetrol 15,16,17-triacetate provided the 3-glucuronide acetate-methyl ester in a satisfactory yield. Introduction of the glucuronyl residue into C-17 was similarly attained by the use of estetrol 3-benzoate 15,16-acetonide. When estetrol 3,17-diacetate and acetobromosugar were stirred in anhydrous toluene in the presence of cadmium salt, the reaction occurred at C-16 and C-15 yielding two isomeric monoglucuronide derivatives in a ratio of ca. 5 to 2. Removal of the protecting groups in the four glucuronide acetate-methyl esters gave the desired estetrol glucuronides, respectively. These synthetic substrates underwent readily enzymatic hydrolysis with beef-liver beta-glucuronidase to afford estetrol.", "contents": "Syntheses of estetrol monoglucuronides. Four possible monoglucuronides of estetrol (estra-1,3,5(10)-triene-3,15 alpha, 16 alpha, 17 beta-tetraol) have been prepared from appropriately protected estetrol by the Koenigs-Knorr reaction employing cadmium carbonate as a catalyst. Condensation of methyl acetobromoglucuronate with estetrol 15,16,17-triacetate provided the 3-glucuronide acetate-methyl ester in a satisfactory yield. Introduction of the glucuronyl residue into C-17 was similarly attained by the use of estetrol 3-benzoate 15,16-acetonide. When estetrol 3,17-diacetate and acetobromosugar were stirred in anhydrous toluene in the presence of cadmium salt, the reaction occurred at C-16 and C-15 yielding two isomeric monoglucuronide derivatives in a ratio of ca. 5 to 2. Removal of the protecting groups in the four glucuronide acetate-methyl esters gave the desired estetrol glucuronides, respectively. These synthetic substrates underwent readily enzymatic hydrolysis with beef-liver beta-glucuronidase to afford estetrol."} {"id": "PMID:1265791", "title": "Metabolism of radioactive 17 beta-estradiol 3-methyl ether by humans.", "content": "A mixture of 2-3H and 4-14C-17beta-estradiol 3-methyl ether was administered orally to a man and to a woman. 34 and 35 percent of the 3H was liberated into the body water of the man and of the woman, respectively, reflecting reactions involving position 2. The metabolism of estradiol methyl ether was qualitatively similar to that observed previously for radioactive estradiol administered intravenously to the same subjects, as judged by the measurement of various urinary metabolites by reverse isotope dilution. Evidence was obtained for hydroxylation at position 2 without demethylation by the isolation of urinary 2-hydroxyestrone 3-methyl ether which retained 33% of the original 3H. This 3H was presumably at position 1, resulted from an NIH shift which does not occur during hydroxylation of estrone or estradiol. This was confirmed by subsequent administration of a mixture of 4-14C and 3H-(methoxyl)-estradiol 3-methyl ether to the man. There was no evidence (by reverse isotope dilution) for 1-hydroxyestrone, 1-hydroxyestrone 3-methyl ether, 4-hydroxyestrone 3-methyl ether or 4-hydroxyestradiol 3-methyl ether as urinary metabolites of estradiol 3-methyl ether.", "contents": "Metabolism of radioactive 17 beta-estradiol 3-methyl ether by humans. A mixture of 2-3H and 4-14C-17beta-estradiol 3-methyl ether was administered orally to a man and to a woman. 34 and 35 percent of the 3H was liberated into the body water of the man and of the woman, respectively, reflecting reactions involving position 2. The metabolism of estradiol methyl ether was qualitatively similar to that observed previously for radioactive estradiol administered intravenously to the same subjects, as judged by the measurement of various urinary metabolites by reverse isotope dilution. Evidence was obtained for hydroxylation at position 2 without demethylation by the isolation of urinary 2-hydroxyestrone 3-methyl ether which retained 33% of the original 3H. This 3H was presumably at position 1, resulted from an NIH shift which does not occur during hydroxylation of estrone or estradiol. This was confirmed by subsequent administration of a mixture of 4-14C and 3H-(methoxyl)-estradiol 3-methyl ether to the man. There was no evidence (by reverse isotope dilution) for 1-hydroxyestrone, 1-hydroxyestrone 3-methyl ether, 4-hydroxyestrone 3-methyl ether or 4-hydroxyestradiol 3-methyl ether as urinary metabolites of estradiol 3-methyl ether."} {"id": "PMID:1265792", "title": "Androgen metabolism by rat epididymis. 3. Effect of castration and anti-androgens.", "content": "The in vivo and in vitro metabolism of 3H-testosterone by rat epididymis and the changes in epididymal weight have been studied after castration and treatment with anti-androgens. The utilization of 3H-testosterone was greatly reduced after castration as was the formation of 5alpha-reduced 17 beta-hydroxy metabolites. The formation of the 17 -keto metabolites was unaffected. Castration had no effect on the ratio between water and ether soluble radioactivity. Administration of testosterone propionate, necessary for giving normal stimulated prostate weight (150 mug/day), restored the metabolism of testosterone to approximately normal values. Estradiol benzoate and progesterone inhibited metabolism of testosterone in vitro and greatly reduced the formation of DHT (17 beta-hydroxy-5alpha-androstan-3-one) and 3 alpha-diol(5 alpha-androstane-3 alpha-17 beta-diol) by experiments both in vivo and in vitro. No effect of cyproterone acetate could be demonstrated on either the in vitro or in vivo metabolism of testosterone. Castration for 14 days reduced the epididymal weight to about 30% of that found in intact animals. Administration of testosterone propionate restored the epididymal weight to about 80% of normal. Estradiol benzoate and cyproterone acetate given to intact rats led to a decrease in the epididymal weight. Progesterone had no such effect. In 14 days castrated rats receiving testosterone propionate all three anti-androgens reduced the weight of the epididymis. In conclusion, our results show that the metabolic conversion of testosterone in epididymis to DHT and 3 alpha-diol is dramatically dependent on the hormonal status of the animal; castration or treatment with anti-androgens causes a reduced formation of the \"active\" androgens whilst testosterone replacement treatment restores the metabolism of testosterone to normal.", "contents": "Androgen metabolism by rat epididymis. 3. Effect of castration and anti-androgens. The in vivo and in vitro metabolism of 3H-testosterone by rat epididymis and the changes in epididymal weight have been studied after castration and treatment with anti-androgens. The utilization of 3H-testosterone was greatly reduced after castration as was the formation of 5alpha-reduced 17 beta-hydroxy metabolites. The formation of the 17 -keto metabolites was unaffected. Castration had no effect on the ratio between water and ether soluble radioactivity. Administration of testosterone propionate, necessary for giving normal stimulated prostate weight (150 mug/day), restored the metabolism of testosterone to approximately normal values. Estradiol benzoate and progesterone inhibited metabolism of testosterone in vitro and greatly reduced the formation of DHT (17 beta-hydroxy-5alpha-androstan-3-one) and 3 alpha-diol(5 alpha-androstane-3 alpha-17 beta-diol) by experiments both in vivo and in vitro. No effect of cyproterone acetate could be demonstrated on either the in vitro or in vivo metabolism of testosterone. Castration for 14 days reduced the epididymal weight to about 30% of that found in intact animals. Administration of testosterone propionate restored the epididymal weight to about 80% of normal. Estradiol benzoate and cyproterone acetate given to intact rats led to a decrease in the epididymal weight. Progesterone had no such effect. In 14 days castrated rats receiving testosterone propionate all three anti-androgens reduced the weight of the epididymis. In conclusion, our results show that the metabolic conversion of testosterone in epididymis to DHT and 3 alpha-diol is dramatically dependent on the hormonal status of the animal; castration or treatment with anti-androgens causes a reduced formation of the \"active\" androgens whilst testosterone replacement treatment restores the metabolism of testosterone to normal."} {"id": "PMID:1265793", "title": "The effect of a synthetic steroid (trienbolone) on the rate of release and excretion of subcutaneously administered estradiol in calves (18).", "content": "With the objective of obtaining values for the rate of release and excretion of subcutaneously implanted estradiol and to relate them to the metabolic effect of the hormone, a study was carried out with young Jersey bull calves. After subcutaneous administration of lactose tablets (implants) containing tritiated estradiol (4 mCi in 20 mg estradiol) the activity was followed in plasma, urine and feces for 107 days. Three calves received implants containing 140 mg trienbolone in addition to the 20 mg estradiol. In the first group maximum plasma concentration of estradiol-17 beta was 3 nmol/1. In the other group it was only 0.33 nmol/1. In calves receiving estradiol as the only steroid, 95% of the activity was excreted within 20 days after implantation. In the other group collection of urine and feces had to be carried out for 107 days in order to account for all the implanted activity. No 3H could be detected in urine and feces samples collected from the estradiol group more than 31 days ater implantation. The feces and urine samples collected from calves in the estradiol-trienbolone group 107 days after implantation contained from 1.4 - 3 nCi per gram. The remarkably decreasing effect of trienbolone on the release of estradiol and its possible importance for the effect of subcutaneously administered estradiol are discussed.", "contents": "The effect of a synthetic steroid (trienbolone) on the rate of release and excretion of subcutaneously administered estradiol in calves (18). With the objective of obtaining values for the rate of release and excretion of subcutaneously implanted estradiol and to relate them to the metabolic effect of the hormone, a study was carried out with young Jersey bull calves. After subcutaneous administration of lactose tablets (implants) containing tritiated estradiol (4 mCi in 20 mg estradiol) the activity was followed in plasma, urine and feces for 107 days. Three calves received implants containing 140 mg trienbolone in addition to the 20 mg estradiol. In the first group maximum plasma concentration of estradiol-17 beta was 3 nmol/1. In the other group it was only 0.33 nmol/1. In calves receiving estradiol as the only steroid, 95% of the activity was excreted within 20 days after implantation. In the other group collection of urine and feces had to be carried out for 107 days in order to account for all the implanted activity. No 3H could be detected in urine and feces samples collected from the estradiol group more than 31 days ater implantation. The feces and urine samples collected from calves in the estradiol-trienbolone group 107 days after implantation contained from 1.4 - 3 nCi per gram. The remarkably decreasing effect of trienbolone on the release of estradiol and its possible importance for the effect of subcutaneously administered estradiol are discussed."} {"id": "PMID:1265794", "title": "Saturated metabolites of progesterone in human myometrium during pregnancy.", "content": "A method for the separation and quantitative determination of epimeric 3alpha/beta-hydroxy-5alpha/beta-pregnan-20-ones by gas liquid chromatography and electron capture detection is presented. Reliability of the method and applicability to biological material was tested. In one total human uterus and 20 samples of myometrium the concentration of epimeric pregnanol-ones was determined. 3beta-hydroxy-5alpha-pregnan-20-one and 3alpha-hydroxy-5alpha-pregnan-20-one were present in similar quantitative range as progesterone and 20alpha-hydroxy-4-pregnen-3-one. A correlation between progesterone and concentration of metabolites could not be established. 3beta-hydroxy-5beta-pregnan-20-one was not detected in the tissue.", "contents": "Saturated metabolites of progesterone in human myometrium during pregnancy. A method for the separation and quantitative determination of epimeric 3alpha/beta-hydroxy-5alpha/beta-pregnan-20-ones by gas liquid chromatography and electron capture detection is presented. Reliability of the method and applicability to biological material was tested. In one total human uterus and 20 samples of myometrium the concentration of epimeric pregnanol-ones was determined. 3beta-hydroxy-5alpha-pregnan-20-one and 3alpha-hydroxy-5alpha-pregnan-20-one were present in similar quantitative range as progesterone and 20alpha-hydroxy-4-pregnen-3-one. A correlation between progesterone and concentration of metabolites could not be established. 3beta-hydroxy-5beta-pregnan-20-one was not detected in the tissue."} {"id": "PMID:1265795", "title": "In vitro inhibition of rat liver cholest-5en-3 beta-ol (cholesterol) biosynthesis by non-mercurial sulfhydryl reagents.", "content": "In vitro conversion of 2-14C-mevalonate to cholest-5en-3 beta-ol (cholesterol) in rat liver homogenates is inhibited by arsenite, beta-mercaptoethanol, dithiothreitol and ethanethiol. Two sterols containing 20 carbon atoms accumulate under these conditions. One of these is identified as 4,4 dimethyl-5alpha-cholest-8en-3beta-ol and the other tentatively identified as 4,4 dimethyl-5alpha-cholest-8,24-dien-3beta-ol. Based on these observations, these non-mercurial sulfhydryl reagents do not inhibit 5alpha-lanosta-8,24-dien-3beta-ol 14alpha demethylase.", "contents": "In vitro inhibition of rat liver cholest-5en-3 beta-ol (cholesterol) biosynthesis by non-mercurial sulfhydryl reagents. In vitro conversion of 2-14C-mevalonate to cholest-5en-3 beta-ol (cholesterol) in rat liver homogenates is inhibited by arsenite, beta-mercaptoethanol, dithiothreitol and ethanethiol. Two sterols containing 20 carbon atoms accumulate under these conditions. One of these is identified as 4,4 dimethyl-5alpha-cholest-8en-3beta-ol and the other tentatively identified as 4,4 dimethyl-5alpha-cholest-8,24-dien-3beta-ol. Based on these observations, these non-mercurial sulfhydryl reagents do not inhibit 5alpha-lanosta-8,24-dien-3beta-ol 14alpha demethylase."} {"id": "PMID:1265796", "title": "The in vitro synthesis and secretion of alpha-ecdysone by the ring glands of the fly, Sarcophaga bullata.", "content": "The in vitro secretory product of larval Sarcophage bullata ring glands has been identified as 2beta, 3beta, 14alpha, 22R, 25-pentahydroxy-5beta-cholest-7-en-6-one (alpha-ecdysone). Mid to late 3rd instar larval ecdysones were isolated and identified as 2beta, 3beta, 14alpha, 20R, 22R, 25-hexahydroxy-5beta-cholest-7-en-6-one (beta-ecdysone) and alpha-ecdysone at a ratio of 27:1. The low level of alpha-ecdysone in vivo, relative to its exclusive in vitro synthesis and secretion by the ring glands, is a function of the very active C20 hydroxylation mechanism in tissues peripheral to the ring gland. The role of alpha-ecdysone as a prohormone in dipteran metamorphosis is discussed.", "contents": "The in vitro synthesis and secretion of alpha-ecdysone by the ring glands of the fly, Sarcophaga bullata. The in vitro secretory product of larval Sarcophage bullata ring glands has been identified as 2beta, 3beta, 14alpha, 22R, 25-pentahydroxy-5beta-cholest-7-en-6-one (alpha-ecdysone). Mid to late 3rd instar larval ecdysones were isolated and identified as 2beta, 3beta, 14alpha, 20R, 22R, 25-hexahydroxy-5beta-cholest-7-en-6-one (beta-ecdysone) and alpha-ecdysone at a ratio of 27:1. The low level of alpha-ecdysone in vivo, relative to its exclusive in vitro synthesis and secretion by the ring glands, is a function of the very active C20 hydroxylation mechanism in tissues peripheral to the ring gland. The role of alpha-ecdysone as a prohormone in dipteran metamorphosis is discussed."} {"id": "PMID:1265797", "title": "Synthesis of steroidal cyclophosphamides.", "content": "The Reformatsky product of estrone methyl ether and ethyl bromo-acetate was transformed by two separate routes to 21-amino-3-methoxy-17alpha-pregna-1,3,5(10)-trien-17beta-ol (9). Cyclization with bis- (2-chloroethyl) phosphoramide dichloride produced the steroidal cyclophosphamide 10. Analogous syntheses transformed androstenolone into steroidal cyclophosphamide 20 and androstenedione into steroidal cyclophosphamide 28.", "contents": "Synthesis of steroidal cyclophosphamides. The Reformatsky product of estrone methyl ether and ethyl bromo-acetate was transformed by two separate routes to 21-amino-3-methoxy-17alpha-pregna-1,3,5(10)-trien-17beta-ol (9). Cyclization with bis- (2-chloroethyl) phosphoramide dichloride produced the steroidal cyclophosphamide 10. Analogous syntheses transformed androstenolone into steroidal cyclophosphamide 20 and androstenedione into steroidal cyclophosphamide 28."} {"id": "PMID:1265798", "title": "Inhibition of the conversion of cholesterol to pregnenolone in bovine adrenocortical preparations.", "content": "The inhibition of the conversion of [4-14C] cholesterol to [4-14C] pregnenolone by a number of steroids has been studied in bovine adrenocortical mitochondrial acetonedried preparations. At equimolar substrate and inhibitor concentrations (3.3 muM) the most potent inhibitors were cholesterol derivatives containing a nitrogen function at c-22, followed by derivatives containing oxygen functions at c-22 or c-20 or both. The presence of a hydroxyl group at c-17 or the replacement of the 3beta-hydroxyl group by fluorine reduced the inhibitory efficacy. In the presence of inhibitors that were also relatively good substrates of the cholesterol side-chain cleavage system, such as some cholesterol derivatives hydroxylated in the side-chain,the rate of [4-14C] pregnenolone formation increased with time as the inhibitor was consumed. (20S)-20,21-Dihydroxycholesterol exerted such an effect on the kinetics of [4-14C]pregnenolone formation, and yielded 21-hydroxypregnenolone which was identified by gas chromatography-mass spectrometry. The synthesis of (20R)-22-ketocholesterol, of (20R,22R)-22hydroxycholesterol, (20R,22S)-hydroxycholesterol, and of (20S)-desmosterol is described.", "contents": "Inhibition of the conversion of cholesterol to pregnenolone in bovine adrenocortical preparations. The inhibition of the conversion of [4-14C] cholesterol to [4-14C] pregnenolone by a number of steroids has been studied in bovine adrenocortical mitochondrial acetonedried preparations. At equimolar substrate and inhibitor concentrations (3.3 muM) the most potent inhibitors were cholesterol derivatives containing a nitrogen function at c-22, followed by derivatives containing oxygen functions at c-22 or c-20 or both. The presence of a hydroxyl group at c-17 or the replacement of the 3beta-hydroxyl group by fluorine reduced the inhibitory efficacy. In the presence of inhibitors that were also relatively good substrates of the cholesterol side-chain cleavage system, such as some cholesterol derivatives hydroxylated in the side-chain,the rate of [4-14C] pregnenolone formation increased with time as the inhibitor was consumed. (20S)-20,21-Dihydroxycholesterol exerted such an effect on the kinetics of [4-14C]pregnenolone formation, and yielded 21-hydroxypregnenolone which was identified by gas chromatography-mass spectrometry. The synthesis of (20R)-22-ketocholesterol, of (20R,22R)-22hydroxycholesterol, (20R,22S)-hydroxycholesterol, and of (20S)-desmosterol is described."} {"id": "PMID:1265799", "title": "New bile alcohols - synthesis of (22R)- and (22S)-5beta-cholestane-3alpha,7alpha,12alpha,22,25-pentols.", "content": "The synthesis of (22R)- and (22S)-5beta-cholestane-3alpha,7alpha,12alpha,22,25-pentols is described. Bisnorcholyl aldehyde was prepared from cholic acid and converted into the cholestane-pentols by a Grignard reaction with 3-methyl-3-(tetrahydropyran-2-yloxy)-butynylmagnesium bromide followed by hydrogenation and acid hydrolysis. One of the synthetic pentols, the 22R-isomer was identical with a metabolite of 5beta-cholestane-3alpha,7alpha,25-triol formed in the rabbit.", "contents": "New bile alcohols - synthesis of (22R)- and (22S)-5beta-cholestane-3alpha,7alpha,12alpha,22,25-pentols. The synthesis of (22R)- and (22S)-5beta-cholestane-3alpha,7alpha,12alpha,22,25-pentols is described. Bisnorcholyl aldehyde was prepared from cholic acid and converted into the cholestane-pentols by a Grignard reaction with 3-methyl-3-(tetrahydropyran-2-yloxy)-butynylmagnesium bromide followed by hydrogenation and acid hydrolysis. One of the synthetic pentols, the 22R-isomer was identical with a metabolite of 5beta-cholestane-3alpha,7alpha,25-triol formed in the rabbit."} {"id": "PMID:1265800", "title": "Induction of vaginal mucification in rats with testosterone and 17beta-hydroxy-5alpha-androstan-3-one.", "content": "Based on histological criteria, Kingsley and Bogdanove (3) reported that the benzoate ester of 17beta-hydroxy-5alpha-androstan-3-one (5alpha-DHT), unlike testosterone propionate, is unable to induce vaginal mucification when given subcutaneously to rats. In contrats, Kennedy (4) found in estrogen-pretreated rats that both 5alpha-DHT and testosterone induced vaginal mucification as indicated by increased vaginal sialic acid concentration. To determine if esterification of these androgens altered their ability to induce vaginal mucification, ovariectomized rats, pretreated for 3 days with 0.25 mug estradiol-17beta, were treated for 8 days with either sesame oil or 7 mumoles of testosterone, 5alpha-DHT and their respective propionate and benzoate esters. All treatments except 5-alpha-DHT benzoate increased vaginal weight and vaginal mucification, as assessed histochemically and biochemically. 5alpha-DHT propionate was less effective than 5alpha-DHT while testosterone benzoate, but not propionate was less effective than testosterone. To determine if estrogens are necessary for the vaginal effects of androgens, ovariectomized and ovariectomized-adrenalectomized rats were treated with testosterone or 5alpha-DHT. Adrenalectomy did not significantly affect the vaginal response to either androgen. It is therefore concluded that androgens are capable of inducing vaginal mucification in the absence of estrogens.", "contents": "Induction of vaginal mucification in rats with testosterone and 17beta-hydroxy-5alpha-androstan-3-one. Based on histological criteria, Kingsley and Bogdanove (3) reported that the benzoate ester of 17beta-hydroxy-5alpha-androstan-3-one (5alpha-DHT), unlike testosterone propionate, is unable to induce vaginal mucification when given subcutaneously to rats. In contrats, Kennedy (4) found in estrogen-pretreated rats that both 5alpha-DHT and testosterone induced vaginal mucification as indicated by increased vaginal sialic acid concentration. To determine if esterification of these androgens altered their ability to induce vaginal mucification, ovariectomized rats, pretreated for 3 days with 0.25 mug estradiol-17beta, were treated for 8 days with either sesame oil or 7 mumoles of testosterone, 5alpha-DHT and their respective propionate and benzoate esters. All treatments except 5-alpha-DHT benzoate increased vaginal weight and vaginal mucification, as assessed histochemically and biochemically. 5alpha-DHT propionate was less effective than 5alpha-DHT while testosterone benzoate, but not propionate was less effective than testosterone. To determine if estrogens are necessary for the vaginal effects of androgens, ovariectomized and ovariectomized-adrenalectomized rats were treated with testosterone or 5alpha-DHT. Adrenalectomy did not significantly affect the vaginal response to either androgen. It is therefore concluded that androgens are capable of inducing vaginal mucification in the absence of estrogens."} {"id": "PMID:1265803", "title": "Hypertension as an important factor for cerebrovascular atherogenesis in rats.", "content": "A new model for studies on atherogenesis in the cerebrovascular system was obtained by using recently established stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP on a hypercholesterolemic diet (20% suet, 5% cholesterol, and 2% cholic acid) had ring-like fat deposits in the circle of Willis, which were detected within a few weeks by new techniques for the macroscopical demonstration of fat deposits \"as a whole\" and were proved to be good quantitative indices for the initiation of atherogenesis. Experimental studies using more than 200 rats including SHRSP, experimental hypertensive rats (renal infarction hypertension) and WK rats, fed a hypercholesterolemic diet with 1% salt in the drinking water for 1 week, 2 weeks, 10 weeks and more than 10 weeks, revealed that the arterial fat deposition in the brain was affected by BP, serum cholesterol level, strain difference and age. High BP was confirmed to be more important than the other factors by the quantitative analysis of sudanophilic rings in relation to BP.", "contents": "Hypertension as an important factor for cerebrovascular atherogenesis in rats. A new model for studies on atherogenesis in the cerebrovascular system was obtained by using recently established stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP on a hypercholesterolemic diet (20% suet, 5% cholesterol, and 2% cholic acid) had ring-like fat deposits in the circle of Willis, which were detected within a few weeks by new techniques for the macroscopical demonstration of fat deposits \"as a whole\" and were proved to be good quantitative indices for the initiation of atherogenesis. Experimental studies using more than 200 rats including SHRSP, experimental hypertensive rats (renal infarction hypertension) and WK rats, fed a hypercholesterolemic diet with 1% salt in the drinking water for 1 week, 2 weeks, 10 weeks and more than 10 weeks, revealed that the arterial fat deposition in the brain was affected by BP, serum cholesterol level, strain difference and age. High BP was confirmed to be more important than the other factors by the quantitative analysis of sudanophilic rings in relation to BP."} {"id": "PMID:1265802", "title": "Comparison of computerized tomography and radionuclide imaging in \"stroke\".", "content": "Forty patients were studied by computerized tomography and by radionuclide brain imaging. The final diagnosis was infarction in 29 patients, intracerebral hematoma in seven, acute SAH in one, and old cerebrovascular accidents in three. CT was far superior to RN in detecting intracerebral hematomas and distinguishing them from cerebral infarction. The results of CT and RN tests were comparable regarding the percentage of abnormalities. However, the results in the same patients were not identical in 55% of the cases, indicating a complementary role for the two tests. There was no relationship between the frequency of abnormalities on CT and the time lapse after the onset of cerebral infarction. RN uptake was not seen in patients with old cerebrovascular accidents.", "contents": "Comparison of computerized tomography and radionuclide imaging in \"stroke\". Forty patients were studied by computerized tomography and by radionuclide brain imaging. The final diagnosis was infarction in 29 patients, intracerebral hematoma in seven, acute SAH in one, and old cerebrovascular accidents in three. CT was far superior to RN in detecting intracerebral hematomas and distinguishing them from cerebral infarction. The results of CT and RN tests were comparable regarding the percentage of abnormalities. However, the results in the same patients were not identical in 55% of the cases, indicating a complementary role for the two tests. There was no relationship between the frequency of abnormalities on CT and the time lapse after the onset of cerebral infarction. RN uptake was not seen in patients with old cerebrovascular accidents."} {"id": "PMID:1265804", "title": "Heterogeneities of regional cerebral blood flow during hypoxia-ischemia in the rat.", "content": "The distribution of regional cerebral blood flow (rCBF) within the cerebral hemispheres of rats was investigated following an hypoxic-ischemic insult consisting of a 30-minute exposure to 6.5% to 7% inspired oxygen coupled with unilateral ligation of the common carotid artery and maintenance of normal blood pressure (modified Levine preparation). rCBF was estimated by means of an autoradiographic method employing 14C-antipyrine. Mean arterial PO2 values of 26.8 to 27.5 mm Hg were attained during the insult period. rCBF rose above control values in all structures of the hemisphere contralateral to carotid artery ligation. Structures of the hemisphere ipsilateral to arterial ligation exhibited rCBF values less than those of the opposite side. However, the degree to which carotid artery occlusion reduced the rCBF of a structure relative to that of the opposite hemisphere varied greatly from region to region, with the greatest decrements occurring in the lateral cerebral cortex and the caudoputamen. Previous studies in this model have shown that these regions of the hemisphere ipsilateral to carotid artery occlusion are zones of frequent histological injury. These data suggest that inhomogeneities of rCBF may in part determine the phenomenon of \"selective vulnerability\" of the nervous system to hypoxia-ischemia.", "contents": "Heterogeneities of regional cerebral blood flow during hypoxia-ischemia in the rat. The distribution of regional cerebral blood flow (rCBF) within the cerebral hemispheres of rats was investigated following an hypoxic-ischemic insult consisting of a 30-minute exposure to 6.5% to 7% inspired oxygen coupled with unilateral ligation of the common carotid artery and maintenance of normal blood pressure (modified Levine preparation). rCBF was estimated by means of an autoradiographic method employing 14C-antipyrine. Mean arterial PO2 values of 26.8 to 27.5 mm Hg were attained during the insult period. rCBF rose above control values in all structures of the hemisphere contralateral to carotid artery ligation. Structures of the hemisphere ipsilateral to arterial ligation exhibited rCBF values less than those of the opposite side. However, the degree to which carotid artery occlusion reduced the rCBF of a structure relative to that of the opposite hemisphere varied greatly from region to region, with the greatest decrements occurring in the lateral cerebral cortex and the caudoputamen. Previous studies in this model have shown that these regions of the hemisphere ipsilateral to carotid artery occlusion are zones of frequent histological injury. These data suggest that inhomogeneities of rCBF may in part determine the phenomenon of \"selective vulnerability\" of the nervous system to hypoxia-ischemia."} {"id": "PMID:1265805", "title": "A pilot study of urokinase therapy in cerebral infarction.", "content": "Thirty-one patients with acute cerebral infarction were treated with the thrombolytic agent urokinase for either a single or a double infusion period, each of ten hours. The effects of urokinase therapy administered at dosage rates of 1,200, 1,500 or 1,700 CTA urokinase units per pound of body weight per hour were followed by serial blood coagulation and other biochemical studies. In the dosage used, urokinase produced a prompt sustained increase, 20-fold to 40-fold, of plasma thrombolytic activity with relatively minor disturbance of the blood coagulation system. Nevertheless, hemorrhagic complications occurred in several patients and distinctly favorable therapeutic effects were not observed.", "contents": "A pilot study of urokinase therapy in cerebral infarction. Thirty-one patients with acute cerebral infarction were treated with the thrombolytic agent urokinase for either a single or a double infusion period, each of ten hours. The effects of urokinase therapy administered at dosage rates of 1,200, 1,500 or 1,700 CTA urokinase units per pound of body weight per hour were followed by serial blood coagulation and other biochemical studies. In the dosage used, urokinase produced a prompt sustained increase, 20-fold to 40-fold, of plasma thrombolytic activity with relatively minor disturbance of the blood coagulation system. Nevertheless, hemorrhagic complications occurred in several patients and distinctly favorable therapeutic effects were not observed."} {"id": "PMID:1265806", "title": "Intracranial bleeding associated with urokinase therapy for acute ischemic hemispheral stroke.", "content": "Four patients undergoing urokinase infusion therapy for acute occlusive cerebrovascular disease had intracerebral hemorrhage in the ischemic hemisphere. Three patients died during the acute phase of their illness and an autopsy was performed on two. The pathogenesis of cerebral bleeding in these case reports is discussed.", "contents": "Intracranial bleeding associated with urokinase therapy for acute ischemic hemispheral stroke. Four patients undergoing urokinase infusion therapy for acute occlusive cerebrovascular disease had intracerebral hemorrhage in the ischemic hemisphere. Three patients died during the acute phase of their illness and an autopsy was performed on two. The pathogenesis of cerebral bleeding in these case reports is discussed."} {"id": "PMID:1265813", "title": "Self-destructive consequences of sex-role socialization.", "content": "Suicide proneness and self-destruction scales, together with measures of self-favorability and self-confidence, were administered to two samples (n = 106 and n = 213). The affective responses of the second sample (134 women and 79 men) were measured by asking respondents to circle adjectives classified for activity-passivity, positive-negativeness, and extroversion-introversion that expressed their feelings toward eight situations. Women scored lower than men on suicide proneness, higher on self-destruction, and lower on self-favorability and self-confidence. Women reacted more passively to the situations than men and more negatively to the public challenge situation. Women tend to extrovert (turn outward on others) their positive feelings in pleasant situations and to introvert (turn blame on themselves) their negative reactions to unpleasant situations. Men do the reverse. It is suggested that women are self-destructive in passive ways, reflecting their lack of self-favorability and confidence and manifested by failure to react to everyday situations in ego-building ways.", "contents": "Self-destructive consequences of sex-role socialization. Suicide proneness and self-destruction scales, together with measures of self-favorability and self-confidence, were administered to two samples (n = 106 and n = 213). The affective responses of the second sample (134 women and 79 men) were measured by asking respondents to circle adjectives classified for activity-passivity, positive-negativeness, and extroversion-introversion that expressed their feelings toward eight situations. Women scored lower than men on suicide proneness, higher on self-destruction, and lower on self-favorability and self-confidence. Women reacted more passively to the situations than men and more negatively to the public challenge situation. Women tend to extrovert (turn outward on others) their positive feelings in pleasant situations and to introvert (turn blame on themselves) their negative reactions to unpleasant situations. Men do the reverse. It is suggested that women are self-destructive in passive ways, reflecting their lack of self-favorability and confidence and manifested by failure to react to everyday situations in ego-building ways."} {"id": "PMID:1265814", "title": "Self-attitudes and suicidal behavior.", "content": "Findings are reported concerning the hypothesized relationship between adoption of suicidal responses (ideation, threats, attempts) and antecedent negative self-attitudes. Data were provided by junior high school student (N = 3,148) responses to questionnaires administered three times at annual intervals. Antecedent negative self-attitudes were measured by a seven-item self-derogation scale at the first testing. Adoption of suicidal responses was indicated by earlier denial and subsequent affirmation of the response (self-reports). Findings indicate that suicidal behaviors are responses (whether or not subsequently continued) to experiences of negative self-attitudes in the more recent past. However, whether or not suicidal behaviors are related to self-derogating feelings in the more remote past can be seen as a function of a sex-social-class-mode of suicidal response interaction.", "contents": "Self-attitudes and suicidal behavior. Findings are reported concerning the hypothesized relationship between adoption of suicidal responses (ideation, threats, attempts) and antecedent negative self-attitudes. Data were provided by junior high school student (N = 3,148) responses to questionnaires administered three times at annual intervals. Antecedent negative self-attitudes were measured by a seven-item self-derogation scale at the first testing. Adoption of suicidal responses was indicated by earlier denial and subsequent affirmation of the response (self-reports). Findings indicate that suicidal behaviors are responses (whether or not subsequently continued) to experiences of negative self-attitudes in the more recent past. However, whether or not suicidal behaviors are related to self-derogating feelings in the more remote past can be seen as a function of a sex-social-class-mode of suicidal response interaction."} {"id": "PMID:1265808", "title": "Recovery of the cortical evoked response following temporary middle cerebral artery occlusion in baboons: relation to local blood flow and PO2.", "content": "The degree of recovery of the somatosensory cortical evoked response following a period (15 to 65 minutes) of partial ischemia, produced by temporary occlusion of the middle cerebral artery (MCA), was assessed in baboons and related to the local tissue blood flow and PO2 before, during and after the occlusion. Flow was measured using the technique of two-minute hydrogen clearance. Failure of complete recovery of the evoked response was associated with significantly greater depths of ischemia and tissue hypoxia during occlusion, and with significantly greater and persisting tissue hypoxia after occlusion, than complete recovery. Complete recovery of the evoked response also was associated with tissue hyperoxia after occlusion. The reduced postocclusive PO2 levels associated with incomplete recovery of the evoked response suggest that reduced perfusion during ischemia was sufficiently severe to cause some degree of irreversible anoxic damage. The effect of a brief (three to ten minutes) period of ventilation with air (instead of oxygen) under such low-flow conditions was to depress the evoked response significantly further; normally perfused brain, however, was unaffected by this procedure. This finding has clinical implications in regard to normobaric oxygen therapy.", "contents": "Recovery of the cortical evoked response following temporary middle cerebral artery occlusion in baboons: relation to local blood flow and PO2. The degree of recovery of the somatosensory cortical evoked response following a period (15 to 65 minutes) of partial ischemia, produced by temporary occlusion of the middle cerebral artery (MCA), was assessed in baboons and related to the local tissue blood flow and PO2 before, during and after the occlusion. Flow was measured using the technique of two-minute hydrogen clearance. Failure of complete recovery of the evoked response was associated with significantly greater depths of ischemia and tissue hypoxia during occlusion, and with significantly greater and persisting tissue hypoxia after occlusion, than complete recovery. Complete recovery of the evoked response also was associated with tissue hyperoxia after occlusion. The reduced postocclusive PO2 levels associated with incomplete recovery of the evoked response suggest that reduced perfusion during ischemia was sufficiently severe to cause some degree of irreversible anoxic damage. The effect of a brief (three to ten minutes) period of ventilation with air (instead of oxygen) under such low-flow conditions was to depress the evoked response significantly further; normally perfused brain, however, was unaffected by this procedure. This finding has clinical implications in regard to normobaric oxygen therapy."} {"id": "PMID:1265807", "title": "Cerebral blood flow regulation: vascular resistance adjustments in the circle of Willis.", "content": "Continuous measurements of systemic blood pressure (BP), cerebral perfusion pressure and CBF were accomplished in the cat during transient hypertension, hypercapnia and bilateral carotid artery occlusion. From these measurements resistance values in the circle of Willis and in the cerebral arteries distal to the circle were calculated. The results indicate that the arteries of the circle of Willis and the arteries distal to the circle of Willis dilate and contract independently.", "contents": "Cerebral blood flow regulation: vascular resistance adjustments in the circle of Willis. Continuous measurements of systemic blood pressure (BP), cerebral perfusion pressure and CBF were accomplished in the cat during transient hypertension, hypercapnia and bilateral carotid artery occlusion. From these measurements resistance values in the circle of Willis and in the cerebral arteries distal to the circle were calculated. The results indicate that the arteries of the circle of Willis and the arteries distal to the circle of Willis dilate and contract independently."} {"id": "PMID:1265815", "title": "A psychological autopsy of an indian adolescent suicide with implications for community services.", "content": "This psychological autopsy of the suicidal death of an adolescent Indian boy includes a brief family background, a history of his difficulties, and a report of his psychological evaluation. There is an attempt to understand the societal and familial factors that seem to have prediposed him to commit suicide. The report includes an analysis of the resources currently available in Indian communities and a recommendation for the kinds of resources that might prevent suicide in this setting.", "contents": "A psychological autopsy of an indian adolescent suicide with implications for community services. This psychological autopsy of the suicidal death of an adolescent Indian boy includes a brief family background, a history of his difficulties, and a report of his psychological evaluation. There is an attempt to understand the societal and familial factors that seem to have prediposed him to commit suicide. The report includes an analysis of the resources currently available in Indian communities and a recommendation for the kinds of resources that might prevent suicide in this setting."} {"id": "PMID:1265809", "title": "Aphasia in acute stroke.", "content": "Previous surveys of stroke populations have offered only cursory information on language disturbance, and, conversely, few surveys of aphasic populations have dealth exclusively with stroke or with acute phenomena. This paper describes aphasia in 850 acute stroke patients consecutively registered by the Harlem Regional Stroke Program, of whom 177 (21%) were aphasic; of these, nine were of Broca's type, 24 were of Wernicke's type, 14 were of anomic, ten were conduction, seven were of \"isolation\" type, and 107 were \"mixed.\" An unexpected finding was a significant over-representation of men among the nonfluent aphasics. During the following four to 12 weeks, 12% of fluent aphasics died, and 12% remained moderately or severely impaired; among survivors, aphasia improved in 74%, and in 44% it cleared completely. During the same period, 32% of nonfluent aphasics died, and 34% remained moderately or severely impaired; among survivors, aphasia improved in 52%, and in only 13% did it clear completely. In both fluent and nonfluent groups, hemiparesis and/or visual field cut were associated with poor prognosis.", "contents": "Aphasia in acute stroke. Previous surveys of stroke populations have offered only cursory information on language disturbance, and, conversely, few surveys of aphasic populations have dealth exclusively with stroke or with acute phenomena. This paper describes aphasia in 850 acute stroke patients consecutively registered by the Harlem Regional Stroke Program, of whom 177 (21%) were aphasic; of these, nine were of Broca's type, 24 were of Wernicke's type, 14 were of anomic, ten were conduction, seven were of \"isolation\" type, and 107 were \"mixed.\" An unexpected finding was a significant over-representation of men among the nonfluent aphasics. During the following four to 12 weeks, 12% of fluent aphasics died, and 12% remained moderately or severely impaired; among survivors, aphasia improved in 74%, and in 44% it cleared completely. During the same period, 32% of nonfluent aphasics died, and 34% remained moderately or severely impaired; among survivors, aphasia improved in 52%, and in only 13% did it clear completely. In both fluent and nonfluent groups, hemiparesis and/or visual field cut were associated with poor prognosis."} {"id": "PMID:1265810", "title": "An in vitro study of prolonged vasospasm of a rabbit cerebral artery.", "content": "Longitudinal stretch of the rabbit basilar artery produces local injury followed by prolonged circular constriction. After stretching and rapid release in vitro localized constrictions promptly occurred. This could be prevented by prior treatment with cyanide or calcium-free solution. Once produced, constrictions persisted for more than 72 hours. Previously induced constriction was not reversed by treatment for two hours with cyanide or by removing calcium. Histological observation indicated that constricted areas were associated with a discrete circumferential rupture of the internal elastic lamina and disruption and thinning of the underlying media. Specific catecholamine fluorescence at the adventitio-medial junction was unchanged in constricted areas. The relationship between smooth muscle cell length and resting tension of artery segments with and without constrictions was compared. Segments with constrictions had a shorter muscle length for any given resting tension, which confirms that constriction was not due to passive collapse of the vessel wall. These findings suggest that injury of cerebrovascular smooth muscle may result in essentially irreversible vasoconstriction. Such a mechanism could contribute to the pathogenesis of prolonged cerebral vasospasm after SAH or traumatic injury to the cerebrum.", "contents": "An in vitro study of prolonged vasospasm of a rabbit cerebral artery. Longitudinal stretch of the rabbit basilar artery produces local injury followed by prolonged circular constriction. After stretching and rapid release in vitro localized constrictions promptly occurred. This could be prevented by prior treatment with cyanide or calcium-free solution. Once produced, constrictions persisted for more than 72 hours. Previously induced constriction was not reversed by treatment for two hours with cyanide or by removing calcium. Histological observation indicated that constricted areas were associated with a discrete circumferential rupture of the internal elastic lamina and disruption and thinning of the underlying media. Specific catecholamine fluorescence at the adventitio-medial junction was unchanged in constricted areas. The relationship between smooth muscle cell length and resting tension of artery segments with and without constrictions was compared. Segments with constrictions had a shorter muscle length for any given resting tension, which confirms that constriction was not due to passive collapse of the vessel wall. These findings suggest that injury of cerebrovascular smooth muscle may result in essentially irreversible vasoconstriction. Such a mechanism could contribute to the pathogenesis of prolonged cerebral vasospasm after SAH or traumatic injury to the cerebrum."} {"id": "PMID:1265816", "title": "Banality reinvestigated: A computer-based content analysis of suicidal and forced death documents.", "content": "Suicide and simulated notes and forced-death documents were processed on the Harvard III Psycho-Sociological Dictionary. For each text, frequencies of related words were generated; these were contrasted with each other and with baseline data using z scores. The results indicated that the suicidal groups were more \"deviant.\" Other findings are concreteness and constriction of focus for suicides--a pattern suggesting denial just prior to the deed. The forced-death group seemed to be more meaningfully in contact with life and aware of responsibility. The stimulated group appeared to be fabricating a popular stereotype rather than exhibiting empathy. Implications were discussed.", "contents": "Banality reinvestigated: A computer-based content analysis of suicidal and forced death documents. Suicide and simulated notes and forced-death documents were processed on the Harvard III Psycho-Sociological Dictionary. For each text, frequencies of related words were generated; these were contrasted with each other and with baseline data using z scores. The results indicated that the suicidal groups were more \"deviant.\" Other findings are concreteness and constriction of focus for suicides--a pattern suggesting denial just prior to the deed. The forced-death group seemed to be more meaningfully in contact with life and aware of responsibility. The stimulated group appeared to be fabricating a popular stereotype rather than exhibiting empathy. Implications were discussed."} {"id": "PMID:1265818", "title": "Some observations on filariasis in Western Samoa after mass administration of diethylcarbamazine.", "content": "An extremely efficient diethylcarbamazine administration campaign to eradicate Wuchereria bancrofti has been carried out in Western Samoa. The use of the membrane-filtration technique has shown that a large number of people exhibit extremely low microfilarial densities, often with less than 10 in 1 ml of venous blood. It was found that one of these low level microfilaria carriers readily infected the local vector Aedes polynesiensis and that development took place to the infective stage. It was estimated that 497 infective larvae of W. bancrofti will enter the human population of Western Samoa daily from these vectors. Resumption of filariasis transmission is possible and surveillance of the human and mosquito populations should be continued for a number of years and control measures taken quickly if further transmission occurs.", "contents": "Some observations on filariasis in Western Samoa after mass administration of diethylcarbamazine. An extremely efficient diethylcarbamazine administration campaign to eradicate Wuchereria bancrofti has been carried out in Western Samoa. The use of the membrane-filtration technique has shown that a large number of people exhibit extremely low microfilarial densities, often with less than 10 in 1 ml of venous blood. It was found that one of these low level microfilaria carriers readily infected the local vector Aedes polynesiensis and that development took place to the infective stage. It was estimated that 497 infective larvae of W. bancrofti will enter the human population of Western Samoa daily from these vectors. Resumption of filariasis transmission is possible and surveillance of the human and mosquito populations should be continued for a number of years and control measures taken quickly if further transmission occurs."} {"id": "PMID:1265819", "title": "Leptospirosis in Trinidad and Grenada, with special reference to the mongoose.", "content": "In Trinidad, six Leptospira isolates were made from 957 febrile patients between 1968 amd 1972. In addition, CF antibodies were detected in 6-6% of febrile patients and human survey sera collected during this period. In 1972 alone, 10-4% (38/363) of sera examined had CF titres consistent with positive exposure to the disease. Grenada does not report leptospirosis, but the disease is common in mongooses in both Trinidad and Grenada. Serogroups Icterohaemorrhagiae, Pomona and Canicola are present in Grenada with 35-2% of mongooses examined being seropositive. Five Canicola strains of Leptospira were isolated from mongooses in Trinidad and serological studies showed that this was the most common serogroup from mongooses on the island. A total of 31 strains recorded from at least seven different serogroups and eight named serotypes have been isolated from humans, rats and mongooses in Trinidad. Human leptospirosis is probably more common in the Caribbean than the medical records indicate.", "contents": "Leptospirosis in Trinidad and Grenada, with special reference to the mongoose. In Trinidad, six Leptospira isolates were made from 957 febrile patients between 1968 amd 1972. In addition, CF antibodies were detected in 6-6% of febrile patients and human survey sera collected during this period. In 1972 alone, 10-4% (38/363) of sera examined had CF titres consistent with positive exposure to the disease. Grenada does not report leptospirosis, but the disease is common in mongooses in both Trinidad and Grenada. Serogroups Icterohaemorrhagiae, Pomona and Canicola are present in Grenada with 35-2% of mongooses examined being seropositive. Five Canicola strains of Leptospira were isolated from mongooses in Trinidad and serological studies showed that this was the most common serogroup from mongooses on the island. A total of 31 strains recorded from at least seven different serogroups and eight named serotypes have been isolated from humans, rats and mongooses in Trinidad. Human leptospirosis is probably more common in the Caribbean than the medical records indicate."} {"id": "PMID:1265811", "title": "Epidemiology of cerebrovascular disease in Tartu, Estonia, USSR, 1970 through 1973.", "content": "This study was undertaken to establish the incidence and mortality for various types of cerebrovascular disease in the population of Tartu. All medical records for this population were reviewed for the period 1970 through 1973, and those with a diagnosis of brain infarction, transient ischemic attacks, cerebral hemorrhage or subarachnoid hemorrhage were identified. Only the first stroke was considered when determining incidence. A total of 786 cases were included in the study. Without cases of transient ischemic attacks, the number was 667 (e.g., cases of stroke). Cerebral infarction accounted for 80% of all strokes, cerebral hemorrhage for 13.5% and subarachnoid hemorrhage for 6.5%. The incidence rate for stroke was higher for men than for women and significantly increased in each older age group. The rate for all persons was 184 per 100,000 population per year. The incidence of transient ischemic attacks was 33 per 100,000 population per year. The mortality rate for stroke for this population was 98/100,000 per year. The data on incidence of stroke and its type, its dependence on age and sex, and mortality rate are close to the corresponding data reported from other countries.", "contents": "Epidemiology of cerebrovascular disease in Tartu, Estonia, USSR, 1970 through 1973. This study was undertaken to establish the incidence and mortality for various types of cerebrovascular disease in the population of Tartu. All medical records for this population were reviewed for the period 1970 through 1973, and those with a diagnosis of brain infarction, transient ischemic attacks, cerebral hemorrhage or subarachnoid hemorrhage were identified. Only the first stroke was considered when determining incidence. A total of 786 cases were included in the study. Without cases of transient ischemic attacks, the number was 667 (e.g., cases of stroke). Cerebral infarction accounted for 80% of all strokes, cerebral hemorrhage for 13.5% and subarachnoid hemorrhage for 6.5%. The incidence rate for stroke was higher for men than for women and significantly increased in each older age group. The rate for all persons was 184 per 100,000 population per year. The incidence of transient ischemic attacks was 33 per 100,000 population per year. The mortality rate for stroke for this population was 98/100,000 per year. The data on incidence of stroke and its type, its dependence on age and sex, and mortality rate are close to the corresponding data reported from other countries."} {"id": "PMID:1265820", "title": "Studies on Mediterranean leishmaniasis. IV. The leishmanin skin test in cutaneous leishmaniasis.", "content": "The leishmanin skin test was used in four different areas of the Italian Adriatic coast (Emilia Romagna, Marche, San Marino and Abruzzi), old endemic areas for cutaneous leishmaniasis. The test was found to be postitive in 80% of past infections, the 20% negative reactions being found in those who had been infected 20 or more years before. In the old endemic area of Teramo there was increasing positivity with age, with a sharp rise in the over 30 years age group suggesting that there had been a sudden break in transmission 30 years ago, coinciding with the DDT campaign of 1944-45. In San Marino in the past overt infection had occurred in a number of small microfoci, centred on houses surrounded by a larger number of inapparent infection. Control studies on a number of infectious and non-infectious diseases were all negative, and there was no relationship between tuberculin and leishmanin sensitivity.", "contents": "Studies on Mediterranean leishmaniasis. IV. The leishmanin skin test in cutaneous leishmaniasis. The leishmanin skin test was used in four different areas of the Italian Adriatic coast (Emilia Romagna, Marche, San Marino and Abruzzi), old endemic areas for cutaneous leishmaniasis. The test was found to be postitive in 80% of past infections, the 20% negative reactions being found in those who had been infected 20 or more years before. In the old endemic area of Teramo there was increasing positivity with age, with a sharp rise in the over 30 years age group suggesting that there had been a sudden break in transmission 30 years ago, coinciding with the DDT campaign of 1944-45. In San Marino in the past overt infection had occurred in a number of small microfoci, centred on houses surrounded by a larger number of inapparent infection. Control studies on a number of infectious and non-infectious diseases were all negative, and there was no relationship between tuberculin and leishmanin sensitivity."} {"id": "PMID:1265812", "title": "Abnormal cerebrovascular response to altered PaCO2 in baboons with obstructive jaundice.", "content": "The cerebrovascular response to hypercapnia and hyperventilation was studied in normal and jaundiced baboons by the intracarotid 133Xe injection technique. The baboons with bile duct ligation were found to have decreased CBF at all levels of PaCO2. This difference between normal and jaundiced baboons was 13% at normocapnia rising to 33% with hypercapnia and 37% with hypocapnia. The CBF values all were increased toward normal by use of an alpha-adrenoreceptor blockade (phentolamine). It is suggested that the obstructive jaundice potentiated an inherent vasoconstrictor alpha-adrenergic mechanism to oppose the effects of CO2. Also, alteration of the PaCO2 may have produced its effects on the cerebral vessels by altering this adrenergic mechanism.", "contents": "Abnormal cerebrovascular response to altered PaCO2 in baboons with obstructive jaundice. The cerebrovascular response to hypercapnia and hyperventilation was studied in normal and jaundiced baboons by the intracarotid 133Xe injection technique. The baboons with bile duct ligation were found to have decreased CBF at all levels of PaCO2. This difference between normal and jaundiced baboons was 13% at normocapnia rising to 33% with hypercapnia and 37% with hypocapnia. The CBF values all were increased toward normal by use of an alpha-adrenoreceptor blockade (phentolamine). It is suggested that the obstructive jaundice potentiated an inherent vasoconstrictor alpha-adrenergic mechanism to oppose the effects of CO2. Also, alteration of the PaCO2 may have produced its effects on the cerebral vessels by altering this adrenergic mechanism."} {"id": "PMID:1265821", "title": "Arbovirus infections in Sarawak: the role of the domestic pig.", "content": "The possible role of pigs as arbovirus maintenance hosts and their importance as amplifier hosts was studied. Blood samples from 464 pigs of all ages collected in 1962 and 1964 were tested against 10 arboviruses. Antibodies to Japanese encephalitis and Getah viruses were particularly prevalent and their calculated monthly infection rates were 19-5% and 13-3% respectively. In 1969, 447 pigs were bled monthly throughout the year and the infection rates for Japanese encephalitis virus were calculated in pigs during the first year of life. Infection rates were not uniform throughout the year; the rate increases as the pig grew older and there was a marked seasonal increase in the infection rate in the period from November to January. This coincided with the seasonal major population peak of Culex tritaeniorhynchus following intense breeding of this mosquito prior to rice planting. It is suggested that, in Sarawak, the pig acts as a maintenance host of Japanese encephalitis in a cycle involving C. gelidus mosquitoes and also acts as an important amplifier host towards the end of the year in a cycle involving C. tritaeniorhynchus. It is further suggested that Getah virus is maintained in a similar cycle between C. tritaeniorhynchus and pigs.", "contents": "Arbovirus infections in Sarawak: the role of the domestic pig. The possible role of pigs as arbovirus maintenance hosts and their importance as amplifier hosts was studied. Blood samples from 464 pigs of all ages collected in 1962 and 1964 were tested against 10 arboviruses. Antibodies to Japanese encephalitis and Getah viruses were particularly prevalent and their calculated monthly infection rates were 19-5% and 13-3% respectively. In 1969, 447 pigs were bled monthly throughout the year and the infection rates for Japanese encephalitis virus were calculated in pigs during the first year of life. Infection rates were not uniform throughout the year; the rate increases as the pig grew older and there was a marked seasonal increase in the infection rate in the period from November to January. This coincided with the seasonal major population peak of Culex tritaeniorhynchus following intense breeding of this mosquito prior to rice planting. It is suggested that, in Sarawak, the pig acts as a maintenance host of Japanese encephalitis in a cycle involving C. gelidus mosquitoes and also acts as an important amplifier host towards the end of the year in a cycle involving C. tritaeniorhynchus. It is further suggested that Getah virus is maintained in a similar cycle between C. tritaeniorhynchus and pigs."} {"id": "PMID:1265822", "title": "Schistosomal pigment in human and murine infections with Schistosoma mansoni.", "content": "Schistosomal pigment was studied by optical and electron microscopy in liver biopsies of patients with different clinical forms of schistosomiasis and in livers of mice experimentally infected with Schistosoma mansoni. Phagosomal and residual forms of the pigment are described. The quantity of pigment is low in subclinical and in hepatointestinal forms of schistosomiasis; it is high in young patients with the hepatosplenic form, and low in the old ones. The participation of the pigment in the pathogenesis of schistosomal lesions is discussed.", "contents": "Schistosomal pigment in human and murine infections with Schistosoma mansoni. Schistosomal pigment was studied by optical and electron microscopy in liver biopsies of patients with different clinical forms of schistosomiasis and in livers of mice experimentally infected with Schistosoma mansoni. Phagosomal and residual forms of the pigment are described. The quantity of pigment is low in subclinical and in hepatointestinal forms of schistosomiasis; it is high in young patients with the hepatosplenic form, and low in the old ones. The participation of the pigment in the pathogenesis of schistosomal lesions is discussed."} {"id": "PMID:1265823", "title": "Neurotoxic effects of bites by the Egyptian cobra (Naja haje) in Nigeria.", "content": "Two patients were bitten by Egyptian cobra (Naja haje). One became drowsy and developed transient ptosis 24 hours later. The other lost consciousness and died within two hours of the bite, but no cause was revealed by autopsy. A third patient developed severe transient neurological signs after being bitten by an unidentified snake. The small literature on bites by this species is discussed.", "contents": "Neurotoxic effects of bites by the Egyptian cobra (Naja haje) in Nigeria. Two patients were bitten by Egyptian cobra (Naja haje). One became drowsy and developed transient ptosis 24 hours later. The other lost consciousness and died within two hours of the bite, but no cause was revealed by autopsy. A third patient developed severe transient neurological signs after being bitten by an unidentified snake. The small literature on bites by this species is discussed."} {"id": "PMID:1265824", "title": "A septicaemic disease of East African snakes associated with enterobacteriaceae.", "content": "A bacterial epizootic disease of snakes at a snake farm in Kenya is described. The condition shows characteristic clinical signs and post mortem lesions and is characterized by a bacteraemia and septicaemia. The mortality rate is high and newly captured snakes die within a few weeks. Attempted control of the disease is discussed briefly and attention is drawn to the significance of such a condition in a commercial enterprise.", "contents": "A septicaemic disease of East African snakes associated with enterobacteriaceae. A bacterial epizootic disease of snakes at a snake farm in Kenya is described. The condition shows characteristic clinical signs and post mortem lesions and is characterized by a bacteraemia and septicaemia. The mortality rate is high and newly captured snakes die within a few weeks. Attempted control of the disease is discussed briefly and attention is drawn to the significance of such a condition in a commercial enterprise."} {"id": "PMID:1265825", "title": "Control of antivenom treatment in Echis carinatus (Carpet Viper) poisoning.", "content": "A study of all the patients treated for Echis carinatus bites in a rural mission hospital in Northern Nigeria in June 1973 showed that not all bleeding during recovery from an Echis bite results directly from the action of the venom; thus not all bleeding requires antivenom for treatment. Evenomation by Echis in West Africa is accompanied by incoagulability of the blood. If coagulability is assessed by a simply performed test, also described, on each occasion bleeding is suspected of being due to Echis venom and if antivenom is given only when incoagulability is demonstrated, expensive antivenom may be used more sparingly and to more benefit.", "contents": "Control of antivenom treatment in Echis carinatus (Carpet Viper) poisoning. A study of all the patients treated for Echis carinatus bites in a rural mission hospital in Northern Nigeria in June 1973 showed that not all bleeding during recovery from an Echis bite results directly from the action of the venom; thus not all bleeding requires antivenom for treatment. Evenomation by Echis in West Africa is accompanied by incoagulability of the blood. If coagulability is assessed by a simply performed test, also described, on each occasion bleeding is suspected of being due to Echis venom and if antivenom is given only when incoagulability is demonstrated, expensive antivenom may be used more sparingly and to more benefit."} {"id": "PMID:1265834", "title": "The management of typhoid fever.", "content": "The diagnosis of typhoid fever requires clinical alertness and ready laboratory support, blood cultures being most important. Chloramphenicol remains the standard drug specific for acute typhoid fever while cotrimoxazole is a useful alternative. Both of these are also useful in the treatment of relapses. The importance of supportive treatment cannot be over-emphasized. The treatment of intestinal complication is mainly conservative. Steroid is useful in the toxic delirious state. The management of chronic typhoid carriers is still an unsolved problem. To exclude the chronic carriers from handling food and to give advice on meticulous attention to personal hygiene is still the best way of public health control.", "contents": "The management of typhoid fever. The diagnosis of typhoid fever requires clinical alertness and ready laboratory support, blood cultures being most important. Chloramphenicol remains the standard drug specific for acute typhoid fever while cotrimoxazole is a useful alternative. Both of these are also useful in the treatment of relapses. The importance of supportive treatment cannot be over-emphasized. The treatment of intestinal complication is mainly conservative. Steroid is useful in the toxic delirious state. The management of chronic typhoid carriers is still an unsolved problem. To exclude the chronic carriers from handling food and to give advice on meticulous attention to personal hygiene is still the best way of public health control."} {"id": "PMID:1265837", "title": "Scrotal flap urethroplasty in the treatment of carcinoma of the penis.", "content": "Another use for the scrotal skin flap is described. It is an ideal method for dealing with carcinoma of the penis and prevents meatal stricture. It may be used to provide permanent urethrostomy in cases of chronic complicated urethral stricture where other types of operative treatment are unacceptable to the patient. It is recommended for use in situations where follow-up is difficult.", "contents": "Scrotal flap urethroplasty in the treatment of carcinoma of the penis. Another use for the scrotal skin flap is described. It is an ideal method for dealing with carcinoma of the penis and prevents meatal stricture. It may be used to provide permanent urethrostomy in cases of chronic complicated urethral stricture where other types of operative treatment are unacceptable to the patient. It is recommended for use in situations where follow-up is difficult."} {"id": "PMID:1265839", "title": "Sickle cell disease in pregnancy.", "content": "S-Homozygotes, SC heterozygotes, and S-beta-thalassaemia heterozygotes are the haemoglobinopathies which make up sickle cell disease. Although their clinical features are similar, as regards complications during pregnancy, Hb S-beta-thalassaemia most dangerous, the main causes of mortality being severe anemia, acute sequestration crisis, bacterial infections, painful episodes, and pulmonary bone marrow fat embolism. Folic acid and antimalarials (where these are indicated) are often successful in preventing severe anaemia. It is best to reserve blood transfusion to replace moderate loss or to correct gross anaemia quickly when this is considered severe enough to threaten life. Painful crises are particularly common towards the end of pregnancy and in treating these episodes, analgesics, antibiotics, and sometimes heparin are used. S-homozygote carries additional hazards. Because of the prevalence of pelvic contraction, fetopelvic disproportion is common and so the incidence of operative deliveries is high. Many fetuses are lost through an increased incidence of abortion and perinatal mortality. In the survivors, there is evidence of intrauterine growth retardation brought about by continuous maternal anaemia throughout pregnancy.", "contents": "Sickle cell disease in pregnancy. S-Homozygotes, SC heterozygotes, and S-beta-thalassaemia heterozygotes are the haemoglobinopathies which make up sickle cell disease. Although their clinical features are similar, as regards complications during pregnancy, Hb S-beta-thalassaemia most dangerous, the main causes of mortality being severe anemia, acute sequestration crisis, bacterial infections, painful episodes, and pulmonary bone marrow fat embolism. Folic acid and antimalarials (where these are indicated) are often successful in preventing severe anaemia. It is best to reserve blood transfusion to replace moderate loss or to correct gross anaemia quickly when this is considered severe enough to threaten life. Painful crises are particularly common towards the end of pregnancy and in treating these episodes, analgesics, antibiotics, and sometimes heparin are used. S-homozygote carries additional hazards. Because of the prevalence of pelvic contraction, fetopelvic disproportion is common and so the incidence of operative deliveries is high. Many fetuses are lost through an increased incidence of abortion and perinatal mortality. In the survivors, there is evidence of intrauterine growth retardation brought about by continuous maternal anaemia throughout pregnancy."} {"id": "PMID:1265923", "title": "Applications of spectral analysis in medical ultrasonography.", "content": "Spectral analysis of ultrasonic reflections from biological tissues can be used to determine basic tissue parameters for use in differential diagnosis. This paper describes the use of the technique under circumstances encountered in several types of clinical examinations. The applications are illustrated with results obtained from laboratory measurements with a system now being employed in a clinical evaluation programme. The test objects studied simulate tissues with planar boundaries, tissues with heterogeneous interior structure, and tissues causing acoustic 'shadowing' of posterior regions.", "contents": "Applications of spectral analysis in medical ultrasonography. Spectral analysis of ultrasonic reflections from biological tissues can be used to determine basic tissue parameters for use in differential diagnosis. This paper describes the use of the technique under circumstances encountered in several types of clinical examinations. The applications are illustrated with results obtained from laboratory measurements with a system now being employed in a clinical evaluation programme. The test objects studied simulate tissues with planar boundaries, tissues with heterogeneous interior structure, and tissues causing acoustic 'shadowing' of posterior regions."} {"id": "PMID:1265924", "title": "A critical analysis of ultrasonic therapy.", "content": "The authors have examined the effect of ultrasonic irradiation on myopy. Fourty-two eyes of 24 patients were treated. In more than 76% of the cases, there was an average decrease of 1.04 D in refraction. When myopy was accompanied by astigmatism, this also decreased or even disappeared.", "contents": "A critical analysis of ultrasonic therapy. The authors have examined the effect of ultrasonic irradiation on myopy. Fourty-two eyes of 24 patients were treated. In more than 76% of the cases, there was an average decrease of 1.04 D in refraction. When myopy was accompanied by astigmatism, this also decreased or even disappeared."} {"id": "PMID:1265925", "title": "Ultrasound spectroscopy applied to blood coagulation studies.", "content": "Two frequency scanning ultrasonic spectrographs utilizing time-delay signal processing techniques have been developed. These permit measurement of time delays (and hence velocity changes) in a sample in the order of 10(-8) s. The present instruments allow such measurements to be made continuously over a frequency range of 1-10 MHz. These instruments have been used to monitor changes in velocity as a function of frequency during coagulation in purified human fibrinogen solution and human plasma. It was found that velocity dispersion occurred at discrete frequencies during the coagulation process. The frequency dependent data is reproducible, although this depends to some extent upon the samples used. The instruments which were calibrated using a fixed length of coaxial cable, exhibit a high degree of reproducibility.", "contents": "Ultrasound spectroscopy applied to blood coagulation studies. Two frequency scanning ultrasonic spectrographs utilizing time-delay signal processing techniques have been developed. These permit measurement of time delays (and hence velocity changes) in a sample in the order of 10(-8) s. The present instruments allow such measurements to be made continuously over a frequency range of 1-10 MHz. These instruments have been used to monitor changes in velocity as a function of frequency during coagulation in purified human fibrinogen solution and human plasma. It was found that velocity dispersion occurred at discrete frequencies during the coagulation process. The frequency dependent data is reproducible, although this depends to some extent upon the samples used. The instruments which were calibrated using a fixed length of coaxial cable, exhibit a high degree of reproducibility."} {"id": "PMID:1265926", "title": "Controlled electrical bladder evacuation via stimulation of the sacral micturition center or direct detrusor stimulation.", "content": "Electrical stimulation of the spinal cord and of the detrusor was compared in 5 'acute' dogs. Strong detrusor contraction and rise in intravesical pressure were obtained either way but, with spinal cord stimulation, concomitant rise in urethral resistance prevented micturition. Stimulation with a bladder pacemaker induced detrusor contraction high enough to overcome outflow resistance, thus was more effective in initiating voiding.", "contents": "Controlled electrical bladder evacuation via stimulation of the sacral micturition center or direct detrusor stimulation. Electrical stimulation of the spinal cord and of the detrusor was compared in 5 'acute' dogs. Strong detrusor contraction and rise in intravesical pressure were obtained either way but, with spinal cord stimulation, concomitant rise in urethral resistance prevented micturition. Stimulation with a bladder pacemaker induced detrusor contraction high enough to overcome outflow resistance, thus was more effective in initiating voiding."} {"id": "PMID:1265927", "title": "The suspensory apparatus of the female bladder neck.", "content": "Lateral cystourethrograms have shown a forwards-downwards displacement of the bladder neck in bladder base insufficiency, a type of stress incontinence. In search for the structure which in normal subjects prevents this displacement, a series of 10 dissections of the female pelvic floor was undertaken. The formerly described structures: The pubo-vesical ligaments and the precervical arc are shown. As a new finding it is demonstrated how these structures are dependent on an upwards-backwards suspension by a strong ligament in the fascia over the levator muscle.", "contents": "The suspensory apparatus of the female bladder neck. Lateral cystourethrograms have shown a forwards-downwards displacement of the bladder neck in bladder base insufficiency, a type of stress incontinence. In search for the structure which in normal subjects prevents this displacement, a series of 10 dissections of the female pelvic floor was undertaken. The formerly described structures: The pubo-vesical ligaments and the precervical arc are shown. As a new finding it is demonstrated how these structures are dependent on an upwards-backwards suspension by a strong ligament in the fascia over the levator muscle."} {"id": "PMID:1265928", "title": "Pressure measurements in organic sphincteric zones.", "content": "A new method of measuring pressure is presented which serves to determine the opening pressures in organic sphincter areas and to investigate the behavior of the high-pressure zone and its susceptibility. By means of a pressure-measuring device which is introduced into the sphincter area, the opening pressure, which may be equated to the constant cloding pressure, can be determined by known increases of pressure. The method is described in detail, and the use of this manometric procedure is demonstrated with reference to the lower esophageal spinncter.", "contents": "Pressure measurements in organic sphincteric zones. A new method of measuring pressure is presented which serves to determine the opening pressures in organic sphincter areas and to investigate the behavior of the high-pressure zone and its susceptibility. By means of a pressure-measuring device which is introduced into the sphincter area, the opening pressure, which may be equated to the constant cloding pressure, can be determined by known increases of pressure. The method is described in detail, and the use of this manometric procedure is demonstrated with reference to the lower esophageal spinncter."} {"id": "PMID:1265929", "title": "Bladder and urethral recordings in acute and chronic spinal cord injury patients.", "content": "Three groups of patients with upper motor neuron lesions were studied. A first group consisted of 19 patients with complete lesions and 3 patients with incomplete lesions. All had an unbalanced bladder function which required surgical interventions. A second group consisted of 9 patients with chronic complete lesions who achieved balanced bladder function spontaneously. A third group consisted of 11 patients in the acute stage of injury. Polygraph recordings of pressure within the bladder, urethra, rectum and external anal sphincter were carried out with the help of video-tape monitoring and radiographic image intensification. Special catheter ballons with radiopaque markings were employed for pressure measurements. The behavior of the external urethral sphincter during spinal shock and the sequence of return of sacral somatic and visceral motor reflexes during recovery from spinal shock were investigated. It was shown that in spinal shock, the majority of patients retained sacral segment somatomotor reflex activity, in the absence of visceromotor activity, and that resistance values at the external urethral sphincter remained high. The highest resistance recorded in the membranous urethra was found to be located at the distal external sphincter, just before the bulb of the urethra.", "contents": "Bladder and urethral recordings in acute and chronic spinal cord injury patients. Three groups of patients with upper motor neuron lesions were studied. A first group consisted of 19 patients with complete lesions and 3 patients with incomplete lesions. All had an unbalanced bladder function which required surgical interventions. A second group consisted of 9 patients with chronic complete lesions who achieved balanced bladder function spontaneously. A third group consisted of 11 patients in the acute stage of injury. Polygraph recordings of pressure within the bladder, urethra, rectum and external anal sphincter were carried out with the help of video-tape monitoring and radiographic image intensification. Special catheter ballons with radiopaque markings were employed for pressure measurements. The behavior of the external urethral sphincter during spinal shock and the sequence of return of sacral somatic and visceral motor reflexes during recovery from spinal shock were investigated. It was shown that in spinal shock, the majority of patients retained sacral segment somatomotor reflex activity, in the absence of visceromotor activity, and that resistance values at the external urethral sphincter remained high. The highest resistance recorded in the membranous urethra was found to be located at the distal external sphincter, just before the bulb of the urethra."} {"id": "PMID:1265930", "title": "Detection of urine loss using the Exeter recording nappy and other similar devices.", "content": "A technical evaluation of the Exeter recording nappy has been carried out with particular reference to (a) linearity, (b) reproducibility of calibration, (c) the effect of variation in the position of moistened zones produced by consecutive leakages and (d) the effect of variation in the electrical conductivity of the liquid detected. The clinical use of the nappy is also discussed. A miniature alarm coupled to a similar pad arrangement has been developed as a training system for the geriatric incontinent patient and patients with neurogenic bladders. A 'pad and pant' version of an enuresis alarm has also been designed which had advantages over the conventional under-sheet type.", "contents": "Detection of urine loss using the Exeter recording nappy and other similar devices. A technical evaluation of the Exeter recording nappy has been carried out with particular reference to (a) linearity, (b) reproducibility of calibration, (c) the effect of variation in the position of moistened zones produced by consecutive leakages and (d) the effect of variation in the electrical conductivity of the liquid detected. The clinical use of the nappy is also discussed. A miniature alarm coupled to a similar pad arrangement has been developed as a training system for the geriatric incontinent patient and patients with neurogenic bladders. A 'pad and pant' version of an enuresis alarm has also been designed which had advantages over the conventional under-sheet type."} {"id": "PMID:1265931", "title": "Dysfunction of the bladder neck: a urodynamic study.", "content": "Urodynamic investigations were performed in 9 males, suffering from dysfunction of the bladder neck (detrusor bladder neck dyssynergia). The parameters of micturition were compared with the values in normal males and in patients with prostatic obstruction. By introducing a new factor, the maximum opening time, we found a characteristic pattern in dysfunction of the bladder neck, making selection of patients for endoscopic incision of the bladder neck possible. The maximum and mean flow rates increased significantly in 5 patients treated with incision of the bladder neck. The diagnostic value of voiding cystourethrography and urodynamic investigation is discussed.", "contents": "Dysfunction of the bladder neck: a urodynamic study. Urodynamic investigations were performed in 9 males, suffering from dysfunction of the bladder neck (detrusor bladder neck dyssynergia). The parameters of micturition were compared with the values in normal males and in patients with prostatic obstruction. By introducing a new factor, the maximum opening time, we found a characteristic pattern in dysfunction of the bladder neck, making selection of patients for endoscopic incision of the bladder neck possible. The maximum and mean flow rates increased significantly in 5 patients treated with incision of the bladder neck. The diagnostic value of voiding cystourethrography and urodynamic investigation is discussed."} {"id": "PMID:1265932", "title": "[Actinomycin-D therapy in testicular cancer (author's transl)].", "content": "In early stages of the disease the prognosis of testicular cancer has been improved mainly by the introduction of radical surgical procedures. Cytostatic treatment of metastasising testicular cancers has only been of limited value. Actinomycin D has been shown to be one of the most potent agents in malignant teratomas. Own results are presented for 21 eligible patients who received actinomycin D alone. One complete remission and 4-partial remissions were achieved giving an overall response rate of 19%. This precentage seems to be low compared to similar data in the current literature. The result may be explained by the selection of the patients with a high percentage showing far advanced disease before therapy was initiated. However, comparing the data presented with those from our own study on combination chemotherapy and with the more recent results in the literature, single agent chemotherapy does not seem to be the method of choice in metastasising testicular cancer. Improvement of the results by the integration of combination chemotherapy, hormonal therapy and irradiation will have to be based on prospective, controlled studies.", "contents": "[Actinomycin-D therapy in testicular cancer (author's transl)]. In early stages of the disease the prognosis of testicular cancer has been improved mainly by the introduction of radical surgical procedures. Cytostatic treatment of metastasising testicular cancers has only been of limited value. Actinomycin D has been shown to be one of the most potent agents in malignant teratomas. Own results are presented for 21 eligible patients who received actinomycin D alone. One complete remission and 4-partial remissions were achieved giving an overall response rate of 19%. This precentage seems to be low compared to similar data in the current literature. The result may be explained by the selection of the patients with a high percentage showing far advanced disease before therapy was initiated. However, comparing the data presented with those from our own study on combination chemotherapy and with the more recent results in the literature, single agent chemotherapy does not seem to be the method of choice in metastasising testicular cancer. Improvement of the results by the integration of combination chemotherapy, hormonal therapy and irradiation will have to be based on prospective, controlled studies."} {"id": "PMID:1265933", "title": "[Significance of digital examination in early diagnosis of prostate carcinoma (author's transl)].", "content": "Digital palpation of the prostate is not suitable for positive differentation between benign and malignant lesions of the prostate. Whenever a conspicuous finding is observed during a physical examination of the prostate a fine needle aspiration cytology is mandatory for eluidation of the disease. This procedure is simple and inexpensive, has a low rate of complications and high diagnostic validity.", "contents": "[Significance of digital examination in early diagnosis of prostate carcinoma (author's transl)]. Digital palpation of the prostate is not suitable for positive differentation between benign and malignant lesions of the prostate. Whenever a conspicuous finding is observed during a physical examination of the prostate a fine needle aspiration cytology is mandatory for eluidation of the disease. This procedure is simple and inexpensive, has a low rate of complications and high diagnostic validity."} {"id": "PMID:1265934", "title": "[Stauffer syndrome, paraneoplastic hepatic dysfunction syndrome associated with renal cell carcinoma (author's transl)].", "content": "In two patients with renal cell carcinoma, the following biochemical changes were found independently of hepatic metastases: increased alkaline phosphatase activity, rise in bromsulfothalein retention, hypoalbuminemia, increase in alpha2-globulin, and prolonged prothrombin time (Stauffer syndrome). In both cases the syndrome was found to be the first sign of the renal cell carcinoma. In one patient liver function returned to normal after removal of the neoplasm, in correlation with the good recovery. In the other case the abnormal laboratory findings persisted after total renal surgery. Clinically, diffuse pulmonary metastases occurred. Both case histories show the high significance in knowing Stauffer syndrome and its value for early diagnosis and operative success.", "contents": "[Stauffer syndrome, paraneoplastic hepatic dysfunction syndrome associated with renal cell carcinoma (author's transl)]. In two patients with renal cell carcinoma, the following biochemical changes were found independently of hepatic metastases: increased alkaline phosphatase activity, rise in bromsulfothalein retention, hypoalbuminemia, increase in alpha2-globulin, and prolonged prothrombin time (Stauffer syndrome). In both cases the syndrome was found to be the first sign of the renal cell carcinoma. In one patient liver function returned to normal after removal of the neoplasm, in correlation with the good recovery. In the other case the abnormal laboratory findings persisted after total renal surgery. Clinically, diffuse pulmonary metastases occurred. Both case histories show the high significance in knowing Stauffer syndrome and its value for early diagnosis and operative success."} {"id": "PMID:1265935", "title": "[Simultaneous occurrence of a malignent teratoma in the left testis and a seminoma in the right testis (author's transl)].", "content": "A twenty-three year old patient had simultaneously a left sided seminoma and a right sided malignant teratoma. Two years later a left nephrectomy had to be carried out because of left paraaortic and renal metastases. The patient received radiation therapy and cytostatic therapy with Velbe, Actinomycin D and Prednisone and survived five years with few symptoms. He died with multiple metastases following paraplegia due to a T 4/5 lesion.", "contents": "[Simultaneous occurrence of a malignent teratoma in the left testis and a seminoma in the right testis (author's transl)]. A twenty-three year old patient had simultaneously a left sided seminoma and a right sided malignant teratoma. Two years later a left nephrectomy had to be carried out because of left paraaortic and renal metastases. The patient received radiation therapy and cytostatic therapy with Velbe, Actinomycin D and Prednisone and survived five years with few symptoms. He died with multiple metastases following paraplegia due to a T 4/5 lesion."} {"id": "PMID:1265936", "title": "[The clinical significance of extratesticular originating tumors (author's transl)].", "content": "A case of large retroperitoneal metastasis of a seminoma is demonstrated. The primary tumor was impossible to recognize clinically. The extremely scarred primary tumor was at last discovered histologically in the normal appearing testis on the same side. This experience leads to the conclusion that the diagnosis \"extratesticular originating testicular tumor\" not be accepted unless a \"burned-out\" tumor can be exluded histologically in the ipsilateral testis.", "contents": "[The clinical significance of extratesticular originating tumors (author's transl)]. A case of large retroperitoneal metastasis of a seminoma is demonstrated. The primary tumor was impossible to recognize clinically. The extremely scarred primary tumor was at last discovered histologically in the normal appearing testis on the same side. This experience leads to the conclusion that the diagnosis \"extratesticular originating testicular tumor\" not be accepted unless a \"burned-out\" tumor can be exluded histologically in the ipsilateral testis."} {"id": "PMID:1265937", "title": "[Late complications of the intestine after radiotherapy of bladder carcinoma].", "content": "Immediate reactions of the intestines during or after radiotherapy of the pelvis are very common. Later complications requiring surgical intervention are seldom found. Out of 101 patients with bladder carcinomas, we observed 4 with severe irreversible intestinal changes. These had been operated and had received post-operative radiotherapy. On 3 patients a sigmoid stenosis had to be resected under the protection of a colostomy. On the fourth patient an ileovesical fistula was closed primary.", "contents": "[Late complications of the intestine after radiotherapy of bladder carcinoma]. Immediate reactions of the intestines during or after radiotherapy of the pelvis are very common. Later complications requiring surgical intervention are seldom found. Out of 101 patients with bladder carcinomas, we observed 4 with severe irreversible intestinal changes. These had been operated and had received post-operative radiotherapy. On 3 patients a sigmoid stenosis had to be resected under the protection of a colostomy. On the fourth patient an ileovesical fistula was closed primary."} {"id": "PMID:1265939", "title": "Ureteroureterostomy and unilateral nephrostomy. Alternate rapid method of diversion.", "content": "Ureteroureterostomy with a Silastic nephrostomy has been utilized in 3 patients as a temporary diversion. It is a short procedure which is performed transabdominally and is well tolerated. It may be indicated in selected patients who will not be able to handle an appliance and cannot tolerate major surgery. This is not a panacea for urinary diversion, but in selected cases it may be applicable.", "contents": "Ureteroureterostomy and unilateral nephrostomy. Alternate rapid method of diversion. Ureteroureterostomy with a Silastic nephrostomy has been utilized in 3 patients as a temporary diversion. It is a short procedure which is performed transabdominally and is well tolerated. It may be indicated in selected patients who will not be able to handle an appliance and cannot tolerate major surgery. This is not a panacea for urinary diversion, but in selected cases it may be applicable."} {"id": "PMID:1265940", "title": "Innervation of trigonal area of canine urinary bladder.", "content": "Adrenergic and cholinergic histochemical staining techniques and in vitro muscle strip responses to adrenergic and cholinergic stimulation and blockade have failed to demonstrate any neuromorphologic or neuropharmacologic differences between the musculature of the canine trigone and that of the underlying detrusor. There is no evidence to suggest that a functional potential could be attributed to the trigone separate from that of the related bladder base.", "contents": "Innervation of trigonal area of canine urinary bladder. Adrenergic and cholinergic histochemical staining techniques and in vitro muscle strip responses to adrenergic and cholinergic stimulation and blockade have failed to demonstrate any neuromorphologic or neuropharmacologic differences between the musculature of the canine trigone and that of the underlying detrusor. There is no evidence to suggest that a functional potential could be attributed to the trigone separate from that of the related bladder base."} {"id": "PMID:1265941", "title": "Uninhibited neurogenic bladder in adults.", "content": "The uninhibited neurogenic bladder is a common entity. It is characterized by urge incontinence, frequency, enuresis, and recurrent urinary tract infections. The diagnosis can only be made by a thorough urologic investigation, including cystometrography. A sound treatment program involves the use of anticholinergic medication to abolish uninhibited contractions, frequent voiding to keep intravesical pressure low, and antibiotic treatment when indicated for concurrent infection.", "contents": "Uninhibited neurogenic bladder in adults. The uninhibited neurogenic bladder is a common entity. It is characterized by urge incontinence, frequency, enuresis, and recurrent urinary tract infections. The diagnosis can only be made by a thorough urologic investigation, including cystometrography. A sound treatment program involves the use of anticholinergic medication to abolish uninhibited contractions, frequent voiding to keep intravesical pressure low, and antibiotic treatment when indicated for concurrent infection."} {"id": "PMID:1265942", "title": "Electrohydraulic cystolithotripsy.", "content": "The protocol and technique of electrohydraulic cystolithotripsy with the SD-1 for the crushing of the bladder calculi is outlined. In our opinion, the instrument is safe and an effective adjunct to the urologist. Urate, phosphate, and carbonate calculi are easy to crush. Oxalate and uric acid stones are more resistant to fragmentation. The procedure is superior to the conventional methods with blind or optical lithotriptors. The method is easy to learn, and application of this technique may be combined in the same session with other urologic procedures; this procedure opens up a new avenue in the treatment of urinary calculous disease.", "contents": "Electrohydraulic cystolithotripsy. The protocol and technique of electrohydraulic cystolithotripsy with the SD-1 for the crushing of the bladder calculi is outlined. In our opinion, the instrument is safe and an effective adjunct to the urologist. Urate, phosphate, and carbonate calculi are easy to crush. Oxalate and uric acid stones are more resistant to fragmentation. The procedure is superior to the conventional methods with blind or optical lithotriptors. The method is easy to learn, and application of this technique may be combined in the same session with other urologic procedures; this procedure opens up a new avenue in the treatment of urinary calculous disease."} {"id": "PMID:1265943", "title": "Hydrocelectomy. Evaluation of technique.", "content": "A quick, simple, safe, and efficient means of hydrocelectomy is presented. The technique consists of extruding and fixing the testicle into a scrotal pouch. Twenty hydroceles were repaired without complication or recurrence.", "contents": "Hydrocelectomy. Evaluation of technique. A quick, simple, safe, and efficient means of hydrocelectomy is presented. The technique consists of extruding and fixing the testicle into a scrotal pouch. Twenty hydroceles were repaired without complication or recurrence."} {"id": "PMID:1265945", "title": "Penile prosthesis: psychologic factors.", "content": "A thirty-one-year-old paraplegic male requested a penile prosthesis. Psychiatric evaluations were done of both the patient and his wife. Within seventy-two hours of his arriving home with the prosthesis installed, his wife left their house to seek a divorce. The implications of this event for selecting patients for such devices are explored. Reservations are expressed about a prosthesis being inserted for patients married after the onset of impotence.", "contents": "Penile prosthesis: psychologic factors. A thirty-one-year-old paraplegic male requested a penile prosthesis. Psychiatric evaluations were done of both the patient and his wife. Within seventy-two hours of his arriving home with the prosthesis installed, his wife left their house to seek a divorce. The implications of this event for selecting patients for such devices are explored. Reservations are expressed about a prosthesis being inserted for patients married after the onset of impotence."} {"id": "PMID:1265946", "title": "Penile reconstruction in irradiated patient.", "content": "Reconstruction of a penis using a modified Gillies technique was performed on a forty-one-year-old man who had a total penectomy, inguinal node dissection, and 6,000 rads of cobalt-60 irradiation for carcinoma of the penis. The three different surgical techniques for reconstructing the penis are discussed in detail. It is our belief that reconstruction of a urethra and placement of a baculum in penile reconstruction after radiation therapy have more disadvantages than advantages. The literature is reviewed.", "contents": "Penile reconstruction in irradiated patient. Reconstruction of a penis using a modified Gillies technique was performed on a forty-one-year-old man who had a total penectomy, inguinal node dissection, and 6,000 rads of cobalt-60 irradiation for carcinoma of the penis. The three different surgical techniques for reconstructing the penis are discussed in detail. It is our belief that reconstruction of a urethra and placement of a baculum in penile reconstruction after radiation therapy have more disadvantages than advantages. The literature is reviewed."} {"id": "PMID:1265947", "title": "Hereditary nephritis associated with vesicoureteral reflux and vaginal duplication.", "content": "The concomitant occurrence of vesicoureteral reflux and hereditary nephritis has not been previously reported. A case of a patient with hereditary nephritis, vesicoureteral reflux, and vaginal duplication is presented and the related literature reviewed. It is suggested that familial reflux may occur significantly in families with hereditary nephritis.", "contents": "Hereditary nephritis associated with vesicoureteral reflux and vaginal duplication. The concomitant occurrence of vesicoureteral reflux and hereditary nephritis has not been previously reported. A case of a patient with hereditary nephritis, vesicoureteral reflux, and vaginal duplication is presented and the related literature reviewed. It is suggested that familial reflux may occur significantly in families with hereditary nephritis."} {"id": "PMID:1265952", "title": "Radiographic evaluation of renal excursion with respiration.", "content": "An unusual case stimulated investigation of radiographic changes in renal axis resulting from respiratory excursion. Prospective study of 20 \"routine\" excretory urograms revealed no statistically significant differences in renal axis whether the film was taken in full expiration or inspiration. Clinical implications and a review of pertinent literature are discussed.", "contents": "Radiographic evaluation of renal excursion with respiration. An unusual case stimulated investigation of radiographic changes in renal axis resulting from respiratory excursion. Prospective study of 20 \"routine\" excretory urograms revealed no statistically significant differences in renal axis whether the film was taken in full expiration or inspiration. Clinical implications and a review of pertinent literature are discussed."} {"id": "PMID:1265983", "title": "Effect of frequent ejaculation on semen characteristics in rams.", "content": "Sixteen Suffolk rams were ejaculated repeatedly for a period of eight hours during the month of November. Ejaculates were examined for semen characteristics. Volume density and number of sperm per ejaculate declined significantly in successive ejaculates. Motility and percentage abnormal sperm were not affected by frequent collection. It is concluded that the number of sperm per ejaculate, after the eighth ejaculate, could fall below that required for fertilisation to occur, particularly in progestagen treated ewes.", "contents": "Effect of frequent ejaculation on semen characteristics in rams. Sixteen Suffolk rams were ejaculated repeatedly for a period of eight hours during the month of November. Ejaculates were examined for semen characteristics. Volume density and number of sperm per ejaculate declined significantly in successive ejaculates. Motility and percentage abnormal sperm were not affected by frequent collection. It is concluded that the number of sperm per ejaculate, after the eighth ejaculate, could fall below that required for fertilisation to occur, particularly in progestagen treated ewes."} {"id": "PMID:1265985", "title": "Isolation of mycoplasmas from the respiratory tract of horses in Australia.", "content": "Mycoplasmas were isolated from two of 43 nasal swabs taken from live horses, and from one of 28 tracheal swabs taken from slaughtered horses. The slaughtered horse that yielded mycoplasmas had no gross pathological changes in the respiratory tract, but the nasal isolations were made from horses with rhinitis. The three mycoplasmas could be distinguished by cultural characteristics, and probably they represent three different species.", "contents": "Isolation of mycoplasmas from the respiratory tract of horses in Australia. Mycoplasmas were isolated from two of 43 nasal swabs taken from live horses, and from one of 28 tracheal swabs taken from slaughtered horses. The slaughtered horse that yielded mycoplasmas had no gross pathological changes in the respiratory tract, but the nasal isolations were made from horses with rhinitis. The three mycoplasmas could be distinguished by cultural characteristics, and probably they represent three different species."} {"id": "PMID:1265991", "title": "Snout-rubbing as a vice in weaned pigs.", "content": "Snout rubbing led to ulceration and necrosis in pigs subjected to it. Only animals of specific colouring were attacked.", "contents": "Snout-rubbing as a vice in weaned pigs. Snout rubbing led to ulceration and necrosis in pigs subjected to it. Only animals of specific colouring were attacked."} {"id": "PMID:1265992", "title": "The contribution of horned cattle to carcase bruising.", "content": "Five trials were conducted to evaluate the effects of the presence of horns on cattle on carcase bruising. In each trial there were three groups of cattle, hornless, horned and mixed (some with hrons and some without). The weight of bruised tissue trimmed from the carcases of the cattle in the horned groups was significantly greater than that trimmed from the carcases of the cattle in the hornless groups. When horned and hornless cattle are mixed the hornless animals in the mixed group sustain significantly more bruising than animals in a group consisting soley of hornless animals while the horned animals in a mixed group have a similar degree of bruising to cattle in a group consisting solely of horned cattle.", "contents": "The contribution of horned cattle to carcase bruising. Five trials were conducted to evaluate the effects of the presence of horns on cattle on carcase bruising. In each trial there were three groups of cattle, hornless, horned and mixed (some with hrons and some without). The weight of bruised tissue trimmed from the carcases of the cattle in the horned groups was significantly greater than that trimmed from the carcases of the cattle in the hornless groups. When horned and hornless cattle are mixed the hornless animals in the mixed group sustain significantly more bruising than animals in a group consisting soley of hornless animals while the horned animals in a mixed group have a similar degree of bruising to cattle in a group consisting solely of horned cattle."} {"id": "PMID:1265995", "title": "Cervical scoliosis and kidney lesions in sheep following dosage with vitamin D.", "content": "A case of cervical deformity of lambs following dosage with vitamin D was investigated. The lesions of a scoliosis are described together with the kidney lesions. It is suggested that doses of vitamin D normally considered to be non-toxic to sheep may prove to be so under certain conditions.", "contents": "Cervical scoliosis and kidney lesions in sheep following dosage with vitamin D. A case of cervical deformity of lambs following dosage with vitamin D was investigated. The lesions of a scoliosis are described together with the kidney lesions. It is suggested that doses of vitamin D normally considered to be non-toxic to sheep may prove to be so under certain conditions."} {"id": "PMID:1265996", "title": "Factors affecting the incidence of pneumonia in growing bulls.", "content": "The occurrence of respiratory disease at two Meat and Livestock Commission bull performance test centres over a period of three years is assessed. During this period a change in the system of testing was introduced so as to allow younger bulls to enter the centre and also to increase their throughput. This resulted in an increase in the incidence of pneumonia of more than five times. The management at one centre was changed to counteract this disease problem and the level of pneumonia was greatly reduced. Most respiratory disease occurred within the first month of entry to the centres. There was more infection during the second half of the year and especially in the October to December quarter. There appeared to be some relationship between the time bulls were weaned prior to entry to the centres and the incidence of pneumonia.", "contents": "Factors affecting the incidence of pneumonia in growing bulls. The occurrence of respiratory disease at two Meat and Livestock Commission bull performance test centres over a period of three years is assessed. During this period a change in the system of testing was introduced so as to allow younger bulls to enter the centre and also to increase their throughput. This resulted in an increase in the incidence of pneumonia of more than five times. The management at one centre was changed to counteract this disease problem and the level of pneumonia was greatly reduced. Most respiratory disease occurred within the first month of entry to the centres. There was more infection during the second half of the year and especially in the October to December quarter. There appeared to be some relationship between the time bulls were weaned prior to entry to the centres and the incidence of pneumonia."} {"id": "PMID:1265997", "title": "Prevention of traumatic indigestion in cattle.", "content": "The incidence of traumatic indigestion in an industrialised agricultural country, the economic losses due to the disease, and its prevention by use of a permanent reticular magnet are reviewed.", "contents": "Prevention of traumatic indigestion in cattle. The incidence of traumatic indigestion in an industrialised agricultural country, the economic losses due to the disease, and its prevention by use of a permanent reticular magnet are reviewed."} {"id": "PMID:1265998", "title": "Intestinal flora studies in rabbit mucoid enteritis.", "content": "The clinical and bacteriological examination of spontaneous and experimental cases of mucoid enteritis on a large rabbit farm indicated that the mucin accumulations in the colon are a consequence of constipation. This opinion is supported by the results obtained following ligation of the proximal colon. These findings suggest that rabbit mucoid enteritis is not a specific disease entity but a general response to the factors which cause constipation. Studies of the bacterial flora of the gut in spontaneous and experimental cases suggest that while there is a notable increase in the number of coliforms and clostridia over the healthy controls, these organisms only play a secondary role.", "contents": "Intestinal flora studies in rabbit mucoid enteritis. The clinical and bacteriological examination of spontaneous and experimental cases of mucoid enteritis on a large rabbit farm indicated that the mucin accumulations in the colon are a consequence of constipation. This opinion is supported by the results obtained following ligation of the proximal colon. These findings suggest that rabbit mucoid enteritis is not a specific disease entity but a general response to the factors which cause constipation. Studies of the bacterial flora of the gut in spontaneous and experimental cases suggest that while there is a notable increase in the number of coliforms and clostridia over the healthy controls, these organisms only play a secondary role."} {"id": "PMID:1266115", "title": "[Aneuploidy in focal adenomatosis as a risk factor for the development of breast cancer].", "content": "The study of the DNA content in nuclei of the mammary gland epithelium in 18 females with fibroadenomatosis, followed by breast cancer, and in 47 patients showing fibroadenomatosis, but no cancer subsequently, indicated that the presence of aneuploid cells in fibroadenomatous foci may be regarded as one of high risk factors of breast cancer incidence. In these patients the risk for breast cancer is 9 times as that in the remaining subjects with fibroadenomatosis.", "contents": "[Aneuploidy in focal adenomatosis as a risk factor for the development of breast cancer]. The study of the DNA content in nuclei of the mammary gland epithelium in 18 females with fibroadenomatosis, followed by breast cancer, and in 47 patients showing fibroadenomatosis, but no cancer subsequently, indicated that the presence of aneuploid cells in fibroadenomatous foci may be regarded as one of high risk factors of breast cancer incidence. In these patients the risk for breast cancer is 9 times as that in the remaining subjects with fibroadenomatosis."} {"id": "PMID:1266116", "title": "[Value of the method of dose fractionation in external irradiation of the lesser pelvis in patients with cancer of the cervix uteri].", "content": "Five-year results of treatment in 661 patients with cervical cancer depending on the technic of dose fractionation in external irradiation of the lesser pelvis under static gamma therapy are reported. Two methods of fractionation were employed: small (daily irradiation, the single focal dose of 125--150 rad) and average dose fractionation (irradiation 3 times a week, focal dosage--280--330 rad). In similar initial data (age, stage of the disease, a form of tumor growth and its histological structure) both with the combined and associated radiotherapy the best five-year results were gained with average dose fractionation.", "contents": "[Value of the method of dose fractionation in external irradiation of the lesser pelvis in patients with cancer of the cervix uteri]. Five-year results of treatment in 661 patients with cervical cancer depending on the technic of dose fractionation in external irradiation of the lesser pelvis under static gamma therapy are reported. Two methods of fractionation were employed: small (daily irradiation, the single focal dose of 125--150 rad) and average dose fractionation (irradiation 3 times a week, focal dosage--280--330 rad). In similar initial data (age, stage of the disease, a form of tumor growth and its histological structure) both with the combined and associated radiotherapy the best five-year results were gained with average dose fractionation."} {"id": "PMID:1266118", "title": "[Glycogen level in endometrial cancer].", "content": "Studies on glycogen metabolism in tissues of endometrial cancer with various morphological structure have indicated that in most cases irrespective of the level of differentiation endometrial tumors contain no glycogen and show a slight activity of glycogensynthetase, phosphorylase and oxido-reductive enzymes. However, among the tumors under study there may be cases, which are characterized by a high content of glycogen and enzymes related with its metabolism. In these patients endometrial cancer was preceded by persistant disorders in the menstrual cycle. The relation between two types of the glycogen metabolism in endometrial cancer and the state of endogenous hormonal background is discussed.", "contents": "[Glycogen level in endometrial cancer]. Studies on glycogen metabolism in tissues of endometrial cancer with various morphological structure have indicated that in most cases irrespective of the level of differentiation endometrial tumors contain no glycogen and show a slight activity of glycogensynthetase, phosphorylase and oxido-reductive enzymes. However, among the tumors under study there may be cases, which are characterized by a high content of glycogen and enzymes related with its metabolism. In these patients endometrial cancer was preceded by persistant disorders in the menstrual cycle. The relation between two types of the glycogen metabolism in endometrial cancer and the state of endogenous hormonal background is discussed."} {"id": "PMID:1266119", "title": "[Survival of patients with malignant tumors of the ovaries in relation to the stage according to the TNM classification].", "content": "To study the survival of patients in different spread of malignant tumors, the data on 419 patients with serous cystadenocarcinomas of the ovaries were analysed. Late results of treatment in these patients classified by 4 stages did not differ from the routinely observed issues. In staging of the tumor process in these patients according to the TNM system four variants in the degree of the process extension corresponded to each stage, which gave a precise idea as to the extent of the process not only judging by the primary focus condition, but also by metastases spread, thus enabling one to have a complete and proper knowledge of the true extension of the disease.", "contents": "[Survival of patients with malignant tumors of the ovaries in relation to the stage according to the TNM classification]. To study the survival of patients in different spread of malignant tumors, the data on 419 patients with serous cystadenocarcinomas of the ovaries were analysed. Late results of treatment in these patients classified by 4 stages did not differ from the routinely observed issues. In staging of the tumor process in these patients according to the TNM system four variants in the degree of the process extension corresponded to each stage, which gave a precise idea as to the extent of the process not only judging by the primary focus condition, but also by metastases spread, thus enabling one to have a complete and proper knowledge of the true extension of the disease."} {"id": "PMID:1266120", "title": "[Activity of hexokinase isoenzymes in the nuclei of cell cultures infected with oncogenic type-12 adenovirus].", "content": "The isoenzymic spectrum of a glycolytic enzyme-hexokinase (HK. 2,7.1.1) in the globuline fraction of cell nuclei of rat embryo fibroblasts (REF), infected with human adenovirus of type 12, was studied at 3, 5, 8, 18, 24 days of cultivation. Control studies revealed 3 hexokinase isoenzymes, the third one showing the highest activity and electromobility. In cultures under experiment the first enzyme was found to be lost at 5, 8, 18 days of infection and its activity to be enhanced on the 24th day. The activity of enzymes II and III increased yet on the 3d day of the culture infection. These alterations were especially pronounced to the start of morphological transformation (18th day) and at the 24th day, when the culture was entirely transformed.", "contents": "[Activity of hexokinase isoenzymes in the nuclei of cell cultures infected with oncogenic type-12 adenovirus]. The isoenzymic spectrum of a glycolytic enzyme-hexokinase (HK. 2,7.1.1) in the globuline fraction of cell nuclei of rat embryo fibroblasts (REF), infected with human adenovirus of type 12, was studied at 3, 5, 8, 18, 24 days of cultivation. Control studies revealed 3 hexokinase isoenzymes, the third one showing the highest activity and electromobility. In cultures under experiment the first enzyme was found to be lost at 5, 8, 18 days of infection and its activity to be enhanced on the 24th day. The activity of enzymes II and III increased yet on the 3d day of the culture infection. These alterations were especially pronounced to the start of morphological transformation (18th day) and at the 24th day, when the culture was entirely transformed."} {"id": "PMID:1266121", "title": "[Dynamics of changes in enterochromaffin cells during tumor growth].", "content": "A distinct correlation was found between changes in enterochromaffin cells producing highly active chemical substances--melatonin and serotonin, and stages of the neoplastic process. In early stages of tumor development a marked hyperplasia of enterochromaffin cells was noted, that was associated with enhancement of their histochemical properties. In advanced forms of cancer and chronic leucosis the number of cells is markedly reduced with simultaneous diminishing of their staining by specific histochemical methods. Such kinetics of changes of enterochromaffin cells appears to be related with definite antiblastic properties inherent to them and their products (melatonin and serotonin).", "contents": "[Dynamics of changes in enterochromaffin cells during tumor growth]. A distinct correlation was found between changes in enterochromaffin cells producing highly active chemical substances--melatonin and serotonin, and stages of the neoplastic process. In early stages of tumor development a marked hyperplasia of enterochromaffin cells was noted, that was associated with enhancement of their histochemical properties. In advanced forms of cancer and chronic leucosis the number of cells is markedly reduced with simultaneous diminishing of their staining by specific histochemical methods. Such kinetics of changes of enterochromaffin cells appears to be related with definite antiblastic properties inherent to them and their products (melatonin and serotonin)."} {"id": "PMID:1266122", "title": "[DNA metabolism in the immunocompetent organs of C57BL mice in chemical carcinogenesis].", "content": "DNA synthesis was determined in small lymphocytes nuclei in mice C57BL during the process of methylcholanthrene induced carcinogenesis. Both in the pretumor period and in animals with a tumor the DNA synthesis in lymph node lymphocytes nuclei was found to be decreased. Inhibition of the DNA synthesis is greatly pronounced in lymphocytes adjacent to the site of lymph node tumor development.", "contents": "[DNA metabolism in the immunocompetent organs of C57BL mice in chemical carcinogenesis]. DNA synthesis was determined in small lymphocytes nuclei in mice C57BL during the process of methylcholanthrene induced carcinogenesis. Both in the pretumor period and in animals with a tumor the DNA synthesis in lymph node lymphocytes nuclei was found to be decreased. Inhibition of the DNA synthesis is greatly pronounced in lymphocytes adjacent to the site of lymph node tumor development."} {"id": "PMID:1266123", "title": "[Influence of immunodepressants on transplanted ovarian tumors in rats].", "content": "Under study was the effect of hydrocortisone injection and x-ray irradiation in a recipient on the development of a transplanted ovarian tumor in rats. The irradiation was shown to have a greater stimulating effect on the neoplastic growth than hydrocortisone.", "contents": "[Influence of immunodepressants on transplanted ovarian tumors in rats]. Under study was the effect of hydrocortisone injection and x-ray irradiation in a recipient on the development of a transplanted ovarian tumor in rats. The irradiation was shown to have a greater stimulating effect on the neoplastic growth than hydrocortisone."} {"id": "PMID:1266124", "title": "[Results of epidemiological studies of primary cancer of the liver in the Tiumen district].", "content": "The study of the records of Tjumen Province postmortem rooms indicated a relattively high specific weight of primary cancer of the liver. Data on 1225 patients for the period of 1962-1971 are presented. The morbidity per 100 000 of population--12.5. The highest index--in Khanty-Mansy District--20.7, while a standard index--22.08. The zone of the highest incidence of primary cancer of the liver coincides with a relatively high opisthordiasis morbidity. Due to opisthordiasis tumors of the cholangiocellular structure arise in males as frequently as in females.", "contents": "[Results of epidemiological studies of primary cancer of the liver in the Tiumen district]. The study of the records of Tjumen Province postmortem rooms indicated a relattively high specific weight of primary cancer of the liver. Data on 1225 patients for the period of 1962-1971 are presented. The morbidity per 100 000 of population--12.5. The highest index--in Khanty-Mansy District--20.7, while a standard index--22.08. The zone of the highest incidence of primary cancer of the liver coincides with a relatively high opisthordiasis morbidity. Due to opisthordiasis tumors of the cholangiocellular structure arise in males as frequently as in females."} {"id": "PMID:1266180", "title": "[Itsenko-Cusing syndrome in hypohyseal adenoma].", "content": "A case observed at the Insitute of Endocrinology, Gerontology, and Geriatry is reported with Icenko--Cushing syndrome developed in consequence of hypophyseal adenoma. The telegammatherapy (total focal dose 4760 rads) carried out in the course of one year led to a complete regression of the developed alterations-- elimination of the redistribution of fats, restoration of the face normal colour and oval, nails and hair normalization as well as of cortisolemia and decrease in the osteoporosis degree with consolidation of the pathological fractures. Blood pressure (without hypotensive treatment) within normal values--140/90.", "contents": "[Itsenko-Cusing syndrome in hypohyseal adenoma]. A case observed at the Insitute of Endocrinology, Gerontology, and Geriatry is reported with Icenko--Cushing syndrome developed in consequence of hypophyseal adenoma. The telegammatherapy (total focal dose 4760 rads) carried out in the course of one year led to a complete regression of the developed alterations-- elimination of the redistribution of fats, restoration of the face normal colour and oval, nails and hair normalization as well as of cortisolemia and decrease in the osteoporosis degree with consolidation of the pathological fractures. Blood pressure (without hypotensive treatment) within normal values--140/90."} {"id": "PMID:1266212", "title": "Myocardial revascularization in high-risk coronary patients.", "content": "It is recognized that postoperative mortality, infarction and the need for inotropic support are increased following myocardial revascularization in highrisk patients. Operations were carried out in 57 such patients in whom one or more of the following factors were present: ventricular dysfunction-ejection fraction less than 0.4 (17), unstable (8) or preinfarction angina (29), evolving infarction (8), recent infarction (less than two weeks before) (5) and refractory ventricular tachyarrhythmia (4). Combined risk factors were present in nine patients. The following principles were utilized to minimize ischemic injury: (1) avoidance of prebypass hypertension and hypotension, (2) avoidance of extreme hemodilution, (3) avoidance of ventricular fibrillation, (4) maintenance of beating empty heart, when possible, (5) the limiting of ischemic periods to less than 12 minutes (hypothermia 32 degrees C) and (6) repaying myocardial oxygen debt with total (vented) bypass, when necessary. The following results were obtained: inotropic support was required in five patients (9 percent), \"new\" postoperative infarction occurred in five patients (9 percent) and one patient died (2 percent). These results are comparable to those reported in good-risk patients, and indicate that optimal myocardial protection will allow safe revascularization in a high-risk patient.", "contents": "Myocardial revascularization in high-risk coronary patients. It is recognized that postoperative mortality, infarction and the need for inotropic support are increased following myocardial revascularization in highrisk patients. Operations were carried out in 57 such patients in whom one or more of the following factors were present: ventricular dysfunction-ejection fraction less than 0.4 (17), unstable (8) or preinfarction angina (29), evolving infarction (8), recent infarction (less than two weeks before) (5) and refractory ventricular tachyarrhythmia (4). Combined risk factors were present in nine patients. The following principles were utilized to minimize ischemic injury: (1) avoidance of prebypass hypertension and hypotension, (2) avoidance of extreme hemodilution, (3) avoidance of ventricular fibrillation, (4) maintenance of beating empty heart, when possible, (5) the limiting of ischemic periods to less than 12 minutes (hypothermia 32 degrees C) and (6) repaying myocardial oxygen debt with total (vented) bypass, when necessary. The following results were obtained: inotropic support was required in five patients (9 percent), \"new\" postoperative infarction occurred in five patients (9 percent) and one patient died (2 percent). These results are comparable to those reported in good-risk patients, and indicate that optimal myocardial protection will allow safe revascularization in a high-risk patient."} {"id": "PMID:1266213", "title": "Tattoo removal by split thickness tangential excision.", "content": "Split thickness tangential excision is a simple means of tattoo removal with very acceptable cosmetic results. The technique has several advantages. (1) The depth of skin removal may accurately be controlled as the tattoo pigment is excised with a dermatome. The major portion, if not all of the remaining pigment, is extruded and sloughs with the crust. (2) Scar formation, if it occurs at all, is negligible. (3) No donor site is created. (4) The procedure may be carried out rapidly without admitting patients to hospital, is inexpensive for patients and conserves time for physicians.", "contents": "Tattoo removal by split thickness tangential excision. Split thickness tangential excision is a simple means of tattoo removal with very acceptable cosmetic results. The technique has several advantages. (1) The depth of skin removal may accurately be controlled as the tattoo pigment is excised with a dermatome. The major portion, if not all of the remaining pigment, is extruded and sloughs with the crust. (2) Scar formation, if it occurs at all, is negligible. (3) No donor site is created. (4) The procedure may be carried out rapidly without admitting patients to hospital, is inexpensive for patients and conserves time for physicians."} {"id": "PMID:1266214", "title": "Neurological complications of endocarditis in persons taking drugs intravenously.", "content": "A study was made of 46 cases of endocarditis in persons known to take drugs intravenously. Findings included significantly lower ages for those patients in whom infections were right-sided. The neurological complication rate was 39 percent overall and 58 percent in the left-sided group. Neurological complications are unusual in right-sided infection. In about a third of those with neurological complications there were sensorial changes without focal signs. Despite a high mortality, neurological complications in Group D streptococcal endocarditis were relatively infrequent. One case is presented in which a foreign body may have contributed to the formation of the embolic material. The clinical and neuropathological features encountered are compared with those reported in persons with endocarditis who were not addicts. The review indicates that neurological complications in nonaddicts and in addicts are similar in type but are more common and severe in addicts.", "contents": "Neurological complications of endocarditis in persons taking drugs intravenously. A study was made of 46 cases of endocarditis in persons known to take drugs intravenously. Findings included significantly lower ages for those patients in whom infections were right-sided. The neurological complication rate was 39 percent overall and 58 percent in the left-sided group. Neurological complications are unusual in right-sided infection. In about a third of those with neurological complications there were sensorial changes without focal signs. Despite a high mortality, neurological complications in Group D streptococcal endocarditis were relatively infrequent. One case is presented in which a foreign body may have contributed to the formation of the embolic material. The clinical and neuropathological features encountered are compared with those reported in persons with endocarditis who were not addicts. The review indicates that neurological complications in nonaddicts and in addicts are similar in type but are more common and severe in addicts."} {"id": "PMID:1266215", "title": "Preimplantational ectogenesis. Science and speculation concerning in vitro fertilization and related procedures.", "content": "In recent years, technical advances have made preimplantational ectogenesis (in vitro maturation, fertilization and early embryonic development) more than a theoretical concept. Such procedures hold great promise in medical research. However, despite our newly-acquired skills in tissue culture and microsurgical manipulation, and contrary to many sensational articles in the lay press, it is not likely that preimplantational ectogenesis will soon attain wide clinical use in humans. Adverse societal attitudes, based largely upon moral and ethical dilemmas, will probably combine with still-unresolved technical difficulties to restrict the clinical applications.", "contents": "Preimplantational ectogenesis. Science and speculation concerning in vitro fertilization and related procedures. In recent years, technical advances have made preimplantational ectogenesis (in vitro maturation, fertilization and early embryonic development) more than a theoretical concept. Such procedures hold great promise in medical research. However, despite our newly-acquired skills in tissue culture and microsurgical manipulation, and contrary to many sensational articles in the lay press, it is not likely that preimplantational ectogenesis will soon attain wide clinical use in humans. Adverse societal attitudes, based largely upon moral and ethical dilemmas, will probably combine with still-unresolved technical difficulties to restrict the clinical applications."} {"id": "PMID:1266271", "title": "[Surveillance of pregnancies with placental dysfunction. IV. Significance of biochemical placental values].", "content": "The efficacy of four different methods for detection of placental dysfunction has been compared in 265 risk pregnancies. The test were urinary oestriol, urinary pregnanediol, activity of human placental lactogen and heat-stable alkaline phosphatase in the serum. It was concluded that best results were obtained by simultaneous use of urinary oestriol und human-placental-lactogen activity. Early detection of placental dysfunction by urinary pregnanediol and heat-stable alkaline phophatase in the serum were rather exceptional.", "contents": "[Surveillance of pregnancies with placental dysfunction. IV. Significance of biochemical placental values]. The efficacy of four different methods for detection of placental dysfunction has been compared in 265 risk pregnancies. The test were urinary oestriol, urinary pregnanediol, activity of human placental lactogen and heat-stable alkaline phosphatase in the serum. It was concluded that best results were obtained by simultaneous use of urinary oestriol und human-placental-lactogen activity. Early detection of placental dysfunction by urinary pregnanediol and heat-stable alkaline phophatase in the serum were rather exceptional."} {"id": "PMID:1266272", "title": "[Surveillance of pregnancies with placental dysfunction. V. Time of the appearance of suspected and pathological values during surveillance methods].", "content": "The results of oestriol excretion, HPL activity and fetal heart rate monitoring are presented during the last three weeks before the birth or the intrauterine fetal death. Abnormal results were found in all cases at least two weeks before the intrauterine death. In the same periode, we observed a raise of abnormal values in cases with intrauterine growth-retardation. In cases with normal birth weight, the majority of values were normal and without a significant decrease.", "contents": "[Surveillance of pregnancies with placental dysfunction. V. Time of the appearance of suspected and pathological values during surveillance methods]. The results of oestriol excretion, HPL activity and fetal heart rate monitoring are presented during the last three weeks before the birth or the intrauterine fetal death. Abnormal results were found in all cases at least two weeks before the intrauterine death. In the same periode, we observed a raise of abnormal values in cases with intrauterine growth-retardation. In cases with normal birth weight, the majority of values were normal and without a significant decrease."} {"id": "PMID:1266273", "title": "[The pattern of distribution of free amino acids in human amniotic fluid related to the duration of pregnancy. Part I: Changes in concentration in normal pregnancy (author's transl)].", "content": "Gas-chromatographic measurement of 18 free amino-acids from about 500 specimens of amniotic fluid between the 10th and 41st week of pregnancy. Statistical methods showed different concentrations of amino-acids in amniotic fluid during pregnancy. Serine, cysteine, methionine and tryptophane show constant concentration. Valine tyrosine and hydroxyproline continuously decrease. The other amino acids tested here show a biphasic course of concentration, falling by about 40-70% between the 10th and the 30th week after which they remain stable. Alanin, threonine, glycine and ornithine show a clear increase of concentration. This diversity of concentration of amino-acids during pregnancy hints at the importance of various factors for the composition of amniotic fluid.", "contents": "[The pattern of distribution of free amino acids in human amniotic fluid related to the duration of pregnancy. Part I: Changes in concentration in normal pregnancy (author's transl)]. Gas-chromatographic measurement of 18 free amino-acids from about 500 specimens of amniotic fluid between the 10th and 41st week of pregnancy. Statistical methods showed different concentrations of amino-acids in amniotic fluid during pregnancy. Serine, cysteine, methionine and tryptophane show constant concentration. Valine tyrosine and hydroxyproline continuously decrease. The other amino acids tested here show a biphasic course of concentration, falling by about 40-70% between the 10th and the 30th week after which they remain stable. Alanin, threonine, glycine and ornithine show a clear increase of concentration. This diversity of concentration of amino-acids during pregnancy hints at the importance of various factors for the composition of amniotic fluid."} {"id": "PMID:1266274", "title": "The flow resistance of the maternal placental vascular bed of anesthetized guinea pigs.", "content": "In anesthetized guinea pigs, the maternal placental vascular bed (the spiral arteries and the trophoblastic lacunae with the draining veins) was perfused with blood via a tube connecting a carotid artery and a spiral artery. The placental blood flow and the blood pressures at the beginning of the perfused spiral artery, in the peripheral part of a nonperfused spiral artery and in the placental vein were measured. From these data the vascular resistance of the maternal vascular bed was calculated to be only 0.8 mm Hg min/ml. A driving pressure of about 10 mm Hg maintains the probably normal placental blood flow. The vascular resistance was found to be independent of the blood pressure and the blood flow.", "contents": "The flow resistance of the maternal placental vascular bed of anesthetized guinea pigs. In anesthetized guinea pigs, the maternal placental vascular bed (the spiral arteries and the trophoblastic lacunae with the draining veins) was perfused with blood via a tube connecting a carotid artery and a spiral artery. The placental blood flow and the blood pressures at the beginning of the perfused spiral artery, in the peripheral part of a nonperfused spiral artery and in the placental vein were measured. From these data the vascular resistance of the maternal vascular bed was calculated to be only 0.8 mm Hg min/ml. A driving pressure of about 10 mm Hg maintains the probably normal placental blood flow. The vascular resistance was found to be independent of the blood pressure and the blood flow."} {"id": "PMID:1266275", "title": "[The villous trophoblast in placentae of premature births (author's transl)].", "content": "Enzyme histochemical behavier (cryostat-and semi-thin slice techniques) of the villous epithelium of 109 \"genuine\" premature birth permits evaluation of a qualitative disturbance of trophoblasts. It is characterised by an increase of pre-degenerative plasmodium and multilocular emergence of highly differentiated or degenerated Langhans cells which lack the potential for plasmodial transformation and thus for regeneration of trophoblasts. The importance of such changes for metabolic competence and hormone synthesis and the link between prematurity and insuficiency of the placenta are discussed.", "contents": "[The villous trophoblast in placentae of premature births (author's transl)]. Enzyme histochemical behavier (cryostat-and semi-thin slice techniques) of the villous epithelium of 109 \"genuine\" premature birth permits evaluation of a qualitative disturbance of trophoblasts. It is characterised by an increase of pre-degenerative plasmodium and multilocular emergence of highly differentiated or degenerated Langhans cells which lack the potential for plasmodial transformation and thus for regeneration of trophoblasts. The importance of such changes for metabolic competence and hormone synthesis and the link between prematurity and insuficiency of the placenta are discussed."} {"id": "PMID:1266276", "title": "[The effect of contrast medium injection into the left ventricle on systolic and diastolic ventricle function].", "content": "The influence of contrast medium on systolic and diastolic left ventricular function was studied in eight patients with coronary heart disease and in five dogs during and five minutes after ventriculography. Two biplane ventriculograms were performed in 5-minute intervals, in the dogs an additional one after 10 minutes. 0.66 cc/kg BW of sodium methyl-glucamin-iothalamate were injected during diastole into the left ventricel. 1. During ventriculography there are only slight changes of left ventricular volumes, pressures and diastolic compliance. The first four opacified heart cycles can be evaluated for the analysis of left ventricular function. 2. In patients with coronary heart disease there are much more pronounced alterations of systolic ventricular function 5 minutes after Ventriculography than in the normal dog. The ischemic ventricle has a reduced tolerance for volume load and negative inotropic effect of contrast media. In patients and dogs diastolic compliance is significantly increased 5 minutes after the injection of contrast medium. After 10 minutes however in the dogs compliance is significantly decreased. Analysing left ventricular function by repeated ventriculographies one has to take into account that the function is altered by the first angiogram. The degree of the changes depends on the initial hemodynamic conditions and on the time interval between the ventriculograms.", "contents": "[The effect of contrast medium injection into the left ventricle on systolic and diastolic ventricle function]. The influence of contrast medium on systolic and diastolic left ventricular function was studied in eight patients with coronary heart disease and in five dogs during and five minutes after ventriculography. Two biplane ventriculograms were performed in 5-minute intervals, in the dogs an additional one after 10 minutes. 0.66 cc/kg BW of sodium methyl-glucamin-iothalamate were injected during diastole into the left ventricel. 1. During ventriculography there are only slight changes of left ventricular volumes, pressures and diastolic compliance. The first four opacified heart cycles can be evaluated for the analysis of left ventricular function. 2. In patients with coronary heart disease there are much more pronounced alterations of systolic ventricular function 5 minutes after Ventriculography than in the normal dog. The ischemic ventricle has a reduced tolerance for volume load and negative inotropic effect of contrast media. In patients and dogs diastolic compliance is significantly increased 5 minutes after the injection of contrast medium. After 10 minutes however in the dogs compliance is significantly decreased. Analysing left ventricular function by repeated ventriculographies one has to take into account that the function is altered by the first angiogram. The degree of the changes depends on the initial hemodynamic conditions and on the time interval between the ventriculograms."} {"id": "PMID:1266277", "title": "[Effect of tricyclic antidepressive agents on hemodynamics and plasms norepinephrine level in man during rest and exertion].", "content": "The effects of i.v. injected antidepressants Imipramine (Tofranil, Geigy) and Dimetacrine (Istonil, Siegfried) on cardiavascular functions were investigated in 18 patients at diagnostic cardiac catheterization. 4 patients were additionally studied during ergometric exercise before and 45 min. after application of both thymoleptica. Determinations of noradrenaline plasma concentrations were carried out in 8 patients. The results show of 25 mg (= 22,1 mg free base) Imipramine or 33.5 mg (= 21.4 mg free base) Dimetacrine did not induce significant changes in heart rate and cardiac index. 2. Already 15 min. after application of both drugs a clear increase in left ventricular end-diastolic pressure (LVEP) was observed. Maximal increase in LVEP - in mean, 26% after Imipramine (p less than 0.0005) and 40% after Dimetacrine (p less than 0.05) - was reached 30-45 min, after injection. 3. A simultaneous increase in mean systemic arterial pressure was related to a marked increase in noradrenaline plasma concentration in all 8 investigated patients. 4. After application of tricyclic antidepressant a larger increase in pulmonary arterial enddiastolic pressure was observed during ergometric exercise.", "contents": "[Effect of tricyclic antidepressive agents on hemodynamics and plasms norepinephrine level in man during rest and exertion]. The effects of i.v. injected antidepressants Imipramine (Tofranil, Geigy) and Dimetacrine (Istonil, Siegfried) on cardiavascular functions were investigated in 18 patients at diagnostic cardiac catheterization. 4 patients were additionally studied during ergometric exercise before and 45 min. after application of both thymoleptica. Determinations of noradrenaline plasma concentrations were carried out in 8 patients. The results show of 25 mg (= 22,1 mg free base) Imipramine or 33.5 mg (= 21.4 mg free base) Dimetacrine did not induce significant changes in heart rate and cardiac index. 2. Already 15 min. after application of both drugs a clear increase in left ventricular end-diastolic pressure (LVEP) was observed. Maximal increase in LVEP - in mean, 26% after Imipramine (p less than 0.0005) and 40% after Dimetacrine (p less than 0.05) - was reached 30-45 min, after injection. 3. A simultaneous increase in mean systemic arterial pressure was related to a marked increase in noradrenaline plasma concentration in all 8 investigated patients. 4. After application of tricyclic antidepressant a larger increase in pulmonary arterial enddiastolic pressure was observed during ergometric exercise."} {"id": "PMID:1266278", "title": "[Evaluation of heart function in chronic coronary disease non-invasive methods].", "content": "In 58 patients with a clinical diagnosis of ischemic heart disease the value of Ecg, phonocardiogram, systolic time intervals and derived indices, apex-cardiogram (Acg), and kinetocardiogram (Kcg) in assessment of cardiac function was examined. In 52 patients coronary artery lesions were demonstrated on selective coronary angiograms, in 40 patients dyssynergy was seen on ventriculograms, and in 14 patients a left vencribular aneurysm was diagnosed. Ecg criteria indicated a normal ejection fraction with a sensitivity of 80% and a specificity of 84%, an ejection fraction less than or equal to 30% with a sensitivity of 72% and a specificity of 77%, a localized dyssynergy with a sensitivity and a specificity of 83% respectively, and a ventricular aneurysm with a sensitivity of 86% and a specifity of 92%. In respect to the latter diagnosis Q-wave criteria proved superior to ST- and T-alterations. An atrial gallop bore nor relationship to the parameters of cardiac function. A protodiastolic gallop proved to be a relative specific but insensitive sign of poor ventricular function. In the majority of cases the corrected injection time was diminished in respect to normal values; a moderate correlation was to be calculated between its shortening and the ejection fraction (r = -0.50). The quotient ejection time divided by preejection period allowed the estimation of an ejection fraction below 30% in 64% of cases without false positive results. There was a close correlation between this quotient and the ejection in the pathologic range below 50% (r = -0.69), whereas no correlation was to be found in the normal range of EF. An Acg could be obtained only in 72% of the patients. A moderate correlation was established to the left ventricular enddiastolic pressure (r = 0.42). The diagnostic score was poor in respect to ventricular aneurysms, which could be recognized in 43%, but were falsely assumed in 40%. Kcg records yielded relatively specific but insensitive indications of a normal fraction (specificity 84%, sensitivity 32%) and of an elevated left ventricular enddiastolic pressure (sensitivity 54%, specificity 80%). Large non-contractile ventricular segments and ventricular aneurysms were recognized with a sensitivity of 72% each and a specificity of 62% and 52% respectively. Multiple regression analysis between various non-invasive methods and hemodynamic data resulted in a closer correlation, but nontheless no exact prediction of the \"true\" values was possible in the single case. It is concluded that the accuracy of the parameters of the non-invasive methods under study in assessing left ventricular performance in coronary heart disease is worse than generally accepted giving reliable information only in patients with very poor and with excellent cardiac function.", "contents": "[Evaluation of heart function in chronic coronary disease non-invasive methods]. In 58 patients with a clinical diagnosis of ischemic heart disease the value of Ecg, phonocardiogram, systolic time intervals and derived indices, apex-cardiogram (Acg), and kinetocardiogram (Kcg) in assessment of cardiac function was examined. In 52 patients coronary artery lesions were demonstrated on selective coronary angiograms, in 40 patients dyssynergy was seen on ventriculograms, and in 14 patients a left vencribular aneurysm was diagnosed. Ecg criteria indicated a normal ejection fraction with a sensitivity of 80% and a specificity of 84%, an ejection fraction less than or equal to 30% with a sensitivity of 72% and a specificity of 77%, a localized dyssynergy with a sensitivity and a specificity of 83% respectively, and a ventricular aneurysm with a sensitivity of 86% and a specifity of 92%. In respect to the latter diagnosis Q-wave criteria proved superior to ST- and T-alterations. An atrial gallop bore nor relationship to the parameters of cardiac function. A protodiastolic gallop proved to be a relative specific but insensitive sign of poor ventricular function. In the majority of cases the corrected injection time was diminished in respect to normal values; a moderate correlation was to be calculated between its shortening and the ejection fraction (r = -0.50). The quotient ejection time divided by preejection period allowed the estimation of an ejection fraction below 30% in 64% of cases without false positive results. There was a close correlation between this quotient and the ejection in the pathologic range below 50% (r = -0.69), whereas no correlation was to be found in the normal range of EF. An Acg could be obtained only in 72% of the patients. A moderate correlation was established to the left ventricular enddiastolic pressure (r = 0.42). The diagnostic score was poor in respect to ventricular aneurysms, which could be recognized in 43%, but were falsely assumed in 40%. Kcg records yielded relatively specific but insensitive indications of a normal fraction (specificity 84%, sensitivity 32%) and of an elevated left ventricular enddiastolic pressure (sensitivity 54%, specificity 80%). Large non-contractile ventricular segments and ventricular aneurysms were recognized with a sensitivity of 72% each and a specificity of 62% and 52% respectively. Multiple regression analysis between various non-invasive methods and hemodynamic data resulted in a closer correlation, but nontheless no exact prediction of the \"true\" values was possible in the single case. It is concluded that the accuracy of the parameters of the non-invasive methods under study in assessing left ventricular performance in coronary heart disease is worse than generally accepted giving reliable information only in patients with very poor and with excellent cardiac function."} {"id": "PMID:1266279", "title": "[Primary pulmonary hypertension and abnormalities of pulmonary arteries].", "content": "Case report of a 5 year old boy with a well diagnosed primary pulmonary hypertension, combined with anomalies of the pulmonary arteries of the left upper lobe of the lungs with angiographically loopy appearance. Congenital heart and vascular disease did not exist; AV-fistulae were not found. There is no proof of a connection between the anomalies of the pulmonary arteries and pulmonary hypertension. There was no similar case in the current literature to be found.", "contents": "[Primary pulmonary hypertension and abnormalities of pulmonary arteries]. Case report of a 5 year old boy with a well diagnosed primary pulmonary hypertension, combined with anomalies of the pulmonary arteries of the left upper lobe of the lungs with angiographically loopy appearance. Congenital heart and vascular disease did not exist; AV-fistulae were not found. There is no proof of a connection between the anomalies of the pulmonary arteries and pulmonary hypertension. There was no similar case in the current literature to be found."} {"id": "PMID:1266280", "title": "[Removal of catheter fragments from the heart and central venous vascular sections].", "content": "The floating catheter technique is much more frequently used than before. So far, relatively rare complications become of practical importance. A report is given on three cases in which catheter fragments were cut off and floated into the right heart or pulmonary artery. In one case, the fragment was removed from the right heart after percutaneous insertion of a specially devised instrument similar to a myocardial bioptome. The question does not seem to be settled as yet, whether or not surgical interventions are indicated, when a fragment cannot be removed by these techniques.", "contents": "[Removal of catheter fragments from the heart and central venous vascular sections]. The floating catheter technique is much more frequently used than before. So far, relatively rare complications become of practical importance. A report is given on three cases in which catheter fragments were cut off and floated into the right heart or pulmonary artery. In one case, the fragment was removed from the right heart after percutaneous insertion of a specially devised instrument similar to a myocardial bioptome. The question does not seem to be settled as yet, whether or not surgical interventions are indicated, when a fragment cannot be removed by these techniques."} {"id": "PMID:1266281", "title": "[Aortic abnormalities in Marfan's syndrome].", "content": "Three different forms of aortic lesions in Marfan's Syndrome are demonstrated: 1. moderately severe aortic valve insufficiency due to sinus of Valsalva aneurysm; 2. severe aortic valve insufficiency due to aneurysmal widening of the ascending aorta; 3. an unusually wide dissecting aneurysm extending from the aortic root to the aortic bifurcation. A review of the current literature of the changes in Marfan's Syndrome is given. It is obvious that early diagnosis of the cardiovascular changes is important for the patient's prognosis, allowing the optimal time for surgical intervention to be chosen.", "contents": "[Aortic abnormalities in Marfan's syndrome]. Three different forms of aortic lesions in Marfan's Syndrome are demonstrated: 1. moderately severe aortic valve insufficiency due to sinus of Valsalva aneurysm; 2. severe aortic valve insufficiency due to aneurysmal widening of the ascending aorta; 3. an unusually wide dissecting aneurysm extending from the aortic root to the aortic bifurcation. A review of the current literature of the changes in Marfan's Syndrome is given. It is obvious that early diagnosis of the cardiovascular changes is important for the patient's prognosis, allowing the optimal time for surgical intervention to be chosen."} {"id": "PMID:1266282", "title": "[Corrected transposition of great vessels in adult age].", "content": "Two adult cases of corrected transposition of the great arteries are presented. One of the two males had associated ventricular septal defect, the other one presented as an isolated anomaly. The characteristic clinical features are: loud second heart sound with audible pulmonic component of the left sternal border in the absence of pulmonary hypertension. Abnormal precordial impulse upon palpation. Chest X-ray shows absence of pulmonic segment and of the aortic knob with the contour of the ascending aorta to the left of the mediastinum. Ecg anomalies may be multiple; typically anomalous septal Q-waves are consistently absent. Corrected transposition is well tolerated even into adulthood. Prognosis is dominated by assiciated anomalies.", "contents": "[Corrected transposition of great vessels in adult age]. Two adult cases of corrected transposition of the great arteries are presented. One of the two males had associated ventricular septal defect, the other one presented as an isolated anomaly. The characteristic clinical features are: loud second heart sound with audible pulmonic component of the left sternal border in the absence of pulmonary hypertension. Abnormal precordial impulse upon palpation. Chest X-ray shows absence of pulmonic segment and of the aortic knob with the contour of the ascending aorta to the left of the mediastinum. Ecg anomalies may be multiple; typically anomalous septal Q-waves are consistently absent. Corrected transposition is well tolerated even into adulthood. Prognosis is dominated by assiciated anomalies."} {"id": "PMID:1266283", "title": "The effect of pentoxifylline on central and peripheral haemodynamics--an experimental clinical study.", "content": "The effect of an i.v. injection of 100 mg pentoxifylline on cardiac output, stroke volume, heart rate, atrial pressure, pulmonary arterial, pulmonary capillary and aortic pressure in normal myocardial function and in myocardial insufficiency was investigated in 8 patients with peripheral-arterial occlusive disorders. In normal myocardial function there was a brief, statistically significant increase in cardiac output of +9.6% and a simultaneous reduction in total peripheral resistance of -7.6%. No increase in cardiac output was recorded in patients with myocardial insufficiency. None of the other parameters monitored showed any statistically significant change.", "contents": "The effect of pentoxifylline on central and peripheral haemodynamics--an experimental clinical study. The effect of an i.v. injection of 100 mg pentoxifylline on cardiac output, stroke volume, heart rate, atrial pressure, pulmonary arterial, pulmonary capillary and aortic pressure in normal myocardial function and in myocardial insufficiency was investigated in 8 patients with peripheral-arterial occlusive disorders. In normal myocardial function there was a brief, statistically significant increase in cardiac output of +9.6% and a simultaneous reduction in total peripheral resistance of -7.6%. No increase in cardiac output was recorded in patients with myocardial insufficiency. None of the other parameters monitored showed any statistically significant change."} {"id": "PMID:1266284", "title": "Effect of malnutrition on susceptibility of mice to Trypanosoma musculi: vitamin A-deficiency.", "content": "Vitamin A-deficiency was studied in mice infected with Trypanosoma musculi. Irrespective of diet, trypomastigotes (trypanosomes) appeared in peripheral tail blood of all inoculated mice after 6-day incubation periods. On the average, vitamin A-deficient mice had parasitemias about 10 times greater than animals fed a complete diet and 8 times pair-fed controls. Parasitemias lasted longer in vitamin-deficient hosts, and reached a maximum five days later than those from control hosts.", "contents": "Effect of malnutrition on susceptibility of mice to Trypanosoma musculi: vitamin A-deficiency. Vitamin A-deficiency was studied in mice infected with Trypanosoma musculi. Irrespective of diet, trypomastigotes (trypanosomes) appeared in peripheral tail blood of all inoculated mice after 6-day incubation periods. On the average, vitamin A-deficient mice had parasitemias about 10 times greater than animals fed a complete diet and 8 times pair-fed controls. Parasitemias lasted longer in vitamin-deficient hosts, and reached a maximum five days later than those from control hosts."} {"id": "PMID:1266286", "title": "The fine structure of the endogenous stages of Eimeria labbeana. 3. Feeding Organelles.", "content": "The fine structure of the feeding organelles of the endogenous developmental stages of Eimeria labbeana from the ileal mucosa of the common Pigeon, Columba livia, is described and compared with similar structures of other species of Eimeria. Intra-cytoplasmic, membrane-bound vesicles of varying shapes and dimensions, and pinocytotic vesicle, were seen in association with cup-shaped or v-shaped invaginations in early schizonts, early macrogamonts, and macrogametes. Deep invaginations, averaging 1.7 x 0.5 mu in size, and found on the surface of early schizonts, early and young macrogamonts, and developing microgamonts, apparently function as organelles of ingestion and breakdown of host-cell cytoplasm. Micropores were rarely seen in schizonts and never in microgametes. The merozoite had one typical micropore (850 x 680 A) and a number of micropore-like invaginations. Micropores of the microgamonts averaged 610 x 580A, and those of macrogamonts and macrogametes averaged 1,220 x 780 A. A typical micropore was observed in an early oocyst. Intravacuolar tubules, each 580 A in diameter and composed of nine microtubule-like subunits, were observed only in about 1 per cent of the more than 4,000 macrogametes studied. This paper establishes that E. labbeana is a species that possesses all the known organelles associated with feeding, expect the intravacuolar folds.", "contents": "The fine structure of the endogenous stages of Eimeria labbeana. 3. Feeding Organelles. The fine structure of the feeding organelles of the endogenous developmental stages of Eimeria labbeana from the ileal mucosa of the common Pigeon, Columba livia, is described and compared with similar structures of other species of Eimeria. Intra-cytoplasmic, membrane-bound vesicles of varying shapes and dimensions, and pinocytotic vesicle, were seen in association with cup-shaped or v-shaped invaginations in early schizonts, early macrogamonts, and macrogametes. Deep invaginations, averaging 1.7 x 0.5 mu in size, and found on the surface of early schizonts, early and young macrogamonts, and developing microgamonts, apparently function as organelles of ingestion and breakdown of host-cell cytoplasm. Micropores were rarely seen in schizonts and never in microgametes. The merozoite had one typical micropore (850 x 680 A) and a number of micropore-like invaginations. Micropores of the microgamonts averaged 610 x 580A, and those of macrogamonts and macrogametes averaged 1,220 x 780 A. A typical micropore was observed in an early oocyst. Intravacuolar tubules, each 580 A in diameter and composed of nine microtubule-like subunits, were observed only in about 1 per cent of the more than 4,000 macrogametes studied. This paper establishes that E. labbeana is a species that possesses all the known organelles associated with feeding, expect the intravacuolar folds."} {"id": "PMID:1266285", "title": "Effects of immune lymphocyte products and serum antibody on the multiplication of Toxoplasma in murine peritoneal macrophages.", "content": "In vitro studies on cell-mediated immunity against Toxoplasma infection were carried out by estimating the ability of antigenically stimulated lymphocytes. Splenic lymphocytes from normal mice and from hyper-immunized mice were cultured in the presence or absence of Toxoplasma lysate antigen. The cell-free supernatant fluids from the lymphocyte cultures were assassed for their ability to alter the functional capacities of normal macrophages. When glycogen-induced peritoneal macrophages were incubated with the culture supernatant from immune lymphocytes reacting with specific angigen, the intracellular multiplication of the organisms was inhibited remarkably. In contrast, the addition of antitoxoplasma antibody to culture medium had no effect on the enhancement of phagocytic activity of culture macrophages. However, when extra-cellular organisms were exposed to fresh or heat-inactivated immune serum just before infection of the monolayers, the intracellular multiplication of Toxoplasmas was inhibited significantly by either activated or normal macrophages.", "contents": "Effects of immune lymphocyte products and serum antibody on the multiplication of Toxoplasma in murine peritoneal macrophages. In vitro studies on cell-mediated immunity against Toxoplasma infection were carried out by estimating the ability of antigenically stimulated lymphocytes. Splenic lymphocytes from normal mice and from hyper-immunized mice were cultured in the presence or absence of Toxoplasma lysate antigen. The cell-free supernatant fluids from the lymphocyte cultures were assassed for their ability to alter the functional capacities of normal macrophages. When glycogen-induced peritoneal macrophages were incubated with the culture supernatant from immune lymphocytes reacting with specific angigen, the intracellular multiplication of the organisms was inhibited remarkably. In contrast, the addition of antitoxoplasma antibody to culture medium had no effect on the enhancement of phagocytic activity of culture macrophages. However, when extra-cellular organisms were exposed to fresh or heat-inactivated immune serum just before infection of the monolayers, the intracellular multiplication of Toxoplasmas was inhibited significantly by either activated or normal macrophages."} {"id": "PMID:1266287", "title": "Sporozoites of Eimeria acervulina within intestinal macrophages in normal experimental infections: an ultrastructural study.", "content": "Sporozoites of Eimeria acervulina were observed in macrophages of the intestinal epithelium 5 and 6 days post-infection. These sporozoites lay within a well developed parasitophorous vacuole, were normal in structure and showed no signs of development. Macrophages harbouring sporozoites showed considerable structural changes, most pronounced being an absence of lysosomes, an enlarged nucleolus and extensive proliferation of the Golgi complex and endoplasmic reticulum. Possible mechanisms of survival and transport of sporozoites to preferred sites of development are discussed.", "contents": "Sporozoites of Eimeria acervulina within intestinal macrophages in normal experimental infections: an ultrastructural study. Sporozoites of Eimeria acervulina were observed in macrophages of the intestinal epithelium 5 and 6 days post-infection. These sporozoites lay within a well developed parasitophorous vacuole, were normal in structure and showed no signs of development. Macrophages harbouring sporozoites showed considerable structural changes, most pronounced being an absence of lysosomes, an enlarged nucleolus and extensive proliferation of the Golgi complex and endoplasmic reticulum. Possible mechanisms of survival and transport of sporozoites to preferred sites of development are discussed."} {"id": "PMID:1266288", "title": "[Capillaria hepatica infection of Mastomys natalensis: on the development, egg production and host reaction (author's transl)].", "content": "Studies on the development and egg production of Capillaria hepatica and on the macroscopically visible alterations of the liver and spleen of the host were carried out in experimentally infected Mastomys natalensis. Following the oral administration of infective eggs the first stage larvae hatched in the caecum of fasting and fed animals after about 8 and 15 hours respectively. The prepatency could be found with 20 days. The dynamics and duration of egg production of the parasite proved to be dependent on the infective dose. After the first week of patency increasing numbers of eggs/liver were found with increasing doses of infection up to 800 eggs per animal. This relation could not be observed 76 days post infection. After infections with 50, 300 und 800 eggs per animal maximum egg production was found between 60 and 72, 36 and 48 and about 30 days p.i., respectively. The egg production of the parasites correspondently continued for more than 85 days after infection or had ceased 72 or 48 days p.i. Intraperitoneal administration of infective eggs revealed a lower infection rate, evaluated by the number of eggs per liver, than oral infection.", "contents": "[Capillaria hepatica infection of Mastomys natalensis: on the development, egg production and host reaction (author's transl)]. Studies on the development and egg production of Capillaria hepatica and on the macroscopically visible alterations of the liver and spleen of the host were carried out in experimentally infected Mastomys natalensis. Following the oral administration of infective eggs the first stage larvae hatched in the caecum of fasting and fed animals after about 8 and 15 hours respectively. The prepatency could be found with 20 days. The dynamics and duration of egg production of the parasite proved to be dependent on the infective dose. After the first week of patency increasing numbers of eggs/liver were found with increasing doses of infection up to 800 eggs per animal. This relation could not be observed 76 days post infection. After infections with 50, 300 und 800 eggs per animal maximum egg production was found between 60 and 72, 36 and 48 and about 30 days p.i., respectively. The egg production of the parasites correspondently continued for more than 85 days after infection or had ceased 72 or 48 days p.i. Intraperitoneal administration of infective eggs revealed a lower infection rate, evaluated by the number of eggs per liver, than oral infection."} {"id": "PMID:1266289", "title": "[The attachment response of the cercaria of Schistosoma mansoni. Influence of natural substrates and temperature (author's transl)].", "content": "The behaviour of the cercaria, following contact with different animal and human substrates during swimming, has been studied. Four patterns of behavior related to the intensity of stimulation can be distinguished: 1. backward reaction, 2. stopping, 3. forward reaction, 4. attachment (Figs. 2 and 3). Mechanical stimulation of the cercaria by touching or water turbulence, prior to contact with the substrate has an insignificant effect on attachment. Both attachment and the first step in penetration (crawling over the substrate) are stimulated by a rise in temperature (Figs. 4 and 5) and the chemical properties of the substrate. However, the steps in penetration may possibly be stimulated by chemical components and perceived by receptors different from those involved in attachment.", "contents": "[The attachment response of the cercaria of Schistosoma mansoni. Influence of natural substrates and temperature (author's transl)]. The behaviour of the cercaria, following contact with different animal and human substrates during swimming, has been studied. Four patterns of behavior related to the intensity of stimulation can be distinguished: 1. backward reaction, 2. stopping, 3. forward reaction, 4. attachment (Figs. 2 and 3). Mechanical stimulation of the cercaria by touching or water turbulence, prior to contact with the substrate has an insignificant effect on attachment. Both attachment and the first step in penetration (crawling over the substrate) are stimulated by a rise in temperature (Figs. 4 and 5) and the chemical properties of the substrate. However, the steps in penetration may possibly be stimulated by chemical components and perceived by receptors different from those involved in attachment."} {"id": "PMID:1266290", "title": "A technique for in vivo labelling of Fasciola hepatica miracidia with radioselenium.", "content": "Radioactivity is incorporated in Fasciola hepatica and its eggs when 75Semethionine is administered intraperitoneally in chronically infected mice. Maximum egg-bound radioactivity is achieved 2-3 days after the administration of the labelled aminoacid. Seventy-three per cent of the radioactivity of the egg is recovered in the free-swimming miracidium. There appears to be no altered motility or infectivity to snails of miracidia made radioactive at a level corresponding to 6 pCi per larva. Suggestions are made for the application of labelled larvae in studies on various aspects of the parasite-snail contact.", "contents": "A technique for in vivo labelling of Fasciola hepatica miracidia with radioselenium. Radioactivity is incorporated in Fasciola hepatica and its eggs when 75Semethionine is administered intraperitoneally in chronically infected mice. Maximum egg-bound radioactivity is achieved 2-3 days after the administration of the labelled aminoacid. Seventy-three per cent of the radioactivity of the egg is recovered in the free-swimming miracidium. There appears to be no altered motility or infectivity to snails of miracidia made radioactive at a level corresponding to 6 pCi per larva. Suggestions are made for the application of labelled larvae in studies on various aspects of the parasite-snail contact."} {"id": "PMID:1266291", "title": "[Long-term follow-up after arthrodesis of the hip-joint using cross-plates and pelvic osteotomy, particularly late complications. Results of follow-up for 4-8 years (author's transl)].", "content": "In two thirds of our patients there were no complications. All fractures could be healed after osteosynthesis or plaster. At least those patients who had tight pseudarthroses were relatively free from pain on weight-bearing. But 34% of our patients showed severe complications - pseudarthroses and post-operative fractures. The argument in favor of early mobilisation, the mainstay for the choice of this technique of arthrodesis, does not - as our long-term follow-up shows - carry conviction.", "contents": "[Long-term follow-up after arthrodesis of the hip-joint using cross-plates and pelvic osteotomy, particularly late complications. Results of follow-up for 4-8 years (author's transl)]. In two thirds of our patients there were no complications. All fractures could be healed after osteosynthesis or plaster. At least those patients who had tight pseudarthroses were relatively free from pain on weight-bearing. But 34% of our patients showed severe complications - pseudarthroses and post-operative fractures. The argument in favor of early mobilisation, the mainstay for the choice of this technique of arthrodesis, does not - as our long-term follow-up shows - carry conviction."} {"id": "PMID:1266292", "title": "[The prevention of infection for transplantation of frozen allogeneic joints (author's transl)].", "content": "Transplantating 8 hips and three knees the antibiotic prophylaxis was improved. It is demonstrable, that Gentamycin (Refobacin [Merck]), due to its chemical stability and its widespread antibiotic efficiency is the optimal substance if the antibiotical activity in the transplants is induced by an in vivo-treatment of the donor.", "contents": "[The prevention of infection for transplantation of frozen allogeneic joints (author's transl)]. Transplantating 8 hips and three knees the antibiotic prophylaxis was improved. It is demonstrable, that Gentamycin (Refobacin [Merck]), due to its chemical stability and its widespread antibiotic efficiency is the optimal substance if the antibiotical activity in the transplants is induced by an in vivo-treatment of the donor."} {"id": "PMID:1266293", "title": "[Report on a two-year experience with an ultrasterile operatory (author's transl)].", "content": "2,078 orthopaedic operations were carried out. No infections were observed at 640 hip-joint total endoprosthesis, 26 knee-joint endoprosthesis and 185 osteosynthesis. One primary infection happened in one case only, namely at an elbow-joint endoprosthesis. The compressed air installation, which drives the airturbines, was found to be the reason for the air not being germ-free what caused the infection. It is important that the turbines operate with germ-free air, and that the air recycling equipment is air-tight. The germ-free air of the horizontal displacement flow in an ultra-sterile operatory gives optimum ambient conditions for the operations, particularly when alloplastic interventions with big extraneous objects entail the risk of infections. After also many hours of operation, the air germination was extremely low and practically insignificant and cannot be obtained at such a low degree for conventionally air-conditioned operatories.", "contents": "[Report on a two-year experience with an ultrasterile operatory (author's transl)]. 2,078 orthopaedic operations were carried out. No infections were observed at 640 hip-joint total endoprosthesis, 26 knee-joint endoprosthesis and 185 osteosynthesis. One primary infection happened in one case only, namely at an elbow-joint endoprosthesis. The compressed air installation, which drives the airturbines, was found to be the reason for the air not being germ-free what caused the infection. It is important that the turbines operate with germ-free air, and that the air recycling equipment is air-tight. The germ-free air of the horizontal displacement flow in an ultra-sterile operatory gives optimum ambient conditions for the operations, particularly when alloplastic interventions with big extraneous objects entail the risk of infections. After also many hours of operation, the air germination was extremely low and practically insignificant and cannot be obtained at such a low degree for conventionally air-conditioned operatories."} {"id": "PMID:1266294", "title": "[Perthes' disease, caused by initial sybovitis? (author's transl)].", "content": "An important factor in Perthes' disease is the primary affection of the nutritient vessels, though the etiology is unknown. The observation of four cases of painful hip disease with clinical symptoms of coxitis, but roentgenological and biopsy proofed evidence of aseptic necrosis of the epiphysis of the hip, gives reason to postulate the concept of initial synovitis as one of the possible causes of Perthes' disease. This concept is linked to Perthes-like pathology in cases of mediteranean fever with synovitis of the hip due to polyserositis. In the initial phase of the disease therapeutic consequences are antiinflammatory medication and early fluid aspiration from the joint to relief the intraarticular pressure.", "contents": "[Perthes' disease, caused by initial sybovitis? (author's transl)]. An important factor in Perthes' disease is the primary affection of the nutritient vessels, though the etiology is unknown. The observation of four cases of painful hip disease with clinical symptoms of coxitis, but roentgenological and biopsy proofed evidence of aseptic necrosis of the epiphysis of the hip, gives reason to postulate the concept of initial synovitis as one of the possible causes of Perthes' disease. This concept is linked to Perthes-like pathology in cases of mediteranean fever with synovitis of the hip due to polyserositis. In the initial phase of the disease therapeutic consequences are antiinflammatory medication and early fluid aspiration from the joint to relief the intraarticular pressure."} {"id": "PMID:1266296", "title": "[A case of fatigue fracture at the border between tibial head and shaft after removal of a small corticocancellous graft (author's transl)].", "content": "Report on a case. Causes were: 1. faulty technique of removing graft. 2. Osteoporosis due to immobilisation in plaster after several previous operations. 3. functional overloading with mechanical after-treatment. The need for a proper technique of removing the graft - particularly for the operation after Maquet - is once more emphasized.", "contents": "[A case of fatigue fracture at the border between tibial head and shaft after removal of a small corticocancellous graft (author's transl)]. Report on a case. Causes were: 1. faulty technique of removing graft. 2. Osteoporosis due to immobilisation in plaster after several previous operations. 3. functional overloading with mechanical after-treatment. The need for a proper technique of removing the graft - particularly for the operation after Maquet - is once more emphasized."} {"id": "PMID:1266297", "title": "[Tuberculous osteitis of the frontal bone (author's transl)].", "content": "The frontal bone is only rarely the site of tuberculosis. Most patients come from Eastern countries. Report on 2 own cases. Warning against treatment with cortisone derivatives before diagnosis is made and antituberculous treatment given. To culture and animal tests give the best changes. Special sanatoria are suitable for treatment.", "contents": "[Tuberculous osteitis of the frontal bone (author's transl)]. The frontal bone is only rarely the site of tuberculosis. Most patients come from Eastern countries. Report on 2 own cases. Warning against treatment with cortisone derivatives before diagnosis is made and antituberculous treatment given. To culture and animal tests give the best changes. Special sanatoria are suitable for treatment."} {"id": "PMID:1266299", "title": "[About the proposition of strength of animal-experimental results with hip endoprosthesis. A comparative analysis of the stress of the upper thigh of man and of four-leg (author's transl)].", "content": "Precise knowledge of the biomechanic of the hip of man and of animal is necessary to evaluate the procedures of adaption of the femur after endoprosthesis with animal experiment and the transfer into the endoprosthesis of the human medicine. After functional-morphological and biomechanical researches (Pauwels), the upper femoral end of the man is highly stressed by bending at direct level while lowly stressed at sagittal level. The present own biomechanical analysis of the hip of the dog reveal - under consideration of the gaits \"pace\", \"trot\" and \"gallop\" - that the coxal end of the femur of the four-leg compared with that of man is highly stressed by bending at sagittal level as well as at direct level. The observations are herewith clearly explained that intense reconstructions of the bone at artificial human thighs are found mainly at lateral and medial circumference of the bed of the prosthesis, at animal experiment however at dorsal, ventral as well as medial circumference.", "contents": "[About the proposition of strength of animal-experimental results with hip endoprosthesis. A comparative analysis of the stress of the upper thigh of man and of four-leg (author's transl)]. Precise knowledge of the biomechanic of the hip of man and of animal is necessary to evaluate the procedures of adaption of the femur after endoprosthesis with animal experiment and the transfer into the endoprosthesis of the human medicine. After functional-morphological and biomechanical researches (Pauwels), the upper femoral end of the man is highly stressed by bending at direct level while lowly stressed at sagittal level. The present own biomechanical analysis of the hip of the dog reveal - under consideration of the gaits \"pace\", \"trot\" and \"gallop\" - that the coxal end of the femur of the four-leg compared with that of man is highly stressed by bending at sagittal level as well as at direct level. The observations are herewith clearly explained that intense reconstructions of the bone at artificial human thighs are found mainly at lateral and medial circumference of the bed of the prosthesis, at animal experiment however at dorsal, ventral as well as medial circumference."} {"id": "PMID:1266300", "title": "[High tibial osteotomy--fixation by means of external fixation--indication, technique, complications (author's transl)].", "content": "High tibial osteotomy has proved its value in the treatment of gonarthrosis with or without axis deformity. The thrust of weight-bearing and other stresses is lessened on the degenerated tibial condyle and transferred to the more normal condyle. The stable fixation by means of external fixation allows early movement of the knee joint.-R-ferences to operative technique, indication, complications and after-treatment.", "contents": "[High tibial osteotomy--fixation by means of external fixation--indication, technique, complications (author's transl)]. High tibial osteotomy has proved its value in the treatment of gonarthrosis with or without axis deformity. The thrust of weight-bearing and other stresses is lessened on the degenerated tibial condyle and transferred to the more normal condyle. The stable fixation by means of external fixation allows early movement of the knee joint.-R-ferences to operative technique, indication, complications and after-treatment."} {"id": "PMID:1266301", "title": "[Electromyographic study of movements in infants with cerebral palsy (author's transl)].", "content": "In 43 infants between 3 and 16 months old electromyographic studies were performed by recording movement patterns. Surface electrodes were fixed to the legs, recording the activities of adductors, small gluteal muscles, M. rectus and hamstrings. The impulses were fed into the computer. Synergistic and antagonistic muscles were compared by correlation analysis. Certain movement patterns were provoked by turning the infants from supine to the sides, pulling up to sitting, tilting sideways, vertical hanging and standing. Synergistic and antagonistic muscle groups were compared by correlation anaysis. Significant differences in motor behavior were shown to exist between spastic and healthy infants: The spastic infants showed widely spread synchronous innervations. Besides, comparison of mean activity values exposed a significant preponderance of mean activity values exposed a significant preponderance of adductor activity to gluteal activity in spastic infants. - In qualitative analysis by a rating system diagnostic differentiation of individual cases was possible. This proved of special value in infants with postural asymmetries or abnormal musculatur tone.", "contents": "[Electromyographic study of movements in infants with cerebral palsy (author's transl)]. In 43 infants between 3 and 16 months old electromyographic studies were performed by recording movement patterns. Surface electrodes were fixed to the legs, recording the activities of adductors, small gluteal muscles, M. rectus and hamstrings. The impulses were fed into the computer. Synergistic and antagonistic muscles were compared by correlation analysis. Certain movement patterns were provoked by turning the infants from supine to the sides, pulling up to sitting, tilting sideways, vertical hanging and standing. Synergistic and antagonistic muscle groups were compared by correlation anaysis. Significant differences in motor behavior were shown to exist between spastic and healthy infants: The spastic infants showed widely spread synchronous innervations. Besides, comparison of mean activity values exposed a significant preponderance of mean activity values exposed a significant preponderance of adductor activity to gluteal activity in spastic infants. - In qualitative analysis by a rating system diagnostic differentiation of individual cases was possible. This proved of special value in infants with postural asymmetries or abnormal musculatur tone."} {"id": "PMID:1266302", "title": "[Electron microscopic examinations on foam cells in pigmented villonodular synovitis (PVS) (author's transl)].", "content": "The pathologic and histologic features of 17 cases of pigmented villonodular synovitis and bursitis are described. Similar lesions were induced in rabbit knee joints by injection of hypercholesterolaemic serum. A therory is presented that the inflammatory reaction is induced by release of cholesterol esters and crystals from foam cells in a manner similar to crystal-induced synovitis. It is theorized that a disturbance of cholesterol metabolism is responsible for the development of foam cells.", "contents": "[Electron microscopic examinations on foam cells in pigmented villonodular synovitis (PVS) (author's transl)]. The pathologic and histologic features of 17 cases of pigmented villonodular synovitis and bursitis are described. Similar lesions were induced in rabbit knee joints by injection of hypercholesterolaemic serum. A therory is presented that the inflammatory reaction is induced by release of cholesterol esters and crystals from foam cells in a manner similar to crystal-induced synovitis. It is theorized that a disturbance of cholesterol metabolism is responsible for the development of foam cells."} {"id": "PMID:1266303", "title": "[Perthe's disease, results of conservative treatment (author's transl)].", "content": "After a survey of causation, symptoms and therapy of Perthe's disease, clinical and radiographic findings of 62 children treated conservatively are described. For evaluation the \"plumpness quotient\" is introduced, in addition to the known radius-, joint-surface- and epiphysus quotients, as a measure of deformity of head and neck of femur. Besides consequential avoidance of weight-bearing, age, length of history and first radiologic findings are of decisive importance. The results of conservative treatment are no worse than those of surgery.", "contents": "[Perthe's disease, results of conservative treatment (author's transl)]. After a survey of causation, symptoms and therapy of Perthe's disease, clinical and radiographic findings of 62 children treated conservatively are described. For evaluation the \"plumpness quotient\" is introduced, in addition to the known radius-, joint-surface- and epiphysus quotients, as a measure of deformity of head and neck of femur. Besides consequential avoidance of weight-bearing, age, length of history and first radiologic findings are of decisive importance. The results of conservative treatment are no worse than those of surgery."} {"id": "PMID:1266304", "title": "[Spontaneous stiffness of the hip-joint in puberty (author's transl)].", "content": "This condition has been described by the author in 1952. Here a further 12 cases are reported. The condition arises as a consequence of increased prepubertal growth and consequent compression between head of femur and acetabulum. Narrowing of the joint space can be treated by decompressing surgery on muscles. The author belives that such treatment of the less affected side as well serves prevention of arthorosis.", "contents": "[Spontaneous stiffness of the hip-joint in puberty (author's transl)]. This condition has been described by the author in 1952. Here a further 12 cases are reported. The condition arises as a consequence of increased prepubertal growth and consequent compression between head of femur and acetabulum. Narrowing of the joint space can be treated by decompressing surgery on muscles. The author belives that such treatment of the less affected side as well serves prevention of arthorosis."} {"id": "PMID:1266305", "title": "[Operative treatment of recurrent dislocation of the patella by Br\u00fcckner (author's transl)].", "content": "It is reported on the experiences of 43 patients, which surgery was performed on because of recurrent dislocation of the patella. In all these cases we applied the restraining operation by Br\u00fcckner. The advantage of this method is the earlier training without a cast. The operative method and the postoperative training are explained. Until now recidives were not discovered.", "contents": "[Operative treatment of recurrent dislocation of the patella by Br\u00fcckner (author's transl)]. It is reported on the experiences of 43 patients, which surgery was performed on because of recurrent dislocation of the patella. In all these cases we applied the restraining operation by Br\u00fcckner. The advantage of this method is the earlier training without a cast. The operative method and the postoperative training are explained. Until now recidives were not discovered."} {"id": "PMID:1266306", "title": "[The involvement of the position of the femoral head through intertrochanteric osteotomies (author's transl)].", "content": "The definition of capacity and strain of the hip joint has since Pauwels (1965 and 1973) been examined and quantitative and qualitative described by various authors. In the following it is attempted to state the relations between intertrochanter correction and the position of the hip joint, which enable a declaration on the dislocation of the main carrying zone of the head of femur. Factors and methods being complementary and such having an effect of contrary sence are thereat especially described.", "contents": "[The involvement of the position of the femoral head through intertrochanteric osteotomies (author's transl)]. The definition of capacity and strain of the hip joint has since Pauwels (1965 and 1973) been examined and quantitative and qualitative described by various authors. In the following it is attempted to state the relations between intertrochanter correction and the position of the hip joint, which enable a declaration on the dislocation of the main carrying zone of the head of femur. Factors and methods being complementary and such having an effect of contrary sence are thereat especially described."} {"id": "PMID:1266307", "title": "[Investigations of polymethylmetacrylate for replacement of small joints (author's transl)].", "content": "Swelling, monomer production, polymerization and frictional qualities of test samples of Palocos E, Palacos R and Paladon 65 (Messrs Kulzer & Co, Bad Homburg) have been examined in order to establish which of these plastic substances would be most suitable for replacement of small joints. We found that samples of Palacos E, hardened under pressure of 3.0 kp, had the most favorable qualities.", "contents": "[Investigations of polymethylmetacrylate for replacement of small joints (author's transl)]. Swelling, monomer production, polymerization and frictional qualities of test samples of Palocos E, Palacos R and Paladon 65 (Messrs Kulzer & Co, Bad Homburg) have been examined in order to establish which of these plastic substances would be most suitable for replacement of small joints. We found that samples of Palacos E, hardened under pressure of 3.0 kp, had the most favorable qualities."} {"id": "PMID:1266308", "title": "[The synovial pump of the knee-joint (author's transl)].", "content": "Survey of basic principles of movement of the knee-joint and anatomical description of the synovial cavity. Description of active production of synovia. The \"synovial pump\" of the knee-joint is made possible by the stability of the volume in the joint.", "contents": "[The synovial pump of the knee-joint (author's transl)]. Survey of basic principles of movement of the knee-joint and anatomical description of the synovial cavity. Description of active production of synovia. The \"synovial pump\" of the knee-joint is made possible by the stability of the volume in the joint."} {"id": "PMID:1266309", "title": "[Derivation and analyses of neuro signals from the periphery nerv system for a multi channelled prothesis (author's transl)].", "content": "This publications shows new ways of prosthesis controlled by nerv action potentials. We introduce results of neurophysiological trials on animals which will be the basis for a neuroelectric prosthesis for human beings.", "contents": "[Derivation and analyses of neuro signals from the periphery nerv system for a multi channelled prothesis (author's transl)]. This publications shows new ways of prosthesis controlled by nerv action potentials. We introduce results of neurophysiological trials on animals which will be the basis for a neuroelectric prosthesis for human beings."} {"id": "PMID:1266414", "title": "[PR-Toxin-production of Penicillium roqueforti-Strains (author's transl)].", "content": "One blue-type cheese starter and 11 isolates of P. roqueforti from different foodstuffs were tested for the production of PR-toxin. 3 strains were able to produce the toxin on rice at 15 degrees C and sometimes at 30 degrees C. The toxin quantities detected were 310-960 ppb. The starter culture didn't produce any PR-toxin. The investigations with P. roqueforti NRRL 849 showed a toxin-production in the temperature range of 15-30 degrees C, with an optimum at 15 degrees C, whereas 25 degrees C was the optimum for growth. PR-toxin was determined by thin-layer-chromatography and in doubtful cases by mass-spectrometry.", "contents": "[PR-Toxin-production of Penicillium roqueforti-Strains (author's transl)]. One blue-type cheese starter and 11 isolates of P. roqueforti from different foodstuffs were tested for the production of PR-toxin. 3 strains were able to produce the toxin on rice at 15 degrees C and sometimes at 30 degrees C. The toxin quantities detected were 310-960 ppb. The starter culture didn't produce any PR-toxin. The investigations with P. roqueforti NRRL 849 showed a toxin-production in the temperature range of 15-30 degrees C, with an optimum at 15 degrees C, whereas 25 degrees C was the optimum for growth. PR-toxin was determined by thin-layer-chromatography and in doubtful cases by mass-spectrometry."} {"id": "PMID:1266415", "title": "L-malate in golden delicious apples as a possible parameter of acceptability.", "content": "Several batches of Golden Delicious apples from three geographical regions in the Netherlands were stored at 4 degrees C in a controlled atmosphere (CA) of 9% CO2, 12% 02 and under normal atomspheric conditions (Air = A). They were judged with the aid of a palatability test after which it was established that the internal quality of a population of fruits remained satisfactory until they reached a range of L-malate of 0.39-0.45 g per 100 g initial fresh weight.", "contents": "L-malate in golden delicious apples as a possible parameter of acceptability. Several batches of Golden Delicious apples from three geographical regions in the Netherlands were stored at 4 degrees C in a controlled atmosphere (CA) of 9% CO2, 12% 02 and under normal atomspheric conditions (Air = A). They were judged with the aid of a palatability test after which it was established that the internal quality of a population of fruits remained satisfactory until they reached a range of L-malate of 0.39-0.45 g per 100 g initial fresh weight."} {"id": "PMID:1266416", "title": "[Lead content of Hungarian wines (author's transl)].", "content": "The authors have investigated the lead content of 560 hungarian wines produced between 1969 and 1973 by atomic absorption spectrophotometry (Type of instrument: UNICAM SP 1900). The preparation of samples was made by wet digestion with HNO3-H202. For 94.12% of the investigated wines less than 0.4 ppm lead content was established. The 2.67% of wines contain 0.4-0.6 ppm lead. In case of 18 samples (3.21%) more than 0.6 ppm lead content was found.", "contents": "[Lead content of Hungarian wines (author's transl)]. The authors have investigated the lead content of 560 hungarian wines produced between 1969 and 1973 by atomic absorption spectrophotometry (Type of instrument: UNICAM SP 1900). The preparation of samples was made by wet digestion with HNO3-H202. For 94.12% of the investigated wines less than 0.4 ppm lead content was established. The 2.67% of wines contain 0.4-0.6 ppm lead. In case of 18 samples (3.21%) more than 0.6 ppm lead content was found."} {"id": "PMID:1266417", "title": "[The importance of temperature on storage of ground natural spices (author's transl)].", "content": "Several factors influencing the ingredients of volative oils of some ground natural spices have been investigated during storage. The effects on the aroma have been characterized sensorically; relations between the analytical and sensorical results are explained using anise as an example. Of the influencing factors studied such as packaging material, storage temperature and storage duration, the storage temperature must be regarded as the most important.", "contents": "[The importance of temperature on storage of ground natural spices (author's transl)]. Several factors influencing the ingredients of volative oils of some ground natural spices have been investigated during storage. The effects on the aroma have been characterized sensorically; relations between the analytical and sensorical results are explained using anise as an example. Of the influencing factors studied such as packaging material, storage temperature and storage duration, the storage temperature must be regarded as the most important."} {"id": "PMID:1266418", "title": "[Effect of D-penicillamine and 2-mercaptoethanol on human IgM in normal serum].", "content": "Serum from healthy blood donors (O Rh+) was fractionated on a Sephadex-G-200 column before and after incubation with equal volumes of either 0.2 m 2-Mercaptoethanol or D-Penicillamine. Immunoelectrophoretic analyses revealed that addition of these two sulphhydryl-containing compounds resulted in disappearance of the typical IgM-precipitate within the first peak. A new precipitate specific for M-chains appeared within the second peak. The data indicate that the smaller subunits with M-chain specificity result from splitting of disulphide bonds of the IgM molecules by the D-Penicillamine and the 2-Mercaptoethanol.", "contents": "[Effect of D-penicillamine and 2-mercaptoethanol on human IgM in normal serum]. Serum from healthy blood donors (O Rh+) was fractionated on a Sephadex-G-200 column before and after incubation with equal volumes of either 0.2 m 2-Mercaptoethanol or D-Penicillamine. Immunoelectrophoretic analyses revealed that addition of these two sulphhydryl-containing compounds resulted in disappearance of the typical IgM-precipitate within the first peak. A new precipitate specific for M-chains appeared within the second peak. The data indicate that the smaller subunits with M-chain specificity result from splitting of disulphide bonds of the IgM molecules by the D-Penicillamine and the 2-Mercaptoethanol."} {"id": "PMID:1266419", "title": "[Acute mediastinitis in rheumatoid arthritis)].", "content": "During an exacerbation of rheumatoid arthritis in a 54 year old woman, an acute lifethreatening complication developed with pleuro-mediastino-pericarditis presenting as a superior vena cava obstruction-like syndrome. This was later associated with thrombosis of the left external jugular vein and a peripheral Horner's syndrome. She did also develop arterial hypertension with retinopathy and severe cardiac failure. Treatment with antirheumatic drugs and penicillin resulted in gradual improvement over the course of several months. The affected visceral organs were not permanently damaged. Knowledge of the clinical features of this condition is important, since a cure even with conservative treatment is possible.", "contents": "[Acute mediastinitis in rheumatoid arthritis)]. During an exacerbation of rheumatoid arthritis in a 54 year old woman, an acute lifethreatening complication developed with pleuro-mediastino-pericarditis presenting as a superior vena cava obstruction-like syndrome. This was later associated with thrombosis of the left external jugular vein and a peripheral Horner's syndrome. She did also develop arterial hypertension with retinopathy and severe cardiac failure. Treatment with antirheumatic drugs and penicillin resulted in gradual improvement over the course of several months. The affected visceral organs were not permanently damaged. Knowledge of the clinical features of this condition is important, since a cure even with conservative treatment is possible."} {"id": "PMID:1266420", "title": "[Pulmonary manifestations of lupus erythematodes visceralis].", "content": "Eight patients with SLE were found on clinical and roentgenological grounds or by respiratory function tests to have evidence of lung involvement. Great discrepancies were noted between clinical findings and the results of the respiratory function tests on the one hand and lacking or discrete radiological changes on the other hand. Four patients with pulmonary fibrosis without auscultatory signs showed decreased compliance values and decreased diffusion and vital capacities were noticed in two. In only 2 out of 4 patients with abnormal clinical signs could fibrotic changes be detected roentgenologically. Corresponding to the general diagnostic experience the measurement of compliance, diffusion capacity and vital capacity are the most appropriate methodes for assessing these visceral manifestations of SLE.", "contents": "[Pulmonary manifestations of lupus erythematodes visceralis]. Eight patients with SLE were found on clinical and roentgenological grounds or by respiratory function tests to have evidence of lung involvement. Great discrepancies were noted between clinical findings and the results of the respiratory function tests on the one hand and lacking or discrete radiological changes on the other hand. Four patients with pulmonary fibrosis without auscultatory signs showed decreased compliance values and decreased diffusion and vital capacities were noticed in two. In only 2 out of 4 patients with abnormal clinical signs could fibrotic changes be detected roentgenologically. Corresponding to the general diagnostic experience the measurement of compliance, diffusion capacity and vital capacity are the most appropriate methodes for assessing these visceral manifestations of SLE."} {"id": "PMID:1266421", "title": "The effect of complete Freund--adjuvant on chronic proliferating inflammation in an experimental granuloma model.", "content": "Histometric, biochemical, radiochemical and autoradiographic studies were undertaken to investigate the influence of complete Freund-adjuvant (CFA) on a defined chronic proliferating inflammation of a granuloma model in two different experimental situations. Where as the percentage fraction of the fibroblasts, 3H-thymidine marking index of the fibroblasts and the impulse rate of the fibroblasts and endothelial cells do not differ from the values found for the control animals, both the protein and DNA content of the implanted sponges, as well as the DNA content of the individual fibroblasts in the implants increased, independent of the stage of the chronic proliferating inflammation at which the CFA was administered. Surprisingly the quantity of the fibroblast specific synthetic product, collagen, did not increase in proportion to the absolute number of fibroblasts, but remained either constant or even significantly decreased. A possible inhibition of collagen synthesis after CFA administration during chronic proliferating inflammation is discussed.", "contents": "The effect of complete Freund--adjuvant on chronic proliferating inflammation in an experimental granuloma model. Histometric, biochemical, radiochemical and autoradiographic studies were undertaken to investigate the influence of complete Freund-adjuvant (CFA) on a defined chronic proliferating inflammation of a granuloma model in two different experimental situations. Where as the percentage fraction of the fibroblasts, 3H-thymidine marking index of the fibroblasts and the impulse rate of the fibroblasts and endothelial cells do not differ from the values found for the control animals, both the protein and DNA content of the implanted sponges, as well as the DNA content of the individual fibroblasts in the implants increased, independent of the stage of the chronic proliferating inflammation at which the CFA was administered. Surprisingly the quantity of the fibroblast specific synthetic product, collagen, did not increase in proportion to the absolute number of fibroblasts, but remained either constant or even significantly decreased. A possible inhibition of collagen synthesis after CFA administration during chronic proliferating inflammation is discussed."} {"id": "PMID:1266422", "title": "[Ceruloplasmin and immunoglobulins under controlled D-penicillamine therapy in rheumatoid arthritis].", "content": "In a controlled therapeutic trial 17 patients with active rheumatoid arthritis (stage II and III) were divided in two randomized groups. One group of 9 patients was treated with 900 mg of D(-)penicillamine (Trolovol) plus 1500 mg of salicylate per day, the other group of 8 patients with 10 mg of prednisolone plus 1500 mg of salicylate daily. Before and after 1, 2, 3, 4 and 6 months of treatment IgA, IgG, IgM and caeruloplasmin were estimated with immunodiffusion technique. In both groups the IgA and IgG levels remained unchanged; unter D-penicillamine, on the contrary, a statistically significant and continuous fall of IgM and caeruloplasmin was observed; prednisolone treatment induced only a temporary fall of caeruloplasmin. In the DPA treated patients, a significant correlation of IgM with caeruloplasmin and of caeruloplasmin with ESR was found. In both groups there was no correlation between joint count and caeruloplasmin, joint count and IgM, caeruloplasmin and copper, copper and ESR; in the prednisolone group no correlation between caeruloplasmin, ESR and IgM was observed. The correlations suggest that the remarkable fall of IgM and caeruloplasmin under D(-)penicillamine treatment is caused at least partially by direct interference of DPA with these plasma proteins.", "contents": "[Ceruloplasmin and immunoglobulins under controlled D-penicillamine therapy in rheumatoid arthritis]. In a controlled therapeutic trial 17 patients with active rheumatoid arthritis (stage II and III) were divided in two randomized groups. One group of 9 patients was treated with 900 mg of D(-)penicillamine (Trolovol) plus 1500 mg of salicylate per day, the other group of 8 patients with 10 mg of prednisolone plus 1500 mg of salicylate daily. Before and after 1, 2, 3, 4 and 6 months of treatment IgA, IgG, IgM and caeruloplasmin were estimated with immunodiffusion technique. In both groups the IgA and IgG levels remained unchanged; unter D-penicillamine, on the contrary, a statistically significant and continuous fall of IgM and caeruloplasmin was observed; prednisolone treatment induced only a temporary fall of caeruloplasmin. In the DPA treated patients, a significant correlation of IgM with caeruloplasmin and of caeruloplasmin with ESR was found. In both groups there was no correlation between joint count and caeruloplasmin, joint count and IgM, caeruloplasmin and copper, copper and ESR; in the prednisolone group no correlation between caeruloplasmin, ESR and IgM was observed. The correlations suggest that the remarkable fall of IgM and caeruloplasmin under D(-)penicillamine treatment is caused at least partially by direct interference of DPA with these plasma proteins."} {"id": "PMID:1266423", "title": "[Deep vein thrombosis in the differential diagnosis of knee-joint capsule changes in rheumatoid arthritis].", "content": "The authors describe 5 patients with rheumatoid arthritis; in 3 patients rupture of the synovial membrane and in 2 patients a calf cyst caused symptoms resembling a deep vein thrombosis. Contrast arthrography is of great help in differential diagnosis in conjunction with thorough anamnesis and clinical examination. The joint effusion plays a dominating role in the disease process, and treatment of the effusion is of the greatest importance for both prophylaxis and therapy of membrane rupture and calf cysts.", "contents": "[Deep vein thrombosis in the differential diagnosis of knee-joint capsule changes in rheumatoid arthritis]. The authors describe 5 patients with rheumatoid arthritis; in 3 patients rupture of the synovial membrane and in 2 patients a calf cyst caused symptoms resembling a deep vein thrombosis. Contrast arthrography is of great help in differential diagnosis in conjunction with thorough anamnesis and clinical examination. The joint effusion plays a dominating role in the disease process, and treatment of the effusion is of the greatest importance for both prophylaxis and therapy of membrane rupture and calf cysts."} {"id": "PMID:1266424", "title": "[Influence of knee synovectomy on the disease course in PCP patients].", "content": "72 patients with rheumatoid arthritis undergoing surgical synovectomy of knee joints (102 times) were followed up for five years at yearly intervals for their clinical condition and laboratory parameters (sed. rate, leukocytes, serum iron, rheumatoid factor and others). Findings were documented by use of a questionary. At the end of the study the result of synovectomy was compared with the preoperative disease state by use of the Steinbrocker-Criteria and laboratory findings; in addition influence of synovectomy on the postoperative course was investigated. The following conclusions were drawn. 1) Preoperatively seronegative patients exhibited better local long term recovery than seropositive patients. 2) In most patients synovectomized in stage I the disease did not progress during the study period. 3) Some of the patients showed retardation of immunoserologic disease activity for 2-3 years after synovectomy.", "contents": "[Influence of knee synovectomy on the disease course in PCP patients]. 72 patients with rheumatoid arthritis undergoing surgical synovectomy of knee joints (102 times) were followed up for five years at yearly intervals for their clinical condition and laboratory parameters (sed. rate, leukocytes, serum iron, rheumatoid factor and others). Findings were documented by use of a questionary. At the end of the study the result of synovectomy was compared with the preoperative disease state by use of the Steinbrocker-Criteria and laboratory findings; in addition influence of synovectomy on the postoperative course was investigated. The following conclusions were drawn. 1) Preoperatively seronegative patients exhibited better local long term recovery than seropositive patients. 2) In most patients synovectomized in stage I the disease did not progress during the study period. 3) Some of the patients showed retardation of immunoserologic disease activity for 2-3 years after synovectomy."} {"id": "PMID:1266428", "title": "Social behavior of the conilurine rodents (Muridae) of Australia.", "content": "This paper describes in detail the elements of social behaviour and social organizations of four closely related rodents (Notomys alexis, Pseudomys albocinereus, P. shortridgei and P. desertor) from diverse habitats, and the social organizations of seven other conilurine rodents are described briefly. Most of the data were determined from quantitative observations of animals caged in twos or in larger groups for at least ten days. Breeding pairs were observed daily throughout pregnancy and parenthood. A dispersed organization and three types of communal organization are described, and evolutionary trends in dispersion and territoriality, cohesion, communication and co-operation are discussed.", "contents": "Social behavior of the conilurine rodents (Muridae) of Australia. This paper describes in detail the elements of social behaviour and social organizations of four closely related rodents (Notomys alexis, Pseudomys albocinereus, P. shortridgei and P. desertor) from diverse habitats, and the social organizations of seven other conilurine rodents are described briefly. Most of the data were determined from quantitative observations of animals caged in twos or in larger groups for at least ten days. Breeding pairs were observed daily throughout pregnancy and parenthood. A dispersed organization and three types of communal organization are described, and evolutionary trends in dispersion and territoriality, cohesion, communication and co-operation are discussed."} {"id": "PMID:1266449", "title": "[Antibacterial and antiviral activity of beta,beta-dichlorvinylpyrrolidone].", "content": "Antiviral and antibacterial activity of chlorine-containing N-vinylpyrrholidon analogue - beta,beta-dichlorvinylpyrrholidon (first synthesized in 1970) was studied on a model of influenza A2 virus. Peculiarities of the influence of beta,beta-dichlorvinylpyrrholidon on the reproduction of microbial and viral agents under conditions of their isolated and combined cultivation were revealed.", "contents": "[Antibacterial and antiviral activity of beta,beta-dichlorvinylpyrrolidone]. Antiviral and antibacterial activity of chlorine-containing N-vinylpyrrholidon analogue - beta,beta-dichlorvinylpyrrholidon (first synthesized in 1970) was studied on a model of influenza A2 virus. Peculiarities of the influence of beta,beta-dichlorvinylpyrrholidon on the reproduction of microbial and viral agents under conditions of their isolated and combined cultivation were revealed."} {"id": "PMID:1266450", "title": "[Determination of the sensitivity of head lice to insecticides].", "content": "The author recommends a method of determination of sensitivity of head lice which, in difference from the accepted one, is based on the establishment of the time interval between the death of 50-100% of the insects as a result of the contact with the insecticide in definite doses of the active substance. The method permits to assess the rapidity and the extent of the toxic action of various substances on lice; it is simple and convenient for use in practice.", "contents": "[Determination of the sensitivity of head lice to insecticides]. The author recommends a method of determination of sensitivity of head lice which, in difference from the accepted one, is based on the establishment of the time interval between the death of 50-100% of the insects as a result of the contact with the insecticide in definite doses of the active substance. The method permits to assess the rapidity and the extent of the toxic action of various substances on lice; it is simple and convenient for use in practice."} {"id": "PMID:1266451", "title": "[Evaluation of the epidemiological effectiveness of hospitalization of patients with dysentery].", "content": "The authors present materials on the study of epidemiological efficacy of hospitalization of dysentery patients by statistical analysis (calculation of tendencies, rates of increase, etc.) of the indices of focal morbidity per 1000 contacts in the total number of foci characterized by various periods of isolation of the first patient. The work was carried out on materials of two towns considerably differing by the extent of organization of public services and amenities. The results obtained pointed to the relative epidemiological efficacy of hospitalization of dysentery patients particularly marked at the territory with less favourable living conditions.", "contents": "[Evaluation of the epidemiological effectiveness of hospitalization of patients with dysentery]. The authors present materials on the study of epidemiological efficacy of hospitalization of dysentery patients by statistical analysis (calculation of tendencies, rates of increase, etc.) of the indices of focal morbidity per 1000 contacts in the total number of foci characterized by various periods of isolation of the first patient. The work was carried out on materials of two towns considerably differing by the extent of organization of public services and amenities. The results obtained pointed to the relative epidemiological efficacy of hospitalization of dysentery patients particularly marked at the territory with less favourable living conditions."} {"id": "PMID:1266452", "title": "[Use of erythrocyte diagnostic agents for the determination of integrative association constants].", "content": "The authors described a method of determination of integrative association constant differing from intrinsic association constant by the value of the valency of macromolecular antigen. The method is based on the using of erythrocytes on whose surface one of the components is fixed, whereas the other is in free state. Application of equations was demonstratedon a number of examples with determination of integrative association constant. The data obtained permitted to assess qualitative peculiarities of the antigenic and antibody erythrocytic diagnostic agents.", "contents": "[Use of erythrocyte diagnostic agents for the determination of integrative association constants]. The authors described a method of determination of integrative association constant differing from intrinsic association constant by the value of the valency of macromolecular antigen. The method is based on the using of erythrocytes on whose surface one of the components is fixed, whereas the other is in free state. Application of equations was demonstratedon a number of examples with determination of integrative association constant. The data obtained permitted to assess qualitative peculiarities of the antigenic and antibody erythrocytic diagnostic agents."} {"id": "PMID:1266463", "title": "[General regularities of the macrophage reaction in the administration of various antigens and the phagocytosis of microorganisms].", "content": "A study of ingestion and elimination of cells of peritoneal exudate (CPE) of mouse labeled antigens of various physico-chemical nature with a simultaneous analysis of their influence on the function of the enzymatic systems of macrophages showed that both the corpuscular (sheep erythrocytes, typhoid vaccine) and the soluble (albumin, endotoxin of S. typhi, tetanus and staphylococcus toxoid) antigens caused a unitypical reaction of the cells of monocytic phagocytic system. Thirty minutes after the administration the principal mass of labeled antigens (albumin, typhoid vaccine, sheep erythrocytes) was phagocytized by macrophages and was revealed chiefly in their phagolysosomal fraction. The greater part of radioactive material was eliminated in the course of the first 24 hours; however, some of it could be found in the macrophages for a long time. During the process of phagocytosis the activity of lysosomal (catepsin, acid phosphatase, desoxyribonuclease, beta-glucoronidase) enzymes in the macrophages decreased and the activity of redox (succinic dehydrogenase, NAD-N2-diaphorase) enzymes became intensified. A fall of catepsin activity in the CPE of mice 30 minutes after the intraperitoneal administration of the antigens was accompanied by its activation in the cells of the spleen.", "contents": "[General regularities of the macrophage reaction in the administration of various antigens and the phagocytosis of microorganisms]. A study of ingestion and elimination of cells of peritoneal exudate (CPE) of mouse labeled antigens of various physico-chemical nature with a simultaneous analysis of their influence on the function of the enzymatic systems of macrophages showed that both the corpuscular (sheep erythrocytes, typhoid vaccine) and the soluble (albumin, endotoxin of S. typhi, tetanus and staphylococcus toxoid) antigens caused a unitypical reaction of the cells of monocytic phagocytic system. Thirty minutes after the administration the principal mass of labeled antigens (albumin, typhoid vaccine, sheep erythrocytes) was phagocytized by macrophages and was revealed chiefly in their phagolysosomal fraction. The greater part of radioactive material was eliminated in the course of the first 24 hours; however, some of it could be found in the macrophages for a long time. During the process of phagocytosis the activity of lysosomal (catepsin, acid phosphatase, desoxyribonuclease, beta-glucoronidase) enzymes in the macrophages decreased and the activity of redox (succinic dehydrogenase, NAD-N2-diaphorase) enzymes became intensified. A fall of catepsin activity in the CPE of mice 30 minutes after the intraperitoneal administration of the antigens was accompanied by its activation in the cells of the spleen."} {"id": "PMID:1266465", "title": "[Use of the passive hemaglutination reactions for the determination of anti-smallpox antibodies in primary vaccination and revaccination against smallpox].", "content": "The authors present the results of studying the PHAT sensitivity in comparison with the neutralization test and the hemagglutination inhibition test in examination of 254 sera of revaccinated and 95 sera of primarily vaccinated children. It appeared that PHAT was characterized by a sufficiently high sensitivity, and reproducibility, in case the same batch of erythrocytic diagnostic agent was used; at the same time the test was simple, accessible, economic, and gave rapid results. This test can be used for assessment of the immunological efficacy of smallpox revaccination.", "contents": "[Use of the passive hemaglutination reactions for the determination of anti-smallpox antibodies in primary vaccination and revaccination against smallpox]. The authors present the results of studying the PHAT sensitivity in comparison with the neutralization test and the hemagglutination inhibition test in examination of 254 sera of revaccinated and 95 sera of primarily vaccinated children. It appeared that PHAT was characterized by a sufficiently high sensitivity, and reproducibility, in case the same batch of erythrocytic diagnostic agent was used; at the same time the test was simple, accessible, economic, and gave rapid results. This test can be used for assessment of the immunological efficacy of smallpox revaccination."} {"id": "PMID:1266466", "title": "[Quantitative determination of specific immunoglobulins in the serum of bacterial carriers of abdominal typhus].", "content": "As a result of determination of immunoglobulins of class A and M by the method of simple radial immunodiffusion with the use of monospecific antiglobulin sera it appeared that in the sera of carriers immunogolubins M were contained in much lesser quantity than in typhoid patients. The content of immunoglobulins A was somewhat greater in the blood sera of carriers.", "contents": "[Quantitative determination of specific immunoglobulins in the serum of bacterial carriers of abdominal typhus]. As a result of determination of immunoglobulins of class A and M by the method of simple radial immunodiffusion with the use of monospecific antiglobulin sera it appeared that in the sera of carriers immunogolubins M were contained in much lesser quantity than in typhoid patients. The content of immunoglobulins A was somewhat greater in the blood sera of carriers."} {"id": "PMID:1266468", "title": "[IgM and IgG rosette formation in the primary and secondary immune response in the system of syngeneic transfer of spleen cells].", "content": "In the system of syngenous transfer of cells a study was made of the dynamics of IgM- and IgG- of the rosette-froming cells of the spleen in the primary and secondary immune response in mice of the CBA inbred strain immunized with sheep erythrocytes. It was shown that in prolongation of the interval between donor immunization and the transfer of cells to the recipient with his simultaneous immunization for up to 40 days there occurred an increase of the IgG-memory; as to IgM memory-it is expressed with shorter intervals. It is supposed that rosette-forming cells were not bearers of immunological memory.", "contents": "[IgM and IgG rosette formation in the primary and secondary immune response in the system of syngeneic transfer of spleen cells]. In the system of syngenous transfer of cells a study was made of the dynamics of IgM- and IgG- of the rosette-froming cells of the spleen in the primary and secondary immune response in mice of the CBA inbred strain immunized with sheep erythrocytes. It was shown that in prolongation of the interval between donor immunization and the transfer of cells to the recipient with his simultaneous immunization for up to 40 days there occurred an increase of the IgG-memory; as to IgM memory-it is expressed with shorter intervals. It is supposed that rosette-forming cells were not bearers of immunological memory."} {"id": "PMID:1266467", "title": "[Influence of prednisolone on cells erythroid series in the bone marrow of rabbits immunized with diphtheria toxoid].", "content": "The bone marrow reaction to prednisolone showed significant changes after the administration of the antigen: there proved to be a significant reduction of the erythrocyte count, hemoglobin content and of hematocrite. The mean erythrocyte volume increased. Along with this there was a reduction of the number of basophilic and polychromatophilic erythroblasts and an increase in number of proerythroblasts. The degree of depression of the red series of the bone marrow (induced by prednisolone) was much less in case of combined administration of prednisolone and diphtheria toxoid.", "contents": "[Influence of prednisolone on cells erythroid series in the bone marrow of rabbits immunized with diphtheria toxoid]. The bone marrow reaction to prednisolone showed significant changes after the administration of the antigen: there proved to be a significant reduction of the erythrocyte count, hemoglobin content and of hematocrite. The mean erythrocyte volume increased. Along with this there was a reduction of the number of basophilic and polychromatophilic erythroblasts and an increase in number of proerythroblasts. The degree of depression of the red series of the bone marrow (induced by prednisolone) was much less in case of combined administration of prednisolone and diphtheria toxoid."} {"id": "PMID:1266469", "title": "[Use of a computer and mathematical methods in epidemiological work. Report 3. Experience with the operational tracing of infectious morbidity using an automic self-service information unit].", "content": "The authors describe their experience in the elaboration and introduction into practice of epidemiological service of the system of operative tracing of infectious morbidity at the level of the central sanitary-epidemiological station under conditions of automatic control system. Data on improvement of information supply and logic analysis of the information with the aid of Minsk-22 computer are presented. Forms of documents are considered. Experience in the use of this system for two years pointed to its expediency.", "contents": "[Use of a computer and mathematical methods in epidemiological work. Report 3. Experience with the operational tracing of infectious morbidity using an automic self-service information unit]. The authors describe their experience in the elaboration and introduction into practice of epidemiological service of the system of operative tracing of infectious morbidity at the level of the central sanitary-epidemiological station under conditions of automatic control system. Data on improvement of information supply and logic analysis of the information with the aid of Minsk-22 computer are presented. Forms of documents are considered. Experience in the use of this system for two years pointed to its expediency."} {"id": "PMID:1266470", "title": "[Tsutsugamushi fever in the Kuril Islands].", "content": "The authors present the results of a 6-year study of tsutsugamushi fever at the Kuril islands. The area of the disease proved to include Southern Kuril islands - Shikotan and Kunashir. The principal natural carriers of tsutsugamushi among the mouse-like rodents and trombiculidae larvae were revealed; highly virulent strains were found to prevail among the tsutsugamushi rickettsia strains. Tsutsugamushi fever in the population is characterized by a benign course, pyrexia, primary affects and lymphadenitis.", "contents": "[Tsutsugamushi fever in the Kuril Islands]. The authors present the results of a 6-year study of tsutsugamushi fever at the Kuril islands. The area of the disease proved to include Southern Kuril islands - Shikotan and Kunashir. The principal natural carriers of tsutsugamushi among the mouse-like rodents and trombiculidae larvae were revealed; highly virulent strains were found to prevail among the tsutsugamushi rickettsia strains. Tsutsugamushi fever in the population is characterized by a benign course, pyrexia, primary affects and lymphadenitis."} {"id": "PMID:1266471", "title": "[Preservation of the causative agent of tularemia in the external environment in eastern Taimyr].", "content": "Strains of the causative agent of tularemia were for the first time isolated by the authors from the objects of the external environment in the tundra zone of Eastern Taimir; this indicates a possibility of preservation of the microbe under conditions of the extreme north.", "contents": "[Preservation of the causative agent of tularemia in the external environment in eastern Taimyr]. Strains of the causative agent of tularemia were for the first time isolated by the authors from the objects of the external environment in the tundra zone of Eastern Taimir; this indicates a possibility of preservation of the microbe under conditions of the extreme north."} {"id": "PMID:1266472", "title": "[Determination of natural foci of tularemia in the Tuva ASSR].", "content": "Eleven strains of tularemia causative agents were isolated in 1974 in bacteriological study of ixodes ticks Dermacentor nuttalli (13088 in all) by biotests on albino mice. Tularemia was confirmed retrospectively in two humans who contracted the disease from ondatra cadavers. Skin allergic test with tularin was used to examine 1733 residents of seven populated localities; a positive result was obtained in 2 persons. Finally, in examination of 240 sera of cattle agglutination reaction proved to be positive in 6 cases in titres of from 1:20 to 1:80. Thus, natural nidality of tularemia in Tuva was established for the first time.", "contents": "[Determination of natural foci of tularemia in the Tuva ASSR]. Eleven strains of tularemia causative agents were isolated in 1974 in bacteriological study of ixodes ticks Dermacentor nuttalli (13088 in all) by biotests on albino mice. Tularemia was confirmed retrospectively in two humans who contracted the disease from ondatra cadavers. Skin allergic test with tularin was used to examine 1733 residents of seven populated localities; a positive result was obtained in 2 persons. Finally, in examination of 240 sera of cattle agglutination reaction proved to be positive in 6 cases in titres of from 1:20 to 1:80. Thus, natural nidality of tularemia in Tuva was established for the first time."} {"id": "PMID:1266473", "title": "[Use of rooms with laminar air flow].", "content": "The paper deals with the problem of dependency of the reduction of microbial contamination and of dust pollution of the air mediu min the CAMERA-BOXES with a liminary flux on the aeration degree. It was shown that the degree of aeration in the camera-box constituted from 330 to 1060, with the rate of the air flux at the filter exit of from 0.2 to 0.6 m/sec. Vertical laminar flux provided release of the air from the microbes and dust. The use of the camera-box with a laminar flux for work requiring sterile conditions is recommended.", "contents": "[Use of rooms with laminar air flow]. The paper deals with the problem of dependency of the reduction of microbial contamination and of dust pollution of the air mediu min the CAMERA-BOXES with a liminary flux on the aeration degree. It was shown that the degree of aeration in the camera-box constituted from 330 to 1060, with the rate of the air flux at the filter exit of from 0.2 to 0.6 m/sec. Vertical laminar flux provided release of the air from the microbes and dust. The use of the camera-box with a laminar flux for work requiring sterile conditions is recommended."} {"id": "PMID:1266474", "title": "[Neurological sequelae of the generalized forms of meningococcal infection in adults (a catamnestic study of patients who suffered the disease during 1971--1974)].", "content": "The authors conducted a follow-up examination of 118 patients who had meningocaccial meningoencephalitis and meningitis in 1971--1974. Besides a neurological examination the authors performed psychological and EEG studies. It was established that the main expressions of the meningococcial infection during the first 2--3 months following the acute period (and in separate cases up to 1 year and more) were: asthenical syndromes of a different degree, diffuse focal symptoms, neuritis of the cranial nerves, distrubed mental activity and changes in the EEG. For these reasons the estimation of the period of restored working capacity after generalized forms of meningococcical infections should always be strictly individual.", "contents": "[Neurological sequelae of the generalized forms of meningococcal infection in adults (a catamnestic study of patients who suffered the disease during 1971--1974)]. The authors conducted a follow-up examination of 118 patients who had meningocaccial meningoencephalitis and meningitis in 1971--1974. Besides a neurological examination the authors performed psychological and EEG studies. It was established that the main expressions of the meningococcial infection during the first 2--3 months following the acute period (and in separate cases up to 1 year and more) were: asthenical syndromes of a different degree, diffuse focal symptoms, neuritis of the cranial nerves, distrubed mental activity and changes in the EEG. For these reasons the estimation of the period of restored working capacity after generalized forms of meningococcical infections should always be strictly individual."} {"id": "PMID:1266475", "title": "[Treatment of amyotrophic lateral sclerosis with ribonucleotides].", "content": "In the treatment of 31 patients with lateral amyotrophical sclerosis the authors used the preparation ENKAD containing a complex of mono- and oligoribonucleotides. In 6 cases there was aggravation of the condition while in 18 of the observed cases--improvement. In 7 patients the condition was not altered. The treatment was convened under biochemical control (the assessment of the uric acid in the blood serum and urine and the excretion of oxypurine in the urine). It was possible to depict definite clinicobiochemical correlations. The conclusion is made that ENKAD can be used in the early stages of the disease and mainly in focal segmentary-nuclear lesions. The preparation is contraindicated in generalization of the process and in impetuous development of the disorder.", "contents": "[Treatment of amyotrophic lateral sclerosis with ribonucleotides]. In the treatment of 31 patients with lateral amyotrophical sclerosis the authors used the preparation ENKAD containing a complex of mono- and oligoribonucleotides. In 6 cases there was aggravation of the condition while in 18 of the observed cases--improvement. In 7 patients the condition was not altered. The treatment was convened under biochemical control (the assessment of the uric acid in the blood serum and urine and the excretion of oxypurine in the urine). It was possible to depict definite clinicobiochemical correlations. The conclusion is made that ENKAD can be used in the early stages of the disease and mainly in focal segmentary-nuclear lesions. The preparation is contraindicated in generalization of the process and in impetuous development of the disorder."} {"id": "PMID:1266476", "title": "[Preconvulsive state and hyperfunction of the striatum (clinico-experimental findings)].", "content": "The paper is concerned with a clinico-experimental study of the influence of intesified activity in the neostriatum on the EEG indices which may appear during the introduction of increased doses of corazol. In 10 cases with different forms of parkinsonism there was a much easier appearance of clinical and EEG manifestations of convulsive activity, than in normals. In experiments on rats preconvulsive effects were exerted by such neuroleptics as haloperidol unlike apomorphine, possessing opposite properties.", "contents": "[Preconvulsive state and hyperfunction of the striatum (clinico-experimental findings)]. The paper is concerned with a clinico-experimental study of the influence of intesified activity in the neostriatum on the EEG indices which may appear during the introduction of increased doses of corazol. In 10 cases with different forms of parkinsonism there was a much easier appearance of clinical and EEG manifestations of convulsive activity, than in normals. In experiments on rats preconvulsive effects were exerted by such neuroleptics as haloperidol unlike apomorphine, possessing opposite properties."} {"id": "PMID:1266477", "title": "[Primary progressive forms of tick-borne encephalitis].", "content": "The report contains data concerning examinations of 14 patients with a progressive development of tick-borne encephalitis In all the observed cases an acute period in the development of the disease was not diagnosed. The examined contingent constituted 18% of the number of established chronic forms of tick-borne encephalitis. The states were mostly latent forms of infections which were much more frequent than clinically forms of tick-borne encephalitis.", "contents": "[Primary progressive forms of tick-borne encephalitis]. The report contains data concerning examinations of 14 patients with a progressive development of tick-borne encephalitis In all the observed cases an acute period in the development of the disease was not diagnosed. The examined contingent constituted 18% of the number of established chronic forms of tick-borne encephalitis. The states were mostly latent forms of infections which were much more frequent than clinically forms of tick-borne encephalitis."} {"id": "PMID:1266478", "title": "[Clinico-immunologic features of tick-borne encephalitis in the Tomsk region].", "content": "In 243 patients with tick-borne encephalitis 60.9% had an oblivated form, 21.3%--the meningeal, 2.5% encephalitic, 2.9%--polyencephalomyelitic and 12.4%--doublewave development of the disease. In all cases the clinical picture, blood and CSF content of asparite-aminotransferase and alanine aminotransferase was studied. The study included the level of urine diastase, blood histamine, autoantibodies and indices of destructed blood neutrophils. It was established that tick-borne encephalitis remains one of the most serious diseases of the nervous system which is accompanied by lesions of the internal organs. Changes in the studied indices are in direct correlation with the form and severity of the disease. They do not come to norm even at the moment of hospital discharge which indicates the continuation of the process.", "contents": "[Clinico-immunologic features of tick-borne encephalitis in the Tomsk region]. In 243 patients with tick-borne encephalitis 60.9% had an oblivated form, 21.3%--the meningeal, 2.5% encephalitic, 2.9%--polyencephalomyelitic and 12.4%--doublewave development of the disease. In all cases the clinical picture, blood and CSF content of asparite-aminotransferase and alanine aminotransferase was studied. The study included the level of urine diastase, blood histamine, autoantibodies and indices of destructed blood neutrophils. It was established that tick-borne encephalitis remains one of the most serious diseases of the nervous system which is accompanied by lesions of the internal organs. Changes in the studied indices are in direct correlation with the form and severity of the disease. They do not come to norm even at the moment of hospital discharge which indicates the continuation of the process."} {"id": "PMID:1266479", "title": "[Clinical variants of epidemic encephalitis in Primor'e].", "content": "The authors examined 104 patients with epidemic encephalitis (48 in the acute stage and 56 in chronic). In the acute stage the following forms were distinguished: vestibular, lethargic, hyperkinetic and psychosensory. The chronic stage included postencephalitic parkinsonism, hyperkinetic and lethargic forms. The acute stage had a mild development without lethal outcomes. The specific traits of epidemic encephalitis in this region were the frequency of vestibular forms in the acute stage and hyperkinetic forms in the chronic one.", "contents": "[Clinical variants of epidemic encephalitis in Primor'e]. The authors examined 104 patients with epidemic encephalitis (48 in the acute stage and 56 in chronic). In the acute stage the following forms were distinguished: vestibular, lethargic, hyperkinetic and psychosensory. The chronic stage included postencephalitic parkinsonism, hyperkinetic and lethargic forms. The acute stage had a mild development without lethal outcomes. The specific traits of epidemic encephalitis in this region were the frequency of vestibular forms in the acute stage and hyperkinetic forms in the chronic one."} {"id": "PMID:1266480", "title": "[Catamnesis of patients sustaining the acute period of epidemic encephalitis in Primor'e].", "content": "The authors studied 20 patients (12 males and 8 females) from 5--40 years of age who had acute forms of epidemic encephalitis. Progressive development was marked only in 2 patients (in one case typical parkinsonism, in the other--a hallucinatory-paranoid schizophrenoform syndrome). In the majority of the cases neurological symptoms of the acute period gradually subsided up till a full disappearance (in 8 out of 20 cases). Among the residual of symptoms of contemporary epidemic encephalitis special attention should be drawn to blepharoclonus and blepharospasm, converging both monocular nistagmus and peculiar \"psychic equivalents\" of parkinsonism in the form of akairia. These symptoms may be used for a retrospective diagnosis of epidemic encephalitis.", "contents": "[Catamnesis of patients sustaining the acute period of epidemic encephalitis in Primor'e]. The authors studied 20 patients (12 males and 8 females) from 5--40 years of age who had acute forms of epidemic encephalitis. Progressive development was marked only in 2 patients (in one case typical parkinsonism, in the other--a hallucinatory-paranoid schizophrenoform syndrome). In the majority of the cases neurological symptoms of the acute period gradually subsided up till a full disappearance (in 8 out of 20 cases). Among the residual of symptoms of contemporary epidemic encephalitis special attention should be drawn to blepharoclonus and blepharospasm, converging both monocular nistagmus and peculiar \"psychic equivalents\" of parkinsonism in the form of akairia. These symptoms may be used for a retrospective diagnosis of epidemic encephalitis."} {"id": "PMID:1266481", "title": "[A clinico-electroneurographic study of brachial plexitis in young children].", "content": "In order to study the clinico-electroneurographical correlations in early brachial plexitis of the newborn the authors studied 118 children from the moment of birth up to 1.5-4 years. The depicted disorders were divided into 4 groups: the upper form of Duchenne-Erb--48 cases; the lower forms of Dejerine-Klumpke--27 cases; total forms--31 cases and bilateral forms--12 cases. The most favourable development could be marked in the Duchenne-Erb forms while the most severe development was seen in total forms. The authors stress that electroneurographical studies permit to evaluate objectively the severity of affection, the degree of motor function restoration, the effectiveness of treatment and the prognosis of the disease.", "contents": "[A clinico-electroneurographic study of brachial plexitis in young children]. In order to study the clinico-electroneurographical correlations in early brachial plexitis of the newborn the authors studied 118 children from the moment of birth up to 1.5-4 years. The depicted disorders were divided into 4 groups: the upper form of Duchenne-Erb--48 cases; the lower forms of Dejerine-Klumpke--27 cases; total forms--31 cases and bilateral forms--12 cases. The most favourable development could be marked in the Duchenne-Erb forms while the most severe development was seen in total forms. The authors stress that electroneurographical studies permit to evaluate objectively the severity of affection, the degree of motor function restoration, the effectiveness of treatment and the prognosis of the disease."} {"id": "PMID:1266482", "title": "[Changes in several hemodynamic indices in cerebral arachnoiditis[].", "content": "The author examined 195 patients from 17 to 60 years with cerebral arachnoiditis. The following haemodynamical factors were analyzed: rheoencephalograms, synchronous rigistration of the REG and EEG, peripheral and retinal pressures. The studies showed tow tendencies of the haemodynamic changes: regional hypertonicity and hypotonicity. The specificity of the haemodynamic factors depends on the phase of the hypertensive syndrome and the duration of the disease.", "contents": "[Changes in several hemodynamic indices in cerebral arachnoiditis[]. The author examined 195 patients from 17 to 60 years with cerebral arachnoiditis. The following haemodynamical factors were analyzed: rheoencephalograms, synchronous rigistration of the REG and EEG, peripheral and retinal pressures. The studies showed tow tendencies of the haemodynamic changes: regional hypertonicity and hypotonicity. The specificity of the haemodynamic factors depends on the phase of the hypertensive syndrome and the duration of the disease."} {"id": "PMID:1266483", "title": "[Cerebrospinal fluid phospholipids and cerebrosides in several demyelinating diseases].", "content": "The author reports of the achieved results in a quantitative study of general lipids, phospholipids and cerebrosides in the CSF of 37 patients with demyelinating diseases, of 11 patients with vascular brain pathology and 7 with Van Bogart's panencephalitis. The control group consisted of 14 patients without focal lesions of the nervous system, with normal CSF indices. In demyelinating diseases there was a significant increase in the content of kephalines and cerebrosides. In Van Bogart's panencephalitis there was a much higher increase of kephalines, general lipids and phospholipids. In vascular brain disorders there was a moderate increase of all lipids. The possible pathochemical mechanisms of the depicted changes in the content of the lipids in the CSF are discussed.", "contents": "[Cerebrospinal fluid phospholipids and cerebrosides in several demyelinating diseases]. The author reports of the achieved results in a quantitative study of general lipids, phospholipids and cerebrosides in the CSF of 37 patients with demyelinating diseases, of 11 patients with vascular brain pathology and 7 with Van Bogart's panencephalitis. The control group consisted of 14 patients without focal lesions of the nervous system, with normal CSF indices. In demyelinating diseases there was a significant increase in the content of kephalines and cerebrosides. In Van Bogart's panencephalitis there was a much higher increase of kephalines, general lipids and phospholipids. In vascular brain disorders there was a moderate increase of all lipids. The possible pathochemical mechanisms of the depicted changes in the content of the lipids in the CSF are discussed."} {"id": "PMID:1266484", "title": "[The bioelectrical activity of the brain in Urov (Kashin-Bek) disease].", "content": "EEG studies of 112 patients in different stages of the uric (Kashin-Beck) disease revealed pathological shifts in the brain biopotentials, which were beyond the aging changes. Analysis of the EEG tracing demonstrated that the index of alpha-activity along with a progressive severity of the disease, especially in the 2nd and 3d stage, was statistically less, while the per cent of pathological forms of potentials increased. In a rhythmic photostimulation there were disorders in the brain reactivity. These data point to a diffuse lesion of the brain. A correlation between clinical, EEG and other studies permit to consider the uric disease as a chronic disorder leading to an early aging of the organism.", "contents": "[The bioelectrical activity of the brain in Urov (Kashin-Bek) disease]. EEG studies of 112 patients in different stages of the uric (Kashin-Beck) disease revealed pathological shifts in the brain biopotentials, which were beyond the aging changes. Analysis of the EEG tracing demonstrated that the index of alpha-activity along with a progressive severity of the disease, especially in the 2nd and 3d stage, was statistically less, while the per cent of pathological forms of potentials increased. In a rhythmic photostimulation there were disorders in the brain reactivity. These data point to a diffuse lesion of the brain. A correlation between clinical, EEG and other studies permit to consider the uric disease as a chronic disorder leading to an early aging of the organism."} {"id": "PMID:1266485", "title": "[Penetration of anti-cerebral antibodies through the blood-brain and placental barriers of animals].", "content": "The report deals with studies of the penetration of gamma-globulin I131 of rabbit antibrain sera into the different brain areas of intact and sensitized rats and into the placenta of embryo tissues. It was demonstrated that lebeled I131 gamma-globulin containing antibodies to homo- and heterologous brain may in a small amount penetrate from the blood into the CNS of animals. The authors demonstrated as well that labelled antibodies penetrated from the blood of pregnant rats through the placenta and accumulated in the brain and internal organs of the embryo. These facts are significant for development of pathogenesis of an antenatal brain pathology.", "contents": "[Penetration of anti-cerebral antibodies through the blood-brain and placental barriers of animals]. The report deals with studies of the penetration of gamma-globulin I131 of rabbit antibrain sera into the different brain areas of intact and sensitized rats and into the placenta of embryo tissues. It was demonstrated that lebeled I131 gamma-globulin containing antibodies to homo- and heterologous brain may in a small amount penetrate from the blood into the CNS of animals. The authors demonstrated as well that labelled antibodies penetrated from the blood of pregnant rats through the placenta and accumulated in the brain and internal organs of the embryo. These facts are significant for development of pathogenesis of an antenatal brain pathology."} {"id": "PMID:1266486", "title": "[Dreams under normal conditions and in pathology].", "content": "Experiments on wakening from \"rapid\" and \"slow\" sleep, as well as clinical and epidemiological studies revealed differences in the reports of dreams. These differences were in correlation with the character of cerebral or somatical pathology and with the representativeness of phasic components of \"rapid\" sleep.", "contents": "[Dreams under normal conditions and in pathology]. Experiments on wakening from \"rapid\" and \"slow\" sleep, as well as clinical and epidemiological studies revealed differences in the reports of dreams. These differences were in correlation with the character of cerebral or somatical pathology and with the representativeness of phasic components of \"rapid\" sleep."} {"id": "PMID:1266487", "title": "[Clinical findings concerning a comparative study of several structural features of depression].", "content": "The author studied 321 patients with depressive states of a different nature (reactive, symptomatical and endogenous). An attempt is made to establish connections between atypical neurotical states and hallucinatory-paranoid symptoms on the one hand and certain depressive emotions on the other. The opinion is expressed that anguish to a greater extent prevents the polymorphism of a depressive affect and the appearance of nonemotional disorders.", "contents": "[Clinical findings concerning a comparative study of several structural features of depression]. The author studied 321 patients with depressive states of a different nature (reactive, symptomatical and endogenous). An attempt is made to establish connections between atypical neurotical states and hallucinatory-paranoid symptoms on the one hand and certain depressive emotions on the other. The opinion is expressed that anguish to a greater extent prevents the polymorphism of a depressive affect and the appearance of nonemotional disorders."} {"id": "PMID:1266488", "title": "[Electrolyte metabolism in alcoholic patients during therapy and prolonged abstinence].", "content": "The author studied the dynamics of development of the Na+ and K+ content in the blood plasma, erythrocytes and urine in 82 patients with chronic alcoholism during the period of active antialcohol treatment. It was established that the content of Na in the blood plasma was decreased while its excretion with urine increased. Signs of mineral-corticoid insufficiency remained even 2--3 years following treatment.", "contents": "[Electrolyte metabolism in alcoholic patients during therapy and prolonged abstinence]. The author studied the dynamics of development of the Na+ and K+ content in the blood plasma, erythrocytes and urine in 82 patients with chronic alcoholism during the period of active antialcohol treatment. It was established that the content of Na in the blood plasma was decreased while its excretion with urine increased. Signs of mineral-corticoid insufficiency remained even 2--3 years following treatment."} {"id": "PMID:1266489", "title": "[Features of hepatic lesions in patients with chronic alcoholic intoxication].", "content": "The authors studied alcoholic hepatosis and hepatic cirrhosis by laboratory, radioisotope and clinical methods. Most of the routine laboratory techniques, excluding hyperurobilinuria were not very informative in alcoholic hepatosis. Much more frequently it was possible to mark disturbances of the bromsulphaleinic and vofaverdine tests. Of special importance in the evaluation of the acuity and depth of the alcohol intoxication was glutamate and sorbitdehydrogenase. The most informative appeared to be radioisotope hepatography in the phase of alcohol hepatosis and scannography in the formation of liver cirrhosis.", "contents": "[Features of hepatic lesions in patients with chronic alcoholic intoxication]. The authors studied alcoholic hepatosis and hepatic cirrhosis by laboratory, radioisotope and clinical methods. Most of the routine laboratory techniques, excluding hyperurobilinuria were not very informative in alcoholic hepatosis. Much more frequently it was possible to mark disturbances of the bromsulphaleinic and vofaverdine tests. Of special importance in the evaluation of the acuity and depth of the alcohol intoxication was glutamate and sorbitdehydrogenase. The most informative appeared to be radioisotope hepatography in the phase of alcohol hepatosis and scannography in the formation of liver cirrhosis."} {"id": "PMID:1266490", "title": "[Mental disorder in strangulation asphyxia].", "content": "In order to study the mental, neurological and EEG changes due to strangulative asphyxia, the authors studied 163 patients who attempted suicide by selfhanging. In the poststrangulative period there was changed consciousness, disorders of memory, emotions, as well as neurological symptoms which eventually had a reversible course. All these data were confirmed by EEG studies. The convened investigation demonstrated a high therapeutical effect of modern resuscitative measures which can be rendered to this contingent of patients.", "contents": "[Mental disorder in strangulation asphyxia]. In order to study the mental, neurological and EEG changes due to strangulative asphyxia, the authors studied 163 patients who attempted suicide by selfhanging. In the poststrangulative period there was changed consciousness, disorders of memory, emotions, as well as neurological symptoms which eventually had a reversible course. All these data were confirmed by EEG studies. The convened investigation demonstrated a high therapeutical effect of modern resuscitative measures which can be rendered to this contingent of patients."} {"id": "PMID:1266491", "title": "[Mental disorders in chronic mercury poisoning].", "content": "On the basis of studies performed in a psychoneurological dispensary the author examined 60 patients who worked in noxious conditions of chronic micromercuralism from 1--10 years. A thorough clinical observation permitted to distinguish the following psychopathological syndromes: asthenical (the most frequent initial expression of the disorder), depression, psychopath-like and epileptiform.", "contents": "[Mental disorders in chronic mercury poisoning]. On the basis of studies performed in a psychoneurological dispensary the author examined 60 patients who worked in noxious conditions of chronic micromercuralism from 1--10 years. A thorough clinical observation permitted to distinguish the following psychopathological syndromes: asthenical (the most frequent initial expression of the disorder), depression, psychopath-like and epileptiform."} {"id": "PMID:1266492", "title": "[Hyperbaric oxygen therapy in the clinical treatment of mental disorders accompanying severe cranio-cerebral trauma].", "content": "The author examined 20 patients with severe brain damage. Under the influence of hyperbaric oxygen therapy there was a more rapid restitution of consciousness and a relatively short development of soporous and comatose conditions. Disoders of the Korsakoff syndrome type in such conditions had an abortive development as well (4--7 days). In cases of developing delirious states the use of hyperbaric oxygen therapy demonstrated a clearing of consciousness and a disappearance of psychotic disturbances, already following the first session.", "contents": "[Hyperbaric oxygen therapy in the clinical treatment of mental disorders accompanying severe cranio-cerebral trauma]. The author examined 20 patients with severe brain damage. Under the influence of hyperbaric oxygen therapy there was a more rapid restitution of consciousness and a relatively short development of soporous and comatose conditions. Disoders of the Korsakoff syndrome type in such conditions had an abortive development as well (4--7 days). In cases of developing delirious states the use of hyperbaric oxygen therapy demonstrated a clearing of consciousness and a disappearance of psychotic disturbances, already following the first session."} {"id": "PMID:1266493", "title": "[The differential diagnosis of severe poisoning using electroencephalographic findings].", "content": "The author conducted a clinical and EEG study of 308 patients with severe acute poisoning (by barbiturates, phosphororganic compounds, ethyl alcohol, noxiron, elenium, narcotics, carbon monoxide, tubazide, ethylenglycole and dichlorethan). It is shown that EEG changes in combination with clinical and toxicological data permit to qualify more precisely the form of poisoning and conduct specific therapy.", "contents": "[The differential diagnosis of severe poisoning using electroencephalographic findings]. The author conducted a clinical and EEG study of 308 patients with severe acute poisoning (by barbiturates, phosphororganic compounds, ethyl alcohol, noxiron, elenium, narcotics, carbon monoxide, tubazide, ethylenglycole and dichlorethan). It is shown that EEG changes in combination with clinical and toxicological data permit to qualify more precisely the form of poisoning and conduct specific therapy."} {"id": "PMID:1266494", "title": "[Assessment of the effectiveness of hemodes in the treatment of the febrile variant of delirium tremens].", "content": "The authors propose a complex scheme in the treatment of a febrile variant of delirium tremens. The main emphasis is made on the use of hemodez possessing an antitoxic property and normalizing metabolism. The use of the mentioned preparation along with neuroleptics and symptomatical therapy as was tried in 30 patients with delirium tremens, permitted to arrest acute disorders, the hyperthermic syndrome and normalize the vital functions of the organism. These measures excluded unfavourable lethal outcomes even in cases complicated by Gayet-Wernicke encephalopathy.", "contents": "[Assessment of the effectiveness of hemodes in the treatment of the febrile variant of delirium tremens]. The authors propose a complex scheme in the treatment of a febrile variant of delirium tremens. The main emphasis is made on the use of hemodez possessing an antitoxic property and normalizing metabolism. The use of the mentioned preparation along with neuroleptics and symptomatical therapy as was tried in 30 patients with delirium tremens, permitted to arrest acute disorders, the hyperthermic syndrome and normalize the vital functions of the organism. These measures excluded unfavourable lethal outcomes even in cases complicated by Gayet-Wernicke encephalopathy."} {"id": "PMID:1266495", "title": "[The character of the effect of triftazin, carbidine and aminazine on defensive conditioned reflexes].", "content": "The author studied in chronical experiment on the rats the influence of triphtazine, karbidine and aminazine on the conditioned reflexes with the irritation of the mesencephalitio part of the reticular formation. The obtained data confirm the inhibitive influence of aminazine on the mesencephalitic part of the reticular formation. Triphtazine and karbidine, alike aminazine, prevent the inhibition of the defensive conditioned reflexes due to the irritation of the mesencephalitis part of the reticular formation testifies to the fact of their inhibitive influence on these structures.", "contents": "[The character of the effect of triftazin, carbidine and aminazine on defensive conditioned reflexes]. The author studied in chronical experiment on the rats the influence of triphtazine, karbidine and aminazine on the conditioned reflexes with the irritation of the mesencephalitio part of the reticular formation. The obtained data confirm the inhibitive influence of aminazine on the mesencephalitic part of the reticular formation. Triphtazine and karbidine, alike aminazine, prevent the inhibition of the defensive conditioned reflexes due to the irritation of the mesencephalitis part of the reticular formation testifies to the fact of their inhibitive influence on these structures."} {"id": "PMID:1266496", "title": "[Comparative findings concerning the effect of elenium and seduxen on the cardiovascular system].", "content": "The authors studied the effect of seduxen and elenium on 169 patients, particularly their pulse frequency, arterial pressure, electro- and polycardiogramms in a single administration of the drugs parenterally and in a long-term per os administration. A parenteral introduction of both drugs was accompanied by a slight bradycardial effect. However, high doses of seduxen (0.34--0.5 mg/kg) lead to states of tachycardia. Unlike elenium which did not exert a hypotensive effect, seduxen displayed a mild and in some cases significant hypotensive action.", "contents": "[Comparative findings concerning the effect of elenium and seduxen on the cardiovascular system]. The authors studied the effect of seduxen and elenium on 169 patients, particularly their pulse frequency, arterial pressure, electro- and polycardiogramms in a single administration of the drugs parenterally and in a long-term per os administration. A parenteral introduction of both drugs was accompanied by a slight bradycardial effect. However, high doses of seduxen (0.34--0.5 mg/kg) lead to states of tachycardia. Unlike elenium which did not exert a hypotensive effect, seduxen displayed a mild and in some cases significant hypotensive action."} {"id": "PMID:1266498", "title": "[The clinical picture of acute epidural hematoma of traumatic origin].", "content": "An analysis of 100 observations permitted the authors to conclude that the basis of the clinical picture of acute epidural hematoma was the syndrome of intercranial hypertension manifesting itself in growing disturbances of consciousness, headaches, vomiting, bradycardia. The appearance of local neurological symptoms gives a possibility for a physician to orientate quickly in the pathological process localization. \"A lucid period\" and the initial syndrome of the acute brain dislocation often revealed in the manifestation of mydriase are typical of the clinical picture of epidural hematoma.", "contents": "[The clinical picture of acute epidural hematoma of traumatic origin]. An analysis of 100 observations permitted the authors to conclude that the basis of the clinical picture of acute epidural hematoma was the syndrome of intercranial hypertension manifesting itself in growing disturbances of consciousness, headaches, vomiting, bradycardia. The appearance of local neurological symptoms gives a possibility for a physician to orientate quickly in the pathological process localization. \"A lucid period\" and the initial syndrome of the acute brain dislocation often revealed in the manifestation of mydriase are typical of the clinical picture of epidural hematoma."} {"id": "PMID:1266499", "title": "[Peripheral microcirculatory disorders in severe cranio-cerebral injuries].", "content": "Photopletizmographical and capillaroscopic studies in 83 patients with severe brain trauma found a definite correlation between the character and localization of the brain lesion and peripheral microcirculation changes. The author considers that the data of the dynamical studies of the mentioned parameters can be significant for a judgement of the prognosis in severe brain traumas.", "contents": "[Peripheral microcirculatory disorders in severe cranio-cerebral injuries]. Photopletizmographical and capillaroscopic studies in 83 patients with severe brain trauma found a definite correlation between the character and localization of the brain lesion and peripheral microcirculation changes. The author considers that the data of the dynamical studies of the mentioned parameters can be significant for a judgement of the prognosis in severe brain traumas."} {"id": "PMID:1266500", "title": "[Cerebral hemodynamics in the acute and remote periods of closed cranio-cerebral trauma].", "content": "By using clinical and zonal REG methods the authors examined 204 patients with brain traumas. Such examinations permitted to detect symptoms of a disturbed cerebral vascular tone. In the acute period of a closed brain trauma changes of cerebral hemodynamics were not stable and were nonhomogenous by direction. A differential qualification of the general and cerebral hemodynamics in the remote period of a closed brain trauma permitted to distinguish 4 types of cerebral vascular disorders. The obtained results facilitate an objective assessment of brain traumas and their pathogenetical treatment.", "contents": "[Cerebral hemodynamics in the acute and remote periods of closed cranio-cerebral trauma]. By using clinical and zonal REG methods the authors examined 204 patients with brain traumas. Such examinations permitted to detect symptoms of a disturbed cerebral vascular tone. In the acute period of a closed brain trauma changes of cerebral hemodynamics were not stable and were nonhomogenous by direction. A differential qualification of the general and cerebral hemodynamics in the remote period of a closed brain trauma permitted to distinguish 4 types of cerebral vascular disorders. The obtained results facilitate an objective assessment of brain traumas and their pathogenetical treatment."} {"id": "PMID:1266502", "title": "[Clinico-electroencephalographic characteristics of the condition of brain stem systems following surgical and non-surgical brain injury].", "content": "The paper is concerned with a study of the stem structures in 186 patients during and following a removal of brain tumors and in 42 patients with acute brain traumas. A correlation of the EEG, the clinical picture and action of the central adreno- and cholinolytics and adrenomimetics demonstrated that in acute influences on the stem it is always in an irritative state. A significant degree of stem structures irritation during its direct affection is accompanied by an appearance in the EEG of synchronized low forms of fluctuations and clinical symptoms of vegetative hyperergia. In such conditions, besides measures of normalizing the hemodynamics and CSF circulation it is necessary to use preparations of a central adreno- and cholinolytic action.", "contents": "[Clinico-electroencephalographic characteristics of the condition of brain stem systems following surgical and non-surgical brain injury]. The paper is concerned with a study of the stem structures in 186 patients during and following a removal of brain tumors and in 42 patients with acute brain traumas. A correlation of the EEG, the clinical picture and action of the central adreno- and cholinolytics and adrenomimetics demonstrated that in acute influences on the stem it is always in an irritative state. A significant degree of stem structures irritation during its direct affection is accompanied by an appearance in the EEG of synchronized low forms of fluctuations and clinical symptoms of vegetative hyperergia. In such conditions, besides measures of normalizing the hemodynamics and CSF circulation it is necessary to use preparations of a central adreno- and cholinolytic action."} {"id": "PMID:1266503", "title": "[Anti-brain antibodies in serum and cerebrospinal fluid following cranio-cerebral trauma].", "content": "The author evaluated the precipitating antibrain antibodies by the Hoigne' method in the blood serum of 292 patients and in the CSF of 194 patients with acute brain traumas. Accordingly 52 and 21 patients were studied in the remote period. Antibodies were revealed more frequently and for a longer period of time following severe damages and less frequently in mild forms. They could also be revealed in patients with residual symptoms of brain trauma. Antibodies were revealed in the CSF earlier, more frequently and for a longer period of time than in the blood sera. These data speak in favour of a probable local formation of antibrain antibodies.", "contents": "[Anti-brain antibodies in serum and cerebrospinal fluid following cranio-cerebral trauma]. The author evaluated the precipitating antibrain antibodies by the Hoigne' method in the blood serum of 292 patients and in the CSF of 194 patients with acute brain traumas. Accordingly 52 and 21 patients were studied in the remote period. Antibodies were revealed more frequently and for a longer period of time following severe damages and less frequently in mild forms. They could also be revealed in patients with residual symptoms of brain trauma. Antibodies were revealed in the CSF earlier, more frequently and for a longer period of time than in the blood sera. These data speak in favour of a probable local formation of antibrain antibodies."} {"id": "PMID:1266504", "title": "[The epidemiology of postconcussional hypotension].", "content": "The presentation deals with a study of 942 patients (males and females from 16-68 years of age) with sequelae of brain damage, checked up with the duration of the post-traumatic period from several months to 35 years. The author draws special attention to the influence of sex, age and the duration of the posttraumatical period on the frequency of postconcussional hypotension. The obtained results point to a high frequency of postconcussional hypotension in the different age and sex groups compared to that found in the general population in screening. The prevalence of hypotension among females was higher. With an increase of the postconcussional period in males there was a tendency towards an increase of hypotension.", "contents": "[The epidemiology of postconcussional hypotension]. The presentation deals with a study of 942 patients (males and females from 16-68 years of age) with sequelae of brain damage, checked up with the duration of the post-traumatic period from several months to 35 years. The author draws special attention to the influence of sex, age and the duration of the posttraumatical period on the frequency of postconcussional hypotension. The obtained results point to a high frequency of postconcussional hypotension in the different age and sex groups compared to that found in the general population in screening. The prevalence of hypotension among females was higher. With an increase of the postconcussional period in males there was a tendency towards an increase of hypotension."} {"id": "PMID:1266505", "title": "[An attempt to prognosticate the rehabilitation of patients who have sustained closed brain injury].", "content": "The authors studied at the early and remote stages of the disease the adaptational function of analyzers (visual, acoustic, olfactory) and constructive practical actions in 82 patients who had suffered from closed brain traumas in peace-time. The same studies were conducted in 59 patients with remote sequealae of brain injuries during the wartime (barotraumas) for comparison. The authors compared the results of the studies on patients with different outcomes of rehabilitation and different kinds of brain injury and depicted some indices and manifestations unfavourable or relatively favourable for a social and occupational prognosis.", "contents": "[An attempt to prognosticate the rehabilitation of patients who have sustained closed brain injury]. The authors studied at the early and remote stages of the disease the adaptational function of analyzers (visual, acoustic, olfactory) and constructive practical actions in 82 patients who had suffered from closed brain traumas in peace-time. The same studies were conducted in 59 patients with remote sequealae of brain injuries during the wartime (barotraumas) for comparison. The authors compared the results of the studies on patients with different outcomes of rehabilitation and different kinds of brain injury and depicted some indices and manifestations unfavourable or relatively favourable for a social and occupational prognosis."} {"id": "PMID:1266506", "title": "[The role of subcortical structures in the formation of a chronic cortical epileptogenic focus].", "content": "The authors studied the significance in the \"maturation\" of the cortical chronic experimental epileptogenic focus. The studies were conducted in rabbits with the use of registration methods of a summarized bioelectric activity and activation of subcortical formation by electric current. It was established that the activation of inhibitory structures in the preconvulsive period facilitated the inhibition of \"maturation\" of the initial-cortical epileptogenic focus and an easier development of the convulsive attack in comparison with the control group (without stimulation of subcortical nuclei), while the activation of generalizing formations lead to more severe convulsive attacks.", "contents": "[The role of subcortical structures in the formation of a chronic cortical epileptogenic focus]. The authors studied the significance in the \"maturation\" of the cortical chronic experimental epileptogenic focus. The studies were conducted in rabbits with the use of registration methods of a summarized bioelectric activity and activation of subcortical formation by electric current. It was established that the activation of inhibitory structures in the preconvulsive period facilitated the inhibition of \"maturation\" of the initial-cortical epileptogenic focus and an easier development of the convulsive attack in comparison with the control group (without stimulation of subcortical nuclei), while the activation of generalizing formations lead to more severe convulsive attacks."} {"id": "PMID:1266507", "title": "[Changes in the body's oxygen regime in hypothalamic syndromes under the influence of hypoxic mixtures].", "content": "A study of the oxygen regimen in the organism of patients with hypothalamic syndromes (vegetative, vascular and neuroendrocrino-metabolic) according to the Lauer and Kolchinskaya method demonstrated that an inhalation of hypoxic mixture containing 15% of oxygen leads to changes in the respiration indices. Such changes were related to circulation, oxygen parameters and indicated an increase of hypoxemia under the influence of this mixture and of a significant drop in the consumption of oxygen by the tissues. This may also speak in favour of an inhibition of activities in the compensatory and adaptational mechanisms. The most expressed inhibitive activity of such mechansims was seen in patients with hypotonic vetetative-vascular syndromes which is most likely connected with a drop of the tone in the neurohormonal system in this group of patients.", "contents": "[Changes in the body's oxygen regime in hypothalamic syndromes under the influence of hypoxic mixtures]. A study of the oxygen regimen in the organism of patients with hypothalamic syndromes (vegetative, vascular and neuroendrocrino-metabolic) according to the Lauer and Kolchinskaya method demonstrated that an inhalation of hypoxic mixture containing 15% of oxygen leads to changes in the respiration indices. Such changes were related to circulation, oxygen parameters and indicated an increase of hypoxemia under the influence of this mixture and of a significant drop in the consumption of oxygen by the tissues. This may also speak in favour of an inhibition of activities in the compensatory and adaptational mechanisms. The most expressed inhibitive activity of such mechansims was seen in patients with hypotonic vetetative-vascular syndromes which is most likely connected with a drop of the tone in the neurohormonal system in this group of patients."} {"id": "PMID:1266508", "title": "[Speech and perception in acoustic-mnestic aphasia].", "content": "In clinical practice of brain lesions one of the frequently encountered disorders is the so-called acoustico-mnestic form of temporal aphasia, which was first described by A.R. Luria. However, its nature and the mechansim of speech disorders in this form of aphasia are still not clear, despite the theortical and practical significance of this problem. The convened experiments have demonstrated that disorders of such forms of speech as nominating, repeating and understanding in acoustico-mnestic aphasia emerges from visual and acoustical perception and its complicated connections with speech. Disorders of nominative functions of speech are related mainly to defects in the visual sphere, disorders of repeating and partially understanding speech - with the narrowing of the volume of acoustical perception. A possible pathophysiological mechanism of such speech disorders may be a decrease in the brain activity which leads to a substitution of simultaneous processes of perception by successional ones.", "contents": "[Speech and perception in acoustic-mnestic aphasia]. In clinical practice of brain lesions one of the frequently encountered disorders is the so-called acoustico-mnestic form of temporal aphasia, which was first described by A.R. Luria. However, its nature and the mechansim of speech disorders in this form of aphasia are still not clear, despite the theortical and practical significance of this problem. The convened experiments have demonstrated that disorders of such forms of speech as nominating, repeating and understanding in acoustico-mnestic aphasia emerges from visual and acoustical perception and its complicated connections with speech. Disorders of nominative functions of speech are related mainly to defects in the visual sphere, disorders of repeating and partially understanding speech - with the narrowing of the volume of acoustical perception. A possible pathophysiological mechanism of such speech disorders may be a decrease in the brain activity which leads to a substitution of simultaneous processes of perception by successional ones."} {"id": "PMID:1266509", "title": "[The pathogenesis of the opticopyramidal syndrome in carotid artery occlusions].", "content": "The paper is concerned with the results of fluorescent angiographies of the eye fundus in 24 patients with occlusions of the carotid arteries verified by angiographic methods. A comparison of clinical data, cerebral and fluorescent angiography of the eye ground revealed in the majority of the patients visual disturbances and a retardation of retinal circulation. It is assumed that the insufficiency of retinal circulation may be one of the pathogenetical mechanisms in the development of the optico-pyramidal syndrome in occulusions of the carotid artery.", "contents": "[The pathogenesis of the opticopyramidal syndrome in carotid artery occlusions]. The paper is concerned with the results of fluorescent angiographies of the eye fundus in 24 patients with occlusions of the carotid arteries verified by angiographic methods. A comparison of clinical data, cerebral and fluorescent angiography of the eye ground revealed in the majority of the patients visual disturbances and a retardation of retinal circulation. It is assumed that the insufficiency of retinal circulation may be one of the pathogenetical mechanisms in the development of the optico-pyramidal syndrome in occulusions of the carotid artery."} {"id": "PMID:1266510", "title": "[Rheoencephalography in headache paroxysms of vascular origin and several therapeutic problems].", "content": "The author conducted a REG study of 68 patients who were referred to hospitals due to paroxysmal headaches of a vascular genesis. Changes characteristic of attacks of headaches with phasic cerebral disturbances were revealed. The results of such studies were used for prescribing rational therapy and for the assessment of the working capacity of these patients.", "contents": "[Rheoencephalography in headache paroxysms of vascular origin and several therapeutic problems]. The author conducted a REG study of 68 patients who were referred to hospitals due to paroxysmal headaches of a vascular genesis. Changes characteristic of attacks of headaches with phasic cerebral disturbances were revealed. The results of such studies were used for prescribing rational therapy and for the assessment of the working capacity of these patients."} {"id": "PMID:1266511", "title": "[The functional state of the sympathetic-adrenal system and blood coagulation in transitory cerebral circulatory disorders].", "content": "The authors studied adrenalin and noradrenalin excretion with the diurnal urine and the state of hemocoagulation in 63 patients with transient disturbances of the brain circulation. A reliable increase of adrenalin excretion, a decrease of noradrenalin and an expressed activation of hemocoagulation were established. The extent of the functional state changes of the sympathetico-adrenal system varied according to etiology of brain circulation disturbances. A close relationship between indices of the sympathetico-adrenal system and the hemocoagulation process was found.", "contents": "[The functional state of the sympathetic-adrenal system and blood coagulation in transitory cerebral circulatory disorders]. The authors studied adrenalin and noradrenalin excretion with the diurnal urine and the state of hemocoagulation in 63 patients with transient disturbances of the brain circulation. A reliable increase of adrenalin excretion, a decrease of noradrenalin and an expressed activation of hemocoagulation were established. The extent of the functional state changes of the sympathetico-adrenal system varied according to etiology of brain circulation disturbances. A close relationship between indices of the sympathetico-adrenal system and the hemocoagulation process was found."} {"id": "PMID:1266512", "title": "[Hallucinosis of advanced age].", "content": "The author studied different hallucinosis seen in patients of old age. By the clinical expression these hallucinoses were unlike the known forms of endogenous and exogenous psychoses and had no signs of cerebral organic destructive age changes. It was demonstrated that the different hallucinosis according to the organs of sense have some common signs: the character of correlations between hallucinosis and the petty delusions of persecution and prejudice; the correlation between perceptive illusions and lesions of the peripheral receptor apparatus; the possibility of a transformation of one type of hallucinosis into another; a common character of hereditary loading. The studied hallucinosis were attributed by the author to a group of functional psychoses of old age.", "contents": "[Hallucinosis of advanced age]. The author studied different hallucinosis seen in patients of old age. By the clinical expression these hallucinoses were unlike the known forms of endogenous and exogenous psychoses and had no signs of cerebral organic destructive age changes. It was demonstrated that the different hallucinosis according to the organs of sense have some common signs: the character of correlations between hallucinosis and the petty delusions of persecution and prejudice; the correlation between perceptive illusions and lesions of the peripheral receptor apparatus; the possibility of a transformation of one type of hallucinosis into another; a common character of hereditary loading. The studied hallucinosis were attributed by the author to a group of functional psychoses of old age."} {"id": "PMID:1266513", "title": "[Suicide attempts in the involutional and aged periods].", "content": "The authors studied 76 patients from 51-87 years who attempted to commit suicide. The main diagnostic categories were involutional, senile and reactive psychoses, alcoholism, and schizophrenia. The main syndromes during which such acts were attempted were anxious-depressive, depressive-hypochondriacal and depressive-delusional. The formation of suicidal tendency was precipitated by age involution, somatical disorders, psychogenic traumas. In most of the patients following the suicidal attempt, there were mental disorders, conditioned both by the main psychic disturbance and by the personality reaction to the suicidal act, due to which special psychiatric treatment was necessary.", "contents": "[Suicide attempts in the involutional and aged periods]. The authors studied 76 patients from 51-87 years who attempted to commit suicide. The main diagnostic categories were involutional, senile and reactive psychoses, alcoholism, and schizophrenia. The main syndromes during which such acts were attempted were anxious-depressive, depressive-hypochondriacal and depressive-delusional. The formation of suicidal tendency was precipitated by age involution, somatical disorders, psychogenic traumas. In most of the patients following the suicidal attempt, there were mental disorders, conditioned both by the main psychic disturbance and by the personality reaction to the suicidal act, due to which special psychiatric treatment was necessary."} {"id": "PMID:1266514", "title": "[Skin temperature topography and the thermoreflex in atherosclerotic psychosis].", "content": "The author conducted a dynamic measurement of skin temperature and the neurovascular reflex in 179 patients with atherosclerotic psychoses. It was possible to eliminate a new diagnostical index which was named by the author as an index of skin-temperature asymmetry. It was established that the skin temperature in such mental disorders is 2-3 degrees lower than in normals while the index of skin-temperature asymmetry is 3-4 times more than in normals and the neurovascular reflex is weakened.", "contents": "[Skin temperature topography and the thermoreflex in atherosclerotic psychosis]. The author conducted a dynamic measurement of skin temperature and the neurovascular reflex in 179 patients with atherosclerotic psychoses. It was possible to eliminate a new diagnostical index which was named by the author as an index of skin-temperature asymmetry. It was established that the skin temperature in such mental disorders is 2-3 degrees lower than in normals while the index of skin-temperature asymmetry is 3-4 times more than in normals and the neurovascular reflex is weakened."} {"id": "PMID:1266515", "title": "[The XYY syndrome (brief clinico-morphologic characteristics)].", "content": "The authors conducted a cytogenetical, anthropological and clinical study of 5 patients with aneuromia by Y chromosome. A cytogenetical study of 4 patients revealed Kariotype 47, XYY, in one-mosaicism of the 46, XY/47, XYY type. All the patients had drive pathology, and a retarded intellect compared to normal individuals. According to the morphological signs the patients had the following common traits: an increased variability of the mandibular part of the face, a high nose bridge, acne vulgaris. It was also demonstrated that there was a tendency toward a longer body, length of hands. In 3 tall patients there was eunuchoid body built. In one of the patients the structure of the molars corresponded to such of fossil hominids.", "contents": "[The XYY syndrome (brief clinico-morphologic characteristics)]. The authors conducted a cytogenetical, anthropological and clinical study of 5 patients with aneuromia by Y chromosome. A cytogenetical study of 4 patients revealed Kariotype 47, XYY, in one-mosaicism of the 46, XY/47, XYY type. All the patients had drive pathology, and a retarded intellect compared to normal individuals. According to the morphological signs the patients had the following common traits: an increased variability of the mandibular part of the face, a high nose bridge, acne vulgaris. It was also demonstrated that there was a tendency toward a longer body, length of hands. In 3 tall patients there was eunuchoid body built. In one of the patients the structure of the molars corresponded to such of fossil hominids."} {"id": "PMID:1266517", "title": "[A clinical, \u00e9lectro\u00e9ncephalographic and biochemical study of epileptic children and adolescents and their relatives].", "content": "The paper deals with the role of hereditary factors in the appearance of epilepsy by the aid of clinical, EEG and biochemical methods. The authors studied 35 children and adolescents with epilepsy and 69 of their relatives. In a EEG study fo the relatives of such patients there were 56% of changed curves, which indicate to an increased readiness of the brain to paroxysmal states. Besides, in the group of relatives where the children had epilepsy of an unknown nature the amount of changed curves was higher than that in the group of relatives where the patients had symptomatical epilepsy (62% and 51%). The biochemical data demonstrated some correlations between the bioelectrical brain activity with an increased amount of isoenzyme and LDH-I in the blood sera of relatives of epileptic patients.", "contents": "[A clinical, \u00e9lectro\u00e9ncephalographic and biochemical study of epileptic children and adolescents and their relatives]. The paper deals with the role of hereditary factors in the appearance of epilepsy by the aid of clinical, EEG and biochemical methods. The authors studied 35 children and adolescents with epilepsy and 69 of their relatives. In a EEG study fo the relatives of such patients there were 56% of changed curves, which indicate to an increased readiness of the brain to paroxysmal states. Besides, in the group of relatives where the children had epilepsy of an unknown nature the amount of changed curves was higher than that in the group of relatives where the patients had symptomatical epilepsy (62% and 51%). The biochemical data demonstrated some correlations between the bioelectrical brain activity with an increased amount of isoenzyme and LDH-I in the blood sera of relatives of epileptic patients."} {"id": "PMID:1266518", "title": "[Clinico-pathophysiologic aspects of a study of the hereditary predisposition of children and adolescents to epilepsy].", "content": "In a clinical, genealogical, biochemical, immunological and EEG study of children and adolescents with epilepsy and their closest relatives, it was established that the general activity of lactate dehydrogenase and the % of LDH in the blood sera of probands is higher than in normals. These changes were more expressed in the blood sera of probands and sibs, rather than in parents. The coefficient of inheritance according to both biochemical indices for probands and their relatives was approximately 80-85%. There were no differences in relation to the biological indices between epilepsy of an unknown nature and a symptomatical genesis.", "contents": "[Clinico-pathophysiologic aspects of a study of the hereditary predisposition of children and adolescents to epilepsy]. In a clinical, genealogical, biochemical, immunological and EEG study of children and adolescents with epilepsy and their closest relatives, it was established that the general activity of lactate dehydrogenase and the % of LDH in the blood sera of probands is higher than in normals. These changes were more expressed in the blood sera of probands and sibs, rather than in parents. The coefficient of inheritance according to both biochemical indices for probands and their relatives was approximately 80-85%. There were no differences in relation to the biological indices between epilepsy of an unknown nature and a symptomatical genesis."} {"id": "PMID:1266519", "title": "[Deontologic aspects of the problem of rehabilitating patients cured of epilepsy in childhood].", "content": "The authors followed-up 720 epileptic children who were previously treated in hospitals. The duration of follow-up was from 5-20 years. It was established that at the moment of the study 43.2% of the observed contingent were practically healthy. Criteria are given which in the opinion of the authors indicate to full recovery. They object to any restrictions in relation to employment and education of fully recovered patients and consider that indications working activity and studies for epileptic patients should be broadened. Special wards, sanatoria and forest schools should be opened for epileptic patients. Great attention should be drawn to the work with the parents of ill children.", "contents": "[Deontologic aspects of the problem of rehabilitating patients cured of epilepsy in childhood]. The authors followed-up 720 epileptic children who were previously treated in hospitals. The duration of follow-up was from 5-20 years. It was established that at the moment of the study 43.2% of the observed contingent were practically healthy. Criteria are given which in the opinion of the authors indicate to full recovery. They object to any restrictions in relation to employment and education of fully recovered patients and consider that indications working activity and studies for epileptic patients should be broadened. Special wards, sanatoria and forest schools should be opened for epileptic patients. Great attention should be drawn to the work with the parents of ill children."} {"id": "PMID:1266520", "title": "[Dynamics of the clinico-pathophysiologic characteristics of psychoses in old age under the influence of azafen].", "content": "A study of singular doses and subsequent maintenance therapy by azafen on the higher nervous activity of mental patients in presenile age (67 cases) revealed that its action depends upon the dosage of the preparation and the nosological syndrome. A depressive involutional psychoses can be controlled by azafen in doses up to 75 mg daily. By dosages of 25 mg azafen reduces or cessates completely the syndrome of changed consciousness due to disorders of brain circulation. An arrest of a depressive syndrome in manic-depressive psychosis in old age can be attained by an introduction of 150-200 mg of azafen daily.", "contents": "[Dynamics of the clinico-pathophysiologic characteristics of psychoses in old age under the influence of azafen]. A study of singular doses and subsequent maintenance therapy by azafen on the higher nervous activity of mental patients in presenile age (67 cases) revealed that its action depends upon the dosage of the preparation and the nosological syndrome. A depressive involutional psychoses can be controlled by azafen in doses up to 75 mg daily. By dosages of 25 mg azafen reduces or cessates completely the syndrome of changed consciousness due to disorders of brain circulation. An arrest of a depressive syndrome in manic-depressive psychosis in old age can be attained by an introduction of 150-200 mg of azafen daily."} {"id": "PMID:1266521", "title": "[Electrosleep and rhythmotherapeutic sleep].", "content": "The paper is a summary of the therapeutical effectiveness of rhythmotherapeutical sleep in some neuropsychic and neurosomatic disorders. During 8 years of approbation of this method 740 patients (adults and children) received such treatment. The positive therapeutical effect seen in more than than 80% of the cases permits to highly estimate this method and the apparatus (LIDA) used for these purposes.", "contents": "[Electrosleep and rhythmotherapeutic sleep]. The paper is a summary of the therapeutical effectiveness of rhythmotherapeutical sleep in some neuropsychic and neurosomatic disorders. During 8 years of approbation of this method 740 patients (adults and children) received such treatment. The positive therapeutical effect seen in more than than 80% of the cases permits to highly estimate this method and the apparatus (LIDA) used for these purposes."} {"id": "PMID:1266522", "title": "[Correlation between the anticonvulsant and tranquilizing effects of carbamazepine and methindione in experimental temporal epilepsy].", "content": "In 16 rabbits with chronic implanted electrodes the authors convened an electrostimulation of the hypocampus, the amygdale body and new cortex which brought to emotional-affective and EEG convulsive reactions. These reactions were inhibited by karbamazepine (150 mg/kg) and methindion (100 and 200 mg/kg) introduced into the gastrum. Karbamazepine possessed most inhibiting effect. The tranquillizing effect of methindion exceedes its anticonvulsive action, due to which it can be used both as an anticonvulsant and tranquilizing preparation. For this reason its combined effect should be most effective in temporal epilepsy.", "contents": "[Correlation between the anticonvulsant and tranquilizing effects of carbamazepine and methindione in experimental temporal epilepsy]. In 16 rabbits with chronic implanted electrodes the authors convened an electrostimulation of the hypocampus, the amygdale body and new cortex which brought to emotional-affective and EEG convulsive reactions. These reactions were inhibited by karbamazepine (150 mg/kg) and methindion (100 and 200 mg/kg) introduced into the gastrum. Karbamazepine possessed most inhibiting effect. The tranquillizing effect of methindion exceedes its anticonvulsive action, due to which it can be used both as an anticonvulsant and tranquilizing preparation. For this reason its combined effect should be most effective in temporal epilepsy."} {"id": "PMID:1266523", "title": "[An adverse glycemic effect in patients as a result of treatment with neuroleptics].", "content": "A study of reasons leading to complications in a combined treatment by insulin and neuroleptocal drugs of schizophrenic patients demonstrated that neuroleptical preparations have certain properties acting in some case on a drop of sugar in the blood. It was depicted as well that neuroleptical drugs have a latent side-effect and affect the sugar metabolism. In a long-term use of these preparations the sugar curves correspond to a latent and clinically expressed diabetes. Cases of diabetes among the mental patients are as a rule a result of a long-term action of neuroleptical drugs.", "contents": "[An adverse glycemic effect in patients as a result of treatment with neuroleptics]. A study of reasons leading to complications in a combined treatment by insulin and neuroleptocal drugs of schizophrenic patients demonstrated that neuroleptical preparations have certain properties acting in some case on a drop of sugar in the blood. It was depicted as well that neuroleptical drugs have a latent side-effect and affect the sugar metabolism. In a long-term use of these preparations the sugar curves correspond to a latent and clinically expressed diabetes. Cases of diabetes among the mental patients are as a rule a result of a long-term action of neuroleptical drugs."} {"id": "PMID:1266524", "title": "Decarboxylation of S-adenosyl-L-methionine in vitamin B6 deficiency in rat liver.", "content": "The effect of a prolonged diet deficient in B6-vitamin on the activity of adenosylmethionine decarboxylase from rat liver was investigated. In contrast to an earlier report, 12 adenosylmethionine decarboxylase activity was not found to be decreased under these restricted nutritional conditions. Moreover, the addition of pyridoxal phosphate into the standard incubation mixture did not stimulate the activity of adenosylmethionine decarboxylase from the livers of the rats fed the B6-vitamin deficient diet. It is suggested that the contradictory results of Sturman and Kremzner12 might be based on an artificial liberation of carbon dioxide from S-adenosyl-L-methionine in the presence of pyridoxal phosphate. The results of this communication do not support the view that pyridoxal phosphate acts as the prosthetic group of rat liver adenosylmethionine decarboxylase.", "contents": "Decarboxylation of S-adenosyl-L-methionine in vitamin B6 deficiency in rat liver. The effect of a prolonged diet deficient in B6-vitamin on the activity of adenosylmethionine decarboxylase from rat liver was investigated. In contrast to an earlier report, 12 adenosylmethionine decarboxylase activity was not found to be decreased under these restricted nutritional conditions. Moreover, the addition of pyridoxal phosphate into the standard incubation mixture did not stimulate the activity of adenosylmethionine decarboxylase from the livers of the rats fed the B6-vitamin deficient diet. It is suggested that the contradictory results of Sturman and Kremzner12 might be based on an artificial liberation of carbon dioxide from S-adenosyl-L-methionine in the presence of pyridoxal phosphate. The results of this communication do not support the view that pyridoxal phosphate acts as the prosthetic group of rat liver adenosylmethionine decarboxylase."} {"id": "PMID:1266525", "title": "Thermal properties of systems containing cholesteryl esters and triglycerides.", "content": "Binary and ternary systems of the three cholesteryl esters, linoleate, oleate, and stearate and the two triglycerides, triolein and tristearin were studied in order to determine the phase transitions and the conditions for the cholesteric and smectic mesophases. Phase transitions were determined using differential thermal analysis, melting point determination, and polarizing microscopy. Of the cholesterol esters the linoleate-oleate system showed complete miscibility in both the liquid and solid phases. The linoleate-stearate and oleate-stearate systems are of the eutectic type with limited solid solubility. The mesophases are monotropic as to the crystalline state and exist over the entire composition interval in all cholesteryl ester systems studied.", "contents": "Thermal properties of systems containing cholesteryl esters and triglycerides. Binary and ternary systems of the three cholesteryl esters, linoleate, oleate, and stearate and the two triglycerides, triolein and tristearin were studied in order to determine the phase transitions and the conditions for the cholesteric and smectic mesophases. Phase transitions were determined using differential thermal analysis, melting point determination, and polarizing microscopy. Of the cholesterol esters the linoleate-oleate system showed complete miscibility in both the liquid and solid phases. The linoleate-stearate and oleate-stearate systems are of the eutectic type with limited solid solubility. The mesophases are monotropic as to the crystalline state and exist over the entire composition interval in all cholesteryl ester systems studied."} {"id": "PMID:1266526", "title": "Crystal structures of synthetic analgetics. V. Dextromoramide.", "content": "The molecular and crystal structure of dextromoramide has been determined by X-ray methods. The crystals are orthorhombic, space group P212121 with unit cell dimensions a = 9.720(4) A; b = 12.226(3) A; c = 18.381(3) A. The structure was determined by direct methods and the model refined to an R-value of 0.036 for 1788 observed reflections. The mean e.s.d.'s in bond lengths and angles are 0.004 A and 0.3, respectively. The morpholine moiety is nearly in antiposition relative to the quaternary carbon atom C6, the pertinent angle C6 - C7 - C9 - N2 being - 159.4. This conformation is similar to that previously reported for the bitartrate of the title compound. The pyrrolidine ring has the envelope conformation and the amide group is strictly planar. The conformation of some acyclic analgetics are discussed.", "contents": "Crystal structures of synthetic analgetics. V. Dextromoramide. The molecular and crystal structure of dextromoramide has been determined by X-ray methods. The crystals are orthorhombic, space group P212121 with unit cell dimensions a = 9.720(4) A; b = 12.226(3) A; c = 18.381(3) A. The structure was determined by direct methods and the model refined to an R-value of 0.036 for 1788 observed reflections. The mean e.s.d.'s in bond lengths and angles are 0.004 A and 0.3, respectively. The morpholine moiety is nearly in antiposition relative to the quaternary carbon atom C6, the pertinent angle C6 - C7 - C9 - N2 being - 159.4. This conformation is similar to that previously reported for the bitartrate of the title compound. The pyrrolidine ring has the envelope conformation and the amide group is strictly planar. The conformation of some acyclic analgetics are discussed."} {"id": "PMID:1266536", "title": "Tensile strengths of twelve types of knot employed in surgery, using different suture materials.", "content": "When knotted loops of suture material were subjected to increasing tensile stress it was the knot that gave way in 710 of 720 experiments. The knot is thus the weakest point in the loop. A new code for describing knots useful in surgery has been worked out. The tensile strength of 12 different knots using twelve different suture materials with the dimension 3/0 (USP) was examined systematically. It was found that the efficiency of the knots varied depending upon the tensile strength of the material, 5% for the weakest and 99% for the strongest knot-material combination. Monofil and multifil steel threads were superior to other materials examined with regard to the knot strength. Chromic and plain catgut showed at least 50% of the tensile strength of the corresponding thread, irrespective of the type of knot. Silk was among the materials which gave the weakest knots. In principle, the more turns and throws the stronger the knot.", "contents": "Tensile strengths of twelve types of knot employed in surgery, using different suture materials. When knotted loops of suture material were subjected to increasing tensile stress it was the knot that gave way in 710 of 720 experiments. The knot is thus the weakest point in the loop. A new code for describing knots useful in surgery has been worked out. The tensile strength of 12 different knots using twelve different suture materials with the dimension 3/0 (USP) was examined systematically. It was found that the efficiency of the knots varied depending upon the tensile strength of the material, 5% for the weakest and 99% for the strongest knot-material combination. Monofil and multifil steel threads were superior to other materials examined with regard to the knot strength. Chromic and plain catgut showed at least 50% of the tensile strength of the corresponding thread, irrespective of the type of knot. Silk was among the materials which gave the weakest knots. In principle, the more turns and throws the stronger the knot."} {"id": "PMID:1266537", "title": "Pulmonary damage following pulmonary microembolism in the dog. Effect of various types of treatment.", "content": "In the present study the pathogenesis of the pulmonary damage following infusion of thrombin in combination with a fibrinolysis inhibitor, AMCA, in the dog was elucidated. An important mechanism in the development of the pulmonary damage following infusion of thrombin and AMCA seems to be an increased vascular permeability in the pulmonary microvasculature leading to pulmonary oedema. The question whether this pulmonary damage can be prevented by antihistamine (mepyramine maleate), antiserotonins (methysergide, reserpine) antiprostaglandins (acetylsalicylic acid, indomethacin, polyphloretin phosphate), 'anti-inflammatory agents' (methylprednisolone, calcium) or an anti-adrenergic agent (phenoxybenzamine) was investigated. None of these agents did prevent the lung damage following thrombin and AMCA. In order to study the possible role of bronchoconstriction, the complement system and the kinin system for this damage dogs were also artificially ventilated with an increased end-expiratory pressure, decomplemented with cobra venom factor or treated with Trasylol respectively. Neither were these treatments effective in preventing the pulmonary damage. The findings of the present study suggest that the permeability increasing substance involved in the pathogenesis of the pulmonary damage following thrombin and AMCA is not histamine, serotonin, prostaglandins or bradykinin. Therefore another, still unknown factor, may be of greater importance for this damage.", "contents": "Pulmonary damage following pulmonary microembolism in the dog. Effect of various types of treatment. In the present study the pathogenesis of the pulmonary damage following infusion of thrombin in combination with a fibrinolysis inhibitor, AMCA, in the dog was elucidated. An important mechanism in the development of the pulmonary damage following infusion of thrombin and AMCA seems to be an increased vascular permeability in the pulmonary microvasculature leading to pulmonary oedema. The question whether this pulmonary damage can be prevented by antihistamine (mepyramine maleate), antiserotonins (methysergide, reserpine) antiprostaglandins (acetylsalicylic acid, indomethacin, polyphloretin phosphate), 'anti-inflammatory agents' (methylprednisolone, calcium) or an anti-adrenergic agent (phenoxybenzamine) was investigated. None of these agents did prevent the lung damage following thrombin and AMCA. In order to study the possible role of bronchoconstriction, the complement system and the kinin system for this damage dogs were also artificially ventilated with an increased end-expiratory pressure, decomplemented with cobra venom factor or treated with Trasylol respectively. Neither were these treatments effective in preventing the pulmonary damage. The findings of the present study suggest that the permeability increasing substance involved in the pathogenesis of the pulmonary damage following thrombin and AMCA is not histamine, serotonin, prostaglandins or bradykinin. Therefore another, still unknown factor, may be of greater importance for this damage."} {"id": "PMID:1266538", "title": "Induction of endogenous fibrinolysis inhibition in the dog. Effect of intravascular coagulation and release of free fatty acids.", "content": "Possible mechanisms underlying the development of fibrinolysis inhibition following trauma were studied. In order to investigate the role of intravascular coagulation dogs were subjected to infusions of thrombin or endotoxin, which both caused an increase in urokinase inhibitor activity in serum after 24 and 48 hours. The inhibitor increase following thrombin infusion was not, however, prevented by previous defibrinogenation with Defibrase or by induction of thrombocytopenia with antiplatelet serum, suggesting that neither platelets nor fibrinogen are necessary for the post-traumatic occurrence of fibrinolysis inhibition. In all groups subjected to infusion of thrombin an increase in plasma free fatty acids (FFA) was observed. The role of this increase for the development of fibrinolysis inhibition was tested by infusion of norepinephrine alone and in combination with nicotinic acid. Norepinephrine caused an increase of FFA after 2 hours and in urokinase inhibitor activity after 24-48 hours. Both of these were diminished by high doses of nicotinic acid, indicating that the release of FFA rather than intravascular coagulation might be the principal mechanism underlying the occurrence of fibrinolysis inhibition following trauma.", "contents": "Induction of endogenous fibrinolysis inhibition in the dog. Effect of intravascular coagulation and release of free fatty acids. Possible mechanisms underlying the development of fibrinolysis inhibition following trauma were studied. In order to investigate the role of intravascular coagulation dogs were subjected to infusions of thrombin or endotoxin, which both caused an increase in urokinase inhibitor activity in serum after 24 and 48 hours. The inhibitor increase following thrombin infusion was not, however, prevented by previous defibrinogenation with Defibrase or by induction of thrombocytopenia with antiplatelet serum, suggesting that neither platelets nor fibrinogen are necessary for the post-traumatic occurrence of fibrinolysis inhibition. In all groups subjected to infusion of thrombin an increase in plasma free fatty acids (FFA) was observed. The role of this increase for the development of fibrinolysis inhibition was tested by infusion of norepinephrine alone and in combination with nicotinic acid. Norepinephrine caused an increase of FFA after 2 hours and in urokinase inhibitor activity after 24-48 hours. Both of these were diminished by high doses of nicotinic acid, indicating that the release of FFA rather than intravascular coagulation might be the principal mechanism underlying the occurrence of fibrinolysis inhibition following trauma."} {"id": "PMID:1266539", "title": "Heme compounds in the plasma in small bowel ischemia in the rat.", "content": "The early diagnosis of acute mesenteric occlusion presents a difficult problem in abdominal surgery. In a study on rats the relation between graded small bowel ischemia and the concentration of heme compounds in the plasma was investigated. The ischemia was produced by ligation of terminal vessels at the mesenteric margin of the intestine (mesenteric end arcades) or the superior mesenteric artery. Heme compounds were assayed by a benzidine method developed by Crossby et al. The concentration of heme compounds in the plasma was higher in animals with various grades of intestinal ischemia than in animals subjected to laparotomy alone. This increase was noted as early as 4 hours after induction of moderate and severe grade of ischemia. The results indicate that an increase in plasma concentration of heme compounds takes place at an early stage of moderate and severe small bowel ischemia following mesenteric vascular occlusion but not until after 48 hours in mild ischemia. The clinical value of this method has to be tested in a clinical study.", "contents": "Heme compounds in the plasma in small bowel ischemia in the rat. The early diagnosis of acute mesenteric occlusion presents a difficult problem in abdominal surgery. In a study on rats the relation between graded small bowel ischemia and the concentration of heme compounds in the plasma was investigated. The ischemia was produced by ligation of terminal vessels at the mesenteric margin of the intestine (mesenteric end arcades) or the superior mesenteric artery. Heme compounds were assayed by a benzidine method developed by Crossby et al. The concentration of heme compounds in the plasma was higher in animals with various grades of intestinal ischemia than in animals subjected to laparotomy alone. This increase was noted as early as 4 hours after induction of moderate and severe grade of ischemia. The results indicate that an increase in plasma concentration of heme compounds takes place at an early stage of moderate and severe small bowel ischemia following mesenteric vascular occlusion but not until after 48 hours in mild ischemia. The clinical value of this method has to be tested in a clinical study."} {"id": "PMID:1266540", "title": "Vasopressin tachyphylaxis. A study in conscious man.", "content": "The effects of repeated intravenous constant infusion of lysine-8-vasopressin (LVP) in a series of 12 conscious patients with portal venous catheters were studied. The portal venous pressure fell, the arterio-portal venous oxygen difference and the systolic and diastolic blood pressures rose and the heart rate decreased. Although no signs of tachyphylaxis were seen in portal venous pressure, systolic blood pressure or heart rate, they were observed both in the arterio-portal venous oxygen difference, indicating a tachyphylactic reaction in the effects on splanchnic blood flow, and in the diastolic blood pressure.", "contents": "Vasopressin tachyphylaxis. A study in conscious man. The effects of repeated intravenous constant infusion of lysine-8-vasopressin (LVP) in a series of 12 conscious patients with portal venous catheters were studied. The portal venous pressure fell, the arterio-portal venous oxygen difference and the systolic and diastolic blood pressures rose and the heart rate decreased. Although no signs of tachyphylaxis were seen in portal venous pressure, systolic blood pressure or heart rate, they were observed both in the arterio-portal venous oxygen difference, indicating a tachyphylactic reaction in the effects on splanchnic blood flow, and in the diastolic blood pressure."} {"id": "PMID:1266541", "title": "Effect of vasopressin on regional splanchnic blood flows in conscious man.", "content": "In 11 conscious normovolaemic patients with acute or chronic pancreatitis the effect of a continuous intravenous infusion of lysine-8-vasopressin, 5 IU/70 kg b.w./20 min on the portal and the hepatic venous blood flows was studied by using multiple portal catheters, oxygen saturation measurements and an indicator dilution technique with continuous infusion of 133Xe into the portal vein or its tributaries. During vasopressin infusion the total hepatic blood flow, estimated by the Bradley technique with indocyanine green dye, was reduced to 61% of the value at rest. Owing to the simultaneously occurring streamlining of the portal venous flow with incomplete mixing of indicator and blood, the portal and hepatic venous blood flows could be measured in only 3 of 9 patients. The reduction in the portal venous blood flow during vasopressin infusion was more marked than the decrease of the total hepatic flow, corresponding to a calculated increase of the hepatic arterial flow of 50%. Total splanchnic oxygen uptake and extrahepatic splanchnic oxygen uptake were unchanged during and after infusion of vasopressin. Thus, changes in splandhnic blood flow could be estimated from changes in arteriovenous oxygen differences. Also by this method a more pronounced reduction in the portal venous than of the hepatic venous blood flow was observed. The decrease during vasopressin infusion of the superior mesenteric venous flow was more marked than that of the splenic vein. The splanchnic circulatory changes may be different for other doses of vasopressin and in cirrhotic patients with higher hepatic arterial blood flow fractions.", "contents": "Effect of vasopressin on regional splanchnic blood flows in conscious man. In 11 conscious normovolaemic patients with acute or chronic pancreatitis the effect of a continuous intravenous infusion of lysine-8-vasopressin, 5 IU/70 kg b.w./20 min on the portal and the hepatic venous blood flows was studied by using multiple portal catheters, oxygen saturation measurements and an indicator dilution technique with continuous infusion of 133Xe into the portal vein or its tributaries. During vasopressin infusion the total hepatic blood flow, estimated by the Bradley technique with indocyanine green dye, was reduced to 61% of the value at rest. Owing to the simultaneously occurring streamlining of the portal venous flow with incomplete mixing of indicator and blood, the portal and hepatic venous blood flows could be measured in only 3 of 9 patients. The reduction in the portal venous blood flow during vasopressin infusion was more marked than the decrease of the total hepatic flow, corresponding to a calculated increase of the hepatic arterial flow of 50%. Total splanchnic oxygen uptake and extrahepatic splanchnic oxygen uptake were unchanged during and after infusion of vasopressin. Thus, changes in splandhnic blood flow could be estimated from changes in arteriovenous oxygen differences. Also by this method a more pronounced reduction in the portal venous than of the hepatic venous blood flow was observed. The decrease during vasopressin infusion of the superior mesenteric venous flow was more marked than that of the splenic vein. The splanchnic circulatory changes may be different for other doses of vasopressin and in cirrhotic patients with higher hepatic arterial blood flow fractions."} {"id": "PMID:1266542", "title": "The effect of glucagon on total liver blood flow after occlusion of the hepatic artery. A study in anesthetized, normotensive dogs.", "content": "It has earlier been shown that the hormone glucagon has the property of increasing liver blood flow both in normotensive dogs as well as in dogs in hemorrhagic shock. This study was done to evaluate the effect of glucagon given in normotensive dogs after occlusion of the hepatic artery. Glucagon was given in a single dose of 50 mug/kg bodyweight. The study shows that glucagon under these circumstances increased total liver blood flow 67% compared to an increase of 3% in a control group. The increase is statistically significant compared to the effect of placebo injection in a control group. A benefit of the hormone is suggested in man in surgical situation where occlusion of the hepatic artery becomes necessary.", "contents": "The effect of glucagon on total liver blood flow after occlusion of the hepatic artery. A study in anesthetized, normotensive dogs. It has earlier been shown that the hormone glucagon has the property of increasing liver blood flow both in normotensive dogs as well as in dogs in hemorrhagic shock. This study was done to evaluate the effect of glucagon given in normotensive dogs after occlusion of the hepatic artery. Glucagon was given in a single dose of 50 mug/kg bodyweight. The study shows that glucagon under these circumstances increased total liver blood flow 67% compared to an increase of 3% in a control group. The increase is statistically significant compared to the effect of placebo injection in a control group. A benefit of the hormone is suggested in man in surgical situation where occlusion of the hepatic artery becomes necessary."} {"id": "PMID:1266543", "title": "Healing of a crush injury in rat striated muscle. 4. Effect of early mobilization and immobilization on the tensile properties of gastrocnemius muscle.", "content": "Tensile properties of partially crushed gastrocnemius muscle were studied and compared with the uninjured control muscles of 185 rats after treatment by mobilization on the treadmill or immobilization in a softened plaster cast. Two to 42 days after a reproducible injury induced to the left calf of the rat, load-deformation curves were registered from both gastrocnemius muslce and several parameters were assessed from the curves. The rupture site was studied macroscopically as well as histologically. In injured muscles the rupture was usually observed at or near to the injury (92%) when in intact muscles the rupture most often (94%) occurred at the muscle belly. The decrease in breaking strength and energy absorption due to the injury was rather constant (20-25%) on day 2 after trauma. Thereafter in mobilized muscles these values, as well as those of elastic stiffness, returned to the level of the uninjured control muscles more rapidly than in immobilized muscles, where a decrease in tensile properties at the end of the first week was on an average 20-30% and fell still further to 30-40% towards the end of the immobilization period (21 days). Three weeks after the removal of the casts these values in the previously immobilized muscles had not yet reached the level of the controlateral control muscles.", "contents": "Healing of a crush injury in rat striated muscle. 4. Effect of early mobilization and immobilization on the tensile properties of gastrocnemius muscle. Tensile properties of partially crushed gastrocnemius muscle were studied and compared with the uninjured control muscles of 185 rats after treatment by mobilization on the treadmill or immobilization in a softened plaster cast. Two to 42 days after a reproducible injury induced to the left calf of the rat, load-deformation curves were registered from both gastrocnemius muslce and several parameters were assessed from the curves. The rupture site was studied macroscopically as well as histologically. In injured muscles the rupture was usually observed at or near to the injury (92%) when in intact muscles the rupture most often (94%) occurred at the muscle belly. The decrease in breaking strength and energy absorption due to the injury was rather constant (20-25%) on day 2 after trauma. Thereafter in mobilized muscles these values, as well as those of elastic stiffness, returned to the level of the uninjured control muscles more rapidly than in immobilized muscles, where a decrease in tensile properties at the end of the first week was on an average 20-30% and fell still further to 30-40% towards the end of the immobilization period (21 days). Three weeks after the removal of the casts these values in the previously immobilized muscles had not yet reached the level of the controlateral control muscles."} {"id": "PMID:1266544", "title": "Ideal cholecystectomy: in an early stage at an early age.", "content": "Two consecutive series of patients operated for gallstone disease were compared. One series emanated from a Swedish hospital in which an active surgical policy had been practised for many years while the other stemmed from a Swedish hospital in which the attitude towards surgery had been conservative. In this latter hospital there were more cases with biliary duct stones, especially hepatic duct stones. There were also more cases with jaundice, more cases with acute cholecystitis with high fever, more cases with protracted postoperative fever and with infection of the wound and more cases with a lengthy stay at the hospital. Responsible for all these differences were the older age groups. The conclusion is that the ideal treatment for gallstone disease is early operation, i.e. operation in an early stage and at an early age.", "contents": "Ideal cholecystectomy: in an early stage at an early age. Two consecutive series of patients operated for gallstone disease were compared. One series emanated from a Swedish hospital in which an active surgical policy had been practised for many years while the other stemmed from a Swedish hospital in which the attitude towards surgery had been conservative. In this latter hospital there were more cases with biliary duct stones, especially hepatic duct stones. There were also more cases with jaundice, more cases with acute cholecystitis with high fever, more cases with protracted postoperative fever and with infection of the wound and more cases with a lengthy stay at the hospital. Responsible for all these differences were the older age groups. The conclusion is that the ideal treatment for gallstone disease is early operation, i.e. operation in an early stage and at an early age."} {"id": "PMID:1266545", "title": "Carcinoma of the stomach. A ten-year material.", "content": "1959-68 220 patients from Aust-Agder County were admitted to the Central Hospital with carcinoma of the stomach. The material is analysed and discussed. The average age of the patients was 69.4 years. A palpable tumour was found in 96 patients (46%); of these 6 survived 5 years. A short case history is connected with a better prognosis. One hundred and forty-nine patients (71.3%) underwent laparotomy, and the tumour could be removed in 94 cases (45%). The standard treatment has been partial gastrectomy according to Billroth II. Better results can possibly be achieved if the diagnosis is made at an earlier stage, which means before the tumour causes classical symptoms. Early gastrectomy is recommended in cases of ulcer of the stomach or X-ray negative dyspepsia.", "contents": "Carcinoma of the stomach. A ten-year material. 1959-68 220 patients from Aust-Agder County were admitted to the Central Hospital with carcinoma of the stomach. The material is analysed and discussed. The average age of the patients was 69.4 years. A palpable tumour was found in 96 patients (46%); of these 6 survived 5 years. A short case history is connected with a better prognosis. One hundred and forty-nine patients (71.3%) underwent laparotomy, and the tumour could be removed in 94 cases (45%). The standard treatment has been partial gastrectomy according to Billroth II. Better results can possibly be achieved if the diagnosis is made at an earlier stage, which means before the tumour causes classical symptoms. Early gastrectomy is recommended in cases of ulcer of the stomach or X-ray negative dyspepsia."} {"id": "PMID:1266546", "title": "Pregnancy after jejuno-ileostomy because of obesity.", "content": "In four cases of pregnancy after jejuno-ileostomy because of massive obesity intestinal absorption was adequate for the nutrition of both the baby and the mother. It appears that such an operation because of obestiy does not contraindicate later pregnancy; In one case postoperative loss of body weight probably made pregnancy possible. In extremely adipose women who are for some unknown reason infertile and wish to have a child a shunt operation might perhaps be offered.", "contents": "Pregnancy after jejuno-ileostomy because of obesity. In four cases of pregnancy after jejuno-ileostomy because of massive obesity intestinal absorption was adequate for the nutrition of both the baby and the mother. It appears that such an operation because of obestiy does not contraindicate later pregnancy; In one case postoperative loss of body weight probably made pregnancy possible. In extremely adipose women who are for some unknown reason infertile and wish to have a child a shunt operation might perhaps be offered."} {"id": "PMID:1266547", "title": "Studies on Crohn's disease. 1. The relationship between Yersinia enterocolitica infection and terminal ileitis.", "content": "Patients with terminal ileitis or regional enterocolitis have been examined for signs of infection due to Yersinia enterocolitica serotype 3. The patients were grouped according to the length of preoperative history. Among 18 patients with preoperative symptoms of one week or less there were nine with positive signs of Yersinia enterocolitica infection. None of these patients developed the chronic form of Crohn's disease while two of the primarily Yersinia negative patients progressed to the chronic form. Among nine patients with preoperative symptoms of one week to three months there was one patient with positive signs of Yersinia enterocolitica infection. This patient has remained healthy whereas seven of the negative ones progressed to the chronic form of Crohn's disease. None of the patients with established Crohn's disease of the chronic form had signs of recent Yersinia infection. The findings indicate that patients with acute terminal ileitis and positive signs of Yersinia infection are not likely to progress to the chronic form of Crohn's disease. Bacteriologic and serologic investigation for Yersinia infection are therefore of prognostic value.", "contents": "Studies on Crohn's disease. 1. The relationship between Yersinia enterocolitica infection and terminal ileitis. Patients with terminal ileitis or regional enterocolitis have been examined for signs of infection due to Yersinia enterocolitica serotype 3. The patients were grouped according to the length of preoperative history. Among 18 patients with preoperative symptoms of one week or less there were nine with positive signs of Yersinia enterocolitica infection. None of these patients developed the chronic form of Crohn's disease while two of the primarily Yersinia negative patients progressed to the chronic form. Among nine patients with preoperative symptoms of one week to three months there was one patient with positive signs of Yersinia enterocolitica infection. This patient has remained healthy whereas seven of the negative ones progressed to the chronic form of Crohn's disease. None of the patients with established Crohn's disease of the chronic form had signs of recent Yersinia infection. The findings indicate that patients with acute terminal ileitis and positive signs of Yersinia infection are not likely to progress to the chronic form of Crohn's disease. Bacteriologic and serologic investigation for Yersinia infection are therefore of prognostic value."} {"id": "PMID:1266548", "title": "Primary torsion of the whole greater omentum. A case report and review of the literature.", "content": "A case of primary torsion of the whole greater omentum is described. The patient was admitted to the hospital for severe abdominal pain. An emergency operation revealed that the whole greater omentum had twisted around its pedicle and was strangulated and gangrenous. The omentum was removed. The patient's recovery was uneventful. The literature is reviewed and discussed.", "contents": "Primary torsion of the whole greater omentum. A case report and review of the literature. A case of primary torsion of the whole greater omentum is described. The patient was admitted to the hospital for severe abdominal pain. An emergency operation revealed that the whole greater omentum had twisted around its pedicle and was strangulated and gangrenous. The omentum was removed. The patient's recovery was uneventful. The literature is reviewed and discussed."} {"id": "PMID:1266549", "title": "Optimal suction system for dissection work in surgery.", "content": "A new system for improved suction in surgical dissection work is presented, in which the suction tube end has slits. The air suction capacity of the pump is 30 litres a minute, and the maximal vacuum pressure in the systems is limited to -0.3 at by means of a membrane pressure regulator. This system allows a continuous atraumatic suction with adequate suction capacity and convenient operation.", "contents": "Optimal suction system for dissection work in surgery. A new system for improved suction in surgical dissection work is presented, in which the suction tube end has slits. The air suction capacity of the pump is 30 litres a minute, and the maximal vacuum pressure in the systems is limited to -0.3 at by means of a membrane pressure regulator. This system allows a continuous atraumatic suction with adequate suction capacity and convenient operation."} {"id": "PMID:1266554", "title": "Electroencephalographic study of children during ketamine anesthesia.", "content": "EEG was recorded on nine occasions of ketamine anesthesia in eight children. Two of the patients were neurologically normal and six were under investigation for various neurological disorders. The EEG during the catatonic phase of ketamine anesthesia is characterized by alternating high amplitude delta complexes and periods of fast activity. The two cases which in the routine EEG showed focal paroxysmal activity did not show any electroencephalographic aggravation or clinical seizure during ketamine influence. One case exhibiting a subcortical type of epileptiform activity showed a marked potentiation of this activity with ketamine. On routine neurological examination during the catatonic phase of ketamine anesthesia the pharyngeal reflex was generally weak and failed altogether in two cases and corneal reflexes were absent in three cases.", "contents": "Electroencephalographic study of children during ketamine anesthesia. EEG was recorded on nine occasions of ketamine anesthesia in eight children. Two of the patients were neurologically normal and six were under investigation for various neurological disorders. The EEG during the catatonic phase of ketamine anesthesia is characterized by alternating high amplitude delta complexes and periods of fast activity. The two cases which in the routine EEG showed focal paroxysmal activity did not show any electroencephalographic aggravation or clinical seizure during ketamine influence. One case exhibiting a subcortical type of epileptiform activity showed a marked potentiation of this activity with ketamine. On routine neurological examination during the catatonic phase of ketamine anesthesia the pharyngeal reflex was generally weak and failed altogether in two cases and corneal reflexes were absent in three cases."} {"id": "PMID:1266555", "title": "Halothane-induced liver damage: an analysis of the material reported to the Swedish Adverse Drug Reaction Committee, 1966-1973.", "content": "An analysis of 94 reports to the Swedish Adverse Drug Reaction Committee of patients with liver injury after surgery and halothane anaesthesia (including 13 fatal cases) has not been able to reveal any other factors responsible for the liver injury than the halothane administration. Eighty-two per cent of the total material and 12 out of 13 fatal cases had had multiple exposures. Our results suggest that the liver injury becomes more severe after repeated exposures; maximum serum bilirubin and SGOT values are higher after an increasing number of halothane exposures.", "contents": "Halothane-induced liver damage: an analysis of the material reported to the Swedish Adverse Drug Reaction Committee, 1966-1973. An analysis of 94 reports to the Swedish Adverse Drug Reaction Committee of patients with liver injury after surgery and halothane anaesthesia (including 13 fatal cases) has not been able to reveal any other factors responsible for the liver injury than the halothane administration. Eighty-two per cent of the total material and 12 out of 13 fatal cases had had multiple exposures. Our results suggest that the liver injury becomes more severe after repeated exposures; maximum serum bilirubin and SGOT values are higher after an increasing number of halothane exposures."} {"id": "PMID:1266556", "title": "Thoracic epidural analgesia-II: prolongation in the early postoperative period by continuous injection of 1.0% bupivacaine.", "content": "Sixteen patients were given thoracic epidural analgesia at the T5-T6 level with 2 ml of 1.0% bupivacaine solution plain for pain relief after upper abdominal surgery. In 13 cases the analgesia was prolonged by continuous injection of 1.0% bupivacaine for 24 or 48 h. Onset time and segmental spread of the analgesia are presented as well as segmental spread, intensity of the blockade, and peak expiratory flow rates during prolongation. Signs of tachyphylaxis were noticed, and also signs of accumulation of bupivacaine in plasma. A high incidence of urinary retention occurred. The method is not considered to be ideal for pain relief after upper abdominal surgery.", "contents": "Thoracic epidural analgesia-II: prolongation in the early postoperative period by continuous injection of 1.0% bupivacaine. Sixteen patients were given thoracic epidural analgesia at the T5-T6 level with 2 ml of 1.0% bupivacaine solution plain for pain relief after upper abdominal surgery. In 13 cases the analgesia was prolonged by continuous injection of 1.0% bupivacaine for 24 or 48 h. Onset time and segmental spread of the analgesia are presented as well as segmental spread, intensity of the blockade, and peak expiratory flow rates during prolongation. Signs of tachyphylaxis were noticed, and also signs of accumulation of bupivacaine in plasma. A high incidence of urinary retention occurred. The method is not considered to be ideal for pain relief after upper abdominal surgery."} {"id": "PMID:1266557", "title": "Brain energy metabolism during the process of dying and after cardiopulmonary resuscitation.", "content": "In order to study the problem of how fast and to what degree severe hypoxic brain tissue changes are reversed after reoxygenation, we challenged the viability of the brain by exposing experimental animals to anoxia of such a duration that cardiopulmonary resuscitation was just possible. The brain tissue concentrations of glucose, lactate, pyruvate and of ATP, ADP, AMP and phosphocreatine were determined. Two series of experiments were carried out. In the first, groups of rats deprived of oxygen for 1, 2, 4 and 6 min were studied in order to show brain tissue changes in the period of impending death as well as the changes coinciding with the onset of clinical death (blood pressure zero). In addition, one group maintained at a rectal temperature of 37 +/- 0.5 degrees C and ventilated for 60 min with an oxygen free gas mixture was included aimed at representing a state of irreversibility. In the second series, restitution after 6 min of no oxygen supply was studied 10 min, 1/2 h, 1 h, and 2 h after cardiopulmonary resuscitation. Attempts were also made to correlate biochemical changes to EEG status and to clinical recovery. The restitution study showed that oxidative phosphorylation of the brain tissue was rapidly resumed with normalization of the adenylate energy charge in all animals in which the pump function of the heart could be restored by our artificial means. However, there was a strikingly poor correlation between recovery of mitochondrial function and restitution of EEG or clinical recovery. Thus, it seems likely that a delayed functional restitution is not due to energy failure but to other biochemical changes or to biophysical alterations not revealed by the present type of study.", "contents": "Brain energy metabolism during the process of dying and after cardiopulmonary resuscitation. In order to study the problem of how fast and to what degree severe hypoxic brain tissue changes are reversed after reoxygenation, we challenged the viability of the brain by exposing experimental animals to anoxia of such a duration that cardiopulmonary resuscitation was just possible. The brain tissue concentrations of glucose, lactate, pyruvate and of ATP, ADP, AMP and phosphocreatine were determined. Two series of experiments were carried out. In the first, groups of rats deprived of oxygen for 1, 2, 4 and 6 min were studied in order to show brain tissue changes in the period of impending death as well as the changes coinciding with the onset of clinical death (blood pressure zero). In addition, one group maintained at a rectal temperature of 37 +/- 0.5 degrees C and ventilated for 60 min with an oxygen free gas mixture was included aimed at representing a state of irreversibility. In the second series, restitution after 6 min of no oxygen supply was studied 10 min, 1/2 h, 1 h, and 2 h after cardiopulmonary resuscitation. Attempts were also made to correlate biochemical changes to EEG status and to clinical recovery. The restitution study showed that oxidative phosphorylation of the brain tissue was rapidly resumed with normalization of the adenylate energy charge in all animals in which the pump function of the heart could be restored by our artificial means. However, there was a strikingly poor correlation between recovery of mitochondrial function and restitution of EEG or clinical recovery. Thus, it seems likely that a delayed functional restitution is not due to energy failure but to other biochemical changes or to biophysical alterations not revealed by the present type of study."} {"id": "PMID:1266558", "title": "The postanesthetic antiemetic effect of premedication with dehydrobenzperidol before ether anesthesia.", "content": "A study was performed to evaluate the antiemetic effects after ether anesthesia when dehydrobenzperidol (DHB) and pentobarbital were used for premedication and to compare these effects with halthane anesthesia when pentobarbital was used as premedication. Eighty-four patients undergoing minor surgical operations were randomly divided into three groups. The patients received ether and ether DHB 0.2 mg/kg or pentobarbital 2 mg/kg for premedication, or halothane and pentobarbital 2 mg/kg for premedication. The complaints of nausea and vomiting were recorded 24 h after anesthesia. We found that DHB compared to pentobarbital had a greater antiemetic effect after ether anesthesia, but the difference was not significant (P greater than 0.05). However, if only persistent nausea and vomiting were considered, the difference was significant (P less than 0.05). The incidence of nausea/vomiting after ether anesthesia with DHB as premedication was a little higher compared to halothane anesthesia with pentobarbital as premedication, but the difference was not significant (P greater than 0.05). However, if only persistent nausea/vomiting was considered, the incidence of complaints was equal in the two groups. It is concluded that when used for premedication to ether anesthesia DHB seems to lead to less postanesthetic nausea/vomiting than pentobarbital. Further DHB seems able to reduce the incidence of nausea/vomiting after ether anesthesia roughly to the level of that seen after pentobarbital premedication for halothane anesthesia.", "contents": "The postanesthetic antiemetic effect of premedication with dehydrobenzperidol before ether anesthesia. A study was performed to evaluate the antiemetic effects after ether anesthesia when dehydrobenzperidol (DHB) and pentobarbital were used for premedication and to compare these effects with halthane anesthesia when pentobarbital was used as premedication. Eighty-four patients undergoing minor surgical operations were randomly divided into three groups. The patients received ether and ether DHB 0.2 mg/kg or pentobarbital 2 mg/kg for premedication, or halothane and pentobarbital 2 mg/kg for premedication. The complaints of nausea and vomiting were recorded 24 h after anesthesia. We found that DHB compared to pentobarbital had a greater antiemetic effect after ether anesthesia, but the difference was not significant (P greater than 0.05). However, if only persistent nausea and vomiting were considered, the difference was significant (P less than 0.05). The incidence of nausea/vomiting after ether anesthesia with DHB as premedication was a little higher compared to halothane anesthesia with pentobarbital as premedication, but the difference was not significant (P greater than 0.05). However, if only persistent nausea/vomiting was considered, the incidence of complaints was equal in the two groups. It is concluded that when used for premedication to ether anesthesia DHB seems to lead to less postanesthetic nausea/vomiting than pentobarbital. Further DHB seems able to reduce the incidence of nausea/vomiting after ether anesthesia roughly to the level of that seen after pentobarbital premedication for halothane anesthesia."} {"id": "PMID:1266559", "title": "Evaluation of a new spirometer based on a fluidistor technique.", "content": "Using a mechanical model and human subjects a new spirometer based on fluidistor principles was evaluated. At normal minute volumes the fluidistor was accurate to within +/-5% when compared with a Bernstein spirometer. It underread at low volumes and overread at high. Prolonged expiratory time constant as well as the use of gas with low density increased the error. The instrument was somewhat sensitive to variation in breathing frequency and gas flow pattern but insensitive to moisture. The resistance to gas flow of the instrument itself was fairly high. The fluidistor is based on a sound and simple principle (no movable parts). It proved to be stable and easy to handle and accurate enough for clinical use in anaesthesia and intensive care. The tendency of the spirometer to underread at low flow and to overread at high flow could possibly be substantially reduced if the instrument was provided with several flow heads so that the oscillation volume could be individually adapted to the gas flow rate to be studied.", "contents": "Evaluation of a new spirometer based on a fluidistor technique. Using a mechanical model and human subjects a new spirometer based on fluidistor principles was evaluated. At normal minute volumes the fluidistor was accurate to within +/-5% when compared with a Bernstein spirometer. It underread at low volumes and overread at high. Prolonged expiratory time constant as well as the use of gas with low density increased the error. The instrument was somewhat sensitive to variation in breathing frequency and gas flow pattern but insensitive to moisture. The resistance to gas flow of the instrument itself was fairly high. The fluidistor is based on a sound and simple principle (no movable parts). It proved to be stable and easy to handle and accurate enough for clinical use in anaesthesia and intensive care. The tendency of the spirometer to underread at low flow and to overread at high flow could possibly be substantially reduced if the instrument was provided with several flow heads so that the oscillation volume could be individually adapted to the gas flow rate to be studied."} {"id": "PMID:1266560", "title": "Pindolol (Visc\u00e9n) in persistent ventricular fibrillation. A case report.", "content": "The beneficial effect of a beta-blocking agent (pindolol), given as an adjuvant to DC-shock and lidocaine therapy in a case of heart resuscitation is reported. A 65-year-old female patient was operated for an abdominal aortic aneurysm. At the conclusion of the operation, which was prolonged and difficult, the patient developed alternating ventricular tachycardia and fibrillation. Within a time interval of 50 min electrical defibrillation was performed 20 to 25 times, and as much as 1100 mg of lidocaine was administered. Simultaneously, combined internal/external cardiac massage was performed. The patient's arrhythmia continued to recur after defibrillation until pindolol in dosages of 0.2 mg had been given twice intravenously. A permanent sinus rhythm was then achieved.", "contents": "Pindolol (Visc\u00e9n) in persistent ventricular fibrillation. A case report. The beneficial effect of a beta-blocking agent (pindolol), given as an adjuvant to DC-shock and lidocaine therapy in a case of heart resuscitation is reported. A 65-year-old female patient was operated for an abdominal aortic aneurysm. At the conclusion of the operation, which was prolonged and difficult, the patient developed alternating ventricular tachycardia and fibrillation. Within a time interval of 50 min electrical defibrillation was performed 20 to 25 times, and as much as 1100 mg of lidocaine was administered. Simultaneously, combined internal/external cardiac massage was performed. The patient's arrhythmia continued to recur after defibrillation until pindolol in dosages of 0.2 mg had been given twice intravenously. A permanent sinus rhythm was then achieved."} {"id": "PMID:1266561", "title": "The effect of nitrous oxide on oxygen consumption and blood flow in the cerebral cortex of the rat.", "content": "The effect of 70% nitrous oxide upon cerebral oxygen consumption (CMRo2) and cerebral blood flow (CBF) was studied in artificially ventilated rats. The control groups consisted of unanaesthetized animals in which a stress-induced increase in CMRo2 and CBF was prevented by previous adrenalectomy, or by administration of a beta blocker (propranolol). There were no significant differences in CMRo2 between animals ventilated with either N2O or N2. It is concluded that if nitrous oxide depresses cerebral metabolism the depression cannot exceed 10%.", "contents": "The effect of nitrous oxide on oxygen consumption and blood flow in the cerebral cortex of the rat. The effect of 70% nitrous oxide upon cerebral oxygen consumption (CMRo2) and cerebral blood flow (CBF) was studied in artificially ventilated rats. The control groups consisted of unanaesthetized animals in which a stress-induced increase in CMRo2 and CBF was prevented by previous adrenalectomy, or by administration of a beta blocker (propranolol). There were no significant differences in CMRo2 between animals ventilated with either N2O or N2. It is concluded that if nitrous oxide depresses cerebral metabolism the depression cannot exceed 10%."} {"id": "PMID:1266562", "title": "Temporal lobe epilepsy. Etiological factors and surgical results.", "content": "Seventy-four patients with temporal lobe epilepsy, resistant to medication, who in 1960-1969 underwent unilateral temporal lobe resection at Rigshospitalet, Copenhagen. In only 12 patients was no etiological factor found. In three-quarters of the patients a peri- or postnatal injury was the suspected etiology of the epilepsy; and in one-third, a history of complications in the actual and/or abnormal outcome of a previous pregnancy was recorded. Only seven patients had experienced febrile convulsions. Patients with certain combinations of etiological factors, including encephalitis, have a poor prognosis regarding relief from seizures. Patients in whom an abnormal outcome of the mother's previous pregnancies is recorded have a poor prognosis as regards psychiatric normalization. Apart from this no correlation has been found between the surgical results and the numbers or types of the various etiological factors.", "contents": "Temporal lobe epilepsy. Etiological factors and surgical results. Seventy-four patients with temporal lobe epilepsy, resistant to medication, who in 1960-1969 underwent unilateral temporal lobe resection at Rigshospitalet, Copenhagen. In only 12 patients was no etiological factor found. In three-quarters of the patients a peri- or postnatal injury was the suspected etiology of the epilepsy; and in one-third, a history of complications in the actual and/or abnormal outcome of a previous pregnancy was recorded. Only seven patients had experienced febrile convulsions. Patients with certain combinations of etiological factors, including encephalitis, have a poor prognosis regarding relief from seizures. Patients in whom an abnormal outcome of the mother's previous pregnancies is recorded have a poor prognosis as regards psychiatric normalization. Apart from this no correlation has been found between the surgical results and the numbers or types of the various etiological factors."} {"id": "PMID:1266563", "title": "Pneumoencephalographic findings in various primary and secondary muscular disorders.", "content": "Pneumoencephalography was carried out in 23 patients with various muscular disorders, i.e. spinal neurogenic atrophy, classified as Wohlfart-Kugelberg-Welander's and Charcot-Marie-Tooth's diseases, and muscular dystrophy. EEG-registrations and psychological testing were carried out. Pneumoencephalography revealed ventricular enlargement and cortical changes in 17 out of 23 cases. Changes were found in all three groups studied; cortical changes were, however, only found in the neurogenic atrophy groups. Cases where there clearly might be exogenous causes for ventricular dilatation were excluded. The changes found, therefore, supposedly form an integral part of the disease process. It should be emphasized that the precaution does not entirely exclude a traumatic etiology in some cases. EEG-registrations (pathological in three out of 20 cases) as well as psychological evaluation (pathological in six out of 14 cases) supported the assumption of organic brain changes. Pneumoencephalography, however, seemed to be the most sensitive parameter for unveiling brain involvement in these disorders.", "contents": "Pneumoencephalographic findings in various primary and secondary muscular disorders. Pneumoencephalography was carried out in 23 patients with various muscular disorders, i.e. spinal neurogenic atrophy, classified as Wohlfart-Kugelberg-Welander's and Charcot-Marie-Tooth's diseases, and muscular dystrophy. EEG-registrations and psychological testing were carried out. Pneumoencephalography revealed ventricular enlargement and cortical changes in 17 out of 23 cases. Changes were found in all three groups studied; cortical changes were, however, only found in the neurogenic atrophy groups. Cases where there clearly might be exogenous causes for ventricular dilatation were excluded. The changes found, therefore, supposedly form an integral part of the disease process. It should be emphasized that the precaution does not entirely exclude a traumatic etiology in some cases. EEG-registrations (pathological in three out of 20 cases) as well as psychological evaluation (pathological in six out of 14 cases) supported the assumption of organic brain changes. Pneumoencephalography, however, seemed to be the most sensitive parameter for unveiling brain involvement in these disorders."} {"id": "PMID:1266564", "title": "Interferon in the serum and cerebrospinal fluid in patients with multiple sclerosis and other neurological disorders.", "content": "The presence of interferon (IF) was investigated in serum and cerebrospinal fluid (CSF) from neurological patients. Significant titres of IF were found both in the serum and in the CSF in about half of the patients suffering from acute encephalitis and from multiple sclerosis (MS), but not in patients suffering from various non-inflammatory disorders in the central nervous system (CNS) or in the peripheral nervous system (PNS), and not in the serum of healthy blood donors. Significant IF titres in the CSF were regularly associated with significant titres in the serum, but the converse was not true. Interferon levels were not correlated to cell counts in the CSF; nor to concentration of IgG and albumin in serum and CSF; nor to presence of electrophoretically oligoclonal IgG patterns; nor to hemagglutinating and gel-precipitation antibodies against measles. IF levels were lower in the serum of patients having reduced serum/CSF ratios for measles antibody than those with normal ratios. The data may indicate that MS is linked to factors which induce IF production in the CNS.", "contents": "Interferon in the serum and cerebrospinal fluid in patients with multiple sclerosis and other neurological disorders. The presence of interferon (IF) was investigated in serum and cerebrospinal fluid (CSF) from neurological patients. Significant titres of IF were found both in the serum and in the CSF in about half of the patients suffering from acute encephalitis and from multiple sclerosis (MS), but not in patients suffering from various non-inflammatory disorders in the central nervous system (CNS) or in the peripheral nervous system (PNS), and not in the serum of healthy blood donors. Significant IF titres in the CSF were regularly associated with significant titres in the serum, but the converse was not true. Interferon levels were not correlated to cell counts in the CSF; nor to concentration of IgG and albumin in serum and CSF; nor to presence of electrophoretically oligoclonal IgG patterns; nor to hemagglutinating and gel-precipitation antibodies against measles. IF levels were lower in the serum of patients having reduced serum/CSF ratios for measles antibody than those with normal ratios. The data may indicate that MS is linked to factors which induce IF production in the CNS."} {"id": "PMID:1266565", "title": "Epidemiology of Parkinson's disease in Finland.", "content": "This investigation was conducted to clarify the epidemiology of Parkinson's disease in Finland. A community survey was made in a selected area in southwest Finland in addition to an analysis of Finnish mortality statistics for Parkinson's disease. The annual mortality rate from Parkinson's disease was found to average 2 per 100,000 population. Almost 70 per cent of the deaths occurred between 65-79 years of age. The total and age-specific mortality rates for males were greater than those for females whereas the proportionate mortality rates were almost identical. This was considered to indicate that suggestions of greater male prevalence, based on mortality statistics, do not appear justified. On prevalence day, Dec. 31st, 1971, 484 patients with Parkinson's disease (of which 444 were personally examined) lived in the area of investigation (population 402,988), the prevalence rate being 120.1 per 100,000 population. The highest annual incidence rate was 16.6 per 100,000 population. The age-specific prevalence rates showed a rapid increase after the 50th year of age. The greatest prevalence was shown by the age group 70-79 years of age in which almost 0.8 per cent of the population are affected. Age-specific incidence rates also displayed an increase after the 50th year of age. The greatest incidence was observed in the age group 70-79 years of age in which almost 1 per 1,000 of the population are annually affected by the disease. A difference between the sexes was demonstrable in the prevalence and incidence rates showing greater values for females, but in the age-specific frequencies the differences were reduced. This probably reflects the difference between the age structures of the male and female populations, suggesting that both sexes have a similar risk of being affected by the disease. The permanent age structure shown by idiopathic patients in comparison with previous investigations as well as the increased mean age and proportionate decrease of postencephalitic patients was found to be in disagreement with the cohort theory according to which all parkinsonian patients are previously victims of encephalitis lethargica.", "contents": "Epidemiology of Parkinson's disease in Finland. This investigation was conducted to clarify the epidemiology of Parkinson's disease in Finland. A community survey was made in a selected area in southwest Finland in addition to an analysis of Finnish mortality statistics for Parkinson's disease. The annual mortality rate from Parkinson's disease was found to average 2 per 100,000 population. Almost 70 per cent of the deaths occurred between 65-79 years of age. The total and age-specific mortality rates for males were greater than those for females whereas the proportionate mortality rates were almost identical. This was considered to indicate that suggestions of greater male prevalence, based on mortality statistics, do not appear justified. On prevalence day, Dec. 31st, 1971, 484 patients with Parkinson's disease (of which 444 were personally examined) lived in the area of investigation (population 402,988), the prevalence rate being 120.1 per 100,000 population. The highest annual incidence rate was 16.6 per 100,000 population. The age-specific prevalence rates showed a rapid increase after the 50th year of age. The greatest prevalence was shown by the age group 70-79 years of age in which almost 0.8 per cent of the population are affected. Age-specific incidence rates also displayed an increase after the 50th year of age. The greatest incidence was observed in the age group 70-79 years of age in which almost 1 per 1,000 of the population are annually affected by the disease. A difference between the sexes was demonstrable in the prevalence and incidence rates showing greater values for females, but in the age-specific frequencies the differences were reduced. This probably reflects the difference between the age structures of the male and female populations, suggesting that both sexes have a similar risk of being affected by the disease. The permanent age structure shown by idiopathic patients in comparison with previous investigations as well as the increased mean age and proportionate decrease of postencephalitic patients was found to be in disagreement with the cohort theory according to which all parkinsonian patients are previously victims of encephalitis lethargica."} {"id": "PMID:1266566", "title": "Disturbances of micturition in Parkinson's disease.", "content": "During the years 1970-1974, a total of 44 patients referred by neurologists to the Urological Laboratory were classified in the following groups: paralysis agitans (27), postencephalitic parkinsonism (5), cerebral arteriosclerosis and parkinsonism (7) and cerebral arteriosclerosis and parkinsonism, suspected (5). Bladder function was assessed on the basis of cystometry and urodynamic investigation. A high frequency of supranuclear bladder paresis (SNP) was found, although unequally distributed in the different diagnostic groups. Stereotactic operations on the thalamic nuclei seemed to be correlated with SNP. The question was raised whether SNP was part of the parkinsonian syndrome or merely signs and symptoms related to ageing.", "contents": "Disturbances of micturition in Parkinson's disease. During the years 1970-1974, a total of 44 patients referred by neurologists to the Urological Laboratory were classified in the following groups: paralysis agitans (27), postencephalitic parkinsonism (5), cerebral arteriosclerosis and parkinsonism (7) and cerebral arteriosclerosis and parkinsonism, suspected (5). Bladder function was assessed on the basis of cystometry and urodynamic investigation. A high frequency of supranuclear bladder paresis (SNP) was found, although unequally distributed in the different diagnostic groups. Stereotactic operations on the thalamic nuclei seemed to be correlated with SNP. The question was raised whether SNP was part of the parkinsonian syndrome or merely signs and symptoms related to ageing."} {"id": "PMID:1266567", "title": "The electrocardiogram in young adults with ischaemic stroke.", "content": "Electrocardiograms in young adults with ischaemic stroke were analysed for abnormalities within 24 h after the onset of symptoms. Fifteen patients out of 44 had some ECG abnormality, mainly ST-T changes, sinus tachycardia and minor disturbances of intraventricular conductance. In most cases the ECG abnormality could be attributed to some extracerebral cause. It is concluded that ischaemic brain lesion per se never, or very rarely, affects the electrocardiogram.", "contents": "The electrocardiogram in young adults with ischaemic stroke. Electrocardiograms in young adults with ischaemic stroke were analysed for abnormalities within 24 h after the onset of symptoms. Fifteen patients out of 44 had some ECG abnormality, mainly ST-T changes, sinus tachycardia and minor disturbances of intraventricular conductance. In most cases the ECG abnormality could be attributed to some extracerebral cause. It is concluded that ischaemic brain lesion per se never, or very rarely, affects the electrocardiogram."} {"id": "PMID:1266568", "title": "Representation of cutaneous afferents by fluoride-resistant acid phosphatase (FRAP)-active terminals in the rat substantia gelatinosa rolandi.", "content": "While transection of the sciatic nerve results in a complete ipsilateral extinction of FRAP activity in respective segments of the rat spinal cord, cutaneous denervation of the hind leg induces a patchy disappearance of this same enzyme in the Rolando substance. The possible participation of FRAP in metabolism of the primary sensory transmitter substance, its relation to substance P and its involvement in gating mechanisms are discussed.", "contents": "Representation of cutaneous afferents by fluoride-resistant acid phosphatase (FRAP)-active terminals in the rat substantia gelatinosa rolandi. While transection of the sciatic nerve results in a complete ipsilateral extinction of FRAP activity in respective segments of the rat spinal cord, cutaneous denervation of the hind leg induces a patchy disappearance of this same enzyme in the Rolando substance. The possible participation of FRAP in metabolism of the primary sensory transmitter substance, its relation to substance P and its involvement in gating mechanisms are discussed."} {"id": "PMID:1266569", "title": "Biphasic response on oral glucose tolerance testing in myotonic dystrophy.", "content": "Oral glucose tolerance tests have been carried out on 40 patients with myotonic dystrophy, and 50 hospitalized control patients. A biphasic response was found in 19 myotonic dystrophy patients (49 per cent), compared with 12 of the control population (24 per cent). In 9 patients with myotonic dystrophy (23 per cent), the height of the second peak was greater than or equal to 20 mg/100 ml, the corresponding figure for the control group being 2 patients (4 per cent) (P less than 0.005).", "contents": "Biphasic response on oral glucose tolerance testing in myotonic dystrophy. Oral glucose tolerance tests have been carried out on 40 patients with myotonic dystrophy, and 50 hospitalized control patients. A biphasic response was found in 19 myotonic dystrophy patients (49 per cent), compared with 12 of the control population (24 per cent). In 9 patients with myotonic dystrophy (23 per cent), the height of the second peak was greater than or equal to 20 mg/100 ml, the corresponding figure for the control group being 2 patients (4 per cent) (P less than 0.005)."} {"id": "PMID:1266570", "title": "Basal metabolic rate in patients with hydrocephalus. On the cause of lowered basal metabolic rate in myotonic dystrophy.", "content": "Myotonic dystrophy seems to have a hypometabolism of non-thyroid origin. The hypometabolism could hypothetically be caused by : 1) reduction in muscle mass, 2) hydrocephalus ex vacuo, an integral part of the disorder, or 3) the basic disease process itself. Possibility 2) was explored by determining basal metabolic rate (BMR) in 41 patients with dilatation. A BMR of less than -10 per cent was found in eight cases. The ventricles were categorized in three groups according to width. No decrease in mean BMR was found in cases with a marked ventricular enlargement. Thus, ventricular dilatation per se does not seem to lead to hypometabolism.", "contents": "Basal metabolic rate in patients with hydrocephalus. On the cause of lowered basal metabolic rate in myotonic dystrophy. Myotonic dystrophy seems to have a hypometabolism of non-thyroid origin. The hypometabolism could hypothetically be caused by : 1) reduction in muscle mass, 2) hydrocephalus ex vacuo, an integral part of the disorder, or 3) the basic disease process itself. Possibility 2) was explored by determining basal metabolic rate (BMR) in 41 patients with dilatation. A BMR of less than -10 per cent was found in eight cases. The ventricles were categorized in three groups according to width. No decrease in mean BMR was found in cases with a marked ventricular enlargement. Thus, ventricular dilatation per se does not seem to lead to hypometabolism."} {"id": "PMID:1266571", "title": "Quantitative development of choroid plexuses in chick embryo cerebral ventricles.", "content": "Quantitative development of choroid plexuses in cerebral ventricles of chick embryos was investigated by means of the planary projection of the choroid plexuses from the time the plexuses reached a consistent flattened structure. Choroid plexuses in the lateral cerbral ventricles were studied from day 6, the plexus in the third cerebral ventricle from day 8, and the plexus in the fourth cerebral ventricle from day 11 of incubation. Regardless of the microscopic origin of these choroid plexuses, their development reached a growth maximum on day 15 of incubation, after which there was a slight regression. The regression was gradual in the plexus of the third cerebral ventricle but a transient enlargement of plexuses in the laternal and in the fourth cerebral ventricle was observed between days 18 and 19. The enlargement of choroid plexuses in the lateral cerebral ventricles was caused by a flattening of the villi, whereas that of the plexus in the fourth cerebral ventricle was caused by thinning and yawning of the villi. The area of choroid plexuses in the lateral cerebral ventricles was six or seven times larger than the sum of the areas of the remaining choroid plexuses.", "contents": "Quantitative development of choroid plexuses in chick embryo cerebral ventricles. Quantitative development of choroid plexuses in cerebral ventricles of chick embryos was investigated by means of the planary projection of the choroid plexuses from the time the plexuses reached a consistent flattened structure. Choroid plexuses in the lateral cerbral ventricles were studied from day 6, the plexus in the third cerebral ventricle from day 8, and the plexus in the fourth cerebral ventricle from day 11 of incubation. Regardless of the microscopic origin of these choroid plexuses, their development reached a growth maximum on day 15 of incubation, after which there was a slight regression. The regression was gradual in the plexus of the third cerebral ventricle but a transient enlargement of plexuses in the laternal and in the fourth cerebral ventricle was observed between days 18 and 19. The enlargement of choroid plexuses in the lateral cerebral ventricles was caused by a flattening of the villi, whereas that of the plexus in the fourth cerebral ventricle was caused by thinning and yawning of the villi. The area of choroid plexuses in the lateral cerebral ventricles was six or seven times larger than the sum of the areas of the remaining choroid plexuses."} {"id": "PMID:1266572", "title": "Effect of hydrocortisone on the growth of choroid plexus and composition of cerebrospinal fluid in the developing chick embryo.", "content": "The effect of hydrocortisone on the telencephalic choroid plexus and on the osmolarity and ionic compositon of CSF was studied 48 hours after its administration onto the chorio-allantoic membrane of chick embryos on days 11 and 13 (20 mug per egg) or on day 17 (40 mug per egg). Hydrocortisone significantly reduced the choroid plexus area on days 13 and 15 but was ineffective on day 19. The topical analysis of these choroid plexuses, influenced by the steroid, pointed to a decrease of the growth activity in those parts whose proliferation was intensive. The transient population of villi in the apical part of these plexuses was the most sensitive. Those parts, being morphogenetically inactive or whose morphogenetic changes were not caused by the cellular proliferstion, were not affected significantly. The osmolarity of CSF increased significantly during the investigated period simultaneously with an increase in the sodium and chloride concentration while the concentrations of potassium did not change significantly. Hydrocortisone evoked a precocious increase in the osmolarity of CSF on days 13 and 15. Contemporarily, the potassium concentration in CSF was elevated while the steroid failed to change the sodium and chloride concentrations.", "contents": "Effect of hydrocortisone on the growth of choroid plexus and composition of cerebrospinal fluid in the developing chick embryo. The effect of hydrocortisone on the telencephalic choroid plexus and on the osmolarity and ionic compositon of CSF was studied 48 hours after its administration onto the chorio-allantoic membrane of chick embryos on days 11 and 13 (20 mug per egg) or on day 17 (40 mug per egg). Hydrocortisone significantly reduced the choroid plexus area on days 13 and 15 but was ineffective on day 19. The topical analysis of these choroid plexuses, influenced by the steroid, pointed to a decrease of the growth activity in those parts whose proliferation was intensive. The transient population of villi in the apical part of these plexuses was the most sensitive. Those parts, being morphogenetically inactive or whose morphogenetic changes were not caused by the cellular proliferstion, were not affected significantly. The osmolarity of CSF increased significantly during the investigated period simultaneously with an increase in the sodium and chloride concentration while the concentrations of potassium did not change significantly. Hydrocortisone evoked a precocious increase in the osmolarity of CSF on days 13 and 15. Contemporarily, the potassium concentration in CSF was elevated while the steroid failed to change the sodium and chloride concentrations."} {"id": "PMID:1266573", "title": "Homocarnosinosis. 2. A familial metabolic disorder associated with spastic paraplegia, progressive mental deficiency, and retinal pigmentation.", "content": "Homocarnosine, the brain-specific dipeptide of gamma-aminobutyric acid (GABA) and histidine, was found to be elevated in the CSF, i.e. approximately 20 times the mean control level, in two brothers and one sister. All three were similarly afflicted, i.e. with a progressive spastic paraplegia, progressive mental deterioration and retinal pigmentation. A sister was healthy, and there was no other occurrence of similar symptoms in the family. The clinical symptoms in the affected individuals seem to differ from those in other reported families. The unaffected sister, the father and two maternal aunts exhibited a normal CSF homocarnosine level, whereas the mother, who showed no definite clinical symptoms, showed a markedly elevated CSF homocarnosine level. The explanation for the latter finding remains obscure.", "contents": "Homocarnosinosis. 2. A familial metabolic disorder associated with spastic paraplegia, progressive mental deficiency, and retinal pigmentation. Homocarnosine, the brain-specific dipeptide of gamma-aminobutyric acid (GABA) and histidine, was found to be elevated in the CSF, i.e. approximately 20 times the mean control level, in two brothers and one sister. All three were similarly afflicted, i.e. with a progressive spastic paraplegia, progressive mental deterioration and retinal pigmentation. A sister was healthy, and there was no other occurrence of similar symptoms in the family. The clinical symptoms in the affected individuals seem to differ from those in other reported families. The unaffected sister, the father and two maternal aunts exhibited a normal CSF homocarnosine level, whereas the mother, who showed no definite clinical symptoms, showed a markedly elevated CSF homocarnosine level. The explanation for the latter finding remains obscure."} {"id": "PMID:1266574", "title": "A comparison between agar gel electrophoresis and CSF serum quotients of IgG and albumin in neurological disease.", "content": "CSF and serum was obtained from 216 patients with neurological or psychoneurotic symptoms and the concentrations of albumin and IgG were immunologically determined. The IgG/albumin index, calculated as the quotient of the CSF/serum ratios of IgG and albumin was compared with electrophoresis on agar gel. In \"normal\" cases, the IgG/albumin index was between 0.26-0.66. Pathological electrophoresis, i.e. with two or more IgG bands in the gamma globulin region was found in 85 per cent of the MS patients; in 29 per cent of the patients with a possible demyelinating disease; in 41 per cent of patients with CNS infection; and in 4 per cent of patients with other neurological disorders; whereas an increased IgG/albumin index ( greater than 0.66) was found in 88 per cent of the MS patients; in 43 per cent of the patients with a possible demyelinating disease; in 50 per cent of the patients with CNS infection; in 11 per cent of patients with immunological disorders; and in 18 per cent of patients with other neurological diseases. The increase of the IgG/albumin index was sometimes moderate (0.67-0.90), except in patients with MS, syphilis and other CNS infections, where a pathological electrophoresis combined with an IgG/albumin index above 1.0 was found to be a valuable support for the clinical diagnosis.", "contents": "A comparison between agar gel electrophoresis and CSF serum quotients of IgG and albumin in neurological disease. CSF and serum was obtained from 216 patients with neurological or psychoneurotic symptoms and the concentrations of albumin and IgG were immunologically determined. The IgG/albumin index, calculated as the quotient of the CSF/serum ratios of IgG and albumin was compared with electrophoresis on agar gel. In \"normal\" cases, the IgG/albumin index was between 0.26-0.66. Pathological electrophoresis, i.e. with two or more IgG bands in the gamma globulin region was found in 85 per cent of the MS patients; in 29 per cent of the patients with a possible demyelinating disease; in 41 per cent of patients with CNS infection; and in 4 per cent of patients with other neurological disorders; whereas an increased IgG/albumin index ( greater than 0.66) was found in 88 per cent of the MS patients; in 43 per cent of the patients with a possible demyelinating disease; in 50 per cent of the patients with CNS infection; in 11 per cent of patients with immunological disorders; and in 18 per cent of patients with other neurological diseases. The increase of the IgG/albumin index was sometimes moderate (0.67-0.90), except in patients with MS, syphilis and other CNS infections, where a pathological electrophoresis combined with an IgG/albumin index above 1.0 was found to be a valuable support for the clinical diagnosis."} {"id": "PMID:1266575", "title": "Multiple sclerosis and Hodgkin's disease in Denmark.", "content": "There has been a hypothesis that Hodgkin's disease in young adults and multiple sclerosis may have related causes because the age of clinical onset and the geographic distribution of both are similar. This hypothesis was tested for data in Denmark. Detweeen 1943-62, the average annual incidence rate for Hoadgkin's disease in Denmark was 2.25 per 100,000 population (2.68 male and 1.83 female). Between 1951-69, the average annual death rate for Hodgkin's disease was 2.15 per 100,000 (2.66 male and 1.64 female). The average annual incidence rate for multiple sclerosis in Denmark was calculated from age at onset for 2,481 prevalent cases of 1949, the 1940 population, and an average annual incidence of 128.86 cases for 1939-45: the average annual incidence rate per 100,000 was then 3.35 (3.00 male and 3.69 female). Age specific incidence and death rate for Hodgkin's disease in Denmark each showed a bimodal curve, with one peak at age 25-29 and the other at age 70-74; this was found for each sex, with male rates consistently higher than female. The age specific incidence rates for multiple sclerosis were clearly unimodal with a peak at age 25-29 more definite in females than males. Rates for MS were notably higher for young females than males but about equal by sex for those over the age of 30. The geographic distribution of multiple sclerosis within the counties (amter) of Denmark was markedly non-random, with the major concentration of high prevalence areas middle Jutland and on to Fyn. Geographic distribution of Hodgkin's disease, whether for the young or the old, and whether from incident or death cases, showed no significant variation from a homogeneous distribution. In formal testing there was no correlation of any Hodgkin's distribution with that of MS. A review of the Hodgkin's data for distribution in the United States, on which the original hypothesis was based, suggests the variation there may be little more than reporting artifact. Accordingly, we conclude that there is no relation between distributions of these two disorders, and the factors they do appear to have in common are either quite non-specific or of questionable validity. Thus there is no reason to believe that multiple sclerosis and Hodgkin's disease, even in the young, share a common etiology.", "contents": "Multiple sclerosis and Hodgkin's disease in Denmark. There has been a hypothesis that Hodgkin's disease in young adults and multiple sclerosis may have related causes because the age of clinical onset and the geographic distribution of both are similar. This hypothesis was tested for data in Denmark. Detweeen 1943-62, the average annual incidence rate for Hoadgkin's disease in Denmark was 2.25 per 100,000 population (2.68 male and 1.83 female). Between 1951-69, the average annual death rate for Hodgkin's disease was 2.15 per 100,000 (2.66 male and 1.64 female). The average annual incidence rate for multiple sclerosis in Denmark was calculated from age at onset for 2,481 prevalent cases of 1949, the 1940 population, and an average annual incidence of 128.86 cases for 1939-45: the average annual incidence rate per 100,000 was then 3.35 (3.00 male and 3.69 female). Age specific incidence and death rate for Hodgkin's disease in Denmark each showed a bimodal curve, with one peak at age 25-29 and the other at age 70-74; this was found for each sex, with male rates consistently higher than female. The age specific incidence rates for multiple sclerosis were clearly unimodal with a peak at age 25-29 more definite in females than males. Rates for MS were notably higher for young females than males but about equal by sex for those over the age of 30. The geographic distribution of multiple sclerosis within the counties (amter) of Denmark was markedly non-random, with the major concentration of high prevalence areas middle Jutland and on to Fyn. Geographic distribution of Hodgkin's disease, whether for the young or the old, and whether from incident or death cases, showed no significant variation from a homogeneous distribution. In formal testing there was no correlation of any Hodgkin's distribution with that of MS. A review of the Hodgkin's data for distribution in the United States, on which the original hypothesis was based, suggests the variation there may be little more than reporting artifact. Accordingly, we conclude that there is no relation between distributions of these two disorders, and the factors they do appear to have in common are either quite non-specific or of questionable validity. Thus there is no reason to believe that multiple sclerosis and Hodgkin's disease, even in the young, share a common etiology."} {"id": "PMID:1266576", "title": "Parkinson's disease treated with Sinemet or Madopar. A controlled multicenter trial.", "content": "92 patients with Parkinson's disease not previously treated with levodopa were considered as eligible for this triple-blind trial. Patients were allocated at random to treatment with either levodopa + benserazide ratio 4:1 (Madopar) or levodopa + carbidopa ratio 10:1 (Sinemet) using dosage schedules recommended by the manufacturers which they had to adhere to for 6 months. Unless prohibitive side-effects occurred daily maximum dosage of 800 mg levodopa + 200 mg benserazide respectively 1,500 mg levodopa + 150 mg carbidopa were obtained after 6 weeks and 3 weeks, respectively. The effect of the two schedules on the Parkinsonian symptoms were equal and appeared equally fast. The frequency of gastrointestinal side-effects and involuntary movements were significantly higher and more severe for Sinemet than for Madopar. These side effects are usually symptoms of levodopa overdosing, but whether or not a different dosage schedule with Sinemet would have given fewer side-effects without concurrent lower efficacy remains open to speculation. The treatment schedules did not differ with regard to other side-effects and influence on blood pressure. Neither treatment seemed to influence liver function, renal function and hematological parameters in a statistically way.", "contents": "Parkinson's disease treated with Sinemet or Madopar. A controlled multicenter trial. 92 patients with Parkinson's disease not previously treated with levodopa were considered as eligible for this triple-blind trial. Patients were allocated at random to treatment with either levodopa + benserazide ratio 4:1 (Madopar) or levodopa + carbidopa ratio 10:1 (Sinemet) using dosage schedules recommended by the manufacturers which they had to adhere to for 6 months. Unless prohibitive side-effects occurred daily maximum dosage of 800 mg levodopa + 200 mg benserazide respectively 1,500 mg levodopa + 150 mg carbidopa were obtained after 6 weeks and 3 weeks, respectively. The effect of the two schedules on the Parkinsonian symptoms were equal and appeared equally fast. The frequency of gastrointestinal side-effects and involuntary movements were significantly higher and more severe for Sinemet than for Madopar. These side effects are usually symptoms of levodopa overdosing, but whether or not a different dosage schedule with Sinemet would have given fewer side-effects without concurrent lower efficacy remains open to speculation. The treatment schedules did not differ with regard to other side-effects and influence on blood pressure. Neither treatment seemed to influence liver function, renal function and hematological parameters in a statistically way."} {"id": "PMID:1266577", "title": "Clonus depression by propranolol.", "content": "Propranolol administered i.v. to spastic patients was found to be capable of depressing clonus. The drug exerts its action on the spinal cord but does not influence dynamic spindle activity or alpha-motoneurone activity as tested by the T (Achilles tendon) and H reflexes. It may disinhibit the tonic stretch reflex. Thus, clonus is dependent not only on dynamic spindle activity but also on another, probably inhibitory, mechanism.", "contents": "Clonus depression by propranolol. Propranolol administered i.v. to spastic patients was found to be capable of depressing clonus. The drug exerts its action on the spinal cord but does not influence dynamic spindle activity or alpha-motoneurone activity as tested by the T (Achilles tendon) and H reflexes. It may disinhibit the tonic stretch reflex. Thus, clonus is dependent not only on dynamic spindle activity but also on another, probably inhibitory, mechanism."} {"id": "PMID:1266578", "title": "Damage of skeletal muscle in rats by immunoglobulins. I. Pathophysiological data and lightmicroscopic observations.", "content": "An experimental model of the autoimmune process was developed to study the pathophysiological and structural changes in immunomyopathies. Immune-sera derived from three muscle proteins--myofibril, myosin and actin--produced immunomyopathies for study. The pathophysiological data show that the general muscle efficiency began to decrease with the early stages of treatment and reflected a severe disorder to muscle function with the progression of time. Parallel changes were also observed by light microscopy.", "contents": "Damage of skeletal muscle in rats by immunoglobulins. I. Pathophysiological data and lightmicroscopic observations. An experimental model of the autoimmune process was developed to study the pathophysiological and structural changes in immunomyopathies. Immune-sera derived from three muscle proteins--myofibril, myosin and actin--produced immunomyopathies for study. The pathophysiological data show that the general muscle efficiency began to decrease with the early stages of treatment and reflected a severe disorder to muscle function with the progression of time. Parallel changes were also observed by light microscopy."} {"id": "PMID:1266579", "title": "Damage of skeletal muscle in rats by immunoglobulins. II. Ultrastructural studies.", "content": "An experimental model of the autoimmune process was developed to study the ultrastructural aspects of immunomyopathies. Every type of muscle fibre organelle was affected and the severity of injury increased in direct proportion to time following immunization. It is suggested that ultrastructural methods are useful in studies concerned with the analysis of structural aspects of experimental immunomyopathies.", "contents": "Damage of skeletal muscle in rats by immunoglobulins. II. Ultrastructural studies. An experimental model of the autoimmune process was developed to study the ultrastructural aspects of immunomyopathies. Every type of muscle fibre organelle was affected and the severity of injury increased in direct proportion to time following immunization. It is suggested that ultrastructural methods are useful in studies concerned with the analysis of structural aspects of experimental immunomyopathies."} {"id": "PMID:1266580", "title": "Chronic tonsillar herniation: an attempt at classifying chronic hernitations at the foramen magnum.", "content": "A system is presented for the classification of chronic herniations of the cerebellar tonsils in the absence of space-occupying intracranial lesions, based on a survey of the literature and 13 own cases. The Arnold-Chiari malformation in adults typically involves herniation of the cerebellar tonsils instead of herniation of the vermis as is typical when it occurs in infancy. Identification of chronic tonsillar herniation with the Arnold-Chiari malformation in adults was thought to require at least one other sign of the Arnold-Chiari complex, e.g. a medullary deformity. Cases for which chronic herniation and sclerosis of the cerebellar tonsils present as the only nervous lesion are classified as \"chronic tonsillar herniation\". Such cases may manifest with neurological symptoms during adult life, or they may be found incidentally at autopsy. Attention is drawn to the occurrence of chronic tonsillar herniation in 7 infants and children where it apparently represents a cause of sudden unexpected death. The overlap between chronic tonsillar herniation and the Arnold-Chiari malformation of adults is discussed in regard to the frequence of associated osseous anomalies, hydrocephalus and syringomyelia.", "contents": "Chronic tonsillar herniation: an attempt at classifying chronic hernitations at the foramen magnum. A system is presented for the classification of chronic herniations of the cerebellar tonsils in the absence of space-occupying intracranial lesions, based on a survey of the literature and 13 own cases. The Arnold-Chiari malformation in adults typically involves herniation of the cerebellar tonsils instead of herniation of the vermis as is typical when it occurs in infancy. Identification of chronic tonsillar herniation with the Arnold-Chiari malformation in adults was thought to require at least one other sign of the Arnold-Chiari complex, e.g. a medullary deformity. Cases for which chronic herniation and sclerosis of the cerebellar tonsils present as the only nervous lesion are classified as \"chronic tonsillar herniation\". Such cases may manifest with neurological symptoms during adult life, or they may be found incidentally at autopsy. Attention is drawn to the occurrence of chronic tonsillar herniation in 7 infants and children where it apparently represents a cause of sudden unexpected death. The overlap between chronic tonsillar herniation and the Arnold-Chiari malformation of adults is discussed in regard to the frequence of associated osseous anomalies, hydrocephalus and syringomyelia."} {"id": "PMID:1266581", "title": "Influence of ouabain on the fine structure of teleost retina.", "content": "In this study the effect of intraocular injection of 10 mul 10(-5) M ouabain on the retinal fine structure of the cyprinide teleost Carassius carassius is described. The final concentration of the drug in the eye-bulb was approximately 3-10(-6)M. After 8--24 h the ouabain application produces alterations in the retinal ganglion cells, that progress subsequently to necrobiosis. The outer horizontal cells of the inner nuclear layer show a severe cytoplasmic swelling that is reversible and disappears 8 days after ouabain injection. Amacrines, bipolars and receptor cells are relatively insensitive to the ouabain-induced Na+-K+-ATPase-inhibition. The differential susceptibility to ouabain in the retina possibly reflects a cell-specific pattern of Na+-K+-ATPase-activity or -concentration, whose physiological significance is discussed.", "contents": "Influence of ouabain on the fine structure of teleost retina. In this study the effect of intraocular injection of 10 mul 10(-5) M ouabain on the retinal fine structure of the cyprinide teleost Carassius carassius is described. The final concentration of the drug in the eye-bulb was approximately 3-10(-6)M. After 8--24 h the ouabain application produces alterations in the retinal ganglion cells, that progress subsequently to necrobiosis. The outer horizontal cells of the inner nuclear layer show a severe cytoplasmic swelling that is reversible and disappears 8 days after ouabain injection. Amacrines, bipolars and receptor cells are relatively insensitive to the ouabain-induced Na+-K+-ATPase-inhibition. The differential susceptibility to ouabain in the retina possibly reflects a cell-specific pattern of Na+-K+-ATPase-activity or -concentration, whose physiological significance is discussed."} {"id": "PMID:1266582", "title": "Sudanophilic leucodystrophy: report of a case with tigroid demyelination of the centrum ovale.", "content": "A 17-year-old girl with negative familial and personal history developed a progressive neurologic disorder characterized by cortical amaurosis, metal deterioration and spastic tetraparesis. Death occurred one year after the onset of symptoms. Histopathologic examination of the C.N.S. showed the presence of extensive, discontinuous demyelination of the white matter of the centrum ovale, with preservation of perivascular myelin islets, associated with massive fat degradation, loss of axons and severe astroglial proliferation. This case belongs to the group of sudanophilic leucodystrophies, being an atypical case, a transition between pure sudanophilic leucodystrophy and the group of Pelizaeus-Merzbacher's disease.", "contents": "Sudanophilic leucodystrophy: report of a case with tigroid demyelination of the centrum ovale. A 17-year-old girl with negative familial and personal history developed a progressive neurologic disorder characterized by cortical amaurosis, metal deterioration and spastic tetraparesis. Death occurred one year after the onset of symptoms. Histopathologic examination of the C.N.S. showed the presence of extensive, discontinuous demyelination of the white matter of the centrum ovale, with preservation of perivascular myelin islets, associated with massive fat degradation, loss of axons and severe astroglial proliferation. This case belongs to the group of sudanophilic leucodystrophies, being an atypical case, a transition between pure sudanophilic leucodystrophy and the group of Pelizaeus-Merzbacher's disease."} {"id": "PMID:1266583", "title": "Postoperative restoration of muscle strength after intramedullary nailing of fractures of the femoral shaft.", "content": "The maximal isometric muscle strength of hip abduction, knee extension and knee flexion was measured in 23 patients operated on for femur diaphyseal fractures and fitted with a stable intramedullary K\u00fcntscher nail after reaming of the medullary cavity. The trauma, the immobilization and the surgery influenced the musculature of the operated as well as the intact leg. The muscle power recovered in a couple of years, but even after 2-6 years a significantly reduced power was found in the knee extensors, and a probably significant reduction in the power of the knee flexors in the operated leg when the two legs were compared. Malrotation of the fracture seemed to adversely affect the recovery of muscle power.", "contents": "Postoperative restoration of muscle strength after intramedullary nailing of fractures of the femoral shaft. The maximal isometric muscle strength of hip abduction, knee extension and knee flexion was measured in 23 patients operated on for femur diaphyseal fractures and fitted with a stable intramedullary K\u00fcntscher nail after reaming of the medullary cavity. The trauma, the immobilization and the surgery influenced the musculature of the operated as well as the intact leg. The muscle power recovered in a couple of years, but even after 2-6 years a significantly reduced power was found in the knee extensors, and a probably significant reduction in the power of the knee flexors in the operated leg when the two legs were compared. Malrotation of the fracture seemed to adversely affect the recovery of muscle power."} {"id": "PMID:1266584", "title": "Mechanical properties of dried defatted spongy bone.", "content": "A study has been made of the compressive strength, compression at rupture, limit of proportionality, compression at the limit of proportionality and the modulus of elasticity of spongy bone from vertebrae and tibias. The specimens were obtained from autopsy subjects of both sexes aged 14 to 89 years. There was a qualitative deterioration of most of the strength parameters with age, and also differences between the sexes and between vertebrae and tibia. Spongy bone was found to have the unusual mechanical property that, despite rupture, its compressive strength often steadily increased; this was especially the case for vertebrae from young males.", "contents": "Mechanical properties of dried defatted spongy bone. A study has been made of the compressive strength, compression at rupture, limit of proportionality, compression at the limit of proportionality and the modulus of elasticity of spongy bone from vertebrae and tibias. The specimens were obtained from autopsy subjects of both sexes aged 14 to 89 years. There was a qualitative deterioration of most of the strength parameters with age, and also differences between the sexes and between vertebrae and tibia. Spongy bone was found to have the unusual mechanical property that, despite rupture, its compressive strength often steadily increased; this was especially the case for vertebrae from young males."} {"id": "PMID:1266585", "title": "Tibial torsion in untreated congenital clubfoot.", "content": "Current methods of measurement were reassessed by the study of tibial torsion in 1000 normal legs using the tropometer, the caliper and X-rays. No significant difference in the reproducibility of results was found and the simpler clinical methods appeared to be satisfactory for practical purposes. The spontaneous evolution of leg torsion in clubfoot was studied in forty-two neglected and previously untreated cases, who were seen for the first time after they had begun walking. Comparison with the torsion observed in the legs of healthy children of a corresponding age proved that untreated clubfoot is not associated with pathological torsion. The place of rotation osteotomy in the treatment of clubfoot is discussed.", "contents": "Tibial torsion in untreated congenital clubfoot. Current methods of measurement were reassessed by the study of tibial torsion in 1000 normal legs using the tropometer, the caliper and X-rays. No significant difference in the reproducibility of results was found and the simpler clinical methods appeared to be satisfactory for practical purposes. The spontaneous evolution of leg torsion in clubfoot was studied in forty-two neglected and previously untreated cases, who were seen for the first time after they had begun walking. Comparison with the torsion observed in the legs of healthy children of a corresponding age proved that untreated clubfoot is not associated with pathological torsion. The place of rotation osteotomy in the treatment of clubfoot is discussed."} {"id": "PMID:1266586", "title": "The incidence of Achilles tendon rupture.", "content": "During the years 1950-1973, 229 cases of Achilles tendon rupture were diagnosed in the city of Malm\u00f6. More than half of the injuries were caused by sporting activities, the most common being badminton and football (soccer). Ruptures caused by injuries other than sports injuries were found in considerably older subjects. During the period investigated the incidence of Achilles tendon rupture increased in the city more than could be accounted for by changes in the population. This increase could only be partly explained by the increasing interest in sporting activities in the population at risk.", "contents": "The incidence of Achilles tendon rupture. During the years 1950-1973, 229 cases of Achilles tendon rupture were diagnosed in the city of Malm\u00f6. More than half of the injuries were caused by sporting activities, the most common being badminton and football (soccer). Ruptures caused by injuries other than sports injuries were found in considerably older subjects. During the period investigated the incidence of Achilles tendon rupture increased in the city more than could be accounted for by changes in the population. This increase could only be partly explained by the increasing interest in sporting activities in the population at risk."} {"id": "PMID:1266587", "title": "A comparison of plantar flexion torque with and without the triceps surae.", "content": "Torque generated about the ankle joints during maximum isometric contraction of the plantar flexor muscles was measured on a subject 4 months after unilateral excision of the entire triceps surae. Resulting torque output on the operated limb was 327 kg-cm, or 38 per cent of the 871 kg-cm total for the sound limb.", "contents": "A comparison of plantar flexion torque with and without the triceps surae. Torque generated about the ankle joints during maximum isometric contraction of the plantar flexor muscles was measured on a subject 4 months after unilateral excision of the entire triceps surae. Resulting torque output on the operated limb was 327 kg-cm, or 38 per cent of the 871 kg-cm total for the sound limb."} {"id": "PMID:1266588", "title": "Physical properties of fluorosis bone.", "content": "The bones of two patients, one with a moderate and one with a severe chronic industrial fluorosis (stage I-II and stage III), and the bones of three control persons were examined. The following parameters were determined: the fracture load, the fracture load/unit area (resistance to pressure) of the body of the first lumbar vertebra, the bending strength of the neck of the femur and of the lower third of the femur, the fracture load/unit area and the modulus of elasticity of femoral slices 2 cm thick and of precisely defined cylinders from the femoral cortex. The microhardness according to Vickers on the cross section of the femur was also determined. The results obtained are discussed with regard to fluoride therapy of osteoporosis.", "contents": "Physical properties of fluorosis bone. The bones of two patients, one with a moderate and one with a severe chronic industrial fluorosis (stage I-II and stage III), and the bones of three control persons were examined. The following parameters were determined: the fracture load, the fracture load/unit area (resistance to pressure) of the body of the first lumbar vertebra, the bending strength of the neck of the femur and of the lower third of the femur, the fracture load/unit area and the modulus of elasticity of femoral slices 2 cm thick and of precisely defined cylinders from the femoral cortex. The microhardness according to Vickers on the cross section of the femur was also determined. The results obtained are discussed with regard to fluoride therapy of osteoporosis."} {"id": "PMID:1266589", "title": "Postoperative wound infection after implant and removal of osteosynthetic material.", "content": "Osteosynthetic material was implanted and removal in 972 consecutive operations in the upper and lower extremity. Early post-operative wound infection developed significantly more often after osteosynthesis than after removal of the implant; neither sex nor age influenced significantly the frequency of wound infection. The latter was higher when insertion or removal of material was performed in the lower extremity than in the upper extremity. The hip and ankle regions were involved most often. Staph. aureus and Staph. albus predominated among the Gram-positive infections; gram-negative infections, however, occurred remarkably frequently, E. coli being the most common organism isolated. To decimate exogenous and endogenous contamination of the wounds during operation, aseptic and antiseptic measures should be reinforced. In operation in a region proven to carry a higher post-operative infectious risk, i.e. the hip and ankle, it is suggested that antibiotics should be administered at the time of osteosynthesis.", "contents": "Postoperative wound infection after implant and removal of osteosynthetic material. Osteosynthetic material was implanted and removal in 972 consecutive operations in the upper and lower extremity. Early post-operative wound infection developed significantly more often after osteosynthesis than after removal of the implant; neither sex nor age influenced significantly the frequency of wound infection. The latter was higher when insertion or removal of material was performed in the lower extremity than in the upper extremity. The hip and ankle regions were involved most often. Staph. aureus and Staph. albus predominated among the Gram-positive infections; gram-negative infections, however, occurred remarkably frequently, E. coli being the most common organism isolated. To decimate exogenous and endogenous contamination of the wounds during operation, aseptic and antiseptic measures should be reinforced. In operation in a region proven to carry a higher post-operative infectious risk, i.e. the hip and ankle, it is suggested that antibiotics should be administered at the time of osteosynthesis."} {"id": "PMID:1266590", "title": "Tissue reaction to methyl methacrylate monomer. A comparative study in the rabbit's ear on the toxicity of methyl methacrylate monomer of varying composition.", "content": "The aim of the present investigation was to evaluate if a bone cement monomer with a high concentration of accelerator (N,N-dimethyl-p-toluidine) is more toxic than a methyl methacrylate monomer, free from accelerator. 1) No difference in the acute local toxicity between CMW, Simplex-P and pure methyl methacrylate monomer was seen. 2) By gas chromatography. N,N-dimethyl-p-toluidine was shown to be water soluble to a small extent. Any bone cement monomer in current use can be fully dissolved in saline to a concentration of about 1 per cent.", "contents": "Tissue reaction to methyl methacrylate monomer. A comparative study in the rabbit's ear on the toxicity of methyl methacrylate monomer of varying composition. The aim of the present investigation was to evaluate if a bone cement monomer with a high concentration of accelerator (N,N-dimethyl-p-toluidine) is more toxic than a methyl methacrylate monomer, free from accelerator. 1) No difference in the acute local toxicity between CMW, Simplex-P and pure methyl methacrylate monomer was seen. 2) By gas chromatography. N,N-dimethyl-p-toluidine was shown to be water soluble to a small extent. Any bone cement monomer in current use can be fully dissolved in saline to a concentration of about 1 per cent."} {"id": "PMID:1266591", "title": "Free graft of fascial tube in flexor tendon repair in the digital sheath of the hand. An attempt at a composite tissue autograft.", "content": "Various reconstructive methods have been reported for cicatricial tendon beds. Since 1970, when the flexor tendon gliding mechanism of the finger has been damaged in the area of \"no man's land\" and conditions are less than optimal for conventional tendon grafting, the authors have attempted to graft a fascial tube including tendon and paratenon of the palmaris longus. The technique is described and the results reported.", "contents": "Free graft of fascial tube in flexor tendon repair in the digital sheath of the hand. An attempt at a composite tissue autograft. Various reconstructive methods have been reported for cicatricial tendon beds. Since 1970, when the flexor tendon gliding mechanism of the finger has been damaged in the area of \"no man's land\" and conditions are less than optimal for conventional tendon grafting, the authors have attempted to graft a fascial tube including tendon and paratenon of the palmaris longus. The technique is described and the results reported."} {"id": "PMID:1266592", "title": "Chordoma in Finland.", "content": "During the period 1953-1971, 20 cases of chordoma were reported to the Finnish Cancer Registry. Twelve of the patients were males. The mean annual (crude) incidence of chordoma in Finland was 0.30/10(6) in males, and 0.18/10(6) in females. Fifteen of the tumours were sacral, three vertebral, and two cranial. Local recurrences were common, and distant metastases were observed in 60 per cent of the cases; this exceeds the proportion usually mentioned in the literature. The commonest treatment was surgery combined with postoperative high-dose irradiation. The relative 5-year survival rate was 35 per cent, and the 10-year rate 18 per cent.", "contents": "Chordoma in Finland. During the period 1953-1971, 20 cases of chordoma were reported to the Finnish Cancer Registry. Twelve of the patients were males. The mean annual (crude) incidence of chordoma in Finland was 0.30/10(6) in males, and 0.18/10(6) in females. Fifteen of the tumours were sacral, three vertebral, and two cranial. Local recurrences were common, and distant metastases were observed in 60 per cent of the cases; this exceeds the proportion usually mentioned in the literature. The commonest treatment was surgery combined with postoperative high-dose irradiation. The relative 5-year survival rate was 35 per cent, and the 10-year rate 18 per cent."} {"id": "PMID:1266593", "title": "Multiple non-contiguous injuries to the spine.", "content": "Over a period of 4 years, 120 patients with an identified neurologic defect secondary to spinal cord injury were admitted to the UCD-Sacramento Medical Center. Of these cases five (4.2 per cent) were found to have multiple non-contiguous injuries to the spine which would have been capable of producing complete neurologic loss at either level. Proper treatment is dependent on diagnosis, and correct diagnosis is dependent on the awareness that multiple non-contiguous injuries to the vertebral column can occur in victims of severe motor vehicle accidents.", "contents": "Multiple non-contiguous injuries to the spine. Over a period of 4 years, 120 patients with an identified neurologic defect secondary to spinal cord injury were admitted to the UCD-Sacramento Medical Center. Of these cases five (4.2 per cent) were found to have multiple non-contiguous injuries to the spine which would have been capable of producing complete neurologic loss at either level. Proper treatment is dependent on diagnosis, and correct diagnosis is dependent on the awareness that multiple non-contiguous injuries to the vertebral column can occur in victims of severe motor vehicle accidents."} {"id": "PMID:1266594", "title": "Cervical spondylolisthesis.", "content": "A case is reported of cervical spondylolisthesis in a 12-year-old girl. The cervical spondylolisthesis has not progressed in the 2 years of observation.", "contents": "Cervical spondylolisthesis. A case is reported of cervical spondylolisthesis in a 12-year-old girl. The cervical spondylolisthesis has not progressed in the 2 years of observation."} {"id": "PMID:1266596", "title": "The Moore vitallium femoral-head prosthesis in fractures of the femoral neck.", "content": "A follow-up is given of early and late results in 109 arthroplasties with the self-locking Austin T. Moore vitallium femoral head prosthesis in fractures of the femoral neck on 106 patients. Operative indication was usually fresh medical fracture of the femoral neck in an elderly woman, or its late complication. The surgery was performed in a unit for general surgery also engaged in pre- and postgraduate teaching activities. Many operations were performed by residents engaged in general surgery or orthopaedics. Point scores according to a modification of Merle D'Aubign\u00e9's classification showed excellent or at least good results in 81 per cent of the 69 mobile patients. Because of deteriorated general physical condition 11 patients were chronically bed-ridden. Five patients could not be reached. In three instances the prosthesis was removed. 21 patients died, three during the stay in hospital and 18 later for reasons not connected with the operative procedure. The mortality during 40 months of observation corresponded fairly well to that expected in the age group for the population as a whole.", "contents": "The Moore vitallium femoral-head prosthesis in fractures of the femoral neck. A follow-up is given of early and late results in 109 arthroplasties with the self-locking Austin T. Moore vitallium femoral head prosthesis in fractures of the femoral neck on 106 patients. Operative indication was usually fresh medical fracture of the femoral neck in an elderly woman, or its late complication. The surgery was performed in a unit for general surgery also engaged in pre- and postgraduate teaching activities. Many operations were performed by residents engaged in general surgery or orthopaedics. Point scores according to a modification of Merle D'Aubign\u00e9's classification showed excellent or at least good results in 81 per cent of the 69 mobile patients. Because of deteriorated general physical condition 11 patients were chronically bed-ridden. Five patients could not be reached. In three instances the prosthesis was removed. 21 patients died, three during the stay in hospital and 18 later for reasons not connected with the operative procedure. The mortality during 40 months of observation corresponded fairly well to that expected in the age group for the population as a whole."} {"id": "PMID:1266597", "title": "Intertrochanteric osteotomy in the treatment of Perthes' disease.", "content": "Intertrochanteric osteotomy has been carried out in 34 children with Perthes' disease. Five weeks after the operation the patients were allowed to move about freely. The average postoperative follow-up period was 27 months. At that time the results seemed to be at least as good as those of Thomas' splint therapy. The varus-derotation osteotomy performed in the initial stage accelerated the process of reossification and seemed to prevent subluxation. According to our findings it is worthwhile correcting the subluxation even in cases with irreversible changes.", "contents": "Intertrochanteric osteotomy in the treatment of Perthes' disease. Intertrochanteric osteotomy has been carried out in 34 children with Perthes' disease. Five weeks after the operation the patients were allowed to move about freely. The average postoperative follow-up period was 27 months. At that time the results seemed to be at least as good as those of Thomas' splint therapy. The varus-derotation osteotomy performed in the initial stage accelerated the process of reossification and seemed to prevent subluxation. According to our findings it is worthwhile correcting the subluxation even in cases with irreversible changes."} {"id": "PMID:1266598", "title": "The effect of intertrochanteric osteotomy on the venous drainage of the femoral neck in Perthes' disease.", "content": "Intraosseous femoral neck venography was performed both pre- and postoperatively on 30 patients with Perthes' disease. At the time of the operation (osteotomy) and the preoperative venographies, the disease was in the initial stage in 16 patients, in the fragmentation stage in eight patients and in the restitution stage in six patients. As shown previously the venous drainage of the femoral neck preoperatively, in the initial and fragmentation stages of the disease, was different from the venous pattern of the healthy (control) hips in every case, indicating an obstruction of the venous flow. 4-15 months after the osteotomies this venous obstruction had disappeared completely or almost completely in most cases. This normalization happened sooner than expected on the basis of our findings with conservatively-treated patients.", "contents": "The effect of intertrochanteric osteotomy on the venous drainage of the femoral neck in Perthes' disease. Intraosseous femoral neck venography was performed both pre- and postoperatively on 30 patients with Perthes' disease. At the time of the operation (osteotomy) and the preoperative venographies, the disease was in the initial stage in 16 patients, in the fragmentation stage in eight patients and in the restitution stage in six patients. As shown previously the venous drainage of the femoral neck preoperatively, in the initial and fragmentation stages of the disease, was different from the venous pattern of the healthy (control) hips in every case, indicating an obstruction of the venous flow. 4-15 months after the osteotomies this venous obstruction had disappeared completely or almost completely in most cases. This normalization happened sooner than expected on the basis of our findings with conservatively-treated patients."} {"id": "PMID:1266599", "title": "Intraosseous pressure in the femoral head and greater trochanter before and 1-3 years after osteotomy for osteoarthritis of the hip joint.", "content": "To elucidate the long-term effect of osteotomy upon the intraosseous pressure in osteoarthritis of the hip, pressure measurements in the femoral head and greater trochanter were performed in 22 patients before intertrochanteric osteotomy and 11.5-33.5 months later, on the occasion of removing the osteosynthesis material after the osteotomy had healed. Preoperatively the mean pressure in the femoral head was higher (35.0 mmHg) than in the greater trochanter (23.4 mmHg). At follow-up the mean pressure in the femoral head had fallen, but not significantly (0.10 less than P less than 0.20). A significant reduction in pressure (0.001 less than P less than 0.005) was found in 10 patients in whom the primary pressure was high (exceeding 35 mmHg) and in 16 patients seen at follow-up less than two years after the osteotomy (0.01 less than P less than 0.02), whereas with a longer observation period there was a tendency towards an increasing pressure. The trochanteric pressures accompanied the pressures in the femoral head, but without significant changes. No close correlation was found between intraosseous pressure and pain at rest. The operation had a good clinical effect, especially upon the pain at rest. A reduction in intraosseous hypertension may be a contributory cause, but the tendency to another increase in pressure after a long observation period indicates the possibility of a subsequent recurrence.", "contents": "Intraosseous pressure in the femoral head and greater trochanter before and 1-3 years after osteotomy for osteoarthritis of the hip joint. To elucidate the long-term effect of osteotomy upon the intraosseous pressure in osteoarthritis of the hip, pressure measurements in the femoral head and greater trochanter were performed in 22 patients before intertrochanteric osteotomy and 11.5-33.5 months later, on the occasion of removing the osteosynthesis material after the osteotomy had healed. Preoperatively the mean pressure in the femoral head was higher (35.0 mmHg) than in the greater trochanter (23.4 mmHg). At follow-up the mean pressure in the femoral head had fallen, but not significantly (0.10 less than P less than 0.20). A significant reduction in pressure (0.001 less than P less than 0.005) was found in 10 patients in whom the primary pressure was high (exceeding 35 mmHg) and in 16 patients seen at follow-up less than two years after the osteotomy (0.01 less than P less than 0.02), whereas with a longer observation period there was a tendency towards an increasing pressure. The trochanteric pressures accompanied the pressures in the femoral head, but without significant changes. No close correlation was found between intraosseous pressure and pain at rest. The operation had a good clinical effect, especially upon the pain at rest. A reduction in intraosseous hypertension may be a contributory cause, but the tendency to another increase in pressure after a long observation period indicates the possibility of a subsequent recurrence."} {"id": "PMID:1266600", "title": "Studies on the anatomy of the facial nerve.", "content": "The present study on the anatomy of the human facial nerve is based on the results of a series of gross dissections, and histological and electro-diagnostic examinations. From our findings it follows that there is a definite spatial orientation of the peripheral branches in the facial nerve trunk. The results of the morphologic studies are in agreement with those obtained by electric stimulation combined with electromyography.", "contents": "Studies on the anatomy of the facial nerve. The present study on the anatomy of the human facial nerve is based on the results of a series of gross dissections, and histological and electro-diagnostic examinations. From our findings it follows that there is a definite spatial orientation of the peripheral branches in the facial nerve trunk. The results of the morphologic studies are in agreement with those obtained by electric stimulation combined with electromyography."} {"id": "PMID:1266601", "title": "[Reactions of mucous membrane in middle ear].", "content": "Antibiotic therapy has transformed classic picture of otitis media, especially as a result of changed immunological conditions. Histopathology of the mucous membrane has shown badly inflamed and healing areas close together. Cellular proliferation, as in granulomas and adhesion formation, has now become more important than purulent complications. The middle ear drainage, normally provided by good function of the eustachian tube and a drum perforation have now become a focus of interest. A blocked tube and an intact eardrum cause not only serous otitis media but, when untreated, otitis media chronica adhesiva as well. We have studied these problems histologically, histochemically and cytologically.", "contents": "[Reactions of mucous membrane in middle ear]. Antibiotic therapy has transformed classic picture of otitis media, especially as a result of changed immunological conditions. Histopathology of the mucous membrane has shown badly inflamed and healing areas close together. Cellular proliferation, as in granulomas and adhesion formation, has now become more important than purulent complications. The middle ear drainage, normally provided by good function of the eustachian tube and a drum perforation have now become a focus of interest. A blocked tube and an intact eardrum cause not only serous otitis media but, when untreated, otitis media chronica adhesiva as well. We have studied these problems histologically, histochemically and cytologically."} {"id": "PMID:1266602", "title": "Histopathological alterations of the mucosal folds in chronic otitis media.", "content": "The autogenesis and evolution of the mucosal folds were studied. They play an important part in the immunological defense system of the middle ear. The anatomy and topography of these mucosal duplications together with their pathophysiological effects explain the clinical development in the various forms of middle ear infection and disturbances of the aeration of the middle ear in case of an open and well functioning Eustachian tube.", "contents": "Histopathological alterations of the mucosal folds in chronic otitis media. The autogenesis and evolution of the mucosal folds were studied. They play an important part in the immunological defense system of the middle ear. The anatomy and topography of these mucosal duplications together with their pathophysiological effects explain the clinical development in the various forms of middle ear infection and disturbances of the aeration of the middle ear in case of an open and well functioning Eustachian tube."} {"id": "PMID:1266603", "title": "Secretory otitis media. Comparison of nasal and aural cytology.", "content": "Aural and nasal cytology is compared in a series of 105 patients with secretory otitis media (SOM). In aural smears the cellular picture consisted mainly of lymphocytes, leukocytes and phagocytes but eosinophils and basophilic cells were absent. In the nose, the most frequent cells were leukocytes, while lymphocytes were seldom seen in greater numbers. Increased numbers of eosinophils were found in 20% of the patients. IgE values in the serum of 69 patients and in 8 aural effusions were mostly within normal limits and SOM could not be considered to be a result of circulating IgE-dependent reaction. Cytotoxic leukocyte test with food allergens to test this etiologic factor in SOM is at present in progress.", "contents": "Secretory otitis media. Comparison of nasal and aural cytology. Aural and nasal cytology is compared in a series of 105 patients with secretory otitis media (SOM). In aural smears the cellular picture consisted mainly of lymphocytes, leukocytes and phagocytes but eosinophils and basophilic cells were absent. In the nose, the most frequent cells were leukocytes, while lymphocytes were seldom seen in greater numbers. Increased numbers of eosinophils were found in 20% of the patients. IgE values in the serum of 69 patients and in 8 aural effusions were mostly within normal limits and SOM could not be considered to be a result of circulating IgE-dependent reaction. Cytotoxic leukocyte test with food allergens to test this etiologic factor in SOM is at present in progress."} {"id": "PMID:1266604", "title": "Ultrastructural study of taste buds at rest and after stimulation, and comparative study between type III cell and Merkel cells.", "content": "Changes in the pore region of the cell membrane have been studied in order to learn if this region plays an active part in the preneural phase of taste. We have observed, though not consistently, that the pore size is variable and that their contents are not constantly amorphous or homogeneous. The results are not so significant, however, as to allow of the formulation of any firm conclusions. The similarity between type III cells and Merkel cells (cells of the tactile system) was surprising. The probable role of the type III cell in taste is discussed.", "contents": "Ultrastructural study of taste buds at rest and after stimulation, and comparative study between type III cell and Merkel cells. Changes in the pore region of the cell membrane have been studied in order to learn if this region plays an active part in the preneural phase of taste. We have observed, though not consistently, that the pore size is variable and that their contents are not constantly amorphous or homogeneous. The results are not so significant, however, as to allow of the formulation of any firm conclusions. The similarity between type III cells and Merkel cells (cells of the tactile system) was surprising. The probable role of the type III cell in taste is discussed."} {"id": "PMID:1266605", "title": "Scanning electron microscopic studies of the staples in normal and in some pathological and experimental conditions.", "content": "By means of the electro-scanning microscope we were able to demonstrate the three-dimensional bony structure of the normal stapes, and the variations in structure of the different stages of otosclerosis. One case of osteopsatyrosis is also discussed. The callus formation in an experimentally fractured footplate is compared with otosclerosis.", "contents": "Scanning electron microscopic studies of the staples in normal and in some pathological and experimental conditions. By means of the electro-scanning microscope we were able to demonstrate the three-dimensional bony structure of the normal stapes, and the variations in structure of the different stages of otosclerosis. One case of osteopsatyrosis is also discussed. The callus formation in an experimentally fractured footplate is compared with otosclerosis."} {"id": "PMID:1266606", "title": "Regeneration in the VIII nerve.", "content": "After transection of the VIII nerve in the inner meatus, 95% of the cochlear neurons and practically all efferent fibres degenerate and disappear. In long-term survivals, different phenomena indicate the regeneration properties of many, probably efferent or vestibular nerve fibres. The few remaining afferent neurons react to the lesion of their central axon with enormous proliferations of their peripheral branches in the organ of Corti.", "contents": "Regeneration in the VIII nerve. After transection of the VIII nerve in the inner meatus, 95% of the cochlear neurons and practically all efferent fibres degenerate and disappear. In long-term survivals, different phenomena indicate the regeneration properties of many, probably efferent or vestibular nerve fibres. The few remaining afferent neurons react to the lesion of their central axon with enormous proliferations of their peripheral branches in the organ of Corti."} {"id": "PMID:1266607", "title": "Postural behaviour and motion sickness.", "content": "One of the acting techniques used in Kyogen, a classical Japanese stage comedy, prompted two questions: why is it that one may suffer from motion sickness as a car passenger, but, as a driver, escape its effects? And how can one learn postural adjustment against motion sickness by repeatedly travelling in vehicles?", "contents": "Postural behaviour and motion sickness. One of the acting techniques used in Kyogen, a classical Japanese stage comedy, prompted two questions: why is it that one may suffer from motion sickness as a car passenger, but, as a driver, escape its effects? And how can one learn postural adjustment against motion sickness by repeatedly travelling in vehicles?"} {"id": "PMID:1266608", "title": "Technical variations in clinical ostial patency tests.", "content": "The usefulness of nasopharyngeal-antral pressure difference recording as a part of clinical ostial patency testing is demonstrated by statistical calculations from 507 patency tests. This method offers a quick confirmation of the comparison of pressure variation measured by anterior rhinomanometry and by antral pressure recordings which are the main elements of a consecutive patency test. In addition, the nasopharyngeal-antral recording has many of the advantages of a simultaneous patency test. When this difference recording is applied, the nasal reference pressure recording can also be omitted without any loss of information sought by the patency test.", "contents": "Technical variations in clinical ostial patency tests. The usefulness of nasopharyngeal-antral pressure difference recording as a part of clinical ostial patency testing is demonstrated by statistical calculations from 507 patency tests. This method offers a quick confirmation of the comparison of pressure variation measured by anterior rhinomanometry and by antral pressure recordings which are the main elements of a consecutive patency test. In addition, the nasopharyngeal-antral recording has many of the advantages of a simultaneous patency test. When this difference recording is applied, the nasal reference pressure recording can also be omitted without any loss of information sought by the patency test."} {"id": "PMID:1266610", "title": "Social handicap among workers with noise-induced hearing loss.", "content": "A thorough examination of hearing and hearing loss among workers in the saw- and papermill industries in northern Sweden showed that even a serious hearing loss does not give the expected social handicap.", "contents": "Social handicap among workers with noise-induced hearing loss. A thorough examination of hearing and hearing loss among workers in the saw- and papermill industries in northern Sweden showed that even a serious hearing loss does not give the expected social handicap."} {"id": "PMID:1266609", "title": "Further contribution in the densitometric study of the labyrinthic capsule with special reference to the bottom of the internal auditory meatus.", "content": "The quantity of minerals in the labyrinthic capsule of the basal coil and of the separating wall facing the internal auditory meatus in different life periods was determined by the densitometric method. The quantity of minerals is reduced in the labyrinthic capsule and in the separating wall in spite of the bone apposition and increasing thickness of the separating wall.", "contents": "Further contribution in the densitometric study of the labyrinthic capsule with special reference to the bottom of the internal auditory meatus. The quantity of minerals in the labyrinthic capsule of the basal coil and of the separating wall facing the internal auditory meatus in different life periods was determined by the densitometric method. The quantity of minerals is reduced in the labyrinthic capsule and in the separating wall in spite of the bone apposition and increasing thickness of the separating wall."} {"id": "PMID:1266611", "title": "Postauricular (12 msec latency) responses to acoustic stimuli in patients with peripheral, facial nerve palsy.", "content": "The postauricular (12 msec latency) response to a loud click stimulation was investigated in 23 patients with facial nerve palsy. Of these patients 21 had an intracranial cause for the facial palsy and 2 had an extracranial cause. Only in those with the extracranial facial nerve damage could the response be obtained from both sides. When the nerve was damaged intracranially there was no response on the paralysed side. This seems to indicate that the posterior auricular muscle is the effector of the presumed sonomotor reflex arc involving the cochlea, cochlear nerve and nuclei, undetermined brainstem pathway, facial motor nucleus, facial nerve and the muscles supplied by it.", "contents": "Postauricular (12 msec latency) responses to acoustic stimuli in patients with peripheral, facial nerve palsy. The postauricular (12 msec latency) response to a loud click stimulation was investigated in 23 patients with facial nerve palsy. Of these patients 21 had an intracranial cause for the facial palsy and 2 had an extracranial cause. Only in those with the extracranial facial nerve damage could the response be obtained from both sides. When the nerve was damaged intracranially there was no response on the paralysed side. This seems to indicate that the posterior auricular muscle is the effector of the presumed sonomotor reflex arc involving the cochlea, cochlear nerve and nuclei, undetermined brainstem pathway, facial motor nucleus, facial nerve and the muscles supplied by it."} {"id": "PMID:1266612", "title": "Effects of acoustic trauma on corti's ganglion.", "content": "The ultrastructural features of Corti's ganglion cells were studied in guinea pigs subjected to a wide-band plain 100 dB SPL white noise (12 hr/day for 30 days). Regression was primarily observed in cells belonging to the 2nd turn and took the form of detachment of the membrane from the myelin sheath, and cytoplasmic retraction to the point of destruction of the entire cell. Intensely osmiophilic myelin bodies were frequent in Schwann cells, and in gangliar cells and their sheath. Multivesicular bodies were also common. A description of the regression noted in the myelin fibres is given. Attention is drawn to the fact that regression was not observed in sheathless fibres and cells; the latter formed about 5% of the ganglion population.", "contents": "Effects of acoustic trauma on corti's ganglion. The ultrastructural features of Corti's ganglion cells were studied in guinea pigs subjected to a wide-band plain 100 dB SPL white noise (12 hr/day for 30 days). Regression was primarily observed in cells belonging to the 2nd turn and took the form of detachment of the membrane from the myelin sheath, and cytoplasmic retraction to the point of destruction of the entire cell. Intensely osmiophilic myelin bodies were frequent in Schwann cells, and in gangliar cells and their sheath. Multivesicular bodies were also common. A description of the regression noted in the myelin fibres is given. Attention is drawn to the fact that regression was not observed in sheathless fibres and cells; the latter formed about 5% of the ganglion population."} {"id": "PMID:1266613", "title": "Measurement of oxygen tension in human perilymph.", "content": "The oxygen tension of the human perilymph has been determined without complications by using a technique based upon the polarographic principle. Carbon dioxide produced the most marked increase in oxygen tension in the human perilymph. No change in the perilymphatic PO2 was observed after administration of eupaverine and low molecular weight dextran. 5% CO2-95%O2 has been found to be the gas mixture producing the largest increase in oxygen tension in the human perilymph, without side effects. In order to achieve maximal oxygenation of the perilymph, the therapeutic administration of 5% CO2-95% O2 should continue for at least 30 minutes. At this preliminary stage it is not possible to assess the accuracy of the presented technique in determining the presence of a vascular disorder of the inner ear in patients.", "contents": "Measurement of oxygen tension in human perilymph. The oxygen tension of the human perilymph has been determined without complications by using a technique based upon the polarographic principle. Carbon dioxide produced the most marked increase in oxygen tension in the human perilymph. No change in the perilymphatic PO2 was observed after administration of eupaverine and low molecular weight dextran. 5% CO2-95%O2 has been found to be the gas mixture producing the largest increase in oxygen tension in the human perilymph, without side effects. In order to achieve maximal oxygenation of the perilymph, the therapeutic administration of 5% CO2-95% O2 should continue for at least 30 minutes. At this preliminary stage it is not possible to assess the accuracy of the presented technique in determining the presence of a vascular disorder of the inner ear in patients."} {"id": "PMID:1266614", "title": "Clinical application of auditory nerve responses recorded from the ear canal.", "content": "The practicality of recording auditory nerve responses in the routine practice of an otologist is demonstrated. Such recordings are particularly useful when the course of treatment requires a distinction between central or peripheral disorders. They are also helpful when it is difficult to obtain a valid audiogram. The electrical recordings from the auditory nerve can, in combination with standard audiological, otological and neurological examinations, present a more accurate picture of the patient's condition.", "contents": "Clinical application of auditory nerve responses recorded from the ear canal. The practicality of recording auditory nerve responses in the routine practice of an otologist is demonstrated. Such recordings are particularly useful when the course of treatment requires a distinction between central or peripheral disorders. They are also helpful when it is difficult to obtain a valid audiogram. The electrical recordings from the auditory nerve can, in combination with standard audiological, otological and neurological examinations, present a more accurate picture of the patient's condition."} {"id": "PMID:1266616", "title": "Uptake and release of alcohol by homograft tissues in tympanoplasty.", "content": "Alcohol is known to produce severe cochlear damage and it is possible that deafness as a complication of tympanoplasty can be caused by alcohol which remains in homograft materials after inadequate washing. An investigation was made in which the quantity of alcohol taken up by ossicles, cartilage, temporalis fascia, dura and ear-drum was estimated. The rate of release of alcohol from such materials into saline during washing was also measured. The amount absorbed was found to depend upon the nature of the material, its weight and its surface area. The rate of release of alcohol from these materials differed significantly for each material.", "contents": "Uptake and release of alcohol by homograft tissues in tympanoplasty. Alcohol is known to produce severe cochlear damage and it is possible that deafness as a complication of tympanoplasty can be caused by alcohol which remains in homograft materials after inadequate washing. An investigation was made in which the quantity of alcohol taken up by ossicles, cartilage, temporalis fascia, dura and ear-drum was estimated. The rate of release of alcohol from such materials into saline during washing was also measured. The amount absorbed was found to depend upon the nature of the material, its weight and its surface area. The rate of release of alcohol from these materials differed significantly for each material."} {"id": "PMID:1266615", "title": "Sound localization with phase audiometry.", "content": "A 500 Hz pure tone is presented binaurally with earphones. The tone is adjusted to give a midline impression at confortable loudness level. An electronic variable time delay line unit and a generator for randomizing the shift of the phase lag of the signal to the right or to the left ear, respectively, are used. By shortening the time delay the threshold of the recognition of the phase difference is reached. At every test sequence the tone is first presented in the center of the head without delay and then with delay. The patient runs the test by indicating in which ear the tone is heard. The phase difference is thus gradually reduced from 500 musec down to a threshold value of about 48 musec equal on right and left ears in normal-hearing subjects. The results of phase audiometry on subjects with normal hearing and with different types of hearing losses are in good agreement with the results of sound localization tests in free field. Phase audiometry seems to be of especial value in diagnosing retrocochlear lesions.", "contents": "Sound localization with phase audiometry. A 500 Hz pure tone is presented binaurally with earphones. The tone is adjusted to give a midline impression at confortable loudness level. An electronic variable time delay line unit and a generator for randomizing the shift of the phase lag of the signal to the right or to the left ear, respectively, are used. By shortening the time delay the threshold of the recognition of the phase difference is reached. At every test sequence the tone is first presented in the center of the head without delay and then with delay. The patient runs the test by indicating in which ear the tone is heard. The phase difference is thus gradually reduced from 500 musec down to a threshold value of about 48 musec equal on right and left ears in normal-hearing subjects. The results of phase audiometry on subjects with normal hearing and with different types of hearing losses are in good agreement with the results of sound localization tests in free field. Phase audiometry seems to be of especial value in diagnosing retrocochlear lesions."} {"id": "PMID:1266617", "title": "Ultrastructural investigations on the degenerative and regenerative processes in chorda tympani in bell's paralysis.", "content": "Our ultrastructural findings in investigated cases of Bell's palsy have demonstrated that the degenerative changes did not proceed at the same speed from the onset of the paralysis--in other words the regeneration changed in accordance with the topography of the nerve. Although the endoneural sheath preserved its integrity, swellings in the Schwann cells have attracted much attention. Furthermore the perineural tissue presented changes which were closely correlated with the degenerative and regenerative processes due to paralysis. In addition to these findings, although the interval between the onset of paralysis and the operation was the same in all our cases, the observation of a more severe degenerative picture of the nerves in the female patients may seem to be an interesting finding, but to the lack of an adequate number of cases which would enable a statistical evaluation, we are strongly, of the opinion that this subject deserves further study.", "contents": "Ultrastructural investigations on the degenerative and regenerative processes in chorda tympani in bell's paralysis. Our ultrastructural findings in investigated cases of Bell's palsy have demonstrated that the degenerative changes did not proceed at the same speed from the onset of the paralysis--in other words the regeneration changed in accordance with the topography of the nerve. Although the endoneural sheath preserved its integrity, swellings in the Schwann cells have attracted much attention. Furthermore the perineural tissue presented changes which were closely correlated with the degenerative and regenerative processes due to paralysis. In addition to these findings, although the interval between the onset of paralysis and the operation was the same in all our cases, the observation of a more severe degenerative picture of the nerves in the female patients may seem to be an interesting finding, but to the lack of an adequate number of cases which would enable a statistical evaluation, we are strongly, of the opinion that this subject deserves further study."} {"id": "PMID:1266622", "title": "The effect of steroids on differentiation and function of cultured, mononuclear cells.", "content": "When monocytes had differentiated to macrophages during 8 days of culture in vitro without being exposed to steroids, neither the engulfement nor the digestion step of phagocytosis was found to be influenced by cortisol or the other steroids tested. This indicates that cortisol has no direct effect on the phagocytic function of macrophages in doses below 10(-1) mg/ml. Continuous exposure to cortisol during the period of differentiation resulted in a dose dependent inhibition of the differentiation of monocytes to macrophages. Testosterone, deoxycorticosterone and tetrahydrocortisol in concentration of 10(-1) mg/ml, tested in the same way were found to be toxic to the cells. In lower concentrations, however, these steroids were found to have no effect on the cultured cells. The impaired differentiation of monocytes is suggested as an additional explanation of the reduced number of macrophages appearing at the site of inflammation during cortisol treatment.", "contents": "The effect of steroids on differentiation and function of cultured, mononuclear cells. When monocytes had differentiated to macrophages during 8 days of culture in vitro without being exposed to steroids, neither the engulfement nor the digestion step of phagocytosis was found to be influenced by cortisol or the other steroids tested. This indicates that cortisol has no direct effect on the phagocytic function of macrophages in doses below 10(-1) mg/ml. Continuous exposure to cortisol during the period of differentiation resulted in a dose dependent inhibition of the differentiation of monocytes to macrophages. Testosterone, deoxycorticosterone and tetrahydrocortisol in concentration of 10(-1) mg/ml, tested in the same way were found to be toxic to the cells. In lower concentrations, however, these steroids were found to have no effect on the cultured cells. The impaired differentiation of monocytes is suggested as an additional explanation of the reduced number of macrophages appearing at the site of inflammation during cortisol treatment."} {"id": "PMID:1266623", "title": "The interplay between target organ concentrations of lymphocytic choriomeningitis virus and cell mediated immunity in baby mice.", "content": "Circumstantial evidence has been presented which supports the view that the fatal LCM virus infection is due to an immunological conflict in the host animal. Hitherto, this outcome of the infection has only been observed in intracerebrally infected mice. In the present study, the intraperitoneal infection in young mice was investigated and the results revealed a new example of this immunological conflict. In mice infected a few days after birth, concentrations of the virus in the brain are high, while the CMI response is non-measurable. If the infection is induced when the mice are 28 days old or more, there is little virus in the CNS, but a strong CMI response can be demonstrated. All the mice in these two age groups survive. If mice are infected when they are 17-19 days old, however, they raise a moderate CMI response nine days after infection and, at the same time, their brains contain virus in high titres. The mortality among mice infected at this age is 100%, indicating that this combination is fatal. The lives of these animals can be saved by anti theta serum or if they are transplanted with syngeneic lymphoid cells sensitized to LCM virus. Our results strongly suggest an interplay between, on the one hand, the spread and the magnitude of the virus infection in the brain and, on the other, the cell mediated immune response. This interplay seems to be decisive for the clinical outcome of the LCM infection in mice.", "contents": "The interplay between target organ concentrations of lymphocytic choriomeningitis virus and cell mediated immunity in baby mice. Circumstantial evidence has been presented which supports the view that the fatal LCM virus infection is due to an immunological conflict in the host animal. Hitherto, this outcome of the infection has only been observed in intracerebrally infected mice. In the present study, the intraperitoneal infection in young mice was investigated and the results revealed a new example of this immunological conflict. In mice infected a few days after birth, concentrations of the virus in the brain are high, while the CMI response is non-measurable. If the infection is induced when the mice are 28 days old or more, there is little virus in the CNS, but a strong CMI response can be demonstrated. All the mice in these two age groups survive. If mice are infected when they are 17-19 days old, however, they raise a moderate CMI response nine days after infection and, at the same time, their brains contain virus in high titres. The mortality among mice infected at this age is 100%, indicating that this combination is fatal. The lives of these animals can be saved by anti theta serum or if they are transplanted with syngeneic lymphoid cells sensitized to LCM virus. Our results strongly suggest an interplay between, on the one hand, the spread and the magnitude of the virus infection in the brain and, on the other, the cell mediated immune response. This interplay seems to be decisive for the clinical outcome of the LCM infection in mice."} {"id": "PMID:1266619", "title": "Act of swallowing in the fixed larynx.", "content": "In a 16-year-old female, complete stenosis of the larynx and hypopharynx developed as a consequence of the ingestion of lye cristals. Supraglotic laryngectomy, plastic surgery of the hypopharynx and antethoracic oesophagus were performed and the upper aero-digestive tract reconstructed. The dilated larynx remained fixed by the surrounding fibrous tissue, but the sphincteric action of the mobile vocal cords was partly salvaged. In that condition, the act of swallowing could be reestablished. The pathophysiology of this new mechanism of swallowing is discussed.", "contents": "Act of swallowing in the fixed larynx. In a 16-year-old female, complete stenosis of the larynx and hypopharynx developed as a consequence of the ingestion of lye cristals. Supraglotic laryngectomy, plastic surgery of the hypopharynx and antethoracic oesophagus were performed and the upper aero-digestive tract reconstructed. The dilated larynx remained fixed by the surrounding fibrous tissue, but the sphincteric action of the mobile vocal cords was partly salvaged. In that condition, the act of swallowing could be reestablished. The pathophysiology of this new mechanism of swallowing is discussed."} {"id": "PMID:1266618", "title": "[Enzyme diagnosis of human parotid glands and its problems].", "content": "The gland-specific enzymes amylase, lysozyme and kallikrein the activities and their dependence on the speed of salivation were studied in normal persons. In these investigations the specification or standard ranges for differentiated secretion states is useful. In contrast to amylase activity, the activities of lysozyme and kallikrein weaken appreciably with increasing speed of salivation. The activity secreted, as measured in time units, increases. In the case of a diseased parotis, a comparison of enzyme activities with the standard values will show a significant reduction of lysozyme and amylase activity in the chronic processes. Acute inflammation affects the amylase activity slightly, but raises the lysozyme activity significantly. Parotid mixed tumours probably do not lead to any changes in the enzyme activities. The splitting up of amylase into isoenzymes by polyacrylamide gel electrophoresis and its possible importance for the diagnosis of pathological processes are discussed. First results of the splitting up of the parotid lysozyme are reported.", "contents": "[Enzyme diagnosis of human parotid glands and its problems]. The gland-specific enzymes amylase, lysozyme and kallikrein the activities and their dependence on the speed of salivation were studied in normal persons. In these investigations the specification or standard ranges for differentiated secretion states is useful. In contrast to amylase activity, the activities of lysozyme and kallikrein weaken appreciably with increasing speed of salivation. The activity secreted, as measured in time units, increases. In the case of a diseased parotis, a comparison of enzyme activities with the standard values will show a significant reduction of lysozyme and amylase activity in the chronic processes. Acute inflammation affects the amylase activity slightly, but raises the lysozyme activity significantly. Parotid mixed tumours probably do not lead to any changes in the enzyme activities. The splitting up of amylase into isoenzymes by polyacrylamide gel electrophoresis and its possible importance for the diagnosis of pathological processes are discussed. First results of the splitting up of the parotid lysozyme are reported."} {"id": "PMID:1266624", "title": "Fragments of immunoglobulins in human faeces.", "content": "Fab-fragments of IgG were easily demonstrated in extracts of faeces from healthy infants and children. Employing immunoelectrophoresis with antisera to whole human serum and to Fab-fragments of IgG, a marked precipitation line, likely to represent such fragments, was evident in the cathodal or gamma-region. Usually no precipitate was formed with antisera specific for gamma-heavy chains or Fc-fragments of IgG. Presumably IgG in the gut is partially destroyed before being excreted with faeces. Results of immunoelectrophoresis, gel filtration as well as polyacrylamide gel electrophoresis, using antisera to alpha-heavy chains, indicated the presence of fragments of IgA in some faecal extracts. Fragments of IgA could not be demonstrated in IgA-deficient patients, and no fragments of either class, or only traces of Fab-fragments of IgG, were found in agammaglobulinaemic patients. No antibody activity against rabbit erythrocytes was found in gel filtrations containing such fragments; any reaction was not observed either in the direct agglutination test or in a modified antiglobulin test.", "contents": "Fragments of immunoglobulins in human faeces. Fab-fragments of IgG were easily demonstrated in extracts of faeces from healthy infants and children. Employing immunoelectrophoresis with antisera to whole human serum and to Fab-fragments of IgG, a marked precipitation line, likely to represent such fragments, was evident in the cathodal or gamma-region. Usually no precipitate was formed with antisera specific for gamma-heavy chains or Fc-fragments of IgG. Presumably IgG in the gut is partially destroyed before being excreted with faeces. Results of immunoelectrophoresis, gel filtration as well as polyacrylamide gel electrophoresis, using antisera to alpha-heavy chains, indicated the presence of fragments of IgA in some faecal extracts. Fragments of IgA could not be demonstrated in IgA-deficient patients, and no fragments of either class, or only traces of Fab-fragments of IgG, were found in agammaglobulinaemic patients. No antibody activity against rabbit erythrocytes was found in gel filtrations containing such fragments; any reaction was not observed either in the direct agglutination test or in a modified antiglobulin test."} {"id": "PMID:1266620", "title": "Middle ear transmission losses caused by tympanic membrane perforations in cats.", "content": "Losses (determined by measuring microphonic responses) were essentially identical, regardless of whether produced by admittance of sound into the middle ear via perforations in the tympanic membrane (TM) or in the bulla. With SPLs monitored directly at the TM, losses increased at 12 dB/oct with inverse frequency for f less than 1 kHz, a pattern determined by the changes in the (calculated) net sound pressure acting from front and back on the TM. Clinically, hearing losses due to TM perforations are frequency-independent. The difference between the two situations has mainly to do with the use of precalibrated SPLs in Clinical Audiometry.", "contents": "Middle ear transmission losses caused by tympanic membrane perforations in cats. Losses (determined by measuring microphonic responses) were essentially identical, regardless of whether produced by admittance of sound into the middle ear via perforations in the tympanic membrane (TM) or in the bulla. With SPLs monitored directly at the TM, losses increased at 12 dB/oct with inverse frequency for f less than 1 kHz, a pattern determined by the changes in the (calculated) net sound pressure acting from front and back on the TM. Clinically, hearing losses due to TM perforations are frequency-independent. The difference between the two situations has mainly to do with the use of precalibrated SPLs in Clinical Audiometry."} {"id": "PMID:1266625", "title": "The effect of steroids on adhesiveness, rosette-forming ability and survival of cultured, human mononuclear cells.", "content": "The effect of different steroids on human mononuclear blood cells during the first 90 minutes of culture in vitro was tested. Cortisol and testosterone were found to increase the ability of lymophocytes to adhere on plastic surfaces. None of the other steroids tested exhibited this effect. Cortisol and corticosterone were found to reduce the number of surviving macrophages in the culture dishes, tested 4 to 8 days after the exposure to the drugs. No lysis of mononuclear cells could be detected following addition of cortisol in doses up to 10(-1) mg/ml. The findings support the previous statements that human lymphocytes are more cortisol-resistant than those of mouse, rat and rabbit.", "contents": "The effect of steroids on adhesiveness, rosette-forming ability and survival of cultured, human mononuclear cells. The effect of different steroids on human mononuclear blood cells during the first 90 minutes of culture in vitro was tested. Cortisol and testosterone were found to increase the ability of lymophocytes to adhere on plastic surfaces. None of the other steroids tested exhibited this effect. Cortisol and corticosterone were found to reduce the number of surviving macrophages in the culture dishes, tested 4 to 8 days after the exposure to the drugs. No lysis of mononuclear cells could be detected following addition of cortisol in doses up to 10(-1) mg/ml. The findings support the previous statements that human lymphocytes are more cortisol-resistant than those of mouse, rat and rabbit."} {"id": "PMID:1266621", "title": "Morphological observations of immunobiology of laryngeal cancer. Evaluation of the defensive activity of immunocompetent cells present in tumour stroma.", "content": "A series of 104 patients with squamous cell carcinoma of the larynx was studied with regard to tumour-host interaction. Prognostic evaluation was based upon histologic grading and morphological evidence of host immune response, judged by the presence and degree of lymphocyte and plasma cell infiltration in tumour stroma. Histologic grade and lymphoplasma-cellular infiltration do correlate with the 5-year survival. The immune response, however, seems to be a favourable prognostic sign only for well differentiated tumours; in our series, all poorly differentiated neoplasms showed minimal or no cellular response. The survival rate increases with the increasing intensity of cellular response within each class of tumour cell differentiation. Small lymphocytes are the basic elements of cell-mediated immune response. After tumour antigenic stimulation they change into immunoblasts which in turn would produce \"committed\" lymphocytes which would recognize and destroy tumour cells.", "contents": "Morphological observations of immunobiology of laryngeal cancer. Evaluation of the defensive activity of immunocompetent cells present in tumour stroma. A series of 104 patients with squamous cell carcinoma of the larynx was studied with regard to tumour-host interaction. Prognostic evaluation was based upon histologic grading and morphological evidence of host immune response, judged by the presence and degree of lymphocyte and plasma cell infiltration in tumour stroma. Histologic grade and lymphoplasma-cellular infiltration do correlate with the 5-year survival. The immune response, however, seems to be a favourable prognostic sign only for well differentiated tumours; in our series, all poorly differentiated neoplasms showed minimal or no cellular response. The survival rate increases with the increasing intensity of cellular response within each class of tumour cell differentiation. Small lymphocytes are the basic elements of cell-mediated immune response. After tumour antigenic stimulation they change into immunoblasts which in turn would produce \"committed\" lymphocytes which would recognize and destroy tumour cells."} {"id": "PMID:1266626", "title": "Evaluation of three reverse passive haemagglutination methods and two radioimmunoassay tests to be used for the detection of hepatitis B surface antigen.", "content": "Sensitivity and specificity of three reverse passive haemagglutination (RPHA) methods (Hepanosticon, Hepatest and Auscell) and of two solid-phase radioimmunoassays (RIA) (Austria-125 and Ausria II-125), all phase 3 tests for hepatitis B surface antigen (HBSAg), were compared with the sensitivity and specificity of an immunoelectroosmophoresis (IEOP) technique. By titration experiments the RPHA methods were shown to be 5-20 times more sensitive than the IEOP test, while RIA detected 5-10 times lower concentrations of antigen than the most sensitive RPHA test. In a study of sera drawn consecutively from patients with hepatitis B infections, the increased sensitivity of the test methods was according to the following order: IEOP, Hepanosticon, Hepatest, Ausria-125, Auscell, Ausria II-125. There were significant differences between all the methods except for that between Ausria-125 and Auscell. IEOP did not detect any false positives. If, however, RPHA tests were used, the incidence of nonspecific positive reactions would be in the range 0.5%-0.9%. The advantages of the individual test methods are discussed.", "contents": "Evaluation of three reverse passive haemagglutination methods and two radioimmunoassay tests to be used for the detection of hepatitis B surface antigen. Sensitivity and specificity of three reverse passive haemagglutination (RPHA) methods (Hepanosticon, Hepatest and Auscell) and of two solid-phase radioimmunoassays (RIA) (Austria-125 and Ausria II-125), all phase 3 tests for hepatitis B surface antigen (HBSAg), were compared with the sensitivity and specificity of an immunoelectroosmophoresis (IEOP) technique. By titration experiments the RPHA methods were shown to be 5-20 times more sensitive than the IEOP test, while RIA detected 5-10 times lower concentrations of antigen than the most sensitive RPHA test. In a study of sera drawn consecutively from patients with hepatitis B infections, the increased sensitivity of the test methods was according to the following order: IEOP, Hepanosticon, Hepatest, Ausria-125, Auscell, Ausria II-125. There were significant differences between all the methods except for that between Ausria-125 and Auscell. IEOP did not detect any false positives. If, however, RPHA tests were used, the incidence of nonspecific positive reactions would be in the range 0.5%-0.9%. The advantages of the individual test methods are discussed."} {"id": "PMID:1266627", "title": "Human colostral IgA interacting with staphylococcal protein A.", "content": "Human colostral IgA from three apparently healthy mothers were all divided into protein A reactive and protein A non-reactive fractions on a Sepharose-protein A column. The reactive fractions, giving no direct precipitation but co-precipitations, were found to interact with protein A through the Fc-region.", "contents": "Human colostral IgA interacting with staphylococcal protein A. Human colostral IgA from three apparently healthy mothers were all divided into protein A reactive and protein A non-reactive fractions on a Sepharose-protein A column. The reactive fractions, giving no direct precipitation but co-precipitations, were found to interact with protein A through the Fc-region."} {"id": "PMID:1266628", "title": "Tumor Fc receptors and tumor-associated immunoglobulins.", "content": "Tissue sections and cell suspensions from ten malignant tumors were tested for Fc receptors using sheep erythrocytes sensitized by rabbit IgG antibodies. Surface bound IgG on cells from the same tumors were estimated using an antiglobulin consumption test with 125I labelled human IgG as reference. The amount of IgG present per 10(6) cells varied from less than 100 ng to approximately 600 ng. When these amounts of IgG were plotted against the Fc receptor activity of corresponding tumors, seven of the tumors were distributed along a line showing an inverse linear relationship; i.e. tumors with large amounts of IgG on their cell surfaces had the lowest Fc reactivity and vice versa. Cells from three of the tumors had lower amounts of IgG on their surface than expected from this relationship. However, the lack of correlation could be explained by the focal distribution of the Fc positive tissue within non-reactive tissue. The cells from these areas presumably carry less IgG on their surface and thereby reduce the quantity of IgG calculated per 10(6) cells. Prolonged washing of tumor sections resulted in stronger Fc receptor activity, and correspondingly washed cells had lower amount of IgG on their surface. Presumably the Fc receptor can bind IgG in vivo.", "contents": "Tumor Fc receptors and tumor-associated immunoglobulins. Tissue sections and cell suspensions from ten malignant tumors were tested for Fc receptors using sheep erythrocytes sensitized by rabbit IgG antibodies. Surface bound IgG on cells from the same tumors were estimated using an antiglobulin consumption test with 125I labelled human IgG as reference. The amount of IgG present per 10(6) cells varied from less than 100 ng to approximately 600 ng. When these amounts of IgG were plotted against the Fc receptor activity of corresponding tumors, seven of the tumors were distributed along a line showing an inverse linear relationship; i.e. tumors with large amounts of IgG on their cell surfaces had the lowest Fc reactivity and vice versa. Cells from three of the tumors had lower amounts of IgG on their surface than expected from this relationship. However, the lack of correlation could be explained by the focal distribution of the Fc positive tissue within non-reactive tissue. The cells from these areas presumably carry less IgG on their surface and thereby reduce the quantity of IgG calculated per 10(6) cells. Prolonged washing of tumor sections resulted in stronger Fc receptor activity, and correspondingly washed cells had lower amount of IgG on their surface. Presumably the Fc receptor can bind IgG in vivo."} {"id": "PMID:1266629", "title": "Influence of antibodies and thermolabile serum factors on the bactericidal activity of human neutrophil granulocytes.", "content": "The influence of serum natibodies and thermolabile serum factors on the intracellular killing of Staphylococcus aureus by neutrophil granulocytes has been examined using a method which facilitates a precise in vitro evaluation of the phagocytic and bactericidal activities of human polymorphonuclear leucocytes. The bactericidal activity of the granulocytes was significantly less pronounced in the presence of serum absorbed with Staph. aureus or inactivated at 56 degrees C for 30 minutes than in the presence of untreated serum. Specific antibodies seemed to stimulate the intracellular killing of bacteria more than thermolabile serum factors.", "contents": "Influence of antibodies and thermolabile serum factors on the bactericidal activity of human neutrophil granulocytes. The influence of serum natibodies and thermolabile serum factors on the intracellular killing of Staphylococcus aureus by neutrophil granulocytes has been examined using a method which facilitates a precise in vitro evaluation of the phagocytic and bactericidal activities of human polymorphonuclear leucocytes. The bactericidal activity of the granulocytes was significantly less pronounced in the presence of serum absorbed with Staph. aureus or inactivated at 56 degrees C for 30 minutes than in the presence of untreated serum. Specific antibodies seemed to stimulate the intracellular killing of bacteria more than thermolabile serum factors."} {"id": "PMID:1266630", "title": "Influence of IgG, F(ab')2 and IgM on the phagocytic and bactericidal activities of human neutrophil granulocytes.", "content": "The phagocytosis and intracellular killing of Staphylococcus aureus by humans granulocytes in the presence of immunoglobulin preparations have been examined. Isolated IgG from pooled human serum induced phagocytosis and intracellular killing of bacteria. F(ab')2 fragments had no significant effect, indicating that the Fc piece of the IgG molecule is of importance not only for the phagocytosis but also for the intracellular killing of bacteria. Isolated IgM stimulated the phagocytosis to a minor extent, with no enhancement of the bactericidal activity.", "contents": "Influence of IgG, F(ab')2 and IgM on the phagocytic and bactericidal activities of human neutrophil granulocytes. The phagocytosis and intracellular killing of Staphylococcus aureus by humans granulocytes in the presence of immunoglobulin preparations have been examined. Isolated IgG from pooled human serum induced phagocytosis and intracellular killing of bacteria. F(ab')2 fragments had no significant effect, indicating that the Fc piece of the IgG molecule is of importance not only for the phagocytosis but also for the intracellular killing of bacteria. Isolated IgM stimulated the phagocytosis to a minor extent, with no enhancement of the bactericidal activity."} {"id": "PMID:1266631", "title": "Macrophage proliferation and activation during Toxoplasma gondii infection in mice: relationship to lymphocyte stimulation.", "content": "Macrophage proliferation and activation as well as lymphocyte stimulation in the peritoneal cavities of mice were investigated during the course of a Toxoplasma gondii (Beverly strain) infection. Macrophage proliferation had started already after day one and reached a first peak on day 2 (3H-thymidine labelling index approximately 6%). This proliferation was not accompanied by any notable lymphocyte stimulation. An equally high L.I. for macrophages was found after injection of 0.9% saline. From day 3-4 and peaking on day 7-11, a considerable blastoid transformation of lymphocytes occurred (maximum L.I. for lymphoid cells approximately 20% on day 7). In parallel with this blastoid response, a substantial macrophage proliferation took place (L.I. approximately 8%). Large numbers of activated macrophages also appeared during this period, DNA synthesizing cells were found even among the most highly activated macrophages. The results indicated that the early and the late macrophage proliferations were stimulated by different mechanisms.", "contents": "Macrophage proliferation and activation during Toxoplasma gondii infection in mice: relationship to lymphocyte stimulation. Macrophage proliferation and activation as well as lymphocyte stimulation in the peritoneal cavities of mice were investigated during the course of a Toxoplasma gondii (Beverly strain) infection. Macrophage proliferation had started already after day one and reached a first peak on day 2 (3H-thymidine labelling index approximately 6%). This proliferation was not accompanied by any notable lymphocyte stimulation. An equally high L.I. for macrophages was found after injection of 0.9% saline. From day 3-4 and peaking on day 7-11, a considerable blastoid transformation of lymphocytes occurred (maximum L.I. for lymphoid cells approximately 20% on day 7). In parallel with this blastoid response, a substantial macrophage proliferation took place (L.I. approximately 8%). Large numbers of activated macrophages also appeared during this period, DNA synthesizing cells were found even among the most highly activated macrophages. The results indicated that the early and the late macrophage proliferations were stimulated by different mechanisms."} {"id": "PMID:1266632", "title": "Acute disseminated phycomycosis in a patient with impaired neutrophil granulocyte function.", "content": "A 13-year-old girl with no previously known predisposing disease developed phycomycosis involving the left lung, pleura and shoulder, the left side of the neck, the left thigh, the kidneys and the brain. Prolonged amphotericin B therapy resulted in clinical improvement, but the disease was wide-spread when the patient died 5 months after debut of symptoms from a subarachnoid haemorrhage due to fungal destruction of the basilar artery. During hospitalization, a marked reduction in the bactericidal activity of circulating neutrophil granulocytes was repeatedly demonstrated and the endotoxin stimulated nitroblu tetrazolium test was negative. Together with the demonstration of granuloma formation and the accumulation of lipid-laden histiocytes in the spleen, lymph nodes, bone marrow and the thymus, these findings indicate that the patient had a less severe form of chronic granulomatous disease.", "contents": "Acute disseminated phycomycosis in a patient with impaired neutrophil granulocyte function. A 13-year-old girl with no previously known predisposing disease developed phycomycosis involving the left lung, pleura and shoulder, the left side of the neck, the left thigh, the kidneys and the brain. Prolonged amphotericin B therapy resulted in clinical improvement, but the disease was wide-spread when the patient died 5 months after debut of symptoms from a subarachnoid haemorrhage due to fungal destruction of the basilar artery. During hospitalization, a marked reduction in the bactericidal activity of circulating neutrophil granulocytes was repeatedly demonstrated and the endotoxin stimulated nitroblu tetrazolium test was negative. Together with the demonstration of granuloma formation and the accumulation of lipid-laden histiocytes in the spleen, lymph nodes, bone marrow and the thymus, these findings indicate that the patient had a less severe form of chronic granulomatous disease."} {"id": "PMID:1266654", "title": "Spinal cord vascularity. I. Extraspinal sources of spinal cord arteries in man.", "content": "The arrangement of extraspinal sources of the spinal cord arterial supply in man is more complicated than previously described, especially with regard to the origin and branching of the aortic segmental arteries. The fact that other arteries in the neck than the vertebral artery, such as the costo-cervical trunk and the ascending cervical artery may contribute to the supply of the cervical cord is confirmed, and also the occurrence of two or more spinal branches from different sources entering the same intervertebral foramen. Frequent occurrence of two or more segmental arteries arising from a common stem and variations in the branching of the subcostal arteries were found; their functional significance on the spinal cord circulation is not known. The fact that no significant anterior root artery was ever seen at the level of the vascular anomaly suggests that the anomaly is of no clinical importance. Nevertheless, obstruction of a common stem entail the risk of spinal cord infarction due to involvement of an important posterior root artery. On the other hand, the spinal cord seems to be fairly well protected against ischaemic injury following limited interference with the extraspinal arteries due to a profuse supply of intra- and extraspinal collaterals.", "contents": "Spinal cord vascularity. I. Extraspinal sources of spinal cord arteries in man. The arrangement of extraspinal sources of the spinal cord arterial supply in man is more complicated than previously described, especially with regard to the origin and branching of the aortic segmental arteries. The fact that other arteries in the neck than the vertebral artery, such as the costo-cervical trunk and the ascending cervical artery may contribute to the supply of the cervical cord is confirmed, and also the occurrence of two or more spinal branches from different sources entering the same intervertebral foramen. Frequent occurrence of two or more segmental arteries arising from a common stem and variations in the branching of the subcostal arteries were found; their functional significance on the spinal cord circulation is not known. The fact that no significant anterior root artery was ever seen at the level of the vascular anomaly suggests that the anomaly is of no clinical importance. Nevertheless, obstruction of a common stem entail the risk of spinal cord infarction due to involvement of an important posterior root artery. On the other hand, the spinal cord seems to be fairly well protected against ischaemic injury following limited interference with the extraspinal arteries due to a profuse supply of intra- and extraspinal collaterals."} {"id": "PMID:1266655", "title": "Kinematic analysis of experimentally provoked scoliosis in pigs with Roentgen stereophotogrammetry.", "content": "A three-dimensional method to analyse the kinematics of the spine has been applied to four pigs with experimentally provoked scoliosis. The advantages and limitations of the method are discussed and some interesting facts concerning the provoked curves are emphasized.", "contents": "Kinematic analysis of experimentally provoked scoliosis in pigs with Roentgen stereophotogrammetry. A three-dimensional method to analyse the kinematics of the spine has been applied to four pigs with experimentally provoked scoliosis. The advantages and limitations of the method are discussed and some interesting facts concerning the provoked curves are emphasized."} {"id": "PMID:1266656", "title": "Secretin and epinephrine combined in celiac angiography.", "content": "Celiac angiography was performed in 39 patients without pharmaceuticals, with epinephrine or secretin alone and with secretin and epinephrine combined. With secretin, and especially with secretin together with epinephrine the visibility of pancreatic arteries, capillaries and veins increased with a consequent improvement in information. Normal small veins such as the choledochal and the pancreaticoduodenal veins have proved to be of great diagnostic value. With secretin and epinephrine combined abnormal veins and nearly always abnormal capillaries became contrast filled in malignancy of the pancreas.", "contents": "Secretin and epinephrine combined in celiac angiography. Celiac angiography was performed in 39 patients without pharmaceuticals, with epinephrine or secretin alone and with secretin and epinephrine combined. With secretin, and especially with secretin together with epinephrine the visibility of pancreatic arteries, capillaries and veins increased with a consequent improvement in information. Normal small veins such as the choledochal and the pancreaticoduodenal veins have proved to be of great diagnostic value. With secretin and epinephrine combined abnormal veins and nearly always abnormal capillaries became contrast filled in malignancy of the pancreas."} {"id": "PMID:1266657", "title": "Hemangioma of the liver. Report of two cases.", "content": "Two cases of hepatic hemangiomas are described diagnosed by angiography and controlled by repeat angiography after 2.5 and 6 years, respectively. The radiologic appearance is described and although it varies, angiography must be considered the safest method of diagnosis; biopsy is contraindicated. Steroid therapy seems to be a possible mode of treatment.", "contents": "Hemangioma of the liver. Report of two cases. Two cases of hepatic hemangiomas are described diagnosed by angiography and controlled by repeat angiography after 2.5 and 6 years, respectively. The radiologic appearance is described and although it varies, angiography must be considered the safest method of diagnosis; biopsy is contraindicated. Steroid therapy seems to be a possible mode of treatment."} {"id": "PMID:1266658", "title": "Coronary angiography with diatrizoate and metrizamide. Comparison of ionic and non-ionic contrast medium effect on coronary blood flow in dogs.", "content": "The non-ionic contrast medium metrizamide produced a smaller coronary flow increase than the ionic medium diatrizoate after injection into the main left coronary artery in dogs and had also a shorter transit time through the coronary vessels. The coronary veins were better filled with metrizamide. The reduced coronary flow effects of metrizamide compared to ionic contrast medium and the improved venous filling makes metrizamide a favorable contrast material for use in coronary angiography.", "contents": "Coronary angiography with diatrizoate and metrizamide. Comparison of ionic and non-ionic contrast medium effect on coronary blood flow in dogs. The non-ionic contrast medium metrizamide produced a smaller coronary flow increase than the ionic medium diatrizoate after injection into the main left coronary artery in dogs and had also a shorter transit time through the coronary vessels. The coronary veins were better filled with metrizamide. The reduced coronary flow effects of metrizamide compared to ionic contrast medium and the improved venous filling makes metrizamide a favorable contrast material for use in coronary angiography."} {"id": "PMID:1266659", "title": "Contrast media: quantitative criteria for designing compounds with low toxicity.", "content": "Toxicity of contrast media that are ionized iodobenzoic acids or their derivatives is highly correlated with lipid solubility, as measured by the octanol/water partition coefficient. New contrast media have been designed with lower lipid solubility than media in current use, taking into account the additive-constitutive nature of the partition coefficient of an organic compound. If these contrast media are chemically stable, they should also be less toxic. It remains to be tested whether the relation between clinical toxicity and lipid solubility applies to non-ionized contrast media as well.", "contents": "Contrast media: quantitative criteria for designing compounds with low toxicity. Toxicity of contrast media that are ionized iodobenzoic acids or their derivatives is highly correlated with lipid solubility, as measured by the octanol/water partition coefficient. New contrast media have been designed with lower lipid solubility than media in current use, taking into account the additive-constitutive nature of the partition coefficient of an organic compound. If these contrast media are chemically stable, they should also be less toxic. It remains to be tested whether the relation between clinical toxicity and lipid solubility applies to non-ionized contrast media as well."} {"id": "PMID:1266660", "title": "Effect of epinephrine on the contractions in the normal renal pelvis in man. A cineradiographic investigation.", "content": "In 22 normal subjects a marked increase in the frequency and degree of contractions of the renal pelvis occurred after injections of 6 to 10 mug of epinephrine into the renal artery. Such injections may be used to increase the diagnostic value of cineradiography of the renal pelvis.", "contents": "Effect of epinephrine on the contractions in the normal renal pelvis in man. A cineradiographic investigation. In 22 normal subjects a marked increase in the frequency and degree of contractions of the renal pelvis occurred after injections of 6 to 10 mug of epinephrine into the renal artery. Such injections may be used to increase the diagnostic value of cineradiography of the renal pelvis."} {"id": "PMID:1266661", "title": "Plasma renin activity and hypertensive organ manifestations in 50-year-old males.", "content": "From a screening examination in a randomly selected third of the 50-year-old male population in G\u00f6teborg, Sweden, a 10% subsample was selected as a reference group (n=80). All untreated persons with SBP greater than 175 or DBP greater than 115 mmHg on two separate occasions made up the hypertension group (n=35). The reference group and the hypertension group were subjected to the same investigations, including BP measurement before and after rest and determination of plasma renin activity (PRA), urinary sodium and norepinephrine excretion and GFR. Plasma renin activity was approximately normally distributed in both the reference and the hypertension group. Mean values were 0.78 +/- 0.18 and 0.65 +/- 0.17 ng/ml/h respectively, the difference being almost statistically significant (0.10 greater than p greater than 0.05). There was no difference with respect to sodium excretion between the reference group and the hypertension group. In the reference group, heart rate was positively correlated to PRA and to urinary norepinephrine excretion during the day. No linear correlation between PAR and BP was found, either in the reference group, or in the hypertension group. Sodium excretion during the day was positively correlated to GFR in the hypertension group, but not in the reference group. Compared to hypertensives with normal or high sodium excretion during the day, the hypertensives with low sodium excretion during the day were characterized by a higher BP, a lower GFR and a reversed diurnal rhythm of urine excretion. Thus, low sodium excretion seemed to indicate more severe hypertension with increased renal resistance during the day. The hypertension group was also divided with regard to sodium excretion into a low, normal and high renin group. The low renin group had the lowest GFR and with rising renin group (from low via normal to high) there was a significant increase in GFR and a significant decrease in resting BP. The results indicate that low renin hypertension is not a more mild, but indeed rather a more severe form of hypertension.", "contents": "Plasma renin activity and hypertensive organ manifestations in 50-year-old males. From a screening examination in a randomly selected third of the 50-year-old male population in G\u00f6teborg, Sweden, a 10% subsample was selected as a reference group (n=80). All untreated persons with SBP greater than 175 or DBP greater than 115 mmHg on two separate occasions made up the hypertension group (n=35). The reference group and the hypertension group were subjected to the same investigations, including BP measurement before and after rest and determination of plasma renin activity (PRA), urinary sodium and norepinephrine excretion and GFR. Plasma renin activity was approximately normally distributed in both the reference and the hypertension group. Mean values were 0.78 +/- 0.18 and 0.65 +/- 0.17 ng/ml/h respectively, the difference being almost statistically significant (0.10 greater than p greater than 0.05). There was no difference with respect to sodium excretion between the reference group and the hypertension group. In the reference group, heart rate was positively correlated to PRA and to urinary norepinephrine excretion during the day. No linear correlation between PAR and BP was found, either in the reference group, or in the hypertension group. Sodium excretion during the day was positively correlated to GFR in the hypertension group, but not in the reference group. Compared to hypertensives with normal or high sodium excretion during the day, the hypertensives with low sodium excretion during the day were characterized by a higher BP, a lower GFR and a reversed diurnal rhythm of urine excretion. Thus, low sodium excretion seemed to indicate more severe hypertension with increased renal resistance during the day. The hypertension group was also divided with regard to sodium excretion into a low, normal and high renin group. The low renin group had the lowest GFR and with rising renin group (from low via normal to high) there was a significant increase in GFR and a significant decrease in resting BP. The results indicate that low renin hypertension is not a more mild, but indeed rather a more severe form of hypertension."} {"id": "PMID:1266662", "title": "Hemodynamic effect of pindolol in essential hypertension with special reference to the resistance and capacitance vessels of the forearm.", "content": "Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, have been studied at rest and during work before and after on average 8 weeks oral treatment with a beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, heart rate and cardiac output both at rest and during work. The systemic vascular resistance and the forearm vascular resistance decreased significantly after and during work, respectively. Forearm venous tone was significantly decreased at rest, during and after work. The plasma renin activity decreased. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: 1) a negative chronotropic effect on the heart, 2) a decrease in peripheral vascular resistance, and 3) an increase in vascular capacitance affecting the venous return.", "contents": "Hemodynamic effect of pindolol in essential hypertension with special reference to the resistance and capacitance vessels of the forearm. Ten patients, mean age 48 years, with essential hypertension of stage I and II according to the WHO classification, have been studied at rest and during work before and after on average 8 weeks oral treatment with a beta-adrenergic blocking agent, pindolol. The pindolol treatment caused a significant decrease in the systemic systolic and diastolic blood pressure, heart rate and cardiac output both at rest and during work. The systemic vascular resistance and the forearm vascular resistance decreased significantly after and during work, respectively. Forearm venous tone was significantly decreased at rest, during and after work. The plasma renin activity decreased. Three mechanisms seem to be involved in the antihypertensive effect of pindolol: 1) a negative chronotropic effect on the heart, 2) a decrease in peripheral vascular resistance, and 3) an increase in vascular capacitance affecting the venous return."} {"id": "PMID:1266663", "title": "A blood pressure information campaign including mass screening for hypertension in Copenhagen Supermarkets.", "content": "During its \"Heart-week\" in Feb. 1975, the Danish Heart Foundation drew the attention of the public to the importance of blood pressure measurements as a vital part of health control and prevention. In all, 24 thousand men and women attending supermarkets in Copenhagen took advantage of an offer to have their BP checked. 23% of the screened, who had systolic BP greater than or equal to age+110 (and this sum exceeded 145) and/or diastolic BP greater than or equal to 100 mmHg for all ages, were advised to contact a general practitioner for further evaluation. The campaign showed that it is possible to measure BP and obtain reliable results in an easy, quick, inexpensive and unorthodox way accepted by a public accustomed to free medical care.", "contents": "A blood pressure information campaign including mass screening for hypertension in Copenhagen Supermarkets. During its \"Heart-week\" in Feb. 1975, the Danish Heart Foundation drew the attention of the public to the importance of blood pressure measurements as a vital part of health control and prevention. In all, 24 thousand men and women attending supermarkets in Copenhagen took advantage of an offer to have their BP checked. 23% of the screened, who had systolic BP greater than or equal to age+110 (and this sum exceeded 145) and/or diastolic BP greater than or equal to 100 mmHg for all ages, were advised to contact a general practitioner for further evaluation. The campaign showed that it is possible to measure BP and obtain reliable results in an easy, quick, inexpensive and unorthodox way accepted by a public accustomed to free medical care."} {"id": "PMID:1266664", "title": "Detection and characterization of middle-aged men with hypertension.", "content": "In a health examination survey of more than 2,000 middle-aged men the prevalence of hypertension, defined as supine DBP greater than or equal to 105 mmHg and including those on treatment, was 7.5%. Half of the hypertensives were untreated. A satisfactory BP control was present in 27.6% of the total hypertensive population. Untreated hypertensives had a higher relative body weight and a greater skinfold thickness, indicating a greater degree of obesity, than a population sample from the same survey. They also had more hyperuricaemia, hypertriglyceridaemia and hyperinsulinaemia, fasting as well as during i.v. glucose tolerance test. However, when the hypertensives were compared to normotensive, weight-matched controls, most of these differences were eliminated. The findings indicate that the metabolic disturbances in hypertensives are associated with overweight and suggest that weight reduction might be beneficial not only for the BP but also for correcting the metabolic pattern.", "contents": "Detection and characterization of middle-aged men with hypertension. In a health examination survey of more than 2,000 middle-aged men the prevalence of hypertension, defined as supine DBP greater than or equal to 105 mmHg and including those on treatment, was 7.5%. Half of the hypertensives were untreated. A satisfactory BP control was present in 27.6% of the total hypertensive population. Untreated hypertensives had a higher relative body weight and a greater skinfold thickness, indicating a greater degree of obesity, than a population sample from the same survey. They also had more hyperuricaemia, hypertriglyceridaemia and hyperinsulinaemia, fasting as well as during i.v. glucose tolerance test. However, when the hypertensives were compared to normotensive, weight-matched controls, most of these differences were eliminated. The findings indicate that the metabolic disturbances in hypertensives are associated with overweight and suggest that weight reduction might be beneficial not only for the BP but also for correcting the metabolic pattern."} {"id": "PMID:1266665", "title": "Treatment of hypertension in middle-aged men. A feasibility study in a community.", "content": "In a health examination survey of 2322 middle-aged men the prevalence of hypertension, defined as supine DBP greater than or equal to 105 mmHg and including those on treatment, was 7.5%. All untreated and those inadequately treated were invited to a hypertension clinic. One year's treatment in 86 men achieved a BP reduction of 29/17 mmHg in supine and 27/16 mmHg in erect position. This reduction was maintained for a three-year period and considered satisfactory in 80% of subjects. Propranolol, alone or in combination with other agents, was used in more than 80% of the cases. Special considerations in treating asymptomatic individuals are discussed.", "contents": "Treatment of hypertension in middle-aged men. A feasibility study in a community. In a health examination survey of 2322 middle-aged men the prevalence of hypertension, defined as supine DBP greater than or equal to 105 mmHg and including those on treatment, was 7.5%. All untreated and those inadequately treated were invited to a hypertension clinic. One year's treatment in 86 men achieved a BP reduction of 29/17 mmHg in supine and 27/16 mmHg in erect position. This reduction was maintained for a three-year period and considered satisfactory in 80% of subjects. Propranolol, alone or in combination with other agents, was used in more than 80% of the cases. Special considerations in treating asymptomatic individuals are discussed."} {"id": "PMID:1266666", "title": "Interstitial nephritis with acute renal failure following cardiac surgery and treatment with methicillin.", "content": "Six patients developed acute renal failure 13-19 days after cardiac surgery with extracorporeal circulation. None of the patients had suffered from postoperative hypotension; slight hemolysis was present for only 1-2 days post-operatively. Acute renal failure lasted for 11-80 days in four patients. In two patients creatinine clearance stabilized at reduced values. Seven renal biopsies from the six patients showed severe acute interstitial nephritis with mononuclear cellular infiltration and distal tubular damage. No immune deposits were detected in glomeruli or tubular basement membrane. All six patients had been treated prophylactically with methicillin and the acute renal disease was probably elicited by this drug.", "contents": "Interstitial nephritis with acute renal failure following cardiac surgery and treatment with methicillin. Six patients developed acute renal failure 13-19 days after cardiac surgery with extracorporeal circulation. None of the patients had suffered from postoperative hypotension; slight hemolysis was present for only 1-2 days post-operatively. Acute renal failure lasted for 11-80 days in four patients. In two patients creatinine clearance stabilized at reduced values. Seven renal biopsies from the six patients showed severe acute interstitial nephritis with mononuclear cellular infiltration and distal tubular damage. No immune deposits were detected in glomeruli or tubular basement membrane. All six patients had been treated prophylactically with methicillin and the acute renal disease was probably elicited by this drug."} {"id": "PMID:1266667", "title": "The effect on serum enzymes of intramuscular injections of digoxin, bumetanide, pentazocine and isotonic sodium chloride.", "content": "Intramuscular injections of digoxin, bumetanide, pentazocine or isotonic sodium chloride have been given to 39 patients. We followed the serum concentrations of creatine kinase (CK), aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH) and LDH isoenzymes for 4 days. Ten patients receiving 500 mug digoxin showed a significant rise in CK, which lasted for 48 hours, and 6 of them had CK values exceeding the upper normal limit. Pentazocine in a dose of 30 mg given to 9 patients caused a significant rise in CK and LDH isoenzyme 1, but in no case did the level exceed the upper normal limit. No rise in ASAT or total LDH was found after digoxin and pentazocine injections. No changes in enzymes were discovered after bumetanide or isotonic sodium chloride. In the diagnostic evaluation of acute myocardial infarction, a moderate rise in CK must be assessed with caution when the patients have received i.m. injections of drugs with osmolarity and pH outside the physiological limits.", "contents": "The effect on serum enzymes of intramuscular injections of digoxin, bumetanide, pentazocine and isotonic sodium chloride. Intramuscular injections of digoxin, bumetanide, pentazocine or isotonic sodium chloride have been given to 39 patients. We followed the serum concentrations of creatine kinase (CK), aspartate aminotransferase (ASAT), lactate dehydrogenase (LDH) and LDH isoenzymes for 4 days. Ten patients receiving 500 mug digoxin showed a significant rise in CK, which lasted for 48 hours, and 6 of them had CK values exceeding the upper normal limit. Pentazocine in a dose of 30 mg given to 9 patients caused a significant rise in CK and LDH isoenzyme 1, but in no case did the level exceed the upper normal limit. No rise in ASAT or total LDH was found after digoxin and pentazocine injections. No changes in enzymes were discovered after bumetanide or isotonic sodium chloride. In the diagnostic evaluation of acute myocardial infarction, a moderate rise in CK must be assessed with caution when the patients have received i.m. injections of drugs with osmolarity and pH outside the physiological limits."} {"id": "PMID:1266668", "title": "Lysozyme activity in cerebrospinal fluid.", "content": "The concentration of lysozyme (LZM) in cerebrospinal fluid (CSF) has been studied in 148 patients to evaluate its possible significance in the differential diagnosis of various diseases affecting the central nervous system (CNS). In the control group only 3 of 45 patients had detectable LZM in their CSF, the highest value being 1.3 mug/ml. The diabetic and epileptic groups did not differ from the control group. Of 8 patients with primary intracranial tumours, 4 had raised CSF-LZM levels. Twenty of 23 uraemic patients had elevated CSF-LZM, the highest value being 3.3 mug/ml. The highest values were found in patients with bacterial meningitis, tuberculous meningitis and leptomeningitis due to Aspergillus. A positive correlation was found between CSF-LZM and protein concentrations. The measurement of LZM may be of value in the diagnosis of inflammatory processes affecting the CNS and in the diagnosis of certain intracranial tumours.", "contents": "Lysozyme activity in cerebrospinal fluid. The concentration of lysozyme (LZM) in cerebrospinal fluid (CSF) has been studied in 148 patients to evaluate its possible significance in the differential diagnosis of various diseases affecting the central nervous system (CNS). In the control group only 3 of 45 patients had detectable LZM in their CSF, the highest value being 1.3 mug/ml. The diabetic and epileptic groups did not differ from the control group. Of 8 patients with primary intracranial tumours, 4 had raised CSF-LZM levels. Twenty of 23 uraemic patients had elevated CSF-LZM, the highest value being 3.3 mug/ml. The highest values were found in patients with bacterial meningitis, tuberculous meningitis and leptomeningitis due to Aspergillus. A positive correlation was found between CSF-LZM and protein concentrations. The measurement of LZM may be of value in the diagnosis of inflammatory processes affecting the CNS and in the diagnosis of certain intracranial tumours."} {"id": "PMID:1266669", "title": "Recurrent and reversible cerebellar ataxia with concomitant episodes of hyperthyroidism: a new autoimmune syndrome.", "content": "A new disorder with possible autoimmune background is described in a 67-year-old man. He had experienced episodes of cerebellar ataxia induced by infections over the last 40 years. In 1963 he had thyrotoxicosis. The patient underwent bilateral subtotal thyroidectomy. Recently it has been possible to detect involvement also of his remaining thyroid gland, with findings compatible with hyperthyroidism concomitant with his cerebellar atixia.", "contents": "Recurrent and reversible cerebellar ataxia with concomitant episodes of hyperthyroidism: a new autoimmune syndrome. A new disorder with possible autoimmune background is described in a 67-year-old man. He had experienced episodes of cerebellar ataxia induced by infections over the last 40 years. In 1963 he had thyrotoxicosis. The patient underwent bilateral subtotal thyroidectomy. Recently it has been possible to detect involvement also of his remaining thyroid gland, with findings compatible with hyperthyroidism concomitant with his cerebellar atixia."} {"id": "PMID:1266673", "title": "Enhancing effect of radioresistant spleen cells on the primary immune response against sheep RBC by mouse spleen cells in vitro.", "content": "Irradiated spleen cells cultured for 3 days, caused a stimulation of the primary in vitro immune response by normal spleen cells. These irradiated spleen cells were fractionated by velocity sedimentation and the fractions were tested for their stimulating activity. Only the macrophage enriched fractions were found to cause stimulation. The macrophages in these fractions were stuffed with erythrocytes and dead cells. The fractions enriched in thymus derived cells, had no effect on the immune response. Irradiated spleen cells cultured for 24 hours caused inhibition. It has not yet been determined whether this inhibition was due to some transient change in the macrophage population during incubation. The stimulating effect by the irradiated spleen cells from SPF mice was strongly reduced, which at least partly could be ascribed to the naturally occurring low number of macrophages in the spleens of these mice.", "contents": "Enhancing effect of radioresistant spleen cells on the primary immune response against sheep RBC by mouse spleen cells in vitro. Irradiated spleen cells cultured for 3 days, caused a stimulation of the primary in vitro immune response by normal spleen cells. These irradiated spleen cells were fractionated by velocity sedimentation and the fractions were tested for their stimulating activity. Only the macrophage enriched fractions were found to cause stimulation. The macrophages in these fractions were stuffed with erythrocytes and dead cells. The fractions enriched in thymus derived cells, had no effect on the immune response. Irradiated spleen cells cultured for 24 hours caused inhibition. It has not yet been determined whether this inhibition was due to some transient change in the macrophage population during incubation. The stimulating effect by the irradiated spleen cells from SPF mice was strongly reduced, which at least partly could be ascribed to the naturally occurring low number of macrophages in the spleens of these mice."} {"id": "PMID:1266674", "title": "Relation of antigen-binding cells to immunological memory.", "content": "Priming of mice with a conjugate of HSA with sheep red cells induced a high level of memory to HSA, with very little antibody production (\"pure priming\"). HSA specific antigen binding cells in the spleens of the primed mice were assayed by means of a rosette technique, using HSA conjugated to donkey red cells. Rosette formation was almost completely inhibited by soluble HSA, thus confirming that the RFC were specific for this antigen. Spleens of primed mice contained up to 0.6% RFC, as compared to 0.08% HSA specific RFC in the spleens of non immunized animals. Suspensions enriched in rosettes (containing up to 16% RFC) were prepared by centrifugation on BSA density gradients. Adoptive transfer experiments showed that the rosette rich fraction contained all the memory cells. A marginal level of memory could be transferred to irradiated recipients with 3000 rosettes. A comparable degree of responsiveness to HSA could also be transferred with 70,000 RFC enriched from spleens of non immunized mice, but only when injected together with primed, RFC depleted spleen cells. Kinetic studies showed that the level of memory correlated well with the number of RFC up to two months after priming. The number of RFC decreased at later time intervals (though remaining higher than in controls at all times), without a corresponding decrease in the level of memory. A change in the quality of the memory cell with time is postulated.", "contents": "Relation of antigen-binding cells to immunological memory. Priming of mice with a conjugate of HSA with sheep red cells induced a high level of memory to HSA, with very little antibody production (\"pure priming\"). HSA specific antigen binding cells in the spleens of the primed mice were assayed by means of a rosette technique, using HSA conjugated to donkey red cells. Rosette formation was almost completely inhibited by soluble HSA, thus confirming that the RFC were specific for this antigen. Spleens of primed mice contained up to 0.6% RFC, as compared to 0.08% HSA specific RFC in the spleens of non immunized animals. Suspensions enriched in rosettes (containing up to 16% RFC) were prepared by centrifugation on BSA density gradients. Adoptive transfer experiments showed that the rosette rich fraction contained all the memory cells. A marginal level of memory could be transferred to irradiated recipients with 3000 rosettes. A comparable degree of responsiveness to HSA could also be transferred with 70,000 RFC enriched from spleens of non immunized mice, but only when injected together with primed, RFC depleted spleen cells. Kinetic studies showed that the level of memory correlated well with the number of RFC up to two months after priming. The number of RFC decreased at later time intervals (though remaining higher than in controls at all times), without a corresponding decrease in the level of memory. A change in the quality of the memory cell with time is postulated."} {"id": "PMID:1266676", "title": "Observations in vitro regarding the mechanism of the cell destruction by stimulated lymphocytes.", "content": "In contrast to other cells stimulated lymphocytes release substances probably cytotoxic which are incorporated by the target cells. The cellular material is released by tearing off parts of fine processes which the lymphocytes extend on to the surface of the target cells. This explains the before mentioned observations that the cell destruction mediated by lymphocytes depends absolutely on a close contact between the lymphocytes and the target cells.", "contents": "Observations in vitro regarding the mechanism of the cell destruction by stimulated lymphocytes. In contrast to other cells stimulated lymphocytes release substances probably cytotoxic which are incorporated by the target cells. The cellular material is released by tearing off parts of fine processes which the lymphocytes extend on to the surface of the target cells. This explains the before mentioned observations that the cell destruction mediated by lymphocytes depends absolutely on a close contact between the lymphocytes and the target cells."} {"id": "PMID:1266678", "title": "Immunomorphological lymph node processes in some cirrhogenic liver diseases.", "content": "Dynamics of the lymph node modifications as well as hepatic and immunoserological in various cirrhogenic hepatopathies have been studied on human and experimental material. Lymph nodes showed early and progressively immunomorphological reactions with maximum intensity in evolutive stages of certain cirrhoses. Such reactions as well as in other areas of reticulo-endothelial system are decreasing during the immunosuppressive treatment and in advanced stages of cirrhosis. The lymph nodes participation in the pathogenic mechanism of some cirrhogenic hepatopathies has been very little studied, whereas that of the liver and of the spleen has been more approached. Our previous investigations (1) have disclosed the existence of some chronic lymphadenites as well as reactional reticuloses on necroptic material from young cirrhotics. Equally, during some preliminary experimental studies (7) We remarked intense lymph node reactions even in incipient phases of cirrhoses, which fact stirred us up to examine them thoroughly.", "contents": "Immunomorphological lymph node processes in some cirrhogenic liver diseases. Dynamics of the lymph node modifications as well as hepatic and immunoserological in various cirrhogenic hepatopathies have been studied on human and experimental material. Lymph nodes showed early and progressively immunomorphological reactions with maximum intensity in evolutive stages of certain cirrhoses. Such reactions as well as in other areas of reticulo-endothelial system are decreasing during the immunosuppressive treatment and in advanced stages of cirrhosis. The lymph nodes participation in the pathogenic mechanism of some cirrhogenic hepatopathies has been very little studied, whereas that of the liver and of the spleen has been more approached. Our previous investigations (1) have disclosed the existence of some chronic lymphadenites as well as reactional reticuloses on necroptic material from young cirrhotics. Equally, during some preliminary experimental studies (7) We remarked intense lymph node reactions even in incipient phases of cirrhoses, which fact stirred us up to examine them thoroughly."} {"id": "PMID:1266688", "title": "Research on a new type of antiinsulin antibody in a diabetic female patient: the cytotoxic antibody. antiinsulin cytotoxic antibody.", "content": "A study was carried out on a diabetic patient showing allergy to insulin, with urticaria and Quincke's edema, apparently owing to sensitization with IgE antibodies. By means of a hyposensitizing treatment her allergy improved due to the building up of IgG protecting antibodies, but at the same time she showed resistance to insulin, probably owing to IgG antibodies as well. This suggest that caution should be exerted before applying hyposensitization with insulin on diabetic patients allergic to the hormone. We were able to describe on the same patient a type II sensitization caused by a cytotoxic antibody against insulin. It was shown that this antibody agglutinates leukocytes which had been previously incubated with insulin and damage occurred when complement was present. Those effects could be especifically inhibited when the antigen (insulin) was added to the medium. The antibody belongs to the IgG group and it acts both in vivo and in vitro. In the case under study, the cytotoxic antibody disappeared as soon as treatment with insulin was discontinued for a year, and reappeared when renewed. It does not seem to occur very frequently, for it was not found in 20 consecutive diabetic patients under insulin treatment.", "contents": "Research on a new type of antiinsulin antibody in a diabetic female patient: the cytotoxic antibody. antiinsulin cytotoxic antibody. A study was carried out on a diabetic patient showing allergy to insulin, with urticaria and Quincke's edema, apparently owing to sensitization with IgE antibodies. By means of a hyposensitizing treatment her allergy improved due to the building up of IgG protecting antibodies, but at the same time she showed resistance to insulin, probably owing to IgG antibodies as well. This suggest that caution should be exerted before applying hyposensitization with insulin on diabetic patients allergic to the hormone. We were able to describe on the same patient a type II sensitization caused by a cytotoxic antibody against insulin. It was shown that this antibody agglutinates leukocytes which had been previously incubated with insulin and damage occurred when complement was present. Those effects could be especifically inhibited when the antigen (insulin) was added to the medium. The antibody belongs to the IgG group and it acts both in vivo and in vitro. In the case under study, the cytotoxic antibody disappeared as soon as treatment with insulin was discontinued for a year, and reappeared when renewed. It does not seem to occur very frequently, for it was not found in 20 consecutive diabetic patients under insulin treatment."} {"id": "PMID:1266690", "title": "[House-dust allergens. II. Correlations of intradermal reactions of house-dust extract and extract of \"D. pteronyssinus\"].", "content": "In a previous study we had found a high correlation between the positive reaction to standard house dust and to a mites pool extract of 0.86. The study had indicated that the dominant mite found in standard house dust in Barcelona seemed to be D. pteronyssinus. We wished to further confirm this finding by comparing skin reactions to an extract of this mite with skin reactions to the city's dust. A dust extract (HDS-B) was prepared according to the Spieksma technique in a proportion of W/V 1/10 and diluted to 1/1,000 with the liquid of the extract. Extracts of D. pteronyssinus were prepared with a culture medium (HDM), diluted to 1/1,000,000 and a control of thc culture medium at 1/100. A study was made of 56 children suffering from asthma due to house dust, their ages ranging from 4-14 years. 19 were eliminated due to positive reactions to the control. Among the remaining 37 a skin-reaction to histamine ratio was established. The correlation coefficient found was 0.91, which is significant at a level of P less than 0.001. It is also noteworthy that of the nineteen children (33.9%) who reacted to the control, 10 (17.85%) of them reacted positively with at least 2-3 crosses, which leads us to think that human dander may act as a lesser allergen. We therefore conclude that: 1. D. pteronyssinus is the principal source of allergen in domestic dust. 2. The precise role of human skin dander needs to be clarified.", "contents": "[House-dust allergens. II. Correlations of intradermal reactions of house-dust extract and extract of \"D. pteronyssinus\"]. In a previous study we had found a high correlation between the positive reaction to standard house dust and to a mites pool extract of 0.86. The study had indicated that the dominant mite found in standard house dust in Barcelona seemed to be D. pteronyssinus. We wished to further confirm this finding by comparing skin reactions to an extract of this mite with skin reactions to the city's dust. A dust extract (HDS-B) was prepared according to the Spieksma technique in a proportion of W/V 1/10 and diluted to 1/1,000 with the liquid of the extract. Extracts of D. pteronyssinus were prepared with a culture medium (HDM), diluted to 1/1,000,000 and a control of thc culture medium at 1/100. A study was made of 56 children suffering from asthma due to house dust, their ages ranging from 4-14 years. 19 were eliminated due to positive reactions to the control. Among the remaining 37 a skin-reaction to histamine ratio was established. The correlation coefficient found was 0.91, which is significant at a level of P less than 0.001. It is also noteworthy that of the nineteen children (33.9%) who reacted to the control, 10 (17.85%) of them reacted positively with at least 2-3 crosses, which leads us to think that human dander may act as a lesser allergen. We therefore conclude that: 1. D. pteronyssinus is the principal source of allergen in domestic dust. 2. The precise role of human skin dander needs to be clarified."} {"id": "PMID:1266691", "title": "Kveim-test in patients suspected of sarcoidosis and in leprosy patients in a geographical area not yea investigated.", "content": "The Kveim-test was studied in a geographical area (S\u00e3o Paulo, Brazil) not yet investigated, and leprosy patients were also tested. One hundred and forty seven patients from a general hospital who had had the possibility of sarcoidosis, as a differential diagnosis, were tested with Kveim suspension. Another group of 13 patients with clinical and histological diagnosis of leprosy (10 with tuberculoid leprosy lepromin-positive and 3 with indetermined leprosy) was also tested with Kveim suspension. Sixteen Kveim-tests (10 per cent) with sarcoid granulomatous reaction revealed histologically were considered positive. Three patients with sarcoidosis for more than 3 years gave negative Kveim-test. Four patients with positive Kveim-test had respectively lymphosarcoma, Crohn's disease, lung fibrosis and concurrent tuberculosis infection. Nine positive Kveim-tests (5.6 per cent) were coincident with sarcoidosis. Thirteen leprosy patients (ten tuberculoid) gave negative Kveim-test.", "contents": "Kveim-test in patients suspected of sarcoidosis and in leprosy patients in a geographical area not yea investigated. The Kveim-test was studied in a geographical area (S\u00e3o Paulo, Brazil) not yet investigated, and leprosy patients were also tested. One hundred and forty seven patients from a general hospital who had had the possibility of sarcoidosis, as a differential diagnosis, were tested with Kveim suspension. Another group of 13 patients with clinical and histological diagnosis of leprosy (10 with tuberculoid leprosy lepromin-positive and 3 with indetermined leprosy) was also tested with Kveim suspension. Sixteen Kveim-tests (10 per cent) with sarcoid granulomatous reaction revealed histologically were considered positive. Three patients with sarcoidosis for more than 3 years gave negative Kveim-test. Four patients with positive Kveim-test had respectively lymphosarcoma, Crohn's disease, lung fibrosis and concurrent tuberculosis infection. Nine positive Kveim-tests (5.6 per cent) were coincident with sarcoidosis. Thirteen leprosy patients (ten tuberculoid) gave negative Kveim-test."} {"id": "PMID:1266700", "title": "Community screening for Tay-Sachs disease.", "content": "Tay-Sachs disease is a fatal genetic disease affecting Jewish infants of eastern European ancestry. While the disease may go unrecognized until nearly one year of age, death occurs by age three or four. Community screening programs have been organized to detect carriers of this autosomal recessive trait. Prenatal diagnosis now allows carrier couples to have normal children without the risk of having an affected child. These programs hopefully will serve as models for the future prevention of other genetic diseases.", "contents": "Community screening for Tay-Sachs disease. Tay-Sachs disease is a fatal genetic disease affecting Jewish infants of eastern European ancestry. While the disease may go unrecognized until nearly one year of age, death occurs by age three or four. Community screening programs have been organized to detect carriers of this autosomal recessive trait. Prenatal diagnosis now allows carrier couples to have normal children without the risk of having an affected child. These programs hopefully will serve as models for the future prevention of other genetic diseases."} {"id": "PMID:1266701", "title": "Anorexia nervosa.", "content": "Anorexia nervosa occurs predominantly in white, middle-class, adolescent females with perfectionistic tendencies. Their solution to the intense guilt induced by any sensory pleasure is to deny themselves the pleasure of eating. Amenorrhea is universal. Diagnostic criteria include a 25 percent weight loss. Therapies are long and involved different approaches. All recognize that food is the medicine for the body and that some form of supportive psychotherapy is the medicine for the mind.", "contents": "Anorexia nervosa. Anorexia nervosa occurs predominantly in white, middle-class, adolescent females with perfectionistic tendencies. Their solution to the intense guilt induced by any sensory pleasure is to deny themselves the pleasure of eating. Amenorrhea is universal. Diagnostic criteria include a 25 percent weight loss. Therapies are long and involved different approaches. All recognize that food is the medicine for the body and that some form of supportive psychotherapy is the medicine for the mind."} {"id": "PMID:1266708", "title": "Compliance: a problem in medical management.", "content": "The prevalence of noncompliance is underestimated and the role of the physician in promoting and inhibiting complicance is not often recognized. Physicians accept the need for patient education but do not accept responsibility for the patient's compliance. The disease denial/rationalization syndrome is a useful label for emotional resistance to the treatment program. An important factor is the extent to which the physician seeks to ascertain compliance. Compliance-gaining strategies must be applied with tact and flexibility.", "contents": "Compliance: a problem in medical management. The prevalence of noncompliance is underestimated and the role of the physician in promoting and inhibiting complicance is not often recognized. Physicians accept the need for patient education but do not accept responsibility for the patient's compliance. The disease denial/rationalization syndrome is a useful label for emotional resistance to the treatment program. An important factor is the extent to which the physician seeks to ascertain compliance. Compliance-gaining strategies must be applied with tact and flexibility."} {"id": "PMID:1266709", "title": "Brain imaging.", "content": "Imaging with radionuclides should be used in a complementary fashion with other neuroradiologic techniques. It is useful in the early detection and evaluation of intracranial neoplasm, cerebrovascular accident and abscess, and in postsurgical follow-up. Cisternography yields useful information about the functional status of cerebrospinal fluid pathways. Computerized axial tomography is a new technique of great promise that produces a cross-sectional image of the brain.", "contents": "Brain imaging. Imaging with radionuclides should be used in a complementary fashion with other neuroradiologic techniques. It is useful in the early detection and evaluation of intracranial neoplasm, cerebrovascular accident and abscess, and in postsurgical follow-up. Cisternography yields useful information about the functional status of cerebrospinal fluid pathways. Computerized axial tomography is a new technique of great promise that produces a cross-sectional image of the brain."} {"id": "PMID:1266710", "title": "Editorial: Observations on the diagnosis of isolated rheumatic carditis.", "content": "There are many similarities between the clinical features of viral heart disease and of rheumatic carditis, as defined in the revised Jones criteria for the diagnosis of rheumatic fever. Because of this, it is likely that viral heart disease has been, and still is, diagnosed as rheumatic. This situation can be avoided if isolated rheumatic carditis is diagnosed only when a viral etiology has been definitely excluded, and when there is unequivocal evidence of recent infection with an appropriate strain of streptococcus.", "contents": "Editorial: Observations on the diagnosis of isolated rheumatic carditis. There are many similarities between the clinical features of viral heart disease and of rheumatic carditis, as defined in the revised Jones criteria for the diagnosis of rheumatic fever. Because of this, it is likely that viral heart disease has been, and still is, diagnosed as rheumatic. This situation can be avoided if isolated rheumatic carditis is diagnosed only when a viral etiology has been definitely excluded, and when there is unequivocal evidence of recent infection with an appropriate strain of streptococcus."} {"id": "PMID:1266711", "title": "Clinical correlates of coronary cineangiography in young males with myocardial infarction.", "content": "Thirty-eight men who suffered acute transmural myocardial infarction before age 40, and after recovery were New York Heart Association functional Class I or II, were studied by noninvasive means and by coronary angiography in order to determine whether these nonivasive studies could predict the presence of significant coronary artery disease remote from that felt to be responsible for the previous myocardial infarction. Patients were divided into two groups on the basis of the absence (Group I) or presence (Group II) of obstructive disease in a major coronary artery supplying myocardium remote from the prior myocardial infarction. There were 21 patients in Group I and 17 patients in Group II. They did not differ with respect to age, abnormalities of lipid or glucose metabolism, family history, history of hypertension or cigarette use, presence of obesity, or infarct localization. Ten of 17 patients in Group II had angina pectoris; only 3/21 patients in Group I had angina pectoris (p less than 0.01). All 12 patients tested in Group II had a positive maximal exercise tolerance test; only 1/17 patients tested in Group I was similarly positive (p less than 0.001). The absence of angina pectoris and the presence of a negative maximal exercise tolerance test is strong evidence against the pressure of significant CAD remote from that responsible for the prior myocardial infarction.", "contents": "Clinical correlates of coronary cineangiography in young males with myocardial infarction. Thirty-eight men who suffered acute transmural myocardial infarction before age 40, and after recovery were New York Heart Association functional Class I or II, were studied by noninvasive means and by coronary angiography in order to determine whether these nonivasive studies could predict the presence of significant coronary artery disease remote from that felt to be responsible for the previous myocardial infarction. Patients were divided into two groups on the basis of the absence (Group I) or presence (Group II) of obstructive disease in a major coronary artery supplying myocardium remote from the prior myocardial infarction. There were 21 patients in Group I and 17 patients in Group II. They did not differ with respect to age, abnormalities of lipid or glucose metabolism, family history, history of hypertension or cigarette use, presence of obesity, or infarct localization. Ten of 17 patients in Group II had angina pectoris; only 3/21 patients in Group I had angina pectoris (p less than 0.01). All 12 patients tested in Group II had a positive maximal exercise tolerance test; only 1/17 patients tested in Group I was similarly positive (p less than 0.001). The absence of angina pectoris and the presence of a negative maximal exercise tolerance test is strong evidence against the pressure of significant CAD remote from that responsible for the prior myocardial infarction."} {"id": "PMID:1266712", "title": "A combined electrophysiological and anatomical study of the human fetal heart.", "content": "Five human fetal hearts of gestational ages ranging from 12 to 16 weeks were studied with both electrophysiological and anatomical techniques. The electrophysiological behavior of these hearts was comparable with results obtained with other animal species and adult human hearts. This indicates that the fetal heart is functionally mature from an early stage of development; however the tissues are not fully differentiated from an anatomical standpoint. Results of mapping experiments indicated that atrial activation occurred through broad wave fronts, and no electrophysiological evidence was found to support the concept of \"specialized internodal conduction.\" In two hearts, the node and bundle were found to be anatomical contiguity with ventricular myocardium throughout their length, but the conducting tissues were already functionally insulated from the ventricles. The results have significance with regard to concepts of the \"sudden death in infancy syndrome\" and ventricular pre-excitation.", "contents": "A combined electrophysiological and anatomical study of the human fetal heart. Five human fetal hearts of gestational ages ranging from 12 to 16 weeks were studied with both electrophysiological and anatomical techniques. The electrophysiological behavior of these hearts was comparable with results obtained with other animal species and adult human hearts. This indicates that the fetal heart is functionally mature from an early stage of development; however the tissues are not fully differentiated from an anatomical standpoint. Results of mapping experiments indicated that atrial activation occurred through broad wave fronts, and no electrophysiological evidence was found to support the concept of \"specialized internodal conduction.\" In two hearts, the node and bundle were found to be anatomical contiguity with ventricular myocardium throughout their length, but the conducting tissues were already functionally insulated from the ventricles. The results have significance with regard to concepts of the \"sudden death in infancy syndrome\" and ventricular pre-excitation."} {"id": "PMID:1266713", "title": "Single right-sided precordial lead in the diagnosis of right ventricular involvement in inferior myocardial infarction.", "content": "The ST segment in a single right-sided chest lead, CR4R, has been studied in 92 consecutive patients with acute inferior transmural left ventricular myocardial infarction. A transient ST- segment rise of more than 1 mm. was recorded in 35 patients, and strongly indicated a significant extension of the infarction to the posterior free right ventricular wall according to autopsy findings. This ECG pattern was furthermore associated with right-sided heart failure, hypotension and oliguria. Left heart failure was also common. The short-term prognosis of patients with ST-segment elevation in CR4R was poor.", "contents": "Single right-sided precordial lead in the diagnosis of right ventricular involvement in inferior myocardial infarction. The ST segment in a single right-sided chest lead, CR4R, has been studied in 92 consecutive patients with acute inferior transmural left ventricular myocardial infarction. A transient ST- segment rise of more than 1 mm. was recorded in 35 patients, and strongly indicated a significant extension of the infarction to the posterior free right ventricular wall according to autopsy findings. This ECG pattern was furthermore associated with right-sided heart failure, hypotension and oliguria. Left heart failure was also common. The short-term prognosis of patients with ST-segment elevation in CR4R was poor."} {"id": "PMID:1266714", "title": "Relative insesitivity of isovolumic phase indices in the assessment of left ventricular function.", "content": "1. The authors compared the sensitivity of the isovolumic phase indices (contractility indices) against LV function curves (\"pump-function\" indices) in assessing ventricular performance. 2. Certain modifications of the usual isovolumic phase indices, especially those introducing the concept of comparison of exercise with rest, seemed to us to be slightly more helpful in separating normal subjects from the patient with coronary artery disease or cardiomyopathies, but these differences were not striking when statistically evaluated, and could not be utilized in assessment of left ventricular function in individual patients. 3. The construction of left ventricular function curves, in our hands, yielded equally as satisfactory information and, in addition, was much simpler to perform. 4. It is concluded that contractility indices are relatively insensitive in the assessment of left ventricular function, and that they offer little advantage over \"pump-function\" indices for this purpose.", "contents": "Relative insesitivity of isovolumic phase indices in the assessment of left ventricular function. 1. The authors compared the sensitivity of the isovolumic phase indices (contractility indices) against LV function curves (\"pump-function\" indices) in assessing ventricular performance. 2. Certain modifications of the usual isovolumic phase indices, especially those introducing the concept of comparison of exercise with rest, seemed to us to be slightly more helpful in separating normal subjects from the patient with coronary artery disease or cardiomyopathies, but these differences were not striking when statistically evaluated, and could not be utilized in assessment of left ventricular function in individual patients. 3. The construction of left ventricular function curves, in our hands, yielded equally as satisfactory information and, in addition, was much simpler to perform. 4. It is concluded that contractility indices are relatively insensitive in the assessment of left ventricular function, and that they offer little advantage over \"pump-function\" indices for this purpose."} {"id": "PMID:1266715", "title": "Korotkoff sound filtering for automated three-phase measurement of blood pressure.", "content": "Under rest conditions, changes in the Korotkoff sounds at phases I, IV, and V can be correlated with specific frequencies within the bandpass of the stethoscope. A filter capable of detecting the changes in Korotkoff sounds at phases I, IV, and V is described together with the frequency changes that characterize these phases. The importance of frequency components outside the bandpass of the stethoscope is stressed, especially in terms of the possibility of yielding more clinical information and, perhaps, additional clues above the origin of the Korotkoff sounds themselves.", "contents": "Korotkoff sound filtering for automated three-phase measurement of blood pressure. Under rest conditions, changes in the Korotkoff sounds at phases I, IV, and V can be correlated with specific frequencies within the bandpass of the stethoscope. A filter capable of detecting the changes in Korotkoff sounds at phases I, IV, and V is described together with the frequency changes that characterize these phases. The importance of frequency components outside the bandpass of the stethoscope is stressed, especially in terms of the possibility of yielding more clinical information and, perhaps, additional clues above the origin of the Korotkoff sounds themselves."} {"id": "PMID:1266716", "title": "Formation of coronary arterial thrombi in relation to onset of necrosis in acute myocardial infarction in man. A clinical and autoradiographic study.", "content": "The presence of radioactivity in coronary arterial thrombi was studied at necropsy by autoradiography in 12 patients with acute myocardial infarction. Seven patients had been given 125I-and five patients 131I-labeled fibrinogen. With a short interval (less than 10 hours) between onset of symptoms and injection of fibrinogen the entire thrombus was radioactive in four of five patients, whereas with longer time intervals only parts or none of the thrombus contained detectable radioactivity. The findings give further evidence that thrombus formation in acute myocardial infarction probably is a slow process and that the major part of the thrombus may form after the onset of necrosis.", "contents": "Formation of coronary arterial thrombi in relation to onset of necrosis in acute myocardial infarction in man. A clinical and autoradiographic study. The presence of radioactivity in coronary arterial thrombi was studied at necropsy by autoradiography in 12 patients with acute myocardial infarction. Seven patients had been given 125I-and five patients 131I-labeled fibrinogen. With a short interval (less than 10 hours) between onset of symptoms and injection of fibrinogen the entire thrombus was radioactive in four of five patients, whereas with longer time intervals only parts or none of the thrombus contained detectable radioactivity. The findings give further evidence that thrombus formation in acute myocardial infarction probably is a slow process and that the major part of the thrombus may form after the onset of necrosis."} {"id": "PMID:1266717", "title": "Ventricular performance measured during ejection: Studies in patients of the rate of change of ventricular power.", "content": "An expression indicative of the rate of change of ventricular power was derived and applied to the evaluation of left ventricular performance of patients with angina. Patients were categorized as having normal or abnormal ventricular performance on the basis of the ejection fraction, mean velocity of circumferential fiber shortening, and left ventricular end-diastolic volume index. In those with normal performance, the ejection rate of change of power was (25 +/- 2) times 108 dyne cm. sec. (-2); in patients with abnormal performance it was (11 +/- 1) times 10(8) dyne cm. sec. (-2) (P less than 0.001). There was no overlap of values between categories of patients. Such a clear distinction between categories was not seen with any of the commonly utilized isovolumic indices of performance. The rate of change of ventricular power measured during ejection is free of assumptions, yet has a fluid dynamic as well as a physiological meaning. It serves in an intergrative fashion by incorporating terms previously shown to be of functional significance. Previous studies in dogs showed that it reflected alterations of the inotropic state, yet it was relatively independent of alterations of preload or afterload. It appears, therefore, that it is an indicator of ventricular performance that has desirable characteristics.", "contents": "Ventricular performance measured during ejection: Studies in patients of the rate of change of ventricular power. An expression indicative of the rate of change of ventricular power was derived and applied to the evaluation of left ventricular performance of patients with angina. Patients were categorized as having normal or abnormal ventricular performance on the basis of the ejection fraction, mean velocity of circumferential fiber shortening, and left ventricular end-diastolic volume index. In those with normal performance, the ejection rate of change of power was (25 +/- 2) times 108 dyne cm. sec. (-2); in patients with abnormal performance it was (11 +/- 1) times 10(8) dyne cm. sec. (-2) (P less than 0.001). There was no overlap of values between categories of patients. Such a clear distinction between categories was not seen with any of the commonly utilized isovolumic indices of performance. The rate of change of ventricular power measured during ejection is free of assumptions, yet has a fluid dynamic as well as a physiological meaning. It serves in an intergrative fashion by incorporating terms previously shown to be of functional significance. Previous studies in dogs showed that it reflected alterations of the inotropic state, yet it was relatively independent of alterations of preload or afterload. It appears, therefore, that it is an indicator of ventricular performance that has desirable characteristics."} {"id": "PMID:1266718", "title": "Atrial T (Ta) loop in dogs with or without atrial injury.", "content": "In 46 dogs with experimentally produced complete A-V block, the P and the Ta waves before and after the atrial injury were recorded in scalar orthogonal ECG leads at high speed and high amplification. The P and the Ta loops were drawn by hand from the scalar ECG'S. In the dogs without atrial injury, the maximum Ta vector was oriented to the right, superiorly and anteriorly. The P-T angle was close to 180 degrees in each of the three planes. The magnitude of the maximum Ta vector was nearly proportionate to that of the maximum P vector in each plane. The Ta loop was a smooth, elongated ellipse in configuration and showed clockwise rotation in all planes, as did the P loop. The spatial atrial gradient obtained from the scalar ECG was small. In the dogs with atrial injury, the Ta loop changed in direction, configuration, and inscription direction. The P-Ta angle and the relative magnitude of the maximum Ta vector to that of the maximum P vector changed markedly. The change of the P loop remained minimum. The maximum Ta vector and spatial atrial gradient were oriented toward the atrial injury site. The magnitude of the spatial atrial gradient was extremely large after injury. These findings were thought to be important in suggesting the presence of atrial injury and its localization.", "contents": "Atrial T (Ta) loop in dogs with or without atrial injury. In 46 dogs with experimentally produced complete A-V block, the P and the Ta waves before and after the atrial injury were recorded in scalar orthogonal ECG leads at high speed and high amplification. The P and the Ta loops were drawn by hand from the scalar ECG'S. In the dogs without atrial injury, the maximum Ta vector was oriented to the right, superiorly and anteriorly. The P-T angle was close to 180 degrees in each of the three planes. The magnitude of the maximum Ta vector was nearly proportionate to that of the maximum P vector in each plane. The Ta loop was a smooth, elongated ellipse in configuration and showed clockwise rotation in all planes, as did the P loop. The spatial atrial gradient obtained from the scalar ECG was small. In the dogs with atrial injury, the Ta loop changed in direction, configuration, and inscription direction. The P-Ta angle and the relative magnitude of the maximum Ta vector to that of the maximum P vector changed markedly. The change of the P loop remained minimum. The maximum Ta vector and spatial atrial gradient were oriented toward the atrial injury site. The magnitude of the spatial atrial gradient was extremely large after injury. These findings were thought to be important in suggesting the presence of atrial injury and its localization."} {"id": "PMID:1266719", "title": "Percutaneous balloon atrial septostomy in infants with transposition of the great arteries.", "content": "Initial experience with PBAS in early management of neonate with TGA is described. Standard percutaneous techniques were used and modified by a series of dilations designed to introduce a septostomy catheter into the femoral vein. Thirty infants with TGA were catheterized, and PBAS was accomplished in 25. The mean aortic oxygen saturation rose from 55 to 72 per cent. Twenty-four infants were clinically palliated for at least 3 months; however, five required pre-elective surgery thought due to inadequate atrial mixing. No severe complications followed PBAS. Twenty-three patients underwent follow-up catheterization, in 17 through the vein used for PBAS. When compared to patients with TGA who had cutdown insertion of balloon septostomy catheters, the group treated by PBAS was similar in patient material, and successful septostomy. Those ballooned percutaneously had fewer complications and required slightly less time for the procedure. We feel that PBAS is a relatively easy and safe palliative procedure when performed in an infant with TGA. It should be considered by all those performing percutaneous diagnostic catheterization in infants and children.", "contents": "Percutaneous balloon atrial septostomy in infants with transposition of the great arteries. Initial experience with PBAS in early management of neonate with TGA is described. Standard percutaneous techniques were used and modified by a series of dilations designed to introduce a septostomy catheter into the femoral vein. Thirty infants with TGA were catheterized, and PBAS was accomplished in 25. The mean aortic oxygen saturation rose from 55 to 72 per cent. Twenty-four infants were clinically palliated for at least 3 months; however, five required pre-elective surgery thought due to inadequate atrial mixing. No severe complications followed PBAS. Twenty-three patients underwent follow-up catheterization, in 17 through the vein used for PBAS. When compared to patients with TGA who had cutdown insertion of balloon septostomy catheters, the group treated by PBAS was similar in patient material, and successful septostomy. Those ballooned percutaneously had fewer complications and required slightly less time for the procedure. We feel that PBAS is a relatively easy and safe palliative procedure when performed in an infant with TGA. It should be considered by all those performing percutaneous diagnostic catheterization in infants and children."} {"id": "PMID:1266721", "title": "Cannon waves with A-V association.", "content": "Under appropriate circumstances, cannon waves can occur in the presence of A-V associated rhythms. Presented here is a case of first degree A-V block with cannon waves. Recognition of these waves and their behavior aided in diagnosing the patient's rhythm. The cannon waves were documented by jugular venous pulse recordings.", "contents": "Cannon waves with A-V association. Under appropriate circumstances, cannon waves can occur in the presence of A-V associated rhythms. Presented here is a case of first degree A-V block with cannon waves. Recognition of these waves and their behavior aided in diagnosing the patient's rhythm. The cannon waves were documented by jugular venous pulse recordings."} {"id": "PMID:1266722", "title": "Remission and recovery from chronic, established, complete heart block.", "content": "The return of A-V conduction is described in a patient after two decades of high-grade or complete congenital heart block. Similar cases have been reported by others, with remission or even recovery commencing up to the fourth decade or later. A similar phenomenon is also described in four patients with acquired heart block of four to ten years' duration; in them, remission was usuallly brief but persisted for seven years in one patient. No full report of this seems to have been published previously. Possible explanations are discussed, but no conclusion is reached. Apart from its interest, the phenomenon is of importance with respect to the selection of demand-type electronic pacemakers in the management of patients with heart block.", "contents": "Remission and recovery from chronic, established, complete heart block. The return of A-V conduction is described in a patient after two decades of high-grade or complete congenital heart block. Similar cases have been reported by others, with remission or even recovery commencing up to the fourth decade or later. A similar phenomenon is also described in four patients with acquired heart block of four to ten years' duration; in them, remission was usuallly brief but persisted for seven years in one patient. No full report of this seems to have been published previously. Possible explanations are discussed, but no conclusion is reached. Apart from its interest, the phenomenon is of importance with respect to the selection of demand-type electronic pacemakers in the management of patients with heart block."} {"id": "PMID:1266723", "title": "Arterial thromboembolic complications in patients with Starr-Edwards aortic ball valve prostheses.", "content": "Aterial thromboembolic complications were studied in 253 patients who had a single aortic Starr-Edwards ball valve implanted. During the first postoperative month, six patients died from myocardial infarction, one was reoperated because of leakage caused by thrombus on the valve, and five others suffered six thromboembolic episodes. Forty-six late thromboembolic complications occurred in 40 of the 216 patients who survived the postoperative period. Seven died, four from cerebral emboli and three from myocardial infarction. The late incidence was 7 episodes per 100 patients per year. Valves of series 1200 carried a significantly higher risk of arterial thromboembolism than did those of series 2300, and most episodes occurred in patients with cell controlled anticoagulant treatment. The incidence was not influenced by time since operation, continuous arrhythmia, concomitant mitral valve disease, heart size, or the degree of intravascular hemolysis. It is concluded that arterial thromboembolic complications represent a major threat to patients with aortic ball valves even several years after operation and in spite of intense anticoagulant therapy.", "contents": "Arterial thromboembolic complications in patients with Starr-Edwards aortic ball valve prostheses. Aterial thromboembolic complications were studied in 253 patients who had a single aortic Starr-Edwards ball valve implanted. During the first postoperative month, six patients died from myocardial infarction, one was reoperated because of leakage caused by thrombus on the valve, and five others suffered six thromboembolic episodes. Forty-six late thromboembolic complications occurred in 40 of the 216 patients who survived the postoperative period. Seven died, four from cerebral emboli and three from myocardial infarction. The late incidence was 7 episodes per 100 patients per year. Valves of series 1200 carried a significantly higher risk of arterial thromboembolism than did those of series 2300, and most episodes occurred in patients with cell controlled anticoagulant treatment. The incidence was not influenced by time since operation, continuous arrhythmia, concomitant mitral valve disease, heart size, or the degree of intravascular hemolysis. It is concluded that arterial thromboembolic complications represent a major threat to patients with aortic ball valves even several years after operation and in spite of intense anticoagulant therapy."} {"id": "PMID:1266731", "title": "Effect of altitude on personal respirable dust sampler calibration.", "content": "Air sampling instruments often are used at altitudes other than the altitude at which they were calibrated. This investigation quantitates the effect of personal samplers and provides empirical relationships for adjusting the calibration mark for use at any altitude.", "contents": "Effect of altitude on personal respirable dust sampler calibration. Air sampling instruments often are used at altitudes other than the altitude at which they were calibrated. This investigation quantitates the effect of personal samplers and provides empirical relationships for adjusting the calibration mark for use at any altitude."} {"id": "PMID:1266732", "title": "User tests of ear defenders.", "content": "Ten different common muff-type ear defenders were tested by 50 potential users for comfort and ease of use. Results showed short-term (3 min) impressions to be a good predictor of long-term comfort; defenders were ranked for comfort and pointers are given for important design features. Only comfortable ear defenders will be worn properly.", "contents": "User tests of ear defenders. Ten different common muff-type ear defenders were tested by 50 potential users for comfort and ease of use. Results showed short-term (3 min) impressions to be a good predictor of long-term comfort; defenders were ranked for comfort and pointers are given for important design features. Only comfortable ear defenders will be worn properly."} {"id": "PMID:1266733", "title": "Experimental human exposures to tetrachloroethylene vapor and elimination in breath after inhalation.", "content": "Volunteers were exposed in a controlled environment chamber and concentrations of tetrachloroethylene in alveolar air were determined. Results show a proportional relationship between the level of exposure and the alveolar concentration curve. Accordingly, tetrachloroethylene breath decay curves can be used as a method to monitor time-weighted average exposures.", "contents": "Experimental human exposures to tetrachloroethylene vapor and elimination in breath after inhalation. Volunteers were exposed in a controlled environment chamber and concentrations of tetrachloroethylene in alveolar air were determined. Results show a proportional relationship between the level of exposure and the alveolar concentration curve. Accordingly, tetrachloroethylene breath decay curves can be used as a method to monitor time-weighted average exposures."} {"id": "PMID:1266734", "title": "An improved method for monitoring heat stress levels in the workplace.", "content": "Studies in 15 industries revealed characteristic empirical relationships between workplace environmental conditions and outside weather conditions. These relationships, expressed in the form of predictive models for Wet Bulb Globe Temperature, can be used to estimate WBGT from weather forecasts, weather reports, or current meterorological measurements.", "contents": "An improved method for monitoring heat stress levels in the workplace. Studies in 15 industries revealed characteristic empirical relationships between workplace environmental conditions and outside weather conditions. These relationships, expressed in the form of predictive models for Wet Bulb Globe Temperature, can be used to estimate WBGT from weather forecasts, weather reports, or current meterorological measurements."} {"id": "PMID:1266735", "title": "A simple gas chromatographic method for the analysis of trace organics in ambient air.", "content": "A simple method using adsorption, heat desorption, and F.I.D. gas chromatography to determine ppb quantities of various organic vapors in air is described. Laboratory results with chemicals such as bischloromethyl ether, vinyl chloride monomer and volatile ketones are discussed.", "contents": "A simple gas chromatographic method for the analysis of trace organics in ambient air. A simple method using adsorption, heat desorption, and F.I.D. gas chromatography to determine ppb quantities of various organic vapors in air is described. Laboratory results with chemicals such as bischloromethyl ether, vinyl chloride monomer and volatile ketones are discussed."} {"id": "PMID:1266736", "title": "Work scheduling under normal and prolonged-vibration environments.", "content": "This paper summarizes the research conducted to study human performance and recovery under prolonged, whole-body, vertical vibration. The results showed that performance under vibratory environment is inferior to that under normal environment. Interaction between work-rest schedules and the vibratory environment was detected. Parameters affecting selection of optimum work-rest schedules are discussed.", "contents": "Work scheduling under normal and prolonged-vibration environments. This paper summarizes the research conducted to study human performance and recovery under prolonged, whole-body, vertical vibration. The results showed that performance under vibratory environment is inferior to that under normal environment. Interaction between work-rest schedules and the vibratory environment was detected. Parameters affecting selection of optimum work-rest schedules are discussed."} {"id": "PMID:1266737", "title": "Elevated urinary phenol levels in beagle dogs treated with salol.", "content": "Dogs administered 500 or 250 mg of salol/kg/day showed transient toxicity of a reversible nature. Doses of 125 mg salol/kg/day caused no discernible ill effects in spite of urinary phenol levels elevated as high as 6144 ppm. It appears as if exposure to a compound other than benzene can cause an elevation of urinary phenol.", "contents": "Elevated urinary phenol levels in beagle dogs treated with salol. Dogs administered 500 or 250 mg of salol/kg/day showed transient toxicity of a reversible nature. Doses of 125 mg salol/kg/day caused no discernible ill effects in spite of urinary phenol levels elevated as high as 6144 ppm. It appears as if exposure to a compound other than benzene can cause an elevation of urinary phenol."} {"id": "PMID:1266738", "title": "Tris (2,3-dibromopropyl) phosphate: human contact sensitization.", "content": "Liquid TBP caused delayed hypersensitivity in human subject maximization tests. It showed a dose/response relationship and is judged a weak to mild sensitizer. Patch testing a pre-sensitized subjects using fabrics containing TBP produced responses varying with the availability of the agent at the fiber surface. It appears improbable that treated textiles affording low TBP availability will cause sensitization.", "contents": "Tris (2,3-dibromopropyl) phosphate: human contact sensitization. Liquid TBP caused delayed hypersensitivity in human subject maximization tests. It showed a dose/response relationship and is judged a weak to mild sensitizer. Patch testing a pre-sensitized subjects using fabrics containing TBP produced responses varying with the availability of the agent at the fiber surface. It appears improbable that treated textiles affording low TBP availability will cause sensitization."} {"id": "PMID:1266739", "title": "Correlation of echocardiographic and clinical findings in patients with pericardial effusion.", "content": "Clinical data and echocardiographic findings were correlated in 20 patients with pericardial effusion. Moderate to large effusions were associated with increased motion of the entire heart within the pericardial sac. A correlation was found between the estimated volume of fluid and the diastolic excursion and velocity of the right ventricular and left ventricular walls (P less than 0.01). For any given volume of fluid as estimated from the echocardiogram neoplastic effusions resulted in greater increments in wall motion (P less than 0.02). Patterns of \"pseudo\" mitral valve prolapse occurred and were correlated with the extent and timing of cardiac swinging and heart rate. A diminished E-F slope of the mitral valve echo and notch on the right ventricular epicardial echo during early systole were found in all four patients with pericardial tamponade. These preliminary observations suggest that echocardiographic examination of patients with pericardial effusion may provide clues to the presence or absence of tamponade in addition to providing an estimate of the quantity of fluid in the pericardial sac.", "contents": "Correlation of echocardiographic and clinical findings in patients with pericardial effusion. Clinical data and echocardiographic findings were correlated in 20 patients with pericardial effusion. Moderate to large effusions were associated with increased motion of the entire heart within the pericardial sac. A correlation was found between the estimated volume of fluid and the diastolic excursion and velocity of the right ventricular and left ventricular walls (P less than 0.01). For any given volume of fluid as estimated from the echocardiogram neoplastic effusions resulted in greater increments in wall motion (P less than 0.02). Patterns of \"pseudo\" mitral valve prolapse occurred and were correlated with the extent and timing of cardiac swinging and heart rate. A diminished E-F slope of the mitral valve echo and notch on the right ventricular epicardial echo during early systole were found in all four patients with pericardial tamponade. These preliminary observations suggest that echocardiographic examination of patients with pericardial effusion may provide clues to the presence or absence of tamponade in addition to providing an estimate of the quantity of fluid in the pericardial sac."} {"id": "PMID:1266740", "title": "Subdivided left atrium: an expanded concept of cor triatriatum sinistrum.", "content": "Twenty-four hearts with cor triatriatum were studied. On the basis of this material and a review of the literature a new classification of \"subdivided left atrium\" is proposed. Tye A, the most common form of subdivided left atrium, is the classic cor triatriatum with its multiple variations of partial anomalous pulmonary venous drainage; the fossa ovalis can be related to the proximal left atrial chamber (type A, a) or the distal left atrial chamber (type A, b). Type B hearts are related to (but not identical with) total anomalous pulmonary venous drainage into the coronary sinus; the coronary sinus opening is atretic in these hearts; abnormal defects connect the proximal left atrial chamber usually with the right atrium only, rarely also with the distal left atrial chamber. The Type C heart, first reported in this paper, has a superiorly and medially situated proximal chamber, located between the right and distal left atrium; it does not receive any pulmonary veins; the coronary sinus is normally formed. Current morphogenetic hypotheses that satisfactorily explain the Type A b and B heart fail to account for the Type A a and C heart.", "contents": "Subdivided left atrium: an expanded concept of cor triatriatum sinistrum. Twenty-four hearts with cor triatriatum were studied. On the basis of this material and a review of the literature a new classification of \"subdivided left atrium\" is proposed. Tye A, the most common form of subdivided left atrium, is the classic cor triatriatum with its multiple variations of partial anomalous pulmonary venous drainage; the fossa ovalis can be related to the proximal left atrial chamber (type A, a) or the distal left atrial chamber (type A, b). Type B hearts are related to (but not identical with) total anomalous pulmonary venous drainage into the coronary sinus; the coronary sinus opening is atretic in these hearts; abnormal defects connect the proximal left atrial chamber usually with the right atrium only, rarely also with the distal left atrial chamber. The Type C heart, first reported in this paper, has a superiorly and medially situated proximal chamber, located between the right and distal left atrium; it does not receive any pulmonary veins; the coronary sinus is normally formed. Current morphogenetic hypotheses that satisfactorily explain the Type A b and B heart fail to account for the Type A a and C heart."} {"id": "PMID:1266741", "title": "Aortic valve atresia: a new classification based on necropsy study of 73 cases.", "content": "Certain clinical and morphologic observations are described in 73 necropsy patients with aortic valve atresia. The mean age at death was 5 days; 80 percent died during the first week of life, and 70 percent were boys. Of the 73 patients, 69 (95 percent) had a hypoplastic left ventricle with intact ventricular septum and either an atretic (25 patients) or hypoplastic (44 patients) mitral valve. The other four patients had a well developed left ventricle with one or more defects in the ventricular septum and either an atretic (one patient) or well developed (three patients) mitral valve. Review of previous reports on aortic valve atresia disclosed that a well developed left ventricle or ventricular septal defect in association with absence of the aortic valve was extremely rare. A new classification for aortic valve atresia is presented based on the status of the ventricular septum, which in turn appears to determine the size of the left ventricular cavity. The predilection for male subjects for all types of aortic valve disease, including atresia, is emphasized.", "contents": "Aortic valve atresia: a new classification based on necropsy study of 73 cases. Certain clinical and morphologic observations are described in 73 necropsy patients with aortic valve atresia. The mean age at death was 5 days; 80 percent died during the first week of life, and 70 percent were boys. Of the 73 patients, 69 (95 percent) had a hypoplastic left ventricle with intact ventricular septum and either an atretic (25 patients) or hypoplastic (44 patients) mitral valve. The other four patients had a well developed left ventricle with one or more defects in the ventricular septum and either an atretic (one patient) or well developed (three patients) mitral valve. Review of previous reports on aortic valve atresia disclosed that a well developed left ventricle or ventricular septal defect in association with absence of the aortic valve was extremely rare. A new classification for aortic valve atresia is presented based on the status of the ventricular septum, which in turn appears to determine the size of the left ventricular cavity. The predilection for male subjects for all types of aortic valve disease, including atresia, is emphasized."} {"id": "PMID:1266742", "title": "Congenital valvular aortic stenosis: clinical detection of small pressure gradient. Prepared for the joint study on the joint study on the natural history of congenital heart defects.", "content": "Clinical variables (from the history, physical examination, electrocardiogram and chest radiograph) were related to the pressure gradient measured between the left ventricle and the aorta in 434 young patients with congenital valvular aortic stenosis admitted to a national collaborative study. The aim was to devise a composite clinical criterion for the recognition of patients with a small pressure gradient, so as to expand the opportunity for avoiding cardiac catheterization in such patients. Flattened or inverted T waves in lead V6 were found to be inconsistent with mild disease. Therefore, a composite criterion, providing an estimate of pressure gradient, was developed for patients without T wave changes. The final criterion, based on multivariate analysis, involved only the intensity of the systolic murmor, the presence or absence of an early diastolic murmur, and voltages of the Q and R waves in lead V6. Patients with a low estimate by this procedure rarely had a large measured gradient. Only 3.7 percent (6 of 161) with an estimated gradient of less than 45 mm Hg had a gradient at cardiac catheterization of 80 or more mm Hg; none (0 of 32) with an estimated gradient of less than 30 mm Hg had a gradient of 50 or more mm Hg. This criterion should be helpful in avoiding unnecessary catheterization by identifying some patients with valvular aortic stenosis who have a small pressure gradient.", "contents": "Congenital valvular aortic stenosis: clinical detection of small pressure gradient. Prepared for the joint study on the joint study on the natural history of congenital heart defects. Clinical variables (from the history, physical examination, electrocardiogram and chest radiograph) were related to the pressure gradient measured between the left ventricle and the aorta in 434 young patients with congenital valvular aortic stenosis admitted to a national collaborative study. The aim was to devise a composite clinical criterion for the recognition of patients with a small pressure gradient, so as to expand the opportunity for avoiding cardiac catheterization in such patients. Flattened or inverted T waves in lead V6 were found to be inconsistent with mild disease. Therefore, a composite criterion, providing an estimate of pressure gradient, was developed for patients without T wave changes. The final criterion, based on multivariate analysis, involved only the intensity of the systolic murmor, the presence or absence of an early diastolic murmur, and voltages of the Q and R waves in lead V6. Patients with a low estimate by this procedure rarely had a large measured gradient. Only 3.7 percent (6 of 161) with an estimated gradient of less than 45 mm Hg had a gradient at cardiac catheterization of 80 or more mm Hg; none (0 of 32) with an estimated gradient of less than 30 mm Hg had a gradient of 50 or more mm Hg. This criterion should be helpful in avoiding unnecessary catheterization by identifying some patients with valvular aortic stenosis who have a small pressure gradient."} {"id": "PMID:1266743", "title": "The palliative Mustard operation: rationale and results.", "content": "The tendency toward development of severe pulmonary vascular obstructive disease in patients with complete transposition of the great arteries and associated large ventricular septal defect has been well documented. The physiologic consequence of this process is a significant reduction in intercirculatory mixing, resulting in increasingly severe levels of systemic arterial hypoxemia, compensatory polycythemia and an associated significant increase in symptoms. Data indicate that definitive surgical correction in patients with pulmonary arteriolar resistance of more than 10.0 units m2 is associated with a prohibitive operative mortality. However, the \"palliative\" Mustard operation (that is, intraatrial baffle repair, leaving the ventricular septal defect open) can be accomplished with relatively low risk and substantial hemodynamic benefits to the patient. It is erroneous to assume that the result of the operation will be a mere \"reversal\" of the preoperative systemic arterial and pulmonary arterial saturations, as shown by a review of the hemodynamic changes attributable to the operation. After the operation, systemic arterial saturations of 80 to 93 percent have been achieved, with a concomitant significant reduction in hemoglobin concentration, to a near normal level in some. Although the long-term prognosis in such patients is unknown, the reduction in symptoms and increase in exercise tolerance soon after operation are most gratifying.", "contents": "The palliative Mustard operation: rationale and results. The tendency toward development of severe pulmonary vascular obstructive disease in patients with complete transposition of the great arteries and associated large ventricular septal defect has been well documented. The physiologic consequence of this process is a significant reduction in intercirculatory mixing, resulting in increasingly severe levels of systemic arterial hypoxemia, compensatory polycythemia and an associated significant increase in symptoms. Data indicate that definitive surgical correction in patients with pulmonary arteriolar resistance of more than 10.0 units m2 is associated with a prohibitive operative mortality. However, the \"palliative\" Mustard operation (that is, intraatrial baffle repair, leaving the ventricular septal defect open) can be accomplished with relatively low risk and substantial hemodynamic benefits to the patient. It is erroneous to assume that the result of the operation will be a mere \"reversal\" of the preoperative systemic arterial and pulmonary arterial saturations, as shown by a review of the hemodynamic changes attributable to the operation. After the operation, systemic arterial saturations of 80 to 93 percent have been achieved, with a concomitant significant reduction in hemoglobin concentration, to a near normal level in some. Although the long-term prognosis in such patients is unknown, the reduction in symptoms and increase in exercise tolerance soon after operation are most gratifying."} {"id": "PMID:1266744", "title": "Residual hypertension after coarctectomy in children.", "content": "Coarctectomy in 190 children aged over 1 year to 15 years at operation produced a significant reduction in blood pressure for the group as a whole. Forty-nine patients (24 percent) remained hypertensive. Postoperative hypertension was unexplained in 29 (15 percent) of the 190 patients, and coarctation persisted or recurred in 20 (11 percent). For patients operated on between the ages of 4 and 15 years the earlier the age of operation, the greater the reduction in the blood pressure index: (measured blood pressure/normal mean systolic [or diastolic] blood pressure for age) X 100.", "contents": "Residual hypertension after coarctectomy in children. Coarctectomy in 190 children aged over 1 year to 15 years at operation produced a significant reduction in blood pressure for the group as a whole. Forty-nine patients (24 percent) remained hypertensive. Postoperative hypertension was unexplained in 29 (15 percent) of the 190 patients, and coarctation persisted or recurred in 20 (11 percent). For patients operated on between the ages of 4 and 15 years the earlier the age of operation, the greater the reduction in the blood pressure index: (measured blood pressure/normal mean systolic [or diastolic] blood pressure for age) X 100."} {"id": "PMID:1266745", "title": "Role of echocardiography in patients with coronary artery disease.", "content": "Impaired left ventricular performance, one of the hallmarks of coronary artery disease, can be detected by echocardiography in various ways. One of these approaches is the recording of abnormal wall motion. Because of the way in which the left ventricle can be examined echocardiographically, this technique has the capability of detecting regional wall abnormalities. In fact echocardiography is probably the most sensitive technique available, including even contrast ventriculography, for the detection of akinetic, hypokinetic or dyskinetic wall segments. With increasing experience it is apparent that more areas of the left ventricle can be examined echocardiographically than had previously been thought possible. Newer techniques include directing the ultrasonic beam not only through the body of the left ventricle but also toward the apical portion of the ventricle near the vicinity of the papillary muscles. In addition the true anterior left ventricular wall can be examined by moving the transducer laterally away from the left sternal border. Yet another approach utilizes a subxiphoid position for the transducer while the ultrasonic beam is directed through the medial portion of the septum and posterolateral wall of the left ventricle. M-mode scanning techniques together with recently developed cross-sectional echocardiographic instruments give great promise of improved detection of abnormalities of ventricular shape, especially the presence of aneurysms. The cross-sectional approach makes it possible to examine the left ventricular apex, an area virtually impossible to record with M-mode echocardiography. Recording of left ventricular dimensions and abnormal mitral valve motion may help in assessing overall left ventricular performance. A dilated left ventricular dimension in the vicinity of the mitral valve seems to be an ominous finding both in patients with acute myocardial infarction and in patients with chronic coronary disease being considered for possible surgery. Another echocardiographic sign of abnormal ventricular performance is altered closure of the mitral valve, which reflects a significantly elevated left ventricular diastolic pressure. These echocardiographic techniques are still in the investigational stages and are more technically difficult than the usual echocardiographic applications. However, the preliminary data are encouraging and make us hopeful that echocardiography will prove to be an important tool in the overall evaluation of the left ventricle in patients with coronary artery disease.", "contents": "Role of echocardiography in patients with coronary artery disease. Impaired left ventricular performance, one of the hallmarks of coronary artery disease, can be detected by echocardiography in various ways. One of these approaches is the recording of abnormal wall motion. Because of the way in which the left ventricle can be examined echocardiographically, this technique has the capability of detecting regional wall abnormalities. In fact echocardiography is probably the most sensitive technique available, including even contrast ventriculography, for the detection of akinetic, hypokinetic or dyskinetic wall segments. With increasing experience it is apparent that more areas of the left ventricle can be examined echocardiographically than had previously been thought possible. Newer techniques include directing the ultrasonic beam not only through the body of the left ventricle but also toward the apical portion of the ventricle near the vicinity of the papillary muscles. In addition the true anterior left ventricular wall can be examined by moving the transducer laterally away from the left sternal border. Yet another approach utilizes a subxiphoid position for the transducer while the ultrasonic beam is directed through the medial portion of the septum and posterolateral wall of the left ventricle. M-mode scanning techniques together with recently developed cross-sectional echocardiographic instruments give great promise of improved detection of abnormalities of ventricular shape, especially the presence of aneurysms. The cross-sectional approach makes it possible to examine the left ventricular apex, an area virtually impossible to record with M-mode echocardiography. Recording of left ventricular dimensions and abnormal mitral valve motion may help in assessing overall left ventricular performance. A dilated left ventricular dimension in the vicinity of the mitral valve seems to be an ominous finding both in patients with acute myocardial infarction and in patients with chronic coronary disease being considered for possible surgery. Another echocardiographic sign of abnormal ventricular performance is altered closure of the mitral valve, which reflects a significantly elevated left ventricular diastolic pressure. These echocardiographic techniques are still in the investigational stages and are more technically difficult than the usual echocardiographic applications. However, the preliminary data are encouraging and make us hopeful that echocardiography will prove to be an important tool in the overall evaluation of the left ventricle in patients with coronary artery disease."} {"id": "PMID:1266747", "title": "Auscultatory perception of the fourth heart sound: effects of interval form fourth to first sound (S4-S1) and aging.", "content": "A clinically heterogeneous group of 48 subjects (aged 19 to 76 years) were searched for a fourth heart sound (S4) by three independent \"blind\" auscultators. Phonocardiograms recorded immediately after auscultation were measured by another \"blind\" observer. An S4 was identified in 32 subjects (67 per cent) in phonocardiograms with nominal filter peaks of both 70 and 35 hertz. Results in these subjects revealed two groups by auscultatory performance: those with an \"easily heard\" and those with an \"easily missed\" S4. Subjects with an \"easily missed\" S4 were significantly younger than those with an \"easily heard\" S4 (31.2 +/- 2.8 years versus 50.0 +/- 4.0 years, P less than 0.001). P-R and P-S4 intervals and relative amplitude of S4 (ratio of fourth to first heart sound [S1] amplitude) were not significantly different in the two groups. Splitting of the first heart sound (S1) was observed more frequently in the phonocardiogram of patients with an \"easily missed\" S4, but this trend did not reach statistical significance. The interval between S4 and the low frequency component of S1 was significantly short in those with an \"easily heard\" S4 (49.4 +/- 4.1 msec versus 70.0 +/- 5.0 msec, P less than 0.005). The mean S4-S1 (low frequency component) interval for the group with an \"easily heard\" S4 approximated 1 cycle length for S4 vibrations, a finding consistent with temporal acoustic summation. An alternate hypothesis is modification of S1.", "contents": "Auscultatory perception of the fourth heart sound: effects of interval form fourth to first sound (S4-S1) and aging. A clinically heterogeneous group of 48 subjects (aged 19 to 76 years) were searched for a fourth heart sound (S4) by three independent \"blind\" auscultators. Phonocardiograms recorded immediately after auscultation were measured by another \"blind\" observer. An S4 was identified in 32 subjects (67 per cent) in phonocardiograms with nominal filter peaks of both 70 and 35 hertz. Results in these subjects revealed two groups by auscultatory performance: those with an \"easily heard\" and those with an \"easily missed\" S4. Subjects with an \"easily missed\" S4 were significantly younger than those with an \"easily heard\" S4 (31.2 +/- 2.8 years versus 50.0 +/- 4.0 years, P less than 0.001). P-R and P-S4 intervals and relative amplitude of S4 (ratio of fourth to first heart sound [S1] amplitude) were not significantly different in the two groups. Splitting of the first heart sound (S1) was observed more frequently in the phonocardiogram of patients with an \"easily missed\" S4, but this trend did not reach statistical significance. The interval between S4 and the low frequency component of S1 was significantly short in those with an \"easily heard\" S4 (49.4 +/- 4.1 msec versus 70.0 +/- 5.0 msec, P less than 0.005). The mean S4-S1 (low frequency component) interval for the group with an \"easily heard\" S4 approximated 1 cycle length for S4 vibrations, a finding consistent with temporal acoustic summation. An alternate hypothesis is modification of S1."} {"id": "PMID:1266748", "title": "Clinical and arteriographic features of Prinzmetal's variant angina: documentation of etiologic factors.", "content": "Coronary arteriography performed in 17 patients with Prinzmetal's variant angina demonstrated high grade fixed obstructions in 9 patients (Group I) and insignificant or no fixed lesions in 8 patients (Group II). Group I consisted mostly of middle-aged or elderly men with S-T segment elevations in various sites; Group II included five younger women with S-T segment elevations in inferior electrocardiographic leads. In Group I patients, arteriography revealed a discrete high grade lesion located proximally in a major coronary artery in four patients and multivessel involvement in five patients. In Group II patients, spontaneous spasm was documented in three patients and spasm was pharmacologically provoked in two others during arteriography. The current study indicates that spasm is the responsible pathogenetic mechanism of myocardial ischemia in some patients with Prinzmetal angina and that this mechanism may be suspected from the clinical characteristics of these patients.", "contents": "Clinical and arteriographic features of Prinzmetal's variant angina: documentation of etiologic factors. Coronary arteriography performed in 17 patients with Prinzmetal's variant angina demonstrated high grade fixed obstructions in 9 patients (Group I) and insignificant or no fixed lesions in 8 patients (Group II). Group I consisted mostly of middle-aged or elderly men with S-T segment elevations in various sites; Group II included five younger women with S-T segment elevations in inferior electrocardiographic leads. In Group I patients, arteriography revealed a discrete high grade lesion located proximally in a major coronary artery in four patients and multivessel involvement in five patients. In Group II patients, spontaneous spasm was documented in three patients and spasm was pharmacologically provoked in two others during arteriography. The current study indicates that spasm is the responsible pathogenetic mechanism of myocardial ischemia in some patients with Prinzmetal angina and that this mechanism may be suspected from the clinical characteristics of these patients."} {"id": "PMID:1266749", "title": "Interventricular septal motion during preexcitation and normal conduction in Wolff-Parkinson-White syndrome: echocardiographic and electrophysiologic correlation.", "content": "Interventricular septal motion was studied by echocardiogram in 20 consecutive patients with documented Wolff-Parkinson-White (WPW) syndrome before and during electrophysiologic evaluation using His bundle recordings and pacing techniques. Characteristic abnormal interventricular septal motion was seen in 8 of 11 patients with type B WPW syndrome (groups I and II). All eight patients had electrocardiographic patterns consistent with an anomalous pathway located in the anterior right ventricular wall (group I). In five of these eight patients normalization of the QRS complex for one or more beats was accomplished and produced normalization of the septal motion in four; whereas in the fifth patient, who had an underlying atrial septal defect, the abnormal septal motion remained abnormal. All nine patients with type A WPW syndrome (groups III to V) had normal septal motion both during total preexcitation and during normalization of the QRS complex. The normalization of the abnormal interventricular septal motion with normalization of the QRS complex in type B WPW syndrome strongly suggests that the abnormal motion is related to an abnormal sequence of ventricular depolarization during preexcitation. Furthermore, persistent abnormal septal motion after normalization of the QRS complex suggests that other factors such as right ventricular volume overload may be responsible. Likewise, when abnormal septal motion occurs in the presence of type A WPW syndrome, an explanation other than preexcitation must be sought.", "contents": "Interventricular septal motion during preexcitation and normal conduction in Wolff-Parkinson-White syndrome: echocardiographic and electrophysiologic correlation. Interventricular septal motion was studied by echocardiogram in 20 consecutive patients with documented Wolff-Parkinson-White (WPW) syndrome before and during electrophysiologic evaluation using His bundle recordings and pacing techniques. Characteristic abnormal interventricular septal motion was seen in 8 of 11 patients with type B WPW syndrome (groups I and II). All eight patients had electrocardiographic patterns consistent with an anomalous pathway located in the anterior right ventricular wall (group I). In five of these eight patients normalization of the QRS complex for one or more beats was accomplished and produced normalization of the septal motion in four; whereas in the fifth patient, who had an underlying atrial septal defect, the abnormal septal motion remained abnormal. All nine patients with type A WPW syndrome (groups III to V) had normal septal motion both during total preexcitation and during normalization of the QRS complex. The normalization of the abnormal interventricular septal motion with normalization of the QRS complex in type B WPW syndrome strongly suggests that the abnormal motion is related to an abnormal sequence of ventricular depolarization during preexcitation. Furthermore, persistent abnormal septal motion after normalization of the QRS complex suggests that other factors such as right ventricular volume overload may be responsible. Likewise, when abnormal septal motion occurs in the presence of type A WPW syndrome, an explanation other than preexcitation must be sought."} {"id": "PMID:1266750", "title": "Experimental myocardial infarction: XII. Dynamic changes in segmental mechanical behavior of infarcted and non-infarcted myocardium.", "content": "The mechanical behavior of ischemic myocardium was studied in anesthetized open chest dogs. In each animal, a small well localized myocardial infarction was produced by ligation of a single ventricular branch of the left circumflex coronary artery. Serial in situ measurements of segment length were made by mercury-in-Silastic gauges sutured directly to the left ventricular surface. After coronary ligation, systolic aneurysmal bulging of the ischemic segment was uniformly noted. This was quantified as follows: normalized segment length change in this region, expressed in muscle lengths (where muscle lengths = phasic segment length amplitude/end-diastolic segment length), immediately increased from 0.06 +/- 0.01 (standard error of the mean) to 0.10 +/- 0.02 muscle lengths (+67 percent, P less than 0.02). Over a 6 hour period, muscle lengths progressively declined to near control values, but retained an aneurysmal contour. End-diastolic segment length increased 5 percent above control values after coronary occlusion and remained fixed at this level for 6 hours. In contrast, noninfarcted myocardium exhibited no significant changes in muscle length or end-diastolic segment length. These studies demonstrate that the degree of systolic aneurysmal bulging in infarcted myocardium, although initially great, resolves within 6 hours but retains an aneurysmal contour. These findings are consistent with either partial return of contractility or diminished local compliance, but persistence of an aneurysmal shape favors the latter mechanism. The fixed increase in end-diastolic segment length suggests that \"stress-relaxation\" takes place in the infarcted region. It is possible that diminished compliance in zones of infarction, previously noted after several days, begins within a few hours after the onset of ischemia.", "contents": "Experimental myocardial infarction: XII. Dynamic changes in segmental mechanical behavior of infarcted and non-infarcted myocardium. The mechanical behavior of ischemic myocardium was studied in anesthetized open chest dogs. In each animal, a small well localized myocardial infarction was produced by ligation of a single ventricular branch of the left circumflex coronary artery. Serial in situ measurements of segment length were made by mercury-in-Silastic gauges sutured directly to the left ventricular surface. After coronary ligation, systolic aneurysmal bulging of the ischemic segment was uniformly noted. This was quantified as follows: normalized segment length change in this region, expressed in muscle lengths (where muscle lengths = phasic segment length amplitude/end-diastolic segment length), immediately increased from 0.06 +/- 0.01 (standard error of the mean) to 0.10 +/- 0.02 muscle lengths (+67 percent, P less than 0.02). Over a 6 hour period, muscle lengths progressively declined to near control values, but retained an aneurysmal contour. End-diastolic segment length increased 5 percent above control values after coronary occlusion and remained fixed at this level for 6 hours. In contrast, noninfarcted myocardium exhibited no significant changes in muscle length or end-diastolic segment length. These studies demonstrate that the degree of systolic aneurysmal bulging in infarcted myocardium, although initially great, resolves within 6 hours but retains an aneurysmal contour. These findings are consistent with either partial return of contractility or diminished local compliance, but persistence of an aneurysmal shape favors the latter mechanism. The fixed increase in end-diastolic segment length suggests that \"stress-relaxation\" takes place in the infarcted region. It is possible that diminished compliance in zones of infarction, previously noted after several days, begins within a few hours after the onset of ischemia."} {"id": "PMID:1266751", "title": "Beneficial effect of lidocaine on ventricular electrical stability and spontaneous ventricular fibrillation during experimental myocardial infarction.", "content": "Several studies have questioned the efficacy of lidocaine in reducing the incidence of ventricular fibrillation shortly after acute myocardial infarction when arrhythmogenic mechanisms may be different from those operative several hours later. To determine whether lidocaine inhibits the occurrence of early ventricular fibrillation, the left anterior descending and septal coronary arteries were occluded at their origins in open chest anesthetized dogs. Fourteen of 16 control dogs died with ventricular fibrillation. Fifteen dogs received two different dose regimens of lidocaine before coronary occlusion. Of the 11 treated dogs maintaining lidocaine bl), 6 survived (P less than 0.05). Five dogs received the larger dose; all died, four having blood levels of 6.3 mug/ml or greater at the time of death. Ventricular fibrillation threshold also increased in six of eight dogs when lidocaine was administered after coronary occlusion. It is concluded that lidocaine at blood levels of 1.2 to 5.5 mug/ml significantly reduces the incidence of ventricular fibrillation early after coronary occlusion. Administration of this agent therefore may be of particular value in the early phase of acute myocardial infarction.", "contents": "Beneficial effect of lidocaine on ventricular electrical stability and spontaneous ventricular fibrillation during experimental myocardial infarction. Several studies have questioned the efficacy of lidocaine in reducing the incidence of ventricular fibrillation shortly after acute myocardial infarction when arrhythmogenic mechanisms may be different from those operative several hours later. To determine whether lidocaine inhibits the occurrence of early ventricular fibrillation, the left anterior descending and septal coronary arteries were occluded at their origins in open chest anesthetized dogs. Fourteen of 16 control dogs died with ventricular fibrillation. Fifteen dogs received two different dose regimens of lidocaine before coronary occlusion. Of the 11 treated dogs maintaining lidocaine bl), 6 survived (P less than 0.05). Five dogs received the larger dose; all died, four having blood levels of 6.3 mug/ml or greater at the time of death. Ventricular fibrillation threshold also increased in six of eight dogs when lidocaine was administered after coronary occlusion. It is concluded that lidocaine at blood levels of 1.2 to 5.5 mug/ml significantly reduces the incidence of ventricular fibrillation early after coronary occlusion. Administration of this agent therefore may be of particular value in the early phase of acute myocardial infarction."} {"id": "PMID:1266752", "title": "Combined hemodynamic-ultrasonic method for studying left ventricular wall stress: comparison with angiography.", "content": "Calculation of left ventricular wall stress in man has traditionally required angiographic and left ventricular pressure measurement, making study of interventions difficult. We have developed a combined hemodynamic-ultrasonic technique for measuring left ventricular meridional wass stress (sigma m) throughout the cardiac cycle. Simultaneous measurements of left ventricular pressure, ultrasonically determined wall thickness (h[echo]), and minor axis (D[echol]) were made during cardiac catheterization in nine subjects, three with chronic left ventricular pressure overload, four with left ventricular volume overload and two with normal left ventricular function. Within 30 minutes, left ventricular cineangiography was performed in each subject and angiographic wall thickness (h[angio]) and minor axis (D[angio]) were measured. Comparison of values for each subject throughout the cardiac cycle (average 18 data points/cycle) yielded close correlation: For D(echo) versus D(angio), r values ranged from 0.82 to 0.98 whereas for h(echo) versus h(angio), r values ranged from 0.56 to 0.98 for the nine subjects. Meridional wall stress was calculated after the method of Sandler and Dodge as PRi2/h(2Ri + h), where Ri equals the inner wall radius, calculated as D/2 for both ultrasonic and angiographic methods. Agreement between ultrasonic and angiographic methods was excellent in each subject, with close superimposition of the stress-time plots constructed by the different techniques. In summary, a new method for measurement of left ventricular wall stress has been developed and validated by comparison with an angiographic reference standard. This method has potential advantages, including the ability to study meridional wall stress continuously and to assess its response to serial interventions.", "contents": "Combined hemodynamic-ultrasonic method for studying left ventricular wall stress: comparison with angiography. Calculation of left ventricular wall stress in man has traditionally required angiographic and left ventricular pressure measurement, making study of interventions difficult. We have developed a combined hemodynamic-ultrasonic technique for measuring left ventricular meridional wass stress (sigma m) throughout the cardiac cycle. Simultaneous measurements of left ventricular pressure, ultrasonically determined wall thickness (h[echo]), and minor axis (D[echol]) were made during cardiac catheterization in nine subjects, three with chronic left ventricular pressure overload, four with left ventricular volume overload and two with normal left ventricular function. Within 30 minutes, left ventricular cineangiography was performed in each subject and angiographic wall thickness (h[angio]) and minor axis (D[angio]) were measured. Comparison of values for each subject throughout the cardiac cycle (average 18 data points/cycle) yielded close correlation: For D(echo) versus D(angio), r values ranged from 0.82 to 0.98 whereas for h(echo) versus h(angio), r values ranged from 0.56 to 0.98 for the nine subjects. Meridional wall stress was calculated after the method of Sandler and Dodge as PRi2/h(2Ri + h), where Ri equals the inner wall radius, calculated as D/2 for both ultrasonic and angiographic methods. Agreement between ultrasonic and angiographic methods was excellent in each subject, with close superimposition of the stress-time plots constructed by the different techniques. In summary, a new method for measurement of left ventricular wall stress has been developed and validated by comparison with an angiographic reference standard. This method has potential advantages, including the ability to study meridional wall stress continuously and to assess its response to serial interventions."} {"id": "PMID:1266753", "title": "Force-velocity-length relations in man expressed by a single hemodynamic expression: the ejection rate of change of power at peak tension.", "content": "An attempt was made to develop a hemodynamic indicator of pump function that relates to the contractile characteristics of cardiac muscle. The ejection rate of change of power has ideal characteristics for this purpose. It is firmly based upon theories of fluid dynamics and its derivation is free of assumptions related to heart structure and function. It is measured as p dQ/dt + Q dp/dt, where p = pressure and Q = flow. When measured at peak tension, the ejection rate of change of power was (12.3 +/- 0.8) X 10(8) dynes cm sec-2 in 11 patients with abnormal ventricular performance (P less than 0.001). Studies in dogs showed no effect of preload or afterload. This suggests a relation to characteristics of muscle fibers, which was shown. If one assumes a thin wall sphere, the ejection rate of change of power at peak tension reduces to the following function of tension (T), fiber length (2 pi r), and rate of shortening (2 pi dr/dt): d(power)/dt = 8 pi T](dr/dt)2 + r d2r/dt2[. Thus, the contractile characteristics of muscle fibers (force, velocity and tension) are related in an uncomplicated fashion by a single and highly discriminating hemodynamic indicator of ventricular performance, the ejection rate of change of ventricular power measured at peak tension.", "contents": "Force-velocity-length relations in man expressed by a single hemodynamic expression: the ejection rate of change of power at peak tension. An attempt was made to develop a hemodynamic indicator of pump function that relates to the contractile characteristics of cardiac muscle. The ejection rate of change of power has ideal characteristics for this purpose. It is firmly based upon theories of fluid dynamics and its derivation is free of assumptions related to heart structure and function. It is measured as p dQ/dt + Q dp/dt, where p = pressure and Q = flow. When measured at peak tension, the ejection rate of change of power was (12.3 +/- 0.8) X 10(8) dynes cm sec-2 in 11 patients with abnormal ventricular performance (P less than 0.001). Studies in dogs showed no effect of preload or afterload. This suggests a relation to characteristics of muscle fibers, which was shown. If one assumes a thin wall sphere, the ejection rate of change of power at peak tension reduces to the following function of tension (T), fiber length (2 pi r), and rate of shortening (2 pi dr/dt): d(power)/dt = 8 pi T](dr/dt)2 + r d2r/dt2[. Thus, the contractile characteristics of muscle fibers (force, velocity and tension) are related in an uncomplicated fashion by a single and highly discriminating hemodynamic indicator of ventricular performance, the ejection rate of change of ventricular power measured at peak tension."} {"id": "PMID:1266754", "title": "Definition of myocardial perfusion by continuous infusion of krypton-81m.", "content": "Krypton-81m, a radionuclide emitting a 190 kev gamma ray, has a half-life of 13 seconds. It is a radioisotope of an inert water-soluble noble gas and is produced at a constant rate by spontaneous decay of rubidium-81 in an 81Rb-81mKr generator-delivery system. Delivery is through a minibore Teflon catheter that can be threaded through a standard no. 7 or 8F angiographic catheter. The generator is eluted by 5 percent dextrose-in-water, delivered by infusion pump at 1.5 ml/min, and the eluate is infused intraarterially directly into any organ. Delivery and decay reach equilibrium within 2 minutes, producing a heterogeneous distribution that is proportional to the perfusibility of the tissue concerned and the time required to reach it. The ultrashort halflife of the radionuclide rapidly eliminates activity when delivery ceases; thus, experiments can be sequentially repeated at brief intervals. The radiation hazard for easily imaged doses is negligible. Preliminary studies in open chest dogs were visualized by scintillation camera, stored on digital data disk, processed, and displayed in dual channel, dual color mode on a video system. Images of myocardial perfusion defined relative levels of perfusion, collateral circulation between coronary arterial branches, equilibrium time of diffusible perfusion of the myocardium, focal defects in induced occlusion, collateral circulation to occlusion, and reactive hyperemia after release of induced coronary occlusion. The system and technique appear applicable to human subjects.", "contents": "Definition of myocardial perfusion by continuous infusion of krypton-81m. Krypton-81m, a radionuclide emitting a 190 kev gamma ray, has a half-life of 13 seconds. It is a radioisotope of an inert water-soluble noble gas and is produced at a constant rate by spontaneous decay of rubidium-81 in an 81Rb-81mKr generator-delivery system. Delivery is through a minibore Teflon catheter that can be threaded through a standard no. 7 or 8F angiographic catheter. The generator is eluted by 5 percent dextrose-in-water, delivered by infusion pump at 1.5 ml/min, and the eluate is infused intraarterially directly into any organ. Delivery and decay reach equilibrium within 2 minutes, producing a heterogeneous distribution that is proportional to the perfusibility of the tissue concerned and the time required to reach it. The ultrashort halflife of the radionuclide rapidly eliminates activity when delivery ceases; thus, experiments can be sequentially repeated at brief intervals. The radiation hazard for easily imaged doses is negligible. Preliminary studies in open chest dogs were visualized by scintillation camera, stored on digital data disk, processed, and displayed in dual channel, dual color mode on a video system. Images of myocardial perfusion defined relative levels of perfusion, collateral circulation between coronary arterial branches, equilibrium time of diffusible perfusion of the myocardium, focal defects in induced occlusion, collateral circulation to occlusion, and reactive hyperemia after release of induced coronary occlusion. The system and technique appear applicable to human subjects."} {"id": "PMID:1266755", "title": "Unstable angina pectoris: national cooperative study group to compare medical and surgical therapy. I. Report of protocol and patient population.", "content": "A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the eithical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris.", "contents": "Unstable angina pectoris: national cooperative study group to compare medical and surgical therapy. I. Report of protocol and patient population. A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the eithical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris."} {"id": "PMID:1266756", "title": "Multivariate prediction of coronary heart disease during 8.5 year follow-up in the Western Collaborative Group Study.", "content": "The Western Collaborative Group Study is a prospective study of 3,154 employed men aged 39 to 59 years. Ischemic heart disease occurred in 257 subjects during 8.5 years of follow-up. Risk of coronary heart disease was studied with use of the multiple logistic risk model. The incidence of coronary heart disease had a highly significant association with serum cholesterol level, behavior pattern, cigarette smoking and systolic blood pressure in younger (39 to 49 years) and older (50 to 59 years) men and also with age and corneal arcus in the younger group. Type A behavior pattern was strongly related to the incidence of coronary disease in both age groups, independent of interrelations of behavior patterns with any other risk factor.", "contents": "Multivariate prediction of coronary heart disease during 8.5 year follow-up in the Western Collaborative Group Study. The Western Collaborative Group Study is a prospective study of 3,154 employed men aged 39 to 59 years. Ischemic heart disease occurred in 257 subjects during 8.5 years of follow-up. Risk of coronary heart disease was studied with use of the multiple logistic risk model. The incidence of coronary heart disease had a highly significant association with serum cholesterol level, behavior pattern, cigarette smoking and systolic blood pressure in younger (39 to 49 years) and older (50 to 59 years) men and also with age and corneal arcus in the younger group. Type A behavior pattern was strongly related to the incidence of coronary disease in both age groups, independent of interrelations of behavior patterns with any other risk factor."} {"id": "PMID:1266757", "title": "Acute coronary embolism complicating bacterial endocarditis: operative treatment.", "content": "A patient with bacterial endocarditis and no previous history of angina substained an acute anterolateral myocardial infarction while awaiting surgery. Selective coronary arteriography revealed a filling defect in the left anterior descending coronary artery with limited flow beyond the area of occlusion. A calcific embolus from the infected aortic valve was removed at the time of valve replacement, and the patient had an uneventful immediate postoperative course. Late postoperatively paravalvular aortic regurgitation recurred before and after a second repair.", "contents": "Acute coronary embolism complicating bacterial endocarditis: operative treatment. A patient with bacterial endocarditis and no previous history of angina substained an acute anterolateral myocardial infarction while awaiting surgery. Selective coronary arteriography revealed a filling defect in the left anterior descending coronary artery with limited flow beyond the area of occlusion. A calcific embolus from the infected aortic valve was removed at the time of valve replacement, and the patient had an uneventful immediate postoperative course. Late postoperatively paravalvular aortic regurgitation recurred before and after a second repair."} {"id": "PMID:1266758", "title": "Repetitive myocardial ischemia of Prinzmetal type without angina pectoris.", "content": "In a patient with a normal electrocardiogram, normal treadmill exercise test, normal coronary arteriogram and no symptoms to suggest angina pectoris, continuous monitoring during several days exhibited repetitive (one to two per hour) S-T segment elevations in the precordial electrocardiographic leads and hemodynamic changes typical of Prinzmetal's angina (reduction in arterial pressure and cardiac index and increase in systemic peripheral resistance and pulmonary wedge pressure). This case demonstrates that electrical and dynamic cardiac alterations of Prinzmetal's angina can occur even in the absence of angina pectoris.", "contents": "Repetitive myocardial ischemia of Prinzmetal type without angina pectoris. In a patient with a normal electrocardiogram, normal treadmill exercise test, normal coronary arteriogram and no symptoms to suggest angina pectoris, continuous monitoring during several days exhibited repetitive (one to two per hour) S-T segment elevations in the precordial electrocardiographic leads and hemodynamic changes typical of Prinzmetal's angina (reduction in arterial pressure and cardiac index and increase in systemic peripheral resistance and pulmonary wedge pressure). This case demonstrates that electrical and dynamic cardiac alterations of Prinzmetal's angina can occur even in the absence of angina pectoris."} {"id": "PMID:1266759", "title": "Pulmonary varix regression after mitral valve replacement.", "content": "Pulmonary varix is a rare finding; only 35 documented cases have been reported. The first case was described in 1843 as an icidental postmortem finding. The first clinical diagnosis was not made until 1951. In more than half of the 35 cases, the varix was present in the absence of congenital and acquired heart disease. Six patients have had concomitant mitral rheumatic heart disease. This communication describes the second patient with rheumatic mitral regurgitation in whom the pulmonary varix became radiographically invisible after prosthetic mitral valve replacement.", "contents": "Pulmonary varix regression after mitral valve replacement. Pulmonary varix is a rare finding; only 35 documented cases have been reported. The first case was described in 1843 as an icidental postmortem finding. The first clinical diagnosis was not made until 1951. In more than half of the 35 cases, the varix was present in the absence of congenital and acquired heart disease. Six patients have had concomitant mitral rheumatic heart disease. This communication describes the second patient with rheumatic mitral regurgitation in whom the pulmonary varix became radiographically invisible after prosthetic mitral valve replacement."} {"id": "PMID:1266760", "title": "Myotonia dystrophica: ventricular arrhythmias, intraventricular conduction abnormalities, atrioventricular block and Stokes-Adams attacks successfully treated with permanent transvenous pacemaker.", "content": "In a patient with myotonia dystrophica multiple ventricular arrhythmias and high degree atrioventricular block requiring a permanent pacemaker developed. Patients with skeletal muscle disease may present with disproportionately advanced manifestations of associated cardiac disease. Early recognition of potential serious underlying cardiac disease is important in patients with this condition.", "contents": "Myotonia dystrophica: ventricular arrhythmias, intraventricular conduction abnormalities, atrioventricular block and Stokes-Adams attacks successfully treated with permanent transvenous pacemaker. In a patient with myotonia dystrophica multiple ventricular arrhythmias and high degree atrioventricular block requiring a permanent pacemaker developed. Patients with skeletal muscle disease may present with disproportionately advanced manifestations of associated cardiac disease. Early recognition of potential serious underlying cardiac disease is important in patients with this condition."} {"id": "PMID:1266772", "title": "Fine structure of differentiating ameloblasts in the kitten.", "content": "The fine structure of differentiating ameloblasts was studied in the lower second molar of 1-week-old kittens after perfusion fixation with and without subsequent decalcification. The differentiation zone was divided into three phases. In Differentiation 1, ameloblasts are about 27 mum long and face an uninterrupted basal lamina. The predentin adjacent to the basal lamina contains a few collagen fibrils oriented mainly at right angles to the ameloblast surface. The specialized predentin forms a well-defined layer, up to 1.5 mum thick, referred to as the junctional layer. In Differentiation 2, ameloblast processes extend through the basal lamina and the thickness of the junctional layer. The processes consist of cytoplasmic sheets forming a honeycomb-like network. Dentin starts to calcify after process-formation is underway. Two distinct types of odontoblast processes, having different shapes and contents, come in contact with the ameloblasts and push into the ameloblastic layer. In Differentiation 3, stippled material appears in the extracellular spaces between ameloblasts. Later, stippled material-like substances appear in the predentin close to the ameloblast apex and close to odontoblast processes within the dentin. Ameloblasts now are up to 40 mum high. Enamel secretion starts in small circumscribed areas which gradually enlarge, leading to the disappearance of the ameloblast processes. These findings are compared with results obtained in other species, including man, and their possible functional significance is discussed.", "contents": "Fine structure of differentiating ameloblasts in the kitten. The fine structure of differentiating ameloblasts was studied in the lower second molar of 1-week-old kittens after perfusion fixation with and without subsequent decalcification. The differentiation zone was divided into three phases. In Differentiation 1, ameloblasts are about 27 mum long and face an uninterrupted basal lamina. The predentin adjacent to the basal lamina contains a few collagen fibrils oriented mainly at right angles to the ameloblast surface. The specialized predentin forms a well-defined layer, up to 1.5 mum thick, referred to as the junctional layer. In Differentiation 2, ameloblast processes extend through the basal lamina and the thickness of the junctional layer. The processes consist of cytoplasmic sheets forming a honeycomb-like network. Dentin starts to calcify after process-formation is underway. Two distinct types of odontoblast processes, having different shapes and contents, come in contact with the ameloblasts and push into the ameloblastic layer. In Differentiation 3, stippled material appears in the extracellular spaces between ameloblasts. Later, stippled material-like substances appear in the predentin close to the ameloblast apex and close to odontoblast processes within the dentin. Ameloblasts now are up to 40 mum high. Enamel secretion starts in small circumscribed areas which gradually enlarge, leading to the disappearance of the ameloblast processes. These findings are compared with results obtained in other species, including man, and their possible functional significance is discussed."} {"id": "PMID:1266773", "title": "An angiographic study of the carotid arterial and jugular venous systems in the cat.", "content": "Standard techniques for performing carotid angiography in dogs and in man were adapted to the cat in order to study the vascularization of both intracranial and extracranial structures. Venous drainage was examined by venography of selected vessels. The carotid-cerebral and the vertebral-basilar arterial systems of the cat were studied, although no attempt was made to define the territory supplied by each system. In serial angiograms, vascularization of the rete mirabile conjugatum was visualized and distinct arterial and venous retia were delineated. Large facial veins were seen approximately one second after the intra-arterial injection of radio-contrast material. The early filling of the large facial veins appeared to be the result of an artery-to-venous shunt. Contrast material flowed posteriorly in these veins and drained into the venous rete. When contrast material was injected either into the sagittal sinus or retrograde in the external jugular vein, the internal jugular vein was visible in four of ten cats. This vessel drained blood directly from intracranial contents before anastomosis with the vertebral and external jugular veins.", "contents": "An angiographic study of the carotid arterial and jugular venous systems in the cat. Standard techniques for performing carotid angiography in dogs and in man were adapted to the cat in order to study the vascularization of both intracranial and extracranial structures. Venous drainage was examined by venography of selected vessels. The carotid-cerebral and the vertebral-basilar arterial systems of the cat were studied, although no attempt was made to define the territory supplied by each system. In serial angiograms, vascularization of the rete mirabile conjugatum was visualized and distinct arterial and venous retia were delineated. Large facial veins were seen approximately one second after the intra-arterial injection of radio-contrast material. The early filling of the large facial veins appeared to be the result of an artery-to-venous shunt. Contrast material flowed posteriorly in these veins and drained into the venous rete. When contrast material was injected either into the sagittal sinus or retrograde in the external jugular vein, the internal jugular vein was visible in four of ten cats. This vessel drained blood directly from intracranial contents before anastomosis with the vertebral and external jugular veins."} {"id": "PMID:1266774", "title": "Immunological competence in Snell-Bagg pituitary dwarf mice: response to the contact-sensitizing agent oxazolone.", "content": "Snell-Bagg pituitary dwarf mice are an autosomal recessive mutant, their dwarfism being the result of an anterior pituitary defect. A number of investigators have reported that these mice, in addition to having hormonal deficiencies, have immunological defects. Dwarf mice reject allogenic skin grafts slowly, show a reduced response to contact agents and decreased graft-vs-host reactivity. Other investigators have suggested that these results indicate a thymus-cell-deficiency. Contrary to this conclusion, we have found that the thymuses in our dwarf mice have a normal cellular composition and the T-cell-dependent zones in the peripheral lymphoid tissues are not deficient in the lymphocytes. Therefore, this investigation was undertaken to study the response of dwarf mice to the hapten, oxazolone, which produces one type of T-cell-dependent response, delayed hypersensitivity, and to compare this response to that of normal littermates in animals 15 to 90 days of age.", "contents": "Immunological competence in Snell-Bagg pituitary dwarf mice: response to the contact-sensitizing agent oxazolone. Snell-Bagg pituitary dwarf mice are an autosomal recessive mutant, their dwarfism being the result of an anterior pituitary defect. A number of investigators have reported that these mice, in addition to having hormonal deficiencies, have immunological defects. Dwarf mice reject allogenic skin grafts slowly, show a reduced response to contact agents and decreased graft-vs-host reactivity. Other investigators have suggested that these results indicate a thymus-cell-deficiency. Contrary to this conclusion, we have found that the thymuses in our dwarf mice have a normal cellular composition and the T-cell-dependent zones in the peripheral lymphoid tissues are not deficient in the lymphocytes. Therefore, this investigation was undertaken to study the response of dwarf mice to the hapten, oxazolone, which produces one type of T-cell-dependent response, delayed hypersensitivity, and to compare this response to that of normal littermates in animals 15 to 90 days of age."} {"id": "PMID:1266775", "title": "Proliferative kinetics of large and small intraepithelial lymphocytes in the small intestine of the mouse.", "content": "The proliferative kinetics of the intraepithelial lymphocytes (IL) of the mouse intestine have been evaluated. By inducing mitotic arrest it was found that large IL - constituting about 50% of the IL - showed a mitotic rate of 2.3. Autoradiographic results obtained after two different schedules of 3H-thymidine injections showed that 30% of the large IL were in DNA synthesis, and that the large IL were renewed at a rate comparable to that of blast cells from Peyer's patches, mesenteric lymph nodes and thoracic duct lymph. The small IL were renewed very rapidly compared to small lymphocytes of peripheral lymphoid tissues, although small lymphocytes with lifespans of several weeks were also present in the epithelial sheet. By the use of intestinal perfusion, in vivo, it was estimated that the loss of lymphocytes from intestinal villi into the lumen of the gut was negligible, and it is concluded that the most probable kinetic model for the majority of IL is: B and T lymphoblasts invade the epithelium and undergo mitosis. B lymphoblasts give rise predominantly to plasma cells, and T lymphoblasts give rise to small lymphocytes - probably long-lived - which reenter the circulation.", "contents": "Proliferative kinetics of large and small intraepithelial lymphocytes in the small intestine of the mouse. The proliferative kinetics of the intraepithelial lymphocytes (IL) of the mouse intestine have been evaluated. By inducing mitotic arrest it was found that large IL - constituting about 50% of the IL - showed a mitotic rate of 2.3. Autoradiographic results obtained after two different schedules of 3H-thymidine injections showed that 30% of the large IL were in DNA synthesis, and that the large IL were renewed at a rate comparable to that of blast cells from Peyer's patches, mesenteric lymph nodes and thoracic duct lymph. The small IL were renewed very rapidly compared to small lymphocytes of peripheral lymphoid tissues, although small lymphocytes with lifespans of several weeks were also present in the epithelial sheet. By the use of intestinal perfusion, in vivo, it was estimated that the loss of lymphocytes from intestinal villi into the lumen of the gut was negligible, and it is concluded that the most probable kinetic model for the majority of IL is: B and T lymphoblasts invade the epithelium and undergo mitosis. B lymphoblasts give rise predominantly to plasma cells, and T lymphoblasts give rise to small lymphocytes - probably long-lived - which reenter the circulation."} {"id": "PMID:1266776", "title": "An electron microscopic study of the closure of the optic fissure in the golden hamster.", "content": "During early development of the mammalian eye, invagination and differential growth result in the formation of a cleft, the optic fissure, through which the hyaloid artery reaches the interior of the optic cup. Closure of this fissure was studied by electron microscopy in hamster embryos from days 10 through 12 of gestation. Closure occurred only when and where the basal lamina, which invests the entire wall of the optic cup, had disappeared. No morphological evidence was found that indicated a mechanism for the breakdown of the basal lamina lining the fissure, the fusion of surface cells of opposing sides and restoration of the basal lamina along inner and outer margins of the wall after closure. While in previous light microscopic investigations of the developing human eye eversion of the inner layer into the fissure has been reported, an inversion of the outer layer was found in this study. During inversion cells of the outer layer temporarily changed their orientation. While most of these cells remained within the layer when it returned to its normal position, some cells became separated and degenerated. Inversion of the outer layer, breakdown of the basal lamina and degeneration of superfluous cells appear to be necessary events for a normal closure to occur.", "contents": "An electron microscopic study of the closure of the optic fissure in the golden hamster. During early development of the mammalian eye, invagination and differential growth result in the formation of a cleft, the optic fissure, through which the hyaloid artery reaches the interior of the optic cup. Closure of this fissure was studied by electron microscopy in hamster embryos from days 10 through 12 of gestation. Closure occurred only when and where the basal lamina, which invests the entire wall of the optic cup, had disappeared. No morphological evidence was found that indicated a mechanism for the breakdown of the basal lamina lining the fissure, the fusion of surface cells of opposing sides and restoration of the basal lamina along inner and outer margins of the wall after closure. While in previous light microscopic investigations of the developing human eye eversion of the inner layer into the fissure has been reported, an inversion of the outer layer was found in this study. During inversion cells of the outer layer temporarily changed their orientation. While most of these cells remained within the layer when it returned to its normal position, some cells became separated and degenerated. Inversion of the outer layer, breakdown of the basal lamina and degeneration of superfluous cells appear to be necessary events for a normal closure to occur."} {"id": "PMID:1266777", "title": "The effect of frozen ovarian autografts on compensatory ovulation and steroid production in unilaterally ovariectomized rats.", "content": "In the present study rats were unilaterally ovariectomized (ULO) and the surgically removed ovary was frozen for 13 days. After allowing the remaining ovary to compensate with respect to number of ova shed, the frozen graft was thawed and transplanted subcutaneously to determine the effect on ovulation number, cycle length, uterine weight, ovarian weight and plasma levels of estradiol-17beta (E2) and progesterone. Rats ULO at 45 days of age, which received an autograft 13 days later, had a decrease in the number of eggs shed as compared to control ULO rats (6.4 +/- 0.8 vs. 11.1 +/- 0.9 eggs, respectively) and a decrease in plasma E2 (14.5 +/- 1.7 VS. 21.0 +/- 1.5 PG/ML, respectively). No differences were observed in progesterone concentration, uterine weight, ovarian weight or cycle length. In contrast, rats ULO at 31 days of age, which received an autograft 13 days later, showed no differences in comparison to control ULO rats. Castrates which received ovarian autografts developed cycling vaginal smears and had increased E2 (31.9 +/- 4.3 pg/ml) and decreased progesterone (18.3 +/- 1.9 ng/ml) levels. Since ULO animals with autografts shed fewer ova, the present study demonstrates that the amount of ovarian tissue influences ovulation number either by utilization of gonadotropins or by an, as yet, undefined mechanism.", "contents": "The effect of frozen ovarian autografts on compensatory ovulation and steroid production in unilaterally ovariectomized rats. In the present study rats were unilaterally ovariectomized (ULO) and the surgically removed ovary was frozen for 13 days. After allowing the remaining ovary to compensate with respect to number of ova shed, the frozen graft was thawed and transplanted subcutaneously to determine the effect on ovulation number, cycle length, uterine weight, ovarian weight and plasma levels of estradiol-17beta (E2) and progesterone. Rats ULO at 45 days of age, which received an autograft 13 days later, had a decrease in the number of eggs shed as compared to control ULO rats (6.4 +/- 0.8 vs. 11.1 +/- 0.9 eggs, respectively) and a decrease in plasma E2 (14.5 +/- 1.7 VS. 21.0 +/- 1.5 PG/ML, respectively). No differences were observed in progesterone concentration, uterine weight, ovarian weight or cycle length. In contrast, rats ULO at 31 days of age, which received an autograft 13 days later, showed no differences in comparison to control ULO rats. Castrates which received ovarian autografts developed cycling vaginal smears and had increased E2 (31.9 +/- 4.3 pg/ml) and decreased progesterone (18.3 +/- 1.9 ng/ml) levels. Since ULO animals with autografts shed fewer ova, the present study demonstrates that the amount of ovarian tissue influences ovulation number either by utilization of gonadotropins or by an, as yet, undefined mechanism."} {"id": "PMID:1266778", "title": "Renal vasculature of the trout demonstrated by scanning electron microscopy, compared with canine glomerular vessels.", "content": "In order to gain additional information regarding renal circulatory patterns, we have used both ink and resin injections to study the arterial supply to the mesonephric kidney of trout. Arterial injections through the dorsal aorta with ink were made for histological preparations in which the length, termination and relationship of glomerular vessels were examined. Similar injections with methyl methacrylate were made in preparation of corrosion casts to provide us with gross replicas of the aortic branches to the kidney as well as casts of glomerular structure for scanning electron microscopy. The sequence of vessels through which arterial blood passed to the renal corpuscle and ultimately to the uriniferous tubules was traced. Each afferent arteriole was found to terminate in three to six branches which formed anastomosing circuits of capillaries; these vessels reunited at the hilum to form a single efferent arteriole. The efferent arterioles in trun traveled a short distance to peritubular capillary beds and sinusoids. Morphological evidence was found for preglomerular sphincter-like action only. The glomerular vessels were found to be similar to, although less complex than, those of the outer and mid-cortical regions of the dog kidney.", "contents": "Renal vasculature of the trout demonstrated by scanning electron microscopy, compared with canine glomerular vessels. In order to gain additional information regarding renal circulatory patterns, we have used both ink and resin injections to study the arterial supply to the mesonephric kidney of trout. Arterial injections through the dorsal aorta with ink were made for histological preparations in which the length, termination and relationship of glomerular vessels were examined. Similar injections with methyl methacrylate were made in preparation of corrosion casts to provide us with gross replicas of the aortic branches to the kidney as well as casts of glomerular structure for scanning electron microscopy. The sequence of vessels through which arterial blood passed to the renal corpuscle and ultimately to the uriniferous tubules was traced. Each afferent arteriole was found to terminate in three to six branches which formed anastomosing circuits of capillaries; these vessels reunited at the hilum to form a single efferent arteriole. The efferent arterioles in trun traveled a short distance to peritubular capillary beds and sinusoids. Morphological evidence was found for preglomerular sphincter-like action only. The glomerular vessels were found to be similar to, although less complex than, those of the outer and mid-cortical regions of the dog kidney."} {"id": "PMID:1266779", "title": "Quantitative analysis of muscle cell changes in compensatory hypertrophy and work-induced hypertrophy.", "content": "The cytological characteristics of two modes of muscle hypertrophy were studied in the extensor digitorum longus muscle of the rat. Comprensatory hypertrophy (CH) was produced by tenotomy of the tibialis anterior muscle and work-induced hypertrophy (WIH) was produced by forced swimming of the animal. While both methods produced an increase in muscle weight and cell size, these two parameters did not correlate. Morphometric analyses of the hypertrophied muscle cells demonstrated that in CH-muscle there was an increase in mitochondrial volume density, a decrease in myofibrillar volume density and no change in sarcotubular or nuclear volume density. WIH-muscle demonstrated an increase in sarcotubular volume density but no change in mitochondrial, myofibrillar or nuclear volume density. It is concluded that in CH-muscle, the cell volume increase is attributable to mitochondrial volume increase and that there is no increase in the contratile myofibrillar component of the cell. WIH-muscle, on the other hand, has a cell volume increase which is attributable to a proportional increase in these organelles.", "contents": "Quantitative analysis of muscle cell changes in compensatory hypertrophy and work-induced hypertrophy. The cytological characteristics of two modes of muscle hypertrophy were studied in the extensor digitorum longus muscle of the rat. Comprensatory hypertrophy (CH) was produced by tenotomy of the tibialis anterior muscle and work-induced hypertrophy (WIH) was produced by forced swimming of the animal. While both methods produced an increase in muscle weight and cell size, these two parameters did not correlate. Morphometric analyses of the hypertrophied muscle cells demonstrated that in CH-muscle there was an increase in mitochondrial volume density, a decrease in myofibrillar volume density and no change in sarcotubular or nuclear volume density. WIH-muscle demonstrated an increase in sarcotubular volume density but no change in mitochondrial, myofibrillar or nuclear volume density. It is concluded that in CH-muscle, the cell volume increase is attributable to mitochondrial volume increase and that there is no increase in the contratile myofibrillar component of the cell. WIH-muscle, on the other hand, has a cell volume increase which is attributable to a proportional increase in these organelles."} {"id": "PMID:1266780", "title": "The hypothalamic magnocellular neurosecretory system of the guinea pig. III. Ultrastructure of the fetal neural lobe.", "content": "The ultrastructure of the fetal guinea pig neural lobe was studied from day 40 to day 60 of gestation. Pituitaries were taken every five days and at least four glands from each gestational period were examined. Bundles of nerve fibers had invaded the periphery of the gland on day 40. By day 50 axon profiles were distributed throughout the entire posterior pituitary though pituicyte processes continued to act as a barrier between axons and the perivascular space of capillaries. Neural processes established contact with the capillaries between days 55 and 60. Neurosecretory granules (NSG) were present within a few axons on day 40. The number of axons with NSG and the total quantity of granules increased gradually throughout fetal development. Electron-lucent granules (microvesicles) were observed infrequently until the day of birth. A population of dense-cored vesicles, 70-80 mmu in diameter, was present from day 50 onward; a second population with larger diameters was also present throughout the developmental sequence and these increased from 90-130 mmu in diameter to 170-220 mmu in diameter between days 40 to 60. The presence of neurosecretory granules is discussed in relation to the onset of synthesis and storage of neurohypophysial hormones.", "contents": "The hypothalamic magnocellular neurosecretory system of the guinea pig. III. Ultrastructure of the fetal neural lobe. The ultrastructure of the fetal guinea pig neural lobe was studied from day 40 to day 60 of gestation. Pituitaries were taken every five days and at least four glands from each gestational period were examined. Bundles of nerve fibers had invaded the periphery of the gland on day 40. By day 50 axon profiles were distributed throughout the entire posterior pituitary though pituicyte processes continued to act as a barrier between axons and the perivascular space of capillaries. Neural processes established contact with the capillaries between days 55 and 60. Neurosecretory granules (NSG) were present within a few axons on day 40. The number of axons with NSG and the total quantity of granules increased gradually throughout fetal development. Electron-lucent granules (microvesicles) were observed infrequently until the day of birth. A population of dense-cored vesicles, 70-80 mmu in diameter, was present from day 50 onward; a second population with larger diameters was also present throughout the developmental sequence and these increased from 90-130 mmu in diameter to 170-220 mmu in diameter between days 40 to 60. The presence of neurosecretory granules is discussed in relation to the onset of synthesis and storage of neurohypophysial hormones."} {"id": "PMID:1266783", "title": "Amino acid levels across normal forearm muscle and splanchnic bed after a protein meal.", "content": "To characterize further the role of blood cells in amino acid transport, four normal volunteers were asked to ingest 200 g of broiled ground sirloin within a 10-min period. Blood samples from a radial artery, a deep vein draining forearm muscle bed, and a tributary of the hepatic vein were obtained prior to and for 4 hr after the meal and analyzed for various hormones and substrates. At rest, analysis of arterio-deep venous differences across the forearm revealed the blood cell and plasma amino acid compartmentmental contents to be relatively constant except for alanine and glutamine. Whole blood arterio-hepatic venous (A-HV) amino acid differences were not significantly different from zero; however, blood cell A-HV difference analysis revealed a significant release of threonine from the splanchnic bed while plasma A-HV difference analysis revealed modest but significant releases of glutamate and ornithine and uptakes of phenylalanine and histidine. After the ingestion of the meat meal, plasma and blood cell levels of almost all of the measured amino acids increased significantly. Notable exceptions included glycine and alanine, levels of which did not change significantly and glutamine. The arterial blood cell content of the latter amino acid paradoxically decreased while arterial plasma levels increased significantly. Most importantly, large quantities of branched chain amino acids were released from the splanchnic bed and removed by forearm muscle. These data suggest that the blood cells of normal man do actively participate in amino acid transport, and that the magnitude and direction of change induced by the ingestion of a proteins meal varies with the individual amino acid.", "contents": "Amino acid levels across normal forearm muscle and splanchnic bed after a protein meal. To characterize further the role of blood cells in amino acid transport, four normal volunteers were asked to ingest 200 g of broiled ground sirloin within a 10-min period. Blood samples from a radial artery, a deep vein draining forearm muscle bed, and a tributary of the hepatic vein were obtained prior to and for 4 hr after the meal and analyzed for various hormones and substrates. At rest, analysis of arterio-deep venous differences across the forearm revealed the blood cell and plasma amino acid compartmentmental contents to be relatively constant except for alanine and glutamine. Whole blood arterio-hepatic venous (A-HV) amino acid differences were not significantly different from zero; however, blood cell A-HV difference analysis revealed a significant release of threonine from the splanchnic bed while plasma A-HV difference analysis revealed modest but significant releases of glutamate and ornithine and uptakes of phenylalanine and histidine. After the ingestion of the meat meal, plasma and blood cell levels of almost all of the measured amino acids increased significantly. Notable exceptions included glycine and alanine, levels of which did not change significantly and glutamine. The arterial blood cell content of the latter amino acid paradoxically decreased while arterial plasma levels increased significantly. Most importantly, large quantities of branched chain amino acids were released from the splanchnic bed and removed by forearm muscle. These data suggest that the blood cells of normal man do actively participate in amino acid transport, and that the magnitude and direction of change induced by the ingestion of a proteins meal varies with the individual amino acid."} {"id": "PMID:1266784", "title": "Treatment of children with phenylketonuria using a phenylalanine-free protein hydrolysate (Albumaid XP).", "content": "Albumaid XP, a phenylalanine-free protein hydrolysate, was used for treatment of five phenylketonuric infants born between January, 1970, and September, 1972. The results were compared with those obtained from the five infants most recently treated with Lofenalac in our clinic prior to 1970. Treatment was begun by 2 months of age in all instances. Satisfactory physical growth and mental development were achieved using either Albumaid XP or Lofenalac, and there were no major differences in the outcomes with either treatment. The two protein sources may be used interchangeably for treatment of phenylketonuria.", "contents": "Treatment of children with phenylketonuria using a phenylalanine-free protein hydrolysate (Albumaid XP). Albumaid XP, a phenylalanine-free protein hydrolysate, was used for treatment of five phenylketonuric infants born between January, 1970, and September, 1972. The results were compared with those obtained from the five infants most recently treated with Lofenalac in our clinic prior to 1970. Treatment was begun by 2 months of age in all instances. Satisfactory physical growth and mental development were achieved using either Albumaid XP or Lofenalac, and there were no major differences in the outcomes with either treatment. The two protein sources may be used interchangeably for treatment of phenylketonuria."} {"id": "PMID:1266785", "title": "Neocortex development during severe malnutrition in the rat.", "content": "Histological methods (Golgi-Cox and Nissl) were used to study the maturation of the large pyramidal cells of layer V of the occipital cortex in malnourished rats (according to the method of Araya et al.). The main alterations were observed in pyramidal cells of cortical alyer V; These showed a decrease of the number and span of dendritic basilar processes. An increase in cell density was also observed in this layer. We assume that malnutrition during this period of development provokes a derangement which disturbs the process of neuron differentiation, with effects that probably are permanent.", "contents": "Neocortex development during severe malnutrition in the rat. Histological methods (Golgi-Cox and Nissl) were used to study the maturation of the large pyramidal cells of layer V of the occipital cortex in malnourished rats (according to the method of Araya et al.). The main alterations were observed in pyramidal cells of cortical alyer V; These showed a decrease of the number and span of dendritic basilar processes. An increase in cell density was also observed in this layer. We assume that malnutrition during this period of development provokes a derangement which disturbs the process of neuron differentiation, with effects that probably are permanent."} {"id": "PMID:1266786", "title": "Certain metabolic consequences of jejunoileal bypass.", "content": "Jejunoileal bypass for obesity has been shown to be associated with increased hepatic triglycerides during the period of brisk weight loss. The current report describes certain metabolic changes observed in 29 patients 21 months after bypass. Significant decreases in serum cholesterol, serum triglycerides, blood sugar after a glucose load, and fasting plasma insulin levels were noted. Increased oxalate excretion and occasional episodes of hypomagnesemia occurred. Repeated clinical and laboratory observations by a medical-surgical team offer the best opportunity to evaluate this procedure.", "contents": "Certain metabolic consequences of jejunoileal bypass. Jejunoileal bypass for obesity has been shown to be associated with increased hepatic triglycerides during the period of brisk weight loss. The current report describes certain metabolic changes observed in 29 patients 21 months after bypass. Significant decreases in serum cholesterol, serum triglycerides, blood sugar after a glucose load, and fasting plasma insulin levels were noted. Increased oxalate excretion and occasional episodes of hypomagnesemia occurred. Repeated clinical and laboratory observations by a medical-surgical team offer the best opportunity to evaluate this procedure."} {"id": "PMID:1266787", "title": "Zinc nutrition in celiac sprue.", "content": "Zinc nutritional status was examined in 10 adult patients with biopsy-proven celiac disease; five of these patients were clinically well on gluten-free diets at the time of study. Plasma zinc and taste acuity were used as indices of zinc nutrition. Depression of plasma zinc and lowered taste discrimination were observed among the untreated patients, and some patients who were otherwise in clinical remission also had impaired zinc nutrition. With confirmation of plasma copper depression in patients with celiac sprue, these observations indicate that trace metal deficiency is another common nutritional complication of adult celiac disease.", "contents": "Zinc nutrition in celiac sprue. Zinc nutritional status was examined in 10 adult patients with biopsy-proven celiac disease; five of these patients were clinically well on gluten-free diets at the time of study. Plasma zinc and taste acuity were used as indices of zinc nutrition. Depression of plasma zinc and lowered taste discrimination were observed among the untreated patients, and some patients who were otherwise in clinical remission also had impaired zinc nutrition. With confirmation of plasma copper depression in patients with celiac sprue, these observations indicate that trace metal deficiency is another common nutritional complication of adult celiac disease."} {"id": "PMID:1266788", "title": "Reversal of experimental essential fatty acid deficiency by cutaneous administration of safflower oil.", "content": "The intriguing observation that cutaneous application of essential fatty acid (EFA)-rich oil corrects the biochemical abnormalities of EFA deficiency was evaluated in EFA-deficient rats. Approximately 185 mg of safflower oil (140 mg of linoleic acid) were applied daily for 15 days to the kin of EFA-deficient rats. Before and after treatment with the safflower oil, the fatty acid patterns of plasma and erythrocyte phospholipid as well as of plasma triglyceride and cholesterol ester fractions were determined. The linoleic and arachidonic acid content of both plasma and erythrocyte phospholipid increased, while the eicosatrienoic acid content of both fractions decreased. The linoleic acid content of plasma triglyceride increased with safflower oil treatment, but little change occurred in the almost undetectable pretreatment levels of arachidonic and eicosatrienoic acid. In the plasma cholesterol ester fraction, arachidonic acid increased with treatment and eicosatrienoic acid decreased, but the small increase in the linoleic acid content was not statistically significant. Thus, the study confirms the observation that cutaneous application of EFA-rich oils reverses the plasma biochemical manifestation of EFA deficiency. In addition cutaneously applied EFA-rich oils reversed the biochemical manifestations of EFA deficiency in erythrocytes. Whether or not cutaneous application of such oils will prevent EFA deficiency, however, remains to be proven.", "contents": "Reversal of experimental essential fatty acid deficiency by cutaneous administration of safflower oil. The intriguing observation that cutaneous application of essential fatty acid (EFA)-rich oil corrects the biochemical abnormalities of EFA deficiency was evaluated in EFA-deficient rats. Approximately 185 mg of safflower oil (140 mg of linoleic acid) were applied daily for 15 days to the kin of EFA-deficient rats. Before and after treatment with the safflower oil, the fatty acid patterns of plasma and erythrocyte phospholipid as well as of plasma triglyceride and cholesterol ester fractions were determined. The linoleic and arachidonic acid content of both plasma and erythrocyte phospholipid increased, while the eicosatrienoic acid content of both fractions decreased. The linoleic acid content of plasma triglyceride increased with safflower oil treatment, but little change occurred in the almost undetectable pretreatment levels of arachidonic and eicosatrienoic acid. In the plasma cholesterol ester fraction, arachidonic acid increased with treatment and eicosatrienoic acid decreased, but the small increase in the linoleic acid content was not statistically significant. Thus, the study confirms the observation that cutaneous application of EFA-rich oils reverses the plasma biochemical manifestation of EFA deficiency. In addition cutaneously applied EFA-rich oils reversed the biochemical manifestations of EFA deficiency in erythrocytes. Whether or not cutaneous application of such oils will prevent EFA deficiency, however, remains to be proven."} {"id": "PMID:1266789", "title": "A method for qualitative identification of sugars and semiquantitative determination of lactose content suitable for a variety of foods.", "content": "A semiquantitative chromatographic technique was developed and standardized using water/chloroform extracts of foods which are spotted onto heat-activated silica gel thin layer chromatographic (TLC) plates, run in butanol/acetic acid/ether/water, developed in acids anisaldehyde, and quantitated planimetrically using Purdy and Truter's formula. Clinically significant amounts of lactose were found in low-calorie sweeteners, breads, yogurt, margarine, penicillin, Gantrisin, and other commonly ingested nondairy substances.", "contents": "A method for qualitative identification of sugars and semiquantitative determination of lactose content suitable for a variety of foods. A semiquantitative chromatographic technique was developed and standardized using water/chloroform extracts of foods which are spotted onto heat-activated silica gel thin layer chromatographic (TLC) plates, run in butanol/acetic acid/ether/water, developed in acids anisaldehyde, and quantitated planimetrically using Purdy and Truter's formula. Clinically significant amounts of lactose were found in low-calorie sweeteners, breads, yogurt, margarine, penicillin, Gantrisin, and other commonly ingested nondairy substances."} {"id": "PMID:1266792", "title": "Efficacy of diet and exercise in the reduction of serum cholesterol and triglyceride in free-living adult males.", "content": "Young males with levels of serum cholesterol or triglyceride in the upper quartile of the distribution for volunteers tested, participated in a program designed to determine the effect of diet and exercise on serum lipids. Dietary modifications involved caloric restriction superimposed on either the National Institutes of Health (NIH) recommendations for type II or IV hyperlipoproteinemia, as appropriate, or superimposed on a fat-controlled regimen in which fat of an unspecified nature was restricted to 30% of total calories. Participants with elevated levels of cholesterol responded significantly better when instructed in the diet meeting NIH criteria, 21% change in cholesterol, than when instructed in a diet controlled in fat, 11% change in cholesterol. For those with elevated levels of triglyceride, the NIH type IV diet was no more effective at the end of 6 months than the diet controlled in fat where caloric restriction was a part of both dietary regimens. The mean change in triglyceride for this group was 32%. Those with elevated levels of both cholesterol and triglyceride were less amenable to change than those with a single hyperlipidemia. For some diagnostic types, the results were suggestive of a beneficial effect of exercise in addition to diet in accelerating or maintaining reductions in serum lipids.", "contents": "Efficacy of diet and exercise in the reduction of serum cholesterol and triglyceride in free-living adult males. Young males with levels of serum cholesterol or triglyceride in the upper quartile of the distribution for volunteers tested, participated in a program designed to determine the effect of diet and exercise on serum lipids. Dietary modifications involved caloric restriction superimposed on either the National Institutes of Health (NIH) recommendations for type II or IV hyperlipoproteinemia, as appropriate, or superimposed on a fat-controlled regimen in which fat of an unspecified nature was restricted to 30% of total calories. Participants with elevated levels of cholesterol responded significantly better when instructed in the diet meeting NIH criteria, 21% change in cholesterol, than when instructed in a diet controlled in fat, 11% change in cholesterol. For those with elevated levels of triglyceride, the NIH type IV diet was no more effective at the end of 6 months than the diet controlled in fat where caloric restriction was a part of both dietary regimens. The mean change in triglyceride for this group was 32%. Those with elevated levels of both cholesterol and triglyceride were less amenable to change than those with a single hyperlipidemia. For some diagnostic types, the results were suggestive of a beneficial effect of exercise in addition to diet in accelerating or maintaining reductions in serum lipids."} {"id": "PMID:1266793", "title": "Protein status of the elderly as measured by dietary intake, hair tissue, and serum albumin.", "content": "The nutritional status of 95 Medicare-age individuals was evaluated by dietary intake, physical condition, and components of urine, blood, and hair roots. Correlations between protein intake and five variables (serum albumin, red blood cell count, percentage of anagen hairs, protein content per anagen hair root, and anagen bulb diameter) selected as indicators of protein nutriture were studied. Deficient protein intake correlated positively with the protein content of anagenic hair roots. The protein content of anagenic hair roots correlated positively with the serum albumin levels. Protein intake did not correlate with serum albumin level. It is likely that with the relative depletion of protein stores there is impaired synthesis of hair root protein before a decrease in the synthesis of serum albumin which serves a more vital function.", "contents": "Protein status of the elderly as measured by dietary intake, hair tissue, and serum albumin. The nutritional status of 95 Medicare-age individuals was evaluated by dietary intake, physical condition, and components of urine, blood, and hair roots. Correlations between protein intake and five variables (serum albumin, red blood cell count, percentage of anagen hairs, protein content per anagen hair root, and anagen bulb diameter) selected as indicators of protein nutriture were studied. Deficient protein intake correlated positively with the protein content of anagenic hair roots. The protein content of anagenic hair roots correlated positively with the serum albumin levels. Protein intake did not correlate with serum albumin level. It is likely that with the relative depletion of protein stores there is impaired synthesis of hair root protein before a decrease in the synthesis of serum albumin which serves a more vital function."} {"id": "PMID:1266794", "title": "Growth, hemoglobin, cholesterol, and blood pressure observed in rats fed common breakfast cereals.", "content": "Most of the common breakfast cereals tested were unable to support growth or promote health in young rats that consumed these products as their only food. An anemia, accompanied by fatty liver and large concentrations of iron stored in the liver, was observed with cereals having the lowest protein content. Some cereals produced a marked elevation of systolic blood pressure at certain times. Low cholesterol levels were invariably associated with fatty livers, whereas high cholesterol levels seemed to be associated with hypertension at the 45-day period. When only the ready-to-eat cereals were considered, there was a positive correlation between the dietary zinc/copper ratio and the plasma cholesterol concentration.", "contents": "Growth, hemoglobin, cholesterol, and blood pressure observed in rats fed common breakfast cereals. Most of the common breakfast cereals tested were unable to support growth or promote health in young rats that consumed these products as their only food. An anemia, accompanied by fatty liver and large concentrations of iron stored in the liver, was observed with cereals having the lowest protein content. Some cereals produced a marked elevation of systolic blood pressure at certain times. Low cholesterol levels were invariably associated with fatty livers, whereas high cholesterol levels seemed to be associated with hypertension at the 45-day period. When only the ready-to-eat cereals were considered, there was a positive correlation between the dietary zinc/copper ratio and the plasma cholesterol concentration."} {"id": "PMID:1266795", "title": "The carbon pathway for lipogenesis in isolated adipocytes from rat, guinea pig, and human adipose tissue.", "content": "The synthesis of fatty acids from a variety of labeled substrates by isolated adipocytes of the rat, guinea pig, and human was investigated. The incorporation of radioactive glucose and pyruvate into triglyceride fatty acids was considerably lower in human than either rat or guinea pig adipose tissue. By contrast, the incorporation of palmitate into adipose tissue triglycerides was approximately the same in all three species. End carbon analysis of fatty acids isolated from adipocytes incubated with pyruvate-U-14C indicated that although the synthesis of fatty acids in human adipose tissue was extremely low compared to that of the rat and guinea pig, it represented de novo biosynthesis rather than chain elongation of existing fatty acids. It is suggested that in the human, fatty acids are synthetised de novo primarily in the liver. In adipose tissue, lipogenesis consists essentially of the esterification of fatty acids, obtained from plasma, into triglycerides.", "contents": "The carbon pathway for lipogenesis in isolated adipocytes from rat, guinea pig, and human adipose tissue. The synthesis of fatty acids from a variety of labeled substrates by isolated adipocytes of the rat, guinea pig, and human was investigated. The incorporation of radioactive glucose and pyruvate into triglyceride fatty acids was considerably lower in human than either rat or guinea pig adipose tissue. By contrast, the incorporation of palmitate into adipose tissue triglycerides was approximately the same in all three species. End carbon analysis of fatty acids isolated from adipocytes incubated with pyruvate-U-14C indicated that although the synthesis of fatty acids in human adipose tissue was extremely low compared to that of the rat and guinea pig, it represented de novo biosynthesis rather than chain elongation of existing fatty acids. It is suggested that in the human, fatty acids are synthetised de novo primarily in the liver. In adipose tissue, lipogenesis consists essentially of the esterification of fatty acids, obtained from plasma, into triglycerides."} {"id": "PMID:1266796", "title": "Computer simulation of the effects of errors in birth registration on age-dependent anthropometric methods.", "content": "In developing countries birth registration is likely to be delayed, leading to official ages which systematically underestimate the true ages. A computer simulation showed that such official ages underestimate the incidence of malnutrition in a community and lead to misclassification of the nutritional status of many subjects. These errors are more marked below than above 2 years of age. Estimation of the mean delay and its addition to the official ages led to improvement of the results. Above 2 years such estimated ages gave acceptable results; below that age the results were still not acceptable. It is suggested that one method of improving age estimates in large scale anthropometric studies in areas where birth records exist might be to carry out a preliminary survey to estimate the\"mean delay in registration. This mean dealy would be added to all official ages and results above 2 years would be accepted. Below 2 years the estimated birth date would be used as a starting point from which the true birth date can be obtained by careful questioning of the parents. Anthropometric results referred to the ages so obtained would give better results than those of uncorrected ages or age-independent anthropometric methods.", "contents": "Computer simulation of the effects of errors in birth registration on age-dependent anthropometric methods. In developing countries birth registration is likely to be delayed, leading to official ages which systematically underestimate the true ages. A computer simulation showed that such official ages underestimate the incidence of malnutrition in a community and lead to misclassification of the nutritional status of many subjects. These errors are more marked below than above 2 years of age. Estimation of the mean delay and its addition to the official ages led to improvement of the results. Above 2 years such estimated ages gave acceptable results; below that age the results were still not acceptable. It is suggested that one method of improving age estimates in large scale anthropometric studies in areas where birth records exist might be to carry out a preliminary survey to estimate the\"mean delay in registration. This mean dealy would be added to all official ages and results above 2 years would be accepted. Below 2 years the estimated birth date would be used as a starting point from which the true birth date can be obtained by careful questioning of the parents. Anthropometric results referred to the ages so obtained would give better results than those of uncorrected ages or age-independent anthropometric methods."} {"id": "PMID:1266798", "title": "Family planning in a Chinese-American population.", "content": "Among 26 American-born women of Chinese ancestry, 43 Chinese immigrant women who had lived in San Francisco longer than 5 years, and 199 who had immigrated within the last 5 years, fewer than 39% practiced contraception. Oral contraception was used by significantly more of the American-born than of the other two categories of women. Condom or foam was relied upon by sizeable percentages of each immigrant group. Eleven percent of each immigrant group, and 13.3% of the American-born women were sterilized. The only users of an intrauterine device were 3.7% of the immunigrants who had lived in the United States longer than 5 years.", "contents": "Family planning in a Chinese-American population. Among 26 American-born women of Chinese ancestry, 43 Chinese immigrant women who had lived in San Francisco longer than 5 years, and 199 who had immigrated within the last 5 years, fewer than 39% practiced contraception. Oral contraception was used by significantly more of the American-born than of the other two categories of women. Condom or foam was relied upon by sizeable percentages of each immigrant group. Eleven percent of each immigrant group, and 13.3% of the American-born women were sterilized. The only users of an intrauterine device were 3.7% of the immunigrants who had lived in the United States longer than 5 years."} {"id": "PMID:1266799", "title": "The role of Chinese medicine in New York City's Chinatown. 1.", "content": "This study reports on use patterns of traditional Chinese and Western medical resources in New York City's Chinese community. Extensive data from field-work and interview are presented which provide significant new information concerning the health-care attitudes and problems of this unique community.", "contents": "The role of Chinese medicine in New York City's Chinatown. 1. This study reports on use patterns of traditional Chinese and Western medical resources in New York City's Chinese community. Extensive data from field-work and interview are presented which provide significant new information concerning the health-care attitudes and problems of this unique community."} {"id": "PMID:1266800", "title": "Cardiovascular effects of Gardenia florida L. (Gardeniae Fructus) extract.", "content": "Intravenous injection of Gardeniae Fructus extract in rats significantly lowered the systemic arterial pressure which was related to a decreased cardiac output with decreased stroke volume. Gareniae Fructus extract decreased the myocardial contractility of perfused isolated rat heart. Electrocardiogram revealed evidence of myocardial damage and atrioventricular block after a large dose of the extract.", "contents": "Cardiovascular effects of Gardenia florida L. (Gardeniae Fructus) extract. Intravenous injection of Gardeniae Fructus extract in rats significantly lowered the systemic arterial pressure which was related to a decreased cardiac output with decreased stroke volume. Gareniae Fructus extract decreased the myocardial contractility of perfused isolated rat heart. Electrocardiogram revealed evidence of myocardial damage and atrioventricular block after a large dose of the extract."} {"id": "PMID:1266801", "title": "The effects of acupuncture needling on the evoked responses of brain, spinal cord and muscle in man.", "content": "The effects of acupuncture (needling at the Stomach Meridian-36) on the somatosensory evoked responses from the brain (SER), from the spinalcord (EESG) and on the evoked electromy o-gram (EEMG) were studied in normal healthy man. Although amplitude of the early component of the SER was variable during the course of acupuncture and among the subjects, the inhibition of amplitude was seen during and after acupuncture needling. Late components of SER and the negative and positive waves of the EESG showed a high variability during the course of needling and among the subjects. The H-wave amplitude and H/M ratio were also variable, but decreased during and after the needling. The M-wave showed no significant changes. These results suggest that acupuncture reduced the excitability of the specific sensory pathway.", "contents": "The effects of acupuncture needling on the evoked responses of brain, spinal cord and muscle in man. The effects of acupuncture (needling at the Stomach Meridian-36) on the somatosensory evoked responses from the brain (SER), from the spinalcord (EESG) and on the evoked electromy o-gram (EEMG) were studied in normal healthy man. Although amplitude of the early component of the SER was variable during the course of acupuncture and among the subjects, the inhibition of amplitude was seen during and after acupuncture needling. Late components of SER and the negative and positive waves of the EESG showed a high variability during the course of needling and among the subjects. The H-wave amplitude and H/M ratio were also variable, but decreased during and after the needling. The M-wave showed no significant changes. These results suggest that acupuncture reduced the excitability of the specific sensory pathway."} {"id": "PMID:1266802", "title": "Temperature measurements and photoelectric plethysmography in the evaulation of acute and long-term effects of acupuncture upon vasomotor activity of hand skin: a methodological study.", "content": "Skin temperature measurements and photoelectric plethysomgraphy were used evaluating the changes in vasomotor activity of hand skin induced by acupuncture in 8 normal subjects, 10 patients with a chronic pain syndrome and 3 patients with an acute pain syndrome of one upper extremity. In normal persons acupuncture induced short-term fall in the skin temperature and the amplitude of photoelectric plethysmogram. This was undoubtedly a normal physiological reaction to pain. In cold sick hands with a chronic pain syndrome acupuncture induced warming of the hand skin and prolongation of the propagation time in the photoelectric plethysmogram. In warm sick hands with an acute pain syndrome acupuncture induced equalization of the temperature difference and shortening of the propagation time. It seems possible to evaluate the effects of acupuncture upon vasomotor activity of hand skin with these methods.", "contents": "Temperature measurements and photoelectric plethysmography in the evaulation of acute and long-term effects of acupuncture upon vasomotor activity of hand skin: a methodological study. Skin temperature measurements and photoelectric plethysomgraphy were used evaluating the changes in vasomotor activity of hand skin induced by acupuncture in 8 normal subjects, 10 patients with a chronic pain syndrome and 3 patients with an acute pain syndrome of one upper extremity. In normal persons acupuncture induced short-term fall in the skin temperature and the amplitude of photoelectric plethysmogram. This was undoubtedly a normal physiological reaction to pain. In cold sick hands with a chronic pain syndrome acupuncture induced warming of the hand skin and prolongation of the propagation time in the photoelectric plethysmogram. In warm sick hands with an acute pain syndrome acupuncture induced equalization of the temperature difference and shortening of the propagation time. It seems possible to evaluate the effects of acupuncture upon vasomotor activity of hand skin with these methods."} {"id": "PMID:1266803", "title": "D.C. skin conductance variation at acupuncture loci.", "content": "Skin conductance was measured in 10 subjects with a DC Wheatstone bridge in 10 areas purportedly containing acupuncture loci on the Triple Burner (TB) and Lung (Lu) meridians. When the results were compared to those from anatomically similar locations devoid of acupuncture loci, local conductance variation was found to be significantly different (p less than 0.05) in most acupuncture locus locations.", "contents": "D.C. skin conductance variation at acupuncture loci. Skin conductance was measured in 10 subjects with a DC Wheatstone bridge in 10 areas purportedly containing acupuncture loci on the Triple Burner (TB) and Lung (Lu) meridians. When the results were compared to those from anatomically similar locations devoid of acupuncture loci, local conductance variation was found to be significantly different (p less than 0.05) in most acupuncture locus locations."} {"id": "PMID:1266804", "title": "Acupuncture tonification: adjunct in psychiatric rehabilitation.", "content": "Our aim was to \"tonify\" chronic psychiatric patients, i.e., restore their physiological homeostasis and sense of well-being by using standardized acupuncture. In eighteen subjects, eleven diagnosed as schizophrenic, feelings of well-being lasting no longer than three days were obtained in over 60% of the treatments. In more than two-thirds of the cases normalization of blood pressure values tending to 120/80 was evident. Degree of physiological change did not appear to be associated with overall psychological improvement; neither was the number of treatments associated with long-term improvement. For future studies, increased treatment frequency and less rigidly controlled procedures are suggested.", "contents": "Acupuncture tonification: adjunct in psychiatric rehabilitation. Our aim was to \"tonify\" chronic psychiatric patients, i.e., restore their physiological homeostasis and sense of well-being by using standardized acupuncture. In eighteen subjects, eleven diagnosed as schizophrenic, feelings of well-being lasting no longer than three days were obtained in over 60% of the treatments. In more than two-thirds of the cases normalization of blood pressure values tending to 120/80 was evident. Degree of physiological change did not appear to be associated with overall psychological improvement; neither was the number of treatments associated with long-term improvement. For future studies, increased treatment frequency and less rigidly controlled procedures are suggested."} {"id": "PMID:1266805", "title": "Three essential factors in effective acupunture therapy.", "content": "Three essential factors for achieving effective therapeutic results utilizing acupuncture are described: (1) Immune/inflammatory reactions are mobilized when any area of the skin is sufficiently stimulated. (2) Peripheral neural stimulation occurs when specific acupuncture loci are mechanically, electrically, chemically, or thermally activated. Precise stimulation of specific loci (i.e. peripheral neural receptors) may modulate central nervous system regulation of specific physiological functions in the body. (3) Psychological support is well known to be an important factor in all healing experiences, and that includes acupuncture therapy. The authors suggest that the most effective application of acupuncture involves sufficient stimulation of properly selected and precisely localized acupuncture loci combined with a dedicated concern for health that is clearly communicated to patients.", "contents": "Three essential factors in effective acupunture therapy. Three essential factors for achieving effective therapeutic results utilizing acupuncture are described: (1) Immune/inflammatory reactions are mobilized when any area of the skin is sufficiently stimulated. (2) Peripheral neural stimulation occurs when specific acupuncture loci are mechanically, electrically, chemically, or thermally activated. Precise stimulation of specific loci (i.e. peripheral neural receptors) may modulate central nervous system regulation of specific physiological functions in the body. (3) Psychological support is well known to be an important factor in all healing experiences, and that includes acupuncture therapy. The authors suggest that the most effective application of acupuncture involves sufficient stimulation of properly selected and precisely localized acupuncture loci combined with a dedicated concern for health that is clearly communicated to patients."} {"id": "PMID:1266807", "title": "Pathologic findings from the national surgical adjuvant breast project. (Protocol no. 4). III. The significance of extranodal extension of axillary metastases.", "content": "One hundred fifty-eight patients with axillary nodal metastases recovered from radical mastectomy specimens for operable, invasive breast cancer were divided into those in whom such metastases were confined within the node and those in whom one or more nodes manifested extranodal extension. The relationships of these patterns to 33 pathologic and seven clinical features of these cases were investigated by contingency table analysis. Statistically significant associations (p less than .05) between extranodal extension of such metastases and short-term treatment failure, as well as the presence of four or more involved nodes, infiltrating ductal NOS histologic tumor type, stellate tumor border, and nipple involvement, were found. When the metastases were confined to the node there was a significantly greater likelihood that the cancers were either medullary or tubular histologic types. Associations with severe cell reaction and a nuclear grade of 1 were also found, but appeared to reflect the high frequency of medullary carcinomas in this group. The results suggest that evaluation of extranodal extension of axillary nodal metastases in patients with breast cancer may represent an important prognostic discriminant.", "contents": "Pathologic findings from the national surgical adjuvant breast project. (Protocol no. 4). III. The significance of extranodal extension of axillary metastases. One hundred fifty-eight patients with axillary nodal metastases recovered from radical mastectomy specimens for operable, invasive breast cancer were divided into those in whom such metastases were confined within the node and those in whom one or more nodes manifested extranodal extension. The relationships of these patterns to 33 pathologic and seven clinical features of these cases were investigated by contingency table analysis. Statistically significant associations (p less than .05) between extranodal extension of such metastases and short-term treatment failure, as well as the presence of four or more involved nodes, infiltrating ductal NOS histologic tumor type, stellate tumor border, and nipple involvement, were found. When the metastases were confined to the node there was a significantly greater likelihood that the cancers were either medullary or tubular histologic types. Associations with severe cell reaction and a nuclear grade of 1 were also found, but appeared to reflect the high frequency of medullary carcinomas in this group. The results suggest that evaluation of extranodal extension of axillary nodal metastases in patients with breast cancer may represent an important prognostic discriminant."} {"id": "PMID:1266808", "title": "Clindamycin-induced pseudomembranous colitis. Report of three cases.", "content": "Three cases of Clindamycin-induced pseudomembranous colitis are reported. Special attention is focused on histology in the description of the lesions and their recovery in reference with radiologic findings.", "contents": "Clindamycin-induced pseudomembranous colitis. Report of three cases. Three cases of Clindamycin-induced pseudomembranous colitis are reported. Special attention is focused on histology in the description of the lesions and their recovery in reference with radiologic findings."} {"id": "PMID:1266809", "title": "Chediak-Higashi syndrome in a black infant. A light and electron microscopic study with special emphasis on erythrophagocytosis.", "content": "Clinicopathologic observations in the case of a black infant with Chediak-Higashi syndrome are reported. Light and electron microscopic examination of spleen, liver and lymph nodes revealed abnormal large lysosomes as well as marked erythrophagocytosis without hemosiderosis in infiltrating histiocytes and Kupffer cells. In addition, there were abnormal ocular findings. It is suggested that the erythrophagocytosis without hemosiderosis might also be a specific anatomic expression of this disease due to defective lysosomal digestion of phagocytosed erythrocytes.", "contents": "Chediak-Higashi syndrome in a black infant. A light and electron microscopic study with special emphasis on erythrophagocytosis. Clinicopathologic observations in the case of a black infant with Chediak-Higashi syndrome are reported. Light and electron microscopic examination of spleen, liver and lymph nodes revealed abnormal large lysosomes as well as marked erythrophagocytosis without hemosiderosis in infiltrating histiocytes and Kupffer cells. In addition, there were abnormal ocular findings. It is suggested that the erythrophagocytosis without hemosiderosis might also be a specific anatomic expression of this disease due to defective lysosomal digestion of phagocytosed erythrocytes."} {"id": "PMID:1266810", "title": "Congenital hemophagocytic reticulosis.", "content": "A fatal case of an apparently congenital form of hemophagocytic reticulosis is reported. The onset was manifested by hyperbilirubinemia and hepatosplenomegaly which were present at birth and persisted throughout life. Fever, anemia and pancytopenia developed at 1 month of age and became progressively worse. A splenectomy was performed at the age of 3 months, but the child died one day later with disseminated intravascular coagulation and pulmonary hemorrhage. The literature is reviewed with regard to the relationship of this case to (familial) hemophagocytic reticulosis and malignant histiocytosis (histiocytic medullary reticulosis). It is suggested that congenital hemophagocytic reticulosis, as described here, (familial) hemophagocytic reticulosis in infants, and malignant histiocytosis in adults all represent the same basic disorder with different ages of onset and clinicopathologic manifestations.", "contents": "Congenital hemophagocytic reticulosis. A fatal case of an apparently congenital form of hemophagocytic reticulosis is reported. The onset was manifested by hyperbilirubinemia and hepatosplenomegaly which were present at birth and persisted throughout life. Fever, anemia and pancytopenia developed at 1 month of age and became progressively worse. A splenectomy was performed at the age of 3 months, but the child died one day later with disseminated intravascular coagulation and pulmonary hemorrhage. The literature is reviewed with regard to the relationship of this case to (familial) hemophagocytic reticulosis and malignant histiocytosis (histiocytic medullary reticulosis). It is suggested that congenital hemophagocytic reticulosis, as described here, (familial) hemophagocytic reticulosis in infants, and malignant histiocytosis in adults all represent the same basic disorder with different ages of onset and clinicopathologic manifestations."} {"id": "PMID:1266811", "title": "Unusual intravascular material in the brain. Autopsy findings in a patient treated with antihemophilic factor concentrates.", "content": "Widespread vascular occlusion caused by unusual particulate material in the brain of a patient who was intensively treated with antihemophilic factor (AHF) concentrates prior to death is described. The intravascular particles were seen partially or completely occluding both veins and arteries of small caliber in the brain and also to a much lesser extent in other organs. The resultant small focal infarcts were predominantly distributed in the cerebral white matter. The pathogenesis of this apparently unique vascular occlusive phenomenon and its relationship, if any, to the massive AHF concentrate infusion in this patient remain unknown.", "contents": "Unusual intravascular material in the brain. Autopsy findings in a patient treated with antihemophilic factor concentrates. Widespread vascular occlusion caused by unusual particulate material in the brain of a patient who was intensively treated with antihemophilic factor (AHF) concentrates prior to death is described. The intravascular particles were seen partially or completely occluding both veins and arteries of small caliber in the brain and also to a much lesser extent in other organs. The resultant small focal infarcts were predominantly distributed in the cerebral white matter. The pathogenesis of this apparently unique vascular occlusive phenomenon and its relationship, if any, to the massive AHF concentrate infusion in this patient remain unknown."} {"id": "PMID:1266812", "title": "Experimental induction of caprylate-dependent albumin antibodies.", "content": "A normal donor with the caprylate-dependent albumin agglutinins volunteered to receive 50 ml. of 25% caprylate-stabilized human albumin to determine the clinical significance of the antibodies. The donor manifested no clinical sign of a reaction. Samples of blood and urine collected before, during and after administration of albumin were subjected to extensive laboratory investigation. Biochemical, immunologic, hematologic, hemostatic and immunohematologic variables investigated showed only insignificant variations in all blood and urine samples. Results indicated that the infusion of albumin was safe, for the donor showed no sign of a hemolytic, febrile, allergic or anaphylactic transfusion reaction. However, since this is the first and only reported experiment of its kind, it is deemed advisable to exercise caution when administering albumin to patients who have caprylate-dependent albumin agglutinins until sufficient supportive data attesting to the complete safety of this procedure have accumulated.", "contents": "Experimental induction of caprylate-dependent albumin antibodies. A normal donor with the caprylate-dependent albumin agglutinins volunteered to receive 50 ml. of 25% caprylate-stabilized human albumin to determine the clinical significance of the antibodies. The donor manifested no clinical sign of a reaction. Samples of blood and urine collected before, during and after administration of albumin were subjected to extensive laboratory investigation. Biochemical, immunologic, hematologic, hemostatic and immunohematologic variables investigated showed only insignificant variations in all blood and urine samples. Results indicated that the infusion of albumin was safe, for the donor showed no sign of a hemolytic, febrile, allergic or anaphylactic transfusion reaction. However, since this is the first and only reported experiment of its kind, it is deemed advisable to exercise caution when administering albumin to patients who have caprylate-dependent albumin agglutinins until sufficient supportive data attesting to the complete safety of this procedure have accumulated."} {"id": "PMID:1266813", "title": "Critical importance of citrate--blood ratio in platelet aggregation studies.", "content": "The effects of citrate concentration on adenosinediphosphate-, epinephrine-, collagen-, and ristocetin-induced human platelet aggregation were investigated. Relatively small increments in citrate concentration markedly inhibited platelet aggregation by all three physiologic agents. The inhibitory effect was greatest on epinephrine-induced aggregation, and least on collagen-induced aggregation. Ristocetin-induced aggregation was not affected by excess citrate anticoagulation. These findings indicate the importance of controlling the citrate:blood ratio in clinical platelet aggregation studies and in the assessment of antiplatelet drugs.", "contents": "Critical importance of citrate--blood ratio in platelet aggregation studies. The effects of citrate concentration on adenosinediphosphate-, epinephrine-, collagen-, and ristocetin-induced human platelet aggregation were investigated. Relatively small increments in citrate concentration markedly inhibited platelet aggregation by all three physiologic agents. The inhibitory effect was greatest on epinephrine-induced aggregation, and least on collagen-induced aggregation. Ristocetin-induced aggregation was not affected by excess citrate anticoagulation. These findings indicate the importance of controlling the citrate:blood ratio in clinical platelet aggregation studies and in the assessment of antiplatelet drugs."} {"id": "PMID:1266814", "title": "Comparison of a direct latex-agglutination technic with the tanned red cell hemagglutination inhibition immunoassay (TRCHII) for semiquantitation of fibrinogen/fibrin degradation products.", "content": "A new latex-agglutination kit for rapid screening for fibrinogen/fibrin degradation products (FDP/fdp) has been compared with a standard tanned red cell hemagglutination inhibition immunoassay (TRCHII). The latex-agglutination test results agreed with the TRCHII results for 489 of 588 samples (83%). FDP/fdp values were elevated by the latex-agglutination kit when normal by the TRCHII for 79 (13%) samples, and the reverse was true for 20 (3%) samples. Serial dilution of serum sample allowed reliable semiquantitation of FDP/fdp levels compared with TRCHII results (r=less than .001). The latex-agglutination test gave FDP/fdp values of larger than or equal to 10 mug. per ml. for sera from 11 of 13 patients who had acute pulmonary embolism and for only one of 24 normal control samples. The direct latex-agglutination kit for FDP/fdp appears to have appropriate sensitivity to serve as a screening test for acute pulmonary embolism in patients not receiving heparin therapy.", "contents": "Comparison of a direct latex-agglutination technic with the tanned red cell hemagglutination inhibition immunoassay (TRCHII) for semiquantitation of fibrinogen/fibrin degradation products. A new latex-agglutination kit for rapid screening for fibrinogen/fibrin degradation products (FDP/fdp) has been compared with a standard tanned red cell hemagglutination inhibition immunoassay (TRCHII). The latex-agglutination test results agreed with the TRCHII results for 489 of 588 samples (83%). FDP/fdp values were elevated by the latex-agglutination kit when normal by the TRCHII for 79 (13%) samples, and the reverse was true for 20 (3%) samples. Serial dilution of serum sample allowed reliable semiquantitation of FDP/fdp levels compared with TRCHII results (r=less than .001). The latex-agglutination test gave FDP/fdp values of larger than or equal to 10 mug. per ml. for sera from 11 of 13 patients who had acute pulmonary embolism and for only one of 24 normal control samples. The direct latex-agglutination kit for FDP/fdp appears to have appropriate sensitivity to serve as a screening test for acute pulmonary embolism in patients not receiving heparin therapy."} {"id": "PMID:1266815", "title": "Analysis and comparison of two methods to detect hepatitis B antigen. Counterelectrophoresis (CEP) and reversed passive latex-agglutination (RPLA) technic in relationship to radioimmunoassay.", "content": "The authors evaluated two methods for detection of hepatitis B surface antigen, reversed passive latex agglutination and counterelectrophoresis, using radioimmunoassay as a control. The RPLA test (Antigen I, Pfizer Inc., Lot no. 403-94301-1) was compared with radioimmunoassay (RIA, Austria) and counterelectrophoresis (CEP) using serum specimens obtained at the Mount Sinai Medical Center, Miami Beach, Florida. Of the 100 selected sera tested as unknowns, 64 were positive by RIA and 36 were negative. The RPLA test yielded results comparable to those of the RIA technic in that the same 64 positives and 36 negatives identified by RIA were obtained with the RPLA test. Of the 64 positive samples obtained with the RIA technic, five yielded negative results with the CEP method. The RPLA test proved to be more sensitive than CEP in this survey.", "contents": "Analysis and comparison of two methods to detect hepatitis B antigen. Counterelectrophoresis (CEP) and reversed passive latex-agglutination (RPLA) technic in relationship to radioimmunoassay. The authors evaluated two methods for detection of hepatitis B surface antigen, reversed passive latex agglutination and counterelectrophoresis, using radioimmunoassay as a control. The RPLA test (Antigen I, Pfizer Inc., Lot no. 403-94301-1) was compared with radioimmunoassay (RIA, Austria) and counterelectrophoresis (CEP) using serum specimens obtained at the Mount Sinai Medical Center, Miami Beach, Florida. Of the 100 selected sera tested as unknowns, 64 were positive by RIA and 36 were negative. The RPLA test yielded results comparable to those of the RIA technic in that the same 64 positives and 36 negatives identified by RIA were obtained with the RPLA test. Of the 64 positive samples obtained with the RIA technic, five yielded negative results with the CEP method. The RPLA test proved to be more sensitive than CEP in this survey."} {"id": "PMID:1266816", "title": "A previously undescribed gram-negative bacillus causing septicemia and meningitis.", "content": "This report describes a case of septicemia and meningitis secondary to dog bites by two different dogs on two consecutive days. The case is noteworthy because of the unusual characteristics of the etiologic agent and the inability to place the etiologic agent into any currently defined genus or to identify it by the existing systems of classification. The organism is a small, thin, Gram-negative bacillus after 24 hours of incubation on blood agar; after prolonged incubation, it becomes filamentous. The organism is catalase- and oxidase-positive, hydrolyzes esculin, and forms acid in glucose, xylose, and maltose after 21 days' incubation. The organism does not manifest lysis on sheep blood agar, and does not grow on MacConkey, Salmonella-Shigella, Centrimide, nutrient, or Kligler iron agars. The tests for urea, nitrate reduction, and indol are negative. The unidentified Gram-negative bacillus showed susceptibility to all antimicrobials tested except gentamicin.", "contents": "A previously undescribed gram-negative bacillus causing septicemia and meningitis. This report describes a case of septicemia and meningitis secondary to dog bites by two different dogs on two consecutive days. The case is noteworthy because of the unusual characteristics of the etiologic agent and the inability to place the etiologic agent into any currently defined genus or to identify it by the existing systems of classification. The organism is a small, thin, Gram-negative bacillus after 24 hours of incubation on blood agar; after prolonged incubation, it becomes filamentous. The organism is catalase- and oxidase-positive, hydrolyzes esculin, and forms acid in glucose, xylose, and maltose after 21 days' incubation. The organism does not manifest lysis on sheep blood agar, and does not grow on MacConkey, Salmonella-Shigella, Centrimide, nutrient, or Kligler iron agars. The tests for urea, nitrate reduction, and indol are negative. The unidentified Gram-negative bacillus showed susceptibility to all antimicrobials tested except gentamicin."} {"id": "PMID:1266821", "title": "Tuberculous meningitis in childhood. Forty-three cases.", "content": "Forty-three patients in the pediatric age group had tuberculous meningitis. Therapy included the use of adrenocorticosteroids. All four patients who were in stage 1 on admission to the hospital, seven of the 33 in stage 2, and one of the six in stage 3 (coma) recovered without gross neurological sequelas. Eight patients died, and the remaining 23 recovered, with late neurological sequelas. Early diagnosis and appropriate treatment determine the prognosis of tuberculous meningitis.", "contents": "Tuberculous meningitis in childhood. Forty-three cases. Forty-three patients in the pediatric age group had tuberculous meningitis. Therapy included the use of adrenocorticosteroids. All four patients who were in stage 1 on admission to the hospital, seven of the 33 in stage 2, and one of the six in stage 3 (coma) recovered without gross neurological sequelas. Eight patients died, and the remaining 23 recovered, with late neurological sequelas. Early diagnosis and appropriate treatment determine the prognosis of tuberculous meningitis."} {"id": "PMID:1266822", "title": "Factors in the initiation of bicycle-motor vehicle collisions.", "content": "In this study, 888 injury-producing bicycle-motor vehicle collisions were examined. On the basis of the movements of the vehicles involved, the bicyclist or the bicycle or both was probably responsible for the initiation of more than three fourths of the collisions. Bicyclist age was strongly related to probable responsibility for the collision. Through age 12, nine out of ten bicyclists were probably responsible for the collision; above age 12, probable responsibility decreased in proportion to age; and only 34% of the bicyclists aged 25 years or older were probably responsible. Collisions involving bicyclists in various age groups differed considerably in where, when, and how they occurred. The movements of the vehicles primarily involved in the initiation of the collisions were evaluated in terms of counter-measure planning.", "contents": "Factors in the initiation of bicycle-motor vehicle collisions. In this study, 888 injury-producing bicycle-motor vehicle collisions were examined. On the basis of the movements of the vehicles involved, the bicyclist or the bicycle or both was probably responsible for the initiation of more than three fourths of the collisions. Bicyclist age was strongly related to probable responsibility for the collision. Through age 12, nine out of ten bicyclists were probably responsible for the collision; above age 12, probable responsibility decreased in proportion to age; and only 34% of the bicyclists aged 25 years or older were probably responsible. Collisions involving bicyclists in various age groups differed considerably in where, when, and how they occurred. The movements of the vehicles primarily involved in the initiation of the collisions were evaluated in terms of counter-measure planning."} {"id": "PMID:1266823", "title": "Wide sutures and large fontanels in the newborn.", "content": "Newborn infants with wide cranial sutures and large anterior fontanels, but having normal head circumferences, were prospectively studied and compared with a group of normal controls. The study group with wide sutures was composed of two different groups--one with good calcification of the calvaria, fairly large anterior fontanels, and no Wormian bones; and another with distinct parietal prominences, very large anterior and posterior fontanels with prolonged patency, poor initial calcification of the calvaria, and Wormian bones. Normal head growth and physical and mental development were observed in all the infants studied.", "contents": "Wide sutures and large fontanels in the newborn. Newborn infants with wide cranial sutures and large anterior fontanels, but having normal head circumferences, were prospectively studied and compared with a group of normal controls. The study group with wide sutures was composed of two different groups--one with good calcification of the calvaria, fairly large anterior fontanels, and no Wormian bones; and another with distinct parietal prominences, very large anterior and posterior fontanels with prolonged patency, poor initial calcification of the calvaria, and Wormian bones. Normal head growth and physical and mental development were observed in all the infants studied."} {"id": "PMID:1266824", "title": "DDT levels in milk of rural indigent blacks.", "content": "Human milk samples from low-income blacks residing in rural Mississippi and Arkansas and middle-class whites residing in metropolitan Nashville, Tenn, were analyzed for concentrations of DDT and its metabolites. The mean total DDT concentration (DDE [derivative of DDT]+DDT) of 38 samples from the blacks was 447 parts per billion (ppb); the range was 59 to 1,900 ppb. The mean of the 14 samples from Nashville residents was 75 ppb (range, 15 to 133 ppb). The difference in the DDT concentrations in the two populations indicates that rural low-income blacks are still highly contaminated with pesticides, even though the general use of DDT has been banned. Due to the limited amount of information from the donors, no correlation could be made between the DDT concentration and diet, age of child, home pesticide use, or distance of residence from farming fields.", "contents": "DDT levels in milk of rural indigent blacks. Human milk samples from low-income blacks residing in rural Mississippi and Arkansas and middle-class whites residing in metropolitan Nashville, Tenn, were analyzed for concentrations of DDT and its metabolites. The mean total DDT concentration (DDE [derivative of DDT]+DDT) of 38 samples from the blacks was 447 parts per billion (ppb); the range was 59 to 1,900 ppb. The mean of the 14 samples from Nashville residents was 75 ppb (range, 15 to 133 ppb). The difference in the DDT concentrations in the two populations indicates that rural low-income blacks are still highly contaminated with pesticides, even though the general use of DDT has been banned. Due to the limited amount of information from the donors, no correlation could be made between the DDT concentration and diet, age of child, home pesticide use, or distance of residence from farming fields."} {"id": "PMID:1266825", "title": "Cognitive stimulation.", "content": "Cross-sectional studies suggest that the intellectual development of American children is affected by experiences in the first three years of life. Furthermore, Piaget and White have observed and documented direct effects of the environment on the development of infants during the first year of life. Principles derived from animal research and the disappointing results of preschool intervention programs highlight the irreversible nature of early infant-environment interaction. Future programs designed to prevent educational incapacitation among children must concentrate on optimizing the developmental milieu of the child before he is 4 years old. Accomplishing this task is the practical challenge in the field of child development today.", "contents": "Cognitive stimulation. Cross-sectional studies suggest that the intellectual development of American children is affected by experiences in the first three years of life. Furthermore, Piaget and White have observed and documented direct effects of the environment on the development of infants during the first year of life. Principles derived from animal research and the disappointing results of preschool intervention programs highlight the irreversible nature of early infant-environment interaction. Future programs designed to prevent educational incapacitation among children must concentrate on optimizing the developmental milieu of the child before he is 4 years old. Accomplishing this task is the practical challenge in the field of child development today."} {"id": "PMID:1266828", "title": "Accidental digitoxin poisoning.", "content": "A healthy 141/2-month-old child ingested 1.5 mg of digitoxin by accident. Digitoxin was wrongly identified as digoxin, the initial electrocardiogram was misinterpreted, and the vomiting was underestimated as an important symptom of toxicity. Symptoms persisted and the patient was hospitalized. Serial digitoxin levels were obtained and correlated with ECG and clinical course. It appears that serial digitoxin levels can be a useful adjunct in diagnosis, assessment of severity, and indication of recovery from digitoxin poisoning. In each patient, it is imperative that ECG, pharmacologic, and clinical indicators of digitalis toxicity be accurately identified for proper assessment of severity and appropriate management.", "contents": "Accidental digitoxin poisoning. A healthy 141/2-month-old child ingested 1.5 mg of digitoxin by accident. Digitoxin was wrongly identified as digoxin, the initial electrocardiogram was misinterpreted, and the vomiting was underestimated as an important symptom of toxicity. Symptoms persisted and the patient was hospitalized. Serial digitoxin levels were obtained and correlated with ECG and clinical course. It appears that serial digitoxin levels can be a useful adjunct in diagnosis, assessment of severity, and indication of recovery from digitoxin poisoning. In each patient, it is imperative that ECG, pharmacologic, and clinical indicators of digitalis toxicity be accurately identified for proper assessment of severity and appropriate management."} {"id": "PMID:1266829", "title": "Recurrent arterial thrombosis in nephrosis.", "content": "Recurrent arterial thrombosis without inciting trauma occurred in an 8-year-old boy with the nephrotic syndrome. Thrombosis of the left femoral artery was successfully managed by early thrombectomy and postoperative anticoagulation therapy, but the right leg finally had to be amputated. The development of hypovolemia in the nephrotic child receiving long-term steroid therapy apparently increases the tendency to a hypercoagulable state.", "contents": "Recurrent arterial thrombosis in nephrosis. Recurrent arterial thrombosis without inciting trauma occurred in an 8-year-old boy with the nephrotic syndrome. Thrombosis of the left femoral artery was successfully managed by early thrombectomy and postoperative anticoagulation therapy, but the right leg finally had to be amputated. The development of hypovolemia in the nephrotic child receiving long-term steroid therapy apparently increases the tendency to a hypercoagulable state."} {"id": "PMID:1266830", "title": "Epidermodysplasia verruciformis.", "content": "Epidermodysplasia verruciformis (EV) is characterized by the early onset of extensive, persistent verruca plana that may undergo malignant transformation. Immunologic studies of a case of EV confirmed by electron microscopic identification of the virus disclosed no detectable abnormalities. The importance of this uncommon clinical syndrome lies in its demonstration that benign papovavirus, the etiologic agent of warts, can produce malignant neoplasms in genetically susceptible hosts.", "contents": "Epidermodysplasia verruciformis. Epidermodysplasia verruciformis (EV) is characterized by the early onset of extensive, persistent verruca plana that may undergo malignant transformation. Immunologic studies of a case of EV confirmed by electron microscopic identification of the virus disclosed no detectable abnormalities. The importance of this uncommon clinical syndrome lies in its demonstration that benign papovavirus, the etiologic agent of warts, can produce malignant neoplasms in genetically susceptible hosts."} {"id": "PMID:1266831", "title": "Familial imperforate anus.", "content": "A boy, 2 years 5 months of age, was admitted for examination and was found to be mentally retarded. He had a history of low birth weight, covered anus, and perineal fistula. Investigation revealed ventricular septal defect and persistent left superior vena cava, left upper lobe atelectasis, hand and foot anomalies, agenesis or nonfunctioning right kidney and large left kidney with double pelves and double ureters, and large sigmoid colon. Family history revealed consanguineous parents and a mentally retarded elder sister who had anorectal atresia with introital fistula and perineal ectopic stenotic anus. This family demonstrates two extremes of the same syndrome, most probably inherited as an autosomal-recessive entity.", "contents": "Familial imperforate anus. A boy, 2 years 5 months of age, was admitted for examination and was found to be mentally retarded. He had a history of low birth weight, covered anus, and perineal fistula. Investigation revealed ventricular septal defect and persistent left superior vena cava, left upper lobe atelectasis, hand and foot anomalies, agenesis or nonfunctioning right kidney and large left kidney with double pelves and double ureters, and large sigmoid colon. Family history revealed consanguineous parents and a mentally retarded elder sister who had anorectal atresia with introital fistula and perineal ectopic stenotic anus. This family demonstrates two extremes of the same syndrome, most probably inherited as an autosomal-recessive entity."} {"id": "PMID:1266835", "title": "Bile salts and bioelectric properties of rat jejunum.", "content": "Addition of conjugated bile salts increased transmural- and transserosal-potential differences of sheets of rat jejunum. Removal of Cl- from buffer solutions minimized the bile-sale induced bioelectric changes. Bile-salt induced doubling of tissue resistance was not explained by an observed increase in net Cl- serosa leads to mucosa flux. Electrical effects were unrelated to concentration and were observed only when bile-salt solutions perfused the jejunal mucosa. The molecular events associated with bile-salt interactions with the plasma membrane affecting ion fluxes may relate to their unique effects on sterol absorption.", "contents": "Bile salts and bioelectric properties of rat jejunum. Addition of conjugated bile salts increased transmural- and transserosal-potential differences of sheets of rat jejunum. Removal of Cl- from buffer solutions minimized the bile-sale induced bioelectric changes. Bile-salt induced doubling of tissue resistance was not explained by an observed increase in net Cl- serosa leads to mucosa flux. Electrical effects were unrelated to concentration and were observed only when bile-salt solutions perfused the jejunal mucosa. The molecular events associated with bile-salt interactions with the plasma membrane affecting ion fluxes may relate to their unique effects on sterol absorption."} {"id": "PMID:1266836", "title": "Therapy with gastrin antibody in the Zollinger-Ellison syndrome.", "content": "The therapeutic effectiveness of parenterally administered rabbit antigastrin antibody was evaluated in a patient with the Zollinger-Ellison syndrome who had a fasting serum gastrin level of 3020 pg/ml and a basal gastric acid secretion of 48.9 mEq/hr. Control globulin reduced gastric secretion to 32 mEq/hr. Gastrin antibody reduced it futher to 8.7 mEq/hr. Betazole hydrochloride which was given 75 min after administration of gastrin antibody stimulated acid secretion to 57.2 mEq/hr. One day later basal acid secretion was uninhibited although some antibody activity was present in the patient's serum. The results suggested that gastrin antibody acutely inhibited basal but not betazole-stimulated secretion.", "contents": "Therapy with gastrin antibody in the Zollinger-Ellison syndrome. The therapeutic effectiveness of parenterally administered rabbit antigastrin antibody was evaluated in a patient with the Zollinger-Ellison syndrome who had a fasting serum gastrin level of 3020 pg/ml and a basal gastric acid secretion of 48.9 mEq/hr. Control globulin reduced gastric secretion to 32 mEq/hr. Gastrin antibody reduced it futher to 8.7 mEq/hr. Betazole hydrochloride which was given 75 min after administration of gastrin antibody stimulated acid secretion to 57.2 mEq/hr. One day later basal acid secretion was uninhibited although some antibody activity was present in the patient's serum. The results suggested that gastrin antibody acutely inhibited basal but not betazole-stimulated secretion."} {"id": "PMID:1266838", "title": "Liver-lung scan in the diagnosis of right subphrenic abscess.", "content": "To assess the value of liver-lung scanning in the diagnosis of right subphrenic abscess, 148 scans were reviewed against corresponding charts. Of 91 scans with adequate clinical data, overall scanning error was 19.3% with 14 false positive and 3 false negative scans. Among 49 scans (of the initial group of 91 studies) with presence or absence of actual pathology proved by surgery and/or autopsy, there were 3 true positive, 12 false positive, 29 true negative, and 3 false negative scans. Analysis of data indicated (1) lower accuracy of scan interpretations than generally reported, (2) low specificity for positive scans and high specificity for negative scans, (3) correlations of false interpretations with atypical degrees of liver-lung separation and with scanning defects in liver and lung, and (4) failure of rereading significantly to improve accuracy of interpretation.", "contents": "Liver-lung scan in the diagnosis of right subphrenic abscess. To assess the value of liver-lung scanning in the diagnosis of right subphrenic abscess, 148 scans were reviewed against corresponding charts. Of 91 scans with adequate clinical data, overall scanning error was 19.3% with 14 false positive and 3 false negative scans. Among 49 scans (of the initial group of 91 studies) with presence or absence of actual pathology proved by surgery and/or autopsy, there were 3 true positive, 12 false positive, 29 true negative, and 3 false negative scans. Analysis of data indicated (1) lower accuracy of scan interpretations than generally reported, (2) low specificity for positive scans and high specificity for negative scans, (3) correlations of false interpretations with atypical degrees of liver-lung separation and with scanning defects in liver and lung, and (4) failure of rereading significantly to improve accuracy of interpretation."} {"id": "PMID:1266839", "title": "Pyloric-sphincter studies in peptic-ulcer patients: pylorus in peptic ulcer.", "content": "Pyloric pressure was assayed by a manometric procedure in the basal state and after intraduodenal infusion of HCl. 13 control subjects, 11 patients with benign gastric ulcer, 8 with duodenal ulcer, and 2 with coexistent gastric and duodenal ulcers were studied. Mean resting pyloric pressure in gastric-ulcer patients (5.17 +/- 0.71) mm Hg) was significantly lower than controls (9.40 +/- 0.85 mm Hg) and did not increase after HCl perfusion into the duodenum. Mean basal pyloric pressure in duodenal-ulcer patients (11.30 +/- 1.57 mm Hg) did not differ significantly from controls and increased after intraduodenal perfusion of HCl to 15.72 +/- 2.40 mm Hg. The two patients with coexistent ulcers had manometric patterns similar to gastric-ulcer patients. Decreased pyloric-sphincter pressure in gastric-ulcer patients may be the mechanism responsible for the increased duodeno-gastric reflux observed in these patients.", "contents": "Pyloric-sphincter studies in peptic-ulcer patients: pylorus in peptic ulcer. Pyloric pressure was assayed by a manometric procedure in the basal state and after intraduodenal infusion of HCl. 13 control subjects, 11 patients with benign gastric ulcer, 8 with duodenal ulcer, and 2 with coexistent gastric and duodenal ulcers were studied. Mean resting pyloric pressure in gastric-ulcer patients (5.17 +/- 0.71) mm Hg) was significantly lower than controls (9.40 +/- 0.85 mm Hg) and did not increase after HCl perfusion into the duodenum. Mean basal pyloric pressure in duodenal-ulcer patients (11.30 +/- 1.57 mm Hg) did not differ significantly from controls and increased after intraduodenal perfusion of HCl to 15.72 +/- 2.40 mm Hg. The two patients with coexistent ulcers had manometric patterns similar to gastric-ulcer patients. Decreased pyloric-sphincter pressure in gastric-ulcer patients may be the mechanism responsible for the increased duodeno-gastric reflux observed in these patients."} {"id": "PMID:1266840", "title": "A functional description of the canine choledochoduodenal flutter valve.", "content": "Forward- and reverse-opening pressures of the choledochoduodenal junction were measured in anesthetized, vagotomized dogs. Mean reverse-opening pressures were found to be significantly greater in most cases including those following the intraductal administration of vasoactive agents which are known to significantly influence mean forward-opening pressures. The polypeptides CCK-PZ and CCK-C8 were ineffective in reducing mean forward-opening pressures regardless of the route of administration. Previously published observations have indicated that mean forward-opening pressures are also unaffected by nervous activity. It is concluded that the canine choledochoduodenal junction possesses the physical and functional properties of a passive flutter valve during duodenal relaxation.", "contents": "A functional description of the canine choledochoduodenal flutter valve. Forward- and reverse-opening pressures of the choledochoduodenal junction were measured in anesthetized, vagotomized dogs. Mean reverse-opening pressures were found to be significantly greater in most cases including those following the intraductal administration of vasoactive agents which are known to significantly influence mean forward-opening pressures. The polypeptides CCK-PZ and CCK-C8 were ineffective in reducing mean forward-opening pressures regardless of the route of administration. Previously published observations have indicated that mean forward-opening pressures are also unaffected by nervous activity. It is concluded that the canine choledochoduodenal junction possesses the physical and functional properties of a passive flutter valve during duodenal relaxation."} {"id": "PMID:1266841", "title": "Prognostic value of spontaneous hyponatremia in cirrhosis with ascites.", "content": "Spontaneous hyponatremia in cirrhosis with ascites is generally considered to be due to an impaired renal ability to excrete free water, to be a contraindication of diuretics, and to be a bad prognostic sign. These concepts are reviewed in this paper. 55 cirrhotics with ascites were divided into three groups. Group I consisted of 13 patients with hyponatremia and very low free-water clearance CH2O, 0.07 +/- 0.26 ml/min). These patients also had poor renal function: low inulin clearance (CINU, 40.6 +/- 25.9 ml/min) and paraaminohippurate clearance (CPAH, 383 +/- 275 ml/min). Group II consisted of 8 patients who also had hyponatremia. CH2O, CINU, and CPAH in these patients were fairly high: 5.85 +/- 1.53 ml/min, 85.7 +/- 26.2 ml/min, and 651 +/- 294 ml/min. These values are similar to those o7 +/- 4.27 ml/min, 94.7 +/- 33.1 ml/min, and 598 +/- 199 ml/min. Hyponatremia in Group I could be related to the impaired free-water clearance. The mechanism of hyponatremia in Group II patients is not clear. Patients with hyponatremia and low CINU and CPAH had a negative response to diuretics and a poor prognosis. Patients with hyponatremia but with relatively good renal function had a good prognosis, similar to Group III patients. They responded to diuretics with no worsening of their hyponatremia.", "contents": "Prognostic value of spontaneous hyponatremia in cirrhosis with ascites. Spontaneous hyponatremia in cirrhosis with ascites is generally considered to be due to an impaired renal ability to excrete free water, to be a contraindication of diuretics, and to be a bad prognostic sign. These concepts are reviewed in this paper. 55 cirrhotics with ascites were divided into three groups. Group I consisted of 13 patients with hyponatremia and very low free-water clearance CH2O, 0.07 +/- 0.26 ml/min). These patients also had poor renal function: low inulin clearance (CINU, 40.6 +/- 25.9 ml/min) and paraaminohippurate clearance (CPAH, 383 +/- 275 ml/min). Group II consisted of 8 patients who also had hyponatremia. CH2O, CINU, and CPAH in these patients were fairly high: 5.85 +/- 1.53 ml/min, 85.7 +/- 26.2 ml/min, and 651 +/- 294 ml/min. These values are similar to those o7 +/- 4.27 ml/min, 94.7 +/- 33.1 ml/min, and 598 +/- 199 ml/min. Hyponatremia in Group I could be related to the impaired free-water clearance. The mechanism of hyponatremia in Group II patients is not clear. Patients with hyponatremia and low CINU and CPAH had a negative response to diuretics and a poor prognosis. Patients with hyponatremia but with relatively good renal function had a good prognosis, similar to Group III patients. They responded to diuretics with no worsening of their hyponatremia."} {"id": "PMID:1266842", "title": "Intramural barium in ischemic colitis: a new radiographic finding.", "content": "Two cases of ischemic colitis are presented, demonstrating a new radiographic finding of intramural dissection of barium. Colonoscopic findings were compatible with that diagnosis. Deep, discrete ulcerations were observed during the healing process. Both patients recovered and prolonged retention of the intramural barium was seen.", "contents": "Intramural barium in ischemic colitis: a new radiographic finding. Two cases of ischemic colitis are presented, demonstrating a new radiographic finding of intramural dissection of barium. Colonoscopic findings were compatible with that diagnosis. Deep, discrete ulcerations were observed during the healing process. Both patients recovered and prolonged retention of the intramural barium was seen."} {"id": "PMID:1266843", "title": "Endoscopic retrograde pancreatography: analysis of the normal pancreatogram.", "content": "Thirty-five pancreatograms were selected from 62 which were obtained during endoscopic cannulation of the papilla of Vater with retrograde injection of radiopaque medium. Pancreatograms were selected on the basis of the quality of the study and on the absence of any clinically demonstrable pancreatic disease. Measurements were made of the main pancreatic duct (MPD) in the head, body, and tail, as well as the length of the duct. Although there is a wide range of normal, practical reference figures for the diameters of the main duct in the head, body, and tail are 3, 2 and 1 mm, respectively. The length averages 15.4 cm. No correlation was found between the measurements and the body surface area, age, or sex of the patient. Comparisons are made with other autopsy and endoscopic studies, and attention is focused on the salient anatomic features, including normal points of narrowing of the duct, the accessory pancreatic duct (APD), and the main pancreatic duct branches (MPDB).", "contents": "Endoscopic retrograde pancreatography: analysis of the normal pancreatogram. Thirty-five pancreatograms were selected from 62 which were obtained during endoscopic cannulation of the papilla of Vater with retrograde injection of radiopaque medium. Pancreatograms were selected on the basis of the quality of the study and on the absence of any clinically demonstrable pancreatic disease. Measurements were made of the main pancreatic duct (MPD) in the head, body, and tail, as well as the length of the duct. Although there is a wide range of normal, practical reference figures for the diameters of the main duct in the head, body, and tail are 3, 2 and 1 mm, respectively. The length averages 15.4 cm. No correlation was found between the measurements and the body surface area, age, or sex of the patient. Comparisons are made with other autopsy and endoscopic studies, and attention is focused on the salient anatomic features, including normal points of narrowing of the duct, the accessory pancreatic duct (APD), and the main pancreatic duct branches (MPDB)."} {"id": "PMID:1266847", "title": "The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease.", "content": "In a population at equilibrium for a sex-linked lethal, one-third of the genes for that lethal must arise anew each generation. Therefore, one-third of all cases of Lesch-Nyhan disease, a severe X-linked recessive lethal disorder, should be new mutants. To test this hypothesis, we have collected 47 families, 20 with a single proband and 27 with multiple affected males in which the patients' mothers and other female relatives had been studied for heterozygosity. Available carrier detection tests identify heterozygous for HPRT deficiency in hair roots and skin fibroblasts. Only four mothers were found not to be carriers. This result deviates significantly from expected (P less than .001). Statistical tests for ascertainment effects indicated absence of bias for multiple proband families but strong bias in favor of families with many heterozygous females. When the analysis was limited to single proband families, the deviation from expected was still significant (P less than .01). The incidence of new mutants among the heterozygous mothers, as determined by the ratio of +/+ to +/- maternal grandmothers, should be one-half (see Appendix). Of all 20 maternal grandmothers studied, five were +/+ and 15 were +/- (P less than .05). Considering only the single proband families, the ratio of 5 +/+ to 8 +/- was not significantly different from expected. In four of the five cases in which the heterozygous mother of an affected individual was a new mutation, the age of her parents was considerably higher than the mean parental age in the population. This raises the possibility of a paternal age effect on X-linked mutations. There appears to be a true deficiency of new mutatnts among males but not among females. Data on additional Lesch-Nyhan families are needed before conclusions regarding a possible higher mutation rate in males can be drawn.", "contents": "The occurrence of new mutants in the X-linked recessive Lesch-Nyhan disease. In a population at equilibrium for a sex-linked lethal, one-third of the genes for that lethal must arise anew each generation. Therefore, one-third of all cases of Lesch-Nyhan disease, a severe X-linked recessive lethal disorder, should be new mutants. To test this hypothesis, we have collected 47 families, 20 with a single proband and 27 with multiple affected males in which the patients' mothers and other female relatives had been studied for heterozygosity. Available carrier detection tests identify heterozygous for HPRT deficiency in hair roots and skin fibroblasts. Only four mothers were found not to be carriers. This result deviates significantly from expected (P less than .001). Statistical tests for ascertainment effects indicated absence of bias for multiple proband families but strong bias in favor of families with many heterozygous females. When the analysis was limited to single proband families, the deviation from expected was still significant (P less than .01). The incidence of new mutants among the heterozygous mothers, as determined by the ratio of +/+ to +/- maternal grandmothers, should be one-half (see Appendix). Of all 20 maternal grandmothers studied, five were +/+ and 15 were +/- (P less than .05). Considering only the single proband families, the ratio of 5 +/+ to 8 +/- was not significantly different from expected. In four of the five cases in which the heterozygous mother of an affected individual was a new mutation, the age of her parents was considerably higher than the mean parental age in the population. This raises the possibility of a paternal age effect on X-linked mutations. There appears to be a true deficiency of new mutatnts among males but not among females. Data on additional Lesch-Nyhan families are needed before conclusions regarding a possible higher mutation rate in males can be drawn."} {"id": "PMID:1266848", "title": "Application of the lod method to the detection of linkage between a quantitative trait and a qualitative marker: a simulation experiment.", "content": "Simulation experiments were performed to assess the power of the lod method for detecting linkage between a quantitative trait and a qualitative marker. Using family data on the Amy2-Duffy linkage, it was found that linkage detection is feasible in certain limited circumstances. The same qualitative data yielded no evidence for a significant difference in male and female recombination fractions.", "contents": "Application of the lod method to the detection of linkage between a quantitative trait and a qualitative marker: a simulation experiment. Simulation experiments were performed to assess the power of the lod method for detecting linkage between a quantitative trait and a qualitative marker. Using family data on the Amy2-Duffy linkage, it was found that linkage detection is feasible in certain limited circumstances. The same qualitative data yielded no evidence for a significant difference in male and female recombination fractions."} {"id": "PMID:1266850", "title": "Analysis of deoxyribonucleic acid replication in human X chromosomes by fluorescence microscopy.", "content": "The genetically inactive, late-replicating human female X chromosome can be effectively distinguished from its more active, earlier-replicating homologue, when cells are grown according to the appropriate BrdU-33258 Hoechst protocol. Results obtained from a fluorescence analysis of DNA replication in X chromosomes are consistent with those from previous autoradiographic studies, but reflect additional sensitivity and resolution offered by the BrdU-Hoechst methodology. Both qualitative and quantitative differences in 33258 Hoechst fluorescence intensity, reflecting alterations in replication kinetics, can be detected between the two X chromosomes in female cells. The pattern of replication in the single X chromosome in male cells is indistinguishable from that of the early female X. Intercellular fluctuations in the distribution of regions replicating early or late in S phase, particularly with reference to the late female X, can be localized to structural bands, suggesting multifocal control of DNA synthesis in X chromosomes.", "contents": "Analysis of deoxyribonucleic acid replication in human X chromosomes by fluorescence microscopy. The genetically inactive, late-replicating human female X chromosome can be effectively distinguished from its more active, earlier-replicating homologue, when cells are grown according to the appropriate BrdU-33258 Hoechst protocol. Results obtained from a fluorescence analysis of DNA replication in X chromosomes are consistent with those from previous autoradiographic studies, but reflect additional sensitivity and resolution offered by the BrdU-Hoechst methodology. Both qualitative and quantitative differences in 33258 Hoechst fluorescence intensity, reflecting alterations in replication kinetics, can be detected between the two X chromosomes in female cells. The pattern of replication in the single X chromosome in male cells is indistinguishable from that of the early female X. Intercellular fluctuations in the distribution of regions replicating early or late in S phase, particularly with reference to the late female X, can be localized to structural bands, suggesting multifocal control of DNA synthesis in X chromosomes."} {"id": "PMID:1266851", "title": "The karaite community of Iraq in Israel: a genetic study.", "content": "Ninety-eight of 136 (72%) individuals at least 6 years of age from a small isolate of the Karaite community, known to have lived in Iraq since the tenth century, were examined. In Iraq this group maintained a highly inbred existence but married Karaites from Egypt after their immigration to Israel in 1951. Observations of several unique gene frequencies for blood group and isoenzyme markers, not described among other Jewish groups, are explicable by isolation and genetic drift in a very small community.", "contents": "The karaite community of Iraq in Israel: a genetic study. Ninety-eight of 136 (72%) individuals at least 6 years of age from a small isolate of the Karaite community, known to have lived in Iraq since the tenth century, were examined. In Iraq this group maintained a highly inbred existence but married Karaites from Egypt after their immigration to Israel in 1951. Observations of several unique gene frequencies for blood group and isoenzyme markers, not described among other Jewish groups, are explicable by isolation and genetic drift in a very small community."} {"id": "PMID:1266852", "title": "A third type of serum cholinesterase deficiency in Eskimos.", "content": "A new type of serum cholinesterase deficiency with less than 10% of the normal activity was found in an Alaskan Eskimo. The new type of deficiency appeared to be allelic with two types previously described in this population.", "contents": "A third type of serum cholinesterase deficiency in Eskimos. A new type of serum cholinesterase deficiency with less than 10% of the normal activity was found in an Alaskan Eskimo. The new type of deficiency appeared to be allelic with two types previously described in this population."} {"id": "PMID:1266853", "title": "Esterase D in South American Indians.", "content": "Significant variation in the frequency of Esterase D isoenzymes was found in 1,070 individuals belonging to eight South American Indian tribes. The Es D1 allele shows frequencies varying from .36 to 1. A region of low prevalence of this allele seems to exist in northern Brazil, involving the Parakanan, Gorotire, and Krah\u00f3. The intratribal variation observed in eight Yanomama villages located in Brazil was not exceptional.", "contents": "Esterase D in South American Indians. Significant variation in the frequency of Esterase D isoenzymes was found in 1,070 individuals belonging to eight South American Indian tribes. The Es D1 allele shows frequencies varying from .36 to 1. A region of low prevalence of this allele seems to exist in northern Brazil, involving the Parakanan, Gorotire, and Krah\u00f3. The intratribal variation observed in eight Yanomama villages located in Brazil was not exceptional."} {"id": "PMID:1266854", "title": "The frequency of \"rare\" protein variants in Marshall islanders and other Micronesians.", "content": "Blood specimens from a sample of 373 Marshall Islanders were studied with reference to variants of 23 serum proteins and erythrocyte enzymes. Six of the traits studied exhibited genetic polymorphisms (adenosine deaminase, phosphoglucomutase1, acid phosphatase, 6-phosphogluconate dehydrogenase, haptoglobin, and group specific component). There were in addition four \"rare\" variants (albumin, transferrin, lactate dehydrogenase, and galactose-1-phosphate uridylyltransferase) involving nine persons, among 8,503 determinations. The frequency of rare variants in Micronesians was compared with the frequencies in West European Caucasians and Amerindians. There are many difficulties in such comparisons, and although the observed values for the three ethnic groups differ by a factor of three (the Micronesians exhibiting the lowest frequency), it is felt that no firm conclusions concerning differences between ethnic groups can be drawn at this time.", "contents": "The frequency of \"rare\" protein variants in Marshall islanders and other Micronesians. Blood specimens from a sample of 373 Marshall Islanders were studied with reference to variants of 23 serum proteins and erythrocyte enzymes. Six of the traits studied exhibited genetic polymorphisms (adenosine deaminase, phosphoglucomutase1, acid phosphatase, 6-phosphogluconate dehydrogenase, haptoglobin, and group specific component). There were in addition four \"rare\" variants (albumin, transferrin, lactate dehydrogenase, and galactose-1-phosphate uridylyltransferase) involving nine persons, among 8,503 determinations. The frequency of rare variants in Micronesians was compared with the frequencies in West European Caucasians and Amerindians. There are many difficulties in such comparisons, and although the observed values for the three ethnic groups differ by a factor of three (the Micronesians exhibiting the lowest frequency), it is felt that no firm conclusions concerning differences between ethnic groups can be drawn at this time."} {"id": "PMID:1266855", "title": "The inheritance of fingerprint patterns.", "content": "Analysis of the fingerprints of 571 members of the Habbanite isolate suggest inherited patterns and pattern sequences. A genetic theory has been developed; it assumes that the basic fingerprint pattern sequence is all ulnar loops and that a variety of genes cause deviations from this pattern sequence. Genes that have been proposed include: (1) a semidominant gene for whorls on the thumbs (one homozygote has whorls on both thumbs, the other has ulnar loops on both thumbs and the heterozygote usually has two ulnar loops or one ulnar loop and one whorl); (2) a semidominant gene for whorls on the ring fingers which acts like the gene for whorls on the thumbs; (3) a dominant gene for arches on the thumbs and often on other fingers; (4) one or more dominant genes for arches on the fingers; (5) a dominant gene for whorls on all fingers except for an ulnar loop on the middle finger; (6) a dominant gene for radial loops on the index fingers, frequently associated with an arch on the middle fingers; and (7) a recessive gene for radial loops on the ring and little fingers. These genes may act independently or may show epistasis.", "contents": "The inheritance of fingerprint patterns. Analysis of the fingerprints of 571 members of the Habbanite isolate suggest inherited patterns and pattern sequences. A genetic theory has been developed; it assumes that the basic fingerprint pattern sequence is all ulnar loops and that a variety of genes cause deviations from this pattern sequence. Genes that have been proposed include: (1) a semidominant gene for whorls on the thumbs (one homozygote has whorls on both thumbs, the other has ulnar loops on both thumbs and the heterozygote usually has two ulnar loops or one ulnar loop and one whorl); (2) a semidominant gene for whorls on the ring fingers which acts like the gene for whorls on the thumbs; (3) a dominant gene for arches on the thumbs and often on other fingers; (4) one or more dominant genes for arches on the fingers; (5) a dominant gene for whorls on all fingers except for an ulnar loop on the middle finger; (6) a dominant gene for radial loops on the index fingers, frequently associated with an arch on the middle fingers; and (7) a recessive gene for radial loops on the ring and little fingers. These genes may act independently or may show epistasis."} {"id": "PMID:1266865", "title": "Pharmacy personnel activities and costs in decentralized and centralized unit dose drug distribution systems.", "content": "Pharmacy personnel activities and labor costs directly associated with concurrent decentralized and centralized unit dose drug distribution systems in the same institution were compared. A work-sampling observation technique was used for the activity survey. Analysis of the data showed that: (1) the activities of pharmacy personnel vary significantly between the decentralized and centralized systems, (2) pharmacists in the decentralized area spent a significantly greater portion of their productive time performing therapy-related activities than did those pharmacists in the centralized system, (3) multiple staffing patterns associated with the centralized unit dose system afforded a significantly greater participation in educational activities by all pharmacy personnel staffing that area, (4) dispensing activities accounted for most nonpharmacist personnel time in both systems, and (5) based on cost/unit dose and existing staffing patterns, there was no appreciable difference in personnel labor costs associated with the two systems. However, it was determined that a considerable cost difference could be expected if the decentralized system's hours of service were equivalent to those associated with the centralized system.", "contents": "Pharmacy personnel activities and costs in decentralized and centralized unit dose drug distribution systems. Pharmacy personnel activities and labor costs directly associated with concurrent decentralized and centralized unit dose drug distribution systems in the same institution were compared. A work-sampling observation technique was used for the activity survey. Analysis of the data showed that: (1) the activities of pharmacy personnel vary significantly between the decentralized and centralized systems, (2) pharmacists in the decentralized area spent a significantly greater portion of their productive time performing therapy-related activities than did those pharmacists in the centralized system, (3) multiple staffing patterns associated with the centralized unit dose system afforded a significantly greater participation in educational activities by all pharmacy personnel staffing that area, (4) dispensing activities accounted for most nonpharmacist personnel time in both systems, and (5) based on cost/unit dose and existing staffing patterns, there was no appreciable difference in personnel labor costs associated with the two systems. However, it was determined that a considerable cost difference could be expected if the decentralized system's hours of service were equivalent to those associated with the centralized system."} {"id": "PMID:1266866", "title": "Digoxin tablets--a review of the bioavailability problems.", "content": "A review is presented of the more significant aspects of recent bioavailability studies on digoxin tablets that have led to the identification of variations among commercially available tablets and of the correlation of the methods commonly used in such bioavailability evaluations. Pharmacopeial requirements for tablet-to-tablet uniformity of content do not automatically yield uniformity of bioavailability. In vitro dissolution rate of digoxin tablets generally has been shown to correlate with in vivo bioavailability, and this has led to new governmental and pharmacopeial requirements for digoxin tablets. However, some recent reports have shown that in vitro dissolution rate may not always correlate well with bioavailability. The relevance and significance of digoxin tablet bioavailability to clinical effects and therapeutics are briefly discussed.", "contents": "Digoxin tablets--a review of the bioavailability problems. A review is presented of the more significant aspects of recent bioavailability studies on digoxin tablets that have led to the identification of variations among commercially available tablets and of the correlation of the methods commonly used in such bioavailability evaluations. Pharmacopeial requirements for tablet-to-tablet uniformity of content do not automatically yield uniformity of bioavailability. In vitro dissolution rate of digoxin tablets generally has been shown to correlate with in vivo bioavailability, and this has led to new governmental and pharmacopeial requirements for digoxin tablets. However, some recent reports have shown that in vitro dissolution rate may not always correlate well with bioavailability. The relevance and significance of digoxin tablet bioavailability to clinical effects and therapeutics are briefly discussed."} {"id": "PMID:1266867", "title": "Nursing attitudes toward oral liquid unit dose packaging.", "content": "Nurses' attitudes toward three types of oral liquid unit dose packages--glass, plastic and aluminum--were determined. Thirty nurses who previously had not used unit dose packaging on their units were asked to evaluate the three types of packaging. The nurses preferred both aluminum and plastic over the glass containers; there was no significant difference in attitude toward the plastic and aluminum packages.", "contents": "Nursing attitudes toward oral liquid unit dose packaging. Nurses' attitudes toward three types of oral liquid unit dose packages--glass, plastic and aluminum--were determined. Thirty nurses who previously had not used unit dose packaging on their units were asked to evaluate the three types of packaging. The nurses preferred both aluminum and plastic over the glass containers; there was no significant difference in attitude toward the plastic and aluminum packages."} {"id": "PMID:1266868", "title": "Unit dose radiopharmaceutical service as a component of total pharmacy practice.", "content": "A unit dose radiopharmaceutical distribution system as a component of total pharmacy services is discussed. The radiopharmacy functions of compounding, calibrating and distributing are rotated on a weekly basis among the staff pharmacists. The elution process and departmental policies and procedures are described. The pharmacist's unique expertise for preparing radiopharmaceutical doses is discussed.", "contents": "Unit dose radiopharmaceutical service as a component of total pharmacy practice. A unit dose radiopharmaceutical distribution system as a component of total pharmacy services is discussed. The radiopharmacy functions of compounding, calibrating and distributing are rotated on a weekly basis among the staff pharmacists. The elution process and departmental policies and procedures are described. The pharmacist's unique expertise for preparing radiopharmaceutical doses is discussed."} {"id": "PMID:1266869", "title": "Evaluation of drugs by the medical letter.", "content": "The operation of The Medical Letter on Drugs and Therapeutics, a biweekly newsletter on drug evaluations for physicians and other health personnel, is described. Included are a discussion of the history and current organization of the publication, method of writing reports, financing, and relations with the pharmaceutical industry. The future of The Medical Letter, in light of more stringent FDA procedures and the fewer new drugs being marketed, is discussed also.", "contents": "Evaluation of drugs by the medical letter. The operation of The Medical Letter on Drugs and Therapeutics, a biweekly newsletter on drug evaluations for physicians and other health personnel, is described. Included are a discussion of the history and current organization of the publication, method of writing reports, financing, and relations with the pharmaceutical industry. The future of The Medical Letter, in light of more stringent FDA procedures and the fewer new drugs being marketed, is discussed also."} {"id": "PMID:1266877", "title": "Improved pharmacy services through pharmacist participation in medical rounds.", "content": "The participation by pharmacists in medical rounds in a 250-bed pediatric hospital with centralized unit dose drug distribution and i.v. admixture programs is discussed. A redistribution of responsibilities enabled pharmacists to attend physician work rounds on each medical service. Nursing-pharmacy rounds were set up for services which had no scheduled physician work rounds. As a result, the amount of medication waste due to late order changes, which had previously been a problem, was reduced by 0.54 cents per patient day. Pharmacist participation in medical rounds increased his clinical expertise and supplied him with the clinical data necessary to make more informed recommendations to physicians.", "contents": "Improved pharmacy services through pharmacist participation in medical rounds. The participation by pharmacists in medical rounds in a 250-bed pediatric hospital with centralized unit dose drug distribution and i.v. admixture programs is discussed. A redistribution of responsibilities enabled pharmacists to attend physician work rounds on each medical service. Nursing-pharmacy rounds were set up for services which had no scheduled physician work rounds. As a result, the amount of medication waste due to late order changes, which had previously been a problem, was reduced by 0.54 cents per patient day. Pharmacist participation in medical rounds increased his clinical expertise and supplied him with the clinical data necessary to make more informed recommendations to physicians."} {"id": "PMID:1266878", "title": "Motivation of the hospital pharmacist.", "content": "Some theories of how management can motivate employees to perform effectively, and the application of these theories to hospital pharmacy practice, are discussed. Types of extrinsic and intrinsic rewards and how they can best be allocated to encourage greater productivity are described. Management must be consistent and credible in its reward allocations in order to maintain the expectation of employees that increased effort will result in rewards. It is important also that management ascertains what employees interpret as desirable rewards.", "contents": "Motivation of the hospital pharmacist. Some theories of how management can motivate employees to perform effectively, and the application of these theories to hospital pharmacy practice, are discussed. Types of extrinsic and intrinsic rewards and how they can best be allocated to encourage greater productivity are described. Management must be consistent and credible in its reward allocations in order to maintain the expectation of employees that increased effort will result in rewards. It is important also that management ascertains what employees interpret as desirable rewards."} {"id": "PMID:1266879", "title": "Effect of hyperthyroidism on hypoprothrombinemic response to warfarin.", "content": "Clinical observations and studies regarding hyperthyroidism and enhanced response to warfarin are reviewed. The reported cases of increased sensitivity to warfarin in hyperthyroidism are summarized, and possible mechanisms for this disease-drug interaction are discussed. Most recent studies indicate that the activity of warfarin is enhanced in hyperthyroidism because of increased catabolism of vitamin-K-dependent clotting factors.", "contents": "Effect of hyperthyroidism on hypoprothrombinemic response to warfarin. Clinical observations and studies regarding hyperthyroidism and enhanced response to warfarin are reviewed. The reported cases of increased sensitivity to warfarin in hyperthyroidism are summarized, and possible mechanisms for this disease-drug interaction are discussed. Most recent studies indicate that the activity of warfarin is enhanced in hyperthyroidism because of increased catabolism of vitamin-K-dependent clotting factors."} {"id": "PMID:1266880", "title": "Novel method for the determination of pediatric dosages.", "content": "A method by which safe and effective pediatric dosages can be estimated is presented. The method is based on the facts that drugs distribute into body water compartments and that these compartments are significantly different between pediatric and adult populations. The method discussed is tested using data reported in the literature.", "contents": "Novel method for the determination of pediatric dosages. A method by which safe and effective pediatric dosages can be estimated is presented. The method is based on the facts that drugs distribute into body water compartments and that these compartments are significantly different between pediatric and adult populations. The method discussed is tested using data reported in the literature."} {"id": "PMID:1266881", "title": "Gas-solid chromatography of isopropyl alcohol samples.", "content": "A study was conducted to analyze the accuracy of the procedure used by a hospital pharmacy to make solutions of 70% isopropyl alcohol and to determine the amount of evaporation of the alcohol which may take place when the containers of these solutions are repeatedly opened. Twenty-five samples of 70% isopropyl alcohol were obtained from eight hospital wards. All the containers had been in patient care areas for over one month and were less than one-half full. Six of the samples were randomly chosen for gas-chromatographic analysis. The results show that gas chromatography for the quantitative analysis of isopropyl alcohol is highly reliable and suitable for the analysis of very large or very small samples. There was no significant amount of evaporation of isopropyl alcohol despite the length of time the solutions had been on the hospital wards.", "contents": "Gas-solid chromatography of isopropyl alcohol samples. A study was conducted to analyze the accuracy of the procedure used by a hospital pharmacy to make solutions of 70% isopropyl alcohol and to determine the amount of evaporation of the alcohol which may take place when the containers of these solutions are repeatedly opened. Twenty-five samples of 70% isopropyl alcohol were obtained from eight hospital wards. All the containers had been in patient care areas for over one month and were less than one-half full. Six of the samples were randomly chosen for gas-chromatographic analysis. The results show that gas chromatography for the quantitative analysis of isopropyl alcohol is highly reliable and suitable for the analysis of very large or very small samples. There was no significant amount of evaporation of isopropyl alcohol despite the length of time the solutions had been on the hospital wards."} {"id": "PMID:1266882", "title": "A modified ortho-toluidine reagent for glucose analysis.", "content": "A micromethod for the determination of glucose using a modified ortho-toluidine reagent is described. The proposed method correlates well with the original o-toluidine method. The reaction follows Beer's Law over a wide range of concentrations. The modified reagent contains 75 per cent less glacial acetic acid than the original ortho-toluidine reagent. The color intensity of the Schiff's base is two to three times higher than the original reagent.", "contents": "A modified ortho-toluidine reagent for glucose analysis. A micromethod for the determination of glucose using a modified ortho-toluidine reagent is described. The proposed method correlates well with the original o-toluidine method. The reaction follows Beer's Law over a wide range of concentrations. The modified reagent contains 75 per cent less glacial acetic acid than the original ortho-toluidine reagent. The color intensity of the Schiff's base is two to three times higher than the original reagent."} {"id": "PMID:1266883", "title": "Antimicrobial susceptibility testing of anaerobic bacteria.", "content": "Antimicrobial therapy of anaerobic infections is usually predicted on the basis of known patterns of susceptibility of anaerobic bacteria to antimicrobial agents rather than on results of in vitro tests of individual isolates. Routine susceptibility testing of anaerobic bacteria is not recommended, but there are instances of serious infection, i.e., endocarditis, or specific infecting organisms, e.g., Bacteroides fragilis, when in vitro testing of the specific infecting organism is indicated. No standard method has yet been accepted. Methods presently recommended are agar dilution or broth dilution tests. Other methods currently being evaluated are agar (disc) diffusion, broth-disc, and simplified broth and agar dilution tests. The advantages and limitations of the various methods are discussed.", "contents": "Antimicrobial susceptibility testing of anaerobic bacteria. Antimicrobial therapy of anaerobic infections is usually predicted on the basis of known patterns of susceptibility of anaerobic bacteria to antimicrobial agents rather than on results of in vitro tests of individual isolates. Routine susceptibility testing of anaerobic bacteria is not recommended, but there are instances of serious infection, i.e., endocarditis, or specific infecting organisms, e.g., Bacteroides fragilis, when in vitro testing of the specific infecting organism is indicated. No standard method has yet been accepted. Methods presently recommended are agar dilution or broth dilution tests. Other methods currently being evaluated are agar (disc) diffusion, broth-disc, and simplified broth and agar dilution tests. The advantages and limitations of the various methods are discussed."} {"id": "PMID:1266884", "title": "Retraining of inactive medical technologists - Whose responsibility?", "content": "A survey was conducted to determine if inactive female medical technologists wish to reactivate, what degree of retraining they feel necessary to do so, and their willingness to pay for such experience. A corollary purpose was to determine the need for inactive technologists, the hiring practices employed, the existence of institutionally sponsored retraining programs, and the institutional views toward providing such programs. Findings revealed that inactive medical technologists wish to return to the field, feel the need for retraining, would prefer a hospital retraining site, and are willing to pay for their retraining. Institutions expressed a need for inactive medical technologists but are most willing to hire individuals who have been retrained. A plentiful supply of new graduates effectively negates this preference in the more densely populated areas. Hospitals and universities are varied in their opinions as to who should provide retraining programs. Few have instituted retraining programs due to high expense and limited availability of financing.", "contents": "Retraining of inactive medical technologists - Whose responsibility? A survey was conducted to determine if inactive female medical technologists wish to reactivate, what degree of retraining they feel necessary to do so, and their willingness to pay for such experience. A corollary purpose was to determine the need for inactive technologists, the hiring practices employed, the existence of institutionally sponsored retraining programs, and the institutional views toward providing such programs. Findings revealed that inactive medical technologists wish to return to the field, feel the need for retraining, would prefer a hospital retraining site, and are willing to pay for their retraining. Institutions expressed a need for inactive medical technologists but are most willing to hire individuals who have been retrained. A plentiful supply of new graduates effectively negates this preference in the more densely populated areas. Hospitals and universities are varied in their opinions as to who should provide retraining programs. Few have instituted retraining programs due to high expense and limited availability of financing."} {"id": "PMID:1266885", "title": "Contract method of individualized instruction applied to clinical bacteriology.", "content": "An experiment using individualized instruction in clinical bacteriology in a medical technology hospital program is described. Individualized instruction is reviewed as well as the Duluth contract method which was used. The results of this experiment were favorable and the study concludes that students would profit if individualized instruction were used in a medical technology clinical program.", "contents": "Contract method of individualized instruction applied to clinical bacteriology. An experiment using individualized instruction in clinical bacteriology in a medical technology hospital program is described. Individualized instruction is reviewed as well as the Duluth contract method which was used. The results of this experiment were favorable and the study concludes that students would profit if individualized instruction were used in a medical technology clinical program."} {"id": "PMID:1266886", "title": "A ventilation system for processing areas in histopathology laboratories.", "content": "A ventilation system designed for use in our tissue processing laboratory at the National Center for Toxicological Research is illustrated. To facilitate the large volume of research tissue processed daily for our histology labs we use ten Autotechnicon Ultras that process a total of 100 mice daily. This number of tissue processors presents a problem of adequate ventilation.", "contents": "A ventilation system for processing areas in histopathology laboratories. A ventilation system designed for use in our tissue processing laboratory at the National Center for Toxicological Research is illustrated. To facilitate the large volume of research tissue processed daily for our histology labs we use ten Autotechnicon Ultras that process a total of 100 mice daily. This number of tissue processors presents a problem of adequate ventilation."} {"id": "PMID:1266887", "title": "Serum viscosity and hyperviscosity syndrome in IGG multiple myeloma - the relationship of Sia test and to concentration of M component.", "content": "The Sia test has been used for a long time for the diagnosis of macroglobulinemia, but its significance in myeloma is not known. It has recently been reported that the majority of sera in immunoglobulin G (IgG) myeloma with hyperviscosity syndrome are Sia-positive.", "contents": "Serum viscosity and hyperviscosity syndrome in IGG multiple myeloma - the relationship of Sia test and to concentration of M component. The Sia test has been used for a long time for the diagnosis of macroglobulinemia, but its significance in myeloma is not known. It has recently been reported that the majority of sera in immunoglobulin G (IgG) myeloma with hyperviscosity syndrome are Sia-positive."} {"id": "PMID:1266888", "title": "Delayed hemostatic changes following cardiopulmonary bypass.", "content": "A variety of hemostatic abnormalities has been reported in patients following open-heart surgery. Since surgery itself may induce changes in the coagulation system, the analyses of postoperative coagulation assays in the bleeding patients may be extremely difficult to interpret without an understanding of the coagulation dynamics in the nonhemorrhagic postoperative patients. Thus, we studied the pattern of change in several coagulation assays performed on 36 consecutive patients before and during the first two postoperative weeks. Approximately one third of the patients has some clotting abnormality before surgery. Shortened prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed within the first three postoperative days. Only following warfarin therapy (initiated on the third postoperative day) was significant prolongation of PT and APTT observed. During the 14 postoperative days, fibrinogen levels and fibrinogen degradation products progressively increased without prolongation of the thrombin time or decrease in the euglobulin clot lysis time. On the first postoperative day, the platelet count and platelet adhesiveness values were significantly less than before surgery (p less than 0.01 and p less than 0.05). Over the following two weeks, the platelet count and platelet adhesiveness returned to normal. Although there was slight lengthening of the Ivy bleeding time on the first postoperative day, this assay was never abnormal. Thus, we conclude that the following cardiopulmonary bypass there is (1) probably activation of circulating procoagulants, (2) progressive increase in fibrinogen levels, (3) activation to the fibrinolytic system, and (4) transient thrombocytopenia with a superimposed platelet defect.", "contents": "Delayed hemostatic changes following cardiopulmonary bypass. A variety of hemostatic abnormalities has been reported in patients following open-heart surgery. Since surgery itself may induce changes in the coagulation system, the analyses of postoperative coagulation assays in the bleeding patients may be extremely difficult to interpret without an understanding of the coagulation dynamics in the nonhemorrhagic postoperative patients. Thus, we studied the pattern of change in several coagulation assays performed on 36 consecutive patients before and during the first two postoperative weeks. Approximately one third of the patients has some clotting abnormality before surgery. Shortened prothrombin time (PT) and activated partial thromboplastin time (APTT) were observed within the first three postoperative days. Only following warfarin therapy (initiated on the third postoperative day) was significant prolongation of PT and APTT observed. During the 14 postoperative days, fibrinogen levels and fibrinogen degradation products progressively increased without prolongation of the thrombin time or decrease in the euglobulin clot lysis time. On the first postoperative day, the platelet count and platelet adhesiveness values were significantly less than before surgery (p less than 0.01 and p less than 0.05). Over the following two weeks, the platelet count and platelet adhesiveness returned to normal. Although there was slight lengthening of the Ivy bleeding time on the first postoperative day, this assay was never abnormal. Thus, we conclude that the following cardiopulmonary bypass there is (1) probably activation of circulating procoagulants, (2) progressive increase in fibrinogen levels, (3) activation to the fibrinolytic system, and (4) transient thrombocytopenia with a superimposed platelet defect."} {"id": "PMID:1266889", "title": "Early diagnosis of vulnerability in cancer patients.", "content": "The newly diagnosed CA patient faces psychosocial as well as physical problems. To assess the impact of diagnosis, and to find significant clues for later emotional distress, 163 new patients with CA of the breast, colon, lung, Hodgkin's disease, and malignant melanoma were evaluated by interviews, psychological testing, and personality inventories, then followed regularly for six months. Vulnerability was but one parameter that measured emotional distress and faltering capacity to cope with concurrent problems. It was found that the more vulnerable patients had more symptoms when first diagnosed, and that systemic symptoms were more significant than the type of CA or the staging. High vulnerability patients were generally pessimistic, anticipating little recovery and practically no support from significant others. They had more marital problems, tended to suppress feelings, but often had a history of depression. Denial in itself did not mean vulnerability. Indecision about treatment and regrets about the past were more indicative of future emotional problems than was delay. Most patients showed little denial throughout the period of observation, but more vulnerable patients tended to vacillate between denial and acceptance. By learning to listen and ask tactful questions, this information can be elicited by the physician who can then intervene effectively.", "contents": "Early diagnosis of vulnerability in cancer patients. The newly diagnosed CA patient faces psychosocial as well as physical problems. To assess the impact of diagnosis, and to find significant clues for later emotional distress, 163 new patients with CA of the breast, colon, lung, Hodgkin's disease, and malignant melanoma were evaluated by interviews, psychological testing, and personality inventories, then followed regularly for six months. Vulnerability was but one parameter that measured emotional distress and faltering capacity to cope with concurrent problems. It was found that the more vulnerable patients had more symptoms when first diagnosed, and that systemic symptoms were more significant than the type of CA or the staging. High vulnerability patients were generally pessimistic, anticipating little recovery and practically no support from significant others. They had more marital problems, tended to suppress feelings, but often had a history of depression. Denial in itself did not mean vulnerability. Indecision about treatment and regrets about the past were more indicative of future emotional problems than was delay. Most patients showed little denial throughout the period of observation, but more vulnerable patients tended to vacillate between denial and acceptance. By learning to listen and ask tactful questions, this information can be elicited by the physician who can then intervene effectively."} {"id": "PMID:1266890", "title": "Characteristics of bacterial endocarditis in heroin addicts in Detroit.", "content": "Over 24 months (January 1972-December 1973) 48 intravenous heroin users were admitted to Detroit General Hospital with 50 episodes of bacterial endocarditis (B.E.). Staphylococcus aureus (25 cases), enterococci (13 cases), and Pseudomonas aeruginosa (5 cases) were the usual pathogens, accounting for 86 per cent of these illnesses. Occasional episodes were due to other streptococci or diphtheroids which were susceptible to penicillin G. Staphylococcal and pseudomonas endocarditis usually involved the tricuspid valve, while enterococci affected aortic or mitral valves. Pre-existing valvular heart disease was not the sole determinant of the site of infection.", "contents": "Characteristics of bacterial endocarditis in heroin addicts in Detroit. Over 24 months (January 1972-December 1973) 48 intravenous heroin users were admitted to Detroit General Hospital with 50 episodes of bacterial endocarditis (B.E.). Staphylococcus aureus (25 cases), enterococci (13 cases), and Pseudomonas aeruginosa (5 cases) were the usual pathogens, accounting for 86 per cent of these illnesses. Occasional episodes were due to other streptococci or diphtheroids which were susceptible to penicillin G. Staphylococcal and pseudomonas endocarditis usually involved the tricuspid valve, while enterococci affected aortic or mitral valves. Pre-existing valvular heart disease was not the sole determinant of the site of infection."} {"id": "PMID:1266891", "title": "Aortic regurgitation and pigmentation - unusual features of Noonan syndrome.", "content": "A patient with typical features of Noonan's syndrome showed aortic regurgitation and widespread diffuse hyperpigmentation, features not previously associated with this syndrome. Detailed endocrine and dermatological studies failed to delineate the cause of hyperpigmentation. In addition to mild aortic regurgitation, cardiac catheterization revealed mild left ventricular dysfunction, probably due to primary myocardial disease. Other interesting findings included lymphedema and sexual infantilism despite normal testosterone levels.", "contents": "Aortic regurgitation and pigmentation - unusual features of Noonan syndrome. A patient with typical features of Noonan's syndrome showed aortic regurgitation and widespread diffuse hyperpigmentation, features not previously associated with this syndrome. Detailed endocrine and dermatological studies failed to delineate the cause of hyperpigmentation. In addition to mild aortic regurgitation, cardiac catheterization revealed mild left ventricular dysfunction, probably due to primary myocardial disease. Other interesting findings included lymphedema and sexual infantilism despite normal testosterone levels."} {"id": "PMID:1266895", "title": "Drug addiction in pregnancy and the neonate.", "content": "Drug addiction during pregnancy has been managed in two ways: the detoxification program and the methadone-maintenance treatment program. In the detoxification program, there have been few complications for the mother and child except for low birth weight, meconium-stained amniotic fluid, and an increase in breech presentation. The methadone-maintenance treatment program at this time is the most satisfactory approach to the treatment of heroin addiction. The complications of pregnancy in this program are similar to those of the average obstetric population. Low birth weight at term is still frequent for those on methadone maintenance. The problem of multiple drug abuse, including heroin, cocaine, alcohol, tranquilizers, and amphetamines, requires more attention. The characteristics of the withdrawal syndrome and its treatment in infants are described. Excessive weight loss and irritability are commin in these infants. Of the many drugs available for the treatment of the newborn withdrawal syndrome, diazepam is currently favored. The long-term effects of intrauterine drug exposure, the withdrawal syndrome, and treatment are generally unknown. Schedules for management of adult narcotic, alcohol, and barbiturate abuse and newborn narcotic withdrawal are suggested.", "contents": "Drug addiction in pregnancy and the neonate. Drug addiction during pregnancy has been managed in two ways: the detoxification program and the methadone-maintenance treatment program. In the detoxification program, there have been few complications for the mother and child except for low birth weight, meconium-stained amniotic fluid, and an increase in breech presentation. The methadone-maintenance treatment program at this time is the most satisfactory approach to the treatment of heroin addiction. The complications of pregnancy in this program are similar to those of the average obstetric population. Low birth weight at term is still frequent for those on methadone maintenance. The problem of multiple drug abuse, including heroin, cocaine, alcohol, tranquilizers, and amphetamines, requires more attention. The characteristics of the withdrawal syndrome and its treatment in infants are described. Excessive weight loss and irritability are commin in these infants. Of the many drugs available for the treatment of the newborn withdrawal syndrome, diazepam is currently favored. The long-term effects of intrauterine drug exposure, the withdrawal syndrome, and treatment are generally unknown. Schedules for management of adult narcotic, alcohol, and barbiturate abuse and newborn narcotic withdrawal are suggested."} {"id": "PMID:1266896", "title": "Conization as only treatment of carcinoma in situ of the uterine cervix.", "content": "Knife conization was performed in 2,099 cases with abnormal vaginal smears. The frequency of complications was low. Carcinoma in situ was diagnosed in 1,500 cases and follow-up showed that conization was curative in 87%. The curative rate was depending on whether the resection margins were free of pathologic epithelium or not. If smears were repeatedly negative the first year after conization a new diagnosis of cancer was made in 0.4%. It was not possible to decide whether these lesions were residual changes or true recurrences. Treatment of carcinoma in situ by conization has so far reduced the frequency of invasive cervical cancer by 60%.", "contents": "Conization as only treatment of carcinoma in situ of the uterine cervix. Knife conization was performed in 2,099 cases with abnormal vaginal smears. The frequency of complications was low. Carcinoma in situ was diagnosed in 1,500 cases and follow-up showed that conization was curative in 87%. The curative rate was depending on whether the resection margins were free of pathologic epithelium or not. If smears were repeatedly negative the first year after conization a new diagnosis of cancer was made in 0.4%. It was not possible to decide whether these lesions were residual changes or true recurrences. Treatment of carcinoma in situ by conization has so far reduced the frequency of invasive cervical cancer by 60%."} {"id": "PMID:1266897", "title": "Ultrastructural studies on the endometrium of women wearing TCu-200 intrauterine devices by means of transmission and scanning electron microscopy and x-ray dispersive analysis.", "content": "Endometrial biopsies obtained from 12 young women wearing TCu-200 intrauterine contraceptive devices from six to 12 months were studied by means of transmission and scanning electron microscopes as well as with the use of rubeanic acid stains and x-ray dispersive analysis. Six biopsies were taken at Day 10 and six were taken at Day 20 of the menstrual cycle. The aim was to investigate epithelial and stromal changes possibly related to copper deposition. The main changes were located in the cell organelles at Day 10 of the cycle. The mitochondria disclosed vacuolization of the matrix and myelin figure formation in 70 to 80% of the epithelial cells. There were also increased numbers of lysosomes. There were similar alterations of secretory endometrium in only a few cases. Instead, there was an increased number of mitochondria, and most of them were dividing. Rubeanic acid stains as well as energy-dispersive x-ray analysis failed to reveal significant amounts of copper in the various cell organelles studied. The above observations seem to indicate that there is a definite alteration of the mitochondria of epithelial cells which may result in impairment of respiratory mechanisms and energy production, rendering the endometrial environment inhospitable to the fertilized egg. These changes are thought to be reversible. The absence of copper is explained on the basis of a rapid turnover of the endometrium or to a problem in sampling common to this methodology.", "contents": "Ultrastructural studies on the endometrium of women wearing TCu-200 intrauterine devices by means of transmission and scanning electron microscopy and x-ray dispersive analysis. Endometrial biopsies obtained from 12 young women wearing TCu-200 intrauterine contraceptive devices from six to 12 months were studied by means of transmission and scanning electron microscopes as well as with the use of rubeanic acid stains and x-ray dispersive analysis. Six biopsies were taken at Day 10 and six were taken at Day 20 of the menstrual cycle. The aim was to investigate epithelial and stromal changes possibly related to copper deposition. The main changes were located in the cell organelles at Day 10 of the cycle. The mitochondria disclosed vacuolization of the matrix and myelin figure formation in 70 to 80% of the epithelial cells. There were also increased numbers of lysosomes. There were similar alterations of secretory endometrium in only a few cases. Instead, there was an increased number of mitochondria, and most of them were dividing. Rubeanic acid stains as well as energy-dispersive x-ray analysis failed to reveal significant amounts of copper in the various cell organelles studied. The above observations seem to indicate that there is a definite alteration of the mitochondria of epithelial cells which may result in impairment of respiratory mechanisms and energy production, rendering the endometrial environment inhospitable to the fertilized egg. These changes are thought to be reversible. The absence of copper is explained on the basis of a rapid turnover of the endometrium or to a problem in sampling common to this methodology."} {"id": "PMID:1266893", "title": "Familial dextrocardia, divergent strabismus and situs inversus of optic disc.", "content": "A family is described in which three of four siblings have major congenital cardiac defects in association with ocular abnormalities. The eldest sibling has isolated dextrocardia and the second has total situs inversus. The fourth child has both atrial and ventricular septal defects, with pulmonary hypertension and right ventricular hypertrophy. The mother and third sibling have normal hearts but exhibit a number of ocular defects. The principal ocular anomalies demonstrated in this family are divergent strabismus, bilateral situs inversus of the optic disc, and myopia. The hereditary aspect of these multiple findings is discussed.", "contents": "Familial dextrocardia, divergent strabismus and situs inversus of optic disc. A family is described in which three of four siblings have major congenital cardiac defects in association with ocular abnormalities. The eldest sibling has isolated dextrocardia and the second has total situs inversus. The fourth child has both atrial and ventricular septal defects, with pulmonary hypertension and right ventricular hypertrophy. The mother and third sibling have normal hearts but exhibit a number of ocular defects. The principal ocular anomalies demonstrated in this family are divergent strabismus, bilateral situs inversus of the optic disc, and myopia. The hereditary aspect of these multiple findings is discussed."} {"id": "PMID:1266898", "title": "The effect of meperidine analgesia on midtrimester abortions induced with intra-amniotic prostaglandin F2alpha.", "content": "To determine whether increased amounts of meperidine significantly affect the induction of abortion with intra-amniotic prostaglandin F2alpha, 42 midtrimester subjects were treated with an identical dose schedule of PFG2alpha and one of two dose schedules of meperidine. Although the group that received more mepridine reported severe pain less frequently, their mean and median induction-to-abortion times, cumulative abortion rate, uterine contractility, and complications were not significantly different from those of the group that received less meperidine.", "contents": "The effect of meperidine analgesia on midtrimester abortions induced with intra-amniotic prostaglandin F2alpha. To determine whether increased amounts of meperidine significantly affect the induction of abortion with intra-amniotic prostaglandin F2alpha, 42 midtrimester subjects were treated with an identical dose schedule of PFG2alpha and one of two dose schedules of meperidine. Although the group that received more mepridine reported severe pain less frequently, their mean and median induction-to-abortion times, cumulative abortion rate, uterine contractility, and complications were not significantly different from those of the group that received less meperidine."} {"id": "PMID:1266894", "title": "A case of Buerger's disease causing ischemic colitis with perforation in a young male.", "content": "A case of Bueger's disease causing ischemic colitis with perforation in a 32-year-old male is presented. Abdominal angiography demonstrated occlusion of the vasculature supplying the involved transverse colon. The association of Buerger's disease with ischemic colitis is emphasized.", "contents": "A case of Buerger's disease causing ischemic colitis with perforation in a young male. A case of Bueger's disease causing ischemic colitis with perforation in a 32-year-old male is presented. Abdominal angiography demonstrated occlusion of the vasculature supplying the involved transverse colon. The association of Buerger's disease with ischemic colitis is emphasized."} {"id": "PMID:1266899", "title": "Perinatal vitamin D metabolism. III. Factors influencing late gestational human serum 25-hydroxyvitamin D.", "content": "Sera were obtained during the last trimester from both black and white women receiving prenatal care for determinations of calcium, magnesium, and 25-hydroxyvitamin D (25-OHD). The mean serum 25-OHD concentrations were 15.4 +/- 5.9 ng, per milliliter (S.D.) in February (n = 56) and 42.1 +/- 13.9 ng.per milliliter in August (n = 61). There was no significant racial difference in serum 25-OHD in February or August. No seasonal difference in calcium was noted but magnesium concentrations were lower in August. No correlation existed between serum 25-OHD and serum calcium or magnesium, parity, time from last pregnancy, maternal age, or social class. Concentrations of 25-OHD showed weak correlations with vitamin D intake (r = 0.32) and duration of gestation (r = 0.26) in the winter only. These data suggest that, regardless of race, ultraviolet exposure is the major determinant of maternal serum 25-OHD concentration in St. Louis. Dietary intake and and other factors may be important during periods of decreased ultraviolet exposure.", "contents": "Perinatal vitamin D metabolism. III. Factors influencing late gestational human serum 25-hydroxyvitamin D. Sera were obtained during the last trimester from both black and white women receiving prenatal care for determinations of calcium, magnesium, and 25-hydroxyvitamin D (25-OHD). The mean serum 25-OHD concentrations were 15.4 +/- 5.9 ng, per milliliter (S.D.) in February (n = 56) and 42.1 +/- 13.9 ng.per milliliter in August (n = 61). There was no significant racial difference in serum 25-OHD in February or August. No seasonal difference in calcium was noted but magnesium concentrations were lower in August. No correlation existed between serum 25-OHD and serum calcium or magnesium, parity, time from last pregnancy, maternal age, or social class. Concentrations of 25-OHD showed weak correlations with vitamin D intake (r = 0.32) and duration of gestation (r = 0.26) in the winter only. These data suggest that, regardless of race, ultraviolet exposure is the major determinant of maternal serum 25-OHD concentration in St. Louis. Dietary intake and and other factors may be important during periods of decreased ultraviolet exposure."} {"id": "PMID:1266892", "title": "Pycnodysostosis: some aspects concerning kinetics of calcium metabolism and bone pathology.", "content": "A 23-year-old white woman suffering pycnodysostosis whose parents and five siblings were unaffected was investigated. Chromosomal morphology was normal. Histologic examination of a biopsy specimen obtained from the distal phalanx of the left thumb, corresponding to an area on an x-ray film of osteolysis, showed a fibrous dysplasia-like picture. Kinetic studies of calcium metabolism revealed that exchangeable pool size, turnover, and bone accretion rate were all decreased. Intestinal calcium absorption was investigated simultaneously by a double isotope technique and by deconvolution of the plasmatic specific activity curve of 47Ca given per os. Results obtained by both methods coincided in that values were found to be similarly increased. Endogenous fecal calcium was also determined and revealed a similar increase. Some physiopathological implications of these findings are discussed.", "contents": "Pycnodysostosis: some aspects concerning kinetics of calcium metabolism and bone pathology. A 23-year-old white woman suffering pycnodysostosis whose parents and five siblings were unaffected was investigated. Chromosomal morphology was normal. Histologic examination of a biopsy specimen obtained from the distal phalanx of the left thumb, corresponding to an area on an x-ray film of osteolysis, showed a fibrous dysplasia-like picture. Kinetic studies of calcium metabolism revealed that exchangeable pool size, turnover, and bone accretion rate were all decreased. Intestinal calcium absorption was investigated simultaneously by a double isotope technique and by deconvolution of the plasmatic specific activity curve of 47Ca given per os. Results obtained by both methods coincided in that values were found to be similarly increased. Endogenous fecal calcium was also determined and revealed a similar increase. Some physiopathological implications of these findings are discussed."} {"id": "PMID:1266900", "title": "The effect of various vasoactive compounds upon the uterine vascular bed.", "content": "The effects of various vasodilators on the uterine vascular bed were investigated in nonpregnant, oophorectomized sheep with chronically implanted flow probes and catheters inserted into branches of the uterine arteries. A 1 mug dose of estradiol-17beta (0.224 muM) produces a maximum uterine blood flow response after intra-arterial injection. Adenosine (24 muM) and bradykinin (0.02 muM) were observed to increase blood flow to levels achieved by 1 mug of estradiol-17beta. Acetylcholine, isoproterenol, and histamine were less potent in their vasodilator activity. Atropine, propanolol, and diphenhydramine did not inhibit the increase of uterine blood flow induced by estrogens.", "contents": "The effect of various vasoactive compounds upon the uterine vascular bed. The effects of various vasodilators on the uterine vascular bed were investigated in nonpregnant, oophorectomized sheep with chronically implanted flow probes and catheters inserted into branches of the uterine arteries. A 1 mug dose of estradiol-17beta (0.224 muM) produces a maximum uterine blood flow response after intra-arterial injection. Adenosine (24 muM) and bradykinin (0.02 muM) were observed to increase blood flow to levels achieved by 1 mug of estradiol-17beta. Acetylcholine, isoproterenol, and histamine were less potent in their vasodilator activity. Atropine, propanolol, and diphenhydramine did not inhibit the increase of uterine blood flow induced by estrogens."} {"id": "PMID:1266901", "title": "Aspects of the normal psychology of pregnancy: the midtrimester.", "content": "In this study of nonpregnant women were compared with pregnant women. A set of feelings and attitudes along with questions relevant to the anatomy and physiology of parturition were the measures of comparison. The pregnant women and the nonpregnant women had almost identical feelings and attitudes. There were, however, three exceptions to this general condordance. They were: (1) the nonpregnant women's regard of pregnancy as a depressive and withdrawing experience, (2) a greater fear for the fetus among the nonpregnant women, and (3) higher scores on a pregnancy information inventory among the pregnant women.", "contents": "Aspects of the normal psychology of pregnancy: the midtrimester. In this study of nonpregnant women were compared with pregnant women. A set of feelings and attitudes along with questions relevant to the anatomy and physiology of parturition were the measures of comparison. The pregnant women and the nonpregnant women had almost identical feelings and attitudes. There were, however, three exceptions to this general condordance. They were: (1) the nonpregnant women's regard of pregnancy as a depressive and withdrawing experience, (2) a greater fear for the fetus among the nonpregnant women, and (3) higher scores on a pregnancy information inventory among the pregnant women."} {"id": "PMID:1266902", "title": "A high-risk pregnancy management protocol.", "content": "A simple hihg-risk pregnancy management protocol is presented. Three basic quantitative tests of fetal-placental function are utilized. The advantages and proper application and interpretation of these laboratory tools are discussed. Perinatal outcome is analyzed in the initial 225 high-risk pregnancies managed according to the protocol. Over 94% of the infants achieved 5 minute Apgar scores of 8 or above. The corrected perinatal mortality rate was only 8.8 per 1,000 live births.", "contents": "A high-risk pregnancy management protocol. A simple hihg-risk pregnancy management protocol is presented. Three basic quantitative tests of fetal-placental function are utilized. The advantages and proper application and interpretation of these laboratory tools are discussed. Perinatal outcome is analyzed in the initial 225 high-risk pregnancies managed according to the protocol. Over 94% of the infants achieved 5 minute Apgar scores of 8 or above. The corrected perinatal mortality rate was only 8.8 per 1,000 live births."} {"id": "PMID:1266903", "title": "Cortisol levels in umbilical cord plasma in relation to labor and delivery.", "content": "Cortisol was determined by a competitive protein-binding method in umbilical cord plasma from pregnancies of 37 or more weeks' gestation. In 162 cases of vaginal delivery following spontaneous labor the mean +/- S.E. of cortisol values was 7.43 +/- 0.29 mug per 100 ml. of plasma. This cortisol level was not significantly different from that observed in 51 cases of vaginal delivery after oxytocin-induced labor (6.53 +/- 0.49 mug per 100 ml.) or in 47 cases of delivery by emergency cesarean section following labor (6.21 +/- 0.66 mug per 100 ml.). The mean cortisol level in cases of elective cesarean section with no prior labor (4.67 +/- 0.60 mug per 100 ml.) was significantly less than the value for vaginal delivery after spontaneous or induced labor. The cord plasma and amniotic fluid concentrations of cortisol in a pregnancy complicated by fetal anencephaly and terminated at 44 weeks by induction were normal. It is concluded that labor and vaginal delivery resulted in a significant increase in cord plasma cortisol levels but there was no significant difference between spontaneous and induced labors. These findings do not support the hypothesis that a surge in fetal cortisol production immediately precedes and initiates spontaneous labor in human pregnancy.", "contents": "Cortisol levels in umbilical cord plasma in relation to labor and delivery. Cortisol was determined by a competitive protein-binding method in umbilical cord plasma from pregnancies of 37 or more weeks' gestation. In 162 cases of vaginal delivery following spontaneous labor the mean +/- S.E. of cortisol values was 7.43 +/- 0.29 mug per 100 ml. of plasma. This cortisol level was not significantly different from that observed in 51 cases of vaginal delivery after oxytocin-induced labor (6.53 +/- 0.49 mug per 100 ml.) or in 47 cases of delivery by emergency cesarean section following labor (6.21 +/- 0.66 mug per 100 ml.). The mean cortisol level in cases of elective cesarean section with no prior labor (4.67 +/- 0.60 mug per 100 ml.) was significantly less than the value for vaginal delivery after spontaneous or induced labor. The cord plasma and amniotic fluid concentrations of cortisol in a pregnancy complicated by fetal anencephaly and terminated at 44 weeks by induction were normal. It is concluded that labor and vaginal delivery resulted in a significant increase in cord plasma cortisol levels but there was no significant difference between spontaneous and induced labors. These findings do not support the hypothesis that a surge in fetal cortisol production immediately precedes and initiates spontaneous labor in human pregnancy."} {"id": "PMID:1266904", "title": "Relationship between cortisol levels in umbilical cord plasma and development of the respiratory distress syndrome in premature newborn infants.", "content": "The aim of this study was to determine whether there is a decrease in fetal cortisol levels associated with the respiratory distress syndrome (RDS). Eighteen newborn infants of less than 37 weeks' gestation who developed moderate to severe forms of RDS did have a significantly lower (P less than 0.02) mean cord plasma cortisol concentration at birth than that observed in 67 unaffected infants of similar gestational age; mean values +/- standard errors were 3.36 +/- 0.42 and 5.58 +/- 0.43 mug per 100 ml, respectively. However, whether or not RDS developed in neonates appeared to depend more upon the degree of prematurity (with a 71.5% incidence in gestations of less than 32 weeks compared to 17.1% in those of 32 to less than 37 weeks) than upon cortisol levels at delivery. Bood cortisol levels in the first days of life of four infants with RDS were considerably increased in comparison to those at birth. Mean cord plasma cortisol concentrations increased with duration of pregnancy, with the previously observed value for term infants (of 37 or more weeks) being approximately twice that for infants of less than 32 weeks' gestation. These findings appear to justify carefully controlled studied with antepartum glucocorticoid administration with the aim of reducing the incidence of RDS in premature newborn infants.", "contents": "Relationship between cortisol levels in umbilical cord plasma and development of the respiratory distress syndrome in premature newborn infants. The aim of this study was to determine whether there is a decrease in fetal cortisol levels associated with the respiratory distress syndrome (RDS). Eighteen newborn infants of less than 37 weeks' gestation who developed moderate to severe forms of RDS did have a significantly lower (P less than 0.02) mean cord plasma cortisol concentration at birth than that observed in 67 unaffected infants of similar gestational age; mean values +/- standard errors were 3.36 +/- 0.42 and 5.58 +/- 0.43 mug per 100 ml, respectively. However, whether or not RDS developed in neonates appeared to depend more upon the degree of prematurity (with a 71.5% incidence in gestations of less than 32 weeks compared to 17.1% in those of 32 to less than 37 weeks) than upon cortisol levels at delivery. Bood cortisol levels in the first days of life of four infants with RDS were considerably increased in comparison to those at birth. Mean cord plasma cortisol concentrations increased with duration of pregnancy, with the previously observed value for term infants (of 37 or more weeks) being approximately twice that for infants of less than 32 weeks' gestation. These findings appear to justify carefully controlled studied with antepartum glucocorticoid administration with the aim of reducing the incidence of RDS in premature newborn infants."} {"id": "PMID:1266918", "title": "Acute posterior multifocal placoid pigment epitheliopathy.", "content": "Thirteen cases of acute posterior multifocal placoid pigment epitheliopathy occurred in young adults or older children. In ten there was a characteristic, possibly infectious syndrome that preceded the onset of ocular manifestations by a few weeks. One patient developed cerebrospinal fluid lymphocytosis and a cerebral vasculitis coincident with the ocular changes. Extensive evaluations for viral and other infectious etiologies in this and other cases were unrevealing. An inflammatory reaction was observed in the anterior chambers of most patients, and cells were noted in the anterior vitreous bodies of a few patients. In one instance a serous detachment of the retina occurred adjacent to the optic disk. Our findings and others support the conclusion that the fundus lesions resulted from a multifocal choroiditis primarily involving the choriocapillaris and affecting the pigment epithelium and retina secondarily. The data also suggested that the choroiditis may be associated with a more widespread vasculitis occurring as an immune reaction to an earlier systemic infection.", "contents": "Acute posterior multifocal placoid pigment epitheliopathy. Thirteen cases of acute posterior multifocal placoid pigment epitheliopathy occurred in young adults or older children. In ten there was a characteristic, possibly infectious syndrome that preceded the onset of ocular manifestations by a few weeks. One patient developed cerebrospinal fluid lymphocytosis and a cerebral vasculitis coincident with the ocular changes. Extensive evaluations for viral and other infectious etiologies in this and other cases were unrevealing. An inflammatory reaction was observed in the anterior chambers of most patients, and cells were noted in the anterior vitreous bodies of a few patients. In one instance a serous detachment of the retina occurred adjacent to the optic disk. Our findings and others support the conclusion that the fundus lesions resulted from a multifocal choroiditis primarily involving the choriocapillaris and affecting the pigment epithelium and retina secondarily. The data also suggested that the choroiditis may be associated with a more widespread vasculitis occurring as an immune reaction to an earlier systemic infection."} {"id": "PMID:1266919", "title": "Severe solar maculopathy associated with the use of lysergic acid diethylamide (LSD).", "content": "A 23-year-old man sustained severe macular damage by sun gazing during a hallucinogenic drug-induced state. Sequential fundus photography and fluorescein angiography documented prominent focal injury to the retinal pigment epithelium.", "contents": "Severe solar maculopathy associated with the use of lysergic acid diethylamide (LSD). A 23-year-old man sustained severe macular damage by sun gazing during a hallucinogenic drug-induced state. Sequential fundus photography and fluorescein angiography documented prominent focal injury to the retinal pigment epithelium."} {"id": "PMID:1266920", "title": "Primary retinal detachments without apparent breaks.", "content": "In a prospective study of 415 consecutive eyes operated on for retinal detachment, there were no apparent retinal breaks in 41 eyes. Examination of the most likely site for breaks during, or shortly after, cryotherapy was helpful in detecting tiny breaks in several cases. All detachments without apparent breaks were operated on with a three-step operation: we applied two rows of confluent cryotherapy to all retinal breaks, drained subretinal fluid, and used buckles just anterior to the equator. Surgical cure, defined as reattachment for at least six months, was achieved in 93% of eyes with apparent breaks, and in 85% of eyes without apparent breaks. The latter figure increased to 91% when the seven patients with preoperative massive preretinal retraction were excluded.", "contents": "Primary retinal detachments without apparent breaks. In a prospective study of 415 consecutive eyes operated on for retinal detachment, there were no apparent retinal breaks in 41 eyes. Examination of the most likely site for breaks during, or shortly after, cryotherapy was helpful in detecting tiny breaks in several cases. All detachments without apparent breaks were operated on with a three-step operation: we applied two rows of confluent cryotherapy to all retinal breaks, drained subretinal fluid, and used buckles just anterior to the equator. Surgical cure, defined as reattachment for at least six months, was achieved in 93% of eyes with apparent breaks, and in 85% of eyes without apparent breaks. The latter figure increased to 91% when the seven patients with preoperative massive preretinal retraction were excluded."} {"id": "PMID:1266921", "title": "The architecture of the choriocapillaris at the posterior pole.", "content": "The afferent and efferent vessels as well as the choriocapillaris in the human posterior pole, studied in flat preparations, paraffin sections, and Epon sections, formed relatively discrete units of organization which we called lobules. A lobule is a segment of the choriocapillaris supplied centrally by a precapillary arteriole and demarcated peripherally by a ring of postcapillary venules. Observations on the choroidal phase of fundus fluorescein angiography indicated that blood entering a lobule did not intermingle with blood from adjoining lobules. The choriocapillaris in the posterior pole of the human eye, with its supplying and draining vessels, appeared as a mosaic of adjoining lobules that function independently.", "contents": "The architecture of the choriocapillaris at the posterior pole. The afferent and efferent vessels as well as the choriocapillaris in the human posterior pole, studied in flat preparations, paraffin sections, and Epon sections, formed relatively discrete units of organization which we called lobules. A lobule is a segment of the choriocapillaris supplied centrally by a precapillary arteriole and demarcated peripherally by a ring of postcapillary venules. Observations on the choroidal phase of fundus fluorescein angiography indicated that blood entering a lobule did not intermingle with blood from adjoining lobules. The choriocapillaris in the posterior pole of the human eye, with its supplying and draining vessels, appeared as a mosaic of adjoining lobules that function independently."} {"id": "PMID:1266922", "title": "Ghost cells as a cause of glaucoma.", "content": "Clinical and investigative evidence indicated a glaucoma caused mainly by degenerated red blood cells, or ghost cells. These ghost cells, with altered shape, color, and pliability, accumulated in the vitreous cavity after hemorrhage. Following disruption of the anterior hyaloid face, they passed into the anterior chamber and caused severe glaucoma. In the anterior chamber, the tiny, khakicolored cells, circulating slowly, were frequently mistaken for white blood cells. They covered the trabecular meshwork or filled the inferior angle with a pathognomonic khaki-colored layer. They were identified by phase-contrast microscopic examination of anterior chamber aspirates. The decreased pliability of these degenerated cells seemed to account for their inability to pass easily through the human trabecular meshwork and, therefore, to cause severe glaucoma.", "contents": "Ghost cells as a cause of glaucoma. Clinical and investigative evidence indicated a glaucoma caused mainly by degenerated red blood cells, or ghost cells. These ghost cells, with altered shape, color, and pliability, accumulated in the vitreous cavity after hemorrhage. Following disruption of the anterior hyaloid face, they passed into the anterior chamber and caused severe glaucoma. In the anterior chamber, the tiny, khakicolored cells, circulating slowly, were frequently mistaken for white blood cells. They covered the trabecular meshwork or filled the inferior angle with a pathognomonic khaki-colored layer. They were identified by phase-contrast microscopic examination of anterior chamber aspirates. The decreased pliability of these degenerated cells seemed to account for their inability to pass easily through the human trabecular meshwork and, therefore, to cause severe glaucoma."} {"id": "PMID:1266923", "title": "Experimental iridectomy with bipolar microcautery.", "content": "Peripheral iridectomy was performed in pigmented rabbits after the application of bipolar microcautery to the iris surface. At low doses of cautery, no increase in postoperative inflammation or complications was noted clinically or pathologically in control eyes. High doses of cautery resulted in an increased incidence of postoperative inflammation, corneal opacity, hyphema, iris prolapse, lens changes, and poor wound healing.", "contents": "Experimental iridectomy with bipolar microcautery. Peripheral iridectomy was performed in pigmented rabbits after the application of bipolar microcautery to the iris surface. At low doses of cautery, no increase in postoperative inflammation or complications was noted clinically or pathologically in control eyes. High doses of cautery resulted in an increased incidence of postoperative inflammation, corneal opacity, hyphema, iris prolapse, lens changes, and poor wound healing."} {"id": "PMID:1266924", "title": "Acute glaucoma in hemorrhagic fever with renal syndrome (nephropathia epidemica).", "content": "Bilateral eyelid edema, chemosis, conjunctival injection and hemorrhages, shallowing of the anterior chamber with transitory myopia, and acute glaucoma were observed in three patients with hemorrhagic fever with renal syndrome (nephropathia epidemica). One patient had anterior uveitis with posterior synechiae. Two patients had congestion of retinal venules and retinal edema, and one patient had small retinal hemorrhages. Fluorescein angiography revealed early leakage of the conjunctival capillaries and delayed filling of the lower retinal arterioles with retinal edema. The acute glaucoma subsided rapidly. The myopia disappeared slowly with a gradual deepening of the anterior chamber after onset of the diuretic phase of the illness. In nephropathia epidemica, the transitory shallowing of the anterior chamber, myopia, and acute glaucoma are due to lesions in the small blood vessels of the ciliary body, resulting in its swelling, with relaxation of the zonules and forward movement of the lens.", "contents": "Acute glaucoma in hemorrhagic fever with renal syndrome (nephropathia epidemica). Bilateral eyelid edema, chemosis, conjunctival injection and hemorrhages, shallowing of the anterior chamber with transitory myopia, and acute glaucoma were observed in three patients with hemorrhagic fever with renal syndrome (nephropathia epidemica). One patient had anterior uveitis with posterior synechiae. Two patients had congestion of retinal venules and retinal edema, and one patient had small retinal hemorrhages. Fluorescein angiography revealed early leakage of the conjunctival capillaries and delayed filling of the lower retinal arterioles with retinal edema. The acute glaucoma subsided rapidly. The myopia disappeared slowly with a gradual deepening of the anterior chamber after onset of the diuretic phase of the illness. In nephropathia epidemica, the transitory shallowing of the anterior chamber, myopia, and acute glaucoma are due to lesions in the small blood vessels of the ciliary body, resulting in its swelling, with relaxation of the zonules and forward movement of the lens."} {"id": "PMID:1266925", "title": "Relative afferent pupillary defect in glaucoma.", "content": "Seven patients with asymmetrical open-angle glaucoma had relative afferent pupillary defects. This defect may have occurred during any stage of glaucoma, but the presence of this sign may be indicative of the earliest onset of optic nerve damage in patients with ocular hypertension. Although the presence of an afferent pupillary defect should suggest the consideration of a neurologic lesion, glaucomatous damage may be the sole explanation for this phenomenon.", "contents": "Relative afferent pupillary defect in glaucoma. Seven patients with asymmetrical open-angle glaucoma had relative afferent pupillary defects. This defect may have occurred during any stage of glaucoma, but the presence of this sign may be indicative of the earliest onset of optic nerve damage in patients with ocular hypertension. Although the presence of an afferent pupillary defect should suggest the consideration of a neurologic lesion, glaucomatous damage may be the sole explanation for this phenomenon."} {"id": "PMID:1266926", "title": "Glycerol and hyperosmolar nonketotic coma.", "content": "Hyperosmolar nonketotic coma occurred in a 29-year-old diabetic man with chronic renal failure after the repeated use of oral glycerol for treatment of acute neovascular glaucoma. Treatment with intravenous hypotonic saline, albumin, and packed red blood cells together with insulin and bicarbonate was successful in overcoming the coma.", "contents": "Glycerol and hyperosmolar nonketotic coma. Hyperosmolar nonketotic coma occurred in a 29-year-old diabetic man with chronic renal failure after the repeated use of oral glycerol for treatment of acute neovascular glaucoma. Treatment with intravenous hypotonic saline, albumin, and packed red blood cells together with insulin and bicarbonate was successful in overcoming the coma."} {"id": "PMID:1266928", "title": "Endothelial damage associated with intraocular lenses.", "content": "We examined the corneal endothelium of five patients with the clinical specular microscope before and at intervals after combined cataract extraction and intraocular lens implantation. There was a severe loss of endothelial cells postoperatively in all five patients despite clear, thin corneas. We observed no significant endothelial regeneration (increased number of cells) or continued cell loss during 15 weeks of postoperative observation. The clinical specular microscope was useful in assessing the endothelial effects of ocular surgical procedures.", "contents": "Endothelial damage associated with intraocular lenses. We examined the corneal endothelium of five patients with the clinical specular microscope before and at intervals after combined cataract extraction and intraocular lens implantation. There was a severe loss of endothelial cells postoperatively in all five patients despite clear, thin corneas. We observed no significant endothelial regeneration (increased number of cells) or continued cell loss during 15 weeks of postoperative observation. The clinical specular microscope was useful in assessing the endothelial effects of ocular surgical procedures."} {"id": "PMID:1266927", "title": "Comparative toxicity of intraocular irrigating solutions on the corneal endothelium.", "content": "Isolated rabbit and human corneas were perfused in vitro with Plasma-lyte 148 solution and with a glutathione bicarbonate Ringer's solution. The corneal swelling rate and ultrastructure were compared to corneas perfused with three commonly used intraocular irrigating solutions. Corneas perfused with Plasma-lyte 148 swelled at a rate of 47 mu/gr and the endothelial cells separated from each other and showed extensive damage after three hours of perfusion. By comparison, corneas perfused with 0.9% NaCl increased in thickness by 98 mu/hr, lactated Ringer's by 39 mu/hr, balanced salt solution by 24 mu/hr, and glutathione bicarbonate Ringer's solution by 4 mu/hr. These results indicate that endothelial cell damage and increased corneal thickness observed during perfusion was related to the incomplete composition of 0.9% NaCl, Plasma-lyte 148, and lactated Ringer's and that endothelial cell damage can be prevented if the intraocular irrigating solution contains concentrations of inorganic and organic constituents that are similar to those in aqueous humor.", "contents": "Comparative toxicity of intraocular irrigating solutions on the corneal endothelium. Isolated rabbit and human corneas were perfused in vitro with Plasma-lyte 148 solution and with a glutathione bicarbonate Ringer's solution. The corneal swelling rate and ultrastructure were compared to corneas perfused with three commonly used intraocular irrigating solutions. Corneas perfused with Plasma-lyte 148 swelled at a rate of 47 mu/gr and the endothelial cells separated from each other and showed extensive damage after three hours of perfusion. By comparison, corneas perfused with 0.9% NaCl increased in thickness by 98 mu/hr, lactated Ringer's by 39 mu/hr, balanced salt solution by 24 mu/hr, and glutathione bicarbonate Ringer's solution by 4 mu/hr. These results indicate that endothelial cell damage and increased corneal thickness observed during perfusion was related to the incomplete composition of 0.9% NaCl, Plasma-lyte 148, and lactated Ringer's and that endothelial cell damage can be prevented if the intraocular irrigating solution contains concentrations of inorganic and organic constituents that are similar to those in aqueous humor."} {"id": "PMID:1266929", "title": "Corneal endothelial degeneration and fibrous proliferation after plana vitrectomy.", "content": "A 45-year-old woman with juvenile-onset diabetes had persistent corneal edema after a pars plana vitrectomy and lensectomy procedure. Phase contrast and electron microscopic observation of the patient's cornea revealed extreme attenuation of the endothelial cell layer and abnormal collagenous and basement membrane material interposed between Descemet's membrane and the endothelium. Endothelial fibrous proliferations in this case were consistent with the development of ultrastructurally identical fibrous proliferations in many other situations involving dysfunction of the corneal endothelium.", "contents": "Corneal endothelial degeneration and fibrous proliferation after plana vitrectomy. A 45-year-old woman with juvenile-onset diabetes had persistent corneal edema after a pars plana vitrectomy and lensectomy procedure. Phase contrast and electron microscopic observation of the patient's cornea revealed extreme attenuation of the endothelial cell layer and abnormal collagenous and basement membrane material interposed between Descemet's membrane and the endothelium. Endothelial fibrous proliferations in this case were consistent with the development of ultrastructurally identical fibrous proliferations in many other situations involving dysfunction of the corneal endothelium."} {"id": "PMID:1266930", "title": "Autofluorescence of the human diabetic lens in vivo.", "content": "We studied the in vivo measurements of the autofluorescence of the clear lens in 80 juvenile diabetics and 25 young healthy subjects. When the diabetes was of seven years' duration or more, no overlap with the control subjects was found. The pathologic autofluorescence of the diabetic lens showed a positive correlation with age and the duration of diabetes.", "contents": "Autofluorescence of the human diabetic lens in vivo. We studied the in vivo measurements of the autofluorescence of the clear lens in 80 juvenile diabetics and 25 young healthy subjects. When the diabetes was of seven years' duration or more, no overlap with the control subjects was found. The pathologic autofluorescence of the diabetic lens showed a positive correlation with age and the duration of diabetes."} {"id": "PMID:1266931", "title": "Tissue, tear, and serum IgE concentrations in vernal conjunctivitis.", "content": "Abnormal upper tarsal tissue from four patients with vernal conjunctivitis stained immunofluorescently contained abundant IgA-, IgD-, and IgE-forming plasma cells in two of four patients. These were absent in normal upper tarsal conjunctiva. The IgE levels of paired tear-serum samples of 11 patients with vernal conjunctivitis and ten control subjects were 130 ng/ml in patients that did nor differ significantly from the normal tear IgE value of 61 ng/ml. The serum IgE means of 1,031 ng/ml for patients and 201 ng/ml for normal subjects differed significantly (P less than .05). Tear and serum IgE values correlated significantly for both groups (P less than .01 for patients, P less than .05 for normal subjects). These findings are consistent with a hyperplasia of IgA, IgD, and IgE antibody-forming cells in tarsal conjunctiva of some patients with vernal conjunctivitis, and tear IgE levels being a function of serum IgE levels.", "contents": "Tissue, tear, and serum IgE concentrations in vernal conjunctivitis. Abnormal upper tarsal tissue from four patients with vernal conjunctivitis stained immunofluorescently contained abundant IgA-, IgD-, and IgE-forming plasma cells in two of four patients. These were absent in normal upper tarsal conjunctiva. The IgE levels of paired tear-serum samples of 11 patients with vernal conjunctivitis and ten control subjects were 130 ng/ml in patients that did nor differ significantly from the normal tear IgE value of 61 ng/ml. The serum IgE means of 1,031 ng/ml for patients and 201 ng/ml for normal subjects differed significantly (P less than .05). Tear and serum IgE values correlated significantly for both groups (P less than .01 for patients, P less than .05 for normal subjects). These findings are consistent with a hyperplasia of IgA, IgD, and IgE antibody-forming cells in tarsal conjunctiva of some patients with vernal conjunctivitis, and tear IgE levels being a function of serum IgE levels."} {"id": "PMID:1266932", "title": "Lower eyelid reconstruction by tarsal transposition.", "content": "We reconstructed the lower eyelids of 13 patients using a tarsoconjunctival flap from the upper eyelid. The laterally based pedicle flap permitted a one-stage repair without prolonged occlusion of the eye. The technique was best suited to lesions involving the lateral aspect of the lower eyelid, but can be applied to lesions of the central and medial eyelid. The functional and cosmetic results were equal or superior to tarsoconjunctival advancement flaps.", "contents": "Lower eyelid reconstruction by tarsal transposition. We reconstructed the lower eyelids of 13 patients using a tarsoconjunctival flap from the upper eyelid. The laterally based pedicle flap permitted a one-stage repair without prolonged occlusion of the eye. The technique was best suited to lesions involving the lateral aspect of the lower eyelid, but can be applied to lesions of the central and medial eyelid. The functional and cosmetic results were equal or superior to tarsoconjunctival advancement flaps."} {"id": "PMID:1266933", "title": "Anaerobic streptococcal corneal ulcer.", "content": "An anaerobic streptococcus caused a central corneal ulcer in a 10-year-old girl. There were no identifying clinical findings. The lesion healed promptly and satisfactorily with antibiotic therapy.", "contents": "Anaerobic streptococcal corneal ulcer. An anaerobic streptococcus caused a central corneal ulcer in a 10-year-old girl. There were no identifying clinical findings. The lesion healed promptly and satisfactorily with antibiotic therapy."} {"id": "PMID:1266938", "title": "Field work experience ratings and certification examination scores as predictors of job performance and satisfaction in occupational therapy.", "content": "The American Occupational Therapy Association's certification instruments, the Certification Examination for Occupational Therapists Registered and the Field Work Performance Report, were examined in terms of their ability to predict future job performance and satisfaction of occupational therapists. A job satisfaction questionnaire was administered to 208 occupational therapists, and their supervisors rated them on a job performance instrument. The resulting correlations between these work adjustment variables and the previously administered certification instruments failed to reveal any predictive ability. Some plausible reasons for these negative results and possible directions for further research into this professional screening process were explored.", "contents": "Field work experience ratings and certification examination scores as predictors of job performance and satisfaction in occupational therapy. The American Occupational Therapy Association's certification instruments, the Certification Examination for Occupational Therapists Registered and the Field Work Performance Report, were examined in terms of their ability to predict future job performance and satisfaction of occupational therapists. A job satisfaction questionnaire was administered to 208 occupational therapists, and their supervisors rated them on a job performance instrument. The resulting correlations between these work adjustment variables and the previously administered certification instruments failed to reveal any predictive ability. Some plausible reasons for these negative results and possible directions for further research into this professional screening process were explored."} {"id": "PMID:1266939", "title": "Community-based learning in occupational therapy.", "content": "A community-based field work experience for senior occupational therapy students is described. The program was designed to meet five objectives: to provide students with an effective integration of theory and practice; to allow an application of theoretical concepts to early intervention and prevention programs; to enable students to confront complexities of community service delivery; to allow students to learn new roles in community programs; and to demonstrate the role of occupational therapy within a public health model of service delivery. In addition to these project objectives, placement sites, student roles, and organization of supervision are discussed. Examples are given to illustrate the diversity of student experience. Student and consumer feedback indicated that positive gains had been made toward fulfillment of the project objectives.", "contents": "Community-based learning in occupational therapy. A community-based field work experience for senior occupational therapy students is described. The program was designed to meet five objectives: to provide students with an effective integration of theory and practice; to allow an application of theoretical concepts to early intervention and prevention programs; to enable students to confront complexities of community service delivery; to allow students to learn new roles in community programs; and to demonstrate the role of occupational therapy within a public health model of service delivery. In addition to these project objectives, placement sites, student roles, and organization of supervision are discussed. Examples are given to illustrate the diversity of student experience. Student and consumer feedback indicated that positive gains had been made toward fulfillment of the project objectives."} {"id": "PMID:1266940", "title": "The relationship between occupational therapy and physical therapy test scores in children with learning disabilities.", "content": "Twenty-seven children with learning disabilities associated with perceptual deficits were studied in order to determine what relationship might exist between occupational therapy and physical therapy test scores. Intercorrelations were computed and multivariate models were developed for the occupational therapy test items. Numerous positive relationships were demonstrated between the two groups of test items, consistent with previous clinical and experimental data. One test, however, did not duplicate the other, and both are essential in the evaluation of the learning-disabled child with perceptual deficits. Negative correlations also emerged, which might have been caused by compensation for deficits.", "contents": "The relationship between occupational therapy and physical therapy test scores in children with learning disabilities. Twenty-seven children with learning disabilities associated with perceptual deficits were studied in order to determine what relationship might exist between occupational therapy and physical therapy test scores. Intercorrelations were computed and multivariate models were developed for the occupational therapy test items. Numerous positive relationships were demonstrated between the two groups of test items, consistent with previous clinical and experimental data. One test, however, did not duplicate the other, and both are essential in the evaluation of the learning-disabled child with perceptual deficits. Negative correlations also emerged, which might have been caused by compensation for deficits."} {"id": "PMID:1266942", "title": "Unusual intranuclear filaments in the circulating lymphocytes of patients with multiple sclerosis and optic neuritis.", "content": "Mononuclear cells obtained from the peripheral blood of patients with multiple sclerosis (MS) and optic neuritis (ON) were examined by electron microscopy. Unusual intranuclear filaments identical with the so-called paramyxovirus-like filaments were found in circulating lymphocytes from 5 patients with MS and 3 with ON. They were observed in 0.1 to 0.5% of the mononuclear cells. Electron microscopy of the blood cells from 5 other patients with ON, 3 patients with neurologic diseases other than MS, and 4 normal subjects failed to reveal similar structures. The filaments were also absent from blood cells from blood cells from normal subjects during the process of autolysis.", "contents": "Unusual intranuclear filaments in the circulating lymphocytes of patients with multiple sclerosis and optic neuritis. Mononuclear cells obtained from the peripheral blood of patients with multiple sclerosis (MS) and optic neuritis (ON) were examined by electron microscopy. Unusual intranuclear filaments identical with the so-called paramyxovirus-like filaments were found in circulating lymphocytes from 5 patients with MS and 3 with ON. They were observed in 0.1 to 0.5% of the mononuclear cells. Electron microscopy of the blood cells from 5 other patients with ON, 3 patients with neurologic diseases other than MS, and 4 normal subjects failed to reveal similar structures. The filaments were also absent from blood cells from blood cells from normal subjects during the process of autolysis."} {"id": "PMID:1266943", "title": "Nonpathogenicity of antiintestinal antibody in the rabbit.", "content": "Rabbits were immunized with intestinal extract prepared from rabbits, guinea pigs, and germ-free rats. The resultant serum antibody response to intestinal antigen was determined by gel precipitation and direct tissue immunofluorescence. Forty-eight hours prior to sacrifice of each immunized animal, a portion of the duodenum, ileum, and colon were traumatized to bring circulating antibody into contact with the tissue. Sections for histology and direct immunofluorescence were taken from the area of trauma, just adjacent to the area, and 10 cm from it. The humoral immune response, the presence of tissue bound immunoglobulin, and tissue histology were compared. The area of trauma in normal and immunized animals showed the same histologic changes. In each animal, tissue just adjacent to the area of trauma and 10 cm from it were histologically identical. The pathologic alterations in the immunized animals were similar to those associated with malabsorption in man. Direct immunofluorescence of the intestinal tissue revealed bound immunoglobulin in histologically normal and abnormal tissue. Precipitating antibody to intestine was present in the serum of rabbits with normal and abnormal histology. Thus, antiintestinal antibody as dected by precipitation in gel and direct tissue immunofluorescence does not appear to be a factor in the pathogenesis of this model of immunologically induced histologic changes in the intestine.", "contents": "Nonpathogenicity of antiintestinal antibody in the rabbit. Rabbits were immunized with intestinal extract prepared from rabbits, guinea pigs, and germ-free rats. The resultant serum antibody response to intestinal antigen was determined by gel precipitation and direct tissue immunofluorescence. Forty-eight hours prior to sacrifice of each immunized animal, a portion of the duodenum, ileum, and colon were traumatized to bring circulating antibody into contact with the tissue. Sections for histology and direct immunofluorescence were taken from the area of trauma, just adjacent to the area, and 10 cm from it. The humoral immune response, the presence of tissue bound immunoglobulin, and tissue histology were compared. The area of trauma in normal and immunized animals showed the same histologic changes. In each animal, tissue just adjacent to the area of trauma and 10 cm from it were histologically identical. The pathologic alterations in the immunized animals were similar to those associated with malabsorption in man. Direct immunofluorescence of the intestinal tissue revealed bound immunoglobulin in histologically normal and abnormal tissue. Precipitating antibody to intestine was present in the serum of rabbits with normal and abnormal histology. Thus, antiintestinal antibody as dected by precipitation in gel and direct tissue immunofluorescence does not appear to be a factor in the pathogenesis of this model of immunologically induced histologic changes in the intestine."} {"id": "PMID:1266944", "title": "Localization of platelet prostaglandin production in the platelet dense tubular system.", "content": "Platelet production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5,10-heptadecadienoic acid (PHD), two metabolites of the prostaglandin cyclic endoperoxides PGG2 and PGH2, was found in this investigation to occur primarily in a platelet microsomal fraction consisting almost exclusively of membranes. To further localize the membrane site of platelet prostaglandin biosynthesis, the present study has used a cytochemical technique employing 3,3'-diaminobenzidine as an oxidizable substrate. The reaction product was found to localize in the platelet dense tubular system. Formation of the reaction product was inhibited by aminotriazole. In similar concentrations, aminotriazole inhibited collagen and arachidonic acid aggregation, the second wave of ADP and epinephrine aggregation, but failed to inhibit aggregation by PGG2 and A23187. A study of the mechanism of action of aminotriazole revealed inhibition of formation of HHT and PHD. The results localize platelet prostaglandin biosynthesis to the membranes of the dense tubular system.", "contents": "Localization of platelet prostaglandin production in the platelet dense tubular system. Platelet production of 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9, 12L-dihydroxy-5,10-heptadecadienoic acid (PHD), two metabolites of the prostaglandin cyclic endoperoxides PGG2 and PGH2, was found in this investigation to occur primarily in a platelet microsomal fraction consisting almost exclusively of membranes. To further localize the membrane site of platelet prostaglandin biosynthesis, the present study has used a cytochemical technique employing 3,3'-diaminobenzidine as an oxidizable substrate. The reaction product was found to localize in the platelet dense tubular system. Formation of the reaction product was inhibited by aminotriazole. In similar concentrations, aminotriazole inhibited collagen and arachidonic acid aggregation, the second wave of ADP and epinephrine aggregation, but failed to inhibit aggregation by PGG2 and A23187. A study of the mechanism of action of aminotriazole revealed inhibition of formation of HHT and PHD. The results localize platelet prostaglandin biosynthesis to the membranes of the dense tubular system."} {"id": "PMID:1266945", "title": "Kinetics of epidermal production during epidermal regeneration following abrasion in mice.", "content": "A technique is presented which allows us to measure total increases in epidermal wet weight on the back of a mouse during epidermal regeneration, thus for the first time permitting us to determine the kinetics of increase of epidermal mass during epidermal regeneration. Within 2 days after removal of the epidermis by abrasion with an emery wheel, in mice in the resting phase of the hair growth cycle, the epidermis begins to be regenerated from the cells of the underlying resting hair follicles. By Day 3 epidermal wet weight is 70% of normal. By Day 4 it is 1.97 times normal and reaches its peak of 3.8 times normal by 5 days. Associated with this increase in epidermal wet weight is a two times increase in the number of epidermal cells per millimeter of interfollicular epidermis. However, the change in the number of cells is not uniform for all types of epidermal cells. Suprabasal cells increase 4.6 times by 7 days, whereas the basal cells actually decrease to 60% of normal levels. Colchicine mitotic count is increased almost 18-fold by Day 3 and remains above control levels for the rest of the experimental period. Many mitoses appear in the suprabasal layers.", "contents": "Kinetics of epidermal production during epidermal regeneration following abrasion in mice. A technique is presented which allows us to measure total increases in epidermal wet weight on the back of a mouse during epidermal regeneration, thus for the first time permitting us to determine the kinetics of increase of epidermal mass during epidermal regeneration. Within 2 days after removal of the epidermis by abrasion with an emery wheel, in mice in the resting phase of the hair growth cycle, the epidermis begins to be regenerated from the cells of the underlying resting hair follicles. By Day 3 epidermal wet weight is 70% of normal. By Day 4 it is 1.97 times normal and reaches its peak of 3.8 times normal by 5 days. Associated with this increase in epidermal wet weight is a two times increase in the number of epidermal cells per millimeter of interfollicular epidermis. However, the change in the number of cells is not uniform for all types of epidermal cells. Suprabasal cells increase 4.6 times by 7 days, whereas the basal cells actually decrease to 60% of normal levels. Colchicine mitotic count is increased almost 18-fold by Day 3 and remains above control levels for the rest of the experimental period. Many mitoses appear in the suprabasal layers."} {"id": "PMID:1266946", "title": "Cyclodextrin nephrosis in the rat.", "content": "The renal toxicity of the Schardinger dextrins, alpha and beta-cyclodextrin, is manifested as a series of alterations in the vacuolar organelles of the proximal convoluted tubule. These changes begin as an increase of apical vacuoles and the appearance of giant lysosomes. The giant lysosomes characteristic of cyclodextrin nephrosis are notable because of the prominent acicular microcrystals embedded in the lysosomal matrix. Giant vacuoles devoid of acid phosphatase reaction product are found in advanced lesions. The vacuolar apparatus shows advanced changes prior to manifestation of lesions in mitochondria and other organelles. These observations indicate a role of the vacuologenic apparatus in the nephrotic process. Intracellular concentration of toxin via the lysosomal pathway represents a perversion of the physiologic function of the proximal tubule which ultimately leads to cell death.", "contents": "Cyclodextrin nephrosis in the rat. The renal toxicity of the Schardinger dextrins, alpha and beta-cyclodextrin, is manifested as a series of alterations in the vacuolar organelles of the proximal convoluted tubule. These changes begin as an increase of apical vacuoles and the appearance of giant lysosomes. The giant lysosomes characteristic of cyclodextrin nephrosis are notable because of the prominent acicular microcrystals embedded in the lysosomal matrix. Giant vacuoles devoid of acid phosphatase reaction product are found in advanced lesions. The vacuolar apparatus shows advanced changes prior to manifestation of lesions in mitochondria and other organelles. These observations indicate a role of the vacuologenic apparatus in the nephrotic process. Intracellular concentration of toxin via the lysosomal pathway represents a perversion of the physiologic function of the proximal tubule which ultimately leads to cell death."} {"id": "PMID:1266947", "title": "Child advocacy: a perspective.", "content": "Child advocacy provides a vehicle for building checks into systems that fail children. This paper examines the assumptions underlying child advocacy efforts, the types of child advocacy programs that have developed in the past few years, and the types of strategies used by child advocates.", "contents": "Child advocacy: a perspective. Child advocacy provides a vehicle for building checks into systems that fail children. This paper examines the assumptions underlying child advocacy efforts, the types of child advocacy programs that have developed in the past few years, and the types of strategies used by child advocates."} {"id": "PMID:1266948", "title": "The impact of the child's deficiency on the father: a study of fathers of mentally retarded and of chronically ill children.", "content": "Psychological assessments of fathers of mentally retarded, of chronically ill, and of healthy children indicate that the first two groups undergo significant stress associated with their fathering a handicapped child. Some fathers of mentally retarded children appear subject to a pattern of neurotic-like constriction. Differences in the experiences of fathers and mothers of deficient children are discussed, and suggestions for treatment are offered.", "contents": "The impact of the child's deficiency on the father: a study of fathers of mentally retarded and of chronically ill children. Psychological assessments of fathers of mentally retarded, of chronically ill, and of healthy children indicate that the first two groups undergo significant stress associated with their fathering a handicapped child. Some fathers of mentally retarded children appear subject to a pattern of neurotic-like constriction. Differences in the experiences of fathers and mothers of deficient children are discussed, and suggestions for treatment are offered."} {"id": "PMID:1266949", "title": "The effects of parental divorce: experiences of the child in later latency.", "content": "This paper discusses the impact of divorce on 31 children in later latency, as observed shortly after the initial parental separation and one year later. The material is part of an on-going clinical study, begun in 1970, of 131 children and adolescents from 60 divorcing families in Northern California.", "contents": "The effects of parental divorce: experiences of the child in later latency. This paper discusses the impact of divorce on 31 children in later latency, as observed shortly after the initial parental separation and one year later. The material is part of an on-going clinical study, begun in 1970, of 131 children and adolescents from 60 divorcing families in Northern California."} {"id": "PMID:1266950", "title": "Relational and behavioral interventions with economically disadvantaged toddlers.", "content": "Matched groups of children, ages 12-24 months, referred for early social or verbal developmental lags or home-environment problems, participated either in a center-based \"relational\" or a home-based \"behavior modification\" intervention. Although both programs accelerated youngsters' intellectual development, there were few differences between groups on the criterion change measures.", "contents": "Relational and behavioral interventions with economically disadvantaged toddlers. Matched groups of children, ages 12-24 months, referred for early social or verbal developmental lags or home-environment problems, participated either in a center-based \"relational\" or a home-based \"behavior modification\" intervention. Although both programs accelerated youngsters' intellectual development, there were few differences between groups on the criterion change measures."} {"id": "PMID:1266951", "title": "Some aspects of adoption in selected samples of adult adoptees.", "content": "Various aspects of adoption--psychopathology, age at placement, agency versus independent placement, best age to tell child he is adopted, etc.--are studied in three groups of adoptees: biological parent schizophrenic or manic-depressive; adoptive parent schizoprenic or manic-depressive; biological parent with no psychiatric history. Findings raise questions about a number of common assumptions regarding adoptees.", "contents": "Some aspects of adoption in selected samples of adult adoptees. Various aspects of adoption--psychopathology, age at placement, agency versus independent placement, best age to tell child he is adopted, etc.--are studied in three groups of adoptees: biological parent schizophrenic or manic-depressive; adoptive parent schizoprenic or manic-depressive; biological parent with no psychiatric history. Findings raise questions about a number of common assumptions regarding adoptees."} {"id": "PMID:1266952", "title": "Relationships between symptomatology and SES-related factors in hyperkinetic/MBD boys.", "content": "Relationships among symptomatology, socioeconomic status, and parenting styles were examined for 113 hyperkinetic/minimal brain dysfunction boys from intact families. Primary symptoms (e.g. hyperactivity) did not vary as a function of SES, but SES-related differences emerged for secondary symptoms (e.g., aggressive behavior, self-esteem deficits) and for parenting variables. Parenting variables were found to be better predictors of secondary symptoms than was SES. Implications for further research are offered.", "contents": "Relationships between symptomatology and SES-related factors in hyperkinetic/MBD boys. Relationships among symptomatology, socioeconomic status, and parenting styles were examined for 113 hyperkinetic/minimal brain dysfunction boys from intact families. Primary symptoms (e.g. hyperactivity) did not vary as a function of SES, but SES-related differences emerged for secondary symptoms (e.g., aggressive behavior, self-esteem deficits) and for parenting variables. Parenting variables were found to be better predictors of secondary symptoms than was SES. Implications for further research are offered."} {"id": "PMID:1266953", "title": "Sequential withdrawal of stimulant drugs and use of behavior therapy with two hyperactive boys.", "content": "The separate and combined effects of stimulant drugs, placebos, and behavior therapy were investigated with two hyperactive boys. In each case, sequential replacement of drugs (Ritalin and Dexedrine) with placebos demonstrated placebo effects of the drugs; behavior therapy, alone and in combination with drugs, was effective in controlling hyperactive behaviors. Implications in regard to drugs as treatment of choice are discussed.", "contents": "Sequential withdrawal of stimulant drugs and use of behavior therapy with two hyperactive boys. The separate and combined effects of stimulant drugs, placebos, and behavior therapy were investigated with two hyperactive boys. In each case, sequential replacement of drugs (Ritalin and Dexedrine) with placebos demonstrated placebo effects of the drugs; behavior therapy, alone and in combination with drugs, was effective in controlling hyperactive behaviors. Implications in regard to drugs as treatment of choice are discussed."} {"id": "PMID:1266954", "title": "Current medical practice and hyperactive children.", "content": "An extensive questionnaire was completed by 48 physicians, detailing the medical and behavioral information they collect in forming a diagnosis of conditions that have hyperactive behavior as a symptom. Results indicate that diagnoses are made primarily on the basis of behavioral indicators, and indicators and information from the child's personal medical history, rather than from other data collected during the physical exam.", "contents": "Current medical practice and hyperactive children. An extensive questionnaire was completed by 48 physicians, detailing the medical and behavioral information they collect in forming a diagnosis of conditions that have hyperactive behavior as a symptom. Results indicate that diagnoses are made primarily on the basis of behavioral indicators, and indicators and information from the child's personal medical history, rather than from other data collected during the physical exam."} {"id": "PMID:1266955", "title": "System for averaging physiological data recorded on film or paper.", "content": "A simple electro-mechanical system has been constructed to convert photographically-recorded data into a form that can be readily handled by a small, special-purpose averaging computer. Manual tracing of a series of records results in the production of an immediate and highly reproducible average response. The method has proven to be particularly useful in the analysis of electromyograms obtained during various form of locomotion.", "contents": "System for averaging physiological data recorded on film or paper. A simple electro-mechanical system has been constructed to convert photographically-recorded data into a form that can be readily handled by a small, special-purpose averaging computer. Manual tracing of a series of records results in the production of an immediate and highly reproducible average response. The method has proven to be particularly useful in the analysis of electromyograms obtained during various form of locomotion."} {"id": "PMID:1266956", "title": "Microscopic features and transient contraction of palpable bands in canine muscle.", "content": "Ten pairs of biopsies were excised from gracilis and semitendinosus muscles of 4 mongrel dogs. These were compared with the histological findings reported in painful spots and muscle hardenings of human muscles. Test biopsies sampled a palpable band. Paired control biopsies sampled a portion of the same muscle where it showed no palpable hardening. Processed sections were randomized and read blind. Sections stained with aqueous toluidine blue showed no convincing metachromasia. Sections stained with trichrome showed no proliferation of endomysial connective tissue. Test sections stained with hematoxylin and eosin showed no proliferation of nuclei and no increase in the number of central nuclei in muscle fibers compared to control sections. No convincing histological difference was found. During surgery under Nembutal anesthesia, rubbing palpation of the exposed muscle elicited a transient contraction of a bundle of muscle fibers several milli-meters in diameter. This corresponded in time and position to the palpable band in the dog muscle. The band-like hardness palpated in these canine muscles appears to be caused by a circumscribed transient muscular contraction rather than histologically demonstrable structural changes.", "contents": "Microscopic features and transient contraction of palpable bands in canine muscle. Ten pairs of biopsies were excised from gracilis and semitendinosus muscles of 4 mongrel dogs. These were compared with the histological findings reported in painful spots and muscle hardenings of human muscles. Test biopsies sampled a palpable band. Paired control biopsies sampled a portion of the same muscle where it showed no palpable hardening. Processed sections were randomized and read blind. Sections stained with aqueous toluidine blue showed no convincing metachromasia. Sections stained with trichrome showed no proliferation of endomysial connective tissue. Test sections stained with hematoxylin and eosin showed no proliferation of nuclei and no increase in the number of central nuclei in muscle fibers compared to control sections. No convincing histological difference was found. During surgery under Nembutal anesthesia, rubbing palpation of the exposed muscle elicited a transient contraction of a bundle of muscle fibers several milli-meters in diameter. This corresponded in time and position to the palpable band in the dog muscle. The band-like hardness palpated in these canine muscles appears to be caused by a circumscribed transient muscular contraction rather than histologically demonstrable structural changes."} {"id": "PMID:1266957", "title": "Interaction of gastrin I, secretin, and cholecystokinin on gallbladder smooth muscle.", "content": "The effect of cholecystokinin (CCK), the octapeptide of cholecystokinin (CCK-OP), gastrin I, and secretin was studied on guinea pig gallbladder smooth muscle in vitro. Both CCK and CCK-OP stimulated gallbladder contraction, with CCK-OP being more potent. Gastrin I, over a wide dose range, had no effect on gallbladder contractility. Secretin alone also showed no effect on gallbladder smooth muscle but in combination with CCK-OP it produced a noncompetitive type of inhibition. Michaelis-Menten kinetics showed the calculated maximum response of the secretin plus CCK-OP interaction to be less than with CCK-OP alone. There was no change in the dose required to achieve half-maximal response, D50. These studies indicate that: a) CCK-OP has a greater effect on gallbladder contractility than CCK, b) gastrin I has no effect on gallbladder muscle tone, and c) secretin acts as a noncompetitive antagonist of CCK-OP. These findings suggest that gallbladder motor function may be determined in part by the interaction of secretin and CCK rather than solely in response to CCK.", "contents": "Interaction of gastrin I, secretin, and cholecystokinin on gallbladder smooth muscle. The effect of cholecystokinin (CCK), the octapeptide of cholecystokinin (CCK-OP), gastrin I, and secretin was studied on guinea pig gallbladder smooth muscle in vitro. Both CCK and CCK-OP stimulated gallbladder contraction, with CCK-OP being more potent. Gastrin I, over a wide dose range, had no effect on gallbladder contractility. Secretin alone also showed no effect on gallbladder smooth muscle but in combination with CCK-OP it produced a noncompetitive type of inhibition. Michaelis-Menten kinetics showed the calculated maximum response of the secretin plus CCK-OP interaction to be less than with CCK-OP alone. There was no change in the dose required to achieve half-maximal response, D50. These studies indicate that: a) CCK-OP has a greater effect on gallbladder contractility than CCK, b) gastrin I has no effect on gallbladder muscle tone, and c) secretin acts as a noncompetitive antagonist of CCK-OP. These findings suggest that gallbladder motor function may be determined in part by the interaction of secretin and CCK rather than solely in response to CCK."} {"id": "PMID:1266958", "title": "Reflex limb dilatation following norepinephrine and angiotensin II in conscious dogs.", "content": "Effects of intravenous and intra-arterial norepinephrine (NE) and angiotensin II (AN) were compared in 18 conscious dogs instrumented with Doppler or electromagnetic flow probes on the iliac, mesenteric, and renal arteries, and catheters in the aorta and iliac arteries. NE and AN administered intravenously constricted the mesenteric and renal beds, and constricted the iliac bed when administered directly into the iliac artery. In contrast, intravenous NE and AN caused striking reflex increases in iliac flow and reductions in iliac resistance, respectively, in 12 of 18 dogs studied. The reflex iliac dilatation was not prevented by beta blockade with propranolol, cholinergic blockade with atropine, or prostaglandin synthetase inhibition with indomethacin. However, the responses were abolished by either phentolamine, 1 mg/kv iv, or after local blockade of the limb with either phentolamine, 0.5 mg/kg, or with tripelennamine, 2 mg/kg. The dilatation was not prevented by either bilateral carotid sinus and aortic nerve section or by bilateral vagotomy alone, but was prevented by a combination of these procedures. Thus, intravenous NE and AN cause striking reflex iliac dilatation in the limb in the conscious dog; the afferent arc of this reflex involves both arterial baroreceptor and vagal pathways, while the efferent mechanism involves an interaction of alpha-adrenergic and histaminergic receptors.", "contents": "Reflex limb dilatation following norepinephrine and angiotensin II in conscious dogs. Effects of intravenous and intra-arterial norepinephrine (NE) and angiotensin II (AN) were compared in 18 conscious dogs instrumented with Doppler or electromagnetic flow probes on the iliac, mesenteric, and renal arteries, and catheters in the aorta and iliac arteries. NE and AN administered intravenously constricted the mesenteric and renal beds, and constricted the iliac bed when administered directly into the iliac artery. In contrast, intravenous NE and AN caused striking reflex increases in iliac flow and reductions in iliac resistance, respectively, in 12 of 18 dogs studied. The reflex iliac dilatation was not prevented by beta blockade with propranolol, cholinergic blockade with atropine, or prostaglandin synthetase inhibition with indomethacin. However, the responses were abolished by either phentolamine, 1 mg/kv iv, or after local blockade of the limb with either phentolamine, 0.5 mg/kg, or with tripelennamine, 2 mg/kg. The dilatation was not prevented by either bilateral carotid sinus and aortic nerve section or by bilateral vagotomy alone, but was prevented by a combination of these procedures. Thus, intravenous NE and AN cause striking reflex iliac dilatation in the limb in the conscious dog; the afferent arc of this reflex involves both arterial baroreceptor and vagal pathways, while the efferent mechanism involves an interaction of alpha-adrenergic and histaminergic receptors."} {"id": "PMID:1266959", "title": "Norepinephrine turnover in heart and spleen of 7-, 22-, and 34 degree C-acclimated hamsters.", "content": "Norepinephrine (NE) turnover rates were measured in hamster (Mesocricetus auratus) heart and spleen tissues after 7-10 wk exposure to 7, 22, and 34 degrees C. The competitive inhibitor of NE synthesis, alpha-methyl-p-tyrosine methyl ester, was injected (200 mg/kg, ip) into acclimated animals. At sequential periods after drug treatment, hamsters were sacrificied by cervical transection, and tissues were removed and frozen. Rate constants, turnover time, and turnover rates were determined from regression analysis of NE tissue decay. Heart NE turnover was highest in cold-acclimated and lowest in heat-exposed animals (.111 and .047 mug/g per h, respectively), control values being intermediate (.081 mug/g per h). NE turnover is inversely related to tissue levels in the myocardium of temperature-acclimated hamsters. Spleen NE turnover was lowest with heat exposure, but spleen tissue levels of NE with heat or cold exposure were not different from control (22 degrees C) measurements. Heat-acclimated hamsters are slightly hyperthermic (Tre, 37.24 +/- .18 C; P, .032) compared to 22 degrees C-maintained controls (Tre, 36.85 +/- .07), but body temperature were unchanged with 7 degrees C exposure. The implication of altered NE synthesis is that sympathetic nerve activity is decreased with heat acclimation and increased with cold acclimation.", "contents": "Norepinephrine turnover in heart and spleen of 7-, 22-, and 34 degree C-acclimated hamsters. Norepinephrine (NE) turnover rates were measured in hamster (Mesocricetus auratus) heart and spleen tissues after 7-10 wk exposure to 7, 22, and 34 degrees C. The competitive inhibitor of NE synthesis, alpha-methyl-p-tyrosine methyl ester, was injected (200 mg/kg, ip) into acclimated animals. At sequential periods after drug treatment, hamsters were sacrificied by cervical transection, and tissues were removed and frozen. Rate constants, turnover time, and turnover rates were determined from regression analysis of NE tissue decay. Heart NE turnover was highest in cold-acclimated and lowest in heat-exposed animals (.111 and .047 mug/g per h, respectively), control values being intermediate (.081 mug/g per h). NE turnover is inversely related to tissue levels in the myocardium of temperature-acclimated hamsters. Spleen NE turnover was lowest with heat exposure, but spleen tissue levels of NE with heat or cold exposure were not different from control (22 degrees C) measurements. Heat-acclimated hamsters are slightly hyperthermic (Tre, 37.24 +/- .18 C; P, .032) compared to 22 degrees C-maintained controls (Tre, 36.85 +/- .07), but body temperature were unchanged with 7 degrees C exposure. The implication of altered NE synthesis is that sympathetic nerve activity is decreased with heat acclimation and increased with cold acclimation."} {"id": "PMID:1266960", "title": "Mechanisms of blood vessel constriction during hemorrhage.", "content": "The contributions of sympathetic nerves, circulating hormones, and passive vascular recoil to vasoconstriction and transcapillary fluid reabsorption in skin and skeletal muscle were examined in the forelegs of 55 pentobarbitalized dogs by using a combined gravimetric and segmental resistance technique. Hemorrhage elicited large increases in forelimb segmental vascular resistances and in the rate of extravascular fluid reabsorption. Only a small part of these responses could be attributed to the passive effects of reducing forelimb perfusion pressure.", "contents": "Mechanisms of blood vessel constriction during hemorrhage. The contributions of sympathetic nerves, circulating hormones, and passive vascular recoil to vasoconstriction and transcapillary fluid reabsorption in skin and skeletal muscle were examined in the forelegs of 55 pentobarbitalized dogs by using a combined gravimetric and segmental resistance technique. Hemorrhage elicited large increases in forelimb segmental vascular resistances and in the rate of extravascular fluid reabsorption. Only a small part of these responses could be attributed to the passive effects of reducing forelimb perfusion pressure."} {"id": "PMID:1266961", "title": "Localization of mesenteric hyperemia during digestion in dogs.", "content": "For localization of the site of post-prandial mesenteric hyperemia, low-fat, low-protein food was placed in either the stomach, duodenum, or jejunum while blood flow was measured in the celiac artery, superior mesenteric artery (SMA), or jejunal vein of anesthetized dogs. Distribution of flow in the jejunal wall was also measured. After intragastric placement of food, celiac arterial flow increased within 5 min and remained elevated for 30-60 min; SMA flow increased within 30 min and stayed up for at least 3 h. Intra-duodenal infusion of digested food increased SMA flow but did not alter celiac flow or flow to an isolated jejunal segment. Placement of digested food into one jejunal segment increased flow to that segment did not affect flow was localized to the mucosal layer. These studies indicate that during digestion, blood flow increases in the mucosa of the intestine when exposed to chyme and is not changed in other areas of the gastrointestinal tract. Postprandial mesenteric hyperemia induced by low-fat, low-protein food is a local phenomenon.", "contents": "Localization of mesenteric hyperemia during digestion in dogs. For localization of the site of post-prandial mesenteric hyperemia, low-fat, low-protein food was placed in either the stomach, duodenum, or jejunum while blood flow was measured in the celiac artery, superior mesenteric artery (SMA), or jejunal vein of anesthetized dogs. Distribution of flow in the jejunal wall was also measured. After intragastric placement of food, celiac arterial flow increased within 5 min and remained elevated for 30-60 min; SMA flow increased within 30 min and stayed up for at least 3 h. Intra-duodenal infusion of digested food increased SMA flow but did not alter celiac flow or flow to an isolated jejunal segment. Placement of digested food into one jejunal segment increased flow to that segment did not affect flow was localized to the mucosal layer. These studies indicate that during digestion, blood flow increases in the mucosa of the intestine when exposed to chyme and is not changed in other areas of the gastrointestinal tract. Postprandial mesenteric hyperemia induced by low-fat, low-protein food is a local phenomenon."} {"id": "PMID:1266962", "title": "Vascular response to short-term systemic hypoxia, hypercapnia, and asphyxia in the cat.", "content": "Acute systemic hypoxia, hypercapnia, or asphyxia was produced in ketamine-anesthetized, paralyzed cats by ventilating them for 2-4 min with appropriate gas mixtures. A sustained rise in arterial pressure occurred in all cases. Vascular responses to hypoxia (7% O2, 10% 02, or 14% O2) included muscle constriction, cutaneous (hindpaw) dilatation (no change with 14% O2), renal constriction (unchanged flow), and unchanged intestinal resistance. Asphyxia (hypoxia + 10% CO2) produced a similar pattern, except that intestinal dilatation occurred. Hypercapnia (10% CO2 + 21% O2) produced muscle constriction, renal constriction (unchanged flow), intestinal dilatation, and no change in cutaneous resistance. Intestinal dilatation seemed in all cases a response to elevated CO2 only. Hypercapnia augmented the effects of hypoxia in skin and skeletal muscle. The variation of responses in different vascular beds suggests a patterning of sympathetic discharge, and varying responsivity to local and humoral factors.", "contents": "Vascular response to short-term systemic hypoxia, hypercapnia, and asphyxia in the cat. Acute systemic hypoxia, hypercapnia, or asphyxia was produced in ketamine-anesthetized, paralyzed cats by ventilating them for 2-4 min with appropriate gas mixtures. A sustained rise in arterial pressure occurred in all cases. Vascular responses to hypoxia (7% O2, 10% 02, or 14% O2) included muscle constriction, cutaneous (hindpaw) dilatation (no change with 14% O2), renal constriction (unchanged flow), and unchanged intestinal resistance. Asphyxia (hypoxia + 10% CO2) produced a similar pattern, except that intestinal dilatation occurred. Hypercapnia (10% CO2 + 21% O2) produced muscle constriction, renal constriction (unchanged flow), intestinal dilatation, and no change in cutaneous resistance. Intestinal dilatation seemed in all cases a response to elevated CO2 only. Hypercapnia augmented the effects of hypoxia in skin and skeletal muscle. The variation of responses in different vascular beds suggests a patterning of sympathetic discharge, and varying responsivity to local and humoral factors."} {"id": "PMID:1266963", "title": "Beta-hydroxybutyrate transport in rat brain: developmental and dietary modulations.", "content": "Transport of beta-hydroxybutyrate (betaHB) into rat brain was estimated from the early rise in brain/serum 14C ratio after subcutaneous injection of [14C]betaHB. Permeability of the D isomer exceeded that of the L isomer. Permeability of either isomer rose throughout suckling (sevenfold) and declined after weaning to the low, newborn values. This age dependence differed markedly from those of cerebral blood flow and cerebral permeabilities of urea, glucose, valine, leucine, and DMO (5,5-dimethyloxazolidine-2,4-dione). Fat-feeding more than doubled cerebral betaHB permeability without significantly affecting cerebral blood flow or the permeabilities of urea, glucose, and DMO. Temperature dependence of betaHB permeability was similar to that of glucose transport. The age and diet dependence of betaHB were not accounted for in terms of body temperature, capillary surface, capillary porosity, or plasma proton concentration. A modulable betaHB carrier seemed indicated. Utilization of betaHB by the brain was signficantly governed by permeability, hence the increased permeability in ketotoc states should contribute to glucose sparing and eventually to protein sparing.", "contents": "Beta-hydroxybutyrate transport in rat brain: developmental and dietary modulations. Transport of beta-hydroxybutyrate (betaHB) into rat brain was estimated from the early rise in brain/serum 14C ratio after subcutaneous injection of [14C]betaHB. Permeability of the D isomer exceeded that of the L isomer. Permeability of either isomer rose throughout suckling (sevenfold) and declined after weaning to the low, newborn values. This age dependence differed markedly from those of cerebral blood flow and cerebral permeabilities of urea, glucose, valine, leucine, and DMO (5,5-dimethyloxazolidine-2,4-dione). Fat-feeding more than doubled cerebral betaHB permeability without significantly affecting cerebral blood flow or the permeabilities of urea, glucose, and DMO. Temperature dependence of betaHB permeability was similar to that of glucose transport. The age and diet dependence of betaHB were not accounted for in terms of body temperature, capillary surface, capillary porosity, or plasma proton concentration. A modulable betaHB carrier seemed indicated. Utilization of betaHB by the brain was signficantly governed by permeability, hence the increased permeability in ketotoc states should contribute to glucose sparing and eventually to protein sparing."} {"id": "PMID:1266964", "title": "Frequency-force relationships of mammalian ventricular muscle in vivo and in vitro.", "content": "The change in contractility with increasing heart rate was studied in the left ventricle of dogs and in isolated trabeculae carneae of cats. For some of the studies in situ a transient isovolumic state was created by aortic occlusion. At physiological temperatures the frequency-force relationship is flatter than at room temperature and at the same temperature it is flatter in vivo than in vitro. The frequency-(dF/dt)max relationship is steeper than the frequency-force relationship at both temperatures in vivo and in vitro. The frequency-(dF/dt)max relationship is steeper in vitro than it is in situ, although the discrepancy is less marked than in the case of the frequency-force relationship. It is concluded that \"staircase\" plays less of a physiological role in adjustment of contractile state in situ than might be inferred from studies of isolated tissue.", "contents": "Frequency-force relationships of mammalian ventricular muscle in vivo and in vitro. The change in contractility with increasing heart rate was studied in the left ventricle of dogs and in isolated trabeculae carneae of cats. For some of the studies in situ a transient isovolumic state was created by aortic occlusion. At physiological temperatures the frequency-force relationship is flatter than at room temperature and at the same temperature it is flatter in vivo than in vitro. The frequency-(dF/dt)max relationship is steeper than the frequency-force relationship at both temperatures in vivo and in vitro. The frequency-(dF/dt)max relationship is steeper in vitro than it is in situ, although the discrepancy is less marked than in the case of the frequency-force relationship. It is concluded that \"staircase\" plays less of a physiological role in adjustment of contractile state in situ than might be inferred from studies of isolated tissue."} {"id": "PMID:1266965", "title": "Propranolol and pyrogen effects of shivering and nonshivering thermogenesis in rats.", "content": "Injection of bacterial endotoxin (Piromen) into unanesthetized rats elicited increases in shivering and nonshivering thermogenesis as well as in colonic temperature. In animals exposed to 24-25 degrees C, treatment with propranolol (a beta-adrenergic antagonist) markedly diminished the pyrogen-induced increases in oxygen consumption (heat production) and colonic temperature with little change occurring in shivering activity. In contrast, in rats exposed to mild cold (17-18 degrees C), propranolol did not significantly alter the magnitude of the pyrogen-evoked thermogenesis. Rather in these animals, shivering tended to increase when nonshivering thermogenesis was blocked. These data are interpreted as reflecting differential effects of pyrogen on the pathways controlling the two modes of heat production in the rat.", "contents": "Propranolol and pyrogen effects of shivering and nonshivering thermogenesis in rats. Injection of bacterial endotoxin (Piromen) into unanesthetized rats elicited increases in shivering and nonshivering thermogenesis as well as in colonic temperature. In animals exposed to 24-25 degrees C, treatment with propranolol (a beta-adrenergic antagonist) markedly diminished the pyrogen-induced increases in oxygen consumption (heat production) and colonic temperature with little change occurring in shivering activity. In contrast, in rats exposed to mild cold (17-18 degrees C), propranolol did not significantly alter the magnitude of the pyrogen-evoked thermogenesis. Rather in these animals, shivering tended to increase when nonshivering thermogenesis was blocked. These data are interpreted as reflecting differential effects of pyrogen on the pathways controlling the two modes of heat production in the rat."} {"id": "PMID:1266966", "title": "Uptake and metabolism of beta-alanine and L-carnosine by rat tissues in vitro: role in nutrition.", "content": "Uptake and metabolism of the dipeptide L-carnosine (beta-alanyl-L-histidine) and of the free amino acid beta-alanine were studied in scraped mucosal epithelium of jejunum, kidney cortex slices, and intact hemidiaphragm muscle of the rat. These preparations expose plasma membranes with various orientations to amino nitrogen nutrition.", "contents": "Uptake and metabolism of beta-alanine and L-carnosine by rat tissues in vitro: role in nutrition. Uptake and metabolism of the dipeptide L-carnosine (beta-alanyl-L-histidine) and of the free amino acid beta-alanine were studied in scraped mucosal epithelium of jejunum, kidney cortex slices, and intact hemidiaphragm muscle of the rat. These preparations expose plasma membranes with various orientations to amino nitrogen nutrition."} {"id": "PMID:1266967", "title": "Effects of anesthetic agents on autoregulation of renal hemodynamics in the rat and dog.", "content": "Controversy has existed over apparent dissimilarities in the autoregulatory capacities of the rat and dog. A protocol was designed to evaluate both the effects of the anesthetic agents. Nembutal (used most commonly in dogs) and Inactin (most frequently employed in rats) and the species peculiarities of these two mammals on autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). With Nembutal autoregulation of RBF was present in both experimental animals. Inactin impaired RBF autoregulation similarly in both species. With impaired RBF autoregulation similarly in both species. With either anesthetic GFR was autoregulated well in both rat and dog. Comparison of the two species revealed a greater RBF per gram kidney weight and a higher renal perfusion pressure (RPP) at which autoregulation of both hemodynamic parameters was lost in the rat. It is concluded from these studies that 1) the frequent use of Inactin in the rat in large part accounts for the observed lack of autoregulation of RBF in this animal and 2) renal hemodynamic responses are qualitatively similar in rat and dog when the same anesthetic agents are used.", "contents": "Effects of anesthetic agents on autoregulation of renal hemodynamics in the rat and dog. Controversy has existed over apparent dissimilarities in the autoregulatory capacities of the rat and dog. A protocol was designed to evaluate both the effects of the anesthetic agents. Nembutal (used most commonly in dogs) and Inactin (most frequently employed in rats) and the species peculiarities of these two mammals on autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR). With Nembutal autoregulation of RBF was present in both experimental animals. Inactin impaired RBF autoregulation similarly in both species. With impaired RBF autoregulation similarly in both species. With either anesthetic GFR was autoregulated well in both rat and dog. Comparison of the two species revealed a greater RBF per gram kidney weight and a higher renal perfusion pressure (RPP) at which autoregulation of both hemodynamic parameters was lost in the rat. It is concluded from these studies that 1) the frequent use of Inactin in the rat in large part accounts for the observed lack of autoregulation of RBF in this animal and 2) renal hemodynamic responses are qualitatively similar in rat and dog when the same anesthetic agents are used."} {"id": "PMID:1266968", "title": "Metabolic response to carbon monoxide by isolated rat lungs.", "content": "Glucose metabolism was studied in isolated rat lungs ventilated with 95% O2.5% CO2 (control), 95% N2: 5% CO2 (hypoxia), and 95% CO:5% CO2 (carbon monoxide) and perfused for 100-120 min with Krebs-Ringer-bicarbonate buffer, pH 7.4, containing [U-14C] and [3-3H]glucose. The production of 14C-labeled lactate plus pyruvate (L + P) and of 14CO2 represented 48% and 22% respectively, of the total [14C]glucose utilization. The lactate-to-pyruvate ratio (L/P) was 8.7. Tritium was recovered predominantly as 3H2O in the perfusate. Wth carbon monoxide ventilation, L + P production was increased by 357% with an L/P of 52.9, and 14CO2 production was markedly decreased. A 56% decrease in lung ATP content was associated with decreased incorporation of 14C into fatty acids. Compared with CO, changes with N2 ventilation were less marked, indicating that ventilation with CO is a more effective method with which to study inhibtion of oxidative metabolism. The lung exhibits a Pasteur effectbintain ATP content or its supply for synthetic activity.", "contents": "Metabolic response to carbon monoxide by isolated rat lungs. Glucose metabolism was studied in isolated rat lungs ventilated with 95% O2.5% CO2 (control), 95% N2: 5% CO2 (hypoxia), and 95% CO:5% CO2 (carbon monoxide) and perfused for 100-120 min with Krebs-Ringer-bicarbonate buffer, pH 7.4, containing [U-14C] and [3-3H]glucose. The production of 14C-labeled lactate plus pyruvate (L + P) and of 14CO2 represented 48% and 22% respectively, of the total [14C]glucose utilization. The lactate-to-pyruvate ratio (L/P) was 8.7. Tritium was recovered predominantly as 3H2O in the perfusate. Wth carbon monoxide ventilation, L + P production was increased by 357% with an L/P of 52.9, and 14CO2 production was markedly decreased. A 56% decrease in lung ATP content was associated with decreased incorporation of 14C into fatty acids. Compared with CO, changes with N2 ventilation were less marked, indicating that ventilation with CO is a more effective method with which to study inhibtion of oxidative metabolism. The lung exhibits a Pasteur effectbintain ATP content or its supply for synthetic activity."} {"id": "PMID:1266969", "title": "Modification of aortic barorecptor resetting in the spontaneously hypertensive rat.", "content": "Aortic barorecptor function was studied in spontaneously hypertensive rats (SHR) of various ages and normotensive Wistar rats. The aortic arch was isolated and perfused, and the activity of the left aortic nerve was recorded. The threshold pressure to elicit barerecptor firing was 80-120 mmHg in normotensive Wistar rats. Resetting of barorecptors (threshold pressure 160-180 mmHg) was found in all untreated SHR of 35-70 wk of age. Resetting of barorecptors was prevented in SHR by starting treatment with antihypertensive agents at the age of 11 wk. Treatment of 32-wk old SHR with antihypertensive agents for 4-6 wk resulted in reversal of barorecptor resetting in 50% animals. The percentage of SHR showing complete reversal of resetting did not increase even when the duration of treatment was tripled. In 52- to 64-wk old SHR, treated with antihypertensive agents, reversal of baroceptor resetting was seen in only 30% animals. It was concluded that baroceptor resetting in SHR was secondary to hypertension. Hypertension, in turn, induced hypertrophy of the tunica media of the aorta. Histological studies showed a close correlation between aortic hypertrophy resetting. Aortic hypertrophy may, therefore, be one of the important factors involved in baroceptor resetting.", "contents": "Modification of aortic barorecptor resetting in the spontaneously hypertensive rat. Aortic barorecptor function was studied in spontaneously hypertensive rats (SHR) of various ages and normotensive Wistar rats. The aortic arch was isolated and perfused, and the activity of the left aortic nerve was recorded. The threshold pressure to elicit barerecptor firing was 80-120 mmHg in normotensive Wistar rats. Resetting of barorecptors (threshold pressure 160-180 mmHg) was found in all untreated SHR of 35-70 wk of age. Resetting of barorecptors was prevented in SHR by starting treatment with antihypertensive agents at the age of 11 wk. Treatment of 32-wk old SHR with antihypertensive agents for 4-6 wk resulted in reversal of barorecptor resetting in 50% animals. The percentage of SHR showing complete reversal of resetting did not increase even when the duration of treatment was tripled. In 52- to 64-wk old SHR, treated with antihypertensive agents, reversal of baroceptor resetting was seen in only 30% animals. It was concluded that baroceptor resetting in SHR was secondary to hypertension. Hypertension, in turn, induced hypertrophy of the tunica media of the aorta. Histological studies showed a close correlation between aortic hypertrophy resetting. Aortic hypertrophy may, therefore, be one of the important factors involved in baroceptor resetting."} {"id": "PMID:1266970", "title": "Release of prostaglandin F2alpha during splanchnic artery occlusion shock.", "content": "Prostaglandin F2alpha concentrations were determined in hepatic portal venous plasma of dogs during splanchnic artery occlusion (SAO) shock and in nonshock control dogs. Dogs subjected to SAO shock exhibited a dramatic decrease in mean arterial blood pressure and significant increases in portal venous PGF2alpha and amino-nitrogen concentrations, as well as in cathepsin D and MDF activities. Dogs treated with indomethacin prior to SAO shock did not exhibit a significant increase in portal venous PGF2alpha. Indomethacin had no effect on the increase of plasma amino-nitrogen and only slightly reduced portal venous cathepsin D activity during SAO shock. Nevertheless, indomethacin significantly attenuated the severity of the postrelease hypotension observed in SAO shock and diminished the plasma accumulation of MDF. These studies indicate that prostaglandins are released from the splanchnic region during SAO shock and that this release can be prevented by pretreatment with indomethacin. The role of endogenously released prostaglandins in SAO shock is not clear, but the magnitude of the increase warrants further study.", "contents": "Release of prostaglandin F2alpha during splanchnic artery occlusion shock. Prostaglandin F2alpha concentrations were determined in hepatic portal venous plasma of dogs during splanchnic artery occlusion (SAO) shock and in nonshock control dogs. Dogs subjected to SAO shock exhibited a dramatic decrease in mean arterial blood pressure and significant increases in portal venous PGF2alpha and amino-nitrogen concentrations, as well as in cathepsin D and MDF activities. Dogs treated with indomethacin prior to SAO shock did not exhibit a significant increase in portal venous PGF2alpha. Indomethacin had no effect on the increase of plasma amino-nitrogen and only slightly reduced portal venous cathepsin D activity during SAO shock. Nevertheless, indomethacin significantly attenuated the severity of the postrelease hypotension observed in SAO shock and diminished the plasma accumulation of MDF. These studies indicate that prostaglandins are released from the splanchnic region during SAO shock and that this release can be prevented by pretreatment with indomethacin. The role of endogenously released prostaglandins in SAO shock is not clear, but the magnitude of the increase warrants further study."} {"id": "PMID:1266971", "title": "Regional blood flow in normotensive and spontaneously hypertensive rats.", "content": "Regional distribution of cardiac output in unanesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar NR male rats (10 each group; average age 21 wk) was determined using two 15-mum microspheres (141Ce and 85Sr) injected 10 min apart through a left ventricular (LV) cannula. Fractional flow distribution was expressed as percentage activity of injected dose (average of the two measurements). Despite differences in body and organ weights, organ flow distribution did not vary between SHR and WKY, except for heart and testes (P less than 0.025). However, differences did not exist between SHR and NR with respect to heart, brain, lungs, spleen, and adrenal flows (P less than 0.05).", "contents": "Regional blood flow in normotensive and spontaneously hypertensive rats. Regional distribution of cardiac output in unanesthetized spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) and Wistar NR male rats (10 each group; average age 21 wk) was determined using two 15-mum microspheres (141Ce and 85Sr) injected 10 min apart through a left ventricular (LV) cannula. Fractional flow distribution was expressed as percentage activity of injected dose (average of the two measurements). Despite differences in body and organ weights, organ flow distribution did not vary between SHR and WKY, except for heart and testes (P less than 0.025). However, differences did not exist between SHR and NR with respect to heart, brain, lungs, spleen, and adrenal flows (P less than 0.05)."} {"id": "PMID:1266972", "title": "Role of distal delivery of filtrate in impaired renal dilution of the hypothyroid rat.", "content": "Free water clearance (CH2O) was measured during hypotonic saline infusion in Sprague-Dawley and in Brattleboro (DI) rats with 131I-induced hypothyroidism and their age-matched controls. At peak urine flow, which was similar in hypothyroid DI (HDI) and control DI (CDI) rats, inulin clearance (CIn/kg) and CH2O/kg were 23 and 20% (P less than 0.02) lower in HDI. Fractional urine flow and fractional sodium excretion were 30 and 40% (P less than 0.001) higher in HDI. Utilization of distal delivery of filtrate for CH2O, formation was 16% less in HDI (P less than 0.01). Papillary osmolality was not higher in HDI rats. Data in Sprague-Dawley rats were similar to those of the DI rats, indicating that endogenous ADH was effectively suppressed. It is concluded: 1) delivery of filtrate out of the proximal tubule was not diminished in hypothyroid rats in spite of a decrease in CIn; 2) despite a similar delivery of filtrate to the distal diluting site, CH2O formation was less in hypothyroid rats than in controls; 3) these data suggest that a defect in the diluting segment could be unmasked at high rates of filtrate delivered to the distal nephron; 4) this defect could be either due to impaired sodium chloride reabsorption or due to increased backdiffusion of water in the distal nephron.", "contents": "Role of distal delivery of filtrate in impaired renal dilution of the hypothyroid rat. Free water clearance (CH2O) was measured during hypotonic saline infusion in Sprague-Dawley and in Brattleboro (DI) rats with 131I-induced hypothyroidism and their age-matched controls. At peak urine flow, which was similar in hypothyroid DI (HDI) and control DI (CDI) rats, inulin clearance (CIn/kg) and CH2O/kg were 23 and 20% (P less than 0.02) lower in HDI. Fractional urine flow and fractional sodium excretion were 30 and 40% (P less than 0.001) higher in HDI. Utilization of distal delivery of filtrate for CH2O, formation was 16% less in HDI (P less than 0.01). Papillary osmolality was not higher in HDI rats. Data in Sprague-Dawley rats were similar to those of the DI rats, indicating that endogenous ADH was effectively suppressed. It is concluded: 1) delivery of filtrate out of the proximal tubule was not diminished in hypothyroid rats in spite of a decrease in CIn; 2) despite a similar delivery of filtrate to the distal diluting site, CH2O formation was less in hypothyroid rats than in controls; 3) these data suggest that a defect in the diluting segment could be unmasked at high rates of filtrate delivered to the distal nephron; 4) this defect could be either due to impaired sodium chloride reabsorption or due to increased backdiffusion of water in the distal nephron."} {"id": "PMID:1266973", "title": "Placental amino acid uptake. III. Transport systems for neutral amino acids.", "content": "The human placenta is known to concentrate nearly all amino acids intracellularly for transfer to the fetus. To clarify the mechanism and regulation of this process we have determined the specificity of the principal placental transport systems for neutral amino acids. With the use of competitive inhibition techniques, three transport systems of overlapping specificity have been elucidated. These correspond approximately to the \"A\", \"L\", and \"ASC\" systems of Christensen and associates. In the placenta the specificity of these systems is as follows: A system - alpha aminoisobutyric acid (AIB), glycine, proline, N-methylalanine, alanine, serine, threonine, and glutamine; L system - isoleucine, valine, phenylalanine, BCH, alanine, serine, threonine, and glutamine; and ASC system - alanine, serine, threonine, and glutamine. Placental AIB uptake previously has been shown to increase with preincubation of tissue in vitro. This increase has now been found to be limited to the A system. Activity of the other two systems is essentially unaffected, demonstrating that the transport pathways are separately regulated.", "contents": "Placental amino acid uptake. III. Transport systems for neutral amino acids. The human placenta is known to concentrate nearly all amino acids intracellularly for transfer to the fetus. To clarify the mechanism and regulation of this process we have determined the specificity of the principal placental transport systems for neutral amino acids. With the use of competitive inhibition techniques, three transport systems of overlapping specificity have been elucidated. These correspond approximately to the \"A\", \"L\", and \"ASC\" systems of Christensen and associates. In the placenta the specificity of these systems is as follows: A system - alpha aminoisobutyric acid (AIB), glycine, proline, N-methylalanine, alanine, serine, threonine, and glutamine; L system - isoleucine, valine, phenylalanine, BCH, alanine, serine, threonine, and glutamine; and ASC system - alanine, serine, threonine, and glutamine. Placental AIB uptake previously has been shown to increase with preincubation of tissue in vitro. This increase has now been found to be limited to the A system. Activity of the other two systems is essentially unaffected, demonstrating that the transport pathways are separately regulated."} {"id": "PMID:1266974", "title": "Renal effect of meclofenamate in presence and absence of superfusion bioassay.", "content": "Systemic blood pressure (SBP), renal blood flow (RBF), renal vascular resistance (RVR), and arterial and renal venous prostaglandin E (PGE) concentrations were determined in pentobarbital-anesthetized dogs.The effect of sodium meclofenamate infused into the renal artery was compared under two sets of conditions. In experiments carried out under control conditions, SBP, RBF, and RVR were stable and meclofenamate caused only a slight decrease in RBF (5.4%) and increase in RVR.", "contents": "Renal effect of meclofenamate in presence and absence of superfusion bioassay. Systemic blood pressure (SBP), renal blood flow (RBF), renal vascular resistance (RVR), and arterial and renal venous prostaglandin E (PGE) concentrations were determined in pentobarbital-anesthetized dogs.The effect of sodium meclofenamate infused into the renal artery was compared under two sets of conditions. In experiments carried out under control conditions, SBP, RBF, and RVR were stable and meclofenamate caused only a slight decrease in RBF (5.4%) and increase in RVR."} {"id": "PMID:1266975", "title": "Effect of occlusion duration on reactive hyperemia in sartorius muscle capillaries.", "content": "Reactive hyperemia was studied in cat sartorius muscle by measurement of venous outflow and capillary red cell velocity following occlusions of 5-120 s. The peak value for volume flow rose in a graded manner as occlusion duration increased, reaching a level of 280% above control following 120 s of occlusion. By contrast, peak values for capillary flow were 200% above control even after short (10-15 s) occlusions and increased moderately thereafter to 280% above control following 120-s occlusions.", "contents": "Effect of occlusion duration on reactive hyperemia in sartorius muscle capillaries. Reactive hyperemia was studied in cat sartorius muscle by measurement of venous outflow and capillary red cell velocity following occlusions of 5-120 s. The peak value for volume flow rose in a graded manner as occlusion duration increased, reaching a level of 280% above control following 120 s of occlusion. By contrast, peak values for capillary flow were 200% above control even after short (10-15 s) occlusions and increased moderately thereafter to 280% above control following 120-s occlusions."} {"id": "PMID:1266976", "title": "Nonshivering thermogenesis induced by repetitive cooling of spinal cord in the rat.", "content": "The effect of prolonged and repetitive cooling of the spinal cord on the sensitivity to the metabolic effect of exogenous noradrenaline and on the resistance to cold exposure was studied in the white male rat. The spinal cord of 10 animals was cooled for an average of 90 h-9 h/day 5 days/wk - to a level that induced an increase in oxygen uptake of almost 70%. Oxygen consumption was then measured at 30 degrees C before and 1 h after a subcutaneous injection of noradrenaline (0.4 mg/kg). Following the noradrenaline injection, the experimental animals increased oxygen uptake by 71%, while the control ones increased it by only 33% (P less than 0.01). During exposure to -20 degrees C, the experimental animals, despite their increased capacity for nonshivering thermogenesis, did not maintain rectal temperature longer than the control ones, thus showing that other factors also play a significant role in cold adaptation in the rat.", "contents": "Nonshivering thermogenesis induced by repetitive cooling of spinal cord in the rat. The effect of prolonged and repetitive cooling of the spinal cord on the sensitivity to the metabolic effect of exogenous noradrenaline and on the resistance to cold exposure was studied in the white male rat. The spinal cord of 10 animals was cooled for an average of 90 h-9 h/day 5 days/wk - to a level that induced an increase in oxygen uptake of almost 70%. Oxygen consumption was then measured at 30 degrees C before and 1 h after a subcutaneous injection of noradrenaline (0.4 mg/kg). Following the noradrenaline injection, the experimental animals increased oxygen uptake by 71%, while the control ones increased it by only 33% (P less than 0.01). During exposure to -20 degrees C, the experimental animals, despite their increased capacity for nonshivering thermogenesis, did not maintain rectal temperature longer than the control ones, thus showing that other factors also play a significant role in cold adaptation in the rat."} {"id": "PMID:1266977", "title": "Circadian rhythms of intestinal sucrase and glucose transport: cued by time of feeding.", "content": "In the rat, under constant illumination, the activities of the digestive enzyme sucrase and the absorptive transport system for glucose follow circadian rhythms on ad lib. and controlled feeding regimens. In response to controlled feeding, (1400-1800 h or 0200-0600 h, EST), both rhythms shift with time and the general level of activities are enhanced. Sucrase activity peaks before feeding and transport activity peaks during feeding. Feeding is a synchronizer for these digestive-absorptive functions, and the maximum activity of a function may occur prior to as well as subsequent to the daily onset of the synchronizer. The rhythms of these functions results from previous days' feeding patterns.", "contents": "Circadian rhythms of intestinal sucrase and glucose transport: cued by time of feeding. In the rat, under constant illumination, the activities of the digestive enzyme sucrase and the absorptive transport system for glucose follow circadian rhythms on ad lib. and controlled feeding regimens. In response to controlled feeding, (1400-1800 h or 0200-0600 h, EST), both rhythms shift with time and the general level of activities are enhanced. Sucrase activity peaks before feeding and transport activity peaks during feeding. Feeding is a synchronizer for these digestive-absorptive functions, and the maximum activity of a function may occur prior to as well as subsequent to the daily onset of the synchronizer. The rhythms of these functions results from previous days' feeding patterns."} {"id": "PMID:1266978", "title": "Effect of graded bilirubin loads on bilirubin transport by perfused rat liver.", "content": "Features of hepatic bilirubin transport were studied with the isolated perfused rat liver. Male Wistar rats weighing 350-400 g were used as liver donors. When bilirubin was constantly infused into the perfusion medium, which contained sheep erythrocytes and 3.0 g/100 ml bovine serum albumin, the maximal excretion rate for bilirubin was 14.4 +/- 1.2 mug/min per g liver. Over a wide range of constant bilirubin infusion rates which went as high as 25.9 mug/min per g liver, there was no effect on bile flow, bile acid excretion, or the pattern of bilirubin conjugates in bile. The hepatic extraction efficiency for unconjugated bilirubin from the perfusate also remained constant averaging 26%. However, when bolus injections of bilirubin were used to produce higher levels of unconjugated bilirubin in the perfusate than could be attained during constant infusion, the disappearance rate of [14C]bilirubin from the perfusate decreased with increasing bilirubin concentrations. This was consistent with saturation of the hepatic removal of unconjugated bilirubin.", "contents": "Effect of graded bilirubin loads on bilirubin transport by perfused rat liver. Features of hepatic bilirubin transport were studied with the isolated perfused rat liver. Male Wistar rats weighing 350-400 g were used as liver donors. When bilirubin was constantly infused into the perfusion medium, which contained sheep erythrocytes and 3.0 g/100 ml bovine serum albumin, the maximal excretion rate for bilirubin was 14.4 +/- 1.2 mug/min per g liver. Over a wide range of constant bilirubin infusion rates which went as high as 25.9 mug/min per g liver, there was no effect on bile flow, bile acid excretion, or the pattern of bilirubin conjugates in bile. The hepatic extraction efficiency for unconjugated bilirubin from the perfusate also remained constant averaging 26%. However, when bolus injections of bilirubin were used to produce higher levels of unconjugated bilirubin in the perfusate than could be attained during constant infusion, the disappearance rate of [14C]bilirubin from the perfusate decreased with increasing bilirubin concentrations. This was consistent with saturation of the hepatic removal of unconjugated bilirubin."} {"id": "PMID:1266979", "title": "Potassium flux in smooth muscle of frog stomach.", "content": "In frog stomach muscle fibers, normal steady-state K flux, estimated directly from 42K uptake, was 0.17 pmol/cm2 per s at 5 degrees C and 0.63 pmol/cm2 per s at 15 degrees C. Influx characteristics were studied at 5 degrees C, where backflux and diffusional delay effects are minimized. Steady-state K influx was a saturating function of external [K] over the range 0.25-11 mM [K]o; influx at normal and higher [K]o did not differ significantly. Na loading (in K-free or low K solution) strongly stimulated influx, which showed altered saturation kinetics; maximal K influx was a quasilinear function of internal [Na]. Ouabain (10(-4) M) reduced normal and stimulated K influx markedly. Ethacrynic acid (10(-3) M) caused net K loss and Na gain, but increased K influx fourfold; ouabain inhibited the stimulated influx by 50%. These results indicate that K influx depends mainly on cycling of the Na-K pump and is normally limited by Na efflux. Ethacrynic acid may stimulate another mode of pump operation, K-K exchange, and uncouple the normal operation.", "contents": "Potassium flux in smooth muscle of frog stomach. In frog stomach muscle fibers, normal steady-state K flux, estimated directly from 42K uptake, was 0.17 pmol/cm2 per s at 5 degrees C and 0.63 pmol/cm2 per s at 15 degrees C. Influx characteristics were studied at 5 degrees C, where backflux and diffusional delay effects are minimized. Steady-state K influx was a saturating function of external [K] over the range 0.25-11 mM [K]o; influx at normal and higher [K]o did not differ significantly. Na loading (in K-free or low K solution) strongly stimulated influx, which showed altered saturation kinetics; maximal K influx was a quasilinear function of internal [Na]. Ouabain (10(-4) M) reduced normal and stimulated K influx markedly. Ethacrynic acid (10(-3) M) caused net K loss and Na gain, but increased K influx fourfold; ouabain inhibited the stimulated influx by 50%. These results indicate that K influx depends mainly on cycling of the Na-K pump and is normally limited by Na efflux. Ethacrynic acid may stimulate another mode of pump operation, K-K exchange, and uncouple the normal operation."} {"id": "PMID:1266980", "title": "Disposition of plasma cholesterol in the pregnant hypocholesterolemic rabbit.", "content": "Processes that might explain the hypocholesterolemia observed in pregnant rabbits were studied in animals fed a cholesterol-free chow diet. Excretion of endogenous steroids, measured after administration of a single intravenous dose of radioactive cholesterol, averaged 75 mg/day in controls and 96 mg/day in pregnant hypocholesterolemic rabbits. The mass of maternal plasma cholesterol transferred to the fetuses was measured in animals in which a constant plasma cholesterol specific activity was maintained. Placental transfer during the first 28 days of gestation ranged from 2 to 12 mg/day for mothers carrying litters of one to eight fetuses. It is concluded that loss of maternal plasma cholesterol due to placental transfer is small compared to loss by fecal steroid excretion. Because large decreases in plasma cholesterol concentration during pregnancy and increases at parturition were not accompanied by changes in the slopes of the specific activity-time curves, it appears most likely that cholesterol in isotopic equilibrium with plasma cholesterol is temporarily and reversibly sequestered in maternal tissues of the pregnant rabbit.", "contents": "Disposition of plasma cholesterol in the pregnant hypocholesterolemic rabbit. Processes that might explain the hypocholesterolemia observed in pregnant rabbits were studied in animals fed a cholesterol-free chow diet. Excretion of endogenous steroids, measured after administration of a single intravenous dose of radioactive cholesterol, averaged 75 mg/day in controls and 96 mg/day in pregnant hypocholesterolemic rabbits. The mass of maternal plasma cholesterol transferred to the fetuses was measured in animals in which a constant plasma cholesterol specific activity was maintained. Placental transfer during the first 28 days of gestation ranged from 2 to 12 mg/day for mothers carrying litters of one to eight fetuses. It is concluded that loss of maternal plasma cholesterol due to placental transfer is small compared to loss by fecal steroid excretion. Because large decreases in plasma cholesterol concentration during pregnancy and increases at parturition were not accompanied by changes in the slopes of the specific activity-time curves, it appears most likely that cholesterol in isotopic equilibrium with plasma cholesterol is temporarily and reversibly sequestered in maternal tissues of the pregnant rabbit."} {"id": "PMID:1266981", "title": "Mechanism of action of aspirin on canine gastric mucosa.", "content": "Using an in vivo chambered canine stomach preparation, exposure of the gastric mucosa to 5, 10, and 20 mM aspirin(pH 3.0) resulted in a decrease in electrical potential difference (PD) and in an increase in resistance (R) within 30 min. In vitro, exposure of the mucosal side of the isolated canine gastric mucosa to 5, 10, and 20 mM aspirin (pH 3.0) for 1 h or of 1 mM aspirin (pH 3.0) for longer than 1 h resulted in marked permeability changes, i.e., increases in the undirectional fluxes of Na+ and Cl-, as well as inhibition of net ion fluxes. These concentrations of nonionized aspirin (pH 3.0) also reduced the R and PD. However, 1 mM aspirin (pH 3.0) or 20 mM ionized aspirin (pH 7.4) depresses the active transport of ion, increases R, but does not increase the ionic permeability. Mucosal adenosine triphosphate (ATP) content is reduced by mucosal instillation of aspirin (pH 3.0). These results demonstrate that the initial action of aspirin is inhibition of ion transport which is followed by an increase in permeability.", "contents": "Mechanism of action of aspirin on canine gastric mucosa. Using an in vivo chambered canine stomach preparation, exposure of the gastric mucosa to 5, 10, and 20 mM aspirin(pH 3.0) resulted in a decrease in electrical potential difference (PD) and in an increase in resistance (R) within 30 min. In vitro, exposure of the mucosal side of the isolated canine gastric mucosa to 5, 10, and 20 mM aspirin (pH 3.0) for 1 h or of 1 mM aspirin (pH 3.0) for longer than 1 h resulted in marked permeability changes, i.e., increases in the undirectional fluxes of Na+ and Cl-, as well as inhibition of net ion fluxes. These concentrations of nonionized aspirin (pH 3.0) also reduced the R and PD. However, 1 mM aspirin (pH 3.0) or 20 mM ionized aspirin (pH 7.4) depresses the active transport of ion, increases R, but does not increase the ionic permeability. Mucosal adenosine triphosphate (ATP) content is reduced by mucosal instillation of aspirin (pH 3.0). These results demonstrate that the initial action of aspirin is inhibition of ion transport which is followed by an increase in permeability."} {"id": "PMID:1266982", "title": "Renal excretion of uric acid in the rat: a micropuncture and microperfusion study.", "content": "Free-flow micropuncture experiments were done in rats of three strains infused with small amounts of urate [plasma urate (P urate) = 95 +/- 8 muM]. Urate concentrations in tubular fluid were measured by an accurate chemical fluorometric ultramicromethod. In fluid from surface glomeruli, the glomerular fluid-to-plasma urate ratio [GF/P) urate] was 0.99 +/- 0.03 (n=11), i.e., lower than expected for total ultrafiltrability of plasma urate. Along proximal convolutions, net reabsorption of 55% of filtered urate was demonstrated. Small amounts of urate may have been reabsorbed between late proximal and early distal sites. Net transepithelial movements of urate did not occur in distal tubules or collecting ducts. In microperfusion experiments on proximal tubules, both a reabsorptive flow of urate (loss of perfused [2-14C]urate) and a secretory flow (entrance of cold urate into perfusate) of the same order of magnitude were demonstrated. Neither flow was influenced by simultaneous water movements. Microperfusion of Henle's loops indicated a significant but very small net reabsorption.", "contents": "Renal excretion of uric acid in the rat: a micropuncture and microperfusion study. Free-flow micropuncture experiments were done in rats of three strains infused with small amounts of urate [plasma urate (P urate) = 95 +/- 8 muM]. Urate concentrations in tubular fluid were measured by an accurate chemical fluorometric ultramicromethod. In fluid from surface glomeruli, the glomerular fluid-to-plasma urate ratio [GF/P) urate] was 0.99 +/- 0.03 (n=11), i.e., lower than expected for total ultrafiltrability of plasma urate. Along proximal convolutions, net reabsorption of 55% of filtered urate was demonstrated. Small amounts of urate may have been reabsorbed between late proximal and early distal sites. Net transepithelial movements of urate did not occur in distal tubules or collecting ducts. In microperfusion experiments on proximal tubules, both a reabsorptive flow of urate (loss of perfused [2-14C]urate) and a secretory flow (entrance of cold urate into perfusate) of the same order of magnitude were demonstrated. Neither flow was influenced by simultaneous water movements. Microperfusion of Henle's loops indicated a significant but very small net reabsorption."} {"id": "PMID:1266983", "title": "Increase in renin release after sionaortic denervation and cervical vagotomy.", "content": "The role of the vagi in the control of renin secretion was investigated in dogs maintained on a high-salt diet. Renal perfusion pressure was maintained relatively constant by the manipulation of a suprarenal aortic snare. Mean arterial blood pressure (MAP), plasma renin activity (PRA), and packed cell volume (PCV) increased after sinoaortic denervation and cervical vagotomy. Cooling of cervical vagi to 3-5 degrees C had the same effect as vagotomy. There was no change in MAP, PRA, and PCV in sham-operated animals. Propranolol prevented the increase in PRA following sinoaortic denervation and vagotomy, but not that in MAP or PCV. In splenectomized dogs, PCV still showed increases after sinoaortic denervation and vagotomy. It is suggested that the removal of sinoaortic and/or vagal inhibitory effects on the vasomotor center causes increases in sympathetic discharge to the adrenal medulla and the peripheral vessels, and that this in turn leads to the increase in MAP. The increase in sympathetic discharge to the adrenal medulla and the kidney causes the increases in PRA.", "contents": "Increase in renin release after sionaortic denervation and cervical vagotomy. The role of the vagi in the control of renin secretion was investigated in dogs maintained on a high-salt diet. Renal perfusion pressure was maintained relatively constant by the manipulation of a suprarenal aortic snare. Mean arterial blood pressure (MAP), plasma renin activity (PRA), and packed cell volume (PCV) increased after sinoaortic denervation and cervical vagotomy. Cooling of cervical vagi to 3-5 degrees C had the same effect as vagotomy. There was no change in MAP, PRA, and PCV in sham-operated animals. Propranolol prevented the increase in PRA following sinoaortic denervation and vagotomy, but not that in MAP or PCV. In splenectomized dogs, PCV still showed increases after sinoaortic denervation and vagotomy. It is suggested that the removal of sinoaortic and/or vagal inhibitory effects on the vasomotor center causes increases in sympathetic discharge to the adrenal medulla and the peripheral vessels, and that this in turn leads to the increase in MAP. The increase in sympathetic discharge to the adrenal medulla and the kidney causes the increases in PRA."} {"id": "PMID:1266984", "title": "Intrarenal calcium in phosphate handling.", "content": "The intrarenal role of plasma ionized calcium (Ca), on fractional phosphate excretion (FE PO4) was investigated in dogs with control of parathyroid hormone (PTH). In series 1, acute thyroparathyroidectomy was immediately followed by a constant infusion of bovine PTH (0.01 U/kg per min). Subsequent calcium chloride infusions increased Cai in plasma phosphate and decreased in the percentage of ultrafiltrable phosphate. A 20% increase in Cai significantly increased FE PO4 by +3.82 +/- 0.97% (P less than 0.01) when infused intravenously and by +2.62 +/- 1.06% (P less than 0.05) when infused in the renal artery. In contrast, a 75% increase in Cai did not significantly change FE PO4. In series 2, dogs were thyroparathyroidectomized 18 h before experiments, and no PTH infusion was initiated. A bolus of bovine PTH (30 U/kg) increased FE PO4 + 8.9 +/- 0.9% (P less than 0.001) in hypocalcemic dogs, +19.1 +/- 4.4% (P less than 0.001) in normolcalcemic dogs, and +15.5 +/- 1.5% (P less than 0.001) in hypercalcemic dogs. We conclude that increases in plasma calcium potentiate the phosphaturic effect of PTH. This potentiating effect is attenuated in marked hypercalcemia by superimposed hemodynamic and/or metabolic changes.", "contents": "Intrarenal calcium in phosphate handling. The intrarenal role of plasma ionized calcium (Ca), on fractional phosphate excretion (FE PO4) was investigated in dogs with control of parathyroid hormone (PTH). In series 1, acute thyroparathyroidectomy was immediately followed by a constant infusion of bovine PTH (0.01 U/kg per min). Subsequent calcium chloride infusions increased Cai in plasma phosphate and decreased in the percentage of ultrafiltrable phosphate. A 20% increase in Cai significantly increased FE PO4 by +3.82 +/- 0.97% (P less than 0.01) when infused intravenously and by +2.62 +/- 1.06% (P less than 0.05) when infused in the renal artery. In contrast, a 75% increase in Cai did not significantly change FE PO4. In series 2, dogs were thyroparathyroidectomized 18 h before experiments, and no PTH infusion was initiated. A bolus of bovine PTH (30 U/kg) increased FE PO4 + 8.9 +/- 0.9% (P less than 0.001) in hypocalcemic dogs, +19.1 +/- 4.4% (P less than 0.001) in normolcalcemic dogs, and +15.5 +/- 1.5% (P less than 0.001) in hypercalcemic dogs. We conclude that increases in plasma calcium potentiate the phosphaturic effect of PTH. This potentiating effect is attenuated in marked hypercalcemia by superimposed hemodynamic and/or metabolic changes."} {"id": "PMID:1266985", "title": "Hypothalamic and brachial nerve effects on circulation of isolated canine forelimb,.", "content": "Canine forelimbs were vascularly isolated and perfused at either constant inflow or constant inflow pressure. A comparison of the effects of electrical stimulation of hypothalamic pressor areas and brachial nerves was made on several vascular parameters. During constant pressure perfusion, forelimb resistance increased and total forelimb volume decreased. Additionally active vascular volumes measured with 131I-labeled albumin and 51Cr-labeled red cells decreased significantly. Capillary diffusion capacity product calculated from extraction of 86RbCl also decreased significantly as did the capillary filtration coefficient (CFC). The only significant differences between hypothalamic and brachial nerve stimulation were noted in the larger decreases in active volumes and CFC during the latter stimulations.", "contents": "Hypothalamic and brachial nerve effects on circulation of isolated canine forelimb,. Canine forelimbs were vascularly isolated and perfused at either constant inflow or constant inflow pressure. A comparison of the effects of electrical stimulation of hypothalamic pressor areas and brachial nerves was made on several vascular parameters. During constant pressure perfusion, forelimb resistance increased and total forelimb volume decreased. Additionally active vascular volumes measured with 131I-labeled albumin and 51Cr-labeled red cells decreased significantly. Capillary diffusion capacity product calculated from extraction of 86RbCl also decreased significantly as did the capillary filtration coefficient (CFC). The only significant differences between hypothalamic and brachial nerve stimulation were noted in the larger decreases in active volumes and CFC during the latter stimulations."} {"id": "PMID:1266986", "title": "Effect of a fixed pyloric opening on gastric emptying in the cat and dog.", "content": "The effect of preventing pyloric closure on the rate of gastric emptying without alteration of the gastroduodenal junction was studied in six dogs and four cats with gastric fistulas. Each had a Teflon cannula with an internal diameter of 1.0 or 1.25 cm (dog) and 0.6 cm (cat) sewn into the pyloric channel. At the completion of the initial series of tests, the cannulas were removed and the studies repeated. Test meals were 240 and 480 ml of water, acid (120 mM HC1), and hyperosmotic glucose (555 mM) in the dogs and 50 ml of water, acid (100 mM HC1) and fat (20 mM Na oleate) in the cats. Phenol red was used as a nonabsorbable marker. The residual volumes were collected at 15-40 min in the dogs and 15-20 min in the cats. In both species, the rate of emptying of all the meals was unaffected by the pyloric cannula. In the dog, added secretions were greater with the pyloric cannula in place, suggesting reflux of duodenal contents. This study indicates that while the pylorus is unimportant in the gastric emptying of liquids in the dog and cat, it may have a role in prevention of duodenal reflux.", "contents": "Effect of a fixed pyloric opening on gastric emptying in the cat and dog. The effect of preventing pyloric closure on the rate of gastric emptying without alteration of the gastroduodenal junction was studied in six dogs and four cats with gastric fistulas. Each had a Teflon cannula with an internal diameter of 1.0 or 1.25 cm (dog) and 0.6 cm (cat) sewn into the pyloric channel. At the completion of the initial series of tests, the cannulas were removed and the studies repeated. Test meals were 240 and 480 ml of water, acid (120 mM HC1), and hyperosmotic glucose (555 mM) in the dogs and 50 ml of water, acid (100 mM HC1) and fat (20 mM Na oleate) in the cats. Phenol red was used as a nonabsorbable marker. The residual volumes were collected at 15-40 min in the dogs and 15-20 min in the cats. In both species, the rate of emptying of all the meals was unaffected by the pyloric cannula. In the dog, added secretions were greater with the pyloric cannula in place, suggesting reflux of duodenal contents. This study indicates that while the pylorus is unimportant in the gastric emptying of liquids in the dog and cat, it may have a role in prevention of duodenal reflux."} {"id": "PMID:1266987", "title": "Effect of hemorrhagic shock on renal release of prostaglandin E.", "content": "The effect of hemorrhage and reinfusion on renal release of prostaglandin E (PGE), arterial [PGE], mixed-venous [PGE], and renal function was observed in anesthetized dogs. Following hemorrhage to 60 mmHg arterial pressure, arterial [PGE] rose significantly from 405 to 740 pg/ml. Renal release of PGE remained near control (8 ng/min), as renal blood flow (RBF) decreased from 4.7 to 2.2 ng/min per gram kidney weight (KW). Mixed-venous [PGE] remained near the control value (960 pg/ml). Reinfusion of shed blood restored RBF to 4.0 ml/min per KW. Renal release of PGE rose significantly to 190 ng/min. Arterial [PGE] remained elevated, but mixed-venous [PGE] was not significantly different from control. Indomethacin, a prostaglandin synthesis inhibitor, caused a significant decrease in renal release of PGE. Arterial [PGE] remained elevated following treatment. The inhibition of PGE release from the kidney by indomethacin indicates that increased renal release of PGE following reinfusion is the result of accelerated PGE synthesis. The data suggest that the elevated arterial [PGE] may be the result of alteration of the handling of PGE by the lung.", "contents": "Effect of hemorrhagic shock on renal release of prostaglandin E. The effect of hemorrhage and reinfusion on renal release of prostaglandin E (PGE), arterial [PGE], mixed-venous [PGE], and renal function was observed in anesthetized dogs. Following hemorrhage to 60 mmHg arterial pressure, arterial [PGE] rose significantly from 405 to 740 pg/ml. Renal release of PGE remained near control (8 ng/min), as renal blood flow (RBF) decreased from 4.7 to 2.2 ng/min per gram kidney weight (KW). Mixed-venous [PGE] remained near the control value (960 pg/ml). Reinfusion of shed blood restored RBF to 4.0 ml/min per KW. Renal release of PGE rose significantly to 190 ng/min. Arterial [PGE] remained elevated, but mixed-venous [PGE] was not significantly different from control. Indomethacin, a prostaglandin synthesis inhibitor, caused a significant decrease in renal release of PGE. Arterial [PGE] remained elevated following treatment. The inhibition of PGE release from the kidney by indomethacin indicates that increased renal release of PGE following reinfusion is the result of accelerated PGE synthesis. The data suggest that the elevated arterial [PGE] may be the result of alteration of the handling of PGE by the lung."} {"id": "PMID:1266988", "title": "Blood flow and relative tissue PO2 of brain and muscle: effect of various gas mixtures.", "content": "The effects of inspiring low O2 or high CO2, or low-O2-high-CO2 gas mixtures on tissue perfusion and tissue Po2 of brain and muscle were studied in 76 anesthetized rats. Under control conditions, relative tissue Po2 of cerebral white matter measured polarographically averaged 16.4 mmHg and 18.7 mmHg in the biceps brachii. With low-O2 gas mixtures, tissue Po2 declined in both brain and muscle, but more in muscle. Tissue Po2 increased under high-CO2 conditions, with the brain increasing to a greater extent. Control cerebral cortex tissue perfusion averaged 23.5 ml/min per 100 g and muscle was 18.3 ml/min per 100 g measured by H2 clearance. Brain perfusion increased under all experimental conditions. Muscle perfusion did not change with low O2 alone, but increased with low-O2-high-CO2 or high-CO2 gas mixtures. Brain perfusion increased under all conditions significantly more than muscle. The brain appeared better protected compared to skeletal muscle in terms of tissue Po2 and perfusion under the stress of hypoxia and hypoxic-hypercapnia. The effects of hypercapnia are also greater on the brain.", "contents": "Blood flow and relative tissue PO2 of brain and muscle: effect of various gas mixtures. The effects of inspiring low O2 or high CO2, or low-O2-high-CO2 gas mixtures on tissue perfusion and tissue Po2 of brain and muscle were studied in 76 anesthetized rats. Under control conditions, relative tissue Po2 of cerebral white matter measured polarographically averaged 16.4 mmHg and 18.7 mmHg in the biceps brachii. With low-O2 gas mixtures, tissue Po2 declined in both brain and muscle, but more in muscle. Tissue Po2 increased under high-CO2 conditions, with the brain increasing to a greater extent. Control cerebral cortex tissue perfusion averaged 23.5 ml/min per 100 g and muscle was 18.3 ml/min per 100 g measured by H2 clearance. Brain perfusion increased under all experimental conditions. Muscle perfusion did not change with low O2 alone, but increased with low-O2-high-CO2 or high-CO2 gas mixtures. Brain perfusion increased under all conditions significantly more than muscle. The brain appeared better protected compared to skeletal muscle in terms of tissue Po2 and perfusion under the stress of hypoxia and hypoxic-hypercapnia. The effects of hypercapnia are also greater on the brain."} {"id": "PMID:1266989", "title": "Effects of saline drinking on malignant course of renal hypertension in rats.", "content": "In rats with unilateral renal artery stenosis and an intact contralateral kidney, a malignant course of hypertension (MH) may develop, which is characterized by 1) high BP levels, 2) sodium and water loss and a polyuric-polydipsic syndrome, 3) marked activation of the renin-angiotensin system, 4) malignant nephrosclerosis in the contralateral kidney and high plasma urea concentrations, and 5) deterioration of the animals' general condition. (Some rats exhibit signs of a cerebral vascular crisis; some rats die). When such rats are offered in addition to water 0.9% NaCl, they compulsively drink the saline, BP falls for some days to levels found in the other hypertensive animals, and signs of MH nearly or completely disappear. It is concluded that high saline intake has, for a limited period, a beneficial effect on the malignant course of renal hypertension in rats. The observations made are consistent with the hypothesis that salt and water loss, which ensue subsequent to an increase of BP into a critical high range might trigger the onset of malignant hypertension.", "contents": "Effects of saline drinking on malignant course of renal hypertension in rats. In rats with unilateral renal artery stenosis and an intact contralateral kidney, a malignant course of hypertension (MH) may develop, which is characterized by 1) high BP levels, 2) sodium and water loss and a polyuric-polydipsic syndrome, 3) marked activation of the renin-angiotensin system, 4) malignant nephrosclerosis in the contralateral kidney and high plasma urea concentrations, and 5) deterioration of the animals' general condition. (Some rats exhibit signs of a cerebral vascular crisis; some rats die). When such rats are offered in addition to water 0.9% NaCl, they compulsively drink the saline, BP falls for some days to levels found in the other hypertensive animals, and signs of MH nearly or completely disappear. It is concluded that high saline intake has, for a limited period, a beneficial effect on the malignant course of renal hypertension in rats. The observations made are consistent with the hypothesis that salt and water loss, which ensue subsequent to an increase of BP into a critical high range might trigger the onset of malignant hypertension."} {"id": "PMID:1266991", "title": "Tachypnea after stimulation of afferent cardiac sympathetic nerve fibers.", "content": "The role of afferent cardiac sympathetic nerve fibers in the regulation of respiration has been examined. Application of potassium chloride or lactic acid solutions to the left ventricular surface of anesthetized vagotomized dogs resulted in a decrease in the manimum firing rate and shortening in period duration of firing of phrenic nerves. Also, application of the agents caused a decrease in amplitude and an increase in rate of respiratory thoracic movements. The same changes in phrenic nerve activity and respiratory movements were produced by coronary artery occlusion and centrifugal electrical stimulation of the left inferior cardiac nerves. The results indicate tachypnea that can be produced by excitation of afferent cardiac sympathetic nerve fibers.", "contents": "Tachypnea after stimulation of afferent cardiac sympathetic nerve fibers. The role of afferent cardiac sympathetic nerve fibers in the regulation of respiration has been examined. Application of potassium chloride or lactic acid solutions to the left ventricular surface of anesthetized vagotomized dogs resulted in a decrease in the manimum firing rate and shortening in period duration of firing of phrenic nerves. Also, application of the agents caused a decrease in amplitude and an increase in rate of respiratory thoracic movements. The same changes in phrenic nerve activity and respiratory movements were produced by coronary artery occlusion and centrifugal electrical stimulation of the left inferior cardiac nerves. The results indicate tachypnea that can be produced by excitation of afferent cardiac sympathetic nerve fibers."} {"id": "PMID:1266992", "title": "Effect of initial length on relations between oxygen uptake and load in dog muscle.", "content": "Oxygen uptake for brief tetanic contractions was calculated from measurements of blood flow and blood arteriovenous oxygen content differences. Each muscle preparation was pretested under isometric conditions to establish optimal length, Lo. After this one group of preparations performed afterload isotonic contractions at several loads with initial length, Li, less than Lo. The other groups of preparations performed similar contractions with Li greater than Lo. When Li was less than Lo, oxygen uptake for the highest load was always greater than oxygen uptake at the lowest load whereas intermediate loads were usually higher than both extremes. However, when Li was greater than Lo, oxygen uptake at the highest load was always less than oxygen uptake at the lowest load; again the intermediate loads were usually higher than both extremes. The data confirm and extend similar effects of initial length on heat production for contractions by amphibian muscles (7). It seems likely that the differences in initial lengths may account for the fact that the Fenn effect has not previously been observed in studies of mammalian skeletal muscle energetics.", "contents": "Effect of initial length on relations between oxygen uptake and load in dog muscle. Oxygen uptake for brief tetanic contractions was calculated from measurements of blood flow and blood arteriovenous oxygen content differences. Each muscle preparation was pretested under isometric conditions to establish optimal length, Lo. After this one group of preparations performed afterload isotonic contractions at several loads with initial length, Li, less than Lo. The other groups of preparations performed similar contractions with Li greater than Lo. When Li was less than Lo, oxygen uptake for the highest load was always greater than oxygen uptake at the lowest load whereas intermediate loads were usually higher than both extremes. However, when Li was greater than Lo, oxygen uptake at the highest load was always less than oxygen uptake at the lowest load; again the intermediate loads were usually higher than both extremes. The data confirm and extend similar effects of initial length on heat production for contractions by amphibian muscles (7). It seems likely that the differences in initial lengths may account for the fact that the Fenn effect has not previously been observed in studies of mammalian skeletal muscle energetics."} {"id": "PMID:1266993", "title": "Oxygen uptake for negative work, stretching contractions by in situ dog skeletal muscle.", "content": "Oxygen uptake for negative work, stretching twitch contractions by in situ gastrocnemius-plantaris muscle was calculated from measurements of venous outflow and arterial and venous blood oxygen contents. Contractions were produced by valving air at high pressure into the pneumatic lever 10-50 ms before stimulation of the muscle. The loads produced were up to about 2.5 times isometric. Muscle length was always below optimal isometric length. Oxygen uptake for shortening contractions increased with increasing load up to isometric load. Oxygen uptake for stretching contractions decreased with increasing loads above isometric load. Velocity of shortening decreased with increasing loads up to isometric load whereas velocity of stretching increased with increasing loads above isometric. In shortening contractions external work done by the muscle was greatest at intermediate loads, but in stretching contractions the work done on the muscle increased with increasing loads. In stretching contractions the ratio of the energy equivalent of the work absorbed by the muscle reached 8.0 times the energy equivalent of the oxygen uptake. Since this ratio cannot exceed 1.0 for an engine, muscles must act as brakes during stretching contractions.", "contents": "Oxygen uptake for negative work, stretching contractions by in situ dog skeletal muscle. Oxygen uptake for negative work, stretching twitch contractions by in situ gastrocnemius-plantaris muscle was calculated from measurements of venous outflow and arterial and venous blood oxygen contents. Contractions were produced by valving air at high pressure into the pneumatic lever 10-50 ms before stimulation of the muscle. The loads produced were up to about 2.5 times isometric. Muscle length was always below optimal isometric length. Oxygen uptake for shortening contractions increased with increasing load up to isometric load. Oxygen uptake for stretching contractions decreased with increasing loads above isometric load. Velocity of shortening decreased with increasing loads up to isometric load whereas velocity of stretching increased with increasing loads above isometric. In shortening contractions external work done by the muscle was greatest at intermediate loads, but in stretching contractions the work done on the muscle increased with increasing loads. In stretching contractions the ratio of the energy equivalent of the work absorbed by the muscle reached 8.0 times the energy equivalent of the oxygen uptake. Since this ratio cannot exceed 1.0 for an engine, muscles must act as brakes during stretching contractions."} {"id": "PMID:1266994", "title": "Inhibition of the CNA trigger process for arousal from hibernation.", "content": "Ground squirrels (Citellus lateralis) produced three distinct types of thermogenic response during hibernation. These responses were evoked spontaneously as well as after stimulation produced by brief handling, or after microinjection of acetylcholine into the midbrain reticular formation. Type I responses were characterized by small magnitude and a slow (mean rate, 0.03 degrees C/min), variable rising phase. Type II responses were characterized by a smooth, rapid rising phase with a mean rate of increase of 0.11 degrees C/min and by an abrupt reversal of the rising phase within a restricted ceiling temperature band with a mean value of 9.4 degrees C. The third type of response, full arousal, was characterized by a return of body temperature to euthermic (nonhibernating) levels and by an early rising phase that was indistinguishable from the rising phase of type II responses. This indicates that the rising phase of type II responses and the duplicate portion of full arousals are produced by a common neuronal mechanism that functions as the trigger for arousal from hibernation, and that this mechanism can be spontaneously inhibited when increasing internal temperature reaches a hibernation ceiling level.", "contents": "Inhibition of the CNA trigger process for arousal from hibernation. Ground squirrels (Citellus lateralis) produced three distinct types of thermogenic response during hibernation. These responses were evoked spontaneously as well as after stimulation produced by brief handling, or after microinjection of acetylcholine into the midbrain reticular formation. Type I responses were characterized by small magnitude and a slow (mean rate, 0.03 degrees C/min), variable rising phase. Type II responses were characterized by a smooth, rapid rising phase with a mean rate of increase of 0.11 degrees C/min and by an abrupt reversal of the rising phase within a restricted ceiling temperature band with a mean value of 9.4 degrees C. The third type of response, full arousal, was characterized by a return of body temperature to euthermic (nonhibernating) levels and by an early rising phase that was indistinguishable from the rising phase of type II responses. This indicates that the rising phase of type II responses and the duplicate portion of full arousals are produced by a common neuronal mechanism that functions as the trigger for arousal from hibernation, and that this mechanism can be spontaneously inhibited when increasing internal temperature reaches a hibernation ceiling level."} {"id": "PMID:1266995", "title": "Effect of cervical sympathetic nerve stimulation on canine carotid sinus reflex.", "content": "In the chloralose-anesthetized dog the carotid sinus on one side of the neck was isolated vascularly. Pressure in the isolated sinus [carotid sinus pressure (CSP)], electrocardiogram, and systemic arterial pressure were recorded. Both vagosympathetic trunks were cut and the contralateral common carotid artery was occluded or the contralateral sinus nerve was cut to reduce reflex buffering of arterial pressure changes. By varying CSP from 50 to 250 mmHg the full range of the reflex response was examined. Electrical stimulation of the peripheral end of the cut ipsilateral cervical sympathetic nerve brought about a rapid decrease in mean arterial pressure (MAP) and heart rate (HR) at lower CSPs, no change in these variables at midrange CSPs, and a gradual increase at higher CSPs, such that the gain of the reflex was reduced (1.89 +/- 0.19 to 1.33 +/- 0.15 mmHg/mmHg). The decrease in MAP and HR at lower CSPs implies an increase in baroreceptor activity whereas the converse would appear to occur at higher CSPs. These responses attained a maximum value at low stimulus frequencies (less than 10 Hz).", "contents": "Effect of cervical sympathetic nerve stimulation on canine carotid sinus reflex. In the chloralose-anesthetized dog the carotid sinus on one side of the neck was isolated vascularly. Pressure in the isolated sinus [carotid sinus pressure (CSP)], electrocardiogram, and systemic arterial pressure were recorded. Both vagosympathetic trunks were cut and the contralateral common carotid artery was occluded or the contralateral sinus nerve was cut to reduce reflex buffering of arterial pressure changes. By varying CSP from 50 to 250 mmHg the full range of the reflex response was examined. Electrical stimulation of the peripheral end of the cut ipsilateral cervical sympathetic nerve brought about a rapid decrease in mean arterial pressure (MAP) and heart rate (HR) at lower CSPs, no change in these variables at midrange CSPs, and a gradual increase at higher CSPs, such that the gain of the reflex was reduced (1.89 +/- 0.19 to 1.33 +/- 0.15 mmHg/mmHg). The decrease in MAP and HR at lower CSPs implies an increase in baroreceptor activity whereas the converse would appear to occur at higher CSPs. These responses attained a maximum value at low stimulus frequencies (less than 10 Hz)."} {"id": "PMID:1266996", "title": "Ba2+ and K+ alteration of K+ conductance in spontaneously active vascular muscle.", "content": "The spontaneous spiking of vascular muscle in hepatic portal vein was converted from a burst pattern to single spiking by K+ concentrations greater than 20 mM. A pronounced decrease in contraction amplitude was always associated with the conversion of bursts of spikes to single spikes. The single spikes were accompanied by contractions that were only 1-5% of the magnitude of the contractions associated with spike bursts. Ba2+ (1 mM) increased the number of spikes per burst in myovascular cells at low(less than 10 mM) K+ concentrations. Even though Ba2+ caused depolarization, which itself tended to cause conversion to single spiking, the number of spikes per burst and contraction amplitude were greater in Ba2+ solutions. The slope of the Em-log [K+]o relationship depended on the time allowed for changes in [K+], and a maximum slope of 36 mV/decade and an extrapolated [K+]i of 160 mM were the highest slope and lowest [K+]i values recorded. Ba2+ slightly decreased (to 28 mV/decade) the slope of the curve but did not alter the intercept at [K+] = 160 mM. Ba2+ caused an increase in input resistance (rin) and depolarization independent of CL- concentration, and thus appeared to decrease K+ conductance. K+ concentration increases tended to increase K+ conductance (decrease rin) with depolarization. Spontaneously active vascular muscle thus appears to have a K+ conductance that can be altered and to show different spike patterns and altered conduction, resulting in a marked change in contractions. The spike pattern appears to depend at least partially on the combination of K+ conductance and Em.", "contents": "Ba2+ and K+ alteration of K+ conductance in spontaneously active vascular muscle. The spontaneous spiking of vascular muscle in hepatic portal vein was converted from a burst pattern to single spiking by K+ concentrations greater than 20 mM. A pronounced decrease in contraction amplitude was always associated with the conversion of bursts of spikes to single spikes. The single spikes were accompanied by contractions that were only 1-5% of the magnitude of the contractions associated with spike bursts. Ba2+ (1 mM) increased the number of spikes per burst in myovascular cells at low(less than 10 mM) K+ concentrations. Even though Ba2+ caused depolarization, which itself tended to cause conversion to single spiking, the number of spikes per burst and contraction amplitude were greater in Ba2+ solutions. The slope of the Em-log [K+]o relationship depended on the time allowed for changes in [K+], and a maximum slope of 36 mV/decade and an extrapolated [K+]i of 160 mM were the highest slope and lowest [K+]i values recorded. Ba2+ slightly decreased (to 28 mV/decade) the slope of the curve but did not alter the intercept at [K+] = 160 mM. Ba2+ caused an increase in input resistance (rin) and depolarization independent of CL- concentration, and thus appeared to decrease K+ conductance. K+ concentration increases tended to increase K+ conductance (decrease rin) with depolarization. Spontaneously active vascular muscle thus appears to have a K+ conductance that can be altered and to show different spike patterns and altered conduction, resulting in a marked change in contractions. The spike pattern appears to depend at least partially on the combination of K+ conductance and Em."} {"id": "PMID:1266997", "title": "Hemodynamic mechanisms influencing sodium excretion during angiotensin infusion.", "content": "To examine mechanisms of transition between antinatriuresis and natriuresis, angiotensin II was first infused intrarenally (0.001-0.07 mug/kg-min) in anesthetized dogs; glomerular filtration rate (GFR), sodium excretion, and intrarenal pressure (IRP), indicating tubular pressure, fell as during mechanical aortic constriction. During supplementary intravenous infusion (0.10-0.30 mug/kg-min), renal blood flow (RBF) rose toward control (tachyphylaxis). Tubular reabsorption increased but was still 17.1% below control. Filtration fraction averaging 0.31 remained constant. Sodium excretion and IRP exceeded control but were normalized by restoring renal arterial pressure mechanically. During intrarenal angiotensin infusion, carotid constriction increased blood pressure more, but RBF, IRP, and sodium excretion less than intravenous angiotensin. Intrarenal infusion of angiotensin at 0.10-0.20 mug/kg-min increased RBF and sodium excretion more in infused than in contralateral kidneys. Thus, angiotensin natriuresis depends on increased perfusion pressure and is augmented as tachyphylaxis develops. High correlation between sodium excretion and IRP at unchanged filtration fraction suggests a regulation of sodium excretion by hydrostatic rather than oncotic pressures in glomerular and peritubular capillaries.", "contents": "Hemodynamic mechanisms influencing sodium excretion during angiotensin infusion. To examine mechanisms of transition between antinatriuresis and natriuresis, angiotensin II was first infused intrarenally (0.001-0.07 mug/kg-min) in anesthetized dogs; glomerular filtration rate (GFR), sodium excretion, and intrarenal pressure (IRP), indicating tubular pressure, fell as during mechanical aortic constriction. During supplementary intravenous infusion (0.10-0.30 mug/kg-min), renal blood flow (RBF) rose toward control (tachyphylaxis). Tubular reabsorption increased but was still 17.1% below control. Filtration fraction averaging 0.31 remained constant. Sodium excretion and IRP exceeded control but were normalized by restoring renal arterial pressure mechanically. During intrarenal angiotensin infusion, carotid constriction increased blood pressure more, but RBF, IRP, and sodium excretion less than intravenous angiotensin. Intrarenal infusion of angiotensin at 0.10-0.20 mug/kg-min increased RBF and sodium excretion more in infused than in contralateral kidneys. Thus, angiotensin natriuresis depends on increased perfusion pressure and is augmented as tachyphylaxis develops. High correlation between sodium excretion and IRP at unchanged filtration fraction suggests a regulation of sodium excretion by hydrostatic rather than oncotic pressures in glomerular and peritubular capillaries."} {"id": "PMID:1266998", "title": "Regulatory and secondary water intake in rats with lesions of the zona incerta.", "content": "Bilateral electrolytic lesions of the zona incerta (ZI) permanently reduced daily water intake of rats by 20-30%. Lesioned rats did not differ from controls in daily food intake, body weight, hematocrit, or serum osmolality, Na+ or K+ levels. The hypodipsia was not caused by changes in water requirements or excretory function or by a nonspecific depression of behavior. Compensatory reductions in water losses maintained fluid balance. Lesioned rats drank as much water as controls in response to intracellular and extracellular dehydration, but unlike controls, appeared to restrict their daily water intake to these regulatory responses. Lesions of the ZI attenuated the ingestion of extra water observed when rats were maintained on a liquid diet adequate to meet fluid requirements, and daily water intake of lesioned but not control rats closely followed changes in water needs. It was concluded that lesions of the ZI reduce daily water intake towards minimal requirements for fluid balance by attenuating secondary drinking (drinking independent of water needs for fluid homeostasis.", "contents": "Regulatory and secondary water intake in rats with lesions of the zona incerta. Bilateral electrolytic lesions of the zona incerta (ZI) permanently reduced daily water intake of rats by 20-30%. Lesioned rats did not differ from controls in daily food intake, body weight, hematocrit, or serum osmolality, Na+ or K+ levels. The hypodipsia was not caused by changes in water requirements or excretory function or by a nonspecific depression of behavior. Compensatory reductions in water losses maintained fluid balance. Lesioned rats drank as much water as controls in response to intracellular and extracellular dehydration, but unlike controls, appeared to restrict their daily water intake to these regulatory responses. Lesions of the ZI attenuated the ingestion of extra water observed when rats were maintained on a liquid diet adequate to meet fluid requirements, and daily water intake of lesioned but not control rats closely followed changes in water needs. It was concluded that lesions of the ZI reduce daily water intake towards minimal requirements for fluid balance by attenuating secondary drinking (drinking independent of water needs for fluid homeostasis."} {"id": "PMID:1266999", "title": "Elastic behavior of brain tissue in vivo.", "content": "A measurement system and a test sequence have been developed to determine the in vivo elastic response of brain tissue in terms of a pressure-depth ratio. This parameter appears sensitive to changes in the tissue environment that may occur due to the influence of, e.g., anesthetic agents, hyperventilation, etc., and thus may be useful in evaluating such influences. The measurements are made with the dura-arachnoid membranes intact, thus maintaining the influence of the cerebrospinal fluid compartment on the response behavior of the brain tissue that comprises the subpial region. As an integral part of the test, the procedure also serves to determine the depth or position of the subpial region and thus assures that the subsequent pressure-depth measurements invole brain tissue response. Finally, some discussion is given to relating the measured pressure-depth ratio to the classical elastic modulus. Values of the pressure-depth ratio and the corresponding elastic modulus for seven dogs are given.", "contents": "Elastic behavior of brain tissue in vivo. A measurement system and a test sequence have been developed to determine the in vivo elastic response of brain tissue in terms of a pressure-depth ratio. This parameter appears sensitive to changes in the tissue environment that may occur due to the influence of, e.g., anesthetic agents, hyperventilation, etc., and thus may be useful in evaluating such influences. The measurements are made with the dura-arachnoid membranes intact, thus maintaining the influence of the cerebrospinal fluid compartment on the response behavior of the brain tissue that comprises the subpial region. As an integral part of the test, the procedure also serves to determine the depth or position of the subpial region and thus assures that the subsequent pressure-depth measurements invole brain tissue response. Finally, some discussion is given to relating the measured pressure-depth ratio to the classical elastic modulus. Values of the pressure-depth ratio and the corresponding elastic modulus for seven dogs are given."} {"id": "PMID:1267000", "title": "Effect of prolonged angiotensin II infusion on thirst.", "content": "To determine the effect of prolonged angiotensin II (A-II) infusion on thirst, daily water intake by drinking was measured in dogs during a 4-day control period, a 4-day period of vehicle infusion without A-II, a 10-day period of A-II infusion, and a 4-day recovery period of vehicle infusion without A-II. During the control period and the periods of vehicle infusion in the absence of A-II, daily water intake by drinking in four dogs averaged 118 +/- 20 ml/day (mean +/- SE). During the 10-day period of A-II infusion at the rate of 13.0 ng/kg per min drinking increased to 269 +/- 49 ml/day (paired t; P less than 0.05). Angiotensin II infusion at the rate of 26.0 ng/kg per min produced a sustained increase in water intake in two dogs during an 8-day period of infusion. These results demonstrate that in dogs, prolonged infusion of angiotensin II stimulates the thirst mechanism and that the effect lasts for more than a few days.", "contents": "Effect of prolonged angiotensin II infusion on thirst. To determine the effect of prolonged angiotensin II (A-II) infusion on thirst, daily water intake by drinking was measured in dogs during a 4-day control period, a 4-day period of vehicle infusion without A-II, a 10-day period of A-II infusion, and a 4-day recovery period of vehicle infusion without A-II. During the control period and the periods of vehicle infusion in the absence of A-II, daily water intake by drinking in four dogs averaged 118 +/- 20 ml/day (mean +/- SE). During the 10-day period of A-II infusion at the rate of 13.0 ng/kg per min drinking increased to 269 +/- 49 ml/day (paired t; P less than 0.05). Angiotensin II infusion at the rate of 26.0 ng/kg per min produced a sustained increase in water intake in two dogs during an 8-day period of infusion. These results demonstrate that in dogs, prolonged infusion of angiotensin II stimulates the thirst mechanism and that the effect lasts for more than a few days."} {"id": "PMID:1267001", "title": "Independence of onset of compensatory kidney growth from changes in renal function.", "content": "Renal function was measure before and shortly after uninephrectomy in mice to evaluate if work expended in the reabsorption of glomerular filtrate plays a role in the initiation of compensatory growth. To exclude the possibility of small but undetectable increments in glomerular filtration rate and absolute sodium reabsorption these functions were experimentally reduced immediately after uninephrectomy and sham nephrectomy. The onset of growth was indicated by an increased rate of [14C]choline incorporation into phospholipid in renal cortical slices. [14C]choline incorporation increased significantly only after uninephrectomy and remained unchanged after sham operation regardless of the magnitude or direction of the concurrent change in sodium reabsorption. The rate of incorporation increased by 40 +/- 8% (P less than 0.005) in uninephrectomized animals whose sodium reabsorption was reduced by 34 +/- 6% (P less than 0.001) and rose 45 +/- 11% (P less than 0.005) when sodium reabsorption remained unchanged. These results indicate that compensatory kidney growth is not triggered by an increase in renal work expended in the reabsorption of glomerular filtrate; in fact, it can occur when reabsorptive work is substantially decreased.", "contents": "Independence of onset of compensatory kidney growth from changes in renal function. Renal function was measure before and shortly after uninephrectomy in mice to evaluate if work expended in the reabsorption of glomerular filtrate plays a role in the initiation of compensatory growth. To exclude the possibility of small but undetectable increments in glomerular filtration rate and absolute sodium reabsorption these functions were experimentally reduced immediately after uninephrectomy and sham nephrectomy. The onset of growth was indicated by an increased rate of [14C]choline incorporation into phospholipid in renal cortical slices. [14C]choline incorporation increased significantly only after uninephrectomy and remained unchanged after sham operation regardless of the magnitude or direction of the concurrent change in sodium reabsorption. The rate of incorporation increased by 40 +/- 8% (P less than 0.005) in uninephrectomized animals whose sodium reabsorption was reduced by 34 +/- 6% (P less than 0.001) and rose 45 +/- 11% (P less than 0.005) when sodium reabsorption remained unchanged. These results indicate that compensatory kidney growth is not triggered by an increase in renal work expended in the reabsorption of glomerular filtrate; in fact, it can occur when reabsorptive work is substantially decreased."} {"id": "PMID:1267002", "title": "Effect of tachycardia on left ventricular blood flow distribution during coronary occlusion.", "content": "The effect of heart rate on the amount and distribution of collateral blood flow was determine in open-chested dogs 1 h after coronary artery ligation. Flows to ischemic and nonischemic regions of left ventricle were measured with 7- to 10- mum diam radioactive microspheres during base-line conditions (118 +/- 6 beats/min) and again during atrial pacing at rates 20 and 40% above control (141 +/- 7 and 165 +/- 9 beats/min). During pacing aortic and left atrial pressures and cardiac output did not change significantly, whereas ST segment elevation in epicardial electrograms increased markedly. In nonischemic myocardium, mean flow increased approximately in proportion to the increase in rate, but subepicardial (EPI) flow increased somewhat more than subendocardial (ENDO) flow. In ischemic myocardium, overall flow did not change significantly, but a redistribution from ENDO to EPO was seen. At the faster rate ENDO flow fell 25% (P less than 0.02), EPI flow increased slightly, and ENDO/EPI fell in 8/9 animals (mean 0.54-0.43, P less than 0.01). The ENDO/EPI maldistribution present in ischemic muscle is thus accentuated by tachycardia; this may account for part of the harmful effect of tachycardia in acute myocardial infarction and may help explain the disproportionate ENDO ischemia seen in angina pectoris.", "contents": "Effect of tachycardia on left ventricular blood flow distribution during coronary occlusion. The effect of heart rate on the amount and distribution of collateral blood flow was determine in open-chested dogs 1 h after coronary artery ligation. Flows to ischemic and nonischemic regions of left ventricle were measured with 7- to 10- mum diam radioactive microspheres during base-line conditions (118 +/- 6 beats/min) and again during atrial pacing at rates 20 and 40% above control (141 +/- 7 and 165 +/- 9 beats/min). During pacing aortic and left atrial pressures and cardiac output did not change significantly, whereas ST segment elevation in epicardial electrograms increased markedly. In nonischemic myocardium, mean flow increased approximately in proportion to the increase in rate, but subepicardial (EPI) flow increased somewhat more than subendocardial (ENDO) flow. In ischemic myocardium, overall flow did not change significantly, but a redistribution from ENDO to EPO was seen. At the faster rate ENDO flow fell 25% (P less than 0.02), EPI flow increased slightly, and ENDO/EPI fell in 8/9 animals (mean 0.54-0.43, P less than 0.01). The ENDO/EPI maldistribution present in ischemic muscle is thus accentuated by tachycardia; this may account for part of the harmful effect of tachycardia in acute myocardial infarction and may help explain the disproportionate ENDO ischemia seen in angina pectoris."} {"id": "PMID:1267003", "title": "Effect of an angiotensin II antagonist on autoregulation in the isolated dog kidney.", "content": "The effect of the specific angiotensin II antagonist (AIIA), [1-sarcosine-8-alanine]angiotensin II, on autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF) in an isolated dog kidney was examined. Infusing the AIIA into the renal artery at 1.9 mug/min inhibited the renal vasoconstrictor action of angiotension II infused simultaneously at 1.15 mug/min. Under conditions of constant renal arterial pressure the AIIA had no significant effect on sodium excretion, GFR, RBF, cortical blood flow distribution (microsphere method), or renin secretion in non-renin-depleted kidneys. Similarly, no agonist properties were observed when the AIIA was infused into renin-depleted kidneys. This dose of the AIIA did not impair the capacity of the isolated kidney to regulate GFR or RBF when renal arterial pressure was increased from 100 to 150 mmHg. Efficiency of autoregulation of GFR and RBF was 77 and 82% of that predicted for perfect autoregulation. These values are not significantly different from those of the isolated kidney not infused with the antagonist. It is concluded that the angiotensin II antagonist, [1-sarcosine-8-alanine]angiotensin II, has no significant agonist properties, that it antagonizes the renal vascular effects of exogenously administered angiotensin II, but does not impair renal autoregulation. These data provide no support for the hypothesis that the renin-angiotensin system mediates the autoregulation of GFR and RBF.", "contents": "Effect of an angiotensin II antagonist on autoregulation in the isolated dog kidney. The effect of the specific angiotensin II antagonist (AIIA), [1-sarcosine-8-alanine]angiotensin II, on autoregulation of glomerular filtration rate (GFR) and renal blood flow (RBF) in an isolated dog kidney was examined. Infusing the AIIA into the renal artery at 1.9 mug/min inhibited the renal vasoconstrictor action of angiotension II infused simultaneously at 1.15 mug/min. Under conditions of constant renal arterial pressure the AIIA had no significant effect on sodium excretion, GFR, RBF, cortical blood flow distribution (microsphere method), or renin secretion in non-renin-depleted kidneys. Similarly, no agonist properties were observed when the AIIA was infused into renin-depleted kidneys. This dose of the AIIA did not impair the capacity of the isolated kidney to regulate GFR or RBF when renal arterial pressure was increased from 100 to 150 mmHg. Efficiency of autoregulation of GFR and RBF was 77 and 82% of that predicted for perfect autoregulation. These values are not significantly different from those of the isolated kidney not infused with the antagonist. It is concluded that the angiotensin II antagonist, [1-sarcosine-8-alanine]angiotensin II, has no significant agonist properties, that it antagonizes the renal vascular effects of exogenously administered angiotensin II, but does not impair renal autoregulation. These data provide no support for the hypothesis that the renin-angiotensin system mediates the autoregulation of GFR and RBF."} {"id": "PMID:1267004", "title": "Direct neural inhibition of insulin secretion in response to systemic hypoglycemia.", "content": "The innervated pancreas of an anesthetized small \"pancreas\" dog was cross-perfused with blood from a large \"support\" dog in order to separate neural from blood-borne influences on the immunoreactive insulin secretion rate (ISR). The arterial plasma reducing sugar (sugar) concentration could be varied independently in the pancreas dog systemic circulation and in its pancreas. After tying of the hepatic arteries and portal vein in the pancreas dog, its systemic arterial plasma sugar concentration was allowed to fall in 10 experiments. This was prevented in five control experiments by intravenous glucose infusion (7 mg/kg-min). In all experiments, pancreatic arterial plasma sugar concentration was sustained, and at 40 min it was elevated 50 mg/100 ml by glucose infusion into the pancreatic blood supply. Bilateral splanchnic nerve section at 120 min caused an increase of the ISR in all experiments, but a greater rise occurred from the pancreases of the 10 dogs allowed to become hypoglycemic (P less than .02). In two further experiments, the splanchnic nerves were not cut, and no rise in ISR occurred. In conclusion, systemic hypoglycemia can inhibit insulin secretion by means of the splanchnic nerves.", "contents": "Direct neural inhibition of insulin secretion in response to systemic hypoglycemia. The innervated pancreas of an anesthetized small \"pancreas\" dog was cross-perfused with blood from a large \"support\" dog in order to separate neural from blood-borne influences on the immunoreactive insulin secretion rate (ISR). The arterial plasma reducing sugar (sugar) concentration could be varied independently in the pancreas dog systemic circulation and in its pancreas. After tying of the hepatic arteries and portal vein in the pancreas dog, its systemic arterial plasma sugar concentration was allowed to fall in 10 experiments. This was prevented in five control experiments by intravenous glucose infusion (7 mg/kg-min). In all experiments, pancreatic arterial plasma sugar concentration was sustained, and at 40 min it was elevated 50 mg/100 ml by glucose infusion into the pancreatic blood supply. Bilateral splanchnic nerve section at 120 min caused an increase of the ISR in all experiments, but a greater rise occurred from the pancreases of the 10 dogs allowed to become hypoglycemic (P less than .02). In two further experiments, the splanchnic nerves were not cut, and no rise in ISR occurred. In conclusion, systemic hypoglycemia can inhibit insulin secretion by means of the splanchnic nerves."} {"id": "PMID:1267005", "title": "Cardiovascular and electrophysiological responses to sympathetic pathway stimulation.", "content": "Anesthetized, vagotomized, and paralyzed cats were used to study the relationship between changes in blood pressure and T2 preganglionic nerve activity elicited by stimulation of descending spinal sympathoexcitatory pathways. While low-frequency stimulation (1-10 Hz) resulted in a depressor response, an attenuation of sympathetic nerve evoked discharges was noted after the second pulse of twin-pulse stimulations with 1,000- to 100-ms intervals between stimuli (corresponding to 1-10 Hz). High-frequency stimulation (greater than 10 Hz) resulted in a pressor response, while preganglionic nerve-evoked discharges were enhanced during twin-pulse stimulations with intervals between stimuli less than 50 ms (corresponding to greater than 20 Hz). These data suggest that the depressor response during low-frequency stimulation may be explained by impulses occurring during the silent period of the previous response. During this time the preganglionic neuron is inexcitable and spontaneous activity is abolished; therefore, the blood pressure falls. High-frequency stimulation may result in a pressor response by increasing the number of preganglionic neurons that are activated. This may be due to a process of temporal summation, with initial stimuli bringing cells closer to their threshold for firing and additional stimuli close in time causing these neurons to discharge.", "contents": "Cardiovascular and electrophysiological responses to sympathetic pathway stimulation. Anesthetized, vagotomized, and paralyzed cats were used to study the relationship between changes in blood pressure and T2 preganglionic nerve activity elicited by stimulation of descending spinal sympathoexcitatory pathways. While low-frequency stimulation (1-10 Hz) resulted in a depressor response, an attenuation of sympathetic nerve evoked discharges was noted after the second pulse of twin-pulse stimulations with 1,000- to 100-ms intervals between stimuli (corresponding to 1-10 Hz). High-frequency stimulation (greater than 10 Hz) resulted in a pressor response, while preganglionic nerve-evoked discharges were enhanced during twin-pulse stimulations with intervals between stimuli less than 50 ms (corresponding to greater than 20 Hz). These data suggest that the depressor response during low-frequency stimulation may be explained by impulses occurring during the silent period of the previous response. During this time the preganglionic neuron is inexcitable and spontaneous activity is abolished; therefore, the blood pressure falls. High-frequency stimulation may result in a pressor response by increasing the number of preganglionic neurons that are activated. This may be due to a process of temporal summation, with initial stimuli bringing cells closer to their threshold for firing and additional stimuli close in time causing these neurons to discharge."} {"id": "PMID:1267006", "title": "Thiamine transport in the central nervous system.", "content": "Total thiamine (free thiamine and thiamine phosphates) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the CSF was measured in rabbits. In vivo, total thiamine transport into CSF, choroid plexus, and brain was saturable. At the normal plasma total thiamine concentration, less than 5% of total thiamine entry into CSF, choroid plexus, and brain was by simple diffusion. The relative turnovers of total thiamine in choroid plexus, whole brain, and CSF were 5, 2, and 14% per h, respectively, when measured by the penetration of 35S-labeled thiamine injected into blood. From the CSF, clearance of [35S]thiamine relative to mannitol was not saturable after the intraventricular injection of various concentrations of thiamine. However, a portion of the [35S]thiamine cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [35S]thiamine against a concentration gradient by an active saturable process that did not depend on pyrophosphorylation of the [35S]thiamine. The [35S]thiamine accumulated within the choroid plexus in vitro was readily released. These results were interpreted as showing that the entry of total thiamine into the brain and CSF from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.", "contents": "Thiamine transport in the central nervous system. Total thiamine (free thiamine and thiamine phosphates) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the CSF was measured in rabbits. In vivo, total thiamine transport into CSF, choroid plexus, and brain was saturable. At the normal plasma total thiamine concentration, less than 5% of total thiamine entry into CSF, choroid plexus, and brain was by simple diffusion. The relative turnovers of total thiamine in choroid plexus, whole brain, and CSF were 5, 2, and 14% per h, respectively, when measured by the penetration of 35S-labeled thiamine injected into blood. From the CSF, clearance of [35S]thiamine relative to mannitol was not saturable after the intraventricular injection of various concentrations of thiamine. However, a portion of the [35S]thiamine cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [35S]thiamine against a concentration gradient by an active saturable process that did not depend on pyrophosphorylation of the [35S]thiamine. The [35S]thiamine accumulated within the choroid plexus in vitro was readily released. These results were interpreted as showing that the entry of total thiamine into the brain and CSF from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus."} {"id": "PMID:1267007", "title": "Protein synthesis and RNA in tissues of the pig.", "content": "The rate of protein synthesis in 75-kg pigs was measured by continuous intravenous infusion of [14C]tyrosine. In the whole body, over 600 g of protein were synthesized each day. In pigs, rats, and man the rate of protein synthesis in the whole body was related to metabolic rate. The fractional rate of synthesis of protein in the tissues was also measured. The proteins of visceral organs (liver kidney, lung, and spleen) were renewed at rates close to 20% per day, those of brain at 8% per day, heart 7% per day, and skeletal muscle 4% per day. A significant correlation was observed between the fractional rate of protein synthesis in the tissue and RNA concentration. Calculation of the total amount of protein synthesized in skeletal muscle of the pig (fractional rate of synthesis X protein content) shows that muscle contributes 42% of whole-body synthesis. By contrast, in the rat only 19% of whole-body synthesis occurs in muscle.", "contents": "Protein synthesis and RNA in tissues of the pig. The rate of protein synthesis in 75-kg pigs was measured by continuous intravenous infusion of [14C]tyrosine. In the whole body, over 600 g of protein were synthesized each day. In pigs, rats, and man the rate of protein synthesis in the whole body was related to metabolic rate. The fractional rate of synthesis of protein in the tissues was also measured. The proteins of visceral organs (liver kidney, lung, and spleen) were renewed at rates close to 20% per day, those of brain at 8% per day, heart 7% per day, and skeletal muscle 4% per day. A significant correlation was observed between the fractional rate of protein synthesis in the tissue and RNA concentration. Calculation of the total amount of protein synthesized in skeletal muscle of the pig (fractional rate of synthesis X protein content) shows that muscle contributes 42% of whole-body synthesis. By contrast, in the rat only 19% of whole-body synthesis occurs in muscle."} {"id": "PMID:1267008", "title": "Ligandin and Z protein in binding of thyroid hormones by the liver.", "content": "Sephadex G-100 chromatography of rat liver supernatant after addition of [125I]T3 revealed four peaks of protein-bound radioactivity in the void volume, albumin, ligandin, and Z-containing regions, respectively. The peaks were identified by cochromatography of BSP and [125I]T3 and immonodiffusion with antiratligandin IgG and antirat Z IgG. Binding of [125I]T4 to rat liver supernatant occurred in void volume, albumin, and Z regions only. Studies in vivo reveal a pattern of [125I]T3 binding to rat liver supernatant fractions quantitatively different from that observed in vitro. [125I]T4 binding to liver supernatant fractions in vivo occurred in all four peaks. BSP or bilirubin added to liver supernatant decreased T3 and T4 binding by each fraction. Flavaspidic acid inhibited binding of T3 and T4 to albumin, ligandin, and Z protein. Phenobarbital pretreatment of rats increased binding of T3 by ligandin and of T4 by albumin-containing fractions. Circular dichroism studies with purified rat liver ligandin suggest that T3 and T4 bind competitively to the same site as does bilirubin; the association constants of T3 and T4 for ligandin are 10(6) and 10(5) M-1, respectively. T4 was bound only by purified ligandin and not by ligandin in liver supernatant. To determine whether unconjugated bilirubin interferes with hepatic uptake of T3, [125I]T3 was administered to icteric homozygous and phenotypically normal heterozygous Gunn rats. Hepatic uptake and supernatant binding [125I]T3 were significantly reduced in homozygous Gunn rats. Hepatic uptake of [125I]T3 was also reduced in vivo by infusion of BSP with or without flavaspidic acid. BSP infusion abolished [125I]T3 binding to ligandin; BSP and flavaspidic acid abolished binding to ligandin and Z. These observations suggest that ligandin and Z protein are thyroid hormone binding proteins in rat liver cytosol and may influence the net flux of iodothyronies from plasma into the liver.", "contents": "Ligandin and Z protein in binding of thyroid hormones by the liver. Sephadex G-100 chromatography of rat liver supernatant after addition of [125I]T3 revealed four peaks of protein-bound radioactivity in the void volume, albumin, ligandin, and Z-containing regions, respectively. The peaks were identified by cochromatography of BSP and [125I]T3 and immonodiffusion with antiratligandin IgG and antirat Z IgG. Binding of [125I]T4 to rat liver supernatant occurred in void volume, albumin, and Z regions only. Studies in vivo reveal a pattern of [125I]T3 binding to rat liver supernatant fractions quantitatively different from that observed in vitro. [125I]T4 binding to liver supernatant fractions in vivo occurred in all four peaks. BSP or bilirubin added to liver supernatant decreased T3 and T4 binding by each fraction. Flavaspidic acid inhibited binding of T3 and T4 to albumin, ligandin, and Z protein. Phenobarbital pretreatment of rats increased binding of T3 by ligandin and of T4 by albumin-containing fractions. Circular dichroism studies with purified rat liver ligandin suggest that T3 and T4 bind competitively to the same site as does bilirubin; the association constants of T3 and T4 for ligandin are 10(6) and 10(5) M-1, respectively. T4 was bound only by purified ligandin and not by ligandin in liver supernatant. To determine whether unconjugated bilirubin interferes with hepatic uptake of T3, [125I]T3 was administered to icteric homozygous and phenotypically normal heterozygous Gunn rats. Hepatic uptake and supernatant binding [125I]T3 were significantly reduced in homozygous Gunn rats. Hepatic uptake of [125I]T3 was also reduced in vivo by infusion of BSP with or without flavaspidic acid. BSP infusion abolished [125I]T3 binding to ligandin; BSP and flavaspidic acid abolished binding to ligandin and Z. These observations suggest that ligandin and Z protein are thyroid hormone binding proteins in rat liver cytosol and may influence the net flux of iodothyronies from plasma into the liver."} {"id": "PMID:1267009", "title": "Dopamine-induced dissociation between renal metabolic rate and sodium reabsorption.", "content": "The stimulatory effect of dopamine on renal energy metabolism and its relationship to changes in tubular sodium reabsorption and plasma concentration of free fatty acids (FFA) were examined in anesthetized dogs. Dopamine infused intravenously at 25 mug/kg body wt-min for 30-60 min increased renal oxygen consumption (Rvo2) by 28 +/- 3%; glomerular filtration rate rose from 37 +/- 3 to 40 +/- 2 ml/min without significant changes in sodium excretion. Plasma FFA increased about 6 times. Total-body metabolic rate increased to 152 +/- 7% and fell to 119 +/- 5% of control after normalizing plasma FFA by beta-pyridylcarbinol; Rvo2 remained unchanged. Cortical and outer medullary heat accumulation rated increased to 137 +/- 6 and 133 +/- 10% after 1 h and to 163 +/- 18 and 179 +/- 26% of control after 2 h of dopamine infusion without further changes in sodium reabsorption. Furosemide reduced cortical and outer medullary metabolic rates as much as in control experiments (14 +/- 8 and 69 +/- 7%, respectively). Hence, dopamine exerts a renal calorigenic effect which cannot be accounted for by increased sodium reabsorption or attributed to increased supply of FFA.", "contents": "Dopamine-induced dissociation between renal metabolic rate and sodium reabsorption. The stimulatory effect of dopamine on renal energy metabolism and its relationship to changes in tubular sodium reabsorption and plasma concentration of free fatty acids (FFA) were examined in anesthetized dogs. Dopamine infused intravenously at 25 mug/kg body wt-min for 30-60 min increased renal oxygen consumption (Rvo2) by 28 +/- 3%; glomerular filtration rate rose from 37 +/- 3 to 40 +/- 2 ml/min without significant changes in sodium excretion. Plasma FFA increased about 6 times. Total-body metabolic rate increased to 152 +/- 7% and fell to 119 +/- 5% of control after normalizing plasma FFA by beta-pyridylcarbinol; Rvo2 remained unchanged. Cortical and outer medullary heat accumulation rated increased to 137 +/- 6 and 133 +/- 10% after 1 h and to 163 +/- 18 and 179 +/- 26% of control after 2 h of dopamine infusion without further changes in sodium reabsorption. Furosemide reduced cortical and outer medullary metabolic rates as much as in control experiments (14 +/- 8 and 69 +/- 7%, respectively). Hence, dopamine exerts a renal calorigenic effect which cannot be accounted for by increased sodium reabsorption or attributed to increased supply of FFA."} {"id": "PMID:1267010", "title": "Effect of lithium of responsiveness of rat uterine smooth muscle to angiotensin.", "content": "Studies were carried out to investigate the effect of Na+ deprivation on the response of rat uterine smooth muscle to angiotensin II (AII). Replacement of Na+ with Li+ in a low-Ca2+-, Mg2+-free solution resulted in a concentration-dependent inhibition of both AII and acetylcholine (ACh)-induced contractions. Inhibition was noted at 10% Li+ substitution and was usually complete when 50% of the Na+ was replaced by Li+. The inhibition was not observed when an equivalent amount of tris(hyroxymethyl)aminomethand (Tris+) or sucrose was used to replace Na+. However, elevation of Ca2+ concentration from 0.2 to 0.5 mM did prevent full expression of the Li+ inhibition of AII. The Li+ effect was rapid in onset (60% inhibition after 5 min preincubation) and readily reversible following removal of the Li+. If, however, the tissue was placed in a depolarizing solution (151 mM KCL), Li+ inhibition of AII WAS NO LONGER OBSERVED. These results are interpreted to mean that Li+ interferes with an essential Ca2+-dependent step involved in membrane excitation following agonist-receptor interaction. The results are discussed in relation to a previously suggested model for AII-induced contractions in this tissue.", "contents": "Effect of lithium of responsiveness of rat uterine smooth muscle to angiotensin. Studies were carried out to investigate the effect of Na+ deprivation on the response of rat uterine smooth muscle to angiotensin II (AII). Replacement of Na+ with Li+ in a low-Ca2+-, Mg2+-free solution resulted in a concentration-dependent inhibition of both AII and acetylcholine (ACh)-induced contractions. Inhibition was noted at 10% Li+ substitution and was usually complete when 50% of the Na+ was replaced by Li+. The inhibition was not observed when an equivalent amount of tris(hyroxymethyl)aminomethand (Tris+) or sucrose was used to replace Na+. However, elevation of Ca2+ concentration from 0.2 to 0.5 mM did prevent full expression of the Li+ inhibition of AII. The Li+ effect was rapid in onset (60% inhibition after 5 min preincubation) and readily reversible following removal of the Li+. If, however, the tissue was placed in a depolarizing solution (151 mM KCL), Li+ inhibition of AII WAS NO LONGER OBSERVED. These results are interpreted to mean that Li+ interferes with an essential Ca2+-dependent step involved in membrane excitation following agonist-receptor interaction. The results are discussed in relation to a previously suggested model for AII-induced contractions in this tissue."} {"id": "PMID:1267011", "title": "Active state of normal and dystrophic mouse muscle.", "content": "Computer-controlled quick releases were used to determine the kinetics of active state tension decay in normal and dystrophic EDL muscles of the mouse (129/Re-J). Also included are measurements of the duration of the active state plateau, isometric twitch and tetanus parameters, and the stress-strain properties of the elastic elements. Alterations in the isometric tension characteristics of dystrophic muscles confirm previous investigations and indicate that dystrophic sarcomeres have a diminished ability to shorten and produce tension. The compliance of the series-elastic elements is not changed, whereas a 50% reduction in the interanl extension of the series elements is noted for dystrophic muscle. The rate of decay and maximum intensity (Po) of active state decay is reduced 60-70% in dystrophic muscles. The first-order rate constant and the total duration of the active state are not altered. These results are discussed in terms of the possible involvement of the contractile proteins and the sarcoplasmic reticulum in determining active state deficits.", "contents": "Active state of normal and dystrophic mouse muscle. Computer-controlled quick releases were used to determine the kinetics of active state tension decay in normal and dystrophic EDL muscles of the mouse (129/Re-J). Also included are measurements of the duration of the active state plateau, isometric twitch and tetanus parameters, and the stress-strain properties of the elastic elements. Alterations in the isometric tension characteristics of dystrophic muscles confirm previous investigations and indicate that dystrophic sarcomeres have a diminished ability to shorten and produce tension. The compliance of the series-elastic elements is not changed, whereas a 50% reduction in the interanl extension of the series elements is noted for dystrophic muscle. The rate of decay and maximum intensity (Po) of active state decay is reduced 60-70% in dystrophic muscles. The first-order rate constant and the total duration of the active state are not altered. These results are discussed in terms of the possible involvement of the contractile proteins and the sarcoplasmic reticulum in determining active state deficits."} {"id": "PMID:1267012", "title": "Effects of some vasodilator drugs on transcapillary fluid exchange in renal cortex.", "content": "In 23 Munich-Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intra-arterial infusions of mildly vasodepressor doses of prostaglandin E1,acetylcholine, and bradykinin. For each drug single-nephron glomerular filtration rate remained unchanged from normal hydropenic values while glomerular plasma flow rate increased, resulting in declines in single-nephron filtration fraction (SNFF). Mean glomerular transcapillary hydraulic pressure difference (delta P) increased or remained unchanged on average. Declines in SNFF were accompanied by reductions in efferent arteriolar oncotic pressure (piE). Filtration pressure equilibrium, equality between pi E and delta P, obtained before but not during drug infusions. In the latter situation values for the glomerular capillary ultrafiltration coefficient were calculated and found to be significantly reduced from published control values. Despite marked falls in pi E during drug infusion, absolute proximal reabsorption was not reduced significantly, due, it is suggested, to the opposing effects of increases in efferent arteriolar plasma flow and interstitial hydraulic pressure.", "contents": "Effects of some vasodilator drugs on transcapillary fluid exchange in renal cortex. In 23 Munich-Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intra-arterial infusions of mildly vasodepressor doses of prostaglandin E1,acetylcholine, and bradykinin. For each drug single-nephron glomerular filtration rate remained unchanged from normal hydropenic values while glomerular plasma flow rate increased, resulting in declines in single-nephron filtration fraction (SNFF). Mean glomerular transcapillary hydraulic pressure difference (delta P) increased or remained unchanged on average. Declines in SNFF were accompanied by reductions in efferent arteriolar oncotic pressure (piE). Filtration pressure equilibrium, equality between pi E and delta P, obtained before but not during drug infusions. In the latter situation values for the glomerular capillary ultrafiltration coefficient were calculated and found to be significantly reduced from published control values. Despite marked falls in pi E during drug infusion, absolute proximal reabsorption was not reduced significantly, due, it is suggested, to the opposing effects of increases in efferent arteriolar plasma flow and interstitial hydraulic pressure."} {"id": "PMID:1267013", "title": "Estimation of glucose turnover and recycling in rabbits using various [3H, 14C]glucose labels.", "content": "The glucose replacement rate, percent carbon recycling, mean glucose transit time, and the glucose mass were determined in fasted unanesthetized rabbits after administration of [2-3H,U-14C]-, [3-3H,U-14C]-, [5-3H,U-14C]- or [6-3H,U-14C]glucose using the procedures of Katz et al. (10). The glucose replacement rates and carbon recycling determined with [2-3H,U-14C] and [5-3H,U-14C]glucose are equivalent and greater than those obtained with [3-3H,U-14C]- and [6-3H,U-14C]glucose. Although the means of the glucose replacement rates and percent carbon recycling obtained using [3-3H,U-14C]- and [6-3H,U-14C]glucose are similar, greater variation resulted using the former tracer. Comparisons of detritiation rates and percent carbon recycling using [2-3H,U-14C]- and [6-3H,U-14C]glucose suggest that about 10% of tritium is lost from carbon 2 via futile cycling at the glucose 6-phosphate level. Similarly, comparisons of [5-3H,U-14C]- and [6-3H,U-14C]glucose metabolism suggest that about 10% of tritium lost from carbon 5 occurs via futile cycling at the fructose diphosphate level and/or via the transaldolase reaction. Our results indicate that [6-3H,U-14C]glucose is the more suitable tracer for determining the glucose replacement rate and carbon recycling in vivo.", "contents": "Estimation of glucose turnover and recycling in rabbits using various [3H, 14C]glucose labels. The glucose replacement rate, percent carbon recycling, mean glucose transit time, and the glucose mass were determined in fasted unanesthetized rabbits after administration of [2-3H,U-14C]-, [3-3H,U-14C]-, [5-3H,U-14C]- or [6-3H,U-14C]glucose using the procedures of Katz et al. (10). The glucose replacement rates and carbon recycling determined with [2-3H,U-14C] and [5-3H,U-14C]glucose are equivalent and greater than those obtained with [3-3H,U-14C]- and [6-3H,U-14C]glucose. Although the means of the glucose replacement rates and percent carbon recycling obtained using [3-3H,U-14C]- and [6-3H,U-14C]glucose are similar, greater variation resulted using the former tracer. Comparisons of detritiation rates and percent carbon recycling using [2-3H,U-14C]- and [6-3H,U-14C]glucose suggest that about 10% of tritium is lost from carbon 2 via futile cycling at the glucose 6-phosphate level. Similarly, comparisons of [5-3H,U-14C]- and [6-3H,U-14C]glucose metabolism suggest that about 10% of tritium lost from carbon 5 occurs via futile cycling at the fructose diphosphate level and/or via the transaldolase reaction. Our results indicate that [6-3H,U-14C]glucose is the more suitable tracer for determining the glucose replacement rate and carbon recycling in vivo."} {"id": "PMID:1267014", "title": "Effects of maleate on carbohydrate metabolism in rats.", "content": "Intraperitoneal administration of maleate produced an increase in blood alpha-ketoacid, acetoacetate, and free fatty acids. The effect of this treatment on blood glucose levels depended on whether the rats were fed or fasted. In fed rats it was accompanied by slight, transient hyperglycemia connected with depletion of liver glycogen stores. In fasted animals moderate hypoglycemia was observed. The in vivo conversion of various precursors into blood glucose was not inhibited, suggesting that maleate does not affect hepatic gluconeogenesis. Neither was a direct effect on liver glycogenolysis observed. On the other hand, maleate inhibited renal gluconeogenesis from various substrates and stimulated anerobic glycolysis in kidney cortical alices. The data are interpreted in terms of increased utilization and decreased production of glucose by the kidney followed by secondary changes in liver carbohydrate metabolism.", "contents": "Effects of maleate on carbohydrate metabolism in rats. Intraperitoneal administration of maleate produced an increase in blood alpha-ketoacid, acetoacetate, and free fatty acids. The effect of this treatment on blood glucose levels depended on whether the rats were fed or fasted. In fed rats it was accompanied by slight, transient hyperglycemia connected with depletion of liver glycogen stores. In fasted animals moderate hypoglycemia was observed. The in vivo conversion of various precursors into blood glucose was not inhibited, suggesting that maleate does not affect hepatic gluconeogenesis. Neither was a direct effect on liver glycogenolysis observed. On the other hand, maleate inhibited renal gluconeogenesis from various substrates and stimulated anerobic glycolysis in kidney cortical alices. The data are interpreted in terms of increased utilization and decreased production of glucose by the kidney followed by secondary changes in liver carbohydrate metabolism."} {"id": "PMID:1267015", "title": "Kidney pressures after temporary renal artery occlusion in the rat.", "content": "Acute kidney failure was produced in the anesthetized rat by 1 h of complete renal artery occlusion. Kidney function was studied either immediately after release of the occlusion or 1 day later using clearance, micropuncture, histological, and nephron dissection techniques. Polyfructosan clearance was decreased to 5% of normal after temporary occlusion. Proximal tubular pressure (PTP) averaged 13-14 mmHg in normal kidneys, 39 mmHg immediately after release of unilateral occlusion, 19 mmHg 1 day after unilateral occlusion, and 25 mmHg 1 day after bilateral occlusion. The increased PTP reduces the glomerular filtration rate (GFR). Glomerular capillary pressure, estimated from the sum of the stop-flow and arterial plasma colloid osmotic pressures, was not decreased after temporary ischemia. Single-nephron GFR, measured without intratubular pressure control, was only slightly below normal 1 day after bilateral occlusion. Most distal tubules from ischemia-damaged kidneys contained hyaline casts. Tubular obstruction is a major factor in this model of acute kidney failure.", "contents": "Kidney pressures after temporary renal artery occlusion in the rat. Acute kidney failure was produced in the anesthetized rat by 1 h of complete renal artery occlusion. Kidney function was studied either immediately after release of the occlusion or 1 day later using clearance, micropuncture, histological, and nephron dissection techniques. Polyfructosan clearance was decreased to 5% of normal after temporary occlusion. Proximal tubular pressure (PTP) averaged 13-14 mmHg in normal kidneys, 39 mmHg immediately after release of unilateral occlusion, 19 mmHg 1 day after unilateral occlusion, and 25 mmHg 1 day after bilateral occlusion. The increased PTP reduces the glomerular filtration rate (GFR). Glomerular capillary pressure, estimated from the sum of the stop-flow and arterial plasma colloid osmotic pressures, was not decreased after temporary ischemia. Single-nephron GFR, measured without intratubular pressure control, was only slightly below normal 1 day after bilateral occlusion. Most distal tubules from ischemia-damaged kidneys contained hyaline casts. Tubular obstruction is a major factor in this model of acute kidney failure."} {"id": "PMID:1267016", "title": "Open-loop respiratory chemosensitivity in chickens and ducks.", "content": "In order to study the behavior of the avian respiratory center under open-loop conditions, recordings of respiratory motor discharges were made from an intercostal nerve in a unidirectionally ventilated paralyzed preparation during normoxic hypercapnia, hypoxic normocapnia and asphyxia, and under control conditions. Respiratory motor burst rate (RMBR) in ducks showed a maximum at 40 mmHg Paco2 with depression at higher and lower values, both in the steady state and during rapid transients. RMBR was apparently independent of Paco2 in chickens, and of Pao2 in both species. During asphyxia, RMBR in ducks fell steadily while the number of spikes in each burst did not change. RMBR during asphyxia bore the same relationship to Paco2 as during unidirectional ventilation. Chickens did not respond consistently to asphyxia, but RMBR tended to increase and, in some cases, the number of spikes per burst also increased. Possible mechanisms and functions of the asphyxic respiratory depression observed in ducks are discussed.", "contents": "Open-loop respiratory chemosensitivity in chickens and ducks. In order to study the behavior of the avian respiratory center under open-loop conditions, recordings of respiratory motor discharges were made from an intercostal nerve in a unidirectionally ventilated paralyzed preparation during normoxic hypercapnia, hypoxic normocapnia and asphyxia, and under control conditions. Respiratory motor burst rate (RMBR) in ducks showed a maximum at 40 mmHg Paco2 with depression at higher and lower values, both in the steady state and during rapid transients. RMBR was apparently independent of Paco2 in chickens, and of Pao2 in both species. During asphyxia, RMBR in ducks fell steadily while the number of spikes in each burst did not change. RMBR during asphyxia bore the same relationship to Paco2 as during unidirectional ventilation. Chickens did not respond consistently to asphyxia, but RMBR tended to increase and, in some cases, the number of spikes per burst also increased. Possible mechanisms and functions of the asphyxic respiratory depression observed in ducks are discussed."} {"id": "PMID:1267017", "title": "A comparative study of pulsatile arterial hemodynamics in rabbits and guinea pigs.", "content": "Pulsatile pressure and flow were measured in the ascending aorta and other arteries of 22 anesthetized rabbits and 16 anesthetized guinea pigs. Pressure/flow relationships were expressed as vascular impedance. Aortic flow waves were almost identical in the two species, but pressure waves were quite different. Reflected pressure waves returned earlier from the periphery in guinea pigs, augmenting pressure during late systole and resulting in relatively high external left ventricular work, an inappropriately larger difference between mean systolic and mean diastolic pressure and absence of any aortic diastolic pressure wave. Values of impedance modulus and phase were similar but differed in the frequency at which maxima and minima occurred. In both species, impedance curves were interpreted to indicate a functionally discrete reflecting site in the lower body whose position corresponded to the region of the aortic bifurcation. In addition, rabbits showed evidence of an upper body reflecting site approximately one-third as far distant from the heart. As in dogs, the arterial system in both species can be represented by an asymmetrical T-shaped model of realistic dimensions.", "contents": "A comparative study of pulsatile arterial hemodynamics in rabbits and guinea pigs. Pulsatile pressure and flow were measured in the ascending aorta and other arteries of 22 anesthetized rabbits and 16 anesthetized guinea pigs. Pressure/flow relationships were expressed as vascular impedance. Aortic flow waves were almost identical in the two species, but pressure waves were quite different. Reflected pressure waves returned earlier from the periphery in guinea pigs, augmenting pressure during late systole and resulting in relatively high external left ventricular work, an inappropriately larger difference between mean systolic and mean diastolic pressure and absence of any aortic diastolic pressure wave. Values of impedance modulus and phase were similar but differed in the frequency at which maxima and minima occurred. In both species, impedance curves were interpreted to indicate a functionally discrete reflecting site in the lower body whose position corresponded to the region of the aortic bifurcation. In addition, rabbits showed evidence of an upper body reflecting site approximately one-third as far distant from the heart. As in dogs, the arterial system in both species can be represented by an asymmetrical T-shaped model of realistic dimensions."} {"id": "PMID:1267018", "title": "Ouabain-mediated sodium uptake and bile formation by isolated perfused rat liver.", "content": "Ouabain exhibits a dose-dependent choleretic effect in the isolated perfused rat liver. Its uptake from the perfusate into the liver is maintained against a concentration gradient and becomes clearly saturated at higher perfusate concentrations. A low extracellular sodium concentration inhibits the rate of ouabain transfer into liver cells, resulting in a marked decrease of the maximal transport rate. Dibucaine completely abolishes the uptake of the glycoside by the isolated liver. Determination of Na-22 tracer fluxes suggests that ouabain uptake is accompanied by a net flux of sodium into the cell, which seems to be due to a cotransport of sodium with ouabain rather than to the inhibition of the sinusoidal Na+ -K+ -ATPase. Sodium introduced into the cell in this way apparently is extruded into the bile canaliculi. The increase of isotonic bile flow, which is simultaneously observed, points to a dilution of the canalicular sodium gradient by water and electrolytes through an intercellular pathway. Our results present further evidence that bile secretion is controlled by transcellular sodium movements.", "contents": "Ouabain-mediated sodium uptake and bile formation by isolated perfused rat liver. Ouabain exhibits a dose-dependent choleretic effect in the isolated perfused rat liver. Its uptake from the perfusate into the liver is maintained against a concentration gradient and becomes clearly saturated at higher perfusate concentrations. A low extracellular sodium concentration inhibits the rate of ouabain transfer into liver cells, resulting in a marked decrease of the maximal transport rate. Dibucaine completely abolishes the uptake of the glycoside by the isolated liver. Determination of Na-22 tracer fluxes suggests that ouabain uptake is accompanied by a net flux of sodium into the cell, which seems to be due to a cotransport of sodium with ouabain rather than to the inhibition of the sinusoidal Na+ -K+ -ATPase. Sodium introduced into the cell in this way apparently is extruded into the bile canaliculi. The increase of isotonic bile flow, which is simultaneously observed, points to a dilution of the canalicular sodium gradient by water and electrolytes through an intercellular pathway. Our results present further evidence that bile secretion is controlled by transcellular sodium movements."} {"id": "PMID:1267019", "title": "Absence of fetal placental waterfall phenomenon in chronically prepared fetal lambs.", "content": "An electromagnetic flow sensor was placed on the distal fetal aorta (umbilical flow fraction 78.1 +/- 1.6 SEM, %), an inflatable occluder was tied around the umbilical cord, and catheters were placed in distal branches of an umbilical artery and vein, a uterine vein, and in the amniotic cavity. An inflatalbe occluder was tied around the vagina of some of the ewes. Control values 3 days after surgery were (mean +/- SE): fetal femoral artery pH, 7.37 +/- 0.01; umbilical blood flow, 186 +/- 14 ml-min-1 .kg fetus-1; fetal arterial blood pressure, 39 +/- 3 mmHg; and umbilical venous pressure, 7.4 +/- 1.0 mmHg (above intrauterine pressure). Fetal weight at autopsy was 3.1 +/- 0.3 kg, n = 11. Small increases in umbilical vein pressure caused immediate decreases in placental blood flow without decreases in fetal arterial blood pressure. The relation between venous pressure and umbilical blood flow at constant arterial pressure was that of an inert system, i.e., no evidence of a surrounding pressure (Starling resistor effect or waterfall phenomenon) could be found with increases in venous pressures of 2-40 mmHg. The results were not affected by increases in uterine vein pressure between 2 and 30 mmHg, nor by anesthesia and supine position of the ewe, nor by ganglionic blockade of the fetal ANS. It was concluded that surrounding pressures in the fetal placental circulation could not be demonstrated.", "contents": "Absence of fetal placental waterfall phenomenon in chronically prepared fetal lambs. An electromagnetic flow sensor was placed on the distal fetal aorta (umbilical flow fraction 78.1 +/- 1.6 SEM, %), an inflatable occluder was tied around the umbilical cord, and catheters were placed in distal branches of an umbilical artery and vein, a uterine vein, and in the amniotic cavity. An inflatalbe occluder was tied around the vagina of some of the ewes. Control values 3 days after surgery were (mean +/- SE): fetal femoral artery pH, 7.37 +/- 0.01; umbilical blood flow, 186 +/- 14 ml-min-1 .kg fetus-1; fetal arterial blood pressure, 39 +/- 3 mmHg; and umbilical venous pressure, 7.4 +/- 1.0 mmHg (above intrauterine pressure). Fetal weight at autopsy was 3.1 +/- 0.3 kg, n = 11. Small increases in umbilical vein pressure caused immediate decreases in placental blood flow without decreases in fetal arterial blood pressure. The relation between venous pressure and umbilical blood flow at constant arterial pressure was that of an inert system, i.e., no evidence of a surrounding pressure (Starling resistor effect or waterfall phenomenon) could be found with increases in venous pressures of 2-40 mmHg. The results were not affected by increases in uterine vein pressure between 2 and 30 mmHg, nor by anesthesia and supine position of the ewe, nor by ganglionic blockade of the fetal ANS. It was concluded that surrounding pressures in the fetal placental circulation could not be demonstrated."} {"id": "PMID:1267020", "title": "Interaction of interval-force relationship with aortic pressure and stroke volume.", "content": "The modification by aortic pressure and stroke volume of the response in cardiac performance to increases in heart rate (interval-force relationship) has not been previously studied. To investigate this interaction, 30 adrenergically blocked anesthetized dogs on right heart bypass were studied. At constant low aortic pressure and stroke volume, increasing heart rate (over the entire range 60-180) is associated with a continuously increasing stroke power, decreasing systolic ejection period, and an unchanging left ventricular end-diastolic pressure and circumference. At increased aortic pressure or stroke volume at low rates (60-120), increases in heart rate were associated with an increased performance. However, at increased aortic pressure or stroke volume at high rates (120-180), increases in heart rate were associated with a leveling or decrease in performance. Thus, an increase in aortic pressure or stroke volume results in an accentuation of the improvement in cardiac performance observed with increases in heart rate, but this response is limited to a low heart rate range. Therefore, the hemodynamic response to given increases in heart rate is critically dependent on aortic pressure and stroke volume.", "contents": "Interaction of interval-force relationship with aortic pressure and stroke volume. The modification by aortic pressure and stroke volume of the response in cardiac performance to increases in heart rate (interval-force relationship) has not been previously studied. To investigate this interaction, 30 adrenergically blocked anesthetized dogs on right heart bypass were studied. At constant low aortic pressure and stroke volume, increasing heart rate (over the entire range 60-180) is associated with a continuously increasing stroke power, decreasing systolic ejection period, and an unchanging left ventricular end-diastolic pressure and circumference. At increased aortic pressure or stroke volume at low rates (60-120), increases in heart rate were associated with an increased performance. However, at increased aortic pressure or stroke volume at high rates (120-180), increases in heart rate were associated with a leveling or decrease in performance. Thus, an increase in aortic pressure or stroke volume results in an accentuation of the improvement in cardiac performance observed with increases in heart rate, but this response is limited to a low heart rate range. Therefore, the hemodynamic response to given increases in heart rate is critically dependent on aortic pressure and stroke volume."} {"id": "PMID:1267021", "title": "Effects of azotemia on renal extraction and clearance of PAH and TEA.", "content": "Dogs were made azotemic by bilateral ureteral-venous anastomosis. Subsequently, the left ureter, a systemic artery, and the left renal vein were cannulated. Left renal blood flow (RBF) was measured by an electromagnetic flowmeter. Left renal clearances and extractions of [14C]tetraethylammonium ([14C]TEA) and p-aminohippuric acid (PAH) were determined at five 40-min intervals after administraiton of loading doses and institution of a maintenance infusion containing PAH and [14C]TEA. The renal extraction of TEA was independent of blood urea nitrogen (BUN), whereas the extraction of PAH correlated inversely with BUN. Renal plasma flows calculated from urinary clearances and renal extractions agreed with renal plasma flows calculated from flowmeter data. The extraction of TEA remained constant over the 200-min experimental period, whereas the extraction of PAH increases progressively as a function of time. It is probable that those organic acids which accumulate in azotemia, and interfered with renal tubular secretion of PAH, were themselves eliminated after opening the ureteral-venous anastomosis. Thus, TEA is superior to PAH for evaluation of the renal circulation in azotemia.", "contents": "Effects of azotemia on renal extraction and clearance of PAH and TEA. Dogs were made azotemic by bilateral ureteral-venous anastomosis. Subsequently, the left ureter, a systemic artery, and the left renal vein were cannulated. Left renal blood flow (RBF) was measured by an electromagnetic flowmeter. Left renal clearances and extractions of [14C]tetraethylammonium ([14C]TEA) and p-aminohippuric acid (PAH) were determined at five 40-min intervals after administraiton of loading doses and institution of a maintenance infusion containing PAH and [14C]TEA. The renal extraction of TEA was independent of blood urea nitrogen (BUN), whereas the extraction of PAH correlated inversely with BUN. Renal plasma flows calculated from urinary clearances and renal extractions agreed with renal plasma flows calculated from flowmeter data. The extraction of TEA remained constant over the 200-min experimental period, whereas the extraction of PAH increases progressively as a function of time. It is probable that those organic acids which accumulate in azotemia, and interfered with renal tubular secretion of PAH, were themselves eliminated after opening the ureteral-venous anastomosis. Thus, TEA is superior to PAH for evaluation of the renal circulation in azotemia."} {"id": "PMID:1267022", "title": "Short-loop feedback control of luteinizing hormone in the rabbit.", "content": "A radioimmunoassay for rabbit luteinizing hormone (rLH) in which rLH shows no significant cross-reaction with human LH (hLH) or human chorionic gonadotropin (HCG) was employed to test for the existence of a short-loop feedback for LH in the rabbit. Two weeks after castration, hCG and hLH were administered intravenously to rabbits, and the effects on circulating rLH were measured. Purified hLH (10 ng or 100 IU) produced significant depression of blood rLH within 30-60 min of intravenous injection. Saline administered to the same animals produced no changes in rLH. Injection of hCG (2,000 IU) under the same conditions also produced a significant fall in rLH. However, hCG administered to rabbits castrated 6 wk prior to study failed to suppress endogenous rLH. These data demonstrate, by direct radioimmunoassay quantification of blood hormones, the existence of a short-loop negative feedback for LH in the rabbit. They also suggest that the sensitivity of the short-loop changes with time after castration.", "contents": "Short-loop feedback control of luteinizing hormone in the rabbit. A radioimmunoassay for rabbit luteinizing hormone (rLH) in which rLH shows no significant cross-reaction with human LH (hLH) or human chorionic gonadotropin (HCG) was employed to test for the existence of a short-loop feedback for LH in the rabbit. Two weeks after castration, hCG and hLH were administered intravenously to rabbits, and the effects on circulating rLH were measured. Purified hLH (10 ng or 100 IU) produced significant depression of blood rLH within 30-60 min of intravenous injection. Saline administered to the same animals produced no changes in rLH. Injection of hCG (2,000 IU) under the same conditions also produced a significant fall in rLH. However, hCG administered to rabbits castrated 6 wk prior to study failed to suppress endogenous rLH. These data demonstrate, by direct radioimmunoassay quantification of blood hormones, the existence of a short-loop negative feedback for LH in the rabbit. They also suggest that the sensitivity of the short-loop changes with time after castration."} {"id": "PMID:1267023", "title": "Neurally mediated increase in mitosis and DNA of rat parotid with increase in bulk of diet.", "content": "A transient burst of mitosis was induced in rat parotid gland 2 days after change from a diet of solid chow only to one consisting of 50% inert cellulose and 50% solid chow (bulk diet). Mitosis was thus induced when glandular activity was changed from normal levels (solid chow) to levels greater than normal (bulk diet). Elimination of either autonomic pathway inhibited the mitotic response, but elimination of the parasympathetic had the greater inhibitory influence. The burst of mitosis induced by bulk diet was followed by increases in total DNA (16%), RNA (24%) and weight (27%) of the gland 2 wk after the dietary change. These changes did not occur when both autonomic pathways were, or only the parasympathetic was, removed immediately prior to the dietary change. Effects of sympathectomy were less pronounced. The parasympathetic innervation has the principal role in regulation of mitosis, cell number and size, and nucleic acid content when glandular activity is increased above normal by physiological means.", "contents": "Neurally mediated increase in mitosis and DNA of rat parotid with increase in bulk of diet. A transient burst of mitosis was induced in rat parotid gland 2 days after change from a diet of solid chow only to one consisting of 50% inert cellulose and 50% solid chow (bulk diet). Mitosis was thus induced when glandular activity was changed from normal levels (solid chow) to levels greater than normal (bulk diet). Elimination of either autonomic pathway inhibited the mitotic response, but elimination of the parasympathetic had the greater inhibitory influence. The burst of mitosis induced by bulk diet was followed by increases in total DNA (16%), RNA (24%) and weight (27%) of the gland 2 wk after the dietary change. These changes did not occur when both autonomic pathways were, or only the parasympathetic was, removed immediately prior to the dietary change. Effects of sympathectomy were less pronounced. The parasympathetic innervation has the principal role in regulation of mitosis, cell number and size, and nucleic acid content when glandular activity is increased above normal by physiological means."} {"id": "PMID:1267024", "title": "Intestinal villus blood flow measured with carbon monoxide and microspheres.", "content": "The purpose of the present study was to compare the small intestinal blood flow that equilibrates with luminal CO (FLco) with simultaneous determinations of villus blood flow measured by a recent modification of the microsphere technique. These studies, carried out in rabbits, showed that FLco closely correlated (r = 0.83) with villus flow measured with microspheres over a three-fold range of flows, and the mean rate of flow to the villi by both techniques was about 0.08 ml/min X g of intestine. Thus, FLco appears to be a measure of villus blood flow. Based on previous studies of inert gas uptake from the rabbit small intestine, it appears that absorption of readily diffusible substances in the rabbit can be represented by a simple two-component model: a flow-limited component in which substances equilibrate with villus blood flow and are carried away without subsequent countercurrent exchange, and a diffusion-limited component which presumably represents uptake by the blood flow of the crypt region or submucosa.", "contents": "Intestinal villus blood flow measured with carbon monoxide and microspheres. The purpose of the present study was to compare the small intestinal blood flow that equilibrates with luminal CO (FLco) with simultaneous determinations of villus blood flow measured by a recent modification of the microsphere technique. These studies, carried out in rabbits, showed that FLco closely correlated (r = 0.83) with villus flow measured with microspheres over a three-fold range of flows, and the mean rate of flow to the villi by both techniques was about 0.08 ml/min X g of intestine. Thus, FLco appears to be a measure of villus blood flow. Based on previous studies of inert gas uptake from the rabbit small intestine, it appears that absorption of readily diffusible substances in the rabbit can be represented by a simple two-component model: a flow-limited component in which substances equilibrate with villus blood flow and are carried away without subsequent countercurrent exchange, and a diffusion-limited component which presumably represents uptake by the blood flow of the crypt region or submucosa."} {"id": "PMID:1267025", "title": "Heat loss from feet of herring gulls at rest and during flight.", "content": "The role of the feet of herring gulls (Larus argentatus) in heat dissipation was estimated during rest and wind-tunnel flight. We determined the blood flow to the feet and the arteriovenous temperature difference and thus estimated heat loss from the feet. Determinations of oxygen consumption and respiratory water loss at rest gave a heat production of about 8 W; 37-56% of this heat was lost from the feet (air temp = 10-35 degrees C). During flight heat production was estimated to be about 57 W and heat loss from the feet was 46 W, about 80% of the heat production in flight. Thus the webbed feet are an important avenue of heat loss in the herring gull.", "contents": "Heat loss from feet of herring gulls at rest and during flight. The role of the feet of herring gulls (Larus argentatus) in heat dissipation was estimated during rest and wind-tunnel flight. We determined the blood flow to the feet and the arteriovenous temperature difference and thus estimated heat loss from the feet. Determinations of oxygen consumption and respiratory water loss at rest gave a heat production of about 8 W; 37-56% of this heat was lost from the feet (air temp = 10-35 degrees C). During flight heat production was estimated to be about 57 W and heat loss from the feet was 46 W, about 80% of the heat production in flight. Thus the webbed feet are an important avenue of heat loss in the herring gull."} {"id": "PMID:1267026", "title": "Intracellular osmoregulatory role of amino acids and urea in marine elasmobranchs.", "content": "Little skates, Raja erinacea, and stingrays, Dasyatis americana, were gradually transferred over a period of 4-5 days from full strength to approximatley 50% seawater. Plasma and muscle osmolarity fell. Hematocrits were essentially unchanged. Extracellular fluid volume (ECF) of muscle, estimated as the chloride space, increased 70% during this period. Regulation of muscle cell volume was associated with sharp declines in cellular concentrations of total amino acids (ninhydrin-positive materials) and urea. The osmoregulatory importance of the free amino acid pool in erythrocytes and muscle was a particularly prominent feature in both species. Intracellular amino acid concentration in R. erinacea muscle fell from 214 to 144 mmol/liter during transfer to 50% seawater, urea from 398 to 264, and trimethylamine oxide (TMAO) dropped from 63.9 to 35.8 mmol/liter. TMAO plasma levels were similar in stingray and skate, but muscle TMAO concentrations were much higher in the former. Urea content in stingray plasma greatly exceeded that in R. erinacea-630 and 574 mmol/liter in two specimens-perhaps the highest recorded.", "contents": "Intracellular osmoregulatory role of amino acids and urea in marine elasmobranchs. Little skates, Raja erinacea, and stingrays, Dasyatis americana, were gradually transferred over a period of 4-5 days from full strength to approximatley 50% seawater. Plasma and muscle osmolarity fell. Hematocrits were essentially unchanged. Extracellular fluid volume (ECF) of muscle, estimated as the chloride space, increased 70% during this period. Regulation of muscle cell volume was associated with sharp declines in cellular concentrations of total amino acids (ninhydrin-positive materials) and urea. The osmoregulatory importance of the free amino acid pool in erythrocytes and muscle was a particularly prominent feature in both species. Intracellular amino acid concentration in R. erinacea muscle fell from 214 to 144 mmol/liter during transfer to 50% seawater, urea from 398 to 264, and trimethylamine oxide (TMAO) dropped from 63.9 to 35.8 mmol/liter. TMAO plasma levels were similar in stingray and skate, but muscle TMAO concentrations were much higher in the former. Urea content in stingray plasma greatly exceeded that in R. erinacea-630 and 574 mmol/liter in two specimens-perhaps the highest recorded."} {"id": "PMID:1267027", "title": "Thermal homeostasis in rats after intrahypothalamic injections of 6-hyroxydopamine.", "content": "Specific destruction of at least 90% of the noradrenergic neurons in the preoptic/anterior hypothalamic region (PO/AH) by local injection of 9-hyroxydopamine (6-HDA) did not disrupt thermoregulation by rats either in the heat or the cold. Examination of the multiple effector mechanisms suggested that thermal balance was maintained in a normal fashion, and that compensatory adjustments did not conceal individual dysfunctions. In contrast with the ineffectual 6-HDA lesions of the PO/AH were the outstanding impairments seen in rats following electrolytic lesions of this area. All the latter animals became severely hyperthermic during the 1st h of exposure to an ambient temperature of 40 degrees C, and half of them were additionally unable to maintain body temperatures when exposed to an ambient temperature of 6 degrees C. The electrolytic lesions reduced norepinephrine levels in the PO/AH, but the 50-70% depletions were substantially smaller than those found in 6-HDA-treated rats. These results raise new doubts about whether central noradrenergic fibers have an important role in the regulation of body temperature by rats.", "contents": "Thermal homeostasis in rats after intrahypothalamic injections of 6-hyroxydopamine. Specific destruction of at least 90% of the noradrenergic neurons in the preoptic/anterior hypothalamic region (PO/AH) by local injection of 9-hyroxydopamine (6-HDA) did not disrupt thermoregulation by rats either in the heat or the cold. Examination of the multiple effector mechanisms suggested that thermal balance was maintained in a normal fashion, and that compensatory adjustments did not conceal individual dysfunctions. In contrast with the ineffectual 6-HDA lesions of the PO/AH were the outstanding impairments seen in rats following electrolytic lesions of this area. All the latter animals became severely hyperthermic during the 1st h of exposure to an ambient temperature of 40 degrees C, and half of them were additionally unable to maintain body temperatures when exposed to an ambient temperature of 6 degrees C. The electrolytic lesions reduced norepinephrine levels in the PO/AH, but the 50-70% depletions were substantially smaller than those found in 6-HDA-treated rats. These results raise new doubts about whether central noradrenergic fibers have an important role in the regulation of body temperature by rats."} {"id": "PMID:1267028", "title": "Effect of carotid sinus nerve stimulation pattern on cardiorespiratory responses.", "content": "The reflex responses to steady and intermittent stimulation of the carotid sinus nerve (CSN) were compared in anesthetized dogs. Intermittent stimulation was less effective than steady stimulation in reducing the arterial blood pressure, and the disparity was exaggerated after acute sinoaortic denervation. With the sinoaortic nerves intact, at low mean stimulation frequencies the heart rate responses were greater during intermittent than during steady CSN stimulation. At higher mean stimulation frequencies, however, steady CSN stimuli were more effective than were the intermittent type. After sinoaortic denervation, steady stimuli evoked greater heart rate responses than did intermittent stimuli over the entire mean frequency range studied. Reflex changes in respiratory depth and frequency were also greater during steady than during intermittent CSN stimulation. The greater efficacy of steady than of intermittent stimulation in evoking.the observed reflex cardiovascular and respiratory changes is probably ascribable to the pronounced frequency limitation at the first synapse of the baroreceptor reflex in the brain.", "contents": "Effect of carotid sinus nerve stimulation pattern on cardiorespiratory responses. The reflex responses to steady and intermittent stimulation of the carotid sinus nerve (CSN) were compared in anesthetized dogs. Intermittent stimulation was less effective than steady stimulation in reducing the arterial blood pressure, and the disparity was exaggerated after acute sinoaortic denervation. With the sinoaortic nerves intact, at low mean stimulation frequencies the heart rate responses were greater during intermittent than during steady CSN stimulation. At higher mean stimulation frequencies, however, steady CSN stimuli were more effective than were the intermittent type. After sinoaortic denervation, steady stimuli evoked greater heart rate responses than did intermittent stimuli over the entire mean frequency range studied. Reflex changes in respiratory depth and frequency were also greater during steady than during intermittent CSN stimulation. The greater efficacy of steady than of intermittent stimulation in evoking.the observed reflex cardiovascular and respiratory changes is probably ascribable to the pronounced frequency limitation at the first synapse of the baroreceptor reflex in the brain."} {"id": "PMID:1267029", "title": "Biliary secretion in elasmobranchs. II. Hepatic uptake and biliary excretion of organic anions.", "content": "[35S]Bromosulfophthalein ([35C]BSP), [14C]sodium taurocholate ([14C]NaTC), AND 10 MG OF UNLABELED BSP.and of phenol-3,6-dibromophthalein disulfonate (DBSP) per kilogram body weight were injected in the caudal artery of free-swimming dogfish sharks (Squalus acanthias) and small skates (Raja erinacea). Twenty-four hours later, 85.8 +/- 15.7% of [35S]BSP was recovered in bile and liver in dogfish and 78.4 +/- 9.9% in skates. Similar results were obtained for [14C]NaTC. Unlabeled BSP or DBSP (10 mg/kg body wt) were also selectively excreted in bile over a 4-day period and at comparable rates in both species. More than 85% of [35S]BSP, BSP, and DBSP in bile was in unconjugated form. Selective hepatic clearance of BSP occurred despite nonselective binding to liver homogenates and very low concentrations of binding proteins in liver cytosol. Analysis of the organic anion plasma disappearance curves suggest that the clearance of anions into bile in elasmobranchs is delayed disproportionately relative to hepatic uptake. Albumin-BSP infusions did not prevent selective hepatic uptake of [35S]BSP, although biliary excretion was delayed further. These studies demonstrate that transport systems for biliary excretion of organic anions evolved prior to migration of marine life from the sea and relatively independently of intrahepatic conjugation and organic anion-binding proteins.", "contents": "Biliary secretion in elasmobranchs. II. Hepatic uptake and biliary excretion of organic anions. [35S]Bromosulfophthalein ([35C]BSP), [14C]sodium taurocholate ([14C]NaTC), AND 10 MG OF UNLABELED BSP.and of phenol-3,6-dibromophthalein disulfonate (DBSP) per kilogram body weight were injected in the caudal artery of free-swimming dogfish sharks (Squalus acanthias) and small skates (Raja erinacea). Twenty-four hours later, 85.8 +/- 15.7% of [35S]BSP was recovered in bile and liver in dogfish and 78.4 +/- 9.9% in skates. Similar results were obtained for [14C]NaTC. Unlabeled BSP or DBSP (10 mg/kg body wt) were also selectively excreted in bile over a 4-day period and at comparable rates in both species. More than 85% of [35S]BSP, BSP, and DBSP in bile was in unconjugated form. Selective hepatic clearance of BSP occurred despite nonselective binding to liver homogenates and very low concentrations of binding proteins in liver cytosol. Analysis of the organic anion plasma disappearance curves suggest that the clearance of anions into bile in elasmobranchs is delayed disproportionately relative to hepatic uptake. Albumin-BSP infusions did not prevent selective hepatic uptake of [35S]BSP, although biliary excretion was delayed further. These studies demonstrate that transport systems for biliary excretion of organic anions evolved prior to migration of marine life from the sea and relatively independently of intrahepatic conjugation and organic anion-binding proteins."} {"id": "PMID:1267030", "title": "Hypophysectomy and regulation of body weight in the genetically obese Zucker rat.", "content": "Genetically obese Zucker \"fatty\" rats (fa/fa) and nonobese siblings were weighed regularly from 7 to 150 days of age to determine the onset and time course of the excessive weight gain that characterized the fatty rat. At 150 days of age, male and female fatties and their lean littermates were sham operated or hypophysectomized to examine the role of the pituitary in the fatty obesity. The operated animals were then weighed until sacrifice at 220 days of age, when adrenal weights, gonadal weights, uterine weights, and the Lee Index were determined. Fatty rats were significantly heavier than their nonobese littermates even in the 2nd wk of life (day 7-13). Complete hypophysectomy blocked the continued development of the fatty obesity but did not eliminate the adiposity established prior to hypophysectomy. It is concluded that the pituitary and the major endocrine pathways it controls are not the locus of the primary genetic lesion responsible for maintaining the Zucker fatty rat obesity.", "contents": "Hypophysectomy and regulation of body weight in the genetically obese Zucker rat. Genetically obese Zucker \"fatty\" rats (fa/fa) and nonobese siblings were weighed regularly from 7 to 150 days of age to determine the onset and time course of the excessive weight gain that characterized the fatty rat. At 150 days of age, male and female fatties and their lean littermates were sham operated or hypophysectomized to examine the role of the pituitary in the fatty obesity. The operated animals were then weighed until sacrifice at 220 days of age, when adrenal weights, gonadal weights, uterine weights, and the Lee Index were determined. Fatty rats were significantly heavier than their nonobese littermates even in the 2nd wk of life (day 7-13). Complete hypophysectomy blocked the continued development of the fatty obesity but did not eliminate the adiposity established prior to hypophysectomy. It is concluded that the pituitary and the major endocrine pathways it controls are not the locus of the primary genetic lesion responsible for maintaining the Zucker fatty rat obesity."} {"id": "PMID:1267031", "title": "Free fatty acids and albumin as mediators of thrombin-stimulated fibrinogen synthesis.", "content": "Mobilization of FFA in mice, triggered with an injection of thrombin, was followed within 24 h by a 2.5-fold increase in fibrinogen synthesis and a 30% increase in plasma fibrinogen concentration. In mouse liver slices, incubated in plasma, additions of palmitate or stearate in amounts similar to those expected in vivo in FFA mobilization stimulated fibrinogen synthesis 5.6- to 6.1-fold while unsaturated and short-chain FFA were less effective. Palmitate and linoleate also augmented albumin synthesis although not as stongly as fibrinogen synthesis. These observations raised the possibility that the greater effectiveness of saturated FFA in stimulating fibrinogen synthesis may reflect higher FFA/albumin ratios within hepatocytes in the presence of saturated FFA. Injection of exogenous defatted albumin into mice before thrombin injection prevented the FFA-associated rise in fibrinogen synthesis and plasma concentration. In incubated liver slices, defatted albumin abolished the FFA stimulation of fibrinogen synthesis when FFA/albumin ratios were maintained to the physiological range. These studies indicate that the FFA/ALBUMIN RATIO MAY PLAY A MAJOR ROLE IN THE REPLENISHMENT OF FIBRINOGEN AFTER PERIODS OF RAPID DEFIBRINOGENATION.", "contents": "Free fatty acids and albumin as mediators of thrombin-stimulated fibrinogen synthesis. Mobilization of FFA in mice, triggered with an injection of thrombin, was followed within 24 h by a 2.5-fold increase in fibrinogen synthesis and a 30% increase in plasma fibrinogen concentration. In mouse liver slices, incubated in plasma, additions of palmitate or stearate in amounts similar to those expected in vivo in FFA mobilization stimulated fibrinogen synthesis 5.6- to 6.1-fold while unsaturated and short-chain FFA were less effective. Palmitate and linoleate also augmented albumin synthesis although not as stongly as fibrinogen synthesis. These observations raised the possibility that the greater effectiveness of saturated FFA in stimulating fibrinogen synthesis may reflect higher FFA/albumin ratios within hepatocytes in the presence of saturated FFA. Injection of exogenous defatted albumin into mice before thrombin injection prevented the FFA-associated rise in fibrinogen synthesis and plasma concentration. In incubated liver slices, defatted albumin abolished the FFA stimulation of fibrinogen synthesis when FFA/albumin ratios were maintained to the physiological range. These studies indicate that the FFA/ALBUMIN RATIO MAY PLAY A MAJOR ROLE IN THE REPLENISHMENT OF FIBRINOGEN AFTER PERIODS OF RAPID DEFIBRINOGENATION."} {"id": "PMID:1267032", "title": "Women in psychiatry: a review.", "content": "Throughout the world, psychiatry is in a period of accelerated transition. In each nation the role of women in psychiatry, and the role of psychiatry in the lives of women, reflect one aspect of the development of egalitarianism. Women psychiatrists have perennially been confronted with conflicts between their professional and private life responsibilities. Internationally, the external and internal factors that prohibit or limit women's personal development and vocational participation are being scrutinized. American psychiatry is proving to be a pioneer among medical specialities in this area.", "contents": "Women in psychiatry: a review. Throughout the world, psychiatry is in a period of accelerated transition. In each nation the role of women in psychiatry, and the role of psychiatry in the lives of women, reflect one aspect of the development of egalitarianism. Women psychiatrists have perennially been confronted with conflicts between their professional and private life responsibilities. Internationally, the external and internal factors that prohibit or limit women's personal development and vocational participation are being scrutinized. American psychiatry is proving to be a pioneer among medical specialities in this area."} {"id": "PMID:1267033", "title": "Lithium in the treatment of depression.", "content": "The author reviews the studies of lithium as an antidepressant, evaluates the evidence that there might be specific subgroup of patients for whom it is effective, and reports a study he and his associates conducted that found lithium to be effective for 13 of 21 depressed patients. He concludes that there is convincing, although not conclusive, evidence for an antidepressant effect of lithium and that only by identifying the subgroup of patients for whom it is effective can the continuing uncertainty surrounding lithium's role in affective disorder be resolved. He also calls for a reevaluation of the relationship between mania and depression.", "contents": "Lithium in the treatment of depression. The author reviews the studies of lithium as an antidepressant, evaluates the evidence that there might be specific subgroup of patients for whom it is effective, and reports a study he and his associates conducted that found lithium to be effective for 13 of 21 depressed patients. He concludes that there is convincing, although not conclusive, evidence for an antidepressant effect of lithium and that only by identifying the subgroup of patients for whom it is effective can the continuing uncertainty surrounding lithium's role in affective disorder be resolved. He also calls for a reevaluation of the relationship between mania and depression."} {"id": "PMID:1267034", "title": "A review of major implications of the O'Connor v. Donaldson decision.", "content": "Although the Supreme Court's decision in O'Connor v. Donaldson is narrow from the legal perspective, it will have wide clinical applications for psychiatry if it reflects a trend in future court decisions. The author assesses the impact of this decision on the mental health profession in terms of the issue of dangerousness as grounds for involuntary commitment for psychiatric treatment, the principle of least restrictive alternative to hospitalization, the question of adequacy of treatment in light of the absence of nationally defined standards, and the personal liability of physicians for their professional actions.", "contents": "A review of major implications of the O'Connor v. Donaldson decision. Although the Supreme Court's decision in O'Connor v. Donaldson is narrow from the legal perspective, it will have wide clinical applications for psychiatry if it reflects a trend in future court decisions. The author assesses the impact of this decision on the mental health profession in terms of the issue of dangerousness as grounds for involuntary commitment for psychiatric treatment, the principle of least restrictive alternative to hospitalization, the question of adequacy of treatment in light of the absence of nationally defined standards, and the personal liability of physicians for their professional actions."} {"id": "PMID:1267035", "title": "Marijuana effects on simulated flying ability.", "content": "The authors studied the effects of marijuana intoxication on the ability of 10 certified airplane pilots to operate a flight simulator. They used a randomized double-blind crossover design to compare the effect of active versus placebo marijuana. They found that all 10 pilots showed a significant decrease in measurements of flying performance 30 minutes after smoking active marijuana. For a group of 6 pilots tested sequentially for 6 hours, a nonsignificant decrease in flying performance continued for 2 hours after smoking the active drug. The authors conclude that the effects of marijuana on flying performance may represent a sensitive indicator of the drug's psychomotor effects.", "contents": "Marijuana effects on simulated flying ability. The authors studied the effects of marijuana intoxication on the ability of 10 certified airplane pilots to operate a flight simulator. They used a randomized double-blind crossover design to compare the effect of active versus placebo marijuana. They found that all 10 pilots showed a significant decrease in measurements of flying performance 30 minutes after smoking active marijuana. For a group of 6 pilots tested sequentially for 6 hours, a nonsignificant decrease in flying performance continued for 2 hours after smoking the active drug. The authors conclude that the effects of marijuana on flying performance may represent a sensitive indicator of the drug's psychomotor effects."} {"id": "PMID:1267036", "title": "The family in exile: Cuban expatriates in the United States.", "content": "For the nearly one million Cuban exiles in this country, the ordeal of expatriation has meant anguish and uprootedness, challenge and accomplishment. Several factors account for the comparatively successful aspects of their struggle: relatively high occupational and educational levels, formation of vigorous communities that permit the maintenance of a positive ethnic consciousness and the creation of strong social ties, and effectively organized reception by the United States. Expatriation is always traumatic and produces \"casualties,\" but mastery of the struggles it involves can lead to personal growth and expanded horizons. The Cuban expatriate experience shows that the influx of large numbers of refugees can be a creative and enriching process for both the host country and the individual refugee.", "contents": "The family in exile: Cuban expatriates in the United States. For the nearly one million Cuban exiles in this country, the ordeal of expatriation has meant anguish and uprootedness, challenge and accomplishment. Several factors account for the comparatively successful aspects of their struggle: relatively high occupational and educational levels, formation of vigorous communities that permit the maintenance of a positive ethnic consciousness and the creation of strong social ties, and effectively organized reception by the United States. Expatriation is always traumatic and produces \"casualties,\" but mastery of the struggles it involves can lead to personal growth and expanded horizons. The Cuban expatriate experience shows that the influx of large numbers of refugees can be a creative and enriching process for both the host country and the individual refugee."} {"id": "PMID:1267037", "title": "Pseudohomosexuality in feminist students.", "content": "The author describes the influence of the feminist movement on the intellectual, social, and sexual behavior of feminist college students. The complex interrelationship between sexual political ideology and actual sexual behavior creates confusion and anxiety for some vulnerable students in their attempts to evolve a satisfactory sexual identity. A series of vignettes illustrates the struggle of such students, who initially expressed concern over actual or potential lesbianism and its connection to the movement, to resolve their conflicts concerning feminism and sexual preference.", "contents": "Pseudohomosexuality in feminist students. The author describes the influence of the feminist movement on the intellectual, social, and sexual behavior of feminist college students. The complex interrelationship between sexual political ideology and actual sexual behavior creates confusion and anxiety for some vulnerable students in their attempts to evolve a satisfactory sexual identity. A series of vignettes illustrates the struggle of such students, who initially expressed concern over actual or potential lesbianism and its connection to the movement, to resolve their conflicts concerning feminism and sexual preference."} {"id": "PMID:1267038", "title": "It is always the woman who is raped.", "content": "Rape is described as an act of power that is sanctioned by literature, myth, and culture. Rape is a dire experience for women because it implies total loss of self--the woman is a function, not a person. The victim experiences total emptiness and isolation from self and society. The author believes that an effective \"treatment\" for the rape victim is community. Women asserting themselves by speaking out about their experience validate themselves as persons.", "contents": "It is always the woman who is raped. Rape is described as an act of power that is sanctioned by literature, myth, and culture. Rape is a dire experience for women because it implies total loss of self--the woman is a function, not a person. The victim experiences total emptiness and isolation from self and society. The author believes that an effective \"treatment\" for the rape victim is community. Women asserting themselves by speaking out about their experience validate themselves as persons."} {"id": "PMID:1267039", "title": "The rape victim: psychodynamic considerations.", "content": "Rape challenges a woman's ability to maintain her defenses and thus arouses feelings of guilt, anxiety, and inadequacy. Women's individual responses are determined by life stage considerations as well as their defensive structures: concerns about separation-individuation may be aroused in the young woman; a divorced or separated woman may find her credibility questioned; older women's fears of sexual inadequacy may be compounded. In counseling, the victim's previous adjustment should be assessed, she should be given support and reassurance, and specific considerations related to her life circumstances should be acknowledged and dealt with.", "contents": "The rape victim: psychodynamic considerations. Rape challenges a woman's ability to maintain her defenses and thus arouses feelings of guilt, anxiety, and inadequacy. Women's individual responses are determined by life stage considerations as well as their defensive structures: concerns about separation-individuation may be aroused in the young woman; a divorced or separated woman may find her credibility questioned; older women's fears of sexual inadequacy may be compounded. In counseling, the victim's previous adjustment should be assessed, she should be given support and reassurance, and specific considerations related to her life circumstances should be acknowledged and dealt with."} {"id": "PMID:1267040", "title": "Coping behavior of the rape victim.", "content": "The coping behavior of rape victims can be analyzed in three distinct phases--the threat of attack, the attack itself, and the period immediately thereafter. The authors analyzed the reported coping behavior of 92 women diagnosed as having rape trauma. Most of the women used verbal, physical, or cognitive strategies when threatened, although 34 were physically or psychologically paralyzed. The actual rape prompted coping behaviors in all but 1 victim. Escaping the situation or the assailant is the primary task immediately after the attack. In counseling the rape victim, it is important to understand her individual style of coping, to be supportive of it, and to suggest alternatives for future stressful situations.", "contents": "Coping behavior of the rape victim. The coping behavior of rape victims can be analyzed in three distinct phases--the threat of attack, the attack itself, and the period immediately thereafter. The authors analyzed the reported coping behavior of 92 women diagnosed as having rape trauma. Most of the women used verbal, physical, or cognitive strategies when threatened, although 34 were physically or psychologically paralyzed. The actual rape prompted coping behaviors in all but 1 victim. Escaping the situation or the assailant is the primary task immediately after the attack. In counseling the rape victim, it is important to understand her individual style of coping, to be supportive of it, and to suggest alternatives for future stressful situations."} {"id": "PMID:1267041", "title": "Development of a medical center rape crisis intervention program.", "content": "The Rape Crisis Intervention Program at Beth Israel Hospital utilizes volunteer multidisciplinary counseling teams drawn from psychiatry, social work, psychology, and nursing staffs. The premise of the program is that early crisis intervention can prevent later development of psychological disturbances in later development of psychological disturbances in victims. Counselors accompany victims throughout emergency room procedures: follow-up begins 48 hours after the initial contact and continues at regular intervals for at least a year. The authors discuss the problems of implementation, which include staff resistance, finding questions, and varying levels of counseling sophistication, and describe how these difficulties have been handled in their program. They note that this program is becoming a resource center for the community.", "contents": "Development of a medical center rape crisis intervention program. The Rape Crisis Intervention Program at Beth Israel Hospital utilizes volunteer multidisciplinary counseling teams drawn from psychiatry, social work, psychology, and nursing staffs. The premise of the program is that early crisis intervention can prevent later development of psychological disturbances in later development of psychological disturbances in victims. Counselors accompany victims throughout emergency room procedures: follow-up begins 48 hours after the initial contact and continues at regular intervals for at least a year. The authors discuss the problems of implementation, which include staff resistance, finding questions, and varying levels of counseling sophistication, and describe how these difficulties have been handled in their program. They note that this program is becoming a resource center for the community."} {"id": "PMID:1267042", "title": "Assaults on psychiatrists by patients.", "content": "The authors describe the results of a survey of 115 psychiatrists regarding assaults by patients. Forty-eight psychiatrists stated that they had been assaulted; a total of 68 assaults was reported. Psychiatrists were most often assaulted in the early stages of their career or while they were working in high-risk settings such as prisons or emergency rooms. Many reported retrospectively that they might have had a role in provoking the assault and that they could have anticipated it. The authors believe that psychiatrists avoid dealing with the issue of violence by patients for a variety of reasons, and they recommend that clinicians learn techniques for managing potentially assaultive patients.", "contents": "Assaults on psychiatrists by patients. The authors describe the results of a survey of 115 psychiatrists regarding assaults by patients. Forty-eight psychiatrists stated that they had been assaulted; a total of 68 assaults was reported. Psychiatrists were most often assaulted in the early stages of their career or while they were working in high-risk settings such as prisons or emergency rooms. Many reported retrospectively that they might have had a role in provoking the assault and that they could have anticipated it. The authors believe that psychiatrists avoid dealing with the issue of violence by patients for a variety of reasons, and they recommend that clinicians learn techniques for managing potentially assaultive patients."} {"id": "PMID:1267043", "title": "Assault on the therapist.", "content": "The authors conducted a questionnaire survey among psychotherapists in psychiatry, psychology and social work to determine how many patients posed a threat to others or to the therapist and how many actually assaulted the therapist. They found that 9.2% of all patients seen by 101 therapists in one year presented a threat to others, 1.9% posed a physical threat to the therapist, and .63% actually assaulted the therapist. The authors conclude that attacks on a therapist are infrequent but almost inevitable and suggest the development of techniques for coping with assaultive patients that therapists can use in crisis situations.", "contents": "Assault on the therapist. The authors conducted a questionnaire survey among psychotherapists in psychiatry, psychology and social work to determine how many patients posed a threat to others or to the therapist and how many actually assaulted the therapist. They found that 9.2% of all patients seen by 101 therapists in one year presented a threat to others, 1.9% posed a physical threat to the therapist, and .63% actually assaulted the therapist. The authors conclude that attacks on a therapist are infrequent but almost inevitable and suggest the development of techniques for coping with assaultive patients that therapists can use in crisis situations."} {"id": "PMID:1267044", "title": "Nursing aides and patient violence.", "content": "The authors studied the incidence of violence in a psychiatric unit organized as a therapeutic community whose nursing staff was composed entirely of women in comparison with another unit staffed according to the traditional male and female nursing pattern. The unit staffed by women had no incidents of other-directed violence in the one-year period of the study, but the traditionally staffed unit had 13 violent incidents initiated by 5 patients. The authors state that the expectation of violence among psychiatric patients and the consequent use of male nursing aides to control violence may represent a self-fulfilling prophecy.", "contents": "Nursing aides and patient violence. The authors studied the incidence of violence in a psychiatric unit organized as a therapeutic community whose nursing staff was composed entirely of women in comparison with another unit staffed according to the traditional male and female nursing pattern. The unit staffed by women had no incidents of other-directed violence in the one-year period of the study, but the traditionally staffed unit had 13 violent incidents initiated by 5 patients. The authors state that the expectation of violence among psychiatric patients and the consequent use of male nursing aides to control violence may represent a self-fulfilling prophecy."} {"id": "PMID:1267045", "title": "A violence clinic: three years' experience.", "content": "The authors describe a clinical facility established for the neuropsychiatric treatment of individuals with a variety of psychopathological disorders where the common management problem is one of aggressive behavior. The authors present case vignettes to illustrate the clinic's consultation with mental health workers about the management of violent patients, countertransference problems, ward problems, the role of organic factors, medication, and prediction of violence. They urge that the subject of violence be included in the psychiatrist's training.", "contents": "A violence clinic: three years' experience. The authors describe a clinical facility established for the neuropsychiatric treatment of individuals with a variety of psychopathological disorders where the common management problem is one of aggressive behavior. The authors present case vignettes to illustrate the clinic's consultation with mental health workers about the management of violent patients, countertransference problems, ward problems, the role of organic factors, medication, and prediction of violence. They urge that the subject of violence be included in the psychiatrist's training."} {"id": "PMID:1267046", "title": "Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients.", "content": "Platelet monoamine oxidase (MAO) activity was significantly lower than control values in a subgroup of 16 schizophrenic patients (most of whom were paranoid) characterized by the presence of auditory hallucinations and delusions. Platelet MAO activity was not reduced in 16 other schizophrenic patients without auditory hallucinations. This finding suggests that reduced platelet MAO activity is not found in all schizophrenic patients but tends to occur in a clinically identifiable subgroup.", "contents": "Reduced platelet monoamine oxidase activity in a subgroup of schizophrenic patients. Platelet monoamine oxidase (MAO) activity was significantly lower than control values in a subgroup of 16 schizophrenic patients (most of whom were paranoid) characterized by the presence of auditory hallucinations and delusions. Platelet MAO activity was not reduced in 16 other schizophrenic patients without auditory hallucinations. This finding suggests that reduced platelet MAO activity is not found in all schizophrenic patients but tends to occur in a clinically identifiable subgroup."} {"id": "PMID:1267047", "title": "The 24-hour lithium level as a prognosticator of dosage requirements: a 2-year follow-up study.", "content": "The authors have previously described a technique whereby individual lithium dosage requirements can be predicted from 24-hour blood samples. Further experience over a 2-year period has shown the predictions to be reproducible over time. A micromethod for lithium determination is described, as are several cases in which aberrant results were found to indicate inadequate laboratory techniques or patients' failure to take medication. Because the technique reveals immediately those patients at the extremes of dosage ranges, toxicity and the need for frequent sampling can be avoided.", "contents": "The 24-hour lithium level as a prognosticator of dosage requirements: a 2-year follow-up study. The authors have previously described a technique whereby individual lithium dosage requirements can be predicted from 24-hour blood samples. Further experience over a 2-year period has shown the predictions to be reproducible over time. A micromethod for lithium determination is described, as are several cases in which aberrant results were found to indicate inadequate laboratory techniques or patients' failure to take medication. Because the technique reveals immediately those patients at the extremes of dosage ranges, toxicity and the need for frequent sampling can be avoided."} {"id": "PMID:1267048", "title": "Extrapyramidal side effects in lithium maintenance therapy.", "content": "The authors neurologically examined 36 patients who had been maintained on lithium therapy for periods ranging from 6 months to 7 years to determine the presence of parkinson-like side effects. Only a few patients demonstrated rigidity, including cogweel rigidity, and this was at a low level of severity. These results do not support the previously reported frequent occurrence of cogwheel rigidity in patients on lithium maintenance.", "contents": "Extrapyramidal side effects in lithium maintenance therapy. The authors neurologically examined 36 patients who had been maintained on lithium therapy for periods ranging from 6 months to 7 years to determine the presence of parkinson-like side effects. Only a few patients demonstrated rigidity, including cogweel rigidity, and this was at a low level of severity. These results do not support the previously reported frequent occurrence of cogwheel rigidity in patients on lithium maintenance."} {"id": "PMID:1267049", "title": "Catatonia, gastric hyperacidity, and fatal aspiration: a preventable syndrome.", "content": "Sudden death from aspiration pneumonitis during acute catatonia is a generally recognized but poorly understood occurrence. The author describes a case in which a schizophrenic patient died following aspiration of gastric contents. In view of findings that suggest that the acidity of gastric contents is related to morbidity following aspiration, he recommends that liquid antacid medication be given routinely to catatonic patients.", "contents": "Catatonia, gastric hyperacidity, and fatal aspiration: a preventable syndrome. Sudden death from aspiration pneumonitis during acute catatonia is a generally recognized but poorly understood occurrence. The author describes a case in which a schizophrenic patient died following aspiration of gastric contents. In view of findings that suggest that the acidity of gastric contents is related to morbidity following aspiration, he recommends that liquid antacid medication be given routinely to catatonic patients."} {"id": "PMID:1267051", "title": "The life of psychiatry.", "content": "Focusing on the definition, scope, and role of psychiatry today, the author discusses whether psychiatry is primarily medical, whether it is overstepping its boundaries in attempting to treat problems of living, and whether it is too involved with social questions. On the basis of an examination of the current scientific base of psychiatry, he predicts that psychiatry will continue to grow in size and diversity, that it will refocus substantially on biological issues, that it will become more humble about what it can do with regard to social problems, and that it will continue to yield new therapeutic measures and techniques.", "contents": "The life of psychiatry. Focusing on the definition, scope, and role of psychiatry today, the author discusses whether psychiatry is primarily medical, whether it is overstepping its boundaries in attempting to treat problems of living, and whether it is too involved with social questions. On the basis of an examination of the current scientific base of psychiatry, he predicts that psychiatry will continue to grow in size and diversity, that it will refocus substantially on biological issues, that it will become more humble about what it can do with regard to social problems, and that it will continue to yield new therapeutic measures and techniques."} {"id": "PMID:1267052", "title": "The case for involuntary hospitalization of the mentally ill.", "content": "The author examines three points of view on the question of society's right to involuntarily hospitalize a mentally ill individual. The \"abolitionists\" oppose involuntary hospitalization entirely; the medical model psychiatrists support the need for commitment under certain circumstances and so do the civil liberties lawyers, but by different standards. The author believes that with the current overreliance on the dangerousness standard, we are witnessing a pendular swing in which the rights of the mentally ill to be treated and protected are being set aside in the rush to give them their freedom. He favors a return to the use of medical criteria by psychiatrists, albeit with constructive legal safeguards.", "contents": "The case for involuntary hospitalization of the mentally ill. The author examines three points of view on the question of society's right to involuntarily hospitalize a mentally ill individual. The \"abolitionists\" oppose involuntary hospitalization entirely; the medical model psychiatrists support the need for commitment under certain circumstances and so do the civil liberties lawyers, but by different standards. The author believes that with the current overreliance on the dangerousness standard, we are witnessing a pendular swing in which the rights of the mentally ill to be treated and protected are being set aside in the rush to give them their freedom. He favors a return to the use of medical criteria by psychiatrists, albeit with constructive legal safeguards."} {"id": "PMID:1267053", "title": "Drug and psychotherapy interactions in depression.", "content": "The authors conducted a series of multiple regression analyses of data from depressed patients. They found that 8 factors consistently predicted treatment response: a lower initial level of distress, imipramine treatment, a positive attitude toward group psychotherapy, and a good employment history predicted lower posttreatment distress levels; estrogen maintenance treatment was related to better response to diazepam, and a low level of intelligence predicted better response to both diazepam and imipramine; and a low initial level of interpersonal sensitivity and a significant other's having an unfavorable attitude toward psychiatric treatment were associated with better response to group psychotherapy.", "contents": "Drug and psychotherapy interactions in depression. The authors conducted a series of multiple regression analyses of data from depressed patients. They found that 8 factors consistently predicted treatment response: a lower initial level of distress, imipramine treatment, a positive attitude toward group psychotherapy, and a good employment history predicted lower posttreatment distress levels; estrogen maintenance treatment was related to better response to diazepam, and a low level of intelligence predicted better response to both diazepam and imipramine; and a low initial level of interpersonal sensitivity and a significant other's having an unfavorable attitude toward psychiatric treatment were associated with better response to group psychotherapy."} {"id": "PMID:1267054", "title": "Short versus long hospitalization: a prospective controlled study. V. One-year follow-up results for nonschizophrenie patients.", "content": "The authors studied the effect of long-term versus short-term hospitalization on a group of 74 patients with the diagnoses of affective disorder, neurosis and personality disorder, and hysterical personality one year after their admission to the hospital. Although they had found in an earlier study that short-term patients seemed to integrate more rapidly in the hospital, the results reported in this study showed no statistically reliable differences between the long-term and short-term groups. In contrast to the author's results for schizophrenic patients, their findings for nonschizophrenic patients do not support extended hospitalization.", "contents": "Short versus long hospitalization: a prospective controlled study. V. One-year follow-up results for nonschizophrenie patients. The authors studied the effect of long-term versus short-term hospitalization on a group of 74 patients with the diagnoses of affective disorder, neurosis and personality disorder, and hysterical personality one year after their admission to the hospital. Although they had found in an earlier study that short-term patients seemed to integrate more rapidly in the hospital, the results reported in this study showed no statistically reliable differences between the long-term and short-term groups. In contrast to the author's results for schizophrenic patients, their findings for nonschizophrenic patients do not support extended hospitalization."} {"id": "PMID:1267055", "title": "Psychosis, thought disorder, and regression.", "content": "Focusing on the definition, scope, and role of psychiatry today, the author discusses whether psychiatry is primarily medical, whether it is overstepping its boundaries in attempting to treat problems of living, and whether it is too involved with social questions. On the basis of an examination of the current scientific base of psychiatry, he predicts that psychiatry will continue to grow in size and diversity, that it will refocus substantially on biological issues, that it will become more humble about what it can do with regard to social problems, and that it will continue to yield new therapeutic measures and techniques.", "contents": "Psychosis, thought disorder, and regression. Focusing on the definition, scope, and role of psychiatry today, the author discusses whether psychiatry is primarily medical, whether it is overstepping its boundaries in attempting to treat problems of living, and whether it is too involved with social questions. On the basis of an examination of the current scientific base of psychiatry, he predicts that psychiatry will continue to grow in size and diversity, that it will refocus substantially on biological issues, that it will become more humble about what it can do with regard to social problems, and that it will continue to yield new therapeutic measures and techniques."} {"id": "PMID:1267056", "title": "Behavioral changes following surgery for obesity.", "content": "The authors interviewed 69 subjects who had had jejuno-ileal bypass surgery for obesity to determine the relationship between weight loss and eating behavior after surgery. All patients had been extremely overweight; at an average of 37 months after surgery, their mean weight was reduced by 39%. There were four significant postoperative changes: voluntary restriction of food intake, \"normalization\" of eating patterns, resistance to eating during intense emotion, and far less dysphoria during postsurgical weight loss than during previous weight loss efforts. The authors therefore suggest that factors other than impaired intestinal absorption may account for some portion of postsurgical weight loss.", "contents": "Behavioral changes following surgery for obesity. The authors interviewed 69 subjects who had had jejuno-ileal bypass surgery for obesity to determine the relationship between weight loss and eating behavior after surgery. All patients had been extremely overweight; at an average of 37 months after surgery, their mean weight was reduced by 39%. There were four significant postoperative changes: voluntary restriction of food intake, \"normalization\" of eating patterns, resistance to eating during intense emotion, and far less dysphoria during postsurgical weight loss than during previous weight loss efforts. The authors therefore suggest that factors other than impaired intestinal absorption may account for some portion of postsurgical weight loss."} {"id": "PMID:1267057", "title": "The significance of childhood neurosis for adult mental health: a follow-up study.", "content": "The author compared the mental health of 42 young adults who had suffered from a neurosis in childhood with that of 20 control subjects. Various aspects of functioning were clinically assessed using the Current and Past Psychopathology Scales and the Health-Sickness Rating Scale. More than 75% of the former patients were at least mildly ill at follow-up, compared with only 15% of the control group. Intergroup differences in diagnoses and symptoms are described. The findings establish the fact that neurotic children require much more effective treatment than they have traditionally received in order to attain a good prognosis for adult mental health.", "contents": "The significance of childhood neurosis for adult mental health: a follow-up study. The author compared the mental health of 42 young adults who had suffered from a neurosis in childhood with that of 20 control subjects. Various aspects of functioning were clinically assessed using the Current and Past Psychopathology Scales and the Health-Sickness Rating Scale. More than 75% of the former patients were at least mildly ill at follow-up, compared with only 15% of the control group. Intergroup differences in diagnoses and symptoms are described. The findings establish the fact that neurotic children require much more effective treatment than they have traditionally received in order to attain a good prognosis for adult mental health."} {"id": "PMID:1267058", "title": "Evolution of behavior disorders into adolescence.", "content": "The New York longitudinal study has followed the development of 136 subjects from infancy into adolescence. The authors report the distribution of diagnoses and outcome of 43 children who developed behavior problems before the adolescent period and the characteristics of 5 new cases diagnosed in adolescence and discuss issues of prediction. The analysis of the longitudinal data for subjects with and without behavior disorders permits discussion of two of the general issues in the literature: the significance of adolescent turmoil and the distinctness of adolescence as a developmental stage.", "contents": "Evolution of behavior disorders into adolescence. The New York longitudinal study has followed the development of 136 subjects from infancy into adolescence. The authors report the distribution of diagnoses and outcome of 43 children who developed behavior problems before the adolescent period and the characteristics of 5 new cases diagnosed in adolescence and discuss issues of prediction. The analysis of the longitudinal data for subjects with and without behavior disorders permits discussion of two of the general issues in the literature: the significance of adolescent turmoil and the distinctness of adolescence as a developmental stage."} {"id": "PMID:1267059", "title": "The role of neurosis in phylogenetic adaptation, with particular reference to early man.", "content": "The author hypothesizes that neurosis results from maladaptation and leads to further maladaptation, thus creating a vicious cycle that can be viewed as having played a significant role in human evolution. Individuals who were less successful in the struggle for survival during prehistory would have been more likely to become neurotic, a maladaptation that would magnify existing genetically transmitted differences in their viability and affect both the choice of a mate and the viability of their offspring. This process would have accelerated human evolution by favoring the most viable. The author relates this theory to his concepts of assortative mating and to other theories of the role of neurosis.", "contents": "The role of neurosis in phylogenetic adaptation, with particular reference to early man. The author hypothesizes that neurosis results from maladaptation and leads to further maladaptation, thus creating a vicious cycle that can be viewed as having played a significant role in human evolution. Individuals who were less successful in the struggle for survival during prehistory would have been more likely to become neurotic, a maladaptation that would magnify existing genetically transmitted differences in their viability and affect both the choice of a mate and the viability of their offspring. This process would have accelerated human evolution by favoring the most viable. The author relates this theory to his concepts of assortative mating and to other theories of the role of neurosis."} {"id": "PMID:1267060", "title": "Principles of the new sex therapy.", "content": "The authors review the development of their rapid treatment dual-sex therapy for sexual dysfunction. The basic tenets of the new sex therapy include 1) sound knowledge of physiology, endocrinology, and metabolic function, 2) institution of psychotherapy only when organic factors have been identified or ruled out, 3) treatment of the couple as a unit by dual-sex therapy teams, 4) a short-term intensive program, and 5) education in techniques of verbal and nonverbal communication. Since its inception in 1958, the new therapy has been adopted, modified, and examined by clinicians and researchers all over the world. The authors suggest that professionals interested in effective treatment for sexual dysfunction should improve techniques, train personnel, and encourage sound research.", "contents": "Principles of the new sex therapy. The authors review the development of their rapid treatment dual-sex therapy for sexual dysfunction. The basic tenets of the new sex therapy include 1) sound knowledge of physiology, endocrinology, and metabolic function, 2) institution of psychotherapy only when organic factors have been identified or ruled out, 3) treatment of the couple as a unit by dual-sex therapy teams, 4) a short-term intensive program, and 5) education in techniques of verbal and nonverbal communication. Since its inception in 1958, the new therapy has been adopted, modified, and examined by clinicians and researchers all over the world. The authors suggest that professionals interested in effective treatment for sexual dysfunction should improve techniques, train personnel, and encourage sound research."} {"id": "PMID:1267061", "title": "The role of sex therapy in marial therapy.", "content": "Marital and sex therapy are clinically interrelated in most cases because they deal with different symptoms of overlapping aspects of the couple's total relationship. The connection between marital discord and sexual dysfunction determines the emphasis and course of treatment. For example, sex therapy is the immediate treatment of choice when sexual dysfunction produces secondary marital discord but not when severe discord precludes the possibility of good sexual functioning. The author presents case reports to illustrate the relationship of remote and immediate causes of marital and sexual problems and to emphasize the value of a multimodality approach to treatment.", "contents": "The role of sex therapy in marial therapy. Marital and sex therapy are clinically interrelated in most cases because they deal with different symptoms of overlapping aspects of the couple's total relationship. The connection between marital discord and sexual dysfunction determines the emphasis and course of treatment. For example, sex therapy is the immediate treatment of choice when sexual dysfunction produces secondary marital discord but not when severe discord precludes the possibility of good sexual functioning. The author presents case reports to illustrate the relationship of remote and immediate causes of marital and sexual problems and to emphasize the value of a multimodality approach to treatment."} {"id": "PMID:1267062", "title": "Profiles of couples seeking sex therapy and marital therapy.", "content": "Assessment of 29 couples seeking marital therapy and 25 seeking sexual therapy at the same institution permitted the delineation of two distinct profiles. Although the two groups were similar in the degree of their sexual and marital difficulties and in demographic characteristics, the relationships of the sex therapy couples were generally characterized by satisfaction and affection, whereas those of the marital therapy couples were often antagonistic. In addition, the sex therapy couples tended to be less conservative and more thoughtful in their approach to life and their problems.", "contents": "Profiles of couples seeking sex therapy and marital therapy. Assessment of 29 couples seeking marital therapy and 25 seeking sexual therapy at the same institution permitted the delineation of two distinct profiles. Although the two groups were similar in the degree of their sexual and marital difficulties and in demographic characteristics, the relationships of the sex therapy couples were generally characterized by satisfaction and affection, whereas those of the marital therapy couples were often antagonistic. In addition, the sex therapy couples tended to be less conservative and more thoughtful in their approach to life and their problems."} {"id": "PMID:1267063", "title": "Relationship between dosage and response to lithium prophylaxis in recurrent depression.", "content": "The authors analyzed the results of a multihospital collaborative study on the effectiveness of lithium prophylaxis in recurrent depression in terms of dosage and found that serum lithium levels between 0.5 and 0.7 mEq/liter and doses below 1000 mg/day were relatively ineffective in preventing recurrences. Serum lithium levels between 0.8 and 1.0 mEq/liter and doses above 1000 mg/day were associated with a relatively low failure rate. The authors discuss the relevance of these findings to current prescription guidelines for lithium carbonate.", "contents": "Relationship between dosage and response to lithium prophylaxis in recurrent depression. The authors analyzed the results of a multihospital collaborative study on the effectiveness of lithium prophylaxis in recurrent depression in terms of dosage and found that serum lithium levels between 0.5 and 0.7 mEq/liter and doses below 1000 mg/day were relatively ineffective in preventing recurrences. Serum lithium levels between 0.8 and 1.0 mEq/liter and doses above 1000 mg/day were associated with a relatively low failure rate. The authors discuss the relevance of these findings to current prescription guidelines for lithium carbonate."} {"id": "PMID:1267064", "title": "Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage.", "content": "The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule.", "contents": "Pavor nocturnus: a complication of single daily tricyclic or neuroleptic dosage. The author tested the hypothesis that a single bedtime dosage schedule of tricyclic or neuroleptic medication produces increased frequency of night terrors by administering a questionnaire to 30 medical patients who were not receiving such medications and 100 psychiatric patients on either multiple- or single-dosage schedules. Psychiatric patients on multiple-dosage schedules reported no more frightening dreams than the medical patients, whereas almost three-fourths of those receiving single bedtime doses had frightening dreams, a significant difference from the medical sample. This preliminary report is presented to call attention to the possible undesirable effects of a single dose schedule."} {"id": "PMID:1267066", "title": "Is dying being worked to death?", "content": "In recent years there has been a dramatic increase in the number of books and articles on death and dying. The ambivalence of some writers regarding the value of this proliferation of papers led the author to review and evaluate this literature; he found seven overlapping categories of death-related literature that were of both theoretical and practical value. He briefly explores possible reasons for the rise in this subject's popularity.", "contents": "Is dying being worked to death? In recent years there has been a dramatic increase in the number of books and articles on death and dying. The ambivalence of some writers regarding the value of this proliferation of papers led the author to review and evaluate this literature; he found seven overlapping categories of death-related literature that were of both theoretical and practical value. He briefly explores possible reasons for the rise in this subject's popularity."} {"id": "PMID:1267067", "title": "Computerized tomography in patients with tardive dyskinesia.", "content": "The author reviews the results of computerized tomography performed on eight patients with tardive dyskinesia to determine whether there was permanent structural damage. No significant abnormalities were found. Although it may not be useful in routine workups, this new noninvasive technique might be helpful in differential diagnosis, and its increasing sophistication may suggest further research on tardive dyskinesia.", "contents": "Computerized tomography in patients with tardive dyskinesia. The author reviews the results of computerized tomography performed on eight patients with tardive dyskinesia to determine whether there was permanent structural damage. No significant abnormalities were found. Although it may not be useful in routine workups, this new noninvasive technique might be helpful in differential diagnosis, and its increasing sophistication may suggest further research on tardive dyskinesia."} {"id": "PMID:1267068", "title": "Hypothalamic tumor presenting as anorexia nervosa.", "content": "The authors describe a patient with symptoms of anorexia nervosa who was initially treated on a psychiatric ward but was later found to have a hypothalamic tumor. They recommend repeated neurological and endocrine evaluations for patients with anorexia nervosa who are unresponsive or only partially responsive to psychiatric treatment. Initially negative medical evaluations, obvious psychopathology, and even some response to treatment may all prove insufficient to rule out organic disease.", "contents": "Hypothalamic tumor presenting as anorexia nervosa. The authors describe a patient with symptoms of anorexia nervosa who was initially treated on a psychiatric ward but was later found to have a hypothalamic tumor. They recommend repeated neurological and endocrine evaluations for patients with anorexia nervosa who are unresponsive or only partially responsive to psychiatric treatment. Initially negative medical evaluations, obvious psychopathology, and even some response to treatment may all prove insufficient to rule out organic disease."} {"id": "PMID:1267078", "title": "Current regulatory status of foods for special dietary uses.", "content": "The Food and Drug Administration has redefined foods for \"special dietary use\". Such foods must now: (1) Supply a special dietary need that exists by reason of a physical or physiological condition, such as convalescence, a pregnancy, lactation, or by reason of a specific disease or disorder; (2) Supply a vitamin, mineral, or other dietary property to supplement diet by increasing total dietary intake; (3) Meet a special nutritional need as the sole item of the diet. The stricter definition of this category of food means that the conventional foods with added nutrients or food for which nutritional claims are made or nutritional information provided will no longer be considered as foods for special dietary uses, although they must conform to standard nutritional labeling requirements. The new regulation establishes a clearly delineated position within which the consumer, industry, and FDA can deal with special dietary foods without the past confusion as to what belonged in this category.", "contents": "Current regulatory status of foods for special dietary uses. The Food and Drug Administration has redefined foods for \"special dietary use\". Such foods must now: (1) Supply a special dietary need that exists by reason of a physical or physiological condition, such as convalescence, a pregnancy, lactation, or by reason of a specific disease or disorder; (2) Supply a vitamin, mineral, or other dietary property to supplement diet by increasing total dietary intake; (3) Meet a special nutritional need as the sole item of the diet. The stricter definition of this category of food means that the conventional foods with added nutrients or food for which nutritional claims are made or nutritional information provided will no longer be considered as foods for special dietary uses, although they must conform to standard nutritional labeling requirements. The new regulation establishes a clearly delineated position within which the consumer, industry, and FDA can deal with special dietary foods without the past confusion as to what belonged in this category."} {"id": "PMID:1267080", "title": "Measuring response to a cancer information telephone facility: Can-Dial.", "content": "In an attempt to meet the need for increasing public knowledge about cancer, a system providing free information by telephone has been developed. The system is comprised of 36 pre-recorded taped lectures containing information about various aspects of cancer. Interested individuals call a toll-free number, indicate a topic of interest, and listen to the pre-recorded lecture over the phone. An operator handles incoming calls and obtains information from callers used in evaluating the program. During the first year of operation, over 30,000 calls were processed. Topics most frequently requested included those concerning smoking, breast and cervical cancer, and general information. Female response exceeded male response in all age categories. Older people responded less frequently than younger. Urban utilization greatly exceeded suburban and rural utilization. Considerable fluctuation in response related to promotional activities was found. Printed advertisements elicited far greater response than radio and television. Promotional efforts in an experimental group of low-utilizing townships greatly increased utilization while no change was observed in a control group.", "contents": "Measuring response to a cancer information telephone facility: Can-Dial. In an attempt to meet the need for increasing public knowledge about cancer, a system providing free information by telephone has been developed. The system is comprised of 36 pre-recorded taped lectures containing information about various aspects of cancer. Interested individuals call a toll-free number, indicate a topic of interest, and listen to the pre-recorded lecture over the phone. An operator handles incoming calls and obtains information from callers used in evaluating the program. During the first year of operation, over 30,000 calls were processed. Topics most frequently requested included those concerning smoking, breast and cervical cancer, and general information. Female response exceeded male response in all age categories. Older people responded less frequently than younger. Urban utilization greatly exceeded suburban and rural utilization. Considerable fluctuation in response related to promotional activities was found. Printed advertisements elicited far greater response than radio and television. Promotional efforts in an experimental group of low-utilizing townships greatly increased utilization while no change was observed in a control group."} {"id": "PMID:1267081", "title": "A facet of the biohazard control program: agent registration, risk assessment and computerization of data.", "content": "An assessment of risk in handling microbial agents at a major biomedical research institute is given. Included also are the risks associated with handling tissue cultures and animals. Two computer programs are described for the storage and retrieval of data on agents, tissue cultures, and animals.", "contents": "A facet of the biohazard control program: agent registration, risk assessment and computerization of data. An assessment of risk in handling microbial agents at a major biomedical research institute is given. Included also are the risks associated with handling tissue cultures and animals. Two computer programs are described for the storage and retrieval of data on agents, tissue cultures, and animals."} {"id": "PMID:1267082", "title": "Sociocultural influences upon preventive health behavior and attitudes towards dentistry.", "content": "One hundred eighty adults who presented for general dental care at an urban dental school clinic were interviewed and given epidemiological screening examinations. The findings presented include a profile of a clinic population with respect to ethnic identity, family income, education, nuclear family structure, and residence. The two major racial groups (black and white) are found to have highly significant differences in their perception of dental services and their experiences with dental disease and treatment. An assessment of dental health status indicates that whites were more likely to have filled teeth, and blacks, decayed or unfilled teeth. This relates to different patterns in seeking recent preventive dental services and a marked disparity in utilization early in life. Fear and anxiety about dental care, degree of orientation towards prevention and differences in exposure to preventive information varied with race. Consumerist orientation is examined in terms of willingness to criticize services, be cared for by auxiliary health workers and accept professional fees. The identification of diversity in perception and values with respect to dental health care is characterized as an element in developing understanding between providers and consumers.", "contents": "Sociocultural influences upon preventive health behavior and attitudes towards dentistry. One hundred eighty adults who presented for general dental care at an urban dental school clinic were interviewed and given epidemiological screening examinations. The findings presented include a profile of a clinic population with respect to ethnic identity, family income, education, nuclear family structure, and residence. The two major racial groups (black and white) are found to have highly significant differences in their perception of dental services and their experiences with dental disease and treatment. An assessment of dental health status indicates that whites were more likely to have filled teeth, and blacks, decayed or unfilled teeth. This relates to different patterns in seeking recent preventive dental services and a marked disparity in utilization early in life. Fear and anxiety about dental care, degree of orientation towards prevention and differences in exposure to preventive information varied with race. Consumerist orientation is examined in terms of willingness to criticize services, be cared for by auxiliary health workers and accept professional fees. The identification of diversity in perception and values with respect to dental health care is characterized as an element in developing understanding between providers and consumers."} {"id": "PMID:1267085", "title": "Lead poisoning among migrant children in New York State.", "content": "Potentially hazardous painted surfaces were found in 40% of 166 dwelling units surveyed in 97 upstate New York migrant labor camps, a figure substantially lower than comparable surveys in upstate New York high risk urban areas. Blood samples obtained from 79 migrant children in 1972 revealed only one child with blood lead level above 40 mug per 100 ml as compared to a 21.6% yield from 5,733 high risk urban area children. A second screening program in 1974 yielded only three children of 190 tested with proven blood lead levels above 40 mug per 100 ml, although seven additional children with possible elevations were lost to follow-up.", "contents": "Lead poisoning among migrant children in New York State. Potentially hazardous painted surfaces were found in 40% of 166 dwelling units surveyed in 97 upstate New York migrant labor camps, a figure substantially lower than comparable surveys in upstate New York high risk urban areas. Blood samples obtained from 79 migrant children in 1972 revealed only one child with blood lead level above 40 mug per 100 ml as compared to a 21.6% yield from 5,733 high risk urban area children. A second screening program in 1974 yielded only three children of 190 tested with proven blood lead levels above 40 mug per 100 ml, although seven additional children with possible elevations were lost to follow-up."} {"id": "PMID:1267086", "title": "The effects of anticipated funding changes on maternal and child health projects: a case study of uncertainty.", "content": "A questionnaire survey of Title V special projects--Maternal and Infant Care (M&I), Comprehensive Care for Children and Youth (C&Y), Neonatal Intensive Care and Children's Dental Care--indicated that the anticipated change from federal project grants to state formula grants caused anxiety among project directors, low morale and high turnover in project staff, difficulty in filling staff positions, and anticipation of service reductions. These effects were much more prevalent and severe in projects which could realistically be expected to suffer budget cuts as a result of the shift in funding method. Despite the widespread anxiety, low morale and adverse effects reported by program directors, there was no reduction in the number of patients served, the scope of services offered, or the number of staff employed.", "contents": "The effects of anticipated funding changes on maternal and child health projects: a case study of uncertainty. A questionnaire survey of Title V special projects--Maternal and Infant Care (M&I), Comprehensive Care for Children and Youth (C&Y), Neonatal Intensive Care and Children's Dental Care--indicated that the anticipated change from federal project grants to state formula grants caused anxiety among project directors, low morale and high turnover in project staff, difficulty in filling staff positions, and anticipation of service reductions. These effects were much more prevalent and severe in projects which could realistically be expected to suffer budget cuts as a result of the shift in funding method. Despite the widespread anxiety, low morale and adverse effects reported by program directors, there was no reduction in the number of patients served, the scope of services offered, or the number of staff employed."} {"id": "PMID:1267087", "title": "The genetic associate: a new health professional.", "content": "Sarah Lawrence College has pioneered a masters program to train Genetic Associates. The Genetic Associate is a new category of allied health professional in clinical genetics. Trained to offer coordinative and supportive care to the patient with potential or actual genetic disease, Genetic Associates are potential providers of unmet health needs in the developing field of human genetics. There are 56 graduates of this program employed in 12 states and one foreign country. This paper describes the curriculum, the students, and a preliminary evaluation of Genetic Associates' performance as members of the health care team.", "contents": "The genetic associate: a new health professional. Sarah Lawrence College has pioneered a masters program to train Genetic Associates. The Genetic Associate is a new category of allied health professional in clinical genetics. Trained to offer coordinative and supportive care to the patient with potential or actual genetic disease, Genetic Associates are potential providers of unmet health needs in the developing field of human genetics. There are 56 graduates of this program employed in 12 states and one foreign country. This paper describes the curriculum, the students, and a preliminary evaluation of Genetic Associates' performance as members of the health care team."} {"id": "PMID:1267091", "title": "Limited surgical excision as the basis of a comprehensive therapy for cancer of the breast.", "content": "A comprehensive program of therapy has evolved with collaborating roles for surgery, pathology, radiotherapy, and chemotherapy. Our experience includes 131 patients with breast cancer treated at the Massachusetts General Hospital since 1956 by limited excision of the cancer. The tumors of 10 patients were noninvasive or sluggishly so; the patients received no further therapy. Because of the invasive character of their tumor, 121 patients received heavy postoperative irradiation. In 12 of these 121, the irradiation has been followed by immediate and prolonged chemotherapy. It is too soon to judge the effect of the chemotherapy, but survival rates of those treated by limited excision and primary irradiation compare favorably with those of patients treated by radical mastectomy.", "contents": "Limited surgical excision as the basis of a comprehensive therapy for cancer of the breast. A comprehensive program of therapy has evolved with collaborating roles for surgery, pathology, radiotherapy, and chemotherapy. Our experience includes 131 patients with breast cancer treated at the Massachusetts General Hospital since 1956 by limited excision of the cancer. The tumors of 10 patients were noninvasive or sluggishly so; the patients received no further therapy. Because of the invasive character of their tumor, 121 patients received heavy postoperative irradiation. In 12 of these 121, the irradiation has been followed by immediate and prolonged chemotherapy. It is too soon to judge the effect of the chemotherapy, but survival rates of those treated by limited excision and primary irradiation compare favorably with those of patients treated by radical mastectomy."} {"id": "PMID:1267093", "title": "Penetrating cardiac trauma. Experience with thirty-four patients in a hospital without cardiopulmonary bypass capability.", "content": "A review of thirty-four consecutive penetrating wounds of the heart is presented. Thirty-one patients were in shock at the time of admission, and fourteen had no obtainable blood pressure and were comatose or moribund. The weapon used, clinical status of the patient on arrival, size of the cardiac wound, and presence of associated injuries affected the mortality rate. Seven of the eight deaths were considered unpreventable due to clinical deterioration by the time of arrival. Clinical recognition of cardiac tamponade is stressed. Early open thoracotomy and closure of the cardiac wound is advocated as the preferred method of treating this injury. No patient was lost due to lack of cardiopulmonary bypass capability.", "contents": "Penetrating cardiac trauma. Experience with thirty-four patients in a hospital without cardiopulmonary bypass capability. A review of thirty-four consecutive penetrating wounds of the heart is presented. Thirty-one patients were in shock at the time of admission, and fourteen had no obtainable blood pressure and were comatose or moribund. The weapon used, clinical status of the patient on arrival, size of the cardiac wound, and presence of associated injuries affected the mortality rate. Seven of the eight deaths were considered unpreventable due to clinical deterioration by the time of arrival. Clinical recognition of cardiac tamponade is stressed. Early open thoracotomy and closure of the cardiac wound is advocated as the preferred method of treating this injury. No patient was lost due to lack of cardiopulmonary bypass capability."} {"id": "PMID:1267094", "title": "Gastric bypass.", "content": "Gastric bypass in the very obese is a technically difficult and tedious procedure done in the attic of the peritoneal cavity. However, with careful attention to pre-, intra-, and postoperative detail, it is reasonably safe, effective, and relatively free from unmanageable complications.", "contents": "Gastric bypass. Gastric bypass in the very obese is a technically difficult and tedious procedure done in the attic of the peritoneal cavity. However, with careful attention to pre-, intra-, and postoperative detail, it is reasonably safe, effective, and relatively free from unmanageable complications."} {"id": "PMID:1267095", "title": "Anterior resection for adenocarcinoma. Lahey Clinic experience from 1963 through 1969.", "content": "The results of anterior resection for adenocarcinoma of the rectum and rectosigmoid are reported with respect to survival rates and complications. Anastomotic recurrence is related to low lying, ulcerated, and less well differentiated tumors that have penetrated the bowel wall. The incidence of recurrent disease at the anastomosis increases with decreases in the margin of resection. Distal margins of at least 6 cm offer significant protection from recurrence. This study shows that anastomotic septic and fistulous complications are related to advanced age, diabetes, anemia, atherosclerotic disease, construction of the anastomosis below the peritoneal reflection, perforated bowel, obstructed bowel, and the use of drains. The determination of those factors that correlate with the development of anastomotic complications can be accomplished with pre- and intraoperative examinations. The role of these factors in operative decision-making and patient management is emphasized.", "contents": "Anterior resection for adenocarcinoma. Lahey Clinic experience from 1963 through 1969. The results of anterior resection for adenocarcinoma of the rectum and rectosigmoid are reported with respect to survival rates and complications. Anastomotic recurrence is related to low lying, ulcerated, and less well differentiated tumors that have penetrated the bowel wall. The incidence of recurrent disease at the anastomosis increases with decreases in the margin of resection. Distal margins of at least 6 cm offer significant protection from recurrence. This study shows that anastomotic septic and fistulous complications are related to advanced age, diabetes, anemia, atherosclerotic disease, construction of the anastomosis below the peritoneal reflection, perforated bowel, obstructed bowel, and the use of drains. The determination of those factors that correlate with the development of anastomotic complications can be accomplished with pre- and intraoperative examinations. The role of these factors in operative decision-making and patient management is emphasized."} {"id": "PMID:1267096", "title": "Acute perforation of the colon associated with chronic corticosteroid therapy.", "content": "Perforation of the colon occurred in thirteen patients receiving corticosteroids for diseases unrelated to the bowel. Treatment averaged 3.5 years. The paucity of symptoms, signs, and laboratory indexes of visceral perforation led to frequent delays in treatment and to incorrect preoperative diagnoses in all but three patients. The perforations were often unusual in location (cecum, hepatic flexure, and multiple points in the transverse and descending colon) and often resulted from single punched-out ulcers in otherwise normal bowel. In seven patients the lesion could not be distinguished from perforated sigmoid diverticulitis, but in two of these patients the ulcerations were found in adjacent diverticula. The evidence strongly suggests that corticosteroids can be responsible for ulceration and perforation of the colon either by direct injury or by interference with normal mechanisms of bowel repair.", "contents": "Acute perforation of the colon associated with chronic corticosteroid therapy. Perforation of the colon occurred in thirteen patients receiving corticosteroids for diseases unrelated to the bowel. Treatment averaged 3.5 years. The paucity of symptoms, signs, and laboratory indexes of visceral perforation led to frequent delays in treatment and to incorrect preoperative diagnoses in all but three patients. The perforations were often unusual in location (cecum, hepatic flexure, and multiple points in the transverse and descending colon) and often resulted from single punched-out ulcers in otherwise normal bowel. In seven patients the lesion could not be distinguished from perforated sigmoid diverticulitis, but in two of these patients the ulcerations were found in adjacent diverticula. The evidence strongly suggests that corticosteroids can be responsible for ulceration and perforation of the colon either by direct injury or by interference with normal mechanisms of bowel repair."} {"id": "PMID:1267097", "title": "The sequential femoropopliteal bypass graft. A five year experience.", "content": "(1) A five year experience with sequential bypass grafts for femoropopliteal tibial reconstruction is presented. (2) Twenty-nine consecutive grafts were performed in twenty-eight patients in whom the saphenous vein was absent or inadequate for grafting purposes. (3) The series contains a high percentage of women (57 per cent), diabetics (39 per cent), and patients requiring surgery because of rest pain or tissue necrosis (83 per cent). (4) There was no operative mortality and no significant operative morbidity. (5) The overall graft patency rate is 71 per cent, which is comparable to that obtained with standard bypass technics. (6) There was no late failures in the ten grafts that survived one year or more. (7) This procedure appears to be a useful method for bypass grafting to the popliteal or tibial arteries below the knee when the saphenous vein is absent or inadequate.", "contents": "The sequential femoropopliteal bypass graft. A five year experience. (1) A five year experience with sequential bypass grafts for femoropopliteal tibial reconstruction is presented. (2) Twenty-nine consecutive grafts were performed in twenty-eight patients in whom the saphenous vein was absent or inadequate for grafting purposes. (3) The series contains a high percentage of women (57 per cent), diabetics (39 per cent), and patients requiring surgery because of rest pain or tissue necrosis (83 per cent). (4) There was no operative mortality and no significant operative morbidity. (5) The overall graft patency rate is 71 per cent, which is comparable to that obtained with standard bypass technics. (6) There was no late failures in the ten grafts that survived one year or more. (7) This procedure appears to be a useful method for bypass grafting to the popliteal or tibial arteries below the knee when the saphenous vein is absent or inadequate."} {"id": "PMID:1267099", "title": "Postgastrectomy syndromes.", "content": "Postgastrectomy syndromes requiring further operation are fortunately uncommon, as the symptoms are disabling and the results of corrective surgery are, at times, disappointing. Our sixty-six patients underwent a total of seventy-six procedures with forty-one successful results and thirty-five failures. Among the secessful group, only fourteen results were graded as excellent. (Table V.) Our experience, like that of others, demonstrates the necessity of accurate evaluation of the patient and of accurate syndrome classification. This not only allows the appropriate operation to be chosen but also helps to indicate those in whom operation should be avoided. Where more than one surgically remediable syndrome exists, simultaneous correction should be undertaken. Treatment of the mechanical problems of obstructed afferent loop by jejunojejunostomy and of stomal obstruction by complete stomal reconstruction provides satisfactory results. Roux-en-Y anastomosis is effective in patients with alkaline gastritis, but we caution against the use of this procedure in patients with vague symptoms and minimal endoscopic changes. Antiperistaltic jejunal reversal is the procedure of choice in managing severe postvagotomy diarrhea. Although most patients with dumping can be managed conservatively, a small number with severe symptoms and nutritional problems cannot and require further operation. Our experience with conversion from Billroth II to Billroth I and with isoperistaltic interposition, although minimal, has been reasonably satisfactory. Four groups of patients remain with symptoms of chronic vomiting, late postvagotomy atonic stomach, dumping \"plus,\" and miscellaneous symptoms. These patients have complaints that are difficult to define and usually have poor results with further operations. We believe that surgery should be avoided in these patients and that conservative measures be continued.", "contents": "Postgastrectomy syndromes. Postgastrectomy syndromes requiring further operation are fortunately uncommon, as the symptoms are disabling and the results of corrective surgery are, at times, disappointing. Our sixty-six patients underwent a total of seventy-six procedures with forty-one successful results and thirty-five failures. Among the secessful group, only fourteen results were graded as excellent. (Table V.) Our experience, like that of others, demonstrates the necessity of accurate evaluation of the patient and of accurate syndrome classification. This not only allows the appropriate operation to be chosen but also helps to indicate those in whom operation should be avoided. Where more than one surgically remediable syndrome exists, simultaneous correction should be undertaken. Treatment of the mechanical problems of obstructed afferent loop by jejunojejunostomy and of stomal obstruction by complete stomal reconstruction provides satisfactory results. Roux-en-Y anastomosis is effective in patients with alkaline gastritis, but we caution against the use of this procedure in patients with vague symptoms and minimal endoscopic changes. Antiperistaltic jejunal reversal is the procedure of choice in managing severe postvagotomy diarrhea. Although most patients with dumping can be managed conservatively, a small number with severe symptoms and nutritional problems cannot and require further operation. Our experience with conversion from Billroth II to Billroth I and with isoperistaltic interposition, although minimal, has been reasonably satisfactory. Four groups of patients remain with symptoms of chronic vomiting, late postvagotomy atonic stomach, dumping \"plus,\" and miscellaneous symptoms. These patients have complaints that are difficult to define and usually have poor results with further operations. We believe that surgery should be avoided in these patients and that conservative measures be continued."} {"id": "PMID:1267100", "title": "Colonic polypoid disease: need for total colonoscopy.", "content": "Colonoscopic examination of the entire colon was performed on 146 patients for radiographically suspected benign polypoid disease. Of thirty-six patients who did not have a neoplastic lesion at the suspected site, seven (19 per cent) had unsuspected small benign polypoid adenomas elsewhere in the colon. Of the remaining 110 patients who had a neoplastic lesion at the radiographically suspected site, 17 lesions (15 per cent) were either adenocarcinomas or neoplastic polyps with invasive carcinoma. One hundred twenty-eight additional unsuspected neoplastic polyps were found in 62 of the 110 patients (56 per cent). Six of the additional neoplastic lesions were either adenocarcinomas or polyps with invasive carcinoma. Four of these malignant lesions were in patients who had a benign polyp at the radiographically suspected site. Suspected colonic polypoid disease should be evaluated colonoscopically despite radiographic evidence of benignity. Colonoscopic evaluation in colonic polypoid disease should include examination of the entire colon with pathologic documentation of all polypoid lesions encountered.", "contents": "Colonic polypoid disease: need for total colonoscopy. Colonoscopic examination of the entire colon was performed on 146 patients for radiographically suspected benign polypoid disease. Of thirty-six patients who did not have a neoplastic lesion at the suspected site, seven (19 per cent) had unsuspected small benign polypoid adenomas elsewhere in the colon. Of the remaining 110 patients who had a neoplastic lesion at the radiographically suspected site, 17 lesions (15 per cent) were either adenocarcinomas or neoplastic polyps with invasive carcinoma. One hundred twenty-eight additional unsuspected neoplastic polyps were found in 62 of the 110 patients (56 per cent). Six of the additional neoplastic lesions were either adenocarcinomas or polyps with invasive carcinoma. Four of these malignant lesions were in patients who had a benign polyp at the radiographically suspected site. Suspected colonic polypoid disease should be evaluated colonoscopically despite radiographic evidence of benignity. Colonoscopic evaluation in colonic polypoid disease should include examination of the entire colon with pathologic documentation of all polypoid lesions encountered."} {"id": "PMID:1267101", "title": "Emergency aortic valve replacement.", "content": "The aortic valve was replaced as an emergency in twenty-seven patients between July 1970 and December 1974. Twenty-two patients had critical aortic stenosis and five had acute aortic insufficiency. The indications for emergency surgery were cardiac arrest in five patients, low cardiac output in four patients, and medically intractable pulmonary edema in eighteen patients. Cardiac catheterization was not undertaken in ten persons because of their critical condition. The clinical diagnosis in these patients was supported by noninvasive maneuvers. No surgical deaths occurred. Twenty-five patients are well, active and NYHA Class I at five to thirty-three months after surgery. There has been one late death and one patient has some residual exertional dyspnea. One patient required reoperation to relieve a clotted prosthetic valve. These results suggest that the patient with aortic valve disease may be offered a reasonable chance for survival, even when desperately ill.", "contents": "Emergency aortic valve replacement. The aortic valve was replaced as an emergency in twenty-seven patients between July 1970 and December 1974. Twenty-two patients had critical aortic stenosis and five had acute aortic insufficiency. The indications for emergency surgery were cardiac arrest in five patients, low cardiac output in four patients, and medically intractable pulmonary edema in eighteen patients. Cardiac catheterization was not undertaken in ten persons because of their critical condition. The clinical diagnosis in these patients was supported by noninvasive maneuvers. No surgical deaths occurred. Twenty-five patients are well, active and NYHA Class I at five to thirty-three months after surgery. There has been one late death and one patient has some residual exertional dyspnea. One patient required reoperation to relieve a clotted prosthetic valve. These results suggest that the patient with aortic valve disease may be offered a reasonable chance for survival, even when desperately ill."} {"id": "PMID:1267102", "title": "Markedly improved pulmonary function after open heart surgery in infancy utilizing surface cooling, profound hypothermia, and circulatory arrest.", "content": "The use of surface-induced profound hypothermia with limited cardiopulmonary bypass and circulatory arrest markedly diminished the need for mechanical ventilation for patients undergoing cardiac surgery. Eleven of twenty-two patients were extubated in the operating room and five more patients within 70 minutes postoperatively. Five patients required mechanical ventilation. Four of the five were extubated within 24 hours (mean, 19.05 hours); only one patient required mechanical ventilation greater than 24 hours. This experience would indicate that as the age of surgery is decreased, in conjunction with improved technics of cardiac surgery and anesthesia, the need for mechanical ventilation should be diminished.", "contents": "Markedly improved pulmonary function after open heart surgery in infancy utilizing surface cooling, profound hypothermia, and circulatory arrest. The use of surface-induced profound hypothermia with limited cardiopulmonary bypass and circulatory arrest markedly diminished the need for mechanical ventilation for patients undergoing cardiac surgery. Eleven of twenty-two patients were extubated in the operating room and five more patients within 70 minutes postoperatively. Five patients required mechanical ventilation. Four of the five were extubated within 24 hours (mean, 19.05 hours); only one patient required mechanical ventilation greater than 24 hours. This experience would indicate that as the age of surgery is decreased, in conjunction with improved technics of cardiac surgery and anesthesia, the need for mechanical ventilation should be diminished."} {"id": "PMID:1267116", "title": "[Clinical study on the shock organs in relation to the duration of shock (author's transl)].", "content": "To elucidate the mechanism of development of renal, pulmonary and liver insufficiency after serious shock, retrospective analysis was performed in 85 patients with traumatic shock. Among them, 14 patients died of renal, pulmonary or liver insufficiency after the resuscitation of shock, where kidney and lung were damaged concomitantly in most patients. There was a close correlation between the death related to both insufficiency and the duration of the shockp when the shock was treated completely within 10 hours, there was almost no death related to shock organ, but when the shock persisted more than 10 hours, the death rate was increased as the shock persisted longer. On the contrary, no relation was revealed between death caused by liver insufficiency and the duration of the shock. Renal and pulmonary functions were also correlated with the duration of the shock. It was revealed that the lower PaO2/PAO2 ratio was, the higher urea-N was in these patients, when shock persisted more than 10 hours. On the other hand, no relation was found between the change in liver function and the duration of shock. It can be concluded that the kidney and lung have the same nature as a shock organ. In general both functions were impaired concomitantly, where 10 hours of persistence could be regarded as the critical border to develop the shock organ. The liver seemed to be independent of the others as the shock organ, so that it should be discussed separately.", "contents": "[Clinical study on the shock organs in relation to the duration of shock (author's transl)]. To elucidate the mechanism of development of renal, pulmonary and liver insufficiency after serious shock, retrospective analysis was performed in 85 patients with traumatic shock. Among them, 14 patients died of renal, pulmonary or liver insufficiency after the resuscitation of shock, where kidney and lung were damaged concomitantly in most patients. There was a close correlation between the death related to both insufficiency and the duration of the shockp when the shock was treated completely within 10 hours, there was almost no death related to shock organ, but when the shock persisted more than 10 hours, the death rate was increased as the shock persisted longer. On the contrary, no relation was revealed between death caused by liver insufficiency and the duration of the shock. Renal and pulmonary functions were also correlated with the duration of the shock. It was revealed that the lower PaO2/PAO2 ratio was, the higher urea-N was in these patients, when shock persisted more than 10 hours. On the other hand, no relation was found between the change in liver function and the duration of shock. It can be concluded that the kidney and lung have the same nature as a shock organ. In general both functions were impaired concomitantly, where 10 hours of persistence could be regarded as the critical border to develop the shock organ. The liver seemed to be independent of the others as the shock organ, so that it should be discussed separately."} {"id": "PMID:1267117", "title": "[The concentrations of halothane in the operating theatre and its dependance on various methods of removal (author's transl)].", "content": "Measurement of halothane concentrations by means of gas chromatography was used to compare the efficiency of 1) a filtration system and 2) ducting of gases into the exhaust of the ventilation system of our operating threatre. The concentrations were found to be lower when the latter method was used. Measurements made subsequently provided data on halothane concentrations occurring during routine service when different methods of anaesthesia were used, with and without ducting of gases into the ventilation exhaust system.", "contents": "[The concentrations of halothane in the operating theatre and its dependance on various methods of removal (author's transl)]. Measurement of halothane concentrations by means of gas chromatography was used to compare the efficiency of 1) a filtration system and 2) ducting of gases into the exhaust of the ventilation system of our operating threatre. The concentrations were found to be lower when the latter method was used. Measurements made subsequently provided data on halothane concentrations occurring during routine service when different methods of anaesthesia were used, with and without ducting of gases into the ventilation exhaust system."} {"id": "PMID:1267118", "title": "Enflurane anaesthesia for removal of aldosterone producing adenoma.", "content": "In a 31-year old woman with a six year history of headache and hypertension a diagnosis of primary aldosteronism was made on the basis of urine samples containing 45 mug/day of aldosterone. The preoperative systemic blood pressure was 240 mm Hg systolic and 120 mm Hg diastolic. The serum potassium level was 2.6 mEq/L and other laboratory findings were within normal limits. The patient was to undergo operation. Pre-medication consisted of oral pentobarbitone, intramuscular pethidine and atropine. For induction of anaesthesia, enflurane 2.0-2.5% maximum was given with O2 (21/min) and N2O (61/min); no intravenous agents were used. Suxamethonium chloride 40 mg was administered to facilitate endotracheal intubation. Anaesthesia was maintained with enflurane 1.5-2.0% with 50% N2O and O2. Tubocurarine 27 mg was given for muscle relaxation. When the tumour was manipulated, systemic arterial blood pressure was elevated again to 190 mm Hg systolic and 120 mm Hg diastolic. After removal of the tumour, the arterial pressure and heart rate were stable and recovery from anaesthesia was without circulatory or respiratory complications. Plasma aldosterone levels reached a maximum when the tumour was manipulated and fell to normal levels on the second post-operative day. Cortisol levels were not altered markedly even when the tumour was handled. These data imply that adrenocortical response to enflurane anaesthesia as jadged by plasma aldosterone levels would be different from that as estimated by plasma cortisol levels.", "contents": "Enflurane anaesthesia for removal of aldosterone producing adenoma. In a 31-year old woman with a six year history of headache and hypertension a diagnosis of primary aldosteronism was made on the basis of urine samples containing 45 mug/day of aldosterone. The preoperative systemic blood pressure was 240 mm Hg systolic and 120 mm Hg diastolic. The serum potassium level was 2.6 mEq/L and other laboratory findings were within normal limits. The patient was to undergo operation. Pre-medication consisted of oral pentobarbitone, intramuscular pethidine and atropine. For induction of anaesthesia, enflurane 2.0-2.5% maximum was given with O2 (21/min) and N2O (61/min); no intravenous agents were used. Suxamethonium chloride 40 mg was administered to facilitate endotracheal intubation. Anaesthesia was maintained with enflurane 1.5-2.0% with 50% N2O and O2. Tubocurarine 27 mg was given for muscle relaxation. When the tumour was manipulated, systemic arterial blood pressure was elevated again to 190 mm Hg systolic and 120 mm Hg diastolic. After removal of the tumour, the arterial pressure and heart rate were stable and recovery from anaesthesia was without circulatory or respiratory complications. Plasma aldosterone levels reached a maximum when the tumour was manipulated and fell to normal levels on the second post-operative day. Cortisol levels were not altered markedly even when the tumour was handled. These data imply that adrenocortical response to enflurane anaesthesia as jadged by plasma aldosterone levels would be different from that as estimated by plasma cortisol levels."} {"id": "PMID:1267119", "title": "General anaesthesia for a patient with progressive muscular dystrophy.", "content": "The case is reported of a four-year-old boy with progressive muscular dystrophy who underwent anal fistulectomy under neuroleptanaesthesia with Thalamonal. Recovery was uneventful. Anaesthetic problems associated with the disease include sudden death due to myocardial involvement and high postoperative mortality due to pulmonary infection. Mental retardation and ECG abnormalities may be present and acute postoperative gastric dilatation has been reported. Narcotics or minor tranquilizers and hyoscine are recommended for premedication. Light anaesthesia should be maintained throughout surgery and minimal doses of non-depolarizing muscle relaxants may be used if necessary. Suxamethonium chloride should be avoided because muscle damage and cardiac arrest might occur.", "contents": "General anaesthesia for a patient with progressive muscular dystrophy. The case is reported of a four-year-old boy with progressive muscular dystrophy who underwent anal fistulectomy under neuroleptanaesthesia with Thalamonal. Recovery was uneventful. Anaesthetic problems associated with the disease include sudden death due to myocardial involvement and high postoperative mortality due to pulmonary infection. Mental retardation and ECG abnormalities may be present and acute postoperative gastric dilatation has been reported. Narcotics or minor tranquilizers and hyoscine are recommended for premedication. Light anaesthesia should be maintained throughout surgery and minimal doses of non-depolarizing muscle relaxants may be used if necessary. Suxamethonium chloride should be avoided because muscle damage and cardiac arrest might occur."} {"id": "PMID:1267120", "title": "[A further case of malignant hyperpyrexia and its treatment with lidocaine, methylprednisolone and verapamil (iproveratril) (author's transl)].", "content": "A dramatic case of anaesthetic-induced malignant hyperpyrexia is described. The treatment (ice packs, treatment of acidosis, glucose-insulin, methylprednisolone, lidocaine, verapamil, muscular relaxation and oxygen breathing) was effective. In the discussion, the pharmacological effects on the cardiac muscle are considered predominantly.", "contents": "[A further case of malignant hyperpyrexia and its treatment with lidocaine, methylprednisolone and verapamil (iproveratril) (author's transl)]. A dramatic case of anaesthetic-induced malignant hyperpyrexia is described. The treatment (ice packs, treatment of acidosis, glucose-insulin, methylprednisolone, lidocaine, verapamil, muscular relaxation and oxygen breathing) was effective. In the discussion, the pharmacological effects on the cardiac muscle are considered predominantly."} {"id": "PMID:1267121", "title": "[Simultaneous extra-corporeal oxygenation and haemodialysis in intesive medicine (a case report) (author's transl)].", "content": "In the field of intensive care there is a rise in the number of patients with distrubed or defunct vital functions, in whom multilateral therapy on traditional lines fails. The necessity of introducing new forms of treatment has been the occasion for the development of a universal perfusion device for temporary artificial multiple-organ substitution in the Faculty of Medicine at the Martin Luther University Halle-Wittenberg. This apparatus makes possible the substitution of, or support for, the functions of lungs, kidneys and liver singly or combined, via the extracorporeal treatment of the blood. The shortterm use of the apparatus is intended to provide, in addition to functional substitution of the organs, the best possible conditions for the regeneration of damaged organs. A critical account is given of the clinical application of the apparatus.", "contents": "[Simultaneous extra-corporeal oxygenation and haemodialysis in intesive medicine (a case report) (author's transl)]. In the field of intensive care there is a rise in the number of patients with distrubed or defunct vital functions, in whom multilateral therapy on traditional lines fails. The necessity of introducing new forms of treatment has been the occasion for the development of a universal perfusion device for temporary artificial multiple-organ substitution in the Faculty of Medicine at the Martin Luther University Halle-Wittenberg. This apparatus makes possible the substitution of, or support for, the functions of lungs, kidneys and liver singly or combined, via the extracorporeal treatment of the blood. The shortterm use of the apparatus is intended to provide, in addition to functional substitution of the organs, the best possible conditions for the regeneration of damaged organs. A critical account is given of the clinical application of the apparatus."} {"id": "PMID:1267122", "title": "[Control of the position of cava catheters by intraatrial ECG (author's transl)].", "content": "The precise position of a cava catheter can be defined by registration of electrocardiogramm by means of this catheter. The rather simple method by the use of a liquid filled catheter is briefly described, according to the improved method by Halter and Urthaler. Those electrocardiographic potentials, characteristic for each part of the right atrium, allow precise positioning of the tip of the catheter. By continuous registration of atrial electrocardiogram the catheter can be placed exactly between vena cava superior and right atrium. Furthermore, the possibility of registering atrial potentials by this simple means provides immediate recognition of atrial arrhythmias in cardian emmergencies.", "contents": "[Control of the position of cava catheters by intraatrial ECG (author's transl)]. The precise position of a cava catheter can be defined by registration of electrocardiogramm by means of this catheter. The rather simple method by the use of a liquid filled catheter is briefly described, according to the improved method by Halter and Urthaler. Those electrocardiographic potentials, characteristic for each part of the right atrium, allow precise positioning of the tip of the catheter. By continuous registration of atrial electrocardiogram the catheter can be placed exactly between vena cava superior and right atrium. Furthermore, the possibility of registering atrial potentials by this simple means provides immediate recognition of atrial arrhythmias in cardian emmergencies."} {"id": "PMID:1267123", "title": "[Ventricular fibrillation as complication of the application of a cava-catheter (author's transl)].", "content": "We report a case of ventricular fibrillation provoked by a cava catheter. Corresponding to literature we try to demonstrate the possibility of lethal cardiac arrhythmias being provoked by the cava catheter advancing into the right heart.", "contents": "[Ventricular fibrillation as complication of the application of a cava-catheter (author's transl)]. We report a case of ventricular fibrillation provoked by a cava catheter. Corresponding to literature we try to demonstrate the possibility of lethal cardiac arrhythmias being provoked by the cava catheter advancing into the right heart."} {"id": "PMID:1267124", "title": "[Closing volume and ventilatory distribution disturbances (author's transl)].", "content": "Ventilatory disturbances are induced by airway closure associated with an increase of the venous admixture from alveoli with a low ventilation-perfusion-ratio. Closing volume was measured by single breath nitrogen washout curves and correlated with ventilatory disturbances derived from multiple breath nitrogen washout curves and an inspiratory gas distribution index (IDI). There was present a close correlation between the closing volume in relation to the functional residual capacity and the IDI. With rising closing volume in relation to functional residual capacity a deterioration of the inspiratory gas distribution with increasing venous admixture was observed.", "contents": "[Closing volume and ventilatory distribution disturbances (author's transl)]. Ventilatory disturbances are induced by airway closure associated with an increase of the venous admixture from alveoli with a low ventilation-perfusion-ratio. Closing volume was measured by single breath nitrogen washout curves and correlated with ventilatory disturbances derived from multiple breath nitrogen washout curves and an inspiratory gas distribution index (IDI). There was present a close correlation between the closing volume in relation to the functional residual capacity and the IDI. With rising closing volume in relation to functional residual capacity a deterioration of the inspiratory gas distribution with increasing venous admixture was observed."} {"id": "PMID:1267186", "title": "Postnatal growth of the dorsal lateral geniculate nucleus of the cat.", "content": "The postnatal growth of the dorsal part of the lateral geniculate nucleus (LGNd) is studied in paraffin sections through the brains of 32 cats of known age. The changes in shape and position of the LGNd are described and it is shown that its volume increases from about 3.4 mm3 at birth to about 26.4 mm3 in the adult cat. When this value is corrected for shrinkage, the volume of the LGNd in the adult cat turns out to be about 44 mm3. The detailed measurements reveal that during the second and third week of postnatal life there is a particularly steep increase in volume and that the final values are already reached at around the 40th day. Concomitant with the increase in volume there is a decrease of the number of cells per unit volume of grey matter. In the binocular segment of lamina A the number of cells decreases from about 470 per (0.1 mm)3 at birth to between 95 and 130 per (0.1 mm)3 in the adult cat. Separate measurements of nerve cells and neuroglial cells indicate that the absolute number of nerve cells remains fairly constant during postnatal life, whereas between the second and sixth week a great number of neuroglial cells are newly formed.", "contents": "Postnatal growth of the dorsal lateral geniculate nucleus of the cat. The postnatal growth of the dorsal part of the lateral geniculate nucleus (LGNd) is studied in paraffin sections through the brains of 32 cats of known age. The changes in shape and position of the LGNd are described and it is shown that its volume increases from about 3.4 mm3 at birth to about 26.4 mm3 in the adult cat. When this value is corrected for shrinkage, the volume of the LGNd in the adult cat turns out to be about 44 mm3. The detailed measurements reveal that during the second and third week of postnatal life there is a particularly steep increase in volume and that the final values are already reached at around the 40th day. Concomitant with the increase in volume there is a decrease of the number of cells per unit volume of grey matter. In the binocular segment of lamina A the number of cells decreases from about 470 per (0.1 mm)3 at birth to between 95 and 130 per (0.1 mm)3 in the adult cat. Separate measurements of nerve cells and neuroglial cells indicate that the absolute number of nerve cells remains fairly constant during postnatal life, whereas between the second and sixth week a great number of neuroglial cells are newly formed."} {"id": "PMID:1267187", "title": "The vestibular nuclei in the domestic hen (Gallus domesticus). I. Normal anatomy.", "content": "The topography and the cyto- and fiber architecture of the vestibular nuclear complex in the domestic hen are described as seen in transverse and horizontal thionine and myelin impregnated section. The subdivision of the nuclear complex arrived at from these studies is discussed the light of some experimental studies of the fiber connection of the vestibular nuclei in birds and compared with the well known organization of the vestibular nuclei in mammals. Six main vestibular nuclei are identified, the superior nucleus, the nucleus Deiters ventralis, the nucleus Deiters dorsalis, the tangential nucleus, the medial nucleus and the descending nucleus. In addition two cell groups (the cell group A and B) lying in close relation to the other nuclei are described and considered as parts of the vestibular complex. The map of the vestibular complex arrived at is largely in agreement with the maps presented by most earlier authors on other species. Furthermore, it appears that the organization of the vestibular complex in birds is more similar to the organization of the complex in mammals than hitherto recognized.", "contents": "The vestibular nuclei in the domestic hen (Gallus domesticus). I. Normal anatomy. The topography and the cyto- and fiber architecture of the vestibular nuclear complex in the domestic hen are described as seen in transverse and horizontal thionine and myelin impregnated section. The subdivision of the nuclear complex arrived at from these studies is discussed the light of some experimental studies of the fiber connection of the vestibular nuclei in birds and compared with the well known organization of the vestibular nuclei in mammals. Six main vestibular nuclei are identified, the superior nucleus, the nucleus Deiters ventralis, the nucleus Deiters dorsalis, the tangential nucleus, the medial nucleus and the descending nucleus. In addition two cell groups (the cell group A and B) lying in close relation to the other nuclei are described and considered as parts of the vestibular complex. The map of the vestibular complex arrived at is largely in agreement with the maps presented by most earlier authors on other species. Furthermore, it appears that the organization of the vestibular complex in birds is more similar to the organization of the complex in mammals than hitherto recognized."} {"id": "PMID:1267188", "title": "Effect of chronic centrifugation on the structural development of the musculoskeletal system of the rat.", "content": "25 female Sprague-Dawley rats were placed on a 3.66 m radius centrifuge and subsequently exposed almost continuously for 810 days to 2.76 G. Compared to normal gravity controls, the most noticeable effect of hypergravity was the inhibition of growth of the centrifuged animals. The rats exposed to hypergravity showed on average a smaller femur length (-6.5%), a smaller cross-sectional area (-7.7%, when expressed linearly, i. e. (area/pi)1/2), and smaller outer and inner cross-sectional radii (linearly -9.3% and -12.3%) at the mid-shaft of the femoral bones. The growth inhibition of 3 hind-leg muscles was on average significantly less ranging from (-3.5% to -4.1%), compared to the growth inhibition of the linear dimension of the femur. Statistically there was no difference in the slope and elevation of the regression of the square-root of the cross-sectional area divided by pi on the length of the femur between centrifuged animals and their 16 age matched controls. In the weight control group of 24 animals, comprised of 34,74, and 102 day old rats, the corresponding regression line was parallel and lower in elevation by -12.8%, compared to the line for the centrifuged and age control groups. But, compared to the regression derived from all control animals ranging from 34 to 840 days of age, the cross-sectional area at the mid-shaft of the femur was 8.4% greater in the rats exposed to 2.76 G for 810 days. The slopes of the regression of the outer radius at mid-shaft on the length of the femur were the same in the centrifuged group and in the weight and age control groups of animals. But, the regression lines differed in elevation by -4.4% on average between the centrifuged and age control animals. The line for the regression of the inner radius at the mid-shaft on the length of the femur was parallel and lower in elevation by -7.6% in the centrifuged animals compared to the line for the age controls. But, compared to all control animals living at normal gravity, the outer radius was increased by 3.0% and the inner radius was decreased by 5.7% in the animals exposed to 2.76 G for 810 days. Since the centrifuged animals were all 840 days old, while the controls were from 34 to 840 days old, only further experiments comparing centrifuged and control animals of the same age at various growth stages will be able to furnish evidence for an unambiguous bone hypertrophy. The regressions of the cube-root of body weight on length of the femur deviate significantly in the 3 groups of animals. The heavier rats of the age control group have relatively shorter femurs than the lighter animals. The opposite applies to the centrifuged and the weight control groups of rats. Although the rats on the centrifuge are markedly smaller in overall body size than the controls, they exhibit on average the same absolute muscle weights as the animals at earth gravity, if rats of the same overall body size are compared...", "contents": "Effect of chronic centrifugation on the structural development of the musculoskeletal system of the rat. 25 female Sprague-Dawley rats were placed on a 3.66 m radius centrifuge and subsequently exposed almost continuously for 810 days to 2.76 G. Compared to normal gravity controls, the most noticeable effect of hypergravity was the inhibition of growth of the centrifuged animals. The rats exposed to hypergravity showed on average a smaller femur length (-6.5%), a smaller cross-sectional area (-7.7%, when expressed linearly, i. e. (area/pi)1/2), and smaller outer and inner cross-sectional radii (linearly -9.3% and -12.3%) at the mid-shaft of the femoral bones. The growth inhibition of 3 hind-leg muscles was on average significantly less ranging from (-3.5% to -4.1%), compared to the growth inhibition of the linear dimension of the femur. Statistically there was no difference in the slope and elevation of the regression of the square-root of the cross-sectional area divided by pi on the length of the femur between centrifuged animals and their 16 age matched controls. In the weight control group of 24 animals, comprised of 34,74, and 102 day old rats, the corresponding regression line was parallel and lower in elevation by -12.8%, compared to the line for the centrifuged and age control groups. But, compared to the regression derived from all control animals ranging from 34 to 840 days of age, the cross-sectional area at the mid-shaft of the femur was 8.4% greater in the rats exposed to 2.76 G for 810 days. The slopes of the regression of the outer radius at mid-shaft on the length of the femur were the same in the centrifuged group and in the weight and age control groups of animals. But, the regression lines differed in elevation by -4.4% on average between the centrifuged and age control animals. The line for the regression of the inner radius at the mid-shaft on the length of the femur was parallel and lower in elevation by -7.6% in the centrifuged animals compared to the line for the age controls. But, compared to all control animals living at normal gravity, the outer radius was increased by 3.0% and the inner radius was decreased by 5.7% in the animals exposed to 2.76 G for 810 days. Since the centrifuged animals were all 840 days old, while the controls were from 34 to 840 days old, only further experiments comparing centrifuged and control animals of the same age at various growth stages will be able to furnish evidence for an unambiguous bone hypertrophy. The regressions of the cube-root of body weight on length of the femur deviate significantly in the 3 groups of animals. The heavier rats of the age control group have relatively shorter femurs than the lighter animals. The opposite applies to the centrifuged and the weight control groups of rats. Although the rats on the centrifuge are markedly smaller in overall body size than the controls, they exhibit on average the same absolute muscle weights as the animals at earth gravity, if rats of the same overall body size are compared..."} {"id": "PMID:1267189", "title": "Effect of chronic centrifugation of the musculoskeletal system of the dog.", "content": "Sixteen male Beagle dogs, 293 to 509 days old, were exposed almost continuously for 3 months to 2.0 G on a 7.9 meter radius centrifuge. The dogs were maintained on the centrifuge, by means of a specially designed automated waste disposal and life support system. As compared to the mean values of normal gravity controls, centrifuged dogs showed no differences in femur length; cross-sectional area, outer and inner radii at mid-shaft of the femur; dry weights of the biceps femoris, quadriceps femoris, and gastrocnemius muscles. It was shown by analysis of covariance that chronic centrifugation has no effect on the relationship between the length and the cross-sectional dimensions at mid-shaft of the femur. Photon absorptiometry, however, revealed significant mineral content increases averaging 1.5% at 3 sites, i.e., at the 1/4, 1/2 and 3/4 length of the femur.", "contents": "Effect of chronic centrifugation of the musculoskeletal system of the dog. Sixteen male Beagle dogs, 293 to 509 days old, were exposed almost continuously for 3 months to 2.0 G on a 7.9 meter radius centrifuge. The dogs were maintained on the centrifuge, by means of a specially designed automated waste disposal and life support system. As compared to the mean values of normal gravity controls, centrifuged dogs showed no differences in femur length; cross-sectional area, outer and inner radii at mid-shaft of the femur; dry weights of the biceps femoris, quadriceps femoris, and gastrocnemius muscles. It was shown by analysis of covariance that chronic centrifugation has no effect on the relationship between the length and the cross-sectional dimensions at mid-shaft of the femur. Photon absorptiometry, however, revealed significant mineral content increases averaging 1.5% at 3 sites, i.e., at the 1/4, 1/2 and 3/4 length of the femur."} {"id": "PMID:1267190", "title": "On the variability of form and vascularization of the cat carotid body.", "content": "The compact carotid body shows, according to the source of the animals, a variability with respect to location, shape and vascularization which is similar to that found in the human carotid body and that of the dog. Aside from the ovoid forms which had been assumed to be characteristic, carotid bodies were found which either lie flat on the stem vessel or embrace it. Vascular supply is achieved not only by the occipito-pharyngeal trunk but also by the external carotid, ascendent pharyngeal and occipital arteries via one to more than three side branches. The findings are also relevant for the physiological investigation since they reveal that the function of the carotid body does not closely depend on its marcro architecture.", "contents": "On the variability of form and vascularization of the cat carotid body. The compact carotid body shows, according to the source of the animals, a variability with respect to location, shape and vascularization which is similar to that found in the human carotid body and that of the dog. Aside from the ovoid forms which had been assumed to be characteristic, carotid bodies were found which either lie flat on the stem vessel or embrace it. Vascular supply is achieved not only by the occipito-pharyngeal trunk but also by the external carotid, ascendent pharyngeal and occipital arteries via one to more than three side branches. The findings are also relevant for the physiological investigation since they reveal that the function of the carotid body does not closely depend on its marcro architecture."} {"id": "PMID:1267191", "title": "Early terminal degeneration of cerebellar climbing fibers after destruction of the inferior olive in the rat. Synaptic relationships in the molecular layer.", "content": "The cerebellar molecular layer in adult rats has been studied with the electron microscope at several early and consecutive survival times following 3-acetylpyridine intoxication. Climbing fiber (CF) terminals underwent a fast process of electron-dense degeneration which became apparent from 16 hours onwards. A small proportion of degenerating terminals were depleted of vesicles and filled with a dark flocculent and granular homogeneous matrix. Microtubular changes in degenerating CF tendrils were observed. CF terminals were found in relation with every Purkinje cell in normal animals and completely disappeared within 72 hours after the treatment. CF synapses were found on Purkinje dendritic and somatic thorns, sometimes also on the dendritic shafts or even on the Purkinje soma. Convincing evidencd of synaptic contacts of CF varicosities on either basket or stellate cells could not be obtained. CF synapses with Golgi II cell dendrites in the molecular layer were described. Decrease in the number of post-synaptic dendritic thorns normally assigned for CF synapses was observed consequential to CF anterograde degeneration. The observations are consistent with previous conclusions drawn from light microscopic studies that the clearing up of CF debris in the molecular layer is completed within the short time of three days, and that the inferior olive seems to be the only source of CFs.", "contents": "Early terminal degeneration of cerebellar climbing fibers after destruction of the inferior olive in the rat. Synaptic relationships in the molecular layer. The cerebellar molecular layer in adult rats has been studied with the electron microscope at several early and consecutive survival times following 3-acetylpyridine intoxication. Climbing fiber (CF) terminals underwent a fast process of electron-dense degeneration which became apparent from 16 hours onwards. A small proportion of degenerating terminals were depleted of vesicles and filled with a dark flocculent and granular homogeneous matrix. Microtubular changes in degenerating CF tendrils were observed. CF terminals were found in relation with every Purkinje cell in normal animals and completely disappeared within 72 hours after the treatment. CF synapses were found on Purkinje dendritic and somatic thorns, sometimes also on the dendritic shafts or even on the Purkinje soma. Convincing evidencd of synaptic contacts of CF varicosities on either basket or stellate cells could not be obtained. CF synapses with Golgi II cell dendrites in the molecular layer were described. Decrease in the number of post-synaptic dendritic thorns normally assigned for CF synapses was observed consequential to CF anterograde degeneration. The observations are consistent with previous conclusions drawn from light microscopic studies that the clearing up of CF debris in the molecular layer is completed within the short time of three days, and that the inferior olive seems to be the only source of CFs."} {"id": "PMID:1267192", "title": "Mechanical properties and histology of cortical bone from younger and older men.", "content": "Tensile breaking load, strength, strain, modulus of elasticity and density plus the histological structure at the fracture site, were determined for 207 standardized specimens of cortical bone from the embalmed femur, tibia, and fibula of 17 men from 36 to 75 years of age. The men were divided into a younger group (41.5 years old-avg)) and an older group (71 years old-avg). Specimens from younger men had a greater average breaking load, strength, strain, modulus and density than those from older men. The percentage of spaces in the break area was greater in specimens from older men, but specimens from younger men had a slightly greater percentage of osteons, osteon fragments, and interstitial lamellae. The number of osteons/mm2 and of osteon fragments/mm2 was greater in specimens from older men but the average area/osteon and area/osteon fragment was greater in specimens from younger men. Thus, there are quantitative and qualitative differences in the histological structure of bone from younger and older men. Differences in the tensile properties of bone from younger and older men can be explained by histological differences in the bone.", "contents": "Mechanical properties and histology of cortical bone from younger and older men. Tensile breaking load, strength, strain, modulus of elasticity and density plus the histological structure at the fracture site, were determined for 207 standardized specimens of cortical bone from the embalmed femur, tibia, and fibula of 17 men from 36 to 75 years of age. The men were divided into a younger group (41.5 years old-avg)) and an older group (71 years old-avg). Specimens from younger men had a greater average breaking load, strength, strain, modulus and density than those from older men. The percentage of spaces in the break area was greater in specimens from older men, but specimens from younger men had a slightly greater percentage of osteons, osteon fragments, and interstitial lamellae. The number of osteons/mm2 and of osteon fragments/mm2 was greater in specimens from older men but the average area/osteon and area/osteon fragment was greater in specimens from younger men. Thus, there are quantitative and qualitative differences in the histological structure of bone from younger and older men. Differences in the tensile properties of bone from younger and older men can be explained by histological differences in the bone."} {"id": "PMID:1267193", "title": "Kinetics of intraepithelial lymphocytes in the small intestine of thymus-deprived mice and antigen-deprived mice.", "content": "The kinetics of lymphoid cells within the epithelium of the small gut has been studied in various thymus-deprived mice and in antigen-deprived mice by the use of 3H-thymidine injections and radioautography. In thymus-deprived mice--including adult thymectomized, thymectomized and irradiated, neonatally thymectomized, and nude mice - and in germ-free mice decreased numbers of intraepithelial lymphocytes (IL) were found. On the other hand, the radioautographic results indicated that the remaining IL populations included both newly formed and long-lived lymphoid cells in the same percentages as found in sham-operated controls and normal mice. It is concluded that although the presence of the thymus and the antigen content of the gut is of importance to the maintenance of the numbers of cells in the lymphoid populations of the intestinal wall, the basic kinetics of these cell populations are preserved in deprived mice.", "contents": "Kinetics of intraepithelial lymphocytes in the small intestine of thymus-deprived mice and antigen-deprived mice. The kinetics of lymphoid cells within the epithelium of the small gut has been studied in various thymus-deprived mice and in antigen-deprived mice by the use of 3H-thymidine injections and radioautography. In thymus-deprived mice--including adult thymectomized, thymectomized and irradiated, neonatally thymectomized, and nude mice - and in germ-free mice decreased numbers of intraepithelial lymphocytes (IL) were found. On the other hand, the radioautographic results indicated that the remaining IL populations included both newly formed and long-lived lymphoid cells in the same percentages as found in sham-operated controls and normal mice. It is concluded that although the presence of the thymus and the antigen content of the gut is of importance to the maintenance of the numbers of cells in the lymphoid populations of the intestinal wall, the basic kinetics of these cell populations are preserved in deprived mice."} {"id": "PMID:1267194", "title": "Variation in form of circle of Willis: some anatomical and embryological considerations.", "content": "This work is based on a study of 62 circles of Willis (circulus arteriosus cerebri) from patients dead from diverse causes. We have described the wide diversity of variations found to be present in the arterial vessels that form the circle, we presented the frequency of the different variations, and finally we discuss the possible ontogenic cause of these variations.", "contents": "Variation in form of circle of Willis: some anatomical and embryological considerations. This work is based on a study of 62 circles of Willis (circulus arteriosus cerebri) from patients dead from diverse causes. We have described the wide diversity of variations found to be present in the arterial vessels that form the circle, we presented the frequency of the different variations, and finally we discuss the possible ontogenic cause of these variations."} {"id": "PMID:1267195", "title": "Alterations in the fine structure of the prostate and seminal vesicle of rats treated with cyproterone acetate.", "content": "Young adult male rats were treated with daily injections of 10 mg of cyproterone acetate for periods up to 16 weeks. Samples of the ventral prostate and the seminal vesicle were studied with the light and electron microscopes. Alterations visible with the light microscope included decreases in cell size, cytoplasmic basophilia, the size of the nucleolus, and the amount of luminal secretory material. Ultrastructural changes in the epithelium of both glands involved mainly the organelles that participate in the formation of secretions. Large declines were observed in the abundance of rough endoplasmic reticulum, size of the Golgi apparatus, and number of secretory vacuoles. Lipid droplets accumulated in the seminal vesicle epithelium, and lysosomes were numerous in both glands. Changes were first observed microscopically in the seminal vesicle after one week and in the prostate after two or three weeks. Maximal development of the alteration occurred after treatment for approximately eight weeks.", "contents": "Alterations in the fine structure of the prostate and seminal vesicle of rats treated with cyproterone acetate. Young adult male rats were treated with daily injections of 10 mg of cyproterone acetate for periods up to 16 weeks. Samples of the ventral prostate and the seminal vesicle were studied with the light and electron microscopes. Alterations visible with the light microscope included decreases in cell size, cytoplasmic basophilia, the size of the nucleolus, and the amount of luminal secretory material. Ultrastructural changes in the epithelium of both glands involved mainly the organelles that participate in the formation of secretions. Large declines were observed in the abundance of rough endoplasmic reticulum, size of the Golgi apparatus, and number of secretory vacuoles. Lipid droplets accumulated in the seminal vesicle epithelium, and lysosomes were numerous in both glands. Changes were first observed microscopically in the seminal vesicle after one week and in the prostate after two or three weeks. Maximal development of the alteration occurred after treatment for approximately eight weeks."} {"id": "PMID:1267196", "title": "Recovery of rat prolactin cells following cessation of estrogen treatment.", "content": "Estrogen treatment for one month in female rats caused some regression of somatotrophs, but induced an increase in the number of prolactin cells and caused these cells to hypertrophy. These stimulated prolactin cells showed extensive development of the granular endoplasmic reticulum which was often arranged in concentric whorls (Nebenkern). Most of the prolactin cells contained a small number of mature granules which were smaller in size than those of prolactin cells in control animals. These prolactin granules were round in sectioned profile and closely resembled the secretory granules of normal somatotrophs.", "contents": "Recovery of rat prolactin cells following cessation of estrogen treatment. Estrogen treatment for one month in female rats caused some regression of somatotrophs, but induced an increase in the number of prolactin cells and caused these cells to hypertrophy. These stimulated prolactin cells showed extensive development of the granular endoplasmic reticulum which was often arranged in concentric whorls (Nebenkern). Most of the prolactin cells contained a small number of mature granules which were smaller in size than those of prolactin cells in control animals. These prolactin granules were round in sectioned profile and closely resembled the secretory granules of normal somatotrophs."} {"id": "PMID:1267197", "title": "The skin of the giraffe.", "content": "The skin of the giraffe has the same general histological structure as that of other mammals, but there are notable features. The skin is heavily pigmented with the epidermis, pilary canals, and the outer cell layer of the apocrine duct richly melanized. Furthermore, melanotic dendritic cells are frequently found in the sebaceous glands, the entire length of the external root sheath, and the secretory tubules of the apocrine glands. The thick skin has a papillary dermis that extends to just beneath the secretory coils of the apocrine glands and bulbs of hair follicles and an equally thick reticular layer below these structures. The hair follicles do not grow in clusters, and with some regional variations, have associated sebaceous glands, apocrine glands, and arrectores pilorum muscles. Only the large hairs have a prominent medulla. In such specialized regions as the eyelids, nose, and lips, the apocrine glands are surrounded by cholinesterase-reactive nerves but the glands on the general body surface are not. The only specialized nerve receptors are hair follicle end organs found on every hair of the eyelids, nose, and lips, but only rarely elsewhere.", "contents": "The skin of the giraffe. The skin of the giraffe has the same general histological structure as that of other mammals, but there are notable features. The skin is heavily pigmented with the epidermis, pilary canals, and the outer cell layer of the apocrine duct richly melanized. Furthermore, melanotic dendritic cells are frequently found in the sebaceous glands, the entire length of the external root sheath, and the secretory tubules of the apocrine glands. The thick skin has a papillary dermis that extends to just beneath the secretory coils of the apocrine glands and bulbs of hair follicles and an equally thick reticular layer below these structures. The hair follicles do not grow in clusters, and with some regional variations, have associated sebaceous glands, apocrine glands, and arrectores pilorum muscles. Only the large hairs have a prominent medulla. In such specialized regions as the eyelids, nose, and lips, the apocrine glands are surrounded by cholinesterase-reactive nerves but the glands on the general body surface are not. The only specialized nerve receptors are hair follicle end organs found on every hair of the eyelids, nose, and lips, but only rarely elsewhere."} {"id": "PMID:1267198", "title": "Microblebs of intestinal epithelial cell microvilli of Citellus tridecemlineatus.", "content": "The presence of microblebs arising from the lateral surfaces and tips of microvilli of intestinal epithelial cells of thirteen-lined ground squirrels. Citellus tridecemlineatus, is reported. Microblebs measure approximately 50 nm in diameter and are bounded by a unit membrane which is continuous with the unit plasma membrane of the microvilli. It is suggested that such microblebbing reflects the rapid turnover of microvillar contents, membrane and surface coat.", "contents": "Microblebs of intestinal epithelial cell microvilli of Citellus tridecemlineatus. The presence of microblebs arising from the lateral surfaces and tips of microvilli of intestinal epithelial cells of thirteen-lined ground squirrels. Citellus tridecemlineatus, is reported. Microblebs measure approximately 50 nm in diameter and are bounded by a unit membrane which is continuous with the unit plasma membrane of the microvilli. It is suggested that such microblebbing reflects the rapid turnover of microvillar contents, membrane and surface coat."} {"id": "PMID:1267199", "title": "Fine structure of tracheo-bronchial epithelial nerves of the cat.", "content": "The nerves in and immediately under the epithelial layer of the trachea and primary bronchi of the cat are studied with the electron microscope. The axons are unmyelinated and contain microtubules and mitochondria. Epithelial axons are observed throughout the entire epithelial layer, but, are usually concentrated in the basal area immediately above the basal lamina. Most axons are near the basal cells; others are in the vicinity of granulated cells or occur in the intercellular spaces between other columnar cells. A few of the epithelial axons are large and crowded with axoplasmic mitochondria. The possibility that some epithelial axons may have sensory functions is discussed.", "contents": "Fine structure of tracheo-bronchial epithelial nerves of the cat. The nerves in and immediately under the epithelial layer of the trachea and primary bronchi of the cat are studied with the electron microscope. The axons are unmyelinated and contain microtubules and mitochondria. Epithelial axons are observed throughout the entire epithelial layer, but, are usually concentrated in the basal area immediately above the basal lamina. Most axons are near the basal cells; others are in the vicinity of granulated cells or occur in the intercellular spaces between other columnar cells. A few of the epithelial axons are large and crowded with axoplasmic mitochondria. The possibility that some epithelial axons may have sensory functions is discussed."} {"id": "PMID:1267200", "title": "Ciliated and secretory epidermis produced from embryonic mammalian skin in organ culture by vitamin A.", "content": "When skin from the upper lip of 12-day embryonic mice was grown for ten days in organ culture with 5.7 mug retinol added per ml of biological medium, keratinization was suppressed and a ciliated and secretory epithelium was produced. Ultrastructural features of this epithelium are described. At this very early stage mouse epidermis is thus similar of chick epidermis in its ability to undergo radical metaplasia in response to vitamin A.", "contents": "Ciliated and secretory epidermis produced from embryonic mammalian skin in organ culture by vitamin A. When skin from the upper lip of 12-day embryonic mice was grown for ten days in organ culture with 5.7 mug retinol added per ml of biological medium, keratinization was suppressed and a ciliated and secretory epithelium was produced. Ultrastructural features of this epithelium are described. At this very early stage mouse epidermis is thus similar of chick epidermis in its ability to undergo radical metaplasia in response to vitamin A."} {"id": "PMID:1267201", "title": "Metabolism of methoxyflurane in man.", "content": "Excretion of methoxyflurane was studied in 12 patients receiving anesthesia in a closed rebreathing circuit at a constant alveolar concentration of approximately 0.24 per cent. The mean methoxyflurane uptake was 18 g (range 7.6-31 g) during a mean time of anesthesia administration of 2 hours, 18 minutes (range 55-309 minutes). An average of 19 per cent of the uptake was recovered unchanged in the exhaled air after anesthesia. Urinary excretion of organic fluorine, fluoride, and oxalic acid was equivalent to 29, 7.7 and 7.1 per cent of methoxyflurane uptake, respectively. Approximately a third of the uptake remained unrecovered. It is postulated that a portion of the unrecovered drug became permanently bound to tissues and hence its excretion was delayed beyond the period of the study.", "contents": "Metabolism of methoxyflurane in man. Excretion of methoxyflurane was studied in 12 patients receiving anesthesia in a closed rebreathing circuit at a constant alveolar concentration of approximately 0.24 per cent. The mean methoxyflurane uptake was 18 g (range 7.6-31 g) during a mean time of anesthesia administration of 2 hours, 18 minutes (range 55-309 minutes). An average of 19 per cent of the uptake was recovered unchanged in the exhaled air after anesthesia. Urinary excretion of organic fluorine, fluoride, and oxalic acid was equivalent to 29, 7.7 and 7.1 per cent of methoxyflurane uptake, respectively. Approximately a third of the uptake remained unrecovered. It is postulated that a portion of the unrecovered drug became permanently bound to tissues and hence its excretion was delayed beyond the period of the study."} {"id": "PMID:1267202", "title": "Kinetics of methoxyflurane biotransformation with reference to substrate inhibition.", "content": "The kinetics of biotransformation of methoxyflurane by rat hepatic microsomes in vitro was studied. The rate of biotransformation as measured by analysis of metabolites continued to increase even at near-saturation concentrations of the anesthetic. Methoxyflurane biotransformation followed either an unbounded curve with empirical formula y = a ln(bx + 1) or an asymptotic curve with formula (see article) No substrate inhibition was observed. Total fluoride Vmax of 135.1 mmumol F-/mg protein/30' was increased to 931.9 by phenobarbital induction; free fluoride Vmax from 39.2 to 403.2. Thus, enzyme induction shifted biotransformation to the production of greater amounts of inorganic free fluoride metabolites than organic fluoride-containing metabolites. Phenobarbital induction caused qualitative as well as quantitative alteration in the biotransformation of methoxyflurane.", "contents": "Kinetics of methoxyflurane biotransformation with reference to substrate inhibition. The kinetics of biotransformation of methoxyflurane by rat hepatic microsomes in vitro was studied. The rate of biotransformation as measured by analysis of metabolites continued to increase even at near-saturation concentrations of the anesthetic. Methoxyflurane biotransformation followed either an unbounded curve with empirical formula y = a ln(bx + 1) or an asymptotic curve with formula (see article) No substrate inhibition was observed. Total fluoride Vmax of 135.1 mmumol F-/mg protein/30' was increased to 931.9 by phenobarbital induction; free fluoride Vmax from 39.2 to 403.2. Thus, enzyme induction shifted biotransformation to the production of greater amounts of inorganic free fluoride metabolites than organic fluoride-containing metabolites. Phenobarbital induction caused qualitative as well as quantitative alteration in the biotransformation of methoxyflurane."} {"id": "PMID:1267203", "title": "Inhibition of cell-mediated cytotoxicity by halothane and nitrous oxide.", "content": "Killing of tumor cells by lymphoid cells is important in cell-mediated immunity and defense against cancer. The authors determined that halothane, in vitro, inhibits the killing of YAAC-1 ascites tumor cells from A/jax mice by sensitized peritoneal exudate cells from C57/Black/6 mice. Lysis of tumor cells was quantitated by release of 51Cr into the culture medium. Inhibition of cell-mediated cytotoxicity ranged from 5 per cent in 0.5 per cent halothane to 44.7 per cent in 2.5 per cent halothane exposure. A 12 per cent inhibition of cytotoxicity by 80 per cent nitrous oxide was not statistically significant, but was of a magnitude near that of an equipotent concentration of halothane. The inhibition of cytotoxicity by halothane and nitrous oxide observed in vitro may partially account for the inhibition of cytotoxicity observed when patients undergo surgical operation.", "contents": "Inhibition of cell-mediated cytotoxicity by halothane and nitrous oxide. Killing of tumor cells by lymphoid cells is important in cell-mediated immunity and defense against cancer. The authors determined that halothane, in vitro, inhibits the killing of YAAC-1 ascites tumor cells from A/jax mice by sensitized peritoneal exudate cells from C57/Black/6 mice. Lysis of tumor cells was quantitated by release of 51Cr into the culture medium. Inhibition of cell-mediated cytotoxicity ranged from 5 per cent in 0.5 per cent halothane to 44.7 per cent in 2.5 per cent halothane exposure. A 12 per cent inhibition of cytotoxicity by 80 per cent nitrous oxide was not statistically significant, but was of a magnitude near that of an equipotent concentration of halothane. The inhibition of cytotoxicity by halothane and nitrous oxide observed in vitro may partially account for the inhibition of cytotoxicity observed when patients undergo surgical operation."} {"id": "PMID:1267204", "title": "Absence of cellular hypersensitivity in patients with unexplained hepatitis following halothane.", "content": "In-vitro tests of cell-mediated immunity were performed using blood obtained from subjects with unexplained hepatitis following halothane anesthesia to determine whether sensitization to potentially antigenic products of halothane metabolism might exist. Both lymphocyte transformation and leukocyte migration-inhibition tests were undertaken in the presence of trifluoroacetylated human serum albumin. All tests in the presence of these potential antigenic complexes were negative. The results support the view that cell-mediated hypersensitivity to trifluoroacetylated proteins does not contribute to the pathogenesis of hepatic dysfunction following halothane anesthesia.", "contents": "Absence of cellular hypersensitivity in patients with unexplained hepatitis following halothane. In-vitro tests of cell-mediated immunity were performed using blood obtained from subjects with unexplained hepatitis following halothane anesthesia to determine whether sensitization to potentially antigenic products of halothane metabolism might exist. Both lymphocyte transformation and leukocyte migration-inhibition tests were undertaken in the presence of trifluoroacetylated human serum albumin. All tests in the presence of these potential antigenic complexes were negative. The results support the view that cell-mediated hypersensitivity to trifluoroacetylated proteins does not contribute to the pathogenesis of hepatic dysfunction following halothane anesthesia."} {"id": "PMID:1267205", "title": "Pharmacokinetics of naloxone in rats and in man: basis for its potency and short duration of action.", "content": "Using a specific and sensitive radioimmunoassay, naloxone concentrations in the brains and sera of rats were measured at intervals for four hours following iv injection (5 mg/kg). Decrement curves of naloxone were compared with those after iv injection of morphine (5 mg/kg). Serum concentration of naloxone at 5 minutes was 1.45 +/- 0.1 mug/ml (mean +/- SE) and that of morphine was 1.0 +/- 0.08 mug/ml. Their serum half-lives from one to four hours were approximately the same, 30-40 minutes. With naloxone, the brain-serum concentration ratios ranged from 2.7 to 4.6. Concentration of naloxone in the brain declined parallel to that in the serum. However, with morphine the initial brain concentration was approximately one tenth that in the serum (0.096 +/- 0.04 mug/ml). The brain morphine concentration was sustained for one hour, while serum morphine concentrations declined from 1.0 to 0.19 mug/ml during this period. Two minutes after iv injection of naloxone HCl (0.4 mg) in nine healthy volunteers, the serum drug concentration was 0.01 +/- .001 mug/ml. At 5 minutes, 97 per cent of the administered dose was no longer found in the serum, the serum concentration being 0.004 +/- .0003 mug/ml. From 20 minutes to two hours after injection, the calculated mean serum half-life of naloxone was 64 minutes. These results suggest that the rapid penetrance of naloxone into the brain and the high brain-serum concentration ratio contribute to its rapid onset of action and potency as a narcotic antagonist. The rapid decline of naloxone concentration in the brain found in the animal model, in contrast to that of morphine, could be the basis for its relatively short duration of action.", "contents": "Pharmacokinetics of naloxone in rats and in man: basis for its potency and short duration of action. Using a specific and sensitive radioimmunoassay, naloxone concentrations in the brains and sera of rats were measured at intervals for four hours following iv injection (5 mg/kg). Decrement curves of naloxone were compared with those after iv injection of morphine (5 mg/kg). Serum concentration of naloxone at 5 minutes was 1.45 +/- 0.1 mug/ml (mean +/- SE) and that of morphine was 1.0 +/- 0.08 mug/ml. Their serum half-lives from one to four hours were approximately the same, 30-40 minutes. With naloxone, the brain-serum concentration ratios ranged from 2.7 to 4.6. Concentration of naloxone in the brain declined parallel to that in the serum. However, with morphine the initial brain concentration was approximately one tenth that in the serum (0.096 +/- 0.04 mug/ml). The brain morphine concentration was sustained for one hour, while serum morphine concentrations declined from 1.0 to 0.19 mug/ml during this period. Two minutes after iv injection of naloxone HCl (0.4 mg) in nine healthy volunteers, the serum drug concentration was 0.01 +/- .001 mug/ml. At 5 minutes, 97 per cent of the administered dose was no longer found in the serum, the serum concentration being 0.004 +/- .0003 mug/ml. From 20 minutes to two hours after injection, the calculated mean serum half-life of naloxone was 64 minutes. These results suggest that the rapid penetrance of naloxone into the brain and the high brain-serum concentration ratio contribute to its rapid onset of action and potency as a narcotic antagonist. The rapid decline of naloxone concentration in the brain found in the animal model, in contrast to that of morphine, could be the basis for its relatively short duration of action."} {"id": "PMID:1267206", "title": "Myocardial function and metabolism in the conscious dog and during halothane anesthesia.", "content": "Chronically catheterized dogs were studied awake and during anesthesia with high and low concentrations of halothane to assess the relationship between cardiac function and metabolism. Low concentrations of halothane (0.79 per cent endtidal) increased heart rate and decreased left ventricular stroke volume, stroke work, and dP/dt without producing other hemodynamic changes. However, similar heart rate increases produced by atrial pacing in awake animals increased aortic pressure and cardiac output and decreased left atrial pressure. Consequently, the halothane-induced tachycardia partially compensated for the negative inotropic effect of the halothane. High concentrations of halothane (1.74 per cent endtidal) further increased heart rate and elevated left atrial pressures. Cardiac output, stroke volume, stroke work, aortic pressure, LV dP/dt, myocardial blood flow and oxygen consumption were markedly decreased. Myocardial glucose extraction was also decreased. Myocardial oxygen extraction was unchanged, and lactate extraction rose with both concentrations of halothane. Consequently, the dose-dependent negative inotropic effect of halothane resulted in a decrease in cardiac oxygen demand which was equal to or greater than the decrease in oxygen delivery. Whether the same relationship would be seen in the ischemic heart is yet to be demonstrated.", "contents": "Myocardial function and metabolism in the conscious dog and during halothane anesthesia. Chronically catheterized dogs were studied awake and during anesthesia with high and low concentrations of halothane to assess the relationship between cardiac function and metabolism. Low concentrations of halothane (0.79 per cent endtidal) increased heart rate and decreased left ventricular stroke volume, stroke work, and dP/dt without producing other hemodynamic changes. However, similar heart rate increases produced by atrial pacing in awake animals increased aortic pressure and cardiac output and decreased left atrial pressure. Consequently, the halothane-induced tachycardia partially compensated for the negative inotropic effect of the halothane. High concentrations of halothane (1.74 per cent endtidal) further increased heart rate and elevated left atrial pressures. Cardiac output, stroke volume, stroke work, aortic pressure, LV dP/dt, myocardial blood flow and oxygen consumption were markedly decreased. Myocardial glucose extraction was also decreased. Myocardial oxygen extraction was unchanged, and lactate extraction rose with both concentrations of halothane. Consequently, the dose-dependent negative inotropic effect of halothane resulted in a decrease in cardiac oxygen demand which was equal to or greater than the decrease in oxygen delivery. Whether the same relationship would be seen in the ischemic heart is yet to be demonstrated."} {"id": "PMID:1267207", "title": "Pressure antagonism of barbiturate anesthesia.", "content": "The losses of righting reflex produced by various doses of phenobarbital in mice at 1 atm O2 versus 1 atm O2 plus 102 atm He were determined. The resulting dose-response curve at pressure gave an ED50 that was 64 per cent larger than the ED50 at 1 atm. This increment is essentially the same as that found for gaseous anesthetics under similar test conditions. The quantitative similarity of the results of pressure reversals of barbiturate and inhalational anesthetics suggests that the mechanisms or sites of action of these agents are similar. However, the dose-response curve at 103 atm was steeper than that at 1 atm. This raises an alternative possibility that anesthetics and pressure bear no mechanistic relationship to each other, but rather that pressure produces a generalized central nervous system stimulation that would antagonize any depressant effect.", "contents": "Pressure antagonism of barbiturate anesthesia. The losses of righting reflex produced by various doses of phenobarbital in mice at 1 atm O2 versus 1 atm O2 plus 102 atm He were determined. The resulting dose-response curve at pressure gave an ED50 that was 64 per cent larger than the ED50 at 1 atm. This increment is essentially the same as that found for gaseous anesthetics under similar test conditions. The quantitative similarity of the results of pressure reversals of barbiturate and inhalational anesthetics suggests that the mechanisms or sites of action of these agents are similar. However, the dose-response curve at 103 atm was steeper than that at 1 atm. This raises an alternative possibility that anesthetics and pressure bear no mechanistic relationship to each other, but rather that pressure produces a generalized central nervous system stimulation that would antagonize any depressant effect."} {"id": "PMID:1267209", "title": "Brain-blood partition coefficients of 85Krypton at 37 C and 29.5 C.", "content": "To permit utilization of the Kety-Schmidt technique for measuring cerebral blood flow during hypothermia, the brain-blood partition coefficients for 85krypton at 37 C and 29.5 C were determined in a series of cats. At 37 C the partition coefficient for 85krypton was 1.092 +/- 0.009; it was 0.931 +/- 0.007 (SE) at 29.5 C. These values were significantly different from each other (P less than .001).", "contents": "Brain-blood partition coefficients of 85Krypton at 37 C and 29.5 C. To permit utilization of the Kety-Schmidt technique for measuring cerebral blood flow during hypothermia, the brain-blood partition coefficients for 85krypton at 37 C and 29.5 C were determined in a series of cats. At 37 C the partition coefficient for 85krypton was 1.092 +/- 0.009; it was 0.931 +/- 0.007 (SE) at 29.5 C. These values were significantly different from each other (P less than .001)."} {"id": "PMID:1267210", "title": "Stability of pseudocholinesterase in stored blood.", "content": "No significant change in pseudocholinesterase levels was observed in random specimens of whole blood stored for as long as 30 days. Levels in plasma anticoagulated with heparin or ethylenediaminetetraacetic acid declined only slightly. Therefore, massive transfusions do not contraindicate succinylcholine administration.", "contents": "Stability of pseudocholinesterase in stored blood. No significant change in pseudocholinesterase levels was observed in random specimens of whole blood stored for as long as 30 days. Levels in plasma anticoagulated with heparin or ethylenediaminetetraacetic acid declined only slightly. Therefore, massive transfusions do not contraindicate succinylcholine administration."} {"id": "PMID:1267219", "title": "[The effect of chlordecone (Kepone) on the laboratory colonies of the Pharaoh's ant Monomorium pharanois].", "content": "The control of the Pharaoh's ant Monomorium pharaonis is very difficult because of the social way of life in this insect pest. In regard to the reported good suppressing results of Chlordecone we analyzed the mode of action in this compound at laboratory colonies of the pharaoh's ant. Commercial gel and granular formulations as well as selfmade baits have been tested. The best results showed the granular bait on the basis of ground nut butter, while the effects of all of the others was much weaker. The pure gel, developed for cockroach control, was like the application in drinking water without success. The treatment of the colonies after a starvation period of 60 hours improved all of the effects. Sterility (fertility, fecundity) in the surviving queens was not measurable. For practical control measures the often recommended prebaiting is not at all desirable. The action on the worker ants is good, but the special mode of action based on the selective mortality in the queens and its detailed effects are unknown. Through the early absence of queens in the colonies will be induced in many cases a production of new sexuals, which compensate the success of the poison and allow the colonies to recover. The treatment leads faster to an eradiction if the ET90 to workers mortality reached earlier than that in the queens. Successful control of pharaoh's ant will Chlordecone should be considered with reserve. Nethertheless Chlordecone is in the present situation of pharaoh's ant control one of the best so far known organic-synthetically insecticides.", "contents": "[The effect of chlordecone (Kepone) on the laboratory colonies of the Pharaoh's ant Monomorium pharanois]. The control of the Pharaoh's ant Monomorium pharaonis is very difficult because of the social way of life in this insect pest. In regard to the reported good suppressing results of Chlordecone we analyzed the mode of action in this compound at laboratory colonies of the pharaoh's ant. Commercial gel and granular formulations as well as selfmade baits have been tested. The best results showed the granular bait on the basis of ground nut butter, while the effects of all of the others was much weaker. The pure gel, developed for cockroach control, was like the application in drinking water without success. The treatment of the colonies after a starvation period of 60 hours improved all of the effects. Sterility (fertility, fecundity) in the surviving queens was not measurable. For practical control measures the often recommended prebaiting is not at all desirable. The action on the worker ants is good, but the special mode of action based on the selective mortality in the queens and its detailed effects are unknown. Through the early absence of queens in the colonies will be induced in many cases a production of new sexuals, which compensate the success of the poison and allow the colonies to recover. The treatment leads faster to an eradiction if the ET90 to workers mortality reached earlier than that in the queens. Successful control of pharaoh's ant will Chlordecone should be considered with reserve. Nethertheless Chlordecone is in the present situation of pharaoh's ant control one of the best so far known organic-synthetically insecticides."} {"id": "PMID:1267220", "title": "[Incidence and damages inflicted by simuliid flies in the GDR district of Schwerin].", "content": "Systematic faunal studies in the district Schwerin showed at the present time there are 3 more or less damage-biotopes existing in the districts of Perleberg, Ludwigslust and Parchim; 5 river sources can be considered as potential sources, 5 are temporary and 2 are ephemeral whilst in 3 further areas environmental influences such as effluent impairs the flow of the river and the developmental stages of Simuliidae were not observed.--The following species were found: Boophthora erythrocephala, Wilhelmia salopiensis, Wilhelmia equina, Odagmia ornata, Eusimulium aureum and Eusimulium lundstroemi.--The damage statistics covering the period 1966--1971 showed in the district of Schwerin, due to Simuliid attacks, 38 cattle died, 170 were seriously ill; in 1967 5 horses were seriously ill; in 1971, 3 pigs died and 27 were seriously ill.--The symptoms were manifested by pathological petechiae, scabs and oedema, also by insufficiency of the heart and circulatory system, diminished performance and growth disturbance. In severe cases heart and circulation failure occurred, paresis, coma and death followed.--The real economic significance of the Simuliid attacks rest with its strong and prolonged distrubance in young animals, as well as in pronounced irreparable diminished performance in diseased dairy cattle.", "contents": "[Incidence and damages inflicted by simuliid flies in the GDR district of Schwerin]. Systematic faunal studies in the district Schwerin showed at the present time there are 3 more or less damage-biotopes existing in the districts of Perleberg, Ludwigslust and Parchim; 5 river sources can be considered as potential sources, 5 are temporary and 2 are ephemeral whilst in 3 further areas environmental influences such as effluent impairs the flow of the river and the developmental stages of Simuliidae were not observed.--The following species were found: Boophthora erythrocephala, Wilhelmia salopiensis, Wilhelmia equina, Odagmia ornata, Eusimulium aureum and Eusimulium lundstroemi.--The damage statistics covering the period 1966--1971 showed in the district of Schwerin, due to Simuliid attacks, 38 cattle died, 170 were seriously ill; in 1967 5 horses were seriously ill; in 1971, 3 pigs died and 27 were seriously ill.--The symptoms were manifested by pathological petechiae, scabs and oedema, also by insufficiency of the heart and circulatory system, diminished performance and growth disturbance. In severe cases heart and circulation failure occurred, paresis, coma and death followed.--The real economic significance of the Simuliid attacks rest with its strong and prolonged distrubance in young animals, as well as in pronounced irreparable diminished performance in diseased dairy cattle."} {"id": "PMID:1267221", "title": "[Metacercaria in the invertebrates of the Madras coast].", "content": "In planktonic and benthic invertebrates of the Madras coast, Bay of Bengal, six Metacercariae have been reported. Four species are from planktonic intermediate hosts. They were found in Ctenophora, Leptomedusa and the gastropod Janthina. They belong to the Hemiurate, Fellodistomatidae and Lepocreadiidae. Two species are from benthic molluscs and belong to the family Monorchiidae respectively to the subfamily Halipeginae. We can expect that the adults of three species are not described.", "contents": "[Metacercaria in the invertebrates of the Madras coast]. In planktonic and benthic invertebrates of the Madras coast, Bay of Bengal, six Metacercariae have been reported. Four species are from planktonic intermediate hosts. They were found in Ctenophora, Leptomedusa and the gastropod Janthina. They belong to the Hemiurate, Fellodistomatidae and Lepocreadiidae. Two species are from benthic molluscs and belong to the family Monorchiidae respectively to the subfamily Halipeginae. We can expect that the adults of three species are not described."} {"id": "PMID:1267223", "title": "[Assitrema eichleri gen. et spec. nov., a new trematode species from the Indian Ocean].", "content": "A new trematode Assitrema eichleri gen. et spec. nov. is described. The host is a Macrurid (Cory-phaenoidid) fish. The morphology of this flatworm is very aberrant. Therefore it was necessary to erect a new genus in POCHE family Isoparorchidae.", "contents": "[Assitrema eichleri gen. et spec. nov., a new trematode species from the Indian Ocean]. A new trematode Assitrema eichleri gen. et spec. nov. is described. The host is a Macrurid (Cory-phaenoidid) fish. The morphology of this flatworm is very aberrant. Therefore it was necessary to erect a new genus in POCHE family Isoparorchidae."} {"id": "PMID:1267224", "title": "[Plerocercoid infestation of the Thailand reptiles in the Berlin Zoo].", "content": "Plerocercoids were found under the skin and in the body cavity of Ahaetulla nastua, Boiga multimaculata, Trimeresurus purpureomaculatus, and Varanus dumerilii, imported from Thailand. Starting with these plerocercoids the cestode cycle was experimentally traced in the laboratory (Lueheela = Spirometra sp.). Domestic cat and domestic dog served as definitive hosts, native copepods at first intermediate hosts, native anurans, reptiles, and chicken as second intermediate hosts and paratenic hosts. Fishes and a Rhesus Macque were shown to act as paratenic hosts. The ferret was only suitable as paratenic host but not as definitive host. The adult worm in the definitive host periodically cast off the whole strobila corresponding to a cyclic appearance of eggs in the faeces.", "contents": "[Plerocercoid infestation of the Thailand reptiles in the Berlin Zoo]. Plerocercoids were found under the skin and in the body cavity of Ahaetulla nastua, Boiga multimaculata, Trimeresurus purpureomaculatus, and Varanus dumerilii, imported from Thailand. Starting with these plerocercoids the cestode cycle was experimentally traced in the laboratory (Lueheela = Spirometra sp.). Domestic cat and domestic dog served as definitive hosts, native copepods at first intermediate hosts, native anurans, reptiles, and chicken as second intermediate hosts and paratenic hosts. Fishes and a Rhesus Macque were shown to act as paratenic hosts. The ferret was only suitable as paratenic host but not as definitive host. The adult worm in the definitive host periodically cast off the whole strobila corresponding to a cyclic appearance of eggs in the faeces."} {"id": "PMID:1267229", "title": "The transition from sitting on eggs to sitting on young in ring doves, Streptopelia risoria: squab-egg preferences during the normal cycle.", "content": "Ring doves of both sexes sit on young squabs after hatching in much the same manner as they sit on eggs before hatching, but this study demonstrates that the preferred stimulus varies with the state of the animal. A simultaneous squab--egg choice test was given on days 1, 4, 10, and 13 of incubation and on the day following hatching in normal reproductive cycles of experienced and na\u00efve male and female ring doves. Na\u00efve doves were more likely than experienced doves to choose eggs throughout the cycle (P less than 0-005) and, overall, eggs were more likely to be chosen during early incubation and squabs posthatching (P less than 0-005).", "contents": "The transition from sitting on eggs to sitting on young in ring doves, Streptopelia risoria: squab-egg preferences during the normal cycle. Ring doves of both sexes sit on young squabs after hatching in much the same manner as they sit on eggs before hatching, but this study demonstrates that the preferred stimulus varies with the state of the animal. A simultaneous squab--egg choice test was given on days 1, 4, 10, and 13 of incubation and on the day following hatching in normal reproductive cycles of experienced and na\u00efve male and female ring doves. Na\u00efve doves were more likely than experienced doves to choose eggs throughout the cycle (P less than 0-005) and, overall, eggs were more likely to be chosen during early incubation and squabs posthatching (P less than 0-005)."} {"id": "PMID:1267234", "title": "Fibrinogen-related antigen concentrations of blood serum of normal cows, as measured by the tanned erythrocyte hemagglutination-inhibition immunoassay.", "content": "Serum fibrinogen-related antigen concentration values were determined in normal cows, using a tanned erythrocyte hemagglutination inhibition immunoassay. The geometric mean value for serum fibrinogen-related antigen was 6.60 mug/ml. The upper and lower 95% prediction limits for the 38 cows tested were 12.76 and 3.42 mug/ml, respectively.", "contents": "Fibrinogen-related antigen concentrations of blood serum of normal cows, as measured by the tanned erythrocyte hemagglutination-inhibition immunoassay. Serum fibrinogen-related antigen concentration values were determined in normal cows, using a tanned erythrocyte hemagglutination inhibition immunoassay. The geometric mean value for serum fibrinogen-related antigen was 6.60 mug/ml. The upper and lower 95% prediction limits for the 38 cows tested were 12.76 and 3.42 mug/ml, respectively."} {"id": "PMID:1267235", "title": "Electrocardiographic changes after induced hypercalcemia and hypocalcemia in cattle: reversal of the induced arrhythmia with atropine.", "content": "The relationship between the Q-oTc interval of the ventricular complex of calves and cows and the total calcium and calcium ion activity was quantitated. A proportional relationship of the Q-oTc existed between total calcium concentrations in the plasma of 5.5 to 8.2 mEq/L and calcium ion activities of 0.75 to 3.2 mEq/L. At higher calcium concentrations, the relationship was curvilinear and very variable. The Q-oTc interval was lengthened during induced hypocalcemic states and shortened during hypercalcemic states. Hypercalcemia seemed to decrease atrial activity and increase ventricular activity, as evidenced by the appearance of bradycardia, sinus arrest, and ectopic ventricular beats. Vagal activity seemed altered by the changes in plasma calcium concentrations and involved in the production of the arrhythmia, because atropine could abolish the arrhythmia created by the infusion of the calcium solutions.", "contents": "Electrocardiographic changes after induced hypercalcemia and hypocalcemia in cattle: reversal of the induced arrhythmia with atropine. The relationship between the Q-oTc interval of the ventricular complex of calves and cows and the total calcium and calcium ion activity was quantitated. A proportional relationship of the Q-oTc existed between total calcium concentrations in the plasma of 5.5 to 8.2 mEq/L and calcium ion activities of 0.75 to 3.2 mEq/L. At higher calcium concentrations, the relationship was curvilinear and very variable. The Q-oTc interval was lengthened during induced hypocalcemic states and shortened during hypercalcemic states. Hypercalcemia seemed to decrease atrial activity and increase ventricular activity, as evidenced by the appearance of bradycardia, sinus arrest, and ectopic ventricular beats. Vagal activity seemed altered by the changes in plasma calcium concentrations and involved in the production of the arrhythmia, because atropine could abolish the arrhythmia created by the infusion of the calcium solutions."} {"id": "PMID:1267236", "title": "Sequential sterile autolysis in the ovine fetus: macroscopic changes.", "content": "Sterile intrauterine autolysis was experimentally produced in 28 ovine fetuses in the last 3rd of gestation by umbilical artery ligation. The fetuses were retrieved by cesarean section after periods of sterile intrauterine autolysis ranging from 0.5 to 168 hours. The following autolytic changes, frequently reported as significant lesions in infectious abortions in cattle and sheep, were observed: subcutaneous blood-tinged gelatinous edema, blood-tinged fluid in the serous cavities, renal cortical softening, uniform reddish brown tissues, hepatic friability and mottling, and cloudy yellow to cloudy red abomasal contents. The appearance of these and other autolytic changes corresponded to sterile sequential autolytic changes reported in the rabbit fetus and used to determine duration of retention of stillborn infants and are of comparative biomedical significance. The sequential autolytic changes may be used as an index to duration of retention after death of a ruminant fetus and provide a basis for reappraising various infective abortifacients common to ruminants by allowing separation of specific lesions from strictly autolytic changes.", "contents": "Sequential sterile autolysis in the ovine fetus: macroscopic changes. Sterile intrauterine autolysis was experimentally produced in 28 ovine fetuses in the last 3rd of gestation by umbilical artery ligation. The fetuses were retrieved by cesarean section after periods of sterile intrauterine autolysis ranging from 0.5 to 168 hours. The following autolytic changes, frequently reported as significant lesions in infectious abortions in cattle and sheep, were observed: subcutaneous blood-tinged gelatinous edema, blood-tinged fluid in the serous cavities, renal cortical softening, uniform reddish brown tissues, hepatic friability and mottling, and cloudy yellow to cloudy red abomasal contents. The appearance of these and other autolytic changes corresponded to sterile sequential autolytic changes reported in the rabbit fetus and used to determine duration of retention of stillborn infants and are of comparative biomedical significance. The sequential autolytic changes may be used as an index to duration of retention after death of a ruminant fetus and provide a basis for reappraising various infective abortifacients common to ruminants by allowing separation of specific lesions from strictly autolytic changes."} {"id": "PMID:1267237", "title": "Ovine campylobacterosis: preliminary studies of the efficacy of the in vitro serum bactericidal test as an assay for the potency of Campylobacter (Vibrio) fetus subsp intestinalis bacterins.", "content": "An in vitro serum bactericidal test was developed to assess the efficacy of Campylobacter fetus bacterins. Four experimental monovalent bacterins (either serotype C or A-2) and 2 commercial bivalent bacterins (a \"suspect\" and an \"efficacious\" bacterin) with aluminum hydroxide adjuvant were administered to sheep and rabbits from which antiserums were then prepared. The different vaccines were evaluated by comparing the in vitro bactericidal activity of the sheep and rabbit antiserums. Results of the in vitro tests were compared to the protection induced in vaccinated ewes which were orally exposed to C fetus. The sheep and the rabbit antiserums after they were heated at 56 C for 30 minutes were unable to exert a killing effect on C fetus cells. Addition of a fresh homologous complement source to the heated antiserums was necessary to demonstrate the in vitro bactericidal capacity. In the comparison of the suspect and the efficacious commercial bacterins, which both reportedly contain serotype C cells, there was a statistically significant difference in bactericidal activities for serotype C cells of antiserums from sheep 14 days after the 2nd vaccination. There was a corresponding significant difference in the antiserums from rabbits 14 days after the 2nd vaccination. Proportionally, more abortions and stillbirths were observed in the ewes vaccinated with the suspect bacterin and then orally exposed to C fetus-serotype C cells than in those vaccinated with the efficacious bacterin. The results indicated that the ability of vaccinated sheep to overcome infection is reflected in the in vitro bactericidal capacity of antiserum from the animal. Since 89% of the variation in sheep antiserums from 14 days after 2nd vaccination can be accounted for by rabbit antiserums from 14 days after 2nd vaccination, the in vitro bactericidal capacity of rabbit antiserums probably provides a reliable index of the protective effect of bacterins containing serotype C for ewes exposed to the homologous serotype.", "contents": "Ovine campylobacterosis: preliminary studies of the efficacy of the in vitro serum bactericidal test as an assay for the potency of Campylobacter (Vibrio) fetus subsp intestinalis bacterins. An in vitro serum bactericidal test was developed to assess the efficacy of Campylobacter fetus bacterins. Four experimental monovalent bacterins (either serotype C or A-2) and 2 commercial bivalent bacterins (a \"suspect\" and an \"efficacious\" bacterin) with aluminum hydroxide adjuvant were administered to sheep and rabbits from which antiserums were then prepared. The different vaccines were evaluated by comparing the in vitro bactericidal activity of the sheep and rabbit antiserums. Results of the in vitro tests were compared to the protection induced in vaccinated ewes which were orally exposed to C fetus. The sheep and the rabbit antiserums after they were heated at 56 C for 30 minutes were unable to exert a killing effect on C fetus cells. Addition of a fresh homologous complement source to the heated antiserums was necessary to demonstrate the in vitro bactericidal capacity. In the comparison of the suspect and the efficacious commercial bacterins, which both reportedly contain serotype C cells, there was a statistically significant difference in bactericidal activities for serotype C cells of antiserums from sheep 14 days after the 2nd vaccination. There was a corresponding significant difference in the antiserums from rabbits 14 days after the 2nd vaccination. Proportionally, more abortions and stillbirths were observed in the ewes vaccinated with the suspect bacterin and then orally exposed to C fetus-serotype C cells than in those vaccinated with the efficacious bacterin. The results indicated that the ability of vaccinated sheep to overcome infection is reflected in the in vitro bactericidal capacity of antiserum from the animal. Since 89% of the variation in sheep antiserums from 14 days after 2nd vaccination can be accounted for by rabbit antiserums from 14 days after 2nd vaccination, the in vitro bactericidal capacity of rabbit antiserums probably provides a reliable index of the protective effect of bacterins containing serotype C for ewes exposed to the homologous serotype."} {"id": "PMID:1267238", "title": "Digital computer analysis of the QRS complex of the dog, using the McFee axial system.", "content": "Digital computer analysis of the canine orthogonal electrocardiogram was performed on 30 clinically normal dogs, as recorded by the McFee axial system. The spatiogeometric properties calculated included: time duration of QRS, time integral of QRS, eigenvalues of the QRSsE loop, eigenvectors, spatial magnitude, and spatial velocity. Electrocardiograms were recorded by FM tape recorder, analogue-to-digital conversion performed, and the analytical procedure utilized the IBM 360/75 digital computer controlled by a FORTRAN G source program. The QRS complex and spatial values were qualitatively similar to those in other reports.", "contents": "Digital computer analysis of the QRS complex of the dog, using the McFee axial system. Digital computer analysis of the canine orthogonal electrocardiogram was performed on 30 clinically normal dogs, as recorded by the McFee axial system. The spatiogeometric properties calculated included: time duration of QRS, time integral of QRS, eigenvalues of the QRSsE loop, eigenvectors, spatial magnitude, and spatial velocity. Electrocardiograms were recorded by FM tape recorder, analogue-to-digital conversion performed, and the analytical procedure utilized the IBM 360/75 digital computer controlled by a FORTRAN G source program. The QRS complex and spatial values were qualitatively similar to those in other reports."} {"id": "PMID:1267239", "title": "Controlled evaluation of fenbendazole as a bovine anthelmintic.", "content": "Calves experimentally infected with Haemonchus, Ostertagia, and Cooperia, and to lesser degrees with Trichostrongylus, Oesophagostomum, Nematodirus, and Bunostomum were used in a controlled experiment to record the anthelmintic efficacy of a benzimidazole compound methyl 5-(phenylthio)-2-benzimidazolecarbamate at dosage levels of 3.5, 5, and 7.5 mg/kg bodyweight. With the 3 dosages, reductions of Haemonchus were 96.7, 99.2, and 99.8%; of Ostertagia, 97.2, 97.2, and 99.5%; and of Cooperia, 99.9, 99.9, and 99.9%. Pronounced reductions were also recorded for Trichostrongylus, Nematodirus, Oesophagostomum, Trichuris, and Capillaria, but these populations were too numerically small or too unevenly distributed within the control groups to be given much emphasis. The experimental parasitic populations which developed in the 10 control calves amounted to 91, 763 worms (total).", "contents": "Controlled evaluation of fenbendazole as a bovine anthelmintic. Calves experimentally infected with Haemonchus, Ostertagia, and Cooperia, and to lesser degrees with Trichostrongylus, Oesophagostomum, Nematodirus, and Bunostomum were used in a controlled experiment to record the anthelmintic efficacy of a benzimidazole compound methyl 5-(phenylthio)-2-benzimidazolecarbamate at dosage levels of 3.5, 5, and 7.5 mg/kg bodyweight. With the 3 dosages, reductions of Haemonchus were 96.7, 99.2, and 99.8%; of Ostertagia, 97.2, 97.2, and 99.5%; and of Cooperia, 99.9, 99.9, and 99.9%. Pronounced reductions were also recorded for Trichostrongylus, Nematodirus, Oesophagostomum, Trichuris, and Capillaria, but these populations were too numerically small or too unevenly distributed within the control groups to be given much emphasis. The experimental parasitic populations which developed in the 10 control calves amounted to 91, 763 worms (total)."} {"id": "PMID:1267240", "title": "Ultrastructure of blood platelets in cattle with East Coast fever.", "content": "The sequence of ultrastructural changes of bovine platelets during the fatal course of East Coast fever was swelling; formation of vacuoles, pseudopodia, and indentations; then thrombocytorrhexis and degranulation; and finally, thrombocytolysis. These changes led to thrombocytopenia and release of serotonin, resulting in petechiations and pulmonary edema.", "contents": "Ultrastructure of blood platelets in cattle with East Coast fever. The sequence of ultrastructural changes of bovine platelets during the fatal course of East Coast fever was swelling; formation of vacuoles, pseudopodia, and indentations; then thrombocytorrhexis and degranulation; and finally, thrombocytolysis. These changes led to thrombocytopenia and release of serotonin, resulting in petechiations and pulmonary edema."} {"id": "PMID:1267241", "title": "Effect of nematode parasite infection on the performance of stocker cattle at high stocking rates on coastal bermudagrass pastures.", "content": "Studies were conducted during the summer of 2 successive years (1971 and 1972) to determine the effects of gastrointestinal nematode parasitism on performance failure of stocker beef steers grazed at high stocking rates on Coastal bermudagrass pastures. During each of the 2 years, 3 groups of steers were rotated at 7- to 10-day intervals on sets of three 1.63-ha pastures from mid-May to late October. (Each group was maintained on a given set of pastures.) In the 1971 program, from mid-May to early August (phase 1) each group consisted of 48 steers for a stocking rate of 29.6 steers/ha. From early August to late October (phase 2) the number of steers per group was reduced to 36 (stocking rate of 22.2 steers/ha) to improve the plane of nutrition. In the 1972 program, 2 groups were stocked at 48 steers per group (29.6 steers/ha) and a 3rd group was temporarily stocked with 58 steers (10 additional steers) to provide 2 animals each month for necropsy evaluation of worm burdens. With exception of the monthly removal of 2 steers from the 3rd group, the stocking rate in 1972 remained intact for the entire grazing season. In 1971, the 3 groups (groups 1, 2, and 3) were treated with thiabendazole (2 doses, 16 days between doses) before grazing. Parasite burdens and levels of pasture contamination were low initially and body weight gains were good during the 1st 3 months of grazing (phase 1). In the 2nd half (phase 2) of the grazing program, 1 group of steers given free-choice supplemental feed (1% of body weight/steer each day) and treated with anthelmintic (thiabendazole; 2 doses, 18 days between doses, during August) and another group, given supplemental feed only, had significantly better weight gains than did the 3rd group, not given supplemental feed nor treated with anthelmintic. There was no weight gain advantage derived from the reduced stocking rate in phase 2. Tracer calves, which were allowed to graze on pastures, developed an increased level of infection after August. Fecal egg counts in the principal steers and recovery of infective larvae from pasture paralleled the infection level in tracer calves. Necropsy evaluation of steers from groups 1, 2, and 3 at the end of the 1971 program indicated a similarity in total worm counts, but in the group not given supplemental feed nor treated with anthelmintic there was more generalized inflammation and a greater number of lesions in the abomasum (Ostertagia) and the caudal portion of the intestine (Oesophagostomum). Steers in the 3rd group also were in poorer condition. Initial worm burdens in the 3 steer groups (groups 4, 5, and 6) were low at the start of the 1972 program. One group was given freechoice supplemental feed (0.5% of body weight/steer each day) and treated with anthelmintics (thiabendazole in the 1st dose, levamisole in the 2nd dose, 12 days between doses, in May and August) and another group was given supplemental feed throughout the summer; the 3rd group was treated with anthelmintics (in May and August)...", "contents": "Effect of nematode parasite infection on the performance of stocker cattle at high stocking rates on coastal bermudagrass pastures. Studies were conducted during the summer of 2 successive years (1971 and 1972) to determine the effects of gastrointestinal nematode parasitism on performance failure of stocker beef steers grazed at high stocking rates on Coastal bermudagrass pastures. During each of the 2 years, 3 groups of steers were rotated at 7- to 10-day intervals on sets of three 1.63-ha pastures from mid-May to late October. (Each group was maintained on a given set of pastures.) In the 1971 program, from mid-May to early August (phase 1) each group consisted of 48 steers for a stocking rate of 29.6 steers/ha. From early August to late October (phase 2) the number of steers per group was reduced to 36 (stocking rate of 22.2 steers/ha) to improve the plane of nutrition. In the 1972 program, 2 groups were stocked at 48 steers per group (29.6 steers/ha) and a 3rd group was temporarily stocked with 58 steers (10 additional steers) to provide 2 animals each month for necropsy evaluation of worm burdens. With exception of the monthly removal of 2 steers from the 3rd group, the stocking rate in 1972 remained intact for the entire grazing season. In 1971, the 3 groups (groups 1, 2, and 3) were treated with thiabendazole (2 doses, 16 days between doses) before grazing. Parasite burdens and levels of pasture contamination were low initially and body weight gains were good during the 1st 3 months of grazing (phase 1). In the 2nd half (phase 2) of the grazing program, 1 group of steers given free-choice supplemental feed (1% of body weight/steer each day) and treated with anthelmintic (thiabendazole; 2 doses, 18 days between doses, during August) and another group, given supplemental feed only, had significantly better weight gains than did the 3rd group, not given supplemental feed nor treated with anthelmintic. There was no weight gain advantage derived from the reduced stocking rate in phase 2. Tracer calves, which were allowed to graze on pastures, developed an increased level of infection after August. Fecal egg counts in the principal steers and recovery of infective larvae from pasture paralleled the infection level in tracer calves. Necropsy evaluation of steers from groups 1, 2, and 3 at the end of the 1971 program indicated a similarity in total worm counts, but in the group not given supplemental feed nor treated with anthelmintic there was more generalized inflammation and a greater number of lesions in the abomasum (Ostertagia) and the caudal portion of the intestine (Oesophagostomum). Steers in the 3rd group also were in poorer condition. Initial worm burdens in the 3 steer groups (groups 4, 5, and 6) were low at the start of the 1972 program. One group was given freechoice supplemental feed (0.5% of body weight/steer each day) and treated with anthelmintics (thiabendazole in the 1st dose, levamisole in the 2nd dose, 12 days between doses, in May and August) and another group was given supplemental feed throughout the summer; the 3rd group was treated with anthelmintics (in May and August)..."} {"id": "PMID:1267242", "title": "Serum testosterone and estrogen concentrations in the Holstein-Friesian bull after successive ejaculations.", "content": "The testosterone and estrogen concentrations in venous serum of 4 mature Holstein-Friesian bulls were determined by radioimmunoassay before and after each of 3 consecutive semen collections taken at 1-hour intervals. The hormonal concentrations were highly variable for the 2 steroids, but uniform in their patterns after the bulls had ejaculated. After the 3rd semen collection, marked changes in hormonal concentrations did not occur.", "contents": "Serum testosterone and estrogen concentrations in the Holstein-Friesian bull after successive ejaculations. The testosterone and estrogen concentrations in venous serum of 4 mature Holstein-Friesian bulls were determined by radioimmunoassay before and after each of 3 consecutive semen collections taken at 1-hour intervals. The hormonal concentrations were highly variable for the 2 steroids, but uniform in their patterns after the bulls had ejaculated. After the 3rd semen collection, marked changes in hormonal concentrations did not occur."} {"id": "PMID:1267243", "title": "Critical tests with oxibendazole against gastrointestinal parasites of ponies.", "content": "Twenty ponies were allotted to 4 groups of 5 ponies each, and oxibendazole was orally administered at dose levels of 5, 10, 15, and 20 mg/kg. In the 3 groups of ponies given the largest doses, efficacy against 3 species of Strongylus was between 92 and 100% and that against small strongylids of the genera Cyathostomum, Cylicocyclus, Cylicodontophorus, and Cylicostephanus was more than 99%. All adults and 95 to 100% of larvae of the pinworm Oxyuris equi were removed. In the group of ponies given 5 mg/kg, 86 to 100% of the large strongylids and 84 to 100% of the small strongylids were removed, as were all larval and adult pinworms. Trichostrongylus axei was found only in 4 of the 5 ponies given 5 mg/kg; results were encouraging, but not consistent. Almost all of the Parascaris equorum were found in this group of ponies; no anthelmintic activity was detected at this dose level. Oxibendazole removed approximately 99% of small strongylid 4th-stage larvae. No efficacy against the larval stages of Gasterophilus intestinalis and against Habronema spp and Setaria equina was observed.", "contents": "Critical tests with oxibendazole against gastrointestinal parasites of ponies. Twenty ponies were allotted to 4 groups of 5 ponies each, and oxibendazole was orally administered at dose levels of 5, 10, 15, and 20 mg/kg. In the 3 groups of ponies given the largest doses, efficacy against 3 species of Strongylus was between 92 and 100% and that against small strongylids of the genera Cyathostomum, Cylicocyclus, Cylicodontophorus, and Cylicostephanus was more than 99%. All adults and 95 to 100% of larvae of the pinworm Oxyuris equi were removed. In the group of ponies given 5 mg/kg, 86 to 100% of the large strongylids and 84 to 100% of the small strongylids were removed, as were all larval and adult pinworms. Trichostrongylus axei was found only in 4 of the 5 ponies given 5 mg/kg; results were encouraging, but not consistent. Almost all of the Parascaris equorum were found in this group of ponies; no anthelmintic activity was detected at this dose level. Oxibendazole removed approximately 99% of small strongylid 4th-stage larvae. No efficacy against the larval stages of Gasterophilus intestinalis and against Habronema spp and Setaria equina was observed."} {"id": "PMID:1267250", "title": "Effect of helium on maximal expiratory flow in patients with asthma before and during induced bronchoconstriction.", "content": "The effect of breathing helium on maximal expiratory flow at 50 per cent of vital capacity (V50) was studied in 27 patients with asthma during remission and during induced bronchoconstriction. Nine patients gave a history of asthma induced by exercise; two had asthma due to timothy pollen allergy, and the remaining 16 had asthma due to exposure to western red cedar. Bronchoconstriction was induced by exercise in 10 patients, timothy pollen in 4 patients, methacholine in 4 patients, and red cedar in 16 patients. During remission, the increase in V50 with helium (deltaV50He) was greater than 20 per cent in 22 patients who were classified as responders; deltaV50He was less than 20 per cent in the remaining 5 patients, who were classified as nonresponders. There was a significant correlation between the severity of airway obstruction as measured by V50 and the response to helium, both during remission and during induced bronchoconstriction; however, there was no correlation between helium response and specific airway conductance. In general, patients who were responders during remission remained responders during induced bronchoconstriction, and nonresponders remained nonresponders, regardless of the method of challenge or the type of reaction (immediate verus late). There were a few exceptions in which a responder became a nonresponder during severe bronchoconstriction. The results of this study suggest that in most patients with asthma, the site of airway obstruction is likely to be in the large airways and, in most cases, remains constant in an individual asthmatic; however, an asthmatic who is a helium responder may become a nonresponder during severe bronchoconstriction.", "contents": "Effect of helium on maximal expiratory flow in patients with asthma before and during induced bronchoconstriction. The effect of breathing helium on maximal expiratory flow at 50 per cent of vital capacity (V50) was studied in 27 patients with asthma during remission and during induced bronchoconstriction. Nine patients gave a history of asthma induced by exercise; two had asthma due to timothy pollen allergy, and the remaining 16 had asthma due to exposure to western red cedar. Bronchoconstriction was induced by exercise in 10 patients, timothy pollen in 4 patients, methacholine in 4 patients, and red cedar in 16 patients. During remission, the increase in V50 with helium (deltaV50He) was greater than 20 per cent in 22 patients who were classified as responders; deltaV50He was less than 20 per cent in the remaining 5 patients, who were classified as nonresponders. There was a significant correlation between the severity of airway obstruction as measured by V50 and the response to helium, both during remission and during induced bronchoconstriction; however, there was no correlation between helium response and specific airway conductance. In general, patients who were responders during remission remained responders during induced bronchoconstriction, and nonresponders remained nonresponders, regardless of the method of challenge or the type of reaction (immediate verus late). There were a few exceptions in which a responder became a nonresponder during severe bronchoconstriction. The results of this study suggest that in most patients with asthma, the site of airway obstruction is likely to be in the large airways and, in most cases, remains constant in an individual asthmatic; however, an asthmatic who is a helium responder may become a nonresponder during severe bronchoconstriction."} {"id": "PMID:1267251", "title": "The value of precipitating antibodies in screening for hypersensitivity pneumonitis.", "content": "To evaluate the usefulness of precipitin tests as a screening method to detect hypersensitivity pneumonitis, we compared persons with precipitins to organic antigens with precipitin-negative subjects from the same population of 1,072 office workers participating in a health survey examination. Thirty-three of the 53 persons with preciptins to Micropolyspora faeni, Thermoactinomyces vulgaris, T. candidus, pigeon serum, aspergillus, alternaria, pullularia, penicillium, cephalosporium, trichoderma, and phoma were matched according to age, sex, height, and smoking habits with precipitin-negative subjects. The subjects completed a self-administered standard questionnaire, they were interviewed and examined, chest radiograms were taken, and pulmonary functions were evaluated at rest and during mild and moderate exercise. No significant differences were found between the 2 populations in any of the pulmonary function measurements. In addition, clinical and radiologic evidence failed to distinguish between the 2 groups. No cases of hypersensitivity pneumonitis were found. In this population, precipitins had no apparent relationship to long disease. The frequency of precipitins was considerably higher than the frequency of hypersensitivity pneumonitis. We concluded that the detection of hypersensitivity pneumonitis in population surveys attempting to establish prevalence of the disease cannot be accomplished by the simple analysis of serum precipitating antibodies but requires, in addition, a more complex analysis of historical, radiologic, and immunologic data.", "contents": "The value of precipitating antibodies in screening for hypersensitivity pneumonitis. To evaluate the usefulness of precipitin tests as a screening method to detect hypersensitivity pneumonitis, we compared persons with precipitins to organic antigens with precipitin-negative subjects from the same population of 1,072 office workers participating in a health survey examination. Thirty-three of the 53 persons with preciptins to Micropolyspora faeni, Thermoactinomyces vulgaris, T. candidus, pigeon serum, aspergillus, alternaria, pullularia, penicillium, cephalosporium, trichoderma, and phoma were matched according to age, sex, height, and smoking habits with precipitin-negative subjects. The subjects completed a self-administered standard questionnaire, they were interviewed and examined, chest radiograms were taken, and pulmonary functions were evaluated at rest and during mild and moderate exercise. No significant differences were found between the 2 populations in any of the pulmonary function measurements. In addition, clinical and radiologic evidence failed to distinguish between the 2 groups. No cases of hypersensitivity pneumonitis were found. In this population, precipitins had no apparent relationship to long disease. The frequency of precipitins was considerably higher than the frequency of hypersensitivity pneumonitis. We concluded that the detection of hypersensitivity pneumonitis in population surveys attempting to establish prevalence of the disease cannot be accomplished by the simple analysis of serum precipitating antibodies but requires, in addition, a more complex analysis of historical, radiologic, and immunologic data."} {"id": "PMID:1267252", "title": "Role of infection in chronic bronchitis.", "content": "Twenty-five patients with chronic bronchitis were studied intensively from 1968 to 1972. Viral, bacteriologic, mycologic, and mycoplasmal studies, both serologic and cultural, were carried out in an attempt to determine the role these agents play in exacerbations. All of the usual viral agents associated with exacerbations and 2 members of the coronavirus group, 229E and OC43, were detected. One third (33.6 per cent) of the 116 exacerbations observed could be related to viral infection or Mycoplasma pneumoniae (1 exacerbation). Viral infection was also noted to occur during periods of remission but was more commonly associated with periods of exacerbation(P less than 0.001). No interrelationship between viral and bacterial infection was apparent and neither Streptococcus pneumoniae nor Haemophilus influenzae was present more frequently in the sputum of patients in exacerbation. However, the number of S. pneumoniae organisms present in the sputum was significantly greater (P=0.04) during exacerbation than during remission and their presence was significatnly correlated with increases sputum purulence (P LESS THAN 0.01). This was not true of H. influenzae. Ampicillin was effective in clearing the sputum of S. pneumoniae but not of H. influenzae; the reverse was true of tetracycline.", "contents": "Role of infection in chronic bronchitis. Twenty-five patients with chronic bronchitis were studied intensively from 1968 to 1972. Viral, bacteriologic, mycologic, and mycoplasmal studies, both serologic and cultural, were carried out in an attempt to determine the role these agents play in exacerbations. All of the usual viral agents associated with exacerbations and 2 members of the coronavirus group, 229E and OC43, were detected. One third (33.6 per cent) of the 116 exacerbations observed could be related to viral infection or Mycoplasma pneumoniae (1 exacerbation). Viral infection was also noted to occur during periods of remission but was more commonly associated with periods of exacerbation(P less than 0.001). No interrelationship between viral and bacterial infection was apparent and neither Streptococcus pneumoniae nor Haemophilus influenzae was present more frequently in the sputum of patients in exacerbation. However, the number of S. pneumoniae organisms present in the sputum was significantly greater (P=0.04) during exacerbation than during remission and their presence was significatnly correlated with increases sputum purulence (P LESS THAN 0.01). This was not true of H. influenzae. Ampicillin was effective in clearing the sputum of S. pneumoniae but not of H. influenzae; the reverse was true of tetracycline."} {"id": "PMID:1267253", "title": "Chronic nonspecific respiratory disease in Berlin, New Hampshire, 1967 to 1973. A further follow-up study.", "content": "The 1967 sample of Berlin, New Hampshire was resurveyed in 1973 by means of a standard questionnaire on respiratory symptoms and by simple tests of pulmonary function. Measurements of the levels of air pollution showed a decrease in the number of suspended particulates and an increase in the concentration of sulfation. These values were close to the Federal Primary Standard. No differences in respiratory symptoms, prevalences of chronic, nonspecific respiratory disease, or pulmonary function were detected. Within the limitations of this study, we concluded that the Federal Primary Standards for sulfur dioxide and total suspended particulates are probably adequate to protect the public.", "contents": "Chronic nonspecific respiratory disease in Berlin, New Hampshire, 1967 to 1973. A further follow-up study. The 1967 sample of Berlin, New Hampshire was resurveyed in 1973 by means of a standard questionnaire on respiratory symptoms and by simple tests of pulmonary function. Measurements of the levels of air pollution showed a decrease in the number of suspended particulates and an increase in the concentration of sulfation. These values were close to the Federal Primary Standard. No differences in respiratory symptoms, prevalences of chronic, nonspecific respiratory disease, or pulmonary function were detected. Within the limitations of this study, we concluded that the Federal Primary Standards for sulfur dioxide and total suspended particulates are probably adequate to protect the public."} {"id": "PMID:1267254", "title": "Use and withdrawal of amantadine chemoprophylaxis during epidemic influenza A.", "content": "A controlled investigation of chemoprophylaxis with amantadine hydrochloride during an epidemic of influenza A was performed in nonimmune students. Illness was significantly decreased and serologic evidence of infection reduced by treatment. During the post-treatment period, while influenza was still prevalent, an accelerated rate of infection occurred among persons previously protected by chemotherapy. When used, chemoprophylaxis should be continued until influenza is no longer prevalent or, preferably, should be combined with vaccine administration to ensure protection after treatment.", "contents": "Use and withdrawal of amantadine chemoprophylaxis during epidemic influenza A. A controlled investigation of chemoprophylaxis with amantadine hydrochloride during an epidemic of influenza A was performed in nonimmune students. Illness was significantly decreased and serologic evidence of infection reduced by treatment. During the post-treatment period, while influenza was still prevalent, an accelerated rate of infection occurred among persons previously protected by chemotherapy. When used, chemoprophylaxis should be continued until influenza is no longer prevalent or, preferably, should be combined with vaccine administration to ensure protection after treatment."} {"id": "PMID:1267255", "title": "The effect of betamethasone on pressure-volume characteristics of nonfetal rat lungs.", "content": "Betamethasone was administered to rats for 28 days, and body weight, lung weight, and descending pressure-volume relations were measured in their excised lungs. In rats treated with corticosteroid, lung and body weights increased less rapidly than in control rats, but the ratio of lung wet weight to body weight and the per cent dry weight remained the same in both groups. The absolute lung volume was significantly greater at each pressure in the control rats; but when expressed per lung weight, the lungs of rats treated with corticosteroid held more air. When corrected for lung size, the only difference in the lung pressure-volume curves between groups existed at transpulmonary pressures of 0 and 5 cm H2O, where the lungs of the rats treated with betamethasone contained more volume, whether inflated with air or with saline. We concluded that betamethasone administered to nonfetal rats has little influence on the lung's pressure-volume characteristics, which cannot be ascribed to differences in lung size.", "contents": "The effect of betamethasone on pressure-volume characteristics of nonfetal rat lungs. Betamethasone was administered to rats for 28 days, and body weight, lung weight, and descending pressure-volume relations were measured in their excised lungs. In rats treated with corticosteroid, lung and body weights increased less rapidly than in control rats, but the ratio of lung wet weight to body weight and the per cent dry weight remained the same in both groups. The absolute lung volume was significantly greater at each pressure in the control rats; but when expressed per lung weight, the lungs of rats treated with corticosteroid held more air. When corrected for lung size, the only difference in the lung pressure-volume curves between groups existed at transpulmonary pressures of 0 and 5 cm H2O, where the lungs of the rats treated with betamethasone contained more volume, whether inflated with air or with saline. We concluded that betamethasone administered to nonfetal rats has little influence on the lung's pressure-volume characteristics, which cannot be ascribed to differences in lung size."} {"id": "PMID:1267256", "title": "Ventilatory response to carbon dioxide in young athletes: a family study.", "content": "Ventilatory response to carbon dioxide (deltaVE/deltaPCO2) was measured in 23 teenage swimmers chosen by their coach for their potential for future athletic success. Siblings and parents of these swimmers were also studied. We found a strong relation between siblings' de;taVE/DELTAPCO2, whether or not they were swimmers (r=0.71, P less than 0.01). A weaker relationship was found between mother's and children's deltaVE/DELTAPCO2 (r==0.39, P less than 0.01). No association was found between swimming training and deltaVE/deltaPCO2. One swimmer 12 years of age had an extremely low deltaVE/PCO2 (0.42 liter per min per mm Hg) She was the only swimmer among these 23 potential champions to achieve international success in endurance events in the 2 years after the study. We concluded that family factors are important determinants of a subject's deltaVE/PCO2 and suggest that measurement of this aspect of chemical drive to breathing in young athletes may help identify those most likely to succeed in endurance events.", "contents": "Ventilatory response to carbon dioxide in young athletes: a family study. Ventilatory response to carbon dioxide (deltaVE/deltaPCO2) was measured in 23 teenage swimmers chosen by their coach for their potential for future athletic success. Siblings and parents of these swimmers were also studied. We found a strong relation between siblings' de;taVE/DELTAPCO2, whether or not they were swimmers (r=0.71, P less than 0.01). A weaker relationship was found between mother's and children's deltaVE/DELTAPCO2 (r==0.39, P less than 0.01). No association was found between swimming training and deltaVE/deltaPCO2. One swimmer 12 years of age had an extremely low deltaVE/PCO2 (0.42 liter per min per mm Hg) She was the only swimmer among these 23 potential champions to achieve international success in endurance events in the 2 years after the study. We concluded that family factors are important determinants of a subject's deltaVE/PCO2 and suggest that measurement of this aspect of chemical drive to breathing in young athletes may help identify those most likely to succeed in endurance events."} {"id": "PMID:1267257", "title": "Acute hypersensitivity pneumonitis in the rabbit. I. An animal model with horseradish peroxidase as antigen.", "content": "An experimental model of acute hypersensitivity pneumonitis was developed in rabbits using horseradish peroxidase as antigen. The lesion, produced by aerosol challenge with horseradish peroxidase 21 days after a single parenteral immunization with horseradish peroxidase and complete Freund adjuvant, was characterized by diffuse infiltration of respiratory bronchioles and of alveolar ducts and walls with approxomately equal numbers of mononuclear cells (lymphocytes and macrophages) and polymorphonuclear cells. This lesion, which was specific for the antigen, was distinct from the variable granulomatous component that was directly attributable to the use of complete Freund adjubant. Development of the lesion did not correlate with the humoral immune response, as indicated by antigen-binding, precipitin, and homologous passive cutaneous anaphylaxis assays, by negative serum transfer studies, by lack of correlation with immediate and intermediate Arthuslike) skin reactivity, by absence of electron microscopic and immunofluorescent evidence for immune complex processes, and by lack of evidence for complement activation. Development of the lesion did correlate with delayed (12- to 48-hour) skin reactivity, although rigid identification of cell-mediated immunity was not possible on histologic examination.", "contents": "Acute hypersensitivity pneumonitis in the rabbit. I. An animal model with horseradish peroxidase as antigen. An experimental model of acute hypersensitivity pneumonitis was developed in rabbits using horseradish peroxidase as antigen. The lesion, produced by aerosol challenge with horseradish peroxidase 21 days after a single parenteral immunization with horseradish peroxidase and complete Freund adjuvant, was characterized by diffuse infiltration of respiratory bronchioles and of alveolar ducts and walls with approxomately equal numbers of mononuclear cells (lymphocytes and macrophages) and polymorphonuclear cells. This lesion, which was specific for the antigen, was distinct from the variable granulomatous component that was directly attributable to the use of complete Freund adjubant. Development of the lesion did not correlate with the humoral immune response, as indicated by antigen-binding, precipitin, and homologous passive cutaneous anaphylaxis assays, by negative serum transfer studies, by lack of correlation with immediate and intermediate Arthuslike) skin reactivity, by absence of electron microscopic and immunofluorescent evidence for immune complex processes, and by lack of evidence for complement activation. Development of the lesion did correlate with delayed (12- to 48-hour) skin reactivity, although rigid identification of cell-mediated immunity was not possible on histologic examination."} {"id": "PMID:1267258", "title": "Airway visualization by tantalum inhalation bronchography.", "content": "A novel technique for the generation of tantalum aerosols (aerodynamic mass median diameter, 5.8 mum; sigma g, +/-2.14) for inhalation bronchography via the mouth was applied in 26 anesthetized dogs. Ventilatory patterns during periods of aerosol inhalation were controlled by either bilateral electrophrenic stimulation of the diaphragm (EPS), or by intermittent, negative pressure at the body surface (INPV). We studied patterns of tracheobronchial deposition with regard to both the sites of particle deposition longitudinally along airways within lobes, and the topographic distribution of aerosol among the lung lobes. Bronchographic patterns were accordingly studied after inhalations by either (1) EPS and INPV in the supine posture with constant tidal volumes, but varied inspiratory flow (30 to 90 liter per min); or (2) EPS with constant tidal volume and peak inspiratory flow in the prine, right, and left lateral decubitus body positions. Under all airflow conditions, the aerosol was deposited on the surfaces of ciliated airways. Deposition was nearly entirely confined to subsegmental bronchi and above with vigorous inspirations, but extended distally to subsegmental bronchi in greater proportion with decreases in the inspiratory flow. Airways among the basal lung lobes were particularly subject to distal subsegmental and bronchiolar deposition with low rates of inspiratory airflow. Regionally, the aerosol was deposited preferentially in dependent lung lobes after inhalations with EPS in the right and left lateral decubitus positions, and in the basal lung lobes with EPS in the supine posture. A greater caudocranial uniformity in lobar aerosol distribution occurred with inhalations by INPV in the supine posture, and by EPS in the prone posture. The canine model strongly suggests that for clinical inhalation bronchography, nonhomogeneities in lobar deposition may be averted by inhalations in multiple body positions, and that deposition of the aerosol may be confined to ciliated airway surfaces by inertial impaction accompanying high rates of inspiratory airflow.", "contents": "Airway visualization by tantalum inhalation bronchography. A novel technique for the generation of tantalum aerosols (aerodynamic mass median diameter, 5.8 mum; sigma g, +/-2.14) for inhalation bronchography via the mouth was applied in 26 anesthetized dogs. Ventilatory patterns during periods of aerosol inhalation were controlled by either bilateral electrophrenic stimulation of the diaphragm (EPS), or by intermittent, negative pressure at the body surface (INPV). We studied patterns of tracheobronchial deposition with regard to both the sites of particle deposition longitudinally along airways within lobes, and the topographic distribution of aerosol among the lung lobes. Bronchographic patterns were accordingly studied after inhalations by either (1) EPS and INPV in the supine posture with constant tidal volumes, but varied inspiratory flow (30 to 90 liter per min); or (2) EPS with constant tidal volume and peak inspiratory flow in the prine, right, and left lateral decubitus body positions. Under all airflow conditions, the aerosol was deposited on the surfaces of ciliated airways. Deposition was nearly entirely confined to subsegmental bronchi and above with vigorous inspirations, but extended distally to subsegmental bronchi in greater proportion with decreases in the inspiratory flow. Airways among the basal lung lobes were particularly subject to distal subsegmental and bronchiolar deposition with low rates of inspiratory airflow. Regionally, the aerosol was deposited preferentially in dependent lung lobes after inhalations with EPS in the right and left lateral decubitus positions, and in the basal lung lobes with EPS in the supine posture. A greater caudocranial uniformity in lobar aerosol distribution occurred with inhalations by INPV in the supine posture, and by EPS in the prone posture. The canine model strongly suggests that for clinical inhalation bronchography, nonhomogeneities in lobar deposition may be averted by inhalations in multiple body positions, and that deposition of the aerosol may be confined to ciliated airway surfaces by inertial impaction accompanying high rates of inspiratory airflow."} {"id": "PMID:1267259", "title": "The glycoprotein-degrading potential of peripheral leukocytes in cystic fibrosis.", "content": "In this study, the potential problems and discrepancies in cill culture techniques were avoided by isolating leukocytes from the peripheral blood of patients with cystic fibrosis and healthy human volunteers and preparing homogenates to determine the specific activities of 5 lysosomal enzymes involved in the degradation of glycoproteins. Four lysosomal hydrolases involved in the breakdown of the carbohydrate side chain were assayed using artificial substrates. The fifth enzyme, aspartylglucosamine amido hydrolase, which cleaves the linkage between this side chain and the peptide backbone, was assayed with natural substrate. No differences in enzyme activities between the 2 leukocyte sources were observed. Because no enzyme activities were deficient and no compensatory increases were noted, we concluded that the thick, glycoprotein-rich, exocrine secretions in cystic fibrosis cannot be attributed to a defect in their catabolism.", "contents": "The glycoprotein-degrading potential of peripheral leukocytes in cystic fibrosis. In this study, the potential problems and discrepancies in cill culture techniques were avoided by isolating leukocytes from the peripheral blood of patients with cystic fibrosis and healthy human volunteers and preparing homogenates to determine the specific activities of 5 lysosomal enzymes involved in the degradation of glycoproteins. Four lysosomal hydrolases involved in the breakdown of the carbohydrate side chain were assayed using artificial substrates. The fifth enzyme, aspartylglucosamine amido hydrolase, which cleaves the linkage between this side chain and the peptide backbone, was assayed with natural substrate. No differences in enzyme activities between the 2 leukocyte sources were observed. Because no enzyme activities were deficient and no compensatory increases were noted, we concluded that the thick, glycoprotein-rich, exocrine secretions in cystic fibrosis cannot be attributed to a defect in their catabolism."} {"id": "PMID:1267261", "title": "Airway responses to methacholine in allergic and nonallergic subjects.", "content": "After inhalation challenge with methacholine, bronchoconstrictor responses were produced in allergic subjects with asthma and hay fever as well as nonallergic subjects. Our results indicate that allergic persons possess a greater pulmonary responsiveness to inhalation of this parasympathomimetic agent than nonallergic subjects; however, patterns of response were different in the 2 types of allergic subjects, those with asthma and those with hay fever. Whereas both types of allergic subjects responded with changes in specific airway conductance when nonallergic subjects did not, only asthmatic subjects differed from nonallergic subjects when comparisons of spirometry were made. These data suggest that there is hypersensitivity of both central and peripheral airways in asthmatics and in the larger central airways of nonasthmatic allergic subjects.", "contents": "Airway responses to methacholine in allergic and nonallergic subjects. After inhalation challenge with methacholine, bronchoconstrictor responses were produced in allergic subjects with asthma and hay fever as well as nonallergic subjects. Our results indicate that allergic persons possess a greater pulmonary responsiveness to inhalation of this parasympathomimetic agent than nonallergic subjects; however, patterns of response were different in the 2 types of allergic subjects, those with asthma and those with hay fever. Whereas both types of allergic subjects responded with changes in specific airway conductance when nonallergic subjects did not, only asthmatic subjects differed from nonallergic subjects when comparisons of spirometry were made. These data suggest that there is hypersensitivity of both central and peripheral airways in asthmatics and in the larger central airways of nonasthmatic allergic subjects."} {"id": "PMID:1267262", "title": "The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age.", "content": "From a randomly selected population representative of the white population of Tucson, Ariz., satisfactory flow-volume data were obtained for 3,115 persons. Data from the 746 subjects who were totally free of symptoms or history of cardiorespiratory disease and who had never smoked were used in determining \"normal\" prediction equations for spirometric parameters and maximal expiratory flows. The maximal expiratory flow-volume curve showed considerable intersubject variability, but little change in shape of the mean maximal expiratory flow-volume curve was seen with advancing age when the effects of disease, insult, or injury were excluded.", "contents": "The maximal expiratory flow-volume curve. Normal standards, variability, and effects of age. From a randomly selected population representative of the white population of Tucson, Ariz., satisfactory flow-volume data were obtained for 3,115 persons. Data from the 746 subjects who were totally free of symptoms or history of cardiorespiratory disease and who had never smoked were used in determining \"normal\" prediction equations for spirometric parameters and maximal expiratory flows. The maximal expiratory flow-volume curve showed considerable intersubject variability, but little change in shape of the mean maximal expiratory flow-volume curve was seen with advancing age when the effects of disease, insult, or injury were excluded."} {"id": "PMID:1267263", "title": "Risk estimates for chronic bronchitis in smokers: a study of male-female differences.", "content": "Data from a study of chronic bronchitis and obstructive airway disease prevalence in an urban population were used to obtain estimates of the risk of these diseases in smokers and to detail the effect of cigarette smoking on the observed male: female ratio of these diseases. Standard questionnaires and measures of pulmonary function were used. Eighty-two per cent of the observed prevalence of chronic bronchitis could be attributed to cigarette smoking, and 66% of the over-all population rate was attributed to smoking. Both men and women showed a linear increase in chronic bronchitis prevalence with increased smoking. The risk of chronic bronchitis was greater for men than women in all smoking categories, but no differences in decrease in pulmonary function could be observed. Data from comparable studies were assessed and were shown to corroborate the observation that men appear to be at a greater risk for chronic bronchitis, but less clearly so for obstructive airway disease. This excess risk does not appear to be due to a difference in cigarette consumption.", "contents": "Risk estimates for chronic bronchitis in smokers: a study of male-female differences. Data from a study of chronic bronchitis and obstructive airway disease prevalence in an urban population were used to obtain estimates of the risk of these diseases in smokers and to detail the effect of cigarette smoking on the observed male: female ratio of these diseases. Standard questionnaires and measures of pulmonary function were used. Eighty-two per cent of the observed prevalence of chronic bronchitis could be attributed to cigarette smoking, and 66% of the over-all population rate was attributed to smoking. Both men and women showed a linear increase in chronic bronchitis prevalence with increased smoking. The risk of chronic bronchitis was greater for men than women in all smoking categories, but no differences in decrease in pulmonary function could be observed. Data from comparable studies were assessed and were shown to corroborate the observation that men appear to be at a greater risk for chronic bronchitis, but less clearly so for obstructive airway disease. This excess risk does not appear to be due to a difference in cigarette consumption."} {"id": "PMID:1267264", "title": "Comparison of questionnaires: the BMRC and NHLI respiratory questionnaires and a new self-completion questionnaire.", "content": "Interviewer-administered National Heart and Lung Institute (NHLI) and British Medical Research Council (BMRC) respiratory questionnaires were compared with each other and with a self-administered questionnaire of our own design in 2,350 adults enrolled in a longitudinal community study. There was a basic 10% disagreement between responses to any 2 questionnaires for all questions that inquired about a perception of a complaint or a disease, but much less disagreement for more factual questions, such as those concerning smoking. Little effect was noted from minor variations in wording, order of questions, method of administration, inclusion of other questions, or time between questionnaires (as long as this interval was less than 1 month). For questions with similar wording, the BMRC and NHLI questionnaires yielded very similar results in terms of over-all prevalence of responses, relationships to answers on an independent questionnaire, and inter-relationships of positive responses. The new self-completion questionnaire used in this study detected more abnormalities and better delineated cough and phlegm \"syndromes\" than either the NHLI or the BMRC questionnaire, and we believe that self-administration was a very satisfactory technique in the type of population surveyed in this study.", "contents": "Comparison of questionnaires: the BMRC and NHLI respiratory questionnaires and a new self-completion questionnaire. Interviewer-administered National Heart and Lung Institute (NHLI) and British Medical Research Council (BMRC) respiratory questionnaires were compared with each other and with a self-administered questionnaire of our own design in 2,350 adults enrolled in a longitudinal community study. There was a basic 10% disagreement between responses to any 2 questionnaires for all questions that inquired about a perception of a complaint or a disease, but much less disagreement for more factual questions, such as those concerning smoking. Little effect was noted from minor variations in wording, order of questions, method of administration, inclusion of other questions, or time between questionnaires (as long as this interval was less than 1 month). For questions with similar wording, the BMRC and NHLI questionnaires yielded very similar results in terms of over-all prevalence of responses, relationships to answers on an independent questionnaire, and inter-relationships of positive responses. The new self-completion questionnaire used in this study detected more abnormalities and better delineated cough and phlegm \"syndromes\" than either the NHLI or the BMRC questionnaire, and we believe that self-administration was a very satisfactory technique in the type of population surveyed in this study."} {"id": "PMID:1267265", "title": "Chronic pulmonary histoplasmosis with declining complement fixation titers and persistence of positive sputum culture. A case report.", "content": "A patient with culturally proved chronic pulmonary histoplasmosis was treated with amphotericin B. Complement fixation titers decreased but sputum cultures remained positive for Histoplasma capsulatum 5 months after original therapy. Lobectomy and a subsequent course of amphotericin B were necessary. Exceeding the minimal inhibitory concentrations of amphotericin B did not eradicate the organism and declining complement fixation titers failed to have prognostic significance.", "contents": "Chronic pulmonary histoplasmosis with declining complement fixation titers and persistence of positive sputum culture. A case report. A patient with culturally proved chronic pulmonary histoplasmosis was treated with amphotericin B. Complement fixation titers decreased but sputum cultures remained positive for Histoplasma capsulatum 5 months after original therapy. Lobectomy and a subsequent course of amphotericin B were necessary. Exceeding the minimal inhibitory concentrations of amphotericin B did not eradicate the organism and declining complement fixation titers failed to have prognostic significance."} {"id": "PMID:1267266", "title": "Cutaneous histoplasmosis.", "content": "Cutaneous lesions as a manifestation of histoplasmosis, primarily a disease of the respiratory system, are rare and most commonly appear secondary to progressive dissemination. A patient with documented progressive, disseminated histoplasmosis, having been treated previously with amphotericin B, presented on a second occasion with cutaneous lesions as the chief complaint. Biopsy and cultures of these lesions were positive for Histoplasma capsulatum. A review of the English literature revealed only 7 reported cases of secondary skin histoplasmosis in the past 20 years. All patients, including the current one, either had diseases associated with depressed immunity or were receiving steroid therapy.", "contents": "Cutaneous histoplasmosis. Cutaneous lesions as a manifestation of histoplasmosis, primarily a disease of the respiratory system, are rare and most commonly appear secondary to progressive dissemination. A patient with documented progressive, disseminated histoplasmosis, having been treated previously with amphotericin B, presented on a second occasion with cutaneous lesions as the chief complaint. Biopsy and cultures of these lesions were positive for Histoplasma capsulatum. A review of the English literature revealed only 7 reported cases of secondary skin histoplasmosis in the past 20 years. All patients, including the current one, either had diseases associated with depressed immunity or were receiving steroid therapy."} {"id": "PMID:1267267", "title": "Bacteremic Acinetobacter Herellea pneumonia with survival: case report.", "content": "A case of community-acquired pneumonia with Acinetobacter calcoacetium var. anitratus (Herellea vaginicola) is presented. Initial leukopenia and spare leukocytes in the sputum, followed by prolonged leukocytosis and fever, were unusual features of this case. The clinical significance and current antimicrobial drug therapy of acinetobacter infections are discussed.", "contents": "Bacteremic Acinetobacter Herellea pneumonia with survival: case report. A case of community-acquired pneumonia with Acinetobacter calcoacetium var. anitratus (Herellea vaginicola) is presented. Initial leukopenia and spare leukocytes in the sputum, followed by prolonged leukocytosis and fever, were unusual features of this case. The clinical significance and current antimicrobial drug therapy of acinetobacter infections are discussed."} {"id": "PMID:1267268", "title": "In vitro demonstration of specific IgE in phthalic anhydride hypersensitivity.", "content": "Clinical sensitization to phthalic anhydride occurred in a worker who developed symptoms of rhinorrhea, lacrimination, and wheezing after exposure to this chemical. Positive skin tests, provocative bronchial challenges, and a high serum titer of specific IgE (by the radioallergosorbent test) to phthalic anhydride corroborated his clinical hypersensitivity. Bronchial provocation studies using alcoholic-saline solutions of phthalic anhydride and phthalic anhydride dust resulted in immediate airway obstruction. The successful identification of specific IgE by the radioallergosorbent test demonstrates that this can be a useful in vitro technique for corroborating sensitization to this chemical.", "contents": "In vitro demonstration of specific IgE in phthalic anhydride hypersensitivity. Clinical sensitization to phthalic anhydride occurred in a worker who developed symptoms of rhinorrhea, lacrimination, and wheezing after exposure to this chemical. Positive skin tests, provocative bronchial challenges, and a high serum titer of specific IgE (by the radioallergosorbent test) to phthalic anhydride corroborated his clinical hypersensitivity. Bronchial provocation studies using alcoholic-saline solutions of phthalic anhydride and phthalic anhydride dust resulted in immediate airway obstruction. The successful identification of specific IgE by the radioallergosorbent test demonstrates that this can be a useful in vitro technique for corroborating sensitization to this chemical."} {"id": "PMID:1267273", "title": "Sepsis complications in endoscopic retrograde cholangiopancreatography.", "content": "The overall complications rate with endoscopic retrograde cholangiopancreatography (ERCP) has been justifiably small. However, serious septic sequelae have resulted in extended morbidity and occasional mortality. This occurs following successful cannulation and the injection of contrast media in two clinical conditions: (1) when ductal obstruction impairs proper drainage and (2) when a pseudocyst is injected. The initial experience at Walter Reed and Madigan Army Medical Centers with 71 attempted ERCP procedures includes two cases of pseudocyst abcess. Although this represents only a 2.8 per cent overall incidence of infection, it constitutes a 33.3 per cent rate in the six patients with pseudocysts evaluated. Therefore, it is recommended that routine ERCP be contraindicated in suspected pseudocysts.", "contents": "Sepsis complications in endoscopic retrograde cholangiopancreatography. The overall complications rate with endoscopic retrograde cholangiopancreatography (ERCP) has been justifiably small. However, serious septic sequelae have resulted in extended morbidity and occasional mortality. This occurs following successful cannulation and the injection of contrast media in two clinical conditions: (1) when ductal obstruction impairs proper drainage and (2) when a pseudocyst is injected. The initial experience at Walter Reed and Madigan Army Medical Centers with 71 attempted ERCP procedures includes two cases of pseudocyst abcess. Although this represents only a 2.8 per cent overall incidence of infection, it constitutes a 33.3 per cent rate in the six patients with pseudocysts evaluated. Therefore, it is recommended that routine ERCP be contraindicated in suspected pseudocysts."} {"id": "PMID:1267274", "title": "Ingested foreign bodies of the gastrointestinal tract.", "content": "Seven case reports of ingested foreign bodies are presented. Although ingestion of foreign bodies may be a frequent occurrence, 80 per cent of documented ingested foreign bodies pass through the gastrointestinal tract spontaneously. The most frequent victims of foreign body ingestion are children, denture-wearing adults, and the mentally ill. Most foreign bodies are best managed by \"intelligent neglect\". Some require surgical removal because of perforation hemorrhage or obstruction. The ileocecal region is the most common site for perforation. Close observation for signs of perforation, hemorrhage, and/or obstruction is mandatory.", "contents": "Ingested foreign bodies of the gastrointestinal tract. Seven case reports of ingested foreign bodies are presented. Although ingestion of foreign bodies may be a frequent occurrence, 80 per cent of documented ingested foreign bodies pass through the gastrointestinal tract spontaneously. The most frequent victims of foreign body ingestion are children, denture-wearing adults, and the mentally ill. Most foreign bodies are best managed by \"intelligent neglect\". Some require surgical removal because of perforation hemorrhage or obstruction. The ileocecal region is the most common site for perforation. Close observation for signs of perforation, hemorrhage, and/or obstruction is mandatory."} {"id": "PMID:1267275", "title": "Efficiency of tube paracentesis without lavage in detecting minimal intraperitoneal bleeding.", "content": "Tube paracentesis without lavage yielded a positive result in an injured child whose condition was clinically stable and who would otherwise have undoubtedly been observed briefly in the hospital and then discharged. On the basis of the positive paracentesis alone, laparotomy was performed which revealed a very minimal injury of the splenic capsule and intraperitoneal bleeding measured at less than 25 cc. The case is presented because it offers evidence in favor of the efficiency of this technique in detecting intraperitoneal bleeding. This case combined with previous experience leads us to believe this is a very useful tool in the evaluation of patients with blunt abdominal trauma.", "contents": "Efficiency of tube paracentesis without lavage in detecting minimal intraperitoneal bleeding. Tube paracentesis without lavage yielded a positive result in an injured child whose condition was clinically stable and who would otherwise have undoubtedly been observed briefly in the hospital and then discharged. On the basis of the positive paracentesis alone, laparotomy was performed which revealed a very minimal injury of the splenic capsule and intraperitoneal bleeding measured at less than 25 cc. The case is presented because it offers evidence in favor of the efficiency of this technique in detecting intraperitoneal bleeding. This case combined with previous experience leads us to believe this is a very useful tool in the evaluation of patients with blunt abdominal trauma."} {"id": "PMID:1267277", "title": "The role of pericardiotomy in treatment of pericarditis with effusion.", "content": "Experience with 23 patients with pericarditis and pericardial effusion is discussed. The methods of drainage with their relative merits are mentioned, as are the etiology of pericarditis, signs and symptoms of the disease as well as various techniques for establishing the diagnosis.", "contents": "The role of pericardiotomy in treatment of pericarditis with effusion. Experience with 23 patients with pericarditis and pericardial effusion is discussed. The methods of drainage with their relative merits are mentioned, as are the etiology of pericarditis, signs and symptoms of the disease as well as various techniques for establishing the diagnosis."} {"id": "PMID:1267279", "title": "Obturator hernia: report of a case and brief review of its status.", "content": "The only case of obturator hernia in over 230,000 admissions is discussed. In the review of the recent English literature, a total of 30 cases, including our own, was collected. Characteristics of the condition were analyzed. The median age of the patients was 67 years; the majority were females in a ratio of 9:1 and both sides were equally affected. This entity occurs with the signs and symptoms of small bowel obstruction and, in almost one half of the patients, the pathognomonic Howship-Romberg sign.", "contents": "Obturator hernia: report of a case and brief review of its status. The only case of obturator hernia in over 230,000 admissions is discussed. In the review of the recent English literature, a total of 30 cases, including our own, was collected. Characteristics of the condition were analyzed. The median age of the patients was 67 years; the majority were females in a ratio of 9:1 and both sides were equally affected. This entity occurs with the signs and symptoms of small bowel obstruction and, in almost one half of the patients, the pathognomonic Howship-Romberg sign."} {"id": "PMID:1267280", "title": "Transomental hernia.", "content": "Transomental hernia is a very rare condition with less than 50 cases reported. This hernia nearly always causes bowel obstruction and may result in a high mortality rate because of strangulation and gangrene. A typical case of transomental hernia is presented and the literature is reviewed with emphasis on the need for early diagnosis and operation.", "contents": "Transomental hernia. Transomental hernia is a very rare condition with less than 50 cases reported. This hernia nearly always causes bowel obstruction and may result in a high mortality rate because of strangulation and gangrene. A typical case of transomental hernia is presented and the literature is reviewed with emphasis on the need for early diagnosis and operation."} {"id": "PMID:1267281", "title": "Paracecal hernia: case report and review of the literature.", "content": "A case of paracecal hernia successfully treated operatively is described. Review of the literature revealed 145 previously reported cases. Our case is added. Pertinent anatomy predisposing to paracecal hernia is reviewed. Roentgenographic signs of paracecal hernia are presented. Clinical signs and symptoms are discussed.", "contents": "Paracecal hernia: case report and review of the literature. A case of paracecal hernia successfully treated operatively is described. Review of the literature revealed 145 previously reported cases. Our case is added. Pertinent anatomy predisposing to paracecal hernia is reviewed. Roentgenographic signs of paracecal hernia are presented. Clinical signs and symptoms are discussed."} {"id": "PMID:1267282", "title": "Primary adenocarcinoma of lung in a child: review of the literature.", "content": "A rare case of primary bronchogenic carcinoma in a 6-year-old child is presented. Review of the literature reveals an additional 38 cases from which observations are made. Although an usual lesion in childhood, bronchogenic carcinoma does occur and should be considered early for appropriate therapy and for prognosis to be favorably affected.", "contents": "Primary adenocarcinoma of lung in a child: review of the literature. A rare case of primary bronchogenic carcinoma in a 6-year-old child is presented. Review of the literature reveals an additional 38 cases from which observations are made. Although an usual lesion in childhood, bronchogenic carcinoma does occur and should be considered early for appropriate therapy and for prognosis to be favorably affected."} {"id": "PMID:1267283", "title": "Ruptured abdominal aortic aneurysms: review of 33 cases treated surgically and discussion of prognostic indicators.", "content": "Over an eight-year peroid at NCBH, 33 patients were operated for ruptured abdominal aortic aneurysm. Factors associated with an increased mortality included preoperative blood urea nitrogen levels of more than 20 mg per cent, severe preoperative hypotension, duration of symptoms of less than 24 hours, free peritoneal rupture and blood transfusions of greater than 19 units. Preoperative hypotension was the most selective preoperative prognostic parameter. From a review of this and other reported series, it was concluded that reduced mortality from ruptured abdominal aortic aneurysm can best be achieved by prompt diagnosis followed by surgical treatment before cardiovascular collapse can occur.", "contents": "Ruptured abdominal aortic aneurysms: review of 33 cases treated surgically and discussion of prognostic indicators. Over an eight-year peroid at NCBH, 33 patients were operated for ruptured abdominal aortic aneurysm. Factors associated with an increased mortality included preoperative blood urea nitrogen levels of more than 20 mg per cent, severe preoperative hypotension, duration of symptoms of less than 24 hours, free peritoneal rupture and blood transfusions of greater than 19 units. Preoperative hypotension was the most selective preoperative prognostic parameter. From a review of this and other reported series, it was concluded that reduced mortality from ruptured abdominal aortic aneurysm can best be achieved by prompt diagnosis followed by surgical treatment before cardiovascular collapse can occur."} {"id": "PMID:1267286", "title": "Oblique muscle splitting incision for cervical laminotomy.", "content": "A muscle-splitting incision for cervical disc disease is described. It is based upon sound surgical principles. There have been no wound complications in the last 60 patients treated by the authors. Its most stringent demand is that the surgeon be familiar with the anatomical planes to be certain of the level which he wishes to explore.", "contents": "Oblique muscle splitting incision for cervical laminotomy. A muscle-splitting incision for cervical disc disease is described. It is based upon sound surgical principles. There have been no wound complications in the last 60 patients treated by the authors. Its most stringent demand is that the surgeon be familiar with the anatomical planes to be certain of the level which he wishes to explore."} {"id": "PMID:1267287", "title": "Staging laparotomy for Hodgkin's disease.", "content": "We reviewed 39 patients with untreated Hodgkin's disease who underwent staging laparotomy and such cases in the English literature over the past two-and-a-half years. In the group of institutions in our compilation, the accuracies of clinically positive and negative judgments of liver involvement were 28 per cent and 95.4 per cent respectively, while in our institution the accuracies were 100 per cent and 95 percent respectively. The accuracies of the clinically positive and negative determinations of splenic involvement were 61.2 per cent and 67.3 per cent respectively after histological examination, whereas we had accuracies of 100 per cent and 74 per cent respectively. The accuracies of the clinically positive and negative determination of lymph nodes were 72.1 per cent and 86.7 per cent respectively, whereas the results were 70.6 per cent and 100 per cent respectively in our 39 cases. The percentage of complications was 10 per cent and the mortality rate was 0.9 per cent among 719 staging laparotomies. The common complications were atelectasis, pneumonia, wound infection and dehiscence, abscess, intestinal obstruction and thrombocytosis. We think more aggressive staging laparotomy should be performed for Hodgkin's disease under one surgeon or one surgical team.", "contents": "Staging laparotomy for Hodgkin's disease. We reviewed 39 patients with untreated Hodgkin's disease who underwent staging laparotomy and such cases in the English literature over the past two-and-a-half years. In the group of institutions in our compilation, the accuracies of clinically positive and negative judgments of liver involvement were 28 per cent and 95.4 per cent respectively, while in our institution the accuracies were 100 per cent and 95 percent respectively. The accuracies of the clinically positive and negative determinations of splenic involvement were 61.2 per cent and 67.3 per cent respectively after histological examination, whereas we had accuracies of 100 per cent and 74 per cent respectively. The accuracies of the clinically positive and negative determination of lymph nodes were 72.1 per cent and 86.7 per cent respectively, whereas the results were 70.6 per cent and 100 per cent respectively in our 39 cases. The percentage of complications was 10 per cent and the mortality rate was 0.9 per cent among 719 staging laparotomies. The common complications were atelectasis, pneumonia, wound infection and dehiscence, abscess, intestinal obstruction and thrombocytosis. We think more aggressive staging laparotomy should be performed for Hodgkin's disease under one surgeon or one surgical team."} {"id": "PMID:1267288", "title": "Wound dehiscence after cholecystectomy and salmonella infection.", "content": "A case of a wound dehiscence following a Salmonella wound infection is reported. Cholecystectomy for the typhoid carrier state is not an uncommon operation and carries the risk of Salmonella wound infection in about 7 per cent of the cases. Wound dehiscence with this type of infection has not previously been reported.", "contents": "Wound dehiscence after cholecystectomy and salmonella infection. A case of a wound dehiscence following a Salmonella wound infection is reported. Cholecystectomy for the typhoid carrier state is not an uncommon operation and carries the risk of Salmonella wound infection in about 7 per cent of the cases. Wound dehiscence with this type of infection has not previously been reported."} {"id": "PMID:1267289", "title": "Emphysematous cholecystitis: report of a case.", "content": "A case is reported of emphysematous cholecystitis that occurred seven months after vagotomy and hemigastrectomy (with Billroth II reconstruction). It was successfully treated by means of initial cholecystostomy and interim cholecystectomy six weeks later. Although it has been urged by some that an emergency operation is always indicated in this condition, in the case presented, the timing of the operation was determined by the overall clinical picture of the patient.", "contents": "Emphysematous cholecystitis: report of a case. A case is reported of emphysematous cholecystitis that occurred seven months after vagotomy and hemigastrectomy (with Billroth II reconstruction). It was successfully treated by means of initial cholecystostomy and interim cholecystectomy six weeks later. Although it has been urged by some that an emergency operation is always indicated in this condition, in the case presented, the timing of the operation was determined by the overall clinical picture of the patient."} {"id": "PMID:1267290", "title": "Patient acceptance of local anesthesia for breast biopsy.", "content": "Three out of every four patients undergoing breast biopsy found the outpatient local-anesthesia method acceptable in this study. Patient acceptance was greater among those who experienced less pain and anxiety. This suggests that acceptance could be increased by more complete preoperative explanation to the patient, adequate premedication, properly administered local anesthesia and gentle technique. Acceptance would also probably be far greater in a private practice setting than in the instititutional and sometimes impersonal setting of a large federal hospital. Breast biopsy under local anesthesia has not compromised survival rates or increased local recurrence. When it is done on an outpatient basis, hospital costs have been reduced at least threefold. It is apparent, then, that patient objection is not a deterrent to the use of breast biopsy under local anesthesia on an outpatient basis. For patients with dominant breast masses, this modality can be added to any plan of management which seeks to reduce patient risk and inconvencience, diminish hospital costs and alleviate bed demand all without impairing diagnostic accuracy or long-term survival.", "contents": "Patient acceptance of local anesthesia for breast biopsy. Three out of every four patients undergoing breast biopsy found the outpatient local-anesthesia method acceptable in this study. Patient acceptance was greater among those who experienced less pain and anxiety. This suggests that acceptance could be increased by more complete preoperative explanation to the patient, adequate premedication, properly administered local anesthesia and gentle technique. Acceptance would also probably be far greater in a private practice setting than in the instititutional and sometimes impersonal setting of a large federal hospital. Breast biopsy under local anesthesia has not compromised survival rates or increased local recurrence. When it is done on an outpatient basis, hospital costs have been reduced at least threefold. It is apparent, then, that patient objection is not a deterrent to the use of breast biopsy under local anesthesia on an outpatient basis. For patients with dominant breast masses, this modality can be added to any plan of management which seeks to reduce patient risk and inconvencience, diminish hospital costs and alleviate bed demand all without impairing diagnostic accuracy or long-term survival."} {"id": "PMID:1267291", "title": "Recurrent pancreatitis and jaundice: report of a case in an eleven-year-old girl.", "content": "An 11-year-old girl had recurrent pancreatitis and jaundice caused by fusiform dilatation of the common bile duct, a variant of choledochal cyst. The treatment was Roux-en-Y choledochojejunostomy and cholecystectomy. There has been no recurrence of symptoms during subsequent follow-up.", "contents": "Recurrent pancreatitis and jaundice: report of a case in an eleven-year-old girl. An 11-year-old girl had recurrent pancreatitis and jaundice caused by fusiform dilatation of the common bile duct, a variant of choledochal cyst. The treatment was Roux-en-Y choledochojejunostomy and cholecystectomy. There has been no recurrence of symptoms during subsequent follow-up."} {"id": "PMID:1267292", "title": "Teratoid tumors of the mediastinum.", "content": "Anterior mediastinum is the third commonest location for teratoid tumors besides the ovaries and the testes. Although there is still some confusion about the classification of these tumors, most authors now agree that the term dermoid cyst should be used for cystic lesions containing ectodermal and mesodermal elements. Teratoma should be reserved for solid or cystic lesions containing derivatives of all the three germ layers. The clinical manifestations offer no clue to their malignant potentiality. Chest roentgenogram, tomogram and esophagogram are useful, and aortic arch studies may be indicated in some cases to exclude aortic aneurysms. Surgical excision offers the best method of diagnosis and treatment. The prognosis is excellent for benign teratoids but poor for malignant teratoids, especially in children and young adults.", "contents": "Teratoid tumors of the mediastinum. Anterior mediastinum is the third commonest location for teratoid tumors besides the ovaries and the testes. Although there is still some confusion about the classification of these tumors, most authors now agree that the term dermoid cyst should be used for cystic lesions containing ectodermal and mesodermal elements. Teratoma should be reserved for solid or cystic lesions containing derivatives of all the three germ layers. The clinical manifestations offer no clue to their malignant potentiality. Chest roentgenogram, tomogram and esophagogram are useful, and aortic arch studies may be indicated in some cases to exclude aortic aneurysms. Surgical excision offers the best method of diagnosis and treatment. The prognosis is excellent for benign teratoids but poor for malignant teratoids, especially in children and young adults."} {"id": "PMID:1267294", "title": "Carotidoesophageal fistula complicating carcinoma of the esophagus: report of a case.", "content": "A case of carotidoesophageal fistula complicating carcinoma of the esophagus is reported for the first time in Iran. Review of the literature up to 1972 revealed four previous reports of this complication and only 92 reported cases of aortoesophageal fistula due to carcinoma of the esophagus.", "contents": "Carotidoesophageal fistula complicating carcinoma of the esophagus: report of a case. A case of carotidoesophageal fistula complicating carcinoma of the esophagus is reported for the first time in Iran. Review of the literature up to 1972 revealed four previous reports of this complication and only 92 reported cases of aortoesophageal fistula due to carcinoma of the esophagus."} {"id": "PMID:1267296", "title": "[Cloverleaf syndrome. Presentation of four cases (author's transl)].", "content": "Four cases of cloverleaf syndrome are presented. Authors agree with recent opinions that this alteration is a significant indication that may be presented by diseases which develop craniosynostosis very early (acrocephalosyndactyly, thanatophoric, dwarfism, Crouzon's disease, etc.). Etiopathogenic considerations are made about morphology and prognosis in this disease of unknown etiology.", "contents": "[Cloverleaf syndrome. Presentation of four cases (author's transl)]. Four cases of cloverleaf syndrome are presented. Authors agree with recent opinions that this alteration is a significant indication that may be presented by diseases which develop craniosynostosis very early (acrocephalosyndactyly, thanatophoric, dwarfism, Crouzon's disease, etc.). Etiopathogenic considerations are made about morphology and prognosis in this disease of unknown etiology."} {"id": "PMID:1267297", "title": "[Digestive associated malformations in esophageal atresia. A study of 125 patients (author's transl)].", "content": "The incidence of digestive malformations associated to esophageal atresia and tracheoesophageal fistula is reviewed in a series of 125 surgically treated patients during the last five years' period. A correlation is drawn with other associated malformations. Its influence upon the mortality rate is stressed.", "contents": "[Digestive associated malformations in esophageal atresia. A study of 125 patients (author's transl)]. The incidence of digestive malformations associated to esophageal atresia and tracheoesophageal fistula is reviewed in a series of 125 surgically treated patients during the last five years' period. A correlation is drawn with other associated malformations. Its influence upon the mortality rate is stressed."} {"id": "PMID:1267298", "title": "[Caudal regression syndrome (report of 4 cases) (author's transl)].", "content": "Four cases of caudal regression syndrome with partial or complete sacrococcigeal agenesis are presented. One of them also had agenesis of the last lumbar vertebrae. Urinary, gluteae and inferior limb malformations were found in all four. Special emphasis is placed on the importance of the early knowledge of these malformations in order to avoid secondary effects to neurogenic bladder (urinary infections, vesico-ureteral reflux, hipofunctional kidney) caused by a delayed diagnosis. Maternal diabetes in one case and skeletal alterations (hexadactily, lack of one hand) in another were found among the family history. A very uncommon association with Goldenhar's syndrome and Klippel-Feil's syndrome in one case, and with \"situs inversus totalis\" in another are described. The possible ethiologies of the syndrome are being discussed.", "contents": "[Caudal regression syndrome (report of 4 cases) (author's transl)]. Four cases of caudal regression syndrome with partial or complete sacrococcigeal agenesis are presented. One of them also had agenesis of the last lumbar vertebrae. Urinary, gluteae and inferior limb malformations were found in all four. Special emphasis is placed on the importance of the early knowledge of these malformations in order to avoid secondary effects to neurogenic bladder (urinary infections, vesico-ureteral reflux, hipofunctional kidney) caused by a delayed diagnosis. Maternal diabetes in one case and skeletal alterations (hexadactily, lack of one hand) in another were found among the family history. A very uncommon association with Goldenhar's syndrome and Klippel-Feil's syndrome in one case, and with \"situs inversus totalis\" in another are described. The possible ethiologies of the syndrome are being discussed."} {"id": "PMID:1267299", "title": "[Single ventricle and related anomalies. Anatomic findings in 30 cases. Diagnostic and therapeutic implications (author's transl)].", "content": "Anatomic characteristics are studied in 30 cases of single ventricle and related anomalies. Cases are distributed into 6 groups according to: a) the derangement in the expansi\u00f3n of the atrioventricular canal towards the \"bulbus cordis\", which may be either defective (groups I, II and III) or excessive (groups IV and V), and b) the hypoplastic nature of the ventricular septum (group VI). The most important conclusions are: 1) An L-bulboventricular loop was found in 43.47% of the entire material; all of them pertained to groups I, II and III. 2) A normal position of the great arteries was uncommon, being encountered in 13.4% of the cases. An aorta situated anteriorly and to the left was present in 30.43% of the cases included in groups IV and V. 3) Obstructive anomalies of either outflow tract were discovered in 66.6% of the entire material, regardless of the type of bulboventricular loop. 4) The left atrioventricular orifice was found to be abnormally small in 56.66% of the total case material and in 88.23% of the cases pertaining to groups I, II and III. 5) A mitral atresia was encountered in two cases pertaining to groups I and II. The criteria which have been used to admit cases with this association of anomalies have been established in previous publications by one of the authors of the present study. 6) The changes in the spacial orientation of the leaflets of the right atrioventricular orifice in cases with an L-bulboventricular loop are attributed to the rotation of the heart around its longitudinal axis which takes place in cases with levocardia and mesocardia. 7) A preoperative study as accurate as possible is necessary in order to establish a rational approach to the surgical management of these patients.", "contents": "[Single ventricle and related anomalies. Anatomic findings in 30 cases. Diagnostic and therapeutic implications (author's transl)]. Anatomic characteristics are studied in 30 cases of single ventricle and related anomalies. Cases are distributed into 6 groups according to: a) the derangement in the expansi\u00f3n of the atrioventricular canal towards the \"bulbus cordis\", which may be either defective (groups I, II and III) or excessive (groups IV and V), and b) the hypoplastic nature of the ventricular septum (group VI). The most important conclusions are: 1) An L-bulboventricular loop was found in 43.47% of the entire material; all of them pertained to groups I, II and III. 2) A normal position of the great arteries was uncommon, being encountered in 13.4% of the cases. An aorta situated anteriorly and to the left was present in 30.43% of the cases included in groups IV and V. 3) Obstructive anomalies of either outflow tract were discovered in 66.6% of the entire material, regardless of the type of bulboventricular loop. 4) The left atrioventricular orifice was found to be abnormally small in 56.66% of the total case material and in 88.23% of the cases pertaining to groups I, II and III. 5) A mitral atresia was encountered in two cases pertaining to groups I and II. The criteria which have been used to admit cases with this association of anomalies have been established in previous publications by one of the authors of the present study. 6) The changes in the spacial orientation of the leaflets of the right atrioventricular orifice in cases with an L-bulboventricular loop are attributed to the rotation of the heart around its longitudinal axis which takes place in cases with levocardia and mesocardia. 7) A preoperative study as accurate as possible is necessary in order to establish a rational approach to the surgical management of these patients."} {"id": "PMID:1267300", "title": "[CSF. changes in partially treated bacterial meningitis (author's transl)].", "content": "Review of 102 admissions of children (one month to seven years of age) with bacterial meningitis is presented. 46 of the patients (45%) had been treated previously with one or more antibiotics. Previous treatment made culture of CSF negative in a statistically significant (p less than 0.001) number of cases, mainly in meningococcal meningitis. There were no significant differences in the levels of CSF glucose, proteins and WBC's between both groups. A decrease of the percentage PMN/lymphocytes was found in the CSF of the partially treated group. In 7 out of 102 no more than two CSF pathological findings were present. In 5 or 7 CSF cultures were positive. In the other two there were pathological changes in CSF even with correct dosage of previous antibiotics. In 4 patients with positive cultures and little changes in CSF on admission, LP after 48 hours of correct treatment showed an increase in the alterations of CSF. This could mean that previous low dosage antibiotic treatment should not modify CSF findings enough not to make correct diagnosis.", "contents": "[CSF. changes in partially treated bacterial meningitis (author's transl)]. Review of 102 admissions of children (one month to seven years of age) with bacterial meningitis is presented. 46 of the patients (45%) had been treated previously with one or more antibiotics. Previous treatment made culture of CSF negative in a statistically significant (p less than 0.001) number of cases, mainly in meningococcal meningitis. There were no significant differences in the levels of CSF glucose, proteins and WBC's between both groups. A decrease of the percentage PMN/lymphocytes was found in the CSF of the partially treated group. In 7 out of 102 no more than two CSF pathological findings were present. In 5 or 7 CSF cultures were positive. In the other two there were pathological changes in CSF even with correct dosage of previous antibiotics. In 4 patients with positive cultures and little changes in CSF on admission, LP after 48 hours of correct treatment showed an increase in the alterations of CSF. This could mean that previous low dosage antibiotic treatment should not modify CSF findings enough not to make correct diagnosis."} {"id": "PMID:1267308", "title": "Simplified perimetry.", "content": "A simplified method of performing peripheral visual field examination with the Krimsky Eyecup is described. This technique is compared with Goldman perimetry in a series of patients with a variety of ocular pathology. The peripheral visual fields obtained by these two methods compare closely.", "contents": "Simplified perimetry. A simplified method of performing peripheral visual field examination with the Krimsky Eyecup is described. This technique is compared with Goldman perimetry in a series of patients with a variety of ocular pathology. The peripheral visual fields obtained by these two methods compare closely."} {"id": "PMID:1267302", "title": "[Semiologic value of tonic-axial crises in children (author's transl)].", "content": "The tonic-axial crises described clinically and by electroencephalo-grams by Ouachi, Roger and Gastaut in 1961, are encountered with relative frequency in specific forms of infantile epilepsy and they establish the principal nucleus of the appearing manifestations in some cases of childhood epileptic encephalopathy. We have studied 43 epileptic children who have displayed tonic-axial crises, taking into consideration the absence or existence of concrete antecedents of cerebral attack, the moment of appearance of the tonix-axial crises in relation to the commencement of the critical manifestations, the type or types of epileptic crises, the circumstances of appearance of tonic-axial crises and its influence upon the further development of the child. Its physiopathology is questioned and the tonic-axial crises is considered as a semiologic crossroad in the evolution in the secondary generalized epilepsy.", "contents": "[Semiologic value of tonic-axial crises in children (author's transl)]. The tonic-axial crises described clinically and by electroencephalo-grams by Ouachi, Roger and Gastaut in 1961, are encountered with relative frequency in specific forms of infantile epilepsy and they establish the principal nucleus of the appearing manifestations in some cases of childhood epileptic encephalopathy. We have studied 43 epileptic children who have displayed tonic-axial crises, taking into consideration the absence or existence of concrete antecedents of cerebral attack, the moment of appearance of the tonix-axial crises in relation to the commencement of the critical manifestations, the type or types of epileptic crises, the circumstances of appearance of tonic-axial crises and its influence upon the further development of the child. Its physiopathology is questioned and the tonic-axial crises is considered as a semiologic crossroad in the evolution in the secondary generalized epilepsy."} {"id": "PMID:1267303", "title": "[Oral-facial-digital syndrome in male (author's transl)].", "content": "One case of oral-facial-digital syndrome (Papillon-L\u00e9age and Psaume) is presented. This is the second one reported on a patient with normal male karyotipe. Clinical data and genetic aspects are commented in relation with this new case in a 46 XY male.", "contents": "[Oral-facial-digital syndrome in male (author's transl)]. One case of oral-facial-digital syndrome (Papillon-L\u00e9age and Psaume) is presented. This is the second one reported on a patient with normal male karyotipe. Clinical data and genetic aspects are commented in relation with this new case in a 46 XY male."} {"id": "PMID:1267309", "title": "Solar retinopathy.", "content": "Two cases of solar retinopathy following prolonged sun gazing are presented. Both patients were seen within an interval of 11 months, both with the diagnosis of schizophrenia paranoid type. These patients gave a history of sun gazing while praying to God, resulting in pigmentary disturbances of the macula, characterized by central and parafoveal depigmentation with perifoveal hyperpigmentation, as well as permanent impairment of vision in both eyes.", "contents": "Solar retinopathy. Two cases of solar retinopathy following prolonged sun gazing are presented. Both patients were seen within an interval of 11 months, both with the diagnosis of schizophrenia paranoid type. These patients gave a history of sun gazing while praying to God, resulting in pigmentary disturbances of the macula, characterized by central and parafoveal depigmentation with perifoveal hyperpigmentation, as well as permanent impairment of vision in both eyes."} {"id": "PMID:1267304", "title": "[Brain scanning in children (author's transl)].", "content": "This report is concerned with evaluation of brain scintigraphy in the detection of brain tumors in children. Brain scans have been reviewed in 309 cases and were evaluated in 182 patients; brain tumor suspicious was present in 41 childrens. True positive results were obtained in 73% of brains tumors and true negative results in 5% with other diseases. There were either false positive or false negative results in 21% of scans. Results are compared to other series reported, showing similar findings. Finally the importance of this type of investigation is stressed.", "contents": "[Brain scanning in children (author's transl)]. This report is concerned with evaluation of brain scintigraphy in the detection of brain tumors in children. Brain scans have been reviewed in 309 cases and were evaluated in 182 patients; brain tumor suspicious was present in 41 childrens. True positive results were obtained in 73% of brains tumors and true negative results in 5% with other diseases. There were either false positive or false negative results in 21% of scans. Results are compared to other series reported, showing similar findings. Finally the importance of this type of investigation is stressed."} {"id": "PMID:1267305", "title": "[Congenital malformations associated with esophageal atresia (author's transl)].", "content": "In 67 patients with esophageal atresia we have found associated congenital anomalies in over 80% and 10 children could be considered as carriers of Vater association. The various malformations are reported and their etiopathogenic factors considered.", "contents": "[Congenital malformations associated with esophageal atresia (author's transl)]. In 67 patients with esophageal atresia we have found associated congenital anomalies in over 80% and 10 children could be considered as carriers of Vater association. The various malformations are reported and their etiopathogenic factors considered."} {"id": "PMID:1267310", "title": "The use of polyglycolic acid sutures in outpatient cataract surgery.", "content": "The use of 7-0 polyglycolic acid (Dexon) sutures in 200 consecutive outpatient cataract extractions is described and compared with the use of 7-0 chromic gut sutures in 200 consecutive outpatient cataract extractions. The polyglycolic acid sutures appeared to be more comfortable to the patient than the chromic gut sutures, they absorbed at a constant, steady rate compared to a variable rate for the gut sutures and there were less postoperative complications with the polyglycolic acid sutures than with the gut sutures.", "contents": "The use of polyglycolic acid sutures in outpatient cataract surgery. The use of 7-0 polyglycolic acid (Dexon) sutures in 200 consecutive outpatient cataract extractions is described and compared with the use of 7-0 chromic gut sutures in 200 consecutive outpatient cataract extractions. The polyglycolic acid sutures appeared to be more comfortable to the patient than the chromic gut sutures, they absorbed at a constant, steady rate compared to a variable rate for the gut sutures and there were less postoperative complications with the polyglycolic acid sutures than with the gut sutures."} {"id": "PMID:1267306", "title": "[Guillain-Barre's syndrome in childhood (author's transl)].", "content": "Seventeen cases of Guillain-Barr\u00e9's syndrome aged between 14 month ans 7 years are studied from clinical, analytical and evolutives aspects. Neither sex nor season predominance occurs. Sixteen of the patients had a previous viral or bacterial infection. Difficulty in walking was the main symptom at the onset of illness. Arreflexia and motot paralysis were always symmetrical and ascending. Albumino-cytological dissociation in the C.S.F. was found in the whole group. An evolutive study was made of the recovery of movement, C.S.F. and tendon reflexes which occurred in this order except in two cases which showed abnormal evolution. We emphasize the extent and frequency of respiratory difficulties at the onset of illness. Some etiopathogenic aspects, the lack of specifity of the syndrome and the differences of the diagnosis with that of poliomyelitis are commented. We point out the lack of effect of the corticosteroids treatment and the positive effects of phisiotherapy after the acute stage.", "contents": "[Guillain-Barre's syndrome in childhood (author's transl)]. Seventeen cases of Guillain-Barr\u00e9's syndrome aged between 14 month ans 7 years are studied from clinical, analytical and evolutives aspects. Neither sex nor season predominance occurs. Sixteen of the patients had a previous viral or bacterial infection. Difficulty in walking was the main symptom at the onset of illness. Arreflexia and motot paralysis were always symmetrical and ascending. Albumino-cytological dissociation in the C.S.F. was found in the whole group. An evolutive study was made of the recovery of movement, C.S.F. and tendon reflexes which occurred in this order except in two cases which showed abnormal evolution. We emphasize the extent and frequency of respiratory difficulties at the onset of illness. Some etiopathogenic aspects, the lack of specifity of the syndrome and the differences of the diagnosis with that of poliomyelitis are commented. We point out the lack of effect of the corticosteroids treatment and the positive effects of phisiotherapy after the acute stage."} {"id": "PMID:1267311", "title": "Superior oblique tendon sheath syndrome: an unusual case.", "content": "It is now recognized that the clinical findings of Brown's superior oblique tendon sheath syndrome can be caused by a variety of abnormalities. This has led to classification into \"true\" and \"simulated\" sheath syndromes. This report describes a case of simulated sheath syndrome caused by an anomalous fibrous band between the superior oblique tendon sheath and the upper nasal intermuscular quadrant. This unusual anomaly results in functional shortening of the sheath. Division of the band eliminated the restrictions on traction test and improved elevation in all fields postoperatively.", "contents": "Superior oblique tendon sheath syndrome: an unusual case. It is now recognized that the clinical findings of Brown's superior oblique tendon sheath syndrome can be caused by a variety of abnormalities. This has led to classification into \"true\" and \"simulated\" sheath syndromes. This report describes a case of simulated sheath syndrome caused by an anomalous fibrous band between the superior oblique tendon sheath and the upper nasal intermuscular quadrant. This unusual anomaly results in functional shortening of the sheath. Division of the band eliminated the restrictions on traction test and improved elevation in all fields postoperatively."} {"id": "PMID:1267312", "title": "The intraocular pressure: clinical aspects.", "content": "Only a few conclusions can be mentioned: The IO pressure of the normal eye is not fixed, but shows spontaneous variations of pulsatory, respiratory, vasomotoric and diurnal type. The highest and lowest point of a 1 minute tracing can differ for 8 mm Hg. Very short acting tonometers are, therefore, less reliable than those with slower reactions, which will average some of the quicker oscillations. Normal limits of diurnal variations are 5 mm Hg with peaks below 25 mm Hg and differences between right and left eye of less than 4 mm Hg. The range of pressure of an eye is more important than a definite value which is true for the moment only. Factors which influence the IO pressure in healthy subjects are discussed in detail, such as age, sex, eye muscles, sports, muscular spasmus, child birth, position of the body, real or simulated tonometry, and mental stress. Difficulties in tonometry are discussed. In applananation tonometry, +/- 2.5 mm Hg must be accepted as the possible error of clinical results. This is not caused by any lack in the construction of the instrument, but by the combination of interobserver variation in reading the instrument, spontaneous pressure changea and an individually different decrease of pressure in consequence of repeated measurements. It is concluded that the rigidity of the living eye cannot be measured with a satisfactory degree of exactness. For the clinical purpose of early diagnosis, the diurnal tension curve combined with the tonography test of the author are the best methods. Early normalization of intraocular pressure is the safest means to prevent damage of the optic nerve. In spite of the individual variations of pressure and the inaccuracies of any single tonometry, the present methods of tonometry are clinically sufficient to form an opinion about the diagnosis and also about the success of our treatment, the aim of which is to normalize the pressure through the 24 hours below 20 mm Hg.", "contents": "The intraocular pressure: clinical aspects. Only a few conclusions can be mentioned: The IO pressure of the normal eye is not fixed, but shows spontaneous variations of pulsatory, respiratory, vasomotoric and diurnal type. The highest and lowest point of a 1 minute tracing can differ for 8 mm Hg. Very short acting tonometers are, therefore, less reliable than those with slower reactions, which will average some of the quicker oscillations. Normal limits of diurnal variations are 5 mm Hg with peaks below 25 mm Hg and differences between right and left eye of less than 4 mm Hg. The range of pressure of an eye is more important than a definite value which is true for the moment only. Factors which influence the IO pressure in healthy subjects are discussed in detail, such as age, sex, eye muscles, sports, muscular spasmus, child birth, position of the body, real or simulated tonometry, and mental stress. Difficulties in tonometry are discussed. In applananation tonometry, +/- 2.5 mm Hg must be accepted as the possible error of clinical results. This is not caused by any lack in the construction of the instrument, but by the combination of interobserver variation in reading the instrument, spontaneous pressure changea and an individually different decrease of pressure in consequence of repeated measurements. It is concluded that the rigidity of the living eye cannot be measured with a satisfactory degree of exactness. For the clinical purpose of early diagnosis, the diurnal tension curve combined with the tonography test of the author are the best methods. Early normalization of intraocular pressure is the safest means to prevent damage of the optic nerve. In spite of the individual variations of pressure and the inaccuracies of any single tonometry, the present methods of tonometry are clinically sufficient to form an opinion about the diagnosis and also about the success of our treatment, the aim of which is to normalize the pressure through the 24 hours below 20 mm Hg."} {"id": "PMID:1267301", "title": "[Corticosteroids in viral hepatitis (author's transl)].", "content": "138 cases of viral hepatitis were selected among 27,000 pediatric clinical records corresponding to the years 1965-75. The clinical course of patients receiving corticosteroids during the acute phase was compared to that of the remaining patients, and an increased number of prolonged course cases was observed. At the same time, more frequent evolution to either aggressive forms or cirrhosis is suggested. Therefore, the authors discourage the use of corticosteroids in the treatment of common viral hepatitis.", "contents": "[Corticosteroids in viral hepatitis (author's transl)]. 138 cases of viral hepatitis were selected among 27,000 pediatric clinical records corresponding to the years 1965-75. The clinical course of patients receiving corticosteroids during the acute phase was compared to that of the remaining patients, and an increased number of prolonged course cases was observed. At the same time, more frequent evolution to either aggressive forms or cirrhosis is suggested. Therefore, the authors discourage the use of corticosteroids in the treatment of common viral hepatitis."} {"id": "PMID:1267314", "title": "Bias of the cover test in the diagnosis of alternating tropia.", "content": "In the evaluation of patients with alternating tropia, all errors tends to falsely overclassify the fixation pattern as free alternation and underestimate monocular fixation. This bias is particularly undesirable in infants when the cover test is used because more direct measurements of visual acuity are not possible.", "contents": "Bias of the cover test in the diagnosis of alternating tropia. In the evaluation of patients with alternating tropia, all errors tends to falsely overclassify the fixation pattern as free alternation and underestimate monocular fixation. This bias is particularly undesirable in infants when the cover test is used because more direct measurements of visual acuity are not possible."} {"id": "PMID:1267315", "title": "Change in weight of the human lens with age.", "content": "When data in the literature are pooled, a large number of points become available for plotting the weight of the human lens as a function of age. Between mean ages 15 and 85 years, the values are described by L = 1.32 A + 141, where L is the Lens weight in mg and A is the age in years. The correlation coefficient was 0.977. There thus appears to be a continual, linear increase in the weight of the lens with age.", "contents": "Change in weight of the human lens with age. When data in the literature are pooled, a large number of points become available for plotting the weight of the human lens as a function of age. Between mean ages 15 and 85 years, the values are described by L = 1.32 A + 141, where L is the Lens weight in mg and A is the age in years. The correlation coefficient was 0.977. There thus appears to be a continual, linear increase in the weight of the lens with age."} {"id": "PMID:1267316", "title": "X-linked congenital nystagmus: a problem in genetic counseling.", "content": "A pedigree with X-linked congenital nystagmus is presented. A mother wished information about prenatal sex determination. The large number of clinically affected female heterozygotes in the pedigree illustrates a potential problem in genetic counseling for this condition and possibly other X-linked disorders which affect the eye.", "contents": "X-linked congenital nystagmus: a problem in genetic counseling. A pedigree with X-linked congenital nystagmus is presented. A mother wished information about prenatal sex determination. The large number of clinically affected female heterozygotes in the pedigree illustrates a potential problem in genetic counseling for this condition and possibly other X-linked disorders which affect the eye."} {"id": "PMID:1267317", "title": "Topical epinephrine and cystoid macular edema.", "content": "Epinephrine maculopathy occurred in one eye of a patient that spontaneously developed intraretinal cystic maculopathy in the other eye. The clinical and fluorescein angiographic apperance of the two conditions were identical. It is likely that the two conditions have a common organic denominator.", "contents": "Topical epinephrine and cystoid macular edema. Epinephrine maculopathy occurred in one eye of a patient that spontaneously developed intraretinal cystic maculopathy in the other eye. The clinical and fluorescein angiographic apperance of the two conditions were identical. It is likely that the two conditions have a common organic denominator."} {"id": "PMID:1267318", "title": "Tobacco smoking and glaucoma.", "content": "Effect of cigarette smoking on aqueous humor dynamics in 70 normal males and 70 primary glaucoma patients was studied. A rise of intraocular tension of more than 5 mm after last puff of cigarette was taken as a positive result. It was observed that this test was positive in 37.1% of primary glaucoma patients and only in 11.4% in normal persons--a statistically significant difference. Cigarette smoking causes vasoconstriction and may be leading to rise in episcleral venous pressure and thus inhibiting aquenous outflow from the angle. This test can be used as a provocative test for primary glaucoma patients.", "contents": "Tobacco smoking and glaucoma. Effect of cigarette smoking on aqueous humor dynamics in 70 normal males and 70 primary glaucoma patients was studied. A rise of intraocular tension of more than 5 mm after last puff of cigarette was taken as a positive result. It was observed that this test was positive in 37.1% of primary glaucoma patients and only in 11.4% in normal persons--a statistically significant difference. Cigarette smoking causes vasoconstriction and may be leading to rise in episcleral venous pressure and thus inhibiting aquenous outflow from the angle. This test can be used as a provocative test for primary glaucoma patients."} {"id": "PMID:1267319", "title": "Vitreous fluidity in myopia.", "content": "Forth-eight eyes were examined to determine if degeneration and liquification of the vitreous could be determined by vitreous movement in subjects with myopia compared with subjects who had either emmetropia or hypermetropia. The difference in duration of vitreous movement for the myopes was significantly greater than that for nonmyopes (p less than 0.05).", "contents": "Vitreous fluidity in myopia. Forth-eight eyes were examined to determine if degeneration and liquification of the vitreous could be determined by vitreous movement in subjects with myopia compared with subjects who had either emmetropia or hypermetropia. The difference in duration of vitreous movement for the myopes was significantly greater than that for nonmyopes (p less than 0.05)."} {"id": "PMID:1267321", "title": "Silicone intubation of the lacrimal system: pitfalls, problems and complications.", "content": "The Quickert-Dryden method of silicone intubation of the lacrimal system has been modified to make it easier to perform and to avoid postoperative complications encountered by me during my experiences with 23 patients. Problems with the technique are identified and management of complications is discussed.", "contents": "Silicone intubation of the lacrimal system: pitfalls, problems and complications. The Quickert-Dryden method of silicone intubation of the lacrimal system has been modified to make it easier to perform and to avoid postoperative complications encountered by me during my experiences with 23 patients. Problems with the technique are identified and management of complications is discussed."} {"id": "PMID:1267322", "title": "Injected mixture for hemostasis in dacryocystorhinostomy.", "content": "A mixture of epinephrine and hyaluronidase, injected into the naso-orbital recess at the start of dacryocystorhinostomy and into the nasal mucosa immediately after bone penetration, appears to have a greater hemostatic effect than epinephrine alone. Surgical time is shortened by the reduced need for angular vessel ligation, suction, cautery of bleeding, and nasal packing. Postoperative ecchymosis and nasal clotting are also reduced.", "contents": "Injected mixture for hemostasis in dacryocystorhinostomy. A mixture of epinephrine and hyaluronidase, injected into the naso-orbital recess at the start of dacryocystorhinostomy and into the nasal mucosa immediately after bone penetration, appears to have a greater hemostatic effect than epinephrine alone. Surgical time is shortened by the reduced need for angular vessel ligation, suction, cautery of bleeding, and nasal packing. Postoperative ecchymosis and nasal clotting are also reduced."} {"id": "PMID:1267323", "title": "Histopathological observations of presbycusis.", "content": "Temporal bone histopathology of 17 aged patients who had spontaneous and gradually progressive bilateral sensorineural hearing losses associated with aging was studied. Six cases in the present material showed the gradually sloping audiometric curve; nine cases, abrupt high tone hearing loss; and two cases, the flat audiometric curve. The most prominent histopathological change in the inner ear was a decrease in the population of the spiral ganglion cells. However, diffuse senile atrophy was also often seen in the organ of Corti and the stria vascularis. A positive correlation between the degree of artheriosclerosis and the degree of sensorineural degeneration in the cochlea was not obtained in the present cases. Also, the correlation was not found to be consistent between the type of the audiometric curve and the localization of lesions in the sensory, the neural or the vascular elements in the cochlea. Our observations show that a certain type of audiometric curve does not necessarily indicate a lesion in a specific cochlear element.", "contents": "Histopathological observations of presbycusis. Temporal bone histopathology of 17 aged patients who had spontaneous and gradually progressive bilateral sensorineural hearing losses associated with aging was studied. Six cases in the present material showed the gradually sloping audiometric curve; nine cases, abrupt high tone hearing loss; and two cases, the flat audiometric curve. The most prominent histopathological change in the inner ear was a decrease in the population of the spiral ganglion cells. However, diffuse senile atrophy was also often seen in the organ of Corti and the stria vascularis. A positive correlation between the degree of artheriosclerosis and the degree of sensorineural degeneration in the cochlea was not obtained in the present cases. Also, the correlation was not found to be consistent between the type of the audiometric curve and the localization of lesions in the sensory, the neural or the vascular elements in the cochlea. Our observations show that a certain type of audiometric curve does not necessarily indicate a lesion in a specific cochlear element."} {"id": "PMID:1267324", "title": "Correlation of tubal function and volume of mastoid and middle ear space as related to otitis media.", "content": "In 69 ears with chronic otitis media and nine ears with traumatic perforations tubal function the size of the mastoid air cell system measured planimetrically on roentgenograms and the functional volume of the air filled ear spaces were studied for any correlations. The roentgenographic area and the functional volume were also studied for any variation in the duration of the disease. A correlation was found between abnormally small volumes and impaired tubal function, probably due to mucosal damage of the whole system, i.e. Eustachian tube, middle ear and mastoid air cells. No such association was found between area and tubal function. The volume, but not the area, decrease with the duration of the disease.", "contents": "Correlation of tubal function and volume of mastoid and middle ear space as related to otitis media. In 69 ears with chronic otitis media and nine ears with traumatic perforations tubal function the size of the mastoid air cell system measured planimetrically on roentgenograms and the functional volume of the air filled ear spaces were studied for any correlations. The roentgenographic area and the functional volume were also studied for any variation in the duration of the disease. A correlation was found between abnormally small volumes and impaired tubal function, probably due to mucosal damage of the whole system, i.e. Eustachian tube, middle ear and mastoid air cells. No such association was found between area and tubal function. The volume, but not the area, decrease with the duration of the disease."} {"id": "PMID:1267325", "title": "Spastic dysphonia.", "content": "130 cases of spastic dysphonia are reviewed with special emphasis on the etiology of the disorder. An analysis of the circumstances surrounding the onset of the disease points strongly to a psychogenic origin of the disease in, at least, the vast majority of the cases.", "contents": "Spastic dysphonia. 130 cases of spastic dysphonia are reviewed with special emphasis on the etiology of the disorder. An analysis of the circumstances surrounding the onset of the disease points strongly to a psychogenic origin of the disease in, at least, the vast majority of the cases."} {"id": "PMID:1267326", "title": "Schwannoma of the jugular foramen.", "content": "Two cases of schwannoma limited to the jugular foramen are described. This entity may clinically and radiologically resemble glomus jugulare tumors so closely, that only careful histological examination of an adequate surgical tumor specimen can provide a definitive diagnosis. Since documentation of this form of neurogenic tumor is lacking in the literature, it suggests that the entity is very rare or that such tumors may be erroneously classified as glomus jugulare tumors. The two cases in this study were managed surgically by subtotal removal via a wide transmastoid approach.", "contents": "Schwannoma of the jugular foramen. Two cases of schwannoma limited to the jugular foramen are described. This entity may clinically and radiologically resemble glomus jugulare tumors so closely, that only careful histological examination of an adequate surgical tumor specimen can provide a definitive diagnosis. Since documentation of this form of neurogenic tumor is lacking in the literature, it suggests that the entity is very rare or that such tumors may be erroneously classified as glomus jugulare tumors. The two cases in this study were managed surgically by subtotal removal via a wide transmastoid approach."} {"id": "PMID:1267327", "title": "Delineation of cochlear glycogen by electron microscopy.", "content": "Two techniques for the demonstration and identification of glycogen by electron microscopy were applied to the cochlear duct tissues of normal guinea pigs and chinchillas. A modified osmium tetroxide fixative (with potassium ferricyanide) has been described by De Bruijn to selectively stain the glycogen particle. Identification of the stained particle was effected by its selective removal from the tissue with amyloglucosidase, an enzyme specific in its degradation of the glycogen molecule. Glycogen particles were noted in several cell types within the cochlear duct, but concentrations were greater in outer hair cells of both species and in the stria vascularis of the chinchilla. The fact that amyloglucosidase completely eliminated these particles from the liver of both species as well as cochlear tissue, led to the conclusion that these particles are indeed glycogen.", "contents": "Delineation of cochlear glycogen by electron microscopy. Two techniques for the demonstration and identification of glycogen by electron microscopy were applied to the cochlear duct tissues of normal guinea pigs and chinchillas. A modified osmium tetroxide fixative (with potassium ferricyanide) has been described by De Bruijn to selectively stain the glycogen particle. Identification of the stained particle was effected by its selective removal from the tissue with amyloglucosidase, an enzyme specific in its degradation of the glycogen molecule. Glycogen particles were noted in several cell types within the cochlear duct, but concentrations were greater in outer hair cells of both species and in the stria vascularis of the chinchilla. The fact that amyloglucosidase completely eliminated these particles from the liver of both species as well as cochlear tissue, led to the conclusion that these particles are indeed glycogen."} {"id": "PMID:1267328", "title": "Effect of nicotine on cochlear function and noise-induced hair cell loss.", "content": "Nicotine administered in high doses intravenously (1 mg/kg) and intracochlearly (10 mM) exhibited very little effect on guinea pig cochlear potentials. When administered chronically (1-20 mg/kg, i.p. for 20 days), nicotine demonstrated no effect on cochlear potentials or the number of observed hair cell scars monitored 21 days after the treatment was terminated. Neither chronic nicotine treatment (1-20 mg/kg, i.p. for 20 days) nor acute reserpine pretreatment (5 mg/kg, i.p. 24 hours before) altered the hair cell damaging effects of an intense pure tone (4 kHz, 126 dB SPL, 30 min). No nicotine ototoxicity was detected by the methods used in this study.", "contents": "Effect of nicotine on cochlear function and noise-induced hair cell loss. Nicotine administered in high doses intravenously (1 mg/kg) and intracochlearly (10 mM) exhibited very little effect on guinea pig cochlear potentials. When administered chronically (1-20 mg/kg, i.p. for 20 days), nicotine demonstrated no effect on cochlear potentials or the number of observed hair cell scars monitored 21 days after the treatment was terminated. Neither chronic nicotine treatment (1-20 mg/kg, i.p. for 20 days) nor acute reserpine pretreatment (5 mg/kg, i.p. 24 hours before) altered the hair cell damaging effects of an intense pure tone (4 kHz, 126 dB SPL, 30 min). No nicotine ototoxicity was detected by the methods used in this study."} {"id": "PMID:1267329", "title": "Auditory imperception.", "content": "The diagnosis, evaluation and treatment of learning disabilities involves many disciplines. The Otolaryngologist can play an important role in reducing the psychosocial-educational effects of perceptual hanicaps by being active in early diagnosis. This paper presents: 1) an overview of significant information pertaining to auditory perceptual problems and 2) suggestions for the clinican interested in identifying children with auditory perceptual defects.", "contents": "Auditory imperception. The diagnosis, evaluation and treatment of learning disabilities involves many disciplines. The Otolaryngologist can play an important role in reducing the psychosocial-educational effects of perceptual hanicaps by being active in early diagnosis. This paper presents: 1) an overview of significant information pertaining to auditory perceptual problems and 2) suggestions for the clinican interested in identifying children with auditory perceptual defects."} {"id": "PMID:1267330", "title": "Caloric-eye tracking pattern test: I. Visual suppression and the possibility of simplified differential diagnosis between peripheral and central vertigo.", "content": "During the examination of patients who complain of vertigo or who have equilibrium disorders, it is often difficult to determine the etiology of the disorders, that is, to determine whether it is dependent on a peripheral or central vestibular disorder. To attempt to guess the etiology in these cases, we devised a new method: the caloric eye-tracking pattern test. In normal subjects and in patients with peripheral disorders, as is well known, caloric nystagmus has little influence on the eye-tracking pattern. In contrast, in patients with central vestibular disorders, caloric nystagmus evoked abnormalities on the eye-tracking pattern, either superimposed or saccades, in spite of the fact that the eye-tracking pattern before the caloric stimulation is normal. These findings result from the visual suppression mechanism to the vestibular nystagmus. We can say that the visual suppression to the vestibular nystagmus is evoked more strongly bu pursuing a moving visual stimulus than by gazing at a stationary target. These results are interesting, not only form the physiological view point, but also from the clinical view point. There is a possibility of the differential diagnosis between peripheral and central vertigo.", "contents": "Caloric-eye tracking pattern test: I. Visual suppression and the possibility of simplified differential diagnosis between peripheral and central vertigo. During the examination of patients who complain of vertigo or who have equilibrium disorders, it is often difficult to determine the etiology of the disorders, that is, to determine whether it is dependent on a peripheral or central vestibular disorder. To attempt to guess the etiology in these cases, we devised a new method: the caloric eye-tracking pattern test. In normal subjects and in patients with peripheral disorders, as is well known, caloric nystagmus has little influence on the eye-tracking pattern. In contrast, in patients with central vestibular disorders, caloric nystagmus evoked abnormalities on the eye-tracking pattern, either superimposed or saccades, in spite of the fact that the eye-tracking pattern before the caloric stimulation is normal. These findings result from the visual suppression mechanism to the vestibular nystagmus. We can say that the visual suppression to the vestibular nystagmus is evoked more strongly bu pursuing a moving visual stimulus than by gazing at a stationary target. These results are interesting, not only form the physiological view point, but also from the clinical view point. There is a possibility of the differential diagnosis between peripheral and central vertigo."} {"id": "PMID:1267331", "title": "Effect of anesthesia on susceptibility to acoustic trauma.", "content": "In an effort to ascertain whether differences in susceptibility to noise depend on general condition, awake and anesthetized guinea pigs were given a 4 kHz pure tone overstimulation under identical conditions. Cochlear hair cells were histologically examined four weeks after the noise exposure. The damage was localized in the upper part of the first turn and the lower part of the second turn. One fourth as much damage occurred in the anesthetized group. The distribution of damage in the four rows of sensory cells was different in the two experimental groups. In both groups of animals the damage was localized mainly to the outer hair cells, the first row sustaining the major damage.", "contents": "Effect of anesthesia on susceptibility to acoustic trauma. In an effort to ascertain whether differences in susceptibility to noise depend on general condition, awake and anesthetized guinea pigs were given a 4 kHz pure tone overstimulation under identical conditions. Cochlear hair cells were histologically examined four weeks after the noise exposure. The damage was localized in the upper part of the first turn and the lower part of the second turn. One fourth as much damage occurred in the anesthetized group. The distribution of damage in the four rows of sensory cells was different in the two experimental groups. In both groups of animals the damage was localized mainly to the outer hair cells, the first row sustaining the major damage."} {"id": "PMID:1267332", "title": "Polygenic inheritance of otosclerosis.", "content": "A large family has been studied and its pedigree traced for six generations. Fifteen relatives are known to have had otosclerosis. Of these, the only six individuals who developed this disease before the age of twenty were offspring of second-cousin marriages. Other children in the extended family developed the disease later and may have had somewhat less severe symptoms. The original hypothesis that the severe, early onset cases occurred among those homozygous for a monogenic trait became improbable on mathematical analysis. We conclude that the inheritance of otosclerosis in this family is polygenic and probably multifactorial. Individuals marrying within the family have a greatly increased risk of giving birth to children who will develop otosclerosis early, and perhaps severly. Those who marry outside the family have a greatly decreased risk. They do, of course have a higher risk than the general population of having children who will at some point experience a conductive hearing loss.", "contents": "Polygenic inheritance of otosclerosis. A large family has been studied and its pedigree traced for six generations. Fifteen relatives are known to have had otosclerosis. Of these, the only six individuals who developed this disease before the age of twenty were offspring of second-cousin marriages. Other children in the extended family developed the disease later and may have had somewhat less severe symptoms. The original hypothesis that the severe, early onset cases occurred among those homozygous for a monogenic trait became improbable on mathematical analysis. We conclude that the inheritance of otosclerosis in this family is polygenic and probably multifactorial. Individuals marrying within the family have a greatly increased risk of giving birth to children who will develop otosclerosis early, and perhaps severly. Those who marry outside the family have a greatly decreased risk. They do, of course have a higher risk than the general population of having children who will at some point experience a conductive hearing loss."} {"id": "PMID:1267333", "title": "Adenocarcinoma originating in the thyroglossal duct.", "content": "Eighty-six cases of carcinoma of the thyroglossal duct have been reported in the literature, most of these being well-differentiated adenocarcinomas. Three new cases of the latter type are presented. Cases where carcinoma of the thyroglossal duct is suspected should be investigated with fine-needle biopsy, thyroid scintigraphy, skeletal and pulmonary X-ray, determination of TSH, T 3, PBI and blood serum calcium. The treatment of well-differentiated adenocarcinomas is a combination of surgical and medical procedures.", "contents": "Adenocarcinoma originating in the thyroglossal duct. Eighty-six cases of carcinoma of the thyroglossal duct have been reported in the literature, most of these being well-differentiated adenocarcinomas. Three new cases of the latter type are presented. Cases where carcinoma of the thyroglossal duct is suspected should be investigated with fine-needle biopsy, thyroid scintigraphy, skeletal and pulmonary X-ray, determination of TSH, T 3, PBI and blood serum calcium. The treatment of well-differentiated adenocarcinomas is a combination of surgical and medical procedures."} {"id": "PMID:1267335", "title": "Protein and cellular pattern of glue ear secretions.", "content": "Analysis of glue ear secretions showed that the total protein content was slightly higher than in serum and that in the effusion proteins appeared that were specific to the mucosal secretion. The cellular analysis of samples from 137 ears showed that lymphocytes and neutrophils predominated, and that monocytes and phagocytes appeared in most specimens. Eosinophils and mast cells were rare. Staining of bacteria in the smear was seen in one-third of the slides and the mucus strands were numerous. The cellular picture is in line with an infective etiology.", "contents": "Protein and cellular pattern of glue ear secretions. Analysis of glue ear secretions showed that the total protein content was slightly higher than in serum and that in the effusion proteins appeared that were specific to the mucosal secretion. The cellular analysis of samples from 137 ears showed that lymphocytes and neutrophils predominated, and that monocytes and phagocytes appeared in most specimens. Eosinophils and mast cells were rare. Staining of bacteria in the smear was seen in one-third of the slides and the mucus strands were numerous. The cellular picture is in line with an infective etiology."} {"id": "PMID:1267336", "title": "Immunoglobulin E in chronic middle ear effusions.", "content": "A total of 61 middle ear effusions and matched sera obtained from patients suffering from chronic otitis media with effusions (OME) was examined for IgE and other immunoglobulins to see if a reaginic antibody is involved in OME. The IgE levels were determined by the Phadebas IgE radioimmunoassay test. Excluding one patient who had extremely high IgE as a result of parasitosis, there were only three cases which showed marginally increased serum IgE levels. Elevated IgE levels in sera and/or in effusions were unrelated to a history of allergy. The mucoid effusions had significantly higher effusion levels than the levels in corresponding sera (p less than .0005). Fourteen percent of the cases examined showed effusion IgE levels five times or more higher than serum levels. Biopsy specimens of these patients showed numerous degranulating mast cells. Only two specimens showed eosinophilic infiltration. It is suggested that the IgE is produced locally by the mucosa in mucoid-type effusions and may have been involved in mast cell degranulation. However, this study cannot confirm the allergic nature of the OME.", "contents": "Immunoglobulin E in chronic middle ear effusions. A total of 61 middle ear effusions and matched sera obtained from patients suffering from chronic otitis media with effusions (OME) was examined for IgE and other immunoglobulins to see if a reaginic antibody is involved in OME. The IgE levels were determined by the Phadebas IgE radioimmunoassay test. Excluding one patient who had extremely high IgE as a result of parasitosis, there were only three cases which showed marginally increased serum IgE levels. Elevated IgE levels in sera and/or in effusions were unrelated to a history of allergy. The mucoid effusions had significantly higher effusion levels than the levels in corresponding sera (p less than .0005). Fourteen percent of the cases examined showed effusion IgE levels five times or more higher than serum levels. Biopsy specimens of these patients showed numerous degranulating mast cells. Only two specimens showed eosinophilic infiltration. It is suggested that the IgE is produced locally by the mucosa in mucoid-type effusions and may have been involved in mast cell degranulation. However, this study cannot confirm the allergic nature of the OME."} {"id": "PMID:1267337", "title": "Antimicrobial factors and bacterial correlation in chronic otitis media with effusion.", "content": "Analyses of effusions and sera from patients with otitis media with effusion demonstrated local production in the middle ear of lysozyme, IgA and IgG. The effusion IgM was markedly elevated in some patients, also indicating local production. Complement C3 with rare exception was significantly lower in effusions than sera, suggesting utilization of complement in the middle ear, perhaps in conjunction with antibodies. The presence of high levels of lysozyme and immunoglobulins in effusions correlates with the low isolation rate of microorganisms in culture and may influence survival of organisms in the middle ear.", "contents": "Antimicrobial factors and bacterial correlation in chronic otitis media with effusion. Analyses of effusions and sera from patients with otitis media with effusion demonstrated local production in the middle ear of lysozyme, IgA and IgG. The effusion IgM was markedly elevated in some patients, also indicating local production. Complement C3 with rare exception was significantly lower in effusions than sera, suggesting utilization of complement in the middle ear, perhaps in conjunction with antibodies. The presence of high levels of lysozyme and immunoglobulins in effusions correlates with the low isolation rate of microorganisms in culture and may influence survival of organisms in the middle ear."} {"id": "PMID:1267338", "title": "Classification of middle ear effusions.", "content": "Proper use of terminology and classification of various categories of effusion throughout the world is necessary if we are to obtain dissemination of pertinent scientific and clinical information and to make progress in understanding and eradicating this widespread group of diseases. The general term, middle ear effusion, and the categories serous, mucoid, and purulent are suggested to describe collections of fluid in the middle ear; the use of other descriptive terms should be influenced by the nature of the clinical, cytologic, bacteriologic, histopathologic and chemical findings in the fluid and lining membrane of the middle ear.", "contents": "Classification of middle ear effusions. Proper use of terminology and classification of various categories of effusion throughout the world is necessary if we are to obtain dissemination of pertinent scientific and clinical information and to make progress in understanding and eradicating this widespread group of diseases. The general term, middle ear effusion, and the categories serous, mucoid, and purulent are suggested to describe collections of fluid in the middle ear; the use of other descriptive terms should be influenced by the nature of the clinical, cytologic, bacteriologic, histopathologic and chemical findings in the fluid and lining membrane of the middle ear."} {"id": "PMID:1267339", "title": "Microbiology in serous otitis media.", "content": "It is now established that serous otitis media (SOM) is an inflammatory reaction of the mucosa of the middle ear. A number of microbiological factors are contributory causes. It is clear, among other things, that the microbiologic environment in the nasopharynx in SOM is the same as that in acute otitis media. Neither adenoidectomy and tonsillectomy nor treatiment with conventional chemotherapeutics has proved effective for eradicating pathogenic bacteria from the nasopharynx. Intense research to find new antibiotics and effective means may be one way of getting us out of our present therapeutic dilemma. Other possibilities are to try to produce polyvalent bacterial vaccines and to increase our knowledge of the immunology of the nasopharynx.", "contents": "Microbiology in serous otitis media. It is now established that serous otitis media (SOM) is an inflammatory reaction of the mucosa of the middle ear. A number of microbiological factors are contributory causes. It is clear, among other things, that the microbiologic environment in the nasopharynx in SOM is the same as that in acute otitis media. Neither adenoidectomy and tonsillectomy nor treatiment with conventional chemotherapeutics has proved effective for eradicating pathogenic bacteria from the nasopharynx. Intense research to find new antibiotics and effective means may be one way of getting us out of our present therapeutic dilemma. Other possibilities are to try to produce polyvalent bacterial vaccines and to increase our knowledge of the immunology of the nasopharynx."} {"id": "PMID:1267340", "title": "Physiology of the Eustachian tube.", "content": "A method for studying the middle ear mechanics is described. The method permits continuous recording of the volume deviation of the drum in relation to the neutral position, both on change in the ambient pressure and in the pressure in the middle ear. One hundred and two volunteers with normal hearing, i.e., a normal audiogram and normal ear findings, were tested repeatedly. This is the most detailed and extensive investigation hitherto performed on healthy volunteers with the aid of a sophisticated, reliable scientific method not suitable for clinical use.", "contents": "Physiology of the Eustachian tube. A method for studying the middle ear mechanics is described. The method permits continuous recording of the volume deviation of the drum in relation to the neutral position, both on change in the ambient pressure and in the pressure in the middle ear. One hundred and two volunteers with normal hearing, i.e., a normal audiogram and normal ear findings, were tested repeatedly. This is the most detailed and extensive investigation hitherto performed on healthy volunteers with the aid of a sophisticated, reliable scientific method not suitable for clinical use."} {"id": "PMID:1267341", "title": "Normal gas exchange in the human middle ear.", "content": "Different kinds of biological gas pockets and the special character of the middle ear as a gas pocket are discussed. The pattern of gas absorption from the normal middle ear and from ears with blocked Eustachian tubes is presented. The amount of gas leaving the ear by diffusion and the resulting underpressure from this process are determined. The composition of air in the ear is compared to that in experimental gas pockets and the role of the partial pressures of CO2 and O2 in secretory otitis media is discussed.", "contents": "Normal gas exchange in the human middle ear. Different kinds of biological gas pockets and the special character of the middle ear as a gas pocket are discussed. The pattern of gas absorption from the normal middle ear and from ears with blocked Eustachian tubes is presented. The amount of gas leaving the ear by diffusion and the resulting underpressure from this process are determined. The composition of air in the ear is compared to that in experimental gas pockets and the role of the partial pressures of CO2 and O2 in secretory otitis media is discussed."} {"id": "PMID:1267342", "title": "Study of the ventilation of middle ear using radioactive xenon.", "content": "The greatest contribution of nuclear medicine has been to make possible dynamic measurements of regional function. It is conceivable that if this technology could be successfully used to measure the ventilation and clearance of the middle ear, answers to some of the most crucial problems in otology may be found. The objectives of this paper are three-fold: 1) A descriptive account of radiotracers and radiodetectors with emphasis on Xenon133. 2) The development of scintillographic techniques for the dynamic study of the ventilation of the ear and sinuses. 3) The methods that are being explored for the quantification of these functions.", "contents": "Study of the ventilation of middle ear using radioactive xenon. The greatest contribution of nuclear medicine has been to make possible dynamic measurements of regional function. It is conceivable that if this technology could be successfully used to measure the ventilation and clearance of the middle ear, answers to some of the most crucial problems in otology may be found. The objectives of this paper are three-fold: 1) A descriptive account of radiotracers and radiodetectors with emphasis on Xenon133. 2) The development of scintillographic techniques for the dynamic study of the ventilation of the ear and sinuses. 3) The methods that are being explored for the quantification of these functions."} {"id": "PMID:1267344", "title": "Eustachian tube ventilatory function in children.", "content": "In order to establish a simple stimulus-response characteristic of Eustachian tube physiology in children, the tubal ventilatory function was studied. The parameters of active and passive opening of the tube were measured for three groups of patients with nonintact tympanic membranes. The group with traumatic perforations of the tympanic membrane without any history of middle ear disease had better active equilibration function than the group with chronic otitis media and perforations of the tympanic membrane and the group with tympanostomy tubes in the tympanic membrane. Quantitatively, this could be expressed in terms of residual positive pressures. In the study of repeated inflation of the middle ear, all groups had lower second opening pressures which are attributed to the effect of surface forces.", "contents": "Eustachian tube ventilatory function in children. In order to establish a simple stimulus-response characteristic of Eustachian tube physiology in children, the tubal ventilatory function was studied. The parameters of active and passive opening of the tube were measured for three groups of patients with nonintact tympanic membranes. The group with traumatic perforations of the tympanic membrane without any history of middle ear disease had better active equilibration function than the group with chronic otitis media and perforations of the tympanic membrane and the group with tympanostomy tubes in the tympanic membrane. Quantitatively, this could be expressed in terms of residual positive pressures. In the study of repeated inflation of the middle ear, all groups had lower second opening pressures which are attributed to the effect of surface forces."} {"id": "PMID:1267345", "title": "Middle ear ventilation in secretory otitis media.", "content": "The Eustachian tube function was determined repeatedly in 42 patients during as well as after the course of secretory otitis media. Air pressure equalization technique and impedance audiometry were used. Also the size of the mastoid air cell system was determined. It was found that poor tubal function and a small mastoid air cell system are signficance findings in these ears.", "contents": "Middle ear ventilation in secretory otitis media. The Eustachian tube function was determined repeatedly in 42 patients during as well as after the course of secretory otitis media. Air pressure equalization technique and impedance audiometry were used. Also the size of the mastoid air cell system was determined. It was found that poor tubal function and a small mastoid air cell system are signficance findings in these ears."} {"id": "PMID:1267346", "title": "Concepts on the pathogenesis of middle ear effusions.", "content": "Several concepts related to the pathogenesis of middle ear effusions are postulated. The mechanisms proposed are based on an understanding of fluid mechanics. A flask with a long, narrow neck is presented as a model of the Eustachian tube-middle ear-mastoid system. Fluid flow into and out of the flask is dependent upon the pressure gradient, compliance of the narrow neck and whether or not the bulbous portion is intact. It is suggested that locking of the tube may be dependent upon the speed of the application of the negative pressure and the compliance. Eustachian tube opening appears to be related not only to active muscle forces but may also be dependent upon the presence of a pressure gradient which passively assists tubal function. It is proposed that middle ear effusions result from reflux, aspiration or insufflation of nasopharyngeal secretions (acute otitis media), or from persistent functional or mechanical Eustachian tube obstruction (secretory otitis media) or both.", "contents": "Concepts on the pathogenesis of middle ear effusions. Several concepts related to the pathogenesis of middle ear effusions are postulated. The mechanisms proposed are based on an understanding of fluid mechanics. A flask with a long, narrow neck is presented as a model of the Eustachian tube-middle ear-mastoid system. Fluid flow into and out of the flask is dependent upon the pressure gradient, compliance of the narrow neck and whether or not the bulbous portion is intact. It is suggested that locking of the tube may be dependent upon the speed of the application of the negative pressure and the compliance. Eustachian tube opening appears to be related not only to active muscle forces but may also be dependent upon the presence of a pressure gradient which passively assists tubal function. It is proposed that middle ear effusions result from reflux, aspiration or insufflation of nasopharyngeal secretions (acute otitis media), or from persistent functional or mechanical Eustachian tube obstruction (secretory otitis media) or both."} {"id": "PMID:1267348", "title": "Pediatrician's view of middle ear effusions: more questions than answers.", "content": "Although middle ear effusion is the most common of the chronic conditions encountered in pediatric practice, it frequently goes unrecognized, and relatively little is known about its epidemiology or its natural history. More importantly, the impact of middle ear effusion on the overall well-being of infants and children, and on their cognitive and language development, remains essentially unexplored. In part because of these gaps in our knowledge, and also because prospective, controlled treatment trials have not been reported, uncertainty and controversy exist concerning: 1) the necessity, in many instances, of treating middle ear effusion; 2) the choice of various treatment methods; and 3) the timing of those treatments that are undertaken. Finally, the widespread use of adenoidectomy to prevent middle ear inflammation is seriously lacking in supporting evidence. A few reported studies bear on some of these questions, but both their scope and the information they provide are limited. In order to resolve important prognostic and treatment issues concerning middle ear effusion during infancy and childhood, carefully designed epidemiologic and clinical studies of types not hitherto reported are urgently needed.", "contents": "Pediatrician's view of middle ear effusions: more questions than answers. Although middle ear effusion is the most common of the chronic conditions encountered in pediatric practice, it frequently goes unrecognized, and relatively little is known about its epidemiology or its natural history. More importantly, the impact of middle ear effusion on the overall well-being of infants and children, and on their cognitive and language development, remains essentially unexplored. In part because of these gaps in our knowledge, and also because prospective, controlled treatment trials have not been reported, uncertainty and controversy exist concerning: 1) the necessity, in many instances, of treating middle ear effusion; 2) the choice of various treatment methods; and 3) the timing of those treatments that are undertaken. Finally, the widespread use of adenoidectomy to prevent middle ear inflammation is seriously lacking in supporting evidence. A few reported studies bear on some of these questions, but both their scope and the information they provide are limited. In order to resolve important prognostic and treatment issues concerning middle ear effusion during infancy and childhood, carefully designed epidemiologic and clinical studies of types not hitherto reported are urgently needed."} {"id": "PMID:1267349", "title": "Tympanometry: application and interpretation.", "content": "The poor relationship between hearing loss and ear disease minimizes the effectiveness of audiometry as a technique for the identification of middle ear disorders. Tympanometry has been shown to be a highly sensitive technique for the identification of and differentiation between middle ear disorders. It is particularly useful in a pediatric population where ear disease is so frequently encountered. The interpretation of tympanometry on the basis of a descriptive analysis of tympanograms is proposed as opposed to a coded typing system. Descriptive analysis views the pathological effects of middle ear diseases on pressure peaks, amplitude and shape of tympanograms.", "contents": "Tympanometry: application and interpretation. The poor relationship between hearing loss and ear disease minimizes the effectiveness of audiometry as a technique for the identification of middle ear disorders. Tympanometry has been shown to be a highly sensitive technique for the identification of and differentiation between middle ear disorders. It is particularly useful in a pediatric population where ear disease is so frequently encountered. The interpretation of tympanometry on the basis of a descriptive analysis of tympanograms is proposed as opposed to a coded typing system. Descriptive analysis views the pathological effects of middle ear diseases on pressure peaks, amplitude and shape of tympanograms."} {"id": "PMID:1267347", "title": "Autonomic stimulation, osmolarity and prostaglandin effects in the Eustachian tube.", "content": "Stimulation of the vidian nerve in the dog induced an apparent vasodilation in the mucosa of the Eustachian tube. It is presumed that these parasympathetic fibers course from the greater petrosal nerve through the vidian to the sphenopalatine ganglion. The pharyngeal nerve arises from the ganglion and innervates the mucosa of the tube. Perfusion of the dog's Eustachian tube with solutions of various osmolarities caused a shrinking or swelling of the tube mucosa. Ten percent alterations in the concentration of saline, Ringer's or isotonic KCl produced a hypo- or hypertonic effect. Systemic administration of osmotic diuretics was shown to remove water from normal and edematous tubal mucosa. An agent in human middle ear effusions was found to contract smooth muscle. The behavior of this agent in pharmacological tests suggested the presence of prostaglandins (PG). The effusions were tested for the presence of other inflammatory mediators such as bradykinin, acetylcholine and histamine. These were felt to be absent or present in small amounts. A radioimmune assay of pooled samples of middle ear effusions revealed the presence of several PG, notably PGF2alpha and PGE2. There appeared to be a higher concentration of PG in mucoid effusions than serous effusions. The inflammatory capabilities of these agents are mentioned.", "contents": "Autonomic stimulation, osmolarity and prostaglandin effects in the Eustachian tube. Stimulation of the vidian nerve in the dog induced an apparent vasodilation in the mucosa of the Eustachian tube. It is presumed that these parasympathetic fibers course from the greater petrosal nerve through the vidian to the sphenopalatine ganglion. The pharyngeal nerve arises from the ganglion and innervates the mucosa of the tube. Perfusion of the dog's Eustachian tube with solutions of various osmolarities caused a shrinking or swelling of the tube mucosa. Ten percent alterations in the concentration of saline, Ringer's or isotonic KCl produced a hypo- or hypertonic effect. Systemic administration of osmotic diuretics was shown to remove water from normal and edematous tubal mucosa. An agent in human middle ear effusions was found to contract smooth muscle. The behavior of this agent in pharmacological tests suggested the presence of prostaglandins (PG). The effusions were tested for the presence of other inflammatory mediators such as bradykinin, acetylcholine and histamine. These were felt to be absent or present in small amounts. A radioimmune assay of pooled samples of middle ear effusions revealed the presence of several PG, notably PGF2alpha and PGE2. There appeared to be a higher concentration of PG in mucoid effusions than serous effusions. The inflammatory capabilities of these agents are mentioned."} {"id": "PMID:1267351", "title": "School screening for middle ear effusions.", "content": "Early detection of middle ear effusions is highly desirable not only from a medical standpoint, but also educationally, psychologically and socially. Present methods do not appear to be adequate and the proposal has been made that impedance measurement may be of greater effectiveness in detecting abnormalities of middle ear function. Eighty children have been studied over a period of six to seven years during which time the middle ear function has been monitored by means of an impedance meter. Approximately one-half of the children have not indicated any variation in middle ear function over the period of observation. About one-third of the children have had isolated episodes of effusion from which they have recovered spontaneously and without adverse effects. The remaining one-sixth have had repeated episodes of effusion or persistent middle ear malfunction for substantial periods of time. Observation of the middle ear muscle reflexes at suitably chosen time intervals appears to have promise as a method of early detection of effusion in the middle ear.", "contents": "School screening for middle ear effusions. Early detection of middle ear effusions is highly desirable not only from a medical standpoint, but also educationally, psychologically and socially. Present methods do not appear to be adequate and the proposal has been made that impedance measurement may be of greater effectiveness in detecting abnormalities of middle ear function. Eighty children have been studied over a period of six to seven years during which time the middle ear function has been monitored by means of an impedance meter. Approximately one-half of the children have not indicated any variation in middle ear function over the period of observation. About one-third of the children have had isolated episodes of effusion from which they have recovered spontaneously and without adverse effects. The remaining one-sixth have had repeated episodes of effusion or persistent middle ear malfunction for substantial periods of time. Observation of the middle ear muscle reflexes at suitably chosen time intervals appears to have promise as a method of early detection of effusion in the middle ear."} {"id": "PMID:1267352", "title": "Improved diagnosis of middle ear effusions employing the objective otoscope.", "content": "A new quantitative diagnostic otoscope presently under development supplements the conventional otoscopic examination with a quantitative pneumatic system and objective measurements derived from tympanometry. The instrument provides information to assist in the diagnosis of the presence of middle ear effusion (MEE), the middle ear pressure and tympanic membrane status during the visual examination. Uncertainty introduced by subjective judgement involved with traditional pneumatic otoscopy is eliminated enabling a more rapid and accurate diagnosis. Clinical evaluations were performed in which 92% accuracy was achieved for the diagnosis of the presence of MEE in 38 ears. The results were verified at myringotomy. The instrument is being designed for use by physicians and paraprofessionals.", "contents": "Improved diagnosis of middle ear effusions employing the objective otoscope. A new quantitative diagnostic otoscope presently under development supplements the conventional otoscopic examination with a quantitative pneumatic system and objective measurements derived from tympanometry. The instrument provides information to assist in the diagnosis of the presence of middle ear effusion (MEE), the middle ear pressure and tympanic membrane status during the visual examination. Uncertainty introduced by subjective judgement involved with traditional pneumatic otoscopy is eliminated enabling a more rapid and accurate diagnosis. Clinical evaluations were performed in which 92% accuracy was achieved for the diagnosis of the presence of MEE in 38 ears. The results were verified at myringotomy. The instrument is being designed for use by physicians and paraprofessionals."} {"id": "PMID:1267353", "title": "Cytologic and immunologic response revealed in middle ear effusions.", "content": "The cellular patterns of middle ear effusions which reveal lymphocytic transformation and macrophage activity, help to explain the basic pathologic condition. This appears to be a typical delayed-type hypersensitivity reaction. The nasal cytogram often contributes to the understanding of the aural pathology. The treatment must be individualized with an effort to find the source of antigenic stimulation causing the response, and, in turns, support the systemic immune system of the patient in definitive ways, as have been suggested.", "contents": "Cytologic and immunologic response revealed in middle ear effusions. The cellular patterns of middle ear effusions which reveal lymphocytic transformation and macrophage activity, help to explain the basic pathologic condition. This appears to be a typical delayed-type hypersensitivity reaction. The nasal cytogram often contributes to the understanding of the aural pathology. The treatment must be individualized with an effort to find the source of antigenic stimulation causing the response, and, in turns, support the systemic immune system of the patient in definitive ways, as have been suggested."} {"id": "PMID:1267350", "title": "Tympanometry revealing middle ear pathology.", "content": "In order to evaluate the usefulness of impedance audiometry as a screening method for school children, two different pilot studies were performed. The results indicated that impedance audiometry (tympanometry and stapedius reflex test) was more efficient than otoscopy and pure tone screening in the detection of ears with secretory otitis media (SOM). In order to gain some more experience, an extended study of 800 7-year-olds was performed. The results from this investigation showed 6.5% pathological values with pure tone screening, 13.5% pathological values with tympanometry and 32% elevated or nonelicitable stapedius reflexes. Analysis of our observations indicates that the stapedius reflex may be too sensitive a test to be used as a screening method. Tympanometry, however, is recommended as a complement to pure tone screening in screening of children. A 6-12 months follow-up was also performed on 357 ears in which an initial study had shown a middle ear pressure of less than or equal to -100 mm H2O. At the repeated test 20% had pathological pure tone screening, 40% had a middle ear pressure of less than or equal to -100 mm H2O, 57% had elevated or nonelicitable stapedius reflexes, and 14% had middle ear effusion. The high frequency of persisting abnormal middle ear pressure and effusion in these 357 ears suggests that a middle ear pressure of less than or equal to -100 mm H2O can be a predisposing factor for SOM. In an experimental study on human temporal bones it was demonstrated that the tympanogram preserves its original appearance when the water level is low in the middle ear, while a higher level gives rise to a pathological tympanogram. It is also demonstrated that there is a discrepancy between the tympanometrically, indirectly recorded middle ear pressure and the middle ear pressure as measured manometrically, directly from the middle ear.", "contents": "Tympanometry revealing middle ear pathology. In order to evaluate the usefulness of impedance audiometry as a screening method for school children, two different pilot studies were performed. The results indicated that impedance audiometry (tympanometry and stapedius reflex test) was more efficient than otoscopy and pure tone screening in the detection of ears with secretory otitis media (SOM). In order to gain some more experience, an extended study of 800 7-year-olds was performed. The results from this investigation showed 6.5% pathological values with pure tone screening, 13.5% pathological values with tympanometry and 32% elevated or nonelicitable stapedius reflexes. Analysis of our observations indicates that the stapedius reflex may be too sensitive a test to be used as a screening method. Tympanometry, however, is recommended as a complement to pure tone screening in screening of children. A 6-12 months follow-up was also performed on 357 ears in which an initial study had shown a middle ear pressure of less than or equal to -100 mm H2O. At the repeated test 20% had pathological pure tone screening, 40% had a middle ear pressure of less than or equal to -100 mm H2O, 57% had elevated or nonelicitable stapedius reflexes, and 14% had middle ear effusion. The high frequency of persisting abnormal middle ear pressure and effusion in these 357 ears suggests that a middle ear pressure of less than or equal to -100 mm H2O can be a predisposing factor for SOM. In an experimental study on human temporal bones it was demonstrated that the tympanogram preserves its original appearance when the water level is low in the middle ear, while a higher level gives rise to a pathological tympanogram. It is also demonstrated that there is a discrepancy between the tympanometrically, indirectly recorded middle ear pressure and the middle ear pressure as measured manometrically, directly from the middle ear."} {"id": "PMID:1267354", "title": "Anatomy of the normal and cleft palate Eustachian tube.", "content": "This report presents preliminary findings from a study of cleft palate and noncleft palate human fetuses to determine whether differences in Eustachian tube and cranial base structures could be found which might explain the universal appearance of otitis media in infants with cleft palate. Differences were found which are consistent with the previous hypothesis of reduced elasticity in the Eustachian tube. Principal findings included medial to lateral compression of the tube and reduced tubal width.", "contents": "Anatomy of the normal and cleft palate Eustachian tube. This report presents preliminary findings from a study of cleft palate and noncleft palate human fetuses to determine whether differences in Eustachian tube and cranial base structures could be found which might explain the universal appearance of otitis media in infants with cleft palate. Differences were found which are consistent with the previous hypothesis of reduced elasticity in the Eustachian tube. Principal findings included medial to lateral compression of the tube and reduced tubal width."} {"id": "PMID:1267356", "title": "Myringostomy for middle ear effusions. Results of a two-year study.", "content": "From 1972 to 1974, 736 children had tympanostomy tubes inserted for chronic serous otitis media resistant to medical therapy. The total number of ears involved was 2,237. The cleft palate patients constituted 8.8% of the total and had 15.4% of all procedures. Patients with allergy comprised 19% of the total population and had a higher incidence of otitis media following tube insertion. Adenoidectomy was performed in 44% of all patients and 35% of these required further tube insertions, suggesting that adenoidectomy in combination with tube insertion is not necessarily the primary treatment of choice. Children under six made up 78.5% of the total. The most common complication, a draining ear with an incidence of 15.1% was treated successfully with aqueous Merthiolate irrigations. There were 14 tympanic membrane perforations.", "contents": "Myringostomy for middle ear effusions. Results of a two-year study. From 1972 to 1974, 736 children had tympanostomy tubes inserted for chronic serous otitis media resistant to medical therapy. The total number of ears involved was 2,237. The cleft palate patients constituted 8.8% of the total and had 15.4% of all procedures. Patients with allergy comprised 19% of the total population and had a higher incidence of otitis media following tube insertion. Adenoidectomy was performed in 44% of all patients and 35% of these required further tube insertions, suggesting that adenoidectomy in combination with tube insertion is not necessarily the primary treatment of choice. Children under six made up 78.5% of the total. The most common complication, a draining ear with an incidence of 15.1% was treated successfully with aqueous Merthiolate irrigations. There were 14 tympanic membrane perforations."} {"id": "PMID:1267357", "title": "Comparative study of various ventilating tubes.", "content": "In less than 20 years, insertion of middle ear ventilating tubes has become perhaps the most common operative procedure. It was not possible to find a study that adequately compares the performance of the many different types of tympanostomy tubes available. The ideal ventilating tube is defined; it has not yet been designed.", "contents": "Comparative study of various ventilating tubes. In less than 20 years, insertion of middle ear ventilating tubes has become perhaps the most common operative procedure. It was not possible to find a study that adequately compares the performance of the many different types of tympanostomy tubes available. The ideal ventilating tube is defined; it has not yet been designed."} {"id": "PMID:1267355", "title": "Antibacterial therapy and middle ear effusions.", "content": "Antimicrobial drugs chosen for their activity against the causative pathogens of otitis media provide effective treatment for acute attacks. Prolonged administration of some of these agents has recently been shown to be of value in the prevention of symptomatic otitis. The role of drug therapy in the management of chronic or recurrent middle ear effusion is unknown at present.", "contents": "Antibacterial therapy and middle ear effusions. Antimicrobial drugs chosen for their activity against the causative pathogens of otitis media provide effective treatment for acute attacks. Prolonged administration of some of these agents has recently been shown to be of value in the prevention of symptomatic otitis. The role of drug therapy in the management of chronic or recurrent middle ear effusion is unknown at present."} {"id": "PMID:1267359", "title": "Clinical results and complications of tympanostomy.", "content": "Tympanostomy tube treatment was used in 181 patients on 323 ears and a followup study was made as an average three years and two months later. Sixty-five percent of the ears had healed completely and in these the average tube treatment time had been 11.3 months. In 22% the tubes were still in position, the average time for treatment being 24.2 months. Five percent showed purulent discharge and recurrence of the glue ear was noted in 3%. A dry perforation developed in five patients. Cholesteatoma was seen in four ears but in only one of these it may have been related to the location of the tube at the posterior drum margin.", "contents": "Clinical results and complications of tympanostomy. Tympanostomy tube treatment was used in 181 patients on 323 ears and a followup study was made as an average three years and two months later. Sixty-five percent of the ears had healed completely and in these the average tube treatment time had been 11.3 months. In 22% the tubes were still in position, the average time for treatment being 24.2 months. Five percent showed purulent discharge and recurrence of the glue ear was noted in 3%. A dry perforation developed in five patients. Cholesteatoma was seen in four ears but in only one of these it may have been related to the location of the tube at the posterior drum margin."} {"id": "PMID:1267360", "title": "Adenoidectomy in relation to otitis media.", "content": "Past studies of the efficacy of adenoidectomy in the management of children with otitis media have been inconclusive due to significant limitations in experimental design. At the Children's Hospital of Pittsburgh, the effect of adenoidectomy on the outcome of otitis media is currently being studied in a prospective manner. An attempt is being made to document and to control those factors cited as lacking in the previous studies. This report describes the techniques for assessment of nasal and Eustachian tube function and for the completeness of adenoidectomy.", "contents": "Adenoidectomy in relation to otitis media. Past studies of the efficacy of adenoidectomy in the management of children with otitis media have been inconclusive due to significant limitations in experimental design. At the Children's Hospital of Pittsburgh, the effect of adenoidectomy on the outcome of otitis media is currently being studied in a prospective manner. An attempt is being made to document and to control those factors cited as lacking in the previous studies. This report describes the techniques for assessment of nasal and Eustachian tube function and for the completeness of adenoidectomy."} {"id": "PMID:1267358", "title": "Membrane ventilating tube for the middle ear.", "content": "A pilot study was conducted to evaluate the efficacy of a membrane ventilating tube as a Eustachian tube prosthesis in 20 patients with otitis media. The design was based partly on assumptions since many of the physiological parameters required to calculate the gas transport processes have not been previously reported. An elementary gas transport model with assumed partial pressures of gases was developed. A semipermeable membrane covering a tympanostomy tube was fashioned and used to ventilate the middle ear cavity. From this preliminary investigation, the device successfully maintained atmospheric pressures in the tympanum, compensated for Eustachian tube malfunction, prevented otorrhea and recurrence of middle ear effusions.", "contents": "Membrane ventilating tube for the middle ear. A pilot study was conducted to evaluate the efficacy of a membrane ventilating tube as a Eustachian tube prosthesis in 20 patients with otitis media. The design was based partly on assumptions since many of the physiological parameters required to calculate the gas transport processes have not been previously reported. An elementary gas transport model with assumed partial pressures of gases was developed. A semipermeable membrane covering a tympanostomy tube was fashioned and used to ventilate the middle ear cavity. From this preliminary investigation, the device successfully maintained atmospheric pressures in the tympanum, compensated for Eustachian tube malfunction, prevented otorrhea and recurrence of middle ear effusions."} {"id": "PMID:1267361", "title": "Management of middle ear effusions in infants with cleft palate.", "content": "Middle ear effusion is now generally recognized as a virtually universal complication in infants with cleft palate. Such infants may therefore be assumed to experience conductive hearing loss of some degree or other throughout infancy. Hoping to prevent not only deficits in intellectual and language development, but also permanent otic and auditory handicaps, we have routinely treated such infants as early as practicable with myringotomy and tympanostomy tube insertion. Subsequently, we have repeated the operation whenever blockage or extrusion of the tubes resulted in recurrence of persistent effusion. In this manner we have been able to maintain most infants in satisfactory middle ear status most of the time. Otorrhea, however, has been a frequent complication. Preliminary findings suggest that infants managed according to this regimen may eventually develop better language function than those not receiving such management. A current study is designed to test the advantages and disadvantages that might result from deferring the initial routine myringotomy until somewhate later in infancy.", "contents": "Management of middle ear effusions in infants with cleft palate. Middle ear effusion is now generally recognized as a virtually universal complication in infants with cleft palate. Such infants may therefore be assumed to experience conductive hearing loss of some degree or other throughout infancy. Hoping to prevent not only deficits in intellectual and language development, but also permanent otic and auditory handicaps, we have routinely treated such infants as early as practicable with myringotomy and tympanostomy tube insertion. Subsequently, we have repeated the operation whenever blockage or extrusion of the tubes resulted in recurrence of persistent effusion. In this manner we have been able to maintain most infants in satisfactory middle ear status most of the time. Otorrhea, however, has been a frequent complication. Preliminary findings suggest that infants managed according to this regimen may eventually develop better language function than those not receiving such management. A current study is designed to test the advantages and disadvantages that might result from deferring the initial routine myringotomy until somewhate later in infancy."} {"id": "PMID:1267362", "title": "Mastoidectomy and epitympanotomy.", "content": "The procedure of mastoidectomy and epitympanotomy effected a two-year arrest of serous otitis media and correction of a refractory retraction pocket in 12 out of 20 patients with one patient lost to follow-up. Each mastoid and epitympanum was extensively involved with chronically inflamed tissue which surrounded the ossicles and chorda tympani nerve.", "contents": "Mastoidectomy and epitympanotomy. The procedure of mastoidectomy and epitympanotomy effected a two-year arrest of serous otitis media and correction of a refractory retraction pocket in 12 out of 20 patients with one patient lost to follow-up. Each mastoid and epitympanum was extensively involved with chronically inflamed tissue which surrounded the ossicles and chorda tympani nerve."} {"id": "PMID:1267363", "title": "Blue ear drum and its management.", "content": "The \"blue ear drum\" generally refers to a condition in which blood or blood products are found in the middle ear. After all possible causes for hemotympanum, including blood dyscrasias and trauma are searched for and ruled out, the patient may have chronic serous otitis media accompanied by bloody effusion. Treatment for all of these patients is conservative, consisting of medical therapy and, if need be, myringotomy and insertion of ventilation tubes. In spite of proper treatment, rarely the condition may progress, over a long period of time, to a state of intractability. Characteristic findings are a hypocellular mastoid, hyperplastic and metaplastic mucoperiosteal lining, including the presence of glands and cysts and cholesterin granuloma. The recommended procedure is a modified radical mastoidectomy, placement of silicone rubber sheeting in the middle ear and insertion of a ventilation tube. It is to be emphasized that mastoid surgery is rarely indicated for these patients and only after all else has failed.", "contents": "Blue ear drum and its management. The \"blue ear drum\" generally refers to a condition in which blood or blood products are found in the middle ear. After all possible causes for hemotympanum, including blood dyscrasias and trauma are searched for and ruled out, the patient may have chronic serous otitis media accompanied by bloody effusion. Treatment for all of these patients is conservative, consisting of medical therapy and, if need be, myringotomy and insertion of ventilation tubes. In spite of proper treatment, rarely the condition may progress, over a long period of time, to a state of intractability. Characteristic findings are a hypocellular mastoid, hyperplastic and metaplastic mucoperiosteal lining, including the presence of glands and cysts and cholesterin granuloma. The recommended procedure is a modified radical mastoidectomy, placement of silicone rubber sheeting in the middle ear and insertion of a ventilation tube. It is to be emphasized that mastoid surgery is rarely indicated for these patients and only after all else has failed."} {"id": "PMID:1267365", "title": "Ultrastructure of the middle ear mucosa.", "content": "Histologic studies of recent years have definitely concluded that the epithelium of the middle ear is a modified respiratory epithelium with ciliated and secretory cells, including goblet cells. These cells, like the ciliated cells, are developd from the basal cell and are just ordinary secretory cells completely filled with secretory granules. For different reasons it is postulated, that the dark secretory granules are prestages of the actual secretory product presenting as light granules and that dark and light granules do not represent different secretory capacities of the cell. The subepithelial layer which consists of loose connective tissue is a structure of just as great importance as the epithelial layer.", "contents": "Ultrastructure of the middle ear mucosa. Histologic studies of recent years have definitely concluded that the epithelium of the middle ear is a modified respiratory epithelium with ciliated and secretory cells, including goblet cells. These cells, like the ciliated cells, are developd from the basal cell and are just ordinary secretory cells completely filled with secretory granules. For different reasons it is postulated, that the dark secretory granules are prestages of the actual secretory product presenting as light granules and that dark and light granules do not represent different secretory capacities of the cell. The subepithelial layer which consists of loose connective tissue is a structure of just as great importance as the epithelial layer."} {"id": "PMID:1267366", "title": "Functional morphology of the mucosa of the middle ear and Eustachian tube.", "content": "A review of available histological, histochemical and ultrastructural data on middle ear mucosa and the Eustachian tube was made to provide a broad cellular basis for understanding middle ear effusions. The presence of mucociliary defense system in a large part of the Eustachian tube and middle ear is seen as the first line of defense. Secretion by the mucosa has a profound biological significance. Immunoglobulins A, G, and even E and M are produced locally by the mucosa and may contribute to the immunodefense of the middle ear. Secretory lysozyme is also produced by the mucosa and may contribute enzymatic defense of the ear. Mucosal immunoglobulins and lysozyme are significantly elevated in the effusions, which would imply that local defense systems are hyperactive in OME. It also appears that these increases are related to the increase of the secretory cell population. It is also suspected that auditory surface-active agent is produced locally and may facilitate normal function of the tube. The middle ear also can transport macromolecules very rapidly across intact mucosal epithelium. The large numbers of tissue and wandering macrophages found in the mucosa and effusions would also imply that the middle ear is capable of efficient phagocytosis, which may be involved in processing antigen.", "contents": "Functional morphology of the mucosa of the middle ear and Eustachian tube. A review of available histological, histochemical and ultrastructural data on middle ear mucosa and the Eustachian tube was made to provide a broad cellular basis for understanding middle ear effusions. The presence of mucociliary defense system in a large part of the Eustachian tube and middle ear is seen as the first line of defense. Secretion by the mucosa has a profound biological significance. Immunoglobulins A, G, and even E and M are produced locally by the mucosa and may contribute to the immunodefense of the middle ear. Secretory lysozyme is also produced by the mucosa and may contribute enzymatic defense of the ear. Mucosal immunoglobulins and lysozyme are significantly elevated in the effusions, which would imply that local defense systems are hyperactive in OME. It also appears that these increases are related to the increase of the secretory cell population. It is also suspected that auditory surface-active agent is produced locally and may facilitate normal function of the tube. The middle ear also can transport macromolecules very rapidly across intact mucosal epithelium. The large numbers of tissue and wandering macrophages found in the mucosa and effusions would also imply that the middle ear is capable of efficient phagocytosis, which may be involved in processing antigen."} {"id": "PMID:1267367", "title": "Goblet cell population in the normal middle ear and Eustachian tube of children and adults.", "content": "On 54 temporal bones from entirely normal prematures and newborn infants, children, and adults, 30,000 to 90,000 counts of goblet cells were done in different parts of the Eustachian tube and middle ear. In the Eustachian tube, normal prematures showed a very low density of goblet cells in all localities, increasing in the pharyngeal parts gradually through childhood and reaching in the normal adult a very high density in the pharyngeal orifice. There are no differences in density between the medial and lateral wall, but in some parts a decrease of density towards the tubal roof. In the middle ear the density is low in normal prematures, increasing slightly in infants, and decreasing again during the age range 7-14 years and in adults. Goblet cells are present in all middle-ear localities, but in markedly decreasing density in this sequence: hypotympanum anteriorly, posteriorly, promontory anteriorly, in the middle, epitympanum, niche of oval window, antrum, niche of round window, mastoid process, incus, and promontory posteriorly.", "contents": "Goblet cell population in the normal middle ear and Eustachian tube of children and adults. On 54 temporal bones from entirely normal prematures and newborn infants, children, and adults, 30,000 to 90,000 counts of goblet cells were done in different parts of the Eustachian tube and middle ear. In the Eustachian tube, normal prematures showed a very low density of goblet cells in all localities, increasing in the pharyngeal parts gradually through childhood and reaching in the normal adult a very high density in the pharyngeal orifice. There are no differences in density between the medial and lateral wall, but in some parts a decrease of density towards the tubal roof. In the middle ear the density is low in normal prematures, increasing slightly in infants, and decreasing again during the age range 7-14 years and in adults. Goblet cells are present in all middle-ear localities, but in markedly decreasing density in this sequence: hypotympanum anteriorly, posteriorly, promontory anteriorly, in the middle, epitympanum, niche of oval window, antrum, niche of round window, mastoid process, incus, and promontory posteriorly."} {"id": "PMID:1267368", "title": "Autonomic nervous system of the cat middle ear mucosa.", "content": "The autonomic nerves of the cat middle ear mucosa were studied by the methods of surface preparation, histochemistry and electron microscopy. The tympanic nerve was found to contain large myelinated fibers probably of a sensory nature. Other sympathetic bundles consisted primarily of unmyelinated fibers with a sparse distribution of myelinated fibers. The inferior tympanic artery was accompanied by many vasomotor nerves and its branches were also innervated predominantly by adrenergic fibers. A dense neural network which showed acetylcholinesterase activity was found in the mucosa around the Eustachian tube orifice. These nerves consisted of several unmyelinated fibers encapsulated by a single Schwann cell just below the epithelium. The fine structure of the small ganglions of the tympanic plexus revealed that the cholinergic nerve endings synapse with the cell body of the ganglion. This finding suggests that these ganglions are autonomic.", "contents": "Autonomic nervous system of the cat middle ear mucosa. The autonomic nerves of the cat middle ear mucosa were studied by the methods of surface preparation, histochemistry and electron microscopy. The tympanic nerve was found to contain large myelinated fibers probably of a sensory nature. Other sympathetic bundles consisted primarily of unmyelinated fibers with a sparse distribution of myelinated fibers. The inferior tympanic artery was accompanied by many vasomotor nerves and its branches were also innervated predominantly by adrenergic fibers. A dense neural network which showed acetylcholinesterase activity was found in the mucosa around the Eustachian tube orifice. These nerves consisted of several unmyelinated fibers encapsulated by a single Schwann cell just below the epithelium. The fine structure of the small ganglions of the tympanic plexus revealed that the cholinergic nerve endings synapse with the cell body of the ganglion. This finding suggests that these ganglions are autonomic."} {"id": "PMID:1267369", "title": "Clearance of middle ear effusions and middle ear pressures.", "content": "Twenty-six children presenting bilateral secretory otitis media (SOM) had ventilating tubes inserted into both middle ears. Mucus was, however, aspirated only from one ear, the right side. The vast majority of ears right and left were seen to have cleared their effusion equally well regardless of whether they were aspirated on not. This experiment points toward the essential intactness of the mucociliary system and the patency of the lumen of the Eustachian tube in SOM. Promotion of middle ear clearance through ventilation, which reminds one of the second opening in a beer can, does obviously suggest the relief of some negative pressure. Direct manometric measurements of SOM middle pressure were performed in 41 ears showing negative pressure averaging --1.7 mm H2O, this range being two orders of magnitude less than tympanometric measurements. Normal ears did not have even such a small negative pressure. The validity of these direct manometric measurements was checked against a model of the middle ear. Tympanometry, which is a valid diagnostic tool, does indicate in all probability the presence of middle ear effusion due to its rheologic effects on the drum and ossicles rather than the measure of actual middle ear pressures. This is determined by the fact that direct needling of the middle ear, or even the insertion of a ventilating tube, did not change tympanometric values but aspiration of part of the effusion did: indeed the latter tended to bring manometry to normal values.", "contents": "Clearance of middle ear effusions and middle ear pressures. Twenty-six children presenting bilateral secretory otitis media (SOM) had ventilating tubes inserted into both middle ears. Mucus was, however, aspirated only from one ear, the right side. The vast majority of ears right and left were seen to have cleared their effusion equally well regardless of whether they were aspirated on not. This experiment points toward the essential intactness of the mucociliary system and the patency of the lumen of the Eustachian tube in SOM. Promotion of middle ear clearance through ventilation, which reminds one of the second opening in a beer can, does obviously suggest the relief of some negative pressure. Direct manometric measurements of SOM middle pressure were performed in 41 ears showing negative pressure averaging --1.7 mm H2O, this range being two orders of magnitude less than tympanometric measurements. Normal ears did not have even such a small negative pressure. The validity of these direct manometric measurements was checked against a model of the middle ear. Tympanometry, which is a valid diagnostic tool, does indicate in all probability the presence of middle ear effusion due to its rheologic effects on the drum and ossicles rather than the measure of actual middle ear pressures. This is determined by the fact that direct needling of the middle ear, or even the insertion of a ventilating tube, did not change tympanometric values but aspiration of part of the effusion did: indeed the latter tended to bring manometry to normal values."} {"id": "PMID:1267370", "title": "Atelectasis and secretory otitis media.", "content": "That condition where the tympanic membrane is displaced toward the promontory is termed atelectasis. Thirty-seven patients (61 ears) showing various degrees of atelectasis graded from stage 1 to stage 4 were studied. Atelectatic drums are an inflammatory phenomenon occurring in underventilated ears. This conclusion is reached by considering the reversibility of the atelectasis upon ventilation; while the inflammatory factor can be deduced from the history and histopathology of the atelectatic drum, as well as the histology of the necrosed incus, the latter occurs in over a third of our cases. Also pneumatization of the mastoid is almost never present. Twelve (21%) of the ears treated did indeed develop a perforation at one time or another (two had cholesteatomas). Chronic granulating external otitis with specific features occurred in 15% of cases. The characteristics of these ears and their case histories lead us to view atelectatic ears as part of the otitis media syndrome, where their place is somehow transitional between secretory otitis media on the one hand and chronic otitis media on the other.", "contents": "Atelectasis and secretory otitis media. That condition where the tympanic membrane is displaced toward the promontory is termed atelectasis. Thirty-seven patients (61 ears) showing various degrees of atelectasis graded from stage 1 to stage 4 were studied. Atelectatic drums are an inflammatory phenomenon occurring in underventilated ears. This conclusion is reached by considering the reversibility of the atelectasis upon ventilation; while the inflammatory factor can be deduced from the history and histopathology of the atelectatic drum, as well as the histology of the necrosed incus, the latter occurs in over a third of our cases. Also pneumatization of the mastoid is almost never present. Twelve (21%) of the ears treated did indeed develop a perforation at one time or another (two had cholesteatomas). Chronic granulating external otitis with specific features occurred in 15% of cases. The characteristics of these ears and their case histories lead us to view atelectatic ears as part of the otitis media syndrome, where their place is somehow transitional between secretory otitis media on the one hand and chronic otitis media on the other."} {"id": "PMID:1267371", "title": "Role of perilymph in the early stage of serous otitis.", "content": "After injection of an electron-dense tracer into the cerebrospinal fluid (CSF) the particles can be seen within the lymphatic spaces of the middle ear mucosa after a few minutes. They find their way via the well known communication routes from CSF to the perilymphatic spaces of the inner ear. From there they enter through open fluid spaces into the fibrocytic network of the round window membrane which stands in open relationship to the extracellular fluid spaces of the middle ear mucosa. They were drained to the regional lymph nodes by lymphatic vessels. When inducing a serous otitis by experimental obstruction of the Eustachian tube it could be demonstrated that the fluid within the middle ear cavity is partly coming from the CSF and perilymph. Later the healing process of the middle ear epithelium was studied after the onset of serous otitis with and without artificial ventilation of the middle ear.", "contents": "Role of perilymph in the early stage of serous otitis. After injection of an electron-dense tracer into the cerebrospinal fluid (CSF) the particles can be seen within the lymphatic spaces of the middle ear mucosa after a few minutes. They find their way via the well known communication routes from CSF to the perilymphatic spaces of the inner ear. From there they enter through open fluid spaces into the fibrocytic network of the round window membrane which stands in open relationship to the extracellular fluid spaces of the middle ear mucosa. They were drained to the regional lymph nodes by lymphatic vessels. When inducing a serous otitis by experimental obstruction of the Eustachian tube it could be demonstrated that the fluid within the middle ear cavity is partly coming from the CSF and perilymph. Later the healing process of the middle ear epithelium was studied after the onset of serous otitis with and without artificial ventilation of the middle ear."} {"id": "PMID:1267372", "title": "Middle ear effusions: definitions and terminology.", "content": "There are many confusing terms which presently apply to the group of clinical problems accompanied by middle ear effusion manifestations. Out of this chaos there is a need for logic and simplicity. All of the middle ear effusions are examples of the broadly descriptive categorical term \"otitis media\" meaning \"inflammation\" of the middle ear which includes examples of frank \"infection\" as well. Based upon clinical and laboratory observations there are essentially four types of intrinsically occurring middle ear fluid which, along with clinical findings, provide the means of identifying the clinically descriptive term which should be used: 1) serous fluid (serous otitis media); 2) mucoid fluid (mucoid otitis media, secretory otitis media, glue ear); 3) bloody fluid (barotrauma, aerotitis); 4) purulent fluid (purulent or suppurative otitis media); and 5) any combination of the above four (e.g., seropurulent otitis media, serosanguineous otitis media, mucopurulent otitis media, etc.).", "contents": "Middle ear effusions: definitions and terminology. There are many confusing terms which presently apply to the group of clinical problems accompanied by middle ear effusion manifestations. Out of this chaos there is a need for logic and simplicity. All of the middle ear effusions are examples of the broadly descriptive categorical term \"otitis media\" meaning \"inflammation\" of the middle ear which includes examples of frank \"infection\" as well. Based upon clinical and laboratory observations there are essentially four types of intrinsically occurring middle ear fluid which, along with clinical findings, provide the means of identifying the clinically descriptive term which should be used: 1) serous fluid (serous otitis media); 2) mucoid fluid (mucoid otitis media, secretory otitis media, glue ear); 3) bloody fluid (barotrauma, aerotitis); 4) purulent fluid (purulent or suppurative otitis media); and 5) any combination of the above four (e.g., seropurulent otitis media, serosanguineous otitis media, mucopurulent otitis media, etc.)."} {"id": "PMID:1267377", "title": "Mortality and morbidity following road accidents.", "content": "The results of a prospective study of the victims of road traffic accidents from the time of injury until their discharge from hospital or death are reported. Data on 2392 surviving hospital admissions and 344 deaths were collected over a period of one year from 12 hospitals covering a wide area in northern England.", "contents": "Mortality and morbidity following road accidents. The results of a prospective study of the victims of road traffic accidents from the time of injury until their discharge from hospital or death are reported. Data on 2392 surviving hospital admissions and 344 deaths were collected over a period of one year from 12 hospitals covering a wide area in northern England."} {"id": "PMID:1267378", "title": "The incidence and clinical significance of rectal polyps.", "content": "Adenomata of the large bowel were discovered at proctosigmoidoscopy in 28 out of 1000 patients examined; this is a much lower frequency than those reported from American sources. The distribution and histological features of these tumours are considered and lack of correlation between the microscopic and macroscopic characters noted.", "contents": "The incidence and clinical significance of rectal polyps. Adenomata of the large bowel were discovered at proctosigmoidoscopy in 28 out of 1000 patients examined; this is a much lower frequency than those reported from American sources. The distribution and histological features of these tumours are considered and lack of correlation between the microscopic and macroscopic characters noted."} {"id": "PMID:1267373", "title": "Middle ear effusion in experimental hypersensitivity.", "content": "Monkeys which were transfused with human serum containing a specific antibody developed a clear, middle ear effusion when the appropriate antigen (ragweed) was insufflated into their middle ear space via the Eustachian tube. The typical histological changes expected to occur in an immediate type 1 immune response were present. Intracellular edema, capillary dilation, and an initial exudative reaction were all seen. Serum IgE levels were found to be significantly raised in the animal following passive sensitization. IgE was also present in the effusion, and IgE specific fluorescent mast and plasma cells were noted in the middle ear mucosa of the sensitized animals.", "contents": "Middle ear effusion in experimental hypersensitivity. Monkeys which were transfused with human serum containing a specific antibody developed a clear, middle ear effusion when the appropriate antigen (ragweed) was insufflated into their middle ear space via the Eustachian tube. The typical histological changes expected to occur in an immediate type 1 immune response were present. Intracellular edema, capillary dilation, and an initial exudative reaction were all seen. Serum IgE levels were found to be significantly raised in the animal following passive sensitization. IgE was also present in the effusion, and IgE specific fluorescent mast and plasma cells were noted in the middle ear mucosa of the sensitized animals."} {"id": "PMID:1267375", "title": "Secretory IgA and antibody activities in middle ear effusions.", "content": "Secretory IgA (SIgA) was isolated from pooled middle ear effusions (MEE) and its antigenicity and subunit structure were found to be identical to those of SIgA in saliva, nasal secretion and colostrum. The calculated percentage of SIgA in the total IgA of effusions was approximately 11%. Although the SIgA antibodies against streptolysin and staphylolysin were very low when compared to that of IgG class in effusion, this finding confirmed that MEE is at least partially a result of local immunologic reactions. The IgE concentration did not become elevated in both the MEE and serum obtained from patients with otitis media with effusion. Specific reaginic activity against mites was found in 5 of 56 (8.9%) MEE. Our findings would not suggest the significant role of atopic allergy in the formation of MEE.", "contents": "Secretory IgA and antibody activities in middle ear effusions. Secretory IgA (SIgA) was isolated from pooled middle ear effusions (MEE) and its antigenicity and subunit structure were found to be identical to those of SIgA in saliva, nasal secretion and colostrum. The calculated percentage of SIgA in the total IgA of effusions was approximately 11%. Although the SIgA antibodies against streptolysin and staphylolysin were very low when compared to that of IgG class in effusion, this finding confirmed that MEE is at least partially a result of local immunologic reactions. The IgE concentration did not become elevated in both the MEE and serum obtained from patients with otitis media with effusion. Specific reaginic activity against mites was found in 5 of 56 (8.9%) MEE. Our findings would not suggest the significant role of atopic allergy in the formation of MEE."} {"id": "PMID:1267403", "title": "Diagnostic aspects in 117 patients treated surgically for thyroid carcinoma.", "content": "A series of 117 patients operated on for thyroid carcinoma from 1969-1973 is compared with a previous series of 115 cases treated from 1956-1968, with the object of clarifying diagnostic aspects and indications for primary operation. In the group with papillary carcinomas there was a high peak of incidence among young patients both females and males aged 20 to 30 years. In the present series the incidence of metastases was less than in the previous series. Lymph node metastases in the neck were the only metastases in papillary and medullary carcinomas. The time interval between beginning of treatment and appearance of main symptoms had decreased noticeably. The pre- and peroperative diagnostic procedures employed made it possible to operate as the primary procedure in 78% of papillary, 100% medullary and 86% anaplastic tumours, but only in 52% of follicular carcinomas. The most common reason for diagnostic failure was that frozen section had not been performed during the primary operation. The value of both aspiration biopsy and frozen section was dependent on the histological type of the tumour; it was more reliable in papillary and anaplastic than in follicular carcinomas. The operability rate had not changed essentially, 94% of papillary and 85% of follicular, but only 24% of anaplastic primary tumours could be radically removed. The value of establishing a firm diagnosis is to be able to operate as a primary procedure in these tumours when less operative complications occur.", "contents": "Diagnostic aspects in 117 patients treated surgically for thyroid carcinoma. A series of 117 patients operated on for thyroid carcinoma from 1969-1973 is compared with a previous series of 115 cases treated from 1956-1968, with the object of clarifying diagnostic aspects and indications for primary operation. In the group with papillary carcinomas there was a high peak of incidence among young patients both females and males aged 20 to 30 years. In the present series the incidence of metastases was less than in the previous series. Lymph node metastases in the neck were the only metastases in papillary and medullary carcinomas. The time interval between beginning of treatment and appearance of main symptoms had decreased noticeably. The pre- and peroperative diagnostic procedures employed made it possible to operate as the primary procedure in 78% of papillary, 100% medullary and 86% anaplastic tumours, but only in 52% of follicular carcinomas. The most common reason for diagnostic failure was that frozen section had not been performed during the primary operation. The value of both aspiration biopsy and frozen section was dependent on the histological type of the tumour; it was more reliable in papillary and anaplastic than in follicular carcinomas. The operability rate had not changed essentially, 94% of papillary and 85% of follicular, but only 24% of anaplastic primary tumours could be radically removed. The value of establishing a firm diagnosis is to be able to operate as a primary procedure in these tumours when less operative complications occur."} {"id": "PMID:1267404", "title": "Peritoneal lavage with doxycycline in acute diffuse peritonitis.", "content": "Peritoneal lavage with ten hourly repeated instillation-drainages of one litre lavage fluid containing 50 mg doxycycline (Vibramycin Pfizer) was carried out on six patients suffering from diffuse peritonitis due to perforated appendicitis. Bacteriological specimens were obtained both from the perforation in the appendix and the peritoneal fluid at operation and the doxycycline concentrations in blood and lavage fluid were determined at intervals up to 72 hours postoperatively. All the patients recovered, but the lavage was considered a failure in one case as a small abscess and multiple adhesions were found at reoperation 1 1/2 months later. Bacteriological swabs from the perforated appendix and the peritoneal fluid usually contained the same bacteriological species, and as a rule several species were isolated. Doxycycline compared favourably with ampicillin as regards bacterial sensitivity, but the difference was too slight to be of practical importance. Doxycycline was absorbed very rapidly from the peritoneal cavitiy, and due to its slow excretion a cumulation occurred. In this small series doxycycline did not appear to give any real advantage over ampicillin, but it may be considered the drug of choice in patients with penicillin allergy, and in those who fail to respond to ampicillin.", "contents": "Peritoneal lavage with doxycycline in acute diffuse peritonitis. Peritoneal lavage with ten hourly repeated instillation-drainages of one litre lavage fluid containing 50 mg doxycycline (Vibramycin Pfizer) was carried out on six patients suffering from diffuse peritonitis due to perforated appendicitis. Bacteriological specimens were obtained both from the perforation in the appendix and the peritoneal fluid at operation and the doxycycline concentrations in blood and lavage fluid were determined at intervals up to 72 hours postoperatively. All the patients recovered, but the lavage was considered a failure in one case as a small abscess and multiple adhesions were found at reoperation 1 1/2 months later. Bacteriological swabs from the perforated appendix and the peritoneal fluid usually contained the same bacteriological species, and as a rule several species were isolated. Doxycycline compared favourably with ampicillin as regards bacterial sensitivity, but the difference was too slight to be of practical importance. Doxycycline was absorbed very rapidly from the peritoneal cavitiy, and due to its slow excretion a cumulation occurred. In this small series doxycycline did not appear to give any real advantage over ampicillin, but it may be considered the drug of choice in patients with penicillin allergy, and in those who fail to respond to ampicillin."} {"id": "PMID:1267405", "title": "Results of regional portal infusion of 5-fluorouracil in patients with primary and secondary liver cancer.", "content": "The survival of 47 patients with liver malignancies treated with continuous portal infusion of fluorouracil (5-FU) has been studied. 18 of them had been treated initially by hepatic artery ligation. Total mean survival was 9.4 months. Patients treated with hepatic artery ligation + 5-FU lived longer (mean 10.8 months) than those treated with 5-FU alone (7.4 months). The survival was longer than could be expected for patients treated for primary liver cancer or for liver metastases from colo-rectal cancer, when compared with the \"untreated\" group. It is concluded that continuous portal infusion of 5-FU appears to prolong survival in some groups of patients with malignant liver tumours. However, the influence of \"unspecific, general\" therapy is difficult to evaluate.", "contents": "Results of regional portal infusion of 5-fluorouracil in patients with primary and secondary liver cancer. The survival of 47 patients with liver malignancies treated with continuous portal infusion of fluorouracil (5-FU) has been studied. 18 of them had been treated initially by hepatic artery ligation. Total mean survival was 9.4 months. Patients treated with hepatic artery ligation + 5-FU lived longer (mean 10.8 months) than those treated with 5-FU alone (7.4 months). The survival was longer than could be expected for patients treated for primary liver cancer or for liver metastases from colo-rectal cancer, when compared with the \"untreated\" group. It is concluded that continuous portal infusion of 5-FU appears to prolong survival in some groups of patients with malignant liver tumours. However, the influence of \"unspecific, general\" therapy is difficult to evaluate."} {"id": "PMID:1267406", "title": "Retroperitoneal injuries of the duodenum caused by blunt abdominal trauma.", "content": "Five patients with blunt retroperitoneal injury of the duodenum are presented. In three of them the trauma was caused by a traffic accident, the most common mechanism of such injuries. One patient died. The high index of suspicion is still the best indication for laparotomy in retroperitoneal injuries of the duodenum, because no typical finding or reliably diagnostic test could be demonstrated even in the present study. The proper treatment in less severe injuries of the retroperitoneal duodenum is evacuation of the hematoma or simple suture of the rupture with drainage and naso-gastric suction. Internal drainage as an afferent jejunostomy is sometimes necessary in the treatment of more severe injuries. Pancreatoduodenectomy is to be reserved for only the very severe duodenal injuries, where the head of the pancreas is badly crushed.", "contents": "Retroperitoneal injuries of the duodenum caused by blunt abdominal trauma. Five patients with blunt retroperitoneal injury of the duodenum are presented. In three of them the trauma was caused by a traffic accident, the most common mechanism of such injuries. One patient died. The high index of suspicion is still the best indication for laparotomy in retroperitoneal injuries of the duodenum, because no typical finding or reliably diagnostic test could be demonstrated even in the present study. The proper treatment in less severe injuries of the retroperitoneal duodenum is evacuation of the hematoma or simple suture of the rupture with drainage and naso-gastric suction. Internal drainage as an afferent jejunostomy is sometimes necessary in the treatment of more severe injuries. Pancreatoduodenectomy is to be reserved for only the very severe duodenal injuries, where the head of the pancreas is badly crushed."} {"id": "PMID:1267407", "title": "Intestinal blind pouch- and blind loop-syndrome in children operated previously for congenital duodenal obstruction.", "content": "A follow-up study of 27 children operated for congenital duodenal obstruction (CDO) in years 1953-71 is presented. Nine children belonged to the intrinsic and 18 children to the extrinsic group of CDO. A total of 7 retrocolic, isoperistaltic, side-to-side duodeno-jejunostomy, 7 Ladd's operation, 8 duodenolysis, 2 reduction of midgut volvulus, 2 duodenostomy a.m. Morton and one gastro-jejunostomy were performed at the age of 1 day-15 years. The clinical and radiological examinations were performed 3-21 years (mean 10 years 2 months) after these operations. In 3 cases there was a moderate duodenal dilation, but reoperation was not necessary. During the follow-up period, one boy, now aged 8 years, developed a blind pouch-syndrome in the I portion of the duodenum containing a 5 X 5 cm phytobezoar 4 1/2 years after duodeno-jejunostomy. The frequency of blind pouch-syndrome after duodeno-jejunostomy was thus 1:7 or 14%. One girl, now aged 9 years, developed a blind loop-syndrome in the ileocaecal segment 3 months after side-to-side ileotransversostomy, which was performed from adhesion-obstruction after duodenolysis for malrotation I and CDO. Both the blind pouch- and the blind loop-deformation were resected and the children recovered well. To avoid blind pouch- and blind loop-deformations in the intestines, the anastomosis must be made wide enough, and especially in the surgery of the jejuno-ileo-colic region an end-to-end anastomosis is preferable.", "contents": "Intestinal blind pouch- and blind loop-syndrome in children operated previously for congenital duodenal obstruction. A follow-up study of 27 children operated for congenital duodenal obstruction (CDO) in years 1953-71 is presented. Nine children belonged to the intrinsic and 18 children to the extrinsic group of CDO. A total of 7 retrocolic, isoperistaltic, side-to-side duodeno-jejunostomy, 7 Ladd's operation, 8 duodenolysis, 2 reduction of midgut volvulus, 2 duodenostomy a.m. Morton and one gastro-jejunostomy were performed at the age of 1 day-15 years. The clinical and radiological examinations were performed 3-21 years (mean 10 years 2 months) after these operations. In 3 cases there was a moderate duodenal dilation, but reoperation was not necessary. During the follow-up period, one boy, now aged 8 years, developed a blind pouch-syndrome in the I portion of the duodenum containing a 5 X 5 cm phytobezoar 4 1/2 years after duodeno-jejunostomy. The frequency of blind pouch-syndrome after duodeno-jejunostomy was thus 1:7 or 14%. One girl, now aged 9 years, developed a blind loop-syndrome in the ileocaecal segment 3 months after side-to-side ileotransversostomy, which was performed from adhesion-obstruction after duodenolysis for malrotation I and CDO. Both the blind pouch- and the blind loop-deformation were resected and the children recovered well. To avoid blind pouch- and blind loop-deformations in the intestines, the anastomosis must be made wide enough, and especially in the surgery of the jejuno-ileo-colic region an end-to-end anastomosis is preferable."} {"id": "PMID:1267408", "title": "A benign hepatocellular adenoma treated by extended right lobectomy.", "content": "A 19-YEAR-OLD WOMAN WITH A LARGE BENIGN HEPATOCELLULAR ADENOMA IS PRESENTED. The initial symptom was continuous anaemia demanding transfusions twice a month. Coeliac angiography revealed the hepatic tumour, which was thought to be malignant. Angiography produced permanent paraplegia as a complication. The tumour was radically removed by an extended right lobectomy. The weight of the operation specimen was 2200 g. Histologically the differential diagnosis layed between benign hepatocellular adenoma and hepatocellular carcinoma. Postoperative stricture of the common duct developed as a complication of T-tube and was successfully treated at reoperation. Liver function became totally restored after the operation and after 5 years' follow-up there has been no tumour recurrence. The very rare benign hepatocellular adenomas are discussed.", "contents": "A benign hepatocellular adenoma treated by extended right lobectomy. A 19-YEAR-OLD WOMAN WITH A LARGE BENIGN HEPATOCELLULAR ADENOMA IS PRESENTED. The initial symptom was continuous anaemia demanding transfusions twice a month. Coeliac angiography revealed the hepatic tumour, which was thought to be malignant. Angiography produced permanent paraplegia as a complication. The tumour was radically removed by an extended right lobectomy. The weight of the operation specimen was 2200 g. Histologically the differential diagnosis layed between benign hepatocellular adenoma and hepatocellular carcinoma. Postoperative stricture of the common duct developed as a complication of T-tube and was successfully treated at reoperation. Liver function became totally restored after the operation and after 5 years' follow-up there has been no tumour recurrence. The very rare benign hepatocellular adenomas are discussed."} {"id": "PMID:1267409", "title": "Short-stay varicose vein surgery.", "content": "From 1967 patients attending for varicose vein surgery at the Meilahti Hospital Helsinki University Central Hospital, have been operated on on the day of admission, spend the following night in the bed ward and are discharged the morning after the operation. The operation is performed under general anaesthesia with as radical approach as possible stripping the long saphenous vein and, if required, the short saphenous vein, excising the superficial side branches and ligating incompetent perforators. In the study a follow-up examination was carried out on 2334 patients. Wound infections occurred in 1.8%. Two patients had transient arrhytmia, and one a late haemorrhage. More serious complications were absent. During the follow-up period 5.2% of patients were operated on for recurrent varicose veins. 84.6% were subjectively satisfied. The number of hospital days per patient averaged 1.2. It was possible to follow the above planned course of action in 93.4%. The organization and surgical technique can be recommended in order to achieve savings in hospital days and to produce permanent and good surgical results.", "contents": "Short-stay varicose vein surgery. From 1967 patients attending for varicose vein surgery at the Meilahti Hospital Helsinki University Central Hospital, have been operated on on the day of admission, spend the following night in the bed ward and are discharged the morning after the operation. The operation is performed under general anaesthesia with as radical approach as possible stripping the long saphenous vein and, if required, the short saphenous vein, excising the superficial side branches and ligating incompetent perforators. In the study a follow-up examination was carried out on 2334 patients. Wound infections occurred in 1.8%. Two patients had transient arrhytmia, and one a late haemorrhage. More serious complications were absent. During the follow-up period 5.2% of patients were operated on for recurrent varicose veins. 84.6% were subjectively satisfied. The number of hospital days per patient averaged 1.2. It was possible to follow the above planned course of action in 93.4%. The organization and surgical technique can be recommended in order to achieve savings in hospital days and to produce permanent and good surgical results."} {"id": "PMID:1267410", "title": "A comparison of dicloxacillin and ampicillin in the antibiotic prophylaxis of total hip replacement.", "content": "The effect of two semi-synthetic penicillins, dicloxacillin and ampicillin was compared in systemic antibiotic prophylaxis in total hip replacement patients. The drugs were given in routine oral dosage for eight days to two patient groups each consisting of 50 patients. There was no fatality. In the ampicillin group there were three staphylococcal infections but no infections in the dicloxacillin group. Two of the infections occurred in reapplication cases leading to the loosening of the prosthesis. One infection appeared after a primary operation with a superficial recurrence 10 months later. In the ampicillin group, side effects were diagnosed in 12 cases and in the dicloxacillin group in one case.", "contents": "A comparison of dicloxacillin and ampicillin in the antibiotic prophylaxis of total hip replacement. The effect of two semi-synthetic penicillins, dicloxacillin and ampicillin was compared in systemic antibiotic prophylaxis in total hip replacement patients. The drugs were given in routine oral dosage for eight days to two patient groups each consisting of 50 patients. There was no fatality. In the ampicillin group there were three staphylococcal infections but no infections in the dicloxacillin group. Two of the infections occurred in reapplication cases leading to the loosening of the prosthesis. One infection appeared after a primary operation with a superficial recurrence 10 months later. In the ampicillin group, side effects were diagnosed in 12 cases and in the dicloxacillin group in one case."} {"id": "PMID:1267411", "title": "Plasma calcium levels in pregnant Asian women.", "content": "Plasma calcium, phosphorus, alkaline phosphatase, total protein, and albumin were measured during pregnancy in a group of Asian women living in the south of England and in a control group. The Asian women had slightly lower mean plasma calcium concentrations than the control group. Exposure of Asian women to sunshine appeared to be low, and it was inferred that they probably had little endogenous synthesis of cholecalciferol as a result. Both Asian and control subjects ingested similarly low amounts of vitamin D. The Asian women consumed greater amounts of phytate and vegetable fibres than the controls, and it is suggested that these substances may reduce absorption of insoluble lipids (including cholecalciferol) and calcium in a setting where the dietary intake and endogenous synthesis of vitamin D are already borderline for the subject's requirements.", "contents": "Plasma calcium levels in pregnant Asian women. Plasma calcium, phosphorus, alkaline phosphatase, total protein, and albumin were measured during pregnancy in a group of Asian women living in the south of England and in a control group. The Asian women had slightly lower mean plasma calcium concentrations than the control group. Exposure of Asian women to sunshine appeared to be low, and it was inferred that they probably had little endogenous synthesis of cholecalciferol as a result. Both Asian and control subjects ingested similarly low amounts of vitamin D. The Asian women consumed greater amounts of phytate and vegetable fibres than the controls, and it is suggested that these substances may reduce absorption of insoluble lipids (including cholecalciferol) and calcium in a setting where the dietary intake and endogenous synthesis of vitamin D are already borderline for the subject's requirements."} {"id": "PMID:1267412", "title": "A potential screening test for elevated serum amylase levels: preliminary communication.", "content": "The use of an amylase-sensitive paper in a screening test for elevated serum amylase levels is described. The paper requires some modification before it can be used as a quantitative amylase assay, but even in its present form it will reliably identify samples with raised amylase levels. In tests with sera received routinely for amylase assay the paper characterised 80% of samples as Normal. Quantitative amylase assay confirmed the results, and thus, even with the present paper, if only the Medium or High sera were sent to the laboratory for full biochemical analysis there would be an 80% decrease in requests.", "contents": "A potential screening test for elevated serum amylase levels: preliminary communication. The use of an amylase-sensitive paper in a screening test for elevated serum amylase levels is described. The paper requires some modification before it can be used as a quantitative amylase assay, but even in its present form it will reliably identify samples with raised amylase levels. In tests with sera received routinely for amylase assay the paper characterised 80% of samples as Normal. Quantitative amylase assay confirmed the results, and thus, even with the present paper, if only the Medium or High sera were sent to the laboratory for full biochemical analysis there would be an 80% decrease in requests."} {"id": "PMID:1267413", "title": "Preparation of 125I-thyroxine and 125I-triiodothyronine of high specific activity for the radioimmunoassay of serum total T4 and T3.", "content": "A simple and inexpensive procedure for the preparation of high specific activity 125I radioiodinated triiodothyronine and thyroxine is described. The specific activities achieved are approximately 350 Ci/g for 125I-T4, and either 200 Ci/g for 125I-T3 depending on the reagents employed. The high specific activity 125I-T4 and 125I-T3 are suitable for the routine radioimmunoassay of serum total T3 and T4. When properly stored they have a self life of at least seven weeks.", "contents": "Preparation of 125I-thyroxine and 125I-triiodothyronine of high specific activity for the radioimmunoassay of serum total T4 and T3. A simple and inexpensive procedure for the preparation of high specific activity 125I radioiodinated triiodothyronine and thyroxine is described. The specific activities achieved are approximately 350 Ci/g for 125I-T4, and either 200 Ci/g for 125I-T3 depending on the reagents employed. The high specific activity 125I-T4 and 125I-T3 are suitable for the routine radioimmunoassay of serum total T3 and T4. When properly stored they have a self life of at least seven weeks."} {"id": "PMID:1267424", "title": "Trimethoprim-sulfamethoxazole in murine toxoplasmosis.", "content": "The combination trimethoprim-sulfamethoxazole had no greater activity in a murine model of toxoplasmosis than did sulfamethoxazole alone.", "contents": "Trimethoprim-sulfamethoxazole in murine toxoplasmosis. The combination trimethoprim-sulfamethoxazole had no greater activity in a murine model of toxoplasmosis than did sulfamethoxazole alone."} {"id": "PMID:1267425", "title": "Antiviral activity of 10-carboxymethyl-9-acridanone.", "content": "Intraperitoneal administration of 10-carboxymethyl-9-acridanone sodium salt (CMA) protected at least 50% of mice tested from otherwise lethal infections with Semliki forest, coxsackie B1, Columbia SK, Western equine encephalitis, herpes simplex, and pseudorabies viruses. The protective effect against influenza A2/Asian/J305 and coxsackie A21 viruses was less but was statistically significant. When administered either subcutaneously or orally, CMA protected at least 50% of mice against Semliki forest and pseudorabies viruses; the effect against coxsackie B1 and herpes simplex viruses was less but was statistically significant. Initiation of treatment could be delayed from 2 to 24 h after infection of mice with coxsackie B1, herpes simplex, Semliki forest, and Western equine encephalitis viruses without loss of an antiviral effect. CMA did not inactivate Semliki forest or coxsackie B1 viruses on contact and was without effect against any of the viruses tested in tissue culture by the tube dilution assay. The humoral antibody response in mice to both influenza virus and sheep erythrocytes was unaffected by CMA. After administration of CMA, an interferon-like substance was induced in mice or mouse cell culture but not in rabbits or rabbit cell culture.", "contents": "Antiviral activity of 10-carboxymethyl-9-acridanone. Intraperitoneal administration of 10-carboxymethyl-9-acridanone sodium salt (CMA) protected at least 50% of mice tested from otherwise lethal infections with Semliki forest, coxsackie B1, Columbia SK, Western equine encephalitis, herpes simplex, and pseudorabies viruses. The protective effect against influenza A2/Asian/J305 and coxsackie A21 viruses was less but was statistically significant. When administered either subcutaneously or orally, CMA protected at least 50% of mice against Semliki forest and pseudorabies viruses; the effect against coxsackie B1 and herpes simplex viruses was less but was statistically significant. Initiation of treatment could be delayed from 2 to 24 h after infection of mice with coxsackie B1, herpes simplex, Semliki forest, and Western equine encephalitis viruses without loss of an antiviral effect. CMA did not inactivate Semliki forest or coxsackie B1 viruses on contact and was without effect against any of the viruses tested in tissue culture by the tube dilution assay. The humoral antibody response in mice to both influenza virus and sheep erythrocytes was unaffected by CMA. After administration of CMA, an interferon-like substance was induced in mice or mouse cell culture but not in rabbits or rabbit cell culture."} {"id": "PMID:1267426", "title": "Antimicrobial susceptibilities of shigellae isolated in Houston, Texas, in 1974.", "content": "One hundred seventy-three strains of shigellae (113 Shigella sonnei, 56 S. flexneri, and four others) isolated in Houston during 1974 were tested for susceptibility to commonly used and newer antimicrobial agents. Forty-five percent of S. sonnei strains were susceptible to ampicillin, whereas 93% of S. flexneri strains were susceptible to that agent. S. sonnei and S. flexneri strains were equally susceptible to tetracycline (35 and 33%, respectively). All 173 strains were uniformly susceptible to quinoline drugs (cinoxacin, oxolinic acid, and nalidixic acid) and to trimethoprim-sulfamethoxazole. This study supports recent suggestions that the initial therapy of bacillary dysentery no longer should be ampicillin or tetracycline. It remains for field testing to determine whether quinoline agents or trimethoprim-sulfamethoxazole will be the treatment of choice.", "contents": "Antimicrobial susceptibilities of shigellae isolated in Houston, Texas, in 1974. One hundred seventy-three strains of shigellae (113 Shigella sonnei, 56 S. flexneri, and four others) isolated in Houston during 1974 were tested for susceptibility to commonly used and newer antimicrobial agents. Forty-five percent of S. sonnei strains were susceptible to ampicillin, whereas 93% of S. flexneri strains were susceptible to that agent. S. sonnei and S. flexneri strains were equally susceptible to tetracycline (35 and 33%, respectively). All 173 strains were uniformly susceptible to quinoline drugs (cinoxacin, oxolinic acid, and nalidixic acid) and to trimethoprim-sulfamethoxazole. This study supports recent suggestions that the initial therapy of bacillary dysentery no longer should be ampicillin or tetracycline. It remains for field testing to determine whether quinoline agents or trimethoprim-sulfamethoxazole will be the treatment of choice."} {"id": "PMID:1267427", "title": "Novel mechanism of resistance to folate analogues: ribonucleoside diphosphate reductase deficiency in bacteriophage T4.", "content": "Some spontaneously occurring bacteriophage T4 mutants (far mutants) were able to form plaques in the presence of concentrations of folate analogues that completely inhibit plaque formation by wild-type phage T4. Some of these far mutants were shown to be ribonucleoside diphosphate (RDP) reductase (EC 1.17.4.1) deficient, and some independently isolated RDP reductase-deficient mutants (nrd mutants) were shown to be folate analogue resistant. The map positions of the RDP reductase-deficient far mutants were shown to be within the genes controlling the phage-induced RDP reductase activity.", "contents": "Novel mechanism of resistance to folate analogues: ribonucleoside diphosphate reductase deficiency in bacteriophage T4. Some spontaneously occurring bacteriophage T4 mutants (far mutants) were able to form plaques in the presence of concentrations of folate analogues that completely inhibit plaque formation by wild-type phage T4. Some of these far mutants were shown to be ribonucleoside diphosphate (RDP) reductase (EC 1.17.4.1) deficient, and some independently isolated RDP reductase-deficient mutants (nrd mutants) were shown to be folate analogue resistant. The map positions of the RDP reductase-deficient far mutants were shown to be within the genes controlling the phage-induced RDP reductase activity."} {"id": "PMID:1267428", "title": "Effect of cerulenin on growth and lipid metabolism of mycoplasmas.", "content": "Cerulenin markedly inhibited the growth of Acholeplasma laidlawii. A. axanthum and A. granularum were less susceptible, whereas the sterol-requiring Mycoplasma species examined showed very little susceptibility. The inhibition was not reversed by the addition of long-chain fatty acids to the medium. At a concentration of 20 mug/ml, cerulenin inhibited the incorporation of [(14)C]acetate into A. laidlawii membrane lipids, but it had no effect on either protein or nucleic acid biosynthesis. Cerulenin inhibited both the de novo synthesis of long-chain fatty acids and the elongation of medium-chain fatty acids. As a result, carotenoid biosynthesis was stimulated, and increased amounts of oleic and elaidic acids were incorporated into membrane polar lipids. Our studies support the concept that cerulenin can serve as a useful tool for obtaining better control of fatty acid composition of A. laidlawii membranes.", "contents": "Effect of cerulenin on growth and lipid metabolism of mycoplasmas. Cerulenin markedly inhibited the growth of Acholeplasma laidlawii. A. axanthum and A. granularum were less susceptible, whereas the sterol-requiring Mycoplasma species examined showed very little susceptibility. The inhibition was not reversed by the addition of long-chain fatty acids to the medium. At a concentration of 20 mug/ml, cerulenin inhibited the incorporation of [(14)C]acetate into A. laidlawii membrane lipids, but it had no effect on either protein or nucleic acid biosynthesis. Cerulenin inhibited both the de novo synthesis of long-chain fatty acids and the elongation of medium-chain fatty acids. As a result, carotenoid biosynthesis was stimulated, and increased amounts of oleic and elaidic acids were incorporated into membrane polar lipids. Our studies support the concept that cerulenin can serve as a useful tool for obtaining better control of fatty acid composition of A. laidlawii membranes."} {"id": "PMID:1267429", "title": "Phosphonoacetic acid in the treatment of experimental ocular herpes simplex infections.", "content": "Phosphonoacetic acid had a significant antiviral effect when applied topically, both in liquid and ointment preparations, on superficial herpetic keratitis in rabbits and was equally as effective as idoxuridine. It was also effective in the treatment of idoxuridine-resistant herpetic keratitis. Phosphonoacetic acid was not effective in the treatment of experimental herpetic iritis when applied topically but was significantly effective when administered intravenously and subconjunctivally. No significant local or systemic toxicity was encountered.", "contents": "Phosphonoacetic acid in the treatment of experimental ocular herpes simplex infections. Phosphonoacetic acid had a significant antiviral effect when applied topically, both in liquid and ointment preparations, on superficial herpetic keratitis in rabbits and was equally as effective as idoxuridine. It was also effective in the treatment of idoxuridine-resistant herpetic keratitis. Phosphonoacetic acid was not effective in the treatment of experimental herpetic iritis when applied topically but was significantly effective when administered intravenously and subconjunctivally. No significant local or systemic toxicity was encountered."} {"id": "PMID:1267430", "title": "Hyperbaric oxygen exposures for intrahepatic abscesses produced in mice by nonsporeforming anaerobic bacteria.", "content": "Hyperbaric oxygen exposures were evaluated for treatment of progressive liver abscesses produced by intraperitoneal injection of combined cultures of Fusobacterium necrophorum plus either Bacteroides fragilis subsp. fragilis or Fusobacterium nucleatum in a mouse model. Infected control and hyperbaric oxygen-exposed mice were autopsied 5 or 6 weeks after inoculation of bacteria and were assigned numerical pathology scores according to the number and size of abscesses present. Seventeen daily 3-h exposures to 100% O(2) at 2 atmospheres absolute pressure begun either 1 day or 1 week after injection of bacteria significantly reduced the number and size of abscesses among mice infected with either mixture of anaerobic organisms. Abscesses due to mixed fusobacteria were often completely resolved. These data support the efficacy of hyperbaric oxygen for treatment of mixed anaerobic infection produced by Bacteroides and Fusobacterium species and suggest its further evaluation as a potential alternate or adjunct to present therapy for certain types of serious anaerobic infection.", "contents": "Hyperbaric oxygen exposures for intrahepatic abscesses produced in mice by nonsporeforming anaerobic bacteria. Hyperbaric oxygen exposures were evaluated for treatment of progressive liver abscesses produced by intraperitoneal injection of combined cultures of Fusobacterium necrophorum plus either Bacteroides fragilis subsp. fragilis or Fusobacterium nucleatum in a mouse model. Infected control and hyperbaric oxygen-exposed mice were autopsied 5 or 6 weeks after inoculation of bacteria and were assigned numerical pathology scores according to the number and size of abscesses present. Seventeen daily 3-h exposures to 100% O(2) at 2 atmospheres absolute pressure begun either 1 day or 1 week after injection of bacteria significantly reduced the number and size of abscesses among mice infected with either mixture of anaerobic organisms. Abscesses due to mixed fusobacteria were often completely resolved. These data support the efficacy of hyperbaric oxygen for treatment of mixed anaerobic infection produced by Bacteroides and Fusobacterium species and suggest its further evaluation as a potential alternate or adjunct to present therapy for certain types of serious anaerobic infection."} {"id": "PMID:1267431", "title": "Relative morphological effects induced by cefoxitin and other beta-lactam antibiotics in vitro.", "content": "Cefoxitin, a new semisynthetic cephamycin antibiotic, induced filament formation at subinhibitory concentrations with a beta-lactamaseless strain of Enterobacter cloacae (HSC 18410 M66). The extent of filament induction by cefoxitin was similar to that seen with cephalothin, cefazolin, and benzylpenicillin. Filament induction by cefoxitin was markedly less than that seen with cephalexin, carbenicillin, ticarcillin, cephradine, and cephapirin. Antibiotics which failed to induce filaments at any level tested included cephaloridine, cephacetrile, cephalosporin C, the cephamycins, 6-aminopenicillanic acid, 7-aminocephalosporanic acid, A16884, A16886, and FL-1060. Those antimicrobial agents tested which lacked an aromatic substituent in the 7-position (for cephems) or in the 6-position (for penams) did not induce filaments. These observations suggest a possible relationship between filament induction of the test organism and the molecular nature of constituents in the 7- or 6-position of beta-lactams.", "contents": "Relative morphological effects induced by cefoxitin and other beta-lactam antibiotics in vitro. Cefoxitin, a new semisynthetic cephamycin antibiotic, induced filament formation at subinhibitory concentrations with a beta-lactamaseless strain of Enterobacter cloacae (HSC 18410 M66). The extent of filament induction by cefoxitin was similar to that seen with cephalothin, cefazolin, and benzylpenicillin. Filament induction by cefoxitin was markedly less than that seen with cephalexin, carbenicillin, ticarcillin, cephradine, and cephapirin. Antibiotics which failed to induce filaments at any level tested included cephaloridine, cephacetrile, cephalosporin C, the cephamycins, 6-aminopenicillanic acid, 7-aminocephalosporanic acid, A16884, A16886, and FL-1060. Those antimicrobial agents tested which lacked an aromatic substituent in the 7-position (for cephems) or in the 6-position (for penams) did not induce filaments. These observations suggest a possible relationship between filament induction of the test organism and the molecular nature of constituents in the 7- or 6-position of beta-lactams."} {"id": "PMID:1267432", "title": "Rosamicin: in vitro activity against anaerobes and comparison with erythromycin.", "content": "The in vitro activity of rosamicin was determined against 231 strains of anaerobic bacteria and compared with the activity of erythromycin against the same strains. Rosamicin and erythromycin had similar activity against strains of Peptostreptococcus and gram-positive nonsporeforming bacilli. Rosamicin was somewhat more active against strains of Peptococcus, Clostridium, and gram-negative anaerobes. All strains of Bacteroides fragilis tested were inhibited by 4 mug of rosamicin or less per ml, whereas only 76% of them were inhibited by this concentration of erythromycin. Rosamicin was distinctly more active against Fusobacterium nucleatum. Because of its in vitro activity, further investigation of the pharmacology of this drug is warranted.", "contents": "Rosamicin: in vitro activity against anaerobes and comparison with erythromycin. The in vitro activity of rosamicin was determined against 231 strains of anaerobic bacteria and compared with the activity of erythromycin against the same strains. Rosamicin and erythromycin had similar activity against strains of Peptostreptococcus and gram-positive nonsporeforming bacilli. Rosamicin was somewhat more active against strains of Peptococcus, Clostridium, and gram-negative anaerobes. All strains of Bacteroides fragilis tested were inhibited by 4 mug of rosamicin or less per ml, whereas only 76% of them were inhibited by this concentration of erythromycin. Rosamicin was distinctly more active against Fusobacterium nucleatum. Because of its in vitro activity, further investigation of the pharmacology of this drug is warranted."} {"id": "PMID:1267433", "title": "Unreliability of direct antibiotic susceptibility testing on wound exudates.", "content": "Direct susceptibility testing was performed on 110 specimens of wound exudates. Growth was inadequate in 76 of these specimens. Of the remaining 34 specimens, only 5 produced results corresponding to those obtained by testing individual bacterial isolates by the Kirby-Bauer technique. This study confirms that direct susceptibility testing of wound exudates may provide misleading and clinically unreliable information on more than 95% of specimens.", "contents": "Unreliability of direct antibiotic susceptibility testing on wound exudates. Direct susceptibility testing was performed on 110 specimens of wound exudates. Growth was inadequate in 76 of these specimens. Of the remaining 34 specimens, only 5 produced results corresponding to those obtained by testing individual bacterial isolates by the Kirby-Bauer technique. This study confirms that direct susceptibility testing of wound exudates may provide misleading and clinically unreliable information on more than 95% of specimens."} {"id": "PMID:1267434", "title": "Peritoneal transfer of thiamphenicol during peritoneal dialysis.", "content": "The pharmacokinetics of thiamphenicol (TAP) was studied in 17 functionally anephric patients during peritoneal dialysis. Eleven patients were given single intramuscular injections of TAP in doses of 10 to 20 mg/kg of body weight. After this, serial blood samples and outflow dialysate collections were assayed for TAP by gas chromatography. The mean overall elimination rate constant was 0.036 +/- 0.007/h, the serum half time was 8.4 h, and the apparent volume of distribution was 71.0% (+/-14.39%) of the body weight. These parameters were not significantly different from those determined in anephric patients not on dialysis. The mean recovery of the administered TAP doses in the pooled outflow dialysate was 7.7% (+/-2.76%) over 22 h. In six other patients TAP was added to the inflow dialysate in concentrations of 10 to 20 mg/liter for 22 h. Throughout the dialysis periods, serum TAP levels did not rise above 4 mug/ml in transfer of TAP.", "contents": "Peritoneal transfer of thiamphenicol during peritoneal dialysis. The pharmacokinetics of thiamphenicol (TAP) was studied in 17 functionally anephric patients during peritoneal dialysis. Eleven patients were given single intramuscular injections of TAP in doses of 10 to 20 mg/kg of body weight. After this, serial blood samples and outflow dialysate collections were assayed for TAP by gas chromatography. The mean overall elimination rate constant was 0.036 +/- 0.007/h, the serum half time was 8.4 h, and the apparent volume of distribution was 71.0% (+/-14.39%) of the body weight. These parameters were not significantly different from those determined in anephric patients not on dialysis. The mean recovery of the administered TAP doses in the pooled outflow dialysate was 7.7% (+/-2.76%) over 22 h. In six other patients TAP was added to the inflow dialysate in concentrations of 10 to 20 mg/liter for 22 h. Throughout the dialysis periods, serum TAP levels did not rise above 4 mug/ml in transfer of TAP."} {"id": "PMID:1267435", "title": "Pipemidic acid: its activities against various experimental infections.", "content": "Pipemidic acid, a structural relative of piromidic and nalidixic acids, exhibited substantial therapeutic activity when it was administered orally to mice bearing either widely disseminated or relatively localized infections with Staphylococcus aureus and a variety of gram-negative bacilli. The activity of pipemidic acid was always greater than that of piromidic and nalidixic acids; in infections with Pseudomonas aeruginosa and in bacilli resistant to the latter two drugs, pipemidic acid exhibited significant activity. In limited comparative studies, the activities of pipemidic acid were generally superior to the activities of cephalexin, ampicillin, and carbenicillin. Gentamicin, administered subcutaneously, was more active than pipemidic acid, given either orally or subcutaneously, against both systemic and localized infections with P. aeruginosa. The therapeutic accomplishments of pipemidic acid were attained with well-tolerated doses.", "contents": "Pipemidic acid: its activities against various experimental infections. Pipemidic acid, a structural relative of piromidic and nalidixic acids, exhibited substantial therapeutic activity when it was administered orally to mice bearing either widely disseminated or relatively localized infections with Staphylococcus aureus and a variety of gram-negative bacilli. The activity of pipemidic acid was always greater than that of piromidic and nalidixic acids; in infections with Pseudomonas aeruginosa and in bacilli resistant to the latter two drugs, pipemidic acid exhibited significant activity. In limited comparative studies, the activities of pipemidic acid were generally superior to the activities of cephalexin, ampicillin, and carbenicillin. Gentamicin, administered subcutaneously, was more active than pipemidic acid, given either orally or subcutaneously, against both systemic and localized infections with P. aeruginosa. The therapeutic accomplishments of pipemidic acid were attained with well-tolerated doses."} {"id": "PMID:1267436", "title": "Effect of cephalothin on renal cortical concentrations of gentamicin in rats.", "content": "Renal cortical concentrations of gentamicin were significantly lower in rats given this aminoglycoside and cephalothin simultaneously than in animals given gentamicin alone. This effect may be responsible, in part, for the reduction in nephrotoxicity reported previously in animals given the combination of drugs.", "contents": "Effect of cephalothin on renal cortical concentrations of gentamicin in rats. Renal cortical concentrations of gentamicin were significantly lower in rats given this aminoglycoside and cephalothin simultaneously than in animals given gentamicin alone. This effect may be responsible, in part, for the reduction in nephrotoxicity reported previously in animals given the combination of drugs."} {"id": "PMID:1267437", "title": "Minocycline resistance in Staphylococcus aureus: effect on phage susceptibility.", "content": "Tetracycline-resistant strains of Staphylococcus aureus are minocycline sensitive, with the exception of strains susceptible to phages of the 83A/84/85 complex and some methicillin-resistant strains of other phage types. Strains of the 83A/84/85 complex yield mutants with increased minocycline resistance. Transduction of minocycline resistance into the susceptible strain RN 450 was obtained with donor strains possessing either markers for both extrachromosomal tetracycline resistance (tet) and chromosomal tetracycline + minocycline resistance (tmn R), or only for chromosomal tmn R resistance. The chromosomal marker was differentiated from the extrachromosomal marker by the lack of detectable extrachromosomal deoxyribonucleic acid after transfer into strain RN 450, transfer into a rec(+) strain, lack of transfer into rec(-) acceptor strain, and cotransduction with chromosomal determinants for guanine biosynthesis. Both chromosomal and extrachromosomal tetracycline resistance can be induced by tetracycline. Induction by tetracycline of chromosomal tetracycline resistance resulted in simultaneous induction of minocycline resistance. The mutation toward increased minocycline resistance (tmn --> tmn R) is a regulatory mutation toward constitutivity or semiconstitutivity. Constitutive resistance is dominant in tmn R/tet diploids. Transfer of the tet marker does not affect the phage susceptibility of the acceptor strain. The tmn R marker, originating from donor strains of the 83A/84/85 complex, renders strain RN 450 resistant to several typing phages, with the exception of phages of the 83A/84/85 complex. This could possibly account for the phage typing patterns of minocycline-resistant staphylococci.", "contents": "Minocycline resistance in Staphylococcus aureus: effect on phage susceptibility. Tetracycline-resistant strains of Staphylococcus aureus are minocycline sensitive, with the exception of strains susceptible to phages of the 83A/84/85 complex and some methicillin-resistant strains of other phage types. Strains of the 83A/84/85 complex yield mutants with increased minocycline resistance. Transduction of minocycline resistance into the susceptible strain RN 450 was obtained with donor strains possessing either markers for both extrachromosomal tetracycline resistance (tet) and chromosomal tetracycline + minocycline resistance (tmn R), or only for chromosomal tmn R resistance. The chromosomal marker was differentiated from the extrachromosomal marker by the lack of detectable extrachromosomal deoxyribonucleic acid after transfer into strain RN 450, transfer into a rec(+) strain, lack of transfer into rec(-) acceptor strain, and cotransduction with chromosomal determinants for guanine biosynthesis. Both chromosomal and extrachromosomal tetracycline resistance can be induced by tetracycline. Induction by tetracycline of chromosomal tetracycline resistance resulted in simultaneous induction of minocycline resistance. The mutation toward increased minocycline resistance (tmn --> tmn R) is a regulatory mutation toward constitutivity or semiconstitutivity. Constitutive resistance is dominant in tmn R/tet diploids. Transfer of the tet marker does not affect the phage susceptibility of the acceptor strain. The tmn R marker, originating from donor strains of the 83A/84/85 complex, renders strain RN 450 resistant to several typing phages, with the exception of phages of the 83A/84/85 complex. This could possibly account for the phage typing patterns of minocycline-resistant staphylococci."} {"id": "PMID:1267438", "title": "Significant reduction in the incidence of phlebitis with buffered versus unbuffered cephalothin.", "content": "Cephalothin (1 g every 2 h), buffered cephalothin, and diluent alone (5% dextrose in water) were each administered for 4 days intravenously to 12 volunteers in a double-blind crossover study. The incidence of phlebitis with buffered cephalothin was significantly lower than that with unbuffered drug (P < 0.01) and almost identical to the incidence with diluent alone.", "contents": "Significant reduction in the incidence of phlebitis with buffered versus unbuffered cephalothin. Cephalothin (1 g every 2 h), buffered cephalothin, and diluent alone (5% dextrose in water) were each administered for 4 days intravenously to 12 volunteers in a double-blind crossover study. The incidence of phlebitis with buffered cephalothin was significantly lower than that with unbuffered drug (P < 0.01) and almost identical to the incidence with diluent alone."} {"id": "PMID:1267439", "title": "In vitro susceptibility comparisons and recommendations for oxolinic acid.", "content": "Minimal inhibitory concentration and disk diffusion susceptibility studies were carried out with oxolinic acid to determine a recommended disk content for disk susceptibility testing. Regression curve analyses were performed with disks containing 1, 2, and 5 mug of oxolinic acid. Data suggest that the 5-mug disk more satisfactorily fulfills requirements for susceptibility testing than the 1- or 2-mug disks evaluated. Ultraviolet spectral analysis studies for absorption maxima and extinction coefficients were done to verify the authenticity and concentration of oxolinic acid in the aqueous solutions studied.", "contents": "In vitro susceptibility comparisons and recommendations for oxolinic acid. Minimal inhibitory concentration and disk diffusion susceptibility studies were carried out with oxolinic acid to determine a recommended disk content for disk susceptibility testing. Regression curve analyses were performed with disks containing 1, 2, and 5 mug of oxolinic acid. Data suggest that the 5-mug disk more satisfactorily fulfills requirements for susceptibility testing than the 1- or 2-mug disks evaluated. Ultraviolet spectral analysis studies for absorption maxima and extinction coefficients were done to verify the authenticity and concentration of oxolinic acid in the aqueous solutions studied."} {"id": "PMID:1267440", "title": "Effect of diethylpyrocarbonate on the antiviral and interferon-inducing activities of viral and nonviral agents.", "content": "Diethylpyrocarbonate (DEPC) treatment of interferon (IF) inducers was studied both in vitro and in vivo. DEPC did not affect the antiviral activity of poly(I.C), statolon, or reovirus in cultured chicken embryo fibroblast cells, but the activities of poly(I.C), statolon, and MU9 replicative form in cultured mouse embryo cells were markedly reduced by the treatment. Target-organ treatment of Swiss Webster mice with DEPC-treated poly(I.C) produced higher levels of serum IF than did the same procedure with untreated poly(I.C), but the animals were not protected against vaccinial encephalitis. In contrast, DEPC-treated statolon protected the animals, although the peak serum IF level was significantly lower than in those treated with intact statolon. Nevertheless, the antiviral activity of statolon was also found to be mediated by IF, since no activity was seen in Vero cells. DEPC-treated single-stranded ribonucleic acid viruses failed to stimulate IF production, indicating that some viral factor(s) susceptible to DEPC is required for the stimulation observed with untreated viruses.", "contents": "Effect of diethylpyrocarbonate on the antiviral and interferon-inducing activities of viral and nonviral agents. Diethylpyrocarbonate (DEPC) treatment of interferon (IF) inducers was studied both in vitro and in vivo. DEPC did not affect the antiviral activity of poly(I.C), statolon, or reovirus in cultured chicken embryo fibroblast cells, but the activities of poly(I.C), statolon, and MU9 replicative form in cultured mouse embryo cells were markedly reduced by the treatment. Target-organ treatment of Swiss Webster mice with DEPC-treated poly(I.C) produced higher levels of serum IF than did the same procedure with untreated poly(I.C), but the animals were not protected against vaccinial encephalitis. In contrast, DEPC-treated statolon protected the animals, although the peak serum IF level was significantly lower than in those treated with intact statolon. Nevertheless, the antiviral activity of statolon was also found to be mediated by IF, since no activity was seen in Vero cells. DEPC-treated single-stranded ribonucleic acid viruses failed to stimulate IF production, indicating that some viral factor(s) susceptible to DEPC is required for the stimulation observed with untreated viruses."} {"id": "PMID:1267441", "title": "Antibacterial activity of cefuroxime, a new cephalosporin antibiotic, compared with that of cephaloridine, cephalothin, and cefamandole.", "content": "The in vitro activity of cefuroxime, a new cephalosporin derivative, was compared with that of cephaloridine, cephalothin, and cefamandole against strains of gram-positive and gram-negative bacteria recently isolated from clinical sources. Cefuroxime showed very similar activity to cefamandole against Staphylococcus aureus, Haemophilus influenzae, and most members of the Enterobacteriaceae. It was more active than cefamandole against gonococci, pneumococci, and most streptococci. Increasing the inoculum size appeared to have less effect on the minimum inhibitory concentrations of cefuroxime for gram-negative bacilli than has been found with the other cephalosporin derivatives, and minimum bactericidal concentrations of cefuroxime were only marginally greater than minimum inhibitory concentrations.", "contents": "Antibacterial activity of cefuroxime, a new cephalosporin antibiotic, compared with that of cephaloridine, cephalothin, and cefamandole. The in vitro activity of cefuroxime, a new cephalosporin derivative, was compared with that of cephaloridine, cephalothin, and cefamandole against strains of gram-positive and gram-negative bacteria recently isolated from clinical sources. Cefuroxime showed very similar activity to cefamandole against Staphylococcus aureus, Haemophilus influenzae, and most members of the Enterobacteriaceae. It was more active than cefamandole against gonococci, pneumococci, and most streptococci. Increasing the inoculum size appeared to have less effect on the minimum inhibitory concentrations of cefuroxime for gram-negative bacilli than has been found with the other cephalosporin derivatives, and minimum bactericidal concentrations of cefuroxime were only marginally greater than minimum inhibitory concentrations."} {"id": "PMID:1267442", "title": "Synergy of mecillinam (FL1060) with penicillins and cephalosporins against Proteus and Klebsiella, with observations on combinations with other antibiotics and against other bacterial species.", "content": "Thirty-five strains each of Klebsiella and Proteus were tested for susceptibility to mecillinam alone and in combination with ampicillin, carbenicillin, cephalothin, and cefazolin. Antibiotics were considered to be synergistic when there was a >/=fourfold reduction in minimum inhibiting concentration of both antibiotics in the combination as compared with that of each antibiotic alone. Synergy of mecillinam with ampicillin, carbenicillin, cephalothin, and cefazolin was demonstrated against 2, 3, 7, and 8 of the 35 strains of Klebsiella and against 14, 14, 19, and 24 of the 35 strains of Proteus, respectively. Synergy against the isolates of Proteus was related to species, whereas against Klebsiella it was related to susceptibility of the isolates to mecillinam. Tests of combinations of mecillinam with other antibiotics on the same and different species indicated that synergy was related to the antibiotic, the species, and the strains of organisms tested.", "contents": "Synergy of mecillinam (FL1060) with penicillins and cephalosporins against Proteus and Klebsiella, with observations on combinations with other antibiotics and against other bacterial species. Thirty-five strains each of Klebsiella and Proteus were tested for susceptibility to mecillinam alone and in combination with ampicillin, carbenicillin, cephalothin, and cefazolin. Antibiotics were considered to be synergistic when there was a >/=fourfold reduction in minimum inhibiting concentration of both antibiotics in the combination as compared with that of each antibiotic alone. Synergy of mecillinam with ampicillin, carbenicillin, cephalothin, and cefazolin was demonstrated against 2, 3, 7, and 8 of the 35 strains of Klebsiella and against 14, 14, 19, and 24 of the 35 strains of Proteus, respectively. Synergy against the isolates of Proteus was related to species, whereas against Klebsiella it was related to susceptibility of the isolates to mecillinam. Tests of combinations of mecillinam with other antibiotics on the same and different species indicated that synergy was related to the antibiotic, the species, and the strains of organisms tested."} {"id": "PMID:1267443", "title": "Comparison of phlebitis produced by cephapirin and cephalothin.", "content": "In a single-blinded study involving 120 patients neither the incidence nor severity of phlebitis observed with cephapirin and cephalothin was significantly different.", "contents": "Comparison of phlebitis produced by cephapirin and cephalothin. In a single-blinded study involving 120 patients neither the incidence nor severity of phlebitis observed with cephapirin and cephalothin was significantly different."} {"id": "PMID:1267444", "title": "Comparative studies on the microbiological vitamin B12 assay at two laboratories.", "content": "The turbidimetric methods in routine use at two laboratories for the microbiological assay of vitamin B12 have been compared. Attempts were made to standardize some major parts of the method, i.e., assay design, test strain (Lactobacillus leichmannii), test medium, and reference standard. The laboratories used different approaches to achieve efficient assay procedures. During a 6-year period four comparative experiments were carried out. In these experiments the vitamin B12 content of five different products was determined in a series of independent assays at each laboratory. A satisfactory degree of agreement (difference less than 5%) was found for four of these products.", "contents": "Comparative studies on the microbiological vitamin B12 assay at two laboratories. The turbidimetric methods in routine use at two laboratories for the microbiological assay of vitamin B12 have been compared. Attempts were made to standardize some major parts of the method, i.e., assay design, test strain (Lactobacillus leichmannii), test medium, and reference standard. The laboratories used different approaches to achieve efficient assay procedures. During a 6-year period four comparative experiments were carried out. In these experiments the vitamin B12 content of five different products was determined in a series of independent assays at each laboratory. A satisfactory degree of agreement (difference less than 5%) was found for four of these products."} {"id": "PMID:1267445", "title": "Distribution of Bdellovibrio bacteriovorus in sewage works, river water, and sediments.", "content": "Bdellovibrio was found in all liquid phases of the sewage works examined. The predator was also found in all the river sediments and sewage-polluted river waters examined but could not be found in some unpolluted river waters. Bdellovibrio was able to multiply on the high numbers of bacteria present in the aerobic percolating filter film but could not survive in anaerobic sludge. Similarly, the predator was present in the aerobic surface layers of river sediments but not in the anaerobic bottom layers. The major source of Bdellovibrio in the polluted rivers examined were sewage works effluents, and numbers in both river water and sediment were correlated with river water quality. It was unlikely that Bdellovibrio was important in reducing numbers of other bacteria in either sewage or river sediment.", "contents": "Distribution of Bdellovibrio bacteriovorus in sewage works, river water, and sediments. Bdellovibrio was found in all liquid phases of the sewage works examined. The predator was also found in all the river sediments and sewage-polluted river waters examined but could not be found in some unpolluted river waters. Bdellovibrio was able to multiply on the high numbers of bacteria present in the aerobic percolating filter film but could not survive in anaerobic sludge. Similarly, the predator was present in the aerobic surface layers of river sediments but not in the anaerobic bottom layers. The major source of Bdellovibrio in the polluted rivers examined were sewage works effluents, and numbers in both river water and sediment were correlated with river water quality. It was unlikely that Bdellovibrio was important in reducing numbers of other bacteria in either sewage or river sediment."} {"id": "PMID:1267446", "title": "Intestinal microflora in rats: isolation and characterization of strictly anaerobic bacteria requiring long-chain fatty acids.", "content": "Three strains of strictly anaerobic bacteria, isolated from the cecal contents of rats, have strict requirements for long-chain fatty acids. The effect of exogenous fatty acids on the growth and fatty acid composition of the bacteria was examined. Biohydrogenation of linoleic acid into octadecenoic acid was observed. These observations suggest that long-chain fatty acids in the intestine are factors in controlling the localization and the population levels of indigenous bacteria in vivo in rats.", "contents": "Intestinal microflora in rats: isolation and characterization of strictly anaerobic bacteria requiring long-chain fatty acids. Three strains of strictly anaerobic bacteria, isolated from the cecal contents of rats, have strict requirements for long-chain fatty acids. The effect of exogenous fatty acids on the growth and fatty acid composition of the bacteria was examined. Biohydrogenation of linoleic acid into octadecenoic acid was observed. These observations suggest that long-chain fatty acids in the intestine are factors in controlling the localization and the population levels of indigenous bacteria in vivo in rats."} {"id": "PMID:1267447", "title": "Blockage by acetylene of nitrous oxide reduction in Pseudomonas perfectomarinus.", "content": "Suspensions of denitrifying cells of Pseudomonas perfectomarinus reduced nitrate and nitrate as expected to dinitrogen; but, in the presence of acetylene, nitrous oxide accumulated when nitrate or nitrate was reduced. When supplied at the outset in place of nitrate and nitrate, nitrous oxide was rapidly reduced to dinitrogen by cells incubated in anaerobic vessels in the absence of acetylene. In the presence of 0.01 atmospheres of acetylene, however, nitrous oxide was not reduced. Ethylene was not produced, nor did it influence the rate of nitrous oxide reduction when provided instead of acetylene. Cells exposed to 0.01 atmospheres of acetylene for as long as 400 min were able to reduce nitrous oxide after removal of acetylene at a rate comparable to that of cells not exposed to acetylene. Acetylene did not affect the production or functioning of assimilatory nitrate or nitrite reductase in axenic cultures of Enterobacter aerogenes or Trichoderma uride. While exposed to acetylene, bacteria in marine sediment slurries produced measurable quantities of nitrous oxide from glucose- or acetate-dependent reduction of added nitrate. Possible use of acetylene blockage for measurement of denitrification in unamended marine sediments is discussed.", "contents": "Blockage by acetylene of nitrous oxide reduction in Pseudomonas perfectomarinus. Suspensions of denitrifying cells of Pseudomonas perfectomarinus reduced nitrate and nitrate as expected to dinitrogen; but, in the presence of acetylene, nitrous oxide accumulated when nitrate or nitrate was reduced. When supplied at the outset in place of nitrate and nitrate, nitrous oxide was rapidly reduced to dinitrogen by cells incubated in anaerobic vessels in the absence of acetylene. In the presence of 0.01 atmospheres of acetylene, however, nitrous oxide was not reduced. Ethylene was not produced, nor did it influence the rate of nitrous oxide reduction when provided instead of acetylene. Cells exposed to 0.01 atmospheres of acetylene for as long as 400 min were able to reduce nitrous oxide after removal of acetylene at a rate comparable to that of cells not exposed to acetylene. Acetylene did not affect the production or functioning of assimilatory nitrate or nitrite reductase in axenic cultures of Enterobacter aerogenes or Trichoderma uride. While exposed to acetylene, bacteria in marine sediment slurries produced measurable quantities of nitrous oxide from glucose- or acetate-dependent reduction of added nitrate. Possible use of acetylene blockage for measurement of denitrification in unamended marine sediments is discussed."} {"id": "PMID:1267448", "title": "Oil degradation in soil.", "content": "The environmental effects of adding certain selected petroleum products to field soils at widely separated geographical locations under optimum conditions for biodegradation were studied. The locations selected for study of soil biodegradation of six oils (used crankcase oil from cars, used crankcase oil from trucks, an Arabian Heavy crude oil, a Coastal Mix crude oil, a home heating oil no. 2, and a residual fuel oil no. 6) were Marcus Hook, Pennsylvania, Tulsa, Oklahoma, and Corpus Christi, Texas. The investigative process, covering a period of 1 year at each location, was conducted in 14 fields plots (1.7 by 3.0 m) to which the oils were added in a single application at a rate of 11.9 m3/4 X 10(3) m2. One-half of the plots at each location were fertilized, and the incorporation of the oils and fertilizers was accomplished with rototillers to a depth of 10 to 15 cm. Concentrations of all oils decreased significantly at all locations. The average reduction ranged from 48.5 to 90.0% depending upon the type of oil and location. Rates of degradation did not exceed 2.4 m3/4 X 10(3) m2 per month. Compositional changes in the oil with time were investigated using silica gel fractionation, gas chromatography, and ultraviolet absorbance. With the possible exception of the two fuel oils, the compositional changes were generally in the same direction for all of the oils. The silica gel fractionation and gravimetric data on residual oils show that all classes of compounds were degraded, but the more polar type degrade more slowly. Analysis of runoff water, leachate, and soils indicated that at the concentration applied no oil less was observed from these plots via water movement. No significant movement of lead compounds added to the soils in the used crankcase oils was observed. Significant increases in hydrocarbon-utilizing microorganisms were demonstrated in all treated plots using either the pure hydrocarbon, n-hexadecane, or the applied oils as the growth substrate. These increases were usually sustained throughout the year. Significant increases in hydrocarbon-utilizing fungi were not demonstrated by the plating technique used. The concentrations of residual oils or their oxidation products were of sufficient magnitude in the treated plots, 9 months after application, to cause significant inhibition of plant growth. From the data obtained, it was not possible to determine the type of compounds causing this inhibition or their long-term environmental effects.", "contents": "Oil degradation in soil. The environmental effects of adding certain selected petroleum products to field soils at widely separated geographical locations under optimum conditions for biodegradation were studied. The locations selected for study of soil biodegradation of six oils (used crankcase oil from cars, used crankcase oil from trucks, an Arabian Heavy crude oil, a Coastal Mix crude oil, a home heating oil no. 2, and a residual fuel oil no. 6) were Marcus Hook, Pennsylvania, Tulsa, Oklahoma, and Corpus Christi, Texas. The investigative process, covering a period of 1 year at each location, was conducted in 14 fields plots (1.7 by 3.0 m) to which the oils were added in a single application at a rate of 11.9 m3/4 X 10(3) m2. One-half of the plots at each location were fertilized, and the incorporation of the oils and fertilizers was accomplished with rototillers to a depth of 10 to 15 cm. Concentrations of all oils decreased significantly at all locations. The average reduction ranged from 48.5 to 90.0% depending upon the type of oil and location. Rates of degradation did not exceed 2.4 m3/4 X 10(3) m2 per month. Compositional changes in the oil with time were investigated using silica gel fractionation, gas chromatography, and ultraviolet absorbance. With the possible exception of the two fuel oils, the compositional changes were generally in the same direction for all of the oils. The silica gel fractionation and gravimetric data on residual oils show that all classes of compounds were degraded, but the more polar type degrade more slowly. Analysis of runoff water, leachate, and soils indicated that at the concentration applied no oil less was observed from these plots via water movement. No significant movement of lead compounds added to the soils in the used crankcase oils was observed. Significant increases in hydrocarbon-utilizing microorganisms were demonstrated in all treated plots using either the pure hydrocarbon, n-hexadecane, or the applied oils as the growth substrate. These increases were usually sustained throughout the year. Significant increases in hydrocarbon-utilizing fungi were not demonstrated by the plating technique used. The concentrations of residual oils or their oxidation products were of sufficient magnitude in the treated plots, 9 months after application, to cause significant inhibition of plant growth. From the data obtained, it was not possible to determine the type of compounds causing this inhibition or their long-term environmental effects."} {"id": "PMID:1267449", "title": "Colonization of soil by Arthrobacter and Pseudomonas under varying conditions of water and nutrient availability as studied by plate counts and transmission electron microscopy.", "content": "Arthrobacter globiformis and a Pseudomonas soil isolate were incubated separately and in combination in soil that had been presterilized by autoclaving. Growth and other responses of the cells in situ in this soil were monitored by plate counts and transmission electron microscopy examinations of cell sections. During the soil incubations, some of the samples were first allowed to dry and then were remoistened with water or with a dilute or a concentrated nutrient solution. Based on plate counts and ultrastructural analysis. Arthrobacter seemed to be in a non-multiplying coccoid-rod resting state and to be virtually immune to soil drying. Addition of a dilute nutrient solution helped maintain cell ultrastructure and prevent a low level of lysing that occurred in the absence of nutrient addition. Addition of a concentrated nutrient solution brought on cell multiplication as both coccoid-rods and long rods, but the ultimate form with further incubation was the coccoid-rod. The Pseudomonas strain suffered death and ultrastructural deterioration as water became less available. It responded by cell multiplication to an equal extent when either water or dilute nutrients were added, but possibly was able to give a growth response to nutritive amendment when a concentrated nutrient addition was made. The Arthrobacter was not affected by the presence of Pseudomonas in dual culture. The Pseudomonas, however, possibly suffered a nutritive deficiency under these conditions.", "contents": "Colonization of soil by Arthrobacter and Pseudomonas under varying conditions of water and nutrient availability as studied by plate counts and transmission electron microscopy. Arthrobacter globiformis and a Pseudomonas soil isolate were incubated separately and in combination in soil that had been presterilized by autoclaving. Growth and other responses of the cells in situ in this soil were monitored by plate counts and transmission electron microscopy examinations of cell sections. During the soil incubations, some of the samples were first allowed to dry and then were remoistened with water or with a dilute or a concentrated nutrient solution. Based on plate counts and ultrastructural analysis. Arthrobacter seemed to be in a non-multiplying coccoid-rod resting state and to be virtually immune to soil drying. Addition of a dilute nutrient solution helped maintain cell ultrastructure and prevent a low level of lysing that occurred in the absence of nutrient addition. Addition of a concentrated nutrient solution brought on cell multiplication as both coccoid-rods and long rods, but the ultimate form with further incubation was the coccoid-rod. The Pseudomonas strain suffered death and ultrastructural deterioration as water became less available. It responded by cell multiplication to an equal extent when either water or dilute nutrients were added, but possibly was able to give a growth response to nutritive amendment when a concentrated nutrient addition was made. The Arthrobacter was not affected by the presence of Pseudomonas in dual culture. The Pseudomonas, however, possibly suffered a nutritive deficiency under these conditions."} {"id": "PMID:1267450", "title": "Natural protoplast Dunaliella as a source of protein.", "content": "The protein content of once-washed pellets of Dunaliella primalecta was 35 to 48%. Protein quality was good. Electron microscopy confirmed the absence of a cell wall.", "contents": "Natural protoplast Dunaliella as a source of protein. The protein content of once-washed pellets of Dunaliella primalecta was 35 to 48%. Protein quality was good. Electron microscopy confirmed the absence of a cell wall."} {"id": "PMID:1267451", "title": "Microapplicator and micropipette for inoculation of the embryonated chicken egg.", "content": "Aflatoxin G2 was used to test the speed and accuracy of the microapplicator and the micropipette. The 50% lethal dose of both assay systems was approximately the same, and 4.0 mug of G2 had an 85% lethal effect in both systems. The 50% lethal dose of the microapplicator and the micropipette was lower than that of the syringe but, of these, only the micropipette can combine the accuracy of the microapplicator and the speed of the syringe.", "contents": "Microapplicator and micropipette for inoculation of the embryonated chicken egg. Aflatoxin G2 was used to test the speed and accuracy of the microapplicator and the micropipette. The 50% lethal dose of both assay systems was approximately the same, and 4.0 mug of G2 had an 85% lethal effect in both systems. The 50% lethal dose of the microapplicator and the micropipette was lower than that of the syringe but, of these, only the micropipette can combine the accuracy of the microapplicator and the speed of the syringe."} {"id": "PMID:1267452", "title": "Epidermal activity in annular dermatophytosis.", "content": "In five patients with annular tinea corporis, the tritated thymidine labeling indexes were determined in the rim, center, and intermediate areas of the lesion and compared with normal skin. Labeling indexes at the rim were much higher than those of normal skin (mean, 4.2 times). Labeling indexes elsewhere in the lesion were not significantly different from those of normal skin. Histologic examination showed epidermal thickening in all areas of the lesion as compared with normal skin. This study suggests that there is an increased epidermal turnover at the rim of annular dermatophytosis that may be important in the pathophysiology and morphogenesis of such lesions.", "contents": "Epidermal activity in annular dermatophytosis. In five patients with annular tinea corporis, the tritated thymidine labeling indexes were determined in the rim, center, and intermediate areas of the lesion and compared with normal skin. Labeling indexes at the rim were much higher than those of normal skin (mean, 4.2 times). Labeling indexes elsewhere in the lesion were not significantly different from those of normal skin. Histologic examination showed epidermal thickening in all areas of the lesion as compared with normal skin. This study suggests that there is an increased epidermal turnover at the rim of annular dermatophytosis that may be important in the pathophysiology and morphogenesis of such lesions."} {"id": "PMID:1267453", "title": "Cornifying Darier disease--a unique variant. I. Report of a case.", "content": "A unique variant of Darier disease is described in which a patient was disabled by large, painful, cutaneous horns present on all extremities. The cornified lesions were distinguished by the presence of numerous corps ronds in the basal portion of the greatly hyperkeratotic stratum corneum, hypertrophic dermal villi containing enlarged capillaries, vacuolar dilatation of rough endoplasmic reticulum in sublacunar basal cells, unusually numerous Odland bodies in spinous cells adjacent to lacunae, and persistent attachment of tonofilaments to disrupted desmosomes. Complete separation of tonofilaments from intact desmosomes was not observed. Scanning electron microscopy revealed varied surface morphological appearances of corps ronds and of the epidermal cells covering the elongated dermal villi. The surface cells of cutaneous horns showed little tendency to desquamate.", "contents": "Cornifying Darier disease--a unique variant. I. Report of a case. A unique variant of Darier disease is described in which a patient was disabled by large, painful, cutaneous horns present on all extremities. The cornified lesions were distinguished by the presence of numerous corps ronds in the basal portion of the greatly hyperkeratotic stratum corneum, hypertrophic dermal villi containing enlarged capillaries, vacuolar dilatation of rough endoplasmic reticulum in sublacunar basal cells, unusually numerous Odland bodies in spinous cells adjacent to lacunae, and persistent attachment of tonofilaments to disrupted desmosomes. Complete separation of tonofilaments from intact desmosomes was not observed. Scanning electron microscopy revealed varied surface morphological appearances of corps ronds and of the epidermal cells covering the elongated dermal villi. The surface cells of cutaneous horns showed little tendency to desquamate."} {"id": "PMID:1267454", "title": "Cornifying Darier disease--a unique variant. II. Surgical treatment.", "content": "A case of severe cornifying Darier disease (keratosis follicularis) was successfully treated by deep dermal excision of diseased skin and subsequent dermabrasion, resulting in a remission lasting more than four years to date. Persistent loss of the papillary dermis was observed in the surgically treated, disease-free areas.", "contents": "Cornifying Darier disease--a unique variant. II. Surgical treatment. A case of severe cornifying Darier disease (keratosis follicularis) was successfully treated by deep dermal excision of diseased skin and subsequent dermabrasion, resulting in a remission lasting more than four years to date. Persistent loss of the papillary dermis was observed in the surgically treated, disease-free areas."} {"id": "PMID:1267455", "title": "Pseudofolliculitis of the legs.", "content": "A 19-year-old Iraqi girl had pseudofolliculitis of the legs. Plucking the hair was the initiating factor, and its discontinuation was followed by great improvement. To our knowledge, this is the first report of this entity at this site.", "contents": "Pseudofolliculitis of the legs. A 19-year-old Iraqi girl had pseudofolliculitis of the legs. Plucking the hair was the initiating factor, and its discontinuation was followed by great improvement. To our knowledge, this is the first report of this entity at this site."} {"id": "PMID:1267456", "title": "Cutaneous phycomycosis (mucormycosis) with fatal pulmonary dissemination.", "content": "Phycomycosis of the skin manifested as a spontaneous solitary ulcer of the leg in a patient with uremia. The infection later spread to the lungs and produced fatal pulmonary infarction. Histopathologic study of the lesions revealed broad nonseptate fungal hyphae that had invaded vascular channels, with areas of necrosis and acute inflammation. Primary cutaneous phycomycosis is rare. In the studied cases, dissemination of infection did not occur. The unusual feature of fatal pulmonary dissemination of primary cutaneous phycomycosis as observed in our patient has not been described in the leterature.", "contents": "Cutaneous phycomycosis (mucormycosis) with fatal pulmonary dissemination. Phycomycosis of the skin manifested as a spontaneous solitary ulcer of the leg in a patient with uremia. The infection later spread to the lungs and produced fatal pulmonary infarction. Histopathologic study of the lesions revealed broad nonseptate fungal hyphae that had invaded vascular channels, with areas of necrosis and acute inflammation. Primary cutaneous phycomycosis is rare. In the studied cases, dissemination of infection did not occur. The unusual feature of fatal pulmonary dissemination of primary cutaneous phycomycosis as observed in our patient has not been described in the leterature."} {"id": "PMID:1267457", "title": "Stevens-Johnson syndrome from ophthalmic sulfonamide.", "content": "A 71-year-old man, who had a history of a previous bullous drug reaction to a sulfonamide, began receiving an ophthalmic preparation that contained sulfacetamide sodium. The patient received only the ophthalmic sulfonamide, and it was used for one day, but he developed Stevens-Johnson syndrome. This is believed to be the first reported case of Stevens-Johnson syndrome caused by an ophthalmic sulfonamide. The sulfonamides are the best verified drug-trigger for erythema multiforme and Stevens-Johnson syndrome.", "contents": "Stevens-Johnson syndrome from ophthalmic sulfonamide. A 71-year-old man, who had a history of a previous bullous drug reaction to a sulfonamide, began receiving an ophthalmic preparation that contained sulfacetamide sodium. The patient received only the ophthalmic sulfonamide, and it was used for one day, but he developed Stevens-Johnson syndrome. This is believed to be the first reported case of Stevens-Johnson syndrome caused by an ophthalmic sulfonamide. The sulfonamides are the best verified drug-trigger for erythema multiforme and Stevens-Johnson syndrome."} {"id": "PMID:1267458", "title": "Linear porokeratosis with giant cornoid lamella.", "content": "A linear form of porokeratosis, with features that we believe have not been previously described, is presented. The lesions occurred in a dermatome distribution; some of them had a central mass of parakeratotic keratin, shaped like a horn, which we designated a \"giant cornoid lamella.\"", "contents": "Linear porokeratosis with giant cornoid lamella. A linear form of porokeratosis, with features that we believe have not been previously described, is presented. The lesions occurred in a dermatome distribution; some of them had a central mass of parakeratotic keratin, shaped like a horn, which we designated a \"giant cornoid lamella.\""} {"id": "PMID:1267459", "title": "Minocycline hydrochloride treatment for atypical acid-fast infection.", "content": "Atypical acid-fast infections are not infrequent in the Gulf Coastal region. The development of erythematous papules within three or four weeks after aquatic exposure deserves such consideration. Deeper tissues may also become involved. This should signal a caution when considering the use of corticosteroid injections in such a suspicious lesion. Inasmuch as hypertrophic scar formation at a site of trauma must be considered in the differential diagnosis, it is important to secure histopathologic examination prior to treatment. While a surgical approach has been required for the most part, oral administration of minocycline hydrochloride has brought about healing in the patients reported herein. This article deals with only three cases. However, response was complete and without recurrence in each. Such therapy is recommended prior to the use of more drastic procedures.", "contents": "Minocycline hydrochloride treatment for atypical acid-fast infection. Atypical acid-fast infections are not infrequent in the Gulf Coastal region. The development of erythematous papules within three or four weeks after aquatic exposure deserves such consideration. Deeper tissues may also become involved. This should signal a caution when considering the use of corticosteroid injections in such a suspicious lesion. Inasmuch as hypertrophic scar formation at a site of trauma must be considered in the differential diagnosis, it is important to secure histopathologic examination prior to treatment. While a surgical approach has been required for the most part, oral administration of minocycline hydrochloride has brought about healing in the patients reported herein. This article deals with only three cases. However, response was complete and without recurrence in each. Such therapy is recommended prior to the use of more drastic procedures."} {"id": "PMID:1267460", "title": "Apocrine gland organic hamartoma (apocrine nevus).", "content": "A patient had two fleshy, nontender masses, each partially filling an axillary vault. These tumors arose at puberty in normal-appearing axillae. The masses were accompanied by localized hyperhidrosis. Histopathological examination of the lesions showed that the reticular layer of the dermis had been replaced solely by lobular masses of unencapsulated, mature apocrine elements. These very rare tumors are best classified as apocrine gland organic hamartomas, or apocrine nevi. To our knowledge, such a case has never been reported or photographed.", "contents": "Apocrine gland organic hamartoma (apocrine nevus). A patient had two fleshy, nontender masses, each partially filling an axillary vault. These tumors arose at puberty in normal-appearing axillae. The masses were accompanied by localized hyperhidrosis. Histopathological examination of the lesions showed that the reticular layer of the dermis had been replaced solely by lobular masses of unencapsulated, mature apocrine elements. These very rare tumors are best classified as apocrine gland organic hamartomas, or apocrine nevi. To our knowledge, such a case has never been reported or photographed."} {"id": "PMID:1267461", "title": "Ulcerative colitis and the skin.", "content": "The association between ulcerative colitis and various abnormalities of the skin, especially pyoderma gangrenosum, has been accepted for many years. The underlying aberrations in either of the organ systems, as well as the basis of their association, however, remain obscure. Several large series of ulcerative colitis patients are reviewed to emphasize the important concomitant cutaneous findings, and investigations into the pathogenesis of pyoderma gangrenosum are discussed.", "contents": "Ulcerative colitis and the skin. The association between ulcerative colitis and various abnormalities of the skin, especially pyoderma gangrenosum, has been accepted for many years. The underlying aberrations in either of the organ systems, as well as the basis of their association, however, remain obscure. Several large series of ulcerative colitis patients are reviewed to emphasize the important concomitant cutaneous findings, and investigations into the pathogenesis of pyoderma gangrenosum are discussed."} {"id": "PMID:1267462", "title": "Incontinentia pigmenti. A world statistical analysis.", "content": "Incontinentia pigmenti (Bloch-Sulzberger syndrome) is an uncommon genodermatosis that usually affects female infants. I reviewed 464 references from the world literature and found 653 apparently valid reports of patients with incontinentia pigmenti. Skin manifestations were found to be somewhat more common than previously reported, and systemic manifestations were found in 79.8% of the patients.", "contents": "Incontinentia pigmenti. A world statistical analysis. Incontinentia pigmenti (Bloch-Sulzberger syndrome) is an uncommon genodermatosis that usually affects female infants. I reviewed 464 references from the world literature and found 653 apparently valid reports of patients with incontinentia pigmenti. Skin manifestations were found to be somewhat more common than previously reported, and systemic manifestations were found in 79.8% of the patients."} {"id": "PMID:1267481", "title": "Microbial degradation of the thiolcarbamate herbicide, diallate, in soils and by pure cultures of soil microorganisms.", "content": "The disappearance of the herbicide, Avadex (40% diallate), from five agricultural soils (differing in either pH, carbon content, or nitrogen content), incubated under sterile and non-sterile conditions, was followed for a period of 20 weeks. Avadex was rapidly lost from microbiologically active soils, with over 50% of the applied (2.5 ppm) dosage disappearing within four weeks; losses from sterile soils were much slower with recoveries of over 50% after 20 weeks. Incubation of soil with Avadex to which 14C-labeled diallate had been added resulted in rapid formation of 14CO2 from microbiologically active samples and only very slow 14CO2 formation from sterile samples. Substantial quantities of radioactivity were retained as unextractable residues in both sterile and non-sterile soils after senven days incubation. From these data it was concluded that the disappearance of the herbicide from non-sterile soils was mainly due to microbial degradation and to binding of diallate or its metabolites as residues to undefined soil components. Losses from sterile soils were attributed to both binding of residues and to a slow chemical degradation. Avadex degradation by pure cultures was studied using representative fungi isolated from the five soils. Of the fungi tested, Phoma eupyrena, Penicillium janthinellum, and Trichoderma harzianium coudl degrade at least 20% of the applied (2.5 ppm) herbicide after ten days incubation. Degradation of Avadex in soil cultures of T. harzianum was found to be slower than degradation in liquid nutrient cultures.", "contents": "Microbial degradation of the thiolcarbamate herbicide, diallate, in soils and by pure cultures of soil microorganisms. The disappearance of the herbicide, Avadex (40% diallate), from five agricultural soils (differing in either pH, carbon content, or nitrogen content), incubated under sterile and non-sterile conditions, was followed for a period of 20 weeks. Avadex was rapidly lost from microbiologically active soils, with over 50% of the applied (2.5 ppm) dosage disappearing within four weeks; losses from sterile soils were much slower with recoveries of over 50% after 20 weeks. Incubation of soil with Avadex to which 14C-labeled diallate had been added resulted in rapid formation of 14CO2 from microbiologically active samples and only very slow 14CO2 formation from sterile samples. Substantial quantities of radioactivity were retained as unextractable residues in both sterile and non-sterile soils after senven days incubation. From these data it was concluded that the disappearance of the herbicide from non-sterile soils was mainly due to microbial degradation and to binding of diallate or its metabolites as residues to undefined soil components. Losses from sterile soils were attributed to both binding of residues and to a slow chemical degradation. Avadex degradation by pure cultures was studied using representative fungi isolated from the five soils. Of the fungi tested, Phoma eupyrena, Penicillium janthinellum, and Trichoderma harzianium coudl degrade at least 20% of the applied (2.5 ppm) herbicide after ten days incubation. Degradation of Avadex in soil cultures of T. harzianum was found to be slower than degradation in liquid nutrient cultures."} {"id": "PMID:1267482", "title": "Comparative studies of instrumental and bioassay methods for the analysis of herbicide residues.", "content": "A study of the quantitative analysis of herbicide residues by both chemical and bioassay methods in soils is presented. Field and laboratory residue trials were carried out with a representative member of the following groups of herbicides: ureas, triazines, diphenylethers, phenoxyacetic acids, and dithiophosphates. Representative samples were taken at different time intervals, and degradation curves were established both by chemical methods and by two types of bioassay. Chemical analysis either separated active ingredient and metabolites by chromatographic techniques or compresied total residues. Bioassays were performed using either monocotyledons and dicotyledons or algae. The results obtained by chemical and bioassay analysis for the degradation rates of chlorotoluron, ametryn, 2,4-D and C 19490 showed a correlation coefficient of 0.914, indicating that the two methods gave almost identical results. Especially with the highly adsorbed urea and triazine herbicides, the uptake of biologically active material by test plants was slightly less than the solvent-extractable parent compound plus its metabolities, and so the absolute level of residues obtained by bioassay was lower. In the case of fluorodifen, the correlation between the methods was not established. The bioassay showed higher residues and slower degradation than chemical analysis. Various factors which could explain this anomalous result are discussed.", "contents": "Comparative studies of instrumental and bioassay methods for the analysis of herbicide residues. A study of the quantitative analysis of herbicide residues by both chemical and bioassay methods in soils is presented. Field and laboratory residue trials were carried out with a representative member of the following groups of herbicides: ureas, triazines, diphenylethers, phenoxyacetic acids, and dithiophosphates. Representative samples were taken at different time intervals, and degradation curves were established both by chemical methods and by two types of bioassay. Chemical analysis either separated active ingredient and metabolites by chromatographic techniques or compresied total residues. Bioassays were performed using either monocotyledons and dicotyledons or algae. The results obtained by chemical and bioassay analysis for the degradation rates of chlorotoluron, ametryn, 2,4-D and C 19490 showed a correlation coefficient of 0.914, indicating that the two methods gave almost identical results. Especially with the highly adsorbed urea and triazine herbicides, the uptake of biologically active material by test plants was slightly less than the solvent-extractable parent compound plus its metabolities, and so the absolute level of residues obtained by bioassay was lower. In the case of fluorodifen, the correlation between the methods was not established. The bioassay showed higher residues and slower degradation than chemical analysis. Various factors which could explain this anomalous result are discussed."} {"id": "PMID:1267483", "title": "Blue crab mortality: interaction of temperature and DDT residues.", "content": "Serial observations of DDT-contaminated and uncontaminated salt marshes in the norther Gulf of Mexico were made in November and December, 1973. Blue crab (Callinectes sapidus) mortalities observed in the DDT-contaminated marsh during this period were correlated with reduced daily temperature minima. Gas chromatographic analysis of hepatopancreas and swimmeret muscle tissue of dead and dying crabs revealed total DDT residue concentrations as high as 39.0 ppm and 1.43 ppm, respectively. It is suggested that the DDT body burdens and reduced temperatures interact to produce acutely toxic effects. Several physiological and behavioral mechanisms are proposed.", "contents": "Blue crab mortality: interaction of temperature and DDT residues. Serial observations of DDT-contaminated and uncontaminated salt marshes in the norther Gulf of Mexico were made in November and December, 1973. Blue crab (Callinectes sapidus) mortalities observed in the DDT-contaminated marsh during this period were correlated with reduced daily temperature minima. Gas chromatographic analysis of hepatopancreas and swimmeret muscle tissue of dead and dying crabs revealed total DDT residue concentrations as high as 39.0 ppm and 1.43 ppm, respectively. It is suggested that the DDT body burdens and reduced temperatures interact to produce acutely toxic effects. Several physiological and behavioral mechanisms are proposed."} {"id": "PMID:1267484", "title": "Translocation, distribution and metabolism of triforine in plants.", "content": "After short-ter root-treatment of plants with 3H-triforine (labelled in the piperazine ring) or 14C-triforine (labelled in the side chain), the label was translocated primarily to the leaves present at the time of treatment, without any redistribution of the label taking place after termination of the treatment. Autoradiography showed the radioactivity to be very evenly distributed over the leaf blades, without any appreciable accumulation in leaf margins. In infected leaves, however, there was a tendency for increased accumulation at the infection sites. In dilute aqueous solution triforine was decomposed rather rapidly, the chemical half-life being three days only. From these solutions several non-fungitoxic degradtion products have been isolated and their chemical structures determined. In plants, decomposition of triforine was considerably slower than in aqueous solutions, the half-life of the compound varying depending on plant species. In plants, at least four conversion products could be demonstrated, one of which is piperazine. Whether the other three compounds are identical with or structurally related to the breakdown products found in aqueous solution is not yet known. Its low persistence and low animal toxicity suggest that triforine does not offer serious hazards to the environment.", "contents": "Translocation, distribution and metabolism of triforine in plants. After short-ter root-treatment of plants with 3H-triforine (labelled in the piperazine ring) or 14C-triforine (labelled in the side chain), the label was translocated primarily to the leaves present at the time of treatment, without any redistribution of the label taking place after termination of the treatment. Autoradiography showed the radioactivity to be very evenly distributed over the leaf blades, without any appreciable accumulation in leaf margins. In infected leaves, however, there was a tendency for increased accumulation at the infection sites. In dilute aqueous solution triforine was decomposed rather rapidly, the chemical half-life being three days only. From these solutions several non-fungitoxic degradtion products have been isolated and their chemical structures determined. In plants, decomposition of triforine was considerably slower than in aqueous solutions, the half-life of the compound varying depending on plant species. In plants, at least four conversion products could be demonstrated, one of which is piperazine. Whether the other three compounds are identical with or structurally related to the breakdown products found in aqueous solution is not yet known. Its low persistence and low animal toxicity suggest that triforine does not offer serious hazards to the environment."} {"id": "PMID:1267485", "title": "Thermal effects on the accumulation of arsenic in green sunfish, Lepomis cyanellus.", "content": "The pattern of arsenic concentration in several tissues of Lepomis cyanellus was measured (by neutron activation analysis) as a function of exposure time at 10 degrees, 20 degrees, and 30 degrees C and 0, 30, 60 ppm of arsenic as sodium arsenate. Individual variability of aresenic uptake did not override trends of greater uptake with increasing exposure time, temperature, and arsenic concentration. The mean temperature coefficient of 4.5 for arsenic uptake in livers was higher than O'Hara's (1968) metabolic figures of 1.6 to 3.0 for Lepomis species. The biological half-life of arsenic in liver and gut of live specimens exposed to 30 and 60 ppm of arsenic at 10 degrees C was about one week. Percentage survival decreased and mean arsenic uptake increased slightly as temperature and arsenic concentration increased.", "contents": "Thermal effects on the accumulation of arsenic in green sunfish, Lepomis cyanellus. The pattern of arsenic concentration in several tissues of Lepomis cyanellus was measured (by neutron activation analysis) as a function of exposure time at 10 degrees, 20 degrees, and 30 degrees C and 0, 30, 60 ppm of arsenic as sodium arsenate. Individual variability of aresenic uptake did not override trends of greater uptake with increasing exposure time, temperature, and arsenic concentration. The mean temperature coefficient of 4.5 for arsenic uptake in livers was higher than O'Hara's (1968) metabolic figures of 1.6 to 3.0 for Lepomis species. The biological half-life of arsenic in liver and gut of live specimens exposed to 30 and 60 ppm of arsenic at 10 degrees C was about one week. Percentage survival decreased and mean arsenic uptake increased slightly as temperature and arsenic concentration increased."} {"id": "PMID:1267486", "title": "Residue uptake and depletion measurements of dietary oxadiazon in mammalian and avian species.", "content": "The herbicide oxadiazon, 2-(tert-butyl)-4-(2,4-dichloro-5-isopropyloxy-phenyl)-delta 2-1,3,4-oxadiazoline 5-one, was fed in a total diet at three dosage levels to groups of dairy cows (0.5, 2.5, and 25 ppm) and to groups of male and laying female quail (20, 80, and 160 ppm) for 28 days. Control animals received basal diet rations. No residue (less than 5 ppb) was detected in milk or cream after three days withdrawal from fortified feed. The maximum plateau reached in milk was 83.8 ppb at the highest dosage fed. Tissues of cows sacrificed on the 12th day of withdrawal showed no residue (less than 20 ppb). Birds were sacrified at weekly intervals during acclimation, intake, and withdrawal periods. Eggs were collected at the same intervals. Tissues were free of oxadiazon residue (less than 40 ppb) within two to seven days of returning the quail to the basal ration, and the eggs were residue-free within seven to fourteen days. The maximum residue found in adipose tissue of quail and their fresh eggs was 3100 ppb and 5400 ppb, respectively at the greatly exaggerated dosage of 160 ppm in the diet. A comprehensive analytical methodology, including liquid-liquid partition, absorption chromatography and electron-capture gas chromatography will be discussed.", "contents": "Residue uptake and depletion measurements of dietary oxadiazon in mammalian and avian species. The herbicide oxadiazon, 2-(tert-butyl)-4-(2,4-dichloro-5-isopropyloxy-phenyl)-delta 2-1,3,4-oxadiazoline 5-one, was fed in a total diet at three dosage levels to groups of dairy cows (0.5, 2.5, and 25 ppm) and to groups of male and laying female quail (20, 80, and 160 ppm) for 28 days. Control animals received basal diet rations. No residue (less than 5 ppb) was detected in milk or cream after three days withdrawal from fortified feed. The maximum plateau reached in milk was 83.8 ppb at the highest dosage fed. Tissues of cows sacrificed on the 12th day of withdrawal showed no residue (less than 20 ppb). Birds were sacrified at weekly intervals during acclimation, intake, and withdrawal periods. Eggs were collected at the same intervals. Tissues were free of oxadiazon residue (less than 40 ppb) within two to seven days of returning the quail to the basal ration, and the eggs were residue-free within seven to fourteen days. The maximum residue found in adipose tissue of quail and their fresh eggs was 3100 ppb and 5400 ppb, respectively at the greatly exaggerated dosage of 160 ppm in the diet. A comprehensive analytical methodology, including liquid-liquid partition, absorption chromatography and electron-capture gas chromatography will be discussed."} {"id": "PMID:1267487", "title": "Effects of the herbicide 2,4-DB and fungicide captan on reactions of mitochondria and chloroplasts.", "content": "The effects of the herbicide 4(2,4-dichlorophenoxy)butyric acid (2,4-DB) and fungicide N-(trichloromethyltio)-4-cyclohexene-1,2-dicarboximide (captan) on electron transport processes of mitochondria and chloroplasts have been investigated. Chloroplasts, isolated from spinach leaves (Spinacia oleracea L.), were treated with pesticide prior to the addition of electron acceptor and ADP. White potato (Solanum tuberosum L.) mitochondria were either incubated with pesticide before the addition of substrate, or they were treated with pesticide after the addition of substrate and ADP. Captan inhibited oxidation of malate by mitochondria and acted as an uncoupler. With succinate as sunstrate captan was found to stimulate state 4 respiration, as substrate captan was found to stimulate state 4 respiration, with the loss of coupled phosphorylation only at higher concentrations of fungicide. The herbicide 2,4-DB appeared to be 5 to 10 times less effective than captain. Both compounds inhibited phosphrylation-coupled succinate oxidation at higher concentrations and malate-coupled phosphorylation at lower concentrations. They acted as inhibitors of NADH-cytochrome c reductase. Both pesticides inhibited noncyclic electron transport in chloroplasts. The rate of ferricyanide reduction in the presence and absence of phosphorylating agents was reduced, and although the rate of ATP generation was reduced also, the P/2e ratio was not changed much under the influence of pesticides.", "contents": "Effects of the herbicide 2,4-DB and fungicide captan on reactions of mitochondria and chloroplasts. The effects of the herbicide 4(2,4-dichlorophenoxy)butyric acid (2,4-DB) and fungicide N-(trichloromethyltio)-4-cyclohexene-1,2-dicarboximide (captan) on electron transport processes of mitochondria and chloroplasts have been investigated. Chloroplasts, isolated from spinach leaves (Spinacia oleracea L.), were treated with pesticide prior to the addition of electron acceptor and ADP. White potato (Solanum tuberosum L.) mitochondria were either incubated with pesticide before the addition of substrate, or they were treated with pesticide after the addition of substrate and ADP. Captan inhibited oxidation of malate by mitochondria and acted as an uncoupler. With succinate as sunstrate captan was found to stimulate state 4 respiration, as substrate captan was found to stimulate state 4 respiration, with the loss of coupled phosphorylation only at higher concentrations of fungicide. The herbicide 2,4-DB appeared to be 5 to 10 times less effective than captain. Both compounds inhibited phosphrylation-coupled succinate oxidation at higher concentrations and malate-coupled phosphorylation at lower concentrations. They acted as inhibitors of NADH-cytochrome c reductase. Both pesticides inhibited noncyclic electron transport in chloroplasts. The rate of ferricyanide reduction in the presence and absence of phosphorylating agents was reduced, and although the rate of ATP generation was reduced also, the P/2e ratio was not changed much under the influence of pesticides."} {"id": "PMID:1267488", "title": "Metabolism of ethephon (2-chloroethylphosphonic acid) and related compounds in Hevea brasiliensis.", "content": "Ethephon (I) is used commercially to prolong the flow of latex from the rubber tree after tapping (Yield stimulation). The compound is applied to the bark in the region of the tapping cut and the effect on latex flow is due to the ethylene released by chemical decomposition, since gaseous ethylene itself is also a very effective stimulant. When 14C-I is applied to the bark of a young Hevea seedling, it is absorbed into the plant by processes which appear to be largely non-metabolic. Ethylene formation commences immediately at the site of application, and the gas is quickly translocated throughout the plant. Translocation of I to all parts of the plant also occurs and the accumulation of 14C in the bark above the zone of application is greater than that below. Chromatographic analysis has shown that compounds other than I remain in the plant tissue. Experiments using 14C-I have shown that detached leaves are able to convert a considerable proportion of the compound to at least twelve non-volatile acid products. One of these is a conjugate of I with an unidentified material. A major component of the products is 2-hydroxyethylphosphonic acid (II), which is itself converted to a number of compounds in leaves. The application of I to bark from mature Hevea, results in the formation of a single substance which is also a conjugate of I. Neither I nor II is effective in inducing the formation of ethylene from endogenous precursors in vegetative Hevea tissue. Ethylene is poorly metabolized by Hevea leaves and the evidence available indicates that it is unlikely that any of the compounds produced from I are metabolites of ethylene.", "contents": "Metabolism of ethephon (2-chloroethylphosphonic acid) and related compounds in Hevea brasiliensis. Ethephon (I) is used commercially to prolong the flow of latex from the rubber tree after tapping (Yield stimulation). The compound is applied to the bark in the region of the tapping cut and the effect on latex flow is due to the ethylene released by chemical decomposition, since gaseous ethylene itself is also a very effective stimulant. When 14C-I is applied to the bark of a young Hevea seedling, it is absorbed into the plant by processes which appear to be largely non-metabolic. Ethylene formation commences immediately at the site of application, and the gas is quickly translocated throughout the plant. Translocation of I to all parts of the plant also occurs and the accumulation of 14C in the bark above the zone of application is greater than that below. Chromatographic analysis has shown that compounds other than I remain in the plant tissue. Experiments using 14C-I have shown that detached leaves are able to convert a considerable proportion of the compound to at least twelve non-volatile acid products. One of these is a conjugate of I with an unidentified material. A major component of the products is 2-hydroxyethylphosphonic acid (II), which is itself converted to a number of compounds in leaves. The application of I to bark from mature Hevea, results in the formation of a single substance which is also a conjugate of I. Neither I nor II is effective in inducing the formation of ethylene from endogenous precursors in vegetative Hevea tissue. Ethylene is poorly metabolized by Hevea leaves and the evidence available indicates that it is unlikely that any of the compounds produced from I are metabolites of ethylene."} {"id": "PMID:1267489", "title": "Human subject experiments to estimate reentry periods for monocrotophos-treated tobacco.", "content": "Thirteen to fifteen human volunteers worked for eight-hr periods in tobacco fields treated 96, 72, and 48 hr previously with monocrotophos (3-hydroxy-N-methyl-cis-crotonamide dimethyl phosphate). At the 48-hr reentry period, during which time no rainfall occurred, both post-exposure plasma and red blood cell cholinesterase levels of the worker group were depressed from pre-exposure levels although the decline was less than 9% in both cases. Rainfall in excess of one inch fell during the 96- and 72-hr reentry intervals, and no important change in cholinesterase levels was noted. Experiments with mice were in general agreement with the human tests. Dimethyl phosphoric acid in urine of the worker group collected prior to, and three hr after, exposure was unchanged in all cases. Rain appeared to have markedly reduced dislodgable residues.", "contents": "Human subject experiments to estimate reentry periods for monocrotophos-treated tobacco. Thirteen to fifteen human volunteers worked for eight-hr periods in tobacco fields treated 96, 72, and 48 hr previously with monocrotophos (3-hydroxy-N-methyl-cis-crotonamide dimethyl phosphate). At the 48-hr reentry period, during which time no rainfall occurred, both post-exposure plasma and red blood cell cholinesterase levels of the worker group were depressed from pre-exposure levels although the decline was less than 9% in both cases. Rainfall in excess of one inch fell during the 96- and 72-hr reentry intervals, and no important change in cholinesterase levels was noted. Experiments with mice were in general agreement with the human tests. Dimethyl phosphoric acid in urine of the worker group collected prior to, and three hr after, exposure was unchanged in all cases. Rain appeared to have markedly reduced dislodgable residues."} {"id": "PMID:1267490", "title": "Carcinoma of the ampulla of Vater: Review of 38 cases with emphasis on treatment and prognostic factors.", "content": "Thirty-eight cases of carcinoma of the ampulla of Vater are presented. The diagnosis has been confirmed at laparatomy in all patients. Three operations were done, a pancreaticoduodenal resection in 23 patients, a biliary-enteric bypass in 7 patients and a biliary-enteric bypass plus excision of tumor in 8 patients. The operative mortality was 8% following resection, 14% following bypass plus excision of the ampulla and 13% following biliary-enteric bypass. Five patients survived 5 or more years. The longest survivors have followed pancreaticoduodenal resections (131 and 216 months). The level of bilirubin or presence of pain did not correlate with prognosis. Prognosis was better in the absence of nodal metastases, and in the presence of papillary tumors.", "contents": "Carcinoma of the ampulla of Vater: Review of 38 cases with emphasis on treatment and prognostic factors. Thirty-eight cases of carcinoma of the ampulla of Vater are presented. The diagnosis has been confirmed at laparatomy in all patients. Three operations were done, a pancreaticoduodenal resection in 23 patients, a biliary-enteric bypass in 7 patients and a biliary-enteric bypass plus excision of tumor in 8 patients. The operative mortality was 8% following resection, 14% following bypass plus excision of the ampulla and 13% following biliary-enteric bypass. Five patients survived 5 or more years. The longest survivors have followed pancreaticoduodenal resections (131 and 216 months). The level of bilirubin or presence of pain did not correlate with prognosis. Prognosis was better in the absence of nodal metastases, and in the presence of papillary tumors."} {"id": "PMID:1267491", "title": "Staphylococci in community-acquired infections: Increased resistance to penicillin.", "content": "One hundred patients with community-acquired staphylococcal infections of the skin and soft tissues were treated in the Emergency Ward of Cleveland Metropolitan General Hospital from June to October of 1974. Each staphylococcal infection was considered community-acquired if, within two weeks prior to being treated for the first time, the patient had not received antibiotics, had not been hospitalized, and had not been in contact with other recently hospitalized persons. Of 100 community-acquired staphylococcal infections, 85 were resistant to penicillin. Almost no resistance to other tested antibiotics was observed. Unless indicated otherwise by bacteriologic testing, penicillin is a poor drug of choice in those skin and soft tissue infections suspected of harboring staphylococci.", "contents": "Staphylococci in community-acquired infections: Increased resistance to penicillin. One hundred patients with community-acquired staphylococcal infections of the skin and soft tissues were treated in the Emergency Ward of Cleveland Metropolitan General Hospital from June to October of 1974. Each staphylococcal infection was considered community-acquired if, within two weeks prior to being treated for the first time, the patient had not received antibiotics, had not been hospitalized, and had not been in contact with other recently hospitalized persons. Of 100 community-acquired staphylococcal infections, 85 were resistant to penicillin. Almost no resistance to other tested antibiotics was observed. Unless indicated otherwise by bacteriologic testing, penicillin is a poor drug of choice in those skin and soft tissue infections suspected of harboring staphylococci."} {"id": "PMID:1267492", "title": "In vitro penetration of topical antiseptics through eschar of burn patients.", "content": "The ability of topical antiseptics to penetrate eschar of burn patients was determined by the agar diffusion technique. Gentamicin sulfate, mafenide acetate, nitrofurazone, povidone-iodine, silver nitrate, and silver sulfadiazine were tested against clinical isolates of Candida albicans, Staphylococcus, Streptococcus, and gram-negative bacilli including Pseudomonas aeruginosa. In practically all instances, the diameters of the zones of inhibition observed using eschar were comparable to those obtained with filter-paper discs. This finding showed that the antimicrobial agents could penetrate eschar and retain their effectiveness after penetration.", "contents": "In vitro penetration of topical antiseptics through eschar of burn patients. The ability of topical antiseptics to penetrate eschar of burn patients was determined by the agar diffusion technique. Gentamicin sulfate, mafenide acetate, nitrofurazone, povidone-iodine, silver nitrate, and silver sulfadiazine were tested against clinical isolates of Candida albicans, Staphylococcus, Streptococcus, and gram-negative bacilli including Pseudomonas aeruginosa. In practically all instances, the diameters of the zones of inhibition observed using eschar were comparable to those obtained with filter-paper discs. This finding showed that the antimicrobial agents could penetrate eschar and retain their effectiveness after penetration."} {"id": "PMID:1267493", "title": "The effect of acute popliteal venous interruption.", "content": "Popliteal vascular trauma continues to be associated with a relatively high morbidity rate when compared to other major vascular injuries in extremities. There is continuing controversy regarding the management of popliteal venous injuries. The advocates of ligation of injured veins have postulated that there is an increased incidence in thrombophlebitis and pulmonary embolism associated with attempted venous repair. There is a paucity of valid statistics supporting either side of this controversy. Clinical experience documented in the Vietnam Vascular Registry and experimental work at Walter Reed Army Institute of Research have supported our more aggressive approach for venous repair. This study evaluates the management of 110 injured popliteal veins without associated popliteal arterial trauma. Nearly an equal number were ligated and repaired. Thrombophlebitis and pulmonary embolism were not significant complications in this series. The only pulmonary embolus occurred after ligation of an injured popliteal vein. However, there was a significant increase in edema of the involved extremity following ligation, 50.9% compared to 13.2% after repair.", "contents": "The effect of acute popliteal venous interruption. Popliteal vascular trauma continues to be associated with a relatively high morbidity rate when compared to other major vascular injuries in extremities. There is continuing controversy regarding the management of popliteal venous injuries. The advocates of ligation of injured veins have postulated that there is an increased incidence in thrombophlebitis and pulmonary embolism associated with attempted venous repair. There is a paucity of valid statistics supporting either side of this controversy. Clinical experience documented in the Vietnam Vascular Registry and experimental work at Walter Reed Army Institute of Research have supported our more aggressive approach for venous repair. This study evaluates the management of 110 injured popliteal veins without associated popliteal arterial trauma. Nearly an equal number were ligated and repaired. Thrombophlebitis and pulmonary embolism were not significant complications in this series. The only pulmonary embolus occurred after ligation of an injured popliteal vein. However, there was a significant increase in edema of the involved extremity following ligation, 50.9% compared to 13.2% after repair."} {"id": "PMID:1267494", "title": "Penetrating cardiac wounds: A comparison of different therapeutic methods.", "content": "The management of penetrating wounds of the heart has been controversial. During the last 10 years we have used 3 different therapeutic approaches for the treatment of these wounds and the obtained results comprise this report. From 1964 to 1974 we treated 102 patients, four of whom expired immediately after their arrival to the clinic. The remaining 98 patients were divided into five groups according to their clinical presentation and treatment. Group I, 17 patients (14 with stab and 3 with bullet wound) seen with cardiac tamponade from 1964 to 1967 were treated first with pericardiocentesis and then were operated upon if pericardiocentesis yielded no results or if cardiac tamponade recurred. Fourteen patients recovered and three died, with an overall mortality of 17.5% Group II, 34 patients (23 with stab and 11 with bullet wound) were seen with cardiac tamponade from 1968 to 1971. The patients with stab wound were managed the same as group I patients and those with bullet wound were operated upon immediately. Twenty-nine recovered and 5 died, with an overall mortality of 14.7%. Group III, 20 patients (12 with stab and 8 with bullet wound) were seen with cardiac tamponade from 1972 to 1974. All of them were operated upon immediately and pericardiocentesis was used in this group only to provide time for a safe operation. Nineteen recovered and one died, with an overall mortality of 5%. Group IV, 20 patients (5 with stab and 15 with bullet wound) with massive bleeding, were operated upon immediately. Ten (4 out of the 5 with stab and 6 out of the 15 with bullet wound) recovered, with a mortality rate of 50%. Group V, seven patients were seen throughout the study period without bleeding or cardiac tamponade. Some of them were operated upon electively and others are being followed and all have done well. This study suggests (1) that patients with penetrating wound of the heart and cardiac tamponade or bleeding will derive better results if they are operated upon as soon as possible and if pericardiocentesis is used to provide time for a safe operation and (2) that those with other manifestations should be evaluated and if their lesion is significant, they should be operated upon electively.", "contents": "Penetrating cardiac wounds: A comparison of different therapeutic methods. The management of penetrating wounds of the heart has been controversial. During the last 10 years we have used 3 different therapeutic approaches for the treatment of these wounds and the obtained results comprise this report. From 1964 to 1974 we treated 102 patients, four of whom expired immediately after their arrival to the clinic. The remaining 98 patients were divided into five groups according to their clinical presentation and treatment. Group I, 17 patients (14 with stab and 3 with bullet wound) seen with cardiac tamponade from 1964 to 1967 were treated first with pericardiocentesis and then were operated upon if pericardiocentesis yielded no results or if cardiac tamponade recurred. Fourteen patients recovered and three died, with an overall mortality of 17.5% Group II, 34 patients (23 with stab and 11 with bullet wound) were seen with cardiac tamponade from 1968 to 1971. The patients with stab wound were managed the same as group I patients and those with bullet wound were operated upon immediately. Twenty-nine recovered and 5 died, with an overall mortality of 14.7%. Group III, 20 patients (12 with stab and 8 with bullet wound) were seen with cardiac tamponade from 1972 to 1974. All of them were operated upon immediately and pericardiocentesis was used in this group only to provide time for a safe operation. Nineteen recovered and one died, with an overall mortality of 5%. Group IV, 20 patients (5 with stab and 15 with bullet wound) with massive bleeding, were operated upon immediately. Ten (4 out of the 5 with stab and 6 out of the 15 with bullet wound) recovered, with a mortality rate of 50%. Group V, seven patients were seen throughout the study period without bleeding or cardiac tamponade. Some of them were operated upon electively and others are being followed and all have done well. This study suggests (1) that patients with penetrating wound of the heart and cardiac tamponade or bleeding will derive better results if they are operated upon as soon as possible and if pericardiocentesis is used to provide time for a safe operation and (2) that those with other manifestations should be evaluated and if their lesion is significant, they should be operated upon electively."} {"id": "PMID:1267495", "title": "L-dopa in hepatic coma.", "content": "The use of L-Dopa in hepatic coma has been the subject of numerous reports since 1970. The following represents our experience with a rather heterogenous group of patients treated at the Massachusetts General Hospital over the past 4 years. Thirty-five patients with severe liver disease, a mean age of 53 +/- 3.5 years, including nutritional cirrhosis with acute coma and acute hepatitis were treated. Four patients were judged grade III, 31 patients grade IV. All patients had previously been treated with protein restriction, orally administered non-absorbable antibiotics, fluid and electrolytes, and in some cases, steroids. L-Dopa was given orally in 21 patients, and as a retention enema in 14. Thirteen of the 35 patients did not respond to therapy. Seventeen responded, but did not survive, and 5 patients responded and survived. There was no difference between any of the groups as far as dosage of L-Dopa and clinical features. The one striking finding as the differences between groups was the time of initiation of L-Dopa therapy. In Group I, the survivors, therapy was started within 1.4 +/- 0.8 days after the onset of coma. In Group II, there was an initiation of therapy at 6.7 +/- 1.6 days, and in the non-responders 9.5 +/- 1.6 days. These differences are highly significant. The results suggest that coma may pass from a reversible to an irreversible stage, and that L-Dopa therapy initiated early in the course of hepatic coma, may be of some benefit.", "contents": "L-dopa in hepatic coma. The use of L-Dopa in hepatic coma has been the subject of numerous reports since 1970. The following represents our experience with a rather heterogenous group of patients treated at the Massachusetts General Hospital over the past 4 years. Thirty-five patients with severe liver disease, a mean age of 53 +/- 3.5 years, including nutritional cirrhosis with acute coma and acute hepatitis were treated. Four patients were judged grade III, 31 patients grade IV. All patients had previously been treated with protein restriction, orally administered non-absorbable antibiotics, fluid and electrolytes, and in some cases, steroids. L-Dopa was given orally in 21 patients, and as a retention enema in 14. Thirteen of the 35 patients did not respond to therapy. Seventeen responded, but did not survive, and 5 patients responded and survived. There was no difference between any of the groups as far as dosage of L-Dopa and clinical features. The one striking finding as the differences between groups was the time of initiation of L-Dopa therapy. In Group I, the survivors, therapy was started within 1.4 +/- 0.8 days after the onset of coma. In Group II, there was an initiation of therapy at 6.7 +/- 1.6 days, and in the non-responders 9.5 +/- 1.6 days. These differences are highly significant. The results suggest that coma may pass from a reversible to an irreversible stage, and that L-Dopa therapy initiated early in the course of hepatic coma, may be of some benefit."} {"id": "PMID:1267496", "title": "Boerhaave's syndrome: The importance of early diagnosis and treatment.", "content": "Boerhaave's syndrome, spontaneous esophageal rupture, is associated with a 70% survival with surgical intervention. Mortality and morbidity are increased in direct proportion to the time between diagnosis and appropriate surgical intervention. Sepsis, hypovolemia and shock are the predominant causes of morbidity and mortality in Boerhaave's syndrome. Two cases of Boerhaave's syndrome are presented which were diagnosed rapidly, and were managed surgically, resulting in survival of the patients. A review of the literature is also presented with emphasis on the clinical and roentgenologic methods of diagnosis of spontaneous esophageal rupture. Particular attention is given to the fact that early diagnosis and treatment will unquestionably reduce the morbidity of this syndrome.", "contents": "Boerhaave's syndrome: The importance of early diagnosis and treatment. Boerhaave's syndrome, spontaneous esophageal rupture, is associated with a 70% survival with surgical intervention. Mortality and morbidity are increased in direct proportion to the time between diagnosis and appropriate surgical intervention. Sepsis, hypovolemia and shock are the predominant causes of morbidity and mortality in Boerhaave's syndrome. Two cases of Boerhaave's syndrome are presented which were diagnosed rapidly, and were managed surgically, resulting in survival of the patients. A review of the literature is also presented with emphasis on the clinical and roentgenologic methods of diagnosis of spontaneous esophageal rupture. Particular attention is given to the fact that early diagnosis and treatment will unquestionably reduce the morbidity of this syndrome."} {"id": "PMID:1267497", "title": "Breast cancer presenting as an axillary mass.", "content": "Experience with breast cancer presenting as an axillary mass in 42 patients has been reviewed according to initial clinical findings, treatment and survival. In the absence of an obvious inflammatory lesion, an axillary node may prove to be the first sign of breast cancer. It has been demonstrated that such a node should be biopsied and if positive for adenocarcinoma, a radical mastectomy performed presuming other primary sites have been ruled out. The survival rate after surgery in this group of patients is better than in those who present with a palpable breast mass and have axillary metastases.", "contents": "Breast cancer presenting as an axillary mass. Experience with breast cancer presenting as an axillary mass in 42 patients has been reviewed according to initial clinical findings, treatment and survival. In the absence of an obvious inflammatory lesion, an axillary node may prove to be the first sign of breast cancer. It has been demonstrated that such a node should be biopsied and if positive for adenocarcinoma, a radical mastectomy performed presuming other primary sites have been ruled out. The survival rate after surgery in this group of patients is better than in those who present with a palpable breast mass and have axillary metastases."} {"id": "PMID:1267498", "title": "Postoperative deep vein thrombosis in the lower extremity amputee: A prospective study with Doppler ultrasound.", "content": "The incidence of postoperative venous thrombosis and pulmonary embolism was assessed in 87 patients undergoing 96 major lower extremity amputations for ischemia. Prospective surveillance for deep leg vein thrombosis was carried out by Doppler ultrasound in 35 patients. There was no instance of major leg vein thrombosis and only one episode of a small non-fatal pulmonary embolus in a patient suffering trauma to the amputation stump after discharge from the hospital. This study suggests that clinically significant venous thromboembolism following current techniques of lower extremity amputation is not as common as previously reported. Doppler ultrasound is the most suitable technique for surveillance of venous thrombosis in these patients.", "contents": "Postoperative deep vein thrombosis in the lower extremity amputee: A prospective study with Doppler ultrasound. The incidence of postoperative venous thrombosis and pulmonary embolism was assessed in 87 patients undergoing 96 major lower extremity amputations for ischemia. Prospective surveillance for deep leg vein thrombosis was carried out by Doppler ultrasound in 35 patients. There was no instance of major leg vein thrombosis and only one episode of a small non-fatal pulmonary embolus in a patient suffering trauma to the amputation stump after discharge from the hospital. This study suggests that clinically significant venous thromboembolism following current techniques of lower extremity amputation is not as common as previously reported. Doppler ultrasound is the most suitable technique for surveillance of venous thrombosis in these patients."} {"id": "PMID:1267499", "title": "Spontaneous rupture of the common bile duct.", "content": "Spontaneous rupture of the common bile duct is an extremely rare condition. Only 11 cases have been reported in the world literature. An unusual case of this complication is reported and the possible etiology and pathogenesis are discussed.", "contents": "Spontaneous rupture of the common bile duct. Spontaneous rupture of the common bile duct is an extremely rare condition. Only 11 cases have been reported in the world literature. An unusual case of this complication is reported and the possible etiology and pathogenesis are discussed."} {"id": "PMID:1267500", "title": "Long-term results of brachial thrombectomy following cardiac catheterization.", "content": "The late results of brachial thrombectomy following cardiac catheterization were evaluated in 20 patients. All patients had a radial pulse present and no symptoms or signs of ischemia of the hand at the time of discharge from the hospital. Late evaluation of these 20 patients revealed 8 in whom the long-term results were classified as failure of the thrombectomy. Four of these had intermittent claudication of the involved arm and hand. None had any tissue loss and four had no symptoms referable to the failed thrombectomy. The one patient who refused surgery had claudication of the affected arm. The mean period of followup was 20.8 months. The rate of failed thrombectomies was twice as high in females than in males. Prolonged time of cardiac catheterization (over 4 hours), delay in diagnosis of more than 24 hours, and omitting the use of systemic heparinization at the time of diagnosis are three factors that appear to increase the likelihood of late failures.", "contents": "Long-term results of brachial thrombectomy following cardiac catheterization. The late results of brachial thrombectomy following cardiac catheterization were evaluated in 20 patients. All patients had a radial pulse present and no symptoms or signs of ischemia of the hand at the time of discharge from the hospital. Late evaluation of these 20 patients revealed 8 in whom the long-term results were classified as failure of the thrombectomy. Four of these had intermittent claudication of the involved arm and hand. None had any tissue loss and four had no symptoms referable to the failed thrombectomy. The one patient who refused surgery had claudication of the affected arm. The mean period of followup was 20.8 months. The rate of failed thrombectomies was twice as high in females than in males. Prolonged time of cardiac catheterization (over 4 hours), delay in diagnosis of more than 24 hours, and omitting the use of systemic heparinization at the time of diagnosis are three factors that appear to increase the likelihood of late failures."} {"id": "PMID:1267501", "title": "Portal diversion for portal hypertension in early childhood.", "content": "Twenty-three children under 6 years of age with portal hypertention were treated by portal diversion. Fourteen had cavernomatous transformation of the portal vein and 9 had an intrahepatic block due to cirrhosis (8) or congenital hepatic fibrosis (1). Portal-systemic shunts were central splenorenal in 20 patients, side-to-side portacaval in 2 and mesocaval in one. In 20 of the 21 peripheral shunts, the veins used for the anastomosis were less than 10 mm in diameter. There was no operative mortality. Thrombosis of the shunt occurred in 3 children (13%) and was responsible for recurrent bleeding in one who was treated later with success by a mesocaval shunt. The two other children with a thrombosed shunt are waiting, at the present time, for a mesocaval anastomosis. The volume of blood flowing through the shunt was small initially and the fall in pressure gradient was slight: therefore intraoperative angiography appeared to be a better way to assess the patency of shunts done at an early age than pressure or flow measurements. The figures recently reported by Clatworthy, with a mortality rate of 12% directly or indirectly related to repeated hemorrhage, are for us a forceful argument for early adequate management of portal hypertension in children. Until now, portal-systemic shunts have been complicated by a high frequency of thrombosis and have given discouraging results. Our results suggest that it is possible to perform portal diversion successfully on diminutive veins (down to 4 mm). From this experience early portal diversion appears to represent the treatment of choice for portal hypertension in childhood.", "contents": "Portal diversion for portal hypertension in early childhood. Twenty-three children under 6 years of age with portal hypertention were treated by portal diversion. Fourteen had cavernomatous transformation of the portal vein and 9 had an intrahepatic block due to cirrhosis (8) or congenital hepatic fibrosis (1). Portal-systemic shunts were central splenorenal in 20 patients, side-to-side portacaval in 2 and mesocaval in one. In 20 of the 21 peripheral shunts, the veins used for the anastomosis were less than 10 mm in diameter. There was no operative mortality. Thrombosis of the shunt occurred in 3 children (13%) and was responsible for recurrent bleeding in one who was treated later with success by a mesocaval shunt. The two other children with a thrombosed shunt are waiting, at the present time, for a mesocaval anastomosis. The volume of blood flowing through the shunt was small initially and the fall in pressure gradient was slight: therefore intraoperative angiography appeared to be a better way to assess the patency of shunts done at an early age than pressure or flow measurements. The figures recently reported by Clatworthy, with a mortality rate of 12% directly or indirectly related to repeated hemorrhage, are for us a forceful argument for early adequate management of portal hypertension in children. Until now, portal-systemic shunts have been complicated by a high frequency of thrombosis and have given discouraging results. Our results suggest that it is possible to perform portal diversion successfully on diminutive veins (down to 4 mm). From this experience early portal diversion appears to represent the treatment of choice for portal hypertension in childhood."} {"id": "PMID:1267503", "title": "Medical disorders in a small Caribbean island. An analysis of the disease of adults in Dominica in 1972 and 1973.", "content": "An analysis was undertaken, for the first time, of the total picture of the medical disorders of adults on a small Caribbean island. At present non-infectious diseases, especially diabetes and hypertension, are of major improtance. Parasitic infestation of the gut occurred in 50-60% of the hospital population. The pattern of diseases indicates that the island is in a transitional stage of its medical development, and that resources need not be directed to the curative as well as to public health programmes. The impact of peculiarities of local geography and customs are discussed as contributing to some of the more unusual diseases of the Caribbean.", "contents": "Medical disorders in a small Caribbean island. An analysis of the disease of adults in Dominica in 1972 and 1973. An analysis was undertaken, for the first time, of the total picture of the medical disorders of adults on a small Caribbean island. At present non-infectious diseases, especially diabetes and hypertension, are of major improtance. Parasitic infestation of the gut occurred in 50-60% of the hospital population. The pattern of diseases indicates that the island is in a transitional stage of its medical development, and that resources need not be directed to the curative as well as to public health programmes. The impact of peculiarities of local geography and customs are discussed as contributing to some of the more unusual diseases of the Caribbean."} {"id": "PMID:1267504", "title": "Culture of Schistosoma haematobium in vivo and in vitro.", "content": "The maximum rate of development of Schistosoma haematobium in the hamster was determined by examination of the most advanced worms recovered at short intervals throughout the course of development. In culture S. haematobium developed at the same rate as in the hamster up to day 31 when pairing first occurs and male worms produce some spermatozoa. In vitro males formed some spermatozoa but pairing did not take place and, probably for this reason, females did not complete sexual maturation as occurs in the host between days 57-65. Somatic growth continued in vitro and at 70 days male worms had achieved almost the same length as in the hamster at this time. The culture medium, previously used for S. mansoni, consisted of equal volumes of serum and Earle's balanced saline with a final concentration of 0.25% lactalbumin hydrolysate, 100 units/ml penicillin, 100 mug/ml streptomycin and 1% rbc. The best culture results were obtained with one particular human serum; seven other human sera gave a wide range of growth support. The samples of baboon, rhesus monkey or foetal calf sera tested provided little or no growth support but prolonged survival was possible in all the sera.", "contents": "Culture of Schistosoma haematobium in vivo and in vitro. The maximum rate of development of Schistosoma haematobium in the hamster was determined by examination of the most advanced worms recovered at short intervals throughout the course of development. In culture S. haematobium developed at the same rate as in the hamster up to day 31 when pairing first occurs and male worms produce some spermatozoa. In vitro males formed some spermatozoa but pairing did not take place and, probably for this reason, females did not complete sexual maturation as occurs in the host between days 57-65. Somatic growth continued in vitro and at 70 days male worms had achieved almost the same length as in the hamster at this time. The culture medium, previously used for S. mansoni, consisted of equal volumes of serum and Earle's balanced saline with a final concentration of 0.25% lactalbumin hydrolysate, 100 units/ml penicillin, 100 mug/ml streptomycin and 1% rbc. The best culture results were obtained with one particular human serum; seven other human sera gave a wide range of growth support. The samples of baboon, rhesus monkey or foetal calf sera tested provided little or no growth support but prolonged survival was possible in all the sera."} {"id": "PMID:1267505", "title": "Absence of liver toxicity in 2723 patients treated with hycanthone in St. Lucia.", "content": "This report is submitted not to refute the occurrence of any toxicity but to record that in St. Lucia, given reasonable care in administration and careful follow-up, we have not yet encountered jaundice, liver necrosis or other serious side effects.", "contents": "Absence of liver toxicity in 2723 patients treated with hycanthone in St. Lucia. This report is submitted not to refute the occurrence of any toxicity but to record that in St. Lucia, given reasonable care in administration and careful follow-up, we have not yet encountered jaundice, liver necrosis or other serious side effects."} {"id": "PMID:1267506", "title": "Social aspects in the changing epidemiology of malaria in the highlands of New Guinea.", "content": "The increase in movement of people both within the highlands of New Guinea and also to and fro between holo- and hyperendemic lowland areas and the highlands by policemen and semi-skilled personnel in one direction and by labourers in the other, together with a great increase in potential breeding sites, were virtually inevitable consequences of the development process as the intense communalism and geographical isolation of the highland people was broken down. Prior to the \"opening up\" of the highlands, evidence suggests that malaria had existed in an endemic and very unstable form in only a few lower altitude areas and in the populations of the perimeter villages who had contact with lowland areas. This paper traces the changes in the distribution and determinants of malaria that occurred pari passu with the development process in the highlands of Papua New Guinea between 1930 and 1970.", "contents": "Social aspects in the changing epidemiology of malaria in the highlands of New Guinea. The increase in movement of people both within the highlands of New Guinea and also to and fro between holo- and hyperendemic lowland areas and the highlands by policemen and semi-skilled personnel in one direction and by labourers in the other, together with a great increase in potential breeding sites, were virtually inevitable consequences of the development process as the intense communalism and geographical isolation of the highland people was broken down. Prior to the \"opening up\" of the highlands, evidence suggests that malaria had existed in an endemic and very unstable form in only a few lower altitude areas and in the populations of the perimeter villages who had contact with lowland areas. This paper traces the changes in the distribution and determinants of malaria that occurred pari passu with the development process in the highlands of Papua New Guinea between 1930 and 1970."} {"id": "PMID:1267507", "title": "A new design of membrane feeder incorporating an electrical blood stirring device.", "content": "A selection of the literature illustrating the origin and development of membrane feeding devices is reviewed. A new membrane feeding device-incorporating an electrical stirrer is described and its mode of operation explained. The sedimentation of red blood cells within a membrane feeding device, and the consequent hazard to arthropod feeding, is prevented by the use of the redesigned feeding unit and electrical blood stirrer. The mosquito feeding rate and mean blood meal size (mg) were unaffected by the action of the stirrer when compared to those in an unstirred control. Mosquitoes, bugs, ticks and tsetse flies have been fed sucessfully using the apparatus.", "contents": "A new design of membrane feeder incorporating an electrical blood stirring device. A selection of the literature illustrating the origin and development of membrane feeding devices is reviewed. A new membrane feeding device-incorporating an electrical stirrer is described and its mode of operation explained. The sedimentation of red blood cells within a membrane feeding device, and the consequent hazard to arthropod feeding, is prevented by the use of the redesigned feeding unit and electrical blood stirrer. The mosquito feeding rate and mean blood meal size (mg) were unaffected by the action of the stirrer when compared to those in an unstirred control. Mosquitoes, bugs, ticks and tsetse flies have been fed sucessfully using the apparatus."} {"id": "PMID:1267510", "title": "Epidemiological patterns of cutaneous leishmaniasis in Panama. I. Epidemics among small groups of settlers.", "content": "Epidemic of cutaneous leishmanniasis among a small group of people established in a Panamanian forested area was studied. The first settlers arrived in June 1971, and by June 1973 there were 37 persons, 33 of whom had no previous history of the disease. Epidemiological surveys were made in June 1973 and March 1974. The disease developed in 14 (42.4%) of the 33 susceptible persons by June 1973, with an exposure time ranging from one to 14 months. The last case occurred in April 1973, and no new cases were observed during the ensuing 11 months. Two (15.4%) of 13 dogs examined were found with cutaneous leishmaniasis, but none of 41 feral mammals studied, mainly terrestrial rodents, was infected. Four leishmanial strains characterized, three from patients and one from a dog, were identified as Leishmania braziliensis. Phlebotomine sandfly population composition was studied and the probable vectors involved in the transmission to man were determined.", "contents": "Epidemiological patterns of cutaneous leishmaniasis in Panama. I. Epidemics among small groups of settlers. Epidemic of cutaneous leishmanniasis among a small group of people established in a Panamanian forested area was studied. The first settlers arrived in June 1971, and by June 1973 there were 37 persons, 33 of whom had no previous history of the disease. Epidemiological surveys were made in June 1973 and March 1974. The disease developed in 14 (42.4%) of the 33 susceptible persons by June 1973, with an exposure time ranging from one to 14 months. The last case occurred in April 1973, and no new cases were observed during the ensuing 11 months. Two (15.4%) of 13 dogs examined were found with cutaneous leishmaniasis, but none of 41 feral mammals studied, mainly terrestrial rodents, was infected. Four leishmanial strains characterized, three from patients and one from a dog, were identified as Leishmania braziliensis. Phlebotomine sandfly population composition was studied and the probable vectors involved in the transmission to man were determined."} {"id": "PMID:1267511", "title": "Epidemiological patterns of cutaneous leishmaniasis in Panama. II. Incidental occurrence of cases in non-endemic settlements.", "content": "Epidemiological studies on cutaneous leishmaniasis were carried out in a settlement in the Bayano region, Republic of Panama, during 1971-72. This settlement was established about 12 years earlier for the purpose of cattle raising by small groups of settlers. The primary forest was cut and cleared and the area planted with grass. The presence of active cases of cutaneous leishmaniasis among humans and animals, both domestic and ferals, was investigated. In addition, phlebotomine sandflies were collected to determine their species composition. In 1971, nine of the 161 persons interviewed had active lesions; all but one of the patients were males and of these seven were adults. Five (9%) of 55 dogs and one (3%) of 33 feral mammals examined also were found infected. Strains of the parasite infecting both humans and animals were characterized as Leishmania braziliensis. About 60% of the sandflies collected belong to four man-biting species previously incriminated as vectors of human cutaneous leishmaniasis in Panama. The extensive pasture, together with periodic applications of insecticides in the houses by the antimalarial agency in this country, provided an effective barrier against transmission within the settlement itself. However, both humans and dogs acquired the disease during excursions into the surrounding forest. No new cases were found in 1972.", "contents": "Epidemiological patterns of cutaneous leishmaniasis in Panama. II. Incidental occurrence of cases in non-endemic settlements. Epidemiological studies on cutaneous leishmaniasis were carried out in a settlement in the Bayano region, Republic of Panama, during 1971-72. This settlement was established about 12 years earlier for the purpose of cattle raising by small groups of settlers. The primary forest was cut and cleared and the area planted with grass. The presence of active cases of cutaneous leishmaniasis among humans and animals, both domestic and ferals, was investigated. In addition, phlebotomine sandflies were collected to determine their species composition. In 1971, nine of the 161 persons interviewed had active lesions; all but one of the patients were males and of these seven were adults. Five (9%) of 55 dogs and one (3%) of 33 feral mammals examined also were found infected. Strains of the parasite infecting both humans and animals were characterized as Leishmania braziliensis. About 60% of the sandflies collected belong to four man-biting species previously incriminated as vectors of human cutaneous leishmaniasis in Panama. The extensive pasture, together with periodic applications of insecticides in the houses by the antimalarial agency in this country, provided an effective barrier against transmission within the settlement itself. However, both humans and dogs acquired the disease during excursions into the surrounding forest. No new cases were found in 1972."} {"id": "PMID:1267512", "title": "A new method of external cardiac massage to improve diastolic augmentation and prolong survival time.", "content": "Experiments were performed on 50 dogs to determine the reason for unsatisfactory survival rates following closed-chest cardiac massage and to help develop new means for increasing survival following acute myocardial infarction and other causes of cardiac arrest. A new technique, named the countermassage method, was subsequently developed. Coronary and carotid flows after use of countermassage following cardiac arrest were increased 1.4 and 2 times, respectively, in contrast to flows obtained during manual closed-chest cardiac massage. These increases brought flows up to normal levels. We also tried to determine whether survival could be extended by this method to facilitate clinical treatment such as defibrillation or placing a temporary pacemaker catheter under fluoroscopic control, which are hard to accomplish during the brief time permitted by conventional closed-chest cardiac massage.", "contents": "A new method of external cardiac massage to improve diastolic augmentation and prolong survival time. Experiments were performed on 50 dogs to determine the reason for unsatisfactory survival rates following closed-chest cardiac massage and to help develop new means for increasing survival following acute myocardial infarction and other causes of cardiac arrest. A new technique, named the countermassage method, was subsequently developed. Coronary and carotid flows after use of countermassage following cardiac arrest were increased 1.4 and 2 times, respectively, in contrast to flows obtained during manual closed-chest cardiac massage. These increases brought flows up to normal levels. We also tried to determine whether survival could be extended by this method to facilitate clinical treatment such as defibrillation or placing a temporary pacemaker catheter under fluoroscopic control, which are hard to accomplish during the brief time permitted by conventional closed-chest cardiac massage."} {"id": "PMID:1267513", "title": "Surgical treatment of congenital heart disease with special reference to the application of hypothermia.", "content": "This report presents the results of operation for congenital heart disease using two different methods of hypothermia: (1) Immersion hypothermia alone. Of the 782 patients who underwent open-heart operations using this method the results were good in patients whose intracardiac surgical repair took less than one hour (average mortality rate, 5.6%). (2) Rapid extracorporeal cooling. Of the 269 patients with congenital heart diseases such as ventricular septal defect, tetralogy of Fallot, or atrioventricular canal with low cardiac reserve who underwent operation with mild to moderate hypothermia utilizing rapid extracorporeal cooling, the mortality was 11.2%. In the 151 patients with more serious defects, including the extreme form of tetralogy of Fallot, single ventricle, and truncus arteriosus, who underwent open-heart operations with deep hypothermia utilizing extracorporeal cooling, the mortality rate was 15.2%.", "contents": "Surgical treatment of congenital heart disease with special reference to the application of hypothermia. This report presents the results of operation for congenital heart disease using two different methods of hypothermia: (1) Immersion hypothermia alone. Of the 782 patients who underwent open-heart operations using this method the results were good in patients whose intracardiac surgical repair took less than one hour (average mortality rate, 5.6%). (2) Rapid extracorporeal cooling. Of the 269 patients with congenital heart diseases such as ventricular septal defect, tetralogy of Fallot, or atrioventricular canal with low cardiac reserve who underwent operation with mild to moderate hypothermia utilizing rapid extracorporeal cooling, the mortality was 11.2%. In the 151 patients with more serious defects, including the extreme form of tetralogy of Fallot, single ventricle, and truncus arteriosus, who underwent open-heart operations with deep hypothermia utilizing extracorporeal cooling, the mortality rate was 15.2%."} {"id": "PMID:1267514", "title": "Mustard's operation for transposition of the great arteries complicated by juxtaposition of the atrial appendages.", "content": "Six patients were seen with complete left-sided juxtaposition of the atrial appendages (LJAA) in a series of 366 consecutive Mustard operations for transposition of the great arteries. All 6 patients had situs solitus of the viscera and atria with concordant atrioventricular relationship. D-transposition was present in 3 patients and L-transposition in the other 3; all 6 had associated cardiac anomalies. The diagnosis of LJAA was first made at operation, although angiocardiographic recognition is possible. The size of the right atrium is small in the presence of this anomaly, and direct cannulation of the venae cavae and enlargement of the pulmonary venous atrium are therefore recommended.", "contents": "Mustard's operation for transposition of the great arteries complicated by juxtaposition of the atrial appendages. Six patients were seen with complete left-sided juxtaposition of the atrial appendages (LJAA) in a series of 366 consecutive Mustard operations for transposition of the great arteries. All 6 patients had situs solitus of the viscera and atria with concordant atrioventricular relationship. D-transposition was present in 3 patients and L-transposition in the other 3; all 6 had associated cardiac anomalies. The diagnosis of LJAA was first made at operation, although angiocardiographic recognition is possible. The size of the right atrium is small in the presence of this anomaly, and direct cannulation of the venae cavae and enlargement of the pulmonary venous atrium are therefore recommended."} {"id": "PMID:1267515", "title": "Microporous expanded polytetrafluoroethylene arterial prosthesis for construction of aortopulmonary shunts: experimental and clinical results.", "content": "A new microporous, expanded polytetrafluoroethylene arterial prosthesis was evaluated in dogs. The material appears to produce an adequate prosthesis for aortopulmonary anastomosis in animals and can conduct a high rate of blood flow. The graft has been used in 3 patients with pulmonary atresia aged 2 days, 2 months, and 6 months. Thus far all patients are well, growing, and have a loud shunt murmur. The desirable features of this type of anastomosis are presented.", "contents": "Microporous expanded polytetrafluoroethylene arterial prosthesis for construction of aortopulmonary shunts: experimental and clinical results. A new microporous, expanded polytetrafluoroethylene arterial prosthesis was evaluated in dogs. The material appears to produce an adequate prosthesis for aortopulmonary anastomosis in animals and can conduct a high rate of blood flow. The graft has been used in 3 patients with pulmonary atresia aged 2 days, 2 months, and 6 months. Thus far all patients are well, growing, and have a loud shunt murmur. The desirable features of this type of anastomosis are presented."} {"id": "PMID:1267516", "title": "Traumatic aortic rupture: roentgenographic indications for angiography.", "content": "The principal radiological indication for thoracic aortography following blunt chest trauma has been a widened mediastinum on chest roentgenogram. The presence or absence of sixteen findings on 100 cm anteroposterior supine chest roentgenograms were noted and compared in 47 consecutive patients who underwent aortography following blunt thoracic trauma and 100 patients without trauma. On the basis of our data, we propose six radiological indications for thoracic aortography following chest trauma: mediastinum greater than 8 cm on 100 cm AP supine chest film; tracheal shift to the right; blurring of the normally sharp outline of the aorta; obliteration of the medial aspect of the apex of the left upper lobe; opacification of the clear space between the aorta and pulmonary artery; and depression of the left main bronchus below 40 degrees.", "contents": "Traumatic aortic rupture: roentgenographic indications for angiography. The principal radiological indication for thoracic aortography following blunt chest trauma has been a widened mediastinum on chest roentgenogram. The presence or absence of sixteen findings on 100 cm anteroposterior supine chest roentgenograms were noted and compared in 47 consecutive patients who underwent aortography following blunt thoracic trauma and 100 patients without trauma. On the basis of our data, we propose six radiological indications for thoracic aortography following chest trauma: mediastinum greater than 8 cm on 100 cm AP supine chest film; tracheal shift to the right; blurring of the normally sharp outline of the aorta; obliteration of the medial aspect of the apex of the left upper lobe; opacification of the clear space between the aorta and pulmonary artery; and depression of the left main bronchus below 40 degrees."} {"id": "PMID:1267517", "title": "Left subcostal insertion of the sutureless myocardial electrode.", "content": "This report describes the use of a left subcostal extrapleural supradiaphragmatic approach to the heart for myocardial sutureless electrode insertion. Electrode insertion by this approach has consistently produced low electrode thresholds, and the ability to insert electrodes into the left ventricle or septal area of the right ventricle is considered an advantage. This technique has now been used in 52 patients. Postoperative morbidity and complications have been minimal. The procedure appears to be well tolerated in the elderly, poor-risk patient and has been a useful technique for revision of failed pacemaker systems. We believe this procedure reduces the indications for permanent transvenous pacing.", "contents": "Left subcostal insertion of the sutureless myocardial electrode. This report describes the use of a left subcostal extrapleural supradiaphragmatic approach to the heart for myocardial sutureless electrode insertion. Electrode insertion by this approach has consistently produced low electrode thresholds, and the ability to insert electrodes into the left ventricle or septal area of the right ventricle is considered an advantage. This technique has now been used in 52 patients. Postoperative morbidity and complications have been minimal. The procedure appears to be well tolerated in the elderly, poor-risk patient and has been a useful technique for revision of failed pacemaker systems. We believe this procedure reduces the indications for permanent transvenous pacing."} {"id": "PMID:1267518", "title": "Plasmacytoma arising in a pacemaker pocket.", "content": "A 48-year-old man developed a plasmacytoma in the subcutaneous pocket of a titanium covered pulse generator that had been inserted sixteen months previously. The tumor represented a cutaneous manifestation of myelomatosis. The presence of a pacemaker may affect the detection and treatment of tumors arising in the region of pulse generator pockets. Possible cause-and-effect relationships are explored.", "contents": "Plasmacytoma arising in a pacemaker pocket. A 48-year-old man developed a plasmacytoma in the subcutaneous pocket of a titanium covered pulse generator that had been inserted sixteen months previously. The tumor represented a cutaneous manifestation of myelomatosis. The presence of a pacemaker may affect the detection and treatment of tumors arising in the region of pulse generator pockets. Possible cause-and-effect relationships are explored."} {"id": "PMID:1267519", "title": "Embolization of disc occluder of a Wada-Cutter mitral prosthesis with survival.", "content": "The second recorded survivor following emergency prosthesis replacement after embolization of the Teflon disc occluder of a Wada-Cutter mitral valve is reported. Difficulties encountered while attempting to locate the missing occluder are presented and a useful operative technique for aortic control is described. A plea is made for incorporation of a radiopaque material during manufacture of all future valve poppets.", "contents": "Embolization of disc occluder of a Wada-Cutter mitral prosthesis with survival. The second recorded survivor following emergency prosthesis replacement after embolization of the Teflon disc occluder of a Wada-Cutter mitral valve is reported. Difficulties encountered while attempting to locate the missing occluder are presented and a useful operative technique for aortic control is described. A plea is made for incorporation of a radiopaque material during manufacture of all future valve poppets."} {"id": "PMID:1267521", "title": "Primary repair of esophageal atresia without staging or preliminary gastrostomy.", "content": "Twenty-two neonates with esophageal atresia and a distal tracheoesophageal fistula were treated by primary repair. Only if an anastomotic leak was demonstrated was a tube gastrostomy for decompression with trangastric placement of a duodenal tube for feeding performed. Twelve newborns were classified as high-risk by the presence of prematurity with low birth weight (less than 2,250 gm), significant pneumonia, or obvious significant associated anomalies. There was one operative death and 1 late death. Three babies required a tube gastrotomy and duodenal tube for anastomotic leaks. All 20 survivors are symptom free and thriving. Progress in perioperative management of neonates with esophageal atresia may obviate the need for routine gastrostomy and for staging of high-risk newborns.", "contents": "Primary repair of esophageal atresia without staging or preliminary gastrostomy. Twenty-two neonates with esophageal atresia and a distal tracheoesophageal fistula were treated by primary repair. Only if an anastomotic leak was demonstrated was a tube gastrostomy for decompression with trangastric placement of a duodenal tube for feeding performed. Twelve newborns were classified as high-risk by the presence of prematurity with low birth weight (less than 2,250 gm), significant pneumonia, or obvious significant associated anomalies. There was one operative death and 1 late death. Three babies required a tube gastrotomy and duodenal tube for anastomotic leaks. All 20 survivors are symptom free and thriving. Progress in perioperative management of neonates with esophageal atresia may obviate the need for routine gastrostomy and for staging of high-risk newborns."} {"id": "PMID:1267522", "title": "Prevention of increased hemoglobin-oxygen affinity in open-heart operations with inosine-phosphate-pyruvate solution.", "content": "In a control group of 32 patients undergoing open-heart operation, erythrocyte 2,3-diphosphoglycerate (2,3-DPG) declined progressively during the course of perfusion from a prebypass mean of 17.00 to 11.29 mu M per gram of hemoglobin at the end of bypass. The decrease was greater than that attributable merely to dilution of the patients' cells with the 2,3-DPG-deficient donor cells used to prime the pump oxygenator circuit. Administration of 300 mg of allopurinol, to prevent the conversion of inosine to uric acid, every 8 hours during the 24 hours prior to operation in 11 patients did not prevent the 2,3-DPG decrease during heart-lung bypass: prebypass, 18.31; postbypass, 13.56 mu M/gm Hgb. The mean P50 for both these groups combined decreased from a prebypass mean of 25.7 to a postbypass level of 21.9 torr. A solution of 0.1 M inosine, 0.1 M pyruvate, and 0.066 M phosphate (IPP) in a dosage of 7.5 ml per kologram of body weight prevented the 2,3-DPG decrease: prebypass, 15.74; postbypass, 14.85. Administration of 15 ml per kilogram of IPP in 15 patients preserved 2,3-DPG: prebypass, 18.09; postbypass, 18.52. The P50 remained unchanged in this last group. The method of providing for myocardial oxygen requirements during bypass was not standardized, and therefore the protective effect of IPP against ischemic damage in patients undergoing aortic valve replacement or myocardial revascularization could not be evaluated. No deleterious effects of IPP were noted.", "contents": "Prevention of increased hemoglobin-oxygen affinity in open-heart operations with inosine-phosphate-pyruvate solution. In a control group of 32 patients undergoing open-heart operation, erythrocyte 2,3-diphosphoglycerate (2,3-DPG) declined progressively during the course of perfusion from a prebypass mean of 17.00 to 11.29 mu M per gram of hemoglobin at the end of bypass. The decrease was greater than that attributable merely to dilution of the patients' cells with the 2,3-DPG-deficient donor cells used to prime the pump oxygenator circuit. Administration of 300 mg of allopurinol, to prevent the conversion of inosine to uric acid, every 8 hours during the 24 hours prior to operation in 11 patients did not prevent the 2,3-DPG decrease during heart-lung bypass: prebypass, 18.31; postbypass, 13.56 mu M/gm Hgb. The mean P50 for both these groups combined decreased from a prebypass mean of 25.7 to a postbypass level of 21.9 torr. A solution of 0.1 M inosine, 0.1 M pyruvate, and 0.066 M phosphate (IPP) in a dosage of 7.5 ml per kologram of body weight prevented the 2,3-DPG decrease: prebypass, 15.74; postbypass, 14.85. Administration of 15 ml per kilogram of IPP in 15 patients preserved 2,3-DPG: prebypass, 18.09; postbypass, 18.52. The P50 remained unchanged in this last group. The method of providing for myocardial oxygen requirements during bypass was not standardized, and therefore the protective effect of IPP against ischemic damage in patients undergoing aortic valve replacement or myocardial revascularization could not be evaluated. No deleterious effects of IPP were noted."} {"id": "PMID:1267523", "title": "Phasic coronary flow: intraoperative evaluation of flow distribution, myocardial function, and reactive hyperemic response.", "content": "Using visual inspection of phasic flow patterns and understanding their physical determinants, intraoperative decisions regarding flow distribution, function of revascularized myocardium, and collateral communications can be made. Mean flow measurements cannot provide this information. Systolic compressive forces across most of the normally contracting left ventricle limit systolic myocardial perfusion. Consequently, normal flow through the left anterior descending, left circumflex, and dominant right coronary artery (supplying the inferior left ventricle) is predominantly diastolic (greater than 60%) and remains so during reactive hyperemia. Representative examples from 100 consecutive revascularizations are presented showing that when more than 40% of flow is systolic in the right coronary artery, high mean flows (greater than 100 ml/min) may go predominantly to the right rather than the left ventricle; in the case of the left coronary artery, high mean flow may supply myocardium undergoing infarction or replaced by scar rather than normally contracting muscle. When more than 60% of flow is diastolic without reactive hyperemia, borderline mean flow (40 to 60 ml/min) may indicate lack of distal ischemia rather than fixed distal resistance.", "contents": "Phasic coronary flow: intraoperative evaluation of flow distribution, myocardial function, and reactive hyperemic response. Using visual inspection of phasic flow patterns and understanding their physical determinants, intraoperative decisions regarding flow distribution, function of revascularized myocardium, and collateral communications can be made. Mean flow measurements cannot provide this information. Systolic compressive forces across most of the normally contracting left ventricle limit systolic myocardial perfusion. Consequently, normal flow through the left anterior descending, left circumflex, and dominant right coronary artery (supplying the inferior left ventricle) is predominantly diastolic (greater than 60%) and remains so during reactive hyperemia. Representative examples from 100 consecutive revascularizations are presented showing that when more than 40% of flow is systolic in the right coronary artery, high mean flows (greater than 100 ml/min) may go predominantly to the right rather than the left ventricle; in the case of the left coronary artery, high mean flow may supply myocardium undergoing infarction or replaced by scar rather than normally contracting muscle. When more than 60% of flow is diastolic without reactive hyperemia, borderline mean flow (40 to 60 ml/min) may indicate lack of distal ischemia rather than fixed distal resistance."} {"id": "PMID:1267524", "title": "Retrograde coronary capillary perfusion for prevention and reversal of cardiogenic shock in experimental myocardial infarction.", "content": "The coronary sinus and coronary veins offer an access route for delivery of increased oxygen to ischemic myocardium surrounding the central dead zone of heart muscle in cardiogenic shock due to myocardial infarction. This investigation was conducted to determine if transvenous retrograde coronary capillary perfusion with oxygenated blood would prevent and reverse cardiogenic shock in experimental myocardial infarction produced by acute ligation of the circumflex and anterior descending left coronary artery in dogs. Cardiac output and systemic blood pressure were maintained near control values for up to 30 minutes when total left coronary ligation was accompanied by coronary retroperfusion. Conversely, both cariac output and systemic blood pressure fell to severe cardiogenic shocks levels within 2 minutes of total left cardiogenic shock levels within 2 minutes of total left coronary artery occlusion without retrograde flow or when retrograde flow was terminated 5 to 30 minutes following simultaneous coronary ligation and institution of retrograde flow.", "contents": "Retrograde coronary capillary perfusion for prevention and reversal of cardiogenic shock in experimental myocardial infarction. The coronary sinus and coronary veins offer an access route for delivery of increased oxygen to ischemic myocardium surrounding the central dead zone of heart muscle in cardiogenic shock due to myocardial infarction. This investigation was conducted to determine if transvenous retrograde coronary capillary perfusion with oxygenated blood would prevent and reverse cardiogenic shock in experimental myocardial infarction produced by acute ligation of the circumflex and anterior descending left coronary artery in dogs. Cardiac output and systemic blood pressure were maintained near control values for up to 30 minutes when total left coronary ligation was accompanied by coronary retroperfusion. Conversely, both cariac output and systemic blood pressure fell to severe cardiogenic shocks levels within 2 minutes of total left cardiogenic shock levels within 2 minutes of total left coronary artery occlusion without retrograde flow or when retrograde flow was terminated 5 to 30 minutes following simultaneous coronary ligation and institution of retrograde flow."} {"id": "PMID:1267525", "title": "Events related to microembolism during extracorporeal perfusion in man: effectiveness of in-line filtration recorded by ultrasound.", "content": "Microparticle generation during cardiopulmonary bypass was monitored continuously in 60 adult patients who underwent open-heart operations. Echo-ultrasound transducers of 5 mHz frequency were interposed in a bubble oxygenator arterial line proximal and distal to a commercially available micropore filter. Ordinary perfusion events correlated with an increase in embolic counts and were recorded graphically. Calculation of filter efficiency revealed that all filters decreased measurable embolic counts. Platelet and leukocyte determinations and plasma hemoglobin values were not altered beyond limits ordinarily encountered during perfusion without filters. No patient in any filter group experienced postoperative respiratory distress, diffuse pulmonary infiltrate, or low PaO2. The 20 mu woven nylon mesh filter and the Dacron-wool filter showed greater than 90% effectiveness in removing recorded particles. Insertion of a cardiotomy filter did not appreciably alter recorded embolic counts distal to the arterial line filter.", "contents": "Events related to microembolism during extracorporeal perfusion in man: effectiveness of in-line filtration recorded by ultrasound. Microparticle generation during cardiopulmonary bypass was monitored continuously in 60 adult patients who underwent open-heart operations. Echo-ultrasound transducers of 5 mHz frequency were interposed in a bubble oxygenator arterial line proximal and distal to a commercially available micropore filter. Ordinary perfusion events correlated with an increase in embolic counts and were recorded graphically. Calculation of filter efficiency revealed that all filters decreased measurable embolic counts. Platelet and leukocyte determinations and plasma hemoglobin values were not altered beyond limits ordinarily encountered during perfusion without filters. No patient in any filter group experienced postoperative respiratory distress, diffuse pulmonary infiltrate, or low PaO2. The 20 mu woven nylon mesh filter and the Dacron-wool filter showed greater than 90% effectiveness in removing recorded particles. Insertion of a cardiotomy filter did not appreciably alter recorded embolic counts distal to the arterial line filter."} {"id": "PMID:1267526", "title": "Supravalvular stenosing ring of the left atrium.", "content": "Two patients with supravalvular stenosing ring of the left atrium are described. In 1 patient with an associated ventricular septal defect and Wolff-Parkinson-White syndrome, the diagnosis of supravalvular stenosing ring was only suspected. This patient underwent correction but died 34 days after the operation because of pulmonary embolism. In the second patient a preoperative diagnosis was not made, and this contributed to his death following correction of tetralogy of Fallot. The association of these two anomalies is very rare. Differential diagnosis from other congenital anomalies producing obstruction of left atrial flow is discussed. The divergent microscopical features of the membrane in supravalvular stenosing ring of the left atrium and in cor triatriatum are described. The value of cardiac catheterization, angiography, and echocardiography as diagnostic aids is emphasized. The hazards of not recognizing and diagnosing this anomaly when associated with other cardiac malformations are pointed out.", "contents": "Supravalvular stenosing ring of the left atrium. Two patients with supravalvular stenosing ring of the left atrium are described. In 1 patient with an associated ventricular septal defect and Wolff-Parkinson-White syndrome, the diagnosis of supravalvular stenosing ring was only suspected. This patient underwent correction but died 34 days after the operation because of pulmonary embolism. In the second patient a preoperative diagnosis was not made, and this contributed to his death following correction of tetralogy of Fallot. The association of these two anomalies is very rare. Differential diagnosis from other congenital anomalies producing obstruction of left atrial flow is discussed. The divergent microscopical features of the membrane in supravalvular stenosing ring of the left atrium and in cor triatriatum are described. The value of cardiac catheterization, angiography, and echocardiography as diagnostic aids is emphasized. The hazards of not recognizing and diagnosing this anomaly when associated with other cardiac malformations are pointed out."} {"id": "PMID:1267527", "title": "Constrictive pericarditis.", "content": "A patient with constrictive pericarditis following an open-heart operation without sepsis is discussed. In the absence of sepsis, it has been widely held that this complication does not develop following an open-heart procedure. The fatal outcome in this patient could have been avoided had such an association been known.", "contents": "Constrictive pericarditis. A patient with constrictive pericarditis following an open-heart operation without sepsis is discussed. In the absence of sepsis, it has been widely held that this complication does not develop following an open-heart procedure. The fatal outcome in this patient could have been avoided had such an association been known."} {"id": "PMID:1267528", "title": "A simple technique for obtaining Pap smears of the esophagus.", "content": "A simple method for obtaining Papanicolaou smears of the esophagus is described. The procedure is easy to perform, does not require specialized equipment, and is a useful adjuvant to direct esophageal biospy.", "contents": "A simple technique for obtaining Pap smears of the esophagus. A simple method for obtaining Papanicolaou smears of the esophagus is described. The procedure is easy to perform, does not require specialized equipment, and is a useful adjuvant to direct esophageal biospy."} {"id": "PMID:1267529", "title": "A method of outflow tract reconstruction in tetralogy of Fallot with anomalous anterior descending coronary artery.", "content": "An anomalous anterior descending coronary artery that arises from the right coronary and crosses the right ventricle outflow tract can compromise corrective operations for tetralogy of Fallot. The only safe method of outflow tract reconstruction reported until now is the use of a tubular graft from the right ventricle to the pulmonary artery. We report successful reconstruction of the outflow tract by placing a standard fabric path under the mobilized anomalous coronary artery. This technique should avoid the late complications of tubular conduits by preserving the natural posterior wall of the outflow tract for growth.", "contents": "A method of outflow tract reconstruction in tetralogy of Fallot with anomalous anterior descending coronary artery. An anomalous anterior descending coronary artery that arises from the right coronary and crosses the right ventricle outflow tract can compromise corrective operations for tetralogy of Fallot. The only safe method of outflow tract reconstruction reported until now is the use of a tubular graft from the right ventricle to the pulmonary artery. We report successful reconstruction of the outflow tract by placing a standard fabric path under the mobilized anomalous coronary artery. This technique should avoid the late complications of tubular conduits by preserving the natural posterior wall of the outflow tract for growth."} {"id": "PMID:1267530", "title": "Patch closure of the ductus arteriosus: an improved method.", "content": "An improved surgical procedure for patch closure of the ductus arteriosus under cardiopulmonary bypass is presented. A patch with a Fogarty catheter inserted through its center is used. The catheter is insinuated into the aorta through a pulmonary arteriotomy under normothermic cardiopulmonary bypass. An inflated intraaortic balloon is made to plug the orifice of the ductus using gentle traction on the catheter. The catheter may be slanted in any direction that is convenient to provide satisfactory visualization of the operative field.", "contents": "Patch closure of the ductus arteriosus: an improved method. An improved surgical procedure for patch closure of the ductus arteriosus under cardiopulmonary bypass is presented. A patch with a Fogarty catheter inserted through its center is used. The catheter is insinuated into the aorta through a pulmonary arteriotomy under normothermic cardiopulmonary bypass. An inflated intraaortic balloon is made to plug the orifice of the ductus using gentle traction on the catheter. The catheter may be slanted in any direction that is convenient to provide satisfactory visualization of the operative field."} {"id": "PMID:1267531", "title": "Improved technique for bedside insertion of the Swan-Ganz pulmonary artery catheter.", "content": "A method for inserting the Swan-Ganz pulmonary artery ballon has proved this to be a safe and efficient approach to hemodynamic monitoring of critically ill patients, frequently catheter utilizing direct subclavian venipuncture is presented. Our experience eliminating the need for bedside surgical procedures.", "contents": "Improved technique for bedside insertion of the Swan-Ganz pulmonary artery catheter. A method for inserting the Swan-Ganz pulmonary artery ballon has proved this to be a safe and efficient approach to hemodynamic monitoring of critically ill patients, frequently catheter utilizing direct subclavian venipuncture is presented. Our experience eliminating the need for bedside surgical procedures."} {"id": "PMID:1267533", "title": "Possible role of histamine receptors in cardiovascular responses to 5-hydroxytryptamine in the chicken.", "content": "Mepyramine (a selective H1-histamine receptor antagonist) and burimamide (a selective H2-receptor antagonist) specifically and equally modify the systemic hypotensive responses to both serotonin and histamine. Results suggest that both H1- and H2-histamine receptors in part mediate systemic arterial depressor and venous pressor responses to 5-HT in the domestic chicken.", "contents": "Possible role of histamine receptors in cardiovascular responses to 5-hydroxytryptamine in the chicken. Mepyramine (a selective H1-histamine receptor antagonist) and burimamide (a selective H2-receptor antagonist) specifically and equally modify the systemic hypotensive responses to both serotonin and histamine. Results suggest that both H1- and H2-histamine receptors in part mediate systemic arterial depressor and venous pressor responses to 5-HT in the domestic chicken."} {"id": "PMID:1267534", "title": "Studies on the neuropharmacology of tert-butylurea in mice.", "content": "Tertiary butylurea has been investigated neuropharmacologically in mice and rats, and the results indicate that the compound possesses a marked CNS activity. It exhibited a pronounced activity against pentetrazole-induced convulsions and lethality, but the protection against strychnine-induced convulsions and lethality, was only partial. A significant prolongation of pentobarbital sleeping time by a subsedative dose of tert-butylurea was also observed. Protection afforded by tert-butylurea against tremorine-induced tremors and the intensity of its analgesic activity were both of moderate degree. In a subsedative dose range, tert-butylurea exhibited motor incoordination and behavioral effects with a decrease in the minor and the major movements of animals, as apparent from the treadmill and activity meter experiments respectively. The compound, however, does not seem to be a potent sedative-hypnotic agent, although there is a fairly good margin of safety between the hypnotic and the lethal dose orally. The anti-pentetrazole activity of tert-butylurea suggests its possible effectiveness against 'petit mal' seizures and, therefore, calls for additional studies to evaluate the anticonvulsant activity of tert-butylurea.", "contents": "Studies on the neuropharmacology of tert-butylurea in mice. Tertiary butylurea has been investigated neuropharmacologically in mice and rats, and the results indicate that the compound possesses a marked CNS activity. It exhibited a pronounced activity against pentetrazole-induced convulsions and lethality, but the protection against strychnine-induced convulsions and lethality, was only partial. A significant prolongation of pentobarbital sleeping time by a subsedative dose of tert-butylurea was also observed. Protection afforded by tert-butylurea against tremorine-induced tremors and the intensity of its analgesic activity were both of moderate degree. In a subsedative dose range, tert-butylurea exhibited motor incoordination and behavioral effects with a decrease in the minor and the major movements of animals, as apparent from the treadmill and activity meter experiments respectively. The compound, however, does not seem to be a potent sedative-hypnotic agent, although there is a fairly good margin of safety between the hypnotic and the lethal dose orally. The anti-pentetrazole activity of tert-butylurea suggests its possible effectiveness against 'petit mal' seizures and, therefore, calls for additional studies to evaluate the anticonvulsant activity of tert-butylurea."} {"id": "PMID:1267535", "title": "Acute changes in ventilation and blood pressure induced by inhalation of tobacco smoke.", "content": "Inhalation of cigarette smoke through a tracheal cannula was induced in cats anesthetized with pentobarbital. Smoking of tobacco cigarettes produced increased ventilation and systemic hypertension, which were found to be due to their nicotine content. Respiratory stimulation and the increase in diastolic pressure were abolished by acute section of 'buffer nerves', but the mediation of carotid nerves was more important than that of the vagi for evoking reflex hyperventilation. Tobacco smoking induced a marked increase in the frequency of chemosensory impulses recorded from the carotid nerves, an effect due to its nicotine content.", "contents": "Acute changes in ventilation and blood pressure induced by inhalation of tobacco smoke. Inhalation of cigarette smoke through a tracheal cannula was induced in cats anesthetized with pentobarbital. Smoking of tobacco cigarettes produced increased ventilation and systemic hypertension, which were found to be due to their nicotine content. Respiratory stimulation and the increase in diastolic pressure were abolished by acute section of 'buffer nerves', but the mediation of carotid nerves was more important than that of the vagi for evoking reflex hyperventilation. Tobacco smoking induced a marked increase in the frequency of chemosensory impulses recorded from the carotid nerves, an effect due to its nicotine content."} {"id": "PMID:1267536", "title": "Respiratory and circulatory reflexes induced by nicotine injections: role of carotid body chemoreceptors.", "content": "Intravenous and intracarotid injections of nicotine were delivered to cats anesthetized with pentobarbital. Low doses of nicotine were found to induce reflex hyperventilation and hypertension, mainly due to excitation of carotid body chemoreceptors. The frequency of discharge of carotid nerve chemosensory fibres was increased by nicotine in doses as low as 1 mug/kg when injected intravenously and 50 ng when injected into the carotid artery. Nicotine also activates vagal afferent fibres; some of them produce reflex excitation of the respiratory and vasomotor centres, but others provoke reflex inhibition. High doses of nicotine can act directly upon the medulla provoking acceleration or arrest of ventilation. Nicotine can also induce 'late' changes of b.p. (delay 5 sec or more) which are not mediated by the carotid or vagus nerves.", "contents": "Respiratory and circulatory reflexes induced by nicotine injections: role of carotid body chemoreceptors. Intravenous and intracarotid injections of nicotine were delivered to cats anesthetized with pentobarbital. Low doses of nicotine were found to induce reflex hyperventilation and hypertension, mainly due to excitation of carotid body chemoreceptors. The frequency of discharge of carotid nerve chemosensory fibres was increased by nicotine in doses as low as 1 mug/kg when injected intravenously and 50 ng when injected into the carotid artery. Nicotine also activates vagal afferent fibres; some of them produce reflex excitation of the respiratory and vasomotor centres, but others provoke reflex inhibition. High doses of nicotine can act directly upon the medulla provoking acceleration or arrest of ventilation. Nicotine can also induce 'late' changes of b.p. (delay 5 sec or more) which are not mediated by the carotid or vagus nerves."} {"id": "PMID:1267537", "title": "Cardiovascular tryptamine receptors in the chicken.", "content": "The effects of \"M\"-receptor blockers (atropine and morphine), \"D\"-receptor blockers (dibenamine, dibenzyline, methysergide) and a ganglion blocking agent (mecamylamine) were studied to characterize cardiovascular tryptaminergic receptors in domestic fowl. This study showed the presence of both \"M\" and \"D\" tryptaminergic receptors (both mediating systemic hypotension) and also other \"D\"-receptors, which mediate arterial and venous hypertensive responses to 5-HT. There appear to be interactions of tryptaminergic, cholinergic and adrenergic mechanisms in the mediation of cardiovascular responses to 5-HT in chicken.", "contents": "Cardiovascular tryptamine receptors in the chicken. The effects of \"M\"-receptor blockers (atropine and morphine), \"D\"-receptor blockers (dibenamine, dibenzyline, methysergide) and a ganglion blocking agent (mecamylamine) were studied to characterize cardiovascular tryptaminergic receptors in domestic fowl. This study showed the presence of both \"M\" and \"D\" tryptaminergic receptors (both mediating systemic hypotension) and also other \"D\"-receptors, which mediate arterial and venous hypertensive responses to 5-HT. There appear to be interactions of tryptaminergic, cholinergic and adrenergic mechanisms in the mediation of cardiovascular responses to 5-HT in chicken."} {"id": "PMID:1267538", "title": "Haemodynamic effects of adenosine-5'-carboxylic acid-amide in the anaesthetized dog during normal respiration and hypercapnic acidosis.", "content": "Adenosine-5'-carboxylic acid-amide (1 mug/kg/min) and adenosine (500 mug/kg/min), given in a 10-min infusion to anaesthetized dogs, produced qualitatively and quantitatively comparable cardiovascular effects, namely a marked increase in coronary blood flow and a generalized vasodilation, concomitantly with an increase in heart rate, left ventricular dp/dt, heart work, myocardial oxygen consumption, and pulmonary blood pressure; the pulmonary vascular resistance remained unchanged. Hypercapnic acidosis enhanced the coronary dilator effect of both compounds. These results indicate that adenosine and adenosine-5'-carboxylic acid-amide act at the same receptor sites.", "contents": "Haemodynamic effects of adenosine-5'-carboxylic acid-amide in the anaesthetized dog during normal respiration and hypercapnic acidosis. Adenosine-5'-carboxylic acid-amide (1 mug/kg/min) and adenosine (500 mug/kg/min), given in a 10-min infusion to anaesthetized dogs, produced qualitatively and quantitatively comparable cardiovascular effects, namely a marked increase in coronary blood flow and a generalized vasodilation, concomitantly with an increase in heart rate, left ventricular dp/dt, heart work, myocardial oxygen consumption, and pulmonary blood pressure; the pulmonary vascular resistance remained unchanged. Hypercapnic acidosis enhanced the coronary dilator effect of both compounds. These results indicate that adenosine and adenosine-5'-carboxylic acid-amide act at the same receptor sites."} {"id": "PMID:1267539", "title": "[Age dependent differences in the pharmacokinetics of furosemide in rats].", "content": "After i.p. administration of 0,60 mg/100 g of furosemide, adult rats excreted 50 to 70% of this diuretic drug unchanged and 10% as desfurylmethylfurosemide. The renal excretion of furosemide is slower in 5- and 15-day-old rats. Age differences in absorption from the abdominal cavity or in the reabsorption rate in the kidney tubules can be excluded. The excretion of furosemide by the kidney is competitively inhibited by p-aminohippuric acid (PAH). The relative small inhibitory effect of PAH in young rats is caused by a smaller participation of tubular secretion in the renal excretion of furosemide in this age group. The half life time of furosemide is 83 min in 5-day-old rats and 47 min in 55-day-old rats. The distribution volume is 146% of body weight in both age groups. The concentration of furosemide in the kidney homogenate is higher in young rats than in adults. The slow renal excretion of furosemide in young rats is in accordance with the prolonged efficacy. The greater efficacy of furosemide in 5- and 15-day-old rats than in adults is caused particularly by differences in the conditions for diuretic effectiveness, especially by the retention of water and electrolytes in young rats.", "contents": "[Age dependent differences in the pharmacokinetics of furosemide in rats]. After i.p. administration of 0,60 mg/100 g of furosemide, adult rats excreted 50 to 70% of this diuretic drug unchanged and 10% as desfurylmethylfurosemide. The renal excretion of furosemide is slower in 5- and 15-day-old rats. Age differences in absorption from the abdominal cavity or in the reabsorption rate in the kidney tubules can be excluded. The excretion of furosemide by the kidney is competitively inhibited by p-aminohippuric acid (PAH). The relative small inhibitory effect of PAH in young rats is caused by a smaller participation of tubular secretion in the renal excretion of furosemide in this age group. The half life time of furosemide is 83 min in 5-day-old rats and 47 min in 55-day-old rats. The distribution volume is 146% of body weight in both age groups. The concentration of furosemide in the kidney homogenate is higher in young rats than in adults. The slow renal excretion of furosemide in young rats is in accordance with the prolonged efficacy. The greater efficacy of furosemide in 5- and 15-day-old rats than in adults is caused particularly by differences in the conditions for diuretic effectiveness, especially by the retention of water and electrolytes in young rats."} {"id": "PMID:1267540", "title": "Interaction of angiotensin II with noradrenaline and other spasmogens on rabbit isolated aortic strips.", "content": "Angiotensin II in sub-contractor concentrations enhanced the contractions of rabbit isolated aortic strips to noradrenaline, potassium chloride, histamine, acetylcholine, isoprenaline and 5HT. The potentiation of noradrenaline responses by angiotensin II was independent of any effect of angiotensin II on neuronal uptake of noradrenaline. The sensitization of this tissue to spasmogens induced by angiotensin II occurred in reserpine-treated preparations and in normal tissues suspended in calcium-free bathing medium. Procedures which abolished the transfer of sodium ions across membranes such as substitution of fructose for glucose in the bathing medium, absence of potassium ions or treatment with ouabain each abolished the non-specific sensitization. The evidence suggests that angiotensin II may cause a non-specific sensitization of this tissue by inhibiting sodium transfer across the cell membrane.", "contents": "Interaction of angiotensin II with noradrenaline and other spasmogens on rabbit isolated aortic strips. Angiotensin II in sub-contractor concentrations enhanced the contractions of rabbit isolated aortic strips to noradrenaline, potassium chloride, histamine, acetylcholine, isoprenaline and 5HT. The potentiation of noradrenaline responses by angiotensin II was independent of any effect of angiotensin II on neuronal uptake of noradrenaline. The sensitization of this tissue to spasmogens induced by angiotensin II occurred in reserpine-treated preparations and in normal tissues suspended in calcium-free bathing medium. Procedures which abolished the transfer of sodium ions across membranes such as substitution of fructose for glucose in the bathing medium, absence of potassium ions or treatment with ouabain each abolished the non-specific sensitization. The evidence suggests that angiotensin II may cause a non-specific sensitization of this tissue by inhibiting sodium transfer across the cell membrane."} {"id": "PMID:1267541", "title": "Nature of the inhibition by amiodarone of isoproterenol-induced tachycardia in the dog.", "content": "Inhibition of in vivo isoproterenol-induced tachycardia by i.v. amiodarone was studied in anesthetized dogs. Significant dose-response curves to isoproterenol could not be obtained in single animals because of the time-dependent lowering of the inhibitory effect of the drug. Single isoproterenol injections after amiodarone in 105 dogs allowed dose-response curves to be obtained. The slope of these curves decreased with increasing doses of amiodarone, and the maximal rate stimulation diminished also in a dose-dependent manner. These features are consistent with a non-competitive inhibition pattern. A mechanism of the beta-adrenergic antagonism developed by amiodarone is suggested.", "contents": "Nature of the inhibition by amiodarone of isoproterenol-induced tachycardia in the dog. Inhibition of in vivo isoproterenol-induced tachycardia by i.v. amiodarone was studied in anesthetized dogs. Significant dose-response curves to isoproterenol could not be obtained in single animals because of the time-dependent lowering of the inhibitory effect of the drug. Single isoproterenol injections after amiodarone in 105 dogs allowed dose-response curves to be obtained. The slope of these curves decreased with increasing doses of amiodarone, and the maximal rate stimulation diminished also in a dose-dependent manner. These features are consistent with a non-competitive inhibition pattern. A mechanism of the beta-adrenergic antagonism developed by amiodarone is suggested."} {"id": "PMID:1267542", "title": "Cycrimine on rat diaphragm.", "content": "Cycrimine hydrochloride, an anti-Parkinson drug having central cholinolytic properties, was found to cause neuromuscular blockade in the isolated rat diaphragm preparation. The neuromuscular blockade by cycrimine remained unaffected in presence of neostigmine and tetraethylammonium. Lower concentrations of cycrimine potentiated the paralytic effect of d-tubocurarine. A similar paralytic effect of cycrimine was observed in the pharmacologically denervated rat diaphragm. Responses to acetylcholine administered by retrograde i.v. injection were found to be inhibited in presence of cycrimine. These results suggest that the neuromuscular blockade by cycrimine is produced by a postsynaptic direct effect on the muscle.", "contents": "Cycrimine on rat diaphragm. Cycrimine hydrochloride, an anti-Parkinson drug having central cholinolytic properties, was found to cause neuromuscular blockade in the isolated rat diaphragm preparation. The neuromuscular blockade by cycrimine remained unaffected in presence of neostigmine and tetraethylammonium. Lower concentrations of cycrimine potentiated the paralytic effect of d-tubocurarine. A similar paralytic effect of cycrimine was observed in the pharmacologically denervated rat diaphragm. Responses to acetylcholine administered by retrograde i.v. injection were found to be inhibited in presence of cycrimine. These results suggest that the neuromuscular blockade by cycrimine is produced by a postsynaptic direct effect on the muscle."} {"id": "PMID:1267543", "title": "Determination of endogenous concentrations of norepinephrine and dopamine and their rates of synthesis in a single mouse brain: biphasic effects of (+)-amphetamine.", "content": "A method is described that possesses sufficient sensitivity to permit the simultaneous fluorometric assay of endogenous concentrations of tyrosine, dopamine and norepinephrine, and the measurement of the estimated rate of synthesis of 3H-dopamine and 3H-norepinephrine from 3H-tyrosine in a single mouse brain. (+)-Amphetamine elicited a biphasic effect reducing the estimated rate of synthesis of dopamine and norepinephrine at 5 mg/kg, while lowering the endogenous concentrations of these catecholamines and increasing their rates of synthesis at 15 mg/kg.", "contents": "Determination of endogenous concentrations of norepinephrine and dopamine and their rates of synthesis in a single mouse brain: biphasic effects of (+)-amphetamine. A method is described that possesses sufficient sensitivity to permit the simultaneous fluorometric assay of endogenous concentrations of tyrosine, dopamine and norepinephrine, and the measurement of the estimated rate of synthesis of 3H-dopamine and 3H-norepinephrine from 3H-tyrosine in a single mouse brain. (+)-Amphetamine elicited a biphasic effect reducing the estimated rate of synthesis of dopamine and norepinephrine at 5 mg/kg, while lowering the endogenous concentrations of these catecholamines and increasing their rates of synthesis at 15 mg/kg."} {"id": "PMID:1267544", "title": "Inhibition by indomethacin and niflumic acid of catecholamine--uptake into rat hypothalamic and striatal synaptosomes.", "content": "Niflumic acid and indomethacin showed to be inhibitors of catecholamine--uptake into rat striatal and hypothalamic synaptosomes. Whereas the inhibition by niflumic acid was non-competitive for both amines at similar Ki values, the action of indomethacin displayed differences between areas as well as amines: the potency of inhibition by indomethacin was greater in striatal than in hypothalamic synaptosomes irrespective of the amine; the type of inhibition by indomethacin was non-competitive for norepinephrine, but competitive for dopamine regardless of the brain area.", "contents": "Inhibition by indomethacin and niflumic acid of catecholamine--uptake into rat hypothalamic and striatal synaptosomes. Niflumic acid and indomethacin showed to be inhibitors of catecholamine--uptake into rat striatal and hypothalamic synaptosomes. Whereas the inhibition by niflumic acid was non-competitive for both amines at similar Ki values, the action of indomethacin displayed differences between areas as well as amines: the potency of inhibition by indomethacin was greater in striatal than in hypothalamic synaptosomes irrespective of the amine; the type of inhibition by indomethacin was non-competitive for norepinephrine, but competitive for dopamine regardless of the brain area."} {"id": "PMID:1267545", "title": "Distribution and retention of exogenously administered alkali metal ions in the mouse brain.", "content": "A pharmacokinetic study of the distribution and retention profiles of Li+, Rb+ and Cs+ in the brain and blood was performed in male mice given single (acute) or repeated (semi-chronic) injections of the respective chloride salt solutions. The concentration of Li+ in whole brain and in cerebral cortex, striatum, hippocampus, diencephalon, brain stem and cerebellum were similar after acute and semichronic LiCl treatment. In contrast, semi-chronic RbCl and CsCl treatment resulted in greater accumulation of Rb+ and Cs+ in brain compared to the levels obtained after acute administration. The Li+ concentration in brain declined to negligible amounts at 48 hr after termination of acute or semi-chronic LiCl administration, while the Rb+ and Cs+ concentration in the brain remained elevated for up to 6 days after termination of semi-chronic treatment. Differences in the distribution and retention patterns of Li+, Rb+ and Cs+ also were observed in the brain regions examined. In the blood, the concentration of Li+ reached a peak soon after LiCl administration and then progressively declined while Rb+ and Cs+ concentrations showed a biphasic course with the highest levels obtained 48 hr after administration of the salt solutions. It is suggested that the differences observed in the pharmacokinetics of Li+ compared to Rb+ and Cs+ in the brain might be related to their duration of actions.", "contents": "Distribution and retention of exogenously administered alkali metal ions in the mouse brain. A pharmacokinetic study of the distribution and retention profiles of Li+, Rb+ and Cs+ in the brain and blood was performed in male mice given single (acute) or repeated (semi-chronic) injections of the respective chloride salt solutions. The concentration of Li+ in whole brain and in cerebral cortex, striatum, hippocampus, diencephalon, brain stem and cerebellum were similar after acute and semichronic LiCl treatment. In contrast, semi-chronic RbCl and CsCl treatment resulted in greater accumulation of Rb+ and Cs+ in brain compared to the levels obtained after acute administration. The Li+ concentration in brain declined to negligible amounts at 48 hr after termination of acute or semi-chronic LiCl administration, while the Rb+ and Cs+ concentration in the brain remained elevated for up to 6 days after termination of semi-chronic treatment. Differences in the distribution and retention patterns of Li+, Rb+ and Cs+ also were observed in the brain regions examined. In the blood, the concentration of Li+ reached a peak soon after LiCl administration and then progressively declined while Rb+ and Cs+ concentrations showed a biphasic course with the highest levels obtained 48 hr after administration of the salt solutions. It is suggested that the differences observed in the pharmacokinetics of Li+ compared to Rb+ and Cs+ in the brain might be related to their duration of actions."} {"id": "PMID:1267546", "title": "Physostigmine as a discriminative cue in rats.", "content": "Rats, trained to respond differentially in a T-maze contingent upon the presence or absence of physostigmine (0.50 mg/kg), showed a reversal of drug responding when physostigmine (0.50 mg/kg) was given simultaneously with the anticholinergic ditran (dose range: 0.80-3.20 mg/kg). Testing the quaternary anticholinesterase neostigmine (0.50 mg/kg) resulted in no drug responding which indicates a central site of action for the physostigmine discrimination.", "contents": "Physostigmine as a discriminative cue in rats. Rats, trained to respond differentially in a T-maze contingent upon the presence or absence of physostigmine (0.50 mg/kg), showed a reversal of drug responding when physostigmine (0.50 mg/kg) was given simultaneously with the anticholinergic ditran (dose range: 0.80-3.20 mg/kg). Testing the quaternary anticholinesterase neostigmine (0.50 mg/kg) resulted in no drug responding which indicates a central site of action for the physostigmine discrimination."} {"id": "PMID:1267547", "title": "Normalization of abnormal T waves in ischemia.", "content": "Inverted T waves due to coronary artery disease and previous myocardial infarction were observed to revert ot normal, upright position during ischemia in 38 patients. The normalization of inverted T waves was seen on the electroencephalograms of 19 patients during spontaneously occurring angina pectoris and of 11 patients when ischemia was provoked by treadmill exercise; for 8 patients, normalization occurred during the administration of isoproterenol hydrochloride and during the consequent episode of angina pectoris. The mechanism for normalization may be the algebraic sum of the extent of ST segment elevation and the amplitude of the T waves of acute ischemia plus the extent of preexisting ST segment depression and the degree of T wave inversion, to result in isoelectric ST segment and upright T wave. As with myocardial infarction, reciprocal changes may also be recorded. However, the reciprocal nature may be masked since either acute ST segment elevation of T wave inversion, or both, may not be recorded in the leads reflecting the ischemic area because of normalization.", "contents": "Normalization of abnormal T waves in ischemia. Inverted T waves due to coronary artery disease and previous myocardial infarction were observed to revert ot normal, upright position during ischemia in 38 patients. The normalization of inverted T waves was seen on the electroencephalograms of 19 patients during spontaneously occurring angina pectoris and of 11 patients when ischemia was provoked by treadmill exercise; for 8 patients, normalization occurred during the administration of isoproterenol hydrochloride and during the consequent episode of angina pectoris. The mechanism for normalization may be the algebraic sum of the extent of ST segment elevation and the amplitude of the T waves of acute ischemia plus the extent of preexisting ST segment depression and the degree of T wave inversion, to result in isoelectric ST segment and upright T wave. As with myocardial infarction, reciprocal changes may also be recorded. However, the reciprocal nature may be masked since either acute ST segment elevation of T wave inversion, or both, may not be recorded in the leads reflecting the ischemic area because of normalization."} {"id": "PMID:1267548", "title": "Prognosis of patients permanently paced for sick sinus syndrome.", "content": "In 39 patients (mean age, 66 years) treated for sick sinus syndrome (SSS) with pacemaker insertion, the long-term prognosis was studied. Fifteen patients (42%) died during the follow-up period of 6 to 59 months (mean, 25 months). Three patients were unavailable for follow-up. Eleven of the 15 deaths (73%) were cardiac-related, yet none could be associated with either an arrhythmia or pacemaker failure. Symptoms recurred or persisted after pacemaker insertion in 14 patients (mean age, 71 years), nine of whom died (31 deaths per 100 patient follow-up years). Twenty-two patients (mean age, 63 years) were asymptomatic after pacer insertion, six of whom died (11 deaths per 100 patient follow-up years). These follow-up results demonstrate a poor long-term prognosis in patients with SSS and persistent symptoms following permanent pacing.", "contents": "Prognosis of patients permanently paced for sick sinus syndrome. In 39 patients (mean age, 66 years) treated for sick sinus syndrome (SSS) with pacemaker insertion, the long-term prognosis was studied. Fifteen patients (42%) died during the follow-up period of 6 to 59 months (mean, 25 months). Three patients were unavailable for follow-up. Eleven of the 15 deaths (73%) were cardiac-related, yet none could be associated with either an arrhythmia or pacemaker failure. Symptoms recurred or persisted after pacemaker insertion in 14 patients (mean age, 71 years), nine of whom died (31 deaths per 100 patient follow-up years). Twenty-two patients (mean age, 63 years) were asymptomatic after pacer insertion, six of whom died (11 deaths per 100 patient follow-up years). These follow-up results demonstrate a poor long-term prognosis in patients with SSS and persistent symptoms following permanent pacing."} {"id": "PMID:1267549", "title": "Diabetes among men in a general population. Prevalence and associated physiological findings.", "content": "A random sample of 281 men, aged 30 through 69, resident in the community of Tecumseh, Mich, was studied with the use of standard glucose tolerance tests, including serum insulin assays and fasting serum lipid concentrations. Diagnoses of diabetes and probable diabetes were made according to a modification of the criteria of Fajans and Conn. Prevalence of diabetes and probable diabetes was considerably higher among men aged 40 through 49 than among those aged 30 through 39, but it increased little in the 50-through-59 and 60-through-69 age groups. Lean nondiabetics and probable diabetics had similar mean systolic blood pressures and similar mean levels of serum cholesterol, serum triglycerides, and serum insulin, but fat probable diabetics had much higher mean serum lipid and serum insulin concentrations that fat nondiabetics. Adiposity grouping discriminated by variable levels less well between diabetics and nondiabetics.", "contents": "Diabetes among men in a general population. Prevalence and associated physiological findings. A random sample of 281 men, aged 30 through 69, resident in the community of Tecumseh, Mich, was studied with the use of standard glucose tolerance tests, including serum insulin assays and fasting serum lipid concentrations. Diagnoses of diabetes and probable diabetes were made according to a modification of the criteria of Fajans and Conn. Prevalence of diabetes and probable diabetes was considerably higher among men aged 40 through 49 than among those aged 30 through 39, but it increased little in the 50-through-59 and 60-through-69 age groups. Lean nondiabetics and probable diabetics had similar mean systolic blood pressures and similar mean levels of serum cholesterol, serum triglycerides, and serum insulin, but fat probable diabetics had much higher mean serum lipid and serum insulin concentrations that fat nondiabetics. Adiposity grouping discriminated by variable levels less well between diabetics and nondiabetics."} {"id": "PMID:1267550", "title": "Elevated plasma MB creatine phosphokinase activity. A specific marker for myocardial infarction in perioperative patients.", "content": "Plasma MB creatine phosphokinase (CPK) activity is consistently elevated following myocardial infarction (MI). To determine whether elevations of plasma MB CPK activity is a specific index of myocardial injury, CPK and isoenzymes were assayed by a quantitative kinetic fluorometric technique in fresh organs obtained at surgery. Analysis of CPK isoenzymes showed myocardium to be essentially the only organ with MB CPK. Operative procedures included thoracic, neck, genitourinary, and orthopedic surgery. Total plasma CPK activity increased in all patients; however, MB CPK activity was not elevated. Thus, (1) the heart appears to be the only organ that is capable of liberating substantial amounts of MB CPK into plasma; (2) in spite of notably increased CPK activity after cardiac surgery, MB CPK activity is not elevated; and (3) increased MB CPK activity is a reliable index of MI in postoperative patients.", "contents": "Elevated plasma MB creatine phosphokinase activity. A specific marker for myocardial infarction in perioperative patients. Plasma MB creatine phosphokinase (CPK) activity is consistently elevated following myocardial infarction (MI). To determine whether elevations of plasma MB CPK activity is a specific index of myocardial injury, CPK and isoenzymes were assayed by a quantitative kinetic fluorometric technique in fresh organs obtained at surgery. Analysis of CPK isoenzymes showed myocardium to be essentially the only organ with MB CPK. Operative procedures included thoracic, neck, genitourinary, and orthopedic surgery. Total plasma CPK activity increased in all patients; however, MB CPK activity was not elevated. Thus, (1) the heart appears to be the only organ that is capable of liberating substantial amounts of MB CPK into plasma; (2) in spite of notably increased CPK activity after cardiac surgery, MB CPK activity is not elevated; and (3) increased MB CPK activity is a reliable index of MI in postoperative patients."} {"id": "PMID:1267551", "title": "Bone marrow scan evaluation of arthropathy in sickle cell disorders.", "content": "Twelve patients with sickle cell hemoglobinopathies and arthropathy were studied, using technetium Tc 99m sulfur colloid bone marrow scans. Eight of 12 had decreased marrow radionuclide activity adjacent to painful joints, suggestion obliteration of vessels supplying bone marrow. Four patients without marrow defects on scanning had causes other than infarction for their joint symptoms, viz, small fractures, postinfectious synovitis, degenerative arthritis, and osteochondromas. Roentgenograms never showed bony abnormalities in five patients with marrow infarctions, and, in three others, showed defects several months later than did the marrow scans. Bone marrow scans offer a sensitive and early diagnostic aid in sickle cell hemoglobinopathies with arthropathy.", "contents": "Bone marrow scan evaluation of arthropathy in sickle cell disorders. Twelve patients with sickle cell hemoglobinopathies and arthropathy were studied, using technetium Tc 99m sulfur colloid bone marrow scans. Eight of 12 had decreased marrow radionuclide activity adjacent to painful joints, suggestion obliteration of vessels supplying bone marrow. Four patients without marrow defects on scanning had causes other than infarction for their joint symptoms, viz, small fractures, postinfectious synovitis, degenerative arthritis, and osteochondromas. Roentgenograms never showed bony abnormalities in five patients with marrow infarctions, and, in three others, showed defects several months later than did the marrow scans. Bone marrow scans offer a sensitive and early diagnostic aid in sickle cell hemoglobinopathies with arthropathy."} {"id": "PMID:1267552", "title": "Cushing syndrome with cyclical edema and periodic secretion of corticosteroids.", "content": "A patient had a malignant carcinoid tumor of the lung. Cyclical edema was closely associated with periodic secretion of corticosteroids. Surgical excision of the tumor reversed the clinical and biochemical abnormalities.", "contents": "Cushing syndrome with cyclical edema and periodic secretion of corticosteroids. A patient had a malignant carcinoid tumor of the lung. Cyclical edema was closely associated with periodic secretion of corticosteroids. Surgical excision of the tumor reversed the clinical and biochemical abnormalities."} {"id": "PMID:1267553", "title": "Unexplained bronchopulmonary disease with inflammatory bowel disease.", "content": "Six patients developed severe, unexplained, chronic bronchopulmonary disease from 3 to 13 years after the onset of nonspecific inflammatory disease of the colon. All had chronic bronchitis, bronchiectasis was diagnosed in four, and an obstructive type of pulmonary dysfunction was noted in five. Four of the six, including the two with only chronic bronchitis, had no history of smoking. There was an initial correlation between the pulmonary symptoms and the intestinal disease, except in two patients who developed overt pulmonary disease following total proctocolectomy. The frequent occurence of extraintestinal lesions has suggested that ulcerative colitis and regional enteritis are systemic disorders. Chronic unexplained bronchopulmonary disease may be another infrequent complication in such patients.", "contents": "Unexplained bronchopulmonary disease with inflammatory bowel disease. Six patients developed severe, unexplained, chronic bronchopulmonary disease from 3 to 13 years after the onset of nonspecific inflammatory disease of the colon. All had chronic bronchitis, bronchiectasis was diagnosed in four, and an obstructive type of pulmonary dysfunction was noted in five. Four of the six, including the two with only chronic bronchitis, had no history of smoking. There was an initial correlation between the pulmonary symptoms and the intestinal disease, except in two patients who developed overt pulmonary disease following total proctocolectomy. The frequent occurence of extraintestinal lesions has suggested that ulcerative colitis and regional enteritis are systemic disorders. Chronic unexplained bronchopulmonary disease may be another infrequent complication in such patients."} {"id": "PMID:1267554", "title": "Incomplete distal renal tubular acidosis in hypomagnesemia-dependent hypocalcemia.", "content": "The mechanism perpetuating hypocalcemia in the presence of hypomagnesemia is unknown. Two patients with this disorder had elevated immunoreactive serum parathyroid hormone levels and incomplete distal renal tubular acidosis. All abnormalities were corrected with magnesium replenishment. Postulated mechanisms include (1) parathyroid hormone activation in the serum or at the site of action dependent on magnesium, and (2) abnormalities in vitamin D metabolism that can be corrected by magnesium replacement.", "contents": "Incomplete distal renal tubular acidosis in hypomagnesemia-dependent hypocalcemia. The mechanism perpetuating hypocalcemia in the presence of hypomagnesemia is unknown. Two patients with this disorder had elevated immunoreactive serum parathyroid hormone levels and incomplete distal renal tubular acidosis. All abnormalities were corrected with magnesium replenishment. Postulated mechanisms include (1) parathyroid hormone activation in the serum or at the site of action dependent on magnesium, and (2) abnormalities in vitamin D metabolism that can be corrected by magnesium replacement."} {"id": "PMID:1267555", "title": "Reversal of systemic manifestations of cryoglobulinemia. Treatment with melphalan and prednisone.", "content": "In a patient with essential cryoglobulinemia with systemic, cutaneous, and neurologic manifestations and a mixed IgG-IgM cryoprotein, elimination of systemic and cutaneous disease manifestations, as well as notable reversal of neurologic impairment, followed therapy with melphalan. Levels of circulating cryoprotein decreased, but protein structure was unchanged by chemotherapy. Experience to date with alkylating agents suggests that this mode of treatment is the most effective currently available.", "contents": "Reversal of systemic manifestations of cryoglobulinemia. Treatment with melphalan and prednisone. In a patient with essential cryoglobulinemia with systemic, cutaneous, and neurologic manifestations and a mixed IgG-IgM cryoprotein, elimination of systemic and cutaneous disease manifestations, as well as notable reversal of neurologic impairment, followed therapy with melphalan. Levels of circulating cryoprotein decreased, but protein structure was unchanged by chemotherapy. Experience to date with alkylating agents suggests that this mode of treatment is the most effective currently available."} {"id": "PMID:1267556", "title": "Survival after asphyxia secondary to gravel aspiration.", "content": "A case of extreme asphyxia and acidemia secondary to mechanical obstruction of the tracheobronchial tree with sand and gravel is described. The roentgenographic appearance, clinical course, and management are emphasized. Survival with no neurologic sequelae after such profound physiologic disturbance has not, to our knowledge, previously been described.", "contents": "Survival after asphyxia secondary to gravel aspiration. A case of extreme asphyxia and acidemia secondary to mechanical obstruction of the tracheobronchial tree with sand and gravel is described. The roentgenographic appearance, clinical course, and management are emphasized. Survival with no neurologic sequelae after such profound physiologic disturbance has not, to our knowledge, previously been described."} {"id": "PMID:1267557", "title": "Combination antibiotic therapy in staphylococcal endocarditis. The use of methicillin sodium-gentamicin sulfate therapy.", "content": "The addition of gentamicin therapy in a case of S aureua endocarditis, in which the response to methicillin therapy alone was unsatisfactory, resulted in clinical improvement, enhanced serum bactericidal activity, and a bacteriologic cure. Gentamicin and methicillin were synergistic in vitro. Since the mortality in staphlococcal endocarditis remains exceedingly high, we suggest that the combination of a cell wall active antibiotic, such as methicillin, and an aminoglycoside may prove to be effective alternate theraphy for this disease.", "contents": "Combination antibiotic therapy in staphylococcal endocarditis. The use of methicillin sodium-gentamicin sulfate therapy. The addition of gentamicin therapy in a case of S aureua endocarditis, in which the response to methicillin therapy alone was unsatisfactory, resulted in clinical improvement, enhanced serum bactericidal activity, and a bacteriologic cure. Gentamicin and methicillin were synergistic in vitro. Since the mortality in staphlococcal endocarditis remains exceedingly high, we suggest that the combination of a cell wall active antibiotic, such as methicillin, and an aminoglycoside may prove to be effective alternate theraphy for this disease."} {"id": "PMID:1267558", "title": "Digital ischemia and gangrene preceding renal neoplasm. An association with sarcomatoid adenocarcinoma of the kidney.", "content": "A 63-year-old woman had acute onset of rapidly progressive Raynaud phenomenon and digital gangrene. Prior to the detection of a sarcomatoid renal carcinoma, prominemt hypergammaglobulinemia, microhematuria, and weight loss were noted. Following nephrectomy, the patient showed improvement of the Raynaud phenomenon, with complete healing of digital ulcers and decrease of gama-globulin levels. Immunofluroescence studies demonstrated substantial deposits of IgG that lined the tumor cells in a linear and diffuse pattern. Electron-dense deposits were seen in the endothelium of arterioles int the tumor by electron microscopy. These findings suggest that antibodies to tumor antigens may have participated in the induction of digital vasculitis and Raynaud phenomenon.", "contents": "Digital ischemia and gangrene preceding renal neoplasm. An association with sarcomatoid adenocarcinoma of the kidney. A 63-year-old woman had acute onset of rapidly progressive Raynaud phenomenon and digital gangrene. Prior to the detection of a sarcomatoid renal carcinoma, prominemt hypergammaglobulinemia, microhematuria, and weight loss were noted. Following nephrectomy, the patient showed improvement of the Raynaud phenomenon, with complete healing of digital ulcers and decrease of gama-globulin levels. Immunofluroescence studies demonstrated substantial deposits of IgG that lined the tumor cells in a linear and diffuse pattern. Electron-dense deposits were seen in the endothelium of arterioles int the tumor by electron microscopy. These findings suggest that antibodies to tumor antigens may have participated in the induction of digital vasculitis and Raynaud phenomenon."} {"id": "PMID:1267559", "title": "Factor IX deficiency in Gaucher disease. An in vitro phenomenon.", "content": "Low factor IX coagulant activity was demonstrated in a patient with Gaucher disease before and after splenectomy. The same abnormality was found in seven of ten additional patients studied. Possibly, abnormally retained sphingolipids inactivate or interfere with the action of certain procoagulants.", "contents": "Factor IX deficiency in Gaucher disease. An in vitro phenomenon. Low factor IX coagulant activity was demonstrated in a patient with Gaucher disease before and after splenectomy. The same abnormality was found in seven of ten additional patients studied. Possibly, abnormally retained sphingolipids inactivate or interfere with the action of certain procoagulants."} {"id": "PMID:1267569", "title": "Natural history of male psychological health. V. The relation of choice of ego mechanisms of defense to adult adjustment.", "content": "Ninety-five men, selected in college on the basis of health have been prospectively followed up for 30 years. Their adaptive styles have been isolated, labeled by the ego mechanisms of defense that their behavior reflects, and studied by semiquantitative techniques. A hierarchy of ego mechanisms was devised that ordered defenses along a continuum that reflected the following two dimensions: (1) immaturity-maturity and (2) psychopathology-mental health. The most important finding was that despite blind assessment, a scale reflecting the maturity of a subject's defenses correlated with scales measuring his objective psychopathology (r = -.35) and his objective adaptation to the external environment (r = .65). Highly significant shifts in defensive style occurred as individuals matured. In order to conceptualize the continuum that underlies mental health, identification of a person's dominant defensive styles may be superior to our current scheme of static unitary diagnoses.", "contents": "Natural history of male psychological health. V. The relation of choice of ego mechanisms of defense to adult adjustment. Ninety-five men, selected in college on the basis of health have been prospectively followed up for 30 years. Their adaptive styles have been isolated, labeled by the ego mechanisms of defense that their behavior reflects, and studied by semiquantitative techniques. A hierarchy of ego mechanisms was devised that ordered defenses along a continuum that reflected the following two dimensions: (1) immaturity-maturity and (2) psychopathology-mental health. The most important finding was that despite blind assessment, a scale reflecting the maturity of a subject's defenses correlated with scales measuring his objective psychopathology (r = -.35) and his objective adaptation to the external environment (r = .65). Highly significant shifts in defensive style occurred as individuals matured. In order to conceptualize the continuum that underlies mental health, identification of a person's dominant defensive styles may be superior to our current scheme of static unitary diagnoses."} {"id": "PMID:1267570", "title": "Losing a symptom through keeping it. A review of paradoxical treatment techniques and rationale.", "content": "The therapeutic technique of symptom prescription has been used by practitioners from a variety of clinical schools. This article reviews techniques based on learning theory, symptom redefinition, paradoxical intention, and directive therapy, among other approaches. A conceptual framework for understanding these various approaches is offered, utilizing data from psychoanalysis, learning theory, and interpersonal communication theory.", "contents": "Losing a symptom through keeping it. A review of paradoxical treatment techniques and rationale. The therapeutic technique of symptom prescription has been used by practitioners from a variety of clinical schools. This article reviews techniques based on learning theory, symptom redefinition, paradoxical intention, and directive therapy, among other approaches. A conceptual framework for understanding these various approaches is offered, utilizing data from psychoanalysis, learning theory, and interpersonal communication theory."} {"id": "PMID:1267571", "title": "A comparison of process notes and tape recordings. Implications for therapy research.", "content": "The basic contention of many researchers is that process notes are not suitable for objective study of psychotherapy. We focus here on our contrasting assumption that process notes may be effectively used for certain kinds of psychotherapy research, particularly that which deals with thematic shifts occurring over a period of time. To test this, three classes of taped memories were examined for thematic shifts: memories of the patient's father, mother, and repetitive memories. The taped memories were then compared with the memories recorded in the analyst's notes. Compared to the tapes, process note memories were fewer in number, significantly condensed, and introduced a variety of distortions into the data. In spite of these differences, judgments by independent raters indicated that in all three classes of memories, the analyst's notes reliably picked up pertinent thematic shifts.", "contents": "A comparison of process notes and tape recordings. Implications for therapy research. The basic contention of many researchers is that process notes are not suitable for objective study of psychotherapy. We focus here on our contrasting assumption that process notes may be effectively used for certain kinds of psychotherapy research, particularly that which deals with thematic shifts occurring over a period of time. To test this, three classes of taped memories were examined for thematic shifts: memories of the patient's father, mother, and repetitive memories. The taped memories were then compared with the memories recorded in the analyst's notes. Compared to the tapes, process note memories were fewer in number, significantly condensed, and introduced a variety of distortions into the data. In spite of these differences, judgments by independent raters indicated that in all three classes of memories, the analyst's notes reliably picked up pertinent thematic shifts."} {"id": "PMID:1267572", "title": "Appropriate and background affect in facial displays of emotion. Comparison of normal and schizophrenic males.", "content": "The hypothesis that normal subjects can express emotions more accurately than schizophrenics was tested by having judges match photographs of five posed affects with five emotion words for each of 16 normal and 16 schizophrenic male expressors. Discrimination accuracy was high, but the hypothesis was not confirmed. The results of a second study, in which separate measures of appropriate (intended) and \"background\" affect (eg, the rated intensity of anger displayed in a subject's nonangry poses) were provided, supported our expectation that discrimination accuracy is a function of both appropriate and background affect. The normal men tended to display more appropriate affect generally, and displayed more background happiness, while the schizophrenics expressed more background anger, sadness, and fear. Both intended and background affect, therefore, must be carefully considered in studies of emotional expressions.", "contents": "Appropriate and background affect in facial displays of emotion. Comparison of normal and schizophrenic males. The hypothesis that normal subjects can express emotions more accurately than schizophrenics was tested by having judges match photographs of five posed affects with five emotion words for each of 16 normal and 16 schizophrenic male expressors. Discrimination accuracy was high, but the hypothesis was not confirmed. The results of a second study, in which separate measures of appropriate (intended) and \"background\" affect (eg, the rated intensity of anger displayed in a subject's nonangry poses) were provided, supported our expectation that discrimination accuracy is a function of both appropriate and background affect. The normal men tended to display more appropriate affect generally, and displayed more background happiness, while the schizophrenics expressed more background anger, sadness, and fear. Both intended and background affect, therefore, must be carefully considered in studies of emotional expressions."} {"id": "PMID:1267573", "title": "Reactive psychoses and schizophrenia with good prognosis.", "content": "Cross-national studies have indicated that American psychiatrists diagnose schizophrenia more often than others. Clinical, genetic, and follow-up studies suggest that many patients diagnosed as having acute schizophrenia might be more appropriately diagnosed as having affective disorder. Forty probands diagnosed in Aarhus, Denmark, as having reactive psychoses are compared with 28 probands diagnosed in St Louis as having schizophrenia with good prognosis. Clinical differences largely reflect diagnostic criteria, with the patients from the St Louis group frequently having diagnosable affective disorder. A smaller proportion, 39% of the patients from St Louis, could be considered for the diagnosis of reactive psychosis. This is additional evidence supporting the use of the diagnostic category, reactive psychoses. Patients ordinarily given the diagnoses acute schizophrenic episode and/or schizo-affective schizophrenia may be more appropriately diagnosed as having (1) affective disorder and (2) reactive psychoses.", "contents": "Reactive psychoses and schizophrenia with good prognosis. Cross-national studies have indicated that American psychiatrists diagnose schizophrenia more often than others. Clinical, genetic, and follow-up studies suggest that many patients diagnosed as having acute schizophrenia might be more appropriately diagnosed as having affective disorder. Forty probands diagnosed in Aarhus, Denmark, as having reactive psychoses are compared with 28 probands diagnosed in St Louis as having schizophrenia with good prognosis. Clinical differences largely reflect diagnostic criteria, with the patients from the St Louis group frequently having diagnosable affective disorder. A smaller proportion, 39% of the patients from St Louis, could be considered for the diagnosis of reactive psychosis. This is additional evidence supporting the use of the diagnostic category, reactive psychoses. Patients ordinarily given the diagnoses acute schizophrenic episode and/or schizo-affective schizophrenia may be more appropriately diagnosed as having (1) affective disorder and (2) reactive psychoses."} {"id": "PMID:1267574", "title": "Catatonia. A prospective clinical study.", "content": "We studied 55 patients admitted during 14 months to two inpatient psychiatric units of a municipal hospital who exhibited one or more of the catatonic signs of mutism, stereotypy, posturing, catalepsy, automatic obedience, negativism, echolalia/echopraxia, or stupor. Only four of the 55 patients satisfied our research criteria for schizophrenia, whereas over two thirds had diagnosable affective disorders, usually mania. The eight catatonic motor signs were nonspecific and homogeneously distributed among the various research diagnostic groups, with the number and type of individual signs unrelated to short-term treatment outcome. A favorable treatment response was shown for the entire catatonic sample, with two thirds markedly improved or in remission at the time of discharge. These findings are consistent with those of other investigators of the catatonic syndrome for the past 100 years.", "contents": "Catatonia. A prospective clinical study. We studied 55 patients admitted during 14 months to two inpatient psychiatric units of a municipal hospital who exhibited one or more of the catatonic signs of mutism, stereotypy, posturing, catalepsy, automatic obedience, negativism, echolalia/echopraxia, or stupor. Only four of the 55 patients satisfied our research criteria for schizophrenia, whereas over two thirds had diagnosable affective disorders, usually mania. The eight catatonic motor signs were nonspecific and homogeneously distributed among the various research diagnostic groups, with the number and type of individual signs unrelated to short-term treatment outcome. A favorable treatment response was shown for the entire catatonic sample, with two thirds markedly improved or in remission at the time of discharge. These findings are consistent with those of other investigators of the catatonic syndrome for the past 100 years."} {"id": "PMID:1267575", "title": "Serum dopamine-beta-hydroxylase activity in the affective psychoses and schizophrenia. Decreased activity in unipolar psychotically depressed patients.", "content": "Serum dopamine-beta-hydroxylase (DBH) activity was studied in 125 psychiatric patients and 73 normal controls. Serum DBH activity in schizophrenic, bipolar manic, and neurotic depressive patients was not significantly different from that in controls. Although serum DBH activity in unipolar and bipolar depressed patients was also not significantly different from that in controls, the subgroup of psychotically depressed unipolar patients had significantly lower serum DBH levels than controls did. Serum DBH activity in bipolar psychotically depressed patients also tended to be low, but was not significantly less than in controls. Serum DBH activity in the patient group usually did not increase in the immediate period following successful treatment with drugs or electroconvulsive therapy, indicating that basal levels of serum DBH activity in psychiatric patients are not state-dependent. Low serum DBH levels in psychotically depressed patients must be verified in an independent group of patients before its significance can be appreciated. Our findings could be the result of the study of an atypical group of psychotically depressed patients.", "contents": "Serum dopamine-beta-hydroxylase activity in the affective psychoses and schizophrenia. Decreased activity in unipolar psychotically depressed patients. Serum dopamine-beta-hydroxylase (DBH) activity was studied in 125 psychiatric patients and 73 normal controls. Serum DBH activity in schizophrenic, bipolar manic, and neurotic depressive patients was not significantly different from that in controls. Although serum DBH activity in unipolar and bipolar depressed patients was also not significantly different from that in controls, the subgroup of psychotically depressed unipolar patients had significantly lower serum DBH levels than controls did. Serum DBH activity in bipolar psychotically depressed patients also tended to be low, but was not significantly less than in controls. Serum DBH activity in the patient group usually did not increase in the immediate period following successful treatment with drugs or electroconvulsive therapy, indicating that basal levels of serum DBH activity in psychiatric patients are not state-dependent. Low serum DBH levels in psychotically depressed patients must be verified in an independent group of patients before its significance can be appreciated. Our findings could be the result of the study of an atypical group of psychotically depressed patients."} {"id": "PMID:1267576", "title": "Klinefelter syndrome in a military population. Electroencephalographic, endocrine, and psychiatric status.", "content": "In a study of nine Klinefelter syndrome patients obtained from a military population, all were found to have normal electroencephalograms (EEGs), all were clinically euthyroid, and had normal thyroid function test results. All had normal verbal and nonverbal IQs and no evidence of neurologic dysfunction on psychological testing. There was a high incidence of personality maladjustment as indicated by both the Minnesota Multiphasic Personality inventory and individual psychiatric evaluation. No particular personality pattern appeared typical for the group as a whole. Neurologic dysfunction, as manifest by EEG abnormality, mental retardation, or neuropsychological test deficits, and hypothyroidism are not necessarily associated with Klinefelter syndrome. Likewise, although the incidence of personality disorders may be strongly associated with this disorder, no specific personality type appears especially characteristic of the syndrome.", "contents": "Klinefelter syndrome in a military population. Electroencephalographic, endocrine, and psychiatric status. In a study of nine Klinefelter syndrome patients obtained from a military population, all were found to have normal electroencephalograms (EEGs), all were clinically euthyroid, and had normal thyroid function test results. All had normal verbal and nonverbal IQs and no evidence of neurologic dysfunction on psychological testing. There was a high incidence of personality maladjustment as indicated by both the Minnesota Multiphasic Personality inventory and individual psychiatric evaluation. No particular personality pattern appeared typical for the group as a whole. Neurologic dysfunction, as manifest by EEG abnormality, mental retardation, or neuropsychological test deficits, and hypothyroidism are not necessarily associated with Klinefelter syndrome. Likewise, although the incidence of personality disorders may be strongly associated with this disorder, no specific personality type appears especially characteristic of the syndrome."} {"id": "PMID:1267577", "title": "Further studies on sex hormones in male homosexuals.", "content": "Plasma estrone, dihydrotestosterone, luteinizing hormone (LH), and percentage-free testosterone levels were determined in 26 predominantly or exclusively homosexual males (20 to 33 years of age) and in an age-matched control group. Although the homosexual and control groups showed a broad overlapping for all hormonal factors measured, highly significant differences between the groups were found without exception. The medians of the homosexual group (control group) and the significance levels for the two-sample rank tests were as follows: estrone 3.07 (2.43) ng/100 ml, P less than .01; dihydrotestosterone 66.0 (49.2) ng/100 ml, P less than .01; percentage-free testosterone 10.7% (9.7%), P less than .02; LH 35.1 (24.9) ng/ml, P less than .001. These findings can in part be explained by the higher LH secretion in the homosexual subjects.", "contents": "Further studies on sex hormones in male homosexuals. Plasma estrone, dihydrotestosterone, luteinizing hormone (LH), and percentage-free testosterone levels were determined in 26 predominantly or exclusively homosexual males (20 to 33 years of age) and in an age-matched control group. Although the homosexual and control groups showed a broad overlapping for all hormonal factors measured, highly significant differences between the groups were found without exception. The medians of the homosexual group (control group) and the significance levels for the two-sample rank tests were as follows: estrone 3.07 (2.43) ng/100 ml, P less than .01; dihydrotestosterone 66.0 (49.2) ng/100 ml, P less than .01; percentage-free testosterone 10.7% (9.7%), P less than .02; LH 35.1 (24.9) ng/ml, P less than .001. These findings can in part be explained by the higher LH secretion in the homosexual subjects."} {"id": "PMID:1267578", "title": "Effects of sleep deprivation on mood and central amine metabolism in depressed patients.", "content": "Nineteen patients, each hospitalized with a major depressive episode, were deprived of sleep for one night. Ten patients responded with clear improvement in depressive symptoms; the substantial clinical change was transient, usually lasting one day. Those who responded had significantly higher initial depression ratings (P less than .01) and tended to be older than nonresponders who experienced mild increases in irritability, fatigue, and discomfort following sleep deprivation. Amine metabolites, 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were not substantially affected by sleep deprivation, although there was a significant interaction of clinical response and direction of 3-methoxy-4-hydroxyphenylglycol (MHPG) change. Sleep deprivation thus produces acute, but only transient improvement in a selected group of severely depressed patients; it appears to be an important tool in the study of the affective disorders.", "contents": "Effects of sleep deprivation on mood and central amine metabolism in depressed patients. Nineteen patients, each hospitalized with a major depressive episode, were deprived of sleep for one night. Ten patients responded with clear improvement in depressive symptoms; the substantial clinical change was transient, usually lasting one day. Those who responded had significantly higher initial depression ratings (P less than .01) and tended to be older than nonresponders who experienced mild increases in irritability, fatigue, and discomfort following sleep deprivation. Amine metabolites, 5-hydroxyindoleacetic acid (5HIAA), and homovanillic acid (HVA) were not substantially affected by sleep deprivation, although there was a significant interaction of clinical response and direction of 3-methoxy-4-hydroxyphenylglycol (MHPG) change. Sleep deprivation thus produces acute, but only transient improvement in a selected group of severely depressed patients; it appears to be an important tool in the study of the affective disorders."} {"id": "PMID:1267579", "title": "Needle electromyography: its effect on serum creatine phosphokinase activity.", "content": "The effect of needle electromyography on serum creatine phosphokinase (CPK) levels has remained unclear despite the diagnostic implications. Serum CPK was serially assayed for changes before and after electromyography (EMG) in two healthy persons and ten persons having low back pain, while they remained at total bed rest. Mean curves showed a peak at 6 hours post-EMG and a return to baseline 48 hours post-EMG. The mean peak value was 1.5 times the baseline. Only one sample exceeded the normal range and it was from a patient with frank positive waves and fibrillation potentials. Correcting for dilution of CPK released, by body weight and for total trauma, by number of needle insertions did not modify the results. The time course and magnitude of elevation of CPK parallel those reported for post exercise changes but are much less than those reported to follow myocardial infarction. In the differential diagnosis of myopathies, care must be taken to ensure that the combination of needle electromyography, exercise, diurnal variation and active denervation does not lead to a \"false-positive\" elevation of CPK above the normal range. Needle electromyography by itself should not induce a false-positive CPK level in a normal person and no significant changes in CPK levels are likely to occur within two hours after the study.", "contents": "Needle electromyography: its effect on serum creatine phosphokinase activity. The effect of needle electromyography on serum creatine phosphokinase (CPK) levels has remained unclear despite the diagnostic implications. Serum CPK was serially assayed for changes before and after electromyography (EMG) in two healthy persons and ten persons having low back pain, while they remained at total bed rest. Mean curves showed a peak at 6 hours post-EMG and a return to baseline 48 hours post-EMG. The mean peak value was 1.5 times the baseline. Only one sample exceeded the normal range and it was from a patient with frank positive waves and fibrillation potentials. Correcting for dilution of CPK released, by body weight and for total trauma, by number of needle insertions did not modify the results. The time course and magnitude of elevation of CPK parallel those reported for post exercise changes but are much less than those reported to follow myocardial infarction. In the differential diagnosis of myopathies, care must be taken to ensure that the combination of needle electromyography, exercise, diurnal variation and active denervation does not lead to a \"false-positive\" elevation of CPK above the normal range. Needle electromyography by itself should not induce a false-positive CPK level in a normal person and no significant changes in CPK levels are likely to occur within two hours after the study."} {"id": "PMID:1267580", "title": "Spontaneous potentials in premature and full-term infants.", "content": "Spontaneous potentials may be normally found in the electromyograms of premature and full-term infants. These potentials tend to disappear as the infants mature past three months of age. However, in some infants with cerebral or metabolic disorders these spontaneous potentials may persist. Their pathogenesis is obscure. The electromyographer must be aware of their existence in disorders unrelated to the lower motor neuron.", "contents": "Spontaneous potentials in premature and full-term infants. Spontaneous potentials may be normally found in the electromyograms of premature and full-term infants. These potentials tend to disappear as the infants mature past three months of age. However, in some infants with cerebral or metabolic disorders these spontaneous potentials may persist. Their pathogenesis is obscure. The electromyographer must be aware of their existence in disorders unrelated to the lower motor neuron."} {"id": "PMID:1267581", "title": "Heat and stretch procedures: an evaluation using rat tail tendon.", "content": "This study evaluated various methods of applying force to collagenous tissue at various temperatures to produce permanent elongation, using rat tail tendon as the tissue model. A materials testing machine was used to measure the forces applied and the resulting elongation produced by differing procedures. Short-term vigorous stretching and prolonged moderate stretching were compared at 37 C. The effect of heating tissue prior to applying force was evaluated, and the effect of using a prolonged application of low force was demonstrated. The data showed that the low force, long duration procedure was very effective at producing residual elongation. Elevating tissue temperature and maintaining it prior to applying force was found to cause significantly less damage; and finally, the lower loads applied at elevated temperatures for prolonged periods were found to produce significantly greater residual elongation.", "contents": "Heat and stretch procedures: an evaluation using rat tail tendon. This study evaluated various methods of applying force to collagenous tissue at various temperatures to produce permanent elongation, using rat tail tendon as the tissue model. A materials testing machine was used to measure the forces applied and the resulting elongation produced by differing procedures. Short-term vigorous stretching and prolonged moderate stretching were compared at 37 C. The effect of heating tissue prior to applying force was evaluated, and the effect of using a prolonged application of low force was demonstrated. The data showed that the low force, long duration procedure was very effective at producing residual elongation. Elevating tissue temperature and maintaining it prior to applying force was found to cause significantly less damage; and finally, the lower loads applied at elevated temperatures for prolonged periods were found to produce significantly greater residual elongation."} {"id": "PMID:1267582", "title": "Heat stress: comparison of short exposure to severe dry and wet heat in saunas.", "content": "Sixty subjects, 33 males and 27 females, from 18 to 63 years of age, were exposed to two kinds of saunas: the Finnish sauna (dry sauna) with an air temperature of 80 to 90 C and a relative humidity of 50%, and the wet sauna with an air temperature of 45 to 50 C and a relative humidity of 100%. There was a rest period of one week between the two experiments. For the 60 subjects the mean duration in the wet sauna was 19.6 minutes and in the dry sauna it was 17.4 minutes. After 10 and 20 minutes of exposure in the wet sauna the mean rectal temperature was 38.1 and 38.5 respectively, the mean skin temperature 40.2 and 40.4 C, the respiratory rate 21 and 22.9 breaths/min, the pulse rate 113 and 135.4 beats/min, the mean diastolic pressure 76.1 and 71.9 mm Hg, and the mean systolic pressure 115.7 and 123.5 mm Hg. Comparing the different physiological parameters in both saunas showed significant differences only during the first 10 minutes: a greater drop in diastolic blood pressure, a higher increase in systolic blood pressure, and a greater rise in pulse rate in the dry sauna. After 20 minutes there were no significant differences between any of the above parameters. It is concluded that the heat strain and hence the risk in both saunas are similar and exposure in either sauna exceeding 10 minutes may be dangerous.", "contents": "Heat stress: comparison of short exposure to severe dry and wet heat in saunas. Sixty subjects, 33 males and 27 females, from 18 to 63 years of age, were exposed to two kinds of saunas: the Finnish sauna (dry sauna) with an air temperature of 80 to 90 C and a relative humidity of 50%, and the wet sauna with an air temperature of 45 to 50 C and a relative humidity of 100%. There was a rest period of one week between the two experiments. For the 60 subjects the mean duration in the wet sauna was 19.6 minutes and in the dry sauna it was 17.4 minutes. After 10 and 20 minutes of exposure in the wet sauna the mean rectal temperature was 38.1 and 38.5 respectively, the mean skin temperature 40.2 and 40.4 C, the respiratory rate 21 and 22.9 breaths/min, the pulse rate 113 and 135.4 beats/min, the mean diastolic pressure 76.1 and 71.9 mm Hg, and the mean systolic pressure 115.7 and 123.5 mm Hg. Comparing the different physiological parameters in both saunas showed significant differences only during the first 10 minutes: a greater drop in diastolic blood pressure, a higher increase in systolic blood pressure, and a greater rise in pulse rate in the dry sauna. After 20 minutes there were no significant differences between any of the above parameters. It is concluded that the heat strain and hence the risk in both saunas are similar and exposure in either sauna exceeding 10 minutes may be dangerous."} {"id": "PMID:1267583", "title": "Wheelchair cushions designed to prevent pressure sores: an evaluation.", "content": "Seven commercially available wheelchair cushions were tested for their ability to reduce reactive hyperemia in paralyzed patients. The cushions were evaluated daily for seven days on each of three patients. A Latin-square design was used to determine the sequence of evaluation on each of the days, and to control the effect of order of assessment. Patients sat on the cushions exactly 30 minutes after which the duration of any redness was measured with a stop watch. Before sitting on the next cushion, the patients remained off their buttocks for exactly 30 minutes. Data for the three patients were averaged, and an analysis of variance of the Latin-square showed no significant differences among the cushions.", "contents": "Wheelchair cushions designed to prevent pressure sores: an evaluation. Seven commercially available wheelchair cushions were tested for their ability to reduce reactive hyperemia in paralyzed patients. The cushions were evaluated daily for seven days on each of three patients. A Latin-square design was used to determine the sequence of evaluation on each of the days, and to control the effect of order of assessment. Patients sat on the cushions exactly 30 minutes after which the duration of any redness was measured with a stop watch. Before sitting on the next cushion, the patients remained off their buttocks for exactly 30 minutes. Data for the three patients were averaged, and an analysis of variance of the Latin-square showed no significant differences among the cushions."} {"id": "PMID:1267584", "title": "Sex education and counseling program on a spinal cord injury service.", "content": "A sex education and counseling program was designed for spinal cord-injured patients and their partners, and alternative approaches are briefly reviewed. Also notable is the importance of inservice training for staff working with the cord-injured.", "contents": "Sex education and counseling program on a spinal cord injury service. A sex education and counseling program was designed for spinal cord-injured patients and their partners, and alternative approaches are briefly reviewed. Also notable is the importance of inservice training for staff working with the cord-injured."} {"id": "PMID:1267586", "title": "Clinical applications of a standardized mobility test.", "content": "Four patients with mobility problems were evaluated in relation to their performances on a standardized mobility test throughout the course of their rehabilitation programs. While each of the four cases demonstrates the value of an objective measurement of independent function, each also reflects individual points of merit. Clinical application demonstrated the test's ability to separate out areas of mobility deficit, evaluate forms of treatment, and indicate need for follow-up. Further, the sensitivity of the test in long-term follow-up of mobility problems was illustrated.", "contents": "Clinical applications of a standardized mobility test. Four patients with mobility problems were evaluated in relation to their performances on a standardized mobility test throughout the course of their rehabilitation programs. While each of the four cases demonstrates the value of an objective measurement of independent function, each also reflects individual points of merit. Clinical application demonstrated the test's ability to separate out areas of mobility deficit, evaluate forms of treatment, and indicate need for follow-up. Further, the sensitivity of the test in long-term follow-up of mobility problems was illustrated."} {"id": "PMID:1267589", "title": "Graphical representation of neuromuscular function in spinal cord injury.", "content": "Accurate determination of the location and extent of a spinal cord leson is essential to the ongoing therapeutic plans for a patient as well as for overall program evaluation in a spinal cord center. The interpretation of muscle function tests performed for this purpose is often complex due to the large number of muscles innervated in part by a single segment of the cord and the overlapping pattern of innervation. The aggregation of the individual muscle ratings by spinal cord root segment and graphic presentation of this information provides a convenient means to gain an overview of muscle function and follow changes in the cord lesion over time through serial test results. Two cases demonstrate some of the graphic patterns that result from complete and incomplete lesions from shortly after injury with both receding and advancing involvement of the cord demonstrated.", "contents": "Graphical representation of neuromuscular function in spinal cord injury. Accurate determination of the location and extent of a spinal cord leson is essential to the ongoing therapeutic plans for a patient as well as for overall program evaluation in a spinal cord center. The interpretation of muscle function tests performed for this purpose is often complex due to the large number of muscles innervated in part by a single segment of the cord and the overlapping pattern of innervation. The aggregation of the individual muscle ratings by spinal cord root segment and graphic presentation of this information provides a convenient means to gain an overview of muscle function and follow changes in the cord lesion over time through serial test results. Two cases demonstrate some of the graphic patterns that result from complete and incomplete lesions from shortly after injury with both receding and advancing involvement of the cord demonstrated."} {"id": "PMID:1267590", "title": "Cerebral palsy: predictive value of selected clinical signs for early prognostication of motor function.", "content": "A prospective longitudinal study involving 233 children with cerebral palsy was carried out to select signs useful for early prognostication of ambulation. All patients were followed from the time they were 12 months old and their progress was observed until they reached the age of 3 to 11 years. The population consisted of 61 children having congenital hemiplegia, 37 having diplegia, 85 having spastic quadriparesis and 28 having the spastic-athetoid clinical type of cerebral palsy. In addition, there were 14 children with athetoid, 6 with ataxic and 2 with hypotonic cerebral palsy. Of the total population, 78.7% achieved some degree of functional walking. Findings indicated that the probability of ambulation was related to the clinical type of cerebral palsy. In some the ultimate functional outcome was rather uniform, as in those with congenital hemiplegic and ataxic types where the prognosis was consistently favorable or in those with hypotonic cerebral palsy in whom the outlook was poor. In spastic diplegic, quadriparetic, spastic-athetoid and athetoid types, on the other hand, expectations varied considerably. For this group of patients, sitting by two years was found to be a predictive sign of high reliability since all children who sat by this age eventually walked. For the group of patients not sitting by two years which included more than half of the eventual ambulators, suppression of obligatory primitive reflex activity between 18 and 24 months provided a sensitive indicator to distinguish the children who ultimately walked from those who would not be expected to do so. These data offer a possibility for predicting future ambulatory status by two years of age in those clinical types of cerebral palsy where difficulties of early accurate prognostication are most likely to be encountered. Observations also suggested that the presence of mental retardation adversely affects ambulation.", "contents": "Cerebral palsy: predictive value of selected clinical signs for early prognostication of motor function. A prospective longitudinal study involving 233 children with cerebral palsy was carried out to select signs useful for early prognostication of ambulation. All patients were followed from the time they were 12 months old and their progress was observed until they reached the age of 3 to 11 years. The population consisted of 61 children having congenital hemiplegia, 37 having diplegia, 85 having spastic quadriparesis and 28 having the spastic-athetoid clinical type of cerebral palsy. In addition, there were 14 children with athetoid, 6 with ataxic and 2 with hypotonic cerebral palsy. Of the total population, 78.7% achieved some degree of functional walking. Findings indicated that the probability of ambulation was related to the clinical type of cerebral palsy. In some the ultimate functional outcome was rather uniform, as in those with congenital hemiplegic and ataxic types where the prognosis was consistently favorable or in those with hypotonic cerebral palsy in whom the outlook was poor. In spastic diplegic, quadriparetic, spastic-athetoid and athetoid types, on the other hand, expectations varied considerably. For this group of patients, sitting by two years was found to be a predictive sign of high reliability since all children who sat by this age eventually walked. For the group of patients not sitting by two years which included more than half of the eventual ambulators, suppression of obligatory primitive reflex activity between 18 and 24 months provided a sensitive indicator to distinguish the children who ultimately walked from those who would not be expected to do so. These data offer a possibility for predicting future ambulatory status by two years of age in those clinical types of cerebral palsy where difficulties of early accurate prognostication are most likely to be encountered. Observations also suggested that the presence of mental retardation adversely affects ambulation."} {"id": "PMID:1267592", "title": "Abductor digiti quinti shuffleboard: a study in motor learning.", "content": "The purposes of this study were as follows: (1) to refine prior studies by investigating one muscle which provided all the agonistic motion involved in a novel motor task, (2) the pinpoint the exact time during which motor activity contributed to the final task, (3) to study the electrical changes that occurred in that one muscle as it developed skill, and (4) to compare the results of this study with the previous studies in this series. The muscle chosen for this study was the abductor digiti quinti of the nondominant hand and the novel task involved propelling a small plastic disk into a specific target area. Electromyography and cinematography were used in data collection. No statistically significant differences were found in prelearning and postlearning data with regard to electrical activity, movement time or range of movement. These results support a hypothesis earlier proposed by Payton to the effect that all the the agonists which contribute to a skilled performance begin as a relatively undifferentiated mass of muscle; as learning takes place the various elements of this muscle mass are differentiated into prime movers and auxiliaries. The electrical activity remains essentially the same in the prime movers while a marked reduction is seen in the auxiliary muscles. A reinterpretation of several earlier studies is suggested.", "contents": "Abductor digiti quinti shuffleboard: a study in motor learning. The purposes of this study were as follows: (1) to refine prior studies by investigating one muscle which provided all the agonistic motion involved in a novel motor task, (2) the pinpoint the exact time during which motor activity contributed to the final task, (3) to study the electrical changes that occurred in that one muscle as it developed skill, and (4) to compare the results of this study with the previous studies in this series. The muscle chosen for this study was the abductor digiti quinti of the nondominant hand and the novel task involved propelling a small plastic disk into a specific target area. Electromyography and cinematography were used in data collection. No statistically significant differences were found in prelearning and postlearning data with regard to electrical activity, movement time or range of movement. These results support a hypothesis earlier proposed by Payton to the effect that all the the agonists which contribute to a skilled performance begin as a relatively undifferentiated mass of muscle; as learning takes place the various elements of this muscle mass are differentiated into prime movers and auxiliaries. The electrical activity remains essentially the same in the prime movers while a marked reduction is seen in the auxiliary muscles. A reinterpretation of several earlier studies is suggested."} {"id": "PMID:1267593", "title": "Exercise effect on contractile properties of skeletal muscle in mouse muscular dystrophy.", "content": "The purpose of this study was to determine the effect of a high repetitive exercise program, treadmill running, on the tetanic tension and rate of tension development of the slow twitch soleus muscle of normal plus dystrophic mice and their littermates. The exercise program used would be considered to be of mild intensity since it failed to produce any detectable histochemical or biochemical changes. In the noninvolved normal and littermate mice, there was no difference in maximum tetanic tension between the exercised and nonexercised control groups. In the normal mice (eight weeks of age), there was a significant decrease in rate of tension development for those exercised for five weeks compared to nonexercised controls. In littermate mice (seven weeks old) exercised for a four-week period, there was also a significantly lower rate of tension development compared to their nonexercised controls. In dystrophic mice (seven weeks old) exercised for only one to two weeks, there was significantly lower tension as well as rate of tension developed for the exercised mice when compared to nonexercised dystrophic mice. In dystrophic mice (six weeks old) exercised for one to two weeks, there was no difference in tension or rate of tension development when compared to nonexercised controls. In both six and seven-week-old littermate mice, also exercised for one to two weeks, this reduction in tension and rate of tension development did not occur. The average life span for the dystrophic mice used in this study is about 30 weeks. Of the nine exercised dystrophic mice scheduled for study at eight weeks, only one survived, suggesting that even the mild exercise used might have shortened their life expectancy.", "contents": "Exercise effect on contractile properties of skeletal muscle in mouse muscular dystrophy. The purpose of this study was to determine the effect of a high repetitive exercise program, treadmill running, on the tetanic tension and rate of tension development of the slow twitch soleus muscle of normal plus dystrophic mice and their littermates. The exercise program used would be considered to be of mild intensity since it failed to produce any detectable histochemical or biochemical changes. In the noninvolved normal and littermate mice, there was no difference in maximum tetanic tension between the exercised and nonexercised control groups. In the normal mice (eight weeks of age), there was a significant decrease in rate of tension development for those exercised for five weeks compared to nonexercised controls. In littermate mice (seven weeks old) exercised for a four-week period, there was also a significantly lower rate of tension development compared to their nonexercised controls. In dystrophic mice (seven weeks old) exercised for only one to two weeks, there was significantly lower tension as well as rate of tension developed for the exercised mice when compared to nonexercised dystrophic mice. In dystrophic mice (six weeks old) exercised for one to two weeks, there was no difference in tension or rate of tension development when compared to nonexercised controls. In both six and seven-week-old littermate mice, also exercised for one to two weeks, this reduction in tension and rate of tension development did not occur. The average life span for the dystrophic mice used in this study is about 30 weeks. Of the nine exercised dystrophic mice scheduled for study at eight weeks, only one survived, suggesting that even the mild exercise used might have shortened their life expectancy."} {"id": "PMID:1267594", "title": "Longitudinal unobtrusive measurements in rehabilitation.", "content": "Most evaluation techniques in rehabilitation emphasize descriptions of patient capability during brief time intervals under relatively standardized conditions. This paper outlines a conceptual approach which emphasizes the importance of evaluating how patients actually perform under everyday circumstances during extended periods of time. The underlying strategy embodied in this approach consists of the following elements: (1) continuous monitoring of discrete activities over extended periods of time (hours to months); (2) data collection wherever the patient goes allowing nontest behavior patterns to be studied; and (3) unobtrusive, noninvasive, and ethically acceptable monitoring to minimize observer bias. Although numerous techniques can be used to obtain these kinds of measurements, recent advances in biomedical engineering make a technological approach both inexpensive and feasible for selected activities. In addition, unobtrusive instrumentation can help generate objective, quantitative information concerning actual patient behavior which provides a previously unavailable data base for evaluating individual patient progress, assessing program effectiveness and developing more relevant outcome measures. Two examples of studies which utilize longitudinal unobtrusive measurements are described and preliminary results are presented.", "contents": "Longitudinal unobtrusive measurements in rehabilitation. Most evaluation techniques in rehabilitation emphasize descriptions of patient capability during brief time intervals under relatively standardized conditions. This paper outlines a conceptual approach which emphasizes the importance of evaluating how patients actually perform under everyday circumstances during extended periods of time. The underlying strategy embodied in this approach consists of the following elements: (1) continuous monitoring of discrete activities over extended periods of time (hours to months); (2) data collection wherever the patient goes allowing nontest behavior patterns to be studied; and (3) unobtrusive, noninvasive, and ethically acceptable monitoring to minimize observer bias. Although numerous techniques can be used to obtain these kinds of measurements, recent advances in biomedical engineering make a technological approach both inexpensive and feasible for selected activities. In addition, unobtrusive instrumentation can help generate objective, quantitative information concerning actual patient behavior which provides a previously unavailable data base for evaluating individual patient progress, assessing program effectiveness and developing more relevant outcome measures. Two examples of studies which utilize longitudinal unobtrusive measurements are described and preliminary results are presented."} {"id": "PMID:1267599", "title": "Skoraya Pomosch: Emergency Medical Service of the Soviet Union.", "content": "The Emergency Medical Service of the Soviet Union as witnessed in 1975 shows evidence of central communication, organization, and planning. The Skoraya Pomosch has developed into an elite medical corps with general multispecialty emergency teams that include well-trained physicians and physicians' assistants, with emphasis on bringing medical care to the patient at the site of the emergency. At its optimum, it is an elite corps that is uniformly available and capable of response to minor emergencies as well as major community disasters. Chronic problems of inadequate equipment and inappropriate use of the system continue to plague the Skoraya as they do other aspects of Soviet medicine. Certain qualities, such as the central communication network, are probably adaptable to the United States' situation, but in general, we must continue to improve and devise our own emergency medical system.", "contents": "Skoraya Pomosch: Emergency Medical Service of the Soviet Union. The Emergency Medical Service of the Soviet Union as witnessed in 1975 shows evidence of central communication, organization, and planning. The Skoraya Pomosch has developed into an elite medical corps with general multispecialty emergency teams that include well-trained physicians and physicians' assistants, with emphasis on bringing medical care to the patient at the site of the emergency. At its optimum, it is an elite corps that is uniformly available and capable of response to minor emergencies as well as major community disasters. Chronic problems of inadequate equipment and inappropriate use of the system continue to plague the Skoraya as they do other aspects of Soviet medicine. Certain qualities, such as the central communication network, are probably adaptable to the United States' situation, but in general, we must continue to improve and devise our own emergency medical system."} {"id": "PMID:1267600", "title": "Crohn disease and pregnancy.", "content": "Seventy-eight women with Crohn disease, each having the physical capability and opportunity to bear children, were admitted to the New York Hospital-Cornell Medical Center during a 20-year period. Forty-two pregnancies occurred. Results are suggestive of overall decreased fertility with no significant difference according to site of disease. The outcome of the pregnancies was not unlike that of the general population. Pregnancy did not exert an adverse effect on the disease itself, but termination of pregnancy was associated with relapse of Crohn disease 24% of the time.", "contents": "Crohn disease and pregnancy. Seventy-eight women with Crohn disease, each having the physical capability and opportunity to bear children, were admitted to the New York Hospital-Cornell Medical Center during a 20-year period. Forty-two pregnancies occurred. Results are suggestive of overall decreased fertility with no significant difference according to site of disease. The outcome of the pregnancies was not unlike that of the general population. Pregnancy did not exert an adverse effect on the disease itself, but termination of pregnancy was associated with relapse of Crohn disease 24% of the time."} {"id": "PMID:1267601", "title": "Intercostal pulmonary hernia.", "content": "In five cases of intercostal pulmonary hernia, the hernia occurred following blunt chest trauma in two cases, after tube thoracostomy drainage in two, and following rib resection in one. Surgical repair was accomplished in three cases with good results, while in the remaining two the hernia underwent spontaneous regression.", "contents": "Intercostal pulmonary hernia. In five cases of intercostal pulmonary hernia, the hernia occurred following blunt chest trauma in two cases, after tube thoracostomy drainage in two, and following rib resection in one. Surgical repair was accomplished in three cases with good results, while in the remaining two the hernia underwent spontaneous regression."} {"id": "PMID:1267602", "title": "Basilar pneumonia simulating acute appendicitis in children.", "content": "Twelve children with acute abdominal pain, which was suspected of being acute appendicitis, were subsequently found to have lower lobe pneumonia. Diagnostic barium enema or operative exploration failed to demonstrate any appendiceal abnormality. The abdominal symptoms and the ileus subsided soon after the initiation of antibiotic therapy. Contrary to common belief, it was observed that left-sided pneumonia is capable of mimicking appendicitis almost as frequently as right-sided pneumonia. Since the likelihood of acute appendicitis accompanying pneumonia is small, operative intervention is rarely indicated and should be undertaken only after careful and intensive investigation.", "contents": "Basilar pneumonia simulating acute appendicitis in children. Twelve children with acute abdominal pain, which was suspected of being acute appendicitis, were subsequently found to have lower lobe pneumonia. Diagnostic barium enema or operative exploration failed to demonstrate any appendiceal abnormality. The abdominal symptoms and the ileus subsided soon after the initiation of antibiotic therapy. Contrary to common belief, it was observed that left-sided pneumonia is capable of mimicking appendicitis almost as frequently as right-sided pneumonia. Since the likelihood of acute appendicitis accompanying pneumonia is small, operative intervention is rarely indicated and should be undertaken only after careful and intensive investigation."} {"id": "PMID:1267603", "title": "Tracheal stenosis. A method of dilation with use of the fiberoptic bronchoscope.", "content": "Tracheal stenosis is not an uncommon sequel of prolonged endotracheal intubation. In some cases, immediate reconstruction is not feasible. We use the flexible fiberoptic bronchoscope and a lucent, tapered endotracheal tube for tracheal dilation. The fiberoptic bronchoscope is passed through a special T connector into the endotracheal tube and used to guide the tube under direct vision through the stricture.", "contents": "Tracheal stenosis. A method of dilation with use of the fiberoptic bronchoscope. Tracheal stenosis is not an uncommon sequel of prolonged endotracheal intubation. In some cases, immediate reconstruction is not feasible. We use the flexible fiberoptic bronchoscope and a lucent, tapered endotracheal tube for tracheal dilation. The fiberoptic bronchoscope is passed through a special T connector into the endotracheal tube and used to guide the tube under direct vision through the stricture."} {"id": "PMID:1267604", "title": "Peripheral nerve division for relentless ischemic foot pain.", "content": "During a three-year interval, 12 multisensory peripheral nerve divisions in ten patients were performed for intractable ischemic foot pain. The two major indications, after concluding that revascularization was impossible, were (1) the presence of localized, dry, and contained acral gangrene in patients who were not candidates for a lesser amputation and (2) patient or family refusal of a limb amputation.", "contents": "Peripheral nerve division for relentless ischemic foot pain. During a three-year interval, 12 multisensory peripheral nerve divisions in ten patients were performed for intractable ischemic foot pain. The two major indications, after concluding that revascularization was impossible, were (1) the presence of localized, dry, and contained acral gangrene in patients who were not candidates for a lesser amputation and (2) patient or family refusal of a limb amputation."} {"id": "PMID:1267605", "title": "Improvement in blood flow through a critical arterial stenosis by defibrination with ancrod.", "content": "Using electromagnetic flow probes, cardiac output and hind limb blood flow were measured in dogs in which one hind limb had been rendered ischemic. Four dogs served as controls; seven were defibrinated by intravenous infusion of ancrod, 1 unit/kg, over a 30-minute period. In both groups, hematocrit readings remained constant, but cardiac output fell (this was attributed to barbiturate anesthesia), as did flow in the normal hind limb. In the controls after three hours, flow in the ischemic hind limb had decreased by 34%, but in the treated animals it had increased by 20%. The difference was statistically significant (P less than .001). The selective increase in blood flow in the ischemic limb may be explained by the greater reduction in blood viscosity at low shear rates achieved by defibrination.", "contents": "Improvement in blood flow through a critical arterial stenosis by defibrination with ancrod. Using electromagnetic flow probes, cardiac output and hind limb blood flow were measured in dogs in which one hind limb had been rendered ischemic. Four dogs served as controls; seven were defibrinated by intravenous infusion of ancrod, 1 unit/kg, over a 30-minute period. In both groups, hematocrit readings remained constant, but cardiac output fell (this was attributed to barbiturate anesthesia), as did flow in the normal hind limb. In the controls after three hours, flow in the ischemic hind limb had decreased by 34%, but in the treated animals it had increased by 20%. The difference was statistically significant (P less than .001). The selective increase in blood flow in the ischemic limb may be explained by the greater reduction in blood viscosity at low shear rates achieved by defibrination."} {"id": "PMID:1267606", "title": "Direct injection into the gallbladder in dogs, using ultrasonic guidance.", "content": "Direct injection into the gallbladder can be accomplished with the guidance of the ultrasonic aspiration transducer. Possible bile peritonitis is a limiting factor, but not necessarily a complication that contraindicates the procedure. Some modifications of the procedure may be necessary, and further investigation into this potentially valuable procedure is indicated.", "contents": "Direct injection into the gallbladder in dogs, using ultrasonic guidance. Direct injection into the gallbladder can be accomplished with the guidance of the ultrasonic aspiration transducer. Possible bile peritonitis is a limiting factor, but not necessarily a complication that contraindicates the procedure. Some modifications of the procedure may be necessary, and further investigation into this potentially valuable procedure is indicated."} {"id": "PMID:1267607", "title": "Influence of enteral oxygen administration on the slow electrical activity of the intestine and stomach.", "content": "Thirty-eight starved cats, anesthetized with pentobarbital (Nembutal) sodium, received enteral administration of oxygen and other gases; the effect on intestinal motility as expressed by electrical activity was measured. Oxygen caused a notable increase in amplitude and frequency of slow electrical waves, while carbon dioxide and nitrogen caused no visible alterations. Phentolamine hydrochloride and propranolol hydrochloride together with atropine sulfate decreased the amplitude and frequency of oscillations to near zero; subsequent administration of enteral oxygen caused a notable increase in electrical activity, while enteral carbon dioxide produced no alterations. On the basis of our previous observations that enteral oxygen enhances oxygen and blood delivery to the gut wall, we suggest that the rise in stomach and intestinal electrical activity during enteral oxygen administration in conditions of surgical stress may be associated with an increase in oxygen and blood delivery to the gut wall.", "contents": "Influence of enteral oxygen administration on the slow electrical activity of the intestine and stomach. Thirty-eight starved cats, anesthetized with pentobarbital (Nembutal) sodium, received enteral administration of oxygen and other gases; the effect on intestinal motility as expressed by electrical activity was measured. Oxygen caused a notable increase in amplitude and frequency of slow electrical waves, while carbon dioxide and nitrogen caused no visible alterations. Phentolamine hydrochloride and propranolol hydrochloride together with atropine sulfate decreased the amplitude and frequency of oscillations to near zero; subsequent administration of enteral oxygen caused a notable increase in electrical activity, while enteral carbon dioxide produced no alterations. On the basis of our previous observations that enteral oxygen enhances oxygen and blood delivery to the gut wall, we suggest that the rise in stomach and intestinal electrical activity during enteral oxygen administration in conditions of surgical stress may be associated with an increase in oxygen and blood delivery to the gut wall."} {"id": "PMID:1267608", "title": "Manometric evaluation of an artificial intestinal valve.", "content": "A new type of intestinal valve was constructed by telescoping the proximal portion of the intestin into the distal portion. The length of telescoped intestine was expressed in relation to its diameter. Various lengths of intestine were tested in 29 dogs. Valvular function was evaluated under pentobarbital sodium anesthesia, with open-tip catheters perfused at a rate of 5 mul to 6 mul/sec. An intestinal valve, made by telescoping two diameter lengths of the intestine, yielded the most similar results manometrically to those of the ilecolonic junction. Mean isoperistaltic and antiperistaltic pressures were measured to be 25.0 +/- 2.0 and 39.0 +/- 3.8 cm H2O in the valve, and 20.4 +/- 2.2 and 39.7 +/- 5.1 cm H2O in the ileocolonic junction. No alteration of the valvular function was found in the long-term follow-up study.", "contents": "Manometric evaluation of an artificial intestinal valve. A new type of intestinal valve was constructed by telescoping the proximal portion of the intestin into the distal portion. The length of telescoped intestine was expressed in relation to its diameter. Various lengths of intestine were tested in 29 dogs. Valvular function was evaluated under pentobarbital sodium anesthesia, with open-tip catheters perfused at a rate of 5 mul to 6 mul/sec. An intestinal valve, made by telescoping two diameter lengths of the intestine, yielded the most similar results manometrically to those of the ilecolonic junction. Mean isoperistaltic and antiperistaltic pressures were measured to be 25.0 +/- 2.0 and 39.0 +/- 3.8 cm H2O in the valve, and 20.4 +/- 2.2 and 39.7 +/- 5.1 cm H2O in the ileocolonic junction. No alteration of the valvular function was found in the long-term follow-up study."} {"id": "PMID:1267609", "title": "Species differences in response to renal ischemia.", "content": "Different species appear to tolerate different amounts of renal ischemia. It is suggested that all kidneys are equally susceptible to ischemic damage, but that the whole animal response varies between species. Mice, rats, rabbits, and pigs were subjected to bilateral nephrectomy. Large animals had relatively smaller kidneys and survived longer than smaller animals. Therefore, the larger the animal, the more time available for recovery of a kidney damaged by ischemia. This adequately explains the apparent species differences in susceptibility to renal ischemia, which are only seen when the kidney is expected to support life immediately. Simple relationships are described, relating metabolic rate, body size, and survival time with no renal function.", "contents": "Species differences in response to renal ischemia. Different species appear to tolerate different amounts of renal ischemia. It is suggested that all kidneys are equally susceptible to ischemic damage, but that the whole animal response varies between species. Mice, rats, rabbits, and pigs were subjected to bilateral nephrectomy. Large animals had relatively smaller kidneys and survived longer than smaller animals. Therefore, the larger the animal, the more time available for recovery of a kidney damaged by ischemia. This adequately explains the apparent species differences in susceptibility to renal ischemia, which are only seen when the kidney is expected to support life immediately. Simple relationships are described, relating metabolic rate, body size, and survival time with no renal function."} {"id": "PMID:1267610", "title": "Obstructive jaundice and renal masses.", "content": "An 82-year-old patient with obstructive jaundice secondary to simple renal cyst also suffered pain and vomiting from partial duodenal obstruction. The symptoms were relieved by aspiration of 1,750 ml of fluid. This reaccumulated over a five-year period when aspiration again relieved his symptoms, which then only consisted of epigastric fullness. Review of the literature shows jaundice to be an extremely rare symptom of renal cyst.", "contents": "Obstructive jaundice and renal masses. An 82-year-old patient with obstructive jaundice secondary to simple renal cyst also suffered pain and vomiting from partial duodenal obstruction. The symptoms were relieved by aspiration of 1,750 ml of fluid. This reaccumulated over a five-year period when aspiration again relieved his symptoms, which then only consisted of epigastric fullness. Review of the literature shows jaundice to be an extremely rare symptom of renal cyst."} {"id": "PMID:1267611", "title": "Primary repair in transection of duodenum with avulsion of the common duct.", "content": "In combined pancreatoduodenal trauma, the surgeon usually chooses a diverting or resectional procedure at substantial risk. Simple closure of the duodenum and transposition of the common duct was accomplished at early operation in an 18-year-old boy who had almost complete transection of the duodenum with avulsion of the ampulia of Vater from blunt abdominal trauma. Transgastrojejunostomy and use of Chaffin tubes were discontinued prior to discharge from the hospital three weeks later. The postoperative course was complicated only by a brief pancreatitis. The excellent result persists more than two years later. In similar anatomic situations, consideration might be given to this operative approach.", "contents": "Primary repair in transection of duodenum with avulsion of the common duct. In combined pancreatoduodenal trauma, the surgeon usually chooses a diverting or resectional procedure at substantial risk. Simple closure of the duodenum and transposition of the common duct was accomplished at early operation in an 18-year-old boy who had almost complete transection of the duodenum with avulsion of the ampulia of Vater from blunt abdominal trauma. Transgastrojejunostomy and use of Chaffin tubes were discontinued prior to discharge from the hospital three weeks later. The postoperative course was complicated only by a brief pancreatitis. The excellent result persists more than two years later. In similar anatomic situations, consideration might be given to this operative approach."} {"id": "PMID:1267612", "title": "Pseudomembranous colitis treated with completely diverting ileostomy.", "content": "A seriously ill patient with pseudomembranous colitis of obscure origin responsed promptly to a completely diverting ileostomy. The ileostomy was successfully closed three months later when the colon appeared to be normal. In an unusually severe case of pseudomembranous colitis, where operation is required and where pseudomembranous colitis is the sole operative finding, a completely diverting ileostomy should be considered rather than a more extensive procedure.", "contents": "Pseudomembranous colitis treated with completely diverting ileostomy. A seriously ill patient with pseudomembranous colitis of obscure origin responsed promptly to a completely diverting ileostomy. The ileostomy was successfully closed three months later when the colon appeared to be normal. In an unusually severe case of pseudomembranous colitis, where operation is required and where pseudomembranous colitis is the sole operative finding, a completely diverting ileostomy should be considered rather than a more extensive procedure."} {"id": "PMID:1267613", "title": "Incomplete membranous obstruction of the inferior vena cava. Hemodynamic measurements and correction by balloon membranotomy and surgical resection.", "content": "This report discusses a patient with chronic liver disease and portal hypertension, initially thought to be caused by chronic bile duct obstruction or chronic hepatitis B. For evaluation of portal hypertension, hepatic vein catheterization was performed, disclosing incomplete membranous obstruction of the inferior vena cava at the level of the diaphragm--the probable cause of the liver disease. The obstruction was corrected by balloon membranotomy and surgical resection of the membrane. Hepatic vein catheterization in patients with chronic liver disease and portal hypertension allows detection of this lesion as well as evaluation of hepatic and portal hemodynamics.", "contents": "Incomplete membranous obstruction of the inferior vena cava. Hemodynamic measurements and correction by balloon membranotomy and surgical resection. This report discusses a patient with chronic liver disease and portal hypertension, initially thought to be caused by chronic bile duct obstruction or chronic hepatitis B. For evaluation of portal hypertension, hepatic vein catheterization was performed, disclosing incomplete membranous obstruction of the inferior vena cava at the level of the diaphragm--the probable cause of the liver disease. The obstruction was corrected by balloon membranotomy and surgical resection of the membrane. Hepatic vein catheterization in patients with chronic liver disease and portal hypertension allows detection of this lesion as well as evaluation of hepatic and portal hemodynamics."} {"id": "PMID:1267614", "title": "Ectopic pelvic spleen.", "content": "We are reporting the first, to our knowledge, ectopic pelvic spleen demonstrated preoperatively by means of a liver-spleen scan and a selective splenic arteriogram. Symptoms, consisting of crampy pain in the lower part of the abdomen exacerbated by standing or stooping, were relieved by splenectomy in this 19-year-old woman. Splenopexy, which has been advocated in the past, has no place in the management of this rare and interesting congenital variant. Laxity or failure of development of the phrenicosplenic and gastrosplenic ligaments is thought to account for the splenic descensus.", "contents": "Ectopic pelvic spleen. We are reporting the first, to our knowledge, ectopic pelvic spleen demonstrated preoperatively by means of a liver-spleen scan and a selective splenic arteriogram. Symptoms, consisting of crampy pain in the lower part of the abdomen exacerbated by standing or stooping, were relieved by splenectomy in this 19-year-old woman. Splenopexy, which has been advocated in the past, has no place in the management of this rare and interesting congenital variant. Laxity or failure of development of the phrenicosplenic and gastrosplenic ligaments is thought to account for the splenic descensus."} {"id": "PMID:1267615", "title": "A simple effective technique for performing intraoperative cholangiography.", "content": "This simple, effective technique for performing intraoperative cholangiography uses a smooth-tipped side port cannula that is easily threaded into the cystic duct. Performance of intraoperative cholangiography is expedited by this method and artifacts commonly produced during cholangiography are avoided.", "contents": "A simple effective technique for performing intraoperative cholangiography. This simple, effective technique for performing intraoperative cholangiography uses a smooth-tipped side port cannula that is easily threaded into the cystic duct. Performance of intraoperative cholangiography is expedited by this method and artifacts commonly produced during cholangiography are avoided."} {"id": "PMID:1267616", "title": "Spontaneous rupture of the spleen. An unusual complication of anticoagulant therapy.", "content": "A 44-year-old man, who had been taking warfarin sodium because of a previous myocardial infarct, suddenly developed abdominal pain and signs of peritoneal irritation, requiring exploratory laparotomy. The spleen was ruptured. There were not any systemic diseases nor antecedents of trauma that could be considered predisposing factors for the apparently spontaneous rupture of the spleen. The only abnormality recorded was an elevated prothrombin time. Thus, a coagulopathy produced by the anticoagulants appeared to be the only possible predisposing factor for his splenic rupture.", "contents": "Spontaneous rupture of the spleen. An unusual complication of anticoagulant therapy. A 44-year-old man, who had been taking warfarin sodium because of a previous myocardial infarct, suddenly developed abdominal pain and signs of peritoneal irritation, requiring exploratory laparotomy. The spleen was ruptured. There were not any systemic diseases nor antecedents of trauma that could be considered predisposing factors for the apparently spontaneous rupture of the spleen. The only abnormality recorded was an elevated prothrombin time. Thus, a coagulopathy produced by the anticoagulants appeared to be the only possible predisposing factor for his splenic rupture."} {"id": "PMID:1267619", "title": "The sink action of cerebrospinal fluid volume flow. Effect on brain water content.", "content": "Effects of changes in serum osmolarity on volume flow of fluid into the cerebral ventricles of cats were measured by ventriculocisternal perfusion with mock cerebrospinal fluid (CSF), mock CSF containing acetazolamide, or a 30 mOsm/liter sucrose solution. Serum osmolarity was altered by intravenous infusion of a sucrose solution ranging between 10 and 650 mOsm/liter changing volume flow. For all perfusion fluids, regression lines relating volume flow to infused solution osmolarity were parallel. After infusion of a 10 mOsm/liter solution, brain water content increased. One hour after infusion, volume flow returned to normal, although serum was still hypotonic. Gray matter water content was still elevated; white matter returned to normal. The results suggest that the source of increased volume flow is the brain, and that the CSF acts as a sink, limiting excess water accumulation during water intoxication.", "contents": "The sink action of cerebrospinal fluid volume flow. Effect on brain water content. Effects of changes in serum osmolarity on volume flow of fluid into the cerebral ventricles of cats were measured by ventriculocisternal perfusion with mock cerebrospinal fluid (CSF), mock CSF containing acetazolamide, or a 30 mOsm/liter sucrose solution. Serum osmolarity was altered by intravenous infusion of a sucrose solution ranging between 10 and 650 mOsm/liter changing volume flow. For all perfusion fluids, regression lines relating volume flow to infused solution osmolarity were parallel. After infusion of a 10 mOsm/liter solution, brain water content increased. One hour after infusion, volume flow returned to normal, although serum was still hypotonic. Gray matter water content was still elevated; white matter returned to normal. The results suggest that the source of increased volume flow is the brain, and that the CSF acts as a sink, limiting excess water accumulation during water intoxication."} {"id": "PMID:1267620", "title": "Interlaboratory variability in determination of plasma antiepileptic drug concentrations.", "content": "The usefulness of plasma antiepileptic drug concentrations in treatment of epilepsy has been established, and many laboratories provide this service. A \"blind\" survey utilizing pooled patient plasma samples was conducted among 197 laboratories in the United States and Canada to establish the interlaboratory reproducibility. Three \"patient specimens\" containing different amounts of phenobarbital, phenytoin (diphenylhydantoin), primidone, and ethosuximide were employed; 112 laboratories reported results within five weeks. The average cost for analyzing four drugs in a single sample was $43.27. Half of the laboratories reported results outside +/- 1 standard deviation of the mean of five reference laboratories. Wide interlaboratory variability must be considered by the practicing physician. Until certified antiepileptic drug standards in a biologic matrix are available from the National Bureau of Standards, a volunteer quality control program among laboratories is needed.", "contents": "Interlaboratory variability in determination of plasma antiepileptic drug concentrations. The usefulness of plasma antiepileptic drug concentrations in treatment of epilepsy has been established, and many laboratories provide this service. A \"blind\" survey utilizing pooled patient plasma samples was conducted among 197 laboratories in the United States and Canada to establish the interlaboratory reproducibility. Three \"patient specimens\" containing different amounts of phenobarbital, phenytoin (diphenylhydantoin), primidone, and ethosuximide were employed; 112 laboratories reported results within five weeks. The average cost for analyzing four drugs in a single sample was $43.27. Half of the laboratories reported results outside +/- 1 standard deviation of the mean of five reference laboratories. Wide interlaboratory variability must be considered by the practicing physician. Until certified antiepileptic drug standards in a biologic matrix are available from the National Bureau of Standards, a volunteer quality control program among laboratories is needed."} {"id": "PMID:1267621", "title": "Rapid regular respiration in unconscious patients.", "content": "Respiratory frequency has been studied by strain gauge and impedance pneumography in a group of unconscious patients suffering from a variety of medical conditions, and has been compared with breathing in control subjects during wakefulness and sleep. Seventeen of 25 comatose patients had breathing patterns amenable to computerized statistical analysis of respiratory rate which demonstrated abnormalities in all patients studied. Unconscious patients breathed more rapidly and regularly than controls. Rapidity of respiration was not consistently associated with any specific central nervous system lesion, and was usually accompanied by coexistent pulmonary disease. Increasing regularity of respiration correlated well with deepening of coma and accurately reflected ultimate outcome even when other clinical signs were unchanging.", "contents": "Rapid regular respiration in unconscious patients. Respiratory frequency has been studied by strain gauge and impedance pneumography in a group of unconscious patients suffering from a variety of medical conditions, and has been compared with breathing in control subjects during wakefulness and sleep. Seventeen of 25 comatose patients had breathing patterns amenable to computerized statistical analysis of respiratory rate which demonstrated abnormalities in all patients studied. Unconscious patients breathed more rapidly and regularly than controls. Rapidity of respiration was not consistently associated with any specific central nervous system lesion, and was usually accompanied by coexistent pulmonary disease. Increasing regularity of respiration correlated well with deepening of coma and accurately reflected ultimate outcome even when other clinical signs were unchanging."} {"id": "PMID:1267622", "title": "Experimental arthrogryposis caused by viral myopathy.", "content": "Immobilization of the embryo has been postulated to cause the joint deformities in arthrogryposis multiplex congenita (AMC). Experimental damage to the motor neurons or pharmacologic blockade of neuromuscular transmission has previously resulted in typical joint changes of AMC. In the present investigation, we have studied the effects of paralysis produced by a viral myopathy on joint development. Coxsackievirus A2 was injected intravenously into chick embryos on the seventh day of incubation. Within 48 hours, severe myositis and paralysis resulted. Electron microscopical and immunofluorescence techniques demonstrated virus in muscle cells. Within three to four days after infection, the muscle had virtually disappeared. Ankylosis of joints, corresponding to that seen in human AMC, occurred. This study shows that primary myopathy with paralysis can produce arthrogrypotic joint deformities. The possibility of a viral etiologic factor in some human cases of AMC should be considered.", "contents": "Experimental arthrogryposis caused by viral myopathy. Immobilization of the embryo has been postulated to cause the joint deformities in arthrogryposis multiplex congenita (AMC). Experimental damage to the motor neurons or pharmacologic blockade of neuromuscular transmission has previously resulted in typical joint changes of AMC. In the present investigation, we have studied the effects of paralysis produced by a viral myopathy on joint development. Coxsackievirus A2 was injected intravenously into chick embryos on the seventh day of incubation. Within 48 hours, severe myositis and paralysis resulted. Electron microscopical and immunofluorescence techniques demonstrated virus in muscle cells. Within three to four days after infection, the muscle had virtually disappeared. Ankylosis of joints, corresponding to that seen in human AMC, occurred. This study shows that primary myopathy with paralysis can produce arthrogrypotic joint deformities. The possibility of a viral etiologic factor in some human cases of AMC should be considered."} {"id": "PMID:1267623", "title": "Myoclonus in familial restless legs syndrome.", "content": "Eighteen members of a family were affected over a span of five generations with the restless legs syndrome, transmitted as an autosomal dominant trait. Ten patients had myoclonus. The propositus, a 57-year-old man, suffered from repeated, intense, asymmetric flexion jerks of the lower extremities, alternating with fidgeting and friction movements of the legs; all occurred at night prior to sleep and severely interfering with it. The patient's movements ceased with the onset of stage 1 sleep, while in his brother, the motor activity persisted in stages 1 and 2 of sleep.", "contents": "Myoclonus in familial restless legs syndrome. Eighteen members of a family were affected over a span of five generations with the restless legs syndrome, transmitted as an autosomal dominant trait. Ten patients had myoclonus. The propositus, a 57-year-old man, suffered from repeated, intense, asymmetric flexion jerks of the lower extremities, alternating with fidgeting and friction movements of the legs; all occurred at night prior to sleep and severely interfering with it. The patient's movements ceased with the onset of stage 1 sleep, while in his brother, the motor activity persisted in stages 1 and 2 of sleep."} {"id": "PMID:1267635", "title": "Ophthalmoplegia and dissociated nystagmus in adetalipoproteinemia.", "content": "A characteristic pattern of acquired exotropia, progressive paresis of the medial rectus muscles, and dissociated nystagmus on lateral gaze was found in three patients with abetalipoproteinemia. Study with electronystagmography of the eye movements of one patient revealed abnormally slow voluntary saccades and slow or absent fast components of vestibular nystagmus, optokinetic nystagmus, and jerk-type, disassociated nystagmus. Defects in central nervous system centers generating saccadic eye movements are postulated.", "contents": "Ophthalmoplegia and dissociated nystagmus in adetalipoproteinemia. A characteristic pattern of acquired exotropia, progressive paresis of the medial rectus muscles, and dissociated nystagmus on lateral gaze was found in three patients with abetalipoproteinemia. Study with electronystagmography of the eye movements of one patient revealed abnormally slow voluntary saccades and slow or absent fast components of vestibular nystagmus, optokinetic nystagmus, and jerk-type, disassociated nystagmus. Defects in central nervous system centers generating saccadic eye movements are postulated."} {"id": "PMID:1267636", "title": "Migratory white-without-pressure retinal lesions.", "content": "Nine patients had white-without-pressure retinal lesions. These lesions were seen in areas of vitreoretinal adhesions. The configuration and location of these lesions changed over variable periods of time. The cause of this pecular migration is unknown, but may be related to separation and re-creation of vitreoretinal adhesions. The migratory nature of white-without-pressure areas has not, to our knowledge, previously been reported in the literature.", "contents": "Migratory white-without-pressure retinal lesions. Nine patients had white-without-pressure retinal lesions. These lesions were seen in areas of vitreoretinal adhesions. The configuration and location of these lesions changed over variable periods of time. The cause of this pecular migration is unknown, but may be related to separation and re-creation of vitreoretinal adhesions. The migratory nature of white-without-pressure areas has not, to our knowledge, previously been reported in the literature."} {"id": "PMID:1267637", "title": "Treatment of Behcet disease with chlorambucil. A follow-up report.", "content": "In Behcet disease the eyes are involved in most cases, and progression to blindness is almost the rule. When the central nervous system is involved, the prognosis for life is grave. In a preliminary report, 11 patients had the disease arrested as a result of treatment with chlorambucil. Some of these patients had long-term follow-up and are included in this report. Nine others received the same treatment, resulting in arrest of the disease in eight and pronounced improvement in one. Long-term follow-up, in some patients for more than five years after arrest of the disease, has not disclosed any recurrence. These results may appear more important if it is noted that blindness in Behcet disease occurs an average of 3.36 years after onset of eye symptoms.", "contents": "Treatment of Behcet disease with chlorambucil. A follow-up report. In Behcet disease the eyes are involved in most cases, and progression to blindness is almost the rule. When the central nervous system is involved, the prognosis for life is grave. In a preliminary report, 11 patients had the disease arrested as a result of treatment with chlorambucil. Some of these patients had long-term follow-up and are included in this report. Nine others received the same treatment, resulting in arrest of the disease in eight and pronounced improvement in one. Long-term follow-up, in some patients for more than five years after arrest of the disease, has not disclosed any recurrence. These results may appear more important if it is noted that blindness in Behcet disease occurs an average of 3.36 years after onset of eye symptoms."} {"id": "PMID:1267638", "title": "Herpes simplex keratitis in a developing country. Natural history and treatment of epithelial ulcers in Tunisia.", "content": "Herpes simplex keratitis was found to be a common ophthalmic problem in Tunisia. Dendritic and geographic ulcers were complicated by deep stromal keratitis in 31% of patients, two thirds of whom were known to have been treated previously with corticosteroids. Herpes simplex virus was isolated from 41% of patients from whom corneal material was cultured. To develop an effective program for management of epithelial herpes in developing countries, treatment with idoxuridine was compared with debridement and patching. Average healing time for 31 ulcers treated with idoxuridine was 13 days, with three treatment failures; average healing time for 20 ulcers treated with debridement and patching was five days, with one failure. Debridement and patching of herpetic ulcers was an efficient way to treat herpes simplex keratitis within the context of overall medical care in Tunisia.", "contents": "Herpes simplex keratitis in a developing country. Natural history and treatment of epithelial ulcers in Tunisia. Herpes simplex keratitis was found to be a common ophthalmic problem in Tunisia. Dendritic and geographic ulcers were complicated by deep stromal keratitis in 31% of patients, two thirds of whom were known to have been treated previously with corticosteroids. Herpes simplex virus was isolated from 41% of patients from whom corneal material was cultured. To develop an effective program for management of epithelial herpes in developing countries, treatment with idoxuridine was compared with debridement and patching. Average healing time for 31 ulcers treated with idoxuridine was 13 days, with three treatment failures; average healing time for 20 ulcers treated with debridement and patching was five days, with one failure. Debridement and patching of herpetic ulcers was an efficient way to treat herpes simplex keratitis within the context of overall medical care in Tunisia."} {"id": "PMID:1267639", "title": "Developing eye in an ovarian teratoma.", "content": "A malignant teratoma of the ovary was resected in a 14-year-old girl. Within the tumor, a partially developed eye was found.", "contents": "Developing eye in an ovarian teratoma. A malignant teratoma of the ovary was resected in a 14-year-old girl. Within the tumor, a partially developed eye was found."} {"id": "PMID:1267640", "title": "Senile mecular degeneration. A clinicopathologic correlation of two cases with neovascularization beneath the retinal pigment epithelium.", "content": "The histopathologic findings in two cases of senile macular degeneration were correlated with the premortem clinical studies, from the onset in both cases and through the disciform stage in one case. In case 2, the postmortem eyes were obtained only one month after ophthalmoscopic, fluorescein angiographic, and fundus photographic studies were performed, all on the same day. Our report not only adds to the few clinicopathologic correlations of the lesions in senile macular degeneration reported in the literature, but also presents the first reconstruction to scale of subretinal pigment epithelial (sub-RPE) neovascularization. Our results confirm the diagnosis of sub-RPE neovascularization and serous detachment of the retinal pigment epithelium. Drusen were correlated as to number and general location but not individually. Serous detachment of the neurosensory retina was found histopathologically but not clinically.", "contents": "Senile mecular degeneration. A clinicopathologic correlation of two cases with neovascularization beneath the retinal pigment epithelium. The histopathologic findings in two cases of senile macular degeneration were correlated with the premortem clinical studies, from the onset in both cases and through the disciform stage in one case. In case 2, the postmortem eyes were obtained only one month after ophthalmoscopic, fluorescein angiographic, and fundus photographic studies were performed, all on the same day. Our report not only adds to the few clinicopathologic correlations of the lesions in senile macular degeneration reported in the literature, but also presents the first reconstruction to scale of subretinal pigment epithelial (sub-RPE) neovascularization. Our results confirm the diagnosis of sub-RPE neovascularization and serous detachment of the retinal pigment epithelium. Drusen were correlated as to number and general location but not individually. Serous detachment of the neurosensory retina was found histopathologically but not clinically."} {"id": "PMID:1267641", "title": "Ocular findings six years after intravitreal silicone injection.", "content": "A case of giant retinal tear treated by injection with dimethicone 350 (medical fluid silicone) was observed for six years before enucleation. About four months after the injection, signs of anterior segment ischemia were evident. A year after the injection, an injury resulted in displacement of dimethicone 350 into the anterior chamber. Enucleation was done because of pain.", "contents": "Ocular findings six years after intravitreal silicone injection. A case of giant retinal tear treated by injection with dimethicone 350 (medical fluid silicone) was observed for six years before enucleation. About four months after the injection, signs of anterior segment ischemia were evident. A year after the injection, an injury resulted in displacement of dimethicone 350 into the anterior chamber. Enucleation was done because of pain."} {"id": "PMID:1267642", "title": "Cellular blue nevus of the sclera.", "content": "An isolated cellular blue nevus of the sclera was discovered and removed during a retinal detachment operation. Such benign tumors may be misdiagnosed clinically as an extension of a melanoma of the choroid or histologically as melanoma.", "contents": "Cellular blue nevus of the sclera. An isolated cellular blue nevus of the sclera was discovered and removed during a retinal detachment operation. Such benign tumors may be misdiagnosed clinically as an extension of a melanoma of the choroid or histologically as melanoma."} {"id": "PMID:1267643", "title": "Corneoscleral cautery. Pathology and technique.", "content": "The filtration procedures of trephine, iridencleisis, and corneoscleral cautery are compared to show the superiority of the latter. Pathologic vertification of the three operations suggests the reason for success. Several changes in the original technique as described by Schele are suggested.", "contents": "Corneoscleral cautery. Pathology and technique. The filtration procedures of trephine, iridencleisis, and corneoscleral cautery are compared to show the superiority of the latter. Pathologic vertification of the three operations suggests the reason for success. Several changes in the original technique as described by Schele are suggested."} {"id": "PMID:1267644", "title": "Intermittent vs continuous steroid administration. Efficacy in experimental conjunctivitis.", "content": "The development of techniques for the continuous administration of drugs to the eye raises the question of whether a conjunctivitis can be controlled by continuous low rates of steroid release, or whether large, intermittent doses of steroid, as provided by eyedrops, are necessary. Efficacy of the two modes of drug administration was evaluated in a conjunctivitis model produced in immunized rabbits by daily topical ocular challenge with antigen. The acetates of hydrocortisone and prednisolone were released from a drug delivery system inserted in the cul-de-sac of the eye or were provided in eyedrops. The model was sufficiently sensitive to differentiate between the effectiveness of hydrocortisone and prednisolone. The continuous delivery of either steroid from the drug delivery system was as efficacious, or more so, than the corresponding steroid dose given as eyedrops.", "contents": "Intermittent vs continuous steroid administration. Efficacy in experimental conjunctivitis. The development of techniques for the continuous administration of drugs to the eye raises the question of whether a conjunctivitis can be controlled by continuous low rates of steroid release, or whether large, intermittent doses of steroid, as provided by eyedrops, are necessary. Efficacy of the two modes of drug administration was evaluated in a conjunctivitis model produced in immunized rabbits by daily topical ocular challenge with antigen. The acetates of hydrocortisone and prednisolone were released from a drug delivery system inserted in the cul-de-sac of the eye or were provided in eyedrops. The model was sufficiently sensitive to differentiate between the effectiveness of hydrocortisone and prednisolone. The continuous delivery of either steroid from the drug delivery system was as efficacious, or more so, than the corresponding steroid dose given as eyedrops."} {"id": "PMID:1267645", "title": "A Ganzfeld stimulator for electroretinography.", "content": "The design of a ganzfeld stimulator for electroretinography affects both clinical results and ease of operation. Several advantageous design differences from a recently described ganzfeld stimulator are (1) close proximity of the flash electrode to the surface of the sphere to increase the intensity and uniformity of the stimulus; (2) provision for interposing color filters in the background light; (3) use of a diffusing filter in the background light; and (4) placement of the stimulus flash anteriorly to avoid uneven illumination of the retina. Details of construction are proveded for two models and the specific advantages of each design are noted.", "contents": "A Ganzfeld stimulator for electroretinography. The design of a ganzfeld stimulator for electroretinography affects both clinical results and ease of operation. Several advantageous design differences from a recently described ganzfeld stimulator are (1) close proximity of the flash electrode to the surface of the sphere to increase the intensity and uniformity of the stimulus; (2) provision for interposing color filters in the background light; (3) use of a diffusing filter in the background light; and (4) placement of the stimulus flash anteriorly to avoid uneven illumination of the retina. Details of construction are proveded for two models and the specific advantages of each design are noted."} {"id": "PMID:1267646", "title": "Hypotension and bradycardia following intraocular acetylcholine injection. Report of a case.", "content": "A possible systemic reaction to acetylcholine chloride injected into the anterior chamber of the eye occurred in a 65-year-old patient who had a cataract extraction while under general anesthesia. Following cataract extraction, 20 mg of acetylcholine chloride was injected into the anterior chamber of the eye. Immediately following injection, hypotension and bradycardia (48 beats per minute) occurred.", "contents": "Hypotension and bradycardia following intraocular acetylcholine injection. Report of a case. A possible systemic reaction to acetylcholine chloride injected into the anterior chamber of the eye occurred in a 65-year-old patient who had a cataract extraction while under general anesthesia. Following cataract extraction, 20 mg of acetylcholine chloride was injected into the anterior chamber of the eye. Immediately following injection, hypotension and bradycardia (48 beats per minute) occurred."} {"id": "PMID:1267651", "title": "Retinal vascular changes of incontinentia pigmenti.", "content": "Of 19 patients with incontinentia pigmenti, seven had a bizarre retinal anomaly that consisted of a zone of abnormal arteriovenous connections and preretinal fibrotic tissue at the temporal equator, with no perfusion peripheral to it. In one patient, the vascular changes progressed and required photocoagulation. This retinal lesion may represent an early stage of the pseudoglioma that so commonly is reported with this skin disease. Incontinentia pigmenti should be considered in the differential diagnosis of retinal vascular disease in girls and women of any age.", "contents": "Retinal vascular changes of incontinentia pigmenti. Of 19 patients with incontinentia pigmenti, seven had a bizarre retinal anomaly that consisted of a zone of abnormal arteriovenous connections and preretinal fibrotic tissue at the temporal equator, with no perfusion peripheral to it. In one patient, the vascular changes progressed and required photocoagulation. This retinal lesion may represent an early stage of the pseudoglioma that so commonly is reported with this skin disease. Incontinentia pigmenti should be considered in the differential diagnosis of retinal vascular disease in girls and women of any age."} {"id": "PMID:1267652", "title": "Visual field changes in branch retinal 'vein' occlusion.", "content": "The visual field defects in 20 consecutive patients who had branch retinal \"vein\" occlusions included arcuate nerve fiber bundle scotomas, central scotomas, paracentral scotomas, and segmental peripheral constriction. The role of retinal arteriolar insufficiency in the production of these field defects is discussed. The available evidence suggests that the term \"branch retinal vascular occlusion\" is a preferable term to describe such clinical findings.", "contents": "Visual field changes in branch retinal 'vein' occlusion. The visual field defects in 20 consecutive patients who had branch retinal \"vein\" occlusions included arcuate nerve fiber bundle scotomas, central scotomas, paracentral scotomas, and segmental peripheral constriction. The role of retinal arteriolar insufficiency in the production of these field defects is discussed. The available evidence suggests that the term \"branch retinal vascular occlusion\" is a preferable term to describe such clinical findings."} {"id": "PMID:1267653", "title": "Disciform degeneration of the macula. II. Pathogenesis.", "content": "Of 84 patients with unilateral disciform macular degeneration, 36 were followed up for one to four years (average, 22 months). The fellow eye in 13 cases developed disciform lesions during that follow-up period. A significantly greater number of drusen were found in the fellow eyes of patients with unilateral disciform macular degeneration than in the eyes of a comparable control group of patients (P less than .001). Furthermore, the eyes with unilateral disciform macular degeneration that developed disciform lesions in the other eye were characterized as a group by a significantly larger number of drusen than those that did not. We postulate that drusen are precursors of disciform macular degeneration in fellow eyes and are probably manifestations of the same exudative process.", "contents": "Disciform degeneration of the macula. II. Pathogenesis. Of 84 patients with unilateral disciform macular degeneration, 36 were followed up for one to four years (average, 22 months). The fellow eye in 13 cases developed disciform lesions during that follow-up period. A significantly greater number of drusen were found in the fellow eyes of patients with unilateral disciform macular degeneration than in the eyes of a comparable control group of patients (P less than .001). Furthermore, the eyes with unilateral disciform macular degeneration that developed disciform lesions in the other eye were characterized as a group by a significantly larger number of drusen than those that did not. We postulate that drusen are precursors of disciform macular degeneration in fellow eyes and are probably manifestations of the same exudative process."} {"id": "PMID:1267654", "title": "Unilateral medial rectus recession for small-angle esotropia.", "content": "Ten patients with small-angle esotropia of 18 prism diopters or less were treated with a unilateral medial rectus recession of 5 mm. Nine of the ten cases considerably improved; one showed only minimal improvement. There were no overcorrections, but two cases did show lateral incomitance with a greater correction on gaze in the field of action of the recessed medial rectus muscle. Two patients became monofixators after the surgery. These had been patients with accommodative esotropia who had decompensated and had surgery for the nonaccommodative portion of the total esotropia. When indicated, the recession of one medial rectus muscle is a safe and predictable procedure for small-angle esotropia. An average correction of 11.6 prism diopters was obtained at distance and one of 11.3 prism diopters at near.", "contents": "Unilateral medial rectus recession for small-angle esotropia. Ten patients with small-angle esotropia of 18 prism diopters or less were treated with a unilateral medial rectus recession of 5 mm. Nine of the ten cases considerably improved; one showed only minimal improvement. There were no overcorrections, but two cases did show lateral incomitance with a greater correction on gaze in the field of action of the recessed medial rectus muscle. Two patients became monofixators after the surgery. These had been patients with accommodative esotropia who had decompensated and had surgery for the nonaccommodative portion of the total esotropia. When indicated, the recession of one medial rectus muscle is a safe and predictable procedure for small-angle esotropia. An average correction of 11.6 prism diopters was obtained at distance and one of 11.3 prism diopters at near."} {"id": "PMID:1267655", "title": "Acute orbital cellulitis.", "content": "A review of 104 patients with acute orbital cellulitis during the past decade showed that the frequency of hospital admissions for this disease has increased recently. Roentgenograms showed paranasal sinus in 77 of 91 patients. Haemophilus influenzae and Diplococcus pneumoniae were recovered from the blood of 20 and 6 patients, respectively. Four children had concomitant H influenzae meningitis. Bacteremia was demonstrated in 29% and more common in those with extensive orbital involvement, those not receiving antibiotics at the time of culture, and those less than 2 years old. Some of the 26 patients with less extensive involvement were bacteremic (17%), had leukocytosis, or roentgenographic evidence of sinusitis. Most children received large doses of ampicillin sodium and methicillin sodium intravenously until signs and symptoms had almost abated. With this regimen, there were no orbital, ocular, or other complications.", "contents": "Acute orbital cellulitis. A review of 104 patients with acute orbital cellulitis during the past decade showed that the frequency of hospital admissions for this disease has increased recently. Roentgenograms showed paranasal sinus in 77 of 91 patients. Haemophilus influenzae and Diplococcus pneumoniae were recovered from the blood of 20 and 6 patients, respectively. Four children had concomitant H influenzae meningitis. Bacteremia was demonstrated in 29% and more common in those with extensive orbital involvement, those not receiving antibiotics at the time of culture, and those less than 2 years old. Some of the 26 patients with less extensive involvement were bacteremic (17%), had leukocytosis, or roentgenographic evidence of sinusitis. Most children received large doses of ampicillin sodium and methicillin sodium intravenously until signs and symptoms had almost abated. With this regimen, there were no orbital, ocular, or other complications."} {"id": "PMID:1267656", "title": "Lamellar macular hole: a complication of cystoid macular edema after cataract extraction.", "content": "A woman developed an inner lamellar macular hole and cellophane maculopathy as a complication of chronic cystoid macular edema following cataract extraction. Fluorescein angiography revealed a cystoid pattern of fluorescence in the paracentral area but no evidence of staining in the region of the hole. Following death, histopathologic examination of both eyes confirmed the clinical observations. Biomicroscopic examination and fluorescein angiography are of value in differentiating an inner lamellar macular hole from a full-thickness macular hole and from a pseudomacular hole caused by spontaneous contraction of an epiretinal membrane.", "contents": "Lamellar macular hole: a complication of cystoid macular edema after cataract extraction. A woman developed an inner lamellar macular hole and cellophane maculopathy as a complication of chronic cystoid macular edema following cataract extraction. Fluorescein angiography revealed a cystoid pattern of fluorescence in the paracentral area but no evidence of staining in the region of the hole. Following death, histopathologic examination of both eyes confirmed the clinical observations. Biomicroscopic examination and fluorescein angiography are of value in differentiating an inner lamellar macular hole from a full-thickness macular hole and from a pseudomacular hole caused by spontaneous contraction of an epiretinal membrane."} {"id": "PMID:1267658", "title": "Effects of microwave radiation on the lens epithelium in the rabbit eye.", "content": "These experiments were conducted to determine the effect of cataractogenic doses of microwave radiation at 2.45 gigahertz (GHz) on the lens epithelium of the rabbit. One hour before animals were killed, tritiated thymidine was injected into the anterior chamber of both eyes at postirradiation intervals varying from six hours to one month. Epithelial peels were made and autoradiographic techniques used to identify cells manufacturing DNA. Comparison of counts from both experimental and control epithelia revealed two patterns, depending on the presence or absence of vesicle strings. Those lenses without vesicle strings showed an initial pronounced suppression of mitotic activity followed by gradual return to normal levels. Those lenses with strings showed a precipitous rise in DNA synthesis on the fourth to fifth day after irradiation. This increased activity may be the result of lens hydration.", "contents": "Effects of microwave radiation on the lens epithelium in the rabbit eye. These experiments were conducted to determine the effect of cataractogenic doses of microwave radiation at 2.45 gigahertz (GHz) on the lens epithelium of the rabbit. One hour before animals were killed, tritiated thymidine was injected into the anterior chamber of both eyes at postirradiation intervals varying from six hours to one month. Epithelial peels were made and autoradiographic techniques used to identify cells manufacturing DNA. Comparison of counts from both experimental and control epithelia revealed two patterns, depending on the presence or absence of vesicle strings. Those lenses without vesicle strings showed an initial pronounced suppression of mitotic activity followed by gradual return to normal levels. Those lenses with strings showed a precipitous rise in DNA synthesis on the fourth to fifth day after irradiation. This increased activity may be the result of lens hydration."} {"id": "PMID:1267659", "title": "Battered child syndrome simulating congenital glaucoma.", "content": "A 9-week-old child with \"congenital glaucoma\" was later found to have, in addition to enlarged corneas and elevated intraocular pressure, subluxated and cataractous lenses, hyphema, iridodialysis, angle recession, and vitreous hemorrhage, along with signs of gross parental neglect and physical abuse. To our knowledge, this is the first report in which a battered child with bilateral \"congenital glaucoma\" (probably caused by trauma) is described.", "contents": "Battered child syndrome simulating congenital glaucoma. A 9-week-old child with \"congenital glaucoma\" was later found to have, in addition to enlarged corneas and elevated intraocular pressure, subluxated and cataractous lenses, hyphema, iridodialysis, angle recession, and vitreous hemorrhage, along with signs of gross parental neglect and physical abuse. To our knowledge, this is the first report in which a battered child with bilateral \"congenital glaucoma\" (probably caused by trauma) is described."} {"id": "PMID:1267660", "title": "Anterior segment ischemia following the Jensen procedure.", "content": "Anterior segment ischemia occurred in a 66-year-old patient following recession of one medial rectus muscle combined with lateral rectus muscle union to the vertical rectus muscles (Jensen procedure). The mechanism of this complication is explained as inadvertent strangulation of the anterior ciliary arteries during tying of the split lateral rectus to the temporal aspects of the vertical rectus muscles. Special efforts to preserve the integrity of anterior ciliary arteries in those portions of the vertical rectus muscles not involved in the muscle union should be made to avoid this complication.", "contents": "Anterior segment ischemia following the Jensen procedure. Anterior segment ischemia occurred in a 66-year-old patient following recession of one medial rectus muscle combined with lateral rectus muscle union to the vertical rectus muscles (Jensen procedure). The mechanism of this complication is explained as inadvertent strangulation of the anterior ciliary arteries during tying of the split lateral rectus to the temporal aspects of the vertical rectus muscles. Special efforts to preserve the integrity of anterior ciliary arteries in those portions of the vertical rectus muscles not involved in the muscle union should be made to avoid this complication."} {"id": "PMID:1267664", "title": "[Experimental \"hormonal tenolysis\" by cortisone therapy (author's transl)].", "content": "To prevent tendons from postoperative proliferation and adhesion to surrounding structures is still a main problem in handsurgery. In addition to numerous modifications of atraumatic handsurgical techniques which have been developed some sporadic attempts are made by animal experiments and clinical trials in order to avoid postoperative adhesive tenosynovitis by hormone therapy. Because of the high doses of cortisone which are required this method of treatment is generally not accepted. Using a new method of postoperative fixation of flexor tendon sutures in rabbits the possibility of a \"hormonal tenolysis\" by extremely high doses of cortisone could be confirmed. In a following study it is planned to perform breaking experiments on tendons after hormone therapy in order to determine the upper limit of the therapeutical range of cortisone medication.", "contents": "[Experimental \"hormonal tenolysis\" by cortisone therapy (author's transl)]. To prevent tendons from postoperative proliferation and adhesion to surrounding structures is still a main problem in handsurgery. In addition to numerous modifications of atraumatic handsurgical techniques which have been developed some sporadic attempts are made by animal experiments and clinical trials in order to avoid postoperative adhesive tenosynovitis by hormone therapy. Because of the high doses of cortisone which are required this method of treatment is generally not accepted. Using a new method of postoperative fixation of flexor tendon sutures in rabbits the possibility of a \"hormonal tenolysis\" by extremely high doses of cortisone could be confirmed. In a following study it is planned to perform breaking experiments on tendons after hormone therapy in order to determine the upper limit of the therapeutical range of cortisone medication."} {"id": "PMID:1267665", "title": "[Closed injuries to capsular and ligamentous structure of MP I joint--diagnosis and treatment (author's transl)].", "content": "7 new and 9 old injuries of the MP I joint primarily involving the ulnar capsule and ligaments have been reevaluated for treatnent and results. In old cases, the operative result could be classified as excellent and good in 7, while 2 were considered as failures. These results have been used to discuss the mechanism and diagnosis of ruptures of the MP I joint ligaments. Primary surgical treatment of fresh ligamentous injuries is far superior than plastic reconstruction of old injuries.", "contents": "[Closed injuries to capsular and ligamentous structure of MP I joint--diagnosis and treatment (author's transl)]. 7 new and 9 old injuries of the MP I joint primarily involving the ulnar capsule and ligaments have been reevaluated for treatnent and results. In old cases, the operative result could be classified as excellent and good in 7, while 2 were considered as failures. These results have been used to discuss the mechanism and diagnosis of ruptures of the MP I joint ligaments. Primary surgical treatment of fresh ligamentous injuries is far superior than plastic reconstruction of old injuries."} {"id": "PMID:1267666", "title": "[Some aspects concerning the problem of lesions of the ulnar collateral ligament of the thumb (author's transl)].", "content": "The authors report on their experience on 20 old lesions of the ulnar collateral ligament of the MP joint of the thumb. They used a modified technique according to Strandell.--Follow up investigations were made in an average range of 17.5 months after the operation. All the colateral ligaments were stable. The procedure is not to be used for heavy manual working persons. If there is an osteoarthritis in the MP joint, arthrodesis is the alternative method.", "contents": "[Some aspects concerning the problem of lesions of the ulnar collateral ligament of the thumb (author's transl)]. The authors report on their experience on 20 old lesions of the ulnar collateral ligament of the MP joint of the thumb. They used a modified technique according to Strandell.--Follow up investigations were made in an average range of 17.5 months after the operation. All the colateral ligaments were stable. The procedure is not to be used for heavy manual working persons. If there is an osteoarthritis in the MP joint, arthrodesis is the alternative method."} {"id": "PMID:1267667", "title": "The treatment of chronic knee joint synovitis with radioactive isotops (author's transl).", "content": "On the basis of 77 cases report is given on the treatment of chronic synovitis of the knee in rheumatoid arthritis with radioactive isotopes. Gold 198 and Yttrium90 have been applicated. During an observation period up to 6 years a follow-up on 46 knee joints has been carried out. Very good and good results could be achieved in 50% of these cases.", "contents": "The treatment of chronic knee joint synovitis with radioactive isotops (author's transl). On the basis of 77 cases report is given on the treatment of chronic synovitis of the knee in rheumatoid arthritis with radioactive isotopes. Gold 198 and Yttrium90 have been applicated. During an observation period up to 6 years a follow-up on 46 knee joints has been carried out. Very good and good results could be achieved in 50% of these cases."} {"id": "PMID:1267668", "title": "[Fundamental biomechanic problems on osteosynthesis (author's transl)].", "content": "By means of compression plate osteosynthesis, of the lateral tension band and of the treatment with external chucks the main demand for stability of osteosynthesises is derivated: by adjustified, in the resultant axial tension of the metal implantats is to produce only pressure in the entire fracture zone without detrimental osteosynthesis induced excentric powers. The joint biomechanic aspects of the three methods are worked out.", "contents": "[Fundamental biomechanic problems on osteosynthesis (author's transl)]. By means of compression plate osteosynthesis, of the lateral tension band and of the treatment with external chucks the main demand for stability of osteosynthesises is derivated: by adjustified, in the resultant axial tension of the metal implantats is to produce only pressure in the entire fracture zone without detrimental osteosynthesis induced excentric powers. The joint biomechanic aspects of the three methods are worked out."} {"id": "PMID:1267669", "title": "[Stresses on osteosyntheses of femur and tibia in early mobilisation (author's transl)].", "content": "The knowledge of post surgery strain is of fundamental significance for dimension and location of application of osteosynthesis. In the following biomechanical research height and direction of moments of flexure will be determined that occur during sleep and/or anaesthesia without additional and at partially loaded early mobilisation with the muscle activity at course of doppel step at upright- and swing-leg position. Moments of flexure are calculated at frontal and sagittal level considering efficiency of weights of parts of the leg and their centres of gravity as well as bending efficiency of the active muscle groups. Thus, moments of flexure resulting important facts are found for dimenstion of osteosynthesis equipments.", "contents": "[Stresses on osteosyntheses of femur and tibia in early mobilisation (author's transl)]. The knowledge of post surgery strain is of fundamental significance for dimension and location of application of osteosynthesis. In the following biomechanical research height and direction of moments of flexure will be determined that occur during sleep and/or anaesthesia without additional and at partially loaded early mobilisation with the muscle activity at course of doppel step at upright- and swing-leg position. Moments of flexure are calculated at frontal and sagittal level considering efficiency of weights of parts of the leg and their centres of gravity as well as bending efficiency of the active muscle groups. Thus, moments of flexure resulting important facts are found for dimenstion of osteosynthesis equipments."} {"id": "PMID:1267670", "title": "[The vessel behavior of the bone following plate osteosynthesis and subsequent osteomyelitis. An experimental study at the dog tibia (author's transl)].", "content": "In this paper the revascularisation pattern of the dog tibia diaphyse following osteotomy and plate osteosynthesis with subsequent osteomyelitis is described at various stages. As compared to undisturbed plate osteosynthesis the differences and conformities in revascularisation are shown. It is attempted to interpret the vessel behaviour under clinical aspects.", "contents": "[The vessel behavior of the bone following plate osteosynthesis and subsequent osteomyelitis. An experimental study at the dog tibia (author's transl)]. In this paper the revascularisation pattern of the dog tibia diaphyse following osteotomy and plate osteosynthesis with subsequent osteomyelitis is described at various stages. As compared to undisturbed plate osteosynthesis the differences and conformities in revascularisation are shown. It is attempted to interpret the vessel behaviour under clinical aspects."} {"id": "PMID:1267671", "title": "[New aspects for enlargement of surgical x-rays (author's transl)].", "content": "Method of direct geometrical X-ray magnification technique are discussed in the light of new technical possibilities,--fine-focus, high speed screen--and- the value in surgical X-ray diagnosis for the fine bone structure changes is demonstrated using practical examples. Also mentioned are other methods for a quirering a better form of diagnosis--such as for example the harmonising method.", "contents": "[New aspects for enlargement of surgical x-rays (author's transl)]. Method of direct geometrical X-ray magnification technique are discussed in the light of new technical possibilities,--fine-focus, high speed screen--and- the value in surgical X-ray diagnosis for the fine bone structure changes is demonstrated using practical examples. Also mentioned are other methods for a quirering a better form of diagnosis--such as for example the harmonising method."} {"id": "PMID:1267672", "title": "[Late results in hemialloarthroplasty of the hip (author's transl)].", "content": "This paper presents a study of long-term results of femoral head replacement. 104 patients with Moore prosthesis could be followed up for an average of 9 1/2 years. In cases of fractures and complications of trauma the results were excellent and good in 65%. Practically 100% poor results could be shown in patients with osteoarthritis", "contents": "[Late results in hemialloarthroplasty of the hip (author's transl)]. This paper presents a study of long-term results of femoral head replacement. 104 patients with Moore prosthesis could be followed up for an average of 9 1/2 years. In cases of fractures and complications of trauma the results were excellent and good in 65%. Practically 100% poor results could be shown in patients with osteoarthritis"} {"id": "PMID:1267673", "title": "Stresses and functional adaptation of alloarthroplasty of the proximal femur in dogs using a selfcuring rippled prosthesis. A comparative biomechanical and morphological study (author's transl).", "content": "A self-adhesive prosthesis for youth patients is developed by Mittelmeier that is implanted without bone cement. After an implantation term of 1 year in animal experiment (dog), an adapted femur is compared with the contra-lateral normal femur. Strain gauges are used to determine bone strain under load. Further is determined external and internal construction change after endoprosthesis. The construction changes found are in connection with the changed bone strength. A cancellous change of bone at entire area of stem of prosthesis is called a \"metaphysation\" of bone shaft.", "contents": "Stresses and functional adaptation of alloarthroplasty of the proximal femur in dogs using a selfcuring rippled prosthesis. A comparative biomechanical and morphological study (author's transl). A self-adhesive prosthesis for youth patients is developed by Mittelmeier that is implanted without bone cement. After an implantation term of 1 year in animal experiment (dog), an adapted femur is compared with the contra-lateral normal femur. Strain gauges are used to determine bone strain under load. Further is determined external and internal construction change after endoprosthesis. The construction changes found are in connection with the changed bone strength. A cancellous change of bone at entire area of stem of prosthesis is called a \"metaphysation\" of bone shaft."} {"id": "PMID:1267674", "title": "[Biomechanical and clinical studies of the transnaviculo-lunar resection arthroplasty (Steinh\u00e4user operation) (author's transl)].", "content": "In advanced injuries of the proximal carpal row there is a therapeutic alternative to other methods of treatment--the Transnaviculo-Lunar Resection Arthroplasty of J. Steinh\u00e4user. This operation gives the possibility to form a new joint by removing the os lumatum and the proximal two thirds of the os naviculare. The result is a painless new wrist which has a good range of motion. Since 1968 six Steinh\u00e4user operations have been performed by attending orthopaedic surgeons of the \"Orthop\u00e4dische Klinik M\u00fcnchen Harlaching\" follow-up study reports this clinical and radiographic results as well as the biomechanical fundamentales of the new wrist. The objective clinical and radiographic criterions, the subjective satisfaction of our patients and the biomechanical stability of the new wrist have shown, that there is a good prognosis of the Steinh\u00e4user operation.", "contents": "[Biomechanical and clinical studies of the transnaviculo-lunar resection arthroplasty (Steinh\u00e4user operation) (author's transl)]. In advanced injuries of the proximal carpal row there is a therapeutic alternative to other methods of treatment--the Transnaviculo-Lunar Resection Arthroplasty of J. Steinh\u00e4user. This operation gives the possibility to form a new joint by removing the os lumatum and the proximal two thirds of the os naviculare. The result is a painless new wrist which has a good range of motion. Since 1968 six Steinh\u00e4user operations have been performed by attending orthopaedic surgeons of the \"Orthop\u00e4dische Klinik M\u00fcnchen Harlaching\" follow-up study reports this clinical and radiographic results as well as the biomechanical fundamentales of the new wrist. The objective clinical and radiographic criterions, the subjective satisfaction of our patients and the biomechanical stability of the new wrist have shown, that there is a good prognosis of the Steinh\u00e4user operation."} {"id": "PMID:1267675", "title": "[Further experiences with total hip arthroplasty. Clinical and roentgenographic results after 3--6 years following implantation (author's transl)].", "content": "Report on 236 re-examined total hip arthroplasties performed between 3 and 6 years before (69 Huggler-Weber I and 167 McKee-Farrar joints). 76% of the patients were satisfied with their results on the base of acceptable pain control, increased joint mobility and improved functional capacity. Negative estimations usually could be verified by clinical and roentgenographic findings, the main reason for failures being aseptic loosening of one or both of the implant components in a present rate of 17.8%. Additional failures were due to infectious loosening (2.7%) and pararticular ossification (1.3%). Aseptic loosening of Weber-Huggler implants (33%) occured three times as often as with McKee-Farrar joints and usually was confined to the acetabulum. The influence of different factors such as patient's age and previous surgery, preoperative roentgenographic findings, etiology of coxarthrosis and operative technique has been evaluated. It is concluded that the present way of implant cementation with acrylics offers no sufficient long term anchorage and total hip arthroplasty therefore presently should be confined to the elderly. However, the results may be improved by strict indication and proper surgical technique.", "contents": "[Further experiences with total hip arthroplasty. Clinical and roentgenographic results after 3--6 years following implantation (author's transl)]. Report on 236 re-examined total hip arthroplasties performed between 3 and 6 years before (69 Huggler-Weber I and 167 McKee-Farrar joints). 76% of the patients were satisfied with their results on the base of acceptable pain control, increased joint mobility and improved functional capacity. Negative estimations usually could be verified by clinical and roentgenographic findings, the main reason for failures being aseptic loosening of one or both of the implant components in a present rate of 17.8%. Additional failures were due to infectious loosening (2.7%) and pararticular ossification (1.3%). Aseptic loosening of Weber-Huggler implants (33%) occured three times as often as with McKee-Farrar joints and usually was confined to the acetabulum. The influence of different factors such as patient's age and previous surgery, preoperative roentgenographic findings, etiology of coxarthrosis and operative technique has been evaluated. It is concluded that the present way of implant cementation with acrylics offers no sufficient long term anchorage and total hip arthroplasty therefore presently should be confined to the elderly. However, the results may be improved by strict indication and proper surgical technique."} {"id": "PMID:1267676", "title": "[Pitfalls of statistics as shown in a study on dysplastic hips (author's transl)].", "content": "In 97 cases of randomly selected children of an age from 5 to 16 weeks the angles of Hilgenreiner are determined. In relation to these findings also the influence of various factors such as hereditary anamnesis and untimely birth are observed. The so found data are compared with those published from T\u00f6nnis and Brunken. It seems that their data are higher than those in an average population. The necessity of an exact random test is pointed out.", "contents": "[Pitfalls of statistics as shown in a study on dysplastic hips (author's transl)]. In 97 cases of randomly selected children of an age from 5 to 16 weeks the angles of Hilgenreiner are determined. In relation to these findings also the influence of various factors such as hereditary anamnesis and untimely birth are observed. The so found data are compared with those published from T\u00f6nnis and Brunken. It seems that their data are higher than those in an average population. The necessity of an exact random test is pointed out."} {"id": "PMID:1267677", "title": "[Ultrastructural changes of human skeletal muscle after tendon and nerve injuries. I. Fine-structural changes of the hand muscles after tendor injuries (author's transl)].", "content": "During reconstructive procedures performed 4--16 weeks after the tendon lesion the specimens obtained from the injured muscle have been examined by the authors. It was found that after the tendon injury inactivity atrophy develops and a condition of equilibrum could be observed at this time. The most important changes in the fine structure were seen in the contractile elements: there were atrophied, homogenized, fragmentated and ragged independently from the functional unities. The number of the mitochondria was considerably decreased, the sarcoplasmatic reticulum was increased, and the difference between the originally red and white muscular fibres was indistinct. The glycogen content of the musculature was decreased, or it disappeared completely. No pathological changes have been observed in the sarcolemme, the cell nuclei and the motor nerve end-plates.", "contents": "[Ultrastructural changes of human skeletal muscle after tendon and nerve injuries. I. Fine-structural changes of the hand muscles after tendor injuries (author's transl)]. During reconstructive procedures performed 4--16 weeks after the tendon lesion the specimens obtained from the injured muscle have been examined by the authors. It was found that after the tendon injury inactivity atrophy develops and a condition of equilibrum could be observed at this time. The most important changes in the fine structure were seen in the contractile elements: there were atrophied, homogenized, fragmentated and ragged independently from the functional unities. The number of the mitochondria was considerably decreased, the sarcoplasmatic reticulum was increased, and the difference between the originally red and white muscular fibres was indistinct. The glycogen content of the musculature was decreased, or it disappeared completely. No pathological changes have been observed in the sarcolemme, the cell nuclei and the motor nerve end-plates."} {"id": "PMID:1267678", "title": "[Ultrastructural changes of human skeletal muscle after tendon and nerve injuries. II. Fine-structural alterations of the hand muscles after injuries of the motor nerve (author's transl)].", "content": "The authors examined the fine structural alterations of the muscles after traumatic neurotomy. The most important changes were forro found on the contractile elements, especially atrophy, and fragmentation. The number of mitochondria and sarcoplasmatic reticulum decreased both the glycogen content of sarcoplasma increased. The motor end plates were complete destroyed. On the motor motor-neurons typical Wallerian degeneration could be seen.", "contents": "[Ultrastructural changes of human skeletal muscle after tendon and nerve injuries. II. Fine-structural alterations of the hand muscles after injuries of the motor nerve (author's transl)]. The authors examined the fine structural alterations of the muscles after traumatic neurotomy. The most important changes were forro found on the contractile elements, especially atrophy, and fragmentation. The number of mitochondria and sarcoplasmatic reticulum decreased both the glycogen content of sarcoplasma increased. The motor end plates were complete destroyed. On the motor motor-neurons typical Wallerian degeneration could be seen."} {"id": "PMID:1267679", "title": "[Malignant degeneration of fistulas in chronic osteomyelitis (author's transl)].", "content": "The malignant degeneration of a skin ulcer has been reported as early as in 1884. In spite of this, however, the danger of malignant degeneration of sinus tracts associated with recurrences of chronic osteomyelitis is still underestimated. This development is neither restricted to case histories of years and decenniums nor to elderly patients and may also involve any part of the skeleton. Usually patients become aware of suddenly increasing tenderness and purulation, \"washed out\" structures of osteolytic areas are demonstrable radiographically. Diagnosis is established by mandatory histological examination of sinus tracts. Amputation or exarticulation of the extremity involved including efferent lymphatic vessels and nodi has no alternative. Local measures are insufficient. Apparently the first 3 years are decisive as to the prognosis. The prophylaxis consists of the therapy of the original disease: radical debridement of the osteomyelitic focus and filling of the defect with autogenous cancellous bone grafts.", "contents": "[Malignant degeneration of fistulas in chronic osteomyelitis (author's transl)]. The malignant degeneration of a skin ulcer has been reported as early as in 1884. In spite of this, however, the danger of malignant degeneration of sinus tracts associated with recurrences of chronic osteomyelitis is still underestimated. This development is neither restricted to case histories of years and decenniums nor to elderly patients and may also involve any part of the skeleton. Usually patients become aware of suddenly increasing tenderness and purulation, \"washed out\" structures of osteolytic areas are demonstrable radiographically. Diagnosis is established by mandatory histological examination of sinus tracts. Amputation or exarticulation of the extremity involved including efferent lymphatic vessels and nodi has no alternative. Local measures are insufficient. Apparently the first 3 years are decisive as to the prognosis. The prophylaxis consists of the therapy of the original disease: radical debridement of the osteomyelitic focus and filling of the defect with autogenous cancellous bone grafts."} {"id": "PMID:1267680", "title": "[The results of open reduction of distal tibial epiphyseal injuries (author's transl)].", "content": "This article contains a report of 16 open reductions of distal tibial epiphyseal injuries. The follow-up studies were carried out 1 1/2 to 6 years post-operatively. The results were excellent in all cases. A discussison of the surgical indications of these injuries is included.", "contents": "[The results of open reduction of distal tibial epiphyseal injuries (author's transl)]. This article contains a report of 16 open reductions of distal tibial epiphyseal injuries. The follow-up studies were carried out 1 1/2 to 6 years post-operatively. The results were excellent in all cases. A discussison of the surgical indications of these injuries is included."} {"id": "PMID:1267681", "title": "[Fresh combination injuries of the knee joint--diagnosis and treatment (author's transl)].", "content": "The diagnosis of fresh combination injuries of the knee joint is difficult. It is under all circumstances mandatory, occasionally by employing general anesthesia, to establish a diagnosis and the extend of the injury to decide on a conservative or surgical approach. Partial ruptures of the capsule and ligaments may be treated conservatively, complete ruptures are a surgical must. Between 1963 and 1974 we operated on 35 knees in 34 patients after afresh combination injury of the knee joint. 14 patients (15 knees) could be followed between 2 and 10 years postoperatively. All patients were satisfied with the result and were participating in sports. The objective results were excellent in 2, good in 12 and sufficient in 1. Knee joint stability could be reestablished in all knees. Follow-ups of a similar group of 14 patients after reconstructive treatment of an old \"unhappy triad\" showed considerably poorer results both subjectively and objectively. We conclude that fresh complete ruptures of the ligamentous and capsular structures of the knee joint have to be surgically repaired immediately to prevent permanent damage.", "contents": "[Fresh combination injuries of the knee joint--diagnosis and treatment (author's transl)]. The diagnosis of fresh combination injuries of the knee joint is difficult. It is under all circumstances mandatory, occasionally by employing general anesthesia, to establish a diagnosis and the extend of the injury to decide on a conservative or surgical approach. Partial ruptures of the capsule and ligaments may be treated conservatively, complete ruptures are a surgical must. Between 1963 and 1974 we operated on 35 knees in 34 patients after afresh combination injury of the knee joint. 14 patients (15 knees) could be followed between 2 and 10 years postoperatively. All patients were satisfied with the result and were participating in sports. The objective results were excellent in 2, good in 12 and sufficient in 1. Knee joint stability could be reestablished in all knees. Follow-ups of a similar group of 14 patients after reconstructive treatment of an old \"unhappy triad\" showed considerably poorer results both subjectively and objectively. We conclude that fresh complete ruptures of the ligamentous and capsular structures of the knee joint have to be surgically repaired immediately to prevent permanent damage."} {"id": "PMID:1267682", "title": "[Fractures of the olecranon; late results (authors's transl)].", "content": "140 fractures of the olecranon were treated (69 conservatively, 71 surgically), of whom 71 were followed up (28 conservative, 43 operated fractures). The fractures are classified in 4 groups (A. transverse fractures, B. oblique fractures, C. comminuted fractures and D. fractures associated with other injuries in the elbow joint). Each of these groups is devided into 3 types according to the displacement of the fragments. Good results by conservative treatment were always seen in fractures with separation of the fragments less than 2 mm. A relative indication for surgical treatment is displacement from 2 up to 10 mm. Only surgical treatment can prevent non-union in fractures with separation of the fragments more than 10 mm. A new sheme for classification of the results is proposed, and late results of the followed up cases are reported. Immobilization of the elbow in full extension is rejected in the conservative treatment. The internal fixation of prestress type by the Weber technique and the osteosynthesis with Spongiosa-screw are the preponderant methods actually used in surgical treatment.", "contents": "[Fractures of the olecranon; late results (authors's transl)]. 140 fractures of the olecranon were treated (69 conservatively, 71 surgically), of whom 71 were followed up (28 conservative, 43 operated fractures). The fractures are classified in 4 groups (A. transverse fractures, B. oblique fractures, C. comminuted fractures and D. fractures associated with other injuries in the elbow joint). Each of these groups is devided into 3 types according to the displacement of the fragments. Good results by conservative treatment were always seen in fractures with separation of the fragments less than 2 mm. A relative indication for surgical treatment is displacement from 2 up to 10 mm. Only surgical treatment can prevent non-union in fractures with separation of the fragments more than 10 mm. A new sheme for classification of the results is proposed, and late results of the followed up cases are reported. Immobilization of the elbow in full extension is rejected in the conservative treatment. The internal fixation of prestress type by the Weber technique and the osteosynthesis with Spongiosa-screw are the preponderant methods actually used in surgical treatment."} {"id": "PMID:1267683", "title": "Antibiotic prophylaxis in allo-arthroplastic hip joint surgery. Concentration assays in the wound exudate after parenteral administration of gentamicin.", "content": "The indecation and the efficacy of antibiotic prophylaxis in endoprosthetic operations are discussed with reference to prospective studies. After parenteral administration of 80 mg gentamicin the antibiotic concentrations in the serum and in the wound exudate were studied for 2 to 6 hrs after administration. During this observation period the gentamicin concentrations in the wound exudate were about equal to those in the serum. A comparison of the concentrations after parenteral and after local administration of gentamicin showed much higher concentrations in the wound exudate when gentamicin was administered with the bone cement.", "contents": "Antibiotic prophylaxis in allo-arthroplastic hip joint surgery. Concentration assays in the wound exudate after parenteral administration of gentamicin. The indecation and the efficacy of antibiotic prophylaxis in endoprosthetic operations are discussed with reference to prospective studies. After parenteral administration of 80 mg gentamicin the antibiotic concentrations in the serum and in the wound exudate were studied for 2 to 6 hrs after administration. During this observation period the gentamicin concentrations in the wound exudate were about equal to those in the serum. A comparison of the concentrations after parenteral and after local administration of gentamicin showed much higher concentrations in the wound exudate when gentamicin was administered with the bone cement."} {"id": "PMID:1267684", "title": "Acoustic reflex threshold measurement in hearing aid selection.", "content": "Aided speech discrimination scores were obtained for 18 patients with sensorineural hearing loss. Monosyllabic word discrimination lists with a competing message of connected discourse at a signal-to-noise ratio of +10 dB were used as the test stimuli, and measurements were made at four hearing aid gain settings for each subject. One of the gain settings was determined by measuring the acoustic reflex threshold for filtered noise in the ear contralateral to the aided ear. Two other settings were at +/- 10 dB relative to the reflex threshold gain setting; the fourth setting was determined with a traditional approach. Mean speech discrimination scores were highest at the reflex threshold gain setting and similar at the other three settings.", "contents": "Acoustic reflex threshold measurement in hearing aid selection. Aided speech discrimination scores were obtained for 18 patients with sensorineural hearing loss. Monosyllabic word discrimination lists with a competing message of connected discourse at a signal-to-noise ratio of +10 dB were used as the test stimuli, and measurements were made at four hearing aid gain settings for each subject. One of the gain settings was determined by measuring the acoustic reflex threshold for filtered noise in the ear contralateral to the aided ear. Two other settings were at +/- 10 dB relative to the reflex threshold gain setting; the fourth setting was determined with a traditional approach. Mean speech discrimination scores were highest at the reflex threshold gain setting and similar at the other three settings."} {"id": "PMID:1267685", "title": "Measurement of nasal air flow with a new apparatus.", "content": "An apparatus for measurement of nasal air flow has been calibrated against pressure-flow curves obtained in a pneumotachograph. A very high degree of correlation and an error of less than 3% of baseline values resulted when the apparatus was tested in hay fever patients using nasal allergen challenge.", "contents": "Measurement of nasal air flow with a new apparatus. An apparatus for measurement of nasal air flow has been calibrated against pressure-flow curves obtained in a pneumotachograph. A very high degree of correlation and an error of less than 3% of baseline values resulted when the apparatus was tested in hay fever patients using nasal allergen challenge."} {"id": "PMID:1267686", "title": "Postoperative deep vein thrombosis in otolaryngologic surgery.", "content": "The aim of this study was to determine the incidence of postoperative deep vein thrombosis in otolaryngologic surgery. The diagnosis was made by clinical examination, a method using fibrinogen labeled with radioactive iodine (125I), and the Doppler ultrasound technique. Only one (11%) patient developed an asymptomatic deep vein thrombosis. This is in contrast to the incidence in general surgical patients, which varies between 28% and 51%. The difference was probably related to the minimal tissue trauma and early mobilization of the otolaryngologic patients.", "contents": "Postoperative deep vein thrombosis in otolaryngologic surgery. The aim of this study was to determine the incidence of postoperative deep vein thrombosis in otolaryngologic surgery. The diagnosis was made by clinical examination, a method using fibrinogen labeled with radioactive iodine (125I), and the Doppler ultrasound technique. Only one (11%) patient developed an asymptomatic deep vein thrombosis. This is in contrast to the incidence in general surgical patients, which varies between 28% and 51%. The difference was probably related to the minimal tissue trauma and early mobilization of the otolaryngologic patients."} {"id": "PMID:1267687", "title": "Immediate and short-term complications of chronic ear surgery.", "content": "Complications of chronic ear surgery in a series of 2,192 operations are reported. Inadvertent opening of the inner ear occurred in 18 cases, leading to deafness in six ears. Four ears became deaf without apparent cause, for a total of ten (0.5%). High-tone sensorineural losses resulted in 3% of the ears. Facial nerve paralysis occurred in ten ears; in one of these, a graft was employed during primary surgery. All patients had a good recovery. It is stressed that to keep the number of complications at a minimum, strict rules must be followed and sufficient supervision offered in chronic ear surgery in teaching institutions.", "contents": "Immediate and short-term complications of chronic ear surgery. Complications of chronic ear surgery in a series of 2,192 operations are reported. Inadvertent opening of the inner ear occurred in 18 cases, leading to deafness in six ears. Four ears became deaf without apparent cause, for a total of ten (0.5%). High-tone sensorineural losses resulted in 3% of the ears. Facial nerve paralysis occurred in ten ears; in one of these, a graft was employed during primary surgery. All patients had a good recovery. It is stressed that to keep the number of complications at a minimum, strict rules must be followed and sufficient supervision offered in chronic ear surgery in teaching institutions."} {"id": "PMID:1267688", "title": "Electrophysiological study of Bell palsy: electrically elicited blink reflex in assessment of prognosis.", "content": "The electrically elicited blink reflex was tested serially in 81 patients with Bell palsy. In 56 patients, the reflex returned before excitability of the distal segment of the facial nerve was lost, indicating recovery of conduction across the involved segment before distal degeneration. These patients generally showed a good clinical recovery within a few months after onset. The reflex latency, however, was considerably prolonged during the first month, suggesting demyelination or other pathologic change. The reflex latency was reduced considerably during the second month and returned to normal levels during the third or fourth months. In the remaining 25 patients, direct response to facial nerve stimulation became unelicitable before reflex responses returned, indicating distal degeneration of the nerve. In this group of patients, clinical recovery was prolonged and generally incomplete.", "contents": "Electrophysiological study of Bell palsy: electrically elicited blink reflex in assessment of prognosis. The electrically elicited blink reflex was tested serially in 81 patients with Bell palsy. In 56 patients, the reflex returned before excitability of the distal segment of the facial nerve was lost, indicating recovery of conduction across the involved segment before distal degeneration. These patients generally showed a good clinical recovery within a few months after onset. The reflex latency, however, was considerably prolonged during the first month, suggesting demyelination or other pathologic change. The reflex latency was reduced considerably during the second month and returned to normal levels during the third or fourth months. In the remaining 25 patients, direct response to facial nerve stimulation became unelicitable before reflex responses returned, indicating distal degeneration of the nerve. In this group of patients, clinical recovery was prolonged and generally incomplete."} {"id": "PMID:1267689", "title": "Cysticercosis in otolaryngology.", "content": "Cysticercosis is not likely to be the first diagnosis the otologist has in mind when regarding tumors in the head and neck area. The fact that this disease may present a diagnostic and therapeutic problem is illustrated by three cases, appearing in the tongue, buccal mucosa, and midline of the neck, respectively. The local finding of a soft nontender mass, the typical calcifications in the soft tissues visible on roentgenograms, and the histopathological findings are described and illustrated. Attention is drawn to the fact that cerebral cysticercosis, which is a very grave disease, may cause tinnitus, nystagmus, and hearing disturbances.", "contents": "Cysticercosis in otolaryngology. Cysticercosis is not likely to be the first diagnosis the otologist has in mind when regarding tumors in the head and neck area. The fact that this disease may present a diagnostic and therapeutic problem is illustrated by three cases, appearing in the tongue, buccal mucosa, and midline of the neck, respectively. The local finding of a soft nontender mass, the typical calcifications in the soft tissues visible on roentgenograms, and the histopathological findings are described and illustrated. Attention is drawn to the fact that cerebral cysticercosis, which is a very grave disease, may cause tinnitus, nystagmus, and hearing disturbances."} {"id": "PMID:1267690", "title": "Audiologic profile of noise-induced hearing loss.", "content": "Audiologic results for 450 ears presumed to have uncomplicated noise induced hearing loss were analyzed to describe their typical profile and to quantify the characteristic audiometric notch. Data consisted of tonal and speech thresholds, speech discrimination scores, Bekesy tracings, and short increment sensitivity index scores, and tone decay at 4,000 hertz. In each case, the pattern of results indicated a cochlear site of lesion, although the only uniformly cochlear sign was the absence of a pattern of abnormal adaptation in Bekesy tracings. In each case, the audiogram could be approximated by a quartic equation. The mean difference between actual thresholds and those predicted by the best-fit quartic did not exceed 7.72 dB and was less than 5 dB for eight of the 11 frequencies for which comparisons were made. We propose the application of this characteristic to clinical practice and to automated hearing conservation programs.", "contents": "Audiologic profile of noise-induced hearing loss. Audiologic results for 450 ears presumed to have uncomplicated noise induced hearing loss were analyzed to describe their typical profile and to quantify the characteristic audiometric notch. Data consisted of tonal and speech thresholds, speech discrimination scores, Bekesy tracings, and short increment sensitivity index scores, and tone decay at 4,000 hertz. In each case, the pattern of results indicated a cochlear site of lesion, although the only uniformly cochlear sign was the absence of a pattern of abnormal adaptation in Bekesy tracings. In each case, the audiogram could be approximated by a quartic equation. The mean difference between actual thresholds and those predicted by the best-fit quartic did not exceed 7.72 dB and was less than 5 dB for eight of the 11 frequencies for which comparisons were made. We propose the application of this characteristic to clinical practice and to automated hearing conservation programs."} {"id": "PMID:1267691", "title": "Hearing loss in prosthetically treated adults with cleft palate.", "content": "The effect of obturator treatment of cleft palate on middle ear disease and hearing loss has not been established. This study serves as an otologic and audiologic review of a previously reported adult population with cleft palate. A substantial improvement in hearing levels subsequent to obturation was demonstrated; however, it was believed to be based on stabilization of pathologic features of the ear with age. A statistically significant correlation of hearing level with length of use of prosthesis or with type of lesion could not be demonstrated. Results are compared with those reported on the only other adult population with cleft palate. Prosthetic management of cleft palates is not shown to be detrimental, as has been generally thought.", "contents": "Hearing loss in prosthetically treated adults with cleft palate. The effect of obturator treatment of cleft palate on middle ear disease and hearing loss has not been established. This study serves as an otologic and audiologic review of a previously reported adult population with cleft palate. A substantial improvement in hearing levels subsequent to obturation was demonstrated; however, it was believed to be based on stabilization of pathologic features of the ear with age. A statistically significant correlation of hearing level with length of use of prosthesis or with type of lesion could not be demonstrated. Results are compared with those reported on the only other adult population with cleft palate. Prosthetic management of cleft palates is not shown to be detrimental, as has been generally thought."} {"id": "PMID:1267692", "title": "Outer hair cell loss and alterations in glycogen due to tobramycin sulfate.", "content": "A total of 26 albino guinea pigs were treated with 200 mg/kg/day of tobramycin sulfate. Animals were killed at various intervals of up to three weeks after seven days treatment. Outer hair cell (OHC) loss of the organ of Corti was evaluated by surface preparation techniques, and glycogen was assessed with PATCO- and PAS-stained sections. We have concluded that permanent damage of OHCs is most prevalent in areas that normally have the least amount and the smallest granule size of glycogen. With treatment, these susceptible areas are the least responsive in terms of an early increase in glycogen production. Furthermore, by 21 days after seven days of treatment, these same areas will reveal an almost total loss of glycogen at a time when damage is maximal.", "contents": "Outer hair cell loss and alterations in glycogen due to tobramycin sulfate. A total of 26 albino guinea pigs were treated with 200 mg/kg/day of tobramycin sulfate. Animals were killed at various intervals of up to three weeks after seven days treatment. Outer hair cell (OHC) loss of the organ of Corti was evaluated by surface preparation techniques, and glycogen was assessed with PATCO- and PAS-stained sections. We have concluded that permanent damage of OHCs is most prevalent in areas that normally have the least amount and the smallest granule size of glycogen. With treatment, these susceptible areas are the least responsive in terms of an early increase in glycogen production. Furthermore, by 21 days after seven days of treatment, these same areas will reveal an almost total loss of glycogen at a time when damage is maximal."} {"id": "PMID:1267693", "title": "Measurement of the acoustic reflex without a pressure seal.", "content": "Obtaining a hermetic seal in the external auditory canal is often a major obstacle in impedance audiometry. In the present study, the acoustic reflex threshold was determined for three groups of subjects, first with and then without a pressure-tight seal. It was found that for subjects with normal hearing or sensorineural hearing loss and normal tympanograms, 96% of the measurements obtained without a pressure seal were within 5 dB of those obtained with a seal. Among the subjects who exhibited negative middle ear pressure, the acoustic reflex could be measured consistently at the point of maximum compliance, while no response was observed without a pressure seal.", "contents": "Measurement of the acoustic reflex without a pressure seal. Obtaining a hermetic seal in the external auditory canal is often a major obstacle in impedance audiometry. In the present study, the acoustic reflex threshold was determined for three groups of subjects, first with and then without a pressure-tight seal. It was found that for subjects with normal hearing or sensorineural hearing loss and normal tympanograms, 96% of the measurements obtained without a pressure seal were within 5 dB of those obtained with a seal. Among the subjects who exhibited negative middle ear pressure, the acoustic reflex could be measured consistently at the point of maximum compliance, while no response was observed without a pressure seal."} {"id": "PMID:1267694", "title": "Yes-no test for nonorganic hearing loss.", "content": "The Yes-No Test is a procedure that can be used in the diagnosis of nonorganic hearing loss in children. The test employs a pure tone audiometric technique in which the child is instructed to say \"yes\" when he hears the tone and \"no\" when he does not hear the tone. This article describes clinical findings in three cases involving nonorganic hearing loss in which the Yes-No Test was instrumental in determining the true organic hearing thresholds.", "contents": "Yes-no test for nonorganic hearing loss. The Yes-No Test is a procedure that can be used in the diagnosis of nonorganic hearing loss in children. The test employs a pure tone audiometric technique in which the child is instructed to say \"yes\" when he hears the tone and \"no\" when he does not hear the tone. This article describes clinical findings in three cases involving nonorganic hearing loss in which the Yes-No Test was instrumental in determining the true organic hearing thresholds."} {"id": "PMID:1267695", "title": "Laryngeal injury: a critical review.", "content": "Thirty consecutive cases of laryngeal trauma requiring open exploration are reviewed. Eighteen injuries were the result of blunt trauma and 12 resulted from penetrating wounds. Within the blunt trauma group, eight of 18 injuries resulted in a competent airway and a good voice, six with a good airway but a fair voice, and four with airway compromise. Of 12 patients with penetrating wounds, ten sustained a good airway and a good voice, two a good airway and fair voice. Substantial granulation tissue response, though occurring in only eight of the 30 patients, was present in three of the four patients with airway stenosis. The use of a stent, in association with a soft tissue graft when mucosal loss cannot be approximated primarily, does not predispose to such a response, but rather facillitates maintenance of a competent skeletal framework and prevention of soft tissue endolaryngeal distortion.", "contents": "Laryngeal injury: a critical review. Thirty consecutive cases of laryngeal trauma requiring open exploration are reviewed. Eighteen injuries were the result of blunt trauma and 12 resulted from penetrating wounds. Within the blunt trauma group, eight of 18 injuries resulted in a competent airway and a good voice, six with a good airway but a fair voice, and four with airway compromise. Of 12 patients with penetrating wounds, ten sustained a good airway and a good voice, two a good airway and fair voice. Substantial granulation tissue response, though occurring in only eight of the 30 patients, was present in three of the four patients with airway stenosis. The use of a stent, in association with a soft tissue graft when mucosal loss cannot be approximated primarily, does not predispose to such a response, but rather facillitates maintenance of a competent skeletal framework and prevention of soft tissue endolaryngeal distortion."} {"id": "PMID:1267696", "title": "Neurilemomas of the infratemporal space: report of a case and review of the literature.", "content": "We describe a case of a trigeminal neurilemoma in an adolescent girl. It primarily involved the infratemporal space and extended into the middle cranial fossa, and began with only ocular symptoms. The surgical management is emphasized, illustrating the approach to the infratemporal fossa through a wide osteotomy of the coronoid process of the mandible without the need for mandibular split.", "contents": "Neurilemomas of the infratemporal space: report of a case and review of the literature. We describe a case of a trigeminal neurilemoma in an adolescent girl. It primarily involved the infratemporal space and extended into the middle cranial fossa, and began with only ocular symptoms. The surgical management is emphasized, illustrating the approach to the infratemporal fossa through a wide osteotomy of the coronoid process of the mandible without the need for mandibular split."} {"id": "PMID:1267697", "title": "Laryngeal spasm complicating pseudomyotonia.", "content": "Pseudomyotonia is a syndrome characterized by progressive muscle stiffness, weakness, myokymia, hyperhydrosis, and wasting of muscle. It especially affects the distal aspect of the extremities. The electromyogram is characteristic, and shows continuous muscle activity at rest. We discuss a case that is believed to be the first recorded instance of pseudomyotonia complicated by airway obstruction secondary to laryngeal spasm. Treatment with phenytoin sodium resulted in rapid improvement of the peripheral symptoms and simultaneous resolution of the laryngeal spasm.", "contents": "Laryngeal spasm complicating pseudomyotonia. Pseudomyotonia is a syndrome characterized by progressive muscle stiffness, weakness, myokymia, hyperhydrosis, and wasting of muscle. It especially affects the distal aspect of the extremities. The electromyogram is characteristic, and shows continuous muscle activity at rest. We discuss a case that is believed to be the first recorded instance of pseudomyotonia complicated by airway obstruction secondary to laryngeal spasm. Treatment with phenytoin sodium resulted in rapid improvement of the peripheral symptoms and simultaneous resolution of the laryngeal spasm."} {"id": "PMID:1267701", "title": "Bronchopulmonary levage to remove pulmonary casts and plugs.", "content": "Therapy for such obstructive pulmonary lung diseases as alveolar proteinosis, pneumonia, asthma, bronchiectasis, and cystic fibrosis, ranges from medical therapy to inhalation therapy to direct bronchoscopy and irrigation. The basic pathophysiologic feature is the retention of mucous secretions and foreign material within the lungs and therapy directed to removal of these secretions. Bronchopulmonary lavage recently has been suggested as an effective tool toward resolution of these illnesses. The otolaryngologist, who is adept in endoscopy, is asked to perform bronchoscopic procedures with washings to aid in the alleviation of these obstructive pulmonary diseases. This paper deals with the effectiveness of massive bronchopulmonary lavage in the elimination of severe chronic obstructive pulmonary lung diseases.", "contents": "Bronchopulmonary levage to remove pulmonary casts and plugs. Therapy for such obstructive pulmonary lung diseases as alveolar proteinosis, pneumonia, asthma, bronchiectasis, and cystic fibrosis, ranges from medical therapy to inhalation therapy to direct bronchoscopy and irrigation. The basic pathophysiologic feature is the retention of mucous secretions and foreign material within the lungs and therapy directed to removal of these secretions. Bronchopulmonary lavage recently has been suggested as an effective tool toward resolution of these illnesses. The otolaryngologist, who is adept in endoscopy, is asked to perform bronchoscopic procedures with washings to aid in the alleviation of these obstructive pulmonary diseases. This paper deals with the effectiveness of massive bronchopulmonary lavage in the elimination of severe chronic obstructive pulmonary lung diseases."} {"id": "PMID:1267702", "title": "Ventilating tubes in the middle ear.", "content": "One hundred children from 1 to 14 years of age had serous otitis media, the manifestations of which were bilateral in all but four patients. Thus, 196 ears were treated with aeration of the middle ear by means of a short transmyringeal tube. The mean duration of the treatment was 3.4 years, and the mean observation time was 7.3 years. Of the ears treated, 79.1% regained normal hearing, though scarring of the tympanic membrane and smaller adhesions were observed. The result was not satisfactory in 20.9% of the ears treated, the hearing losses varying from 25 to 60 dB. In 7.7% (15 ears) chronic otitis media developed; in 5.6% (11 of the 15 ears) cholesteatoma was confirmed surgically. Adhesive processes were present in 11.2%.", "contents": "Ventilating tubes in the middle ear. One hundred children from 1 to 14 years of age had serous otitis media, the manifestations of which were bilateral in all but four patients. Thus, 196 ears were treated with aeration of the middle ear by means of a short transmyringeal tube. The mean duration of the treatment was 3.4 years, and the mean observation time was 7.3 years. Of the ears treated, 79.1% regained normal hearing, though scarring of the tympanic membrane and smaller adhesions were observed. The result was not satisfactory in 20.9% of the ears treated, the hearing losses varying from 25 to 60 dB. In 7.7% (15 ears) chronic otitis media developed; in 5.6% (11 of the 15 ears) cholesteatoma was confirmed surgically. Adhesive processes were present in 11.2%."} {"id": "PMID:1267703", "title": "Electrodermal response, delayed auditory feedback, and lengthened off-time procedures. Comparison of use for medical-legal audiological assessment.", "content": "Results of conventional audiological procedures, lengthened off-time B\u00e9k\u00e9sy, and electrodermal response audiometry are compared with pure-tone delayed auditory feedback procedures for 100 subjects referred for medical-legal audiological evaluation. Specific attention is given to a new economical prototype unit for pure-tone delayed auditory feedback, to the comparison of results of special test procedures, and to the nonorganic hearing loss population.", "contents": "Electrodermal response, delayed auditory feedback, and lengthened off-time procedures. Comparison of use for medical-legal audiological assessment. Results of conventional audiological procedures, lengthened off-time B\u00e9k\u00e9sy, and electrodermal response audiometry are compared with pure-tone delayed auditory feedback procedures for 100 subjects referred for medical-legal audiological evaluation. Specific attention is given to a new economical prototype unit for pure-tone delayed auditory feedback, to the comparison of results of special test procedures, and to the nonorganic hearing loss population."} {"id": "PMID:1267704", "title": "Audiotympanometric findings in myasthenia gravis.", "content": "Myasthenia gravis can be a difficult diagnostic and therapeutic problem. Our study on six patients consisted of pure-tone audiograms, tympanometry, and acoustic reflex tests. Positive findings in the myasthenia gravis patients prior to medication included hyperacusis and increase in the intensity of sound required to elicit an acoustic reflex. Following medication, the hyperacusis lessened and the intensity of sound required to elicit the acoustic reflex decreased. During follow-up of two of the patients we encountered cholinergic (overdosage) crisis in one patient and myasthenic (underdosage) crisis in the other patient. Muscle weakness can be a common factor in both conditions. The acoustic reflex test can differentiate between the two types of crises. We believe audiotympanometric tests can aid in diagnosis and treatment of myasthenia gravis patients.", "contents": "Audiotympanometric findings in myasthenia gravis. Myasthenia gravis can be a difficult diagnostic and therapeutic problem. Our study on six patients consisted of pure-tone audiograms, tympanometry, and acoustic reflex tests. Positive findings in the myasthenia gravis patients prior to medication included hyperacusis and increase in the intensity of sound required to elicit an acoustic reflex. Following medication, the hyperacusis lessened and the intensity of sound required to elicit the acoustic reflex decreased. During follow-up of two of the patients we encountered cholinergic (overdosage) crisis in one patient and myasthenic (underdosage) crisis in the other patient. Muscle weakness can be a common factor in both conditions. The acoustic reflex test can differentiate between the two types of crises. We believe audiotympanometric tests can aid in diagnosis and treatment of myasthenia gravis patients."} {"id": "PMID:1267705", "title": "Hearing aid evaluation. Clinical experience with a new philosophy.", "content": "We report a new method of hearing aid evaluation with the underlying philosophy that evaluation of hearing aid performance is not an end in itself, but an integral part of the total rehabilitation of the hearing-impaired patient. This new method uses synthetic sentences and speech competition in varying \"message-to-competition ratios (MCRs)\" to evaluate patient performance with hearing aids. We report six illustrative cases and a follow-up survey of patient satisfaction with recommended hearing aids to relate our experience with this technique.", "contents": "Hearing aid evaluation. Clinical experience with a new philosophy. We report a new method of hearing aid evaluation with the underlying philosophy that evaluation of hearing aid performance is not an end in itself, but an integral part of the total rehabilitation of the hearing-impaired patient. This new method uses synthetic sentences and speech competition in varying \"message-to-competition ratios (MCRs)\" to evaluate patient performance with hearing aids. We report six illustrative cases and a follow-up survey of patient satisfaction with recommended hearing aids to relate our experience with this technique."} {"id": "PMID:1267706", "title": "Endolaryngeal cryosurgery. An improved technique.", "content": "Crysurgery is a tissue-destroying technique that has been difficult to use in the larynx except for small or superficial lesions. An improved technique for creating precise but large endolaryngeal lesions was developed and studied in dogs. Six animals each had one true vocal cord destroyed with a large closed cryoprobe introduced through a tracheostoma. The larynges were removed at intervals from four to 63 days and were examined grossly and histologically. This technique was found to be a safe and simple method for treating selected laryngeal neoplasms without external laryngeal surgery.", "contents": "Endolaryngeal cryosurgery. An improved technique. Crysurgery is a tissue-destroying technique that has been difficult to use in the larynx except for small or superficial lesions. An improved technique for creating precise but large endolaryngeal lesions was developed and studied in dogs. Six animals each had one true vocal cord destroyed with a large closed cryoprobe introduced through a tracheostoma. The larynges were removed at intervals from four to 63 days and were examined grossly and histologically. This technique was found to be a safe and simple method for treating selected laryngeal neoplasms without external laryngeal surgery."} {"id": "PMID:1267707", "title": "Lipomatous lesions of the parotid area.", "content": "Lipoma of the parotid gland is a rare lesion in adults and children, and appears most frequently in the fifth and sixth decades of life. Thirty-two lipomatous lesions of the parotid gland and periparotid area are reviewed. One lipoma occurred in a 7-year-old boy. The lesion shows a definite sex preference, with a male to female ratio of 10:1. The lesion shows no laterality preference. The most frequent preoperative diagnoses in our series were mixed tumor and Warthin tumor. In general, these lesions are soft, mobile, and painless and enlarge slowly. They are not associated with neurological deficits, skin changes, other salivary gland lesions, or with lipomas elsewhere in the body. The surgical management of this lesion should be the same as for any other parotid tumor with due regard for the presence of the facial nerve in the operative field. There were no facial nerve injuries in this series. If totally excised, these lesions show no tendency to recur.", "contents": "Lipomatous lesions of the parotid area. Lipoma of the parotid gland is a rare lesion in adults and children, and appears most frequently in the fifth and sixth decades of life. Thirty-two lipomatous lesions of the parotid gland and periparotid area are reviewed. One lipoma occurred in a 7-year-old boy. The lesion shows a definite sex preference, with a male to female ratio of 10:1. The lesion shows no laterality preference. The most frequent preoperative diagnoses in our series were mixed tumor and Warthin tumor. In general, these lesions are soft, mobile, and painless and enlarge slowly. They are not associated with neurological deficits, skin changes, other salivary gland lesions, or with lipomas elsewhere in the body. The surgical management of this lesion should be the same as for any other parotid tumor with due regard for the presence of the facial nerve in the operative field. There were no facial nerve injuries in this series. If totally excised, these lesions show no tendency to recur."} {"id": "PMID:1267708", "title": "Pachyonychia congenita with involvement of the larynx.", "content": "Pachyonychia congenita is a genetic syndrome of epithelial dysplasia that is inherited as an autosomal dominant trait. Its unique involvement within the larynx of a 3-year-old boy prompted this brief report of its clinical behavior and management.", "contents": "Pachyonychia congenita with involvement of the larynx. Pachyonychia congenita is a genetic syndrome of epithelial dysplasia that is inherited as an autosomal dominant trait. Its unique involvement within the larynx of a 3-year-old boy prompted this brief report of its clinical behavior and management."} {"id": "PMID:1267709", "title": "Removal of foreign bodies in the esophagus. An old device--a new procedure.", "content": "Extraction of hard, spherical foreign bodies from the esophagus has been accomplished with the use of a Dormia basket in combination with esophagoscopy. The Dormia basket was originally designed for the extraction of stones from the urinary tract.", "contents": "Removal of foreign bodies in the esophagus. An old device--a new procedure. Extraction of hard, spherical foreign bodies from the esophagus has been accomplished with the use of a Dormia basket in combination with esophagoscopy. The Dormia basket was originally designed for the extraction of stones from the urinary tract."} {"id": "PMID:1267710", "title": "Malignant melanoma of the head and neck in children. Review of the literature and report of a case.", "content": "Perusal of the literature revealed that until 1970, 13 children with malignant melanoma of the head and neck had been reported. This group includes two cases of melanoma that developed in a giant cell nevus, as well as one case of congenital melanoma. The biologic features of prepubertal melanoma appear basically analogous to those of the adult variety. Malignant melanoma of the auricle is described in a 2 1/2-year-old child. Surgical therapy was given, and BCG vaccination was used as an adjuvant. The patient is alive and free of signs of the disease 2 1/2 years following the operation. This appears to be the third reported case of malignant melanoma of the external ear in a child.", "contents": "Malignant melanoma of the head and neck in children. Review of the literature and report of a case. Perusal of the literature revealed that until 1970, 13 children with malignant melanoma of the head and neck had been reported. This group includes two cases of melanoma that developed in a giant cell nevus, as well as one case of congenital melanoma. The biologic features of prepubertal melanoma appear basically analogous to those of the adult variety. Malignant melanoma of the auricle is described in a 2 1/2-year-old child. Surgical therapy was given, and BCG vaccination was used as an adjuvant. The patient is alive and free of signs of the disease 2 1/2 years following the operation. This appears to be the third reported case of malignant melanoma of the external ear in a child."} {"id": "PMID:1267711", "title": "Gustatory rhinorrhea developing after radical parotidectomy-a new syndrome?", "content": "We report a case in which a 76-year-old woman developed unilateral gustatory rhinorrhea on the operated side after a radical parotidectomy. This is believed to be a new and previously unreported phenomenon that is mechanistically similar to the Frye syndrome (gustatory sweating).", "contents": "Gustatory rhinorrhea developing after radical parotidectomy-a new syndrome? We report a case in which a 76-year-old woman developed unilateral gustatory rhinorrhea on the operated side after a radical parotidectomy. This is believed to be a new and previously unreported phenomenon that is mechanistically similar to the Frye syndrome (gustatory sweating)."} {"id": "PMID:1267715", "title": "Prostaglandins in middle ear effusions.", "content": "Although otitis media with effusion is usually a self-limiting disease, there are certain cases in which there appears to be chronic progression of the disease with serious sequelae. It has been demonstrated that there are biological mediators of inflammation in the middle ear that are capable of producing mucous membrane pathologic features. Some of these mediators of inflammation may be the prostaglandins. These cyclic fatty acids have been found in ten consecutive middle ear fluids in concentrations that are usually higher than the corresponding serum or plasma. It is suggested that prostaglandins may play an active role in maintaining the inflammatory response in the middle ear in otitis media with effusion.", "contents": "Prostaglandins in middle ear effusions. Although otitis media with effusion is usually a self-limiting disease, there are certain cases in which there appears to be chronic progression of the disease with serious sequelae. It has been demonstrated that there are biological mediators of inflammation in the middle ear that are capable of producing mucous membrane pathologic features. Some of these mediators of inflammation may be the prostaglandins. These cyclic fatty acids have been found in ten consecutive middle ear fluids in concentrations that are usually higher than the corresponding serum or plasma. It is suggested that prostaglandins may play an active role in maintaining the inflammatory response in the middle ear in otitis media with effusion."} {"id": "PMID:1267716", "title": "Causes of recurrent laryngeal nerve paralysis.", "content": "The recurrent laryngeal nerve in its course from the brain stem to the larynx follows a path that brings it in proximity to numerous structures. These structures can interfere with its function by pressure or by disruption of the nerve caused by disease invading the nerve. The various causes of recurrent laryngeal nerve paralysis that I have observed during the past 24 years are reported. In 134 patients with recurrent laryngeal nerve paralysis, the left recurrent nerve was most commonly involved. Malignant neoplasms of the lung and pulmonary tuberculosis were the most frequent causes of the paralysis.", "contents": "Causes of recurrent laryngeal nerve paralysis. The recurrent laryngeal nerve in its course from the brain stem to the larynx follows a path that brings it in proximity to numerous structures. These structures can interfere with its function by pressure or by disruption of the nerve caused by disease invading the nerve. The various causes of recurrent laryngeal nerve paralysis that I have observed during the past 24 years are reported. In 134 patients with recurrent laryngeal nerve paralysis, the left recurrent nerve was most commonly involved. Malignant neoplasms of the lung and pulmonary tuberculosis were the most frequent causes of the paralysis."} {"id": "PMID:1267717", "title": "Cranial polyneuritis and Bell palsy.", "content": "In view of the specific nature of the clinical and neurologic findings in Bell palsy and other acute benign cranial neuritides, the neural component of cutaneous herpes simplex, the predilection of the herpesvirus for sensory nerves, and intrinsic behavior and immunologic interreactions of the herpesvirus within ganglion cells, it is suggested that (1) the entity that has been termed \"idiopathic facial paralysis\" be recognized as an acute benign cranial polyneuritis; and (2) other acute benign cranial neuritides be recognized as formes frustes of Bell palsy.", "contents": "Cranial polyneuritis and Bell palsy. In view of the specific nature of the clinical and neurologic findings in Bell palsy and other acute benign cranial neuritides, the neural component of cutaneous herpes simplex, the predilection of the herpesvirus for sensory nerves, and intrinsic behavior and immunologic interreactions of the herpesvirus within ganglion cells, it is suggested that (1) the entity that has been termed \"idiopathic facial paralysis\" be recognized as an acute benign cranial polyneuritis; and (2) other acute benign cranial neuritides be recognized as formes frustes of Bell palsy."} {"id": "PMID:1267718", "title": "Functional anatomy of tensor palati and levator palati muscles.", "content": "An experimental study of the modus operandi of tensor and levator palati muscles over the Eustachian tube was conducted in two dogs. The tensor palati muscle is divisible into four functional units: (1) anterior part, vertical fibers; (2) middle part, oblique fibers; (3) posterior part, horizontal fibers; and (4) posterior-most part, osseous origin. Though the levator palati passively fixes the medial lamina and narrows the pharyngeal ostium, it dilates the lumen of the isthmus by two mechanisms: (1) rectification of the isthmus \"kink\" by bringing the cartilaginous and osseous segments into a stright line; and (2) pushing away the surrounding soft tissue pressure that is being exerted over the medial wall of the tube (not protected by cartilage). The peculiar absence of the medial cartilaginous lamina near the isthmus is attributed to the following: (1) freedom of movement of cartilaginous tube; (2) better anchorage of tubal cartilage passively by levator palati; (3) \"kinking\" of canal; and (4) compression of the lumen.", "contents": "Functional anatomy of tensor palati and levator palati muscles. An experimental study of the modus operandi of tensor and levator palati muscles over the Eustachian tube was conducted in two dogs. The tensor palati muscle is divisible into four functional units: (1) anterior part, vertical fibers; (2) middle part, oblique fibers; (3) posterior part, horizontal fibers; and (4) posterior-most part, osseous origin. Though the levator palati passively fixes the medial lamina and narrows the pharyngeal ostium, it dilates the lumen of the isthmus by two mechanisms: (1) rectification of the isthmus \"kink\" by bringing the cartilaginous and osseous segments into a stright line; and (2) pushing away the surrounding soft tissue pressure that is being exerted over the medial wall of the tube (not protected by cartilage). The peculiar absence of the medial cartilaginous lamina near the isthmus is attributed to the following: (1) freedom of movement of cartilaginous tube; (2) better anchorage of tubal cartilage passively by levator palati; (3) \"kinking\" of canal; and (4) compression of the lumen."} {"id": "PMID:1267719", "title": "Patulous Eustachian tube. A new treatment with infusion of absorbable gelatin sponge solution.", "content": "For the treatment of abnormally patent Eustachian tube, we had previously employed repeated tubal insufflation of salicylic acid-boric powder (1:4) through a Eustachian tube catheter. Such treatments, however, usually were associated with uncertain results and numerous complications. Therefore, treatment of this condition was changed to employment of an infusion of absorbable gelatin sponge solution directly into the Eustachian tube. Twenty-two ears in 16 patients recovered successfully when this method was used.", "contents": "Patulous Eustachian tube. A new treatment with infusion of absorbable gelatin sponge solution. For the treatment of abnormally patent Eustachian tube, we had previously employed repeated tubal insufflation of salicylic acid-boric powder (1:4) through a Eustachian tube catheter. Such treatments, however, usually were associated with uncertain results and numerous complications. Therefore, treatment of this condition was changed to employment of an infusion of absorbable gelatin sponge solution directly into the Eustachian tube. Twenty-two ears in 16 patients recovered successfully when this method was used."} {"id": "PMID:1267720", "title": "Vocal cord fixation in laryngeal carcinoma.", "content": "The 1962 TNM classification (T, tumor and extent; N, regional lymph node metastasis, M, distant metastasis) did not emphasize vocal cord fixation in staging. In the revision of 1972, lesions with partial fixation were classified T2, stage II, and those causing fixation were T3, stage III. The therapeutic results in 39 patients with fixed cords revealed a determinante five-year survival of 41% and an absolute of 23%. These statistics support the validity of the 1972 classification. Careful evaluation of vocal cord mobility prior to selection of therapy is stressed.", "contents": "Vocal cord fixation in laryngeal carcinoma. The 1962 TNM classification (T, tumor and extent; N, regional lymph node metastasis, M, distant metastasis) did not emphasize vocal cord fixation in staging. In the revision of 1972, lesions with partial fixation were classified T2, stage II, and those causing fixation were T3, stage III. The therapeutic results in 39 patients with fixed cords revealed a determinante five-year survival of 41% and an absolute of 23%. These statistics support the validity of the 1972 classification. Careful evaluation of vocal cord mobility prior to selection of therapy is stressed."} {"id": "PMID:1267721", "title": "Oscilloscopic analysis of the stapedius muscle reflex in brain stem lesions.", "content": "An oscilloscopic analysis of several features of the stapedius muscle reflex was carried out in a group of normal subjects and in patients affected by dysfunction at the brain stem level due to a pathologic lesion or temporary reduction by small doses of barbiturates. Under these conditions, the increased latency and reduced amplitude of the reflex, but particularly the reduced velocity and, not infrequently, the step-like pattern of the tracings, are considered to be data of considerable value in disorders of the brain stem structues.", "contents": "Oscilloscopic analysis of the stapedius muscle reflex in brain stem lesions. An oscilloscopic analysis of several features of the stapedius muscle reflex was carried out in a group of normal subjects and in patients affected by dysfunction at the brain stem level due to a pathologic lesion or temporary reduction by small doses of barbiturates. Under these conditions, the increased latency and reduced amplitude of the reflex, but particularly the reduced velocity and, not infrequently, the step-like pattern of the tracings, are considered to be data of considerable value in disorders of the brain stem structues."} {"id": "PMID:1267722", "title": "Pseudosarcomas of the pharynx and larynx.", "content": "Pseudosarcoma of the pharynx and larynx has remained an enigma both to the pathologist and clinician since its original description by Lane in 1957. These lesions are usually polypoid growths that microscopically present very bizarre appearances beneath a squamous cell carcinoma. Eight cases of pseudosarcoma of the larynxand pharynx were observed. These occurred almost twice as often in males as females, with an average age of 56 years. Most were extralaryngeal lesions, and in all cases surgical excision was the primary therapeutic modality. A thorough review of the literature summarizes the clinical and pathologic characteristics of these lesions. There is strong clinical evidence against the traditional belief of the benign course of these lesions, and we recommend that they be treated aggresively like any other carcinoma of the head and neck.", "contents": "Pseudosarcomas of the pharynx and larynx. Pseudosarcoma of the pharynx and larynx has remained an enigma both to the pathologist and clinician since its original description by Lane in 1957. These lesions are usually polypoid growths that microscopically present very bizarre appearances beneath a squamous cell carcinoma. Eight cases of pseudosarcoma of the larynxand pharynx were observed. These occurred almost twice as often in males as females, with an average age of 56 years. Most were extralaryngeal lesions, and in all cases surgical excision was the primary therapeutic modality. A thorough review of the literature summarizes the clinical and pathologic characteristics of these lesions. There is strong clinical evidence against the traditional belief of the benign course of these lesions, and we recommend that they be treated aggresively like any other carcinoma of the head and neck."} {"id": "PMID:1267723", "title": "Neonatal screening for detection of deafness.", "content": "To assess various methods of early detection of deafness, a longtudinal study of infants born in the Jerusalem area was performed. The 17,731 newborns were tested by an acoustic signal generator hearing test (Apriton), and the \"at risk\" for deafness register was applied to them. Twenty-five children were identified as deaf, 14 with severe or profound hearing loss and 11 with moderate or moderately severe loss. The screening hearing test did not prove to be sensitive enough for detection of deafness in newborns, and, therefore, is not considered valid for screening purposes. The at risk for deafness register, which in our program covered 20% of the entire newborn population, proved to be to expensive and impractical; a restricted register, including approximately 7% of the newborns, is suggested.", "contents": "Neonatal screening for detection of deafness. To assess various methods of early detection of deafness, a longtudinal study of infants born in the Jerusalem area was performed. The 17,731 newborns were tested by an acoustic signal generator hearing test (Apriton), and the \"at risk\" for deafness register was applied to them. Twenty-five children were identified as deaf, 14 with severe or profound hearing loss and 11 with moderate or moderately severe loss. The screening hearing test did not prove to be sensitive enough for detection of deafness in newborns, and, therefore, is not considered valid for screening purposes. The at risk for deafness register, which in our program covered 20% of the entire newborn population, proved to be to expensive and impractical; a restricted register, including approximately 7% of the newborns, is suggested."} {"id": "PMID:1267724", "title": "Myxomas of the head and neck.", "content": "Myxomas are benign mesenchymal tumors that occur rarely in the head and neck. When they do occur, they are prevalent in the jaws and occur less frequently in the subcutaneous tissues. We report ten new cases and review the clinical, structural, and behavioral characteristics of myxomas arising in various head and neck locations. All ages are affected. The most common initial complaint is the presence of a slow-growing mass. The sarcomas, especially liposarcomas and fibrosarcomas, rank high in the differential diagnosis of myxomas. These tumors are stubborn infiltrators. When a capsule is present, it is usually incomplete and insufficient to contain the tumor. Treatment is by wide surgical excision. The high recurrence rate previously reported is probably due to incomplete excision and is higher when enucleation or curettage are used. Long-term follow-up is mandatory since recurrences may develop several years after treatment.", "contents": "Myxomas of the head and neck. Myxomas are benign mesenchymal tumors that occur rarely in the head and neck. When they do occur, they are prevalent in the jaws and occur less frequently in the subcutaneous tissues. We report ten new cases and review the clinical, structural, and behavioral characteristics of myxomas arising in various head and neck locations. All ages are affected. The most common initial complaint is the presence of a slow-growing mass. The sarcomas, especially liposarcomas and fibrosarcomas, rank high in the differential diagnosis of myxomas. These tumors are stubborn infiltrators. When a capsule is present, it is usually incomplete and insufficient to contain the tumor. Treatment is by wide surgical excision. The high recurrence rate previously reported is probably due to incomplete excision and is higher when enucleation or curettage are used. Long-term follow-up is mandatory since recurrences may develop several years after treatment."} {"id": "PMID:1267725", "title": "Pneumocele of the maxillary sinus. Report of a case.", "content": "The first two cases of pneumocele of the maxillary sinus have been recently published. The expanded antrum produced a different initial complaint in each case. A third case, with yet another initial problem, middle ear effusion, is now reported. The roentgenographic and operative findings and the therapeutic effect of decompression by antrostomy would suggest that this is a specific disease entity, presumably due to a check valve obstruction of the sinus ostium.", "contents": "Pneumocele of the maxillary sinus. Report of a case. The first two cases of pneumocele of the maxillary sinus have been recently published. The expanded antrum produced a different initial complaint in each case. A third case, with yet another initial problem, middle ear effusion, is now reported. The roentgenographic and operative findings and the therapeutic effect of decompression by antrostomy would suggest that this is a specific disease entity, presumably due to a check valve obstruction of the sinus ostium."} {"id": "PMID:1267726", "title": "Rhinosporidiosis.", "content": "A case of nasal rhinosporidiosis occurred in a 73-year-old man who has lived all his life in the United States. The lesion was treated surgically, and he remains free of disease four years later.", "contents": "Rhinosporidiosis. A case of nasal rhinosporidiosis occurred in a 73-year-old man who has lived all his life in the United States. The lesion was treated surgically, and he remains free of disease four years later."} {"id": "PMID:1267727", "title": "Goldenhar syndrome. Associated with submandibular gland hyperplasia and hemihypoplasia of the mobile tongue.", "content": "We report of a case of Goldenhar syndrome with submandibular gland hyperplasia and hemihypoplasia of the mobile tongue. This association has not been noted in the literature. A vascular abnormality or hemorrhagic phenomenon occurring during embryogenesis have been proposed as an explanation for the spectrum of defects seen in this syndrome. Congenitae hearing loss, when it occurs in Goldenhar syndrome, is usually unilateral and conductive in nature; however, inner ear defects may be more common than previously recognized.", "contents": "Goldenhar syndrome. Associated with submandibular gland hyperplasia and hemihypoplasia of the mobile tongue. We report of a case of Goldenhar syndrome with submandibular gland hyperplasia and hemihypoplasia of the mobile tongue. This association has not been noted in the literature. A vascular abnormality or hemorrhagic phenomenon occurring during embryogenesis have been proposed as an explanation for the spectrum of defects seen in this syndrome. Congenitae hearing loss, when it occurs in Goldenhar syndrome, is usually unilateral and conductive in nature; however, inner ear defects may be more common than previously recognized."} {"id": "PMID:1267730", "title": "Cardiac monitoring during exercise tests in the horse. 2. Heart rate responses to exercise.", "content": "Data on resting heart rates, pre-exercise heart rates, the anticipatory rises before exercise, the influence of speed of work and recovery heart rates have been presented. Some observations on differences in the heart rate response on slow and fast working days are also recorded. In conformity with other workers, a linear relationship between heart rate and working speed within the range of 400-800 metre/min was observed. When the speed of work was between 400-800 metre/min, horses with resting ECG's classed as abnormal had significantly higher heart rates than those regarded as normal. It was also observed that the abnormal animals showed lower heart rates than a small number classed as borderline. The significance of these findings is discussed and the need for further work indicated.", "contents": "Cardiac monitoring during exercise tests in the horse. 2. Heart rate responses to exercise. Data on resting heart rates, pre-exercise heart rates, the anticipatory rises before exercise, the influence of speed of work and recovery heart rates have been presented. Some observations on differences in the heart rate response on slow and fast working days are also recorded. In conformity with other workers, a linear relationship between heart rate and working speed within the range of 400-800 metre/min was observed. When the speed of work was between 400-800 metre/min, horses with resting ECG's classed as abnormal had significantly higher heart rates than those regarded as normal. It was also observed that the abnormal animals showed lower heart rates than a small number classed as borderline. The significance of these findings is discussed and the need for further work indicated."} {"id": "PMID:1267731", "title": "Osteodystrophia fibrosa in horses at pasture in Queensland: field and laboratory observations.", "content": "Horses grazing manily Cenchrus ciliaris and/or Panicum maximum var. trichoglume pastures on over 30 properties in southern central Queensland developed lesions of osteodystrophia fibrosa. Horses on individual properties in coastal Queensland grazing Setaria anceps, Brachiaria mutica or Pennisetum clandestinum also developed the disease. Ill-thrift, lameness, and fibrous swellings of nasal bones, maxillae and mandibles were observed. Calcium and phosphorus levels of pasture were normal but all the above pasture species contained oxalates which were suspected of causing the disease.", "contents": "Osteodystrophia fibrosa in horses at pasture in Queensland: field and laboratory observations. Horses grazing manily Cenchrus ciliaris and/or Panicum maximum var. trichoglume pastures on over 30 properties in southern central Queensland developed lesions of osteodystrophia fibrosa. Horses on individual properties in coastal Queensland grazing Setaria anceps, Brachiaria mutica or Pennisetum clandestinum also developed the disease. Ill-thrift, lameness, and fibrous swellings of nasal bones, maxillae and mandibles were observed. Calcium and phosphorus levels of pasture were normal but all the above pasture species contained oxalates which were suspected of causing the disease."} {"id": "PMID:1267732", "title": "Squamous-cell carcinoma of the vulva in Merino sheep.", "content": "Squamous-cell carcinoma of the vulva was observed in 3.1% of Merino ewes up to 3 years old. It is suggested that this high incidence of tumours was related to increased exposure of the perineal region to direct sunlight. It occurred in a group of sheep where short docking of tails and a radical surgical procedure to reduce cutaneous myiasis (Mules' operation) both led to greater exposure of the perineal region. The perineum was also subject to scarring from the operation and to application of organophosphate compounds to control cutaneous myiasis.", "contents": "Squamous-cell carcinoma of the vulva in Merino sheep. Squamous-cell carcinoma of the vulva was observed in 3.1% of Merino ewes up to 3 years old. It is suggested that this high incidence of tumours was related to increased exposure of the perineal region to direct sunlight. It occurred in a group of sheep where short docking of tails and a radical surgical procedure to reduce cutaneous myiasis (Mules' operation) both led to greater exposure of the perineal region. The perineum was also subject to scarring from the operation and to application of organophosphate compounds to control cutaneous myiasis."} {"id": "PMID:1267733", "title": "Piroplasmosis in buffaloes and its serological diagnosis based on a homology between buffalo and bovine immunoglobulins.", "content": "Babesia argentina, Babesia bigemina and Theileria mutans were transmitted experimentally from water buffaloes (Bubalus bubalis) to splenectomised Bos taurus calves. Buffaloes were positive to an indirect fluorescent antibody test for B. argentina when reagents of bovine origin were used. The formation of similar patterns during immunoelectrophoresis suggested a homology of buffalo and bovine serum proteins, particularly IgG.", "contents": "Piroplasmosis in buffaloes and its serological diagnosis based on a homology between buffalo and bovine immunoglobulins. Babesia argentina, Babesia bigemina and Theileria mutans were transmitted experimentally from water buffaloes (Bubalus bubalis) to splenectomised Bos taurus calves. Buffaloes were positive to an indirect fluorescent antibody test for B. argentina when reagents of bovine origin were used. The formation of similar patterns during immunoelectrophoresis suggested a homology of buffalo and bovine serum proteins, particularly IgG."} {"id": "PMID:1267737", "title": "Assortative mating in lesser snow geese (Anser caerulescens).", "content": "Assortative mating occurs in the dimorphic lesser snow geese in the wild. Mixed matings between the blue and white phases are much less frequent than would be expected by chance. Evidence from marked birds in field conditions indicated that mate choice was correlated with familial color. Birds from white families usually chose white mates, birds from blue families usually chose blue mates, and birds from mixed families chose mates of either color. Similar results were obtained under captive conditions when offspring from foster families with particular parental and offspring color combinations were allowed to choose mates. Both parental color and sibling color appeared to influence mate choice. The bird's own color did not appear to be important in mate choice in either field or experimental conditions, and in those cases where male and female parents differed in color neither parental color was more influential than the other in determining offspring mate choice. The results provide the first evidence, to our knowledge, that mate selection based on familial appearance operates intraspecifically in the wild.", "contents": "Assortative mating in lesser snow geese (Anser caerulescens). Assortative mating occurs in the dimorphic lesser snow geese in the wild. Mixed matings between the blue and white phases are much less frequent than would be expected by chance. Evidence from marked birds in field conditions indicated that mate choice was correlated with familial color. Birds from white families usually chose white mates, birds from blue families usually chose blue mates, and birds from mixed families chose mates of either color. Similar results were obtained under captive conditions when offspring from foster families with particular parental and offspring color combinations were allowed to choose mates. Both parental color and sibling color appeared to influence mate choice. The bird's own color did not appear to be important in mate choice in either field or experimental conditions, and in those cases where male and female parents differed in color neither parental color was more influential than the other in determining offspring mate choice. The results provide the first evidence, to our knowledge, that mate selection based on familial appearance operates intraspecifically in the wild."} {"id": "PMID:1267738", "title": "Cerebral lateralization and spatial ability.", "content": "Frequencies of three cerebral dominance genotypes who show right or left ear superiority on a verbal dichotic listening test and left or right field superiority on a tachistoscopic lateral field test of perceptual dominance are deduced. A hypothesis is offered relating direction of cerebral dominance, as defined by genotype, to degree of lateral specialization and perceptual ability, and a theoretical distribution of subjects according to spatial-perceptual ability and lateralization is derived. This distribution corresponds almost exactly with empirical data, thus confirming the proposed correlation between lateralization and spatial-perceptual capacity.", "contents": "Cerebral lateralization and spatial ability. Frequencies of three cerebral dominance genotypes who show right or left ear superiority on a verbal dichotic listening test and left or right field superiority on a tachistoscopic lateral field test of perceptual dominance are deduced. A hypothesis is offered relating direction of cerebral dominance, as defined by genotype, to degree of lateral specialization and perceptual ability, and a theoretical distribution of subjects according to spatial-perceptual ability and lateralization is derived. This distribution corresponds almost exactly with empirical data, thus confirming the proposed correlation between lateralization and spatial-perceptual capacity."} {"id": "PMID:1267739", "title": "Editorial: Myocardial sarcomeres and the functioning mammalian heart.", "content": "Previously the length-tension properties of the isolated papillary muscle have been related to myocardial sarcomere lengths. Though past studies have relied upon fixed material, recentlly, living muscles have been used. Sarcomere lengths have now been measured on the same specimens in both living and fixed material and the sarcomere length at optimum muscle length established. These lengths are extremely uniform. Studies on the sarcomere lengths through the wall of the left ventricle have also been carried out. Surprisingly sarcomere lengths were relatively uniform from endocardium to epicardium over a wide range of intraventricular pressures. Furthermore, enddiastolic sacarcomere lengths were 91% to 94% of optimum sarcomere length over a physiologic pressure range. Since the papillary muscle in function has been shown to shorten by 23% (to 70% of optimum sarcomere length), these results suggest that the papillary muscle uses the entire ascending limb of the length-tension curve during function.", "contents": "Editorial: Myocardial sarcomeres and the functioning mammalian heart. Previously the length-tension properties of the isolated papillary muscle have been related to myocardial sarcomere lengths. Though past studies have relied upon fixed material, recentlly, living muscles have been used. Sarcomere lengths have now been measured on the same specimens in both living and fixed material and the sarcomere length at optimum muscle length established. These lengths are extremely uniform. Studies on the sarcomere lengths through the wall of the left ventricle have also been carried out. Surprisingly sarcomere lengths were relatively uniform from endocardium to epicardium over a wide range of intraventricular pressures. Furthermore, enddiastolic sacarcomere lengths were 91% to 94% of optimum sarcomere length over a physiologic pressure range. Since the papillary muscle in function has been shown to shorten by 23% (to 70% of optimum sarcomere length), these results suggest that the papillary muscle uses the entire ascending limb of the length-tension curve during function."} {"id": "PMID:1267740", "title": "[Hemodynamics and myocardial contractility in experimental tourniquet-shock].", "content": "A reproducible tourniquet-shock has been produced in hind limbs of dogs by unilateral and bilateral extremity ischemia. The following parameters have been measured for analysing the function of the cardiovascular system: mean aortic pressure, heart rate, cardiac output, intraventricular pressure and left ventricular pressure. From these data the stroke volume, stroke work, total peripheral resistance and the parameters of heart contractility dp/dtmax, dp/dtmax:IP and t-dp/dtmax were derived. During the ischemic period all circulatory parameters did not change in comparison to the controls. A tourniquet-shock developed upon recirculation of the ischemically stressed extremity which was more pronounced after bilateral than after unilateral hind leg ischemia. After release of the tourniquet all animals with unilateral tourniquet survived an observation period of 5 hours duration, whereas 6 out of 8 dogs with bilateral tourniquet died of heart failure. Upon release of the tourniquet, the cardiac output raised up to 140% of the normal value: the abruptly decreasing aortic pressure was fully compensated by a tachycardia from 100 to 190 (beats/minute). The parameters dp/dtmax:IP and t-dp/dtmax indicated a distinct increase of the left ventricular contractility in the early tourniquet-syndrom. Already after 30 minutes an increasing circulatory depression developed indicative of the decrease in aortic pressure, and enddiastolic pressure. At the same time an increase of heart rate and total peripheral resistance occurred. The parameters of left ventricular contractility did not change markedly during the course of shock except for the final stage.", "contents": "[Hemodynamics and myocardial contractility in experimental tourniquet-shock]. A reproducible tourniquet-shock has been produced in hind limbs of dogs by unilateral and bilateral extremity ischemia. The following parameters have been measured for analysing the function of the cardiovascular system: mean aortic pressure, heart rate, cardiac output, intraventricular pressure and left ventricular pressure. From these data the stroke volume, stroke work, total peripheral resistance and the parameters of heart contractility dp/dtmax, dp/dtmax:IP and t-dp/dtmax were derived. During the ischemic period all circulatory parameters did not change in comparison to the controls. A tourniquet-shock developed upon recirculation of the ischemically stressed extremity which was more pronounced after bilateral than after unilateral hind leg ischemia. After release of the tourniquet all animals with unilateral tourniquet survived an observation period of 5 hours duration, whereas 6 out of 8 dogs with bilateral tourniquet died of heart failure. Upon release of the tourniquet, the cardiac output raised up to 140% of the normal value: the abruptly decreasing aortic pressure was fully compensated by a tachycardia from 100 to 190 (beats/minute). The parameters dp/dtmax:IP and t-dp/dtmax indicated a distinct increase of the left ventricular contractility in the early tourniquet-syndrom. Already after 30 minutes an increasing circulatory depression developed indicative of the decrease in aortic pressure, and enddiastolic pressure. At the same time an increase of heart rate and total peripheral resistance occurred. The parameters of left ventricular contractility did not change markedly during the course of shock except for the final stage."} {"id": "PMID:1267741", "title": "Continuous recording of local myocardial function in normal and ischemic myocardium.", "content": "Experiments in anaesthetized open chest dogs are described in which intramyocardial pressure was determined by two methods, both suitable for long time experiments. By means of a Fogarty catheter in connection with a normal transducer the intramyocardial pressure can be measured. With this method the pressure gradient from epicardial to endocardial muscle layers is demonstrated. Insertion of catheter tip manometers leads only to small trauma of the myocardium. This method allows the determination of systolic and enddiastolic tissue pressure together with the dp/dtmax and dp/dtmin. Measurements were performed in normal and in ischemic areas of the myocardium. In the ischemic parts of the myocardium all parameters descline, while in the normal, non ischemic areas the parameters increase, thus demonstrating overactivity, which compensates for the loss of myocardial function in the ischemic parts. The overall function of the heart as a pump remains nearly unaffected. On release of the coronary ligature the negative changes in the ischemic myocardium are rapidly restored. During the phase of reactive hyperemia the parameters measured in the ischemic area even increase above the control values.", "contents": "Continuous recording of local myocardial function in normal and ischemic myocardium. Experiments in anaesthetized open chest dogs are described in which intramyocardial pressure was determined by two methods, both suitable for long time experiments. By means of a Fogarty catheter in connection with a normal transducer the intramyocardial pressure can be measured. With this method the pressure gradient from epicardial to endocardial muscle layers is demonstrated. Insertion of catheter tip manometers leads only to small trauma of the myocardium. This method allows the determination of systolic and enddiastolic tissue pressure together with the dp/dtmax and dp/dtmin. Measurements were performed in normal and in ischemic areas of the myocardium. In the ischemic parts of the myocardium all parameters descline, while in the normal, non ischemic areas the parameters increase, thus demonstrating overactivity, which compensates for the loss of myocardial function in the ischemic parts. The overall function of the heart as a pump remains nearly unaffected. On release of the coronary ligature the negative changes in the ischemic myocardium are rapidly restored. During the phase of reactive hyperemia the parameters measured in the ischemic area even increase above the control values."} {"id": "PMID:1267742", "title": "[A slide ruler and nomogram for calculations in cumulation kinetics of cardiac glycosides (author's transl)].", "content": "1. Substance I, whose elimination we can approximate with an exponential function, is active in the organism. 2. At a given moment substance II with the same onset of action whose elimination we also can approximate with an exponential function but different from substance I, starts to be added at regular intervals. 3. The relative levels of the two substances can be added up. 4. The optimal dose-scheme for the most regular effect is to be sought. According to the relations derived in repost (5) published previously a slide ruler and a nomogram are constructed by the authors for that purpose. The scales are described as well as how to work with them. Some examples are included. The slide ruler and the nomogram are suitable for some further calcaulations in cumulation kinetics, which is briefly mentioned. These expedients are mainly meant for the application of cardiac glycosides. The same principle can be used in all cases to which the assumptions mentioned above apply.", "contents": "[A slide ruler and nomogram for calculations in cumulation kinetics of cardiac glycosides (author's transl)]. 1. Substance I, whose elimination we can approximate with an exponential function, is active in the organism. 2. At a given moment substance II with the same onset of action whose elimination we also can approximate with an exponential function but different from substance I, starts to be added at regular intervals. 3. The relative levels of the two substances can be added up. 4. The optimal dose-scheme for the most regular effect is to be sought. According to the relations derived in repost (5) published previously a slide ruler and a nomogram are constructed by the authors for that purpose. The scales are described as well as how to work with them. Some examples are included. The slide ruler and the nomogram are suitable for some further calcaulations in cumulation kinetics, which is briefly mentioned. These expedients are mainly meant for the application of cardiac glycosides. The same principle can be used in all cases to which the assumptions mentioned above apply."} {"id": "PMID:1267747", "title": "Human Herpes simplex encephalitis (cellular events).", "content": "Electron microscopic demonstration of herpes viral particles in cerebral tissues obtained at autopsy was easily accomplished. Analysis of the structural abnormalities in this case offers support for the proposed mechanisms of cellular injury in herpes simplex encephalitis. Interference with synthesis of nucleic acids and glycoproteins which has been suggested by in vitro studies correlates well with the structural abnormalities of endoplasmic reticulum cisternae and changes in nuclear membranes, described in the case reported herein.", "contents": "Human Herpes simplex encephalitis (cellular events). Electron microscopic demonstration of herpes viral particles in cerebral tissues obtained at autopsy was easily accomplished. Analysis of the structural abnormalities in this case offers support for the proposed mechanisms of cellular injury in herpes simplex encephalitis. Interference with synthesis of nucleic acids and glycoproteins which has been suggested by in vitro studies correlates well with the structural abnormalities of endoplasmic reticulum cisternae and changes in nuclear membranes, described in the case reported herein."} {"id": "PMID:1267743", "title": "The determination of the myocardial extracellular space in the cat in vivo: a comparative methodological study.", "content": "The myocardial extracellular space (ECS) was determined in cats in vivo by means of the ECS indicators, inulin and sulfanilic acid and, additionally, as glucose space. Experiments were carried out in cats subjected to bilateral kidney ligation (single injection) and in intact cats (single injection or infusion of indicator). The heart was clamped by instant deep-freezing in situ; this technique was compared, in renally-ligated cats, with excision and subsequent freezing of the heart in liquid nitrogen. The myocardial blood content was significantly decreased, and the myocardial lactate concentration significantly increased in excised, as compared with in situ-clamped hearts. Renally-ligated cats showed marked hypotension. The mean myocardial blood content was also significantly lower than in intact animals. A highly significant correlation was found between myocardial blood content and blood pressure for all experiments with instant deep-freezing. The mean inulin ECS value in renally-ligated cats was 22.7 +/- 1.5 ml. In accordance with the fact that the ECS is dependent on the tissure blood content, the corresponding values in intact animals were significantly higher, 25.9 +/- 2.5 ml (single injection) and 26.3 +/- 3.9 ml (infusion), calculated per 100 g tissue wet weight. Similar values were obtained for the glucose and sulfanilic acid ECS. If the interstitial space, an expression independent of the tissue blood content is used as space parameter, no significant differences were found under any of the present experimental conditions.", "contents": "The determination of the myocardial extracellular space in the cat in vivo: a comparative methodological study. The myocardial extracellular space (ECS) was determined in cats in vivo by means of the ECS indicators, inulin and sulfanilic acid and, additionally, as glucose space. Experiments were carried out in cats subjected to bilateral kidney ligation (single injection) and in intact cats (single injection or infusion of indicator). The heart was clamped by instant deep-freezing in situ; this technique was compared, in renally-ligated cats, with excision and subsequent freezing of the heart in liquid nitrogen. The myocardial blood content was significantly decreased, and the myocardial lactate concentration significantly increased in excised, as compared with in situ-clamped hearts. Renally-ligated cats showed marked hypotension. The mean myocardial blood content was also significantly lower than in intact animals. A highly significant correlation was found between myocardial blood content and blood pressure for all experiments with instant deep-freezing. The mean inulin ECS value in renally-ligated cats was 22.7 +/- 1.5 ml. In accordance with the fact that the ECS is dependent on the tissure blood content, the corresponding values in intact animals were significantly higher, 25.9 +/- 2.5 ml (single injection) and 26.3 +/- 3.9 ml (infusion), calculated per 100 g tissue wet weight. Similar values were obtained for the glucose and sulfanilic acid ECS. If the interstitial space, an expression independent of the tissue blood content is used as space parameter, no significant differences were found under any of the present experimental conditions."} {"id": "PMID:1267744", "title": "Cardiovascular effects of high doses of thiamine (vit B1) in the dog with special reference to myocardial oxygen consumption.", "content": "The purpose of this study was to determine the reactions of the cardiovascular system with special reference to myocardial oxygen consumption (MVO2) after the administration of graded doses (up to 2.4 g/kg) of thiamine. The data obtained indicate that thiamine: 1. Decreases mean peripheral pressure up to 25%. 2. Decreases LVEDP, left ventricular pressure, and LV dP/dtmax up to 10%, 15%, and 20% respectively. 3. Reduces pulse rate up to 25%. 4. Reduces coronary sinus blood flow up to 31%. 5. Reduces myocardial oxygen consumption up to 45%. The reduction in LVEDP, LVP, and LV dP/dtmax could be antagonized by dextran or norepinephrine infusion. It is suggested that thiamine blocks alpha-receptors which leads to pooling of blood with a concomitant reduction in pre- and afterload of the heart. The effect on MVO2 suggests that thiamine, the essential coenzyme for the formation of high energy substrates reduced the metabolic needs of the heart. The drug warrants further investigation for the treatment of myocardial ischemia.", "contents": "Cardiovascular effects of high doses of thiamine (vit B1) in the dog with special reference to myocardial oxygen consumption. The purpose of this study was to determine the reactions of the cardiovascular system with special reference to myocardial oxygen consumption (MVO2) after the administration of graded doses (up to 2.4 g/kg) of thiamine. The data obtained indicate that thiamine: 1. Decreases mean peripheral pressure up to 25%. 2. Decreases LVEDP, left ventricular pressure, and LV dP/dtmax up to 10%, 15%, and 20% respectively. 3. Reduces pulse rate up to 25%. 4. Reduces coronary sinus blood flow up to 31%. 5. Reduces myocardial oxygen consumption up to 45%. The reduction in LVEDP, LVP, and LV dP/dtmax could be antagonized by dextran or norepinephrine infusion. It is suggested that thiamine blocks alpha-receptors which leads to pooling of blood with a concomitant reduction in pre- and afterload of the heart. The effect on MVO2 suggests that thiamine, the essential coenzyme for the formation of high energy substrates reduced the metabolic needs of the heart. The drug warrants further investigation for the treatment of myocardial ischemia."} {"id": "PMID:1267749", "title": "Structural analysis of pulmonary vascular changes in a case of infantile calcifying arteriopathy.", "content": "In a well documented case of ACI, the pulmonary vessels were subjected to light microscopy, radiography, electron microscopy and X-ray microanalysis. The analysis of calcified foci in the walls of large and medium pulmonary arteries demonstrated a marked correlation between the deposits of calcium and phosphorus and the number of elastic fibers. The interpretation of our observations is in favour of a congenital defect of elastic fiber formation in the vascular walls, followed by calcification. Massive accumulation of calcium in the vascular walls was associated with tissue destruction, fragmentation of fibers and formation of irregular calcified foci which provoked a foreign-body reaction.", "contents": "Structural analysis of pulmonary vascular changes in a case of infantile calcifying arteriopathy. In a well documented case of ACI, the pulmonary vessels were subjected to light microscopy, radiography, electron microscopy and X-ray microanalysis. The analysis of calcified foci in the walls of large and medium pulmonary arteries demonstrated a marked correlation between the deposits of calcium and phosphorus and the number of elastic fibers. The interpretation of our observations is in favour of a congenital defect of elastic fiber formation in the vascular walls, followed by calcification. Massive accumulation of calcium in the vascular walls was associated with tissue destruction, fragmentation of fibers and formation of irregular calcified foci which provoked a foreign-body reaction."} {"id": "PMID:1267748", "title": "Effect of cerium on the rat liver: an ultrastructural and biochemical study.", "content": "In rats, liver steatosis and necrosis were induced by cerous chloride (CeCl3) and the evolution of these changes was examined. By electron microscopy, 17 hours after CeCl3 treatment, dilation, disorganization and degranulation of the rough endoplasmic reticulum (RER) were noted with an increase in the number and electron density of lysosome-like bodies. In addition, nuclear chromatin showed showed a marked focal electron density, and the nuclear membrane appeared to be interrupted. At 24 hours, the RER was markedly dilated and degranulated, with free ribosomes aggregated in the cytoplasm. The Golgi cisternae appeared to be empty. There was an increase in the number and size of lipid droplets, with depletion of glycogen. At 48 hours, a massive proliferation of smooth endoplasmic reticulum (SER) vesicles occurred. Large lipid droplets were scattered throughout the cytoplasm, while the mitochondria displayed mild changes. By the 8th day, the number of lipid droplets returned to normal; no abnormalities were detected in the other cell organelles. Biochemically, the total hepatic ATP levels fell significantly by the 12th hour, dropping to a minimum by the 48th hour. The liver was gradually depleted of glycogen within the first 48 hours, while hepatic triglycerides increased rapidly, reaching a peak at 96 hours. Exogenous administration of adenine, ATP (adenosine triphosphate), or tryptophan completely prevented CeCl3-induced mortality; hepatic fat accumulation and necrosis were markedly decreased. Glucose, dl-methionine, and choline had no protective effect. It appears that a defect in hepatocellular lipoprotein synthesis and/or release may be responsible for lipid accumulation.", "contents": "Effect of cerium on the rat liver: an ultrastructural and biochemical study. In rats, liver steatosis and necrosis were induced by cerous chloride (CeCl3) and the evolution of these changes was examined. By electron microscopy, 17 hours after CeCl3 treatment, dilation, disorganization and degranulation of the rough endoplasmic reticulum (RER) were noted with an increase in the number and electron density of lysosome-like bodies. In addition, nuclear chromatin showed showed a marked focal electron density, and the nuclear membrane appeared to be interrupted. At 24 hours, the RER was markedly dilated and degranulated, with free ribosomes aggregated in the cytoplasm. The Golgi cisternae appeared to be empty. There was an increase in the number and size of lipid droplets, with depletion of glycogen. At 48 hours, a massive proliferation of smooth endoplasmic reticulum (SER) vesicles occurred. Large lipid droplets were scattered throughout the cytoplasm, while the mitochondria displayed mild changes. By the 8th day, the number of lipid droplets returned to normal; no abnormalities were detected in the other cell organelles. Biochemically, the total hepatic ATP levels fell significantly by the 12th hour, dropping to a minimum by the 48th hour. The liver was gradually depleted of glycogen within the first 48 hours, while hepatic triglycerides increased rapidly, reaching a peak at 96 hours. Exogenous administration of adenine, ATP (adenosine triphosphate), or tryptophan completely prevented CeCl3-induced mortality; hepatic fat accumulation and necrosis were markedly decreased. Glucose, dl-methionine, and choline had no protective effect. It appears that a defect in hepatocellular lipoprotein synthesis and/or release may be responsible for lipid accumulation."} {"id": "PMID:1267745", "title": "[Functional anatomy of the venous inflow in the human fetal heart (author's transl)].", "content": "Heart and cardiac veins of human fetuses (85-190 mm C.R. length) were dissected in situ by dorsal or ventral access. The atrial wall was partially removed. Muscle tissue and blood vessels were studied histologically. The pattern of the blood vessels (except the pulmonary veins) and their opening into the heart is presented synoptically. The following terms are discussed: posterior caval channel, sinus venarum, torus Loweri, atrial septa, and foramen ovale, respectively. Also discussed is the architecture of the muscles of the right atrium in systole and diastole. A correlation has been made with corresponding physiological data.", "contents": "[Functional anatomy of the venous inflow in the human fetal heart (author's transl)]. Heart and cardiac veins of human fetuses (85-190 mm C.R. length) were dissected in situ by dorsal or ventral access. The atrial wall was partially removed. Muscle tissue and blood vessels were studied histologically. The pattern of the blood vessels (except the pulmonary veins) and their opening into the heart is presented synoptically. The following terms are discussed: posterior caval channel, sinus venarum, torus Loweri, atrial septa, and foramen ovale, respectively. Also discussed is the architecture of the muscles of the right atrium in systole and diastole. A correlation has been made with corresponding physiological data."} {"id": "PMID:1267746", "title": "[Congenitally corrected transposition of the great vessels throughout ventricular inversion (author's transl)].", "content": "Congenitally corrected transposition of the great vessels is a cardiac anomaly in which the pulmonary artery and the aorta are transposed in relation to one another but in which the flow of blood is maintained in the physiologic direction. In this condition there is a concomitant inversion of the ventricular chambers. 8 patients--5 adults and 3 children--with this condition have been reviewed with special attention to clinical symptoms and electrocardiographic and roent-genologic features. The anomaly is of importance because it is much more common than formerly believed. Frequently associated cardiac defects are correctable by surgical procedures. Therefore a preoperatively firmly established disgnosis is necessary by angiocardiography and heart catheterization.", "contents": "[Congenitally corrected transposition of the great vessels throughout ventricular inversion (author's transl)]. Congenitally corrected transposition of the great vessels is a cardiac anomaly in which the pulmonary artery and the aorta are transposed in relation to one another but in which the flow of blood is maintained in the physiologic direction. In this condition there is a concomitant inversion of the ventricular chambers. 8 patients--5 adults and 3 children--with this condition have been reviewed with special attention to clinical symptoms and electrocardiographic and roent-genologic features. The anomaly is of importance because it is much more common than formerly believed. Frequently associated cardiac defects are correctable by surgical procedures. Therefore a preoperatively firmly established disgnosis is necessary by angiocardiography and heart catheterization."} {"id": "PMID:1267859", "title": "Adrenocortical suppression and myocardial infarction in non-arteriosclerotic (virgin) and arteriosclerotic (breeder) rats.", "content": "Non-arteriosclerotic, virgin and arteriosclerotic, breeder rats were treated with aniline to suppress adrenal steroidogenic capacity and responsiveness to the stress of acute myocardial infarction. After two weeks of aniline treatment, some of the non-arteriosclerotic and arteriosclerotic animals were given two injections of isoproterenol, spaced 24 h apart, to induce massive myocardial infraction. On the 3 rd day, when myocardial necrosis reaches its zenith, the animals were sacrificed. Aniline-induced adrenal insufficiency caused increased mortality, absence of congestive heart failure, cardiac and adrenal enlargement but no evidence of the characteristic intense catabolism and increased corticoid production which attends acute myocardial infarction. Serum enzymes, e.g., SGOT, SGPT and LDH, triglycerides, but not glucose, free fatty acids and cholesterol, became acutely elevated in animals treated with aniline and isoproterenol. Animals developed a fatty liver, beta cell degranulation, post hypophy-sectomy-like changes in their adrenal cortices, unusually severe infarction, marked distention of intermuscular spaces, frequent foci of dystrophic calcification and cartilaginous metaplasia of the papillary muscles. It is believed that aniline-induced adrenal suppression altered the usual pathophysiologic response to acute myocardial infarction.", "contents": "Adrenocortical suppression and myocardial infarction in non-arteriosclerotic (virgin) and arteriosclerotic (breeder) rats. Non-arteriosclerotic, virgin and arteriosclerotic, breeder rats were treated with aniline to suppress adrenal steroidogenic capacity and responsiveness to the stress of acute myocardial infarction. After two weeks of aniline treatment, some of the non-arteriosclerotic and arteriosclerotic animals were given two injections of isoproterenol, spaced 24 h apart, to induce massive myocardial infraction. On the 3 rd day, when myocardial necrosis reaches its zenith, the animals were sacrificed. Aniline-induced adrenal insufficiency caused increased mortality, absence of congestive heart failure, cardiac and adrenal enlargement but no evidence of the characteristic intense catabolism and increased corticoid production which attends acute myocardial infarction. Serum enzymes, e.g., SGOT, SGPT and LDH, triglycerides, but not glucose, free fatty acids and cholesterol, became acutely elevated in animals treated with aniline and isoproterenol. Animals developed a fatty liver, beta cell degranulation, post hypophy-sectomy-like changes in their adrenal cortices, unusually severe infarction, marked distention of intermuscular spaces, frequent foci of dystrophic calcification and cartilaginous metaplasia of the papillary muscles. It is believed that aniline-induced adrenal suppression altered the usual pathophysiologic response to acute myocardial infarction."} {"id": "PMID:1267860", "title": "Hemodynamically-induced increase in soluble collagen in the anastomosed veins of experimental arteriovenous fistulae.", "content": "External jugular veins that had been subjected to the hemodynamic stresses produced by experimental arteriovenous anastomosis developed 2% increased total protein contents and 17% increased collagen contents. When the stressed veins were homogenized and extracted with saline solutions, statistically significant increases in the saline-soluble proteins and in the saline-soluble collagen (87% and 267%, respectively) were observed. Increased amounts of low molecular weight peptides were found in the extracts. A fraction of these peptides could be degraded by Clostridium collagenase. The saline extract also contained proteins which resembled by their amino-acid composition the acidic structural proteins of the connective tissues. Additonally, in 3 dogs so tested, changes were found in the hydroxylation and glycosylation of lysine from gelatin extracts as well as in the lysine and desmosine contents of the insoluble elastin fractions. This is the first demonstration of a hemodynamically induced increase in the saline solubility of connective tissue proteins in the absence of dietary manipulations.", "contents": "Hemodynamically-induced increase in soluble collagen in the anastomosed veins of experimental arteriovenous fistulae. External jugular veins that had been subjected to the hemodynamic stresses produced by experimental arteriovenous anastomosis developed 2% increased total protein contents and 17% increased collagen contents. When the stressed veins were homogenized and extracted with saline solutions, statistically significant increases in the saline-soluble proteins and in the saline-soluble collagen (87% and 267%, respectively) were observed. Increased amounts of low molecular weight peptides were found in the extracts. A fraction of these peptides could be degraded by Clostridium collagenase. The saline extract also contained proteins which resembled by their amino-acid composition the acidic structural proteins of the connective tissues. Additonally, in 3 dogs so tested, changes were found in the hydroxylation and glycosylation of lysine from gelatin extracts as well as in the lysine and desmosine contents of the insoluble elastin fractions. This is the first demonstration of a hemodynamically induced increase in the saline solubility of connective tissue proteins in the absence of dietary manipulations."} {"id": "PMID:1267861", "title": "Chronic smoking in an animal model. Effects on clotting and fibrinolysis.", "content": "The effects of chronic smoking upon fibrinogen turnover and other clotting parameters, were studied prospectively in an animal model maintained on a chronic program for a period of 18 months. The animal received the equivalent on a weight basis of 11/2 packs of cigarettes daily, smoked by a human subject with the weight of 70 kg. The obtained results suggested significant enhancement of the coagulation mechanism in the smoking animals developing over the period of observation particularly when combined with high lipid diet.", "contents": "Chronic smoking in an animal model. Effects on clotting and fibrinolysis. The effects of chronic smoking upon fibrinogen turnover and other clotting parameters, were studied prospectively in an animal model maintained on a chronic program for a period of 18 months. The animal received the equivalent on a weight basis of 11/2 packs of cigarettes daily, smoked by a human subject with the weight of 70 kg. The obtained results suggested significant enhancement of the coagulation mechanism in the smoking animals developing over the period of observation particularly when combined with high lipid diet."} {"id": "PMID:1267862", "title": "Studies on the distribution of lipids within fibrous plaques.", "content": "The present report is an attempt to determine the nature of the circulation of lipids within fibrous plaques by studying the pattern of lipid distribution within the plaques. The material was obtained from aortas from 405 mammals and birds dying in the Oklahoma City Zoo. Analysis of the pattern of lipid distribution in 187 lipid containing aortic fibrous plaques suggested that most of the lipids entered the plaques at the shoulders and circulated from there toward the centers, usually in the outermost layers of the plaques.", "contents": "Studies on the distribution of lipids within fibrous plaques. The present report is an attempt to determine the nature of the circulation of lipids within fibrous plaques by studying the pattern of lipid distribution within the plaques. The material was obtained from aortas from 405 mammals and birds dying in the Oklahoma City Zoo. Analysis of the pattern of lipid distribution in 187 lipid containing aortic fibrous plaques suggested that most of the lipids entered the plaques at the shoulders and circulated from there toward the centers, usually in the outermost layers of the plaques."} {"id": "PMID:1267864", "title": "Individual cigarette usage: self-reported data as a function of respondent-reported data.", "content": "The interview method was used to collect data from living respondent-subject pairs regarding cigarette usage of the subject; the nonsmoker subject was explicitly not studied. Several different measures of usage were tested. The mean correlation coefficient between subject-reported data and the corresponding respondent-reported data was 0.86; that is, at least 70% of the variability in subject-reported data can be accounted for from information obtained from an appropriate living respondent closely associated with the subject. Selected regression equations are presented for estimating cigarette usage of a subject from data provided by a respondent.", "contents": "Individual cigarette usage: self-reported data as a function of respondent-reported data. The interview method was used to collect data from living respondent-subject pairs regarding cigarette usage of the subject; the nonsmoker subject was explicitly not studied. Several different measures of usage were tested. The mean correlation coefficient between subject-reported data and the corresponding respondent-reported data was 0.86; that is, at least 70% of the variability in subject-reported data can be accounted for from information obtained from an appropriate living respondent closely associated with the subject. Selected regression equations are presented for estimating cigarette usage of a subject from data provided by a respondent."} {"id": "PMID:1267863", "title": "Cigarette smoking and atherosclerosis in autopsied men.", "content": "The association of cigarette smoking and atherosclerorosis was investigated in 1320 autopsied men, 25--64 years of age. Aortic and coronary lesions were evaluated visually in coded specimens and objectively by analysis of radiographs. Using schedules that had been tested on pairs of living persons, interviewers obtained estimates of cigarette smoking habits of the deceased men from surviving relatives. Data were analysed for black and white men in the total sample of cases and also in groups according to the presence (selected disease group) or absence (basal group) of diseases thought to be associated with smoking (emphysema, lung cancer, etc.) or with coronary heart disease (myocardial infarction, hypertension, diabetes, stroke, etc.). Atherosclerotic involvement of aorta and coronary arteries was greatest in heavy smokers and least in nonsmokers for both races in the total sample of cases, the basal group and the selected disease group.", "contents": "Cigarette smoking and atherosclerosis in autopsied men. The association of cigarette smoking and atherosclerorosis was investigated in 1320 autopsied men, 25--64 years of age. Aortic and coronary lesions were evaluated visually in coded specimens and objectively by analysis of radiographs. Using schedules that had been tested on pairs of living persons, interviewers obtained estimates of cigarette smoking habits of the deceased men from surviving relatives. Data were analysed for black and white men in the total sample of cases and also in groups according to the presence (selected disease group) or absence (basal group) of diseases thought to be associated with smoking (emphysema, lung cancer, etc.) or with coronary heart disease (myocardial infarction, hypertension, diabetes, stroke, etc.). Atherosclerotic involvement of aorta and coronary arteries was greatest in heavy smokers and least in nonsmokers for both races in the total sample of cases, the basal group and the selected disease group."} {"id": "PMID:1267865", "title": "A nicotinic acid ester and experimental atherosclerosis: no significant effect of treatment with niceritrol (pentaerythritoltetranicotinate) on cholesterol in aorta of rabbits previously fed with cholesterol-enriched diet.", "content": "The influence of niceritrol on cholesterol in serum, liver and inner aorta of 115 rabbits was studied during a period where a cholesterol-enriched diet was given and during two succeeding periods after which cholesterol addition to the diet was discontinued. Niceritrol given together with cholesterol for 6 weeks reduced significantly the concentration of cholesterol in serum and liver, but not in the inner aorta. During 16 weeks decrease of serum cholesterol after discontinuation of cholesterol feeding no significant effect of niceritrol was observed on the decrease in serum and liver cholesterol or on the concentration of cholesterol in inner aorta. When serum cholesterol had normalized 16 weeks after discontinuation of cholesterol feeding, addition of niceritrol to the diet for the following 16 weeks did not significantly affect the concentration of cholesterol in liver and inner aorta. Animals in all groups were injected intravenously with an equal amount of [3H] cholesterol 3 weeks before discontinuing cholesterol feeding. Niceritrol did not significantly affect the amount of accumulated labelled cholesterol in inner aorta. The present results indicated that niceritrol had no significant effects on metabolism of cholesterol in inner aorta of the hypercholesterolemic and previously hypercholesterolemic rabbits.", "contents": "A nicotinic acid ester and experimental atherosclerosis: no significant effect of treatment with niceritrol (pentaerythritoltetranicotinate) on cholesterol in aorta of rabbits previously fed with cholesterol-enriched diet. The influence of niceritrol on cholesterol in serum, liver and inner aorta of 115 rabbits was studied during a period where a cholesterol-enriched diet was given and during two succeeding periods after which cholesterol addition to the diet was discontinued. Niceritrol given together with cholesterol for 6 weeks reduced significantly the concentration of cholesterol in serum and liver, but not in the inner aorta. During 16 weeks decrease of serum cholesterol after discontinuation of cholesterol feeding no significant effect of niceritrol was observed on the decrease in serum and liver cholesterol or on the concentration of cholesterol in inner aorta. When serum cholesterol had normalized 16 weeks after discontinuation of cholesterol feeding, addition of niceritrol to the diet for the following 16 weeks did not significantly affect the concentration of cholesterol in liver and inner aorta. Animals in all groups were injected intravenously with an equal amount of [3H] cholesterol 3 weeks before discontinuing cholesterol feeding. Niceritrol did not significantly affect the amount of accumulated labelled cholesterol in inner aorta. The present results indicated that niceritrol had no significant effects on metabolism of cholesterol in inner aorta of the hypercholesterolemic and previously hypercholesterolemic rabbits."} {"id": "PMID:1267867", "title": "A classification of fistula-in-ano.", "content": "A classification of anal fistulas is presented, which is the result of an analysis of 400 cases treated over the past 15 years, based on the pathogenesis of the disease and the normal muscular anatomy of the pelvic floor. Four main types were found but numerous variations of each occur, which are described. It is hoped that this will alert the surgeon to the various complex situations that he may encounter.", "contents": "A classification of fistula-in-ano. A classification of anal fistulas is presented, which is the result of an analysis of 400 cases treated over the past 15 years, based on the pathogenesis of the disease and the normal muscular anatomy of the pelvic floor. Four main types were found but numerous variations of each occur, which are described. It is hoped that this will alert the surgeon to the various complex situations that he may encounter."} {"id": "PMID:1267868", "title": "Family studies in cancer of the colon and rectum.", "content": "Family histories were obtained from 209 patients undergoing treatment for cancer of the colon or rectum at St Mark's Hospital. Death certificates were obtained for parents and siblings who had died. Among these, the number of deaths from cancer of the bowel was more than three times that expected for a comparable group from the general population. There are three principal features which, if present in an index case, are associated with the likelihood that other members of the family will also have had cancer of the large bowel. These are, first, the presence of multiple benign or malignant tumours in the large bowel, secondly, a history of previous primary carcinoma or adenoma of the large bowel and, thirdly, early age of onset of carcinoma of the bowel.", "contents": "Family studies in cancer of the colon and rectum. Family histories were obtained from 209 patients undergoing treatment for cancer of the colon or rectum at St Mark's Hospital. Death certificates were obtained for parents and siblings who had died. Among these, the number of deaths from cancer of the bowel was more than three times that expected for a comparable group from the general population. There are three principal features which, if present in an index case, are associated with the likelihood that other members of the family will also have had cancer of the large bowel. These are, first, the presence of multiple benign or malignant tumours in the large bowel, secondly, a history of previous primary carcinoma or adenoma of the large bowel and, thirdly, early age of onset of carcinoma of the bowel."} {"id": "PMID:1267869", "title": "Familial cancer of the gastro-intestinal tract.", "content": "A family with a high incidence of early onset gastrointestinal carcinoma is described. Individuals from four generations have been proved to have had the disease. The management of individuals as yet unaffected is discussed and a regime for follow-up suggested.", "contents": "Familial cancer of the gastro-intestinal tract. A family with a high incidence of early onset gastrointestinal carcinoma is described. Individuals from four generations have been proved to have had the disease. The management of individuals as yet unaffected is discussed and a regime for follow-up suggested."} {"id": "PMID:1267866", "title": "Tetronic 701-a novel hypocholesterolaemic agent.", "content": "The Tetronic series of polymeric surface-active agents were screened for hypocholesterolaemic activity in rats fed on a semi-synthetic hypercholesterolaemic diet. Only Tetronics 701 and 702 were active and the former was further investigated. Tetronic 701 lowered serum and liver cholesterol in rats fed on a semi-synthetic diet, with or without cholesterol, but not in rats fed on stock laboratory diet. A dose-related growth depression was observed. The compound was hypocholesterolaemic in chicks and rabbits fed on cholesterol-containing diets. The uptake of a single dose of cholesterol into liver and serum was inhibited in rats given Tetronic 701. Tetronics 701 and 702 were effective in precipitating cholesterol from mixed micelles in vitro. Non-hypocholesterolaemic Tetronics were inactive in this respect. A series of tetraesters of tetronic 701 were prepared and tested in rats fed on a semi-synthetic hypercholesterolaemic diet. Several were hypocholesterolaemic and the tetrabenzoate was of especial interest in that it depressed growth less than did Tetronic 701 itself.", "contents": "Tetronic 701-a novel hypocholesterolaemic agent. The Tetronic series of polymeric surface-active agents were screened for hypocholesterolaemic activity in rats fed on a semi-synthetic hypercholesterolaemic diet. Only Tetronics 701 and 702 were active and the former was further investigated. Tetronic 701 lowered serum and liver cholesterol in rats fed on a semi-synthetic diet, with or without cholesterol, but not in rats fed on stock laboratory diet. A dose-related growth depression was observed. The compound was hypocholesterolaemic in chicks and rabbits fed on cholesterol-containing diets. The uptake of a single dose of cholesterol into liver and serum was inhibited in rats given Tetronic 701. Tetronics 701 and 702 were effective in precipitating cholesterol from mixed micelles in vitro. Non-hypocholesterolaemic Tetronics were inactive in this respect. A series of tetraesters of tetronic 701 were prepared and tested in rats fed on a semi-synthetic hypercholesterolaemic diet. Several were hypocholesterolaemic and the tetrabenzoate was of especial interest in that it depressed growth less than did Tetronic 701 itself."} {"id": "PMID:1267870", "title": "Severe pseudomembranous colitis after lincomycin and clindamycin.", "content": "Four cases of severe pseudomembranous colitis following the use of lincomycin and clindamycin are described; 2 required emergency total colectomy and 2 died. Cases of such gravity after the use of these drugs have not been previously reported. On hundred and fifty-six orthopaedic cases where clindamycin and lincomycin were used postoperatively are reviewed; 34 had diarrhoea (22 per cent), and 3 of the severe cases occurred in this group. The diagnosis of pseudomembranous colitis may be difficult as the latent period from initiation of drug therapy to commencement of diarrhoea may be as much as 18 days, and that from cessation of drug therapy may be as much as 11 days. The value of early sigmoidoscopy in cases of diarrhoea of obscure aetiology is emphasized, and the characteristic sigmoidoscopic and histological appearances of pseudomembranous colitis are described. As these drugs may produce a lethal condition it is suggested that they should be used with appropriate discretion, especially in the elderly female who appears to be most at risk.", "contents": "Severe pseudomembranous colitis after lincomycin and clindamycin. Four cases of severe pseudomembranous colitis following the use of lincomycin and clindamycin are described; 2 required emergency total colectomy and 2 died. Cases of such gravity after the use of these drugs have not been previously reported. On hundred and fifty-six orthopaedic cases where clindamycin and lincomycin were used postoperatively are reviewed; 34 had diarrhoea (22 per cent), and 3 of the severe cases occurred in this group. The diagnosis of pseudomembranous colitis may be difficult as the latent period from initiation of drug therapy to commencement of diarrhoea may be as much as 18 days, and that from cessation of drug therapy may be as much as 11 days. The value of early sigmoidoscopy in cases of diarrhoea of obscure aetiology is emphasized, and the characteristic sigmoidoscopic and histological appearances of pseudomembranous colitis are described. As these drugs may produce a lethal condition it is suggested that they should be used with appropriate discretion, especially in the elderly female who appears to be most at risk."} {"id": "PMID:1267871", "title": "Symptomatic hypoglycaemia, liver glycogen depletion and cirrhosis following jejuno-ileal bypass for gross obesity.", "content": "A new complication following jejuno-ileal bypass for gross obesity is described. The patient suffered from hypoglycaemic attacks which were associated with total depletion of liver glycogen together with a progressive micronodular cirrhosis. Increased dietary protein and calorie content relieved her symptoms, restored liver glycogen but had no effect on the development of the cirrhosis over the next 12 months.", "contents": "Symptomatic hypoglycaemia, liver glycogen depletion and cirrhosis following jejuno-ileal bypass for gross obesity. A new complication following jejuno-ileal bypass for gross obesity is described. The patient suffered from hypoglycaemic attacks which were associated with total depletion of liver glycogen together with a progressive micronodular cirrhosis. Increased dietary protein and calorie content relieved her symptoms, restored liver glycogen but had no effect on the development of the cirrhosis over the next 12 months."} {"id": "PMID:1267872", "title": "Chronic intussusception in children.", "content": "Three children with chronic intussusception are reported together with a review of the literature. Neither the palpation of a mass nor the passage of blood per rectum was necessary for the diagnosis. Weight loss was seen in each case and 1 child was investigated for malabsorption. In all 3 children there was a delay in diagnosis, and it is suggested that a chronic intussusception should be considered more frequently in children with persistent abdominal symptoms for which no cause can be found. Although a barium enema was helpful diagnostically, it did not result in the reduction of the intussusception. The problem of a recurrence after a reduction and its subsequent management is discussed.", "contents": "Chronic intussusception in children. Three children with chronic intussusception are reported together with a review of the literature. Neither the palpation of a mass nor the passage of blood per rectum was necessary for the diagnosis. Weight loss was seen in each case and 1 child was investigated for malabsorption. In all 3 children there was a delay in diagnosis, and it is suggested that a chronic intussusception should be considered more frequently in children with persistent abdominal symptoms for which no cause can be found. Although a barium enema was helpful diagnostically, it did not result in the reduction of the intussusception. The problem of a recurrence after a reduction and its subsequent management is discussed."} {"id": "PMID:1267873", "title": "Splenectomy in childhood: a review in England and Wales, 1960-4.", "content": "An investigation was carried out of 821 children under the age of 16 years who were subjected to splenectomy in England and Wales during the 5 years 1960-4. A postal follow-up study provided satisfactory information concerning 96 per cent of these. Excluding early postoperative deaths, practically all the cases were followed up for 2 years or more and 70 per cent for more than 5 years. Forty-nine children had died since operation, 32 from underlying disease and 17 from infection. Fifty children (6 per cent of the survivors) had major infections considered to be due to the primary condition aggravated by splenectomy. Seven died, all from the primary disease. Sixteen children (2 per cent) developed septicaemic illnesses and 10 died. In these the effect of splenectomy was considered to be the primary factor. Fourteen of the 16 had been operated on in the first 4 years of life. Practically all the serious infections occurred within 3 years of operation and pneumococcus was the organism most frequently implicated. Ninety per cent of the splenectomies in childhood were performed for accidental injury, congenital haemolytic anaemia or idiopathic thrombocytopenic purpura. Accidental injury to the spleen rarely occurs in very young children, and in the other two conditions splenectomy can usually be safely delayed untile over the age of 3 years. If this is achieved it is estimated that the unavoidable risk of dangerous infection is less than 1 per cent. One in 10 splenectomies will be carried out for severe and potentially fatal illnesses and in this situation the risk from operation is of secondary importance. Many such conditions carry increased susceptibility to infection per se or because corticosteroids or other immune suppressants are used in their management. It is recommended that splenectomy be avoided if at all possible during the early years of life. It is further recommended that prophylactic penicillin be administered for 3 years following operation whatever its indication and whatever the age of the patient. If the underlying condition itself carries risk of infection more active and more prolonged prophylaxis may be indicated.", "contents": "Splenectomy in childhood: a review in England and Wales, 1960-4. An investigation was carried out of 821 children under the age of 16 years who were subjected to splenectomy in England and Wales during the 5 years 1960-4. A postal follow-up study provided satisfactory information concerning 96 per cent of these. Excluding early postoperative deaths, practically all the cases were followed up for 2 years or more and 70 per cent for more than 5 years. Forty-nine children had died since operation, 32 from underlying disease and 17 from infection. Fifty children (6 per cent of the survivors) had major infections considered to be due to the primary condition aggravated by splenectomy. Seven died, all from the primary disease. Sixteen children (2 per cent) developed septicaemic illnesses and 10 died. In these the effect of splenectomy was considered to be the primary factor. Fourteen of the 16 had been operated on in the first 4 years of life. Practically all the serious infections occurred within 3 years of operation and pneumococcus was the organism most frequently implicated. Ninety per cent of the splenectomies in childhood were performed for accidental injury, congenital haemolytic anaemia or idiopathic thrombocytopenic purpura. Accidental injury to the spleen rarely occurs in very young children, and in the other two conditions splenectomy can usually be safely delayed untile over the age of 3 years. If this is achieved it is estimated that the unavoidable risk of dangerous infection is less than 1 per cent. One in 10 splenectomies will be carried out for severe and potentially fatal illnesses and in this situation the risk from operation is of secondary importance. Many such conditions carry increased susceptibility to infection per se or because corticosteroids or other immune suppressants are used in their management. It is recommended that splenectomy be avoided if at all possible during the early years of life. It is further recommended that prophylactic penicillin be administered for 3 years following operation whatever its indication and whatever the age of the patient. If the underlying condition itself carries risk of infection more active and more prolonged prophylaxis may be indicated."} {"id": "PMID:1267874", "title": "Some observations on gallstones and bile composition.", "content": "A series of 31 consecutive patients undergoing surgery for gallstone disease has been studied and the composition of the gallstones and bile from the gallbladder and common duct determined. As a result of the stone analysis by the X-ray powder diffraction method, the patients were classified according to whether their stones consisted of cholesterol, calcium salts or a mixture of the two. The mean composition of the common duct bile for the groups with cholesterol and mixed stones was just outside the micellar region of cholesterol solubility. The gallbladder bile from the cholesterol group of stone-formers was also supersaturated, but the gallblader bile from the group of mixed stone-formers was undersaturated with respect to cholesterol. None of the patients forming gallstones of calcium salts showed any abnormality in the cholesterol content of their bile.", "contents": "Some observations on gallstones and bile composition. A series of 31 consecutive patients undergoing surgery for gallstone disease has been studied and the composition of the gallstones and bile from the gallbladder and common duct determined. As a result of the stone analysis by the X-ray powder diffraction method, the patients were classified according to whether their stones consisted of cholesterol, calcium salts or a mixture of the two. The mean composition of the common duct bile for the groups with cholesterol and mixed stones was just outside the micellar region of cholesterol solubility. The gallbladder bile from the cholesterol group of stone-formers was also supersaturated, but the gallblader bile from the group of mixed stone-formers was undersaturated with respect to cholesterol. None of the patients forming gallstones of calcium salts showed any abnormality in the cholesterol content of their bile."} {"id": "PMID:1267875", "title": "Retained common bile duct calculi.", "content": "A method of elimination of gallstones remaining in the common bile duct after exploration of the duct is described. The retained stone is flushed through the common duct sphincter into the duodenum using rapid infusion of normal saline via a T tube. The method is quick and simple and is recommended as the first step to take in the management of this discomforting group of patients. The method is not without potential morbidity and should only be carried out under carefully controlled conditions.", "contents": "Retained common bile duct calculi. A method of elimination of gallstones remaining in the common bile duct after exploration of the duct is described. The retained stone is flushed through the common duct sphincter into the duodenum using rapid infusion of normal saline via a T tube. The method is quick and simple and is recommended as the first step to take in the management of this discomforting group of patients. The method is not without potential morbidity and should only be carried out under carefully controlled conditions."} {"id": "PMID:1267876", "title": "Operative cholangiography: criteria which make exploration of the common bile duct desirable.", "content": "The purpose of this study was to evaluate the individual criteria and combination of criteria examined by operative cholangiography which make exploration of the common bile duct desirable. The overall accuracy of exploration of the common bile duct (89 per cent) was similar to that of previous series. In the normal group the accuracy of the criteria established by Le Quesne (1960) is confirmed. The most reliable criteria in the abnormal cholangiograms were the presence of single or multiple filling defects in the common bile duct, the absence of free flow of contrast medium into the duodenum and an abnormality of the terminal narrow segment. Measurements to aid assessment of free flow into the duodenum are suggested. In 34 of 40 positive explorations the common bile duct diameter was 14 mm or less; 10 common bile ducts which contained stones were less than 10 mm in diameter. Excess filling of the intrahepatic ducts was often impossible to judge in the abnormal group and was the least valuable criterion. Attention is drawn to the advantage of an immediate radiological report.", "contents": "Operative cholangiography: criteria which make exploration of the common bile duct desirable. The purpose of this study was to evaluate the individual criteria and combination of criteria examined by operative cholangiography which make exploration of the common bile duct desirable. The overall accuracy of exploration of the common bile duct (89 per cent) was similar to that of previous series. In the normal group the accuracy of the criteria established by Le Quesne (1960) is confirmed. The most reliable criteria in the abnormal cholangiograms were the presence of single or multiple filling defects in the common bile duct, the absence of free flow of contrast medium into the duodenum and an abnormality of the terminal narrow segment. Measurements to aid assessment of free flow into the duodenum are suggested. In 34 of 40 positive explorations the common bile duct diameter was 14 mm or less; 10 common bile ducts which contained stones were less than 10 mm in diameter. Excess filling of the intrahepatic ducts was often impossible to judge in the abnormal group and was the least valuable criterion. Attention is drawn to the advantage of an immediate radiological report."} {"id": "PMID:1267877", "title": "Pancreatic pseudocysts.", "content": "Twenty-seven patients with 32 pancreatic pseudocysts have been seen during the past 10 years at St George's Hospital, London. Two of the pseudocysts were found in unusual positions--one in the right inguinal canal and the other one in the porta hepatis. Approximately half of the pseudocysts in this series followed biliary-induced pancreatitis. The various clinical presentations are reported and the surgical treatment is discussed. Internal drainage is the most effective treatment and in the majority of cases transgastric cystogastrostomy via a tube is the procedure of choice. One death occurred, an overall mortality rate of 3-1 per cent.", "contents": "Pancreatic pseudocysts. Twenty-seven patients with 32 pancreatic pseudocysts have been seen during the past 10 years at St George's Hospital, London. Two of the pseudocysts were found in unusual positions--one in the right inguinal canal and the other one in the porta hepatis. Approximately half of the pseudocysts in this series followed biliary-induced pancreatitis. The various clinical presentations are reported and the surgical treatment is discussed. Internal drainage is the most effective treatment and in the majority of cases transgastric cystogastrostomy via a tube is the procedure of choice. One death occurred, an overall mortality rate of 3-1 per cent."} {"id": "PMID:1267878", "title": "Curling's ulcer: a rare condition.", "content": "A case of Curling's ulceration of the duodenum in a child with 50 per cent burns, requiring operative arrest of the bleeding, is reported, and this condition is reviewed. Inquiry among the surgical units treating burns in Great Britian showed that only 18 cases of alimentary bleeding had been seen in the course of treating some 32 500 patients. The incidence in Europe and Australia appears to be of the same order, but there is a much higher incidence in some burns units in North America. Possible reasons for these differences are examined. The occurrence and treatment of Curling's ulcer in childhood are considered.", "contents": "Curling's ulcer: a rare condition. A case of Curling's ulceration of the duodenum in a child with 50 per cent burns, requiring operative arrest of the bleeding, is reported, and this condition is reviewed. Inquiry among the surgical units treating burns in Great Britian showed that only 18 cases of alimentary bleeding had been seen in the course of treating some 32 500 patients. The incidence in Europe and Australia appears to be of the same order, but there is a much higher incidence in some burns units in North America. Possible reasons for these differences are examined. The occurrence and treatment of Curling's ulcer in childhood are considered."} {"id": "PMID:1267879", "title": "Pleural empyema in association with renal sepsis.", "content": "Five cases of pleural empyema in association with perinephric abscess or renal infection are presented. This represents 4 per cent of a series of 122 pleural empyemas, or 30 per cent of empyemas with subdiaphragmatic aetiology. It is suggested that the renal tract should be investigated in all cases of recurrent or non-resolving pleural empyema of uncertain aetiology.", "contents": "Pleural empyema in association with renal sepsis. Five cases of pleural empyema in association with perinephric abscess or renal infection are presented. This represents 4 per cent of a series of 122 pleural empyemas, or 30 per cent of empyemas with subdiaphragmatic aetiology. It is suggested that the renal tract should be investigated in all cases of recurrent or non-resolving pleural empyema of uncertain aetiology."} {"id": "PMID:1267880", "title": "Delayed arterial embolectomy: a plea for a more active surgical approach.", "content": "In a series of 18 patients delayed embolectomy of the limb was performed 8-63 days after embolism had occurred. Three patients died (2 of them after amputation), and 7 limbs were amputated after surgery. In 10 instances blood flow was fully restored by the operation. Analysis of the 18 cases leads to the conclusion that the success of delayed embolectomy where neuromuscular function is intact depends primarily on surgical technique. Direct embolectomy by local or regional exposure of the obstructed arterial level is shown to produce better results than conventional (distant) balloon catheter embolectomy by proximal incision. This is thought to be due to increased mural adherence of the embolus, with secondary thrombus formation after a delay of 8 days or more. A plea is therefore made for a more aggressive surgical attitude to delayed arterial embolization. Provided that preoperative arteriography has localized the obstructive level and that the patient's general condition allows major vascular surgery, direct removal of the embolus and secondary thrombi by open exposure of the obstructed artery is recommended.", "contents": "Delayed arterial embolectomy: a plea for a more active surgical approach. In a series of 18 patients delayed embolectomy of the limb was performed 8-63 days after embolism had occurred. Three patients died (2 of them after amputation), and 7 limbs were amputated after surgery. In 10 instances blood flow was fully restored by the operation. Analysis of the 18 cases leads to the conclusion that the success of delayed embolectomy where neuromuscular function is intact depends primarily on surgical technique. Direct embolectomy by local or regional exposure of the obstructed arterial level is shown to produce better results than conventional (distant) balloon catheter embolectomy by proximal incision. This is thought to be due to increased mural adherence of the embolus, with secondary thrombus formation after a delay of 8 days or more. A plea is therefore made for a more aggressive surgical attitude to delayed arterial embolization. Provided that preoperative arteriography has localized the obstructive level and that the patient's general condition allows major vascular surgery, direct removal of the embolus and secondary thrombi by open exposure of the obstructed artery is recommended."} {"id": "PMID:1267881", "title": "Bypass grafting to the anterior tibial artery.", "content": "Four patients with severe ischaemia of a leg due to atherosclerotic occlusion of the tibial and peroneal arteries had reversed long saphenous vein grafts to the patent lower part of the anterior tibial artery. Two of these grafts continue to function 19 and 24 months after operation respectively. One graft failed on the fifth postoperative day and another occluded 4 months after operation. The literature on femorotibial grafting has been reviewed. The early failure rate of distal grafting is higher than in the case of femoropopliteal bypass, but a number of otherwise doomed limbs can be salvaged. Contrary to widely held views, grafting to the anterior tibial artery appears to give results comparable to those obtained when the lower anastomosis is made to the posterior tibial artery.", "contents": "Bypass grafting to the anterior tibial artery. Four patients with severe ischaemia of a leg due to atherosclerotic occlusion of the tibial and peroneal arteries had reversed long saphenous vein grafts to the patent lower part of the anterior tibial artery. Two of these grafts continue to function 19 and 24 months after operation respectively. One graft failed on the fifth postoperative day and another occluded 4 months after operation. The literature on femorotibial grafting has been reviewed. The early failure rate of distal grafting is higher than in the case of femoropopliteal bypass, but a number of otherwise doomed limbs can be salvaged. Contrary to widely held views, grafting to the anterior tibial artery appears to give results comparable to those obtained when the lower anastomosis is made to the posterior tibial artery."} {"id": "PMID:1267882", "title": "Leiomyosarcoma of the right common iliac artery: a case report.", "content": "A case initially diagnosed at laparotomy as having a phaeochromocytoma was re-explored after negative biochemical tests and found to have a leiomyosarcoma of the right iliac artery.", "contents": "Leiomyosarcoma of the right common iliac artery: a case report. A case initially diagnosed at laparotomy as having a phaeochromocytoma was re-explored after negative biochemical tests and found to have a leiomyosarcoma of the right iliac artery."} {"id": "PMID:1267884", "title": "Elevation of plasma bromide levels in patients following halothane anesthesia: Time correlation with total halothane dosage.", "content": "Plasma bromide concentrations of 25 patients were determined before and after halothane anesthesia. A high correlation (r greater than .70) between exposure to halothane in MAC-hours and plasma bromide levels 24, 48 and 72 hours later was found. Peak bromide levels occurred 48-72 hours after anesthesia in 16 patients (64 per cent), and ranged from 52 mug/ml (0.65 mEq/l) to 180 mug/mo (2.25 mEq/l). Bromide levels remained elevated for prolonged periods (at least 22 days in some patients). Possible sedative or psychoactive effects of increased plasma bromide levels are discussed.", "contents": "Elevation of plasma bromide levels in patients following halothane anesthesia: Time correlation with total halothane dosage. Plasma bromide concentrations of 25 patients were determined before and after halothane anesthesia. A high correlation (r greater than .70) between exposure to halothane in MAC-hours and plasma bromide levels 24, 48 and 72 hours later was found. Peak bromide levels occurred 48-72 hours after anesthesia in 16 patients (64 per cent), and ranged from 52 mug/ml (0.65 mEq/l) to 180 mug/mo (2.25 mEq/l). Bromide levels remained elevated for prolonged periods (at least 22 days in some patients). Possible sedative or psychoactive effects of increased plasma bromide levels are discussed."} {"id": "PMID:1267885", "title": "Hypoxia and halothane metabolism in vivo: release of inorganic fluoride and halothane metabolite binding to cellular constituents.", "content": "Fluoride release and covalent binding of halothane metabolites were studied in rats pretreated with phenobarbital and anesthestized with halothane in the presence of high (40 per cent) and low (7 per cent) oxygen tensions. The purpose of producing hypoxia was to promote the reductive pathways involved in the metabolism of halothane. Halothane anesthesia under hypoxic conditions caused a significant elevation in the plasma fluoride concentration. There was also a greater than three-fold increase in covalent binding of 14C-halothane metabolites to microsomal lipids in hypoxic rats. The lipid/protein binding ratio in control animals averaged 0.76, while hypoxic animals had a binding ratio of 3.24. The findings demonstrate that defluorination of halothane does occur during hypoxic conditions. It is hypothesized that the products produced by this reductive metabolic pathway are also potentially more hepatotoxic than the oxidative metabolites, based upon the increased covalent binding of halothane metabolites under hypoxic conditions.", "contents": "Hypoxia and halothane metabolism in vivo: release of inorganic fluoride and halothane metabolite binding to cellular constituents. Fluoride release and covalent binding of halothane metabolites were studied in rats pretreated with phenobarbital and anesthestized with halothane in the presence of high (40 per cent) and low (7 per cent) oxygen tensions. The purpose of producing hypoxia was to promote the reductive pathways involved in the metabolism of halothane. Halothane anesthesia under hypoxic conditions caused a significant elevation in the plasma fluoride concentration. There was also a greater than three-fold increase in covalent binding of 14C-halothane metabolites to microsomal lipids in hypoxic rats. The lipid/protein binding ratio in control animals averaged 0.76, while hypoxic animals had a binding ratio of 3.24. The findings demonstrate that defluorination of halothane does occur during hypoxic conditions. It is hypothesized that the products produced by this reductive metabolic pathway are also potentially more hepatotoxic than the oxidative metabolites, based upon the increased covalent binding of halothane metabolites under hypoxic conditions."} {"id": "PMID:1267886", "title": "Localization of molecular halothane in phospholipid bilayer model nerve membranes.", "content": "The molecular motion and distribution of the inhalation anesthetic halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) in a phospholipid bilayer model nerve membrane preparation was studied using fluorine nuclear magnetic resonance. Bilayers containing stable free radicals at known depths were studied to measure possible localization of halothane within certain areas of the bilayer. Bilayer suspensions containing manganese ions in the aqueous phase were used to test the partition of halothane between the aqueous and lipid phases. It was found that halothane rapidly achieves complete exchange throughout the bilayer and the surrounding aqueous phase. The results provide experimental evidence against the formation of anesthetic clathrates hypothesized by Pauling and Miller in their theories of anesthesia.", "contents": "Localization of molecular halothane in phospholipid bilayer model nerve membranes. The molecular motion and distribution of the inhalation anesthetic halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) in a phospholipid bilayer model nerve membrane preparation was studied using fluorine nuclear magnetic resonance. Bilayers containing stable free radicals at known depths were studied to measure possible localization of halothane within certain areas of the bilayer. Bilayer suspensions containing manganese ions in the aqueous phase were used to test the partition of halothane between the aqueous and lipid phases. It was found that halothane rapidly achieves complete exchange throughout the bilayer and the surrounding aqueous phase. The results provide experimental evidence against the formation of anesthetic clathrates hypothesized by Pauling and Miller in their theories of anesthesia."} {"id": "PMID:1267887", "title": "Duration of halothane anesthesia and neuromuscular blockade with d-tubocurarine.", "content": "Cumulative d-tubocurarine dose-response curves were determined in 35 unpremedicated adult surgical patients. In five awake patients with and five awake patients without ulnar nerve block the median effective doses of d-tubocurarine necessary for 50 per cent depression of twitch tension (ED50) were 8.3 and 9.1 mg/m2, respectively. The presence of an ulnar nerve block did not significantly alter ED50, which suggests that the central nervous system has little influence on the d-tubocurarine dose-response curve. The ED50's of d-tubocurarine were 4.8, 4.5, 2.5, 3.2, and 3.8 mg/m2 in patients anesthetized with 1.0 to 1.3 per cent alveolar concentrations of halothane for 10, 20, 40, 80, and 160 minutes, respectively. It is concluded that duration of anesthesia has no effect on neuromuscular blockade by d-tubocurarine.", "contents": "Duration of halothane anesthesia and neuromuscular blockade with d-tubocurarine. Cumulative d-tubocurarine dose-response curves were determined in 35 unpremedicated adult surgical patients. In five awake patients with and five awake patients without ulnar nerve block the median effective doses of d-tubocurarine necessary for 50 per cent depression of twitch tension (ED50) were 8.3 and 9.1 mg/m2, respectively. The presence of an ulnar nerve block did not significantly alter ED50, which suggests that the central nervous system has little influence on the d-tubocurarine dose-response curve. The ED50's of d-tubocurarine were 4.8, 4.5, 2.5, 3.2, and 3.8 mg/m2 in patients anesthetized with 1.0 to 1.3 per cent alveolar concentrations of halothane for 10, 20, 40, 80, and 160 minutes, respectively. It is concluded that duration of anesthesia has no effect on neuromuscular blockade by d-tubocurarine."} {"id": "PMID:1267888", "title": "Myocardial depression by nitrous oxide and its reversal by Ca++.", "content": "The effects of 50 per cent nitrous oxide on isometric contractile force of electrically stimulated cat papillary muscle suspended in a Tris-buffered solution at five concentrations of Ca++ ranging from 1 to 15 mM were studied. Compared with an equal concentration of nitrogen, or with pure oxygen, nitrous oxide caused a highly significant reduction in contractile force, averaging 22 per cent at 2.5 mM Ca++. This reduction in force, like that caused by halothane, could be antagonized by increasing [Ca++] in the bathing medium. However, the reductions in force caused by equinarcotic concentrations of halothane and nitrous oxide are significantly different in magnitude, suggesting that the mechanisms of anesthetic action in the central nervous system and in the myocardium may not be the same.", "contents": "Myocardial depression by nitrous oxide and its reversal by Ca++. The effects of 50 per cent nitrous oxide on isometric contractile force of electrically stimulated cat papillary muscle suspended in a Tris-buffered solution at five concentrations of Ca++ ranging from 1 to 15 mM were studied. Compared with an equal concentration of nitrogen, or with pure oxygen, nitrous oxide caused a highly significant reduction in contractile force, averaging 22 per cent at 2.5 mM Ca++. This reduction in force, like that caused by halothane, could be antagonized by increasing [Ca++] in the bathing medium. However, the reductions in force caused by equinarcotic concentrations of halothane and nitrous oxide are significantly different in magnitude, suggesting that the mechanisms of anesthetic action in the central nervous system and in the myocardium may not be the same."} {"id": "PMID:1267890", "title": "The medical malpractice problem, and some possible solutions.", "content": "The solutions to the problems of medical malpractice and malpractice insurance coverage are primarily in the hands of state legislatures. Legislation enacted has been primarily palliative, to assure continued availability of professional liability insurance. Unfortunately, no limit can be placed on the costs of such coverage. Unfortunately, too, no long-term solution has been forthcoming. Any long-term solution must encompass some method or methods of reducing injuries to patients and at the same time changing the system from defense of the physician to compensation of the patient. If such changes are not forthcoming, physicians will become uninsurable and the private practice of medicine as we now know it will disappear in this country.", "contents": "The medical malpractice problem, and some possible solutions. The solutions to the problems of medical malpractice and malpractice insurance coverage are primarily in the hands of state legislatures. Legislation enacted has been primarily palliative, to assure continued availability of professional liability insurance. Unfortunately, no limit can be placed on the costs of such coverage. Unfortunately, too, no long-term solution has been forthcoming. Any long-term solution must encompass some method or methods of reducing injuries to patients and at the same time changing the system from defense of the physician to compensation of the patient. If such changes are not forthcoming, physicians will become uninsurable and the private practice of medicine as we now know it will disappear in this country."} {"id": "PMID:1267905", "title": "Massive left atrial thrombus complicating mitral stenosis with atrial fibrillation: results of surgical treatment.", "content": "Thirty-five patients with massive atrial thrombus complicating mitral stenosis and atrial fibrillation were treated surgically. The mean age in this series is lower than that reported in the West. Furthermore, the incidence of preoperative embolic manifestations has been less frequent in our experience. We believe it is desirable to document the presence of a thrombus by selective left atrial cineangiography. Surgical treatment was accomplished with an acceptable mortality. The vital role played by the use of low-molecular-weight dextran and early anticoagulation in decreasing the incidence of postoperative cerebral embolism is emphasized. Follow-up data in the survivors has shown excellent functional status with no late embolic phenomena in any subject.", "contents": "Massive left atrial thrombus complicating mitral stenosis with atrial fibrillation: results of surgical treatment. Thirty-five patients with massive atrial thrombus complicating mitral stenosis and atrial fibrillation were treated surgically. The mean age in this series is lower than that reported in the West. Furthermore, the incidence of preoperative embolic manifestations has been less frequent in our experience. We believe it is desirable to document the presence of a thrombus by selective left atrial cineangiography. Surgical treatment was accomplished with an acceptable mortality. The vital role played by the use of low-molecular-weight dextran and early anticoagulation in decreasing the incidence of postoperative cerebral embolism is emphasized. Follow-up data in the survivors has shown excellent functional status with no late embolic phenomena in any subject."} {"id": "PMID:1267906", "title": "Surgical treatment of postinfarction ventricular aneurysm.", "content": "We have operated on 62 consecutive patients for postinfarction ventricular aneurysm since coronary bypass grafting became available. Analysis of hemodynamic and angiographic data reveals that the prognosis of operation is favorable if mean pulmonary artery pressure is less than 45 mm Hg and cardiac index is greater than 2.0 L/min/m2; such factors as the preoperative New York Heart Association Functional Class, number of coronary grafts, aneurysm size, left ventricular end-diastolic pressure, and coronary score were not closely related to the outcome of operation. Hospital mortality was 6.5% (4 patients) and late mortality, with a mean follow-up of two years, was 11% (7 patients). The prognosis among survivors was good: 82% (46) achieved NYHA Class I or II status, whereas 87% (54) had been in Class III or IV preoperatively. Concomitant vein grafting with aneurysmectomy did not significantly enhance operative or late survival, nor did it add appreciably to the risk of operation. Long-term benefits of revascularization in addition to aneurysmectomy are expected but not yet proved.", "contents": "Surgical treatment of postinfarction ventricular aneurysm. We have operated on 62 consecutive patients for postinfarction ventricular aneurysm since coronary bypass grafting became available. Analysis of hemodynamic and angiographic data reveals that the prognosis of operation is favorable if mean pulmonary artery pressure is less than 45 mm Hg and cardiac index is greater than 2.0 L/min/m2; such factors as the preoperative New York Heart Association Functional Class, number of coronary grafts, aneurysm size, left ventricular end-diastolic pressure, and coronary score were not closely related to the outcome of operation. Hospital mortality was 6.5% (4 patients) and late mortality, with a mean follow-up of two years, was 11% (7 patients). The prognosis among survivors was good: 82% (46) achieved NYHA Class I or II status, whereas 87% (54) had been in Class III or IV preoperatively. Concomitant vein grafting with aneurysmectomy did not significantly enhance operative or late survival, nor did it add appreciably to the risk of operation. Long-term benefits of revascularization in addition to aneurysmectomy are expected but not yet proved."} {"id": "PMID:1267907", "title": "Communication between the pulmonary and systemic circulations.", "content": "Communications between the pulmonary and systemic circulation occur normally and also in association with a number of pathological entities. On the basis of recent experience I believe that this phenomenon occurs more frequently than has previously been appreciated and may assume significant clinical importance in many cases. This report reviews the spectrum of the phenomenon of systemic-pulmonary vascular connection, particularly with regard to its occurrence and recognition in the adult age group. A number of illustrative cases are reported and the pertinent literature is reviewed.", "contents": "Communication between the pulmonary and systemic circulations. Communications between the pulmonary and systemic circulation occur normally and also in association with a number of pathological entities. On the basis of recent experience I believe that this phenomenon occurs more frequently than has previously been appreciated and may assume significant clinical importance in many cases. This report reviews the spectrum of the phenomenon of systemic-pulmonary vascular connection, particularly with regard to its occurrence and recognition in the adult age group. A number of illustrative cases are reported and the pertinent literature is reviewed."} {"id": "PMID:1267908", "title": "Myocardial protection during aortic valve replacement.", "content": "The results following aortic valve replacement (AVR) were compared in 40 patients in whom the myocardium was protected by topical hypothermic arrest or continuous coronary perfusion with sustained electrical fibrillation (Group A) and 40 similar patients in whom the hearts were also continuously perfused but were kept in the beating state (Group B). The operative mortality was not greatly different between the two groups, being 10 and 5%, respectively. The postperfusion cardiac performance was strikingly different, however. Seventeen patients (43%) in Group A required inotropic support, while this was necessary in only 1 patient (3%) in Group B. In this instance, recurrent ventricular fibrillation persisted despite attempts at reversion. These data show that the myocardium is preserved best during AVR when continuous coronary perfusion is used and the heart is maintained in the beating state.", "contents": "Myocardial protection during aortic valve replacement. The results following aortic valve replacement (AVR) were compared in 40 patients in whom the myocardium was protected by topical hypothermic arrest or continuous coronary perfusion with sustained electrical fibrillation (Group A) and 40 similar patients in whom the hearts were also continuously perfused but were kept in the beating state (Group B). The operative mortality was not greatly different between the two groups, being 10 and 5%, respectively. The postperfusion cardiac performance was strikingly different, however. Seventeen patients (43%) in Group A required inotropic support, while this was necessary in only 1 patient (3%) in Group B. In this instance, recurrent ventricular fibrillation persisted despite attempts at reversion. These data show that the myocardium is preserved best during AVR when continuous coronary perfusion is used and the heart is maintained in the beating state."} {"id": "PMID:1267909", "title": "Aortic valve replacement without left heart decompression.", "content": "Conventionally, during aortic valve replacement the left ventricle is vented to achieve a dry field, remove air, and prevent ventricular distention. This report demonstrates the feasibility of performing aortic valve replacement without cannulation of either the left ventricle or the left atrium. The technique has been utilized in 54 patients with 1 early death due to pulmonary embolism and 1 late death presumably secondary to ventricular arrhythmias.", "contents": "Aortic valve replacement without left heart decompression. Conventionally, during aortic valve replacement the left ventricle is vented to achieve a dry field, remove air, and prevent ventricular distention. This report demonstrates the feasibility of performing aortic valve replacement without cannulation of either the left ventricle or the left atrium. The technique has been utilized in 54 patients with 1 early death due to pulmonary embolism and 1 late death presumably secondary to ventricular arrhythmias."} {"id": "PMID:1267910", "title": "A temporary catheter-tip aortic valve: hemodynamic effects on experimental acute aortic insufficiency.", "content": "A catheter-mounted polyurethane cusp was designed to act as a temporary prosthetic aortic valve in the ascending aorta. Acute aortic insufficiency was created in 15 dogs by transventricular tearing of the two aortic valve leaflets with a wire hook. Hemodynamic variables were measured during aortic insufficiency and with the prosthetic valve in place. Comparison of the values showed that the prosthesis functioned as a competent aortic valve. Aortic diastolic pressure increased by 62 +/- 42%, pulse pressure was lowered by 44 +/- 9%, and left ventricular end-diastolic pressure decreased by 45 +/- 18%. Neither cardiac output, coronary blood flow, nor peak systolic pressure was significantly altered. The observed hemodynamic improvement and the simplicity of the design and application suggest that the prosthetic aortic valve may be applicable in the temporary treatment of decompensated aortic insufficiency.", "contents": "A temporary catheter-tip aortic valve: hemodynamic effects on experimental acute aortic insufficiency. A catheter-mounted polyurethane cusp was designed to act as a temporary prosthetic aortic valve in the ascending aorta. Acute aortic insufficiency was created in 15 dogs by transventricular tearing of the two aortic valve leaflets with a wire hook. Hemodynamic variables were measured during aortic insufficiency and with the prosthetic valve in place. Comparison of the values showed that the prosthesis functioned as a competent aortic valve. Aortic diastolic pressure increased by 62 +/- 42%, pulse pressure was lowered by 44 +/- 9%, and left ventricular end-diastolic pressure decreased by 45 +/- 18%. Neither cardiac output, coronary blood flow, nor peak systolic pressure was significantly altered. The observed hemodynamic improvement and the simplicity of the design and application suggest that the prosthetic aortic valve may be applicable in the temporary treatment of decompensated aortic insufficiency."} {"id": "PMID:1267911", "title": "The source of coronary perfusion during partial bypass for extracorporeal membrane oxygenation (ECMO).", "content": "The proper siting of cannulas to return oxygenated blood to patients on long-term membrane oxygenator support is as yet undecided. This experimental study on adult sheep shows the problems of obtaining perfusion of the coronary arterial tree when blood is returned to the ascending aorta. Our 11 experiments demonstrate that the coronary arterial tree is perfused with blood ejected from the left ventricle except during very high bypass flows (85% bypass) or when the aortic valve is rendered incompetent.", "contents": "The source of coronary perfusion during partial bypass for extracorporeal membrane oxygenation (ECMO). The proper siting of cannulas to return oxygenated blood to patients on long-term membrane oxygenator support is as yet undecided. This experimental study on adult sheep shows the problems of obtaining perfusion of the coronary arterial tree when blood is returned to the ascending aorta. Our 11 experiments demonstrate that the coronary arterial tree is perfused with blood ejected from the left ventricle except during very high bypass flows (85% bypass) or when the aortic valve is rendered incompetent."} {"id": "PMID:1267912", "title": "The effect of simultaneous administration of levarterenol and phentolamine on renal blood flow.", "content": "The effect of simultaneous administration of levarterenol and phentolamine upon renal blood flow was studied over a 3-hour period in 22 mongrel dogs. The infusion of levarterenol alone produced a fall in renal blood flow that ranged from 28 to 58% from the baseline value. When both drugs were administered simultaneously, renal flow fell only 17 to 22% from baseline (p less than 0.05). From these studies we conclude that the simultaneous administration of levarterenol and phentolamine in optimal ratios maintains renal blood flow near baseline levels.", "contents": "The effect of simultaneous administration of levarterenol and phentolamine on renal blood flow. The effect of simultaneous administration of levarterenol and phentolamine upon renal blood flow was studied over a 3-hour period in 22 mongrel dogs. The infusion of levarterenol alone produced a fall in renal blood flow that ranged from 28 to 58% from the baseline value. When both drugs were administered simultaneously, renal flow fell only 17 to 22% from baseline (p less than 0.05). From these studies we conclude that the simultaneous administration of levarterenol and phentolamine in optimal ratios maintains renal blood flow near baseline levels."} {"id": "PMID:1267913", "title": "A technique for direct measurement of left atrial pressure after cardiac operations.", "content": "A grooved director bent to a \"hockey stick\" configuration serves as an effective catheter guide to assure accurate placement of a left atrial pressure measuring catheter.", "contents": "A technique for direct measurement of left atrial pressure after cardiac operations. A grooved director bent to a \"hockey stick\" configuration serves as an effective catheter guide to assure accurate placement of a left atrial pressure measuring catheter."} {"id": "PMID:1267914", "title": "A method for insertion of a stented xenograft valve in the atrioventricular position.", "content": "To facilitate the insertion of prosthetic valves, holders are available which keep the poppet out of the area of suture insertion or keep the open ends of the struts occluded. No such holders are available for use during insertion of xenograft valves, and it seems unlikely that one could be used, for danger of damage to the valve leaflets. To obviate this problem, we have brought the flexible struts together with a suture at the time of insertion. The struts assume their original open position upon cutting the suture.", "contents": "A method for insertion of a stented xenograft valve in the atrioventricular position. To facilitate the insertion of prosthetic valves, holders are available which keep the poppet out of the area of suture insertion or keep the open ends of the struts occluded. No such holders are available for use during insertion of xenograft valves, and it seems unlikely that one could be used, for danger of damage to the valve leaflets. To obviate this problem, we have brought the flexible struts together with a suture at the time of insertion. The struts assume their original open position upon cutting the suture."} {"id": "PMID:1267915", "title": "Measured tricuspid annuloplasty: a rapid and reproducible technique.", "content": "A technique for repairing the tricuspid valve that involves principles successfully used in operative repair of the mitral valve is described. A measured orifice produces competence but not obstruction and eliminates the trial-and-error aspects of annuloplasty. The procedure can be performed with the heart beating, though it can be transiently fibrillated so that the suture may be tied without tension.", "contents": "Measured tricuspid annuloplasty: a rapid and reproducible technique. A technique for repairing the tricuspid valve that involves principles successfully used in operative repair of the mitral valve is described. A measured orifice produces competence but not obstruction and eliminates the trial-and-error aspects of annuloplasty. The procedure can be performed with the heart beating, though it can be transiently fibrillated so that the suture may be tied without tension."} {"id": "PMID:1267916", "title": "Sternal staple: simple and rapid device for closure of median sternotomy.", "content": "A new device for rapid and secure closure of median sternotomy has been developed, clinically proved, and found to be an excellent additional tool for the armamentarium of the thoracic surgeon.", "contents": "Sternal staple: simple and rapid device for closure of median sternotomy. A new device for rapid and secure closure of median sternotomy has been developed, clinically proved, and found to be an excellent additional tool for the armamentarium of the thoracic surgeon."} {"id": "PMID:1267917", "title": "Peristernal closure of median sternotomy using stainless steel bands.", "content": "Peristernal closure of median sternotomy incisions with interrupted stainless steel bands has proved to be a rapid and safe method for achieving solid internal fixation in approximation of the sternum. The method is particularly useful for obese patients undergoing sternotomy. There have been no instances of wound dehiscence using this technique, and several other advantages over standard forms of sternal closure are apparent. The method is a useful addition to the cardiac surgeon's armamentarium.", "contents": "Peristernal closure of median sternotomy using stainless steel bands. Peristernal closure of median sternotomy incisions with interrupted stainless steel bands has proved to be a rapid and safe method for achieving solid internal fixation in approximation of the sternum. The method is particularly useful for obese patients undergoing sternotomy. There have been no instances of wound dehiscence using this technique, and several other advantages over standard forms of sternal closure are apparent. The method is a useful addition to the cardiac surgeon's armamentarium."} {"id": "PMID:1267918", "title": "A modified sternal retractor.", "content": "A modification of the Favaloro sternal retractor is described that allows a singel person to operate the apparatus when elevating the sternal plate. The new retractor is also easier on the sternum because of its blunter teeth.", "contents": "A modified sternal retractor. A modification of the Favaloro sternal retractor is described that allows a singel person to operate the apparatus when elevating the sternal plate. The new retractor is also easier on the sternum because of its blunter teeth."} {"id": "PMID:1267919", "title": "Survival following free rupture of left ventricular aneurysm: report of a case.", "content": "A 50-year-old man sustained free rupture of the left ventricle four weeks following a massive anterior myocardial infarction. The rupture occurred at the junction between a bulging left ventricular aneurysm that was not yet fibrotic and normal myocardium without evidence of fresh myocardial infarction. Accurate preoperative diagnosis aided by echocardiography and right heart catheterization made possible a planned surgical approach. Postoperative support with intraaortic balloon pumping appeared to be beneficial in maintaining statisfactory cardiac function until an adequate stroke volume could be reestablished, presumably by an increase in left ventricular volume.", "contents": "Survival following free rupture of left ventricular aneurysm: report of a case. A 50-year-old man sustained free rupture of the left ventricle four weeks following a massive anterior myocardial infarction. The rupture occurred at the junction between a bulging left ventricular aneurysm that was not yet fibrotic and normal myocardium without evidence of fresh myocardial infarction. Accurate preoperative diagnosis aided by echocardiography and right heart catheterization made possible a planned surgical approach. Postoperative support with intraaortic balloon pumping appeared to be beneficial in maintaining statisfactory cardiac function until an adequate stroke volume could be reestablished, presumably by an increase in left ventricular volume."} {"id": "PMID:1267920", "title": "Aneurysm of the main pulmonary artery: long-term survival after aneurysmorrhaphy and closure of a ventricular septal defect.", "content": "Pulmonary artery aneurysm (PAA) usually carries an ominous prognosis due to the associated pulmonary hypertension. Six years ago a patient with a PAA secondary to cystic medial necrosis and pulmonary hypertension due to a ventricular septal defect (VSD) was treated by aneurysmorrhaphy and closure of the VSD. Although the patient had early postoperative cardiac failure, his cardiopulmonary status stabilized, and he has done well without recurrence of his aneurysm or cardiac failure. This report summarizes the patient's clinical course, operative treatment, and long-term follow-up.", "contents": "Aneurysm of the main pulmonary artery: long-term survival after aneurysmorrhaphy and closure of a ventricular septal defect. Pulmonary artery aneurysm (PAA) usually carries an ominous prognosis due to the associated pulmonary hypertension. Six years ago a patient with a PAA secondary to cystic medial necrosis and pulmonary hypertension due to a ventricular septal defect (VSD) was treated by aneurysmorrhaphy and closure of the VSD. Although the patient had early postoperative cardiac failure, his cardiopulmonary status stabilized, and he has done well without recurrence of his aneurysm or cardiac failure. This report summarizes the patient's clinical course, operative treatment, and long-term follow-up."} {"id": "PMID:1267923", "title": "Binocular fixation pattern.", "content": "The binocular fixation pattern (BFP) is a convenient clinical test that may be used to diagnose strabismic amblyopia in children who are too young to cooperate with conventional testing of visual acuity. A retrospective analysis of amblyopic and nonamblyopic patients with esotropia and exotropia demonstrates the effectiveness of the BFP in detecting strabismic amblyopia in children under 4 years of age. Amblyopic patients with either esotropia or exotropia reliably demonstrate strong grades of preference. Nonamblyopic patients with esotropia or exotropia usually demonstrate weak grades of fixation preference, with the important exception that most patients with small angles of esotropia have strong fixation preference even in the absence of amblyopia.", "contents": "Binocular fixation pattern. The binocular fixation pattern (BFP) is a convenient clinical test that may be used to diagnose strabismic amblyopia in children who are too young to cooperate with conventional testing of visual acuity. A retrospective analysis of amblyopic and nonamblyopic patients with esotropia and exotropia demonstrates the effectiveness of the BFP in detecting strabismic amblyopia in children under 4 years of age. Amblyopic patients with either esotropia or exotropia reliably demonstrate strong grades of preference. Nonamblyopic patients with esotropia or exotropia usually demonstrate weak grades of fixation preference, with the important exception that most patients with small angles of esotropia have strong fixation preference even in the absence of amblyopia."} {"id": "PMID:1267924", "title": "Carcinoembryonic antigen. Its role in the evaluation of intraocular malignant tumors.", "content": "Plasma carcinoembryonic antigen (CEA) was studied in 60 patients with histologically confirmed intraocular neoplasms including 56 malignant melanomas of the uvea and four metastatic tumors to the choroid. While 45% of the patients with primary uveal melanomas, as well as 75% of the patients with metastatic disease demonstrated elevated plasma CEA levels, both patients who exhibited metastatic lesions of entodermal origin demonstrated plasma CEA values that clearly fell into a separate, highly elevated category, consistent with metastatic disease or pancreatic or colorectal carcinoma. Thus, in the patient seen with a nonpigmented choroidal mass that may represent either a choroidal hemangioma, amelanotic melanoma, or metastatic tumor, plasma CEA levels may be useful in the differential diagnosis. If the clinician suspects a metastatic tumor from an occult primary site, highly elevated CEA levels may indicate that the lesion is of entodermal origin.", "contents": "Carcinoembryonic antigen. Its role in the evaluation of intraocular malignant tumors. Plasma carcinoembryonic antigen (CEA) was studied in 60 patients with histologically confirmed intraocular neoplasms including 56 malignant melanomas of the uvea and four metastatic tumors to the choroid. While 45% of the patients with primary uveal melanomas, as well as 75% of the patients with metastatic disease demonstrated elevated plasma CEA levels, both patients who exhibited metastatic lesions of entodermal origin demonstrated plasma CEA values that clearly fell into a separate, highly elevated category, consistent with metastatic disease or pancreatic or colorectal carcinoma. Thus, in the patient seen with a nonpigmented choroidal mass that may represent either a choroidal hemangioma, amelanotic melanoma, or metastatic tumor, plasma CEA levels may be useful in the differential diagnosis. If the clinician suspects a metastatic tumor from an occult primary site, highly elevated CEA levels may indicate that the lesion is of entodermal origin."} {"id": "PMID:1267925", "title": "The iris-plane (Copeland) pseudophakos.", "content": "The iris-plane (Copeland) pseudophakos was evaluated in two 81-case surgical series. An early series consisted of the first 81 operations performed in the Miami community before a temporary moratorium on Oct 1, 1969. This series was compared with the first 81 operations performed after the moratorium was lifted on Oct 1, 1971. The follow-up period of those available for study was 63 months in the early series and 19 months in the later series. Objectivity was assured since all surgery was performed by one author (N.S.J.) and all examinations performed by the other author (L.R.D.). Visual acuity of 6/12 or better was obtained in approximately 80% of patients. The most frequent problems encountered were recurrent iritis and cystoid macular edema. The optic benefit was apparent in this elderly group of patients who avoided the optical problems of aphakia.", "contents": "The iris-plane (Copeland) pseudophakos. The iris-plane (Copeland) pseudophakos was evaluated in two 81-case surgical series. An early series consisted of the first 81 operations performed in the Miami community before a temporary moratorium on Oct 1, 1969. This series was compared with the first 81 operations performed after the moratorium was lifted on Oct 1, 1971. The follow-up period of those available for study was 63 months in the early series and 19 months in the later series. Objectivity was assured since all surgery was performed by one author (N.S.J.) and all examinations performed by the other author (L.R.D.). Visual acuity of 6/12 or better was obtained in approximately 80% of patients. The most frequent problems encountered were recurrent iritis and cystoid macular edema. The optic benefit was apparent in this elderly group of patients who avoided the optical problems of aphakia."} {"id": "PMID:1267926", "title": "Fluorophotometry and the rate of aqueous flow in man. II. Primary open angle glaucoma.", "content": "By fluorophotometry, the aqueous outflow rates of 38 eyes of 22 patients with definite or suspected primary open angle glaucoma, who were not receiving therapy, were determined. Although the values obtained do not differ from normal, the factors that modify or control the flow rate are different in normal and glaucomatous eyes. The flow rate decreases as the pressure increases in the glaucomatous group but not in the normal group. The flow rate increases with anterior chamber depth and decreases with age in the normal group but not in the glaucomatous group. The fluorescein decay constant is a measure of the movement of fluorescein from the cornea to the aqueous. This constant increases as the pressure increases in the glaucomatous group but not in the normal group.", "contents": "Fluorophotometry and the rate of aqueous flow in man. II. Primary open angle glaucoma. By fluorophotometry, the aqueous outflow rates of 38 eyes of 22 patients with definite or suspected primary open angle glaucoma, who were not receiving therapy, were determined. Although the values obtained do not differ from normal, the factors that modify or control the flow rate are different in normal and glaucomatous eyes. The flow rate decreases as the pressure increases in the glaucomatous group but not in the normal group. The flow rate increases with anterior chamber depth and decreases with age in the normal group but not in the glaucomatous group. The fluorescein decay constant is a measure of the movement of fluorescein from the cornea to the aqueous. This constant increases as the pressure increases in the glaucomatous group but not in the normal group."} {"id": "PMID:1267927", "title": "The effect of the honeycomb on glare function.", "content": "Patients with certain forms of cataract or corneal disease have diminished visual acuity in a brightly lit environment. This is due to increased light scattering, which causes increased glare sensitivity. In a series of experiments, a sequence of bottles containing a suspension of latex particles was used to simulate the effect of different degrees of cataract and corneal edema on visual acuity. It was shown that anodized honeycombs could substantially improve visual acuity through the latex-containing bottles. The mechanism of visual improvement was shown to be by reduction of glare and increase in contrast.", "contents": "The effect of the honeycomb on glare function. Patients with certain forms of cataract or corneal disease have diminished visual acuity in a brightly lit environment. This is due to increased light scattering, which causes increased glare sensitivity. In a series of experiments, a sequence of bottles containing a suspension of latex particles was used to simulate the effect of different degrees of cataract and corneal edema on visual acuity. It was shown that anodized honeycombs could substantially improve visual acuity through the latex-containing bottles. The mechanism of visual improvement was shown to be by reduction of glare and increase in contrast."} {"id": "PMID:1267928", "title": "Cyclic esotropia developing after sttstrabismus surgery.", "content": "Cyclic or alternate-day esotropia developed in a patient following strabismus surgery for intermittent exotropia, which resulted in a small overresponse or overcorrection. Surgery, aimed at the deviation on the esotropic days, resulted in binocularity and loss of the cyclic pattern.", "contents": "Cyclic esotropia developing after sttstrabismus surgery. Cyclic or alternate-day esotropia developed in a patient following strabismus surgery for intermittent exotropia, which resulted in a small overresponse or overcorrection. Surgery, aimed at the deviation on the esotropic days, resulted in binocularity and loss of the cyclic pattern."} {"id": "PMID:1267929", "title": "Reversible unilateral lens opacities in a diabetic patient.", "content": "Following one month of poor diabetic control, a 54-year-old patient presented with a unilateral posterior subcapsular cataract, consisting of numerous fine, feathery, streak-like opacities radiating from a dense, round, central, posterior, subcapsular plaque. Except for extensive pseudoexfoliation, the fellow lens was clear. After a subsequent week of strict diabetic control, the feathery streak-like opacities had almost disappeared. The findings are discussed in relation to the experimentally induced sugar cataract in which sugar alcohol accumulation and subsequent lens swelling result in a potentially reversible lens opacification.", "contents": "Reversible unilateral lens opacities in a diabetic patient. Following one month of poor diabetic control, a 54-year-old patient presented with a unilateral posterior subcapsular cataract, consisting of numerous fine, feathery, streak-like opacities radiating from a dense, round, central, posterior, subcapsular plaque. Except for extensive pseudoexfoliation, the fellow lens was clear. After a subsequent week of strict diabetic control, the feathery streak-like opacities had almost disappeared. The findings are discussed in relation to the experimentally induced sugar cataract in which sugar alcohol accumulation and subsequent lens swelling result in a potentially reversible lens opacification."} {"id": "PMID:1267930", "title": "Funduscopic appearance of papilledema with optic tract atrophy.", "content": "In a child with a hypothalamic glioma, elevated intracranial pressure and retrograde optic tract atrophy produced distinctive patterns of papilledema and disc pallor in each eye. On the side of the tract lesion, the disc was swollen nasally and was pale temporally. In the contralateral fundus, the swollen optic disc was bisected horizontally by a pale atrophic band. These funduscopic signs exemplify a rare instance in neuro-ophthalmologic diagnosis wherein specific lateralizing and localizing information can be deduced solely from the appearance of papilledema.", "contents": "Funduscopic appearance of papilledema with optic tract atrophy. In a child with a hypothalamic glioma, elevated intracranial pressure and retrograde optic tract atrophy produced distinctive patterns of papilledema and disc pallor in each eye. On the side of the tract lesion, the disc was swollen nasally and was pale temporally. In the contralateral fundus, the swollen optic disc was bisected horizontally by a pale atrophic band. These funduscopic signs exemplify a rare instance in neuro-ophthalmologic diagnosis wherein specific lateralizing and localizing information can be deduced solely from the appearance of papilledema."} {"id": "PMID:1267931", "title": "Protozoan feeding and bacterial wall growth.", "content": "Monod's model is often assumed to describe the kinetics of feeding of a protozoan population on a bacterial population in a chemostat. An earlier study (J. L. Jost et al., J. Bacteriol., 113, 84 (1973)) of the feeding of Tetrahymena pyriformis on either Escherichia coli or Azotobacter vinelandii found that this model correctly predicted the occurrence of sustained oscillations of population densities but made predictions of minimum bacterial population densities that were much smaller than those observed. The earlier study removed the discrepancy between the model and data by replacing Monod's model with a different model. It is shown in the present study that the discrepancy can be explained equally as well if Monod's model for the feed relation is retained and if, in addition, growth of bacteria on the chemostat walls is allowed for in the model equations.", "contents": "Protozoan feeding and bacterial wall growth. Monod's model is often assumed to describe the kinetics of feeding of a protozoan population on a bacterial population in a chemostat. An earlier study (J. L. Jost et al., J. Bacteriol., 113, 84 (1973)) of the feeding of Tetrahymena pyriformis on either Escherichia coli or Azotobacter vinelandii found that this model correctly predicted the occurrence of sustained oscillations of population densities but made predictions of minimum bacterial population densities that were much smaller than those observed. The earlier study removed the discrepancy between the model and data by replacing Monod's model with a different model. It is shown in the present study that the discrepancy can be explained equally as well if Monod's model for the feed relation is retained and if, in addition, growth of bacteria on the chemostat walls is allowed for in the model equations."} {"id": "PMID:1267932", "title": "Cooling rate effects in thermoluminescence dosimetry grade lithium flouride. Implications for practical dosimetry.", "content": "A systematic investigation of the effects of cooling rates in the range of 10(-1) to 2 X 10(5) degrees C min-1 applied to TLD-700, LiF thermoluminescence dosemeters has shown that the 'transfer sensitivity' effect observed by Booth, Johnson and Attix (1972) is only of importance for cooling rates greater than 10(3) degrees C min-1. Although it is concluded that for practical dosimetry purposes the effect may be ignored it is not clear why Booth et al. observed such large changes and until this discrepancy is explained it is recommended that a low temperature pre-irradiation anneal should be used.", "contents": "Cooling rate effects in thermoluminescence dosimetry grade lithium flouride. Implications for practical dosimetry. A systematic investigation of the effects of cooling rates in the range of 10(-1) to 2 X 10(5) degrees C min-1 applied to TLD-700, LiF thermoluminescence dosemeters has shown that the 'transfer sensitivity' effect observed by Booth, Johnson and Attix (1972) is only of importance for cooling rates greater than 10(3) degrees C min-1. Although it is concluded that for practical dosimetry purposes the effect may be ignored it is not clear why Booth et al. observed such large changes and until this discrepancy is explained it is recommended that a low temperature pre-irradiation anneal should be used."} {"id": "PMID:1267933", "title": "Observations on the combined effect of ultrasound and x-rays on the growth of the roots of Zea mays.", "content": "The roots of Zea mays seedlings were exposed to ultrasonic radiations (1 MHz) of intensities in the range of 0-1-0-8 W cm-2 (pulsed or continuous modes) for times between 2 and 60 min, together with an X-ray dose of 775 rad which was given before, after or simultaneously with the ultrasound. These experiments have shown that ultrasound and X-rays seem to act independently of each other, suggesting that the mechanism of damage due to X-rays is different from that due to ultrasound. An increase in the X-ray effectiveness under the action of ultrasound, as reported by various authors who worked with different tissues, has not been found.", "contents": "Observations on the combined effect of ultrasound and x-rays on the growth of the roots of Zea mays. The roots of Zea mays seedlings were exposed to ultrasonic radiations (1 MHz) of intensities in the range of 0-1-0-8 W cm-2 (pulsed or continuous modes) for times between 2 and 60 min, together with an X-ray dose of 775 rad which was given before, after or simultaneously with the ultrasound. These experiments have shown that ultrasound and X-rays seem to act independently of each other, suggesting that the mechanism of damage due to X-rays is different from that due to ultrasound. An increase in the X-ray effectiveness under the action of ultrasound, as reported by various authors who worked with different tissues, has not been found."} {"id": "PMID:1267934", "title": "The andrenocortical homolog in the lake sturgeon, acipenser fulvescens rafinesque.", "content": "The adrenocortical homolog in the chondrostean fish, Acipenser fulvescens, is confined within yellow corpuscles located at the dorsal junction of the two kidneys near the cardinal veins. The concentration and distribution of this tissue in chondrosteans appear to be a condition intermediate between that of cyclostomes and teleosts. The homology of this tissue to adrenocortical tissue of higher vertebrates is demonstrated in its delta5-3beta-hydroxysteroid dehydrogenase activity and the ultrastructure of the cells. The cells contain large lipid droplets and an abundance of smooth endoplasmic reticulum and mitochondria. The abundance of smooth endoplasmic reticulum, a large Golgi apparatus and an extensive elaboration of the plasma membrane suggest the high degree of steroidogenic activity of these cells. Apposed plasma membranes make contacts through the unique cell contacts described in the adrenocortical cells of mammals (Friend and Gilula, '72). The Golgi apparatus is described as a most conspicuous component of the cytoplasm and is presented as further evidence for the important involvement of this organelle in corticosteroidogenesis in vertebrates. These morphological observations are discussed in relation to the known secretory products of this tissue in the sturgeon, and it is suggested that there is a need for further examination of the corticosteroids produced by lower vertebrates.", "contents": "The andrenocortical homolog in the lake sturgeon, acipenser fulvescens rafinesque. The adrenocortical homolog in the chondrostean fish, Acipenser fulvescens, is confined within yellow corpuscles located at the dorsal junction of the two kidneys near the cardinal veins. The concentration and distribution of this tissue in chondrosteans appear to be a condition intermediate between that of cyclostomes and teleosts. The homology of this tissue to adrenocortical tissue of higher vertebrates is demonstrated in its delta5-3beta-hydroxysteroid dehydrogenase activity and the ultrastructure of the cells. The cells contain large lipid droplets and an abundance of smooth endoplasmic reticulum and mitochondria. The abundance of smooth endoplasmic reticulum, a large Golgi apparatus and an extensive elaboration of the plasma membrane suggest the high degree of steroidogenic activity of these cells. Apposed plasma membranes make contacts through the unique cell contacts described in the adrenocortical cells of mammals (Friend and Gilula, '72). The Golgi apparatus is described as a most conspicuous component of the cytoplasm and is presented as further evidence for the important involvement of this organelle in corticosteroidogenesis in vertebrates. These morphological observations are discussed in relation to the known secretory products of this tissue in the sturgeon, and it is suggested that there is a need for further examination of the corticosteroids produced by lower vertebrates."} {"id": "PMID:1267935", "title": "A portable beam for mounting intensive care devices.", "content": "A portable beam for accommodating many devices necessary to intensive care is described. It can be clamped to bedheads, trolley tops, working surfaces, or between intravenous stands and thus neatly converts an ordinary bed-space into an intensive care area.", "contents": "A portable beam for mounting intensive care devices. A portable beam for accommodating many devices necessary to intensive care is described. It can be clamped to bedheads, trolley tops, working surfaces, or between intravenous stands and thus neatly converts an ordinary bed-space into an intensive care area."} {"id": "PMID:1267936", "title": "Local anesthesia for suspension microlaryngoscopy.", "content": "Despite the strong trend toward use of general anesthesia for laryngoscopy, local anesthesia retains inherent advantages from the standpoint of patient safety and maintenance of physiologic function of the larynx during endoscopy. Topical anesthesia produces incomplete sensory blockade and is unsatisfactory for suspension laryngoscopy. A method of infiltration anesthesia is described whereby profound anesthesia of the base of the tongue, valleculae, and larynx can be achieved to allow suspension laryngoscopy.", "contents": "Local anesthesia for suspension microlaryngoscopy. Despite the strong trend toward use of general anesthesia for laryngoscopy, local anesthesia retains inherent advantages from the standpoint of patient safety and maintenance of physiologic function of the larynx during endoscopy. Topical anesthesia produces incomplete sensory blockade and is unsatisfactory for suspension laryngoscopy. A method of infiltration anesthesia is described whereby profound anesthesia of the base of the tongue, valleculae, and larynx can be achieved to allow suspension laryngoscopy."} {"id": "PMID:1267947", "title": "[Systemic candidiasis with localization in the brain. Anatomo-clinical study of 5 cases].", "content": "Central nervous system involvement in Candida septicaemia is rare and not more than four cases have been published in Brazil. Five new cases of systemic candidiasis with cerebral lesions are reported. All patients (four adults and a child) had serious underlying diseases and were submitted to heavy long-term antibiotic therapy with multiple drugs. Seizures in one case and neck stiffness in another were the only neurologic signs that could be attributed to candidiasis. In no case were the lesions severe enough to be considered an immediate cause of death. In three patients, no macroscopic changes were evident in the brain, but microabscesses and granulomata were observed on microscopical examination; another patient had two gross areas with necrotic and haemorrhagic appearance in the cerebral hemispheres; the child had only two microscopic granulomata. The aetiological agent was demonstrated by Grocott's methenamine silver technique in all cases. Involvement of organs other than the central nervous system could be demonstrated in three autopsies. Discussion is confined mainly to such aspects as the contributory factors in the pathogenesis of systemic candidiasis as well as the marked rise in the incidence of this condition in the past few decades. It is suggested that the frequence of monilial septicaemia in Brazil may be far more serious than apparent from the scarcity of reported cases.", "contents": "[Systemic candidiasis with localization in the brain. Anatomo-clinical study of 5 cases]. Central nervous system involvement in Candida septicaemia is rare and not more than four cases have been published in Brazil. Five new cases of systemic candidiasis with cerebral lesions are reported. All patients (four adults and a child) had serious underlying diseases and were submitted to heavy long-term antibiotic therapy with multiple drugs. Seizures in one case and neck stiffness in another were the only neurologic signs that could be attributed to candidiasis. In no case were the lesions severe enough to be considered an immediate cause of death. In three patients, no macroscopic changes were evident in the brain, but microabscesses and granulomata were observed on microscopical examination; another patient had two gross areas with necrotic and haemorrhagic appearance in the cerebral hemispheres; the child had only two microscopic granulomata. The aetiological agent was demonstrated by Grocott's methenamine silver technique in all cases. Involvement of organs other than the central nervous system could be demonstrated in three autopsies. Discussion is confined mainly to such aspects as the contributory factors in the pathogenesis of systemic candidiasis as well as the marked rise in the incidence of this condition in the past few decades. It is suggested that the frequence of monilial septicaemia in Brazil may be far more serious than apparent from the scarcity of reported cases."} {"id": "PMID:1267950", "title": "[Acute paraplegia due to embolism from nucleus pulposus tissue (author's transl)].", "content": "Typical anterior spinal artery syndrome with initially severe pain and paraplegia with sensory disturbances occurred after a fall in a 36-year-old man with a history of lumbago. Multiple emboli of fibrocartilaginous material with nucleus pulposus cells were found in the foci of myelomalacia. The embolism of nucleus pulposus tissue originating from Schmorl's nodules was probably carried via the blood vessels of the neighbouring vertebral bodies with retrograde flow through the perispinal venous plexus into spinal cord veins and hence into the arteries of the spinal cord via veno-arterial anastomoses. A transitory increase in intra-abdominal pressure was probably the cause of the inversion of venous flow.", "contents": "[Acute paraplegia due to embolism from nucleus pulposus tissue (author's transl)]. Typical anterior spinal artery syndrome with initially severe pain and paraplegia with sensory disturbances occurred after a fall in a 36-year-old man with a history of lumbago. Multiple emboli of fibrocartilaginous material with nucleus pulposus cells were found in the foci of myelomalacia. The embolism of nucleus pulposus tissue originating from Schmorl's nodules was probably carried via the blood vessels of the neighbouring vertebral bodies with retrograde flow through the perispinal venous plexus into spinal cord veins and hence into the arteries of the spinal cord via veno-arterial anastomoses. A transitory increase in intra-abdominal pressure was probably the cause of the inversion of venous flow."} {"id": "PMID:1267951", "title": "[Surgical treatment of ventricular aneurysm: an analysis of post-resection haemodynamic changes (author's transl)].", "content": "Of 500 patients with angiographically proven myocardial infarction 75 had a left ventricular aneurysm. 25 of them subsequently had resection of the aneurysm. Postoperative studies revealed marked improvement of symptoms. Pulmonary arterial pressure was significantly decreased at rest (from 28 to 20 mm Hg) and on exercise (from 58 to 35 mm Hg). There was a reduction in left ventricular end-diastolic volume (from 247 to 1.54 ml/1.73 m2) and a raised ejection fraction (from 36 to 59%). Good results were obtained especially in those patients who had congestive heart failure due to paradoxical systolic expansion of the ventricular wall and (or) secondary reversible damage in the remaining viable myocardium. Left ventricular aneurysms should be suspected after myocardial infarction when there is left ventricular failure and an increase in heart size.", "contents": "[Surgical treatment of ventricular aneurysm: an analysis of post-resection haemodynamic changes (author's transl)]. Of 500 patients with angiographically proven myocardial infarction 75 had a left ventricular aneurysm. 25 of them subsequently had resection of the aneurysm. Postoperative studies revealed marked improvement of symptoms. Pulmonary arterial pressure was significantly decreased at rest (from 28 to 20 mm Hg) and on exercise (from 58 to 35 mm Hg). There was a reduction in left ventricular end-diastolic volume (from 247 to 1.54 ml/1.73 m2) and a raised ejection fraction (from 36 to 59%). Good results were obtained especially in those patients who had congestive heart failure due to paradoxical systolic expansion of the ventricular wall and (or) secondary reversible damage in the remaining viable myocardium. Left ventricular aneurysms should be suspected after myocardial infarction when there is left ventricular failure and an increase in heart size."} {"id": "PMID:1267962", "title": "Ultrastructure and cytochemistry of bone marrow granulocytes in culture.", "content": "Leukocytes from human bone marrow, grown in clonal cell culture with methylcellulose medium, were characterized ultrastructurally and cytochemically, utilizing techniques for demonstrating peroxidase, acid phosphatase, dialyzed iron reactive mucosubstance, antimonate reactive cation and Concanavalin A surface receptors. Neutrophils and eosinophils were identified in culture specimens and in many respects resembled those seen in direct marrow specimens. Cultured neutrophils, however, did not develop secondary (specific) granules and the crystalloids of eosinophil granules appeared abnormal. The strong reaction of neutrophil primary granules with antimonate and dialyzed iron afforded differentiation from unreactive monocyte-macrophage granules and thus distinguished these cell types in culture. Basophils were observed in morphologic preparations and their granules stained most intensely for acid mucosubstance with the dialyzed iron method.", "contents": "Ultrastructure and cytochemistry of bone marrow granulocytes in culture. Leukocytes from human bone marrow, grown in clonal cell culture with methylcellulose medium, were characterized ultrastructurally and cytochemically, utilizing techniques for demonstrating peroxidase, acid phosphatase, dialyzed iron reactive mucosubstance, antimonate reactive cation and Concanavalin A surface receptors. Neutrophils and eosinophils were identified in culture specimens and in many respects resembled those seen in direct marrow specimens. Cultured neutrophils, however, did not develop secondary (specific) granules and the crystalloids of eosinophil granules appeared abnormal. The strong reaction of neutrophil primary granules with antimonate and dialyzed iron afforded differentiation from unreactive monocyte-macrophage granules and thus distinguished these cell types in culture. Basophils were observed in morphologic preparations and their granules stained most intensely for acid mucosubstance with the dialyzed iron method."} {"id": "PMID:1267964", "title": "Confirmation of the human thymidine kinase locus, 17q21 leads to 17qter, by means of a man-mouse somatic cell hybrid, D98/AH-2 X LMTK-Cl-lD.", "content": "A large metacentric marker chromosome, m20, in a line of human D98/AH-2 cells was identified by Q bands as being a translocation (1;17)(p36;q21). This was confirmed by means of somatic cell hybridization between D98/AH-2 and thymidine kinase (TK) deficient mouse cells. The hybrid clones by HAT selective system retained m20, indicating the presence of TK locus on this chromosome. The results also provide evidence that TK gene is located on the distal region of the breakpoint in 17q21 but not on 17q21 leads to 17pter.", "contents": "Confirmation of the human thymidine kinase locus, 17q21 leads to 17qter, by means of a man-mouse somatic cell hybrid, D98/AH-2 X LMTK-Cl-lD. A large metacentric marker chromosome, m20, in a line of human D98/AH-2 cells was identified by Q bands as being a translocation (1;17)(p36;q21). This was confirmed by means of somatic cell hybridization between D98/AH-2 and thymidine kinase (TK) deficient mouse cells. The hybrid clones by HAT selective system retained m20, indicating the presence of TK locus on this chromosome. The results also provide evidence that TK gene is located on the distal region of the breakpoint in 17q21 but not on 17q21 leads to 17pter."} {"id": "PMID:1267965", "title": "[Epithelial invasion of the anterior chamber. Apropos of eight cases operated on using Maumenee's technic].", "content": "Eight cases of epithelial downgrowth have been operated on by Maumenee's technique. Two cases were considered entirely successful, using the stringent criteria of Maumenee. Four other cases were partly successful maintaining a visual acuity of 20/300-20/400 without any recurrence, and normal ocular pressure or glaucoma controlled by topical medication. The value of Maumenee's surgical technique in these cases is obvious if one wishes to save these patients' eyes and keep useful vision. The only change suggested is not to treat the involved cornea by any specific procedure.", "contents": "[Epithelial invasion of the anterior chamber. Apropos of eight cases operated on using Maumenee's technic]. Eight cases of epithelial downgrowth have been operated on by Maumenee's technique. Two cases were considered entirely successful, using the stringent criteria of Maumenee. Four other cases were partly successful maintaining a visual acuity of 20/300-20/400 without any recurrence, and normal ocular pressure or glaucoma controlled by topical medication. The value of Maumenee's surgical technique in these cases is obvious if one wishes to save these patients' eyes and keep useful vision. The only change suggested is not to treat the involved cornea by any specific procedure."} {"id": "PMID:1267966", "title": "Utrastructure of the cement gland of Xenopus laevis.", "content": "To establish a morphological baseline for experimental studies of differentiation using the cement gland as a model, the following observations are added to those on record. The elongated cells of Xenopus laevis cement glands have an internal organization displaying five distinct zones differing in structure and specialized function. The apical zone contains packed secretion vesicles apparently belonging to two different types. The transit zone appears to be devoid of major biosynthetic activity and contains secretion vesicles migrating toward the surface. The zone of biosynthesis is typically organized in concentric regions. The very elongated nucleus lies in the next zone. Finally, the storage zone is characterized by lipid droplets and yolk platelets. Only quantitative differences are observed between cells of young and mature cement glands. Though all cells have the same general organization they may probably be divided into two subtypes according to the structure of their cytoplasm. The epithelial cells surrounding the gland differ according to their position along lateral or basal borders.", "contents": "Utrastructure of the cement gland of Xenopus laevis. To establish a morphological baseline for experimental studies of differentiation using the cement gland as a model, the following observations are added to those on record. The elongated cells of Xenopus laevis cement glands have an internal organization displaying five distinct zones differing in structure and specialized function. The apical zone contains packed secretion vesicles apparently belonging to two different types. The transit zone appears to be devoid of major biosynthetic activity and contains secretion vesicles migrating toward the surface. The zone of biosynthesis is typically organized in concentric regions. The very elongated nucleus lies in the next zone. Finally, the storage zone is characterized by lipid droplets and yolk platelets. Only quantitative differences are observed between cells of young and mature cement glands. Though all cells have the same general organization they may probably be divided into two subtypes according to the structure of their cytoplasm. The epithelial cells surrounding the gland differ according to their position along lateral or basal borders."} {"id": "PMID:1267967", "title": "Circadian influence on the frequency of labeled mitoses method in the stratified squamous epithelium of the mouse esophagus and tongue.", "content": "The frequency of labeled mitoses method (FLM) was used to study the cell kinetics in the stratified squamous epithelium of the mouse esophagus and tongue. FLMs were generated by injecting tritiated thymidine (TdR) at two different phases of the mouse circadian system: TdR was injected into one group of mice at 0900 and into a different, second group of mice at 2100. Three variables were monitored for each group; (1) the FLM, (2) the mitotic index and (3) the grain count over the labeled mitotic figures. In both the esophagus and the tongue there was a circadian rhythm in the mitotic index with the peak occurring during the first half of the diurnal phase and the trough occurring during the first half of the nocturnal phase. The FLM curves from each group revealed the following data.", "contents": "Circadian influence on the frequency of labeled mitoses method in the stratified squamous epithelium of the mouse esophagus and tongue. The frequency of labeled mitoses method (FLM) was used to study the cell kinetics in the stratified squamous epithelium of the mouse esophagus and tongue. FLMs were generated by injecting tritiated thymidine (TdR) at two different phases of the mouse circadian system: TdR was injected into one group of mice at 0900 and into a different, second group of mice at 2100. Three variables were monitored for each group; (1) the FLM, (2) the mitotic index and (3) the grain count over the labeled mitotic figures. In both the esophagus and the tongue there was a circadian rhythm in the mitotic index with the peak occurring during the first half of the diurnal phase and the trough occurring during the first half of the nocturnal phase. The FLM curves from each group revealed the following data."} {"id": "PMID:1267968", "title": "Ultrastructure of the indifferent gonad in male and female pig embryos.", "content": "Pig embryos aged 24 days were obtained from artifically inseminated sows for ultrastructural study of the indifferent gonads. Sex was identified by chromosome analysis. The gonads are composed in both sexes of three different tissues: the surface epithelium, the gonadal blastema and the mesenchyme. The surface epithelial cells contained elongate mitochondria, granular endoplasmic reticulum, free polysomes, the Golgi complex, fine filaments and coated vesicles. The primitive cords were continuous with the surface epithelium and the interior of the gonad was occupied by blastema cells. They had prominent nucleoli, elongate mitochondria, granular endoplasmic reticulum, the Golgi complex, free polysomes, some lipid droplets and occasionally circular smooth membrane profiles resembling the agranular endoplasmic reticulum. Individual primordial germ cells were seen in all parts of the gonad. They were roundish with prominent nucleoli, globular mitochondria, granular endoplasmic reticulum, free polysomes, the Golgi complex, coated vesicles, lipid droplets and dense bodies. Degenerating cells and cells having pseudopods were also encountered. In comparison to the gonad at the age of 22 days, the primordium had grown into a longitudinal roundish protrusion and the number of primoridal germ cells had increased. Histological and ultrastructural observations showed that the pig gonads at the age of 24 days were similar in both sexes.", "contents": "Ultrastructure of the indifferent gonad in male and female pig embryos. Pig embryos aged 24 days were obtained from artifically inseminated sows for ultrastructural study of the indifferent gonads. Sex was identified by chromosome analysis. The gonads are composed in both sexes of three different tissues: the surface epithelium, the gonadal blastema and the mesenchyme. The surface epithelial cells contained elongate mitochondria, granular endoplasmic reticulum, free polysomes, the Golgi complex, fine filaments and coated vesicles. The primitive cords were continuous with the surface epithelium and the interior of the gonad was occupied by blastema cells. They had prominent nucleoli, elongate mitochondria, granular endoplasmic reticulum, the Golgi complex, free polysomes, some lipid droplets and occasionally circular smooth membrane profiles resembling the agranular endoplasmic reticulum. Individual primordial germ cells were seen in all parts of the gonad. They were roundish with prominent nucleoli, globular mitochondria, granular endoplasmic reticulum, free polysomes, the Golgi complex, coated vesicles, lipid droplets and dense bodies. Degenerating cells and cells having pseudopods were also encountered. In comparison to the gonad at the age of 22 days, the primordium had grown into a longitudinal roundish protrusion and the number of primoridal germ cells had increased. Histological and ultrastructural observations showed that the pig gonads at the age of 24 days were similar in both sexes."} {"id": "PMID:1267969", "title": "Morphological changes in the trophoblast, uterus and corpus luteum during delayed implantation and implantation in the western spotted skunk.", "content": "Morphological interactions of tropholbast and uterus from stages of preimplantation and implantation were studied in 14 western spotted skunks. In addition, the granulosa lutein cells and plasma progesterone levels were studied. In animals several days from implantation the height of epithelial cells decreased, but began to increase in animals approaching implantation. During the preimplantation period a few leucocytes infiltrated the epithelium, but in animals just prior to implantation many leucocytes infiltrated the epithelium.", "contents": "Morphological changes in the trophoblast, uterus and corpus luteum during delayed implantation and implantation in the western spotted skunk. Morphological interactions of tropholbast and uterus from stages of preimplantation and implantation were studied in 14 western spotted skunks. In addition, the granulosa lutein cells and plasma progesterone levels were studied. In animals several days from implantation the height of epithelial cells decreased, but began to increase in animals approaching implantation. During the preimplantation period a few leucocytes infiltrated the epithelium, but in animals just prior to implantation many leucocytes infiltrated the epithelium."} {"id": "PMID:1267970", "title": "High-speed liquid chromatographic determination of canrenone in pharmaceutical dosage forms.", "content": "Canrenone can be determined by high-speed liquid chromatography in pharmaceutical dosage forms without interference from common excipients or degradation products. This stability-indicating assay, using o-nitroaniline as the internal standard, is rapid and accurate.", "contents": "High-speed liquid chromatographic determination of canrenone in pharmaceutical dosage forms. Canrenone can be determined by high-speed liquid chromatography in pharmaceutical dosage forms without interference from common excipients or degradation products. This stability-indicating assay, using o-nitroaniline as the internal standard, is rapid and accurate."} {"id": "PMID:1267978", "title": "Sequential chamber localization--logical approach to diagnosis in congenital heart disease.", "content": "A nomenclature is described for congenital heart disease employing sequential chamber localization. It is an eclectic system based in part upon the previous classifications of Van Praagh and Kirklin. It links together the atrial, ventricular, and arterial segments of the heart and then permits tabulation of associated anomalies. The atrial segment of the heart can exist as situs solitus, situs inversus, or situs ambiguus. Atrioventricular connexions can be concordant or discordant. In certain circumstances the terms concordant and discordant cannot be used. These are in the presence of primitive ventricle and in the presence of situs ambiguus. Alternative terms are described for these contingencies. Ventriculo-arterial connexions can be (a) normal; (b) transposition; (c) double outlet ventricle; or (d) single arterial trunk. These are defined as connexions; relations are relegated to secondary position. Associated anomalies are categorized in terms of venous return, atria, atrioventricular junction, ventricles, and great arteries. Controversial topics are discussed with regard to previous definitions.", "contents": "Sequential chamber localization--logical approach to diagnosis in congenital heart disease. A nomenclature is described for congenital heart disease employing sequential chamber localization. It is an eclectic system based in part upon the previous classifications of Van Praagh and Kirklin. It links together the atrial, ventricular, and arterial segments of the heart and then permits tabulation of associated anomalies. The atrial segment of the heart can exist as situs solitus, situs inversus, or situs ambiguus. Atrioventricular connexions can be concordant or discordant. In certain circumstances the terms concordant and discordant cannot be used. These are in the presence of primitive ventricle and in the presence of situs ambiguus. Alternative terms are described for these contingencies. Ventriculo-arterial connexions can be (a) normal; (b) transposition; (c) double outlet ventricle; or (d) single arterial trunk. These are defined as connexions; relations are relegated to secondary position. Associated anomalies are categorized in terms of venous return, atria, atrioventricular junction, ventricles, and great arteries. Controversial topics are discussed with regard to previous definitions."} {"id": "PMID:1267979", "title": "Rules for diagnosis of arterioventricular discordances and spatial identification of ventricles. Crossed great arteries and transposition of the great arteries.", "content": "Rules are presented for the diagnosis of arterioventricular discordances and the spatial position of the ventricles in these cardiopathies by means of angiocardiography and the position of cardiac catheters. Because these rules are based on previous anatomo-embryological findings, the normal development of the conus and the truncus is briefly analysed. The probable morphogenesis of this group of truncoconal cardiopathies is discussed. The fundamental process required to establish the diagnosis of these cardiopathies is as follows: 1) The truncoconal morphology is identified in the lateral projection. a) The anterior position of the pulmonary artery and its infundibulum with respect to the aorta and its infundibulum is characteristic of crossed great arteries with arterioventricular concordance or discordance. b) The anterior position of the aorta and its infundibulum with respect to the pulmonary artery and its infundibulum is characteristic of transposition of the great arteries with arterioventricular concordance or discordance. 2) Once the truncoconal morphology is identified, the use of the anteroposterior projection allows the establishment of the differential diagnosis between arterioventricular concordances and discordances, and of the spatial location of the ventricles in these entities. a) An anterior pulmonary artery directed from right to left, emerging from an infundibulum placed on the left side (anatomically right ventricle on the left) or an anterior pulmonary artery directed from left to right, arising from an infundibulum located to the right (anatomically right ventricular placed on the right), is the specific image of discordant crossed great arteries. b) An anterior pulmonary artery directed from right to left emerging from an infundibulum placed on the right side (anatomically right ventricle on the right side) or the anterior pulmonary artery directed from left to right arising from a left-sided infundibulum (anatomically right ventricle placed on the left side) is characteristic of concordant crossed great arteries. c) An anterior aorta placed to the right of the pulmonary artery and emerging from a left-sided infundibulum (anatomically right ventricle placed on the left side) or an anterior aorta placed to the left of the pulmonary artery and arising from an infundibulum placed on the right side (anatomically right ventricle placed on the right) is characteristic of discordant transposition of the great arteries. d) An anterior aorta placed to the right of the pulmonary artery emerging from a right-sided infundibulum (anatomically right ventricle placed on the right) or an anterior aorta placed to the left of the pulmonary artery arising from an infundibulum placed on the left (anatomically right ventricle placed on the left) is the specific picture of concordant transposition of the great arteries...", "contents": "Rules for diagnosis of arterioventricular discordances and spatial identification of ventricles. Crossed great arteries and transposition of the great arteries. Rules are presented for the diagnosis of arterioventricular discordances and the spatial position of the ventricles in these cardiopathies by means of angiocardiography and the position of cardiac catheters. Because these rules are based on previous anatomo-embryological findings, the normal development of the conus and the truncus is briefly analysed. The probable morphogenesis of this group of truncoconal cardiopathies is discussed. The fundamental process required to establish the diagnosis of these cardiopathies is as follows: 1) The truncoconal morphology is identified in the lateral projection. a) The anterior position of the pulmonary artery and its infundibulum with respect to the aorta and its infundibulum is characteristic of crossed great arteries with arterioventricular concordance or discordance. b) The anterior position of the aorta and its infundibulum with respect to the pulmonary artery and its infundibulum is characteristic of transposition of the great arteries with arterioventricular concordance or discordance. 2) Once the truncoconal morphology is identified, the use of the anteroposterior projection allows the establishment of the differential diagnosis between arterioventricular concordances and discordances, and of the spatial location of the ventricles in these entities. a) An anterior pulmonary artery directed from right to left, emerging from an infundibulum placed on the left side (anatomically right ventricle on the left) or an anterior pulmonary artery directed from left to right, arising from an infundibulum located to the right (anatomically right ventricular placed on the right), is the specific image of discordant crossed great arteries. b) An anterior pulmonary artery directed from right to left emerging from an infundibulum placed on the right side (anatomically right ventricle on the right side) or the anterior pulmonary artery directed from left to right arising from a left-sided infundibulum (anatomically right ventricle placed on the left side) is characteristic of concordant crossed great arteries. c) An anterior aorta placed to the right of the pulmonary artery and emerging from a left-sided infundibulum (anatomically right ventricle placed on the left side) or an anterior aorta placed to the left of the pulmonary artery and arising from an infundibulum placed on the right side (anatomically right ventricle placed on the right) is characteristic of discordant transposition of the great arteries. d) An anterior aorta placed to the right of the pulmonary artery emerging from a right-sided infundibulum (anatomically right ventricle placed on the right) or an anterior aorta placed to the left of the pulmonary artery arising from an infundibulum placed on the left (anatomically right ventricle placed on the left) is the specific picture of concordant transposition of the great arteries..."} {"id": "PMID:1267980", "title": "Catheter mapping of retrograde atrial activation. Observations during ventricular pacing and AV nodal re-entrant paroxysmal tachycardia.", "content": "A systematic study of retrograde atrial sequence at commonly used electrode catheter recording sites in 8 patients without, and in 4 patients with AV nodal re-entrant paroxysmal tachycardia was made. During right ventricular pacing, the retrograde atrial activation sequence was low septal right atrium--proximal coronary sinus--distal coronary sinus--high right atrium. During the episodes of paroxysmal tachycardia, a similar pattern was observed. This information should be helpful in the understanding of abnormal activation sequences in patients with paroxysmal supraventricular tachycardia in whom retrogradely conducting anomalous pathways are suspected.", "contents": "Catheter mapping of retrograde atrial activation. Observations during ventricular pacing and AV nodal re-entrant paroxysmal tachycardia. A systematic study of retrograde atrial sequence at commonly used electrode catheter recording sites in 8 patients without, and in 4 patients with AV nodal re-entrant paroxysmal tachycardia was made. During right ventricular pacing, the retrograde atrial activation sequence was low septal right atrium--proximal coronary sinus--distal coronary sinus--high right atrium. During the episodes of paroxysmal tachycardia, a similar pattern was observed. This information should be helpful in the understanding of abnormal activation sequences in patients with paroxysmal supraventricular tachycardia in whom retrogradely conducting anomalous pathways are suspected."} {"id": "PMID:1267981", "title": "Effects of pacing site on QRS morphology in Wolff-Parkinson-White syndrome, with special reference to 'pseudo-tachycardia-dependent block in accessory pathway and 'atrial gap'.", "content": "In a patient with a Wolff-Parkinson-White (WPW) syndrome type A mid-right atrial stimulation at a rate of 73/min produced a lesser degree of ventricular pre-excitation than when a slower sinus rhythm was present. This paradoxical effect was not related to tachycardia-dependent block in the accessory pathway because pre-excitation again increased at faster pacing rates. It was partly the result of a (proportionally) greater prolongation of intra-atrial conduction time to the accessory pathway than to the atrioventricular node and partly of a faster atrioventricular nodal conduction time. The latter, in turn, could be attributed either to later-than-normal arrival of excitation at the atrioventricular node, at a time when this structure was more recovered, or to a change in the site or mode of entry into the atrioventricular node. A gap in the atria was present because at a St1-St2 interval shorter than that which A2 had been blocked in the accessory pathway conduction was again possible, but with longer A1-A2 intervals. Finally, at similar, short, coupling intervals the impulse penetrated the atrioventricular node from the mid-right atrium but not from the coronary sinus. The unusual findings in this case support a recent assumption that in patients with WPW type A atrial stimulation should be performed from the coronary sinus to minimize the potential sources of error which can be produced by intra-atrial delay.", "contents": "Effects of pacing site on QRS morphology in Wolff-Parkinson-White syndrome, with special reference to 'pseudo-tachycardia-dependent block in accessory pathway and 'atrial gap'. In a patient with a Wolff-Parkinson-White (WPW) syndrome type A mid-right atrial stimulation at a rate of 73/min produced a lesser degree of ventricular pre-excitation than when a slower sinus rhythm was present. This paradoxical effect was not related to tachycardia-dependent block in the accessory pathway because pre-excitation again increased at faster pacing rates. It was partly the result of a (proportionally) greater prolongation of intra-atrial conduction time to the accessory pathway than to the atrioventricular node and partly of a faster atrioventricular nodal conduction time. The latter, in turn, could be attributed either to later-than-normal arrival of excitation at the atrioventricular node, at a time when this structure was more recovered, or to a change in the site or mode of entry into the atrioventricular node. A gap in the atria was present because at a St1-St2 interval shorter than that which A2 had been blocked in the accessory pathway conduction was again possible, but with longer A1-A2 intervals. Finally, at similar, short, coupling intervals the impulse penetrated the atrioventricular node from the mid-right atrium but not from the coronary sinus. The unusual findings in this case support a recent assumption that in patients with WPW type A atrial stimulation should be performed from the coronary sinus to minimize the potential sources of error which can be produced by intra-atrial delay."} {"id": "PMID:1267982", "title": "Coarctation of the aorta in infancy and childhood.", "content": "The management and results of treatment in 181 children with coarctation of the aorta are presented. In this series, 79% of the patients presented in the first year of life and 55% presented as neonates. One hundred and fifty patients were operated on, with a total surgical mortality of 21%. Only one surgical death occurred in those operated on after 3 months of age. The higher mortality in young infants is closely related to associated cardiac anomalies and to the frequency of aortic and isthmal hypoplasia. Our findings suggest that neonates presenting with heart failure and coarctation should be operated on early, as the surgical mortality under 6 weeks is 45%, whereas there is an 86% mortality in neonates who were not operated on. Analysis of follow-up indicates that when operation can be performed electively the optimal period for sugical treatment is between 6 months and 1 year of age. If operation is performed after this age, there may be persistent systemic hypertension despite relief of aortic obstruction.", "contents": "Coarctation of the aorta in infancy and childhood. The management and results of treatment in 181 children with coarctation of the aorta are presented. In this series, 79% of the patients presented in the first year of life and 55% presented as neonates. One hundred and fifty patients were operated on, with a total surgical mortality of 21%. Only one surgical death occurred in those operated on after 3 months of age. The higher mortality in young infants is closely related to associated cardiac anomalies and to the frequency of aortic and isthmal hypoplasia. Our findings suggest that neonates presenting with heart failure and coarctation should be operated on early, as the surgical mortality under 6 weeks is 45%, whereas there is an 86% mortality in neonates who were not operated on. Analysis of follow-up indicates that when operation can be performed electively the optimal period for sugical treatment is between 6 months and 1 year of age. If operation is performed after this age, there may be persistent systemic hypertension despite relief of aortic obstruction."} {"id": "PMID:1267983", "title": "Comparison of single and biplane ejection fractions in patients with Ischaemic heart disease.", "content": "Simultaneous biplane left ventriculography was performed in 59 patients with ischaemic heart disease. A comparison was made of the frontal (EFF), lateral (EFL), and biplane (EFB) ejection fractions. Discrepancies between the three measurements in the same patient were frequent observed. The patients were then grouped according to the presence or absence of signs of transmural myocardial infarction in the electrocardiogram or wall motion abnormalities, and the single and biplane EF data were again compared. There were 31 patients with previous transmural myocardial infarction and 37 patients with wall motion abnormalities, usually involving the anterior or inferior walls. The EFL of patients with transmural myocardial infarction or wall motion abnormalities commonly exceeded the EEF, because of frequent preservation of dorsal wall contraction visualized only in the lateral plane. Consequently, there was a significant difference between EFF or EFL and EFB for these patients. In contrast, there was close agreement EEF and EFL for patients without transmural myocardial infarction or wall motion abnormalities. It is concluded that differences frequently occur between single and biplane EF in patients with ischaemic heart disease, especially if transmural myocardial infarction or wall motion abnormalities are present. Hence, accurate assessment of left ventricular performance is greatly facilitated by simultaneous or sequential biplane ventriculography.", "contents": "Comparison of single and biplane ejection fractions in patients with Ischaemic heart disease. Simultaneous biplane left ventriculography was performed in 59 patients with ischaemic heart disease. A comparison was made of the frontal (EFF), lateral (EFL), and biplane (EFB) ejection fractions. Discrepancies between the three measurements in the same patient were frequent observed. The patients were then grouped according to the presence or absence of signs of transmural myocardial infarction in the electrocardiogram or wall motion abnormalities, and the single and biplane EF data were again compared. There were 31 patients with previous transmural myocardial infarction and 37 patients with wall motion abnormalities, usually involving the anterior or inferior walls. The EFL of patients with transmural myocardial infarction or wall motion abnormalities commonly exceeded the EEF, because of frequent preservation of dorsal wall contraction visualized only in the lateral plane. Consequently, there was a significant difference between EFF or EFL and EFB for these patients. In contrast, there was close agreement EEF and EFL for patients without transmural myocardial infarction or wall motion abnormalities. It is concluded that differences frequently occur between single and biplane EF in patients with ischaemic heart disease, especially if transmural myocardial infarction or wall motion abnormalities are present. Hence, accurate assessment of left ventricular performance is greatly facilitated by simultaneous or sequential biplane ventriculography."} {"id": "PMID:1267984", "title": "Vigorous exercise in leisure time, coronary risk-factors, and resting electrocardiogram in middle-aged male civil servants.", "content": "During 1968 to 1970, approximately 17 000 middle-aged male executive grade civil service officers, all of them engaged in sedentary or very light work, recorded on a Monday morning their leisure time activities over the previous Friday and Saturday. In 1971 a sample of 509 of these men completed further questionnaires for medical, social, and smoking history; these men had a resting electrocardiogram, and height, weight, skinfold thickness, blood pressure, and plasma total cholesterol were measured. Vigorous exercise in leisure time had previously been reported by 125 (25%) of the men, and these as a group had significantly fewer electrocardiographic abnormalities (changes compatible with myocardial ischaemia, ectopic beats, and sinus tachycardia) than the men not reporting vigorous exercise (P less than 0-02). This difference remained when all men with any history suggestive of cardiovascular disease were excluded from the analysis. Blood pressure, plasma total cholesterol, and smoking habits were examined with respect both to vigorous exercise and to the electrocardiogram, but the only relation found was that electrocardiographic abnormality increased with increasing blood pressure. Even among men with higher pressures, however, those reporting vigorous exercise had fewer electrographic abnormalities than the others. The results provide further support for the association of habitual physical activity with coronary health.", "contents": "Vigorous exercise in leisure time, coronary risk-factors, and resting electrocardiogram in middle-aged male civil servants. During 1968 to 1970, approximately 17 000 middle-aged male executive grade civil service officers, all of them engaged in sedentary or very light work, recorded on a Monday morning their leisure time activities over the previous Friday and Saturday. In 1971 a sample of 509 of these men completed further questionnaires for medical, social, and smoking history; these men had a resting electrocardiogram, and height, weight, skinfold thickness, blood pressure, and plasma total cholesterol were measured. Vigorous exercise in leisure time had previously been reported by 125 (25%) of the men, and these as a group had significantly fewer electrocardiographic abnormalities (changes compatible with myocardial ischaemia, ectopic beats, and sinus tachycardia) than the men not reporting vigorous exercise (P less than 0-02). This difference remained when all men with any history suggestive of cardiovascular disease were excluded from the analysis. Blood pressure, plasma total cholesterol, and smoking habits were examined with respect both to vigorous exercise and to the electrocardiogram, but the only relation found was that electrocardiographic abnormality increased with increasing blood pressure. Even among men with higher pressures, however, those reporting vigorous exercise had fewer electrographic abnormalities than the others. The results provide further support for the association of habitual physical activity with coronary health."} {"id": "PMID:1267985", "title": "Sinoatrial disease in acute myocardial infarction. Long-term prognosis.", "content": "Of 32 patients with acute myocardial infarction complicated by sinoatrial disease, 23 survived. All 23 had inferior infarction. During follow-up lasting 4 to 6 years only one patient developed severe chronic sinoatrial disease (sick sinus syndrome) necessitating permanent pacemaker treatment; twelve others died during this time. In 2 of them death was sudden 5 and 6 months after infarction. Atrial pacing studies in 7 of the 11 patients still alive showed no gross abnormalities. A review of 71 patients with chronic sinoatrial disease treated with a permanent pacemaker revealed only 5 with previous documented infarction. The present data suggest that sinus node dysfunction in patients surviving acute infarction is most often only temporary as is atrioventricular block. Occasionally, however, severe chronic sinoatrial disease requiring a permanent pacemaker may develop later, and this course of events is most likely to occur in those patients who had additional complications during the acute infarct.", "contents": "Sinoatrial disease in acute myocardial infarction. Long-term prognosis. Of 32 patients with acute myocardial infarction complicated by sinoatrial disease, 23 survived. All 23 had inferior infarction. During follow-up lasting 4 to 6 years only one patient developed severe chronic sinoatrial disease (sick sinus syndrome) necessitating permanent pacemaker treatment; twelve others died during this time. In 2 of them death was sudden 5 and 6 months after infarction. Atrial pacing studies in 7 of the 11 patients still alive showed no gross abnormalities. A review of 71 patients with chronic sinoatrial disease treated with a permanent pacemaker revealed only 5 with previous documented infarction. The present data suggest that sinus node dysfunction in patients surviving acute infarction is most often only temporary as is atrioventricular block. Occasionally, however, severe chronic sinoatrial disease requiring a permanent pacemaker may develop later, and this course of events is most likely to occur in those patients who had additional complications during the acute infarct."} {"id": "PMID:1267986", "title": "Successful electrical pacing for complete heart block complicating diphtheritic myocarditis.", "content": "A case of severe diphtheria complicated by myocarditis and neurorespiratory paralysis is reported. The myocarditis manifested with severe conduction disturbances including left bundle-branch block and high grade second degree atrioventricular block leading to Adams-Stokes attacks. Temporary transvenous electrical pacing for.3 days was successful in the management of this complication, but positive pressure ventilation was later required for respiratory paralysis. This case illustrates the potential value of electrical pacing in diphtheritic myocarditis. Sporadic cases of diphtheria still occur and the case fatality ratio remains at 10%, much of which is related to the occurrence of myocarditis.", "contents": "Successful electrical pacing for complete heart block complicating diphtheritic myocarditis. A case of severe diphtheria complicated by myocarditis and neurorespiratory paralysis is reported. The myocarditis manifested with severe conduction disturbances including left bundle-branch block and high grade second degree atrioventricular block leading to Adams-Stokes attacks. Temporary transvenous electrical pacing for.3 days was successful in the management of this complication, but positive pressure ventilation was later required for respiratory paralysis. This case illustrates the potential value of electrical pacing in diphtheritic myocarditis. Sporadic cases of diphtheria still occur and the case fatality ratio remains at 10%, much of which is related to the occurrence of myocarditis."} {"id": "PMID:1267987", "title": "Spontaneous variations in atrioventricular conduction in pre-excitation.", "content": "Atrial pacing in a patient with a Wolff-Parkinson-White syndrome pattern showed unusual variability in AV nodal conduction time. Changes in the AV nodal conduction time occurred predominantly at paced rates in excess of 100/min and consisted of abrupt or gradual decreases in the AH interval. Such decreases resulted in unexpected normalization of the QRS pattern. In addition, pacing also revealed evidence of block in the accessory pathway. Such changes in atrioventricular conduction may account for the known variability of the QRS pattern in patients with the WPW syndrome. Further, they may also explain the benign clinical course in this patient.", "contents": "Spontaneous variations in atrioventricular conduction in pre-excitation. Atrial pacing in a patient with a Wolff-Parkinson-White syndrome pattern showed unusual variability in AV nodal conduction time. Changes in the AV nodal conduction time occurred predominantly at paced rates in excess of 100/min and consisted of abrupt or gradual decreases in the AH interval. Such decreases resulted in unexpected normalization of the QRS pattern. In addition, pacing also revealed evidence of block in the accessory pathway. Such changes in atrioventricular conduction may account for the known variability of the QRS pattern in patients with the WPW syndrome. Further, they may also explain the benign clinical course in this patient."} {"id": "PMID:1267988", "title": "Transcutaneous aortovelography. A quantitative evaluation.", "content": "The haemotachograph is a non-invasive ultrasonic Doppler-shift instrument designed to measure the velocity of blood in the arch of the aorta by a technique referred to as transcutaneous aortovelography. Its accuracy has been assessed at cardiac catheterization in 20 patients. When transcutaneous aortovelographic values were compared with stroke volume determined by standard invasive techniques, a good proportional agreement was found. The accuracy of absolute flow values, as calculated from transcutaneous aortovelography and dimensional data, was, however, poor. Peak velocity determined from transcutaneous aortovelographic tracings agreed well with values obtained with a catheter tip electromagnetic velocity probe. Transcutaneous aortovelography is a useful non-invasive technique which can be used to determine phasic blood flow velocity in the aortic arch and to follow changes in cardiac output over a period of time.", "contents": "Transcutaneous aortovelography. A quantitative evaluation. The haemotachograph is a non-invasive ultrasonic Doppler-shift instrument designed to measure the velocity of blood in the arch of the aorta by a technique referred to as transcutaneous aortovelography. Its accuracy has been assessed at cardiac catheterization in 20 patients. When transcutaneous aortovelographic values were compared with stroke volume determined by standard invasive techniques, a good proportional agreement was found. The accuracy of absolute flow values, as calculated from transcutaneous aortovelography and dimensional data, was, however, poor. Peak velocity determined from transcutaneous aortovelographic tracings agreed well with values obtained with a catheter tip electromagnetic velocity probe. Transcutaneous aortovelography is a useful non-invasive technique which can be used to determine phasic blood flow velocity in the aortic arch and to follow changes in cardiac output over a period of time."} {"id": "PMID:1267989", "title": "Transcutaneous aortovelography. Potentially useful technique in management of critically ill patients.", "content": "Pilot evaluation of the clinical use of transcutaneous aortovelography has been undertaken and suggests that this technique will be useful in the assessment of left ventricular function in the acutely ill patient. Changes in waveform as a result of therapy or alteration in clinical condition can frequently be noted by critical visual assessment. Increasing clinical experience suggests that quantification will permit interpretation of less obvious changes in the recorded waveform. Transcutaneous aortovelography has the simplicity, speed, and safety afforded by a non-invasive technique.", "contents": "Transcutaneous aortovelography. Potentially useful technique in management of critically ill patients. Pilot evaluation of the clinical use of transcutaneous aortovelography has been undertaken and suggests that this technique will be useful in the assessment of left ventricular function in the acutely ill patient. Changes in waveform as a result of therapy or alteration in clinical condition can frequently be noted by critical visual assessment. Increasing clinical experience suggests that quantification will permit interpretation of less obvious changes in the recorded waveform. Transcutaneous aortovelography has the simplicity, speed, and safety afforded by a non-invasive technique."} {"id": "PMID:1267990", "title": "Incidence of arrhythmias induced by isometric and dynamic exercise.", "content": "The incidence of arrhythmias during isometric sustained handgrip exercise and during dynamic graded bicycle exercise was compared in a group of 45 patients with various forms of heart disease on no antiarrhythmic therapy. Atrial arrhythmias were equally common during handgrip and bicycle exercise but ventricular arrhythmias were more frequent during handgrip exercise. Of the 45 patients, 38 per cent developed ventricular arrhythmias during isometric exercise, with ventricular tachycardia occurring in 15 per cent. During dynamic exercise 22 per cent of the 45 patients developed ventricular arrhythmias, with ventricular tachycardia occurring in 2 per cent. Patients with coronary artery disease and/or depressed left ventricular function developed twice the incidence of ventricular arrhythmias with isometric than with dynamic exercise. Thus, isometric exercise testing is of more value than dynamic exercise testing in unmasking latent ventricular arrhythmias in patients with heart disease.", "contents": "Incidence of arrhythmias induced by isometric and dynamic exercise. The incidence of arrhythmias during isometric sustained handgrip exercise and during dynamic graded bicycle exercise was compared in a group of 45 patients with various forms of heart disease on no antiarrhythmic therapy. Atrial arrhythmias were equally common during handgrip and bicycle exercise but ventricular arrhythmias were more frequent during handgrip exercise. Of the 45 patients, 38 per cent developed ventricular arrhythmias during isometric exercise, with ventricular tachycardia occurring in 15 per cent. During dynamic exercise 22 per cent of the 45 patients developed ventricular arrhythmias, with ventricular tachycardia occurring in 2 per cent. Patients with coronary artery disease and/or depressed left ventricular function developed twice the incidence of ventricular arrhythmias with isometric than with dynamic exercise. Thus, isometric exercise testing is of more value than dynamic exercise testing in unmasking latent ventricular arrhythmias in patients with heart disease."} {"id": "PMID:1267991", "title": "Interaction between cardiovascular responses to sustained handgrip and Valsalva manoeuvre.", "content": "Interactions between the cardiovascular responses to the Valsalva manoeuvre and sustained handgrip were analysed in 5 men with untreated mild hypertension and 4 young normal subjects. Though set at a higher level, there was a normal blood pressure response to the Valsalva manoeuvre during concurrent sustained handgrip in 4 of the 5 hypertensive subjects. At the end of the handgrip period in which the Valsalva manoeuvres were performed, the blood pressure was higher and the heart rate lower than in the control period of sustained handgrip. The fifth subject developed a 'square wave' Valsalva response, which returned to a normal response when sustained handgrip was discontinued. Analysis of RR interval changes in the normal subjects showed that both the tachycardia during, and the bradycardia after, the Valsalva strain period were significantly reduced during simultaneous sustained handgrip. These results show that the two reflexes interact, but only to a minor extent, and that the baroreflex response is modified by sustained handgrip, rather than overridden as had previously been suggested. In view of the effect on the blood pressure and heart rate, subjects should avoid performing a Valsalva manoeuvre during sustained handgrip testing.", "contents": "Interaction between cardiovascular responses to sustained handgrip and Valsalva manoeuvre. Interactions between the cardiovascular responses to the Valsalva manoeuvre and sustained handgrip were analysed in 5 men with untreated mild hypertension and 4 young normal subjects. Though set at a higher level, there was a normal blood pressure response to the Valsalva manoeuvre during concurrent sustained handgrip in 4 of the 5 hypertensive subjects. At the end of the handgrip period in which the Valsalva manoeuvres were performed, the blood pressure was higher and the heart rate lower than in the control period of sustained handgrip. The fifth subject developed a 'square wave' Valsalva response, which returned to a normal response when sustained handgrip was discontinued. Analysis of RR interval changes in the normal subjects showed that both the tachycardia during, and the bradycardia after, the Valsalva strain period were significantly reduced during simultaneous sustained handgrip. These results show that the two reflexes interact, but only to a minor extent, and that the baroreflex response is modified by sustained handgrip, rather than overridden as had previously been suggested. In view of the effect on the blood pressure and heart rate, subjects should avoid performing a Valsalva manoeuvre during sustained handgrip testing."} {"id": "PMID:1267992", "title": "Left ventricular function after aortic valve replacement.", "content": "Changes in haemodynamics and in systolic time intervals, early after valve replacement, were studied in a group of 15 patients. Though all the haemodynamic measurements were within normal limits at 44 hours after operation, there was a persistent change in systolic time intervals (shortening of left ventricular ejection time and electromechanical systole, and prolongation of pre-ejection period and increase in the ratio PEP/LVET). The effect of periods of myocardial ischaemia during cardiopulmonary bypass on myocardial function is suggested as the explanation for the changes observed.", "contents": "Left ventricular function after aortic valve replacement. Changes in haemodynamics and in systolic time intervals, early after valve replacement, were studied in a group of 15 patients. Though all the haemodynamic measurements were within normal limits at 44 hours after operation, there was a persistent change in systolic time intervals (shortening of left ventricular ejection time and electromechanical systole, and prolongation of pre-ejection period and increase in the ratio PEP/LVET). The effect of periods of myocardial ischaemia during cardiopulmonary bypass on myocardial function is suggested as the explanation for the changes observed."} {"id": "PMID:1267993", "title": "Anomalous iliac compliance in children with a single umbilical artery.", "content": "Arterial compliance (C) has been measured in 18 children known to have had a single umbilical artery at birth. Non-invasive ultrasonic Doppler techniques were used to measure C for the aorta, iliac, and leg arteries. Anomalous compliance was found between the two iliac vessels, and it is suggested that this is the result of haemodynamic stress-induced changes during development. The demonstration that the form of large arteries may be changed by altered haemodynamic stress and that their physiological function is thus affected, may have important implications in the pathogenesis of degenerative disease.", "contents": "Anomalous iliac compliance in children with a single umbilical artery. Arterial compliance (C) has been measured in 18 children known to have had a single umbilical artery at birth. Non-invasive ultrasonic Doppler techniques were used to measure C for the aorta, iliac, and leg arteries. Anomalous compliance was found between the two iliac vessels, and it is suggested that this is the result of haemodynamic stress-induced changes during development. The demonstration that the form of large arteries may be changed by altered haemodynamic stress and that their physiological function is thus affected, may have important implications in the pathogenesis of degenerative disease."} {"id": "PMID:1268024", "title": "Relationship between antigenicity and morphology of murine lung adenomata.", "content": "Thirty-six lung adenomata induced in mice by urethane followed or not by cortisone, all had an adenomatous morphology at first s.c. transplant in syngeneic hosts. Seventeen of them acquired a sarcomatous structure within a few s.c. transplant generations whilst the other 19 remained adenomatous for as long as tested, i.e. at least 10 transplant generations. The change of morphology was not dependent on s.c. growth, since tumours also transformed when allowed to grow in the lung, and was not correlated to the capacity of a tumour for growth or metastasis. The 2 types of tumours were antigenically different, since only tumours that after few transplants changed their morphology were found at the first s.c. transplant to possess tumour-associated membrane antigens as revealed by an in vitro test. In addition, only the tumours which acquired a sarcomatous morphology were found gs-positive. The majority of antigenic primary tumours arose in mice belonging to the groups of treatment which induced the strongest immunodepression. It is suggested that a predisposition to sarcoma progression is related to an immunological control, at the time of adenoma induction, of an oncornavirus, responsible for the superimposed sarcomatous change.", "contents": "Relationship between antigenicity and morphology of murine lung adenomata. Thirty-six lung adenomata induced in mice by urethane followed or not by cortisone, all had an adenomatous morphology at first s.c. transplant in syngeneic hosts. Seventeen of them acquired a sarcomatous structure within a few s.c. transplant generations whilst the other 19 remained adenomatous for as long as tested, i.e. at least 10 transplant generations. The change of morphology was not dependent on s.c. growth, since tumours also transformed when allowed to grow in the lung, and was not correlated to the capacity of a tumour for growth or metastasis. The 2 types of tumours were antigenically different, since only tumours that after few transplants changed their morphology were found at the first s.c. transplant to possess tumour-associated membrane antigens as revealed by an in vitro test. In addition, only the tumours which acquired a sarcomatous morphology were found gs-positive. The majority of antigenic primary tumours arose in mice belonging to the groups of treatment which induced the strongest immunodepression. It is suggested that a predisposition to sarcoma progression is related to an immunological control, at the time of adenoma induction, of an oncornavirus, responsible for the superimposed sarcomatous change."} {"id": "PMID:1268028", "title": "Carcinoembryonic antigen: isolation of a sub-fraction with high specific activity.", "content": "Four sub-fractions of carcinoembryonic antigen have been obtained by chromatography of conventional CEA on Con A-Sepharose and their immunoreactive contents have been determined. Comparative studies have shown that a fraction eluted with 2% methyl glucoside (CEA 2B) had the highest activity, with a potency (60 u/mug) twice that of unfractionated CEA although appreciable activity was also found in the other fractions. The amino acid composition of CEA 2B is similar to that reported for conventional CEA but there is a lower content of neutral hexoses and a comparatively high content of N-acetylglucosamine. Experiments with a pool of sera from 11 patients with colonic cancer, which had been fractionated on Con A-Sepharose, have shown that nearly all the CEA activity was contained in a fraction eluted with 2% methyl glucoside. A convenient method of isolating CEA with high specific activity directly from perchloric acid extracts of tumour tissue is also described.", "contents": "Carcinoembryonic antigen: isolation of a sub-fraction with high specific activity. Four sub-fractions of carcinoembryonic antigen have been obtained by chromatography of conventional CEA on Con A-Sepharose and their immunoreactive contents have been determined. Comparative studies have shown that a fraction eluted with 2% methyl glucoside (CEA 2B) had the highest activity, with a potency (60 u/mug) twice that of unfractionated CEA although appreciable activity was also found in the other fractions. The amino acid composition of CEA 2B is similar to that reported for conventional CEA but there is a lower content of neutral hexoses and a comparatively high content of N-acetylglucosamine. Experiments with a pool of sera from 11 patients with colonic cancer, which had been fractionated on Con A-Sepharose, have shown that nearly all the CEA activity was contained in a fraction eluted with 2% methyl glucoside. A convenient method of isolating CEA with high specific activity directly from perchloric acid extracts of tumour tissue is also described."} {"id": "PMID:1268029", "title": "Influence of leukaemic cells on the colony formation of human bone marrow cells in vitro II. Suppressive effects of leukaemic cell extracts.", "content": "The influence of leukaemic cells on the colony formation of human bone marrow cells was studied in vitro as an extension of our previous work (Chiyoda et al., 1975). An extract of leukaemic bone marrow cells significantly suppressed colony forming ability of the normal bone marrow cells, whereas an extract of normal bone marrow cells did not suppress it except in two cases. The suppressive effect of normal bone marrow cells, however, was obviously less intense than that of leukaemic cells. This suppressive effect was dose dependent and was fairly stable to heat treatment. These results suggest that leukaemic bone marrow cells contain factor(s) which suppress normal colony formation.", "contents": "Influence of leukaemic cells on the colony formation of human bone marrow cells in vitro II. Suppressive effects of leukaemic cell extracts. The influence of leukaemic cells on the colony formation of human bone marrow cells was studied in vitro as an extension of our previous work (Chiyoda et al., 1975). An extract of leukaemic bone marrow cells significantly suppressed colony forming ability of the normal bone marrow cells, whereas an extract of normal bone marrow cells did not suppress it except in two cases. The suppressive effect of normal bone marrow cells, however, was obviously less intense than that of leukaemic cells. This suppressive effect was dose dependent and was fairly stable to heat treatment. These results suggest that leukaemic bone marrow cells contain factor(s) which suppress normal colony formation."} {"id": "PMID:1268030", "title": "Antitumour activity of adenovirus-12 structural proteins against Moloney sarcoma tumours in mice.", "content": "When purified fibre and hexon proteins of adenovirus 12 were given intramuscularly to 4-week-old BALB/c mice (250-300 mug/mouse) 2 h prior to inoculation with mouse sarcoma virus (0.05 ml of 10(4) FFU/ml) at the same site, significant suppression of tumour growth (P less than 0.001), and rapid regression in tumour size (P less than 0.001) were noted. As a rule, the survival rate in treated mice was also significantly higher than in untreated mice. Furthermore, the disease process in treated mice as compared to untreated mice was far less extensive as judged by the scarcity of sarcoma lesions on the spleens. Preliminary evidence suggested that treatment with fibre could lead to increased cellular immunity in mice. Whether this may be a secondary consequence of events whereby fibre inhibited tumour growth rather than first order mechanism of the inhibition is not known.", "contents": "Antitumour activity of adenovirus-12 structural proteins against Moloney sarcoma tumours in mice. When purified fibre and hexon proteins of adenovirus 12 were given intramuscularly to 4-week-old BALB/c mice (250-300 mug/mouse) 2 h prior to inoculation with mouse sarcoma virus (0.05 ml of 10(4) FFU/ml) at the same site, significant suppression of tumour growth (P less than 0.001), and rapid regression in tumour size (P less than 0.001) were noted. As a rule, the survival rate in treated mice was also significantly higher than in untreated mice. Furthermore, the disease process in treated mice as compared to untreated mice was far less extensive as judged by the scarcity of sarcoma lesions on the spleens. Preliminary evidence suggested that treatment with fibre could lead to increased cellular immunity in mice. Whether this may be a secondary consequence of events whereby fibre inhibited tumour growth rather than first order mechanism of the inhibition is not known."} {"id": "PMID:1268031", "title": "Stimulation of cellular ingestion by basic proteins in vitro.", "content": "The ingestion of carbon and benzpyrene particles in vitro by rat peritoneal macrophages, baby hamster kidney fibroblasts (BHK-21) and mouse L-cells has been shown to be significantly stimulated by the inclusion of histone or polylysine in the culture medium. Parallel studies using methylated bovine albumin did not significantly stimulate carbon or benzpyrene uptake relative to untreated control cultures. Incubation of carbon particles with histone before inclusion in the culture medium of macrophages resulted in the same degree of uptake as in the cultures where carbon and histone were added independently of each other. The implications of these findings to in vivo chemical carcinogenesis are examined.", "contents": "Stimulation of cellular ingestion by basic proteins in vitro. The ingestion of carbon and benzpyrene particles in vitro by rat peritoneal macrophages, baby hamster kidney fibroblasts (BHK-21) and mouse L-cells has been shown to be significantly stimulated by the inclusion of histone or polylysine in the culture medium. Parallel studies using methylated bovine albumin did not significantly stimulate carbon or benzpyrene uptake relative to untreated control cultures. Incubation of carbon particles with histone before inclusion in the culture medium of macrophages resulted in the same degree of uptake as in the cultures where carbon and histone were added independently of each other. The implications of these findings to in vivo chemical carcinogenesis are examined."} {"id": "PMID:1268032", "title": "Carcinogenic effects of different nitroso-compounds in Chinese hamsters. I. Dimethylnitrosamine and N-diethylnitrosamine.", "content": "Three hundred and twenty Chinese hamsters (Cricetulus griseus) (CH) were treated (s.c.) with 1/5, 1/10 or 1/20 LD50 of dimethylnitrosamine (DMN) or N-diethylnitrosamine (DEN). These substances, in several respects, showed a different organotropy in this species than in both the Syrian golden (SGH) and the European hamster (EH). In CH, DEN produced up to 100% squamous cell papillomata and occasionally also carcinomata of the cheek pouch, tongue, pharynix, oesophagus and forestomach. With DEN a high rate of hepatomata was simultaneously realized. DMN induced a considerable quantity of liver tumours, the highest incidence being demonstrated in the lowest dosage group.", "contents": "Carcinogenic effects of different nitroso-compounds in Chinese hamsters. I. Dimethylnitrosamine and N-diethylnitrosamine. Three hundred and twenty Chinese hamsters (Cricetulus griseus) (CH) were treated (s.c.) with 1/5, 1/10 or 1/20 LD50 of dimethylnitrosamine (DMN) or N-diethylnitrosamine (DEN). These substances, in several respects, showed a different organotropy in this species than in both the Syrian golden (SGH) and the European hamster (EH). In CH, DEN produced up to 100% squamous cell papillomata and occasionally also carcinomata of the cheek pouch, tongue, pharynix, oesophagus and forestomach. With DEN a high rate of hepatomata was simultaneously realized. DMN induced a considerable quantity of liver tumours, the highest incidence being demonstrated in the lowest dosage group."} {"id": "PMID:1268033", "title": "The roles of age at treatment and dose in carcinogenesis in C3Hf/Dp mice with a single administration of N-nitroso-N-methylurea.", "content": "C3Hf/Dp mice were given a single i.p. injection of 50, 25 or 5 mug/g N-Nitroso-N-Methylurea (NMU) at either 1 or 70 days of age or 50 mug/g at 21 days of age. They were observed until death or until 120 weeks of age. The two highest doses of NMU produced tumours in a wide spectrum of organs, including the thymus, forestomach, lung, liver (only in males), kidneys, ovaries and orbital glands. The only two tumour types which appeared to be closely related to the occurrence of death were thymic lymphomata (most of which were found in mice dying before 40 weeks after treatment) and carcinomata of the forestomach. Lifetime analyses are presented concerning the occurrence of these two tumour types as well as the occurrence of any tumour after 40 weeks of age or since treatment. Incidences of thymic lymphomata were 67.6%, 39.0% and 21.2% in mice receiving 50 mug/g NMU at 1, 21 and 70 days respectively and 17.1% in mice receiving 25 mug/g at 1 day. In the other groups the incidence of thymic lymphomata was zero or negligible. The rate of progression of thymic lymphomata until death was related to both earliness of treatment and dose. On the contrary, incidences and progression of carcinomata of the forestomach were unrelated to age at treatment. Since breakdown of NMU is very rapid and does not require enzymes, these results are considered as evidence that host-tumour interaction differs from organ to organ. No excess of tumours over the controls was found in mice receiving 5 mug/g either at 1 or 70 days of age.", "contents": "The roles of age at treatment and dose in carcinogenesis in C3Hf/Dp mice with a single administration of N-nitroso-N-methylurea. C3Hf/Dp mice were given a single i.p. injection of 50, 25 or 5 mug/g N-Nitroso-N-Methylurea (NMU) at either 1 or 70 days of age or 50 mug/g at 21 days of age. They were observed until death or until 120 weeks of age. The two highest doses of NMU produced tumours in a wide spectrum of organs, including the thymus, forestomach, lung, liver (only in males), kidneys, ovaries and orbital glands. The only two tumour types which appeared to be closely related to the occurrence of death were thymic lymphomata (most of which were found in mice dying before 40 weeks after treatment) and carcinomata of the forestomach. Lifetime analyses are presented concerning the occurrence of these two tumour types as well as the occurrence of any tumour after 40 weeks of age or since treatment. Incidences of thymic lymphomata were 67.6%, 39.0% and 21.2% in mice receiving 50 mug/g NMU at 1, 21 and 70 days respectively and 17.1% in mice receiving 25 mug/g at 1 day. In the other groups the incidence of thymic lymphomata was zero or negligible. The rate of progression of thymic lymphomata until death was related to both earliness of treatment and dose. On the contrary, incidences and progression of carcinomata of the forestomach were unrelated to age at treatment. Since breakdown of NMU is very rapid and does not require enzymes, these results are considered as evidence that host-tumour interaction differs from organ to organ. No excess of tumours over the controls was found in mice receiving 5 mug/g either at 1 or 70 days of age."} {"id": "PMID:1268034", "title": "The results of diethylstilboestrol therapy for recurrent and metastatic carcinoma of the male breast.", "content": "A retrospective survey has been made of 58 patients with recurrent and advanced male breast cancer treated with oral diethylstilboestrol. Fifty-five patients were suitable for assessment. Fourteen patients had an objective response and 7 had a partial response giving a total response of 21/55 patients (38%). The median remission for the objective responders was 7 years. Three patients are alive and free of disease; one has now been in remission for 13 years. It is suggested that diethylstilboestrol is a useful treatment in patients with soft tissue disease (breast, chest wall and/or lymph nodes).", "contents": "The results of diethylstilboestrol therapy for recurrent and metastatic carcinoma of the male breast. A retrospective survey has been made of 58 patients with recurrent and advanced male breast cancer treated with oral diethylstilboestrol. Fifty-five patients were suitable for assessment. Fourteen patients had an objective response and 7 had a partial response giving a total response of 21/55 patients (38%). The median remission for the objective responders was 7 years. Three patients are alive and free of disease; one has now been in remission for 13 years. It is suggested that diethylstilboestrol is a useful treatment in patients with soft tissue disease (breast, chest wall and/or lymph nodes)."} {"id": "PMID:1268037", "title": "The reversibility by dipyridamole of the increased sensitivity of in vivo platelet aggregation in rabbits after alloxan.", "content": "Rabbits hyperglycaemic after previous intravenous injection with alloxan show an increased sensitivity of the aggregation of platelets to adenosine diphosphate applied topically to injured arteries. This increased sensitivity is completely reversed by treatment with oral dipyridamole but returns if the dipyridamole is withdrawn.", "contents": "The reversibility by dipyridamole of the increased sensitivity of in vivo platelet aggregation in rabbits after alloxan. Rabbits hyperglycaemic after previous intravenous injection with alloxan show an increased sensitivity of the aggregation of platelets to adenosine diphosphate applied topically to injured arteries. This increased sensitivity is completely reversed by treatment with oral dipyridamole but returns if the dipyridamole is withdrawn."} {"id": "PMID:1268038", "title": "The hepatotoxicity of O,O-diethyl, O-phenyl phosphorothionate (SV1) for the rat.", "content": "The parathion analogue O, O-diethyl, O-phenyl phosphorothionate (SV1) is hepatotoxic when given in large intraperitoneal doses (400 mg/kg body weight) to male rats that have been treated previously with phenobarbitone. The lesion produced at 24 h after dosing is a periacinar hydropic degeneration which appears identical to that caused by carbon disulphide (CS2) in similarly pretreated rats. Both lesions are characterized by a marked depression in hepatic microsomal cytochrome P-450 levels, no change in the concentrations of Na+, K+ and Ca++ in liver water, in contrast to the periacinar necrogenic lesion caused by tccl4 in which Na+ and Ca++ levels markedly increase while that of K+ decreases. The similarity of the SV1 and CS2 induced liver changes, the fact that both chemicals undergo a similar oxidative desulphuration in the liver microsomes and that prior induction of the latter enzymes is necessary in order to produce the injury suggest a similar mechanism for both lesions. A reactive form of sulphur released from the metabolism of CS2 and phosphorothionates in the liver may become covalently bound to constituents of the endoplasmic reticulum of the liver cell and in this way initiate the toxic liver changes. Drugs and chemicals which contain P=S or C=S bonds and which undergo oxidative desulphuration in the liver could thus be similarly hepatotoxic.", "contents": "The hepatotoxicity of O,O-diethyl, O-phenyl phosphorothionate (SV1) for the rat. The parathion analogue O, O-diethyl, O-phenyl phosphorothionate (SV1) is hepatotoxic when given in large intraperitoneal doses (400 mg/kg body weight) to male rats that have been treated previously with phenobarbitone. The lesion produced at 24 h after dosing is a periacinar hydropic degeneration which appears identical to that caused by carbon disulphide (CS2) in similarly pretreated rats. Both lesions are characterized by a marked depression in hepatic microsomal cytochrome P-450 levels, no change in the concentrations of Na+, K+ and Ca++ in liver water, in contrast to the periacinar necrogenic lesion caused by tccl4 in which Na+ and Ca++ levels markedly increase while that of K+ decreases. The similarity of the SV1 and CS2 induced liver changes, the fact that both chemicals undergo a similar oxidative desulphuration in the liver microsomes and that prior induction of the latter enzymes is necessary in order to produce the injury suggest a similar mechanism for both lesions. A reactive form of sulphur released from the metabolism of CS2 and phosphorothionates in the liver may become covalently bound to constituents of the endoplasmic reticulum of the liver cell and in this way initiate the toxic liver changes. Drugs and chemicals which contain P=S or C=S bonds and which undergo oxidative desulphuration in the liver could thus be similarly hepatotoxic."} {"id": "PMID:1268039", "title": "Glomerular lesions in experimental renal papillary necrosis. I. Ultrastructural aspects and some pathogenic considerations.", "content": "Papillary necrosis was induced in rats by a single intravenous injection of bromoethylamine hydrobromide (BEA). From 7 days on glomerular lesions were recognized. They consisted of electron dense deposits mainly subepithelial in location; mild mesangial hypercellularity and matrix increase. Immunofluorescence with anti-rat gammaglobulin was positive, showing granular fluorescence in relation with basement membrane and mesangium. The possibility is raised that these lesions are due to the pathogenic action of immune complexes, the antigen being one arising during the necrosis of the renal papilla. It is also suggested that this mechanism can be operative in ths human being in cases of papillary necrosis of the kidney.", "contents": "Glomerular lesions in experimental renal papillary necrosis. I. Ultrastructural aspects and some pathogenic considerations. Papillary necrosis was induced in rats by a single intravenous injection of bromoethylamine hydrobromide (BEA). From 7 days on glomerular lesions were recognized. They consisted of electron dense deposits mainly subepithelial in location; mild mesangial hypercellularity and matrix increase. Immunofluorescence with anti-rat gammaglobulin was positive, showing granular fluorescence in relation with basement membrane and mesangium. The possibility is raised that these lesions are due to the pathogenic action of immune complexes, the antigen being one arising during the necrosis of the renal papilla. It is also suggested that this mechanism can be operative in ths human being in cases of papillary necrosis of the kidney."} {"id": "PMID:1268040", "title": "The behaviour in ferrets of two closely related clones of influenza virus of differing virulence for man.", "content": "Clones 7a and 64d of the recombinant influenza virus A/PR/8/34-A/England/939/69(H3N2) which are of different virulence for man as judged by clinical score (7a more virulent than 64d) showed similar differences in ferrets. With intranasal inoculation the approximate 50% minimal infectious doses of both clones were similar (between 10(0) and 10(2) EID(50)) as were their titres in nasal washes 24 h after inoculation and the histologically evident damage they caused in the nasal turbinates. However, clone 7a persisted in the nasal washes more than 64d and produced a more prolonged pyrexia. Furthermore, 7a consistently produced a lung infection which was produced only occasionally by 64d and then to a lesser extent than 7a. In contrast to nasal mucosa, histological damage in the lung was slight with both strains. Differences in replication of 7a and 64d in organ cultures of nasal turbinates appeared only after 24 h incubation. They were not sufficiently large to explain the markedly superior ability of 7a to persist in the nasal tract in vivo. This persistence, which coincides with the production of pyrexia, may be due to a greater ability of 7a to resist induced systemic host defences. Spasmodic isolations of infective virus of both clones were made from extra-respiratory tissues such as liver, spleen and kidney.", "contents": "The behaviour in ferrets of two closely related clones of influenza virus of differing virulence for man. Clones 7a and 64d of the recombinant influenza virus A/PR/8/34-A/England/939/69(H3N2) which are of different virulence for man as judged by clinical score (7a more virulent than 64d) showed similar differences in ferrets. With intranasal inoculation the approximate 50% minimal infectious doses of both clones were similar (between 10(0) and 10(2) EID(50)) as were their titres in nasal washes 24 h after inoculation and the histologically evident damage they caused in the nasal turbinates. However, clone 7a persisted in the nasal washes more than 64d and produced a more prolonged pyrexia. Furthermore, 7a consistently produced a lung infection which was produced only occasionally by 64d and then to a lesser extent than 7a. In contrast to nasal mucosa, histological damage in the lung was slight with both strains. Differences in replication of 7a and 64d in organ cultures of nasal turbinates appeared only after 24 h incubation. They were not sufficiently large to explain the markedly superior ability of 7a to persist in the nasal tract in vivo. This persistence, which coincides with the production of pyrexia, may be due to a greater ability of 7a to resist induced systemic host defences. Spasmodic isolations of infective virus of both clones were made from extra-respiratory tissues such as liver, spleen and kidney."} {"id": "PMID:1268041", "title": "The ultrastructure of the reaction of arterial walls to cholesterol crystals in atheroembolism.", "content": "Scanning electron microscopy of atheromatous material revealed flat rhombic cholesterol crystals piled one upon the other. The fate of cholesterol crystals in the atheromatous material was followed after injection intra-arterially into the left renal arteries and left common carotid arteries of rabbits. The lipid and membranous component of the atheromatous material disappeared from the lumen of the vessels in 2-3 days after injection. Macrophages engulfed small cholesterol crystals and exposed surfaces attracted a layer of platelets. Larger cholesterol crystals evoked a giant cell response while within the lumen. Some cholesterol crystals penetrated the vessel walls or were included in the vessel wall reaction and induced a covering of endothelial cells sequestrating them from the lumen. The cholesterol crystals contained in some of the macrophages showed fracture lines and in some instances there were associated myelin figures. Large cholesterol crystals eventually elicited a fibroblastic response from the vessel wall (at about 1-4 weeks after injection) which could give rise to partial or almost complete occlusion of the vessel lumen.", "contents": "The ultrastructure of the reaction of arterial walls to cholesterol crystals in atheroembolism. Scanning electron microscopy of atheromatous material revealed flat rhombic cholesterol crystals piled one upon the other. The fate of cholesterol crystals in the atheromatous material was followed after injection intra-arterially into the left renal arteries and left common carotid arteries of rabbits. The lipid and membranous component of the atheromatous material disappeared from the lumen of the vessels in 2-3 days after injection. Macrophages engulfed small cholesterol crystals and exposed surfaces attracted a layer of platelets. Larger cholesterol crystals evoked a giant cell response while within the lumen. Some cholesterol crystals penetrated the vessel walls or were included in the vessel wall reaction and induced a covering of endothelial cells sequestrating them from the lumen. The cholesterol crystals contained in some of the macrophages showed fracture lines and in some instances there were associated myelin figures. Large cholesterol crystals eventually elicited a fibroblastic response from the vessel wall (at about 1-4 weeks after injection) which could give rise to partial or almost complete occlusion of the vessel lumen."} {"id": "PMID:1268042", "title": "Cellular proliferation in the urinary tract epithelium of the rat following temporary unilateral renal ischaemia.", "content": "A study of the effect of temporary unilateral renal ischaemia on the epithelium lining the renal pelvis and the bladder of the rat is described. There is a significant increase in the mitotic index in the pelvic epithelium of the affected kidneys, presenting a well-defined peak approximately 36 h after reflow. A similar but less pronounced cellular proliferation occurs in the bladder epithelium. The increased mitotic index in the renal pelvis and the bladder is not preceded by any detectable cell destruction at either site. It also has a different time course from the tubular regeneration which follows renal ischaemia.", "contents": "Cellular proliferation in the urinary tract epithelium of the rat following temporary unilateral renal ischaemia. A study of the effect of temporary unilateral renal ischaemia on the epithelium lining the renal pelvis and the bladder of the rat is described. There is a significant increase in the mitotic index in the pelvic epithelium of the affected kidneys, presenting a well-defined peak approximately 36 h after reflow. A similar but less pronounced cellular proliferation occurs in the bladder epithelium. The increased mitotic index in the renal pelvis and the bladder is not preceded by any detectable cell destruction at either site. It also has a different time course from the tubular regeneration which follows renal ischaemia."} {"id": "PMID:1268043", "title": "A quantitative assessment of the structural changes the rat's liver following obstruction of the common bile duct.", "content": "A study has been made of sequential changes in the rat's liver from 1 to 40 days after obstruction of the common bile duct. The qualitative changes have been described and illustrated. The volume proportions of hepatocytes, bile duct epithelium and biliary stroma have been quantified by histological analysis using a point counting technique. The proliferation of hepatocytes and bile duct cells have been measured by labelling with tritiated thymidine. The absolute quantity of hepatocytes in each liver has been estimated and expressed as a percentage of body weight. Over 40 days there is a relative fall in the volume proportion of hepatocytes and an increase in bile duct cells and biliary stroma. These changes in volume proportions are related directly to the period of jaundice. Biliary stroma increases in support of new bile duct tissue and there is no excessive fibrosis. Hepatocytes proliferate at a greater rate than normal after obstruction of the common bile duct and the degree of proliferation reaches a maximum of 24 times that of normal 4 days after obstruction. Similarly, the proliferation of bile duct epithelium is increased in obstructive jaundice but in this instance it reaches a maximum of 50 times that of normal 24 h after ligation of the common bile duct. The absolute quantity of hepatocytes in the liver probably falls during the period of jaundice. However, the fall is less than anticipated from the volume proportion of hepatocytes because of the overall increase in liver size.", "contents": "A quantitative assessment of the structural changes the rat's liver following obstruction of the common bile duct. A study has been made of sequential changes in the rat's liver from 1 to 40 days after obstruction of the common bile duct. The qualitative changes have been described and illustrated. The volume proportions of hepatocytes, bile duct epithelium and biliary stroma have been quantified by histological analysis using a point counting technique. The proliferation of hepatocytes and bile duct cells have been measured by labelling with tritiated thymidine. The absolute quantity of hepatocytes in each liver has been estimated and expressed as a percentage of body weight. Over 40 days there is a relative fall in the volume proportion of hepatocytes and an increase in bile duct cells and biliary stroma. These changes in volume proportions are related directly to the period of jaundice. Biliary stroma increases in support of new bile duct tissue and there is no excessive fibrosis. Hepatocytes proliferate at a greater rate than normal after obstruction of the common bile duct and the degree of proliferation reaches a maximum of 24 times that of normal 4 days after obstruction. Similarly, the proliferation of bile duct epithelium is increased in obstructive jaundice but in this instance it reaches a maximum of 50 times that of normal 24 h after ligation of the common bile duct. The absolute quantity of hepatocytes in the liver probably falls during the period of jaundice. However, the fall is less than anticipated from the volume proportion of hepatocytes because of the overall increase in liver size."} {"id": "PMID:1268044", "title": "Studies of the morphology and tumorigenicity of experimental brain tumours in tissue culture.", "content": "Brain tumours induced transplacentally in BD-IX rats by a single dose of N-ethyl-N-nitrosourea have been successfully grown in tissue culture. These tumours were malignant pleomorphic gliomas. The cultured cells retained their glial morphology both in vitro and on reinjection into syngeneic hosts: astrocytes became the predominant cell type. The ability of the cells to form tumours increased with time in culture as reflected both in the decreased latency of the tumours and in the increased ability of the cells to grow in semi-solid medium.", "contents": "Studies of the morphology and tumorigenicity of experimental brain tumours in tissue culture. Brain tumours induced transplacentally in BD-IX rats by a single dose of N-ethyl-N-nitrosourea have been successfully grown in tissue culture. These tumours were malignant pleomorphic gliomas. The cultured cells retained their glial morphology both in vitro and on reinjection into syngeneic hosts: astrocytes became the predominant cell type. The ability of the cells to form tumours increased with time in culture as reflected both in the decreased latency of the tumours and in the increased ability of the cells to grow in semi-solid medium."} {"id": "PMID:1268045", "title": "Factors influencing the survival of cell monolayers during storage at 4 degrees.", "content": "As a step towards the definition of a medium suitable for long-term storage of potential organ transplants, a study was made of the effects of various solutions on the viability of monolayers of cells stored at 4 degrees. It was found that, for these to survive for more than a few hours, an essential component of the medium was a non-toxic solute which did not cross the cell membrane at low temperatures and could therefore counterbalance the osmotic effect of the intracellular proteins. A high K+/Na+ ratio and hyperosmoticity, separately or together, were ineffective in the absence ofsuch a solute and unnecessary in its presence. The most effective non-permeating solute tested was polyethylene glycol, mol. wt. 20,000 cells stored in a 1% solution of this in phosphate buffered balanced salt solution remained viable for at least 24 hours and could subsequently be grown in culture.", "contents": "Factors influencing the survival of cell monolayers during storage at 4 degrees. As a step towards the definition of a medium suitable for long-term storage of potential organ transplants, a study was made of the effects of various solutions on the viability of monolayers of cells stored at 4 degrees. It was found that, for these to survive for more than a few hours, an essential component of the medium was a non-toxic solute which did not cross the cell membrane at low temperatures and could therefore counterbalance the osmotic effect of the intracellular proteins. A high K+/Na+ ratio and hyperosmoticity, separately or together, were ineffective in the absence ofsuch a solute and unnecessary in its presence. The most effective non-permeating solute tested was polyethylene glycol, mol. wt. 20,000 cells stored in a 1% solution of this in phosphate buffered balanced salt solution remained viable for at least 24 hours and could subsequently be grown in culture."} {"id": "PMID:1268046", "title": "The pathogenesis and pathology of experimental Quaranfil virus infection.", "content": "Mice were infected intranasally with Quaranfil arbovirus, and killed at intervals from 1 day to 2 months later. The infection produced clinical signs of neurological disturbance and a highly mortality. The virus could be isolated from the lungs on Days 1-9 and from the brain on Days 1-11 of the infection. Meningoencephalitis developed by Day 5 in the olfactory lobes and spread progressively caudally, involving all regions of the brain by Day 7. The prinicipal features of the inflammatory process were perivascular cuffing, necrosis of neurones, and, in the later stages, spongiform degeneration and marked astrocytic and microglial activity. In the lungs after a short and mild exudative phase interstitial pneumonia developed. This was characterized by proliferation of connective tissue cells in interalveolar septa and later by fibrosis.", "contents": "The pathogenesis and pathology of experimental Quaranfil virus infection. Mice were infected intranasally with Quaranfil arbovirus, and killed at intervals from 1 day to 2 months later. The infection produced clinical signs of neurological disturbance and a highly mortality. The virus could be isolated from the lungs on Days 1-9 and from the brain on Days 1-11 of the infection. Meningoencephalitis developed by Day 5 in the olfactory lobes and spread progressively caudally, involving all regions of the brain by Day 7. The prinicipal features of the inflammatory process were perivascular cuffing, necrosis of neurones, and, in the later stages, spongiform degeneration and marked astrocytic and microglial activity. In the lungs after a short and mild exudative phase interstitial pneumonia developed. This was characterized by proliferation of connective tissue cells in interalveolar septa and later by fibrosis."} {"id": "PMID:1268047", "title": "Acute and protracted changes in the liver of Syrian hamsters induced by a single dose of aflatoxin B1. Observations on pathological effects of the solvent (dimethylformamide).", "content": "Male Syrian hamsters, 8-10 weeks of age, were treated with a single intraperitoneal injection of crystalline aflatoxin B1 in solution of N -N -Dimethylformamide (DMF). The concentrations of aflatoxin were adjusted to the smallest controllable amount of solvent in relation to the size of the animal (0-5 or 1-0 ml/kg). Treatment with, respectively, 5-0 or 2-5 mg/kg aflatoxin in 1-0 ml/kg DMF was lethal to most animals within one week. However, reduction of the solvent to 0-5 ml/kg, while not eliminating the mortality entirely during the first week, made possible observation of the survivors up to 28 days. Hamsters appear to be more susceptible to DMF poisoning than other species, like rat, guinea-pig and rabbit in which this solvent was used by investigators on the biological effects of aflatoxin. Either dose given of DMF alone was lethal for several animals during the first week of observation and sufficient to produce histological lesions in the liver which were characteristic and clearly different from those induced by aflatoxin during the same period. DMF alone caused centrilobular necrosis which was accompanied by haemosiderosis of liver structures. With a aflatoxin, in addition, periportal and midzonal necrosis of the liver was present. Aflatoxin B1 and B1 and DMF both induce haemorrhagic tendency probably involvement in the coagulation process of the blood. It cannot be decided, however, at present whether this is the result of an indentical mechanism.", "contents": "Acute and protracted changes in the liver of Syrian hamsters induced by a single dose of aflatoxin B1. Observations on pathological effects of the solvent (dimethylformamide). Male Syrian hamsters, 8-10 weeks of age, were treated with a single intraperitoneal injection of crystalline aflatoxin B1 in solution of N -N -Dimethylformamide (DMF). The concentrations of aflatoxin were adjusted to the smallest controllable amount of solvent in relation to the size of the animal (0-5 or 1-0 ml/kg). Treatment with, respectively, 5-0 or 2-5 mg/kg aflatoxin in 1-0 ml/kg DMF was lethal to most animals within one week. However, reduction of the solvent to 0-5 ml/kg, while not eliminating the mortality entirely during the first week, made possible observation of the survivors up to 28 days. Hamsters appear to be more susceptible to DMF poisoning than other species, like rat, guinea-pig and rabbit in which this solvent was used by investigators on the biological effects of aflatoxin. Either dose given of DMF alone was lethal for several animals during the first week of observation and sufficient to produce histological lesions in the liver which were characteristic and clearly different from those induced by aflatoxin during the same period. DMF alone caused centrilobular necrosis which was accompanied by haemosiderosis of liver structures. With a aflatoxin, in addition, periportal and midzonal necrosis of the liver was present. Aflatoxin B1 and B1 and DMF both induce haemorrhagic tendency probably involvement in the coagulation process of the blood. It cannot be decided, however, at present whether this is the result of an indentical mechanism."} {"id": "PMID:1268048", "title": "Veno-occlusive lesions in the liver of rats after prolonged feeding with palmyrah (Borassus flabellifer) flour.", "content": "Flour from the young shoot of the palmyrah palm (Borassus flabellifer) which is consumed by people in certain tropical countries, when fed for prolonged periods to adult male rats produced chronic hepatic lesions which included intraluminal fibrosis of the centrilobular and portal veins, bile duct proliferation, increase of reticulin and fibrosis. Thromboses of the hepatic veins was not seen. The vascular lesions commenced as a subendothelial swelling which projected into the lumen and in which collagen deposition ended in almost total obliteration of the lumen. No hepatic megalocytosis was seen. It is suggested that the toxic factor(s) responsible are different from the pyrrolizidine alkaloids and dimethylnitrosamine which have been well documented to produce similar lesions.", "contents": "Veno-occlusive lesions in the liver of rats after prolonged feeding with palmyrah (Borassus flabellifer) flour. Flour from the young shoot of the palmyrah palm (Borassus flabellifer) which is consumed by people in certain tropical countries, when fed for prolonged periods to adult male rats produced chronic hepatic lesions which included intraluminal fibrosis of the centrilobular and portal veins, bile duct proliferation, increase of reticulin and fibrosis. Thromboses of the hepatic veins was not seen. The vascular lesions commenced as a subendothelial swelling which projected into the lumen and in which collagen deposition ended in almost total obliteration of the lumen. No hepatic megalocytosis was seen. It is suggested that the toxic factor(s) responsible are different from the pyrrolizidine alkaloids and dimethylnitrosamine which have been well documented to produce similar lesions."} {"id": "PMID:1268049", "title": "The cell proliferation kinetics of psoriasis examined by three in vivo techniques.", "content": "The cell proliferation kinetics of the germinative compartment in psoriasis have been re-investigated with tritiated thymidine and vincristine techniques. The mean cell cycle durations calculated from an extended fraction of labelled mitoses experiment were Tc=56 h, t1=43 h, ts=7-7 h and t2=5-6 h. Combination of the results of the FLM experiment with the experimental labelling index and the experimental birth rate suggests a growth fraction of unity and an exponential age distribution for the germinative population. An exponential age distribution is supported by the presence of several layers of germinative cells and the direction of the mitotic axes during cell division.", "contents": "The cell proliferation kinetics of psoriasis examined by three in vivo techniques. The cell proliferation kinetics of the germinative compartment in psoriasis have been re-investigated with tritiated thymidine and vincristine techniques. The mean cell cycle durations calculated from an extended fraction of labelled mitoses experiment were Tc=56 h, t1=43 h, ts=7-7 h and t2=5-6 h. Combination of the results of the FLM experiment with the experimental labelling index and the experimental birth rate suggests a growth fraction of unity and an exponential age distribution for the germinative population. An exponential age distribution is supported by the presence of several layers of germinative cells and the direction of the mitotic axes during cell division."} {"id": "PMID:1268050", "title": "Simplification of local therapy of psoriasis with 8-methoxypsoralen. Methods and initial results.", "content": "Local 8-methoxypsoralen black-light treatment was carried out on sixty-two patients. For the first time, oil was employed as a preparation base in order to increase the transparency and so the effectiveness of irradiation. Also the need for a descaling pretreatment was avoided. In investigations still being carried out, 27.5% patients showed very good improvement, 48-4% good and 24-2% unsatisfactory results of treatment. In many cases, less than fifteen irradiation sessions were necessary for clinical healing. However, to obtain a uniform pigmentation, additional irradiation proved necessary.", "contents": "Simplification of local therapy of psoriasis with 8-methoxypsoralen. Methods and initial results. Local 8-methoxypsoralen black-light treatment was carried out on sixty-two patients. For the first time, oil was employed as a preparation base in order to increase the transparency and so the effectiveness of irradiation. Also the need for a descaling pretreatment was avoided. In investigations still being carried out, 27.5% patients showed very good improvement, 48-4% good and 24-2% unsatisfactory results of treatment. In many cases, less than fifteen irradiation sessions were necessary for clinical healing. However, to obtain a uniform pigmentation, additional irradiation proved necessary."} {"id": "PMID:1268051", "title": "Epidermal lipid metabolism in psoriasis and lichen simplex.", "content": "The rate and pattern of epidermal lipogenesis from [14C] glucose were measured in fifteen patients with psoriasis and three with lichen simplex, compared with twenty controls. In 'uninvolved' epidermis from psoriatic subjects the mean lipogenic rate was slightly raised, although the increase was not statistically significant. There was a positive correlation between overall lipogenic rate and the percentage of isotope appearing in free sterol, while the relative proportions of the other lipid classes were unchanged. By contrast, in control epidermis sterol percentage was negatively correlated with lipogenic rate. In psoriatic lesions total epidermal lipogenesis (per unit surface area) was raised compared with matched control 'uninvolved' epidermis. Also raised were percentage labelling of free sterol and of combined (free sterol and monoesters), and the free sterol: monoester ratio was increased. Similar findings were obtained with lesions of lichen simplex, suggesting that disturbed sterol metabolism may be a common feature in conditions of abnormal keratinization.", "contents": "Epidermal lipid metabolism in psoriasis and lichen simplex. The rate and pattern of epidermal lipogenesis from [14C] glucose were measured in fifteen patients with psoriasis and three with lichen simplex, compared with twenty controls. In 'uninvolved' epidermis from psoriatic subjects the mean lipogenic rate was slightly raised, although the increase was not statistically significant. There was a positive correlation between overall lipogenic rate and the percentage of isotope appearing in free sterol, while the relative proportions of the other lipid classes were unchanged. By contrast, in control epidermis sterol percentage was negatively correlated with lipogenic rate. In psoriatic lesions total epidermal lipogenesis (per unit surface area) was raised compared with matched control 'uninvolved' epidermis. Also raised were percentage labelling of free sterol and of combined (free sterol and monoesters), and the free sterol: monoester ratio was increased. Similar findings were obtained with lesions of lichen simplex, suggesting that disturbed sterol metabolism may be a common feature in conditions of abnormal keratinization."} {"id": "PMID:1268052", "title": "The natural history of trichilemmal cysts.", "content": "The histological features of 149 trichilemmal cysts removed from sixty-five patients are reviewed and related to the clinical findings. These cysts, which may be solitary or multiple, gradually increase in size and number, and may produce daughter cysts by budding. When a breach occurs in the wall, inflammatory cells pour in but do not replace the cyst wall. This event may be followed by healing from the margins of the breach, by marsupialization to the overlying epidermis and thus natural resolution, or by proliferation to produce a pseudo-epitheliomatous change which can be confused with a well differentiated squamous cell carcinoma.", "contents": "The natural history of trichilemmal cysts. The histological features of 149 trichilemmal cysts removed from sixty-five patients are reviewed and related to the clinical findings. These cysts, which may be solitary or multiple, gradually increase in size and number, and may produce daughter cysts by budding. When a breach occurs in the wall, inflammatory cells pour in but do not replace the cyst wall. This event may be followed by healing from the margins of the breach, by marsupialization to the overlying epidermis and thus natural resolution, or by proliferation to produce a pseudo-epitheliomatous change which can be confused with a well differentiated squamous cell carcinoma."} {"id": "PMID:1268053", "title": "Wegener's granulomatosis. Combined therapy with low-dosage systemic corticosteroids, azathioprine and cyclophosphamide in three patients.", "content": "Three patients with Wegener's granulomatosis are reported. All three had skin, nose, sinus, mouth and pulmonary lesions; one had severe renal involvement as well. In two patients combined treatment with low-dosage systemic corticosteroids, azathioprine, and cyclophosphamide resulted in rapid clinical improvement and complete disappearance of the skin, mouth, nasal, sinus and pulmonary lesions. In one of these two patients who had severe renal involvement, proteinuria greatly diminished and arrest of progression of renal insufficiency was observed. In the third patient combined treatment with azathioprine and cyclophosphamide resulted in complete remission of skin, mucous membrane, lung and sinus lesions. The patient with severe renal involvement is alive and ambulant 4 years after the onset of the disease, the other two are completely symptom-free and well 2 1/2 years and 1 year after the onset of their illnesses, respectively. These results confirm previous reports about the effectiveness of immunosuppressive and cytotoxic agents in Wegener's granulomatosis, the use of which seems to have improved the prognosis significantly in a disease previously considered to be fatal within 5 months.", "contents": "Wegener's granulomatosis. Combined therapy with low-dosage systemic corticosteroids, azathioprine and cyclophosphamide in three patients. Three patients with Wegener's granulomatosis are reported. All three had skin, nose, sinus, mouth and pulmonary lesions; one had severe renal involvement as well. In two patients combined treatment with low-dosage systemic corticosteroids, azathioprine, and cyclophosphamide resulted in rapid clinical improvement and complete disappearance of the skin, mouth, nasal, sinus and pulmonary lesions. In one of these two patients who had severe renal involvement, proteinuria greatly diminished and arrest of progression of renal insufficiency was observed. In the third patient combined treatment with azathioprine and cyclophosphamide resulted in complete remission of skin, mucous membrane, lung and sinus lesions. The patient with severe renal involvement is alive and ambulant 4 years after the onset of the disease, the other two are completely symptom-free and well 2 1/2 years and 1 year after the onset of their illnesses, respectively. These results confirm previous reports about the effectiveness of immunosuppressive and cytotoxic agents in Wegener's granulomatosis, the use of which seems to have improved the prognosis significantly in a disease previously considered to be fatal within 5 months."} {"id": "PMID:1268054", "title": "Challenge test battery in chronic urticaria.", "content": "The use of a battery of challenge tests in the routine investigations of patients with chronic urticaria has an important place, demonstrating an exacerbating factor in over half the patients. Diets designed to reduce the ingestion of the substances concerned are associated with clearing or considerable improvements in 75% of the patients treated.", "contents": "Challenge test battery in chronic urticaria. The use of a battery of challenge tests in the routine investigations of patients with chronic urticaria has an important place, demonstrating an exacerbating factor in over half the patients. Diets designed to reduce the ingestion of the substances concerned are associated with clearing or considerable improvements in 75% of the patients treated."} {"id": "PMID:1268055", "title": "Histological aspects of DNCB sensitization and challenge tests.", "content": "I. A group of twenty-one Caucasian volunteers was patch tested without preliminary sensitization with 3, 10, 30, 50 and 90 mug 2,4-dinitrochlorobenzene (DNCB)/cm2. Of this group seven persons were read after 24 h; with one exception all showed a toxic erythematous reaction to 30 mug and higher amounts of DNCB/cm2. The other fourteen volunteers were read after 48 h. All except one reacted positively to 30 mug and higher amounts of DNCB/cm2. Histologically no changes could be noted after application of 3 and 10 mug DNCB/cm2; they started to appear in patch tests with 30 mug DNCB/cm2 or more. II. A second group of twenty-one Caucasian volunteers was sensitized with 2000 mug DNCB on a surface area of 3-14 cm2. Biopsies were performed after 1 h, 5 h, 1 day and then daily for 17 days. The histological changes occurring in the sensitization site during the primary irritant reaction of the first days were compared with the changes occurring during the flare-up reaction. No essential qualitative differences could be noted. III. Four Caucasian volunteers were sensitized with 2000 mug DNCB on 3-14 cm2. Fourteen days later challenge patch test doses of 3, 10, 30, 50 and 90 mug DNCB/cm2 were applied. Biopsies of the challenge sites were performed after 48 h. In contrast to the results in group I, histological changes could already be noted after challenge patch tests with 3 mug DNCB/cm2. The nature ofthe histological changes in primary irritant and allergic reactions to DNCB appeared to be identical and consisted of spongiosis, epidermal degeneration and lymphocytic infiltration around vessles and epidermal appendages and penetrating into the epidermal layers. It is concluded that, in order to avoid errors through misinterpretation, challenge patch tests with DNCB must be performed with low amounts, e.g. 3 or 10 mug/cm2.", "contents": "Histological aspects of DNCB sensitization and challenge tests. I. A group of twenty-one Caucasian volunteers was patch tested without preliminary sensitization with 3, 10, 30, 50 and 90 mug 2,4-dinitrochlorobenzene (DNCB)/cm2. Of this group seven persons were read after 24 h; with one exception all showed a toxic erythematous reaction to 30 mug and higher amounts of DNCB/cm2. The other fourteen volunteers were read after 48 h. All except one reacted positively to 30 mug and higher amounts of DNCB/cm2. Histologically no changes could be noted after application of 3 and 10 mug DNCB/cm2; they started to appear in patch tests with 30 mug DNCB/cm2 or more. II. A second group of twenty-one Caucasian volunteers was sensitized with 2000 mug DNCB on a surface area of 3-14 cm2. Biopsies were performed after 1 h, 5 h, 1 day and then daily for 17 days. The histological changes occurring in the sensitization site during the primary irritant reaction of the first days were compared with the changes occurring during the flare-up reaction. No essential qualitative differences could be noted. III. Four Caucasian volunteers were sensitized with 2000 mug DNCB on 3-14 cm2. Fourteen days later challenge patch test doses of 3, 10, 30, 50 and 90 mug DNCB/cm2 were applied. Biopsies of the challenge sites were performed after 48 h. In contrast to the results in group I, histological changes could already be noted after challenge patch tests with 3 mug DNCB/cm2. The nature ofthe histological changes in primary irritant and allergic reactions to DNCB appeared to be identical and consisted of spongiosis, epidermal degeneration and lymphocytic infiltration around vessles and epidermal appendages and penetrating into the epidermal layers. It is concluded that, in order to avoid errors through misinterpretation, challenge patch tests with DNCB must be performed with low amounts, e.g. 3 or 10 mug/cm2."} {"id": "PMID:1268056", "title": "A case of Pyemotes dermatitis. With a note on the role of these mites in skin disease.", "content": "Acute dermatitis developed in a fisherman after contact with old cherry-wood. A Pyemotes mite, probably P. beckeri, found in the wood, was thought to be responsible--thus illustrating the importance of appropriate laboratory examinations for ectoparasites. Human skin erruptions caused by indigenous, in contrast to imported, Pyemotes species have not previously been reported in Britain. These tarsonemoid mites attack small insect hosts and their possible role in dermatoses is discussed. Dermatitis caused by these mites is probably world-wide in distribution, but during the last century the confusing acarological nomenclature surrounding Pyemotes has resulted in an equally confusing variety of dermatological diagnoses.", "contents": "A case of Pyemotes dermatitis. With a note on the role of these mites in skin disease. Acute dermatitis developed in a fisherman after contact with old cherry-wood. A Pyemotes mite, probably P. beckeri, found in the wood, was thought to be responsible--thus illustrating the importance of appropriate laboratory examinations for ectoparasites. Human skin erruptions caused by indigenous, in contrast to imported, Pyemotes species have not previously been reported in Britain. These tarsonemoid mites attack small insect hosts and their possible role in dermatoses is discussed. Dermatitis caused by these mites is probably world-wide in distribution, but during the last century the confusing acarological nomenclature surrounding Pyemotes has resulted in an equally confusing variety of dermatological diagnoses."} {"id": "PMID:1268057", "title": "Mycobacterium marinum skin infections mimicking cutaneous leishmaniasis.", "content": "Ten cases of skin infection due to Mycobacterium marinum are reported from Israel. Most of the infections were contracted in natural bathing pools at Ein Feshka on the shores of the Dead Sea, south of Jericho. The lesions closely resembled those of cutaneous leishmaniasis prevalent in this region. The condition does not seem to have been detected previously in the Middle East.", "contents": "Mycobacterium marinum skin infections mimicking cutaneous leishmaniasis. Ten cases of skin infection due to Mycobacterium marinum are reported from Israel. Most of the infections were contracted in natural bathing pools at Ein Feshka on the shores of the Dead Sea, south of Jericho. The lesions closely resembled those of cutaneous leishmaniasis prevalent in this region. The condition does not seem to have been detected previously in the Middle East."} {"id": "PMID:1268058", "title": "Contact dermatitis from propolis.", "content": "Two patients with contact dermatitis due to the natural product propolis (bee glue) are reported. They presented perioral eczema and stomatitis which were recalcitrant until propolis was considered as the cause. Patch tests with propolis preparations were positive in both patients, and, furthermore, in the second patient the lesions relapsed after provocation tests. European standard patch test including balsam of Peru were negative. The complexity of propolis, its supposed anti-inflammatory effect due to flavonoids, and the sensitizing agents originating mainly from the poplar trees are discussed together with the cross-sensitization to balsam of Peru. Contact dermatitis due to propolis should be considered in unexplained eczemas, mainly perioral but also in other areas, as propolis preparations are available also as ointments and cosmetic creams.", "contents": "Contact dermatitis from propolis. Two patients with contact dermatitis due to the natural product propolis (bee glue) are reported. They presented perioral eczema and stomatitis which were recalcitrant until propolis was considered as the cause. Patch tests with propolis preparations were positive in both patients, and, furthermore, in the second patient the lesions relapsed after provocation tests. European standard patch test including balsam of Peru were negative. The complexity of propolis, its supposed anti-inflammatory effect due to flavonoids, and the sensitizing agents originating mainly from the poplar trees are discussed together with the cross-sensitization to balsam of Peru. Contact dermatitis due to propolis should be considered in unexplained eczemas, mainly perioral but also in other areas, as propolis preparations are available also as ointments and cosmetic creams."} {"id": "PMID:1268059", "title": "The pathology of lymphangioma circumscriptum.", "content": "A study of lymphangioma circumscriptum has been carried out over a number of years in an attempt to understand its nature and pathogenesis, with a view to improving treatment. It is postulated that the lesion consists essentially of a collection of large muscular-coated lymphatic cisterns, lying deep in the subcutaneous plane and communicating via dilated dermal lymphatics with the superficial vesicles. It seems that these cisterns do not communicate directly, if at all, with the general lymphatic system but represent a sequestrated part of it. They have been shown by cannulation to pulsate at a slow steady rate producing a rise and fall of pressure within them. It is believed that the vesicles are saccular dilatations of superficial lymphatics, secondary to raised pressure transmitted from the pulsating cisterns beneath. It is suggested that may be possible to treat these lesions more successfully and with better cosmetic results by excising the subcutaneous cisterns and leaving the overlying skin intact.", "contents": "The pathology of lymphangioma circumscriptum. A study of lymphangioma circumscriptum has been carried out over a number of years in an attempt to understand its nature and pathogenesis, with a view to improving treatment. It is postulated that the lesion consists essentially of a collection of large muscular-coated lymphatic cisterns, lying deep in the subcutaneous plane and communicating via dilated dermal lymphatics with the superficial vesicles. It seems that these cisterns do not communicate directly, if at all, with the general lymphatic system but represent a sequestrated part of it. They have been shown by cannulation to pulsate at a slow steady rate producing a rise and fall of pressure within them. It is believed that the vesicles are saccular dilatations of superficial lymphatics, secondary to raised pressure transmitted from the pulsating cisterns beneath. It is suggested that may be possible to treat these lesions more successfully and with better cosmetic results by excising the subcutaneous cisterns and leaving the overlying skin intact."} {"id": "PMID:1268060", "title": "Vascular changes in human skin after ultraviolet irradiation.", "content": "Blood-flow changes in human skin after ultraviolet irradiation at 250 and 300 nm have been measured by three separate methods. Those methods which measure overall blood-flow changes in the skin showed increased flow after irradiation at both wavelengths. A method which measured flow only in the superficial vessels showed a slight increase in flow after low doses of both wavelengths, but in contrast, after higher doses, this method showed a marked reduction in flow through the upper dermal vessels. This reduction in flow is probably due to stasis in these superficial vessels, perhaps secondary to vascular damage. Contrary to previous reports, blood-flow changes after irradiation at 250 and 300 nm are similar and may be mediated by identical mechanisms.", "contents": "Vascular changes in human skin after ultraviolet irradiation. Blood-flow changes in human skin after ultraviolet irradiation at 250 and 300 nm have been measured by three separate methods. Those methods which measure overall blood-flow changes in the skin showed increased flow after irradiation at both wavelengths. A method which measured flow only in the superficial vessels showed a slight increase in flow after low doses of both wavelengths, but in contrast, after higher doses, this method showed a marked reduction in flow through the upper dermal vessels. This reduction in flow is probably due to stasis in these superficial vessels, perhaps secondary to vascular damage. Contrary to previous reports, blood-flow changes after irradiation at 250 and 300 nm are similar and may be mediated by identical mechanisms."} {"id": "PMID:1268061", "title": "Phototoxic blisters from high frusemide dosage.", "content": "Blistering of exposed areas has appeared in patients suffering from chronic renal failure treated with high doses of frusemide. The blistering, which resembles that occurring in nalidixic acid phototoxicity and in porphyria cutanea tarda, is considered phototoxic in nature.", "contents": "Phototoxic blisters from high frusemide dosage. Blistering of exposed areas has appeared in patients suffering from chronic renal failure treated with high doses of frusemide. The blistering, which resembles that occurring in nalidixic acid phototoxicity and in porphyria cutanea tarda, is considered phototoxic in nature."} {"id": "PMID:1268062", "title": "Effect of the Hewitt keratinizing epidermal carcinoma on cell proliferation in different organs of the host mouse and in human psoriatic skin cultured in diffusion chambers.", "content": "Incorporation of 3H-thymidine into different squamous epithelia and other tissues was studied in mice bearing the Hewitt keratinizing epidermal carcinoma with a raised epidermal chalone content in the body. The results showed that DNA synthesis in the tumour-bearing mice was inhibited strongly in the epithelium of the ear (c.80%), moderately in the epithelium of the back skin and the foot (c.55%), and weakly in the epithelium of the tongue and the cornea (c.25%). These inhibitions appear to be specific in nature, because cell proliferation was not detectably affected in the sebaceous gland, intestinal epithelium, bone marrow, and thymus lymphocytes. Thymus size, however, was reduced in the tumour-bearing mice compared with controls, and 3H-thymidine uptake was depressed in the spleen and to some extent also in the lymph nodes, possibly owing to non-specific stress. Labelling index of human psoriatic epidermis was suppressed in diffusion-chamber cultures carried by the tumour-bearing host mice compared with controls. However, this reaction was probably not specific in nature, because the labelling index of mouse bone-marrow cells was also decreased when grown in tumour-bearing animals.", "contents": "Effect of the Hewitt keratinizing epidermal carcinoma on cell proliferation in different organs of the host mouse and in human psoriatic skin cultured in diffusion chambers. Incorporation of 3H-thymidine into different squamous epithelia and other tissues was studied in mice bearing the Hewitt keratinizing epidermal carcinoma with a raised epidermal chalone content in the body. The results showed that DNA synthesis in the tumour-bearing mice was inhibited strongly in the epithelium of the ear (c.80%), moderately in the epithelium of the back skin and the foot (c.55%), and weakly in the epithelium of the tongue and the cornea (c.25%). These inhibitions appear to be specific in nature, because cell proliferation was not detectably affected in the sebaceous gland, intestinal epithelium, bone marrow, and thymus lymphocytes. Thymus size, however, was reduced in the tumour-bearing mice compared with controls, and 3H-thymidine uptake was depressed in the spleen and to some extent also in the lymph nodes, possibly owing to non-specific stress. Labelling index of human psoriatic epidermis was suppressed in diffusion-chamber cultures carried by the tumour-bearing host mice compared with controls. However, this reaction was probably not specific in nature, because the labelling index of mouse bone-marrow cells was also decreased when grown in tumour-bearing animals."} {"id": "PMID:1268063", "title": "In vitro lymphocyte stimulation by wart antigen in man.", "content": "The lymphocyte transformation test was used to study cell-mediated immunity to wart antigen in patients with active wart infections, in patients with past history of warts and in control subjects. A common pattern was established with wart antigen; a control baseline, followed by a rise of 14C thymidine uptake in the 'active' group and a further elevation in the 'past history' group. Five patients with active warts were followed up and re-examined at various intervals after successful wart resolution; all except one responded to wart antigen by increased DNA synthetic activity after the wart resolution. This increased response was specific for wart antigen and could still be detected 6 months after wart resolution.", "contents": "In vitro lymphocyte stimulation by wart antigen in man. The lymphocyte transformation test was used to study cell-mediated immunity to wart antigen in patients with active wart infections, in patients with past history of warts and in control subjects. A common pattern was established with wart antigen; a control baseline, followed by a rise of 14C thymidine uptake in the 'active' group and a further elevation in the 'past history' group. Five patients with active warts were followed up and re-examined at various intervals after successful wart resolution; all except one responded to wart antigen by increased DNA synthetic activity after the wart resolution. This increased response was specific for wart antigen and could still be detected 6 months after wart resolution."} {"id": "PMID:1268064", "title": "Subcutaneous phycomycosis in Uganda.", "content": "This paper reports a further eighty cases of subcutaneous phycomycosis infection in Uganda seen between 1967 and 1974. This brings the number of reported cases from this country to over 140 and indicates an unusual frequency. The infection is more common in certain northern areas but does not appear to be confined to one ecological area. Suggestions are made as to possible factors in the initiation of this unusual infection.", "contents": "Subcutaneous phycomycosis in Uganda. This paper reports a further eighty cases of subcutaneous phycomycosis infection in Uganda seen between 1967 and 1974. This brings the number of reported cases from this country to over 140 and indicates an unusual frequency. The infection is more common in certain northern areas but does not appear to be confined to one ecological area. Suggestions are made as to possible factors in the initiation of this unusual infection."} {"id": "PMID:1268065", "title": "The effect of clobetasone butyrate and other topical steroids on skin thickness of the domestic pig.", "content": "A new glucocorticoid, clobetasone butyrate, has been shown in patients to have good topical anti-inflammatory activity and a minimal effect on hypothalamic-pituitary-adrenal function. Among a group of topically active corticosteroids, compared in a controlled study in the domestic pig, clobetasone butyrate is shown to cause less epidermal thinning than any of the others except only 1% hydrocortisone. This evidence of a lesser atrophogenic effect may indicate further dissociation of unwanted from wanted properties in clobetasone butyrate.", "contents": "The effect of clobetasone butyrate and other topical steroids on skin thickness of the domestic pig. A new glucocorticoid, clobetasone butyrate, has been shown in patients to have good topical anti-inflammatory activity and a minimal effect on hypothalamic-pituitary-adrenal function. Among a group of topically active corticosteroids, compared in a controlled study in the domestic pig, clobetasone butyrate is shown to cause less epidermal thinning than any of the others except only 1% hydrocortisone. This evidence of a lesser atrophogenic effect may indicate further dissociation of unwanted from wanted properties in clobetasone butyrate."} {"id": "PMID:1268066", "title": "Cell division and metabolic activity of naevus cells. The relationships between anatomy and behaviour in moles.", "content": "Thirty moles have been studied by in vitro techniques employing tritiated precursor compounds in order to demonstrate replicative and metabolic activity in naevus cells. Autoradiographs prepared from the incubated tissue showed that replicative activity occurred at all anatomical levels within the naevi. Synthesis of macro-molecules also occurred throughout the mole, but more actively in the junctional and superficial zones. The term 'Junctional Activity' does not appear to have any meaning in cell kinetic terms, and is not associated with any proliferative capacity.", "contents": "Cell division and metabolic activity of naevus cells. The relationships between anatomy and behaviour in moles. Thirty moles have been studied by in vitro techniques employing tritiated precursor compounds in order to demonstrate replicative and metabolic activity in naevus cells. Autoradiographs prepared from the incubated tissue showed that replicative activity occurred at all anatomical levels within the naevi. Synthesis of macro-molecules also occurred throughout the mole, but more actively in the junctional and superficial zones. The term 'Junctional Activity' does not appear to have any meaning in cell kinetic terms, and is not associated with any proliferative capacity."} {"id": "PMID:1268067", "title": "Primary amyloidosis and myelomatosis associated with excessive fibrinolytic acitivty.", "content": "A case of primary amyloidosis is described in association with Bence-Jones myeloma and increased fibrinolytic activity. Epsilon aminocaproic acid reversed the fibrinolytic activity and clinical improvement was maintained with melphalan and prednisolone.", "contents": "Primary amyloidosis and myelomatosis associated with excessive fibrinolytic acitivty. A case of primary amyloidosis is described in association with Bence-Jones myeloma and increased fibrinolytic activity. Epsilon aminocaproic acid reversed the fibrinolytic activity and clinical improvement was maintained with melphalan and prednisolone."} {"id": "PMID:1268069", "title": "Clobetasol propionate ointment compared with dithranol in Lassar's paste in the treatment of psoriasis.", "content": "The initial results on ten patients in a trial of clobetasol propionate (Dermovate) ointment compared with dithranol in Lassar's paste are described. The rates of clearing for each preparation in each patient were not noticeably different. Relapse was slower with clobetasol propionate in all but one patient for whom there was no preference. The results are highly significant (P less than 0-005).", "contents": "Clobetasol propionate ointment compared with dithranol in Lassar's paste in the treatment of psoriasis. The initial results on ten patients in a trial of clobetasol propionate (Dermovate) ointment compared with dithranol in Lassar's paste are described. The rates of clearing for each preparation in each patient were not noticeably different. Relapse was slower with clobetasol propionate in all but one patient for whom there was no preference. The results are highly significant (P less than 0-005)."} {"id": "PMID:1268070", "title": "Experimentally induced steroid atrophy in the domestic pig and man.", "content": "A histological method of ranking topical steroid preparations according to the degree of epidermal thinning they cause in pig skin has been shown to be applicable to human skin. A 0-05% ointment of the new compound, clobetasone butyrate (Molivate), has been shown to cause less thinning than either fluocinolone acetonide 0-025% (Synalar) or flurandrenolone 0-0125% (Haelan) when applied without the use of occlusive dressings for 3 weeks to the human forearm.", "contents": "Experimentally induced steroid atrophy in the domestic pig and man. A histological method of ranking topical steroid preparations according to the degree of epidermal thinning they cause in pig skin has been shown to be applicable to human skin. A 0-05% ointment of the new compound, clobetasone butyrate (Molivate), has been shown to cause less thinning than either fluocinolone acetonide 0-025% (Synalar) or flurandrenolone 0-0125% (Haelan) when applied without the use of occlusive dressings for 3 weeks to the human forearm."} {"id": "PMID:1268071", "title": "Steroid-induced atrophy in an animal and human model.", "content": "A ratchet-controlled micrometer screw gauge has been used to measure the changes in skin thickness produced by topical corticosteroids. Measurable thinning of the mouse ear followed repeated daily application of corticosteroids. This response in the animal was used to assess the atrophic potential in a variety of standard formulations. The same compounds were applied to human skin and the changes in thickness measured. Patterns of response and the rank order of thinning obtained from the animal model were found to parallel closely the human results.", "contents": "Steroid-induced atrophy in an animal and human model. A ratchet-controlled micrometer screw gauge has been used to measure the changes in skin thickness produced by topical corticosteroids. Measurable thinning of the mouse ear followed repeated daily application of corticosteroids. This response in the animal was used to assess the atrophic potential in a variety of standard formulations. The same compounds were applied to human skin and the changes in thickness measured. Patterns of response and the rank order of thinning obtained from the animal model were found to parallel closely the human results."} {"id": "PMID:1268075", "title": "The pharmacological properties of corticosteroids in relation to clinical efficacy.", "content": "The pharmacological properties of cortisol (and cortisol-like drugs) are divided into several distinct activities according to the type and cellular site of action of the hormone. To each of these discrete properties is allotted the separate clinical beneficial responses and the adverse effects that probably arise from them. For any one patient only one, or two, of these pharmacological properties are desirable and the remainder are undesirable. Therapy aims to separate the wanted from unwanted effects and this can be attempted in three ways: firstly, by adjustment of dose, frequency and duration of corticosteroid administration; secondly by delivery of the drug directly only to the site of disease--if this is possible; and thirdly, by using analogues which have been synthesized with 'tailor-made' selective actions. Synthetic analogues have not yet offered much selectivity of action of value for systemic use, but for local use (as on the skin and in the respiratory tract) such analogues have provided a considerable therapeutic advance. It is suggested that the several distinctive pharmacological properties of cortisol (as well as the existence of other steroids closely related chemically but with widely different biological activities, such as progestagens and anaesthetics) offer hope for the synthesis of cortisol-like compounds with much greater selectivity in systemic action.", "contents": "The pharmacological properties of corticosteroids in relation to clinical efficacy. The pharmacological properties of cortisol (and cortisol-like drugs) are divided into several distinct activities according to the type and cellular site of action of the hormone. To each of these discrete properties is allotted the separate clinical beneficial responses and the adverse effects that probably arise from them. For any one patient only one, or two, of these pharmacological properties are desirable and the remainder are undesirable. Therapy aims to separate the wanted from unwanted effects and this can be attempted in three ways: firstly, by adjustment of dose, frequency and duration of corticosteroid administration; secondly by delivery of the drug directly only to the site of disease--if this is possible; and thirdly, by using analogues which have been synthesized with 'tailor-made' selective actions. Synthetic analogues have not yet offered much selectivity of action of value for systemic use, but for local use (as on the skin and in the respiratory tract) such analogues have provided a considerable therapeutic advance. It is suggested that the several distinctive pharmacological properties of cortisol (as well as the existence of other steroids closely related chemically but with widely different biological activities, such as progestagens and anaesthetics) offer hope for the synthesis of cortisol-like compounds with much greater selectivity in systemic action."} {"id": "PMID:1268076", "title": "Acute tolerance to effects of topical glucocorticosteroids.", "content": "Tachyphylaxis (acute tolerance) to two important actions of topical glucocorticosteroids is demonstrated. In humans, topically active glucocorticoids applied to the skin cause vasoconstriction initially but this response fades with successive applications. In hairless mouse epidermis, inhibition of DNA synthesis and mitosis is caused by one application of a glucocorticoid but with repeated administration of the drug this effect is lost. The degree of inhibition of cell division appears to be similar 30 and 54 h after one application of steroid to that following three or five applications during such a time period. These findings suggest that an optimum therapeutic approach to the use of these agents exists.", "contents": "Acute tolerance to effects of topical glucocorticosteroids. Tachyphylaxis (acute tolerance) to two important actions of topical glucocorticosteroids is demonstrated. In humans, topically active glucocorticoids applied to the skin cause vasoconstriction initially but this response fades with successive applications. In hairless mouse epidermis, inhibition of DNA synthesis and mitosis is caused by one application of a glucocorticoid but with repeated administration of the drug this effect is lost. The degree of inhibition of cell division appears to be similar 30 and 54 h after one application of steroid to that following three or five applications during such a time period. These findings suggest that an optimum therapeutic approach to the use of these agents exists."} {"id": "PMID:1268077", "title": "Steroid structure and steroid activity.", "content": "The diverse biological effects associated with naturally occurring steroids are reviewed, with particular reference to the effect upon biological activity of changes in chemical structure. The motives for synthetic modification of the natural products are discussed and are illustrated by reference to the development of systemic and topical anti-inflammatory agents, with improved potency and reduced side-effects.", "contents": "Steroid structure and steroid activity. The diverse biological effects associated with naturally occurring steroids are reviewed, with particular reference to the effect upon biological activity of changes in chemical structure. The motives for synthetic modification of the natural products are discussed and are illustrated by reference to the development of systemic and topical anti-inflammatory agents, with improved potency and reduced side-effects."} {"id": "PMID:1268079", "title": "The effect of percutaneously absorbed steroids on hypothalamic--pituitary--adrenal function after intensive use in in-patients.", "content": "Hypothalamic-pituitary-adrenal (HPA) axis function has been monitored in adults and children who required intensive treatment of their skin disease with topical corticosteroid preparations while in hospital. Evidence of mild suppression of the HPA axis was seen in adults when the more potent topical steroids were used, but recovery of function was rapid when the intensive treatment ceased. In children suppression was still present in twelve of sixteen cases on the 2nd day after treatment with 0-1% betamethasone 17-valerate ointment had stopped, yet in nine cases treated in a comparable manner with 1% hydrocortisone acetate ointment, there was no evidence of impaired HPA axis function.", "contents": "The effect of percutaneously absorbed steroids on hypothalamic--pituitary--adrenal function after intensive use in in-patients. Hypothalamic-pituitary-adrenal (HPA) axis function has been monitored in adults and children who required intensive treatment of their skin disease with topical corticosteroid preparations while in hospital. Evidence of mild suppression of the HPA axis was seen in adults when the more potent topical steroids were used, but recovery of function was rapid when the intensive treatment ceased. In children suppression was still present in twelve of sixteen cases on the 2nd day after treatment with 0-1% betamethasone 17-valerate ointment had stopped, yet in nine cases treated in a comparable manner with 1% hydrocortisone acetate ointment, there was no evidence of impaired HPA axis function."} {"id": "PMID:1268080", "title": "Measuring adrenal function in out-patients using topical corticosteroids.", "content": "A number of studies describing the effects on pituitary adrenal function of topically applied corticosteroids are reviewed. It is concluded that the adrenal function of the majority of out-patients is little affected by treatment with correctly prescribed topical corticosteroids. However, where patients need brief periods of treatment with large quantities of potent topical corticosteroids for extensive disease, clinicians should be aware of the possibility of transient adrenal suppression.", "contents": "Measuring adrenal function in out-patients using topical corticosteroids. A number of studies describing the effects on pituitary adrenal function of topically applied corticosteroids are reviewed. It is concluded that the adrenal function of the majority of out-patients is little affected by treatment with correctly prescribed topical corticosteroids. However, where patients need brief periods of treatment with large quantities of potent topical corticosteroids for extensive disease, clinicians should be aware of the possibility of transient adrenal suppression."} {"id": "PMID:1268084", "title": "A hypothesis for the increased oxygen affinity in haemoglobin Malm\u00f6.", "content": "Haemoglobin Malm\u00f6beta97His leads to Gln, a high oxygen affinity haemoglobin which causes secondary erythrocytosis, is transmitted in an autosomal dominant manner. A hypothesis accounting for the high oxygen affinity, hyperbolic oxyhaemoglobin dissociation curve, and the relatively normal Bohr effect is presented. The purified abnormal haemoglobin from the present family provided biochemical and functional data for this hypothesis based on the allosteric model proposed by Perutz. Experimental results support the formation of a chemical bond between the -SH proton of the beta93 cysteine and the amide of oxygen of the substituted beta97 glutamine as an explanation for the high oxygen affinity of haemoglobin Malm\u00f6.", "contents": "A hypothesis for the increased oxygen affinity in haemoglobin Malm\u00f6. Haemoglobin Malm\u00f6beta97His leads to Gln, a high oxygen affinity haemoglobin which causes secondary erythrocytosis, is transmitted in an autosomal dominant manner. A hypothesis accounting for the high oxygen affinity, hyperbolic oxyhaemoglobin dissociation curve, and the relatively normal Bohr effect is presented. The purified abnormal haemoglobin from the present family provided biochemical and functional data for this hypothesis based on the allosteric model proposed by Perutz. Experimental results support the formation of a chemical bond between the -SH proton of the beta93 cysteine and the amide of oxygen of the substituted beta97 glutamine as an explanation for the high oxygen affinity of haemoglobin Malm\u00f6."} {"id": "PMID:1268085", "title": "Lack of association between the HL-A system and pernicious anaemia.", "content": "Fifty-two patients with pernicious anaemia have been typed for the histocompatibility antigens. No association was found with any particular antigen.", "contents": "Lack of association between the HL-A system and pernicious anaemia. Fifty-two patients with pernicious anaemia have been typed for the histocompatibility antigens. No association was found with any particular antigen."} {"id": "PMID:1268086", "title": "Relationship between paraprotein polymerization and clinical features in IgA myeloma.", "content": "The clinical manifestation fo IgA multiple myeloma are usually not considered distinguishable from those of IgG myeloma despite the fact that IgA differs from IgG in several characteristics, particularly molecular size heterogeneity. The clinical and laboratory features of 25 patients with IgA myeloma seen during a 5 year period are presented. The degree of paraprotein polymerization was observed to vary greatly in these patients but remained chronologically constant in six individuals studied on several occasions over this period. The patients were divided into two groups on the basis of the degree of paraprotein polymerization. The first group comprised those patients in whom the IgA paraprotein was greater than 50% polymerized, whilst in the second group the paraprotein was predominantly monomeric. No clinical or pathological differences were seen between the 'polymeric' and 'monomeric' groups of myeloma apart from that directly attributable to the physicochemical effect of the paraprotein polymerization. Thus, five patients out of 11 of the 'polymeric' group had developed the hyperviscosity syndrome, whilst no patients in the 'monomeric' group had developed this complication. The concentration of the paraprotein during the course of the disease was comparable in both groups. This syndrome is considered to be relatively common in IgA myeloma and adds to the morbidity and mortality of the disease. Its anticipation and treatment may improve the quality and survival of patients likely to develop this complication.", "contents": "Relationship between paraprotein polymerization and clinical features in IgA myeloma. The clinical manifestation fo IgA multiple myeloma are usually not considered distinguishable from those of IgG myeloma despite the fact that IgA differs from IgG in several characteristics, particularly molecular size heterogeneity. The clinical and laboratory features of 25 patients with IgA myeloma seen during a 5 year period are presented. The degree of paraprotein polymerization was observed to vary greatly in these patients but remained chronologically constant in six individuals studied on several occasions over this period. The patients were divided into two groups on the basis of the degree of paraprotein polymerization. The first group comprised those patients in whom the IgA paraprotein was greater than 50% polymerized, whilst in the second group the paraprotein was predominantly monomeric. No clinical or pathological differences were seen between the 'polymeric' and 'monomeric' groups of myeloma apart from that directly attributable to the physicochemical effect of the paraprotein polymerization. Thus, five patients out of 11 of the 'polymeric' group had developed the hyperviscosity syndrome, whilst no patients in the 'monomeric' group had developed this complication. The concentration of the paraprotein during the course of the disease was comparable in both groups. This syndrome is considered to be relatively common in IgA myeloma and adds to the morbidity and mortality of the disease. Its anticipation and treatment may improve the quality and survival of patients likely to develop this complication."} {"id": "PMID:1268088", "title": "Physiology and ultrastructure of the blood platelet following exposure to hydrogen peroxide.", "content": "Hydrogen peroxide in micromolar concentrations can induce shape change in human blood platelets, and can modify the aggregation and release reaction of these cells as induced by ADP or thrombin. In larger (millimolar) concentrations, H2O2 produces fusion of platelets with distortions in platelet morphology unlike those normally caused by aggregating agents. The production of H2O2 in vivo by granulocytes or other cells could influence the processes of haemostasis or thrombosis.", "contents": "Physiology and ultrastructure of the blood platelet following exposure to hydrogen peroxide. Hydrogen peroxide in micromolar concentrations can induce shape change in human blood platelets, and can modify the aggregation and release reaction of these cells as induced by ADP or thrombin. In larger (millimolar) concentrations, H2O2 produces fusion of platelets with distortions in platelet morphology unlike those normally caused by aggregating agents. The production of H2O2 in vivo by granulocytes or other cells could influence the processes of haemostasis or thrombosis."} {"id": "PMID:1268089", "title": "A standardized bioassay for platelet factor 3 released by kaolin.", "content": "The test for platelet factor 3 described by Hardisty & Hutton (1975) has been modified to conform to the usual design for a parallel-line bioassay. Manchester Comparative Thromboplastin has been used as assay Standard, allowing an arbitrary unit of activity to be adopted. However, experiments suggested that the platelet activity measured was different from tissue factor activity. Platelets are tested as platelet-rich plasma diluted in a standardized mixture of plasma and fibrinogen, so that differences between the clotting factors of the test samples are eliminated, as verified by experiments on haemophiliacs and patients on anticoagulant treatment. Sonication and repeated freezing and thawing of platelet-rich plasma showed that approximately 15% of the PF3 is released by kaolin. In vivo, a single dose of 600 mg of aspirin reduced the PR3-release to half the previous value in 2 h; initial values were regained in 5-8 days.", "contents": "A standardized bioassay for platelet factor 3 released by kaolin. The test for platelet factor 3 described by Hardisty & Hutton (1975) has been modified to conform to the usual design for a parallel-line bioassay. Manchester Comparative Thromboplastin has been used as assay Standard, allowing an arbitrary unit of activity to be adopted. However, experiments suggested that the platelet activity measured was different from tissue factor activity. Platelets are tested as platelet-rich plasma diluted in a standardized mixture of plasma and fibrinogen, so that differences between the clotting factors of the test samples are eliminated, as verified by experiments on haemophiliacs and patients on anticoagulant treatment. Sonication and repeated freezing and thawing of platelet-rich plasma showed that approximately 15% of the PF3 is released by kaolin. In vivo, a single dose of 600 mg of aspirin reduced the PR3-release to half the previous value in 2 h; initial values were regained in 5-8 days."} {"id": "PMID:1268090", "title": "Chloramphenicol induced inhibition of platelet protein synthesis: in vitro and in vivo studies.", "content": "Chloramphenicol (CAP), an antibiotic which causes various blood dyscrasias, was shown to inhibit in vitro protein synthesis of human blood platelets. The effect is dose- and time-dependent, it is reversible after incubation for 2 h, and is comparable with the suppression achieved by cycloheximide (CXM). Electron microscopic examination revealed swelling and destruction of mitochondria. Administration of CAP to dogs produced a progressive inhibition of platelet protein synthesis as shown by a reduction in the rate of [3H]leucine incorporation into protein. The maximal inhibitory effect of the antibiotic was reached 0.5-4.0 h after its administration, when minimal leucine incorporation values of 9-40% of the control were measured. The suppressive effect of CAP was followed by an overshoot in the incorporation of [3H]leucine, up to a maximum of 602% of the value at zero time of the experiment.", "contents": "Chloramphenicol induced inhibition of platelet protein synthesis: in vitro and in vivo studies. Chloramphenicol (CAP), an antibiotic which causes various blood dyscrasias, was shown to inhibit in vitro protein synthesis of human blood platelets. The effect is dose- and time-dependent, it is reversible after incubation for 2 h, and is comparable with the suppression achieved by cycloheximide (CXM). Electron microscopic examination revealed swelling and destruction of mitochondria. Administration of CAP to dogs produced a progressive inhibition of platelet protein synthesis as shown by a reduction in the rate of [3H]leucine incorporation into protein. The maximal inhibitory effect of the antibiotic was reached 0.5-4.0 h after its administration, when minimal leucine incorporation values of 9-40% of the control were measured. The suppressive effect of CAP was followed by an overshoot in the incorporation of [3H]leucine, up to a maximum of 602% of the value at zero time of the experiment."} {"id": "PMID:1268091", "title": "In vivo behaviour of homologous urea-soluble 131I-fibrin and 125I-fibrinogen in rabbits: the effect of fibrinolysis inhibition.", "content": "The in vivo behaviour of urea-soluble fibrin monomer (FM) was compared with that of fibrinogen in rabbits. Purified rabbit 125I-fibrinogen was injected into 36 unanaesthetized rabbits. Three days later the rabbits received either purified rabbit 131I-FM I mg/kg body weight, which corresponds to cI% of the circulating plasma fibrinogen pool 131I-fibrinogen, or buffered urea only. The distribution volume of FM was 43.4 +/- 6.9 ml/kg and of fibrinogen 43.5 +/- 7.7 ml/kg (mean +/- SD). The elimination curve of urea-soluble FM as represented by the clottable 131I-radioactivity. plotted on a semi-logarithmic paper, consisted of an initial steep decay within the first 6 h and a slow flattening of the slope 6 to 24 h after injection of FM. Although a terminal single-exponential slope, as observed in fibrinogen elimination, could not be computed for the 24 h following FM injection the mean half-life time of the last segment of the clottable-radioactivity curve, between 12 h and 24 h, was 12 h. Within 24 h a mean of 83-5% of the injected FM were removed from the circulating blood. The elimination characteristics of fibrinogen were not influenced by the injected FM. Control experiments showed that buffered 3.0 M urea, the solvent of FM, does not influence distribution volume and elimination of 125I-fibrinogen. The distribution of 131I as well as 125I-radioactivities in organs representing FM and fibrinogen respectively did not differ from each other. Elevated levels of 131I-radioactivity, however, were found in the urine after FM injection suggesting an accelerated elimination of FM in comparison to fibrinogen. Fibrinolysis inhibition with high doses of aprotinin did not significantly reduce the urinary excretion of 131I-radioactivity representing breakdown of FM. Furthermore, inhibition of the fibrinolytic system had no influence on the elimination characteristics of either fibrinogen or FM. In order to explain the results obtained in this study the following theory is proposed. Intravenously injected FM forms complexes with fibrinogen and fibrinolytic degradation products. The complexes continuously increase in size until they dissociate into fibrin oligomers and carrier proteins. The oligomers are eliminated whereas the carrier proteins recycle.", "contents": "In vivo behaviour of homologous urea-soluble 131I-fibrin and 125I-fibrinogen in rabbits: the effect of fibrinolysis inhibition. The in vivo behaviour of urea-soluble fibrin monomer (FM) was compared with that of fibrinogen in rabbits. Purified rabbit 125I-fibrinogen was injected into 36 unanaesthetized rabbits. Three days later the rabbits received either purified rabbit 131I-FM I mg/kg body weight, which corresponds to cI% of the circulating plasma fibrinogen pool 131I-fibrinogen, or buffered urea only. The distribution volume of FM was 43.4 +/- 6.9 ml/kg and of fibrinogen 43.5 +/- 7.7 ml/kg (mean +/- SD). The elimination curve of urea-soluble FM as represented by the clottable 131I-radioactivity. plotted on a semi-logarithmic paper, consisted of an initial steep decay within the first 6 h and a slow flattening of the slope 6 to 24 h after injection of FM. Although a terminal single-exponential slope, as observed in fibrinogen elimination, could not be computed for the 24 h following FM injection the mean half-life time of the last segment of the clottable-radioactivity curve, between 12 h and 24 h, was 12 h. Within 24 h a mean of 83-5% of the injected FM were removed from the circulating blood. The elimination characteristics of fibrinogen were not influenced by the injected FM. Control experiments showed that buffered 3.0 M urea, the solvent of FM, does not influence distribution volume and elimination of 125I-fibrinogen. The distribution of 131I as well as 125I-radioactivities in organs representing FM and fibrinogen respectively did not differ from each other. Elevated levels of 131I-radioactivity, however, were found in the urine after FM injection suggesting an accelerated elimination of FM in comparison to fibrinogen. Fibrinolysis inhibition with high doses of aprotinin did not significantly reduce the urinary excretion of 131I-radioactivity representing breakdown of FM. Furthermore, inhibition of the fibrinolytic system had no influence on the elimination characteristics of either fibrinogen or FM. In order to explain the results obtained in this study the following theory is proposed. Intravenously injected FM forms complexes with fibrinogen and fibrinolytic degradation products. The complexes continuously increase in size until they dissociate into fibrin oligomers and carrier proteins. The oligomers are eliminated whereas the carrier proteins recycle."} {"id": "PMID:1268092", "title": "Comparison of the coagulant activities of platelets and phospholipids.", "content": "The coagulant activities of various phospholipid preparations were compared with those of platelets. Folch phospholipid with maximal platelet factor 3 (PF3) activity produced long recalcified clotting times of relatively undiluted plasma in plastic tubes whereas untreated or ADP-treated platelets with minimal PF3 activity produced short clotting times in the same test system which is sensitive to activators of the contact system of intrinsic coagulation. Bell and Alton phospholipids with maximal PF3 activity produced recalcified clotting times similar to those in the presence of platelets. Bell and Alton phospholipids had tissue factor activity, but Folch phospholipid and platelets did not. Bell and Alton phospholipids and gum acacia (used as a vehicle in one of the preparations) activated factor XII as did platelets, but Folch phospholipid did not. The multiple coagulant activities of Bell and Alton phospholipids (i.e. PF3, tissue factor and contact activating) may account for the absence of coagulant superiority of platelets in the undiluted system in plastic tubes. The coagulant activities of platelets are also complex but different from Bell and Alton phospholipids whereas Folch phospholipid would appear to possess only PF3 activity.", "contents": "Comparison of the coagulant activities of platelets and phospholipids. The coagulant activities of various phospholipid preparations were compared with those of platelets. Folch phospholipid with maximal platelet factor 3 (PF3) activity produced long recalcified clotting times of relatively undiluted plasma in plastic tubes whereas untreated or ADP-treated platelets with minimal PF3 activity produced short clotting times in the same test system which is sensitive to activators of the contact system of intrinsic coagulation. Bell and Alton phospholipids with maximal PF3 activity produced recalcified clotting times similar to those in the presence of platelets. Bell and Alton phospholipids had tissue factor activity, but Folch phospholipid and platelets did not. Bell and Alton phospholipids and gum acacia (used as a vehicle in one of the preparations) activated factor XII as did platelets, but Folch phospholipid did not. The multiple coagulant activities of Bell and Alton phospholipids (i.e. PF3, tissue factor and contact activating) may account for the absence of coagulant superiority of platelets in the undiluted system in plastic tubes. The coagulant activities of platelets are also complex but different from Bell and Alton phospholipids whereas Folch phospholipid would appear to possess only PF3 activity."} {"id": "PMID:1268093", "title": "Clinical and haematological data in 254 cases of beta-thalassaemia trait in Italy.", "content": "The haematological and clinical data in 254 Italian subjects with beta-thalassaemia trait are reported. 46% of the patients were anaemic, 40% complained of weakness, 19% showed enlargement of the spleen and 10% enlargement of the liver. The haemoglobin levels ranged from 8 to 15.5 g/dl with a normal distribution and a mean of 12.73 for males, 10.93 for females and 11.34 for children (4-15 years). Reticulocyte counts and serum bilirubin levels were slightly increased and both showed a statistically significant relationship with haemoglobin levels. The serum iron level was increased in 27% and decreased in 6% of the cases. Haemoglobin A2 concentrations ranged from 3.5% to 8% with a normal distribution and a mean of 5.37; Hb F values were less than 1% in 36% and varied from 1 to 14% in the remainder. Red cell osmotic fragility was decreased in all but 6% of the subjects: low MCV, MCH and MCHC values were observed in 75%, 86% and 10% respectively. A comparison is made between the data and those obtained by other workers.", "contents": "Clinical and haematological data in 254 cases of beta-thalassaemia trait in Italy. The haematological and clinical data in 254 Italian subjects with beta-thalassaemia trait are reported. 46% of the patients were anaemic, 40% complained of weakness, 19% showed enlargement of the spleen and 10% enlargement of the liver. The haemoglobin levels ranged from 8 to 15.5 g/dl with a normal distribution and a mean of 12.73 for males, 10.93 for females and 11.34 for children (4-15 years). Reticulocyte counts and serum bilirubin levels were slightly increased and both showed a statistically significant relationship with haemoglobin levels. The serum iron level was increased in 27% and decreased in 6% of the cases. Haemoglobin A2 concentrations ranged from 3.5% to 8% with a normal distribution and a mean of 5.37; Hb F values were less than 1% in 36% and varied from 1 to 14% in the remainder. Red cell osmotic fragility was decreased in all but 6% of the subjects: low MCV, MCH and MCHC values were observed in 75%, 86% and 10% respectively. A comparison is made between the data and those obtained by other workers."} {"id": "PMID:1268095", "title": "Activation of intravascular coagulation by endotoxin: the significance of granulocytes and platelets.", "content": "The importance of granulocytes and/or platelets in endotoxin-induced generalized intravascular coagulation was studied as well as thrombocytopenic rabbits. Neutropenia and thrombocytopenia were induced by oral administration of busulphan. Generalized intravascular coagulation, as indicated by renal glomerular microclot formation, was initiated by two intravenous injections of endotoxin. Granulocyte counts before the second injection of endotoxin were most significantly related to activation of intravascular coagulation whereas platelet counts either before the first or second injection of endotoxin were not definitely related to the activation process. Renal glomerular microclots occurred in rabbits after two injections of endotoxin even when the platelet counts were between 500 and 5000/mul. These experiments indicated that granulocytes but not platelets are essential to the activation of endotoxin-induced intravascular coagulation.", "contents": "Activation of intravascular coagulation by endotoxin: the significance of granulocytes and platelets. The importance of granulocytes and/or platelets in endotoxin-induced generalized intravascular coagulation was studied as well as thrombocytopenic rabbits. Neutropenia and thrombocytopenia were induced by oral administration of busulphan. Generalized intravascular coagulation, as indicated by renal glomerular microclot formation, was initiated by two intravenous injections of endotoxin. Granulocyte counts before the second injection of endotoxin were most significantly related to activation of intravascular coagulation whereas platelet counts either before the first or second injection of endotoxin were not definitely related to the activation process. Renal glomerular microclots occurred in rabbits after two injections of endotoxin even when the platelet counts were between 500 and 5000/mul. These experiments indicated that granulocytes but not platelets are essential to the activation of endotoxin-induced intravascular coagulation."} {"id": "PMID:1268096", "title": "A familial abnormality of circulating vitamin B12 binding proteins: occurrence in a family of high serum concentrations of transcobalamin II.", "content": "A family is described in which two members (a father and a daughter), both with quiescent ulcerative colitis, had abnormally high serum concentrations of a vitamin B12 binding protein. This protein had the molecular weight of transcobalamin II on gel filtration, and behaved like transcobalamin II with respect to its elution from DE-23 cellulose, its inhibition at acid pH, its absorption by uncoated charcoal, its binding by anti-TC II antibodies, and its ability to transfer vitamin B12 to transformed lymphocytes. Its plasma clearance and tissue distribution when injected into rabbits was indistinguishable from that of transcobalamin II from normal subjects. It migrated on electrophoresis in the beta, gamma region. This is the first case report of related subjects in whom high serum concentrations of transcobalamin II have been observed.", "contents": "A familial abnormality of circulating vitamin B12 binding proteins: occurrence in a family of high serum concentrations of transcobalamin II. A family is described in which two members (a father and a daughter), both with quiescent ulcerative colitis, had abnormally high serum concentrations of a vitamin B12 binding protein. This protein had the molecular weight of transcobalamin II on gel filtration, and behaved like transcobalamin II with respect to its elution from DE-23 cellulose, its inhibition at acid pH, its absorption by uncoated charcoal, its binding by anti-TC II antibodies, and its ability to transfer vitamin B12 to transformed lymphocytes. Its plasma clearance and tissue distribution when injected into rabbits was indistinguishable from that of transcobalamin II from normal subjects. It migrated on electrophoresis in the beta, gamma region. This is the first case report of related subjects in whom high serum concentrations of transcobalamin II have been observed."} {"id": "PMID:1268097", "title": "Effect of some anticonvulsant drugs on depletion of folate in rats on a vitamin B12-deficient diet.", "content": "Rats fed on vitamin B12-deficient or vitamin B12-supplemented diets and treated with phenobarbitone by intraperitoneal injection for 5 d showed significant increases in the activity of glutamate formiminotransferase in liver. The only significant depletion in liver folate activity was in vitamin B12-supplemented rats that were starved for 48 h. When rats were given the same diets, with phenobarbitone and diphenylhydantoin added, for 12 weeks or more in two separate experiments, significant increases in transferase activity were found only in the livers of animals fed on the deficient diet. However, there was significant depletion of liver folate in animals taking the supplemented diet.", "contents": "Effect of some anticonvulsant drugs on depletion of folate in rats on a vitamin B12-deficient diet. Rats fed on vitamin B12-deficient or vitamin B12-supplemented diets and treated with phenobarbitone by intraperitoneal injection for 5 d showed significant increases in the activity of glutamate formiminotransferase in liver. The only significant depletion in liver folate activity was in vitamin B12-supplemented rats that were starved for 48 h. When rats were given the same diets, with phenobarbitone and diphenylhydantoin added, for 12 weeks or more in two separate experiments, significant increases in transferase activity were found only in the livers of animals fed on the deficient diet. However, there was significant depletion of liver folate in animals taking the supplemented diet."} {"id": "PMID:1268098", "title": "Rheological properties of red cells in haemoglobin K\u00f6ln disease.", "content": "The rheological properties of erythrocytes of four patients with haemoglobin K\u00f6ln (Hb K\u00f6ln) disease were studied. Filtration of erythrocytes through polycarbonate sieves with a pore diameter of 5 mum and viscosity measurements of erythrocytes suspensions with a PCV of 80% were carried out. The rheological properties of erythrocytes of two of the patients were severely altered. In both patients an increased haemoglobin attachment to erythrocyte membranes resulting in a decreased filtration rate of erythrocytes was found. One of these cases had been splenectomized some years before. About half of the erythrocytes of this patient contained large Heinz bodies. Erythrocytes of this patient showed a decreased filtration rate and an increased viscosity. Moreover, erythrocytes of healthy adults containing Heinz bodies after incubation with acetylphenylhydrazine showed a decreased filtration rate as well as an increased viscosity. Membranes of erythrocytes of the other patients contained haemoglobin in an amount within the normal range of haemoglobin content of membranes of healthy adults. Erythrocytes of these patients showed normal rheological properties. The haemolytic process in these patients was only mild. We suggest that the amount of total haemoglobin attached to the erythrocyte membrane corresponds to the percentage of the unstable Hb K\u00f6ln present in the erythrocytes of the particular patient.", "contents": "Rheological properties of red cells in haemoglobin K\u00f6ln disease. The rheological properties of erythrocytes of four patients with haemoglobin K\u00f6ln (Hb K\u00f6ln) disease were studied. Filtration of erythrocytes through polycarbonate sieves with a pore diameter of 5 mum and viscosity measurements of erythrocytes suspensions with a PCV of 80% were carried out. The rheological properties of erythrocytes of two of the patients were severely altered. In both patients an increased haemoglobin attachment to erythrocyte membranes resulting in a decreased filtration rate of erythrocytes was found. One of these cases had been splenectomized some years before. About half of the erythrocytes of this patient contained large Heinz bodies. Erythrocytes of this patient showed a decreased filtration rate and an increased viscosity. Moreover, erythrocytes of healthy adults containing Heinz bodies after incubation with acetylphenylhydrazine showed a decreased filtration rate as well as an increased viscosity. Membranes of erythrocytes of the other patients contained haemoglobin in an amount within the normal range of haemoglobin content of membranes of healthy adults. Erythrocytes of these patients showed normal rheological properties. The haemolytic process in these patients was only mild. We suggest that the amount of total haemoglobin attached to the erythrocyte membrane corresponds to the percentage of the unstable Hb K\u00f6ln present in the erythrocytes of the particular patient."} {"id": "PMID:1268099", "title": "The relationship between total red cell volume, plasma volume and venous haematocrit.", "content": "Total red cell volume (TRCV) and plasma volume (PV) have been measured in 130 cases including 65 polycythaemic patients and 65 patients with a wide variety of disorders. Patients with gross splenomegaly were excluded from the study. The regression of TRCV on venous haematocrit (VHct) was found to be curvilinear, a single exponential function providing a good approximation ( r=0.92, P less than 0.001). No significant difference was found between the mean PVs of the polycythaemic and control groups (40.97 and 42.94 ml/kg respectively) although a slight but highly significant negative correlation was observed between PV and VHct (r = 0.47, P less than 0.001). This most marked for patients with VHcts below 0.30, for whom a separate plot yielded a correlation coefficient of 0.75. Total blood volume (TBV) and VHct were found to be positively correlated (r = 0.57, P less than 0.001) as would be expected from the TRCV and PV data. The significance of these findings is discussed.", "contents": "The relationship between total red cell volume, plasma volume and venous haematocrit. Total red cell volume (TRCV) and plasma volume (PV) have been measured in 130 cases including 65 polycythaemic patients and 65 patients with a wide variety of disorders. Patients with gross splenomegaly were excluded from the study. The regression of TRCV on venous haematocrit (VHct) was found to be curvilinear, a single exponential function providing a good approximation ( r=0.92, P less than 0.001). No significant difference was found between the mean PVs of the polycythaemic and control groups (40.97 and 42.94 ml/kg respectively) although a slight but highly significant negative correlation was observed between PV and VHct (r = 0.47, P less than 0.001). This most marked for patients with VHcts below 0.30, for whom a separate plot yielded a correlation coefficient of 0.75. Total blood volume (TBV) and VHct were found to be positively correlated (r = 0.57, P less than 0.001) as would be expected from the TRCV and PV data. The significance of these findings is discussed."} {"id": "PMID:1268101", "title": "Myocardial infarction in car assembly workers.", "content": "The incidence of myocardial infarction and the return to work for survivors were studied among the employees of an English car assembly plant by analysing 12 811 medical records of persons employed during the seven years between January 1966 and December 1972. The standardized morbidity ratio of myocardial infarction found in this study calculated on the basis of incidence rates reported by Kinlen )1973) for the Oxford community in which the factory was situated was 90. The standardized morbidity ratio from production line workers only was 66 and that for the monthly paid staff 272. Of the production line workers who survived the attack 22 (90%) returned to their previous jobs without undue difficulty and with two exceptions within four months of the onset of their illness; there was no relation between length of absence and age at the time of attack. These findings suggest that workers in mass production jobs such as car assembly are not special risk from myocardial infarction, and most of those who survive a heart attack are able to return to their former work. Taken with Kinlen's (1973) study and that of Armstrong et al. (1972) in Edinburgh, they also bear out mortality data by indicating that in Oxfordshire the incidence of coronary heart disease is lower than the British average.", "contents": "Myocardial infarction in car assembly workers. The incidence of myocardial infarction and the return to work for survivors were studied among the employees of an English car assembly plant by analysing 12 811 medical records of persons employed during the seven years between January 1966 and December 1972. The standardized morbidity ratio of myocardial infarction found in this study calculated on the basis of incidence rates reported by Kinlen )1973) for the Oxford community in which the factory was situated was 90. The standardized morbidity ratio from production line workers only was 66 and that for the monthly paid staff 272. Of the production line workers who survived the attack 22 (90%) returned to their previous jobs without undue difficulty and with two exceptions within four months of the onset of their illness; there was no relation between length of absence and age at the time of attack. These findings suggest that workers in mass production jobs such as car assembly are not special risk from myocardial infarction, and most of those who survive a heart attack are able to return to their former work. Taken with Kinlen's (1973) study and that of Armstrong et al. (1972) in Edinburgh, they also bear out mortality data by indicating that in Oxfordshire the incidence of coronary heart disease is lower than the British average."} {"id": "PMID:1268102", "title": "Significance of irregular small opacities in radiographs of coalminers in the USA.", "content": "The purpose of this study was to determine the factors that are associated with the occurrence of small irregular opacities in the chest radiographs of coalminers, and whether the lung function of miners with irregular opacities differed from that of miners with small rounded opacities, a mixture of small rounded and irregular opacities, or an absence of opacities. A subsample of 6166 coalminers was selected from 9076 miners who had been examined by the US Public Health Service as part of the National Study of Coalworkers' Pneumoconiosis. The subsample consisted of 4479 smokers and 1687 non-smokers. The chest radiograph of each miner was classified according to the UICC/Cincinnati Classification.", "contents": "Significance of irregular small opacities in radiographs of coalminers in the USA. The purpose of this study was to determine the factors that are associated with the occurrence of small irregular opacities in the chest radiographs of coalminers, and whether the lung function of miners with irregular opacities differed from that of miners with small rounded opacities, a mixture of small rounded and irregular opacities, or an absence of opacities. A subsample of 6166 coalminers was selected from 9076 miners who had been examined by the US Public Health Service as part of the National Study of Coalworkers' Pneumoconiosis. The subsample consisted of 4479 smokers and 1687 non-smokers. The chest radiograph of each miner was classified according to the UICC/Cincinnati Classification."} {"id": "PMID:1268103", "title": "Follow-up of ventilatory lung function in a group of cement workers.", "content": "In a group of 160 active cement workers and 80 control workers selected on the basis of having or not having symptoms of chronic bronchitis, forced vital capacity (FVC) and one second expiratory volume (FEV 1-0), both corrected for age and height, and ratio of one second forced expiratory volume to forced vital capacity (FEV 1-0/FVC (%)) were measured on two occasions with an interval of four and eight years respectively.", "contents": "Follow-up of ventilatory lung function in a group of cement workers. In a group of 160 active cement workers and 80 control workers selected on the basis of having or not having symptoms of chronic bronchitis, forced vital capacity (FVC) and one second expiratory volume (FEV 1-0), both corrected for age and height, and ratio of one second forced expiratory volume to forced vital capacity (FEV 1-0/FVC (%)) were measured on two occasions with an interval of four and eight years respectively."} {"id": "PMID:1268104", "title": "Induction of fibrogenesis by lung antibody-treated macrophages.", "content": "Using a modification of an in vitro model of fibrogenesis, lung connective tissue antibodies have been shown to stimulate macrophages to release a collagen stimulating factor acting on fibroblast target cells. This stimulation was measured by increased hydroxyproline production from fibroblasts that had reached stationary growth phase. In subcytotoxic amounts, this antibody had no such effect directly on fibroblasts. These findings further illustrate the value of studying fibrogenesis by the in vitro method.", "contents": "Induction of fibrogenesis by lung antibody-treated macrophages. Using a modification of an in vitro model of fibrogenesis, lung connective tissue antibodies have been shown to stimulate macrophages to release a collagen stimulating factor acting on fibroblast target cells. This stimulation was measured by increased hydroxyproline production from fibroblasts that had reached stationary growth phase. In subcytotoxic amounts, this antibody had no such effect directly on fibroblasts. These findings further illustrate the value of studying fibrogenesis by the in vitro method."} {"id": "PMID:1268105", "title": "Biochemical changes during the initial stages of industrial lead exposure.", "content": "Biochemical measurements were carried out on 20 workers entering employment in a lead industry. Blood lead (Pb-B) urinary delta-aminolevulinic acid (ALA), and coproporphyrin (CP) levels were determined before entry and then at approximately weekly intervals for the first 12 weeks of employment. Levels of blood lead began to increase in all men within one week rising from an average pre-employment figure of about 1-1 mumol/l (22 mug/100 ml) to a value of about 2-9 mumol/l (60 mug/100 ml) at three weeks. Subsequently there was only a small increase in Pb-B values levelled for the rest of the period.", "contents": "Biochemical changes during the initial stages of industrial lead exposure. Biochemical measurements were carried out on 20 workers entering employment in a lead industry. Blood lead (Pb-B) urinary delta-aminolevulinic acid (ALA), and coproporphyrin (CP) levels were determined before entry and then at approximately weekly intervals for the first 12 weeks of employment. Levels of blood lead began to increase in all men within one week rising from an average pre-employment figure of about 1-1 mumol/l (22 mug/100 ml) to a value of about 2-9 mumol/l (60 mug/100 ml) at three weeks. Subsequently there was only a small increase in Pb-B values levelled for the rest of the period."} {"id": "PMID:1268106", "title": "Activity of erythrocyte delta-aminolevulinic acid dehydrase and its change by heat treatment as indices of lead exposure.", "content": "The effect of heat treatment on erythrocyte delta-aminolevulinic acid dehydrase (ALAD) activity in the blood of human subjects was examined in relation to their lead exposure.", "contents": "Activity of erythrocyte delta-aminolevulinic acid dehydrase and its change by heat treatment as indices of lead exposure. The effect of heat treatment on erythrocyte delta-aminolevulinic acid dehydrase (ALAD) activity in the blood of human subjects was examined in relation to their lead exposure."} {"id": "PMID:1268107", "title": "Plasma concentrations of the oxime Pralidoxime Mesylate (P2S) after repeated oral and intramuscular administration.", "content": "The use of the oxime P2S as intravenous therapy for organophosphorus anticholinesterase poisoning is well known. In emergency situations this route of administration may prove impractical due to severe symptoms of anticholinesterase poisoning and therefore the intramuscular route is to be preferred. The absolute intramuscular dose of P2S per man, recommended as necessary for adequate therapy of anticholinesterase poisoning, is 500 mg. In practical situations this dose may have to be repeated at intervals resulting in overdosage, and therefore, the clinical side-effects which this regimen might have on normal subjects has been determined. It has also been suggested that where organophosphorus anticholinesterase compounds are handled continuously for many months in the year, for example, in crop spraying and in industry, P2S might be taken prophylactically.", "contents": "Plasma concentrations of the oxime Pralidoxime Mesylate (P2S) after repeated oral and intramuscular administration. The use of the oxime P2S as intravenous therapy for organophosphorus anticholinesterase poisoning is well known. In emergency situations this route of administration may prove impractical due to severe symptoms of anticholinesterase poisoning and therefore the intramuscular route is to be preferred. The absolute intramuscular dose of P2S per man, recommended as necessary for adequate therapy of anticholinesterase poisoning, is 500 mg. In practical situations this dose may have to be repeated at intervals resulting in overdosage, and therefore, the clinical side-effects which this regimen might have on normal subjects has been determined. It has also been suggested that where organophosphorus anticholinesterase compounds are handled continuously for many months in the year, for example, in crop spraying and in industry, P2S might be taken prophylactically."} {"id": "PMID:1268109", "title": "Absence attributed to sickness in oil tanker crews.", "content": "Absences attributed to sickness were investigated in 1410 deck and engine-room crew members during a period of two years and five months. The mean frequency of absences was 0-23 per man year, with a mean duration per absence of 41 days. The absence frequency varied with both rank and place of work. Altogether 23% of deck officers serving throughout the study and 43% of engine-room ratings had one or more absences. Spells of absence in young officers were five times more frequent when they were on leave than at sea. In the younger officers more than half of all spells that were initiated while on leave occurred at the end of the leave period. The contrasting environments of ship and shore allow the relative importance of effects on absence frequency of the work and home environment and of medical and social factors to be considered separately.", "contents": "Absence attributed to sickness in oil tanker crews. Absences attributed to sickness were investigated in 1410 deck and engine-room crew members during a period of two years and five months. The mean frequency of absences was 0-23 per man year, with a mean duration per absence of 41 days. The absence frequency varied with both rank and place of work. Altogether 23% of deck officers serving throughout the study and 43% of engine-room ratings had one or more absences. Spells of absence in young officers were five times more frequent when they were on leave than at sea. In the younger officers more than half of all spells that were initiated while on leave occurred at the end of the leave period. The contrasting environments of ship and shore allow the relative importance of effects on absence frequency of the work and home environment and of medical and social factors to be considered separately."} {"id": "PMID:1268120", "title": "The sleep habits, personality and academic performance of medical students.", "content": "The academic performance of 104 fourth-year medical students was assessed in relation to their sleep habits reported in a questionary and their scores on the Minnesota Multiphasic Personality Inventory. Poorer academic performance was related significantly to later times of waking up in the morning, particularly at weekends, and to subjectively poorer quality sleep, but not to the amount of sleep usually obtained. Poor academic performance was related also to scores on scales 3 (hysteria), 4 (psychopathic deviate) and 8 (schizophrenia) of the MMPI. Simple enquiries about sleep habits may make it easier for students who are at greatest risk of academic failure to be identified and helped.", "contents": "The sleep habits, personality and academic performance of medical students. The academic performance of 104 fourth-year medical students was assessed in relation to their sleep habits reported in a questionary and their scores on the Minnesota Multiphasic Personality Inventory. Poorer academic performance was related significantly to later times of waking up in the morning, particularly at weekends, and to subjectively poorer quality sleep, but not to the amount of sleep usually obtained. Poor academic performance was related also to scores on scales 3 (hysteria), 4 (psychopathic deviate) and 8 (schizophrenia) of the MMPI. Simple enquiries about sleep habits may make it easier for students who are at greatest risk of academic failure to be identified and helped."} {"id": "PMID:1268121", "title": "The prediction of medical student performance using in-course assessment.", "content": "The value of in-course assessment at King's College Hospital Medical School at predicting student performance at final qualifying examinations in medicine and surgery has been analysed. Only a small proportion of the variation in marks at finals could be explained by the factors studied. Both the MCQ and firm report methods of internal assessment used in the first clinical year were equally valuable at predicting final outcome. Performance at 2nd MB BS, the possession of another degree and the sequence of firm attachment in the first year have little predictive value. Female students are predicted to perform better in medicine than in surgery. The development of a more standardized quantifiable firm assessment looks potentially more valuable at predicting performance than refining the first year MCQ examinations.", "contents": "The prediction of medical student performance using in-course assessment. The value of in-course assessment at King's College Hospital Medical School at predicting student performance at final qualifying examinations in medicine and surgery has been analysed. Only a small proportion of the variation in marks at finals could be explained by the factors studied. Both the MCQ and firm report methods of internal assessment used in the first clinical year were equally valuable at predicting final outcome. Performance at 2nd MB BS, the possession of another degree and the sequence of firm attachment in the first year have little predictive value. Female students are predicted to perform better in medicine than in surgery. The development of a more standardized quantifiable firm assessment looks potentially more valuable at predicting performance than refining the first year MCQ examinations."} {"id": "PMID:1268122", "title": "The attainment of specified objectives by medical students in different learning environments.", "content": "Medical students were provided with behavioural objectives for the problem solving phase of their curriculum. They were assigned for 11 weeks to various hospital settings that differed in the presence or absence of structured classes, the expertise of the teaching staff, the amount of instruction time and the types of learning experiences. At the end of that time, the students took the same examination to measure attainment of the objectives. The only variable that was associated with significantly different examination scores was presence or absence of structured classes.", "contents": "The attainment of specified objectives by medical students in different learning environments. Medical students were provided with behavioural objectives for the problem solving phase of their curriculum. They were assigned for 11 weeks to various hospital settings that differed in the presence or absence of structured classes, the expertise of the teaching staff, the amount of instruction time and the types of learning experiences. At the end of that time, the students took the same examination to measure attainment of the objectives. The only variable that was associated with significantly different examination scores was presence or absence of structured classes."} {"id": "PMID:1268124", "title": "The use of computerized patient management problems in a certifying examination.", "content": "The 1974 paediatric certification process of the Royal College of Physicians and Surgeons of Canada included four CPMPs, in addition to the conventional MCQs and orals. The CPMP's were successfully administered to 160 candidates in eight cities across Canada on the same day. The examination was judged by the candidates to be a better test of clinical skill than MCQs. The CPMP examination did not penalize French-speaking candidates, was economically feasible, and a good security risk. Correlations between MCQ, orals and CPMPs, indicated that each examination measured some aspects of paediatric competence not tested by the others.", "contents": "The use of computerized patient management problems in a certifying examination. The 1974 paediatric certification process of the Royal College of Physicians and Surgeons of Canada included four CPMPs, in addition to the conventional MCQs and orals. The CPMP's were successfully administered to 160 candidates in eight cities across Canada on the same day. The examination was judged by the candidates to be a better test of clinical skill than MCQs. The CPMP examination did not penalize French-speaking candidates, was economically feasible, and a good security risk. Correlations between MCQ, orals and CPMPs, indicated that each examination measured some aspects of paediatric competence not tested by the others."} {"id": "PMID:1268125", "title": "Teaching psychologists to teach psychology: the improvement of teaching skills in health service professions.", "content": "The need to improve the quality of teaching received by health service professionals is apparent from several recent reports. A short course of approximately 10 class hours is described, as used to train clinical psychologists in teaching method, with particular reference to teaching nurses. Problems of lecture content and preparation are discussed, emphasis is laid on the use of varied and active teaching methods, and the need for feedback from the students. The course was well received by students, and acceptable into an already crowded curriculum.", "contents": "Teaching psychologists to teach psychology: the improvement of teaching skills in health service professions. The need to improve the quality of teaching received by health service professionals is apparent from several recent reports. A short course of approximately 10 class hours is described, as used to train clinical psychologists in teaching method, with particular reference to teaching nurses. Problems of lecture content and preparation are discussed, emphasis is laid on the use of varied and active teaching methods, and the need for feedback from the students. The course was well received by students, and acceptable into an already crowded curriculum."} {"id": "PMID:1268126", "title": "Teaching the teachers.", "content": "This and the following two papers describe historically the development of courses for general practice teachers in Manchester from 1966. The first paper describes the early attempts to fashion an appropriate course, discusses the content of such courses and the methods used. The second and third papers then discuss a course on non-directive behavioural counselling as an educational tool and describe the evolution of a cycle of four courses, each dealing with separate aspects of teaching. The emphasis throughout is on person to person teaching, it being considered that this is the commonest teaching/learning situation in general practice. The second part of the first paper goes on to discuss the logistic needs for the preparation and maintenance of teachers in general practice.", "contents": "Teaching the teachers. This and the following two papers describe historically the development of courses for general practice teachers in Manchester from 1966. The first paper describes the early attempts to fashion an appropriate course, discusses the content of such courses and the methods used. The second and third papers then discuss a course on non-directive behavioural counselling as an educational tool and describe the evolution of a cycle of four courses, each dealing with separate aspects of teaching. The emphasis throughout is on person to person teaching, it being considered that this is the commonest teaching/learning situation in general practice. The second part of the first paper goes on to discuss the logistic needs for the preparation and maintenance of teachers in general practice."} {"id": "PMID:1268127", "title": "A teaching methods course in Manchester for general practitioner teachers.", "content": "A teaching-methods course for general practitioner teachers is described. It lasts for 20 days, split into four 5-day residential sections held at intervals of 6 months. The sections are respectively entitled person-to-person teaching, small group teaching, teaching behaviour, and a micro-training laboratory. They recur in a cycle. The approach in each section is that of experimental learning--necessarily, since an aim of the course is to enable the members to apply the same approach in their own teaching. The methods of three of the sections are given in some detail. The person-to-person teaching section, concerned mainly with the learning of counselling skills, is dealt with fully by Long et al. (1976), and is here presented very briefly. The limited evaluation and assessment procedure, and their results, are offered together with certain general conclusions.", "contents": "A teaching methods course in Manchester for general practitioner teachers. A teaching-methods course for general practitioner teachers is described. It lasts for 20 days, split into four 5-day residential sections held at intervals of 6 months. The sections are respectively entitled person-to-person teaching, small group teaching, teaching behaviour, and a micro-training laboratory. They recur in a cycle. The approach in each section is that of experimental learning--necessarily, since an aim of the course is to enable the members to apply the same approach in their own teaching. The methods of three of the sections are given in some detail. The person-to-person teaching section, concerned mainly with the learning of counselling skills, is dealt with fully by Long et al. (1976), and is here presented very briefly. The limited evaluation and assessment procedure, and their results, are offered together with certain general conclusions."} {"id": "PMID:1268128", "title": "Assessment by dual examination of the teaching of respiratory diseases.", "content": "This study was designed to test the effectiveness of the teaching programme in respiratory diseases. It showed that those students who did not have a clinical attachment in the speciality were at a disadvantage when compared with their fellows provided with a clinical attachment.", "contents": "Assessment by dual examination of the teaching of respiratory diseases. This study was designed to test the effectiveness of the teaching programme in respiratory diseases. It showed that those students who did not have a clinical attachment in the speciality were at a disadvantage when compared with their fellows provided with a clinical attachment."} {"id": "PMID:1268133", "title": "Cigarette smoking and fetal breathing movements.", "content": "Cigarette smoking caused a reduction in the incidence of fetal breathing movements in normal and abnormal pregnancies. The size of the reduction varied, being greatest in small-for-dates pregnancies and pregnancies complicated by fetal distress in labour and least in pre-eclamptic pregnancies. The fall in the amount of fetal breathing movements was significantly related to the rise in maternal plasma nicotine after smoking but was unrelated to the rise in barboxyhaemoglobin. Smoking non-nicotine (herbal) cigarettes produced increases in carboxyhaemoglobin concentrations similar to those observed after smoking tobacco cigarettes, and was not associated with a fall in the incidence of fetal breathing movements. Chewing gum containing nicotine produced rises in plasma nicotine concentration similar to those observed after smoking tobacco cigarettes and was associated with a significant reduction in the incidence of fetal breathing movements. Hence nicotine appeared to be the factor in cigarette smoke responsible for the reduction in the incidence of fetal breathing movements. Nicotine was present in the cord blood of infants whose mothers smoked. The possible mechanism by which nicotine caused a reduction in the incidence of fetal breathing movements and its possible relevance to the detrimental effects of smoking on the fetus are considered.", "contents": "Cigarette smoking and fetal breathing movements. Cigarette smoking caused a reduction in the incidence of fetal breathing movements in normal and abnormal pregnancies. The size of the reduction varied, being greatest in small-for-dates pregnancies and pregnancies complicated by fetal distress in labour and least in pre-eclamptic pregnancies. The fall in the amount of fetal breathing movements was significantly related to the rise in maternal plasma nicotine after smoking but was unrelated to the rise in barboxyhaemoglobin. Smoking non-nicotine (herbal) cigarettes produced increases in carboxyhaemoglobin concentrations similar to those observed after smoking tobacco cigarettes, and was not associated with a fall in the incidence of fetal breathing movements. Chewing gum containing nicotine produced rises in plasma nicotine concentration similar to those observed after smoking tobacco cigarettes and was associated with a significant reduction in the incidence of fetal breathing movements. Hence nicotine appeared to be the factor in cigarette smoke responsible for the reduction in the incidence of fetal breathing movements. Nicotine was present in the cord blood of infants whose mothers smoked. The possible mechanism by which nicotine caused a reduction in the incidence of fetal breathing movements and its possible relevance to the detrimental effects of smoking on the fetus are considered."} {"id": "PMID:1268134", "title": "Dolichocephaly--a source of error in serial cephalometry.", "content": "Two patients are presented in whom ultrasonic cephalometry suggested intrauterine fetal growth retardation. The respective newborn infants were normally grown and had dolichocephaly with a normal head circumference. Dolichocephaly should be considered when cephalometry alone suggests a diagnosis of placental insufficiency.", "contents": "Dolichocephaly--a source of error in serial cephalometry. Two patients are presented in whom ultrasonic cephalometry suggested intrauterine fetal growth retardation. The respective newborn infants were normally grown and had dolichocephaly with a normal head circumference. Dolichocephaly should be considered when cephalometry alone suggests a diagnosis of placental insufficiency."} {"id": "PMID:1268135", "title": "The relation between ease of forceps delivery and speed of cervical dilatation.", "content": "An attempt has been made to predict a difficult forceps delivery. The duration of the 7 to 10 cm cervical dilatation interval was measured from the completed cervimetric chart in 952 consecutive patients who delivered spontaneously between December 1973 and September 1974. The 7 to 10 cm cervical dilatation intervals of this group were compared with those of 378 consecutive patients in whom forceps were applied with the fetal head in the occipito-anterior position and 83 consecutive patients where Kielland's forceps rotation from the occipito-tranverse or occipito-posterior position was performed. The forceps deliveries were graded as 'easy', 'moderately difficult', or 'difficult'. In only 5% of the spontaneous delivery group did the 7 to 10 cm cervical dilatation interval exceed two hours. In the occipito-anterior and Kielland's forceps groups an 'easy' delivery could be expected if the 7 to 10 cm cervical dilatation interval was less than two hours. The greater this interval increased beyond two hours, the greater was the proportion of 'moderately difficult' and 'difficult' forceps deliveries.", "contents": "The relation between ease of forceps delivery and speed of cervical dilatation. An attempt has been made to predict a difficult forceps delivery. The duration of the 7 to 10 cm cervical dilatation interval was measured from the completed cervimetric chart in 952 consecutive patients who delivered spontaneously between December 1973 and September 1974. The 7 to 10 cm cervical dilatation intervals of this group were compared with those of 378 consecutive patients in whom forceps were applied with the fetal head in the occipito-anterior position and 83 consecutive patients where Kielland's forceps rotation from the occipito-tranverse or occipito-posterior position was performed. The forceps deliveries were graded as 'easy', 'moderately difficult', or 'difficult'. In only 5% of the spontaneous delivery group did the 7 to 10 cm cervical dilatation interval exceed two hours. In the occipito-anterior and Kielland's forceps groups an 'easy' delivery could be expected if the 7 to 10 cm cervical dilatation interval was less than two hours. The greater this interval increased beyond two hours, the greater was the proportion of 'moderately difficult' and 'difficult' forceps deliveries."} {"id": "PMID:1268136", "title": "Platelets and intrauterine growth retardation in pre-eclampsia.", "content": "In pre-eclampsia, but not essential hypertension of pregnancy, reduced maternal levels of circulating platelets were found to correlate with intrauterine growth retardation. This suggests that disseminated intravascular coagulation and fibrin deposition contribute to the placental damage of pre-eclampsia.", "contents": "Platelets and intrauterine growth retardation in pre-eclampsia. In pre-eclampsia, but not essential hypertension of pregnancy, reduced maternal levels of circulating platelets were found to correlate with intrauterine growth retardation. This suggests that disseminated intravascular coagulation and fibrin deposition contribute to the placental damage of pre-eclampsia."} {"id": "PMID:1268137", "title": "Circulating levels of fibrin/fibrinogen degradation fragment E measured by radioimmunoassay in pre-eclampsia.", "content": "Levels of fibrin/fibrinogen degradation products have been measured by a sensitive and specific radioimmunoassay in pregnancies associated with pre-eclampsia or essential hypertension. The incidence of elevated levels was low (2-4%) in mild and moderate cases, and rather higher (30%) in severe cases. In no patients were the levels consistently elevated prior to the onset of clinical signs.", "contents": "Circulating levels of fibrin/fibrinogen degradation fragment E measured by radioimmunoassay in pre-eclampsia. Levels of fibrin/fibrinogen degradation products have been measured by a sensitive and specific radioimmunoassay in pregnancies associated with pre-eclampsia or essential hypertension. The incidence of elevated levels was low (2-4%) in mild and moderate cases, and rather higher (30%) in severe cases. In no patients were the levels consistently elevated prior to the onset of clinical signs."} {"id": "PMID:1268138", "title": "Studies on the effect of maternal pre-eclamptic toxaemia on placental weight and on head size and birth weight of the newborn.", "content": "The influence of pre-eclamptic toxaemia (PET) on head size and birth weight of newborn infants and placental weight was studied in single live births after 35 to 42 weeks gestation from mothers with or without toxaemia. There were no significant differences in the distribution of mean birth weight, head size, placental weight, head size/birth weight ratio or placental weight/birth weight ratio between the toxaemic and non-toxaemic groups. There were significant differences between toxaemic and non-toxaemic mothers as regards parity, height and smoking habits. Since such maternal characteristics influence birth weights a correction was applied for them. The influence of maternal mid-term weight and sex of the infants was also taken into account. No significant differences in corrected birth weights, between toxaemic and non-toxaemic groups were detected on further analysis. It is suggested that the present obstetric management has prevented the retarding effect of pre-eclamptic toxaemia on fetal and placental growth by reducing the severity and duration of the illness.", "contents": "Studies on the effect of maternal pre-eclamptic toxaemia on placental weight and on head size and birth weight of the newborn. The influence of pre-eclamptic toxaemia (PET) on head size and birth weight of newborn infants and placental weight was studied in single live births after 35 to 42 weeks gestation from mothers with or without toxaemia. There were no significant differences in the distribution of mean birth weight, head size, placental weight, head size/birth weight ratio or placental weight/birth weight ratio between the toxaemic and non-toxaemic groups. There were significant differences between toxaemic and non-toxaemic mothers as regards parity, height and smoking habits. Since such maternal characteristics influence birth weights a correction was applied for them. The influence of maternal mid-term weight and sex of the infants was also taken into account. No significant differences in corrected birth weights, between toxaemic and non-toxaemic groups were detected on further analysis. It is suggested that the present obstetric management has prevented the retarding effect of pre-eclamptic toxaemia on fetal and placental growth by reducing the severity and duration of the illness."} {"id": "PMID:1268139", "title": "Plasminogen activators in the endometrium of women using intrauterine contraceptive devices.", "content": "Plasminogen activators in the endometrium before and after the insertion of an intrauterine contraceptive device (IUCD) were studied; an increase in the concentration was found following IUCD insertion in 16 of the 20 women. This change will enhance endometrial fibrinolysis and may explain the increased menstrual bleeding which usually follows insertion of an IUCD.", "contents": "Plasminogen activators in the endometrium of women using intrauterine contraceptive devices. Plasminogen activators in the endometrium before and after the insertion of an intrauterine contraceptive device (IUCD) were studied; an increase in the concentration was found following IUCD insertion in 16 of the 20 women. This change will enhance endometrial fibrinolysis and may explain the increased menstrual bleeding which usually follows insertion of an IUCD."} {"id": "PMID:1268140", "title": "Practolol peritonitis presenting as a pelvic mass.", "content": "A case of sclerosing fibro-peritonitis occurring as a result of practolol therapy is presented. This may occur months after cessation of the practolol because of other side effects and may present to the gynaecologists as a pelvic mass.", "contents": "Practolol peritonitis presenting as a pelvic mass. A case of sclerosing fibro-peritonitis occurring as a result of practolol therapy is presented. This may occur months after cessation of the practolol because of other side effects and may present to the gynaecologists as a pelvic mass."} {"id": "PMID:1268141", "title": "Studies in the involvement of prostaglandins in uterine symptomatology and pathology.", "content": "The concentrations of prostaglandin E2 and F2alpha were measured by radioimmunoassay in samples of endometrial tissue from 155 women. The results showed that the concentration of prostaglandins E2 (ng/100 mg of wet tissue; mean +/- SD) in tissue from apparently healthy women with regular menstrual cycles was 79-3 +/- 9-9 during the menstrual period. The level in the proliferative and early secretory phases fell to 11-8 +/- 4-0 and 13-3 +/- 8-3 respectively. During the late secretory phase there was a significant increase to 20-1 +/- 10-8. The corresponding values from patients with fibromyomata and without menorrhagia were similar. However, the concentration in tissue from patients with fibromyomata and menorrhagia was significantly higher (63-9 +/- 17-9) during the secretory phase of the uterine cycle. In addition, the amount was significantly higher in the groups with dysmenorrhoea (19-0 +/- 4-5 proliferative; 68-0 +/-18-15 secretory) and irregular uterine bleeding (78-3 +/- 59-0 proliferative; 87-4 +/- 64-9 secretory). The mean concentration was higher in cases of endometriosis, and significantly elevated in endometrial carcinoma. The results for prostaglandin F2alpha showed a similar pattern, but the changes were less marked in patients with irregular dysfunctional bleeding. The findings are discussed.", "contents": "Studies in the involvement of prostaglandins in uterine symptomatology and pathology. The concentrations of prostaglandin E2 and F2alpha were measured by radioimmunoassay in samples of endometrial tissue from 155 women. The results showed that the concentration of prostaglandins E2 (ng/100 mg of wet tissue; mean +/- SD) in tissue from apparently healthy women with regular menstrual cycles was 79-3 +/- 9-9 during the menstrual period. The level in the proliferative and early secretory phases fell to 11-8 +/- 4-0 and 13-3 +/- 8-3 respectively. During the late secretory phase there was a significant increase to 20-1 +/- 10-8. The corresponding values from patients with fibromyomata and without menorrhagia were similar. However, the concentration in tissue from patients with fibromyomata and menorrhagia was significantly higher (63-9 +/- 17-9) during the secretory phase of the uterine cycle. In addition, the amount was significantly higher in the groups with dysmenorrhoea (19-0 +/- 4-5 proliferative; 68-0 +/-18-15 secretory) and irregular uterine bleeding (78-3 +/- 59-0 proliferative; 87-4 +/- 64-9 secretory). The mean concentration was higher in cases of endometriosis, and significantly elevated in endometrial carcinoma. The results for prostaglandin F2alpha showed a similar pattern, but the changes were less marked in patients with irregular dysfunctional bleeding. The findings are discussed."} {"id": "PMID:1268142", "title": "Factors associated with spontaneous pre-term birth.", "content": "Factors associated with spontaneous pre-term birth in 283 singleton pregnancies were compared with those present in a total population of 16 994 women at risk studied in the First British Perinatal Mortality Survey. It was shown that the risk of spontaneous pre-term birth was related to low maternal age, low maternal weight, maternal smoking, low social class, illegitimacy, threatened abortion, and a previous history of antepartum haemorrhage, perinatal loss, or low birth weight livebirths.", "contents": "Factors associated with spontaneous pre-term birth. Factors associated with spontaneous pre-term birth in 283 singleton pregnancies were compared with those present in a total population of 16 994 women at risk studied in the First British Perinatal Mortality Survey. It was shown that the risk of spontaneous pre-term birth was related to low maternal age, low maternal weight, maternal smoking, low social class, illegitimacy, threatened abortion, and a previous history of antepartum haemorrhage, perinatal loss, or low birth weight livebirths."} {"id": "PMID:1268143", "title": "Antenatal identification of women at high risk of spontaneous pre-term birth.", "content": "A means of assessing the risk of a spontaneous pre-term birth in any individual woman presenting at the antenatal clinic is described. A composite score can be obtained by the multiplication of relative risks for various factors. The effectiveness of the method is discussed.", "contents": "Antenatal identification of women at high risk of spontaneous pre-term birth. A means of assessing the risk of a spontaneous pre-term birth in any individual woman presenting at the antenatal clinic is described. A composite score can be obtained by the multiplication of relative risks for various factors. The effectiveness of the method is discussed."} {"id": "PMID:1268144", "title": "Coagulation and fibrinolysis in pregnancies complicated by fetal growth retardation.", "content": "Saline extracts were made from portions of 17 normal placentae and from 8 placentae from pregnancies complicated by fetal growth retardation, but not hypertension. The ability of these extracts to inhibit urokinase-induced fibrinolysis was measured using a fibrin plate technique. Placental extracts from pregnancies complicated by fetal growth retardation exhibited greater inhibition of urokinase-induced fibrinolysis. There was no evidence of disseminated intravascular coagulation in these patients, but certain coagulation factors in the peripheral blood were raised.", "contents": "Coagulation and fibrinolysis in pregnancies complicated by fetal growth retardation. Saline extracts were made from portions of 17 normal placentae and from 8 placentae from pregnancies complicated by fetal growth retardation, but not hypertension. The ability of these extracts to inhibit urokinase-induced fibrinolysis was measured using a fibrin plate technique. Placental extracts from pregnancies complicated by fetal growth retardation exhibited greater inhibition of urokinase-induced fibrinolysis. There was no evidence of disseminated intravascular coagulation in these patients, but certain coagulation factors in the peripheral blood were raised."} {"id": "PMID:1268145", "title": "Longitudinal study of the free cortisol index in pregnancy.", "content": "Total plasma cortisol, the 'cortisol resin uptake ratio' (cortisol RUR), and 'free cortisol index' (FCI) were estimated in 23 pregnant women from 12 weeks to term and at six weeks post partum. Total plasma cortisol rose continually throughout pregnancy; the cortisol RUR rose up to 20 to 23 weeks and then fell slowly and the FCI also rose although more slowly than the total cortisol. All parameters fell to non-pregnant levels at six weeks post partum. It is confirmed that a true rise in metabolically active cortisol occurs during pregnancy.", "contents": "Longitudinal study of the free cortisol index in pregnancy. Total plasma cortisol, the 'cortisol resin uptake ratio' (cortisol RUR), and 'free cortisol index' (FCI) were estimated in 23 pregnant women from 12 weeks to term and at six weeks post partum. Total plasma cortisol rose continually throughout pregnancy; the cortisol RUR rose up to 20 to 23 weeks and then fell slowly and the FCI also rose although more slowly than the total cortisol. All parameters fell to non-pregnant levels at six weeks post partum. It is confirmed that a true rise in metabolically active cortisol occurs during pregnancy."} {"id": "PMID:1268146", "title": "Iron stores in pregnant patients with anaemia and haemoglobin S.", "content": "Marrow aspiration in 22 pregnant women with haemoglobin S revealed a high incidence of iron deficiency. Eighteen patients showed depleted iron stores while depots were adequate in four patients. The practice of denying iron to pregnant women with haemoglobinopathies is not recommended; nor is the use of prophylactic iron in all patients with sickle cell disease or trait advised. It is suggested that it is better to diagnose and treat the iron deficiency specifically.", "contents": "Iron stores in pregnant patients with anaemia and haemoglobin S. Marrow aspiration in 22 pregnant women with haemoglobin S revealed a high incidence of iron deficiency. Eighteen patients showed depleted iron stores while depots were adequate in four patients. The practice of denying iron to pregnant women with haemoglobinopathies is not recommended; nor is the use of prophylactic iron in all patients with sickle cell disease or trait advised. It is suggested that it is better to diagnose and treat the iron deficiency specifically."} {"id": "PMID:1268147", "title": "Tissue oxygenation and red cell 2,3-diphsophoglycerate in normal and abnormal pregnancy.", "content": "Maternal tissue oxygenation was reflected by the level of red cell, 2,3-diphosphoglycerate (DPG) was measured before, during and after normal pregnancy. Following an initial fall at the beginning of pregnancy there was a significant rise in the mean level of DPG during pregnancy with an abrupt fall in the puerperium. The mean red cell DPG level in the third trimester of pregnancies complicated by pre-eclampsia and diabetes was not statistically different from the normal but the mean value of all pregnancies in which the fetus was stillborn or growth retarded was significantly lower (p less than 0-001). The possible mechanism of the changes in normal and abnormal pregnancy is discussed and it is suggested that the measurement of red cell DPG in the third trimester of pregnancy may prove to be a useful parameter of placental oxygenation.", "contents": "Tissue oxygenation and red cell 2,3-diphsophoglycerate in normal and abnormal pregnancy. Maternal tissue oxygenation was reflected by the level of red cell, 2,3-diphosphoglycerate (DPG) was measured before, during and after normal pregnancy. Following an initial fall at the beginning of pregnancy there was a significant rise in the mean level of DPG during pregnancy with an abrupt fall in the puerperium. The mean red cell DPG level in the third trimester of pregnancies complicated by pre-eclampsia and diabetes was not statistically different from the normal but the mean value of all pregnancies in which the fetus was stillborn or growth retarded was significantly lower (p less than 0-001). The possible mechanism of the changes in normal and abnormal pregnancy is discussed and it is suggested that the measurement of red cell DPG in the third trimester of pregnancy may prove to be a useful parameter of placental oxygenation."} {"id": "PMID:1268148", "title": "Individual free fatty acids in amniotic fluid and in plasma of pregnant women.", "content": "Individual free fatty acids (FFA) were measured in 77 amniotic fluid samples and in 57 maternal plasma samples. Gestational age ranged from 16 to 40 weeks. Amniotic fluid FFA decreased from 20-4 +/- 6-0 mumol/l in the second trimester to 17-0 +/- 6-0 mumol/l in the last six weeks of pregnancy. This was almost entirely accounted for by a decrease in the concentration of free stearic acid, while oleic acid increased slightly. No correlation between amniotic fluid FFA and maternal plasma FFA was found in samples obtained on the same day. It is suggested that amniotic fluid FFA may partly derive from renal excretion by the fetus.", "contents": "Individual free fatty acids in amniotic fluid and in plasma of pregnant women. Individual free fatty acids (FFA) were measured in 77 amniotic fluid samples and in 57 maternal plasma samples. Gestational age ranged from 16 to 40 weeks. Amniotic fluid FFA decreased from 20-4 +/- 6-0 mumol/l in the second trimester to 17-0 +/- 6-0 mumol/l in the last six weeks of pregnancy. This was almost entirely accounted for by a decrease in the concentration of free stearic acid, while oleic acid increased slightly. No correlation between amniotic fluid FFA and maternal plasma FFA was found in samples obtained on the same day. It is suggested that amniotic fluid FFA may partly derive from renal excretion by the fetus."} {"id": "PMID:1268149", "title": "The influence of pyridoxine on prolactin secretion and milk production in women.", "content": "Pyridoxine treatment did not inhibit milk secretion in 14 puerperal women. In contrast, bromocriptine was antilactogenic. Pyridoxine appeared not to suppress prolactin secretion.", "contents": "The influence of pyridoxine on prolactin secretion and milk production in women. Pyridoxine treatment did not inhibit milk secretion in 14 puerperal women. In contrast, bromocriptine was antilactogenic. Pyridoxine appeared not to suppress prolactin secretion."} {"id": "PMID:1268150", "title": "Puerperal ultrasonic hysterography in the diagnosis of congenital uterine malformations.", "content": "Puerperal ultrasonic hysterography has been found to be a safe and simple technique. It is suggested as a screening procedure prior to radiological hysterography in patients whose recent reproductive performance suggests a diagnosis of congenital malformation of the uterus.", "contents": "Puerperal ultrasonic hysterography in the diagnosis of congenital uterine malformations. Puerperal ultrasonic hysterography has been found to be a safe and simple technique. It is suggested as a screening procedure prior to radiological hysterography in patients whose recent reproductive performance suggests a diagnosis of congenital malformation of the uterus."} {"id": "PMID:1268151", "title": "Tumour associated immunity and immunocompetence in ovarian cancer.", "content": "Cell-free extracts of autologous ovarian cancer cells evoked a delayed hypersensitivity response (DHR) in skin in four out of six patients in remission from disease and none of seven patients in relapse. These initial results appear to be consistent with in vitro blastogenic assay using the same autologous extracts. To assess whether diminished tumour-associated immunity was due to impaired cell-mediated immunocompetence, blastogenic responses to purified protein derivative of tuberculin (PPD), a secondary recall antigen, and phytohaemagglutinin (PHA) were assessed. Impaired responses to PHA were seen in the relapse group of patients, but responses to PPD did not appear to be impaired in this group.", "contents": "Tumour associated immunity and immunocompetence in ovarian cancer. Cell-free extracts of autologous ovarian cancer cells evoked a delayed hypersensitivity response (DHR) in skin in four out of six patients in remission from disease and none of seven patients in relapse. These initial results appear to be consistent with in vitro blastogenic assay using the same autologous extracts. To assess whether diminished tumour-associated immunity was due to impaired cell-mediated immunocompetence, blastogenic responses to purified protein derivative of tuberculin (PPD), a secondary recall antigen, and phytohaemagglutinin (PHA) were assessed. Impaired responses to PHA were seen in the relapse group of patients, but responses to PPD did not appear to be impaired in this group."} {"id": "PMID:1268152", "title": "Lipogranuloma of the uterine parametrium.", "content": "A case of lipogranuloma of the uterine parametrium is described. The granuloma may have developed following injury to fat cells after a cone biopsy of the cervix or may have resulted from a reaction to paraffin.", "contents": "Lipogranuloma of the uterine parametrium. A case of lipogranuloma of the uterine parametrium is described. The granuloma may have developed following injury to fat cells after a cone biopsy of the cervix or may have resulted from a reaction to paraffin."} {"id": "PMID:1268156", "title": "Morphology of posterior segment lesions of the eye in patients with onchocerciasis.", "content": "Posterior segment ocular lesions were examined in 244 selected patients with onchocerciasis from the Sudan-savanna and rain-forest areas of the United Cameroon Republic. Fluorescein fundus angiography was performed on 210 cases. As a result of this study the following conclusions were drawn: 1. The heterogeneity of single lesions, and the occurrence of different types of lesion in a single eye or two eyes, prevented subdivision of the disease into distinct forms and suggested that inflammation alone was responsible for fundus lesions in onchocerciasis. 2. Optic nerve disease, alone or in the presence of choroido-retinal changes, was responsible for a large proportion of the blindness due to posterior segment lesions in onchocerciasis (87.6 per cent in this series).", "contents": "Morphology of posterior segment lesions of the eye in patients with onchocerciasis. Posterior segment ocular lesions were examined in 244 selected patients with onchocerciasis from the Sudan-savanna and rain-forest areas of the United Cameroon Republic. Fluorescein fundus angiography was performed on 210 cases. As a result of this study the following conclusions were drawn: 1. The heterogeneity of single lesions, and the occurrence of different types of lesion in a single eye or two eyes, prevented subdivision of the disease into distinct forms and suggested that inflammation alone was responsible for fundus lesions in onchocerciasis. 2. Optic nerve disease, alone or in the presence of choroido-retinal changes, was responsible for a large proportion of the blindness due to posterior segment lesions in onchocerciasis (87.6 per cent in this series)."} {"id": "PMID:1268157", "title": "Acquired arterial macroaneurysms of the retina.", "content": "Fifteen patients with acquired arterial macroaneurysms of the retina, and an additional woman patient with some 18 aneurysms of the temporal retinal arterial tree of one eye, are described. Acquired aneurysms occur in patients in their sixth decade and older, are usually unilateral, and occur on the major arterial branches posterior to the equator. Customarily only one or two aneurysms are present. Most patients have a history of poorly controlled systemic hypertension or a raised blood pressure at the time of discovery of the macroaneurysm. Focal embolic damage to arterial walls should be considered in the investigation of these patients. In patients with decreased vision from macular oedema and circinate retinopathy, photocoagulation of the macroaneurysm may hasten the improvement in visual acuity.", "contents": "Acquired arterial macroaneurysms of the retina. Fifteen patients with acquired arterial macroaneurysms of the retina, and an additional woman patient with some 18 aneurysms of the temporal retinal arterial tree of one eye, are described. Acquired aneurysms occur in patients in their sixth decade and older, are usually unilateral, and occur on the major arterial branches posterior to the equator. Customarily only one or two aneurysms are present. Most patients have a history of poorly controlled systemic hypertension or a raised blood pressure at the time of discovery of the macroaneurysm. Focal embolic damage to arterial walls should be considered in the investigation of these patients. In patients with decreased vision from macular oedema and circinate retinopathy, photocoagulation of the macroaneurysm may hasten the improvement in visual acuity."} {"id": "PMID:1268158", "title": "Angioid streaks and sickle haemoglobinopathies.", "content": "Five patients had angioid streaks associated with sickle cell haemoglobinopathy. Other diseases associated with angioid streaks were ruled out, as was elastic tissue degenegation in sickle cell patients. After studying over 350 patients, we believe the incidence of angioid streaks in sickle cell disease to be between 1 and 2 per cent.", "contents": "Angioid streaks and sickle haemoglobinopathies. Five patients had angioid streaks associated with sickle cell haemoglobinopathy. Other diseases associated with angioid streaks were ruled out, as was elastic tissue degenegation in sickle cell patients. After studying over 350 patients, we believe the incidence of angioid streaks in sickle cell disease to be between 1 and 2 per cent."} {"id": "PMID:1268159", "title": "Reticular tapeto-retinal dystrophy. As a possible late stage of Sj\u00f6gren's reticular dystrophy.", "content": "Findings from two patients with a reticular tapetoretinal dystrophy strongly suggested advanced stages of Sj\u00f6gren's reticular dystrophy. These observations emphasize that, although initially a benign disease, advanced stages of Sj\u00f6rgren's dystrophy may eventually manifest diffuse photoreceptor and retinal pigment epithelial disease.", "contents": "Reticular tapeto-retinal dystrophy. As a possible late stage of Sj\u00f6gren's reticular dystrophy. Findings from two patients with a reticular tapetoretinal dystrophy strongly suggested advanced stages of Sj\u00f6gren's reticular dystrophy. These observations emphasize that, although initially a benign disease, advanced stages of Sj\u00f6rgren's dystrophy may eventually manifest diffuse photoreceptor and retinal pigment epithelial disease."} {"id": "PMID:1268160", "title": "Vitreous opacities in primary amyloid disease. A clinical, histochemical, and ultrastructural report.", "content": "Three patients who initially presented to the ophthalmologist with a history of gradual deterioration of visual acuity showed, on biomicroscopic examination, a linear meshwork of opacities in the vitreous attached to the posterior surface of the lens in the form of pseudopodia lentis. Amyloidosis of the vitreous associated with systemic amyloid disease was diagnosed because of the characteristic nature of the opacities. This was confirmed initially in two of the cases by light and electron microscopical examination of a biopsy of the clinically normal conjunctiva, subsequently by systemic investigations, and finally, by direct histochemical and elecron microscopical examination of the vitreous which became available after vitrectomy in all three cases. It was not possible to examine other members of the families. The relevant literature on vitreous amyloidosis is reviewed in relation to our own findings and the importance of a diagnostic conjunctival biopsy is emphasized. This paper is the first British report on primary vitreous amyloidosis. The pathogenesis of vitreous amyloid opacities is discussed in the light of current concepts of amyloidosis. Since the vitreous opacities due to amyloid deposits appear to be one of the manifestations of systemic amyloid disease, surgical removal of the opacities by vitrectomy may not produce longlasting results. Moveover, in contemplating surgical treatment the ophthalmologist should bear in mind the poor prognosis of systemic amyloidosis.", "contents": "Vitreous opacities in primary amyloid disease. A clinical, histochemical, and ultrastructural report. Three patients who initially presented to the ophthalmologist with a history of gradual deterioration of visual acuity showed, on biomicroscopic examination, a linear meshwork of opacities in the vitreous attached to the posterior surface of the lens in the form of pseudopodia lentis. Amyloidosis of the vitreous associated with systemic amyloid disease was diagnosed because of the characteristic nature of the opacities. This was confirmed initially in two of the cases by light and electron microscopical examination of a biopsy of the clinically normal conjunctiva, subsequently by systemic investigations, and finally, by direct histochemical and elecron microscopical examination of the vitreous which became available after vitrectomy in all three cases. It was not possible to examine other members of the families. The relevant literature on vitreous amyloidosis is reviewed in relation to our own findings and the importance of a diagnostic conjunctival biopsy is emphasized. This paper is the first British report on primary vitreous amyloidosis. The pathogenesis of vitreous amyloid opacities is discussed in the light of current concepts of amyloidosis. Since the vitreous opacities due to amyloid deposits appear to be one of the manifestations of systemic amyloid disease, surgical removal of the opacities by vitrectomy may not produce longlasting results. Moveover, in contemplating surgical treatment the ophthalmologist should bear in mind the poor prognosis of systemic amyloidosis."} {"id": "PMID:1268161", "title": "Optic neuritis in the Landry-Guillain-Barr\u00e9-Strohl syndrome.", "content": "A patient with typical Landry-Guillain-Barr\u00e9-Strohl syndrome (LG-BS) developed bilateral optic neuritis. Laboratory studies showed hypersensitivity to both central and peripheral nervous tissue myelin. The occurrence of optic neuritis is presumably due to autohypersensitivity to central nervous tissue myelin. The initial lesions of the LG-BS syndrome in the peripheral nerves might have liberated sequestered antigens that cross-reacted with central nervous system myelin.", "contents": "Optic neuritis in the Landry-Guillain-Barr\u00e9-Strohl syndrome. A patient with typical Landry-Guillain-Barr\u00e9-Strohl syndrome (LG-BS) developed bilateral optic neuritis. Laboratory studies showed hypersensitivity to both central and peripheral nervous tissue myelin. The occurrence of optic neuritis is presumably due to autohypersensitivity to central nervous tissue myelin. The initial lesions of the LG-BS syndrome in the peripheral nerves might have liberated sequestered antigens that cross-reacted with central nervous system myelin."} {"id": "PMID:1268162", "title": "Uhthoff's syndrome.", "content": "A total of 125 patients with a previous episode of optic neuritis was followed to assess the subsequent prevalence of transient visual blurring. 32.8 per cent developed this symptom and the precipitating factors were identified. No correlations were found between the development of the symptom and the parameters of optic nerve function studied.", "contents": "Uhthoff's syndrome. A total of 125 patients with a previous episode of optic neuritis was followed to assess the subsequent prevalence of transient visual blurring. 32.8 per cent developed this symptom and the precipitating factors were identified. No correlations were found between the development of the symptom and the parameters of optic nerve function studied."} {"id": "PMID:1268164", "title": "Quantitative tear lysozyme assay in units of activity per microlitre.", "content": "An accurate method of assaying the tear lysozyme concentration in units of activity/mul has been developed. Normal physiological levels which vary with age have been determined. It has been demonstrated that measurement of the volume of tear fluid collected and assay with a calibrated standard are essential for the accurate determination of the precise concentration of lysozyme in the tear fluid. Tear lyozyme concentration can be used as an index of lacrimal gland function, and in the diagnosis of the sicca syndrome and associated conditions. We believe that this method of tear lyozyme assay has important applications in drug toxicity states in humans (for example, practolol toxicity) and also in animal drug toxicity studies.", "contents": "Quantitative tear lysozyme assay in units of activity per microlitre. An accurate method of assaying the tear lysozyme concentration in units of activity/mul has been developed. Normal physiological levels which vary with age have been determined. It has been demonstrated that measurement of the volume of tear fluid collected and assay with a calibrated standard are essential for the accurate determination of the precise concentration of lysozyme in the tear fluid. Tear lyozyme concentration can be used as an index of lacrimal gland function, and in the diagnosis of the sicca syndrome and associated conditions. We believe that this method of tear lyozyme assay has important applications in drug toxicity states in humans (for example, practolol toxicity) and also in animal drug toxicity studies."} {"id": "PMID:1268168", "title": "A clinical evaluation of the applanation pneumatonograph.", "content": "The applanation pneumatonograph combines pneumatic and electronic systems. It is used for measuring intraocular pressure, aqueous humour dynamics, and ocular pulsation. In the present study the PTG and the Goldmann tonometer have been used to measure the intraocular pressure in 40 normal and 40 glaucomatous eyes. It has been found that the results of the two instruments correlate well. The PTG readings have, generally, been found to be higher with a mean difference of 0-75 mmHg in the normal and 1-25 mmHg in the glaucomatous eye. The mean ocular pulse as determined in normal eyes was 3-25 +/-0-21 mmHg.", "contents": "A clinical evaluation of the applanation pneumatonograph. The applanation pneumatonograph combines pneumatic and electronic systems. It is used for measuring intraocular pressure, aqueous humour dynamics, and ocular pulsation. In the present study the PTG and the Goldmann tonometer have been used to measure the intraocular pressure in 40 normal and 40 glaucomatous eyes. It has been found that the results of the two instruments correlate well. The PTG readings have, generally, been found to be higher with a mean difference of 0-75 mmHg in the normal and 1-25 mmHg in the glaucomatous eye. The mean ocular pulse as determined in normal eyes was 3-25 +/-0-21 mmHg."} {"id": "PMID:1268170", "title": "Provocative tests in closed-angle glaucoma.", "content": "Altogether 119 eyes at risk of developing closed-angle glaucoma were provoked with simultaneous pilocarpine and phenylephrine; of these 74 developed closed-angle glaucoma. The remaining 45 eyes were re-provoked with tropicamide and a further nine developed closed-angle glaucoma. The 36 eyes in which all tests were negative were given no treatment and have been observed for a period of 1 to 7 years (mean 3 years). One has developed closed-angle glaucoma. A scheme for provoking eyes at risk of developing closed-angle glaucoma is described.", "contents": "Provocative tests in closed-angle glaucoma. Altogether 119 eyes at risk of developing closed-angle glaucoma were provoked with simultaneous pilocarpine and phenylephrine; of these 74 developed closed-angle glaucoma. The remaining 45 eyes were re-provoked with tropicamide and a further nine developed closed-angle glaucoma. The 36 eyes in which all tests were negative were given no treatment and have been observed for a period of 1 to 7 years (mean 3 years). One has developed closed-angle glaucoma. A scheme for provoking eyes at risk of developing closed-angle glaucoma is described."} {"id": "PMID:1268171", "title": "The syndrome of closed-angle glaucoma.", "content": "Closed-angle glaucoma is the result of two mechanisms acting either separately or in combination: 1. Pupil block creates a greater pressure in the posterior than in the anterior chamber, pushing the iris on to the cornea. 2. Increased trabecular meshwork outflow in the presence of pupil block creates a lower pressure in the anterior chamber than in the posterior, pulling the iris on to the cornea. Three main groups of eyes manifest closed-angle glaucoma: (i) Mechanism (I) is necessary and sufficient, but (2) precludes the development of angle closure. (ii) Mechanism (I) is necessary but insufficient. Mechanism (2) must also be present. (iii) Mechanism (I) is necessary and sufficient but (I) and (2) may combine to produce an acute attack.", "contents": "The syndrome of closed-angle glaucoma. Closed-angle glaucoma is the result of two mechanisms acting either separately or in combination: 1. Pupil block creates a greater pressure in the posterior than in the anterior chamber, pushing the iris on to the cornea. 2. Increased trabecular meshwork outflow in the presence of pupil block creates a lower pressure in the anterior chamber than in the posterior, pulling the iris on to the cornea. Three main groups of eyes manifest closed-angle glaucoma: (i) Mechanism (I) is necessary and sufficient, but (2) precludes the development of angle closure. (ii) Mechanism (I) is necessary but insufficient. Mechanism (2) must also be present. (iii) Mechanism (I) is necessary and sufficient but (I) and (2) may combine to produce an acute attack."} {"id": "PMID:1268172", "title": "Intraocular surgery in advanced glaucoma.", "content": "Loss of visual field subserving macular function has been found to be rare after intraocular surgery in advanced glaucoma. Abrupt changes in refractive error, lens opacity, and suppression must be carefully excluded before macular fixation is deemed lost. Out of 69 intraocular procedures (46 drainage operations, 13 cataract extractons) two patients lost central visual field subserving macular fixation possibly as a result of surgery. There is an increased incidence of postoperative maculopathy in late glaucoma. Three drainage operations out of 46 and four cataract extractions out of 13 had this complication. Altogether 30% of drainage procedures induced deterioration of visual acuity of lenticular origin to a level normally requiring cataract extraction. Trabeculectomy was found to be less likely to cause this sequela than the Scheie procedure at the 6 month postoperative stage. However, 77% of patients with advanced glaucoma and cataract obtained a satisfactory improvement in visual status after cataract extraction.", "contents": "Intraocular surgery in advanced glaucoma. Loss of visual field subserving macular function has been found to be rare after intraocular surgery in advanced glaucoma. Abrupt changes in refractive error, lens opacity, and suppression must be carefully excluded before macular fixation is deemed lost. Out of 69 intraocular procedures (46 drainage operations, 13 cataract extractons) two patients lost central visual field subserving macular fixation possibly as a result of surgery. There is an increased incidence of postoperative maculopathy in late glaucoma. Three drainage operations out of 46 and four cataract extractions out of 13 had this complication. Altogether 30% of drainage procedures induced deterioration of visual acuity of lenticular origin to a level normally requiring cataract extraction. Trabeculectomy was found to be less likely to cause this sequela than the Scheie procedure at the 6 month postoperative stage. However, 77% of patients with advanced glaucoma and cataract obtained a satisfactory improvement in visual status after cataract extraction."} {"id": "PMID:1268173", "title": "Clinical assessment of rhodopsin in the eye. Using a standard fundus camera and a photographic technique.", "content": "A technique based on the method of differential fundus reflectometry is used to assess the availability of rhodopsin in the eye. A defined part of the dark adapted fundus is bleached by a short intense flash of light. The fundus is subsequently photographed in order to record the flux reflected from the bleached area, the optogram, and the surrounding unbleached region. This procedure requires only a few simple modifications to a Zeiss fundus camera before it can be used routinely in the clinic.", "contents": "Clinical assessment of rhodopsin in the eye. Using a standard fundus camera and a photographic technique. A technique based on the method of differential fundus reflectometry is used to assess the availability of rhodopsin in the eye. A defined part of the dark adapted fundus is bleached by a short intense flash of light. The fundus is subsequently photographed in order to record the flux reflected from the bleached area, the optogram, and the surrounding unbleached region. This procedure requires only a few simple modifications to a Zeiss fundus camera before it can be used routinely in the clinic."} {"id": "PMID:1268174", "title": "Plasma amino-acids in hereditary retinal disease. Ornithine, lysine, and taurine.", "content": "Plasma free amino-acids were measured in 41 patients with hereditary chorio-retinal degenerations including 26 with retinitis pigmentosa and five with gyrate atrophy of the choroid, six relatives of patients with gyrate atrophy, and 13 normal subjects. Patients with gyrate atrophy had very increased levels of ornithine and slightly decreased mean lysine values. Most relatives had slightly increased ornithine. Taurine, known to be deficient in the plasma of casein-fed cats with photoreceptor degeneration, was normal in all patients. Amino-acid precursors and metabolites of ornithine and taurine were also normal in the plasma. Although the association of high ornithine and gyrate atrophy appears constant, high levels of ornithine alone do not necessarily lead to this degeneration; one patient with known hyperammonaemia, homocitrullinuria and a tenfold increase in plasma ornithine was found to have a normal fundus appearance and normal electroretinogram.", "contents": "Plasma amino-acids in hereditary retinal disease. Ornithine, lysine, and taurine. Plasma free amino-acids were measured in 41 patients with hereditary chorio-retinal degenerations including 26 with retinitis pigmentosa and five with gyrate atrophy of the choroid, six relatives of patients with gyrate atrophy, and 13 normal subjects. Patients with gyrate atrophy had very increased levels of ornithine and slightly decreased mean lysine values. Most relatives had slightly increased ornithine. Taurine, known to be deficient in the plasma of casein-fed cats with photoreceptor degeneration, was normal in all patients. Amino-acid precursors and metabolites of ornithine and taurine were also normal in the plasma. Although the association of high ornithine and gyrate atrophy appears constant, high levels of ornithine alone do not necessarily lead to this degeneration; one patient with known hyperammonaemia, homocitrullinuria and a tenfold increase in plasma ornithine was found to have a normal fundus appearance and normal electroretinogram."} {"id": "PMID:1268176", "title": "Retinoblastoma occurring in four successive generations.", "content": "Retinoblastoma occurring in four successive generations is described, followed by a brief discussion on the mode of inheritance of these tumours.", "contents": "Retinoblastoma occurring in four successive generations. Retinoblastoma occurring in four successive generations is described, followed by a brief discussion on the mode of inheritance of these tumours."} {"id": "PMID:1268178", "title": "Nocturnal lagophthalmos and recurrent erosion.", "content": "The symptoms and corneal changes caused by sleeping with one or both eyes open are described in 102 patients. The clinical picture is identical to that of the microform recurrent erosion. The close relationship between the micro- and macro-forms of recurrent corneal erosion suggests that the latter condition is also precipitated by nocturnal lagophthalmos.", "contents": "Nocturnal lagophthalmos and recurrent erosion. The symptoms and corneal changes caused by sleeping with one or both eyes open are described in 102 patients. The clinical picture is identical to that of the microform recurrent erosion. The close relationship between the micro- and macro-forms of recurrent corneal erosion suggests that the latter condition is also precipitated by nocturnal lagophthalmos."} {"id": "PMID:1268179", "title": "Scleritis and episcleritis.", "content": "The data from 159 patients (217 eyes) with episscleritis and 207 patients (301 eyes) with scleritis have been investigated in detail and the results analysed with the help of a computer. Of these patients, 91 per cent were followed-up during a period of one to eight years. A new classification is presented which is as follows: Episcleritis (217 eyes) Simple episcleritis (170 eyes) Nodular episcleritis (47 eyes) Scleritis (301 eyes) Diffuse anterior scleritis (119 eyes) Nodular anterior scleritis (134 eyes) Necrotizing scleritis (42 eyes). Of these, 13 were regarded as scleromalacia perforans. Posterior scleritis (6 eyes) The diagnosis is based on an exact clinical examination which is fully described. Episcleritis has been shown to be a benign recurring condition, a mild keratitis being the only occasional complication. Episcleritis does not progress to scleritis, except in the case of herpes zoster which sometimes starts as an episcleritis with the vesicular stage of the eruption, to reappear three months later as a scleritis in the same site. No clear conclusions could be drawn as to the aetiology of episcleritis.", "contents": "Scleritis and episcleritis. The data from 159 patients (217 eyes) with episscleritis and 207 patients (301 eyes) with scleritis have been investigated in detail and the results analysed with the help of a computer. Of these patients, 91 per cent were followed-up during a period of one to eight years. A new classification is presented which is as follows: Episcleritis (217 eyes) Simple episcleritis (170 eyes) Nodular episcleritis (47 eyes) Scleritis (301 eyes) Diffuse anterior scleritis (119 eyes) Nodular anterior scleritis (134 eyes) Necrotizing scleritis (42 eyes). Of these, 13 were regarded as scleromalacia perforans. Posterior scleritis (6 eyes) The diagnosis is based on an exact clinical examination which is fully described. Episcleritis has been shown to be a benign recurring condition, a mild keratitis being the only occasional complication. Episcleritis does not progress to scleritis, except in the case of herpes zoster which sometimes starts as an episcleritis with the vesicular stage of the eruption, to reappear three months later as a scleritis in the same site. No clear conclusions could be drawn as to the aetiology of episcleritis."} {"id": "PMID:1268181", "title": "Evaluation of eyes enucleated for scleritis.", "content": "A series of 30 enucleated eyes, all of which had a primary histological diagnosis of scleritis, was analysed. The average age of patients at enucleation was 68 years; many of these patients had had the disease for more than 30 years. In 40 per cent the diagnosis of scleritis was unsuspected and was often masked by multiple complications. Scleritis with uveitis and glaucoma was the most common combination to come to enucleation. In 82 per cent, pain was the reason for enucleation, which suggests that some patients were on inadequate levels of steroid treatment or were unable to tolerate them. In the series, 37 per cent of the eyes perforated. Perforation occurred in those patients who were having steriods but not in those who were not, but the data are inconclusive as to which method of steroid administration was most likely to cause ocular perforation.", "contents": "Evaluation of eyes enucleated for scleritis. A series of 30 enucleated eyes, all of which had a primary histological diagnosis of scleritis, was analysed. The average age of patients at enucleation was 68 years; many of these patients had had the disease for more than 30 years. In 40 per cent the diagnosis of scleritis was unsuspected and was often masked by multiple complications. Scleritis with uveitis and glaucoma was the most common combination to come to enucleation. In 82 per cent, pain was the reason for enucleation, which suggests that some patients were on inadequate levels of steroid treatment or were unable to tolerate them. In the series, 37 per cent of the eyes perforated. Perforation occurred in those patients who were having steriods but not in those who were not, but the data are inconclusive as to which method of steroid administration was most likely to cause ocular perforation."} {"id": "PMID:1268182", "title": "The effects of dietary histidine, methionine and homocystine on vitamin B12 and folate levels in rat liver.", "content": "1. L-histidine (20 g/kg) added to vitamin B12-deficient and cyanocobalamin-supplemented diets based on soya-bean flour reduced the growth of rats given the vitamin B12-deficient diet but stimulated growth of rats given the cyanocobalamin-supplemented diet. Liver weight (g/kg body-weight)increased, but the protein content of the livers decreased, in rats given histidine supplements. The histidine was associated with significantly higher folate concentrations in the livers of cyanocobalamin-supplemented rats.", "contents": "The effects of dietary histidine, methionine and homocystine on vitamin B12 and folate levels in rat liver. 1. L-histidine (20 g/kg) added to vitamin B12-deficient and cyanocobalamin-supplemented diets based on soya-bean flour reduced the growth of rats given the vitamin B12-deficient diet but stimulated growth of rats given the cyanocobalamin-supplemented diet. Liver weight (g/kg body-weight)increased, but the protein content of the livers decreased, in rats given histidine supplements. The histidine was associated with significantly higher folate concentrations in the livers of cyanocobalamin-supplemented rats."} {"id": "PMID:1268183", "title": "The utilization of diets containing acetate salts by growing lambs as measured by comparative slaughter and respiration calorimetry, together with rumen fermentation.", "content": "1. In a comparative slaughter experiment, growing lambs were given concentrate diets in which 14 or 19% metabolizable energy (ME) provided by barley was replaced by sodium, calcium and potassium salts of acetic acid. As the proportion of ME as acetate was increased, energy retention decreased. ME intake was 9271, 9430, and 9217 +/- 67 kJ/d and energy retention was 2698, 2422 and 2280 +/- 71 kJ/d for the diets containong 0, 14 or 19% ME as acetate respectively. There were no differences in protein deposition. The efficiency of utilization of acetate for energy retention (kf) was calculated by difference to be 3 and 10 +/- 13% respectively for the diets containing 14 and 19% ME as acetate.", "contents": "The utilization of diets containing acetate salts by growing lambs as measured by comparative slaughter and respiration calorimetry, together with rumen fermentation. 1. In a comparative slaughter experiment, growing lambs were given concentrate diets in which 14 or 19% metabolizable energy (ME) provided by barley was replaced by sodium, calcium and potassium salts of acetic acid. As the proportion of ME as acetate was increased, energy retention decreased. ME intake was 9271, 9430, and 9217 +/- 67 kJ/d and energy retention was 2698, 2422 and 2280 +/- 71 kJ/d for the diets containong 0, 14 or 19% ME as acetate respectively. There were no differences in protein deposition. The efficiency of utilization of acetate for energy retention (kf) was calculated by difference to be 3 and 10 +/- 13% respectively for the diets containing 14 and 19% ME as acetate."} {"id": "PMID:1268184", "title": "Mechanisms of heat damage in proteins. 7. The significance lysine-containing isopeptides and of lanthionine in heated proteins.", "content": "1. Studies have been made with solvent-extracted chicken muscle, bovine plasma albumin (BPA) and other proteins, all severely heated in the absence of carbohydrates so as to cause a large decrease in their fluorodinitrobenzene (FDNB)-reactive lysine contents. 2. epsilon-N-(beta-L-aspartyl)-L-lysine and epsilon-N-(gamma-L-glutamyl)-L-lysine isopeptides were determined after enzymic digestion of heated chicken muscle, and their content was found to increase as the material was subjected to more heat treatment. Heated chicken muscle was not found to contain lanthionine. Heated BPA, on the other hand, was found to contain lanthionine but not the isopeptides. Both lanthionine and isopeptide cross-linkages were detected in most of the other heated proteins. There was some difficulty in quantifying the amounts of isopeptides formed on heat treatment, because the enzymic digestion procedure used in their isolation appeared to be incomplete. Neither lysinoalanine nor ornithinoalanine was detected in any of the test materials.", "contents": "Mechanisms of heat damage in proteins. 7. The significance lysine-containing isopeptides and of lanthionine in heated proteins. 1. Studies have been made with solvent-extracted chicken muscle, bovine plasma albumin (BPA) and other proteins, all severely heated in the absence of carbohydrates so as to cause a large decrease in their fluorodinitrobenzene (FDNB)-reactive lysine contents. 2. epsilon-N-(beta-L-aspartyl)-L-lysine and epsilon-N-(gamma-L-glutamyl)-L-lysine isopeptides were determined after enzymic digestion of heated chicken muscle, and their content was found to increase as the material was subjected to more heat treatment. Heated chicken muscle was not found to contain lanthionine. Heated BPA, on the other hand, was found to contain lanthionine but not the isopeptides. Both lanthionine and isopeptide cross-linkages were detected in most of the other heated proteins. There was some difficulty in quantifying the amounts of isopeptides formed on heat treatment, because the enzymic digestion procedure used in their isolation appeared to be incomplete. Neither lysinoalanine nor ornithinoalanine was detected in any of the test materials."} {"id": "PMID:1268185", "title": "The effect of feeding on the motility of the stomach and small intestine in the pig.", "content": "1. Electromyographical studies were made on the motility of the stomach and small intestine of five pigs when given a standard diet either ad lib. or as one or two meals/d. Recordings were made from electrodes placed chronically on the antrum, the duodenum and the jejuno-ileum, and a continuous 24 h recording was made every 2d for a period of 4 weeks. A simple \"T\"-shaped cannula was positioned in the proximal duodenum in two of the pigs.", "contents": "The effect of feeding on the motility of the stomach and small intestine in the pig. 1. Electromyographical studies were made on the motility of the stomach and small intestine of five pigs when given a standard diet either ad lib. or as one or two meals/d. Recordings were made from electrodes placed chronically on the antrum, the duodenum and the jejuno-ileum, and a continuous 24 h recording was made every 2d for a period of 4 weeks. A simple \"T\"-shaped cannula was positioned in the proximal duodenum in two of the pigs."} {"id": "PMID:1268186", "title": "Light-induced glutamate transport in Halobacterium halobium envelope vesicles. I. Kinetics of the light-dependent and the sodium-gradient-dependent uptake.", "content": "During illumination Halobacterium halobium cell envelope vesicles accumulate [3H]glutamate by an apparently unidirectional transport system. The driving force for the active transport originates from the light-dependent translocation of protons by bacteriorhodopsin and is due to a transmembrane electrical potential rather than a pH difference. Transport of glutamate against high concentration gradients is also achieved in the dark, with high outside/inside Na+ gradients. Transport in both cases proceeds with similar kinetics and shows a requirement for Na+ on the outside and for K+ on the inside of the vesicles. The unidirectional nature of glutamate transport seems to be due to the low permeability of the membranes to the anionic glutamate, and to the differential cation requirement of the carrier on the two sides of the membrane for substrate translocation. Thus, glutamate gradients can be collapsed in the dark either by lowering the intravesicle pH (with nigericin, or carbonyl cyanide p-trifluoromethoxyphenylhydrazone plus valinomycin), or by reversing the cation balance across the membranes, i.e., providing NaCl on the inside and KCl on the outside of the vesicles. In contrast to the case of light-dependent glutamate transport, the initial rates of Na+-gradient-dependent transport are not depressed when an opposing diffusion potential is introduced by adding the membrane-permeant cation, triphenylmethylphosphonium bromide. Therefore, it appears that, although the electrical potential must be the primary source of energy for the light-dependent transport, the translocation step itself is electrically neutral.", "contents": "Light-induced glutamate transport in Halobacterium halobium envelope vesicles. I. Kinetics of the light-dependent and the sodium-gradient-dependent uptake. During illumination Halobacterium halobium cell envelope vesicles accumulate [3H]glutamate by an apparently unidirectional transport system. The driving force for the active transport originates from the light-dependent translocation of protons by bacteriorhodopsin and is due to a transmembrane electrical potential rather than a pH difference. Transport of glutamate against high concentration gradients is also achieved in the dark, with high outside/inside Na+ gradients. Transport in both cases proceeds with similar kinetics and shows a requirement for Na+ on the outside and for K+ on the inside of the vesicles. The unidirectional nature of glutamate transport seems to be due to the low permeability of the membranes to the anionic glutamate, and to the differential cation requirement of the carrier on the two sides of the membrane for substrate translocation. Thus, glutamate gradients can be collapsed in the dark either by lowering the intravesicle pH (with nigericin, or carbonyl cyanide p-trifluoromethoxyphenylhydrazone plus valinomycin), or by reversing the cation balance across the membranes, i.e., providing NaCl on the inside and KCl on the outside of the vesicles. In contrast to the case of light-dependent glutamate transport, the initial rates of Na+-gradient-dependent transport are not depressed when an opposing diffusion potential is introduced by adding the membrane-permeant cation, triphenylmethylphosphonium bromide. Therefore, it appears that, although the electrical potential must be the primary source of energy for the light-dependent transport, the translocation step itself is electrically neutral."} {"id": "PMID:1268187", "title": "Molecular flow resonance Raman effect from retinal and rhodopsin.", "content": "We have performed resonance enhanced Raman measurements of retinal isomers in solution (all-trans, 11-cis, 9-cis, and 13-cis) and cetyltrimethylammonium bromide (CTAB) detergent extracts of bovine rhodopsin near physiological temperatures (17 degrees C). In order to measure these photolabile systems, we have developed a general technique which allows Raman measurements of any photosensitive material. This technique involves imposing a molecular velocity transverse to the Raman exciting laser beam sufficient to ensure that any given molecule moves through the beam so that it has little probability of absorbing a photon. We have also measured the resonance Raman spectra of crystals of the same retinal isomers. The data show that each isomer has a distinct and characteristic Raman spectra and that the spectrum of 11-cis-retinal is quite similar but not identical with that of rhodopsin and similarly for 9-cis-retinal compared with isorhodopsin. In agreement with previous work, the Raman data demonstrate that retinal and opsin are joined by a protonated Schiff base. Due to the fact that the Raman spectra of 11-cis-retinal (solution) and rhodopsin show bands near 998 and 1018 cm(-1), a spectral region previously assigned to C-Me stretching motions, it is suggested that 11-cis-retinal in solution is compased of a mixture of 12-s-trans and 12-s-cis, and that the conformation of rhodopsin is (perhaps distorted) 12-s-trans.", "contents": "Molecular flow resonance Raman effect from retinal and rhodopsin. We have performed resonance enhanced Raman measurements of retinal isomers in solution (all-trans, 11-cis, 9-cis, and 13-cis) and cetyltrimethylammonium bromide (CTAB) detergent extracts of bovine rhodopsin near physiological temperatures (17 degrees C). In order to measure these photolabile systems, we have developed a general technique which allows Raman measurements of any photosensitive material. This technique involves imposing a molecular velocity transverse to the Raman exciting laser beam sufficient to ensure that any given molecule moves through the beam so that it has little probability of absorbing a photon. We have also measured the resonance Raman spectra of crystals of the same retinal isomers. The data show that each isomer has a distinct and characteristic Raman spectra and that the spectrum of 11-cis-retinal is quite similar but not identical with that of rhodopsin and similarly for 9-cis-retinal compared with isorhodopsin. In agreement with previous work, the Raman data demonstrate that retinal and opsin are joined by a protonated Schiff base. Due to the fact that the Raman spectra of 11-cis-retinal (solution) and rhodopsin show bands near 998 and 1018 cm(-1), a spectral region previously assigned to C-Me stretching motions, it is suggested that 11-cis-retinal in solution is compased of a mixture of 12-s-trans and 12-s-cis, and that the conformation of rhodopsin is (perhaps distorted) 12-s-trans."} {"id": "PMID:1268188", "title": "Primary structure and microheterogeneities of rat chloroleukemia histone H2A (histone ALK, IIbl or F2a2).", "content": "Rat chloroleukemia histone H2A, obtained from the F2a2 fraction, has been eluted in two peaks from a Biorex 70 column. The amino acid sequence of rat chloroleukemia histone H2A has been determined and compared to that of calf-thymus histone H2A. The structural studies performed on the tryptic peptides from the maleylated histone and on the thermolysin peptides from the native histone clearly demonstrate the existence of three molecular species of histone H2A depending on the nature of the amino acid residue at positions 16 and 99: H2A-alpha (Ser-16 and Lys-99) accounts for 60% and H2A-betaI (Thr-16 and Arg-99) and H2A-betaII (Ser-16 and Arg-99) for 20% each. A threonine residue at position 16 and a lysine residue at position 99 have been found in calf-thymus histone H2A.", "contents": "Primary structure and microheterogeneities of rat chloroleukemia histone H2A (histone ALK, IIbl or F2a2). Rat chloroleukemia histone H2A, obtained from the F2a2 fraction, has been eluted in two peaks from a Biorex 70 column. The amino acid sequence of rat chloroleukemia histone H2A has been determined and compared to that of calf-thymus histone H2A. The structural studies performed on the tryptic peptides from the maleylated histone and on the thermolysin peptides from the native histone clearly demonstrate the existence of three molecular species of histone H2A depending on the nature of the amino acid residue at positions 16 and 99: H2A-alpha (Ser-16 and Lys-99) accounts for 60% and H2A-betaI (Thr-16 and Arg-99) and H2A-betaII (Ser-16 and Arg-99) for 20% each. A threonine residue at position 16 and a lysine residue at position 99 have been found in calf-thymus histone H2A."} {"id": "PMID:1268189", "title": "Interactions of mercury and copper with constitutive heterochromatin and euchromatin in vivo and in vitro.", "content": "Mouse liver nuclei were fractionated into (condensed) heterochromatin and (noncondensed) euchromatin by differential centrifugation of sonicated nuclei. The fractions were subsequently characterized as unique nuclear species by thermal denaturation derivative profile analysis, which revealed the heterochromatin fraction enriched in satellite DNA and by endogenous metal content, which displayed partitioning of mercury in euchromatin over heterochromatin by a 10:1 ratio, with a comparatively uniform distribution of copper in both fractions. Fractionation of nuclei following in vivo challenge with copper showed enrichment of copper in heterochromatin, relative to euchromatin, while in vivo exposure to mercury resulted in a 20-fold accumulation of mercury in euchromatin, relative to heterochromatin. Using gel filtration and equilibrium dialysis to measure in vitro binding under relatively physiologic conditions of pH (6.0-7.0) and ionic strength (standard saline citrate or saline), the condensed and noncondensed chromatin fractions exhibited binding specificities toward mercury and copper similar to that observed in the in vivo metal challenge experiments. The level of mercury which binds to euchromatin in vitro, when measured either in physiologic [standard saline citrate (SSC)] or in dilute (1:100 SSC) salt solutions, was comparable (approximately 3 mug of Hg/mg of DNA) to that of in vivo euchromatin-bound mercury after 1 month of challenge with dietary metal. In contrast, copper showed little or no preference for the nuclear fractions in dilute salt solutions and displayed patterns which mimic in vivo binding only at higher ionic strengths (saline). Removal of proteins from the chromatin fractions resulted in a loss of binding specificity toward both metals. Therefore, the binding selectivity of condensed and noncondensed chromatin toward both mercury and copper appears to arise from protein or from protein-DNA associations. The state of chromatin condensation is especially critical in the case of copper.", "contents": "Interactions of mercury and copper with constitutive heterochromatin and euchromatin in vivo and in vitro. Mouse liver nuclei were fractionated into (condensed) heterochromatin and (noncondensed) euchromatin by differential centrifugation of sonicated nuclei. The fractions were subsequently characterized as unique nuclear species by thermal denaturation derivative profile analysis, which revealed the heterochromatin fraction enriched in satellite DNA and by endogenous metal content, which displayed partitioning of mercury in euchromatin over heterochromatin by a 10:1 ratio, with a comparatively uniform distribution of copper in both fractions. Fractionation of nuclei following in vivo challenge with copper showed enrichment of copper in heterochromatin, relative to euchromatin, while in vivo exposure to mercury resulted in a 20-fold accumulation of mercury in euchromatin, relative to heterochromatin. Using gel filtration and equilibrium dialysis to measure in vitro binding under relatively physiologic conditions of pH (6.0-7.0) and ionic strength (standard saline citrate or saline), the condensed and noncondensed chromatin fractions exhibited binding specificities toward mercury and copper similar to that observed in the in vivo metal challenge experiments. The level of mercury which binds to euchromatin in vitro, when measured either in physiologic [standard saline citrate (SSC)] or in dilute (1:100 SSC) salt solutions, was comparable (approximately 3 mug of Hg/mg of DNA) to that of in vivo euchromatin-bound mercury after 1 month of challenge with dietary metal. In contrast, copper showed little or no preference for the nuclear fractions in dilute salt solutions and displayed patterns which mimic in vivo binding only at higher ionic strengths (saline). Removal of proteins from the chromatin fractions resulted in a loss of binding specificity toward both metals. Therefore, the binding selectivity of condensed and noncondensed chromatin toward both mercury and copper appears to arise from protein or from protein-DNA associations. The state of chromatin condensation is especially critical in the case of copper."} {"id": "PMID:1268190", "title": "Interactions between model proteins and deoxyribonucleic acids.", "content": "Interactions between DNA and model proteins, poly(L-Lys(m)L-Ala(n)), where m + n = 100%, have been investigated using thermal denaturation and circular dichroism (CD). All complexes of DNA with these proteins precipitate in a small range of input ratios, protein to DNA, with the midpoints of all precipitation curves close to a 1:1 ratio of lysine to phosphate. The melting temperature of model protein-bound DNA regions decreases slightly as the alanine content of the model protein is increased, which can be explained as a result of insufficient charge neutralization of phosphates by lysine residues in the model proteins. In the free state, these model proteins possess varying amounts of alpha helix, random coil, or a mixture of these two, depending upon the relative lysine/alanine content. When bound to DNA, the CD of the complex shows a substantial increase in alpha-helical structure for those model proteins with 40-60% alanine, while there is no significant change in alpha-helical structure when the percent alanine is either substantially higher or lower (i.e., 81 or 19% alanine). Only those complexes formed with model proteins having 40-60% alanine undergo a drastic transition from a B-type CD to an A-type in the presence of intermediate ionic strength (0.2 M NaCl, for example). Poly(Lys19Ala81)-DNA complexes show a slight transition toward A-type CD at 0.4 M NaCl or higher. Apparently other factors, in addition to alanine and alpha-helical content, must be responsible for this B leads to A transition. At the other extreme of lysine/alanine ratio, with high lysine content, poly(Lys81Ala19) or polylysine, the presence of NaCl produces a B leads to psi transition. The possible significance of these differences in response to the binding of these model proteins is discussed.", "contents": "Interactions between model proteins and deoxyribonucleic acids. Interactions between DNA and model proteins, poly(L-Lys(m)L-Ala(n)), where m + n = 100%, have been investigated using thermal denaturation and circular dichroism (CD). All complexes of DNA with these proteins precipitate in a small range of input ratios, protein to DNA, with the midpoints of all precipitation curves close to a 1:1 ratio of lysine to phosphate. The melting temperature of model protein-bound DNA regions decreases slightly as the alanine content of the model protein is increased, which can be explained as a result of insufficient charge neutralization of phosphates by lysine residues in the model proteins. In the free state, these model proteins possess varying amounts of alpha helix, random coil, or a mixture of these two, depending upon the relative lysine/alanine content. When bound to DNA, the CD of the complex shows a substantial increase in alpha-helical structure for those model proteins with 40-60% alanine, while there is no significant change in alpha-helical structure when the percent alanine is either substantially higher or lower (i.e., 81 or 19% alanine). Only those complexes formed with model proteins having 40-60% alanine undergo a drastic transition from a B-type CD to an A-type in the presence of intermediate ionic strength (0.2 M NaCl, for example). Poly(Lys19Ala81)-DNA complexes show a slight transition toward A-type CD at 0.4 M NaCl or higher. Apparently other factors, in addition to alanine and alpha-helical content, must be responsible for this B leads to A transition. At the other extreme of lysine/alanine ratio, with high lysine content, poly(Lys81Ala19) or polylysine, the presence of NaCl produces a B leads to psi transition. The possible significance of these differences in response to the binding of these model proteins is discussed."} {"id": "PMID:1268191", "title": "Characterization of the oligosaccharide units of the bovine erythrocyte membrane glycoprotein.", "content": "The major glycoprotein of the bovine erythrocyte membrane was purified by extraction of the ghosts with lithium 3,5-diiodosalicylate followed by phenol-water extraction and acidification. The glycoprotein contains 20% protein and 80% carbohydrate by weight and gives a single band on sodium dodecyl sulfate-polyacrylamide gels with an estimated molecular weight of 230000 daltons. The carbohydrate composition of the glycoprotein was determined to be (in residues relative to sialic acid): sialic acid, 1.0; fucose, less than 0.01; mannose, 0.1; galactose, 3.3; N-acetylgalactosamine, 0.9; and N-acetylglucosamine, 2.4. Pronase digestion of the isolated glycoprotein followed by Sephadex G-75 gel filtration resulted in the separation of a small pool of glycopeptides (pool III), which included all of the mannose-containing glycopeptides, from the bulk of the glycopeptide material which was in the void fractions of the column (pool I). Alkaline borohydride treatment released over 95% of the oligosaccharide units in pool I and approximately 30% of the oligosaccharide units in pool III. These oligosaccharides were isolated by gel filtration and ion-exchange chromatography. The oligosaccharides released from pool I had molecular weights of 1100-1400 daltons and contained sialic acid, galactose, and N-acetylglucosamine in molar ratios of 0.5-1:3:2 as well as a partial residue of N-acetylgalactosaminitol. The oligosaccharides released from pool III by alkali had molecular weights of 1300-1600 daltons and contained sialic acid, galactose, N-acetylglucosamine, N-acetylgalactosamine and N-ACETYLgalactosaminitol in molar ratios of 1-2:2:1:1:1. These data indicate that the majority of the oligosaccharide units of the bovine erythrocyte glycoprotein are linked O-glycosidically to the peptide backbone of the molecule.", "contents": "Characterization of the oligosaccharide units of the bovine erythrocyte membrane glycoprotein. The major glycoprotein of the bovine erythrocyte membrane was purified by extraction of the ghosts with lithium 3,5-diiodosalicylate followed by phenol-water extraction and acidification. The glycoprotein contains 20% protein and 80% carbohydrate by weight and gives a single band on sodium dodecyl sulfate-polyacrylamide gels with an estimated molecular weight of 230000 daltons. The carbohydrate composition of the glycoprotein was determined to be (in residues relative to sialic acid): sialic acid, 1.0; fucose, less than 0.01; mannose, 0.1; galactose, 3.3; N-acetylgalactosamine, 0.9; and N-acetylglucosamine, 2.4. Pronase digestion of the isolated glycoprotein followed by Sephadex G-75 gel filtration resulted in the separation of a small pool of glycopeptides (pool III), which included all of the mannose-containing glycopeptides, from the bulk of the glycopeptide material which was in the void fractions of the column (pool I). Alkaline borohydride treatment released over 95% of the oligosaccharide units in pool I and approximately 30% of the oligosaccharide units in pool III. These oligosaccharides were isolated by gel filtration and ion-exchange chromatography. The oligosaccharides released from pool I had molecular weights of 1100-1400 daltons and contained sialic acid, galactose, and N-acetylglucosamine in molar ratios of 0.5-1:3:2 as well as a partial residue of N-acetylgalactosaminitol. The oligosaccharides released from pool III by alkali had molecular weights of 1300-1600 daltons and contained sialic acid, galactose, N-acetylglucosamine, N-acetylgalactosamine and N-ACETYLgalactosaminitol in molar ratios of 1-2:2:1:1:1. These data indicate that the majority of the oligosaccharide units of the bovine erythrocyte glycoprotein are linked O-glycosidically to the peptide backbone of the molecule."} {"id": "PMID:1268192", "title": "A procedure for the quantitative recovery of homogeneous populations of undegraded free and bound polysomes from rat liver.", "content": "A procedure is described for the preparation of free and bound polysomes from whole homogenates of rat liver tissue. Liver is homogenized in a conventional medium containing glutathione; then after a 12-min centrifugation at 131000g, the free polysomes in the supernatant are saved, while the membrane-bound polysomes in the pellet are suspended in a mixture of ribonuclease inhibitors (cell sap, 250 mM KCl, and glutathione), homogenized in the presence of detergent (Triton X-100), centirfuged for 5 min at 1470g, decanted, and treated with deoxycholate; the polysomes in the two supernatants are harvested by centrifugation through sucrose gradients containing 250 mM KCl and cell sap. Free and bound polysomes prepared in this manner are undegraded, equally active in cell-free protein synthesis, and virtually free of ribonuclease, membranous material, glycogen, deoxycholate, completed protein, and cross-contamination. The recovery of polysomes is approximately 95% and the distribution between the free and membrane-bound state is 25 and 75%, respectively. The molecular weight profiles after sodium dodecyl sulfate-acrylamide gel electrophoresis of the polypeptides completed and released by free and bound polysomes in vitro are different, indicating that there are quantitative differences in the synthesis of various size polypeptides between the two polysome classes. The differential centrifugation procedure is rapid and reproducible, requires much less ultracentrifugation than the isopycnic technique, and provides a nearly quantitative means of separating free and bound polysomes.", "contents": "A procedure for the quantitative recovery of homogeneous populations of undegraded free and bound polysomes from rat liver. A procedure is described for the preparation of free and bound polysomes from whole homogenates of rat liver tissue. Liver is homogenized in a conventional medium containing glutathione; then after a 12-min centrifugation at 131000g, the free polysomes in the supernatant are saved, while the membrane-bound polysomes in the pellet are suspended in a mixture of ribonuclease inhibitors (cell sap, 250 mM KCl, and glutathione), homogenized in the presence of detergent (Triton X-100), centirfuged for 5 min at 1470g, decanted, and treated with deoxycholate; the polysomes in the two supernatants are harvested by centrifugation through sucrose gradients containing 250 mM KCl and cell sap. Free and bound polysomes prepared in this manner are undegraded, equally active in cell-free protein synthesis, and virtually free of ribonuclease, membranous material, glycogen, deoxycholate, completed protein, and cross-contamination. The recovery of polysomes is approximately 95% and the distribution between the free and membrane-bound state is 25 and 75%, respectively. The molecular weight profiles after sodium dodecyl sulfate-acrylamide gel electrophoresis of the polypeptides completed and released by free and bound polysomes in vitro are different, indicating that there are quantitative differences in the synthesis of various size polypeptides between the two polysome classes. The differential centrifugation procedure is rapid and reproducible, requires much less ultracentrifugation than the isopycnic technique, and provides a nearly quantitative means of separating free and bound polysomes."} {"id": "PMID:1268193", "title": "Kinetics of recombination of the subunits of human chorionic gonadotropin. Effect of subunit concentration.", "content": "The rate of formation of human chorionic gonadotropin from its alpha and beta subunits has been measured at neutral pH and 37 degrees C as a function of subunit concentration, using the fluorescence probe, 1,8-anilinoaphthalene-sulfonate (ANS), to monitor the reaction. The subunits were prepared by acid dissociation of the intact hormone (pH less than or equal to 2, 37 degrees C). Following neutralization, the rate of appearance of ANS fluorescence was identical with the rate of recovery of receptor binding activity and both of these properties were completely recovered. Kinetic data obtained over a 100-fold range of subunit concentrations (1.5 to 146 muM) were not compatible with a simple second-order reaction scheme, but required at least one additional step. The data were best fit by a model in which the subunits reversibly form an intermediate complex (alpha + beta in equilibrium alphabeta) which then undergoes a conformational rearrangement to form the native structure (alphabeta leads to H). Ultraviolet difference absorption measurements suggest that most of the change in the environment of the tyrosyl residues occurs during this second step.", "contents": "Kinetics of recombination of the subunits of human chorionic gonadotropin. Effect of subunit concentration. The rate of formation of human chorionic gonadotropin from its alpha and beta subunits has been measured at neutral pH and 37 degrees C as a function of subunit concentration, using the fluorescence probe, 1,8-anilinoaphthalene-sulfonate (ANS), to monitor the reaction. The subunits were prepared by acid dissociation of the intact hormone (pH less than or equal to 2, 37 degrees C). Following neutralization, the rate of appearance of ANS fluorescence was identical with the rate of recovery of receptor binding activity and both of these properties were completely recovered. Kinetic data obtained over a 100-fold range of subunit concentrations (1.5 to 146 muM) were not compatible with a simple second-order reaction scheme, but required at least one additional step. The data were best fit by a model in which the subunits reversibly form an intermediate complex (alpha + beta in equilibrium alphabeta) which then undergoes a conformational rearrangement to form the native structure (alphabeta leads to H). Ultraviolet difference absorption measurements suggest that most of the change in the environment of the tyrosyl residues occurs during this second step."} {"id": "PMID:1268194", "title": "The chemical modification of papain with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide.", "content": "The reaction of the water-soluble carbodimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), with active papain in the presence of the nucleophile ethyl glycinate results in an irreversible inactivation of the enzyme. This inactivation is accompanied by the derivatization of the catalytically essential thiol group of the enzyme (Cys-25) and by the modification of 6 out of 14 of papain's carboxyl groups and up to 9 out of 19 of the enyzme's tyrosyl residues. No apparent irreversible modification of histidine residues is observed. Mercuripapain is also irreversibly inactivated by EDC/ethyl glycinate, again with the concomitant modification of 6 carboxyl groups, up to 10 tyrosyl residues, and no histidine residues; but in this case there is no thiol derivatization. Treatment of either modified native papain or modified mercuripapain with hydroxylamine results in the complete regeneration of free tyrosyl residues but does not restore any activity. The competitive inhibitor benzamidoacetonitrile substantially protects native papain against inactivation and against the derivatization of the essential thiol group as well as 2 of the 6 otherwise accessible carboxyl groups. The inhibitor has no effect upon tyrosyl modification. These findings are discussed in the context of a possible catalytic role for a carboxyl group in the active site of papain.", "contents": "The chemical modification of papain with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The reaction of the water-soluble carbodimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), with active papain in the presence of the nucleophile ethyl glycinate results in an irreversible inactivation of the enzyme. This inactivation is accompanied by the derivatization of the catalytically essential thiol group of the enzyme (Cys-25) and by the modification of 6 out of 14 of papain's carboxyl groups and up to 9 out of 19 of the enyzme's tyrosyl residues. No apparent irreversible modification of histidine residues is observed. Mercuripapain is also irreversibly inactivated by EDC/ethyl glycinate, again with the concomitant modification of 6 carboxyl groups, up to 10 tyrosyl residues, and no histidine residues; but in this case there is no thiol derivatization. Treatment of either modified native papain or modified mercuripapain with hydroxylamine results in the complete regeneration of free tyrosyl residues but does not restore any activity. The competitive inhibitor benzamidoacetonitrile substantially protects native papain against inactivation and against the derivatization of the essential thiol group as well as 2 of the 6 otherwise accessible carboxyl groups. The inhibitor has no effect upon tyrosyl modification. These findings are discussed in the context of a possible catalytic role for a carboxyl group in the active site of papain."} {"id": "PMID:1268195", "title": "Kinetic studies on the inactivation of L-lactate oxidase by [the acetylenic suicide substrate] 2-hydroxy-3-butynoate.", "content": "2-Hydroxy-3-butynoate is both a substrate and an irreversible inactivator of the flavoenzyme L-lactate oxidase. The partitioning between catalytic oxidation of 2-hydroxy-3-butynoate and inactivation of the enzyme is determined by the concentration of the second substrate, O2. Rapid reaction studies show the formation of an intermediate which is common to both the oxidation and inactivation pathways. This intermediate appears to be a charge-transfer complex between enzyme-reduced flavin and 2-keto-3-butynoate. It is characterized by a long-wavelength absorbing band (gamma(max) 600 nm) and lack of fluorescence, making it easily distinguished from the subsequently formed inactivated enzyme, which has no long wavelength absorption (gamma(max) 318, 368 nm) and which is strongly fluorescent. Inactivation is also accomplished by reaction of the reduced enzyme with 2-keto-3-butynoate. The absorbance and fluorescence characteristics of the inactivated enzyme are similar to those of a model compound, C(4a), N(5)-propano-bridged FMN bound to apolactate oxidase. That the modified chromophore of the inactivated enzyme is an adduct involving both the C(4a) and N5 positions is further supported by the spectral and fluorescence changes resulting from treatment of the inactivated enzyme with borohydride.", "contents": "Kinetic studies on the inactivation of L-lactate oxidase by [the acetylenic suicide substrate] 2-hydroxy-3-butynoate. 2-Hydroxy-3-butynoate is both a substrate and an irreversible inactivator of the flavoenzyme L-lactate oxidase. The partitioning between catalytic oxidation of 2-hydroxy-3-butynoate and inactivation of the enzyme is determined by the concentration of the second substrate, O2. Rapid reaction studies show the formation of an intermediate which is common to both the oxidation and inactivation pathways. This intermediate appears to be a charge-transfer complex between enzyme-reduced flavin and 2-keto-3-butynoate. It is characterized by a long-wavelength absorbing band (gamma(max) 600 nm) and lack of fluorescence, making it easily distinguished from the subsequently formed inactivated enzyme, which has no long wavelength absorption (gamma(max) 318, 368 nm) and which is strongly fluorescent. Inactivation is also accomplished by reaction of the reduced enzyme with 2-keto-3-butynoate. The absorbance and fluorescence characteristics of the inactivated enzyme are similar to those of a model compound, C(4a), N(5)-propano-bridged FMN bound to apolactate oxidase. That the modified chromophore of the inactivated enzyme is an adduct involving both the C(4a) and N5 positions is further supported by the spectral and fluorescence changes resulting from treatment of the inactivated enzyme with borohydride."} {"id": "PMID:1268196", "title": "The structure of the covalent flavin adduct formed between lactate oxidase and the suicide substrate 2-hydroxy-3-butynoate.", "content": "2-Hydroxy-3-butynoic acid is a suicide substrate for Mycobacterium smegmatis lactate oxidase. Inactivation occurs by covalent modification of enzyme-bound FMN and does not involve labeling of the apoprotein. The spectrum of the enzyme bound adduct suggests that it is a 4a, 5-dihydroflavin derivative. When this adduct is released from the enzyme, a complex mixture of unstable compounds is obtained. When the initially formed enzyme-bound adduct is reduced with NaBH4, a major stable species can be resolved from the enzyme and can be isolated and purified. The structure was established by appropriate isotope substitutions. Fourier transform NMR spectroscopy, chemical reactivity, and synthesis of a model compound. The structure of the isolated adduct is structure II, Scheme II. The structure proposed for the adduct initially formed on the enzyme is structure VII, Scheme II.", "contents": "The structure of the covalent flavin adduct formed between lactate oxidase and the suicide substrate 2-hydroxy-3-butynoate. 2-Hydroxy-3-butynoic acid is a suicide substrate for Mycobacterium smegmatis lactate oxidase. Inactivation occurs by covalent modification of enzyme-bound FMN and does not involve labeling of the apoprotein. The spectrum of the enzyme bound adduct suggests that it is a 4a, 5-dihydroflavin derivative. When this adduct is released from the enzyme, a complex mixture of unstable compounds is obtained. When the initially formed enzyme-bound adduct is reduced with NaBH4, a major stable species can be resolved from the enzyme and can be isolated and purified. The structure was established by appropriate isotope substitutions. Fourier transform NMR spectroscopy, chemical reactivity, and synthesis of a model compound. The structure of the isolated adduct is structure II, Scheme II. The structure proposed for the adduct initially formed on the enzyme is structure VII, Scheme II."} {"id": "PMID:1268197", "title": "The activation of factor V by factor Xa or alpha-chymotrypsin and comparison with thrombin and RVV-V action. An improved factor V isolation procedure.", "content": "Bovine plasma factor V has been isolated by a preparative procedure involving barium sulfate adsorption, QAEC extraction, poly(ethylene glycol) precipitation, and finally chromatography on a desulfated Sepharose 6B column. Factor V was recovered as a single peak in yields of 35-40% with a specific activity of 50-70 representing a purification of 1000-2000-fold relative to the starting plasma. The apparent molecular weight of the purified factor V was 439,000 +/- 5000. On sodium dodecyl sulfate gel and analytical gel electrophoresis, this factor V preparation showed multiple bands, but results are inconclusive with regard to a possible subunit structure for this factor. The purified factor V was stable for at least 1-2 weeks when stored at 4 degrees C in 0.2 M Tris-acetate, 50 mM CaCl2, 10% glycerol, pH 7.5. When stored at -20 degrees C in 50% glycerol, this preparation was stable for several months. Treatment of the purified factor V with bovine factor Xa, RVV-V, thrombin, or chymotrypsin (but not trypsin) led to a seven- to ten-fold increase in clotting activity and a concomitant decrease in apparent molecular weight. The latter was comparable for each activation system yielding the following average molecular weight values: factor VaSa, 246,000-, factor Va RVV-V, 251,500; Factor Vathr, 239,000; alpha-chymotrypsin, but not trypsin, can activate plasma factor V yielding a product similar to that observed with the above activators. The molar quantities of each of the activators required varied considerably with thrombin having the highest specific activity and factor Xa the lowest. Activation by factor Xa was greatly facilitated by the addition of phospholipid. In the presence of a mixture of phosphatidylcholine/phosphatidylserine (1:1, w/w), the activation of factor V by factor Xa plus Ca2+ required one-third the amount of factor Xa protein as that required in the absence of phospholipid. Even though each of these activators appears to act in an enzymatic manner, the chemical nature of the conversion is unknown at this time.", "contents": "The activation of factor V by factor Xa or alpha-chymotrypsin and comparison with thrombin and RVV-V action. An improved factor V isolation procedure. Bovine plasma factor V has been isolated by a preparative procedure involving barium sulfate adsorption, QAEC extraction, poly(ethylene glycol) precipitation, and finally chromatography on a desulfated Sepharose 6B column. Factor V was recovered as a single peak in yields of 35-40% with a specific activity of 50-70 representing a purification of 1000-2000-fold relative to the starting plasma. The apparent molecular weight of the purified factor V was 439,000 +/- 5000. On sodium dodecyl sulfate gel and analytical gel electrophoresis, this factor V preparation showed multiple bands, but results are inconclusive with regard to a possible subunit structure for this factor. The purified factor V was stable for at least 1-2 weeks when stored at 4 degrees C in 0.2 M Tris-acetate, 50 mM CaCl2, 10% glycerol, pH 7.5. When stored at -20 degrees C in 50% glycerol, this preparation was stable for several months. Treatment of the purified factor V with bovine factor Xa, RVV-V, thrombin, or chymotrypsin (but not trypsin) led to a seven- to ten-fold increase in clotting activity and a concomitant decrease in apparent molecular weight. The latter was comparable for each activation system yielding the following average molecular weight values: factor VaSa, 246,000-, factor Va RVV-V, 251,500; Factor Vathr, 239,000; alpha-chymotrypsin, but not trypsin, can activate plasma factor V yielding a product similar to that observed with the above activators. The molar quantities of each of the activators required varied considerably with thrombin having the highest specific activity and factor Xa the lowest. Activation by factor Xa was greatly facilitated by the addition of phospholipid. In the presence of a mixture of phosphatidylcholine/phosphatidylserine (1:1, w/w), the activation of factor V by factor Xa plus Ca2+ required one-third the amount of factor Xa protein as that required in the absence of phospholipid. Even though each of these activators appears to act in an enzymatic manner, the chemical nature of the conversion is unknown at this time."} {"id": "PMID:1268198", "title": "Quantitation of labeled globin messenger RNA by hybridization with excess complementary DNA covalently bound to cellulose.", "content": "A method is described to quantitate labeled globin mRNA by hybridization with excess cDNA which was enzymatically polymerized on oligo(dT)-cellulose. In a large excess of cDNA-cellulose the rate of RNA hybridization was dependent on DNA concentration and not on RNA concentration. Nonhybridized RNA can be digested by RNase and washed from the cDNA which is covalently bound to cellulose. This enables the detection of labeled globin mRNA even when present in a porportion as low as 0.02-0.03% of the total RNA.", "contents": "Quantitation of labeled globin messenger RNA by hybridization with excess complementary DNA covalently bound to cellulose. A method is described to quantitate labeled globin mRNA by hybridization with excess cDNA which was enzymatically polymerized on oligo(dT)-cellulose. In a large excess of cDNA-cellulose the rate of RNA hybridization was dependent on DNA concentration and not on RNA concentration. Nonhybridized RNA can be digested by RNase and washed from the cDNA which is covalently bound to cellulose. This enables the detection of labeled globin mRNA even when present in a porportion as low as 0.02-0.03% of the total RNA."} {"id": "PMID:1268199", "title": "Erythrocyte spectrin. Purification in deoxycholate and preliminary characterization.", "content": "Erythrocyte spectrin, isolated by aqueous extraction of erythrocyte ghosts, may be freed from contaminating membrane lipids and small amounts of other proteins by gel chromatography in 5 or 10 mM deoxycholate. The purified protein, in deoxycholate, is a mixture of monomers and dimers, both highly asymmetric molecules. The hydrodynamic properties of the dimer closely resemble those of muscle myosin, and spectrin and myosin also have similar circular dichroism spectra. The proportion of dimer to monomer in the purified protein varies from one preparation to another, an observation for which there is no simple explanation. In the absence of deoxycholate, spectrin associated beyond the dimer stage, possibly by loose end-to-end aggregation involving hydrophobic forces.", "contents": "Erythrocyte spectrin. Purification in deoxycholate and preliminary characterization. Erythrocyte spectrin, isolated by aqueous extraction of erythrocyte ghosts, may be freed from contaminating membrane lipids and small amounts of other proteins by gel chromatography in 5 or 10 mM deoxycholate. The purified protein, in deoxycholate, is a mixture of monomers and dimers, both highly asymmetric molecules. The hydrodynamic properties of the dimer closely resemble those of muscle myosin, and spectrin and myosin also have similar circular dichroism spectra. The proportion of dimer to monomer in the purified protein varies from one preparation to another, an observation for which there is no simple explanation. In the absence of deoxycholate, spectrin associated beyond the dimer stage, possibly by loose end-to-end aggregation involving hydrophobic forces."} {"id": "PMID:1268200", "title": "Hydrolysis of tri- and monoacylglycerol by lipoprotein lipase: evidence for a common active site.", "content": "The relationship between triacylglycerol and monoacylglycerol hydrolyzing activities of purified rat heart lipoprotein lipase was studied using emulsified trioleoylglycerol and micellar or albumin-bound monooleoylglycerol as substrates. The maximal reaction rates obtained with the two substrates were similar (650 and 550 nmol of fatty acid released per min per mg of protein, respectively). Addition of apolipoprotein C-II or serum increased the maximal reaction rate for the trioleolyglycerol hydrolyzing activity about four-fold, but had no effect on the monooleolyglycerol hydrolyzing activity. Hydolysis of the two substrates apparently takes place at the same active site of the enzyme since (1) mutual competitive inhibition between the substrates could be demonstrated; (2) the rate of inactivation of enzymatic activity with the two substrates in 1.2 M NaCl was the same; (3) similar losses of hydrolytic activity with tri- and monooleoylglycerol were observed in the presence of low concentrations of n-butyl (p-nitrophenyl) carbamide; (4) inhibition of both hydrolytic activities by this compound could be prevented by prior exposure of lipoprotein lipase to either substrate.", "contents": "Hydrolysis of tri- and monoacylglycerol by lipoprotein lipase: evidence for a common active site. The relationship between triacylglycerol and monoacylglycerol hydrolyzing activities of purified rat heart lipoprotein lipase was studied using emulsified trioleoylglycerol and micellar or albumin-bound monooleoylglycerol as substrates. The maximal reaction rates obtained with the two substrates were similar (650 and 550 nmol of fatty acid released per min per mg of protein, respectively). Addition of apolipoprotein C-II or serum increased the maximal reaction rate for the trioleolyglycerol hydrolyzing activity about four-fold, but had no effect on the monooleolyglycerol hydrolyzing activity. Hydolysis of the two substrates apparently takes place at the same active site of the enzyme since (1) mutual competitive inhibition between the substrates could be demonstrated; (2) the rate of inactivation of enzymatic activity with the two substrates in 1.2 M NaCl was the same; (3) similar losses of hydrolytic activity with tri- and monooleoylglycerol were observed in the presence of low concentrations of n-butyl (p-nitrophenyl) carbamide; (4) inhibition of both hydrolytic activities by this compound could be prevented by prior exposure of lipoprotein lipase to either substrate."} {"id": "PMID:1268201", "title": "Effect of bridging the two essential thiols of myosin on its spectral and actin-binding properties.", "content": "The circular dichroic and fluorescent spectral properties of the myosin head (subfragment I (SFI)) modified by covalently bridging the two essential thiol groups have been examined. CD spectra of SFI with the two thiols linked through reaction with a bifunctional reagent, N, N'- p-phenylenedimaleimide, show enhancement of the 282-nm minimum similar to that observed for the long-lived kinetic intermediate (Mg**MgADP-Pi) formed during the ATP cleavage reaction. No significant perturbation of the CD band at 282 nm is seen on blocking both thiol groups with the monofunctional reagent N-ethylmaleimide. The fluorescence emission maximum also shifts to lower wavelengths following covalent bridging (from 343 to 340 nm), but no change in fluorescent intensity has been detected. Formation of the covalent bridge completely inhibits interaction of the modified protein with F-actin. These results suggest that the local conformational state of the polypeptide chain formed on bridging the two thiol groups exhibits certain similarities with the state produced following binding of MgATP to native myosin.", "contents": "Effect of bridging the two essential thiols of myosin on its spectral and actin-binding properties. The circular dichroic and fluorescent spectral properties of the myosin head (subfragment I (SFI)) modified by covalently bridging the two essential thiol groups have been examined. CD spectra of SFI with the two thiols linked through reaction with a bifunctional reagent, N, N'- p-phenylenedimaleimide, show enhancement of the 282-nm minimum similar to that observed for the long-lived kinetic intermediate (Mg**MgADP-Pi) formed during the ATP cleavage reaction. No significant perturbation of the CD band at 282 nm is seen on blocking both thiol groups with the monofunctional reagent N-ethylmaleimide. The fluorescence emission maximum also shifts to lower wavelengths following covalent bridging (from 343 to 340 nm), but no change in fluorescent intensity has been detected. Formation of the covalent bridge completely inhibits interaction of the modified protein with F-actin. These results suggest that the local conformational state of the polypeptide chain formed on bridging the two thiol groups exhibits certain similarities with the state produced following binding of MgATP to native myosin."} {"id": "PMID:1268202", "title": "Protein kinases of the chick oviduct: a study of the cytoplasmic and nuclear enzymes.", "content": "Subcellular fractionation of oviduct tissue from estrogen-treated chicks indicated that the bulk of the protein kinase activity of this tissue is located in the cytoplasmic and nuclear fractions, DEAE-cellulose chromatography of cytosol revealed a major peak of cAMP stimulatable activity eluting at 0.2 M KCl. This peak was further characterized and found to exhibit properties consistent with cytoplasmic cAMP dependent protein kinases isolated from other tissues; it had a Km for ATP of 2 X 10(-5) M, preferred basic proteins such as histones, as substrate, and had a M of 165 000. Addition of 10(-6) M cAMP caused the holoenzyme to dissociate into cAMP binding regulatory subunit and a protein kinase catalytic subunit. Extraction of purified oviduct nuclei with 0.3 M KCl released greater than 80% of the kinase activity in this fraction. Upon elution from phospho-cellulose, the nuclear extract was resolved into two equal peaks of kinase activity (designated I and II). Peak I had a sedimentation coefficient of 3S and a Km for ATP of 13 muM. while peak II had a sedimentation coefficient of 6S and a Km for ATP of 9 muM. Both enzymes preferred alpha-casein as a substrate over phosvitin or whole histone, although they exhibited different salt-activity profiles. The cytoplasmic and nuclear enzymes were well separated on phospho-cellulose and this resin was used to quantitate the amount of cAMP dependent histone kinase activity in the nucleus and the amount of casein kinase activity in the cytosol. Protein kinase activity in nuclei from estrogen-stimulated chicks was found to be 40% greater than hormone-withdrawn animals. This increase in activity was not due to translocation of the cytoplasmic protein kinase in response to hormone, but to an increase in nuclear (casein) kinase activity. During the course of this work, we observed small but significant amounts of cAMP binding activity very tightly bound to the nuclear fraction. Solubilization of the binding activity by sonication in high salt allowed comparison studies to be performed which indicated that the nuclear binding protein is identical with the cytoplasmic cAMP binding regulatory subunit. The possible role of the nuclear binding activity is discussed.", "contents": "Protein kinases of the chick oviduct: a study of the cytoplasmic and nuclear enzymes. Subcellular fractionation of oviduct tissue from estrogen-treated chicks indicated that the bulk of the protein kinase activity of this tissue is located in the cytoplasmic and nuclear fractions, DEAE-cellulose chromatography of cytosol revealed a major peak of cAMP stimulatable activity eluting at 0.2 M KCl. This peak was further characterized and found to exhibit properties consistent with cytoplasmic cAMP dependent protein kinases isolated from other tissues; it had a Km for ATP of 2 X 10(-5) M, preferred basic proteins such as histones, as substrate, and had a M of 165 000. Addition of 10(-6) M cAMP caused the holoenzyme to dissociate into cAMP binding regulatory subunit and a protein kinase catalytic subunit. Extraction of purified oviduct nuclei with 0.3 M KCl released greater than 80% of the kinase activity in this fraction. Upon elution from phospho-cellulose, the nuclear extract was resolved into two equal peaks of kinase activity (designated I and II). Peak I had a sedimentation coefficient of 3S and a Km for ATP of 13 muM. while peak II had a sedimentation coefficient of 6S and a Km for ATP of 9 muM. Both enzymes preferred alpha-casein as a substrate over phosvitin or whole histone, although they exhibited different salt-activity profiles. The cytoplasmic and nuclear enzymes were well separated on phospho-cellulose and this resin was used to quantitate the amount of cAMP dependent histone kinase activity in the nucleus and the amount of casein kinase activity in the cytosol. Protein kinase activity in nuclei from estrogen-stimulated chicks was found to be 40% greater than hormone-withdrawn animals. This increase in activity was not due to translocation of the cytoplasmic protein kinase in response to hormone, but to an increase in nuclear (casein) kinase activity. During the course of this work, we observed small but significant amounts of cAMP binding activity very tightly bound to the nuclear fraction. Solubilization of the binding activity by sonication in high salt allowed comparison studies to be performed which indicated that the nuclear binding protein is identical with the cytoplasmic cAMP binding regulatory subunit. The possible role of the nuclear binding activity is discussed."} {"id": "PMID:1268203", "title": "Histone-histone interactions within chromatin. Crosslinking studies using ultraviolet light.", "content": "Irradiation of either whole cells or chromatin at 280 nm results in the covalent linkage of histones 2A and 2B, presumably at their mutual binding sites. The reaction is specific and proceeds with high yield (about 80%). Irradiation of reconstituted nucleohistone containing only H2A, H2B and DNA also yields the H2A-H2B dimer. The cross-linking event is sensitive to the conformation of the H2A-H2B pair since the histones must be bound to DNA for maximum cross-linking specificity at low ionic strength. However, the histones must first interact with each other before being deposited on the DNA, since separate addition of the histones to the DNA yields no dimer upon irradiation. If irradiation is conducted at 254 nm rather than 280 nm, DNA-histone cross-linking appears to dominate.", "contents": "Histone-histone interactions within chromatin. Crosslinking studies using ultraviolet light. Irradiation of either whole cells or chromatin at 280 nm results in the covalent linkage of histones 2A and 2B, presumably at their mutual binding sites. The reaction is specific and proceeds with high yield (about 80%). Irradiation of reconstituted nucleohistone containing only H2A, H2B and DNA also yields the H2A-H2B dimer. The cross-linking event is sensitive to the conformation of the H2A-H2B pair since the histones must be bound to DNA for maximum cross-linking specificity at low ionic strength. However, the histones must first interact with each other before being deposited on the DNA, since separate addition of the histones to the DNA yields no dimer upon irradiation. If irradiation is conducted at 254 nm rather than 280 nm, DNA-histone cross-linking appears to dominate."} {"id": "PMID:1268204", "title": "Transferrin uptake and release by reticulocytes treated with proteolytic enzymes and neuraminidase.", "content": "The mechanism of transferrin uptake by reticulocytes was investigated using rabbit transferrin labelled with 125I and 59Fe and rabbit reticulocytes which had been treated with trypsin, Pronase or neuraminidase. Low concentrations of the proteolytic enzymes produced a small increase in transferrin and iron uptake by the cells. However, higher concentrations or incubation of the cells with the enzymes for longer periods caused a marked fall in transferrin and iron uptake. This fall was associated with a reduction in the proportion of cellular transferrin which was bound to a cell membrane component solubilized with the non-ionic detergent, Teric 12A9. The effect of trypsin and Pronase on transferrin release from the cells was investigated in the absence and in the presence of N-ethylmaleimide which inhibits the normal process of transferrin release. It was found that only a small proportion of transferrin which had been taken up by reticulocytes at 37 degrees C but nearly all that taken up 4 degrees C was released when the cells were subsequently incubated with trypsin plus N-ethylmaleimide, despite the fact that about 80% of the 59Fe in the cells was released in both instances. Neuraminidase produced no change in transferrin and iron uptake by the cells. These experiments provide evidence that transferrin uptake by reticulocytes requires interaction with a receptor which is protein in nature and that following uptake at 37 degrees C, most of the transferrin is located at a site unavailable to the action of proteolytic enzymes. The results support the hypothesis that transferrin enters reticulocytes by endocytosis.", "contents": "Transferrin uptake and release by reticulocytes treated with proteolytic enzymes and neuraminidase. The mechanism of transferrin uptake by reticulocytes was investigated using rabbit transferrin labelled with 125I and 59Fe and rabbit reticulocytes which had been treated with trypsin, Pronase or neuraminidase. Low concentrations of the proteolytic enzymes produced a small increase in transferrin and iron uptake by the cells. However, higher concentrations or incubation of the cells with the enzymes for longer periods caused a marked fall in transferrin and iron uptake. This fall was associated with a reduction in the proportion of cellular transferrin which was bound to a cell membrane component solubilized with the non-ionic detergent, Teric 12A9. The effect of trypsin and Pronase on transferrin release from the cells was investigated in the absence and in the presence of N-ethylmaleimide which inhibits the normal process of transferrin release. It was found that only a small proportion of transferrin which had been taken up by reticulocytes at 37 degrees C but nearly all that taken up 4 degrees C was released when the cells were subsequently incubated with trypsin plus N-ethylmaleimide, despite the fact that about 80% of the 59Fe in the cells was released in both instances. Neuraminidase produced no change in transferrin and iron uptake by the cells. These experiments provide evidence that transferrin uptake by reticulocytes requires interaction with a receptor which is protein in nature and that following uptake at 37 degrees C, most of the transferrin is located at a site unavailable to the action of proteolytic enzymes. The results support the hypothesis that transferrin enters reticulocytes by endocytosis."} {"id": "PMID:1268205", "title": "Effect of phase transition on the distribution of membrane-associated particles in microsomes.", "content": "(1) Rat liver microsomes were studied by freeze-fracture electron microscopy. The distribution of membrane-associated particles indicated the right-side-out orientation of microsomal vesicles. Studies at different temperatures were performed. At 30 degrees C membrane-associated particles are randomly distributed on membrane A-faces, while aggregations of particles are observed at 4 degrees C. (2) Aggregation is dependent on the cooling rates. It can be prevented by shock-freezing. (3) Particle aggregation is also prevented by cholesterol, added to the microsomes in equal molar ratio to the microsomal phospholid content. (4) These findings suggest that particle aggregation is caused by a partial freezing-out of phospholipid molecules during the phase transition from the liquid-crystalline to the gel state. (5) The results are discussed with respect to an observed increase in activation energy of microsomal drug monooxygenation at lower temperature.", "contents": "Effect of phase transition on the distribution of membrane-associated particles in microsomes. (1) Rat liver microsomes were studied by freeze-fracture electron microscopy. The distribution of membrane-associated particles indicated the right-side-out orientation of microsomal vesicles. Studies at different temperatures were performed. At 30 degrees C membrane-associated particles are randomly distributed on membrane A-faces, while aggregations of particles are observed at 4 degrees C. (2) Aggregation is dependent on the cooling rates. It can be prevented by shock-freezing. (3) Particle aggregation is also prevented by cholesterol, added to the microsomes in equal molar ratio to the microsomal phospholid content. (4) These findings suggest that particle aggregation is caused by a partial freezing-out of phospholipid molecules during the phase transition from the liquid-crystalline to the gel state. (5) The results are discussed with respect to an observed increase in activation energy of microsomal drug monooxygenation at lower temperature."} {"id": "PMID:1268206", "title": "Factors affecting the motion of the polar headgroup in phospholipid bilayers. A 31P NMR study of unsonicated phosphatidylcholine liposomes.", "content": "(1) The 129 MHZ and 36.4 MHZ 31 P NMR spectra of unsonicated liposomes consisting of phosphatidylcholines of varying chain length and unsaturation have been investigated. (2) In the liquid crystalline state the 31 P NMR liposome spectra are similar for both saturated and unsaturated phosphatidylcholines, demonstrating that the motion of the polar headgroup is not sensitive to the fatty acid composition in the disordered liquid crystalline state. (3) Below the hydrocarbon phase transition temperature there is a marked increase in the linewidth of the 31P NMR liposome spectra, indicating a reduction in the motion of the polar headgroup. (4) The addition of equimolar concentrations of cholesterol to phosphatidylcholine eliminates phase transition effects experienced by the polar headgroup. The motion of the polar headgroup is then very similar to that obtained in the liquid crystalline state for pure phosphatidylcholine bilayers. (5) In the liquid crystalline state the motion of the polar headgroup in the phosphate region is insensitive to changes in the available area per phosphatidy-choline molecule.", "contents": "Factors affecting the motion of the polar headgroup in phospholipid bilayers. A 31P NMR study of unsonicated phosphatidylcholine liposomes. (1) The 129 MHZ and 36.4 MHZ 31 P NMR spectra of unsonicated liposomes consisting of phosphatidylcholines of varying chain length and unsaturation have been investigated. (2) In the liquid crystalline state the 31 P NMR liposome spectra are similar for both saturated and unsaturated phosphatidylcholines, demonstrating that the motion of the polar headgroup is not sensitive to the fatty acid composition in the disordered liquid crystalline state. (3) Below the hydrocarbon phase transition temperature there is a marked increase in the linewidth of the 31P NMR liposome spectra, indicating a reduction in the motion of the polar headgroup. (4) The addition of equimolar concentrations of cholesterol to phosphatidylcholine eliminates phase transition effects experienced by the polar headgroup. The motion of the polar headgroup is then very similar to that obtained in the liquid crystalline state for pure phosphatidylcholine bilayers. (5) In the liquid crystalline state the motion of the polar headgroup in the phosphate region is insensitive to changes in the available area per phosphatidy-choline molecule."} {"id": "PMID:1268207", "title": "Isolation of membrane glycoproteins by affinity chromatography in the presence of detergents.", "content": "Wheat germ agglutinin has been used in a one-step preparative method to isolate the major sialoglycoprotein (glycophorin A) from the human erythrocyte membrane. The conditions for isolation and purification of the sialoglycopeptide included low concentration of sodium dodecyl sulfate in the presence of relatively high salt concentration. This medium caused complete solubilization of the membrane but still allowed almost quantitative binding of the sialoglycopeptide to wheat germ agglutinin-Sepharose. The eluted protein from such affinity systems was found to be chemically comparable to glycophorin A, as prepared by other procedures.", "contents": "Isolation of membrane glycoproteins by affinity chromatography in the presence of detergents. Wheat germ agglutinin has been used in a one-step preparative method to isolate the major sialoglycoprotein (glycophorin A) from the human erythrocyte membrane. The conditions for isolation and purification of the sialoglycopeptide included low concentration of sodium dodecyl sulfate in the presence of relatively high salt concentration. This medium caused complete solubilization of the membrane but still allowed almost quantitative binding of the sialoglycopeptide to wheat germ agglutinin-Sepharose. The eluted protein from such affinity systems was found to be chemically comparable to glycophorin A, as prepared by other procedures."} {"id": "PMID:1268208", "title": "Effect of ethyl acetate on the transport of sodium and glucose in the hamster small intestine in vitro.", "content": "The effect of ethyl acetate on Na+, water and glucose transport, as well as on glucose and electrolyte intracellular concentrations in everted and cannulated sacs of hamster jejunum, have been studied. Ethyl acetate, a substance that easily penetrates and delivers energy to the cell, strongly stimulates net glucose and Na+ transport. The explanation of the experimental results takes into account the possibility of the existence of an active extrusion of glucose at the level of the basolateral membrane of the enterocyte.", "contents": "Effect of ethyl acetate on the transport of sodium and glucose in the hamster small intestine in vitro. The effect of ethyl acetate on Na+, water and glucose transport, as well as on glucose and electrolyte intracellular concentrations in everted and cannulated sacs of hamster jejunum, have been studied. Ethyl acetate, a substance that easily penetrates and delivers energy to the cell, strongly stimulates net glucose and Na+ transport. The explanation of the experimental results takes into account the possibility of the existence of an active extrusion of glucose at the level of the basolateral membrane of the enterocyte."} {"id": "PMID:1268209", "title": "Regulatory characteristics of amino acid transport in newborn rat renal cortex cells.", "content": "The uptaken of alpha-aminoisobutyric acid by slices of kidney cortex from newborn rats is enhanced by a preliminary incubation of the tissue in buffer at 37 degrees C. This effect is abolished by anaerobiosis, the presence of dinitrophenol or the removal of Na+ during the preliminary incubation. Cycloheximide (50 muM) and purimycin (1 mM) as well as alpha-aminoisobutyric acid, glycine and proline (5 mM) in the preincubation buffer also abolish the effect, while actinomycin D (0.8 muM) partially the phenomenon indicates that the enhanced uptake is due to an increased entry rate into the cells without a change in effux. There is no alteration in the apparent transport Km but an increase in the V for entry. The effect is dependent on tissue age being observed between birth and 22 days, after which there is a decrease in response to preliminary incubation with no effect seen in adult tissues.", "contents": "Regulatory characteristics of amino acid transport in newborn rat renal cortex cells. The uptaken of alpha-aminoisobutyric acid by slices of kidney cortex from newborn rats is enhanced by a preliminary incubation of the tissue in buffer at 37 degrees C. This effect is abolished by anaerobiosis, the presence of dinitrophenol or the removal of Na+ during the preliminary incubation. Cycloheximide (50 muM) and purimycin (1 mM) as well as alpha-aminoisobutyric acid, glycine and proline (5 mM) in the preincubation buffer also abolish the effect, while actinomycin D (0.8 muM) partially the phenomenon indicates that the enhanced uptake is due to an increased entry rate into the cells without a change in effux. There is no alteration in the apparent transport Km but an increase in the V for entry. The effect is dependent on tissue age being observed between birth and 22 days, after which there is a decrease in response to preliminary incubation with no effect seen in adult tissues."} {"id": "PMID:1268210", "title": "Tryptophan fluorescence and homology in lysozymes and alpha-lactalbumins.", "content": "Steady-state and transient fluorescence properties of turkey lysozyme, human lysozyme, and bovine alpha-lactalbumin are compared to those of hen lysozyme and hen lysozyme derivatives. Tryptophan fluorescence appears to be sufficiently sensitive to environment so that a small divergence in sequence can alter the fluorescence properties of one or more of the sequentially equivalent tryptophans in these proteins. Thus, an understanding of the fluorescence of one protein cannot necessarily be extended to a homologous protein in a simple manner, and the use of fluorescence to document structural similarity in homologous proteins is likely to be difficult. In addition, the results with alpha-lactalbumin and human lysozyme suggest that multiple conformations of these proteins exist in solution, and that interconversion of these conformations is slow compared to the fluorescence lifetime.", "contents": "Tryptophan fluorescence and homology in lysozymes and alpha-lactalbumins. Steady-state and transient fluorescence properties of turkey lysozyme, human lysozyme, and bovine alpha-lactalbumin are compared to those of hen lysozyme and hen lysozyme derivatives. Tryptophan fluorescence appears to be sufficiently sensitive to environment so that a small divergence in sequence can alter the fluorescence properties of one or more of the sequentially equivalent tryptophans in these proteins. Thus, an understanding of the fluorescence of one protein cannot necessarily be extended to a homologous protein in a simple manner, and the use of fluorescence to document structural similarity in homologous proteins is likely to be difficult. In addition, the results with alpha-lactalbumin and human lysozyme suggest that multiple conformations of these proteins exist in solution, and that interconversion of these conformations is slow compared to the fluorescence lifetime."} {"id": "PMID:1268211", "title": "Thermodynamics of the isothermal denaturation of lysozyme by guanidinium chloride.", "content": "A thermodynamic analysis of the isothermal denaturation of lysozyme by guanidinium chloride has been performed. The analysis is based on the equation which relates the equilibrium constant for denaturation to the preferential binding of denaturant. The equation has been derived previously by thermodynamic methods, whereas in this article a derivation based on statistical mechanics is given. By application of the equation the free energy of denaturation is first calculated and from it, by subtracting the calorimetrically-determined enthalpy of denaturation, the entropy of denaturation is determined.", "contents": "Thermodynamics of the isothermal denaturation of lysozyme by guanidinium chloride. A thermodynamic analysis of the isothermal denaturation of lysozyme by guanidinium chloride has been performed. The analysis is based on the equation which relates the equilibrium constant for denaturation to the preferential binding of denaturant. The equation has been derived previously by thermodynamic methods, whereas in this article a derivation based on statistical mechanics is given. By application of the equation the free energy of denaturation is first calculated and from it, by subtracting the calorimetrically-determined enthalpy of denaturation, the entropy of denaturation is determined."} {"id": "PMID:1268212", "title": "Preparation of the proteolipid apoprotein from bovine heart, liver and kidney.", "content": "Proteolipid apoproteins have been prepared from heart, kidney, and liver by dialysis in chloroform/methanol against chloroform/methanol, acidified chloroform/methanol, and chloroform/methanol in succession. They are free of lipids (less than 0.05% P; less than 0.1% carbohydrate). They show a high content of non-polar amino acids, methionine, and tryptophan and contain little or no half-cystine. The differ from neural proteolipid apoproteins by absence of half-cystine, and of covalently bound fatty acids. As recovered from chloroform/methanol solutions, they are soluble in chloroform/methanol and insoluble in water, but a water-soluble form can be prepared by changing the solvent from chloroform/methanol to water in a stream of nitrogen. The chloroform-methanol-soluble form and the water-soluble form are interconvertible. ORD and CD spectra of all proteolipid apoproteins indicate 60-70% alpha-helix content in chloroform/methanol solution and 20-30% alpha-helix in water solution. Sodium dodecyl sulfate gel electrophoresis resolves proteolipid apoprotein into two major components corresponding to ca. 12 000 and 34 000 daltons. With sodium dodecyl sulfate/urea numerous bands appear, with a major one at 30 000 daltons and 8 to 10, ranging downward to 2500. For comparison, neural proteolipid apoproteins also show numerous bands with a major one at 25 000. The marked chemical and physical similarities among all proteolipid apoproteins studied suggest a common role in membrane structures.", "contents": "Preparation of the proteolipid apoprotein from bovine heart, liver and kidney. Proteolipid apoproteins have been prepared from heart, kidney, and liver by dialysis in chloroform/methanol against chloroform/methanol, acidified chloroform/methanol, and chloroform/methanol in succession. They are free of lipids (less than 0.05% P; less than 0.1% carbohydrate). They show a high content of non-polar amino acids, methionine, and tryptophan and contain little or no half-cystine. The differ from neural proteolipid apoproteins by absence of half-cystine, and of covalently bound fatty acids. As recovered from chloroform/methanol solutions, they are soluble in chloroform/methanol and insoluble in water, but a water-soluble form can be prepared by changing the solvent from chloroform/methanol to water in a stream of nitrogen. The chloroform-methanol-soluble form and the water-soluble form are interconvertible. ORD and CD spectra of all proteolipid apoproteins indicate 60-70% alpha-helix content in chloroform/methanol solution and 20-30% alpha-helix in water solution. Sodium dodecyl sulfate gel electrophoresis resolves proteolipid apoprotein into two major components corresponding to ca. 12 000 and 34 000 daltons. With sodium dodecyl sulfate/urea numerous bands appear, with a major one at 30 000 daltons and 8 to 10, ranging downward to 2500. For comparison, neural proteolipid apoproteins also show numerous bands with a major one at 25 000. The marked chemical and physical similarities among all proteolipid apoproteins studied suggest a common role in membrane structures."} {"id": "PMID:1268213", "title": "The isolation and characterization of the glycopeptides from horseradish peroxidase isoenzyme C.", "content": "The purity of horseradish peroxidase isoenzyme C was demonstrated using isoelectric focusing, polyacrylamide gel electrophoresis at two pH values and cellulose acetate electrophoresis at two pH values. The glycopeptides obtained upon trypsin digestion were isolated using the plant lectin, concanavalin A, and were resolved using paper electrophoresis. The carbohydrate content of the native peroxidase was 86% accounted for by the carbohydrate content of the glycopeptides thus suggesting little loss of carbohydrate during glycopeptide isolation and purification. In each of the seven glycopeptides isolated glucosamine was associated with asparagine, thus suggesting the carbohydrate chains are covalently bound to the peptide chain through N-glycosidic linkages. The purity of each glycopeptide was demonstrated by the sequential release of single amino acid residues by Edman degradation. As six glycopeptides had unique amino acid sequences, it was concluded that the carbohydrate prosthetic group was distributed in at least six units along the protein backbone. Five glycopeptides possessed the amino acid sequence about the point of carbohydrate attachment of Asn-X-(Ser, Thr) where X is any amino acid. The size of the carbohydrate units ranged from 1600 to 3000 daltons. The predominant carbohydrate residues in each glycopeptide were mannose and glucosamine with lesser and varying amounts of fucose, xylose, and arabinose. There was no apparent correlation of the carbohydrate composition with the amino acid sequence.", "contents": "The isolation and characterization of the glycopeptides from horseradish peroxidase isoenzyme C. The purity of horseradish peroxidase isoenzyme C was demonstrated using isoelectric focusing, polyacrylamide gel electrophoresis at two pH values and cellulose acetate electrophoresis at two pH values. The glycopeptides obtained upon trypsin digestion were isolated using the plant lectin, concanavalin A, and were resolved using paper electrophoresis. The carbohydrate content of the native peroxidase was 86% accounted for by the carbohydrate content of the glycopeptides thus suggesting little loss of carbohydrate during glycopeptide isolation and purification. In each of the seven glycopeptides isolated glucosamine was associated with asparagine, thus suggesting the carbohydrate chains are covalently bound to the peptide chain through N-glycosidic linkages. The purity of each glycopeptide was demonstrated by the sequential release of single amino acid residues by Edman degradation. As six glycopeptides had unique amino acid sequences, it was concluded that the carbohydrate prosthetic group was distributed in at least six units along the protein backbone. Five glycopeptides possessed the amino acid sequence about the point of carbohydrate attachment of Asn-X-(Ser, Thr) where X is any amino acid. The size of the carbohydrate units ranged from 1600 to 3000 daltons. The predominant carbohydrate residues in each glycopeptide were mannose and glucosamine with lesser and varying amounts of fucose, xylose, and arabinose. There was no apparent correlation of the carbohydrate composition with the amino acid sequence."} {"id": "PMID:1268215", "title": "The demonstration of asymmetric hemoglobin hybrids by polyacrylamide electrophoresis.", "content": "A simpler, more economical technique than previously reported, that of conventional polyacrylamide gel electrophoresis alone, is described for the detection of asymmetric hemoglobin hybrids of the forms alphaXalphaYbeta2 and alpha2betaXbetaY when bloods from individuals with alpha and beta chain variants were examined. The presence of alpha chain variant hybrids, never before reported, is further evidence that hybrid formation is a more widespread phenomenon than has previously been thought of. Hybrids were found in artificial mixtures of hemoglobins and more importantly, are also reported here for the first time in bloods of individuals heterozygous for hemoglobin variants. These hybrid tetramers were as stable as the parent hemoglobins when examined under anaerobic conditions. The involvement of HbF in the formation of hybrids of the type alpha2betagamma is reported, and an analysis of the possible role of these as well as alpha2betaAbetaS hybrids in the sickling process is presented.", "contents": "The demonstration of asymmetric hemoglobin hybrids by polyacrylamide electrophoresis. A simpler, more economical technique than previously reported, that of conventional polyacrylamide gel electrophoresis alone, is described for the detection of asymmetric hemoglobin hybrids of the forms alphaXalphaYbeta2 and alpha2betaXbetaY when bloods from individuals with alpha and beta chain variants were examined. The presence of alpha chain variant hybrids, never before reported, is further evidence that hybrid formation is a more widespread phenomenon than has previously been thought of. Hybrids were found in artificial mixtures of hemoglobins and more importantly, are also reported here for the first time in bloods of individuals heterozygous for hemoglobin variants. These hybrid tetramers were as stable as the parent hemoglobins when examined under anaerobic conditions. The involvement of HbF in the formation of hybrids of the type alpha2betagamma is reported, and an analysis of the possible role of these as well as alpha2betaAbetaS hybrids in the sickling process is presented."} {"id": "PMID:1268217", "title": "Iron-binding activity of female-specific serum proteins of rainbow trout (Salmo gairdneri) and chum salmon (Oncorhyncus keta).", "content": "The differences of serum proteins between mature male and female rainbow trout (Salmo gairdneri) and chum salmon (Oncorhyncus keta) were studied electrophoretically and immunologically. Female-specific serum proteins were seen only in females of both species, in the same region as beta-globulin on cellulose acetate membrane electrophoresis and agarose gel immunoelectrophoresis. One of the female-specific serum proteins bound radioactive iron. This protein was partially purified by precipitation by lowering the ionic strength of the serum. The purified material also showed the iron-binding property.", "contents": "Iron-binding activity of female-specific serum proteins of rainbow trout (Salmo gairdneri) and chum salmon (Oncorhyncus keta). The differences of serum proteins between mature male and female rainbow trout (Salmo gairdneri) and chum salmon (Oncorhyncus keta) were studied electrophoretically and immunologically. Female-specific serum proteins were seen only in females of both species, in the same region as beta-globulin on cellulose acetate membrane electrophoresis and agarose gel immunoelectrophoresis. One of the female-specific serum proteins bound radioactive iron. This protein was partially purified by precipitation by lowering the ionic strength of the serum. The purified material also showed the iron-binding property."} {"id": "PMID:1268218", "title": "Disulfide-linked cyanogen bromide peptides of bovine fibrinogen. I. Isolation of peptide F-CB3 and characterization of its single disulfide bond by cleavage with cyanide.", "content": "A fragment F-CB3 which originates from the alpha-chain constituent of bovine fibrinogen could be liberated by CNBr cleavage and was purified by molecular sieve and ion-exchange chromatography. This fragment had a molecular weight of 36 000 and consisted of a single polypeptide chain which is folded into a loop by a single disulfide bridge. Further cleavage of F-CB3 by cyanide or by 2-nitro-5-thiocyanobenzoic acid gave rise to three fragments, CN1, CN2 and CN3, with molecular weights of 23 000, 8000 and 7000, respectively. With both reagents the yield of cleavage did not exceed 50%. Radioactive labeling and amino acid analysis of the purified fragments indicated the order CN1-CN2-CN3 in intact F-CB3. A shorter and apparently degraded form of F-CB3 was observed in some fibrinogen preparations. The shortening involved a region of about 3000 daltons at the N-terminal site of F-CB3, i.e. in fragment CN1.", "contents": "Disulfide-linked cyanogen bromide peptides of bovine fibrinogen. I. Isolation of peptide F-CB3 and characterization of its single disulfide bond by cleavage with cyanide. A fragment F-CB3 which originates from the alpha-chain constituent of bovine fibrinogen could be liberated by CNBr cleavage and was purified by molecular sieve and ion-exchange chromatography. This fragment had a molecular weight of 36 000 and consisted of a single polypeptide chain which is folded into a loop by a single disulfide bridge. Further cleavage of F-CB3 by cyanide or by 2-nitro-5-thiocyanobenzoic acid gave rise to three fragments, CN1, CN2 and CN3, with molecular weights of 23 000, 8000 and 7000, respectively. With both reagents the yield of cleavage did not exceed 50%. Radioactive labeling and amino acid analysis of the purified fragments indicated the order CN1-CN2-CN3 in intact F-CB3. A shorter and apparently degraded form of F-CB3 was observed in some fibrinogen preparations. The shortening involved a region of about 3000 daltons at the N-terminal site of F-CB3, i.e. in fragment CN1."} {"id": "PMID:1268219", "title": "The affinity of human, rabbit and bovine thrombins for sepharose-lysine and other conjugates.", "content": "Human, rabbit and bovine thrombins are shown to possess marked affinities for Sepharose-lysine. Using either Xa-activated crude prothrombins (human, rabbit) or a commercial thrombin sample (bovine), the enzyme was isolated in a single chromatographic step by the affinity medium and preparations of high specific activity were obtained. The relevance of bound-lysine for the affinity of the thrombins was studied using other Sepharose conjugates with structures related to Sepharose-lysine. Using freshly activated prothrombins it was found that human and rabbit thrombin uptake required a conjugate with a spacer chain containing a minimum of four carbon atoms in length which supported a terminal amino group. As the thrombin activity aged, affinity for the terminal amino group decreased but the hydrophobic spacer chain became essential for enzyme binding. The active centre of thrombin was not involved in binding to Sepharose-lysine.", "contents": "The affinity of human, rabbit and bovine thrombins for sepharose-lysine and other conjugates. Human, rabbit and bovine thrombins are shown to possess marked affinities for Sepharose-lysine. Using either Xa-activated crude prothrombins (human, rabbit) or a commercial thrombin sample (bovine), the enzyme was isolated in a single chromatographic step by the affinity medium and preparations of high specific activity were obtained. The relevance of bound-lysine for the affinity of the thrombins was studied using other Sepharose conjugates with structures related to Sepharose-lysine. Using freshly activated prothrombins it was found that human and rabbit thrombin uptake required a conjugate with a spacer chain containing a minimum of four carbon atoms in length which supported a terminal amino group. As the thrombin activity aged, affinity for the terminal amino group decreased but the hydrophobic spacer chain became essential for enzyme binding. The active centre of thrombin was not involved in binding to Sepharose-lysine."} {"id": "PMID:1268220", "title": "The aromatic residue content of the enzyme rhodanese.", "content": "The aromatic amino acid composition of the enzyme rhodanese has been redetermined. Previous reports have varied from 5 to 11 tryptophans per 26 alanine residues. The present work has quantitated the aromatic residues by a combination of amino acid analysis, solvent perturbation difference spectroscopy, specific residue modification and direct ultraviolet spectral analysis. These methods indicate that rhodanese contains 10 tyrosines, eight tryptophans and 16 phenylalanines per 26 alanine residues. The results for tyrosine and phenylalanine are in reasonable agreement with previous results.", "contents": "The aromatic residue content of the enzyme rhodanese. The aromatic amino acid composition of the enzyme rhodanese has been redetermined. Previous reports have varied from 5 to 11 tryptophans per 26 alanine residues. The present work has quantitated the aromatic residues by a combination of amino acid analysis, solvent perturbation difference spectroscopy, specific residue modification and direct ultraviolet spectral analysis. These methods indicate that rhodanese contains 10 tyrosines, eight tryptophans and 16 phenylalanines per 26 alanine residues. The results for tyrosine and phenylalanine are in reasonable agreement with previous results."} {"id": "PMID:1268221", "title": "Spectral studies of the tryptophan exposure in the enzyme rhodanese.", "content": "Tryptophan exposure in the enzyme rhodanese (thiosulfate:cyanide sulfur-transferase, EC 2.8.1.1.) has been studied by the methods of solvent perturbation difference spectroscopy, fluorescence spectroscopy and fluorescence quenching. The data from all these techniques are consistent with two classes of tryptophan:surface and buried. The surface residues appear to be relatively shielded and in an anionic environment. The buried residues have spectral characteristics suggesting they are in a very apolar environment and have less than the expected contact with the peptide backbone. The solvent perturbation difference spectra indicate further that additional tyrosine as well as tryptophan residues are buried as rhodanese is converted from the free enzyme to the sulfur-substituted enzyme: forms which are obligatory intermediates in the catalytic cycle.", "contents": "Spectral studies of the tryptophan exposure in the enzyme rhodanese. Tryptophan exposure in the enzyme rhodanese (thiosulfate:cyanide sulfur-transferase, EC 2.8.1.1.) has been studied by the methods of solvent perturbation difference spectroscopy, fluorescence spectroscopy and fluorescence quenching. The data from all these techniques are consistent with two classes of tryptophan:surface and buried. The surface residues appear to be relatively shielded and in an anionic environment. The buried residues have spectral characteristics suggesting they are in a very apolar environment and have less than the expected contact with the peptide backbone. The solvent perturbation difference spectra indicate further that additional tyrosine as well as tryptophan residues are buried as rhodanese is converted from the free enzyme to the sulfur-substituted enzyme: forms which are obligatory intermediates in the catalytic cycle."} {"id": "PMID:1268222", "title": "Cyanogen bromide fragments of bovine cervical mucus glycoprotein.", "content": "Treatment of bovine cervical mucus glycoprotein with cyanogen bromide gives four fractions, with the molecular weights of the three major fractions being 230 000, 130 000, and 35 000. The results indicate that, as for other glycoproteins, there are different regions along the protein core, some of which have a high sugar content and others which contain considerably less carbohydrate; it seems likely that the regions of lower sugar content may be important to intermolecular linkages. The data suggest that the basic unit of the glycoprotein has a molecular weight of 550 000-600 000, with its protein core consisting of approx. 1200 amino acid residues.", "contents": "Cyanogen bromide fragments of bovine cervical mucus glycoprotein. Treatment of bovine cervical mucus glycoprotein with cyanogen bromide gives four fractions, with the molecular weights of the three major fractions being 230 000, 130 000, and 35 000. The results indicate that, as for other glycoproteins, there are different regions along the protein core, some of which have a high sugar content and others which contain considerably less carbohydrate; it seems likely that the regions of lower sugar content may be important to intermolecular linkages. The data suggest that the basic unit of the glycoprotein has a molecular weight of 550 000-600 000, with its protein core consisting of approx. 1200 amino acid residues."} {"id": "PMID:1268223", "title": "Magnetic circular dichroism studies on horseradish peroxidase.", "content": "Magnetic circular dichroism (MCD) spectra were observed for native (Fe(III)) horseradish peroxidase (peroxidase, EC 1.11.1.7), its alkaline form and fluoro- and cyano-derivatives, and also for reduced (Fe(II)) horseradish peroxidase and its carbonmonoxy-- and cyano- derivatives. MCD spectra were obtained for the cyano derivative of Fe(III) horseradish peroxidase, and reduced horseradish peroxidase and its carbonmonoxy- derivative nearly identical with those for the respective myoglobin derivatives. The alkaline form of horseradish peroxidase exhibits a completely different MCD spectrum from that of myoglobin hydroxide. Thus it shows an MCD spectrum which falls into the ferric low-spin heme grouping. Native horseradish peroxidase and its fluoro derivatives show almost identical MCD spectra with those for the respective myoglobin derivatives in the visible region, though some changes were detected in the Soret region. Therefore it is concluded that the MCD spectra on the whole are sensitive to the spin state of the heme iron rather than to the porphyrin structures. The cyanide derivative of reduced horseradish peroxidase exhibited a characteristic MCD spectrum of the low-spin ferrous derivative like oxy-myoglobin.", "contents": "Magnetic circular dichroism studies on horseradish peroxidase. Magnetic circular dichroism (MCD) spectra were observed for native (Fe(III)) horseradish peroxidase (peroxidase, EC 1.11.1.7), its alkaline form and fluoro- and cyano-derivatives, and also for reduced (Fe(II)) horseradish peroxidase and its carbonmonoxy-- and cyano- derivatives. MCD spectra were obtained for the cyano derivative of Fe(III) horseradish peroxidase, and reduced horseradish peroxidase and its carbonmonoxy- derivative nearly identical with those for the respective myoglobin derivatives. The alkaline form of horseradish peroxidase exhibits a completely different MCD spectrum from that of myoglobin hydroxide. Thus it shows an MCD spectrum which falls into the ferric low-spin heme grouping. Native horseradish peroxidase and its fluoro derivatives show almost identical MCD spectra with those for the respective myoglobin derivatives in the visible region, though some changes were detected in the Soret region. Therefore it is concluded that the MCD spectra on the whole are sensitive to the spin state of the heme iron rather than to the porphyrin structures. The cyanide derivative of reduced horseradish peroxidase exhibited a characteristic MCD spectrum of the low-spin ferrous derivative like oxy-myoglobin."} {"id": "PMID:1268224", "title": "The self-association of L-alpha hydroxyacid oxidase.", "content": "As the published values for the molecular weight of L-alpha-hydroxyacid oxidase vary from 89 000 to 430 000, it is possible that such variations could be due to a concentration dependence of the molecular weight. The molecular weight of rat L-alpha-hydroxyacid oxidase was studied over a wide range of concentrations, using equilibrium sedimentation and gel exclusion chromatography. The partial specific volumes (0.726 and 0.730 for hydroxyacid oxidase A and hydroxyacid oxidase B, respectively) were calculated from the amino acid compositions, and were used to calculat molecular weights from the equilibrium sedimentation data. The molecular weight at infinite dilution was found to be 150 000 for both the A and B isozymes. Both isozymes exhibit association-dissociation behaviour at low concentrations. The self-association of the hydroxyacid oxidase B isozyme can be described by the relation (see article) where K1,2 = 5.4-10(5) M-1 and K2,4 = 1.7-10(5) M-1. Previously published values of the molecular weight of these isozymes are in accord with the observed concentration dependence.", "contents": "The self-association of L-alpha hydroxyacid oxidase. As the published values for the molecular weight of L-alpha-hydroxyacid oxidase vary from 89 000 to 430 000, it is possible that such variations could be due to a concentration dependence of the molecular weight. The molecular weight of rat L-alpha-hydroxyacid oxidase was studied over a wide range of concentrations, using equilibrium sedimentation and gel exclusion chromatography. The partial specific volumes (0.726 and 0.730 for hydroxyacid oxidase A and hydroxyacid oxidase B, respectively) were calculated from the amino acid compositions, and were used to calculat molecular weights from the equilibrium sedimentation data. The molecular weight at infinite dilution was found to be 150 000 for both the A and B isozymes. Both isozymes exhibit association-dissociation behaviour at low concentrations. The self-association of the hydroxyacid oxidase B isozyme can be described by the relation (see article) where K1,2 = 5.4-10(5) M-1 and K2,4 = 1.7-10(5) M-1. Previously published values of the molecular weight of these isozymes are in accord with the observed concentration dependence."} {"id": "PMID:1268225", "title": "Studies on the covalent structure of eland pancreatic ribonuclease.", "content": "Studies on the covalent structure of eland (Taurotragus oryx) pancreatic ribonuclease have been performed on tryptic and thermolysin digests. The first 45 residues have been determined with a Beckman sequencer. From the remaining part of the sequence only those peptides were sequenced that differed in amino acid composition with the corresponding peptide of bovine ribonuclease. Eland pancreatic ribonuclease differs in four positions from bovine pancreatic ribonuclease A, but more differences due to a different state of amidation may be present. The absence of an Asn-X-Thr/Ser sequence in the covalent structure of eland ribonuclease (asparagine 34 has been substituted by aspartic acid) explains the absence of a glycosidated component in eland ribonuclease.", "contents": "Studies on the covalent structure of eland pancreatic ribonuclease. Studies on the covalent structure of eland (Taurotragus oryx) pancreatic ribonuclease have been performed on tryptic and thermolysin digests. The first 45 residues have been determined with a Beckman sequencer. From the remaining part of the sequence only those peptides were sequenced that differed in amino acid composition with the corresponding peptide of bovine ribonuclease. Eland pancreatic ribonuclease differs in four positions from bovine pancreatic ribonuclease A, but more differences due to a different state of amidation may be present. The absence of an Asn-X-Thr/Ser sequence in the covalent structure of eland ribonuclease (asparagine 34 has been substituted by aspartic acid) explains the absence of a glycosidated component in eland ribonuclease."} {"id": "PMID:1268226", "title": "Partial structural analysis of the basic chromosomal protein of rat spermatozoa.", "content": "An investigation of the primary structure of the basic chromosomal protein of rat spermatozoa by automated Edman degradation and by carboxypeptidase digestion has provided a general structural outline of the entire molecule. The exact or approximate location of virtually all residues other than arginine or cysteine is reported. Of particular interest, because of the occurrence of phosphorylated derivatives of this protein, is the location of three of the four serine residues.", "contents": "Partial structural analysis of the basic chromosomal protein of rat spermatozoa. An investigation of the primary structure of the basic chromosomal protein of rat spermatozoa by automated Edman degradation and by carboxypeptidase digestion has provided a general structural outline of the entire molecule. The exact or approximate location of virtually all residues other than arginine or cysteine is reported. Of particular interest, because of the occurrence of phosphorylated derivatives of this protein, is the location of three of the four serine residues."} {"id": "PMID:1268227", "title": "Lactate racemase. Hydroxylamine-dependent 18O exchange of the alpha-hydroxyl of lactic acid.", "content": "The lactic acid racemase (EC 5.1.2.1) derived from Clostridium butylicum catalyzes the racemization of the alpha-18O label. The proposed alpha-carbonyl intermediate for the enzyme-catalyzed reaction has been previously shown to be trapped as an enzyme-bound oxime in the presence of hydroxylamine. This report demonstrates that the formation of the inactive enzyme-bound oxime, followed by reactivation in the presence of an excess of competing free carbonyl (pyruvic acid) results in a complete loss of the alpha-18O label from an original alpha-18O-labeled lactic acid.", "contents": "Lactate racemase. Hydroxylamine-dependent 18O exchange of the alpha-hydroxyl of lactic acid. The lactic acid racemase (EC 5.1.2.1) derived from Clostridium butylicum catalyzes the racemization of the alpha-18O label. The proposed alpha-carbonyl intermediate for the enzyme-catalyzed reaction has been previously shown to be trapped as an enzyme-bound oxime in the presence of hydroxylamine. This report demonstrates that the formation of the inactive enzyme-bound oxime, followed by reactivation in the presence of an excess of competing free carbonyl (pyruvic acid) results in a complete loss of the alpha-18O label from an original alpha-18O-labeled lactic acid."} {"id": "PMID:1268228", "title": "Studies on inosine monophosphate dehydrogenase. An associating-dissociating system.", "content": "The techniques of polyacrylamide gel electrophoresis, sedimentation velocity and frontal analysis on Sephadex have been used to demonstrate that preparations of IMP dehydrogenase (IMP: NAD+ oxidoreductase, EC 1.2.1.14) from Aerobacter aerogenes consist of a mixture of molecular weight isomers. Further, it has been shown that dissociation of the higher molecular weight forms is promoted by urea, sodium dodecyl sulphate and dithiothreitol. Under conditions comparable to those used for kinetic analyses, the enzyme has a molecular weight of about 86000 and this is the smallest active species that has been observed. In the absence of a reducing agent, the enzyme undergoes polymerization and is devoid of catalytic activity. From the amino acid composition and peptide map, it appears that the molecule with a molecular weight of 86000 is made up of two identical polypeptide chains.", "contents": "Studies on inosine monophosphate dehydrogenase. An associating-dissociating system. The techniques of polyacrylamide gel electrophoresis, sedimentation velocity and frontal analysis on Sephadex have been used to demonstrate that preparations of IMP dehydrogenase (IMP: NAD+ oxidoreductase, EC 1.2.1.14) from Aerobacter aerogenes consist of a mixture of molecular weight isomers. Further, it has been shown that dissociation of the higher molecular weight forms is promoted by urea, sodium dodecyl sulphate and dithiothreitol. Under conditions comparable to those used for kinetic analyses, the enzyme has a molecular weight of about 86000 and this is the smallest active species that has been observed. In the absence of a reducing agent, the enzyme undergoes polymerization and is devoid of catalytic activity. From the amino acid composition and peptide map, it appears that the molecule with a molecular weight of 86000 is made up of two identical polypeptide chains."} {"id": "PMID:1268229", "title": "Trimethylamine dehydrogenase from a methylotrophic bacterium. I. Isolation and steady-state kinetics.", "content": "1. The isolation of trimethylamine dehydrogenase (EC 1.5.99.7) from a restricted facultative methylotroph to electrophoretic homogeneity is described. 2. The molecular weight and subunit molecular weights were found to be 146800 for the enzyme by sedimentation equilibrium ultracentrifugation and 70000-80000 for the two non-identical subunits by sodium dodecyl sulphate gel electrophoresis. 3. Initial velocity studies indicate that the enzymatic reaction proceeds by a Ping-Pong mechanism. 4. Further kinetic evidence was obtained by analysis of product inhibition patterns using the alternate substrate diethylamine and the products acetaldehyde and ethylamine as product inhibitors, for the release of ethylamine before the addition of phenazine methosulphate and for the existence of an enzyme-two-carbon unit complex as a stable form of the enzyme. 5. Some properties of the unusual prosthetic group of trimethylamine dehydrogenase and its photodegradation product are described in preliminary form.", "contents": "Trimethylamine dehydrogenase from a methylotrophic bacterium. I. Isolation and steady-state kinetics. 1. The isolation of trimethylamine dehydrogenase (EC 1.5.99.7) from a restricted facultative methylotroph to electrophoretic homogeneity is described. 2. The molecular weight and subunit molecular weights were found to be 146800 for the enzyme by sedimentation equilibrium ultracentrifugation and 70000-80000 for the two non-identical subunits by sodium dodecyl sulphate gel electrophoresis. 3. Initial velocity studies indicate that the enzymatic reaction proceeds by a Ping-Pong mechanism. 4. Further kinetic evidence was obtained by analysis of product inhibition patterns using the alternate substrate diethylamine and the products acetaldehyde and ethylamine as product inhibitors, for the release of ethylamine before the addition of phenazine methosulphate and for the existence of an enzyme-two-carbon unit complex as a stable form of the enzyme. 5. Some properties of the unusual prosthetic group of trimethylamine dehydrogenase and its photodegradation product are described in preliminary form."} {"id": "PMID:1268230", "title": "Kinetic consequences of a slow substrate binding step in group transferases. Interpretation of product inhibition experiments.", "content": "The steady state kinetic properties of a simple model for an enzyme catalyzed group transfer reaction between two substrates have been calculated. One substrate is assumed to bind slowly and the other rapidly to the enzyme. Apparent substrate inhibition or substrate activation by the rapidly binding substrate may result if the slowly binding substrate binds at unequal rates to the free enzyme and to the complex between the enzyme and the rapidly binding substrate. Competitive inhibition by each product with respect to its structurally analogous substrate is to be expected if both substrates are in rapid equilibrium with their enzyme-substrate complexes. This product inhibition pattern, however, may also be observed when one substrate binds slowly. Noncompetitive inhibition with respect to the rapidly binding substrate by its structurally analogous product may result if the slowly binding substrate binds more slowly to the enzyme-product complex than to the free enzyme. Inhibition by substrate analogs which are not products should follow the same rules as inhibition by products. Thus substrate analog inhibition experiments are not particularly informative. The form of inhibition by \"transition state analog\" inhibitors should reveal which substrate binds slowly. There is no sharp conceptual distinction between ordered and random \"kinetic mechanisms\". I therefore suggest that the use of these concepts should be abandoned.", "contents": "Kinetic consequences of a slow substrate binding step in group transferases. Interpretation of product inhibition experiments. The steady state kinetic properties of a simple model for an enzyme catalyzed group transfer reaction between two substrates have been calculated. One substrate is assumed to bind slowly and the other rapidly to the enzyme. Apparent substrate inhibition or substrate activation by the rapidly binding substrate may result if the slowly binding substrate binds at unequal rates to the free enzyme and to the complex between the enzyme and the rapidly binding substrate. Competitive inhibition by each product with respect to its structurally analogous substrate is to be expected if both substrates are in rapid equilibrium with their enzyme-substrate complexes. This product inhibition pattern, however, may also be observed when one substrate binds slowly. Noncompetitive inhibition with respect to the rapidly binding substrate by its structurally analogous product may result if the slowly binding substrate binds more slowly to the enzyme-product complex than to the free enzyme. Inhibition by substrate analogs which are not products should follow the same rules as inhibition by products. Thus substrate analog inhibition experiments are not particularly informative. The form of inhibition by \"transition state analog\" inhibitors should reveal which substrate binds slowly. There is no sharp conceptual distinction between ordered and random \"kinetic mechanisms\". I therefore suggest that the use of these concepts should be abandoned."} {"id": "PMID:1268231", "title": "Preparation and properties of ornithine-oxo-acid aminotransferase of rat kidney. Comparison with the liver enzyme.", "content": "Ornithine-oxo-acid aminotransferase (EC 2.6.1.13) from rat kidney was prepared as a single homogeneous protein as judged by polyacrylamide gel electrophoresis, ultracentrifuge analysis and double diffusion precipitin test. Content of pyridoxal phosphate, light absorption spectra, circular dicroism spectra, Km values, inhibitors, and electrophoretic mobilities of the proteins after reactions with group modifying reagents were similar for the ornithine-oxo-acid aminotransferases of rat kidney and liver. Rates of reaction with group modifying reagents, stabilities to storage at -15 degrees C, and stabilities to temperatures above 55 degrees C differed significantly for the two enzymes. The liver enzyme contained two more cysteine residues than the kidney enzyme as determined by three different methods. Heating the liver enzyme at 66-67 degrees C at pH 5.9 for 1 h decreased the thiol groups titratable by 5,5'-dithio-bis(2-nitrobenzoic acid) (Nbs2). Uncer the same conditions titratable thiol groups of the kidney enzyme were not decreased. Amino acid analysis revealed probably significant differences in tyrosine and isoleucine content in addition to cysteine. It was concluded that the primary structures of ornithine-oxo-acid aminotransferases of rat liver and kidney are not fully identical.", "contents": "Preparation and properties of ornithine-oxo-acid aminotransferase of rat kidney. Comparison with the liver enzyme. Ornithine-oxo-acid aminotransferase (EC 2.6.1.13) from rat kidney was prepared as a single homogeneous protein as judged by polyacrylamide gel electrophoresis, ultracentrifuge analysis and double diffusion precipitin test. Content of pyridoxal phosphate, light absorption spectra, circular dicroism spectra, Km values, inhibitors, and electrophoretic mobilities of the proteins after reactions with group modifying reagents were similar for the ornithine-oxo-acid aminotransferases of rat kidney and liver. Rates of reaction with group modifying reagents, stabilities to storage at -15 degrees C, and stabilities to temperatures above 55 degrees C differed significantly for the two enzymes. The liver enzyme contained two more cysteine residues than the kidney enzyme as determined by three different methods. Heating the liver enzyme at 66-67 degrees C at pH 5.9 for 1 h decreased the thiol groups titratable by 5,5'-dithio-bis(2-nitrobenzoic acid) (Nbs2). Uncer the same conditions titratable thiol groups of the kidney enzyme were not decreased. Amino acid analysis revealed probably significant differences in tyrosine and isoleucine content in addition to cysteine. It was concluded that the primary structures of ornithine-oxo-acid aminotransferases of rat liver and kidney are not fully identical."} {"id": "PMID:1268232", "title": "Characterization of two endopolygalacturonase isozymes produced by Fusarium oxysporum f. sp. lycopersici.", "content": "Polygalacturonase (EC 3.2.1.15) produced by Fursarium oxysporum f. sp. lycopersici was purified by chromatography on DEAE-cellulose, CM-cellulose, and hydroxyapatite. The purified enzyme consisted of two electrophoretically distinct \"isozymes\", that behaved as charge isomers during electrophoresis in several different concentrations of polyacrylamide gel. The two isozymes had similar \"endo\" modes of action on polygalacturonic acid, as determined by comparison of viscosity reduction, reducing group release, and thin-layer chromatography of oligomeric hydrolysis products. Both isozymes hydrolzyed 5% of the substrate bonds in reaching 50% viscosity reduction. The amino acid compositions of the isozymes were similar and their molecular weights were about 37000 as determined by sedimentation equilibrium. Removal of large amounts of carbohydrate during purification did not affect heat stability of the enzymes. A large proportion of the remaining carbohydrate appeared to be covalently linked to the enzyme protein.", "contents": "Characterization of two endopolygalacturonase isozymes produced by Fusarium oxysporum f. sp. lycopersici. Polygalacturonase (EC 3.2.1.15) produced by Fursarium oxysporum f. sp. lycopersici was purified by chromatography on DEAE-cellulose, CM-cellulose, and hydroxyapatite. The purified enzyme consisted of two electrophoretically distinct \"isozymes\", that behaved as charge isomers during electrophoresis in several different concentrations of polyacrylamide gel. The two isozymes had similar \"endo\" modes of action on polygalacturonic acid, as determined by comparison of viscosity reduction, reducing group release, and thin-layer chromatography of oligomeric hydrolysis products. Both isozymes hydrolzyed 5% of the substrate bonds in reaching 50% viscosity reduction. The amino acid compositions of the isozymes were similar and their molecular weights were about 37000 as determined by sedimentation equilibrium. Removal of large amounts of carbohydrate during purification did not affect heat stability of the enzymes. A large proportion of the remaining carbohydrate appeared to be covalently linked to the enzyme protein."} {"id": "PMID:1268233", "title": "Specificity of acid proteinase A from Aspergillus niger var. macrosporus towards B-chain of performic acid oxidized bovine insulin.", "content": "1. A comparative study on the mode of action of two highly purified acid endopeptidases (EC 3.4.-) from Aspergillus niger var. macrosporus, acid proteinase A and B, on the B-chain of performic acid oxidized insulin was performed, putting emphasis on the quantitative analysis of the effects of enzyme A. Acid proteinase A behaved very specifically towards the substrate and hydrolyzed four peptide bonds exclusively: three major sites, where hydrolysis proceeded rapidly and almost completely, Asn3-Gln4, Glu13-Ala14, and Tyr26-Thr27; and a minor one, Gly20-Glu21, at which hydrolysis was much slower. 2. The effects of four protease inhibitors, pepstatin, diazoacetyl-D,L-norleucine methyl ester/Cu(II), di-isopropyl phosphorofluoridate, and 1,2-epoxy-3-(p-nitrophenozy) propane on acid proteinases A and B were studied. Acid proteinase A preparations, treated with the former two inhibitors, were used to establish that the major sites of attack were really affected by enzyme A and not by contaminating proteinase B.", "contents": "Specificity of acid proteinase A from Aspergillus niger var. macrosporus towards B-chain of performic acid oxidized bovine insulin. 1. A comparative study on the mode of action of two highly purified acid endopeptidases (EC 3.4.-) from Aspergillus niger var. macrosporus, acid proteinase A and B, on the B-chain of performic acid oxidized insulin was performed, putting emphasis on the quantitative analysis of the effects of enzyme A. Acid proteinase A behaved very specifically towards the substrate and hydrolyzed four peptide bonds exclusively: three major sites, where hydrolysis proceeded rapidly and almost completely, Asn3-Gln4, Glu13-Ala14, and Tyr26-Thr27; and a minor one, Gly20-Glu21, at which hydrolysis was much slower. 2. The effects of four protease inhibitors, pepstatin, diazoacetyl-D,L-norleucine methyl ester/Cu(II), di-isopropyl phosphorofluoridate, and 1,2-epoxy-3-(p-nitrophenozy) propane on acid proteinases A and B were studied. Acid proteinase A preparations, treated with the former two inhibitors, were used to establish that the major sites of attack were really affected by enzyme A and not by contaminating proteinase B."} {"id": "PMID:1268234", "title": "Characterization of agarose-bound trypsin.", "content": "Agarose-bound trypsin (EC 3.4.21.4) was prepared and its properties were compared with those of soluble trypsin. The bound form of the enzyme was found to be equally available to large and small molecular weight substrates as the soluble form. In addition, the bound form of the enzyme showed the same specificity towards protein substrates as the soluble enzyme. However, the agarose-bound trypsin showed greater stability than the soluble trypsin to denaturing conditions for prolonged period of time.", "contents": "Characterization of agarose-bound trypsin. Agarose-bound trypsin (EC 3.4.21.4) was prepared and its properties were compared with those of soluble trypsin. The bound form of the enzyme was found to be equally available to large and small molecular weight substrates as the soluble form. In addition, the bound form of the enzyme showed the same specificity towards protein substrates as the soluble enzyme. However, the agarose-bound trypsin showed greater stability than the soluble trypsin to denaturing conditions for prolonged period of time."} {"id": "PMID:1268235", "title": "Phosphatidyl-(N-acyl)-ethanolamine. A lipid component of mammalian epidermis.", "content": "A lipid present in the granular cells of mammalian epidermis was identified as phosphatidyl-(N-acyl)-ethanolamine. The structure was deduced from the ratio of phosphorus : nitrogen : glycerol : fatty acid esters : total fatty acid (1 : 0.94 : 0.97 : 2.1 : 2.9), from analyses of the products of alkaline and acid hydrolyses and from its infrared spectrum. Conclusive evidence was obtained by a direct comparison of the chromatographic properties, degradation products and infrared spectrum of the isolated lipid with those of synthetic 1,2-dipalmitoyl-sn-glycero-3-phospho-(N-palmitoyl)-ethanolamine. The fatty acids attached to the ethanolamine were predominantly saturated (69% of total) and hexadecanoic acid was the major component (41% of total). Phosphatidyl-(N-acyl)-ethanolamine was hydrolysed by a phospholipase C (Bacillus cereus) to diacylglycerol, inorganic phosphorus and N-acylethanolamine. Evidence for the presence of N-acylethanolamine in granular cells and in stratum corneum suggested that an epidermal phospholipase C may be involved in the catabolism of phosphatidyl-(N-acyl)-ethanolamine.", "contents": "Phosphatidyl-(N-acyl)-ethanolamine. A lipid component of mammalian epidermis. A lipid present in the granular cells of mammalian epidermis was identified as phosphatidyl-(N-acyl)-ethanolamine. The structure was deduced from the ratio of phosphorus : nitrogen : glycerol : fatty acid esters : total fatty acid (1 : 0.94 : 0.97 : 2.1 : 2.9), from analyses of the products of alkaline and acid hydrolyses and from its infrared spectrum. Conclusive evidence was obtained by a direct comparison of the chromatographic properties, degradation products and infrared spectrum of the isolated lipid with those of synthetic 1,2-dipalmitoyl-sn-glycero-3-phospho-(N-palmitoyl)-ethanolamine. The fatty acids attached to the ethanolamine were predominantly saturated (69% of total) and hexadecanoic acid was the major component (41% of total). Phosphatidyl-(N-acyl)-ethanolamine was hydrolysed by a phospholipase C (Bacillus cereus) to diacylglycerol, inorganic phosphorus and N-acylethanolamine. Evidence for the presence of N-acylethanolamine in granular cells and in stratum corneum suggested that an epidermal phospholipase C may be involved in the catabolism of phosphatidyl-(N-acyl)-ethanolamine."} {"id": "PMID:1268236", "title": "Biochemical studies on the cell wall lipopolysaccharides (O-antigens) of Vibrio cholerae 569 B (Inaba) and El-tor (Inaba).", "content": "Lipopolysaccharides were isolated from the cell walls of Vibrio cholerae 569 B (Inaba) and El-tor (Inaba). Chemical analysis revealed the presence of glucose, fructose, mannose, heptose, rhamnose, ethanolamine, fatty acids and glucosamine. The lipopolysaccharides do not contain 2-keto-3-deoxyoctonate, the typical linking sugar of polysaccharide and lipid moieties of enterobacterial lipopolysaccharides. Galactose, a typical core polysaccharide component of many gram-negative bacteria was also absent from lipopolysaccharides of these organisms. By hydrolysis in 1% acetic acid, the lipopolysaccharides have been separated into a polysaccharide part (degraded polysaccharide) and a lipid part (lipid A). Components of degraded polysaccharide and lipid A moiety were identified and determined. The lipid A fractions contained fatty acids, phosphorus and glucosamine. All the neutral sugars detected in lipopolysaccharides were shown to be the constituents of its polysaccharide moiety. The fatty acid analysis of lipopolysaccharide and lipid A showed the presence of both hydroxy and non hydroxy acids. They were different from those of lipids extracted from cell walls before the extraction of lipopolysaccharides. 3-Hydroxylauric and 3-hydroxymyristic acids predominated in lipopolysaccharide and lipid A of Vibrio cholerae and El-tor (Inaba).", "contents": "Biochemical studies on the cell wall lipopolysaccharides (O-antigens) of Vibrio cholerae 569 B (Inaba) and El-tor (Inaba). Lipopolysaccharides were isolated from the cell walls of Vibrio cholerae 569 B (Inaba) and El-tor (Inaba). Chemical analysis revealed the presence of glucose, fructose, mannose, heptose, rhamnose, ethanolamine, fatty acids and glucosamine. The lipopolysaccharides do not contain 2-keto-3-deoxyoctonate, the typical linking sugar of polysaccharide and lipid moieties of enterobacterial lipopolysaccharides. Galactose, a typical core polysaccharide component of many gram-negative bacteria was also absent from lipopolysaccharides of these organisms. By hydrolysis in 1% acetic acid, the lipopolysaccharides have been separated into a polysaccharide part (degraded polysaccharide) and a lipid part (lipid A). Components of degraded polysaccharide and lipid A moiety were identified and determined. The lipid A fractions contained fatty acids, phosphorus and glucosamine. All the neutral sugars detected in lipopolysaccharides were shown to be the constituents of its polysaccharide moiety. The fatty acid analysis of lipopolysaccharide and lipid A showed the presence of both hydroxy and non hydroxy acids. They were different from those of lipids extracted from cell walls before the extraction of lipopolysaccharides. 3-Hydroxylauric and 3-hydroxymyristic acids predominated in lipopolysaccharide and lipid A of Vibrio cholerae and El-tor (Inaba)."} {"id": "PMID:1268237", "title": "Relationship between prostaglandin biosynthesis and the effect of insulin on hormone-stimulated lipolysis in rat adipose tissue.", "content": "Lipolysis in rat fat pads was studied by determination of free fatty acid and glycerol production in various experimental conditions (in the absence or presence of glucose, adrenalin and insulin). These results were compared to the accumulation of endogenous prostaglandins E2 and F2alpha during lipolysis. In the absence of glucose the prostaglandin production followed the adrenalin-induced fluctuations in released free fatty acids both in the presence or absence of insulin. In the presence of glucose and insulin, a drop in prostaglandin accumulation was observed whereas free fatty acids production was strongly stimulated. These results suggest that either free fatty acid composition is modified, influencing the activity of prostaglandin synthetase, or that there exists a specific mechanism controlling prostaglandin synthesis.", "contents": "Relationship between prostaglandin biosynthesis and the effect of insulin on hormone-stimulated lipolysis in rat adipose tissue. Lipolysis in rat fat pads was studied by determination of free fatty acid and glycerol production in various experimental conditions (in the absence or presence of glucose, adrenalin and insulin). These results were compared to the accumulation of endogenous prostaglandins E2 and F2alpha during lipolysis. In the absence of glucose the prostaglandin production followed the adrenalin-induced fluctuations in released free fatty acids both in the presence or absence of insulin. In the presence of glucose and insulin, a drop in prostaglandin accumulation was observed whereas free fatty acids production was strongly stimulated. These results suggest that either free fatty acid composition is modified, influencing the activity of prostaglandin synthetase, or that there exists a specific mechanism controlling prostaglandin synthesis."} {"id": "PMID:1268238", "title": "125I derivatives of prostaglandins. A novel approach in prostaglandin analysis by radioimmunoassay.", "content": "We report the production of radioactive iodinated (125 I) derivatives of prostaglandins E1, E2, F2alpha and their use in radioimmunological assays. Histamine or tyramine was coupled to the prostaglandins carboxyl group and the iodination was accomplished using the chloramine T method. The high specific radioactivity of these tracers and the resolution of the purification procedure allowed the detection of 0.5 pg of prostaglandins. A comparison with tritiated prostaglandin was made and showed a 10-fold gain in sensitivity. Furthermore in the case of the prostaglandin E1 system using 125I-labelled histamine or tyramine as tracer the cross reaction curves obtained were different from those obtained with [3H]prostaglandin E1; we suggest that the blocking of the carboxyl group alters the prostaglandin E1 structure, modifying its immunoreactivity.", "contents": "125I derivatives of prostaglandins. A novel approach in prostaglandin analysis by radioimmunoassay. We report the production of radioactive iodinated (125 I) derivatives of prostaglandins E1, E2, F2alpha and their use in radioimmunological assays. Histamine or tyramine was coupled to the prostaglandins carboxyl group and the iodination was accomplished using the chloramine T method. The high specific radioactivity of these tracers and the resolution of the purification procedure allowed the detection of 0.5 pg of prostaglandins. A comparison with tritiated prostaglandin was made and showed a 10-fold gain in sensitivity. Furthermore in the case of the prostaglandin E1 system using 125I-labelled histamine or tyramine as tracer the cross reaction curves obtained were different from those obtained with [3H]prostaglandin E1; we suggest that the blocking of the carboxyl group alters the prostaglandin E1 structure, modifying its immunoreactivity."} {"id": "PMID:1268239", "title": "Intra- and extracellular forms of lipoprotein lipase in adipose tissue.", "content": "The location of lipoprotein lipase activity in rat adipose tissue was studied using intact epididymal fat pads, isolated adipocytes, and lipoprotein lipase activity secreted from adipocytes as enzyme sources. The enzyme activities of these preparations were characterized by gel filtration. The method used for isolation of adipocytes had been modified to minimize activation of lipoprotein lipase during the procedures. Extracts of intact adipose tissue separated into two major lipoprotein lipase activity peaks, designated \"a\" and \"b\", the \"a\" fraction representing about 30 (fasted rats) to 50% (fed rats) of the total enzyme activity. An intermediate fraction (designated \"i\") was frequently observed. Extracts of isolated adipocytes from fed rats contained about 35% and those from fasted rats about 65% of the lipoprotein lipase activity present in intact tissue. The \"b\" fraction constituted 80--97% of the adipocyte lipoprotein lipase activity. In contrast, the enzyme activity secreted from the adipocytes contained only the \"a\" and \"i\" fractions. These data implicate the existance of one intracellular form of lipoprotein lipase (corresponding to the \"b\" fraction), different from extracellular forms of the enzyme (corresponding to fractions \"a\" and \"i\"). A transformation of the intracellular to the extracellular forms appears to occur in conjunction with secretion of enzyme from the fat cell.", "contents": "Intra- and extracellular forms of lipoprotein lipase in adipose tissue. The location of lipoprotein lipase activity in rat adipose tissue was studied using intact epididymal fat pads, isolated adipocytes, and lipoprotein lipase activity secreted from adipocytes as enzyme sources. The enzyme activities of these preparations were characterized by gel filtration. The method used for isolation of adipocytes had been modified to minimize activation of lipoprotein lipase during the procedures. Extracts of intact adipose tissue separated into two major lipoprotein lipase activity peaks, designated \"a\" and \"b\", the \"a\" fraction representing about 30 (fasted rats) to 50% (fed rats) of the total enzyme activity. An intermediate fraction (designated \"i\") was frequently observed. Extracts of isolated adipocytes from fed rats contained about 35% and those from fasted rats about 65% of the lipoprotein lipase activity present in intact tissue. The \"b\" fraction constituted 80--97% of the adipocyte lipoprotein lipase activity. In contrast, the enzyme activity secreted from the adipocytes contained only the \"a\" and \"i\" fractions. These data implicate the existance of one intracellular form of lipoprotein lipase (corresponding to the \"b\" fraction), different from extracellular forms of the enzyme (corresponding to fractions \"a\" and \"i\"). A transformation of the intracellular to the extracellular forms appears to occur in conjunction with secretion of enzyme from the fat cell."} {"id": "PMID:1268240", "title": "The age-related occurrence of wax esters in the mouse preputial gland tumour.", "content": "The mouse preputial gland tumour (ESR-586) accumulates wax esters from between 20 and 25 days after transplantation until they become the most abundant lipid class. Prior to this time wax esters are not detectable. The process occurs in both male and female host mice and appears to be determined by a response of the host to the tumour, rather than by a property of the tumour itself. The most abundant fatty alcohol present in the wax esters is hexadecanol. This contrasts with the greater proportions of the C20 to C24 chains found for the alkyl portion of the alkyldiacylglycerols, for which the precursors are fatty alcohols.", "contents": "The age-related occurrence of wax esters in the mouse preputial gland tumour. The mouse preputial gland tumour (ESR-586) accumulates wax esters from between 20 and 25 days after transplantation until they become the most abundant lipid class. Prior to this time wax esters are not detectable. The process occurs in both male and female host mice and appears to be determined by a response of the host to the tumour, rather than by a property of the tumour itself. The most abundant fatty alcohol present in the wax esters is hexadecanol. This contrasts with the greater proportions of the C20 to C24 chains found for the alkyl portion of the alkyldiacylglycerols, for which the precursors are fatty alcohols."} {"id": "PMID:1268241", "title": "Synthesis of anacardic acids in seeds of Ginkgo biloba.", "content": "Anacardic (6-alkylsalicylic) acids and common lipids are efficiently synthesized by immature seeds of Ginkgo biloba. The seeds were incubated with 14C-labeled acetic, malonic and palmitoleic acids, glucose, and other potential precursors. Levels of 14C in common lipids and in anacardic acids, and the distribution of 14C in anacardic acids were determined. The results show that the salicylic moiety is synthesized by a polyketide pathway via malonic acid. The chain moiety for anacardic acid synthesis is in a different state of activation and/or site than chains that are used for synthesis of the common lipids. Labeled shikimic acid did not contribute 14C to anacardic acids, nor to other lipids, and palmitoleic acid was incorporated only into common lipids.", "contents": "Synthesis of anacardic acids in seeds of Ginkgo biloba. Anacardic (6-alkylsalicylic) acids and common lipids are efficiently synthesized by immature seeds of Ginkgo biloba. The seeds were incubated with 14C-labeled acetic, malonic and palmitoleic acids, glucose, and other potential precursors. Levels of 14C in common lipids and in anacardic acids, and the distribution of 14C in anacardic acids were determined. The results show that the salicylic moiety is synthesized by a polyketide pathway via malonic acid. The chain moiety for anacardic acid synthesis is in a different state of activation and/or site than chains that are used for synthesis of the common lipids. Labeled shikimic acid did not contribute 14C to anacardic acids, nor to other lipids, and palmitoleic acid was incorporated only into common lipids."} {"id": "PMID:1268242", "title": "Isomerization of prostaglandin H2 into prostaglandin D2 in the presence of serum albumin.", "content": "The prostaglandin endoperoxide, prostaglandin H2, decomposes in aqueous media mainly into prostaglandin E2. This paper shows that in the presence of serum albumin from a number of species prostaglandin H2 decomposes mainly into prostaglandin D2, an isomer of prostaglandin E2. The effect on endoperoxide decomposition exerted by serum albumin may well have physiological significance since intace endoperoxides can be released from tissues and since the biological properties of prostaglandins E2 and D2 are quite different.", "contents": "Isomerization of prostaglandin H2 into prostaglandin D2 in the presence of serum albumin. The prostaglandin endoperoxide, prostaglandin H2, decomposes in aqueous media mainly into prostaglandin E2. This paper shows that in the presence of serum albumin from a number of species prostaglandin H2 decomposes mainly into prostaglandin D2, an isomer of prostaglandin E2. The effect on endoperoxide decomposition exerted by serum albumin may well have physiological significance since intace endoperoxides can be released from tissues and since the biological properties of prostaglandins E2 and D2 are quite different."} {"id": "PMID:1268243", "title": "Metabolism of erucic acid in the isolated perfused rat heart.", "content": "In the present work the uptake and utilization of [14C]erucic acid by the perfused rat heart has been investigated and compared with those of [14C]-palmitic acid. Both fatty acids were found to be taken up by the heart at the same rate. On the other hand, the incorporation of erucic acid into tissue lipid during 30 min perfusion were significantly high and CO2 production low as compared with palmitic acid. Incorporation of erucic acid into diacylglycerol, triacylglycerol and cholesterol ester was considerably higher than that of palmitic acid. During a 30-min period, a large amount of [14C]erucic acid was accumulated in tissue fatty acid fraction. Similarly, relatively high labelling was found in the fatty acid and diacylglycerol fraction during the initial 300 s of perfusion with erucic acid. When [14C]erucic acid and unlabelled palmitic acid was used, the radioactivity was very high in the fatty acid fraction of the heart lipid in comparison with the experiment when [14C]palmitate and unlabelled erucic acid was used. Therefore, erucic acid is poorly oxidized by the heart and is preferentially incorporated into heart lipids. There was relatively high incorporation of [14C]erucic acid into diacylglycerol and addition of unlabelled palmitic acid tended to decrease it, probably converting more diacylglycerol to triacylglycerol. When [14C]palmitic acid and erucic acid were used together, incorporation to triacylglycerol was high and diacylglycerol low. These results, therefore suggest that palmitic acid is a more suitable acyl donor than erucic acid for the C-3 position of triacylglycerol, especially when the diacylglycerol contains erucoyl moieties.", "contents": "Metabolism of erucic acid in the isolated perfused rat heart. In the present work the uptake and utilization of [14C]erucic acid by the perfused rat heart has been investigated and compared with those of [14C]-palmitic acid. Both fatty acids were found to be taken up by the heart at the same rate. On the other hand, the incorporation of erucic acid into tissue lipid during 30 min perfusion were significantly high and CO2 production low as compared with palmitic acid. Incorporation of erucic acid into diacylglycerol, triacylglycerol and cholesterol ester was considerably higher than that of palmitic acid. During a 30-min period, a large amount of [14C]erucic acid was accumulated in tissue fatty acid fraction. Similarly, relatively high labelling was found in the fatty acid and diacylglycerol fraction during the initial 300 s of perfusion with erucic acid. When [14C]erucic acid and unlabelled palmitic acid was used, the radioactivity was very high in the fatty acid fraction of the heart lipid in comparison with the experiment when [14C]palmitate and unlabelled erucic acid was used. Therefore, erucic acid is poorly oxidized by the heart and is preferentially incorporated into heart lipids. There was relatively high incorporation of [14C]erucic acid into diacylglycerol and addition of unlabelled palmitic acid tended to decrease it, probably converting more diacylglycerol to triacylglycerol. When [14C]palmitic acid and erucic acid were used together, incorporation to triacylglycerol was high and diacylglycerol low. These results, therefore suggest that palmitic acid is a more suitable acyl donor than erucic acid for the C-3 position of triacylglycerol, especially when the diacylglycerol contains erucoyl moieties."} {"id": "PMID:1268244", "title": "Effects of detergents and choline-containing phospholipids on human spleen glucocerebrosidase.", "content": "1. Glucocerebrosidase, extracted from human spleen lysosomal membrane by sodium cholate and recovered in a high speed centrifugation supernatant, aggregated following removal of the detergent. 2. Re-solubilization of the enzymatic activity from the aggregate was achieved by treatment with the non-ionic detergents Triton X-100 and Tween 20. The anionic detergents sodium cholate and sodium taurocholate and the cationic detergents cetyltrimethylammonium bromide and cetylpyridinium chloride were also effective. The solubilizing capacity of the anionic detergents was smaller than that of the nonionic detergents. Quantitative evaluation of the solubilizing capacity of the cationic detergents was not feasible because of their being potent inhibitors of glucocerebrosidase activity. 3. Treatment of the enzyme aggregate with acetone rendered it buffer-soluble. 4. In addition to the above cationic detergents some choline-containing and highly hydrophobic phospholipids were found to inhibit the glucocerebrosidase activity.", "contents": "Effects of detergents and choline-containing phospholipids on human spleen glucocerebrosidase. 1. Glucocerebrosidase, extracted from human spleen lysosomal membrane by sodium cholate and recovered in a high speed centrifugation supernatant, aggregated following removal of the detergent. 2. Re-solubilization of the enzymatic activity from the aggregate was achieved by treatment with the non-ionic detergents Triton X-100 and Tween 20. The anionic detergents sodium cholate and sodium taurocholate and the cationic detergents cetyltrimethylammonium bromide and cetylpyridinium chloride were also effective. The solubilizing capacity of the anionic detergents was smaller than that of the nonionic detergents. Quantitative evaluation of the solubilizing capacity of the cationic detergents was not feasible because of their being potent inhibitors of glucocerebrosidase activity. 3. Treatment of the enzyme aggregate with acetone rendered it buffer-soluble. 4. In addition to the above cationic detergents some choline-containing and highly hydrophobic phospholipids were found to inhibit the glucocerebrosidase activity."} {"id": "PMID:1268245", "title": "Studies on lysophospholipases. VI. The action of two purified lysophospholipases from beef liver on membrane-bound lysophosphatidylcholine.", "content": "The action of two lysophospholipases purified from beef liver on lysophosphatidylcholine in microsomal membranes has been studied. Enzyme I, which has been shown to be localized in the soluble fraction of the beef liver cell, has a higher specific activity on microsomal lysophosphatidylcholine than Enzyme II, which originates from the microsomal cell fraction. This trend is also observed with phosphatidylcholine liposomes and single bilayer vesicles in which lysophosphatidylcholine has been incorporated. At low mol fractions of lysophosphatidylcholine in liposomes, the maximum enzymatic rate is proportional to this mol fraction. Similar results are obtained with mixed micelles of lysophosphatidylcholine and Triton X-100. The results are explained in terms of a model in which the two-dimensional substrate density in the membrane surface controls the rate of enzyme action.", "contents": "Studies on lysophospholipases. VI. The action of two purified lysophospholipases from beef liver on membrane-bound lysophosphatidylcholine. The action of two lysophospholipases purified from beef liver on lysophosphatidylcholine in microsomal membranes has been studied. Enzyme I, which has been shown to be localized in the soluble fraction of the beef liver cell, has a higher specific activity on microsomal lysophosphatidylcholine than Enzyme II, which originates from the microsomal cell fraction. This trend is also observed with phosphatidylcholine liposomes and single bilayer vesicles in which lysophosphatidylcholine has been incorporated. At low mol fractions of lysophosphatidylcholine in liposomes, the maximum enzymatic rate is proportional to this mol fraction. Similar results are obtained with mixed micelles of lysophosphatidylcholine and Triton X-100. The results are explained in terms of a model in which the two-dimensional substrate density in the membrane surface controls the rate of enzyme action."} {"id": "PMID:1268246", "title": "Is phospholipase D really an enzyme? A comparison of in situ and in vitro activities.", "content": "Leaf phospholipase D activity was compared in vitro and in situ. In the in situ reaction stimulated by methanol only phosphatidylcholine and phosphatidylethanolamine were degraded until approx. 80% of these endogenous substrates had been consumed. Only then was a limited amount (approx. 20%) of endogenous phosphatidylglycerol degraded. Endogenous phosphatidylinositol was apparently not susceptible to phospholipase D in situ. In the vitro reaction the relative susceptibilities to degradation of added phospholipid substrates were (a) in the absence of \"activators\" phosphatidylethanolamine greater than phosphatidylglycerol greater than phosphatidylcholine, (b) in the presence of diethyl ether phosphatidylcholine greater than phosphatidylethanolamine greater than phosphatidylglycerol and (c) in the presence of sodium dodecyl sulphate phosphatidylcholine greater than phosphatidylethanolamine = phosphatidylglycerol. Minimum rates calculated for the in situ reaction in cauliflower leaf were 5-fold higher than maximum in vitro rates reported for the same material. Phospholipase D activity has been demonstrated by the in situ reaction in all leaf tissue so far examined. From these data we conclude that phospholipase D may be an integral part of membranes containing phosphatidylcholine and phosphatidylethanolamine, but not of membranes containing phosphatidylglycerol. We also suggest that phospholipase D may not be a physiological enzyme, but rather a structural protein of phosphatidylcholine- and phosphatidylethanolamine-containing membranes and which, under certain non-physiological conditions, possess enzymic properties.", "contents": "Is phospholipase D really an enzyme? A comparison of in situ and in vitro activities. Leaf phospholipase D activity was compared in vitro and in situ. In the in situ reaction stimulated by methanol only phosphatidylcholine and phosphatidylethanolamine were degraded until approx. 80% of these endogenous substrates had been consumed. Only then was a limited amount (approx. 20%) of endogenous phosphatidylglycerol degraded. Endogenous phosphatidylinositol was apparently not susceptible to phospholipase D in situ. In the vitro reaction the relative susceptibilities to degradation of added phospholipid substrates were (a) in the absence of \"activators\" phosphatidylethanolamine greater than phosphatidylglycerol greater than phosphatidylcholine, (b) in the presence of diethyl ether phosphatidylcholine greater than phosphatidylethanolamine greater than phosphatidylglycerol and (c) in the presence of sodium dodecyl sulphate phosphatidylcholine greater than phosphatidylethanolamine = phosphatidylglycerol. Minimum rates calculated for the in situ reaction in cauliflower leaf were 5-fold higher than maximum in vitro rates reported for the same material. Phospholipase D activity has been demonstrated by the in situ reaction in all leaf tissue so far examined. From these data we conclude that phospholipase D may be an integral part of membranes containing phosphatidylcholine and phosphatidylethanolamine, but not of membranes containing phosphatidylglycerol. We also suggest that phospholipase D may not be a physiological enzyme, but rather a structural protein of phosphatidylcholine- and phosphatidylethanolamine-containing membranes and which, under certain non-physiological conditions, possess enzymic properties."} {"id": "PMID:1268247", "title": "In vivo metabolism of labeled oleic and linoleic acids by the laying hen.", "content": "Radioactive oleic and linoleic acids, labeled with 3H in the chain and 14C in the carbonyl group, were administered to white leghorn laying hens. Mixtures fed in separate experiments included: (1) 3H- and 14C-labeled oleic acid, (2) 3H- and 14C-labeled linoleic acid and (3) [3H]oleic aicd and [14C] linoleic acid. The 3H/14C ratios of both the neutral lipid and phospholipid fractions from the egg yolk and of the isolated acids from these lipid fractions were compared to that in the administered mixture. Agreement in the 3H/14C ratios for the neutral lipid fraction from each of the feeding experiments indicated that neither the 3H- and 14C labeled acids nor the oleic or linoleic acids were distinguishable during synthesis of the neutral lipid. Analysis of the phospholipid fractions showed that when dual-labeled mixtures of oleic acid were administered, 3H/14C ratios were elevated and, therefore, there was selective elimination of the 14C label. When dual-labeled mixtures of linoleic acid were administered, the 3H/14C ratios were in agreement; and when the two acids were administered simultaneously as a dual-labeled mixture, there was selective incorporation of linoleic acid. These findings indicate separate metabolic pathways for synthesis of neutral lipid and phospholipid in egg yolk as expected, as well as preferential use of the essential fatty acid in the phospholipid by the hen.", "contents": "In vivo metabolism of labeled oleic and linoleic acids by the laying hen. Radioactive oleic and linoleic acids, labeled with 3H in the chain and 14C in the carbonyl group, were administered to white leghorn laying hens. Mixtures fed in separate experiments included: (1) 3H- and 14C-labeled oleic acid, (2) 3H- and 14C-labeled linoleic acid and (3) [3H]oleic aicd and [14C] linoleic acid. The 3H/14C ratios of both the neutral lipid and phospholipid fractions from the egg yolk and of the isolated acids from these lipid fractions were compared to that in the administered mixture. Agreement in the 3H/14C ratios for the neutral lipid fraction from each of the feeding experiments indicated that neither the 3H- and 14C labeled acids nor the oleic or linoleic acids were distinguishable during synthesis of the neutral lipid. Analysis of the phospholipid fractions showed that when dual-labeled mixtures of oleic acid were administered, 3H/14C ratios were elevated and, therefore, there was selective elimination of the 14C label. When dual-labeled mixtures of linoleic acid were administered, the 3H/14C ratios were in agreement; and when the two acids were administered simultaneously as a dual-labeled mixture, there was selective incorporation of linoleic acid. These findings indicate separate metabolic pathways for synthesis of neutral lipid and phospholipid in egg yolk as expected, as well as preferential use of the essential fatty acid in the phospholipid by the hen."} {"id": "PMID:1268248", "title": "Methylation analysis of the major gangliosides of the human alimentary mucosa.", "content": "The five major gangliosides of the human alimentary mucosa were purified with silicic acid column chromatography and with thin-layer chromatography. The linkages in the carbohydrate portion were analysed by permethylation with gas chromatography-mass spectrometry. A succesful analysis of the linkages of two hematosides and three tetraglycosylceramides was performed. Two of the tetraglycosylamides had a galactosamine in their chain and one had a glucosamine.", "contents": "Methylation analysis of the major gangliosides of the human alimentary mucosa. The five major gangliosides of the human alimentary mucosa were purified with silicic acid column chromatography and with thin-layer chromatography. The linkages in the carbohydrate portion were analysed by permethylation with gas chromatography-mass spectrometry. A succesful analysis of the linkages of two hematosides and three tetraglycosylceramides was performed. Two of the tetraglycosylamides had a galactosamine in their chain and one had a glucosamine."} {"id": "PMID:1268249", "title": "DNA sequence repetition in the genome of the American oyster.", "content": "The genome of Crassostrea virignica, the American oyster, has been studied by reassociation kinetics in order to construct a profile of DNA sequence frequency components. Oyster DNA has been shown to contain at least 51% single copy DNA sequences and two classes of middle repetitive DNA. The major repetitive class contains sequences which are repeated on the average 20 times and comprise 29% of oyster DNA. The other class represents 10% of oyster DNA and contains sequences repeated approx. 3000 times. In addition the DNA of oyster contains at least 1% foldback sequences. The spectrum of DNA repetition components in the American oyster is similar to that found in the genomes of other mollusks.", "contents": "DNA sequence repetition in the genome of the American oyster. The genome of Crassostrea virignica, the American oyster, has been studied by reassociation kinetics in order to construct a profile of DNA sequence frequency components. Oyster DNA has been shown to contain at least 51% single copy DNA sequences and two classes of middle repetitive DNA. The major repetitive class contains sequences which are repeated on the average 20 times and comprise 29% of oyster DNA. The other class represents 10% of oyster DNA and contains sequences repeated approx. 3000 times. In addition the DNA of oyster contains at least 1% foldback sequences. The spectrum of DNA repetition components in the American oyster is similar to that found in the genomes of other mollusks."} {"id": "PMID:1268250", "title": "Interspersion and transcription of repeated sequences of rat DNA.", "content": "Repetitive rat DNA reassociated to Cot=0.1 and deprived of \"foldback\" sequences showed close interspersion with unique sequences. As measured by electron microscopy, the average length of repetitive segments was about 600 +/- 400, and of unique segments 1800-3600 base pairs. Pyrimidine tracts over 80 nucleotides in length were found mainly in foldback and repetitive fractions. Oligo(dT) tracts, 20-30 bases in length prevailed in the DNA fraction reassociated to Cot=0.1. Repetitive and unique DNA fractions were annealed to Millipore filters and hybridized with hnRNA. Up to 1.6% of repetitive DNA reassociated to Cot=0.05 showed base complementarity with hnRNA, whereas the comparative figures for DNA reassociated to Cot=10 and for the unique fraction were 0.8% and 0.3% respectively. When hybridization of hnRNA was carried out in solution in vast DNA excess, no hybrid formation with repetitive sequences reassociated to Cot=0.1 was observed, although hybridization with DNA reassociated to Cot=10 was noticeable.", "contents": "Interspersion and transcription of repeated sequences of rat DNA. Repetitive rat DNA reassociated to Cot=0.1 and deprived of \"foldback\" sequences showed close interspersion with unique sequences. As measured by electron microscopy, the average length of repetitive segments was about 600 +/- 400, and of unique segments 1800-3600 base pairs. Pyrimidine tracts over 80 nucleotides in length were found mainly in foldback and repetitive fractions. Oligo(dT) tracts, 20-30 bases in length prevailed in the DNA fraction reassociated to Cot=0.1. Repetitive and unique DNA fractions were annealed to Millipore filters and hybridized with hnRNA. Up to 1.6% of repetitive DNA reassociated to Cot=0.05 showed base complementarity with hnRNA, whereas the comparative figures for DNA reassociated to Cot=10 and for the unique fraction were 0.8% and 0.3% respectively. When hybridization of hnRNA was carried out in solution in vast DNA excess, no hybrid formation with repetitive sequences reassociated to Cot=0.1 was observed, although hybridization with DNA reassociated to Cot=10 was noticeable."} {"id": "PMID:1268251", "title": "Specific ribonucleoprotein fragments from 40-S ribosomal subunits.", "content": "Well-defined ribonucleoprotein fragments, resulting from the action of endogenous nuclease on 40-S subunits, were able to be separated when using high concentrations of LiCl. The ribonucleoproteins obtained sedimented at 12, 17 S, 23 S and 30 S and contained 8 S, 12 S and 17 S RNA, respectively, associated with a few proteins. The proteins extracted from the fragments were [3H] labeled by reductive methylation and their molar proportion was determined. The smallest fragment (12, 17 S) contained only three proteins, S8, S9 and S24. The 23-S and 30-S materials contained some proteins in common, S15, S19, S22, S25; S16 was found mainly in 30 S. Two proteins, S26 and \"protein y\" were found mainly in 23 S material. Thus, these results can give information on the relative location of certain proteins in the 40-S subunits.", "contents": "Specific ribonucleoprotein fragments from 40-S ribosomal subunits. Well-defined ribonucleoprotein fragments, resulting from the action of endogenous nuclease on 40-S subunits, were able to be separated when using high concentrations of LiCl. The ribonucleoproteins obtained sedimented at 12, 17 S, 23 S and 30 S and contained 8 S, 12 S and 17 S RNA, respectively, associated with a few proteins. The proteins extracted from the fragments were [3H] labeled by reductive methylation and their molar proportion was determined. The smallest fragment (12, 17 S) contained only three proteins, S8, S9 and S24. The 23-S and 30-S materials contained some proteins in common, S15, S19, S22, S25; S16 was found mainly in 30 S. Two proteins, S26 and \"protein y\" were found mainly in 23 S material. Thus, these results can give information on the relative location of certain proteins in the 40-S subunits."} {"id": "PMID:1268252", "title": "Dual transcription of the tryptophan operon translocated into the early region of gamma.", "content": "The mode of transcription of the trp operon translocated into the early region of bacteriophage lambda was studied. Synthesis of trp mRNA specific for the translocated trp operon in lambdatrp phage was assayed after infecting a bacteria carrying a deletion mutant (trpAE1), which lacks the whole trp operon but retains a trp regulator gene (trpR). To determine trp mRNA from lambdatrp, phage phi80trp was employed as a source of DNA in hybridization assays. trp mRNA synthesis by lambdatrpE-A, which possesses the intact trp operon, was found to be only partially repressed by fully activated trp repressor in strain trpAE1. On the other hand, trp mRNA synthesis by lambdatrpE-A in strain trpAE1 (lambda), lysogenic for lambda and therefore possessing lambda repressor, was completely repressed when the trp repressor was fully activated by the addition of excess tryptophan. trp mRNA synthesis from the trp operon segment in lambdatrpBA, which carries the trpA and trpB genes but does not possess the trp promoter and operator, was not affected at all by trp repressor but was regulated completely by lambda repressor. The possibility was excluded that the trp mRNA whose synthesis is insensitive to trp repressor is anti-messenger originating from the nonsense(r)-strand of the translocated trp operon of lambdatrp. These observations led to the conclusion that transcription of the translocated trp operon in lambdatrpE-A consists of two types; one is initiated at the trp promoter and is controlled by the trp repressor, another is initiated by a lambda promoter (PL of gene N) and is controlled by the lambda repressor.", "contents": "Dual transcription of the tryptophan operon translocated into the early region of gamma. The mode of transcription of the trp operon translocated into the early region of bacteriophage lambda was studied. Synthesis of trp mRNA specific for the translocated trp operon in lambdatrp phage was assayed after infecting a bacteria carrying a deletion mutant (trpAE1), which lacks the whole trp operon but retains a trp regulator gene (trpR). To determine trp mRNA from lambdatrp, phage phi80trp was employed as a source of DNA in hybridization assays. trp mRNA synthesis by lambdatrpE-A, which possesses the intact trp operon, was found to be only partially repressed by fully activated trp repressor in strain trpAE1. On the other hand, trp mRNA synthesis by lambdatrpE-A in strain trpAE1 (lambda), lysogenic for lambda and therefore possessing lambda repressor, was completely repressed when the trp repressor was fully activated by the addition of excess tryptophan. trp mRNA synthesis from the trp operon segment in lambdatrpBA, which carries the trpA and trpB genes but does not possess the trp promoter and operator, was not affected at all by trp repressor but was regulated completely by lambda repressor. The possibility was excluded that the trp mRNA whose synthesis is insensitive to trp repressor is anti-messenger originating from the nonsense(r)-strand of the translocated trp operon of lambdatrp. These observations led to the conclusion that transcription of the translocated trp operon in lambdatrpE-A consists of two types; one is initiated at the trp promoter and is controlled by the trp repressor, another is initiated by a lambda promoter (PL of gene N) and is controlled by the lambda repressor."} {"id": "PMID:1268253", "title": "Differential sensitivity to antibiotics of trp mRNA synthesis originating at the trp promoter and the lambda promoter.", "content": "Transcription of the Escherichia coli trp operon translocated into the early region of bacteriophage lambda can occur under the control of either of two promoters, the trp promoter on the lambda promoter (OL of N gene). (Imamato, F. and Tani, S. (1972) Nat. New Biol. 240, 172-175 and Ihara S. and Imamoto, F. (1976) Biochim. Biophys. Acta 432, 199-211). Trp mRNA synthesis originating at the trp promoter stopped when translation was blocked by chloramphenicol tetracycline erythromycin or puromycin. In contrast, trp mRNA synthesis originating at the lambda promoter was not affected by antibiotic action. This probably is a reflection of the properties of the \"immediate early\" class of genes of lambda, whose transcription in initiated at the PL. promoter and is not inhibited by the antibiotic. The inference is strengthened by comparable results with phage lambdatrpE-A (carrying an intact tro operon) and lambdatrpBA (carrying the operator-distal two genes but missing the trp promoter and operator). Thus it seems that either the promoter or other gene(s) located at the beginning of the operon, either at polymerase addition or because of some feature of the transcript, can determine a requirement for \"coupling\" of RNA polymerase to the translational machinery in vivo.", "contents": "Differential sensitivity to antibiotics of trp mRNA synthesis originating at the trp promoter and the lambda promoter. Transcription of the Escherichia coli trp operon translocated into the early region of bacteriophage lambda can occur under the control of either of two promoters, the trp promoter on the lambda promoter (OL of N gene). (Imamato, F. and Tani, S. (1972) Nat. New Biol. 240, 172-175 and Ihara S. and Imamoto, F. (1976) Biochim. Biophys. Acta 432, 199-211). Trp mRNA synthesis originating at the trp promoter stopped when translation was blocked by chloramphenicol tetracycline erythromycin or puromycin. In contrast, trp mRNA synthesis originating at the lambda promoter was not affected by antibiotic action. This probably is a reflection of the properties of the \"immediate early\" class of genes of lambda, whose transcription in initiated at the PL. promoter and is not inhibited by the antibiotic. The inference is strengthened by comparable results with phage lambdatrpE-A (carrying an intact tro operon) and lambdatrpBA (carrying the operator-distal two genes but missing the trp promoter and operator). Thus it seems that either the promoter or other gene(s) located at the beginning of the operon, either at polymerase addition or because of some feature of the transcript, can determine a requirement for \"coupling\" of RNA polymerase to the translational machinery in vivo."} {"id": "PMID:1268254", "title": "Complex mitochondrial DNA in animal thyroids. A comparative study.", "content": "1. The frequency of circular dimers and catenanes was determined in thyroid mitochondrial DNA (mtDNA) from rabbits, mice, pigs, sheep and cattle. 2. The mtDNA from freshly removed thyroids was isolated by buoyant density centrifugation in ethidium bromide/CsCl gradients after DNAase treatment of the mitochondrial pellet. Typically, more than 90% of the recovered mtDNA was found in the lower band, indicating a low rate of nicking during isolation. A sample of the total mtDNA (upper and lower bands) was examined by electron microscopy after preparation by the aqueous protein film technique. 3. The frequency of circular dimers generally ranged from 0.1 to 0.3%. However, in an mtDNA sample from cow thyroid, the frequency of circular dimers was 0.6% (0.9% if circular dimers occuring in catenanes are included(, differing significantly from the frequency of these forms in bull thyroid, 0.1%. A small but significant variability also occurred in the frequency of catenanes ranging from 2 to 8% in the different groups; this variation is within the limits usually observed in normal tissues. 4. These observations indicate that thyroids, like other normal tissues examined so far, have a low content of circular dimers. A high frequency of these forms seems to be the trademark of some genetically and physiologically abnormal cells such as certain established cell lines, virus-transformed cells and malignant or otherwise pathological tissues.", "contents": "Complex mitochondrial DNA in animal thyroids. A comparative study. 1. The frequency of circular dimers and catenanes was determined in thyroid mitochondrial DNA (mtDNA) from rabbits, mice, pigs, sheep and cattle. 2. The mtDNA from freshly removed thyroids was isolated by buoyant density centrifugation in ethidium bromide/CsCl gradients after DNAase treatment of the mitochondrial pellet. Typically, more than 90% of the recovered mtDNA was found in the lower band, indicating a low rate of nicking during isolation. A sample of the total mtDNA (upper and lower bands) was examined by electron microscopy after preparation by the aqueous protein film technique. 3. The frequency of circular dimers generally ranged from 0.1 to 0.3%. However, in an mtDNA sample from cow thyroid, the frequency of circular dimers was 0.6% (0.9% if circular dimers occuring in catenanes are included(, differing significantly from the frequency of these forms in bull thyroid, 0.1%. A small but significant variability also occurred in the frequency of catenanes ranging from 2 to 8% in the different groups; this variation is within the limits usually observed in normal tissues. 4. These observations indicate that thyroids, like other normal tissues examined so far, have a low content of circular dimers. A high frequency of these forms seems to be the trademark of some genetically and physiologically abnormal cells such as certain established cell lines, virus-transformed cells and malignant or otherwise pathological tissues."} {"id": "PMID:1268255", "title": "The effect of 313 nanometer light on initiation of replicons in mammalian cell DNA containing bromodeoxyuridine.", "content": "After unifilar substitution of thymine with bromouracil in either human HeLa or bovine cells, exposure to 313 nm light inhibits initiation of clusters of replicons. Since this treatment results in damage only to DNA and because the effect is the same as observed after 100-1000 rads of X-ray irradiation to the same cells, we infer that the effect of the later treatment is also mediated almost exclusively by DNA damage.", "contents": "The effect of 313 nanometer light on initiation of replicons in mammalian cell DNA containing bromodeoxyuridine. After unifilar substitution of thymine with bromouracil in either human HeLa or bovine cells, exposure to 313 nm light inhibits initiation of clusters of replicons. Since this treatment results in damage only to DNA and because the effect is the same as observed after 100-1000 rads of X-ray irradiation to the same cells, we infer that the effect of the later treatment is also mediated almost exclusively by DNA damage."} {"id": "PMID:1268256", "title": "5-Methylcytosine in Chlorelle pyrenoidosa DNAs.", "content": "The presence of 5-methylcytosine in Chlorella pyrenoidosa (strain 211/8b) DNA's has been investigated by means of paper chromatography and thermal chromatography on hydroxyapatite. It has been shown that nuclear DNA contains 3.5 mol% 5-methylcytosine whereas no significant amount of this base can be detected in chloroplast DNA. The thermal chromatography of nuclear DNA labelled from [6-3H]- or [Me-14C] methionine lead us to conclude that the 5-methylcytosine content is directly proportional to the G + C content of the various DNA fractions. The existence of methylated sequences in DNA is postulated and the biological function of the 5-methylcytosine is discussed.", "contents": "5-Methylcytosine in Chlorelle pyrenoidosa DNAs. The presence of 5-methylcytosine in Chlorella pyrenoidosa (strain 211/8b) DNA's has been investigated by means of paper chromatography and thermal chromatography on hydroxyapatite. It has been shown that nuclear DNA contains 3.5 mol% 5-methylcytosine whereas no significant amount of this base can be detected in chloroplast DNA. The thermal chromatography of nuclear DNA labelled from [6-3H]- or [Me-14C] methionine lead us to conclude that the 5-methylcytosine content is directly proportional to the G + C content of the various DNA fractions. The existence of methylated sequences in DNA is postulated and the biological function of the 5-methylcytosine is discussed."} {"id": "PMID:1268257", "title": "Investigation of human lymphocyte plasma membrane associated nucleic acid.", "content": "Plasma membranes were prepared from the human lymphocyte cell line WIL23A by hypotonic swelling, Dounce homogenization, differential and equilibrium centrifugation. The resulting vesiculated membrane fragments were found to have densities of 1.10 and 1.17 g/ml, and were defined by lactoperoxidase mediated whole cell iodination, L-[3H] fucose incorporation, 5'-nucleotidase activity (EC 3.1.3.5) and electron micrographic visualization. Recovery of plasma membrane from whole cell homogenates was estimated to be approximately 30-35% as judged by the recovery of 125I-labeled cell surface protein. When plasma membranes were prepared from cells which had been incubated for 18 h in the presence of 0.5 muCi/ml [3H] thymidine such that greater than 10(9) acid insoluble counts could be demonstrated in the whole cell homogenates, no [3H] thymidine label and presumably, therefore, no DNA, could be shown to be coincident with either the 1.10 or 1.17 density. Similar experiments with [3H] uridine suggested that 90% of the plasma membranes did not contain RNA, while 10% remained questionable.", "contents": "Investigation of human lymphocyte plasma membrane associated nucleic acid. Plasma membranes were prepared from the human lymphocyte cell line WIL23A by hypotonic swelling, Dounce homogenization, differential and equilibrium centrifugation. The resulting vesiculated membrane fragments were found to have densities of 1.10 and 1.17 g/ml, and were defined by lactoperoxidase mediated whole cell iodination, L-[3H] fucose incorporation, 5'-nucleotidase activity (EC 3.1.3.5) and electron micrographic visualization. Recovery of plasma membrane from whole cell homogenates was estimated to be approximately 30-35% as judged by the recovery of 125I-labeled cell surface protein. When plasma membranes were prepared from cells which had been incubated for 18 h in the presence of 0.5 muCi/ml [3H] thymidine such that greater than 10(9) acid insoluble counts could be demonstrated in the whole cell homogenates, no [3H] thymidine label and presumably, therefore, no DNA, could be shown to be coincident with either the 1.10 or 1.17 density. Similar experiments with [3H] uridine suggested that 90% of the plasma membranes did not contain RNA, while 10% remained questionable."} {"id": "PMID:1268258", "title": "Evidence for the presence of mRNA in the post-ribosomal cytoplasm of sheep lymphocytes.", "content": "Several fractions of RNA prepared from the post-ribosomal cytosol of sheep lymphoid cells were found to include messenger-like RNA as defined by the following criteria: a, template activity, i.e. the ability to promote the incorporation of radioactive amino acids into protein in cell-free protein-synthesising systems derived from wheat embryos or ascites tumour cells; b, a low magnesium optimum (1-2.5 mM) for template activity which is characteristic of many natural mRNAs; c, sensitivity of the template response to aurintricarboxylic acid, a specific inhibitor of the initiation of protein synthesis. The lymphoid post-ribosomal RNA fractions, however, were translated less efficiently than were rabbit reticulocyte globin mRNA or tobacco mosaic viral (TMV) RNA; no explanation for this relatively poor template activity was found. The major fraction of messenger-like RNA had an average sedimentation coefficient of 12 S; this fraction directed the translation of several discrete polypeptides in the molecular weight range 10 000-25 000. On average the products of 12 S RNA-directed protein synthesis appeared lysine rich compared with TMV RNA-directed products. It is suggested that the apparent pool of uncommitted mRNA in resting lymphocytes may be utilised during the early stages of lymphocyte activation, and that the mRNAs could be stored in forms similar to those evident in other dormant tissues.", "contents": "Evidence for the presence of mRNA in the post-ribosomal cytoplasm of sheep lymphocytes. Several fractions of RNA prepared from the post-ribosomal cytosol of sheep lymphoid cells were found to include messenger-like RNA as defined by the following criteria: a, template activity, i.e. the ability to promote the incorporation of radioactive amino acids into protein in cell-free protein-synthesising systems derived from wheat embryos or ascites tumour cells; b, a low magnesium optimum (1-2.5 mM) for template activity which is characteristic of many natural mRNAs; c, sensitivity of the template response to aurintricarboxylic acid, a specific inhibitor of the initiation of protein synthesis. The lymphoid post-ribosomal RNA fractions, however, were translated less efficiently than were rabbit reticulocyte globin mRNA or tobacco mosaic viral (TMV) RNA; no explanation for this relatively poor template activity was found. The major fraction of messenger-like RNA had an average sedimentation coefficient of 12 S; this fraction directed the translation of several discrete polypeptides in the molecular weight range 10 000-25 000. On average the products of 12 S RNA-directed protein synthesis appeared lysine rich compared with TMV RNA-directed products. It is suggested that the apparent pool of uncommitted mRNA in resting lymphocytes may be utilised during the early stages of lymphocyte activation, and that the mRNAs could be stored in forms similar to those evident in other dormant tissues."} {"id": "PMID:1268259", "title": "Inhibitory action of different RNA fractions on the translation of globin mRNA in vitro.", "content": "Preparations of 28S rRNA and 12S RNA, obtained from sheep lymphocytes, were shown to inhibit the translation of globin mRNA. An inhibition by a given amount of 12S or 28S RNA was only obvious at saturating or near saturating levels of globin mRNA, suggesting that the inhibitory RNAs interacted with some factor essential for protein synthesis other than mRNA. The inhibitory RNAs had no effect on the translation of the synthetic template polyuridylic acid. It is suggested therefore that the target for inhibitory RNAs might be a natural mRNA specific initiation factor.", "contents": "Inhibitory action of different RNA fractions on the translation of globin mRNA in vitro. Preparations of 28S rRNA and 12S RNA, obtained from sheep lymphocytes, were shown to inhibit the translation of globin mRNA. An inhibition by a given amount of 12S or 28S RNA was only obvious at saturating or near saturating levels of globin mRNA, suggesting that the inhibitory RNAs interacted with some factor essential for protein synthesis other than mRNA. The inhibitory RNAs had no effect on the translation of the synthetic template polyuridylic acid. It is suggested therefore that the target for inhibitory RNAs might be a natural mRNA specific initiation factor."} {"id": "PMID:1268260", "title": "The electrophoretic mobility of double-stranded RNA in polyacrylamide gels as a function of molecular weight.", "content": "A re-evaluation of the mobility of double-stranded RNA on polyacrylamide gels over a molecular weight range of 0.46-6.3 . 10(6) was carried out using double-stranded RNAs of: bacteriophage \u00f86; virus like particles or mycoviruses of Penicillium chyrsogenum, Penicillium stoloniferum and Helminthosporium maydis, and reovirus type III. When the relative mobility on polyacrylamide gels was plotted as a function of log molecular weight, a smooth curve could be drawn which passed through all points. The implications of these findings to the determination of molecular weight of double-stranded RNA by polyacrylamide gel electrophoresis are discussed.", "contents": "The electrophoretic mobility of double-stranded RNA in polyacrylamide gels as a function of molecular weight. A re-evaluation of the mobility of double-stranded RNA on polyacrylamide gels over a molecular weight range of 0.46-6.3 . 10(6) was carried out using double-stranded RNAs of: bacteriophage \u00f86; virus like particles or mycoviruses of Penicillium chyrsogenum, Penicillium stoloniferum and Helminthosporium maydis, and reovirus type III. When the relative mobility on polyacrylamide gels was plotted as a function of log molecular weight, a smooth curve could be drawn which passed through all points. The implications of these findings to the determination of molecular weight of double-stranded RNA by polyacrylamide gel electrophoresis are discussed."} {"id": "PMID:1268261", "title": "Directed cleavage of ribopolynucleotides with nucleases restricted by multiple modification of substrate.", "content": "Simultaneous exhaustive modification of cytidine and uridine residues of rRNA with methoxyamine and sodium metabisulfite renders adjacent phosphodiester bonds resistant to pancreatic and T2 ribonucleases. Another method of T2 RNAase restriction is modification of cytidine with methoxyaminebisulfite followed by modification of guanosine residues with beta-ethoxy-alpha-ketobutyraldehyde. Mild alkaline treatment leads to demodification of uridine and guanosine residues leaving intact modified cytidine residues, thus providing a means of stepwise, directed cleavage of the polynucleotide. The series of combined cleavage procedures and methods of isolation of oligo(C), oligo(G) and oligopyrimidine tracts, as well as the procedure of selective cleavage at uridine residues elaborated in the course of the present studies may serve as a basis for more rational procedures of RNA sequencing.", "contents": "Directed cleavage of ribopolynucleotides with nucleases restricted by multiple modification of substrate. Simultaneous exhaustive modification of cytidine and uridine residues of rRNA with methoxyamine and sodium metabisulfite renders adjacent phosphodiester bonds resistant to pancreatic and T2 ribonucleases. Another method of T2 RNAase restriction is modification of cytidine with methoxyaminebisulfite followed by modification of guanosine residues with beta-ethoxy-alpha-ketobutyraldehyde. Mild alkaline treatment leads to demodification of uridine and guanosine residues leaving intact modified cytidine residues, thus providing a means of stepwise, directed cleavage of the polynucleotide. The series of combined cleavage procedures and methods of isolation of oligo(C), oligo(G) and oligopyrimidine tracts, as well as the procedure of selective cleavage at uridine residues elaborated in the course of the present studies may serve as a basis for more rational procedures of RNA sequencing."} {"id": "PMID:1268262", "title": "Comparisons of the low resolution structure of several small RNA-containing viruses.", "content": "A comparison is made of the structure of five small RNA-containing viruses and their accompnaying particles. The data obtained by a small-angle X-ray scattering at low resolution indicate that the radial distributions of electron density are quite similar for particles with similar percentage of RNA. Evidence is also presented indicating that the RNA probably penetrates the wall of the protein shell of most if not all of the virus particles.", "contents": "Comparisons of the low resolution structure of several small RNA-containing viruses. A comparison is made of the structure of five small RNA-containing viruses and their accompnaying particles. The data obtained by a small-angle X-ray scattering at low resolution indicate that the radial distributions of electron density are quite similar for particles with similar percentage of RNA. Evidence is also presented indicating that the RNA probably penetrates the wall of the protein shell of most if not all of the virus particles."} {"id": "PMID:1268263", "title": "[Theoretical conformational analysis of doulble-stranded polynucleotides].", "content": "Calculations of intramolecular interaction energy of two-stranded helical homopolynucleotide in the function of nine conformational variables have been carried out by the method of atom-atom potential functions. Four of these variables determine mutual position of base pairs, other four--deoxiribose ring conformation and other one--orientation of this ring with respect to the base. For this purpose an algorythm connecting dependent variables with independent ones has been developed. The investigation of energy function has shown that in the space of conformational parameters there are two valleys, which correspond to A-and B-families of conformations. Experimentaly determined conformations of two-stranded helical polynucleotides are located along the bottoms of these valleys. Along the bottom of each valley the intramolecular interaction energy changes rather little when conformational parameters change within a wide range. The valleys are separated by an energetical barrier.", "contents": "[Theoretical conformational analysis of doulble-stranded polynucleotides]. Calculations of intramolecular interaction energy of two-stranded helical homopolynucleotide in the function of nine conformational variables have been carried out by the method of atom-atom potential functions. Four of these variables determine mutual position of base pairs, other four--deoxiribose ring conformation and other one--orientation of this ring with respect to the base. For this purpose an algorythm connecting dependent variables with independent ones has been developed. The investigation of energy function has shown that in the space of conformational parameters there are two valleys, which correspond to A-and B-families of conformations. Experimentaly determined conformations of two-stranded helical polynucleotides are located along the bottoms of these valleys. Along the bottom of each valley the intramolecular interaction energy changes rather little when conformational parameters change within a wide range. The valleys are separated by an energetical barrier."} {"id": "PMID:1268264", "title": "[Dynamic theory of enzymatic catalysis].", "content": "Formal kinetics of an enzymatic reaction is considered in terms of a dynamic scheme of catalysis. Conformation reconstructions of a liberated enzyme and e-s-complex are analysed upon the phase plane. An expression for the enzyme stationary activity depending on the rate of conformation reconstructions is obtained. The case of purely dynamic catalysis is analysed and possible initiation of enzymatic activity variation in time connected with initial synchronization of molecules is shown. This phenomenon is considered as a possible criterion of the dynamic character of enzymatic catalysis.", "contents": "[Dynamic theory of enzymatic catalysis]. Formal kinetics of an enzymatic reaction is considered in terms of a dynamic scheme of catalysis. Conformation reconstructions of a liberated enzyme and e-s-complex are analysed upon the phase plane. An expression for the enzyme stationary activity depending on the rate of conformation reconstructions is obtained. The case of purely dynamic catalysis is analysed and possible initiation of enzymatic activity variation in time connected with initial synchronization of molecules is shown. This phenomenon is considered as a possible criterion of the dynamic character of enzymatic catalysis."} {"id": "PMID:1268265", "title": "[Hysteresis, multiplicity of stationary states and auto-oscillations in the reversible flow-through reaction].", "content": "A mathematical model has been investigated of a reversible flow-through reaction S1 reversible S2 catalyzed by an olygomeric enzyme E(R,T) the protomers of which undergo concerted conformational transitions R reversible T. The isosteric activation of olygomer E by product S2 binding preferably to protomer active sites in conformation R is shown to be a possible cause of hysteresis in the quasi-stationary input characteristic of the reaction, v (s2). The latter determines the rate law of the reaction, provided the concentration of S2 is a quasi-stationary one. The hysteresis of the characteristic v (s1) gives rise to multiple steady states and self-oscillations in the reaction.", "contents": "[Hysteresis, multiplicity of stationary states and auto-oscillations in the reversible flow-through reaction]. A mathematical model has been investigated of a reversible flow-through reaction S1 reversible S2 catalyzed by an olygomeric enzyme E(R,T) the protomers of which undergo concerted conformational transitions R reversible T. The isosteric activation of olygomer E by product S2 binding preferably to protomer active sites in conformation R is shown to be a possible cause of hysteresis in the quasi-stationary input characteristic of the reaction, v (s2). The latter determines the rate law of the reaction, provided the concentration of S2 is a quasi-stationary one. The hysteresis of the characteristic v (s1) gives rise to multiple steady states and self-oscillations in the reaction."} {"id": "PMID:1268266", "title": "[Autocatalysis in a stoichiometric model of energy metabolism].", "content": "A simple kinetic model of the energy metabolism with autocatalytic stoichiometric structure is analysed. The model includes the participation of ATP (a product of energy metabolism) in the activation of oxidation substrate. It is shown that the energy metabolism displays multiple steady states and autooscillations in the absense of all kinds of non-stoichiometric (allosteric, isosteric and cooperative) interactions. The results of the analysis are represented in the form of a parametric portrait. The domains of the parameter values of the oxidation substrate source are separated, which correspond to qualitatively different patterns of the model dynamic behavior. Under specified conditions the model is reduced to various versions of the Lotka model.", "contents": "[Autocatalysis in a stoichiometric model of energy metabolism]. A simple kinetic model of the energy metabolism with autocatalytic stoichiometric structure is analysed. The model includes the participation of ATP (a product of energy metabolism) in the activation of oxidation substrate. It is shown that the energy metabolism displays multiple steady states and autooscillations in the absense of all kinds of non-stoichiometric (allosteric, isosteric and cooperative) interactions. The results of the analysis are represented in the form of a parametric portrait. The domains of the parameter values of the oxidation substrate source are separated, which correspond to qualitatively different patterns of the model dynamic behavior. Under specified conditions the model is reduced to various versions of the Lotka model."} {"id": "PMID:1268267", "title": "[Kinetic regularities of RNA synthesis. VII. Accumulation of RNA precursors and the inverse problem].", "content": "Applicability limits are specified for earlier obtained solutions of particular inverse problems of accumulation kinetics of newly synthesized RNA using isotope label for immitating unstationary state in stationary cell cultures.", "contents": "[Kinetic regularities of RNA synthesis. VII. Accumulation of RNA precursors and the inverse problem]. Applicability limits are specified for earlier obtained solutions of particular inverse problems of accumulation kinetics of newly synthesized RNA using isotope label for immitating unstationary state in stationary cell cultures."} {"id": "PMID:1268268", "title": "[Spectral studies of beta-melanocyte-stimulating hormone and beta-lipotropic hormone fragment].", "content": "Secondary structure of beta-melanocyte-stimulating hormone was studied by circular dichoism and infra-red spectroscopy. Left-helical conformation of poly-L-proline II type which was stabilized by temperature reduction was found in aqueous solution; in 60% ethanole the quota of this structure sharply decreased. The investigation of hormone films at different values of relative humidity (in the course of H--D metabolism) made it possible to discover a twisted beta-form and an elongated helix of poly-L-proline II type. Temperature induced changes of circular dichroism spectra specify the peculiarities of poly-L-proline II conformation in C-end fragment of beta-lipotropic hormone.", "contents": "[Spectral studies of beta-melanocyte-stimulating hormone and beta-lipotropic hormone fragment]. Secondary structure of beta-melanocyte-stimulating hormone was studied by circular dichoism and infra-red spectroscopy. Left-helical conformation of poly-L-proline II type which was stabilized by temperature reduction was found in aqueous solution; in 60% ethanole the quota of this structure sharply decreased. The investigation of hormone films at different values of relative humidity (in the course of H--D metabolism) made it possible to discover a twisted beta-form and an elongated helix of poly-L-proline II type. Temperature induced changes of circular dichroism spectra specify the peculiarities of poly-L-proline II conformation in C-end fragment of beta-lipotropic hormone."} {"id": "PMID:1268269", "title": "[Significance of chiral purity of biomolecules for self-reproduction of organisms].", "content": "Living systems mainly syntesise and utilise chiral pure polimers which have only one form of enantiomers (l, l,..., l-proteins, d, d, d,..., d-sugars). The biologycal meaning of chiral purity of molecules in organisms is discussed. It is shown that chiral purity of biomolecules is necessary to ensure ordering of organisms during selfreproduction. Even when formation of chiral pure form does not have any advantages over formation of a set of other stereoisomers, only chiral pure molecules may act as regulators of further syntheses. Molecules with distorded chiral purity are not able to maintain the initial order during selfreproduction.", "contents": "[Significance of chiral purity of biomolecules for self-reproduction of organisms]. Living systems mainly syntesise and utilise chiral pure polimers which have only one form of enantiomers (l, l,..., l-proteins, d, d, d,..., d-sugars). The biologycal meaning of chiral purity of molecules in organisms is discussed. It is shown that chiral purity of biomolecules is necessary to ensure ordering of organisms during selfreproduction. Even when formation of chiral pure form does not have any advantages over formation of a set of other stereoisomers, only chiral pure molecules may act as regulators of further syntheses. Molecules with distorded chiral purity are not able to maintain the initial order during selfreproduction."} {"id": "PMID:1268270", "title": "[Physical model of electroexcitable membranes. II. Mechanism of excitation].", "content": "The proposed model of action potential generation in electroexcitable membranes is based on physical phenomenon of the reversible thermal dielectric breakdown induced by injection of the activating charge carriers in the membrane under irritation. The model has been shown to describe well the main features of nerve excitation.", "contents": "[Physical model of electroexcitable membranes. II. Mechanism of excitation]. The proposed model of action potential generation in electroexcitable membranes is based on physical phenomenon of the reversible thermal dielectric breakdown induced by injection of the activating charge carriers in the membrane under irritation. The model has been shown to describe well the main features of nerve excitation."} {"id": "PMID:1268271", "title": "[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. I. Statement of the problem. Stationary transfer].", "content": "The communication presented is the first in the cycle on comparative analysis of hopping (three barrier) and electrodiffusion description of particle movement in thin membranes. A case of stationary transfer is considered. It is shown that the three barrier hopping description is adequate to the electrodiffusion one when the membrane is non-uniform with a high narrow barrier in the middle. The uniform electrodiffusion description is adequate to the three barrier one only in the cases when the limiting stage is presented by the transfer through a membrane surface or the border of small outer electric fields.", "contents": "[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. I. Statement of the problem. Stationary transfer]. The communication presented is the first in the cycle on comparative analysis of hopping (three barrier) and electrodiffusion description of particle movement in thin membranes. A case of stationary transfer is considered. It is shown that the three barrier hopping description is adequate to the electrodiffusion one when the membrane is non-uniform with a high narrow barrier in the middle. The uniform electrodiffusion description is adequate to the three barrier one only in the cases when the limiting stage is presented by the transfer through a membrane surface or the border of small outer electric fields."} {"id": "PMID:1268272", "title": "[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. II. Potential clamping. Jumping and continuous uniform mechanism].", "content": "Electric relaxation of the membrane in three-barrier hopping and electrodiffusion uniform models has been considered. Both models are shown to have different relaxation characteristics which do not coiside with each other.", "contents": "[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. II. Potential clamping. Jumping and continuous uniform mechanism]. Electric relaxation of the membrane in three-barrier hopping and electrodiffusion uniform models has been considered. Both models are shown to have different relaxation characteristics which do not coiside with each other."} {"id": "PMID:1268273", "title": "[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. III. Potential clamping in a uniform membrane].", "content": "Electric relaxation of a non-uniform membrane was considered during potential clamp. It is shown that in the case of non-uniformity as a high narrow potential barrier in the middle and deep holes along the membrane edges the electrodiffusion model is adequate to the three-barrier hopping one.", "contents": "[Comparison of jumping and electrodiffusion mechanisms of particle movement in thin membranes. III. Potential clamping in a uniform membrane]. Electric relaxation of a non-uniform membrane was considered during potential clamp. It is shown that in the case of non-uniformity as a high narrow potential barrier in the middle and deep holes along the membrane edges the electrodiffusion model is adequate to the three-barrier hopping one."} {"id": "PMID:1268274", "title": "[Structure of the double electric layer at membrane/aqueous solution interfaces in the presence of tetrapentylammonium cations].", "content": "Data are presented on the conductivity of bilayer lipid membranes of phosphatidilethanole amine with different surface charges in the presence of tetrapentylammonium chloride. It follows from the analysis of experimental data that to describe the effect of surface charge on membrane conductivity it is necessary to use a complicated model of double electric layer. Only in some cases Gouy-Chapman theory well describes the experimental results.", "contents": "[Structure of the double electric layer at membrane/aqueous solution interfaces in the presence of tetrapentylammonium cations]. Data are presented on the conductivity of bilayer lipid membranes of phosphatidilethanole amine with different surface charges in the presence of tetrapentylammonium chloride. It follows from the analysis of experimental data that to describe the effect of surface charge on membrane conductivity it is necessary to use a complicated model of double electric layer. Only in some cases Gouy-Chapman theory well describes the experimental results."} {"id": "PMID:1268276", "title": "[Free radical oxidation of biological membrane lipids. VII. Effect of ultraviolet radiation on free radical oxidation of lipids complexed with protein and in biomembranes].", "content": "Promoting effect of protein component on the development of free radical oxidation in the systems ethylarahidonate--bovine serum albumin and mitochondria suspension under UV irradiation has been shown. Connection between the processes of peroxide formation and the change of the functional activity of organells has been followed.", "contents": "[Free radical oxidation of biological membrane lipids. VII. Effect of ultraviolet radiation on free radical oxidation of lipids complexed with protein and in biomembranes]. Promoting effect of protein component on the development of free radical oxidation in the systems ethylarahidonate--bovine serum albumin and mitochondria suspension under UV irradiation has been shown. Connection between the processes of peroxide formation and the change of the functional activity of organells has been followed."} {"id": "PMID:1268275", "title": "[Structural rearrangements in membranes induced by anesthetics].", "content": "Studies were carried out on the effects of anesthetics on the stability of membranes to sodium dodecylsulfate and trypsin. The initial rate of membrane desintegration by detergent evaluated by light scattering with stopped flow method was increased in the presence of ethanol, propanol, benzyl alcohol, procain-amide (erthrocyte membrane) and chlorpromazine (rat brain synaptosomes). Concentrations of anesthetics which correspond to half of the maximum effect were very close to that of blocking the action potential and inducing 50%--antihemolysis. Alcohols and procaine at anesthetic concentrations inhibited proteolysis of isolated erythrocyte membranes but were without effect on their ultrasonic fragments. Increase of membrane desintegtation rate is interpreted as structural rearrangements of membranes with the weakening of detergent sensitive intermolecular interactions. Proteolysis inhibition of ghosts but not the gragments indicates against the participation of the basic func of proteins in the structural membrane rearrangements.", "contents": "[Structural rearrangements in membranes induced by anesthetics]. Studies were carried out on the effects of anesthetics on the stability of membranes to sodium dodecylsulfate and trypsin. The initial rate of membrane desintegration by detergent evaluated by light scattering with stopped flow method was increased in the presence of ethanol, propanol, benzyl alcohol, procain-amide (erthrocyte membrane) and chlorpromazine (rat brain synaptosomes). Concentrations of anesthetics which correspond to half of the maximum effect were very close to that of blocking the action potential and inducing 50%--antihemolysis. Alcohols and procaine at anesthetic concentrations inhibited proteolysis of isolated erythrocyte membranes but were without effect on their ultrasonic fragments. Increase of membrane desintegtation rate is interpreted as structural rearrangements of membranes with the weakening of detergent sensitive intermolecular interactions. Proteolysis inhibition of ghosts but not the gragments indicates against the participation of the basic func of proteins in the structural membrane rearrangements."} {"id": "PMID:1268278", "title": "[Energy migration in photoactive complexes of chlorophyll precursor in etiolated leaves and spectroscopic characteristics of pigment forms].", "content": "Migration energy between three forms of the precursor of chlorophyll and chlorophyllide are measured and calculated. Absorption coefficients, fluorescence yields of pigment forms and dimensions of native complexes (20-22 molecules) are calculated.", "contents": "[Energy migration in photoactive complexes of chlorophyll precursor in etiolated leaves and spectroscopic characteristics of pigment forms]. Migration energy between three forms of the precursor of chlorophyll and chlorophyllide are measured and calculated. Absorption coefficients, fluorescence yields of pigment forms and dimensions of native complexes (20-22 molecules) are calculated."} {"id": "PMID:1268279", "title": "[Luminescence of bacteriorhodopsin in purple membranes from Halobacterium haolbium cells].", "content": "Red luminescence of purple membranes from Halobacterium halobium cells was found out, and its emission, excitation and polarization spectra were investigated. Simultaneous parallel measurements of absorption and luminescence changes in one sample brought about by the action of light were also carried out. The bands in the spectra can be attributed to a number of bacteriorhodpsin (BR) forms: BR(595,520), BR(650,575),BR(600-620), BR(700,625), BR(730,660) BR(780,695), where the number above is the position of the luminescence maxima, below--that of absorption. Proceding from the quantum yield of the luminescence (10(-3)) and of photoreaction (10(-1)) of BR, the photoisomerization rate constant of the latter was estimated (10(11) sec(-1). The temperature dependence of the luminescence quantum yield points to the existence of two or three quenching processes with different activation energies. BR phosphorescence was not observed in the region 500-1100 nm. High degree (36%) os luminescence polarization shows that there is no homogeneous energy transfer between BR molecules, or there is regularity in orientation of their dipoles. Energy migration from the bulk of carotenoids to BR was not found. However limited heterogeneous transfer between the different BR forms cannot be ruled out. The absence (or limitation) of migration indicated that there is a spatial separation of the chromophores. Data on possible participation of triplet states in the BR photoconversions are discussed.", "contents": "[Luminescence of bacteriorhodopsin in purple membranes from Halobacterium haolbium cells]. Red luminescence of purple membranes from Halobacterium halobium cells was found out, and its emission, excitation and polarization spectra were investigated. Simultaneous parallel measurements of absorption and luminescence changes in one sample brought about by the action of light were also carried out. The bands in the spectra can be attributed to a number of bacteriorhodpsin (BR) forms: BR(595,520), BR(650,575),BR(600-620), BR(700,625), BR(730,660) BR(780,695), where the number above is the position of the luminescence maxima, below--that of absorption. Proceding from the quantum yield of the luminescence (10(-3)) and of photoreaction (10(-1)) of BR, the photoisomerization rate constant of the latter was estimated (10(11) sec(-1). The temperature dependence of the luminescence quantum yield points to the existence of two or three quenching processes with different activation energies. BR phosphorescence was not observed in the region 500-1100 nm. High degree (36%) os luminescence polarization shows that there is no homogeneous energy transfer between BR molecules, or there is regularity in orientation of their dipoles. Energy migration from the bulk of carotenoids to BR was not found. However limited heterogeneous transfer between the different BR forms cannot be ruled out. The absence (or limitation) of migration indicated that there is a spatial separation of the chromophores. Data on possible participation of triplet states in the BR photoconversions are discussed."} {"id": "PMID:1268277", "title": "[Structural rearrangements in synaptosomal membranes of the brain].", "content": "Studies were carried out on structural state of synaptosomes and synaptic plasma membranes from brain of rats and guinea pigs at 5--50C. In membranes from guinea pig brain there were two breaks at 8 and at 18--20C in the curves of temperature dependence of light scattering. At the same temperatures adhesive properties of membranes had changed in jump-like manner when evaluating the degree of aggregation at pH4. The degree of aggregation in membranes from rat brain as well as rate of solubilization by 0.2% SDS (stoped-flow measurements) are characterized by single break point at 27C in Arrhenius curves. The breaks were interpreted as phase transitions with membrane surface involvement. Chlorpromazine and tetraciane (10(4)--10(3) M) abolished or modified these transitions. Because the number of negative charges and tryptophanyl and ANS fluorescence parameters were unchanged it was suggested that redistribution of ionogenic and hydrophobic goups took place at membrane surface during phase transitions.", "contents": "[Structural rearrangements in synaptosomal membranes of the brain]. Studies were carried out on structural state of synaptosomes and synaptic plasma membranes from brain of rats and guinea pigs at 5--50C. In membranes from guinea pig brain there were two breaks at 8 and at 18--20C in the curves of temperature dependence of light scattering. At the same temperatures adhesive properties of membranes had changed in jump-like manner when evaluating the degree of aggregation at pH4. The degree of aggregation in membranes from rat brain as well as rate of solubilization by 0.2% SDS (stoped-flow measurements) are characterized by single break point at 27C in Arrhenius curves. The breaks were interpreted as phase transitions with membrane surface involvement. Chlorpromazine and tetraciane (10(4)--10(3) M) abolished or modified these transitions. Because the number of negative charges and tryptophanyl and ANS fluorescence parameters were unchanged it was suggested that redistribution of ionogenic and hydrophobic goups took place at membrane surface during phase transitions."} {"id": "PMID:1268280", "title": "[Change in the activity of calcium ions during illumination of a suspension of visual cell outer segment fragments].", "content": "Changes in the activity of calcium ions in the medium containing outer fragments suspension of bovine eye retina rods have been studied by the method of calcium-selective electrodes. Illumination of the suspension increases calcium ion activity in the incubation medium. Photoinduced yield of calcium ions depends on Ca+2 concentration: it equals 0.11+/-0.015 M Ca2+/1m rodopsin in the medium containing 0.1 mM CaCl2 and 0.046+/-0.002Ca2+/1M rodopsin in the medium containing 0.05 mM CaCl2. In the medium containing more than 10(-4) M CaCl2 both an increase and a decrease of Ca2+ ions have been observed.", "contents": "[Change in the activity of calcium ions during illumination of a suspension of visual cell outer segment fragments]. Changes in the activity of calcium ions in the medium containing outer fragments suspension of bovine eye retina rods have been studied by the method of calcium-selective electrodes. Illumination of the suspension increases calcium ion activity in the incubation medium. Photoinduced yield of calcium ions depends on Ca+2 concentration: it equals 0.11+/-0.015 M Ca2+/1m rodopsin in the medium containing 0.1 mM CaCl2 and 0.046+/-0.002Ca2+/1M rodopsin in the medium containing 0.05 mM CaCl2. In the medium containing more than 10(-4) M CaCl2 both an increase and a decrease of Ca2+ ions have been observed."} {"id": "PMID:1268282", "title": "[Minimal mixture principle as a method of choosing the form of a dynamic model].", "content": "The extremality principle for molecular processes in biological systems is considered. The principle is based on an assumption that the main function of biological processes is the separation of the \"product\" from the \"scheme\". The form of the dynamical model of the process is determined from the requirement of the \"minimum mixture\". As an example Selkov's model of glycolysis is considered.", "contents": "[Minimal mixture principle as a method of choosing the form of a dynamic model]. The extremality principle for molecular processes in biological systems is considered. The principle is based on an assumption that the main function of biological processes is the separation of the \"product\" from the \"scheme\". The form of the dynamical model of the process is determined from the requirement of the \"minimum mixture\". As an example Selkov's model of glycolysis is considered."} {"id": "PMID:1268281", "title": "[Changes in the electrical properties of atrial trabecula induced by an electric stimulus].", "content": "Electrical activity, excitation threshold and \"steady--state\" current-voltage, relationship (estimated under voltage clamp conditions) in the membrane of chicken embryo atrial trabecula were investigated by means of double succrose-gap technique. Application of short (10 msec) electrical stimuli with magnitudes up to 6.10(-5) a (1-150 threshold) resulted in increased excitability and appearance of spontaneous activity. Release of neurotransmitters and polarity of the applied sitmulus are shown not to play a significant role in the changes in membrane excitability observed, the main cause of the latter being the increased sodium permeability of the membrane.", "contents": "[Changes in the electrical properties of atrial trabecula induced by an electric stimulus]. Electrical activity, excitation threshold and \"steady--state\" current-voltage, relationship (estimated under voltage clamp conditions) in the membrane of chicken embryo atrial trabecula were investigated by means of double succrose-gap technique. Application of short (10 msec) electrical stimuli with magnitudes up to 6.10(-5) a (1-150 threshold) resulted in increased excitability and appearance of spontaneous activity. Release of neurotransmitters and polarity of the applied sitmulus are shown not to play a significant role in the changes in membrane excitability observed, the main cause of the latter being the increased sodium permeability of the membrane."} {"id": "PMID:1268284", "title": "[Theory of EEG potentials in a model of thin brain integuments. II. Model of a multilayer flat cable].", "content": "A model of a polylayer spheric cable for estimating EEG potentials was discussed earlier [1]. As far as the holes in the natural scull were ignored in that model, the contrary assumption is useful: the scull is regarded as an infinite plain. Among the solution of the equations of both models there exist uncomplicated relations.", "contents": "[Theory of EEG potentials in a model of thin brain integuments. II. Model of a multilayer flat cable]. A model of a polylayer spheric cable for estimating EEG potentials was discussed earlier [1]. As far as the holes in the natural scull were ignored in that model, the contrary assumption is useful: the scull is regarded as an infinite plain. Among the solution of the equations of both models there exist uncomplicated relations."} {"id": "PMID:1268285", "title": "[Effect of delay on auto-oscillations in cell populations].", "content": "A model of homogenous cell population is analysed, the mitotic activity of which is controled by an inhibitor produced by the cells themselves. While deducing the model it is assumed that the inhibitor concentration is proportional to the population density at some preceding time moment. The density change in time is described by a delay differential equation: dx/dt=alpha x/(1+x(v)(t--0))--x. According to this equation oscillation of cell number may be observed in the population with an increase of the critical value of delay in the mechanism of mitotic activity inhibition. The oscillation period determined analytically in linear approximation equals the quadruplicated time of delay. Numerical integration of the model has shown that the period observed is close to the calculated one.", "contents": "[Effect of delay on auto-oscillations in cell populations]. A model of homogenous cell population is analysed, the mitotic activity of which is controled by an inhibitor produced by the cells themselves. While deducing the model it is assumed that the inhibitor concentration is proportional to the population density at some preceding time moment. The density change in time is described by a delay differential equation: dx/dt=alpha x/(1+x(v)(t--0))--x. According to this equation oscillation of cell number may be observed in the population with an increase of the critical value of delay in the mechanism of mitotic activity inhibition. The oscillation period determined analytically in linear approximation equals the quadruplicated time of delay. Numerical integration of the model has shown that the period observed is close to the calculated one."} {"id": "PMID:1268283", "title": "[Role of entering currents in the accommodation of myocardial fibers].", "content": "Varying ionic composition of outher medium and applying specific agents the role of fast and slow systems of entering currents in the accommodation of cats ventricular fibres has been studied. In potential region close to the level of resting potential (membrane depolarization no larger than 20-30mv), accomodation mainly depends on fast sodium currents. It is inhibited with a rise of this current (akonitin 0.1--1 mg) and, on the contrary, it increases when it gets weaker (novacain 2--5 mM). In the region of more positive potentials (membrane depolarization more than by 30 mv) the accommodation is mainly determined by the slow NA--Ca-systems of channels. The agents which strengthen NA--Ca--current (Si2+--5mM, Ca2+--10mM, Ba2+--0.1 mM) reduce the accommodation in the activation region of the Na--Ca--system. The agents which weaken the slow current (Mn2+--3 mM, isoptin--2+5 mg/l, inderal--2 mg/l) produce an opposite effect.", "contents": "[Role of entering currents in the accommodation of myocardial fibers]. Varying ionic composition of outher medium and applying specific agents the role of fast and slow systems of entering currents in the accommodation of cats ventricular fibres has been studied. In potential region close to the level of resting potential (membrane depolarization no larger than 20-30mv), accomodation mainly depends on fast sodium currents. It is inhibited with a rise of this current (akonitin 0.1--1 mg) and, on the contrary, it increases when it gets weaker (novacain 2--5 mM). In the region of more positive potentials (membrane depolarization more than by 30 mv) the accommodation is mainly determined by the slow NA--Ca-systems of channels. The agents which strengthen NA--Ca--current (Si2+--5mM, Ca2+--10mM, Ba2+--0.1 mM) reduce the accommodation in the activation region of the Na--Ca--system. The agents which weaken the slow current (Mn2+--3 mM, isoptin--2+5 mg/l, inderal--2 mg/l) produce an opposite effect."} {"id": "PMID:1268286", "title": "[Dynamics of O2 and CO2 tensions in the brain (mathematical modeling)].", "content": "The mathematical model for description of the circulation and gas exchange dynamics in the brain is suggested. The model is based on a cell of two compact parallel capillary network with a brain tissue within. The equation system describing the model was calculated on a computer. The simulation showed that steady state pO2 in the cell during blood flow changes from 0.5 mm/sec to 0.25 or 1 mm/sec is reached within 2--5 sec. The dynamics of pCO2 is more inert. It was shown that the main factor in the dynamics of pO2 in the brain is the velocity of blood flow in capillaries. The dynamic pattern of pCO2 depends on haemodynamical condition, the structure of capillary network and physical properties of CO2.", "contents": "[Dynamics of O2 and CO2 tensions in the brain (mathematical modeling)]. The mathematical model for description of the circulation and gas exchange dynamics in the brain is suggested. The model is based on a cell of two compact parallel capillary network with a brain tissue within. The equation system describing the model was calculated on a computer. The simulation showed that steady state pO2 in the cell during blood flow changes from 0.5 mm/sec to 0.25 or 1 mm/sec is reached within 2--5 sec. The dynamics of pCO2 is more inert. It was shown that the main factor in the dynamics of pO2 in the brain is the velocity of blood flow in capillaries. The dynamic pattern of pCO2 depends on haemodynamical condition, the structure of capillary network and physical properties of CO2."} {"id": "PMID:1268288", "title": "[Identification of neuronal system objects with standards].", "content": "At some fixed position of a three-dimensional object in relation to the retina plane let us name the set of coordinates of its characteristical points the standard. It is shown that the projections of the objects to the retinamay be identified with their standard (independent of the objects shift, their rotation, change of the scale and of partial shielding of some objects by the other). The structure of the net system is presented which consists of linear, threshold and integrating neurons where such identification may be performed. The system consists of a net with a feedback for calculating optimal transformations, a net for calculating the degree of proximity between the reflection and the standard and a net generator of hypotheses on the correspondence of characteristical points. All the objects whose standards are presented in the system may be identified simultaneously.", "contents": "[Identification of neuronal system objects with standards]. At some fixed position of a three-dimensional object in relation to the retina plane let us name the set of coordinates of its characteristical points the standard. It is shown that the projections of the objects to the retinamay be identified with their standard (independent of the objects shift, their rotation, change of the scale and of partial shielding of some objects by the other). The structure of the net system is presented which consists of linear, threshold and integrating neurons where such identification may be performed. The system consists of a net with a feedback for calculating optimal transformations, a net for calculating the degree of proximity between the reflection and the standard and a net generator of hypotheses on the correspondence of characteristical points. All the objects whose standards are presented in the system may be identified simultaneously."} {"id": "PMID:1268289", "title": "[Phenomenological model of the system for exact determination of target direction by the bat echolator].", "content": "A functional scheme of correlation treatment of an echosignal during the determination of a direction to the target by rats echolator is considered. The scheme proceeds from a suggestion that for an exact measurement of angle coordinates of the target the rat applies a location method of unisignal zones resulting from the pulsation of direction diagram when LFM impulse is emitted. Some considerations in favour of the suggested phenomenological model are presented. An experimental set-up which permits to test and specify the model is proposed.", "contents": "[Phenomenological model of the system for exact determination of target direction by the bat echolator]. A functional scheme of correlation treatment of an echosignal during the determination of a direction to the target by rats echolator is considered. The scheme proceeds from a suggestion that for an exact measurement of angle coordinates of the target the rat applies a location method of unisignal zones resulting from the pulsation of direction diagram when LFM impulse is emitted. Some considerations in favour of the suggested phenomenological model are presented. An experimental set-up which permits to test and specify the model is proposed."} {"id": "PMID:1268290", "title": "[Further study of the model of a human skull as a cupola with a plane base].", "content": "An experimental study of the base deformation of isolated human scull under conditions of scull collision with an obstacle has been carried out. The findings are compared with human cerebrospinal traums phenomena. An earlier suggested continuous scull model is modified on the basis of the data obtained. It is shown that the modified model (a part of spherical shell with the flat base) resembles scull behaviour in statics and dynamics better than the scull model in the form of spherical shell.", "contents": "[Further study of the model of a human skull as a cupola with a plane base]. An experimental study of the base deformation of isolated human scull under conditions of scull collision with an obstacle has been carried out. The findings are compared with human cerebrospinal traums phenomena. An earlier suggested continuous scull model is modified on the basis of the data obtained. It is shown that the modified model (a part of spherical shell with the flat base) resembles scull behaviour in statics and dynamics better than the scull model in the form of spherical shell."} {"id": "PMID:1268306", "title": "Biochemical and ultrastructural study of human diabetic conjunctiva.", "content": "Combined biochemical and ultrastructural study of conjunctival biopsies of 27 normal subjects and 45 diabetics (40 to 60 years old) was made. The \"in vitro\" incorporation of 14C-glucosamine and 3H-proline in freshly excised conjunctival biopsies was studied. The alterations of the capillary basement membrane of the conjunctiva were studied by electron microscopy. The following results were obtained: 1) A decrease of the specific activity of 14C-glucosmaine incorporation was found in fractions of diabetic conjunctiva. 2) In diabetic conjunctiva the percentages of 3H-proline incorporation in polymeric collagen containing fraction and structural glycoproteins containing fraction were significantly increased with a parallel decrease of 3H-proline incorporation in \"crude soluble collagen\" fraction expressed as a percentage of total incorporation. 3) Significant thickening of capillary basement membrane was observed with the appearance of collagen-like fibrils within the basement membrane in diabetic conjunctiva. Such fibrils were not seen in normal basement membranes. A relation between the extent of basement membrane thickening and the appearance of collagen-like fibrils is suggested. 4) The higher percentage of incorporation of 3H-proline in polymeric collagen may be related to the appearance of collagen fibrils in thickened basement membranes of the diabetic conjunctival capillaries. 5) These results suggest an abnormal regulation of the relative rate of biosynthesis and/or excretion of intercellular matrix macromolecules (collagen, structural glycoproteins) as part of the metabolic disorders characterising diabetes.", "contents": "Biochemical and ultrastructural study of human diabetic conjunctiva. Combined biochemical and ultrastructural study of conjunctival biopsies of 27 normal subjects and 45 diabetics (40 to 60 years old) was made. The \"in vitro\" incorporation of 14C-glucosamine and 3H-proline in freshly excised conjunctival biopsies was studied. The alterations of the capillary basement membrane of the conjunctiva were studied by electron microscopy. The following results were obtained: 1) A decrease of the specific activity of 14C-glucosmaine incorporation was found in fractions of diabetic conjunctiva. 2) In diabetic conjunctiva the percentages of 3H-proline incorporation in polymeric collagen containing fraction and structural glycoproteins containing fraction were significantly increased with a parallel decrease of 3H-proline incorporation in \"crude soluble collagen\" fraction expressed as a percentage of total incorporation. 3) Significant thickening of capillary basement membrane was observed with the appearance of collagen-like fibrils within the basement membrane in diabetic conjunctiva. Such fibrils were not seen in normal basement membranes. A relation between the extent of basement membrane thickening and the appearance of collagen-like fibrils is suggested. 4) The higher percentage of incorporation of 3H-proline in polymeric collagen may be related to the appearance of collagen fibrils in thickened basement membranes of the diabetic conjunctival capillaries. 5) These results suggest an abnormal regulation of the relative rate of biosynthesis and/or excretion of intercellular matrix macromolecules (collagen, structural glycoproteins) as part of the metabolic disorders characterising diabetes."} {"id": "PMID:1268310", "title": "[Effects of arginine and growth hormone, administered in vivo and in vitro, on the oxygen consumption of rat liver hemogenates].", "content": "Effects of arginine aspartate, arginine chlorhydrate, potassium aspartate, with equal arginine base and aspartate ion available for all there compounds, growth hormone, and association of these different substances, are studied on rat hepatic homogenates oxygen consumption during 7 to 12 h, after injection to rats 1 h before sacrifice (A.A.: 0.50 g, C.A.: 0.34 g, A.K.: 0.22 g, STH: 2 U.I.), or \"in vitro\" adjunction to the preparation (A.A.: 0.125 g, C.A.: 0.085 g. A.K.: 0.055 g. STH: 0.5 U.I./0.25 g of liver). 1) \"In vivo\", arginine (endogenous STH secretion stimulation) is active: A.A. (+23% to +96% from 1 h to 8 h, p is less than 0.01), C.A. (+49% from 5 h to 8 h, p is less than 0.01), whereas potassium aspartate is inactive. \"In vitro\", aspartate is active: A.K. (+24% to +147% from 4 h to 12 h, (p is less than 0.01), A.A. (+56% to +53% from 7 h to 12 h, p is less than 0.01), whereas arginine without aspartate: C.A. is inactive. 2) Exogenous STH is active \"in vivo\" (+111% from 5 h to 8 h, p is less than 0.01) and \"in vitro\" (+31% from 4 h to 7 h, p is less than 0.01). 3) Association A.A. + STH (endogenous STH + exogenous STH) when given \"in vivo\", dose not produce any additive effect the tissue Vo2 release (+91% from 5 h to 8 h, p is less than 0.01) does not differ from STH and A.A. Aspartate added to STH \"in vitro\" enhances STH effects: (A.A. + STH: + 44% to +114% from 4 h to 12 h, p is less than 0.01, A.K. + STH: 73% to + 152% from 4 h to 12 h, p is less than 0.01).", "contents": "[Effects of arginine and growth hormone, administered in vivo and in vitro, on the oxygen consumption of rat liver hemogenates]. Effects of arginine aspartate, arginine chlorhydrate, potassium aspartate, with equal arginine base and aspartate ion available for all there compounds, growth hormone, and association of these different substances, are studied on rat hepatic homogenates oxygen consumption during 7 to 12 h, after injection to rats 1 h before sacrifice (A.A.: 0.50 g, C.A.: 0.34 g, A.K.: 0.22 g, STH: 2 U.I.), or \"in vitro\" adjunction to the preparation (A.A.: 0.125 g, C.A.: 0.085 g. A.K.: 0.055 g. STH: 0.5 U.I./0.25 g of liver). 1) \"In vivo\", arginine (endogenous STH secretion stimulation) is active: A.A. (+23% to +96% from 1 h to 8 h, p is less than 0.01), C.A. (+49% from 5 h to 8 h, p is less than 0.01), whereas potassium aspartate is inactive. \"In vitro\", aspartate is active: A.K. (+24% to +147% from 4 h to 12 h, (p is less than 0.01), A.A. (+56% to +53% from 7 h to 12 h, p is less than 0.01), whereas arginine without aspartate: C.A. is inactive. 2) Exogenous STH is active \"in vivo\" (+111% from 5 h to 8 h, p is less than 0.01) and \"in vitro\" (+31% from 4 h to 7 h, p is less than 0.01). 3) Association A.A. + STH (endogenous STH + exogenous STH) when given \"in vivo\", dose not produce any additive effect the tissue Vo2 release (+91% from 5 h to 8 h, p is less than 0.01) does not differ from STH and A.A. Aspartate added to STH \"in vitro\" enhances STH effects: (A.A. + STH: + 44% to +114% from 4 h to 12 h, p is less than 0.01, A.K. + STH: 73% to + 152% from 4 h to 12 h, p is less than 0.01)."} {"id": "PMID:1268311", "title": "[Effects of colchicine, vinblastine and mercury p-hydroxybenzoate on the multiplication of adenovirus 5 in HeLa cells].", "content": "After 30 min incubation at 37 with 10(-4) M PHMB (p-hydroxymercuribenzoate), monolayers of HeLa cells are not affected; after 3 h exposure to 10(-5) M colchicin or 2.5 X 10(-5) M vinblastine, HeLa cells are not altered morphologically but the number of cells is decreasing between 1 and 2 days post treatment. When cells are kept in suspension after trypsinization, their ability to adhere to the Petri dishes is not altered with 10(-4) M PHMB but only 50% of the cells are able to attach after treatment with colchicine or vinblastine. Adenovirus type 5 is unsensitive to the effect of colchicine and vinblastine at various concentrations, after 3 h incubation at 37. With 10(-3) M PHMB, the virus is inactivated, infectivity and hemagglutinating activity are almost abolished but the particles are unsensitive to pancreatic DNase, so that the structure of the viral particle is intact. This effect is reduced with 10(-4) M PHMB. The adenovirus 5 multiplication is not affected when HeLa cells are treated with 10(-5) M colchicine or 2.5 X 10(-5) M vinblastine, before and during adsorption of the virus. The viral production decreases after 24 h treatment with colchicine or vinblastine. Treatment with 10(-4) M PHMB does not influence intra- or extracellular viral yield.", "contents": "[Effects of colchicine, vinblastine and mercury p-hydroxybenzoate on the multiplication of adenovirus 5 in HeLa cells]. After 30 min incubation at 37 with 10(-4) M PHMB (p-hydroxymercuribenzoate), monolayers of HeLa cells are not affected; after 3 h exposure to 10(-5) M colchicin or 2.5 X 10(-5) M vinblastine, HeLa cells are not altered morphologically but the number of cells is decreasing between 1 and 2 days post treatment. When cells are kept in suspension after trypsinization, their ability to adhere to the Petri dishes is not altered with 10(-4) M PHMB but only 50% of the cells are able to attach after treatment with colchicine or vinblastine. Adenovirus type 5 is unsensitive to the effect of colchicine and vinblastine at various concentrations, after 3 h incubation at 37. With 10(-3) M PHMB, the virus is inactivated, infectivity and hemagglutinating activity are almost abolished but the particles are unsensitive to pancreatic DNase, so that the structure of the viral particle is intact. This effect is reduced with 10(-4) M PHMB. The adenovirus 5 multiplication is not affected when HeLa cells are treated with 10(-5) M colchicine or 2.5 X 10(-5) M vinblastine, before and during adsorption of the virus. The viral production decreases after 24 h treatment with colchicine or vinblastine. Treatment with 10(-4) M PHMB does not influence intra- or extracellular viral yield."} {"id": "PMID:1268321", "title": "Qualitative and quantitative mass spectrometry of some biologically important trace metals as their tetraphenylporphyrin chelates.", "content": "The use of the mass spectrometric integrated ion current technique for the quantitative analysis of some trace metals at their tetraphenylporphyrin chelates is described. The linearity of the calibration curves and the sensitivity of the technique are improved by employing deuterated tetraphenylporphyrin chelates as loading agents. Femtomole quantities of the chelates may be detected. The use of deuterated tetraphynylporphyrin chelates as internal standards overcomes the problems of losses occurring during chromatographic separation and by thermal decomposition in the mass spectrometer.", "contents": "Qualitative and quantitative mass spectrometry of some biologically important trace metals as their tetraphenylporphyrin chelates. The use of the mass spectrometric integrated ion current technique for the quantitative analysis of some trace metals at their tetraphenylporphyrin chelates is described. The linearity of the calibration curves and the sensitivity of the technique are improved by employing deuterated tetraphenylporphyrin chelates as loading agents. Femtomole quantities of the chelates may be detected. The use of deuterated tetraphynylporphyrin chelates as internal standards overcomes the problems of losses occurring during chromatographic separation and by thermal decomposition in the mass spectrometer."} {"id": "PMID:1268322", "title": "Gas chromatographic mass spectrometric evaluation of free organic acids in human saliva.", "content": "Excellent resolution and subsequent identification of free organic acids extracted from mixed, unstimulated human saliva was obtained by gas chromatography using high resolution open tubular glass capillary columns coupled with mass spectrometry computer instrumentation. In addition to the organic acids, identified as their trimethylsilyl derivaties, the presence of 2,6-di-t-butylcresol--a food preservative--and cholesterol was established by mass spectrometry. The effects of aspirin ingestion as well as diurnal variation were studied to demonstrate the possible clinical significance of this noninvasive approach to metabolic profiling.", "contents": "Gas chromatographic mass spectrometric evaluation of free organic acids in human saliva. Excellent resolution and subsequent identification of free organic acids extracted from mixed, unstimulated human saliva was obtained by gas chromatography using high resolution open tubular glass capillary columns coupled with mass spectrometry computer instrumentation. In addition to the organic acids, identified as their trimethylsilyl derivaties, the presence of 2,6-di-t-butylcresol--a food preservative--and cholesterol was established by mass spectrometry. The effects of aspirin ingestion as well as diurnal variation were studied to demonstrate the possible clinical significance of this noninvasive approach to metabolic profiling."} {"id": "PMID:1268323", "title": "Mass spectra of delta 4- and 5 alpha-3-ketosteroids formed during the oxidation of some 3 beta-hydroxysteroids by cholesterol oxidase.", "content": "Thirty-six delta5- and 5'alpha-3beta-hydroxysteroids have been oxidized with cholesterol oxidase to give the corresponding delta4- and 5alpha-3-ketosteroids, respectively. The mass spectral characteristics of the products (or their trimethylsilyl ether derivatives, in the case of 3-keto-hydroxysteroids) varied considerably, depending especially on the nature of the C-17 sidechain. The ion of m/e 124 (or its equivalent) from cleavage of ring B was frequently a major fragment from delta4-3-ketosteroids, but in some instances was of insignificant abundance. Trimethylsilylation of the product of the oxidation of neoergosterol gave neoergosterone enol-trimethylsilyl ether. Fragmentations of the sidechain predominated in the mass spectra of the 5alpha-3-ketosteroids.", "contents": "Mass spectra of delta 4- and 5 alpha-3-ketosteroids formed during the oxidation of some 3 beta-hydroxysteroids by cholesterol oxidase. Thirty-six delta5- and 5'alpha-3beta-hydroxysteroids have been oxidized with cholesterol oxidase to give the corresponding delta4- and 5alpha-3-ketosteroids, respectively. The mass spectral characteristics of the products (or their trimethylsilyl ether derivatives, in the case of 3-keto-hydroxysteroids) varied considerably, depending especially on the nature of the C-17 sidechain. The ion of m/e 124 (or its equivalent) from cleavage of ring B was frequently a major fragment from delta4-3-ketosteroids, but in some instances was of insignificant abundance. Trimethylsilylation of the product of the oxidation of neoergosterol gave neoergosterone enol-trimethylsilyl ether. Fragmentations of the sidechain predominated in the mass spectra of the 5alpha-3-ketosteroids."} {"id": "PMID:1268324", "title": "Adsorption of tryptophan metabolites from physiological fluids on XAD-2 and determination by single ion monitoring.", "content": "Endogenous tryptamine, 5-hydroxytryptamine, indoleacetic acid, 5-hydroxyindoleacetic and tryptophan have been recovered from urine and cerebro-spinal fluid by adsorption on XAD-2 resin (0.3 g). After adsorption of the sample on the resin, desorption with methanol provides a single fraction that contains all of these metabolites. The mass spectra of their pentafluoropropionyl derivatives show prominent ions at m/e 276 and 438 which are characteristic of indoles and 5-hydroxyindoles, respectively, a feature that allows the concurrent determination of all the components of each group by functional group analysis. A method has been developed to carry out single ion monitoring with the peak matching system of an Hitachi RMU-6H mass spectrometer. Identifications are based on the respective Kovats Indices and single ion monitoring of two characteristic ions per compound: tryptophan (m/e 276 and 347); tryptamine (m/e 276 and 289); indoleacetic acid (m/e 276 and 335); 5-hydroxytryptamine (m/e 438 and 451); 5-hydroxyindoleacetic acid (m/e 438 and 497). The method described illustrates the feasibility of assaying biogenic indoleamines and acidic metabolites, as well as their precursor amino acid on a single fraction in contrast to other standard fractionation methods. This is possible even if the mass spectrometer is not equipped with an alternating voltage accelerator provided that it has a peak matcher, although the lack of an alternating voltage accelerator requires two separate injections of the same sample, for quantification and identification; one for the indole profile and another for the 5-hydroxyindole profile. Both profiles can be verified by individual monitoring of the other confirmatory ions. With this method the use of a multiple ion detector would allow a simultaneous determination of all of these metabolites in one gas chromatograph mass spectrometer run.", "contents": "Adsorption of tryptophan metabolites from physiological fluids on XAD-2 and determination by single ion monitoring. Endogenous tryptamine, 5-hydroxytryptamine, indoleacetic acid, 5-hydroxyindoleacetic and tryptophan have been recovered from urine and cerebro-spinal fluid by adsorption on XAD-2 resin (0.3 g). After adsorption of the sample on the resin, desorption with methanol provides a single fraction that contains all of these metabolites. The mass spectra of their pentafluoropropionyl derivatives show prominent ions at m/e 276 and 438 which are characteristic of indoles and 5-hydroxyindoles, respectively, a feature that allows the concurrent determination of all the components of each group by functional group analysis. A method has been developed to carry out single ion monitoring with the peak matching system of an Hitachi RMU-6H mass spectrometer. Identifications are based on the respective Kovats Indices and single ion monitoring of two characteristic ions per compound: tryptophan (m/e 276 and 347); tryptamine (m/e 276 and 289); indoleacetic acid (m/e 276 and 335); 5-hydroxytryptamine (m/e 438 and 451); 5-hydroxyindoleacetic acid (m/e 438 and 497). The method described illustrates the feasibility of assaying biogenic indoleamines and acidic metabolites, as well as their precursor amino acid on a single fraction in contrast to other standard fractionation methods. This is possible even if the mass spectrometer is not equipped with an alternating voltage accelerator provided that it has a peak matcher, although the lack of an alternating voltage accelerator requires two separate injections of the same sample, for quantification and identification; one for the indole profile and another for the 5-hydroxyindole profile. Both profiles can be verified by individual monitoring of the other confirmatory ions. With this method the use of a multiple ion detector would allow a simultaneous determination of all of these metabolites in one gas chromatograph mass spectrometer run."} {"id": "PMID:1268325", "title": "Autoclavable low cost serum-free cell culture media: the growth of established cell lines and production of viruses.", "content": "Five cell lines (BSC-1, CHO, Balb/c 3T3, HeLa, and KB) have been grown in serum-free media for several months with regular schedules of media changing and subculturing. The medium found to be successful in all cases was MEM-alpha (without the ribosides and deoxyribosides) supplemented with 1% bacteropeptone, although simple MEM (minimum essental medium (Eagle) with bacteropeptone (BP) gave fairly good growth in the case of BSC-1 and 3T3 cells. The addition of insulin was necessary for CHO, 3T3, HeLa, and KB cells. Only the BSC-1 cells grew exclusively as a stationary suspensions and the 3T3 cells growing as a combination of monalayer and suspension depending on the age of the culture and the nature of the growth surface. SV40 was produced in BSC-1 cells grown and infected in the MEM-alpha, bactopeptone medium and adenovirus-2 was produced in spinners of HeLa and KB cells grown in MEM-alpha, bactopeptone, PVP-360, and insulin. The yield of virus and infectivity of the viruses produced were about the same as those produced in conventional serum-containing systems.", "contents": "Autoclavable low cost serum-free cell culture media: the growth of established cell lines and production of viruses. Five cell lines (BSC-1, CHO, Balb/c 3T3, HeLa, and KB) have been grown in serum-free media for several months with regular schedules of media changing and subculturing. The medium found to be successful in all cases was MEM-alpha (without the ribosides and deoxyribosides) supplemented with 1% bacteropeptone, although simple MEM (minimum essental medium (Eagle) with bacteropeptone (BP) gave fairly good growth in the case of BSC-1 and 3T3 cells. The addition of insulin was necessary for CHO, 3T3, HeLa, and KB cells. Only the BSC-1 cells grew exclusively as a stationary suspensions and the 3T3 cells growing as a combination of monalayer and suspension depending on the age of the culture and the nature of the growth surface. SV40 was produced in BSC-1 cells grown and infected in the MEM-alpha, bactopeptone medium and adenovirus-2 was produced in spinners of HeLa and KB cells grown in MEM-alpha, bactopeptone, PVP-360, and insulin. The yield of virus and infectivity of the viruses produced were about the same as those produced in conventional serum-containing systems."} {"id": "PMID:1268327", "title": "Kinetic analysis of penicillin production by semicontinuous fermenters.", "content": "The relationships between the specific rate of nutrient consumption and biomass growth and between the specific rate of penicillin production and oxygen concentration in the broth are analyzed. The functional dependencies which have been obtained from the experimental data of industrial fermenters are used with the mass balances to develop a model of the behavior of semicontinous operations. The proposed model allows one to study the influence of some operational parameters. The obtained results agree with the data of industrial processes.", "contents": "Kinetic analysis of penicillin production by semicontinuous fermenters. The relationships between the specific rate of nutrient consumption and biomass growth and between the specific rate of penicillin production and oxygen concentration in the broth are analyzed. The functional dependencies which have been obtained from the experimental data of industrial fermenters are used with the mass balances to develop a model of the behavior of semicontinous operations. The proposed model allows one to study the influence of some operational parameters. The obtained results agree with the data of industrial processes."} {"id": "PMID:1268328", "title": "The influence of oxygen concentration and of specific rate of growth on the kinetics of penicillin production.", "content": "The role of fundamental parameters in the conduction of penicillin semicontinuous fermentations is analyzed. Biomass concentration, penicillin production, and main nutrient consumption are particularly studied. Furthermore, the conduction of the operation is simulated with regard to conditions of constant specific rate of growth and of constant oxygen concentration in the broth. An intermediate condition is also considered.", "contents": "The influence of oxygen concentration and of specific rate of growth on the kinetics of penicillin production. The role of fundamental parameters in the conduction of penicillin semicontinuous fermentations is analyzed. Biomass concentration, penicillin production, and main nutrient consumption are particularly studied. Furthermore, the conduction of the operation is simulated with regard to conditions of constant specific rate of growth and of constant oxygen concentration in the broth. An intermediate condition is also considered."} {"id": "PMID:1268333", "title": "Time delay in simple chemostat models.", "content": "The models of Monod and Williams, for the growth of unicellular organisms in chemostats, give strongly damped transients in the biomass and cell number when the flow rate of the chemostat is changed. A simple trick is used to incorporate time delay in these models while still allowing a conventional stability analysis. For long enough time delays the equilibrium point is unstable and limit cycles can be compared. Results obtained using Williams' model, with weakly damped transients as a result of using moderately long time delay, are compared with his data in which cell numbers show weak damping but biomass shows strong damping.", "contents": "Time delay in simple chemostat models. The models of Monod and Williams, for the growth of unicellular organisms in chemostats, give strongly damped transients in the biomass and cell number when the flow rate of the chemostat is changed. A simple trick is used to incorporate time delay in these models while still allowing a conventional stability analysis. For long enough time delays the equilibrium point is unstable and limit cycles can be compared. Results obtained using Williams' model, with weakly damped transients as a result of using moderately long time delay, are compared with his data in which cell numbers show weak damping but biomass shows strong damping."} {"id": "PMID:1268334", "title": "Electromagnetic induced kinetic effects on charged substrates in localized enzyme systems.", "content": "An analytical expression for the rate efficiency factor of planar localized enzyme systems is derived. The derivation takes into account the isothermal kinetic effect under the externally imposed perturbation of combined electrostatic and high frequency time-varying fields. The contribution of each individual field to the enzyme reaction is examined through the basic mechanism in which charged substrates interact with the specific perturbing field. The interaction mechanisms for the electrostatic and for the time-varying fields are found to be different. This difference regulates the different manners in which enzymatic reaction rates are altered. Enzymatic reactions under electrostatic perturbation can be retarded or enhanced depending on the field polarization. At sufficiently high field intensities the reaction rate may approach zero or approach a maximum value equal to the turnover number of the enzyme. Time-varying field perturbations, on the other hand, always enhance the enzymatic reactions if bunching effects are negligible. At sufficiently high field intensities, the reaction may approach a value equal to that of the free enzyme system. Several typical numerical examples on pure eletrostatic field perturbations, pure time-varying field perturbations, and combined field perturbations are also presented.", "contents": "Electromagnetic induced kinetic effects on charged substrates in localized enzyme systems. An analytical expression for the rate efficiency factor of planar localized enzyme systems is derived. The derivation takes into account the isothermal kinetic effect under the externally imposed perturbation of combined electrostatic and high frequency time-varying fields. The contribution of each individual field to the enzyme reaction is examined through the basic mechanism in which charged substrates interact with the specific perturbing field. The interaction mechanisms for the electrostatic and for the time-varying fields are found to be different. This difference regulates the different manners in which enzymatic reaction rates are altered. Enzymatic reactions under electrostatic perturbation can be retarded or enhanced depending on the field polarization. At sufficiently high field intensities the reaction rate may approach zero or approach a maximum value equal to the turnover number of the enzyme. Time-varying field perturbations, on the other hand, always enhance the enzymatic reactions if bunching effects are negligible. At sufficiently high field intensities, the reaction may approach a value equal to that of the free enzyme system. Several typical numerical examples on pure eletrostatic field perturbations, pure time-varying field perturbations, and combined field perturbations are also presented."} {"id": "PMID:1268335", "title": "[3 cases of eosinophilic leukemia with atypical granulation in the eosinophils and neutrophils].", "content": "Three patients with eosinophilic leukemia and atypical granulation in the eosinophils are described. A remarkable light and electron microscopic finding was the appearance of enormous granules in the neurtophils and eosinophils. In addition the usual anomalies seen in acute leukemia, for example asynchronisation in cell maturation, fibrillar bundles, shrinkage of nucleolus and cell organelles, signs of degeneration and also the auer-rods characteristic of AML are observed.", "contents": "[3 cases of eosinophilic leukemia with atypical granulation in the eosinophils and neutrophils]. Three patients with eosinophilic leukemia and atypical granulation in the eosinophils are described. A remarkable light and electron microscopic finding was the appearance of enormous granules in the neurtophils and eosinophils. In addition the usual anomalies seen in acute leukemia, for example asynchronisation in cell maturation, fibrillar bundles, shrinkage of nucleolus and cell organelles, signs of degeneration and also the auer-rods characteristic of AML are observed."} {"id": "PMID:1268336", "title": "[Electronic thrombocyte count from total blood].", "content": "Platelets were simultaneously counted in 52 persons by the conventional method of Cronkite and Brecher and with a new electronic cell volume analyser. The platelet counts estimated by the electronic analyser were 10% lower than that measured with the conventional method. This difference decreased to 1.5% when the same diluent was used for both methods. The described electronic counting method of platelets in whole blood is a simple procedure, which gives well reproducible and exact results.", "contents": "[Electronic thrombocyte count from total blood]. Platelets were simultaneously counted in 52 persons by the conventional method of Cronkite and Brecher and with a new electronic cell volume analyser. The platelet counts estimated by the electronic analyser were 10% lower than that measured with the conventional method. This difference decreased to 1.5% when the same diluent was used for both methods. The described electronic counting method of platelets in whole blood is a simple procedure, which gives well reproducible and exact results."} {"id": "PMID:1268337", "title": "Inhibitory activity of medium-dialyzed transfer factor on lymphocyte blastogenesis.", "content": "Human transfer factor was prepared from normal donors with marked skin reactivity against common microbial antigens by dialysis of lymphocyte extracts versus tissue culture medium (TFmd). Several batches of TFmd were tested for their ability to specifically increase the DNA synthesis of unsensitized lymphocytes in vitro in the presence of the corresponding antigens (PPD, SKSD, Candida, Thistoplasmin). No transfer or immunologic reactivity by TFmd was observed. There was, however, a significant unspecific inhibition by TFmd of lymphocyte cultures stimulated by antigens, PHA or allogeneic cells.", "contents": "Inhibitory activity of medium-dialyzed transfer factor on lymphocyte blastogenesis. Human transfer factor was prepared from normal donors with marked skin reactivity against common microbial antigens by dialysis of lymphocyte extracts versus tissue culture medium (TFmd). Several batches of TFmd were tested for their ability to specifically increase the DNA synthesis of unsensitized lymphocytes in vitro in the presence of the corresponding antigens (PPD, SKSD, Candida, Thistoplasmin). No transfer or immunologic reactivity by TFmd was observed. There was, however, a significant unspecific inhibition by TFmd of lymphocyte cultures stimulated by antigens, PHA or allogeneic cells."} {"id": "PMID:1268338", "title": "An auto-anti-b in an a1b person. Serological studies.", "content": "The serum of a patient (Mr. Lat) with the regular blood group A1 B contains an anti-B reacting with all cells having a B antigen except Bx and cis AB. The anti-B reacts at 4 degrees C and occasionally at room temperature as shown by agglutination, absorption-eluction and by thermo-dynamic assays. The antibody is regarded as an irregular autoantibody belonging to the group of the so called \"suppressed\" or \"latent\" antibodies.", "contents": "An auto-anti-b in an a1b person. Serological studies. The serum of a patient (Mr. Lat) with the regular blood group A1 B contains an anti-B reacting with all cells having a B antigen except Bx and cis AB. The anti-B reacts at 4 degrees C and occasionally at room temperature as shown by agglutination, absorption-eluction and by thermo-dynamic assays. The antibody is regarded as an irregular autoantibody belonging to the group of the so called \"suppressed\" or \"latent\" antibodies."} {"id": "PMID:1268339", "title": "P,p-DDT and p,p'-DDE effects on egg production, eggshell thickness, and reproduction of Japanese quail.", "content": "p,p' -DDT and p,p' -DDE were investigated for effects on egg production and eggshell thickness in Japanese quail. p,p' -DDT was examined for effects on hatchability and fertility. DDE was tested at 0, 2, 10, 40, and 200 ppm in the diet. No evidence suggested that DDE affected number of eggs laid, egg weight, or eggshell thickness at any level of DDE tested. DDT was tested at 1,2.5, 10 and 40 ppm in the diet. In one experiment, quail fed DDT at 40 ppm and caged in male-female pairs broke more eggs than quail caged similarly but fed lower amounts of DDT or than quail fed an equal amount of DDT but caged alone. DDT did not detectably reduce eggshell thickness, number of eggs laid, fertility, or hatchability. However, paired quail laid fewer eggs than did single quail in two experiments and laid eggs with thinner shells in one experiment.", "contents": "P,p-DDT and p,p'-DDE effects on egg production, eggshell thickness, and reproduction of Japanese quail. p,p' -DDT and p,p' -DDE were investigated for effects on egg production and eggshell thickness in Japanese quail. p,p' -DDT was examined for effects on hatchability and fertility. DDE was tested at 0, 2, 10, 40, and 200 ppm in the diet. No evidence suggested that DDE affected number of eggs laid, egg weight, or eggshell thickness at any level of DDE tested. DDT was tested at 1,2.5, 10 and 40 ppm in the diet. In one experiment, quail fed DDT at 40 ppm and caged in male-female pairs broke more eggs than quail caged similarly but fed lower amounts of DDT or than quail fed an equal amount of DDT but caged alone. DDT did not detectably reduce eggshell thickness, number of eggs laid, fertility, or hatchability. However, paired quail laid fewer eggs than did single quail in two experiments and laid eggs with thinner shells in one experiment."} {"id": "PMID:1268350", "title": "Antioxidant and antitranspirant protection of apple foliage against ozone injury.", "content": "Visible injury to apple foliage from exposure to ozone includes brown stippling on lower leaf surfaces and a light yellow mosaic on upper surfaces. Histologically, chlorophyll is destroyed and palisade and spongy mesophyll cells collapse following disintegration of their protoplasm. Foliar spray applications of the antioxidant, diphenylamine (DPA) or the antitranspirant, Wilt Pruf offer protection against this visible and histological injury. Superior protection results from application of both agents in combination.", "contents": "Antioxidant and antitranspirant protection of apple foliage against ozone injury. Visible injury to apple foliage from exposure to ozone includes brown stippling on lower leaf surfaces and a light yellow mosaic on upper surfaces. Histologically, chlorophyll is destroyed and palisade and spongy mesophyll cells collapse following disintegration of their protoplasm. Foliar spray applications of the antioxidant, diphenylamine (DPA) or the antitranspirant, Wilt Pruf offer protection against this visible and histological injury. Superior protection results from application of both agents in combination."} {"id": "PMID:1268361", "title": "Worker environment research. IV. The effect of dust derived from several soil types on the dissipation of parathion and paraoxon dislodgable residues on citrus foliage.", "content": "Parathion sorbed to dust can persist as dislodgable residues on citrus leaves. Semi-logarithmic plots of parathion dislodgable residue data were initially linear for the 6 soils studied and then a distinct change to lower rates occurred with 5 of the soils. As initial rates and the residue level at the rate change are dependent on the soil, foliar dust is implicated as a causative factor in the non-uniformity of residue dissipation rates. Soils can influence the conversion of parathion to paraoxon. Paraoxon levels differed greatly with the type of soil and were highest with Pike's Peak clay. Thus, its use in a parathion formulation could produce relatively high levels of paraoxon dislodgable residues. It is significant that, second to Pike's Peak clay, the highest total dislodgable residue level was found with Visalia silt loam which was collected from a grove where a worker poisoning episode had occurred in 1974.", "contents": "Worker environment research. IV. The effect of dust derived from several soil types on the dissipation of parathion and paraoxon dislodgable residues on citrus foliage. Parathion sorbed to dust can persist as dislodgable residues on citrus leaves. Semi-logarithmic plots of parathion dislodgable residue data were initially linear for the 6 soils studied and then a distinct change to lower rates occurred with 5 of the soils. As initial rates and the residue level at the rate change are dependent on the soil, foliar dust is implicated as a causative factor in the non-uniformity of residue dissipation rates. Soils can influence the conversion of parathion to paraoxon. Paraoxon levels differed greatly with the type of soil and were highest with Pike's Peak clay. Thus, its use in a parathion formulation could produce relatively high levels of paraoxon dislodgable residues. It is significant that, second to Pike's Peak clay, the highest total dislodgable residue level was found with Visalia silt loam which was collected from a grove where a worker poisoning episode had occurred in 1974."} {"id": "PMID:1268362", "title": "Effects of chitosan--a coagulating agent for food processing wastes--in the diets of rats on growth and liver and blood composition.", "content": "Effects of feeding free chitosan to rats at graded levels up to 15 percent of the diet for eight weeks was investigated. Animals receiving diets containing 5 percent or less of chitosan grew well at comparable rates. Progressive growth reduction occurred when chitosan was increased to 10 and 15 percent of the diet and enlargement of liver and kidneys was observed only in animals receiving the highest level of dietary chitosan. Liver moisture, protein, lipid, ash, and nucleic acids; blood hemoglobin and packed cell volume; and serum total protein, albumin, ceruloplasmin and transferrin were determined. Values for these components of liver and blood were altered significantly in the animals receiving the highest level of chitosan when compared to control animals. However, in animals receiving 5 percent or less of dietary chitosan none of these measures of tissue composition was different from controls, except for liver protein concentration of rats fed the 5 percent of chitosan diet. Animal feeds containing coagulated by-products are not expected to contain over 0.2% chitosan in the total diet. No adverse effects have been observed at this level in rat feeding studies. Therefore the tolerance level for dietary chitosan appears to be well above the levels expected to be in animal feeds containing by-products recovered from food processing wastes by coagulation with chitosan.", "contents": "Effects of chitosan--a coagulating agent for food processing wastes--in the diets of rats on growth and liver and blood composition. Effects of feeding free chitosan to rats at graded levels up to 15 percent of the diet for eight weeks was investigated. Animals receiving diets containing 5 percent or less of chitosan grew well at comparable rates. Progressive growth reduction occurred when chitosan was increased to 10 and 15 percent of the diet and enlargement of liver and kidneys was observed only in animals receiving the highest level of dietary chitosan. Liver moisture, protein, lipid, ash, and nucleic acids; blood hemoglobin and packed cell volume; and serum total protein, albumin, ceruloplasmin and transferrin were determined. Values for these components of liver and blood were altered significantly in the animals receiving the highest level of chitosan when compared to control animals. However, in animals receiving 5 percent or less of dietary chitosan none of these measures of tissue composition was different from controls, except for liver protein concentration of rats fed the 5 percent of chitosan diet. Animal feeds containing coagulated by-products are not expected to contain over 0.2% chitosan in the total diet. No adverse effects have been observed at this level in rat feeding studies. Therefore the tolerance level for dietary chitosan appears to be well above the levels expected to be in animal feeds containing by-products recovered from food processing wastes by coagulation with chitosan."} {"id": "PMID:1268365", "title": "90 day dermal toxicity of DDVP in male rats.", "content": "Exposure of male rats to DDVP (21.4 mg/kg/day) through dermal painting for a period of 90 days did not produce any changes in skin or testis. None of the animals showed any clinical symptoms of DDVP poisoning or mortality during experimentation. Rapid degradation of DDVP and further its detoification in in liver of rats and other species of mammals seems to be the prime reason for the non-toxic effect of the insecticide.", "contents": "90 day dermal toxicity of DDVP in male rats. Exposure of male rats to DDVP (21.4 mg/kg/day) through dermal painting for a period of 90 days did not produce any changes in skin or testis. None of the animals showed any clinical symptoms of DDVP poisoning or mortality during experimentation. Rapid degradation of DDVP and further its detoification in in liver of rats and other species of mammals seems to be the prime reason for the non-toxic effect of the insecticide."} {"id": "PMID:1268367", "title": "On effect of chlordane on the blood glucose and of glucose administration on the acute chlordane toxicity in Meriones hurrianae Jerdon, the indian desert gerbil.", "content": "The effect of 25, 50 and 75 mg/kg body wt. chlordane on the blood glucose level and of glucose administration in chlordane intoxicated Indian desert gerbils are investigated. Chlordane produces hyperglycemia and lowers the glucose tolerance indicating an impairment in the uptake and utilization of glucose in intoxicated gerbils. The possible reasons for these effects are discussed.", "contents": "On effect of chlordane on the blood glucose and of glucose administration on the acute chlordane toxicity in Meriones hurrianae Jerdon, the indian desert gerbil. The effect of 25, 50 and 75 mg/kg body wt. chlordane on the blood glucose level and of glucose administration in chlordane intoxicated Indian desert gerbils are investigated. Chlordane produces hyperglycemia and lowers the glucose tolerance indicating an impairment in the uptake and utilization of glucose in intoxicated gerbils. The possible reasons for these effects are discussed."} {"id": "PMID:1268369", "title": "Acute toxicity of ammonia-base neutral sulfite pulp mill waste liquor to rainbow trout.", "content": "The acute toxicity to rainbow trout of untreated ammonia-base neutral sulfite pulp mill waste liquor was demonstrated in these experimants. A mean LC50 of 0.82% and 95% confidence interval of 0.08 - 1.56% was obtained in four static bioassays. Lignin, sulfur dioxide, and ammonia were implicated as toxic components. The latter two were probably the most toxic.", "contents": "Acute toxicity of ammonia-base neutral sulfite pulp mill waste liquor to rainbow trout. The acute toxicity to rainbow trout of untreated ammonia-base neutral sulfite pulp mill waste liquor was demonstrated in these experimants. A mean LC50 of 0.82% and 95% confidence interval of 0.08 - 1.56% was obtained in four static bioassays. Lignin, sulfur dioxide, and ammonia were implicated as toxic components. The latter two were probably the most toxic."} {"id": "PMID:1268435", "title": "Breast augmentation with gluteal dermofat grafts: a 5-10 year follow-up.", "content": "Of a series of 3 dermofat grafts, about a quarter had either to be removed or disappeared completely, while the remainder shrank unpredictably and were all calcified by the end of 4 years. The donor site on the buttock was often unsightly.", "contents": "Breast augmentation with gluteal dermofat grafts: a 5-10 year follow-up. Of a series of 3 dermofat grafts, about a quarter had either to be removed or disappeared completely, while the remainder shrank unpredictably and were all calcified by the end of 4 years. The donor site on the buttock was often unsightly."} {"id": "PMID:1268441", "title": "Selective neurectomies to achieve symmetry in partial and complete facial paralysis.", "content": "Experience with selective facial neurectomies, in partial and total palsies, is reported. If under careful control by faradic stimulation the area to be weakened is conpletely, and the neighbouring musculature partly denervated, consistently satisfactory results can be predicted. Evidence suggests that rather than recovery of motion by axon regeneration, there is a marked tendency for collateral regeneration of peripheral facial nerve fibres from muscles left intact, into denervated muscles.", "contents": "Selective neurectomies to achieve symmetry in partial and complete facial paralysis. Experience with selective facial neurectomies, in partial and total palsies, is reported. If under careful control by faradic stimulation the area to be weakened is conpletely, and the neighbouring musculature partly denervated, consistently satisfactory results can be predicted. Evidence suggests that rather than recovery of motion by axon regeneration, there is a marked tendency for collateral regeneration of peripheral facial nerve fibres from muscles left intact, into denervated muscles."} {"id": "PMID:1268447", "title": "Assessment of the influence of the timing of repair on flexor tendon injuries in chickens.", "content": "The flexor tendons of the middle toes of chickens were divided and the flexor profundus repaired after varying intervals up to 6 weeks. The best results were obtained with repairs within a few hours, the next best with repairs any time after the 10th day and the worst with repairs between the 4th and 7th days.", "contents": "Assessment of the influence of the timing of repair on flexor tendon injuries in chickens. The flexor tendons of the middle toes of chickens were divided and the flexor profundus repaired after varying intervals up to 6 weeks. The best results were obtained with repairs within a few hours, the next best with repairs any time after the 10th day and the worst with repairs between the 4th and 7th days."} {"id": "PMID:1268448", "title": "Quantity conceptions in university students: another look.", "content": "One hundred and thirty-eight post-graduate students enrolled in a Diploma in Education course were tested for their ability to converse weight and volume. A methodological criticism of the earlier work or Elkind (1962) and Towler & Wheatley (1971) is offered which casts doubt on the extremely high proportion of non-conservers of volume reported in those studies. Nevertheless, using a modified version of Elkind's methodology, 18 per cent of our sample were non-conservers of volume, a result providing some support for the generaltiy of Elkind's findings. The results are discussed under the four headings of horizontal decalage, sex differences, possible effects of pre-graduate courses of study and educational implications. The importance of the individual as constructor and interpreter of his own experience is emphasized.", "contents": "Quantity conceptions in university students: another look. One hundred and thirty-eight post-graduate students enrolled in a Diploma in Education course were tested for their ability to converse weight and volume. A methodological criticism of the earlier work or Elkind (1962) and Towler & Wheatley (1971) is offered which casts doubt on the extremely high proportion of non-conservers of volume reported in those studies. Nevertheless, using a modified version of Elkind's methodology, 18 per cent of our sample were non-conservers of volume, a result providing some support for the generaltiy of Elkind's findings. The results are discussed under the four headings of horizontal decalage, sex differences, possible effects of pre-graduate courses of study and educational implications. The importance of the individual as constructor and interpreter of his own experience is emphasized."} {"id": "PMID:1268449", "title": "Inspection time and measured intelligence.", "content": "Ten subjects with WAIS Full Scale IQ scores ranging from 119 to 47 were required to discriminate between two lines of markedly different length, exposed in random order for ten different durations, by pressing one of two keys. Estimates of inspection time gamma, the rate at which sensory input is accumulated and passed to subsequent decision processes, were calculated directly from the psychometric functions obtained gamma was found to correlate negatively with subtests contributing to Performance IQ. There was a substantial degree of consistency between estimates of gamma on two different occasions and training did not appear to affect the index, although differences between the two estimates increased as the value of the first estimate increased. Mean overall response latency did not correlate significantly with intelligence and measures obtained from retarded subjects were very like those reported in similar experimental situations utilizing normal subjects. This unexpected finding is interpreted as suggesting that, in this situation, retarded subjects have been prepared to respond on the basis of less evidence than is usually required by intellectually normal subjects.", "contents": "Inspection time and measured intelligence. Ten subjects with WAIS Full Scale IQ scores ranging from 119 to 47 were required to discriminate between two lines of markedly different length, exposed in random order for ten different durations, by pressing one of two keys. Estimates of inspection time gamma, the rate at which sensory input is accumulated and passed to subsequent decision processes, were calculated directly from the psychometric functions obtained gamma was found to correlate negatively with subtests contributing to Performance IQ. There was a substantial degree of consistency between estimates of gamma on two different occasions and training did not appear to affect the index, although differences between the two estimates increased as the value of the first estimate increased. Mean overall response latency did not correlate significantly with intelligence and measures obtained from retarded subjects were very like those reported in similar experimental situations utilizing normal subjects. This unexpected finding is interpreted as suggesting that, in this situation, retarded subjects have been prepared to respond on the basis of less evidence than is usually required by intellectually normal subjects."} {"id": "PMID:1268450", "title": "Some evidence for 'speech' as an acoustic feature.", "content": "Under conditions of serial recall of auditorily presented lists of digits, recall of the last item has been shown to be adversely affected by the presence of a redundant item following the list. This is known as 'the suffix effect' (Crowder & Morton, 1969). In a series of experiments it is shown that the size of this effect is not influenced by the phonological complexity of the suffix. Non-speech sounds, on the other hand, produce no suffix effect even when the subjects are forced to process them. Certain speech sounds were also found to produce no effect. It is concluded that these sounds lacked properties which are characteristic of speech sounds and so were classified as 'non-speech' and that as a result, these sounds are processed by a separate system from the speech sounds.", "contents": "Some evidence for 'speech' as an acoustic feature. Under conditions of serial recall of auditorily presented lists of digits, recall of the last item has been shown to be adversely affected by the presence of a redundant item following the list. This is known as 'the suffix effect' (Crowder & Morton, 1969). In a series of experiments it is shown that the size of this effect is not influenced by the phonological complexity of the suffix. Non-speech sounds, on the other hand, produce no suffix effect even when the subjects are forced to process them. Certain speech sounds were also found to produce no effect. It is concluded that these sounds lacked properties which are characteristic of speech sounds and so were classified as 'non-speech' and that as a result, these sounds are processed by a separate system from the speech sounds."} {"id": "PMID:1268451", "title": "Extraversion and reinforcement in verbal operant conditioning.", "content": "The present investigation was designed to study the relationship between extraversion and modes of reinforcement in verbal operant conditioning. A 4 X 3 randomized block design was replicated ten times. Eighty graduate and post-graduate male students were individually subjected to the standard Taffel conditioning procedure. When the numbers of conditioned responses produced by introverts and extraverts were compared, it was found that: (1) under negative reinforcement ('bad' and electric shock), with both the female and male experimenters, and under positive reinforcement ('good') with the male experimenter, the introverts' score was the higher of the two; (2) under positive reinforcement ('good') with the female experimenter, the extraverts' score was higher than that of the introverts.", "contents": "Extraversion and reinforcement in verbal operant conditioning. The present investigation was designed to study the relationship between extraversion and modes of reinforcement in verbal operant conditioning. A 4 X 3 randomized block design was replicated ten times. Eighty graduate and post-graduate male students were individually subjected to the standard Taffel conditioning procedure. When the numbers of conditioned responses produced by introverts and extraverts were compared, it was found that: (1) under negative reinforcement ('bad' and electric shock), with both the female and male experimenters, and under positive reinforcement ('good') with the male experimenter, the introverts' score was the higher of the two; (2) under positive reinforcement ('good') with the female experimenter, the extraverts' score was higher than that of the introverts."} {"id": "PMID:1268452", "title": "Extraversion, activation and the recall of prose.", "content": "Subjects were divided into four groups on the basis of their scores on the extraversion scale of the Eysenck Personality Inventory and the general activation scale of Thayer's Activation-Deactivation Adjective Check List. A prose passage was presented to subjects who then attempted to recall it under strict instructions to avoid errors. There were significant interactions between activation and extraversion for the error data, and the phrase-correct data, with moderate levels of arousal (high activation extraverts and low activation introverts) being associated with the fewest errors and the most phrases correctly recalled. It was concluded that the study showed the importance of arousal to recall performance, possibly due to the effects of arousal on retrieval processes.", "contents": "Extraversion, activation and the recall of prose. Subjects were divided into four groups on the basis of their scores on the extraversion scale of the Eysenck Personality Inventory and the general activation scale of Thayer's Activation-Deactivation Adjective Check List. A prose passage was presented to subjects who then attempted to recall it under strict instructions to avoid errors. There were significant interactions between activation and extraversion for the error data, and the phrase-correct data, with moderate levels of arousal (high activation extraverts and low activation introverts) being associated with the fewest errors and the most phrases correctly recalled. It was concluded that the study showed the importance of arousal to recall performance, possibly due to the effects of arousal on retrieval processes."} {"id": "PMID:1268453", "title": "Memory deficits in early infantile autism: some similarities to the amnesic syndrome.", "content": "Autistic children were compared with control children on tasks in which retention was tested by different methods. In three tests of recall, using named pictures, written words and spoken words as test stimuli, autistic children were impaired in comparison with age-matched normal children and with controls matched for verbal ability. In one test of forced-choice recognition of pictures, autistic children were impaired in comparison with ability-matched controls. In three tests of cued recall, using named pictures, written words and spoken words as test stimuli, and acoustic, graphemic and semantic cues, autistic children were not impaired in comparison with normal age-matched controls. In one test of paired-associate learning using non-related word pairs as test stimuli autistic children were not impaired in comparison with normal age-matched controls. These experimental paradigms were similar to some that have been used to investigate the amnesic syndrome in man. Thus findings on paired-associate learning differ in autistic and amnesic subjects, but findings on recall, recognition and cued recall are comparable. A possible parallel between autism and amnesia is discussed.", "contents": "Memory deficits in early infantile autism: some similarities to the amnesic syndrome. Autistic children were compared with control children on tasks in which retention was tested by different methods. In three tests of recall, using named pictures, written words and spoken words as test stimuli, autistic children were impaired in comparison with age-matched normal children and with controls matched for verbal ability. In one test of forced-choice recognition of pictures, autistic children were impaired in comparison with ability-matched controls. In three tests of cued recall, using named pictures, written words and spoken words as test stimuli, and acoustic, graphemic and semantic cues, autistic children were not impaired in comparison with normal age-matched controls. In one test of paired-associate learning using non-related word pairs as test stimuli autistic children were not impaired in comparison with normal age-matched controls. These experimental paradigms were similar to some that have been used to investigate the amnesic syndrome in man. Thus findings on paired-associate learning differ in autistic and amnesic subjects, but findings on recall, recognition and cued recall are comparable. A possible parallel between autism and amnesia is discussed."} {"id": "PMID:1268454", "title": "Constraints on classificatory skills in young children.", "content": "On three occasions over a one-year period 23 children aged 3-4 were asked to match target objects with other objects which were similar to the target in shape or in colour but not in both. A sequence of matches to each target was asked for. The structure of these sequences is examined for evidence of classifacatory abilities. Many subjects appear to be attempting (not always successfully) to follow a strategy of 'holding fast' to their original choice of matching criterion (colour or shape) on subsequent trials. The striking differences between performance after a first-trial colour-match and after a first-trial shape-match are described. It is argued that development during this period involves an increasing ability to ignore the more salient attribute (shape) when matching by colour. The general developmental significance is discussed.", "contents": "Constraints on classificatory skills in young children. On three occasions over a one-year period 23 children aged 3-4 were asked to match target objects with other objects which were similar to the target in shape or in colour but not in both. A sequence of matches to each target was asked for. The structure of these sequences is examined for evidence of classifacatory abilities. Many subjects appear to be attempting (not always successfully) to follow a strategy of 'holding fast' to their original choice of matching criterion (colour or shape) on subsequent trials. The striking differences between performance after a first-trial colour-match and after a first-trial shape-match are described. It is argued that development during this period involves an increasing ability to ignore the more salient attribute (shape) when matching by colour. The general developmental significance is discussed."} {"id": "PMID:1268456", "title": "Uric acid disorders in patients with calcium stones.", "content": "Plasma and uric acid levels were measured in 132 men with calcium-containing renal stones and in 24 healthy men of similar ages. Fasting resulted in a significant fall in the mean plasma uric acid level of normal subjects. Intermittent hyperuricaemia was observed in 7% of fasting patients. Intermittent hyperuricosuria was found in 17% of non-fasting patients but in only 2 to 6% of fasting subjects. Most of the uric acid abnormalities in patients with calcium stones therefore appear to be due to diet and may be prevented by reducing the consumption of purine-rich foods. A direct relationship was observed between uric acid excretion and urine flow at normal flow rates. It is suggested that the apparent increase in stone incidence, which occurs with rising living standards, may be due partly to increased consumption of purine-rich foods.", "contents": "Uric acid disorders in patients with calcium stones. Plasma and uric acid levels were measured in 132 men with calcium-containing renal stones and in 24 healthy men of similar ages. Fasting resulted in a significant fall in the mean plasma uric acid level of normal subjects. Intermittent hyperuricaemia was observed in 7% of fasting patients. Intermittent hyperuricosuria was found in 17% of non-fasting patients but in only 2 to 6% of fasting subjects. Most of the uric acid abnormalities in patients with calcium stones therefore appear to be due to diet and may be prevented by reducing the consumption of purine-rich foods. A direct relationship was observed between uric acid excretion and urine flow at normal flow rates. It is suggested that the apparent increase in stone incidence, which occurs with rising living standards, may be due partly to increased consumption of purine-rich foods."} {"id": "PMID:1268458", "title": "The elastic component of normal and dilated ureters in children: chemical and histochemical characterisation.", "content": "Using chemical and histochemical techniques, it has been possible to calculate the exact amount and distribution of the elastin in normal and abnormal ureters in children. From the quantitative analyses, it has been calculated that in the dilated ureters the elastin content represents the 3% to 5% of the organic material, while in the normal ureters it is less than 1%.", "contents": "The elastic component of normal and dilated ureters in children: chemical and histochemical characterisation. Using chemical and histochemical techniques, it has been possible to calculate the exact amount and distribution of the elastin in normal and abnormal ureters in children. From the quantitative analyses, it has been calculated that in the dilated ureters the elastin content represents the 3% to 5% of the organic material, while in the normal ureters it is less than 1%."} {"id": "PMID:1268460", "title": "Experience with the ileal ureter.", "content": "The isolated ileal loop often provides a satisfactory solution to the problem of extensive ureteric defects. Our experience in 18 cases of diseased ureters partially or totally replaced by isolated ileal loops is presented. The indications for the operation and important operative and preoperative details are discussed. The operation presents a definite method for renal conservation in many cases in which nephrectomy would otherwise have been unavoidable.", "contents": "Experience with the ileal ureter. The isolated ileal loop often provides a satisfactory solution to the problem of extensive ureteric defects. Our experience in 18 cases of diseased ureters partially or totally replaced by isolated ileal loops is presented. The indications for the operation and important operative and preoperative details are discussed. The operation presents a definite method for renal conservation in many cases in which nephrectomy would otherwise have been unavoidable."} {"id": "PMID:1268461", "title": "Endometriosis mimicking ureterolithiasis.", "content": "A case of endometriosis obstructing the right ureter is described, with a clinical picture mimicking ureterolithiasis. The usefulness of rapid sequence camera-scintigram in the early diagnosis of ureteral obstruction is discussed.", "contents": "Endometriosis mimicking ureterolithiasis. A case of endometriosis obstructing the right ureter is described, with a clinical picture mimicking ureterolithiasis. The usefulness of rapid sequence camera-scintigram in the early diagnosis of ureteral obstruction is discussed."} {"id": "PMID:1268462", "title": "Re-implantation of the ureter.", "content": "For 10 years a modified Politano-Leadbetter technique with extravesical as well as intravesical exposure has been used for re-implantation of the ureter. The results suggest that the passive mechanism of prevention of reflux is more important than any active mechanism and that it is unnecessary to excise the lower end of the ureter.", "contents": "Re-implantation of the ureter. For 10 years a modified Politano-Leadbetter technique with extravesical as well as intravesical exposure has been used for re-implantation of the ureter. The results suggest that the passive mechanism of prevention of reflux is more important than any active mechanism and that it is unnecessary to excise the lower end of the ureter."} {"id": "PMID:1268467", "title": "Urinary citrate excretion in stone-formers and normal controls.", "content": "A specific method was used for the estimation of citrate in 24-hour urine collections from 108 young adult controls, 158 patient controls and 164 stone-formers. Stone-formers excreted significantly less citrate in 24 hours than either patient controls or young adult controls. Stone-formers had a lower concentration of citrate in their urine than either of the control groups. The young adult females exhibited a much greater excretion of citrate relative to calcium than the young males. Because of the ability of citrate to complex with calcium ions and keep them in solution, the relatively low incidence of calcium-containing stones in females under 50 years of age could well be the result of their high excretion of citrate and their increased excretion of this substance relative to calcium.", "contents": "Urinary citrate excretion in stone-formers and normal controls. A specific method was used for the estimation of citrate in 24-hour urine collections from 108 young adult controls, 158 patient controls and 164 stone-formers. Stone-formers excreted significantly less citrate in 24 hours than either patient controls or young adult controls. Stone-formers had a lower concentration of citrate in their urine than either of the control groups. The young adult females exhibited a much greater excretion of citrate relative to calcium than the young males. Because of the ability of citrate to complex with calcium ions and keep them in solution, the relatively low incidence of calcium-containing stones in females under 50 years of age could well be the result of their high excretion of citrate and their increased excretion of this substance relative to calcium."} {"id": "PMID:1268470", "title": "A study of concentrations of trimethoprim-sulphamethoxazole in the human prostate gland.", "content": "The ability of trimethoprim (TMP) and sulphamethoxazole (SMX) components of co-trimoxazole to penetrate the human prostate gland was investigated. After a single 4-tablet dose TMP was evenly distributed between prostate and plasma, whereas SMX was mainly associated with plasma. Following a week's therapy significant accumulation of TMP was seen in the prostate relative to plasma whereas SMX although still associated with plasma had increased drug levels in prostate compared with the single dose study. It is concluded that co-trimoxazole produces effective antibacterial levels in the human prostate and has indications in the treatment of prostatitis.", "contents": "A study of concentrations of trimethoprim-sulphamethoxazole in the human prostate gland. The ability of trimethoprim (TMP) and sulphamethoxazole (SMX) components of co-trimoxazole to penetrate the human prostate gland was investigated. After a single 4-tablet dose TMP was evenly distributed between prostate and plasma, whereas SMX was mainly associated with plasma. Following a week's therapy significant accumulation of TMP was seen in the prostate relative to plasma whereas SMX although still associated with plasma had increased drug levels in prostate compared with the single dose study. It is concluded that co-trimoxazole produces effective antibacterial levels in the human prostate and has indications in the treatment of prostatitis."} {"id": "PMID:1268472", "title": "Badenoch's pull-through operation for urethral stricture.", "content": "14 patients with strictures in the region of the membranous urethra were treated by Badenoch's urethral pull-through operation or a slight modification of this. The results were good in 10 of the cases. This procedure has advantages over those using scrotal flaps in hot climates.", "contents": "Badenoch's pull-through operation for urethral stricture. 14 patients with strictures in the region of the membranous urethra were treated by Badenoch's urethral pull-through operation or a slight modification of this. The results were good in 10 of the cases. This procedure has advantages over those using scrotal flaps in hot climates."} {"id": "PMID:1268473", "title": "Thyroidectomy for non-familial medullary carcinoma.", "content": "Two cases of non-familial medullary carcinoma of the thyroid which had thyroid tissue remaining after initial thyroidectomy were shown to contain residual, intra-glandular carcinoma at reoperation. This observation, the distribution of C cells in the normal thyroid gland and the lymph node spread of this carcinoma have led to the proposal of a bilateral 90 per cent upper pole thyroidectomy including the superior parathyroids for cases of non-familial medullary carcinoma. This operation removes all the C-cell-bearing area and leaves a small thyroid remnant at the lower pole for preservation of the inferior parathyroid glands. The operation is discussed with reference to these factors.", "contents": "Thyroidectomy for non-familial medullary carcinoma. Two cases of non-familial medullary carcinoma of the thyroid which had thyroid tissue remaining after initial thyroidectomy were shown to contain residual, intra-glandular carcinoma at reoperation. This observation, the distribution of C cells in the normal thyroid gland and the lymph node spread of this carcinoma have led to the proposal of a bilateral 90 per cent upper pole thyroidectomy including the superior parathyroids for cases of non-familial medullary carcinoma. This operation removes all the C-cell-bearing area and leaves a small thyroid remnant at the lower pole for preservation of the inferior parathyroid glands. The operation is discussed with reference to these factors."} {"id": "PMID:1268474", "title": "Biopsy of the impalpable breast lesion detected by mammography.", "content": "Specimen radiology plays an essential part in the surgical management of the impalpable breast lesion detected by mammography. It also plays a necessary part in the complete pathological examination of the specimen. A method for preoperative localization of the mammographically detected impalpable breast lesion is described.", "contents": "Biopsy of the impalpable breast lesion detected by mammography. Specimen radiology plays an essential part in the surgical management of the impalpable breast lesion detected by mammography. It also plays a necessary part in the complete pathological examination of the specimen. A method for preoperative localization of the mammographically detected impalpable breast lesion is described."} {"id": "PMID:1268475", "title": "The association of duodenogastric reflux with dumping and gastric retention.", "content": "Gastric emptying of solid and liquid meals together with duodenogastric reflux has been measured in a prospective trial of proximal gastric vagotomy and truncal vagotomy and antrectomy. Three abnormalities of motility associated with postoperative symptoms have been defined. If more than one abnormality was present in an individual there was an 80 per cent incidence of associated symptoms. Proximal gastric vagotomy produced significantly fewer abnormalities of gastro-duodenal motility than did truncal vagotomy and antrectomy.", "contents": "The association of duodenogastric reflux with dumping and gastric retention. Gastric emptying of solid and liquid meals together with duodenogastric reflux has been measured in a prospective trial of proximal gastric vagotomy and truncal vagotomy and antrectomy. Three abnormalities of motility associated with postoperative symptoms have been defined. If more than one abnormality was present in an individual there was an 80 per cent incidence of associated symptoms. Proximal gastric vagotomy produced significantly fewer abnormalities of gastro-duodenal motility than did truncal vagotomy and antrectomy."} {"id": "PMID:1268476", "title": "Subphrenic abscess: a study of 241 patients at the Royal Prince Edward Hospital, 1950-73.", "content": "A series of 241 patients with subphrenic abscess was analysed to seek reasons for the continuing mortality. Aspects of pathology, clinical presentation, special investigations and management were affected by therapy with broad spectrum antibiotics to make diagnosis more difficult, particularly in relation to left subphrenic abscesses. When transperitoneal exploration and drainage were employed, high morbidity and mortality resulted. Satisfactory results followed extraserous drainage. The introduction of parenteral hyperalimentation promised control fistulas associated with abscesses, a situation hitherto associated with a poor prognosis.", "contents": "Subphrenic abscess: a study of 241 patients at the Royal Prince Edward Hospital, 1950-73. A series of 241 patients with subphrenic abscess was analysed to seek reasons for the continuing mortality. Aspects of pathology, clinical presentation, special investigations and management were affected by therapy with broad spectrum antibiotics to make diagnosis more difficult, particularly in relation to left subphrenic abscesses. When transperitoneal exploration and drainage were employed, high morbidity and mortality resulted. Satisfactory results followed extraserous drainage. The introduction of parenteral hyperalimentation promised control fistulas associated with abscesses, a situation hitherto associated with a poor prognosis."} {"id": "PMID:1268477", "title": "Salvage of the lower limb.", "content": "This is a retrospective study of 80 patients with 94 severely ischaemic lower limbs treated over a period of 6 years. Arterial reconstruction was possible in 47 patients (54 limbs) and 76 per cent of these limbs were salvaged. There was no operative mortality. An attempt has been made to analyse the reasons for the failure. The fate of the patients who underwent major amputation is described. The selection of patients for direct arterial surgery is discussed, together with some of the technical problems involved.", "contents": "Salvage of the lower limb. This is a retrospective study of 80 patients with 94 severely ischaemic lower limbs treated over a period of 6 years. Arterial reconstruction was possible in 47 patients (54 limbs) and 76 per cent of these limbs were salvaged. There was no operative mortality. An attempt has been made to analyse the reasons for the failure. The fate of the patients who underwent major amputation is described. The selection of patients for direct arterial surgery is discussed, together with some of the technical problems involved."} {"id": "PMID:1268478", "title": "The clinical significance of venous thrombosis of the calf.", "content": "A total of 379 general surgical and hip replacement patients were studied with the radioactive fibrinogen uptake test and the Doppler ultrasound flow detector to determine the incidence and natural history of postoperative deep vein thrombosis (DVT) in their lower limbs. The overall incidence of DVT was 33 per cent, but clinical follow-up indicated that the great majority of these patients suffered no ill effects. It is concluded that thrombosis diagnosed by the radioactive fibrinogen uptake test is of very limited clinical significance and that the technique cannot be recommended as a screening test for DVT.", "contents": "The clinical significance of venous thrombosis of the calf. A total of 379 general surgical and hip replacement patients were studied with the radioactive fibrinogen uptake test and the Doppler ultrasound flow detector to determine the incidence and natural history of postoperative deep vein thrombosis (DVT) in their lower limbs. The overall incidence of DVT was 33 per cent, but clinical follow-up indicated that the great majority of these patients suffered no ill effects. It is concluded that thrombosis diagnosed by the radioactive fibrinogen uptake test is of very limited clinical significance and that the technique cannot be recommended as a screening test for DVT."} {"id": "PMID:1268479", "title": "The prognosis after surgical treatment for carcinoma of the rectum.", "content": "The results of surgical treatment of 550 cases of carcinoma of the rectum presenting to the Professorial Surgical Unit of the General Infirmary, Leeds, from 1955 to 1968 have been analysed.", "contents": "The prognosis after surgical treatment for carcinoma of the rectum. The results of surgical treatment of 550 cases of carcinoma of the rectum presenting to the Professorial Surgical Unit of the General Infirmary, Leeds, from 1955 to 1968 have been analysed."} {"id": "PMID:1268480", "title": "Rectal sphincter reconstruction in perineal colostomies after abdominoperineal resection for cancer.", "content": "A surgical technique is proposed for the reconstruction of the anal sphincter in perineal colostomies after abdominoperineal resection for cancer. The procedure, which employs the gracilis muscle for the sphincteric reconstruction is described and the operative results and complications are analysed in 24 patients submitted to this type of surgery. Of the 22 patients who were followed up, 17 had excellent or good results with retention of solid or soft stools. Three patients had poor results with no voluntary retention, while 2 others were partly incontinent of solid faeces. In this group of 5 patients, 3 had stenosis of the colostomy and 1 had no sensibility of impending defaecation.", "contents": "Rectal sphincter reconstruction in perineal colostomies after abdominoperineal resection for cancer. A surgical technique is proposed for the reconstruction of the anal sphincter in perineal colostomies after abdominoperineal resection for cancer. The procedure, which employs the gracilis muscle for the sphincteric reconstruction is described and the operative results and complications are analysed in 24 patients submitted to this type of surgery. Of the 22 patients who were followed up, 17 had excellent or good results with retention of solid or soft stools. Three patients had poor results with no voluntary retention, while 2 others were partly incontinent of solid faeces. In this group of 5 patients, 3 had stenosis of the colostomy and 1 had no sensibility of impending defaecation."} {"id": "PMID:1268481", "title": "Jaundice and wound healing: an experimental study.", "content": "Obstructive jaundice was induced in rats by ligation and division of the common bile duct. The healing of a standard gastric incision and a parietal peritoneal defect in these animals showed histological evidence of delayed healing compared with controls. The bursting strength of the abdominal incision was also lowered, but not that of the stomach, probably because of the adhesions which reinforced the gastric incisions. Angiography did, however, reveal delay in angiogenesis in the gastric wounds of jaundiced animals. The possible causes of this delay in healing and its clinical implications require further investigations.", "contents": "Jaundice and wound healing: an experimental study. Obstructive jaundice was induced in rats by ligation and division of the common bile duct. The healing of a standard gastric incision and a parietal peritoneal defect in these animals showed histological evidence of delayed healing compared with controls. The bursting strength of the abdominal incision was also lowered, but not that of the stomach, probably because of the adhesions which reinforced the gastric incisions. Angiography did, however, reveal delay in angiogenesis in the gastric wounds of jaundiced animals. The possible causes of this delay in healing and its clinical implications require further investigations."} {"id": "PMID:1268482", "title": "The results of colostomy closure.", "content": "Complications arouse in 93 (44 per cent) of 213 patients following the closure of a temporary colostomy. These complications include 1 death, 19 faecal fistulas, 3 large bowel obstructions and 24 incisional hernias. Complications were most commonly seen following closure of colostomies of the sigmoid colon, especially when such closure was undertaken between the fourth and twelfth weeks after definite surgery. It is concluded that still greater care is needed in both the operative technique and the preoperative care of these patients.", "contents": "The results of colostomy closure. Complications arouse in 93 (44 per cent) of 213 patients following the closure of a temporary colostomy. These complications include 1 death, 19 faecal fistulas, 3 large bowel obstructions and 24 incisional hernias. Complications were most commonly seen following closure of colostomies of the sigmoid colon, especially when such closure was undertaken between the fourth and twelfth weeks after definite surgery. It is concluded that still greater care is needed in both the operative technique and the preoperative care of these patients."} {"id": "PMID:1268483", "title": "Manometric studies of anorectal disorders in infancy and childhood: an investigation of the physiopathology of continence and defaecation.", "content": "Anorectal manometry was performed on 126 infants and children with anorectal dosorders. In addition, 14 normal children were studied. Pressure measurements were taken with two perfused open-tip catheters. The activity of the external and internal balloon was used to distend the rectal ampulla with air.", "contents": "Manometric studies of anorectal disorders in infancy and childhood: an investigation of the physiopathology of continence and defaecation. Anorectal manometry was performed on 126 infants and children with anorectal dosorders. In addition, 14 normal children were studied. Pressure measurements were taken with two perfused open-tip catheters. The activity of the external and internal balloon was used to distend the rectal ampulla with air."} {"id": "PMID:1268484", "title": "The hydraulic impedance of the lower limb: its relevance to the success of bypass operations for occlusion of the superficial femoral artery.", "content": "Simultaneous measurements of pressure and flow waves were made in the course of 25 femoropopliteal bypass operations. From these measurements the the hydraulic impedance of the arterial system in the lower limb was calculated. The values obtained were correlated with the results of the operations. Although reconstruction reduced the impedance we were unable to predict accurately the probable result of the operation on the basis of these measurements. The results suggest that success is more closely related to a good collateral circulation than to \"run off\".", "contents": "The hydraulic impedance of the lower limb: its relevance to the success of bypass operations for occlusion of the superficial femoral artery. Simultaneous measurements of pressure and flow waves were made in the course of 25 femoropopliteal bypass operations. From these measurements the the hydraulic impedance of the arterial system in the lower limb was calculated. The values obtained were correlated with the results of the operations. Although reconstruction reduced the impedance we were unable to predict accurately the probable result of the operation on the basis of these measurements. The results suggest that success is more closely related to a good collateral circulation than to \"run off\"."} {"id": "PMID:1268485", "title": "Impedance plethysmography: evaluation of a simplified system of electrodes for the measurement of blood flow in the lower limb.", "content": "Venous occlusion plethysmography was used to measure the flow of blood into the lower limbs of 30 normal volunteers. An impedance plethysmograph, using disposable point electrodes, was compared with a mercury in Silastic strain gauge plethysmograph in 20 subjects. The effect of changes in the configuration of the point electrodes was studied in 10 subjects. Impedance plethysmography was shown to be reproducible, and one particular configuration of point electrodes was shown to be superior to the others.", "contents": "Impedance plethysmography: evaluation of a simplified system of electrodes for the measurement of blood flow in the lower limb. Venous occlusion plethysmography was used to measure the flow of blood into the lower limbs of 30 normal volunteers. An impedance plethysmograph, using disposable point electrodes, was compared with a mercury in Silastic strain gauge plethysmograph in 20 subjects. The effect of changes in the configuration of the point electrodes was studied in 10 subjects. Impedance plethysmography was shown to be reproducible, and one particular configuration of point electrodes was shown to be superior to the others."} {"id": "PMID:1268490", "title": "Myocardial infarction: a comparison between home and hospital care for patients.", "content": "To compare the results of home and hospital treatment in men aged under 70 years who had suffered acute myocardial infarction within 48 hours 1895 patients were considered for study in four centres in south-west England. Four-hundred-and-fifty patients were randomly allocated to receive care either at home by their family doctor or in hospital, initially in an intensive care unit. The randomised treatment groups were similar in age, history of cardiovascular disease, and incidence of hypotension when first examined. They were followed up for up to a year after onset. The mortality rate at 28 days was 12% for the random home group and 14% for the random hospital group; the corresponding figures at 330 days were 20% and 27%. On average, older patients and those without initial hypotension fared rather better under home care. The patients who underwent randomisation were similar to those whose place of care was not randomised, except that the non-randomised group contained a higher proportion of initially hypotensive patients, whose prognosis was poor wherever treated. These results confirm and extend our preliminary findings. Home care is a proper form of treatment for many patients with acute myocardial infarction, particularly those over 60 years and those with an uncomplicated attack seen by general practitioners.", "contents": "Myocardial infarction: a comparison between home and hospital care for patients. To compare the results of home and hospital treatment in men aged under 70 years who had suffered acute myocardial infarction within 48 hours 1895 patients were considered for study in four centres in south-west England. Four-hundred-and-fifty patients were randomly allocated to receive care either at home by their family doctor or in hospital, initially in an intensive care unit. The randomised treatment groups were similar in age, history of cardiovascular disease, and incidence of hypotension when first examined. They were followed up for up to a year after onset. The mortality rate at 28 days was 12% for the random home group and 14% for the random hospital group; the corresponding figures at 330 days were 20% and 27%. On average, older patients and those without initial hypotension fared rather better under home care. The patients who underwent randomisation were similar to those whose place of care was not randomised, except that the non-randomised group contained a higher proportion of initially hypotensive patients, whose prognosis was poor wherever treated. These results confirm and extend our preliminary findings. Home care is a proper form of treatment for many patients with acute myocardial infarction, particularly those over 60 years and those with an uncomplicated attack seen by general practitioners."} {"id": "PMID:1268491", "title": "Impaired Lignocaine metabolism in patients with myocardial infarction and cardiac failure.", "content": "Plasma concentrations of lignocaine were measured during and after infusion of lignocaine at 1.4 mg/min for 36-46 hours in 12 patients with myocardial infarction and one patient with cardiac failure due to uncontrolled ventricular tachycardia. In six patients without cardiac failure the plasma concentrations of lignocaine rose progressively during the infusion and the mean lignocaine half life was 4.3 hours compared with 1.4 hours in healthy subjects. Mean plasma lignocaine concentrations were significantly higher in seven patients with cardiac failure, and concentrations also rose during the infusion and the half life was considerably prolonged to 10.2 hours. Lignocaine concentrations rose rapidly to toxic levels when cardiogenic shock developed in one patient and did not fall when the infusion was stopped. The mean plasma antipyrine half life was moderately prolonged (19.4 hours) in a larger group of patients with myocardial infarction and cardiac failure but returned to normal during convalescence (13.2 hours). The metabolism of lignocaine is grossly abnormal in patients with cardiac failure and cardiogenic shock after myocardial infarction.", "contents": "Impaired Lignocaine metabolism in patients with myocardial infarction and cardiac failure. Plasma concentrations of lignocaine were measured during and after infusion of lignocaine at 1.4 mg/min for 36-46 hours in 12 patients with myocardial infarction and one patient with cardiac failure due to uncontrolled ventricular tachycardia. In six patients without cardiac failure the plasma concentrations of lignocaine rose progressively during the infusion and the mean lignocaine half life was 4.3 hours compared with 1.4 hours in healthy subjects. Mean plasma lignocaine concentrations were significantly higher in seven patients with cardiac failure, and concentrations also rose during the infusion and the half life was considerably prolonged to 10.2 hours. Lignocaine concentrations rose rapidly to toxic levels when cardiogenic shock developed in one patient and did not fall when the infusion was stopped. The mean plasma antipyrine half life was moderately prolonged (19.4 hours) in a larger group of patients with myocardial infarction and cardiac failure but returned to normal during convalescence (13.2 hours). The metabolism of lignocaine is grossly abnormal in patients with cardiac failure and cardiogenic shock after myocardial infarction."} {"id": "PMID:1268496", "title": "Nurse specialist in family planning.", "content": "In an experimental clinic, run by nurse specialists in family planning, a total of 768 patients were seen in the first year. Oral contraception was dispensed for 377 patients and 187 intrauterine devices (IUCDs) were inserted; a further 204 IUCD patients attended only for follow-up visits. All side effects were adequately diagnosed by the nurse specialist.", "contents": "Nurse specialist in family planning. In an experimental clinic, run by nurse specialists in family planning, a total of 768 patients were seen in the first year. Oral contraception was dispensed for 377 patients and 187 intrauterine devices (IUCDs) were inserted; a further 204 IUCD patients attended only for follow-up visits. All side effects were adequately diagnosed by the nurse specialist."} {"id": "PMID:1268534", "title": "Prognosis of new and worsening angina pectoris.", "content": "The natural history of new and worsening angina pectoris was studied in 251 men aged under 70 years. Most were ambulant and all were referred by selected general practitioners to a special hospital clinic over two and a half years. Heart attacks developed in 39 patients, nine of whom died. Seventy-two per cent of the attacks occurred within six weeks of the onset or worsening of angina. Of the 212 patients who did not suffer myocardial infarction and who were clinically reviewed six months after their first attendance 66 had been pain free for the previous three months and 14 had experienced only infrequent attacks of angina. Of the 128 men aged under 65 years who were previously in employment 81% had returned to full-time work six months after their first attendance. A discriminant function analysis using many variables was made to develop a predictive index that would allow patients with new or worsening angina who were likely to develop serious cardiac complications to be identified. This did not prove possible, and the only predictive factor of significance was an increased cardiothoracic ratio. The syndrome of new and worsening angina has a low risk of early death, and many patients are symptom free six months later. In general, emergency coronary arteriography and surgery is not indicated.", "contents": "Prognosis of new and worsening angina pectoris. The natural history of new and worsening angina pectoris was studied in 251 men aged under 70 years. Most were ambulant and all were referred by selected general practitioners to a special hospital clinic over two and a half years. Heart attacks developed in 39 patients, nine of whom died. Seventy-two per cent of the attacks occurred within six weeks of the onset or worsening of angina. Of the 212 patients who did not suffer myocardial infarction and who were clinically reviewed six months after their first attendance 66 had been pain free for the previous three months and 14 had experienced only infrequent attacks of angina. Of the 128 men aged under 65 years who were previously in employment 81% had returned to full-time work six months after their first attendance. A discriminant function analysis using many variables was made to develop a predictive index that would allow patients with new or worsening angina who were likely to develop serious cardiac complications to be identified. This did not prove possible, and the only predictive factor of significance was an increased cardiothoracic ratio. The syndrome of new and worsening angina has a low risk of early death, and many patients are symptom free six months later. In general, emergency coronary arteriography and surgery is not indicated."} {"id": "PMID:1268535", "title": "Influence of maternal obesity on subcutaneous fat in the newborn.", "content": "Skinfold thickness measurements were made at biceps, triceps, subscapular, and suprailiac sites on both sides on 265 full-term newborn infants. The mothers were classified as thin (25), normal (179), or obese (61) on the basis of their triceps skinfold thicknesses. At all skinfold sites the babies of the obese mothers were significantly fatter than the babies of normal mothers, and the babies of the normal mothers were significantly fatter than those of the thin mothers. There was a highly significant positive correlation between maternal triceps thickness and the baby's sum of skinfold thicknesses. Hypertension was common during the pregnancies of the obese mothers and was associated with a significant reduction in the babies' skinfold thicknesses. When each of the 61 obese mothers were matched for parity, blood pressure, and smoking habit with 61 non-obese mothers the babies of the obese mothers still had significantly greater skinfold thicknesses than the babies of non-obese mothers.", "contents": "Influence of maternal obesity on subcutaneous fat in the newborn. Skinfold thickness measurements were made at biceps, triceps, subscapular, and suprailiac sites on both sides on 265 full-term newborn infants. The mothers were classified as thin (25), normal (179), or obese (61) on the basis of their triceps skinfold thicknesses. At all skinfold sites the babies of the obese mothers were significantly fatter than the babies of normal mothers, and the babies of the normal mothers were significantly fatter than those of the thin mothers. There was a highly significant positive correlation between maternal triceps thickness and the baby's sum of skinfold thicknesses. Hypertension was common during the pregnancies of the obese mothers and was associated with a significant reduction in the babies' skinfold thicknesses. When each of the 61 obese mothers were matched for parity, blood pressure, and smoking habit with 61 non-obese mothers the babies of the obese mothers still had significantly greater skinfold thicknesses than the babies of non-obese mothers."} {"id": "PMID:1268536", "title": "Comparison of intravenous oxytocin and prostaglandin E2 for accelerating labour.", "content": "In a prospective study of 52 consecutive women who required acceleration of labour intravenous prostaglandin E2 (PGE2) was used as the oxytocic agent. These mothers were matched for age, parity, height, gestational age, initial cervical dilatation, and station and position of the fetal head with 52 women whose labours were accelerated with oxytocin; both drugs were equally effective. Acceleration to delivery intervals, second-stage durations, the number of assisted deliveries, and Apgar scores were similar regardless of the oxytocic used. Although PGE2 compares well with oxytocin, it offers no further advantages and is more expensive and less well tried than oxytocin.", "contents": "Comparison of intravenous oxytocin and prostaglandin E2 for accelerating labour. In a prospective study of 52 consecutive women who required acceleration of labour intravenous prostaglandin E2 (PGE2) was used as the oxytocic agent. These mothers were matched for age, parity, height, gestational age, initial cervical dilatation, and station and position of the fetal head with 52 women whose labours were accelerated with oxytocin; both drugs were equally effective. Acceleration to delivery intervals, second-stage durations, the number of assisted deliveries, and Apgar scores were similar regardless of the oxytocic used. Although PGE2 compares well with oxytocin, it offers no further advantages and is more expensive and less well tried than oxytocin."} {"id": "PMID:1268547", "title": "Plasma nicotine levels after cigarette smoking and chewing nicotine gum.", "content": "Plasma nicotine levels were measured over seven hours of smoking cigarettes (1-2 mg nicotine) in a single subject under standardised conditions, and were compared with the levels obtained from chewing-gum containing either 2 mg or 4 mg nicotine. Levels comparable to those resulting from smoking were not obtained with the 2-mg gum, but peak levels on the 4-mg gum averaged 40-1 ng/ml from the third gum onwards compared with 49-2ng/ml after cigarettes. Nicotine was absorbed much more slowly from the gum than from cigarettes. It took 15-30 minutes for the 4-mg gum to raise the plasma nicotine by an average of 11-9 ng/ml compared with an average increase of 27-8 ng/ml within two minutes of completing each cigarette. In a sample of 15 smokers attending a withdrawal clinic the average plasma nicotine concentration while taking 2-mg nicotine chewing-gum was only 10-8 ng/ml compared with 30-4 ng/ml two minutes after smoking a cigarette. Although plasma nicotine levels equivalent to those following cigarette smoking may be obtained by chewing at least 10 pieces of 4-mg nicotine gum daily, the slower rate of absorption may limit its therapeutic value as a substitute for cigarette smoking.", "contents": "Plasma nicotine levels after cigarette smoking and chewing nicotine gum. Plasma nicotine levels were measured over seven hours of smoking cigarettes (1-2 mg nicotine) in a single subject under standardised conditions, and were compared with the levels obtained from chewing-gum containing either 2 mg or 4 mg nicotine. Levels comparable to those resulting from smoking were not obtained with the 2-mg gum, but peak levels on the 4-mg gum averaged 40-1 ng/ml from the third gum onwards compared with 49-2ng/ml after cigarettes. Nicotine was absorbed much more slowly from the gum than from cigarettes. It took 15-30 minutes for the 4-mg gum to raise the plasma nicotine by an average of 11-9 ng/ml compared with an average increase of 27-8 ng/ml within two minutes of completing each cigarette. In a sample of 15 smokers attending a withdrawal clinic the average plasma nicotine concentration while taking 2-mg nicotine chewing-gum was only 10-8 ng/ml compared with 30-4 ng/ml two minutes after smoking a cigarette. Although plasma nicotine levels equivalent to those following cigarette smoking may be obtained by chewing at least 10 pieces of 4-mg nicotine gum daily, the slower rate of absorption may limit its therapeutic value as a substitute for cigarette smoking."} {"id": "PMID:1268548", "title": "Renal function studies after nephrectomy in renal donors.", "content": "Two to six years after they had donated a kidney the 24-hour creatinine clearances of five women and four men had recovered to 85% and 87% respectively of prenephrectomy performance. The male donors had a lower 24-hour creatinine clearance than age-matched controls, but during dextrose and inulin infusion they had similar values for inulin clearance, creatinine clearance, and glucose reabsorption. By contrast, the female donors had significantly reduced clearances both over 24 hours and during infusion, as well as impaired ability to reabsorb glucose. This suggests that potential female donors should be more vigorously investigated before nephrectomy.", "contents": "Renal function studies after nephrectomy in renal donors. Two to six years after they had donated a kidney the 24-hour creatinine clearances of five women and four men had recovered to 85% and 87% respectively of prenephrectomy performance. The male donors had a lower 24-hour creatinine clearance than age-matched controls, but during dextrose and inulin infusion they had similar values for inulin clearance, creatinine clearance, and glucose reabsorption. By contrast, the female donors had significantly reduced clearances both over 24 hours and during infusion, as well as impaired ability to reabsorb glucose. This suggests that potential female donors should be more vigorously investigated before nephrectomy."} {"id": "PMID:1268549", "title": "Volvulus of the small bowel.", "content": "Over two years in a major hospital in northern Uganda 12 cases of primary volvulus of the small bowel were seen out of a total of 65 cases of intestinal obstruction which did not include external hernias. This relatively high incidence was associated with drinking large amounts of local \"kongo\" beer. General systemic symptoms of circulatory collapse were conspicuous by their absence. The kongo beer was found to have a high concentration of serotonin, and this substance may have caused the volvulus of the small bowel in three quarters of the cases.", "contents": "Volvulus of the small bowel. Over two years in a major hospital in northern Uganda 12 cases of primary volvulus of the small bowel were seen out of a total of 65 cases of intestinal obstruction which did not include external hernias. This relatively high incidence was associated with drinking large amounts of local \"kongo\" beer. General systemic symptoms of circulatory collapse were conspicuous by their absence. The kongo beer was found to have a high concentration of serotonin, and this substance may have caused the volvulus of the small bowel in three quarters of the cases."} {"id": "PMID:1268552", "title": "Undispensed prescriptions in a mining general practice.", "content": "Seven per cent of prescription forms issued in a mining practice were not presented at chemists for dispensing. The people least likely to present their prescription forms were men aged 25-34 years, particularly miners. To get sickness benefit these men have to consult a doctor, but the medical content of the consultation in these circumstances is often perceived by them as irrelevant and the medication rejected. Children and old people nearly always presented their prescriptions. The percentage of undispensed prescription forms for the trainee doctor was higher than for the trainer, but age may have been a factor: older patients tended to consult the established doctor, whom they knew. Drugs affecting the cardiovascular system, moderate or strong analgesics, hypnotics, sedatives, tranquillisers, and antidepressants were rarely rejected, but mild analgesics and drugs prescribed for symptomatic relief, such as those affecting the alimentary system, cough mixtures, and skin preparations, were more often rejected.", "contents": "Undispensed prescriptions in a mining general practice. Seven per cent of prescription forms issued in a mining practice were not presented at chemists for dispensing. The people least likely to present their prescription forms were men aged 25-34 years, particularly miners. To get sickness benefit these men have to consult a doctor, but the medical content of the consultation in these circumstances is often perceived by them as irrelevant and the medication rejected. Children and old people nearly always presented their prescriptions. The percentage of undispensed prescription forms for the trainee doctor was higher than for the trainer, but age may have been a factor: older patients tended to consult the established doctor, whom they knew. Drugs affecting the cardiovascular system, moderate or strong analgesics, hypnotics, sedatives, tranquillisers, and antidepressants were rarely rejected, but mild analgesics and drugs prescribed for symptomatic relief, such as those affecting the alimentary system, cough mixtures, and skin preparations, were more often rejected."} {"id": "PMID:1268584", "title": "Transposition of the great arteries: logical anatomical arterial correction.", "content": "In a 20-month-old child with classic transposition of the great arteries the pulmonary artery, coronary arteries, and aorta were successfully retransposed at arterial level. It was difficult to reimplant the coronary arteries in the dilated pulmonary artery root without damaging the attachments of the valve cusps, and it may be better to divide the pulmonary artery first to avoid this hazard. Retransposition at arterial level will not be suitable for all patients with transposition of the great arteries, and many questions about long-term outcome remain to be answered.", "contents": "Transposition of the great arteries: logical anatomical arterial correction. In a 20-month-old child with classic transposition of the great arteries the pulmonary artery, coronary arteries, and aorta were successfully retransposed at arterial level. It was difficult to reimplant the coronary arteries in the dilated pulmonary artery root without damaging the attachments of the valve cusps, and it may be better to divide the pulmonary artery first to avoid this hazard. Retransposition at arterial level will not be suitable for all patients with transposition of the great arteries, and many questions about long-term outcome remain to be answered."} {"id": "PMID:1268585", "title": "Anatomical correction of complete transposition of the great arteries and ventricular septal defect in infancy.", "content": "Two patients, aged 8 weeks and 5 years, with D transposition of great arteries and large ventricular septal defect were treated by transection of both aorta and pulmonary arteries and reattaching them to the appropriate ventricles. This included the origins of the coronary arteries. The ventricular septal defect was closed through a transverse ventriculotomy using a Dacron patch. The younger child was operated on as an emergency because of cyanosis and severe heart failure resistant to intensive medical treatment. The older child had had previous banding of the pulmonary artery at the age of 1 year. In both patients pulmonary artery pressure dropped to below half systemic pressure immediately after the operation. Postoperative progress was satisfactory with relief of cyanosis and heart failure. Early anatomical correction of transposition of the great arteries and ventricular septal defect is feasible and should play an important part in the management of these patients.", "contents": "Anatomical correction of complete transposition of the great arteries and ventricular septal defect in infancy. Two patients, aged 8 weeks and 5 years, with D transposition of great arteries and large ventricular septal defect were treated by transection of both aorta and pulmonary arteries and reattaching them to the appropriate ventricles. This included the origins of the coronary arteries. The ventricular septal defect was closed through a transverse ventriculotomy using a Dacron patch. The younger child was operated on as an emergency because of cyanosis and severe heart failure resistant to intensive medical treatment. The older child had had previous banding of the pulmonary artery at the age of 1 year. In both patients pulmonary artery pressure dropped to below half systemic pressure immediately after the operation. Postoperative progress was satisfactory with relief of cyanosis and heart failure. Early anatomical correction of transposition of the great arteries and ventricular septal defect is feasible and should play an important part in the management of these patients."} {"id": "PMID:1268586", "title": "Dual-demand pacing for reciprocating atrioventricular tachycardia.", "content": "By using programmed electrical stimulation of the heart and studying the initiation and termination of reciprocating atrioventricular tachycardia two patients with the Wolff-Parkinson-White syndrome were shown to respond rapidly and consistently to fixed-rate pacing. A demand pacemaker was implanted in each patient, having been modified so as to switch into the fixed-rate mode whenever the tachycardia began, thereby terminating the arrhythmia. This appears to be a promising form of treatment in patients with otherwise intractable paroxysmal tachycardia who have been shown by careful study to respond in this way.", "contents": "Dual-demand pacing for reciprocating atrioventricular tachycardia. By using programmed electrical stimulation of the heart and studying the initiation and termination of reciprocating atrioventricular tachycardia two patients with the Wolff-Parkinson-White syndrome were shown to respond rapidly and consistently to fixed-rate pacing. A demand pacemaker was implanted in each patient, having been modified so as to switch into the fixed-rate mode whenever the tachycardia began, thereby terminating the arrhythmia. This appears to be a promising form of treatment in patients with otherwise intractable paroxysmal tachycardia who have been shown by careful study to respond in this way."} {"id": "PMID:1268587", "title": "Value of gallium scanning in seminoma of the testis.", "content": "Whole-body scanning using gallium-67-citrate gave consistently accurate tumour localisation in patients with seminoma of the testis. Thirteen out of 15 scans performed in patients with disseminated seminoma in relapse gave good imaging in all disease areas. Scans in patients with teratoma of the testis were less consistently positive; of nine scans performed in patients with disseminated teratoma seven were entirely negative and two scans lightly imaged large disease masses in two patients. In eight patients with combined (seminoma and teratoma) tumours the scan seemed to reflect the dominant tumour type at the time of scanning. In one of these patients the scans changed from positive to negative, being positive when seminoma was the dominant tumour and negative when a teratoma developed. Gallium-67-citrate scanning is useful in managing seminoma of the testis, both for determining the extent of disease present at initial presentation and for routine follow-up. It may be useful in the differential diagnosis of combined tumours when tumour masses are greater than 2 cm in diameter.", "contents": "Value of gallium scanning in seminoma of the testis. Whole-body scanning using gallium-67-citrate gave consistently accurate tumour localisation in patients with seminoma of the testis. Thirteen out of 15 scans performed in patients with disseminated seminoma in relapse gave good imaging in all disease areas. Scans in patients with teratoma of the testis were less consistently positive; of nine scans performed in patients with disseminated teratoma seven were entirely negative and two scans lightly imaged large disease masses in two patients. In eight patients with combined (seminoma and teratoma) tumours the scan seemed to reflect the dominant tumour type at the time of scanning. In one of these patients the scans changed from positive to negative, being positive when seminoma was the dominant tumour and negative when a teratoma developed. Gallium-67-citrate scanning is useful in managing seminoma of the testis, both for determining the extent of disease present at initial presentation and for routine follow-up. It may be useful in the differential diagnosis of combined tumours when tumour masses are greater than 2 cm in diameter."} {"id": "PMID:1268592", "title": "Community care service for diabetics in the Poole area.", "content": "Because of an increasing work load at the hospital diabetic clinic in Poole general practitioners were asked to help in a community care service for diabetics. In this, general practitioners typically care for non-ketotic patients with maturity onset diabetes who are well controlled on diet or diet and oral hypoglycaemic agents, while the clinic concentrates on more difficult cases and screens patients for long-term complications. The hospital laboratory's work load has been eased because patients may attend for two-hour interval blood sugar estimations when they like; most patients appreciate this flexibility and prefer being looked after by their own doctor. The service has not increased the general practitioners' work load unduly, but it has heightened their awareness of diabetes in the community, thus allowing the diabetic consultant to deal with the problems for which he has been trained. The service has thus provided improved care for all diabetics in the Poole area.", "contents": "Community care service for diabetics in the Poole area. Because of an increasing work load at the hospital diabetic clinic in Poole general practitioners were asked to help in a community care service for diabetics. In this, general practitioners typically care for non-ketotic patients with maturity onset diabetes who are well controlled on diet or diet and oral hypoglycaemic agents, while the clinic concentrates on more difficult cases and screens patients for long-term complications. The hospital laboratory's work load has been eased because patients may attend for two-hour interval blood sugar estimations when they like; most patients appreciate this flexibility and prefer being looked after by their own doctor. The service has not increased the general practitioners' work load unduly, but it has heightened their awareness of diabetes in the community, thus allowing the diabetic consultant to deal with the problems for which he has been trained. The service has thus provided improved care for all diabetics in the Poole area."} {"id": "PMID:1268612", "title": "Unexplained hepatitis following halothane.", "content": "Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur.", "contents": "Unexplained hepatitis following halothane. Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur."} {"id": "PMID:1268613", "title": "Folate-responsive neuropathy: report of 10 cases.", "content": "Ten patients with severe neurological disease that was clinically indistinguishable from subacute combined degeneration of the spinal cord were found to have normal serum vitamin B12 levels. All were folate deficient. Specific folate treatment led to significant reversal of the neuropathy. These findings indicate the need to review orthodox concepts of the role of folic acid in maintaining the integrity of the nervous system.", "contents": "Folate-responsive neuropathy: report of 10 cases. Ten patients with severe neurological disease that was clinically indistinguishable from subacute combined degeneration of the spinal cord were found to have normal serum vitamin B12 levels. All were folate deficient. Specific folate treatment led to significant reversal of the neuropathy. These findings indicate the need to review orthodox concepts of the role of folic acid in maintaining the integrity of the nervous system."} {"id": "PMID:1268614", "title": "Deep venous thrombosis of the legs after strokes. Part I--incidence and predisposing factors.", "content": "Forty out of 76 patients (53%) who had suffered a cerebrovascular accident developed deep venous thrombosis of the paralysed leg, as detected with the 125I-fibrinogen technique. A further five also had thrombosis in the non-paralysed leg. A study of many predisposing risk factors provided no help either in elucidating the cause of venous thromboembolism or in identifying patients at risk of DVT as a complication of cerebrovascular accidents.", "contents": "Deep venous thrombosis of the legs after strokes. Part I--incidence and predisposing factors. Forty out of 76 patients (53%) who had suffered a cerebrovascular accident developed deep venous thrombosis of the paralysed leg, as detected with the 125I-fibrinogen technique. A further five also had thrombosis in the non-paralysed leg. A study of many predisposing risk factors provided no help either in elucidating the cause of venous thromboembolism or in identifying patients at risk of DVT as a complication of cerebrovascular accidents."} {"id": "PMID:1268615", "title": "Deep venous thrombosis of the legs after strokes: Part 2-Natural history.", "content": "Seven out of 76 patients who had sustained a cerebrovascular accident suffered a pulmonary embolism as diagnosed at necropsy or by unequivocal antemortem criteria. A further five patients had probable embolisation diagnosed only by clinical and chest x-ray criteria. Eleven of these 12 patients had DVT as diagnosed by the 125I-fibrinogen technique. Though 125I-fibrinogen technique has its limitations, thrombosis seemed to be able to develop at several independent sites in the venous system of the leg.", "contents": "Deep venous thrombosis of the legs after strokes: Part 2-Natural history. Seven out of 76 patients who had sustained a cerebrovascular accident suffered a pulmonary embolism as diagnosed at necropsy or by unequivocal antemortem criteria. A further five patients had probable embolisation diagnosed only by clinical and chest x-ray criteria. Eleven of these 12 patients had DVT as diagnosed by the 125I-fibrinogen technique. Though 125I-fibrinogen technique has its limitations, thrombosis seemed to be able to develop at several independent sites in the venous system of the leg."} {"id": "PMID:1268616", "title": "Psychiatric morbidity and the menopause: clinical features.", "content": "A sample of 114 women from the general population aged 40-55 years were identified as possible psychiatric cases and subjected to a standardised psychiatric interview. Mean ratings for reported symptoms and observed abnormalities were assessed in relation to menopausal status. There was no evidence of any specific combination of symptoms and signs associated with the cessation of menstrual periods, though after the menopause insomnia and hypochondriacal preoccupations were more common. In comparison with matched normal controls have been previous psychiatric illness, and contact with general practitioners was more frequent. Many women developing psychiatric symptoms at the time of the menopause appear to belong to a vulnerable population who are likely to develop symptoms in relation to stress.", "contents": "Psychiatric morbidity and the menopause: clinical features. A sample of 114 women from the general population aged 40-55 years were identified as possible psychiatric cases and subjected to a standardised psychiatric interview. Mean ratings for reported symptoms and observed abnormalities were assessed in relation to menopausal status. There was no evidence of any specific combination of symptoms and signs associated with the cessation of menstrual periods, though after the menopause insomnia and hypochondriacal preoccupations were more common. In comparison with matched normal controls have been previous psychiatric illness, and contact with general practitioners was more frequent. Many women developing psychiatric symptoms at the time of the menopause appear to belong to a vulnerable population who are likely to develop symptoms in relation to stress."} {"id": "PMID:1268617", "title": "Effects of methyldopa on prolactin and growth hormone.", "content": "The effects of administration of methyldopa on serum prolactin and growth hormone (GH) concentrations in hypertensive patients were studied. Single doses of methyldopa (750 or 1000 mg) significantly increased serum prolactin levels, peak concentrations occurring four to six hours after drug administrations. Long-term methyldopa treatment was associated with threefold to fourfold increases in basal prolactin levels compared with those in normal subjects. In patients treated with methyldopa for two to three weeks the GH response to insulin hypoglycaemia was significantly greater than in normal subjects and untreated hypertensive patients. In contrast, patients treated for prolonged periods (mean 13-4 months) had a GH reponse indistinguishable from normal.", "contents": "Effects of methyldopa on prolactin and growth hormone. The effects of administration of methyldopa on serum prolactin and growth hormone (GH) concentrations in hypertensive patients were studied. Single doses of methyldopa (750 or 1000 mg) significantly increased serum prolactin levels, peak concentrations occurring four to six hours after drug administrations. Long-term methyldopa treatment was associated with threefold to fourfold increases in basal prolactin levels compared with those in normal subjects. In patients treated with methyldopa for two to three weeks the GH response to insulin hypoglycaemia was significantly greater than in normal subjects and untreated hypertensive patients. In contrast, patients treated for prolonged periods (mean 13-4 months) had a GH reponse indistinguishable from normal."} {"id": "PMID:1268625", "title": "Communications to an antenatal clinic.", "content": "When referring pregnant women to an antenatal clinic many general practitioners and midwives presented details of their care in an incomplete and inconsistent manner. As a result, hospital staff often had insufficient basic data from which to work. We recommend that those providing care decide what information they need and make the rationale of collecting this information the subject of a well-evaluated local education programme.", "contents": "Communications to an antenatal clinic. When referring pregnant women to an antenatal clinic many general practitioners and midwives presented details of their care in an incomplete and inconsistent manner. As a result, hospital staff often had insufficient basic data from which to work. We recommend that those providing care decide what information they need and make the rationale of collecting this information the subject of a well-evaluated local education programme."} {"id": "PMID:1268653", "title": "Twenty-four hour monitoring of heart rate and activity in patients with diabetes mellitus: a comparison with clinic investigations.", "content": "Heart rate and activity were recorded continuously in 11 selected diabetics during a normal day, and the observations were compared with results obtained in the same patients in the diabetic outpatient clinic 10 months earlier. Both sets of findings agreed well in heart rate variability and postural tachycardia. In patients with well-controlled diabetes simple tests of reflex cardiovascular control produce results that may be useful in following the course of diabetic autonomic neuropathy.", "contents": "Twenty-four hour monitoring of heart rate and activity in patients with diabetes mellitus: a comparison with clinic investigations. Heart rate and activity were recorded continuously in 11 selected diabetics during a normal day, and the observations were compared with results obtained in the same patients in the diabetic outpatient clinic 10 months earlier. Both sets of findings agreed well in heart rate variability and postural tachycardia. In patients with well-controlled diabetes simple tests of reflex cardiovascular control produce results that may be useful in following the course of diabetic autonomic neuropathy."} {"id": "PMID:1268654", "title": "Beta-cell function improved by supplementing basal insulin secretion in mild diabetes.", "content": "Insulin supplements, predominantly as a constant basal fish insulin infusion, were given to patients with mild diabetes to reduce the overnight fasting glucose level to normal. The basal plasma human insulin levels were reduced to subnormal levels by the infusion, and the insulin response to intravenous glucose was enhanced. The beta-cell in diabetes seems to be in a vicious circle in which an impaired insulin response to glucose produces hyperglycaemia, which stresses beta-cell function, making it more inefficient. A constant basal insulin supplement to induce basal normoglycaemia may benefit beta-cell function in diabetes.", "contents": "Beta-cell function improved by supplementing basal insulin secretion in mild diabetes. Insulin supplements, predominantly as a constant basal fish insulin infusion, were given to patients with mild diabetes to reduce the overnight fasting glucose level to normal. The basal plasma human insulin levels were reduced to subnormal levels by the infusion, and the insulin response to intravenous glucose was enhanced. The beta-cell in diabetes seems to be in a vicious circle in which an impaired insulin response to glucose produces hyperglycaemia, which stresses beta-cell function, making it more inefficient. A constant basal insulin supplement to induce basal normoglycaemia may benefit beta-cell function in diabetes."} {"id": "PMID:1268655", "title": "Effect of triamterene on leucocyte sodium and potassium levels in heart disease.", "content": "Sodium and potassium levels in plasma and leucocytes and the sodium efflux rate constants of leucocytes were measured in patients with congenital heart disease not on treatment, patients with valvular heart disease being treated with digoxin and conventional diuretics, and patients with valvular heart disease receiving digoxin and either conventional diuretics or triamterene or both. The group being treated with digoxin and conventional diuretics showed low cellular potassium levels, low sodium efflux rate constants, and a rise in cellular sodium levels. Patients given triamterene showed a rise in potassium levels in plasma and cells and in the sodium efflux rate constant.", "contents": "Effect of triamterene on leucocyte sodium and potassium levels in heart disease. Sodium and potassium levels in plasma and leucocytes and the sodium efflux rate constants of leucocytes were measured in patients with congenital heart disease not on treatment, patients with valvular heart disease being treated with digoxin and conventional diuretics, and patients with valvular heart disease receiving digoxin and either conventional diuretics or triamterene or both. The group being treated with digoxin and conventional diuretics showed low cellular potassium levels, low sodium efflux rate constants, and a rise in cellular sodium levels. Patients given triamterene showed a rise in potassium levels in plasma and cells and in the sodium efflux rate constant."} {"id": "PMID:1268658", "title": "Why don't we prevent childhood accidents?", "content": "Accidental injury is the most important epidemic in the Western world today, and is especially important as a cause of death and disability in childhood. Many environmental factors are important causes of accidents, but there is no organisation within which doctors, official bodies, industry, and voluntary bodies can pool their experience and co-ordinate their efforts to reduce these environmental risks. A joint committee on childhood accident prevention should be formed in this country similar to that which exists in Sweden.", "contents": "Why don't we prevent childhood accidents? Accidental injury is the most important epidemic in the Western world today, and is especially important as a cause of death and disability in childhood. Many environmental factors are important causes of accidents, but there is no organisation within which doctors, official bodies, industry, and voluntary bodies can pool their experience and co-ordinate their efforts to reduce these environmental risks. A joint committee on childhood accident prevention should be formed in this country similar to that which exists in Sweden."} {"id": "PMID:1268676", "title": "Effects of legal termination on subsequent pregnancy.", "content": "Two hundred and eleven patients who had undergone vaginal termination and were pregnant again were investigated; 43-2% had become pregnant within one year of termination. The overall fetal loss in the 211 patients was 17-5% compared with 7-5% in a group matched for parity but consisting of patients who were pregnant after a spontaneous abortion. Altogether 4-3% of pregnancies after legal abortion ended as first trimester abortions, 8-5% as second trimester abortions, and 13-7% in premature delivery. Among 11 women whose cervices had been lacerated at the time of legal termination the fetal loss in subsequent pregnancy was 45-5%, and only one pregnancy went beyond 36 weeks. Routine Shirodkar suture may be beneficial when the cervix is known to have been damaged at legal abortion. Several patients had asked that their general practitioner should not be told of their termination, and such patients may not admit their termination during a subsequent pregnancy, which could thus be jeopardised. No evidence was found to suggest that infants of patients with a history of legal termination are small for dates.", "contents": "Effects of legal termination on subsequent pregnancy. Two hundred and eleven patients who had undergone vaginal termination and were pregnant again were investigated; 43-2% had become pregnant within one year of termination. The overall fetal loss in the 211 patients was 17-5% compared with 7-5% in a group matched for parity but consisting of patients who were pregnant after a spontaneous abortion. Altogether 4-3% of pregnancies after legal abortion ended as first trimester abortions, 8-5% as second trimester abortions, and 13-7% in premature delivery. Among 11 women whose cervices had been lacerated at the time of legal termination the fetal loss in subsequent pregnancy was 45-5%, and only one pregnancy went beyond 36 weeks. Routine Shirodkar suture may be beneficial when the cervix is known to have been damaged at legal abortion. Several patients had asked that their general practitioner should not be told of their termination, and such patients may not admit their termination during a subsequent pregnancy, which could thus be jeopardised. No evidence was found to suggest that infants of patients with a history of legal termination are small for dates."} {"id": "PMID:1268677", "title": "Fetal activity and fetal wellbeing: an evaluation.", "content": "The clinical value of the 12-hour daily fetal movement count (DFMC) as a test of antepartum fetal wellbeing was assessed. The lowest 2-5% of 1654 DFMCs recorded by 61 women who subsequently delivered healthy infants fell below 10 movements per 12 hours. This level was taken as the lower limit of normal for clinical purposes. A normal DFMC in a population at risk was associated with a satisfactory fetal outcome. A low DFMC was associated with a high incidence of fetal asphyxia, and when fetal death occurred fetal movements rapidly diminished and stopped 12 to 48 hours before death. The DFMC is a generally applicable method of monitoring fetal welfare during pregnancy which provides an inexpensive adjunct or even an alternative to the more expensive placental function tests in current use.", "contents": "Fetal activity and fetal wellbeing: an evaluation. The clinical value of the 12-hour daily fetal movement count (DFMC) as a test of antepartum fetal wellbeing was assessed. The lowest 2-5% of 1654 DFMCs recorded by 61 women who subsequently delivered healthy infants fell below 10 movements per 12 hours. This level was taken as the lower limit of normal for clinical purposes. A normal DFMC in a population at risk was associated with a satisfactory fetal outcome. A low DFMC was associated with a high incidence of fetal asphyxia, and when fetal death occurred fetal movements rapidly diminished and stopped 12 to 48 hours before death. The DFMC is a generally applicable method of monitoring fetal welfare during pregnancy which provides an inexpensive adjunct or even an alternative to the more expensive placental function tests in current use."} {"id": "PMID:1268678", "title": "Standardised approach to gluten challenge in diagnosing childhood coeliac disease.", "content": "Thirty-five children, in whom coeliac disease had been diagnosed on inadequate grounds and who had been on a gluten-free diet for one to 10 years, were challenged with gluten in accordance with a standardised procedure. All children were admitted to hospital for 48 hours for general assessment, two one-hour blood xylose tests, and the introduction of gluten. Thirty children underwent a pre-challenge peroral jejunal mucosal biopsy; the specimens were either normal or showed slight non-specific abnormalities. Gluten powder 20 g/day was given in addition to an otherwise gluten-free diet. The children were reassessed as outpatients every two weeks, when a one-hour blood xylose test was performed. Repeat biopsy was performed when xylose absorption fell or after three months. Seventeen children had abnormal post-challenge biopsy appearances compatible with coeliac disease in relapse; 14 of these children completed their challenge within eight weeks. Seventeen children had completely normal biopsy appearances at the end of three months and were returned to a normal diet. One to two years later eight underwent repeat biopsies, which showed nothing abnormal. In only one child, the oldest in the series, were the histological findings equivocal. In the 17 children in whom coeliac disease was confirmed the duration of gluten challenge was not related to age, duration of gluten-free diet, histological findings on the pre-challenge biopsy, or HLA status.", "contents": "Standardised approach to gluten challenge in diagnosing childhood coeliac disease. Thirty-five children, in whom coeliac disease had been diagnosed on inadequate grounds and who had been on a gluten-free diet for one to 10 years, were challenged with gluten in accordance with a standardised procedure. All children were admitted to hospital for 48 hours for general assessment, two one-hour blood xylose tests, and the introduction of gluten. Thirty children underwent a pre-challenge peroral jejunal mucosal biopsy; the specimens were either normal or showed slight non-specific abnormalities. Gluten powder 20 g/day was given in addition to an otherwise gluten-free diet. The children were reassessed as outpatients every two weeks, when a one-hour blood xylose test was performed. Repeat biopsy was performed when xylose absorption fell or after three months. Seventeen children had abnormal post-challenge biopsy appearances compatible with coeliac disease in relapse; 14 of these children completed their challenge within eight weeks. Seventeen children had completely normal biopsy appearances at the end of three months and were returned to a normal diet. One to two years later eight underwent repeat biopsies, which showed nothing abnormal. In only one child, the oldest in the series, were the histological findings equivocal. In the 17 children in whom coeliac disease was confirmed the duration of gluten challenge was not related to age, duration of gluten-free diet, histological findings on the pre-challenge biopsy, or HLA status."} {"id": "PMID:1268683", "title": "Can geriatrics survive?", "content": "Geriatrics has consistently failed to attract enough staff, and hence geriatric units often cannot provide a full service for the elderly. Meanwhile beds in general medical units may be blocked by elderly patients. This division between geriatric and medical units is arbitrary and wasteful. There are no clinical processes or techniques unique to geriatrics, which is probably why the specialty is unattractive; few doctors want to confine their attention only to the elderly. Geriatrics as a separate specialty should therefore be largely abandoned and the care of the elderly reintegrated into general medicine.", "contents": "Can geriatrics survive? Geriatrics has consistently failed to attract enough staff, and hence geriatric units often cannot provide a full service for the elderly. Meanwhile beds in general medical units may be blocked by elderly patients. This division between geriatric and medical units is arbitrary and wasteful. There are no clinical processes or techniques unique to geriatrics, which is probably why the specialty is unattractive; few doctors want to confine their attention only to the elderly. Geriatrics as a separate specialty should therefore be largely abandoned and the care of the elderly reintegrated into general medicine."} {"id": "PMID:1268691", "title": "Gonorrhoea and foreign immigrants at Rotterdam University Hospital.", "content": "It is estimated, contrary to public opinion and a quick glance at the waiting room of the sexually transmitted diseases (STD) clinic in Rotterdam, that the incidence of gonorrhoea among foreign immigrants is only a little greater than among the Dutch population. The analysis corroborates the common sense idea that the higher incidence of gonorrhoea among foreign immigrants stems largely from their difficulty in finding sexual partners. To solve this problem is a matter of national policy. It is within the scope of the STD clinics and related organizations to start small-scale experiments to improve the difficult medical situation of the foreign immigrants by lowering the linguistic and cultural barriers between the medical staff and their foreign patients. Research on the sexual habits of the patients is of limited value, and a redirection of our efforts seems necessary to tackle this problem.", "contents": "Gonorrhoea and foreign immigrants at Rotterdam University Hospital. It is estimated, contrary to public opinion and a quick glance at the waiting room of the sexually transmitted diseases (STD) clinic in Rotterdam, that the incidence of gonorrhoea among foreign immigrants is only a little greater than among the Dutch population. The analysis corroborates the common sense idea that the higher incidence of gonorrhoea among foreign immigrants stems largely from their difficulty in finding sexual partners. To solve this problem is a matter of national policy. It is within the scope of the STD clinics and related organizations to start small-scale experiments to improve the difficult medical situation of the foreign immigrants by lowering the linguistic and cultural barriers between the medical staff and their foreign patients. Research on the sexual habits of the patients is of limited value, and a redirection of our efforts seems necessary to tackle this problem."} {"id": "PMID:1268700", "title": "Climbing fiber responses of cerebellar Purkinje cells to passive movement of the cat forepaw.", "content": "The activity of cerebellar Purkinje cells during controlled and passive movement of the forepaw was studied in the cat. Burst responses characteristic of activation by climbing fibers were observed in Purkinje cells in lobules Vb and Vc of the cerebellar vermis and paravermis. The climbing fiber responses followed the onset of a movement with a latency ranging from 20 to 60 msec depending upon movement type and amplitude. Responsive Purkinje cells were localized in a well defined parasagittal strip very near the paravermal vein in lobules Vb and Vc. Cells within the responsive strip responded with identical response probabilities and latencies for any particular type of movement presentation. Responses were independent of starting paw position and direction of movement. Climbing fiber responses could be evoked by extremely small movements with most cells responding to displacements of 50 mum. The latencies and probabilities for climbing fiber responses were inversely related to movement amplitude with latencies as long as 80 msec for very small displacements.", "contents": "Climbing fiber responses of cerebellar Purkinje cells to passive movement of the cat forepaw. The activity of cerebellar Purkinje cells during controlled and passive movement of the forepaw was studied in the cat. Burst responses characteristic of activation by climbing fibers were observed in Purkinje cells in lobules Vb and Vc of the cerebellar vermis and paravermis. The climbing fiber responses followed the onset of a movement with a latency ranging from 20 to 60 msec depending upon movement type and amplitude. Responsive Purkinje cells were localized in a well defined parasagittal strip very near the paravermal vein in lobules Vb and Vc. Cells within the responsive strip responded with identical response probabilities and latencies for any particular type of movement presentation. Responses were independent of starting paw position and direction of movement. Climbing fiber responses could be evoked by extremely small movements with most cells responding to displacements of 50 mum. The latencies and probabilities for climbing fiber responses were inversely related to movement amplitude with latencies as long as 80 msec for very small displacements."} {"id": "PMID:1268701", "title": "Nicotinic effect of acetylcholine on the release of newly synthesized (3H)dopamine in rat striatal slices and cat caudate nucleus.", "content": "The effect of acetylcholine (ACh), carbachol and nicotinic blocking agents on the release of newly synthesized [3H]dopamine ([3H]DA) was studied in vitro on rat striatal slices and in vivo on the cat caudate nucleus. In the latter case, the animals were anaesthetized with halothane; in some experimetns an 'enc\u00e9phale isol\u00e9' preparation was used to eliminate anaesthesia. Rat striatal slices placed in a superfusion chamber were continuously superfused with L-[3,5-3H]tyrosine. A cup placed on the ventricular surface of the cat caudate nucleus similarly allowed a continuous superfusion of the structure with the 3H amino acid. In both cases the quantities of [3H]DA contained in serial superfusate fractions were estimated; the drugs were always added in superfusing medium. In vitro ACh (10(-5) M) and carbachol (10(-5) M) enhanced the release of [3H]DA (90%). Similar results were obtained in vivo in anaesthetized cats. The effect of ACh (10(-5) M) was more pronounced (125%) in presence of eserine (10(-4) M) than with ACh alone (65%). ACh was also effective in unanaesthetized cats. The ACh effect on [3H]DA release was reproducible within the same experiment both in vitro and in vivo. This allowed to test the effect of anticholinergic agents on the ACh induced release of [3H]DA. In vivo hexamethonium (10(-4) M, 10(-5) M) partially blocked the release of [3H]DA induced by ACh (10(-5) M) alone; the effect was not seen when ACh was added in the presence of eserine (10(-4) M). Both in vivo and in vitro the prior introduction of mecamylamine into the superfusing medium antagonized the stimulating effect of ACh (10(-5) M) on [3H]DA release. The effects of this nicotinic blocking agent were seen with various concentrations (10(-6); (10(-5) 10(-4) in the in vitro experiments.", "contents": "Nicotinic effect of acetylcholine on the release of newly synthesized (3H)dopamine in rat striatal slices and cat caudate nucleus. The effect of acetylcholine (ACh), carbachol and nicotinic blocking agents on the release of newly synthesized [3H]dopamine ([3H]DA) was studied in vitro on rat striatal slices and in vivo on the cat caudate nucleus. In the latter case, the animals were anaesthetized with halothane; in some experimetns an 'enc\u00e9phale isol\u00e9' preparation was used to eliminate anaesthesia. Rat striatal slices placed in a superfusion chamber were continuously superfused with L-[3,5-3H]tyrosine. A cup placed on the ventricular surface of the cat caudate nucleus similarly allowed a continuous superfusion of the structure with the 3H amino acid. In both cases the quantities of [3H]DA contained in serial superfusate fractions were estimated; the drugs were always added in superfusing medium. In vitro ACh (10(-5) M) and carbachol (10(-5) M) enhanced the release of [3H]DA (90%). Similar results were obtained in vivo in anaesthetized cats. The effect of ACh (10(-5) M) was more pronounced (125%) in presence of eserine (10(-4) M) than with ACh alone (65%). ACh was also effective in unanaesthetized cats. The ACh effect on [3H]DA release was reproducible within the same experiment both in vitro and in vivo. This allowed to test the effect of anticholinergic agents on the ACh induced release of [3H]DA. In vivo hexamethonium (10(-4) M, 10(-5) M) partially blocked the release of [3H]DA induced by ACh (10(-5) M) alone; the effect was not seen when ACh was added in the presence of eserine (10(-4) M). Both in vivo and in vitro the prior introduction of mecamylamine into the superfusing medium antagonized the stimulating effect of ACh (10(-5) M) on [3H]DA release. The effects of this nicotinic blocking agent were seen with various concentrations (10(-6); (10(-5) 10(-4) in the in vitro experiments."} {"id": "PMID:1268702", "title": "Dopaminergic innervation of the rat prefrontal cortex: a fluorescence histochemical study.", "content": "After the destruction of the noradrenergic ascending pathways, the localization of frontal cortical fields receiving fibers from the dopaminergic mesocortical system has been studied in rats, using a glyoxylic-paraformaldehyde method. The dopaminergic innervation was distributed in two main areas. The area of highest density was a medial field which spread in the medial cortex anterior and dorsal to the genu of the corpus callosum. It did not reach the shoulder region except in the foremost part of the frontal lobe where dopaminergic fibers were scattered in the whole cortex, including the molecular layer. A deep sulcal field was situated between the dorsal bank of the rhinal sulcus and the lateral cortex above it. In addition, a moderately dense band of dopaminergic fibers was observed between the corpus callosum and the anterior commissura, beside the accumbens nucleus. Similar data were obtained with dopamine uptake experiments on reserpine-treated but otherwise normal animals. The frontal areas receiving dopaminergic innervation coincide strikingly with the 'prefrontal cortex' as defined by neuroanatomical studies, which is assumed to be more or less equivalent to the prefrontal cortex of primates and derives direct projections from the amygdala. The functional implications of these findings are discussed.", "contents": "Dopaminergic innervation of the rat prefrontal cortex: a fluorescence histochemical study. After the destruction of the noradrenergic ascending pathways, the localization of frontal cortical fields receiving fibers from the dopaminergic mesocortical system has been studied in rats, using a glyoxylic-paraformaldehyde method. The dopaminergic innervation was distributed in two main areas. The area of highest density was a medial field which spread in the medial cortex anterior and dorsal to the genu of the corpus callosum. It did not reach the shoulder region except in the foremost part of the frontal lobe where dopaminergic fibers were scattered in the whole cortex, including the molecular layer. A deep sulcal field was situated between the dorsal bank of the rhinal sulcus and the lateral cortex above it. In addition, a moderately dense band of dopaminergic fibers was observed between the corpus callosum and the anterior commissura, beside the accumbens nucleus. Similar data were obtained with dopamine uptake experiments on reserpine-treated but otherwise normal animals. The frontal areas receiving dopaminergic innervation coincide strikingly with the 'prefrontal cortex' as defined by neuroanatomical studies, which is assumed to be more or less equivalent to the prefrontal cortex of primates and derives direct projections from the amygdala. The functional implications of these findings are discussed."} {"id": "PMID:1268710", "title": "Habituation of exteroceptive suppression and of exteroceptive reflexes in man as influenced by voluntary contraction.", "content": "Habituation kinetics were found to vary considerably in different polysynaptic pathways of the brain stem in man. The exteroceptive reflex of the digastric muscle habituates markedly, even for stimuli repeated at 1-min intervals. The second component of the blink reflex habituates for intervals below about 8 sec, but this can largely be prevented by steady voluntary contraction of the muscle. On the other hand the exteroceptive suppressions of the masseter muscle only disclose slight habitaution of their late component ES2 and no habituation of the early component ES1. This does not appear to be affected by voluntary activation since the suppressive effects present the same pattern in relaxed masseter muscles tested by proprioceptive reflex activation. Exteroceptive reflexes and exteroceptive suppressions of similar latencies disclose genuine and important differences in their habituation kinetics.", "contents": "Habituation of exteroceptive suppression and of exteroceptive reflexes in man as influenced by voluntary contraction. Habituation kinetics were found to vary considerably in different polysynaptic pathways of the brain stem in man. The exteroceptive reflex of the digastric muscle habituates markedly, even for stimuli repeated at 1-min intervals. The second component of the blink reflex habituates for intervals below about 8 sec, but this can largely be prevented by steady voluntary contraction of the muscle. On the other hand the exteroceptive suppressions of the masseter muscle only disclose slight habitaution of their late component ES2 and no habituation of the early component ES1. This does not appear to be affected by voluntary activation since the suppressive effects present the same pattern in relaxed masseter muscles tested by proprioceptive reflex activation. Exteroceptive reflexes and exteroceptive suppressions of similar latencies disclose genuine and important differences in their habituation kinetics."} {"id": "PMID:1268711", "title": "Brain stem and cerebellar lesions in female rats. I. Tests of posture and movement.", "content": "Lesions were placed in a number of brain stem and cerebellar structures to determine their importance to the control of posture and movement in rats. Lesions of the lateral vestibular nucleus, superior vestibular nucleus, or inferior olive produced severe disturbances of posture and movement. Rats with such lesions had pronounced tremor, abnormal head posture and asymmetrical trunk posture, and failed in a balance beam test. Lesions of the medial medullary reticular formation and medial vestibular nucleus had less overall effect on posture and movement, while animals with lesions of the deep cerebellar nuclei were relatively unimpaired. All lesion groups showed some recovery of function during the course of postoperative testing.", "contents": "Brain stem and cerebellar lesions in female rats. I. Tests of posture and movement. Lesions were placed in a number of brain stem and cerebellar structures to determine their importance to the control of posture and movement in rats. Lesions of the lateral vestibular nucleus, superior vestibular nucleus, or inferior olive produced severe disturbances of posture and movement. Rats with such lesions had pronounced tremor, abnormal head posture and asymmetrical trunk posture, and failed in a balance beam test. Lesions of the medial medullary reticular formation and medial vestibular nucleus had less overall effect on posture and movement, while animals with lesions of the deep cerebellar nuclei were relatively unimpaired. All lesion groups showed some recovery of function during the course of postoperative testing."} {"id": "PMID:1268712", "title": "Brain stem and cerebellar lesions in female rats. II. Lordosis reflex.", "content": "The effects of brain stem and cerebellar lesions upon the lordosis reflex were studied. Lesions of the lateral vestibular nucleus (LVN) and nucleus reticularis gigantocellularis (NGc) produced significant deficits in lordosis. Lesions of the deep cerebellar nuclei, inferior olive, medial vestibular nucleus, and superior vestibular nucleus did not produce significant effects. Results from animals with lesions of both lateral vestibular nucleus (LVN) and nucleus gigantocellularis (NGc) suggested that these structures act independently in their control of lordosis. Histological analysis showed that giant cell loss in NGc and Deiters' cell loss in LVN were both significantly correlated with decrements in lordosis. These results indicate that lateral vestibulospinal and reticulospinal pathways participate in the descending control of segmental mechanisms responsible for the lordosis reflex.", "contents": "Brain stem and cerebellar lesions in female rats. II. Lordosis reflex. The effects of brain stem and cerebellar lesions upon the lordosis reflex were studied. Lesions of the lateral vestibular nucleus (LVN) and nucleus reticularis gigantocellularis (NGc) produced significant deficits in lordosis. Lesions of the deep cerebellar nuclei, inferior olive, medial vestibular nucleus, and superior vestibular nucleus did not produce significant effects. Results from animals with lesions of both lateral vestibular nucleus (LVN) and nucleus gigantocellularis (NGc) suggested that these structures act independently in their control of lordosis. Histological analysis showed that giant cell loss in NGc and Deiters' cell loss in LVN were both significantly correlated with decrements in lordosis. These results indicate that lateral vestibulospinal and reticulospinal pathways participate in the descending control of segmental mechanisms responsible for the lordosis reflex."} {"id": "PMID:1268713", "title": "Striate cortex ablation and spatial vision.", "content": "Normal and visually decorticate rats were trained to orient to a luminous target. All subjects reached the same criterion of orientation accuracy, but operated subjects required more training and exhibited greater response latency throughout testing. To determine if visually decorticate subjects located the target according to the retinal position of its image, or only by sampling luminous flux density at different points in space, field-displacing wedge prisms were placed before the subjects' eyes to laterally displace the retinal locus of the target image without affecting luminous flux information. Prism imposition shifted orientation toward the virtual target position for all subjects. In a second study, translucent plastic was place over the subjects' eyes to disrupt the retinal topography and location of the target image while again leaving luminoux flux unaffected as a potential cue. All animals showed a dramatic and complete disruption of target localization once the diffusing material was applied. The data were considered as support for the hypothesis that 'spatial' vision survives visual decortication.", "contents": "Striate cortex ablation and spatial vision. Normal and visually decorticate rats were trained to orient to a luminous target. All subjects reached the same criterion of orientation accuracy, but operated subjects required more training and exhibited greater response latency throughout testing. To determine if visually decorticate subjects located the target according to the retinal position of its image, or only by sampling luminous flux density at different points in space, field-displacing wedge prisms were placed before the subjects' eyes to laterally displace the retinal locus of the target image without affecting luminous flux information. Prism imposition shifted orientation toward the virtual target position for all subjects. In a second study, translucent plastic was place over the subjects' eyes to disrupt the retinal topography and location of the target image while again leaving luminoux flux unaffected as a potential cue. All animals showed a dramatic and complete disruption of target localization once the diffusing material was applied. The data were considered as support for the hypothesis that 'spatial' vision survives visual decortication."} {"id": "PMID:1268714", "title": "A qualitative electron microscopic investigation of the anomalous corticofugal projections following neonatal lesions in the albino rats.", "content": "The present study confirms the suggestive evidence brought forth by the finding of Leong and Lund. Following neonatal lesion of the sensorimotor and adjacent cortex of the albino rats, the remaining intact contralateral cortex projects bilaterally to the superior colliculus, pons and spinal cord, all of which normally receive a unilateral corticofugal projection. Like the normal projections to the 3 areas studied, the anomalous projections form Gray's type I axo-dendritic relations. The terminals of the anomalous projections seem to form a more complex configuration with one axon terminal synapsing on more dendrites than is usual.", "contents": "A qualitative electron microscopic investigation of the anomalous corticofugal projections following neonatal lesions in the albino rats. The present study confirms the suggestive evidence brought forth by the finding of Leong and Lund. Following neonatal lesion of the sensorimotor and adjacent cortex of the albino rats, the remaining intact contralateral cortex projects bilaterally to the superior colliculus, pons and spinal cord, all of which normally receive a unilateral corticofugal projection. Like the normal projections to the 3 areas studied, the anomalous projections form Gray's type I axo-dendritic relations. The terminals of the anomalous projections seem to form a more complex configuration with one axon terminal synapsing on more dendrites than is usual."} {"id": "PMID:1268715", "title": "The distribution of free amino acids in subdivision of rat and frog retinae obtained by a new technique.", "content": "A technique is described for splitting intact rat and frog retinae into laminae. These laminae have been examined histologically and the distribution of free amino acids in the laminae has been determined by the dansylation technique. In both rat and frog retinae, taurine was selectively concentrated in the photoreceptor cells and their processes. In the rat, glycine, glutamine and GABA were especially abundant in a lamina which contained the ganglion, inner plexiform and inner neuronal layers. High concentrations of GABA were also present in the outer plexiform layer. These results are discussed in terms of a possible transmitter function for these amino acids in the retina.", "contents": "The distribution of free amino acids in subdivision of rat and frog retinae obtained by a new technique. A technique is described for splitting intact rat and frog retinae into laminae. These laminae have been examined histologically and the distribution of free amino acids in the laminae has been determined by the dansylation technique. In both rat and frog retinae, taurine was selectively concentrated in the photoreceptor cells and their processes. In the rat, glycine, glutamine and GABA were especially abundant in a lamina which contained the ganglion, inner plexiform and inner neuronal layers. High concentrations of GABA were also present in the outer plexiform layer. These results are discussed in terms of a possible transmitter function for these amino acids in the retina."} {"id": "PMID:1268722", "title": "Temporal sequence of frequency specific and nonspecific effects of flickering lights upon the occipital electrical activity in man.", "content": "Human subjects were exposed 10 times to light flicker for a period of 10 sec, being altered with equal non-flicker periods. Four flicker frequencies were studied: the resting alpha frequency, twice the frequency, and 14 and 6 c/sec, which are both unrelated to alpha rhythms. The effect of flicker stimulation upon the occipital EEG was quantified in terms of integrated values per band over an epoch of 10 sec using a Walter-type frequency analyzer.", "contents": "Temporal sequence of frequency specific and nonspecific effects of flickering lights upon the occipital electrical activity in man. Human subjects were exposed 10 times to light flicker for a period of 10 sec, being altered with equal non-flicker periods. Four flicker frequencies were studied: the resting alpha frequency, twice the frequency, and 14 and 6 c/sec, which are both unrelated to alpha rhythms. The effect of flicker stimulation upon the occipital EEG was quantified in terms of integrated values per band over an epoch of 10 sec using a Walter-type frequency analyzer."} {"id": "PMID:1268723", "title": "The afferent input and functional organization of the hypothalamus in reactions regulating pituitary-adreno-cortical activity.", "content": "In chronic experiments on rabbits, stimulation of the dorsal tegmentum of the midbrain caused an increase in serum corticosteroid level. In acute experiments, stimulation of the same region resulted in changes in the activity of hypothalamic neurons. Neurons in the anterior (AHA), medial (MHA), including the medial dorsal (MHAd) and medial ventral (MHAv) areas, and lateral (LHA) areas of the hypothalamus were studied. When the midbrain was stimulated, more neurons in LHA, MHAd and MHAv were excited than inhibited; in AHA, more neurons were inhibited. These changes suggest that the activation of the pituitary-adrenocortical system caused by stimulation of the dorsal tegmentum is associated with changes in the influx of afferent impulses to the hypothalamus, which are responsible for AHA inhibition and MHA and LHA excitation.", "contents": "The afferent input and functional organization of the hypothalamus in reactions regulating pituitary-adreno-cortical activity. In chronic experiments on rabbits, stimulation of the dorsal tegmentum of the midbrain caused an increase in serum corticosteroid level. In acute experiments, stimulation of the same region resulted in changes in the activity of hypothalamic neurons. Neurons in the anterior (AHA), medial (MHA), including the medial dorsal (MHAd) and medial ventral (MHAv) areas, and lateral (LHA) areas of the hypothalamus were studied. When the midbrain was stimulated, more neurons in LHA, MHAd and MHAv were excited than inhibited; in AHA, more neurons were inhibited. These changes suggest that the activation of the pituitary-adrenocortical system caused by stimulation of the dorsal tegmentum is associated with changes in the influx of afferent impulses to the hypothalamus, which are responsible for AHA inhibition and MHA and LHA excitation."} {"id": "PMID:1268724", "title": "Influences of hypothalamic stimulation upon septal and hippocampal electrical activity in the cat.", "content": "Spontaneous patterns of hippocampal EEG and septal cell activity were studied in immobilized cats, and the influences of high frequency stimulation of medial hypothalamus (MH) and lateral hypothalamus (LH) were determined. Septal cells were divided into 3 classes on the basis of their discharge patterns: (1), rhythmic bursting (2), non-rhythmic bursting and (3), non-bursting, and the relationship of these discharge patterns to hippocampal theta rhythm was analyzed. Rhythmic bursting cells displayed close frequency and phase relations to hippocampal theta rhythm and were located chiefly in the diagonal band of Broca. Cells of the other two categories were found both within and outside of the diagonal band region.", "contents": "Influences of hypothalamic stimulation upon septal and hippocampal electrical activity in the cat. Spontaneous patterns of hippocampal EEG and septal cell activity were studied in immobilized cats, and the influences of high frequency stimulation of medial hypothalamus (MH) and lateral hypothalamus (LH) were determined. Septal cells were divided into 3 classes on the basis of their discharge patterns: (1), rhythmic bursting (2), non-rhythmic bursting and (3), non-bursting, and the relationship of these discharge patterns to hippocampal theta rhythm was analyzed. Rhythmic bursting cells displayed close frequency and phase relations to hippocampal theta rhythm and were located chiefly in the diagonal band of Broca. Cells of the other two categories were found both within and outside of the diagonal band region."} {"id": "PMID:1268725", "title": "Retinofugal projections in the opossum, An anterograde degeneration and radioautographic study.", "content": "A study of anterograde degeneration and anterograde transport was undertaken in the opossum primary optic system in order to clarify several points regarding fiber organization and patterns of terminal fields. Through the radioautographic technique of axon tracing, it was demonstrated that the accessory optic system follows the generalized scheme of Hayhow, consisting of two fascicles the three terminal nuclei.", "contents": "Retinofugal projections in the opossum, An anterograde degeneration and radioautographic study. A study of anterograde degeneration and anterograde transport was undertaken in the opossum primary optic system in order to clarify several points regarding fiber organization and patterns of terminal fields. Through the radioautographic technique of axon tracing, it was demonstrated that the accessory optic system follows the generalized scheme of Hayhow, consisting of two fascicles the three terminal nuclei."} {"id": "PMID:1268726", "title": "Undernutrition in the developing rat: effect upon myelination.", "content": "Long-Evans rats were undernourished from birth by removing the mother from the sucling rats for part of each day; the undernutrition was continued after weaning till 60 days of age by restricting the daily food intake. Brain development was monitored by histologic and selected biochemical analyses coordinated with an ultrastructural morphometric analysis of the pyramidal tract of 30-day-old rats. Brain and body growth were already reduced after 10 days of undernutrition. At 20 days of age, the peak of myelination in the controls, the body and brain weights of the undernourished rats, compared to the controls, were reduced by 25 and 60%, respectively, and by the end of the study (60 days), the brain and body weights were reduced by 30 and 70%, respectively. Morphometric analysis indicated that the proportion of myelinated axons was significantly reduced in starved (34%) relative to control (43%) animals. Fiber analysis revealed that not only were the myelin sheaths thinner in the undernourished rats, but that the sheath was disproportionately reduced relative to the axon diameter. Chemical analysis on a whole brain basis demonstrated a greater than 60% deficit in the relatively myelin-specific galactolipids. (Whole brain analysis included regions more severely affected than the morphometrically analyzed pyramidal tract.) We also obtained evidence for both a delay in the initiation and a general retardation of myelinogenesis. The promyelinating fibers (axons with one or two non-compacted myelin lamellae) still constituted 4.5% of the myelinated fibers in the undernourished animals at 30 days but had declined to 0.3% in the controls. Analysis of the fabtty acids of cerebroside and sulfatide (lipids enriched in myelin) demonstrated in the undernourished group a pattern characteristic of a younger animal. Thus, the effect of undernutrition on the developing rat appears to be one of inhibited and somewhat retarded myelination. These effects were most likely due to a reduction in the number of myelinating glia formed and the restricted capacity of those which form to generate myeline lamellae.", "contents": "Undernutrition in the developing rat: effect upon myelination. Long-Evans rats were undernourished from birth by removing the mother from the sucling rats for part of each day; the undernutrition was continued after weaning till 60 days of age by restricting the daily food intake. Brain development was monitored by histologic and selected biochemical analyses coordinated with an ultrastructural morphometric analysis of the pyramidal tract of 30-day-old rats. Brain and body growth were already reduced after 10 days of undernutrition. At 20 days of age, the peak of myelination in the controls, the body and brain weights of the undernourished rats, compared to the controls, were reduced by 25 and 60%, respectively, and by the end of the study (60 days), the brain and body weights were reduced by 30 and 70%, respectively. Morphometric analysis indicated that the proportion of myelinated axons was significantly reduced in starved (34%) relative to control (43%) animals. Fiber analysis revealed that not only were the myelin sheaths thinner in the undernourished rats, but that the sheath was disproportionately reduced relative to the axon diameter. Chemical analysis on a whole brain basis demonstrated a greater than 60% deficit in the relatively myelin-specific galactolipids. (Whole brain analysis included regions more severely affected than the morphometrically analyzed pyramidal tract.) We also obtained evidence for both a delay in the initiation and a general retardation of myelinogenesis. The promyelinating fibers (axons with one or two non-compacted myelin lamellae) still constituted 4.5% of the myelinated fibers in the undernourished animals at 30 days but had declined to 0.3% in the controls. Analysis of the fabtty acids of cerebroside and sulfatide (lipids enriched in myelin) demonstrated in the undernourished group a pattern characteristic of a younger animal. Thus, the effect of undernutrition on the developing rat appears to be one of inhibited and somewhat retarded myelination. These effects were most likely due to a reduction in the number of myelinating glia formed and the restricted capacity of those which form to generate myeline lamellae."} {"id": "PMID:1268727", "title": "Myelin synthesis during postnatal nutritional deprivation and subsequent rehabilitation.", "content": "Newborn Long-Evans rats were undernourished by maternal deprivation so that by 20 days of age their body and brain weights were about 45 and 80%, respectively, of the values obtained for control (well-nourished) values. Proteins from myelin of undernourished and control rats were separated by polyacrylamide gel electrophoresis in buffers containing sodium dodecyl sulfate. At 15 and 20 days of age the proportion of basic and proteolipid protein was reduced in the starved animals relative to controls, indicative of a delay in maturation. However, by 30 days of age the composition of myelin from starved and control animals appeared similar. At all ages the yield of myelin from brains of starved rats was less than 25% of that obtained from control animals. A series of isotope labeling experiments, using a double label design, was carried out to compare relative rates of incorporation of radioactive amino acids into individual proteins of various brain subcellular fractions. In 20-day-old rats the incorporation of [3H] OR [14C] leucine or glycine into myelin proteins, relative to incorporation into proteins of other subcellular fractions, is preferentially depressed (about 60%) in starved animals. Synthesis of all the myelin proteins was depressed, supporting the hypothesis that the high molecular weight proteins isolated with myelin are true myelin constituents. Similar experiments were conducted using [3H]-and [14C] acetate, choline, or glycerol as precursors of lipids. Incorporation of isotope into lipids of myelin, relative to lipids of other subcellular fractions, was also depressed by about 60% in starved animals. In several experiments we studied synthesis during rehabilitation (ad libitum feeding) following 20 days of postnatal starvation. After 6 days of rehabilitation, incorporation of radioactive precursors into myelin, relative to other subcellular fractions, was still depressed. This result was true for both proteins and lipids, and was interpreted as evicence against the initiation of a process leading to a net recovery of myelin (i.e., an irreversible deficit of myelin synthesis is induced by this regime of nutritional deprivation).", "contents": "Myelin synthesis during postnatal nutritional deprivation and subsequent rehabilitation. Newborn Long-Evans rats were undernourished by maternal deprivation so that by 20 days of age their body and brain weights were about 45 and 80%, respectively, of the values obtained for control (well-nourished) values. Proteins from myelin of undernourished and control rats were separated by polyacrylamide gel electrophoresis in buffers containing sodium dodecyl sulfate. At 15 and 20 days of age the proportion of basic and proteolipid protein was reduced in the starved animals relative to controls, indicative of a delay in maturation. However, by 30 days of age the composition of myelin from starved and control animals appeared similar. At all ages the yield of myelin from brains of starved rats was less than 25% of that obtained from control animals. A series of isotope labeling experiments, using a double label design, was carried out to compare relative rates of incorporation of radioactive amino acids into individual proteins of various brain subcellular fractions. In 20-day-old rats the incorporation of [3H] OR [14C] leucine or glycine into myelin proteins, relative to incorporation into proteins of other subcellular fractions, is preferentially depressed (about 60%) in starved animals. Synthesis of all the myelin proteins was depressed, supporting the hypothesis that the high molecular weight proteins isolated with myelin are true myelin constituents. Similar experiments were conducted using [3H]-and [14C] acetate, choline, or glycerol as precursors of lipids. Incorporation of isotope into lipids of myelin, relative to lipids of other subcellular fractions, was also depressed by about 60% in starved animals. In several experiments we studied synthesis during rehabilitation (ad libitum feeding) following 20 days of postnatal starvation. After 6 days of rehabilitation, incorporation of radioactive precursors into myelin, relative to other subcellular fractions, was still depressed. This result was true for both proteins and lipids, and was interpreted as evicence against the initiation of a process leading to a net recovery of myelin (i.e., an irreversible deficit of myelin synthesis is induced by this regime of nutritional deprivation)."} {"id": "PMID:1268728", "title": "Some properties of the transmitter release mechanism at the rat ganglionic synapse during potassium stimulation.", "content": "In the present investigation a study has been made using intracellular recordings in the rat superior cervical ganglion of the mode of transmitter release induced by raised external potassium ion concentration (40 mM), after acetylcholine synthesis has been blocked by hemicholinium-3. It is shown that the progressive decline in the rate of acetylcholine output from the ganglion is related to a decrease in the number of quanta being released. Furthermore, under these conditions there is no evidence for a reduction in the size of the transmitter quantum. The statistical foundations of the quantal release process at the rat ganglionic synapse have been investigated by comparing the distribution of the number of miniature EPSPs during successive constant time intervals in the tracings with the corresponding Poisson and binomial predictions. Analyses have shown that the probability for a quantum to be released is so small as to produce a binomial distribution of responses indistinquishable fro- the corresponding Poisson distribution, both at the beginning of the potassium-induced quantum discharge and when transmitter release level is low after exhaustion of acetylcholine tissue content.", "contents": "Some properties of the transmitter release mechanism at the rat ganglionic synapse during potassium stimulation. In the present investigation a study has been made using intracellular recordings in the rat superior cervical ganglion of the mode of transmitter release induced by raised external potassium ion concentration (40 mM), after acetylcholine synthesis has been blocked by hemicholinium-3. It is shown that the progressive decline in the rate of acetylcholine output from the ganglion is related to a decrease in the number of quanta being released. Furthermore, under these conditions there is no evidence for a reduction in the size of the transmitter quantum. The statistical foundations of the quantal release process at the rat ganglionic synapse have been investigated by comparing the distribution of the number of miniature EPSPs during successive constant time intervals in the tracings with the corresponding Poisson and binomial predictions. Analyses have shown that the probability for a quantum to be released is so small as to produce a binomial distribution of responses indistinquishable fro- the corresponding Poisson distribution, both at the beginning of the potassium-induced quantum discharge and when transmitter release level is low after exhaustion of acetylcholine tissue content."} {"id": "PMID:1268729", "title": "Topographical distribution of dopaminergic innervation and of dopaminergic receptors in the rat striatum. I. Mictoestimation of [3H] dopamine uptake and dopamine content in microdiscs.", "content": "Topographical variations in the uptake of [3H] dopamine (DA) and in the endogenous content of DA were estimated in the striatum of the rat. For this purpose, microdiscs were punched out in serial 500 mum sections. [3H] DA uptake was measured in 0.25 M sucrose homogenates prepared from microdiscs punched out from frozen slices (--7C). This uptake was similar to that observed in fresh tissues. It was unaffected by desmethylimipramine (5 X 10(-7) M), inhibited by benztropine (10(-6) M) and no longer detectable after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopaminergic pathway. Both [3H] DA uptake and DA content decreased regularly from the rostral to the caudal part of the structure. In contrast, no important differences could be found in the dorso-ventral plane. These results suggest that the extent of dopaminergic innervation is heterogenous within the structure.", "contents": "Topographical distribution of dopaminergic innervation and of dopaminergic receptors in the rat striatum. I. Mictoestimation of [3H] dopamine uptake and dopamine content in microdiscs. Topographical variations in the uptake of [3H] dopamine (DA) and in the endogenous content of DA were estimated in the striatum of the rat. For this purpose, microdiscs were punched out in serial 500 mum sections. [3H] DA uptake was measured in 0.25 M sucrose homogenates prepared from microdiscs punched out from frozen slices (--7C). This uptake was similar to that observed in fresh tissues. It was unaffected by desmethylimipramine (5 X 10(-7) M), inhibited by benztropine (10(-6) M) and no longer detectable after 6-hydroxydopamine-induced degeneration of the nigrostriatal dopaminergic pathway. Both [3H] DA uptake and DA content decreased regularly from the rostral to the caudal part of the structure. In contrast, no important differences could be found in the dorso-ventral plane. These results suggest that the extent of dopaminergic innervation is heterogenous within the structure."} {"id": "PMID:1268730", "title": "Topographical distribution of dopaminergic innervation and of dopaminergic receptors in the rat striatum. II. Distribution and characteristics of dopamine adenylate cyclase--interaction of d-LSD with dopaminergic receptors.", "content": "The characteristics of dopamine adenylate cyclase in the rat striatum were first studied on homogenates of fresh tissues. In the assay conditions used, dopamine (10(-4) M) stimulated the enzyme activity by 250%. This effect was completely blocked by fluphenazine (10(-5) M; Ki=9X10(-9) M) and by phentolamine (10(-5) M; Ki=3 X 10(-7) M). D-LSD stimulated the adenylate cyclase activity (Km=1.4 X 10(-7) M) by interacting with dopamine receptors; indeed the dopamine effect on the enzyme activity was competitively reduced in presence of D-LSD. L-Isoproterenol (Km=10(-6) M) activated an adenylate cyclase through a receptor distinct form the dopaminergic receptor; this stimulation was not affected by fluphenazine or phentolamine but suppressed by DL-propranolol (10(-4) M). The topographical distribution of the dopamine, D-LSD and L-isoproterenol adenylate cyclase activities were examined in homogenates prepared from discs punched out on serial frozed (--7C) slices of the striatum. Under this condition, tge dioanube naxunak stunykatuib was if 150%. A 4.8-fold progressive decrease in the amount of cyclic AMP produced in presence of dopamine (10(-4) M) was observed in the rostrocaudal plane of the structure; the decline of the basal activity was 3.6-fold. The topographical curves of maximal activation of adenylate cyclase by dopamine and D-LSD were superimposable confirming that D-LSD acts on dopaminergic receptors. This topographical distribution of dopamine sensitive adenylate cyclase is comparable on one hand to that of endogenous dopamine and on the other hand to that of the dopamine high affinity uptake activity measured in simultaneous experiments. In contrast to that observed with dopamine or D-LSD, the topographical distribution of the adenylate cyclase sensitive to L-isoproterenol was homogenous within the striatum.", "contents": "Topographical distribution of dopaminergic innervation and of dopaminergic receptors in the rat striatum. II. Distribution and characteristics of dopamine adenylate cyclase--interaction of d-LSD with dopaminergic receptors. The characteristics of dopamine adenylate cyclase in the rat striatum were first studied on homogenates of fresh tissues. In the assay conditions used, dopamine (10(-4) M) stimulated the enzyme activity by 250%. This effect was completely blocked by fluphenazine (10(-5) M; Ki=9X10(-9) M) and by phentolamine (10(-5) M; Ki=3 X 10(-7) M). D-LSD stimulated the adenylate cyclase activity (Km=1.4 X 10(-7) M) by interacting with dopamine receptors; indeed the dopamine effect on the enzyme activity was competitively reduced in presence of D-LSD. L-Isoproterenol (Km=10(-6) M) activated an adenylate cyclase through a receptor distinct form the dopaminergic receptor; this stimulation was not affected by fluphenazine or phentolamine but suppressed by DL-propranolol (10(-4) M). The topographical distribution of the dopamine, D-LSD and L-isoproterenol adenylate cyclase activities were examined in homogenates prepared from discs punched out on serial frozed (--7C) slices of the striatum. Under this condition, tge dioanube naxunak stunykatuib was if 150%. A 4.8-fold progressive decrease in the amount of cyclic AMP produced in presence of dopamine (10(-4) M) was observed in the rostrocaudal plane of the structure; the decline of the basal activity was 3.6-fold. The topographical curves of maximal activation of adenylate cyclase by dopamine and D-LSD were superimposable confirming that D-LSD acts on dopaminergic receptors. This topographical distribution of dopamine sensitive adenylate cyclase is comparable on one hand to that of endogenous dopamine and on the other hand to that of the dopamine high affinity uptake activity measured in simultaneous experiments. In contrast to that observed with dopamine or D-LSD, the topographical distribution of the adenylate cyclase sensitive to L-isoproterenol was homogenous within the striatum."} {"id": "PMID:1268731", "title": "Metal chelates of L-DOPA for improved replenishment of dopaminergic pools.", "content": "An exploratory study consisting of physiochemical and animal experiments was undertaken with the objective of developing one or more metal-L-DOPA chelate systems for an improved transport of L-DOPA into the brain. This approach is based on a theoretical speculation that the pyridoxal-dependent decarboxylation of L-DOPA in the precerebral areas might be obviated by an appropriate metal chelation of the aminocarboxylate end of the L-DOPA molecule. Equilibium studies on the interactions of L-DOPE with Cu2+,Zn2+, Co2+, Mg2+ and Fe2+ ions and their ATP chelates were carried out in order to examine the conditions for the selective binding of the terminal amine group. Metal chelate systems for in vivo transport experiments were selected viz., Cu2+ or Zn2+-L-DOPA (1:2) and Cu2+ or Zn2+-ATP-L-DOPA (1:1:1) which contained the amine-bound metal ion in a completely coordinated form. Results of in vivo studies involving the intraperitoneal administration of 14C-and 3H-LABELED L-DOPA compounds have shown a 100-150% increase in the transport of L-DOPA into the brain by using the Cu2+ and Zn2+ chelates over that effected by using the unchelated L-DOPA. A chromatographic analysis of the brain homogenates showed that only 6% of the overall radioactivity of the brain could be attributed to 3-methoxytyrosine, and the remaining activity was due to DOPA, dopamine and norepinephrine. The transport effectiveness was also compared with that obtained by using the combination drug, RO4-4602 + L-DOPA.", "contents": "Metal chelates of L-DOPA for improved replenishment of dopaminergic pools. An exploratory study consisting of physiochemical and animal experiments was undertaken with the objective of developing one or more metal-L-DOPA chelate systems for an improved transport of L-DOPA into the brain. This approach is based on a theoretical speculation that the pyridoxal-dependent decarboxylation of L-DOPA in the precerebral areas might be obviated by an appropriate metal chelation of the aminocarboxylate end of the L-DOPA molecule. Equilibium studies on the interactions of L-DOPE with Cu2+,Zn2+, Co2+, Mg2+ and Fe2+ ions and their ATP chelates were carried out in order to examine the conditions for the selective binding of the terminal amine group. Metal chelate systems for in vivo transport experiments were selected viz., Cu2+ or Zn2+-L-DOPA (1:2) and Cu2+ or Zn2+-ATP-L-DOPA (1:1:1) which contained the amine-bound metal ion in a completely coordinated form. Results of in vivo studies involving the intraperitoneal administration of 14C-and 3H-LABELED L-DOPA compounds have shown a 100-150% increase in the transport of L-DOPA into the brain by using the Cu2+ and Zn2+ chelates over that effected by using the unchelated L-DOPA. A chromatographic analysis of the brain homogenates showed that only 6% of the overall radioactivity of the brain could be attributed to 3-methoxytyrosine, and the remaining activity was due to DOPA, dopamine and norepinephrine. The transport effectiveness was also compared with that obtained by using the combination drug, RO4-4602 + L-DOPA."} {"id": "PMID:1268739", "title": "Basal forebrain and hypothalamic influences upon brain stem neurons.", "content": "Intracellular recordings were performed from bulbar and caudopontine (BcP), rostropontine (rP) and mesencephalic (Mes) neurons in acute enc\u00e9phale isol\u00e9 preparations during low- and high-frequency basal forebrain (BF) and hypothalamic (Hyp) stimulation. Low-frequency BF stimulation induced long-latency (7-8 msec) EPSPs on 31% of BcP neurons. High-frequency stimulation of the same regions induced excitation in 58% of them. No inhibition was observed. The descending influences on BcP neurons disappeared after bilateral acute sensorimotor decortication. Low- and high-frequency BF stimulation influenced a very low percentage of rP and Mes neurons. The only effect was a long-latency slow rising EPSP with or without spikes. No inhibition was found in these neurons. Low- and high-frequency Hyp stimulation produced short-latency EPSPs with or without spikes on a large percentage of BcP, rP and Mes neurons. The effect was more constant on rostral (rP) than on caudal (BcP) neurons and more evident when high-frequency stimulation was applied. At high frequency the activation of brain stem neurons paralleled an EEG desynchronization. IPSPs were seen in a low percentage of Mes and rP neurons. Mes neurons could be also activated antidromically. The results suggest that BF regions do not antagonize directly the mesencephalic activating system and may induce electrocortical synchronization through the activation of caudal brain stem neurons. This circuit involves sensorimotor cortical neurons. The facilitatory effect of Hyp stimulation on rostral brain stem neurons indicates that the EEG desynchronization which follows high-frequency Hyp activation may be mediated by the ascending reticular system. Other mechanisms mainly at the diencephalo-telecephalic level may however be involved in this effect.", "contents": "Basal forebrain and hypothalamic influences upon brain stem neurons. Intracellular recordings were performed from bulbar and caudopontine (BcP), rostropontine (rP) and mesencephalic (Mes) neurons in acute enc\u00e9phale isol\u00e9 preparations during low- and high-frequency basal forebrain (BF) and hypothalamic (Hyp) stimulation. Low-frequency BF stimulation induced long-latency (7-8 msec) EPSPs on 31% of BcP neurons. High-frequency stimulation of the same regions induced excitation in 58% of them. No inhibition was observed. The descending influences on BcP neurons disappeared after bilateral acute sensorimotor decortication. Low- and high-frequency BF stimulation influenced a very low percentage of rP and Mes neurons. The only effect was a long-latency slow rising EPSP with or without spikes. No inhibition was found in these neurons. Low- and high-frequency Hyp stimulation produced short-latency EPSPs with or without spikes on a large percentage of BcP, rP and Mes neurons. The effect was more constant on rostral (rP) than on caudal (BcP) neurons and more evident when high-frequency stimulation was applied. At high frequency the activation of brain stem neurons paralleled an EEG desynchronization. IPSPs were seen in a low percentage of Mes and rP neurons. Mes neurons could be also activated antidromically. The results suggest that BF regions do not antagonize directly the mesencephalic activating system and may induce electrocortical synchronization through the activation of caudal brain stem neurons. This circuit involves sensorimotor cortical neurons. The facilitatory effect of Hyp stimulation on rostral brain stem neurons indicates that the EEG desynchronization which follows high-frequency Hyp activation may be mediated by the ascending reticular system. Other mechanisms mainly at the diencephalo-telecephalic level may however be involved in this effect."} {"id": "PMID:1268740", "title": "Effects of alpha-toxins from Bungarus multicinctus and Bungarus caeruleus on cholinergic responses in Aplysia neurons.", "content": "The effects of alpha-bungarotoxin from Bungarus multicinctus and Bungarus caeruleus were studied on three types of cholinergic response in Aplysia central neurones. These responses are the result of three distinct changes in ionic permeability: selective increases in permeabiliyt to Na, Cl and K, respectively. It was shown that 10(-5) M alpha-bungarotoxin from B. multicinctus completely blocks the response resulting from an increase in Cl permeability, while having no effect on either of the other two responses types (even when the toxin concentration was increased to 5 X 10(-5) M). The block of the Cl-dependent response by alpha-bungarotoxin is reversible. None of the three response types were affected by similar concentrations of alpha-toxin from B. caeruleus. Higher concentrations were not systematically tested. These results contradict reports of other authors on the action of alpha-bungarotoxin on molluscan acetylcholine (ACh) responses. Possible reasons for the discrepancies between our findings and those published by other authors are discussed.", "contents": "Effects of alpha-toxins from Bungarus multicinctus and Bungarus caeruleus on cholinergic responses in Aplysia neurons. The effects of alpha-bungarotoxin from Bungarus multicinctus and Bungarus caeruleus were studied on three types of cholinergic response in Aplysia central neurones. These responses are the result of three distinct changes in ionic permeability: selective increases in permeabiliyt to Na, Cl and K, respectively. It was shown that 10(-5) M alpha-bungarotoxin from B. multicinctus completely blocks the response resulting from an increase in Cl permeability, while having no effect on either of the other two responses types (even when the toxin concentration was increased to 5 X 10(-5) M). The block of the Cl-dependent response by alpha-bungarotoxin is reversible. None of the three response types were affected by similar concentrations of alpha-toxin from B. caeruleus. Higher concentrations were not systematically tested. These results contradict reports of other authors on the action of alpha-bungarotoxin on molluscan acetylcholine (ACh) responses. Possible reasons for the discrepancies between our findings and those published by other authors are discussed."} {"id": "PMID:1268741", "title": "Selective neuronal accumulation of omega-amino acids in the rabbit retina.", "content": "The uptakes of radioactive glycine, beta-alanine, GABA, delta-aminovaleric acid and epsilon-aminocaproic acid were studied in the rabbit retina in vivo and in vitro. Autoradiography demonstrated that the amino acids were mainly taken up and retained by certain cells of amacrine type. In the neurons, the omega-amino acids seem to be stored in a protected fashion. The uptake of delta-aminovaleric acid and epsilon-aminocaproic acid was temperature dependent, saturable, and of high-affinity type (with Km for delta-aminovaleric acid = 3.02 X 10(-5) M and for epsilon-aminocaproic acid 9.38 X 10(-5) M). The uptake of both delta-aminovaleric acid and epsilon-aminocaproic acid was competitively inhibited by GABA, but not by glycine or a number of other amino acids regarded as possible neurotransmitters. The uptakes of delta-aminolevulinic acid, taurine and alpha-amino-isobutyric acid were studied for comparison, but no selective neuronal uptake was observed. It is concluded that there are certain amacrine cells which selectively accumulate delta-amino acids such as beta-alanine, GABA, delta-aminovaleric acid and epsilon-aminocaproic acid. It seems possible that the mechanism accumulating GABA may also work with the other omega-amino acids. This opens the possibility that the omega-amino acids may serve as 'false neurotransmitters'.", "contents": "Selective neuronal accumulation of omega-amino acids in the rabbit retina. The uptakes of radioactive glycine, beta-alanine, GABA, delta-aminovaleric acid and epsilon-aminocaproic acid were studied in the rabbit retina in vivo and in vitro. Autoradiography demonstrated that the amino acids were mainly taken up and retained by certain cells of amacrine type. In the neurons, the omega-amino acids seem to be stored in a protected fashion. The uptake of delta-aminovaleric acid and epsilon-aminocaproic acid was temperature dependent, saturable, and of high-affinity type (with Km for delta-aminovaleric acid = 3.02 X 10(-5) M and for epsilon-aminocaproic acid 9.38 X 10(-5) M). The uptake of both delta-aminovaleric acid and epsilon-aminocaproic acid was competitively inhibited by GABA, but not by glycine or a number of other amino acids regarded as possible neurotransmitters. The uptakes of delta-aminolevulinic acid, taurine and alpha-amino-isobutyric acid were studied for comparison, but no selective neuronal uptake was observed. It is concluded that there are certain amacrine cells which selectively accumulate delta-amino acids such as beta-alanine, GABA, delta-aminovaleric acid and epsilon-aminocaproic acid. It seems possible that the mechanism accumulating GABA may also work with the other omega-amino acids. This opens the possibility that the omega-amino acids may serve as 'false neurotransmitters'."} {"id": "PMID:1268742", "title": "Decarboxylation of newly formed DOPA by caudate nucleus synaptosomal particles.", "content": "The present study compares dopamine formation from two different sources of DOPA: preformed and added to the medium and that newly formed by the hydroxylations of phenylalanine or tyrosine. Synaptosomal preparations from rat brain caudate nucleus were incubated with 3H-labeled DOPA mixed as cosubstrate with either [14C]phenylalanine or [14C]tyrosine. Following the incubation, DOPA and dopamine were separated and their isotope ratios (isotope in phenylalanine (tyrosine) X 100/isotope in DOPA cosubstrate) were determined and compared. The results show that the ratio in dopamine was not only different from that in DOPA but was in fact 8.3-15.0 times higher. Although the absolute values of the isotope ratios were affected by any changes of the cosubstrate concentrations, the ratio in dopamine was found to be higher than in DOPA at all the substrate concentrations tested. When the synaptosomes were separated post-incubation from the medium and analyzed, the ratio in dopamine was also found to be higher than that in DOPA. Also, the large difference between the intrasynaptosomal ratios persisted throughout the incubation period ranging from 10 to 45 min. The results suggest that the DOPA which is newly formed by the hydroxylations, (a) may not be freely exchangeable with added DOPA because of compartmentation and (b) may be preferentially decarboxylated to dopamine.", "contents": "Decarboxylation of newly formed DOPA by caudate nucleus synaptosomal particles. The present study compares dopamine formation from two different sources of DOPA: preformed and added to the medium and that newly formed by the hydroxylations of phenylalanine or tyrosine. Synaptosomal preparations from rat brain caudate nucleus were incubated with 3H-labeled DOPA mixed as cosubstrate with either [14C]phenylalanine or [14C]tyrosine. Following the incubation, DOPA and dopamine were separated and their isotope ratios (isotope in phenylalanine (tyrosine) X 100/isotope in DOPA cosubstrate) were determined and compared. The results show that the ratio in dopamine was not only different from that in DOPA but was in fact 8.3-15.0 times higher. Although the absolute values of the isotope ratios were affected by any changes of the cosubstrate concentrations, the ratio in dopamine was found to be higher than in DOPA at all the substrate concentrations tested. When the synaptosomes were separated post-incubation from the medium and analyzed, the ratio in dopamine was also found to be higher than that in DOPA. Also, the large difference between the intrasynaptosomal ratios persisted throughout the incubation period ranging from 10 to 45 min. The results suggest that the DOPA which is newly formed by the hydroxylations, (a) may not be freely exchangeable with added DOPA because of compartmentation and (b) may be preferentially decarboxylated to dopamine."} {"id": "PMID:1268755", "title": "Some molecular properties of rat-liver lysosomal beta-glucuronidase isoenzymes.", "content": "The isoenzymes of rat-liver lysosomal beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase (EC 3.2.1.31)) were inactivated at different rates at 0 degrees C in 3M guanidinium chloride solutions adjusted to pH 5.0 In 4 M urea buffered by 0.01 M glycylglycine, pH 7.0 isoenzymes I, III, and V were reversibly inhibited 80%. Sodium dodecyl sulfate (SDS), 0.1% in 0.01 M phosphate buffer, pH 7.0 irreversibly inhibited at 37 degrees C all five isoenzymes. Sedimentation analysis showed that loss of catalytic activity in these denaturing media is accompanied by dissociation into slower sedimenting subunits. SDS gel electrophoresis revealed that the isoenzymes are apparently tetramers made up of different proportions of subunits alpha, beta, and gamma having apparent molecular weights of 62,900, 60,200, and 58,700, respectively. The three subunits appear to be glycoproteins.", "contents": "Some molecular properties of rat-liver lysosomal beta-glucuronidase isoenzymes. The isoenzymes of rat-liver lysosomal beta-glucuronidase (beta-D-glucuronide glucuronosohydrolase (EC 3.2.1.31)) were inactivated at different rates at 0 degrees C in 3M guanidinium chloride solutions adjusted to pH 5.0 In 4 M urea buffered by 0.01 M glycylglycine, pH 7.0 isoenzymes I, III, and V were reversibly inhibited 80%. Sodium dodecyl sulfate (SDS), 0.1% in 0.01 M phosphate buffer, pH 7.0 irreversibly inhibited at 37 degrees C all five isoenzymes. Sedimentation analysis showed that loss of catalytic activity in these denaturing media is accompanied by dissociation into slower sedimenting subunits. SDS gel electrophoresis revealed that the isoenzymes are apparently tetramers made up of different proportions of subunits alpha, beta, and gamma having apparent molecular weights of 62,900, 60,200, and 58,700, respectively. The three subunits appear to be glycoproteins."} {"id": "PMID:1268756", "title": "Studies of the metabolism of asialotransferrins: nonspecific changes in the metabolic behaviour of human asialotransferrin in avians.", "content": "In a previous study (Regoeczi, E. & Hatton, M.W.C. (1976) Can J. Physiol. Pharmacol. 54, 27-34) it was shown that the chicken (Gallus domesticus) does not possess a hepatic asialoglycoprotein receptor. In the present study the same conclusion is drawn for the duck (Anas platyrhynchos). For this reason these avian species were used to assess those changes in the distribution and catabolism of human asialotransferrin which takes place in the absence of the asialoglycoprotein receptor of the liver.", "contents": "Studies of the metabolism of asialotransferrins: nonspecific changes in the metabolic behaviour of human asialotransferrin in avians. In a previous study (Regoeczi, E. & Hatton, M.W.C. (1976) Can J. Physiol. Pharmacol. 54, 27-34) it was shown that the chicken (Gallus domesticus) does not possess a hepatic asialoglycoprotein receptor. In the present study the same conclusion is drawn for the duck (Anas platyrhynchos). For this reason these avian species were used to assess those changes in the distribution and catabolism of human asialotransferrin which takes place in the absence of the asialoglycoprotein receptor of the liver."} {"id": "PMID:1268757", "title": "Relative importance of alternative pathways of purine nucleotide biosynthesis in Ehrlich ascites tumor cells in vivo.", "content": "Several alternative pathways of purine nucleotide synthesis coexist in cells and the relative importance of each pathway for maintaining purine nucleotide concentrations in cells have been studied. Specific inhibitors were used to block these synthetic routes in Ehrlich ascites tumor cells in vivo and the effect of inhibiting each pathway was evaluated by measuring intracellular purine nucleotide concentrations by high-speed liquid chromatography. The results of this study indicate that adenosine triphosphate and guanosine triphosphate concentrations of Ehrlich ascites tumor cells are maintained primarily by purine biosynthesis de novo although other pathways do make significant contributions.", "contents": "Relative importance of alternative pathways of purine nucleotide biosynthesis in Ehrlich ascites tumor cells in vivo. Several alternative pathways of purine nucleotide synthesis coexist in cells and the relative importance of each pathway for maintaining purine nucleotide concentrations in cells have been studied. Specific inhibitors were used to block these synthetic routes in Ehrlich ascites tumor cells in vivo and the effect of inhibiting each pathway was evaluated by measuring intracellular purine nucleotide concentrations by high-speed liquid chromatography. The results of this study indicate that adenosine triphosphate and guanosine triphosphate concentrations of Ehrlich ascites tumor cells are maintained primarily by purine biosynthesis de novo although other pathways do make significant contributions."} {"id": "PMID:1268758", "title": "Acid phosphatases: androgen dependent markers of rat prostate.", "content": "Our investigations on acid phosphatase (AP) were aimed at finding a biochemical assay marker for androgen actions in the rat prostrate. We quantitatively examined the effects of l-tartrate or formaldehyde on AP activity in tissue filtrates from nine adult male rat tissues, plasma and hemolysed red blood cells (HRBC). There was significant inhibition of AP activity in all instances with the exception of HRBC with tartrate. The prostate inhibition results were not different from those for seminal vesicles and adrenals but were different from the other tissues studied. Ten days following castration the inhibition by tartrate was less in all tissues studied except plasma and HRBC; the formaldehyde inhibition percentages were not altered.", "contents": "Acid phosphatases: androgen dependent markers of rat prostate. Our investigations on acid phosphatase (AP) were aimed at finding a biochemical assay marker for androgen actions in the rat prostrate. We quantitatively examined the effects of l-tartrate or formaldehyde on AP activity in tissue filtrates from nine adult male rat tissues, plasma and hemolysed red blood cells (HRBC). There was significant inhibition of AP activity in all instances with the exception of HRBC with tartrate. The prostate inhibition results were not different from those for seminal vesicles and adrenals but were different from the other tissues studied. Ten days following castration the inhibition by tartrate was less in all tissues studied except plasma and HRBC; the formaldehyde inhibition percentages were not altered."} {"id": "PMID:1268763", "title": "The future of sensory aids for the blind.", "content": "Although it is apparent that a successful substitute for vision will not be available for at least two or three decades, the past twenty five years of research is now bearing fruit. Within the next few years several high-technology devices will solve the problems of mobility and reading. Besides this there is a wide range of aids to solve an expanding variety of vocational applications. Great improvements can be expected in the field of closed circuit television and light amplification which will help particularly those with low vision.", "contents": "The future of sensory aids for the blind. Although it is apparent that a successful substitute for vision will not be available for at least two or three decades, the past twenty five years of research is now bearing fruit. Within the next few years several high-technology devices will solve the problems of mobility and reading. Besides this there is a wide range of aids to solve an expanding variety of vocational applications. Great improvements can be expected in the field of closed circuit television and light amplification which will help particularly those with low vision."} {"id": "PMID:1268765", "title": "The location of conduction abnormalities in human entrapment neuropathies.", "content": "Direct stimulation of 23 median, 13 ulnar and 2 peroneal nerves at the time of surgical exploration has been used to locate, and characterize the conduction abnormalities in the nerves. The most frequent location of the major conduction abnormalities in the median nerve was in the first 1-2 cm distal to the origin of the carpal tunnel. In the ulnar nerve the important conduction abnormalities were located most frequently in the segments 1 cm proximal and distal to the medial epicondyle. In the peroneal nerve the major conduction abnormalities occurred proximal or distal to the entry point of the common peroneal nerve into the peroneus longus muscle.", "contents": "The location of conduction abnormalities in human entrapment neuropathies. Direct stimulation of 23 median, 13 ulnar and 2 peroneal nerves at the time of surgical exploration has been used to locate, and characterize the conduction abnormalities in the nerves. The most frequent location of the major conduction abnormalities in the median nerve was in the first 1-2 cm distal to the origin of the carpal tunnel. In the ulnar nerve the important conduction abnormalities were located most frequently in the segments 1 cm proximal and distal to the medial epicondyle. In the peroneal nerve the major conduction abnormalities occurred proximal or distal to the entry point of the common peroneal nerve into the peroneus longus muscle."} {"id": "PMID:1268767", "title": "Classification of aphasic phenomena.", "content": "A brief but comprehensive survey of classifying aphasia reveals that most investigators describe at least four major groups, conveniently labelled Broca's, Wernicke's, anomic and global. Conduction and transcortical aphasias are less generally described and modality specific syndromes rarely, if ever, exist purely. The controversy between unifiers and splitters continues but objective numerical taxonomy may solve some of the problems of classification.", "contents": "Classification of aphasic phenomena. A brief but comprehensive survey of classifying aphasia reveals that most investigators describe at least four major groups, conveniently labelled Broca's, Wernicke's, anomic and global. Conduction and transcortical aphasias are less generally described and modality specific syndromes rarely, if ever, exist purely. The controversy between unifiers and splitters continues but objective numerical taxonomy may solve some of the problems of classification."} {"id": "PMID:1268768", "title": "Integrative versus delay line characteristics of cerebellar cortex.", "content": "In order to determine which of two general models (\"tapped delay line\" or \"integrator\") provides a more accurate desciption of mammalian Purkinje cell (P-cell) activation by natural stimulation, the spatial and temporal characteristics of a population of neurons in cerebellar cortex responsive to small controlled stretches of forelimb muscles were examined in awake, locally anesthetized cats. Stretch of a single wrist muscle excited P-cells over a distance of about 1 mm in the long axis of a folium, a span which is at most half the length of parallel fibers. Both granule cells and molecular layer interneurons were excited over a wider zone than P-cells. Furthermore, P-cells across a response zone all fired on the average at the same time, as determined by computing peristimulus cross-interval histograms from pairs of simultaneously recorded neurons. Consistent delays could only be demonstrated in the minimal response latencies as measured from peristimulus time histograms. These delays, however, were longer than could be ascribed to parallel fiber conduction velocity. No evidence, therefore, was found in cat cerebellum to support the \"tapped delay line\" model, which postulates the successive activation of P-cells as an excitatory volley travels along a parallel fiber beam. Instead, an integrative mode of operation seems to predominate: a relatively wide substratum of activated granule cells simultaneously activates a narrower focus of P-cells centrally situated with respect to the granule cell population. The role of inhibitory interneurons in promoting the \"integrator\" model is discussed.", "contents": "Integrative versus delay line characteristics of cerebellar cortex. In order to determine which of two general models (\"tapped delay line\" or \"integrator\") provides a more accurate desciption of mammalian Purkinje cell (P-cell) activation by natural stimulation, the spatial and temporal characteristics of a population of neurons in cerebellar cortex responsive to small controlled stretches of forelimb muscles were examined in awake, locally anesthetized cats. Stretch of a single wrist muscle excited P-cells over a distance of about 1 mm in the long axis of a folium, a span which is at most half the length of parallel fibers. Both granule cells and molecular layer interneurons were excited over a wider zone than P-cells. Furthermore, P-cells across a response zone all fired on the average at the same time, as determined by computing peristimulus cross-interval histograms from pairs of simultaneously recorded neurons. Consistent delays could only be demonstrated in the minimal response latencies as measured from peristimulus time histograms. These delays, however, were longer than could be ascribed to parallel fiber conduction velocity. No evidence, therefore, was found in cat cerebellum to support the \"tapped delay line\" model, which postulates the successive activation of P-cells as an excitatory volley travels along a parallel fiber beam. Instead, an integrative mode of operation seems to predominate: a relatively wide substratum of activated granule cells simultaneously activates a narrower focus of P-cells centrally situated with respect to the granule cell population. The role of inhibitory interneurons in promoting the \"integrator\" model is discussed."} {"id": "PMID:1268769", "title": "Direct leukocyte migration inhibition in multiple sclerosis--a possible assessment of activity.", "content": "Twenty-four patients with multiple sclerosis were evaluated and classified according to their clinical state. Specific migration inhibition studies were carried out on blood samples from each using myelin basic protein, an acid soluble protein fraction isolated from normal human CNS white matter, and multiple sclerosis myelin basic protein isolated from patients who had the disease, as the antigenic material. This test system employed selected media. Results were compared with those of normal controls and patients with other neurological disease states. Antigen concentration of 500 mu g/ml in serum free medium combined to produce the greatest inhibiting effect on leukocytes in patients with apparent multiple sclerosis and differentiated these patients from those in the other groups tested. Leukocytes in patients who had probable multiple sclerosis with partial impairment, signifying possible current activity of the disease, were especially inhibited as compared to the leukocytes from other groups tested against myelin antigen. Cerebrospinal fluid from affected patients when used as a media enhanced the test. This study suggests that migration inhibition of peripheral leukocytes using myelin protein may be useful in the diagnosis of patients with multiple sclerosis. There is additional evidence that the degree of leukocyte migration inhibition may reflect activity of the disease with its consequent implications on treatment and prognosis.", "contents": "Direct leukocyte migration inhibition in multiple sclerosis--a possible assessment of activity. Twenty-four patients with multiple sclerosis were evaluated and classified according to their clinical state. Specific migration inhibition studies were carried out on blood samples from each using myelin basic protein, an acid soluble protein fraction isolated from normal human CNS white matter, and multiple sclerosis myelin basic protein isolated from patients who had the disease, as the antigenic material. This test system employed selected media. Results were compared with those of normal controls and patients with other neurological disease states. Antigen concentration of 500 mu g/ml in serum free medium combined to produce the greatest inhibiting effect on leukocytes in patients with apparent multiple sclerosis and differentiated these patients from those in the other groups tested. Leukocytes in patients who had probable multiple sclerosis with partial impairment, signifying possible current activity of the disease, were especially inhibited as compared to the leukocytes from other groups tested against myelin antigen. Cerebrospinal fluid from affected patients when used as a media enhanced the test. This study suggests that migration inhibition of peripheral leukocytes using myelin protein may be useful in the diagnosis of patients with multiple sclerosis. There is additional evidence that the degree of leukocyte migration inhibition may reflect activity of the disease with its consequent implications on treatment and prognosis."} {"id": "PMID:1268776", "title": "Clinical and laboratory findings in primary generalized and multiple-myeloma-related amyloidosis.", "content": "Thirty-four patients with primary generalized amyloidosis (PGA) and 14 with multiple-myeloma-related amyloidosis (MRA) were studied. The commonest clinical manifestations in PGA were nephrotic syndrome, hepatomegaly and congestive heart failure, and in MRA, low back pain, plasmacytoma and rheumatoid-arthritis-like syndrome. Eight patients with PGA had limited clinical expression of the disease, such as involvement of only kidneys, joints, parotid glands or gastrointestinal tract; in one patient amyloidosis was limited to lymph nodes. Low serum concentrations of total protein and albumin were common. M components were detected in the serum of 91% of patients with PGA and 92% of patients with MRA: 70% of the M components in PGA and 25% of those in MRA had lambda light chains. Bence Jones proteinemia was detected in 56% of the patients with PGA and in 77% of those with MRA. The serum concentration of immunoglobulins was decreased substantially in more than two thirds of the patients with PGA. Proteinuria (greater than 250 mg/24 h) was observed in 78% of patients with PGA and in 93% of patients with MRA. Bence Jones proteinuria was noted in 75 and 77% of patients, respectively. Plasmacytic infiltration of the bone marrow was found in 90% of the patients with PGA. The mean survival time of the patients with PGA was 28 months and of those with MRA, 29 months from the time of diagnosis.", "contents": "Clinical and laboratory findings in primary generalized and multiple-myeloma-related amyloidosis. Thirty-four patients with primary generalized amyloidosis (PGA) and 14 with multiple-myeloma-related amyloidosis (MRA) were studied. The commonest clinical manifestations in PGA were nephrotic syndrome, hepatomegaly and congestive heart failure, and in MRA, low back pain, plasmacytoma and rheumatoid-arthritis-like syndrome. Eight patients with PGA had limited clinical expression of the disease, such as involvement of only kidneys, joints, parotid glands or gastrointestinal tract; in one patient amyloidosis was limited to lymph nodes. Low serum concentrations of total protein and albumin were common. M components were detected in the serum of 91% of patients with PGA and 92% of patients with MRA: 70% of the M components in PGA and 25% of those in MRA had lambda light chains. Bence Jones proteinemia was detected in 56% of the patients with PGA and in 77% of those with MRA. The serum concentration of immunoglobulins was decreased substantially in more than two thirds of the patients with PGA. Proteinuria (greater than 250 mg/24 h) was observed in 78% of patients with PGA and in 93% of patients with MRA. Bence Jones proteinuria was noted in 75 and 77% of patients, respectively. Plasmacytic infiltration of the bone marrow was found in 90% of the patients with PGA. The mean survival time of the patients with PGA was 28 months and of those with MRA, 29 months from the time of diagnosis."} {"id": "PMID:1268777", "title": "Cryocrystalglobulinemia.", "content": "A 40-year-old woman had cryocrystalglobulinemia with IgG2(K1). To date, 27 other cases of spontaneous crystallization of a plasma protein have been reported. In all, the protein, a cryoglobulin, has been found to be an IgG molecule. The disease most commonly associated with this phenomenon has been multiple myeloma. None of the patients have had Raynaud's phenomenon, but many have had purpuric skin lesions made worse by exposure to cold. In the two cases of essential cryocrystalglobulinemia, crystals were found in the peripheral blood film. Immunologic, biochemical and ultrastructural studies have so far not demonstrated any property common to all cryocrystalglobulins.", "contents": "Cryocrystalglobulinemia. A 40-year-old woman had cryocrystalglobulinemia with IgG2(K1). To date, 27 other cases of spontaneous crystallization of a plasma protein have been reported. In all, the protein, a cryoglobulin, has been found to be an IgG molecule. The disease most commonly associated with this phenomenon has been multiple myeloma. None of the patients have had Raynaud's phenomenon, but many have had purpuric skin lesions made worse by exposure to cold. In the two cases of essential cryocrystalglobulinemia, crystals were found in the peripheral blood film. Immunologic, biochemical and ultrastructural studies have so far not demonstrated any property common to all cryocrystalglobulins."} {"id": "PMID:1268778", "title": "Constipation and catharsis.", "content": "Constipation is endemic in the Western world. Stool consistence and associated symptoms are more important than stool frequency. The patient's attitude towards his bowel habit is also important. Exclusion of \"organic\" disease, reassurance and discussion of normal variations of bowel habit are necessary first steps in treatment. Adquate bulk in the stool must be ensured, either through diet or bulking agnets, and bowel retraining attempted. Laxatives should be reserved for episodes of constipation following enforced bedrest, or as a preparation for diagnostic procedures. Long-term use should be avoided.", "contents": "Constipation and catharsis. Constipation is endemic in the Western world. Stool consistence and associated symptoms are more important than stool frequency. The patient's attitude towards his bowel habit is also important. Exclusion of \"organic\" disease, reassurance and discussion of normal variations of bowel habit are necessary first steps in treatment. Adquate bulk in the stool must be ensured, either through diet or bulking agnets, and bowel retraining attempted. Laxatives should be reserved for episodes of constipation following enforced bedrest, or as a preparation for diagnostic procedures. Long-term use should be avoided."} {"id": "PMID:1268789", "title": "The diabetic day-care unit. II. Comparison of patients and costs of initiating insulin therapy in the unit and a hospital.", "content": "Fifteen patients began insulin treatment in a diabetic day-care unit and 14 patients began insulin treatment in hospital. The cost per patient of initiating insulin treatment in hospital was nine times the cost in a day-care program. In general, the disease of patients with juvenile-onset diabetes was initially under poorer control in those admitted to hospital than in those in the day-care program. However, the day-care juvenile with disease under poorest control was comparable to the most severely affected patient admitted to hospital. No major differences in the improvements in control achieved by the two programs were found.", "contents": "The diabetic day-care unit. II. Comparison of patients and costs of initiating insulin therapy in the unit and a hospital. Fifteen patients began insulin treatment in a diabetic day-care unit and 14 patients began insulin treatment in hospital. The cost per patient of initiating insulin treatment in hospital was nine times the cost in a day-care program. In general, the disease of patients with juvenile-onset diabetes was initially under poorer control in those admitted to hospital than in those in the day-care program. However, the day-care juvenile with disease under poorest control was comparable to the most severely affected patient admitted to hospital. No major differences in the improvements in control achieved by the two programs were found."} {"id": "PMID:1268790", "title": "Juvenile rheumatoid arthritis: follow-up into adulthood - medical, sexual and social status.", "content": "Fifty-eight adults were studied an average of 14.5 years after the diagnosis of juvenile rheumatoid arthritis had been made. The pattern of disease had been typical with respect to various categories, complications and course; HLA-B27 antigen was found at follow-up in 25% of those tested. Two thirds now had mild to moderate disease, good sexual adjustment and \"normal\" educational achievement, employment history and lifestyle. One third had severe disease, often with progressive disability; this did not prevent sexual activity but caused some limitations, and the need for sexual counseling is emphasized. Ongoing activity of the disease process rather than severity of disability seemed the chief factor preventing a normal lifestyle.", "contents": "Juvenile rheumatoid arthritis: follow-up into adulthood - medical, sexual and social status. Fifty-eight adults were studied an average of 14.5 years after the diagnosis of juvenile rheumatoid arthritis had been made. The pattern of disease had been typical with respect to various categories, complications and course; HLA-B27 antigen was found at follow-up in 25% of those tested. Two thirds now had mild to moderate disease, good sexual adjustment and \"normal\" educational achievement, employment history and lifestyle. One third had severe disease, often with progressive disability; this did not prevent sexual activity but caused some limitations, and the need for sexual counseling is emphasized. Ongoing activity of the disease process rather than severity of disability seemed the chief factor preventing a normal lifestyle."} {"id": "PMID:1268791", "title": "Tennis elbow and the cervical spine.", "content": "The exact cause of tennis elbow, a common condition, is still obscure. While the condition may well be entirely due to a local disorder at the elbow, the results of a study of 50 patients whose condition was resistant to 4 weeks of treatment directed to the elbow suggest that the underlying condition may have been (at least in these patients) a reflex localization of pain from radiculopathy at the cervical spine. Clinical, radiologic and electromyographic findings supported this suggestion. The pain was demonstrated to be muscular tenderness, which was maximal and specific at motor points. Treatment directed to the cervical spine appeared to give relief in the majority of patients. The more resistant the condition, the more severe were the radiologic and electromyographic findings in the cervical spine.", "contents": "Tennis elbow and the cervical spine. The exact cause of tennis elbow, a common condition, is still obscure. While the condition may well be entirely due to a local disorder at the elbow, the results of a study of 50 patients whose condition was resistant to 4 weeks of treatment directed to the elbow suggest that the underlying condition may have been (at least in these patients) a reflex localization of pain from radiculopathy at the cervical spine. Clinical, radiologic and electromyographic findings supported this suggestion. The pain was demonstrated to be muscular tenderness, which was maximal and specific at motor points. Treatment directed to the cervical spine appeared to give relief in the majority of patients. The more resistant the condition, the more severe were the radiologic and electromyographic findings in the cervical spine."} {"id": "PMID:1268792", "title": "Lymphoid interstitial pneumonia.", "content": "A 19-year-old man presented with dyspnea, cough and chest pains; he also complained of nausea, anorexia and postprandial vomiting and reported a 10-kg weight loss. Generalized lymphadenopathy and some rales over both lung bases were noted and a chest radiograph showed bilateral nodular lesions. Persistent leukocytosis, thrombocytosis, proteinuria and anergy to a series of natural antigens were found. The diagnosis of lymphoid interstitial pneumonia was made from material obtained at open lung biopsy. Rapid but incomplete clearing of the lung lesions resulted from steroid therapy; the other abnormalities were corrected gradually, except for the proteinuria, which persisted. The clinical improvement and the ability to work and play have been maintained for the past 20 months.", "contents": "Lymphoid interstitial pneumonia. A 19-year-old man presented with dyspnea, cough and chest pains; he also complained of nausea, anorexia and postprandial vomiting and reported a 10-kg weight loss. Generalized lymphadenopathy and some rales over both lung bases were noted and a chest radiograph showed bilateral nodular lesions. Persistent leukocytosis, thrombocytosis, proteinuria and anergy to a series of natural antigens were found. The diagnosis of lymphoid interstitial pneumonia was made from material obtained at open lung biopsy. Rapid but incomplete clearing of the lung lesions resulted from steroid therapy; the other abnormalities were corrected gradually, except for the proteinuria, which persisted. The clinical improvement and the ability to work and play have been maintained for the past 20 months."} {"id": "PMID:1268806", "title": "12-hour psychotherapy.", "content": "The two cases cited illustrate how short-term therapy can be used to meet a patient's needs to deal with loss and grief. Although the goals as set out in short-term therapy contracts are not always fully achieved, this treatment modality, as delineated by Mann, is valuable to psychiatry. Short-term therapy is not only a sound therapeutic intervention, but also a means of bringing psychiatric health care to a greater segment of the population.", "contents": "12-hour psychotherapy. The two cases cited illustrate how short-term therapy can be used to meet a patient's needs to deal with loss and grief. Although the goals as set out in short-term therapy contracts are not always fully achieved, this treatment modality, as delineated by Mann, is valuable to psychiatry. Short-term therapy is not only a sound therapeutic intervention, but also a means of bringing psychiatric health care to a greater segment of the population."} {"id": "PMID:1268817", "title": "Effect of altered lighting regimens, time-limited feeding, and presence of Ehrlich ascites carcinoma on the circadian rhythm in DNA synthesis of mouse spleen.", "content": "The objectives of the series of experiments described were (a) to determine whether there was a circadian rhythm in the incorporation of tritiated thymidine into DNA of the spleen in mice kept on a conventional light-dark cycle and fed ad libitum, (b) to study the effect that different light-dark cycles and a time-limited feeding schedule had on this circadian rhythm, (c) to ascertain what effect the presence of an 8-day Ehrlich ascites carcinoma (EAC) had on the rhythm in DNA synthesis in the spleen and what effect the EAC had on the circadian rhythm in the mitotic index in the corneal epithelium, and (d) to determine whether there was a circadian rhythm in the duration of life-span in mice bearing the EAC. A circadian rhythm in the incorporation of tritiated thymidine into DNA of the mouse spleen consistently was characterized by a peak during the nocturnal phase and a trough during the diurnal phase of the 12-hr light-12-hr dark cycle. In animals bearing an 8-day EAC, the rhythm in DNA synthesis in the spleen was phase-shifted, its wave form was changed, and the overall 24-hr mean was increased significantly. The phasing of the rhythm in EAC-bearing mice was not reproducible. This finding demonstrated that the presence of the EAC severely altered the natural rhythm in DNA synthesis in the spleen and resulted in a rhythmic pattern which was constantly changing. The presence of an 8-day EAC, however, had no effect on the amplitude, overall level, or the phasing of the circadian rhythm in the mitotic index in the cornea. A staggered light-dark cycle of 2 weeks duration did not completely phase-shift the DNA synthesis rhythm in the spleen but did completely phase-shift the rhythm in the mitotic index in the corneal epithelium. In mice subjected to a daily feeding period limited to 4 hr, the rhythm in DNA synthesis in the spleen, in both EAC-bearing and non-EAC bearing mice, was phase-shifted such that the peak occurred during the time of feeding and the trough occurred prior to the feeding period. The rhythm in the mitotic index in the cornea was not phase-shifted or altered in any way by the feeding schedule and thus remained fixed to the light-dark cycle. The DNA synthesis rhythm in the normal spleen demonstrated a phasing very similar to the circadian rhythm in the length of survival in mice challenged with EAC and the circadian rhythm in DNA synthesis in the normal thymus.", "contents": "Effect of altered lighting regimens, time-limited feeding, and presence of Ehrlich ascites carcinoma on the circadian rhythm in DNA synthesis of mouse spleen. The objectives of the series of experiments described were (a) to determine whether there was a circadian rhythm in the incorporation of tritiated thymidine into DNA of the spleen in mice kept on a conventional light-dark cycle and fed ad libitum, (b) to study the effect that different light-dark cycles and a time-limited feeding schedule had on this circadian rhythm, (c) to ascertain what effect the presence of an 8-day Ehrlich ascites carcinoma (EAC) had on the rhythm in DNA synthesis in the spleen and what effect the EAC had on the circadian rhythm in the mitotic index in the corneal epithelium, and (d) to determine whether there was a circadian rhythm in the duration of life-span in mice bearing the EAC. A circadian rhythm in the incorporation of tritiated thymidine into DNA of the mouse spleen consistently was characterized by a peak during the nocturnal phase and a trough during the diurnal phase of the 12-hr light-12-hr dark cycle. In animals bearing an 8-day EAC, the rhythm in DNA synthesis in the spleen was phase-shifted, its wave form was changed, and the overall 24-hr mean was increased significantly. The phasing of the rhythm in EAC-bearing mice was not reproducible. This finding demonstrated that the presence of the EAC severely altered the natural rhythm in DNA synthesis in the spleen and resulted in a rhythmic pattern which was constantly changing. The presence of an 8-day EAC, however, had no effect on the amplitude, overall level, or the phasing of the circadian rhythm in the mitotic index in the cornea. A staggered light-dark cycle of 2 weeks duration did not completely phase-shift the DNA synthesis rhythm in the spleen but did completely phase-shift the rhythm in the mitotic index in the corneal epithelium. In mice subjected to a daily feeding period limited to 4 hr, the rhythm in DNA synthesis in the spleen, in both EAC-bearing and non-EAC bearing mice, was phase-shifted such that the peak occurred during the time of feeding and the trough occurred prior to the feeding period. The rhythm in the mitotic index in the cornea was not phase-shifted or altered in any way by the feeding schedule and thus remained fixed to the light-dark cycle. The DNA synthesis rhythm in the normal spleen demonstrated a phasing very similar to the circadian rhythm in the length of survival in mice challenged with EAC and the circadian rhythm in DNA synthesis in the normal thymus."} {"id": "PMID:1268818", "title": "Enhancing effect of allopurinol on the induction of bladder cancer in rats by n-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.", "content": "The effects of allopurinol on the induction of bladder cancer by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), excretion of urinary tryptophan metabolites, hepatic nitroreductase activity, and the acid-soluble thiol content of liver and blood in weanling female Fischer rats were investigated. Four groups of rats were given normal diet or normal diet supplemented with 0.005% allopurinol, 0.188% FANFT, or 0.005% allopurinol-0.188% FANFT. Transitional cell carcinomas appeared in 3 of 30 rats (10%) at 15 weeks and in 7 of 44 rats (16%) at 20 weeks in the FANFT-treated group; the carcinomas appeared in 14 of 35 rats (40%) at 15 weeks and in 27 of 50 rats (54%) at 20 weeks in the FANFT-allopurinol-treated group. Growth rate was not affected by allopurinol and FANFT. Allopurinol alone caused no morphological change in the epithelial cells of the urinary bladder but decreased hepatic cytosol nitroreductase activity. FANFT alone had no effect on hepatic cytosol or microsomal nitroreductase activity but increased hepatic and blood acid-soluble thiol content. FANFT increased the urinary excretion of anthranilic acid glucuronide, kynurenine, acetylkynurenine, and 3-hydroxykynurenine and decreased indican and o-aminohippurate excretion. Allopurinol did not alter the effects of FANFT on the acid-soluble thiol content of liver and blood or the excretion of urinary tryptophan metabolites.", "contents": "Enhancing effect of allopurinol on the induction of bladder cancer in rats by n-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. The effects of allopurinol on the induction of bladder cancer by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT), excretion of urinary tryptophan metabolites, hepatic nitroreductase activity, and the acid-soluble thiol content of liver and blood in weanling female Fischer rats were investigated. Four groups of rats were given normal diet or normal diet supplemented with 0.005% allopurinol, 0.188% FANFT, or 0.005% allopurinol-0.188% FANFT. Transitional cell carcinomas appeared in 3 of 30 rats (10%) at 15 weeks and in 7 of 44 rats (16%) at 20 weeks in the FANFT-treated group; the carcinomas appeared in 14 of 35 rats (40%) at 15 weeks and in 27 of 50 rats (54%) at 20 weeks in the FANFT-allopurinol-treated group. Growth rate was not affected by allopurinol and FANFT. Allopurinol alone caused no morphological change in the epithelial cells of the urinary bladder but decreased hepatic cytosol nitroreductase activity. FANFT alone had no effect on hepatic cytosol or microsomal nitroreductase activity but increased hepatic and blood acid-soluble thiol content. FANFT increased the urinary excretion of anthranilic acid glucuronide, kynurenine, acetylkynurenine, and 3-hydroxykynurenine and decreased indican and o-aminohippurate excretion. Allopurinol did not alter the effects of FANFT on the acid-soluble thiol content of liver and blood or the excretion of urinary tryptophan metabolites."} {"id": "PMID:1268819", "title": "Cytometric analysis of neoplastic transformation of vertebrate cell populations.", "content": "Two parameters of neoplastic transformation in spontaneously transforming fibroblasts were examined. One parameter, the predilection for rounding of cells at metaphase, was studied using time-lapse cinephotomicrography and fixed, stained preparations. Ten different cell lines were assayed, including established lines of hamster, rat, and mouse cells, and six rodent cultures of known neoplastic potential as determined by animal injection and tumor production. There was a close correlation between the assumption by cells of a spherical shape at metaphase and their ability to form tumors on injection in syngeneic hosts. The projected area of adherent cells 24 hr after plating over a coverglass was used to assay the transition of these rodent cell populations in culture from nonneoplastic to neoplastic. As the cell population became neoplastic, there was a significant decrease in the mean projected area of the cells. Furthermore, as the cell cultures became capable of producing tumors, the projected area profile of the population shifted proportionally to smaller area classes.", "contents": "Cytometric analysis of neoplastic transformation of vertebrate cell populations. Two parameters of neoplastic transformation in spontaneously transforming fibroblasts were examined. One parameter, the predilection for rounding of cells at metaphase, was studied using time-lapse cinephotomicrography and fixed, stained preparations. Ten different cell lines were assayed, including established lines of hamster, rat, and mouse cells, and six rodent cultures of known neoplastic potential as determined by animal injection and tumor production. There was a close correlation between the assumption by cells of a spherical shape at metaphase and their ability to form tumors on injection in syngeneic hosts. The projected area of adherent cells 24 hr after plating over a coverglass was used to assay the transition of these rodent cell populations in culture from nonneoplastic to neoplastic. As the cell population became neoplastic, there was a significant decrease in the mean projected area of the cells. Furthermore, as the cell cultures became capable of producing tumors, the projected area profile of the population shifted proportionally to smaller area classes."} {"id": "PMID:1268820", "title": "Effects of adriamycin on ultrastructure of nucleoli in the heart and liver cells of the rat.", "content": "Ultrastructural studies of the effects of adriamycin on liver and cardiac cell nucleoli of the rat showed that nucleolar segregation occurred within 1 hr after an i.v. injection of a 40-mg/kg dose. Between 3 and 27 hr after this single dose, liver cell nucleoli progressively reverted to a normal ultrastructure. Nucleoli of rat myocardial cells did not recover but underwent further fragmentation, segragation, and conversion to ring-shaped structures. The ultrastructural alterations of myocardial cell nucleoli may represent an important aspect of adriamycin toxicity.", "contents": "Effects of adriamycin on ultrastructure of nucleoli in the heart and liver cells of the rat. Ultrastructural studies of the effects of adriamycin on liver and cardiac cell nucleoli of the rat showed that nucleolar segregation occurred within 1 hr after an i.v. injection of a 40-mg/kg dose. Between 3 and 27 hr after this single dose, liver cell nucleoli progressively reverted to a normal ultrastructure. Nucleoli of rat myocardial cells did not recover but underwent further fragmentation, segragation, and conversion to ring-shaped structures. The ultrastructural alterations of myocardial cell nucleoli may represent an important aspect of adriamycin toxicity."} {"id": "PMID:1268821", "title": "Effects of route and schedule of administration of high-molecular levan on the growth of AKR lymphoma.", "content": "The route and schedule of treatment with high-molecular levan markedly influences its inhibitory effect on the growth of transplanted AKR lymphoma. Injections of levan into the site of the primary tumor were more effective in inhibiting tumor growth and preventing tumor-associated weight loss and mortality than were i.p. injections. Local levan injections inhibited metastatic spread only in mice treated from Days 0 and 2. Levan i.p. was more effective in inhibiting metastases in animals started on treatment 7 to 13 days after tumor inoculation than in animals in which levanization was started earlier. Local injection of levan before inoculation of tumor enhanced tumor growth and shortened life-span in comparison to nonlevanized animals. In mice treated with levan for a short period only, the inhibitory effect on tumor growth slowly vanished within 2 weeks. Some animals treated for 5 to 8 months remained completely free of tumor. The results indicate that the effect of levan on tumor development is mainly topical and depends on the concentration of the polysaccharide in the site. The tumor growth period from 0 to 5 days appears to differ from the following period in the reaction to levan treatment. The nature of this difference is not clear, but possible explanations are discussed.", "contents": "Effects of route and schedule of administration of high-molecular levan on the growth of AKR lymphoma. The route and schedule of treatment with high-molecular levan markedly influences its inhibitory effect on the growth of transplanted AKR lymphoma. Injections of levan into the site of the primary tumor were more effective in inhibiting tumor growth and preventing tumor-associated weight loss and mortality than were i.p. injections. Local levan injections inhibited metastatic spread only in mice treated from Days 0 and 2. Levan i.p. was more effective in inhibiting metastases in animals started on treatment 7 to 13 days after tumor inoculation than in animals in which levanization was started earlier. Local injection of levan before inoculation of tumor enhanced tumor growth and shortened life-span in comparison to nonlevanized animals. In mice treated with levan for a short period only, the inhibitory effect on tumor growth slowly vanished within 2 weeks. Some animals treated for 5 to 8 months remained completely free of tumor. The results indicate that the effect of levan on tumor development is mainly topical and depends on the concentration of the polysaccharide in the site. The tumor growth period from 0 to 5 days appears to differ from the following period in the reaction to levan treatment. The nature of this difference is not clear, but possible explanations are discussed."} {"id": "PMID:1268822", "title": "Tumor induction by a single subcutaneous injection of sterigmatocystin in newborn mice.", "content": "Sterigmatocystin, a mycotoxin produced by Aspergillus versicolor, Aspergillus sydowi, Aspergillus nidulans, and a species of Bipolaris, was given to newborn BALB/c X DBA/2F1 (hereafter referred to as CD2F1) mice by a single s.c. administration in 1% gelatin suspension. In an acute toxicity study, the maximum tolerated dose of sterigmatocystin was 5 mug/g body weight. In a chronic study, a single s.c. injection of 5, 1, or 0.5 mug/g body weight gave rise to high incidences of lung and liver adenomas when the animals were killed at the end of 1 year. The incidence of both tumors in mice at the dose of 5 mug/g body weight was statistically significant, and the incidences of lung tumor in female mice and of liver tumor in male mice at the dose of 1 mug/g body weight were also statistically significant, compared with tumors in control mice. Other tumors also were induced in treated mice (two malignant lymphomas and one adenoma of the submaxillary gland), in contrast to a zero incidence in vehicle control mice. These results confirm that a small quantity of sterigmatocystin induces tumors of lung and liver and that the dose of sterigmatocystin is related to the incidence of tumors in mice.", "contents": "Tumor induction by a single subcutaneous injection of sterigmatocystin in newborn mice. Sterigmatocystin, a mycotoxin produced by Aspergillus versicolor, Aspergillus sydowi, Aspergillus nidulans, and a species of Bipolaris, was given to newborn BALB/c X DBA/2F1 (hereafter referred to as CD2F1) mice by a single s.c. administration in 1% gelatin suspension. In an acute toxicity study, the maximum tolerated dose of sterigmatocystin was 5 mug/g body weight. In a chronic study, a single s.c. injection of 5, 1, or 0.5 mug/g body weight gave rise to high incidences of lung and liver adenomas when the animals were killed at the end of 1 year. The incidence of both tumors in mice at the dose of 5 mug/g body weight was statistically significant, and the incidences of lung tumor in female mice and of liver tumor in male mice at the dose of 1 mug/g body weight were also statistically significant, compared with tumors in control mice. Other tumors also were induced in treated mice (two malignant lymphomas and one adenoma of the submaxillary gland), in contrast to a zero incidence in vehicle control mice. These results confirm that a small quantity of sterigmatocystin induces tumors of lung and liver and that the dose of sterigmatocystin is related to the incidence of tumors in mice."} {"id": "PMID:1268823", "title": "Vasoformative sarcomas arising from BALB/3T3 cells attached to solid substrates.", "content": "The BALB/3T3 mouse embryo cell line, noted for its marked postconfluence inhibition of proliferation, anchorage dependence, and high serum requirement, and frequently studied as a prototype nontumorigenic \"fibroblast\" line that is compared with tumorigenic sublines transformed with various agents, produced tumors within 2 to 3 months when an average of 3 X 10(4) cells were implanted s.c. attached to 1- X 5- X 10-mm polycarbonate platelets. Plastic platelets alone produced no tumors after 1 year of observation. The tumors, as well as others arising from implants of BALB/3T3 cells attached to 3-mm glass beads, were given the histological diagnosis of \"vasoformative saroma\" because the tumor cells frequently formed vascular channels. The vasoformative pattern and the results of specific staining for reticulin and collagen support the likelihood that BALB/3T3 cells originated from endothelial cells rather than from fibroblasts. That the tumors were derived from BALB/3T3 cells and not host cells was proved when tumors arising in BALB/c X C57BL/6 F1 hybrids were shown to be transplantable to BALB/c but not to C57BL/6 mice. The cultured tumor cells showed loss of both postconfluence inhibition of proliferation and anchorage dependence. Evidence of the induction of endogenous oncornaviruses was obtained in only one of four tumors tested. These tumors also exhibited tumor-unique transplantation rejection antigens. We conclude that BALB/3T3 cells are preneoplastic and give rise to different spontaneously transformed clones bearing unique tumor rejection antigens when implanted in vivo attached to a solid substrate.", "contents": "Vasoformative sarcomas arising from BALB/3T3 cells attached to solid substrates. The BALB/3T3 mouse embryo cell line, noted for its marked postconfluence inhibition of proliferation, anchorage dependence, and high serum requirement, and frequently studied as a prototype nontumorigenic \"fibroblast\" line that is compared with tumorigenic sublines transformed with various agents, produced tumors within 2 to 3 months when an average of 3 X 10(4) cells were implanted s.c. attached to 1- X 5- X 10-mm polycarbonate platelets. Plastic platelets alone produced no tumors after 1 year of observation. The tumors, as well as others arising from implants of BALB/3T3 cells attached to 3-mm glass beads, were given the histological diagnosis of \"vasoformative saroma\" because the tumor cells frequently formed vascular channels. The vasoformative pattern and the results of specific staining for reticulin and collagen support the likelihood that BALB/3T3 cells originated from endothelial cells rather than from fibroblasts. That the tumors were derived from BALB/3T3 cells and not host cells was proved when tumors arising in BALB/c X C57BL/6 F1 hybrids were shown to be transplantable to BALB/c but not to C57BL/6 mice. The cultured tumor cells showed loss of both postconfluence inhibition of proliferation and anchorage dependence. Evidence of the induction of endogenous oncornaviruses was obtained in only one of four tumors tested. These tumors also exhibited tumor-unique transplantation rejection antigens. We conclude that BALB/3T3 cells are preneoplastic and give rise to different spontaneously transformed clones bearing unique tumor rejection antigens when implanted in vivo attached to a solid substrate."} {"id": "PMID:1268824", "title": "Modification of the response to actinomycin D-induced sublethal damage by simultaneous recovery from potentially lethal damage in mammalian cells.", "content": "Exponentially growing cells and cells that were allowed to enter a plateau or nondividing state of growth by depleting the medium of growth-essential nutrients were used in these studies. Nondividing Chinese hamster ovary cells in vitro are less sensitive to actinomycin D (AMD) than are exponentially growing cells. The cells were tested for their ability to recover from AMD-induced potentially lethal damage (PLD) or sublethal damage. The proliferating and the nonproliferating cells do not recover from PLD or sublethal damage, and they experience further reductions in survival when they are maintained under the medium conditions of their respective growth states. However, when dividing cells are placed in conditions suboptimal for growth (incubated in depleted plateau medium after treatment with AMD), they did exhibit increased survival. The PLD recovery was so great under these conditions that it masked the true response of the cells to fractionated doses of AMD. When adjustments were made for the PLD recovery, the resulting data indicated a slight but measurable increase in survival. Since AMD inhibits cell progression in all stages of the cell cycle, this increase in survival observed with fractionated doses of AMD may be due to true recovery from sublethal damage, although the movement of cells into less sensitive stages of the cell cycle between treatments cannot be ruled out.", "contents": "Modification of the response to actinomycin D-induced sublethal damage by simultaneous recovery from potentially lethal damage in mammalian cells. Exponentially growing cells and cells that were allowed to enter a plateau or nondividing state of growth by depleting the medium of growth-essential nutrients were used in these studies. Nondividing Chinese hamster ovary cells in vitro are less sensitive to actinomycin D (AMD) than are exponentially growing cells. The cells were tested for their ability to recover from AMD-induced potentially lethal damage (PLD) or sublethal damage. The proliferating and the nonproliferating cells do not recover from PLD or sublethal damage, and they experience further reductions in survival when they are maintained under the medium conditions of their respective growth states. However, when dividing cells are placed in conditions suboptimal for growth (incubated in depleted plateau medium after treatment with AMD), they did exhibit increased survival. The PLD recovery was so great under these conditions that it masked the true response of the cells to fractionated doses of AMD. When adjustments were made for the PLD recovery, the resulting data indicated a slight but measurable increase in survival. Since AMD inhibits cell progression in all stages of the cell cycle, this increase in survival observed with fractionated doses of AMD may be due to true recovery from sublethal damage, although the movement of cells into less sensitive stages of the cell cycle between treatments cannot be ruled out."} {"id": "PMID:1268825", "title": "Immune response of BALB/c X DBA/2F1 mice to a tumor allograft during pyran copolymer-induced tumor enhancement.", "content": "The immune response of BALB/c x DBA/2 F1 mice to a transplantable Moloney leukemia virus-induced tumor allograft (MBL-2) was studied to determine the mechanism of pyran copolymer-induced tumor enhancement. The relative levels of humoral, lymphocyte, and macrophage response were followed chronologically by in vitro cytotoxic microassays using 51Cr-labeled target cells. Although pyran increased the titer of humoral cytotoxic antibody, levels of humoral factors capable of abrogating lymphocytoxicity were not enhanced. Furthermore, splenic lymphocyte-mediated cytotoxicity, although slightly diminished in pyran-treated mice, was not significantly affected. Macrophages harvested from allograft-bearing animals exhibited marked tumoricidal activity, which was augmented by pyran treatment. This macrophage-associated activity was specific for MBL-2 cells and not attributable to cytotoxins elaborated into the culture medium. Pyran slightly activated macrophages from nonsensitized mice to become cytotoxic for MBL-2 cells; activation was not T-cell dependent. However, strikingly fewer macrophages infiltrated the allograft in pyran-treated animals as judged by both histopathology and direct measurement. The defect in the migration or deposit of macrophages at the allograft site may have contributed to tumor enhancement.", "contents": "Immune response of BALB/c X DBA/2F1 mice to a tumor allograft during pyran copolymer-induced tumor enhancement. The immune response of BALB/c x DBA/2 F1 mice to a transplantable Moloney leukemia virus-induced tumor allograft (MBL-2) was studied to determine the mechanism of pyran copolymer-induced tumor enhancement. The relative levels of humoral, lymphocyte, and macrophage response were followed chronologically by in vitro cytotoxic microassays using 51Cr-labeled target cells. Although pyran increased the titer of humoral cytotoxic antibody, levels of humoral factors capable of abrogating lymphocytoxicity were not enhanced. Furthermore, splenic lymphocyte-mediated cytotoxicity, although slightly diminished in pyran-treated mice, was not significantly affected. Macrophages harvested from allograft-bearing animals exhibited marked tumoricidal activity, which was augmented by pyran treatment. This macrophage-associated activity was specific for MBL-2 cells and not attributable to cytotoxins elaborated into the culture medium. Pyran slightly activated macrophages from nonsensitized mice to become cytotoxic for MBL-2 cells; activation was not T-cell dependent. However, strikingly fewer macrophages infiltrated the allograft in pyran-treated animals as judged by both histopathology and direct measurement. The defect in the migration or deposit of macrophages at the allograft site may have contributed to tumor enhancement."} {"id": "PMID:1268826", "title": "Kinetic alterations induced by 5-fluorouracil in bone marrow, intestinal mucosa, and tumor.", "content": "In order to provide a more rational approach to the design of chemotherapeutic programs involving 5-fluorouracil (5-FU), the kinetic effect of this drug on bone marrow, gastrointestinal epithelium, and tumorous tissues in mice was monitored by determining the rate of incorporation of labeled deoxyuridine (UdR) into DNA following doses of 15, 50, and 100 mg/kg i.p: In BALB/c x DBA/2 F1 (hereafter called CD2F1) mice bearing P1534 ascites tumor, the magnitude and duration of suppression of [3H]UdR incorporation into DNA were directly related to drug dose for both the normal and tumorous tissues. However, the impact of 5-FU was clearly greater upon the P1534 ascites tumor than on either normal tissue, so that, after a dose of 100 mg/kg, the tumor did not initiate recovery until Day 5, while duodenal mucosa and bone marrow returned to 50% of control levels of UdR incorporation at 2 and 3 days, respectively. In order to determine whether the duration of suppression of [3H]UdR incorporation, such as observed in the P1534 ascites tumor, correlated with sensitivity of Ehrlich ascites tumor to 5-FU, the effect of 50 and 100 mg/kg of 5-FU i.p. on this less 5-FU-sensitive tumor was determined. No difference was observed in the time course of suppression and recovery between Ehrlich ascites tumor and the duodenal mucosa and bone marrow of the G.P. Swiss host. In non-tumor-bearing CD2F1 mice, the toxicity of a 2nd dose of 100 mg/kg 5-FU i.p. was found to be predictably related to the kinetic effect of a 1st dose of 100 mg/kg on [3H]UdR incorporation in the bone marrow and duodenal mucosa. In the time period from 12 hr through Day 6, when [3H]UdR incorporation into DNA rose to a maximum, administration of a 2nd dose of 5-FU was associated with 95% lethality. In contrast, during the period between 0 and 12 hr that preceded recovery of UdR incorporation, a 2nd dose resulted in less than 40% lethality, and, in the period from Day 6 through Day 8, when UdR incorporation was declining, lethality of a 2nd dose also declined to less than 25% lethality. In addition, the antitumor effectiveness of a 2nd dose of 5-FU, 100 mg/kg i.p., was predictably related to the differential effect of the 1st dose of 100 mg/kg on [3H]UdR incorporation in the P1534 tumor as compared to the host bone marrow and duodenal mucosa. Administration of a 2nd dose of 5-FU was maximally effective on Day 7, at a time when [3H]UdR incorporation was declining in the host target tissues and increasing to a maximum in the P1534 ascites tumor. Thus, the present study has demonstrated that [3H]UdR incorporation into DNA may be used to monitor the differential effect of 5-FU on tumor versus normal proliferating host tissues and, where such differences exist, to provide an in vivo method of value in designing a schedule of optimum therapeutic benefit.", "contents": "Kinetic alterations induced by 5-fluorouracil in bone marrow, intestinal mucosa, and tumor. In order to provide a more rational approach to the design of chemotherapeutic programs involving 5-fluorouracil (5-FU), the kinetic effect of this drug on bone marrow, gastrointestinal epithelium, and tumorous tissues in mice was monitored by determining the rate of incorporation of labeled deoxyuridine (UdR) into DNA following doses of 15, 50, and 100 mg/kg i.p: In BALB/c x DBA/2 F1 (hereafter called CD2F1) mice bearing P1534 ascites tumor, the magnitude and duration of suppression of [3H]UdR incorporation into DNA were directly related to drug dose for both the normal and tumorous tissues. However, the impact of 5-FU was clearly greater upon the P1534 ascites tumor than on either normal tissue, so that, after a dose of 100 mg/kg, the tumor did not initiate recovery until Day 5, while duodenal mucosa and bone marrow returned to 50% of control levels of UdR incorporation at 2 and 3 days, respectively. In order to determine whether the duration of suppression of [3H]UdR incorporation, such as observed in the P1534 ascites tumor, correlated with sensitivity of Ehrlich ascites tumor to 5-FU, the effect of 50 and 100 mg/kg of 5-FU i.p. on this less 5-FU-sensitive tumor was determined. No difference was observed in the time course of suppression and recovery between Ehrlich ascites tumor and the duodenal mucosa and bone marrow of the G.P. Swiss host. In non-tumor-bearing CD2F1 mice, the toxicity of a 2nd dose of 100 mg/kg 5-FU i.p. was found to be predictably related to the kinetic effect of a 1st dose of 100 mg/kg on [3H]UdR incorporation in the bone marrow and duodenal mucosa. In the time period from 12 hr through Day 6, when [3H]UdR incorporation into DNA rose to a maximum, administration of a 2nd dose of 5-FU was associated with 95% lethality. In contrast, during the period between 0 and 12 hr that preceded recovery of UdR incorporation, a 2nd dose resulted in less than 40% lethality, and, in the period from Day 6 through Day 8, when UdR incorporation was declining, lethality of a 2nd dose also declined to less than 25% lethality. In addition, the antitumor effectiveness of a 2nd dose of 5-FU, 100 mg/kg i.p., was predictably related to the differential effect of the 1st dose of 100 mg/kg on [3H]UdR incorporation in the P1534 tumor as compared to the host bone marrow and duodenal mucosa. Administration of a 2nd dose of 5-FU was maximally effective on Day 7, at a time when [3H]UdR incorporation was declining in the host target tissues and increasing to a maximum in the P1534 ascites tumor. Thus, the present study has demonstrated that [3H]UdR incorporation into DNA may be used to monitor the differential effect of 5-FU on tumor versus normal proliferating host tissues and, where such differences exist, to provide an in vivo method of value in designing a schedule of optimum therapeutic benefit."} {"id": "PMID:1268827", "title": "Depression of host versus graft immunity and stimulation of tumor growth following partial hepatectomy.", "content": "Tumor growth was measured in inbred (C3H and C3Hf) and hybrid (C3H X C57BL/6F1 and BALB/c X C3HF1) mice after partial hepatectomy, sham hepatectomy, and hind limb amputation. Epithelial tumors (mammary carcinoma) and mesenchymal tumors (methylcholanthrene-induced and spontaneous tissue culture) were used in order to determine the tissue specificity of the tumor growth stimulation. Immunological parameters were defined by: (a) utilization of tumors that were either antigenic or nonantigenic, and (b) measurement of the host versus graft response in partially hepatectomized mice. Partial hepatectomy and the control operations were done on the same day as the tumor cell inoculation. All tumors, regardless of their tissue type or antigenicity, grew significantly better in partially hepatectomized mice as compared with the control mice. There was a significant positive correlation between the magnitude of tumor growth stimulation and the degree of antigenicity of the tumor. Last, skin allograft survival was significantly prolonged in the hepatectomized mice. The results suggest that : (a) the stimulation of tumor growth in hepatectomized mice is not tissue specific as previously reported; and (b) the antigenicity of a tumor is not necessary for growth stimulation after partial hepatectomy.", "contents": "Depression of host versus graft immunity and stimulation of tumor growth following partial hepatectomy. Tumor growth was measured in inbred (C3H and C3Hf) and hybrid (C3H X C57BL/6F1 and BALB/c X C3HF1) mice after partial hepatectomy, sham hepatectomy, and hind limb amputation. Epithelial tumors (mammary carcinoma) and mesenchymal tumors (methylcholanthrene-induced and spontaneous tissue culture) were used in order to determine the tissue specificity of the tumor growth stimulation. Immunological parameters were defined by: (a) utilization of tumors that were either antigenic or nonantigenic, and (b) measurement of the host versus graft response in partially hepatectomized mice. Partial hepatectomy and the control operations were done on the same day as the tumor cell inoculation. All tumors, regardless of their tissue type or antigenicity, grew significantly better in partially hepatectomized mice as compared with the control mice. There was a significant positive correlation between the magnitude of tumor growth stimulation and the degree of antigenicity of the tumor. Last, skin allograft survival was significantly prolonged in the hepatectomized mice. The results suggest that : (a) the stimulation of tumor growth in hepatectomized mice is not tissue specific as previously reported; and (b) the antigenicity of a tumor is not necessary for growth stimulation after partial hepatectomy."} {"id": "PMID:1268828", "title": "Effects of prednisolone on the differentiation of mouse lung adenomas in culture.", "content": "Explants of pulmonary adenomas, induced in mice by urethan, were cultured with or without prednisolone for 72 hr. After this time, the cuboidal epithelial cells of the tumor contained many more lamellar bodies than the nonsteroid control cultures. Incorporation of labeled palmitic acid into saturated phosphatidylcholine was not significantly increased in these short-term steroid-treated cultures. The results indicate that steroid enhances the maturation of cultured pulmonary adenoma cells into cells morphologically indistinguishable from type II alveolar epithelial cells of normal lung.", "contents": "Effects of prednisolone on the differentiation of mouse lung adenomas in culture. Explants of pulmonary adenomas, induced in mice by urethan, were cultured with or without prednisolone for 72 hr. After this time, the cuboidal epithelial cells of the tumor contained many more lamellar bodies than the nonsteroid control cultures. Incorporation of labeled palmitic acid into saturated phosphatidylcholine was not significantly increased in these short-term steroid-treated cultures. The results indicate that steroid enhances the maturation of cultured pulmonary adenoma cells into cells morphologically indistinguishable from type II alveolar epithelial cells of normal lung."} {"id": "PMID:1268829", "title": "Increased growth rate of a benzo(a)pyrene-induced transplantable tumor in bursectomized chickens.", "content": "A benzo(a)pyrene-induced transplantable tumor was used to study the effects of bursectomy and thymectomy on tumor development in recipients that were isogenic with the donor for the major histocompatibility locus. Surgical bursectomies and thymectomies were done in different groups of chickens on the day of hatching, with no adjunct treatment. The following day, the experimental and control animals were given 10(3) live tumor cells s.c. Tumor frequency and size were followed weekly. With the experimental protocol used, thymectomy did not significantly affect tumor frequency or growth. Bursectomy did not affect tumor frequency, but the transplanted tumors grew significantly more rapidly in bursectomized than in control animals. Thus, bursectomy and, consequently, the antibody-forming system influence not only virus-induced tumors, but also the development of a chemical carcinogen-induced transplantable tumor line. The data underscore the host-protective role of the antibody-forming system in oncogenesis.", "contents": "Increased growth rate of a benzo(a)pyrene-induced transplantable tumor in bursectomized chickens. A benzo(a)pyrene-induced transplantable tumor was used to study the effects of bursectomy and thymectomy on tumor development in recipients that were isogenic with the donor for the major histocompatibility locus. Surgical bursectomies and thymectomies were done in different groups of chickens on the day of hatching, with no adjunct treatment. The following day, the experimental and control animals were given 10(3) live tumor cells s.c. Tumor frequency and size were followed weekly. With the experimental protocol used, thymectomy did not significantly affect tumor frequency or growth. Bursectomy did not affect tumor frequency, but the transplanted tumors grew significantly more rapidly in bursectomized than in control animals. Thus, bursectomy and, consequently, the antibody-forming system influence not only virus-induced tumors, but also the development of a chemical carcinogen-induced transplantable tumor line. The data underscore the host-protective role of the antibody-forming system in oncogenesis."} {"id": "PMID:1268830", "title": "Physicochemical alterations in the conformation of rat liver chromatin induced by carcinogens in vivo.", "content": "Administration of methylating carcinogens such as methyl methanesulfonate (120 mg/kg), dimethylnitrosamine (5 mg/kg), or methylnitrosourea (80 mg/kg) to rats resulted in an increased ellipticity in circular dichroism spectra and in an enhanced ability to bind ethidium bromide in the liver chromatin. Although shearing of the chromatin preparations increased both the ellipticity and number of binding sites for ethidium bromide, the carcinogen-induced effects were noticeable whether or not chromatin was sheared. Although the doses of the 3 carcinogens used in these studies are equivalent in their ability to induce strand breaks in liver DNA at 4 hr, their effects on the induction of conformational changes in liver chromatin are different. For example, methyl methanesulfonate induced the minimum conformational changes in liver chromatin at 4 hr, whereas methylnitrosourea induced the maximum changes at 4 hr. Methyl methanesulfonate and dimethylnitrosamine, on the other hand, induced maximum changes at 3 days. The conformational changes induced by methyl methanesulfonate and methylnitrosourea, and not by dimethylnitrosamine, tend to be repaired by 14 days.", "contents": "Physicochemical alterations in the conformation of rat liver chromatin induced by carcinogens in vivo. Administration of methylating carcinogens such as methyl methanesulfonate (120 mg/kg), dimethylnitrosamine (5 mg/kg), or methylnitrosourea (80 mg/kg) to rats resulted in an increased ellipticity in circular dichroism spectra and in an enhanced ability to bind ethidium bromide in the liver chromatin. Although shearing of the chromatin preparations increased both the ellipticity and number of binding sites for ethidium bromide, the carcinogen-induced effects were noticeable whether or not chromatin was sheared. Although the doses of the 3 carcinogens used in these studies are equivalent in their ability to induce strand breaks in liver DNA at 4 hr, their effects on the induction of conformational changes in liver chromatin are different. For example, methyl methanesulfonate induced the minimum conformational changes in liver chromatin at 4 hr, whereas methylnitrosourea induced the maximum changes at 4 hr. Methyl methanesulfonate and dimethylnitrosamine, on the other hand, induced maximum changes at 3 days. The conformational changes induced by methyl methanesulfonate and methylnitrosourea, and not by dimethylnitrosamine, tend to be repaired by 14 days."} {"id": "PMID:1268831", "title": "Test for carcinogenicity of metallic compounds by the pulmonary tumor response in strain A mice.", "content": "The production of lung adenomas in strain A mice following multiple i.p. injections of 13 metallic compounds was investigated. A significant increase in the average number of lung tumors per mouse was noted following the administration of lead subacetate, manganous sulfate, molybdenum trioxide, and nickelous acetate. These four compounds can be considered as weakly carcinogenic for lung tumors in strain A mice.", "contents": "Test for carcinogenicity of metallic compounds by the pulmonary tumor response in strain A mice. The production of lung adenomas in strain A mice following multiple i.p. injections of 13 metallic compounds was investigated. A significant increase in the average number of lung tumors per mouse was noted following the administration of lead subacetate, manganous sulfate, molybdenum trioxide, and nickelous acetate. These four compounds can be considered as weakly carcinogenic for lung tumors in strain A mice."} {"id": "PMID:1268832", "title": "In vitro labeling and gold activation autoradiography for determination of labeling index and DNA synthesis times of solid tumors.", "content": "In vitro labeling and gold activation autoradiography were used to determine the [3H]thymidine ([3H]TdR)-labeling indices and DNA synthesis times for C3H/He spontaneous mammary tumors. Three variations of the [3H]TdR, [14C]thymidine ([14C]TdR) double-labeling method, together with double-emulsion autoradiography, were used to determine the DNA synthesis times (TS). Tumors labeled totally in vivo (in vivo-in vivo method) and tumors labeled with [3H]TdR in vivo and subsequently labeled with [14C]TdR in vitro showed similar TS values. DNA synthesis times for tumors determined totally in vitro by double labeling (in vitro-in vitro method) were significantly longer than those observed in vivo; however, identical samples subjected to Hypaque-Ficoll gradient separation after double labeling showed TS's similar to those found in vivo. Furthermore, the interval between [3H]TdR and [14C]TdR administration had no effect on TS estimates in vitro. Gold activation autoradiography was used in the present experiments to reduce autoradiographic exposure times. This method, together with in vitro labeling, permits [3H]TdR labeling index and TS determinations after 6-hr and 7-day exposures, respectively.", "contents": "In vitro labeling and gold activation autoradiography for determination of labeling index and DNA synthesis times of solid tumors. In vitro labeling and gold activation autoradiography were used to determine the [3H]thymidine ([3H]TdR)-labeling indices and DNA synthesis times for C3H/He spontaneous mammary tumors. Three variations of the [3H]TdR, [14C]thymidine ([14C]TdR) double-labeling method, together with double-emulsion autoradiography, were used to determine the DNA synthesis times (TS). Tumors labeled totally in vivo (in vivo-in vivo method) and tumors labeled with [3H]TdR in vivo and subsequently labeled with [14C]TdR in vitro showed similar TS values. DNA synthesis times for tumors determined totally in vitro by double labeling (in vitro-in vitro method) were significantly longer than those observed in vivo; however, identical samples subjected to Hypaque-Ficoll gradient separation after double labeling showed TS's similar to those found in vivo. Furthermore, the interval between [3H]TdR and [14C]TdR administration had no effect on TS estimates in vitro. Gold activation autoradiography was used in the present experiments to reduce autoradiographic exposure times. This method, together with in vitro labeling, permits [3H]TdR labeling index and TS determinations after 6-hr and 7-day exposures, respectively."} {"id": "PMID:1268833", "title": "Identification of the products of mitochondrial transcription in the walker corcinosarcoma by the use of actinomycin D and ethidium bromide.", "content": "The major RNA species present in the purified mitochondrial fraction of the Walker carcinoma were investigated in order to determine which of them are located in the mitochondria and coded by the organelle DNA. The subcellular distribution of these RNA's and the in vivo sensitivity of the transcription process to selective inhibitors were examined. Among the different species separated by polyacrylamide gel electrophoresis, only the 21 and 16 Se RNA's were found exclusively in the purified mitochondria, approximately Se being the S value estimated from the relative electrophoretic mobility of the RNA. A bifid peak observed in the 16-15 Se region was shown to be an artifact caused by the ribonuclease inhibitor, naphthalene disulfonate. Ethidium bromide at high doses inhibited the incorporation in vivo of 32P into 21, 16, and 4 Se RNA, but the nuclear transcription of cytoplasmic RNA was also inhibited to the same extent. No significant effect was observed at lower doses. In contrast, actinomycin D exerted a differential inhibition of the synthesis of 28 and 18 Se RNA from both the cytoplasmic and the mitochondrial fractions, practically without affecting the transcription of the 21 and 16 Se species. The incorporation of 32P into mitochondrial 4 Se RNA was also considerably more resistant to the drug than the synthesis of the cytoplasmic tRNA. It is concluded that the 21, 16, and Se RNA's are the only major discrete species transcribed from mitochondrial DNA present in the Walker carcinoma.", "contents": "Identification of the products of mitochondrial transcription in the walker corcinosarcoma by the use of actinomycin D and ethidium bromide. The major RNA species present in the purified mitochondrial fraction of the Walker carcinoma were investigated in order to determine which of them are located in the mitochondria and coded by the organelle DNA. The subcellular distribution of these RNA's and the in vivo sensitivity of the transcription process to selective inhibitors were examined. Among the different species separated by polyacrylamide gel electrophoresis, only the 21 and 16 Se RNA's were found exclusively in the purified mitochondria, approximately Se being the S value estimated from the relative electrophoretic mobility of the RNA. A bifid peak observed in the 16-15 Se region was shown to be an artifact caused by the ribonuclease inhibitor, naphthalene disulfonate. Ethidium bromide at high doses inhibited the incorporation in vivo of 32P into 21, 16, and 4 Se RNA, but the nuclear transcription of cytoplasmic RNA was also inhibited to the same extent. No significant effect was observed at lower doses. In contrast, actinomycin D exerted a differential inhibition of the synthesis of 28 and 18 Se RNA from both the cytoplasmic and the mitochondrial fractions, practically without affecting the transcription of the 21 and 16 Se species. The incorporation of 32P into mitochondrial 4 Se RNA was also considerably more resistant to the drug than the synthesis of the cytoplasmic tRNA. It is concluded that the 21, 16, and Se RNA's are the only major discrete species transcribed from mitochondrial DNA present in the Walker carcinoma."} {"id": "PMID:1268834", "title": "Tumorigenic activity of lead chromate.", "content": "Lead chromate was investigated for its carcinogenic potential in both rats and mice. Results show that this compound is a very potent carcinogen in rats when administered i.m. Sixty-four % of the animals treated developed malignant tumors at the injection site. Three renal carcinomas were also found after i.m. treatment with lead chromate. Since lead powder is a comparatively weak carcinogen in rats, whether given p.o. or i.m., it is suggested that the combination of lead and chromium (also weak carcinogen) accounts for the high carcinogenic activity of lead chromate in rats. Swiss albino female mice could not tolerate the same high dose level as did the rats; at the lower dose administered to the mice, no tumors were detected.", "contents": "Tumorigenic activity of lead chromate. Lead chromate was investigated for its carcinogenic potential in both rats and mice. Results show that this compound is a very potent carcinogen in rats when administered i.m. Sixty-four % of the animals treated developed malignant tumors at the injection site. Three renal carcinomas were also found after i.m. treatment with lead chromate. Since lead powder is a comparatively weak carcinogen in rats, whether given p.o. or i.m., it is suggested that the combination of lead and chromium (also weak carcinogen) accounts for the high carcinogenic activity of lead chromate in rats. Swiss albino female mice could not tolerate the same high dose level as did the rats; at the lower dose administered to the mice, no tumors were detected."} {"id": "PMID:1268835", "title": "Dynamics of leukemic and normal stem cells in leukemic RFM mice.", "content": "RFM mice spontaneously develop a myelogenous leukemia that is transplantable into nonleukemic RFM mice. On transplantation, hemopoietic stem cells from leukemic mice (L-CFU-S) will seed in the spleen and grow as discrete colonies, as will hemopoietic stem cells from normal mice (N-CFU-S). As the leukemic cells used in these experiments have 39 chromosomes and normal murine cells have 40, it has been possible to estimate the numbers of N-CFU-S and L-CFU-S in RFM mice at weekly intervals after these mice had been given i.v. injections of 10(6) leukemic spleen cells (spleen cells from preterminal leukemic mice). At each study time, splenic weights, peripheral blood counts, and nucleated cell counts and colony forming units (CFU-S) of marrow, spleen, and blood were assayed. The karyotypes of dividing cells from and the histology of the resultant spleen colonies were also studied. Two weeks after the injection of leukemic spleen cells, the number of CFU-S in the marrow had increased to 3 to 10 times normal, that in the spleen to 100 times normal, and that in the blood was markedly increased. Three weeks after injection, the number of CFU-S in the marrow fell from the peak level at 2 weeks, the number in the spleen rose modestly, and the number in the blood continued to be markedly increased. A normal distribution of erythroid, myeloid, and megakaryocytic colonies was obtained from CFU-S assayed 1 week after injection of leukemic spleen cells, but from CFU-S assayed 2 or 3 weeks after injection of leukemic spleen cells, the colonies formed were comprised almost exclusively of myeloid cells. From spleen colonies formed from marrow or spleen cells obtained 1 week after the injection of leukemic spleen cells, all karyotypes contained 40 chromosomes, whereas from spleen colonies formed from marrow or spleen cells obtained 2 or 3 weeks after injection of spleen cells, almost all karyotypes contained 39 chromosomes. In contrast, most of the karyotypes found in spleen colonies formed from the injection of blood cells even 3 weeks after injection of leukemic spleen cells contained 40 chromosomes. All colonies containing cells with 39 chromosomes, leukemic colonies, contained only myeloid cells. We conclude that L-CFU-S differentiate only into the myeloid series. Early in the course of the disease there is an increase in both N-CFU-S and L-CFU-S in the spleen and marrow. As the disease progresses, the numbers of N-CFU-S in both spleen and marrow decline and, during the final week of the illness, the number of L-CFU-S in the marrow declines. The CFU-S in the peripheral blood are predominantly of normal type, even late in the disease when N-CFU-S are rare in the spleen and marrow.", "contents": "Dynamics of leukemic and normal stem cells in leukemic RFM mice. RFM mice spontaneously develop a myelogenous leukemia that is transplantable into nonleukemic RFM mice. On transplantation, hemopoietic stem cells from leukemic mice (L-CFU-S) will seed in the spleen and grow as discrete colonies, as will hemopoietic stem cells from normal mice (N-CFU-S). As the leukemic cells used in these experiments have 39 chromosomes and normal murine cells have 40, it has been possible to estimate the numbers of N-CFU-S and L-CFU-S in RFM mice at weekly intervals after these mice had been given i.v. injections of 10(6) leukemic spleen cells (spleen cells from preterminal leukemic mice). At each study time, splenic weights, peripheral blood counts, and nucleated cell counts and colony forming units (CFU-S) of marrow, spleen, and blood were assayed. The karyotypes of dividing cells from and the histology of the resultant spleen colonies were also studied. Two weeks after the injection of leukemic spleen cells, the number of CFU-S in the marrow had increased to 3 to 10 times normal, that in the spleen to 100 times normal, and that in the blood was markedly increased. Three weeks after injection, the number of CFU-S in the marrow fell from the peak level at 2 weeks, the number in the spleen rose modestly, and the number in the blood continued to be markedly increased. A normal distribution of erythroid, myeloid, and megakaryocytic colonies was obtained from CFU-S assayed 1 week after injection of leukemic spleen cells, but from CFU-S assayed 2 or 3 weeks after injection of leukemic spleen cells, the colonies formed were comprised almost exclusively of myeloid cells. From spleen colonies formed from marrow or spleen cells obtained 1 week after the injection of leukemic spleen cells, all karyotypes contained 40 chromosomes, whereas from spleen colonies formed from marrow or spleen cells obtained 2 or 3 weeks after injection of spleen cells, almost all karyotypes contained 39 chromosomes. In contrast, most of the karyotypes found in spleen colonies formed from the injection of blood cells even 3 weeks after injection of leukemic spleen cells contained 40 chromosomes. All colonies containing cells with 39 chromosomes, leukemic colonies, contained only myeloid cells. We conclude that L-CFU-S differentiate only into the myeloid series. Early in the course of the disease there is an increase in both N-CFU-S and L-CFU-S in the spleen and marrow. As the disease progresses, the numbers of N-CFU-S in both spleen and marrow decline and, during the final week of the illness, the number of L-CFU-S in the marrow declines. The CFU-S in the peripheral blood are predominantly of normal type, even late in the disease when N-CFU-S are rare in the spleen and marrow."} {"id": "PMID:1268836", "title": "Effects of manganese on carcinogenicity and metabolism of nickel subsulfide.", "content": "Nickel subsulfide, Ni3S2, alone or combined with manganese or chromium dusts, was administered i.m. to Fischer rats to study the effects of the metals upon Ni3S2 induction of sarcomas at the injection site. The incidence of sarcomas within 2 years after injection of Ni3S2 (1.2 mg) plus manganese (1.0 mg) was 7%, versus 77% in rats that received only Ni3S2 (1.2 mg), and 80% in rats that received Ni3S2 (1.2 mg) plus chromium (1.0 mg) (p less than 0.005). No local sarcomas occurred in rats that received the injection vehicle, or in rats that received manganese or chromium without Ni3S2. Admixture of manganese diminished the solubility of 63Ni3S2 in rat serum, serum ultrafiltrate, or water, in vitro. Admixture of manganese with 63Ni3S2 did not affect the mobilization or excretion of 63Ni in vivo, nor did it alter the acute pathological reactions to Ni3S2. 63Ni concentrations in ultrafiltrates of supernatant fractions of homogenates of injection sites averaged 2.8 (S. D. +/- 0.7) ng/ml at 5 to 6 months after injection of 63Ni3S2 (1.2 mg) plus manganese (1.0 mg), versus 5.4 +/- 2.0 ng/ml after injection of only 63Ni3S2 (1.2 mg) (p less than 0.02). This study demonstrates that admixture of manganese dust and Ni3S2 inhibits Ni3S2 tumorigenesis in rats, and reveals that manganese dust affects the subcellular distribution of 63Ni derived from 63Ni3S2, without influencing 63Ni kinetics as estimated by compartmental analysis.", "contents": "Effects of manganese on carcinogenicity and metabolism of nickel subsulfide. Nickel subsulfide, Ni3S2, alone or combined with manganese or chromium dusts, was administered i.m. to Fischer rats to study the effects of the metals upon Ni3S2 induction of sarcomas at the injection site. The incidence of sarcomas within 2 years after injection of Ni3S2 (1.2 mg) plus manganese (1.0 mg) was 7%, versus 77% in rats that received only Ni3S2 (1.2 mg), and 80% in rats that received Ni3S2 (1.2 mg) plus chromium (1.0 mg) (p less than 0.005). No local sarcomas occurred in rats that received the injection vehicle, or in rats that received manganese or chromium without Ni3S2. Admixture of manganese diminished the solubility of 63Ni3S2 in rat serum, serum ultrafiltrate, or water, in vitro. Admixture of manganese with 63Ni3S2 did not affect the mobilization or excretion of 63Ni in vivo, nor did it alter the acute pathological reactions to Ni3S2. 63Ni concentrations in ultrafiltrates of supernatant fractions of homogenates of injection sites averaged 2.8 (S. D. +/- 0.7) ng/ml at 5 to 6 months after injection of 63Ni3S2 (1.2 mg) plus manganese (1.0 mg), versus 5.4 +/- 2.0 ng/ml after injection of only 63Ni3S2 (1.2 mg) (p less than 0.02). This study demonstrates that admixture of manganese dust and Ni3S2 inhibits Ni3S2 tumorigenesis in rats, and reveals that manganese dust affects the subcellular distribution of 63Ni derived from 63Ni3S2, without influencing 63Ni kinetics as estimated by compartmental analysis."} {"id": "PMID:1268837", "title": "The effect of modifiers of microsomal enzymes on chemical oncogenesis in cultures of C3H mouse cell lines.", "content": "Two cell lines, both derived from the C3H mouse and each having different responses (oncogenic and cytotoxic) to polycyclic aromatic hydrocarbon oncogens, were studied with respect to their drug-metabolizing enzymes. The 10T1/2CL8 cells (a C3H mouse embryo fibroblastic cell line) were much more effective in converting 3-methylcholanthrene (3-MC) to 3-MC water-soluble metabolites, 3-MC phenols, and 3-MC-bound cellular macromolecules than were CVP3SC6 cells (a new line of C3H mouse adult ventral prostate fibroblasts). Basal aryl hydrocarbon hydroxylase activity was higher in 10T1/2CL8 cells than in CVP3SC6 cells, while the reverse was found for epoxide hydrase activity (using 3-methylcholanthrene-11, 12-oxide as substrate. 3-MC or benz(a)anthracene induced epoxide hydrase activity in both cell lines to about the same extent. 3-MC did not induce aryl hydrocarbon hydroxylase activity in CVP3SC6 cells. Aryl hydrocarbon hydroxylase activity was markedly induced in both cell lines by benz(a)anthracene and was slightly induced in 10T1/2CL8 cells by 3-MC. In a chemical oncogenesis cell culture system, transformation of 10T1/2CL8 cells mediated by 3-MC could be increased two- to threefold by treating the cell cultures with: either benz(a)anthracene, styrene oxide, cyclohexene oxide, or 1,2,3,4-tetrahydrona=phthalene-1,2-oxide; or with cyclohexene or 1,2-dihydrona-phthalene, alkene precursors of cyclohexene oxide and 1,2,3,4-tetrahydronaphthalene-1,2-oxide, respectively. When 10T1/2CL8 cells were treated with a combination of benz(a)anthracene and cyclohexene, 3-MC-mediated transformation was increased 7.8-fold. CVP3SC6 cells that were not transformed by 3-MC or other hydrocarbon oncogens were transformed by a combined treatment with benz(a)anthracene, 1,2-dihydronaphthalene, and 3-MC.", "contents": "The effect of modifiers of microsomal enzymes on chemical oncogenesis in cultures of C3H mouse cell lines. Two cell lines, both derived from the C3H mouse and each having different responses (oncogenic and cytotoxic) to polycyclic aromatic hydrocarbon oncogens, were studied with respect to their drug-metabolizing enzymes. The 10T1/2CL8 cells (a C3H mouse embryo fibroblastic cell line) were much more effective in converting 3-methylcholanthrene (3-MC) to 3-MC water-soluble metabolites, 3-MC phenols, and 3-MC-bound cellular macromolecules than were CVP3SC6 cells (a new line of C3H mouse adult ventral prostate fibroblasts). Basal aryl hydrocarbon hydroxylase activity was higher in 10T1/2CL8 cells than in CVP3SC6 cells, while the reverse was found for epoxide hydrase activity (using 3-methylcholanthrene-11, 12-oxide as substrate. 3-MC or benz(a)anthracene induced epoxide hydrase activity in both cell lines to about the same extent. 3-MC did not induce aryl hydrocarbon hydroxylase activity in CVP3SC6 cells. Aryl hydrocarbon hydroxylase activity was markedly induced in both cell lines by benz(a)anthracene and was slightly induced in 10T1/2CL8 cells by 3-MC. In a chemical oncogenesis cell culture system, transformation of 10T1/2CL8 cells mediated by 3-MC could be increased two- to threefold by treating the cell cultures with: either benz(a)anthracene, styrene oxide, cyclohexene oxide, or 1,2,3,4-tetrahydrona=phthalene-1,2-oxide; or with cyclohexene or 1,2-dihydrona-phthalene, alkene precursors of cyclohexene oxide and 1,2,3,4-tetrahydronaphthalene-1,2-oxide, respectively. When 10T1/2CL8 cells were treated with a combination of benz(a)anthracene and cyclohexene, 3-MC-mediated transformation was increased 7.8-fold. CVP3SC6 cells that were not transformed by 3-MC or other hydrocarbon oncogens were transformed by a combined treatment with benz(a)anthracene, 1,2-dihydronaphthalene, and 3-MC."} {"id": "PMID:1268838", "title": "Clinical evaluation of ftorafur (pyrimidine-deoxyribose n1-2'-furanidyl-5-fluorouracil).", "content": "Ftorafur, a possible sustained-release formulation of 5-fluorouracil, was administered to 27 patients with metastatic cancers. The majority of patients had adenocarcinoma, most of which (60%) arose from the gastrointestinal tract. Ftorafur was given i.v. at doses ranging from 1 to 3 g/sq m/day for 5 days, repeated every 2 to 3 weeks. Gastrointestinal (68%) and neurological (17%) toxicities were the most common side effects encountered in this study and became dose limiting at doses greater than 2 g/sq m/day for 5 days. Myelosuppression (7%) was infrequent. Other toxicities included weakness (20%), chills and fever (8%), and phlebitis (1%). Of 24 evaluable patients, 4 (17%) responded (1 complete and 3 partial remissions). Responses were seen in 1 of 8 carcinomas of the lung, 1 of 5 carcinomas of the stomach, 1 of 3 carcinomas of the colon, and 1 of 1 carcinoma of the jejunum. The duration of response ranged from 4 to 58 weeks. The results of this study resemble somewhat those obtained with the laborious 5-day continuous i.v. infusion of 5-fluorouracil. Daily doses of 2 g/sq m for 5 days, repeated every 3 weeks, produced significant antitumor effect and tolerable toxicity.", "contents": "Clinical evaluation of ftorafur (pyrimidine-deoxyribose n1-2'-furanidyl-5-fluorouracil). Ftorafur, a possible sustained-release formulation of 5-fluorouracil, was administered to 27 patients with metastatic cancers. The majority of patients had adenocarcinoma, most of which (60%) arose from the gastrointestinal tract. Ftorafur was given i.v. at doses ranging from 1 to 3 g/sq m/day for 5 days, repeated every 2 to 3 weeks. Gastrointestinal (68%) and neurological (17%) toxicities were the most common side effects encountered in this study and became dose limiting at doses greater than 2 g/sq m/day for 5 days. Myelosuppression (7%) was infrequent. Other toxicities included weakness (20%), chills and fever (8%), and phlebitis (1%). Of 24 evaluable patients, 4 (17%) responded (1 complete and 3 partial remissions). Responses were seen in 1 of 8 carcinomas of the lung, 1 of 5 carcinomas of the stomach, 1 of 3 carcinomas of the colon, and 1 of 1 carcinoma of the jejunum. The duration of response ranged from 4 to 58 weeks. The results of this study resemble somewhat those obtained with the laborious 5-day continuous i.v. infusion of 5-fluorouracil. Daily doses of 2 g/sq m for 5 days, repeated every 3 weeks, produced significant antitumor effect and tolerable toxicity."} {"id": "PMID:1268839", "title": "Stimulation or inhibition of immune resistance against metastatic or local growth of a C3H mammary carcinoma.", "content": "The effects of syngeneic tumor vaccine preparations on resistance against s.c. and pulmonary implants of a spontaneous C3H mouse mammary carcinoma have been compared during progressive primary tumor growth, after surgical cure, and during declining immune resistance following complete tumor removal. Concomitant antitumor immunity reached a higher level of effectiveness in the lungs than in s.c. tissue. The concomitant immune resistance in the lungs also remained effective longer than did s.c. resistance, which was the first to decline under the increasing antigen burden of a growing tumor implant. Resistance to challenge recovered quickly after the complete removal of a large tumor burden, but recovery was impeded if killed tumor tissue was reinjected too soon after tumor removal. If injections of killed tumor tissue were given 7 days after tumor removal, the completed recovery was not affected. If injections of killed tumor tissue were given 30 days after tumor removal, immune resistance to challenge, at this time much declined, was stimulated.", "contents": "Stimulation or inhibition of immune resistance against metastatic or local growth of a C3H mammary carcinoma. The effects of syngeneic tumor vaccine preparations on resistance against s.c. and pulmonary implants of a spontaneous C3H mouse mammary carcinoma have been compared during progressive primary tumor growth, after surgical cure, and during declining immune resistance following complete tumor removal. Concomitant antitumor immunity reached a higher level of effectiveness in the lungs than in s.c. tissue. The concomitant immune resistance in the lungs also remained effective longer than did s.c. resistance, which was the first to decline under the increasing antigen burden of a growing tumor implant. Resistance to challenge recovered quickly after the complete removal of a large tumor burden, but recovery was impeded if killed tumor tissue was reinjected too soon after tumor removal. If injections of killed tumor tissue were given 7 days after tumor removal, the completed recovery was not affected. If injections of killed tumor tissue were given 30 days after tumor removal, immune resistance to challenge, at this time much declined, was stimulated."} {"id": "PMID:1268843", "title": "Inhibitory effect of Capsella bursa-pastoris extract on growth of Ehrlich solid tumor in mice.", "content": "The treatment of ICR mice with i.p. injections (0.14 g/kg/day) of the extract of Capsella bursa-pastoris herb (Cruciferae) caused 50 to 80% inhibition of the solid growth of Ehrlich tumor cells that had been inoculated into the s.c. tissue of the animals. The tumor lumps in the treated mice showed multifocal necroses and the infiltartion of host fibrous tissue cells. Experiments were also performed to isolate and identify the active component for the antitumor action, and an acidic substance was isolated in crystalline form from the herb extract. This acidic substance was identified as fumaric acid and was effective in inhibiting the growth of Ehrlich solid tumor at a dose of 10 mg/kg/day. The 50% lethal dose (i.p.) of this acid was 266 mg/kg.", "contents": "Inhibitory effect of Capsella bursa-pastoris extract on growth of Ehrlich solid tumor in mice. The treatment of ICR mice with i.p. injections (0.14 g/kg/day) of the extract of Capsella bursa-pastoris herb (Cruciferae) caused 50 to 80% inhibition of the solid growth of Ehrlich tumor cells that had been inoculated into the s.c. tissue of the animals. The tumor lumps in the treated mice showed multifocal necroses and the infiltartion of host fibrous tissue cells. Experiments were also performed to isolate and identify the active component for the antitumor action, and an acidic substance was isolated in crystalline form from the herb extract. This acidic substance was identified as fumaric acid and was effective in inhibiting the growth of Ehrlich solid tumor at a dose of 10 mg/kg/day. The 50% lethal dose (i.p.) of this acid was 266 mg/kg."} {"id": "PMID:1268844", "title": "Demonstration of fibrin in early stages of experimental metastases.", "content": "Tumor emboli were produced in lungs of Sprague-Dawley rats by i.v. injection of Walker 256 tumor cells into the tail vein. Tissues were examined by electron microscopy at periods from 30 sec to 72 hr after tumor injection. Two methods of conventional staining were used, in addition to immunoperoxidase techniques, with antifibrin antibodies produced in rabbits. Tumor cells accompanied by a platelet mass were seen in pulmonary arterioles at the earliest time period (30 sec). By conventional staining, small amounts of fibrin were detected within the platelet clumps by 5 min after inoculation. Periodicity indicating stable fibrin was not seen by this technique until 15 to 45 min. When peroxidase-labeled antibody was applied to tissue, sections showed fibrin-positive material at 30 sec, and periodicity of fibrin was detected by 5 min. Fibrin reached a maximum by both techniques at about 1 hr and disappeared, along with the platelets, at about 9 hr. When fibrinolysin was injected prior to the tumor cell inoculation, platelets and fibrin were either absent or present only in traces, and no stable fibrin was detected. These observations show that fibrin occurs very early in small amounts in association with tumor cell emboli, and is removed while the cells are still intravascular.", "contents": "Demonstration of fibrin in early stages of experimental metastases. Tumor emboli were produced in lungs of Sprague-Dawley rats by i.v. injection of Walker 256 tumor cells into the tail vein. Tissues were examined by electron microscopy at periods from 30 sec to 72 hr after tumor injection. Two methods of conventional staining were used, in addition to immunoperoxidase techniques, with antifibrin antibodies produced in rabbits. Tumor cells accompanied by a platelet mass were seen in pulmonary arterioles at the earliest time period (30 sec). By conventional staining, small amounts of fibrin were detected within the platelet clumps by 5 min after inoculation. Periodicity indicating stable fibrin was not seen by this technique until 15 to 45 min. When peroxidase-labeled antibody was applied to tissue, sections showed fibrin-positive material at 30 sec, and periodicity of fibrin was detected by 5 min. Fibrin reached a maximum by both techniques at about 1 hr and disappeared, along with the platelets, at about 9 hr. When fibrinolysin was injected prior to the tumor cell inoculation, platelets and fibrin were either absent or present only in traces, and no stable fibrin was detected. These observations show that fibrin occurs very early in small amounts in association with tumor cell emboli, and is removed while the cells are still intravascular."} {"id": "PMID:1268845", "title": "Frequency of antibody to a virus-induced tumor-associated antigen (AG-4) in Japanese sera from patients with cervical cancer and controls.", "content": "Microquantitative complement fixation was used to detect antibody to AG-4, a tumor-associated herpesvirus type 2-induced antigen, in sera from Japanese patients with cervical neoplasia. The prevalence of antibody to AG-4 in cervical cancer patients is 47% as compared to 7% in control women. That AG-4 antibody is less prevalent in Japanese than in American cancer patients reflects the frequency of genital herpesvirus type 2 infections in Japan. These findings confirm the association of AG-4 with cervical cancer in a proportion of Japanese patients with neoplastic disease; they implicate factors other than herpesvirus type 2 in another proportion of cervical cancer patients. The possibility that herpesvirus type 1 is one of these factors is considered.", "contents": "Frequency of antibody to a virus-induced tumor-associated antigen (AG-4) in Japanese sera from patients with cervical cancer and controls. Microquantitative complement fixation was used to detect antibody to AG-4, a tumor-associated herpesvirus type 2-induced antigen, in sera from Japanese patients with cervical neoplasia. The prevalence of antibody to AG-4 in cervical cancer patients is 47% as compared to 7% in control women. That AG-4 antibody is less prevalent in Japanese than in American cancer patients reflects the frequency of genital herpesvirus type 2 infections in Japan. These findings confirm the association of AG-4 with cervical cancer in a proportion of Japanese patients with neoplastic disease; they implicate factors other than herpesvirus type 2 in another proportion of cervical cancer patients. The possibility that herpesvirus type 1 is one of these factors is considered."} {"id": "PMID:1268846", "title": "Methylation analysis of the carbohydrate portion of carcinoembryonic antigen.", "content": "The carbohydrate structural units of carcinoembryonic antigen samples isolated from four different tumors were quantitated using gas chromatography-mass spectrometery after methylation and subsequent conversion to their alditol acetates. Different carcinoembryonic antigen preparations showed some quantitative but no qualitative differences in the structural units present. The results indicate that a large portion of the fucose residues in the glycoprotein were linked to N-acetylglucosamine and that most of the branching mannose residues were probably linked to three N-acetylglucosamine residues.", "contents": "Methylation analysis of the carbohydrate portion of carcinoembryonic antigen. The carbohydrate structural units of carcinoembryonic antigen samples isolated from four different tumors were quantitated using gas chromatography-mass spectrometery after methylation and subsequent conversion to their alditol acetates. Different carcinoembryonic antigen preparations showed some quantitative but no qualitative differences in the structural units present. The results indicate that a large portion of the fucose residues in the glycoprotein were linked to N-acetylglucosamine and that most of the branching mannose residues were probably linked to three N-acetylglucosamine residues."} {"id": "PMID:1268847", "title": "Resistance of human melanoma cells to ultraviolet radiation.", "content": "A series of five human melanoma cell lines has been demonstrated to be highly resistant to ultraviolet (UV) radiation, with a D0 of 400 ergs/sq mm. Melanotic melanoma cells were found to increase their production of melanin following UV radiation, whereas some amelanotic cells did not. Melanotic and amelanotic melanoma cell lines exhibited the same UV resistance; melanoma and nonmelanoma cells formed the same numbers of thymine dimers at a given UV dose. These data imply that melanin does not play a major role in protecting DNA of melanoma cells against UV damage in culture. The rates of removal of thymine dimers from DNA of melanoma cells were comparable to those in UV-sensitive, nonmelanoma cell lines, so that rapid excision repair does not explain UV resistnace in the melanoma cells. No DNA strand breakage was detected in a melanoma cell line at moderate UV doses.", "contents": "Resistance of human melanoma cells to ultraviolet radiation. A series of five human melanoma cell lines has been demonstrated to be highly resistant to ultraviolet (UV) radiation, with a D0 of 400 ergs/sq mm. Melanotic melanoma cells were found to increase their production of melanin following UV radiation, whereas some amelanotic cells did not. Melanotic and amelanotic melanoma cell lines exhibited the same UV resistance; melanoma and nonmelanoma cells formed the same numbers of thymine dimers at a given UV dose. These data imply that melanin does not play a major role in protecting DNA of melanoma cells against UV damage in culture. The rates of removal of thymine dimers from DNA of melanoma cells were comparable to those in UV-sensitive, nonmelanoma cell lines, so that rapid excision repair does not explain UV resistnace in the melanoma cells. No DNA strand breakage was detected in a melanoma cell line at moderate UV doses."} {"id": "PMID:1268848", "title": "Transplantation resistance to mouse ependymoblastoma following immunization with dehistonized syngeneic tumor chromatin.", "content": "Female C57BL/J6 mice pretreated with dehistonized ependymoblastoma chromatin rejected 5 x 10(4) or 10(5) s.c.-implanted syngeneic ependymoblastoma cells. Control mice that received Freund's adjuvant containing dehistonized chromatin from normal mouse brain developed palpable tumor nodules in 90% and 35 to 45% of the animals, respectively. Increased binding of spleen lymphocytes from mice pretreated with dehistonized tumor chromatin to Sepharose 4B coupled with components of dehistonized tumor chromatin was observed. This provides initial evidence for the presence of \"committed\" lymphocytes in mice pretreated with dehistonized chromatin from this mouse ependymoblastoma.", "contents": "Transplantation resistance to mouse ependymoblastoma following immunization with dehistonized syngeneic tumor chromatin. Female C57BL/J6 mice pretreated with dehistonized ependymoblastoma chromatin rejected 5 x 10(4) or 10(5) s.c.-implanted syngeneic ependymoblastoma cells. Control mice that received Freund's adjuvant containing dehistonized chromatin from normal mouse brain developed palpable tumor nodules in 90% and 35 to 45% of the animals, respectively. Increased binding of spleen lymphocytes from mice pretreated with dehistonized tumor chromatin to Sepharose 4B coupled with components of dehistonized tumor chromatin was observed. This provides initial evidence for the presence of \"committed\" lymphocytes in mice pretreated with dehistonized chromatin from this mouse ependymoblastoma."} {"id": "PMID:1268849", "title": "The differential effects of chemical carcinogens on vitamin A status and on microsomal drug metabolism in normal and vitamin A-deficient rats.", "content": "Male Sprague-Dawley rats were maintained on a vitamin A-deficient diet for 5 weeks. Although serum and hepatic levels of vitamin A were significantly lower at this time, no outward signs of vitamin A deficiency were present. Hepatic microsomal levels of cytochrome P-450 in the vitamin A-deficient animals were 70% that of the control animals. Of the three microsomal enzymes studied, ethylmorphine N-demethylase, aniline hydroxylase, and aminopyrine N-demethylase, only the last one was adversely affected by vitamin A deficiency. 3-Methylcholanthrene, phenobarbital, and 2-acetylaminofluorene had a greater inductive effect and cytochrome P-450 in vitamin A-deficient rats. 4-Dimethylaminoazobenzene treatment decreased in the level of cytochrome P-450 in control rats more than in deficieny rats. The hepatic concentration of vitamin A was significantly reduced in control rats that were given injections of 3-methylcholanthrene, 2-acetylaminofluorene, or phenobarbital. Benzo(a)pyrene and 4-dimethylaminoazobenzene had less effect.", "contents": "The differential effects of chemical carcinogens on vitamin A status and on microsomal drug metabolism in normal and vitamin A-deficient rats. Male Sprague-Dawley rats were maintained on a vitamin A-deficient diet for 5 weeks. Although serum and hepatic levels of vitamin A were significantly lower at this time, no outward signs of vitamin A deficiency were present. Hepatic microsomal levels of cytochrome P-450 in the vitamin A-deficient animals were 70% that of the control animals. Of the three microsomal enzymes studied, ethylmorphine N-demethylase, aniline hydroxylase, and aminopyrine N-demethylase, only the last one was adversely affected by vitamin A deficiency. 3-Methylcholanthrene, phenobarbital, and 2-acetylaminofluorene had a greater inductive effect and cytochrome P-450 in vitamin A-deficient rats. 4-Dimethylaminoazobenzene treatment decreased in the level of cytochrome P-450 in control rats more than in deficieny rats. The hepatic concentration of vitamin A was significantly reduced in control rats that were given injections of 3-methylcholanthrene, 2-acetylaminofluorene, or phenobarbital. Benzo(a)pyrene and 4-dimethylaminoazobenzene had less effect."} {"id": "PMID:1268850", "title": "Development of an assay for aryl hydrocarbon (benzo(a)pyrene) hydroxylase in human peripheral blood monocytes.", "content": "An assay has been developed and measurements of aryl hydrocarbon [benzo(a)pyrene] hydroxylase have been made in peripheral blood monocytes from a human population. Treatment with benz(a)anthracene in cell culture increased aryl hydrocarbon hydroxylase activity from 6.5 to 37-fold in monocytes from each of 25 apparently healthy donors. A weak correlation (r = 0.38) was observed between the induction ratios obtained with monocytes and lymphocytes from the same donors. Reproducibilities of the monocyte and lymphocyte assays were comparable. In monocytes, the measurement of basal and induced aryl hydrocarbon hydroxylases activity does not require pretreatment with mitogens as is the case with lymphocytes. Monocytes also exhibit a much wider range of induction ratios than do lymphocytes.", "contents": "Development of an assay for aryl hydrocarbon (benzo(a)pyrene) hydroxylase in human peripheral blood monocytes. An assay has been developed and measurements of aryl hydrocarbon [benzo(a)pyrene] hydroxylase have been made in peripheral blood monocytes from a human population. Treatment with benz(a)anthracene in cell culture increased aryl hydrocarbon hydroxylase activity from 6.5 to 37-fold in monocytes from each of 25 apparently healthy donors. A weak correlation (r = 0.38) was observed between the induction ratios obtained with monocytes and lymphocytes from the same donors. Reproducibilities of the monocyte and lymphocyte assays were comparable. In monocytes, the measurement of basal and induced aryl hydrocarbon hydroxylases activity does not require pretreatment with mitogens as is the case with lymphocytes. Monocytes also exhibit a much wider range of induction ratios than do lymphocytes."} {"id": "PMID:1268851", "title": "The effect of adriamycin on the cell cycle traverse of a human lymphoid cell line.", "content": "The kinetic response of a human lymphoma cell line to adriamycin was analyzed by means of pulse cytophotometry. Depending on concentration and exposure time, cell cycle progression was delayed in G1, S, and G2 phases. There was a differential sensitivity for the interaction of adriamycin with the transit through these phases. G2 arrest could be induced by low concentrations of adriamycin, whereas the block in G1 was exerted only after long-term treatment with high concentrations and was completely reversible after drug removal. Delay in S-phase transit was transient in spite of continuous exposure to high concentrations of adriamycin. Thus, concentration and duration of treatment determined the magnitude of G2 arrest as well as onset and rate of G2 accumulation due to progression delay in G1 and S phases. Cell age had only little influence on the degree of subsequent G2 arrest. Irreversibility of the G2 block strongly suggests eventual cell death in G2 phase, which may be utilized as a predictive test for response to adriamycin in vivo.", "contents": "The effect of adriamycin on the cell cycle traverse of a human lymphoid cell line. The kinetic response of a human lymphoma cell line to adriamycin was analyzed by means of pulse cytophotometry. Depending on concentration and exposure time, cell cycle progression was delayed in G1, S, and G2 phases. There was a differential sensitivity for the interaction of adriamycin with the transit through these phases. G2 arrest could be induced by low concentrations of adriamycin, whereas the block in G1 was exerted only after long-term treatment with high concentrations and was completely reversible after drug removal. Delay in S-phase transit was transient in spite of continuous exposure to high concentrations of adriamycin. Thus, concentration and duration of treatment determined the magnitude of G2 arrest as well as onset and rate of G2 accumulation due to progression delay in G1 and S phases. Cell age had only little influence on the degree of subsequent G2 arrest. Irreversibility of the G2 block strongly suggests eventual cell death in G2 phase, which may be utilized as a predictive test for response to adriamycin in vivo."} {"id": "PMID:1268852", "title": "Influence of glucocorticoid, estrogen, and androgen hormones on transformation of human cells in vitro by feline sarcoma virus.", "content": "Infection of human foreskin cells (D-550) by the Snyder-Theilen strain of feline sarcoma virus produced small but countable foci and demonstrated \"single-hit\" dose-response kinetics. Significant quantitative and qualitative enhancement of focus formation was observed when the glucocorticoid hormones, dexamethasone, hydrocortisone, cortisol acetate, and prednisolone were added to cell cultures (1.0 mug/ml) 24 hr postinfection. However, aldosterone, while inducing qualitatively larger foci, did not bring about a quantitative enhancement in total foci number. By contrast, 17beta-estradiol, progesterone, cortisone acetate, methyltestosterone, and estrone elicited little or no effect on focus induction by Snyder-Theilen feline sarcoma virus. Evidence is suggestive of a posttranscriptional effect possibly modulating viral genome expression resulting in an increased efficiency of viral transformation, and an increased proliferation of transformed cells.", "contents": "Influence of glucocorticoid, estrogen, and androgen hormones on transformation of human cells in vitro by feline sarcoma virus. Infection of human foreskin cells (D-550) by the Snyder-Theilen strain of feline sarcoma virus produced small but countable foci and demonstrated \"single-hit\" dose-response kinetics. Significant quantitative and qualitative enhancement of focus formation was observed when the glucocorticoid hormones, dexamethasone, hydrocortisone, cortisol acetate, and prednisolone were added to cell cultures (1.0 mug/ml) 24 hr postinfection. However, aldosterone, while inducing qualitatively larger foci, did not bring about a quantitative enhancement in total foci number. By contrast, 17beta-estradiol, progesterone, cortisone acetate, methyltestosterone, and estrone elicited little or no effect on focus induction by Snyder-Theilen feline sarcoma virus. Evidence is suggestive of a posttranscriptional effect possibly modulating viral genome expression resulting in an increased efficiency of viral transformation, and an increased proliferation of transformed cells."} {"id": "PMID:1268853", "title": "Electrocardiographic and pathological studies of the heart in experimental guinea pig leukemia.", "content": "Electrocardiographic tracings were performed on 26 strain 2 guinea pigs in which leukemia was induced by inoculation of L2C leukemic cells. All inoculated animals developed leukemia. In terminal phases of this disease significant electrocardiographic changes were observed in 20 of the 26 animals; in 5 animals the electrocardiograms were normal and in 1 guinea pig the changes were borderline. The most significant changes consisted of the onset of a Q-wave or a T-wave inversion or both. Pathological examination of the heart removed in the terminal phase of the disease revealed infiltration of the endocardium and epicardium and in the capillaries of the myocardium. Such areas of infiltration, when viewed with the electron microscope, revealed the presence of leukemic cells within the lumen of capillaries and in areas immediately surrounding the capillaries. Infiltration of myocardial fibers was not observed. The electrocardiographic changes observed in guinea pig leukemia may be related to the leukemic infiltration of myocardial capillaries and the resulting anoxia.", "contents": "Electrocardiographic and pathological studies of the heart in experimental guinea pig leukemia. Electrocardiographic tracings were performed on 26 strain 2 guinea pigs in which leukemia was induced by inoculation of L2C leukemic cells. All inoculated animals developed leukemia. In terminal phases of this disease significant electrocardiographic changes were observed in 20 of the 26 animals; in 5 animals the electrocardiograms were normal and in 1 guinea pig the changes were borderline. The most significant changes consisted of the onset of a Q-wave or a T-wave inversion or both. Pathological examination of the heart removed in the terminal phase of the disease revealed infiltration of the endocardium and epicardium and in the capillaries of the myocardium. Such areas of infiltration, when viewed with the electron microscope, revealed the presence of leukemic cells within the lumen of capillaries and in areas immediately surrounding the capillaries. Infiltration of myocardial fibers was not observed. The electrocardiographic changes observed in guinea pig leukemia may be related to the leukemic infiltration of myocardial capillaries and the resulting anoxia."} {"id": "PMID:1268854", "title": "Growth support of small B16 melanoma implants with nitrosourea-sterilized fractions of the same tumor.", "content": "B16 melanoma cells sterilized in vitro with 1,3-bis(2-chloroethyl)-1-nitrosourea or in vivo with trans-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, have been used to enhance the percentage of tumor takes with small s.c. implants of viable cells and to reduce the latent period between tumor implantation and palpability. The admixture of trans-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea-inactivated cells with viable cell implants reduced the number of cells required to produce tumors in 50% of the animals by approximately 3 log10 units and markedly reduced the time of tumor appearance from implants of up to 10(6) cells. Similar results were obtained with 1,3-bis(2-chloroethyl)-1-nitrosourea-sterilized cells. The growth-supporting effect obtained with the nitrosourea-inactivated cells appeared to be as pronounced as that previously reported, for this tumor system, with radiation-inactivated cells.", "contents": "Growth support of small B16 melanoma implants with nitrosourea-sterilized fractions of the same tumor. B16 melanoma cells sterilized in vitro with 1,3-bis(2-chloroethyl)-1-nitrosourea or in vivo with trans-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, have been used to enhance the percentage of tumor takes with small s.c. implants of viable cells and to reduce the latent period between tumor implantation and palpability. The admixture of trans-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea-inactivated cells with viable cell implants reduced the number of cells required to produce tumors in 50% of the animals by approximately 3 log10 units and markedly reduced the time of tumor appearance from implants of up to 10(6) cells. Similar results were obtained with 1,3-bis(2-chloroethyl)-1-nitrosourea-sterilized cells. The growth-supporting effect obtained with the nitrosourea-inactivated cells appeared to be as pronounced as that previously reported, for this tumor system, with radiation-inactivated cells."} {"id": "PMID:1268855", "title": "Specific potentiation of L1210 vaccine by pyran copolymer.", "content": "Pyran copolymer (NSC 46015) was found to potentiate strongly the immune response of C57BL/6J X DBA/2 F1 mice to 10(4) live L1210 tumor cells following suboptimal vaccination with 10(7) radiation-inactivated L1210 cells. Optimal immunity to challenge was produced by concomitant i.p administration of pyran and L1210 vaccine, and activity was dependent upon both pyran and vaccine dosages. In addition, this immunopotentiation seemed to be related to the intrinsic viscosity of different pyran preparations tested, although all the pyran compounds had significant activity. Furthermore, the increased immunity of subsequent live tumor challenge appeared to be specific for the vaccinating cell type.", "contents": "Specific potentiation of L1210 vaccine by pyran copolymer. Pyran copolymer (NSC 46015) was found to potentiate strongly the immune response of C57BL/6J X DBA/2 F1 mice to 10(4) live L1210 tumor cells following suboptimal vaccination with 10(7) radiation-inactivated L1210 cells. Optimal immunity to challenge was produced by concomitant i.p administration of pyran and L1210 vaccine, and activity was dependent upon both pyran and vaccine dosages. In addition, this immunopotentiation seemed to be related to the intrinsic viscosity of different pyran preparations tested, although all the pyran compounds had significant activity. Furthermore, the increased immunity of subsequent live tumor challenge appeared to be specific for the vaccinating cell type."} {"id": "PMID:1268856", "title": "Decreased lymphocyte adenosine deaminase activity in tumor patients.", "content": "Adenosine deaminase has been measured in the lymphocytes of individuals with various types of solid tumors. The mean activity was found to be significantly lower when compared with control individuals of a similar age.", "contents": "Decreased lymphocyte adenosine deaminase activity in tumor patients. Adenosine deaminase has been measured in the lymphocytes of individuals with various types of solid tumors. The mean activity was found to be significantly lower when compared with control individuals of a similar age."} {"id": "PMID:1268857", "title": "Thymic hormone modulation of leukemogenic virus replication.", "content": "The effect of purified calf thymus extract, thymosin, on infection with murine leukemia virus (MuLV) (Rauscher) was studied in adult thymectomized BALB/c mice. The course of infection was determined by virus titer in the blood plasma, by enumeration of spleen cells replicating MuLV (i.e., infectious centers), and by the examination of cells for expression of virus-induced cell membrane antigen. Thymectomy (performed 1 week prior to the virus injection) decreased MuLV infection by all three parameters. However, administration of thymosin (500 mug, given in equal doses 2 days before and at the time of injection of virus) caused a marked increase of plasma titer of virus, as well as an increased number of spleen cells generating MuLV as compared to controls treated either with purified spleen fraction or with diluent (buffered salt solution). More than two doses of thymic extract (up to nine, given every 2 days after infection) had no further effect on plasma virus titer or number of splenic infectious centers. Furthermore, treatment of mice with either thymic or splenic extracts increased the incidence of virus related membrane antigen appearing on the surface of spleen cells, as compared to diluent-treated control animals. These results indicate that thymosin may enhance infection by or replication of murine oncornaviruses.", "contents": "Thymic hormone modulation of leukemogenic virus replication. The effect of purified calf thymus extract, thymosin, on infection with murine leukemia virus (MuLV) (Rauscher) was studied in adult thymectomized BALB/c mice. The course of infection was determined by virus titer in the blood plasma, by enumeration of spleen cells replicating MuLV (i.e., infectious centers), and by the examination of cells for expression of virus-induced cell membrane antigen. Thymectomy (performed 1 week prior to the virus injection) decreased MuLV infection by all three parameters. However, administration of thymosin (500 mug, given in equal doses 2 days before and at the time of injection of virus) caused a marked increase of plasma titer of virus, as well as an increased number of spleen cells generating MuLV as compared to controls treated either with purified spleen fraction or with diluent (buffered salt solution). More than two doses of thymic extract (up to nine, given every 2 days after infection) had no further effect on plasma virus titer or number of splenic infectious centers. Furthermore, treatment of mice with either thymic or splenic extracts increased the incidence of virus related membrane antigen appearing on the surface of spleen cells, as compared to diluent-treated control animals. These results indicate that thymosin may enhance infection by or replication of murine oncornaviruses."} {"id": "PMID:1268858", "title": "Bioassay for quantitating circulating tumor cells in a syngeneic mouse tumor system.", "content": "A bioassay is described for the quantitation of tumor cells in blood specimens in a syngeneic mouse tumor system (Sarcoma 1 in A/J mice). The procedure involved i.m. injection of blood containing tumor cells into each thigh of normal recipient mice and, 14 days later, examination of the sites of injection for evidence of tumor growth. For each specimen, a tumor index was calculated based on the number of tumor takes and the size of the tumors. The number of tumor cells was determined by comparison with tumor indices from standard specimens with known number of tumor cells. Optimal conditions for this assay were investigated. We have used this bioassay to quantitate tumor cells in the venous blood of tumor-bearing animals under various treatments and manipulations. At the same time, the incidence of regional node metastasis was obtained by direct histological examination. Surgical removal of a well-established primary tumor enhanced the dissemination of the tumor, as evidenced by an increased incidence in regional node metastasis and an increase in the number of tumor cells reaching the venous circulation. Similar results were obtained when the tumor-bearing feet were ligated to produce ischemia of the primary tumor. Repeated physical trauma to the primary tumor resulted in increased dissemination of tumor cells into the venous circulation, but it did not increase the incidence of regional node metastasis. Immunosuppression of the tumor-bearing animals increased the dissemination of tumor cells, whereas immunostimulation decreased the dissemination.", "contents": "Bioassay for quantitating circulating tumor cells in a syngeneic mouse tumor system. A bioassay is described for the quantitation of tumor cells in blood specimens in a syngeneic mouse tumor system (Sarcoma 1 in A/J mice). The procedure involved i.m. injection of blood containing tumor cells into each thigh of normal recipient mice and, 14 days later, examination of the sites of injection for evidence of tumor growth. For each specimen, a tumor index was calculated based on the number of tumor takes and the size of the tumors. The number of tumor cells was determined by comparison with tumor indices from standard specimens with known number of tumor cells. Optimal conditions for this assay were investigated. We have used this bioassay to quantitate tumor cells in the venous blood of tumor-bearing animals under various treatments and manipulations. At the same time, the incidence of regional node metastasis was obtained by direct histological examination. Surgical removal of a well-established primary tumor enhanced the dissemination of the tumor, as evidenced by an increased incidence in regional node metastasis and an increase in the number of tumor cells reaching the venous circulation. Similar results were obtained when the tumor-bearing feet were ligated to produce ischemia of the primary tumor. Repeated physical trauma to the primary tumor resulted in increased dissemination of tumor cells into the venous circulation, but it did not increase the incidence of regional node metastasis. Immunosuppression of the tumor-bearing animals increased the dissemination of tumor cells, whereas immunostimulation decreased the dissemination."} {"id": "PMID:1268859", "title": "Tumorigenicity in vivo and induction of malignant transformation and mutagenesis in cell cultures by adriamycin and daunomycin.", "content": "The two anthracycline antitumor antibiotics, adriamycin and daunomycin, have been tested for tumorigenic activity, and the results confirm previous findings that they can induce mammary tumors in female rats receiving single i.v. doses. Both substances are highly potent in producing malignant transformation and mutation in mammalian cell systems in vitro. Their transformming activity is comparable to that of the potent carcinogen, N-methyl-N'-nitro-N-nitro-soguanidine. Actinomycin D, although similar to the anthracyclines in having high binding affinity for DNA, is only minimally effective in the same in vitro systems and its direct carcinogenic activity in vivo is moot. These results suggest that satisfactory correlations may be obtainable between tests for tumorigenicity in vivo, and assays for transformation and mutagenesis in vitro, and that adriamycin, and daunomycin may have carcinogenic potential in man.", "contents": "Tumorigenicity in vivo and induction of malignant transformation and mutagenesis in cell cultures by adriamycin and daunomycin. The two anthracycline antitumor antibiotics, adriamycin and daunomycin, have been tested for tumorigenic activity, and the results confirm previous findings that they can induce mammary tumors in female rats receiving single i.v. doses. Both substances are highly potent in producing malignant transformation and mutation in mammalian cell systems in vitro. Their transformming activity is comparable to that of the potent carcinogen, N-methyl-N'-nitro-N-nitro-soguanidine. Actinomycin D, although similar to the anthracyclines in having high binding affinity for DNA, is only minimally effective in the same in vitro systems and its direct carcinogenic activity in vivo is moot. These results suggest that satisfactory correlations may be obtainable between tests for tumorigenicity in vivo, and assays for transformation and mutagenesis in vitro, and that adriamycin, and daunomycin may have carcinogenic potential in man."} {"id": "PMID:1268860", "title": "Nonrandom nature of in vivo methylation of dimethylnitrosamine and the subsequent removal of methylated products from rat liver chromatin DNA.", "content": "This investigation was designed to study whether methylation of liver chromatin DNA by dimethylnitrosamine (DMN) and the subsequent in vivo removal of DNA-bound methylated products are random. Liver chromatin DNA was fractionated into nuclease-digestible and nondigestible material 4 hr following the administration of [3H]DMN (0.5 mg/250 muCi/100 g body weight). Digestion of such methylated liver chromatin with pancreatic DNase I or micrococcal nuclease and analysis of nuclease-digested acid-soluble products revealed a discrepancy between the radioactivity released (72%) and the nucleotides released (50%) as measured by the absorbance at 260 nm. This discrepancy disappeared, and the rate and extent of release of both the radioactivity and the absorbance at 260 nm were identical when the total purified DNA isolated from methylated chromatin was used as the substrate instead of chromatin DNA in the nuclease reaction. These results, together with the fact that guanine contents of the DNA of the two fractions of the chromatin isolated by nuclease digestion were identical, suggest that methylation of the nuclease-accessible region of hepatic chromatin DNA is relatively greater than that of the inaccessible region. The study of the removal of methylated products in the accessible region of the chromatin DNA further reveals that, of the methylated products present at 4 hr, 62% is lost by 3 days, 87% is lost by 1 week and 94% is lost by 2 weeks. However, loss from the nuclease-inaccessible region of chromatin DNA is only 27% by 3 days, 49% by 1 week, and 86% by 2 weeks, thereby suggesting that the removal of methylated products from this region of chromatin DNA is relatively slower compared with that from the nuclease-accessible region of chromatin-DNA. The results of this study thus indicated (a) an increased methylation and faster rate of removal of DMN-induced methylated products in nuclease-accessible regions of chromatin DNA and (b) decreased methylation and slower rate of removal from the nuclease-inaccessible regions of chromatin DNA. It is concluded that the distribution and removal of DMN-induced methylated products in liver chromatin DNA is nonrandom as measured by this technique.", "contents": "Nonrandom nature of in vivo methylation of dimethylnitrosamine and the subsequent removal of methylated products from rat liver chromatin DNA. This investigation was designed to study whether methylation of liver chromatin DNA by dimethylnitrosamine (DMN) and the subsequent in vivo removal of DNA-bound methylated products are random. Liver chromatin DNA was fractionated into nuclease-digestible and nondigestible material 4 hr following the administration of [3H]DMN (0.5 mg/250 muCi/100 g body weight). Digestion of such methylated liver chromatin with pancreatic DNase I or micrococcal nuclease and analysis of nuclease-digested acid-soluble products revealed a discrepancy between the radioactivity released (72%) and the nucleotides released (50%) as measured by the absorbance at 260 nm. This discrepancy disappeared, and the rate and extent of release of both the radioactivity and the absorbance at 260 nm were identical when the total purified DNA isolated from methylated chromatin was used as the substrate instead of chromatin DNA in the nuclease reaction. These results, together with the fact that guanine contents of the DNA of the two fractions of the chromatin isolated by nuclease digestion were identical, suggest that methylation of the nuclease-accessible region of hepatic chromatin DNA is relatively greater than that of the inaccessible region. The study of the removal of methylated products in the accessible region of the chromatin DNA further reveals that, of the methylated products present at 4 hr, 62% is lost by 3 days, 87% is lost by 1 week and 94% is lost by 2 weeks. However, loss from the nuclease-inaccessible region of chromatin DNA is only 27% by 3 days, 49% by 1 week, and 86% by 2 weeks, thereby suggesting that the removal of methylated products from this region of chromatin DNA is relatively slower compared with that from the nuclease-accessible region of chromatin-DNA. The results of this study thus indicated (a) an increased methylation and faster rate of removal of DMN-induced methylated products in nuclease-accessible regions of chromatin DNA and (b) decreased methylation and slower rate of removal from the nuclease-inaccessible regions of chromatin DNA. It is concluded that the distribution and removal of DMN-induced methylated products in liver chromatin DNA is nonrandom as measured by this technique."} {"id": "PMID:1268861", "title": "Evaluation of Papanicolaou smear and effect of sample biopsy in follow-up of cervical dysplasia.", "content": "In a prospective study of women with dysplasia, a superficial sampling biopsy of the cervix was carried out as a periodic check of the cytological findings. The relationship of smear and biopsy results was evaluated, as well as the effect of the biopsy procedure on the subsequent course of dysplasia. We found sufficiently close agreement between smear and biopsy results to conclude that smears and biopsies measure similar aspects of dysplasia. It would appear unwise, however, to rely on Papanicolaou smears exclusively in following women with a history of dysplasia, since negative smears in such women may occasionally show dysplasia in the corresponding biopsy. Periodic corroborative biopsy procedures are therefore indicated in the follow-up care of women with a history of dysplasia. There was no evidence that a superficial sampling biopsy significantly altered the short-term course of dysplasia. There was also no evidence of a cumulative effect of repeated sampling biopsies. These results do not rule out possible effects of other forms of biopsy procedures and schedules on the subsequent course of dysplasia.", "contents": "Evaluation of Papanicolaou smear and effect of sample biopsy in follow-up of cervical dysplasia. In a prospective study of women with dysplasia, a superficial sampling biopsy of the cervix was carried out as a periodic check of the cytological findings. The relationship of smear and biopsy results was evaluated, as well as the effect of the biopsy procedure on the subsequent course of dysplasia. We found sufficiently close agreement between smear and biopsy results to conclude that smears and biopsies measure similar aspects of dysplasia. It would appear unwise, however, to rely on Papanicolaou smears exclusively in following women with a history of dysplasia, since negative smears in such women may occasionally show dysplasia in the corresponding biopsy. Periodic corroborative biopsy procedures are therefore indicated in the follow-up care of women with a history of dysplasia. There was no evidence that a superficial sampling biopsy significantly altered the short-term course of dysplasia. There was also no evidence of a cumulative effect of repeated sampling biopsies. These results do not rule out possible effects of other forms of biopsy procedures and schedules on the subsequent course of dysplasia."} {"id": "PMID:1268862", "title": "Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia.", "content": "Parenteral amygdalin was found to be ineffective in C57BL/6 mice with B16 melanoma and in AKR mice with BW5147 lymphatic leukemia, in doses ranging from 50 to 5000 mg/kg.", "contents": "Failure of amygdalin to arrest B16 melanoma and BW5147 AKR leukemia. Parenteral amygdalin was found to be ineffective in C57BL/6 mice with B16 melanoma and in AKR mice with BW5147 lymphatic leukemia, in doses ranging from 50 to 5000 mg/kg."} {"id": "PMID:1268863", "title": "Differences in cellular uptake and cytofluorescence of adriamycin and N-trifluoroacetyladriamycin-14-valerate.", "content": "Adriamycin-specific fluorescence appears slowly in living cells and is localized in nuclei and chromosomes. N-Trifluoroacetyladriamycin-14-valerate, a recently synthesized adriamycin analog, differs from the parent anthracycline in the rapid appearance of its fluorescence in the cytoplasm of living cells and the lack of any fluorescent binding to nuclei and chromosomes.", "contents": "Differences in cellular uptake and cytofluorescence of adriamycin and N-trifluoroacetyladriamycin-14-valerate. Adriamycin-specific fluorescence appears slowly in living cells and is localized in nuclei and chromosomes. N-Trifluoroacetyladriamycin-14-valerate, a recently synthesized adriamycin analog, differs from the parent anthracycline in the rapid appearance of its fluorescence in the cytoplasm of living cells and the lack of any fluorescent binding to nuclei and chromosomes."} {"id": "PMID:1268864", "title": "Modification of growth of neuroblastoma cells in syngeneic mice by aldehyde-treated neuroblastoma cells.", "content": "Pretreatment of syngeneic strain A mice with aldehyde-fixed neuroblastoma cells (clone NB6R) almost completely protected the mice against challenge with viable NB6R cells. In contrast, tumor growth was enhanced in mice treated with fixed cells after challenge with viable cells.", "contents": "Modification of growth of neuroblastoma cells in syngeneic mice by aldehyde-treated neuroblastoma cells. Pretreatment of syngeneic strain A mice with aldehyde-fixed neuroblastoma cells (clone NB6R) almost completely protected the mice against challenge with viable NB6R cells. In contrast, tumor growth was enhanced in mice treated with fixed cells after challenge with viable cells."} {"id": "PMID:1268865", "title": "Effects of microwave-induced local hyperthermia on mammary adenocarcinoma in C3H mice.", "content": "Microwave-induced hyperthermia was focused locally upon mammary adenocarcinoma implanted in C3H mice when the tumor reached 6 mm in diameter. In 54 treated mice, all tumors diminished in size after the first exposure (43 degrees, 45 min) and disappeared completely following the second treatment. No other effects from heat application were apparent. All the mice in the microwave-treated group survived the whole period of observation (4 months) without any evidence of tumor, while 18 nontreated controls died within 4 weeks after inoculation.", "contents": "Effects of microwave-induced local hyperthermia on mammary adenocarcinoma in C3H mice. Microwave-induced hyperthermia was focused locally upon mammary adenocarcinoma implanted in C3H mice when the tumor reached 6 mm in diameter. In 54 treated mice, all tumors diminished in size after the first exposure (43 degrees, 45 min) and disappeared completely following the second treatment. No other effects from heat application were apparent. All the mice in the microwave-treated group survived the whole period of observation (4 months) without any evidence of tumor, while 18 nontreated controls died within 4 weeks after inoculation."} {"id": "PMID:1268867", "title": "The 13C-N.M.R. spectra of disaccharides of D-glucose, D-galactose, and L-rhamnose as models for immunological polysaccharides.", "content": "Complete assignments of the 13C-n.m.r. spectra of disaccharides having beta-glycosidic linkages are presented and discussed. The disaccharides of D-glucose, D-galactose, L-rhamnose, 2-acetamido-2-deoxy-D-glucose, and 2-acetamido-2-deoxy-D-galactose are model compounds for 13C-n.m.r. studies of immunological polysaccharides. Changing the nature of the reducing glucopyranose rings (D-glucose to L-rhamnose) has no important influence on the chemical shifts of the carbons of the non-reducing glucopyranose ring (D-glucose). The converse is also true: the chemical shifts of the carbons of the reducing glucopyranose ring (L-rhamnose) are not noticeably affected by a change of the non-reducing unit (D-glucose to D-galactose or 2-acetamido-2-deoxy-D-glucose).", "contents": "The 13C-N.M.R. spectra of disaccharides of D-glucose, D-galactose, and L-rhamnose as models for immunological polysaccharides. Complete assignments of the 13C-n.m.r. spectra of disaccharides having beta-glycosidic linkages are presented and discussed. The disaccharides of D-glucose, D-galactose, L-rhamnose, 2-acetamido-2-deoxy-D-glucose, and 2-acetamido-2-deoxy-D-galactose are model compounds for 13C-n.m.r. studies of immunological polysaccharides. Changing the nature of the reducing glucopyranose rings (D-glucose to L-rhamnose) has no important influence on the chemical shifts of the carbons of the non-reducing glucopyranose ring (D-glucose). The converse is also true: the chemical shifts of the carbons of the reducing glucopyranose ring (L-rhamnose) are not noticeably affected by a change of the non-reducing unit (D-glucose to D-galactose or 2-acetamido-2-deoxy-D-glucose)."} {"id": "PMID:1268875", "title": "Synthesis and rearrangements of D-glucosyl esters of aspartic acid linked through the 1- or 4-carboxyl group.", "content": "Catalytic hydrogenation of 2,3,4,6-tetra-O-benzyl-1-O-[1-benzyl N-(benzyloxycarbonyl)-L-aspart-4-oyl]-alpha-D-glucopyranose (1alpha) in acetic acid-2-methoxyethanol gave 1-O-(L-beta-aspartyl)alpha-D-glucopyranose (2alpha) contaminated with 2-O-(L-alpha-aspartyl)-D-glucopyranose (8). Evidence that 8 was formed from the 1-oyl isomer of 1alpha, namely 2,3,4,6-tetra-O-benzyl-1-O-[4-benzyl N-(benzyloxycarbonyl)-L-aspart-1-oyl]-alpha-D-glucopyranose (7alpha), via 1 leads to 2 acyl migration, was obtained by submitting the deprotected D-glucosyl ester to successive N-acetylation, esterification, and O-acetylation; the final product was identified as a approximately 4:1 mixture of 2,3,4,6-tetra-O-acetyl-1-O-[1-methyl N-(acetyl)-L-aspart-4-oyl]-alpha-D-glucopyranose (4alpha) and 1,3,4,6-tetra-O-acetyl-2-O-[4-methyl N-(acetyl)-L-aspart-1-oyl]-D-glucopyranose (6) which were also prepared by definitive methods. On the other hand, deprotection of 1beta gave isomerically pure 2beta which was converted into the peracetylated ester derivative 4beta; an explanation for the differences in aglycon isomeric purity of 2alpha and 2beta is given. Hydrogenolysis of 7beta under the above conditions led to intermolecular transesterification with scission of the C-1 ester bond to give 1-(2-methoxyethyl) L-aspartic acid and D-glucose. Catalytic hydrogenation of 7alpha and 7beta, performed in the presence of trifluoroacetic acid, afforded 1-O-(L-alpha-aspartyl)-alpha- and -beta-D-glucopyranoside trifluoroacetate salts (11alpha and 11beta), respectively. The structure of 11beta was established by successive conversion into 2,3,4,6-tetra-O-acetyl-1-O-[4-methyl N-(acetyl)-L-aspart-1-oyl]-beta-D-glucopyranose (5beta) which was also prepared by definitive methods. Analogous treatment of 11alpha gave the N-acetyl derivative 12 which underwent 1 leads to 2 acyl migration during esterification with diazomethane to give the N-acetyl methyl ester derivative 10; acetylation of 10 afforded 6.", "contents": "Synthesis and rearrangements of D-glucosyl esters of aspartic acid linked through the 1- or 4-carboxyl group. Catalytic hydrogenation of 2,3,4,6-tetra-O-benzyl-1-O-[1-benzyl N-(benzyloxycarbonyl)-L-aspart-4-oyl]-alpha-D-glucopyranose (1alpha) in acetic acid-2-methoxyethanol gave 1-O-(L-beta-aspartyl)alpha-D-glucopyranose (2alpha) contaminated with 2-O-(L-alpha-aspartyl)-D-glucopyranose (8). Evidence that 8 was formed from the 1-oyl isomer of 1alpha, namely 2,3,4,6-tetra-O-benzyl-1-O-[4-benzyl N-(benzyloxycarbonyl)-L-aspart-1-oyl]-alpha-D-glucopyranose (7alpha), via 1 leads to 2 acyl migration, was obtained by submitting the deprotected D-glucosyl ester to successive N-acetylation, esterification, and O-acetylation; the final product was identified as a approximately 4:1 mixture of 2,3,4,6-tetra-O-acetyl-1-O-[1-methyl N-(acetyl)-L-aspart-4-oyl]-alpha-D-glucopyranose (4alpha) and 1,3,4,6-tetra-O-acetyl-2-O-[4-methyl N-(acetyl)-L-aspart-1-oyl]-D-glucopyranose (6) which were also prepared by definitive methods. On the other hand, deprotection of 1beta gave isomerically pure 2beta which was converted into the peracetylated ester derivative 4beta; an explanation for the differences in aglycon isomeric purity of 2alpha and 2beta is given. Hydrogenolysis of 7beta under the above conditions led to intermolecular transesterification with scission of the C-1 ester bond to give 1-(2-methoxyethyl) L-aspartic acid and D-glucose. Catalytic hydrogenation of 7alpha and 7beta, performed in the presence of trifluoroacetic acid, afforded 1-O-(L-alpha-aspartyl)-alpha- and -beta-D-glucopyranoside trifluoroacetate salts (11alpha and 11beta), respectively. The structure of 11beta was established by successive conversion into 2,3,4,6-tetra-O-acetyl-1-O-[4-methyl N-(acetyl)-L-aspart-1-oyl]-beta-D-glucopyranose (5beta) which was also prepared by definitive methods. Analogous treatment of 11alpha gave the N-acetyl derivative 12 which underwent 1 leads to 2 acyl migration during esterification with diazomethane to give the N-acetyl methyl ester derivative 10; acetylation of 10 afforded 6."} {"id": "PMID:1268876", "title": "Synthesis and chemical behaviour of D-glucosyl esters of glutamic acid having the side-chain carboxyl group involved in the glycosidic linkage.", "content": "Simultaneous and stepwise deprotection of the fully benzylated D-glucosyl esters of 1-benzyl N-benzyloxycarbonyl- and N-tert-butyloxycarbonyl-L-glutamic acid (1 and 5, respectively) have been examined. Catalytic hydrogenation of 1 led to intramolecular aminolysis to give pyroglutamic acid and D-glucose, but similar treatment in the presence of trifluoroacetic acid afforded both anomers of 1-O-(L-gamma-glutamyl)-D-glucopyranose, which were characterized as trifluoroacetates (2alpha and 2beta) and converted into 2,3,4,6-tetra-O-acetyl-1-O-[1-methyl N-(acetyl)-L-glutam-5-oyl]-D-glucopyranose (4) which was also prepared by a definitive method. Hydrogenolysis of 5 gave both anomers of 1-O-[N-(tert-butyloxycarbonyl)-L-gamma-glutamyl]-D-glucopyranose (6), which, upon treatment with trifluoroacetic acid at - 10 degrees, afforded 2alpha and 2beta, respectively. The structure of 6beta was established by its conversion into 2,3,4,6-tetra-O-acetyl-1-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-beta-D-glucopyranose (7beta), whereas similar treatment of 6alpha gave a mixture of 1,3,4,6-tetra-O-acetyl-2-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-alpha-D-glucopyranose (9) and 7alpha. A 1 leads to 2 acyl migration occurred during esterification of the aglycon carboxyl group of 6alpha with diazomethane to give 2-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-alpha-D-glucopyranose (8).", "contents": "Synthesis and chemical behaviour of D-glucosyl esters of glutamic acid having the side-chain carboxyl group involved in the glycosidic linkage. Simultaneous and stepwise deprotection of the fully benzylated D-glucosyl esters of 1-benzyl N-benzyloxycarbonyl- and N-tert-butyloxycarbonyl-L-glutamic acid (1 and 5, respectively) have been examined. Catalytic hydrogenation of 1 led to intramolecular aminolysis to give pyroglutamic acid and D-glucose, but similar treatment in the presence of trifluoroacetic acid afforded both anomers of 1-O-(L-gamma-glutamyl)-D-glucopyranose, which were characterized as trifluoroacetates (2alpha and 2beta) and converted into 2,3,4,6-tetra-O-acetyl-1-O-[1-methyl N-(acetyl)-L-glutam-5-oyl]-D-glucopyranose (4) which was also prepared by a definitive method. Hydrogenolysis of 5 gave both anomers of 1-O-[N-(tert-butyloxycarbonyl)-L-gamma-glutamyl]-D-glucopyranose (6), which, upon treatment with trifluoroacetic acid at - 10 degrees, afforded 2alpha and 2beta, respectively. The structure of 6beta was established by its conversion into 2,3,4,6-tetra-O-acetyl-1-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-beta-D-glucopyranose (7beta), whereas similar treatment of 6alpha gave a mixture of 1,3,4,6-tetra-O-acetyl-2-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-alpha-D-glucopyranose (9) and 7alpha. A 1 leads to 2 acyl migration occurred during esterification of the aglycon carboxyl group of 6alpha with diazomethane to give 2-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-alpha-D-glucopyranose (8)."} {"id": "PMID:1268877", "title": "Comb-like derivatives of amylose having (1-6)-linked malto-oligosaccharide side-chains.", "content": "The preparation of acetylated glycosyl bromide derivatives of the higher malto-oligosaccharides was studied by using beta-cyclodextrin or linear malto-oligosaccharides of d.p. 6 and 7. The products were treated with 2,3-di-O-phenylcarbamoyl-6O-tritylamylose in the presence of silver perchlorate (reaction A), and with 2,3-di-O-phenylcarbamoylamylose in the presence of mercuric cyanide and mercuric bromide (reaction B). After removal of the substituents, the branched molecules were characterized by their iodine-binding properties, beta-amylolytic degradation, and their priming activity in phosphorolytic synthesis. The distance between the branch points of the backbone chain was 25-55 and 100-150 units in the products from reactions A and B, respectively. Thus, the frequency of branching was considerably lower than in the comb-like molecules having D-glucose side-chains previously described.", "contents": "Comb-like derivatives of amylose having (1-6)-linked malto-oligosaccharide side-chains. The preparation of acetylated glycosyl bromide derivatives of the higher malto-oligosaccharides was studied by using beta-cyclodextrin or linear malto-oligosaccharides of d.p. 6 and 7. The products were treated with 2,3-di-O-phenylcarbamoyl-6O-tritylamylose in the presence of silver perchlorate (reaction A), and with 2,3-di-O-phenylcarbamoylamylose in the presence of mercuric cyanide and mercuric bromide (reaction B). After removal of the substituents, the branched molecules were characterized by their iodine-binding properties, beta-amylolytic degradation, and their priming activity in phosphorolytic synthesis. The distance between the branch points of the backbone chain was 25-55 and 100-150 units in the products from reactions A and B, respectively. Thus, the frequency of branching was considerably lower than in the comb-like molecules having D-glucose side-chains previously described."} {"id": "PMID:1268878", "title": "Carbohydrate-binding properties of an immobilized alpha-D-galactopyranosyl-binding protein (lectin) from the seeds of Bandeiraea simplicifolia.", "content": "The alpha-D-galactopyranosyl-binding lectin from Bandeiraea simplicifolia has been coupled to cyanogen bromide-activated Sepharose 4B. Using this immobilized system, we have been able to study the interaction of the lectin with model carbohydrate-protein conjugates and polysaccharides, and to reaffirm this protein's carbohydrate-binding specificity. The opportunity for the isolation of biopolymers containing alpha-D-galactopyranosyl end-groups is demonstrated by the single-step purification of a new galactomannan from the seeds of Cassia alata.", "contents": "Carbohydrate-binding properties of an immobilized alpha-D-galactopyranosyl-binding protein (lectin) from the seeds of Bandeiraea simplicifolia. The alpha-D-galactopyranosyl-binding lectin from Bandeiraea simplicifolia has been coupled to cyanogen bromide-activated Sepharose 4B. Using this immobilized system, we have been able to study the interaction of the lectin with model carbohydrate-protein conjugates and polysaccharides, and to reaffirm this protein's carbohydrate-binding specificity. The opportunity for the isolation of biopolymers containing alpha-D-galactopyranosyl end-groups is demonstrated by the single-step purification of a new galactomannan from the seeds of Cassia alata."} {"id": "PMID:1268879", "title": "Studies on the isothermal crystallization of D-glucose and cellulose oligosaccharides by differential scanning calorimetry.", "content": "Isothermal crystallization from the glassy state of D-glucose and cellulose oligosaccharides (e.g., cellobiose, cellotriose, and cellotetraose) has been studied by differential scanning calorimetry. The crystallization of amorphous D-glucose and oligosaccharides was very difficult in the absence of traces of water. Amorphous cellobiose and cellotetraose crystallized far more rapidly than amorphous D-glucose and cellotriose. The activation energy for the crystallization of cellobiose and cellotetraose was approximately 10-12 kJ. mol(-1), while that for D-glucose and cellotriose was approximately 1-2 kJ. mol(-1). An odd-even effect seemed to be associated with the crystallization process of these saccharides.", "contents": "Studies on the isothermal crystallization of D-glucose and cellulose oligosaccharides by differential scanning calorimetry. Isothermal crystallization from the glassy state of D-glucose and cellulose oligosaccharides (e.g., cellobiose, cellotriose, and cellotetraose) has been studied by differential scanning calorimetry. The crystallization of amorphous D-glucose and oligosaccharides was very difficult in the absence of traces of water. Amorphous cellobiose and cellotetraose crystallized far more rapidly than amorphous D-glucose and cellotriose. The activation energy for the crystallization of cellobiose and cellotetraose was approximately 10-12 kJ. mol(-1), while that for D-glucose and cellotriose was approximately 1-2 kJ. mol(-1). An odd-even effect seemed to be associated with the crystallization process of these saccharides."} {"id": "PMID:1268880", "title": "Synthesis and stereochemistry of 6-deoxy-6-halogeno-D-glucofuranose cyclic phosphates.", "content": "1, 2-O-Cyclohexylidene- and 1, 2-O-isopropylidene-alpha-D-glucofuranose react with hexa-alkylphosphorous triamides to give the corresponding 3, 5, 6-phosphites. Treatment of the latter compounds with chlorine and bromine affords 1, 2-substituted 6-deoxy-6-halogeno-alpha-D-glucofuranose 3, 5-phosphorohalogenidates. Replacement of halogen at phsophorus by hydroxyl and amino groups has been investigated. Cyclic phosphorohalogenidates isomerize in N, N-dimethylformamide. The stereochemistry of the compounds investigated was established by using 1H- and 13C-n.m.r. data.", "contents": "Synthesis and stereochemistry of 6-deoxy-6-halogeno-D-glucofuranose cyclic phosphates. 1, 2-O-Cyclohexylidene- and 1, 2-O-isopropylidene-alpha-D-glucofuranose react with hexa-alkylphosphorous triamides to give the corresponding 3, 5, 6-phosphites. Treatment of the latter compounds with chlorine and bromine affords 1, 2-substituted 6-deoxy-6-halogeno-alpha-D-glucofuranose 3, 5-phosphorohalogenidates. Replacement of halogen at phsophorus by hydroxyl and amino groups has been investigated. Cyclic phosphorohalogenidates isomerize in N, N-dimethylformamide. The stereochemistry of the compounds investigated was established by using 1H- and 13C-n.m.r. data."} {"id": "PMID:1268881", "title": "The chemical structure of a fragment of Micrococcus lysodeikticus cell-wall.", "content": "A fragment of Micrococcus lysodeikticus cell-wall obtained by cetylpyridinium recipitation from the nondialyzable portion of the degradation products of egg-white lysozyme was studied by the periodate oxidation and methylation procedures. The fragment consists of a polysaccharide chain composed of about 40 repeating (1 leads to 4)-O-(2-acetamido-2-deoxy-beta-D-mannopyranosyluronic acid)-(1 leads to 6)-O-(alpha-D-glucopyranosyl) residues with D-glucopyranosyl residues at both ends. The alpha-D-glucopyranose residue at the reducing end is linked to a phosphate group that is also linked to C-6 of a 2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucopyranosyl residue of a peptidoglycan chain composed of four repeating (1 leads to 4)-O-[2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucopyranosyl] residues. The peptidoglycan chain has, as nonreducing group, a 2-acetamido-2-deoxy-beta-D-glucopyranosyl group, and, as reducing residue, a 2-acetamido-3-O-(D-1-carboxytheyl)-2-deoxy-beta-D-glucose residue.", "contents": "The chemical structure of a fragment of Micrococcus lysodeikticus cell-wall. A fragment of Micrococcus lysodeikticus cell-wall obtained by cetylpyridinium recipitation from the nondialyzable portion of the degradation products of egg-white lysozyme was studied by the periodate oxidation and methylation procedures. The fragment consists of a polysaccharide chain composed of about 40 repeating (1 leads to 4)-O-(2-acetamido-2-deoxy-beta-D-mannopyranosyluronic acid)-(1 leads to 6)-O-(alpha-D-glucopyranosyl) residues with D-glucopyranosyl residues at both ends. The alpha-D-glucopyranose residue at the reducing end is linked to a phosphate group that is also linked to C-6 of a 2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucopyranosyl residue of a peptidoglycan chain composed of four repeating (1 leads to 4)-O-[2-acetamido-3-O-(D-1-carboxyethyl)-2-deoxy-beta-D-glucopyranosyl] residues. The peptidoglycan chain has, as nonreducing group, a 2-acetamido-2-deoxy-beta-D-glucopyranosyl group, and, as reducing residue, a 2-acetamido-3-O-(D-1-carboxytheyl)-2-deoxy-beta-D-glucose residue."} {"id": "PMID:1268882", "title": "Structural studies of the polysaccharide antigen of Eubacterium saburreum, strain 49.", "content": "The polysaccharide antigen produced by Eubacterium saburreum, strain L 49, is composed of D-glycero-D-galacto-heptose and a new sugar, tentatively identified as 6-deoxy-D-altro-heptose. It contains chains of alternating (1 leads to 3)- and (1 leads to 6)- linked beta-D-glycero-D-galacto-heptopyranosyl residues, the latter being substituted with 6-deoxy-alpha-heptofuranosyl groups at O-3. The polysaccharide further contains 0-acetyl groups, linked to O-7 of part of the heptosyl residues and to O-2 of part of the 6-deoxyheptosyl groups.", "contents": "Structural studies of the polysaccharide antigen of Eubacterium saburreum, strain 49. The polysaccharide antigen produced by Eubacterium saburreum, strain L 49, is composed of D-glycero-D-galacto-heptose and a new sugar, tentatively identified as 6-deoxy-D-altro-heptose. It contains chains of alternating (1 leads to 3)- and (1 leads to 6)- linked beta-D-glycero-D-galacto-heptopyranosyl residues, the latter being substituted with 6-deoxy-alpha-heptofuranosyl groups at O-3. The polysaccharide further contains 0-acetyl groups, linked to O-7 of part of the heptosyl residues and to O-2 of part of the 6-deoxyheptosyl groups."} {"id": "PMID:1268905", "title": "The rodent incisor tooth proliferon.", "content": "The rodent incisor tooth is the site of five cell populations proliferating in harmony: amelocytes, odontocytes, pulp cells, endothelial cells and the periodontal ligament. Their proliferating regions are located in the apex tip, where the various cells originate. Cells displaced from the tooth origin at the apex toward the periphery, mature to perform their specified function. The proliferative events in the tooth are summarized in a conceptual model of the incisor proliferon. The proliferon is an oriented structure with an origin and periphery. It consists of four basic elements: parenchyma, connective tissue, blood vessels and nerve fibres, all interacting continuously. All four are indispensable in the definition of the proliferon.", "contents": "The rodent incisor tooth proliferon. The rodent incisor tooth is the site of five cell populations proliferating in harmony: amelocytes, odontocytes, pulp cells, endothelial cells and the periodontal ligament. Their proliferating regions are located in the apex tip, where the various cells originate. Cells displaced from the tooth origin at the apex toward the periphery, mature to perform their specified function. The proliferative events in the tooth are summarized in a conceptual model of the incisor proliferon. The proliferon is an oriented structure with an origin and periphery. It consists of four basic elements: parenchyma, connective tissue, blood vessels and nerve fibres, all interacting continuously. All four are indispensable in the definition of the proliferon."} {"id": "PMID:1268906", "title": "DNA turnover and thymidine re-utilization in mouse tissues.", "content": "Mice were injected intravenously with tritiated thymidine (TdR) and 125I-labeled iododeoxyuridine (IUdR) in low doses to provide a simultaneous labeling of tissue DNA with non-toxic amounts of these two precursors. The total activity per organ and the ratio of the two isotopes was measured in the DNA at various times between 1 and 15 days after the injection. Since TdR from dying cells is re-utilized more effeciently than IUdR from the same cells, more labeled TdR than IUdR was retained in the tissue DNA in these experiments. From the slopes of the regression lines, the true rated of turnover of replicating tissue DNA and the per cent re-utilization of TdR were calculated. Re-utilization of TdR varied from 37 to 60% in the six tissues examined.", "contents": "DNA turnover and thymidine re-utilization in mouse tissues. Mice were injected intravenously with tritiated thymidine (TdR) and 125I-labeled iododeoxyuridine (IUdR) in low doses to provide a simultaneous labeling of tissue DNA with non-toxic amounts of these two precursors. The total activity per organ and the ratio of the two isotopes was measured in the DNA at various times between 1 and 15 days after the injection. Since TdR from dying cells is re-utilized more effeciently than IUdR from the same cells, more labeled TdR than IUdR was retained in the tissue DNA in these experiments. From the slopes of the regression lines, the true rated of turnover of replicating tissue DNA and the per cent re-utilization of TdR were calculated. Re-utilization of TdR varied from 37 to 60% in the six tissues examined."} {"id": "PMID:1268907", "title": "The migration of lymphocytes across specialized vascular endothelium. I. The entry of lymphocytes into the isolated mesenteric lymph-node of the rat.", "content": "The chain of lymph-nodes in the rat mesentery was isolated and the preparation was perfused via cannulae in the superior mesenteric vessels. The perfusate consisted of serum to which labelled lymphocytes had usually been added. The entry of radioactively labelled lymphocytes from the blood vessels into the lymph-nodes was studied by scintillation counting and autoradiography. It was observed that: (1) In the perfused node labelled lymphocytes localized in and around post-capillary venules in the paracortex as they do early after i.v. injection. (2) The number of lymphocytes which entered the node was directly proportional to the concentration in the perfusate over the range studied. The proportion of cells retained in the node varied considerably around a mean of 11% of lymphocytes reaching it. (3) The isolated lymph-node released few if any lymphocytes into the effluent (venous) perfusate. (4) Large lymphocytes migrated into isolated lymph-nodes slightly more readliy than did small lymphocytes. (5) Unlike intact cells isolated lymphocyte membranes did not adhere to specialized vascular endothelium.", "contents": "The migration of lymphocytes across specialized vascular endothelium. I. The entry of lymphocytes into the isolated mesenteric lymph-node of the rat. The chain of lymph-nodes in the rat mesentery was isolated and the preparation was perfused via cannulae in the superior mesenteric vessels. The perfusate consisted of serum to which labelled lymphocytes had usually been added. The entry of radioactively labelled lymphocytes from the blood vessels into the lymph-nodes was studied by scintillation counting and autoradiography. It was observed that: (1) In the perfused node labelled lymphocytes localized in and around post-capillary venules in the paracortex as they do early after i.v. injection. (2) The number of lymphocytes which entered the node was directly proportional to the concentration in the perfusate over the range studied. The proportion of cells retained in the node varied considerably around a mean of 11% of lymphocytes reaching it. (3) The isolated lymph-node released few if any lymphocytes into the effluent (venous) perfusate. (4) Large lymphocytes migrated into isolated lymph-nodes slightly more readliy than did small lymphocytes. (5) Unlike intact cells isolated lymphocyte membranes did not adhere to specialized vascular endothelium."} {"id": "PMID:1268908", "title": "A two emulsion autoradiographic technique and the discrimination of the three different types of labelling after double labelling with 3H- and 14C-thymidine.", "content": "The first part of the paper deals with a two emulsion autoradiographic technique for double labelling experiments with 3H- and 14C-thymidine which permits a clear discrimination of the different types of labelling. In the second part the application of this technique to cell kinetic studies is discussed. Accurate discrimination between the different types of labelling, namely purely 3H-, purely 14C- and double (3H + 14C) labelling, is only possible if the activity ratio of 3H- to 14C-thymidine is sufficiently high. This condition is necessary for a reliable distinction between those grains in the first emulsion which are due to true 3H-labelling and spurious grains which are simultaneously produced in the same emulsion by 14C-beta-particles. Experiments are described to determine the required activity ratio of 3H- to 14C-thymidine.", "contents": "A two emulsion autoradiographic technique and the discrimination of the three different types of labelling after double labelling with 3H- and 14C-thymidine. The first part of the paper deals with a two emulsion autoradiographic technique for double labelling experiments with 3H- and 14C-thymidine which permits a clear discrimination of the different types of labelling. In the second part the application of this technique to cell kinetic studies is discussed. Accurate discrimination between the different types of labelling, namely purely 3H-, purely 14C- and double (3H + 14C) labelling, is only possible if the activity ratio of 3H- to 14C-thymidine is sufficiently high. This condition is necessary for a reliable distinction between those grains in the first emulsion which are due to true 3H-labelling and spurious grains which are simultaneously produced in the same emulsion by 14C-beta-particles. Experiments are described to determine the required activity ratio of 3H- to 14C-thymidine."} {"id": "PMID:1268909", "title": "Study of the effect of hydroxyurea on the erythropoietin-sensitive cells.", "content": "The response of polycythaemic mice to a standard dose of erythropoietin has been measured at various time intervals after single or repeated injections of hydroxyurea. The results exclude S phase of the cell cycle as the period responsive to erythropoietin. They suggest the existence of feedback mechanisms within the cell cycle, operating at the G1--S boundary and within the G1 phase. Hydroxyurea given to polycythaemic mice at various time intervals after erythropoietin induced characteristic changes in the response. These changes can be explained if both gradual transit of differentiated cells into the DNA synthesis (S phase) and changes in amount of the erythropoietin sensitive cells caused by the feedback mechanisms operating in the cell cycle are considered.", "contents": "Study of the effect of hydroxyurea on the erythropoietin-sensitive cells. The response of polycythaemic mice to a standard dose of erythropoietin has been measured at various time intervals after single or repeated injections of hydroxyurea. The results exclude S phase of the cell cycle as the period responsive to erythropoietin. They suggest the existence of feedback mechanisms within the cell cycle, operating at the G1--S boundary and within the G1 phase. Hydroxyurea given to polycythaemic mice at various time intervals after erythropoietin induced characteristic changes in the response. These changes can be explained if both gradual transit of differentiated cells into the DNA synthesis (S phase) and changes in amount of the erythropoietin sensitive cells caused by the feedback mechanisms operating in the cell cycle are considered."} {"id": "PMID:1268910", "title": "Changes in liver cells ploidy of young rats following isoprenaline treatment.", "content": "Cell proliferation induced by isoprenaline (IPR) stimulation in very high doses was assayed in the liver of young rats, and the formation of polyploid cells was studied form the 15th to the 70th day of life. A general stimulatory effect on a complex process of cellular multiplication, leading to a population of tetraploid cells, was found to be accelerated; the earlier appearance of binucleate cells and the subsequent significant variations in their incidence confirmed the role of this cell type as an intermediate step in the process of polyploidization. Evidence was found of concomitant size changes of the hepatocytes, which might be partially independent of the effect of DNA content. The stimulation was no longer evident 20--30 days from the end of treatment, by when the cells which had come into contact with IPR should have completed the whole sequence of events leading to the formation of tetraploid mononucleate cells.", "contents": "Changes in liver cells ploidy of young rats following isoprenaline treatment. Cell proliferation induced by isoprenaline (IPR) stimulation in very high doses was assayed in the liver of young rats, and the formation of polyploid cells was studied form the 15th to the 70th day of life. A general stimulatory effect on a complex process of cellular multiplication, leading to a population of tetraploid cells, was found to be accelerated; the earlier appearance of binucleate cells and the subsequent significant variations in their incidence confirmed the role of this cell type as an intermediate step in the process of polyploidization. Evidence was found of concomitant size changes of the hepatocytes, which might be partially independent of the effect of DNA content. The stimulation was no longer evident 20--30 days from the end of treatment, by when the cells which had come into contact with IPR should have completed the whole sequence of events leading to the formation of tetraploid mononucleate cells."} {"id": "PMID:1268911", "title": "Periodontal ligament cell kinetics following orthodontic tooth movement.", "content": "The population of periodontal ligament (PDL) fibroblasts examined in this study may include osteogenic progenitor cells. PDL fibroblast and osteoblast kinetics in the periodontal ligament of the rat were measured following orthodontic stimulation of bone formation. Both single and multiple injections of tritiated thymidine (3H-TdR) were used. In single injection experiments, the peak percentage of PDL fibroblasts labeled with 3H-TdR is 15% at 22 hr post-stimulation. In multiple injection experiments, the total percentage of fibroblasts in the PDL which respond by synthesizing DNA is 50%. 3H-TdR-labeled osteoblasts appear at the same rate as, but with a time delay after, the labeled fibroblasts. Following stimulation, the most likely source of osteoblasts at the bbone forming site is not only fibroblasts which make DNA, divide, then differentiate, but also fibroblasts which either are differentiated to osteoblasts without DNA synthesis and cell division, or are released from G2 block by the orthodontic stimulation.", "contents": "Periodontal ligament cell kinetics following orthodontic tooth movement. The population of periodontal ligament (PDL) fibroblasts examined in this study may include osteogenic progenitor cells. PDL fibroblast and osteoblast kinetics in the periodontal ligament of the rat were measured following orthodontic stimulation of bone formation. Both single and multiple injections of tritiated thymidine (3H-TdR) were used. In single injection experiments, the peak percentage of PDL fibroblasts labeled with 3H-TdR is 15% at 22 hr post-stimulation. In multiple injection experiments, the total percentage of fibroblasts in the PDL which respond by synthesizing DNA is 50%. 3H-TdR-labeled osteoblasts appear at the same rate as, but with a time delay after, the labeled fibroblasts. Following stimulation, the most likely source of osteoblasts at the bbone forming site is not only fibroblasts which make DNA, divide, then differentiate, but also fibroblasts which either are differentiated to osteoblasts without DNA synthesis and cell division, or are released from G2 block by the orthodontic stimulation."} {"id": "PMID:1268912", "title": "The extravascular channel system in the rostral pituitary of Mugil cephalus (Teleostei) as revealed by use of horseradish peroxidase.", "content": "The interlobular spaces, separating the neuro- and the adenohypophysis can be visualized in the pituitary of the Grey Mullet by using the horseradish peroxidase technique. On the one hand, these spaces communicate with the pericapillary spaces. On the other, they are linked with the pericellular spaces in the adenohypophysis and the periaxonal spaces in the neurohypophysis, thus providing a pathway for the exchange of metabolites and hormones between blood system, epithelial cells and the terminal region of the neurosecretory axons. The interlobular spaces branch off between the tips of the corticotrop cells and form a network adjacent to the adeno- and neurohypophyseal interface. It is possible that branches of this network penetrate into the interior of the corticotrops. The probable role of the network is to permit close contact between neurosecretory hormones and the corticotrops and also to enable the corticotrop hormone to reach the capillaries.", "contents": "The extravascular channel system in the rostral pituitary of Mugil cephalus (Teleostei) as revealed by use of horseradish peroxidase. The interlobular spaces, separating the neuro- and the adenohypophysis can be visualized in the pituitary of the Grey Mullet by using the horseradish peroxidase technique. On the one hand, these spaces communicate with the pericapillary spaces. On the other, they are linked with the pericellular spaces in the adenohypophysis and the periaxonal spaces in the neurohypophysis, thus providing a pathway for the exchange of metabolites and hormones between blood system, epithelial cells and the terminal region of the neurosecretory axons. The interlobular spaces branch off between the tips of the corticotrop cells and form a network adjacent to the adeno- and neurohypophyseal interface. It is possible that branches of this network penetrate into the interior of the corticotrops. The probable role of the network is to permit close contact between neurosecretory hormones and the corticotrops and also to enable the corticotrop hormone to reach the capillaries."} {"id": "PMID:1268913", "title": "Comparative ultrastructural investigations of the pineal organ of the blind cave fish, Anoptichthys jordani, and its ancestor, the eyed river fish, Astyanax mexicanus.", "content": "A comparative ultrastructural study has been made of the pineal organ in specimens of two closely related populations of the characid fish, Astyanaz mexicanus. The specimens of one population are living in the river, under natural light conditions. The specimens of the other population, originally described as Anoptichthys jordani, are living in a completely dark cave. In specimens of both populations the pineal organ consists of a spindle shaped end-vesicle, connected to the diencephalic roof by a slender stalk. The pineal tissue is compact and consists predominantly of glia-like supporting cells and sensory cells resembling the photoreceptor cells of the lateral vertebrate eye. Phagocytotic microglia-like cells can be found in close contact with the outer segments of the sensory cells. Nerve cells are located in the neighbourhood of neuropil formations, in which synaptic contacts are established between sensory cells and nerve cells. From these nerve cells fibers are emerging, forming the pineal tract that runs down the pineal stalk towards the diencephalon. On the basis of the ultrastructure described by other authors it is concluded that the pineal organ in specimens of the river population of Astyanax mexicanus resembles the pineal organ of other fish species. In specimens of the river population, reared under normal light-dark conditions for 3, 9 or 18 months, conspicuous morphological changes have not been detected in the presumably light-sensitive outer segments of the sensory cells or in other parts of the pineal tissue. In specimens of the cave populations, reared under identical conditions, an age-dependent, gradual regression of the regular outer segment organization of the pineal sensory cells takes place. In other parts of the pineal tissue, only small morphological changes can be observed. In specimens of the cave population, reared in constant darkness, the regression of the pineal outer segment organization begins earlier and is obvious. It is postulated that the gradual age-dependent regression of the regular organization of the outer segments in the pineal organ of cave specimens of Astyanax mexicanus is genetically determined and indicates a regressive evolution of the pineal light sensitivity. The expression of the regressive traits is dependent on the environmental light conditions.", "contents": "Comparative ultrastructural investigations of the pineal organ of the blind cave fish, Anoptichthys jordani, and its ancestor, the eyed river fish, Astyanax mexicanus. A comparative ultrastructural study has been made of the pineal organ in specimens of two closely related populations of the characid fish, Astyanaz mexicanus. The specimens of one population are living in the river, under natural light conditions. The specimens of the other population, originally described as Anoptichthys jordani, are living in a completely dark cave. In specimens of both populations the pineal organ consists of a spindle shaped end-vesicle, connected to the diencephalic roof by a slender stalk. The pineal tissue is compact and consists predominantly of glia-like supporting cells and sensory cells resembling the photoreceptor cells of the lateral vertebrate eye. Phagocytotic microglia-like cells can be found in close contact with the outer segments of the sensory cells. Nerve cells are located in the neighbourhood of neuropil formations, in which synaptic contacts are established between sensory cells and nerve cells. From these nerve cells fibers are emerging, forming the pineal tract that runs down the pineal stalk towards the diencephalon. On the basis of the ultrastructure described by other authors it is concluded that the pineal organ in specimens of the river population of Astyanax mexicanus resembles the pineal organ of other fish species. In specimens of the river population, reared under normal light-dark conditions for 3, 9 or 18 months, conspicuous morphological changes have not been detected in the presumably light-sensitive outer segments of the sensory cells or in other parts of the pineal tissue. In specimens of the cave populations, reared under identical conditions, an age-dependent, gradual regression of the regular outer segment organization of the pineal sensory cells takes place. In other parts of the pineal tissue, only small morphological changes can be observed. In specimens of the cave population, reared in constant darkness, the regression of the pineal outer segment organization begins earlier and is obvious. It is postulated that the gradual age-dependent regression of the regular organization of the outer segments in the pineal organ of cave specimens of Astyanax mexicanus is genetically determined and indicates a regressive evolution of the pineal light sensitivity. The expression of the regressive traits is dependent on the environmental light conditions."} {"id": "PMID:1268914", "title": "On the fine structure of the regressing ecdysial glands of carcinus maenas L. (Crustacea Decapoda) parasitized by Sacculina carcini Thompson.", "content": "The ecdysial glands (Y organs) of the crab Carcinus maenas regress in the presence of an external parasite, Sacculina carcini. This regression is more or less severe and may lead to complete autolysis. Three gradual stages in this involutionary process are described. In stage I, the gland cells are nearly normal. Nuclei and cytoplasmic organelles remain unchanged, but large vacuoles begin to appear. Stage II corresponds to more or less drastic nuclear pyknosis and cytoplasmic alterations. Myelin figures are large and numerous. Lysosomes and autophagic vacuoles with phosphatase activity are abundant. However, the general cellular architecture remains preserved. Stage III corresponds to irreversible cytolysis; nuclear envelopes and plasma membranes have disappeared. What remains is an accumulation of cellular debris becoming engulfed by circulating hemocytes. Not all of the gland cells of any given Y organ show the same degree of regression; degeneration is asynchronous. Structures seemingly corresponding to absorptive roots of the parasite are seen. Their lumen is coated with microvilli. The putative direct and indirect influences of the rhizocephalan parasite on its host are discussed. Our results on regressing Y organs of parasitized crabs are compared with those on regressing ecdysial glands of insects.", "contents": "On the fine structure of the regressing ecdysial glands of carcinus maenas L. (Crustacea Decapoda) parasitized by Sacculina carcini Thompson. The ecdysial glands (Y organs) of the crab Carcinus maenas regress in the presence of an external parasite, Sacculina carcini. This regression is more or less severe and may lead to complete autolysis. Three gradual stages in this involutionary process are described. In stage I, the gland cells are nearly normal. Nuclei and cytoplasmic organelles remain unchanged, but large vacuoles begin to appear. Stage II corresponds to more or less drastic nuclear pyknosis and cytoplasmic alterations. Myelin figures are large and numerous. Lysosomes and autophagic vacuoles with phosphatase activity are abundant. However, the general cellular architecture remains preserved. Stage III corresponds to irreversible cytolysis; nuclear envelopes and plasma membranes have disappeared. What remains is an accumulation of cellular debris becoming engulfed by circulating hemocytes. Not all of the gland cells of any given Y organ show the same degree of regression; degeneration is asynchronous. Structures seemingly corresponding to absorptive roots of the parasite are seen. Their lumen is coated with microvilli. The putative direct and indirect influences of the rhizocephalan parasite on its host are discussed. Our results on regressing Y organs of parasitized crabs are compared with those on regressing ecdysial glands of insects."} {"id": "PMID:1268915", "title": "The morphological categorization of developing synaptic junctions.", "content": "The molecular layer of rat occipital cortex was studied at a number of ages throughout postnatal development in an attempt to a formulate a quantitative morphogenetic scheme of synaptic development. As previous work had pointed to the potential usefulness of E-PTA stained material in synaptogenic studies, this technique was employed. Synaptic junctions were assigned to five categories, A-E, on the basis of variations in the organization of their presynaptic densities. Of these categories, Type A represented a mature junctional form with well-defined and discrete dense projections. Type E, by contrast, represented the immature end of the spectrum, its presynaptic apposition generally lacking recognizable densities. Types B-D represented intermediate forms. As development proceeded, the percentage of A type junctions increased from 0.3% at 7 days to 25% in the adult. Type E junctions showed the opposite trend falling from 42% at 7 days to 5% in the adult. On the basis of these results, and those relating to types B-D, possible morphogenetic schemes involving the five synaptic categories are put forward. These schemes incorporate and extend those previously suggested by other workers. By placing observations on a quantitative footing, the schemes proposed here lend themselves to use in experimental investigations.", "contents": "The morphological categorization of developing synaptic junctions. The molecular layer of rat occipital cortex was studied at a number of ages throughout postnatal development in an attempt to a formulate a quantitative morphogenetic scheme of synaptic development. As previous work had pointed to the potential usefulness of E-PTA stained material in synaptogenic studies, this technique was employed. Synaptic junctions were assigned to five categories, A-E, on the basis of variations in the organization of their presynaptic densities. Of these categories, Type A represented a mature junctional form with well-defined and discrete dense projections. Type E, by contrast, represented the immature end of the spectrum, its presynaptic apposition generally lacking recognizable densities. Types B-D represented intermediate forms. As development proceeded, the percentage of A type junctions increased from 0.3% at 7 days to 25% in the adult. Type E junctions showed the opposite trend falling from 42% at 7 days to 5% in the adult. On the basis of these results, and those relating to types B-D, possible morphogenetic schemes involving the five synaptic categories are put forward. These schemes incorporate and extend those previously suggested by other workers. By placing observations on a quantitative footing, the schemes proposed here lend themselves to use in experimental investigations."} {"id": "PMID:1268916", "title": "Arterio-venous anastomoses in rainbow trout gill filaments: a scanning and transmission electron microscopic study.", "content": "The origin of arterio-venous anastomoses, connecting the efferent filament artery (EFA) with the central venous sinus (CVS) of gill filaments can be well discerned by scanning electron microscopy in the rainbow trout. Corresponding vessels between the afferent filament artery and the CVS could not be detected with the techniques applied. AVA-specific endothelial cells are characterized by their bulky shape and their microvillous surface. The general morphology of AVA's in Salmo gairdneri is very similar to that of AVA's in Tilapia mossambica (Vogel et al., 1974) but they are much longer in the trout. No filament whorls have been encountered in AVA endothelia of Salmo gairdneri.", "contents": "Arterio-venous anastomoses in rainbow trout gill filaments: a scanning and transmission electron microscopic study. The origin of arterio-venous anastomoses, connecting the efferent filament artery (EFA) with the central venous sinus (CVS) of gill filaments can be well discerned by scanning electron microscopy in the rainbow trout. Corresponding vessels between the afferent filament artery and the CVS could not be detected with the techniques applied. AVA-specific endothelial cells are characterized by their bulky shape and their microvillous surface. The general morphology of AVA's in Salmo gairdneri is very similar to that of AVA's in Tilapia mossambica (Vogel et al., 1974) but they are much longer in the trout. No filament whorls have been encountered in AVA endothelia of Salmo gairdneri."} {"id": "PMID:1268917", "title": "Histological and ultrastructural studies of the rabbit pars intermedia in organ culture. II. Developing tissue.", "content": "Pars intermedia (PI) tissue from fetal, perinatal, neonatal and juvenile rabbits has been maintained in organ culture for up to nine weeks after explantation. Autoradiography showed that DNA synthesis took place for at least 22 days of culturing. PI-glandular cells and interstitial cells remain identifiable throughout this period but ACT-type cells were recognised only up to six weeks. Material from fetal and perinatal animals had a higher proportion of surviving cells than that from adult animals. The degree of differentiation achieved by PI-glandular cells in vitro appears to depend on three factors: i) the stage of development reached before explantation; ii) the original topographic position in the PI tissue before explantation; and iii) the position in the explant in relation to the gas-liquid interphase.", "contents": "Histological and ultrastructural studies of the rabbit pars intermedia in organ culture. II. Developing tissue. Pars intermedia (PI) tissue from fetal, perinatal, neonatal and juvenile rabbits has been maintained in organ culture for up to nine weeks after explantation. Autoradiography showed that DNA synthesis took place for at least 22 days of culturing. PI-glandular cells and interstitial cells remain identifiable throughout this period but ACT-type cells were recognised only up to six weeks. Material from fetal and perinatal animals had a higher proportion of surviving cells than that from adult animals. The degree of differentiation achieved by PI-glandular cells in vitro appears to depend on three factors: i) the stage of development reached before explantation; ii) the original topographic position in the PI tissue before explantation; and iii) the position in the explant in relation to the gas-liquid interphase."} {"id": "PMID:1268918", "title": "Nucleolar DNA in oocytes of Salmo irideus (Gibbons).", "content": "The amplification of ribosomal genes has been studied in oocytes from Salmo irideus. In situ nucleic acid hybridization showed that the synthesis of nucleolar DNA begins in oogonium and proceeds slowly through leptotene and zygotene when a small amount of extrachromosomal nucleolar DNA is produced. In early pachytene there is a rapid build-up of nucleolar DNA demonstrable by rapid incorporation of tritiated thymidine. Synthesis stops completely in early diplotene when nucleolar DNA becomes dispersed over the inner surface of the nuclear envelope in the form of small Feulgen-positive granules. Photometric measurements of Feulgen stained nuclei showed that the final amount of amplified nucleolar DNA synthesized in each oocyte is approximately 20 mug. The amplified DNA does not form a heterochromatic mass. The buoyant density of the amplified nucleolar DNA calculated from analytical centrifuge tracings in relation to DNA from Micrococcus luteus (rho = 1.731 g cm-3) is 1.715 g cm-3 and corresponds to a G+C content of 57%. There are indications that the buoyant density of the somatic nucleolar DNA is lower than that of amplified nucleolar DNA. Similarities and differences between ribosomal gene amplifications in oocytes of Salmo irideus and the corresponding process in Xenopus are discussed.", "contents": "Nucleolar DNA in oocytes of Salmo irideus (Gibbons). The amplification of ribosomal genes has been studied in oocytes from Salmo irideus. In situ nucleic acid hybridization showed that the synthesis of nucleolar DNA begins in oogonium and proceeds slowly through leptotene and zygotene when a small amount of extrachromosomal nucleolar DNA is produced. In early pachytene there is a rapid build-up of nucleolar DNA demonstrable by rapid incorporation of tritiated thymidine. Synthesis stops completely in early diplotene when nucleolar DNA becomes dispersed over the inner surface of the nuclear envelope in the form of small Feulgen-positive granules. Photometric measurements of Feulgen stained nuclei showed that the final amount of amplified nucleolar DNA synthesized in each oocyte is approximately 20 mug. The amplified DNA does not form a heterochromatic mass. The buoyant density of the amplified nucleolar DNA calculated from analytical centrifuge tracings in relation to DNA from Micrococcus luteus (rho = 1.731 g cm-3) is 1.715 g cm-3 and corresponds to a G+C content of 57%. There are indications that the buoyant density of the somatic nucleolar DNA is lower than that of amplified nucleolar DNA. Similarities and differences between ribosomal gene amplifications in oocytes of Salmo irideus and the corresponding process in Xenopus are discussed."} {"id": "PMID:1268919", "title": "Surface morphology of lens fibers from eyes of normal and microphthalmic (Browman) rats.", "content": "The surface features of cortical fibers from lenses of normal adult rats and microphthalmic rats of the Browman strain have been studied by scanning electron microscopy. In the normal lenses, superficial cortical fibers follow a straight course from inner to outer pole whereas the deeper cortical fibers, while straight near the poles, pursue an undulating or zig-zag course at and near the equator. Almost all of the fibers are hexagonal in cross section and all fibers throughout their entire length are bound by interdigitating processes at each corner of the hexagon to corners of two adjacent fibers. Some fibers are also affixed by a single row of ball and socket junctions located on their broad outer and inner surfaces. Lens fibers from Browman rats display both minor and major abnormalities. These included segmentation, formation of incisures and lateral protrusions, corrugation and villous-like alteration of the broad fiber surface and development of parallel ridges of broad surfaces in a basket-weave pattern.", "contents": "Surface morphology of lens fibers from eyes of normal and microphthalmic (Browman) rats. The surface features of cortical fibers from lenses of normal adult rats and microphthalmic rats of the Browman strain have been studied by scanning electron microscopy. In the normal lenses, superficial cortical fibers follow a straight course from inner to outer pole whereas the deeper cortical fibers, while straight near the poles, pursue an undulating or zig-zag course at and near the equator. Almost all of the fibers are hexagonal in cross section and all fibers throughout their entire length are bound by interdigitating processes at each corner of the hexagon to corners of two adjacent fibers. Some fibers are also affixed by a single row of ball and socket junctions located on their broad outer and inner surfaces. Lens fibers from Browman rats display both minor and major abnormalities. These included segmentation, formation of incisures and lateral protrusions, corrugation and villous-like alteration of the broad fiber surface and development of parallel ridges of broad surfaces in a basket-weave pattern."} {"id": "PMID:1268920", "title": "Ultrastructure of the new neuromuscular junctions formed during reinnervation of rat soleus muscle by a \"foreign\" nerve.", "content": "In rats the \"fast\" fibular nerve was transposed to the \"slow\" soleus muscle outside the original innervation band. Formation of new neuromuscular junctions was induced by cutting the soleus nerve after different periods of time. The morphological maturation of these junctions was studied by electron microscopy. New neuromuscular junctions do not form when the original innervation is left intact. Three to five days after denervation, vesicle-laden terminal boutons contact muscle fibers with only the basal lamina of the latter intervening. Three weeks after denervation, most boutons are larger and postsynaptic folds are present, although younger stages are also seen. Sixteen weeks after denervation, the neuromuscular junctions appear mature. This corresponds well with electrophysiological findings in the same material. The fully developed neuromuscular junctions sixteen weeks after denervation possess postsynaptic folds similar to those of normal \"fast\" muscle fibers. This suggests that the \"fast\" fibular nerve rather than the \"slow\" soleus muscle fibers determines the morphology of the postsynaptic folds. Possible trophic neuromuscular interactions are discussed.", "contents": "Ultrastructure of the new neuromuscular junctions formed during reinnervation of rat soleus muscle by a \"foreign\" nerve. In rats the \"fast\" fibular nerve was transposed to the \"slow\" soleus muscle outside the original innervation band. Formation of new neuromuscular junctions was induced by cutting the soleus nerve after different periods of time. The morphological maturation of these junctions was studied by electron microscopy. New neuromuscular junctions do not form when the original innervation is left intact. Three to five days after denervation, vesicle-laden terminal boutons contact muscle fibers with only the basal lamina of the latter intervening. Three weeks after denervation, most boutons are larger and postsynaptic folds are present, although younger stages are also seen. Sixteen weeks after denervation, the neuromuscular junctions appear mature. This corresponds well with electrophysiological findings in the same material. The fully developed neuromuscular junctions sixteen weeks after denervation possess postsynaptic folds similar to those of normal \"fast\" muscle fibers. This suggests that the \"fast\" fibular nerve rather than the \"slow\" soleus muscle fibers determines the morphology of the postsynaptic folds. Possible trophic neuromuscular interactions are discussed."} {"id": "PMID:1268921", "title": "Immunohistochemical localization of LH-producing cells in the adenohypophysis of the Japanese quail, Coturnix coturnix japonica.", "content": "The cells that produce luteinizing hormone (LH) in the adenohypophysis of the Japanese quail were identified immunohistochemically using anti-chicken LH serum and horseradish peroxidase-labeled goat anti-rabbit gamma globulin serum. The LH cells are localized in the caudal lobe of the pars distalis. They are elongate in shape shape and are polarized toward the sinusoids, especially in their active states. Alterations in size of LH cells are directly related to changes in circulating LH levels as induced by castration or photostimulation. The LH cells identified immunohistochemically were only stained by alcian blue with periodic acid-Schiff (PAS), alcian blue and orange G. PAS-positive gonadotropic cells in the cephalic lobe were stained immunohistochemically only slightly if at all using anti-chicken LH serum and consequently may be FSH producing cells. In the cephalic lobe another type of basophilic cell was stained with alcian blue. These cells were also stained immunohistochemically with anti-chicken LH serum. These cells may possibly be identified as TSH cells due to the characteristics of the anti-chicken LH serum used in this study which cross react with LH and TSH but only slightly with FSH, and also on the basis of previous light and electron microscopic studies.", "contents": "Immunohistochemical localization of LH-producing cells in the adenohypophysis of the Japanese quail, Coturnix coturnix japonica. The cells that produce luteinizing hormone (LH) in the adenohypophysis of the Japanese quail were identified immunohistochemically using anti-chicken LH serum and horseradish peroxidase-labeled goat anti-rabbit gamma globulin serum. The LH cells are localized in the caudal lobe of the pars distalis. They are elongate in shape shape and are polarized toward the sinusoids, especially in their active states. Alterations in size of LH cells are directly related to changes in circulating LH levels as induced by castration or photostimulation. The LH cells identified immunohistochemically were only stained by alcian blue with periodic acid-Schiff (PAS), alcian blue and orange G. PAS-positive gonadotropic cells in the cephalic lobe were stained immunohistochemically only slightly if at all using anti-chicken LH serum and consequently may be FSH producing cells. In the cephalic lobe another type of basophilic cell was stained with alcian blue. These cells were also stained immunohistochemically with anti-chicken LH serum. These cells may possibly be identified as TSH cells due to the characteristics of the anti-chicken LH serum used in this study which cross react with LH and TSH but only slightly with FSH, and also on the basis of previous light and electron microscopic studies."} {"id": "PMID:1268922", "title": "The effects of testosterone, 5alpha-dihydrotestosterone, 3alpha-androstanediol, and 3beta-androstanediol on epithelial fine structure of the rabbit epididymis in organ culture.", "content": "The fine structure of the corpus epididymidis of the rabbit has been studied following organ culture. Various modifications of tissue preparation and culture conditions were examined to obtain good maintenance of cellular integrity as well as to preserve sperm fertilizing ability. After 5 to 7 days in culture in the absence of hormonal support, the epididymal epithelium showed signs indicative of cellular regression. Such changes included shrinkage of the cells, loss of the border of stereocilia, decrease in smooth endoplasmic reticulum, and an increase in autophagic vacuoles. The presence of androgens in culture media prevented cellular regression to varying degrees, depending on the hormone utilized. With regard to maintenance of cellular integrity, potency of the androgens tested was as follows: 5alpha-dihydrotestosterone greater than or equal to 3alpha-androstanediol greater than testosterone greater than 3beta-androstanediol. Addition of insulin to dihydrotestosterone-containing cultures resulted in no improvement in maintenance. Phagocytosis of spermatozoa by epithelial cells was observed in cultured tubules and the degree of spermiophagy was inversely proportional to successful maintenance of fine structural characteristics of epithelial cells. The morphological findings reported here correlate well with the fertilizing ability of spermatozoa from cultured epididymis as reported in an accompanying communication.", "contents": "The effects of testosterone, 5alpha-dihydrotestosterone, 3alpha-androstanediol, and 3beta-androstanediol on epithelial fine structure of the rabbit epididymis in organ culture. The fine structure of the corpus epididymidis of the rabbit has been studied following organ culture. Various modifications of tissue preparation and culture conditions were examined to obtain good maintenance of cellular integrity as well as to preserve sperm fertilizing ability. After 5 to 7 days in culture in the absence of hormonal support, the epididymal epithelium showed signs indicative of cellular regression. Such changes included shrinkage of the cells, loss of the border of stereocilia, decrease in smooth endoplasmic reticulum, and an increase in autophagic vacuoles. The presence of androgens in culture media prevented cellular regression to varying degrees, depending on the hormone utilized. With regard to maintenance of cellular integrity, potency of the androgens tested was as follows: 5alpha-dihydrotestosterone greater than or equal to 3alpha-androstanediol greater than testosterone greater than 3beta-androstanediol. Addition of insulin to dihydrotestosterone-containing cultures resulted in no improvement in maintenance. Phagocytosis of spermatozoa by epithelial cells was observed in cultured tubules and the degree of spermiophagy was inversely proportional to successful maintenance of fine structural characteristics of epithelial cells. The morphological findings reported here correlate well with the fertilizing ability of spermatozoa from cultured epididymis as reported in an accompanying communication."} {"id": "PMID:1268923", "title": "The effects of testosterone, 5alpha-dihydrotestosterone, 3alpha-androstanediol, and 3beta-androstanediol on the maturation of rabbit epididymal spermatozoa in organ culture.", "content": "The fertilizing ability of spermatozoa from epididymal tubules maintained in organ cultures from 1 to 7 days was assessed after artificial insemination into receptive does. It was found that spermatozoa from the distal corpus which were already capable of fertilizing eggs prior to the cultures retain this ability for 1 day without addition of hormone and for 3-4 days when testosterone (0.5 mug/ml) or 5alpha-dihydrotestosterone (0.5 mug/ml) is added to the culture medium. Spermatozoa from the proximal corpus which were not capable of fertilizing eggs prior to the cultures remain so after 1 day in cultures without addition of hormone. Testosterone, 5alpha-dihydrotesterone, 3alpha-androstanediol, or 3beta-androstanediol was added to cultures of proximal corpus at a concentration of 0.5 mug/ml. Only with 5alpha-DHT is the mean percentage of fertilization significantly higher than the percentage obtained without addition of hormone. Insulin does not potentiate the effect of 5alpha-DHT on sperm fertilizing ability. Epithelial growth factor is ineffective. Spermatozoa from the caput epididymidis kept in cultures for 1 to 4 days remain infertile. The results are discussed in light of the morphological findings presented in the preceding communication and in relation to the physiological requirement for sperm maturation in the epididymis.", "contents": "The effects of testosterone, 5alpha-dihydrotestosterone, 3alpha-androstanediol, and 3beta-androstanediol on the maturation of rabbit epididymal spermatozoa in organ culture. The fertilizing ability of spermatozoa from epididymal tubules maintained in organ cultures from 1 to 7 days was assessed after artificial insemination into receptive does. It was found that spermatozoa from the distal corpus which were already capable of fertilizing eggs prior to the cultures retain this ability for 1 day without addition of hormone and for 3-4 days when testosterone (0.5 mug/ml) or 5alpha-dihydrotestosterone (0.5 mug/ml) is added to the culture medium. Spermatozoa from the proximal corpus which were not capable of fertilizing eggs prior to the cultures remain so after 1 day in cultures without addition of hormone. Testosterone, 5alpha-dihydrotesterone, 3alpha-androstanediol, or 3beta-androstanediol was added to cultures of proximal corpus at a concentration of 0.5 mug/ml. Only with 5alpha-DHT is the mean percentage of fertilization significantly higher than the percentage obtained without addition of hormone. Insulin does not potentiate the effect of 5alpha-DHT on sperm fertilizing ability. Epithelial growth factor is ineffective. Spermatozoa from the caput epididymidis kept in cultures for 1 to 4 days remain infertile. The results are discussed in light of the morphological findings presented in the preceding communication and in relation to the physiological requirement for sperm maturation in the epididymis."} {"id": "PMID:1268924", "title": "Studies on the innervation of the endometrium.", "content": "The innervation of the endometrium of rabbit, rat, mink, mongoose and pig has been investigated electron microscopically. Large bundles of nerve fibers can be observed in the connective tissue spaces within the basal layer of the endometrium. Unmyelinated nerve fibers enter the lamina functionalis, terminal nerve fibers penetrate the basal lamina and make contact with the glandular and the cavum epithelial cells. The terminal axons contain abundant synaptic vesicles, dense core vesicles and mitochondria. To date, no specialized presynaptic or postsynaptic membranes have been found.", "contents": "Studies on the innervation of the endometrium. The innervation of the endometrium of rabbit, rat, mink, mongoose and pig has been investigated electron microscopically. Large bundles of nerve fibers can be observed in the connective tissue spaces within the basal layer of the endometrium. Unmyelinated nerve fibers enter the lamina functionalis, terminal nerve fibers penetrate the basal lamina and make contact with the glandular and the cavum epithelial cells. The terminal axons contain abundant synaptic vesicles, dense core vesicles and mitochondria. To date, no specialized presynaptic or postsynaptic membranes have been found."} {"id": "PMID:1268925", "title": "High voltage electron microscopy of the optic neuropile of the housefly, Musca domestica.", "content": "Synaptic cartridges of the first optic neuropile (lamina ganglionaris) of the housefly were examined by high voltage electron microscopy (HVEM). Stereo pairs (from thick, i.e., 0.25 mum, sections viewed at 1,000 kV) provided a three dimensional representation of cartridge neurons and clearly revealed the lateral spread, bifurcation and some functional associations of Type I (L1, L2) monopolar interneurons. Slightly proximal to cartridge neck level, pairs of retinular (R) axons made contact with each other and it appeared that R processes projected through the cleft between the Type I interneurons. No junctional modifications were seen between contiguous R axon terminals. The speculation was made that functional contact might exist between neighboring R axons prior to their extensive synapses with principal first order interneurons. Such alleged coupling between R axons would account for several electrophysiological findings from other laboratories. Modifications in EM technique applicable for HVEM were detailed. The value of obtaining thick serial sections and the use of the HVEM in expediting three dimensional reconstructions of neuropile were demonstrated.", "contents": "High voltage electron microscopy of the optic neuropile of the housefly, Musca domestica. Synaptic cartridges of the first optic neuropile (lamina ganglionaris) of the housefly were examined by high voltage electron microscopy (HVEM). Stereo pairs (from thick, i.e., 0.25 mum, sections viewed at 1,000 kV) provided a three dimensional representation of cartridge neurons and clearly revealed the lateral spread, bifurcation and some functional associations of Type I (L1, L2) monopolar interneurons. Slightly proximal to cartridge neck level, pairs of retinular (R) axons made contact with each other and it appeared that R processes projected through the cleft between the Type I interneurons. No junctional modifications were seen between contiguous R axon terminals. The speculation was made that functional contact might exist between neighboring R axons prior to their extensive synapses with principal first order interneurons. Such alleged coupling between R axons would account for several electrophysiological findings from other laboratories. Modifications in EM technique applicable for HVEM were detailed. The value of obtaining thick serial sections and the use of the HVEM in expediting three dimensional reconstructions of neuropile were demonstrated."} {"id": "PMID:1268926", "title": "Retinohypothalamic projection in the mouse: electron microscopic and iontophoretic investigations of hypothalamic and optic centers.", "content": "The problem of the direct retinohypothalamic projection in mammals (Moore, 1973) was reinvestigated in the laboratory mouse by electron microscopy and cobalt chloride-iontophoresis. The time-course of the axonal degeneration in the suprachiasmatic nucleus was studied 3, 6 and 12 h, 1, 2, 4, 6, 9 and 12 days after unilateral retinectomy. Specificity of the degenerative changes was controlled by investigation of the superficial layers of the superior colliculus. The ratio of crossed to uncrossed optic fibers could could be determined by counting degenerating structures (axons and terminals) in the optic chiasma and the ipsilateral and contralateral areas of the optic tract, the suprachiasmatic nucleus, and the superior colliculus. The number of degenerating axons in the suprachiasmatic nucleus showed a maximum one day after unilateral retinectomy and was, at all stages studied, two to three times higher in the contralateral than in the ipsilateral nuclear area. In the optic tract and in the superior colliculus the number of degenerating profiles was three times higher in the contralateral than in the ipsilateral area. Retinohypothalamic connections and crossing pattern of retinal fibers were studied light microscopically using impregnation with cobalt sulfide in whole mounts of brains. Most of the optic fibers in the laboratory mouse are crossed crossed (70-80%). A bundle of predominantly crossed optic fibers runs to the suprachiasmatic nucleus.", "contents": "Retinohypothalamic projection in the mouse: electron microscopic and iontophoretic investigations of hypothalamic and optic centers. The problem of the direct retinohypothalamic projection in mammals (Moore, 1973) was reinvestigated in the laboratory mouse by electron microscopy and cobalt chloride-iontophoresis. The time-course of the axonal degeneration in the suprachiasmatic nucleus was studied 3, 6 and 12 h, 1, 2, 4, 6, 9 and 12 days after unilateral retinectomy. Specificity of the degenerative changes was controlled by investigation of the superficial layers of the superior colliculus. The ratio of crossed to uncrossed optic fibers could could be determined by counting degenerating structures (axons and terminals) in the optic chiasma and the ipsilateral and contralateral areas of the optic tract, the suprachiasmatic nucleus, and the superior colliculus. The number of degenerating axons in the suprachiasmatic nucleus showed a maximum one day after unilateral retinectomy and was, at all stages studied, two to three times higher in the contralateral than in the ipsilateral nuclear area. In the optic tract and in the superior colliculus the number of degenerating profiles was three times higher in the contralateral than in the ipsilateral area. Retinohypothalamic connections and crossing pattern of retinal fibers were studied light microscopically using impregnation with cobalt sulfide in whole mounts of brains. Most of the optic fibers in the laboratory mouse are crossed crossed (70-80%). A bundle of predominantly crossed optic fibers runs to the suprachiasmatic nucleus."} {"id": "PMID:1268927", "title": "Microtubule--synaptic vesicle associations in cultured rat spinal cord neurons.", "content": "This paper describes new ultrastructural features of neural processes and of synapses in cultured CNS tissue treated with albumin before fixation using a modification of the technique recently introduced by Gray (1975). Nerve fibre bundles in explants of foetal spinal cord grown in vitro for 15-18 days were transected microsurgically. After transection the cultures were exposed to 20% albumin in distilled water and then fixed in unbuffered osmium tetroxide followed by unbuffered glutaraldehyde. In this material, but not in controls (injured but not exposed to albumin; exposed to albumin without injury) microtubules were found within many axonal varicosities, often situated close to presynaptic membrane specializations. These microtubules were closely associated with vesicles resembling synaptic vesicles, which were occasionally aligned in rows along the microtubules. Similar vesicle-microtubule associations were also found in non-terminal axons. Microtubules were also observed very close to some postsynaptic densities. The possiblity that the microtubule-vesicle associations are involved in vesicle movements (along axons and/or within axon terminals) is discussed. A more direct involvement of microtubules in terminals in the mechanism of transmitter release is also considered.", "contents": "Microtubule--synaptic vesicle associations in cultured rat spinal cord neurons. This paper describes new ultrastructural features of neural processes and of synapses in cultured CNS tissue treated with albumin before fixation using a modification of the technique recently introduced by Gray (1975). Nerve fibre bundles in explants of foetal spinal cord grown in vitro for 15-18 days were transected microsurgically. After transection the cultures were exposed to 20% albumin in distilled water and then fixed in unbuffered osmium tetroxide followed by unbuffered glutaraldehyde. In this material, but not in controls (injured but not exposed to albumin; exposed to albumin without injury) microtubules were found within many axonal varicosities, often situated close to presynaptic membrane specializations. These microtubules were closely associated with vesicles resembling synaptic vesicles, which were occasionally aligned in rows along the microtubules. Similar vesicle-microtubule associations were also found in non-terminal axons. Microtubules were also observed very close to some postsynaptic densities. The possiblity that the microtubule-vesicle associations are involved in vesicle movements (along axons and/or within axon terminals) is discussed. A more direct involvement of microtubules in terminals in the mechanism of transmitter release is also considered."} {"id": "PMID:1268928", "title": "Ultrastructural studies on the secretory process in the epithelioid cells of the juxtaglomerular apparatus.", "content": "The epithelioid cells of the juxtaglomerular apparatus have been studied with respect to the release mechanism of the secretory granules. Invaginations of the plasma membrane into the interior of the epithelioid cells are interpreted as stages before or after an exocytotic process. Granules are sometimes observed in close contact with the plasma membrane, and material with electron density similar to that of the granules can also be observed in the invaginations. These morphological features suggest that the granular material of the epithelioid cells is extruded into the texture of the basal lamina. Furthermore, a dense network of microtubules and microfilaments is described and the functional role of this system in exocytosis is discussed.", "contents": "Ultrastructural studies on the secretory process in the epithelioid cells of the juxtaglomerular apparatus. The epithelioid cells of the juxtaglomerular apparatus have been studied with respect to the release mechanism of the secretory granules. Invaginations of the plasma membrane into the interior of the epithelioid cells are interpreted as stages before or after an exocytotic process. Granules are sometimes observed in close contact with the plasma membrane, and material with electron density similar to that of the granules can also be observed in the invaginations. These morphological features suggest that the granular material of the epithelioid cells is extruded into the texture of the basal lamina. Furthermore, a dense network of microtubules and microfilaments is described and the functional role of this system in exocytosis is discussed."} {"id": "PMID:1268929", "title": "Fine structure of chemosensitive cells (glomus caroticum) in tissue culture.", "content": "Cells of the carotid body of both embryonic and 1 to 2-d-old rabbits were cultured in monolayer in primary tissue culture. The cells grew in their original association of type I and type II cells. The fine structure of both cell types was similar to that in vivo. Even after one week in culture their morphological characteristics, such as the dense-cored vesicles, were preserved. The prolonged synthesis of catecholamines in culture and the formation of new granular vesicles is discussed.", "contents": "Fine structure of chemosensitive cells (glomus caroticum) in tissue culture. Cells of the carotid body of both embryonic and 1 to 2-d-old rabbits were cultured in monolayer in primary tissue culture. The cells grew in their original association of type I and type II cells. The fine structure of both cell types was similar to that in vivo. Even after one week in culture their morphological characteristics, such as the dense-cored vesicles, were preserved. The prolonged synthesis of catecholamines in culture and the formation of new granular vesicles is discussed."} {"id": "PMID:1268930", "title": "Export of protein from the osteoclast as studied by electron microscopic autoradiography.", "content": "The present electron microscopic autoradiographic study includes a quantitative analysis of osteoclasts in vitro using tritiated leucin as a protein tracer. A significant increase in the grain density over the ruffled border and the underlying resportion zone was demonstrated two hours post pulse whereas the grain density of the remaining cytoplasm was relatively constant. This indicates a transport of newly synthesized protein from the osteoclast to the extracellular resorption zone. Earlier histochemical and biochemical experiments suggest that the exported protein may represent lysosomal enzymes to be used in the extracellular bone degradation.", "contents": "Export of protein from the osteoclast as studied by electron microscopic autoradiography. The present electron microscopic autoradiographic study includes a quantitative analysis of osteoclasts in vitro using tritiated leucin as a protein tracer. A significant increase in the grain density over the ruffled border and the underlying resportion zone was demonstrated two hours post pulse whereas the grain density of the remaining cytoplasm was relatively constant. This indicates a transport of newly synthesized protein from the osteoclast to the extracellular resorption zone. Earlier histochemical and biochemical experiments suggest that the exported protein may represent lysosomal enzymes to be used in the extracellular bone degradation."} {"id": "PMID:1268931", "title": "Freeze-fracture study of the junctional complexes of human and rabbit thyroid follicles.", "content": "Zonulae occludentes, gap junctions and desmosomes have been demonstrated in replicas of freeze-fractured follicular cells of normal human and rabbit thyroid glands. The zonulae occludentes between the human follicular cells are composed of two to eight strands, which completely separate the intercellular space from the follicular lumen. Four to twelve or more strands are visible between the follicular cells of the rabbit thyroid gland. In the meshes of the zonulae occludentes as well as below them, gap junctions are present. They are numerous on the fracture faces of the human follicular cell membranes, but infrequent in those of the rabbit. Aggregates of particles related to desomosomes are found in the deeper meshes of the zonulae occludentes or close to them.", "contents": "Freeze-fracture study of the junctional complexes of human and rabbit thyroid follicles. Zonulae occludentes, gap junctions and desmosomes have been demonstrated in replicas of freeze-fractured follicular cells of normal human and rabbit thyroid glands. The zonulae occludentes between the human follicular cells are composed of two to eight strands, which completely separate the intercellular space from the follicular lumen. Four to twelve or more strands are visible between the follicular cells of the rabbit thyroid gland. In the meshes of the zonulae occludentes as well as below them, gap junctions are present. They are numerous on the fracture faces of the human follicular cell membranes, but infrequent in those of the rabbit. Aggregates of particles related to desomosomes are found in the deeper meshes of the zonulae occludentes or close to them."} {"id": "PMID:1268932", "title": "Identification, in the external region of the rat median eminence, of separate neurophysin-vasopressin and neurophysin-oxytocin containing nerve fibres.", "content": "Immuno-enzyme cytochemical investigations, using single and double staining techniques, showed that the external region of the rat median eminence contains separate neurophysin-vasopressin fibres and neurophysin-oxytocin fibres. These neurophysin-hormone containing nerve fibres are influenced by bilateral adrenalectomy and by colchicine treatment. The external region of the median eminence of the homozygous Brattleboro rat contains neurophysin-oxytocin fibres. It does not contain immuno-reactive neurophysin-vasopressin fibres. Bilateral adrenalectomy also influences the neurophysin-vasopressin containing neurons of the suprachiasmatic nuclei. In the neurons of the parvicellular part of the rat hypothalamic paraventricular nuclei, staining for vasopressin and for oxytocin is completely absent.", "contents": "Identification, in the external region of the rat median eminence, of separate neurophysin-vasopressin and neurophysin-oxytocin containing nerve fibres. Immuno-enzyme cytochemical investigations, using single and double staining techniques, showed that the external region of the rat median eminence contains separate neurophysin-vasopressin fibres and neurophysin-oxytocin fibres. These neurophysin-hormone containing nerve fibres are influenced by bilateral adrenalectomy and by colchicine treatment. The external region of the median eminence of the homozygous Brattleboro rat contains neurophysin-oxytocin fibres. It does not contain immuno-reactive neurophysin-vasopressin fibres. Bilateral adrenalectomy also influences the neurophysin-vasopressin containing neurons of the suprachiasmatic nuclei. In the neurons of the parvicellular part of the rat hypothalamic paraventricular nuclei, staining for vasopressin and for oxytocin is completely absent."} {"id": "PMID:1268933", "title": "Immunohistochemical localization of prolactin cells of the pars distalis in the fetal and neonatal hamster: a light and electron microscopy study.", "content": "Using the immunoperoxidase technique, a small number of prolactin cells were first detected in the pars distalis of the hamster near developing sinusoids at 13 1/2 days gestation. Little change in number or distribution of immunoreactive cells was noted until the first few days after birth when a dramatic increase in number of immunoreactive cells was demonstrated throughout the pars distalis. Electron microscopy revealed cells in the fetal and neonatal anterior pituitary which had immunoreactive granules smaller in diameter than those seen in adult pituitary cells.", "contents": "Immunohistochemical localization of prolactin cells of the pars distalis in the fetal and neonatal hamster: a light and electron microscopy study. Using the immunoperoxidase technique, a small number of prolactin cells were first detected in the pars distalis of the hamster near developing sinusoids at 13 1/2 days gestation. Little change in number or distribution of immunoreactive cells was noted until the first few days after birth when a dramatic increase in number of immunoreactive cells was demonstrated throughout the pars distalis. Electron microscopy revealed cells in the fetal and neonatal anterior pituitary which had immunoreactive granules smaller in diameter than those seen in adult pituitary cells."} {"id": "PMID:1268934", "title": "Ultrastructure of the aortic diverticula of the adult dragonfly Sympetrum danae (Odonata: Anisoptera).", "content": "The aorta of Sympetrum danae possesses two dorsal diverticula: one in the mesothorax and one in the metathorax. They are very similar in form and position. Each diverticulum has a dorsal valve through which blood is pumped from the wings down into the aorta. The wall of the aortic diverticula consists of two simple cell layers: an outer epidermis-like layer and an inner muscle layer. The nuclei of the muscle cells are situated close to the lumen of the diverticula. The mitochondria are evenly dispersed between the myofibrils and are often paired up on either side of the Z-band. The Z-bands are thick and fragmented. The length of the sarcomeres varies from 3.3 to 6.1 mu. The A-band length is about 3 mu. The myofibrils consist of thick (250 A) and thin (85 A) filaments. Each thick filament is surrounded by 9-12 thin filaments. The sarcoplasmic reticulum is well developed and separates the myofibrils with one or two layers. The T-tubules are flattened and branch irregularly like a two-dimensional tree between the lamellar myofibrils. Intercalated discs are observed. The peculiarities of the muscle of aortic diverticula in S. danae are discussed in relation to various muscles of other insects and arthropods.", "contents": "Ultrastructure of the aortic diverticula of the adult dragonfly Sympetrum danae (Odonata: Anisoptera). The aorta of Sympetrum danae possesses two dorsal diverticula: one in the mesothorax and one in the metathorax. They are very similar in form and position. Each diverticulum has a dorsal valve through which blood is pumped from the wings down into the aorta. The wall of the aortic diverticula consists of two simple cell layers: an outer epidermis-like layer and an inner muscle layer. The nuclei of the muscle cells are situated close to the lumen of the diverticula. The mitochondria are evenly dispersed between the myofibrils and are often paired up on either side of the Z-band. The Z-bands are thick and fragmented. The length of the sarcomeres varies from 3.3 to 6.1 mu. The A-band length is about 3 mu. The myofibrils consist of thick (250 A) and thin (85 A) filaments. Each thick filament is surrounded by 9-12 thin filaments. The sarcoplasmic reticulum is well developed and separates the myofibrils with one or two layers. The T-tubules are flattened and branch irregularly like a two-dimensional tree between the lamellar myofibrils. Intercalated discs are observed. The peculiarities of the muscle of aortic diverticula in S. danae are discussed in relation to various muscles of other insects and arthropods."} {"id": "PMID:1268935", "title": "The ocellus of the cockroach, Periplaneta americana (Blattariae): receptory area.", "content": "The ocelli of Periplaneta americana were studied by light and electron microscopy. The view that the ocellus of the cockroach represents a degenerated structure can no longer be supported. All organelles necessary for function are present. The club-shaped retinular cells lie homogeneously distributed in the cupule of the ocellus. Rhabdoms are seen as sickle-, y-, x- or star-shaped structures with up to six cells in formation. Cells were found which had formed two rhabdomeres. The mass of cell organelles lies in the cytoplasm between the cell nucleus and the rhabdom. Smooth endoplasmic reticulum is wound into a spindle formation of considerable size at the origin of the axon in some cells. A cylindrical body in which 10-40 microtubules are packed, as yet unknown in insect retinular cells, is described. The receptory area of the ocellus terminates in a tapetum which contains granules, soluble in alcohol. The axon bundles of the retinular cells run through the tapetum and immediately thereafter make synaptic contact with dendrites of the ocellar nerve cells, while still within the ocellus.", "contents": "The ocellus of the cockroach, Periplaneta americana (Blattariae): receptory area. The ocelli of Periplaneta americana were studied by light and electron microscopy. The view that the ocellus of the cockroach represents a degenerated structure can no longer be supported. All organelles necessary for function are present. The club-shaped retinular cells lie homogeneously distributed in the cupule of the ocellus. Rhabdoms are seen as sickle-, y-, x- or star-shaped structures with up to six cells in formation. Cells were found which had formed two rhabdomeres. The mass of cell organelles lies in the cytoplasm between the cell nucleus and the rhabdom. Smooth endoplasmic reticulum is wound into a spindle formation of considerable size at the origin of the axon in some cells. A cylindrical body in which 10-40 microtubules are packed, as yet unknown in insect retinular cells, is described. The receptory area of the ocellus terminates in a tapetum which contains granules, soluble in alcohol. The axon bundles of the retinular cells run through the tapetum and immediately thereafter make synaptic contact with dendrites of the ocellar nerve cells, while still within the ocellus."} {"id": "PMID:1268936", "title": "Light and electron microscopic studies on the pars intermedia of the chameleon.", "content": "The neurointermediate lobe of the hypophysis in the Chameleon (Chamaeleo dilepis) was examined with light and electron microscopic methods, with special reference to the cytology of the pars intermedia (PI). The PI is the largest lobe of the hypophysis consisting of (1) dark cells with secretory granules ranging from 200-600 nm; (2) light cells, far fewer in number, containing granules 150-300 nm in diameter; (3) stellate, non-secretory cells. The secretory cells abut onto the perivascular basal lamina of the capillary sinusoids while their apical part borders an intercellular space. This surface of the cells often bears a cilium. The granules arise from the Golgi cisternae while small detached vesicles are found between circumscribed sites of the cell membrane and the Golgi apparatus. No nervous elements were found in the pars intermedia and it is assumed that the regulation of this lobe is purely humoral. This is supported by the presence of three types of nerve terminals in the pars nervosa: (a) terminals with large secretory granules and small vesicles; (b) terminals with dense-core vesicles and small vesicles; (c) terminals with small vesicles only. All of these are secretory as indicated by the presence of the synaptic semidesmosomes formed with the perivascular basal lamina.", "contents": "Light and electron microscopic studies on the pars intermedia of the chameleon. The neurointermediate lobe of the hypophysis in the Chameleon (Chamaeleo dilepis) was examined with light and electron microscopic methods, with special reference to the cytology of the pars intermedia (PI). The PI is the largest lobe of the hypophysis consisting of (1) dark cells with secretory granules ranging from 200-600 nm; (2) light cells, far fewer in number, containing granules 150-300 nm in diameter; (3) stellate, non-secretory cells. The secretory cells abut onto the perivascular basal lamina of the capillary sinusoids while their apical part borders an intercellular space. This surface of the cells often bears a cilium. The granules arise from the Golgi cisternae while small detached vesicles are found between circumscribed sites of the cell membrane and the Golgi apparatus. No nervous elements were found in the pars intermedia and it is assumed that the regulation of this lobe is purely humoral. This is supported by the presence of three types of nerve terminals in the pars nervosa: (a) terminals with large secretory granules and small vesicles; (b) terminals with dense-core vesicles and small vesicles; (c) terminals with small vesicles only. All of these are secretory as indicated by the presence of the synaptic semidesmosomes formed with the perivascular basal lamina."} {"id": "PMID:1268937", "title": "Ultrastructural features of adult human tendon.", "content": "A variety of human tendons have been studied at the electron microscope level. The fibers of these tendons are composed of collagen fibrils that average 1,750 A and 600 A in diameter. A third population that measures 100 A in diameter may represent immature collagen or filaments that are incorporated into tendon elastic fibers. The larger collagen fibrils vary in ratio with respect to one another, and are connected by interfibrillar bridges which in some cases appear to extend through the substance of the fibril. The collagen fibrils of the paratenon are less-well organized than those of the tendon proper and average 600 A in diameter. Tendons that exhibit the property of lateral stretch (plantaris and palmaris) were compared at the ultrastructural level with tendons that do not have this property. No differences between the two tendon types could be determined in normal or spread preparations, indicating that the differences in physical characteristics are a result of fiber rather than fibril organization.", "contents": "Ultrastructural features of adult human tendon. A variety of human tendons have been studied at the electron microscope level. The fibers of these tendons are composed of collagen fibrils that average 1,750 A and 600 A in diameter. A third population that measures 100 A in diameter may represent immature collagen or filaments that are incorporated into tendon elastic fibers. The larger collagen fibrils vary in ratio with respect to one another, and are connected by interfibrillar bridges which in some cases appear to extend through the substance of the fibril. The collagen fibrils of the paratenon are less-well organized than those of the tendon proper and average 600 A in diameter. Tendons that exhibit the property of lateral stretch (plantaris and palmaris) were compared at the ultrastructural level with tendons that do not have this property. No differences between the two tendon types could be determined in normal or spread preparations, indicating that the differences in physical characteristics are a result of fiber rather than fibril organization."} {"id": "PMID:1268938", "title": "Electron microscopic study on the gel of the central part of the corpus vitreum in the ox.", "content": "The central part of the corpus vitreum in the ox possesses a relative firmness. Electron microscopically it has been shown to consist of collagen fibrils with interfibrillar spaces containing 8 nm thick granules. The granules are made up of chains of macromolecules (hyaluronic acid in an oligomer state) 130-200 nm in length and of an oval shape. The collagen fibrils are tightly covered with 8.5 nm thick macromolecules which represent highly polymerized hyaluronic acid. These macromolecules can be stained with ruthenium-red.", "contents": "Electron microscopic study on the gel of the central part of the corpus vitreum in the ox. The central part of the corpus vitreum in the ox possesses a relative firmness. Electron microscopically it has been shown to consist of collagen fibrils with interfibrillar spaces containing 8 nm thick granules. The granules are made up of chains of macromolecules (hyaluronic acid in an oligomer state) 130-200 nm in length and of an oval shape. The collagen fibrils are tightly covered with 8.5 nm thick macromolecules which represent highly polymerized hyaluronic acid. These macromolecules can be stained with ruthenium-red."} {"id": "PMID:1269043", "title": "Arapen: a secondary complex between platinum ethylenediamine dichloride and cytosine arabinoside. I. Preparations and reactivity towards nucleic acid constituents.", "content": "An equimolecular complex between platinum ethylenediamine dichloride (PtenCl2) and 1-beta-D-arabinofuranosyl cytosine (araC) has been prepared (arapen). This 1 : 1 complex in which both ethylenediamine and araC moieties carried a radioactive label was found to be unreactive towards cytosine and guanine derivatives, but to react to the extent of 30% with deoxyadenosine, adenosine 5' -monophosphate, polyadenylic acid, poly a(AT) and DNA at comparable rates. It is suggested that adenine compounds react with platinum complexes such as PtenCl2 in a bidentate manner, but are still able to react with arapen as monodentate ligands. However, hydrolysis of the last chloride ion from arapen may not be complete, and the incoming adenine nucleophile is only able to react to a limited extent.", "contents": "Arapen: a secondary complex between platinum ethylenediamine dichloride and cytosine arabinoside. I. Preparations and reactivity towards nucleic acid constituents. An equimolecular complex between platinum ethylenediamine dichloride (PtenCl2) and 1-beta-D-arabinofuranosyl cytosine (araC) has been prepared (arapen). This 1 : 1 complex in which both ethylenediamine and araC moieties carried a radioactive label was found to be unreactive towards cytosine and guanine derivatives, but to react to the extent of 30% with deoxyadenosine, adenosine 5' -monophosphate, polyadenylic acid, poly a(AT) and DNA at comparable rates. It is suggested that adenine compounds react with platinum complexes such as PtenCl2 in a bidentate manner, but are still able to react with arapen as monodentate ligands. However, hydrolysis of the last chloride ion from arapen may not be complete, and the incoming adenine nucleophile is only able to react to a limited extent."} {"id": "PMID:1269044", "title": "Transfer of methyl groups from N-dimethylnitrosamine to glycerolipids in rat liver.", "content": "We have examined the in vivo labeling of lipids after a single intraperitoneal injection of the carcinogen, (C14) dimethylnitrosamine, into rats. Liver was most active in incorporating (C14) methyl groups into lipids (0.91% of the injected dose) and 80% of the activity appeared in sn-3-phosphatidyl-choline. Chromatographic analysis of the products (and derivatives) formed after treatment of the (C14) phosphatidylcholine with phospholipase A2 (EC 3.1.1.4) and phospholipase C (EC 3.1.4.3) demonstrated that 89% of the radioactivity was in the choline moiety. These results indicate the transfer of methyl groups to lipids occurred via the lipid methylation pathway that converts phosphatidylethanolamine to phosphatidylcholine.", "contents": "Transfer of methyl groups from N-dimethylnitrosamine to glycerolipids in rat liver. We have examined the in vivo labeling of lipids after a single intraperitoneal injection of the carcinogen, (C14) dimethylnitrosamine, into rats. Liver was most active in incorporating (C14) methyl groups into lipids (0.91% of the injected dose) and 80% of the activity appeared in sn-3-phosphatidyl-choline. Chromatographic analysis of the products (and derivatives) formed after treatment of the (C14) phosphatidylcholine with phospholipase A2 (EC 3.1.1.4) and phospholipase C (EC 3.1.4.3) demonstrated that 89% of the radioactivity was in the choline moiety. These results indicate the transfer of methyl groups to lipids occurred via the lipid methylation pathway that converts phosphatidylethanolamine to phosphatidylcholine."} {"id": "PMID:1269045", "title": "The binding of dehydroheliotridine to DNA and the effect of it and other compounds on repair synthesis in main and satellite band DNA.", "content": "This study was aimed at elucidating the mechanisms of the preferential depression of satellite DNA synthesis by dehydroheliotridine (DHH). DHH was found to induce repair synthesis to the same extent in both main and satellite band DNA in cultured sheep lymphocytes. This was also the case with acridine orange, nitrogen mustard (HN2) and ethyl methane-sulphonate (EMS). Using analytical equilibrium ultracentrifugation no difference was found between the extents of in vitro binding of DHH by main and satellite band DNA. From these results it was concluded that the depression of the synthesis of satellite DNA could not be explained by either its preferential binding of DHH or by less effective repair mechanisms. Radiolabelled DHH when added to synchronized cultures of ovine kidney cells was found to be preferentially bound to the satellite DNA (one DHH molecule to 6000 nucleotides) compared with the main band DNA (one to 10 000). When 5-bromodeoxyuridine (BUdR) was added to the cultures no DHH label was found in the heavy, semiconservatively replicated DNA band. From these findings it is suggested that attack may occur during mitosis where all of the satellite DNA may be undergoing synthesis at the same time, thus explaining the increased amount of DHH bound to the satellite.", "contents": "The binding of dehydroheliotridine to DNA and the effect of it and other compounds on repair synthesis in main and satellite band DNA. This study was aimed at elucidating the mechanisms of the preferential depression of satellite DNA synthesis by dehydroheliotridine (DHH). DHH was found to induce repair synthesis to the same extent in both main and satellite band DNA in cultured sheep lymphocytes. This was also the case with acridine orange, nitrogen mustard (HN2) and ethyl methane-sulphonate (EMS). Using analytical equilibrium ultracentrifugation no difference was found between the extents of in vitro binding of DHH by main and satellite band DNA. From these results it was concluded that the depression of the synthesis of satellite DNA could not be explained by either its preferential binding of DHH or by less effective repair mechanisms. Radiolabelled DHH when added to synchronized cultures of ovine kidney cells was found to be preferentially bound to the satellite DNA (one DHH molecule to 6000 nucleotides) compared with the main band DNA (one to 10 000). When 5-bromodeoxyuridine (BUdR) was added to the cultures no DHH label was found in the heavy, semiconservatively replicated DNA band. From these findings it is suggested that attack may occur during mitosis where all of the satellite DNA may be undergoing synthesis at the same time, thus explaining the increased amount of DHH bound to the satellite."} {"id": "PMID:1269046", "title": "Some studies of the effects of aflatoxin B1 in vivo and in vitro on nucleic acid synthesis in rat and mouse.", "content": "The mouse compared with the rat, is more resistent to the acute toxic action of aflatoxin B1 and is refractory to its hepatocarcinogenic properties. Aflatoxin B1 inhibits DNA synthesis more strongly than RNA synthesis in the rat, and both nucleic acid syntheses more strongly in rat than in the mouse. Mouse hepatic microsomes, like those of the rat, are capable of metabolizing aflatoxin B1 in vitro in the presence of NADPH, to an active form which binds to DNA both in solution and in intact nuclei and also inhibits nuclear RNA synthesis. Non NADPH-dependent binding of aflatoxin B1 to nuclei is not effective in inhibiting RNA polymerase and is largely removed by washing with lipid solvents. Mouse nuclear RNA polymerases particularly Mn 2+ (NH4)2SO4 primed acitivity are more resistant to inhibition in vitro by activated aflatoxin B1 than are the corresponding enzyme activities in rat liver nuclei. This would appear to be due to the bound aflatoxin B1 being less efficient in the case of the mouse nucleus, in inhibiting RNA synthesis. Mouse liver slices exhibit a much lesser degree of inhibition of RNA synthesis by aflatoxin B1 than do rat liver slices. Accompanying this is a lower level of binding of aflatoxin B1 to subcellular particulate fractions in the mouse liver slice compared to the rat, this disparity being most marked in the case of the nuclear fraction. The suggestion is made that the resistance of RNA synthesis in the mouse liver, to aflatoxin B1, and perhaps also resistance to its toxicity, is dependent, not on a lower capacity to activate the toxin, but (a) on a less efficient inhibition of RNA synthesis by nuclear bound toxin, and (b) a detoxifying mechanism at least partially situated in the cytosol fraction.", "contents": "Some studies of the effects of aflatoxin B1 in vivo and in vitro on nucleic acid synthesis in rat and mouse. The mouse compared with the rat, is more resistent to the acute toxic action of aflatoxin B1 and is refractory to its hepatocarcinogenic properties. Aflatoxin B1 inhibits DNA synthesis more strongly than RNA synthesis in the rat, and both nucleic acid syntheses more strongly in rat than in the mouse. Mouse hepatic microsomes, like those of the rat, are capable of metabolizing aflatoxin B1 in vitro in the presence of NADPH, to an active form which binds to DNA both in solution and in intact nuclei and also inhibits nuclear RNA synthesis. Non NADPH-dependent binding of aflatoxin B1 to nuclei is not effective in inhibiting RNA polymerase and is largely removed by washing with lipid solvents. Mouse nuclear RNA polymerases particularly Mn 2+ (NH4)2SO4 primed acitivity are more resistant to inhibition in vitro by activated aflatoxin B1 than are the corresponding enzyme activities in rat liver nuclei. This would appear to be due to the bound aflatoxin B1 being less efficient in the case of the mouse nucleus, in inhibiting RNA synthesis. Mouse liver slices exhibit a much lesser degree of inhibition of RNA synthesis by aflatoxin B1 than do rat liver slices. Accompanying this is a lower level of binding of aflatoxin B1 to subcellular particulate fractions in the mouse liver slice compared to the rat, this disparity being most marked in the case of the nuclear fraction. The suggestion is made that the resistance of RNA synthesis in the mouse liver, to aflatoxin B1, and perhaps also resistance to its toxicity, is dependent, not on a lower capacity to activate the toxin, but (a) on a less efficient inhibition of RNA synthesis by nuclear bound toxin, and (b) a detoxifying mechanism at least partially situated in the cytosol fraction."} {"id": "PMID:1269047", "title": "DNA repair synthesis in guinea pig pancreatic slices following in vitro exposure to N-nitrosomethylurethane.", "content": "The incorporation of thymidine into DNA in the presence of hydroxyurea (HU) by guinea pig pancreatic slices following exposure to N-nitrosomethylurethane (NMUT) was used to follow DNA repair synthesis. HU was used to suppress normal replicative DNA synthesis. Slices from the duodenal segment of the pancreas were exposed for periods of 15 to 90 min to NMUT at concentrations of 2 to 20 mM, then incubated in tritiated thymidine ([H3]-TdR) free of carcinogen, and radioactivity in DNA was determined. NMUT induced a a dose- and time-dependent increase in HU-insensitive thymidine incorporation. This stimulated incorporation, which could be attributed to repair synthesis, occurred immediately following the treatment and was largely complete within 3 h.", "contents": "DNA repair synthesis in guinea pig pancreatic slices following in vitro exposure to N-nitrosomethylurethane. The incorporation of thymidine into DNA in the presence of hydroxyurea (HU) by guinea pig pancreatic slices following exposure to N-nitrosomethylurethane (NMUT) was used to follow DNA repair synthesis. HU was used to suppress normal replicative DNA synthesis. Slices from the duodenal segment of the pancreas were exposed for periods of 15 to 90 min to NMUT at concentrations of 2 to 20 mM, then incubated in tritiated thymidine ([H3]-TdR) free of carcinogen, and radioactivity in DNA was determined. NMUT induced a a dose- and time-dependent increase in HU-insensitive thymidine incorporation. This stimulated incorporation, which could be attributed to repair synthesis, occurred immediately following the treatment and was largely complete within 3 h."} {"id": "PMID:1269048", "title": "Studies on pulmonary aryl hydrocarbon hydroxylase activity in inbred strains of mice.", "content": "Pulmonary and hepatic levels of aryl hydrocarbon hydroxylase (AHH) were studied in inbred strains of mice following intratracheal (i.t.) instillation of 3-methylcholanthrene (MCA). I.t. instillation of 188 mug MCA in sterile 0.2% gelatin in saline resulted in preferential induction of pulmonary AHH. After treatment with this dose of MCA, the pulmonary AHH levels of strains C57BL/6Cum, C57BL/6J, BALB/cMai, C3H/fMai, and C57L/J were observed to be induced within 24 h after treatment. Strains DBA/2Cum, AKR/J, SJL/J, DBA/2J and RF/J expressed no such increase. At a dose of 500 mug MCA, the pulmonary tissue of DBA/2 mice did express a 4-fold increase. This increase in AHH was determined to be quite different from the increase observed in C57BL/6 mice by: (1) specific activity of the enzymes, (2) genetic regulation, (3) susceptibility to inhibition by 7,8-benzoflavone, and (4) spectral properties of the associated cytochromes. It was of major importance that induction of pulmonary AHH was observed to be regulated by a single dominant gene in crosses involving the C57BL/6Cum and DBA/2Cum strains of mice. Results were discussed with the view in mind that these genetically regulated levels of AHH may play a role in susceptibility to cancers induced by polycyclic aromatic hydrocarbon carcinogens.", "contents": "Studies on pulmonary aryl hydrocarbon hydroxylase activity in inbred strains of mice. Pulmonary and hepatic levels of aryl hydrocarbon hydroxylase (AHH) were studied in inbred strains of mice following intratracheal (i.t.) instillation of 3-methylcholanthrene (MCA). I.t. instillation of 188 mug MCA in sterile 0.2% gelatin in saline resulted in preferential induction of pulmonary AHH. After treatment with this dose of MCA, the pulmonary AHH levels of strains C57BL/6Cum, C57BL/6J, BALB/cMai, C3H/fMai, and C57L/J were observed to be induced within 24 h after treatment. Strains DBA/2Cum, AKR/J, SJL/J, DBA/2J and RF/J expressed no such increase. At a dose of 500 mug MCA, the pulmonary tissue of DBA/2 mice did express a 4-fold increase. This increase in AHH was determined to be quite different from the increase observed in C57BL/6 mice by: (1) specific activity of the enzymes, (2) genetic regulation, (3) susceptibility to inhibition by 7,8-benzoflavone, and (4) spectral properties of the associated cytochromes. It was of major importance that induction of pulmonary AHH was observed to be regulated by a single dominant gene in crosses involving the C57BL/6Cum and DBA/2Cum strains of mice. Results were discussed with the view in mind that these genetically regulated levels of AHH may play a role in susceptibility to cancers induced by polycyclic aromatic hydrocarbon carcinogens."} {"id": "PMID:1269049", "title": "The role of liver glutathione in the acute toxicity of retrorsine to rats.", "content": "(1) Two procedures have been used to change the glutathione concentration in the livers of male rats. The glutathione level is increased to about double that of the controls, 0.5 h after the administration of cysteine (200 mg/kg, i.p.) and to about 25% that of controls, 1 h after the administration of 2-chloroethanol (30 mg/kg, i.p.). (2) The acute LD50 of retrorsine to rats (42 mg/kg) is increased by pretreatment with cysteine to 83 mg/kg and decreased by pre-treatment with chloroethanol to 23 mg/kg. In all three groups, deaths are accompanied by haemorrhagic centrilobular necrosis of the liver. (3) 2 h after the administration of retrorsine to rats (60 mg/kg), the levels of pyrrolic metabolites in the livers of animals pre-dosed with cysteine or chloroethanol are respectively about 60% and 200% those of rats given no pre-treatment. (4) Neither in the normal nor in the pre-treated rats dose retrorsine (60 mg/kg) cause a detectable fall in liver glutathione concentration 0.5-4 h after dosing. By 24 h, the glutathione concentration in the livers of the retrorsine-dosed rats is higher than those of the corresponding controls. There was no significant change in the liver weights of the treated rats relative to the controls. (5) Treatment of rats with retrorsine (60 mg/kg) causes a fall in the liver concentrations of cytochrome P-450, 24 h after dosing. This loss of cytochrome P-450 is increased in rats pre-treated with chloroethanol. The concentrations of cytochrome b5 in the same animals are not significantly reduced.", "contents": "The role of liver glutathione in the acute toxicity of retrorsine to rats. (1) Two procedures have been used to change the glutathione concentration in the livers of male rats. The glutathione level is increased to about double that of the controls, 0.5 h after the administration of cysteine (200 mg/kg, i.p.) and to about 25% that of controls, 1 h after the administration of 2-chloroethanol (30 mg/kg, i.p.). (2) The acute LD50 of retrorsine to rats (42 mg/kg) is increased by pretreatment with cysteine to 83 mg/kg and decreased by pre-treatment with chloroethanol to 23 mg/kg. In all three groups, deaths are accompanied by haemorrhagic centrilobular necrosis of the liver. (3) 2 h after the administration of retrorsine to rats (60 mg/kg), the levels of pyrrolic metabolites in the livers of animals pre-dosed with cysteine or chloroethanol are respectively about 60% and 200% those of rats given no pre-treatment. (4) Neither in the normal nor in the pre-treated rats dose retrorsine (60 mg/kg) cause a detectable fall in liver glutathione concentration 0.5-4 h after dosing. By 24 h, the glutathione concentration in the livers of the retrorsine-dosed rats is higher than those of the corresponding controls. There was no significant change in the liver weights of the treated rats relative to the controls. (5) Treatment of rats with retrorsine (60 mg/kg) causes a fall in the liver concentrations of cytochrome P-450, 24 h after dosing. This loss of cytochrome P-450 is increased in rats pre-treated with chloroethanol. The concentrations of cytochrome b5 in the same animals are not significantly reduced."} {"id": "PMID:1269065", "title": "The synthesis of chiral glycerides starting from D- and L-serine.", "content": "A method for synthesizing chiral glycerides starting from L- or D-serine is described. Optically-active serine (both enantiomers are commerically available) was transformed into glyceric acid by stereospecific diazotization. The configuration at carbon atom 2 was maintained during the reaction. The glyceric acid was then converted into optically pure isopropylideneglycerol - which is an important intermediate in the synthesis of mono-, di- and triglyderides - by esterification followed by acetalization with acetone and reduction with lithium aluminium hydride. Reaction of this intermediate with triphenylphosphine in tetrachloromethane followed by acid-catalysed hydrolysis and dehydrohalogenation provided optically-active glycidol (2,3-epoxy-1-propanol). The epoxy ring of an ester of glycidol and a fatty acid was then opened stereospecifically with retention of configuration by heating the glycidol ester in the presence of a second fatty acid and a catalyst. This yielded a chiral 1,3-diglyceride which could be converted into a chiral triglyceride.", "contents": "The synthesis of chiral glycerides starting from D- and L-serine. A method for synthesizing chiral glycerides starting from L- or D-serine is described. Optically-active serine (both enantiomers are commerically available) was transformed into glyceric acid by stereospecific diazotization. The configuration at carbon atom 2 was maintained during the reaction. The glyceric acid was then converted into optically pure isopropylideneglycerol - which is an important intermediate in the synthesis of mono-, di- and triglyderides - by esterification followed by acetalization with acetone and reduction with lithium aluminium hydride. Reaction of this intermediate with triphenylphosphine in tetrachloromethane followed by acid-catalysed hydrolysis and dehydrohalogenation provided optically-active glycidol (2,3-epoxy-1-propanol). The epoxy ring of an ester of glycidol and a fatty acid was then opened stereospecifically with retention of configuration by heating the glycidol ester in the presence of a second fatty acid and a catalyst. This yielded a chiral 1,3-diglyceride which could be converted into a chiral triglyceride."} {"id": "PMID:1269067", "title": "Gas chromatographic analysis of synthetic glycidol esters, mono-, di- and triglycerides.", "content": "The gas chromatographic analysis of glycidol esters and mono-, di-,and triglycerides of palmitic-, stearic-, and oleic acid mixtures is described. The composition of the products was determined by gas chromatography on OV-17 after trimethylsilylation. Base-line separations between 1- and 2-monoglycerides and between 1,2- and 1,3-diglycerides were obtained. Isomerisation of the trimethylsilyl ethers of monoglycerides was not observed, contrary to published work.", "contents": "Gas chromatographic analysis of synthetic glycidol esters, mono-, di- and triglycerides. The gas chromatographic analysis of glycidol esters and mono-, di-,and triglycerides of palmitic-, stearic-, and oleic acid mixtures is described. The composition of the products was determined by gas chromatography on OV-17 after trimethylsilylation. Base-line separations between 1- and 2-monoglycerides and between 1,2- and 1,3-diglycerides were obtained. Isomerisation of the trimethylsilyl ethers of monoglycerides was not observed, contrary to published work."} {"id": "PMID:1269068", "title": "Preparation and properties of vesicles enclosed by fatty acid membranes.", "content": "Stable preparations of microscopic particles were obtained from long-chain fatty acids by mechanical agitation of evaporated films in presence of buffer solutions. Oleic and linoleic acids were used. Studies of osmotic swelling and shrinking of the particles indicated that they are enclosed by semipermeable membranes. The particles, which were named ufasomes, are also capable of entrapping glucose in spaces inaccessible to enzymes. It was concluded that the ufasomes closely resemble phospholipid liposomes in their structure and properties.", "contents": "Preparation and properties of vesicles enclosed by fatty acid membranes. Stable preparations of microscopic particles were obtained from long-chain fatty acids by mechanical agitation of evaporated films in presence of buffer solutions. Oleic and linoleic acids were used. Studies of osmotic swelling and shrinking of the particles indicated that they are enclosed by semipermeable membranes. The particles, which were named ufasomes, are also capable of entrapping glucose in spaces inaccessible to enzymes. It was concluded that the ufasomes closely resemble phospholipid liposomes in their structure and properties."} {"id": "PMID:1269071", "title": "Vascular capacitance and fluid shifts in dogs during prolonged hemorrhagic hypotension.", "content": "The mean circulatory pressure (Pmc) in dogs anesthetized with chloralose-urethane was estimated from 0.5 to 150 minutes after hemorrhages of 0, 17, or 34 ml/kg, or that volume giving an arterial pressure (Pa) of 40 mm Hg. The Pmc was determined by fibrillating the heart and then rapidly pumping blood from aorta to vena cava until Pa=venous pressure (Pv)=Pmc. Within about 10 seconds, the heart was defibrillated. Vascular compliance was estimated as the ratio of a test blood volume change (0, +/- 8.5, or 17 ml/kg) to the change in Pmc, determined 0.5 minute after the start of the test volume change. Erythrocyte and plasma volumes were measured by 51Cr-erythrocyte and 125I-albumin dilution. In response to prolonged hemorrhage: (1) the total vascular compliance apparently decreased; (2) most of the changes in capacity vessels occurred within 5 minutes, and indeed a large part of the response probably had occurred by the time of the first measurement at 30 seconds; (3) the progressive recovery in Pmc after 5 minutes was primarily from fluid shifting into the vasculature; (4) even after 2 hours of severe hemorrhagic hypotension, the venoconstriction was not lost; but (5) after an hour of severe hemorrhagic hypotension (arterial pressure of 40 mm Hg) there was water loss from the vasculature, because plasma protein and erythrocyte concentrations and plasma oncotic pressure increased.", "contents": "Vascular capacitance and fluid shifts in dogs during prolonged hemorrhagic hypotension. The mean circulatory pressure (Pmc) in dogs anesthetized with chloralose-urethane was estimated from 0.5 to 150 minutes after hemorrhages of 0, 17, or 34 ml/kg, or that volume giving an arterial pressure (Pa) of 40 mm Hg. The Pmc was determined by fibrillating the heart and then rapidly pumping blood from aorta to vena cava until Pa=venous pressure (Pv)=Pmc. Within about 10 seconds, the heart was defibrillated. Vascular compliance was estimated as the ratio of a test blood volume change (0, +/- 8.5, or 17 ml/kg) to the change in Pmc, determined 0.5 minute after the start of the test volume change. Erythrocyte and plasma volumes were measured by 51Cr-erythrocyte and 125I-albumin dilution. In response to prolonged hemorrhage: (1) the total vascular compliance apparently decreased; (2) most of the changes in capacity vessels occurred within 5 minutes, and indeed a large part of the response probably had occurred by the time of the first measurement at 30 seconds; (3) the progressive recovery in Pmc after 5 minutes was primarily from fluid shifting into the vasculature; (4) even after 2 hours of severe hemorrhagic hypotension, the venoconstriction was not lost; but (5) after an hour of severe hemorrhagic hypotension (arterial pressure of 40 mm Hg) there was water loss from the vasculature, because plasma protein and erythrocyte concentrations and plasma oncotic pressure increased."} {"id": "PMID:1269072", "title": "Atrial receptors with nonmedullated vagal afferents in the cat. Discharge frequency and pattern in relation to atrial pressure.", "content": "The response of 14 atrial receptors with nonmedullated vagal afferents to changes in atrial pressure was determined in anesthetized thoracotomized cats. Recordings were made from 11 single fibers and three two-fiber filaments. Mean conduction velocity was 0.9 m/sec (range, 0.35 to 2.2 m/sec). During the control period, either no activity was detected or there was a sparse discharge (mean, 1.4 impulses/sec), which occasionally was related to the a or v waves. As atrial pressure was increased by transfusion or by occlusion of the aortic, pulmonary arterial, mitral, and tricuspid orifices, an increased rate of firing occurred, often related to the atrial v wave. The threshold for individual receptors was between 2 and 3 mm Hg (mean pressure) in the right atrium, and 5 and 12 mm Hg in the left atrium. The maximal firing rate was 5-11 impulses/sec for right atrial and 10-20 impulses/sec for left atrial receptors. The receptors were localized by probing the opened heart, and were identified in both atria, in the interatrial septum, and in the atrial-venous junctions. Thus receptors connected to vagal C fibers are present throughout both atria and are activated by moderate changes in pressure.", "contents": "Atrial receptors with nonmedullated vagal afferents in the cat. Discharge frequency and pattern in relation to atrial pressure. The response of 14 atrial receptors with nonmedullated vagal afferents to changes in atrial pressure was determined in anesthetized thoracotomized cats. Recordings were made from 11 single fibers and three two-fiber filaments. Mean conduction velocity was 0.9 m/sec (range, 0.35 to 2.2 m/sec). During the control period, either no activity was detected or there was a sparse discharge (mean, 1.4 impulses/sec), which occasionally was related to the a or v waves. As atrial pressure was increased by transfusion or by occlusion of the aortic, pulmonary arterial, mitral, and tricuspid orifices, an increased rate of firing occurred, often related to the atrial v wave. The threshold for individual receptors was between 2 and 3 mm Hg (mean pressure) in the right atrium, and 5 and 12 mm Hg in the left atrium. The maximal firing rate was 5-11 impulses/sec for right atrial and 10-20 impulses/sec for left atrial receptors. The receptors were localized by probing the opened heart, and were identified in both atria, in the interatrial septum, and in the atrial-venous junctions. Thus receptors connected to vagal C fibers are present throughout both atria and are activated by moderate changes in pressure."} {"id": "PMID:1269073", "title": "Electrogenesis of increased norepinephrine sensitivity of arterial vascular muscle in hypertension.", "content": "The possibility that the vascular muscle cell might contribute to the development of essential hypertension by being more responsive to norepinephrine because of an inherently lower membrane potential (Em) was investigated. Experiments were designed to test the hypothesis that Em of arterial vascular muscle cells from spontaneously hypertensive rats (SHR) are less negative than those from matched Kyoto normotensive rats (KNR). The caudal artery, a muscular, densely innervated regulating artery 300-400 mum in outside diameter, which is activated by graded (nonspiking) depolarization to produce a maintained contraction, was studied. Vascular muscle cells from SHR always had less negative Em than those from KNR at 16 degrees C, but not at 36 degrees C, over a range of K+ concentrations from 2.7 mM to 150 mM. From the relationship between Em and K+ concentration, intracellular K+ concentration ([K+]i) was estimated to be 150 mM for SHR and 170 mM for KNR. The caudal artery undergoes a large depolarization when K+ is removed from the superfusing solution and a transient hyperpolarization that exceeds the calculated EK (potassium equilibrium potential) when K+ is replaced. The magnitude of the hyper-polarization on returning to 30 mM or 50 mM K+ always was greater for vascular muscle of SHR than KNR. The apparently lower [K+]i and more active (compensating) electrogenic ion transport in the SHR vascular muscle cells thus result in an unaltered Em at body temperature in the physiological range of K+ concentrations. However, depolarization by norepinephrine was greater over the middle of the dose-response curve, and this greater depolarization caused the contractions of SHR arteries to be greater. The altered electrogenesis of the SHR vascular muscle cells is postulated to provide a mechanism for the increased reactivity of arteries to norepinephrein in hypertension.", "contents": "Electrogenesis of increased norepinephrine sensitivity of arterial vascular muscle in hypertension. The possibility that the vascular muscle cell might contribute to the development of essential hypertension by being more responsive to norepinephrine because of an inherently lower membrane potential (Em) was investigated. Experiments were designed to test the hypothesis that Em of arterial vascular muscle cells from spontaneously hypertensive rats (SHR) are less negative than those from matched Kyoto normotensive rats (KNR). The caudal artery, a muscular, densely innervated regulating artery 300-400 mum in outside diameter, which is activated by graded (nonspiking) depolarization to produce a maintained contraction, was studied. Vascular muscle cells from SHR always had less negative Em than those from KNR at 16 degrees C, but not at 36 degrees C, over a range of K+ concentrations from 2.7 mM to 150 mM. From the relationship between Em and K+ concentration, intracellular K+ concentration ([K+]i) was estimated to be 150 mM for SHR and 170 mM for KNR. The caudal artery undergoes a large depolarization when K+ is removed from the superfusing solution and a transient hyperpolarization that exceeds the calculated EK (potassium equilibrium potential) when K+ is replaced. The magnitude of the hyper-polarization on returning to 30 mM or 50 mM K+ always was greater for vascular muscle of SHR than KNR. The apparently lower [K+]i and more active (compensating) electrogenic ion transport in the SHR vascular muscle cells thus result in an unaltered Em at body temperature in the physiological range of K+ concentrations. However, depolarization by norepinephrine was greater over the middle of the dose-response curve, and this greater depolarization caused the contractions of SHR arteries to be greater. The altered electrogenesis of the SHR vascular muscle cells is postulated to provide a mechanism for the increased reactivity of arteries to norepinephrein in hypertension."} {"id": "PMID:1269074", "title": "The relationship between overdrive suppression and overdrive excitation in ventricular pacemakers in dogs.", "content": "We studied the excitatory and inhibitory effects of overdrive on idioventricular pacemakers in anesthetized dogs with recently induced complete atrioventricular block. The following results were obtained: (1) a slow driving rate may induce a temporary rhythm which may be reinstituted with additional stimuli; (2) the induced rhythm may appear as coupled extrasystoles which, on interruption of the drive, are found to be self-sustaining; (3) during continued slow driving, extrasystoles may appear and disappear in a cyclical manner; (4) a short period of fast driving may be followed by a fast new rhythm, the rate and duration of which are a function of the rate and duration of drive; (5) fast driving may induce a new rhythm at a rate below predrive control; (6) after a long period fast driving, only suppression follows; and (7) intermittent periods of fast driving lead to a summation of inhibition with each successive period. These results suggest the following conclusions: (1) under certain conditions, electrical driving instead of inducing suppression may induce a rhythm (\"overdrive excitation\") at a rate similar to, faster then, or slower (\"inhibited excitation\") than control; (2) the duration of diastole and the number of driven beats are major factors in the induction of new rhythms; and (3) overdrive excitation is counteracted by overdrive inhibition, with development of the former requiring fewer beats than the latter.", "contents": "The relationship between overdrive suppression and overdrive excitation in ventricular pacemakers in dogs. We studied the excitatory and inhibitory effects of overdrive on idioventricular pacemakers in anesthetized dogs with recently induced complete atrioventricular block. The following results were obtained: (1) a slow driving rate may induce a temporary rhythm which may be reinstituted with additional stimuli; (2) the induced rhythm may appear as coupled extrasystoles which, on interruption of the drive, are found to be self-sustaining; (3) during continued slow driving, extrasystoles may appear and disappear in a cyclical manner; (4) a short period of fast driving may be followed by a fast new rhythm, the rate and duration of which are a function of the rate and duration of drive; (5) fast driving may induce a new rhythm at a rate below predrive control; (6) after a long period fast driving, only suppression follows; and (7) intermittent periods of fast driving lead to a summation of inhibition with each successive period. These results suggest the following conclusions: (1) under certain conditions, electrical driving instead of inducing suppression may induce a rhythm (\"overdrive excitation\") at a rate similar to, faster then, or slower (\"inhibited excitation\") than control; (2) the duration of diastole and the number of driven beats are major factors in the induction of new rhythms; and (3) overdrive excitation is counteracted by overdrive inhibition, with development of the former requiring fewer beats than the latter."} {"id": "PMID:1269075", "title": "Abnormal ion and water composition of veins and normotensive arteries in coarctation hypertension in rats.", "content": "We examined the water, sodium, and potassium composition of the thoracic aorta, abdominal aorta (plus iliac arteries), and veins (vena cava and portal vein) from rats with aortic coarctation. The aortas of 10 rats (group A) were coarcted above the renal arteries to produce hypertension. Control groups consisted of 10 rats sham-coarcted above and 10 rats coarcted below the renal arteries. In group A rats heart weights and carotid artery pressures were elevated over controls (P less than 0.01), whereas there were no significant differences in femoral arterial pressures. In group A rats both the hypertensive thoracic aorta and the normotensive abdominal aorta contained about 20% more water per unit of wet weight, and about 35% and 60% more sodium and potassium, respectively, per unit of dry weight than did the corresponding portions of aorta from control rats (P less than 0.01). In group A rats water (P less than 0.01), sodium (P less than 0.02), and potassium (P less than 0.05) contents of veins also were increased. There were no significant correlations between level of carotid arterial pressure and magnitude of changes in arterial and venous composition, nor were there significant differences between the magnitude of changes in the normotensive and hypertensive portions of the aorta. These results indicate that in rats abnormalities in vascular wall salt and water content are not necessarily a direct effect of the elevated pressure in hypertension.", "contents": "Abnormal ion and water composition of veins and normotensive arteries in coarctation hypertension in rats. We examined the water, sodium, and potassium composition of the thoracic aorta, abdominal aorta (plus iliac arteries), and veins (vena cava and portal vein) from rats with aortic coarctation. The aortas of 10 rats (group A) were coarcted above the renal arteries to produce hypertension. Control groups consisted of 10 rats sham-coarcted above and 10 rats coarcted below the renal arteries. In group A rats heart weights and carotid artery pressures were elevated over controls (P less than 0.01), whereas there were no significant differences in femoral arterial pressures. In group A rats both the hypertensive thoracic aorta and the normotensive abdominal aorta contained about 20% more water per unit of wet weight, and about 35% and 60% more sodium and potassium, respectively, per unit of dry weight than did the corresponding portions of aorta from control rats (P less than 0.01). In group A rats water (P less than 0.01), sodium (P less than 0.02), and potassium (P less than 0.05) contents of veins also were increased. There were no significant correlations between level of carotid arterial pressure and magnitude of changes in arterial and venous composition, nor were there significant differences between the magnitude of changes in the normotensive and hypertensive portions of the aorta. These results indicate that in rats abnormalities in vascular wall salt and water content are not necessarily a direct effect of the elevated pressure in hypertension."} {"id": "PMID:1269076", "title": "Role of resistance and exchange vessels in local microvascular control of skeletal muscle oxygenation in the dog.", "content": "The effects of reduction in perfusion pressure, arterial hypoxia, muscle contraction, and adrenergic stimulation on the hindlimb muscle circulation were studied. Under normal conditions (venous PO2 greater than or equal to 40 mm Hg), oxygen delivery to the muscle was maintained mainly by large increases in the capillary exchange capacity and the oxygen extraction ratio in accord with tissue demand following the application of the above stresses. The participation of the resistance vessels under these conditions was minimal. The prevailing venous oxygen tension then was reduced by several means and the response of vascular resistance and capillary exchange capacity to the same stresses was reexamined. At the lower prevailing venous PO2, the sensitivity of the resistance vessels to metabolic and hemodynamic disturbances was greatly increased. Consequently, blood flow autoregulation, functional hyperemia, and hypoxic hyperemia were more intense when venous oxygen tension was low. In contrast, the contribution of exchange capacity was diminished, probably owing to the fact that most of the capillaries already are open at low venous PO2. These data suggest that the locus of local microvascular control of muscle oxygenation shifts from the normally more sensitive precapillary sphincters to the proximal flow-controlling arterioles as the prevailing venous oxygen tension falls. Yet, although the relative contribution of the resistance and exchange vessels to intrinsic regulation of tissue oxygenation is related to the prevailing venous oxygen tension, the two compensatory mechanisms operating in concert maintain tissue PO2 above the critical level over a wide range of stresses.", "contents": "Role of resistance and exchange vessels in local microvascular control of skeletal muscle oxygenation in the dog. The effects of reduction in perfusion pressure, arterial hypoxia, muscle contraction, and adrenergic stimulation on the hindlimb muscle circulation were studied. Under normal conditions (venous PO2 greater than or equal to 40 mm Hg), oxygen delivery to the muscle was maintained mainly by large increases in the capillary exchange capacity and the oxygen extraction ratio in accord with tissue demand following the application of the above stresses. The participation of the resistance vessels under these conditions was minimal. The prevailing venous oxygen tension then was reduced by several means and the response of vascular resistance and capillary exchange capacity to the same stresses was reexamined. At the lower prevailing venous PO2, the sensitivity of the resistance vessels to metabolic and hemodynamic disturbances was greatly increased. Consequently, blood flow autoregulation, functional hyperemia, and hypoxic hyperemia were more intense when venous oxygen tension was low. In contrast, the contribution of exchange capacity was diminished, probably owing to the fact that most of the capillaries already are open at low venous PO2. These data suggest that the locus of local microvascular control of muscle oxygenation shifts from the normally more sensitive precapillary sphincters to the proximal flow-controlling arterioles as the prevailing venous oxygen tension falls. Yet, although the relative contribution of the resistance and exchange vessels to intrinsic regulation of tissue oxygenation is related to the prevailing venous oxygen tension, the two compensatory mechanisms operating in concert maintain tissue PO2 above the critical level over a wide range of stresses."} {"id": "PMID:1269077", "title": "Experimental evidence for regional cardiac influence in body surface isopotential maps of dogs.", "content": "Isopotential mpas based on 192-200 body surface electrocardiograms were obtained for 20 dogs during multiple patterns of ventricular activation. The purposes of the study were to determine whether the cardiac location of events responsible for surface potentials had a recognizable influence on surface potential patterns and to examine the influence of electrical events occurring simultaneously in multiple cardiac regions. Substantially different effects of electrical activity in various cardiac regions on body surface potentials were evidenced by the body surface location of potential maxima and minima and by patterns of isopotential lines during early portions of ventricular excitation initiated at different ventricular sites. Simultaneous stimulation at some sites gave surface potential distributions with multiple extrema. These were demonstrated to be due to effects of the different cardiac regions, because addition of potentials due to stimulation of the individual sites duplicated those associated with simultaneous stimulation of the same sites. It was also shown that body surface locations of maxima and minima are not related in the same manner to the cardiac location of the responsible events when these events are present in single and multiple regions. Slopes of potentials due to events in single cardiac regions were shown to combine with slopes produced by events in other regions to yield maxima or minima at new body surface locations. Results of the study support the possibility of regional cardiac examination by electrocardiography but suggest that this will require quantitative descriptions of the details of potential patterns in addition to the location of potential peaks.", "contents": "Experimental evidence for regional cardiac influence in body surface isopotential maps of dogs. Isopotential mpas based on 192-200 body surface electrocardiograms were obtained for 20 dogs during multiple patterns of ventricular activation. The purposes of the study were to determine whether the cardiac location of events responsible for surface potentials had a recognizable influence on surface potential patterns and to examine the influence of electrical events occurring simultaneously in multiple cardiac regions. Substantially different effects of electrical activity in various cardiac regions on body surface potentials were evidenced by the body surface location of potential maxima and minima and by patterns of isopotential lines during early portions of ventricular excitation initiated at different ventricular sites. Simultaneous stimulation at some sites gave surface potential distributions with multiple extrema. These were demonstrated to be due to effects of the different cardiac regions, because addition of potentials due to stimulation of the individual sites duplicated those associated with simultaneous stimulation of the same sites. It was also shown that body surface locations of maxima and minima are not related in the same manner to the cardiac location of the responsible events when these events are present in single and multiple regions. Slopes of potentials due to events in single cardiac regions were shown to combine with slopes produced by events in other regions to yield maxima or minima at new body surface locations. Results of the study support the possibility of regional cardiac examination by electrocardiography but suggest that this will require quantitative descriptions of the details of potential patterns in addition to the location of potential peaks."} {"id": "PMID:1269078", "title": "Maintained stroke volume but impaired arterial oxygenation in man at high altitude with supplemental CO2.", "content": "Hypobaric hypoxia causes hypocapina and alkalosis, hemoconcentration and increased hematocrit, and a decreased cardiac stroke volume. To assess the role of the hypocapnic alkalosis in causing these other changes, five men were exposed to hypobaric hypoxia at a barometric pressure (PB) of 440 torr with an alveolar O2 tension of 55 torr for 5 days with 3.77% CO2 added to the atmosphere to prevent alkalosis. They did not lose weight, and arterial CO2 tension, pH, and cardiac stroke volume were unchanged. An unchanged hematocrit implied an unchanged plasma volume. During exercise to maximum, stroke volumes equaled sea level values but arterial hypoxemia was profound, the arterial O2 tension being 39 torr. By contrast, three men at high altitude without CO2 supplementation (PB=455 torr; alveolar PO2=56 torr) had weight loss, hypocapnia, alkalosis, and decreased stroke volume. Increased hematocrits suggested decreased plasma volumes. During exercise, arterial PO2 (48 torr) was higher than in the group receiving CO2. Maximum oxygen uptakes were decreased to a similar degree in the two groups. Catecholamine excretion doubled in the group with CO2 but in the group without CO2 catechoamine excretion was unchanged. A normal pH at high altitude apparently maintained plasma volume, which, with the increased catecholamine excretion, may have prevented a decrease in stroke volume. However, the subjects with CO2 added did not have enhanced oxygen transport, because their arterial oxygenation was impaired.", "contents": "Maintained stroke volume but impaired arterial oxygenation in man at high altitude with supplemental CO2. Hypobaric hypoxia causes hypocapina and alkalosis, hemoconcentration and increased hematocrit, and a decreased cardiac stroke volume. To assess the role of the hypocapnic alkalosis in causing these other changes, five men were exposed to hypobaric hypoxia at a barometric pressure (PB) of 440 torr with an alveolar O2 tension of 55 torr for 5 days with 3.77% CO2 added to the atmosphere to prevent alkalosis. They did not lose weight, and arterial CO2 tension, pH, and cardiac stroke volume were unchanged. An unchanged hematocrit implied an unchanged plasma volume. During exercise to maximum, stroke volumes equaled sea level values but arterial hypoxemia was profound, the arterial O2 tension being 39 torr. By contrast, three men at high altitude without CO2 supplementation (PB=455 torr; alveolar PO2=56 torr) had weight loss, hypocapnia, alkalosis, and decreased stroke volume. Increased hematocrits suggested decreased plasma volumes. During exercise, arterial PO2 (48 torr) was higher than in the group receiving CO2. Maximum oxygen uptakes were decreased to a similar degree in the two groups. Catecholamine excretion doubled in the group with CO2 but in the group without CO2 catechoamine excretion was unchanged. A normal pH at high altitude apparently maintained plasma volume, which, with the increased catecholamine excretion, may have prevented a decrease in stroke volume. However, the subjects with CO2 added did not have enhanced oxygen transport, because their arterial oxygenation was impaired."} {"id": "PMID:1269079", "title": "Mechanical stimuli exciting type A atrial vagal receptors in the cat.", "content": "The activity of type A right atrial vagal receptors was recorded from the right cervical vagus in cats anesthetized with sodium pentobarbital, immobilized with gallamine, and with their chests open. Nerve impulses initiated by receptor activation were recorded simultaneously with instantaneous right atrial pressure and dimensional changes under various hemodynamic conditions. Atrial volume changes induced by infusion of saline, bleeding, and occlusion of the inferior vena cava did not alter consistently the systolic activity of the receptors. Electrical stimulation of the right stellate ganglion significantly increased the frequency of discharge during systole, whereas electrical stimulation of the left thoracic vagus significantly reduced the frequency of discharge. These inotropic interventions produced similar effects when the heart was paced at a fixed rate. Pacing the right atrial appendage increased the systolic discharge of the receptors only when at high rates the atrium contracted against closed atrioventricular valves. To investigate the influence of tonic efferent sympathetic activity on spontaneous receptor discharge, three receptors were studied before and after bilateral surgical stellectomy, and in cats with their chest closed three receptors were studied before and after infusion of propranolol. Both of these interventions markedly reduced the systolic activity. In addition to having effects on systolic activity, injection of saline, vagal stimulation, and sympathetic \"denervation\" always activated the receptors during filling. Our results indicate that: (1) the systolic discharge of type A receptors is a function of the active tension developed by atrial muscle during contraction; and (2) the pattern of discharge of the receptors during the atrial cycle depends on both the degree of atrial distention and the state and extent of contraction.", "contents": "Mechanical stimuli exciting type A atrial vagal receptors in the cat. The activity of type A right atrial vagal receptors was recorded from the right cervical vagus in cats anesthetized with sodium pentobarbital, immobilized with gallamine, and with their chests open. Nerve impulses initiated by receptor activation were recorded simultaneously with instantaneous right atrial pressure and dimensional changes under various hemodynamic conditions. Atrial volume changes induced by infusion of saline, bleeding, and occlusion of the inferior vena cava did not alter consistently the systolic activity of the receptors. Electrical stimulation of the right stellate ganglion significantly increased the frequency of discharge during systole, whereas electrical stimulation of the left thoracic vagus significantly reduced the frequency of discharge. These inotropic interventions produced similar effects when the heart was paced at a fixed rate. Pacing the right atrial appendage increased the systolic discharge of the receptors only when at high rates the atrium contracted against closed atrioventricular valves. To investigate the influence of tonic efferent sympathetic activity on spontaneous receptor discharge, three receptors were studied before and after bilateral surgical stellectomy, and in cats with their chest closed three receptors were studied before and after infusion of propranolol. Both of these interventions markedly reduced the systolic activity. In addition to having effects on systolic activity, injection of saline, vagal stimulation, and sympathetic \"denervation\" always activated the receptors during filling. Our results indicate that: (1) the systolic discharge of type A receptors is a function of the active tension developed by atrial muscle during contraction; and (2) the pattern of discharge of the receptors during the atrial cycle depends on both the degree of atrial distention and the state and extent of contraction."} {"id": "PMID:1269080", "title": "Substructure of intercellular junctions in freeze-fractured alveolar-capillary membranes of mouse lung.", "content": "The purpose of this study was to examine by freeze-fracture the ultrastructure of intercellular junctions between mouse pulmonary endothelial and epithelial cells, and to relate this fine structure to that deduced from previous physiological and ultrastructural studies using tracer techniques. Junctions between capillary endothelial cells consist of one to three interconnected rows of particles which show occasional discontinuities. Small gap junctions are associated with these rows of particles in the arteriolar end of the capillary bed. At the venular end, the junctions consist of low profile ridges on the protoplasmic fracture (PF) face or complimentary grooves on the exoplasmic fracture (EF) face some of which have a sparse number of associated particles. The vascular junctions are similar to those of vessels in rat omentum and mesentery, and resemble \"leaky\" junctions described in renal proximal convoluted tubular cells. Tight junctions (zonulae occludentes) between type I pneumocytes or between types I and II pneumocytes consist of a band of interconnecting ridges on the PF face and complimentary interconnecting grooves on the EF face. These continuous epithelial junctions have a structure that is typical of tight occluding junctions. Occasionally zonulae occludentes between type I and type II pneumocytes are discontinuous; this may be the result of cell translocation as pneumocytes are shed into the alveolus. Intravascular perfusion fixation at high pressure (140 cm H2O) had no discernible effect on the structure of endothelial or epithelial junctions. The appearance in our study of freeze-fractured pulmonary endothelial and epithelial junctions reveals clearly the physical basis for the results of ultrastructural tracer and physiological studies which have suggested that it is the alveolar epithelium rather than the endothelium that is the chief permeability barrier to small, water-soluble molecules.", "contents": "Substructure of intercellular junctions in freeze-fractured alveolar-capillary membranes of mouse lung. The purpose of this study was to examine by freeze-fracture the ultrastructure of intercellular junctions between mouse pulmonary endothelial and epithelial cells, and to relate this fine structure to that deduced from previous physiological and ultrastructural studies using tracer techniques. Junctions between capillary endothelial cells consist of one to three interconnected rows of particles which show occasional discontinuities. Small gap junctions are associated with these rows of particles in the arteriolar end of the capillary bed. At the venular end, the junctions consist of low profile ridges on the protoplasmic fracture (PF) face or complimentary grooves on the exoplasmic fracture (EF) face some of which have a sparse number of associated particles. The vascular junctions are similar to those of vessels in rat omentum and mesentery, and resemble \"leaky\" junctions described in renal proximal convoluted tubular cells. Tight junctions (zonulae occludentes) between type I pneumocytes or between types I and II pneumocytes consist of a band of interconnecting ridges on the PF face and complimentary interconnecting grooves on the EF face. These continuous epithelial junctions have a structure that is typical of tight occluding junctions. Occasionally zonulae occludentes between type I and type II pneumocytes are discontinuous; this may be the result of cell translocation as pneumocytes are shed into the alveolus. Intravascular perfusion fixation at high pressure (140 cm H2O) had no discernible effect on the structure of endothelial or epithelial junctions. The appearance in our study of freeze-fractured pulmonary endothelial and epithelial junctions reveals clearly the physical basis for the results of ultrastructural tracer and physiological studies which have suggested that it is the alveolar epithelium rather than the endothelium that is the chief permeability barrier to small, water-soluble molecules."} {"id": "PMID:1269081", "title": "Altered venous function in hypertensive rats.", "content": "The vascular beds of the upper or lower body of rats were perfused through the aorta with oxygenated Krebs-Ringer solution containing dextran (7 g/100 ml), at 37 degrees C. Perfusion was stopped every 10 minutes, and the pressure rise in the jugular or the femoral vein was recorded during rapid infusion (15.3-90.0 ml/min) of Krebs-Ringer solution into the inferior vena cava. The following groups of rats were studied: (1) six male genetically hypertensive rats (GHR), 9-11 months old, New Zealand strain; (2) seven female GHR, 5-6 months old, New Zealand strain; (3) eight male spontaneously hypertensive rats (SHR), 4 months old, Okamoto strain; (4) five male rats with two-kidney Goldblatt hypertension (2-KGH), 30 days postclipping; (5) seven male 2-KGH rats, 65 days postclipping; (6) eight male rats with one-kidney Goldblatt hypertension (1-KGH), 40 days postclipping; (7) weight- and sex-matched normotensive control rats of the appropriate strain; and (8) weight- and sex-matched two-kidney and one-kidney, sham-clipped normotensive rats. Preliminary studies showed that rapid infusion into the venous circulation fills the veins, but there is no entry of fluid into the arterial side of the circulation. Compared to controls, the venous pressure-volume curves of GHR (male and female), SHR, 1-KGH rats and 2-KGH rats, 65 (but not 30) days postclipping, were shifted toward the pressure axis (P less than 0.05). The shift of the venous pressure-volume curves persisted following the reduction of vasoconstrictor tone by killing the rats or by the administration of sodium nitroprusside (0.1 mg/ml perfusate), or by both. The findings suggest decreased venous capacity in hypertensive rats.", "contents": "Altered venous function in hypertensive rats. The vascular beds of the upper or lower body of rats were perfused through the aorta with oxygenated Krebs-Ringer solution containing dextran (7 g/100 ml), at 37 degrees C. Perfusion was stopped every 10 minutes, and the pressure rise in the jugular or the femoral vein was recorded during rapid infusion (15.3-90.0 ml/min) of Krebs-Ringer solution into the inferior vena cava. The following groups of rats were studied: (1) six male genetically hypertensive rats (GHR), 9-11 months old, New Zealand strain; (2) seven female GHR, 5-6 months old, New Zealand strain; (3) eight male spontaneously hypertensive rats (SHR), 4 months old, Okamoto strain; (4) five male rats with two-kidney Goldblatt hypertension (2-KGH), 30 days postclipping; (5) seven male 2-KGH rats, 65 days postclipping; (6) eight male rats with one-kidney Goldblatt hypertension (1-KGH), 40 days postclipping; (7) weight- and sex-matched normotensive control rats of the appropriate strain; and (8) weight- and sex-matched two-kidney and one-kidney, sham-clipped normotensive rats. Preliminary studies showed that rapid infusion into the venous circulation fills the veins, but there is no entry of fluid into the arterial side of the circulation. Compared to controls, the venous pressure-volume curves of GHR (male and female), SHR, 1-KGH rats and 2-KGH rats, 65 (but not 30) days postclipping, were shifted toward the pressure axis (P less than 0.05). The shift of the venous pressure-volume curves persisted following the reduction of vasoconstrictor tone by killing the rats or by the administration of sodium nitroprusside (0.1 mg/ml perfusate), or by both. The findings suggest decreased venous capacity in hypertensive rats."} {"id": "PMID:1269082", "title": "Regional myocardial blood flow during acute myocardial infarction in the conscious dog.", "content": "Regional myocardial blood flow was studied in the conscious dog at periods of 5 minutes to 4 days after occlusion of a major branch of the left coronary artery. Dogs were instrumented with aortic electromagnetic flow probes, occlusive cuffs on either the anterior descending or circumflex branch of the left coronary artery, and a left atrial Silastic catheter for injection of microspheres (15 +/- 5 mum) labeled with either 85Sr, 141Ce, or 51Cr. Microspheres were injected into 25 fully conscious dogs during three of the following time periods: control preocclusion and 0.1, 2, 6, 24, or 96 hours postocclusion. In the conscious dog, before occlusion, the endocardial half of the left ventricular myocardium received 28% more blood flow than the epicardial half. After sudden occlusion of a coronary artery branch, there was a marked reduction in blood flow as well as an alteration in distribution of blood flow within the ischemic tissue; blood flow was most severly reduced in the subendocardial center of the ischemic region, less so in the epicardial ischemic region, and least reduced in the marginal region of the infarct. Blood flow was increased to the nonischemic tissue. There was no change in this pattern of reduced blood flow by 6 hours postocclusion, but by 24 hours, flow was moderately increased to all areas except the central subendocardial core, and was further increased at 96 hours. Blood flow to the endocardial half of the left ventricular myocardium averaged 63 ml/100 g per min during the control period, was reduced to 12-18 ml/100 g per min at 0.1-6 hours in the ischemic region, increased to 29 ml/100 g per min at 24 hours, and to 48 ml/100 g per min by 96 hours. These findings indicate that there is a reversal of the flow ratio within ischemic myocardium with relative under-perfusion of the endocardial half of the wall, which is not corrected by 4 days. There is a modest increase of collateral blood flow to ischemic tissue by 24 hours and this increase is considerably augmented by 96 hours, apparently as a result of the growth and enlargement of collateral vessels.", "contents": "Regional myocardial blood flow during acute myocardial infarction in the conscious dog. Regional myocardial blood flow was studied in the conscious dog at periods of 5 minutes to 4 days after occlusion of a major branch of the left coronary artery. Dogs were instrumented with aortic electromagnetic flow probes, occlusive cuffs on either the anterior descending or circumflex branch of the left coronary artery, and a left atrial Silastic catheter for injection of microspheres (15 +/- 5 mum) labeled with either 85Sr, 141Ce, or 51Cr. Microspheres were injected into 25 fully conscious dogs during three of the following time periods: control preocclusion and 0.1, 2, 6, 24, or 96 hours postocclusion. In the conscious dog, before occlusion, the endocardial half of the left ventricular myocardium received 28% more blood flow than the epicardial half. After sudden occlusion of a coronary artery branch, there was a marked reduction in blood flow as well as an alteration in distribution of blood flow within the ischemic tissue; blood flow was most severly reduced in the subendocardial center of the ischemic region, less so in the epicardial ischemic region, and least reduced in the marginal region of the infarct. Blood flow was increased to the nonischemic tissue. There was no change in this pattern of reduced blood flow by 6 hours postocclusion, but by 24 hours, flow was moderately increased to all areas except the central subendocardial core, and was further increased at 96 hours. Blood flow to the endocardial half of the left ventricular myocardium averaged 63 ml/100 g per min during the control period, was reduced to 12-18 ml/100 g per min at 0.1-6 hours in the ischemic region, increased to 29 ml/100 g per min at 24 hours, and to 48 ml/100 g per min by 96 hours. These findings indicate that there is a reversal of the flow ratio within ischemic myocardium with relative under-perfusion of the endocardial half of the wall, which is not corrected by 4 days. There is a modest increase of collateral blood flow to ischemic tissue by 24 hours and this increase is considerably augmented by 96 hours, apparently as a result of the growth and enlargement of collateral vessels."} {"id": "PMID:1269083", "title": "Relationship between blood flow to ischemic regions and extent of myocardial infarction. Serial measurement of blood flow to ischemic regions in dogs.", "content": "This study was designed to measure early sequential changes in blood flow to ischemic regions after acute coronary occlusion and to determine the relationship between blood flow and the extent of subsequent myocardial infarction. Initial studies were carried out on five dogs which verified using radioisotope-labeled microspheres, 7-10 mum in diameter, to measure changes in blood flow in small myocardial regions after acute coronary artery occlusions. Studies then were carried out on 11 awake dogs chronically prepared with dwelling catheters in the aorta and left atrium and occluders on the left circumflex coronary artery. Microspheres were injected via the left atrial catheter 45 seconds and 2, 6, and 24 hours after complete circumflex coronary occlusion. Six days later myocardial blood flow and the extent of histological infarction were determined for multiple samples from four transmural layers of the entire ischemic zone. Average blood flow to the circumflex region was 0.25 +/- 0.03 (SE), 0.39 +/- 0.05, and 0.53 +/- 0.07 ml/min per g at 45 seconds, and 2, 6, and 24 hours, respectively. When samples from each transmuarl layer were grouped according to increasing ranges of blood flow, the extent of infarction in each layer was inversely related to blood flow. When samples in the same range of blood flow were compared, the extent of infarction in endocardial samples exceeded that in epicardial samples. These data indicate that the relationship between a given measurement of regional blood flow after acute coronary occlusion and the extent of subsequent myocardial infarction varies in different transmural layers and is a function of the time after occlusion that blood flow is measured.", "contents": "Relationship between blood flow to ischemic regions and extent of myocardial infarction. Serial measurement of blood flow to ischemic regions in dogs. This study was designed to measure early sequential changes in blood flow to ischemic regions after acute coronary occlusion and to determine the relationship between blood flow and the extent of subsequent myocardial infarction. Initial studies were carried out on five dogs which verified using radioisotope-labeled microspheres, 7-10 mum in diameter, to measure changes in blood flow in small myocardial regions after acute coronary artery occlusions. Studies then were carried out on 11 awake dogs chronically prepared with dwelling catheters in the aorta and left atrium and occluders on the left circumflex coronary artery. Microspheres were injected via the left atrial catheter 45 seconds and 2, 6, and 24 hours after complete circumflex coronary occlusion. Six days later myocardial blood flow and the extent of histological infarction were determined for multiple samples from four transmural layers of the entire ischemic zone. Average blood flow to the circumflex region was 0.25 +/- 0.03 (SE), 0.39 +/- 0.05, and 0.53 +/- 0.07 ml/min per g at 45 seconds, and 2, 6, and 24 hours, respectively. When samples from each transmuarl layer were grouped according to increasing ranges of blood flow, the extent of infarction in each layer was inversely related to blood flow. When samples in the same range of blood flow were compared, the extent of infarction in endocardial samples exceeded that in epicardial samples. These data indicate that the relationship between a given measurement of regional blood flow after acute coronary occlusion and the extent of subsequent myocardial infarction varies in different transmural layers and is a function of the time after occlusion that blood flow is measured."} {"id": "PMID:1269084", "title": "Depression of atrioventricular sensitivity in the dog by successive brief bursts of vagal stimulation.", "content": "When identical, successive single vagal stimulations, separated in time (T) by 2-60 seconds, are applied in the dog, the peak change in atrioventricular conduction time for the second stimulus, deltaAV2, is less than that of the first, deltaAV1, that is, the ratio deltaAV2/deltaAV1 less than 1.0 (the mean minimum deltaAV2/deltaAV1=0.52). It was further determined that at any one given T, the actual value of deltaAV2/deltaAV1 also was a function of the first stimulus amplitude. The same dependence of deltaAV2/deltaAV1 on the first stimulus amplitude was found when the amplitude was varied either by (1) changing the number of vagal fibers stimulated for both the first and second response, but at a constant AD (the delay in the cardiac cycle at which the stimulus was given), or (2) by stimulating the same number of fibers but changing AD for both the first and second response. Also the same characteristic of deltaAV2/deltaAV1 plotted vs. T was found either (1) when both the first and second responses were produced by stimulation of the same nerve, or (2) when stimulated of the nerve from one side produced the first response and the alternate side the second response. These data suggest that the reason for this deltaAV2/deltaAV1 time-dependent effect lies in changes in receptor responsiveness or in acetylcholine inactivation, but not in mechanisms purely internal to the nerve terminal associated with synthesis, storage, or release of acetylcholine.", "contents": "Depression of atrioventricular sensitivity in the dog by successive brief bursts of vagal stimulation. When identical, successive single vagal stimulations, separated in time (T) by 2-60 seconds, are applied in the dog, the peak change in atrioventricular conduction time for the second stimulus, deltaAV2, is less than that of the first, deltaAV1, that is, the ratio deltaAV2/deltaAV1 less than 1.0 (the mean minimum deltaAV2/deltaAV1=0.52). It was further determined that at any one given T, the actual value of deltaAV2/deltaAV1 also was a function of the first stimulus amplitude. The same dependence of deltaAV2/deltaAV1 on the first stimulus amplitude was found when the amplitude was varied either by (1) changing the number of vagal fibers stimulated for both the first and second response, but at a constant AD (the delay in the cardiac cycle at which the stimulus was given), or (2) by stimulating the same number of fibers but changing AD for both the first and second response. Also the same characteristic of deltaAV2/deltaAV1 plotted vs. T was found either (1) when both the first and second responses were produced by stimulation of the same nerve, or (2) when stimulated of the nerve from one side produced the first response and the alternate side the second response. These data suggest that the reason for this deltaAV2/deltaAV1 time-dependent effect lies in changes in receptor responsiveness or in acetylcholine inactivation, but not in mechanisms purely internal to the nerve terminal associated with synthesis, storage, or release of acetylcholine."} {"id": "PMID:1269086", "title": "Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle.", "content": "The observation that increased muscular activity leads to muscle hypertrophy is well known, but identification of the biochemical and physiological mechanisms by which this occurs remains an important problem. The hypothesis has been proposed that creatine, an end product of contraction, may be the chemical signal coupling increased muscular activity and increased contractile mass. Two muscle models have been used in experimental tests of this hypothesis: differentiating skeletal muscle cells in culture and the fetal mouse heart in organ culture. Using these culture models, it is possible to alter the intracellular creatine concentration and to measure the effect of increased creatine concentrations on the rates of synthesis and accumulation of both muscle-specific and nonspecific proteins. The results show that muscle-specific protein synthesis in both skeletal and cardiac muscle is selectively stimulated by creatine.", "contents": "Creatine and the control of muscle-specific protein synthesis in cardiac and skeletal muscle. The observation that increased muscular activity leads to muscle hypertrophy is well known, but identification of the biochemical and physiological mechanisms by which this occurs remains an important problem. The hypothesis has been proposed that creatine, an end product of contraction, may be the chemical signal coupling increased muscular activity and increased contractile mass. Two muscle models have been used in experimental tests of this hypothesis: differentiating skeletal muscle cells in culture and the fetal mouse heart in organ culture. Using these culture models, it is possible to alter the intracellular creatine concentration and to measure the effect of increased creatine concentrations on the rates of synthesis and accumulation of both muscle-specific and nonspecific proteins. The results show that muscle-specific protein synthesis in both skeletal and cardiac muscle is selectively stimulated by creatine."} {"id": "PMID:1269087", "title": "Effects of anoxia and ischemia on protein synthesis in perfused rat hearts.", "content": "The effect of ischemia on synthesis of myocardial proteins was investigated using a model of perfusion in which low levels of coronary flow were provided to paced hearts worked against a closed aortic outflow tract. These conditions rapidly produced ischemia and ventricular failure, as evidence by reduced coronary flow, increased left atrial pressure, and decreased pressure development. Protein synthesis was inhibited in a subsequent 1-hour period, during which a minimal coronary flow was maintained by retrograde perfusion. ATP, GTP, and creatinine phosphate were depleted in ischemic hearts and AMP accumulated. Production and accumulation of lactate within the tissue increased, whereas palmitate uptake was inhibited. The inhibition of protein synthesis was not associated with reduced levels of intracellular amino acids. During ischemia, decreased levels of ribosomal subunits as compared to paced or unpaced aerobic hearts suggested that peptide chain elongation was slow relative to initiation. Provision of insulin further reduced subunit levels but did not increase protein synthesis, suggesting that the hormone did not prevent inhibition of peptide chain elongation in energy-poor hearts.", "contents": "Effects of anoxia and ischemia on protein synthesis in perfused rat hearts. The effect of ischemia on synthesis of myocardial proteins was investigated using a model of perfusion in which low levels of coronary flow were provided to paced hearts worked against a closed aortic outflow tract. These conditions rapidly produced ischemia and ventricular failure, as evidence by reduced coronary flow, increased left atrial pressure, and decreased pressure development. Protein synthesis was inhibited in a subsequent 1-hour period, during which a minimal coronary flow was maintained by retrograde perfusion. ATP, GTP, and creatinine phosphate were depleted in ischemic hearts and AMP accumulated. Production and accumulation of lactate within the tissue increased, whereas palmitate uptake was inhibited. The inhibition of protein synthesis was not associated with reduced levels of intracellular amino acids. During ischemia, decreased levels of ribosomal subunits as compared to paced or unpaced aerobic hearts suggested that peptide chain elongation was slow relative to initiation. Provision of insulin further reduced subunit levels but did not increase protein synthesis, suggesting that the hormone did not prevent inhibition of peptide chain elongation in energy-poor hearts."} {"id": "PMID:1269088", "title": "Protein degradation in vivo and its regulation.", "content": "Protein degradation in mammalian cells may be regulated by size of the polypeptide subunit, susceptibility to degradation by proteases, alteration by mutational changes, and interaction with various ligands, including other proteins, lipids, cofactors, or metabolic intermediates. The pathway of degradation is not defined but appears to involve both lysosomal and nonlysosomal proteases.", "contents": "Protein degradation in vivo and its regulation. Protein degradation in mammalian cells may be regulated by size of the polypeptide subunit, susceptibility to degradation by proteases, alteration by mutational changes, and interaction with various ligands, including other proteins, lipids, cofactors, or metabolic intermediates. The pathway of degradation is not defined but appears to involve both lysosomal and nonlysosomal proteases."} {"id": "PMID:1269089", "title": "Hormonal control of cardiac protein and amino acid balance.", "content": "Isolated hearts of fetal mice in organ culture maintain active protein synthesis and protein degradation. Rates of degradation exceed rates of synthesis and as a result, the hearts are in state of negative protein balance as evidenced by net loss of protein and release of amino acids. Several hormones can alter amino acid metabolism and protein balance by altering synthesis or degradation, or both. In cultured fetal mouse hearts, insulin, the most extensively studies of the hormones increases the rate of protein synthesis by 13 +/- 3.7% and decreases the rate of protein degradation by 22 +/- 4.1% (p less than 0.01 for both). Together, these changes account for a 30-40% reduction in the loss of cardiac protein and in the release of phenylalanine from the heart. These changes are accompanied by a decrease of 21 +/- 2.7% in the total activity of the lysosomal proteinase cathepsin D. and by a reduction in the proportion of the enzyme that is present in the nonsedimentable fraction of the issue homogenate. This suggests that the possibility that insulin may function in part by altering lysosomal enzyme activity or availability, or both. The effects of insulin on protein degradation, amion acid release, and cathepsin D activity persist even when protein synthesis has been inhibited by cycloheximide. These results suggest that insulin plays an important role in the control of cardiac protein synthesis and degradation.", "contents": "Hormonal control of cardiac protein and amino acid balance. Isolated hearts of fetal mice in organ culture maintain active protein synthesis and protein degradation. Rates of degradation exceed rates of synthesis and as a result, the hearts are in state of negative protein balance as evidenced by net loss of protein and release of amino acids. Several hormones can alter amino acid metabolism and protein balance by altering synthesis or degradation, or both. In cultured fetal mouse hearts, insulin, the most extensively studies of the hormones increases the rate of protein synthesis by 13 +/- 3.7% and decreases the rate of protein degradation by 22 +/- 4.1% (p less than 0.01 for both). Together, these changes account for a 30-40% reduction in the loss of cardiac protein and in the release of phenylalanine from the heart. These changes are accompanied by a decrease of 21 +/- 2.7% in the total activity of the lysosomal proteinase cathepsin D. and by a reduction in the proportion of the enzyme that is present in the nonsedimentable fraction of the issue homogenate. This suggests that the possibility that insulin may function in part by altering lysosomal enzyme activity or availability, or both. The effects of insulin on protein degradation, amion acid release, and cathepsin D activity persist even when protein synthesis has been inhibited by cycloheximide. These results suggest that insulin plays an important role in the control of cardiac protein synthesis and degradation."} {"id": "PMID:1269090", "title": "The role of acyltransferases in fatty acid utilization.", "content": "Glycerophosphate and carnitine as competing acyl acceptors and the oxidation of different long chain acylcarnitines in isolated mitochondria have been investigated. In the presence of low concentrations of palmitate, glycerophosphate is the preferred acyl acceptor in isolated liver mitochondria, indicating that the glycerophosphate acyltransferase has a lower Michaelis constant (Km) for palmityl-CoA than has the carnitine palmityltransferase. Liver mitochondria from starved rats make more palmitylcarnitine and less palmitylglycerophosphate than do mitochondria from starved/refed rats. In heart mitochondria glycerophosphate has less effect on palmitylcarnitine formation because of glycerophosphate acyltransferase activity is lower and the carnitine palmityltransferase activity is higher in liver mitochondria. Carnitine esters of C22 fatty acids, especially erucic acid (22:1omega9,cis) are more slowly oxidized compared to palmitylcarnitine in heart than in liver mitochondria. They also inhibit palmitylcarnitine oxidation. The inhibition is relatively stronger in heart than in liver mitochondria. These observations are discussed in relation to organ differences in the utilization of fatty acids.", "contents": "The role of acyltransferases in fatty acid utilization. Glycerophosphate and carnitine as competing acyl acceptors and the oxidation of different long chain acylcarnitines in isolated mitochondria have been investigated. In the presence of low concentrations of palmitate, glycerophosphate is the preferred acyl acceptor in isolated liver mitochondria, indicating that the glycerophosphate acyltransferase has a lower Michaelis constant (Km) for palmityl-CoA than has the carnitine palmityltransferase. Liver mitochondria from starved rats make more palmitylcarnitine and less palmitylglycerophosphate than do mitochondria from starved/refed rats. In heart mitochondria glycerophosphate has less effect on palmitylcarnitine formation because of glycerophosphate acyltransferase activity is lower and the carnitine palmityltransferase activity is higher in liver mitochondria. Carnitine esters of C22 fatty acids, especially erucic acid (22:1omega9,cis) are more slowly oxidized compared to palmitylcarnitine in heart than in liver mitochondria. They also inhibit palmitylcarnitine oxidation. The inhibition is relatively stronger in heart than in liver mitochondria. These observations are discussed in relation to organ differences in the utilization of fatty acids."} {"id": "PMID:1269091", "title": "Coordination of citric acid cycle activity with electron transport flux.", "content": "Feedback control between flux through the phosphorylating electron transport chain and the coordination of flux through individual steps of the citric acid cycle have been investigated under a number of different conditions of substrate availability and workloads in the isolated perfused rat heart. The transition from substrate-free perfusion to perfusion with glucose and insulin with no change of workload was associated with increases in the pool sizes of citric acid cycle intermediates except for oxaloacetate, but with an initial imbalance of flux through individual steps in the cycle and transport of anions of the malate-aspartate cycle across the mitochondrial membrane. Flux through citrate synthase initially increased while that through alpha-ketoglutarate dehydrogenase decreased. Of the components of the malate-aspartate cycle, flux through the malate-alpha-ketoglutarate exchange was increased prior to that through the glutamate-aspartate exchange and intramitochondrial aspartate aminotransferase. These changes can be accounted for on the basis of known kinetic controls of the enzyme and transport steps in response to increased pyruvate, acetyl-CoA, and NADH delivery at an approximately constant rate of ATP turnover.", "contents": "Coordination of citric acid cycle activity with electron transport flux. Feedback control between flux through the phosphorylating electron transport chain and the coordination of flux through individual steps of the citric acid cycle have been investigated under a number of different conditions of substrate availability and workloads in the isolated perfused rat heart. The transition from substrate-free perfusion to perfusion with glucose and insulin with no change of workload was associated with increases in the pool sizes of citric acid cycle intermediates except for oxaloacetate, but with an initial imbalance of flux through individual steps in the cycle and transport of anions of the malate-aspartate cycle across the mitochondrial membrane. Flux through citrate synthase initially increased while that through alpha-ketoglutarate dehydrogenase decreased. Of the components of the malate-aspartate cycle, flux through the malate-alpha-ketoglutarate exchange was increased prior to that through the glutamate-aspartate exchange and intramitochondrial aspartate aminotransferase. These changes can be accounted for on the basis of known kinetic controls of the enzyme and transport steps in response to increased pyruvate, acetyl-CoA, and NADH delivery at an approximately constant rate of ATP turnover."} {"id": "PMID:1269092", "title": "Control of energy production in myocardial ischemia.", "content": "Long chain fatty acyl-CoA esters are potent in vitro and in vivo inhibitors of adenine nucleotide translocation in heart mitochondria. Within a short time following production of myocardial ischemia, the dog heart exhibits an increased concentration of long chain acyl-CoA esters associated with a decrease in adenine nucleotide translocase activity. In contrast to liver, the tricarboxylate carrier system for citrate and phosphoenolpyruvate is rather low in heart mitochondria. Phosphoenolpyruvate-stimulated calcium egress from heart mitochondria may, therefore, result from transport of this anion on the adenine nucleotide translocase. During myocardial ischemia effective modulation of these metabolite trasnport systems are disrupted by accumulation of long chain acyl-CoA esters which leads to a decrease in the overall energy charge of the cell.", "contents": "Control of energy production in myocardial ischemia. Long chain fatty acyl-CoA esters are potent in vitro and in vivo inhibitors of adenine nucleotide translocation in heart mitochondria. Within a short time following production of myocardial ischemia, the dog heart exhibits an increased concentration of long chain acyl-CoA esters associated with a decrease in adenine nucleotide translocase activity. In contrast to liver, the tricarboxylate carrier system for citrate and phosphoenolpyruvate is rather low in heart mitochondria. Phosphoenolpyruvate-stimulated calcium egress from heart mitochondria may, therefore, result from transport of this anion on the adenine nucleotide translocase. During myocardial ischemia effective modulation of these metabolite trasnport systems are disrupted by accumulation of long chain acyl-CoA esters which leads to a decrease in the overall energy charge of the cell."} {"id": "PMID:1269093", "title": "Mitochondrial structure and function in acute myocardial ischemic injury.", "content": "Changes in both the structure and function of mitochondria occur in the dog heart as a consequence of severe ischemia produced by acute coronary occlusion. Brief periods of severe ischemia (reversible injury) produced no significant change in mitochondrial ultrastructure and no defects in pyruvate or succinate metabolism. However, periods of ischemia of 40-60 minutes' duration (irreversible injury) produced striking structural changes including swelling, an increase in matrix space, disorganization of cristae, and the appearance of amorphous matrix densities. After 60 minutes of severe ischemia, one or more amorphous densities were present in each mitochondrial profile. These osmiophilic structures contained lipid but have not been characterized further. Their presence was typical of the irreversible state. Mitochondria of irreversibly injured cells were fragile, and consequently were more difficult to isolate than mitochondria of control tissue. Furthermore, after isolation from tissue injured by 60 minutes of ischemia, they showed markedly defective function.", "contents": "Mitochondrial structure and function in acute myocardial ischemic injury. Changes in both the structure and function of mitochondria occur in the dog heart as a consequence of severe ischemia produced by acute coronary occlusion. Brief periods of severe ischemia (reversible injury) produced no significant change in mitochondrial ultrastructure and no defects in pyruvate or succinate metabolism. However, periods of ischemia of 40-60 minutes' duration (irreversible injury) produced striking structural changes including swelling, an increase in matrix space, disorganization of cristae, and the appearance of amorphous matrix densities. After 60 minutes of severe ischemia, one or more amorphous densities were present in each mitochondrial profile. These osmiophilic structures contained lipid but have not been characterized further. Their presence was typical of the irreversible state. Mitochondria of irreversibly injured cells were fragile, and consequently were more difficult to isolate than mitochondria of control tissue. Furthermore, after isolation from tissue injured by 60 minutes of ischemia, they showed markedly defective function."} {"id": "PMID:1269094", "title": "Considerations in the use of biochemical markers of ischemic injury.", "content": "Results of estimation of infarct size with a selected biochemical marker in blood, creatine phosphokinase (CPK), have suggested that infarct size is an important determinant of prognosis, impaired ventricular function, early ventricular dysrhythmia, and the severity of clinical manifestations. Estimates based on serial changes in serum CPK activity have correlated with morphological estimates and have been employed to evaluate therapeutic interventions. Improved estimates with any biochemical marker require exclusion of noncardiac sources of the marker and characterization of the influence of physiological alterations on parameters in empirical or physiologically based mathematical models utilized. Use of MB CPK instead of total CPK therefore improves enzymatic estimates when infarction is accompanied by release of noncardiac CPK into the circulation. Preliminary results with physiologically based models of CPK release from the infarct and its disappearance from the circulation suggest that release may be diffusion-limited and that the CPK disappearance rate is relatively uninfluenced by profound hemodynamic derangements or myocardial infarctions per se. The substantial inactivation of CPK in lymph in vitro and in situ underscores the importance of defining factors influencing the proportion of a biochemical marker depleted from necrotic myocardium appearing in blood, since the proportion is one parameter used in models employed to quantitatively estimate irreversible ischemic injury.", "contents": "Considerations in the use of biochemical markers of ischemic injury. Results of estimation of infarct size with a selected biochemical marker in blood, creatine phosphokinase (CPK), have suggested that infarct size is an important determinant of prognosis, impaired ventricular function, early ventricular dysrhythmia, and the severity of clinical manifestations. Estimates based on serial changes in serum CPK activity have correlated with morphological estimates and have been employed to evaluate therapeutic interventions. Improved estimates with any biochemical marker require exclusion of noncardiac sources of the marker and characterization of the influence of physiological alterations on parameters in empirical or physiologically based mathematical models utilized. Use of MB CPK instead of total CPK therefore improves enzymatic estimates when infarction is accompanied by release of noncardiac CPK into the circulation. Preliminary results with physiologically based models of CPK release from the infarct and its disappearance from the circulation suggest that release may be diffusion-limited and that the CPK disappearance rate is relatively uninfluenced by profound hemodynamic derangements or myocardial infarctions per se. The substantial inactivation of CPK in lymph in vitro and in situ underscores the importance of defining factors influencing the proportion of a biochemical marker depleted from necrotic myocardium appearing in blood, since the proportion is one parameter used in models employed to quantitatively estimate irreversible ischemic injury."} {"id": "PMID:1269096", "title": "Combined effects of rate membrane potential, and drugs on maximum rate of rise (Vmax) of action potential upstroke of guinea pig papillary muscle.", "content": "We studied the effect of increasing the rate of stimulation on the maximum rate of rise of the action potential upstroke (Vmax) in guinea pig papillary muscles at various resting membrane potentials and after the addition of quinidine and lidocaine to the perfusate. Increasing rate caused a decrease in Vmax due to interaction of three factors: (1) a metabolic factor, presumably resetting of the Na-K pump, which caused a decrease in Vmax at all levels of resting potential between -90 and -60 mV, (2) a transient decrease in resting potential which influenced Vmax when the resting potential was less negative than approximately -80 mV, and (3) the recovery characteristics of Vmax which contributed to the decrease in this variable when rate was faster than 5/sec. As a result of these factors the steady state curve relating membrane potential to Vmax was itself rate-dependent. Lidocaine and quinidine exaggerated the rate-dependent decrease in Vmax; however, their effects differed. The effect of quinidine was consistent with its known depressant effect on the Na-K pump. The lidocaine effect was consistent with a slowing of recovery of Vmax. Our results help to explain the effects of an increase in rate on Vmax and conduction velocity in normal, partially depolarized, and drug-treated fibers", "contents": "Combined effects of rate membrane potential, and drugs on maximum rate of rise (Vmax) of action potential upstroke of guinea pig papillary muscle. We studied the effect of increasing the rate of stimulation on the maximum rate of rise of the action potential upstroke (Vmax) in guinea pig papillary muscles at various resting membrane potentials and after the addition of quinidine and lidocaine to the perfusate. Increasing rate caused a decrease in Vmax due to interaction of three factors: (1) a metabolic factor, presumably resetting of the Na-K pump, which caused a decrease in Vmax at all levels of resting potential between -90 and -60 mV, (2) a transient decrease in resting potential which influenced Vmax when the resting potential was less negative than approximately -80 mV, and (3) the recovery characteristics of Vmax which contributed to the decrease in this variable when rate was faster than 5/sec. As a result of these factors the steady state curve relating membrane potential to Vmax was itself rate-dependent. Lidocaine and quinidine exaggerated the rate-dependent decrease in Vmax; however, their effects differed. The effect of quinidine was consistent with its known depressant effect on the Na-K pump. The lidocaine effect was consistent with a slowing of recovery of Vmax. Our results help to explain the effects of an increase in rate on Vmax and conduction velocity in normal, partially depolarized, and drug-treated fibers"} {"id": "PMID:1269097", "title": "Relation between plasma renin activity, angiotensin, and aldosterone and blood pressure in mild untreated hypertension.", "content": "Plasma renin activity, arterial and venous angiotensin II (A II), plasma aldosterone, and sodium excretion were measured in a group of 101 patients with mild essential hypertension. For the total hour; arterial A II was 5.2 +/- 1.0 pg/ml; venous A II was 4.2 +/- 0.6 pg/ml; and plasma aldosterone was 5.0 +/- 0.45 ng/100 ml. All values were lower corresponding values for normal subjects on a high salt intake despite the fact that salt intake in the normal subjects exceeded that for the hypertensive group more than 3-fold. Moreover, when the range of diastolic blood pressure up to 114 mm Hg was divided into three successive class intervals of increasing severity, there was a negative correlation between diastolic blood pressure and both PRA and plasma aldosterone. Arterial A II showed an anomalous increase in the class interval 105-114 mm Hg, despite the fact that this group exhibited the lowest level of PRA. At diastolic blood pressures above 114 mm Hg, the PRA appears to rise again. The anomalous increase in arterial A II in the presence of marked suppression of PRA is consistent with the presence of a renin activator or accelerator factor in hypertensive plasma as postulated by others. It also identifies a possible mechanism whereby even small increases in PRA could exert an adverse effect on the hypertensive state.", "contents": "Relation between plasma renin activity, angiotensin, and aldosterone and blood pressure in mild untreated hypertension. Plasma renin activity, arterial and venous angiotensin II (A II), plasma aldosterone, and sodium excretion were measured in a group of 101 patients with mild essential hypertension. For the total hour; arterial A II was 5.2 +/- 1.0 pg/ml; venous A II was 4.2 +/- 0.6 pg/ml; and plasma aldosterone was 5.0 +/- 0.45 ng/100 ml. All values were lower corresponding values for normal subjects on a high salt intake despite the fact that salt intake in the normal subjects exceeded that for the hypertensive group more than 3-fold. Moreover, when the range of diastolic blood pressure up to 114 mm Hg was divided into three successive class intervals of increasing severity, there was a negative correlation between diastolic blood pressure and both PRA and plasma aldosterone. Arterial A II showed an anomalous increase in the class interval 105-114 mm Hg, despite the fact that this group exhibited the lowest level of PRA. At diastolic blood pressures above 114 mm Hg, the PRA appears to rise again. The anomalous increase in arterial A II in the presence of marked suppression of PRA is consistent with the presence of a renin activator or accelerator factor in hypertensive plasma as postulated by others. It also identifies a possible mechanism whereby even small increases in PRA could exert an adverse effect on the hypertensive state."} {"id": "PMID:1269098", "title": "Plasma renin activity during exercise in the dog.", "content": "Previous workers have suggested that a rise in plasma renin activity (PRA) may mediate some of the hemodynamic changes associated with exercise. To test this hypothesis in nine dogs chronically instrumented for measurement of aortic pressure (catheter) or cardiac output (ascending aorta electromagnetic flow probe) PRA was measured by radioimmunoassay in blood samples drawn before and during running on a level treadmill at 4-8 miles per hour. Exercise caused increases in heart rate from 96 +/- 5 (SE) to 186 +/- 7 beats/min, cardiac output from 2.8 +/- 0.3 to 6.2 +/- 0.6 liters/min, and mean aortic pressure from 115 +/- 5 to 132 +/- 5 mm Hg (P less than 0.01). Mean PRA was 6.6 +/- 0.7 (SE) ng of angiotensin 1/ml per 3 hours before and 7.6 +/- 1.2 ng Ang I during exercise, values that are not different statistically. Propranolol reduced PRA at rest from 8.6 +/- 1.1 to 5.9 +/- 1.1 ng Ang 1 (P less than 0.05), but there was no significant difference between resting and exercise levels, although the increments in heart rate, cardiac output, and mean aortic pressure were reduced. Standing on hindlimbs for 5 minutes did not cause a change in mean aortic pressure or PRA. However, administration of pentolinium reduced mean aortic pressure, and PRA rose from 6.0 +/- 1.1 to 9.8 +/- 1.5 ng Ang I. Exercise, with or without beta-adrenergic blockade, does not cause increased PRA in conscious dogs in which the renin-angiotensin system is normally responsive.", "contents": "Plasma renin activity during exercise in the dog. Previous workers have suggested that a rise in plasma renin activity (PRA) may mediate some of the hemodynamic changes associated with exercise. To test this hypothesis in nine dogs chronically instrumented for measurement of aortic pressure (catheter) or cardiac output (ascending aorta electromagnetic flow probe) PRA was measured by radioimmunoassay in blood samples drawn before and during running on a level treadmill at 4-8 miles per hour. Exercise caused increases in heart rate from 96 +/- 5 (SE) to 186 +/- 7 beats/min, cardiac output from 2.8 +/- 0.3 to 6.2 +/- 0.6 liters/min, and mean aortic pressure from 115 +/- 5 to 132 +/- 5 mm Hg (P less than 0.01). Mean PRA was 6.6 +/- 0.7 (SE) ng of angiotensin 1/ml per 3 hours before and 7.6 +/- 1.2 ng Ang I during exercise, values that are not different statistically. Propranolol reduced PRA at rest from 8.6 +/- 1.1 to 5.9 +/- 1.1 ng Ang 1 (P less than 0.05), but there was no significant difference between resting and exercise levels, although the increments in heart rate, cardiac output, and mean aortic pressure were reduced. Standing on hindlimbs for 5 minutes did not cause a change in mean aortic pressure or PRA. However, administration of pentolinium reduced mean aortic pressure, and PRA rose from 6.0 +/- 1.1 to 9.8 +/- 1.5 ng Ang I. Exercise, with or without beta-adrenergic blockade, does not cause increased PRA in conscious dogs in which the renin-angiotensin system is normally responsive."} {"id": "PMID:1269099", "title": "Arterial lesions in repeatedly bred spontaneously hypertensive rats.", "content": "Repeatedly bred male and female rats of many strains develop hyperglycemia, hyperlipidemia, hypertension, and arteriosclerosis spontaneously. The intensity of their arterial disease and related metabolic derangements appear to be related to their reproductive activity. Repeatedly bred spontaneously hypertensive rats (SHR) were found to have severe hypertension, hyperglycemia, hyperlipidemia, elevated creatine phosphokinase (CPK), serum glutamic oxaloacetic and glutamic pyruvic transaminase (SGOT, SGPT), and lactic dehydrogenase (LDH), as well as high circulating corticosterone levels. Despite these atherogenic metabolic derangements and their severe hypertension, the breeder SHR did not develop the severe, generalized arteriosclerosis found in other strains of breeder rats. Instead, the arterial lesions, consisting of intimal hyalinization and fibrosis, medial hypertrophy, and occlusion of the lumen, were found only in male breeder SHR and were confined to the intratubular arteries of the testes. It is suggested that the severe hypertension, genetic influences, or differences in hypothalamic-pituitary-adrenal-gonadal function in breeder SHR may not have been conducive to the development of arteriosclerosis in this particular strain of rats.", "contents": "Arterial lesions in repeatedly bred spontaneously hypertensive rats. Repeatedly bred male and female rats of many strains develop hyperglycemia, hyperlipidemia, hypertension, and arteriosclerosis spontaneously. The intensity of their arterial disease and related metabolic derangements appear to be related to their reproductive activity. Repeatedly bred spontaneously hypertensive rats (SHR) were found to have severe hypertension, hyperglycemia, hyperlipidemia, elevated creatine phosphokinase (CPK), serum glutamic oxaloacetic and glutamic pyruvic transaminase (SGOT, SGPT), and lactic dehydrogenase (LDH), as well as high circulating corticosterone levels. Despite these atherogenic metabolic derangements and their severe hypertension, the breeder SHR did not develop the severe, generalized arteriosclerosis found in other strains of breeder rats. Instead, the arterial lesions, consisting of intimal hyalinization and fibrosis, medial hypertrophy, and occlusion of the lumen, were found only in male breeder SHR and were confined to the intratubular arteries of the testes. It is suggested that the severe hypertension, genetic influences, or differences in hypothalamic-pituitary-adrenal-gonadal function in breeder SHR may not have been conducive to the development of arteriosclerosis in this particular strain of rats."} {"id": "PMID:1269100", "title": "The influence of combined intra-aortic balloon counterpulsation and hyperosomotic mannitol on regional myocardial blood flow in ischemic myocardium in the dog.", "content": "We investigated the combined effectiveness of intra-aortic balloon counterpulsation and hyperosmotic mannitol (25%) on regional myocardial blood flow during acute coronary insufficiency. Cardiac output and paced heart rate were held constant in chloralose-anesthetized dogs during right heart bypass. Acute coronary insufficiency was produced by ligation of the proximal left anterior descending coronary artery (LAD). Regional myocardial blood flow was measured using radioactive microspheres. Left ventricular end-diastolic pressure, mean aortic pressure, maximum left ventricular dp/dt, and hematocrit were unchanged by combined mannitol infusion and balloon pumping. Studies of combined treatment with balloon pumping and mannitol immediately after the second of two 13-minute consecutive reversible ligations of the LAD demonstrated that (1) collateral coronary blood flow increased 46% (P less than 0.02) in ischemic myocardium compared with mannitol infusion along during the first LAD ligation, and (2) collateral coronary blood flow increased 27% (P less than 0.05) in ischemic myocardium compared with balloon pumping along during the first LAD ligation. Studies in which combined treatment was delayed until 20 minutes after LAD ligation demonstrated that collateral coronary blood flow was elevated by 33% (P les than 0.05) in ischemic myocardium compared to control studies in which balloon pumping alone had no effect. The results suggest that the increase in collateral coronary blood flow was in part a result of an increased transmural pressure gradient produced by balloon diastolic augmentation and the ability of mannitol to reduce coronary vascular resistance in ischemic myocardium.", "contents": "The influence of combined intra-aortic balloon counterpulsation and hyperosomotic mannitol on regional myocardial blood flow in ischemic myocardium in the dog. We investigated the combined effectiveness of intra-aortic balloon counterpulsation and hyperosmotic mannitol (25%) on regional myocardial blood flow during acute coronary insufficiency. Cardiac output and paced heart rate were held constant in chloralose-anesthetized dogs during right heart bypass. Acute coronary insufficiency was produced by ligation of the proximal left anterior descending coronary artery (LAD). Regional myocardial blood flow was measured using radioactive microspheres. Left ventricular end-diastolic pressure, mean aortic pressure, maximum left ventricular dp/dt, and hematocrit were unchanged by combined mannitol infusion and balloon pumping. Studies of combined treatment with balloon pumping and mannitol immediately after the second of two 13-minute consecutive reversible ligations of the LAD demonstrated that (1) collateral coronary blood flow increased 46% (P less than 0.02) in ischemic myocardium compared with mannitol infusion along during the first LAD ligation, and (2) collateral coronary blood flow increased 27% (P less than 0.05) in ischemic myocardium compared with balloon pumping along during the first LAD ligation. Studies in which combined treatment was delayed until 20 minutes after LAD ligation demonstrated that collateral coronary blood flow was elevated by 33% (P les than 0.05) in ischemic myocardium compared to control studies in which balloon pumping alone had no effect. The results suggest that the increase in collateral coronary blood flow was in part a result of an increased transmural pressure gradient produced by balloon diastolic augmentation and the ability of mannitol to reduce coronary vascular resistance in ischemic myocardium."} {"id": "PMID:1269101", "title": "Turbulent blood flow in humans: its primary role in the production of ejection murmurs.", "content": "To clarify the postulate that turbulence may produce ejection murmurs, point velocity and sound were measured in the ascending aorta of 13 subjects: six with normal aortic valves, six with aortic valvular disease, and one with a Bjork-Shiley prosthetic aortic valve. Velocity was measured with a catheter-tip hot film anemometer probe, and sound was measured with a catheter-tip micromanometer. Ejection murmurs detected intra-arterially were always found to be associated with turbulent or highly disturbed flow. Conversely, in the absence of intra-arterial sound during ejection, only minor disturbances of flow were detected. A linear relation between the sound energy density and turbulent energy density was shown (r = 0.92) and a linear relation between the acoustic power output (sound intensity) and turbulent power supply (r = 0.87) also was shown. Studies in vitro of sound and point velocity distal to a porcine valve inserted within a cast of the aorta, which permitted precise centering of the transducers along the axis of flow, confirmed these observations. When the power generated by the turbulence exceeded 3 ergs/sec per cm2, the murmurs were audible at the chest wall. The clinical gradation of the intensity of the murmurs increased as the power of turbulence increased. In conclusion, in this study we have demonstrated a clear association between turbulent blood flow and systolic ejection murmurs.", "contents": "Turbulent blood flow in humans: its primary role in the production of ejection murmurs. To clarify the postulate that turbulence may produce ejection murmurs, point velocity and sound were measured in the ascending aorta of 13 subjects: six with normal aortic valves, six with aortic valvular disease, and one with a Bjork-Shiley prosthetic aortic valve. Velocity was measured with a catheter-tip hot film anemometer probe, and sound was measured with a catheter-tip micromanometer. Ejection murmurs detected intra-arterially were always found to be associated with turbulent or highly disturbed flow. Conversely, in the absence of intra-arterial sound during ejection, only minor disturbances of flow were detected. A linear relation between the sound energy density and turbulent energy density was shown (r = 0.92) and a linear relation between the acoustic power output (sound intensity) and turbulent power supply (r = 0.87) also was shown. Studies in vitro of sound and point velocity distal to a porcine valve inserted within a cast of the aorta, which permitted precise centering of the transducers along the axis of flow, confirmed these observations. When the power generated by the turbulence exceeded 3 ergs/sec per cm2, the murmurs were audible at the chest wall. The clinical gradation of the intensity of the murmurs increased as the power of turbulence increased. In conclusion, in this study we have demonstrated a clear association between turbulent blood flow and systolic ejection murmurs."} {"id": "PMID:1269102", "title": "Basal vascular tone in the kidney. Evaluation from the static pressure-flow relationship under normal autoregulation and at maximal dilation in the dog.", "content": "In conscious dogs static pressure-flow relationships (I-P curves) were obtained both for the normal autoregulating kidney vasculature and under conditions of maximal vasodilation induced by infusion of papaverine or acetylcholine into the renal artery. Concentration-response curves for the substances infused showed the typical S-shape. Control I-P curves exhibited an autoregulatory plateau; under maximal vasodilation the I-P curves were pressure-passive up to a perfusion pressure of 50 mm Hg, following a power function (1 = a-Pn) with an exponent greater than 1. Under the influence of acetylcholine, renal blood flow was significantly higher than under control conditions even at a perfusion pressure of 20 mm Hg. This indicates that there is an appreciable vascular tone even at a low pressure. The I-P curves under acetylcholine showed a break at about 50 mm Hg, above which the I-P curves were straight lines.", "contents": "Basal vascular tone in the kidney. Evaluation from the static pressure-flow relationship under normal autoregulation and at maximal dilation in the dog. In conscious dogs static pressure-flow relationships (I-P curves) were obtained both for the normal autoregulating kidney vasculature and under conditions of maximal vasodilation induced by infusion of papaverine or acetylcholine into the renal artery. Concentration-response curves for the substances infused showed the typical S-shape. Control I-P curves exhibited an autoregulatory plateau; under maximal vasodilation the I-P curves were pressure-passive up to a perfusion pressure of 50 mm Hg, following a power function (1 = a-Pn) with an exponent greater than 1. Under the influence of acetylcholine, renal blood flow was significantly higher than under control conditions even at a perfusion pressure of 20 mm Hg. This indicates that there is an appreciable vascular tone even at a low pressure. The I-P curves under acetylcholine showed a break at about 50 mm Hg, above which the I-P curves were straight lines."} {"id": "PMID:1269103", "title": "The effects of altered sodium balance and adrenergic blockade on renin release induced in rats by angiotensin antagonism.", "content": "Circulating angiotensin II is said to inhibit renin release by a direct, intrarenal action. This effect of angiotensin was studied indirectly using the selective angiotensin II antagonist saralasin (1Sar-8-Ala-angiotensin II) in conscious normal, sodium-depleted, and sodium-loaded rats. Saralasin caused a dose-related increase in plasma renin concentration (PRC) in normal and sodium-depleted rats, but had no effect on PRC in sodium-loaded animals. However, saralasin was 300 times more active in sodium-depleted rats than in normal rats. Saralasin caused hypotension and tachycardia in sodium-depleted rats, but not in normals. Propranolol inhibited saralasin-induced renin release by 99% in normal rats and by 75% in sodium-depleted rats but not alter the hypotensive effect of saralasin in the latter. Saralasin potentiated phentolamine-induced renin release, hypotension, and tachycardia in normal rats, and this potentiated renin release was blocked by propranolol. We conclude that a portion of saralasin-elicited renin release in sodium-depleted rats is mediated by hypotensive activation of the carotid baroreceptor reflex which increases sympathetic nervous activity in the kidney. However, in sodium-depleted rats saralasin induced a 42-fold increase in PRC, whereas an equipotent hypotensive dose of the vasodilator hydralazine caused only a 3.5-fold increase in PRC. Thus, we find that saralasin appears to have a selective effect on renin release over and above its hypotensive effect, which suggests an angiotensin-mediated, feedback mechanism inhibitory to renin release. Thus, we have come to the conclusion that for part of saralasin-induced renin release appears to be caused by disinhibition of angiotensin suppression of renin secretion. This \"short-loop\" feed-back mechanism is closely associated with intrarenal beta-adrenergic receptors, since propranolol impaired saralasin-induced renin release under all circumstances in our experiments.", "contents": "The effects of altered sodium balance and adrenergic blockade on renin release induced in rats by angiotensin antagonism. Circulating angiotensin II is said to inhibit renin release by a direct, intrarenal action. This effect of angiotensin was studied indirectly using the selective angiotensin II antagonist saralasin (1Sar-8-Ala-angiotensin II) in conscious normal, sodium-depleted, and sodium-loaded rats. Saralasin caused a dose-related increase in plasma renin concentration (PRC) in normal and sodium-depleted rats, but had no effect on PRC in sodium-loaded animals. However, saralasin was 300 times more active in sodium-depleted rats than in normal rats. Saralasin caused hypotension and tachycardia in sodium-depleted rats, but not in normals. Propranolol inhibited saralasin-induced renin release by 99% in normal rats and by 75% in sodium-depleted rats but not alter the hypotensive effect of saralasin in the latter. Saralasin potentiated phentolamine-induced renin release, hypotension, and tachycardia in normal rats, and this potentiated renin release was blocked by propranolol. We conclude that a portion of saralasin-elicited renin release in sodium-depleted rats is mediated by hypotensive activation of the carotid baroreceptor reflex which increases sympathetic nervous activity in the kidney. However, in sodium-depleted rats saralasin induced a 42-fold increase in PRC, whereas an equipotent hypotensive dose of the vasodilator hydralazine caused only a 3.5-fold increase in PRC. Thus, we find that saralasin appears to have a selective effect on renin release over and above its hypotensive effect, which suggests an angiotensin-mediated, feedback mechanism inhibitory to renin release. Thus, we have come to the conclusion that for part of saralasin-induced renin release appears to be caused by disinhibition of angiotensin suppression of renin secretion. This \"short-loop\" feed-back mechanism is closely associated with intrarenal beta-adrenergic receptors, since propranolol impaired saralasin-induced renin release under all circumstances in our experiments."} {"id": "PMID:1269104", "title": "Experimental myocardial infarction in the cat. I. Reversible decline in contractility of noninfarcted muscle.", "content": "The contractile state of the noninfarcted myocardium was examined in adult cats after myocardial infarction produced by ligation of several branches of the left coronary artery. At 2 days, 7 days, and 6 weeks after infarction, and after determination of intracardiac pressures, papillary muscles were exicised from the noninfarcted segment of the right ventricle and attached to a myograph for analysis of contractile function. One week after infarction there was a decline in actively developed force at Lmax, caused by a decrease in the rate of force development. In addition, the response to procedures that augment myocardial contractility, such as paired stimulation and increasing the frequency of electrical stimulation, was significantly depressed. Two days after infarction, changes were less significant, although similar in direction. Six weeks after infarction, developed force at Lmax had returned to normal values. The response to procedures augmenting contractility also had returned to normal. There appears to be a distinct, reversible loss of contractility in the remaining viable myocardium in the early phase after experimental infarction.", "contents": "Experimental myocardial infarction in the cat. I. Reversible decline in contractility of noninfarcted muscle. The contractile state of the noninfarcted myocardium was examined in adult cats after myocardial infarction produced by ligation of several branches of the left coronary artery. At 2 days, 7 days, and 6 weeks after infarction, and after determination of intracardiac pressures, papillary muscles were exicised from the noninfarcted segment of the right ventricle and attached to a myograph for analysis of contractile function. One week after infarction there was a decline in actively developed force at Lmax, caused by a decrease in the rate of force development. In addition, the response to procedures that augment myocardial contractility, such as paired stimulation and increasing the frequency of electrical stimulation, was significantly depressed. Two days after infarction, changes were less significant, although similar in direction. Six weeks after infarction, developed force at Lmax had returned to normal values. The response to procedures augmenting contractility also had returned to normal. There appears to be a distinct, reversible loss of contractility in the remaining viable myocardium in the early phase after experimental infarction."} {"id": "PMID:1269105", "title": "Modification of the flow-generating capability of the canine heart-lung compartment by the carotid sinus baroreceptor reflex.", "content": "To quantitatively understand how the carotid sinus baroreceptor reflex modifies the Starling curve (i.e., the aortic flow (AF)-mean right atrial pressure (MRAP) relationship), experiments were performed in closed-chest, naturally breathing, and anesthetized dogs before and after vagotomy. Mean aortic pressure (MAP) was fixed at approximately 100 mm Hg and the pressure in the isolated carotid sinus (ISP) was varied from 75 to 150 mm Hg in steps of 25 mm Hg. At each ISP, MRAP was slowly increased and decreased while measuring AF by a previously implanted electromagnetic flow probe. A family of AF-MRAP relation curves specified at the different ISP's were thus obtained. Third-order polynomials in MRAP and ISP adequately fit these curves. Whether the vagi were intact or cut, there was no significant difference between the AF-MRAP relation curves obtained at an ISP of 75 or 100 mm Hg. However, decreasing ISP from 125 to 100 mm Hg caused a 24% increase in AF, and increasing ISP to 150 mm Hg caused a 15% decrease in AF in the dogs with intact vagus nerves. For the vagotomized dogs, the same decrease or increase in ISP caused a 17% increase or a 21% decrease in AF, respectively. When MAP was allowed to change by the reflex, only insignificant changes in AF occurred. We conclude that the carotid sinus reflex significantly alters the flow-generating ability of the heart-lung compartment by as much as 40% but this becomes clearly observable only if the reflex change in aortic pressure is prevented.", "contents": "Modification of the flow-generating capability of the canine heart-lung compartment by the carotid sinus baroreceptor reflex. To quantitatively understand how the carotid sinus baroreceptor reflex modifies the Starling curve (i.e., the aortic flow (AF)-mean right atrial pressure (MRAP) relationship), experiments were performed in closed-chest, naturally breathing, and anesthetized dogs before and after vagotomy. Mean aortic pressure (MAP) was fixed at approximately 100 mm Hg and the pressure in the isolated carotid sinus (ISP) was varied from 75 to 150 mm Hg in steps of 25 mm Hg. At each ISP, MRAP was slowly increased and decreased while measuring AF by a previously implanted electromagnetic flow probe. A family of AF-MRAP relation curves specified at the different ISP's were thus obtained. Third-order polynomials in MRAP and ISP adequately fit these curves. Whether the vagi were intact or cut, there was no significant difference between the AF-MRAP relation curves obtained at an ISP of 75 or 100 mm Hg. However, decreasing ISP from 125 to 100 mm Hg caused a 24% increase in AF, and increasing ISP to 150 mm Hg caused a 15% decrease in AF in the dogs with intact vagus nerves. For the vagotomized dogs, the same decrease or increase in ISP caused a 17% increase or a 21% decrease in AF, respectively. When MAP was allowed to change by the reflex, only insignificant changes in AF occurred. We conclude that the carotid sinus reflex significantly alters the flow-generating ability of the heart-lung compartment by as much as 40% but this becomes clearly observable only if the reflex change in aortic pressure is prevented."} {"id": "PMID:1269106", "title": "Effects of chronic anemia on the coronary and coronary collateral vasculature in dogs.", "content": "We compared coronary resistances and collateral (retrograde) flows for a group of normal dogs (hematocrit 40) to values for a group of dogs with severe chronic anemia (hematocrit 17). We used an isolated heart preparation in which the vessels were maximally dilated by dipyridamole. All data were compared for a hematocrit of 40. The results showed a significant decrease in coronary resistances with anemia; average resistances (+/-SE) of the anterior descending, circumflex, and right coronary arteries of the control dogs were 1.04 +/- 0.09,0.74 +/- 0.01, and 2.63 +/- 0.17 mm Hg/[(ml/min)/100 g], respectively, and 0.6 +/- 0.04,0.41 +/- 0.05,and 1.17 +/- 0.15 for the anemic dogs. Average coronary collateral flows increased in anemia but statistical significance could not be shown. We conclude that increased vascularity is a long-term regulatory mechanism in response to a hypoxic stimulus.", "contents": "Effects of chronic anemia on the coronary and coronary collateral vasculature in dogs. We compared coronary resistances and collateral (retrograde) flows for a group of normal dogs (hematocrit 40) to values for a group of dogs with severe chronic anemia (hematocrit 17). We used an isolated heart preparation in which the vessels were maximally dilated by dipyridamole. All data were compared for a hematocrit of 40. The results showed a significant decrease in coronary resistances with anemia; average resistances (+/-SE) of the anterior descending, circumflex, and right coronary arteries of the control dogs were 1.04 +/- 0.09,0.74 +/- 0.01, and 2.63 +/- 0.17 mm Hg/[(ml/min)/100 g], respectively, and 0.6 +/- 0.04,0.41 +/- 0.05,and 1.17 +/- 0.15 for the anemic dogs. Average coronary collateral flows increased in anemia but statistical significance could not be shown. We conclude that increased vascularity is a long-term regulatory mechanism in response to a hypoxic stimulus."} {"id": "PMID:1269107", "title": "Regional cardiac prostaglandin release during myocardial ischemia in anesthetized dogs.", "content": "Cardiac prostaglandin release was studied in closed-chest dogs during acute coronary occlusion. Aortic and coronary sinus blood was obtained before, and at intervals after, balloon occlusion of the left anterior descending artery in seven dogs. Samples were assayed for prostaglandins F, E, and A by randioimmunoassay. All dogs demonstrated prostaglandin F release, Mean +/- SE postocclusion aortic levels were 0.26 +/- 0.01 ng/ml; coronary sinus levels were 0.67 +/- 0.01 ng/ml (P less than 0.001). In six dogs, prostaglandin E also was released. Mean postocclusion aortic levels were 0.24 +/- 0.01 ng/ml; coronary sinus, 0.44 +/- 0.01 ng/ml (P less than 0.001). There was no release of prostaglandin A. To examine the site of prostaglandin release, simultaneous samples from the aorta, the coronary sinus, and the great cardiac vein were obtained before and after left circumflex artery occlusion in six additional studies. The great cardiac vein drained effluent from nonischemic myocardium, whereas the coronary sinus drainage included blood from both ischemic and nonischemic zones. All six dogs demonstrated prostaglandin F release from the ischemic region. Mean postocclusion aortic prostaglandin F was 0.32 +/- 0.01 ng/ml. Coronary sinus prostaglandin F was 1.69 +/- 0.03 ng/ml (P less than 0.001), whereas the great cardiac vein level remained at 0.34 +/- 0.01 ng/ml (P greater than 0.05). Prostaglandin E was released from both ischemic and nonischemic regions. Mean aortic prostaglandin E was 0.21 +/- 0.01 ng/ml; great cardiac vein, 0.55 +/- 0.02 ng/ml (P less than 0.001); and coronary sinus, 1.07 +/- 0.04 ng/ml (P less than 0.001). These results have led us to conclude that the different local availability of prostaglandins E and F may influence the cardiac response to ischemia.", "contents": "Regional cardiac prostaglandin release during myocardial ischemia in anesthetized dogs. Cardiac prostaglandin release was studied in closed-chest dogs during acute coronary occlusion. Aortic and coronary sinus blood was obtained before, and at intervals after, balloon occlusion of the left anterior descending artery in seven dogs. Samples were assayed for prostaglandins F, E, and A by randioimmunoassay. All dogs demonstrated prostaglandin F release, Mean +/- SE postocclusion aortic levels were 0.26 +/- 0.01 ng/ml; coronary sinus levels were 0.67 +/- 0.01 ng/ml (P less than 0.001). In six dogs, prostaglandin E also was released. Mean postocclusion aortic levels were 0.24 +/- 0.01 ng/ml; coronary sinus, 0.44 +/- 0.01 ng/ml (P less than 0.001). There was no release of prostaglandin A. To examine the site of prostaglandin release, simultaneous samples from the aorta, the coronary sinus, and the great cardiac vein were obtained before and after left circumflex artery occlusion in six additional studies. The great cardiac vein drained effluent from nonischemic myocardium, whereas the coronary sinus drainage included blood from both ischemic and nonischemic zones. All six dogs demonstrated prostaglandin F release from the ischemic region. Mean postocclusion aortic prostaglandin F was 0.32 +/- 0.01 ng/ml. Coronary sinus prostaglandin F was 1.69 +/- 0.03 ng/ml (P less than 0.001), whereas the great cardiac vein level remained at 0.34 +/- 0.01 ng/ml (P greater than 0.05). Prostaglandin E was released from both ischemic and nonischemic regions. Mean aortic prostaglandin E was 0.21 +/- 0.01 ng/ml; great cardiac vein, 0.55 +/- 0.02 ng/ml (P less than 0.001); and coronary sinus, 1.07 +/- 0.04 ng/ml (P less than 0.001). These results have led us to conclude that the different local availability of prostaglandins E and F may influence the cardiac response to ischemia."} {"id": "PMID:1269108", "title": "Vessel caliber and branch-angle of human coronary artery branch-points.", "content": "Measurements were made of parent and branch vessel diameters and of the included angles of branch-points from postmortem human coronary arteriograms to determine the usefulness of theoretical equations predicting the relationships between parent and branch vessel caliber and between arterial caliber and branch-angle. The formulas were based on the concept that blood vessel size and arrangement provided for blood flow with minimum energy loss. Size relationships between parent vessel and its branches were determined for 42 left main and 53 other epicardial coronary artery branch-points in hearts with angiographically normal arteries. Left main coronary artery branch-points were studied in 68 hearts with various degrees of angiographically defined coronary artery disease. Measured diameters (D) of parent and branch vessels corresponded well to the theoretical formula: (DParent)3 = (DBranch1)3 + (DBranch2)3....,in angiographically normal coronary arteries. The exponent, on the average, is less with increasing grades of vascular disease for left main coronary artery branch-points. Mean area ratio, the sum of the cross-sectional area of the branches divided by the area of parent vessel, decreased with greater arteriographic disease. Area ratio varies with changes in the relative calibers of branch vessels. Fifty-seven branch-angles were determined by graphic analysis of postmortem biplane coronary arteriograms. No relationship could be found between branch-angle and vessel caliber. The included angle between branches varied from 32 degrees to 124 degrees without respect to relative or absolute vessel calibers. The results of these postmortem measurements on human coronary arteriogram suggest that coronary artery caliber may adjust to minimize energy loss at the branch-point but that branch-angle is determined by other factors. Restudy of arteriograms suggests that branch-angle may be determined by branch vessel destination.", "contents": "Vessel caliber and branch-angle of human coronary artery branch-points. Measurements were made of parent and branch vessel diameters and of the included angles of branch-points from postmortem human coronary arteriograms to determine the usefulness of theoretical equations predicting the relationships between parent and branch vessel caliber and between arterial caliber and branch-angle. The formulas were based on the concept that blood vessel size and arrangement provided for blood flow with minimum energy loss. Size relationships between parent vessel and its branches were determined for 42 left main and 53 other epicardial coronary artery branch-points in hearts with angiographically normal arteries. Left main coronary artery branch-points were studied in 68 hearts with various degrees of angiographically defined coronary artery disease. Measured diameters (D) of parent and branch vessels corresponded well to the theoretical formula: (DParent)3 = (DBranch1)3 + (DBranch2)3....,in angiographically normal coronary arteries. The exponent, on the average, is less with increasing grades of vascular disease for left main coronary artery branch-points. Mean area ratio, the sum of the cross-sectional area of the branches divided by the area of parent vessel, decreased with greater arteriographic disease. Area ratio varies with changes in the relative calibers of branch vessels. Fifty-seven branch-angles were determined by graphic analysis of postmortem biplane coronary arteriograms. No relationship could be found between branch-angle and vessel caliber. The included angle between branches varied from 32 degrees to 124 degrees without respect to relative or absolute vessel calibers. The results of these postmortem measurements on human coronary arteriogram suggest that coronary artery caliber may adjust to minimize energy loss at the branch-point but that branch-angle is determined by other factors. Restudy of arteriograms suggests that branch-angle may be determined by branch vessel destination."} {"id": "PMID:1269109", "title": "The role of angiotensins in aldosterone production.", "content": "The hypothesis that the COOH-terminal heptapeptide mediates the aldosterone-stimulating activity of angiotensin II was evaluated by comparing the relative effects on aldosterone production of angiotensin II and the heptapeptide to angiotensin analogues that are poorly metabolized to the heptapeptide and to a nonapeptide, des-Asp-1-angiotensin I, that is directly converted to the heptapeptide. In in vivo studies utilizing the adrenocorticotropic hormone-suppressed bilaterally nephrectomized dog, angiotensin II and the heptapeptide produced statistically significant increases in both aldosterone and cortisol secretory rates (P less than 0.001 for both relations). Sar-1-angiotensin II stimulated the production of both steroids to the same extent, but had much longer duration of action. [Poly(oAc)Seryl]angiotensin II was a weak agonist, having only about 30% of the steroidogenic potency of either angiotensin II or the heptapeptide. In equimolar concentrations des-Asp-1-angiotensin I had about one-half of the aldosterone-stimulating activity of the hepatpeptide. In in vitro studies, employing the trypsin-dispersed cat adrenal zona glomerulosa cells, the steroidogenic potency of angiotensin II and the heptapeptide was identical to maximal aldosterone production of 10(-8) M peptide concentration. By contrast, the response to Sar-1-angiotensin II was approximately a 10-fold increase in relative potency, while the response to [poly(oAc)Seryl]angiotensin II demonstrated a 10-fold decrease. These findings suggest that, although the heptapeptide may play an important role in the regulation of aldosterone production, the possibility remains open that angiotensin II could stimulate aldosterone biosynthesis without prior conversion to the heptapeptide.", "contents": "The role of angiotensins in aldosterone production. The hypothesis that the COOH-terminal heptapeptide mediates the aldosterone-stimulating activity of angiotensin II was evaluated by comparing the relative effects on aldosterone production of angiotensin II and the heptapeptide to angiotensin analogues that are poorly metabolized to the heptapeptide and to a nonapeptide, des-Asp-1-angiotensin I, that is directly converted to the heptapeptide. In in vivo studies utilizing the adrenocorticotropic hormone-suppressed bilaterally nephrectomized dog, angiotensin II and the heptapeptide produced statistically significant increases in both aldosterone and cortisol secretory rates (P less than 0.001 for both relations). Sar-1-angiotensin II stimulated the production of both steroids to the same extent, but had much longer duration of action. [Poly(oAc)Seryl]angiotensin II was a weak agonist, having only about 30% of the steroidogenic potency of either angiotensin II or the heptapeptide. In equimolar concentrations des-Asp-1-angiotensin I had about one-half of the aldosterone-stimulating activity of the hepatpeptide. In in vitro studies, employing the trypsin-dispersed cat adrenal zona glomerulosa cells, the steroidogenic potency of angiotensin II and the heptapeptide was identical to maximal aldosterone production of 10(-8) M peptide concentration. By contrast, the response to Sar-1-angiotensin II was approximately a 10-fold increase in relative potency, while the response to [poly(oAc)Seryl]angiotensin II demonstrated a 10-fold decrease. These findings suggest that, although the heptapeptide may play an important role in the regulation of aldosterone production, the possibility remains open that angiotensin II could stimulate aldosterone biosynthesis without prior conversion to the heptapeptide."} {"id": "PMID:1269110", "title": "Angiotensin II and angiotensin III in rat blood.", "content": "Angiotensin II and its metabolites, [des-Asp-1]-angiotensin II (angiotensin III), [des-(Asp-1,Arg-2)]angiotensin II, and [des-(Asp-1,Arg-2,val-3)]angiotensin II, were measured in arterial and venous plasma from normal rats. Paper chromatography was used to separate the peptides which were measured with a radioimmunoassay method using an angiotensin II antiserum which had a 100% cross-reaction with each of these metabolites. A mean of 33% of the immunoreactive material in arterial plasma was angiotensin II, 58% angiotensin III, and 9% [des-(Asp-1,Arg-2)]angiotensin II/[des-(Asp-1,Arg-2,Val-3)]angiotensin II. A similar distribution was found in venous plasma. This and other evidence indicates that angiotensin-induced aldosterone secretion in the rat, unlike that in other mammalian species so far studied, may be mediated by angiotensin III.", "contents": "Angiotensin II and angiotensin III in rat blood. Angiotensin II and its metabolites, [des-Asp-1]-angiotensin II (angiotensin III), [des-(Asp-1,Arg-2)]angiotensin II, and [des-(Asp-1,Arg-2,val-3)]angiotensin II, were measured in arterial and venous plasma from normal rats. Paper chromatography was used to separate the peptides which were measured with a radioimmunoassay method using an angiotensin II antiserum which had a 100% cross-reaction with each of these metabolites. A mean of 33% of the immunoreactive material in arterial plasma was angiotensin II, 58% angiotensin III, and 9% [des-(Asp-1,Arg-2)]angiotensin II/[des-(Asp-1,Arg-2,Val-3)]angiotensin II. A similar distribution was found in venous plasma. This and other evidence indicates that angiotensin-induced aldosterone secretion in the rat, unlike that in other mammalian species so far studied, may be mediated by angiotensin III."} {"id": "PMID:1269111", "title": "Interactions between sino-aortic reflexes and cardiovascular effects of sleep and emotional behavior in the cat.", "content": "The role of sino-aortic reflexes in the control of circulation during normal behavior was investigated by comparing cardiovascular reactions during various but reproducible types of behavior before and after bilateral sino-aortic deafferentation. Chronic deafferentation caused little change in baseline blood pressure, but a subtler, important role of sino-aortic reflexes was revealed by examining the integrated cardiovascular responses to behavioral stimuli. During desynchronized sleep, the buffering action of sino-aortic reflexes prevented a marked and diffuse vasodilation, with an action that was particularly evident on muscle blood vessels. During emotional behavior, especially when emotion was accompanied by movement, sino-aortic reflexes opposed the consequences of muscle vasodilation by inducing tachycardia and vasoconstriction in the viscera and in noncontracting muscles. A reciprocal type of interaction between behavior and sino-aortic reflexes was shown by testing the amplitude of the carotid occlusion response before and during desynchronized sleep; the latter condition was consistently associated with decreased effectiveness of the reflex response. The possibility is considered that this might indicate central suppression of the carotid sinus reflex during desynchronized sleep and that a similar inhibitory interference might occur during emotional behavior. Alternatively, reduction of the reflex response might result from a shift of the stimulus-response curve on either side of its steep portion.", "contents": "Interactions between sino-aortic reflexes and cardiovascular effects of sleep and emotional behavior in the cat. The role of sino-aortic reflexes in the control of circulation during normal behavior was investigated by comparing cardiovascular reactions during various but reproducible types of behavior before and after bilateral sino-aortic deafferentation. Chronic deafferentation caused little change in baseline blood pressure, but a subtler, important role of sino-aortic reflexes was revealed by examining the integrated cardiovascular responses to behavioral stimuli. During desynchronized sleep, the buffering action of sino-aortic reflexes prevented a marked and diffuse vasodilation, with an action that was particularly evident on muscle blood vessels. During emotional behavior, especially when emotion was accompanied by movement, sino-aortic reflexes opposed the consequences of muscle vasodilation by inducing tachycardia and vasoconstriction in the viscera and in noncontracting muscles. A reciprocal type of interaction between behavior and sino-aortic reflexes was shown by testing the amplitude of the carotid occlusion response before and during desynchronized sleep; the latter condition was consistently associated with decreased effectiveness of the reflex response. The possibility is considered that this might indicate central suppression of the carotid sinus reflex during desynchronized sleep and that a similar inhibitory interference might occur during emotional behavior. Alternatively, reduction of the reflex response might result from a shift of the stimulus-response curve on either side of its steep portion."} {"id": "PMID:1269112", "title": "Hyperplasia of vascular smooth muscle in experimental hypertension in the rabbit.", "content": "Evidence for smooth muscle cell hyperplasia was sought in elastic and muscular vessels of rabbits 2 weeks after hypertension had been induced by partial constriction of the abdominal aorta above both kidneys. In those arteries taken from the circulation proximal to the constriction, specifically the common carotid artery and the aorta, vessel length, wall thickness, weight, and deoxyribonucleic acid content were increased in proportion to the rise in arterial pressure. There was no change in the extracellular space of muscular arteries as measured by [14C]inulin. [3H]Thymidine uptake measured in a gastric artery increased in proportion to the rise in arterial pressure. As demonstrated by light microscope autoradiography, [3H]thymidine was incorporated into cells in all layers of the artery wall but predominantly into the smooth muscle cells. There was no change in the size of arteries below the ligature where the arterial pressure was within normal limits. The data demonstrated that the increase in vessel wall dimensions in this animal model of hypertension is due in part, during the acute phase, to an increase in the number of cells, particularly vascular smooth muscle cells.", "contents": "Hyperplasia of vascular smooth muscle in experimental hypertension in the rabbit. Evidence for smooth muscle cell hyperplasia was sought in elastic and muscular vessels of rabbits 2 weeks after hypertension had been induced by partial constriction of the abdominal aorta above both kidneys. In those arteries taken from the circulation proximal to the constriction, specifically the common carotid artery and the aorta, vessel length, wall thickness, weight, and deoxyribonucleic acid content were increased in proportion to the rise in arterial pressure. There was no change in the extracellular space of muscular arteries as measured by [14C]inulin. [3H]Thymidine uptake measured in a gastric artery increased in proportion to the rise in arterial pressure. As demonstrated by light microscope autoradiography, [3H]thymidine was incorporated into cells in all layers of the artery wall but predominantly into the smooth muscle cells. There was no change in the size of arteries below the ligature where the arterial pressure was within normal limits. The data demonstrated that the increase in vessel wall dimensions in this animal model of hypertension is due in part, during the acute phase, to an increase in the number of cells, particularly vascular smooth muscle cells."} {"id": "PMID:1269113", "title": "The natriuretic and hypotensive effects of potassium.", "content": "The chronic effects of potassium loading on sodium balance and related variables were studied in two groups of dogs. The first group was intact except for the presence of indwelling arterial and venous cannulas. On the 1st day, increasing daily potassium intake from a normal level (30 mEq/day) to 200 mEq/day produced a 0.47-mEq increase in plasma potassium with a 56% increase (P greater than 0.01) in sodium excretion in spite of a 58% increase in plasma aldosterone concentration. After 6 days of potassium loading the cumulative negative sodium balance averaged 44 mEq while 22Na space decreased 6.7% (P less than 0.025). In this group arterial pressure did not change measurably. The same experimental protocol was repeated in a second group of dogs that were chronically adrenalectomized and maintained on fixed levels of aldosterone (50 mug/day) and hydrocortisone (1 mg/day). With aldosterone levels held constant the same increase in potassium intake produced a 1st day increase in potassium concentration of 1.20 mEq/liter and 217% (P less than 0.001) increase in sodium excretion. After 5 days of high potassium intake, the cumulative negative sodium balance totaled 84 mEq. Sodium space decreased 7.5% (P less than .005) during the course of the 5-day high potassium intake period. Potassium loading caused a fall in mean arterial pressure in this group; pressure fell from the control level of 110 +/- mm Hg to 87 +/- 4 mm Hg (P less than .001) after 3 days of high intake. By the 5th day of the experiment, pressure stabilized at 96 +/- 3 mm Hg, 13% less than (P less than 0.01) the control level. The results suggest that changes in plasma potassium concentration within physiological limits may have long term effects on sodium balance.", "contents": "The natriuretic and hypotensive effects of potassium. The chronic effects of potassium loading on sodium balance and related variables were studied in two groups of dogs. The first group was intact except for the presence of indwelling arterial and venous cannulas. On the 1st day, increasing daily potassium intake from a normal level (30 mEq/day) to 200 mEq/day produced a 0.47-mEq increase in plasma potassium with a 56% increase (P greater than 0.01) in sodium excretion in spite of a 58% increase in plasma aldosterone concentration. After 6 days of potassium loading the cumulative negative sodium balance averaged 44 mEq while 22Na space decreased 6.7% (P less than 0.025). In this group arterial pressure did not change measurably. The same experimental protocol was repeated in a second group of dogs that were chronically adrenalectomized and maintained on fixed levels of aldosterone (50 mug/day) and hydrocortisone (1 mg/day). With aldosterone levels held constant the same increase in potassium intake produced a 1st day increase in potassium concentration of 1.20 mEq/liter and 217% (P less than 0.001) increase in sodium excretion. After 5 days of high potassium intake, the cumulative negative sodium balance totaled 84 mEq. Sodium space decreased 7.5% (P less than .005) during the course of the 5-day high potassium intake period. Potassium loading caused a fall in mean arterial pressure in this group; pressure fell from the control level of 110 +/- mm Hg to 87 +/- 4 mm Hg (P less than .001) after 3 days of high intake. By the 5th day of the experiment, pressure stabilized at 96 +/- 3 mm Hg, 13% less than (P less than 0.01) the control level. The results suggest that changes in plasma potassium concentration within physiological limits may have long term effects on sodium balance."} {"id": "PMID:1269114", "title": "Studies on membrane-bound renin in the mouse and rat.", "content": "Membrane-bound renin was isolated from the submaxillary gland and kidney of the white Swiss Webster mouse and from the kidney of the rat. Administration of the male sex hormone testosterone or an anabolic steroid, such as nandrolone phenpropionate (Durabolin), induces renin activity in microsomal fraction of the submaxillary gland of the young female mouse. Actinomycin D blocks this induction partially. Renin that sedimented with the microsomal fraction was isolated from the homogenized kidney of the mouse by density gradient centrifugation. Microsomal renin was also isolated from rat kidney disrupted by the N2 cavitation technique. The enzyme in the microsomal fraction that had been washed extensively was only partially active, but freezing and thawing or Triton X-100 activated microsomal renin. The same microsomal fraction contained active kallikrein. In pilot studies a plasma membrane-enriched fraction was isolated from the microsomal fraction of the homogenized rat kidney cortex that had both renin and kallikrein activity.", "contents": "Studies on membrane-bound renin in the mouse and rat. Membrane-bound renin was isolated from the submaxillary gland and kidney of the white Swiss Webster mouse and from the kidney of the rat. Administration of the male sex hormone testosterone or an anabolic steroid, such as nandrolone phenpropionate (Durabolin), induces renin activity in microsomal fraction of the submaxillary gland of the young female mouse. Actinomycin D blocks this induction partially. Renin that sedimented with the microsomal fraction was isolated from the homogenized kidney of the mouse by density gradient centrifugation. Microsomal renin was also isolated from rat kidney disrupted by the N2 cavitation technique. The enzyme in the microsomal fraction that had been washed extensively was only partially active, but freezing and thawing or Triton X-100 activated microsomal renin. The same microsomal fraction contained active kallikrein. In pilot studies a plasma membrane-enriched fraction was isolated from the microsomal fraction of the homogenized rat kidney cortex that had both renin and kallikrein activity."} {"id": "PMID:1269115", "title": "Mitral atresia with normal aortic valve: a study of eighteen cases and a review of the literature.", "content": "Eighteen cases of mitral atresia with normal aortic valve plus 68 cases from the literature are analyzed. A new classification based on anatomical findings is proposed. Pulmonary stenosis or atresia is frequent in the type with transposition of the great arteries. The rare instances of normal or large left ventricle are due to a large ventricular septal defect, or to straddling or displaced tricuspid valve. The clinical, radiologic and electrocardiographic findings have been summarized and correlated with the different physiopathological situations. In our catheterized cases an oxygen saturation step-up was found in the right atrium together with left atrial hypertension. In seven cases mitral atresia was demonstrated by selective left atrial contrast injection. The average age at death was six months. Among the cases surviving one year or more, the association of atrial septal defects or pulmonary stenosis was frequent. Enlargement of the interatrial communication, accompanied by other palliative measures, is the only available surgical procedure.", "contents": "Mitral atresia with normal aortic valve: a study of eighteen cases and a review of the literature. Eighteen cases of mitral atresia with normal aortic valve plus 68 cases from the literature are analyzed. A new classification based on anatomical findings is proposed. Pulmonary stenosis or atresia is frequent in the type with transposition of the great arteries. The rare instances of normal or large left ventricle are due to a large ventricular septal defect, or to straddling or displaced tricuspid valve. The clinical, radiologic and electrocardiographic findings have been summarized and correlated with the different physiopathological situations. In our catheterized cases an oxygen saturation step-up was found in the right atrium together with left atrial hypertension. In seven cases mitral atresia was demonstrated by selective left atrial contrast injection. The average age at death was six months. Among the cases surviving one year or more, the association of atrial septal defects or pulmonary stenosis was frequent. Enlargement of the interatrial communication, accompanied by other palliative measures, is the only available surgical procedure."} {"id": "PMID:1269116", "title": "Anomalies of the aortic arch and ventricular septal defects.", "content": "This investigation presents additional evidence for the hemodynamic influence of intracardiac anomalies on the development of the aortic arch, based on measurements of different parts of the great vessels. Criteria are given to define the normal aortic arch and the different anomalies of the aortic arch, such as interruption, atresia, tubular hypoplasia, hypoplasia, abnormal long segment and juxtaductal coarctation. Two types of of malignment venentricular septal defects are described to illustrate how prenatal intracardiac flow disturbances can account for various aortic arch patterns. An explanation is proposed as to how reduced blood flow through the embryonic preductal aorta may contribute to the pathogenesis of all dimensional anomalies of the aortic arch.", "contents": "Anomalies of the aortic arch and ventricular septal defects. This investigation presents additional evidence for the hemodynamic influence of intracardiac anomalies on the development of the aortic arch, based on measurements of different parts of the great vessels. Criteria are given to define the normal aortic arch and the different anomalies of the aortic arch, such as interruption, atresia, tubular hypoplasia, hypoplasia, abnormal long segment and juxtaductal coarctation. Two types of of malignment venentricular septal defects are described to illustrate how prenatal intracardiac flow disturbances can account for various aortic arch patterns. An explanation is proposed as to how reduced blood flow through the embryonic preductal aorta may contribute to the pathogenesis of all dimensional anomalies of the aortic arch."} {"id": "PMID:1269117", "title": "XVIII. Persistent fetal dispersion of the atrioventricular node and His bundle within the central fibrous body.", "content": "In the hearts of two victims of sudden unexpected death (one age 20 years and the other 11 years) there was abnormally delayed persistence of the pattern of fetal dispersion of the A-V (atrioventricular) node and His bundle within the central fibrous body. This pattern is characterized by a splayed or excessively fragmented histological appearance of these structures viewed in cross-section. Some of the fronds of A-V nodal tissue formed loops connecting one portion of the node to another. Other fragments of nodal tissue appeared isolated within the central fibrous body, occasionally connecting directly to the crest of the interventricular septum. A number of the A-V nodal fragments were undergoing resorptive degeneration. Directly adjacent to the A-V node of the 11-year-old subject there was an island of cartilage within the central fibrous body. Since these anatomically separated fragments of A-V nodal tissue were so numerous and varied widely in size and thickness, in length, in histological organization, and in their apparent state of preservation probably extant during life, it is suggested that they form potential routes for abnormal conduction or impulse formation within the A-V junctional region and that some of these electrophysiological disturbances might be quickly lethal.", "contents": "XVIII. Persistent fetal dispersion of the atrioventricular node and His bundle within the central fibrous body. In the hearts of two victims of sudden unexpected death (one age 20 years and the other 11 years) there was abnormally delayed persistence of the pattern of fetal dispersion of the A-V (atrioventricular) node and His bundle within the central fibrous body. This pattern is characterized by a splayed or excessively fragmented histological appearance of these structures viewed in cross-section. Some of the fronds of A-V nodal tissue formed loops connecting one portion of the node to another. Other fragments of nodal tissue appeared isolated within the central fibrous body, occasionally connecting directly to the crest of the interventricular septum. A number of the A-V nodal fragments were undergoing resorptive degeneration. Directly adjacent to the A-V node of the 11-year-old subject there was an island of cartilage within the central fibrous body. Since these anatomically separated fragments of A-V nodal tissue were so numerous and varied widely in size and thickness, in length, in histological organization, and in their apparent state of preservation probably extant during life, it is suggested that they form potential routes for abnormal conduction or impulse formation within the A-V junctional region and that some of these electrophysiological disturbances might be quickly lethal."} {"id": "PMID:1269125", "title": "Left axis deviation: a spectrum of intraventricular conduction block.", "content": "The effects of left axis shift (greater than -30 degrees) on intraventricular conduction time (IVCT) were studied in 63 subjects in whom electrocardiograms before and after appearance of the left axis shift were available. Subjects with electrocardiographic evidence of left or right ventricular hypertrophy, left or right bundle branch block, myocardial infarction, pre-excitation and those receiving antiarrthymic drugs were excluded. The IVCT increased by an average of 25 msec when the QRS axis shifted to -30 degrees or beyond. When the individual AQRS was related to the IVCT a linear correlation (r = -0.8) was observed. It appears that a continuum relation between the AQRS and the IVCT exists throughout the counterclockwise range of +90 degrees to -90 degees. In all leftward shifts in AQRS from from +90 degrees there is a prolongation in IVCT. Our observations indicate that all leftward shifts in AQRS, including the extreme left axis shift (left anterior hemiblock), represent a spectrum of intraventricular conduction block.", "contents": "Left axis deviation: a spectrum of intraventricular conduction block. The effects of left axis shift (greater than -30 degrees) on intraventricular conduction time (IVCT) were studied in 63 subjects in whom electrocardiograms before and after appearance of the left axis shift were available. Subjects with electrocardiographic evidence of left or right ventricular hypertrophy, left or right bundle branch block, myocardial infarction, pre-excitation and those receiving antiarrthymic drugs were excluded. The IVCT increased by an average of 25 msec when the QRS axis shifted to -30 degrees or beyond. When the individual AQRS was related to the IVCT a linear correlation (r = -0.8) was observed. It appears that a continuum relation between the AQRS and the IVCT exists throughout the counterclockwise range of +90 degrees to -90 degees. In all leftward shifts in AQRS from from +90 degrees there is a prolongation in IVCT. Our observations indicate that all leftward shifts in AQRS, including the extreme left axis shift (left anterior hemiblock), represent a spectrum of intraventricular conduction block."} {"id": "PMID:1269126", "title": "The effect of premature atrial depolarization on sinus node automaticity in man.", "content": "Sino-atrial conduction time (SACT) may be calculated from the difference between the length of the return cycle and the spontaneous cycle, using programmed premature atrial stimulation during spontaneous sinus rhythm. This approach to sinoatrial conduction assumes that sinus node automaticity is not changed by premature depolarization. In order to validate this assumption, we compared the length of the post-return cycles to the spontaneous cycle length in 71 patients. Patients were grouped according to clinical diagnosis and the value of calculated SACT. At long coupling intervals at which no reset of the sinus node occurred there was only a small prolongation of the post-return cycles (less than 8.4 msec, on an average) compared to the spontaneous cycle length. This suggests no or only an insignificant effect of premature depolarization on the sinus node. However, during test stimuli leading to reset of the sinus node, the post-return cycles were significantly prolonged between 20 to 30 msec, on an average. The response of the individual cases sometimes varied to a great extent. In patients who demonstrated a progressive linear prolongation of the return cycles at decremental shortening of the test interval, there was no significant prolongation of the post-return cycles versus the spontaneous cycle length. We conclude that 1) premature depolarization of the sinus node may have a depressant effect on sinus node automaticity, which, if present, is usually small; 2) calculation of SACT using the extrastimulus technique may overestimate true SACT.", "contents": "The effect of premature atrial depolarization on sinus node automaticity in man. Sino-atrial conduction time (SACT) may be calculated from the difference between the length of the return cycle and the spontaneous cycle, using programmed premature atrial stimulation during spontaneous sinus rhythm. This approach to sinoatrial conduction assumes that sinus node automaticity is not changed by premature depolarization. In order to validate this assumption, we compared the length of the post-return cycles to the spontaneous cycle length in 71 patients. Patients were grouped according to clinical diagnosis and the value of calculated SACT. At long coupling intervals at which no reset of the sinus node occurred there was only a small prolongation of the post-return cycles (less than 8.4 msec, on an average) compared to the spontaneous cycle length. This suggests no or only an insignificant effect of premature depolarization on the sinus node. However, during test stimuli leading to reset of the sinus node, the post-return cycles were significantly prolonged between 20 to 30 msec, on an average. The response of the individual cases sometimes varied to a great extent. In patients who demonstrated a progressive linear prolongation of the return cycles at decremental shortening of the test interval, there was no significant prolongation of the post-return cycles versus the spontaneous cycle length. We conclude that 1) premature depolarization of the sinus node may have a depressant effect on sinus node automaticity, which, if present, is usually small; 2) calculation of SACT using the extrastimulus technique may overestimate true SACT."} {"id": "PMID:1269127", "title": "The vectorcardiogram in right bundle branch block: correlation with cardiac failure and pulmonary disease.", "content": "Frank vectorcardiograms (VCG) and clinical records of 243 patients with right bundle branch block (RBBB) were compared. The patients were classified into three categories on the basis of VCG criteria. The first category included 100 patients with a normal frontal axis, and the second category included 44 patients with concomitant left anterior hemiblock. The third category consisted of 99 patients with RBBB and myocardial infarction. The VCGs were classified into three types accoriding to the QRS configuration in the transverse plane. In type I the initial forces were anterior and counterclockwise and the afferent limb crossed the midline posterior to E point; in type II the initial forces were anterior and counterclockwise and the afferent limb crossed the midline posterior to E point; in type II the initial forces were anterior and counterclockwise and the afferent limb crossed the midline anterior to or through E point; and in type III the entire transverse loop was clockwise and anterior to E point. The patients were further classified according to the presence or absence of cardic failure or severe pulmonary disease. In patients with RBBB and a normal axis, cardiac failure or severe pulmonary disease was found in five of 49 patients wtih type I, 17 of 31 with type II, and 18 of 20 with type III pattern. In patients with RBBB and left anterior hemiblock, significant disease was found in one of 17 with type I, five of 16 with type II, and eight of 11 with type III pattern. These data show that, in patients with RBBB, the position of the afferent limb in the transverse plane can be used to predict cardiac failure or severe pulmonary disease.", "contents": "The vectorcardiogram in right bundle branch block: correlation with cardiac failure and pulmonary disease. Frank vectorcardiograms (VCG) and clinical records of 243 patients with right bundle branch block (RBBB) were compared. The patients were classified into three categories on the basis of VCG criteria. The first category included 100 patients with a normal frontal axis, and the second category included 44 patients with concomitant left anterior hemiblock. The third category consisted of 99 patients with RBBB and myocardial infarction. The VCGs were classified into three types accoriding to the QRS configuration in the transverse plane. In type I the initial forces were anterior and counterclockwise and the afferent limb crossed the midline posterior to E point; in type II the initial forces were anterior and counterclockwise and the afferent limb crossed the midline posterior to E point; in type II the initial forces were anterior and counterclockwise and the afferent limb crossed the midline anterior to or through E point; and in type III the entire transverse loop was clockwise and anterior to E point. The patients were further classified according to the presence or absence of cardic failure or severe pulmonary disease. In patients with RBBB and a normal axis, cardiac failure or severe pulmonary disease was found in five of 49 patients wtih type I, 17 of 31 with type II, and 18 of 20 with type III pattern. In patients with RBBB and left anterior hemiblock, significant disease was found in one of 17 with type I, five of 16 with type II, and eight of 11 with type III pattern. These data show that, in patients with RBBB, the position of the afferent limb in the transverse plane can be used to predict cardiac failure or severe pulmonary disease."} {"id": "PMID:1269128", "title": "The conducting tissues in primitive ventricular hearts without an outlet chamber.", "content": "We have studied the disposition of the cardiac conducting tissues in four hearts from situs solitus individuals possessing primitive ventricles without outlet chambers. These hearts correspond to the type of univentricular heart defined as common ventricle by Lev. All the hearts studied possessed normally positioned great arteries. Two groups, each consisting of two hearts, could be distinguished. The first type possessed a small posterior ridge which divided the posterior portion of the primitive ventricle into right and left ventricular sinuses. The papillary muscles to the atrioventricular valves were separate structures and arose on each side of this posterior ridge. The conducting tissues in these hearts arose from an atrioventricular node situated in the atrial septum but deviated posteriorly. The atrioventricular bundle pierced the fibrous annulus posteriorly and descended on the posterior ridge, lying to its left side. A bifurcation was not identified, and bundle branches were not present. The other two hearts had no posterior ridge. A common posterior papillary muscle supported both atrioventricular valves, and in one a marked anterior muscle bar produced obstruction of the pulmonary outflow tract. The connecting atrioventricular node was situated laterally in the right atrioventricular valve orifice, and the atrioventricular bundle descended into the right parietal wall of the primitive ventricle. A bifurcation and bundle branches were not observed. The disposition of conducting tissue in these hearts differs from that found in \"primitive ventricle with outlet chamber\" in that the connecting atrioventricular node and bundle are situated anteriorly and are intimately related to the transposed pulmonary artery outflow tract in the latter anomaly. The surgical significance of these findings is emphasized.", "contents": "The conducting tissues in primitive ventricular hearts without an outlet chamber. We have studied the disposition of the cardiac conducting tissues in four hearts from situs solitus individuals possessing primitive ventricles without outlet chambers. These hearts correspond to the type of univentricular heart defined as common ventricle by Lev. All the hearts studied possessed normally positioned great arteries. Two groups, each consisting of two hearts, could be distinguished. The first type possessed a small posterior ridge which divided the posterior portion of the primitive ventricle into right and left ventricular sinuses. The papillary muscles to the atrioventricular valves were separate structures and arose on each side of this posterior ridge. The conducting tissues in these hearts arose from an atrioventricular node situated in the atrial septum but deviated posteriorly. The atrioventricular bundle pierced the fibrous annulus posteriorly and descended on the posterior ridge, lying to its left side. A bifurcation was not identified, and bundle branches were not present. The other two hearts had no posterior ridge. A common posterior papillary muscle supported both atrioventricular valves, and in one a marked anterior muscle bar produced obstruction of the pulmonary outflow tract. The connecting atrioventricular node was situated laterally in the right atrioventricular valve orifice, and the atrioventricular bundle descended into the right parietal wall of the primitive ventricle. A bifurcation and bundle branches were not observed. The disposition of conducting tissue in these hearts differs from that found in \"primitive ventricle with outlet chamber\" in that the connecting atrioventricular node and bundle are situated anteriorly and are intimately related to the transposed pulmonary artery outflow tract in the latter anomaly. The surgical significance of these findings is emphasized."} {"id": "PMID:1269129", "title": "Review of the pocket-electrocardiograph (PECG) in a large general medical clinic.", "content": "Two hundred and twenty patients were selected for testing with the patient-activated Pocket Electrocardiography (PECG) because angina pectoris and similar diagnoses could not be excluded. They were selected during a 30-month period from the population of approximately 12,000 new patients visiting a general medical clinic at Nippon Medical School Hospital. The test confirmed the preliminary diagnosis in 79.1%; 9.6% were not confirmed and 11.3% did not have an attack during the PECG examination. The PECG examination is useful in the differential diagnosis of angina pectoris, cardiac neurosis, phantom arrhythmia, and arrhythmia when the routine ECG examinations are essentially negative.", "contents": "Review of the pocket-electrocardiograph (PECG) in a large general medical clinic. Two hundred and twenty patients were selected for testing with the patient-activated Pocket Electrocardiography (PECG) because angina pectoris and similar diagnoses could not be excluded. They were selected during a 30-month period from the population of approximately 12,000 new patients visiting a general medical clinic at Nippon Medical School Hospital. The test confirmed the preliminary diagnosis in 79.1%; 9.6% were not confirmed and 11.3% did not have an attack during the PECG examination. The PECG examination is useful in the differential diagnosis of angina pectoris, cardiac neurosis, phantom arrhythmia, and arrhythmia when the routine ECG examinations are essentially negative."} {"id": "PMID:1269130", "title": "The influence of left ventricular stroke volume on aortic root motion: an echocardiographic study.", "content": "Aortic root motion was studied in 24 normal volunteers at rest and during the Valsalva maneuver, isometric exercise, and amyl nitrite inhalation. In addition root motion was correlated with the stroke volumes determined at cardiac catheterization in 24 patients. The root has distinct systolic movement, the amplitude and duration of which were easily measured both at rest and during the interventions. At rest,the mean (+/-1 SE) systolic amplitude of the anterior aortic wall was 11.2 +/- 0.5 mm and that of the posterior wall 9.5 +/- 0.3 mm. During the strain phase of the Valsalva maneuver anterior wall amplitude fell to 8.2 +/- 0.4 mm and the posterior wall to 7.3 +/- 0.5 mm (P less than 0.001). With release, anterior wall amplitude rebounded to 12.5 +/- 0.8 mm and the posterior wall to 10.8 +/- o.5 mm, values greater than control (P less than 0.01). With isometric exercise there was no change in amplitude compared to rest; however, amyl nitrite caused an increase in the anterior wall to 13.5 +/-0.8 mm and posterior wall to 11.9 +/-0.6 mm (P less than 0.01). In the patient group the amplitude of posterior wall motion correlated weakly with cardiac index (r = 0.63) and stronger with stroke index (r = 0.78). This study quantifies the echocardiographic pattern of normal aortic root motion. The findings indicate that the aortic root motion is an index of stroke volume; they further suggest that root motion is acutely sensitive to variations in stroke volume since its amplitude changed in accord with the documented effects of the employed maneuvers on stroke volume.", "contents": "The influence of left ventricular stroke volume on aortic root motion: an echocardiographic study. Aortic root motion was studied in 24 normal volunteers at rest and during the Valsalva maneuver, isometric exercise, and amyl nitrite inhalation. In addition root motion was correlated with the stroke volumes determined at cardiac catheterization in 24 patients. The root has distinct systolic movement, the amplitude and duration of which were easily measured both at rest and during the interventions. At rest,the mean (+/-1 SE) systolic amplitude of the anterior aortic wall was 11.2 +/- 0.5 mm and that of the posterior wall 9.5 +/- 0.3 mm. During the strain phase of the Valsalva maneuver anterior wall amplitude fell to 8.2 +/- 0.4 mm and the posterior wall to 7.3 +/- 0.5 mm (P less than 0.001). With release, anterior wall amplitude rebounded to 12.5 +/- 0.8 mm and the posterior wall to 10.8 +/- o.5 mm, values greater than control (P less than 0.01). With isometric exercise there was no change in amplitude compared to rest; however, amyl nitrite caused an increase in the anterior wall to 13.5 +/-0.8 mm and posterior wall to 11.9 +/-0.6 mm (P less than 0.01). In the patient group the amplitude of posterior wall motion correlated weakly with cardiac index (r = 0.63) and stronger with stroke index (r = 0.78). This study quantifies the echocardiographic pattern of normal aortic root motion. The findings indicate that the aortic root motion is an index of stroke volume; they further suggest that root motion is acutely sensitive to variations in stroke volume since its amplitude changed in accord with the documented effects of the employed maneuvers on stroke volume."} {"id": "PMID:1269131", "title": "Quantitative ultrasonographic studies of lower extremity flow velocities in health and disease.", "content": "Quantitative Doppler ultrasonographic flow velocity determinations are reported from 39 normal control subjects and 80 patients with angiographically documented peripheral arterial disease, in whom femoral, posterior tibial and dorsalis pedis arteries were studied. The mean control values of the most useful parameters were: femoral artery: peak forward velocity (PFV) cm/sec: 40.7 +/- 10.9, deceleration (Dec.) cm/sec2:250.9 +/- 60.0, peak/mean velocity (P/MV): 4.8 +/- 1.6; posterior tibial artery: PFV: 16.0 +/- 10.0, Dec.: 129.8 +/- 75.7, P/MV: 4.8 +/- 2.5; dorsalis pedis artery: PFV: 168 +/- 5.7, Dec.: 137.9 +/- 54.5, P/MV: 6.0 +/- 4.1. The values of these measurements in the patients with arterial occlusive disease were all significantly lower, and also permitted distinguishing those with multilevel disease from those with a single site of occlusion. Quantitative evaluation of the Doppler ultrasonogram permits obtaining detailed functional information on the degree of arterial flow impairment in patients with peripheral arterial occlusive disease.", "contents": "Quantitative ultrasonographic studies of lower extremity flow velocities in health and disease. Quantitative Doppler ultrasonographic flow velocity determinations are reported from 39 normal control subjects and 80 patients with angiographically documented peripheral arterial disease, in whom femoral, posterior tibial and dorsalis pedis arteries were studied. The mean control values of the most useful parameters were: femoral artery: peak forward velocity (PFV) cm/sec: 40.7 +/- 10.9, deceleration (Dec.) cm/sec2:250.9 +/- 60.0, peak/mean velocity (P/MV): 4.8 +/- 1.6; posterior tibial artery: PFV: 16.0 +/- 10.0, Dec.: 129.8 +/- 75.7, P/MV: 4.8 +/- 2.5; dorsalis pedis artery: PFV: 168 +/- 5.7, Dec.: 137.9 +/- 54.5, P/MV: 6.0 +/- 4.1. The values of these measurements in the patients with arterial occlusive disease were all significantly lower, and also permitted distinguishing those with multilevel disease from those with a single site of occlusion. Quantitative evaluation of the Doppler ultrasonogram permits obtaining detailed functional information on the degree of arterial flow impairment in patients with peripheral arterial occlusive disease."} {"id": "PMID:1269132", "title": "Myocardial ischemia due to infrarenal aortic cross-clamping during aortic surgery in patients with severe coronary artery disease.", "content": "Hemodynamic measurements were performed and ECG recorded before and shortly after infrarenal aortic cross-clamping during operation for abdominal aortic aneurysm in five patients without evidence of heart disease (group I) and in ten patients with severe coronary artery disease (group II). All patients sustained an increase in systemic arterial pressure. Group I demonstrated a decrease in pulmonary artery, pulmonary capillary wedge (PCW), and central venous pressures when the aorta was clamped, whereas group II demonstrated an increase. The difference in response of the groups is significant (P less than 0.05). All three patients who responded to cross-clamping with increases of 7 mm Hg or greater in PCW demonstrated myocardial ischemia during cross-clamping. None of the values measured prior to cross-clamping predicted with certainty the response to cross-clamping. Sodium nitroprusside reversed the elevation of left ventricular filling pressure in all three patients, and in two patients, relieved evidence of myocardial ischemia concurrently. In the third patient, ventricular irritability was abolished by lidocaine and did not recur. We conclude that infrarenal aortic cross-clamping may cause myocardial ischemia in patients with severe coronary artery disease. This ischemia may be predicted by a rise in PCW at the time of cross-clamping, and vasodilator therapy is indicated in such patients.", "contents": "Myocardial ischemia due to infrarenal aortic cross-clamping during aortic surgery in patients with severe coronary artery disease. Hemodynamic measurements were performed and ECG recorded before and shortly after infrarenal aortic cross-clamping during operation for abdominal aortic aneurysm in five patients without evidence of heart disease (group I) and in ten patients with severe coronary artery disease (group II). All patients sustained an increase in systemic arterial pressure. Group I demonstrated a decrease in pulmonary artery, pulmonary capillary wedge (PCW), and central venous pressures when the aorta was clamped, whereas group II demonstrated an increase. The difference in response of the groups is significant (P less than 0.05). All three patients who responded to cross-clamping with increases of 7 mm Hg or greater in PCW demonstrated myocardial ischemia during cross-clamping. None of the values measured prior to cross-clamping predicted with certainty the response to cross-clamping. Sodium nitroprusside reversed the elevation of left ventricular filling pressure in all three patients, and in two patients, relieved evidence of myocardial ischemia concurrently. In the third patient, ventricular irritability was abolished by lidocaine and did not recur. We conclude that infrarenal aortic cross-clamping may cause myocardial ischemia in patients with severe coronary artery disease. This ischemia may be predicted by a rise in PCW at the time of cross-clamping, and vasodilator therapy is indicated in such patients."} {"id": "PMID:1269133", "title": "Diagnosis of acute myocardial infarction in a community hospital: significance of CPK-MB determination.", "content": "Twice-daily CPK-MB determinations were performed but not made availabe to the physicians of 179 consecutive patients with precordial pain admitted to a community hospital to evaluate the diagnostic importance of this isoenzyme. Physician decision was based upon history and once-daily ECG and total enzymes (CPK, SGOT, LDH). Following hospital discharge, each patient's clinical record was reviewed to determine the physician diagnostic decision. The patients were subdivided into three groups. The first group consisted of 46 patients with diagnostic QRS changes and elevated total enzymes. All 46 had physician diagnosis of acute myocardial infarction and CPK-MB was present in 44 (96%). The second group included 55 patients with nondiagnostic QRS but elevated total enzymes. Physician diagnosis was acute myocardial infarction in 28 (51%) but 16 (57%) of these had no CPK-MB. The third group contained 50 patients with nondiagnostic QRS and normal enzyme levels. Six (12%) had physician diagnosis of acute myocardial infarction but none had CPK-MB. Thus, absence of CPK-MB failed to confirm physician diagnosis of acute myocardial infarction when based upon history and total enzymes in the absence of QRS changes in 22 of 34 (65%) patients.", "contents": "Diagnosis of acute myocardial infarction in a community hospital: significance of CPK-MB determination. Twice-daily CPK-MB determinations were performed but not made availabe to the physicians of 179 consecutive patients with precordial pain admitted to a community hospital to evaluate the diagnostic importance of this isoenzyme. Physician decision was based upon history and once-daily ECG and total enzymes (CPK, SGOT, LDH). Following hospital discharge, each patient's clinical record was reviewed to determine the physician diagnostic decision. The patients were subdivided into three groups. The first group consisted of 46 patients with diagnostic QRS changes and elevated total enzymes. All 46 had physician diagnosis of acute myocardial infarction and CPK-MB was present in 44 (96%). The second group included 55 patients with nondiagnostic QRS but elevated total enzymes. Physician diagnosis was acute myocardial infarction in 28 (51%) but 16 (57%) of these had no CPK-MB. The third group contained 50 patients with nondiagnostic QRS and normal enzyme levels. Six (12%) had physician diagnosis of acute myocardial infarction but none had CPK-MB. Thus, absence of CPK-MB failed to confirm physician diagnosis of acute myocardial infarction when based upon history and total enzymes in the absence of QRS changes in 22 of 34 (65%) patients."} {"id": "PMID:1269134", "title": "Experimental myocardial infarction. XIII. Sequential changes in left ventricular pressure-length relationships in the acute phase.", "content": "Diastolic pressure-length relationships of an ischemic region of the canine left ventricle were measured over a six-hour period following left anterior descending coronary artery ligation, and their evolution was compared with the extent of systolic aneurysmal bulging. Normalized ischemic segment length excursion, which after coronary artery ligation may be taken as a measure of systolic aneurysmal bulging, increased during the first hour after ligation but thereafter declined toward control values. Concurrently, reciprocal changes were demonstrated in the slope of the end-diastolic pressure-length curves obtained during transient pressure loading of the left ventricle. These data show that the magnitude of acute systolic aneurysmal bulging followed experimental coronary artery ligation is determined not only by loss of contractile function, but also by changes in passive pressure-length relationships of the myocardium. Moreover, the results indicate that development of akinesis in experimental ischemia, heretofore demonstrated only in the chronic phase of infarction, may begin within hours of the onset of myocardial ischemia.", "contents": "Experimental myocardial infarction. XIII. Sequential changes in left ventricular pressure-length relationships in the acute phase. Diastolic pressure-length relationships of an ischemic region of the canine left ventricle were measured over a six-hour period following left anterior descending coronary artery ligation, and their evolution was compared with the extent of systolic aneurysmal bulging. Normalized ischemic segment length excursion, which after coronary artery ligation may be taken as a measure of systolic aneurysmal bulging, increased during the first hour after ligation but thereafter declined toward control values. Concurrently, reciprocal changes were demonstrated in the slope of the end-diastolic pressure-length curves obtained during transient pressure loading of the left ventricle. These data show that the magnitude of acute systolic aneurysmal bulging followed experimental coronary artery ligation is determined not only by loss of contractile function, but also by changes in passive pressure-length relationships of the myocardium. Moreover, the results indicate that development of akinesis in experimental ischemia, heretofore demonstrated only in the chronic phase of infarction, may begin within hours of the onset of myocardial ischemia."} {"id": "PMID:1269135", "title": "Effects of procainamide on the dispersion of recovery of excitability during coronary occlusion.", "content": "In 14 mongrel dogs, refractory periods were determined in nonischemic and acutely ischemic zones of myocardium during control conditions, 15 minutes after coronary ligation, and 10 and 20 minutes after a procainamide infusion. Following coronary ligation, refractory periods in the nonischemic area remained unchanged (100.8% of control) while in the ischemia area they decreased to 88.6% of control (P less than 0.02) causing a dispersion of refractoriness of 12.2%. After the administration of procainamide, refractory periods lengthened in the nonischemic as well as in the ischemic areas but the changes were such that the temporal dispersion caused by the coronary ligation was reduced from 12.2% to 5.5% (P less than 0.01) after 10 minutes, and to 5.0% (P less than 0.02) after 20 minutes of drug infusion. It is concluded that procainamide exerts different overall effects on the nonischemic and acutely ischemic canine myocardium. It is postulated that this action may play a role in the suppression of re-entrant arrhythmias.", "contents": "Effects of procainamide on the dispersion of recovery of excitability during coronary occlusion. In 14 mongrel dogs, refractory periods were determined in nonischemic and acutely ischemic zones of myocardium during control conditions, 15 minutes after coronary ligation, and 10 and 20 minutes after a procainamide infusion. Following coronary ligation, refractory periods in the nonischemic area remained unchanged (100.8% of control) while in the ischemia area they decreased to 88.6% of control (P less than 0.02) causing a dispersion of refractoriness of 12.2%. After the administration of procainamide, refractory periods lengthened in the nonischemic as well as in the ischemic areas but the changes were such that the temporal dispersion caused by the coronary ligation was reduced from 12.2% to 5.5% (P less than 0.01) after 10 minutes, and to 5.0% (P less than 0.02) after 20 minutes of drug infusion. It is concluded that procainamide exerts different overall effects on the nonischemic and acutely ischemic canine myocardium. It is postulated that this action may play a role in the suppression of re-entrant arrhythmias."} {"id": "PMID:1269136", "title": "Noninvasive detection of intracardiac thrombosis: 131-I fibrinogen cardiac survey.", "content": "Cardiac survey following administration of 131-1 autologous fibrinogen is a noninvasive technique for the detection of intracardiac thrombosis. Fibrinogen is isolated from plasma by a rapid salting-out method with ammonium sulfate and is iodinated with chloramine T. The purity of 131-fibrinogen, expressed as clottable radioactivity, is greater than 90%. Cardiac survey consisting of serial gamma camera imaging or rectilinear scanning after intravenous administration of 131-I fibrinogen was conducted in dogs with freshly induced thromobosis of the left atrial appendage. An accumulation of radioactivity was detectable in the area of the left atrium and confirmed in each of nine dogs sacrificed. Similarly, 20 patients with heart disease predisposing to intracardiac thrombosis were surveyed. Eight of nine patients with positive studies and 11 of 11 with negative studies were confirmed subsequently at surgery or autopsy. Cardiac survey with 131-I fibrinogen is a simple and noninvasive method of detecting intracardiac thrombosis.", "contents": "Noninvasive detection of intracardiac thrombosis: 131-I fibrinogen cardiac survey. Cardiac survey following administration of 131-1 autologous fibrinogen is a noninvasive technique for the detection of intracardiac thrombosis. Fibrinogen is isolated from plasma by a rapid salting-out method with ammonium sulfate and is iodinated with chloramine T. The purity of 131-fibrinogen, expressed as clottable radioactivity, is greater than 90%. Cardiac survey consisting of serial gamma camera imaging or rectilinear scanning after intravenous administration of 131-I fibrinogen was conducted in dogs with freshly induced thromobosis of the left atrial appendage. An accumulation of radioactivity was detectable in the area of the left atrium and confirmed in each of nine dogs sacrificed. Similarly, 20 patients with heart disease predisposing to intracardiac thrombosis were surveyed. Eight of nine patients with positive studies and 11 of 11 with negative studies were confirmed subsequently at surgery or autopsy. Cardiac survey with 131-I fibrinogen is a simple and noninvasive method of detecting intracardiac thrombosis."} {"id": "PMID:1269137", "title": "Scanning electron microscopy of surface irregularities and thrombogenesis of polyurethane and polyethylene coronary catheters.", "content": "Following routine coronary arteriography, surface irregularities and thrombogenesis of the inner and outer wall of six Ducor polyurethane and six RPX polyethylene coronary catheters were studied by scanning electron microscopy. Polyurethane catheters had rough and highly irregular external and internal surfaces. All catheters showed adherent thrombi on their external surface. The internal surface of three catheters showed evidence of thrombosis. Polyethylene differed from polyurethane in several respects. Although the external surface had an irregular and wavelike appearance, the internal surface was smooth and regular. Two polyethylene catheters showed thrombi on their external surface. The internal surface of one catheter showed single platelets in one area. These results confirm recent reports showing that internal and external surface irregularities play a major role in the initiation of thrombosis in and on intravascular catheters. They stress the need for high quality catheter materials with smooth and regular surfaces in the prevention of thromboembolic complications from coronary arteriography.", "contents": "Scanning electron microscopy of surface irregularities and thrombogenesis of polyurethane and polyethylene coronary catheters. Following routine coronary arteriography, surface irregularities and thrombogenesis of the inner and outer wall of six Ducor polyurethane and six RPX polyethylene coronary catheters were studied by scanning electron microscopy. Polyurethane catheters had rough and highly irregular external and internal surfaces. All catheters showed adherent thrombi on their external surface. The internal surface of three catheters showed evidence of thrombosis. Polyethylene differed from polyurethane in several respects. Although the external surface had an irregular and wavelike appearance, the internal surface was smooth and regular. Two polyethylene catheters showed thrombi on their external surface. The internal surface of one catheter showed single platelets in one area. These results confirm recent reports showing that internal and external surface irregularities play a major role in the initiation of thrombosis in and on intravascular catheters. They stress the need for high quality catheter materials with smooth and regular surfaces in the prevention of thromboembolic complications from coronary arteriography."} {"id": "PMID:1269138", "title": "Alterations of right ventricular systolic time intervals by chronic pressure and volume overloading.", "content": "Right ventricular (RV) systolic time intervals and hemodynamic parameters were determined by micromanometric techniques in 13 subjects with normal right ventricles (NRV). These data were compared to those of 16 patients with pulmonary hypertension (PH) or predominant pressure overloading and 13 individuals with uncomplicated secundum atrial septal defects (ASD) or predominant volume overloading. In PH, the QP2 interval tends to remain within the normal range due to reciprocal changes in isovolumic contraction (ICT) and ejection (RVET) times. Elevations of pulmonary artery diastolic pressure are associated with increases in the mean rate of isovolumic pressure rise (MRIPR) (r = 0.84), but the latter change does not fully compensate for the widened ventriculoarterial diastolic pressure difference and ICT becomes prolonged (P less than 0.001). Factors other than stroke index depression which may contribute to the decreased duration of RVET (P less than 0.001) include tricuspid regurgitation and elevation of pulmonary vascular impedance. In ASD, QP2 is significantly prolonged (P less than 0.025) due to a significant increase in RVET (P less than 0.005). In contrast to NRV, a linear correlation of RVET and stroke index was not present, which suggested an alteration of ejection dynamics in this group. Despite a high incidence of complete or incomplete right bundle branch block the interval from QRS onset to rapid RV pressure upstroke was not prolonged. This is most probably the result of peripheral bundle branch block of genesis of the QRS pattern by right ventricular hypertrophy.", "contents": "Alterations of right ventricular systolic time intervals by chronic pressure and volume overloading. Right ventricular (RV) systolic time intervals and hemodynamic parameters were determined by micromanometric techniques in 13 subjects with normal right ventricles (NRV). These data were compared to those of 16 patients with pulmonary hypertension (PH) or predominant pressure overloading and 13 individuals with uncomplicated secundum atrial septal defects (ASD) or predominant volume overloading. In PH, the QP2 interval tends to remain within the normal range due to reciprocal changes in isovolumic contraction (ICT) and ejection (RVET) times. Elevations of pulmonary artery diastolic pressure are associated with increases in the mean rate of isovolumic pressure rise (MRIPR) (r = 0.84), but the latter change does not fully compensate for the widened ventriculoarterial diastolic pressure difference and ICT becomes prolonged (P less than 0.001). Factors other than stroke index depression which may contribute to the decreased duration of RVET (P less than 0.001) include tricuspid regurgitation and elevation of pulmonary vascular impedance. In ASD, QP2 is significantly prolonged (P less than 0.025) due to a significant increase in RVET (P less than 0.005). In contrast to NRV, a linear correlation of RVET and stroke index was not present, which suggested an alteration of ejection dynamics in this group. Despite a high incidence of complete or incomplete right bundle branch block the interval from QRS onset to rapid RV pressure upstroke was not prolonged. This is most probably the result of peripheral bundle branch block of genesis of the QRS pattern by right ventricular hypertrophy."} {"id": "PMID:1269146", "title": "Identification of ethylmalonic acid in urine of two patients with the vomitting sickness of Jamaica.", "content": "Large amounts of ethylmalonic acid have been identified in urines from two patients with the vomitting sickness of Jamaica. The amounts were 178 and 882 mug per mg creatinine which are 70 and 350 times, respectively, over control values. Other short and medium chain dicarboxylic acids including glutaric and adipic acids and those with eight and ten carbon chain, saturated and cis-unsaturated, were also detected in large quantities as in the case of hypoglycin treated rats; urine. However, the large increase of urinary ethylmalonic acid in these two human cases is in a sharp contrast to the findings in hypoglycin treated rats in which urinary ethylmalonic acid increased only 3 times over control. It appears that ethylmalonic acid is produced in the cases with the vomiting sickness of Jamaica by carboxylation of n-butyryl-CoA which is not oxidized further due to the inhibition by hypoglycin A. In case of hypoglycin-treated rats, n-butyryl-CoA is mainly conjugated with glycine or deacylated to free butyric acid.", "contents": "Identification of ethylmalonic acid in urine of two patients with the vomitting sickness of Jamaica. Large amounts of ethylmalonic acid have been identified in urines from two patients with the vomitting sickness of Jamaica. The amounts were 178 and 882 mug per mg creatinine which are 70 and 350 times, respectively, over control values. Other short and medium chain dicarboxylic acids including glutaric and adipic acids and those with eight and ten carbon chain, saturated and cis-unsaturated, were also detected in large quantities as in the case of hypoglycin treated rats; urine. However, the large increase of urinary ethylmalonic acid in these two human cases is in a sharp contrast to the findings in hypoglycin treated rats in which urinary ethylmalonic acid increased only 3 times over control. It appears that ethylmalonic acid is produced in the cases with the vomiting sickness of Jamaica by carboxylation of n-butyryl-CoA which is not oxidized further due to the inhibition by hypoglycin A. In case of hypoglycin-treated rats, n-butyryl-CoA is mainly conjugated with glycine or deacylated to free butyric acid."} {"id": "PMID:1269147", "title": "Double sequential counterimmunoelectrophoresis (DCIEP): an improved method for detection of hepatitis-B antigen (HBAg).", "content": "A method is described for increasing the sensitivity of conventional counterimmunoelectrophoresis (CIEP), i.e. double sequential counterimmunoelectrophoresis (DCIEP). Our method consists of a second electrophoretic migration made after the classical CIEP, where instead of HB antibody (from polytransfused patients), the anodic wells are filled with an antihuman-gammaglobulin antiserum. DCIEP is significantly more sensitive than CIEP (P less than 0.01), the number of positive sera in chronic lever diseases being 28.7% compared with 17.5%.", "contents": "Double sequential counterimmunoelectrophoresis (DCIEP): an improved method for detection of hepatitis-B antigen (HBAg). A method is described for increasing the sensitivity of conventional counterimmunoelectrophoresis (CIEP), i.e. double sequential counterimmunoelectrophoresis (DCIEP). Our method consists of a second electrophoretic migration made after the classical CIEP, where instead of HB antibody (from polytransfused patients), the anodic wells are filled with an antihuman-gammaglobulin antiserum. DCIEP is significantly more sensitive than CIEP (P less than 0.01), the number of positive sera in chronic lever diseases being 28.7% compared with 17.5%."} {"id": "PMID:1269148", "title": "Comparative study of two methods for hepatitis B antigen (HBAg) detection: double sequential counterimmunoelectrophoresis (DCIEP) and Ausria II-125I radioimmunoassay.", "content": "Double sequential counterimmunoelectrophoresis (DCIEP) (an improved method that we have developed) and Ausria II-125I (an indirect solid-phase radioimmunoassay) were compared for HBAg detection in chronic liver diseases. 26.8% of the patients were positive using DCIEP and 41.8% were positive with Ausria II125I. The conventional counterimmunoelectrophoresis (CIEP) is less sensitive than DCIEP, the level of positive results being 18.8% (P less than 0.001)9", "contents": "Comparative study of two methods for hepatitis B antigen (HBAg) detection: double sequential counterimmunoelectrophoresis (DCIEP) and Ausria II-125I radioimmunoassay. Double sequential counterimmunoelectrophoresis (DCIEP) (an improved method that we have developed) and Ausria II-125I (an indirect solid-phase radioimmunoassay) were compared for HBAg detection in chronic liver diseases. 26.8% of the patients were positive using DCIEP and 41.8% were positive with Ausria II125I. The conventional counterimmunoelectrophoresis (CIEP) is less sensitive than DCIEP, the level of positive results being 18.8% (P less than 0.001)9"} {"id": "PMID:1269150", "title": "A rapid method for the measurement of plasma glucose concentration.", "content": "A modification of the manual glucose oxidase-gum guaiacum method of Shipton, B., Wood, P.J. and Marks, V. ((1975) Med. Lab. Tech. 32,33), for use with plasma, is described. The method enables rapid measurement of plasma or serum glucose concentration between 1 and 22 mumol/1 using 10 mul of sample and a single colour reagent. Experience of the method in routine use has shown that the coefficient of variation, beteen batch, is 2.1% and the time taken for analysis of 1 sample, standards and a quality of control sample is 12 min (including centrifugation of blood to obtain plasma).", "contents": "A rapid method for the measurement of plasma glucose concentration. A modification of the manual glucose oxidase-gum guaiacum method of Shipton, B., Wood, P.J. and Marks, V. ((1975) Med. Lab. Tech. 32,33), for use with plasma, is described. The method enables rapid measurement of plasma or serum glucose concentration between 1 and 22 mumol/1 using 10 mul of sample and a single colour reagent. Experience of the method in routine use has shown that the coefficient of variation, beteen batch, is 2.1% and the time taken for analysis of 1 sample, standards and a quality of control sample is 12 min (including centrifugation of blood to obtain plasma)."} {"id": "PMID:1269152", "title": "Cartilage collagen in osteoarthrosis.", "content": "Pronase digestion of osteoarthrotic cartilage collagen indicated that this type of pathological collagenous structure is more susceptible to proteolytic degradation than human controls or bovine and calf articular cartilage. There were some differences between individual patients in the collagen susceptibility to pronase cleavage. Also, different zones of the same diseased femoral head exhibited varied susceptibility. It is suggested that changes in collagen stability are reflected in cartilage permeability and in this way also in alterations in the supply of nutrients.", "contents": "Cartilage collagen in osteoarthrosis. Pronase digestion of osteoarthrotic cartilage collagen indicated that this type of pathological collagenous structure is more susceptible to proteolytic degradation than human controls or bovine and calf articular cartilage. There were some differences between individual patients in the collagen susceptibility to pronase cleavage. Also, different zones of the same diseased femoral head exhibited varied susceptibility. It is suggested that changes in collagen stability are reflected in cartilage permeability and in this way also in alterations in the supply of nutrients."} {"id": "PMID:1269153", "title": "Dopamine-beta-hydroxylase activity in serum following acute myocardial infarction: an evaluation of this parameter for routine use as an index of sympathetic activity.", "content": "Dopamine-beta-hydroxylase activity was measured in sera from 114 normal males and from 11 patients on the 1st, 2nd, 3rd, 5th and 10th day following acute myocardial infarction. A significant elevation of dopamine-beta-hydroxylase levels (P less than 0.001) was found during the first two days after infarction when compared with the 10th-day values. Only a few activities were above the reference range. Temporary elevations of glucose and glycerol levels were also found. Assay of serum dopamine-beta-hydroxylase may be a useful parameter of sympathetic activity in longitudinal studies in which each individual is used as his own reference.", "contents": "Dopamine-beta-hydroxylase activity in serum following acute myocardial infarction: an evaluation of this parameter for routine use as an index of sympathetic activity. Dopamine-beta-hydroxylase activity was measured in sera from 114 normal males and from 11 patients on the 1st, 2nd, 3rd, 5th and 10th day following acute myocardial infarction. A significant elevation of dopamine-beta-hydroxylase levels (P less than 0.001) was found during the first two days after infarction when compared with the 10th-day values. Only a few activities were above the reference range. Temporary elevations of glucose and glycerol levels were also found. Assay of serum dopamine-beta-hydroxylase may be a useful parameter of sympathetic activity in longitudinal studies in which each individual is used as his own reference."} {"id": "PMID:1269155", "title": "Diluted human serum as a suitable diluent in the preparation of bilirubin reference solutions.", "content": "From a concentrated solution of bilirubin in dimethylsulfoxide (about 13 mmol/1, standardized spectrophotometrically) and a serum diluted 1/3 (whose native bilirubin is lowered by exposure to phototherapy lamps) a bilirubin-enriched serum is prepared (bilirubin concentration about 130 mumol/1 = 7.5 mg/dl) wherein all the bilrubin is bound to albumin. Such an enriched serum behaves in the diazo-reaction in the same way as a bilirubin-enriched serum prepared with undiluted serum and can, therefore, be used as a working standard in serum bilirubin assays.", "contents": "Diluted human serum as a suitable diluent in the preparation of bilirubin reference solutions. From a concentrated solution of bilirubin in dimethylsulfoxide (about 13 mmol/1, standardized spectrophotometrically) and a serum diluted 1/3 (whose native bilirubin is lowered by exposure to phototherapy lamps) a bilirubin-enriched serum is prepared (bilirubin concentration about 130 mumol/1 = 7.5 mg/dl) wherein all the bilrubin is bound to albumin. Such an enriched serum behaves in the diazo-reaction in the same way as a bilirubin-enriched serum prepared with undiluted serum and can, therefore, be used as a working standard in serum bilirubin assays."} {"id": "PMID:1269156", "title": "A critical examination of the value of combined determinations of lecithin:cholesterol acyltransferase and lipoprotein-X in the differential diagnosis of liver disease.", "content": "The suggestion that combined determinations of lecithin: cholesterol acyltransferase activity and lipoprotein-X can be used to distinguish between patients with intrahepatic cholestasis and extrahepatic biliary obstruction has been studied. Of 21 patients who were lipoprotein-X positive and in whom an unequivocal diagnosis was made, 11 had intrahepatic cholestasis and 10 extrahepatic obstruction. The range of plasma lecithin:cholesterol acyltransferase activity was similar in the two groups and did not enable distinction to be made between them.", "contents": "A critical examination of the value of combined determinations of lecithin:cholesterol acyltransferase and lipoprotein-X in the differential diagnosis of liver disease. The suggestion that combined determinations of lecithin: cholesterol acyltransferase activity and lipoprotein-X can be used to distinguish between patients with intrahepatic cholestasis and extrahepatic biliary obstruction has been studied. Of 21 patients who were lipoprotein-X positive and in whom an unequivocal diagnosis was made, 11 had intrahepatic cholestasis and 10 extrahepatic obstruction. The range of plasma lecithin:cholesterol acyltransferase activity was similar in the two groups and did not enable distinction to be made between them."} {"id": "PMID:1269157", "title": "A note on the practical aspects of the assay of N-acetyl-beta-glucosaminidase in human urine.", "content": "1. Some practical aspects of the assay of urinary N-acetyl-beta-glucosaminidase activity were studied in patients with renal disease. 2. Centrifugation and dialysis of urine were not necessary prior to assay. 3. When enzyme activity was related to urinary creatinine random urine samples could be used. 4. Since preservatives used to prevent bacterial growth may inhibit enzyme activities, samples should be assayed immediately after collection or stored at 4 degrees C or 20 degrees C. 5. Mild visible haemoglobinuria, eg. derived from lysed red blood cells did not interfere with the enzyme assay.", "contents": "A note on the practical aspects of the assay of N-acetyl-beta-glucosaminidase in human urine. 1. Some practical aspects of the assay of urinary N-acetyl-beta-glucosaminidase activity were studied in patients with renal disease. 2. Centrifugation and dialysis of urine were not necessary prior to assay. 3. When enzyme activity was related to urinary creatinine random urine samples could be used. 4. Since preservatives used to prevent bacterial growth may inhibit enzyme activities, samples should be assayed immediately after collection or stored at 4 degrees C or 20 degrees C. 5. Mild visible haemoglobinuria, eg. derived from lysed red blood cells did not interfere with the enzyme assay."} {"id": "PMID:1269158", "title": "Effect of epidural analgesia on the glycoregulatory endocrine response to surgery.", "content": "Plasma concentrations of glucose, insulin, glucagon, cortisol, growth hormone and prolactin were measured repeatedly in ten females undergoing abdominal hysterectomy during general anaesthesia. In addition to general anaesthesia five of the patients had continuous epidural analgesia effective for the first 26 postoperative hours. Plasma glucose was elevated during surgery and postoperatively, but not in patients having epidural analgesia. Insulin was low and unchanged in both groups. Glucagon was unchanged and similar in both groups. Cortisol was lower during surgery in the epidural group, but not postoperatively. Growth hormone increased during surgery in four of five patients receiving general anaesthesia alone, but no changes were observed in the epidural group. Prolactin was greatly elevated in all patients immediately after induction of anaesthesia and then fell rapidly during surgery, similarly in both groups. It is concluded that epidural analgesia can inhibit the hyperglycaemic response to surgical stress, but this effect cannot be uniformly correlated to changes in peripheral plasma levels of insulin, glucagon, cortisol, growth hormone or prolactin.", "contents": "Effect of epidural analgesia on the glycoregulatory endocrine response to surgery. Plasma concentrations of glucose, insulin, glucagon, cortisol, growth hormone and prolactin were measured repeatedly in ten females undergoing abdominal hysterectomy during general anaesthesia. In addition to general anaesthesia five of the patients had continuous epidural analgesia effective for the first 26 postoperative hours. Plasma glucose was elevated during surgery and postoperatively, but not in patients having epidural analgesia. Insulin was low and unchanged in both groups. Glucagon was unchanged and similar in both groups. Cortisol was lower during surgery in the epidural group, but not postoperatively. Growth hormone increased during surgery in four of five patients receiving general anaesthesia alone, but no changes were observed in the epidural group. Prolactin was greatly elevated in all patients immediately after induction of anaesthesia and then fell rapidly during surgery, similarly in both groups. It is concluded that epidural analgesia can inhibit the hyperglycaemic response to surgical stress, but this effect cannot be uniformly correlated to changes in peripheral plasma levels of insulin, glucagon, cortisol, growth hormone or prolactin."} {"id": "PMID:1269159", "title": "Further observations on postpartum ovarian refractoriness: effect of gonadal stimulation in women receiving bromocryptine.", "content": "It has been reported previously that the administration of human menopausal gonadotrophins (HMG) to lactating and non-lactating women from day 5 to day 9 postpartum elicited no significant elevation of urinary oestrogens or serum oestradiol within 15 days after delivery. In order to study further the role of prolactin on this ovarian refractoriness, five women receiving 7-5 mg of bromocryptine (CB-154) daily were given HMG at a dose of 300 iu per day, from day 5 to day 10 post-delivery. In all women serum oestradiol and urinary oestrogens showed no significant elevation within the 2 weeks after delivery. Serum prolactin was elevated in all cases and fell to normal nonpregnant levels immediately after CB-154 was administered. The suggestion that prolactin may possess antigonadotrophic activity at the ovarian level is not supported by the data presented here. The deficient ovarian response to gonadotrophin stimulation could be due to either the intraovarian effect of the high amounts of circulating steroids produced during gestation or to some unknown mechanism.", "contents": "Further observations on postpartum ovarian refractoriness: effect of gonadal stimulation in women receiving bromocryptine. It has been reported previously that the administration of human menopausal gonadotrophins (HMG) to lactating and non-lactating women from day 5 to day 9 postpartum elicited no significant elevation of urinary oestrogens or serum oestradiol within 15 days after delivery. In order to study further the role of prolactin on this ovarian refractoriness, five women receiving 7-5 mg of bromocryptine (CB-154) daily were given HMG at a dose of 300 iu per day, from day 5 to day 10 post-delivery. In all women serum oestradiol and urinary oestrogens showed no significant elevation within the 2 weeks after delivery. Serum prolactin was elevated in all cases and fell to normal nonpregnant levels immediately after CB-154 was administered. The suggestion that prolactin may possess antigonadotrophic activity at the ovarian level is not supported by the data presented here. The deficient ovarian response to gonadotrophin stimulation could be due to either the intraovarian effect of the high amounts of circulating steroids produced during gestation or to some unknown mechanism."} {"id": "PMID:1269160", "title": "Case of hyperthyroidism due to a chromophobe adenoma.", "content": "A A 23-year-old man with secondary hypogonadism was also found to be thyrotoxic. Results of thyroid function tests were in the hyperthyroid range but the serum TSH was inappropriately high. A pituitary tumour was demonstrated and following hypophysectomy he became biochemically hypothyroid. Evidence is presented and discussed that his hyperthyroidism was due to excessive TSH production by the pituitary tumour.", "contents": "Case of hyperthyroidism due to a chromophobe adenoma. A A 23-year-old man with secondary hypogonadism was also found to be thyrotoxic. Results of thyroid function tests were in the hyperthyroid range but the serum TSH was inappropriately high. A pituitary tumour was demonstrated and following hypophysectomy he became biochemically hypothyroid. Evidence is presented and discussed that his hyperthyroidism was due to excessive TSH production by the pituitary tumour."} {"id": "PMID:1269161", "title": "Total thyroidal content of iodine in thyrotoxic patients measured by in vivo neutron activation analysis.", "content": "This paper describes an in vivo method for measuring total thyroidal iodine stores by activation analysis, its evaluation and measurements in thyrotoxic patients. There was good correlation between measurements of solutions of iodine and post-mortem thyroids by activation analysis and chemical analysis. Measurements in thyrotoxic patients showed low levels in untreated and treated (antithyroid drugs) patients and a marked increase in patients studied whilst in clinical remission. The practical importance of this method of measurement of thyroidal iodine stores is that it is a reliable in vivo measurement obtained at a single visit and should enable the definition of the relationship of thyroidal iodine stores to pathophysiology and prognosis.", "contents": "Total thyroidal content of iodine in thyrotoxic patients measured by in vivo neutron activation analysis. This paper describes an in vivo method for measuring total thyroidal iodine stores by activation analysis, its evaluation and measurements in thyrotoxic patients. There was good correlation between measurements of solutions of iodine and post-mortem thyroids by activation analysis and chemical analysis. Measurements in thyrotoxic patients showed low levels in untreated and treated (antithyroid drugs) patients and a marked increase in patients studied whilst in clinical remission. The practical importance of this method of measurement of thyroidal iodine stores is that it is a reliable in vivo measurement obtained at a single visit and should enable the definition of the relationship of thyroidal iodine stores to pathophysiology and prognosis."} {"id": "PMID:1269162", "title": "Maternal thyroid function, iodine deficiency and fetal development.", "content": "In an area of New Guinea where there is dietary iodine deficiency, measurements of thyroid function have been made on women of child-bearing age, several of whom were pregnant at the time. The outcome of these pregnancies, and also of those occurring in the four preceding years, were examined in relation to indices of thyroid function. More stillbirths, infant deaths and endemic cretins occurred among the offspring of women who showed biochemical evidence of iodine deficiency, without clinical evidence of hypothyroidism. This situation differs from that of untreated myxoedema or congenital hypothyroidism in women, which is usually associated with altered menstrual function, infertility or repeated abortion. Mechanisms that may account for these differences and the possible implications are discussed.", "contents": "Maternal thyroid function, iodine deficiency and fetal development. In an area of New Guinea where there is dietary iodine deficiency, measurements of thyroid function have been made on women of child-bearing age, several of whom were pregnant at the time. The outcome of these pregnancies, and also of those occurring in the four preceding years, were examined in relation to indices of thyroid function. More stillbirths, infant deaths and endemic cretins occurred among the offspring of women who showed biochemical evidence of iodine deficiency, without clinical evidence of hypothyroidism. This situation differs from that of untreated myxoedema or congenital hypothyroidism in women, which is usually associated with altered menstrual function, infertility or repeated abortion. Mechanisms that may account for these differences and the possible implications are discussed."} {"id": "PMID:1269163", "title": "A comparison of the effect of levodopa and somatostatin on the plasma levels of growth hormone, insulin, glucagon and prolactin in acromegaly.", "content": "The acute suppressive effects of L-dopa and somatostatin (growth hormone release inhibiting hormone) on the elevated plasma GH concentrations of seven patients with acromegaly were compared. In addition the effects of the two agents on fasting concentrations of plasma glucose, insulin, glucagon and prolactin were studied. In six of the seven patients hourly samples for GH assay were taken from 08.00 to 20.00 hours on a control day. Synthetic cyclic somatostatin (100 mug) was infused intravenously in an albumin/saline solution over 75 min with a Harvard constant infusion pump. Levodopa 500 mg was given orally. Somatostatin infusion produced a reduction in plasma GH concentrations in six of seven patients (mean reduction 55%). L-Dopa produced a reduction in plasma GH concentrations in the same six patients (mean reduction 52%). The minimum GH concentrations achieved in the two tests were comparable and did not differ significantly from the minimum GH concentrations recorded during the 12 h control study. Mean plasma insulin and glucagon concentrations were also significantly reduced during the somatostatin infusion (P less than 0-025; P less than 0-05 respectively). Plasma glucose concentrations did not change. L-Dopa did not alter mean plasma glucose, insulin or glucagon values. Somatostatin did not alter prolactin values but L-Dopa suppressed basal values to less than 2 ng/ml in five patients. This study shows that the plasma GH change after the administration of L-dopa and somatostatin in acromegaly is comparable and confirms the pancreatic effects of somatostatin.", "contents": "A comparison of the effect of levodopa and somatostatin on the plasma levels of growth hormone, insulin, glucagon and prolactin in acromegaly. The acute suppressive effects of L-dopa and somatostatin (growth hormone release inhibiting hormone) on the elevated plasma GH concentrations of seven patients with acromegaly were compared. In addition the effects of the two agents on fasting concentrations of plasma glucose, insulin, glucagon and prolactin were studied. In six of the seven patients hourly samples for GH assay were taken from 08.00 to 20.00 hours on a control day. Synthetic cyclic somatostatin (100 mug) was infused intravenously in an albumin/saline solution over 75 min with a Harvard constant infusion pump. Levodopa 500 mg was given orally. Somatostatin infusion produced a reduction in plasma GH concentrations in six of seven patients (mean reduction 55%). L-Dopa produced a reduction in plasma GH concentrations in the same six patients (mean reduction 52%). The minimum GH concentrations achieved in the two tests were comparable and did not differ significantly from the minimum GH concentrations recorded during the 12 h control study. Mean plasma insulin and glucagon concentrations were also significantly reduced during the somatostatin infusion (P less than 0-025; P less than 0-05 respectively). Plasma glucose concentrations did not change. L-Dopa did not alter mean plasma glucose, insulin or glucagon values. Somatostatin did not alter prolactin values but L-Dopa suppressed basal values to less than 2 ng/ml in five patients. This study shows that the plasma GH change after the administration of L-dopa and somatostatin in acromegaly is comparable and confirms the pancreatic effects of somatostatin."} {"id": "PMID:1269164", "title": "Plasma dopamine-beta-hydroxylase activity in phaeochromocytoma.", "content": "Plasma dopamine-beta-hydroxylase (DbetaH) activity, a marker of catecholamine secretion that occurs via exocytosis, was determined preoperatively in eight patients with phaeochromocytoma. Despite very elevated urinary catecholamine concentrations, mean plasma DbetaH activity was 32-6 +/- 3 u/l and was not significantly different from apparently healthy subjects. Seven days after surgery, one subject exhibited a 60% postoperative decrease of enzyme activity. These results suggest that diffusion across plasma membranes is the predominant mechanism of catecholamine release from phaeochromocytomas. The postoperative change in one patient suggests tumour heterogeneity and that exocytosis may contribute to the process of catecholamine release in some patients.", "contents": "Plasma dopamine-beta-hydroxylase activity in phaeochromocytoma. Plasma dopamine-beta-hydroxylase (DbetaH) activity, a marker of catecholamine secretion that occurs via exocytosis, was determined preoperatively in eight patients with phaeochromocytoma. Despite very elevated urinary catecholamine concentrations, mean plasma DbetaH activity was 32-6 +/- 3 u/l and was not significantly different from apparently healthy subjects. Seven days after surgery, one subject exhibited a 60% postoperative decrease of enzyme activity. These results suggest that diffusion across plasma membranes is the predominant mechanism of catecholamine release from phaeochromocytomas. The postoperative change in one patient suggests tumour heterogeneity and that exocytosis may contribute to the process of catecholamine release in some patients."} {"id": "PMID:1269165", "title": "Assessment by continuous cardiac monitoring of minimum duration of preoperative propranolol treatment in thyrotoxic patients.", "content": "The effect of the beta-blocker, propranolol (40 mg 6-hourly orally) has been studied on the tachycardia of six patients with untreated thyrotoxicosis. Heart rate was monitored continuously using a light portable ECG recorder which allowed the patients to undertake normal activities during the recording periods. The most marked reduction in heart rate was evident at 24 h after starting propranolol treatment. In three of the patients there was only a minor further fall in heart rate despite continued propranolol administration, but in the remaining patients the reduction in heart rate with each successive day of treatment was more marked. These results suggest that if propranolol were to be used alone in the preparation of patients before partial thyroidectomy for thyrotoxicosis, a dose of 40 mg 6-hourly for 3-4 days might be sufficient.", "contents": "Assessment by continuous cardiac monitoring of minimum duration of preoperative propranolol treatment in thyrotoxic patients. The effect of the beta-blocker, propranolol (40 mg 6-hourly orally) has been studied on the tachycardia of six patients with untreated thyrotoxicosis. Heart rate was monitored continuously using a light portable ECG recorder which allowed the patients to undertake normal activities during the recording periods. The most marked reduction in heart rate was evident at 24 h after starting propranolol treatment. In three of the patients there was only a minor further fall in heart rate despite continued propranolol administration, but in the remaining patients the reduction in heart rate with each successive day of treatment was more marked. These results suggest that if propranolol were to be used alone in the preparation of patients before partial thyroidectomy for thyrotoxicosis, a dose of 40 mg 6-hourly for 3-4 days might be sufficient."} {"id": "PMID:1269166", "title": "Trisomy of chromosome 20.", "content": "A neonate with ususual facial features and multiple congenital malformations expired at 4 hours of age. An autopsy revealed severe anomalies of the gastrointestinal system and spinal dysplasia. Cytogenetic evaluation of fibroblasts cultured from a lung biopsy revealed a karyotope of 47,XX,+20.", "contents": "Trisomy of chromosome 20. A neonate with ususual facial features and multiple congenital malformations expired at 4 hours of age. An autopsy revealed severe anomalies of the gastrointestinal system and spinal dysplasia. Cytogenetic evaluation of fibroblasts cultured from a lung biopsy revealed a karyotope of 47,XX,+20."} {"id": "PMID:1269167", "title": "An extra small metacentric chromosome identified as a deleted chromosome no. 17.", "content": "In an 11-year-old girl with multiple congenital abnormalities and mental retardation, an extra, small, metacentric chromosome was identified by banding methods as a deleted chromosome No. 17. This represents the first reported case of partial trisomy 17.", "contents": "An extra small metacentric chromosome identified as a deleted chromosome no. 17. In an 11-year-old girl with multiple congenital abnormalities and mental retardation, an extra, small, metacentric chromosome was identified by banding methods as a deleted chromosome No. 17. This represents the first reported case of partial trisomy 17."} {"id": "PMID:1269168", "title": "Familial carcinoma of the pancreas.", "content": "A sibship is reported in which four brothers died of adenocarcinoma of the pancreas in the seventh or eighth decade of life. None of the patients had a history of pancreatitis, other malignant neoplasms, or exposure to a known pancreatic carcinogen. This family seems to exhibit a genetic predisposition to pancreatic carcinoma late in life, but the mode of inheritance and the relative importance of genetic and environmental factors in the development of these tumors are unclear.", "contents": "Familial carcinoma of the pancreas. A sibship is reported in which four brothers died of adenocarcinoma of the pancreas in the seventh or eighth decade of life. None of the patients had a history of pancreatitis, other malignant neoplasms, or exposure to a known pancreatic carcinogen. This family seems to exhibit a genetic predisposition to pancreatic carcinoma late in life, but the mode of inheritance and the relative importance of genetic and environmental factors in the development of these tumors are unclear."} {"id": "PMID:1269169", "title": "The genetics of and associated clinical findings in humero-radial synostosis.", "content": "This paper compares the manifestations of sporadic, dominantly inherited and recessively inherited humero-radial synostosis with the aim of determining ways of separating these forms on clinical grounds. The genetic forms are characterized by bilateral involvement and by lack of the distal ulnar malformations and the absence of digits that are common in the sporadic cases. The majority of patients with the dominantly inherited form have a characteristic pattern of anomalies, including brachymesophalangy, and the recessive cases have a high frequency of malformations in addition to those of the limbs. Consanguinity is frequent in the families of recessive cases. Four additional patients are presented; two of them illustrate many of the features of the phocomelic syndrome reported by Herrmann et al. (1969). A possible teratogenic cause of these cases is discussed.", "contents": "The genetics of and associated clinical findings in humero-radial synostosis. This paper compares the manifestations of sporadic, dominantly inherited and recessively inherited humero-radial synostosis with the aim of determining ways of separating these forms on clinical grounds. The genetic forms are characterized by bilateral involvement and by lack of the distal ulnar malformations and the absence of digits that are common in the sporadic cases. The majority of patients with the dominantly inherited form have a characteristic pattern of anomalies, including brachymesophalangy, and the recessive cases have a high frequency of malformations in addition to those of the limbs. Consanguinity is frequent in the families of recessive cases. Four additional patients are presented; two of them illustrate many of the features of the phocomelic syndrome reported by Herrmann et al. (1969). A possible teratogenic cause of these cases is discussed."} {"id": "PMID:1269171", "title": "Congenital generalized fibromatosis: an autosomal recessive condition?", "content": "Congenital generalized fibromatosis is a rare condition which is often misdiagnosed and given an erroneously poor prognosis. Five new cases are presented in this report, all initially having been diagnosed as neurofibromatosis. The histopathological findings are presented and the differential diagnosis is discussed. The natural history of the disorder appears to include an initial phase of proliferation soon after birth with appearance of new tumor masses. Providing these do not involve vital viscera, the patient survives with regression and eventual disappearance of all lesions. Spontaneous regression occurred in all five patients reported. Two sets of sibs occurred in the cases described. The possible genetic aspects of this are discussed and the pertinent literature reviewed.", "contents": "Congenital generalized fibromatosis: an autosomal recessive condition? Congenital generalized fibromatosis is a rare condition which is often misdiagnosed and given an erroneously poor prognosis. Five new cases are presented in this report, all initially having been diagnosed as neurofibromatosis. The histopathological findings are presented and the differential diagnosis is discussed. The natural history of the disorder appears to include an initial phase of proliferation soon after birth with appearance of new tumor masses. Providing these do not involve vital viscera, the patient survives with regression and eventual disappearance of all lesions. Spontaneous regression occurred in all five patients reported. Two sets of sibs occurred in the cases described. The possible genetic aspects of this are discussed and the pertinent literature reviewed."} {"id": "PMID:1269172", "title": "Lysosomal enzyme levels in human amniotic fluid cells in tissue culture. IV. %A N-acetyl-beta-D-glucosaminidase.", "content": "Total and % A hexosaminidase were similar for primary cultures and later passages of amniotic fluid cells. The culture variables-through serial passage, within a passage and replicate primary cultures-resulted in some variation in total hexosaminidase, but an insignificant change in % A hexosaminidase. They are unlikely to give rise to any problems in the antenatal diagnosis of Sandhoff's and Tay-Sachs diseases.", "contents": "Lysosomal enzyme levels in human amniotic fluid cells in tissue culture. IV. %A N-acetyl-beta-D-glucosaminidase. Total and % A hexosaminidase were similar for primary cultures and later passages of amniotic fluid cells. The culture variables-through serial passage, within a passage and replicate primary cultures-resulted in some variation in total hexosaminidase, but an insignificant change in % A hexosaminidase. They are unlikely to give rise to any problems in the antenatal diagnosis of Sandhoff's and Tay-Sachs diseases."} {"id": "PMID:1269174", "title": "Analbuminemia in an American Indian girl.", "content": "Analbuminemia was fortuitously detected in a nonedematous 12-year-old American Indian girl with atopic dermatitis, mild bronchial asthma, a mild seizure disorder, and hyperlipoproteinemia with a corneal arcus. Immunologic methods revealed trace amounts (17 mg/100 ml) of apparently normal serum albumin. The patient's parents were remotely related. The pedigree and clinical findings were compatible with autosomal recessive transmission of analbuminemia. Heterozygotes had subnormal levels of serum albumin. The Gc-locus is closely linked to the structural albumin locus. Gc-protein levels were normal in the patient and together with normal chromosomal banding studies make it unlikely that a chromosomal deletion caused analbuminemia. Gc-types in the family were compatible with, but did not prove, linkage of analbuminemia to the Gc-locus. These findings suggest a \"thalassemia\"-like mutation for this disorder.", "contents": "Analbuminemia in an American Indian girl. Analbuminemia was fortuitously detected in a nonedematous 12-year-old American Indian girl with atopic dermatitis, mild bronchial asthma, a mild seizure disorder, and hyperlipoproteinemia with a corneal arcus. Immunologic methods revealed trace amounts (17 mg/100 ml) of apparently normal serum albumin. The patient's parents were remotely related. The pedigree and clinical findings were compatible with autosomal recessive transmission of analbuminemia. Heterozygotes had subnormal levels of serum albumin. The Gc-locus is closely linked to the structural albumin locus. Gc-protein levels were normal in the patient and together with normal chromosomal banding studies make it unlikely that a chromosomal deletion caused analbuminemia. Gc-types in the family were compatible with, but did not prove, linkage of analbuminemia to the Gc-locus. These findings suggest a \"thalassemia\"-like mutation for this disorder."} {"id": "PMID:1269175", "title": "Cystic fibrosis: a cell culture study on an adult patient population.", "content": "Skin fibroblast cultures from an adult population of cystic fibrosis (CF) patients have been studied to determine any possible genetic or clinical significance of the two classes described for cultured CF skin fibroblasts (Danes 1973). On the basis of clinical course, the 46 adult patients from 43 unrelated families studied were divided into two groups (40 typical, 6 atypical). The cultured fibroblasts from 37 of the 40 patients with typical CF were Class I (metachromatic, cystic fibrosis factor activity (CFFA) in the culture medium, and metabolic cooperation with normal fibroblasts), and the cultures from the remaining three patients were Class II (ametachromatic, no CFFA in the culture medium and no metabolic cooperation with metachromatic CF fibroblasts). During the 4-year research period one of the 37 patients from Class I and all three Class II patients with typical CF succumbed. The cultured skin fibroblasts from two of the six patients who had an atypical course for CF were Class I and four were Class II. When the parents of three of these atypical CF Class II patients were studied, the cultured fibroblasts from one parent in each family in each family were Class I and the other Class II. The affected offspring from such Class I-II matings may represent genetic compounds.", "contents": "Cystic fibrosis: a cell culture study on an adult patient population. Skin fibroblast cultures from an adult population of cystic fibrosis (CF) patients have been studied to determine any possible genetic or clinical significance of the two classes described for cultured CF skin fibroblasts (Danes 1973). On the basis of clinical course, the 46 adult patients from 43 unrelated families studied were divided into two groups (40 typical, 6 atypical). The cultured fibroblasts from 37 of the 40 patients with typical CF were Class I (metachromatic, cystic fibrosis factor activity (CFFA) in the culture medium, and metabolic cooperation with normal fibroblasts), and the cultures from the remaining three patients were Class II (ametachromatic, no CFFA in the culture medium and no metabolic cooperation with metachromatic CF fibroblasts). During the 4-year research period one of the 37 patients from Class I and all three Class II patients with typical CF succumbed. The cultured skin fibroblasts from two of the six patients who had an atypical course for CF were Class I and four were Class II. When the parents of three of these atypical CF Class II patients were studied, the cultured fibroblasts from one parent in each family in each family were Class I and the other Class II. The affected offspring from such Class I-II matings may represent genetic compounds."} {"id": "PMID:1269176", "title": "Mucolipidosis II and III: different residual activity of beta-galactosidase in cultured fibroblasts.", "content": "A biochemical difference is found between the mucolipidoses II and III which may be correlated with their clinical phenotypes. In homogenates of mass-cultured I-cells from patients with MLII (I-cell disease), the residual specific activity of beta-galactosidase is between 3 and 5 times lower than that in the I-cells from patients with MLIII (pseudopolydystrophy). This difference is confirmed in several coverslip culture experiments where conditions of inoculation, propagation, harvest and enzyme assays are rigidly controlled. MLIII cells also hydrolyse the natural substrates asialofetuin-(H)3-galactoside and GM1- (H)3-galactoside more easily. This observation offers support to the hypothesis that beta-galactosidase may play a role in the physiopathology of these mucolipidoses.", "contents": "Mucolipidosis II and III: different residual activity of beta-galactosidase in cultured fibroblasts. A biochemical difference is found between the mucolipidoses II and III which may be correlated with their clinical phenotypes. In homogenates of mass-cultured I-cells from patients with MLII (I-cell disease), the residual specific activity of beta-galactosidase is between 3 and 5 times lower than that in the I-cells from patients with MLIII (pseudopolydystrophy). This difference is confirmed in several coverslip culture experiments where conditions of inoculation, propagation, harvest and enzyme assays are rigidly controlled. MLIII cells also hydrolyse the natural substrates asialofetuin-(H)3-galactoside and GM1- (H)3-galactoside more easily. This observation offers support to the hypothesis that beta-galactosidase may play a role in the physiopathology of these mucolipidoses."} {"id": "PMID:1269177", "title": "Segregation within a family of two mutant alleles for hexosaminidase A.", "content": "A healthy adult female was found to have low levels of hexosaminidase A in serum, leukocytes and fibroblasts when these were assayed with artificial substrates. Fibroblast assay with GM2 ganglioside gave values consistent with a Tay-Sachs heterozygote. Studies of this non-Jewish family revealed evidence for segregation of two mutant alleles for hexosaminidase A.", "contents": "Segregation within a family of two mutant alleles for hexosaminidase A. A healthy adult female was found to have low levels of hexosaminidase A in serum, leukocytes and fibroblasts when these were assayed with artificial substrates. Fibroblast assay with GM2 ganglioside gave values consistent with a Tay-Sachs heterozygote. Studies of this non-Jewish family revealed evidence for segregation of two mutant alleles for hexosaminidase A."} {"id": "PMID:1269184", "title": "Behavioral treatment of hyperkinetic children. An experimental evaluation of its usefulness.", "content": "Although drug therapy is helpful in the control of many children with hyperkinesia, alternative and adjunctive therapies are needed also, for a number of reasons: 1) not all of these children improve with medication; 2) the drugs may have adverse physiologic effects which at the least dictate caution in their use; 3) medication alone does not always return responding children to normal functioning; and 4) drug action cannot often be used to help with problems occurring in the children's home setting after school hours. The data here presented suggest strongly that behavior therapy can be effective for hyperkinesia.", "contents": "Behavioral treatment of hyperkinetic children. An experimental evaluation of its usefulness. Although drug therapy is helpful in the control of many children with hyperkinesia, alternative and adjunctive therapies are needed also, for a number of reasons: 1) not all of these children improve with medication; 2) the drugs may have adverse physiologic effects which at the least dictate caution in their use; 3) medication alone does not always return responding children to normal functioning; and 4) drug action cannot often be used to help with problems occurring in the children's home setting after school hours. The data here presented suggest strongly that behavior therapy can be effective for hyperkinesia."} {"id": "PMID:1269187", "title": "The growth and development of low birth weight infants receiving intensive neonatal care. Preliminary observations on 28 such infants.", "content": "This study reports the growth and development of 28 survivors who had a birth weight of less than or equal to 1,000 g and were cared for at a Regional Neonatal Intensive Care Unit. Only eight (30%) had neurologic abnormalities including spastic hemiparesis, retrolental fibroplasia, hydrocephalus, motor retardation, and some delay in language skills. The other survivors had normal physical examinations and developmental progress judged by a variety of screening examinations up to age four years, three months. The average caloric intake during the first week was 61 kg/da, although over half never reached that level until day 4. Nearly all the infants have had standard growth patterns thus far.", "contents": "The growth and development of low birth weight infants receiving intensive neonatal care. Preliminary observations on 28 such infants. This study reports the growth and development of 28 survivors who had a birth weight of less than or equal to 1,000 g and were cared for at a Regional Neonatal Intensive Care Unit. Only eight (30%) had neurologic abnormalities including spastic hemiparesis, retrolental fibroplasia, hydrocephalus, motor retardation, and some delay in language skills. The other survivors had normal physical examinations and developmental progress judged by a variety of screening examinations up to age four years, three months. The average caloric intake during the first week was 61 kg/da, although over half never reached that level until day 4. Nearly all the infants have had standard growth patterns thus far."} {"id": "PMID:1269189", "title": "The practical management of vesicoureteral reflux in children. A review of 12 years' experience with 236 patients.", "content": "Early recognition, adequate treatment, close observation, and systematic follow-up over a long period are essential to renal salvage in the child with vesicoureteral reflux. The decision whether and when to operate is made on a balance of factors by the pediatrician-urologist team. Among 236 patients with reflux diagnosed during childhood, reflux was stopped in 55 per cent of those treated medically and in 98 per cent of the more severe cases who were treated by ureteral reimplantation. Chronic pyelonephritis appeared or worsened during medical management in 12 per cent; no child showed new pyelonephritic scars or worsening of pyelonephritis after ureteral reimplantation.", "contents": "The practical management of vesicoureteral reflux in children. A review of 12 years' experience with 236 patients. Early recognition, adequate treatment, close observation, and systematic follow-up over a long period are essential to renal salvage in the child with vesicoureteral reflux. The decision whether and when to operate is made on a balance of factors by the pediatrician-urologist team. Among 236 patients with reflux diagnosed during childhood, reflux was stopped in 55 per cent of those treated medically and in 98 per cent of the more severe cases who were treated by ureteral reimplantation. Chronic pyelonephritis appeared or worsened during medical management in 12 per cent; no child showed new pyelonephritic scars or worsening of pyelonephritis after ureteral reimplantation."} {"id": "PMID:1269191", "title": "Disposition of digitoxin in renal failure.", "content": "The disposition of digitoxin was studied for a period of 8 days in 6 uremic patients given a single oral dose of 1 mg 3H-digitoxin. In plasma, the time-course of radioactivity indicated a diminished absorption velocity of tritium compared to that of control subjects already reported and, after reaching of a pseudostate-equilibrium at 24 hr, an exponential decline with a mean half-life of 8.0 days. In urine, smaller amounts of tritiated compounds were eliminated in uremic patients (8.7% of the dose) than in controls (22.5%). The average fecal excretion of digitoxin and its metabolites was not significantly increased. Chloroform extraction and thin-layer chromatography in plasma, urine and feces suggested no qualitative alteration in the metabolism of digitoxin. Calculations of the total body tritium content (body stores) after each 24-hr interval and its pharmacokinetic behavior showed that the elimination of digitoxin is determined by the transfer constant from tissue to plasma. The differences in elimination kinetics of digitoxin and its metabolites of uremic patients and healthy subjects were not significant.", "contents": "Disposition of digitoxin in renal failure. The disposition of digitoxin was studied for a period of 8 days in 6 uremic patients given a single oral dose of 1 mg 3H-digitoxin. In plasma, the time-course of radioactivity indicated a diminished absorption velocity of tritium compared to that of control subjects already reported and, after reaching of a pseudostate-equilibrium at 24 hr, an exponential decline with a mean half-life of 8.0 days. In urine, smaller amounts of tritiated compounds were eliminated in uremic patients (8.7% of the dose) than in controls (22.5%). The average fecal excretion of digitoxin and its metabolites was not significantly increased. Chloroform extraction and thin-layer chromatography in plasma, urine and feces suggested no qualitative alteration in the metabolism of digitoxin. Calculations of the total body tritium content (body stores) after each 24-hr interval and its pharmacokinetic behavior showed that the elimination of digitoxin is determined by the transfer constant from tissue to plasma. The differences in elimination kinetics of digitoxin and its metabolites of uremic patients and healthy subjects were not significant."} {"id": "PMID:1269192", "title": "Observations on the pharmacokinetics of acebutolol.", "content": "Using a balance, randomized, crossover design, single intravenous (1 mg/kg) or oral (3 X 100 mg) doses of acebutolol were administered at weekly intervals to 6 healthy volunteers. For each subject venous blood samples and timed urine collections were obtained after each treatment. Plasma and urinary acebutolol levels were measured by a spectrophotometric method that measures acebutolol and its N-acetyl metabolite (which has equivalent cardiac activity). Using a computer program, various pharmacokinetic parameters were estimated from the date of each subject. From the intravenous data (obtained up to 6 hr after dosing), the following mean (+/-SD) values were found: distribution half-life (T 1/2D), 0.60 (+/-0.43) hr, plasma elimination half-life (T 1/2El), 3.2 (+/-1.1) hr, apparent volume of distribution (VD), 224 (+/-69) L, and apparent VD/kg, 3.0 (+/-0.8) L/kg. Using the oral data (obtained up to 10 hr after dosing), the value for T 1/2El was 3.2 (+/-0.9) hr. The mean cumulative urinary recovery (expressed as % dose) after the intravenous route was about 60%, while that after the oral route was of the order of 35%, suggesting that about half of the oral dose reached the systemic circulation. The mean creatinine clearance of the 6 subjects was 103 (+/-7) ml/min, while the value (obtained between 2 and 4 hr after intravenous dosing) for renal clearance of acebutolol as measured was 298 (+/-68) ml/min and the corresponding plasma clearance was 818 (+/-64) ml/min. These results support the occurrence of substantial nonrenal elimination and renal tubular secretion.", "contents": "Observations on the pharmacokinetics of acebutolol. Using a balance, randomized, crossover design, single intravenous (1 mg/kg) or oral (3 X 100 mg) doses of acebutolol were administered at weekly intervals to 6 healthy volunteers. For each subject venous blood samples and timed urine collections were obtained after each treatment. Plasma and urinary acebutolol levels were measured by a spectrophotometric method that measures acebutolol and its N-acetyl metabolite (which has equivalent cardiac activity). Using a computer program, various pharmacokinetic parameters were estimated from the date of each subject. From the intravenous data (obtained up to 6 hr after dosing), the following mean (+/-SD) values were found: distribution half-life (T 1/2D), 0.60 (+/-0.43) hr, plasma elimination half-life (T 1/2El), 3.2 (+/-1.1) hr, apparent volume of distribution (VD), 224 (+/-69) L, and apparent VD/kg, 3.0 (+/-0.8) L/kg. Using the oral data (obtained up to 10 hr after dosing), the value for T 1/2El was 3.2 (+/-0.9) hr. The mean cumulative urinary recovery (expressed as % dose) after the intravenous route was about 60%, while that after the oral route was of the order of 35%, suggesting that about half of the oral dose reached the systemic circulation. The mean creatinine clearance of the 6 subjects was 103 (+/-7) ml/min, while the value (obtained between 2 and 4 hr after intravenous dosing) for renal clearance of acebutolol as measured was 298 (+/-68) ml/min and the corresponding plasma clearance was 818 (+/-64) ml/min. These results support the occurrence of substantial nonrenal elimination and renal tubular secretion."} {"id": "PMID:1269193", "title": "Plasma protein binding and placental transfer of bupivacaine.", "content": "The maternal venous and umbilical venous plasma concentrations of bupivacaine were determined at delivery following epidural administration of the drug to 31 women in labor. In each case the umbilical venous plasma concentration of bupivacaine was lower than the maternal venous plasma concentration. There was no significant difference between the concentration of unbound bupivacaine in umbilical venous and maternal venous plasma at delivery. The difference in umbilical and maternal plasma concentrations of bupivacaine appears to be a consequence of greater bupivacaine binding to maternal than to fetal total plasma protein. The intersubject variation of the ratio of bupivacaine concentration in fetal plasma/bupivacaine concentration in maternal plasma was found to be related to individual variation in the extent of protein binding of bupivacaine in maternal and umbilical plasma and correlated positively with the variation of the ratio of total protein concentration in umbilical and maternal plasma.", "contents": "Plasma protein binding and placental transfer of bupivacaine. The maternal venous and umbilical venous plasma concentrations of bupivacaine were determined at delivery following epidural administration of the drug to 31 women in labor. In each case the umbilical venous plasma concentration of bupivacaine was lower than the maternal venous plasma concentration. There was no significant difference between the concentration of unbound bupivacaine in umbilical venous and maternal venous plasma at delivery. The difference in umbilical and maternal plasma concentrations of bupivacaine appears to be a consequence of greater bupivacaine binding to maternal than to fetal total plasma protein. The intersubject variation of the ratio of bupivacaine concentration in fetal plasma/bupivacaine concentration in maternal plasma was found to be related to individual variation in the extent of protein binding of bupivacaine in maternal and umbilical plasma and correlated positively with the variation of the ratio of total protein concentration in umbilical and maternal plasma."} {"id": "PMID:1269194", "title": "Pharmacokinetics of methotrimeprazine after single and multiple doses.", "content": "Concentrations of methotrimeprazine and a metabolite, methotrimeprazine sulfoxide, were measured in plasma after a single intramuscular dose and after single and multiple oral doses of methotrimeprazine. The highest plasma concentrations of methotrimeprazine were found 30 to 90 min after intramuscular injection, and 1 to 3 hr after oral administration. On average 50% of orally administered drug reached the general circulation as unchanged methotrimeprazine. The apparent volume of distribution (Vbeta) was 23 to 42 L/kg body weight, and the biologic half-life, 15 to 30 hr. The sulfoxide could not be traced in plasma after a 25-mg intramuscular dose, but was found in higher plasma concentrations than the unmetabolized drug after single and multiple oral doses. This could be due to oxidation of the drug either in the gastrointestinal lumen or in the intestinal wall, or during its first passage through the liver. The apparent half-life of the sulfoxide was on average 30% shorter than the half-life of methotrimeprazine.", "contents": "Pharmacokinetics of methotrimeprazine after single and multiple doses. Concentrations of methotrimeprazine and a metabolite, methotrimeprazine sulfoxide, were measured in plasma after a single intramuscular dose and after single and multiple oral doses of methotrimeprazine. The highest plasma concentrations of methotrimeprazine were found 30 to 90 min after intramuscular injection, and 1 to 3 hr after oral administration. On average 50% of orally administered drug reached the general circulation as unchanged methotrimeprazine. The apparent volume of distribution (Vbeta) was 23 to 42 L/kg body weight, and the biologic half-life, 15 to 30 hr. The sulfoxide could not be traced in plasma after a 25-mg intramuscular dose, but was found in higher plasma concentrations than the unmetabolized drug after single and multiple oral doses. This could be due to oxidation of the drug either in the gastrointestinal lumen or in the intestinal wall, or during its first passage through the liver. The apparent half-life of the sulfoxide was on average 30% shorter than the half-life of methotrimeprazine."} {"id": "PMID:1269195", "title": "Biliary elimination of diazepam in man.", "content": "The metabolism of 14C-5-diazepam has been studied in 5 patients with T tube biliary drainage. A single bolus of 40 to 50 muCi was given intravenously and blood, urine, and bile were analyzed from 5 to 14 days. The mean half-life of elimination from blood was 93.2 hr; the major metabolite noted in blood was N-desmethyl-diazepam. In urine the average recovery of radioactivity was 48.9% and consisted of 3 OH-diazepam, 4'OH-diazepam, and oxazepam. In bile the average recovery of radioactivity was 5.35% (corrected to a bile flow of 700 ml was 15.0%) and consisted of the same metabolites as in the urine. Essentially no diazepam or N-desmethyl-diazepam was found, and therefore an enterohepatic circulation cannot be held to account for the prolonged half-life of these substances in man.", "contents": "Biliary elimination of diazepam in man. The metabolism of 14C-5-diazepam has been studied in 5 patients with T tube biliary drainage. A single bolus of 40 to 50 muCi was given intravenously and blood, urine, and bile were analyzed from 5 to 14 days. The mean half-life of elimination from blood was 93.2 hr; the major metabolite noted in blood was N-desmethyl-diazepam. In urine the average recovery of radioactivity was 48.9% and consisted of 3 OH-diazepam, 4'OH-diazepam, and oxazepam. In bile the average recovery of radioactivity was 5.35% (corrected to a bile flow of 700 ml was 15.0%) and consisted of the same metabolites as in the urine. Essentially no diazepam or N-desmethyl-diazepam was found, and therefore an enterohepatic circulation cannot be held to account for the prolonged half-life of these substances in man."} {"id": "PMID:1269196", "title": "Sodium salicylamide: relative bioavailability and subjective effects.", "content": "The bioavailability of sodium salicylamide (NaSAM) in solution of salicylamide (SAM) tablets was compared in 6 healthy human volunteers. Bioavailability was assessed by plasma level determinations of nonmetabolized salicylamide (free SAM) and salicylamide plus conjugated metabolites (total SAM) for 3 hr following oral doses of 0.65, 1.30, 1.95, and 2.60 gm of salicylamide. The availability of NaSAM was found to be superior to SAM and dose-dependent. Mean peak levels of free SAM and total SAM were higher and were reached earlier after NaSAM liquid than after SAM tablets. Significantly higher mean levels of free SAM were found at the 1.95 and 2.60 gm dose levels after NaSAM administration than after SAM. Mean total SAM concentration was significantly higher after NaSAM at all dosage levels. The sedative effects of salicylamide were assessed with a self-scoring questionnaire. Sedation seemed to increase with increasing dose of both NaSAM and SAM. The sedative response occurred earlier after NaSAM than after SAM. Side effects were minor and transient in nature, occurred at the higher dosage levels, and were predominantly lightheadedness and dizziness. Because NaSAM produces higher drug levels and has a more rapid onset of subjective effects, we conclude that it represents a potentially superior dosage form.", "contents": "Sodium salicylamide: relative bioavailability and subjective effects. The bioavailability of sodium salicylamide (NaSAM) in solution of salicylamide (SAM) tablets was compared in 6 healthy human volunteers. Bioavailability was assessed by plasma level determinations of nonmetabolized salicylamide (free SAM) and salicylamide plus conjugated metabolites (total SAM) for 3 hr following oral doses of 0.65, 1.30, 1.95, and 2.60 gm of salicylamide. The availability of NaSAM was found to be superior to SAM and dose-dependent. Mean peak levels of free SAM and total SAM were higher and were reached earlier after NaSAM liquid than after SAM tablets. Significantly higher mean levels of free SAM were found at the 1.95 and 2.60 gm dose levels after NaSAM administration than after SAM. Mean total SAM concentration was significantly higher after NaSAM at all dosage levels. The sedative effects of salicylamide were assessed with a self-scoring questionnaire. Sedation seemed to increase with increasing dose of both NaSAM and SAM. The sedative response occurred earlier after NaSAM than after SAM. Side effects were minor and transient in nature, occurred at the higher dosage levels, and were predominantly lightheadedness and dizziness. Because NaSAM produces higher drug levels and has a more rapid onset of subjective effects, we conclude that it represents a potentially superior dosage form."} {"id": "PMID:1269198", "title": "The effect of arterial oxygen tension on antipyrine half-time in plasma.", "content": "Hospital patients with depressed arterial oxygen tensions (PaO2) from pulmonary disease were given antipyrine orally or intravenously. The half-time (t1/2) of disappearance from plasma was measured. Other patients with normal PaO2 measurements were treated similarly. Patients whose PaO2 was 55 or below had longer t1/2 times than those of patients with a PaO2 above 55. This observation parallels that made previously in rats.", "contents": "The effect of arterial oxygen tension on antipyrine half-time in plasma. Hospital patients with depressed arterial oxygen tensions (PaO2) from pulmonary disease were given antipyrine orally or intravenously. The half-time (t1/2) of disappearance from plasma was measured. Other patients with normal PaO2 measurements were treated similarly. Patients whose PaO2 was 55 or below had longer t1/2 times than those of patients with a PaO2 above 55. This observation parallels that made previously in rats."} {"id": "PMID:1269202", "title": "Clinical trial methodology in intestinal parasitic diseases.", "content": "The high prevalence of intestinal parasitic infections as an index of underdevelopment, especially in tropical countries, is related to poverty, poor housing, lack of sanitation, malnutrition, and ignorance. The effects are lowered work capacity, physical and mental retardation, leading to recurrences and exacerbations of the parasitism and malnutrition. The most prevalent parasites, methods of detection by specific tests in patients in clinical trials involving antiparasitic drugs are dealt with. How and by whom investigations of new drugs should be undertaken, the need for a basic knowledge of parasitology and techniques of the discipline, of biostatistics, and use of such controls as randomized allotment to treatment groups, placebo administration, and double-blind assessments are emphasized. The justification for undertaking an evaluation of an antiparasitic drug is predicated on the demonstration of safety in exhaustive in vitro and animal studies and of the drug's potential superiority as to efficacy and lower incidence of unwanted side effects, as compared with existing agents. Tolerance and dose-range studies should be conducted in male adult hospitalized patients under close supervision. The evaluation of amebicides in clinical trials, as well as of anthelmintics, is considered in terms of differentiation and reproductive habits of specific causative agents and tests for detecting their elimination to determine improvement under drug therapy. The problem of reinfection, particuarly of nonhospitalized patients under the adverse conditions of life, is stressed.", "contents": "Clinical trial methodology in intestinal parasitic diseases. The high prevalence of intestinal parasitic infections as an index of underdevelopment, especially in tropical countries, is related to poverty, poor housing, lack of sanitation, malnutrition, and ignorance. The effects are lowered work capacity, physical and mental retardation, leading to recurrences and exacerbations of the parasitism and malnutrition. The most prevalent parasites, methods of detection by specific tests in patients in clinical trials involving antiparasitic drugs are dealt with. How and by whom investigations of new drugs should be undertaken, the need for a basic knowledge of parasitology and techniques of the discipline, of biostatistics, and use of such controls as randomized allotment to treatment groups, placebo administration, and double-blind assessments are emphasized. The justification for undertaking an evaluation of an antiparasitic drug is predicated on the demonstration of safety in exhaustive in vitro and animal studies and of the drug's potential superiority as to efficacy and lower incidence of unwanted side effects, as compared with existing agents. Tolerance and dose-range studies should be conducted in male adult hospitalized patients under close supervision. The evaluation of amebicides in clinical trials, as well as of anthelmintics, is considered in terms of differentiation and reproductive habits of specific causative agents and tests for detecting their elimination to determine improvement under drug therapy. The problem of reinfection, particuarly of nonhospitalized patients under the adverse conditions of life, is stressed."} {"id": "PMID:1269203", "title": "Sources of information on drug usage in Sweden.", "content": "Based on sales statistics, prescription habits and figures, interviews, and, in certain instances, on determinations of drug plasma levels, various aspects of drug usage in Sweden are examined. The working of the drug regulatory agency in Sweden is elucidated against the background of the above sources from which drug usage information is obtained.", "contents": "Sources of information on drug usage in Sweden. Based on sales statistics, prescription habits and figures, interviews, and, in certain instances, on determinations of drug plasma levels, various aspects of drug usage in Sweden are examined. The working of the drug regulatory agency in Sweden is elucidated against the background of the above sources from which drug usage information is obtained."} {"id": "PMID:1269204", "title": "The background pattern of drug usage in Australia.", "content": "The pattern of drug usage by urban populations has been studied in two typical Australian cities: Traralgon, Victoria, and Sydney, New South Wales. The study, lasting 1 year, involved questioning of 10% of the residents in households selected by random sampling and records of pharmacists. The questions related to state of health, recurrent or chronic disability, and drug exposures during 2 wk preceding the interview. Figures obtained from the Pharmaceutical Benefit Scheme (a system of partial federal subsidy) and the Morbidity Survey of the Royal Australasian College of General Practitioners showed Australians to be near the top of the world's drug takers, in comparison for example with Americans: between 6 and 7 prescriptions per capita in Australia and between 4 and 5 prescriptions in the United States in 1973. The consumption of over-the-counter drugs (OTC) was estimated from the Commonwealth Statistician's figures by subtracting the expenditure for prescription drugs from the total annual chemist sales--$A450,000,000. This represents a cost of $A33.85 for every man, woman, and child. Of this amount $A19.07 was spent for OTC drugs, analgesics and cough suppressants being the two largest items. Roughly 60% of Australians average two or more doses of analgesics per day, with some patients consuming 12 or more doses a day. An association between this high consumption of analgesics and an alarming incidence of iatrogenic disease--analgesic nephropathy and gastrointestinal hemorrhage--is postulated. It is concluded that this level of drug usage must be symptomatic of underlying stresses and pressures of urban society in that country, along with a cultural factor of ready acceptance of the social use of drugs.", "contents": "The background pattern of drug usage in Australia. The pattern of drug usage by urban populations has been studied in two typical Australian cities: Traralgon, Victoria, and Sydney, New South Wales. The study, lasting 1 year, involved questioning of 10% of the residents in households selected by random sampling and records of pharmacists. The questions related to state of health, recurrent or chronic disability, and drug exposures during 2 wk preceding the interview. Figures obtained from the Pharmaceutical Benefit Scheme (a system of partial federal subsidy) and the Morbidity Survey of the Royal Australasian College of General Practitioners showed Australians to be near the top of the world's drug takers, in comparison for example with Americans: between 6 and 7 prescriptions per capita in Australia and between 4 and 5 prescriptions in the United States in 1973. The consumption of over-the-counter drugs (OTC) was estimated from the Commonwealth Statistician's figures by subtracting the expenditure for prescription drugs from the total annual chemist sales--$A450,000,000. This represents a cost of $A33.85 for every man, woman, and child. Of this amount $A19.07 was spent for OTC drugs, analgesics and cough suppressants being the two largest items. Roughly 60% of Australians average two or more doses of analgesics per day, with some patients consuming 12 or more doses a day. An association between this high consumption of analgesics and an alarming incidence of iatrogenic disease--analgesic nephropathy and gastrointestinal hemorrhage--is postulated. It is concluded that this level of drug usage must be symptomatic of underlying stresses and pressures of urban society in that country, along with a cultural factor of ready acceptance of the social use of drugs."} {"id": "PMID:1269205", "title": "Patterns and problems of drug consumption in a developing country.", "content": "Delayed and sometimes total lack of communications, lower standards of medical care, low physician: population ratio, absence of monitoring systems affect all phases of drug consumption in developing countries--from procedures for introducing a new drug to its marketing on a broad scale, and ultimate decline. The number of prescriptions and the choice of drug are determined only partly by physicians. Such other factors as medicaments furnished by the government either free or at a small charge, the type of health service, accessibility to paramedical and nonmedical advice, as well as hard-sell marketing practices, often through the mass media, tend to set the pattern of drug usage. The practice of drug storming in \"home pharmacies\", a phenomenon surveyed by the author, is described and the reasons for it analyzed. In general, the categories of drugs (e.g., antibiotics, cardiovascular, analgesics) consumed are the same in the rest of Europe, the United States, and Latin America. Among the minor tranquilizers, the consumption of meprobamate has risen by about a third, chlordiazepoxide markedly, while phenobarbital consumption has remained about the same from 1969 to 1973. This is said to illustrate the pattern of an upward curve in consumption of a new drug, and the displacement of an old one. The overall rise of these drugs during this period was 72.1% in Hungary. Similar surveys are reported for oral hypoglycemic and antiarrhythmic drugs. Of hypotensive drugs, rauwolfia usage has declined and methyldopa has increased by over 200%.", "contents": "Patterns and problems of drug consumption in a developing country. Delayed and sometimes total lack of communications, lower standards of medical care, low physician: population ratio, absence of monitoring systems affect all phases of drug consumption in developing countries--from procedures for introducing a new drug to its marketing on a broad scale, and ultimate decline. The number of prescriptions and the choice of drug are determined only partly by physicians. Such other factors as medicaments furnished by the government either free or at a small charge, the type of health service, accessibility to paramedical and nonmedical advice, as well as hard-sell marketing practices, often through the mass media, tend to set the pattern of drug usage. The practice of drug storming in \"home pharmacies\", a phenomenon surveyed by the author, is described and the reasons for it analyzed. In general, the categories of drugs (e.g., antibiotics, cardiovascular, analgesics) consumed are the same in the rest of Europe, the United States, and Latin America. Among the minor tranquilizers, the consumption of meprobamate has risen by about a third, chlordiazepoxide markedly, while phenobarbital consumption has remained about the same from 1969 to 1973. This is said to illustrate the pattern of an upward curve in consumption of a new drug, and the displacement of an old one. The overall rise of these drugs during this period was 72.1% in Hungary. Similar surveys are reported for oral hypoglycemic and antiarrhythmic drugs. Of hypotensive drugs, rauwolfia usage has declined and methyldopa has increased by over 200%."} {"id": "PMID:1269206", "title": "Culture, morbidity, and the effects of drugs.", "content": "In the evaluation of drug efficacy, despite the customary device of randomization, regional differences of prevalence of a given disease, unique culturally determined practices in treatment, and differential tolerances to side effects are complicating factors in transcultural pharmacology that must be taken into account in the interpretation of efficacy and toxicity. This thesis is documented by illustrations from psychiatric practice, e.g., prevalence and morbidity of alcoholism, cultural differences as to prevalence, diagnosis, and symptomatology of schizophrenia, even to the point of widely discrepant diagnosis of a given patient, depending upon whether the examination was done by an American or British psychiatrist. Similar differences concerning the existence of disease entities other than psychiatric are cited, e.g., hepatic insufficiently considered common in some Latin populations; low blood pressure a recognized and treatable condition in Eastern Europe. The incidence of side effects from the same drug may also vary in different cultures, making the interpretation of their significance difficult, and cross-cultural comparisons hazardous. To avoid some of these pitfalls, it is essential to recognize (1) the many complexities inherent in trials involving differing cultures and (2) to design the studies insofar as possible to include measurement of population variables.", "contents": "Culture, morbidity, and the effects of drugs. In the evaluation of drug efficacy, despite the customary device of randomization, regional differences of prevalence of a given disease, unique culturally determined practices in treatment, and differential tolerances to side effects are complicating factors in transcultural pharmacology that must be taken into account in the interpretation of efficacy and toxicity. This thesis is documented by illustrations from psychiatric practice, e.g., prevalence and morbidity of alcoholism, cultural differences as to prevalence, diagnosis, and symptomatology of schizophrenia, even to the point of widely discrepant diagnosis of a given patient, depending upon whether the examination was done by an American or British psychiatrist. Similar differences concerning the existence of disease entities other than psychiatric are cited, e.g., hepatic insufficiently considered common in some Latin populations; low blood pressure a recognized and treatable condition in Eastern Europe. The incidence of side effects from the same drug may also vary in different cultures, making the interpretation of their significance difficult, and cross-cultural comparisons hazardous. To avoid some of these pitfalls, it is essential to recognize (1) the many complexities inherent in trials involving differing cultures and (2) to design the studies insofar as possible to include measurement of population variables."} {"id": "PMID:1269207", "title": "Variations in disease prevalence in the Americas.", "content": "Data are presented from North American and Latin American countries of the leading causes of death and death rates, demonstrating the sharp differences based on social and economic development of these respective countries. Whereas ischemic heart disease and malignant neoplasms head the list of deaths in the United States and Canada, infective and parasitic diseases of the gut, with diarrhea very common, are the principal causes of death in Latin America. Nutritional deficiency, the most important contributory cause associated with infections and diarrhea, accounts for the very high infant mortality rate in the latter countries. These pathologic conditions have a direct relationship to the degree of social and economic level of development in Latin America, and constitute a complex public health problem of enormous proportions.", "contents": "Variations in disease prevalence in the Americas. Data are presented from North American and Latin American countries of the leading causes of death and death rates, demonstrating the sharp differences based on social and economic development of these respective countries. Whereas ischemic heart disease and malignant neoplasms head the list of deaths in the United States and Canada, infective and parasitic diseases of the gut, with diarrhea very common, are the principal causes of death in Latin America. Nutritional deficiency, the most important contributory cause associated with infections and diarrhea, accounts for the very high infant mortality rate in the latter countries. These pathologic conditions have a direct relationship to the degree of social and economic level of development in Latin America, and constitute a complex public health problem of enormous proportions."} {"id": "PMID:1269208", "title": "How study of geographic epidemiology of disease can help in detection of adverse drug reactions.", "content": "The geographic epidemiology of adverse drug reactions can often help in their recognition and in pinpointing the responsible drug. Since different countries often introduce new drugs at varying periods of time and they achieve varying degrees of popularity and use, this information may sometimes aid the epidemiologist in the search for the etiology of unwanted drug effects. Some examples where geography helped unravel the story behind certain adverse drug reactions are presented.", "contents": "How study of geographic epidemiology of disease can help in detection of adverse drug reactions. The geographic epidemiology of adverse drug reactions can often help in their recognition and in pinpointing the responsible drug. Since different countries often introduce new drugs at varying periods of time and they achieve varying degrees of popularity and use, this information may sometimes aid the epidemiologist in the search for the etiology of unwanted drug effects. Some examples where geography helped unravel the story behind certain adverse drug reactions are presented."} {"id": "PMID:1269209", "title": "Drug regulation in the United Kingdom.", "content": "The British system under the Medicines Act by which new drug applications are evaluated is described in a step-by-step manner from submission of application to the issuance of a clinical trial certificate by the licensing authority. At the end of a period by clinical trials the submission is brought back for a product license. Once a drug is marketed it falls within the purview of the adverse reaction monitoring group of the Committee on Safety of Medicines (CSM). A recent innovation is \"monitored release\", by which, for a period of time after marketing, case reports are submitted by the pharmaceutical company to the CSM. The advantages of the British system are: (1) the final licensing decisions being made by the academic members of the Committee means that they are insulated from commercial and political pressures, and are additionally reached without undue delay; (2) academic members are not permitted to be retained as consultants to the industry on a long-term basis; (3) evaluation solely on British studies is not obligatory--foreign studies are also acceptable. Weakness in the system are: (1) recruitment of people experienced in pharmacology and therapeutics is difficult; (2) there is an inordinate work load on the academic members of the Main Committee and Subcommittees. Importance of an effective monitoring in the postmarketing stage is emphasized, because the long-term judgement must necessarily be based on wide experience in the field. The multiplication of the same of similar drugs is deplored, and innovative efforts in the quest for new drugs, especially for rare diseases, are to be encouraged.", "contents": "Drug regulation in the United Kingdom. The British system under the Medicines Act by which new drug applications are evaluated is described in a step-by-step manner from submission of application to the issuance of a clinical trial certificate by the licensing authority. At the end of a period by clinical trials the submission is brought back for a product license. Once a drug is marketed it falls within the purview of the adverse reaction monitoring group of the Committee on Safety of Medicines (CSM). A recent innovation is \"monitored release\", by which, for a period of time after marketing, case reports are submitted by the pharmaceutical company to the CSM. The advantages of the British system are: (1) the final licensing decisions being made by the academic members of the Committee means that they are insulated from commercial and political pressures, and are additionally reached without undue delay; (2) academic members are not permitted to be retained as consultants to the industry on a long-term basis; (3) evaluation solely on British studies is not obligatory--foreign studies are also acceptable. Weakness in the system are: (1) recruitment of people experienced in pharmacology and therapeutics is difficult; (2) there is an inordinate work load on the academic members of the Main Committee and Subcommittees. Importance of an effective monitoring in the postmarketing stage is emphasized, because the long-term judgement must necessarily be based on wide experience in the field. The multiplication of the same of similar drugs is deplored, and innovative efforts in the quest for new drugs, especially for rare diseases, are to be encouraged."} {"id": "PMID:1269210", "title": "Regulatory differences and similarities: systems in Japan.", "content": "The historic steps that led up to the present federal drug regulations in the United States are outlined as a background to the development of the current drug regulatory system in Japan, consisting of the procedures for approval of new drugs, of double-brand naming, by which the same drug under different names can be sold as ethical or over-the-counter (OTC). The more recent provisions for re-evaluation of drugs, the mechanism for monitoring adverse reactions, and the dissemination of the collected information are described. The prescription habits of physicians, the influence of the health insurance systems on these, and the strikingly high level of drug consumption in Japan, as compared with those in other industrial countries, are discussed and illustrated graphically.", "contents": "Regulatory differences and similarities: systems in Japan. The historic steps that led up to the present federal drug regulations in the United States are outlined as a background to the development of the current drug regulatory system in Japan, consisting of the procedures for approval of new drugs, of double-brand naming, by which the same drug under different names can be sold as ethical or over-the-counter (OTC). The more recent provisions for re-evaluation of drugs, the mechanism for monitoring adverse reactions, and the dissemination of the collected information are described. The prescription habits of physicians, the influence of the health insurance systems on these, and the strikingly high level of drug consumption in Japan, as compared with those in other industrial countries, are discussed and illustrated graphically."} {"id": "PMID:1269213", "title": "Drug evaluation, educational system, and clinical pharmacologic training in a small country.", "content": "The need for clinical pharmacology as an integral part of medical training is emphasized. The lack of a formal system of educating candidates in this discipline in a small country with limited means of personnel and funds has to be compensated for by close cooperation among practicing physicians, clinical pharmacologists in universities and some hospitals, industry technologists, and the personnel serving on national drug regulation committees. The system of drug regulation in Denmark and its tangential contribution to educating the younger clinical pharmacologists are described. The efficiency as well as the limitations of the system are assessed.", "contents": "Drug evaluation, educational system, and clinical pharmacologic training in a small country. The need for clinical pharmacology as an integral part of medical training is emphasized. The lack of a formal system of educating candidates in this discipline in a small country with limited means of personnel and funds has to be compensated for by close cooperation among practicing physicians, clinical pharmacologists in universities and some hospitals, industry technologists, and the personnel serving on national drug regulation committees. The system of drug regulation in Denmark and its tangential contribution to educating the younger clinical pharmacologists are described. The efficiency as well as the limitations of the system are assessed."} {"id": "PMID:1269214", "title": "A completely absorbed oral preparation of digoxin.", "content": "Digoxin absorption was studied in healthy volunteers by determination of peak plasma concentrations, areas under plasma concentration curves, and urinary excretion after single-dose administration. By comparison with an aqueous solution, increased rate and extent of absorption occurred from experimental soft gelatin formulations of digoxin in solution. Enhanced bioavailability of the capsules was not affected by altered volume of contained solvent. Digoxin was considerably better absorbed from capsules than from tablets of moderately high dissolution rate. Mean percentage intestinal absorption was 75% from tablet and 97% from capsules. Reduced between-subject variability accompanied the enhanced absorption from capsules.", "contents": "A completely absorbed oral preparation of digoxin. Digoxin absorption was studied in healthy volunteers by determination of peak plasma concentrations, areas under plasma concentration curves, and urinary excretion after single-dose administration. By comparison with an aqueous solution, increased rate and extent of absorption occurred from experimental soft gelatin formulations of digoxin in solution. Enhanced bioavailability of the capsules was not affected by altered volume of contained solvent. Digoxin was considerably better absorbed from capsules than from tablets of moderately high dissolution rate. Mean percentage intestinal absorption was 75% from tablet and 97% from capsules. Reduced between-subject variability accompanied the enhanced absorption from capsules."} {"id": "PMID:1269215", "title": "Kinetics of high-dose intravenous morphine in cardiac surgery patients.", "content": "Ten patients received 1.0 mg/kg of morphine sulfate by constant-rate intravenous infusion at 5 mg/min over 9 to 27 min. Multiple arterial blood samples were drawn during the first 30 to 151 min after termination of the infusion, prior to institution of cardiopulmonary bypass. Postinfusion plasma concentrations were fitted by computer to biexponential functions consistent with a 2-compartment open pharmacokinetic model. Mean (+/- SE) pharmacokinetic parameters were: volume of central compartment, 0.09 +/- 0.03 L/kg; total apparent volume of distribution, 1.02 +/- 0.09 L/kg; distribution T 1/2, 0.90 +/- 0.09 min; apparent elimination T 1/2, 137 +/- 14 min; total clearance, 378 +/- 63 ml/min. Thus distribution of morphine is very rapid, but the apparent volume of distribution is only slightly larger than body weight, suggesting limited tissue uptake. Since apparent elimination T 1/2s are similar to those reported after smaller doses, evidence of saturable or capacity-linked elimination is lacking. Total clearances, representing mainly hepatic clearance, averaged about 25% of hepatic blood flow, suggesting clinically important first-pass metabolism of oral morphine.", "contents": "Kinetics of high-dose intravenous morphine in cardiac surgery patients. Ten patients received 1.0 mg/kg of morphine sulfate by constant-rate intravenous infusion at 5 mg/min over 9 to 27 min. Multiple arterial blood samples were drawn during the first 30 to 151 min after termination of the infusion, prior to institution of cardiopulmonary bypass. Postinfusion plasma concentrations were fitted by computer to biexponential functions consistent with a 2-compartment open pharmacokinetic model. Mean (+/- SE) pharmacokinetic parameters were: volume of central compartment, 0.09 +/- 0.03 L/kg; total apparent volume of distribution, 1.02 +/- 0.09 L/kg; distribution T 1/2, 0.90 +/- 0.09 min; apparent elimination T 1/2, 137 +/- 14 min; total clearance, 378 +/- 63 ml/min. Thus distribution of morphine is very rapid, but the apparent volume of distribution is only slightly larger than body weight, suggesting limited tissue uptake. Since apparent elimination T 1/2s are similar to those reported after smaller doses, evidence of saturable or capacity-linked elimination is lacking. Total clearances, representing mainly hepatic clearance, averaged about 25% of hepatic blood flow, suggesting clinically important first-pass metabolism of oral morphine."} {"id": "PMID:1269216", "title": "Kinetics of the oral antiarrhythmic lidocaine congener, tocainide.", "content": "Tocainide, a primary amine analogue of lidocaine, is effective against some experimental and clinical arrhythmias. Its pharmacokinetic behavior was studied in 6 healthy male subjects. Peak blood levels (CB max) and area under the blood concentration-time curve (AUC) were linearly related to dose with slopes of 0.0067 mcg/ml and 6 min mcg/ml per milligram of dose, respectively. Renal clearance of tocainide averaged 59 ml/min when urinary pH was uncontrolled or acidified, while it was reduced to 13 ml/min during intense sodium bicarbonate loading. Blood levels following intravenous infusion were well described by a 2-compartment open model with a volume of the central compartment of 0.92 L/kg. The t 1/2 beta was 11 hr and total body clearance was 166 ml/min. Loo-Riegelman analysis of the absorption rate did not allow unequivocal assignment of an \"order\" to the absorption process. Bioavailability approached 100%. Administration of drug 5 min after a test meal suppressed CB max 40% but minimally affected AUC. Approximately 50% of the drug was found to be plasma protein bound at clinically effective concentrations.", "contents": "Kinetics of the oral antiarrhythmic lidocaine congener, tocainide. Tocainide, a primary amine analogue of lidocaine, is effective against some experimental and clinical arrhythmias. Its pharmacokinetic behavior was studied in 6 healthy male subjects. Peak blood levels (CB max) and area under the blood concentration-time curve (AUC) were linearly related to dose with slopes of 0.0067 mcg/ml and 6 min mcg/ml per milligram of dose, respectively. Renal clearance of tocainide averaged 59 ml/min when urinary pH was uncontrolled or acidified, while it was reduced to 13 ml/min during intense sodium bicarbonate loading. Blood levels following intravenous infusion were well described by a 2-compartment open model with a volume of the central compartment of 0.92 L/kg. The t 1/2 beta was 11 hr and total body clearance was 166 ml/min. Loo-Riegelman analysis of the absorption rate did not allow unequivocal assignment of an \"order\" to the absorption process. Bioavailability approached 100%. Administration of drug 5 min after a test meal suppressed CB max 40% but minimally affected AUC. Approximately 50% of the drug was found to be plasma protein bound at clinically effective concentrations."} {"id": "PMID:1269217", "title": "Effects of dextroamphetamine on psychomotor skills.", "content": "Twelve healthy male volunteers were given 0, 5, 10, 15 mg/70 kg dextroamphetamine orally in a randomized double-blind fashion. Blood pressure increased linearly with dose while heart rate was unchanged. Although selected individual tests of stance stability and motor function improved in a dose-related fashion, a generalized improvement in performance was not found. Delayed Auditory Feedback (DAF) failed to show improvement in mental performance after dextroamphetamine.", "contents": "Effects of dextroamphetamine on psychomotor skills. Twelve healthy male volunteers were given 0, 5, 10, 15 mg/70 kg dextroamphetamine orally in a randomized double-blind fashion. Blood pressure increased linearly with dose while heart rate was unchanged. Although selected individual tests of stance stability and motor function improved in a dose-related fashion, a generalized improvement in performance was not found. Delayed Auditory Feedback (DAF) failed to show improvement in mental performance after dextroamphetamine."} {"id": "PMID:1269218", "title": "Absorption of pyrvinium pamoate.", "content": "Pyrvinium pamoate, tablets and suspension, was administered as single 350-mg doses to 12 healthy male volunteers to determine whether there had been any systemic absorption. Six subjects received tablets and 6 received suspension on the first day; on day 8, subjects received the other dose form. Up to 4 days after administration there was no evidence of drug in blood and urine by spectroflorometric assay. Metabolic studies in rats showed minute quantities of drug in the liver and plasma but not of any metabolites.", "contents": "Absorption of pyrvinium pamoate. Pyrvinium pamoate, tablets and suspension, was administered as single 350-mg doses to 12 healthy male volunteers to determine whether there had been any systemic absorption. Six subjects received tablets and 6 received suspension on the first day; on day 8, subjects received the other dose form. Up to 4 days after administration there was no evidence of drug in blood and urine by spectroflorometric assay. Metabolic studies in rats showed minute quantities of drug in the liver and plasma but not of any metabolites."} {"id": "PMID:1269219", "title": "Plasma concentration of edrophonium in man.", "content": "The plasma concentration of edrophonium was measured in man after intravenous administration. In 5 patients, the clearance of edrophonium from the circulation during the 1-hr period of sampling was invariably resolved into 2 exponential components. An initial rapid phase of elimination from plasma (T/2 = 0.54 TO 1.92 Min) was followed by a much slower decline (T/2 = 24.23 to 45.00 Min), corresponding to the fall in concentration between 10 and 60 min. In parallel experiments in the rat, the clearance of 14C-edrophonium was resolved into 3 exponential components, although the final component could not be reliably defined until 1 to 3 hr after intravenous injection. It is suggested that the rapid fall in the plasma concentration of edrophonium in both species is not dependent on metabolism or excretion, but is due to the rapid uptake of the drug by the liver and kidneys.", "contents": "Plasma concentration of edrophonium in man. The plasma concentration of edrophonium was measured in man after intravenous administration. In 5 patients, the clearance of edrophonium from the circulation during the 1-hr period of sampling was invariably resolved into 2 exponential components. An initial rapid phase of elimination from plasma (T/2 = 0.54 TO 1.92 Min) was followed by a much slower decline (T/2 = 24.23 to 45.00 Min), corresponding to the fall in concentration between 10 and 60 min. In parallel experiments in the rat, the clearance of 14C-edrophonium was resolved into 3 exponential components, although the final component could not be reliably defined until 1 to 3 hr after intravenous injection. It is suggested that the rapid fall in the plasma concentration of edrophonium in both species is not dependent on metabolism or excretion, but is due to the rapid uptake of the drug by the liver and kidneys."} {"id": "PMID:1269257", "title": "PATER: a program for parenthood diagnosis.", "content": "Spectacular progress has been made within the last 20 years in the knowledge of the human polymorphism. These data, observed on a father-mother-child triplet provides aid to the decision for the parenthood diagnosis for either the purpose of forensic medicine as the validation of data files in genetic research. This work gives an algorithm of parenthood diagnosis which achieve logical verifications and various calculating while occupying very little place in central memory. We propose a tool for decision-making, the exclusion percentage and we determine the most efficient sequence having the least cost to use these systems sequentially and to stop the verification by a given decision threshold.", "contents": "PATER: a program for parenthood diagnosis. Spectacular progress has been made within the last 20 years in the knowledge of the human polymorphism. These data, observed on a father-mother-child triplet provides aid to the decision for the parenthood diagnosis for either the purpose of forensic medicine as the validation of data files in genetic research. This work gives an algorithm of parenthood diagnosis which achieve logical verifications and various calculating while occupying very little place in central memory. We propose a tool for decision-making, the exclusion percentage and we determine the most efficient sequence having the least cost to use these systems sequentially and to stop the verification by a given decision threshold."} {"id": "PMID:1269258", "title": "An off-line data processing system for biochemistry profiling based on a 2K programmable calculator.", "content": "An off-line data processing system based on a Hewlett Packard 2K programmable calculator to be used with a biochemistry profiling system is described. The program is in two sections. A Data Acquisition phase calculates results from Auto Analyser II peak heights after corrections for drift and stores them on magnetic tape cassettes. Quality control statistics are produced. A Reporting phase types the profile results on self-adhesive pre-printed labels to be attached to the test-request form and also prepares a laboratory record sheet. The system is routinely used to process up to 2000 peak heights per day. Non-profile heights may also be read using this program.", "contents": "An off-line data processing system for biochemistry profiling based on a 2K programmable calculator. An off-line data processing system based on a Hewlett Packard 2K programmable calculator to be used with a biochemistry profiling system is described. The program is in two sections. A Data Acquisition phase calculates results from Auto Analyser II peak heights after corrections for drift and stores them on magnetic tape cassettes. Quality control statistics are produced. A Reporting phase types the profile results on self-adhesive pre-printed labels to be attached to the test-request form and also prepares a laboratory record sheet. The system is routinely used to process up to 2000 peak heights per day. Non-profile heights may also be read using this program."} {"id": "PMID:1269259", "title": "On-line computer processing of pressure data from cardiac catheterizations.", "content": "A flexible program system for on-line analysis of pressure data from cardiac catheterizations is described. The programs are implemented on an IBM 1800 computer, equipped with remote oscilloscope/keyboard terminals. The current computer system can handle any combination of up to 4 pressure signals. During catheterization, measurement specifications (i.e. calibration levels or sites of pressure recordings) are entered via the keyboard immediately before each recording. As an option the whole expected measurement sequence may be stored on disk before the catheterization starts. This method will minimize the necessary interaction with the computer when the same catheterization procedure is used on several occasions. Changes from the predetermined scheme may, however, be undertaken before each recording to meet with unexpected events that may arise during the catheterization. After computer detection of calibration levels, the recorded signals are digitized during 20 seconds and analysed beat-by-beat. Calculated values are averaged and presented on the terminal oscilloscope in tabular and/or graphic form. The waveform analysis performed by the program system is validated in a statistical comparison between manually and automatically computed values.", "contents": "On-line computer processing of pressure data from cardiac catheterizations. A flexible program system for on-line analysis of pressure data from cardiac catheterizations is described. The programs are implemented on an IBM 1800 computer, equipped with remote oscilloscope/keyboard terminals. The current computer system can handle any combination of up to 4 pressure signals. During catheterization, measurement specifications (i.e. calibration levels or sites of pressure recordings) are entered via the keyboard immediately before each recording. As an option the whole expected measurement sequence may be stored on disk before the catheterization starts. This method will minimize the necessary interaction with the computer when the same catheterization procedure is used on several occasions. Changes from the predetermined scheme may, however, be undertaken before each recording to meet with unexpected events that may arise during the catheterization. After computer detection of calibration levels, the recorded signals are digitized during 20 seconds and analysed beat-by-beat. Calculated values are averaged and presented on the terminal oscilloscope in tabular and/or graphic form. The waveform analysis performed by the program system is validated in a statistical comparison between manually and automatically computed values."} {"id": "PMID:1269260", "title": "A computer program suitable for fitting linear models when the dependent variable is dichotomous, polichotomous or censored survival and non-linear models when the dependent variable is quantitative.", "content": "Given a set of measurements of s explanatory variables corresponding to each experimental unit, a computer program, whose methodological background can be found in [2] has been written in FORTRAN IV language in order to perform regression analyses when the dependent variable is: (i) dichotomous; (ii) polichotomous; (iii) censored survival. In the two former the Cox's [6] linear logistic models are used while in the third one it has been resorted to the models suggested by Feigl and Zelen [8]. The statistical estimation procedure is maximum likelihood and among the different algorithms developed to reach this goal, the one published by Van der Voort and Dorpema [3], has been utilized. Furthermore, when the dependent variable is quantitative, the program is suitable to fit any function non-linear in the parameters; the pertinent function and its first and second derivatives must be provided by the user. In the present version, implemented on a Univac 1106 machine, the program fits directly the Gompertz function.", "contents": "A computer program suitable for fitting linear models when the dependent variable is dichotomous, polichotomous or censored survival and non-linear models when the dependent variable is quantitative. Given a set of measurements of s explanatory variables corresponding to each experimental unit, a computer program, whose methodological background can be found in [2] has been written in FORTRAN IV language in order to perform regression analyses when the dependent variable is: (i) dichotomous; (ii) polichotomous; (iii) censored survival. In the two former the Cox's [6] linear logistic models are used while in the third one it has been resorted to the models suggested by Feigl and Zelen [8]. The statistical estimation procedure is maximum likelihood and among the different algorithms developed to reach this goal, the one published by Van der Voort and Dorpema [3], has been utilized. Furthermore, when the dependent variable is quantitative, the program is suitable to fit any function non-linear in the parameters; the pertinent function and its first and second derivatives must be provided by the user. In the present version, implemented on a Univac 1106 machine, the program fits directly the Gompertz function."} {"id": "PMID:1269261", "title": "An automated laboratory control system: collection and analysis of behavioral and electro-physiological data.", "content": "A system of man-machine interactive PDP-11 assembly language programs is described which presents stimuli to a subject and records and analyzes behavioral and evoked potential data. The system was designed for researchers with no knowledge of computer programming and enables the user to create complicated sequences of stimulus presentations (\"trials\") and sequences of successive trials (\"runs\"), with no new programming required. The system is written for DEC.s DECLAB 11/40 system.", "contents": "An automated laboratory control system: collection and analysis of behavioral and electro-physiological data. A system of man-machine interactive PDP-11 assembly language programs is described which presents stimuli to a subject and records and analyzes behavioral and evoked potential data. The system was designed for researchers with no knowledge of computer programming and enables the user to create complicated sequences of stimulus presentations (\"trials\") and sequences of successive trials (\"runs\"), with no new programming required. The system is written for DEC.s DECLAB 11/40 system."} {"id": "PMID:1269265", "title": "Quantitative radiocardiography in major pulmonary thromboembolism.", "content": "Cardiac index (CI) and pulmonary blood volume index (PVBI) were measured by quantitative radiocardiographic studies using radioactive 113mindium and a scintillation probe in 37 patients with confirmed major pulmonary thromboembolism. The mean PBVI was 185 +/- 11 ml/sq m (SE) and was significantly less than normal (310 +/- 5 ml/sq m [SE]; P less than 0.001). Six patients with major pulmonary thromboembilism had a PBVI within the normal range (262 to 358 ml/sq m; mean +/- 2 SD), and the mean pulmonary vascular occlusion was 21 percent in these patients. Eighteen patients (49 percent) died, and the most significant correlate of mortality was CI, which was depressed (less than 2.7 L/min/sq m) in all but two. Twenty-three serial determinations of pulmonary blood volume (PBV) ranging from 1 to 18 days after the initial study showed a mean increase in PBV of 27 ml/day in ten survivors. Quantitative radiocardiographic studies provide a means of diagnosing major pulmonary thromboembolism by measuring decreases in PBVI; it can assess the magnitude of major pulmonary thromboembolism and can assess CI and, thereby, predict risk of mortality; and it provides a means of following the resolution rate of major pulmonary thromboembolism.", "contents": "Quantitative radiocardiography in major pulmonary thromboembolism. Cardiac index (CI) and pulmonary blood volume index (PVBI) were measured by quantitative radiocardiographic studies using radioactive 113mindium and a scintillation probe in 37 patients with confirmed major pulmonary thromboembolism. The mean PBVI was 185 +/- 11 ml/sq m (SE) and was significantly less than normal (310 +/- 5 ml/sq m [SE]; P less than 0.001). Six patients with major pulmonary thromboembilism had a PBVI within the normal range (262 to 358 ml/sq m; mean +/- 2 SD), and the mean pulmonary vascular occlusion was 21 percent in these patients. Eighteen patients (49 percent) died, and the most significant correlate of mortality was CI, which was depressed (less than 2.7 L/min/sq m) in all but two. Twenty-three serial determinations of pulmonary blood volume (PBV) ranging from 1 to 18 days after the initial study showed a mean increase in PBV of 27 ml/day in ten survivors. Quantitative radiocardiographic studies provide a means of diagnosing major pulmonary thromboembolism by measuring decreases in PBVI; it can assess the magnitude of major pulmonary thromboembolism and can assess CI and, thereby, predict risk of mortality; and it provides a means of following the resolution rate of major pulmonary thromboembolism."} {"id": "PMID:1269266", "title": "Radionuclidic lung-imaging procedures in the assessment of injury due to ammonia inhalation.", "content": "Clinical, physiologic, and bronchoscopic findings in a young man with acute injury of the respiratory tract due to inhalation of ammonia are described. Six months later, the patient's pulmonary function was reassessed by three radionuclidic lung-imaging procedures, which first revealed the sites and extent of the persisting obstructive disease processes. The diagnostic accuracy of the initial findings with radioactive xenon and aerosol were verified by the results of repeated bronchoscopic examination, bronchographic studies, standard pulmonary function tests, and lung-imaging procedures.", "contents": "Radionuclidic lung-imaging procedures in the assessment of injury due to ammonia inhalation. Clinical, physiologic, and bronchoscopic findings in a young man with acute injury of the respiratory tract due to inhalation of ammonia are described. Six months later, the patient's pulmonary function was reassessed by three radionuclidic lung-imaging procedures, which first revealed the sites and extent of the persisting obstructive disease processes. The diagnostic accuracy of the initial findings with radioactive xenon and aerosol were verified by the results of repeated bronchoscopic examination, bronchographic studies, standard pulmonary function tests, and lung-imaging procedures."} {"id": "PMID:1269267", "title": "Heart block complicating acute inferior wall myocardial infarction.", "content": "Heart block was noted in 60 (35 complete and 25 second-degree) of 410 patients with acute inferior wall myocardial infarction. This group with heart block was compared to a control group of 30 patients with acute inferior wall infarction without heart block. The incidences of prior myocardial infarction and hypertension, in addition to the highest level of serum creatine phosphokinase and a maximum degree of ST-segment elevation in the inferior leads, were all greater in patients with heart block, as compared to the controls. The incidences of various complications, including dizziness and syncope, transient hypotension, cardiogenic shock, and congestive heart failure, were also higher in the group with heart block, while sinus nodal distrubances and atrial arrhythmias occurred with equal frequency. The mortality in those with heart block was 28 percent compared to 13 percent for the control. It is concluded that patients with heart block complicating acute inferior myocardial infarction have a greater amount of myocardial necrosis, a higher incidence of complications, and a higher mortality. Insertion of a temporary pacemaker should be considered when specific indications are present and not routinely.", "contents": "Heart block complicating acute inferior wall myocardial infarction. Heart block was noted in 60 (35 complete and 25 second-degree) of 410 patients with acute inferior wall myocardial infarction. This group with heart block was compared to a control group of 30 patients with acute inferior wall infarction without heart block. The incidences of prior myocardial infarction and hypertension, in addition to the highest level of serum creatine phosphokinase and a maximum degree of ST-segment elevation in the inferior leads, were all greater in patients with heart block, as compared to the controls. The incidences of various complications, including dizziness and syncope, transient hypotension, cardiogenic shock, and congestive heart failure, were also higher in the group with heart block, while sinus nodal distrubances and atrial arrhythmias occurred with equal frequency. The mortality in those with heart block was 28 percent compared to 13 percent for the control. It is concluded that patients with heart block complicating acute inferior myocardial infarction have a greater amount of myocardial necrosis, a higher incidence of complications, and a higher mortality. Insertion of a temporary pacemaker should be considered when specific indications are present and not routinely."} {"id": "PMID:1269268", "title": "Lesions of conduction tissue complicating aortic valvular replacement.", "content": "A pathologic study of the cardiac conduction system was performed in 57 patients who died within 30 days after aortic valvular replacement. Histologically, there were old and recent lesions present in 34 (60 percent) and 43 (75 percent) of the patients, respectively. Old lesions did not show meaningful correlation with preoperative electrocardiograms. Although nontraumatic recent lesions were rarely the cause of postoperative abnormal cardiac conduction, traumatic lesions were frequently associated with loss of sinus mechanism. The main cause of trauma to the major cardiac conduction tissue was injury by sutures. The short membranous septum predisposed to injury, while the configuration of the left ventricular outflow tract was not a significant factor in injury. Traumatic lesions of the cardiac conduction tissue were more common in subjects with bicuspid than tricuspid aortic valves.", "contents": "Lesions of conduction tissue complicating aortic valvular replacement. A pathologic study of the cardiac conduction system was performed in 57 patients who died within 30 days after aortic valvular replacement. Histologically, there were old and recent lesions present in 34 (60 percent) and 43 (75 percent) of the patients, respectively. Old lesions did not show meaningful correlation with preoperative electrocardiograms. Although nontraumatic recent lesions were rarely the cause of postoperative abnormal cardiac conduction, traumatic lesions were frequently associated with loss of sinus mechanism. The main cause of trauma to the major cardiac conduction tissue was injury by sutures. The short membranous septum predisposed to injury, while the configuration of the left ventricular outflow tract was not a significant factor in injury. Traumatic lesions of the cardiac conduction tissue were more common in subjects with bicuspid than tricuspid aortic valves."} {"id": "PMID:1269269", "title": "Incidence and significance of pleural effusion after abdominal surgery.", "content": "Two hundred patients who had undergone abdominal surgery received bilateral decubitus chest roentgenograms between 48 and 72 hours after surgery to evaluate the incidence of pleural effusion after abdominal surgery. Ninety-seven (49 percent) had some pleural fluid visible on the x-ray films. In 50 patients the thickness of the fluid was less than 4 mm on the decubitus film; in 26, it was between 4 mm and 10 mm; and in 21, it was greater than 10 mm. The incidence of pleural effusions was higher after upper-abdominal surgery, in patients with postoperative atelectasis, on the side on which the surgery was performed, and in patients with free abdominal fluid. Thoracocentesis was performed on 20 patients, and in 16 patients the effusions were exudates. All of the effusions resolved without specific therapy except one. The pleural fluid in this patient was characterized by a low pH (6.93) and positive culture for Staphylococcus aureus. Small pleural effusions are common after abdominal surgery, and most resolve spontaneously within a few days.", "contents": "Incidence and significance of pleural effusion after abdominal surgery. Two hundred patients who had undergone abdominal surgery received bilateral decubitus chest roentgenograms between 48 and 72 hours after surgery to evaluate the incidence of pleural effusion after abdominal surgery. Ninety-seven (49 percent) had some pleural fluid visible on the x-ray films. In 50 patients the thickness of the fluid was less than 4 mm on the decubitus film; in 26, it was between 4 mm and 10 mm; and in 21, it was greater than 10 mm. The incidence of pleural effusions was higher after upper-abdominal surgery, in patients with postoperative atelectasis, on the side on which the surgery was performed, and in patients with free abdominal fluid. Thoracocentesis was performed on 20 patients, and in 16 patients the effusions were exudates. All of the effusions resolved without specific therapy except one. The pleural fluid in this patient was characterized by a low pH (6.93) and positive culture for Staphylococcus aureus. Small pleural effusions are common after abdominal surgery, and most resolve spontaneously within a few days."} {"id": "PMID:1269270", "title": "Living cytology: A new diagnostic technique for malignant pleural effusions.", "content": "The efficacy of a new tissue-culture technique for the diagnosis of malignant pleural effusions was contrasted with conventional cytologic methods. The new technique is based on the ability of the tissue-culture medium to transform mesothelial cells into fibroblasts while not sustaining lymphoreticular cells. Against a background of fibroblasts, islets of adenocarcinoma are easily identified. Of 20 patients with pleural effusions and solid tumors, the tissue-culture technique correctly diagnosed eight (40 percent), compated to seven (35 percent) for conventional cytologic methods. Of 27 pleural effusions in patients without malignant neoplasms, there was only one probable false-positive.", "contents": "Living cytology: A new diagnostic technique for malignant pleural effusions. The efficacy of a new tissue-culture technique for the diagnosis of malignant pleural effusions was contrasted with conventional cytologic methods. The new technique is based on the ability of the tissue-culture medium to transform mesothelial cells into fibroblasts while not sustaining lymphoreticular cells. Against a background of fibroblasts, islets of adenocarcinoma are easily identified. Of 20 patients with pleural effusions and solid tumors, the tissue-culture technique correctly diagnosed eight (40 percent), compated to seven (35 percent) for conventional cytologic methods. Of 27 pleural effusions in patients without malignant neoplasms, there was only one probable false-positive."} {"id": "PMID:1269271", "title": "Congenital tricuspid insufficiency. Definition and review.", "content": "Simple congenital tricuspid insufficiency (CTI) has, up to now, been loosely included with the larger Ebstein's anomaly (EA) group. Certain pathologic and clinical features of CTI deserve definition and a place apart from EA. A review of the literature has produced 20 clinical cases for analysis to which we add two cases successfully treated surgically. The high mortality in the neonatal age group (14 of 14) continues to be a formidable challenge, but the older survivors (2 of 8) would appear to have better prospects, based on our limited experience.", "contents": "Congenital tricuspid insufficiency. Definition and review. Simple congenital tricuspid insufficiency (CTI) has, up to now, been loosely included with the larger Ebstein's anomaly (EA) group. Certain pathologic and clinical features of CTI deserve definition and a place apart from EA. A review of the literature has produced 20 clinical cases for analysis to which we add two cases successfully treated surgically. The high mortality in the neonatal age group (14 of 14) continues to be a formidable challenge, but the older survivors (2 of 8) would appear to have better prospects, based on our limited experience."} {"id": "PMID:1269272", "title": "Sites of entrance block and impulse formation in intermittent atrioventricular junctional parasystole.", "content": "The Wenckebach phenomenon of entrance block in intermittent atrioventricular junctional parasystole is reported for the first time in a 40-year-old woman. In this case the presence of dual pathways in the atrioventricular junction is demonstrated. One of them is a pathway without conduction disturbance. The other is a pathway containing both the ectopic focus and the site of second-degree entrance block. This site is located a considerably long distance above the focus. Entrance block occurs also at some site below the ectopic focus, which is a part of the pathway containing the focus. It is suggested that entrance block in this lower site might exist during the whole ectopic cycle.", "contents": "Sites of entrance block and impulse formation in intermittent atrioventricular junctional parasystole. The Wenckebach phenomenon of entrance block in intermittent atrioventricular junctional parasystole is reported for the first time in a 40-year-old woman. In this case the presence of dual pathways in the atrioventricular junction is demonstrated. One of them is a pathway without conduction disturbance. The other is a pathway containing both the ectopic focus and the site of second-degree entrance block. This site is located a considerably long distance above the focus. Entrance block occurs also at some site below the ectopic focus, which is a part of the pathway containing the focus. It is suggested that entrance block in this lower site might exist during the whole ectopic cycle."} {"id": "PMID:1269273", "title": "Ventriculography and coronary arteriography in the acutely III patient. Complications, extent of coronary arterial disease, and abnormalities of left ventricular function.", "content": "Of 99 patients who underwent \"emergency\" diagnostic studies, 82 had \"unstable angina\" (group A), 15 had recent myocardial infarction (group B), and two had intractable congestive heart failure due to acute mitral regurgitation (group C). Two cardiac and two local complications occurred either during the procedure or during the following 48 hours. There were no deaths or myocardial infarctions. Ten (12 percent) patients of group A had \"normal\" coronary arteries and normal left ventricular function; 13, 26 and 33 patients had one, two, and three coronary arteries involved, respectively. Those with three-vessel disease had a significantly higher left ventricular end-diastolic pressure (LVEDP) and lower ejection fraction (EF) than those with one- and two-vessel disease. Those with previous myocardial infarction had a significantly higher incidence of reduced EF and of wall motion abnormalities than those without a previous myocardial infarction. All patients in group B had significant coronary arterial disease, and 80 percent (12) had abnormal left ventricular function. Their mean LVEDP and EF were significantly higher and lower, respectively, than those found in group A. In conclusion, acutely ill patients were studied with low risk. Most patients had three- or two-vessel disease. Abnormal left ventricular function was related to three-vessel disease and to recent and old myocardial infarction.", "contents": "Ventriculography and coronary arteriography in the acutely III patient. Complications, extent of coronary arterial disease, and abnormalities of left ventricular function. Of 99 patients who underwent \"emergency\" diagnostic studies, 82 had \"unstable angina\" (group A), 15 had recent myocardial infarction (group B), and two had intractable congestive heart failure due to acute mitral regurgitation (group C). Two cardiac and two local complications occurred either during the procedure or during the following 48 hours. There were no deaths or myocardial infarctions. Ten (12 percent) patients of group A had \"normal\" coronary arteries and normal left ventricular function; 13, 26 and 33 patients had one, two, and three coronary arteries involved, respectively. Those with three-vessel disease had a significantly higher left ventricular end-diastolic pressure (LVEDP) and lower ejection fraction (EF) than those with one- and two-vessel disease. Those with previous myocardial infarction had a significantly higher incidence of reduced EF and of wall motion abnormalities than those without a previous myocardial infarction. All patients in group B had significant coronary arterial disease, and 80 percent (12) had abnormal left ventricular function. Their mean LVEDP and EF were significantly higher and lower, respectively, than those found in group A. In conclusion, acutely ill patients were studied with low risk. Most patients had three- or two-vessel disease. Abnormal left ventricular function was related to three-vessel disease and to recent and old myocardial infarction."} {"id": "PMID:1269274", "title": "The effect of respiratory motion on the echocardiogram.", "content": "The effects of respiratory movements on the ultrasonic echoes of the cardiac structures were recorded and analyzed in 50 consecutive patients. Deep inspiration in cooperative patients resulted in a considerable increase of dense anterior echoes, with blotting out of any distal or posterior echoes in 12 of 44 patients (group A). In the second or larger series (32 of 44 patients; group B), a posterior displacement of most of the identifiable intrinsic cardiac echoes was seen with deep inspiration, particularly those of the posterior wall of the left ventricle. Forced expiration produced an opposite or anterior displacement of the cardiac echoes. Normal respirations showed similar but smaller excursions.", "contents": "The effect of respiratory motion on the echocardiogram. The effects of respiratory movements on the ultrasonic echoes of the cardiac structures were recorded and analyzed in 50 consecutive patients. Deep inspiration in cooperative patients resulted in a considerable increase of dense anterior echoes, with blotting out of any distal or posterior echoes in 12 of 44 patients (group A). In the second or larger series (32 of 44 patients; group B), a posterior displacement of most of the identifiable intrinsic cardiac echoes was seen with deep inspiration, particularly those of the posterior wall of the left ventricle. Forced expiration produced an opposite or anterior displacement of the cardiac echoes. Normal respirations showed similar but smaller excursions."} {"id": "PMID:1269275", "title": "The role of hypovolemic stress in the production of fat embolism in rabbits. 2. Changes in arterial blood gas levels and static compliance.", "content": "The purpose of this study was to assess the possible role of hypovolemia as a factor in the production of impaired pulmonary function in pulmonary fat embolizaiton. Iv vivo static lung compliance was measured by inflating the lungs with known volumes of air and recording the transpulmonary pressure, monitoring intraesophageal pressure as an index of intrapleural pressure. Arterial blood was drawn from the central artery of the ear. Embolization was produced by the intravenous injection of homologous fat cells either as the sole experimental procedure or in conjunction with hypovolemic shock. Two types of shock were studied. In one, 20 percent of the blood volume was removed, producing hypovolemia associated with hemodilution, and in the other a tourniquet was applied to induce hypovolemia and hemoconcentration. The results indicate that embolization is associated with significantly greater impairment of pulmonary function if it develops on a background of shock than if it occurs in an otherwise healthy animal. These pathophysiologic findings parallel the results of a morphologic study.", "contents": "The role of hypovolemic stress in the production of fat embolism in rabbits. 2. Changes in arterial blood gas levels and static compliance. The purpose of this study was to assess the possible role of hypovolemia as a factor in the production of impaired pulmonary function in pulmonary fat embolizaiton. Iv vivo static lung compliance was measured by inflating the lungs with known volumes of air and recording the transpulmonary pressure, monitoring intraesophageal pressure as an index of intrapleural pressure. Arterial blood was drawn from the central artery of the ear. Embolization was produced by the intravenous injection of homologous fat cells either as the sole experimental procedure or in conjunction with hypovolemic shock. Two types of shock were studied. In one, 20 percent of the blood volume was removed, producing hypovolemia associated with hemodilution, and in the other a tourniquet was applied to induce hypovolemia and hemoconcentration. The results indicate that embolization is associated with significantly greater impairment of pulmonary function if it develops on a background of shock than if it occurs in an otherwise healthy animal. These pathophysiologic findings parallel the results of a morphologic study."} {"id": "PMID:1269279", "title": "Radionuclide angiocardiographic measurement of left ventricular volume and ejection fraction.", "content": "In recent years a number of different radionuclidic techniques have been developed to measure left ventricular volume and ejection fraction. Area-measurement concepts have been applied to static and electrocardiographically gated radionuclidic images which have resulted in accurate measurement of left ventricular end-diastolic volume (LVEDV) and ejection fraction (LVEF). Gated (end-diastolic and end-systolic) image analysis has also proven capable of detecting regional left ventricular wallmotion abnormalities in patients with coronary disease. Time-activity curves can be extracted from left ventricular images, and several dynamic techniques have been developed and have also resulted in accurate measurement of LVEDV and LVEF. Radionuclide methods are currently available which are accurate and atraumatic and consequently applicable to the serial study of patients with heart disease. In particular, several of these radionuclide methods are relatively inexpensive and should be able to be performed in most hospitals.", "contents": "Radionuclide angiocardiographic measurement of left ventricular volume and ejection fraction. In recent years a number of different radionuclidic techniques have been developed to measure left ventricular volume and ejection fraction. Area-measurement concepts have been applied to static and electrocardiographically gated radionuclidic images which have resulted in accurate measurement of left ventricular end-diastolic volume (LVEDV) and ejection fraction (LVEF). Gated (end-diastolic and end-systolic) image analysis has also proven capable of detecting regional left ventricular wallmotion abnormalities in patients with coronary disease. Time-activity curves can be extracted from left ventricular images, and several dynamic techniques have been developed and have also resulted in accurate measurement of LVEDV and LVEF. Radionuclide methods are currently available which are accurate and atraumatic and consequently applicable to the serial study of patients with heart disease. In particular, several of these radionuclide methods are relatively inexpensive and should be able to be performed in most hospitals."} {"id": "PMID:1269280", "title": "Pericarditis with effusion casued by Actinomyces israelii.", "content": "Actinomyces israelii is a rare cause of pericarditis. Infection spreads to pericardium from an intrathoracic focus. Branching gram-positive filaments are seen on microscopic examination of clinical specimens. Cultures should be performed under anaerobic conditions. Both surgical drainage and antibiotics (penicillin) are required for treatment. Nocardiosis may resemble actinomycosis in many respects.", "contents": "Pericarditis with effusion casued by Actinomyces israelii. Actinomyces israelii is a rare cause of pericarditis. Infection spreads to pericardium from an intrathoracic focus. Branching gram-positive filaments are seen on microscopic examination of clinical specimens. Cultures should be performed under anaerobic conditions. Both surgical drainage and antibiotics (penicillin) are required for treatment. Nocardiosis may resemble actinomycosis in many respects."} {"id": "PMID:1269281", "title": "Primary diffuse pulmonary amyloidosis with monoclonal gammopathy.", "content": "A rare case of primary diffuse amyloidosis of the lung with an abnormal monoclonal protein is described. The diagnosis was confirmed by an open-lung biopsy. The different classifications of amyloidosis as well as the relationship between the immunoglobulins and the pathogenesis of amyloid disease is discussed.", "contents": "Primary diffuse pulmonary amyloidosis with monoclonal gammopathy. A rare case of primary diffuse amyloidosis of the lung with an abnormal monoclonal protein is described. The diagnosis was confirmed by an open-lung biopsy. The different classifications of amyloidosis as well as the relationship between the immunoglobulins and the pathogenesis of amyloid disease is discussed."} {"id": "PMID:1269282", "title": "Echocardiographic manifestations of aortic cusp rupture in a myxomatous aortic valve.", "content": "A 16-year-old pregnant black girl who had spontaneous perforation of the aortic valve associated with myxomatous aortic valvular degeneration is presented. The echocardiogram revealed chaotic systolic motion of one of the aortic cusps, diastolic aortic valvular fluttering, and abnormal diastolic echoes in the left ventricular outflow tract. The report illustrates that the echocardiographic features associated with valvular vegetations are not specific for infectious endocarditis.", "contents": "Echocardiographic manifestations of aortic cusp rupture in a myxomatous aortic valve. A 16-year-old pregnant black girl who had spontaneous perforation of the aortic valve associated with myxomatous aortic valvular degeneration is presented. The echocardiogram revealed chaotic systolic motion of one of the aortic cusps, diastolic aortic valvular fluttering, and abnormal diastolic echoes in the left ventricular outflow tract. The report illustrates that the echocardiographic features associated with valvular vegetations are not specific for infectious endocarditis."} {"id": "PMID:1269283", "title": "Total anomalous pulmonary venous return. Successful total correction in a 44-year-old man with subtotal absence of interatrial septum, tricuspid insufficiency, and cardiac dextroversion.", "content": "A case of total anomalous pulmonary venous return, virtual absence of the interatrial septum, cardiac dextroversion, and tricuspid insufficiency with total correction at age 44 years is presented. Repeat catheterization four months after surgery showed normal hemodynamics and pulmonary vascular resistance. The physiologic and anatomic factors allowing survival and total surgical correction at such a late age are reviewed.", "contents": "Total anomalous pulmonary venous return. Successful total correction in a 44-year-old man with subtotal absence of interatrial septum, tricuspid insufficiency, and cardiac dextroversion. A case of total anomalous pulmonary venous return, virtual absence of the interatrial septum, cardiac dextroversion, and tricuspid insufficiency with total correction at age 44 years is presented. Repeat catheterization four months after surgery showed normal hemodynamics and pulmonary vascular resistance. The physiologic and anatomic factors allowing survival and total surgical correction at such a late age are reviewed."} {"id": "PMID:1269284", "title": "Systolic anterior motion of the mitral valve without asymmetric septal hypertrophy.", "content": "This report describes a patient with echocardiographic systolic anterior motion of the mitral valve causing the anterior mitral leaflet to contact the septum in systole. At necropsy a normal nonhypertrophied heart with normal-sized ventricular cavities and a normal outflow tract and mitral valve was found. Thus, asymmetric septal hypertrophy and abnormal mitral valvular placement are not requisites for systolic anterior motion of the mitral valve. During systole, a marked forward movement of the anterior mitral leaflet developed in our patient in the setting of hypovolemia and continuous intravenous administration of pressor drugs, suggesting, rather, that systolic anterior motion reflects a small, vigorously contracting ventricular cavity and that such dynamic subaortic obstruction is not pathognomonic of idiopathic hypertrophic subaortic stenosis.", "contents": "Systolic anterior motion of the mitral valve without asymmetric septal hypertrophy. This report describes a patient with echocardiographic systolic anterior motion of the mitral valve causing the anterior mitral leaflet to contact the septum in systole. At necropsy a normal nonhypertrophied heart with normal-sized ventricular cavities and a normal outflow tract and mitral valve was found. Thus, asymmetric septal hypertrophy and abnormal mitral valvular placement are not requisites for systolic anterior motion of the mitral valve. During systole, a marked forward movement of the anterior mitral leaflet developed in our patient in the setting of hypovolemia and continuous intravenous administration of pressor drugs, suggesting, rather, that systolic anterior motion reflects a small, vigorously contracting ventricular cavity and that such dynamic subaortic obstruction is not pathognomonic of idiopathic hypertrophic subaortic stenosis."} {"id": "PMID:1269285", "title": "Metastatic teratocarcinoma following chemotherapy. Maturation to a mass pathologically indistinguishable from a mediastinal enteric cyst.", "content": "A case of testicular teratocarcinoma metastatic to a mediastinal lymph node and associated with a mediastinal lesion indistinguishable from an enteric cyst is presented. It is postulated that the mediastinal enteric cyst-like lesion resulted from histologic maturation of metastatic teratocarcinoma after intensive chemotherapy. The basis in the medical literature for this postulate is detailed.", "contents": "Metastatic teratocarcinoma following chemotherapy. Maturation to a mass pathologically indistinguishable from a mediastinal enteric cyst. A case of testicular teratocarcinoma metastatic to a mediastinal lymph node and associated with a mediastinal lesion indistinguishable from an enteric cyst is presented. It is postulated that the mediastinal enteric cyst-like lesion resulted from histologic maturation of metastatic teratocarcinoma after intensive chemotherapy. The basis in the medical literature for this postulate is detailed."} {"id": "PMID:1269286", "title": "Coronary arteritis in systemic lupus erythematosus.", "content": "Acute myocardial infarction in systemic lupus erythematosus may be due to an atheromatous or arteritic process. Confirmation of the latter etiology has previously been made only at postmortem examination. A 45-year-old white woman with known systemic lupus erythematosus developed anginal pain and multiple episodes of acute myocardial infarction. During this period, there was serologic but no other clinical evidence of active systemic lupus erythematosus. Serial coronary angiographic studies were strongly suggestive of an arteritic process based upon (1) a saccular aneurysm with no obstructive lesions in a coronary artery supplying an area of recent transmural myocardial infarction and (2) the development of significant obstructive lesions in a previously normal coronary artery over a period of 18 days. This case illustrates the difficulties in distinguishing between atherosclerosis and arteritis using a single coronary angiographic study. The distinction is significant because of the different therapeutic interventions required.", "contents": "Coronary arteritis in systemic lupus erythematosus. Acute myocardial infarction in systemic lupus erythematosus may be due to an atheromatous or arteritic process. Confirmation of the latter etiology has previously been made only at postmortem examination. A 45-year-old white woman with known systemic lupus erythematosus developed anginal pain and multiple episodes of acute myocardial infarction. During this period, there was serologic but no other clinical evidence of active systemic lupus erythematosus. Serial coronary angiographic studies were strongly suggestive of an arteritic process based upon (1) a saccular aneurysm with no obstructive lesions in a coronary artery supplying an area of recent transmural myocardial infarction and (2) the development of significant obstructive lesions in a previously normal coronary artery over a period of 18 days. This case illustrates the difficulties in distinguishing between atherosclerosis and arteritis using a single coronary angiographic study. The distinction is significant because of the different therapeutic interventions required."} {"id": "PMID:1269288", "title": "Comparative studies of the activity of ciclacillin and dicloxacillin.", "content": "The penicillins ciclacillin and dicloxacillin demonstrate marked similarities in biological activity but, as far as can be determined, differ substantially in respect to the degree of protein binding, which is relatively low for ciclacillin and relatively high for dicloxacillin. In mice infected with Staphylococcus aureus Smith, ciclacillin is considerably more active than dicloxacillin, although both drugs are similarly effective in vitro and similarly absorbed and eliminated in vivo. The high degree of protein binding exhibited by dicloxacillin could therefore very probably explain its relatively low chemotherapeutic activity. Moreover, the in vitro and in vivo findings of the study are inconsistent with the tenets of the tau/2 thesis.", "contents": "Comparative studies of the activity of ciclacillin and dicloxacillin. The penicillins ciclacillin and dicloxacillin demonstrate marked similarities in biological activity but, as far as can be determined, differ substantially in respect to the degree of protein binding, which is relatively low for ciclacillin and relatively high for dicloxacillin. In mice infected with Staphylococcus aureus Smith, ciclacillin is considerably more active than dicloxacillin, although both drugs are similarly effective in vitro and similarly absorbed and eliminated in vivo. The high degree of protein binding exhibited by dicloxacillin could therefore very probably explain its relatively low chemotherapeutic activity. Moreover, the in vitro and in vivo findings of the study are inconsistent with the tenets of the tau/2 thesis."} {"id": "PMID:1269289", "title": "Antibacterial susceptibility testing by the dip-slide technique: a methodological evaluation.", "content": "Antibacterial susceptibility testing of urine specimens by the dip-slide method was compared to the standardized disc diffusion method. A boarder line of 12 mm inhibition zone on the slide could be used to select strains resistant to sulphisadimidine, ampicillin, nitrofurantoin or nalidixic acid. In the case of the sulphonamide, the results were grewtly influenced by composition of the medium. Susceptibility testing with the dip-slide method seems to be a useful test to differentiate strains likely to respond to therapy from resistant strains.", "contents": "Antibacterial susceptibility testing by the dip-slide technique: a methodological evaluation. Antibacterial susceptibility testing of urine specimens by the dip-slide method was compared to the standardized disc diffusion method. A boarder line of 12 mm inhibition zone on the slide could be used to select strains resistant to sulphisadimidine, ampicillin, nitrofurantoin or nalidixic acid. In the case of the sulphonamide, the results were grewtly influenced by composition of the medium. Susceptibility testing with the dip-slide method seems to be a useful test to differentiate strains likely to respond to therapy from resistant strains."} {"id": "PMID:1269290", "title": "In vitro and in vivo studies of the action of rifampicin, clofazimine and B1912 on Mycobacterium marinum.", "content": "Rifampicin (RMP) and two riminophenazine compounds (B663 and B1912) suppressed the growth of Mycobacterium marinum in vitro and in a mouse footpad infection. At appropriate concentrations and dietary dosage, all three drugs showed bactericidal activity in vitro and in vivo. On the basis of minimum inhibitory concentration, RMP was considerably more active than the other two substances in vitro. However, the rate of bactericidal effect was similar for all three drugs. In vivo, the minimum bactericidal dietary dosages of RMP, B663 and B1912 were 0.03, 0.03 and less than or equal to 0.01%, respectively. Results suggest that these drugs may be of value for the treatment of clinical M. marinum infections.", "contents": "In vitro and in vivo studies of the action of rifampicin, clofazimine and B1912 on Mycobacterium marinum. Rifampicin (RMP) and two riminophenazine compounds (B663 and B1912) suppressed the growth of Mycobacterium marinum in vitro and in a mouse footpad infection. At appropriate concentrations and dietary dosage, all three drugs showed bactericidal activity in vitro and in vivo. On the basis of minimum inhibitory concentration, RMP was considerably more active than the other two substances in vitro. However, the rate of bactericidal effect was similar for all three drugs. In vivo, the minimum bactericidal dietary dosages of RMP, B663 and B1912 were 0.03, 0.03 and less than or equal to 0.01%, respectively. Results suggest that these drugs may be of value for the treatment of clinical M. marinum infections."} {"id": "PMID:1269291", "title": "Cytological and cytochemical analysis of the effects of cis-dichlorodiamino platinum (II) on chick fibroblasts cultivated in vitro.", "content": "Chick embryo fibroblasts cultivated in vitro and treated with cis-dichlorodiamino platinum (II) have been analysed by cytological and cytochemical methods. Morphological alterations (in the nucleoli, in the chromatin and in the cytoplasm), inhibition of DNA and RNA syntheses and of cell multiplication have been noted. Under some conditions, cells are blocked just before entering into mitosis (G2 block) and can become polyploid. A high degree of cell degeneration has also been observed.", "contents": "Cytological and cytochemical analysis of the effects of cis-dichlorodiamino platinum (II) on chick fibroblasts cultivated in vitro. Chick embryo fibroblasts cultivated in vitro and treated with cis-dichlorodiamino platinum (II) have been analysed by cytological and cytochemical methods. Morphological alterations (in the nucleoli, in the chromatin and in the cytoplasm), inhibition of DNA and RNA syntheses and of cell multiplication have been noted. Under some conditions, cells are blocked just before entering into mitosis (G2 block) and can become polyploid. A high degree of cell degeneration has also been observed."} {"id": "PMID:1269292", "title": "Bacteriostatic and bactericidal activity of two trimethoprim-sulfonamide combinations.", "content": "Sulfamoxole (SDMO) has the same half-life of elimination from human plasma as sulfamethoxazole. Its antibacterial properties, however, are often inferior to those of co-trimoxazole. Its less pronounced antibacterial effect, especially against gram-negative pathogens, also becomes evident in the combination with trimethoprim (TM). The inhibition zones are often smaller around discs containing the same amount of the components SDMO/TM as those with co-trimoxazole and the inhibitory concentrations needed are frequently 2-4 times higher, especially against gram-negative bacteria, such as Escherichia coli and Proteus vulgaris. Accordingly, the curative doses 50% of the new combination are 2-3 times higher than those of co-trimoxazole in experimental infections with E. coli and P. vulgaris in mice. The bactericidal action in human urine, collected after a course of treatment with the combination SDMO/TM in the planned lower dosage, is not only often retarded, but also frequently incomplete in comparison with that in urine after co-trimoxazole in standard dosage. Clinically, this might lead to increased development of resistance or to an increase of recurrent infections.", "contents": "Bacteriostatic and bactericidal activity of two trimethoprim-sulfonamide combinations. Sulfamoxole (SDMO) has the same half-life of elimination from human plasma as sulfamethoxazole. Its antibacterial properties, however, are often inferior to those of co-trimoxazole. Its less pronounced antibacterial effect, especially against gram-negative pathogens, also becomes evident in the combination with trimethoprim (TM). The inhibition zones are often smaller around discs containing the same amount of the components SDMO/TM as those with co-trimoxazole and the inhibitory concentrations needed are frequently 2-4 times higher, especially against gram-negative bacteria, such as Escherichia coli and Proteus vulgaris. Accordingly, the curative doses 50% of the new combination are 2-3 times higher than those of co-trimoxazole in experimental infections with E. coli and P. vulgaris in mice. The bactericidal action in human urine, collected after a course of treatment with the combination SDMO/TM in the planned lower dosage, is not only often retarded, but also frequently incomplete in comparison with that in urine after co-trimoxazole in standard dosage. Clinically, this might lead to increased development of resistance or to an increase of recurrent infections."} {"id": "PMID:1269293", "title": "Responses of hyperactive boys to a behaviorally focused school attitude questionnaire.", "content": "The Teacher Approval-Disapproval Scale was administered to three groups of elementary school boys: those considered by a teacher as hyperactive and referrable; those considered as among the most active but not referrable; and normoactive classmates. The three groups of boys differed significantly in their responses to 8 of 11 individual scale items, which ask the child about the amount of teacher approval and disapproval directed toward himself personally or about the frequency of his own happiness and unhappiness in the classroom. The three groups of boys differed significantly on only 2 of 11 countepart class items, which ask the child about teacher behaviors toward the class as a whole or about the happiness and unhappiness of the entire class. The hyperactive boys said they received significantly less approval from m teachers from academic, motivational, and social behaviors than did the normoactive boys and significantly more general disapproval. The present study is among the few that report differences between hyperactive and comparison groups on self-report questionnaires. The results suggest that what appears to be greater teacher disapproval of boys than of girls may in fact be simply greater teacher disapproval of children with disruptive behavior problems, most of whom are boys.", "contents": "Responses of hyperactive boys to a behaviorally focused school attitude questionnaire. The Teacher Approval-Disapproval Scale was administered to three groups of elementary school boys: those considered by a teacher as hyperactive and referrable; those considered as among the most active but not referrable; and normoactive classmates. The three groups of boys differed significantly in their responses to 8 of 11 individual scale items, which ask the child about the amount of teacher approval and disapproval directed toward himself personally or about the frequency of his own happiness and unhappiness in the classroom. The three groups of boys differed significantly on only 2 of 11 countepart class items, which ask the child about teacher behaviors toward the class as a whole or about the happiness and unhappiness of the entire class. The hyperactive boys said they received significantly less approval from m teachers from academic, motivational, and social behaviors than did the normoactive boys and significantly more general disapproval. The present study is among the few that report differences between hyperactive and comparison groups on self-report questionnaires. The results suggest that what appears to be greater teacher disapproval of boys than of girls may in fact be simply greater teacher disapproval of children with disruptive behavior problems, most of whom are boys."} {"id": "PMID:1269294", "title": "Coping with fatherhood: the first year.", "content": "Fantasy (thinking back to prebaby times) and holidays (going out alone with the wife) are examined here as methods of coping with parenthood for 93 white, first-time fathers. Results suggest that only the holiday coping mechanism is associated with maintaining or improving marital satisfaction. The use of fantasy actually decreases marital satisfaction. These data suggest that the discrepancies in the conclusions of previous \"parenthood as crisis\" studies may be accounted for through the analysis of coping mechanisms that various fathers utilize.", "contents": "Coping with fatherhood: the first year. Fantasy (thinking back to prebaby times) and holidays (going out alone with the wife) are examined here as methods of coping with parenthood for 93 white, first-time fathers. Results suggest that only the holiday coping mechanism is associated with maintaining or improving marital satisfaction. The use of fantasy actually decreases marital satisfaction. These data suggest that the discrepancies in the conclusions of previous \"parenthood as crisis\" studies may be accounted for through the analysis of coping mechanisms that various fathers utilize."} {"id": "PMID:1269295", "title": "Embryonic mania.", "content": "It has been previously hypothesized that hyperactivity may be one childhood form of manic-depressive disorder. The authors contend that it is unlikely that hyperactivity in general is a childhood form of manic-depressive disorder. However, included in those considered to be hyperactive may be youngsters exhibiting an embryonic form of mania. A case of a 5-year-old boy, originally thought to be hyperactive, is presented as evidence for the existence of an embryonic stage of mania. The clinical and research necessity for differentiating between hyperactivity and embryonic mania is stressed.", "contents": "Embryonic mania. It has been previously hypothesized that hyperactivity may be one childhood form of manic-depressive disorder. The authors contend that it is unlikely that hyperactivity in general is a childhood form of manic-depressive disorder. However, included in those considered to be hyperactive may be youngsters exhibiting an embryonic form of mania. A case of a 5-year-old boy, originally thought to be hyperactive, is presented as evidence for the existence of an embryonic stage of mania. The clinical and research necessity for differentiating between hyperactivity and embryonic mania is stressed."} {"id": "PMID:1269296", "title": "Some comments on the significance and development of midline behavior during infancy.", "content": "With the waning of the tonic neck reflex beginning with the 8th to 12th week, and disappearing, in most instances, by the 16th week, the infant begins to become bilateral and makes symmetrical movements and engages his hands in the midline usually over the chest while in a supine position. The developmental significance of such behavior is considered--for example, its participation in the emerging sense of self and its role in the consolidation of emerging ego skills. Consideration is given to the possible implications of faulty midline behavior for development, and to whether failure to engage in an optimal amount of midline behavior, in interaction with other factors, can be used to alert observers to possible future developmental disturbances.", "contents": "Some comments on the significance and development of midline behavior during infancy. With the waning of the tonic neck reflex beginning with the 8th to 12th week, and disappearing, in most instances, by the 16th week, the infant begins to become bilateral and makes symmetrical movements and engages his hands in the midline usually over the chest while in a supine position. The developmental significance of such behavior is considered--for example, its participation in the emerging sense of self and its role in the consolidation of emerging ego skills. Consideration is given to the possible implications of faulty midline behavior for development, and to whether failure to engage in an optimal amount of midline behavior, in interaction with other factors, can be used to alert observers to possible future developmental disturbances."} {"id": "PMID:1269303", "title": "Perception as a possible source of conservation: evidence for length conservation.", "content": "In conservation problems, it is commonly assumed that equivalence judgments are not facilitated by observation of the stimuli following transformation. The reverse is usually assumed to be the case. These assumptions were tested in a training experiment. Perceptual counterparts of a series of conservation of length tests were presented to subjects who were catagorized as conservers or nonconservers on conservations of length pretests, and to conservers and nonconservers given conservation of length training. Perceptual performance of the untrained nonconservers was significantly worse than that of the other 3 groups, that is, trained nonconservers, untrained conservers, and trained conservers. These findings are interpreted as consistent with the hypothesis that conservation is attained with the support of perception, not in spite of it.", "contents": "Perception as a possible source of conservation: evidence for length conservation. In conservation problems, it is commonly assumed that equivalence judgments are not facilitated by observation of the stimuli following transformation. The reverse is usually assumed to be the case. These assumptions were tested in a training experiment. Perceptual counterparts of a series of conservation of length tests were presented to subjects who were catagorized as conservers or nonconservers on conservations of length pretests, and to conservers and nonconservers given conservation of length training. Perceptual performance of the untrained nonconservers was significantly worse than that of the other 3 groups, that is, trained nonconservers, untrained conservers, and trained conservers. These findings are interpreted as consistent with the hypothesis that conservation is attained with the support of perception, not in spite of it."} {"id": "PMID:1269304", "title": "Birth order and sex of sibling as determinants of mother-infant interaction.", "content": "Mother-infant interaction was assessed on 32 first- and second-born siblings when each was 3 months old. Data were colleted during 2 6-hour naturalistic home observations using a modified time-sampling technique. The sample consisted of 4 equal-size subgroups of same and opposite sex sibling pairs. Results suggested that interaction between a mother and her infant varied depending on the birth order and gender of the infant. Mothers spent significantly less time in social, affectionate, and caretaking interaction (except for feeding activities) with their second borns than they had with their firstborns; this difference was greater if the second born was female. Certain patterns of maternal behaviors appeared to be stable from one sibling to the other. Different types of interaction between the mothers and their younger infants were related to attention-seeking behavior in the firstborn male and female siblings.", "contents": "Birth order and sex of sibling as determinants of mother-infant interaction. Mother-infant interaction was assessed on 32 first- and second-born siblings when each was 3 months old. Data were colleted during 2 6-hour naturalistic home observations using a modified time-sampling technique. The sample consisted of 4 equal-size subgroups of same and opposite sex sibling pairs. Results suggested that interaction between a mother and her infant varied depending on the birth order and gender of the infant. Mothers spent significantly less time in social, affectionate, and caretaking interaction (except for feeding activities) with their second borns than they had with their firstborns; this difference was greater if the second born was female. Certain patterns of maternal behaviors appeared to be stable from one sibling to the other. Different types of interaction between the mothers and their younger infants were related to attention-seeking behavior in the firstborn male and female siblings."} {"id": "PMID:1269305", "title": "Infants' responses to strangers: midget, adult, and child.", "content": "Infants respond differentially, and at times with fearlike behavior, to unfamiliar persons. This study was designed to see how infants discriminate among strangers. Since it has been shown that infants respond differently to children and adults, the physical characteristics of persons used to make such differentiations were of interest. Facial configuration and height were systematically varied as 4 different strangers--a male and female child, a female adults, and a small female adult the same height as the children (midget)--each approached 40 different infants. The infants responded as if there were 3 classes of persons--adult, child, and small adult, suggesting that both size and facial configuration cues were used. Infants as young as 7 months of age reacted to the size-facial configuration discrepancy of the small-adult condition.", "contents": "Infants' responses to strangers: midget, adult, and child. Infants respond differentially, and at times with fearlike behavior, to unfamiliar persons. This study was designed to see how infants discriminate among strangers. Since it has been shown that infants respond differently to children and adults, the physical characteristics of persons used to make such differentiations were of interest. Facial configuration and height were systematically varied as 4 different strangers--a male and female child, a female adults, and a small female adult the same height as the children (midget)--each approached 40 different infants. The infants responded as if there were 3 classes of persons--adult, child, and small adult, suggesting that both size and facial configuration cues were used. Infants as young as 7 months of age reacted to the size-facial configuration discrepancy of the small-adult condition."} {"id": "PMID:1269306", "title": "Serial habituation in two-, three-, and four-month-old infants.", "content": "Serial habituation of visual fixations in 2-, 3-, and 4-month-old infants was investigated through a design permitting cross-sectional, within-subject longitudinal, cohort longitudinal, and time-lag analyses. The components of the standard stimulus were displayed individually before and after successive exposures of the standard for familiarization. Relative saliencies of the components for each child were indexed by magnitude of responding to these parts in the initial presentation. Comparisons of the pre- and postexposure fixation times suggest that for all ages habituation was under way to the parts of the stimulus in orders of the relative saliencies. The nature of the data in general did not appear to be influenced significantly by any 1 methodology.", "contents": "Serial habituation in two-, three-, and four-month-old infants. Serial habituation of visual fixations in 2-, 3-, and 4-month-old infants was investigated through a design permitting cross-sectional, within-subject longitudinal, cohort longitudinal, and time-lag analyses. The components of the standard stimulus were displayed individually before and after successive exposures of the standard for familiarization. Relative saliencies of the components for each child were indexed by magnitude of responding to these parts in the initial presentation. Comparisons of the pre- and postexposure fixation times suggest that for all ages habituation was under way to the parts of the stimulus in orders of the relative saliencies. The nature of the data in general did not appear to be influenced significantly by any 1 methodology."} {"id": "PMID:1269307", "title": "A study of the \"inversion of intensity\" between newborn and preschool-age behavior.", "content": "To test the inversion of intensity interpretation based on negative relations between newborn and preschool intensity behaviors (Bell, Weller, & Waldrop 1971), 106 normal children were examined at the neonatal and preschool periods. Data analyses were carried out in 2 parts: Part I was an attempt to reconstruct the same measures of intensity Bell et al. used at both periods, and Part II was a broader factor analytic analysis using all measures conceptually related to intensity in the neonatal and preschool periods. In Part I, several correlations were in the direction consistent with inversion, but only 1 of 20 correlations reached significance. In Part II, several significant correlations between intensity behavior at newborn and preschool periods were obtained, indicating intense newborn behavior to be related to low levels of socially negative behaviors. Interpretations of intensity behaviors at both periods and their longitudinal relations are discussed.", "contents": "A study of the \"inversion of intensity\" between newborn and preschool-age behavior. To test the inversion of intensity interpretation based on negative relations between newborn and preschool intensity behaviors (Bell, Weller, & Waldrop 1971), 106 normal children were examined at the neonatal and preschool periods. Data analyses were carried out in 2 parts: Part I was an attempt to reconstruct the same measures of intensity Bell et al. used at both periods, and Part II was a broader factor analytic analysis using all measures conceptually related to intensity in the neonatal and preschool periods. In Part I, several correlations were in the direction consistent with inversion, but only 1 of 20 correlations reached significance. In Part II, several significant correlations between intensity behavior at newborn and preschool periods were obtained, indicating intense newborn behavior to be related to low levels of socially negative behaviors. Interpretations of intensity behaviors at both periods and their longitudinal relations are discussed."} {"id": "PMID:1269308", "title": "Body size and form of black and white female youths measured during 1974-1975 at Columbia, South Carolina.", "content": "From original data at age 13 years on 386 North American females (201 black and 185 white), statistics are presented for 10 somatic variables. The 2 ethnic groups yield similar means for standing height, arm girth, and leg girth; the black females, contrasted with their white peers, are shorter in sitting height, longer in lower limb height, and narrower in hip width. The Columbia subjects are compared with black and white females studied in North America several decades ago, and with black and white females studied recently in other parts of North America and in Australia, Europe, Africa, and the Lesser Antilles.", "contents": "Body size and form of black and white female youths measured during 1974-1975 at Columbia, South Carolina. From original data at age 13 years on 386 North American females (201 black and 185 white), statistics are presented for 10 somatic variables. The 2 ethnic groups yield similar means for standing height, arm girth, and leg girth; the black females, contrasted with their white peers, are shorter in sitting height, longer in lower limb height, and narrower in hip width. The Columbia subjects are compared with black and white females studied in North America several decades ago, and with black and white females studied recently in other parts of North America and in Australia, Europe, Africa, and the Lesser Antilles."} {"id": "PMID:1269309", "title": "Self-evaluation, social reinforcement, and academic achievement of black and white schoolchildren.", "content": "Black and white male schoolchildren covertly evaluated their own performance at a verbal task administered by black and white male experimenters. It was hypothesized that academically successful children would be predisposed to appraise themselves favorably, whereas relatively unsuccessful pupils would be biased toward self-criticism. The covert self-evaluations were assumed to represent at internalization of early experiences of predominantly positive or negative social reinforcement from adult socializing agents. The predicition for self-criticism was upheld in the white experimenter condition but not in the black experimenter condition. Relationships consistent with the theory were found between subjects' self-appraisals and their retrospective reports of positive and negative reinforcements received from parents and teachers in various typical situations. These relationships were more evident for black subjects than for white subjects. The extent to which children's self-praise and self-criticism mediated affect was assessed by means of a color conditioning technique. Contrary to predicition, possibly due to the easy nature of the experimental task.", "contents": "Self-evaluation, social reinforcement, and academic achievement of black and white schoolchildren. Black and white male schoolchildren covertly evaluated their own performance at a verbal task administered by black and white male experimenters. It was hypothesized that academically successful children would be predisposed to appraise themselves favorably, whereas relatively unsuccessful pupils would be biased toward self-criticism. The covert self-evaluations were assumed to represent at internalization of early experiences of predominantly positive or negative social reinforcement from adult socializing agents. The predicition for self-criticism was upheld in the white experimenter condition but not in the black experimenter condition. Relationships consistent with the theory were found between subjects' self-appraisals and their retrospective reports of positive and negative reinforcements received from parents and teachers in various typical situations. These relationships were more evident for black subjects than for white subjects. The extent to which children's self-praise and self-criticism mediated affect was assessed by means of a color conditioning technique. Contrary to predicition, possibly due to the easy nature of the experimental task."} {"id": "PMID:1269310", "title": "The effects of cooperatively and competitively structured learning enironments on inter- and intrapersonal behavior.", "content": "This study examines the effects of cooperative versus competitive goal structures on the subsequent intra- and interpersonal behavior of fourth-grade children. 2 situational variables were operating in each situation: first, the variable of working on a project as a group versus as an individual; and second, the variable of public reward. Results indicate that the effects of competitively structured environments differ for winners and nonwinners and for boys and girls. Girls, both winners and nonwinners, adopt the evaluations of the experimenter and generalize worthiness or deservedness to other situations as evidenced by their prize giving to self and others. After failure to win, girls also refrain from taking a toy away from the winner. After failure to win, boys behave competitively by taking a toy away from the winner and rewarding self more relative to others. The data also suggest that boys may not have experienced cooperative winning as success.", "contents": "The effects of cooperatively and competitively structured learning enironments on inter- and intrapersonal behavior. This study examines the effects of cooperative versus competitive goal structures on the subsequent intra- and interpersonal behavior of fourth-grade children. 2 situational variables were operating in each situation: first, the variable of working on a project as a group versus as an individual; and second, the variable of public reward. Results indicate that the effects of competitively structured environments differ for winners and nonwinners and for boys and girls. Girls, both winners and nonwinners, adopt the evaluations of the experimenter and generalize worthiness or deservedness to other situations as evidenced by their prize giving to self and others. After failure to win, girls also refrain from taking a toy away from the winner. After failure to win, boys behave competitively by taking a toy away from the winner and rewarding self more relative to others. The data also suggest that boys may not have experienced cooperative winning as success."} {"id": "PMID:1269311", "title": "The influence of moral reasoning on behavioral choices.", "content": "This study examined the ways in which exposure to moral reasoning statements affected the subsequent behavioral choices of 144 seventh-, eighth-, and ninth-grade boys at different stages of moral judgment. The subjects were divided among 4 experimental conditions, each of which attempted to isolate and relate behavioral choice and reasoning in specific ways. The presentation of reasoning had different effects on the behavioral choices of subjects at 2 different stages. The findings were considered in terms of their implications for developmental change as well as for a developmental analysis of the relationship between moral reasoning and moral behavior.", "contents": "The influence of moral reasoning on behavioral choices. This study examined the ways in which exposure to moral reasoning statements affected the subsequent behavioral choices of 144 seventh-, eighth-, and ninth-grade boys at different stages of moral judgment. The subjects were divided among 4 experimental conditions, each of which attempted to isolate and relate behavioral choice and reasoning in specific ways. The presentation of reasoning had different effects on the behavioral choices of subjects at 2 different stages. The findings were considered in terms of their implications for developmental change as well as for a developmental analysis of the relationship between moral reasoning and moral behavior."} {"id": "PMID:1269312", "title": "Children's perceptions of deviance and disorder.", "content": "First-, fourth-, seventh-, and eleventh-grade boys and girls were interviewed on the topic of deviant behavior among their peers. They were also asked to make deviance judgments on 2 story characters whose behaviors exemplified qualities that typically evoke an attribution of psychological disorder on the part of adult judges. 1 story described loss of control and aggression, the other a distorted and paranoid perception of social reality. The pattern of reaction to the stories was consistent with age-related shifts in the basic for deviant status. First graders largely failed to think in terms of group norms. The transition from the middle grades to adolescence was marked by greater emphasis on social consensus--both in psychological perspective and group behavior.", "contents": "Children's perceptions of deviance and disorder. First-, fourth-, seventh-, and eleventh-grade boys and girls were interviewed on the topic of deviant behavior among their peers. They were also asked to make deviance judgments on 2 story characters whose behaviors exemplified qualities that typically evoke an attribution of psychological disorder on the part of adult judges. 1 story described loss of control and aggression, the other a distorted and paranoid perception of social reality. The pattern of reaction to the stories was consistent with age-related shifts in the basic for deviant status. First graders largely failed to think in terms of group norms. The transition from the middle grades to adolescence was marked by greater emphasis on social consensus--both in psychological perspective and group behavior."} {"id": "PMID:1269313", "title": "Continuous vowel discrimination in normal and at risk infants.", "content": "The present study investigated vowel discrimination in 2-week-old infants using a nonnutritive, high-amplitude sucking measure in a habituation-dishabituation paradigm. Infants were presented with pairs of vowel stimuli differing in equal logarithmic steps along the /i/ to /I/ continuum. Stimulus pairs of equal acoustic differences were selected to be either within or between the adult phonetic categories. Infants were divided into 3 experimental stimulus shift conditions: within category, between category, and control. Using a scoring system to asses perinatal events, half the infants in each condition were categorized as being at \"higher risk\" for developmental (p less than .05) were found between the control and both the within and between phonetic category conditions. No effects due to risk score population differences proved to be significant. These results indicate that 8-week-old infants discriminate the vowels /i/ and /I/ in a continuous as opposed to a categorical manner. Some differences were noted in response patterns between high- and low-risk score infants.", "contents": "Continuous vowel discrimination in normal and at risk infants. The present study investigated vowel discrimination in 2-week-old infants using a nonnutritive, high-amplitude sucking measure in a habituation-dishabituation paradigm. Infants were presented with pairs of vowel stimuli differing in equal logarithmic steps along the /i/ to /I/ continuum. Stimulus pairs of equal acoustic differences were selected to be either within or between the adult phonetic categories. Infants were divided into 3 experimental stimulus shift conditions: within category, between category, and control. Using a scoring system to asses perinatal events, half the infants in each condition were categorized as being at \"higher risk\" for developmental (p less than .05) were found between the control and both the within and between phonetic category conditions. No effects due to risk score population differences proved to be significant. These results indicate that 8-week-old infants discriminate the vowels /i/ and /I/ in a continuous as opposed to a categorical manner. Some differences were noted in response patterns between high- and low-risk score infants."} {"id": "PMID:1269314", "title": "Effect of different training methods on perceptual learning in impulsive children.", "content": "The effectiveness of different training and transfer test conditions in promoting perceptual learning in impulsive kindergarten children was investigated. Interproblem variability was found to be more effective than intraproblem variability, and a differentiation training procedure was found to be more effective than a matching training procedure. The results provide guidelines for designing effective training methods for improving discrimination learning and problem solving in impulsive children.", "contents": "Effect of different training methods on perceptual learning in impulsive children. The effectiveness of different training and transfer test conditions in promoting perceptual learning in impulsive kindergarten children was investigated. Interproblem variability was found to be more effective than intraproblem variability, and a differentiation training procedure was found to be more effective than a matching training procedure. The results provide guidelines for designing effective training methods for improving discrimination learning and problem solving in impulsive children."} {"id": "PMID:1269315", "title": "Effects of exposure duration on part-whole perception in children.", "content": "Drawings of familiar objects arranged to suggest more general wholes (e.g., a beast made of pieces of fruit) were presented to 128 children aged 3-12 years, using 4 exposure durations. The ability to see both parts and wholes together improved with age, confirming earlier studies. In addition, the results suggest that limiting viewing time affects the ability to see both parts and wholes together (in a sequential, nonintegrated fashion) more in young children than in older children. The results further suggest that for younger children duration does not affect the ability to see parts and wholes in a hierarchical relationship. These results are interpreted as suggesting that at least 2 different processes mediate part-whole perception in children.", "contents": "Effects of exposure duration on part-whole perception in children. Drawings of familiar objects arranged to suggest more general wholes (e.g., a beast made of pieces of fruit) were presented to 128 children aged 3-12 years, using 4 exposure durations. The ability to see both parts and wholes together improved with age, confirming earlier studies. In addition, the results suggest that limiting viewing time affects the ability to see both parts and wholes together (in a sequential, nonintegrated fashion) more in young children than in older children. The results further suggest that for younger children duration does not affect the ability to see parts and wholes in a hierarchical relationship. These results are interpreted as suggesting that at least 2 different processes mediate part-whole perception in children."} {"id": "PMID:1269316", "title": "Children's ability to recognize other children's faces.", "content": "Facial recognition ability was studied with 288 children from 4 grades--first, second, third, and sixth--who also varied by sex race, and school type, the last being segregated or integrated. Children judged whether each of 40 pictures of children's faces had been present in a set of 20 pictures viewed earlier. Facial recognition ability increased significantly with each grade but leveled off between ages 8 and 11. Blacks' performance is significantly better than whites', and blacks are better at recognizing faces of whites than whites are at recognizing blacks. Children from an integrated school show smaller differences recognizing black or white faces than children from segregated schools, but the effect appears only for children of the integrated school who also live in mixed-race neighborhoods.", "contents": "Children's ability to recognize other children's faces. Facial recognition ability was studied with 288 children from 4 grades--first, second, third, and sixth--who also varied by sex race, and school type, the last being segregated or integrated. Children judged whether each of 40 pictures of children's faces had been present in a set of 20 pictures viewed earlier. Facial recognition ability increased significantly with each grade but leveled off between ages 8 and 11. Blacks' performance is significantly better than whites', and blacks are better at recognizing faces of whites than whites are at recognizing blacks. Children from an integrated school show smaller differences recognizing black or white faces than children from segregated schools, but the effect appears only for children of the integrated school who also live in mixed-race neighborhoods."} {"id": "PMID:1269317", "title": "A multivariate study of the effects of high-risk factors on performance on the Brazelton Neonatal Assessment Scale.", "content": "The Brazelton Neonatal Assessment Scale was administered to 52 newborn infants. A factor analysis revealed 2 main factors, 1 along an attention-orientation dimension, the other relating to temperament arousal. A stepwise multiple linear regression analysis showed that the attention-orientation factor was related to birth weight, age of the mother, and sex and race of the baby. The only variable related to the temperament-arousal factor was 5-min Apgar scor. The study, although exploratory, demonstrates the use of multivariate techniques in the assessment of influences on newborn behavior.", "contents": "A multivariate study of the effects of high-risk factors on performance on the Brazelton Neonatal Assessment Scale. The Brazelton Neonatal Assessment Scale was administered to 52 newborn infants. A factor analysis revealed 2 main factors, 1 along an attention-orientation dimension, the other relating to temperament arousal. A stepwise multiple linear regression analysis showed that the attention-orientation factor was related to birth weight, age of the mother, and sex and race of the baby. The only variable related to the temperament-arousal factor was 5-min Apgar scor. The study, although exploratory, demonstrates the use of multivariate techniques in the assessment of influences on newborn behavior."} {"id": "PMID:1269318", "title": "Neonatal nutritive sucking: effects of taste stimulation upon sucking rhythm and heart rate.", "content": "The sucking behavior and heart rate of 22 full-term newborns were recorded. Half of the infants sucked for 9 minutes in 3 blocks of 3 minutes, first receiving a 0.02-ml drop of 5% sucrose for each criterion suck, then no fluid contingent upon such sucks, and finally a 0.02-ml drop of 15% sucrose for each suck. The other half received these conditions in reverse order. Regardless of the order in which the 2 nutrient conditions were administered, intersuck intervals were longer under the sweeter condition, but heart rate was also higher. Possible interpretations include a hedonic explanation suggesting that sucking rate is modulated to facilitate savoring of the sweeter fluid.", "contents": "Neonatal nutritive sucking: effects of taste stimulation upon sucking rhythm and heart rate. The sucking behavior and heart rate of 22 full-term newborns were recorded. Half of the infants sucked for 9 minutes in 3 blocks of 3 minutes, first receiving a 0.02-ml drop of 5% sucrose for each criterion suck, then no fluid contingent upon such sucks, and finally a 0.02-ml drop of 15% sucrose for each suck. The other half received these conditions in reverse order. Regardless of the order in which the 2 nutrient conditions were administered, intersuck intervals were longer under the sweeter condition, but heart rate was also higher. Possible interpretations include a hedonic explanation suggesting that sucking rate is modulated to facilitate savoring of the sweeter fluid."} {"id": "PMID:1269319", "title": "Developmental changes in the scanning of faces by young infants.", "content": "6 1-month-old infants and 6 2-month-old infants each viewed 3 faces (his mother's, a strange woman's, and a strange man's) while his eye movements were recorded by corneal photography. The 1-month-olds fixated away from the faces most of the time, and they looked at their mothers even less often than at the strangers. When they did fixate a face, they usually chose a limited portion of the perimeter. By constrast, 2-month-olds fixated the faces most of the time, looked at more features, and were more likely to look at internal features, especially the eyes. This scanning resembles that reported previously for 2-dimensional shapes, although in some respects it appears unique to faces.", "contents": "Developmental changes in the scanning of faces by young infants. 6 1-month-old infants and 6 2-month-old infants each viewed 3 faces (his mother's, a strange woman's, and a strange man's) while his eye movements were recorded by corneal photography. The 1-month-olds fixated away from the faces most of the time, and they looked at their mothers even less often than at the strangers. When they did fixate a face, they usually chose a limited portion of the perimeter. By constrast, 2-month-olds fixated the faces most of the time, looked at more features, and were more likely to look at internal features, especially the eyes. This scanning resembles that reported previously for 2-dimensional shapes, although in some respects it appears unique to faces."} {"id": "PMID:1269320", "title": "Individual differences in habituation rates and object concept performance.", "content": "The scores from object concept tasks for 15 infants at 14 months of age were analyzed with respect to their habituation rates at 4 months of age. Partitioning of the data according to subjects categorized as fast and slow habituators brought some organization consistent with the notion that the former are more advanced than the latter. Statistical differences between groups did not obtain, but a significant correlation between ranked task scores and habituation ratios offers some support to the interpretation. The possibility of using habituation rates or ratios as an index of differences in processing, perhaps with some predictive value, may be considered if further evidence of relations to later cognitive performanceis found.", "contents": "Individual differences in habituation rates and object concept performance. The scores from object concept tasks for 15 infants at 14 months of age were analyzed with respect to their habituation rates at 4 months of age. Partitioning of the data according to subjects categorized as fast and slow habituators brought some organization consistent with the notion that the former are more advanced than the latter. Statistical differences between groups did not obtain, but a significant correlation between ranked task scores and habituation ratios offers some support to the interpretation. The possibility of using habituation rates or ratios as an index of differences in processing, perhaps with some predictive value, may be considered if further evidence of relations to later cognitive performanceis found."} {"id": "PMID:1269321", "title": "Baby drops the rattle: asymmetry of duration of grasp by infants.", "content": "Infants of mean age 2.7 months maintained grasp of a rattle for a longer mean duration with the right than the left hand, developmentally the earliest instance of asymmetry of manual dexterity and/or preference.", "contents": "Baby drops the rattle: asymmetry of duration of grasp by infants. Infants of mean age 2.7 months maintained grasp of a rattle for a longer mean duration with the right than the left hand, developmentally the earliest instance of asymmetry of manual dexterity and/or preference."} {"id": "PMID:1269322", "title": "Four- and six-month-old infants' visual responses to joy, anger, and neutral expressions.", "content": "24 infants, 12 4-month-olds and 12 6-month-olds, were repeatedly shown slides of 3 facial expressions. The expressions were previously judged by obervers to be indicators of joy, anger, and no emotion, respectively. The duration of the first visual fixation to each presentation of the slides was monitored for each subject. The data indicated that the infants looked at the joy expression significantly more than at either the anger or neutral expressions. The results suggest that infants are capable of discriminating emotion expressions earlier in their development than previous studies have implied.", "contents": "Four- and six-month-old infants' visual responses to joy, anger, and neutral expressions. 24 infants, 12 4-month-olds and 12 6-month-olds, were repeatedly shown slides of 3 facial expressions. The expressions were previously judged by obervers to be indicators of joy, anger, and no emotion, respectively. The duration of the first visual fixation to each presentation of the slides was monitored for each subject. The data indicated that the infants looked at the joy expression significantly more than at either the anger or neutral expressions. The results suggest that infants are capable of discriminating emotion expressions earlier in their development than previous studies have implied."} {"id": "PMID:1269323", "title": "Variations in intra-oral stimulation and nutritive sucking.", "content": "Sucking records were made from 24 infants, aged 3-4 days, fed small amounts of their usual formula from nipples of different sizes (5/16-, 8/16-, and 11/16-inch diam). Polygraphic and observer measures showed that the large nipple elicited fewer sucks and a slower sucking rate; 5 infants seen on 2 successive days showed a more marked nipple preference on the second day. The results show that intra-oral stimuli control sucking for a nutriment in much the same way as they have already been shown to control nonnutritive sucking.", "contents": "Variations in intra-oral stimulation and nutritive sucking. Sucking records were made from 24 infants, aged 3-4 days, fed small amounts of their usual formula from nipples of different sizes (5/16-, 8/16-, and 11/16-inch diam). Polygraphic and observer measures showed that the large nipple elicited fewer sucks and a slower sucking rate; 5 infants seen on 2 successive days showed a more marked nipple preference on the second day. The results show that intra-oral stimuli control sucking for a nutriment in much the same way as they have already been shown to control nonnutritive sucking."} {"id": "PMID:1269324", "title": "Moral reasoning from the perspective of others.", "content": "A questionnaire study was conducted to examine the ability of adolescents and college students to deliberate about moral dilemmas from social perspectives (roles) other than their own and to display different levels of moral judgment in these different perspectives. 30 subjects at each of grades 9, 10, 12, and college were administered a moral reasoning questionnaire and asked to respond 3 times--once for each of the social roles of self, average policeman, and average philosopher. Results showed that across roles and with increasing age there was an increase in individuals' tendencies to choose principled moral issues to resolve dilemmas. More important, there was an increase with age in differentiation among social roles--with the college students evidencing the greatest differences in the level of moral issues chosen as a function of social role.", "contents": "Moral reasoning from the perspective of others. A questionnaire study was conducted to examine the ability of adolescents and college students to deliberate about moral dilemmas from social perspectives (roles) other than their own and to display different levels of moral judgment in these different perspectives. 30 subjects at each of grades 9, 10, 12, and college were administered a moral reasoning questionnaire and asked to respond 3 times--once for each of the social roles of self, average policeman, and average philosopher. Results showed that across roles and with increasing age there was an increase in individuals' tendencies to choose principled moral issues to resolve dilemmas. More important, there was an increase with age in differentiation among social roles--with the college students evidencing the greatest differences in the level of moral issues chosen as a function of social role."} {"id": "PMID:1269325", "title": "Order of information presentation and children's moral judgments.", "content": "It was hypothesized that age differences in use of intent information in children's moral judgments might be due to a recency effect in the judgments of younger children. A study was conducted to examine the effect of order of stimulus presentation on children's moral judgments. The information was presented to children, ages 4-5 and 8-9 years old, through stories with either normal information order, intent-consequence, or reversed order, consequence-intent. It was found that order has a significant impact on children's moral judgments. In addition, memory data were gathered which indicated that the pattern of forgetting was parallel to the pattern of information preference for the younger subjects. The findings suggested that younger subjects' relative neglect of intent in the normal order of information was based, in part, on their failure to remember the material correctly rather than on differential weighting of the 2 cues.", "contents": "Order of information presentation and children's moral judgments. It was hypothesized that age differences in use of intent information in children's moral judgments might be due to a recency effect in the judgments of younger children. A study was conducted to examine the effect of order of stimulus presentation on children's moral judgments. The information was presented to children, ages 4-5 and 8-9 years old, through stories with either normal information order, intent-consequence, or reversed order, consequence-intent. It was found that order has a significant impact on children's moral judgments. In addition, memory data were gathered which indicated that the pattern of forgetting was parallel to the pattern of information preference for the younger subjects. The findings suggested that younger subjects' relative neglect of intent in the normal order of information was based, in part, on their failure to remember the material correctly rather than on differential weighting of the 2 cues."} {"id": "PMID:1269326", "title": "Motor activity, anticipated motor activity, and young children's associative learning.", "content": "The purpose of this study was to determine whether motor activity, previously assumed necessary to induce imagery in young children's associative learning, actually has to be executed. The results of our experiment with kindergartners clearly suggest not: In conditions where subjects simply planned to the potential motor activity (without executing it), learning was enhanced. Further, the temporal proximity of the planning to the potential motor activity did not prove to be important. These results, combined with those from 2 follow-up experiments, give rise to the speculation--among others--that young children can be \"tricked\" into imagery generation through appropriately worded instructions.", "contents": "Motor activity, anticipated motor activity, and young children's associative learning. The purpose of this study was to determine whether motor activity, previously assumed necessary to induce imagery in young children's associative learning, actually has to be executed. The results of our experiment with kindergartners clearly suggest not: In conditions where subjects simply planned to the potential motor activity (without executing it), learning was enhanced. Further, the temporal proximity of the planning to the potential motor activity did not prove to be important. These results, combined with those from 2 follow-up experiments, give rise to the speculation--among others--that young children can be \"tricked\" into imagery generation through appropriately worded instructions."} {"id": "PMID:1269341", "title": "Chromosome organisation in the Australian plague locust, Chortoicetes terminifera. 1. Banding relationships of the normal and supernumerary chromosomes.", "content": "In Chortoicetes terminifera, G-banding, produced by the trypsin treatment of air-dried slides followed by Giemsa staining, leads to light staining gaps at the secondary constrictions on autosomal pair 6 and regions proximal to the centromere on the long arms of pair 4. The variable short arms of two of the three smallest pairs were usually flared and lightly stained after treatment. In contrast to the relatively minor response of the normal chromosome set to G-banding, the large supernumerary chromosomes of C. terminifera show a spectacular series of dark bands alternating with lightly stained gaps. Two G-band variants of the B-chromosome were found in a laboratory stock. These patterns of G-banding are discernable both at mitosis in adults and embryos of both sexes and at all stages of male meiosis. Some regions which are gaps after G-banding appear as dark bands after C-banding. Consequently the supernumerary chromosome is mainly darkly stained with C-banding. In addition the centromeres and some telomeres are C-banded along with narrow interstitial bands and polymorphic heterochromatic blocks.--C-banding was not always successful, the technique often yields a mixture of G- and C-banding. The disparity of banding between the normal complement and the B-chromosome implies that whatever the source of origin of the B it has undergone spectacular changes in organisation since its origin.", "contents": "Chromosome organisation in the Australian plague locust, Chortoicetes terminifera. 1. Banding relationships of the normal and supernumerary chromosomes. In Chortoicetes terminifera, G-banding, produced by the trypsin treatment of air-dried slides followed by Giemsa staining, leads to light staining gaps at the secondary constrictions on autosomal pair 6 and regions proximal to the centromere on the long arms of pair 4. The variable short arms of two of the three smallest pairs were usually flared and lightly stained after treatment. In contrast to the relatively minor response of the normal chromosome set to G-banding, the large supernumerary chromosomes of C. terminifera show a spectacular series of dark bands alternating with lightly stained gaps. Two G-band variants of the B-chromosome were found in a laboratory stock. These patterns of G-banding are discernable both at mitosis in adults and embryos of both sexes and at all stages of male meiosis. Some regions which are gaps after G-banding appear as dark bands after C-banding. Consequently the supernumerary chromosome is mainly darkly stained with C-banding. In addition the centromeres and some telomeres are C-banded along with narrow interstitial bands and polymorphic heterochromatic blocks.--C-banding was not always successful, the technique often yields a mixture of G- and C-banding. The disparity of banding between the normal complement and the B-chromosome implies that whatever the source of origin of the B it has undergone spectacular changes in organisation since its origin."} {"id": "PMID:1269342", "title": "Haplo-diploid locust embryos arising by accidental thelytoky in Chortoicetes terminifera investigated by G-banding.", "content": "Two mosaic sibling embryos of the Australian plague locust, Chortoicetes terminifera are reported with haploid and diploid cell lines in widely differing proportions. One small chromosome pair involved in the two cases has alternative morphology and a B-chromosome is present in one. In addition, G-banding identifies two medium-sized chromosome pairs and alternative states of a second small pair. Using these markers it is clear that both diploid cell lines are homozygous for the chromosomes of the corresponding haploid line. These embryos have thus developed by accidental parthenogenesis from haploid cells, some of which were duplicated by endomitosis after development began.", "contents": "Haplo-diploid locust embryos arising by accidental thelytoky in Chortoicetes terminifera investigated by G-banding. Two mosaic sibling embryos of the Australian plague locust, Chortoicetes terminifera are reported with haploid and diploid cell lines in widely differing proportions. One small chromosome pair involved in the two cases has alternative morphology and a B-chromosome is present in one. In addition, G-banding identifies two medium-sized chromosome pairs and alternative states of a second small pair. Using these markers it is clear that both diploid cell lines are homozygous for the chromosomes of the corresponding haploid line. These embryos have thus developed by accidental parthenogenesis from haploid cells, some of which were duplicated by endomitosis after development began."} {"id": "PMID:1269343", "title": "Prolongation of replication time after doublings of the DNA content of polytene chromosome bands of Chironomus.", "content": "Using 3H-thymidine autoradiography, labeling frequency of homologous asynapsed chromosome bands of the hybrid of Chironomus th. thummi and Chironomus th. piger has been studied. In a number of these bands the DNA content of the thummi bands if 2, 4, 8 or 16 times as large as that of the homologous piger bands (Keyl, 1965). Those bands of CH. TH. thummi which show one doubling of their DNA content in comparison with the homologous piger bands are also labeled two times more frequently than piger. In contrast to this such a correlation between increase of labeling frequency (i.e. prolongation of replication time) and doubling of the DNA content is not observed, when thummi bands have 4, 8 or 16 times more DNA than their homologues in piger. In these cases replication time is also prolonged after each doubling. Duration of DNA synthesis increases linearly but always by a smaller factor as the corresponding DNA content is increased.", "contents": "Prolongation of replication time after doublings of the DNA content of polytene chromosome bands of Chironomus. Using 3H-thymidine autoradiography, labeling frequency of homologous asynapsed chromosome bands of the hybrid of Chironomus th. thummi and Chironomus th. piger has been studied. In a number of these bands the DNA content of the thummi bands if 2, 4, 8 or 16 times as large as that of the homologous piger bands (Keyl, 1965). Those bands of CH. TH. thummi which show one doubling of their DNA content in comparison with the homologous piger bands are also labeled two times more frequently than piger. In contrast to this such a correlation between increase of labeling frequency (i.e. prolongation of replication time) and doubling of the DNA content is not observed, when thummi bands have 4, 8 or 16 times more DNA than their homologues in piger. In these cases replication time is also prolonged after each doubling. Duration of DNA synthesis increases linearly but always by a smaller factor as the corresponding DNA content is increased."} {"id": "PMID:1269344", "title": "A comparative analysis of the karyotypes of Cricetus cricetus and Cricetulus griseus.", "content": "This study presents a comparison of the mitotic chromosomes of the two species of hamsters Cricetus cricetus (European hamster) and Cricetulus griseus (Chinese hamster), which have the same chromosome number of 2n=22.--G-banding procedure reveals striking similarities in both karyotypes and gives the possibility to analyse structural changes so that two examples for Robertsonian rearrangement can be observed.--A remarkable kind of difference between the two karyotypes becomes obvious after C-banding procedure. While Cricetus cricetus shows a large amount of predominantly centromeric heterochromatin, in Cricetulus griseus C-bands are less conspicuous, and a few chromosomes do not exhibit any centromeric heterochromatin at all.", "contents": "A comparative analysis of the karyotypes of Cricetus cricetus and Cricetulus griseus. This study presents a comparison of the mitotic chromosomes of the two species of hamsters Cricetus cricetus (European hamster) and Cricetulus griseus (Chinese hamster), which have the same chromosome number of 2n=22.--G-banding procedure reveals striking similarities in both karyotypes and gives the possibility to analyse structural changes so that two examples for Robertsonian rearrangement can be observed.--A remarkable kind of difference between the two karyotypes becomes obvious after C-banding procedure. While Cricetus cricetus shows a large amount of predominantly centromeric heterochromatin, in Cricetulus griseus C-bands are less conspicuous, and a few chromosomes do not exhibit any centromeric heterochromatin at all."} {"id": "PMID:1269348", "title": "Anastomotic recurrence after anterior resection for carcinoma: Lahey Clinic experience.", "content": "A retrospective study of 152 patients who underwent anterior resection for carcinoma of the rectum and rectosigmoid from 1963 to 1969 is presented. Eighteen anastomotic recurrences (two benign) were observed. Factors associated with high recurrence rates are discussed, and a scheme for identification of those patients in high-risk groups is presented. The value of this study lies in facilitating decisions involving operative and postoperative management of distal colonic lesions.", "contents": "Anastomotic recurrence after anterior resection for carcinoma: Lahey Clinic experience. A retrospective study of 152 patients who underwent anterior resection for carcinoma of the rectum and rectosigmoid from 1963 to 1969 is presented. Eighteen anastomotic recurrences (two benign) were observed. Factors associated with high recurrence rates are discussed, and a scheme for identification of those patients in high-risk groups is presented. The value of this study lies in facilitating decisions involving operative and postoperative management of distal colonic lesions."} {"id": "PMID:1269350", "title": "Nonsuture colonic anastomosis.", "content": "Methyl-2-cyanoacrylate was used for nonsuture end-to-end anastomosis of the ascending colon in 35 male Sprague-Dawley rats. The results were studied in seven sacrificed rats and eight rats that died after the procedure. The mortality rate was 22 per cent in a six-month period. Twenty animals are being observed for further studies of the anastomoic site and possible late carcinogenic activity of the monomer. The local histotoxicity of methyl-2-cyanoacrylate, the strong binding capacity, the abundance of scar tissue, and the distraction of the mucosa, as pointed out by several earlier investigators, were confirmed in this work. Also, it was strongly evident that the age of the glue has a significant influence on survival. The use of tissue adhesives as a substitute for standard suture technique or as a reinforcement of an inadequate suture line requires further study. Investigations designed for improving properties of these monomers appear warranted.", "contents": "Nonsuture colonic anastomosis. Methyl-2-cyanoacrylate was used for nonsuture end-to-end anastomosis of the ascending colon in 35 male Sprague-Dawley rats. The results were studied in seven sacrificed rats and eight rats that died after the procedure. The mortality rate was 22 per cent in a six-month period. Twenty animals are being observed for further studies of the anastomoic site and possible late carcinogenic activity of the monomer. The local histotoxicity of methyl-2-cyanoacrylate, the strong binding capacity, the abundance of scar tissue, and the distraction of the mucosa, as pointed out by several earlier investigators, were confirmed in this work. Also, it was strongly evident that the age of the glue has a significant influence on survival. The use of tissue adhesives as a substitute for standard suture technique or as a reinforcement of an inadequate suture line requires further study. Investigations designed for improving properties of these monomers appear warranted."} {"id": "PMID:1269351", "title": "Prevention of urinary retention by fluid restriction following anorectal operations.", "content": "In a carefully controlled prospective randomized study of 500 patients, the postoperative catheterization rate following anorectal surgical procedures was dramatically reduced by a combination of severe dehydration of the patients and reorientation of the nursing personnel to delay catheterization until the bladder is distended. The effectiveness of fluid restriction was clearly demonstrated.", "contents": "Prevention of urinary retention by fluid restriction following anorectal operations. In a carefully controlled prospective randomized study of 500 patients, the postoperative catheterization rate following anorectal surgical procedures was dramatically reduced by a combination of severe dehydration of the patients and reorientation of the nursing personnel to delay catheterization until the bladder is distended. The effectiveness of fluid restriction was clearly demonstrated."} {"id": "PMID:1269352", "title": "Drug-induced pseudomembranous enterocolitis: a new etiologic agent.", "content": "Pseudomembranous enterocolitis is an iatrogenic illness resulting from the oral or intramuscular use of broad-spectrum antibiotics. It is characterized by diarrhea, mucosal inflammation, and pseudomembrane formation in the gastrointestinal tract. The diagnosis is established by an index of suspicion in individuals who have been on antibiotic therapy, proctosigmoidoscopic examination, stool smears, cultures, and sensitivity. Treatment should be directed to eliminating the etiologic factor and replacing the physiologic abnormality.", "contents": "Drug-induced pseudomembranous enterocolitis: a new etiologic agent. Pseudomembranous enterocolitis is an iatrogenic illness resulting from the oral or intramuscular use of broad-spectrum antibiotics. It is characterized by diarrhea, mucosal inflammation, and pseudomembrane formation in the gastrointestinal tract. The diagnosis is established by an index of suspicion in individuals who have been on antibiotic therapy, proctosigmoidoscopic examination, stool smears, cultures, and sensitivity. Treatment should be directed to eliminating the etiologic factor and replacing the physiologic abnormality."} {"id": "PMID:1269353", "title": "Scleroderma of the colon with obstruction: report of a case.", "content": "A case of a patient who had colonic obstruction caused by scleroderma is described. The obstruction initially was treated by means of a colostomy, and later subtotal colectomy was carried out. This is the fifth report of a patient with symptomatic colonic scleroderma successfully treated by colonic resection. A review of colonic scleroderma is included.", "contents": "Scleroderma of the colon with obstruction: report of a case. A case of a patient who had colonic obstruction caused by scleroderma is described. The obstruction initially was treated by means of a colostomy, and later subtotal colectomy was carried out. This is the fifth report of a patient with symptomatic colonic scleroderma successfully treated by colonic resection. A review of colonic scleroderma is included."} {"id": "PMID:1269354", "title": "Perianal endometrioma: report of five cases.", "content": "One of the gynecologists' commonest findings at pelvic laparotomy is endometriosis. Despite the fact that the presence of endometrial tissue in ectopic locations is commonplace, the finding of a perianal endometrioma is no more than a surgical curiosity. Very few cases have been reported. The present report describes five such verified cases. Interestingly enough, only two of the five cases were diagnosed preoperatively. The pathogenesis of endometriosis has been, and continues to be, controversial. The prevailing theories include 1) transtubal regurgitation of menstrual blood, 2) the coelomic metaplasia doctrine, 3) lymphatic dissemination, and 4) hematogenous spread. Pathologically the lesions may vary grossly from red-blue to yellowish-brown implants, ranging in size from microscopic to 1-2 cm in diameter. The definitive histologic diagnosis requires two of the following three features-glands, stroma, and hemosiderin pigment. The clinical manifestations depend upon the functional activity of the involved tissue and may range from an asymptomatic mass to the classic presentation of a mass increasing in size and becoming acutely painful during menstruation but subsiding in size and decreasing in tenderness between menstrual periods. These protean manifestations are readily illustrated by the cases presented. Anatomically the lesions are usually found in old episiotomy scars. Because these lesions are usually readily accessible, and because their exact nature is frequently not known preoperatively, the treatment of choice is local excision. Complementary hormonal therapy has been suggested, but the value of such treatment is not yet proven. Ovarian ablative therapy is also considered.", "contents": "Perianal endometrioma: report of five cases. One of the gynecologists' commonest findings at pelvic laparotomy is endometriosis. Despite the fact that the presence of endometrial tissue in ectopic locations is commonplace, the finding of a perianal endometrioma is no more than a surgical curiosity. Very few cases have been reported. The present report describes five such verified cases. Interestingly enough, only two of the five cases were diagnosed preoperatively. The pathogenesis of endometriosis has been, and continues to be, controversial. The prevailing theories include 1) transtubal regurgitation of menstrual blood, 2) the coelomic metaplasia doctrine, 3) lymphatic dissemination, and 4) hematogenous spread. Pathologically the lesions may vary grossly from red-blue to yellowish-brown implants, ranging in size from microscopic to 1-2 cm in diameter. The definitive histologic diagnosis requires two of the following three features-glands, stroma, and hemosiderin pigment. The clinical manifestations depend upon the functional activity of the involved tissue and may range from an asymptomatic mass to the classic presentation of a mass increasing in size and becoming acutely painful during menstruation but subsiding in size and decreasing in tenderness between menstrual periods. These protean manifestations are readily illustrated by the cases presented. Anatomically the lesions are usually found in old episiotomy scars. Because these lesions are usually readily accessible, and because their exact nature is frequently not known preoperatively, the treatment of choice is local excision. Complementary hormonal therapy has been suggested, but the value of such treatment is not yet proven. Ovarian ablative therapy is also considered."} {"id": "PMID:1269355", "title": "Diffuse villous adenomatosis of the colon: report of a case.", "content": "A 62-year-old man had symptons of congestive heart failure precipitated by chronic blood-loss anemia. Barium-enema studies were consistent with diffuse polyposis of the colon. A total colectomy followed by ileoproctostomy was performed. Histologic examination of numerous polyps showed them to represent villous adenomas. Despite diffuse involvement, electrolyte depletion did not occur. Follow up is planned because of the possibility of future villous adenomas in the small bowel.", "contents": "Diffuse villous adenomatosis of the colon: report of a case. A 62-year-old man had symptons of congestive heart failure precipitated by chronic blood-loss anemia. Barium-enema studies were consistent with diffuse polyposis of the colon. A total colectomy followed by ileoproctostomy was performed. Histologic examination of numerous polyps showed them to represent villous adenomas. Despite diffuse involvement, electrolyte depletion did not occur. Follow up is planned because of the possibility of future villous adenomas in the small bowel."} {"id": "PMID:1269358", "title": "Serpiginous (geographic) choroiditis.", "content": "The rare pathological condition of serpiginous choroiditis is discussed on the basis of four observations. The authors discuss the different views advanced in the literature in regard to the aetiology. They advance arguments in favor of an inflammatory pathogenesis. The problems of the differential diagnosis are also considered in some detail.", "contents": "Serpiginous (geographic) choroiditis. The rare pathological condition of serpiginous choroiditis is discussed on the basis of four observations. The authors discuss the different views advanced in the literature in regard to the aetiology. They advance arguments in favor of an inflammatory pathogenesis. The problems of the differential diagnosis are also considered in some detail."} {"id": "PMID:1269365", "title": "Pathogenesis of papilloedema.", "content": "There appear to be 3 factors in the development of papilloedema - an arterial shunt to the prelaminar tissue and a raised venous pressure in the absence of a raised intraocular pressure, which are passive effects, and an overspill of pial autoregulative vasodilatation which is not passive. In addition the arterial shunt may lead to excessive local autoregulative effects. The engorgement of the fine vessels of the prelaminar tissue, the loss of the spontaneous venous pulse on the disc and the venous overfilling are thought to indicate increased supply and blood flow rather than the reverse. The other general causes of papilloedema can also be explained by the autoregulative mechanism or its breakdown as they involve hypercapnia, tissue anoxia or severe hypertension.", "contents": "Pathogenesis of papilloedema. There appear to be 3 factors in the development of papilloedema - an arterial shunt to the prelaminar tissue and a raised venous pressure in the absence of a raised intraocular pressure, which are passive effects, and an overspill of pial autoregulative vasodilatation which is not passive. In addition the arterial shunt may lead to excessive local autoregulative effects. The engorgement of the fine vessels of the prelaminar tissue, the loss of the spontaneous venous pulse on the disc and the venous overfilling are thought to indicate increased supply and blood flow rather than the reverse. The other general causes of papilloedema can also be explained by the autoregulative mechanism or its breakdown as they involve hypercapnia, tissue anoxia or severe hypertension."} {"id": "PMID:1269366", "title": "The essentials of data sources in eye epidemiology.", "content": "The extensive literature on eye epidemiology was selectively reviewed to provide a concise and comprehensive summary on the current status of available data sources. The topics being covered were epidemiologic data evaluation, data handling, card registration, computer analysis, geographic factors, socio-economic conditions, personal attributes, genetic backgrounds, twin analysis and laboratory procedures for host defense factors including humoral and cellular immunity. Also, the scope of this article encompassed such major practical issues as glaucoma, cataract and other blinding diseases as well as traffic and occupational hazards. Epidemiologic information thus obtainable through data searching may prove tobe instrumental in the identification of any potential preventive measures in ophthalmology and public health.", "contents": "The essentials of data sources in eye epidemiology. The extensive literature on eye epidemiology was selectively reviewed to provide a concise and comprehensive summary on the current status of available data sources. The topics being covered were epidemiologic data evaluation, data handling, card registration, computer analysis, geographic factors, socio-economic conditions, personal attributes, genetic backgrounds, twin analysis and laboratory procedures for host defense factors including humoral and cellular immunity. Also, the scope of this article encompassed such major practical issues as glaucoma, cataract and other blinding diseases as well as traffic and occupational hazards. Epidemiologic information thus obtainable through data searching may prove tobe instrumental in the identification of any potential preventive measures in ophthalmology and public health."} {"id": "PMID:1269367", "title": "Sensorial anomalies in strabismus. (suppression, anomalous correspondence, amblyopia).", "content": "Some concepts regarding suppression, anomalous correspondence and amblyopia are revised according to the sensorial findings obtainable from esotropic patients directly in casual seeing (with the aid of the striated glasses test) and by grading a sensorial dissociating effect (with the aid of a bar of optical filters). The following points are emphasized: 1. Suppression appears to be minimal in small angle strabismus where diplopia seems mainly to be avoided by an anomalous correspondence mechanism. On the contrary, suppression is the prevalent mechanism in large angle strabismus. 2. The anomalous correspondence mechanism may lead to a weak type of anomalous binocular vision which is easily interrupted by light optical filters or by dissociating tests. 3. The subjective space of patients with anomalous binocular vision resembles that of normal binocular vision in some aspects. 4. The development of amblyopia is interpreted in the light of these new concepts on suppression and anomalous binocular vision. 5. Postoperatively, anomalous correspondence rapidly re-adapts to the smaller angle deviation and may normalize if the deviation is completely eliminated. This is evident only in casual seeing; for a certain time, dissociating tests reveal the preoperative correspondence status. This behaviour of correspondence in casual seeing has led to attempts at normalizing anomalous correspondence by prism therapy. Newly observed sensotio-motorial obstacles, however, have been found to frequently hamper treatment in casual seeing.", "contents": "Sensorial anomalies in strabismus. (suppression, anomalous correspondence, amblyopia). Some concepts regarding suppression, anomalous correspondence and amblyopia are revised according to the sensorial findings obtainable from esotropic patients directly in casual seeing (with the aid of the striated glasses test) and by grading a sensorial dissociating effect (with the aid of a bar of optical filters). The following points are emphasized: 1. Suppression appears to be minimal in small angle strabismus where diplopia seems mainly to be avoided by an anomalous correspondence mechanism. On the contrary, suppression is the prevalent mechanism in large angle strabismus. 2. The anomalous correspondence mechanism may lead to a weak type of anomalous binocular vision which is easily interrupted by light optical filters or by dissociating tests. 3. The subjective space of patients with anomalous binocular vision resembles that of normal binocular vision in some aspects. 4. The development of amblyopia is interpreted in the light of these new concepts on suppression and anomalous binocular vision. 5. Postoperatively, anomalous correspondence rapidly re-adapts to the smaller angle deviation and may normalize if the deviation is completely eliminated. This is evident only in casual seeing; for a certain time, dissociating tests reveal the preoperative correspondence status. This behaviour of correspondence in casual seeing has led to attempts at normalizing anomalous correspondence by prism therapy. Newly observed sensotio-motorial obstacles, however, have been found to frequently hamper treatment in casual seeing."} {"id": "PMID:1269368", "title": "Experimentally induced variations in the dark adaptation functions of a severe strabismic amblyope.", "content": "Dark adaptation curves were determined for an amblyopic and a normal control subject following a variety of preadaptation conditions. Sizable between-eye differences were found in the dark adaptation functions of only the amblyope; the magnitude of such differences varied with this subject's distance from the light preadapting screen and with the effective size of his pupils during the light preadaptation period. Marked differences were also found between the dark adaptation functions of both eyes of the amblyopic subject and those of the normal subject. The preadaptation-dependent changes in the dark adaptation function of the amblyopic subject are hypothesized to result from anomalies of amblyopic eye light adaptation which are referable to disturbances of retinal receptor alignment.", "contents": "Experimentally induced variations in the dark adaptation functions of a severe strabismic amblyope. Dark adaptation curves were determined for an amblyopic and a normal control subject following a variety of preadaptation conditions. Sizable between-eye differences were found in the dark adaptation functions of only the amblyope; the magnitude of such differences varied with this subject's distance from the light preadapting screen and with the effective size of his pupils during the light preadaptation period. Marked differences were also found between the dark adaptation functions of both eyes of the amblyopic subject and those of the normal subject. The preadaptation-dependent changes in the dark adaptation function of the amblyopic subject are hypothesized to result from anomalies of amblyopic eye light adaptation which are referable to disturbances of retinal receptor alignment."} {"id": "PMID:1269369", "title": "Sensorio-motorial anomalies in strabismus: (anomalous movements).", "content": "The attempts at treating anomalous correspondence by prisms in esotropia have led to the observation that frequently the angle of deviation increases with prismatic correction. The convergent movements induced by base-out prisms in esotropic patients resemble normal fusional movements in some aspects; they are provisorily called 'anomalous movements' and the objective differences between anomalous movements and normal fusional movements are reported. The strength of 'anomalous movements' are investigated with prisms. This with the aim of better understanding this sensorio-motorial sequela of strabismus and possibly selecting those patients who are more apt for prismatic therapy. The main criteria adopted today for eliminating anomalous movements and the residual postoperative deviation related with them are listed. Finally, the way anomalous movements may interfere with surgery is discussed.", "contents": "Sensorio-motorial anomalies in strabismus: (anomalous movements). The attempts at treating anomalous correspondence by prisms in esotropia have led to the observation that frequently the angle of deviation increases with prismatic correction. The convergent movements induced by base-out prisms in esotropic patients resemble normal fusional movements in some aspects; they are provisorily called 'anomalous movements' and the objective differences between anomalous movements and normal fusional movements are reported. The strength of 'anomalous movements' are investigated with prisms. This with the aim of better understanding this sensorio-motorial sequela of strabismus and possibly selecting those patients who are more apt for prismatic therapy. The main criteria adopted today for eliminating anomalous movements and the residual postoperative deviation related with them are listed. Finally, the way anomalous movements may interfere with surgery is discussed."} {"id": "PMID:1269410", "title": "[Muco-serous otitis media- a frequently missed disease of the middle ear (author's transl)].", "content": "Muco-serous otitis media (muco-serotympanon) is one of the most frequent otological diseases not only among children but increasingly also in the adult age group. In addition to microscopic otoscopy tympanometry is most relevant for diagnosis. Tympanometry is based on measurement of acoustic resistance at the level of the tympanic membrane. In cases of muco-serous otitis very characteristic types of tympanometric curves are obtained. Paracenlastic tube through the tympanic membrane are recommended for therapy.", "contents": "[Muco-serous otitis media- a frequently missed disease of the middle ear (author's transl)]. Muco-serous otitis media (muco-serotympanon) is one of the most frequent otological diseases not only among children but increasingly also in the adult age group. In addition to microscopic otoscopy tympanometry is most relevant for diagnosis. Tympanometry is based on measurement of acoustic resistance at the level of the tympanic membrane. In cases of muco-serous otitis very characteristic types of tympanometric curves are obtained. Paracenlastic tube through the tympanic membrane are recommended for therapy."} {"id": "PMID:1269411", "title": "[Prenatal diagnosis of globoid-cell leukodystrophy (Krabbe's disease) (author's transl)].", "content": "Amniocentesis in the 17th week of pregnancy in a 23-year-old woman who had previously lost a child with enzymatically proven Krabbe's disease revealed normal activity in cell-free amniotic fluid. But in two amniotic cell cultures a 25% defect of cerebroside-beta-galactosidase was found. The prenatal diagnosis of Krabbe's disease was subsequently confirmed after abortion of the fetus by enzymatic and morphological examination (globoid cells in the spinal-cord sections).", "contents": "[Prenatal diagnosis of globoid-cell leukodystrophy (Krabbe's disease) (author's transl)]. Amniocentesis in the 17th week of pregnancy in a 23-year-old woman who had previously lost a child with enzymatically proven Krabbe's disease revealed normal activity in cell-free amniotic fluid. But in two amniotic cell cultures a 25% defect of cerebroside-beta-galactosidase was found. The prenatal diagnosis of Krabbe's disease was subsequently confirmed after abortion of the fetus by enzymatic and morphological examination (globoid cells in the spinal-cord sections)."} {"id": "PMID:1269416", "title": "[HL-A histocompatibility antigens in children with coeliac disease (author's transl)].", "content": "HL-A antigens were determined in 41 unrelated coeliac children and in clinically healthy parents and siblings of 40 of these patients using a lymphocyte microcytotoxicity test. 58.5% of the coeliac patients had phenotype HL-A 8 compared with an HL-A 8 frequency of 16.6% in a control group of 320 unrelated individuals (P less than 0.0005). Excluding five patients not of pure German origin HL-A 8 frequency increases to 63.9%. The increase of HL-A 1 frequency in coeliac patients is attributed to linkage disequilibrium between HL-A 8 and HL-A 1. The haplotype HL-A 1.8 frequency was significantly increased in coeliac children (P less than 0.0001) with frequency elevation also in parents (P approximately 0.025) but not in siblings. Furthermore, an increase in frequency of HL-A 12 and a decreased frequency of HL-A 7 and HL-A 9 was found in coeliac patients. Five clinically healthy siblings had the same HL-A haplotypes as their affected sisters and brothers.", "contents": "[HL-A histocompatibility antigens in children with coeliac disease (author's transl)]. HL-A antigens were determined in 41 unrelated coeliac children and in clinically healthy parents and siblings of 40 of these patients using a lymphocyte microcytotoxicity test. 58.5% of the coeliac patients had phenotype HL-A 8 compared with an HL-A 8 frequency of 16.6% in a control group of 320 unrelated individuals (P less than 0.0005). Excluding five patients not of pure German origin HL-A 8 frequency increases to 63.9%. The increase of HL-A 1 frequency in coeliac patients is attributed to linkage disequilibrium between HL-A 8 and HL-A 1. The haplotype HL-A 1.8 frequency was significantly increased in coeliac children (P less than 0.0001) with frequency elevation also in parents (P approximately 0.025) but not in siblings. Furthermore, an increase in frequency of HL-A 12 and a decreased frequency of HL-A 7 and HL-A 9 was found in coeliac patients. Five clinically healthy siblings had the same HL-A haplotypes as their affected sisters and brothers."} {"id": "PMID:1269417", "title": "[Electrocardiographic changes after surgical manipulation of the carotid arteries (author's transl)].", "content": "Seven patients showed deep symmetrical T wave inversions in their electrocardiograms after bilateral carotid endarterectomy. There was no evidence for myocardial ischaemia. These changes reversed completely within three months. Similar disturbances of repolarisation were seen in rats after bilateral denervation of the carotid sinus. These changes are probably of neurogenic origin, like those seen with central nervous system disorders. Their origin seems to be correlated to the acute imbalance of the autonomic innervation of the heart after surgical disturbance of baro- and chemoreceptors.", "contents": "[Electrocardiographic changes after surgical manipulation of the carotid arteries (author's transl)]. Seven patients showed deep symmetrical T wave inversions in their electrocardiograms after bilateral carotid endarterectomy. There was no evidence for myocardial ischaemia. These changes reversed completely within three months. Similar disturbances of repolarisation were seen in rats after bilateral denervation of the carotid sinus. These changes are probably of neurogenic origin, like those seen with central nervous system disorders. Their origin seems to be correlated to the acute imbalance of the autonomic innervation of the heart after surgical disturbance of baro- and chemoreceptors."} {"id": "PMID:1269418", "title": "[Urinary excretion of hydroxyproline in acromegaly (author's transl)].", "content": "Urinary excretion of hydroxyproline was examined with the Hypronosticon test in 25 patients with acromegaly (13 men, 12 women) and 15 healthy persons. At the same time, plasma levels and urinary excretion of phosphorus and calcium were also measured. Patients with active acromegaly had a significantly higher urinary hydroxyproline output (32.55 +/- 8.68 mg/24 h m2) than healthy persons (12.12 +/- 2.33 mg/24 h-m2). They also excreted considerably more hydroxyproline than patients with successfully treated acromegaly. Effective treatment was proved by STH levels and good suppressibility by 100 mg glucose. Unsucessfully treated patients, on the contrary, had a raised urinary excretion of hydroxyproline (31.23 +/- 16.61 mg/24 h-m2) and high fasting plasma levels of somatotropic hormone. Hydroxyprolinuria proved, therefore, of value in assessing the development and treatment of acromegaly.", "contents": "[Urinary excretion of hydroxyproline in acromegaly (author's transl)]. Urinary excretion of hydroxyproline was examined with the Hypronosticon test in 25 patients with acromegaly (13 men, 12 women) and 15 healthy persons. At the same time, plasma levels and urinary excretion of phosphorus and calcium were also measured. Patients with active acromegaly had a significantly higher urinary hydroxyproline output (32.55 +/- 8.68 mg/24 h m2) than healthy persons (12.12 +/- 2.33 mg/24 h-m2). They also excreted considerably more hydroxyproline than patients with successfully treated acromegaly. Effective treatment was proved by STH levels and good suppressibility by 100 mg glucose. Unsucessfully treated patients, on the contrary, had a raised urinary excretion of hydroxyproline (31.23 +/- 16.61 mg/24 h-m2) and high fasting plasma levels of somatotropic hormone. Hydroxyprolinuria proved, therefore, of value in assessing the development and treatment of acromegaly."} {"id": "PMID:1269428", "title": "[Treatment of cardiogenic shock after acute myocardial infarction with intra-aortic balloon counterpulsation (author's transl)].", "content": "Intra-aortic balloon counterpulsation (IABP) was used in 20 patients with acute myocardial infarction and cardiogenic shock, after four hours of drug treatment. In all instances the abnormal haemodynamic state had been demonstrated. Four patients were successfully treated and finally discharged home. In two with post-infarction ventricular septal defect and cardiogenic shock, IABP also successfully reversed the shock state, while in seven the shock state was reversed but they died 2-8 days after IABP had been stopped. IABP failed in seven patients who died during its application. In those in whom IABP failed there had been no significant fall in pulmonary-artery pressure and no significant increase in stroke volume. The post-mortem examinations demonstrated that cardiogenic shock was irreversible where more than 50% of the left ventricular myocardium had been infarcted.", "contents": "[Treatment of cardiogenic shock after acute myocardial infarction with intra-aortic balloon counterpulsation (author's transl)]. Intra-aortic balloon counterpulsation (IABP) was used in 20 patients with acute myocardial infarction and cardiogenic shock, after four hours of drug treatment. In all instances the abnormal haemodynamic state had been demonstrated. Four patients were successfully treated and finally discharged home. In two with post-infarction ventricular septal defect and cardiogenic shock, IABP also successfully reversed the shock state, while in seven the shock state was reversed but they died 2-8 days after IABP had been stopped. IABP failed in seven patients who died during its application. In those in whom IABP failed there had been no significant fall in pulmonary-artery pressure and no significant increase in stroke volume. The post-mortem examinations demonstrated that cardiogenic shock was irreversible where more than 50% of the left ventricular myocardium had been infarcted."} {"id": "PMID:1269429", "title": "[Prazosin--a new antihypertensive agent (author's transl)].", "content": "40 patients with essential hypertension of varying degrees were treated with prazosin for up to 6 months. Both in severe (n=10) and in moderately severe (n=28) hypertension a significant decrease of the systolic and diastolic blood pressure was observed after only one month of treatment. This effect was even more evident after 3 and 6 months. 18 patiets showed orthostatic disorders at the beginning of treatment which in all cases disappeared after several weeks. No side effects were observed which could be attributed with certainty to prazosin.", "contents": "[Prazosin--a new antihypertensive agent (author's transl)]. 40 patients with essential hypertension of varying degrees were treated with prazosin for up to 6 months. Both in severe (n=10) and in moderately severe (n=28) hypertension a significant decrease of the systolic and diastolic blood pressure was observed after only one month of treatment. This effect was even more evident after 3 and 6 months. 18 patiets showed orthostatic disorders at the beginning of treatment which in all cases disappeared after several weeks. No side effects were observed which could be attributed with certainty to prazosin."} {"id": "PMID:1269430", "title": "[Clinical use of NPH insulin (author's transl)].", "content": "NPH Insulin-Retard Leo has an even action spread over about 20 hours. Despite this long duration of action, single daily injections proved to be adequate in only 9-12% of diabetic patients. Twice daily injection provided a highly favourable fasting blood sugar level in all instances. Because of the small initial effect, the addition of regular insulin proved necessary in some of the patients. 50:50 mixture of regular and NPH Insulin-Retard Leo is available as Insulin Initard Leo, a 30:70 mixture as Insulin Semitard Leo. There remains a group of diabetics who should mix them to their own individual requirements. There were no local reactions when using highly purified components, as long as it was the first time that the patients used such insulin or were changed over from other reaction-free preparations. Diabetics with cutaneous allergies due to other forms of insulin had the same response to NPH preparations as to highly purified insulins of other forms.", "contents": "[Clinical use of NPH insulin (author's transl)]. NPH Insulin-Retard Leo has an even action spread over about 20 hours. Despite this long duration of action, single daily injections proved to be adequate in only 9-12% of diabetic patients. Twice daily injection provided a highly favourable fasting blood sugar level in all instances. Because of the small initial effect, the addition of regular insulin proved necessary in some of the patients. 50:50 mixture of regular and NPH Insulin-Retard Leo is available as Insulin Initard Leo, a 30:70 mixture as Insulin Semitard Leo. There remains a group of diabetics who should mix them to their own individual requirements. There were no local reactions when using highly purified components, as long as it was the first time that the patients used such insulin or were changed over from other reaction-free preparations. Diabetics with cutaneous allergies due to other forms of insulin had the same response to NPH preparations as to highly purified insulins of other forms."} {"id": "PMID:1269431", "title": "[Treatment of metastasising melanoma with a combination of cytostatic agents (author's transl)].", "content": "In a prospective phase-II study of 16 patients with melanoma in stage III, the influence of a combination of cytostatic drugs on tumour growth was studied. All patients had extensive metastases in soft tissues, intestines and, some of them, in bone. The treatment consisted of brief infusions of 2 mg vincristine, 200 mg carmustine and 600 mg dacarbazine per m2 body surface for six days, repeated at seven week intervals up to six times. Two of the 16 patients had complete and two had partial remission, while two remained in status quo for four and five months, respectively. In the remaining ten patients the combined therapy had no influence on the progression of the disease: the more extensive the tumour spread and the worse the general condition of the patient, the less successful was the treatment.", "contents": "[Treatment of metastasising melanoma with a combination of cytostatic agents (author's transl)]. In a prospective phase-II study of 16 patients with melanoma in stage III, the influence of a combination of cytostatic drugs on tumour growth was studied. All patients had extensive metastases in soft tissues, intestines and, some of them, in bone. The treatment consisted of brief infusions of 2 mg vincristine, 200 mg carmustine and 600 mg dacarbazine per m2 body surface for six days, repeated at seven week intervals up to six times. Two of the 16 patients had complete and two had partial remission, while two remained in status quo for four and five months, respectively. In the remaining ten patients the combined therapy had no influence on the progression of the disease: the more extensive the tumour spread and the worse the general condition of the patient, the less successful was the treatment."} {"id": "PMID:1269432", "title": "[Lowering of pulmonary-arterial pressure with nitroprusside in mitral stenosis and cor pulmonale (author's transl)].", "content": "Nitroprusside was infused intravenously (20, 40, 80 and 200 mug/min) in nine patients with pulmonary hypertension due to mitral stenosis (group I), nine with precapillary pulmonary hypertension associated with primary lung disease (group II) and nine with normal pulmonary-arterial pressures (group III). The mean pulmonary-arterial pressure was markedly reduced at a rate of 20 mug/min in group I and II, while higher doses were necessary in group III to produce a similar effect. Mean arterial pressure was decreased in all three groups and was dose-related. Heart rate rose, stroke volume fell during nitroprusside administration, while cardiac output remained unchanged. Pulmonary vascular resistance was reduced on 20 mug/min in group I, but only on 200 mug/min or more in group II, and unchanged at all dosages in group III. Peripheral vascular resistance declined in all three groups on nitroprusside infusion, which is apparently of value in the short-term lowering of pulmonary hypertension.", "contents": "[Lowering of pulmonary-arterial pressure with nitroprusside in mitral stenosis and cor pulmonale (author's transl)]. Nitroprusside was infused intravenously (20, 40, 80 and 200 mug/min) in nine patients with pulmonary hypertension due to mitral stenosis (group I), nine with precapillary pulmonary hypertension associated with primary lung disease (group II) and nine with normal pulmonary-arterial pressures (group III). The mean pulmonary-arterial pressure was markedly reduced at a rate of 20 mug/min in group I and II, while higher doses were necessary in group III to produce a similar effect. Mean arterial pressure was decreased in all three groups and was dose-related. Heart rate rose, stroke volume fell during nitroprusside administration, while cardiac output remained unchanged. Pulmonary vascular resistance was reduced on 20 mug/min in group I, but only on 200 mug/min or more in group II, and unchanged at all dosages in group III. Peripheral vascular resistance declined in all three groups on nitroprusside infusion, which is apparently of value in the short-term lowering of pulmonary hypertension."} {"id": "PMID:1269433", "title": "[Congenital saccharase-isomaltase deficiency: a six-year survey (author's transl)].", "content": "Saccharase-isomaltase deficiency was discovered in five children. The diagnosis was made on the basis of an abnormal oral saccharose loading response and demonstrating decreased activity of intestinal saccharase and isomaltase in the presence of normal small-intestinal mucosa. Three children failed to thrive, and all had recurrent diarrhoea. The diagnosis was made in children aged six to twenty-two months. Treatment consisted of saccharose-free diet or feeding with an enzyme preparation, Bi-Myconase. Saccharose-containing foods were increasingly tolerated beyond the second year of life so that children aged 2 1/2 to 3 1/4 years no longer required special treatment.", "contents": "[Congenital saccharase-isomaltase deficiency: a six-year survey (author's transl)]. Saccharase-isomaltase deficiency was discovered in five children. The diagnosis was made on the basis of an abnormal oral saccharose loading response and demonstrating decreased activity of intestinal saccharase and isomaltase in the presence of normal small-intestinal mucosa. Three children failed to thrive, and all had recurrent diarrhoea. The diagnosis was made in children aged six to twenty-two months. Treatment consisted of saccharose-free diet or feeding with an enzyme preparation, Bi-Myconase. Saccharose-containing foods were increasingly tolerated beyond the second year of life so that children aged 2 1/2 to 3 1/4 years no longer required special treatment."} {"id": "PMID:1269454", "title": "[Middle-level medical training in Cuba].", "content": "The background, evolution, and prospects for training middle-level medical technicians in Cuba are reviewed, with emphasis on the relationships existing among socioeconomic structures, the education sector, and the health sector. Developments since the revolution of 1959 may be divided into three periods--1959-1964, 1965-1969, and 1970-1975--which reflect a clear policy progressing from the quantitative to the qualitative. A description is given of the health and education systems and subsystems that have emerged as a result of changes in the social, political, and economic system and have made it possible to develop new approaches to teaching, including work-study programs and integrated training.", "contents": "[Middle-level medical training in Cuba]. The background, evolution, and prospects for training middle-level medical technicians in Cuba are reviewed, with emphasis on the relationships existing among socioeconomic structures, the education sector, and the health sector. Developments since the revolution of 1959 may be divided into three periods--1959-1964, 1965-1969, and 1970-1975--which reflect a clear policy progressing from the quantitative to the qualitative. A description is given of the health and education systems and subsystems that have emerged as a result of changes in the social, political, and economic system and have made it possible to develop new approaches to teaching, including work-study programs and integrated training."} {"id": "PMID:1269455", "title": "[The planning of higher or university education and the concept of politics, strategy and planning].", "content": "The phenomenon of mass education and the crisis of university education in Latin America, in particular in the 1960's, are broadly analyzed. From the facts that characterized the period in question, two conclusions may be drawn: (1) that the basic role of the university must be redefined on the basis of new principles and different content; and (2) that a university must be administered by a system other than improvization. The concepts of policy, strategy, and plan are considered in depth and then explained as they apply to curriculum planning and design.", "contents": "[The planning of higher or university education and the concept of politics, strategy and planning]. The phenomenon of mass education and the crisis of university education in Latin America, in particular in the 1960's, are broadly analyzed. From the facts that characterized the period in question, two conclusions may be drawn: (1) that the basic role of the university must be redefined on the basis of new principles and different content; and (2) that a university must be administered by a system other than improvization. The concepts of policy, strategy, and plan are considered in depth and then explained as they apply to curriculum planning and design."} {"id": "PMID:1269456", "title": "[Considerations on the admission policy for the medical school of the university of Costa Rica].", "content": "A study conducted by the University of Costa Rica examined the ratio between the total national population and the number of physicians, as well as the variations that might occur in this ratio depending on population growth, annual number of graduates from the School, incorporation of foreign medical graduates, and deaths in the physician population. The purpose of the investigation was to give the school sufficient information to formulate admissions policy that would take into account the needs of national health programs and the demand for medical care services.", "contents": "[Considerations on the admission policy for the medical school of the university of Costa Rica]. A study conducted by the University of Costa Rica examined the ratio between the total national population and the number of physicians, as well as the variations that might occur in this ratio depending on population growth, annual number of graduates from the School, incorporation of foreign medical graduates, and deaths in the physician population. The purpose of the investigation was to give the school sufficient information to formulate admissions policy that would take into account the needs of national health programs and the demand for medical care services."} {"id": "PMID:1269457", "title": "[Activities and strategy of an office or department of medical education].", "content": "About eight years ago medical education offices or departments began to be established in the medical and health sciences schools in Latin America. These units have endeavored to solve the problem common to so many of the schools of lack of coordination in activities related to the planning of the various aspects of the teaching/learning process. Many of them have succeeded in doing so and have also been able to interest the university community in the continuing evaluation and improvement of curriculum. The main activities of a medical education office are summarized: educational development (assistance in defining objectives, curriculum organization, teaching methodology, evaluation systems, training of and pedagogical assistance to faculty members); investigation of the factors that enter into the teaching/learning process; and preparation of teaching material and bibliographic information. Clearly the activities of the medical education office or department must be coordinated with those of all the sectors in the school, and it must be open to proposals and suggestions from the entire community.", "contents": "[Activities and strategy of an office or department of medical education]. About eight years ago medical education offices or departments began to be established in the medical and health sciences schools in Latin America. These units have endeavored to solve the problem common to so many of the schools of lack of coordination in activities related to the planning of the various aspects of the teaching/learning process. Many of them have succeeded in doing so and have also been able to interest the university community in the continuing evaluation and improvement of curriculum. The main activities of a medical education office are summarized: educational development (assistance in defining objectives, curriculum organization, teaching methodology, evaluation systems, training of and pedagogical assistance to faculty members); investigation of the factors that enter into the teaching/learning process; and preparation of teaching material and bibliographic information. Clearly the activities of the medical education office or department must be coordinated with those of all the sectors in the school, and it must be open to proposals and suggestions from the entire community."} {"id": "PMID:1269458", "title": "[Population studies of Gm (a)].", "content": "The author carried out her own studies of Gm (a) on 2816 persons, in whom a factor frequency was found in 33.3% and gene frequency--0.1833. She summarized all published in Bulgaria up to now population studies in respect to Gm (a) (1838), in whom the mean factor frequency was 38.67% and gene frequency--0.2129. The theoretical probability for excluding fatherhood only by Gm (a) in our country was 10.23%.", "contents": "[Population studies of Gm (a)]. The author carried out her own studies of Gm (a) on 2816 persons, in whom a factor frequency was found in 33.3% and gene frequency--0.1833. She summarized all published in Bulgaria up to now population studies in respect to Gm (a) (1838), in whom the mean factor frequency was 38.67% and gene frequency--0.2129. The theoretical probability for excluding fatherhood only by Gm (a) in our country was 10.23%."} {"id": "PMID:1269459", "title": "[Histomorphological changes in the lymphoid and internal organs of adult guinea pigs in anaphylactic shock, induced 8 months after thymectomy].", "content": "Anaphylactic shock was induced in adult guinea pigs eight months after operative thymectomy. It was established that thymectomy caused depletion of lymphoid tissue with atrophy of lymphyc follicles and disappearence of germinative centers in the spleen, mesenterial lymph gland and intestinal lymph tissue. There was no anaphyactic shock in 81.2% of the thymectomized animals as a result of the inhibited immunoallergic reactivity, but dystrophic and inflammatory changes in their parenchymatous organs were more frequent and graver in comparison with the nonthymectomized animals.", "contents": "[Histomorphological changes in the lymphoid and internal organs of adult guinea pigs in anaphylactic shock, induced 8 months after thymectomy]. Anaphylactic shock was induced in adult guinea pigs eight months after operative thymectomy. It was established that thymectomy caused depletion of lymphoid tissue with atrophy of lymphyc follicles and disappearence of germinative centers in the spleen, mesenterial lymph gland and intestinal lymph tissue. There was no anaphyactic shock in 81.2% of the thymectomized animals as a result of the inhibited immunoallergic reactivity, but dystrophic and inflammatory changes in their parenchymatous organs were more frequent and graver in comparison with the nonthymectomized animals."} {"id": "PMID:1269460", "title": "[Total protein and serum protein fractions in atherosclerotic animals treated with a protein hydrolysate].", "content": "The changes in the metabolism of oranism of animals with experimental atherosclerosis show not only disturbances in the lipid, but early changes in the protein metabolism as well. The author examined total protein and serum protein fractions of 61 male guinea pigs with a weight of 350 to 500 gm. There was marked disproteinemia reduction of albumin and an increase of globulins in the animals with experimental atherosclerosis (which received a diet with 0.3% of cholesterol of the food, disolved in 25% of cow butter for a period of 140 days)...", "contents": "[Total protein and serum protein fractions in atherosclerotic animals treated with a protein hydrolysate]. The changes in the metabolism of oranism of animals with experimental atherosclerosis show not only disturbances in the lipid, but early changes in the protein metabolism as well. The author examined total protein and serum protein fractions of 61 male guinea pigs with a weight of 350 to 500 gm. There was marked disproteinemia reduction of albumin and an increase of globulins in the animals with experimental atherosclerosis (which received a diet with 0.3% of cholesterol of the food, disolved in 25% of cow butter for a period of 140 days)..."} {"id": "PMID:1269462", "title": "[Effect of adepren on the behavior and brain catecholamines of rats in an open field setup].", "content": "The authors carried out experimental studies with the Bulgarian preparat on Adepren on the behaviour of rats in open field procedure together with parallel electroencephalographic studies and examined the changes in the content of cerebral catecholamines during acute and chronic administration. The preparation after single application had depresive effect on both components of the motor activity: horisontal and vertical. The horizontal component of the motor activity surpassed the norm with almost 20% at the end of the experimental period after chronic administration. There was desynchronizing effect in the KEG recordings. Adepren after acute and chronic application elevated significantly the level of noradrenaline and dopamine in the brain. The obtained results gave a foundation to the authors to suggest that the examined preparation and maoinhibiting effect.", "contents": "[Effect of adepren on the behavior and brain catecholamines of rats in an open field setup]. The authors carried out experimental studies with the Bulgarian preparat on Adepren on the behaviour of rats in open field procedure together with parallel electroencephalographic studies and examined the changes in the content of cerebral catecholamines during acute and chronic administration. The preparation after single application had depresive effect on both components of the motor activity: horisontal and vertical. The horizontal component of the motor activity surpassed the norm with almost 20% at the end of the experimental period after chronic administration. There was desynchronizing effect in the KEG recordings. Adepren after acute and chronic application elevated significantly the level of noradrenaline and dopamine in the brain. The obtained results gave a foundation to the authors to suggest that the examined preparation and maoinhibiting effect."} {"id": "PMID:1269463", "title": "[Electrophysiological aspects in the mechanism of action of some psychotropic drug agents].", "content": "On the basis of the experiments on animals the author made an attempt to find out the place of the action of some psychotropic drugs on the central nervous system and to discover the changes, which occurred in the functional state of various cerebral structures. He used drugs Imupramine (Psychoforin) and Diazepan (Valium), administered localy in some structures of the lymbic system and reticular formation of the cat cerebrum, using stereotaxic technique. The evaluation of the occurred changes was made by the changes in the spontaneous and induced cerebral activity, using the method of double stimuli. The obtained results gave foundation to state that drugs with antidepresive action (Imipramin) inhibited amigdalic complex and the structures connected with it, but benzodiazepines (Diazepam) revealed this action also on the mesencephalic reticular formation as the structures, brocked by the antidepresants, were not affected. In conclusion an electrophysilogic argumentation was made for the combined application of both groups of preparations in neurotic patients.", "contents": "[Electrophysiological aspects in the mechanism of action of some psychotropic drug agents]. On the basis of the experiments on animals the author made an attempt to find out the place of the action of some psychotropic drugs on the central nervous system and to discover the changes, which occurred in the functional state of various cerebral structures. He used drugs Imupramine (Psychoforin) and Diazepan (Valium), administered localy in some structures of the lymbic system and reticular formation of the cat cerebrum, using stereotaxic technique. The evaluation of the occurred changes was made by the changes in the spontaneous and induced cerebral activity, using the method of double stimuli. The obtained results gave foundation to state that drugs with antidepresive action (Imipramin) inhibited amigdalic complex and the structures connected with it, but benzodiazepines (Diazepam) revealed this action also on the mesencephalic reticular formation as the structures, brocked by the antidepresants, were not affected. In conclusion an electrophysilogic argumentation was made for the combined application of both groups of preparations in neurotic patients."} {"id": "PMID:1269464", "title": "[Role of calcium ions in the contractile effects of acetylcholine (experiments on the guinea pig vas deferens)].", "content": "The authors carried out experiments on isolated vasa deferentia, obtained from a guinea pig. Recordings of the isotonic contractile activity was made by means of a strain gauge. Ink records were made on graduated tape of miliampermeter Tesla. Acethylcholine was used in a concentration of 1 X 10(-5) M, but serotonine-in a concentration of 1 X 10(-5) M. Growing reduction of the values was observed very regularly in all experiments both in the serotonine and acethylcholine contractions of vas deferens after diminution of the content of calcium in the Krebs solution from 0,9 to 0,15 mM. Gradual recovery of the value of the spastic effects of the examined substances was observed after placing the isolated organ in Krebs solution with a normal content of calcium. In analogous role of calcium in the spastic effects of the two mediators there were also some differences in the dynamics on which this role was manifested. The authors discussed the significance of the external calcium for the realization of the contractile effects of acethylcholine and serotonine on vas deferens of a guinea pig.", "contents": "[Role of calcium ions in the contractile effects of acetylcholine (experiments on the guinea pig vas deferens)]. The authors carried out experiments on isolated vasa deferentia, obtained from a guinea pig. Recordings of the isotonic contractile activity was made by means of a strain gauge. Ink records were made on graduated tape of miliampermeter Tesla. Acethylcholine was used in a concentration of 1 X 10(-5) M, but serotonine-in a concentration of 1 X 10(-5) M. Growing reduction of the values was observed very regularly in all experiments both in the serotonine and acethylcholine contractions of vas deferens after diminution of the content of calcium in the Krebs solution from 0,9 to 0,15 mM. Gradual recovery of the value of the spastic effects of the examined substances was observed after placing the isolated organ in Krebs solution with a normal content of calcium. In analogous role of calcium in the spastic effects of the two mediators there were also some differences in the dynamics on which this role was manifested. The authors discussed the significance of the external calcium for the realization of the contractile effects of acethylcholine and serotonine on vas deferens of a guinea pig."} {"id": "PMID:1269465", "title": "[Normal excretion of corticosteroid hormones in rat urine studied by a thin-layer chromatographic method].", "content": "The author examined the parameters of normal excretion of cortico steroid hormones and their metabolites in urine of rats (11 single fractions) by the method of a thin-layer chromatography. The data could be accepted as norms of corticosteroid excretion in urine of young adult rats of the strain Wistar. Nine biological important indices e-corticosteroids in urine of normal rats were described. He discussed the physiological pecofliarities of the normal excretion of corticosteroid hormones and genetical and/or nongenutical factors, determining corticosteroid formula in urine of the rat. He indicated the significance of a thin-layer chromatography for the determination of corticosteroid excretioi-for the evaluation of the functional state of the adrenal cortex and liver under various experimental conditions.", "contents": "[Normal excretion of corticosteroid hormones in rat urine studied by a thin-layer chromatographic method]. The author examined the parameters of normal excretion of cortico steroid hormones and their metabolites in urine of rats (11 single fractions) by the method of a thin-layer chromatography. The data could be accepted as norms of corticosteroid excretion in urine of young adult rats of the strain Wistar. Nine biological important indices e-corticosteroids in urine of normal rats were described. He discussed the physiological pecofliarities of the normal excretion of corticosteroid hormones and genetical and/or nongenutical factors, determining corticosteroid formula in urine of the rat. He indicated the significance of a thin-layer chromatography for the determination of corticosteroid excretioi-for the evaluation of the functional state of the adrenal cortex and liver under various experimental conditions."} {"id": "PMID:1269485", "title": "Seizure disorders in offspring of parents with a history of seizures - a maternal-paternal difference?", "content": "If the patterns of seizure disorders in parents and offspring could be assessed accurately, some insight might be gained into the relative role of genetic and environmental factors in the development of convulsive disorders. In this study 908 children born in a Rochester, Minnesota hospital from 1922 through 1972 whose mother or father had a verified and classified diagnosis of seizure have been followed from birth for evidence of any convulsive episode or seizure disorder. The observed numbers of various types of convulsions in the offspring are compared to the expected the number based on local age-specific incidence rates. The outstanding finding was that a higher than expected number of children whose mothers had epilepsy also suffered from seizures (epilepsy or febrile convulsions), whereas no such increase was detected among the children of affected fathers.", "contents": "Seizure disorders in offspring of parents with a history of seizures - a maternal-paternal difference? If the patterns of seizure disorders in parents and offspring could be assessed accurately, some insight might be gained into the relative role of genetic and environmental factors in the development of convulsive disorders. In this study 908 children born in a Rochester, Minnesota hospital from 1922 through 1972 whose mother or father had a verified and classified diagnosis of seizure have been followed from birth for evidence of any convulsive episode or seizure disorder. The observed numbers of various types of convulsions in the offspring are compared to the expected the number based on local age-specific incidence rates. The outstanding finding was that a higher than expected number of children whose mothers had epilepsy also suffered from seizures (epilepsy or febrile convulsions), whereas no such increase was detected among the children of affected fathers."} {"id": "PMID:1269486", "title": "Neuropsychological correlates of the electroencephalogram in epileptics: II. The waking posterior rhythm and its interaction with epileptiform activity.", "content": "Relationships between psychological functions and waking dominant posterior rhythm frequency (DPRF) of the EEG were evaluated with and without simultaneous evaluation of epileptiform discharges. Ninety adult epileptics with uncontrolled seizure disorders treated solely by diphenylhydantoin underwent EEGs during wakefulness and administrations of an extensive battery of neuropsychological tests. The DPRF was particularly related to abilities simultaneously requiring attention an complex mental manipulations. Rhythms slower than 7.5-8.0 Hz were accompanied by relatively poorer performance than rhythms which were faster. When epileptiform discharges were considered in combination with the DPRF, larger differences in abilities were demonstrated, and the psycholoigcal correlates tended to be more substantial for the epileptiform discharge variable than for the DPRF variable. The selection of tests employed and the range of rhythms assessed are critical to these findings, and the substantial construction of these variables by many previous investigators is believed to be related to the negative findings often reported.", "contents": "Neuropsychological correlates of the electroencephalogram in epileptics: II. The waking posterior rhythm and its interaction with epileptiform activity. Relationships between psychological functions and waking dominant posterior rhythm frequency (DPRF) of the EEG were evaluated with and without simultaneous evaluation of epileptiform discharges. Ninety adult epileptics with uncontrolled seizure disorders treated solely by diphenylhydantoin underwent EEGs during wakefulness and administrations of an extensive battery of neuropsychological tests. The DPRF was particularly related to abilities simultaneously requiring attention an complex mental manipulations. Rhythms slower than 7.5-8.0 Hz were accompanied by relatively poorer performance than rhythms which were faster. When epileptiform discharges were considered in combination with the DPRF, larger differences in abilities were demonstrated, and the psycholoigcal correlates tended to be more substantial for the epileptiform discharge variable than for the DPRF variable. The selection of tests employed and the range of rhythms assessed are critical to these findings, and the substantial construction of these variables by many previous investigators is believed to be related to the negative findings often reported."} {"id": "PMID:1269487", "title": "Ischemic heart disease in patients with epilepsy.", "content": "It has been suggested that patients with epilepsy and particularly those on long-term anticonvulsant medication may have a lower than expected risk of ischemic heart disease. The records of a cohort of patients with epilepsy in Rochester, Minnesota were reviewed to ascertain their rates of occurrence of ischemic heart disease. The results did not show any relative decrease in the incidence or mortality rates due to ischemic heart disease among men or women with epilepsy. The numbers of ischemic heart disease incidence and mortality cases were 25 and 15, respectively, relative to corresponding expected values of 15.0 and 15.7 new and fatal events. The use of anticonvulsant medications did not appear to influence the rates of ischemic heart disease among the patients with epilepsy. Subgroups of the epilepsy patients, by etiology and types of epilepsy, were not found to account for a disproportionate share of the ischemic heart disease. The survivorship of epilepsy patients after the initial manifestations of ischemic heart disease was comparable to that expected among all ischemic heart disease patients.", "contents": "Ischemic heart disease in patients with epilepsy. It has been suggested that patients with epilepsy and particularly those on long-term anticonvulsant medication may have a lower than expected risk of ischemic heart disease. The records of a cohort of patients with epilepsy in Rochester, Minnesota were reviewed to ascertain their rates of occurrence of ischemic heart disease. The results did not show any relative decrease in the incidence or mortality rates due to ischemic heart disease among men or women with epilepsy. The numbers of ischemic heart disease incidence and mortality cases were 25 and 15, respectively, relative to corresponding expected values of 15.0 and 15.7 new and fatal events. The use of anticonvulsant medications did not appear to influence the rates of ischemic heart disease among the patients with epilepsy. Subgroups of the epilepsy patients, by etiology and types of epilepsy, were not found to account for a disproportionate share of the ischemic heart disease. The survivorship of epilepsy patients after the initial manifestations of ischemic heart disease was comparable to that expected among all ischemic heart disease patients."} {"id": "PMID:1269488", "title": "Ketamine hydrochloride and its effect on a chronic cobalt epileptic cortical focus.", "content": "The effects of anesthetic and nonanesthetic doses of ketamine hydrochloride were studied in male adult rats in which a primary and a projected epileptic focus were induced with implantation of cobalt in the right or left frontal cortex. Electrical activity was recorded from the frontal, parietal, and occipital cortices. Nonanesthetic doses of ketamine were associated with activation or enhancement of primary and projected focal electrical activity, as well as turning behavior toward the side of the cobalt focus. Anesthetic doses of ketamine also enhanced or activated the primary and projected foci. These animals demonstrated turning behavior toward the side of the cobalt focus prior to and following the cataleptoid state. During catalepsy, forelimb twitching and oscillating movements of the vibrissae occurred. The activation of primary and projected foci by ketamine at anesthetic and nonanesthetic doses supports the clinical findings that ketamine is epileptogenic in certain patients with a seizure disorder.", "contents": "Ketamine hydrochloride and its effect on a chronic cobalt epileptic cortical focus. The effects of anesthetic and nonanesthetic doses of ketamine hydrochloride were studied in male adult rats in which a primary and a projected epileptic focus were induced with implantation of cobalt in the right or left frontal cortex. Electrical activity was recorded from the frontal, parietal, and occipital cortices. Nonanesthetic doses of ketamine were associated with activation or enhancement of primary and projected focal electrical activity, as well as turning behavior toward the side of the cobalt focus. Anesthetic doses of ketamine also enhanced or activated the primary and projected foci. These animals demonstrated turning behavior toward the side of the cobalt focus prior to and following the cataleptoid state. During catalepsy, forelimb twitching and oscillating movements of the vibrissae occurred. The activation of primary and projected foci by ketamine at anesthetic and nonanesthetic doses supports the clinical findings that ketamine is epileptogenic in certain patients with a seizure disorder."} {"id": "PMID:1269489", "title": "Convulsive fits in thyrotoxicosis.", "content": "A patient with hyperthyroidism is described who developed grand mal seizures when anth-thyroid medication was withdrawn. Pyramidal signs were also present. The EEG reverted to normal and the clinical signs and symptoms disappeared when his thyroid status was again controlled.", "contents": "Convulsive fits in thyrotoxicosis. A patient with hyperthyroidism is described who developed grand mal seizures when anth-thyroid medication was withdrawn. Pyramidal signs were also present. The EEG reverted to normal and the clinical signs and symptoms disappeared when his thyroid status was again controlled."} {"id": "PMID:1269492", "title": "Serum concentration of carbamazepine: comparison of Herrmann's spectrophotometric method and a new GLC method for the determination of carbamazepine.", "content": "A specific direct gas chromatographic method to determine carbamazepine and, semiquantitatively, 10,11-epoxy carbamazepine in serum is described. The average recovery of carbamazepine is 98%, and the error on duplicate determination is +/- 4%. The method is compared with Herrmann's classic spectrophotometric method. In material of 103 patients the mean serum concentration of carbamazepine was 25.5 +/- 12.8 mumoles/1 with GLC and 23.0 +/- 12.6 mumoles/1 with spectrophotometry. The difference was highly significant. The blood sample volume is one-tenth of that needed in spectrophotometry.", "contents": "Serum concentration of carbamazepine: comparison of Herrmann's spectrophotometric method and a new GLC method for the determination of carbamazepine. A specific direct gas chromatographic method to determine carbamazepine and, semiquantitatively, 10,11-epoxy carbamazepine in serum is described. The average recovery of carbamazepine is 98%, and the error on duplicate determination is +/- 4%. The method is compared with Herrmann's classic spectrophotometric method. In material of 103 patients the mean serum concentration of carbamazepine was 25.5 +/- 12.8 mumoles/1 with GLC and 23.0 +/- 12.6 mumoles/1 with spectrophotometry. The difference was highly significant. The blood sample volume is one-tenth of that needed in spectrophotometry."} {"id": "PMID:1269494", "title": "Changes in biochemical and physiological indices in animals produced by the combined effect of benz [a] pyrene and phenol.", "content": "Early energy changes in lungs, liver, and kidneys during the introduction of a benz a pyrene and phenol (as the possible carcinogen activator) were studied. It was observed that 10 days after a single instance introduction of 5 mg benz a pyrene per 0.9% NaCl (60 rats), oxidative phosphorylation in the lungs and livers is disturbed in the test rats, accompanied by a reduction of adenine nucleotides in these tissues. It is assumed that at this stage, the detoxication of benz a pyrene is intensified by free oxidation systems and by the respiratory chain of mitochondria. A chronic 3-month exposure to benz a pyrene and phenol (150 rats, each 5 mg of benz a pyrene per month intratracheally and 0.4 mg/m3 of phenol round-the-clock) results in greater disturbances of the energy exchange in the lungs, liver and kidneys. Benz a pyrene and phenol, individually and in combination, inhibit oxidative phosphorylation in the lungs. This significantly decreases the content of adenine nucleotides in this tissue. Activation of anaerobic glycolysis (twofold) and of aerobic glycolysis (eightfold) does not make up for the energy insufficiency in the tissue. The effect of benz a pyrene and phenol in the liver also results in suppressing oxidative phosphorylation and in the activation of glycolysis (anaerobic 2.5 times, the aerobic 3.7 times). Changes in the bioenergy of the kidneys are not as great. Phenol in its combined effect with benz[a]pyrene intensifies the effect of the latter, as shown primarily to the greater activation of anaerobic and aerobic glycolysis in the lungs and livers of test rats. The observed disturbances as concern the weight dynamics of the animals (weight loss in test rats), vitamin metabolism (their decrease in the organs in in urine) and hemopoiesis of red blood cells (erythropenia) attest to the toxic effect of benz a pyrene phenol on the organism, which is greater in the case of the combined action of the studied agents. No changes were discerned in the morphology of white blood cells.", "contents": "Changes in biochemical and physiological indices in animals produced by the combined effect of benz [a] pyrene and phenol. Early energy changes in lungs, liver, and kidneys during the introduction of a benz a pyrene and phenol (as the possible carcinogen activator) were studied. It was observed that 10 days after a single instance introduction of 5 mg benz a pyrene per 0.9% NaCl (60 rats), oxidative phosphorylation in the lungs and livers is disturbed in the test rats, accompanied by a reduction of adenine nucleotides in these tissues. It is assumed that at this stage, the detoxication of benz a pyrene is intensified by free oxidation systems and by the respiratory chain of mitochondria. A chronic 3-month exposure to benz a pyrene and phenol (150 rats, each 5 mg of benz a pyrene per month intratracheally and 0.4 mg/m3 of phenol round-the-clock) results in greater disturbances of the energy exchange in the lungs, liver and kidneys. Benz a pyrene and phenol, individually and in combination, inhibit oxidative phosphorylation in the lungs. This significantly decreases the content of adenine nucleotides in this tissue. Activation of anaerobic glycolysis (twofold) and of aerobic glycolysis (eightfold) does not make up for the energy insufficiency in the tissue. The effect of benz a pyrene and phenol in the liver also results in suppressing oxidative phosphorylation and in the activation of glycolysis (anaerobic 2.5 times, the aerobic 3.7 times). Changes in the bioenergy of the kidneys are not as great. Phenol in its combined effect with benz[a]pyrene intensifies the effect of the latter, as shown primarily to the greater activation of anaerobic and aerobic glycolysis in the lungs and livers of test rats. The observed disturbances as concern the weight dynamics of the animals (weight loss in test rats), vitamin metabolism (their decrease in the organs in in urine) and hemopoiesis of red blood cells (erythropenia) attest to the toxic effect of benz a pyrene phenol on the organism, which is greater in the case of the combined action of the studied agents. No changes were discerned in the morphology of white blood cells."} {"id": "PMID:1269495", "title": "Combined exposure to ozone and nitrogen dioxide.", "content": "The combined effects of ozone and nitrogen dioxide were assessed in an in vitro test system utilizing human red cells. In general, these two pollutants had additive effects on the parameters measured which included osmotic fragility, acetylcholinesterase activity, lipid peroxidation, reduced glutathione and methemoglobin levels. However, at lower pollutant doses a synergistic increase in lipid peroxides was noted while at higher doses the effect became less than additive. Further studies of this observation suggested that ferrous hemoglobin potentiates ozone-induced lipid peroxidation while methemoglobin, resulting primarily from nitrogen dioxide, inhibits this process. Ozone was also found to potentiate the methemoglobinemic effects of nitrogen dioxide, particularly in sequential studies in which ozone exposure preceded nitrogen dioxide. Inasmuch as the effects of these two pollutants vary from protective to synergistic depending on the pollutant concentration, duration and sequence of exposure, as well as on the parameter assayed, it would appear that the approach to in vivo study of the combined effects of ozone and nitrogen dioxide should be aimed at simulating ambient conditions as closely as possible.", "contents": "Combined exposure to ozone and nitrogen dioxide. The combined effects of ozone and nitrogen dioxide were assessed in an in vitro test system utilizing human red cells. In general, these two pollutants had additive effects on the parameters measured which included osmotic fragility, acetylcholinesterase activity, lipid peroxidation, reduced glutathione and methemoglobin levels. However, at lower pollutant doses a synergistic increase in lipid peroxides was noted while at higher doses the effect became less than additive. Further studies of this observation suggested that ferrous hemoglobin potentiates ozone-induced lipid peroxidation while methemoglobin, resulting primarily from nitrogen dioxide, inhibits this process. Ozone was also found to potentiate the methemoglobinemic effects of nitrogen dioxide, particularly in sequential studies in which ozone exposure preceded nitrogen dioxide. Inasmuch as the effects of these two pollutants vary from protective to synergistic depending on the pollutant concentration, duration and sequence of exposure, as well as on the parameter assayed, it would appear that the approach to in vivo study of the combined effects of ozone and nitrogen dioxide should be aimed at simulating ambient conditions as closely as possible."} {"id": "PMID:1269496", "title": "Time--dose response for nitrogen dioxide exposure in an infectivity model system.", "content": "The concentration of NO2 in polluted atmosphere is subject to wide variation, according to peak traffic load, industrial productivity, intensity of sunlight and meteorological conditions. Normally NO2 has a low basal concentration with superimposed spikes when the above conditions are optimal for its production. Thus, it is important to determine the relative importance of a short-term, relatively high concentration of NO2 versus exposure for longer periods of minimal dose levels. This problem was approached experimentally by measuring the effect of NO2 on an animal's resistance to the induction of bacterial pneumonia. The data collected indicate that: (1) in short-term dose-response studies using the same Ct (concentration x time) product of 7, the actual concentration exerts a greater influence on NO2 effect than does the duration of exposure; (2) when concentration is held constant and the time increased, the average difference in mortality from controls can be seen after only 1 hr exposure to 3.5 ppm and after 3 weeks of exposure to 0.5 ppm; and (3) the relative mean survival time at 3.5 ppm for 1 hr was 18--36 hr less than that of the control animals.", "contents": "Time--dose response for nitrogen dioxide exposure in an infectivity model system. The concentration of NO2 in polluted atmosphere is subject to wide variation, according to peak traffic load, industrial productivity, intensity of sunlight and meteorological conditions. Normally NO2 has a low basal concentration with superimposed spikes when the above conditions are optimal for its production. Thus, it is important to determine the relative importance of a short-term, relatively high concentration of NO2 versus exposure for longer periods of minimal dose levels. This problem was approached experimentally by measuring the effect of NO2 on an animal's resistance to the induction of bacterial pneumonia. The data collected indicate that: (1) in short-term dose-response studies using the same Ct (concentration x time) product of 7, the actual concentration exerts a greater influence on NO2 effect than does the duration of exposure; (2) when concentration is held constant and the time increased, the average difference in mortality from controls can be seen after only 1 hr exposure to 3.5 ppm and after 3 weeks of exposure to 0.5 ppm; and (3) the relative mean survival time at 3.5 ppm for 1 hr was 18--36 hr less than that of the control animals."} {"id": "PMID:1269497", "title": "Methodological approaches to the study of the combined effect of atmospheric pollutants as illustrated by chlorinated hydrocarbons.", "content": "The combined effect of substances with a unidirectional toxic action was studied with the use of several chlorinated hydrocarbons, including 1,2-dichloropropane, 1,2,3-trichloropropane, and perchlorethylene at various concentrations. The results of the study can be used as the basis for the development of methodological approaches to the study of the combined action of toxic substances administered by inhalation. The research plan also incorporated the problem of explaining the nature of the action of the mixture of the test compounds in acute, subacute, and chronic animal experiments. All of the studies were conducted with each compound alone and then in various combinations by using the concentration--time relationship, since a correct evaluation of the combined action of compounds can be obtained by comparing these with the effects observed for the action of each component alone. A graphic representation was obtained of the onset time for a given effect (loss of righting reflex for 50% of the animals) as a function of the active concentrations for the short-term effect of high concentrations of 1,2-dichloropropane, 1,2,3-trichloropropane, and perchloroethylene based on the concentration--time relationship. The nature of the combined action of various combinations (two and three substances) with respect to concentration was studied by using these graphs. At high concentrations, the action of various combinations of the studied substances is additive. An inverse relationship was discovered in subacute experiments between the inactive concentrations and the onset time for changes in the vital activity indices of an organism: the lower the concentration, the later the changes. Additional data were obtained as the result of morphofunctional studies on the toxic properties of the studied compounds, on damage reactions and on adaptational changes. This is of interest from the point of view of explaining the mechanism of action at various concentrations.", "contents": "Methodological approaches to the study of the combined effect of atmospheric pollutants as illustrated by chlorinated hydrocarbons. The combined effect of substances with a unidirectional toxic action was studied with the use of several chlorinated hydrocarbons, including 1,2-dichloropropane, 1,2,3-trichloropropane, and perchlorethylene at various concentrations. The results of the study can be used as the basis for the development of methodological approaches to the study of the combined action of toxic substances administered by inhalation. The research plan also incorporated the problem of explaining the nature of the action of the mixture of the test compounds in acute, subacute, and chronic animal experiments. All of the studies were conducted with each compound alone and then in various combinations by using the concentration--time relationship, since a correct evaluation of the combined action of compounds can be obtained by comparing these with the effects observed for the action of each component alone. A graphic representation was obtained of the onset time for a given effect (loss of righting reflex for 50% of the animals) as a function of the active concentrations for the short-term effect of high concentrations of 1,2-dichloropropane, 1,2,3-trichloropropane, and perchloroethylene based on the concentration--time relationship. The nature of the combined action of various combinations (two and three substances) with respect to concentration was studied by using these graphs. At high concentrations, the action of various combinations of the studied substances is additive. An inverse relationship was discovered in subacute experiments between the inactive concentrations and the onset time for changes in the vital activity indices of an organism: the lower the concentration, the later the changes. Additional data were obtained as the result of morphofunctional studies on the toxic properties of the studied compounds, on damage reactions and on adaptational changes. This is of interest from the point of view of explaining the mechanism of action at various concentrations."} {"id": "PMID:1269498", "title": "Effects of toxaphene on hepatic enzyme induction and circulating steroid levels in the rat.", "content": "Rats were given a single dose of toxaphene (120 mg/kg, equivalent to 1/2 LD50) and sacrificed at 1, 5, and 15 days. Liver weight and hepatic microsomal enzyme activity were increased at day 5 and 15. The level of plasma testosterone was significantly decreased at day 15. In a second experiment rats were given 2.4 mg/kg daily and sacrificed at 1, 3 and 6 months. Liver weight and microsomal enzyme activity were significantly increased over controls; enzyme activity was, however, decreasing by the end of the experiment. Plasma testosterone levels were not affected. It is concluded that enhanced hepatic enzyme induction causes only a transient drop in circulating testosterone levels followed by a return to normal values.", "contents": "Effects of toxaphene on hepatic enzyme induction and circulating steroid levels in the rat. Rats were given a single dose of toxaphene (120 mg/kg, equivalent to 1/2 LD50) and sacrificed at 1, 5, and 15 days. Liver weight and hepatic microsomal enzyme activity were increased at day 5 and 15. The level of plasma testosterone was significantly decreased at day 15. In a second experiment rats were given 2.4 mg/kg daily and sacrificed at 1, 3 and 6 months. Liver weight and microsomal enzyme activity were significantly increased over controls; enzyme activity was, however, decreasing by the end of the experiment. Plasma testosterone levels were not affected. It is concluded that enhanced hepatic enzyme induction causes only a transient drop in circulating testosterone levels followed by a return to normal values."} {"id": "PMID:1269499", "title": "Experimental study of the effect of a series of phosphoroorganic pesticides (Dipterex and Imidan) on embryogenesis.", "content": "Experiments conducted on pregnant Wistar rats show that chlorophos (Dipterex) has embroyotoxic and teratogenic effects after oral introduction in a 80 mg/kg dose during a critical period of embryogenesis. Embryotoxic and teratogenic effects are absent during the introduction of 8 mg/kg of the pesticide. The oral introduction of phthalophos (Imidan) in a 30 mg/kg dose once on day 9 of pregnancy and the introduction of a 1.5 mg/kg dose daily throughout the course of pregnancy caused increased postimplantation mortality of embryos. A dose of 30 mg/kg of phthalophos on day 9 or day 13 of pregnancy causes developmental abnormalities, including hyponathia and hydrocephaly. A 0.06 mg/kg phthalophos dose does not affect the course of embryogenesis in white rats. Thus the organophosphate pesticides Dipterex and Imidan exhibit embryotoxic and teratogenic effects at doses which significantly exceed the acutal amounts of the pesticide that can enter the human organism.", "contents": "Experimental study of the effect of a series of phosphoroorganic pesticides (Dipterex and Imidan) on embryogenesis. Experiments conducted on pregnant Wistar rats show that chlorophos (Dipterex) has embroyotoxic and teratogenic effects after oral introduction in a 80 mg/kg dose during a critical period of embryogenesis. Embryotoxic and teratogenic effects are absent during the introduction of 8 mg/kg of the pesticide. The oral introduction of phthalophos (Imidan) in a 30 mg/kg dose once on day 9 of pregnancy and the introduction of a 1.5 mg/kg dose daily throughout the course of pregnancy caused increased postimplantation mortality of embryos. A dose of 30 mg/kg of phthalophos on day 9 or day 13 of pregnancy causes developmental abnormalities, including hyponathia and hydrocephaly. A 0.06 mg/kg phthalophos dose does not affect the course of embryogenesis in white rats. Thus the organophosphate pesticides Dipterex and Imidan exhibit embryotoxic and teratogenic effects at doses which significantly exceed the acutal amounts of the pesticide that can enter the human organism."} {"id": "PMID:1269500", "title": "Effect of chlorocamphene on the isoenzyme spectrum of lactate dehydrogenase in rat serum and liver.", "content": "Rats were used to study the general activity and the isoenzyme spectrum of lactate dehydrogenase (LDH) during single-instance and long-term introduction of polychlorocamphene. Total lactate dehydrogenase activity decreases in the liver during the single-instance introduction of half the LD50 (120 mg/kg). The isoenzyme spectrum of LDH is characterized by an increase in the quantity of LDH1, LDH2, and LDH3 and by a decrease in the amount of LDH4. The overall LDH activity does not change in blood serum. The isoform ratio changes insignificantly and LDH1 falls, but normalized 15 days after the introduction of the compound. Long-term introduction of polychlorocamphene at levels 1/100 the LD50 dose over 1.3 and 6 months causes a reduction in the overall LDH activity, both in the liver and in the serum. A decrease in the activity of the basic LDH isoenzyme of the liver (LDH5) and a sharp increase in LDH3 are characteristic for the isoenzyme spectrum of the liver. LDH1 and LDH4 decrease and LDH2 and LDH3 increase in blood serum. Beginning with the third month of polychlorocamphene introduction, LDH1 tends to return to normal levels. LDH2, LDH3, and LDH4 do return to normal levels, while LDH5 increases regularly. This results in a reduction of the number of H subunits and an increase of M subunits. This is characteristic of hypoxic states. On comparing the changes in the LDH enzymes of the liver and blood serum, it can be considered that the introduction of polychlorocamphene does not result in an increase in the permeability of the cellular membranes of the liver for LDH isoenzymes, while the observed isoenzyme spectrum shifts in blood serum are either the result of the biosynthesis of the isoforms of this enzyme changed by the compound or the result of the permeability for them of cells of other tissues.", "contents": "Effect of chlorocamphene on the isoenzyme spectrum of lactate dehydrogenase in rat serum and liver. Rats were used to study the general activity and the isoenzyme spectrum of lactate dehydrogenase (LDH) during single-instance and long-term introduction of polychlorocamphene. Total lactate dehydrogenase activity decreases in the liver during the single-instance introduction of half the LD50 (120 mg/kg). The isoenzyme spectrum of LDH is characterized by an increase in the quantity of LDH1, LDH2, and LDH3 and by a decrease in the amount of LDH4. The overall LDH activity does not change in blood serum. The isoform ratio changes insignificantly and LDH1 falls, but normalized 15 days after the introduction of the compound. Long-term introduction of polychlorocamphene at levels 1/100 the LD50 dose over 1.3 and 6 months causes a reduction in the overall LDH activity, both in the liver and in the serum. A decrease in the activity of the basic LDH isoenzyme of the liver (LDH5) and a sharp increase in LDH3 are characteristic for the isoenzyme spectrum of the liver. LDH1 and LDH4 decrease and LDH2 and LDH3 increase in blood serum. Beginning with the third month of polychlorocamphene introduction, LDH1 tends to return to normal levels. LDH2, LDH3, and LDH4 do return to normal levels, while LDH5 increases regularly. This results in a reduction of the number of H subunits and an increase of M subunits. This is characteristic of hypoxic states. On comparing the changes in the LDH enzymes of the liver and blood serum, it can be considered that the introduction of polychlorocamphene does not result in an increase in the permeability of the cellular membranes of the liver for LDH isoenzymes, while the observed isoenzyme spectrum shifts in blood serum are either the result of the biosynthesis of the isoforms of this enzyme changed by the compound or the result of the permeability for them of cells of other tissues."} {"id": "PMID:1269501", "title": "Methods for detecting teratogenic agents in man.", "content": "At a multidiscipline international meeting sponsored by L'Institut de la Vie held at Guadeloupe in January 1974, current methods for detecting teratogenic agents were outlined and discussed. Recommendations of the participants of the conference were: recognize the limitations of the present defenses against teratogenic agents; educate the public and medical profession about the known human teratogenic agents; select for animal teratogenicity screening among new and existing agents by emphasizing substances to which the entire population will be exposed, agents to which pregnant women are exposed, viruses which are found to persist in the human fetus, and agents which have become suspect from clinical experience; recognize that nearly all compounds have a fetotoxic dose but that this does not imply teratogenicity; encourage the development of new, quick in vitro testing methods for detecting teratogenic agents; monitor for sudden increases in the frequency of specific malformations in newborn infants and in aborted fetuses; assure that expert multidiscipline committees are available to evaluate the threat when suspected teratogens are reported; improve teratology information storage and retrieval systems by record linkage of clinical data, linkage between computer systems, and universal identifier system for chemical compounds and congenical malformations; foster the exchange of data, particularly those held by the pharmaceutical industry.", "contents": "Methods for detecting teratogenic agents in man. At a multidiscipline international meeting sponsored by L'Institut de la Vie held at Guadeloupe in January 1974, current methods for detecting teratogenic agents were outlined and discussed. Recommendations of the participants of the conference were: recognize the limitations of the present defenses against teratogenic agents; educate the public and medical profession about the known human teratogenic agents; select for animal teratogenicity screening among new and existing agents by emphasizing substances to which the entire population will be exposed, agents to which pregnant women are exposed, viruses which are found to persist in the human fetus, and agents which have become suspect from clinical experience; recognize that nearly all compounds have a fetotoxic dose but that this does not imply teratogenicity; encourage the development of new, quick in vitro testing methods for detecting teratogenic agents; monitor for sudden increases in the frequency of specific malformations in newborn infants and in aborted fetuses; assure that expert multidiscipline committees are available to evaluate the threat when suspected teratogens are reported; improve teratology information storage and retrieval systems by record linkage of clinical data, linkage between computer systems, and universal identifier system for chemical compounds and congenical malformations; foster the exchange of data, particularly those held by the pharmaceutical industry."} {"id": "PMID:1269502", "title": "Concentration--time relationship for various regimens of inhalation of organic compounds.", "content": "An attempt was made to establish a concentration--time relationship for continuous and interrupted inhalation of a number of nonelectrolytes to establish norms for the permissible content of harmful substances in atmospheric air. The tests showed that the indicated relationship can be expressed in the form of a straight line on a logarithmic grid by using either acute toxicity parameters or the onset of physiological and biochemical shifts. This makes it possible to predict the chronic effect thresholds of substances on the basis of the results of short-term experiments.", "contents": "Concentration--time relationship for various regimens of inhalation of organic compounds. An attempt was made to establish a concentration--time relationship for continuous and interrupted inhalation of a number of nonelectrolytes to establish norms for the permissible content of harmful substances in atmospheric air. The tests showed that the indicated relationship can be expressed in the form of a straight line on a logarithmic grid by using either acute toxicity parameters or the onset of physiological and biochemical shifts. This makes it possible to predict the chronic effect thresholds of substances on the basis of the results of short-term experiments."} {"id": "PMID:1269503", "title": "Chemical structure and properties of selected benzene compounds in relation to biological activity.", "content": "Four fundamental physical parameters of series of benzene derivatives were studied to ascertain correlations with biological activity. These included octanol/water coefficient, vapor pressure, infrared absorption (out-of-plane C-H vibration), and the pi values. Each physicochemical constant exhibited a partial correlation with biological activity suggesting that each played a role. It was presumed that more precise and specific data on the biological activity would have permitted a better correlation. It is postulated that the biological activity of a compound is due to the sum of such physicochemical factors as: partition coefficient, molecular geometry and spatial orientation, electronic characteristics of the molecular orbitals, and vibrational-rotational frequencies of constituent groups.", "contents": "Chemical structure and properties of selected benzene compounds in relation to biological activity. Four fundamental physical parameters of series of benzene derivatives were studied to ascertain correlations with biological activity. These included octanol/water coefficient, vapor pressure, infrared absorption (out-of-plane C-H vibration), and the pi values. Each physicochemical constant exhibited a partial correlation with biological activity suggesting that each played a role. It was presumed that more precise and specific data on the biological activity would have permitted a better correlation. It is postulated that the biological activity of a compound is due to the sum of such physicochemical factors as: partition coefficient, molecular geometry and spatial orientation, electronic characteristics of the molecular orbitals, and vibrational-rotational frequencies of constituent groups."} {"id": "PMID:1269504", "title": "Predicting biological effect as a function of the chemical structure and the primary physical and chemical properties of organic compounds.", "content": "The dependence of biological parameters on chemical structure was studied for a series of compounds with similar chemical structures. Computational formulas were developed on the basis of correlation and regression analysis. These formulas make it possible to predict the biological effect thresholds for a great number of organic compounds on the basis of their primary physical and chemical properties.", "contents": "Predicting biological effect as a function of the chemical structure and the primary physical and chemical properties of organic compounds. The dependence of biological parameters on chemical structure was studied for a series of compounds with similar chemical structures. Computational formulas were developed on the basis of correlation and regression analysis. These formulas make it possible to predict the biological effect thresholds for a great number of organic compounds on the basis of their primary physical and chemical properties."} {"id": "PMID:1269505", "title": "Studies in the behavioral toxicology of environmental contaminants.", "content": "Behavioral toxicology represents a relatively new research area in the West, and a new source of information pertinent to standard setting. Despite this abbreviated history, however, it can call on a rather advanced technology, largely provided by the rapid and extensive development of behavioral pharmacology during the past two decades. As exemplified by the U.S. contribution to the joint study of carbon disulfide, the approach derived from this background relies on the acquisition of dose--effect data with a preparation yielding stable baseline performance. The first study in this collaborative series employed pigeons trained to peck a response device consisting of a transilluminnated plastic disk. Various relationships between this response and the occasions on which it led to the delivery of food were explored in order to ascertain which behavioral variables were most sensitive to acute exposures. In addition, a central nervous system drug, whose neurochemical mode of action is believed to parallel that of carbon disulfide, was tested in the same preparations. Further research on these questions is being continued with monkeys.", "contents": "Studies in the behavioral toxicology of environmental contaminants. Behavioral toxicology represents a relatively new research area in the West, and a new source of information pertinent to standard setting. Despite this abbreviated history, however, it can call on a rather advanced technology, largely provided by the rapid and extensive development of behavioral pharmacology during the past two decades. As exemplified by the U.S. contribution to the joint study of carbon disulfide, the approach derived from this background relies on the acquisition of dose--effect data with a preparation yielding stable baseline performance. The first study in this collaborative series employed pigeons trained to peck a response device consisting of a transilluminnated plastic disk. Various relationships between this response and the occasions on which it led to the delivery of food were explored in order to ascertain which behavioral variables were most sensitive to acute exposures. In addition, a central nervous system drug, whose neurochemical mode of action is believed to parallel that of carbon disulfide, was tested in the same preparations. Further research on these questions is being continued with monkeys."} {"id": "PMID:1269506", "title": "Investigation of the mechanism of action of atmospheric pollutants on the central nervous system and comparative evaluation of methods of study.", "content": "Some aspects of the mechanism of action of atmospheric pollutants (acetone, benzene, ammonia, formaldehyde, and ozone) on the central nervous system were studied by using methods of functional electroencephalography (analysis of the readjustment reaction to a rhythmic light stimulus, evoked potentials of the cerebral cortex, and determination of the photometrazol thresholds). Effects of the compounds were determined for the various structures of the cerebral cortex of experimental animals. The most sensitive structures were those which were first to associate in the reaction to toxic agents (the corticomedial nucleus of the amygdaloid complex and the olfactory bulb). EEG indices were observed which were indicative of an adverse effect (epileptoid activity in the most sensitive formations of the brain and a stable generalized stress rhythm in the neocortex and in the limbic ascending reticular system). During long-term action of toxic materials at low concentrations, changes were observed in the parameters of the primary and secondary responses of the visual evoked potential which were indicative of a disturbance of the cortical inhibition processes. This can be considered one effect of atmospheric pollutants at low concentrations. Problems of the comparative sensitivity of the various methods of studying the central nervous system are being investigated with a single compound: carbon bisulfide. In human experiments concerned with the fine coordination of measured movements such as writing and the solution of arithmetic problems, the subject-operator observed that repeated inhalation of subsensory concentrations of carbon bisulfide (0.08 mg/m3 level) disturbs the rate of execution of assigned motor processes. In tests with rats with developed instrument conditioned reflexes, it was shown that entire behavioral acts deteriorate under the effect of the same carbon bisulfide concentration. In tests on rabbits, simultaneous neurophysiological and neurochemical analyses were performed on the changes in the functional state of the central nervous system under chronic exposure to carbon bisulfide at various concentrations.", "contents": "Investigation of the mechanism of action of atmospheric pollutants on the central nervous system and comparative evaluation of methods of study. Some aspects of the mechanism of action of atmospheric pollutants (acetone, benzene, ammonia, formaldehyde, and ozone) on the central nervous system were studied by using methods of functional electroencephalography (analysis of the readjustment reaction to a rhythmic light stimulus, evoked potentials of the cerebral cortex, and determination of the photometrazol thresholds). Effects of the compounds were determined for the various structures of the cerebral cortex of experimental animals. The most sensitive structures were those which were first to associate in the reaction to toxic agents (the corticomedial nucleus of the amygdaloid complex and the olfactory bulb). EEG indices were observed which were indicative of an adverse effect (epileptoid activity in the most sensitive formations of the brain and a stable generalized stress rhythm in the neocortex and in the limbic ascending reticular system). During long-term action of toxic materials at low concentrations, changes were observed in the parameters of the primary and secondary responses of the visual evoked potential which were indicative of a disturbance of the cortical inhibition processes. This can be considered one effect of atmospheric pollutants at low concentrations. Problems of the comparative sensitivity of the various methods of studying the central nervous system are being investigated with a single compound: carbon bisulfide. In human experiments concerned with the fine coordination of measured movements such as writing and the solution of arithmetic problems, the subject-operator observed that repeated inhalation of subsensory concentrations of carbon bisulfide (0.08 mg/m3 level) disturbs the rate of execution of assigned motor processes. In tests with rats with developed instrument conditioned reflexes, it was shown that entire behavioral acts deteriorate under the effect of the same carbon bisulfide concentration. In tests on rabbits, simultaneous neurophysiological and neurochemical analyses were performed on the changes in the functional state of the central nervous system under chronic exposure to carbon bisulfide at various concentrations."} {"id": "PMID:1269508", "title": "Methods to assess reproductive effects of environmental chemicals: studies of cadmium and boron administered orally.", "content": "Results of a U.S.S.R.--U.S. cooperative laboratory effort to improve and validate experimental techniques used to assess subtle reproductive effects in male laboratory animals are reported. The present studies attempted to evaluate the reproductive toxicity of cadmium as cadmium chloride and boron as borax (Na2B4O7) and to investigate the mechanism of toxicity in the rat following acute and subchronic oral exposure. In vitro cell separation techniques, in vivo serial mating tests, and plasma assays for hormones were utilized. Effects on the seminal vesicle and prostate were evaluated with chemical and enzyme assays. Clinical chemistry was monitored routinely. Acute oral doses, expressed as boron were 45, 150, and 450 mg/kg while doses for cadmium equivalent were 6.25, 12.5, and 25 mg/kg. Rats were also allowed free access to drinking water containing either boron (0.3, 1.0, and 6.0 mg/l.) or cadmium (0.001, and 0.l mg/l.) for 90 days. Randomly selected animals were studied following 30, 60, and 90 days of treatment. These initial studies, utilizing a variety of methods to assess the reproductive toxicity of environmental substances in male animals, suggest that cadmium and boron at the concentrations and dose regimens tested are without significant reproductive toxicity.", "contents": "Methods to assess reproductive effects of environmental chemicals: studies of cadmium and boron administered orally. Results of a U.S.S.R.--U.S. cooperative laboratory effort to improve and validate experimental techniques used to assess subtle reproductive effects in male laboratory animals are reported. The present studies attempted to evaluate the reproductive toxicity of cadmium as cadmium chloride and boron as borax (Na2B4O7) and to investigate the mechanism of toxicity in the rat following acute and subchronic oral exposure. In vitro cell separation techniques, in vivo serial mating tests, and plasma assays for hormones were utilized. Effects on the seminal vesicle and prostate were evaluated with chemical and enzyme assays. Clinical chemistry was monitored routinely. Acute oral doses, expressed as boron were 45, 150, and 450 mg/kg while doses for cadmium equivalent were 6.25, 12.5, and 25 mg/kg. Rats were also allowed free access to drinking water containing either boron (0.3, 1.0, and 6.0 mg/l.) or cadmium (0.001, and 0.l mg/l.) for 90 days. Randomly selected animals were studied following 30, 60, and 90 days of treatment. These initial studies, utilizing a variety of methods to assess the reproductive toxicity of environmental substances in male animals, suggest that cadmium and boron at the concentrations and dose regimens tested are without significant reproductive toxicity."} {"id": "PMID:1269509", "title": "Toxic and gonadotropic effects of cadmium and boron relative to standards for these substances in drinking water.", "content": "Experimental research was conducted on the study of the relationship of the general toxic and gonadotoxic effects of cadmium and boron under conditions of subacute and chronic oral intoxication on white random-bred rats, by use of biochemical, physiological, cytological, and pathomorphological methods. It is shown that the gonadotoxic effect of cadmium is manifested on the same level (3 mg/kg of body weight) as the general toxic effect. The gonadotoxic effect of boron is dominant and is manifested at a lower level (6 mg/kg of body weight) than the general toxic effect (20 mg/kg). On the basis of the results of chronic experiments, 0.001 mg/l. is recommended as the hygienic standard for cadmium in water and 0.5 mg/l. for boron.", "contents": "Toxic and gonadotropic effects of cadmium and boron relative to standards for these substances in drinking water. Experimental research was conducted on the study of the relationship of the general toxic and gonadotoxic effects of cadmium and boron under conditions of subacute and chronic oral intoxication on white random-bred rats, by use of biochemical, physiological, cytological, and pathomorphological methods. It is shown that the gonadotoxic effect of cadmium is manifested on the same level (3 mg/kg of body weight) as the general toxic effect. The gonadotoxic effect of boron is dominant and is manifested at a lower level (6 mg/kg of body weight) than the general toxic effect (20 mg/kg). On the basis of the results of chronic experiments, 0.001 mg/l. is recommended as the hygienic standard for cadmium in water and 0.5 mg/l. for boron."} {"id": "PMID:1269510", "title": "Physicochemical properties of some organophosphates in relation to their chronic toxicity.", "content": "Organophosphates in increasing amounts and wider varieties of molecular structure are being used to replace the organochlorine pesticides. It has been assumed that the organophosphates as a class would have a minimal chronic toxicity due to rapid hydrolysis and an unfavorable partitioning as regards to lipids. The physicochemical properties of a number of representative organophosphates were determined, including the octanol/water partition coeffecient, hydrolysis, and binding to proteins. Those having a halogenated aryl substitution were found to have partition coefficients not largely different from the organochlorines, suggesting the possibility of fat deposition. Certain of these compounds are sufficiently stable toward hydrolysis to allow bioaccumulation to occur. These preliminary findings appear to indicate a correlation between readily determined physical properties and the potential for chronic effects in this class of compounds.", "contents": "Physicochemical properties of some organophosphates in relation to their chronic toxicity. Organophosphates in increasing amounts and wider varieties of molecular structure are being used to replace the organochlorine pesticides. It has been assumed that the organophosphates as a class would have a minimal chronic toxicity due to rapid hydrolysis and an unfavorable partitioning as regards to lipids. The physicochemical properties of a number of representative organophosphates were determined, including the octanol/water partition coeffecient, hydrolysis, and binding to proteins. Those having a halogenated aryl substitution were found to have partition coefficients not largely different from the organochlorines, suggesting the possibility of fat deposition. Certain of these compounds are sufficiently stable toward hydrolysis to allow bioaccumulation to occur. These preliminary findings appear to indicate a correlation between readily determined physical properties and the potential for chronic effects in this class of compounds."} {"id": "PMID:1269511", "title": "Methods for predicting chronic toxicity parameters of substances in the area of water hygiene.", "content": "The development of rapid methods for determining chronic toxicity parameters of chemical compounds introduced by the oral route into an organism with water was studied. Formulas are verified with which threshold values and no-effect toxicity doses for substances can be obtained on the basis of various toxicologic parameters. For the example of organophosphates, a methodological scheme was developed for conducting an accelerated experiment for predicting the chronic toxicity of low and average cumulative compounds. Results are presented indicating the inadvisability of using lower animals as test subjects with the aim of predicting toxicity for higher animals. It is pointed out that patterns of homology and isomerism are observed in the comparison of chronic intoxication threshold doses as well as in acute toxicity values of substances.", "contents": "Methods for predicting chronic toxicity parameters of substances in the area of water hygiene. The development of rapid methods for determining chronic toxicity parameters of chemical compounds introduced by the oral route into an organism with water was studied. Formulas are verified with which threshold values and no-effect toxicity doses for substances can be obtained on the basis of various toxicologic parameters. For the example of organophosphates, a methodological scheme was developed for conducting an accelerated experiment for predicting the chronic toxicity of low and average cumulative compounds. Results are presented indicating the inadvisability of using lower animals as test subjects with the aim of predicting toxicity for higher animals. It is pointed out that patterns of homology and isomerism are observed in the comparison of chronic intoxication threshold doses as well as in acute toxicity values of substances."} {"id": "PMID:1269512", "title": "Assessment of environmental carcinogen risks in terms of life shortening.", "content": "An approach is presented to the assessment of carcinogen risks in which the dominant effect of carcinogen exposure is life shortening and the impact falls both on those individuals who would have gotten cancer without the carcinogen exposure as well as the new cancer cases. This analysis is based on the interaction of age-specific tumor incidence rates and population survival in terms of age-specific mortality rates without the induced risk from carcinogen exposure. The analysis yields estimates for lifetime probability of developing cancer, average lifespan lost by the entire population, the average age of cancer occurrence, and the average lifespan loss of cancer cases. The approach utilizes the animal response data to assign, to the existing human cancer occurrence, and equivalent dose of the same carcinogen which is under consideration in terms of risk evaluation. The approach has the advantages of keying the estimates of carcinogen risks to those which already exist in the environment, advoiding large extrapolations from animal data, and encompassing the variability in susceptibility and carcinogen exposure in humans.", "contents": "Assessment of environmental carcinogen risks in terms of life shortening. An approach is presented to the assessment of carcinogen risks in which the dominant effect of carcinogen exposure is life shortening and the impact falls both on those individuals who would have gotten cancer without the carcinogen exposure as well as the new cancer cases. This analysis is based on the interaction of age-specific tumor incidence rates and population survival in terms of age-specific mortality rates without the induced risk from carcinogen exposure. The analysis yields estimates for lifetime probability of developing cancer, average lifespan lost by the entire population, the average age of cancer occurrence, and the average lifespan loss of cancer cases. The approach utilizes the animal response data to assign, to the existing human cancer occurrence, and equivalent dose of the same carcinogen which is under consideration in terms of risk evaluation. The approach has the advantages of keying the estimates of carcinogen risks to those which already exist in the environment, advoiding large extrapolations from animal data, and encompassing the variability in susceptibility and carcinogen exposure in humans."} {"id": "PMID:1269513", "title": "Predicting the risk of tumor occurrence under the effect of small doses of carcinogens.", "content": "Basic methodological approaches were formulated for determining the permissible levels of carcinogens in man's environment on the basis of current experimental oncological data dealing with the interaction of the organism and carcinogenic compounds. The tumor is proposed as a specific index of the harmfulness criterion of carcinogenic action. Under these conditions, both the frequency and the development time of tumors must be considered. Results are given of an experimental study of the carcinogenic activity of various doses of benz[a]pyrene (0.005, 0.02, 0.1, 0.5, and 2.5 mg) on rats by using a tenfold intratracheal administration. On the basis of mathematical models of the obtained dose-time-effect relationship, the risk of cancer occurrence due to small carcinogen doses is predicted. Small doses were not tested in the experiment. On the basis of the data obtained in the experiment, a maximally permissible concentration of benz a pyrene in the ambient air can be determined. A benz[a]pyrene dose of 0.02 mg is recommended as the basis of the calculation. The effect of this dose is shown at time periods longer than the limits of human life.", "contents": "Predicting the risk of tumor occurrence under the effect of small doses of carcinogens. Basic methodological approaches were formulated for determining the permissible levels of carcinogens in man's environment on the basis of current experimental oncological data dealing with the interaction of the organism and carcinogenic compounds. The tumor is proposed as a specific index of the harmfulness criterion of carcinogenic action. Under these conditions, both the frequency and the development time of tumors must be considered. Results are given of an experimental study of the carcinogenic activity of various doses of benz[a]pyrene (0.005, 0.02, 0.1, 0.5, and 2.5 mg) on rats by using a tenfold intratracheal administration. On the basis of mathematical models of the obtained dose-time-effect relationship, the risk of cancer occurrence due to small carcinogen doses is predicted. Small doses were not tested in the experiment. On the basis of the data obtained in the experiment, a maximally permissible concentration of benz a pyrene in the ambient air can be determined. A benz[a]pyrene dose of 0.02 mg is recommended as the basis of the calculation. The effect of this dose is shown at time periods longer than the limits of human life."} {"id": "PMID:1269514", "title": "[Studies on the value of fecal tryptic and chymotryptic activity in the diagnosis and therapy of cystic fibrosis (author's transl)].", "content": "Under certain conditions the determination of the tryptic activity, especially of the chymotryptic activity in the feces mostly of infants in the first 4-6 weeks of life is considered to be an important step in the diagnosis of cystic fibrosis. The tryptic anc chymotryptic activity in the feces of children with cystic fibrosis declines when the substitution of pancreatic enzymes is stopped. On resubstitution, the activity rises in relation to the dose and attains the activity related to age as found in healthy children. A comparison of the proteolytic activity with the fat content of the feces during the study period without the enzyme substitution and during the period when the enzyme dosage varied showed no significant correlation. It is not possible to postulate a poor excretion of fats merely from the high proteolytic activity of the feces because the fecal proteolytic activity and the fat excretion are not inversely proportional to one another. For this reason, one cannot conclude that the grade of the proteolytic activity in the feces of patients with cystic fibrosis is a yardstick for the total digestive process when they are under pancreatic enzyme substitution.", "contents": "[Studies on the value of fecal tryptic and chymotryptic activity in the diagnosis and therapy of cystic fibrosis (author's transl)]. Under certain conditions the determination of the tryptic activity, especially of the chymotryptic activity in the feces mostly of infants in the first 4-6 weeks of life is considered to be an important step in the diagnosis of cystic fibrosis. The tryptic anc chymotryptic activity in the feces of children with cystic fibrosis declines when the substitution of pancreatic enzymes is stopped. On resubstitution, the activity rises in relation to the dose and attains the activity related to age as found in healthy children. A comparison of the proteolytic activity with the fat content of the feces during the study period without the enzyme substitution and during the period when the enzyme dosage varied showed no significant correlation. It is not possible to postulate a poor excretion of fats merely from the high proteolytic activity of the feces because the fecal proteolytic activity and the fat excretion are not inversely proportional to one another. For this reason, one cannot conclude that the grade of the proteolytic activity in the feces of patients with cystic fibrosis is a yardstick for the total digestive process when they are under pancreatic enzyme substitution."} {"id": "PMID:1269515", "title": "Malignant disease of infancy and childhood with special reference to leukaemia: a survey of 6431 autopsy cases.", "content": "A study on the prevalence of cancer at autopsy in Chilean children with special reference to leukaemia, was made. In a series of 15300 consecutive autopsies of Chileans, 70% of deceased patients had an autopsy. Of these 15300 cases (male:female ratio 1:0.92) 6431 were children (0-15 years of age); 90% of deceased children patients had an autopsy. The autopsy population of children and adults is a homogeneous ethnic group, and exhibits a low socioeconomic level. Data on the 6431 post-mortem examinations (1945-1966) came from the atuopsy records of five hospitals (four of them are teaching hospitals) in the city of Santiago. Each one of the leukaemia and solid tumour cases were diagnosed microscopically. In the children population, 54.92% were males and 45.08% were females. Of the 6431 autopsies, 142 exhibited cancer (2.21%), 2.43% being male cases and 1.93% being female cases. The autopsy cases showed a marked excess of boys (73.92%) and girls (69.77%) under 1 year of age. The prevalence of major morphological groups of cancer was as follows: leukaemias 50.70%, intracranial and other neural neoplasms 25.35%, malignant lymphomas, including Hodgkin's disease, 14.07%, and mixed malignant tumours (Wilms' tumour) 4.93%. 4.93%. Acute leukaemias (42.96%), medulloblastoma (7.65%), Hodgkin's disease (6.34%), Wilms' tumour (4.93%), and lymphosarcoma (4.93%) were the most prevalent types of cancer. Leukaemia cases had a corrected male:female ratio of 1:0.61. The prevalence of leukaemia in the atuopsy population was 1.12%.", "contents": "Malignant disease of infancy and childhood with special reference to leukaemia: a survey of 6431 autopsy cases. A study on the prevalence of cancer at autopsy in Chilean children with special reference to leukaemia, was made. In a series of 15300 consecutive autopsies of Chileans, 70% of deceased patients had an autopsy. Of these 15300 cases (male:female ratio 1:0.92) 6431 were children (0-15 years of age); 90% of deceased children patients had an autopsy. The autopsy population of children and adults is a homogeneous ethnic group, and exhibits a low socioeconomic level. Data on the 6431 post-mortem examinations (1945-1966) came from the atuopsy records of five hospitals (four of them are teaching hospitals) in the city of Santiago. Each one of the leukaemia and solid tumour cases were diagnosed microscopically. In the children population, 54.92% were males and 45.08% were females. Of the 6431 autopsies, 142 exhibited cancer (2.21%), 2.43% being male cases and 1.93% being female cases. The autopsy cases showed a marked excess of boys (73.92%) and girls (69.77%) under 1 year of age. The prevalence of major morphological groups of cancer was as follows: leukaemias 50.70%, intracranial and other neural neoplasms 25.35%, malignant lymphomas, including Hodgkin's disease, 14.07%, and mixed malignant tumours (Wilms' tumour) 4.93%. 4.93%. Acute leukaemias (42.96%), medulloblastoma (7.65%), Hodgkin's disease (6.34%), Wilms' tumour (4.93%), and lymphosarcoma (4.93%) were the most prevalent types of cancer. Leukaemia cases had a corrected male:female ratio of 1:0.61. The prevalence of leukaemia in the atuopsy population was 1.12%."} {"id": "PMID:1269516", "title": "Hemoglobin chain synthesis in two children with trisomy 13. Evidence for temporary imbalance during switch from gamma to beta chain synthesis.", "content": "Hemoglobin chain synthesis was studied in 2 infants with trisomy 13, one in the newborn period, the other at 5 months of age. The relative rate of beta globin synthesis was much below normal in the newborn, resulting in an overall imbalance of nonalpha/alpha globin synthesis. In the 5-month-old child, globin synthesis was balanced, although gamma globin synthesis accounted for a larger than normal percentage of nonalpha globin synthesis. Thus, the presence of a third 13 chromosome causes sever disturbances in the gamma to beta switch mechanism primarily affecting the onset of beta globin synthesis. The appearance of two previously unobserved bands in isoelectric focusing gels of the newborn's Hb is suggestive of the presence of embryonic hemoglobins.", "contents": "Hemoglobin chain synthesis in two children with trisomy 13. Evidence for temporary imbalance during switch from gamma to beta chain synthesis. Hemoglobin chain synthesis was studied in 2 infants with trisomy 13, one in the newborn period, the other at 5 months of age. The relative rate of beta globin synthesis was much below normal in the newborn, resulting in an overall imbalance of nonalpha/alpha globin synthesis. In the 5-month-old child, globin synthesis was balanced, although gamma globin synthesis accounted for a larger than normal percentage of nonalpha globin synthesis. Thus, the presence of a third 13 chromosome causes sever disturbances in the gamma to beta switch mechanism primarily affecting the onset of beta globin synthesis. The appearance of two previously unobserved bands in isoelectric focusing gels of the newborn's Hb is suggestive of the presence of embryonic hemoglobins."} {"id": "PMID:1269517", "title": "Mean 24-hour growth hormone and testosterone concentrations in relation to pubertal growth spurt in boys with normal or delayed puberty.", "content": "The mean growth hormone concentration during 24-hour period in 7 boys of short familial stature and a growth rate of 3.2-5.4 cm/year was between 1.0 and 4.6 ng/ml serum. In 7 boys with pubertal growth spurt and familial tallness (growth rate 7.2-11.0 cm/year) it varied from 0.97 to 4.4 ng/ml and in 6 boys with constitutional delay of puberty (a growth rate of 4.2-5.2 cm/year prior to puberty) from 1.3 to 4.3 ng/ml. No correlation was found between the 24-hour mean growth hormone concentration and the mean 24-hour testosterone concentration in serum or the growth rate, but a correlation was found between testosterone and the growth rate. It is concluded that the growth spurt in puberty is not due to a change in growth hormone concentration but rather to the increase of androgen production in puberty.", "contents": "Mean 24-hour growth hormone and testosterone concentrations in relation to pubertal growth spurt in boys with normal or delayed puberty. The mean growth hormone concentration during 24-hour period in 7 boys of short familial stature and a growth rate of 3.2-5.4 cm/year was between 1.0 and 4.6 ng/ml serum. In 7 boys with pubertal growth spurt and familial tallness (growth rate 7.2-11.0 cm/year) it varied from 0.97 to 4.4 ng/ml and in 6 boys with constitutional delay of puberty (a growth rate of 4.2-5.2 cm/year prior to puberty) from 1.3 to 4.3 ng/ml. No correlation was found between the 24-hour mean growth hormone concentration and the mean 24-hour testosterone concentration in serum or the growth rate, but a correlation was found between testosterone and the growth rate. It is concluded that the growth spurt in puberty is not due to a change in growth hormone concentration but rather to the increase of androgen production in puberty."} {"id": "PMID:1269550", "title": "The problem of toxicity in the bioassay for erythropoietin using mouse fetal liver cells.", "content": "The use of neonatal instead of fetal calf serum, as a constituent of the culture medium, confronted the authors with the problem of toxicity in the fetal liver cell erythropoietin assay. Tested human sera were toxic at rather low concentrations. Heating the human sera for 30 min at 56 degrees C abolished the toxicity. Heating the Step I or Step III sheep plasma erythropoietin had very little influence. Fetal calf serum proved to be more suitable than neonatal calf serum for two reasons: The toxicity of human sera was less pronounced when fetal calf serum was used in the medium, and it gave a wider separation of unstimulated and maximally stimulated cultures.", "contents": "The problem of toxicity in the bioassay for erythropoietin using mouse fetal liver cells. The use of neonatal instead of fetal calf serum, as a constituent of the culture medium, confronted the authors with the problem of toxicity in the fetal liver cell erythropoietin assay. Tested human sera were toxic at rather low concentrations. Heating the human sera for 30 min at 56 degrees C abolished the toxicity. Heating the Step I or Step III sheep plasma erythropoietin had very little influence. Fetal calf serum proved to be more suitable than neonatal calf serum for two reasons: The toxicity of human sera was less pronounced when fetal calf serum was used in the medium, and it gave a wider separation of unstimulated and maximally stimulated cultures."} {"id": "PMID:1269551", "title": "Effect of Rauscher leukemia development on DNA synthesis by hematopoietic CFU-S.", "content": "The effect of Rauscher viral leukemia on the number of colony forming cells (CFU-S) in the spleen has been measured as a function of time after virus administration. These were increased substantially after the first week, reaching a maximum at 2 weeks, after which they decreased in number. Determination of the proportion of these CFU-S which were in DNA synthesis was carried out using the in vitro 3HTdR suicide technique. Within 4 hours of injection of the virus the number of spleen CFU-S which could be inactivated by in vitro 3HTdR exposure increased to 20.9% from a normal mean value of 10.2%. For the next 2 weeks the proportion of CFU-S responding to tritiated thymidine exposure remained at the same value of approximately 20%; the change in number of surviving CFU-S roughly paralleled the change in total colony forming cells. In the third week after virus injection, the proportion of CFU-S which was inactivated by 3HTdR decreased to the point where it could no longer be detected, even though the total number of CFU-S was elevated several fold over the normal. These findings indicate that infection with moderate dose levels of Rauscher virus does result in a measurable early increase in the proportion of cells in DNA synthesis. However, the failure to detect further substantial increases as the disease develops suggests that the virus of itself is not an initiator of all the steps of DNA synthesis. Rather, it would appear that it is to some degree dependent upon other aspects of normal DNA synthesis which remain under control of the cell.", "contents": "Effect of Rauscher leukemia development on DNA synthesis by hematopoietic CFU-S. The effect of Rauscher viral leukemia on the number of colony forming cells (CFU-S) in the spleen has been measured as a function of time after virus administration. These were increased substantially after the first week, reaching a maximum at 2 weeks, after which they decreased in number. Determination of the proportion of these CFU-S which were in DNA synthesis was carried out using the in vitro 3HTdR suicide technique. Within 4 hours of injection of the virus the number of spleen CFU-S which could be inactivated by in vitro 3HTdR exposure increased to 20.9% from a normal mean value of 10.2%. For the next 2 weeks the proportion of CFU-S responding to tritiated thymidine exposure remained at the same value of approximately 20%; the change in number of surviving CFU-S roughly paralleled the change in total colony forming cells. In the third week after virus injection, the proportion of CFU-S which was inactivated by 3HTdR decreased to the point where it could no longer be detected, even though the total number of CFU-S was elevated several fold over the normal. These findings indicate that infection with moderate dose levels of Rauscher virus does result in a measurable early increase in the proportion of cells in DNA synthesis. However, the failure to detect further substantial increases as the disease develops suggests that the virus of itself is not an initiator of all the steps of DNA synthesis. Rather, it would appear that it is to some degree dependent upon other aspects of normal DNA synthesis which remain under control of the cell."} {"id": "PMID:1269552", "title": "Effect of serum from leukapheresed mice on myelocytes, promyelocytes and colony-forming cells.", "content": "Leukapheresis of neutrophil granulocytes in mice increased the myelopoietic activity of their serum. Leukapheresed mouse serum (LMS) caused a threefold increase in the in vitro stathmokinetic index of myeloid precursors. Five to ten minutes of incubation were sufficient to change the colony-forming capacity of mouse bone marrow cells as expressed by the increase in the ratio of granuloid to erythroid cells in spleen colonies. The in vitro stathmokinetic index assay also showed that there are diurnal variations in levels of granulopoietic activity in normal mouse sera. However, at any time of the day, LMS had higher granulopoietic activity.", "contents": "Effect of serum from leukapheresed mice on myelocytes, promyelocytes and colony-forming cells. Leukapheresis of neutrophil granulocytes in mice increased the myelopoietic activity of their serum. Leukapheresed mouse serum (LMS) caused a threefold increase in the in vitro stathmokinetic index of myeloid precursors. Five to ten minutes of incubation were sufficient to change the colony-forming capacity of mouse bone marrow cells as expressed by the increase in the ratio of granuloid to erythroid cells in spleen colonies. The in vitro stathmokinetic index assay also showed that there are diurnal variations in levels of granulopoietic activity in normal mouse sera. However, at any time of the day, LMS had higher granulopoietic activity."} {"id": "PMID:1269553", "title": "Correlation between splenic phagocytic activity and increase in splenic granulocyte/macrophage progenitors.", "content": "The possible connection between changes in splenic phagocytic activity and increase of splenic macrophage/granulocyte progenitors (colony forming cells - CFC) in mice was studied. Intravenous administration of increasing amounts of colloidal carbon, or sheep red blood cells (SRBC), 3 hours prior to injection of 10(7) 51Cr labeled SRBC caused a decrease in phagocytic activity in liver and an increase in spleen. Under the same experimental conditions, injection 10(7) unlabeled SRBC induced an increase of splenic CFC. Increase in splenic phagocytic activity and in numbers of splenic CFC showed a linear relationship. Both activities depended on the amounts of colloidal carbon or SRBC injected prior to injection of 10(7) SRBC. These findings suggest that mature macrophages may participate in controlling the increase in number of splenic CFC after injection of particulate substances such as SRBC or colloidal carbon. It was also found that increase of splenic CFC, under the experimental conditions described, was not affected by neonatal thymectomy.", "contents": "Correlation between splenic phagocytic activity and increase in splenic granulocyte/macrophage progenitors. The possible connection between changes in splenic phagocytic activity and increase of splenic macrophage/granulocyte progenitors (colony forming cells - CFC) in mice was studied. Intravenous administration of increasing amounts of colloidal carbon, or sheep red blood cells (SRBC), 3 hours prior to injection of 10(7) 51Cr labeled SRBC caused a decrease in phagocytic activity in liver and an increase in spleen. Under the same experimental conditions, injection 10(7) unlabeled SRBC induced an increase of splenic CFC. Increase in splenic phagocytic activity and in numbers of splenic CFC showed a linear relationship. Both activities depended on the amounts of colloidal carbon or SRBC injected prior to injection of 10(7) SRBC. These findings suggest that mature macrophages may participate in controlling the increase in number of splenic CFC after injection of particulate substances such as SRBC or colloidal carbon. It was also found that increase of splenic CFC, under the experimental conditions described, was not affected by neonatal thymectomy."} {"id": "PMID:1269554", "title": "Thymic influence of proliferation and interaction of fractionated spleen cells of mice.", "content": "Cells from the spleens of mice were separated into seven subpopulations by centrifugation on a discontinuous density gradient of dextran. The lightest fraction (containing stem cells), the three heaviest fractions (containing small lymphocytes), or a mixture of these, were injected into thymectomized or sham-thymectomized irradiated mice together with sheep red blood cells as antigen. After 8 days, the spleens of treated mice were tested for their content of cells lysing sheep red blood cells in agar (PFC) or cells mounting graft-versus-host reaction in newborn mice (GVHR). Heavy fractions were depleted of progenitors of PFC, but contained progenitors of cells mounting GVHR. The light fraction was depleted of both. If light cells were given together with heavy ones, the potential to generate PFC was restored, but only if the recipients were without their thymus; by contrast, the potential to generate GVH-reactive cells was strongly suppressed in the absence of a thymus. It is concluded that, in this model, stem cells probably interact with immunocompetent cells, and that the interaction depends on the thymus.", "contents": "Thymic influence of proliferation and interaction of fractionated spleen cells of mice. Cells from the spleens of mice were separated into seven subpopulations by centrifugation on a discontinuous density gradient of dextran. The lightest fraction (containing stem cells), the three heaviest fractions (containing small lymphocytes), or a mixture of these, were injected into thymectomized or sham-thymectomized irradiated mice together with sheep red blood cells as antigen. After 8 days, the spleens of treated mice were tested for their content of cells lysing sheep red blood cells in agar (PFC) or cells mounting graft-versus-host reaction in newborn mice (GVHR). Heavy fractions were depleted of progenitors of PFC, but contained progenitors of cells mounting GVHR. The light fraction was depleted of both. If light cells were given together with heavy ones, the potential to generate PFC was restored, but only if the recipients were without their thymus; by contrast, the potential to generate GVH-reactive cells was strongly suppressed in the absence of a thymus. It is concluded that, in this model, stem cells probably interact with immunocompetent cells, and that the interaction depends on the thymus."} {"id": "PMID:1269555", "title": "Evoked cerebral responses to noxious thermal stimuli in humans.", "content": "Brief pulses of Laser emitted radiant heat were used to induce cutaneous painful sensations in human volunteers. Accurate timing of the stimuli permitted recording of scalp averaged evoked potentials. A late negative-positive component of the EP which correlated in amplitude with the subjective sensation was observed in four subjects. The latency of this component (130-160 msec) correlated with stimulus intensity.", "contents": "Evoked cerebral responses to noxious thermal stimuli in humans. Brief pulses of Laser emitted radiant heat were used to induce cutaneous painful sensations in human volunteers. Accurate timing of the stimuli permitted recording of scalp averaged evoked potentials. A late negative-positive component of the EP which correlated in amplitude with the subjective sensation was observed in four subjects. The latency of this component (130-160 msec) correlated with stimulus intensity."} {"id": "PMID:1269556", "title": "Behavioural compensation of cats after early rotation of one eye.", "content": "Two cats, each with one eye surgically rotated by about 90, were trained (by two different behavioural methods) to discriminate horizontal from vertical stripes using the normal eye alone. When they had mastered the discrimination, the normal eye was occluded and the rotated eye was tested for transfer with neither stimulus reinforced. Both cats responded immediately and consistently to the same stimulus that they had learned to choose with the normal eye. These animals seem to have adapted to eye-rotation not only in terms of spatial localization but also in terms of the recognition of the orientation of contours. These behavioural compensations cannot be accounted for by simple changes in the organization of the visual cortex.", "contents": "Behavioural compensation of cats after early rotation of one eye. Two cats, each with one eye surgically rotated by about 90, were trained (by two different behavioural methods) to discriminate horizontal from vertical stripes using the normal eye alone. When they had mastered the discrimination, the normal eye was occluded and the rotated eye was tested for transfer with neither stimulus reinforced. Both cats responded immediately and consistently to the same stimulus that they had learned to choose with the normal eye. These animals seem to have adapted to eye-rotation not only in terms of spatial localization but also in terms of the recognition of the orientation of contours. These behavioural compensations cannot be accounted for by simple changes in the organization of the visual cortex."} {"id": "PMID:1269557", "title": "Effect of oxotremorine on the response of antidromically activated Renshaw cells in decerebrate cats.", "content": "In intercollicular decerebrate cats, some of which were made spinal in addition, the effect of oxotremorine (intravenous injection, 10-30 mug/kg) was tested on antidromically activated Renshaw cells. Methylatropine premedication prevented the otherwise often fatal drop in blood pressure; ipsilateral dorsal roots L6-S1 and contralateral hindlimb nerves were cut to exclude segmental receptor interference. During supramaximal stimulation of ventral root L7 or the gastrocnemius nerves, an increase of activity ranging from 10-110% was observed. The drug occasionally evoked spontaneous discharges in Renshaw cells, or enhanced activity already present. Alpha motoneuron activity decreased in most cases. The interaction of oxotremorine with atropine and eserine was also investigated on Renshaw cells. Our results suggest that one of the effects of oxotremorine may be a disbalance between motor output and recurrent inhibition.", "contents": "Effect of oxotremorine on the response of antidromically activated Renshaw cells in decerebrate cats. In intercollicular decerebrate cats, some of which were made spinal in addition, the effect of oxotremorine (intravenous injection, 10-30 mug/kg) was tested on antidromically activated Renshaw cells. Methylatropine premedication prevented the otherwise often fatal drop in blood pressure; ipsilateral dorsal roots L6-S1 and contralateral hindlimb nerves were cut to exclude segmental receptor interference. During supramaximal stimulation of ventral root L7 or the gastrocnemius nerves, an increase of activity ranging from 10-110% was observed. The drug occasionally evoked spontaneous discharges in Renshaw cells, or enhanced activity already present. Alpha motoneuron activity decreased in most cases. The interaction of oxotremorine with atropine and eserine was also investigated on Renshaw cells. Our results suggest that one of the effects of oxotremorine may be a disbalance between motor output and recurrent inhibition."} {"id": "PMID:1269558", "title": "Characteristics of single mechanoreceptive fibres innervating hairy skin of the human hand.", "content": "Unit activity was recorded percutaneously by microelectrodes from 69 nerve fibres innervating the hairy skin of the back of the hand in 6 awake human subjects. Twelve fibres had no receptive field on the skin, twenty-one fibres could be classified as rapidly adapting (RA) and thiry-six fibres as slowly adapting (SA) mechanoreceptive fibres. Four SA fibres has a spontaneous discharge in absence of stimulation. Mechanical thresholds of tra fibres ranged from 0.3 to 1.7 g and those of SA fibres from less than 0.1 to 1.7 g. Conduction velocities of the fibres were 22-41 m/s (RA fibres) and 10-73 m/s (SA fibres). Intensity functions of SA fibres could be described by power functions with exponents varying between 0.31-1.23. Most RA and SA fibres were entrained by vibratory stimuli. The results indicate that the receptors in the human hairy skin do not differ considerably in their characteristics from the receptors in the human glabrous skin or from animal receptors in the hairy skin.", "contents": "Characteristics of single mechanoreceptive fibres innervating hairy skin of the human hand. Unit activity was recorded percutaneously by microelectrodes from 69 nerve fibres innervating the hairy skin of the back of the hand in 6 awake human subjects. Twelve fibres had no receptive field on the skin, twenty-one fibres could be classified as rapidly adapting (RA) and thiry-six fibres as slowly adapting (SA) mechanoreceptive fibres. Four SA fibres has a spontaneous discharge in absence of stimulation. Mechanical thresholds of tra fibres ranged from 0.3 to 1.7 g and those of SA fibres from less than 0.1 to 1.7 g. Conduction velocities of the fibres were 22-41 m/s (RA fibres) and 10-73 m/s (SA fibres). Intensity functions of SA fibres could be described by power functions with exponents varying between 0.31-1.23. Most RA and SA fibres were entrained by vibratory stimuli. The results indicate that the receptors in the human hairy skin do not differ considerably in their characteristics from the receptors in the human glabrous skin or from animal receptors in the hairy skin."} {"id": "PMID:1269559", "title": "Properties of LGN cells in kittens reared with convergent squint: a neurophysiological demonstration of amblyopia.", "content": "The spatial resolution of LGN cells has been studied in 4-5 month old kittens raised with convergent squint surgically produced in one eye at the age of 3-4 weeks. The 'sustained' cells which received inputs from the central retina of the squint eye showed significantly poorer spatial resolution (determined by the highest spatial frequency of a sinusoidal grating to which a cell responded with modulated firing) than those which received inputs from the central retina of the normal eye. The spatial resolution of cells which received inputs from the peripheral retina of the squint eye was not different from that of cells receiving inputs from the peripheral retina of the normal eye. The visual latency of 'sustained' cells which received an input from the area centralis of the squint eye was considerably lenghtned and the response showed a sluggish onset. Thus the most important clinical symptom of amblyopia, namely the reduction of foveal visual acuity, has been demonstrated in kittens raised with unilateral vonvergent squint. The results suggest that the lesion responsible for amblyopia due to squint might be a functional degeneration of the high spatial frequency tuning cells in the pathway prior to the visual cortex, i.e. in the retina or LGN.", "contents": "Properties of LGN cells in kittens reared with convergent squint: a neurophysiological demonstration of amblyopia. The spatial resolution of LGN cells has been studied in 4-5 month old kittens raised with convergent squint surgically produced in one eye at the age of 3-4 weeks. The 'sustained' cells which received inputs from the central retina of the squint eye showed significantly poorer spatial resolution (determined by the highest spatial frequency of a sinusoidal grating to which a cell responded with modulated firing) than those which received inputs from the central retina of the normal eye. The spatial resolution of cells which received inputs from the peripheral retina of the squint eye was not different from that of cells receiving inputs from the peripheral retina of the normal eye. The visual latency of 'sustained' cells which received an input from the area centralis of the squint eye was considerably lenghtned and the response showed a sluggish onset. Thus the most important clinical symptom of amblyopia, namely the reduction of foveal visual acuity, has been demonstrated in kittens raised with unilateral vonvergent squint. The results suggest that the lesion responsible for amblyopia due to squint might be a functional degeneration of the high spatial frequency tuning cells in the pathway prior to the visual cortex, i.e. in the retina or LGN."} {"id": "PMID:1269560", "title": "14-3-2 protein in rat primary and transplanted gliomas and neurinomas and in clonal cell lines.", "content": "Experimental neurogenic tumors were induced transplacentally in rats by single injections of ethylnitrosourea (ENU). The resulting primary tumors as well as isogenic transplantation tumor lines and clonal cell lines derived therefrom were examined for their content of the brain specific protein 14-3-2 by a quantitative microcomplement fixation assay. The content of S-100 protein in the samples studied is given as well. Some of the tumors of glial or Schwann cell origin did contain 14-3-2 protein ranging from 0.6 to 1.5 mug 14-3-2 per mg total soluble protein. Our experiments also showed that the ability of a tumor to produce this specific protein is transplantable over a series of subcutaneous isogenic transplantations while in the transplantation tumors the content of this protein seemed to be reduced. We were not able so far to find a correlation between the morphology of a tumor and its capability to produce a specific protein. The clonal cell line RN2 of Schwann cell origin which has been previously described in detail contained both the brain specific proteins 14-3-2 and S-100 in comparable amounts ranging from 0.3 to 0.6 and from 0.4 to 1.0 mug specific protein per total soluble protein respectively.", "contents": "14-3-2 protein in rat primary and transplanted gliomas and neurinomas and in clonal cell lines. Experimental neurogenic tumors were induced transplacentally in rats by single injections of ethylnitrosourea (ENU). The resulting primary tumors as well as isogenic transplantation tumor lines and clonal cell lines derived therefrom were examined for their content of the brain specific protein 14-3-2 by a quantitative microcomplement fixation assay. The content of S-100 protein in the samples studied is given as well. Some of the tumors of glial or Schwann cell origin did contain 14-3-2 protein ranging from 0.6 to 1.5 mug 14-3-2 per mg total soluble protein. Our experiments also showed that the ability of a tumor to produce this specific protein is transplantable over a series of subcutaneous isogenic transplantations while in the transplantation tumors the content of this protein seemed to be reduced. We were not able so far to find a correlation between the morphology of a tumor and its capability to produce a specific protein. The clonal cell line RN2 of Schwann cell origin which has been previously described in detail contained both the brain specific proteins 14-3-2 and S-100 in comparable amounts ranging from 0.3 to 0.6 and from 0.4 to 1.0 mug specific protein per total soluble protein respectively."} {"id": "PMID:1269589", "title": "Stability of distance between structured groups in a social organism: empirical research.", "content": "The working hypothesis at the basis of the research is that in the development process of a social body the distance between structural groups of persons remain constant. The structural groups considered are men, women and a selected group of women (Soroptimists). The inquiry was carried out in 15 European countries in 1972. The total number of interviews was 4200. The six variables considered in the inquiry are the attitudes in respect of work, family, education, free time, sex and politics. The discriminatory analysis techniques are: entropy and factor analysis. Results seem to confirm the hypothesis of stability between groups and of countries between one another.", "contents": "Stability of distance between structured groups in a social organism: empirical research. The working hypothesis at the basis of the research is that in the development process of a social body the distance between structural groups of persons remain constant. The structural groups considered are men, women and a selected group of women (Soroptimists). The inquiry was carried out in 15 European countries in 1972. The total number of interviews was 4200. The six variables considered in the inquiry are the attitudes in respect of work, family, education, free time, sex and politics. The discriminatory analysis techniques are: entropy and factor analysis. Results seem to confirm the hypothesis of stability between groups and of countries between one another."} {"id": "PMID:1269594", "title": "Retinol and retinyl esters in pigment epithelium of rats with inherited retinal degeneration.", "content": "A comparative study of the retinol and retinyl ester concentrations was performed in the retinal pigment epithelium of the normal and affected rats. Our findings indicate that in dystrophic rat retinol content increases, whereas the amount of retinyl esters is always lower than normal. An hypothesis can be made on the deficiency of enzymic activities which regulate retinol retinol and retinyl esters levels in the pigment epithelium.", "contents": "Retinol and retinyl esters in pigment epithelium of rats with inherited retinal degeneration. A comparative study of the retinol and retinyl ester concentrations was performed in the retinal pigment epithelium of the normal and affected rats. Our findings indicate that in dystrophic rat retinol content increases, whereas the amount of retinyl esters is always lower than normal. An hypothesis can be made on the deficiency of enzymic activities which regulate retinol retinol and retinyl esters levels in the pigment epithelium."} {"id": "PMID:1269597", "title": "Dense particles in subcutaneous collagen fibrils.", "content": "Electron microscopy of unstained, fresh air-dried spreads of the subcutaneous connective tissue disclosed dense particles (6-20 nm in diameter) at the dark bands of collagen fibrils with 67 nm periodicity. The particles appear to consist of chlorides from the X-ray microanalysis of collagen fibres.", "contents": "Dense particles in subcutaneous collagen fibrils. Electron microscopy of unstained, fresh air-dried spreads of the subcutaneous connective tissue disclosed dense particles (6-20 nm in diameter) at the dark bands of collagen fibrils with 67 nm periodicity. The particles appear to consist of chlorides from the X-ray microanalysis of collagen fibres."} {"id": "PMID:1269600", "title": "Effects of alanine, glycine and glutamic acid on nitrogenous excretion by Amphiuma means liver in organ culture.", "content": "High concentrations (10 mM) of alanine, glycine, and glutamic acid in the culture medium had no effect on urea production in Amphiuma means liver in organ culture. Ammonia production was increased in media containing added alanine and glycine, but reduced in medium with added glutamic acid.", "contents": "Effects of alanine, glycine and glutamic acid on nitrogenous excretion by Amphiuma means liver in organ culture. High concentrations (10 mM) of alanine, glycine, and glutamic acid in the culture medium had no effect on urea production in Amphiuma means liver in organ culture. Ammonia production was increased in media containing added alanine and glycine, but reduced in medium with added glutamic acid."} {"id": "PMID:1269601", "title": "Field testing of cis-11-tetradecenal as attractant or synergist in Tortricinae.", "content": "Field studies have shown that cis-11-tetradecenal is an effective attractant for male Choristoneura conflictana, a pest of aspen. These studies also indicate that cis-11-tetradecenal is probably a secondary component in the sex pheromone systems of Choristoneura rosaceana and Choristoneura fumiferana.", "contents": "Field testing of cis-11-tetradecenal as attractant or synergist in Tortricinae. Field studies have shown that cis-11-tetradecenal is an effective attractant for male Choristoneura conflictana, a pest of aspen. These studies also indicate that cis-11-tetradecenal is probably a secondary component in the sex pheromone systems of Choristoneura rosaceana and Choristoneura fumiferana."} {"id": "PMID:1269604", "title": "Long-chain (Z)-9-alkenes are \"psychedelics\" to houseflies with regard to visually stimulated sex attraction and aggregation.", "content": "Three different tests on houseflies (Musca domestica L.) revealed that both pheromone-free pseudoflies and male partner flies exhibit in the presence of mixtures of long-chain (Z)-9-alkenes or pure (Z)-9-tricosene enhanced releasing effects for two optical cues, which stimulate male houseflies to mating strikes and houseflies of both sexes to aggregation.", "contents": "Long-chain (Z)-9-alkenes are \"psychedelics\" to houseflies with regard to visually stimulated sex attraction and aggregation. Three different tests on houseflies (Musca domestica L.) revealed that both pheromone-free pseudoflies and male partner flies exhibit in the presence of mixtures of long-chain (Z)-9-alkenes or pure (Z)-9-tricosene enhanced releasing effects for two optical cues, which stimulate male houseflies to mating strikes and houseflies of both sexes to aggregation."} {"id": "PMID:1269605", "title": "Sodium pumps and galactose transfer in the short-circuited small intestine.", "content": "In a short-circuited preparation of rat jejunum, there are two sodium pumps, one electrogenic and the other neutral. When energy sources are limited, the total sodium transfer is limited. In the presence of a non-metabolized actively transferred hexose, the electrogenic pump is preferentially used. The neutral sodium pump is only able to function when additional energy is available.", "contents": "Sodium pumps and galactose transfer in the short-circuited small intestine. In a short-circuited preparation of rat jejunum, there are two sodium pumps, one electrogenic and the other neutral. When energy sources are limited, the total sodium transfer is limited. In the presence of a non-metabolized actively transferred hexose, the electrogenic pump is preferentially used. The neutral sodium pump is only able to function when additional energy is available."} {"id": "PMID:1269608", "title": "Contraction of myoepithelial cells in secreting submandibular glands of dogs.", "content": "In slowly secreting submandibular glands of dogs, a sympathetic effect on myoepithelial cells was demonstrated as an acceleration of the flow, followed by retardation, on short-lasting sympathetic stimulation, particularly after beta-adrenoceptor-blocking drugs.", "contents": "Contraction of myoepithelial cells in secreting submandibular glands of dogs. In slowly secreting submandibular glands of dogs, a sympathetic effect on myoepithelial cells was demonstrated as an acceleration of the flow, followed by retardation, on short-lasting sympathetic stimulation, particularly after beta-adrenoceptor-blocking drugs."} {"id": "PMID:1269609", "title": "Physiological studies on the effects of nutritional imbalance on the central nervous system. II. Effects of thiamine deficiency on oxidative enzymes in the brain of chicken, Gallus domesticus.", "content": "The activitiy levels of succinate dehydrogenase, glutamate dehydrogenase and pyruvate dehydrogenase in the fore, mid and hind brain regions of the thiamine deficient chicken, Gallus domesticus were determined. The activity levels of succinate dehydrogenase and glutamate dehydrogenase in all the 3 regions of brain showed augmentation on inducing thiamine deficiency. In contrast the activity levels of pyruvate dehydrogenase decreased in the brain of thiamine deficient animals. It is suggested that these changes in the oxidative enzymes indicate disturbance caused in the operation of the tricarboxylic acid cycle in thiamine deficiency.", "contents": "Physiological studies on the effects of nutritional imbalance on the central nervous system. II. Effects of thiamine deficiency on oxidative enzymes in the brain of chicken, Gallus domesticus. The activitiy levels of succinate dehydrogenase, glutamate dehydrogenase and pyruvate dehydrogenase in the fore, mid and hind brain regions of the thiamine deficient chicken, Gallus domesticus were determined. The activity levels of succinate dehydrogenase and glutamate dehydrogenase in all the 3 regions of brain showed augmentation on inducing thiamine deficiency. In contrast the activity levels of pyruvate dehydrogenase decreased in the brain of thiamine deficient animals. It is suggested that these changes in the oxidative enzymes indicate disturbance caused in the operation of the tricarboxylic acid cycle in thiamine deficiency."} {"id": "PMID:1269610", "title": "Rhythmic cerebellar and cortical electric activity in tetanus intoxicated rabbits.", "content": "Intravenously injected tetanus toxin induced general tetanus within 12 to 37 h. The EEG of precentral, parietal, and occipital areas of the cerebellum revealed a highly rhythmic activity. In local tetanus of the limbs or in brainstem tetanus this rhythm could not be registered.", "contents": "Rhythmic cerebellar and cortical electric activity in tetanus intoxicated rabbits. Intravenously injected tetanus toxin induced general tetanus within 12 to 37 h. The EEG of precentral, parietal, and occipital areas of the cerebellum revealed a highly rhythmic activity. In local tetanus of the limbs or in brainstem tetanus this rhythm could not be registered."} {"id": "PMID:1269611", "title": "Potentiation of ethanol narcosis by dopamine- and l-DOPA-based isoquinolines.", "content": "The isoquinolines, salsolinol and 3-carboxysalsolinol, prolong ethanol-induced narcosis in mice. Pretreatment with carbidopa increases the effect of 3-carboxysalsolinol but not of salsolinol. These results suggest that ethanol sleeping-time potentiation by l-LOPA may involve a partial conversion to the isoquinoline in vivo. A central depressant action of salsolinol or the 3-carboxy analogue is suggested.", "contents": "Potentiation of ethanol narcosis by dopamine- and l-DOPA-based isoquinolines. The isoquinolines, salsolinol and 3-carboxysalsolinol, prolong ethanol-induced narcosis in mice. Pretreatment with carbidopa increases the effect of 3-carboxysalsolinol but not of salsolinol. These results suggest that ethanol sleeping-time potentiation by l-LOPA may involve a partial conversion to the isoquinoline in vivo. A central depressant action of salsolinol or the 3-carboxy analogue is suggested."} {"id": "PMID:1269612", "title": "Antitumor activity of the Isodon diterpenoids: structural requirements for the activity.", "content": "A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids of Isodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds 9 and 3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature.", "contents": "Antitumor activity of the Isodon diterpenoids: structural requirements for the activity. A significant antitumor activity of oridonin (1) and lasiokaurin (2), the kaurene-type diterpenoids of Isodon species, was shown by their i.p. injection to the test mice inoculated by Ehrlich ascites carcinoma. Enmein (8), compounds 9 and 3 were also active under larger dose. Subsequently, the relationship between their chemical structure and antitumor activity was investigated, and the activity of oridonin (1) and lasiokaurin (2) was rationalized in terms of their structural feature."} {"id": "PMID:1269615", "title": "Lithium effects upon components of activity in rats.", "content": "When lithium chloride was administered to rats several changes occurred in a number of components of activity, some of which were sex-related. There was a reduction in both ambulatory and rearing activity and in behaviour associated particularly with the mouth and nose. The findings are related to a suggestion that lithium effects on behaviour may be more subtle than hitherto thought.", "contents": "Lithium effects upon components of activity in rats. When lithium chloride was administered to rats several changes occurred in a number of components of activity, some of which were sex-related. There was a reduction in both ambulatory and rearing activity and in behaviour associated particularly with the mouth and nose. The findings are related to a suggestion that lithium effects on behaviour may be more subtle than hitherto thought."} {"id": "PMID:1269616", "title": "The action of substance P on mesencephalic reticular and substantia nigral neurones of the rat.", "content": "Extracellular recordings were made from neurones in the mesencephalic reticular formation and substantianigra of the rat which was anaesthetized with urethane 1.5-2 g/kg i.p. Out of 44 cells tested 42 were excited by Substance P applied iontophoretically and in some cases this excitation was rapid. Evidence is presented for Substance P as a putative excitatory transmitter onto reticular and nigral neurones possibly released from primary sensory afferents.", "contents": "The action of substance P on mesencephalic reticular and substantia nigral neurones of the rat. Extracellular recordings were made from neurones in the mesencephalic reticular formation and substantianigra of the rat which was anaesthetized with urethane 1.5-2 g/kg i.p. Out of 44 cells tested 42 were excited by Substance P applied iontophoretically and in some cases this excitation was rapid. Evidence is presented for Substance P as a putative excitatory transmitter onto reticular and nigral neurones possibly released from primary sensory afferents."} {"id": "PMID:1269618", "title": "Decreased incidence of renal cell carcinoma in rats with one kidney ingesting N-4-(4'-fluorobiphenyl)acetamide.", "content": "Buffalo strain male rats, 12 weeks of age, ingesting 0.04% N-4-(4'-fluorobiphenyl)acetamide in a semisynthetic diet with both kidneys intact were more susceptible to the development of hyperplasia and carcinomas of the kidney than were rats with a uninephrectomy.", "contents": "Decreased incidence of renal cell carcinoma in rats with one kidney ingesting N-4-(4'-fluorobiphenyl)acetamide. Buffalo strain male rats, 12 weeks of age, ingesting 0.04% N-4-(4'-fluorobiphenyl)acetamide in a semisynthetic diet with both kidneys intact were more susceptible to the development of hyperplasia and carcinomas of the kidney than were rats with a uninephrectomy."} {"id": "PMID:1269619", "title": "Uptake of L-glutamate and L-aspartate in neurones and glial cells of cultured human and rat spinal cord.", "content": "Autoradiographic investigations on the uptake of L-glutamate and L-aspartate have shown that the amino acids were taken up by neurones as well as by glial cells of cultured human and rat spinal cord. The activity of glutamate and aspartate varied considerably between individual neurones, whereas glial cells showed a more even distribution of the labelled amino acids. Our results suggest that both neurones and glial cells are involved in the uptake of amino acid transmitters.", "contents": "Uptake of L-glutamate and L-aspartate in neurones and glial cells of cultured human and rat spinal cord. Autoradiographic investigations on the uptake of L-glutamate and L-aspartate have shown that the amino acids were taken up by neurones as well as by glial cells of cultured human and rat spinal cord. The activity of glutamate and aspartate varied considerably between individual neurones, whereas glial cells showed a more even distribution of the labelled amino acids. Our results suggest that both neurones and glial cells are involved in the uptake of amino acid transmitters."} {"id": "PMID:1269620", "title": "Deciduoma formation in rats with cornified vagina.", "content": "In female rats given a single injection of 1.25 mg 5 alpha-dihydrotestosterone during neonatal life, reactivity of the vaginal mucosa to hormones was permanently altered, so that the rats, when adult, could show vaginal cornification under the hormonic conditions supportive of development of deciduomata in the uterus.", "contents": "Deciduoma formation in rats with cornified vagina. In female rats given a single injection of 1.25 mg 5 alpha-dihydrotestosterone during neonatal life, reactivity of the vaginal mucosa to hormones was permanently altered, so that the rats, when adult, could show vaginal cornification under the hormonic conditions supportive of development of deciduomata in the uterus."} {"id": "PMID:1269621", "title": "Intrauterine device increases the fibrinolytic activity of the rat endometrium at deciduation, a new aspect of its contraceptive effect.", "content": "The fibrinolytic activity of the endometrium of the two uterine horns in the rat was histochemically determined. One of the horns contained a plastic-IUD, the other served as control. The endometrium of the control horn was almost inactive in contrast with that of the IUD-horn in which fibrinolytic activity was apparent. The fibrinolytic activity induced by the IUD might be involved in the prevention of ova implantation.", "contents": "Intrauterine device increases the fibrinolytic activity of the rat endometrium at deciduation, a new aspect of its contraceptive effect. The fibrinolytic activity of the endometrium of the two uterine horns in the rat was histochemically determined. One of the horns contained a plastic-IUD, the other served as control. The endometrium of the control horn was almost inactive in contrast with that of the IUD-horn in which fibrinolytic activity was apparent. The fibrinolytic activity induced by the IUD might be involved in the prevention of ova implantation."} {"id": "PMID:1269622", "title": "[Neurosecretion and hydroelectrolytic regulation in Artemia salina (author's transl)].", "content": "The activity of Artemia protocerebral median neurosecretory cells is stimulated when animals are grown in media whose tonicity is lower than that of sea weater. The substance liberated by these cells could regulate the tonicity of the internal medium.", "contents": "[Neurosecretion and hydroelectrolytic regulation in Artemia salina (author's transl)]. The activity of Artemia protocerebral median neurosecretory cells is stimulated when animals are grown in media whose tonicity is lower than that of sea weater. The substance liberated by these cells could regulate the tonicity of the internal medium."} {"id": "PMID:1269623", "title": "Host immune rejection of TA3 ascites carcinoma cells following administration of a water soluble carbodiimide.", "content": "Regression of TA3 ascites carcinoma tumors occurred following i.p. injection of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide-HC1. An immunological mechanism of drug action was indicated by the fact that no significant antitumor activity was demonstrable in mice that had previously received an immunosuppressive 700 rad dose of 60Co radiation.", "contents": "Host immune rejection of TA3 ascites carcinoma cells following administration of a water soluble carbodiimide. Regression of TA3 ascites carcinoma tumors occurred following i.p. injection of 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide-HC1. An immunological mechanism of drug action was indicated by the fact that no significant antitumor activity was demonstrable in mice that had previously received an immunosuppressive 700 rad dose of 60Co radiation."} {"id": "PMID:1269625", "title": "Concentration of \"available\" unesterified cholesterol in human plasma as evaluated from inhibition of hemolysis by lucensomycin.", "content": "The unesterified cholesterol content of plasma samples can be evaluated from the extent of inhibition of lucensomycin-induced hemolysis. The test measures, however, only the fraction of cholesterol which is available for interaction with lucensomycin, this availability being adversely affected by high phospholipid-cholesterol ratios.", "contents": "Concentration of \"available\" unesterified cholesterol in human plasma as evaluated from inhibition of hemolysis by lucensomycin. The unesterified cholesterol content of plasma samples can be evaluated from the extent of inhibition of lucensomycin-induced hemolysis. The test measures, however, only the fraction of cholesterol which is available for interaction with lucensomycin, this availability being adversely affected by high phospholipid-cholesterol ratios."} {"id": "PMID:1269626", "title": "[Structure-activity relationship of human calcitonin. III. Biological activity of synthetic analogues with shortened or terminally modified peptide chains (author's transl)].", "content": "Assays of 8 synthetic analogues of human calcitonin in rats showed that their hypocalcaemic activity was drastically reduced by deletion of the C-terminal amide group, chain-shortening or opening of the disulphide ring, but unaffected or enhanced by modification of the N-terminal amino group.", "contents": "[Structure-activity relationship of human calcitonin. III. Biological activity of synthetic analogues with shortened or terminally modified peptide chains (author's transl)]. Assays of 8 synthetic analogues of human calcitonin in rats showed that their hypocalcaemic activity was drastically reduced by deletion of the C-terminal amide group, chain-shortening or opening of the disulphide ring, but unaffected or enhanced by modification of the N-terminal amino group."} {"id": "PMID:1269627", "title": "Epilepsy in women. Oestrogen and progesterone plasma levels.", "content": "Comparison is made between numbers of fits and estrogen, progesterone plasma values during the menstrual cycle of women with epilepsy. All six cycles in women with ovulation had a significant positive correlation between estrogen/progesterone ratio and scores of fits. Three periods without ovulation all showed a significant correlation to estrogen variations.", "contents": "Epilepsy in women. Oestrogen and progesterone plasma levels. Comparison is made between numbers of fits and estrogen, progesterone plasma values during the menstrual cycle of women with epilepsy. All six cycles in women with ovulation had a significant positive correlation between estrogen/progesterone ratio and scores of fits. Three periods without ovulation all showed a significant correlation to estrogen variations."} {"id": "PMID:1269628", "title": "A method for automatic recording of serum lysozyme activity with the fragiligraph.", "content": "A quick and simple method for the estimation of lysozyme activity using the Fragiligraph, was described. Diminution of turbidity in a suspension of Micrococcus lysodeikticus produced by the addition of standard lysozyme (hen egg white) or serum sample, was continuously recorded for 5 min by the Fragiligraph. The normal mean serum lysozyme activity value obtained by this method is 6,80 mug/ml +/- 1.85.", "contents": "A method for automatic recording of serum lysozyme activity with the fragiligraph. A quick and simple method for the estimation of lysozyme activity using the Fragiligraph, was described. Diminution of turbidity in a suspension of Micrococcus lysodeikticus produced by the addition of standard lysozyme (hen egg white) or serum sample, was continuously recorded for 5 min by the Fragiligraph. The normal mean serum lysozyme activity value obtained by this method is 6,80 mug/ml +/- 1.85."} {"id": "PMID:1269634", "title": "Triterpenes of toxic and non-toxic taxa of Lantana camara.", "content": "The taxa of Lantana camara toxic to animals contain lantadene A lantadene B, whereas in two non-toxic taxa other triterpenes predominate. Several new triterpenes have been characterized. Contrary to earlier claims, lantadene A and to a lesser extent lantadene B are toxic when administered intraruminally to sheep.", "contents": "Triterpenes of toxic and non-toxic taxa of Lantana camara. The taxa of Lantana camara toxic to animals contain lantadene A lantadene B, whereas in two non-toxic taxa other triterpenes predominate. Several new triterpenes have been characterized. Contrary to earlier claims, lantadene A and to a lesser extent lantadene B are toxic when administered intraruminally to sheep."} {"id": "PMID:1269635", "title": "Synthesis of ovulation-inhibiting compounds; structure-activity relationship.", "content": "We describe the synthesis of some new derivatives of benzo(4, 5)cyclohepta(1, 2-b)thiophene which inhibit ovulation and the secretion of luteinizing hormone (LH) in the rat. We also describe the relationship between the structure and activity of these compounds.", "contents": "Synthesis of ovulation-inhibiting compounds; structure-activity relationship. We describe the synthesis of some new derivatives of benzo(4, 5)cyclohepta(1, 2-b)thiophene which inhibit ovulation and the secretion of luteinizing hormone (LH) in the rat. We also describe the relationship between the structure and activity of these compounds."} {"id": "PMID:1269637", "title": "Direct fluorination of carcinogenic polycylic aromatic hydrocarbons. 6-Fluorobenzo(a)pyrene.", "content": "Xenon difluoride reacts with benzo[a]pyrene(BaP) in dichloromethane solution in an open system to give 6-fluorobenzo[a]pyrene. This method constitutes a direct route to fluorine substituted carcinogenic polycyclic aromatic hydrocarbons.", "contents": "Direct fluorination of carcinogenic polycylic aromatic hydrocarbons. 6-Fluorobenzo(a)pyrene. Xenon difluoride reacts with benzo[a]pyrene(BaP) in dichloromethane solution in an open system to give 6-fluorobenzo[a]pyrene. This method constitutes a direct route to fluorine substituted carcinogenic polycyclic aromatic hydrocarbons."} {"id": "PMID:1269638", "title": "NMR-studies of triiodothyropropionic acid in ethanol-HCl.", "content": "The barrier to rotation in the N-acetyl methyl ester of the thyroxine was found to be 8.6 kcal mol-1. Previous experiments determining the barrier to rotation in triiodothyropropionic acid in HCl-ethanol were shown to be in error.", "contents": "NMR-studies of triiodothyropropionic acid in ethanol-HCl. The barrier to rotation in the N-acetyl methyl ester of the thyroxine was found to be 8.6 kcal mol-1. Previous experiments determining the barrier to rotation in triiodothyropropionic acid in HCl-ethanol were shown to be in error."} {"id": "PMID:1269639", "title": "Identification of uncommon amino acids in the lentil seed (Lens culinaris Med.).", "content": "The fraction of the free basic amino acids in the lentil seed was shown to contain gamma-hydroxyarginine, gamma-hydroxyornithine and homoarginine besides the common amino acids. Similar distribution was found in 5 varieties of lentil, with hydroxyarginine and arginine dominating. The significance of these findings with regard to chemotaxonomy and lentil consumption is discussed.", "contents": "Identification of uncommon amino acids in the lentil seed (Lens culinaris Med.). The fraction of the free basic amino acids in the lentil seed was shown to contain gamma-hydroxyarginine, gamma-hydroxyornithine and homoarginine besides the common amino acids. Similar distribution was found in 5 varieties of lentil, with hydroxyarginine and arginine dominating. The significance of these findings with regard to chemotaxonomy and lentil consumption is discussed."} {"id": "PMID:1269640", "title": "Food-induced changes in UV-absorption spectra of isolated chromatin from liver of rats under controlled feeding schedules.", "content": "We have measured the UV-spectra of liver chromatin extracted at 2 different times of day, corresponding to low or high rate of RNA synthesis from rats maintained under controlled feeding schedules. Results show that food intake does modify the UV-spectra of liver chromatin.", "contents": "Food-induced changes in UV-absorption spectra of isolated chromatin from liver of rats under controlled feeding schedules. We have measured the UV-spectra of liver chromatin extracted at 2 different times of day, corresponding to low or high rate of RNA synthesis from rats maintained under controlled feeding schedules. Results show that food intake does modify the UV-spectra of liver chromatin."} {"id": "PMID:1269642", "title": "Sterility and lethality in crosses involving two translocation heterozygotes of the Germay cockroach, Blatella germanica (L.).", "content": "Productivity in crosses involving two independent reciprocal translocations in Blattella germanica are reported. Lethal effects alone could not account for the reductions in hatch since completely unproductive crosses occurred frequently. The latter are attributed to the inability of reduced numbers of viable embryos to force open the egg case. The implications for genetic control of the joint dominant effects from embryonic trapping and translocation semisterility are discussed.", "contents": "Sterility and lethality in crosses involving two translocation heterozygotes of the Germay cockroach, Blatella germanica (L.). Productivity in crosses involving two independent reciprocal translocations in Blattella germanica are reported. Lethal effects alone could not account for the reductions in hatch since completely unproductive crosses occurred frequently. The latter are attributed to the inability of reduced numbers of viable embryos to force open the egg case. The implications for genetic control of the joint dominant effects from embryonic trapping and translocation semisterility are discussed."} {"id": "PMID:1269643", "title": "Differential effects of lipids on the osmotic fragility of lysosomes.", "content": "The effect of a wide range of concentrations of oleic acid, oleyl alcohol and oleic acid methyl ester on lysosomal stability has been studied under both hypotonic and isoosmotic medium conditions. Both oleic acid and oleyl alcohol exhibited a biphasic interaction pattern with lysosomes; stabilizing at low concentrations and labilizing at high concentrations. Lysosome labilization by the ester required an initial lag period.", "contents": "Differential effects of lipids on the osmotic fragility of lysosomes. The effect of a wide range of concentrations of oleic acid, oleyl alcohol and oleic acid methyl ester on lysosomal stability has been studied under both hypotonic and isoosmotic medium conditions. Both oleic acid and oleyl alcohol exhibited a biphasic interaction pattern with lysosomes; stabilizing at low concentrations and labilizing at high concentrations. Lysosome labilization by the ester required an initial lag period."} {"id": "PMID:1269644", "title": "Isolation of a Soldado-like virus (Hughes group) from Ornithodorus maritimus ticks in Ireland.", "content": "Three isolations of a virus of the Hughes group were obtained from seabird ectoparasites, Ornithodoros (Alectorobius) maritimus, on Great Saltee Island, Ireland. The agent is closely related to Soldado virsu, originally obtained from related ticks near Trinidad, West Indies, and represents the second recorded tickborne arbovirus in Ireland.", "contents": "Isolation of a Soldado-like virus (Hughes group) from Ornithodorus maritimus ticks in Ireland. Three isolations of a virus of the Hughes group were obtained from seabird ectoparasites, Ornithodoros (Alectorobius) maritimus, on Great Saltee Island, Ireland. The agent is closely related to Soldado virsu, originally obtained from related ticks near Trinidad, West Indies, and represents the second recorded tickborne arbovirus in Ireland."} {"id": "PMID:1269645", "title": "Adsorption of hepatitis B surface antigen to matrix-boudn long chain hydrocarbon structures.", "content": "The binding of hepatitis B surface antigen (HBSAg) to various matrix bound long-chain hydrocarbon structures has been studied. It was found that HBSAg was strongly bound to straight hydrocarbon chains with more than seven carbon atoms. The adsorbents can probably be used for removal and/or detection of hepatitis B infectious material.", "contents": "Adsorption of hepatitis B surface antigen to matrix-boudn long chain hydrocarbon structures. The binding of hepatitis B surface antigen (HBSAg) to various matrix bound long-chain hydrocarbon structures has been studied. It was found that HBSAg was strongly bound to straight hydrocarbon chains with more than seven carbon atoms. The adsorbents can probably be used for removal and/or detection of hepatitis B infectious material."} {"id": "PMID:1269646", "title": "In vitro attachment of trypanosomes to plastic.", "content": "Description of an in vitro system for the study of the attachment of trypanosomes to polystyrene flasks by means of hemidesmosomes. This type of attachment, whose significance is so far unknown, reproduces a natural stage in the life cycle of medically important trypanosomatid flagellates in their vector.", "contents": "In vitro attachment of trypanosomes to plastic. Description of an in vitro system for the study of the attachment of trypanosomes to polystyrene flasks by means of hemidesmosomes. This type of attachment, whose significance is so far unknown, reproduces a natural stage in the life cycle of medically important trypanosomatid flagellates in their vector."} {"id": "PMID:1269647", "title": "Nematidical activity of secondary and tertiary alkyl amides and amines.", "content": "Several C11 to C15 amides and amines that disrupt growth in certain insects showed high nematicidal activity in direct contact tests. Two amides and 9 amines killed Panagrellus at 5-10 ppm. Of these, 1 amide and 3 amines killed Meloidogyne larvae at 20 ppm.", "contents": "Nematidical activity of secondary and tertiary alkyl amides and amines. Several C11 to C15 amides and amines that disrupt growth in certain insects showed high nematicidal activity in direct contact tests. Two amides and 9 amines killed Panagrellus at 5-10 ppm. Of these, 1 amide and 3 amines killed Meloidogyne larvae at 20 ppm."} {"id": "PMID:1269648", "title": "Trinucleate pollen in the genus Populus.", "content": "It is shown by light microscopy and microspectrophotometry that several Populus species produce trinucleate pollen. Such pollen seems more widespread than previously acknowledged.", "contents": "Trinucleate pollen in the genus Populus. It is shown by light microscopy and microspectrophotometry that several Populus species produce trinucleate pollen. Such pollen seems more widespread than previously acknowledged."} {"id": "PMID:1269649", "title": "The suppression of mouse spontaneous locomotor activity by the ingestion of deuterium oxide.", "content": "The spontaneous locomotor activity of the laboratory mouse is significantly depressed by the ingestion of deuterium oxide. The response, which is reversible, is a retilinear one with up to 70% reduction in activity with the administration of 25% heavy water.", "contents": "The suppression of mouse spontaneous locomotor activity by the ingestion of deuterium oxide. The spontaneous locomotor activity of the laboratory mouse is significantly depressed by the ingestion of deuterium oxide. The response, which is reversible, is a retilinear one with up to 70% reduction in activity with the administration of 25% heavy water."} {"id": "PMID:1269650", "title": "Is glucagon involved in cold acclimatization?", "content": "Cold acclimatization in rats at 5 degrees C for 2 weeks caused a significant elevation of plasma glucagon concentration, accompanied by increased plasma FFA and glucose levels. Acute cold exposure at 5 degrees C for 5 or 60 min did not affect these parameters in plasma.", "contents": "Is glucagon involved in cold acclimatization? Cold acclimatization in rats at 5 degrees C for 2 weeks caused a significant elevation of plasma glucagon concentration, accompanied by increased plasma FFA and glucose levels. Acute cold exposure at 5 degrees C for 5 or 60 min did not affect these parameters in plasma."} {"id": "PMID:1269652", "title": "Increased erythrocyte permeability to Li and Na in the spontaneously hypertensive rat.", "content": "Red blood cells incubated in a physiological medium in which Li replaces Na (LiPSS) gain Li in exchange for Na and K. The rate of Li uptake is modestly but significantly increased in the spontaneously hypertensive rat (SHR) at 37 degrees C and at 22 degrees C. The slow rate of Na gain and K loss during cooling at 2 degrees C was about doubled in unmodified whole blood samples from the SHR.", "contents": "Increased erythrocyte permeability to Li and Na in the spontaneously hypertensive rat. Red blood cells incubated in a physiological medium in which Li replaces Na (LiPSS) gain Li in exchange for Na and K. The rate of Li uptake is modestly but significantly increased in the spontaneously hypertensive rat (SHR) at 37 degrees C and at 22 degrees C. The slow rate of Na gain and K loss during cooling at 2 degrees C was about doubled in unmodified whole blood samples from the SHR."} {"id": "PMID:1269653", "title": "Carotid chemoreceptor influence on the cardiac sympathetic nerve discharge.", "content": "Pure stimulation of carotid chemoreceptors induces, as a primary effect, the general spontaneous activation of both the cardioexcitatory and the cardioinhibitory medullary centres. These effects have been shown by keeping constant those parameters which, when modified, produced secondary effects hiding the investigated primary ones.", "contents": "Carotid chemoreceptor influence on the cardiac sympathetic nerve discharge. Pure stimulation of carotid chemoreceptors induces, as a primary effect, the general spontaneous activation of both the cardioexcitatory and the cardioinhibitory medullary centres. These effects have been shown by keeping constant those parameters which, when modified, produced secondary effects hiding the investigated primary ones."} {"id": "PMID:1269655", "title": "Hypoxia increases potassium efflux from mammalian myocardium.", "content": "Hypoxia with or without simultaneous depletion of extracellular glucose increases 42K-efflux in cat and guinea-pig papillary muscles and bovine Purkinje fibres. The change observed in K efflux may be the result of an increase in K conductance at rest.", "contents": "Hypoxia increases potassium efflux from mammalian myocardium. Hypoxia with or without simultaneous depletion of extracellular glucose increases 42K-efflux in cat and guinea-pig papillary muscles and bovine Purkinje fibres. The change observed in K efflux may be the result of an increase in K conductance at rest."} {"id": "PMID:1269657", "title": "Inhibition of ovulation in rats by antagonists to serotonin and by a new tricyclic compound.", "content": "The ovulation inhibiting activity in adult rats of the 5HT-antagonists cyproheptadine, mianserin and methysergide is shown. Furthermore the activity of a newly synthetized Cycloheptathiophenederivative, compound 26-921, which inhibits LH-secretion and consequently ovulation, is described.", "contents": "Inhibition of ovulation in rats by antagonists to serotonin and by a new tricyclic compound. The ovulation inhibiting activity in adult rats of the 5HT-antagonists cyproheptadine, mianserin and methysergide is shown. Furthermore the activity of a newly synthetized Cycloheptathiophenederivative, compound 26-921, which inhibits LH-secretion and consequently ovulation, is described."} {"id": "PMID:1269658", "title": "Acute toxicity of dimethylnitrosamine in the presence of inhibitors of DMN demethylase.", "content": "The LD50 of DMN was determined in groups of mice in the presence of inhibitors of DMN demethylase. Piperonyl butoxide, dibutylnitrosamine and nitrososarcosine had no effect on the acute toxicity of DMN. Diethylnitrosamine and DMN were markedly synergistic. All mice treated with 100 mg/kg diethylnitrosamine and 10.7 mg/kg DMN died. These results suggest that DMN demethylase may not be involved in the acute toxicity of DMN.", "contents": "Acute toxicity of dimethylnitrosamine in the presence of inhibitors of DMN demethylase. The LD50 of DMN was determined in groups of mice in the presence of inhibitors of DMN demethylase. Piperonyl butoxide, dibutylnitrosamine and nitrososarcosine had no effect on the acute toxicity of DMN. Diethylnitrosamine and DMN were markedly synergistic. All mice treated with 100 mg/kg diethylnitrosamine and 10.7 mg/kg DMN died. These results suggest that DMN demethylase may not be involved in the acute toxicity of DMN."} {"id": "PMID:1269660", "title": "DDT: the degradation of ring-labeled 14C-DDT to 14CO2 in the rat.", "content": "Ring fission of p, p'-DDT was studied in the rat following a single oral dose of 0.74 mg/kg (1.04 muCi) of uniformly ring-labeled 14C-DDT. Expired air was passed through a solution of ethanolamine-ethylene glycol monomethyl ether (1:2) to trap 14CO2. A total of 1.6% of the radioactivity administered was recovered in the expired air collected continually for 10 days, indicating that while degradation of the phenyl moiety is not a major route of p,p'-DDT metabolism in the rat, it is equal to the urinary excretion. Nevertheless, these results represent the most radical change accomplished in vivo of a residual insecticide yet reported in mammals.", "contents": "DDT: the degradation of ring-labeled 14C-DDT to 14CO2 in the rat. Ring fission of p, p'-DDT was studied in the rat following a single oral dose of 0.74 mg/kg (1.04 muCi) of uniformly ring-labeled 14C-DDT. Expired air was passed through a solution of ethanolamine-ethylene glycol monomethyl ether (1:2) to trap 14CO2. A total of 1.6% of the radioactivity administered was recovered in the expired air collected continually for 10 days, indicating that while degradation of the phenyl moiety is not a major route of p,p'-DDT metabolism in the rat, it is equal to the urinary excretion. Nevertheless, these results represent the most radical change accomplished in vivo of a residual insecticide yet reported in mammals."} {"id": "PMID:1269661", "title": "Ultrastructural autoradiographic study of the intracellular fixation of 3H-acrolein.", "content": "The fixation of 3H acrolein in Dunaliella bioculata was followed by means of quantitative autoradiography electron microscopy. A fixation was observed mostly in the nucleus where aldehyde linkage remained stable at least for 48 hours.", "contents": "Ultrastructural autoradiographic study of the intracellular fixation of 3H-acrolein. The fixation of 3H acrolein in Dunaliella bioculata was followed by means of quantitative autoradiography electron microscopy. A fixation was observed mostly in the nucleus where aldehyde linkage remained stable at least for 48 hours."} {"id": "PMID:1269662", "title": "Frequency of the various stages of the seminiferous epithelium in different strains of male mice.", "content": "The duration of the various development stages of the seminiferous epithelium in different strains of male mice was determined by scoring the frequency distribution in randomly selected tubule cross-sections. The results obtained show a difference in the duration of the various stages between the different strains.", "contents": "Frequency of the various stages of the seminiferous epithelium in different strains of male mice. The duration of the various development stages of the seminiferous epithelium in different strains of male mice was determined by scoring the frequency distribution in randomly selected tubule cross-sections. The results obtained show a difference in the duration of the various stages between the different strains."} {"id": "PMID:1269663", "title": "Further studies on the effect of 6-hydroxydopamine in retinal development.", "content": "Neonatal albino rats treated with 6-hydroxydopamine revealed depletion of rhodopsin and monoamine oxidase in their retinas.", "contents": "Further studies on the effect of 6-hydroxydopamine in retinal development. Neonatal albino rats treated with 6-hydroxydopamine revealed depletion of rhodopsin and monoamine oxidase in their retinas."} {"id": "PMID:1269664", "title": "Intercellular bridges of chick blastoderm studied by scanning and transmission electron microscopy.", "content": "Chick blastoderms were studied by scanning and transmission electron microscopy to identify by both methods a type of thread-like structure lying on the epiblast. The structure was identified by transmission microscopy as a long telophase bridge containing mid-body and spindle remnant. It appears to provide cytoplasmic continuity between only 2 cells.", "contents": "Intercellular bridges of chick blastoderm studied by scanning and transmission electron microscopy. Chick blastoderms were studied by scanning and transmission electron microscopy to identify by both methods a type of thread-like structure lying on the epiblast. The structure was identified by transmission microscopy as a long telophase bridge containing mid-body and spindle remnant. It appears to provide cytoplasmic continuity between only 2 cells."} {"id": "PMID:1269665", "title": "On the formation of corpus Balbiani in the ovogonia of man and guinea-pig.", "content": "Studies were conducted on the ovogonia of human embryos at the age of 33, 35 and 40 days. Myelin-like bodies in the nuclei and in the cytoplasm were observed. In other cases, the ovogonium contained 4-5 myelin-like bodies oriented round the centrioles. This is supposed to represent an early phase of corpus balbiani formation.", "contents": "On the formation of corpus Balbiani in the ovogonia of man and guinea-pig. Studies were conducted on the ovogonia of human embryos at the age of 33, 35 and 40 days. Myelin-like bodies in the nuclei and in the cytoplasm were observed. In other cases, the ovogonium contained 4-5 myelin-like bodies oriented round the centrioles. This is supposed to represent an early phase of corpus balbiani formation."} {"id": "PMID:1269666", "title": "Melanogenic melanocytes in human sebaceous glands.", "content": "Electron microscopic observations revealed for the first time a small number of active melanocytes synthesizing distinctive melanin-containing organelles (melanin granules)in the ducts and acini of human sebaceous glands.", "contents": "Melanogenic melanocytes in human sebaceous glands. Electron microscopic observations revealed for the first time a small number of active melanocytes synthesizing distinctive melanin-containing organelles (melanin granules)in the ducts and acini of human sebaceous glands."} {"id": "PMID:1269667", "title": "Utilization of ascorbic acid during post-embryonic development of chick skeletal muscle.", "content": "Ascorbic acid is utilized during the post-embryonic differentiation of skeletal muscle fibres in chick. While the fibres lose their heterogeneity with regard to ascorbic acid, they continue to exhibit differences in their metabolic rates in terms of the succinate dehydrogenase activity throughout life.", "contents": "Utilization of ascorbic acid during post-embryonic development of chick skeletal muscle. Ascorbic acid is utilized during the post-embryonic differentiation of skeletal muscle fibres in chick. While the fibres lose their heterogeneity with regard to ascorbic acid, they continue to exhibit differences in their metabolic rates in terms of the succinate dehydrogenase activity throughout life."} {"id": "PMID:1269670", "title": "Familial association in serum IgE levels.", "content": "The serum IgE levels measured by RIST correlated closely with those obtained by the single radioimmunodiffusion method. Values for husband and wife were closely related as were those between father and daughter but in contrast to previous observations no significant relationship existed between IgE levels for mother and son.", "contents": "Familial association in serum IgE levels. The serum IgE levels measured by RIST correlated closely with those obtained by the single radioimmunodiffusion method. Values for husband and wife were closely related as were those between father and daughter but in contrast to previous observations no significant relationship existed between IgE levels for mother and son."} {"id": "PMID:1269671", "title": "Production of heteroagglutinins in haemocytes of Leucophaea maderae L.", "content": "It was our purpose to study the immunological activity of circulating fluid cells in the blattoid insect Leucophaea maderae L. These cells are generically called haemocytes; after a preliminary morphological study under optical microscope, they were treated with anti-heteroagglutinins serum marked with fluorescein isothiocyanate. Thus, it was possible to show the presence of heteroagglutinins into the cytoplasm, as regards one group of haemocytes, and on the cell membrane for the second group.", "contents": "Production of heteroagglutinins in haemocytes of Leucophaea maderae L. It was our purpose to study the immunological activity of circulating fluid cells in the blattoid insect Leucophaea maderae L. These cells are generically called haemocytes; after a preliminary morphological study under optical microscope, they were treated with anti-heteroagglutinins serum marked with fluorescein isothiocyanate. Thus, it was possible to show the presence of heteroagglutinins into the cytoplasm, as regards one group of haemocytes, and on the cell membrane for the second group."} {"id": "PMID:1269672", "title": "Alpha adrenergic control of growth hormone in adult male rats.", "content": "Intravenous injection of 0.1 mg/kg clonidine into rats under urethane anaesthesia induced a prompt and long-lasting release of growth hormone, estimated by radioimmunoassay (IRGH), which could be abolished by 0.2 mg/kg phentolamine given into the 3rd ventricle. Injection of 3 mug/kg clonidine into the 3rd ventricle stimulated also the release of IRGH significantly. Intravenous administration of 0.32 mg/kg phenylephrine caused a small and transient release of IRGH only. These results provide evidence that central alpha-adrenergic stimulation resulting in an increased GH secretion is one important mechanism in the regulation of this hormone in the rat.", "contents": "Alpha adrenergic control of growth hormone in adult male rats. Intravenous injection of 0.1 mg/kg clonidine into rats under urethane anaesthesia induced a prompt and long-lasting release of growth hormone, estimated by radioimmunoassay (IRGH), which could be abolished by 0.2 mg/kg phentolamine given into the 3rd ventricle. Injection of 3 mug/kg clonidine into the 3rd ventricle stimulated also the release of IRGH significantly. Intravenous administration of 0.32 mg/kg phenylephrine caused a small and transient release of IRGH only. These results provide evidence that central alpha-adrenergic stimulation resulting in an increased GH secretion is one important mechanism in the regulation of this hormone in the rat."} {"id": "PMID:1269673", "title": "A preparation for the study of muscle metabolism during rest and activity.", "content": "A method for the investigation of metabolism in the isolated rat extensor digitorum longus muscle has been described. This muscle was shown to be suitable for investigations of skeletal muscle metabolism during rest and activity.", "contents": "A preparation for the study of muscle metabolism during rest and activity. A method for the investigation of metabolism in the isolated rat extensor digitorum longus muscle has been described. This muscle was shown to be suitable for investigations of skeletal muscle metabolism during rest and activity."} {"id": "PMID:1269681", "title": "Abortion need and services in the United States, 1974-1975.", "content": "More than one million legal abortions were performed in the United States last year--but one-half to three-quarters of a million women in need of abortion services were still unable to obtain them. Ninety percent of all abortions are now performed in the woman's home state, but services are still highly concentrated within states--typically in one or two metropolitan centers where most services are provided by nonhospital clinics. Only one-fourth of hospitals-and fewer than one-fifth of public hospitals-provide any abortion services. Many poor, rural and teenage women who can least afford to travel to obtain legal abortions will continue to be denied access to the services they want and need.", "contents": "Abortion need and services in the United States, 1974-1975. More than one million legal abortions were performed in the United States last year--but one-half to three-quarters of a million women in need of abortion services were still unable to obtain them. Ninety percent of all abortions are now performed in the woman's home state, but services are still highly concentrated within states--typically in one or two metropolitan centers where most services are provided by nonhospital clinics. Only one-fourth of hospitals-and fewer than one-fifth of public hospitals-provide any abortion services. Many poor, rural and teenage women who can least afford to travel to obtain legal abortions will continue to be denied access to the services they want and need."} {"id": "PMID:1269686", "title": "Successful use of the diaphragm and jelly by a young population: report of a clinical study.", "content": "In the largest contemporary study of diaphragm use in the United States, the authors examine the experience of 2,168 women who selected this method of contraception at the Margaret Sanger Research Bureau over a recent two-year period. Eight in 10 of the study group were younger than 30 years and three in 10 were aged 21-24. Seven in 10 had never been married and the same proportion had never been pregnant. Accidental pregnancies in the first 12 months of use ranged from a low of 1.9 per 100 users younger than 18 years old to a high of 3.0 among 30-34-year-olds; and more than eight in 10 were still using the diaphragm at the year's end. These rates compare favorably with those reported for the pill and IUD in other clinical studies.", "contents": "Successful use of the diaphragm and jelly by a young population: report of a clinical study. In the largest contemporary study of diaphragm use in the United States, the authors examine the experience of 2,168 women who selected this method of contraception at the Margaret Sanger Research Bureau over a recent two-year period. Eight in 10 of the study group were younger than 30 years and three in 10 were aged 21-24. Seven in 10 had never been married and the same proportion had never been pregnant. Accidental pregnancies in the first 12 months of use ranged from a low of 1.9 per 100 users younger than 18 years old to a high of 3.0 among 30-34-year-olds; and more than eight in 10 were still using the diaphragm at the year's end. These rates compare favorably with those reported for the pill and IUD in other clinical studies."} {"id": "PMID:1269735", "title": "[Pharmacological study of a series of indandione derivatives proposed as anti-inflammatory agents].", "content": "A variety of aryl-indandiones were tested in rats and mice with the aim of separating the antiinflammatory activity from anticoagulant and ulcerogenic activity. Previously reported antiinflammatory activity was confirmed. All compounds also inhibit blood coagulation. However, compounds (II) and (IV) did not show ulcerogenic activity.", "contents": "[Pharmacological study of a series of indandione derivatives proposed as anti-inflammatory agents]. A variety of aryl-indandiones were tested in rats and mice with the aim of separating the antiinflammatory activity from anticoagulant and ulcerogenic activity. Previously reported antiinflammatory activity was confirmed. All compounds also inhibit blood coagulation. However, compounds (II) and (IV) did not show ulcerogenic activity."} {"id": "PMID:1269736", "title": "[Preparation of some pyrido (2,3-e)-1,4-diazepines].", "content": "By treating pyrido (2,3-e)-1,4-diazepinones with alkyl halides, N4-alkylpyrido (2,3-e)-1,4-diazepines were obtained. In addition a number of N1-alkylpyrido (2,3-e)-1,4-diazepines were prepared from alkyltetrahydronaphthyridinones by the Schmidt reaction. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.", "contents": "[Preparation of some pyrido (2,3-e)-1,4-diazepines]. By treating pyrido (2,3-e)-1,4-diazepinones with alkyl halides, N4-alkylpyrido (2,3-e)-1,4-diazepines were obtained. In addition a number of N1-alkylpyrido (2,3-e)-1,4-diazepines were prepared from alkyltetrahydronaphthyridinones by the Schmidt reaction. Preliminary pharmacological screening of some of these compounds showed no appreciable activity."} {"id": "PMID:1269737", "title": "[Phytotoxicity of hydrazones of aromatic aldehydes].", "content": "A series of hydrazones of aromatic aldehydes (B) was prepared and tested for phytotoxicity. These compounds are bioisosters of 1-aryltriazenes (A) which were found to possess interesting phytotoxic properties in a previous research. The substances studied (Tables I leads to III: compounds(I leads to CLXXX)) some of which were previously unrecorded, were prepared by the usual procedures from the required aldehyde and hydrazine derivative. The phytotoxicity of all the compounds was studied using seven representative species in both pre- and post-emergence tests at a dose of 6 kg/ha. It was found that this class of compounds shows phytotoxicity by absorption through the foliage with specificity for Amaranthus retroflexus L. The only exceptions are compounds where the aryl residue is 2,6-dichlorophenyl; these compounds show wide spectrum of phytotoxicity by absorption through the leaves.", "contents": "[Phytotoxicity of hydrazones of aromatic aldehydes]. A series of hydrazones of aromatic aldehydes (B) was prepared and tested for phytotoxicity. These compounds are bioisosters of 1-aryltriazenes (A) which were found to possess interesting phytotoxic properties in a previous research. The substances studied (Tables I leads to III: compounds(I leads to CLXXX)) some of which were previously unrecorded, were prepared by the usual procedures from the required aldehyde and hydrazine derivative. The phytotoxicity of all the compounds was studied using seven representative species in both pre- and post-emergence tests at a dose of 6 kg/ha. It was found that this class of compounds shows phytotoxicity by absorption through the foliage with specificity for Amaranthus retroflexus L. The only exceptions are compounds where the aryl residue is 2,6-dichlorophenyl; these compounds show wide spectrum of phytotoxicity by absorption through the leaves."} {"id": "PMID:1269738", "title": "[Phytotoxic activity of triazene derivatives. VI. 1-aryl-3-arylalkyl-3-alkyltriazene derivatives].", "content": "A series of of 1-aryl-3-arylalkyl-3-alkyltriazenes (B) was prepared and studied for phytotoxic activity. The previously unknown substances [Table I: substances (I leads to XVI)] were prepared by condensation of the appropriate diazonium salt with the required secondary amine in an alkaline medium and were tested against five representative plant species in both pre- and post-emergence tests at a dose of 6 kg/ha. All the substances studied were inactive in pre-emergence tests. However most of the compounds showed phytotoxic activity by absorption through the foliage. This activity was not very pronounced and always lower than triazene analogs previously studied (type A compounds) which have no aralkyl residue on nitrogen 3.", "contents": "[Phytotoxic activity of triazene derivatives. VI. 1-aryl-3-arylalkyl-3-alkyltriazene derivatives]. A series of of 1-aryl-3-arylalkyl-3-alkyltriazenes (B) was prepared and studied for phytotoxic activity. The previously unknown substances [Table I: substances (I leads to XVI)] were prepared by condensation of the appropriate diazonium salt with the required secondary amine in an alkaline medium and were tested against five representative plant species in both pre- and post-emergence tests at a dose of 6 kg/ha. All the substances studied were inactive in pre-emergence tests. However most of the compounds showed phytotoxic activity by absorption through the foliage. This activity was not very pronounced and always lower than triazene analogs previously studied (type A compounds) which have no aralkyl residue on nitrogen 3."} {"id": "PMID:1269739", "title": "Radiopaque contrast media. XXXIV - Derivatives of omega-(3-amino-2,4,6-triiodophenoxy)alkoxyalkanoic acids.", "content": "A series of new oral cholecystographic contrast media with promising characteristics is obtained after the study of the relationships among molecular structure, tolerability, biliary and urinary excretion, as well as gallbladder opacification. The synthesis of this series is described. Particularly good tolerability, high biliary excretion and excellent roentgenographic findings were achieved with compound (IX) (iopronic acid). This contrast agent was selected for a more detailed study of toxicology, pharmaco-kinetics, metabolism and experimental radiology.", "contents": "Radiopaque contrast media. XXXIV - Derivatives of omega-(3-amino-2,4,6-triiodophenoxy)alkoxyalkanoic acids. A series of new oral cholecystographic contrast media with promising characteristics is obtained after the study of the relationships among molecular structure, tolerability, biliary and urinary excretion, as well as gallbladder opacification. The synthesis of this series is described. Particularly good tolerability, high biliary excretion and excellent roentgenographic findings were achieved with compound (IX) (iopronic acid). This contrast agent was selected for a more detailed study of toxicology, pharmaco-kinetics, metabolism and experimental radiology."} {"id": "PMID:1269740", "title": "[Negative geotropic effect and phytotoxicity of N-quinolinphthalamic acids and allied substances].", "content": "N-Quinolinphthalamic acids and allied substances have been prepared and studied for negative geotropic effect and phytotoxic activity. The substances (Tables I leads to III) prepared by fusion of the required anhydride and amine were tested to evaluate the negative geotropic effect on germinating roots of Lens esculenta Moench s.1. and phytotoxicity in both pre- and post-emergence tests against five representative weed species at a dose of 6 kg/ha. It was found that substances (I), (VII), (VIII) and (IX) showed negative geotropic effect of the same order of magnitude as that of the reference substance (alpha-naphthylphthalamic acid). Substances (VII), (VIII) and (IX) proved highly active in the phytotoxicity tests. The simultaneous appearance of geotropic and pre-emergence phytotoxic activity seems to be connected with the presence of an 8-quinoline residue on the amide nitrogen.", "contents": "[Negative geotropic effect and phytotoxicity of N-quinolinphthalamic acids and allied substances]. N-Quinolinphthalamic acids and allied substances have been prepared and studied for negative geotropic effect and phytotoxic activity. The substances (Tables I leads to III) prepared by fusion of the required anhydride and amine were tested to evaluate the negative geotropic effect on germinating roots of Lens esculenta Moench s.1. and phytotoxicity in both pre- and post-emergence tests against five representative weed species at a dose of 6 kg/ha. It was found that substances (I), (VII), (VIII) and (IX) showed negative geotropic effect of the same order of magnitude as that of the reference substance (alpha-naphthylphthalamic acid). Substances (VII), (VIII) and (IX) proved highly active in the phytotoxicity tests. The simultaneous appearance of geotropic and pre-emergence phytotoxic activity seems to be connected with the presence of an 8-quinoline residue on the amide nitrogen."} {"id": "PMID:1269741", "title": "[Adrenergic reactivity of the gastro-intestinal tract. II. Colon of the guinea pig and cecum of the mice].", "content": "A study has been made of the alpha- and beta-adrenoreceptors in the guinea pig colon and the mouse caecum using noradrenalina as agonist and alpha- and beta-adrenolytics separately or together. In the guinea pig colon alpha-adrenolytics used alone did not alter the action of noradrenalin: one beta-lytic (propranolol) used alone has slight non dose-dependent action. The alpha-lytics used together with beta-lytic strongly potential their effect. These results are interpreted as indicating that the preparation contains alpha-receptors as well as beta-receptors; activation of the alpha-receptors is observed only when the beta-mimetic effect of noradrenalin is inhibited. In the mouse caecum alpha-lytics prove devoid of effect either alone or when associated with beta-lytics; it is deduced therefore that this preparation contains only beta-receptors.", "contents": "[Adrenergic reactivity of the gastro-intestinal tract. II. Colon of the guinea pig and cecum of the mice]. A study has been made of the alpha- and beta-adrenoreceptors in the guinea pig colon and the mouse caecum using noradrenalina as agonist and alpha- and beta-adrenolytics separately or together. In the guinea pig colon alpha-adrenolytics used alone did not alter the action of noradrenalin: one beta-lytic (propranolol) used alone has slight non dose-dependent action. The alpha-lytics used together with beta-lytic strongly potential their effect. These results are interpreted as indicating that the preparation contains alpha-receptors as well as beta-receptors; activation of the alpha-receptors is observed only when the beta-mimetic effect of noradrenalin is inhibited. In the mouse caecum alpha-lytics prove devoid of effect either alone or when associated with beta-lytics; it is deduced therefore that this preparation contains only beta-receptors."} {"id": "PMID:1269742", "title": "Physiological disposition of a new diuretic compound, 2-phenyl-6-sulfonamido-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone (M.G. 13054 - fenquizone), in the dog.", "content": "The absorption, excretion and metabolism of a new diuretic compound, 2-phenyl-6-sulfonamido-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone (M.G. 13054), after oral administration to the dog have been studied. The results can be summarized as follows: 1) M.G. 13054 given orally to dogs is quickly absorbed. 2) The maximal blood levels are reached within the 3rd hour after the administration and remain appreciable (10% of the maximal values) till the 12th hour. 3) Fecal and urinary excretion is rapid and 94% of the product administered is excreted in the first 48 hours following treatment. 4) The product does not seem to be tightly bound to plasma proteins. 5) M. G. 13054 does not seem to be metabolized to any appreciable extent.", "contents": "Physiological disposition of a new diuretic compound, 2-phenyl-6-sulfonamido-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone (M.G. 13054 - fenquizone), in the dog. The absorption, excretion and metabolism of a new diuretic compound, 2-phenyl-6-sulfonamido-7-chloro-1,2,3,4-tetrahydro-4-quinazolinone (M.G. 13054), after oral administration to the dog have been studied. The results can be summarized as follows: 1) M.G. 13054 given orally to dogs is quickly absorbed. 2) The maximal blood levels are reached within the 3rd hour after the administration and remain appreciable (10% of the maximal values) till the 12th hour. 3) Fecal and urinary excretion is rapid and 94% of the product administered is excreted in the first 48 hours following treatment. 4) The product does not seem to be tightly bound to plasma proteins. 5) M. G. 13054 does not seem to be metabolized to any appreciable extent."} {"id": "PMID:1269743", "title": "[Synthesis of long chain alkyne and alkene ketoalcohols and their derivatives].", "content": "A description is given of the synthesis of the acetylenic alcohol with 16 carbon atoms (V) starting from 6-ethylendioxy-4,4-dimethyl-2-heptyne (III) and valeraldehyde followed by reduction with Raney-nickel and lithium in liquid ammonia.", "contents": "[Synthesis of long chain alkyne and alkene ketoalcohols and their derivatives]. A description is given of the synthesis of the acetylenic alcohol with 16 carbon atoms (V) starting from 6-ethylendioxy-4,4-dimethyl-2-heptyne (III) and valeraldehyde followed by reduction with Raney-nickel and lithium in liquid ammonia."} {"id": "PMID:1269772", "title": "The structure of lymphatic capillaries in lymph formation.", "content": "The lymphatic vascular system consists of endothelial lined vessels which begin as blind-end tubes or saccules that are located within the connective tissue areas. This system serves as a one-way drainage apparatus for the removal of diffusible substances as well as plasma proteins that escape the blood capillaries. If permitted to accumulate, these escaped components would deplete the circulatory system of its plasma colloids and disrupt the balance of forces responsible for the control of fluid movement and the exchange of gases and fluids across the blood vascular wall. The lymphatic capillaries are strategically placed and anatomically constructed to permit a continuous and rapid removal of the transient interstitial fluids, plasma proteins, and cells from the interstitium. Structurally the lymphatic capillaries consist of a continuous endothelium that is extremely attenuated over major aspects of its diameter, except in the perinuclear region which bulges into the lumen. These vessels lack a continuous basal lamina and maintain a close relationship with the adjoining interstitium by way of anchoring filaments. The adjacent cells are extensively overlapped and lack adhesion devices in many areas. When electron-opaque tracers are injected intravenously (i.e., horseradish peroxidase and ferritin), subsequent electron microscopic examination of tissues reveals the presence of tracer particles within the interstitium and the lymphatic capillary lumen. These particles gain access into the lymphatic capillaries via two major pathways: 1) the intercellular clefts of patent junctions and 2) plasmalemmal vesicles (pinocytotic vesicles). Another salient feature of the lymphatic endothelial cell includes the presence of numerous cytoplasmic filaments, which are similar in morphology to the actin filaments observed in a variety of cell types. The ultrastructural features of the lymphatic capillaries are discussed in relation to their role in the removal of interstitial fluids and particulate matter, and in the formation of lymph.", "contents": "The structure of lymphatic capillaries in lymph formation. The lymphatic vascular system consists of endothelial lined vessels which begin as blind-end tubes or saccules that are located within the connective tissue areas. This system serves as a one-way drainage apparatus for the removal of diffusible substances as well as plasma proteins that escape the blood capillaries. If permitted to accumulate, these escaped components would deplete the circulatory system of its plasma colloids and disrupt the balance of forces responsible for the control of fluid movement and the exchange of gases and fluids across the blood vascular wall. The lymphatic capillaries are strategically placed and anatomically constructed to permit a continuous and rapid removal of the transient interstitial fluids, plasma proteins, and cells from the interstitium. Structurally the lymphatic capillaries consist of a continuous endothelium that is extremely attenuated over major aspects of its diameter, except in the perinuclear region which bulges into the lumen. These vessels lack a continuous basal lamina and maintain a close relationship with the adjoining interstitium by way of anchoring filaments. The adjacent cells are extensively overlapped and lack adhesion devices in many areas. When electron-opaque tracers are injected intravenously (i.e., horseradish peroxidase and ferritin), subsequent electron microscopic examination of tissues reveals the presence of tracer particles within the interstitium and the lymphatic capillary lumen. These particles gain access into the lymphatic capillaries via two major pathways: 1) the intercellular clefts of patent junctions and 2) plasmalemmal vesicles (pinocytotic vesicles). Another salient feature of the lymphatic endothelial cell includes the presence of numerous cytoplasmic filaments, which are similar in morphology to the actin filaments observed in a variety of cell types. The ultrastructural features of the lymphatic capillaries are discussed in relation to their role in the removal of interstitial fluids and particulate matter, and in the formation of lymph."} {"id": "PMID:1269773", "title": "Tissue pressures and fluid dynamics in the kidney.", "content": "The kidney has several characteristics which make renal pressures and fluid dynamics unique when compared to other organs. Renal blood flow is roughly 100 times that of skeletal muscle. The renal circulation consists of two distinct capillary beds in series: a high pressure system in the glomerulus that favors filtration and a low pressure system in the peritubule network that favors reabsorption. The hydrostatic pressure in the glomerular capillary is 4-6 times higher than the hydrostatic pressure in the peritubule capillary so that approximately 25% of the plasma is filtered. The bulk of the filtrate is subsequently reabsorbed by the peritubule capillary network. Micropuncture techniques have been used to obtain quantitative measurements of the pressures and fluid dynamics of the peritubule microcirculation. The net force for uptake of all the fluid reabsorbed by a single proximal tubule up to the point of micropuncture is 21 mm Hg acting over a capillary bed with a permeability surface area product of 2 nl/min per mm Hg. In contrast to subcutaneous tissue and muscle, the renal interstitial fluid pressure is positive. The consequence of a positive interstitial fluid pressure is that normal lymph flow is relatively high and changes in interstitial fluid pressure have relatively little effects on lymph flow.", "contents": "Tissue pressures and fluid dynamics in the kidney. The kidney has several characteristics which make renal pressures and fluid dynamics unique when compared to other organs. Renal blood flow is roughly 100 times that of skeletal muscle. The renal circulation consists of two distinct capillary beds in series: a high pressure system in the glomerulus that favors filtration and a low pressure system in the peritubule network that favors reabsorption. The hydrostatic pressure in the glomerular capillary is 4-6 times higher than the hydrostatic pressure in the peritubule capillary so that approximately 25% of the plasma is filtered. The bulk of the filtrate is subsequently reabsorbed by the peritubule capillary network. Micropuncture techniques have been used to obtain quantitative measurements of the pressures and fluid dynamics of the peritubule microcirculation. The net force for uptake of all the fluid reabsorbed by a single proximal tubule up to the point of micropuncture is 21 mm Hg acting over a capillary bed with a permeability surface area product of 2 nl/min per mm Hg. In contrast to subcutaneous tissue and muscle, the renal interstitial fluid pressure is positive. The consequence of a positive interstitial fluid pressure is that normal lymph flow is relatively high and changes in interstitial fluid pressure have relatively little effects on lymph flow."} {"id": "PMID:1269776", "title": "Glycine-serine interrelations in the chick.", "content": "Glycine and serine are involved in numerous important functions in the body in addition to protein synthesis. Glycine is synthesized by higher animals; however, the rate is not adequate to support maximal growth of the chick. Studies indicate that chicks fed a glycine-serine free crystalline amino acid diet grow at approximately 80% the rate of chicks fed the same diet supplemented with glycine. An equimolar quantity of L-serine has been shown to support equal chick performance as glycine, thus indicating that serine conversion is adequate to meet the dietary need for glycine. The serine-glycine interconversion is catalyzed by the folic acid containing enzyme sering hydroxymethyltransferase, and a deficiency of this vitamin decreases the effectiveness of serine in meeting the chick's dietary need for glycine. Studies with chicks fed normal and high levels of a crystalline amino acid mixture devoid of glycine and serine indicate that the chick has the metabolic potential to synthesize more of these two amino acids than should be required for normal growth. The observed dietary response to glycine or serine or both indicates, however, that this synthetic potential is not being utilized.", "contents": "Glycine-serine interrelations in the chick. Glycine and serine are involved in numerous important functions in the body in addition to protein synthesis. Glycine is synthesized by higher animals; however, the rate is not adequate to support maximal growth of the chick. Studies indicate that chicks fed a glycine-serine free crystalline amino acid diet grow at approximately 80% the rate of chicks fed the same diet supplemented with glycine. An equimolar quantity of L-serine has been shown to support equal chick performance as glycine, thus indicating that serine conversion is adequate to meet the dietary need for glycine. The serine-glycine interconversion is catalyzed by the folic acid containing enzyme sering hydroxymethyltransferase, and a deficiency of this vitamin decreases the effectiveness of serine in meeting the chick's dietary need for glycine. Studies with chicks fed normal and high levels of a crystalline amino acid mixture devoid of glycine and serine indicate that the chick has the metabolic potential to synthesize more of these two amino acids than should be required for normal growth. The observed dietary response to glycine or serine or both indicates, however, that this synthetic potential is not being utilized."} {"id": "PMID:1269777", "title": "Nutritional and metabolic interrelationships of arginine, glutamic acid and proline in the chicken.", "content": "Proline satisfies by a narrow margin the criterion for dietary essentially for the chick. It is estimated that the chick may synthesize 80-90% of the total proline needed for growth. Although the metabolism of arginine, ornithine and glutamic acid is expected to give rise to proline, dietary supplements to these amino acids are relatively ineffective in reducing the proline requirement of chicks. Studies of the efficacy of dietary ornithine for growth, and tracer studies using L-(5-3H)arginine indicate that the conversion of ornithine to proline in vivo is limited, and the amount of proline synthesized from arginine is but a small fraction of that needed for growth. The limiting processes in proline synthesis from glutamic acid and ornithine are not known. In Escherichia coli, where the biosynthetic pathway from glutamate to proline has been elucidated, a glutamate kinase, NADP-dependent delta1-pyrroline-5-carboxylic acid (P5C) dehydrogenase and P5C reductase catalyze proline synthesis. P5C reductase is present in the soluble fraction of chicken liver and kidney. An NADP-dependent P5C dehydrogenase activity has also been observed in this fraction of liver. Further studies are required to assess the importance of these enzymes in proline biosynthesis and to determine the limiting process in proline formation in the chicken.", "contents": "Nutritional and metabolic interrelationships of arginine, glutamic acid and proline in the chicken. Proline satisfies by a narrow margin the criterion for dietary essentially for the chick. It is estimated that the chick may synthesize 80-90% of the total proline needed for growth. Although the metabolism of arginine, ornithine and glutamic acid is expected to give rise to proline, dietary supplements to these amino acids are relatively ineffective in reducing the proline requirement of chicks. Studies of the efficacy of dietary ornithine for growth, and tracer studies using L-(5-3H)arginine indicate that the conversion of ornithine to proline in vivo is limited, and the amount of proline synthesized from arginine is but a small fraction of that needed for growth. The limiting processes in proline synthesis from glutamic acid and ornithine are not known. In Escherichia coli, where the biosynthetic pathway from glutamate to proline has been elucidated, a glutamate kinase, NADP-dependent delta1-pyrroline-5-carboxylic acid (P5C) dehydrogenase and P5C reductase catalyze proline synthesis. P5C reductase is present in the soluble fraction of chicken liver and kidney. An NADP-dependent P5C dehydrogenase activity has also been observed in this fraction of liver. Further studies are required to assess the importance of these enzymes in proline biosynthesis and to determine the limiting process in proline formation in the chicken."} {"id": "PMID:1269779", "title": "Clinical experience with metiamide.", "content": "The new histamine H2-receptor antagonist, metiamide, was shown to inhibit acid and pepsin secretion in gastric secretion studies performed on patients suffering from peptic ulceration. The new drug was administered intravenously in these experiments, but effective plasma levels could also be produced by oral administration. When symptomatic patients were treated with the drug nearly all experienced marked symptomatic relief, and there was some evidence that ulcer healing occurred during treatment. When the drug was withdrawn symptoms tended to return. No toxic reactions were encountered in this trial. Double-blind studies are now being made in Britain to establish the place metiamide may have in the treatment of duodenal ulceration.", "contents": "Clinical experience with metiamide. The new histamine H2-receptor antagonist, metiamide, was shown to inhibit acid and pepsin secretion in gastric secretion studies performed on patients suffering from peptic ulceration. The new drug was administered intravenously in these experiments, but effective plasma levels could also be produced by oral administration. When symptomatic patients were treated with the drug nearly all experienced marked symptomatic relief, and there was some evidence that ulcer healing occurred during treatment. When the drug was withdrawn symptoms tended to return. No toxic reactions were encountered in this trial. Double-blind studies are now being made in Britain to establish the place metiamide may have in the treatment of duodenal ulceration."} {"id": "PMID:1269800", "title": "The luteal phase defect.", "content": "In summary, the luteal phase defect is a deficiency of corpus luteum progesterone steroidogenesis, either in amount or duration, or both. The clinical manifestations include either primary infertility or repeated first trimester abortions. The diagnosis can only be made clinically on the basis of a well-timed endometrial biopsy that is read histologically as 2 or more days out of phase with the next period in at least two cycles.", "contents": "The luteal phase defect. In summary, the luteal phase defect is a deficiency of corpus luteum progesterone steroidogenesis, either in amount or duration, or both. The clinical manifestations include either primary infertility or repeated first trimester abortions. The diagnosis can only be made clinically on the basis of a well-timed endometrial biopsy that is read histologically as 2 or more days out of phase with the next period in at least two cycles."} {"id": "PMID:1269801", "title": "Predetermination of ovulation timing by luteinizing hormone assay.", "content": "A modified rapid,solid-phase radioimmunoassay for serum luteinizing hormone requiring only 1 1/2 hours of incubation is presented. The method has been used to predetermine the time of ovulation in six infertile patients. Its advantages are presented in these cases. The simplicity and accuracy of the method make it practical, and it can serve well in the management of infertility.", "contents": "Predetermination of ovulation timing by luteinizing hormone assay. A modified rapid,solid-phase radioimmunoassay for serum luteinizing hormone requiring only 1 1/2 hours of incubation is presented. The method has been used to predetermine the time of ovulation in six infertile patients. Its advantages are presented in these cases. The simplicity and accuracy of the method make it practical, and it can serve well in the management of infertility."} {"id": "PMID:1269802", "title": "High doses of estrogens do not interfere with the ovulation-inducing effect of clomiphene citrate.", "content": "A sequential regimen of 100mg of clomiphene citrate (days 5 to 9) and 180 mug of ethynyl estradiol or 7.5 mg of conjugated estrogens (days 10 to 16 or 17) was given to 29 infertile patients. Eleven patients conceived. Four pregnancies terminated as early abortions; the remaining seven went to term. In four cases an ovarian hyperstimulation syndrome developed.", "contents": "High doses of estrogens do not interfere with the ovulation-inducing effect of clomiphene citrate. A sequential regimen of 100mg of clomiphene citrate (days 5 to 9) and 180 mug of ethynyl estradiol or 7.5 mg of conjugated estrogens (days 10 to 16 or 17) was given to 29 infertile patients. Eleven patients conceived. Four pregnancies terminated as early abortions; the remaining seven went to term. In four cases an ovarian hyperstimulation syndrome developed."} {"id": "PMID:1269803", "title": "Clomiphene-regulated ovulation for donor artificial insemination.", "content": "Seventeen couples with male-caused infertility requested donor artificial insemination between January 1, 1973, and December 31, 1974. All of the women were evaluated prior to the inseminations and were found to be ovulatory. They were treated with clomiphene, citrate 50 mg/day for 5 days beginning on day 4,5, or 6 of a menstrual cycle, and scheduled for two inseminations on the 5th and 7th days after completion of the clomiphene regimen. Fresh semen placed in cervical cups was used for the inseminations. The procedure was repeated in the following months until conception occurred.", "contents": "Clomiphene-regulated ovulation for donor artificial insemination. Seventeen couples with male-caused infertility requested donor artificial insemination between January 1, 1973, and December 31, 1974. All of the women were evaluated prior to the inseminations and were found to be ovulatory. They were treated with clomiphene, citrate 50 mg/day for 5 days beginning on day 4,5, or 6 of a menstrual cycle, and scheduled for two inseminations on the 5th and 7th days after completion of the clomiphene regimen. Fresh semen placed in cervical cups was used for the inseminations. The procedure was repeated in the following months until conception occurred."} {"id": "PMID:1269804", "title": "Presence of prolactin in human cervical mucus.", "content": "The presence of prolactin in human cervical mucus was demonstrated by radioimmunoassay. The levels of prolactin in cervical mucus were significantly higher (260 ng/ml +/- 47.5 SE) than those in sera of normally menstruating women (30.28 ng/ml +/- 2.0 SE).", "contents": "Presence of prolactin in human cervical mucus. The presence of prolactin in human cervical mucus was demonstrated by radioimmunoassay. The levels of prolactin in cervical mucus were significantly higher (260 ng/ml +/- 47.5 SE) than those in sera of normally menstruating women (30.28 ng/ml +/- 2.0 SE)."} {"id": "PMID:1269805", "title": "Antispermatozoal immunoglobulin G in the sera of subfertile men.", "content": "Sera were obtained from seven men who had not fathered a child and whose semen showed self-agglutination of spermatozoa. These samples of sera produced considerably more immobilization and agglutination of spermatozoa and positive passive hemagglutination tests than did sera from men whose semen showed less than 10% self-agglutination of spermatozoa.", "contents": "Antispermatozoal immunoglobulin G in the sera of subfertile men. Sera were obtained from seven men who had not fathered a child and whose semen showed self-agglutination of spermatozoa. These samples of sera produced considerably more immobilization and agglutination of spermatozoa and positive passive hemagglutination tests than did sera from men whose semen showed less than 10% self-agglutination of spermatozoa."} {"id": "PMID:1269806", "title": "The effect of steroid hormones on motility and selective migration of X- and Y-bearing human spermatozoa.", "content": "Motility and selective migration of X- and Y-bearing human spermatozoa were studied in the presence of physiologic levels of sex steroid hormones (17beta-estradiol; estriol, 0.5 ng/ml; testosterone; progesterone; lynestrenol; and norgestrel, 5 ng/ml) and 200-fold higher concentrations. Estrogens and, to a smaller extent, testosterone accelerated spermatozoal migration, while gestagens had an inhibitory effect. 17beta-Estradiol was most effective in stimulating the motility of human spermatozoa, while norgestrel caused the strongest inhibition of forward movement. Migration of X- and Y-bearing spermatozoa was most significantly altered after longer distances of migration, shown by an increase in the percentage of Y-bearing spermatozoa from 43.7% to 63.3% at a distance of 90 mm. However, prolongation of migration time to 36 hours caused a reduction in the percentage of Y-bearing spermatozoa at the 90-mm distance, from 63.3% to 46%. Specific differential effects of sex steroid hormones on the pattern of selective migration and the distribution of X- and Y-bearing spermatozoa were not observed.", "contents": "The effect of steroid hormones on motility and selective migration of X- and Y-bearing human spermatozoa. Motility and selective migration of X- and Y-bearing human spermatozoa were studied in the presence of physiologic levels of sex steroid hormones (17beta-estradiol; estriol, 0.5 ng/ml; testosterone; progesterone; lynestrenol; and norgestrel, 5 ng/ml) and 200-fold higher concentrations. Estrogens and, to a smaller extent, testosterone accelerated spermatozoal migration, while gestagens had an inhibitory effect. 17beta-Estradiol was most effective in stimulating the motility of human spermatozoa, while norgestrel caused the strongest inhibition of forward movement. Migration of X- and Y-bearing spermatozoa was most significantly altered after longer distances of migration, shown by an increase in the percentage of Y-bearing spermatozoa from 43.7% to 63.3% at a distance of 90 mm. However, prolongation of migration time to 36 hours caused a reduction in the percentage of Y-bearing spermatozoa at the 90-mm distance, from 63.3% to 46%. Specific differential effects of sex steroid hormones on the pattern of selective migration and the distribution of X- and Y-bearing spermatozoa were not observed."} {"id": "PMID:1269807", "title": "Changes in the sensitivity of adrenergic receptors in the oviduct during early gestation in the rabbit.", "content": "There is evidence to indicate that the transport of an egg through the rabbit oviduct is controlled through an interaction of the sympathetic nervous system and ovarian hormones. The effect of norepinephrine (NE) on the contractility of the oviduct during the first 8 days of gestation was studied using the rabbit perfused oviduct. The sensitivity of the alpha-adrenergic receptors of the oviduct to NE decreased progressively during early gestation. This was reflected in a potency change and a decrease in the maximal response obtained. These data support the concept that an isthmic sphinctering effect mediated by the autonomic nervous system may play a role in the regulation of egg transport through the oviduct. Blood pressure responses to NE did not change during early pregnancy except that the responses to NE were significantly enhanced immediately after mating. This suggests that the sensitivity changes to autonomic agents during early gestation may be selective for reproductive tissues.", "contents": "Changes in the sensitivity of adrenergic receptors in the oviduct during early gestation in the rabbit. There is evidence to indicate that the transport of an egg through the rabbit oviduct is controlled through an interaction of the sympathetic nervous system and ovarian hormones. The effect of norepinephrine (NE) on the contractility of the oviduct during the first 8 days of gestation was studied using the rabbit perfused oviduct. The sensitivity of the alpha-adrenergic receptors of the oviduct to NE decreased progressively during early gestation. This was reflected in a potency change and a decrease in the maximal response obtained. These data support the concept that an isthmic sphinctering effect mediated by the autonomic nervous system may play a role in the regulation of egg transport through the oviduct. Blood pressure responses to NE did not change during early pregnancy except that the responses to NE were significantly enhanced immediately after mating. This suggests that the sensitivity changes to autonomic agents during early gestation may be selective for reproductive tissues."} {"id": "PMID:1269808", "title": "Demonstration of postovulatory sphincter action by the isthmus of the rabbit oviduct.", "content": "Doughnut-shaped, carbon-impregnated rubber microtransducers calibrated to measure changes in diameter are used to demonstrate the occurrence of a sphincter action in the isthmus of the rabbit oviduct following human chorionic gonadotropin (HCG)-induced ovulation. The postovulatory constricture of the isthmus is temporal and coincides with the period when ova are retained in the oviduct. The mean change in diameter of transducers positioned within the lumen of the isthmus in rabbits treated with HCG are significantly different from mean changes observed in nontreated control rabbits when tested at 8-hour intervals over a 104-hour period. The difference is due to a statistically significant decrease in transducer diameter which occurs between 16 and 56 hours post-HCG injection. Treatment with exogenous estrogen in combination with HCG enhances both the magnitude and duration of this constricture. Significant differences occur between 8 and 104 hours. Pretreatment with progesterone prior to HCG-induced ovulation completely blocks the constricture of the isthmus. Both oviducts exhibit identical responses following HCG-induced ovulation. Sphincter action is not confirmed to a small localized segment of the isthmus but occurs over a wide area.", "contents": "Demonstration of postovulatory sphincter action by the isthmus of the rabbit oviduct. Doughnut-shaped, carbon-impregnated rubber microtransducers calibrated to measure changes in diameter are used to demonstrate the occurrence of a sphincter action in the isthmus of the rabbit oviduct following human chorionic gonadotropin (HCG)-induced ovulation. The postovulatory constricture of the isthmus is temporal and coincides with the period when ova are retained in the oviduct. The mean change in diameter of transducers positioned within the lumen of the isthmus in rabbits treated with HCG are significantly different from mean changes observed in nontreated control rabbits when tested at 8-hour intervals over a 104-hour period. The difference is due to a statistically significant decrease in transducer diameter which occurs between 16 and 56 hours post-HCG injection. Treatment with exogenous estrogen in combination with HCG enhances both the magnitude and duration of this constricture. Significant differences occur between 8 and 104 hours. Pretreatment with progesterone prior to HCG-induced ovulation completely blocks the constricture of the isthmus. Both oviducts exhibit identical responses following HCG-induced ovulation. Sphincter action is not confirmed to a small localized segment of the isthmus but occurs over a wide area."} {"id": "PMID:1269809", "title": "Effects of intrauterine devices on nuclear deoxyribonucleic acid metabolism in rabbit blastocysts: an autoradiographic study.", "content": "A metabolic parameter, DNA synthesis, was measured in rabbit blastocysts exposed to Silastic intrauterine devices (IUDs) and compared with those without IUD exposure. Autoradiographic detection of 3H-thymidine uptake showed that the IUD-exposed blastocysts contained fewer labeled cells than their IUD-free equivalents. The depressed DNA synthesis may be caused by either a block in the cell cycle or a block in DNA synthesis itself. Either way, the result could be consistent with the observation that embryo deaths occur at all growth stages, preimplantation, during implantation, and postimplantation.", "contents": "Effects of intrauterine devices on nuclear deoxyribonucleic acid metabolism in rabbit blastocysts: an autoradiographic study. A metabolic parameter, DNA synthesis, was measured in rabbit blastocysts exposed to Silastic intrauterine devices (IUDs) and compared with those without IUD exposure. Autoradiographic detection of 3H-thymidine uptake showed that the IUD-exposed blastocysts contained fewer labeled cells than their IUD-free equivalents. The depressed DNA synthesis may be caused by either a block in the cell cycle or a block in DNA synthesis itself. Either way, the result could be consistent with the observation that embryo deaths occur at all growth stages, preimplantation, during implantation, and postimplantation."} {"id": "PMID:1269810", "title": "The effect of centchroman on serum luteinizing hormone in normal males.", "content": "Elevation of serum luteinizing hormone levels was observed in five normal male volunteers while they were taking Centchroman. This effect resembles that of clomiphene and suggests a new biologic potential of Centchroman.", "contents": "The effect of centchroman on serum luteinizing hormone in normal males. Elevation of serum luteinizing hormone levels was observed in five normal male volunteers while they were taking Centchroman. This effect resembles that of clomiphene and suggests a new biologic potential of Centchroman."} {"id": "PMID:1269837", "title": "Differential sensitivity of glycogenolysis and gluconeogenesis to insulin infusions in dogs.", "content": "The suppressive effect of insulin on hepatic glucose production is generally recognized. Though it is well established that this effect is at least partially due to inhibition of glycogenolysis, controversy still exists about insulin's effect on gluconeogenesis. The present study was undertaken to determine whether insulin could affect gluconeogenesis from alanine in the intact dog and to compare the effect of insulin on glycogenolysis and gluconeogenesis. In anesthetized dogs fasted overnight, blood samples were drawn simultaneously from a femoral artery and hepatic vein. Alanine-U-14C, 10 mu Ci./kg., was infused over 110 minutes. A constant insulin infusion at either 1 or 5 mU./kg./min. was begun at 50 minutes, and blood glucose concentration was maintained by a variable glucose infusion. When insulin was infused at 1 mU./kg./min., resulting in plasma immunoreactive insulin (IRI) levels of 73 +/- 10 muU./ml., the net splanchnic glucose production (NSGP) was suppressed from 2.7 +/- 2 mg./kg./min. to virtually zero. In constrast, this small increment in insulin concentration had no demonstrable effect on the net splanchnic uptake of alanine or on the conversion of plasma alanine to glucose (7.9 +/- 0.3 mu mol/min.). Insulin infused at 5 mU./kg./min. resulted in IRI levels of 240 +/- 25 muU./ml. This higher insulin concentration was associated with a marked suppression of both the NSGP (100 per cent) and the conversion of plasma alanine to glucose (90 per cent) but did not affect the extraction of alanine by the splanchnic bed. Doses of both 1 and 5 mU./kg./min. were associated with a 35 per cent fall in immunoreactive glucagon levels. These data demonstrate that (1) glycogenolysis is more sensitive than gluconeogenesis to the inhibitory effect of small increments in insulin concentrations, (2) gluconeogenesis could be suppressed by insulin but only at higher insulin concentrations, (3) this suppression of gluconeogenesis from alanine by insulin was due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine, and finally, (4) that insulin can suppress glucagon in the absence of hyperglycemia.", "contents": "Differential sensitivity of glycogenolysis and gluconeogenesis to insulin infusions in dogs. The suppressive effect of insulin on hepatic glucose production is generally recognized. Though it is well established that this effect is at least partially due to inhibition of glycogenolysis, controversy still exists about insulin's effect on gluconeogenesis. The present study was undertaken to determine whether insulin could affect gluconeogenesis from alanine in the intact dog and to compare the effect of insulin on glycogenolysis and gluconeogenesis. In anesthetized dogs fasted overnight, blood samples were drawn simultaneously from a femoral artery and hepatic vein. Alanine-U-14C, 10 mu Ci./kg., was infused over 110 minutes. A constant insulin infusion at either 1 or 5 mU./kg./min. was begun at 50 minutes, and blood glucose concentration was maintained by a variable glucose infusion. When insulin was infused at 1 mU./kg./min., resulting in plasma immunoreactive insulin (IRI) levels of 73 +/- 10 muU./ml., the net splanchnic glucose production (NSGP) was suppressed from 2.7 +/- 2 mg./kg./min. to virtually zero. In constrast, this small increment in insulin concentration had no demonstrable effect on the net splanchnic uptake of alanine or on the conversion of plasma alanine to glucose (7.9 +/- 0.3 mu mol/min.). Insulin infused at 5 mU./kg./min. resulted in IRI levels of 240 +/- 25 muU./ml. This higher insulin concentration was associated with a marked suppression of both the NSGP (100 per cent) and the conversion of plasma alanine to glucose (90 per cent) but did not affect the extraction of alanine by the splanchnic bed. Doses of both 1 and 5 mU./kg./min. were associated with a 35 per cent fall in immunoreactive glucagon levels. These data demonstrate that (1) glycogenolysis is more sensitive than gluconeogenesis to the inhibitory effect of small increments in insulin concentrations, (2) gluconeogenesis could be suppressed by insulin but only at higher insulin concentrations, (3) this suppression of gluconeogenesis from alanine by insulin was due to an intrahepatic effect rather than an effect on the splanchnic extraction of alanine, and finally, (4) that insulin can suppress glucagon in the absence of hyperglycemia."} {"id": "PMID:1269838", "title": "Assessment of peripheral vascular disease in patients with diabetes. Two case studies.", "content": "This report proposes that perfusion scanning in combination with arteriography be included in the diagnostic work-up of the diabetic patient who, because of peripheral vascular complications, is a candidate for surgery. Two cases are reported which illustrate the extremes of the findings: abnormal arteriogram-normal scan indicating large-vessel disease without significant small-vessel involvement. It is suggested that these patients are candidates for vascular reconstruction. The other extreme is the normal arteriogram-abnormal scan indicating small-vessels disease without significant large-vessel involvement. It is apparent that these patients are not candidates for vascular reconstruction.", "contents": "Assessment of peripheral vascular disease in patients with diabetes. Two case studies. This report proposes that perfusion scanning in combination with arteriography be included in the diagnostic work-up of the diabetic patient who, because of peripheral vascular complications, is a candidate for surgery. Two cases are reported which illustrate the extremes of the findings: abnormal arteriogram-normal scan indicating large-vessel disease without significant small-vessel involvement. It is suggested that these patients are candidates for vascular reconstruction. The other extreme is the normal arteriogram-abnormal scan indicating small-vessels disease without significant large-vessel involvement. It is apparent that these patients are not candidates for vascular reconstruction."} {"id": "PMID:1269839", "title": "Arginine-stimulated hyperglucagonemia in diabetic Pima Indians.", "content": "Groups of 27 nondiabetic Pima Indians, 34 nondiabetic Caucasians, and 12 diabetic Pima Indians with recent onset of their disease received an arginine infusion to determine if (1) nondiabetic Pima Indians and Caucasians had a similar glucagon response to arginine and (2) diabetic Pimas had excessive glucagon response to arginine as reported in other racial groups. The fasting glucagon levels in the three groups were not significantly different. During arginine monochloride infusion (5 mg./kg./minute for 40 minutes) the diabetic Pimas had glucagon levels significantly higher at 10 minutes and at all sampling points thereafter than the normo-glycemic Pimas. Plasma insulin levels also increased during the infusion but, notably, never differed significantly between these two groups. There was no significant difference in the glucagon levels at any sampling point between the nondiabetic Pimas and Caucasians. The differences in glucagon levels between the nondiabetic and diabetic Indians are similar to those differences reported between diabetic and nondiabetic subjects of other racial origins.", "contents": "Arginine-stimulated hyperglucagonemia in diabetic Pima Indians. Groups of 27 nondiabetic Pima Indians, 34 nondiabetic Caucasians, and 12 diabetic Pima Indians with recent onset of their disease received an arginine infusion to determine if (1) nondiabetic Pima Indians and Caucasians had a similar glucagon response to arginine and (2) diabetic Pimas had excessive glucagon response to arginine as reported in other racial groups. The fasting glucagon levels in the three groups were not significantly different. During arginine monochloride infusion (5 mg./kg./minute for 40 minutes) the diabetic Pimas had glucagon levels significantly higher at 10 minutes and at all sampling points thereafter than the normo-glycemic Pimas. Plasma insulin levels also increased during the infusion but, notably, never differed significantly between these two groups. There was no significant difference in the glucagon levels at any sampling point between the nondiabetic Pimas and Caucasians. The differences in glucagon levels between the nondiabetic and diabetic Indians are similar to those differences reported between diabetic and nondiabetic subjects of other racial origins."} {"id": "PMID:1269840", "title": "Altered lysosomal glycohydrolase activities in juvenile diabetes mellitus.", "content": "Studies have been carried out on activities of lysosomal beta-N-acetylhexosaminidase (hex), beta-galactosidase (beta-gal), alpha-glucosidase (alpha-glu), and acid phosphatase (AP) in serum and urine from patients with juvenile diabetes and matched controls. There is a large increase in blood and urinary hex activity (the former presenting three distinct patterns of abnormality), a moderate increase in urinary beta-gal, and a small increase in urinary alpha-glu activity, but no elevation of blood or urinary AP in the diabetics. Urinary alpha-glu activity in the diabetics shows striking inhibition by glucose, and this may reflect a similar phenomenon in vivo. Although glycohydrolase activities are elevated in patients with no detectable microangiopathy, more striking changes may be observed in patients with severe small-vessel disease. These alterations may be associated with increased glycoprotein catabolism in the diabetic, an area in need of further studies in the human and experimental diabetic animal.", "contents": "Altered lysosomal glycohydrolase activities in juvenile diabetes mellitus. Studies have been carried out on activities of lysosomal beta-N-acetylhexosaminidase (hex), beta-galactosidase (beta-gal), alpha-glucosidase (alpha-glu), and acid phosphatase (AP) in serum and urine from patients with juvenile diabetes and matched controls. There is a large increase in blood and urinary hex activity (the former presenting three distinct patterns of abnormality), a moderate increase in urinary beta-gal, and a small increase in urinary alpha-glu activity, but no elevation of blood or urinary AP in the diabetics. Urinary alpha-glu activity in the diabetics shows striking inhibition by glucose, and this may reflect a similar phenomenon in vivo. Although glycohydrolase activities are elevated in patients with no detectable microangiopathy, more striking changes may be observed in patients with severe small-vessel disease. These alterations may be associated with increased glycoprotein catabolism in the diabetic, an area in need of further studies in the human and experimental diabetic animal."} {"id": "PMID:1269841", "title": "Insulin and growth-hormone responses in neonatal hyperglycemia.", "content": "Glucose, insulin, and growth hormone values were studied prospectively in 75 premature infants during the first five days after birth. Intravenous glucose was given at a mean rate of 4.7-4.9 mg./kg./min. (range 3-7). Mean birth weight was 1,394+/-47 gm. (mean+/-S.E.M.). Blood glucose values were significantly higher on days 1 and 2 than on days 3 to 5. Hypoglycemia (blood glucose less than 20 mg./100 ml.) occurred in two SGA and one AGA infants. On the other hand, hyperglycemia (greater than 125 mg./100 ml.) was found in 32 of the 75 (42.7 per cent) infants. A significantly greater number of deaths occurred in infants with hyperglycemia (19/32) than in those with normoglycemia (19/32) than in those with normoglycemia (5/43). Mean plasma insulin values were significantly higher on days 1 and 2 (15+/-3 and 18+/-4 muU./ml.) than on days 3 and 4-5 (6+/-1 and 7+/-2 muU./ml.). In addition, mean insulin levels were significantly higher during hyperglycemic than during normoglycemic glucose levels at similar postnatal age. Growth hormone values were higher during the first three days than subsequently, but the values were similar in normoglycemic and hyperglycemic groups. Significant negative correlations were seen between glucose values on the first two days of postnatal life and birth weight, gestational age, and Apgar scores, whereas positive correlations were found with FiO2 and respiratory distress score (RDS).", "contents": "Insulin and growth-hormone responses in neonatal hyperglycemia. Glucose, insulin, and growth hormone values were studied prospectively in 75 premature infants during the first five days after birth. Intravenous glucose was given at a mean rate of 4.7-4.9 mg./kg./min. (range 3-7). Mean birth weight was 1,394+/-47 gm. (mean+/-S.E.M.). Blood glucose values were significantly higher on days 1 and 2 than on days 3 to 5. Hypoglycemia (blood glucose less than 20 mg./100 ml.) occurred in two SGA and one AGA infants. On the other hand, hyperglycemia (greater than 125 mg./100 ml.) was found in 32 of the 75 (42.7 per cent) infants. A significantly greater number of deaths occurred in infants with hyperglycemia (19/32) than in those with normoglycemia (19/32) than in those with normoglycemia (5/43). Mean plasma insulin values were significantly higher on days 1 and 2 (15+/-3 and 18+/-4 muU./ml.) than on days 3 and 4-5 (6+/-1 and 7+/-2 muU./ml.). In addition, mean insulin levels were significantly higher during hyperglycemic than during normoglycemic glucose levels at similar postnatal age. Growth hormone values were higher during the first three days than subsequently, but the values were similar in normoglycemic and hyperglycemic groups. Significant negative correlations were seen between glucose values on the first two days of postnatal life and birth weight, gestational age, and Apgar scores, whereas positive correlations were found with FiO2 and respiratory distress score (RDS)."} {"id": "PMID:1269842", "title": "Significant muscle capillary basement membrane thickening in spontaneously diabetic Mystromys albicaudatus.", "content": "Skeletal muscle capillary basement membrane thickness was determined in age- and sex-matched normal and spontaneously diabetic Mystromys albicaudatus. In nondiabetic animals the average basement membrane thickness was 482.6+/-48.7 A as against 779.0+/-319.9 A in the diabetic ones. This difference was statistically significant at P less than 0.005.", "contents": "Significant muscle capillary basement membrane thickening in spontaneously diabetic Mystromys albicaudatus. Skeletal muscle capillary basement membrane thickness was determined in age- and sex-matched normal and spontaneously diabetic Mystromys albicaudatus. In nondiabetic animals the average basement membrane thickness was 482.6+/-48.7 A as against 779.0+/-319.9 A in the diabetic ones. This difference was statistically significant at P less than 0.005."} {"id": "PMID:1269843", "title": "Ocular palsies in children with diabetes mellitus.", "content": "The findings in three children with ocular palsies are reported in this paper. Two had insulin-requiring diabetes and one demonstrated only an abnormal I.V. glucose tolerance test. In the first patient the condition resolved in four weeks; in the second it had not fully resolved after 21 months, and in the third patient surgery was required for correction after seven months. We suggest that any child who develops a sudden ocular palsy should be examined for diabetes mellitus.", "contents": "Ocular palsies in children with diabetes mellitus. The findings in three children with ocular palsies are reported in this paper. Two had insulin-requiring diabetes and one demonstrated only an abnormal I.V. glucose tolerance test. In the first patient the condition resolved in four weeks; in the second it had not fully resolved after 21 months, and in the third patient surgery was required for correction after seven months. We suggest that any child who develops a sudden ocular palsy should be examined for diabetes mellitus."} {"id": "PMID:1269844", "title": "Effect of multiple daily insulin injections on the course of diabetic retinopathy.", "content": "Forty-two diabetic patients on insulin once a day in the early stage of diabetic retinopathy were randomly assigned to one of two kinds of insulin regimen, i.e., single or multiple daily injections. Retinal changes were quantitatively estimated by counting the microaneurysms (MAs) observed on fluorescein angiograms at the posterior pole of the more diseased eye. Baseline characteristics of the two groups were not significantly different. These included duration of diabetes, age at diagnosis, daily dose of insulin, amount of urinary sugar excreted in 24 hours, fasting blood sugar (FBS), and number of MAs. During the follow-up (mean duration of three years) the mean yearly progression in the number of MAs was significantly less in the multiple- than in the single-injection groups: 1.8 +/- 0.7 versus 7.2 +/- 1.9 (p less than 0.01; nonparametric test: p less than 0.02). Final values were, respectively, MAs: 15.2 +/- 4.9; 33.0 +/- 7.9; glycosuria (gm./24 hrs): 20.6 +/- 2.5; 27.5 +/- 4.3; FBS (mg./100 ml.): 154 +/- 15; 195 +/- 11. P values comparing the two groups were less than 0.02, less than 0.02, and less than 0.05. Thus, in this clinical trial, made under routine treatment conditions, the use of divided daily insulin injections was effective in improving diabetic control and delaying retinal changes.", "contents": "Effect of multiple daily insulin injections on the course of diabetic retinopathy. Forty-two diabetic patients on insulin once a day in the early stage of diabetic retinopathy were randomly assigned to one of two kinds of insulin regimen, i.e., single or multiple daily injections. Retinal changes were quantitatively estimated by counting the microaneurysms (MAs) observed on fluorescein angiograms at the posterior pole of the more diseased eye. Baseline characteristics of the two groups were not significantly different. These included duration of diabetes, age at diagnosis, daily dose of insulin, amount of urinary sugar excreted in 24 hours, fasting blood sugar (FBS), and number of MAs. During the follow-up (mean duration of three years) the mean yearly progression in the number of MAs was significantly less in the multiple- than in the single-injection groups: 1.8 +/- 0.7 versus 7.2 +/- 1.9 (p less than 0.01; nonparametric test: p less than 0.02). Final values were, respectively, MAs: 15.2 +/- 4.9; 33.0 +/- 7.9; glycosuria (gm./24 hrs): 20.6 +/- 2.5; 27.5 +/- 4.3; FBS (mg./100 ml.): 154 +/- 15; 195 +/- 11. P values comparing the two groups were less than 0.02, less than 0.02, and less than 0.05. Thus, in this clinical trial, made under routine treatment conditions, the use of divided daily insulin injections was effective in improving diabetic control and delaying retinal changes."} {"id": "PMID:1269845", "title": "A study of the morphological changes in the small intestine of the spontaneously diabetic Chinese hamster.", "content": "Several morphological changes were observed microscopically in the small intestine of some diabetic Chinese hamsters. Although some alterations lacked statistical significance due to variation, most diabetics displayed a greater incidence and severity compared with nondiabetic controls. The following structural deviations were seen in the small intestines of some diabetics: increased surface area, elevated number of goblet cells per villus, decreased muscle thickness with connective tissue infiltration, reduced number of Auerbach's plexuses, lymphocyte aggregations accompanied by blunted villi, blood vascular lesions and deformed villi due to excessive loss of epithelial cells.", "contents": "A study of the morphological changes in the small intestine of the spontaneously diabetic Chinese hamster. Several morphological changes were observed microscopically in the small intestine of some diabetic Chinese hamsters. Although some alterations lacked statistical significance due to variation, most diabetics displayed a greater incidence and severity compared with nondiabetic controls. The following structural deviations were seen in the small intestines of some diabetics: increased surface area, elevated number of goblet cells per villus, decreased muscle thickness with connective tissue infiltration, reduced number of Auerbach's plexuses, lymphocyte aggregations accompanied by blunted villi, blood vascular lesions and deformed villi due to excessive loss of epithelial cells."} {"id": "PMID:1269846", "title": "Pancreatic blood flow in conscious dogs after oral administration of glucose.", "content": "Dogs with electromagnetic flowprobe implanted around the superior pancreaticoduodenal artery and with an hydraulic occluder implanted upstream from the flowprobe were examined between the 3rd and the 8th postoperative day. During an oral glucose load, blood flow increased from the beginning of administration to about 25 minutes, but not when blood glucose and plasma IRI exhibit their maxima. The rise of pancreatic blood flow is assumed to be produced by reflexes similar to those stimulating insulin secretion and exocrine pancreatic function during the early phase of an oral glucose load.", "contents": "Pancreatic blood flow in conscious dogs after oral administration of glucose. Dogs with electromagnetic flowprobe implanted around the superior pancreaticoduodenal artery and with an hydraulic occluder implanted upstream from the flowprobe were examined between the 3rd and the 8th postoperative day. During an oral glucose load, blood flow increased from the beginning of administration to about 25 minutes, but not when blood glucose and plasma IRI exhibit their maxima. The rise of pancreatic blood flow is assumed to be produced by reflexes similar to those stimulating insulin secretion and exocrine pancreatic function during the early phase of an oral glucose load."} {"id": "PMID:1269847", "title": "Secretin and insulin: response to intraduodenal acid.", "content": "Immunoreactive secretin (IRS) and immunoreactive insulin (IRI) levels were measured in humans and dogs following the intraduodenal instillation of hydrochloric acid. IRS levels rose after acid in both instances, but a concomitant rise in peripheral IRI levels was not noted. Premedication of the humans with Scopolamine prevented a rise of IRS in the human subjects. It is concluded that the endovenous release of IRS alone does not result in increased IRI levels in peripheral blood and that IRS release may be under vagal control.", "contents": "Secretin and insulin: response to intraduodenal acid. Immunoreactive secretin (IRS) and immunoreactive insulin (IRI) levels were measured in humans and dogs following the intraduodenal instillation of hydrochloric acid. IRS levels rose after acid in both instances, but a concomitant rise in peripheral IRI levels was not noted. Premedication of the humans with Scopolamine prevented a rise of IRS in the human subjects. It is concluded that the endovenous release of IRS alone does not result in increased IRI levels in peripheral blood and that IRS release may be under vagal control."} {"id": "PMID:1269848", "title": "Activity of pyruvate dehydrogenase complex in the mammary gland of normal and diabetic rats.", "content": "After parturition there is a 10 fold increase in the actual and total activity of the PDH complex in the mammary gland, which can be explained by an increased amount of enzyme protein. There is a marked difference between the activity state of the PDH complex in the suckled and unsuckled gland of the same animals. In fasting rats the active form of the PDH complex is decreased. This effect is further enhanced by inhibition of suckling. In the diabetic state the PDHa activity is reduced, but the change is statistically insignificant. The decreased milk production during diabetes results from the reduction of the total mass of gland. The total activity of the PDH complex is the same in fetal and neonatal liver of the rat. Whereas the PDH complex is fully activated before parturition, there is a significant decrease in the active form of the pyruvate dehydrogenase complex in the liver of the newborn rats.", "contents": "Activity of pyruvate dehydrogenase complex in the mammary gland of normal and diabetic rats. After parturition there is a 10 fold increase in the actual and total activity of the PDH complex in the mammary gland, which can be explained by an increased amount of enzyme protein. There is a marked difference between the activity state of the PDH complex in the suckled and unsuckled gland of the same animals. In fasting rats the active form of the PDH complex is decreased. This effect is further enhanced by inhibition of suckling. In the diabetic state the PDHa activity is reduced, but the change is statistically insignificant. The decreased milk production during diabetes results from the reduction of the total mass of gland. The total activity of the PDH complex is the same in fetal and neonatal liver of the rat. Whereas the PDH complex is fully activated before parturition, there is a significant decrease in the active form of the pyruvate dehydrogenase complex in the liver of the newborn rats."} {"id": "PMID:1269849", "title": "Effect of high fat vs. high carbohydrate feeding on the development of obesity in weanling ob/ob mice.", "content": "Mice with hereditary obesity (ob/ob) were fed isocaloric, isoprotein diets with varying proportions of carbohydrate-to-fat from the time of weaning to 18 weeks of age. Body weight, plasma glucose,and plasma insulin were determined at frequent intervals; body lipid and pancreatic insulin were determined at termination. Obesity developed when only carbohydrate was provided as caloric source (and in the presence of essential fatty acid deficiency), but obesity was greatly enhanced when 5% fat was added. Obesity also developed in the absence of dietary carbohydrate, even though hyperinsulinism was significantly reduced by this regimen. It is concluded that 1) both enhanced storage of dietary fat and lipogenesis contribute to obesity, the former more so than the latter; 2) the degree of hyperinsulinism does not determine the degree of obesity; 3) the development of hyperinsulinism does not require stimulation by exogenous oral carbohydrate.", "contents": "Effect of high fat vs. high carbohydrate feeding on the development of obesity in weanling ob/ob mice. Mice with hereditary obesity (ob/ob) were fed isocaloric, isoprotein diets with varying proportions of carbohydrate-to-fat from the time of weaning to 18 weeks of age. Body weight, plasma glucose,and plasma insulin were determined at frequent intervals; body lipid and pancreatic insulin were determined at termination. Obesity developed when only carbohydrate was provided as caloric source (and in the presence of essential fatty acid deficiency), but obesity was greatly enhanced when 5% fat was added. Obesity also developed in the absence of dietary carbohydrate, even though hyperinsulinism was significantly reduced by this regimen. It is concluded that 1) both enhanced storage of dietary fat and lipogenesis contribute to obesity, the former more so than the latter; 2) the degree of hyperinsulinism does not determine the degree of obesity; 3) the development of hyperinsulinism does not require stimulation by exogenous oral carbohydrate."} {"id": "PMID:1269850", "title": "The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics.", "content": "The microvascular permeability to small and large molecules was studied during good and poor metabolic regulation in ten short duration juvenile diabetics. The following variables were measured; daily urinary albumin and beta2-microglobulin-excretion rates, whole body transcapillary escape rate of albumin (TER), glomerular filtration rate (GFR), capillary filtration coefficient (CFC), and capillary diffusion capacity (CDC). The urinary albumin and beta2-microglobulin concentration were measured by sensitive radioimmunoassays; TER was detemined from the initial disappearance of intravenously injected 125I-labelled human serum albumin; GFR was measured on the forearm by straingauge plethysmography and CDS for 51Cr-EDTA clearance; CFC was measured on the forearm by straingauge plethysmography and CDC, for 51Cr-EDTA was determined in the jyperaemic anterio tibial muscle by the local clearance technique. All the above mentioned variables, except CDC, were significantly increased during poor metabolic regulation, indicating a functional microangiopathy. The mechanisms of these alterations appear to be increased filtration pressure in the microcirculation and/or increased porosity of the microvasculature. The findings of increased microvascular albumin passage are compatible with the hypothesis that the organic - histologicallly demonstrated - diabetic microangiopathy is a long-term effect of periods of increased extravasation of plasma proteins, with subsequent protein deposition in the microvascular wall, i.e. the concept to plasmatic vasculosis.", "contents": "The effect of metabolic regulation on microvascular permeability to small and large molecules in short-term juvenile diabetics. The microvascular permeability to small and large molecules was studied during good and poor metabolic regulation in ten short duration juvenile diabetics. The following variables were measured; daily urinary albumin and beta2-microglobulin-excretion rates, whole body transcapillary escape rate of albumin (TER), glomerular filtration rate (GFR), capillary filtration coefficient (CFC), and capillary diffusion capacity (CDC). The urinary albumin and beta2-microglobulin concentration were measured by sensitive radioimmunoassays; TER was detemined from the initial disappearance of intravenously injected 125I-labelled human serum albumin; GFR was measured on the forearm by straingauge plethysmography and CDS for 51Cr-EDTA clearance; CFC was measured on the forearm by straingauge plethysmography and CDC, for 51Cr-EDTA was determined in the jyperaemic anterio tibial muscle by the local clearance technique. All the above mentioned variables, except CDC, were significantly increased during poor metabolic regulation, indicating a functional microangiopathy. The mechanisms of these alterations appear to be increased filtration pressure in the microcirculation and/or increased porosity of the microvasculature. The findings of increased microvascular albumin passage are compatible with the hypothesis that the organic - histologicallly demonstrated - diabetic microangiopathy is a long-term effect of periods of increased extravasation of plasma proteins, with subsequent protein deposition in the microvascular wall, i.e. the concept to plasmatic vasculosis."} {"id": "PMID:1269851", "title": "Experimental study on the effect of large-dose intratumoral OK-432 administration in mice.", "content": "This experimental study was undertaken to evaluate the effectiveness of a large-dose intratumoral administration of OK-432, which has already been found to be effective when combined with Mitomycin-C, 5-fluorouracil, and cytosine arabinoside, and/or small-dose of OK-432 in clinical use. Large-dose of OK-432 was administered intratumorally 15 days after the subcutaneous inoculation of 2.5 X 10(6) Ehrlich carcinoma cells. At the same time, 2.5 X 10(6) tumor cells were re-challenged intraperitoneally. A combined treatment with a small-dose of OK-432 and Mitomycin-C, cyclophosphamide, or 5-fluorouracil was also made. As a large-dose of OK-432, three-dose regimen of 1,000, 500, and 100 KE/kg was tested. As a small-dose of OK-432, 4 consecutive daily intramuscular injection of 50 KE/kg was examined. From the results obtained the initial intratumoral administration of a large-dose of OK=432 was found to be beneficial for the following combined treatment with a small-dose of OK-432 and Mitomycin-C or cyclophosphamide. The change of phytohemagglutinin (PHA) responsiveness of spleen cells after intratumoral injection of a large-dose of OK-432 was investigated in mice. These results indicated a decrease of PHA responsiveness of spleen cells according to the tumor growth. The intratumoral large-dose administration of OK-432 suggested inhibition of the decrease in PHA responsiveness. The most effective and suitable dose in this experiment was found to be 500 KE/kg in the three-dose regimen.", "contents": "Experimental study on the effect of large-dose intratumoral OK-432 administration in mice. This experimental study was undertaken to evaluate the effectiveness of a large-dose intratumoral administration of OK-432, which has already been found to be effective when combined with Mitomycin-C, 5-fluorouracil, and cytosine arabinoside, and/or small-dose of OK-432 in clinical use. Large-dose of OK-432 was administered intratumorally 15 days after the subcutaneous inoculation of 2.5 X 10(6) Ehrlich carcinoma cells. At the same time, 2.5 X 10(6) tumor cells were re-challenged intraperitoneally. A combined treatment with a small-dose of OK-432 and Mitomycin-C, cyclophosphamide, or 5-fluorouracil was also made. As a large-dose of OK-432, three-dose regimen of 1,000, 500, and 100 KE/kg was tested. As a small-dose of OK-432, 4 consecutive daily intramuscular injection of 50 KE/kg was examined. From the results obtained the initial intratumoral administration of a large-dose of OK=432 was found to be beneficial for the following combined treatment with a small-dose of OK-432 and Mitomycin-C or cyclophosphamide. The change of phytohemagglutinin (PHA) responsiveness of spleen cells after intratumoral injection of a large-dose of OK-432 was investigated in mice. These results indicated a decrease of PHA responsiveness of spleen cells according to the tumor growth. The intratumoral large-dose administration of OK-432 suggested inhibition of the decrease in PHA responsiveness. The most effective and suitable dose in this experiment was found to be 500 KE/kg in the three-dose regimen."} {"id": "PMID:1269852", "title": "Induction of tumors in female Donryu rats by a single administration of 1-propyl-1-nitrosourea.", "content": "Three groups of female Donryu rats were given a single gastric intubation of 800, 400, or 200 mg/kg body weight of 1-propyl-1-nitrosourea and one group of female Donryu rats was given a single subcutaneous injection of 1-propyl-1-nitrosourea. The incidence of tumors was highest for mammary tumors and leukemia, and next for tumors of the ovary, thyroid, and adrenal glands, and in the digestive tract in rats given the chemical by oral administration. There were also scattered tumors in various other organs. Mammary and subcutaneous tumors were found in some rats given a subcutaneous injection of 1-propyl-1-nitrosourea.", "contents": "Induction of tumors in female Donryu rats by a single administration of 1-propyl-1-nitrosourea. Three groups of female Donryu rats were given a single gastric intubation of 800, 400, or 200 mg/kg body weight of 1-propyl-1-nitrosourea and one group of female Donryu rats was given a single subcutaneous injection of 1-propyl-1-nitrosourea. The incidence of tumors was highest for mammary tumors and leukemia, and next for tumors of the ovary, thyroid, and adrenal glands, and in the digestive tract in rats given the chemical by oral administration. There were also scattered tumors in various other organs. Mammary and subcutaneous tumors were found in some rats given a subcutaneous injection of 1-propyl-1-nitrosourea."} {"id": "PMID:1269853", "title": "Carcinogenic activity of coltsfoot, Tussilago farfara l.", "content": "The carcinogenicity of young, pre-blooming flowers of coltsfoot, Tussilago farfara L., which is a herb of the tribe Senecioneae, family Compositae, and widely used as a herbal remedy, was studied in inbred strain ACI rats. Rats were divided into 4 groups: Group I received 32% coltsfoot diet for 4 days, and subsequently 16% diet until the termination of experiment. Groups II and III respectively received 8% and 4% coltsfoot diet for 600 days. Group IV was fed a normal diet as a control group. The experiments were terminated 600 days after the start of administration of coltsfoot diet. All the rats in Group I survived beyond 380 days after the start of feeding and 8 out of 12 rats developed hemangioendothelial sarcoma in the liver, whereas only one out of 10 rats developed the tumor in Group II, and no tumors were observed in Group III. Chemical studies on the dried, young flowers used in this experiment suggested that the carcinogenicity of coltsfoot is most probably due to senkirkine, a hepatotoxic pyrrolizidine alkaloid.", "contents": "Carcinogenic activity of coltsfoot, Tussilago farfara l. The carcinogenicity of young, pre-blooming flowers of coltsfoot, Tussilago farfara L., which is a herb of the tribe Senecioneae, family Compositae, and widely used as a herbal remedy, was studied in inbred strain ACI rats. Rats were divided into 4 groups: Group I received 32% coltsfoot diet for 4 days, and subsequently 16% diet until the termination of experiment. Groups II and III respectively received 8% and 4% coltsfoot diet for 600 days. Group IV was fed a normal diet as a control group. The experiments were terminated 600 days after the start of administration of coltsfoot diet. All the rats in Group I survived beyond 380 days after the start of feeding and 8 out of 12 rats developed hemangioendothelial sarcoma in the liver, whereas only one out of 10 rats developed the tumor in Group II, and no tumors were observed in Group III. Chemical studies on the dried, young flowers used in this experiment suggested that the carcinogenicity of coltsfoot is most probably due to senkirkine, a hepatotoxic pyrrolizidine alkaloid."} {"id": "PMID:1269855", "title": "Transplantable sarcomas induced by 3-methylcholanthrene in inbred guinea pigs of JY-1 and Hartley/F strains.", "content": "Inbred strains of guinea pigs, JY-1 and Hartley/F, established in this Institute, were injected subcutaneously with 3-methylcholanthrene. During 1972 to 1974, 15 solid tumors (7 fibrosarcomas, 6 liposarcomas, and 2 atheroma-like tumors) have been induced in 12 animals out of 30 employed. Among the 15 tumors, 1 fibrosarcoma induced in JY-1 and 2 liposarcomas and 1 fibrosarcoma induced in Hartley/F were transplantable and established as the syngeneic lines named J4, H10, H12, and H9A, respectively. In addition, a transplant of J4 into the Hartley/F strain animal was established as an allogeneic subline and named JH4. Pathological and biological characteristics of these tumors are described and differences between these tumors and line 10 hepatoma, established by Rapp et al. in strain-2 guinea pig, are discussed.", "contents": "Transplantable sarcomas induced by 3-methylcholanthrene in inbred guinea pigs of JY-1 and Hartley/F strains. Inbred strains of guinea pigs, JY-1 and Hartley/F, established in this Institute, were injected subcutaneously with 3-methylcholanthrene. During 1972 to 1974, 15 solid tumors (7 fibrosarcomas, 6 liposarcomas, and 2 atheroma-like tumors) have been induced in 12 animals out of 30 employed. Among the 15 tumors, 1 fibrosarcoma induced in JY-1 and 2 liposarcomas and 1 fibrosarcoma induced in Hartley/F were transplantable and established as the syngeneic lines named J4, H10, H12, and H9A, respectively. In addition, a transplant of J4 into the Hartley/F strain animal was established as an allogeneic subline and named JH4. Pathological and biological characteristics of these tumors are described and differences between these tumors and line 10 hepatoma, established by Rapp et al. in strain-2 guinea pig, are discussed."} {"id": "PMID:1269856", "title": "Large bowel carcinoma in strain-2 guinea pigs by intrarectal instillation of N-methyl-N'-nitro-n-nitrosoguanidine.", "content": "Intrarectal instillation of 0.5 ml of a 0.125% solution of N-methyl-N'-nitro-N-nitrosoguanidine twice weekly for 53 weeks to female inbred strain-2 guinea pigs induced multiple large bowel adenocarcinomas in 13 of 15 animals in 52 to 85 weeks. The lesions were plaque-shaped in small tumors and infiltrative or constrictive in large advanced tumors. The neoplasms showed histological features in varied grades of differentiation and invasiveness similar to those of human cases. These findings distinquished them from large bowel cancers chemically induced in rats and mice.", "contents": "Large bowel carcinoma in strain-2 guinea pigs by intrarectal instillation of N-methyl-N'-nitro-n-nitrosoguanidine. Intrarectal instillation of 0.5 ml of a 0.125% solution of N-methyl-N'-nitro-N-nitrosoguanidine twice weekly for 53 weeks to female inbred strain-2 guinea pigs induced multiple large bowel adenocarcinomas in 13 of 15 animals in 52 to 85 weeks. The lesions were plaque-shaped in small tumors and infiltrative or constrictive in large advanced tumors. The neoplasms showed histological features in varied grades of differentiation and invasiveness similar to those of human cases. These findings distinquished them from large bowel cancers chemically induced in rats and mice."} {"id": "PMID:1269857", "title": "Effect of fundic ulcers induced by iodoacetamide on development of gastric tumors in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine.", "content": "The effect of ulcers induced by iodoacetamine on the development of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine was studied in male Wistar rats. The ulcerative lesions induced by iodoacetamide were confined symmetrically to the fundic region along the limiting ridge in the stomach and the pyloric region was unaffected. Animals treated with iodoacetamide and N-methyl-N'-nitro-N-nitrosoguanidine produced a high incidence of tumors including adenocarcinoma in the fundic region. The incidence of tumors in the pyloric region in the control group was 80% but there were no tumors in the fundic region. The tumors in the fundic region were most frequently found in the same areas that ulcers had previously been induced. These findings suggest that ulceration and regeneration of the mucosa are important factors in gastric carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine.", "contents": "Effect of fundic ulcers induced by iodoacetamide on development of gastric tumors in rats treated with N-methyl-N'-nitro-N-nitrosoguanidine. The effect of ulcers induced by iodoacetamine on the development of gastric tumors by N-methyl-N'-nitro-N-nitrosoguanidine was studied in male Wistar rats. The ulcerative lesions induced by iodoacetamide were confined symmetrically to the fundic region along the limiting ridge in the stomach and the pyloric region was unaffected. Animals treated with iodoacetamide and N-methyl-N'-nitro-N-nitrosoguanidine produced a high incidence of tumors including adenocarcinoma in the fundic region. The incidence of tumors in the pyloric region in the control group was 80% but there were no tumors in the fundic region. The tumors in the fundic region were most frequently found in the same areas that ulcers had previously been induced. These findings suggest that ulceration and regeneration of the mucosa are important factors in gastric carcinogenesis induced in rats by N-methyl-N'-nitro-N-nitrosoguanidine."} {"id": "PMID:1269858", "title": "Analysis of incipient growth of Yoshida sarcoma in vivo after transplantation of a small number of tumor cells.", "content": "Incipient growth of Yoshida sarcoma in ascitic and solid forms was analyzed after transplantation of a small number of tumor cells varying from 1 to 10(6). Growth curves of the ascites tumors revealed that the duration of the incipient growth was much longer than the length of subsequent advanced stage and that the ascites tumor during its incipient stage appeared to grow exponentially and most rapidly in the entire course of the tumor development. Growth rate analyses of the ascites and solid tumors showed that, during their incipient stage, the population doubling time prolonged gradually as the inoculum size increased. This phenomenon was thought to suggest probable cell death on account of the transplantation procedure.", "contents": "Analysis of incipient growth of Yoshida sarcoma in vivo after transplantation of a small number of tumor cells. Incipient growth of Yoshida sarcoma in ascitic and solid forms was analyzed after transplantation of a small number of tumor cells varying from 1 to 10(6). Growth curves of the ascites tumors revealed that the duration of the incipient growth was much longer than the length of subsequent advanced stage and that the ascites tumor during its incipient stage appeared to grow exponentially and most rapidly in the entire course of the tumor development. Growth rate analyses of the ascites and solid tumors showed that, during their incipient stage, the population doubling time prolonged gradually as the inoculum size increased. This phenomenon was thought to suggest probable cell death on account of the transplantation procedure."} {"id": "PMID:1269859", "title": "Histological classification of urinary bladder cancers in rats induced by N-butyl-n-(4-hydroxybutyl)nitrosamine.", "content": "Histological types and grades of 613 urinary bladder cancers induced in rats by N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) were analyzed. Most of them (95.1%) were transitional cell carcinomas, the remainder being squamous cell carcinomas (3.3%), undifferentiated carcinomas (2.5%), and carcinosarcomas (0.3%). Among the transitional cell carcinomas, 23.3% were Grade I anaplasia, 55.2% Grade II, and 21.5% Grade III. Among the squamous cell carcinomas, 20% each were Grade I and II, and 60% Grade III. Most of the undifferentiated carcinomas were Grade III. Some of the cases of transitional cell carcinoma had areas of squamous metaplasia and/or glandular metaplasia, and the incidence of metaplasia increased with the grade of anaplasia. Approximately 36% of the cases of transitional cell carcinoma were of the invasive type. Invasive types were twice as numerous among cases of squamous cell carcinoma as among those of transitional cell carcinoma and all of undifferentiated carcinomas were invasive. The incidence of invasive type was closely related to the grade of anaplasia. These results show that the morphological characteristics of urinary bladder carcinomas induced by BBN in rats are similar to those seen clinically in humans.", "contents": "Histological classification of urinary bladder cancers in rats induced by N-butyl-n-(4-hydroxybutyl)nitrosamine. Histological types and grades of 613 urinary bladder cancers induced in rats by N-butyl-N-(4-hydroxybutyl) nitrosamine(BBN) were analyzed. Most of them (95.1%) were transitional cell carcinomas, the remainder being squamous cell carcinomas (3.3%), undifferentiated carcinomas (2.5%), and carcinosarcomas (0.3%). Among the transitional cell carcinomas, 23.3% were Grade I anaplasia, 55.2% Grade II, and 21.5% Grade III. Among the squamous cell carcinomas, 20% each were Grade I and II, and 60% Grade III. Most of the undifferentiated carcinomas were Grade III. Some of the cases of transitional cell carcinoma had areas of squamous metaplasia and/or glandular metaplasia, and the incidence of metaplasia increased with the grade of anaplasia. Approximately 36% of the cases of transitional cell carcinoma were of the invasive type. Invasive types were twice as numerous among cases of squamous cell carcinoma as among those of transitional cell carcinoma and all of undifferentiated carcinomas were invasive. The incidence of invasive type was closely related to the grade of anaplasia. These results show that the morphological characteristics of urinary bladder carcinomas induced by BBN in rats are similar to those seen clinically in humans."} {"id": "PMID:1269860", "title": "The effect of betazole on serum group I pepsinogen levels: studies in symptomatic patients with and without recurrent ulcer after vagotomy and gastric resection or drainage.", "content": "Serum group I pepsinogen (PG I) levels have been determined before and at intervals after the administration of betazole hydrochloride (Histalog) in 50 symptomatic postoperative patients, 20 with and 30 without recurrent ulcer, after either a vagotomy and gastric resection or a drainage procedure. In patients with recurrent ulcer, mean serum PG I levels increased after betazole and reached a maximum of 116.5 +/- 2.2% (SE) of basal at 2 hr; range 98.9 to 135.7%. In contrast, mean serum PG I levels decreased in patients without recurrent ulcer and reached a nadir of 75.0 +/- 4.3% of basal at 2 hr; range 46.9 to 142.4%. All 20 patients with recurrent ulcer and 5 patients without recurrence had a 2-hr serum PG I level of more than 98% of basal, while each of the remaining 25 patients without recurrent ulcer had a 2-hr level of less than 92% of basal. A 2-hr serum PG I level of more than 98% of basal was also correlated with a vagotomy and drainage, a peak acid output of more than 11 mEq per hr, and a positive insulin test, while a level of less than 92% of basal was correlated with a vagotomy and gastric resection, a peak acid output of less than 11 mEq per hr, and a negative insulin test. In addition, basal serum PG I and serum gastrin levels were significantly higher (P less than 0.001) in patients with the former type of PG I response than in those with the latter type of response. The cause of each type of response is not certain, but the data suggest that one of the determinants may be the completeness of vagotomy.", "contents": "The effect of betazole on serum group I pepsinogen levels: studies in symptomatic patients with and without recurrent ulcer after vagotomy and gastric resection or drainage. Serum group I pepsinogen (PG I) levels have been determined before and at intervals after the administration of betazole hydrochloride (Histalog) in 50 symptomatic postoperative patients, 20 with and 30 without recurrent ulcer, after either a vagotomy and gastric resection or a drainage procedure. In patients with recurrent ulcer, mean serum PG I levels increased after betazole and reached a maximum of 116.5 +/- 2.2% (SE) of basal at 2 hr; range 98.9 to 135.7%. In contrast, mean serum PG I levels decreased in patients without recurrent ulcer and reached a nadir of 75.0 +/- 4.3% of basal at 2 hr; range 46.9 to 142.4%. All 20 patients with recurrent ulcer and 5 patients without recurrence had a 2-hr serum PG I level of more than 98% of basal, while each of the remaining 25 patients without recurrent ulcer had a 2-hr level of less than 92% of basal. A 2-hr serum PG I level of more than 98% of basal was also correlated with a vagotomy and drainage, a peak acid output of more than 11 mEq per hr, and a positive insulin test, while a level of less than 92% of basal was correlated with a vagotomy and gastric resection, a peak acid output of less than 11 mEq per hr, and a negative insulin test. In addition, basal serum PG I and serum gastrin levels were significantly higher (P less than 0.001) in patients with the former type of PG I response than in those with the latter type of response. The cause of each type of response is not certain, but the data suggest that one of the determinants may be the completeness of vagotomy."} {"id": "PMID:1269861", "title": "Serum lysozyme in inflammatory bowel disease.", "content": "Serum lysozyme (muramidase) concentrations were measured in three groups of patients: control, ulcerative colitis and proctitis, and Crohn's disease. The mean +/-SD for each group was: control, 7 +/- 2; ulcerative colitis and proctitis, 7 +/- 2; and Crohn's disease, 10 +/- 4. Although a significant difference was seen between values in patients with Crohn's disease and values observed in those with ulcerative colitis or control patients, an important overlap was found between these groups. Further studies are necessary to explain the disparate results between this study and previous reports.", "contents": "Serum lysozyme in inflammatory bowel disease. Serum lysozyme (muramidase) concentrations were measured in three groups of patients: control, ulcerative colitis and proctitis, and Crohn's disease. The mean +/-SD for each group was: control, 7 +/- 2; ulcerative colitis and proctitis, 7 +/- 2; and Crohn's disease, 10 +/- 4. Although a significant difference was seen between values in patients with Crohn's disease and values observed in those with ulcerative colitis or control patients, an important overlap was found between these groups. Further studies are necessary to explain the disparate results between this study and previous reports."} {"id": "PMID:1269862", "title": "Thrombocytosis in patients with celiac sprue.", "content": "In 57% of the patients (12 of 25) seen with celiac sprue, as shown by clinical course and small bowel biopsy, peripheral blood thrombocytosis was present (range: 350,000 to 815,000 platelets per mm(3); mean: 546,000 +/- 44,060 SE). After clinical and histological remission, the platelet counts in these patients fell significantly (range: 188,000 to 300,0000 platelets per mm(3); mean 252,750 +/- 13,211 SE). There was no correlation between thrombocytosis and serum iron, folate, or vitamin B12 levels. Celiac sprue joins inflammatory bowel disease among gastrointestinal disorders as a consideration in the differential diagnosis of thrombocytosis. In these patients, thrombocytosis reflected active disease and was not present during remission. Evaluation of peripheral blood platelets may be useful in the assessment of patients with celiac sprue.", "contents": "Thrombocytosis in patients with celiac sprue. In 57% of the patients (12 of 25) seen with celiac sprue, as shown by clinical course and small bowel biopsy, peripheral blood thrombocytosis was present (range: 350,000 to 815,000 platelets per mm(3); mean: 546,000 +/- 44,060 SE). After clinical and histological remission, the platelet counts in these patients fell significantly (range: 188,000 to 300,0000 platelets per mm(3); mean 252,750 +/- 13,211 SE). There was no correlation between thrombocytosis and serum iron, folate, or vitamin B12 levels. Celiac sprue joins inflammatory bowel disease among gastrointestinal disorders as a consideration in the differential diagnosis of thrombocytosis. In these patients, thrombocytosis reflected active disease and was not present during remission. Evaluation of peripheral blood platelets may be useful in the assessment of patients with celiac sprue."} {"id": "PMID:1269863", "title": "Tissue plasminogen activator in the pathogenesis of protein-losing gastroenteropathy.", "content": "Tissue fibrinolytic activity, mainly due to activator of tissue plasminogen was increased in the biopsied gastric mucosa of patients with protein-losing gastropathy. Antiplasmin therapy with trans-AMCHA (trans-4-aminomethyl cyclohexane carboxylic acid) was dramatically effective, except in the case of a patient with intestinal lymphangiectasia. These findings suggest that increased fibrinolysis in the gastrointestinal mucosa may play an important role in enhancing mucosal permeability to plasma proteins.", "contents": "Tissue plasminogen activator in the pathogenesis of protein-losing gastroenteropathy. Tissue fibrinolytic activity, mainly due to activator of tissue plasminogen was increased in the biopsied gastric mucosa of patients with protein-losing gastropathy. Antiplasmin therapy with trans-AMCHA (trans-4-aminomethyl cyclohexane carboxylic acid) was dramatically effective, except in the case of a patient with intestinal lymphangiectasia. These findings suggest that increased fibrinolysis in the gastrointestinal mucosa may play an important role in enhancing mucosal permeability to plasma proteins."} {"id": "PMID:1269864", "title": "What the gastroenterologist does all day. A survey of a state society's practice.", "content": "Members of a state society of gastroenterologist collected information about their pattern of practice. Twenty-two of the 41 members voluntarily kept a list of 25 sequential new patients seen during the spring of 1973. Five hundred and fory-nine diagnoses were accumulated; 369 (67%) of these diagnoses were gastroenterological. The five most common gastroenterological diagnoses were: functional disorder, duodenal ulcer, hiatus hernia, biliary tract disease, and esophagitis. The five most common over-all diagnostic areas were: functional disorder, cardiovascular disease, \"other\" nongastroenterological diagnoses (including obesity), duodenal ulcer, and endocrine malfunction. Geographically dispersed gastroenterologists in Virginia make more than one-half of their primary diagnoses in the area of their subspecialty interest. The primary gastroenterological problems seen are \"upper gut\" lesions and biliary tract disease. These observations may be of value in planning education, training, or research activities, especially if verified by a broader sample of gastroenterological practitioners.", "contents": "What the gastroenterologist does all day. A survey of a state society's practice. Members of a state society of gastroenterologist collected information about their pattern of practice. Twenty-two of the 41 members voluntarily kept a list of 25 sequential new patients seen during the spring of 1973. Five hundred and fory-nine diagnoses were accumulated; 369 (67%) of these diagnoses were gastroenterological. The five most common gastroenterological diagnoses were: functional disorder, duodenal ulcer, hiatus hernia, biliary tract disease, and esophagitis. The five most common over-all diagnostic areas were: functional disorder, cardiovascular disease, \"other\" nongastroenterological diagnoses (including obesity), duodenal ulcer, and endocrine malfunction. Geographically dispersed gastroenterologists in Virginia make more than one-half of their primary diagnoses in the area of their subspecialty interest. The primary gastroenterological problems seen are \"upper gut\" lesions and biliary tract disease. These observations may be of value in planning education, training, or research activities, especially if verified by a broader sample of gastroenterological practitioners."} {"id": "PMID:1269865", "title": "Quantitative measurement of lactose absorption.", "content": "The quantity of lactose not absorbed by 4 normal and 6 lactase-deficient subjects was determined by three indirect methods which involved: (1) measurement of pulmonary hydrogen (H2) excretion, (2) pulmonary (14)CO2 excretion, and (3) stool (14)C excretion, after ingestion of 12.5 g of 1-(14)C-lactose and 4 g of polyethylene glycol (PEG). Results were compared with absorption determined directly from the (14)C:PEG ratio of multiple terminal ileal aspirates. The fraction of lactose not absorbed determined by ileal aspiration ranged from 0 to 8% in normals and 42 to 75% in mild-intolerant subjects. Whereas all three indirect methods were useful in qualitatively separating normal from deficient subjects, the quantity of lactose absorbed as determined by H2 excretion correlated most closely with ileal measurements (r = 0.94). Pulmonary (14)CO2 excretion for 24 hr after (14)C-lactose ingestion did not distinguish normal (17 +/- 4% (SEM) of ingested (14)C per 24 hr) from lactase-deficient subjects (21.1 +/- 3%). Likewise, stool (14)C:PEG ratios grossly underestimated malabsorption with less than one-quarter of the nonabsorbed (14)C appearing in the stool. This study suggests that individual differences in susceptibility to diarrhea after milk ingestion by lactase-deficient subjects may be due to differences in the quantity of lactose not absorbed and/or differences in the rate of bacterial metabolism of lactose in the colon. Analysis of ileal fluid collected during passage of the lactose meal indicated that about two-thirds of the osmotic load delivered to the colon consists of endogenous electrolytes. Thus the water load delivered to the colon is about 3 times that calculated to be osmotically held by the nonabsorbed sugar.", "contents": "Quantitative measurement of lactose absorption. The quantity of lactose not absorbed by 4 normal and 6 lactase-deficient subjects was determined by three indirect methods which involved: (1) measurement of pulmonary hydrogen (H2) excretion, (2) pulmonary (14)CO2 excretion, and (3) stool (14)C excretion, after ingestion of 12.5 g of 1-(14)C-lactose and 4 g of polyethylene glycol (PEG). Results were compared with absorption determined directly from the (14)C:PEG ratio of multiple terminal ileal aspirates. The fraction of lactose not absorbed determined by ileal aspiration ranged from 0 to 8% in normals and 42 to 75% in mild-intolerant subjects. Whereas all three indirect methods were useful in qualitatively separating normal from deficient subjects, the quantity of lactose absorbed as determined by H2 excretion correlated most closely with ileal measurements (r = 0.94). Pulmonary (14)CO2 excretion for 24 hr after (14)C-lactose ingestion did not distinguish normal (17 +/- 4% (SEM) of ingested (14)C per 24 hr) from lactase-deficient subjects (21.1 +/- 3%). Likewise, stool (14)C:PEG ratios grossly underestimated malabsorption with less than one-quarter of the nonabsorbed (14)C appearing in the stool. This study suggests that individual differences in susceptibility to diarrhea after milk ingestion by lactase-deficient subjects may be due to differences in the quantity of lactose not absorbed and/or differences in the rate of bacterial metabolism of lactose in the colon. Analysis of ileal fluid collected during passage of the lactose meal indicated that about two-thirds of the osmotic load delivered to the colon consists of endogenous electrolytes. Thus the water load delivered to the colon is about 3 times that calculated to be osmotically held by the nonabsorbed sugar."} {"id": "PMID:1269866", "title": "Histamine receptors in esophageal smooth muscle of the opossum.", "content": "Esophageal smooth muscle was examined for histamine receptors. The effects of histamine, the histamine analogs 4-methylhistamine (4-MH) and 2-(2-pyridyl) ethylamine (PEA), the histamine receptor antagonists mepyramine and metiamide, and the histamine-releasing substance compound 48/80, on lower esophageal sphincter (LES) and esophageal body (EB) smooth muscle of the opossum were studied in a superfused tissue bath. Histamine, PEA, an H1 receptor agonist, and compound 48/80 caused a dose-related increase in LES basal tension and in EB off response amplitude, the threshold for histamine being 6.7 X 10(-8) M and that for PEA being 6.7 X 10(-7) M. In the presence of mepyramine, and H1 receptor antagonist, the effects of histamine and compound 48/80 were reversed to inhibition of both LES basal tension and EB off response amplitude, while the effect of PEA was abolished. Metiamide, an H2 receptor antagonist, did not alter responses to histamine, PEA, or compound 48/80. The H2 receptor agonist 4-methylhistamine caused a reduction of LES tension and EB off response amplitude, but caused an increase in those parameters in the presence of metiamide. A combination of mepyramine and metiamide abolished responses to all agonist drugs. The results indicate that LES and EB smooth muscle contain both excitatory H1 and inhibitory H2 receptors for histamine. Endogenous histamine released from storage sites in LES and EB and exogenous histamine both preferentially activate H1 receptors.", "contents": "Histamine receptors in esophageal smooth muscle of the opossum. Esophageal smooth muscle was examined for histamine receptors. The effects of histamine, the histamine analogs 4-methylhistamine (4-MH) and 2-(2-pyridyl) ethylamine (PEA), the histamine receptor antagonists mepyramine and metiamide, and the histamine-releasing substance compound 48/80, on lower esophageal sphincter (LES) and esophageal body (EB) smooth muscle of the opossum were studied in a superfused tissue bath. Histamine, PEA, an H1 receptor agonist, and compound 48/80 caused a dose-related increase in LES basal tension and in EB off response amplitude, the threshold for histamine being 6.7 X 10(-8) M and that for PEA being 6.7 X 10(-7) M. In the presence of mepyramine, and H1 receptor antagonist, the effects of histamine and compound 48/80 were reversed to inhibition of both LES basal tension and EB off response amplitude, while the effect of PEA was abolished. Metiamide, an H2 receptor antagonist, did not alter responses to histamine, PEA, or compound 48/80. The H2 receptor agonist 4-methylhistamine caused a reduction of LES tension and EB off response amplitude, but caused an increase in those parameters in the presence of metiamide. A combination of mepyramine and metiamide abolished responses to all agonist drugs. The results indicate that LES and EB smooth muscle contain both excitatory H1 and inhibitory H2 receptors for histamine. Endogenous histamine released from storage sites in LES and EB and exogenous histamine both preferentially activate H1 receptors."} {"id": "PMID:1269867", "title": "After vagotomy atropine suppresses gastrin release by food.", "content": "Changes in serum gastrin in response to feeding a meal of beef liver (15 g kg(-1)) were studied in 5 gastric fistula dogs with and without administration of atropine sulfate (0.2 mg kg(-1) intravenously). The studies were repeated after a truncal vagotomy that abolished acid secretion in response to 2-deoxyglucose. Before vagotomy atropine had little effect on the gastrin response to a meal. After vagotomy the gastrin response to feeding was greatly enhanced, but now atropine depressed the gastrin response at all times after the meal. It is concluded that vagotomy enhances the serum gastrin response to feeding and that atropine counteracts this enhancement.", "contents": "After vagotomy atropine suppresses gastrin release by food. Changes in serum gastrin in response to feeding a meal of beef liver (15 g kg(-1)) were studied in 5 gastric fistula dogs with and without administration of atropine sulfate (0.2 mg kg(-1) intravenously). The studies were repeated after a truncal vagotomy that abolished acid secretion in response to 2-deoxyglucose. Before vagotomy atropine had little effect on the gastrin response to a meal. After vagotomy the gastrin response to feeding was greatly enhanced, but now atropine depressed the gastrin response at all times after the meal. It is concluded that vagotomy enhances the serum gastrin response to feeding and that atropine counteracts this enhancement."} {"id": "PMID:1269868", "title": "Transmissible gastroenteritis. Mucosal ion transport in acute viral enteritis.", "content": "Ion transport in the jejunal mucosa of 14-to 16-day-old piglets with severe diarrhea 40 hr after infection with transmissible gastroenteritis (TGE) virus was studied. In infected pigs Na+ transport failed to respond normally to glucose when studied either in Ussing short-circuited chambers or in suspensions of enterocytes isolated selectively from jejunal villi. Theophylline, 10mM, added to the chambers produced the same brisk electrical responses and increments in net Cl- secretion in tissue from both infected and control groups. A defect in glucose-stimulated Na+ absorption in the acute stage of a viral enteritis has been identified which probably contributes to the impaired lumen-to-extracellular fluid flux of Na+ found previously in the jejunum of intact TGE-infected pigs. The mechanisms causing diarrhea in this invasive viral enteritis differ from those causing toxigenic diarrhea.", "contents": "Transmissible gastroenteritis. Mucosal ion transport in acute viral enteritis. Ion transport in the jejunal mucosa of 14-to 16-day-old piglets with severe diarrhea 40 hr after infection with transmissible gastroenteritis (TGE) virus was studied. In infected pigs Na+ transport failed to respond normally to glucose when studied either in Ussing short-circuited chambers or in suspensions of enterocytes isolated selectively from jejunal villi. Theophylline, 10mM, added to the chambers produced the same brisk electrical responses and increments in net Cl- secretion in tissue from both infected and control groups. A defect in glucose-stimulated Na+ absorption in the acute stage of a viral enteritis has been identified which probably contributes to the impaired lumen-to-extracellular fluid flux of Na+ found previously in the jejunum of intact TGE-infected pigs. The mechanisms causing diarrhea in this invasive viral enteritis differ from those causing toxigenic diarrhea."} {"id": "PMID:1269869", "title": "Effect of bile salts and fatty acids on the colonic absorption of oxalate.", "content": "These studies were designed to evaluate the effect of bile salts and fatty acids on colonic oxalate absorption. Five millimolar deoxycholate significantly increased oxalate absorption from 34.2 +/- 9.4 nmoles per min per g dry weight to 330.4 +/- 47.3 (P less than 0.001) and changed water absorption to water secretion. Deoxycholate also increased the absorption of urea, decreased the electrical potential difference, and increased colonic clearance of oxalate, observations which are consistent with an increase in colonic mucosal permeability. In contrast, taurocholate did not increase oxalate absorption. Ricinoleic acid also significantly increased the absorption. These results suggest that bile salts and fatty acids increase colonic absorption of oxalate. Oleic acid had similar effects on oxalate absorption but was less effective than ricinoleic acid. Octanoic acid, a medium chain fatty acid, did not alter oxalate absorption of oxalate by a nonspecific alteration of mucosal permeability. These observations may further explain many of the clinical phenomena associated with enteric hyperoxaluria.", "contents": "Effect of bile salts and fatty acids on the colonic absorption of oxalate. These studies were designed to evaluate the effect of bile salts and fatty acids on colonic oxalate absorption. Five millimolar deoxycholate significantly increased oxalate absorption from 34.2 +/- 9.4 nmoles per min per g dry weight to 330.4 +/- 47.3 (P less than 0.001) and changed water absorption to water secretion. Deoxycholate also increased the absorption of urea, decreased the electrical potential difference, and increased colonic clearance of oxalate, observations which are consistent with an increase in colonic mucosal permeability. In contrast, taurocholate did not increase oxalate absorption. Ricinoleic acid also significantly increased the absorption. These results suggest that bile salts and fatty acids increase colonic absorption of oxalate. Oleic acid had similar effects on oxalate absorption but was less effective than ricinoleic acid. Octanoic acid, a medium chain fatty acid, did not alter oxalate absorption of oxalate by a nonspecific alteration of mucosal permeability. These observations may further explain many of the clinical phenomena associated with enteric hyperoxaluria."} {"id": "PMID:1269870", "title": "Augmentation of ethanol absorption by mono- and disaccharides.", "content": "Assessment of the influence of nutritional substrates on the disposition of ingested ethanol from the blood requires, first, an understanding of the influence that these may exert upon ethanol absorption from the gastrointestinal tract. In this report, the effects of various carbohydrates on the intestinal absorption of ethanol were studied. When carbohydrates (50 mM) were perfused simultaneously with ethanol (50 mM) in vivo in the rat small bowel, ethanol absorption increased up to 34% (P less than 0.005) above controls receiving ethanol alone. Of the monosaccharides, fructose, 3-O-methylglucose, glucose, or galactose added to an ethanol perfusate, only glucose or galactose increased ethanol absorption over control animals receiving ethanol alone. Of the disaccharides tested, sucrose and maltose, but not lactose, enhanced ethanol absorption. Addition of varying concentrations of maltose to an ethanol perfusate augmented ethanol absorption in a direct proportion to the quantity of glucose absorbed, rather than to the quantity of maltose hydrolyzed. Augmentation of ethanol absorption by carbohydrates appears to be dependent upon sugar-active transport. Ethanol, dissolved in intraluminal water, may cross the mucosa in water absorbed during sugar-active transport. This quantity of ethanol is absorbed in addition to that which normally crosses the mucosa by diffusion down its concentration gradient.", "contents": "Augmentation of ethanol absorption by mono- and disaccharides. Assessment of the influence of nutritional substrates on the disposition of ingested ethanol from the blood requires, first, an understanding of the influence that these may exert upon ethanol absorption from the gastrointestinal tract. In this report, the effects of various carbohydrates on the intestinal absorption of ethanol were studied. When carbohydrates (50 mM) were perfused simultaneously with ethanol (50 mM) in vivo in the rat small bowel, ethanol absorption increased up to 34% (P less than 0.005) above controls receiving ethanol alone. Of the monosaccharides, fructose, 3-O-methylglucose, glucose, or galactose added to an ethanol perfusate, only glucose or galactose increased ethanol absorption over control animals receiving ethanol alone. Of the disaccharides tested, sucrose and maltose, but not lactose, enhanced ethanol absorption. Addition of varying concentrations of maltose to an ethanol perfusate augmented ethanol absorption in a direct proportion to the quantity of glucose absorbed, rather than to the quantity of maltose hydrolyzed. Augmentation of ethanol absorption by carbohydrates appears to be dependent upon sugar-active transport. Ethanol, dissolved in intraluminal water, may cross the mucosa in water absorbed during sugar-active transport. This quantity of ethanol is absorbed in addition to that which normally crosses the mucosa by diffusion down its concentration gradient."} {"id": "PMID:1269871", "title": "Effects of phototherapy on hepatic function in human alcoholic cirrhosis.", "content": "Phototherapy has been used to treat neonatal jaundice, but little assessment has been made of possible beneficial effects on adult liver disease. Effects of phototherapy on bile acid turnover, biliary lipid concentration, liver function tests, and bromosulfophthalein (BSP) kinetics were studied in 8 alcoholic cirrhotics. Phototherapy initially increased biliary specific activity of both primary bile acids and then produced an acceleration of cholic and chenodeoxycholic acid decay curves. Pruritus was relieved in the 3 patients who had this symptom. The proposed mechanism for these changes is mobilization of bile acids from an expanded cutaneous bile acid pool with augmented bile acid excretion. No significant change in serum liver function tests or BSP plasma disappearance curves was seen. Phototherapy causes little improvement in intrinsic liver function, but produces specific changes in bile acid metabolism; these changes may be related to effects of light on a cutaneous bile acid pool.", "contents": "Effects of phototherapy on hepatic function in human alcoholic cirrhosis. Phototherapy has been used to treat neonatal jaundice, but little assessment has been made of possible beneficial effects on adult liver disease. Effects of phototherapy on bile acid turnover, biliary lipid concentration, liver function tests, and bromosulfophthalein (BSP) kinetics were studied in 8 alcoholic cirrhotics. Phototherapy initially increased biliary specific activity of both primary bile acids and then produced an acceleration of cholic and chenodeoxycholic acid decay curves. Pruritus was relieved in the 3 patients who had this symptom. The proposed mechanism for these changes is mobilization of bile acids from an expanded cutaneous bile acid pool with augmented bile acid excretion. No significant change in serum liver function tests or BSP plasma disappearance curves was seen. Phototherapy causes little improvement in intrinsic liver function, but produces specific changes in bile acid metabolism; these changes may be related to effects of light on a cutaneous bile acid pool."} {"id": "PMID:1269872", "title": "Coproporphyrin isomers in Dubin-Johnson syndrome.", "content": "To shed light on the nature of abnormal porphyrin metabolism in Dubin-Johnson syndrome (DJS), coproporphyrin isomer distribution in urine and bile was investigated in carriers and patients with DJS selected from among the families in the cluster area of the syndrome in Japan. Urinary total coproporphyrin content in patients with DJS exceeded that of normal controls (P less than 0.01). However, the increase in urinary excretion of total coproporphyrin was of a much lesser degree compared to a remarkable increase in urinary total coproporphyrin reported for erythropoietic porphyria in which a deficiency of uroporphyrinogen III cosynthetase had been demonstrated. Urinary total coproporphyrin content in carriers was significantly smaller than that of normal controls (P less than 0.05). This paradoxical decrease of urinary total coproporphyrin concentration in DJS carriers was observed in consequence of a decrease in coproporphyrin III excretion without concomitant increase in type I isomer. Administration of griseofulvin, in the dose which had been shown to precipitate attacks of acute porphyria in susceptible subjects, to carriers and patients with DJS did not elicit clinical signs suggestive of porphyria, and urinary total coproporphyrin concentration and the percentage of coproporphyrin I remained unchanged. These results were interpreted to demonstrate an aspect of DJS that was not consistent with the hypothesis that a partial defect in uroporphyrinogen III cosynthetase of the liver might be the cause of DJS. Coproporphyrin in the bile of DJS patients was preponderantly type I.", "contents": "Coproporphyrin isomers in Dubin-Johnson syndrome. To shed light on the nature of abnormal porphyrin metabolism in Dubin-Johnson syndrome (DJS), coproporphyrin isomer distribution in urine and bile was investigated in carriers and patients with DJS selected from among the families in the cluster area of the syndrome in Japan. Urinary total coproporphyrin content in patients with DJS exceeded that of normal controls (P less than 0.01). However, the increase in urinary excretion of total coproporphyrin was of a much lesser degree compared to a remarkable increase in urinary total coproporphyrin reported for erythropoietic porphyria in which a deficiency of uroporphyrinogen III cosynthetase had been demonstrated. Urinary total coproporphyrin content in carriers was significantly smaller than that of normal controls (P less than 0.05). This paradoxical decrease of urinary total coproporphyrin concentration in DJS carriers was observed in consequence of a decrease in coproporphyrin III excretion without concomitant increase in type I isomer. Administration of griseofulvin, in the dose which had been shown to precipitate attacks of acute porphyria in susceptible subjects, to carriers and patients with DJS did not elicit clinical signs suggestive of porphyria, and urinary total coproporphyrin concentration and the percentage of coproporphyrin I remained unchanged. These results were interpreted to demonstrate an aspect of DJS that was not consistent with the hypothesis that a partial defect in uroporphyrinogen III cosynthetase of the liver might be the cause of DJS. Coproporphyrin in the bile of DJS patients was preponderantly type I."} {"id": "PMID:1269873", "title": "Influence of cholic and chenodeoxycholic acid on canalicular bile flow in man.", "content": "Hepatic bile flow was measured and hepatic [(14C]mannitol clearance was calculated during depletion of the bile acid pool and during duodenal administration of cholic or chenodeoxycholic acid in 10 patients 7 to 12 days after operation for uncomplicated gallstone disease. The relationship between [(14)C]mannitol clearance and bile flow was linear, with a regression coefficient which was not significantly different from unity. This finding supported the assumption that mannitol clearance can be used as a measure of canalicular bile flow in man. Linear relationships between bile acid secretion rate and bile flow and bile acid secretion rate and [(14)C]mannitol clearance were found during depletion of the bile acid pool (secretion of cholic, chenodeoxycholic, and deoxycholic acids; relative concentrations, 1.0:1.0:0.5) as well as during cholic acid infusion (73 +/- 3% cholic acid in the secreted hepatic bile) and during chenodeoxycholic acid infusion (88 +/- 2% chenodeoxycholic acid in the secreted hepatic bile). The bile flow dependence on bile acids 0.011 +/- 0.002 ml mumoles(-1)) was not significantly different for \"mixed\" bile acid secretion, mainly cholic acid secretion, or mainly chenodeoxycholic acid secretion. Neither was the ductular bile flow (0.08 +/- 0.03 ml min(-1)) significantly influenced by the various experimental conditions. The canalicular flow--the bile acid-independent (0.17 +/- 0.05 ml min(-1)) and the bile acid-dependent flow--constituted 70 to 85% of the total bile flow. It is concluded that secretion of cholic acid and of chenodeoxycholic acid promote the same bile flow volume per micromole in man.", "contents": "Influence of cholic and chenodeoxycholic acid on canalicular bile flow in man. Hepatic bile flow was measured and hepatic [(14C]mannitol clearance was calculated during depletion of the bile acid pool and during duodenal administration of cholic or chenodeoxycholic acid in 10 patients 7 to 12 days after operation for uncomplicated gallstone disease. The relationship between [(14)C]mannitol clearance and bile flow was linear, with a regression coefficient which was not significantly different from unity. This finding supported the assumption that mannitol clearance can be used as a measure of canalicular bile flow in man. Linear relationships between bile acid secretion rate and bile flow and bile acid secretion rate and [(14)C]mannitol clearance were found during depletion of the bile acid pool (secretion of cholic, chenodeoxycholic, and deoxycholic acids; relative concentrations, 1.0:1.0:0.5) as well as during cholic acid infusion (73 +/- 3% cholic acid in the secreted hepatic bile) and during chenodeoxycholic acid infusion (88 +/- 2% chenodeoxycholic acid in the secreted hepatic bile). The bile flow dependence on bile acids 0.011 +/- 0.002 ml mumoles(-1)) was not significantly different for \"mixed\" bile acid secretion, mainly cholic acid secretion, or mainly chenodeoxycholic acid secretion. Neither was the ductular bile flow (0.08 +/- 0.03 ml min(-1)) significantly influenced by the various experimental conditions. The canalicular flow--the bile acid-independent (0.17 +/- 0.05 ml min(-1)) and the bile acid-dependent flow--constituted 70 to 85% of the total bile flow. It is concluded that secretion of cholic acid and of chenodeoxycholic acid promote the same bile flow volume per micromole in man."} {"id": "PMID:1269874", "title": "Effects of ethinyl estradiol and phenobarbital on bile acid synthesis and biliary bile acid and cholesterol excretion.", "content": "Bile acid synthesis calculated from respiratory (14)CO2 derived from the catabolism of [26 or 27-(14)C]cholesterol to bile acids in rats with intact enterohepatic circulations decreased 50% after 5 days of ethinyl estradiol treatment (5 mg per kg per day). Maximal derepressed bile acid synthesis, measured as biliary bile acid excretion after bile acid pool depletion, was also reduced 50% by ethinyl estradiol treatment. Because ethinyl estradiol did not alter biliary cholesterol excretion, bile contained less bile acid relative to cholesterol. Hepatic bile acid concentration was not increased by ethinyl estradiol treatment. Because the inhibitory effect of ethinyl estradiol on bile acid synthesis required 5 days of treatment it is concluded that bile acid synthesis probably was not reduced by negative feedback repression of 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis, which has a half-life of 2 to 3 hr. During the first 14 hr after bile duct cannulation, before bile acid pool depletion, ethinyl estradiol-treated rats excreted less than one-half as much bile acid and the same amount of cholesterol as controls. The bile acid to cholesterol ratio was therefore decreased. Rats treated simultaneously with phenobarbital and ethinyl estradiol excreted significantly more bile acid than rats treated with ethinyl estradiol alone, but biliary cholesterol excretion was not increased. The proportion of biliary bile acid relative to cholesterol was thereby restored to the control value. In contrast, after 14 hr of bile drainage and depletion of the bile acid pool, rats treated with ethinyl estradiol and those treated with phenobarbital-ethinyl estradiol excreted the same amount of bile acid. Thus, when phenobarbital is administered with ethinyl estradiol, it increases the bile acid pool size and biliary bile acid excretion, but it does not increase bile acid synthesis. The increase in pool size and biliary bile acid excretion might be due to the phenobarbital-induced increase in ileal absorption of bile acids.", "contents": "Effects of ethinyl estradiol and phenobarbital on bile acid synthesis and biliary bile acid and cholesterol excretion. Bile acid synthesis calculated from respiratory (14)CO2 derived from the catabolism of [26 or 27-(14)C]cholesterol to bile acids in rats with intact enterohepatic circulations decreased 50% after 5 days of ethinyl estradiol treatment (5 mg per kg per day). Maximal derepressed bile acid synthesis, measured as biliary bile acid excretion after bile acid pool depletion, was also reduced 50% by ethinyl estradiol treatment. Because ethinyl estradiol did not alter biliary cholesterol excretion, bile contained less bile acid relative to cholesterol. Hepatic bile acid concentration was not increased by ethinyl estradiol treatment. Because the inhibitory effect of ethinyl estradiol on bile acid synthesis required 5 days of treatment it is concluded that bile acid synthesis probably was not reduced by negative feedback repression of 7alpha-hydroxylase, the rate-limiting enzyme in bile acid synthesis, which has a half-life of 2 to 3 hr. During the first 14 hr after bile duct cannulation, before bile acid pool depletion, ethinyl estradiol-treated rats excreted less than one-half as much bile acid and the same amount of cholesterol as controls. The bile acid to cholesterol ratio was therefore decreased. Rats treated simultaneously with phenobarbital and ethinyl estradiol excreted significantly more bile acid than rats treated with ethinyl estradiol alone, but biliary cholesterol excretion was not increased. The proportion of biliary bile acid relative to cholesterol was thereby restored to the control value. In contrast, after 14 hr of bile drainage and depletion of the bile acid pool, rats treated with ethinyl estradiol and those treated with phenobarbital-ethinyl estradiol excreted the same amount of bile acid. Thus, when phenobarbital is administered with ethinyl estradiol, it increases the bile acid pool size and biliary bile acid excretion, but it does not increase bile acid synthesis. The increase in pool size and biliary bile acid excretion might be due to the phenobarbital-induced increase in ileal absorption of bile acids."} {"id": "PMID:1269875", "title": "Quinidine hepatotoxicity. A report of a case and review of the literature.", "content": "A case is described of presumed quinidine hepatotoxicity, characterized by the development of fever, abnormal serum transaminase values, which improved after cessation of the drug but recurred after a challenge dose, and centrizonal hepatocellular necrosis detected on liver biopsy. Morphological changes on electron microscopy, consistent with a drug reaction, are also described. Pertinent features of previous case reports are analyzed, and the histological findings by light microscopy of the present and past cases are discussed. It is suggested that the development of unexplained fever within 1 month of quinidine administration should lead to consideration of possible hepatotoxicity.", "contents": "Quinidine hepatotoxicity. A report of a case and review of the literature. A case is described of presumed quinidine hepatotoxicity, characterized by the development of fever, abnormal serum transaminase values, which improved after cessation of the drug but recurred after a challenge dose, and centrizonal hepatocellular necrosis detected on liver biopsy. Morphological changes on electron microscopy, consistent with a drug reaction, are also described. Pertinent features of previous case reports are analyzed, and the histological findings by light microscopy of the present and past cases are discussed. It is suggested that the development of unexplained fever within 1 month of quinidine administration should lead to consideration of possible hepatotoxicity."} {"id": "PMID:1269876", "title": "Piperazine hepatitis.", "content": "The first reported case of piperazine toxicity resembling viral hepatitis is described in a 25-year-old woman. The illness, which was severe, occurred after administration of the drug on two separate occasions. The evidence favors a hypersensitivity mechanism rather than a direct toxic effect of piperazine or its metabolites on the liver. The humoral or cellular immune basis for such hypersensitivity has not been elucidated.", "contents": "Piperazine hepatitis. The first reported case of piperazine toxicity resembling viral hepatitis is described in a 25-year-old woman. The illness, which was severe, occurred after administration of the drug on two separate occasions. The evidence favors a hypersensitivity mechanism rather than a direct toxic effect of piperazine or its metabolites on the liver. The humoral or cellular immune basis for such hypersensitivity has not been elucidated."} {"id": "PMID:1269877", "title": "Return of esophageal peristalsis in idiopathic achalasia.", "content": "A 47-year-old male was diagnosed as having idiopathic achalasia on the basis of clinical, roentgenographic, and manometric criteria. He was on no medication and had no disorders known to impair esophageal motility. He was treated by pneumatic dilation with a good clinical response. On reexamination 7 years later, several features considered to be typical of achalasia were no longer present. Changes included return of peristaltic activity throughout most of the body of the esophagus, failure of a direct-acting cholinergic agent to produce an increase in base line intraesophageal pressure, and failure of a direct-acting cholinergic agent to produce a heightened response at the lower esophageal sphincter (LES). Incomplete LES relaxation in response to swallowing persisted. This represents the first reported case of return of esophageal peristalsis in idiopathic achalasia.", "contents": "Return of esophageal peristalsis in idiopathic achalasia. A 47-year-old male was diagnosed as having idiopathic achalasia on the basis of clinical, roentgenographic, and manometric criteria. He was on no medication and had no disorders known to impair esophageal motility. He was treated by pneumatic dilation with a good clinical response. On reexamination 7 years later, several features considered to be typical of achalasia were no longer present. Changes included return of peristaltic activity throughout most of the body of the esophagus, failure of a direct-acting cholinergic agent to produce an increase in base line intraesophageal pressure, and failure of a direct-acting cholinergic agent to produce a heightened response at the lower esophageal sphincter (LES). Incomplete LES relaxation in response to swallowing persisted. This represents the first reported case of return of esophageal peristalsis in idiopathic achalasia."} {"id": "PMID:1269878", "title": "Rupture of a splenic artery aneurysm into the pancreatic duct.", "content": "A patient with hemorrhage into the pancreatic duct from a splenic artery aneurysm is presented. The angiographic, retrograde pancreatographic, and pathological findings are demonstrated. The diagnosis was established by demonstrating an enlarging aneurysm by serial angiograms. The location of the splenic artery aneurysm was confirmed by retrograde pancreatography before surgery. The distal pancreas containing the aneurysm was resected.", "contents": "Rupture of a splenic artery aneurysm into the pancreatic duct. A patient with hemorrhage into the pancreatic duct from a splenic artery aneurysm is presented. The angiographic, retrograde pancreatographic, and pathological findings are demonstrated. The diagnosis was established by demonstrating an enlarging aneurysm by serial angiograms. The location of the splenic artery aneurysm was confirmed by retrograde pancreatography before surgery. The distal pancreas containing the aneurysm was resected."} {"id": "PMID:1269892", "title": "[The clinical importance of magnesium during neonatal life (author's transl)].", "content": "By atomic absorption spectrophotometry (ASS) the magnesium levels in the serum of 50 mothers, their mature healthy infants and the umbilical vein and the umbilical artery were determined. The differences between maternal and neonatal levels and between umbilical vein and umbilical arteries are statistically significant. The results were as follows: Antecubital venous blood of the mother 1.41 +/- 0.38 mval/1, umbilical vein serum 1.59 +/- 0.35 mval/1, umbilical artery 1.65 +/- 0.36 mval/1, neonate 1.68 +/- 0.45 mva1/1. The magnesium concentration in the erythrocytes of neonates was determined for the first time by AAS analysis. A marked variation of the normal was found. It is possible that the determined low magnesium concentrations in the erythrocytes of neonates were due to latent magnesium deprivation in these infants. The mean values for the erythrocytes of the mother (4.38 +/- 1.16 mva1/1) and the erythrocytes from the umbilical vein (3.99 +/- 1.50 mva1/1) differed significantly, whereas the erythrocytes from the umbilical vein and from the peripheral venous blood of the neonate showed no statistically significant difference. Hypomagnesiumia and hypermagnesiumia are described in brief.", "contents": "[The clinical importance of magnesium during neonatal life (author's transl)]. By atomic absorption spectrophotometry (ASS) the magnesium levels in the serum of 50 mothers, their mature healthy infants and the umbilical vein and the umbilical artery were determined. The differences between maternal and neonatal levels and between umbilical vein and umbilical arteries are statistically significant. The results were as follows: Antecubital venous blood of the mother 1.41 +/- 0.38 mval/1, umbilical vein serum 1.59 +/- 0.35 mval/1, umbilical artery 1.65 +/- 0.36 mval/1, neonate 1.68 +/- 0.45 mva1/1. The magnesium concentration in the erythrocytes of neonates was determined for the first time by AAS analysis. A marked variation of the normal was found. It is possible that the determined low magnesium concentrations in the erythrocytes of neonates were due to latent magnesium deprivation in these infants. The mean values for the erythrocytes of the mother (4.38 +/- 1.16 mva1/1) and the erythrocytes from the umbilical vein (3.99 +/- 1.50 mva1/1) differed significantly, whereas the erythrocytes from the umbilical vein and from the peripheral venous blood of the neonate showed no statistically significant difference. Hypomagnesiumia and hypermagnesiumia are described in brief."} {"id": "PMID:1269893", "title": "[The effect of different types of oral contraceptives upon ovarian function (author's transl)].", "content": "An investigation on the influence of different types of oral contraceptives upon serum gonadotropins, estradiol and progesterone was carried out in 10 volunteers. The effect of a change from a normophasic type preparation to a sequential preparation (Ovanon and Kombiquens) and from a combined preparation to a minipill (Neogynon and Exlutona) was studied. Two new 3-phase step-up preparations were also tested. Ovulation was inhibited in each case as the preovulatory LH-peak and the subsequent rise of serum progesterone were found to be missing. The basal LH- and FSH-secretion and serum estradiol were demonstrated to be significantly diminished in the volunteers taking combined and sequential preparations. The release of gonadotropines was not inhibited as much when the 3-phase step-up preparations (SHB 261 AB and SHB 264 AB) were used. When Exlutona was taken, the basal LH-secretion was lower than during the pre- and postovulatory phase of the normal cycle, but follicular development did not appear to be inhibited much as both FSH and estradiol were found to be in the normal range.", "contents": "[The effect of different types of oral contraceptives upon ovarian function (author's transl)]. An investigation on the influence of different types of oral contraceptives upon serum gonadotropins, estradiol and progesterone was carried out in 10 volunteers. The effect of a change from a normophasic type preparation to a sequential preparation (Ovanon and Kombiquens) and from a combined preparation to a minipill (Neogynon and Exlutona) was studied. Two new 3-phase step-up preparations were also tested. Ovulation was inhibited in each case as the preovulatory LH-peak and the subsequent rise of serum progesterone were found to be missing. The basal LH- and FSH-secretion and serum estradiol were demonstrated to be significantly diminished in the volunteers taking combined and sequential preparations. The release of gonadotropines was not inhibited as much when the 3-phase step-up preparations (SHB 261 AB and SHB 264 AB) were used. When Exlutona was taken, the basal LH-secretion was lower than during the pre- and postovulatory phase of the normal cycle, but follicular development did not appear to be inhibited much as both FSH and estradiol were found to be in the normal range."} {"id": "PMID:1269894", "title": "[Clinical and morphological studies in patients with a progesterone-releasing intrauterine contraceptive device (Progestasert-System) (author's transl)].", "content": "We studied in twenty women the effectiveness of a new type of intrauterine device, which is coated with progesterone. Since the progesterone-coating is estimated to last one year, we studied the women for that period of time. None of them became pregnant. Most complained of some disturbances of menstrual bleeding during the first three months. A few experienced these disturbances for the whole year of observation. No other side effects developed like those experienced with oral contraceptives. Six hysterectomy specimens and one complete curettage became available for us to examine the histological changes produced by this new type of intrauterine device. The endometrium in all revealed a distinct division into two horizontal layers produced by progesterone absorbed from the device. The upper layer of endometrium next to the device showed a decidual change with sparse atrophic glands, like those of an arrested secretion. The underlying layer exhibited either normal proliferative or secretory changes consistent with the phase of the menstrual cycle. The remarkably circumscribed decidual change led us to refer to it as \"perifocal arrested secretion\", a term emphasizing that the gestagen inserted into the uterine cavity acts locally on the endometrium. Foci of endometrium in the myometrium (adenomyosis) are not affected.", "contents": "[Clinical and morphological studies in patients with a progesterone-releasing intrauterine contraceptive device (Progestasert-System) (author's transl)]. We studied in twenty women the effectiveness of a new type of intrauterine device, which is coated with progesterone. Since the progesterone-coating is estimated to last one year, we studied the women for that period of time. None of them became pregnant. Most complained of some disturbances of menstrual bleeding during the first three months. A few experienced these disturbances for the whole year of observation. No other side effects developed like those experienced with oral contraceptives. Six hysterectomy specimens and one complete curettage became available for us to examine the histological changes produced by this new type of intrauterine device. The endometrium in all revealed a distinct division into two horizontal layers produced by progesterone absorbed from the device. The upper layer of endometrium next to the device showed a decidual change with sparse atrophic glands, like those of an arrested secretion. The underlying layer exhibited either normal proliferative or secretory changes consistent with the phase of the menstrual cycle. The remarkably circumscribed decidual change led us to refer to it as \"perifocal arrested secretion\", a term emphasizing that the gestagen inserted into the uterine cavity acts locally on the endometrium. Foci of endometrium in the myometrium (adenomyosis) are not affected."} {"id": "PMID:1269895", "title": "[Presence of the husband in the delivery room (author's transl)].", "content": "For the past 7 years a single delivery room was available for all patients in labour. Our unit delivers approximately 1200 babies yearly. It was therefore possible to encourage the husbands progressively to be present during the delivery of their wives. Almost one half of the husbands have since been present during the delivery of their wives. The majority of the couples responded positively to the offer of the husband's presence in the delivery room. 650 couples were extensively questioned following the experience and over 90% of these couples were happy with the experience. Doubtful husbands were advised to remain. Husbands with pronounced aversion against remaining in the delivery room were not persuaded to stay. The husbands had the possibility to leave the room for short breaks and to leave the room during examinations and procedures. Delivery room clothing was supplied. For the psychic benefit of the husband, the husband was kept busy with mild services. Presence of the husband during the actual delivery of the infant was always voluntary since there was no psychologic benefit to remain during the short anaesthesia used during delivery. In many cases husbands who had not even planned to remain stayed during the actual delivery and were very impressed. Late questioning after discharge from the hospital showed that almost all couples valued the experience as positive and planned to have the husband present for the next delivery. The presence of the husband during the delivery of his infant offers a chance for the additional humanization of obstetrics which appears to be very important because of the increasing danger of depersonalization of the labour and delivery process due to the new technology. Presence of the husband during the delivery in the hospital permits a partial return to the \"idyllic\" state of domicilary obstetrics.", "contents": "[Presence of the husband in the delivery room (author's transl)]. For the past 7 years a single delivery room was available for all patients in labour. Our unit delivers approximately 1200 babies yearly. It was therefore possible to encourage the husbands progressively to be present during the delivery of their wives. Almost one half of the husbands have since been present during the delivery of their wives. The majority of the couples responded positively to the offer of the husband's presence in the delivery room. 650 couples were extensively questioned following the experience and over 90% of these couples were happy with the experience. Doubtful husbands were advised to remain. Husbands with pronounced aversion against remaining in the delivery room were not persuaded to stay. The husbands had the possibility to leave the room for short breaks and to leave the room during examinations and procedures. Delivery room clothing was supplied. For the psychic benefit of the husband, the husband was kept busy with mild services. Presence of the husband during the actual delivery of the infant was always voluntary since there was no psychologic benefit to remain during the short anaesthesia used during delivery. In many cases husbands who had not even planned to remain stayed during the actual delivery and were very impressed. Late questioning after discharge from the hospital showed that almost all couples valued the experience as positive and planned to have the husband present for the next delivery. The presence of the husband during the delivery of his infant offers a chance for the additional humanization of obstetrics which appears to be very important because of the increasing danger of depersonalization of the labour and delivery process due to the new technology. Presence of the husband during the delivery in the hospital permits a partial return to the \"idyllic\" state of domicilary obstetrics."} {"id": "PMID:1269904", "title": "Mutations masking the lambda cin-1 mutation.", "content": "A lambda cnc mutation masks the phenotype of the lambda cin-1 mutation. Eleven cnc mutations have been found. All appear to be identical and all map at a site just to the right of the cin-1 site. It is probable that cin-1 and cnc affect adjacent, or almost adjacent nucleotide pairs. Neither the cin-1 nor the cnc mutation involves large additions or deletions of genetic material.", "contents": "Mutations masking the lambda cin-1 mutation. A lambda cnc mutation masks the phenotype of the lambda cin-1 mutation. Eleven cnc mutations have been found. All appear to be identical and all map at a site just to the right of the cin-1 site. It is probable that cin-1 and cnc affect adjacent, or almost adjacent nucleotide pairs. Neither the cin-1 nor the cnc mutation involves large additions or deletions of genetic material."} {"id": "PMID:1269905", "title": "Linkage relationships and chromosome assignment of four esterase loci in the mosquito Anopheles albimanus.", "content": "Although anopheline mosquitoes are important vectors of malaria, their genetic makeup has not yet been extensively investigated. The present studies concentrate on the genetic basis of esterases in Anopheles albinomanus. Nine zones of esterase activity activity have been resolved by gel electrophoresis. Four of these esterases: EST-2, EST-4, EST-6, and EST-8 are present throughout all developmental stages and also posess allelic variation. Mass matings were carried out with homozygous males and females heterozygous for two or more loci. The analyses of the progeny from single egg batches revealed that the four esterase systems mentioned above are encoded in separate loci with codominant allels. Analyses of two-point and three-point crosses have indicated the following linkage relationships: Est-8--12%--Est-4--22%--Est-2--9%--Est-6. The assignment of this linkage group to chromosome 3 has been accomplished by the use of a Y-2 chromosome translocation.", "contents": "Linkage relationships and chromosome assignment of four esterase loci in the mosquito Anopheles albimanus. Although anopheline mosquitoes are important vectors of malaria, their genetic makeup has not yet been extensively investigated. The present studies concentrate on the genetic basis of esterases in Anopheles albinomanus. Nine zones of esterase activity activity have been resolved by gel electrophoresis. Four of these esterases: EST-2, EST-4, EST-6, and EST-8 are present throughout all developmental stages and also posess allelic variation. Mass matings were carried out with homozygous males and females heterozygous for two or more loci. The analyses of the progeny from single egg batches revealed that the four esterase systems mentioned above are encoded in separate loci with codominant allels. Analyses of two-point and three-point crosses have indicated the following linkage relationships: Est-8--12%--Est-4--22%--Est-2--9%--Est-6. The assignment of this linkage group to chromosome 3 has been accomplished by the use of a Y-2 chromosome translocation."} {"id": "PMID:1269906", "title": "Genetics of natural populations, XLIII. Further studies on rates of dispersal of Drosophila pseudoobscura and its relatives.", "content": "The amount of gene flow among local populations of a species is determined by the dispersal capacity of that species. Population samples of Drosophila pseudoobscura, D. persimilis, D. azteca, and D. miranda were collected, marked with ultraviolet fluorescent dusts, and released as soon as possible after capture. One and two days after release, recaptures were made on baits placed at 40-meter intervals in straight lines intersecting the release point. On alternative days, the baits were placed in North-South or in East-West directions. The distribution of the recaptured flies about the release point is very nearly normal. No significant differences between the dispersal rates of the four species are observed; however, males disperse slightly further than females. The variances averaged 50,822 m2 on the first day and 80,048 m2 on the second day and the estimated mean distances from the release point averaged 263 m and 361 m respectively. The genetic implications of the results are discussed.", "contents": "Genetics of natural populations, XLIII. Further studies on rates of dispersal of Drosophila pseudoobscura and its relatives. The amount of gene flow among local populations of a species is determined by the dispersal capacity of that species. Population samples of Drosophila pseudoobscura, D. persimilis, D. azteca, and D. miranda were collected, marked with ultraviolet fluorescent dusts, and released as soon as possible after capture. One and two days after release, recaptures were made on baits placed at 40-meter intervals in straight lines intersecting the release point. On alternative days, the baits were placed in North-South or in East-West directions. The distribution of the recaptured flies about the release point is very nearly normal. No significant differences between the dispersal rates of the four species are observed; however, males disperse slightly further than females. The variances averaged 50,822 m2 on the first day and 80,048 m2 on the second day and the estimated mean distances from the release point averaged 263 m and 361 m respectively. The genetic implications of the results are discussed."} {"id": "PMID:1269907", "title": "The population genetics of parthenogenetic strains of Drosophila mercatorium. II The capacity for parthenogenesis in a natural, bisexual population.", "content": "Drosophila mercatorum is a bisexual species, but certain strains are capable of parthenogenetic reproduction in the laboratory. We investigated the parthenogenetic capacity of the virgin daughters of females captured from a natural, bisexual population in Hawaii. An isozyme survey indicated the natural population is polymorphic at about 50% of its loci, and its individuals heterozygous at 18% of their loci. The predominant mode of parthogenesis in D. mercatorum causes homozygosity for all loci in a single generation. Despite this radical change in genetic state, 23% of the virgin female lines produced adult parthenogenetic progeny, and 16% produced parthenogenetic progeny themselves capable of parthenogenetic reproduction. The parthenogenetic rats as measured by the number of parthenogenetic progeny themselves capable of parthenogenesis divided by the number of eggs laid is arougn 10(-5) for the virgin female lines. We argue that one of the major reasons for this low rate is that very few of the impaternate zygotes have a genotype that can survive and reproduce under the genetic conditions imposed by parthenogenetic reproduction. This intense selective bottleneck can be passed in a single generation if enough unfertilized eggs are laid, and once passed is accompanied by a large (perhaps a thousandfold) increase in the rate of parthenogenesis and by modifications in many phenotypic traits such as morphology and behavior.", "contents": "The population genetics of parthenogenetic strains of Drosophila mercatorium. II The capacity for parthenogenesis in a natural, bisexual population. Drosophila mercatorum is a bisexual species, but certain strains are capable of parthenogenetic reproduction in the laboratory. We investigated the parthenogenetic capacity of the virgin daughters of females captured from a natural, bisexual population in Hawaii. An isozyme survey indicated the natural population is polymorphic at about 50% of its loci, and its individuals heterozygous at 18% of their loci. The predominant mode of parthogenesis in D. mercatorum causes homozygosity for all loci in a single generation. Despite this radical change in genetic state, 23% of the virgin female lines produced adult parthenogenetic progeny, and 16% produced parthenogenetic progeny themselves capable of parthenogenetic reproduction. The parthenogenetic rats as measured by the number of parthenogenetic progeny themselves capable of parthenogenesis divided by the number of eggs laid is arougn 10(-5) for the virgin female lines. We argue that one of the major reasons for this low rate is that very few of the impaternate zygotes have a genotype that can survive and reproduce under the genetic conditions imposed by parthenogenetic reproduction. This intense selective bottleneck can be passed in a single generation if enough unfertilized eggs are laid, and once passed is accompanied by a large (perhaps a thousandfold) increase in the rate of parthenogenesis and by modifications in many phenotypic traits such as morphology and behavior."} {"id": "PMID:1269908", "title": "More on Nei and Roychoudhury's sampling variances of heterozygosity and genetic distance.", "content": "The inequality relationship between the expected values of (j(x)-g)2 and (\u011d-g)2, where j(x) is a biased and \u011d is an unbiased estimate of population homozygosity g, were examined earlier by Nei and Roychoudhury (1974) and later by Mitra (1975). The improvement in the inequality still left much to be desired. In this paper a lower boundary of g has been obtained which may be regarded as ultimate for ensuring a smaller expected value of (j(x)-g)2 than the corresponding value of (\u011d-g)2.", "contents": "More on Nei and Roychoudhury's sampling variances of heterozygosity and genetic distance. The inequality relationship between the expected values of (j(x)-g)2 and (\u011d-g)2, where j(x) is a biased and \u011d is an unbiased estimate of population homozygosity g, were examined earlier by Nei and Roychoudhury (1974) and later by Mitra (1975). The improvement in the inequality still left much to be desired. In this paper a lower boundary of g has been obtained which may be regarded as ultimate for ensuring a smaller expected value of (j(x)-g)2 than the corresponding value of (\u011d-g)2."} {"id": "PMID:1269909", "title": "The effects of hitchhiking on a gene for recombination.", "content": "This paper proposes that alleles increasing recombination rates may be selected for as a result of the perturbing effects of the spread of selectively favored alleles on neighboring loci maintained polymorphic by sleection. The recombination genes are favored since their presence increases the production of selectively advantageous types of gametes with which they tend to remain associated. Numerical examples are presented, and some consequences of this model discussed. One such consequence is the wicespread existence of polymorphism for genes affecting recombination values.", "contents": "The effects of hitchhiking on a gene for recombination. This paper proposes that alleles increasing recombination rates may be selected for as a result of the perturbing effects of the spread of selectively favored alleles on neighboring loci maintained polymorphic by sleection. The recombination genes are favored since their presence increases the production of selectively advantageous types of gametes with which they tend to remain associated. Numerical examples are presented, and some consequences of this model discussed. One such consequence is the wicespread existence of polymorphism for genes affecting recombination values."} {"id": "PMID:1269910", "title": "Gamma-ray mutagenesis in bacteriophage T4.", "content": "137Cs-gamma irradiation of bacteriophage T4 induces large deletions plus a variety of types of point mutations. All mutations arise with single-hit kinetics, and all by a misrepair process. The estimated point mutation rate is 1.5 X 10(-9) per locus per rad.", "contents": "Gamma-ray mutagenesis in bacteriophage T4. 137Cs-gamma irradiation of bacteriophage T4 induces large deletions plus a variety of types of point mutations. All mutations arise with single-hit kinetics, and all by a misrepair process. The estimated point mutation rate is 1.5 X 10(-9) per locus per rad."} {"id": "PMID:1269911", "title": "On recombination between close and distant markers in phage lambda.", "content": "The contribution of parental DNA to progeny phages genetically recombinant for close markers, distant markers, or both simultaneously was studied in biparental and triparental replication-blocked crosses. The data are compatible with the previously proposed view that heterozygous overlaps at the sites of crossing over are sometimes about as long as the lambda chromosome. However, about half of the close marker recombinants have enjoyed triparental interactions, attenuating that conclusion and obscuring predictions of the long overlap model.", "contents": "On recombination between close and distant markers in phage lambda. The contribution of parental DNA to progeny phages genetically recombinant for close markers, distant markers, or both simultaneously was studied in biparental and triparental replication-blocked crosses. The data are compatible with the previously proposed view that heterozygous overlaps at the sites of crossing over are sometimes about as long as the lambda chromosome. However, about half of the close marker recombinants have enjoyed triparental interactions, attenuating that conclusion and obscuring predictions of the long overlap model."} {"id": "PMID:1269912", "title": "Suppression of the killer phenotype in Ustilago maydis.", "content": "Nineteen sensitive cell lines of U. maydis were crossed with three killer strains and sample progenies were screened for killer segregation patterns. Crosses involving 11 lines gave killer frequencies ranging from 71%-100% of the progeny and 4:0 segregations in tetrads. Segregations in some crosses involving each of the remaining 8 lines gave killer frequencies from 0%-58% and mixed tetrads containing both non-killer and killer meiotic products. Many of the killers were unstable on further culture. Killer suppression showed varying degrees of specificity, appeared to be cytoplasmically determined for at least one strain, and was associated with possession of dsRNA in this strain and one other. No dsRNA was detected in two other suppressive strains. There was no evidence for segregation of nuclear maintainer genes for any of the killer determinants.", "contents": "Suppression of the killer phenotype in Ustilago maydis. Nineteen sensitive cell lines of U. maydis were crossed with three killer strains and sample progenies were screened for killer segregation patterns. Crosses involving 11 lines gave killer frequencies ranging from 71%-100% of the progeny and 4:0 segregations in tetrads. Segregations in some crosses involving each of the remaining 8 lines gave killer frequencies from 0%-58% and mixed tetrads containing both non-killer and killer meiotic products. Many of the killers were unstable on further culture. Killer suppression showed varying degrees of specificity, appeared to be cytoplasmically determined for at least one strain, and was associated with possession of dsRNA in this strain and one other. No dsRNA was detected in two other suppressive strains. There was no evidence for segregation of nuclear maintainer genes for any of the killer determinants."} {"id": "PMID:1269913", "title": "Selection in reference to biological groups. V. Analysis of full-sib groups.", "content": "Previous studies in this series have dealt with the consequences of truncation selection operating with respect to random groups within which geno-full-sib group structure. The objective is to compare the results of individual and group selection as these methods operate on populations of random versus typic interaction may exist. The present study deal with a non-random, full-sib groups. In almost all comparisons individual selection is found to be qualitatively and quantitatively superior when used in conjunction with full-sib groups. This is due to the fact that the change in gene frequency for full-sib groups is a function of both direct and associate effects, whereas with random groups it is a function of direct effects only. With regard to group selection the efficiency is invariably superior when selection operates on non-random, full-sib rather than random groups.", "contents": "Selection in reference to biological groups. V. Analysis of full-sib groups. Previous studies in this series have dealt with the consequences of truncation selection operating with respect to random groups within which geno-full-sib group structure. The objective is to compare the results of individual and group selection as these methods operate on populations of random versus typic interaction may exist. The present study deal with a non-random, full-sib groups. In almost all comparisons individual selection is found to be qualitatively and quantitatively superior when used in conjunction with full-sib groups. This is due to the fact that the change in gene frequency for full-sib groups is a function of both direct and associate effects, whereas with random groups it is a function of direct effects only. With regard to group selection the efficiency is invariably superior when selection operates on non-random, full-sib rather than random groups."} {"id": "PMID:1269914", "title": "Selection in reference to biological groups. VI. Use of extreme forms of nonrandom groups to increase selection efficiency.", "content": "The strategy of using non-random groups to increase the efficiency of truncation selection is discussed. The present study, which considers extreme forms of non-rnadom groups, complements a previous study involving full-sib groups. It is shown that of the two kinds of non-randomness, i.e. that due to homozygosity or that due to homogeneity (as represented by cloning), the latter is the most effective. This suggests that with those plant crops in which intense competition among plants exists, use of clonal propagation to produce non-random groups should be investigated.", "contents": "Selection in reference to biological groups. VI. Use of extreme forms of nonrandom groups to increase selection efficiency. The strategy of using non-random groups to increase the efficiency of truncation selection is discussed. The present study, which considers extreme forms of non-rnadom groups, complements a previous study involving full-sib groups. It is shown that of the two kinds of non-randomness, i.e. that due to homozygosity or that due to homogeneity (as represented by cloning), the latter is the most effective. This suggests that with those plant crops in which intense competition among plants exists, use of clonal propagation to produce non-random groups should be investigated."} {"id": "PMID:1269915", "title": "Alcohol dehydrogenase-negative mutants in Drosophila: defects at the structural locus?", "content": "Sixteen Adh-negative mutants (induced by ethyl methanesulfonate) were examined for the presence of inactive alcohol dehydrogenase (ADH) protein. Four techniques were utilized in an effort to detect this protein: hybrid enzyme formation, intra-cistronic complentation, sodium dodecyl sulfate electrophoresis and antibody precipitation. Eleven of the sixteen negative strains showed evidence of inactive ADH protein and are preseumably mutations in the strutural element. These results are discussed in light of some recent models of gene organization in higher organisms.", "contents": "Alcohol dehydrogenase-negative mutants in Drosophila: defects at the structural locus? Sixteen Adh-negative mutants (induced by ethyl methanesulfonate) were examined for the presence of inactive alcohol dehydrogenase (ADH) protein. Four techniques were utilized in an effort to detect this protein: hybrid enzyme formation, intra-cistronic complentation, sodium dodecyl sulfate electrophoresis and antibody precipitation. Eleven of the sixteen negative strains showed evidence of inactive ADH protein and are preseumably mutations in the strutural element. These results are discussed in light of some recent models of gene organization in higher organisms."} {"id": "PMID:1269916", "title": "Galactokinase mutants of Chinese hamster somatic cells resistant to 2-deoxygalactose.", "content": "The growth of Chinese hamster somatic cells was inhibited by 0.2 mg/cc of 2-deoxygalactose. Mutants partially or fully resistant to 2-deoxygalactose were isolated in a single-step or two-step selection. Some of them did not grow as well as the wild type; one of them which lacked galactokinase(EC.2.7.1.6) activity did not grow at all in galactose medium. The galactokinase kinetic properties (Vmax & kmax of the other mutants and of the wild type were different. Therefore resistance resulted either from the possible absence of galactokinase synthesis or from a structural mutation, possible a missence mutation, in the galactokinase gene.- A simple diagnostic test for juvenile cataract is proposed.", "contents": "Galactokinase mutants of Chinese hamster somatic cells resistant to 2-deoxygalactose. The growth of Chinese hamster somatic cells was inhibited by 0.2 mg/cc of 2-deoxygalactose. Mutants partially or fully resistant to 2-deoxygalactose were isolated in a single-step or two-step selection. Some of them did not grow as well as the wild type; one of them which lacked galactokinase(EC.2.7.1.6) activity did not grow at all in galactose medium. The galactokinase kinetic properties (Vmax & kmax of the other mutants and of the wild type were different. Therefore resistance resulted either from the possible absence of galactokinase synthesis or from a structural mutation, possible a missence mutation, in the galactokinase gene.- A simple diagnostic test for juvenile cataract is proposed."} {"id": "PMID:1269917", "title": "Hidden alleles at the alpha-glycerophosphate dehydrogenase locus in Colias butterflies.", "content": "By varying polyacrylamide gel pore size, the alpha-glycerophosphate dehydrogenase locus of Colias butterflies is shown to contain at least five alkeles, rather than the two which had been reported previously. Two of the alleles have the same apparent net charge, and presumably are detected electrophoretically because of the conformational differences. Additional variation occurs in the isoelectric points of the proteins. It is suggested that electrophoresis employing a single gel of intermediated pore size will fail to discriminate between many alleles, and that the concept of electrophoretic alleles as differing simply in charge may not always be appropriate.", "contents": "Hidden alleles at the alpha-glycerophosphate dehydrogenase locus in Colias butterflies. By varying polyacrylamide gel pore size, the alpha-glycerophosphate dehydrogenase locus of Colias butterflies is shown to contain at least five alkeles, rather than the two which had been reported previously. Two of the alleles have the same apparent net charge, and presumably are detected electrophoretically because of the conformational differences. Additional variation occurs in the isoelectric points of the proteins. It is suggested that electrophoresis employing a single gel of intermediated pore size will fail to discriminate between many alleles, and that the concept of electrophoretic alleles as differing simply in charge may not always be appropriate."} {"id": "PMID:1269918", "title": "The distribution of enzyme and inversion polymorphism over the genome of Drosophila: evidence against balancing selection.", "content": "In species of repleta group of Drosophila about 70% of the electrophoretic variability is absorbed by the same chromosome which absorbs about 70% of the cytological variability of the group. However, this does not imply that inversions are actively involved in the maintenance of protein variation. A comparison of cytological and electrophoretic variation of homologous chromosomes points out that the amount of cytological polymorphism varies greatly over species of Drosophila while electrophoretic variation does not. This suggests that allelozymes do not constitute part of the coadapted complexes of genes characterizing the inversions. Rather, the amount of electropheptide molecule and is largely independent of factors such as background genotype and differences in the environment.", "contents": "The distribution of enzyme and inversion polymorphism over the genome of Drosophila: evidence against balancing selection. In species of repleta group of Drosophila about 70% of the electrophoretic variability is absorbed by the same chromosome which absorbs about 70% of the cytological variability of the group. However, this does not imply that inversions are actively involved in the maintenance of protein variation. A comparison of cytological and electrophoretic variation of homologous chromosomes points out that the amount of cytological polymorphism varies greatly over species of Drosophila while electrophoretic variation does not. This suggests that allelozymes do not constitute part of the coadapted complexes of genes characterizing the inversions. Rather, the amount of electropheptide molecule and is largely independent of factors such as background genotype and differences in the environment."} {"id": "PMID:1269919", "title": "Recombination modification in a flucturating environment.", "content": "This paper examines the theory of the evolution of increased recombination between two loci subjected to interactive selection in a temporally fluctuating environment. Both cyclical and stochastic environments are considered. It is shown that temporal variation in the linkage disequilibrium coefficient for the pair of selected loci, due to fluctuations in the selective values of the genotypes at these loci, can give rise to selection in favor of modifier genes increasing recombination. The equilibrium level of recombination established in a given population depends on several factors; it is highest for intermediate values of the environmental periodicity or autocorrelation, for cases when the modifier genes are themselves linked to the selected loci, and for high levels of environmental variation. In general, it seems that the rate of modification of recombination values by this process will be low except when the modifiers are tightly linked to the selected loci. The possible evolutionary significance of this process is discussed in relation to observations on genetic systems of plants and animals.", "contents": "Recombination modification in a flucturating environment. This paper examines the theory of the evolution of increased recombination between two loci subjected to interactive selection in a temporally fluctuating environment. Both cyclical and stochastic environments are considered. It is shown that temporal variation in the linkage disequilibrium coefficient for the pair of selected loci, due to fluctuations in the selective values of the genotypes at these loci, can give rise to selection in favor of modifier genes increasing recombination. The equilibrium level of recombination established in a given population depends on several factors; it is highest for intermediate values of the environmental periodicity or autocorrelation, for cases when the modifier genes are themselves linked to the selected loci, and for high levels of environmental variation. In general, it seems that the rate of modification of recombination values by this process will be low except when the modifiers are tightly linked to the selected loci. The possible evolutionary significance of this process is discussed in relation to observations on genetic systems of plants and animals."} {"id": "PMID:1269920", "title": "Further studies on the ribosomal RNA cistrons of Sciara coprophila (Diptera).", "content": "Additional experiments with homologous as well as heterologous hybridization confirmed our previous finding in Sciara coprophila that XX females have nearly twice the number of ribosomal RNA cistrons as XO males. A comparison between two different X' chromosomes revealed that only the one carrying the irradiation-induced Wavy mutation has a deletion of 70% of its ribosomal RNA cistrons as compared to the standard X. The deletion is relatively stable, and the remaining ribosomal RNA cistrons donot appear to undergo disproportionate replication or magnification as in Drosophila. Homologous hybridization experiments revealed an unusually low reiteration of ribosomal RNA cistrons in this fly, 45 gene copies per X chromosome. The question is raised as to whether such a low number of cistrons may be related to the unusual nucleolar condition encountered in the Sciaridae.", "contents": "Further studies on the ribosomal RNA cistrons of Sciara coprophila (Diptera). Additional experiments with homologous as well as heterologous hybridization confirmed our previous finding in Sciara coprophila that XX females have nearly twice the number of ribosomal RNA cistrons as XO males. A comparison between two different X' chromosomes revealed that only the one carrying the irradiation-induced Wavy mutation has a deletion of 70% of its ribosomal RNA cistrons as compared to the standard X. The deletion is relatively stable, and the remaining ribosomal RNA cistrons donot appear to undergo disproportionate replication or magnification as in Drosophila. Homologous hybridization experiments revealed an unusually low reiteration of ribosomal RNA cistrons in this fly, 45 gene copies per X chromosome. The question is raised as to whether such a low number of cistrons may be related to the unusual nucleolar condition encountered in the Sciaridae."} {"id": "PMID:1269921", "title": "Chromosome rearrangements in Caenorhabditis elegans.", "content": "A method for selecting unlinked duplications of a part of the X chromosome of C. elegans is described. Five such duplications have been identified. One of them, Dp (X;V)1, is translocated to linkage group V, where it suppresses crossing over along the left half of linkage group V. Dp(X;V)1 homozygotes grow slowly and are sterile. The other four duplications are associated with chromosome fragments, as observed cytologically by fluorescence microscopy, and tend to be lost. Their frequency of loss is higher in strains homozygous for a mutation that promotes nondisjunction of X chromosomes. The recombination frequencies between two of these duplications and the X have been measured: the frequencies are at least 50 times less than for X-X recombination in the same region. The duplications may prove useful as balancers of recessive lethal mutations.", "contents": "Chromosome rearrangements in Caenorhabditis elegans. A method for selecting unlinked duplications of a part of the X chromosome of C. elegans is described. Five such duplications have been identified. One of them, Dp (X;V)1, is translocated to linkage group V, where it suppresses crossing over along the left half of linkage group V. Dp(X;V)1 homozygotes grow slowly and are sterile. The other four duplications are associated with chromosome fragments, as observed cytologically by fluorescence microscopy, and tend to be lost. Their frequency of loss is higher in strains homozygous for a mutation that promotes nondisjunction of X chromosomes. The recombination frequencies between two of these duplications and the X have been measured: the frequencies are at least 50 times less than for X-X recombination in the same region. The duplications may prove useful as balancers of recessive lethal mutations."} {"id": "PMID:1269922", "title": "[Dynamics of population genetics parameters and their statistical during assessment selection for quantitative characters. I. An additive model. One character].", "content": "The selection for a single additively inherited quantitative character is studied using computer models of 3 types: 1) all the individuals had the same viability, and the paratypic deviation does not depend on their genotype; 2) differential viability of genotypes is taken into account with respect to a number of heterozygous loci; 3) differential paratypic deviation is estimated, it is introduced like viability in the model 2. Two types of trancation selection, stabilizing and directed, under the selection coefficient of approximately 0.5 are studied. There are studied dynamics of genotypic (omega2gamma) and phenotypic (omega2phi) variances, the heritability index and it estimates (for the correlation progeny-parent--rho; for the regression progeny-parent--b; for half-sibses--v), and the non-equilibrium of a population for the models. The number of generation was 10; the population number in every generation was 200; the number of loci in the main experiment was 10.h2 values were calculated in the progeny before selection (p1, b1, v1) and after selection (p2, b2, v2). It is shown that stabilizing selection results in the formation of balanced gene complexes; the rate of decreasing omega2phi depends on the genetic length of a chromosome region in which genes, determining the character, are located, and not on the number of genes. The distribution of a character under directed selection depends on the type of the model. p2, b2, and v2 values are the worst. The best is the b1 value. It is concluded that the problem of predicting the selection effect using statistical estimates of heretability is connected with the problem of investigation of population heterogeneity and integrating their genetical structure.", "contents": "[Dynamics of population genetics parameters and their statistical during assessment selection for quantitative characters. I. An additive model. One character]. The selection for a single additively inherited quantitative character is studied using computer models of 3 types: 1) all the individuals had the same viability, and the paratypic deviation does not depend on their genotype; 2) differential viability of genotypes is taken into account with respect to a number of heterozygous loci; 3) differential paratypic deviation is estimated, it is introduced like viability in the model 2. Two types of trancation selection, stabilizing and directed, under the selection coefficient of approximately 0.5 are studied. There are studied dynamics of genotypic (omega2gamma) and phenotypic (omega2phi) variances, the heritability index and it estimates (for the correlation progeny-parent--rho; for the regression progeny-parent--b; for half-sibses--v), and the non-equilibrium of a population for the models. The number of generation was 10; the population number in every generation was 200; the number of loci in the main experiment was 10.h2 values were calculated in the progeny before selection (p1, b1, v1) and after selection (p2, b2, v2). It is shown that stabilizing selection results in the formation of balanced gene complexes; the rate of decreasing omega2phi depends on the genetic length of a chromosome region in which genes, determining the character, are located, and not on the number of genes. The distribution of a character under directed selection depends on the type of the model. p2, b2, and v2 values are the worst. The best is the b1 value. It is concluded that the problem of predicting the selection effect using statistical estimates of heretability is connected with the problem of investigation of population heterogeneity and integrating their genetical structure."} {"id": "PMID:1269923", "title": "[Genetic polymorphism of the serum transferrins of the northern reindeer (Rangifer tarandus L.) of northwestern Siberia].", "content": "On the basis of the examination of random samples of seven populations of reindeer inhabiting the Montane-Taiga Zone and of nine population inhabiting the Tundra Zone of the Magadan Region 8 alleles of transferrin locus described earlier (TfA, TfC, TfE, TfG, TfH, TfJ, TfK and TfM) were identified and the ninth hitherto unknown allele (TfN) was discovered. Gene concentrations of all these alleles in populations studies were determined. The reindeer of the North-East of Siberia differ in frequencies of Tf alleles from those of Norway and, apparently, also from the reindeer inhabiting the northern regions of the European part of the USSR and from the American caribou. The allele TfK is possibly associated with the resistance of reindeer to necrobacteriosis.", "contents": "[Genetic polymorphism of the serum transferrins of the northern reindeer (Rangifer tarandus L.) of northwestern Siberia]. On the basis of the examination of random samples of seven populations of reindeer inhabiting the Montane-Taiga Zone and of nine population inhabiting the Tundra Zone of the Magadan Region 8 alleles of transferrin locus described earlier (TfA, TfC, TfE, TfG, TfH, TfJ, TfK and TfM) were identified and the ninth hitherto unknown allele (TfN) was discovered. Gene concentrations of all these alleles in populations studies were determined. The reindeer of the North-East of Siberia differ in frequencies of Tf alleles from those of Norway and, apparently, also from the reindeer inhabiting the northern regions of the European part of the USSR and from the American caribou. The allele TfK is possibly associated with the resistance of reindeer to necrobacteriosis."} {"id": "PMID:1269925", "title": "[Comparative characteristics of phenotypes in numerical anomalies of human X-chromosomes (morphologic and psychological features)].", "content": "On the basis of data on antropological and psychological investigation of 30 XXY males, 30 X0 females and 10 XXX females comparative characteristics of phenotypes of patients are given. The persons with X monosomy (the absence X- or Y-chromosomes) are observed to have decreased total sizes of body, to retain the ability to compensate congenital mental defects, to use standard methods of the adaptation to social environment and to assimilate standard norms of social behaviour. The persons with trisomies XXY and XXX (the presence of the additional heterochromatic X-chromosome) have the tendency to an increase of the longitudinal body sizes independently on sex; they have a delayed development of mental functions and reduced possibilities to compensation of these functions; they also have different degrees of disorganization of the social behaviour and the disadaptation to social environment. It is found that the patients with numerical anomalies of human X-chromosome (both the lack and the excess of chromosome material) have a disturbance of development of the sex dimorphism and sex dipsychism.", "contents": "[Comparative characteristics of phenotypes in numerical anomalies of human X-chromosomes (morphologic and psychological features)]. On the basis of data on antropological and psychological investigation of 30 XXY males, 30 X0 females and 10 XXX females comparative characteristics of phenotypes of patients are given. The persons with X monosomy (the absence X- or Y-chromosomes) are observed to have decreased total sizes of body, to retain the ability to compensate congenital mental defects, to use standard methods of the adaptation to social environment and to assimilate standard norms of social behaviour. The persons with trisomies XXY and XXX (the presence of the additional heterochromatic X-chromosome) have the tendency to an increase of the longitudinal body sizes independently on sex; they have a delayed development of mental functions and reduced possibilities to compensation of these functions; they also have different degrees of disorganization of the social behaviour and the disadaptation to social environment. It is found that the patients with numerical anomalies of human X-chromosome (both the lack and the excess of chromosome material) have a disturbance of development of the sex dimorphism and sex dipsychism."} {"id": "PMID:1269927", "title": "[Cystamine and the chromosome vesting phenomenon].", "content": "The effect of radioprotector cystamine on structural chromosome mutations induced in Crepis capillaris cells by gamma-rays 137Cs is studied. Cystamine at the concentration of 0,1% causes a two-fold decrease in the frequency of structural mutations. In the \"vesting\" phenomenon of ring chromosomes, under the same experimental conditions, it also leads to a two-fold decrease in the frequency of exchanges, in relation to the frequency of fragment units in the initial stage, by repair of normal chromosome structure. Cystamine provides protection in structural mutagenesis at the moment of realization of primary mutagenic changes into mutations due to enzyme ligazing chromosome fragments.", "contents": "[Cystamine and the chromosome vesting phenomenon]. The effect of radioprotector cystamine on structural chromosome mutations induced in Crepis capillaris cells by gamma-rays 137Cs is studied. Cystamine at the concentration of 0,1% causes a two-fold decrease in the frequency of structural mutations. In the \"vesting\" phenomenon of ring chromosomes, under the same experimental conditions, it also leads to a two-fold decrease in the frequency of exchanges, in relation to the frequency of fragment units in the initial stage, by repair of normal chromosome structure. Cystamine provides protection in structural mutagenesis at the moment of realization of primary mutagenic changes into mutations due to enzyme ligazing chromosome fragments."} {"id": "PMID:1269928", "title": "[Undulating kinetics factors in radiation mutagenesis].", "content": "Air-dry Crepis capillaris seeds, soaked for 14 and 20 hours, were dried to the moisture content of 1,1% with the following gamma-irradiation at a dose of 1500 r. Irradiated seeds were stored in the state of identical moisture for 38 days. The drying of three groups of seeds to moisture content of 1,1% provided their identical initial radiosensitivity. In the course of the storage mutability of treated seeds significantly increased as compared with the yield of mutations in non-stored seeds, and revealed undulating kinetics that involved all types of arising chromosome and chromatid rearrangements. The character of undulating kinetics is due to a correlation between functional state of nucleus (early G1, late G1, S) and water content in seeds.", "contents": "[Undulating kinetics factors in radiation mutagenesis]. Air-dry Crepis capillaris seeds, soaked for 14 and 20 hours, were dried to the moisture content of 1,1% with the following gamma-irradiation at a dose of 1500 r. Irradiated seeds were stored in the state of identical moisture for 38 days. The drying of three groups of seeds to moisture content of 1,1% provided their identical initial radiosensitivity. In the course of the storage mutability of treated seeds significantly increased as compared with the yield of mutations in non-stored seeds, and revealed undulating kinetics that involved all types of arising chromosome and chromatid rearrangements. The character of undulating kinetics is due to a correlation between functional state of nucleus (early G1, late G1, S) and water content in seeds."} {"id": "PMID:1269933", "title": "Ambulation and self-care are goals of rehabilitation after stroke.", "content": "Successful rehabilitation of the elderly hemiplegic patient means achievement of ambulation of self-care. The patient's potential for reaching this goal can be determined shortly after the stroke by the stand-up test. Delay of an adequate rehabilitation program, often caused by administrative obstacles to proper care, decreases the potential. Rehabilitation of the elderly hemiplegic also is often hampered by impairment of communication. However, with correction of organic abnormalities causing mental disturbance and with use of simple techniques to facilitate communication, it is possible to achieve ambulation even in patients with marginal ability to communicate.", "contents": "Ambulation and self-care are goals of rehabilitation after stroke. Successful rehabilitation of the elderly hemiplegic patient means achievement of ambulation of self-care. The patient's potential for reaching this goal can be determined shortly after the stroke by the stand-up test. Delay of an adequate rehabilitation program, often caused by administrative obstacles to proper care, decreases the potential. Rehabilitation of the elderly hemiplegic also is often hampered by impairment of communication. However, with correction of organic abnormalities causing mental disturbance and with use of simple techniques to facilitate communication, it is possible to achieve ambulation even in patients with marginal ability to communicate."} {"id": "PMID:1269935", "title": "Aging of the neuromuscular apparatus.", "content": "With age marked changes in metabolism and function of muscle fibers appear: electroexcitability thresholds rise, critical polarization level and membrane resistance decrease, time of action potential increases and its amplitude decreases, lability is reduced. The level of intracellular sodium increases and that of potassium decreases. Shifts in ionic asymmetry of muscle fibers are connected with changes in their membrane permeability and a modified function of the sodium-potassium pump. Along with the impairment of nervous influences on muscle fibers in old age, their sensitivity to many hormonal factors increases. Loading levels all age differences in the regulation of skeletal muscle vascular tone. The relationships between the activity of the genetic apparatus and electrical properties of the cell are altered.", "contents": "Aging of the neuromuscular apparatus. With age marked changes in metabolism and function of muscle fibers appear: electroexcitability thresholds rise, critical polarization level and membrane resistance decrease, time of action potential increases and its amplitude decreases, lability is reduced. The level of intracellular sodium increases and that of potassium decreases. Shifts in ionic asymmetry of muscle fibers are connected with changes in their membrane permeability and a modified function of the sodium-potassium pump. Along with the impairment of nervous influences on muscle fibers in old age, their sensitivity to many hormonal factors increases. Loading levels all age differences in the regulation of skeletal muscle vascular tone. The relationships between the activity of the genetic apparatus and electrical properties of the cell are altered."} {"id": "PMID:1269936", "title": "Fast and slow motor units in ageing.", "content": "The differences in onset and degree of old age changes in different muscles are explained by the differentiation and different reactivity of fast and slow motor units with respect to physiological, structural and biochemical characteristics. The main changes in the motor units in old age are described. The general basic change is a progressive random disturbance of neuromuscular contact ascribed to a decrease of the trophic function of the neuron. The main motor disturbances in old age, i.e; slowness, decrease of muscle strength and lack of fine coordination are explained in terms of physiological changes in senescent motor units. The reactions of senescent motor units differ from one unit to another as shown, e.g. in denervation, reinnervation and regeneration (transplantation) studies. The trend to a shift from a heterogeneous to a more uniform muscle fibre pattern and the defficiencies in recovery of the original muscle fibre pattern in reinnervation and regeneration of senescent muscle is demonstrated and explained by a decrease of the differentiating capacity of different motor units. The changes in the heterogeneous fibre pattern of skeletal and the homogeneous fibre pattern of the papillary heart muscle in old age are contrasted.", "contents": "Fast and slow motor units in ageing. The differences in onset and degree of old age changes in different muscles are explained by the differentiation and different reactivity of fast and slow motor units with respect to physiological, structural and biochemical characteristics. The main changes in the motor units in old age are described. The general basic change is a progressive random disturbance of neuromuscular contact ascribed to a decrease of the trophic function of the neuron. The main motor disturbances in old age, i.e; slowness, decrease of muscle strength and lack of fine coordination are explained in terms of physiological changes in senescent motor units. The reactions of senescent motor units differ from one unit to another as shown, e.g. in denervation, reinnervation and regeneration (transplantation) studies. The trend to a shift from a heterogeneous to a more uniform muscle fibre pattern and the defficiencies in recovery of the original muscle fibre pattern in reinnervation and regeneration of senescent muscle is demonstrated and explained by a decrease of the differentiating capacity of different motor units. The changes in the heterogeneous fibre pattern of skeletal and the homogeneous fibre pattern of the papillary heart muscle in old age are contrasted."} {"id": "PMID:1269937", "title": "Aging changes in insect flight muscle.", "content": "Age-associated changes in the flight muscles of higher insects, using male housefly as an example, have been discussed. The duration of sustained flight activity declines with age. During the first trimester of adult life, the mitochondrial volume in the flight muscles increases by additional biosynthesis. Individual mitochondria become further enlarged by the fusion of adjacent organelles. In old flies, a small proportion of mitochondria show degenerative changes. In senile flies, focal areas of the flight muscles undergo cytolytic changes. A variety of metabolic changes involving enzyme activities, protein synthesis, substrate levels and bioenergetics have been reported in flight muscles of aging insects. The mechanism of the loss in flight capacity of old insects, however, remains unknown.", "contents": "Aging changes in insect flight muscle. Age-associated changes in the flight muscles of higher insects, using male housefly as an example, have been discussed. The duration of sustained flight activity declines with age. During the first trimester of adult life, the mitochondrial volume in the flight muscles increases by additional biosynthesis. Individual mitochondria become further enlarged by the fusion of adjacent organelles. In old flies, a small proportion of mitochondria show degenerative changes. In senile flies, focal areas of the flight muscles undergo cytolytic changes. A variety of metabolic changes involving enzyme activities, protein synthesis, substrate levels and bioenergetics have been reported in flight muscles of aging insects. The mechanism of the loss in flight capacity of old insects, however, remains unknown."} {"id": "PMID:1269938", "title": "Insect flight muscle: maturation and senescence.", "content": "That holometabolous insects undergo a number of post-emergent morphological, physiological, and biochemical maturational processes, termed metachemogenesis, is unquestionable. This is readily evident as regards the capacity for flight. The maturational processes demonstrated in mitochondria and/or mitochondrial enzyme systems, myofibrils, as well as other biochemical systems have been sufficiently documented in a number of species, directly correlated with the attainment of optimal flight ability in terms of both wing beat frequency and the duration of sustained flight; suggesting that the phenomena is a general one, particularly in the orders Diptera and Hymenoptera. Subsequent to the time-dependent maturational processes which are species-specific, there is an observed relatively stable period of flight performance during adult life. With advancing age, flight performance declines, most noticeably in the duration of sustained flight. This diminution, as the maturation of flight ability, is also correlated with a decline in a number of biochemical parameters, i.e. levels of and/or ability to utilize glycogen, various enzyme systems, mitochondrial efficiency, particularly in dipteran insects. Furthermore, as the morphological degenerative changes observed in aging flight muscle are variable and do not appear to be of sufficient magnitude to account for the substantial decline in the physiological expression of flight, one may assume that neurophysiological and/or biochemical mechanisms are responsible. A more fundamental question as regards the mechanisms of agins is whether or not the decrease in flight performance with advancing age is due to random error, or is in some way genetically controlled as the post-emergent maturational changes must be. The orderly sequential pattern of enzyme changes associated with the maturation and senescence of flight ability, particularly in the male housefly, and the demonstration of an identical sequential pattern of change in two of these enzymes, again correlated with the maturation and decline in flight performance in two other dipteran insects, suggest that the senescence of flight ability may also be manifested in an orderly programmed manner.", "contents": "Insect flight muscle: maturation and senescence. That holometabolous insects undergo a number of post-emergent morphological, physiological, and biochemical maturational processes, termed metachemogenesis, is unquestionable. This is readily evident as regards the capacity for flight. The maturational processes demonstrated in mitochondria and/or mitochondrial enzyme systems, myofibrils, as well as other biochemical systems have been sufficiently documented in a number of species, directly correlated with the attainment of optimal flight ability in terms of both wing beat frequency and the duration of sustained flight; suggesting that the phenomena is a general one, particularly in the orders Diptera and Hymenoptera. Subsequent to the time-dependent maturational processes which are species-specific, there is an observed relatively stable period of flight performance during adult life. With advancing age, flight performance declines, most noticeably in the duration of sustained flight. This diminution, as the maturation of flight ability, is also correlated with a decline in a number of biochemical parameters, i.e. levels of and/or ability to utilize glycogen, various enzyme systems, mitochondrial efficiency, particularly in dipteran insects. Furthermore, as the morphological degenerative changes observed in aging flight muscle are variable and do not appear to be of sufficient magnitude to account for the substantial decline in the physiological expression of flight, one may assume that neurophysiological and/or biochemical mechanisms are responsible. A more fundamental question as regards the mechanisms of agins is whether or not the decrease in flight performance with advancing age is due to random error, or is in some way genetically controlled as the post-emergent maturational changes must be. The orderly sequential pattern of enzyme changes associated with the maturation and senescence of flight ability, particularly in the male housefly, and the demonstration of an identical sequential pattern of change in two of these enzymes, again correlated with the maturation and decline in flight performance in two other dipteran insects, suggest that the senescence of flight ability may also be manifested in an orderly programmed manner."} {"id": "PMID:1269974", "title": "Hepatitis B antigen (HBSAg) and/or antibodies (anti-HBS and anti-HBC) in fulminant hepatitis: pathogenic and prognostic significance.", "content": "Hepatitis B surface antigen (HBSAg) and antibodies to both the surface and core antigens of the hepatitis B virus (anti-HBS and anti-HBC) have been studied in 64 consecutive cases of fulminant hepatitis. HBSAg was detected by counterelectrophoresis in 23 (35-9%) but by radioimmunoassay in 38 (59-3%). Anti-HBS was detected by passive haemagglutination in 26 (40-6%), coexisting HBSAg and anti-HBS were found in 16 cases (25%). Using an indirect immunofluorescence technique, anti-HBC was found in all of the cases in whom either HBSAg or anti-HBS was present. The highest survival rate was observed in patients with no evidence of HBV infection (31-3%) and was lowest in those who had both HBSAg and anti-HBS detected simultaneously (6-2%). The prognosis of those who exhibited anti-HBS only was no better than those with HBSAg alone. In a further case, transient interruption of the asymptomatic chronic HBSAg carrier state with seroconversion to anti-HBS was associated with the development of a fulminant hepatitis syndrome. The results suggest that an unusually strong and rapid immune clearance of HBSAg may be involved in the pathogenesis of fulminant hepatitis.", "contents": "Hepatitis B antigen (HBSAg) and/or antibodies (anti-HBS and anti-HBC) in fulminant hepatitis: pathogenic and prognostic significance. Hepatitis B surface antigen (HBSAg) and antibodies to both the surface and core antigens of the hepatitis B virus (anti-HBS and anti-HBC) have been studied in 64 consecutive cases of fulminant hepatitis. HBSAg was detected by counterelectrophoresis in 23 (35-9%) but by radioimmunoassay in 38 (59-3%). Anti-HBS was detected by passive haemagglutination in 26 (40-6%), coexisting HBSAg and anti-HBS were found in 16 cases (25%). Using an indirect immunofluorescence technique, anti-HBC was found in all of the cases in whom either HBSAg or anti-HBS was present. The highest survival rate was observed in patients with no evidence of HBV infection (31-3%) and was lowest in those who had both HBSAg and anti-HBS detected simultaneously (6-2%). The prognosis of those who exhibited anti-HBS only was no better than those with HBSAg alone. In a further case, transient interruption of the asymptomatic chronic HBSAg carrier state with seroconversion to anti-HBS was associated with the development of a fulminant hepatitis syndrome. The results suggest that an unusually strong and rapid immune clearance of HBSAg may be involved in the pathogenesis of fulminant hepatitis."} {"id": "PMID:1269975", "title": "Assessment of endoscopic retrograde cholangio-pancreatography (ERCP) and pure pancreatic juice cytology in patients with pancreatic disease.", "content": "Pure pancreatic juice has been collected from 61 patients at the time of endoscopic retrograde cholangio-pancreatography (ERCP) for the purpose of cytodiagnosis. The ERCP and cytological findings are discussed. Pure pancreatic juice cytology may help in the interpretation of the pancreatogram in both pancreatitis and pancreatic carcinoma. In patients with pancreatic carcinoma, ERCP alone was diagnostic in 65%, cytology alone in 54%. By combining these two approaches, a diagnostic result was obtained in 92% of patients.", "contents": "Assessment of endoscopic retrograde cholangio-pancreatography (ERCP) and pure pancreatic juice cytology in patients with pancreatic disease. Pure pancreatic juice has been collected from 61 patients at the time of endoscopic retrograde cholangio-pancreatography (ERCP) for the purpose of cytodiagnosis. The ERCP and cytological findings are discussed. Pure pancreatic juice cytology may help in the interpretation of the pancreatogram in both pancreatitis and pancreatic carcinoma. In patients with pancreatic carcinoma, ERCP alone was diagnostic in 65%, cytology alone in 54%. By combining these two approaches, a diagnostic result was obtained in 92% of patients."} {"id": "PMID:1269976", "title": "Prostaglandin release in canine acute haemorrhagic pancreatitis.", "content": "Acute haemorrhagic pancreatitis was induced in greyhound dogs by a bile salt/trypsin injection into the main pancreatic duct. Prostaglandin-like activity in the pancreatic venous blood, right atrial blood, and arterial blood was measured by bioassay. Activity rose significantly in the pancreatic venous blood of test dogs but not in controls. Chromatographic analysis of the peritoneal exudate from the dogs with pancreatitis showed high levels of prostaglandin E-like material (mean 43 ng/ml prostaglandin E2 equivalents). It seems likely that prostaglandins contribute to the induced pancreatitis.", "contents": "Prostaglandin release in canine acute haemorrhagic pancreatitis. Acute haemorrhagic pancreatitis was induced in greyhound dogs by a bile salt/trypsin injection into the main pancreatic duct. Prostaglandin-like activity in the pancreatic venous blood, right atrial blood, and arterial blood was measured by bioassay. Activity rose significantly in the pancreatic venous blood of test dogs but not in controls. Chromatographic analysis of the peritoneal exudate from the dogs with pancreatitis showed high levels of prostaglandin E-like material (mean 43 ng/ml prostaglandin E2 equivalents). It seems likely that prostaglandins contribute to the induced pancreatitis."} {"id": "PMID:1269977", "title": "Oral administration of a chymotrypsin-labile peptide--a new test of exocrine pancreatic function in man (PFT).", "content": "One gram N-benzoyl-L-tyrosyl PABA was orally administered to 24 controls, 15 patients with chronic exocrine pancreatic disease, 13 patients after an attack of acute pancreatitis, two patients with gluten-sensitive enteropathy, and 10 patients with biliary tract disease, peptic ulcer, or other pathology of the gastrointestinal tract. In the presence of chymotrypsin, PABA is split from the peptide and excreted in the urine. The amount of PABA excreted serves as a parameter of exocrine pancreatic function. In 51 patients, exocrine pancreatic secretion was also assessed by the Lundh test. In the control group a mean of 59-6 +/- 12-2% (mean +/- 2 SD) of the peptide-PABA was excreted over a period of six hours. PABA excretion in exocrine pancreatic deficiency was significantly less (P less than 0.001) than in controls. With one exception no overlap of data was noted. In the group with exocrine pancreatic deficiency, a significant relationship was shown between the PFT and the Lundh test. Reproducibility in duplicate test was excellent. The present data justify further investigations of this procedure as a possible new oral test of exocrine pancreatic function.", "contents": "Oral administration of a chymotrypsin-labile peptide--a new test of exocrine pancreatic function in man (PFT). One gram N-benzoyl-L-tyrosyl PABA was orally administered to 24 controls, 15 patients with chronic exocrine pancreatic disease, 13 patients after an attack of acute pancreatitis, two patients with gluten-sensitive enteropathy, and 10 patients with biliary tract disease, peptic ulcer, or other pathology of the gastrointestinal tract. In the presence of chymotrypsin, PABA is split from the peptide and excreted in the urine. The amount of PABA excreted serves as a parameter of exocrine pancreatic function. In 51 patients, exocrine pancreatic secretion was also assessed by the Lundh test. In the control group a mean of 59-6 +/- 12-2% (mean +/- 2 SD) of the peptide-PABA was excreted over a period of six hours. PABA excretion in exocrine pancreatic deficiency was significantly less (P less than 0.001) than in controls. With one exception no overlap of data was noted. In the group with exocrine pancreatic deficiency, a significant relationship was shown between the PFT and the Lundh test. Reproducibility in duplicate test was excellent. The present data justify further investigations of this procedure as a possible new oral test of exocrine pancreatic function."} {"id": "PMID:1269978", "title": "Review of five cases of early gastric carcinoma.", "content": "Five cases of early gastric carcinoma (EGC) were seen in 12 months. The clinical features did not provide guide-lines to diagnosis, which depends on air contrast barium studies, endoscopic recognition of early malignancy, adequate biopsies, and their interpretation. Malignancy was present in an average of 60% of the biopsies taken. The most common type of lesion was IIc. The superficial nature of the malignancy was predicted at endoscopy in four cases but was unsuspected in one case which was considered to be advanced carcinoma until the resected specimen was throughly examined microscopically. The excellent prognosis of EGC was discussed. Only conservative surgery need be performed if the superficial nature of the lesion is recognized before operation.", "contents": "Review of five cases of early gastric carcinoma. Five cases of early gastric carcinoma (EGC) were seen in 12 months. The clinical features did not provide guide-lines to diagnosis, which depends on air contrast barium studies, endoscopic recognition of early malignancy, adequate biopsies, and their interpretation. Malignancy was present in an average of 60% of the biopsies taken. The most common type of lesion was IIc. The superficial nature of the malignancy was predicted at endoscopy in four cases but was unsuspected in one case which was considered to be advanced carcinoma until the resected specimen was throughly examined microscopically. The excellent prognosis of EGC was discussed. Only conservative surgery need be performed if the superficial nature of the lesion is recognized before operation."} {"id": "PMID:1269979", "title": "Effect of vagotomy on the gastric secretory response to intraduodenal osmotic agents in man.", "content": "The effect of intraduodenal infusion of hypertonic saline and glucose on pentagastrin-stimulated gastric secretion was investigated in 35 normal subjects, 32 duodenal ulcer patients and 32 patients after truncal vagotomy and pyloroplasty. A significant gastric inhibitory response occurred after 0.51 M saline and 1-03 M glucose in the normal subjects and duodenal ulcer patients but after vagotomy there was no inhibition. This finding suggests that the inhibitory effect of these agents depends, at least in part, on a vagal reflex in man. The response to very high glucose concentrations persisted after vagotomy and it seems likely that a humoral mechanism may be involved in this situation.", "contents": "Effect of vagotomy on the gastric secretory response to intraduodenal osmotic agents in man. The effect of intraduodenal infusion of hypertonic saline and glucose on pentagastrin-stimulated gastric secretion was investigated in 35 normal subjects, 32 duodenal ulcer patients and 32 patients after truncal vagotomy and pyloroplasty. A significant gastric inhibitory response occurred after 0.51 M saline and 1-03 M glucose in the normal subjects and duodenal ulcer patients but after vagotomy there was no inhibition. This finding suggests that the inhibitory effect of these agents depends, at least in part, on a vagal reflex in man. The response to very high glucose concentrations persisted after vagotomy and it seems likely that a humoral mechanism may be involved in this situation."} {"id": "PMID:1269980", "title": "Effects of aspirin on gastric prostaglandin E (PGE) and acid output in normal subjects.", "content": "Aspirin administration to normal subjects resulted in a reduction in gastric prostaglandin E (PGE) output. Both PGE concentration and gastric juice volume were decreased. Gastric acid output also decreased, although the difference was not statistically significant. An increased sensitivity of the PGE system to inhibition by aspirin at 11 p.m., midnight, and 1am was observed.", "contents": "Effects of aspirin on gastric prostaglandin E (PGE) and acid output in normal subjects. Aspirin administration to normal subjects resulted in a reduction in gastric prostaglandin E (PGE) output. Both PGE concentration and gastric juice volume were decreased. Gastric acid output also decreased, although the difference was not statistically significant. An increased sensitivity of the PGE system to inhibition by aspirin at 11 p.m., midnight, and 1am was observed."} {"id": "PMID:1269981", "title": "Abnormal intestinal bile acid distribution in azotaemic man: a possible role in the pathogenesis of uraemic diarrhoea.", "content": "Proximal intestinal bile acids have been studied in 14 ambulatory patients with varying degrees of azotaemia. When compared with normal subjects, the azotaemic patients showed a significant decrease in deoxycholic acid. Analysis of faecal bile acids of a patient with low intestinal deoxycholic acid also showed low deoxycholic acid with a preponderance of primary bile acids, and contrast with faecal bile acids of a normal subject and a patient with normal intestinal deoxycholic acid. It is suggested that impairment of deconjugation or 7alpha-dehydroxylation might be contributing to the low deoxycholic acid observed in azotaemic patients. Unusual bile acids: ursodeoxycholic acid, 3-hydroxy-7-keto-cholanic acid, and 3,12-dihydroxy-7-keto-cholanic acid were also noted in intestinal aspirates of azotaemic patients. The presence of these bile acids in conjunction with low deoxycholic acid correlates with the symptom of diarrhoea in azotaemic patients, and may contribute to the pathogenesis of diarrhoea in these patients.", "contents": "Abnormal intestinal bile acid distribution in azotaemic man: a possible role in the pathogenesis of uraemic diarrhoea. Proximal intestinal bile acids have been studied in 14 ambulatory patients with varying degrees of azotaemia. When compared with normal subjects, the azotaemic patients showed a significant decrease in deoxycholic acid. Analysis of faecal bile acids of a patient with low intestinal deoxycholic acid also showed low deoxycholic acid with a preponderance of primary bile acids, and contrast with faecal bile acids of a normal subject and a patient with normal intestinal deoxycholic acid. It is suggested that impairment of deconjugation or 7alpha-dehydroxylation might be contributing to the low deoxycholic acid observed in azotaemic patients. Unusual bile acids: ursodeoxycholic acid, 3-hydroxy-7-keto-cholanic acid, and 3,12-dihydroxy-7-keto-cholanic acid were also noted in intestinal aspirates of azotaemic patients. The presence of these bile acids in conjunction with low deoxycholic acid correlates with the symptom of diarrhoea in azotaemic patients, and may contribute to the pathogenesis of diarrhoea in these patients."} {"id": "PMID:1269982", "title": "Limitations of ultracentrifugation and in vivo dialysis as methods of stool analysis.", "content": "Extracellular stool fluid has been sampled by in vivo dialysis, in vitro dialysis, and high speed centrifugation. Detailed comparisons of amino acids and electrolytes have been made between each fluid; normal values and significant differences are summarized. Evidence is provided which suggests that there is release of intracellular contents during normal handling of stool in the laboratory. The amino acids which display the greatest differences between centrifugate and dialysate from given stool specimens are those which are liberated by ultrasonication or aerobic incubation of stool. Factors affecting the chemical stability of stool are discussed. In most circumstances in vivo dialysis would seem to provide the closest approximation to extracellular fluid, providing the faeces remain in the descending colon or rectum for at least two hours.", "contents": "Limitations of ultracentrifugation and in vivo dialysis as methods of stool analysis. Extracellular stool fluid has been sampled by in vivo dialysis, in vitro dialysis, and high speed centrifugation. Detailed comparisons of amino acids and electrolytes have been made between each fluid; normal values and significant differences are summarized. Evidence is provided which suggests that there is release of intracellular contents during normal handling of stool in the laboratory. The amino acids which display the greatest differences between centrifugate and dialysate from given stool specimens are those which are liberated by ultrasonication or aerobic incubation of stool. Factors affecting the chemical stability of stool are discussed. In most circumstances in vivo dialysis would seem to provide the closest approximation to extracellular fluid, providing the faeces remain in the descending colon or rectum for at least two hours."} {"id": "PMID:1269983", "title": "Role of the granuloma in recurrent Crohn's disease.", "content": "The clinical significance of sarcoid-like granulomata in recurrent Crohn's disease has been investigated in 90 patients. The recurrence rate for non-granulomatous disease was double that of granulomatous disease. In granulomatous disease, involvement of the mesenteric lymph nodes did not affect the recurrence rate. This suggests that sarcoid-like granulomata reflect the patients' immune response and support the view that excision of the lymphatic drainage en bloc with affected bowel is not indicated.", "contents": "Role of the granuloma in recurrent Crohn's disease. The clinical significance of sarcoid-like granulomata in recurrent Crohn's disease has been investigated in 90 patients. The recurrence rate for non-granulomatous disease was double that of granulomatous disease. In granulomatous disease, involvement of the mesenteric lymph nodes did not affect the recurrence rate. This suggests that sarcoid-like granulomata reflect the patients' immune response and support the view that excision of the lymphatic drainage en bloc with affected bowel is not indicated."} {"id": "PMID:1269984", "title": "Duodenal ulcers: early and late onset.", "content": "A hospital series of 1042 duodenal ulcer patients was examined to determine the relationship of the age of onset of ulcer dyspepsia with the blood group and with the family history of ulcer dyspepsia. It was found that those patients whose symptoms begin in the first two decades of life (early onset patients) contain a significantly larger proportion of group A, B, and AB subjects and a significantly stronger family history of dyspepsia than those whose symptoms begin from the fourth decade of life onwards (late onset patients), in whom blood group O prevails. The group O status is shown to be associated with a significant proneness to duodenal ulceration and a significant proneness to bleed, and in the late onset patients a significant proneness to bleed recurrently and severely. Bleeding is the predominent complication in the early onset patients. There is a significantly increased tendency for the late onset ulcers to perforate, to become stenosed, to have severe pain, and to be virulent--that is, to be multiple, post-bulbar, or giant. While these features do not appear to be related to the effect of ageing, the occurrence of associated gastric ulceration and the mortality rate was shown to be related.", "contents": "Duodenal ulcers: early and late onset. A hospital series of 1042 duodenal ulcer patients was examined to determine the relationship of the age of onset of ulcer dyspepsia with the blood group and with the family history of ulcer dyspepsia. It was found that those patients whose symptoms begin in the first two decades of life (early onset patients) contain a significantly larger proportion of group A, B, and AB subjects and a significantly stronger family history of dyspepsia than those whose symptoms begin from the fourth decade of life onwards (late onset patients), in whom blood group O prevails. The group O status is shown to be associated with a significant proneness to duodenal ulceration and a significant proneness to bleed, and in the late onset patients a significant proneness to bleed recurrently and severely. Bleeding is the predominent complication in the early onset patients. There is a significantly increased tendency for the late onset ulcers to perforate, to become stenosed, to have severe pain, and to be virulent--that is, to be multiple, post-bulbar, or giant. While these features do not appear to be related to the effect of ageing, the occurrence of associated gastric ulceration and the mortality rate was shown to be related."} {"id": "PMID:1269985", "title": "Simple clinical method of measuring gastric emptying of solid meals.", "content": "The radioisotope techniques used for the measurement of gastric emptying of solid meals in man require complex and expensive scintiscanners of cameras. We have evaluated a simple technique which uses a fixed scintillation detector and compared the results with those obtained from a gamma camera. The rates and patterns of gastric emptying recorded by the two methods correlated well in both healthy volunteers (mean r= 0.95) and patients with duodenal ulcer (mean r =0.89). The scintillation detector provides a reliable and inexpensive method for measurement of gastric emptying of solid meals.", "contents": "Simple clinical method of measuring gastric emptying of solid meals. The radioisotope techniques used for the measurement of gastric emptying of solid meals in man require complex and expensive scintiscanners of cameras. We have evaluated a simple technique which uses a fixed scintillation detector and compared the results with those obtained from a gamma camera. The rates and patterns of gastric emptying recorded by the two methods correlated well in both healthy volunteers (mean r= 0.95) and patients with duodenal ulcer (mean r =0.89). The scintillation detector provides a reliable and inexpensive method for measurement of gastric emptying of solid meals."} {"id": "PMID:1269986", "title": "Course and prognosis of Crohn's disease.", "content": "During the period 1938-70 there were 303 patients at the Radcliffe Infirmary, Oxford, diagnosed as suffering from Crohn's disease. Of these, 82 have been excluded, leaving 221 with a firm diagnosis. These patients have been divided into 'new cases', in which the disease was diagnosed at the Radcliffe Infirmary, and 'referred cases' in which the diagnosis was already made at the time of referral. In this series, there were three main sites of involvement: small intestinal, large intestinal, and both small and large intestinal. Ileocolitis was the commonest anatomical distribution. The disease showed progression to new, sites in a considerable number of the patients during the period under study. There was a fivefold increase of new cases between the first and third decades covered by the study and this applied equally to patients presenting as an acute abdomen, which supports the idea that the disease is truly increasing. Survival curves have been plotted and compared with expected survival curves. In terms of mortality, Crohn's disease emerges as a disease which becomes progressively more dangerous as the years go by, which is in sharp contrast with the findings in ulcerative colitis in which the main risk of dying is in the early years.", "contents": "Course and prognosis of Crohn's disease. During the period 1938-70 there were 303 patients at the Radcliffe Infirmary, Oxford, diagnosed as suffering from Crohn's disease. Of these, 82 have been excluded, leaving 221 with a firm diagnosis. These patients have been divided into 'new cases', in which the disease was diagnosed at the Radcliffe Infirmary, and 'referred cases' in which the diagnosis was already made at the time of referral. In this series, there were three main sites of involvement: small intestinal, large intestinal, and both small and large intestinal. Ileocolitis was the commonest anatomical distribution. The disease showed progression to new, sites in a considerable number of the patients during the period under study. There was a fivefold increase of new cases between the first and third decades covered by the study and this applied equally to patients presenting as an acute abdomen, which supports the idea that the disease is truly increasing. Survival curves have been plotted and compared with expected survival curves. In terms of mortality, Crohn's disease emerges as a disease which becomes progressively more dangerous as the years go by, which is in sharp contrast with the findings in ulcerative colitis in which the main risk of dying is in the early years."} {"id": "PMID:1269987", "title": "Cell mediated immunity to corn starch in starch-induced granulomatous peritonitis.", "content": "Two patients with histologically diagnosed starch induced granulomatous peritonitis (SGP) have been shown to have cell mediated immunity to corn starch using the techniques of macrophage migration inhibition and lymphocyte DNA synthesis. Control groups of normal subjects, patients with uncomplicated laparotomy, and patients with Crohn's disease were negative in both tests. Lymphocytes from two patients with band adhesions, one of whom had biopsy evidence of a granulomatous reaction to starch, were sensitized to starch. Cell mediated immunity to starch may contribute to the pathogenesis of SGP, and some band adhesions may be a chronic low grade manifestation of this disorder.", "contents": "Cell mediated immunity to corn starch in starch-induced granulomatous peritonitis. Two patients with histologically diagnosed starch induced granulomatous peritonitis (SGP) have been shown to have cell mediated immunity to corn starch using the techniques of macrophage migration inhibition and lymphocyte DNA synthesis. Control groups of normal subjects, patients with uncomplicated laparotomy, and patients with Crohn's disease were negative in both tests. Lymphocytes from two patients with band adhesions, one of whom had biopsy evidence of a granulomatous reaction to starch, were sensitized to starch. Cell mediated immunity to starch may contribute to the pathogenesis of SGP, and some band adhesions may be a chronic low grade manifestation of this disorder."} {"id": "PMID:1269988", "title": "Malignant melanoma metastases to the alimentary tract.", "content": "Seven patients are presented each with symptomatic malignant melanoma metastases to the alimentary tract. Where practicable, surgical excision of the metastases is justified because two patients have had worthwhile periods of survival.", "contents": "Malignant melanoma metastases to the alimentary tract. Seven patients are presented each with symptomatic malignant melanoma metastases to the alimentary tract. Where practicable, surgical excision of the metastases is justified because two patients have had worthwhile periods of survival."} {"id": "PMID:1269989", "title": "Measurement of the mean transit time of dietary residue through the human gut.", "content": "A new method is described for measuring the mean transit time (MTT) of digesta through the human gut in which a constant amount of marker (radio-opaque pellets) is fed to subjects with each meal over a period of weeks, and its excretion measured in the stools. The MTT measured by this method (MTT-C) has been compared with MTT measured by giving single doses of similar markers to the same subjects (MTT-S) and with the 80% transit time (80% TT). Mean values on three dietary regimes for the MTT-C (54.2 h +/- 2.5) and MTT-S (54.2 +/- 2.6) were lower than that for 80% TT (63.1 +/- 3.0). The average MTT-C in a group of six healthy young men on an ad libitum diet was 2-3 days (range 0-7-4-0). When additional dietary fibre was added to a standard diet the average MTT-C fell (in all of five subjects) from 2-4 to 1-6 days. A continuous record of MTT-C is obtained by this new method which shows wide variations from week to week even on controlled dietary intakes. Using the single dose technique, evidence is produced which suggests that the MTT-S is a more accurate and reproducible method than the 80% TT.", "contents": "Measurement of the mean transit time of dietary residue through the human gut. A new method is described for measuring the mean transit time (MTT) of digesta through the human gut in which a constant amount of marker (radio-opaque pellets) is fed to subjects with each meal over a period of weeks, and its excretion measured in the stools. The MTT measured by this method (MTT-C) has been compared with MTT measured by giving single doses of similar markers to the same subjects (MTT-S) and with the 80% transit time (80% TT). Mean values on three dietary regimes for the MTT-C (54.2 h +/- 2.5) and MTT-S (54.2 +/- 2.6) were lower than that for 80% TT (63.1 +/- 3.0). The average MTT-C in a group of six healthy young men on an ad libitum diet was 2-3 days (range 0-7-4-0). When additional dietary fibre was added to a standard diet the average MTT-C fell (in all of five subjects) from 2-4 to 1-6 days. A continuous record of MTT-C is obtained by this new method which shows wide variations from week to week even on controlled dietary intakes. Using the single dose technique, evidence is produced which suggests that the MTT-S is a more accurate and reproducible method than the 80% TT."} {"id": "PMID:1269990", "title": "Transit through the gut measured by analysis of a single stool.", "content": "A method is described for measuring transit time through the gut which requires the collection of only one stool. A dose of 20 radio-opaque markers is given to the subject on each of three consecutive days with breakfast, each dose of marker being of a different type. The first stool passed after rising on the fourth day is collected and its marker content analysed. The method has been validated in 15 subjects by comparing it on 36 occasions with mean transit time measured by a continuous marker technique (MTT-C). In 35 of these studies transit measured from a single stool (SST) and MTT-C were significantly correlated R = 0.78 P less than 0.001. In one study the designated stool contained none of the SST markers. An alternative way of validating the SST method is described by comparing it with the average of the three mean transit times from three separate doses of marker (MTT-S). The average MTT-S agreed very closely with MTT-C in 36 studies R = 0.94 P less than 0.001 and proved a satisfactory alternative method for validating transit techniques. In a total of 66 studies in 22 subjects average MTT-S correlated significantly with SST, R = 0.85 P less than 0.001.", "contents": "Transit through the gut measured by analysis of a single stool. A method is described for measuring transit time through the gut which requires the collection of only one stool. A dose of 20 radio-opaque markers is given to the subject on each of three consecutive days with breakfast, each dose of marker being of a different type. The first stool passed after rising on the fourth day is collected and its marker content analysed. The method has been validated in 15 subjects by comparing it on 36 occasions with mean transit time measured by a continuous marker technique (MTT-C). In 35 of these studies transit measured from a single stool (SST) and MTT-C were significantly correlated R = 0.78 P less than 0.001. In one study the designated stool contained none of the SST markers. An alternative way of validating the SST method is described by comparing it with the average of the three mean transit times from three separate doses of marker (MTT-S). The average MTT-S agreed very closely with MTT-C in 36 studies R = 0.94 P less than 0.001 and proved a satisfactory alternative method for validating transit techniques. In a total of 66 studies in 22 subjects average MTT-S correlated significantly with SST, R = 0.85 P less than 0.001."} {"id": "PMID:1269991", "title": "Physiopathology of megarectum: the association of megarectum with encopresis.", "content": "Studies of both rectosphincteric reflex threshold and conscious rectal sensitivity threshold were performed on 15 control subjects and 61 children with a radiological megarectum, 70% of whom were encopretics. In control subjects, the reflex threshold and the sensitivity threshold were obtained with a comparable volume of rectal distension. In the megarectum patients, sensitivity was often considerably reduced, the incidence of encopresis increasing proportionally with the decrease in conscious rectal sensitivity. Patients were segregated in three functional groups, according to measurements of the sensitivity threshold.", "contents": "Physiopathology of megarectum: the association of megarectum with encopresis. Studies of both rectosphincteric reflex threshold and conscious rectal sensitivity threshold were performed on 15 control subjects and 61 children with a radiological megarectum, 70% of whom were encopretics. In control subjects, the reflex threshold and the sensitivity threshold were obtained with a comparable volume of rectal distension. In the megarectum patients, sensitivity was often considerably reduced, the incidence of encopresis increasing proportionally with the decrease in conscious rectal sensitivity. Patients were segregated in three functional groups, according to measurements of the sensitivity threshold."} {"id": "PMID:1269992", "title": "An evaluation of echography in the diagnosis of pancreatic disease.", "content": "In the present study an attempt to evaluate the efficacy of echography as a diagnostic tool has been made. A total of 52 patients (chronic pancreatitis (42); pancreatic cysts (three); and carcinoma of the pancreas (seven)) were studied and the results compared with those from other diagnostic techniques. In 65.7% of chronic pancreatitis patients, and in all cases of carcinoma of the pancreas, echography provided evidence of pancreatic abnormality but in no case could an unambiguous diagnosis of the disease be made. However, in all cases of pancreatic cyst, echography gave precise and unequivocal diagnostic information. There was good agreement between the echographic picture and surgical findings. Cholangiography and duodenography indicated duodenal and choledochal compression in a high proportion of cases in which echography revealed enlargement of the head of the pancreas. It is concluded that echography is a simple, safe, and valuable addition to the techniques available for studying the pancreas.", "contents": "An evaluation of echography in the diagnosis of pancreatic disease. In the present study an attempt to evaluate the efficacy of echography as a diagnostic tool has been made. A total of 52 patients (chronic pancreatitis (42); pancreatic cysts (three); and carcinoma of the pancreas (seven)) were studied and the results compared with those from other diagnostic techniques. In 65.7% of chronic pancreatitis patients, and in all cases of carcinoma of the pancreas, echography provided evidence of pancreatic abnormality but in no case could an unambiguous diagnosis of the disease be made. However, in all cases of pancreatic cyst, echography gave precise and unequivocal diagnostic information. There was good agreement between the echographic picture and surgical findings. Cholangiography and duodenography indicated duodenal and choledochal compression in a high proportion of cases in which echography revealed enlargement of the head of the pancreas. It is concluded that echography is a simple, safe, and valuable addition to the techniques available for studying the pancreas."} {"id": "PMID:1269993", "title": "Endoscopic pancreatography in evaluating results of pancreatico-jejunostomy.", "content": "It has been difficult, employing clinical methods, to establish whether pancreatico-enteric drainage shunts for chronic pancreatitis have remained patent and how the operation has affected the inflammatory changes and ductal pathological morphology. In an attempt objectively to evaluate postoperative results, 13 patients with two different types of pancreatico-jejunostomies were examined with endoscopic pancreatography. Progress of the inflammatory changes was noted to a varying degree in the majority of cases. In four patients subjected to longitudinal split of the pancreatic duct, shunt patency was evidenced. In the remaining nine patients with caudal pancreatico-jejunostomy, no contrast medium could be made to pass the shunts in six cases, whereas passage was clearly demonstrated in one and uncertain in two. All the patients reported clinical improvement after operation.", "contents": "Endoscopic pancreatography in evaluating results of pancreatico-jejunostomy. It has been difficult, employing clinical methods, to establish whether pancreatico-enteric drainage shunts for chronic pancreatitis have remained patent and how the operation has affected the inflammatory changes and ductal pathological morphology. In an attempt objectively to evaluate postoperative results, 13 patients with two different types of pancreatico-jejunostomies were examined with endoscopic pancreatography. Progress of the inflammatory changes was noted to a varying degree in the majority of cases. In four patients subjected to longitudinal split of the pancreatic duct, shunt patency was evidenced. In the remaining nine patients with caudal pancreatico-jejunostomy, no contrast medium could be made to pass the shunts in six cases, whereas passage was clearly demonstrated in one and uncertain in two. All the patients reported clinical improvement after operation."} {"id": "PMID:1269994", "title": "A comparative study of the effect of oral contraceptives and cigarette smoking on platelet adhesiveness.", "content": "The aim of this work was to discover to what extent cigarette smoking and oral contraceptives, either separately or in association, are responsible for platelet adhesiveness changes in humans. Platelet adhesiveness has been measured in 77 subjects, smokers and nonsmokers. 47 of these subjects were women both using and not using oral contraceptives. Cigarette smoking significantly increases platelet adhesiveness both in men and women. On the contrary, if no distinction is made in the smoking habits of female volunteers and they are only divided into two groups according to the use or nonuse of oral contraceptives, no significant change in platelet adhesiveness occurs following intake of oral contraceptives.", "contents": "A comparative study of the effect of oral contraceptives and cigarette smoking on platelet adhesiveness. The aim of this work was to discover to what extent cigarette smoking and oral contraceptives, either separately or in association, are responsible for platelet adhesiveness changes in humans. Platelet adhesiveness has been measured in 77 subjects, smokers and nonsmokers. 47 of these subjects were women both using and not using oral contraceptives. Cigarette smoking significantly increases platelet adhesiveness both in men and women. On the contrary, if no distinction is made in the smoking habits of female volunteers and they are only divided into two groups according to the use or nonuse of oral contraceptives, no significant change in platelet adhesiveness occurs following intake of oral contraceptives."} {"id": "PMID:1269995", "title": "Platelet function after the administration of chlorpromazine to human subjects.", "content": "Chlorpromazine is known to inhibit platelet function in vitro. The intramuscular injection of 50 mg to human volunteers caused only minor changes in platelet function. There was a small, but significant, reduction in the platelet count, the second phase of the double-wave of adenosine diphosphate-induced aggregation and the rate of 5-hydroxytryptamine-induced aggregation. Patients on high doses of chlorpromazine had no demonstrable abnormality of platelet function. This suggests that chlorpromazine, despite its inhibitory effect on platelet function in vitro, is unlikely to interfere with either haemostasis or thrombogenesis after its administration to man.", "contents": "Platelet function after the administration of chlorpromazine to human subjects. Chlorpromazine is known to inhibit platelet function in vitro. The intramuscular injection of 50 mg to human volunteers caused only minor changes in platelet function. There was a small, but significant, reduction in the platelet count, the second phase of the double-wave of adenosine diphosphate-induced aggregation and the rate of 5-hydroxytryptamine-induced aggregation. Patients on high doses of chlorpromazine had no demonstrable abnormality of platelet function. This suggests that chlorpromazine, despite its inhibitory effect on platelet function in vitro, is unlikely to interfere with either haemostasis or thrombogenesis after its administration to man."} {"id": "PMID:1269996", "title": "Interference on the haemostasis in dogs with induced coagulopathies by drugs affecting the platelet function.", "content": "Acetylsalicylic acid and phenylbutazone increased the bleeding significantly from standardized wounds in dogs defibrinogenated with Defibrase. Administration of dipyridamole and Xylocain had no effect. The results were the same in dogs treated with warfarin sodium. The results demonstrate the value of using laboratory animals with an induced coagulopathy when establishing the effect on the haemostasis exerted by drugs known in vitro to interfere with platelet functions. Acetylsalicylic acid and dipyridamole did not alter the activity of the K-vitamin-dependent coagulation factors, factors V, VIII, platelet count or fibrinogen concentration.", "contents": "Interference on the haemostasis in dogs with induced coagulopathies by drugs affecting the platelet function. Acetylsalicylic acid and phenylbutazone increased the bleeding significantly from standardized wounds in dogs defibrinogenated with Defibrase. Administration of dipyridamole and Xylocain had no effect. The results were the same in dogs treated with warfarin sodium. The results demonstrate the value of using laboratory animals with an induced coagulopathy when establishing the effect on the haemostasis exerted by drugs known in vitro to interfere with platelet functions. Acetylsalicylic acid and dipyridamole did not alter the activity of the K-vitamin-dependent coagulation factors, factors V, VIII, platelet count or fibrinogen concentration."} {"id": "PMID:1269997", "title": "Reduced aggregability of platelets in rat anaphylaxis.", "content": "In the PRP of anaphylactic rats, ADP, collagen and thrombin induced platelet aggregation was considerably reduced. Reduced aggregability could be transferred to normal platelets by suspending them in the PPP of anaphylactic animals and the impaired aggregation of platelets from animals undergoing anaphylaxis could be restored by exchanging their plasma for that of normal controls. Ellagic acid, a known activator of factor XII, produced similar alterations as obtained in anaphylactic shcok. It is suggested that the inhibition of platelet aggregation is due to the anaphylactic activation of factor XII and this mechanism may be of importance in rat anaphylaxis.", "contents": "Reduced aggregability of platelets in rat anaphylaxis. In the PRP of anaphylactic rats, ADP, collagen and thrombin induced platelet aggregation was considerably reduced. Reduced aggregability could be transferred to normal platelets by suspending them in the PPP of anaphylactic animals and the impaired aggregation of platelets from animals undergoing anaphylaxis could be restored by exchanging their plasma for that of normal controls. Ellagic acid, a known activator of factor XII, produced similar alterations as obtained in anaphylactic shcok. It is suggested that the inhibition of platelet aggregation is due to the anaphylactic activation of factor XII and this mechanism may be of importance in rat anaphylaxis."} {"id": "PMID:1270025", "title": "Influence of atropine and carbachol on the fluorescence of catecholaminergic structures in selected areas of the rat brain.", "content": "Using the formaldehyde-fluorescence technique, the authors studied the influence of atropine and carbachol, administered intraventricularly to Wistar rats, on the fluorescence of catecholaminergic structures in 20 areas of the CNS, situated within the range of the 10th-46th frontal plane according to KONIG and KLIPPEL. 1. A confirmation of the antagonistic action of atropine and carbachol was obtained. It was expressed by mutually opposed occurrence of the specific fluorescence of the catecholaminergic structures. 2. In 16 out of 20 studied areas of the CNS, carbachol abolished or considerably weakened the specific fluorescence. In 3 areas it was increased by this drug, and one area proved insensitive. 3. Atropine increased the specific fluorescence in the DA (dopaminergic system) areas, while it had varying effects in the NA (noradrenergic system areas. In some areas of the CNS it increased and in others reduced the specific fluorescence of the catecholaminergic structures. 4. An interference between atropine and carbachol is observed, but it seems that the results of the present experiment speak in favour of an interaction between the catecholamine transmitters and ACh in the particular areas of the CNS under the influence of atropine and carbachol. 5. The authors discuss in detail the reactions of the catecholaminergic structures in the particular areas of the CNS, in which, as compared with the control, an increase or a decrease of the specific fluorescence under the influence of the administered drugs was observed.", "contents": "Influence of atropine and carbachol on the fluorescence of catecholaminergic structures in selected areas of the rat brain. Using the formaldehyde-fluorescence technique, the authors studied the influence of atropine and carbachol, administered intraventricularly to Wistar rats, on the fluorescence of catecholaminergic structures in 20 areas of the CNS, situated within the range of the 10th-46th frontal plane according to KONIG and KLIPPEL. 1. A confirmation of the antagonistic action of atropine and carbachol was obtained. It was expressed by mutually opposed occurrence of the specific fluorescence of the catecholaminergic structures. 2. In 16 out of 20 studied areas of the CNS, carbachol abolished or considerably weakened the specific fluorescence. In 3 areas it was increased by this drug, and one area proved insensitive. 3. Atropine increased the specific fluorescence in the DA (dopaminergic system) areas, while it had varying effects in the NA (noradrenergic system areas. In some areas of the CNS it increased and in others reduced the specific fluorescence of the catecholaminergic structures. 4. An interference between atropine and carbachol is observed, but it seems that the results of the present experiment speak in favour of an interaction between the catecholamine transmitters and ACh in the particular areas of the CNS under the influence of atropine and carbachol. 5. The authors discuss in detail the reactions of the catecholaminergic structures in the particular areas of the CNS, in which, as compared with the control, an increase or a decrease of the specific fluorescence under the influence of the administered drugs was observed."} {"id": "PMID:1270026", "title": "Effect of extraction of histones and their reconstitution on [3H] actinomycin D binding to isolated nuclei of the root of Pinus silvestris.", "content": "The purpose of the study presented was to investigate the effect of the extraction of histones on the template activity of DNA, measured by the autoradiographically evaluated intensity of [3H]actinomycin D ([3H]AMD) binding. The study was carried out on nuclei isolated from the root meristem of Pinus silvestris. Histones were removed selectively from them and reconstituted in the nuclei deprived of these proteins. The greatest rise in radioactivity was found after the extraction of the arginine fraction and that of lysine-rich and moderately lysine-rich fractions removed together, whereas the extraction of the lysine-rich fraction does not cause such a considerable increase in radioactivity. The reconstitution of particular histone fractions induced a fall in radioactivity to the level of controls in all the cases examined. No [3H]AMD binding to the nucleolus was found. The extraction of lysine histones results in the decondensation of chromatin and their reconstitution in the formation of complexes of compact chromatin.", "contents": "Effect of extraction of histones and their reconstitution on [3H] actinomycin D binding to isolated nuclei of the root of Pinus silvestris. The purpose of the study presented was to investigate the effect of the extraction of histones on the template activity of DNA, measured by the autoradiographically evaluated intensity of [3H]actinomycin D ([3H]AMD) binding. The study was carried out on nuclei isolated from the root meristem of Pinus silvestris. Histones were removed selectively from them and reconstituted in the nuclei deprived of these proteins. The greatest rise in radioactivity was found after the extraction of the arginine fraction and that of lysine-rich and moderately lysine-rich fractions removed together, whereas the extraction of the lysine-rich fraction does not cause such a considerable increase in radioactivity. The reconstitution of particular histone fractions induced a fall in radioactivity to the level of controls in all the cases examined. No [3H]AMD binding to the nucleolus was found. The extraction of lysine histones results in the decondensation of chromatin and their reconstitution in the formation of complexes of compact chromatin."} {"id": "PMID:1270027", "title": "Radiation-induced histochemical and ultrastructural changes in the enterocytes in the rabbit.", "content": "Ultrastructural changes and enzyme activities in the cell organelles of rabbits were studied within 1, 3, 6, 9, 15 and 30 days of the irradiation with 550 rads of gamma-radiation. Between the 1st and 3rd day after irradiation there was a fall in the succinate dehydrogenase activity in the swollen and frequently tigroidal mitochondria whose number distinctly diminished. By the 15th day these changes disappeared. In the hyaloplasm there was weakening of the reaction for lactate dehydrogenase after 1 day, and an increase in number of polysomes, glycogen granules and smooth vesicles after 3-9 days after irradiation. The glucose-6-phosphatase activity was unchanged and so was the shape of the Golgi apparatus. The activity of lysosomal enzymes and the number of lysosomes in the experimental groups was approximately normal. By the 6th day the activity of alkaline phosphatase in the striated border was lowered, subsequently normal. On the whole, the intensity of postradiation changes in the intestinal mucosal epithelium is correlated with the rhythm of proliferation and shedding of epithelial cells, although some signs of injury persist for longer time periods.", "contents": "Radiation-induced histochemical and ultrastructural changes in the enterocytes in the rabbit. Ultrastructural changes and enzyme activities in the cell organelles of rabbits were studied within 1, 3, 6, 9, 15 and 30 days of the irradiation with 550 rads of gamma-radiation. Between the 1st and 3rd day after irradiation there was a fall in the succinate dehydrogenase activity in the swollen and frequently tigroidal mitochondria whose number distinctly diminished. By the 15th day these changes disappeared. In the hyaloplasm there was weakening of the reaction for lactate dehydrogenase after 1 day, and an increase in number of polysomes, glycogen granules and smooth vesicles after 3-9 days after irradiation. The glucose-6-phosphatase activity was unchanged and so was the shape of the Golgi apparatus. The activity of lysosomal enzymes and the number of lysosomes in the experimental groups was approximately normal. By the 6th day the activity of alkaline phosphatase in the striated border was lowered, subsequently normal. On the whole, the intensity of postradiation changes in the intestinal mucosal epithelium is correlated with the rhythm of proliferation and shedding of epithelial cells, although some signs of injury persist for longer time periods."} {"id": "PMID:1270028", "title": "The activity of alkaline phosphatase in the process of regeneration of rat liver.", "content": "Using GOMORI'S technique, the present authors investigated the dynamics of the alkaline phosphatase activity in the process of liver regeneration after partial hepatectomy. In all 80 rats of the Wistar strain were subjected to experiment, 60 to 75% of the liver parenchyma being removed from each of them. In the course of regeneration a gradual increase in the enzyme activity was observed within the first 48 hours following the operation. This was succeeded by a slow decline of the activity, and after the 25th day after the operation the reaction intensity resembled that recorded for the control animals. It was also ascertained that the fatty degeneration of the liver noted in the initial period of regeneration does not inhibit the activity of alkaline phosphatase.", "contents": "The activity of alkaline phosphatase in the process of regeneration of rat liver. Using GOMORI'S technique, the present authors investigated the dynamics of the alkaline phosphatase activity in the process of liver regeneration after partial hepatectomy. In all 80 rats of the Wistar strain were subjected to experiment, 60 to 75% of the liver parenchyma being removed from each of them. In the course of regeneration a gradual increase in the enzyme activity was observed within the first 48 hours following the operation. This was succeeded by a slow decline of the activity, and after the 25th day after the operation the reaction intensity resembled that recorded for the control animals. It was also ascertained that the fatty degeneration of the liver noted in the initial period of regeneration does not inhibit the activity of alkaline phosphatase."} {"id": "PMID:1270029", "title": "The electron-microscopic picture of postnatal development of oligodendroglia.", "content": "Ultrastructural studies were carried out on the oligodendroglia in the corpus callosum of rat brain in different periods of the animal's extrauterine development. These investigations showed a possibility of distinguishing in the early stages of ontogenesis three forms of oligodendroblasts differing from one another by electron density and the organelle content of the cytoplasm. The beginning of the production of medullary sheaths was noted as early as the first day after birth and the termination of the morphological phase of this process was recorded on the 8th day of postnatal ontogenesis. Moreover, it was found that on the 17th day of the rat's life the process of differentiation of oligodendroglia in the corpus callosum comes to an end.", "contents": "The electron-microscopic picture of postnatal development of oligodendroglia. Ultrastructural studies were carried out on the oligodendroglia in the corpus callosum of rat brain in different periods of the animal's extrauterine development. These investigations showed a possibility of distinguishing in the early stages of ontogenesis three forms of oligodendroblasts differing from one another by electron density and the organelle content of the cytoplasm. The beginning of the production of medullary sheaths was noted as early as the first day after birth and the termination of the morphological phase of this process was recorded on the 8th day of postnatal ontogenesis. Moreover, it was found that on the 17th day of the rat's life the process of differentiation of oligodendroglia in the corpus callosum comes to an end."} {"id": "PMID:1270036", "title": "Treatment of the transsexual and medicolegal issues.", "content": "The carnival, stage or masquerade ball are the only situations where a male is tolerated in assuming the femal role, or vice-versa in Western Society. The transsexual, finding it impossible to maintain his or her self-esteem, is given the opportunity to resolve a profound dilemma via this new medical procedure of six reassignment. Endocrine therapy and conversion surgery raise medicolegal issues illustrative of the difference in perspective between medicine and the law. The nonjudgmental tradition of medicine and the judgmental and prosecuting tradition of law produce attitudes difficult to reconcile in dealing with legal issues that arise in transsexual treatment. This paper deals with the legal ramifications of cross-dressing as part of treatment, transsexual surgery and its exposure to the possibility of legal prosecution, and finally documentary alterations such as birth certificate changes.", "contents": "Treatment of the transsexual and medicolegal issues. The carnival, stage or masquerade ball are the only situations where a male is tolerated in assuming the femal role, or vice-versa in Western Society. The transsexual, finding it impossible to maintain his or her self-esteem, is given the opportunity to resolve a profound dilemma via this new medical procedure of six reassignment. Endocrine therapy and conversion surgery raise medicolegal issues illustrative of the difference in perspective between medicine and the law. The nonjudgmental tradition of medicine and the judgmental and prosecuting tradition of law produce attitudes difficult to reconcile in dealing with legal issues that arise in transsexual treatment. This paper deals with the legal ramifications of cross-dressing as part of treatment, transsexual surgery and its exposure to the possibility of legal prosecution, and finally documentary alterations such as birth certificate changes."} {"id": "PMID:1270038", "title": "Deaths resulting from drugs of abuse.", "content": "This report covers 40 narcotics fatalities from the Northbaden are (Federal Republic of Germany) that came to the Institute of Forensic Medicine, Heidelberg University for autopsy in the years of 1968-1973. Information is given on pathological anatomic and toxicologic findings. A biographical, sociological, psychiatric and criminological catamnesis gave important insight in determinants, motivations, development and course of drug dependence in this area. Basic details are shown and critically evaluated.", "contents": "Deaths resulting from drugs of abuse. This report covers 40 narcotics fatalities from the Northbaden are (Federal Republic of Germany) that came to the Institute of Forensic Medicine, Heidelberg University for autopsy in the years of 1968-1973. Information is given on pathological anatomic and toxicologic findings. A biographical, sociological, psychiatric and criminological catamnesis gave important insight in determinants, motivations, development and course of drug dependence in this area. Basic details are shown and critically evaluated."} {"id": "PMID:1270039", "title": "Polymorphism of A, B and H substances in seminal fluid.", "content": "The polymorphism of A, B and H substances recently described in human saliva has been studied in seminal fluid of 71 subjects. Semen was found to contain the same molecular species of A, B and H substances which were observed in saliva and red cells. The comparison of gel-chromatographic patterns of the saliva and semen of 40 subjects showed identical ABH patterns in 26 cases, while in the remaining 14 some differences were observed.", "contents": "Polymorphism of A, B and H substances in seminal fluid. The polymorphism of A, B and H substances recently described in human saliva has been studied in seminal fluid of 71 subjects. Semen was found to contain the same molecular species of A, B and H substances which were observed in saliva and red cells. The comparison of gel-chromatographic patterns of the saliva and semen of 40 subjects showed identical ABH patterns in 26 cases, while in the remaining 14 some differences were observed."} {"id": "PMID:1270040", "title": "On the significance of posterior crico-arytenoid muscle hemorrhage.", "content": "Sixteen cases of gross fresh PCA muscle hemorrhages were collected from a series of 1500 medicolegal autopsies consecutively performed by the authors, an incidence of about 1%. These hemorrhages occurred in cases of deaths resulting from a variety of causes, including natural disease, physical agents and drugs. In none of the cases was there any evidence of external trauma to the neck. In two cases endotracheal intubation had been performed; however, the lack of injury to the tissues between the tube and the muscles probably rules this factor out. In over 50% of the cases, PCA muscle hemorrhages were found in association with \"asphyxial\" petechial hemorrhages. A consideration of our findings and a study of the literature points out that before considering any individual case of PCA muscle hemorrhages as resulting from direct trauma, additional evidence is needed.", "contents": "On the significance of posterior crico-arytenoid muscle hemorrhage. Sixteen cases of gross fresh PCA muscle hemorrhages were collected from a series of 1500 medicolegal autopsies consecutively performed by the authors, an incidence of about 1%. These hemorrhages occurred in cases of deaths resulting from a variety of causes, including natural disease, physical agents and drugs. In none of the cases was there any evidence of external trauma to the neck. In two cases endotracheal intubation had been performed; however, the lack of injury to the tissues between the tube and the muscles probably rules this factor out. In over 50% of the cases, PCA muscle hemorrhages were found in association with \"asphyxial\" petechial hemorrhages. A consideration of our findings and a study of the literature points out that before considering any individual case of PCA muscle hemorrhages as resulting from direct trauma, additional evidence is needed."} {"id": "PMID:1270045", "title": "[Allergen-specific immunoglobulin E in the serum (RAST), skin tests and mucosa provocation tests using house dust and house mite extract in rhinopathy and bronchial asthma].", "content": "Allergy against house dust and house dust mite was examined by RAST, skin and provocation test, with not identical allergen extracts. 50 patients with allergic rhinitis showed insufficient RAST results with house dust, better results for house dust mite. 65 patients with allergic asthma bronchiale presented satisfying results with house dust, good results with house dust mite. Recommendations are given for the application of RAST in the diagnosis of allergy.", "contents": "[Allergen-specific immunoglobulin E in the serum (RAST), skin tests and mucosa provocation tests using house dust and house mite extract in rhinopathy and bronchial asthma]. Allergy against house dust and house dust mite was examined by RAST, skin and provocation test, with not identical allergen extracts. 50 patients with allergic rhinitis showed insufficient RAST results with house dust, better results for house dust mite. 65 patients with allergic asthma bronchiale presented satisfying results with house dust, good results with house dust mite. Recommendations are given for the application of RAST in the diagnosis of allergy."} {"id": "PMID:1270041", "title": "Forensic odontology in identification of a murder victim in India.", "content": "Absence of 2 left upper incisors and their sockets in the skull of a victim helped to pinpoint identity in a murder case. Age at death of the victim was calculated using Gustafson's method.", "contents": "Forensic odontology in identification of a murder victim in India. Absence of 2 left upper incisors and their sockets in the skull of a victim helped to pinpoint identity in a murder case. Age at death of the victim was calculated using Gustafson's method."} {"id": "PMID:1270042", "title": "Self-inflicted bite marks in battered child syndrome.", "content": "Examination of a child abuse victim revealed bite marks on both arms. These lesions are usually pursued as a clue to the identity of the specific perpetrator. We demonstrated that the bite was from the victim. Importance of this phenomenon in evaluation of bite injuries is discussed.", "contents": "Self-inflicted bite marks in battered child syndrome. Examination of a child abuse victim revealed bite marks on both arms. These lesions are usually pursued as a clue to the identity of the specific perpetrator. We demonstrated that the bite was from the victim. Importance of this phenomenon in evaluation of bite injuries is discussed."} {"id": "PMID:1270046", "title": "[Homotransplantation of the spleen].", "content": "A report of experiences and results on 63 homotransplantations of spleen in dogs is given; 50 of the transplantations were performed in an orthotopic and 13 in a heterotopic way. 10 of the latter had undergone an earlier splenectomy and 3 an earlier orthotopic transplantation, followed by a complete resorption of the first transplant. The course of the transplant was observed by scintigraphy, the function of the anastomosis was controlled by angiography. The immunological and hematological changes were analyzed together with the changes of the protein-electrophoresis and those of the fibrinogenic factors. Scintigraphy has proved to be very useful for the diagnosis of transplant rejection; the measurement of the activity of the lysozyme in the serum compared with the pathoanatomical findings showed a characteristic increase of the activity of the lysozyme during the rejection crisis.", "contents": "[Homotransplantation of the spleen]. A report of experiences and results on 63 homotransplantations of spleen in dogs is given; 50 of the transplantations were performed in an orthotopic and 13 in a heterotopic way. 10 of the latter had undergone an earlier splenectomy and 3 an earlier orthotopic transplantation, followed by a complete resorption of the first transplant. The course of the transplant was observed by scintigraphy, the function of the anastomosis was controlled by angiography. The immunological and hematological changes were analyzed together with the changes of the protein-electrophoresis and those of the fibrinogenic factors. Scintigraphy has proved to be very useful for the diagnosis of transplant rejection; the measurement of the activity of the lysozyme in the serum compared with the pathoanatomical findings showed a characteristic increase of the activity of the lysozyme during the rejection crisis."} {"id": "PMID:1270047", "title": "[Immunology of malignant melanomas].", "content": "The intraperitoneal diffusion-chamber-technique is a closed cell culture system in vivo. Hamster melanoma cells were capable in iso- and heterologous host animals for exponential proliferation. When the host animals had been preimmunized with melanoma cells or hamster lymphocytes a rapid cell lysis was observed in the chambers within 4 hrs after implantation. The cell numbers were reduced about 1-10% of the inoculum. After 6-10 days the cell numbers in chambers from immunized hosts slowly increased in spite of a high level of cytotoxicity in the serum of the animals.", "contents": "[Immunology of malignant melanomas]. The intraperitoneal diffusion-chamber-technique is a closed cell culture system in vivo. Hamster melanoma cells were capable in iso- and heterologous host animals for exponential proliferation. When the host animals had been preimmunized with melanoma cells or hamster lymphocytes a rapid cell lysis was observed in the chambers within 4 hrs after implantation. The cell numbers were reduced about 1-10% of the inoculum. After 6-10 days the cell numbers in chambers from immunized hosts slowly increased in spite of a high level of cytotoxicity in the serum of the animals."} {"id": "PMID:1270060", "title": "Living will does not resolve medical-ethical-legal dilemma.", "content": "The Living Will is an ethically acceptable document that serves to convey a patient's attitude toward terminal illness and to facilitate a physician's decision not to prolong the dying process. But in a Christian context, the Christian Affirmation of Life is a superior document by which to express and aid such decision making. Because the Living Will advances the concept of negative euthanasia--an ethical, legal, and political misnomer--and abets the effort to legalize positive or direct euthanasia, it should not be given legal recognition. As a legal document, the Living Will could seriously affect both patients and physicians.", "contents": "Living will does not resolve medical-ethical-legal dilemma. The Living Will is an ethically acceptable document that serves to convey a patient's attitude toward terminal illness and to facilitate a physician's decision not to prolong the dying process. But in a Christian context, the Christian Affirmation of Life is a superior document by which to express and aid such decision making. Because the Living Will advances the concept of negative euthanasia--an ethical, legal, and political misnomer--and abets the effort to legalize positive or direct euthanasia, it should not be given legal recognition. As a legal document, the Living Will could seriously affect both patients and physicians."} {"id": "PMID:1270063", "title": "Ultrastructure of osteoid osteoma.", "content": "The ultrastructure in five cases of osteoid osteoma is described. The osteoblasts generally had a morphology similar to that of normal osteoblasts with a few differences. They contained irregular indented nuclei, glycogen particles, abundant fine intracytoplasmic fibrils, and rare iron containing lysosomes. In several osteoblasts in two cases there were atypical mitochondria with a lobulated or \"honeycomb\" appearance. These atypical mitochondria were also observed in two osteoclasts; otherwise the cells resembled normal osteoclasts. Other cells present in osteoid osteoma besides osteocytes included osteoprogenitor cells resembling Scott type A and B cells and cells in transitional stages of differentiation. The osteoblasts most likely originated from Scott type A cells of preosteoblasts. The areas of mineralized matrix conformed to the morphology of coarse woven bone. Varying amounts of osteoid were noted. In two cases the osteoid contained, in addition to collagen, fine granular material, which probably represents polysaccharides. No nerve fibers were identified in the material studied. It is thought that osteoid osteoma is a benign neoplastic lesion. A case of osteoblastoma was studied for comparison; the osteoblastoma cells were found to have basically the same morphology as the cells in osteoid osteoma, including the atypical mitochondria. Our ultrastructural observations support the idea that osteoid osteoma and osteoblastoma are closely related lesions.", "contents": "Ultrastructure of osteoid osteoma. The ultrastructure in five cases of osteoid osteoma is described. The osteoblasts generally had a morphology similar to that of normal osteoblasts with a few differences. They contained irregular indented nuclei, glycogen particles, abundant fine intracytoplasmic fibrils, and rare iron containing lysosomes. In several osteoblasts in two cases there were atypical mitochondria with a lobulated or \"honeycomb\" appearance. These atypical mitochondria were also observed in two osteoclasts; otherwise the cells resembled normal osteoclasts. Other cells present in osteoid osteoma besides osteocytes included osteoprogenitor cells resembling Scott type A and B cells and cells in transitional stages of differentiation. The osteoblasts most likely originated from Scott type A cells of preosteoblasts. The areas of mineralized matrix conformed to the morphology of coarse woven bone. Varying amounts of osteoid were noted. In two cases the osteoid contained, in addition to collagen, fine granular material, which probably represents polysaccharides. No nerve fibers were identified in the material studied. It is thought that osteoid osteoma is a benign neoplastic lesion. A case of osteoblastoma was studied for comparison; the osteoblastoma cells were found to have basically the same morphology as the cells in osteoid osteoma, including the atypical mitochondria. Our ultrastructural observations support the idea that osteoid osteoma and osteoblastoma are closely related lesions."} {"id": "PMID:1270064", "title": "Renomedullary interstitial cell lesions and hypertension.", "content": "The notion that renomedullary nodules of the kidney arise as a response to hypertension was tested. Heart weight, ratio of heart weight to body weight, and blood pressure in 160 patients in whom such nodules were found at autopsy were compared with similar measurements in 160 patients without nodules. There were no significant differences between the two groups, and it was concluded that there was no evidence to support the idea that the renomedullary nodule represents a response to hypertension.", "contents": "Renomedullary interstitial cell lesions and hypertension. The notion that renomedullary nodules of the kidney arise as a response to hypertension was tested. Heart weight, ratio of heart weight to body weight, and blood pressure in 160 patients in whom such nodules were found at autopsy were compared with similar measurements in 160 patients without nodules. There were no significant differences between the two groups, and it was concluded that there was no evidence to support the idea that the renomedullary nodule represents a response to hypertension."} {"id": "PMID:1270065", "title": "Malignant hypertension in blacks. Malignant intrarenal arterial disease as observed by light and electron microscopy.", "content": "Volhard and Fahr recognized that hypertensive intrarenal vascular disease could be divided into two groups corresponding to the clinical states of benign and malignant hypertension. Since that time, numerous papers on malignant hypertension, primarily dealing with European derived populations, have emphasized fibrinoid necrosis of small arteries and arterioles as the lesion of malignant hypertension, although some have also recognized a myxoid intimal lesion as characteristic. Today in the United States, however, a significant proportion of malignant hypertension occurs in blacks. In the present study, patients have lacked fibrinoid necrosis of arterioles and only rarely have had some atypical necrosis of small arteries. The prominent, but not pathognomonic, lesion in this series is a myxoid intimal thickening of small arteries consisting of smooth muscle cells, acid mucopolysaccharides, basement membrane-like materal, collagen, and other amorphous and unidentified material, probably plasma derived.", "contents": "Malignant hypertension in blacks. Malignant intrarenal arterial disease as observed by light and electron microscopy. Volhard and Fahr recognized that hypertensive intrarenal vascular disease could be divided into two groups corresponding to the clinical states of benign and malignant hypertension. Since that time, numerous papers on malignant hypertension, primarily dealing with European derived populations, have emphasized fibrinoid necrosis of small arteries and arterioles as the lesion of malignant hypertension, although some have also recognized a myxoid intimal lesion as characteristic. Today in the United States, however, a significant proportion of malignant hypertension occurs in blacks. In the present study, patients have lacked fibrinoid necrosis of arterioles and only rarely have had some atypical necrosis of small arteries. The prominent, but not pathognomonic, lesion in this series is a myxoid intimal thickening of small arteries consisting of smooth muscle cells, acid mucopolysaccharides, basement membrane-like materal, collagen, and other amorphous and unidentified material, probably plasma derived."} {"id": "PMID:1270069", "title": "Frequency of chromosomal fluorescence polymorphism in normal persons and in clinical patients with diagnosed chromosome aberrations.", "content": "By means of a computer program the frequencies of the strongly fluorescent polymorphous chromosomal segments on chromosomes Nos. 3, 4, 13, 14, 15, 21, and 22 among 89 random normal persons and 247 persons suspected of having various chromosome aberrations were determined. It was discovered that: 1. In none of the 13 diagnosis categories are divergencies in frequency of autosomal fluorescence polymorphism, as compared to the normal group, statistically determinable. 2. A worthwhile comparison of the various frequencies of fluorescence polymorphism as recorded by the various investigators in not possible at present, since the applied methods of assessment differ too widely. 3. Standardization of the criteria of assessment and of the nomenclature for the polymorphous chromosomal segment would seem to be a matter of urgent necessity.", "contents": "Frequency of chromosomal fluorescence polymorphism in normal persons and in clinical patients with diagnosed chromosome aberrations. By means of a computer program the frequencies of the strongly fluorescent polymorphous chromosomal segments on chromosomes Nos. 3, 4, 13, 14, 15, 21, and 22 among 89 random normal persons and 247 persons suspected of having various chromosome aberrations were determined. It was discovered that: 1. In none of the 13 diagnosis categories are divergencies in frequency of autosomal fluorescence polymorphism, as compared to the normal group, statistically determinable. 2. A worthwhile comparison of the various frequencies of fluorescence polymorphism as recorded by the various investigators in not possible at present, since the applied methods of assessment differ too widely. 3. Standardization of the criteria of assessment and of the nomenclature for the polymorphous chromosomal segment would seem to be a matter of urgent necessity."} {"id": "PMID:1270070", "title": "Ss blood group associated PAS-staining polymorphism of glycoprotein 3 from human erythrocyte membranes.", "content": "It is shown by discontinuous sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis of human red cell membranes, followed by periodic acid Schiff (PAS) staining and densitometry, that the band PAS-3 (monomeric Ss glycoprotein) exhibits a polymorphism with respect to its staining intensity. In membranes of the genotype SS the staining intensity of this band is about 1.5 times higher than in ss membranes. The experimental error of the method does not permit one to decide, whether membranes of blood type Ss exhibit an intermediate staining intensity or not. The SDS electrophoretic molecular weight of PAS-3 is the same for SS, Ss, or ss membranes. The ratio of PAS to coomassie blue staining intensities, which are a measure of sialic acid and protein content, respectively, are equal for PAS-3 in glycoprotein preparations from SS and ss erythrocytes. These data indicate that the above phenomenon reflects a difference in the glycoprotein content between SS and ss membranes.", "contents": "Ss blood group associated PAS-staining polymorphism of glycoprotein 3 from human erythrocyte membranes. It is shown by discontinuous sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis of human red cell membranes, followed by periodic acid Schiff (PAS) staining and densitometry, that the band PAS-3 (monomeric Ss glycoprotein) exhibits a polymorphism with respect to its staining intensity. In membranes of the genotype SS the staining intensity of this band is about 1.5 times higher than in ss membranes. The experimental error of the method does not permit one to decide, whether membranes of blood type Ss exhibit an intermediate staining intensity or not. The SDS electrophoretic molecular weight of PAS-3 is the same for SS, Ss, or ss membranes. The ratio of PAS to coomassie blue staining intensities, which are a measure of sialic acid and protein content, respectively, are equal for PAS-3 in glycoprotein preparations from SS and ss erythrocytes. These data indicate that the above phenomenon reflects a difference in the glycoprotein content between SS and ss membranes."} {"id": "PMID:1270071", "title": "Partial and complete trisomy 9: delineation of a trisomy 9 syndrome.", "content": "Two infants with trisomy involving chromosome 9 are described. One had complete trisomy 9 and the other karyotype 47,XX,+der(9),t(7;9) (p22;q32)mat. A trisomy 9 syndrome is delineated, consisting of features of the trisomy 9p syndrome and various other malformations. These include abnormalities of the cardiovascular and urogenital systems, cranial suture anomalies, dislocation of the hips and knees and early death. A possible relationship of some of these findings to regions of 9q involved in cases of partial trisomy 9 is suggested.", "contents": "Partial and complete trisomy 9: delineation of a trisomy 9 syndrome. Two infants with trisomy involving chromosome 9 are described. One had complete trisomy 9 and the other karyotype 47,XX,+der(9),t(7;9) (p22;q32)mat. A trisomy 9 syndrome is delineated, consisting of features of the trisomy 9p syndrome and various other malformations. These include abnormalities of the cardiovascular and urogenital systems, cranial suture anomalies, dislocation of the hips and knees and early death. A possible relationship of some of these findings to regions of 9q involved in cases of partial trisomy 9 is suggested."} {"id": "PMID:1270072", "title": "Chromosome measurements on an XXp+ male.", "content": "Measurements carried out on an XX male show that there is a significant difference between the lengths of the short arm of the 2 X chromosomes of this patient and that the short arm of the longer X is also significantly different from that of the X chromosomes derived from normal individuals. The difference lies specifically in the size of the terminal band of the short arm. These results are consistent with the X-Y interchange hypothesis of Ferguson-Smith.", "contents": "Chromosome measurements on an XXp+ male. Measurements carried out on an XX male show that there is a significant difference between the lengths of the short arm of the 2 X chromosomes of this patient and that the short arm of the longer X is also significantly different from that of the X chromosomes derived from normal individuals. The difference lies specifically in the size of the terminal band of the short arm. These results are consistent with the X-Y interchange hypothesis of Ferguson-Smith."} {"id": "PMID:1270073", "title": "Distribution of spontaneous chromosome breaks in human chromosomes.", "content": "Localization of chromosome breaks in human chromosomes was analyzed in 264 peripheral lymphocyte cultures. Three hundred and sixty-nine chromosome breaks could be exactly localized to a chromosome band or region of the Paris Conference nomenclature. The distribution of breaks in the chromosome regions was found to be nonrandom. Chromosome 3 alone had 23% of the breaks and region 3p2 had 13% of the total breaks. Some other chromosome regions, such as 5p1, 9q1, 14q2, and 16q2 also displayed clustering of breaks. Sex chromosomes had less breaks than expected. Spontaneous chromosome breaks were almost exclusively located in the lightly stained G bands.", "contents": "Distribution of spontaneous chromosome breaks in human chromosomes. Localization of chromosome breaks in human chromosomes was analyzed in 264 peripheral lymphocyte cultures. Three hundred and sixty-nine chromosome breaks could be exactly localized to a chromosome band or region of the Paris Conference nomenclature. The distribution of breaks in the chromosome regions was found to be nonrandom. Chromosome 3 alone had 23% of the breaks and region 3p2 had 13% of the total breaks. Some other chromosome regions, such as 5p1, 9q1, 14q2, and 16q2 also displayed clustering of breaks. Sex chromosomes had less breaks than expected. Spontaneous chromosome breaks were almost exclusively located in the lightly stained G bands."} {"id": "PMID:1270074", "title": "Morphologic variability of human chromosomes: polymorphism of constitutive heterochromatin.", "content": "Polymorphism of constitutive heterochromatin has been studied in a series of 30 normal individuals. A high frequency of C-band variants were observed. Twenty-six of the 30 individuals studied had at least one polymorphic variant of the C band. A total of 42 variants were recorded which were predominately localized near the centromeric heterochromatin block of chromosome 9 (26.19%), chromosome 16 (19.05%), and chromosome 1 (16.66%). These results are discussed together with the findings revealed by different studies.", "contents": "Morphologic variability of human chromosomes: polymorphism of constitutive heterochromatin. Polymorphism of constitutive heterochromatin has been studied in a series of 30 normal individuals. A high frequency of C-band variants were observed. Twenty-six of the 30 individuals studied had at least one polymorphic variant of the C band. A total of 42 variants were recorded which were predominately localized near the centromeric heterochromatin block of chromosome 9 (26.19%), chromosome 16 (19.05%), and chromosome 1 (16.66%). These results are discussed together with the findings revealed by different studies."} {"id": "PMID:1270075", "title": "GD (--) Aachen, a new variant of deficient glucose-6-phosphate dehydrogenase. Clinical, genetic, biochemical aspects.", "content": "A deficient G-6PD variant was discovered in 4 males of one family from northwestern Germany. Five generations of this family could be studied. The deficient G-6PD was a new variant, called \"Gd (--) Aachen\". Its main characteristics are the following: severe enzyme deficiency in erythrocytes (3% of normal), contrasting with an almost normal activity in leukocytes; normal molecular specific activity (i.e., normal ratio enzyme activity/cross-reacting material); slow mobility in starch gel electrophoresis (92-94% of normal); increased Michaelis constant for glucoes-6-phosphate (60-70 muM) and NADP+ (20-25 muM); decreased inhibition constant by NADPH with respect to NADP+ (7 muM); increased inhibition by ATP; normal utilization of the substrate analogues; slightly biphasic pH curve; thermal instability, and normal activation energy of the enzymatic reaction. The relationships between the hematologic disorders (severe and frequent hemolytic crises) and the unfavorable kinetic modifications are discussed.", "contents": "GD (--) Aachen, a new variant of deficient glucose-6-phosphate dehydrogenase. Clinical, genetic, biochemical aspects. A deficient G-6PD variant was discovered in 4 males of one family from northwestern Germany. Five generations of this family could be studied. The deficient G-6PD was a new variant, called \"Gd (--) Aachen\". Its main characteristics are the following: severe enzyme deficiency in erythrocytes (3% of normal), contrasting with an almost normal activity in leukocytes; normal molecular specific activity (i.e., normal ratio enzyme activity/cross-reacting material); slow mobility in starch gel electrophoresis (92-94% of normal); increased Michaelis constant for glucoes-6-phosphate (60-70 muM) and NADP+ (20-25 muM); decreased inhibition constant by NADPH with respect to NADP+ (7 muM); increased inhibition by ATP; normal utilization of the substrate analogues; slightly biphasic pH curve; thermal instability, and normal activation energy of the enzymatic reaction. The relationships between the hematologic disorders (severe and frequent hemolytic crises) and the unfavorable kinetic modifications are discussed."} {"id": "PMID:1270076", "title": "The relation of sex, age, smoking status, birth rank and parental ages to pseudocholinesterase activity and phenotypes in a sample of Australian Caucasian adults.", "content": "The frequencies of the pseudocholinesterase alleles E1u, E1a and E1f have been determined in a random sample of Australian residents. The frequency of E1a is the highest yet reported in a large caucasian sample. The considerable variation in E1f frequencies in previously reported samples is discussed in terms of possible sources of error in fluoride number determinations. Enzyme activity was found to increase with age in adulthood and was higher in males than in females. It was also positively correlated with dibucaine number in type U subjects. These observations are in conflict with those reported in previous investigations.", "contents": "The relation of sex, age, smoking status, birth rank and parental ages to pseudocholinesterase activity and phenotypes in a sample of Australian Caucasian adults. The frequencies of the pseudocholinesterase alleles E1u, E1a and E1f have been determined in a random sample of Australian residents. The frequency of E1a is the highest yet reported in a large caucasian sample. The considerable variation in E1f frequencies in previously reported samples is discussed in terms of possible sources of error in fluoride number determinations. Enzyme activity was found to increase with age in adulthood and was higher in males than in females. It was also positively correlated with dibucaine number in type U subjects. These observations are in conflict with those reported in previous investigations."} {"id": "PMID:1270077", "title": "Confirmation of linkage between the loci for HL-A and glyoxalase I.", "content": "Linkage analysis of 7 families with 30 children confirmed previous findings of the linkage between HL-A and GLO. Out of 28 families with 90 children the highest lod score value obtained was + 8.887 (recombination fraction = 0.1).", "contents": "Confirmation of linkage between the loci for HL-A and glyoxalase I. Linkage analysis of 7 families with 30 children confirmed previous findings of the linkage between HL-A and GLO. Out of 28 families with 90 children the highest lod score value obtained was + 8.887 (recombination fraction = 0.1)."} {"id": "PMID:1270078", "title": "Increased sister chromatid exchange events in the human late replicating X.", "content": "Human female blood cultures were labeled with BrdU for detecting sister chromatid exchanges (SCEs) by the Hoechst 33258 fluorescence technique. Late labeling with 3H-thymidine and autoradiography allowed the identification of the late replicating X. The mean number of SCEs in the cells was 13. The isopycnotic X showed an exchange frequency according to its relative length in the karyotype; in the late replicating X a doubled number of SCE events was observed.", "contents": "Increased sister chromatid exchange events in the human late replicating X. Human female blood cultures were labeled with BrdU for detecting sister chromatid exchanges (SCEs) by the Hoechst 33258 fluorescence technique. Late labeling with 3H-thymidine and autoradiography allowed the identification of the late replicating X. The mean number of SCEs in the cells was 13. The isopycnotic X showed an exchange frequency according to its relative length in the karyotype; in the late replicating X a doubled number of SCE events was observed."} {"id": "PMID:1270079", "title": "Cell selection in vivo in normal/aneuploid chromosome abnormalities.", "content": "Cytogenetic follow-up examination has been made of the 9 mixoploid children found among 11 148 newborn children. In 4 of the 9 children there was a significant increase in the frequency of the cell line with normal chromosome constitution and a significant decrease in the normal cell line was found in 1 child. In 4 there was no significant difference from the first to the last examination. The frequency of the cell line with normal chromosomes increased from 32-68% to between 93-97% in 3 cases and to 86% in 1. The possibility that children with mixoploid chromosome abnormalities at birth will reveal no cell line with chromosome abnormality in lymphocyte cultures as adults in spite of having clinical signs of the chromosome aberration found in one cell line at birth is discussed.", "contents": "Cell selection in vivo in normal/aneuploid chromosome abnormalities. Cytogenetic follow-up examination has been made of the 9 mixoploid children found among 11 148 newborn children. In 4 of the 9 children there was a significant increase in the frequency of the cell line with normal chromosome constitution and a significant decrease in the normal cell line was found in 1 child. In 4 there was no significant difference from the first to the last examination. The frequency of the cell line with normal chromosomes increased from 32-68% to between 93-97% in 3 cases and to 86% in 1. The possibility that children with mixoploid chromosome abnormalities at birth will reveal no cell line with chromosome abnormality in lymphocyte cultures as adults in spite of having clinical signs of the chromosome aberration found in one cell line at birth is discussed."} {"id": "PMID:1270080", "title": "Tricho-rhino-phalangeal syndrome. The first case in Japan.", "content": "The case of a 13-year-old girl with tricho-rhino-phalangeal syndrome is presented. It is characterized by sparse and slow growing hair, pear-shaped nose and cone-shaped epiphyses of hands and feet. The inheritance pattern is probably autosomal dominant transmission.", "contents": "Tricho-rhino-phalangeal syndrome. The first case in Japan. The case of a 13-year-old girl with tricho-rhino-phalangeal syndrome is presented. It is characterized by sparse and slow growing hair, pear-shaped nose and cone-shaped epiphyses of hands and feet. The inheritance pattern is probably autosomal dominant transmission."} {"id": "PMID:1270081", "title": "Pathomorphological changes in an early spontaneous abortus with triploidy (69, XXX).", "content": "Triploid (69,XXX) spontaneous abortus with a gestational age of 14--15 weeks (anatomical age of the embryo was 6 weeks) was analyzed macro- and microscopically. There were hydatidiform swelling and cystic degeneration of the villi, without proliferatio of the trophoblast of cells, aplasia of one umbilical artery. The embryo had the following anomalies: cranial and caudal hypoplasia; aplasia of the facial structures (aprosopia), ocular vesicles, nasal stalk, extremity buds, somites, upper jaw, hyoid and pharyngeal arches, esophagus; trachea, Rathke's pouch and oropharyngeal cavity; encephalocele, focal anomalous rudiments of cartilage in the chordamesoderm, atresia of the stomodeal foramen and persistance of the lenticular placode.", "contents": "Pathomorphological changes in an early spontaneous abortus with triploidy (69, XXX). Triploid (69,XXX) spontaneous abortus with a gestational age of 14--15 weeks (anatomical age of the embryo was 6 weeks) was analyzed macro- and microscopically. There were hydatidiform swelling and cystic degeneration of the villi, without proliferatio of the trophoblast of cells, aplasia of one umbilical artery. The embryo had the following anomalies: cranial and caudal hypoplasia; aplasia of the facial structures (aprosopia), ocular vesicles, nasal stalk, extremity buds, somites, upper jaw, hyoid and pharyngeal arches, esophagus; trachea, Rathke's pouch and oropharyngeal cavity; encephalocele, focal anomalous rudiments of cartilage in the chordamesoderm, atresia of the stomodeal foramen and persistance of the lenticular placode."} {"id": "PMID:1270082", "title": "Exomphalos and trisomy 18 syndrome. Report of two cases.", "content": "A large exomphalose was found in two infants with a clinically and cytogenetically typical picture of trisomy 18 syndrome. In addition one infant was a case of male pseudohermaphroditism.", "contents": "Exomphalos and trisomy 18 syndrome. Report of two cases. A large exomphalose was found in two infants with a clinically and cytogenetically typical picture of trisomy 18 syndrome. In addition one infant was a case of male pseudohermaphroditism."} {"id": "PMID:1270083", "title": "[A girl with a deletion (2) (q34q36): cytogenetic and clinical observations (author's transl)].", "content": "We describe a case of (2) (q34;q36) deletion in a girl. The main clinical features of the proband are staturo-ponderal retardation, skull-face dysmorphia and an interauricular communication. The relationship between morphological and chromosomal abnormalities is discussed.", "contents": "[A girl with a deletion (2) (q34q36): cytogenetic and clinical observations (author's transl)]. We describe a case of (2) (q34;q36) deletion in a girl. The main clinical features of the proband are staturo-ponderal retardation, skull-face dysmorphia and an interauricular communication. The relationship between morphological and chromosomal abnormalities is discussed."} {"id": "PMID:1270084", "title": "Lymphocyte nucleoli activation as a marker of autoimmune disorder development. I. Observation in NZB mice.", "content": "An increased number of lymphocytes with nucleoli synthesizing RNA was found in blood and lymph nodes of aged NZB mice who developed an autoimmune disease. This was not observed in young NZB mice and in 40NX mice where no immune disorders were noted.", "contents": "Lymphocyte nucleoli activation as a marker of autoimmune disorder development. I. Observation in NZB mice. An increased number of lymphocytes with nucleoli synthesizing RNA was found in blood and lymph nodes of aged NZB mice who developed an autoimmune disease. This was not observed in young NZB mice and in 40NX mice where no immune disorders were noted."} {"id": "PMID:1270085", "title": "Acquired resistance to ticks. II. Effects of Cyclophosphamide on resistance.", "content": "Guinea-pig developed resistance to Dermacentor andersoni larvae after one infestation. Cyclophosphamide administered in one dose (300 mg/kg) 48 hr prior to an initial infestation with larvae blocked the acquisition of resistance. When cyclophosphamide was given in a similar regimen to guinea-pigs which had already acquired resistance, the expressin of resistance was partially blocked. It was proposed that the blockage of the acquisition of resistance further confirmed the immunological nature of tick resistance. Partial blockage of the expression of resistance by cyclophosphamide substantiated the presence of a humoral component to the resistance mechanism. The presence of a cell-mediated component was previously well established.", "contents": "Acquired resistance to ticks. II. Effects of Cyclophosphamide on resistance. Guinea-pig developed resistance to Dermacentor andersoni larvae after one infestation. Cyclophosphamide administered in one dose (300 mg/kg) 48 hr prior to an initial infestation with larvae blocked the acquisition of resistance. When cyclophosphamide was given in a similar regimen to guinea-pigs which had already acquired resistance, the expressin of resistance was partially blocked. It was proposed that the blockage of the acquisition of resistance further confirmed the immunological nature of tick resistance. Partial blockage of the expression of resistance by cyclophosphamide substantiated the presence of a humoral component to the resistance mechanism. The presence of a cell-mediated component was previously well established."} {"id": "PMID:1270086", "title": "Subfragmentation of the Fc fragment of human IgG1 myeloma protein by thermolysin.", "content": "Human IgG1 Fc fragment was digested at neutral pH by thermolysin, producing two large subfragments: one comprising the major part of the Fc fragment but devoid of the hinge region; the other comprising the Cgamma3 domain. The former fragment retained the capacity to react with \"general\" rheumatoid factors whereas the latter did not, indicating that the binding site for \"general\" rheumatoid factors on the Fc fragment of human IgG1 does not involve the hinge region of the molecule.", "contents": "Subfragmentation of the Fc fragment of human IgG1 myeloma protein by thermolysin. Human IgG1 Fc fragment was digested at neutral pH by thermolysin, producing two large subfragments: one comprising the major part of the Fc fragment but devoid of the hinge region; the other comprising the Cgamma3 domain. The former fragment retained the capacity to react with \"general\" rheumatoid factors whereas the latter did not, indicating that the binding site for \"general\" rheumatoid factors on the Fc fragment of human IgG1 does not involve the hinge region of the molecule."} {"id": "PMID:1270120", "title": "Inhibition of steroid induced gastric ulcers in forestomachectomized albino rats by phenobarbital.", "content": "Oral administration of 2.5 mg of prednisolone/100 gm B.W. to starved forestomachectomized albino rats for three days induces 5-7 acute gastric ulcers with a severity of 3+ in 86% of the rats in the corpus comparable to human gastric ulcers with an ulcer index of 17.1. When 15 mg of Phenobarbital/100 gm B.W. was concomitantly administered with prednisolone either orally or subcutaneously prevents the formation of steroid induced ulcers probably due to their insensitization of gastric epithelium to corticoid ulcerogenic induction. This preliminary observation may have a therapeutic value as this sedative has a common usage. It is is suggested that forestomachectomized rats are best suited for ulcerogenic experiments.", "contents": "Inhibition of steroid induced gastric ulcers in forestomachectomized albino rats by phenobarbital. Oral administration of 2.5 mg of prednisolone/100 gm B.W. to starved forestomachectomized albino rats for three days induces 5-7 acute gastric ulcers with a severity of 3+ in 86% of the rats in the corpus comparable to human gastric ulcers with an ulcer index of 17.1. When 15 mg of Phenobarbital/100 gm B.W. was concomitantly administered with prednisolone either orally or subcutaneously prevents the formation of steroid induced ulcers probably due to their insensitization of gastric epithelium to corticoid ulcerogenic induction. This preliminary observation may have a therapeutic value as this sedative has a common usage. It is is suggested that forestomachectomized rats are best suited for ulcerogenic experiments."} {"id": "PMID:1270121", "title": "A comparative study of a few tests of dynamic lung function.", "content": "A variety of tests like FEV0-76, FEV1, PFR, MEFR is in use for assessment of ventilatory function of the lungs. Each of them has some marginal advantage over the other. It is, therefore, necessary to find out their relative merits and choose the one which can provide the maximum information in a reasonably short time. In this project, a norm of all the above tests for the people of Gujarat of age group 18-20 years has been found, the relative merit of the tests has been discussed and the velocity of air flow at 0.3 sec of expiration has been suggested as the single measurement which may conveniently replace all the other above.", "contents": "A comparative study of a few tests of dynamic lung function. A variety of tests like FEV0-76, FEV1, PFR, MEFR is in use for assessment of ventilatory function of the lungs. Each of them has some marginal advantage over the other. It is, therefore, necessary to find out their relative merits and choose the one which can provide the maximum information in a reasonably short time. In this project, a norm of all the above tests for the people of Gujarat of age group 18-20 years has been found, the relative merit of the tests has been discussed and the velocity of air flow at 0.3 sec of expiration has been suggested as the single measurement which may conveniently replace all the other above."} {"id": "PMID:1270122", "title": "A study of basal metabolic rate in adult Kashmiris.", "content": "Sixty two adults, including forty one males (16-36 yrs.) and twenty one females (16-25 yrs.), were studied by closed circuit method as regards their B.M.R. Males showed a greater lowering of metabolism than the females when compared to MF and AD standards. The females actually showed a higher B.M.R. than the RR standards. Both the sexes had a higher basal metabolism than the value reported from other parts of the country. The difference, however, was significant only in the case of females. Winter metabolism was not sigificantly higher than the summer value in either sex, though females showed some what greater variation.", "contents": "A study of basal metabolic rate in adult Kashmiris. Sixty two adults, including forty one males (16-36 yrs.) and twenty one females (16-25 yrs.), were studied by closed circuit method as regards their B.M.R. Males showed a greater lowering of metabolism than the females when compared to MF and AD standards. The females actually showed a higher B.M.R. than the RR standards. Both the sexes had a higher basal metabolism than the value reported from other parts of the country. The difference, however, was significant only in the case of females. Winter metabolism was not sigificantly higher than the summer value in either sex, though females showed some what greater variation."} {"id": "PMID:1270123", "title": "Mechanism of acti on of chronically administered cannabis extract on the female genital tract of gerbils Meriones hurrianae.", "content": "Daily administration of cannabis extract (2.5 mg/day for a period of 60 days) caused degenerative changes in the ovarian tissue. Luteinization was inhibited. Corpus-luteum degeneration was conspicuous. Distinct effects were produced upon the uterine biochemistry, consisting of decreased RNA, protein, sialic acid and glycogen concentration of the uterus. Vaginal RNA and protein contents were low. An anti-estrogenic action of cannabis extract in female gerbils is suggested.", "contents": "Mechanism of acti on of chronically administered cannabis extract on the female genital tract of gerbils Meriones hurrianae. Daily administration of cannabis extract (2.5 mg/day for a period of 60 days) caused degenerative changes in the ovarian tissue. Luteinization was inhibited. Corpus-luteum degeneration was conspicuous. Distinct effects were produced upon the uterine biochemistry, consisting of decreased RNA, protein, sialic acid and glycogen concentration of the uterus. Vaginal RNA and protein contents were low. An anti-estrogenic action of cannabis extract in female gerbils is suggested."} {"id": "PMID:1270126", "title": "Distinct deoxyribonucleic acid polymerase activities associated with Dane particles and naked Dane cores.", "content": "Two distinct deoxyribonucleic acid polymerase activities were found associated with liver fractions containing Dane particles and Dane cores.", "contents": "Distinct deoxyribonucleic acid polymerase activities associated with Dane particles and naked Dane cores. Two distinct deoxyribonucleic acid polymerase activities were found associated with liver fractions containing Dane particles and Dane cores."} {"id": "PMID:1270124", "title": "The role of imipramine hydrochloride on plasma transaminase and glucose level on rats under altitude stress.", "content": "The effect of exposure of albino rats to simulated high altitude stress of 5000 metres for 3 and 6 hrs on plasma transaminases, non-protein nitrogen (NPN), total protein percentages and blood sugar levels have been studied both with and without the administration of an anti-stress drug Imipramine HCl at 2.0 mg/kg body weight. The drug appears to have a slight hepatotoxic effect.", "contents": "The role of imipramine hydrochloride on plasma transaminase and glucose level on rats under altitude stress. The effect of exposure of albino rats to simulated high altitude stress of 5000 metres for 3 and 6 hrs on plasma transaminases, non-protein nitrogen (NPN), total protein percentages and blood sugar levels have been studied both with and without the administration of an anti-stress drug Imipramine HCl at 2.0 mg/kg body weight. The drug appears to have a slight hepatotoxic effect."} {"id": "PMID:1270127", "title": "Formation of cross-reacting antibodies against cellular and extracellular lipoteichoic acid of Streptococcus mutans BHT.", "content": "Antisera prepared against strains of Streptococcus mutans, particularly strain BHT, contain antibodies to the membrane lipoteichoic acid component that will cross-react with lipoteichoic acids from three species of lactobacilli. A more detailed study of the antibodies to strain BHT confirmed that the antibodies are specific for the polyglycerol phosphate component common to the lipoteichoic acids. Sera with a higher hemagglutinating titer could be obtained by injecting disrupted organisms. The partially purified lipoteichoic acid isolated from the culture fluid of S. mutans BHT was also immunogenic antibodies; antibodies were also formed against another unidentified component in this extracellular fraction.", "contents": "Formation of cross-reacting antibodies against cellular and extracellular lipoteichoic acid of Streptococcus mutans BHT. Antisera prepared against strains of Streptococcus mutans, particularly strain BHT, contain antibodies to the membrane lipoteichoic acid component that will cross-react with lipoteichoic acids from three species of lactobacilli. A more detailed study of the antibodies to strain BHT confirmed that the antibodies are specific for the polyglycerol phosphate component common to the lipoteichoic acids. Sera with a higher hemagglutinating titer could be obtained by injecting disrupted organisms. The partially purified lipoteichoic acid isolated from the culture fluid of S. mutans BHT was also immunogenic antibodies; antibodies were also formed against another unidentified component in this extracellular fraction."} {"id": "PMID:1270125", "title": "Increased fat degradation in the denervated muscle of frog.", "content": "The total lipids triglycerides, free fatty acids, glycerol and acetoaectate levels in the gastrocnemius muscle of frog denervated for 1 month were compared. A significant atrophy without any change in total DNA content per whole muscle was noted on denervation. No significant change in the mitochondrial protein content in the atrophied muscle was noted. Relative to total muscle mass, the total fat, triglyceride, free fatty acids and glycerols decreased on denervation. This suggests the increased degradation of fat during denervation. Concomittantly lypolytic and esterase activities in the atrophied muscle increased. Palmitate and pyruvate oxidations in the mitochondria of atrophied muscle and also the enzymes of beta-oxidative scheme increased. 14C-acetate incorporation rates revealed that there is a decrease in fatty acid synthesis in the atrophied muscle. It was suggested that the increased fatty acid oxidation and decreased fatty acid synthesis in the atrophic process may not be the result of a simple functional demand; but may involve more factors in terms of neuro-muscular functions.", "contents": "Increased fat degradation in the denervated muscle of frog. The total lipids triglycerides, free fatty acids, glycerol and acetoaectate levels in the gastrocnemius muscle of frog denervated for 1 month were compared. A significant atrophy without any change in total DNA content per whole muscle was noted on denervation. No significant change in the mitochondrial protein content in the atrophied muscle was noted. Relative to total muscle mass, the total fat, triglyceride, free fatty acids and glycerols decreased on denervation. This suggests the increased degradation of fat during denervation. Concomittantly lypolytic and esterase activities in the atrophied muscle increased. Palmitate and pyruvate oxidations in the mitochondria of atrophied muscle and also the enzymes of beta-oxidative scheme increased. 14C-acetate incorporation rates revealed that there is a decrease in fatty acid synthesis in the atrophied muscle. It was suggested that the increased fatty acid oxidation and decreased fatty acid synthesis in the atrophic process may not be the result of a simple functional demand; but may involve more factors in terms of neuro-muscular functions."} {"id": "PMID:1270128", "title": "Chemical and biological properties of extracellular slime produced by Staphylococcus aureus grown in high-carbohydrate, high-salt medium.", "content": "Slime material produced by three strains of Staphylococcus aureus grown in the high-carbohydrate, high-salt modified 110 medium contained ribitol teichoic acid and, in two of the three strains, a basic protein reacting with antisera to S. aureus whole cells and cell walls. The basic protein differed chemically and serologically from cell wall mucopeptide and protein A. Substances resembling the capsular antigen of the Smith diffuse strain of S. aureus were not detected, nor were any other uronic acid-containing components. When cell walls, slime material, and teichoic acid were injected intradermally into cows, only cell walls produced a skin reaction.", "contents": "Chemical and biological properties of extracellular slime produced by Staphylococcus aureus grown in high-carbohydrate, high-salt medium. Slime material produced by three strains of Staphylococcus aureus grown in the high-carbohydrate, high-salt modified 110 medium contained ribitol teichoic acid and, in two of the three strains, a basic protein reacting with antisera to S. aureus whole cells and cell walls. The basic protein differed chemically and serologically from cell wall mucopeptide and protein A. Substances resembling the capsular antigen of the Smith diffuse strain of S. aureus were not detected, nor were any other uronic acid-containing components. When cell walls, slime material, and teichoic acid were injected intradermally into cows, only cell walls produced a skin reaction."} {"id": "PMID:1270129", "title": "Subcutaneous multiplication of exfoliatin-producing staphylococci.", "content": "After subcutaneous inoculation of approximately 10(6) cocci, changes in staphylococcal populations were followed by the enumeration of organisms in excised tissues. In contrast to conventionaal Staphylococcus aureus strains, exfoliatin-producing strains were able to multiply in the subcutaneous tissues of neonatal and adult mice. Although strains capable of producing large quantities of exfoliatin were better able to proliferate than strains producing lesser amounts of toxin, it was not determined whether exfoliatin was directly responsible for the observed multiplication. Two variants exhibiting a partial loss in exfoliatin production showed minor changes in proliferative capability. A third strain, after being cured of its exfoliatin plasmid, manifested a marked reduction in exfoliatin production and was unable to multiply subcutaneously. With some strains multiplication proceeded for several hours but was then followed by a decline in the number of viable organisms. Histological sections of subcutaneous lesions revealed a rapid influx of neutrophils, but leukocytes accumulated in the region regardless of whether the organisms multiplied or were eliminated.", "contents": "Subcutaneous multiplication of exfoliatin-producing staphylococci. After subcutaneous inoculation of approximately 10(6) cocci, changes in staphylococcal populations were followed by the enumeration of organisms in excised tissues. In contrast to conventionaal Staphylococcus aureus strains, exfoliatin-producing strains were able to multiply in the subcutaneous tissues of neonatal and adult mice. Although strains capable of producing large quantities of exfoliatin were better able to proliferate than strains producing lesser amounts of toxin, it was not determined whether exfoliatin was directly responsible for the observed multiplication. Two variants exhibiting a partial loss in exfoliatin production showed minor changes in proliferative capability. A third strain, after being cured of its exfoliatin plasmid, manifested a marked reduction in exfoliatin production and was unable to multiply subcutaneously. With some strains multiplication proceeded for several hours but was then followed by a decline in the number of viable organisms. Histological sections of subcutaneous lesions revealed a rapid influx of neutrophils, but leukocytes accumulated in the region regardless of whether the organisms multiplied or were eliminated."} {"id": "PMID:1270130", "title": "Responses of mice immunized with influenza virus by serosol and parenteral routes.", "content": "Antibody levels in sera and respiratory secretions and resistance to respiratory infections were examined in mice given live infuenza virus in small-particle (2 mum) aerosols, large-particle (10 mum) aerosols, intraperitoneally, and subcutaneously. After parenteral administration antibody was found primarily in the serum, but small amounts were recovered in bronchoalveolar washings after 2 to 3 weeks. Specific antibody was present in both sera and bronchoalveolar washings from mice given virus in small-particle aerosols to achieve virus dissemination throughout the respiratory tract. Immunoglobulin A, immunoglobulin G, and trace amounts of immunoglobulin M, all specific for the infecting virus, were detected in bronchoalveolar washings of small-particle aerosol-infected mice. Virus administration in large-particle aerosols (for primary virus localization in upper respiratory tract) at doses greater than those required to initiate infection with small-particle aerosols failed to stimulate production of antibody in sera or bronchoalveolar washings. Small-particle aerosol-immunized mice were resistant to subsequent challenge with 10(2.0) respiratory median lethal doses of virulent virus, whereas large-particle aerosol-immunized mice were not protected. Parenteral immunization modified the course of the disease in challenged mice and reduce mortality rates but did not prevent reinfection of the respiratory tract.", "contents": "Responses of mice immunized with influenza virus by serosol and parenteral routes. Antibody levels in sera and respiratory secretions and resistance to respiratory infections were examined in mice given live infuenza virus in small-particle (2 mum) aerosols, large-particle (10 mum) aerosols, intraperitoneally, and subcutaneously. After parenteral administration antibody was found primarily in the serum, but small amounts were recovered in bronchoalveolar washings after 2 to 3 weeks. Specific antibody was present in both sera and bronchoalveolar washings from mice given virus in small-particle aerosols to achieve virus dissemination throughout the respiratory tract. Immunoglobulin A, immunoglobulin G, and trace amounts of immunoglobulin M, all specific for the infecting virus, were detected in bronchoalveolar washings of small-particle aerosol-infected mice. Virus administration in large-particle aerosols (for primary virus localization in upper respiratory tract) at doses greater than those required to initiate infection with small-particle aerosols failed to stimulate production of antibody in sera or bronchoalveolar washings. Small-particle aerosol-immunized mice were resistant to subsequent challenge with 10(2.0) respiratory median lethal doses of virulent virus, whereas large-particle aerosol-immunized mice were not protected. Parenteral immunization modified the course of the disease in challenged mice and reduce mortality rates but did not prevent reinfection of the respiratory tract."} {"id": "PMID:1270131", "title": "Synergistic protective effect in rabbits of immunization with Vibrio cholerae lipopolysaccharide and toxin/toxoid.", "content": "Subcutaneous immunization of rabbits with a combination of Vibrio cholerae lipopolysaccharide (LPS) and enterotoxin induced a more than 100-fold-higher degree of protection against intestinal challenge with live cholera vibrios than did vaccination with either of the two antigens alone. Such a synergistic effect was also obtained by immunization with a combination of LPS and choleragenoid. The immunization with LPS and toxin (or toxoid) in combination did not enhance the reistance to toxin challenge above that induced by the toxin component alone. This, together with data from titrations of anti-LPS and antitoxin antibodies in serum and in intestinal washings, contradicts enhanced immune responses due to adjuvant action of the two antigens as the explanation for the synergistic effect of the combined vaccines. A more likely explanation would be that the antibacterial and antitoxic immune responses, without being increased in themselves, function synergistically by interfering with two separate events in cholera pathogensis.", "contents": "Synergistic protective effect in rabbits of immunization with Vibrio cholerae lipopolysaccharide and toxin/toxoid. Subcutaneous immunization of rabbits with a combination of Vibrio cholerae lipopolysaccharide (LPS) and enterotoxin induced a more than 100-fold-higher degree of protection against intestinal challenge with live cholera vibrios than did vaccination with either of the two antigens alone. Such a synergistic effect was also obtained by immunization with a combination of LPS and choleragenoid. The immunization with LPS and toxin (or toxoid) in combination did not enhance the reistance to toxin challenge above that induced by the toxin component alone. This, together with data from titrations of anti-LPS and antitoxin antibodies in serum and in intestinal washings, contradicts enhanced immune responses due to adjuvant action of the two antigens as the explanation for the synergistic effect of the combined vaccines. A more likely explanation would be that the antibacterial and antitoxic immune responses, without being increased in themselves, function synergistically by interfering with two separate events in cholera pathogensis."} {"id": "PMID:1270132", "title": "Preparative isotachophoretic separation of skin test antigens from blastomycin purified derivative.", "content": "This investigation examined the theoretical and practical parameters requisite to preparatory istachophoretic separation of blastomycin purified derivative. It resulted in a relatively simple, two-step procedure for preparation of blastomycin antigens in milligram quantitites that exhibited sensitivity and specificity in experimentally infected guinea pigs. Analysis of the nine isotachophoretic fractions for skin test sensitivity and specificity provided some insight into the generally accepted unreliability of blastomycin when used for immunological evaluation.", "contents": "Preparative isotachophoretic separation of skin test antigens from blastomycin purified derivative. This investigation examined the theoretical and practical parameters requisite to preparatory istachophoretic separation of blastomycin purified derivative. It resulted in a relatively simple, two-step procedure for preparation of blastomycin antigens in milligram quantitites that exhibited sensitivity and specificity in experimentally infected guinea pigs. Analysis of the nine isotachophoretic fractions for skin test sensitivity and specificity provided some insight into the generally accepted unreliability of blastomycin when used for immunological evaluation."} {"id": "PMID:1270133", "title": "Effective immunity to dental caries: protection of malnourished rats by local injection of Streptococcus mutans.", "content": "When rats from dams fed a low-protein diet were injected with whole, killed Strepococcus mutans 6715 cells in the region of the submandibular gland, they developed serum and salivary agglutinins to this microorganism. Titers of agglutinins in malnourished rats were similar to those observed in rats from dams fed a nutritionally adequate diet that were locally injected with S. mutans. Furthermore, both groups of immunized rats subsequently infected with cariogenic S. mutans 6715 had lower mean caries scores than infected, nonimmunized rats. This reduced incidence of caries scores than infected, nonimmunized rats. This reduced incidence of caries was evident on all molar surfaces. The mean body weights of immunized and nonimmunized, protein-deficient rats were not significantly different; likewise, both immunized and nonimmunize normally nourished rats exhibited similar weight gains. Malnourished rats, not immunized but infected with S. mutans, had significantly more caries than normal, nonimmunized infected rats. Both dietary groups of noninfected rats had very few carious lesions. These results suggest that carious lesions observed in these rats resulted from S. mutans 6715 infection. Furthermore, protein-malnourished rats, injected in the region of the submandibular gland with whole, killed S. mutans elicit an immune response and are protected against S. mutans-induced caries.", "contents": "Effective immunity to dental caries: protection of malnourished rats by local injection of Streptococcus mutans. When rats from dams fed a low-protein diet were injected with whole, killed Strepococcus mutans 6715 cells in the region of the submandibular gland, they developed serum and salivary agglutinins to this microorganism. Titers of agglutinins in malnourished rats were similar to those observed in rats from dams fed a nutritionally adequate diet that were locally injected with S. mutans. Furthermore, both groups of immunized rats subsequently infected with cariogenic S. mutans 6715 had lower mean caries scores than infected, nonimmunized rats. This reduced incidence of caries scores than infected, nonimmunized rats. This reduced incidence of caries was evident on all molar surfaces. The mean body weights of immunized and nonimmunized, protein-deficient rats were not significantly different; likewise, both immunized and nonimmunize normally nourished rats exhibited similar weight gains. Malnourished rats, not immunized but infected with S. mutans, had significantly more caries than normal, nonimmunized infected rats. Both dietary groups of noninfected rats had very few carious lesions. These results suggest that carious lesions observed in these rats resulted from S. mutans 6715 infection. Furthermore, protein-malnourished rats, injected in the region of the submandibular gland with whole, killed S. mutans elicit an immune response and are protected against S. mutans-induced caries."} {"id": "PMID:1270134", "title": "Aerosol vaccination of mice with a live, temperature- sensitive recombinant influenza virus.", "content": "Mice were vaccinated intranasally (i.n.) or with small-particle aerosols (SPA; 2 mum) or large-particle aerosols (LPA; 8 mum) of an attenuated, temperature-sensitive, recombinant A influenza (H3N2) virus, ts-1 (E). Serum virus-neutralizing and hemagglutination inhibition antibodies were detected for all vaccinated mice by 28 days. Bronchoalveolar wash fluids had increased levels of immunoglobulin (IgG, IgA) only in the i.n. -vaccinated mice. Hemagglutination and virus-neutralizing antibodies were detected in the SPA- and i.n. -vaccinated groups but not in the LPA vaccinates. Upon challenge with SPA of a mouse virulent H3N2 influenza vitus, total protection was obtained for the SPA- and I.N. -vaccinated mice, whereas only 89% of the LPA group survived. Replication of the challenge virus was signifcantly repressed in both the lower and upper respiratory tracts of the three groups of vaccinated mice compared to the nonvaccinated controls. The protection afforded the SPA- and i.n. -vaccinated mice was the same as measured for mice after recovery from earlier subelthal active infection with virulent virus.", "contents": "Aerosol vaccination of mice with a live, temperature- sensitive recombinant influenza virus. Mice were vaccinated intranasally (i.n.) or with small-particle aerosols (SPA; 2 mum) or large-particle aerosols (LPA; 8 mum) of an attenuated, temperature-sensitive, recombinant A influenza (H3N2) virus, ts-1 (E). Serum virus-neutralizing and hemagglutination inhibition antibodies were detected for all vaccinated mice by 28 days. Bronchoalveolar wash fluids had increased levels of immunoglobulin (IgG, IgA) only in the i.n. -vaccinated mice. Hemagglutination and virus-neutralizing antibodies were detected in the SPA- and i.n. -vaccinated groups but not in the LPA vaccinates. Upon challenge with SPA of a mouse virulent H3N2 influenza vitus, total protection was obtained for the SPA- and I.N. -vaccinated mice, whereas only 89% of the LPA group survived. Replication of the challenge virus was signifcantly repressed in both the lower and upper respiratory tracts of the three groups of vaccinated mice compared to the nonvaccinated controls. The protection afforded the SPA- and i.n. -vaccinated mice was the same as measured for mice after recovery from earlier subelthal active infection with virulent virus."} {"id": "PMID:1270135", "title": "Host defenses in experimental scrub typhus: histopathological correlates.", "content": "Intraperitoneal (i.p.) infection of BALB/c mice with 1,000 50% mouse lethal doses of the Karp strain of Rickettsia tsutsugamushi was inevitably lethal, and associated pathological alterations were confined to the peritoneal cavity. These included: (i) continuous proliferation of rickettsial organisms in peritoneal macrophages until death; (ii) hepatic granulomas appearing 6 days after infection and increasing in size and number until death; (iii) splenomegaly, resulting principally from proliferation of lymphoid tissue, and (iv) terminal peritonitis. Under two circumstances, i.p. infections with R. tsutsugamushi were not lethal: (i) infection with 100 50% mouse infectious doses of the Gilliam strain, which, in fact, resulted in immune protection against otherwise lethal Karp challenge; and (ii) Karp infection of animals immunized with the Gilliam strain. In both cases, the associated pathological abnormalities were, as with primary Karp infection, restricted to the peritoneal cavity. Also similar was the striking splenomegaly due to lymphoid proliferation, which was particularly prominent in immunized animals. In contrast to primary and lethal Karp infection, however, these infections were characterized by: (i) minimal and transient proliferation of rickettsial organisms in peritoneal macrophages; (ii) disappearance of hepatic granulomas; and (iii) absence of peritonitis. It was concluded that the survival of an animal bearing an i.p. infection of scrub typhus depended on its ability to concentrate a sufficiently vigorous immune response in the peritoneal cavity, resulting in the evolution of rickettsiacidal macrophages capable of suppressing the infection.", "contents": "Host defenses in experimental scrub typhus: histopathological correlates. Intraperitoneal (i.p.) infection of BALB/c mice with 1,000 50% mouse lethal doses of the Karp strain of Rickettsia tsutsugamushi was inevitably lethal, and associated pathological alterations were confined to the peritoneal cavity. These included: (i) continuous proliferation of rickettsial organisms in peritoneal macrophages until death; (ii) hepatic granulomas appearing 6 days after infection and increasing in size and number until death; (iii) splenomegaly, resulting principally from proliferation of lymphoid tissue, and (iv) terminal peritonitis. Under two circumstances, i.p. infections with R. tsutsugamushi were not lethal: (i) infection with 100 50% mouse infectious doses of the Gilliam strain, which, in fact, resulted in immune protection against otherwise lethal Karp challenge; and (ii) Karp infection of animals immunized with the Gilliam strain. In both cases, the associated pathological abnormalities were, as with primary Karp infection, restricted to the peritoneal cavity. Also similar was the striking splenomegaly due to lymphoid proliferation, which was particularly prominent in immunized animals. In contrast to primary and lethal Karp infection, however, these infections were characterized by: (i) minimal and transient proliferation of rickettsial organisms in peritoneal macrophages; (ii) disappearance of hepatic granulomas; and (iii) absence of peritonitis. It was concluded that the survival of an animal bearing an i.p. infection of scrub typhus depended on its ability to concentrate a sufficiently vigorous immune response in the peritoneal cavity, resulting in the evolution of rickettsiacidal macrophages capable of suppressing the infection."} {"id": "PMID:1270136", "title": "Cytotoxic effect of the thermostable direct hemolysin produced by Vibrio parahaemolyticus on FL cells.", "content": "The thermostable direct hemolysin produced by Vibrio parahaemolyticus showed cytotoxic activity on FL cells derived from human amniotic membrane. Scanning electron micrographs of the whole cells showed that the microvilli on the cell surface decreased in number and changed in shape on treatment with the hemolysin. Most of the microvilli disappeared before death of the cells, as judged from the results of staining the cells with trypan blue and measuring release of alkaline phosphatase from the cells. Electron micrographs of thin sections ofthe cells showed that the cytoplasm of the cells was not significantly affected by treatment with sublethal amounts of hemolysin, even when the microvilli on the cell surface were significantly affected. Lethal amounts of hemolysin affected the cytoplasm and caused disarovilli on the cell surface are affected by treatment with the hemolysin before cytoxic effects develop.", "contents": "Cytotoxic effect of the thermostable direct hemolysin produced by Vibrio parahaemolyticus on FL cells. The thermostable direct hemolysin produced by Vibrio parahaemolyticus showed cytotoxic activity on FL cells derived from human amniotic membrane. Scanning electron micrographs of the whole cells showed that the microvilli on the cell surface decreased in number and changed in shape on treatment with the hemolysin. Most of the microvilli disappeared before death of the cells, as judged from the results of staining the cells with trypan blue and measuring release of alkaline phosphatase from the cells. Electron micrographs of thin sections ofthe cells showed that the cytoplasm of the cells was not significantly affected by treatment with sublethal amounts of hemolysin, even when the microvilli on the cell surface were significantly affected. Lethal amounts of hemolysin affected the cytoplasm and caused disarovilli on the cell surface are affected by treatment with the hemolysin before cytoxic effects develop."} {"id": "PMID:1270137", "title": "Growth and effects of ureaplasmas (T mycoplasmas) in bovine oviductal organ cultures.", "content": "Ureaplasmas isolated from the human genital tract and from the genital and respiratory tracts of cattle were grown in association with organ cultures of bovine oviduct (uterine tube). All strains of unreaplasmas multiplied in organ cultures, stopped ciliary activity, and caused histological lesions. Most strains grew well, and 10(8) to 10(9) color-changing units were determined 18 to 144 h after inoculation. Twenty-four to 144 h after inoculation with unreaplasmas, ciliostasis was complete. Ciliostasis was also caused by additions of nonviable cultures at pH 8.8 (or adjusted to 7.4) or washed disrupted cells (100 mug of protein/ml); it occurred in 48 to 96 h. The cilia-stopping effect of nonviable cultures was diminished by heating (56 C for 30 min) and was abolished by boiling. When added to fresh medium in amounts exceeding 25%, nonviable unreaplasmal cultures completely inhibited ureaplasmal growth. By light, scanning, and transmission electron microscopy, cilia-stopping effect was correlated with collapse and sloughing of the cilia (the initial lesion was \"bent\" cilia), with bulging and vacuolization of secretory and ciliated cells, and finally with disorganization of the epithelium, necrosis, and desquamation.", "contents": "Growth and effects of ureaplasmas (T mycoplasmas) in bovine oviductal organ cultures. Ureaplasmas isolated from the human genital tract and from the genital and respiratory tracts of cattle were grown in association with organ cultures of bovine oviduct (uterine tube). All strains of unreaplasmas multiplied in organ cultures, stopped ciliary activity, and caused histological lesions. Most strains grew well, and 10(8) to 10(9) color-changing units were determined 18 to 144 h after inoculation. Twenty-four to 144 h after inoculation with unreaplasmas, ciliostasis was complete. Ciliostasis was also caused by additions of nonviable cultures at pH 8.8 (or adjusted to 7.4) or washed disrupted cells (100 mug of protein/ml); it occurred in 48 to 96 h. The cilia-stopping effect of nonviable cultures was diminished by heating (56 C for 30 min) and was abolished by boiling. When added to fresh medium in amounts exceeding 25%, nonviable unreaplasmal cultures completely inhibited ureaplasmal growth. By light, scanning, and transmission electron microscopy, cilia-stopping effect was correlated with collapse and sloughing of the cilia (the initial lesion was \"bent\" cilia), with bulging and vacuolization of secretory and ciliated cells, and finally with disorganization of the epithelium, necrosis, and desquamation."} {"id": "PMID:1270138", "title": "Unbalanced growth and macromolecular synthesis in Streptococcus mutans FA-1.", "content": "The continued synthesis of deoxyribonucleic acid, protein, cell wall peptidoglycan and intracellular iodophilic polysaccharide (IPS) by Streptococcus mutans strain FA-1 after several treatments intended to inhibit protein synthesis was studied. Exponential-phase cultures were: (i) simultaneously deprived of two required amino acids (cystine and leucine) that are not present in the cell wall peptidoglycan of this species; (ii) depreived of required amino acids (lysine or glutamate plus glutamine ) that are present in both peptidoglycan and protein; or (iii) treated with tetracycline. Each of these three types of treatment was accompanied by a different pattern of unbalanced growth. The patterns of unbalanced growth that accompanied treatments (i) or (ii) differed substantially from the patterns observed previously for Streptococcus faecalis ATCC 9790, a noncariogenic organism that does not contain IPS. In contrast to S. faecalis 9790, S. mutans FA-1 failed to accumulate peptidoglycan and thicken its wall when deprived of non-wall amino acids. Instead, S. mutans FA-1 continued to accumulate IPS to levels substantially higher than those found in exponential-phase cells. Again, in contrast to S. faecalis, S. mutans FA-1 failed to autolyze upon deprivation of essential precursors of wall peptidoglycan. Under conditions of lysine of glutamate/glutamine deprivation, S. mutans FA-1 continued to accumulate IPS to very high levels. Treatment with tetracycline did result in peptidoglycan accumulation and wall thickening in a manner very similar to that observed previously for inhibition of protein synthesis in S. faecalis. Realtively little IPS synthesis continued after tetracycline treatment. Accumulation of IPS appeared to occur when both ribonucleic acid and peptidoglycan synthesis were severely inhibited. The observations are discussed in terms of the survival of cariogenic organisms in the oral environment.", "contents": "Unbalanced growth and macromolecular synthesis in Streptococcus mutans FA-1. The continued synthesis of deoxyribonucleic acid, protein, cell wall peptidoglycan and intracellular iodophilic polysaccharide (IPS) by Streptococcus mutans strain FA-1 after several treatments intended to inhibit protein synthesis was studied. Exponential-phase cultures were: (i) simultaneously deprived of two required amino acids (cystine and leucine) that are not present in the cell wall peptidoglycan of this species; (ii) depreived of required amino acids (lysine or glutamate plus glutamine ) that are present in both peptidoglycan and protein; or (iii) treated with tetracycline. Each of these three types of treatment was accompanied by a different pattern of unbalanced growth. The patterns of unbalanced growth that accompanied treatments (i) or (ii) differed substantially from the patterns observed previously for Streptococcus faecalis ATCC 9790, a noncariogenic organism that does not contain IPS. In contrast to S. faecalis 9790, S. mutans FA-1 failed to accumulate peptidoglycan and thicken its wall when deprived of non-wall amino acids. Instead, S. mutans FA-1 continued to accumulate IPS to levels substantially higher than those found in exponential-phase cells. Again, in contrast to S. faecalis, S. mutans FA-1 failed to autolyze upon deprivation of essential precursors of wall peptidoglycan. Under conditions of lysine of glutamate/glutamine deprivation, S. mutans FA-1 continued to accumulate IPS to very high levels. Treatment with tetracycline did result in peptidoglycan accumulation and wall thickening in a manner very similar to that observed previously for inhibition of protein synthesis in S. faecalis. Realtively little IPS synthesis continued after tetracycline treatment. Accumulation of IPS appeared to occur when both ribonucleic acid and peptidoglycan synthesis were severely inhibited. The observations are discussed in terms of the survival of cariogenic organisms in the oral environment."} {"id": "PMID:1270139", "title": "Lymphocytic choriomeningitis virus infection in fetal, newborn, and young adult Syrian hamsters (Mesocricetus auratus).", "content": "The pathogenesis of lymphocytic choriomeningitis virus infection in fetal, newborn, and young adult hamsters was studied. Infected newborn hamsters initially developed a persistent viremia and viruria with titers often in excess of 10(4.0) mean infectious doses/0.03 ml of blood or urine. After week 12 two different patterns of infection became evident. Approximately one-half of the hamsters eventually cleared the infection, whereas the others developed a chronic progressive and ultimalely fatal disease characterized by continuous high-titered viremia and viruria and high titers of virus in their tissues. Complement-fixing antibody and, to a lesser degree, virus-neutralizing antibody coexisted with the viremia. Hamsters with persistently high levels of viremia and viruria developed chronic glomerulonephritis and widespread vasculitis, whereas hamsters that cleared their infections did not develop these lesions. Litters of hamsters born to viremic mothers were invariably infected. Litter sizes were small and breeding effectiveness was reduce; however, vertical, congenital infection was successfully passed through three generations. The course of infection in the congenitally infected hamsters was similar to that in newborn infected hamsters, with all animals producing complement-fixing antibody, some animals being capable of clearing the viremia and remaining healthy, and other animals having persistent viremia and fatal disease. Inoculated young adult hamsters did not become diseased, developed viremia and viruria which persisted up to 3 and 6 months, respectively, and developed complement-fixing antibody by 10 days after infection. The prolonged urinary excretion of large amounts of lymphocytic choriomeningitis virus by asymptomatic, chronically infected hamsters is an important public health consideration when dealing with potential human infection.", "contents": "Lymphocytic choriomeningitis virus infection in fetal, newborn, and young adult Syrian hamsters (Mesocricetus auratus). The pathogenesis of lymphocytic choriomeningitis virus infection in fetal, newborn, and young adult hamsters was studied. Infected newborn hamsters initially developed a persistent viremia and viruria with titers often in excess of 10(4.0) mean infectious doses/0.03 ml of blood or urine. After week 12 two different patterns of infection became evident. Approximately one-half of the hamsters eventually cleared the infection, whereas the others developed a chronic progressive and ultimalely fatal disease characterized by continuous high-titered viremia and viruria and high titers of virus in their tissues. Complement-fixing antibody and, to a lesser degree, virus-neutralizing antibody coexisted with the viremia. Hamsters with persistently high levels of viremia and viruria developed chronic glomerulonephritis and widespread vasculitis, whereas hamsters that cleared their infections did not develop these lesions. Litters of hamsters born to viremic mothers were invariably infected. Litter sizes were small and breeding effectiveness was reduce; however, vertical, congenital infection was successfully passed through three generations. The course of infection in the congenitally infected hamsters was similar to that in newborn infected hamsters, with all animals producing complement-fixing antibody, some animals being capable of clearing the viremia and remaining healthy, and other animals having persistent viremia and fatal disease. Inoculated young adult hamsters did not become diseased, developed viremia and viruria which persisted up to 3 and 6 months, respectively, and developed complement-fixing antibody by 10 days after infection. The prolonged urinary excretion of large amounts of lymphocytic choriomeningitis virus by asymptomatic, chronically infected hamsters is an important public health consideration when dealing with potential human infection."} {"id": "PMID:1270140", "title": "Purification of staphylococcal alpha-toxin by adsorption chromatography on glass.", "content": "Staphylococcal alpha-toxin was purified from Staphylococcus aureus growth medium using adsorption chromatography on controlled pore glass beads. Elution of alpha-toxin from the unmodified glass surface of the beads with various anions generally followed the chaotropic series. Alpha-toxin, purified by glass bead chromatography, is composed of a single electrophoretic form, containing less than 2% of other forms.", "contents": "Purification of staphylococcal alpha-toxin by adsorption chromatography on glass. Staphylococcal alpha-toxin was purified from Staphylococcus aureus growth medium using adsorption chromatography on controlled pore glass beads. Elution of alpha-toxin from the unmodified glass surface of the beads with various anions generally followed the chaotropic series. Alpha-toxin, purified by glass bead chromatography, is composed of a single electrophoretic form, containing less than 2% of other forms."} {"id": "PMID:1270141", "title": "Inhibition of lethality in endotoxin-challenged mice treated with zinc chloride.", "content": "Zinc chloride protected against lethality in mice undergoing endotoxin shock.", "contents": "Inhibition of lethality in endotoxin-challenged mice treated with zinc chloride. Zinc chloride protected against lethality in mice undergoing endotoxin shock."} {"id": "PMID:1270142", "title": "Solid-phase radioimmunoassay for antibodies to flavivirus structural and nonstructural proteins.", "content": "A micro-solid-phase radioimmunoassay (SPRIA) is described for quantitation of antibodies to purified flaviviruses as well as to the purified envelope glycoprotein and 80,000-molecular-weight viral nonstructural protein. Sera from mice experimentally infected with Saint Louis encephalitis (SLE) virus or from humans after a primary SLE virus infection reacted more specifically with the major viral envelope protein in the SPRIA test than with antigens conventionally used in the complement fixation (CF) and hemagglutination inhibition tests. A high degree of correlation (P is less than 0.05) was observed between SPRIA anti-immunoglobulin G binding values with the 80,000-molecular-weight nonstructural protein of SLE virus and antibody titers obtained by plaque reduction neutralization and CF with the nonstructural protein. In five of seven human sera in which CF antibody titers to the nonstructural protein were 4 or less, SPRIA testing revealed significant titers of IgG immunoglobulin reactive with this viral protein. The SPRIA test for antibodies reactive with group B togavirus nonstructural protein is as specific and sensitive as the plaque reduction neutralization test for titrating viral antibody in human and animal sera. Antibodies reactive with viral envelope proteins are broadly cross-reactive by the Spria technique, demonstrating both group- and complex-reactive antigenic determinants. The SPRIA test, using wells precoated with antigen, can be completed in 1 day, providing a rapid, highly sensitive test which can be adapted to use in testing a large number of sera.", "contents": "Solid-phase radioimmunoassay for antibodies to flavivirus structural and nonstructural proteins. A micro-solid-phase radioimmunoassay (SPRIA) is described for quantitation of antibodies to purified flaviviruses as well as to the purified envelope glycoprotein and 80,000-molecular-weight viral nonstructural protein. Sera from mice experimentally infected with Saint Louis encephalitis (SLE) virus or from humans after a primary SLE virus infection reacted more specifically with the major viral envelope protein in the SPRIA test than with antigens conventionally used in the complement fixation (CF) and hemagglutination inhibition tests. A high degree of correlation (P is less than 0.05) was observed between SPRIA anti-immunoglobulin G binding values with the 80,000-molecular-weight nonstructural protein of SLE virus and antibody titers obtained by plaque reduction neutralization and CF with the nonstructural protein. In five of seven human sera in which CF antibody titers to the nonstructural protein were 4 or less, SPRIA testing revealed significant titers of IgG immunoglobulin reactive with this viral protein. The SPRIA test for antibodies reactive with group B togavirus nonstructural protein is as specific and sensitive as the plaque reduction neutralization test for titrating viral antibody in human and animal sera. Antibodies reactive with viral envelope proteins are broadly cross-reactive by the Spria technique, demonstrating both group- and complex-reactive antigenic determinants. The SPRIA test, using wells precoated with antigen, can be completed in 1 day, providing a rapid, highly sensitive test which can be adapted to use in testing a large number of sera."} {"id": "PMID:1270143", "title": "Indirect blastogenesis of peripheral blood leukocytes in experimental gingivitis.", "content": "The blastogenic response of peripheral blood leukocytes to lipopolysaccharide (LPS) was followed over a short course of experimental gingivitis, developed in human volunteers who strictly avoided oral hygeine procedures for periods up to 9 days. Eleven young males initially received thorough dental prophylaxes and supervised oral hygeine until they acquired optimal gingival health. At this point, leukocytes (5 X 10(5)) incubated with 1.5 to 25 mug of LPS in serum-free media showed no response as measured by tritiated thymidine uptake. Coincubation of cells with LPS and phytohemagglutinin (PHA), however, caused synergistic enhancement of blastogenesis in every LPS-PHA dose combination tried. With progressive accumulation of dental plaque and the concomitant development of gingival inflammation, this synergistic response was lost and replaced, proportionately, by a direct response to LPS. The leukocyte response to PHA was marginally enhanced with gingivitis.", "contents": "Indirect blastogenesis of peripheral blood leukocytes in experimental gingivitis. The blastogenic response of peripheral blood leukocytes to lipopolysaccharide (LPS) was followed over a short course of experimental gingivitis, developed in human volunteers who strictly avoided oral hygeine procedures for periods up to 9 days. Eleven young males initially received thorough dental prophylaxes and supervised oral hygeine until they acquired optimal gingival health. At this point, leukocytes (5 X 10(5)) incubated with 1.5 to 25 mug of LPS in serum-free media showed no response as measured by tritiated thymidine uptake. Coincubation of cells with LPS and phytohemagglutinin (PHA), however, caused synergistic enhancement of blastogenesis in every LPS-PHA dose combination tried. With progressive accumulation of dental plaque and the concomitant development of gingival inflammation, this synergistic response was lost and replaced, proportionately, by a direct response to LPS. The leukocyte response to PHA was marginally enhanced with gingivitis."} {"id": "PMID:1270144", "title": "Importance of Actinomyces and certain gram-negative anaerobic organisms in the transformation of lymphocytes from patients with periodontal disease.", "content": "Dental plaque deposits are known to be potent stimulants of lymphocyte transformation in patients with periodontal disease but not in normal subjects. Since plaque deposits consist mainly of whole bacteria, the cell walls of the most commonly found organisms in plaque were tested for their capacity to induce lymphocyte transformation. There was a direct correlation between the severity of peridontal disease and the amount of transformation induced by the cell walls of oral bacteria and by solubilized dental plaque. Cord blood leukocytes and lymphocytes from clinically normal people did not respond, which indicates that these stimulants are antigens rather than mitogens. Of the eleven bacteria tested, four members of the family Actinomycetaceae (Actinomyces viscosus, A. israelii, A. naeslundii, and Arachnia propionica), the related Propionibacterium acnes, and an anaerobic gram-negative anaerobic rod (27N). The high prevalence of the former organisms in the mature dental plaque that forms around the gingival crevice area and the potent efficacy with which they stimulate lymphocytes indicates that Actinomyces and certain gram-negative anaerobes may be important etiological agents in chronic periodontal inflammation in man.", "contents": "Importance of Actinomyces and certain gram-negative anaerobic organisms in the transformation of lymphocytes from patients with periodontal disease. Dental plaque deposits are known to be potent stimulants of lymphocyte transformation in patients with periodontal disease but not in normal subjects. Since plaque deposits consist mainly of whole bacteria, the cell walls of the most commonly found organisms in plaque were tested for their capacity to induce lymphocyte transformation. There was a direct correlation between the severity of peridontal disease and the amount of transformation induced by the cell walls of oral bacteria and by solubilized dental plaque. Cord blood leukocytes and lymphocytes from clinically normal people did not respond, which indicates that these stimulants are antigens rather than mitogens. Of the eleven bacteria tested, four members of the family Actinomycetaceae (Actinomyces viscosus, A. israelii, A. naeslundii, and Arachnia propionica), the related Propionibacterium acnes, and an anaerobic gram-negative anaerobic rod (27N). The high prevalence of the former organisms in the mature dental plaque that forms around the gingival crevice area and the potent efficacy with which they stimulate lymphocytes indicates that Actinomyces and certain gram-negative anaerobes may be important etiological agents in chronic periodontal inflammation in man."} {"id": "PMID:1270145", "title": "Modification of resistance of mice to Naegleria fowleri infections.", "content": "Naegleria fowleri, which produces a fatal meningoencephalitis in humans, is also able to produce a progressive and fatal disease in mice. The course of the disease in DUB/ICR mice is dependent upon the infecting dose of organisms, whether administered intraperitoneally (i.p.) or intravenously (i.v.). All of the mice receiving 10(7) trophozoites/mouse i.v. or 4.85 X 10(7) trophozoites/mouse i.p. were killed within 10 days. Escherichia coli O26:B6 lipopolysaccharide, administered at a dose of 1 mg/kg 24 h prior to N. fowleri, afforded some protection for several days after challenge, but by day 8 there was no difference in survival of untreated and endotoxin-treated mice. No significant protection was afforded by a complex of lipid A with concanavalin A (ConA) or bovine serum albumin (BSA) or by dimethylmyristamide-BSA, dimethylmyristamide, BSA, beta-hydroxymyristic acid-ConA, beta-hydroxymyristic acid, ConA, myristic acid-BSA, or myristic acid. Mice surviving primary i.v. or i.p. challenge doses of N. fowleri, 5 X 10(6) and 10(7) trophozoites/mouse, respectively, were highly resistant to rechallenge with an i.v. dose of organisms (5 X 10(6) Naegleria/mouse) that produced uniformly fatal disease in untreated control mice.", "contents": "Modification of resistance of mice to Naegleria fowleri infections. Naegleria fowleri, which produces a fatal meningoencephalitis in humans, is also able to produce a progressive and fatal disease in mice. The course of the disease in DUB/ICR mice is dependent upon the infecting dose of organisms, whether administered intraperitoneally (i.p.) or intravenously (i.v.). All of the mice receiving 10(7) trophozoites/mouse i.v. or 4.85 X 10(7) trophozoites/mouse i.p. were killed within 10 days. Escherichia coli O26:B6 lipopolysaccharide, administered at a dose of 1 mg/kg 24 h prior to N. fowleri, afforded some protection for several days after challenge, but by day 8 there was no difference in survival of untreated and endotoxin-treated mice. No significant protection was afforded by a complex of lipid A with concanavalin A (ConA) or bovine serum albumin (BSA) or by dimethylmyristamide-BSA, dimethylmyristamide, BSA, beta-hydroxymyristic acid-ConA, beta-hydroxymyristic acid, ConA, myristic acid-BSA, or myristic acid. Mice surviving primary i.v. or i.p. challenge doses of N. fowleri, 5 X 10(6) and 10(7) trophozoites/mouse, respectively, were highly resistant to rechallenge with an i.v. dose of organisms (5 X 10(6) Naegleria/mouse) that produced uniformly fatal disease in untreated control mice."} {"id": "PMID:1270146", "title": "Maturation of intestinal defenses against peroral infection with group B coxsackievirus in mice.", "content": "The intestinal tract of adult mice provides effective protection against peroral infection with group B coxsackievirus. This protective function consists of at least two separate components. One is a barrier effect that prevents virus from passing through the mucosal side of the gut into the circulation. It becomes clearly evident at 18 days of life and is present thereafter. The other is a clearance mechanism that acts to eliminate virus from the enteric tract after infection has occurred. This is first demonstrable at about 14 to 18 days and also persists. The appearance of these protective functions coincides with the known development of enzymatic and morphological changes in the gut associated with the transition from suckling to weanling.", "contents": "Maturation of intestinal defenses against peroral infection with group B coxsackievirus in mice. The intestinal tract of adult mice provides effective protection against peroral infection with group B coxsackievirus. This protective function consists of at least two separate components. One is a barrier effect that prevents virus from passing through the mucosal side of the gut into the circulation. It becomes clearly evident at 18 days of life and is present thereafter. The other is a clearance mechanism that acts to eliminate virus from the enteric tract after infection has occurred. This is first demonstrable at about 14 to 18 days and also persists. The appearance of these protective functions coincides with the known development of enzymatic and morphological changes in the gut associated with the transition from suckling to weanling."} {"id": "PMID:1270147", "title": "Temperature-sensitive mutants of rabies virus in mice: a mutant (ts2) revertant mixture selectively pathogenic by the peripheral route of inoculation.", "content": "Analysis of the pathogenic potential in mice of a variety of rabies and rabies serogroup viruses revealed that an apparently revertant population of virus derived from CVS mutant ts 2 had a unique capacity to selectively induce paralytic disease when given by a peripheral [intraplantar (i.pl.)] route of inoculation. Little paralytic disease was induced by high concentrations of virus administered by the intracerebral (i.c.) route, whereas paralytic disease and death were characteristically induced in mice given only a few infectious doses of virus i.c. Disease induced by i.pl. inoculation was dose dependent. Mice frequently survived paralytic disease induced by i. pl. inoculation, with clinical signs often persisting indefinitely; mice surviving i.c. inoculation of high concentrations of virus frequently exhibited chronic nonspecific signs of minor debility. Analysis of the ts 2 virus population indicated that it was composed of a mixture of ts and revertant virions, each with characteristic pathogenic (or nonpatholgnic) propensities, none of which was identical to the original composite ts 2 virus populations. Despite the heterogeneity of the ts 2 virus population, the typical pathogenic pattern of selective pathogenic capicity after i. pl. inoculation at high doses was retained during 11 ocnsecutive passages in suckling mouse brain. ts 2 virus was demonstrated to interfere with the disease-producing capacity of CVS fixed rabies virus when ts 2-CVS mixtures were inoculated i.c. However, attempts to demonstrate a particular propensity for induction in vitro of \"autointerference\" by ts 2 in serial passage in BHK-21 cell culture inoculated at high multiplicity were unsuccessful.", "contents": "Temperature-sensitive mutants of rabies virus in mice: a mutant (ts2) revertant mixture selectively pathogenic by the peripheral route of inoculation. Analysis of the pathogenic potential in mice of a variety of rabies and rabies serogroup viruses revealed that an apparently revertant population of virus derived from CVS mutant ts 2 had a unique capacity to selectively induce paralytic disease when given by a peripheral [intraplantar (i.pl.)] route of inoculation. Little paralytic disease was induced by high concentrations of virus administered by the intracerebral (i.c.) route, whereas paralytic disease and death were characteristically induced in mice given only a few infectious doses of virus i.c. Disease induced by i.pl. inoculation was dose dependent. Mice frequently survived paralytic disease induced by i. pl. inoculation, with clinical signs often persisting indefinitely; mice surviving i.c. inoculation of high concentrations of virus frequently exhibited chronic nonspecific signs of minor debility. Analysis of the ts 2 virus population indicated that it was composed of a mixture of ts and revertant virions, each with characteristic pathogenic (or nonpatholgnic) propensities, none of which was identical to the original composite ts 2 virus populations. Despite the heterogeneity of the ts 2 virus population, the typical pathogenic pattern of selective pathogenic capicity after i. pl. inoculation at high doses was retained during 11 ocnsecutive passages in suckling mouse brain. ts 2 virus was demonstrated to interfere with the disease-producing capacity of CVS fixed rabies virus when ts 2-CVS mixtures were inoculated i.c. However, attempts to demonstrate a particular propensity for induction in vitro of \"autointerference\" by ts 2 in serial passage in BHK-21 cell culture inoculated at high multiplicity were unsuccessful."} {"id": "PMID:1270148", "title": "Interaction of diphtheria toxin and its active subunit, fragment A, with toxin-sensitive and toxin-resistant cells.", "content": "Diphtheria toxin and purified fragment A, the active subunit of the toxin, were tested on toxin-sensitive and permeability class toxin-resistant cultured mammalian cells. Protein synthesis was inhibited to the same degree in sensitive or resistant cells by active concentrations of purified fragment A. In contrast, resistant cells required a concentration of whole toxin 5 to 6 logs greater than that required by sensitive cells to achieve the same degree of inhibition. On a molar basis, the toxicity of fragment A was equivalent to that of whole toxin on resistant cells. These results are evidence for the existence of two independent mechanisms for the entry of toxin or its active moiety into cells. One mechanism is a highly efficient, toxin-specific entry mechanism, involving surface receptor and fragment B-mediated association, and is active in sensitive cells. The other is a less efficient, nonspecific mechanism, probably related to endocytosis, which is operative in sensitive and resistant cells but is inapparent in sensitive cells when they are exposed to whole toxin because of the action of the specific mechanism.", "contents": "Interaction of diphtheria toxin and its active subunit, fragment A, with toxin-sensitive and toxin-resistant cells. Diphtheria toxin and purified fragment A, the active subunit of the toxin, were tested on toxin-sensitive and permeability class toxin-resistant cultured mammalian cells. Protein synthesis was inhibited to the same degree in sensitive or resistant cells by active concentrations of purified fragment A. In contrast, resistant cells required a concentration of whole toxin 5 to 6 logs greater than that required by sensitive cells to achieve the same degree of inhibition. On a molar basis, the toxicity of fragment A was equivalent to that of whole toxin on resistant cells. These results are evidence for the existence of two independent mechanisms for the entry of toxin or its active moiety into cells. One mechanism is a highly efficient, toxin-specific entry mechanism, involving surface receptor and fragment B-mediated association, and is active in sensitive cells. The other is a less efficient, nonspecific mechanism, probably related to endocytosis, which is operative in sensitive and resistant cells but is inapparent in sensitive cells when they are exposed to whole toxin because of the action of the specific mechanism."} {"id": "PMID:1270149", "title": "Antibody-dependent cell-mediated cytotoxicity in cows: comparison of effector cell activity against heterologous erthrocyte and herpesvirus-infected bovine target cells.", "content": "Bovine peripheral blood leukocytes (PBL) and cells collected from the bovine mammary gland were assayed for antibody-dependent cell-mediated cytotoxicity (ADCC) against chicken erythrocyte (CRBC) and bovine herpesvirus-infected bovine kidney cell targets. Bovine antisera were used to sensitize target cells. Both PBL and mammary leukocytes expressed ADCC, with the latter cell population having greater activity against both target cells. Only the CRBC target cells were killed by nonadherent PBL and phagocyte-depleted PBL. Nonadherent mammary leukocytes, rich in monocytes and macrophages, did kill virus-infected target cells. Carbonyl iron-treated mammary leukocytes failed to kill virus-infected targets but could destroy CRBC targets. Antimacrophage serum inhibited lysis of both CRBC and virus-infected targets, but antilymphocyte serum only inhibited CRBC killing. These observations indicated that at least two kinds of cells could mediate ADCC against CRBC but only cells of the mononuclear phagocytic series could kill virus-infected target cells. The herpesvirus-infected target cells became susceptible to ADCC 9 h after virus infection. A case is made for investigating the phenomenon of ADCC using in vitro systems that closely mimic the in vivo situation. The possible role of the ADCC mechanism as instrumental in causing recovery from herpesvirus infections is discussed.", "contents": "Antibody-dependent cell-mediated cytotoxicity in cows: comparison of effector cell activity against heterologous erthrocyte and herpesvirus-infected bovine target cells. Bovine peripheral blood leukocytes (PBL) and cells collected from the bovine mammary gland were assayed for antibody-dependent cell-mediated cytotoxicity (ADCC) against chicken erythrocyte (CRBC) and bovine herpesvirus-infected bovine kidney cell targets. Bovine antisera were used to sensitize target cells. Both PBL and mammary leukocytes expressed ADCC, with the latter cell population having greater activity against both target cells. Only the CRBC target cells were killed by nonadherent PBL and phagocyte-depleted PBL. Nonadherent mammary leukocytes, rich in monocytes and macrophages, did kill virus-infected target cells. Carbonyl iron-treated mammary leukocytes failed to kill virus-infected targets but could destroy CRBC targets. Antimacrophage serum inhibited lysis of both CRBC and virus-infected targets, but antilymphocyte serum only inhibited CRBC killing. These observations indicated that at least two kinds of cells could mediate ADCC against CRBC but only cells of the mononuclear phagocytic series could kill virus-infected target cells. The herpesvirus-infected target cells became susceptible to ADCC 9 h after virus infection. A case is made for investigating the phenomenon of ADCC using in vitro systems that closely mimic the in vivo situation. The possible role of the ADCC mechanism as instrumental in causing recovery from herpesvirus infections is discussed."} {"id": "PMID:1270150", "title": "Different effects of phytohemagglutinin-activated lymphocytes and their culture supernatants on macrophage function.", "content": "When rabbit peritoneal exudate cells were incubated for 24 and 48 h with phytohemagglutinin-activated lymphocytes or their culture supernatants, two times as many cells remained adherent to culture slides as in the controls. More spreading cells were found among the adherent cells in the stimulated cultures. Eighty percent of spreading cells that were induced by supernatants were negative or faintly positive for beta-galactosidase. On the other hand, half of the spreading cells induced by activated lymphocytes were positive (1+ to 4+) for beta-lymphocytes and their supernatants. Under similar conditions, unstimulated peritoneal cells showed less marked activation. These findings show that macrophages can appear morphologically activated and yet not be enzymatically activated by lymphokines. Possible mechanisms of direct interaction of activated lymphocytes and macrophages are discussed.", "contents": "Different effects of phytohemagglutinin-activated lymphocytes and their culture supernatants on macrophage function. When rabbit peritoneal exudate cells were incubated for 24 and 48 h with phytohemagglutinin-activated lymphocytes or their culture supernatants, two times as many cells remained adherent to culture slides as in the controls. More spreading cells were found among the adherent cells in the stimulated cultures. Eighty percent of spreading cells that were induced by supernatants were negative or faintly positive for beta-galactosidase. On the other hand, half of the spreading cells induced by activated lymphocytes were positive (1+ to 4+) for beta-lymphocytes and their supernatants. Under similar conditions, unstimulated peritoneal cells showed less marked activation. These findings show that macrophages can appear morphologically activated and yet not be enzymatically activated by lymphokines. Possible mechanisms of direct interaction of activated lymphocytes and macrophages are discussed."} {"id": "PMID:1270151", "title": "Fusobacterium necrophorum infection in mice as a model for the study of liver abscess formation and induction of immunity.", "content": "A mouse model is described in which intraperitoneal injection of Fusobacterium necrophorum results in chronic liver abscesses. Viable bacterial counts from mouse lung, liver, and spleen were obtained after whole organ homogenization. From 2 h to 5 days postchallenge, liver was found to contain more bacteria than lung on a per gram basis. Bacterial counts from liver and spleen were about the same during the first 8 h; thereafter liver was found to contain more bacteria. By day 13, though bacterial counts were equivalent in the three organs, abscesses were only observed in liver. This predilection for the liver may be due to a nutritional and/or microenvironmental factor(s). Blood cultures of infected mice revealed a general lack of bacteremia. Extended immunization with formalin-killed cells was found to protect mice against F. necrophorum infection.", "contents": "Fusobacterium necrophorum infection in mice as a model for the study of liver abscess formation and induction of immunity. A mouse model is described in which intraperitoneal injection of Fusobacterium necrophorum results in chronic liver abscesses. Viable bacterial counts from mouse lung, liver, and spleen were obtained after whole organ homogenization. From 2 h to 5 days postchallenge, liver was found to contain more bacteria than lung on a per gram basis. Bacterial counts from liver and spleen were about the same during the first 8 h; thereafter liver was found to contain more bacteria. By day 13, though bacterial counts were equivalent in the three organs, abscesses were only observed in liver. This predilection for the liver may be due to a nutritional and/or microenvironmental factor(s). Blood cultures of infected mice revealed a general lack of bacteremia. Extended immunization with formalin-killed cells was found to protect mice against F. necrophorum infection."} {"id": "PMID:1270152", "title": "Morphological and steroidogenic changes in cultured adrenal tumor cells induced by a subunit of cholera enterotoxin.", "content": "A purified subunit of the cholera enterotoxin molecule was found to have morphological and steroidogenic inducing effects similar to those induced by the native enterotoxin on monolayer tissue cultures of Y1 adrenal tumor cells, although 1,000 times more subunit than toxin (weight basis) was required for maximal effects. In contrast to the whole toxin, the effects of the active subunit could not be prevented by prior incubation with either Gm1 ganglioside or with antibodies directed against choleragenoid (the binding subunit). These results suggest that different receptor sites may exist on cells for the binding and for the active subunits of cholera enterotoxin and/or that the active toxin fragment may exert its effects after gaining access to the intracellular compartment.", "contents": "Morphological and steroidogenic changes in cultured adrenal tumor cells induced by a subunit of cholera enterotoxin. A purified subunit of the cholera enterotoxin molecule was found to have morphological and steroidogenic inducing effects similar to those induced by the native enterotoxin on monolayer tissue cultures of Y1 adrenal tumor cells, although 1,000 times more subunit than toxin (weight basis) was required for maximal effects. In contrast to the whole toxin, the effects of the active subunit could not be prevented by prior incubation with either Gm1 ganglioside or with antibodies directed against choleragenoid (the binding subunit). These results suggest that different receptor sites may exist on cells for the binding and for the active subunits of cholera enterotoxin and/or that the active toxin fragment may exert its effects after gaining access to the intracellular compartment."} {"id": "PMID:1270153", "title": "Streptococcus mutans dextransucrase: availability of disaggregated enzyme after growth in a chemically defined medium.", "content": "The soluble dextransucrase (EC 2.4.1.5) activity produced by Streptococcus mutans strain 6715 during growth on a chemically defined synthetic medium (FMS) was compared to enzyme from glucose broth cultures (TSB). Growth on the two media was similar. The specific activity of ammonium sulfate-precipitated FMC enzyme was 17 times greater than similar TSB enzyme preparations. The FMC enzyme was stimulated 11-fold, whereas the TSB enzyme was stimulated 1.2-fold by the addition of exogenous primer dextran. In contrast to the TSB enzyme, the FMC activity could be disaggregated to a low-molecular-weight form by 1 M salt. Thus, low-molecular-weight S. mutans dextransucrase activity free of contaminating primer glucan may be readily obtained after growth of the bacterium in a chemically defined sucrose-free medium.", "contents": "Streptococcus mutans dextransucrase: availability of disaggregated enzyme after growth in a chemically defined medium. The soluble dextransucrase (EC 2.4.1.5) activity produced by Streptococcus mutans strain 6715 during growth on a chemically defined synthetic medium (FMS) was compared to enzyme from glucose broth cultures (TSB). Growth on the two media was similar. The specific activity of ammonium sulfate-precipitated FMC enzyme was 17 times greater than similar TSB enzyme preparations. The FMC enzyme was stimulated 11-fold, whereas the TSB enzyme was stimulated 1.2-fold by the addition of exogenous primer dextran. In contrast to the TSB enzyme, the FMC activity could be disaggregated to a low-molecular-weight form by 1 M salt. Thus, low-molecular-weight S. mutans dextransucrase activity free of contaminating primer glucan may be readily obtained after growth of the bacterium in a chemically defined sucrose-free medium."} {"id": "PMID:1270154", "title": "Immunoglobulin-bearing cells in lungs of mice infected with influenza virus.", "content": "In sequential studies of cellular infiltrates from influenza-infected mouse lungs, increased populations of lymphocytes with surface immunoglobulins were observed, and immunoglobulin A-bearing cells exhibited the greatest relative increase.", "contents": "Immunoglobulin-bearing cells in lungs of mice infected with influenza virus. In sequential studies of cellular infiltrates from influenza-infected mouse lungs, increased populations of lymphocytes with surface immunoglobulins were observed, and immunoglobulin A-bearing cells exhibited the greatest relative increase."} {"id": "PMID:1270155", "title": "Strain-dependent differences in murine susceptibility to toxoplasma.", "content": "Susceptibility of seven inbred and outbred strains of mice to infection with trophozoites of Toxoplasma gondii at two different doses was determined. Stroking strain differences in susceptibility and changes of susceptibility with dosage change were seen. The data are consistent with the hypothesis that this may be due to genetic factors.", "contents": "Strain-dependent differences in murine susceptibility to toxoplasma. Susceptibility of seven inbred and outbred strains of mice to infection with trophozoites of Toxoplasma gondii at two different doses was determined. Stroking strain differences in susceptibility and changes of susceptibility with dosage change were seen. The data are consistent with the hypothesis that this may be due to genetic factors."} {"id": "PMID:1270156", "title": "Studies on allergens of Dermatophagoides pteronyssinus by direct and indirect RAST.", "content": "Dermatophagoides pteronyssinus (DP) extract was fractionated by Sephadex G-75 and liquid isoelectric focusing (IEF) and the allergenic activity of different fractions was monitored by direct and indirect RAST. The fractionation on Sephadex G-75 showed that the allergenic activity of DP extract was related to wide molecular weight spectrum components, even though the maximum amount was recovered in effluent that contained protein with a molecular weight ranging between 25,000 and 12,500 daltons. By fractionation of the mite extract on IEF, three main peaks of allergenic activity (pI less than 3.0; pI = 4.3 +/- 0.25; pI = 6.4 +/- 0.25) were found. Cross-inhibition experiments showed a high degree of cross-reactivity between allergenic material eluted in very distant regions of molecular weight or isoelectric point. The allergenic activity of unfractionated mite extract and of its IEF fractions was destroyed by pronase - but not by neuraminidase - treatment. These results suggest that DP extract probably contains one main allergen existing in multiple molecular forms rather than several distinct allergens and that a protein moiety of the allergen is necessary for the combination with IgE.", "contents": "Studies on allergens of Dermatophagoides pteronyssinus by direct and indirect RAST. Dermatophagoides pteronyssinus (DP) extract was fractionated by Sephadex G-75 and liquid isoelectric focusing (IEF) and the allergenic activity of different fractions was monitored by direct and indirect RAST. The fractionation on Sephadex G-75 showed that the allergenic activity of DP extract was related to wide molecular weight spectrum components, even though the maximum amount was recovered in effluent that contained protein with a molecular weight ranging between 25,000 and 12,500 daltons. By fractionation of the mite extract on IEF, three main peaks of allergenic activity (pI less than 3.0; pI = 4.3 +/- 0.25; pI = 6.4 +/- 0.25) were found. Cross-inhibition experiments showed a high degree of cross-reactivity between allergenic material eluted in very distant regions of molecular weight or isoelectric point. The allergenic activity of unfractionated mite extract and of its IEF fractions was destroyed by pronase - but not by neuraminidase - treatment. These results suggest that DP extract probably contains one main allergen existing in multiple molecular forms rather than several distinct allergens and that a protein moiety of the allergen is necessary for the combination with IgE."} {"id": "PMID:1270157", "title": "Effect of insulin and alloxan diabetes on carrageenin inflammation in rats.", "content": "Some hypersensitivity reactions and allergic responses are known to be increased by insulin treatment and decreased in diabetes. In contrast, the present experiments showed that paw swelling induced by carrageenin in rats was inhibited by insulin. The anti-inflammatory activity, to some extent, paralleled the dose applied and did not appear to be due to hypoglycaemia. Alloxan diabetes in turn increased the vascular response to carrageenin and abolished the anti-inflammatory effect of insulin. The experiments call attention to the possible significance of insulin in the regulation of the acute non-immune inflammatory process.", "contents": "Effect of insulin and alloxan diabetes on carrageenin inflammation in rats. Some hypersensitivity reactions and allergic responses are known to be increased by insulin treatment and decreased in diabetes. In contrast, the present experiments showed that paw swelling induced by carrageenin in rats was inhibited by insulin. The anti-inflammatory activity, to some extent, paralleled the dose applied and did not appear to be due to hypoglycaemia. Alloxan diabetes in turn increased the vascular response to carrageenin and abolished the anti-inflammatory effect of insulin. The experiments call attention to the possible significance of insulin in the regulation of the acute non-immune inflammatory process."} {"id": "PMID:1270158", "title": "Anaphylactoid reactions in connection with infusion of invert sugar solutions are due to macromolecular contaminants.", "content": "13 untoward mold anaphylactoid reactions were observed in patients infused with invert sugar solutions in Sweden during a 7-month period in 1973: an incidence of 1/31,000 infusions. Immunological and physicochemical analysis of invert sugar solutions and of the raw material, sucrose, revealed traces of native alpha-1,6-glucan with molecular weight of 10-100 millions as contaminant. This indicates, that the sucrose had been exposed to microbial contamination during its manufacture from sugar-beet or sugar-cane. Reversed single radial immunodiffusion was used for alpha-1,6-glucan detection and screening of all sucrose batches. Rejection of contaminated sucrose as raw material reduced the incidence of anaphylactoid invert sugar reactions to about 1/575,000 infusions. Examination of all sucrose raw material for traces of crude alpha-1,6-glucan is recommended as a test for detection of microbial contamination.", "contents": "Anaphylactoid reactions in connection with infusion of invert sugar solutions are due to macromolecular contaminants. 13 untoward mold anaphylactoid reactions were observed in patients infused with invert sugar solutions in Sweden during a 7-month period in 1973: an incidence of 1/31,000 infusions. Immunological and physicochemical analysis of invert sugar solutions and of the raw material, sucrose, revealed traces of native alpha-1,6-glucan with molecular weight of 10-100 millions as contaminant. This indicates, that the sucrose had been exposed to microbial contamination during its manufacture from sugar-beet or sugar-cane. Reversed single radial immunodiffusion was used for alpha-1,6-glucan detection and screening of all sucrose batches. Rejection of contaminated sucrose as raw material reduced the incidence of anaphylactoid invert sugar reactions to about 1/575,000 infusions. Examination of all sucrose raw material for traces of crude alpha-1,6-glucan is recommended as a test for detection of microbial contamination."} {"id": "PMID:1270159", "title": "Lymphocyte stimulation and plasma inhibition in patients with malignant neoplasms. A comparative study with three mitogens.", "content": "The blastogenic response of lymphocytes from patients with malignant neoplasms was evaluated by stimulation with three phytomitogens (PHA, PWM, and Con A). The response of patient lymphocytes to all three mitogens was significantly lower than that of control lymphocytes, and most patients with abnormal PHA responses also responded abnormally to PWM and Con A. However, a few patients with normal PHA responses were abnormal to Con A, suggesting the suppression of a Con A-sensitive population. The observation that PWM responses were abnormal in patients with lowered PHA lymphocyte stimulation indicates that both T and B lymphocyte mitogen responses were suppressed in these patients. Plasma from patients was capable of either inhibiting or enhancing lymphocyte mitogen stimulation. However, inhibitory plasmas were generally from patients with abnormal mitogen responses.", "contents": "Lymphocyte stimulation and plasma inhibition in patients with malignant neoplasms. A comparative study with three mitogens. The blastogenic response of lymphocytes from patients with malignant neoplasms was evaluated by stimulation with three phytomitogens (PHA, PWM, and Con A). The response of patient lymphocytes to all three mitogens was significantly lower than that of control lymphocytes, and most patients with abnormal PHA responses also responded abnormally to PWM and Con A. However, a few patients with normal PHA responses were abnormal to Con A, suggesting the suppression of a Con A-sensitive population. The observation that PWM responses were abnormal in patients with lowered PHA lymphocyte stimulation indicates that both T and B lymphocyte mitogen responses were suppressed in these patients. Plasma from patients was capable of either inhibiting or enhancing lymphocyte mitogen stimulation. However, inhibitory plasmas were generally from patients with abnormal mitogen responses."} {"id": "PMID:1270160", "title": "Modulation of the release of SRS-A from bovine lung in vitro by several autonomic and autacoid agents.", "content": "The immunological release of slow-reacting substance of anaphylaxis (SRS-A) from bovine lung is modulated by several autonomic and autacoid agents. Isoproterenol, a beta-adrenergic agonist, inhibited release of SRS-A, as did cyclic AMP. Phenylephrine also inhibited SRS-A release but through alpha-adrenergic mechanisms. This is in contrast to observations in human lung. Carbachol enhanced the release of bovine SRS-A. Histamine inhibited SRS-A release through the H2-receptor. Dopamine enhanced the release of SRS-A by means of a dopaminergic receptor. 5-HT did not significantly modulate SRS-A release.", "contents": "Modulation of the release of SRS-A from bovine lung in vitro by several autonomic and autacoid agents. The immunological release of slow-reacting substance of anaphylaxis (SRS-A) from bovine lung is modulated by several autonomic and autacoid agents. Isoproterenol, a beta-adrenergic agonist, inhibited release of SRS-A, as did cyclic AMP. Phenylephrine also inhibited SRS-A release but through alpha-adrenergic mechanisms. This is in contrast to observations in human lung. Carbachol enhanced the release of bovine SRS-A. Histamine inhibited SRS-A release through the H2-receptor. Dopamine enhanced the release of SRS-A by means of a dopaminergic receptor. 5-HT did not significantly modulate SRS-A release."} {"id": "PMID:1270161", "title": "Allergic contact dermatitis to low molecular weight allergens in the chicken.", "content": "We have produced allergic contact dermatitis (ACD) to low molecular weight allergens in the chicken. Sensitization was induced by the application of a high concentration of allergen to a site on the comb previously treated with dimethyl sulfoxide. Challenge, which was made on the wattle with a nonirritating concentration of allergen, resulted in a dermatitis that was grossly and histologically similar to ACD in mammals. Chickens sensitized to oxazolone reacted to that allergen and not to picryl chloride, and conversely. This model provides a unique system wherein to study the T-cell and B-cell contributions to the generation, maintainance and expression of the ACD response.", "contents": "Allergic contact dermatitis to low molecular weight allergens in the chicken. We have produced allergic contact dermatitis (ACD) to low molecular weight allergens in the chicken. Sensitization was induced by the application of a high concentration of allergen to a site on the comb previously treated with dimethyl sulfoxide. Challenge, which was made on the wattle with a nonirritating concentration of allergen, resulted in a dermatitis that was grossly and histologically similar to ACD in mammals. Chickens sensitized to oxazolone reacted to that allergen and not to picryl chloride, and conversely. This model provides a unique system wherein to study the T-cell and B-cell contributions to the generation, maintainance and expression of the ACD response."} {"id": "PMID:1270169", "title": "Stabilisation, co-ordination and structuralisation in the integrated automation of complex systems.", "content": "The objectives of structural parallelism and composition of modules in integrated automation, as well as in the tracking approach based on the distance between the systems, form the base of a methodology of analysis and synthesis of the control of complex systems. The unit control is founded on the tracking of trajectories determined by the behaviour of the whole complex global system. The control system is based on the desire to attain the imposed objectives, as well as a participation in the efforts of other systems. These properties of each decision centre thus formed, permit the stabilisation of the whole interconnected global system. This global system can easily be co-ordinated or restructured by the directing decision centre which disposed of a global model.", "contents": "Stabilisation, co-ordination and structuralisation in the integrated automation of complex systems. The objectives of structural parallelism and composition of modules in integrated automation, as well as in the tracking approach based on the distance between the systems, form the base of a methodology of analysis and synthesis of the control of complex systems. The unit control is founded on the tracking of trajectories determined by the behaviour of the whole complex global system. The control system is based on the desire to attain the imposed objectives, as well as a participation in the efforts of other systems. These properties of each decision centre thus formed, permit the stabilisation of the whole interconnected global system. This global system can easily be co-ordinated or restructured by the directing decision centre which disposed of a global model."} {"id": "PMID:1270170", "title": "The derivation of second degree rate equations arising from two-substrate, two-product enzyme catalysed reactions whose catalytic cycle is branched.", "content": "A selection of two-substrate, two-product enzyme catalysed reactions with alternate catalytic cycles and second degree rate equations was examined by the computer program described by Kinderlerer and Ainsworth (1976). It is shown that the numerator terms of the rate equations are particularly simple, easy to derive and capable of creating a broad division of the mechanisms considered. THE NUMERATOR TERMS ALSO HAVE THE ADVANTAGE OF BEING UNAFFECTED BY DEAD END INHIBITION OR THE PRESENCE OF Theorell-Chance reactions. It is then shown that the relatively small group of mechanisms, isolated by the numerator analysis, can be distinguished from each other by considering the denominator terms of the rate equation that are second degree in the concentration of the varied substrate.", "contents": "The derivation of second degree rate equations arising from two-substrate, two-product enzyme catalysed reactions whose catalytic cycle is branched. A selection of two-substrate, two-product enzyme catalysed reactions with alternate catalytic cycles and second degree rate equations was examined by the computer program described by Kinderlerer and Ainsworth (1976). It is shown that the numerator terms of the rate equations are particularly simple, easy to derive and capable of creating a broad division of the mechanisms considered. THE NUMERATOR TERMS ALSO HAVE THE ADVANTAGE OF BEING UNAFFECTED BY DEAD END INHIBITION OR THE PRESENCE OF Theorell-Chance reactions. It is then shown that the relatively small group of mechanisms, isolated by the numerator analysis, can be distinguished from each other by considering the denominator terms of the rate equation that are second degree in the concentration of the varied substrate."} {"id": "PMID:1270171", "title": "Programming for the inexperienced users: machine independence and free-format input.", "content": "Two programming techniques which can make the use of computers less troublesome to inexperienced users are described. The first has the object of making programs readily transferable from one machine to another, thereby facilitating transfer of programs between individuals. The second consists of a FORTRAN subroutine, described in detail, which allows numbers to be read by a program without being confined to specific columns on a punched card, thereby greatly simplifying data preparation.", "contents": "Programming for the inexperienced users: machine independence and free-format input. Two programming techniques which can make the use of computers less troublesome to inexperienced users are described. The first has the object of making programs readily transferable from one machine to another, thereby facilitating transfer of programs between individuals. The second consists of a FORTRAN subroutine, described in detail, which allows numbers to be read by a program without being confined to specific columns on a punched card, thereby greatly simplifying data preparation."} {"id": "PMID:1270172", "title": "Convolution computer processing of the brain electriacl image transmission.", "content": "A propagation model of electrical activities between the cerebral cortex and the scalp is presented in this paper. This work is based on a hypothesis of a distribution of cortical sources in a non-uniform dipolar sheet. The general field equations show that the electrical image of the cortex on the scalp is given by the convolution of the cortical potential and a transfer function. We then present several numerical evaluations with respect to the attenuation of the signal, the visual field of the electrodes and the approximation errors that have been introduced. Simulation experiments then enable us to test the behaviour of the model in comparison with complex electrical activities.", "contents": "Convolution computer processing of the brain electriacl image transmission. A propagation model of electrical activities between the cerebral cortex and the scalp is presented in this paper. This work is based on a hypothesis of a distribution of cortical sources in a non-uniform dipolar sheet. The general field equations show that the electrical image of the cortex on the scalp is given by the convolution of the cortical potential and a transfer function. We then present several numerical evaluations with respect to the attenuation of the signal, the visual field of the electrodes and the approximation errors that have been introduced. Simulation experiments then enable us to test the behaviour of the model in comparison with complex electrical activities."} {"id": "PMID:1270173", "title": "Computer-aided investigations of respiratory data.", "content": "In the first part of this paper a computerised evaluation of plethysmographic signals is presented. The off-line processing described eliminates some erroneous simplifications that routine plethysmography is bound to involve. (1) A subtraction of the box pressure baseline permits measurements with perfectly sealed constant volume plethysmographs even in the case of thermal disequilibrium. (2) Alveolar pressure is computed from the box pressure signal, using instantaneous values of the intrathoracic gas volume. (3) This technique enables one to utilise all the measured data for determinations of airway resistance and viscous work, thus yielding more exact values as compared to the graphic evaluations. In Part 2 a three-parameter model of transpulmonary mechanics, applied to fit data of cat experiments, is described. The aim of this study is to demonstrate how transpulmonary parameters (static pleural pressure, compliance and resistance) are modified by the actual state of the pulmonary vascular bed.", "contents": "Computer-aided investigations of respiratory data. In the first part of this paper a computerised evaluation of plethysmographic signals is presented. The off-line processing described eliminates some erroneous simplifications that routine plethysmography is bound to involve. (1) A subtraction of the box pressure baseline permits measurements with perfectly sealed constant volume plethysmographs even in the case of thermal disequilibrium. (2) Alveolar pressure is computed from the box pressure signal, using instantaneous values of the intrathoracic gas volume. (3) This technique enables one to utilise all the measured data for determinations of airway resistance and viscous work, thus yielding more exact values as compared to the graphic evaluations. In Part 2 a three-parameter model of transpulmonary mechanics, applied to fit data of cat experiments, is described. The aim of this study is to demonstrate how transpulmonary parameters (static pleural pressure, compliance and resistance) are modified by the actual state of the pulmonary vascular bed."} {"id": "PMID:1270174", "title": "Detection of tumor-associated antigen in human melanoma cell line supernatants.", "content": "Spent tissue culture medium (CDM-S) removed from a single cell line of human malignant melanoma grown in serum-free CDM, contained tumor-associated antigenic activity. Antibodies to CDM-S measured by complement fixation were detected in 44% (31/70) melanoma, 55% (15/27) sarcoma, 63% (24/38) carcinoma and 15% (11/72) normal sera. Delayed cutaneous hypersensitivity reactions (DCHR) were demonstrated in 4/5 melanoma patients at a 500 mug dose, 3/5 at a 100 mug dose and in 1/7 carcinoma patients at the 500 mug dose. One ml of CDM-S was shown to contain antigen equivalent to that obtained from the membranes of 2.9 X 10(7) tissue-cultured melanoma cells. After purification, 84% (16/19) sera from melanoma patients, 66% (12/18) from sarcoma and carcinoma patients and 8% (2/26) from normal controls were positive to the antigen by complement fixation.", "contents": "Detection of tumor-associated antigen in human melanoma cell line supernatants. Spent tissue culture medium (CDM-S) removed from a single cell line of human malignant melanoma grown in serum-free CDM, contained tumor-associated antigenic activity. Antibodies to CDM-S measured by complement fixation were detected in 44% (31/70) melanoma, 55% (15/27) sarcoma, 63% (24/38) carcinoma and 15% (11/72) normal sera. Delayed cutaneous hypersensitivity reactions (DCHR) were demonstrated in 4/5 melanoma patients at a 500 mug dose, 3/5 at a 100 mug dose and in 1/7 carcinoma patients at the 500 mug dose. One ml of CDM-S was shown to contain antigen equivalent to that obtained from the membranes of 2.9 X 10(7) tissue-cultured melanoma cells. After purification, 84% (16/19) sera from melanoma patients, 66% (12/18) from sarcoma and carcinoma patients and 8% (2/26) from normal controls were positive to the antigen by complement fixation."} {"id": "PMID:1270175", "title": "Assessment of cell-mediated immunity to malignant mesothelioma by microcytotoxicity tests.", "content": "Cell cultures were established from pleural effusions of patients with pleural mesothelioma, and peripheral mononuclear effector cells were tested for cytotoxicity against these cells by means of microcytotoxicity assay. Effector cells were obtained from normal healthy donors and from persons exposed occupationally to asbestos, including apparently healthy persons, patients with benign pleural conditions and patients with malignant mesothelioma. The overall incidence of cytotoxicity was low, and there was no evidence of increased cytotoxicity in mesothelioma patients or other asbestos-exposed donors. It is concluded that little or no tumour-directed cell-mediated immunity is detectable against malignant mesothelioma by microcytotoxicity methods.", "contents": "Assessment of cell-mediated immunity to malignant mesothelioma by microcytotoxicity tests. Cell cultures were established from pleural effusions of patients with pleural mesothelioma, and peripheral mononuclear effector cells were tested for cytotoxicity against these cells by means of microcytotoxicity assay. Effector cells were obtained from normal healthy donors and from persons exposed occupationally to asbestos, including apparently healthy persons, patients with benign pleural conditions and patients with malignant mesothelioma. The overall incidence of cytotoxicity was low, and there was no evidence of increased cytotoxicity in mesothelioma patients or other asbestos-exposed donors. It is concluded that little or no tumour-directed cell-mediated immunity is detectable against malignant mesothelioma by microcytotoxicity methods."} {"id": "PMID:1270176", "title": "Mortality from cancer of the uterus in Canada and its relationship to screening for cancer of the cervix.", "content": "Age-standardized death rates at ages 30-64 from cancer of the uterus in the 10 provinces of Canada have been assessed in 1950-52, 1960-62 and 1970-72, and changes in rats over these periods related to screening for cancer of the cervix and variables derived from the censuses of 1961 and 1971. Death rates at the county and census division level have also been assessed for the provinces of Nova Scotia, Quebec, Ontario, Manitoba and Alberta for 1960-62 and 1970-72 and related to screening and census-derived variables. There is little indication of a contribution of screening to the fall in death rates that occurred in eight of the 10 provinces from 1950-52 to 1960-62. There is, however, evidence of an important and significant contribution of the intensity of screening (as indicated by the number of cervical cytology examinations conducted in 1966 expressed as a rate per 1,000 female population aged 20 or more) to the fall in death rates at both the provincial and county or census division levels from 1960-62 to 1970-72, and this effect is not abolished by taking the census-derived variables into account. It is concluded that a significant effect of intensity of screening on the reduction in mortality from cancer of the uterus in Canada in the age-group 30-64 over the period 1960-62 to 1970-72 has been demonstrated.", "contents": "Mortality from cancer of the uterus in Canada and its relationship to screening for cancer of the cervix. Age-standardized death rates at ages 30-64 from cancer of the uterus in the 10 provinces of Canada have been assessed in 1950-52, 1960-62 and 1970-72, and changes in rats over these periods related to screening for cancer of the cervix and variables derived from the censuses of 1961 and 1971. Death rates at the county and census division level have also been assessed for the provinces of Nova Scotia, Quebec, Ontario, Manitoba and Alberta for 1960-62 and 1970-72 and related to screening and census-derived variables. There is little indication of a contribution of screening to the fall in death rates that occurred in eight of the 10 provinces from 1950-52 to 1960-62. There is, however, evidence of an important and significant contribution of the intensity of screening (as indicated by the number of cervical cytology examinations conducted in 1966 expressed as a rate per 1,000 female population aged 20 or more) to the fall in death rates at both the provincial and county or census division levels from 1960-62 to 1970-72, and this effect is not abolished by taking the census-derived variables into account. It is concluded that a significant effect of intensity of screening on the reduction in mortality from cancer of the uterus in Canada in the age-group 30-64 over the period 1960-62 to 1970-72 has been demonstrated."} {"id": "PMID:1270177", "title": "Rapid development of hyperplastic nodules and cirrhosis in the liver of rats treated concurrently with thioacetamide and the pyrrolizidine alkaloid lasiocarpine.", "content": "Pyrrolizidine alkaloids have long been considered to be hepatotoxic in man as well as in grazing animals. To investigate the effect of liver cell division induced by thioacetamide on the hepatic changes induced by these alkaloids, rats were treated concurrently with thioacetamide and the pyrrolizidine alkaloid lasiocarpine. Thioacetamide was given intraperitoneally in a dose of 50 mg/kg b. wt twice weekly and lasiocarpine was administered in the diet at a concentration of 50 ppm. At 15 weeks, the combination of thioacetamide and lasiocarpine produced numerous grossly visible grey nodules in livers of 26 of 30 rats. Microscopically, these livers revealed a severe degree of postnecrotic cirrhosis and numerous hyperplastic nodules. The cells in most nodules were arranged in solid sheets or in a trabecular pattern and shown atypia, mitosis and hyperchromasia. In contrast, there was no evidence of cirrhosis or nodule formation in livers of animals treated with either lasiocarpine or thioacetamide alone. The rapid development of liver lesions in rats treated simultaneously with low doses of lasiocarpine and thioacetamide suggests that cell proliferation accentuates the development of neoplasia.\u0142", "contents": "Rapid development of hyperplastic nodules and cirrhosis in the liver of rats treated concurrently with thioacetamide and the pyrrolizidine alkaloid lasiocarpine. Pyrrolizidine alkaloids have long been considered to be hepatotoxic in man as well as in grazing animals. To investigate the effect of liver cell division induced by thioacetamide on the hepatic changes induced by these alkaloids, rats were treated concurrently with thioacetamide and the pyrrolizidine alkaloid lasiocarpine. Thioacetamide was given intraperitoneally in a dose of 50 mg/kg b. wt twice weekly and lasiocarpine was administered in the diet at a concentration of 50 ppm. At 15 weeks, the combination of thioacetamide and lasiocarpine produced numerous grossly visible grey nodules in livers of 26 of 30 rats. Microscopically, these livers revealed a severe degree of postnecrotic cirrhosis and numerous hyperplastic nodules. The cells in most nodules were arranged in solid sheets or in a trabecular pattern and shown atypia, mitosis and hyperchromasia. In contrast, there was no evidence of cirrhosis or nodule formation in livers of animals treated with either lasiocarpine or thioacetamide alone. The rapid development of liver lesions in rats treated simultaneously with low doses of lasiocarpine and thioacetamide suggests that cell proliferation accentuates the development of neoplasia.\u0142"} {"id": "PMID:1270178", "title": "Interaction of antibody and cell surface localized antigen.", "content": "The changes occurring in the expression of a membrane-associated antigen following binding of specific antibodies and the fate of the bound antibodies were investigated. Daudi cells, carrying membrane 7S IgM molecules, were coated with radio-labelled anti-IgM antibodies and incubated under culture conditions at 37degrees C. Within 10 h, more than 80% of the cellbound radioactivity was shed from the cells into the culture medium. Concomitantly, IgM molecules were lost, as the cells had a diminished ability to bind a new aliquot of antibody. This phenomenon occurred also when the antibody was used at a low concentration, i.e. did not saturate the cell-surface antigens. The precipitability of the antibody released from the cells with 10% TCA and 40% saturated ammonium sulphate was lower than that of native antibody, indicating some degradation. Also, shed antibody could rebind to fresh Daudi cells less efficiently than native antibody. The presence of immune complexes in the culture supernatants was indicated by the following results: (1) some of the shed radioactivity could bind to IgM-negative but Fc receptor-bearing cells; and (2) immune precipitates of sheep anti-IgM shed from 3H-leucine labelled Daudi cells and of rabbit anti-sheep IgG antibodies contained 3H activity.", "contents": "Interaction of antibody and cell surface localized antigen. The changes occurring in the expression of a membrane-associated antigen following binding of specific antibodies and the fate of the bound antibodies were investigated. Daudi cells, carrying membrane 7S IgM molecules, were coated with radio-labelled anti-IgM antibodies and incubated under culture conditions at 37degrees C. Within 10 h, more than 80% of the cellbound radioactivity was shed from the cells into the culture medium. Concomitantly, IgM molecules were lost, as the cells had a diminished ability to bind a new aliquot of antibody. This phenomenon occurred also when the antibody was used at a low concentration, i.e. did not saturate the cell-surface antigens. The precipitability of the antibody released from the cells with 10% TCA and 40% saturated ammonium sulphate was lower than that of native antibody, indicating some degradation. Also, shed antibody could rebind to fresh Daudi cells less efficiently than native antibody. The presence of immune complexes in the culture supernatants was indicated by the following results: (1) some of the shed radioactivity could bind to IgM-negative but Fc receptor-bearing cells; and (2) immune precipitates of sheep anti-IgM shed from 3H-leucine labelled Daudi cells and of rabbit anti-sheep IgG antibodies contained 3H activity."} {"id": "PMID:1270179", "title": "Interferon and murine leukemia. VII. Therapeutic effect of interferon preparations after diagnosis of lymphoma in AKR mice.", "content": "Daily administration of potent mouse interferon preparations, begun after clinical diagnosis of lymphoma in AKR mice, increased average survival by approximately 100%. Interferon treatment delayed the evolution of the lymphoma but regression of tumour was not observed. The therapeutic effects observed with interferon in AKR mice compare favorably with reported results obtained using standard anti-cancer drugs.", "contents": "Interferon and murine leukemia. VII. Therapeutic effect of interferon preparations after diagnosis of lymphoma in AKR mice. Daily administration of potent mouse interferon preparations, begun after clinical diagnosis of lymphoma in AKR mice, increased average survival by approximately 100%. Interferon treatment delayed the evolution of the lymphoma but regression of tumour was not observed. The therapeutic effects observed with interferon in AKR mice compare favorably with reported results obtained using standard anti-cancer drugs."} {"id": "PMID:1270180", "title": "Modification of the effect of C. parvum on macrophage activity and tumour growth by X-irradiation.", "content": "The radiosensitivity of three forms of response to injection of C. parvum in mice has been investigated. The increase in phagocytin index evoked by IP or IV injection of 0.7 mg C. parvum (but not that evoked by 1.4 mg) was reduced but not abolished in mice given 350-500 rad whole-body irradiation 4 days before C. parvum injection. Irradiation (500-1,000 rad) 4 days after C. parvum injection had no such effect. The antitumour cytotoxicity in vitro of PE and spleen cells from C. parvum-treated mice was abolished by irradiation of the cell donor (400-800 rad) 4 days before C. parvum injection, but was not reduced by irradiation (800 rad) of the cell donor 4 days after C. parvum injection or of the effector cells in vitro. The antitumour response to systemic (IP) injection of C. parvum was reduced by 350-500 rad whole-body irradiation, irrespective of whether this was given 4 days before or 4 days after C. parvum injection. The response to intratumour injection of C. parvum was even more radiosensitive. It has been suggested in previous papers from this laboratory that the antitumour effect of C. parvum is related to its capacity to stimulate macrophage activity, although in addition T lymphocytes are necessary for local injection to be effective and non-T lymphocytes may be concerned in the response to both local and systemic injection. The present results in no way conflict with this view. They suggest in addition that the effect of C. parvum on the macrophage system is, to a considerable extent, due to stimulation of macrophage precursors to differentiate into actively phagocytic and cytotoxic mature cells.", "contents": "Modification of the effect of C. parvum on macrophage activity and tumour growth by X-irradiation. The radiosensitivity of three forms of response to injection of C. parvum in mice has been investigated. The increase in phagocytin index evoked by IP or IV injection of 0.7 mg C. parvum (but not that evoked by 1.4 mg) was reduced but not abolished in mice given 350-500 rad whole-body irradiation 4 days before C. parvum injection. Irradiation (500-1,000 rad) 4 days after C. parvum injection had no such effect. The antitumour cytotoxicity in vitro of PE and spleen cells from C. parvum-treated mice was abolished by irradiation of the cell donor (400-800 rad) 4 days before C. parvum injection, but was not reduced by irradiation (800 rad) of the cell donor 4 days after C. parvum injection or of the effector cells in vitro. The antitumour response to systemic (IP) injection of C. parvum was reduced by 350-500 rad whole-body irradiation, irrespective of whether this was given 4 days before or 4 days after C. parvum injection. The response to intratumour injection of C. parvum was even more radiosensitive. It has been suggested in previous papers from this laboratory that the antitumour effect of C. parvum is related to its capacity to stimulate macrophage activity, although in addition T lymphocytes are necessary for local injection to be effective and non-T lymphocytes may be concerned in the response to both local and systemic injection. The present results in no way conflict with this view. They suggest in addition that the effect of C. parvum on the macrophage system is, to a considerable extent, due to stimulation of macrophage precursors to differentiate into actively phagocytic and cytotoxic mature cells."} {"id": "PMID:1270181", "title": "The effect of BCG on extravascular mononuclear cell accumulation in vivo.", "content": "BCG injection produces an increased accumulation of adoptively transferred 51Cr-labelled mononuclear cells at the site of inflammatory reactions in rats by two mechanisms. Systemic immunization induced a population of \"activated\" cells which, compared with controls, had an increased life span in the circulation after transfer and migrated in increased numbers to a chemotactic stimulus. These cells also were found in significantly greater than normal levels in the liver. In addition, local injection of BCG selectively attracted adoptively transferred mononuclear cells. These mechanisms help to explain local mononuclear cell accumulation which accompanies tumor rejection following intralesional or systemic BCG immunization.", "contents": "The effect of BCG on extravascular mononuclear cell accumulation in vivo. BCG injection produces an increased accumulation of adoptively transferred 51Cr-labelled mononuclear cells at the site of inflammatory reactions in rats by two mechanisms. Systemic immunization induced a population of \"activated\" cells which, compared with controls, had an increased life span in the circulation after transfer and migrated in increased numbers to a chemotactic stimulus. These cells also were found in significantly greater than normal levels in the liver. In addition, local injection of BCG selectively attracted adoptively transferred mononuclear cells. These mechanisms help to explain local mononuclear cell accumulation which accompanies tumor rejection following intralesional or systemic BCG immunization."} {"id": "PMID:1270185", "title": "Studies on trypsin inhibitors. Part V. Synthesis of the protected octapeptide (sequence 36-43) of porcine pancreatic secretory trypsin inhibitor II (Kazal).", "content": "Synthesis is described of the partially protected octapeptide tert-butyloxycarbonyl-gamma-tert-butylglutamylasparaginyl-N-trifluoroacetyllysyl-N-trifluoracetyllysylarginyl-Ngamma-4,4'-dimethoxybenzhydryglutaminylthreonylproline corresponding to positions 36-43 of the amino acid sequence of porcine pancreatic secretory trypsin inhibitor II. The tetrapeptide free base arginyl-Ngamma-4,4'-dimethoxybenzhydrylglutaminylthreonylproline was acylated, by the azide proceedure, with the tripeptide benzyloxycarbonyl-asparaginyl-N-trifluoroacetyllsyl-N-trifluoroacetyllysine hydrazide. The resulting protected heptapeptide was partially deblocked by catalytic hydrogenation and reacted with alpha-1-succinimidyl-gamma-tert-butyl tert-butyloxycarbonylglutamate. The stereochemical homogeneity of the ensuing octapeptide was assessed, after partial deprotection with aqueous 90% trifluoroacetic acid, by digestion with papain and aminopeptidase M followed by quantitative amino acid analysis.", "contents": "Studies on trypsin inhibitors. Part V. Synthesis of the protected octapeptide (sequence 36-43) of porcine pancreatic secretory trypsin inhibitor II (Kazal). Synthesis is described of the partially protected octapeptide tert-butyloxycarbonyl-gamma-tert-butylglutamylasparaginyl-N-trifluoroacetyllysyl-N-trifluoracetyllysylarginyl-Ngamma-4,4'-dimethoxybenzhydryglutaminylthreonylproline corresponding to positions 36-43 of the amino acid sequence of porcine pancreatic secretory trypsin inhibitor II. The tetrapeptide free base arginyl-Ngamma-4,4'-dimethoxybenzhydrylglutaminylthreonylproline was acylated, by the azide proceedure, with the tripeptide benzyloxycarbonyl-asparaginyl-N-trifluoroacetyllsyl-N-trifluoroacetyllysine hydrazide. The resulting protected heptapeptide was partially deblocked by catalytic hydrogenation and reacted with alpha-1-succinimidyl-gamma-tert-butyl tert-butyloxycarbonylglutamate. The stereochemical homogeneity of the ensuing octapeptide was assessed, after partial deprotection with aqueous 90% trifluoroacetic acid, by digestion with papain and aminopeptidase M followed by quantitative amino acid analysis."} {"id": "PMID:1270186", "title": "Studies on trypsin inhibitors. Part VI. Synthesis of the protected nonapeptide (sequence 44-52) of porcine pancreatic secretory trypsin inhibitor II (Kazal).", "content": "Synthesis is described of the partially protected nonapeptide tert-butyloxycarbonyl-valylleucylisoleucylglutaminyl-N-trifluoroacetyllsylserylglycylprolyl-S-acetamido-methylcysteine corresponding to positions 44-52 of the amino acid sequence of porcine pancreatic secretory trypsin inhibitor II. The hexapeptide free base glutaminyl-N-trifluoroacetyllsylserylglycylprolyl-S-acetamidomethylcysteine, prepared by two alternative routes, was acylated by the azide procedure, with the tripeptide tert-butyloxycarbonylvalylleucylisoleucine hydrazide. The stereochemical homogeneity of the resulting nonapeptide was assessed, after partial deprotection by treatment with aqueous 90% trifluoroacetic acid, by digestion with papain and aminopeptidase M followed by quantitative amino acid analysis.", "contents": "Studies on trypsin inhibitors. Part VI. Synthesis of the protected nonapeptide (sequence 44-52) of porcine pancreatic secretory trypsin inhibitor II (Kazal). Synthesis is described of the partially protected nonapeptide tert-butyloxycarbonyl-valylleucylisoleucylglutaminyl-N-trifluoroacetyllsylserylglycylprolyl-S-acetamido-methylcysteine corresponding to positions 44-52 of the amino acid sequence of porcine pancreatic secretory trypsin inhibitor II. The hexapeptide free base glutaminyl-N-trifluoroacetyllsylserylglycylprolyl-S-acetamidomethylcysteine, prepared by two alternative routes, was acylated by the azide procedure, with the tripeptide tert-butyloxycarbonylvalylleucylisoleucine hydrazide. The stereochemical homogeneity of the resulting nonapeptide was assessed, after partial deprotection by treatment with aqueous 90% trifluoroacetic acid, by digestion with papain and aminopeptidase M followed by quantitative amino acid analysis."} {"id": "PMID:1270187", "title": "Non-random relationships among amino acids in protein sequences.", "content": "We have computed the observed distribution of amino acid pairs n, n+1 up to n, n+10 within 100 unrelated protein sequences containing a total of 14,034 amino acids. The expected distribution of the same amino acid pairs was calculated assuming that the amino acids within each sequence are arranged in random order. Statistical analysis of the data shows that amino acids in the n, n+1 and n, n+3 relationship deviate from random expectation at the 1% level of significance. These relationships are consistent with known secondary structures; however, there are no amino acid pairs which obviously contribute to the non-random result.", "contents": "Non-random relationships among amino acids in protein sequences. We have computed the observed distribution of amino acid pairs n, n+1 up to n, n+10 within 100 unrelated protein sequences containing a total of 14,034 amino acids. The expected distribution of the same amino acid pairs was calculated assuming that the amino acids within each sequence are arranged in random order. Statistical analysis of the data shows that amino acids in the n, n+1 and n, n+3 relationship deviate from random expectation at the 1% level of significance. These relationships are consistent with known secondary structures; however, there are no amino acid pairs which obviously contribute to the non-random result."} {"id": "PMID:1270188", "title": "On the reaction of acetamidomethanol with native and reduced bovine pancreatic trypsin inhibtor (Kunitz inhibitor).", "content": "The stability of native and reduced bovine pancreatic trypsin inhibitor (Kunitz inhibitor) in anhydrous hydrogen fluoride and their reaction with acetamidomethanol, in the same solvent, have been investigated. The bovine Kunitz inhibitor appears to be stable in liquid hydrogen fluoride but the reduced molecule loses about 50% of its ability to regain inhibitory power, upon air oxidation, by exposure to this solvent. Tyrosine residues appear to be affected by acetamidomethylation of the native protein to give a modified inhibitor which is still highly active in inhibiting trypsin. The extent of correct refolding, upon reoxidation, of the reduced tyrosine modified-inhibitor is greatly diminished. Tyrosine modification can be prevented by carrying out the acetamidomethylation reaction in the presence of excess anisole. The stability constants and the standard free energies of binding of the complexes between trypsin and the native and the tyrosine modified-inhibitor have been determined.", "contents": "On the reaction of acetamidomethanol with native and reduced bovine pancreatic trypsin inhibtor (Kunitz inhibitor). The stability of native and reduced bovine pancreatic trypsin inhibitor (Kunitz inhibitor) in anhydrous hydrogen fluoride and their reaction with acetamidomethanol, in the same solvent, have been investigated. The bovine Kunitz inhibitor appears to be stable in liquid hydrogen fluoride but the reduced molecule loses about 50% of its ability to regain inhibitory power, upon air oxidation, by exposure to this solvent. Tyrosine residues appear to be affected by acetamidomethylation of the native protein to give a modified inhibitor which is still highly active in inhibiting trypsin. The extent of correct refolding, upon reoxidation, of the reduced tyrosine modified-inhibitor is greatly diminished. Tyrosine modification can be prevented by carrying out the acetamidomethylation reaction in the presence of excess anisole. The stability constants and the standard free energies of binding of the complexes between trypsin and the native and the tyrosine modified-inhibitor have been determined."} {"id": "PMID:1270189", "title": "Purification of a lysinonorleucine cross-linked peptide fraction from porcine aorta elastin.", "content": "Highly purified elastin from porcine aorta was submitted to elastase digestion. The enzymic products were subjected to gel filtration on Sephadex G 25. The excluded fraction was then submitted to thermolysin digestion and gel filtration. The excluded fraction was submitted to partial acid hydrolysis and gel filtration. Several sub-fractions were obtained. The F3 subfraction containing cross-linking agents (desmosines and lysinonorleucine) was finally subjected to ion exchange chromatography. A highly enriched peptide fraction containing lysinomorleucine was obtained and then purified by preparative electrophoresis. The ratio of enrichment passed from 2 residues of lysinonorleucine (expressed as lysine) from starting material (elastin) to 178 out of 1,000 residues in the final step. In this peptide fraction, if we express in molar ratio and consider the amount of lysinonorleucine is one residue, the following amino-acid composition is Pro:3, Gly:1, Ala:2, LNL:1, Lys:2. No traces of desmosines are detected. The role of lysinonorleucine in bridging functions in elastin is discussed.", "contents": "Purification of a lysinonorleucine cross-linked peptide fraction from porcine aorta elastin. Highly purified elastin from porcine aorta was submitted to elastase digestion. The enzymic products were subjected to gel filtration on Sephadex G 25. The excluded fraction was then submitted to thermolysin digestion and gel filtration. The excluded fraction was submitted to partial acid hydrolysis and gel filtration. Several sub-fractions were obtained. The F3 subfraction containing cross-linking agents (desmosines and lysinonorleucine) was finally subjected to ion exchange chromatography. A highly enriched peptide fraction containing lysinomorleucine was obtained and then purified by preparative electrophoresis. The ratio of enrichment passed from 2 residues of lysinonorleucine (expressed as lysine) from starting material (elastin) to 178 out of 1,000 residues in the final step. In this peptide fraction, if we express in molar ratio and consider the amount of lysinonorleucine is one residue, the following amino-acid composition is Pro:3, Gly:1, Ala:2, LNL:1, Lys:2. No traces of desmosines are detected. The role of lysinonorleucine in bridging functions in elastin is discussed."} {"id": "PMID:1270190", "title": "Circular dichroism of human pituitary luteinizing hormone and its glycopeptides. Curve resolution and band assignments to the peptide chromophore, aromatic residues, disulfides, and N-acetylated amino sugars.", "content": "The circular dichroic (CS) spectrum of the glycoprotein hormone, human pituitary luteinizing hormone (hLH), has been determined between 195-320 nm and resolved into gaussian constituents. Below 230 nm the CD spectrum is characterized by a negative extremum at 207 nm with a shoulder at 217 nm. Resolution into gaussian constituents of the 200-230 nm CD spectrum resulted in two resolved negative bands, one at 206 nm and the other at 215 nm. The latter band is assigned to beta-structure which is estimated to be about 25%. The 206 nm resolved band is assigned to the N-acetylated carbohydrate groups (e.g. N-acetyl glucosamine, galactosamine, and neuraminic acid). This is based partly on the evidence that the CD spectrum of the hLH glycopeptide fraction (prepared by a pronase digestion of s-carboxymethylated hLH) exhibited a negative extremum at 207.5 nm, which is close to the resolved 206 nm band in hLH. Above 230 nm the CD spectrum is characterized by a negative extremum at about 275 nm. Most of the ellipticity in this region is attributed to the disulfides in hLH. Both strong acid (0.1 N hcl) and concentrated guanidine hydrochloride (4 M) affect the ellipticity in the vicinity of 275 nm, but only the latter (as well as concentrated urea) has a major effect on the CD spectrum below 230 nm indicating extensive conformational changes. There is, however, some loss of beta-structure in 0.1 N hcl. Thus, it appears that the conformation of the hLH subunits in these subunit-dissociating agents is rather different. There was no dramatic change in the magnitude of the 207 nm extremum of native hLH between 10-50C.", "contents": "Circular dichroism of human pituitary luteinizing hormone and its glycopeptides. Curve resolution and band assignments to the peptide chromophore, aromatic residues, disulfides, and N-acetylated amino sugars. The circular dichroic (CS) spectrum of the glycoprotein hormone, human pituitary luteinizing hormone (hLH), has been determined between 195-320 nm and resolved into gaussian constituents. Below 230 nm the CD spectrum is characterized by a negative extremum at 207 nm with a shoulder at 217 nm. Resolution into gaussian constituents of the 200-230 nm CD spectrum resulted in two resolved negative bands, one at 206 nm and the other at 215 nm. The latter band is assigned to beta-structure which is estimated to be about 25%. The 206 nm resolved band is assigned to the N-acetylated carbohydrate groups (e.g. N-acetyl glucosamine, galactosamine, and neuraminic acid). This is based partly on the evidence that the CD spectrum of the hLH glycopeptide fraction (prepared by a pronase digestion of s-carboxymethylated hLH) exhibited a negative extremum at 207.5 nm, which is close to the resolved 206 nm band in hLH. Above 230 nm the CD spectrum is characterized by a negative extremum at about 275 nm. Most of the ellipticity in this region is attributed to the disulfides in hLH. Both strong acid (0.1 N hcl) and concentrated guanidine hydrochloride (4 M) affect the ellipticity in the vicinity of 275 nm, but only the latter (as well as concentrated urea) has a major effect on the CD spectrum below 230 nm indicating extensive conformational changes. There is, however, some loss of beta-structure in 0.1 N hcl. Thus, it appears that the conformation of the hLH subunits in these subunit-dissociating agents is rather different. There was no dramatic change in the magnitude of the 207 nm extremum of native hLH between 10-50C."} {"id": "PMID:1270191", "title": "Solid phase synthesis and some pharmacological properties of 8-D-homoarginine-vasopressin and 1-deamino-8-D-homoarginine-vasopressin.", "content": "Fully protected 8-D-lysine-vasopresin and 1-deamino-8-D-lysine-vasopressin were synthesized by the solid phase method. Selective removal of the lysine protection and reaction with 1-guanyl-3,5-dimethylpyrazole converted D-lysine into D-homoarginine. The title compounds were then obtained by treatment with sodium in liquid ammonia and oxidation in dilute aqueous solution. Although the antidiuretic activities are lower than for the corresponding D-argining derivatives, the even lower pressor effects make the new analogues highly specific antidiuretic agents. The A/P ratios for 8-D-homoarginine-vasopressin and its 1-deamino derivative are 100 and 3,300, respectively.", "contents": "Solid phase synthesis and some pharmacological properties of 8-D-homoarginine-vasopressin and 1-deamino-8-D-homoarginine-vasopressin. Fully protected 8-D-lysine-vasopresin and 1-deamino-8-D-lysine-vasopressin were synthesized by the solid phase method. Selective removal of the lysine protection and reaction with 1-guanyl-3,5-dimethylpyrazole converted D-lysine into D-homoarginine. The title compounds were then obtained by treatment with sodium in liquid ammonia and oxidation in dilute aqueous solution. Although the antidiuretic activities are lower than for the corresponding D-argining derivatives, the even lower pressor effects make the new analogues highly specific antidiuretic agents. The A/P ratios for 8-D-homoarginine-vasopressin and its 1-deamino derivative are 100 and 3,300, respectively."} {"id": "PMID:1270192", "title": "Preparation of chromophoric substrates for the glutamoyl specific staphylococcal protease.", "content": "The synthesis of chromophoric substrates allowing an accurate determination of the staphylococcal protease activity is described. BOC-L-Glu-OPh, BOC-L-Phe-L-Glu-OPh, BOC-L-Ala-L-Glu-OPh, BOC-L-Ser-L-Glu-OPh and Z-L-Glu-pNA were prepared. Kinetic parameters of the staphyloccal protease-catalysed hydrolyses of these substrates are compared. In every case the dipeptide ester substrates lead to a lower catalytic efficiency (kcat/Km ratio), compared with either BOC-L-Glu-OPh or Z-L-Glu-OPh, mainly because of an increase in the Km value. Like other serine proteinases, the staphylococcal protease exhibits a high ratio of eeterase to peptidase activity, the kcat/Km ratio being 2.6 X 10(5)-fold higher with the Z-L-Glu-OPh than with the Z-L-Glu-pNA.", "contents": "Preparation of chromophoric substrates for the glutamoyl specific staphylococcal protease. The synthesis of chromophoric substrates allowing an accurate determination of the staphylococcal protease activity is described. BOC-L-Glu-OPh, BOC-L-Phe-L-Glu-OPh, BOC-L-Ala-L-Glu-OPh, BOC-L-Ser-L-Glu-OPh and Z-L-Glu-pNA were prepared. Kinetic parameters of the staphyloccal protease-catalysed hydrolyses of these substrates are compared. In every case the dipeptide ester substrates lead to a lower catalytic efficiency (kcat/Km ratio), compared with either BOC-L-Glu-OPh or Z-L-Glu-OPh, mainly because of an increase in the Km value. Like other serine proteinases, the staphylococcal protease exhibits a high ratio of eeterase to peptidase activity, the kcat/Km ratio being 2.6 X 10(5)-fold higher with the Z-L-Glu-OPh than with the Z-L-Glu-pNA."} {"id": "PMID:1270193", "title": "Studies on pituitary lactogenic hormone. The primary structure of the porcine hormone.", "content": "The complete amino acid sequence of porcine lactogenic hormone has been elucidated. It consists of 199 amino acid residues with three disulfide bridges formed by residues 4-11, 58-174, and 191-199. The two tryptophan residues are in positions 91 and 150. A high degree of homology exists between the known structure of ovine prolactin and the porcine lactogenic hormone. This led to a re-examination of residues 82-90 in the ovine prolactin structure, where an extra leucine was found in position 88.", "contents": "Studies on pituitary lactogenic hormone. The primary structure of the porcine hormone. The complete amino acid sequence of porcine lactogenic hormone has been elucidated. It consists of 199 amino acid residues with three disulfide bridges formed by residues 4-11, 58-174, and 191-199. The two tryptophan residues are in positions 91 and 150. A high degree of homology exists between the known structure of ovine prolactin and the porcine lactogenic hormone. This led to a re-examination of residues 82-90 in the ovine prolactin structure, where an extra leucine was found in position 88."} {"id": "PMID:1270194", "title": "Studies on trypsin inhibitors. Part IV, Synthesis of the protected undecapeptide (sequence 25-35) of porcine pancreatic secretory trypsin inhibitor II (Kazal).", "content": "Synthesis is described of the protected undecapeptide tert-butyloxycarbonylisoleucyl-threonyltyrosylserylasparaginyl-gamma-tert-butylglutamyl-S-acetamidomethylcysteinyl-valylleucyl-S-acetamidomethylcysteinylseriny hydrazide corresponding to positions 25-35 of the amino acid sequence of porcine pancreatic secretory trypsin inhibitor II (Kazal). The hepatapeptide free base methyl asparaginyl-gamma-tert-butylglutamyl-S-acetamidomethylcysteinylvalylleucyl-S-acetamidomethylcysteinylserinate (sequency 29-35) was acylated, by the azide procedure, with the tetrapeptide tert-butyloxycarbonl-isoleucylthreonyltyrosylserine hydrazide /sequence 25-28) and the resulting tert-butyloxycarbonylundecapeptide methyl ester was transformed into the corresponding hydrazide by hydrazinolysis. The stereochemical homogeneity of the final product was assessed, after partial deprotection with aqueous 90% trifuoroacetic acid, by digestion with papain and aminopeptidase M followed by quantitative amino acid analysis.", "contents": "Studies on trypsin inhibitors. Part IV, Synthesis of the protected undecapeptide (sequence 25-35) of porcine pancreatic secretory trypsin inhibitor II (Kazal). Synthesis is described of the protected undecapeptide tert-butyloxycarbonylisoleucyl-threonyltyrosylserylasparaginyl-gamma-tert-butylglutamyl-S-acetamidomethylcysteinyl-valylleucyl-S-acetamidomethylcysteinylseriny hydrazide corresponding to positions 25-35 of the amino acid sequence of porcine pancreatic secretory trypsin inhibitor II (Kazal). The hepatapeptide free base methyl asparaginyl-gamma-tert-butylglutamyl-S-acetamidomethylcysteinylvalylleucyl-S-acetamidomethylcysteinylserinate (sequency 29-35) was acylated, by the azide procedure, with the tetrapeptide tert-butyloxycarbonl-isoleucylthreonyltyrosylserine hydrazide /sequence 25-28) and the resulting tert-butyloxycarbonylundecapeptide methyl ester was transformed into the corresponding hydrazide by hydrazinolysis. The stereochemical homogeneity of the final product was assessed, after partial deprotection with aqueous 90% trifuoroacetic acid, by digestion with papain and aminopeptidase M followed by quantitative amino acid analysis."} {"id": "PMID:1270195", "title": "High tibial osteotomy for osteoarthritis of the knee: a changing concept.", "content": "High tibial osteotomy is most successful in patients with osteoarthritis with mild varus deformity which is not associated with subluxation of flexion contracture. Success in the valgus knee is limited. If tibial osteotomy is indicated, undercorrection is undesirable in the varus knee while overcorrection is undesirable in the valgus knee.", "contents": "High tibial osteotomy for osteoarthritis of the knee: a changing concept. High tibial osteotomy is most successful in patients with osteoarthritis with mild varus deformity which is not associated with subluxation of flexion contracture. Success in the valgus knee is limited. If tibial osteotomy is indicated, undercorrection is undesirable in the varus knee while overcorrection is undesirable in the valgus knee."} {"id": "PMID:1270196", "title": "Subcutaneous rupture of the Achilles tendon.", "content": "A series of 27 ruptures of the tendo Achillis are reported. Samples of tendon tissue, taken both at the site of rupture and at a distance from it, were histologically examined. Four different surgical procedures were performed. All patients showed marked degenerative changes of the tendon tissue. No definite relationship was found between the surgical procedure employed and functional results obtained. These were rated as excellent in 12 cases, good in 11 and fair in four. Only minor complications attending the operation occurred. We emphasize the superiority of open repair over conservative treatment.", "contents": "Subcutaneous rupture of the Achilles tendon. A series of 27 ruptures of the tendo Achillis are reported. Samples of tendon tissue, taken both at the site of rupture and at a distance from it, were histologically examined. Four different surgical procedures were performed. All patients showed marked degenerative changes of the tendon tissue. No definite relationship was found between the surgical procedure employed and functional results obtained. These were rated as excellent in 12 cases, good in 11 and fair in four. Only minor complications attending the operation occurred. We emphasize the superiority of open repair over conservative treatment."} {"id": "PMID:1270197", "title": "Fatal fat embolism associated with polymethyl methacrylate bone cement.", "content": "Three fatalities after procedures involving the use of polymethyl methacrylate cement are reported. Autopsy studies showed varying degrees of pulmonary fat embolism although lack of correction of operative blood loss was the major factor.", "contents": "Fatal fat embolism associated with polymethyl methacrylate bone cement. Three fatalities after procedures involving the use of polymethyl methacrylate cement are reported. Autopsy studies showed varying degrees of pulmonary fat embolism although lack of correction of operative blood loss was the major factor."} {"id": "PMID:1270198", "title": "Use of acrylic of low polymerization after heminandibulectomy.", "content": "Two cases of mandibular reconstruction are presented in which a premolded prosthesis of acrylic of low polymerization covered by silicone rubber was used. We believe that the good results obtained were not only due to the material used, but also because the periosteum and meniscus were preserved in the joint space.", "contents": "Use of acrylic of low polymerization after heminandibulectomy. Two cases of mandibular reconstruction are presented in which a premolded prosthesis of acrylic of low polymerization covered by silicone rubber was used. We believe that the good results obtained were not only due to the material used, but also because the periosteum and meniscus were preserved in the joint space."} {"id": "PMID:1270199", "title": "Temporomandibular ankylosis.", "content": "1. Intraarticular hydrocortisone and passive manipulation under general anesthesia does not help mobilize the jaw. 2. Condylectomy gives good results in selected cases, where the duration of ankylosis is minimal. 3. Longer duration requires wide excision of the condyloid as well as coronoid processes. The opposite side also must be operated on in most late cases. A gap of more than 2 cm is left in order to avoid recurrences. 4. Postoperative physiotherapy of the jaw in the form of active and resistive movements of the jaw, if started early, gives good functional results and helps recover the function of the chewing muscles. 5. Functional results are good even without interposition of soft tissues or use of prostheses. 6. Skeletal traction after operation is unnecessary. 7. The results of adequate resection of bone followed by early and adequate physiotherapy are very gratifying to the patient.", "contents": "Temporomandibular ankylosis. 1. Intraarticular hydrocortisone and passive manipulation under general anesthesia does not help mobilize the jaw. 2. Condylectomy gives good results in selected cases, where the duration of ankylosis is minimal. 3. Longer duration requires wide excision of the condyloid as well as coronoid processes. The opposite side also must be operated on in most late cases. A gap of more than 2 cm is left in order to avoid recurrences. 4. Postoperative physiotherapy of the jaw in the form of active and resistive movements of the jaw, if started early, gives good functional results and helps recover the function of the chewing muscles. 5. Functional results are good even without interposition of soft tissues or use of prostheses. 6. Skeletal traction after operation is unnecessary. 7. The results of adequate resection of bone followed by early and adequate physiotherapy are very gratifying to the patient."} {"id": "PMID:1270201", "title": "Congenital dysplasia of the hip in northern India.", "content": "The incidence of congenital dysplasia of the hip in Northern India is 0.8% in infants born in two hospital maternity units which are interested in detecting this condition.", "contents": "Congenital dysplasia of the hip in northern India. The incidence of congenital dysplasia of the hip in Northern India is 0.8% in infants born in two hospital maternity units which are interested in detecting this condition."} {"id": "PMID:1270203", "title": "Fatigue fracture of the femoral neck.", "content": "Fatigue fractures in the necks of femurs removed from fresh cadavers were produced experimentally by applying repeated compression and rotational stresses. We found that a load applied once in a physiological direction may be within the ultimate strength of the bone, but may produce a fracture if applied repeatedly. With increased age, chances of fatigue failure increased age, chances of fatigue failure increased and loads of even physiological magnitude produced fatigue fractures. This may also happen during life. The subcapital fractures produced in these specimens were similar to those seen in patients in a clinical practice. This has been reported many times in new young military recruits. In individuals undergoing unusually strenuous exercises, the stress concentrations can be unusually high.", "contents": "Fatigue fracture of the femoral neck. Fatigue fractures in the necks of femurs removed from fresh cadavers were produced experimentally by applying repeated compression and rotational stresses. We found that a load applied once in a physiological direction may be within the ultimate strength of the bone, but may produce a fracture if applied repeatedly. With increased age, chances of fatigue failure increased age, chances of fatigue failure increased and loads of even physiological magnitude produced fatigue fractures. This may also happen during life. The subcapital fractures produced in these specimens were similar to those seen in patients in a clinical practice. This has been reported many times in new young military recruits. In individuals undergoing unusually strenuous exercises, the stress concentrations can be unusually high."} {"id": "PMID:1270204", "title": "Intravenous infusion anesthesia for upper extremity surgery.", "content": "Regional anesthesia by intravenous infusion was successfully performed in 126 cases with only three complications. The technic is particularly useful for outpatient surgery and for cases where general anesthesia is unsuitable. This type of anesthesia is not for routine use. Proper equipment and personnel must be available. We do not recommend its usage in very obese patients or where absolute hemostasis is essential. Caution is urged in cases where edema has developed as the absorbtion of local anesthetic is not predictable.", "contents": "Intravenous infusion anesthesia for upper extremity surgery. Regional anesthesia by intravenous infusion was successfully performed in 126 cases with only three complications. The technic is particularly useful for outpatient surgery and for cases where general anesthesia is unsuitable. This type of anesthesia is not for routine use. Proper equipment and personnel must be available. We do not recommend its usage in very obese patients or where absolute hemostasis is essential. Caution is urged in cases where edema has developed as the absorbtion of local anesthetic is not predictable."} {"id": "PMID:1270205", "title": "Unusual lesions of the patella.", "content": "We have reported 13 cases illustrating various rare lesions of the patells and discussed the incidence and treatment and reviewed other reported cases of each type of lesion.", "contents": "Unusual lesions of the patella. We have reported 13 cases illustrating various rare lesions of the patells and discussed the incidence and treatment and reviewed other reported cases of each type of lesion."} {"id": "PMID:1270209", "title": "Complementary retroperitoneal lavage.", "content": "Surgery is required in acute necrotic pancreatitis when ominous signs appear after three days of intensive medical therapy. The surgical procedure is outlined and retroperitoneal lavage is proposed as a necessary complement. A protocol for this procedure is given. We believe that removal of necrotic tissue is not synonymous with partial pancreatectomy. Lavage completes what we consider \"lesional pancreatic surgery\" by diluting, buffering and washing out residual caustic tissues. The resulting fistula is directed and spontaneously dries up in most cases.", "contents": "Complementary retroperitoneal lavage. Surgery is required in acute necrotic pancreatitis when ominous signs appear after three days of intensive medical therapy. The surgical procedure is outlined and retroperitoneal lavage is proposed as a necessary complement. A protocol for this procedure is given. We believe that removal of necrotic tissue is not synonymous with partial pancreatectomy. Lavage completes what we consider \"lesional pancreatic surgery\" by diluting, buffering and washing out residual caustic tissues. The resulting fistula is directed and spontaneously dries up in most cases."} {"id": "PMID:1270211", "title": "Unusual lesions of the clavicle.", "content": "Eight types of rare clavicular lesions comprising 41 cases with their treatment and results are presented. Total claviclectomy was performed in ten cases of pyogenic osteomyelitis with no resultant functional disability to the patient. We advocate this as the treatment of choice.", "contents": "Unusual lesions of the clavicle. Eight types of rare clavicular lesions comprising 41 cases with their treatment and results are presented. Total claviclectomy was performed in ten cases of pyogenic osteomyelitis with no resultant functional disability to the patient. We advocate this as the treatment of choice."} {"id": "PMID:1270212", "title": "Lumbar sympathectomy in the treatment of uncomplicated intermittent claudication.", "content": "The precise role lumbar sympathectomy plays in the treatment of uncomplicated intermittent claudication continues to be debated. Past experience at this institution indicates that lumbar sympathectomy has a definite positive role in uncomplicated intermittent claudication. A critical analysis of the 86 patients included in this study adds further support to this contention. Properly selected patients who undergo complete anatomic sympathetic denervation of the lower limbs continue to have very satisfactory results, as they have since 1947 in this institution.", "contents": "Lumbar sympathectomy in the treatment of uncomplicated intermittent claudication. The precise role lumbar sympathectomy plays in the treatment of uncomplicated intermittent claudication continues to be debated. Past experience at this institution indicates that lumbar sympathectomy has a definite positive role in uncomplicated intermittent claudication. A critical analysis of the 86 patients included in this study adds further support to this contention. Properly selected patients who undergo complete anatomic sympathetic denervation of the lower limbs continue to have very satisfactory results, as they have since 1947 in this institution."} {"id": "PMID:1270217", "title": "Modified pancreatoduodenectomy for carcinoma of the head of the pancreas: preliminary report.", "content": "A new technic for restoration of gastrointestinal continuity following pancreatoduodenectomy for cinoma of the head of the pancreas is described and the advantages discussed. We believe this method prevents any leakage of the anastomosis and reduces mortality and morbidity because of better drainage. Also, by avoiding stasis, infection, which is a common complication in this kind of surgery, is prevented.", "contents": "Modified pancreatoduodenectomy for carcinoma of the head of the pancreas: preliminary report. A new technic for restoration of gastrointestinal continuity following pancreatoduodenectomy for cinoma of the head of the pancreas is described and the advantages discussed. We believe this method prevents any leakage of the anastomosis and reduces mortality and morbidity because of better drainage. Also, by avoiding stasis, infection, which is a common complication in this kind of surgery, is prevented."} {"id": "PMID:1270218", "title": "Clinical and therapeutic applications of a new pathogenetic theory on the dumping syndrome.", "content": "Based on experimental and clinical studies we have deduced the existence of a neuro-osmotic dumping syndrome and a truly osmotic dumping syndrome that differ in pathogenesis and clinical symptoms.", "contents": "Clinical and therapeutic applications of a new pathogenetic theory on the dumping syndrome. Based on experimental and clinical studies we have deduced the existence of a neuro-osmotic dumping syndrome and a truly osmotic dumping syndrome that differ in pathogenesis and clinical symptoms."} {"id": "PMID:1270222", "title": "Intestinal parasitic infestation among parturients in Trinidad and Tobago.", "content": "1. In this limited survey, 42.5% of parturients were found to be infested with intestinal parasites. 2. Hookworm, Trichuris and Entamoeba infestations were the most common. 3. Race, social class and locality influenced in the incidence of the different types of infestations. 4. Those infested with hookworm had longer labor, smaller babies and higher incidence of prematurity.", "contents": "Intestinal parasitic infestation among parturients in Trinidad and Tobago. 1. In this limited survey, 42.5% of parturients were found to be infested with intestinal parasites. 2. Hookworm, Trichuris and Entamoeba infestations were the most common. 3. Race, social class and locality influenced in the incidence of the different types of infestations. 4. Those infested with hookworm had longer labor, smaller babies and higher incidence of prematurity."} {"id": "PMID:1270226", "title": "Intussusception in adults.", "content": "A review of intussusception in adults treated over a 12-year period is presented. In most cases intussusception was ileocolic in type and symptoms were nonspecific. Benign neoplasms and idiopathic causes were more prevalent in small bowel cases while malignant neoplasms were more common when the colon was involved. In 38% of the cases, no obvious cause for the intussusception was found. All cases were treated surgically, usually by reduction or resection or both.", "contents": "Intussusception in adults. A review of intussusception in adults treated over a 12-year period is presented. In most cases intussusception was ileocolic in type and symptoms were nonspecific. Benign neoplasms and idiopathic causes were more prevalent in small bowel cases while malignant neoplasms were more common when the colon was involved. In 38% of the cases, no obvious cause for the intussusception was found. All cases were treated surgically, usually by reduction or resection or both."} {"id": "PMID:1270227", "title": "Primary liposarcoma of the skull.", "content": "Only 14 cases of primary liposarcoma of bones have been reported in the available world literature. This is the first report of its origin from the calvaria. The tumor showed excellent response to deep x-ray therapy.", "contents": "Primary liposarcoma of the skull. Only 14 cases of primary liposarcoma of bones have been reported in the available world literature. This is the first report of its origin from the calvaria. The tumor showed excellent response to deep x-ray therapy."} {"id": "PMID:1270230", "title": "Pattern of intestinal obstruction in Khartoum.", "content": "We operated on 138 patients for intestinal obstruction. The different causes are discussed and their pattern of occurrence is compared with that reported from England and other African countries. The 27.6% mortality rate was closely associated with the 28.2% incidence of gangrene. Factors which may lower this high mortality rate are enumerated.", "contents": "Pattern of intestinal obstruction in Khartoum. We operated on 138 patients for intestinal obstruction. The different causes are discussed and their pattern of occurrence is compared with that reported from England and other African countries. The 27.6% mortality rate was closely associated with the 28.2% incidence of gangrene. Factors which may lower this high mortality rate are enumerated."} {"id": "PMID:1270232", "title": "Kidney stone matrix. Differences in acidic protein composition.", "content": "Organic matrices from kidney stones of several mineral compositions (calcium oxalate, uric acid, and apatite-struvite) were isolated and found to contain an abundance of acidic amino acids. The calcium oxalate stones contained 50% aspartic and glutamic acid residues while the uric acid stones contained over 65%. The apatite-struvite stones had only 30% of these two amino acid residues and also contained 20% glycine residues. Since the specific amino acid composition differed for stones of different mineral content, it was felt that the organic matrix might play the role of a nucleating agent.", "contents": "Kidney stone matrix. Differences in acidic protein composition. Organic matrices from kidney stones of several mineral compositions (calcium oxalate, uric acid, and apatite-struvite) were isolated and found to contain an abundance of acidic amino acids. The calcium oxalate stones contained 50% aspartic and glutamic acid residues while the uric acid stones contained over 65%. The apatite-struvite stones had only 30% of these two amino acid residues and also contained 20% glycine residues. Since the specific amino acid composition differed for stones of different mineral content, it was felt that the organic matrix might play the role of a nucleating agent."} {"id": "PMID:1270233", "title": "Long term tissue responses to catgut and collagen sutures.", "content": "Reaction of catgut and collagen sutures in both wounded and nonwounded bladder, kidney, muscle, and liver tissue was studied in guinea pigs up to 130 days after implantation. A minimal amount of degradation of ths so-called absorbable sutures was observed. There was little difference in absorption rates in the tissues studied although there seemed to be slightly greater absorption in the kidney than in other tissues. Tissue responses were characterized by the formation of a bilaminar connective tissue capsule. The inner zone contained primarily fibroblasts and histiocytes, while lymphocytes, neutrophils, and eosinophils were scattered throughout both layers. Multinucleated giant cells were often observed in the inner layer, and aggregates of lymphocytes and mast cells were occasionally found in the pericapsular areas. Calculi formed on those suture loops that were loosely tied and thus projected into the bladder lumen.", "contents": "Long term tissue responses to catgut and collagen sutures. Reaction of catgut and collagen sutures in both wounded and nonwounded bladder, kidney, muscle, and liver tissue was studied in guinea pigs up to 130 days after implantation. A minimal amount of degradation of ths so-called absorbable sutures was observed. There was little difference in absorption rates in the tissues studied although there seemed to be slightly greater absorption in the kidney than in other tissues. Tissue responses were characterized by the formation of a bilaminar connective tissue capsule. The inner zone contained primarily fibroblasts and histiocytes, while lymphocytes, neutrophils, and eosinophils were scattered throughout both layers. Multinucleated giant cells were often observed in the inner layer, and aggregates of lymphocytes and mast cells were occasionally found in the pericapsular areas. Calculi formed on those suture loops that were loosely tied and thus projected into the bladder lumen."} {"id": "PMID:1270234", "title": "Investigation of urine transport in the ureter of the pig by x-ray videodensitometry. I. The effect of increasing diuresis on velocity and rhythm of contractions: relationship between pressure wave and urine bolus.", "content": "The flow rate is the decisive parameter of ureteric function. The frequency and the velocity of the contraction waves can be measured by X-ray videodensitometry without having to touch the ureter. The relationship between flow rate (milliliters per minute) and wave velocity (millimeters per second) is investigated in the pig ureter. It can be demonstrated that the wave velocity is a quadratic function of the perfusion. The graphic representation of this function corresponds ot a parabolic curve. The relationship between the bolus and the pressure wave is analyzed and it is shown that the time lag between the rear end of the bolus and the pressure peak is independent of the wave velocity. The theoretical ureter model of Weinberg is experimentally confirmed by simultaneous manometry and videodensitometry.", "contents": "Investigation of urine transport in the ureter of the pig by x-ray videodensitometry. I. The effect of increasing diuresis on velocity and rhythm of contractions: relationship between pressure wave and urine bolus. The flow rate is the decisive parameter of ureteric function. The frequency and the velocity of the contraction waves can be measured by X-ray videodensitometry without having to touch the ureter. The relationship between flow rate (milliliters per minute) and wave velocity (millimeters per second) is investigated in the pig ureter. It can be demonstrated that the wave velocity is a quadratic function of the perfusion. The graphic representation of this function corresponds ot a parabolic curve. The relationship between the bolus and the pressure wave is analyzed and it is shown that the time lag between the rear end of the bolus and the pressure peak is independent of the wave velocity. The theoretical ureter model of Weinberg is experimentally confirmed by simultaneous manometry and videodensitometry."} {"id": "PMID:1270235", "title": "Investigation of urine transport in the ureter of the pig by x-ray videodensitometry. II. The effect of an increasing obstruction on velocity, rhythm, and efficiency of the contraction waves.", "content": "The effect on an increasing acute obstruction on the motility of the ureter was analyzed by means of X-ray videodensitometry. The mean wave velocity decreases and the efficiency of the individual contraction is reduced. The lumen of the ureter is no longer closed completely and an increasing fraction of the urine bolus flows backward. The regurgitation can be seen cineradiographically and assessed semiquantitatively by densitometry.", "contents": "Investigation of urine transport in the ureter of the pig by x-ray videodensitometry. II. The effect of an increasing obstruction on velocity, rhythm, and efficiency of the contraction waves. The effect on an increasing acute obstruction on the motility of the ureter was analyzed by means of X-ray videodensitometry. The mean wave velocity decreases and the efficiency of the individual contraction is reduced. The lumen of the ureter is no longer closed completely and an increasing fraction of the urine bolus flows backward. The regurgitation can be seen cineradiographically and assessed semiquantitatively by densitometry."} {"id": "PMID:1270236", "title": "Effect of chlorothiazide and furosemide diuresis on in vivo growth of Staphylococcus aureus in kidneys of mice.", "content": "In mice subcutaneous administration of the diuretics chlorothiazide or furosemide resulted in a prompt diuresis characterized by production of dilute urine within 30 min and lasting for 6 hr. In vivo proliferation or clearance of Staphylococcus aureus from the kidneys was only temporarily impaired during the time of maximum diuresis. When treatment was delayed until after phagocytosis was initiated, there was no effect on clearance. Clinically it would appear that bacterial proliferations in the renal parenchyma would not be promoted as a consequence of diuretic treatment.", "contents": "Effect of chlorothiazide and furosemide diuresis on in vivo growth of Staphylococcus aureus in kidneys of mice. In mice subcutaneous administration of the diuretics chlorothiazide or furosemide resulted in a prompt diuresis characterized by production of dilute urine within 30 min and lasting for 6 hr. In vivo proliferation or clearance of Staphylococcus aureus from the kidneys was only temporarily impaired during the time of maximum diuresis. When treatment was delayed until after phagocytosis was initiated, there was no effect on clearance. Clinically it would appear that bacterial proliferations in the renal parenchyma would not be promoted as a consequence of diuretic treatment."} {"id": "PMID:1270237", "title": "The effect of radiation on prostatic growth.", "content": "Radiation is increasingly important in the treatment of prostatic carcinoma. The effect and mechanism of action of radiation on prostatic growth was studied using the ventral prostate of the testosterone-treated rat. Prostatic radiation blocked testosterone-stimulated prostatic growth. Electron microscopy showed this inhibition to be associated with specific morphologic alterations. While radiation caused profound inhibition of prostatic DNA synthesis, only modest effects on nuclear uptake of dihydrotestosterone and on prostatic 5alpha-reductase were observed. Based on these animal studies, it is concluded that a major mechanism whereby radiation blocks testosterone-stimulated prostatic growth operates through inhibition of DNA synthesis.", "contents": "The effect of radiation on prostatic growth. Radiation is increasingly important in the treatment of prostatic carcinoma. The effect and mechanism of action of radiation on prostatic growth was studied using the ventral prostate of the testosterone-treated rat. Prostatic radiation blocked testosterone-stimulated prostatic growth. Electron microscopy showed this inhibition to be associated with specific morphologic alterations. While radiation caused profound inhibition of prostatic DNA synthesis, only modest effects on nuclear uptake of dihydrotestosterone and on prostatic 5alpha-reductase were observed. Based on these animal studies, it is concluded that a major mechanism whereby radiation blocks testosterone-stimulated prostatic growth operates through inhibition of DNA synthesis."} {"id": "PMID:1270238", "title": "A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. IV. Anatomy of the perianal spaces.", "content": "A study of the perianal spaces was performed in 22 cadaveric specimens using dissection and microscopic examination. Six spaces could be recognized: subcutaneous, central, intersphincteric, ischiorectal, pelvirectal, and submucous. A mention of the central and intersphincteric spaces could not be traced in the literature. The anatomic relations and communications of the perianal spaces are discussed. The central space occupies the area between the longitudinal muscle termination and the base loop of the external anal sphincter. It is the headquarters of all of the perianal spaces as it communicates with all of them. The intersphincteric spaces lie along the longitudinal anal muscle. They constitute the main tracks for extension of pus along the anal canal. The ischiorectal space communicates directly with main tracks for extension of pus along the anal canal. The ischiorectal space communicates directly with the subcutaneous space without the intervention of a septum. The pelvirectal space communicates with the perianal skin through the intersphincteric spaces. The author failed to demonstrate the musculus submucous space; in its place a collagenous internal anal septum could be identified. Furthermore, no trace for the suspensory ligament of Parks was detected; the lower anal lining was found to be pulled by the medial central septum derived from the central tendon.", "contents": "A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation. IV. Anatomy of the perianal spaces. A study of the perianal spaces was performed in 22 cadaveric specimens using dissection and microscopic examination. Six spaces could be recognized: subcutaneous, central, intersphincteric, ischiorectal, pelvirectal, and submucous. A mention of the central and intersphincteric spaces could not be traced in the literature. The anatomic relations and communications of the perianal spaces are discussed. The central space occupies the area between the longitudinal muscle termination and the base loop of the external anal sphincter. It is the headquarters of all of the perianal spaces as it communicates with all of them. The intersphincteric spaces lie along the longitudinal anal muscle. They constitute the main tracks for extension of pus along the anal canal. The ischiorectal space communicates directly with main tracks for extension of pus along the anal canal. The ischiorectal space communicates directly with the subcutaneous space without the intervention of a septum. The pelvirectal space communicates with the perianal skin through the intersphincteric spaces. The author failed to demonstrate the musculus submucous space; in its place a collagenous internal anal septum could be identified. Furthermore, no trace for the suspensory ligament of Parks was detected; the lower anal lining was found to be pulled by the medial central septum derived from the central tendon."} {"id": "PMID:1270239", "title": "Flutamide. Mechanism of action of a new nonsteroidal antiandrogen.", "content": "Flutamide is a new nonsteroidal antiandrogen useful in the treatment of prostatic carcinoma. The mechanism of action of this compound was investigated using the sex accessory tissue of the male rat. Flutamide was found to block the action of both endogenous and exogenous testosterone and, in addition, to be a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen. Electron microscopic observations further confirm the antiandrogenic properties of flutamide.", "contents": "Flutamide. Mechanism of action of a new nonsteroidal antiandrogen. Flutamide is a new nonsteroidal antiandrogen useful in the treatment of prostatic carcinoma. The mechanism of action of this compound was investigated using the sex accessory tissue of the male rat. Flutamide was found to block the action of both endogenous and exogenous testosterone and, in addition, to be a potent inhibitor of testosterone-stimulated prostatic DNA synthesis. Moreover, it is capable of inhibiting prostatic nuclear uptake of androgen. Electron microscopic observations further confirm the antiandrogenic properties of flutamide."} {"id": "PMID:1270240", "title": "Viscoelastic properties of bladder wall strips at constant elongation.", "content": "The experimental and data processing methods used were improved in several respects compared with those described in previous publications. One hundred twenty-two stress decrease curves for bladder wall strips were measured at constant elongation; reproducibility was tested. Consideration of the results led to the addition of two elements (a dashpot and an active element) to our model of the process involved. The influence of the dashpot on the measurements is mathematically analyzed in terms of an increase in rest length during stretch. The model could be successfully fitted to the experimental data and the parameters turned out to be in the physiologic range. Some recent models used to describe muscular stress relaxation were tested and criticized.", "contents": "Viscoelastic properties of bladder wall strips at constant elongation. The experimental and data processing methods used were improved in several respects compared with those described in previous publications. One hundred twenty-two stress decrease curves for bladder wall strips were measured at constant elongation; reproducibility was tested. Consideration of the results led to the addition of two elements (a dashpot and an active element) to our model of the process involved. The influence of the dashpot on the measurements is mathematically analyzed in terms of an increase in rest length during stretch. The model could be successfully fitted to the experimental data and the parameters turned out to be in the physiologic range. Some recent models used to describe muscular stress relaxation were tested and criticized."} {"id": "PMID:1270241", "title": "Compensatory renal adaptation after progressive renal ablation.", "content": "A quantitative study of compensatory adaptation in renal growth, function, and blood flow after progressive renal ablation was performed in the rat. Four weeks after surgery, renal mass increased 31% in control animals (Group A), 81% in nephrectomized rats with 50% ablation of total renal mass (Group B), and 168% in rats subjected to 75% ablation of total renal mass (Group C). Whole animal glomerular filtration rate (GFR) was reduced to 68% of control levels after nephrectomy (Group B), while renal blood flow (RBF) was 81% of control. Similarly, RBF was 68% of control in Group C with ablation of 75% of renal mass, while GFR was reduced to 49% of control. Since the adaptive increases in RBF exceeded those of GRF, the filtration fraction fell from 0.39 in Group A to 0.35 in Group B, and to 0.29 in Group C. Mean nephron GFR (whole animal GFR per total number of glomeruli) was 47 nl per min in Group A and increased 60% to 76 nl per min in Group B and 136% to 112 nl per min in Group C. Compensatory changes in mean nephron blood flow (RBF per total number of glomeruli) exceeded those of nephron filtration rate. Mean nephron blood flow increased from 215 nl per min in Group A to 404 nl per min in Group B (88%) and to 724 nl per min in Group C (237% over contol). These data indicate that the compensatory changes in growth, function, and blood flow after resection of renal mass correlate with the amount of tissue removed. Changes in RBF parallel but exceed those of mass and function, especially after extensive renal ablation. No apparent limitation to the compensatory response was seen under the conditions of this study.", "contents": "Compensatory renal adaptation after progressive renal ablation. A quantitative study of compensatory adaptation in renal growth, function, and blood flow after progressive renal ablation was performed in the rat. Four weeks after surgery, renal mass increased 31% in control animals (Group A), 81% in nephrectomized rats with 50% ablation of total renal mass (Group B), and 168% in rats subjected to 75% ablation of total renal mass (Group C). Whole animal glomerular filtration rate (GFR) was reduced to 68% of control levels after nephrectomy (Group B), while renal blood flow (RBF) was 81% of control. Similarly, RBF was 68% of control in Group C with ablation of 75% of renal mass, while GFR was reduced to 49% of control. Since the adaptive increases in RBF exceeded those of GRF, the filtration fraction fell from 0.39 in Group A to 0.35 in Group B, and to 0.29 in Group C. Mean nephron GFR (whole animal GFR per total number of glomeruli) was 47 nl per min in Group A and increased 60% to 76 nl per min in Group B and 136% to 112 nl per min in Group C. Compensatory changes in mean nephron blood flow (RBF per total number of glomeruli) exceeded those of nephron filtration rate. Mean nephron blood flow increased from 215 nl per min in Group A to 404 nl per min in Group B (88%) and to 724 nl per min in Group C (237% over contol). These data indicate that the compensatory changes in growth, function, and blood flow after resection of renal mass correlate with the amount of tissue removed. Changes in RBF parallel but exceed those of mass and function, especially after extensive renal ablation. No apparent limitation to the compensatory response was seen under the conditions of this study."} {"id": "PMID:1270242", "title": "Intravenous pyelographic visualization after complete ureteral obstruction with hypertonic solute loading.", "content": "Intravenous pyelography was performed after complete unilateral ureteral obstruction in dogs under conditions of mannitol diuresis and 3% NaCl solute loading. Pyelographic visualization with mannitol diuresis was uniformly poor. Satisfactory intravenous pyelograms were obtained in the 3% NaCl solute loaded group during the first 2 weeks, with nephrogram visualization noted up to 45 days postocclusion. The clinical use of pyelography, boosted by hypertonic solute loading during the early period after complete ureteral obstruction, may yield unexpected good quality studies.", "contents": "Intravenous pyelographic visualization after complete ureteral obstruction with hypertonic solute loading. Intravenous pyelography was performed after complete unilateral ureteral obstruction in dogs under conditions of mannitol diuresis and 3% NaCl solute loading. Pyelographic visualization with mannitol diuresis was uniformly poor. Satisfactory intravenous pyelograms were obtained in the 3% NaCl solute loaded group during the first 2 weeks, with nephrogram visualization noted up to 45 days postocclusion. The clinical use of pyelography, boosted by hypertonic solute loading during the early period after complete ureteral obstruction, may yield unexpected good quality studies."} {"id": "PMID:1270255", "title": "[The lymphocyte transformation test in dermatology].", "content": "At first, immunologie and methodic basies of the lymphocyte transformation test are discussed. Then the results gained by this test in several dermatologic diseases are summarized. Finally, practice of the lymphocyte transformation test is critically reviewed.", "contents": "[The lymphocyte transformation test in dermatology]. At first, immunologie and methodic basies of the lymphocyte transformation test are discussed. Then the results gained by this test in several dermatologic diseases are summarized. Finally, practice of the lymphocyte transformation test is critically reviewed."} {"id": "PMID:1270256", "title": "[Round-headed spermatozoa: a rare andrologic finding (\"globe-headed spermatozoa\", \"globozoospermia\")].", "content": "The case of an infertile patient is reported who had 100% round-headed (\"globe-headed\") spermatozoa without acrosomes in his ejaculate. The spermatozoa were studied by light and phase contrast microscopy, as well as by transmission and--for the first time--by scanning electron microscopy. Determination of acrosin showed no enzyme activity. We propose the term \"globozoospermia\" for this condition which was first described in 1971. It is discussed whether it may be considered as a symptom or a distinct disease.", "contents": "[Round-headed spermatozoa: a rare andrologic finding (\"globe-headed spermatozoa\", \"globozoospermia\")]. The case of an infertile patient is reported who had 100% round-headed (\"globe-headed\") spermatozoa without acrosomes in his ejaculate. The spermatozoa were studied by light and phase contrast microscopy, as well as by transmission and--for the first time--by scanning electron microscopy. Determination of acrosin showed no enzyme activity. We propose the term \"globozoospermia\" for this condition which was first described in 1971. It is discussed whether it may be considered as a symptom or a distinct disease."} {"id": "PMID:1270257", "title": "[Elastoma perforans serpigiosum].", "content": "After a survey of the literature a case of \"elastoma perforans serpiginosum\" - characteristic from the clinical and histological viewpoint - is discussed. Our findings reveal that it deals with an \"elastica-degeneration\" within a zone of inflammation. Its catabolic products are discharged as necrotic masses through the epithelium or the follicles to the outside. Despite of the imposing clinical appearance it is not primarily a keratosis. The massive proliferation is secondary. The \"forceps-like\" enclosure of necrotic masses by proliferating epithelium may stimulate a space within the follicle. Aetiopathogenesis and therapy are discussed.", "contents": "[Elastoma perforans serpigiosum]. After a survey of the literature a case of \"elastoma perforans serpiginosum\" - characteristic from the clinical and histological viewpoint - is discussed. Our findings reveal that it deals with an \"elastica-degeneration\" within a zone of inflammation. Its catabolic products are discharged as necrotic masses through the epithelium or the follicles to the outside. Despite of the imposing clinical appearance it is not primarily a keratosis. The massive proliferation is secondary. The \"forceps-like\" enclosure of necrotic masses by proliferating epithelium may stimulate a space within the follicle. Aetiopathogenesis and therapy are discussed."} {"id": "PMID:1270258", "title": "[The radiophosphorus (32P)-test in precanceroses and malignant tumors of the skin].", "content": "In 21 patients with a variety of skin tumors (squamous cell carcinomas, malignant melanomas, basal cell epitheliomas and mycosis fungoides) or pre-cancerous lesions (Bowen's disease, actinic keratosis, junctional nevus cell nevus) the radioactive phosphorus uptake test demonstrates a significantly increased concentration of P32 in those tumors. There were no false negative tests. The possibility of differentiation of malignant melanoma from benign nevus cell nevus and the early recognition of cutaneous metastases is described. Furthermore recurrence of previously irradiated or excised basal cell epitheliomas can be detected without a biopsy. No hematological side-effects were observed.", "contents": "[The radiophosphorus (32P)-test in precanceroses and malignant tumors of the skin]. In 21 patients with a variety of skin tumors (squamous cell carcinomas, malignant melanomas, basal cell epitheliomas and mycosis fungoides) or pre-cancerous lesions (Bowen's disease, actinic keratosis, junctional nevus cell nevus) the radioactive phosphorus uptake test demonstrates a significantly increased concentration of P32 in those tumors. There were no false negative tests. The possibility of differentiation of malignant melanoma from benign nevus cell nevus and the early recognition of cutaneous metastases is described. Furthermore recurrence of previously irradiated or excised basal cell epitheliomas can be detected without a biopsy. No hematological side-effects were observed."} {"id": "PMID:1270260", "title": "The number of personnel needed to perform examinations.", "content": "The Association of State and Territorial Public Health Laboratory Directors and the Center for Disease Control jointly developed a relative value system for measuring laboratory workload and productivity. This system has also served as a basis for determining the cost of tests. An additional usage, estimating both the number and grade levels of personnel needed by a laboratory to perform examinations, is explained in this article.", "contents": "The number of personnel needed to perform examinations. The Association of State and Territorial Public Health Laboratory Directors and the Center for Disease Control jointly developed a relative value system for measuring laboratory workload and productivity. This system has also served as a basis for determining the cost of tests. An additional usage, estimating both the number and grade levels of personnel needed by a laboratory to perform examinations, is explained in this article."} {"id": "PMID:1270261", "title": "Effects of pooled samples.", "content": "Pooling of specimens before testing may reduce the costs of expensive tests for rare conditions. This paper presents models of how test performance is degraded by such pools, and of the financial savings that pooling allows. The method of computing optimal pool size is demonstrated on a screening test and on the test for gastrin. Test characteristics that make pooling especially effective are listed.", "contents": "Effects of pooled samples. Pooling of specimens before testing may reduce the costs of expensive tests for rare conditions. This paper presents models of how test performance is degraded by such pools, and of the financial savings that pooling allows. The method of computing optimal pool size is demonstrated on a screening test and on the test for gastrin. Test characteristics that make pooling especially effective are listed."} {"id": "PMID:1270262", "title": "Mycoplasma in biological systems: induction of interferon.", "content": "Mycoplasmal infection leads to a variety of effects on host cells both in vivo and in vitro. Among these is the induction of interferon, which has been demonstrated in mycoplasma-infected human and sheep lymphoreticular cell cultures and in mice. Different species and strains of mycoplasma vary in their ability to induce interferon in these experimental models. Several studies have shown that mycoplasmas do not elicit the production of interferon in murine cells in vitro or in non-lymphoreticular cells of other animal species. This may be related to the ability of host cells to take up mycoplasmas or to mycoplasma-associated products, such as mycoplasmal viruses. Initial studies of mixed infections with mycoplasmas and animal viruses in vivo have demonstrated both an inhibition and an enhancement of viral disease, indicating the complex nature of mycoplasma-animal virus interactions.", "contents": "Mycoplasma in biological systems: induction of interferon. Mycoplasmal infection leads to a variety of effects on host cells both in vivo and in vitro. Among these is the induction of interferon, which has been demonstrated in mycoplasma-infected human and sheep lymphoreticular cell cultures and in mice. Different species and strains of mycoplasma vary in their ability to induce interferon in these experimental models. Several studies have shown that mycoplasmas do not elicit the production of interferon in murine cells in vitro or in non-lymphoreticular cells of other animal species. This may be related to the ability of host cells to take up mycoplasmas or to mycoplasma-associated products, such as mycoplasmal viruses. Initial studies of mixed infections with mycoplasmas and animal viruses in vivo have demonstrated both an inhibition and an enhancement of viral disease, indicating the complex nature of mycoplasma-animal virus interactions."} {"id": "PMID:1270263", "title": "Mycoplasmas in humans: significance of Ureaplasma urealyticum.", "content": "Isolation of mycoplasmas from clinical specimens has resulted in compelling evidence that in addition to M. pneumoniae, the documented pathogen, the T strain mycoplasmas are not always benign commensals colonizing the mucous membranes of the genitourinary tract of men and women, but may be actively involved in infection with sequelae expressed as nongonococcal urethritis and some form of reproductive wastage such as infertility, spontaneous abortion and premature births.", "contents": "Mycoplasmas in humans: significance of Ureaplasma urealyticum. Isolation of mycoplasmas from clinical specimens has resulted in compelling evidence that in addition to M. pneumoniae, the documented pathogen, the T strain mycoplasmas are not always benign commensals colonizing the mucous membranes of the genitourinary tract of men and women, but may be actively involved in infection with sequelae expressed as nongonococcal urethritis and some form of reproductive wastage such as infertility, spontaneous abortion and premature births."} {"id": "PMID:1270264", "title": "Infertility of cattle caused by mycoplasmas.", "content": "Mycoplasmas have been well established as pathogens of the bovine urogenital tract, and produce pathologic lesions resulting in infertility. Serologic examination of cattle with infertility problems with Mycoplasma bovigenitalium and Mycoplasma agalactiae subsp. bovis show a high incidence of positive reactors suggesting that mycoplasmas play an important role in bovine infertility. The similarities of pathologic lesions in the urogenital tract of cattle and women with infertility problems and the frequency of isolation of mycoplasmas from human females suggest closer examination for mycoplasmas in human infertility. Studies with bulls suggest that mycoplasmas as a cause of human male infertility should not be ignored.", "contents": "Infertility of cattle caused by mycoplasmas. Mycoplasmas have been well established as pathogens of the bovine urogenital tract, and produce pathologic lesions resulting in infertility. Serologic examination of cattle with infertility problems with Mycoplasma bovigenitalium and Mycoplasma agalactiae subsp. bovis show a high incidence of positive reactors suggesting that mycoplasmas play an important role in bovine infertility. The similarities of pathologic lesions in the urogenital tract of cattle and women with infertility problems and the frequency of isolation of mycoplasmas from human females suggest closer examination for mycoplasmas in human infertility. Studies with bulls suggest that mycoplasmas as a cause of human male infertility should not be ignored."} {"id": "PMID:1270294", "title": "[Regulation factors of stomach emptying in dogs].", "content": "Gastric emptying of organic acids was studied in 6 healthy mongrel dogs. After chronic esophagostomies were performed according to the method of Komarov, a total of 340 test meals were instilled. Each test meal consisted of 300 ml of 6 different organic acids with decreasing molecular weight and different concentrations. After the experiments were achieved, each dog underwent a proximal gastric vagotomy according to the method of Amdrup, and experiments with citric acid were repeated. The results may be summarized as follows: multiple stepwise regression analysis of the data is consistent with a model in which gastric emptying of organic acids is regulated by 3 receptors. The receptors respond to concentration of the organic acid, the actual volume, and the type of acid. The volume receptor is located in the corpus of the stomach because the effect of volume accelerates the emptying rate after proximal gastric vagotomy while the effects of concentration and type of acid remain unchanged.", "contents": "[Regulation factors of stomach emptying in dogs]. Gastric emptying of organic acids was studied in 6 healthy mongrel dogs. After chronic esophagostomies were performed according to the method of Komarov, a total of 340 test meals were instilled. Each test meal consisted of 300 ml of 6 different organic acids with decreasing molecular weight and different concentrations. After the experiments were achieved, each dog underwent a proximal gastric vagotomy according to the method of Amdrup, and experiments with citric acid were repeated. The results may be summarized as follows: multiple stepwise regression analysis of the data is consistent with a model in which gastric emptying of organic acids is regulated by 3 receptors. The receptors respond to concentration of the organic acid, the actual volume, and the type of acid. The volume receptor is located in the corpus of the stomach because the effect of volume accelerates the emptying rate after proximal gastric vagotomy while the effects of concentration and type of acid remain unchanged."} {"id": "PMID:1270297", "title": "[A fixation apparatus for differential indication on fibular band lesions].", "content": "Description of a new radiological technique for examination of lesions of the lateral ligaments of the ankle. With this method it is possible to make differential diagnosis. The drawer sign of the talus is measured. In contrast with conventional stress a.-p. roentgenograms it is also possible to detect isolated tears of the anterior talo-fibular ligament. Additional advantages of the method are no X-ray exposure for the examiner, local anaesthesia is not required and the results are reproducible independent of the examiner.", "contents": "[A fixation apparatus for differential indication on fibular band lesions]. Description of a new radiological technique for examination of lesions of the lateral ligaments of the ankle. With this method it is possible to make differential diagnosis. The drawer sign of the talus is measured. In contrast with conventional stress a.-p. roentgenograms it is also possible to detect isolated tears of the anterior talo-fibular ligament. Additional advantages of the method are no X-ray exposure for the examiner, local anaesthesia is not required and the results are reproducible independent of the examiner."} {"id": "PMID:1270298", "title": "[Therapeutic hazard of supracondylar humeral fracture in a child].", "content": "A case of a supracondylar fracture in a 4-year-old female is presented. The risks of treatment are discussed. The question is raised whether the complication which resulted could have been avoided.", "contents": "[Therapeutic hazard of supracondylar humeral fracture in a child]. A case of a supracondylar fracture in a 4-year-old female is presented. The risks of treatment are discussed. The question is raised whether the complication which resulted could have been avoided."} {"id": "PMID:1270300", "title": "[Experiences with AO-semitubular plate in the stabilization of ankle fractures].", "content": "Anatomical restoration of the lateral malleolus in ankle dislocation fractures is known to be very important. With the AO-small semitubular plate an armamentarium is available which accomplishes this task very well. Exercising stability nearly always can be attained. In case of postoperative infection, healing generally takes place without plate removing and, therefore, under good fracture position.", "contents": "[Experiences with AO-semitubular plate in the stabilization of ankle fractures]. Anatomical restoration of the lateral malleolus in ankle dislocation fractures is known to be very important. With the AO-small semitubular plate an armamentarium is available which accomplishes this task very well. Exercising stability nearly always can be attained. In case of postoperative infection, healing generally takes place without plate removing and, therefore, under good fracture position."} {"id": "PMID:1270301", "title": "[Valve of plastic repair of the deep femoral artery in chronic circulatory disease of the lower extremities].", "content": "It is reported about indication, surgical technique, early and late postoperative results of the plastic of the profunda femoris artery. On 17, mainly old patients with chronic circulatory disease of the lower limbs was this operation carried out, because a longer angioplastic operative procedure would have been a great risk. The statement, that 47% of our patients were practically without symptoms after four years is promising for the plastic of the profunda femoris artery with chronic ischemia syndrome of the lower limbs.", "contents": "[Valve of plastic repair of the deep femoral artery in chronic circulatory disease of the lower extremities]. It is reported about indication, surgical technique, early and late postoperative results of the plastic of the profunda femoris artery. On 17, mainly old patients with chronic circulatory disease of the lower limbs was this operation carried out, because a longer angioplastic operative procedure would have been a great risk. The statement, that 47% of our patients were practically without symptoms after four years is promising for the plastic of the profunda femoris artery with chronic ischemia syndrome of the lower limbs."} {"id": "PMID:1270302", "title": "[Appendiceal carcinoma].", "content": "Three cases of carcinoma of the vermiform appendix are reported. The rarity of the disease has been emphasized as well as the resulting lack of clinical experience. Medical literature on the subject has been reviewed.", "contents": "[Appendiceal carcinoma]. Three cases of carcinoma of the vermiform appendix are reported. The rarity of the disease has been emphasized as well as the resulting lack of clinical experience. Medical literature on the subject has been reviewed."} {"id": "PMID:1270303", "title": "[Complications in bronchoplastic surgery of benign and malignant lung neoplasms].", "content": "Out of 1629 patients who were hospitalised 1963 to 1973 for diagnosis and treatment of bronchogenic tumors, 731 underwent resection. 20 patients could be operated upon by lobectomy or bilobectomy and bronchial resection (Sleeve-resection). In two other patients the tumor could be resected through a bronchotomy. Postoperative complications were frequent (n = 6) on patients with malignant tumors (n= 15). We saw 3 times a bronchopleural fistula (2 patients had to be reoperated, 1 death), once a fatal empyema, once a fatal pneumonia of the contralateral side and once a bronchial stenosis of 50% of the lumen. On the patients with a benign tumor (n = 7) we saw in one patient a bronchopleural fistula and in another endobronchialgranulomas due to non resorbable suture material. Methods to prevent or cure these complications are presented consisting in the use of absorbable suture material and long lasting intrathoracic suction.", "contents": "[Complications in bronchoplastic surgery of benign and malignant lung neoplasms]. Out of 1629 patients who were hospitalised 1963 to 1973 for diagnosis and treatment of bronchogenic tumors, 731 underwent resection. 20 patients could be operated upon by lobectomy or bilobectomy and bronchial resection (Sleeve-resection). In two other patients the tumor could be resected through a bronchotomy. Postoperative complications were frequent (n = 6) on patients with malignant tumors (n= 15). We saw 3 times a bronchopleural fistula (2 patients had to be reoperated, 1 death), once a fatal empyema, once a fatal pneumonia of the contralateral side and once a bronchial stenosis of 50% of the lumen. On the patients with a benign tumor (n = 7) we saw in one patient a bronchopleural fistula and in another endobronchialgranulomas due to non resorbable suture material. Methods to prevent or cure these complications are presented consisting in the use of absorbable suture material and long lasting intrathoracic suction."} {"id": "PMID:1270316", "title": "[Indicatory and technical faults as cause of postoperative complications in arterial surgery].", "content": "In all vascular surgery the technic and quality of the first operation is a factor of decisive importance for the long-term results. The need to perform a second or third operation considerably reduces the chances of success. Routine use of an intra-operative control method like arteriography or vascular endoscopy, makes a decisive contribution in the peripheral circulation of the limbs to the immediate detection of errors of operative technic and their correction during the same operation. A change of indication for occlusive processes in the femoropopliteal branch is evident: patients with claudication should be treated with profunda revascularisation combined with lumbal sympathectomy and patients with rest-pain and necrosis should be treated with venous autografts using a microsurgical technic. To avoid deep wound infections the selection of an incision line which does not damage the lymphatic channels, particularly in the groin, the short duration of operations and the use of a purely instrumental operative technic with minimal damage to the tissues are of decisive importance. Examples are used to illustrate errors of indication and technic and the post-operative sequelae of such errors.", "contents": "[Indicatory and technical faults as cause of postoperative complications in arterial surgery]. In all vascular surgery the technic and quality of the first operation is a factor of decisive importance for the long-term results. The need to perform a second or third operation considerably reduces the chances of success. Routine use of an intra-operative control method like arteriography or vascular endoscopy, makes a decisive contribution in the peripheral circulation of the limbs to the immediate detection of errors of operative technic and their correction during the same operation. A change of indication for occlusive processes in the femoropopliteal branch is evident: patients with claudication should be treated with profunda revascularisation combined with lumbal sympathectomy and patients with rest-pain and necrosis should be treated with venous autografts using a microsurgical technic. To avoid deep wound infections the selection of an incision line which does not damage the lymphatic channels, particularly in the groin, the short duration of operations and the use of a purely instrumental operative technic with minimal damage to the tissues are of decisive importance. Examples are used to illustrate errors of indication and technic and the post-operative sequelae of such errors."} {"id": "PMID:1270319", "title": "Fundus photography in neonates, an approach to obtain indirect information on cerebral blood flow.", "content": "In view of the possibility to obtain indirect information on the interdependency between brain tissue metabolish and the diameter of the intraparenchymatous arterioles through measurement of systemic blood gases and blood pressure on one hand and the diameter of the central retinal artery on the other, we describe a modified method of fundus photography which is practical for neonatologists owing to the simplification brought about by the use of a special contact lens. In an appendix the relevant optical data are analyzed. Fundus photographs of neonates suffering from cardiac malformation or asphyxia are shown.", "contents": "Fundus photography in neonates, an approach to obtain indirect information on cerebral blood flow. In view of the possibility to obtain indirect information on the interdependency between brain tissue metabolish and the diameter of the intraparenchymatous arterioles through measurement of systemic blood gases and blood pressure on one hand and the diameter of the central retinal artery on the other, we describe a modified method of fundus photography which is practical for neonatologists owing to the simplification brought about by the use of a special contact lens. In an appendix the relevant optical data are analyzed. Fundus photographs of neonates suffering from cardiac malformation or asphyxia are shown."} {"id": "PMID:1270320", "title": "[Plasma aldosterone in childhood].", "content": "According to a radioimmunological method modified in our laboratory we determined plasma aldosterone levels under standardized conditions in children of different age from 2 weeks to 14 years, in women undergoing uncomplicated vaginal delivery, and in the cord blood of the corresponding newborn babies. Furthermore, the effect of different stimulating factors (ACTH, salt restriction, severe vomiting, fever) in children was studied. In mothers and cord blood we found 68.6 +/- 39.3 ng/100 ml and 75.5 +/- 37.4 ng/100 ml, respectively. In the first two years of life there is a decrease in plasma aldosterone levels to the relatively constant concentration at the age of 2 to 14 years (7.3 +/- 4.7 ng/100 ml). The age groups 2 weeks to 1 year, 1 to 2 years and 2 to 14 years all show significant differences. A correlation of age (first two years of life) and plasma aldosterone level could be shown (correlation coefficient -0.50 according to Pearson). The stimulation results are comparable with literature data concerning adults. The mechanism of stimulation by vomiting and fever is discussed.", "contents": "[Plasma aldosterone in childhood]. According to a radioimmunological method modified in our laboratory we determined plasma aldosterone levels under standardized conditions in children of different age from 2 weeks to 14 years, in women undergoing uncomplicated vaginal delivery, and in the cord blood of the corresponding newborn babies. Furthermore, the effect of different stimulating factors (ACTH, salt restriction, severe vomiting, fever) in children was studied. In mothers and cord blood we found 68.6 +/- 39.3 ng/100 ml and 75.5 +/- 37.4 ng/100 ml, respectively. In the first two years of life there is a decrease in plasma aldosterone levels to the relatively constant concentration at the age of 2 to 14 years (7.3 +/- 4.7 ng/100 ml). The age groups 2 weeks to 1 year, 1 to 2 years and 2 to 14 years all show significant differences. A correlation of age (first two years of life) and plasma aldosterone level could be shown (correlation coefficient -0.50 according to Pearson). The stimulation results are comparable with literature data concerning adults. The mechanism of stimulation by vomiting and fever is discussed."} {"id": "PMID:1270321", "title": "Urinary hydroxyproline values following continuous and intermittent administration of prednisolone in children.", "content": "The administration of 2 mg/kg body weight of prednisolone daily in divided doses to 5 healthy children aged 5-7 years resulted in a significant decrease in the amount of total urinary hydroxyproline (HOP) which was restored to pretreatment levels two weeks after discontinuation of the drug. On the other hand, the administration of 2 mg/kg body weight of prednisolone in a single dose on alternate days (every-other-day) to two children and for a period of 10 days caused insignificant alterations in the amount of urinary HOP.", "contents": "Urinary hydroxyproline values following continuous and intermittent administration of prednisolone in children. The administration of 2 mg/kg body weight of prednisolone daily in divided doses to 5 healthy children aged 5-7 years resulted in a significant decrease in the amount of total urinary hydroxyproline (HOP) which was restored to pretreatment levels two weeks after discontinuation of the drug. On the other hand, the administration of 2 mg/kg body weight of prednisolone in a single dose on alternate days (every-other-day) to two children and for a period of 10 days caused insignificant alterations in the amount of urinary HOP."} {"id": "PMID:1270322", "title": "Reye's syndrome without fatty liver.", "content": "A 2 1/2-year-old child died after an illness of three days duration, characterized by a sudden onset, vomiting, coma and a striking hyperammonemia. At autopsy, the liver was practically normal. This is a further example of Reye's syndrome with only minimal fatty infiltration of the liver. It appears that the classical massive and diffuse fatty degeneration of the liver is not an essential feature of the syndrome. The evidence for this is discussed.", "contents": "Reye's syndrome without fatty liver. A 2 1/2-year-old child died after an illness of three days duration, characterized by a sudden onset, vomiting, coma and a striking hyperammonemia. At autopsy, the liver was practically normal. This is a further example of Reye's syndrome with only minimal fatty infiltration of the liver. It appears that the classical massive and diffuse fatty degeneration of the liver is not an essential feature of the syndrome. The evidence for this is discussed."} {"id": "PMID:1270323", "title": "Pancreatic ascites in the first year of life.", "content": "A case of pancreatic ascites in a 4-month-old baby girl is reported. To the best of our knowledge only 4 previous cases occurring in the first year of life have been reported in the pediatric literature. In patients with unexplained ascites, amylase determination should be performed on ascitic fluid and serum. The baby was first treated by external drainage and later by internal drainage of the pseudocyst which had formed along the fistula.", "contents": "Pancreatic ascites in the first year of life. A case of pancreatic ascites in a 4-month-old baby girl is reported. To the best of our knowledge only 4 previous cases occurring in the first year of life have been reported in the pediatric literature. In patients with unexplained ascites, amylase determination should be performed on ascitic fluid and serum. The baby was first treated by external drainage and later by internal drainage of the pseudocyst which had formed along the fistula."} {"id": "PMID:1270324", "title": "Congenital neuroblastoma with paraplegia. Case report.", "content": "A case of congenital neuroblastoma presenting with paraplegia in a newborn baby is described. The tumor was removed and chemotherapy was given. The child is now 2 years old, without relapse, but still suffers from flaccid paralysis and anaesthesia of both legs.", "contents": "Congenital neuroblastoma with paraplegia. Case report. A case of congenital neuroblastoma presenting with paraplegia in a newborn baby is described. The tumor was removed and chemotherapy was given. The child is now 2 years old, without relapse, but still suffers from flaccid paralysis and anaesthesia of both legs."} {"id": "PMID:1270325", "title": "Haematological studies in a new variant of glucosephosphate isomerase deficiency (GPI Utrecht).", "content": "The haematological data in a 9-year-old Dutch child suffering from an unusual new variant of glucose-6-phosphate isomerase deficiency (GPI Utrecht) are discussed. Symptoms and signs differ in many respects from those generally observed in GPI deficiency, as mental retardation, drug sensitivity and increased susceptibility to infections were present. Extensive studies on mechanisms involved in drug-sensitive haemolytic anaemia did not reveal its causes. Though the defect was generalized, no disturbance in granulocyte and thrombocyte functions were detected.", "contents": "Haematological studies in a new variant of glucosephosphate isomerase deficiency (GPI Utrecht). The haematological data in a 9-year-old Dutch child suffering from an unusual new variant of glucose-6-phosphate isomerase deficiency (GPI Utrecht) are discussed. Symptoms and signs differ in many respects from those generally observed in GPI deficiency, as mental retardation, drug sensitivity and increased susceptibility to infections were present. Extensive studies on mechanisms involved in drug-sensitive haemolytic anaemia did not reveal its causes. Though the defect was generalized, no disturbance in granulocyte and thrombocyte functions were detected."} {"id": "PMID:1270326", "title": "An inherited defect in granulocyte function: impaired chemotaxis, phagocytosis and intracellular killing of microorganisms.", "content": "The neutrophil granulocytes of a 1-year-old boy with severe recurrent infections were found to have almost no chemotactic responsiveness, impaired phagocytosis and reduced intracellular killing of Candida albicans \"in vitro\". During the course of a febrile illness of unknown etiology which was accompanied by a leukemoid reaction, phagocytic activity became normal; the chemotactic response was also increased but still remained slightly subnormal. Family studies suggested that the defect was an inherited autosomal recessive one.", "contents": "An inherited defect in granulocyte function: impaired chemotaxis, phagocytosis and intracellular killing of microorganisms. The neutrophil granulocytes of a 1-year-old boy with severe recurrent infections were found to have almost no chemotactic responsiveness, impaired phagocytosis and reduced intracellular killing of Candida albicans \"in vitro\". During the course of a febrile illness of unknown etiology which was accompanied by a leukemoid reaction, phagocytic activity became normal; the chemotactic response was also increased but still remained slightly subnormal. Family studies suggested that the defect was an inherited autosomal recessive one."} {"id": "PMID:1270327", "title": "Epidermolysis bullosa hereditaria letalis: report of a case and probable ultrastructural defects.", "content": "A case of epidermolysis bullosa hereditaria letalis (Herlitz) is described. In accordance with findings in other cases of Herlitz disease blister formation occurs in form of junctional separation. Electron microscopic study revealed scarcity and abnormal structure of hemidesmosomes, which may play an important role in the pathomorphogenesis of junctional blistering.", "contents": "Epidermolysis bullosa hereditaria letalis: report of a case and probable ultrastructural defects. A case of epidermolysis bullosa hereditaria letalis (Herlitz) is described. In accordance with findings in other cases of Herlitz disease blister formation occurs in form of junctional separation. Electron microscopic study revealed scarcity and abnormal structure of hemidesmosomes, which may play an important role in the pathomorphogenesis of junctional blistering."} {"id": "PMID:1270329", "title": "The role of the blood-brain barrier in perfusion fixation of the brain for electron microscopy.", "content": "Regions of the brain vascularized by capillaries of the blood-brain barrier (BBB) type require a different fixative from regions which have capillaries of the endocrine type. Fixative with isotonic buffer gives excellent ultrastructural preservation in the BBB regions, but cause severe shrinkage of cells in the endocrine regions. This is evidently due to the difference in the permeability of the capillary walls to solutes in the fixative. In the BBB regions in less permeable capillaries do not allow outflow of osmotically active particles to a harmful extent, whereas in the endocrine regions osomotic imbalances are created between the intra- and extracellular compartments. The diffusion rate of the fixative and the final volume of the fixed brain depend on the balance between the intravascular and intersitial hydrostatic and oncotic pressures across the capillary wall during the perfusion fixation, as those pressures regulate the amount of perfusate that will enter the parenchyma. Generally, as high a perfusion pressure as possible is recommended to obtain effective wash-out of blood and rapid diffusion of fixative into the tissue. Addition of macromolecules (2% PVP, mol. wt. 40,000) into the fixative slightly improved the ultrastructural preservation in the BBB regions of the central nervous system.", "contents": "The role of the blood-brain barrier in perfusion fixation of the brain for electron microscopy. Regions of the brain vascularized by capillaries of the blood-brain barrier (BBB) type require a different fixative from regions which have capillaries of the endocrine type. Fixative with isotonic buffer gives excellent ultrastructural preservation in the BBB regions, but cause severe shrinkage of cells in the endocrine regions. This is evidently due to the difference in the permeability of the capillary walls to solutes in the fixative. In the BBB regions in less permeable capillaries do not allow outflow of osmotically active particles to a harmful extent, whereas in the endocrine regions osomotic imbalances are created between the intra- and extracellular compartments. The diffusion rate of the fixative and the final volume of the fixed brain depend on the balance between the intravascular and intersitial hydrostatic and oncotic pressures across the capillary wall during the perfusion fixation, as those pressures regulate the amount of perfusate that will enter the parenchyma. Generally, as high a perfusion pressure as possible is recommended to obtain effective wash-out of blood and rapid diffusion of fixative into the tissue. Addition of macromolecules (2% PVP, mol. wt. 40,000) into the fixative slightly improved the ultrastructural preservation in the BBB regions of the central nervous system."} {"id": "PMID:1270330", "title": "Some quantitative aspects of Acridine Orange fluorescence in unfixed, sucrose-isolated mammalian nuclei.", "content": "Nuclei were isolated from mouse liver and central nervous system (CNS). These nuclei were fluorochromed without fixation in a 0.25 M sucrose medium containing 5-5 X 10(-5) M Acridin Orange and measured with an incident microfluorometric system. In the case of mouse CNS nuclei, the major and minor axes of the nuclei were measured with a filar micrometer. Three modal values were obtained from the hepatocyte suspension corresponding to 2C, 4C, and 8C nuclei, respectively. While the CNS nuclei displayed substantial variability in size, the Acridine Orange emission values at 530 nm were nearly constant. The data suggest that under these conditions, Acridine Orange fuorescence reflects DNA content. Further, the 530 nm fluorescence emission is not affected by chromatin condensation or proteins complexed with DNA.", "contents": "Some quantitative aspects of Acridine Orange fluorescence in unfixed, sucrose-isolated mammalian nuclei. Nuclei were isolated from mouse liver and central nervous system (CNS). These nuclei were fluorochromed without fixation in a 0.25 M sucrose medium containing 5-5 X 10(-5) M Acridin Orange and measured with an incident microfluorometric system. In the case of mouse CNS nuclei, the major and minor axes of the nuclei were measured with a filar micrometer. Three modal values were obtained from the hepatocyte suspension corresponding to 2C, 4C, and 8C nuclei, respectively. While the CNS nuclei displayed substantial variability in size, the Acridine Orange emission values at 530 nm were nearly constant. The data suggest that under these conditions, Acridine Orange fuorescence reflects DNA content. Further, the 530 nm fluorescence emission is not affected by chromatin condensation or proteins complexed with DNA."} {"id": "PMID:1270331", "title": "Zonal rotor analysis of the subcellular localization of alpha-glycerphosphate dehydrogenase, alpha-naphthyl palmitate and beta-naphthyl laurate hydrolases in the mucosa of the guinea-pig small intestine.", "content": "Whole homogenate of guinea-pig small intestine mucosa was analysed by centrifugation in a zonal rotor. The results indicate that FAD-linked alpha-glycerophosphate dehydrogenase is localized in the mitochondria and that NAD-linked alpha-glycerophosphate dehydrogeanse is a soluble phase enzyme. An enzyme hydrolysing alpha-naphthyl palmitate at an acid pH was localized in the lysosomes and was activated by 0.1% Triton X-100 and by freezing and thawing. An alkaline hydrolase acting on beta-naphthyl laurate was localized in the 'microsomes'. The possibility of this enzyme being different from alpha-naphthyl acetate hydrolase is discussed.", "contents": "Zonal rotor analysis of the subcellular localization of alpha-glycerphosphate dehydrogenase, alpha-naphthyl palmitate and beta-naphthyl laurate hydrolases in the mucosa of the guinea-pig small intestine. Whole homogenate of guinea-pig small intestine mucosa was analysed by centrifugation in a zonal rotor. The results indicate that FAD-linked alpha-glycerophosphate dehydrogenase is localized in the mitochondria and that NAD-linked alpha-glycerophosphate dehydrogeanse is a soluble phase enzyme. An enzyme hydrolysing alpha-naphthyl palmitate at an acid pH was localized in the lysosomes and was activated by 0.1% Triton X-100 and by freezing and thawing. An alkaline hydrolase acting on beta-naphthyl laurate was localized in the 'microsomes'. The possibility of this enzyme being different from alpha-naphthyl acetate hydrolase is discussed."} {"id": "PMID:1270335", "title": "Bulla curettage for chronic otitis media and interna in dogs.", "content": "In a series of 10 clinically affected and 6 clinically normal dogs, the technique of bulla curettage via the external ear canal, after lateral ear resection, was evaluated. In 5 of the 10 dogs with chronic otitis media and interna, the head carriage became normal 2 to 8 weeks after surgery and remained so for at least 18 months; 4 other dogs improved, but the improvement was either temporary or incomplete. In the clinically normal dogs, postsurgical complications were minimal; the tympanic membrane healed completely in 4 of the 6 dogs.", "contents": "Bulla curettage for chronic otitis media and interna in dogs. In a series of 10 clinically affected and 6 clinically normal dogs, the technique of bulla curettage via the external ear canal, after lateral ear resection, was evaluated. In 5 of the 10 dogs with chronic otitis media and interna, the head carriage became normal 2 to 8 weeks after surgery and remained so for at least 18 months; 4 other dogs improved, but the improvement was either temporary or incomplete. In the clinically normal dogs, postsurgical complications were minimal; the tympanic membrane healed completely in 4 of the 6 dogs."} {"id": "PMID:1270340", "title": "Ascites associated with intrahepatic arteriovenous fistula in a cat.", "content": "A 1 1/2-year-old male domestic short-haired cat with ascites was found to have an intrahepatic fistula between the hepatic artery and portal vein. The diagnosis was made by means of angiography. The ascites was attributed to portal hypertension caused by the fistula.", "contents": "Ascites associated with intrahepatic arteriovenous fistula in a cat. A 1 1/2-year-old male domestic short-haired cat with ascites was found to have an intrahepatic fistula between the hepatic artery and portal vein. The diagnosis was made by means of angiography. The ascites was attributed to portal hypertension caused by the fistula."} {"id": "PMID:1270342", "title": "Evaluation of blood urea nitrogen and serum creatinine concentrations as indicators of renal dysfunction: a study of 111 cases and a review of related literature.", "content": "Blood urea nitrogen concentration (BUN), serum creatinine concentration (SC), and BUN/SC ratios, as recorded for 111 dogs and cats with azotemia, were evaluated to determine their usefulness in evaluation of renal dysfunction. Cases were categorized into prerenal, renal, and post-renal causes of azotemia, on the basis of histologic and clinical criteria. The severity of azotemia varied within groups, but the mean value for degree of azotemia was lowest in the prerenal group. The BUN/SC ratios were highest when azotemia was mild, regardless of cause. The BUN/SC ratios in the 3 groups were not significantly different when the degree of azotemia was considered, indicating that differentiation of renal from extrarenal azotemia was not possible in the dog and cat, on the basis of relative values of BUN and SC. Comparison of BUN/SC ratios in acute and chronic azotemia of comparable magnitude revealed no significant differences between groups, indicating that this ratio cannot be used to differentiate acute and chronic azotemia. Following supportive therapy, BUN decreased significantly (P less than 0.05) more than SC, suggesting that extrarenal factors contributed to the increased BUN and that proportionately more urea than creatinine was excreted by the kidneys during therapy. The BUN/SC ratios varied widely and to a similar degree in all groups examined. Inasmuch as the BUN and SC were not correlated with more accurate measurements of renal function, conclusions could not be drawn concerning the superiority of either factor as a measure of renal function. Many nonrenal factors, previously identified, influence serum concentration of urea and creatinine. In recent studies involving azotemic human beings and rats, it was suggested that up to 25% of the urea and 65% of the creatinine produced in the body is degraded by enteric bacteria rather than excreted directly by the kidneys. These data indicate that neither BUN or SC can be used as precise tests of renal function, although SC is subject to alteration by fewer nonrenal factors than is BUN. In older medical and veterinary medical literature, the use of SC as a prognostic indicator had been advocated. Newer findings on the pathophysiology of creatininemia and retrospective case studies do not support this view. In the present study, severe creatininemia was documented in cases in which primary renal dysfunction did not exist. It was concluded that BUN and SC should continue to be regarded as crude indexes of renal function. Clinical value lies in the relative ease of their determination. Because of their lack of sensitivity, more specific evaluation of renal function (urine concentrating ability, phenolsulfonphthalein excretion) may be indicated when BUN and SC are normal or only slightly elevated. Because extrarenal factors may alter BUN and SC, it is necessary to correlate these values with clinical and other laboratory data to differentiate renal from extra-renal azotemia. Single determinations of BUN or SC provide no basis for prognosis.", "contents": "Evaluation of blood urea nitrogen and serum creatinine concentrations as indicators of renal dysfunction: a study of 111 cases and a review of related literature. Blood urea nitrogen concentration (BUN), serum creatinine concentration (SC), and BUN/SC ratios, as recorded for 111 dogs and cats with azotemia, were evaluated to determine their usefulness in evaluation of renal dysfunction. Cases were categorized into prerenal, renal, and post-renal causes of azotemia, on the basis of histologic and clinical criteria. The severity of azotemia varied within groups, but the mean value for degree of azotemia was lowest in the prerenal group. The BUN/SC ratios were highest when azotemia was mild, regardless of cause. The BUN/SC ratios in the 3 groups were not significantly different when the degree of azotemia was considered, indicating that differentiation of renal from extrarenal azotemia was not possible in the dog and cat, on the basis of relative values of BUN and SC. Comparison of BUN/SC ratios in acute and chronic azotemia of comparable magnitude revealed no significant differences between groups, indicating that this ratio cannot be used to differentiate acute and chronic azotemia. Following supportive therapy, BUN decreased significantly (P less than 0.05) more than SC, suggesting that extrarenal factors contributed to the increased BUN and that proportionately more urea than creatinine was excreted by the kidneys during therapy. The BUN/SC ratios varied widely and to a similar degree in all groups examined. Inasmuch as the BUN and SC were not correlated with more accurate measurements of renal function, conclusions could not be drawn concerning the superiority of either factor as a measure of renal function. Many nonrenal factors, previously identified, influence serum concentration of urea and creatinine. In recent studies involving azotemic human beings and rats, it was suggested that up to 25% of the urea and 65% of the creatinine produced in the body is degraded by enteric bacteria rather than excreted directly by the kidneys. These data indicate that neither BUN or SC can be used as precise tests of renal function, although SC is subject to alteration by fewer nonrenal factors than is BUN. In older medical and veterinary medical literature, the use of SC as a prognostic indicator had been advocated. Newer findings on the pathophysiology of creatininemia and retrospective case studies do not support this view. In the present study, severe creatininemia was documented in cases in which primary renal dysfunction did not exist. It was concluded that BUN and SC should continue to be regarded as crude indexes of renal function. Clinical value lies in the relative ease of their determination. Because of their lack of sensitivity, more specific evaluation of renal function (urine concentrating ability, phenolsulfonphthalein excretion) may be indicated when BUN and SC are normal or only slightly elevated. Because extrarenal factors may alter BUN and SC, it is necessary to correlate these values with clinical and other laboratory data to differentiate renal from extra-renal azotemia. Single determinations of BUN or SC provide no basis for prognosis."} {"id": "PMID:1270343", "title": "Tyzzer's disease in a dog.", "content": "A 5-week-old mixed-breed dog was examined because of emaciation and depression associated with chronic anorexia, diarrhea, and vomiting. Its rectal temperature was subnormal and it died on the day of admission. At necropsy, small focal lesions were distributed through the liver. Enteric alterations included catarrhal enteritis with fluid contents, excess production of mucus, and mucosal hyperemia. Microscopically, the hepatic lesions were disseminated foci of coagulative necrosis, with little or no associated inflammatory cell response. Numerous organisms morphologically consistent with Bacillus piliformis were demonstrated within viable hepatocytes at the periphery of the necrotic foci and in the intestinal mucosa. Numerous coccidial forms were found within the epithelial cells of the intestinal mucosa, which was focally necrotic.", "contents": "Tyzzer's disease in a dog. A 5-week-old mixed-breed dog was examined because of emaciation and depression associated with chronic anorexia, diarrhea, and vomiting. Its rectal temperature was subnormal and it died on the day of admission. At necropsy, small focal lesions were distributed through the liver. Enteric alterations included catarrhal enteritis with fluid contents, excess production of mucus, and mucosal hyperemia. Microscopically, the hepatic lesions were disseminated foci of coagulative necrosis, with little or no associated inflammatory cell response. Numerous organisms morphologically consistent with Bacillus piliformis were demonstrated within viable hepatocytes at the periphery of the necrotic foci and in the intestinal mucosa. Numerous coccidial forms were found within the epithelial cells of the intestinal mucosa, which was focally necrotic."} {"id": "PMID:1270378", "title": "Determination of melengestrol acetate in bovine tissue: collaborative study.", "content": "Seven laboratories collaboratively studied a method for the assay of melengestrol acetate at the 0, 10, and 20 ppb levels in bovine fat, liver, muscle, and kidney. The study included fortification of tissue by each laboratory and analysis of fat samples taken from treated heifers which had endogenous levels of 0, 10, and 20 ppb melengestrol acetate. The multistep cleanup procedure used included extraction, solvent partition, column chromatography, and electron capture gas-liquid chromatographic, determination. Results of the study for muscle, liver, kidney, and fat showed that the method gave satisfactory recoveries and accuracy. In fat, the most critical tissue, recovery was greater than 93%. A statistical comparison of the results reported for fat tissue from treated heifers demonstrated that 5 of the 7 laboratories obtained similar results. The results produced by the method can be expected to be repeatable within and among laboratories. On the basis of the collaborative results the method has been adopted as official first action.", "contents": "Determination of melengestrol acetate in bovine tissue: collaborative study. Seven laboratories collaboratively studied a method for the assay of melengestrol acetate at the 0, 10, and 20 ppb levels in bovine fat, liver, muscle, and kidney. The study included fortification of tissue by each laboratory and analysis of fat samples taken from treated heifers which had endogenous levels of 0, 10, and 20 ppb melengestrol acetate. The multistep cleanup procedure used included extraction, solvent partition, column chromatography, and electron capture gas-liquid chromatographic, determination. Results of the study for muscle, liver, kidney, and fat showed that the method gave satisfactory recoveries and accuracy. In fat, the most critical tissue, recovery was greater than 93%. A statistical comparison of the results reported for fat tissue from treated heifers demonstrated that 5 of the 7 laboratories obtained similar results. The results produced by the method can be expected to be repeatable within and among laboratories. On the basis of the collaborative results the method has been adopted as official first action."} {"id": "PMID:1270379", "title": "Appraisal of existing methodology in aspiration toxicity testing.", "content": "New methods or modifications of currently used methods in aspiration toxicology must be capable of accurately assessing the hazard and toxicity potentials of those products which are capable of being aspirated. The methods evaluated in the rat were intratracheal injections,intravenous injections, and modifications of the Gerarde technique. A product containing petroleum distillates and a standard viscosity petroleum distillate sample were administered to Osborne-Mendel rats, rabbits, and guinea pigs in ml/kg doses. The utility of the methods was determined by comparing lung weight increases, lung-body weight ratios, gross pathological lung changes, and mortality. The modified Gerarde technique showed the best potential for predicting aspiration hazard and toxicity based on the severity of the reactions which, using a radiolabeled oil, was shown to be a function of the amount of product which enters and reacts with the lungs. The influence of preventing the swallowing reflex to assure aspiration of the oil was assessed in the rat. The results show that less than 10% of the dose is aspirated when the swallowing reflex occurs. Methods of sacrifice were investigated for an effect on rat lung weight. No tested method except stunning with cervical dislocation produced an effect. Tests were conducted on rats and rabbits to determine differences in lung reactivity to the influence of inhalation anesthetics, pentothal sodium, or no anesthesia in response to petroleum distillate administration and to determine which test species is the better animal model. The resuls indicate that the rat is the better test model because of degree of lung reaction, size, and economy, and that inhalation anesthesia with ether is preferable over the other choices.", "contents": "Appraisal of existing methodology in aspiration toxicity testing. New methods or modifications of currently used methods in aspiration toxicology must be capable of accurately assessing the hazard and toxicity potentials of those products which are capable of being aspirated. The methods evaluated in the rat were intratracheal injections,intravenous injections, and modifications of the Gerarde technique. A product containing petroleum distillates and a standard viscosity petroleum distillate sample were administered to Osborne-Mendel rats, rabbits, and guinea pigs in ml/kg doses. The utility of the methods was determined by comparing lung weight increases, lung-body weight ratios, gross pathological lung changes, and mortality. The modified Gerarde technique showed the best potential for predicting aspiration hazard and toxicity based on the severity of the reactions which, using a radiolabeled oil, was shown to be a function of the amount of product which enters and reacts with the lungs. The influence of preventing the swallowing reflex to assure aspiration of the oil was assessed in the rat. The results show that less than 10% of the dose is aspirated when the swallowing reflex occurs. Methods of sacrifice were investigated for an effect on rat lung weight. No tested method except stunning with cervical dislocation produced an effect. Tests were conducted on rats and rabbits to determine differences in lung reactivity to the influence of inhalation anesthetics, pentothal sodium, or no anesthesia in response to petroleum distillate administration and to determine which test species is the better animal model. The resuls indicate that the rat is the better test model because of degree of lung reaction, size, and economy, and that inhalation anesthesia with ether is preferable over the other choices."} {"id": "PMID:1270380", "title": "Survey of food products for volatile N-nitrosamines.", "content": "A variety of food products containing nitrite were analyzed for 14 volatile N-nitrosamines by using a method demonstrated to be sensitive to 10 ppb. A total of 121 food samples were screened for volatile N-nitrosamine content. N-Nitrosopyrrolidine was confirmed in fried bacon at levels up to 139 ppb. N-Dimethylnitrosamine, N-nitrosopyrrolidine, and N-nitrosopiperidine were also confirmed in spice-cure mixtures at levels ranging from 50 to 2000 ppb.", "contents": "Survey of food products for volatile N-nitrosamines. A variety of food products containing nitrite were analyzed for 14 volatile N-nitrosamines by using a method demonstrated to be sensitive to 10 ppb. A total of 121 food samples were screened for volatile N-nitrosamine content. N-Nitrosopyrrolidine was confirmed in fried bacon at levels up to 139 ppb. N-Dimethylnitrosamine, N-nitrosopyrrolidine, and N-nitrosopiperidine were also confirmed in spice-cure mixtures at levels ranging from 50 to 2000 ppb."} {"id": "PMID:1270381", "title": "Determination of bergapten in fragrance preparations by thin layer chromatography and spectrophotofluorometry.", "content": "A method has been developed for the determination of bergapten (5-methoxypsoralen), a known phototoxin, in perfumes,colognes, and toilet waters. The bergapten and other lactonic compounds were first isolated from the sample by a series of extractions. The extract containing the bergapten was diluted to a known volume and a aliquot was spotted on a thin layer chromatographic (TLC) plate coated with silica gel G. After 2-dimensional development with hexane - carbon tetrachloride - tert - butylamine (180+12+9) and hexane-toluene-ethyl acetate-acetic acid (100+10+15+0.5), the TLC plate was dried and the emitted fluorescence of bergapten was measured, using a spectrophotofluorometer equipped with a TLC accessory and coupled to an automatic digital integrator. The amount of bergapten was determined by comparing its peak area to those of bergapten standards. The average recovery for levels of 0.001, 0.005, and 0.01% bergapten was 88%.", "contents": "Determination of bergapten in fragrance preparations by thin layer chromatography and spectrophotofluorometry. A method has been developed for the determination of bergapten (5-methoxypsoralen), a known phototoxin, in perfumes,colognes, and toilet waters. The bergapten and other lactonic compounds were first isolated from the sample by a series of extractions. The extract containing the bergapten was diluted to a known volume and a aliquot was spotted on a thin layer chromatographic (TLC) plate coated with silica gel G. After 2-dimensional development with hexane - carbon tetrachloride - tert - butylamine (180+12+9) and hexane-toluene-ethyl acetate-acetic acid (100+10+15+0.5), the TLC plate was dried and the emitted fluorescence of bergapten was measured, using a spectrophotofluorometer equipped with a TLC accessory and coupled to an automatic digital integrator. The amount of bergapten was determined by comparing its peak area to those of bergapten standards. The average recovery for levels of 0.001, 0.005, and 0.01% bergapten was 88%."} {"id": "PMID:1270382", "title": "Determination of polychlorinated dibenzo-p-dioxins and dibenzofurans in commercial pentachlorophenols by combined gas chromatography-mass spectrometry.", "content": "Samples of commercial pentachlorophenol (PCP) and its sodium salt (PCP-Na) were examined for the presence of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), using a rapid, highly specific method of analysis. Phenolic compounds are removed by alkaline extraction, and the neutral components are fractionated on an alumina minicolumn. After gas chromatographic separation, individual PCDDs and PCDFs are detected by mass fragmentography and their presence is confirmed by complete mass spectral analysis. While some samples had only low amounts of PCDDs and PCDFs, others contained much higher amounts of these components. PCP-Na samples showed the unexpected presence of a tetrachlorodibenzo-p-dioxin. Re-analysis of PCP and PCP-Na samples with high PCDD contents on a high-resolution glass capillary column showed the presence of 3 hexa- and the 2 heptachlorodibenzo-p-dioxins with nearly constant isomeric ratios.", "contents": "Determination of polychlorinated dibenzo-p-dioxins and dibenzofurans in commercial pentachlorophenols by combined gas chromatography-mass spectrometry. Samples of commercial pentachlorophenol (PCP) and its sodium salt (PCP-Na) were examined for the presence of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), using a rapid, highly specific method of analysis. Phenolic compounds are removed by alkaline extraction, and the neutral components are fractionated on an alumina minicolumn. After gas chromatographic separation, individual PCDDs and PCDFs are detected by mass fragmentography and their presence is confirmed by complete mass spectral analysis. While some samples had only low amounts of PCDDs and PCDFs, others contained much higher amounts of these components. PCP-Na samples showed the unexpected presence of a tetrachlorodibenzo-p-dioxin. Re-analysis of PCP and PCP-Na samples with high PCDD contents on a high-resolution glass capillary column showed the presence of 3 hexa- and the 2 heptachlorodibenzo-p-dioxins with nearly constant isomeric ratios."} {"id": "PMID:1270383", "title": "Qualitative tests for added coloring matter in meat products.", "content": "The rapid qualitative detection of coal tar dyes, chemicals added to color meat products, and some natural coloring materials was investigated through extraction and subsequent identification by spectrophotometric, paper chromatographic, and specific reaction techniques. These techniques will detect the presence of coal tar dyes, imidazole, histamine, histidine, cochineal, beet powder, annatto, alkanet, carotene, paprika, saffron, turmeric, and materials causing discoloration in meats.", "contents": "Qualitative tests for added coloring matter in meat products. The rapid qualitative detection of coal tar dyes, chemicals added to color meat products, and some natural coloring materials was investigated through extraction and subsequent identification by spectrophotometric, paper chromatographic, and specific reaction techniques. These techniques will detect the presence of coal tar dyes, imidazole, histamine, histidine, cochineal, beet powder, annatto, alkanet, carotene, paprika, saffron, turmeric, and materials causing discoloration in meats."} {"id": "PMID:1270384", "title": "Determination of vitamin B12 in dry feeds by atomic absorption spectrophotometry.", "content": "Vitamin B12 was determined in dry feeds by atomic absorption spectrophotometry (AAS). Samples containing B12 were extracted with an assay solution, 5 g EDTA was added to the filtrate, the pH was adjusted to 7 with NH4OH, and 5 g charcoal was added. The charcoal was removed by filtering through ashless paper which was then placed in a beaker and ashed at 600 degrees C. After dissolving the cobalt oxide from the ash in 5N HNO3, cobalt content was determined by using AAS. To determine mg B12/lb feed, ppm cobalt in the feed is multiplied by 10.43. The sensitivity of the proposed procedure is 1 mg vitamin B12/lb. The procedure is rapid and precise, and results compare favorably with AOAC method 43.109.", "contents": "Determination of vitamin B12 in dry feeds by atomic absorption spectrophotometry. Vitamin B12 was determined in dry feeds by atomic absorption spectrophotometry (AAS). Samples containing B12 were extracted with an assay solution, 5 g EDTA was added to the filtrate, the pH was adjusted to 7 with NH4OH, and 5 g charcoal was added. The charcoal was removed by filtering through ashless paper which was then placed in a beaker and ashed at 600 degrees C. After dissolving the cobalt oxide from the ash in 5N HNO3, cobalt content was determined by using AAS. To determine mg B12/lb feed, ppm cobalt in the feed is multiplied by 10.43. The sensitivity of the proposed procedure is 1 mg vitamin B12/lb. The procedure is rapid and precise, and results compare favorably with AOAC method 43.109."} {"id": "PMID:1270385", "title": "Relationship between the biological availability and solubility rate of reduced iron.", "content": "Solubility rate determinations were conducted on electrolytic iron and hydrogen reduced iron and carbonyl iron samples to study the correlation of biological availability and solubility. There was excellent correlation for the hydrogen reduced iron and electrolytic iron samples,. The carbonyl iron samples showed a direct relationship between solubility and bioavailability, but these data were not numerically equivalent to data from other types.", "contents": "Relationship between the biological availability and solubility rate of reduced iron. Solubility rate determinations were conducted on electrolytic iron and hydrogen reduced iron and carbonyl iron samples to study the correlation of biological availability and solubility. There was excellent correlation for the hydrogen reduced iron and electrolytic iron samples,. The carbonyl iron samples showed a direct relationship between solubility and bioavailability, but these data were not numerically equivalent to data from other types."} {"id": "PMID:1270386", "title": "A screening method for protein characterization and differentiation.", "content": "A circular paper chromatographic method was developed for the separation of the amino acids in proteins into 7 subgroups. Butanol-acetic acid water (4+1+1) was used as the developing solvent. Eluted ninhydrin-stained aminograms gave rise to graphic profiles or numerical indexes based on absorbance percentages. The profiles can be used to compare protein-containing samples. Twenty different samples were studied through 190 comparisons of graphic profiles and coefficients of correlation, with only 4% misleading results. The method showed excellent reproducibility for the identification or differentiation of proteins and has the advantage of being performed with low-priced apparatus and reagents.", "contents": "A screening method for protein characterization and differentiation. A circular paper chromatographic method was developed for the separation of the amino acids in proteins into 7 subgroups. Butanol-acetic acid water (4+1+1) was used as the developing solvent. Eluted ninhydrin-stained aminograms gave rise to graphic profiles or numerical indexes based on absorbance percentages. The profiles can be used to compare protein-containing samples. Twenty different samples were studied through 190 comparisons of graphic profiles and coefficients of correlation, with only 4% misleading results. The method showed excellent reproducibility for the identification or differentiation of proteins and has the advantage of being performed with low-priced apparatus and reagents."} {"id": "PMID:1270387", "title": "Semiautomated ring carrier to facilitate and expedite disinfectant testing by the AOAC use-dilution method.", "content": "The AOAC use-dilution test requires the replicate examination of a number of contaminated metal rings. Ten metal rings may be tested within the 20 min structure of the test. From a statistical and economical viewpoint, it would be highly desirable to increase the number of rings examined in a single test. A semiautomated ring carrier permits testing 200 rings within a 20 min test.", "contents": "Semiautomated ring carrier to facilitate and expedite disinfectant testing by the AOAC use-dilution method. The AOAC use-dilution test requires the replicate examination of a number of contaminated metal rings. Ten metal rings may be tested within the 20 min structure of the test. From a statistical and economical viewpoint, it would be highly desirable to increase the number of rings examined in a single test. A semiautomated ring carrier permits testing 200 rings within a 20 min test."} {"id": "PMID:1270388", "title": "Phosphorus pentoxide as a drying agent for bacterial culture extracts analyzed by gas-liquid chromatography.", "content": "The procedure for gas chromatographic analysis of metabolic products of microbial fermentation includes solvent extraction of the aqueous growth media, drying of the extract, and direct chromatographic analysis of the solvent. In this study, 2 drying agents, magnesium sulfate and phosphorus pentoxide, were compared. Both were effective in removing water; however, phosphorus pentoxide removed water more completely and at a faster rate than magnesium sulfate. When a thermal conductivity detector is used, it is important to completely remove water from the solvent to prevent interference with volatile acids and alcohols. When water is present, short-chain alcohols (C2-C5) are eluted together with the water, causing peak overlap and shoulder separations. Phosphorus pentoxide quickly and effectively removed water so that a baseline was established following the solvent front on the chromatogram. The use of phosphorus pentoxide is particularly advantageous for identification or fermentation studies on Clostridium and Propionibacterium when rapid identification is desired or when large numbers of cultures are to be tested.", "contents": "Phosphorus pentoxide as a drying agent for bacterial culture extracts analyzed by gas-liquid chromatography. The procedure for gas chromatographic analysis of metabolic products of microbial fermentation includes solvent extraction of the aqueous growth media, drying of the extract, and direct chromatographic analysis of the solvent. In this study, 2 drying agents, magnesium sulfate and phosphorus pentoxide, were compared. Both were effective in removing water; however, phosphorus pentoxide removed water more completely and at a faster rate than magnesium sulfate. When a thermal conductivity detector is used, it is important to completely remove water from the solvent to prevent interference with volatile acids and alcohols. When water is present, short-chain alcohols (C2-C5) are eluted together with the water, causing peak overlap and shoulder separations. Phosphorus pentoxide quickly and effectively removed water so that a baseline was established following the solvent front on the chromatogram. The use of phosphorus pentoxide is particularly advantageous for identification or fermentation studies on Clostridium and Propionibacterium when rapid identification is desired or when large numbers of cultures are to be tested."} {"id": "PMID:1270389", "title": "Lactic and succinic acid levels and refractive indices in the determinations of the age of eggs.", "content": "The increase in the concentration of lactic and succinic acid during storage was measured in an attempt to determine the age of eggs. The increase in succinic acid alone is not sufficient to indicate egg age. Although lactic acid concentrations increase more rapidly, the levels are still very low, the increase is not linear, and concentrations in fresh eggs vary widely. On the other hand, refractive indices showed a nearly linear correlation with age and very little variation between eggs. These measurements are reproducible and easy to perform and, with further study, should provide an alternative to the AOAC method.", "contents": "Lactic and succinic acid levels and refractive indices in the determinations of the age of eggs. The increase in the concentration of lactic and succinic acid during storage was measured in an attempt to determine the age of eggs. The increase in succinic acid alone is not sufficient to indicate egg age. Although lactic acid concentrations increase more rapidly, the levels are still very low, the increase is not linear, and concentrations in fresh eggs vary widely. On the other hand, refractive indices showed a nearly linear correlation with age and very little variation between eggs. These measurements are reproducible and easy to perform and, with further study, should provide an alternative to the AOAC method."} {"id": "PMID:1270390", "title": "Gas-liquid chromatographic analysis of ethephon and fenoprop residues in apples and their decline before and after harvest.", "content": "Ethephon (2-chloroethylphosphonic acid) and fenoprop (2-(2,4,5-trichlorophenoxy) propionic acid) may be determined in the same apple sample. After extraction with methanol, 2 separate methylation procedures were required to quantitatively convert each compound. Ethephon was esterified with diazomethane and analyzed by a flame photometric detector in the P-mode. Fenoprop was esterified with boron trifluoride/methanol and analyzed by electron capture gas chromatography. Average recoveries were about 95% at 0.05 ppm for both compounds. The limit of detection was 0.05 ppm for ethephon and 0.01 ppm for fenoprop in a 1 g sample. The persistence of both compounds before and after harvest was studied. Ethephon and fenoprop were applied simultaneously to apple trees at the recommended concentrations of 300 and 20 ppm, respectively. Ethephon residues averaged 1.6, 0.75, and 0.4 ppm at 2 hr, 10 days, and after washing at 13 days, respectively. The corresponding fenoprop residues were 0.70, 0.025, and 0.024 ppm.", "contents": "Gas-liquid chromatographic analysis of ethephon and fenoprop residues in apples and their decline before and after harvest. Ethephon (2-chloroethylphosphonic acid) and fenoprop (2-(2,4,5-trichlorophenoxy) propionic acid) may be determined in the same apple sample. After extraction with methanol, 2 separate methylation procedures were required to quantitatively convert each compound. Ethephon was esterified with diazomethane and analyzed by a flame photometric detector in the P-mode. Fenoprop was esterified with boron trifluoride/methanol and analyzed by electron capture gas chromatography. Average recoveries were about 95% at 0.05 ppm for both compounds. The limit of detection was 0.05 ppm for ethephon and 0.01 ppm for fenoprop in a 1 g sample. The persistence of both compounds before and after harvest was studied. Ethephon and fenoprop were applied simultaneously to apple trees at the recommended concentrations of 300 and 20 ppm, respectively. Ethephon residues averaged 1.6, 0.75, and 0.4 ppm at 2 hr, 10 days, and after washing at 13 days, respectively. The corresponding fenoprop residues were 0.70, 0.025, and 0.024 ppm."} {"id": "PMID:1270391", "title": "Mass spectra of sodium N-alkyl and N,N-dialkyl dithiocarbamates and some related compounds.", "content": "Electron impact mass spectra of 8 sodium alkyl and dialkyl dithiocarbamate salts are reported with the spectra of 2 dithiocarbamate zinc salts and N',N'-dimethyl-N,N-dimethylthiocarbamylsulfenamide. The investigated compounds all gave molecular ions, and generalized descriptions of their fragmentation behavior are presented.", "contents": "Mass spectra of sodium N-alkyl and N,N-dialkyl dithiocarbamates and some related compounds. Electron impact mass spectra of 8 sodium alkyl and dialkyl dithiocarbamate salts are reported with the spectra of 2 dithiocarbamate zinc salts and N',N'-dimethyl-N,N-dimethylthiocarbamylsulfenamide. The investigated compounds all gave molecular ions, and generalized descriptions of their fragmentation behavior are presented."} {"id": "PMID:1270392", "title": "Analysis pesticides by chemical derivatization. III. Gas chromatographic characteristics and conditions for the formation of pentafluorobenzyl derivatives of ten herbicidal acids.", "content": "The reaction conditions to form pentafluorobenzyl derivatives of 10 herbicidal acids, at pesticide residue levels, were studied. The optimum conditions were reaction at room temperature for at least 5 hr (or overnight), using potassium carbonate solution as catalyst. The gas chromatographic characteristics of these derivatives were also studied. Nine of 10 of these derivatives can be separated on an OV-101/OV-210 gas chromatographic column.", "contents": "Analysis pesticides by chemical derivatization. III. Gas chromatographic characteristics and conditions for the formation of pentafluorobenzyl derivatives of ten herbicidal acids. The reaction conditions to form pentafluorobenzyl derivatives of 10 herbicidal acids, at pesticide residue levels, were studied. The optimum conditions were reaction at room temperature for at least 5 hr (or overnight), using potassium carbonate solution as catalyst. The gas chromatographic characteristics of these derivatives were also studied. Nine of 10 of these derivatives can be separated on an OV-101/OV-210 gas chromatographic column."} {"id": "PMID:1270393", "title": "Gas-liquid chromatographic analysis and chemical confirmation of azodrin (monocrotophos) residues in strawberries.", "content": "A gas-liquid chromatographic (GLC) method is described for the analysis and confirmation of azodrin (monocrotophos, 3-(dimethoxyphosphinyl)-N-methyl-cis-crotonamide) residues in strawberrires. The strawberries are extracted with acetone, and the filtrate is partioned with a mixture of methylene chloride and petroleum ether followed by further extraction with methylene chloride. The organic phases are combined, dried with anhydrous sodium sulfate, and concentrated to a small volume for GLC analysis on a 3% OV-210 column with flame photometric detection. Identity of the compound is confirmed by chromatography on the same column after trifluoroacetylation of an aliquot of the strawberry extract. The detection limit is about 2 ppb. The types of strawberry samples analyzed were fresh, frozen, pureed, and jam.", "contents": "Gas-liquid chromatographic analysis and chemical confirmation of azodrin (monocrotophos) residues in strawberries. A gas-liquid chromatographic (GLC) method is described for the analysis and confirmation of azodrin (monocrotophos, 3-(dimethoxyphosphinyl)-N-methyl-cis-crotonamide) residues in strawberrires. The strawberries are extracted with acetone, and the filtrate is partioned with a mixture of methylene chloride and petroleum ether followed by further extraction with methylene chloride. The organic phases are combined, dried with anhydrous sodium sulfate, and concentrated to a small volume for GLC analysis on a 3% OV-210 column with flame photometric detection. Identity of the compound is confirmed by chromatography on the same column after trifluoroacetylation of an aliquot of the strawberry extract. The detection limit is about 2 ppb. The types of strawberry samples analyzed were fresh, frozen, pureed, and jam."} {"id": "PMID:1270394", "title": "Thin layer chromatography of parathion as paraoxon with cholinesterase inhibition detection.", "content": "A simple, sensitive, and rapid method is described for the quantitative estimation of ng amounts of parathion (O,O-diethyl O-p-nitrophenyl phosphorothioate) as paraoxon (O,O-diethyl O-p-nitrophenyl phosphate) on thin layer chromatograms. Paraoxon is detected by inhibition, using p-nitrobenzenediazonium fluoroborate as the chromogenic reagent. This chromogenic reagent is more sensitive than Fast Blue B or indoxyl acetate; 0.1 ng may be detected and amounts from 5 to 50 ng may be estimated. The method is a viable alternative to gas chromatographic analysis for parathion.", "contents": "Thin layer chromatography of parathion as paraoxon with cholinesterase inhibition detection. A simple, sensitive, and rapid method is described for the quantitative estimation of ng amounts of parathion (O,O-diethyl O-p-nitrophenyl phosphorothioate) as paraoxon (O,O-diethyl O-p-nitrophenyl phosphate) on thin layer chromatograms. Paraoxon is detected by inhibition, using p-nitrobenzenediazonium fluoroborate as the chromogenic reagent. This chromogenic reagent is more sensitive than Fast Blue B or indoxyl acetate; 0.1 ng may be detected and amounts from 5 to 50 ng may be estimated. The method is a viable alternative to gas chromatographic analysis for parathion."} {"id": "PMID:1270395", "title": "Determination of arsenic and selenium in foods by electroanalytical techniques.", "content": "Arsenic and selsnium are determined in foods be differential pulse polarography and cathodic stripping voltammetry. The sample is digested with nitric acid and magnesium nitrate and then dissolved in dilute hydrochloric acid. An aliquot is removed, the arsenic is chemically reduced to the trivalent state, and interferences are removed by ion exchange before polarography. Selenium is determined in a second aliquot by cathodic stripping voltammetry. Recoveries for both elements in several foods were from 90 to 110%. The relative standard deviations for arsenic at 5 ppm and selenium at 0.48 ppm were 5.8 and 7.3%, respectively.", "contents": "Determination of arsenic and selenium in foods by electroanalytical techniques. Arsenic and selsnium are determined in foods be differential pulse polarography and cathodic stripping voltammetry. The sample is digested with nitric acid and magnesium nitrate and then dissolved in dilute hydrochloric acid. An aliquot is removed, the arsenic is chemically reduced to the trivalent state, and interferences are removed by ion exchange before polarography. Selenium is determined in a second aliquot by cathodic stripping voltammetry. Recoveries for both elements in several foods were from 90 to 110%. The relative standard deviations for arsenic at 5 ppm and selenium at 0.48 ppm were 5.8 and 7.3%, respectively."} {"id": "PMID:1270396", "title": "Digestion of fish samples for mercury determination by flameless atomic absorption spectrophotometry.", "content": "Methods of digestion of fish samples for mercury determination by flameless atomic absorption spectrophotometry have been investigated. Digestion in Teflon bombs, Kjeldahl flasks, or borosilicate test tubes gives comparable precisions and mercury recoveries. Because of their cost and effect in limiting productivity, Teflon bombs were considered unnecessary for analysis of fish samples. Experiments with cooked and uncooked fish samples have confirmed that no appreciable loss of mercury occurs during baking 30 min at 170 degrees C.", "contents": "Digestion of fish samples for mercury determination by flameless atomic absorption spectrophotometry. Methods of digestion of fish samples for mercury determination by flameless atomic absorption spectrophotometry have been investigated. Digestion in Teflon bombs, Kjeldahl flasks, or borosilicate test tubes gives comparable precisions and mercury recoveries. Because of their cost and effect in limiting productivity, Teflon bombs were considered unnecessary for analysis of fish samples. Experiments with cooked and uncooked fish samples have confirmed that no appreciable loss of mercury occurs during baking 30 min at 170 degrees C."} {"id": "PMID:1270397", "title": "Determination of zearalenone in corn: collaborative study.", "content": "Corn samples spiked at levels of 100, 300, 1000, and 2000 mug zearalenone/kg were sent to 22 collaborators for analysis by the Eppley method. All samples were yellow corn except one white corn sample spiked at 2000 mug/kg. Results from 16 collaborators were statistically analyzed. Only 4 of 16 collaborators detected zearalenone in the sample containing 100 mu/kg, but 11 detected the toxin in the sample containing 300 mug/kg. Average recoveries from all samples were 129% at 300 mug/kg, 101% at 1000 mug/kg, and 88% at 2000 mug/kg. The between-laboratory coefficients of variation were 53.0% at 300 mug/kg, 38.2% at 1000 mug/kg, and 27.0% at 2000 mug/kg. Five naturally contaminated corn samples, one in triplicate, were also provided. The mean level of zearalenone in the naturally contaminated samples ranged from 431 to 7622 mug/kg. The mean coefficient of variation for all samples was 40.5%. Two collaborators measured quantities of zearalenone on thin layer chromatographic plates densitometrically. Their results were not included in the statistical analysis, but the results indicated that densitometric measurement, given proper dilutions of solutions, could be used. The method has been adopted as official first action.", "contents": "Determination of zearalenone in corn: collaborative study. Corn samples spiked at levels of 100, 300, 1000, and 2000 mug zearalenone/kg were sent to 22 collaborators for analysis by the Eppley method. All samples were yellow corn except one white corn sample spiked at 2000 mug/kg. Results from 16 collaborators were statistically analyzed. Only 4 of 16 collaborators detected zearalenone in the sample containing 100 mu/kg, but 11 detected the toxin in the sample containing 300 mug/kg. Average recoveries from all samples were 129% at 300 mug/kg, 101% at 1000 mug/kg, and 88% at 2000 mug/kg. The between-laboratory coefficients of variation were 53.0% at 300 mug/kg, 38.2% at 1000 mug/kg, and 27.0% at 2000 mug/kg. Five naturally contaminated corn samples, one in triplicate, were also provided. The mean level of zearalenone in the naturally contaminated samples ranged from 431 to 7622 mug/kg. The mean coefficient of variation for all samples was 40.5%. Two collaborators measured quantities of zearalenone on thin layer chromatographic plates densitometrically. Their results were not included in the statistical analysis, but the results indicated that densitometric measurement, given proper dilutions of solutions, could be used. The method has been adopted as official first action."} {"id": "PMID:1270398", "title": "Gas-liquid chromatographic determination of beta-asarone in wines and flavors.", "content": "Wine samples containing beta-asarone (cis-2,4,5-trimethoxy-l-propenylbenzene) are distilled; beta-asarone is extracted by hexane and then quantitatively determined by gas-liquid chromatography (GLC), using ethyl palmitate as the internal standard. The GLC procedure is rapid and yields precise and accurate results. Mass spectrometry confirmed the identity of the GLC peak as beta-asarone. The ultraviolet spectra of beta-asarone and its isomer were also determined.", "contents": "Gas-liquid chromatographic determination of beta-asarone in wines and flavors. Wine samples containing beta-asarone (cis-2,4,5-trimethoxy-l-propenylbenzene) are distilled; beta-asarone is extracted by hexane and then quantitatively determined by gas-liquid chromatography (GLC), using ethyl palmitate as the internal standard. The GLC procedure is rapid and yields precise and accurate results. Mass spectrometry confirmed the identity of the GLC peak as beta-asarone. The ultraviolet spectra of beta-asarone and its isomer were also determined."} {"id": "PMID:1270399", "title": "Infrared identification of maleic acid in pharmaceutical maleate salts.", "content": "Difficulties are encountered in the USP melting point identification test for maleic acid extracted from chlorpheniramine maleate. A general procedure is described for the isolation and infrared identification of the maleic acid moiety of pharmaceutical salts from drug substances or dosage forms. This procedure permits the concurrent infrared identification of the amine moiety.", "contents": "Infrared identification of maleic acid in pharmaceutical maleate salts. Difficulties are encountered in the USP melting point identification test for maleic acid extracted from chlorpheniramine maleate. A general procedure is described for the isolation and infrared identification of the maleic acid moiety of pharmaceutical salts from drug substances or dosage forms. This procedure permits the concurrent infrared identification of the amine moiety."} {"id": "PMID:1270400", "title": "Spectrophotometric analysis of alkaloids with picrolonic acid.", "content": "The spectroscopic characteristics of the interaction of alkaloids with picrolonic acid were studied. In solvents of low and intermediate polarity, the presence of alkaloids caused a red shift of the 322 nm band of nonionized picrolonic acid to 355 nm, corresponding to the anionic resonance band. There was also a considerable increase in absorptivity, which was dependent on both the basicity (pKa) and molar concentration of the alkaloid present. Arylamines, aromatic N-heterocycles, and alkaloids lacking an aliphatic amine moiety did not show observable shifts. The interaction was developed into a spectrophotometric assay for the following alkaloids in pharmaceutical preparations: atropine, ephedrine, codeine, emetine, quinine, and strychnine. The method is sensitive to 2 mug alkaloid/ml, with an accuracy of not equal to 1.5% and a standard deviation of not equal to 1.05 - 1.31%.", "contents": "Spectrophotometric analysis of alkaloids with picrolonic acid. The spectroscopic characteristics of the interaction of alkaloids with picrolonic acid were studied. In solvents of low and intermediate polarity, the presence of alkaloids caused a red shift of the 322 nm band of nonionized picrolonic acid to 355 nm, corresponding to the anionic resonance band. There was also a considerable increase in absorptivity, which was dependent on both the basicity (pKa) and molar concentration of the alkaloid present. Arylamines, aromatic N-heterocycles, and alkaloids lacking an aliphatic amine moiety did not show observable shifts. The interaction was developed into a spectrophotometric assay for the following alkaloids in pharmaceutical preparations: atropine, ephedrine, codeine, emetine, quinine, and strychnine. The method is sensitive to 2 mug alkaloid/ml, with an accuracy of not equal to 1.5% and a standard deviation of not equal to 1.05 - 1.31%."} {"id": "PMID:1270401", "title": "Spectrophotometric determination of allylisothiocyanate in mustard seed oil.", "content": "Allylisothiocyanate is determined spectrophotometrically after reaction with 2,3-dichloro-1,4-naphthoquinone. For pure samples, the color intensity is proportional to allylisothiocyanate content in the range 0.8-3.0 mg/ml reaction mixture. A modified procedure is used to estimate allylisothiocyanate content of mustard seed oil. The reaction is linear for allylisothiocyanate concentrations in the range 40-240 mug/ml reaction mixture. Two mustard seed oil samples contained 0.995 not equal to 0.020 and 0.981 not equal to 0.019% allylisothiocyanate.", "contents": "Spectrophotometric determination of allylisothiocyanate in mustard seed oil. Allylisothiocyanate is determined spectrophotometrically after reaction with 2,3-dichloro-1,4-naphthoquinone. For pure samples, the color intensity is proportional to allylisothiocyanate content in the range 0.8-3.0 mg/ml reaction mixture. A modified procedure is used to estimate allylisothiocyanate content of mustard seed oil. The reaction is linear for allylisothiocyanate concentrations in the range 40-240 mug/ml reaction mixture. Two mustard seed oil samples contained 0.995 not equal to 0.020 and 0.981 not equal to 0.019% allylisothiocyanate."} {"id": "PMID:1270402", "title": "High-speed liquid chromatographic determination of phenothiazine in commercial pesticide formulations.", "content": "Phenothiazine (thiodiphenylamine) in commercial pesticide formulations is analyzed by high-speed liquid chromatography and ultraviolet absorption detection. Phenothiazine is extracted from the formulation with methanol and injected into the liquid chromatograph. Methanol-water (1+1) is the mobile phase. The amount of phenothiazine is calculated from peak height ratios. The liquid chromatographic procedure is much faster than the infrared or colorimetric method and yields values in close agreement with both of these methods.", "contents": "High-speed liquid chromatographic determination of phenothiazine in commercial pesticide formulations. Phenothiazine (thiodiphenylamine) in commercial pesticide formulations is analyzed by high-speed liquid chromatography and ultraviolet absorption detection. Phenothiazine is extracted from the formulation with methanol and injected into the liquid chromatograph. Methanol-water (1+1) is the mobile phase. The amount of phenothiazine is calculated from peak height ratios. The liquid chromatographic procedure is much faster than the infrared or colorimetric method and yields values in close agreement with both of these methods."} {"id": "PMID:1270403", "title": "Derivatization procedure for identification of aflatoxin M1 on a thin layer chromatogram.", "content": "A commodity extract containing presumptive aflatoxin M1 is placed on an origin spot of a thin layer chromatographic plate and overspotted with trifluoroacetic acid. The mixture is held in the dark 30 min at ambient temperature and then 30 min at 55 degrees C. The plate is developed with CHCL3-acetone-2-propanol (85+10+7). The Rf values of reacted and unreacted aflatoxin M1 are compared with authentic M1 similarly treated for identification. The lowest concentration that has been identified is 0.1 mug/kg.", "contents": "Derivatization procedure for identification of aflatoxin M1 on a thin layer chromatogram. A commodity extract containing presumptive aflatoxin M1 is placed on an origin spot of a thin layer chromatographic plate and overspotted with trifluoroacetic acid. The mixture is held in the dark 30 min at ambient temperature and then 30 min at 55 degrees C. The plate is developed with CHCL3-acetone-2-propanol (85+10+7). The Rf values of reacted and unreacted aflatoxin M1 are compared with authentic M1 similarly treated for identification. The lowest concentration that has been identified is 0.1 mug/kg."} {"id": "PMID:1270404", "title": "Beta-glycosidases and diabetic microangiopathy. II. An insulin-dependent isozyme of beta-N-acetylglucosaminidase.", "content": "Previously we reported that beta-glycosidase activities were markedly decreased in the kidney but increased in the serum of diabetic rats. To examine these changes, the isozymes of beta-N-acetylglucosaminidase [EC 3.2.1.30] of rats were examined by DEAE-cellulose column chromatography. At least 3 major isozymes were found in both the kidney and liver. The main isozyme was type II isozyme in normal rat kidney and type III in normal rat liver. The activity of the type II isozyme in the kidney was markedly lowered when the total activity was decreased in diabetes and its normal activity was restored on insulin treatment, in parallel with increase in the total activity in diabetes. No significant change was found in the chromatographic pattern of isozymes in the liver in diabetes. In diabetic rat serum, the increase of total activity was found to be due to increase of type I and II isozymes.", "contents": "Beta-glycosidases and diabetic microangiopathy. II. An insulin-dependent isozyme of beta-N-acetylglucosaminidase. Previously we reported that beta-glycosidase activities were markedly decreased in the kidney but increased in the serum of diabetic rats. To examine these changes, the isozymes of beta-N-acetylglucosaminidase [EC 3.2.1.30] of rats were examined by DEAE-cellulose column chromatography. At least 3 major isozymes were found in both the kidney and liver. The main isozyme was type II isozyme in normal rat kidney and type III in normal rat liver. The activity of the type II isozyme in the kidney was markedly lowered when the total activity was decreased in diabetes and its normal activity was restored on insulin treatment, in parallel with increase in the total activity in diabetes. No significant change was found in the chromatographic pattern of isozymes in the liver in diabetes. In diabetic rat serum, the increase of total activity was found to be due to increase of type I and II isozymes."} {"id": "PMID:1270405", "title": "Wound-induced phenylalanine ammonia-lyase in potato tuber tissue. Development of enzyme activity and effects of antibiotics.", "content": "Phenylalanine ammonia-lyase [EC 4.3.1.5.] activity increased rapidly after a 3-hr lag period in potato tuber (Solanum tuberosum L. cv. May Queen) disks incubated in a suitable medium in the dark at 25 degrees. The activity reached a maxinum after incubation for about 40 hr. The effects of actinomycin D, 6-methylpurine, cycloheximide, chloramphenicol, and mitomycin C on the induction of phenylalanine ammonia-lyase were investigated during incubation of the disks. Actinomycin D, 6-methylpurine, and cycloheximide all inhibited the formation of phenylalanine ammonia-lyase, though cycloheximide was the most effective at low concentrations. Application of actinomycin D for the initial lag period (3 hr) caused strong inhibition; however, if it was supplied later it did not inhibit but actually increased phenylalanine ammonialyase formation. In contrast, cycloheximide was effective over most of the incubation period. Chloramphenicol and mitomycin C did not inhibit phenylalanine phenylalanine ammonialyase induction, but markedly stimulated it. Light was not an essential factor for phenylalanine ammonia-lyase induction in the wounded tissue.", "contents": "Wound-induced phenylalanine ammonia-lyase in potato tuber tissue. Development of enzyme activity and effects of antibiotics. Phenylalanine ammonia-lyase [EC 4.3.1.5.] activity increased rapidly after a 3-hr lag period in potato tuber (Solanum tuberosum L. cv. May Queen) disks incubated in a suitable medium in the dark at 25 degrees. The activity reached a maxinum after incubation for about 40 hr. The effects of actinomycin D, 6-methylpurine, cycloheximide, chloramphenicol, and mitomycin C on the induction of phenylalanine ammonia-lyase were investigated during incubation of the disks. Actinomycin D, 6-methylpurine, and cycloheximide all inhibited the formation of phenylalanine ammonia-lyase, though cycloheximide was the most effective at low concentrations. Application of actinomycin D for the initial lag period (3 hr) caused strong inhibition; however, if it was supplied later it did not inhibit but actually increased phenylalanine ammonialyase formation. In contrast, cycloheximide was effective over most of the incubation period. Chloramphenicol and mitomycin C did not inhibit phenylalanine phenylalanine ammonialyase induction, but markedly stimulated it. Light was not an essential factor for phenylalanine ammonia-lyase induction in the wounded tissue."} {"id": "PMID:1270406", "title": "Biosynthesis of sulfated glycoprotein in the endometrium of rabbit uterus.", "content": "The endometrial scrapings obtained from the uteri of estrogen-treated rabbits were incubated with N-acetyl-d[1-3H]glucosamine and [35S]sulfate, and then the incubation medium (M-Fr) was separated from the tissue. The tissue was subsequently homogenized exhaustively in 0.25m sucrose, and the insoluble residue (R-Fr) was separate. The supernatant at 8,500Xg for 10 min of the homogenate was subjected to subcelular fractionation by discontinuous sucrose gradient ultracentrifugation, and a thiamine pyrophosphatase-rich fraction (g-fr) was obtained. Complex carbohydrates were then separated from M-Fr, R-Fr, and G-Fr. The radioactivities incorporated into these complex carbohydrates suggested that sulfated glycoprotein synthesized in G-Fr was secreted into M-Fr. In order to confirm the above observation, labelled sulfated glycoprotein was isolated from the incubation medium. Subsequently, N-ACETYL-D[1-3H]glucosamine was incorporated into N-acetylglucosamine residues and [35S]sulfate into sulfates located most probably at the 6-position of N-acetylglucosamine residues of sulfated glycoprotein.", "contents": "Biosynthesis of sulfated glycoprotein in the endometrium of rabbit uterus. The endometrial scrapings obtained from the uteri of estrogen-treated rabbits were incubated with N-acetyl-d[1-3H]glucosamine and [35S]sulfate, and then the incubation medium (M-Fr) was separated from the tissue. The tissue was subsequently homogenized exhaustively in 0.25m sucrose, and the insoluble residue (R-Fr) was separate. The supernatant at 8,500Xg for 10 min of the homogenate was subjected to subcelular fractionation by discontinuous sucrose gradient ultracentrifugation, and a thiamine pyrophosphatase-rich fraction (g-fr) was obtained. Complex carbohydrates were then separated from M-Fr, R-Fr, and G-Fr. The radioactivities incorporated into these complex carbohydrates suggested that sulfated glycoprotein synthesized in G-Fr was secreted into M-Fr. In order to confirm the above observation, labelled sulfated glycoprotein was isolated from the incubation medium. Subsequently, N-ACETYL-D[1-3H]glucosamine was incorporated into N-acetylglucosamine residues and [35S]sulfate into sulfates located most probably at the 6-position of N-acetylglucosamine residues of sulfated glycoprotein."} {"id": "PMID:1270407", "title": "The role of C1 esterase inhibitor in the activation of C1r, a subcomponent of the first component of complement from human plasma.", "content": "Clr was isolated from human serum by DEAE-cellulose column chromatography in the presence of EDTA. The isolated Clr did not hydrolyze N(alpha)-acetyl-L-arginine methyl ester, unless activated by brief treatment with trypsin [EC 3.4.21.4]. On thecolumn, the C1 esterase inhibitor activity was found to coincide with Clr but not C1s (another subcomponent of the first component) C1r was isolated from the euglobulin fraction of human serum by DEAE-cellulose column chromatograph. On Sephadex G-200 column chromatography, Clr was eluted in the void volume, whereas Clr was eluted in a position corresponding to a molecular weight of 140,000-160,000. The results indicated that, on activation, Clr was converted to an enzyme of lower molecular weight...", "contents": "The role of C1 esterase inhibitor in the activation of C1r, a subcomponent of the first component of complement from human plasma. Clr was isolated from human serum by DEAE-cellulose column chromatography in the presence of EDTA. The isolated Clr did not hydrolyze N(alpha)-acetyl-L-arginine methyl ester, unless activated by brief treatment with trypsin [EC 3.4.21.4]. On thecolumn, the C1 esterase inhibitor activity was found to coincide with Clr but not C1s (another subcomponent of the first component) C1r was isolated from the euglobulin fraction of human serum by DEAE-cellulose column chromatograph. On Sephadex G-200 column chromatography, Clr was eluted in the void volume, whereas Clr was eluted in a position corresponding to a molecular weight of 140,000-160,000. The results indicated that, on activation, Clr was converted to an enzyme of lower molecular weight..."} {"id": "PMID:1270408", "title": "Isolation and characterization of calcitonin from pericardium and esophagus of eel.", "content": "Calcitonin was extracted from the pericardium and esophagus of eel in quantities sufficient to permit purification and chemical characterization. Homogeneous calcitonin could be isolated by a six-step fractionation starting from acetone powder of the organs. The fractionation procedure consisted of acid extraction, gel filtration on Sephadex G-75, chromatography on SP-Sephadex C-25, gel filtration on the Sephadex G-50, chromatography on carboxymethylcellulose, and gel filtration on Sephadex G-50. Fractionation of the hormone was monitored by assay of its biological activity and from its behaviour on thin layer chromatography and polyacrylamide gel disc electrophoresis. The hormone contained 32 amino acid residues, like calcitonins from other species of animals, but its amino acid composition was different from those of previously characterized hormones. Eel calcitonin possessed almost the same, or higher, biological activity as the salmon or chicken hormone, which show the highest specific activity among calcitonins so far isolated.", "contents": "Isolation and characterization of calcitonin from pericardium and esophagus of eel. Calcitonin was extracted from the pericardium and esophagus of eel in quantities sufficient to permit purification and chemical characterization. Homogeneous calcitonin could be isolated by a six-step fractionation starting from acetone powder of the organs. The fractionation procedure consisted of acid extraction, gel filtration on Sephadex G-75, chromatography on SP-Sephadex C-25, gel filtration on the Sephadex G-50, chromatography on carboxymethylcellulose, and gel filtration on Sephadex G-50. Fractionation of the hormone was monitored by assay of its biological activity and from its behaviour on thin layer chromatography and polyacrylamide gel disc electrophoresis. The hormone contained 32 amino acid residues, like calcitonins from other species of animals, but its amino acid composition was different from those of previously characterized hormones. Eel calcitonin possessed almost the same, or higher, biological activity as the salmon or chicken hormone, which show the highest specific activity among calcitonins so far isolated."} {"id": "PMID:1270409", "title": "Binding of retinol-binding protein obtained from human urine with vitamin A derivatives and terpenoids.", "content": "Retinol-binding protein(RBP) was purified from fresh urine of patients suffering from Itai-Itai disease. The purified preparation contained two types of apo-RBP(Apo I and II) in equal amounts as major components (about 85% of the total RBP). The corresponding two retinol-binding forms (Holo I and II) were present as minor components (about 15% of the total)...", "contents": "Binding of retinol-binding protein obtained from human urine with vitamin A derivatives and terpenoids. Retinol-binding protein(RBP) was purified from fresh urine of patients suffering from Itai-Itai disease. The purified preparation contained two types of apo-RBP(Apo I and II) in equal amounts as major components (about 85% of the total RBP). The corresponding two retinol-binding forms (Holo I and II) were present as minor components (about 15% of the total)..."} {"id": "PMID:1270410", "title": "Amino acid sequence of an active fragment of potato proteinase inhibitor IIa.", "content": "The complete amino acid sequence of an active fragment of potato proteinase inhibitor IIa has been established by the Edman degradation procedure and the carboxypeptidase technique. Sequence analyses were carried out on the reduced and carboxymethylated active fragment and its tryptic peptides. To aid in the alignment of some tryptic peptides, the partial sequences of two fragments obtained by selective tryptic cleavage of the reactive site peptide bond of inhibitor IIa at acidic pH, with subsequent reduction and carboxymethylation, were also analyzed. The active fragment consisted of 45 amino acid residues including 6 half-cystine residues. Degradation of the intact active fragment by subtilisin [EC 3.4.21.14.] at pH 6.5. yielded 3 cystine-containing peptides. Sequence analyses of these peptides revealed that the 3 disulfide linkages were located between Cys(10) and Cys(24), Cys(14) and Cys(35), and Cys(20) and Cys(43). The reactive site peptide bond of inhibitor IIa, a Lys-Ser bond, was located between positions 32 and 33 of the active fragment. The overall sequence of the active fragment was quite different from those of potato chymotrypsin inhibitor I (subunit A) and potato carboxypeptidase inhibitor.", "contents": "Amino acid sequence of an active fragment of potato proteinase inhibitor IIa. The complete amino acid sequence of an active fragment of potato proteinase inhibitor IIa has been established by the Edman degradation procedure and the carboxypeptidase technique. Sequence analyses were carried out on the reduced and carboxymethylated active fragment and its tryptic peptides. To aid in the alignment of some tryptic peptides, the partial sequences of two fragments obtained by selective tryptic cleavage of the reactive site peptide bond of inhibitor IIa at acidic pH, with subsequent reduction and carboxymethylation, were also analyzed. The active fragment consisted of 45 amino acid residues including 6 half-cystine residues. Degradation of the intact active fragment by subtilisin [EC 3.4.21.14.] at pH 6.5. yielded 3 cystine-containing peptides. Sequence analyses of these peptides revealed that the 3 disulfide linkages were located between Cys(10) and Cys(24), Cys(14) and Cys(35), and Cys(20) and Cys(43). The reactive site peptide bond of inhibitor IIa, a Lys-Ser bond, was located between positions 32 and 33 of the active fragment. The overall sequence of the active fragment was quite different from those of potato chymotrypsin inhibitor I (subunit A) and potato carboxypeptidase inhibitor."} {"id": "PMID:1270411", "title": "Phospholipid metabolism in Ehrlich ascites tumor cells. I. Turnover rate of phosphatidylinositol.", "content": "1. Radioactive precursors, 32 PI, [1-14C]glycerol, and [1-14C]acetate, were individually injected into the peritoneal cavity of mice bearing Ehrlich ascites tumor, and the rates of incorporation into phospholipid fraction of Ehrlich ascites tumor cells were estimated. Although no distinct difference in specific activities was observed between phosphatidylinositol and other phospholipid classes as regards the incorporation of [1-14C]acetate of [1-14C]glycerol, a higher rate of incorporation of 32Pi into phosphatidylinositol was observed. The specific activity of phosphatidylinositol reached more than ten times that of phosphatidylcholine in the first hour. 2. The radioactivities incorporated into the phospholipids of Ehrlich ascites tumor cells and liver were estimated after simultaneous injection 32Pi and [2-3H]inositol. The incorporation of 32Pi into phosphatidylinositol of liver was similar in specific activity to those of other phospholipids. The ratio (3H/32Pi) of phosphatidylinositol only slightly in the ascites tumor cells, while an appreciable decrease of the ratio was observed in the liver during the first 3 hr. 3. These results suggest that phosphatidylinositol synthesis through pathways other than de novo synthesis is rapid in ascites tumor cells.", "contents": "Phospholipid metabolism in Ehrlich ascites tumor cells. I. Turnover rate of phosphatidylinositol. 1. Radioactive precursors, 32 PI, [1-14C]glycerol, and [1-14C]acetate, were individually injected into the peritoneal cavity of mice bearing Ehrlich ascites tumor, and the rates of incorporation into phospholipid fraction of Ehrlich ascites tumor cells were estimated. Although no distinct difference in specific activities was observed between phosphatidylinositol and other phospholipid classes as regards the incorporation of [1-14C]acetate of [1-14C]glycerol, a higher rate of incorporation of 32Pi into phosphatidylinositol was observed. The specific activity of phosphatidylinositol reached more than ten times that of phosphatidylcholine in the first hour. 2. The radioactivities incorporated into the phospholipids of Ehrlich ascites tumor cells and liver were estimated after simultaneous injection 32Pi and [2-3H]inositol. The incorporation of 32Pi into phosphatidylinositol of liver was similar in specific activity to those of other phospholipids. The ratio (3H/32Pi) of phosphatidylinositol only slightly in the ascites tumor cells, while an appreciable decrease of the ratio was observed in the liver during the first 3 hr. 3. These results suggest that phosphatidylinositol synthesis through pathways other than de novo synthesis is rapid in ascites tumor cells."} {"id": "PMID:1270412", "title": "Changes in ornithine decarboxylase activity in normal tissues of tumor-bearing mice during tumor growth.", "content": "The ornithine decarboxylase [EC 4.1.1.17] activities in the liver and spleen of tumor-bearing mice increased remarkably, reaching a peak 4 to 6 days after inoculation of tumor cells. On the contrary, the enzyme activity in the kidney decreased during tumor growth and had almost disappeared on day 6 after tumor inoculation. Injection of cell-free tumor homogenate also raised the enzyme activities in the liver and spleen, but did not change the activity in the kidney. No increase in enzyme activity in the liver of mice was observed on injection of homogenates of normal tissues, such as liver, spleen, kidney, and muscle.", "contents": "Changes in ornithine decarboxylase activity in normal tissues of tumor-bearing mice during tumor growth. The ornithine decarboxylase [EC 4.1.1.17] activities in the liver and spleen of tumor-bearing mice increased remarkably, reaching a peak 4 to 6 days after inoculation of tumor cells. On the contrary, the enzyme activity in the kidney decreased during tumor growth and had almost disappeared on day 6 after tumor inoculation. Injection of cell-free tumor homogenate also raised the enzyme activities in the liver and spleen, but did not change the activity in the kidney. No increase in enzyme activity in the liver of mice was observed on injection of homogenates of normal tissues, such as liver, spleen, kidney, and muscle."} {"id": "PMID:1270413", "title": "Subunit structure of AMP-deaminase from chicken and rabbit skeletal muscle.", "content": "The AMP-deaminases from chicken and rabbit muscle have been investigated by techniques which include sedimentation equilibrium, sodium dodecyl sulfate gel electrophoresis, amino acid analysis, NH2- and COOH-terminal analyses, and tryptic peptide mapping. The molecular weights of the native chicken (276,000) and rabbit (271,000) enzymes obtained by sedimentation equilibrium studies are in good agreement with values of 276,000 (chicken) and 275,000 (rabbit) calculated from amino acid analyses. The enzymes were reduced, carboxymethylated, and treated with either maleic or succinic anhydride in the presence of 6 M guanidine hydrochloride. Sodium dodecyl sulfate gel electrophoresis of the chemically modified enzymes resulted in a single electrophoretic species having an apparent molecular weight of 85,000. This observation is consistent with previous studies on the nonacylated enzymes and suggests that the muscle AMP-deaminases from chicken and rabbit do not contain noncovalent linkages which are readily disrupted by a large increase in negative charge. NH2-terminal analyses by the method of Stark and Amyth as well as the dansyl technique, indicate that the NH2-terminal positions of these enzymes are blocked. The enzymes are also resistant to digestion with carboxypeptidases A or B (or both) in the presence of sodium dodecyl sulfate. The most distinctive feature of the amino acid compositions of both the chicken and rabbit AMP-deaminases is the presende of eight half-cystine residues per 69,000 g of protein. Tryptic digests of the S-14C-carboxymethylated proteins were fractionated by ion exchange chromatography and high voltage electrophoresis. Six and five radioactiviely labeled peptides were detected in the electrophoretograms of the chicken and rabbit enzymes, respectively. This observation and the number of ninhydrinposition spots, together with the physical data on the molecular weights of the native enzymes and their subunits, suggest that the AMP-deaminases from chidken and rabbit muscle consist of four identical or very similar polypeptide chains.", "contents": "Subunit structure of AMP-deaminase from chicken and rabbit skeletal muscle. The AMP-deaminases from chicken and rabbit muscle have been investigated by techniques which include sedimentation equilibrium, sodium dodecyl sulfate gel electrophoresis, amino acid analysis, NH2- and COOH-terminal analyses, and tryptic peptide mapping. The molecular weights of the native chicken (276,000) and rabbit (271,000) enzymes obtained by sedimentation equilibrium studies are in good agreement with values of 276,000 (chicken) and 275,000 (rabbit) calculated from amino acid analyses. The enzymes were reduced, carboxymethylated, and treated with either maleic or succinic anhydride in the presence of 6 M guanidine hydrochloride. Sodium dodecyl sulfate gel electrophoresis of the chemically modified enzymes resulted in a single electrophoretic species having an apparent molecular weight of 85,000. This observation is consistent with previous studies on the nonacylated enzymes and suggests that the muscle AMP-deaminases from chicken and rabbit do not contain noncovalent linkages which are readily disrupted by a large increase in negative charge. NH2-terminal analyses by the method of Stark and Amyth as well as the dansyl technique, indicate that the NH2-terminal positions of these enzymes are blocked. The enzymes are also resistant to digestion with carboxypeptidases A or B (or both) in the presence of sodium dodecyl sulfate. The most distinctive feature of the amino acid compositions of both the chicken and rabbit AMP-deaminases is the presende of eight half-cystine residues per 69,000 g of protein. Tryptic digests of the S-14C-carboxymethylated proteins were fractionated by ion exchange chromatography and high voltage electrophoresis. Six and five radioactiviely labeled peptides were detected in the electrophoretograms of the chicken and rabbit enzymes, respectively. This observation and the number of ninhydrinposition spots, together with the physical data on the molecular weights of the native enzymes and their subunits, suggest that the AMP-deaminases from chidken and rabbit muscle consist of four identical or very similar polypeptide chains."} {"id": "PMID:1270414", "title": "Leucine 2,3-aminomutase, an enzyme of leucine catabolism.", "content": "The initial step in the fermentation of leucine to acetate, isobutyrate, and ammonia by Clostridium sporogenes is the B12 coenzyme-dependent conversion of alpha-leucine to beta-leucine (3-amino-4-methylpentanoate). The amino group migration reaction, catalyzed by leucine 2,3-aminomutase, is reversible and is inhibited by intrinsic factor. The enzyme activity has been found in several clostridia, in rat, sheep, rhesus, and African green monkey livers, and in human leukocytes.", "contents": "Leucine 2,3-aminomutase, an enzyme of leucine catabolism. The initial step in the fermentation of leucine to acetate, isobutyrate, and ammonia by Clostridium sporogenes is the B12 coenzyme-dependent conversion of alpha-leucine to beta-leucine (3-amino-4-methylpentanoate). The amino group migration reaction, catalyzed by leucine 2,3-aminomutase, is reversible and is inhibited by intrinsic factor. The enzyme activity has been found in several clostridia, in rat, sheep, rhesus, and African green monkey livers, and in human leukocytes."} {"id": "PMID:1270415", "title": "Primary structure of streptococcal proteinase. I Isolation, composition, and amino acid sequences of the tryptic and chymotryptic peptides of cyanogen bromide fragments 1 to 4.", "content": "Tryptic and chymotroptic peptides were isolated and characterized from cyanogen bromide fragments 1 to 4 of streptococcal proteinase and subjected to sequence analysis by the Edman degradation, carboxy-peptidase digestion, and hydrolytic regeneration of the amino acid residues from the phenylthiocarbamyl derivatives. The results, together with the sequence data of the cyanogen bromide fragment 5 reported in the accompanying papers, provide the structural formula of streptococcal proteinase.", "contents": "Primary structure of streptococcal proteinase. I Isolation, composition, and amino acid sequences of the tryptic and chymotryptic peptides of cyanogen bromide fragments 1 to 4. Tryptic and chymotroptic peptides were isolated and characterized from cyanogen bromide fragments 1 to 4 of streptococcal proteinase and subjected to sequence analysis by the Edman degradation, carboxy-peptidase digestion, and hydrolytic regeneration of the amino acid residues from the phenylthiocarbamyl derivatives. The results, together with the sequence data of the cyanogen bromide fragment 5 reported in the accompanying papers, provide the structural formula of streptococcal proteinase."} {"id": "PMID:1270416", "title": "Primary structure of streptococcal proteinase. II. Isolation, composition, and amino acid sequences of the tryptic and chymotryptic peptides of cyanogen bromide fragment 5.", "content": "The amino acid sequence of the cyanogen bromide fragment 5 of streptococcal proteinase has been determined. This fragment comprises residues 130 to 253 of the proteinase chain. Six tryptic peptides were isolated from maleylated cyanogen bromide fragment 5, and their alignment was obtained by the overlap of chymotryptic peptides. Sequence analysis of tryptic, chymotryptic, and thermolysin peptides was performed by the 5-deimethylaminoaphthalene-1-sulfonyl technique and carboxypeptidases digestion.", "contents": "Primary structure of streptococcal proteinase. II. Isolation, composition, and amino acid sequences of the tryptic and chymotryptic peptides of cyanogen bromide fragment 5. The amino acid sequence of the cyanogen bromide fragment 5 of streptococcal proteinase has been determined. This fragment comprises residues 130 to 253 of the proteinase chain. Six tryptic peptides were isolated from maleylated cyanogen bromide fragment 5, and their alignment was obtained by the overlap of chymotryptic peptides. Sequence analysis of tryptic, chymotryptic, and thermolysin peptides was performed by the 5-deimethylaminoaphthalene-1-sulfonyl technique and carboxypeptidases digestion."} {"id": "PMID:1270417", "title": "Primary structure of streptococcal proteinase. III. Isolation of cyanogen bromide peptides: complete covalent structure of the polypeptide chain.", "content": "The following sequence has been derived for streptococcal proteinase. (See article). The sequence permits the assignment of the single cysteine residue essential for catalytic action at position 47 from the NH2 terminus of the protein. The tryptophan residue at the binding site of the enzyme is at position 214. A histidine residue at position 195 has been assigned as the catalytically important entity in the molecule. Streptococcal proteinase and papain, an enzyme with similar properties, are compared with respect to structure and function.", "contents": "Primary structure of streptococcal proteinase. III. Isolation of cyanogen bromide peptides: complete covalent structure of the polypeptide chain. The following sequence has been derived for streptococcal proteinase. (See article). The sequence permits the assignment of the single cysteine residue essential for catalytic action at position 47 from the NH2 terminus of the protein. The tryptophan residue at the binding site of the enzyme is at position 214. A histidine residue at position 195 has been assigned as the catalytically important entity in the molecule. Streptococcal proteinase and papain, an enzyme with similar properties, are compared with respect to structure and function."} {"id": "PMID:1270418", "title": "Bovine secretory component. Isolation, molecular size and shape, composition, and NH2-terminal amino acid sequence.", "content": "Bovine free secretory component was purified from whey by salt precipitation, gel filtration, DEAE-cellulose and phosphocellulose chromatography, and immunoadsorption. It was obtained in immunologically pure form and in 56% yield. The Stokes radius of pure free secretory component was found to be 4.3 nm by gel filtration, and an (see article) of 4.1 S was determined by the ultracentrifuge. The molecular weight was 79,000 by sodium dodecyl sulfate gel electrophoresis and by sedimentation dquilibrium in the ultracentrifuge, using a v of 0.73 determined by ultracentrifugation in D2O and H2O. A minimal axial ratio of approximately 5 was calculated. Amino acid analysis of bovine free secretory component showed remarkable similarity to that of human, dog, and rabbit but carbohydrate analysis showed significant differences. In contrast to the human, bovine free secretory compoennt has 2 methionine residues/mol. The NH2-terminal sequence was found to be Lys-Ser-Pro-Ile-PPHE-Gly-Pro-Glu-Glu-Val-Asp-Ser-Val. This sequence is identical with that the human and dog. However, the poor immunological cross-reactivity between the dog, human, and bovine proteins suggests that significant structural differences will be found in other regions of the molecule.", "contents": "Bovine secretory component. Isolation, molecular size and shape, composition, and NH2-terminal amino acid sequence. Bovine free secretory component was purified from whey by salt precipitation, gel filtration, DEAE-cellulose and phosphocellulose chromatography, and immunoadsorption. It was obtained in immunologically pure form and in 56% yield. The Stokes radius of pure free secretory component was found to be 4.3 nm by gel filtration, and an (see article) of 4.1 S was determined by the ultracentrifuge. The molecular weight was 79,000 by sodium dodecyl sulfate gel electrophoresis and by sedimentation dquilibrium in the ultracentrifuge, using a v of 0.73 determined by ultracentrifugation in D2O and H2O. A minimal axial ratio of approximately 5 was calculated. Amino acid analysis of bovine free secretory component showed remarkable similarity to that of human, dog, and rabbit but carbohydrate analysis showed significant differences. In contrast to the human, bovine free secretory compoennt has 2 methionine residues/mol. The NH2-terminal sequence was found to be Lys-Ser-Pro-Ile-PPHE-Gly-Pro-Glu-Glu-Val-Asp-Ser-Val. This sequence is identical with that the human and dog. However, the poor immunological cross-reactivity between the dog, human, and bovine proteins suggests that significant structural differences will be found in other regions of the molecule."} {"id": "PMID:1270419", "title": "Purification and characterization of a prokaryotic glycoprotein from the cell envelope of Halobacterium salinarium.", "content": "The glycoprotein which accounts for approximately 50% of the protein and all of the nonlipid carbohydrate of the cell envelope of Halobacterium salinarium (Mescher, M. F., Strominger, J. L., and Watson S. W. (1974) J. Bacteriol. 120, 945-954) has been purified and partially characterized. The glycoprotein has an apparent molecular weight of 200,000, is extremely acidic, and has a carbohydrate content of approximately 10 to 12%. The carbohydrate included neutral hexoses, amino sugar, and uronic acid. Information regarding the number, composition, and mode of attachment of the carbohydrate chains was obtained by isolation and examination of the glycopeptides derived from degradation of cell envelope protein with trypsin and pronase. Trypsin digestion resulted in two glycopeptides. One of these was large (approximately 55,000 daltons) and had most of the neutral hexose linked to it. The carbohydrate moieties consisted of di- and trisaccharides of glucosylgalactose and (uronic acid, glucose)-galactose attached via O-glycosidic linkages between galactose and threonine. The other tryptic glycopeptide had a relatively large heterosaccharide attached to it via an alkaline-stable linkage. The heterosaccharide contained 1 glucose, 8 to 9 galactose, 1 mannose, and 10 to 11 glucosamine residues, and approximately 6 residues of an unidentified amino augar. The alkaline stability of the linkage and the amino acid composition of glycopeptides resulting from Pronase digestion of the tryptic glycopeptide showed that the heterosaccharide was attached to an asparagine residue, presumably via an N-glycosylamine bond to the amide group. The intact glycoprotein has a single N-linked heterosaccharide, 22 to 24 O-linked disaccharides, and 12 to 14 O-linked trisaccharides per molecule. N- and O-glycosidic linkages are the most common carbohydrate-protein linkages in mammalian glycoproteins but, to our knowledge, this is the first report of either type of linkage in a prokaryotic cell envelope protein.", "contents": "Purification and characterization of a prokaryotic glycoprotein from the cell envelope of Halobacterium salinarium. The glycoprotein which accounts for approximately 50% of the protein and all of the nonlipid carbohydrate of the cell envelope of Halobacterium salinarium (Mescher, M. F., Strominger, J. L., and Watson S. W. (1974) J. Bacteriol. 120, 945-954) has been purified and partially characterized. The glycoprotein has an apparent molecular weight of 200,000, is extremely acidic, and has a carbohydrate content of approximately 10 to 12%. The carbohydrate included neutral hexoses, amino sugar, and uronic acid. Information regarding the number, composition, and mode of attachment of the carbohydrate chains was obtained by isolation and examination of the glycopeptides derived from degradation of cell envelope protein with trypsin and pronase. Trypsin digestion resulted in two glycopeptides. One of these was large (approximately 55,000 daltons) and had most of the neutral hexose linked to it. The carbohydrate moieties consisted of di- and trisaccharides of glucosylgalactose and (uronic acid, glucose)-galactose attached via O-glycosidic linkages between galactose and threonine. The other tryptic glycopeptide had a relatively large heterosaccharide attached to it via an alkaline-stable linkage. The heterosaccharide contained 1 glucose, 8 to 9 galactose, 1 mannose, and 10 to 11 glucosamine residues, and approximately 6 residues of an unidentified amino augar. The alkaline stability of the linkage and the amino acid composition of glycopeptides resulting from Pronase digestion of the tryptic glycopeptide showed that the heterosaccharide was attached to an asparagine residue, presumably via an N-glycosylamine bond to the amide group. The intact glycoprotein has a single N-linked heterosaccharide, 22 to 24 O-linked disaccharides, and 12 to 14 O-linked trisaccharides per molecule. N- and O-glycosidic linkages are the most common carbohydrate-protein linkages in mammalian glycoproteins but, to our knowledge, this is the first report of either type of linkage in a prokaryotic cell envelope protein."} {"id": "PMID:1270420", "title": "Analysis of ribonuclease-nucleotide interactions by quantitative affinity chromatography.", "content": "Quantitative affinity chromatography on uridine-5'-(Sepharose-4-aminophenylphosphoryl)-2'(3')-phosphate was developed for the study of binding of ribonuclease species to nucleotide ligands. Elution of the native species ribonuclease-A and -S on the afffinity matrix in 0.4 M ammonium acetate, pH 5.2, containing various amounts of the soluble competing ligand 2'-cytidine monophosphate, reveals an inverse response of elution volume to concentration of soluble ligand. This response conforms to behavior expected for the competing binding equilibria enzyme-soluble ligand and enzyme-insoluble ligand. A-NALYSIS OF ELUTION DATA ALLOWS CALCULATION OF KI and KIM, the dissociation constants, respectively, for the soluble and insoluble protein-ligand complexes. The values of these chromatographically derived constants are similar to values of dissocation constants determined in solution by kinetics of inhibition by 2'-cytidine monophosphate and uridine-5'-(j-aminophenylphosphoryl)-2'(3')-phosphate. Successful competitive elution experiments with [p-F-Phe8]semisynthetic ribonuclease-S' and individual elution trials for [4-F-His12]semisynthetic ribonuclease-S' indicate the utility of the quantitative affinity chromatographic technique for determination of ligand binding properties of ribonuclease derivatives, including inactive species. Nonbiospecific aspects of the interaction of ribonuclease with the affinity matrix in ammonium acetate buffers of concentrations 0.1 M and below were noted, delinating limits of conditions allowing the biospecificity needed for ligand-binding analyses by competitive elution. The dependence of ribonuclease competitive elution behavior on the amount of protein eluted also was examined and related to theoretical considerations in the quantitative application of affinity chromatography.", "contents": "Analysis of ribonuclease-nucleotide interactions by quantitative affinity chromatography. Quantitative affinity chromatography on uridine-5'-(Sepharose-4-aminophenylphosphoryl)-2'(3')-phosphate was developed for the study of binding of ribonuclease species to nucleotide ligands. Elution of the native species ribonuclease-A and -S on the afffinity matrix in 0.4 M ammonium acetate, pH 5.2, containing various amounts of the soluble competing ligand 2'-cytidine monophosphate, reveals an inverse response of elution volume to concentration of soluble ligand. This response conforms to behavior expected for the competing binding equilibria enzyme-soluble ligand and enzyme-insoluble ligand. A-NALYSIS OF ELUTION DATA ALLOWS CALCULATION OF KI and KIM, the dissociation constants, respectively, for the soluble and insoluble protein-ligand complexes. The values of these chromatographically derived constants are similar to values of dissocation constants determined in solution by kinetics of inhibition by 2'-cytidine monophosphate and uridine-5'-(j-aminophenylphosphoryl)-2'(3')-phosphate. Successful competitive elution experiments with [p-F-Phe8]semisynthetic ribonuclease-S' and individual elution trials for [4-F-His12]semisynthetic ribonuclease-S' indicate the utility of the quantitative affinity chromatographic technique for determination of ligand binding properties of ribonuclease derivatives, including inactive species. Nonbiospecific aspects of the interaction of ribonuclease with the affinity matrix in ammonium acetate buffers of concentrations 0.1 M and below were noted, delinating limits of conditions allowing the biospecificity needed for ligand-binding analyses by competitive elution. The dependence of ribonuclease competitive elution behavior on the amount of protein eluted also was examined and related to theoretical considerations in the quantitative application of affinity chromatography."} {"id": "PMID:1270421", "title": "Accumulation of analgo of phosphocreatine in muscle of chicks fed 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine).", "content": "Newly hatched chicks fed a commercial diet containing 1% cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) rapidly accumulate in breast muscle a derivative of cyclocreatine; within a few days concentrations up to 35 mumol of this derivative/g fresh weight of muscle are attained. The following evidence suggests that this derivative is N-phosphorylated cyclocreatine. (a) The derivative is adsorbed by Dowex 1 resin and eluted near phosphocreatine. (b) The derivative present in muscle is converted to free cyclocreatine either by homogenization of muscle in water at room temperature, conditions under which endogenous creatine kinase is active, or by heating a cold acidic muscle extract at 65 degrees for 45 min. (c) The isolated derivative reacts in vitro with the specific reagents crystalline creatine kinase and MgADP to give cyclocreatine. Essentially all of breast muscle cyclocreatine appears to be in the form of P-cyclocreatine, which persists in muscle long after cyclocreatine is removed from the diet. Long term conservation of P-cyclocreatine in muscle is aided by the fact that, unlike P-creatine, P-cyclocreatine is not continuously degraded to an inactive cyclic lactam. It is suggested that the maximal concentrations of P-cyclocreatine2- (and P-creatine2-) attained in sarcoplasm not only affect the phosphorylation potential of muscle cells, but also can account for more than half of the normal inorganic cation concentration of muscle sarcoplasm, and hence play an important role in muscle function. Other chick tissues active in accumulation of cyclocreatine are heart (up to 20 mumol/g fresh weight within 11 days on the diet) and brain (up to 10 mumol/g fresh weight after 30 days on the diet). Addition of 1% creatine to the diet of cyclocreatine-fed chicks does not prevent accumulation of cyclocreatine in muscle. Chicks fed cyclocreatine do not grow as rapidly as those on control diets, but they appear healthy, and mortality is very low when oxytetracycline is added to the drinking water. Cyclocreatine is also taken up by rat muscle, heart, and brain. A sensitive and specific assay for cyclocreatine has been developed. Cyclocreatine reacts with an aged aqueous solution of Na3[Fe(CN)8NH3] under alkaline conditions to give a blue product with a molar absorption coefficient (epsilon) of 4,400 M(-1) cm(\u00bf at 605 nm. The following compounds give an epsilon605 in this assay of less than 4 M%\u00bf cm(% N-phosphorylcyclocreatine, creatine, P-creatine, creatinine, 1-carboxymethyl-2-iminohexahydropyrimidine, guanidinoacetate, 3-guanidinopropionate, and arginine. Cyclocreatine does not interfere with the diacetyl-alpha-naphthol assay for creatine.", "contents": "Accumulation of analgo of phosphocreatine in muscle of chicks fed 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine). Newly hatched chicks fed a commercial diet containing 1% cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) rapidly accumulate in breast muscle a derivative of cyclocreatine; within a few days concentrations up to 35 mumol of this derivative/g fresh weight of muscle are attained. The following evidence suggests that this derivative is N-phosphorylated cyclocreatine. (a) The derivative is adsorbed by Dowex 1 resin and eluted near phosphocreatine. (b) The derivative present in muscle is converted to free cyclocreatine either by homogenization of muscle in water at room temperature, conditions under which endogenous creatine kinase is active, or by heating a cold acidic muscle extract at 65 degrees for 45 min. (c) The isolated derivative reacts in vitro with the specific reagents crystalline creatine kinase and MgADP to give cyclocreatine. Essentially all of breast muscle cyclocreatine appears to be in the form of P-cyclocreatine, which persists in muscle long after cyclocreatine is removed from the diet. Long term conservation of P-cyclocreatine in muscle is aided by the fact that, unlike P-creatine, P-cyclocreatine is not continuously degraded to an inactive cyclic lactam. It is suggested that the maximal concentrations of P-cyclocreatine2- (and P-creatine2-) attained in sarcoplasm not only affect the phosphorylation potential of muscle cells, but also can account for more than half of the normal inorganic cation concentration of muscle sarcoplasm, and hence play an important role in muscle function. Other chick tissues active in accumulation of cyclocreatine are heart (up to 20 mumol/g fresh weight within 11 days on the diet) and brain (up to 10 mumol/g fresh weight after 30 days on the diet). Addition of 1% creatine to the diet of cyclocreatine-fed chicks does not prevent accumulation of cyclocreatine in muscle. Chicks fed cyclocreatine do not grow as rapidly as those on control diets, but they appear healthy, and mortality is very low when oxytetracycline is added to the drinking water. Cyclocreatine is also taken up by rat muscle, heart, and brain. A sensitive and specific assay for cyclocreatine has been developed. Cyclocreatine reacts with an aged aqueous solution of Na3[Fe(CN)8NH3] under alkaline conditions to give a blue product with a molar absorption coefficient (epsilon) of 4,400 M(-1) cm(\u00bf at 605 nm. The following compounds give an epsilon605 in this assay of less than 4 M%\u00bf cm(% N-phosphorylcyclocreatine, creatine, P-creatine, creatinine, 1-carboxymethyl-2-iminohexahydropyrimidine, guanidinoacetate, 3-guanidinopropionate, and arginine. Cyclocreatine does not interfere with the diacetyl-alpha-naphthol assay for creatine."} {"id": "PMID:1270422", "title": "Fragments formed by the side chain cleavage of a 20-aryl analog of 20alpha-hydroxycholesterol by adrenal mitochondria.", "content": "An analog of 20alpha-hydroxycholesterol, (20R)-20-phenyl-5-pregnene-3beta,20-diol, which is completely substituted at C-22 was prepared with radioisotopes at various positions. The analog labeled with 3H at C-M and 14C at C-4 and C-IU was converted into radioactive pregnenolone by an enzyme preparation derived from adrenal mitochondria. Cleavage of the phenyl analog labeled with 3H in the aromatic ring by the same enzyme preparation led to the formation of [3H]phenol. Using the substrate doubly labeled with 14C at C-4 and 3H in the aromatic ring, it appeared that the products of the reactions, pregnenolone and phenol, were formed in equal amounts. During incubation of the side chain labeled substrate, another labeled fragment was formed. It was identified as acetophenone, a product resulting from cleavage of the C17,20 bond. The steroidal fragment corresponding to this C8 ketone was traced using nuclear label analog. From its nonpolar chromatographic properties it appears to be a C-17-deoxy-C19 steroid.", "contents": "Fragments formed by the side chain cleavage of a 20-aryl analog of 20alpha-hydroxycholesterol by adrenal mitochondria. An analog of 20alpha-hydroxycholesterol, (20R)-20-phenyl-5-pregnene-3beta,20-diol, which is completely substituted at C-22 was prepared with radioisotopes at various positions. The analog labeled with 3H at C-M and 14C at C-4 and C-IU was converted into radioactive pregnenolone by an enzyme preparation derived from adrenal mitochondria. Cleavage of the phenyl analog labeled with 3H in the aromatic ring by the same enzyme preparation led to the formation of [3H]phenol. Using the substrate doubly labeled with 14C at C-4 and 3H in the aromatic ring, it appeared that the products of the reactions, pregnenolone and phenol, were formed in equal amounts. During incubation of the side chain labeled substrate, another labeled fragment was formed. It was identified as acetophenone, a product resulting from cleavage of the C17,20 bond. The steroidal fragment corresponding to this C8 ketone was traced using nuclear label analog. From its nonpolar chromatographic properties it appears to be a C-17-deoxy-C19 steroid."} {"id": "PMID:1270423", "title": "Transmembrane asymmetry of vesicle lipids.", "content": "The role of fatty acyl chain unsaturation in promoting asymmetry in phospholipid vesicle bilayers was investigated in mixed lipid systems with differing acyl chains and a constant phosphatidylcholine headgroup. Ratios of outside to inside components were determined by nuclear magnetic resonance spectroscopy of 13C-enriched egg phosphatidylcholine. An asymmetry or disproportionation ratio is defined and used to express quantitatively how a mixture of two lipids distributes in the outer and inner vesicle surfaces. In mixed systems with 13C-enriched egg phosphatidylcholine as one component, increasing fatty acyl unsaturation in the other component results in an increasing preference of the unsaturated chains for the outer surface.", "contents": "Transmembrane asymmetry of vesicle lipids. The role of fatty acyl chain unsaturation in promoting asymmetry in phospholipid vesicle bilayers was investigated in mixed lipid systems with differing acyl chains and a constant phosphatidylcholine headgroup. Ratios of outside to inside components were determined by nuclear magnetic resonance spectroscopy of 13C-enriched egg phosphatidylcholine. An asymmetry or disproportionation ratio is defined and used to express quantitatively how a mixture of two lipids distributes in the outer and inner vesicle surfaces. In mixed systems with 13C-enriched egg phosphatidylcholine as one component, increasing fatty acyl unsaturation in the other component results in an increasing preference of the unsaturated chains for the outer surface."} {"id": "PMID:1270424", "title": "Self-association of cytochrome b5 in aqueous solution. Gel filtration and ultracentirfugational studies.", "content": "The aggregation state of detergent-extracted cytochrome b5 was examined by gel filtration and sedimentation equilibrium ultracentrifugation. Both techniques indicated the presence of a mixture of monomer and octomer. The proportion of monomer was decreased as the buffer salt concentration was raised and was approximately 1 muM in 10 mM Tris acetate/0.1 mM EDTA. The monomeric cytochrome b5 was isolated by gel filtration and showed a decreased tendency to aggregate in dilute buffer, although its other physical properties were identical to those of the original cytochrome b5. The monomer was found to have a Stokes radius of approximately 26 A, as determined by classical gel filtration and by an equilibrium saturation method where the sample was monitored in the gel by measuring the absorbance of the gel column directly in a dual wavelength spectrophotometer. The gel filtration and ultracentrifugation data together with the studied on the monomeric cytochrome b5 suggest the octomer is not a rapid equilibrium with monomer and this observation should be taken into account in lipid binding experiments with cytochrome b5.", "contents": "Self-association of cytochrome b5 in aqueous solution. Gel filtration and ultracentirfugational studies. The aggregation state of detergent-extracted cytochrome b5 was examined by gel filtration and sedimentation equilibrium ultracentrifugation. Both techniques indicated the presence of a mixture of monomer and octomer. The proportion of monomer was decreased as the buffer salt concentration was raised and was approximately 1 muM in 10 mM Tris acetate/0.1 mM EDTA. The monomeric cytochrome b5 was isolated by gel filtration and showed a decreased tendency to aggregate in dilute buffer, although its other physical properties were identical to those of the original cytochrome b5. The monomer was found to have a Stokes radius of approximately 26 A, as determined by classical gel filtration and by an equilibrium saturation method where the sample was monitored in the gel by measuring the absorbance of the gel column directly in a dual wavelength spectrophotometer. The gel filtration and ultracentrifugation data together with the studied on the monomeric cytochrome b5 suggest the octomer is not a rapid equilibrium with monomer and this observation should be taken into account in lipid binding experiments with cytochrome b5."} {"id": "PMID:1270425", "title": "Purification and physical characterization of nucleic acid helix-unwinding proteins from calf thymus.", "content": "We have devised a general protein fractionation procedure which selects for eukaryotic DNA-binding proteins, some of which resemble DNA-unwinding proteins from prokaryotes. Proteins were selected which (a) pass through a native DNA-cellulose column, (b) bind to a denatured DNA-cellulose column, and (c) remain bound to the latter column during a rinse with a dilute solution of the sodium salt of the polyanion dextran sulfate. When this fractionation was applied to the soluble proteins fo calf thymus, three major protein species were recovered. The predominant one has an apparent molecular weight of about 24,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is isoelectric near neutrality, and elutes as a monomer from denatured DNA-cellulose at moderate NaCl concentrations. This protein, designated calf-unwinding protein 1 (UP1), has been purified to homogeneity. However, isoelectric focusing reveals four or five subspecies (apparently separated by single-charge differences) which differ appreciably in their affinities for DNA. Two other major proteins are obtained which have apparent molecular weights in sodium dodecyl sulfate of 33,000: the first, which elutes with low salt from DNA-cellulose as a homogeneous preparation, appears to be a basic protein (although it is clearly not a histone); the other, which elutes from DNA-cellulose as the major component of a \"high salt eluting fraction,\" is an acidic protein which co-purifies with less prominent species of higher molecular weights. Proteins similar to each of these three major calf thymus proteins have been observed by us and others in tissue culture cells of mouse, hamster, monkey, and humans, suggesting their wide occurrence among eukaryotes.", "contents": "Purification and physical characterization of nucleic acid helix-unwinding proteins from calf thymus. We have devised a general protein fractionation procedure which selects for eukaryotic DNA-binding proteins, some of which resemble DNA-unwinding proteins from prokaryotes. Proteins were selected which (a) pass through a native DNA-cellulose column, (b) bind to a denatured DNA-cellulose column, and (c) remain bound to the latter column during a rinse with a dilute solution of the sodium salt of the polyanion dextran sulfate. When this fractionation was applied to the soluble proteins fo calf thymus, three major protein species were recovered. The predominant one has an apparent molecular weight of about 24,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, is isoelectric near neutrality, and elutes as a monomer from denatured DNA-cellulose at moderate NaCl concentrations. This protein, designated calf-unwinding protein 1 (UP1), has been purified to homogeneity. However, isoelectric focusing reveals four or five subspecies (apparently separated by single-charge differences) which differ appreciably in their affinities for DNA. Two other major proteins are obtained which have apparent molecular weights in sodium dodecyl sulfate of 33,000: the first, which elutes with low salt from DNA-cellulose as a homogeneous preparation, appears to be a basic protein (although it is clearly not a histone); the other, which elutes from DNA-cellulose as the major component of a \"high salt eluting fraction,\" is an acidic protein which co-purifies with less prominent species of higher molecular weights. Proteins similar to each of these three major calf thymus proteins have been observed by us and others in tissue culture cells of mouse, hamster, monkey, and humans, suggesting their wide occurrence among eukaryotes."} {"id": "PMID:1270426", "title": "Nucleic acid helix-coil transitions mediated by helix-unwinding proteins from calf thymus.", "content": "We have studied nucleic acid double helix destabilization mediated by purified calf helix-unwinding proteins, measuring ultraviolet hyperchromicity to detect helix melting. Both calf unwinding protein 1 (UP1) and a high salt eluting protein fraction are found to depress strongly the helix melting temperature (Tm) of the synthetic alternating copolymers poly[d(AT)] and poly[r(AU)], indicating that both DNA and RNA are recognized by these proteins. UP1 also destabilizes natural, GC-containing DNA helices, but to a smaller extent than observed with the above polymers. A simple model is presented to aid in the qualitative interpretation of the data, outlining the expected effect on the helix-coil transition of a protein ligand with differential affinity for the helix or coil form of nucleic acid. The observed helix-destabilizing effect of UP1 is dependent on the protein to nucleic acid ratio in an expected manner. Competition studies demonstrate a low, but appreciable affinity of UP1 for native DNA, opening the possibility that protein-mediated denaturation might be initiated by protein binding to the double helix. \"Hairpin\" helical regions of denatured DNA are strongly destabilized by UP1. Despite the fact that removal of these hairpin helices might greatly facilitate DNA renaturation, we failed to observe renaturation from the UP1-DNA complex after a switch to helix-stabilizing conditions. Thus, UP1 shows an important difference from its presumed prokaryotic analogue, T4 gene 32-protein. Possible in vivo functions of the calf proteins are discussed in light of these observations.", "contents": "Nucleic acid helix-coil transitions mediated by helix-unwinding proteins from calf thymus. We have studied nucleic acid double helix destabilization mediated by purified calf helix-unwinding proteins, measuring ultraviolet hyperchromicity to detect helix melting. Both calf unwinding protein 1 (UP1) and a high salt eluting protein fraction are found to depress strongly the helix melting temperature (Tm) of the synthetic alternating copolymers poly[d(AT)] and poly[r(AU)], indicating that both DNA and RNA are recognized by these proteins. UP1 also destabilizes natural, GC-containing DNA helices, but to a smaller extent than observed with the above polymers. A simple model is presented to aid in the qualitative interpretation of the data, outlining the expected effect on the helix-coil transition of a protein ligand with differential affinity for the helix or coil form of nucleic acid. The observed helix-destabilizing effect of UP1 is dependent on the protein to nucleic acid ratio in an expected manner. Competition studies demonstrate a low, but appreciable affinity of UP1 for native DNA, opening the possibility that protein-mediated denaturation might be initiated by protein binding to the double helix. \"Hairpin\" helical regions of denatured DNA are strongly destabilized by UP1. Despite the fact that removal of these hairpin helices might greatly facilitate DNA renaturation, we failed to observe renaturation from the UP1-DNA complex after a switch to helix-stabilizing conditions. Thus, UP1 shows an important difference from its presumed prokaryotic analogue, T4 gene 32-protein. Possible in vivo functions of the calf proteins are discussed in light of these observations."} {"id": "PMID:1270427", "title": "Single-stranded DNA structure and DNA polymerase activity in the presence of nucleic acid helix-unwinding proteins from calf thymus.", "content": "In the preceding articles we have described the isolation and some of the properties of two calf thymus proteins which bind selectively to single-stranded DNA and which appear analogous to previously isolated prokaryotic DNA-unwinding proteins. In the present work we demonstrate two further points of analogy. First, both the calf UP1 and the high salt eluting proteins form protein-rich complexes with single-stranded DNA, and hold this DNA in a rigid, extended conformation. Second, these proteins stimulate the calf thymus DNA polymerase-alpha; phage T4 gene 32-protein does not. The stimulation of a homologous DNA polymerase is characteristic of several prokaryotic DNA-unwinding proteins and is assumed to reflect their in vivo role in DNA synthesis.", "contents": "Single-stranded DNA structure and DNA polymerase activity in the presence of nucleic acid helix-unwinding proteins from calf thymus. In the preceding articles we have described the isolation and some of the properties of two calf thymus proteins which bind selectively to single-stranded DNA and which appear analogous to previously isolated prokaryotic DNA-unwinding proteins. In the present work we demonstrate two further points of analogy. First, both the calf UP1 and the high salt eluting proteins form protein-rich complexes with single-stranded DNA, and hold this DNA in a rigid, extended conformation. Second, these proteins stimulate the calf thymus DNA polymerase-alpha; phage T4 gene 32-protein does not. The stimulation of a homologous DNA polymerase is characteristic of several prokaryotic DNA-unwinding proteins and is assumed to reflect their in vivo role in DNA synthesis."} {"id": "PMID:1270428", "title": "Phosphorylation of axonemal proteins in Chlamydomonas reinhardtii.", "content": "In order to determine whether microtubular proteins of flagellar axonemes were phosphorylated, cells of Chlamydomonas reinhardtii were grown in medium containing [32P]orthophosphate for several generations. Only one (alpha subunit) of the two tubulin polypeptides separated by Na dodecyl-SO4-polyacrylamide gel electrophoresis appeared labeled, as detected by autoradiography of the dried gel. 3H- and 32P-labeled alpha tubulin subunit purified by preparative Na dodecyl-SO4-polyacrylamide gel electrophoresis and Na dodecyl-SO4-hydroxyapatite chromatography contained about 0.2 mol of phosphate per mol of polypeptide. Upon partial acid hydrolysis, radioactivity could be accounted for as serine and threonine phosphate. By altering the conditions of the Na dodecyl-SO4-polyacrylamide gel electrophoresis is was possible to resolve the purified alpha-tubulin subunit into five or more components: a major band comprising approximately 65% of the total mass, not phosphorylated, and four or more minor bands comprising together 35% of the mass. Among the minor components at least two were phosphorylated.", "contents": "Phosphorylation of axonemal proteins in Chlamydomonas reinhardtii. In order to determine whether microtubular proteins of flagellar axonemes were phosphorylated, cells of Chlamydomonas reinhardtii were grown in medium containing [32P]orthophosphate for several generations. Only one (alpha subunit) of the two tubulin polypeptides separated by Na dodecyl-SO4-polyacrylamide gel electrophoresis appeared labeled, as detected by autoradiography of the dried gel. 3H- and 32P-labeled alpha tubulin subunit purified by preparative Na dodecyl-SO4-polyacrylamide gel electrophoresis and Na dodecyl-SO4-hydroxyapatite chromatography contained about 0.2 mol of phosphate per mol of polypeptide. Upon partial acid hydrolysis, radioactivity could be accounted for as serine and threonine phosphate. By altering the conditions of the Na dodecyl-SO4-polyacrylamide gel electrophoresis is was possible to resolve the purified alpha-tubulin subunit into five or more components: a major band comprising approximately 65% of the total mass, not phosphorylated, and four or more minor bands comprising together 35% of the mass. Among the minor components at least two were phosphorylated."} {"id": "PMID:1270430", "title": "Exchange and stability of HeLa ribosomal proteins in vivo.", "content": "The relative stabilities of individual HeLa ribosomal proteins and their capacity for exchange between ribosome-bound and -free states in the cytoplasm were examined. Most ribosomal proteins on cytoplasmic ribosomes were found to have uniform, high stability as measured by comparing the short term (12-hour) to steady state (3-day) labeling ratios determined for each ribosomal protein. This would be expected if the proteins in ribosomes either were all stable or were all degraded as a unit. The data do not rule out the possibility that individual proteins have different stabilities prior to their assembly into ribosomes. Four proteins labeled atypically. One large subunit protein (L5) had a lower than average ratio. We interpret this low ratio as being due to a large free pool of this protein. Three proteins (L10, L28, S2) had higher than average ratios, interpreted as being due to reduced protein stability. Two of these proteins (L10, L28) with high ratios were also found to exchange in vivo. The exchangeable proteins may be subject to increased degradation during the time that they spend in the exchangeable free pool. The third protein (S2) with an atypically high ratio is thought to be degraded or altered while on the ribosome, or slowly lost as ribosomes age, because exchange of this protein was not detected. These interpretations and some alternate interpretations are explained. The exchange of three large subunit proteins (L10, L19, L28) was detected by labeling of protein after ribosome synthesis had been inhibited with actinomycin D. Autoradiography of two-dimensional polyacrylamide gels showed labeling of these spots.", "contents": "Exchange and stability of HeLa ribosomal proteins in vivo. The relative stabilities of individual HeLa ribosomal proteins and their capacity for exchange between ribosome-bound and -free states in the cytoplasm were examined. Most ribosomal proteins on cytoplasmic ribosomes were found to have uniform, high stability as measured by comparing the short term (12-hour) to steady state (3-day) labeling ratios determined for each ribosomal protein. This would be expected if the proteins in ribosomes either were all stable or were all degraded as a unit. The data do not rule out the possibility that individual proteins have different stabilities prior to their assembly into ribosomes. Four proteins labeled atypically. One large subunit protein (L5) had a lower than average ratio. We interpret this low ratio as being due to a large free pool of this protein. Three proteins (L10, L28, S2) had higher than average ratios, interpreted as being due to reduced protein stability. Two of these proteins (L10, L28) with high ratios were also found to exchange in vivo. The exchangeable proteins may be subject to increased degradation during the time that they spend in the exchangeable free pool. The third protein (S2) with an atypically high ratio is thought to be degraded or altered while on the ribosome, or slowly lost as ribosomes age, because exchange of this protein was not detected. These interpretations and some alternate interpretations are explained. The exchange of three large subunit proteins (L10, L19, L28) was detected by labeling of protein after ribosome synthesis had been inhibited with actinomycin D. Autoradiography of two-dimensional polyacrylamide gels showed labeling of these spots."} {"id": "PMID:1270431", "title": "Relative stoichiometry in ribosomal proteins in HeLa cell nucleoli.", "content": "Total protein was released from isolated HeLa cell nucleoli by guanidine hydrochloride, purified by cesium chloride density gradient centrifugation, and analyzed by two-dimensional polyacrylamide gel electrophoresis. Conditions of electrophoresis restricted attention to proteins that are positively charged at pH 8.6. Most of the major nucleolar protein spots co-electrophoresed with ribosomal proteins; the majority of ribosomal proteins from both the large and small ribosomal subunits were represented. Several proteins found in association with polysomes but not on ribosomal subunits and several proteins unique to the nucleolus were also identified in these nucleolar protein patterns. In order to determine whether the ribosomal proteins found in the nucleolus represented sizable pools of ribosomal proteins, or merely ribosomal proteins contained in the preribosomal particles, [35S]methionine-labeled nucleoli were mixed with [3H]methionine-labeled polysomes. From analysis of isotopic ratios in individual protein spots it was possible to determine the stoidchiometry of individual ribosomal proteins in the nucleolus relative to their complement on cytoplasmic ribosomes. All but a few proteins exhibited relative nucleolar stoichiometry values of approximately one, indicating that there are not significant pools of most ribosomal proteins in isolated nucleoli.", "contents": "Relative stoichiometry in ribosomal proteins in HeLa cell nucleoli. Total protein was released from isolated HeLa cell nucleoli by guanidine hydrochloride, purified by cesium chloride density gradient centrifugation, and analyzed by two-dimensional polyacrylamide gel electrophoresis. Conditions of electrophoresis restricted attention to proteins that are positively charged at pH 8.6. Most of the major nucleolar protein spots co-electrophoresed with ribosomal proteins; the majority of ribosomal proteins from both the large and small ribosomal subunits were represented. Several proteins found in association with polysomes but not on ribosomal subunits and several proteins unique to the nucleolus were also identified in these nucleolar protein patterns. In order to determine whether the ribosomal proteins found in the nucleolus represented sizable pools of ribosomal proteins, or merely ribosomal proteins contained in the preribosomal particles, [35S]methionine-labeled nucleoli were mixed with [3H]methionine-labeled polysomes. From analysis of isotopic ratios in individual protein spots it was possible to determine the stoidchiometry of individual ribosomal proteins in the nucleolus relative to their complement on cytoplasmic ribosomes. All but a few proteins exhibited relative nucleolar stoichiometry values of approximately one, indicating that there are not significant pools of most ribosomal proteins in isolated nucleoli."} {"id": "PMID:1270432", "title": "Role of changes in protein degradation in the growth of regenerating livers.", "content": "The significance of changes in rates of synthesis, export, and degradation of proteins during liver regeneration was assessed. (a) Proteins were pulse labeled by the intravenous injection of radioactive leucine and, 5 min later, pactamycin (an inhibitor of the initiation of protein synthesis). One-half of the protein radioactivity was lost from the normal liver within 3 hours. From the radioactivity of the plasma proteins at that time and a study of the disappearance of these proteins from the circulation, it was calculated that 28% of the newly synthesized proteins were exported. Serum albumin accounted for a third of the exported proteins. Thirty-six hours after partial hepatectomy the proportion of albumin to total protein synthesis remained constant, while that of the other plasma proteins increased by 50%. The fraction of the newly synthesized proteins retained by the liver after 3 hours decreased by 20%. (b) During the first 36 hours of liver regeneration the average rates of protein degradation slowed down to one-half the normal values. This was determined either by the loss of radioactivity from total protein (or the guanidino-C of protein-bound arginine) in livers labeled with [14C]bicarbonate, or calculated as the balance between protein synthesis and net protein gain. (c) From these results, and those of our previous study of the protein synthetic machinery of normal and regenerating livers (Scornik, O.A. (1974)J. Biol. Chem. 249, 3876-3883), we conclude that changes in the rate of protein degradation are the single most important factor determining the increase in protein content during liver compensatory growth.", "contents": "Role of changes in protein degradation in the growth of regenerating livers. The significance of changes in rates of synthesis, export, and degradation of proteins during liver regeneration was assessed. (a) Proteins were pulse labeled by the intravenous injection of radioactive leucine and, 5 min later, pactamycin (an inhibitor of the initiation of protein synthesis). One-half of the protein radioactivity was lost from the normal liver within 3 hours. From the radioactivity of the plasma proteins at that time and a study of the disappearance of these proteins from the circulation, it was calculated that 28% of the newly synthesized proteins were exported. Serum albumin accounted for a third of the exported proteins. Thirty-six hours after partial hepatectomy the proportion of albumin to total protein synthesis remained constant, while that of the other plasma proteins increased by 50%. The fraction of the newly synthesized proteins retained by the liver after 3 hours decreased by 20%. (b) During the first 36 hours of liver regeneration the average rates of protein degradation slowed down to one-half the normal values. This was determined either by the loss of radioactivity from total protein (or the guanidino-C of protein-bound arginine) in livers labeled with [14C]bicarbonate, or calculated as the balance between protein synthesis and net protein gain. (c) From these results, and those of our previous study of the protein synthetic machinery of normal and regenerating livers (Scornik, O.A. (1974)J. Biol. Chem. 249, 3876-3883), we conclude that changes in the rate of protein degradation are the single most important factor determining the increase in protein content during liver compensatory growth."} {"id": "PMID:1270433", "title": "Interaction of anions and divalent metal ions with phosphoenolpyruvate carboxykinase.", "content": "The catalytic activity of phosphoenolpyruvate carboxykinase in rat liver cytosol is stimulated by incubating with Fe2+, Mn2+, Co2+, and Cd2+. When purified, the enzyme no longer responds to Fe2+, Co2+, or Cd2+ but retains a response to Mn2+. Low concentrations of SO4(2-) in the incubation medium with enzyme and divalent transition metal allow stimulation by Fe2+ and Co2+ and enhance the response to Mn2+. Under identical conditions, orthophosphate with Fe2+ is a potent inhibitor of the enzyme (half-maximal inhibition at 50 muM). A thiol is required in the incubation medium for the effects of Fe2+ plus sulfate or orthophosphate to be expressed. The magnitude of these effects depends on the thiol concentration. Dithiothreitol is more effective than GSH and activation by sulfate plus Fe2+ appears to require the reduced form of dithiothreitol. Sulfate ion is not considered to be the physiological Fe2+-activator of P-enolpyruvate carboxykinase in rat liver cytosol, as this function is fulfilled by a newly discovered liver protein. Knowledge concerning the interaction of Fe2+ and sulfate with the enzyme may be useful in examining their interaction between the enzyme, ferrous ion, and this activator protein.", "contents": "Interaction of anions and divalent metal ions with phosphoenolpyruvate carboxykinase. The catalytic activity of phosphoenolpyruvate carboxykinase in rat liver cytosol is stimulated by incubating with Fe2+, Mn2+, Co2+, and Cd2+. When purified, the enzyme no longer responds to Fe2+, Co2+, or Cd2+ but retains a response to Mn2+. Low concentrations of SO4(2-) in the incubation medium with enzyme and divalent transition metal allow stimulation by Fe2+ and Co2+ and enhance the response to Mn2+. Under identical conditions, orthophosphate with Fe2+ is a potent inhibitor of the enzyme (half-maximal inhibition at 50 muM). A thiol is required in the incubation medium for the effects of Fe2+ plus sulfate or orthophosphate to be expressed. The magnitude of these effects depends on the thiol concentration. Dithiothreitol is more effective than GSH and activation by sulfate plus Fe2+ appears to require the reduced form of dithiothreitol. Sulfate ion is not considered to be the physiological Fe2+-activator of P-enolpyruvate carboxykinase in rat liver cytosol, as this function is fulfilled by a newly discovered liver protein. Knowledge concerning the interaction of Fe2+ and sulfate with the enzyme may be useful in examining their interaction between the enzyme, ferrous ion, and this activator protein."} {"id": "PMID:1270434", "title": "A protein factor required for activation of phosphoenolpyruvate carboxykinase by ferrous ions.", "content": "When rat liver cytosolic P-enolpyruvate carboxykinase is purified, its activity is no longer enhanced by incubation with 30 muM Fe2+. Ferrous ion stimulation of the purified enzyme is restored by the addition of rat liver cytosol. The agent responsible is a cytosolic protein, named P-enolpyruvate carboxykinase ferroactivator, that was readily separated from the enzyme during purification of the latter. A quantitative assay for P-enolpyruvate carboxykinase ferroactivator is described. Subcellular fractionation of livers from fasted rats shows that 98% of the combined mitochondrial and cytosolic P-enolpyruvate carboxykinase ferroactivator activity resides in the cytosol. Fasting does not produce significant change in this cytosolic activity when compared to that of fed animals. Examination of various tissue homogenates shows that the ferroactivator is found in liver, kidney, erythrocytes, adipose tissue, and brain. No activity was detected in blood serum or skeletal muscle. The ability to enhance the activity of purified rat liver cytosolic P-enolpyruvate carboxykinase in the presence of Fe2+ is not species specific. P-enolpyruvate carboxykinase ferroactivator may have an important function in regulating enzyme activity in vivo.", "contents": "A protein factor required for activation of phosphoenolpyruvate carboxykinase by ferrous ions. When rat liver cytosolic P-enolpyruvate carboxykinase is purified, its activity is no longer enhanced by incubation with 30 muM Fe2+. Ferrous ion stimulation of the purified enzyme is restored by the addition of rat liver cytosol. The agent responsible is a cytosolic protein, named P-enolpyruvate carboxykinase ferroactivator, that was readily separated from the enzyme during purification of the latter. A quantitative assay for P-enolpyruvate carboxykinase ferroactivator is described. Subcellular fractionation of livers from fasted rats shows that 98% of the combined mitochondrial and cytosolic P-enolpyruvate carboxykinase ferroactivator activity resides in the cytosol. Fasting does not produce significant change in this cytosolic activity when compared to that of fed animals. Examination of various tissue homogenates shows that the ferroactivator is found in liver, kidney, erythrocytes, adipose tissue, and brain. No activity was detected in blood serum or skeletal muscle. The ability to enhance the activity of purified rat liver cytosolic P-enolpyruvate carboxykinase in the presence of Fe2+ is not species specific. P-enolpyruvate carboxykinase ferroactivator may have an important function in regulating enzyme activity in vivo."} {"id": "PMID:1270435", "title": "Lipophosphonoglycan of the plasma membrane of A canthamoeba castellanii. Inositol and phytosphingosine content and general structural features.", "content": "Lipophosphonoglycan, a major component of the plasma membrane of Acanthamoeba castellanii, has now been shown to contain 8% inositol and 13% C25- and C24-phytosphingosines in addition to the previously identified content of neutral sugars (26%), amino sugars (3%), aminophosphonates (10%), acidhydrolyzable phosphate (3%), and long chain fatty acids (14%). The fatty acids and phytosphingosines are in ceramide groups. Lipophosphonoglycan can be separated by dodecyl sulfate-polyacrylamide electrophoresis into two major components that are similar in composition except for different oligosaccharide groups. A tentative structural model incorporating these features is proposed in which each of the two components of lipophosphonoglycan is conceived as an oligomeric inositol-containing glycosphingolipid.", "contents": "Lipophosphonoglycan of the plasma membrane of A canthamoeba castellanii. Inositol and phytosphingosine content and general structural features. Lipophosphonoglycan, a major component of the plasma membrane of Acanthamoeba castellanii, has now been shown to contain 8% inositol and 13% C25- and C24-phytosphingosines in addition to the previously identified content of neutral sugars (26%), amino sugars (3%), aminophosphonates (10%), acidhydrolyzable phosphate (3%), and long chain fatty acids (14%). The fatty acids and phytosphingosines are in ceramide groups. Lipophosphonoglycan can be separated by dodecyl sulfate-polyacrylamide electrophoresis into two major components that are similar in composition except for different oligosaccharide groups. A tentative structural model incorporating these features is proposed in which each of the two components of lipophosphonoglycan is conceived as an oligomeric inositol-containing glycosphingolipid."} {"id": "PMID:1270436", "title": "Induction of amino acid transport in primary cultures of adult rat liver parenchymal cells by insulin.", "content": "Amino acid transport was studied in primary cultures of parenchymal cells isolated from adult rat liver by a collagenase perfusion technique and maintained as a monolayer in a serum-free culture medium. Amino acid transport was assayed by measuring the uptake of the nonmetabolizable amino acid, alpha-aminoisobutyric acid. Rat liver parenchymal cells transported alpha-aminoisobutyric acid by an energy-dependent Na+-requiring system which displayed Michaelis-Menten kinetics. Addition of insulin to cultured rat liver parenchymal cells resulted in an increased influx of alpha-aminoisobutyric acid which was reflected in a higher initial rate of alpha-aminoisobutyric acid transport as well as an increased accumulation of alpha-aminoisobutyric acid at later time points. Cycloheximide effectively blocked the increase while results with actinomycin D were equivocal. Insulin at concentrations as low as 50 pM was effective in stimulating alpha-aminoisobutyric acid transport while the maximal response was observed at 80 nM.", "contents": "Induction of amino acid transport in primary cultures of adult rat liver parenchymal cells by insulin. Amino acid transport was studied in primary cultures of parenchymal cells isolated from adult rat liver by a collagenase perfusion technique and maintained as a monolayer in a serum-free culture medium. Amino acid transport was assayed by measuring the uptake of the nonmetabolizable amino acid, alpha-aminoisobutyric acid. Rat liver parenchymal cells transported alpha-aminoisobutyric acid by an energy-dependent Na+-requiring system which displayed Michaelis-Menten kinetics. Addition of insulin to cultured rat liver parenchymal cells resulted in an increased influx of alpha-aminoisobutyric acid which was reflected in a higher initial rate of alpha-aminoisobutyric acid transport as well as an increased accumulation of alpha-aminoisobutyric acid at later time points. Cycloheximide effectively blocked the increase while results with actinomycin D were equivocal. Insulin at concentrations as low as 50 pM was effective in stimulating alpha-aminoisobutyric acid transport while the maximal response was observed at 80 nM."} {"id": "PMID:1270437", "title": "A new vitamin K-dependent protein. A phospholipid-binding zymogen of a serine esterase.", "content": "Conclusive evidence is presented that a recently purified (Stenflo, J. (1976) J. Biol. Chem. 251, 355-363) vitamin K-dependent protein (arbitrarily referred to as Protein C) which is not related to prothrombin, Factors IX or X is also unrelated to Factor VII. It therefore appears to be a new, previously unrecognized vitamin K-dependent protein. In contrast to prothrombin, which binds to negatively charged phospholipid only in the presence of Ca2+ ions, Protein C, like the other vitamin K-dependent proteins, is a precursor of a serine esterase, presumably a protease, but it does not seem to be necessary for blood coagulation. Although the lipid-binding properties of Protein C may suggest that it is associated with membrane structures, its biological function remains unknown.", "contents": "A new vitamin K-dependent protein. A phospholipid-binding zymogen of a serine esterase. Conclusive evidence is presented that a recently purified (Stenflo, J. (1976) J. Biol. Chem. 251, 355-363) vitamin K-dependent protein (arbitrarily referred to as Protein C) which is not related to prothrombin, Factors IX or X is also unrelated to Factor VII. It therefore appears to be a new, previously unrecognized vitamin K-dependent protein. In contrast to prothrombin, which binds to negatively charged phospholipid only in the presence of Ca2+ ions, Protein C, like the other vitamin K-dependent proteins, is a precursor of a serine esterase, presumably a protease, but it does not seem to be necessary for blood coagulation. Although the lipid-binding properties of Protein C may suggest that it is associated with membrane structures, its biological function remains unknown."} {"id": "PMID:1270438", "title": "In vitro translation and estradiol-17beta induction of Xenopus laevis vitellogenin messenger RNA.", "content": "Administration of estradiol-17beta to male Xenopus laevis induces synthesis and secretion by the liver of the egg yolk precursor protein vitellogenin. RNA extracted from livers of estradiol-17beta-treated Xenopus laevis directs the synthesis of the entire 200,000-dalton vitellogenin monomer in a cell-free protein synthesizing system derived from rabbit reticulocytes. Vitellogenin synthesized in vitro was isolated and quantitated by indirect immunoprecipitation and identified by comparison to authentic [14C]vitellogenin. The in vitro product and [14C]vitellogenin co-migrate on electrophoresis in sodium dodecyl sulfate-polyacrylamide gels and they exhibit identical immunoprecipitation curves. Xenopus laevis vitellogenin messenger RNA has a sedimentation coefficient of approximately 30 S in sucrose density gradients. It can be purified approximately 60-fold from cell RNA by poly(U)-Sepharose chromatography and therefore appears to contain a polyadenylate sequence. Vitellogenin mRNA and vitellogenin synthesis in vivo could not be detected in unstimulated male Xenopus laevis. The relative rate of vitellogenin synthesis and the level of vitellogenin mRNA were determined at various times following the administration of estradiol-17beta. Vitellogenin synthesis is maximal 12 days after estradiol-17beta administration when it comprises approximately 70% of cell protein synthesis. The level of vitellogenin mRNA and the intracellular rate of vitellogenin synthesis exhibit a close correspondence from 4 to 16 days after administration of estradiol-17beta.", "contents": "In vitro translation and estradiol-17beta induction of Xenopus laevis vitellogenin messenger RNA. Administration of estradiol-17beta to male Xenopus laevis induces synthesis and secretion by the liver of the egg yolk precursor protein vitellogenin. RNA extracted from livers of estradiol-17beta-treated Xenopus laevis directs the synthesis of the entire 200,000-dalton vitellogenin monomer in a cell-free protein synthesizing system derived from rabbit reticulocytes. Vitellogenin synthesized in vitro was isolated and quantitated by indirect immunoprecipitation and identified by comparison to authentic [14C]vitellogenin. The in vitro product and [14C]vitellogenin co-migrate on electrophoresis in sodium dodecyl sulfate-polyacrylamide gels and they exhibit identical immunoprecipitation curves. Xenopus laevis vitellogenin messenger RNA has a sedimentation coefficient of approximately 30 S in sucrose density gradients. It can be purified approximately 60-fold from cell RNA by poly(U)-Sepharose chromatography and therefore appears to contain a polyadenylate sequence. Vitellogenin mRNA and vitellogenin synthesis in vivo could not be detected in unstimulated male Xenopus laevis. The relative rate of vitellogenin synthesis and the level of vitellogenin mRNA were determined at various times following the administration of estradiol-17beta. Vitellogenin synthesis is maximal 12 days after estradiol-17beta administration when it comprises approximately 70% of cell protein synthesis. The level of vitellogenin mRNA and the intracellular rate of vitellogenin synthesis exhibit a close correspondence from 4 to 16 days after administration of estradiol-17beta."} {"id": "PMID:1270439", "title": "Comparative studies of lipase and phospholipase A2 acting on substrate monolayers.", "content": "The kinetic aspects of lipolysis by pancreatic lipase and phospholipase A2 from different sources have been compared using monomolecular films of short chain lipids as the substrates. Phosphatidylcholine monolayers, in contrast to phosphatidylethanolamine and phosphatidylglycerol monolayers, were resistant to hydrolysis by pancreatic lipase. The induction time, measured during pre-steady state conditions, increased abruptly for a given value of the surface pressure. This appears to be due to a degree of lipid packing above which the enzyme no longer can penetrate the lipid film. The existence of an optimum in the velocity versus surface pressure profile is the result of at least two counterbalancing factors. As the surface pressure increases, the amount of enzyme present in the interface decreases, whereas the minimal specific activity of the enzyme increases. From this study with monolayers we can conclude that activity of lipolytic enzymes used as tools for probing biological membranes will be greatly influenced by the physiochemical nature of the membrane-water interface. Thus, studies such as this one which can measure the penetrating ability of various lipolytic enzymes can be useful in deriving a better understanding of biological membrane structure.", "contents": "Comparative studies of lipase and phospholipase A2 acting on substrate monolayers. The kinetic aspects of lipolysis by pancreatic lipase and phospholipase A2 from different sources have been compared using monomolecular films of short chain lipids as the substrates. Phosphatidylcholine monolayers, in contrast to phosphatidylethanolamine and phosphatidylglycerol monolayers, were resistant to hydrolysis by pancreatic lipase. The induction time, measured during pre-steady state conditions, increased abruptly for a given value of the surface pressure. This appears to be due to a degree of lipid packing above which the enzyme no longer can penetrate the lipid film. The existence of an optimum in the velocity versus surface pressure profile is the result of at least two counterbalancing factors. As the surface pressure increases, the amount of enzyme present in the interface decreases, whereas the minimal specific activity of the enzyme increases. From this study with monolayers we can conclude that activity of lipolytic enzymes used as tools for probing biological membranes will be greatly influenced by the physiochemical nature of the membrane-water interface. Thus, studies such as this one which can measure the penetrating ability of various lipolytic enzymes can be useful in deriving a better understanding of biological membrane structure."} {"id": "PMID:1270440", "title": "The folding pathway of reduced lysozyme.", "content": "Studies on the mechanism of the glutathione regeneration (Saxena, V.P., and Wetlaufer, D.B. (1970) Biochemistry 9, 5015-5023) of hen egg lysozyme have been carried out. The first two stoichiometric disulfides in lysozyme are formed about 8 times more rapidly than the second two. Almost no enzymic activity is regained until the first two disulfides are formed, thus ruling out an all-or-none mechanism. The disulfide peptides formed early in the regeneration have been isolated and identified. The results show a limited search of folding intermediates, and outline a folding pathway. The early disulfides involve cysteinyl residues III, IV, V, and VI. At the same time cysteinyl residues I, II, VII, and VIII are still reduced, as demonstrated by their isolation as S-alkylated derivatives. At slightly later times a peptide is found which contains the (native) disulfide between cysteinyl residues II and VII. It is likely, but as yet unproven, that formation of disulfide I-VIII completes the cross-linking of lysozyme.", "contents": "The folding pathway of reduced lysozyme. Studies on the mechanism of the glutathione regeneration (Saxena, V.P., and Wetlaufer, D.B. (1970) Biochemistry 9, 5015-5023) of hen egg lysozyme have been carried out. The first two stoichiometric disulfides in lysozyme are formed about 8 times more rapidly than the second two. Almost no enzymic activity is regained until the first two disulfides are formed, thus ruling out an all-or-none mechanism. The disulfide peptides formed early in the regeneration have been isolated and identified. The results show a limited search of folding intermediates, and outline a folding pathway. The early disulfides involve cysteinyl residues III, IV, V, and VI. At the same time cysteinyl residues I, II, VII, and VIII are still reduced, as demonstrated by their isolation as S-alkylated derivatives. At slightly later times a peptide is found which contains the (native) disulfide between cysteinyl residues II and VII. It is likely, but as yet unproven, that formation of disulfide I-VIII completes the cross-linking of lysozyme."} {"id": "PMID:1270441", "title": "Formation of three-dimensional structure in protein fragments. Reactivation of reduced hen egg lysozyme fragment 1-127.", "content": "Regeneration of enzymic activity from reduced hen egg lysozyme peptide 1-127 was effected with a glutathione oxidation-reduction buffer. The rate of regeneration was nearly as great for peptide 1-127 as for reduced lysozyme itself, and the yields were the same (greater than 80%). The regenerated fragment 1-127 was shown to be indistinguishable from fragment 1-127 before reduction by ion exchange chromatography, amino acid analysis, polyacrylamide gel electrophoresis, and disulfide analysis. These results show that the COOH-terminal dipeptide Arg-Leu is not essential for the acquisition of the native three-dimensional structure of lysozyme.", "contents": "Formation of three-dimensional structure in protein fragments. Reactivation of reduced hen egg lysozyme fragment 1-127. Regeneration of enzymic activity from reduced hen egg lysozyme peptide 1-127 was effected with a glutathione oxidation-reduction buffer. The rate of regeneration was nearly as great for peptide 1-127 as for reduced lysozyme itself, and the yields were the same (greater than 80%). The regenerated fragment 1-127 was shown to be indistinguishable from fragment 1-127 before reduction by ion exchange chromatography, amino acid analysis, polyacrylamide gel electrophoresis, and disulfide analysis. These results show that the COOH-terminal dipeptide Arg-Leu is not essential for the acquisition of the native three-dimensional structure of lysozyme."} {"id": "PMID:1270442", "title": "Stimulation of 25-hydroxyvitamin D3-1alpha-hydroxylase by phosphate depletion.", "content": "The ability of low phosphorus diets to stimulate the activity of the 25-hydroxyvitamin D3-1alpha-hydroxylase was tested in the chick. Feeding low phosphorus diets for 2 weeks resulted in a marked increase in enzyme activity relative to chicks fed a normal phosphorus diet. Stimulation of the 25-hydroxyvitamin D3-1alpha-hydroxylase activity by low phosphorus diets, however, was not as great as that observed with a low calcium diet. The low phosphorus and low calcium diets probably results from increased 1,25-dihydroxyvitamin D3 synthesis, whereas the stimulation by phosphate deprivation is only partly the result of increased 1,25-dihydroxyvitamin D3 production.", "contents": "Stimulation of 25-hydroxyvitamin D3-1alpha-hydroxylase by phosphate depletion. The ability of low phosphorus diets to stimulate the activity of the 25-hydroxyvitamin D3-1alpha-hydroxylase was tested in the chick. Feeding low phosphorus diets for 2 weeks resulted in a marked increase in enzyme activity relative to chicks fed a normal phosphorus diet. Stimulation of the 25-hydroxyvitamin D3-1alpha-hydroxylase activity by low phosphorus diets, however, was not as great as that observed with a low calcium diet. The low phosphorus and low calcium diets probably results from increased 1,25-dihydroxyvitamin D3 synthesis, whereas the stimulation by phosphate deprivation is only partly the result of increased 1,25-dihydroxyvitamin D3 production."} {"id": "PMID:1270443", "title": "Preliminary x-ray investigation of an orthorhombic crystal form of human plasma albumin.", "content": "An orthorhombic form of single crystals of human plasma albumin, suitable for x-ray diffraction studies, has been grown with ammonium sulfate from protein solutions purified from fresh frozen single donor plasma as well as from a commercial sample of plasma albumin. The space group is P2(1)2(1)2 with 12 molecules in the unit cell. The cell dimensions are: a = 133.3 +/- 1.2 A, b = 274.8 +/- 3.3 A,, and c = 58.02 +/- 0.02 A.", "contents": "Preliminary x-ray investigation of an orthorhombic crystal form of human plasma albumin. An orthorhombic form of single crystals of human plasma albumin, suitable for x-ray diffraction studies, has been grown with ammonium sulfate from protein solutions purified from fresh frozen single donor plasma as well as from a commercial sample of plasma albumin. The space group is P2(1)2(1)2 with 12 molecules in the unit cell. The cell dimensions are: a = 133.3 +/- 1.2 A, b = 274.8 +/- 3.3 A,, and c = 58.02 +/- 0.02 A."} {"id": "PMID:1270444", "title": "On the 4'-phosphopantetheine content of chicken and rat liver fatty acid synthetases.", "content": "The finding that animal synthetases are complexes consisting of two polypeptide chains (Stoops, J.K., Arslanian, M.J., Oh, Y.H., Vanaman, T.C., and Wakil, S.J. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 1940-1944) led us to investigate their 4'-phosphopantetheine content. We have found that the chicken and rat synthetases contain 1.6 to 2.2 mol of 4'-phosphopantetheine per mol of the complex. The implications of this finding concerning the structure of the complex and the biosynthetic pathway of fatty acid synthesis are discussed.", "contents": "On the 4'-phosphopantetheine content of chicken and rat liver fatty acid synthetases. The finding that animal synthetases are complexes consisting of two polypeptide chains (Stoops, J.K., Arslanian, M.J., Oh, Y.H., Vanaman, T.C., and Wakil, S.J. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 1940-1944) led us to investigate their 4'-phosphopantetheine content. We have found that the chicken and rat synthetases contain 1.6 to 2.2 mol of 4'-phosphopantetheine per mol of the complex. The implications of this finding concerning the structure of the complex and the biosynthetic pathway of fatty acid synthesis are discussed."} {"id": "PMID:1270453", "title": "Preliminary observations of bone ingrowth into porous materials.", "content": "A preliminary investigation has been performed (a) to determine the kinetics of bone ingrowth into porous materials and to determine if this ingrowth could be catalyzed by the presence of a foreign substrate; and (b) to measure the bonding capability of bone with a porous-surfaced metallic implant. Tests on porous-surfaced implants corroborate the work of other investigators in showing that bony tissue will grow into a porous substance that has pores large enough to support tissue nourishment. The shear strength of the bone-implant interface appears to increase with pore size and time of healing. Furthermore, it may be possible to catalyze this tissue ingrowth by the introduction into the fracture site of a foreign substance; in this experiment, glass beads 200-290mu in diameter were used.", "contents": "Preliminary observations of bone ingrowth into porous materials. A preliminary investigation has been performed (a) to determine the kinetics of bone ingrowth into porous materials and to determine if this ingrowth could be catalyzed by the presence of a foreign substrate; and (b) to measure the bonding capability of bone with a porous-surfaced metallic implant. Tests on porous-surfaced implants corroborate the work of other investigators in showing that bony tissue will grow into a porous substance that has pores large enough to support tissue nourishment. The shear strength of the bone-implant interface appears to increase with pore size and time of healing. Furthermore, it may be possible to catalyze this tissue ingrowth by the introduction into the fracture site of a foreign substance; in this experiment, glass beads 200-290mu in diameter were used."} {"id": "PMID:1270454", "title": "The effects of pylon shape on bone-pylon interface performance in direct skeletal attachment.", "content": "The attachment of a prosthesis directly to the part of the skeleton remaining after an amputation offers many improvements over coupling schemes used in conventional prostheses. However, the stresses induced in the bone by the macrostructure of the attached prosthetic device must first be understood because they are a significant consideration in the design of a successful direct skeletal attachment (DSA) system. This investigation utilizes the finite element method of analysis to structurally model some possible DSA systems. Static stress-response models for an above-the-knee human femoral amputation are formulated to investigate the effect of variations in pylon macrostructure on system performance. The models approximate the initial stages of support following the insertion of a pylon into the medullary cavity of the bone and are also used to assess the bond strengths that must be developed between the bone and pylon for a \"no-slip\" condition to hold at their interface. The analyses indicate that either a shaped, marrow cavity-fit pylon or four 135 degree wedges with a complementary pylon are favorable geometries for a DSA system. The stress levels caused by these two geometries are on the order of 20% of the axial compressive strength of cortical bone. For each, local stress levels at the bone-biomaterial interface remain the critical parameters for investigation.", "contents": "The effects of pylon shape on bone-pylon interface performance in direct skeletal attachment. The attachment of a prosthesis directly to the part of the skeleton remaining after an amputation offers many improvements over coupling schemes used in conventional prostheses. However, the stresses induced in the bone by the macrostructure of the attached prosthetic device must first be understood because they are a significant consideration in the design of a successful direct skeletal attachment (DSA) system. This investigation utilizes the finite element method of analysis to structurally model some possible DSA systems. Static stress-response models for an above-the-knee human femoral amputation are formulated to investigate the effect of variations in pylon macrostructure on system performance. The models approximate the initial stages of support following the insertion of a pylon into the medullary cavity of the bone and are also used to assess the bond strengths that must be developed between the bone and pylon for a \"no-slip\" condition to hold at their interface. The analyses indicate that either a shaped, marrow cavity-fit pylon or four 135 degree wedges with a complementary pylon are favorable geometries for a DSA system. The stress levels caused by these two geometries are on the order of 20% of the axial compressive strength of cortical bone. For each, local stress levels at the bone-biomaterial interface remain the critical parameters for investigation."} {"id": "PMID:1270456", "title": "Tissue response to implanted polymers: the significance of sample shape.", "content": "Studies were designed to demonstrate the need for standardization of shape of samples used as implants to evaluate histotoxicity of polymer materials. Six medical-grade polymers (polypropylene, polyethylene, polyurethane, silicone rubber, poly(vinyl chloride), and Teflon) were extruded as rods with circular-, triangular-, and pentagonal-shaped cross sections, and were implanted in rat gluteal muscles for 14 days. Evaluation of the tissue response was assessed by quantitating cellular lysosomal acid phosphatase enzyme activity by using microspectrophotometry. All triangular-shaped implants showed the highest enzyme activity and cellular response; pentagon shapes showed less, and circular rods showed the lowest activity. The results demonstrate the need for standard sample shape for valid comparative studies of tissue response to implanted polymers.", "contents": "Tissue response to implanted polymers: the significance of sample shape. Studies were designed to demonstrate the need for standardization of shape of samples used as implants to evaluate histotoxicity of polymer materials. Six medical-grade polymers (polypropylene, polyethylene, polyurethane, silicone rubber, poly(vinyl chloride), and Teflon) were extruded as rods with circular-, triangular-, and pentagonal-shaped cross sections, and were implanted in rat gluteal muscles for 14 days. Evaluation of the tissue response was assessed by quantitating cellular lysosomal acid phosphatase enzyme activity by using microspectrophotometry. All triangular-shaped implants showed the highest enzyme activity and cellular response; pentagon shapes showed less, and circular rods showed the lowest activity. The results demonstrate the need for standard sample shape for valid comparative studies of tissue response to implanted polymers."} {"id": "PMID:1270457", "title": "A statistical treatment of fatigue of the cast Co-Cr-Mo prosthesis alloy.", "content": "Fatigue tests have been conducted on commercially produced cast Co-Cr-Mo alloy in tension-tension while surrounded by a physiological solution at 37 degrees C. The data have been analyzed by statistical techniques to yield an allowable stress such that there is 95% confidence of less than one failure in 1,000 after 5 X 10(7) cycles of stress fluctuation. These results are valid for a substantially sounder material than may be common in commercial use and therefore a more conservative allowable stress probably ought to be used for design purposes.", "contents": "A statistical treatment of fatigue of the cast Co-Cr-Mo prosthesis alloy. Fatigue tests have been conducted on commercially produced cast Co-Cr-Mo alloy in tension-tension while surrounded by a physiological solution at 37 degrees C. The data have been analyzed by statistical techniques to yield an allowable stress such that there is 95% confidence of less than one failure in 1,000 after 5 X 10(7) cycles of stress fluctuation. These results are valid for a substantially sounder material than may be common in commercial use and therefore a more conservative allowable stress probably ought to be used for design purposes."} {"id": "PMID:1270458", "title": "Mechanism of failure of biocompatible-treated surfaces.", "content": "In recent years, significant advances have been made in treating surfaces to enhance their biocompatibility. This has generally involved the chemical attachmet of very thin molecular coatings to a substrate. Because failure of coated surfaces occurs often, an investigation of the stability of one such molecular coating was undertaken. The specific system studied is a polytetrafluoroethylene polymer (Teflon) with organic macromolecules of heparin ionically bonded to the polymer through use of an intermediate bonding agent. Polymers properly treated in this fashion have been shown to have excellent antithrombogenic properties. To investigate the molecular stability of the heparin coating, the surface heparin concentration of a properly coated sample was reduced by using three different methods: exposure of bonding agent to a suitable solvent; mechanical flexing; and ultrasonic vibration in saline solution...", "contents": "Mechanism of failure of biocompatible-treated surfaces. In recent years, significant advances have been made in treating surfaces to enhance their biocompatibility. This has generally involved the chemical attachmet of very thin molecular coatings to a substrate. Because failure of coated surfaces occurs often, an investigation of the stability of one such molecular coating was undertaken. The specific system studied is a polytetrafluoroethylene polymer (Teflon) with organic macromolecules of heparin ionically bonded to the polymer through use of an intermediate bonding agent. Polymers properly treated in this fashion have been shown to have excellent antithrombogenic properties. To investigate the molecular stability of the heparin coating, the surface heparin concentration of a properly coated sample was reduced by using three different methods: exposure of bonding agent to a suitable solvent; mechanical flexing; and ultrasonic vibration in saline solution..."} {"id": "PMID:1270459", "title": "Adhesion of platelets to artificial surfaces: effect of red cells.", "content": "Adhesion of platelets to several polymer- and protein-coated glass surfaces has been studied in vitro. The apparatus consists of a cylindrical probe rotating in a test tube containing the platelet medium and allows close control of fluid shear and mass transport. Suspensions of washed pig platelets constitute the basic platelet medium, and can be modified by adding back red cells and plasma proteins. Adhesion is measured via 51Cr-labeling of platelets. In the absence of red cells, identical low levels of adhesion were seen on all surfaces and saturation was reached within 2 min. In the presence of red cells, adhesion was greater. Saturation on all surfaces except fibrinogen and collagen again occurred within 2 min. The adhesion levels on polymer surfaces and glass were indistinguishable, while those on albumin were lower and those on fibrinogen were higher. Collagen was the most reactive surface. It did not equilibrate within 15 min., and kinetic data indicated a platelet diffusivity strongly dependent on hematocrit. These effects were attributed to rotational and translational motion of the red cells causing increased diffusion and surface-platelet collision energy.", "contents": "Adhesion of platelets to artificial surfaces: effect of red cells. Adhesion of platelets to several polymer- and protein-coated glass surfaces has been studied in vitro. The apparatus consists of a cylindrical probe rotating in a test tube containing the platelet medium and allows close control of fluid shear and mass transport. Suspensions of washed pig platelets constitute the basic platelet medium, and can be modified by adding back red cells and plasma proteins. Adhesion is measured via 51Cr-labeling of platelets. In the absence of red cells, identical low levels of adhesion were seen on all surfaces and saturation was reached within 2 min. In the presence of red cells, adhesion was greater. Saturation on all surfaces except fibrinogen and collagen again occurred within 2 min. The adhesion levels on polymer surfaces and glass were indistinguishable, while those on albumin were lower and those on fibrinogen were higher. Collagen was the most reactive surface. It did not equilibrate within 15 min., and kinetic data indicated a platelet diffusivity strongly dependent on hematocrit. These effects were attributed to rotational and translational motion of the red cells causing increased diffusion and surface-platelet collision energy."} {"id": "PMID:1270460", "title": "Flame-sprayed alumina on stainless steel for possible prosthetic application.", "content": "Various methods of roughening type 316 stainless steel substrate surfaces for flame-spraying alumina (Al2O3) were investigated and tested for the best alumina-to-metal bond strength. Best strength values were obtained by means of roughening via anodic polarization pitting of the stainless steel. Subsequent in vitro testing indicated a severe loss in bond strength following exposure to aerated Ringer's solution. It is suggested that the utilization of flame-sprayed devices has potential in orthopedic prostheses, but precautions must be observed.", "contents": "Flame-sprayed alumina on stainless steel for possible prosthetic application. Various methods of roughening type 316 stainless steel substrate surfaces for flame-spraying alumina (Al2O3) were investigated and tested for the best alumina-to-metal bond strength. Best strength values were obtained by means of roughening via anodic polarization pitting of the stainless steel. Subsequent in vitro testing indicated a severe loss in bond strength following exposure to aerated Ringer's solution. It is suggested that the utilization of flame-sprayed devices has potential in orthopedic prostheses, but precautions must be observed."} {"id": "PMID:1270461", "title": "In vivo degradation of silicone rubber poppets in prosthetic heart valves.", "content": "Dynamic shear modulus G' was measured throughout the volume of three nonvariant silicone rubber poppets which were recovered from aortic prosthetic heart valves that had been implanted for 4 days, 52 days, and 8 years. Similar measurements were obtained for two unused silicone rubber poppets. Although the recovered poppets exhibited no obvious physical evidence of damage, the silicone rubber had undergone in vivo degradation throughout the poppet volume as indicated by decreases in modulus. The measurements also indicate that the poppet surface degrades at a rate faster than the core. Further, comparison with data reported in the literature suggests that the surfaces of variant poppets degrade at a rate faster than the surfaces of nonvariant poppets.", "contents": "In vivo degradation of silicone rubber poppets in prosthetic heart valves. Dynamic shear modulus G' was measured throughout the volume of three nonvariant silicone rubber poppets which were recovered from aortic prosthetic heart valves that had been implanted for 4 days, 52 days, and 8 years. Similar measurements were obtained for two unused silicone rubber poppets. Although the recovered poppets exhibited no obvious physical evidence of damage, the silicone rubber had undergone in vivo degradation throughout the poppet volume as indicated by decreases in modulus. The measurements also indicate that the poppet surface degrades at a rate faster than the core. Further, comparison with data reported in the literature suggests that the surfaces of variant poppets degrade at a rate faster than the surfaces of nonvariant poppets."} {"id": "PMID:1270462", "title": "Total hip replacement without deep infection in a standard operating room.", "content": "In a consecutive series of 298 total hip-joint replacements performed by a single surgeon using a standard operating room, early deep infection was eliminated by simple inexpensive methods of controlling contamination in the operating room. Settling-plate monitoring revealed an average of 4.8 colonies of bacterial growth per hour of exposure. All patients received prophylactic antibiotics. One patient had a superficial wound infection which was controlled with antibiotic therapy. No deep infections were encountered in the 252 hips followed for two to five years after operation. We conclude that total hip arthroplasty can be performed in the standard operating room without undue risk of infection by consistently employing strict measures of operating-room discipline to limit contamination.", "contents": "Total hip replacement without deep infection in a standard operating room. In a consecutive series of 298 total hip-joint replacements performed by a single surgeon using a standard operating room, early deep infection was eliminated by simple inexpensive methods of controlling contamination in the operating room. Settling-plate monitoring revealed an average of 4.8 colonies of bacterial growth per hour of exposure. All patients received prophylactic antibiotics. One patient had a superficial wound infection which was controlled with antibiotic therapy. No deep infections were encountered in the 252 hips followed for two to five years after operation. We conclude that total hip arthroplasty can be performed in the standard operating room without undue risk of infection by consistently employing strict measures of operating-room discipline to limit contamination."} {"id": "PMID:1270463", "title": "Secondarily infected total joint replacements by hematogenous spread.", "content": "Three fatal cases of infections that followed total joint replacement are repoarted, in each of which a hematogenous source of infection was identified. There also were five non-fatal cases presumable arising hematogenously which were reported in the literature. It is emphasized that concomitant disease, including active rheumatoid arthritis, may predispose to this complication.", "contents": "Secondarily infected total joint replacements by hematogenous spread. Three fatal cases of infections that followed total joint replacement are repoarted, in each of which a hematogenous source of infection was identified. There also were five non-fatal cases presumable arising hematogenously which were reported in the literature. It is emphasized that concomitant disease, including active rheumatoid arthritis, may predispose to this complication."} {"id": "PMID:1270464", "title": "Total hip arthroplasty in Paget's disease of the hip.", "content": "For thirty-two patients with Paget's disease of the pelvis, mechanical disruption of the hip joint caused sufficient pain and disability to require total hip-replacement arthroplasty. Three of the patients had had fractures of the femoral neck. No unusual complications were encountered and the results were excellent.", "contents": "Total hip arthroplasty in Paget's disease of the hip. For thirty-two patients with Paget's disease of the pelvis, mechanical disruption of the hip joint caused sufficient pain and disability to require total hip-replacement arthroplasty. Three of the patients had had fractures of the femoral neck. No unusual complications were encountered and the results were excellent."} {"id": "PMID:1270465", "title": "The postoperative management of scoliosis patients treated with Harrington instrumentation and fusion.", "content": "A retrospective study of maintenance of correction as affected by modifications in the management of patients surgically treated for scoliosis showed better results in Group B than in Group A. No supplementary bone was used in the 187 patients in Group A, who were maintained recumbent for three months postoperatively and who wore an underarm body cast for six months. The 177 patients in Group B received autogenous iliac-bone grafts, were allowed to walk seven to ten days postoperatively, and wore an underarm body cast for nine months. By two years postoperatively the patients in Group A had lost an average of 8.3 degrees of correction, and the patients in Group B had lost 4.3 degrees. A pseudarthrosis developed in eight patients in Group A and in one patient in Group B.", "contents": "The postoperative management of scoliosis patients treated with Harrington instrumentation and fusion. A retrospective study of maintenance of correction as affected by modifications in the management of patients surgically treated for scoliosis showed better results in Group B than in Group A. No supplementary bone was used in the 187 patients in Group A, who were maintained recumbent for three months postoperatively and who wore an underarm body cast for six months. The 177 patients in Group B received autogenous iliac-bone grafts, were allowed to walk seven to ten days postoperatively, and wore an underarm body cast for nine months. By two years postoperatively the patients in Group A had lost an average of 8.3 degrees of correction, and the patients in Group B had lost 4.3 degrees. A pseudarthrosis developed in eight patients in Group A and in one patient in Group B."} {"id": "PMID:1270466", "title": "Screw fixation for certain fractures of the phalanges and metacarpals.", "content": "Twenty-one patients with fractures of the bones of the hand were treated by open reduction and internal fixation with compression screws. The firm fixation allowed range-of-motion exercises in most patients to be begun on the third postoperative day. On follow-up mild restriction in digital motion was seen in only one patient, and significant disturbance in joint function was not encountered. In spite of these advantages, the method is indicated in only a small percentage of such fractures. Usually traditional methods of open reduction and internal fixation are preferred when an open procedure is needed. However, oblique and spiral fractures of the proximal phalanx, some fractures with large single articular fragments particularly involving the proximal interphalangeal joint, and appropriate Bennett's fractures are suitable for screw fixation.", "contents": "Screw fixation for certain fractures of the phalanges and metacarpals. Twenty-one patients with fractures of the bones of the hand were treated by open reduction and internal fixation with compression screws. The firm fixation allowed range-of-motion exercises in most patients to be begun on the third postoperative day. On follow-up mild restriction in digital motion was seen in only one patient, and significant disturbance in joint function was not encountered. In spite of these advantages, the method is indicated in only a small percentage of such fractures. Usually traditional methods of open reduction and internal fixation are preferred when an open procedure is needed. However, oblique and spiral fractures of the proximal phalanx, some fractures with large single articular fragments particularly involving the proximal interphalangeal joint, and appropriate Bennett's fractures are suitable for screw fixation."} {"id": "PMID:1270467", "title": "Review and analysis of silicone-rubber metacarpophalangeal implants.", "content": "A series of 530 consecutive arthroplasties using silicone-rubber implants in 119 patients was reviewed. Clinical and roentgenographic evaluations were completed on sixty patients and 254 implants, with an average follow-up of two and a half years; the remaining fifty-nine patients were evaluated by questionnaire. All but three patients had rheumatoid disease, usually with severe deformity, and many of the patients underwent other procedures on the upper extremity; these procedures often precluded early motion after the arthroplasties. Three prostheses (0.6 per cent) were removed because of infection, and reoperation was required in 2.4 per cent of the joints. Detailed clinical follow-up of 254 prostheses revealed the following: for Swanson prosthesis-average motion 38 degrees, fracture rate 26.2 per cent, and recurrence of clinical deformity 11.3 per cent; for Neibauer prostheses-average motion 35 degrees, fracture rate 38.2 per cent, and recurrence of clinical deformity 44.1 per cent. It should be noted that use of early implant types and some variations from the designer's recommended rehabilitation protocols were features of this series.", "contents": "Review and analysis of silicone-rubber metacarpophalangeal implants. A series of 530 consecutive arthroplasties using silicone-rubber implants in 119 patients was reviewed. Clinical and roentgenographic evaluations were completed on sixty patients and 254 implants, with an average follow-up of two and a half years; the remaining fifty-nine patients were evaluated by questionnaire. All but three patients had rheumatoid disease, usually with severe deformity, and many of the patients underwent other procedures on the upper extremity; these procedures often precluded early motion after the arthroplasties. Three prostheses (0.6 per cent) were removed because of infection, and reoperation was required in 2.4 per cent of the joints. Detailed clinical follow-up of 254 prostheses revealed the following: for Swanson prosthesis-average motion 38 degrees, fracture rate 26.2 per cent, and recurrence of clinical deformity 11.3 per cent; for Neibauer prostheses-average motion 35 degrees, fracture rate 38.2 per cent, and recurrence of clinical deformity 44.1 per cent. It should be noted that use of early implant types and some variations from the designer's recommended rehabilitation protocols were features of this series."} {"id": "PMID:1270468", "title": "Congenital longitudinal deficiency of the fibula: follow-up of treatment by Syme amputation.", "content": "Congenital longitudinal deficiency of the fibula presented two major problems in management: severe shortening of the limb and equinovalgus deformity of the ankle and foot. When the deformity was severe, our attempts at reducing the deformities of the foot and ankle with soft-tissue procedures and our attempts at achieving limb-length equality with various lengthening procedures were unsuccessful. Our best results in these patients were achieved with an early Syme amputation. The pattern of the deformity and the determination of the growth inhibition factor in the involved limb now enable us to make an early estimate of the deformity and plan appropriately. Syme amputation is definitive and allows the patient to have nearly normal function of the limb and a prosthesis of excellent appearance.", "contents": "Congenital longitudinal deficiency of the fibula: follow-up of treatment by Syme amputation. Congenital longitudinal deficiency of the fibula presented two major problems in management: severe shortening of the limb and equinovalgus deformity of the ankle and foot. When the deformity was severe, our attempts at reducing the deformities of the foot and ankle with soft-tissue procedures and our attempts at achieving limb-length equality with various lengthening procedures were unsuccessful. Our best results in these patients were achieved with an early Syme amputation. The pattern of the deformity and the determination of the growth inhibition factor in the involved limb now enable us to make an early estimate of the deformity and plan appropriately. Syme amputation is definitive and allows the patient to have nearly normal function of the limb and a prosthesis of excellent appearance."} {"id": "PMID:1270469", "title": "Transfer of tibialis posterior tendon in cerebral palsy.", "content": "Posterior tendon transfer to the dorsum of the foot through the interosseous membrans is an effective procedure for spastic equinovarus deformity. The complications of excessive calcaneal or excessive valgus deformity can be avoided if the transfer is not inserted too tightly with the foot in dorsiflexion and if it is not transferred to a cuboid insertion. Electromyographic activity was demonstrated in some of the transferred muscles during the swing phase of gait. Tendo achillis lengthening in association with posterior tibial transfer must be done judiciously to avoid deformity of the calcaneus.", "contents": "Transfer of tibialis posterior tendon in cerebral palsy. Posterior tendon transfer to the dorsum of the foot through the interosseous membrans is an effective procedure for spastic equinovarus deformity. The complications of excessive calcaneal or excessive valgus deformity can be avoided if the transfer is not inserted too tightly with the foot in dorsiflexion and if it is not transferred to a cuboid insertion. Electromyographic activity was demonstrated in some of the transferred muscles during the swing phase of gait. Tendo achillis lengthening in association with posterior tibial transfer must be done judiciously to avoid deformity of the calcaneus."} {"id": "PMID:1270470", "title": "Passive motion of the elbow joint.", "content": "A previously unreported method of measuring three-dimensional motion of joints, applied to two elbows obtained post mortem, showed that during flexion there is a continuous and linear change in the carrying angle, the forearm going into varus angulation as elbow flexion progresses. In addition, internal axial rotation of the forearm occurs near the beginning and external axial rotation, toward the end of flexion. With the elbow extended, the ulna shows little tendency to deviate laterally or to rotate axially during pronation and supination. The axis of rotation during elbow flexion lies approximately at the center of the trochlea.", "contents": "Passive motion of the elbow joint. A previously unreported method of measuring three-dimensional motion of joints, applied to two elbows obtained post mortem, showed that during flexion there is a continuous and linear change in the carrying angle, the forearm going into varus angulation as elbow flexion progresses. In addition, internal axial rotation of the forearm occurs near the beginning and external axial rotation, toward the end of flexion. With the elbow extended, the ulna shows little tendency to deviate laterally or to rotate axially during pronation and supination. The axis of rotation during elbow flexion lies approximately at the center of the trochlea."} {"id": "PMID:1270471", "title": "The permeability of articular cartilage under compressive strain and at high pressures.", "content": "The permeability of bovine articular cartilage was measured in an apparatus designed to permit this measurement while the fluid pressure gradient across the cartilage and the axial compressive strain applied to the cartilage were varied independently. For all of the pressure gradients tested the permeability of the cartilage decreased as the compressive strain increased. From previous work, it was postulated that joint lubrication is accomplished first by fluid exudation into the joint space. both at the leading edge of the moving contact area and between portions of the opposing cartilaginous surfaces, and second by imbibition of the expelled fluid back into the cartilage toward the trailing edge of the contact area caused by the \"elastic\" recovery of the tissue. The present work extends this model to include the condition that the permeability of cartilage is dependent on the extent to which it is deformed.", "contents": "The permeability of articular cartilage under compressive strain and at high pressures. The permeability of bovine articular cartilage was measured in an apparatus designed to permit this measurement while the fluid pressure gradient across the cartilage and the axial compressive strain applied to the cartilage were varied independently. For all of the pressure gradients tested the permeability of the cartilage decreased as the compressive strain increased. From previous work, it was postulated that joint lubrication is accomplished first by fluid exudation into the joint space. both at the leading edge of the moving contact area and between portions of the opposing cartilaginous surfaces, and second by imbibition of the expelled fluid back into the cartilage toward the trailing edge of the contact area caused by the \"elastic\" recovery of the tissue. The present work extends this model to include the condition that the permeability of cartilage is dependent on the extent to which it is deformed."} {"id": "PMID:1270472", "title": "The effect of patellectomy on knee function.", "content": "Thirty-three patients were evaluated after patellectomy for subjective complaints, objective physical findings, quadriceps strength, and knee motion during activities of daily living. Partial and complete patellectomy caused an equal loss of active and passive range of motion. Complete patellectomy resulted in greater ligament instability, quadriceps atrophy, and loss of quadriceps strength compared with partial patellectomy. Complete patellectomy casued a reduction in the degree of stance-phase flexion during level walking and negotiating stairs.", "contents": "The effect of patellectomy on knee function. Thirty-three patients were evaluated after patellectomy for subjective complaints, objective physical findings, quadriceps strength, and knee motion during activities of daily living. Partial and complete patellectomy caused an equal loss of active and passive range of motion. Complete patellectomy resulted in greater ligament instability, quadriceps atrophy, and loss of quadriceps strength compared with partial patellectomy. Complete patellectomy casued a reduction in the degree of stance-phase flexion during level walking and negotiating stairs."} {"id": "PMID:1270473", "title": "Hip fusion utilizing the cobra head plate.", "content": "Sixteen consecutive patients underwent hip fusion with fixation by a cobra head compression plate. In six patients on osteotomy of the innominate bone also was done. Four patients had no osteotomy whatsoever, while in six patients medial displacement of the femur was accomplished by centrally dislocating the femoral head through the acetabulum. This modification made the surgical procedure and postoperative care simpler, and rehabilitation was easily accomplished. All of the hips treated in this series had successful bone fusion. All of the patients were out of bed within the first postoperative week, and ambulation with crutches was begun after the second week.", "contents": "Hip fusion utilizing the cobra head plate. Sixteen consecutive patients underwent hip fusion with fixation by a cobra head compression plate. In six patients on osteotomy of the innominate bone also was done. Four patients had no osteotomy whatsoever, while in six patients medial displacement of the femur was accomplished by centrally dislocating the femoral head through the acetabulum. This modification made the surgical procedure and postoperative care simpler, and rehabilitation was easily accomplished. All of the hips treated in this series had successful bone fusion. All of the patients were out of bed within the first postoperative week, and ambulation with crutches was begun after the second week."} {"id": "PMID:1270475", "title": "Anterior tibial-compartment syndrome complicating fractures of the shaft of the tibia.", "content": "Twenty-five cases of anterior tibial-compartment syndrome in twenty-four patients were seen as complications of fractures of the shaft of the tibia. Six patients had fasciotomy within the first six hours of the onset of their symptoms and signs and all made an uneventful recovery. Eighteen patients, in whom treatment was withheld for an average of eighteen hours, were left with a variety of complications including persistent weakness of dorsiflexion in fourteen, a complete footdrop in three, and the necessity for a below-the-knee amputation in one.", "contents": "Anterior tibial-compartment syndrome complicating fractures of the shaft of the tibia. Twenty-five cases of anterior tibial-compartment syndrome in twenty-four patients were seen as complications of fractures of the shaft of the tibia. Six patients had fasciotomy within the first six hours of the onset of their symptoms and signs and all made an uneventful recovery. Eighteen patients, in whom treatment was withheld for an average of eighteen hours, were left with a variety of complications including persistent weakness of dorsiflexion in fourteen, a complete footdrop in three, and the necessity for a below-the-knee amputation in one."} {"id": "PMID:1270476", "title": "The use of tomography in the assessment of fractures of the tibial plateau.", "content": "Tomography was useful in the preoperative assessment of twenty-one tibial-plateau fractures. It helped in classifying these fractures more precisely, information which is very important if the results of different methods of treatment are to be compared. It demonstrated clearly the extent of fracture depression or displacement, or both, as well as the site of the fracture and the extent of fracture comminution. The findings were confirmed at operation in the thirteen patients who had surgery.", "contents": "The use of tomography in the assessment of fractures of the tibial plateau. Tomography was useful in the preoperative assessment of twenty-one tibial-plateau fractures. It helped in classifying these fractures more precisely, information which is very important if the results of different methods of treatment are to be compared. It demonstrated clearly the extent of fracture depression or displacement, or both, as well as the site of the fracture and the extent of fracture comminution. The findings were confirmed at operation in the thirteen patients who had surgery."} {"id": "PMID:1270485", "title": "Metaphysial dysostosis (Jansen type). Report of a case with long follow-up.", "content": "A case of the Jansen type of metaphysial dysostosis, followed for fifteen years from childhood to the age of nineteen, is reported. Radiographs taken at five years revealed the characteristic metaphysial changes in all the tubular bones, especially those of the hands and feet. The acetabular and glenoid areas, the costochondral junctions and the sternal ends of the clavicles were also involved. Radiographs taken at nineteen years, however, showed only marked deformities, which shows that the involvement of the metaphyses can regress by the end of growth. Biopsy of the lower end of radius at the age of twelve revealed changes in the growth plate or physis, especially in the zone of resting cartilage. This finding suggests that cellular function in this zone is disturbed by some unknown mechanism. Hence, the term physial dysostosis may be more accurate than metaphysial dysostosis.", "contents": "Metaphysial dysostosis (Jansen type). Report of a case with long follow-up. A case of the Jansen type of metaphysial dysostosis, followed for fifteen years from childhood to the age of nineteen, is reported. Radiographs taken at five years revealed the characteristic metaphysial changes in all the tubular bones, especially those of the hands and feet. The acetabular and glenoid areas, the costochondral junctions and the sternal ends of the clavicles were also involved. Radiographs taken at nineteen years, however, showed only marked deformities, which shows that the involvement of the metaphyses can regress by the end of growth. Biopsy of the lower end of radius at the age of twelve revealed changes in the growth plate or physis, especially in the zone of resting cartilage. This finding suggests that cellular function in this zone is disturbed by some unknown mechanism. Hence, the term physial dysostosis may be more accurate than metaphysial dysostosis."} {"id": "PMID:1270486", "title": "Protection from stress in bone and its effects. Experiments with stainless steel and plastic plates in dogs.", "content": "In a preliminary experiment the paired radii and femora of dogs were tested for bone mineral mass and mechanical properties including the load at break, the ultimate bending strength and the modulus of elasticity; symmetry was observed for most of the parameters determined. The influence of the elasticity of materials used for the internal splintage of bone and its relationship to bone remodeling were then investigated for stainless steel and plastic plates applied to the femora of dogs. A significant decrease in bone mineral mass per centimetre length of bone and in mechanical properties was demonstrated for the femora plated with steel, and microradiography showed that this was due to massive endosteal resorption. A model for determining the influence of protection from stress in bone is presented.", "contents": "Protection from stress in bone and its effects. Experiments with stainless steel and plastic plates in dogs. In a preliminary experiment the paired radii and femora of dogs were tested for bone mineral mass and mechanical properties including the load at break, the ultimate bending strength and the modulus of elasticity; symmetry was observed for most of the parameters determined. The influence of the elasticity of materials used for the internal splintage of bone and its relationship to bone remodeling were then investigated for stainless steel and plastic plates applied to the femora of dogs. A significant decrease in bone mineral mass per centimetre length of bone and in mechanical properties was demonstrated for the femora plated with steel, and microradiography showed that this was due to massive endosteal resorption. A model for determining the influence of protection from stress in bone is presented."} {"id": "PMID:1270487", "title": "Infection of intervertebral discs after operation.", "content": "Infection of the intervertebral space is a rare complication of operation on the disc (Ford and Key 1955). It occurred in five cases in a series of 650 operations for lumbar disc protrusion done by two of the authors of this paper--an incidence of 0-8%. Symptoms began between seven and twelve days after operation. After initial relief of the original sciatic pain, the patients developed severe back pain and muscle cramps in the legs. Straight-leg raising became much more limited than before operation. The erythrocyte sedimentation rate was raised in all cases. The diagnosis was confirmed by rescreening the Myodil, when an indentation was seen opposite the intervertebral space from which the disc had been excised. Early removal of infected material from the disc space resulted in complete relief of pain and cure of the infection.", "contents": "Infection of intervertebral discs after operation. Infection of the intervertebral space is a rare complication of operation on the disc (Ford and Key 1955). It occurred in five cases in a series of 650 operations for lumbar disc protrusion done by two of the authors of this paper--an incidence of 0-8%. Symptoms began between seven and twelve days after operation. After initial relief of the original sciatic pain, the patients developed severe back pain and muscle cramps in the legs. Straight-leg raising became much more limited than before operation. The erythrocyte sedimentation rate was raised in all cases. The diagnosis was confirmed by rescreening the Myodil, when an indentation was seen opposite the intervertebral space from which the disc had been excised. Early removal of infected material from the disc space resulted in complete relief of pain and cure of the infection."} {"id": "PMID:1270488", "title": "Periosteal pedicle grafting in dogs.", "content": "An experimental model was designed to find a theoretical solution to the clinical problem of congenital tibial pseudarthrosis in children. The osteogenic properties of periosteum having been accepted, paired pedicled flaps of periosteum were raised from the subcutaneous surface of the tibia, tubed and anastomosed in a series of young dogs. In the last twenty-four consecutive cases the rate of complete ossification in these tubes rose to one in three. In the later stages of the work, in addition to the construction of periosteal tube grafts, pseudarthroses were induced in the middle third of each canine tibia in order to see if hypertrophy would occur under the stress of weight-bearing. It was found that in each of twenty-four specimens some hypertrophy occurred in the ossified periosteal tube grafts, and in three of the specimens this hypertrophy was associated with complete ossification of the graft that by-passed the pseudarthrosis.", "contents": "Periosteal pedicle grafting in dogs. An experimental model was designed to find a theoretical solution to the clinical problem of congenital tibial pseudarthrosis in children. The osteogenic properties of periosteum having been accepted, paired pedicled flaps of periosteum were raised from the subcutaneous surface of the tibia, tubed and anastomosed in a series of young dogs. In the last twenty-four consecutive cases the rate of complete ossification in these tubes rose to one in three. In the later stages of the work, in addition to the construction of periosteal tube grafts, pseudarthroses were induced in the middle third of each canine tibia in order to see if hypertrophy would occur under the stress of weight-bearing. It was found that in each of twenty-four specimens some hypertrophy occurred in the ossified periosteal tube grafts, and in three of the specimens this hypertrophy was associated with complete ossification of the graft that by-passed the pseudarthrosis."} {"id": "PMID:1270489", "title": "Remodelling by asymmetrical epiphysial growth. An experimental study in dogs.", "content": "Spontaneous correction of deformity is produced by bone remodelling during the period of growth. The purpose of this experimental study was to find out in which phase and to what extent asymmetrical epiphysial growth participated in the correction of an experimentally produced deformity. Transverse wedge osteotomy was performed in the legs of twenty growing mongrel dogs, the fragments being fixed with bent AO-plates. From radiographs taken at intervals of two weeks the epiphysial and axial angles were measured. Nine dogs were given tetracycline ten to twenty days before death and the cut surfaces were photographed in reflected ultra-violet light. It was found that epiphysial growth played an important role in the remodelling process. This factor accounted for roughly half of the total correction and averaged 12-5 degrees during the observation time of 160 days. The greatest correction occurred during the first weeks. Correction of the epiphysial angle took place with acceleration of growth.", "contents": "Remodelling by asymmetrical epiphysial growth. An experimental study in dogs. Spontaneous correction of deformity is produced by bone remodelling during the period of growth. The purpose of this experimental study was to find out in which phase and to what extent asymmetrical epiphysial growth participated in the correction of an experimentally produced deformity. Transverse wedge osteotomy was performed in the legs of twenty growing mongrel dogs, the fragments being fixed with bent AO-plates. From radiographs taken at intervals of two weeks the epiphysial and axial angles were measured. Nine dogs were given tetracycline ten to twenty days before death and the cut surfaces were photographed in reflected ultra-violet light. It was found that epiphysial growth played an important role in the remodelling process. This factor accounted for roughly half of the total correction and averaged 12-5 degrees during the observation time of 160 days. The greatest correction occurred during the first weeks. Correction of the epiphysial angle took place with acceleration of growth."} {"id": "PMID:1270491", "title": "Subcapital fractures of the femur. A prospective review.", "content": "This abridged account of a report to the British Medical Research Council describes a long-term investigation of 1,503 subcapital fractures of the femur, almost all of which were treated by reduction and internal fixation. With three exceptions, union occurred in all Garden Stage I and Stage II fractures and in 67% of Stage III and Stage IV fractures, of which only 14-5% were united at six months. In women, late segmental collapse was seen after union had occurred in 16% of Stage I and in 27-6% of Stage III and Stage IV fractures. Delay of up to one week before operation had no significant effect on the incidence of non-union or of late segmental collapse. The incidence of union followed by late segmental collapse was higher in women with normal bone density than in those with osteoporosis. Smith-Petersen nailing was found to be the least effective form of fixation in displaced fractures. The age and physical state of the patient, the accuracy of reduction, and the security of fixation had the greatest influence on union.", "contents": "Subcapital fractures of the femur. A prospective review. This abridged account of a report to the British Medical Research Council describes a long-term investigation of 1,503 subcapital fractures of the femur, almost all of which were treated by reduction and internal fixation. With three exceptions, union occurred in all Garden Stage I and Stage II fractures and in 67% of Stage III and Stage IV fractures, of which only 14-5% were united at six months. In women, late segmental collapse was seen after union had occurred in 16% of Stage I and in 27-6% of Stage III and Stage IV fractures. Delay of up to one week before operation had no significant effect on the incidence of non-union or of late segmental collapse. The incidence of union followed by late segmental collapse was higher in women with normal bone density than in those with osteoporosis. Smith-Petersen nailing was found to be the least effective form of fixation in displaced fractures. The age and physical state of the patient, the accuracy of reduction, and the security of fixation had the greatest influence on union."} {"id": "PMID:1270492", "title": "Coxa plana: a radiological comparison of the rate of healing with conservative measures and after osteotomy.", "content": "Subtrochanteric osteotomy has been reported to interrupt the destructive phase of coxa plana and speed up the rate of healing. The aim of this investigation was to test the validity of these statements. The material comprised twenty-five patients treated by osteotomy and thirty-three patients treated by support in a Thomas's splint. For every patient the extent of the radiological changes was estimated and plotted against time as a percentage of the normal epiphysial volume. The graph so obtained represents the rate of destruction and re-ossification, as well as the maximum involvement of the epiphysis. The curves for each group of patients were superimposed in a graph with all the minima coincident in time. The two patterns of curves are closely similar. It was confirmed statistically that the rates of destruction and re-ossification did not differ between the two groups. The results afford no evidence that osteotomy interrupts the disease or speeds up healing.", "contents": "Coxa plana: a radiological comparison of the rate of healing with conservative measures and after osteotomy. Subtrochanteric osteotomy has been reported to interrupt the destructive phase of coxa plana and speed up the rate of healing. The aim of this investigation was to test the validity of these statements. The material comprised twenty-five patients treated by osteotomy and thirty-three patients treated by support in a Thomas's splint. For every patient the extent of the radiological changes was estimated and plotted against time as a percentage of the normal epiphysial volume. The graph so obtained represents the rate of destruction and re-ossification, as well as the maximum involvement of the epiphysis. The curves for each group of patients were superimposed in a graph with all the minima coincident in time. The two patterns of curves are closely similar. It was confirmed statistically that the rates of destruction and re-ossification did not differ between the two groups. The results afford no evidence that osteotomy interrupts the disease or speeds up healing."} {"id": "PMID:1270493", "title": "A controlled study of the indications for and the results of femoral osteotomy in Perthes' disease.", "content": "We have considered the reasons for securing containment of the femoral head in Perthes' disease and have reviewed briefly the methods used. The present investigation describes the outcome in a controlled series of forty-eight hips treated by containment by femoral varus-rotation osteotomy in selected patients. In assessing the results we have emphasised that controls are essential, and for this purpose we have used two comparable groups, one untreated and the other treated by methods other than containment. The same factors were considered in assessment--namely age, duration, group, and the presence or absence of \"at risk\" signs. The results were graded similarly as good, fair and poor in all groups. We have concluded that containment by femoral osteotomy is the treatment of choice in patients with \"at risk\" signs provided that severe deformity has not already occurred. There is no evidence that treatment of any kind favourably influences the course of the disorder in the remainder. Although this is predominantly a radiological study some clinical features are discussed.", "contents": "A controlled study of the indications for and the results of femoral osteotomy in Perthes' disease. We have considered the reasons for securing containment of the femoral head in Perthes' disease and have reviewed briefly the methods used. The present investigation describes the outcome in a controlled series of forty-eight hips treated by containment by femoral varus-rotation osteotomy in selected patients. In assessing the results we have emphasised that controls are essential, and for this purpose we have used two comparable groups, one untreated and the other treated by methods other than containment. The same factors were considered in assessment--namely age, duration, group, and the presence or absence of \"at risk\" signs. The results were graded similarly as good, fair and poor in all groups. We have concluded that containment by femoral osteotomy is the treatment of choice in patients with \"at risk\" signs provided that severe deformity has not already occurred. There is no evidence that treatment of any kind favourably influences the course of the disorder in the remainder. Although this is predominantly a radiological study some clinical features are discussed."} {"id": "PMID:1270494", "title": "Late open reduction of traumatic dislocation of the hip. Report of three cases.", "content": "Three patients were reviewed seven, eight and fourteen years after delayed open reduction of traumatic posterior dislocation of the hip. The delay between injury and operation varied from twenty-eight to ninety-three days. At the time of review symptoms were minimal or absent, and in all cases the injured hip was clinically normal. Radiological examination showed loss of articular cartilage in one hip and trabecular changes in the bone of all three. On the basis of these three results the traditional pessimism about prognosis in such cases may not be justified.", "contents": "Late open reduction of traumatic dislocation of the hip. Report of three cases. Three patients were reviewed seven, eight and fourteen years after delayed open reduction of traumatic posterior dislocation of the hip. The delay between injury and operation varied from twenty-eight to ninety-three days. At the time of review symptoms were minimal or absent, and in all cases the injured hip was clinically normal. Radiological examination showed loss of articular cartilage in one hip and trabecular changes in the bone of all three. On the basis of these three results the traditional pessimism about prognosis in such cases may not be justified."} {"id": "PMID:1270495", "title": "Excision arthroplasty of the hip.", "content": "The results of excision arthroplasty on forty hips in thirty-two patients have been studied by personal review. The mean follow-up was ten years and the results were graded in the Lazansky system. The outcome was fairly predictable, most patients achieving a fair to good result. The patients were satisfied with the operation in unilateral cases as a secondary operation, but it was generally unsatisfactory as a primary procedure or when performed bilaterally. Pain relief was satisfactory, and previously infected hips achieved sound wound and bone healing. Half could walk with no aid or one stick. No correlation could be found between the radiological appearances and the quality of the result.", "contents": "Excision arthroplasty of the hip. The results of excision arthroplasty on forty hips in thirty-two patients have been studied by personal review. The mean follow-up was ten years and the results were graded in the Lazansky system. The outcome was fairly predictable, most patients achieving a fair to good result. The patients were satisfied with the operation in unilateral cases as a secondary operation, but it was generally unsatisfactory as a primary procedure or when performed bilaterally. Pain relief was satisfactory, and previously infected hips achieved sound wound and bone healing. Half could walk with no aid or one stick. No correlation could be found between the radiological appearances and the quality of the result."} {"id": "PMID:1270496", "title": "Treatment of scoliosis by posterior fusion, Harrington instrumentation and early walking.", "content": "One hundred and three patients with scoliosis treated by posterior fusion and Harrington instrumentation are reviewed. The fusion technique described does not require added bone. Walking in a localiser plaster is encouraged as soon as the wound is healed, usually two weeks after operation. The results compare satisfactorily with others published. It is concluded that added bone is not necessary unless neural arch defects are present, and that early walking is advantageous and without risk to the correction.", "contents": "Treatment of scoliosis by posterior fusion, Harrington instrumentation and early walking. One hundred and three patients with scoliosis treated by posterior fusion and Harrington instrumentation are reviewed. The fusion technique described does not require added bone. Walking in a localiser plaster is encouraged as soon as the wound is healed, usually two weeks after operation. The results compare satisfactorily with others published. It is concluded that added bone is not necessary unless neural arch defects are present, and that early walking is advantageous and without risk to the correction."} {"id": "PMID:1270497", "title": "The rib hump in idiopathic scoliosis. Measurement, analysis and response to treatment.", "content": "This paper describes a simple method for the recording of rib deformity in idiopathic scoliosis. The relationships have been recorded between the measured rib hump and rib depression deformities and 1) the rotation of the vertebral bodies (as measured by the method of Nash and Moe on the standing radiograph); 2) the degree of lateral curvature (as measured by the method of Cobb on the standing radiograph); and 3) the rib-vertebra angles and their differences (as described by Mehta). No clear linear relationships were found. Many examples of irregular relationship were recorded, for example, marked spinal rotation with minimal rib hump. The response of the rib deformities to treatment by Milwaukee brace in fifty-two patients is described; the hump is little changed but the depression on the opposite side may be considerably reduced. Harrington instrumentation may have a similar effect.", "contents": "The rib hump in idiopathic scoliosis. Measurement, analysis and response to treatment. This paper describes a simple method for the recording of rib deformity in idiopathic scoliosis. The relationships have been recorded between the measured rib hump and rib depression deformities and 1) the rotation of the vertebral bodies (as measured by the method of Nash and Moe on the standing radiograph); 2) the degree of lateral curvature (as measured by the method of Cobb on the standing radiograph); and 3) the rib-vertebra angles and their differences (as described by Mehta). No clear linear relationships were found. Many examples of irregular relationship were recorded, for example, marked spinal rotation with minimal rib hump. The response of the rib deformities to treatment by Milwaukee brace in fifty-two patients is described; the hump is little changed but the depression on the opposite side may be considerably reduced. Harrington instrumentation may have a similar effect."} {"id": "PMID:1270498", "title": "The management of thoracic and thoraco-lumbar injuries of the spine with neurological involvement.", "content": "The results of treatment of injuries of the thoracic and thoraco-lumbar spine with neurological involvement have been reviewed in a retrospective study of 115 patients, of whom eighty-nine received conservative and twenty-six surgical treatment. Operation was reserved, in general, for patients with irreducible dislocations and incomplete neurological lesions, open reduction and internal fixation being the commonest procedure. Only three patients required a delayed spinal fusion for suspected instability after a period of conservative treatment. On the other hand, ten patients, eight of whom had been treated surgically, were left with severe chronic spinal pain. Of the patients treated conservatively, 35% showed significant neurological improvement compared to 38% of those treated surgically, but the latter group contained a much higher proportion of incomplete lesions with a far better prognosis. It is concluded that the place for early operation might be still further restricted.", "contents": "The management of thoracic and thoraco-lumbar injuries of the spine with neurological involvement. The results of treatment of injuries of the thoracic and thoraco-lumbar spine with neurological involvement have been reviewed in a retrospective study of 115 patients, of whom eighty-nine received conservative and twenty-six surgical treatment. Operation was reserved, in general, for patients with irreducible dislocations and incomplete neurological lesions, open reduction and internal fixation being the commonest procedure. Only three patients required a delayed spinal fusion for suspected instability after a period of conservative treatment. On the other hand, ten patients, eight of whom had been treated surgically, were left with severe chronic spinal pain. Of the patients treated conservatively, 35% showed significant neurological improvement compared to 38% of those treated surgically, but the latter group contained a much higher proportion of incomplete lesions with a far better prognosis. It is concluded that the place for early operation might be still further restricted."} {"id": "PMID:1270499", "title": "Strontium 87mSr bone scanning for the evaluation of total hip replacement.", "content": "In a series of seventeen patients with unilateral osteoarthritis of the hip a scintiscanning follow-up study was made before and after total hip replacement for the assessment of the normal course of the 87mSr-scintiscan. In another series of twenty-eight patients with total hip replacement a photoscan was made as a supplement for the diagnosis of loosening of one or both components of a total hip implant. In most of these cases it proved to be a useful method, especially when clinical and raidological examination was inconclusive. It is concluded that up to six months after operation increased osteoblastic activity exists; the scintiscan became normal after that time. 87mSr scintiscanning offers a safe and simple technique for the assessment of the success and stability of total hip arthroplasty. It is also a useful aid for the early detection of loosening and infection. The procedure can help in the differential diagnosis of complaints after total hip replacement.", "contents": "Strontium 87mSr bone scanning for the evaluation of total hip replacement. In a series of seventeen patients with unilateral osteoarthritis of the hip a scintiscanning follow-up study was made before and after total hip replacement for the assessment of the normal course of the 87mSr-scintiscan. In another series of twenty-eight patients with total hip replacement a photoscan was made as a supplement for the diagnosis of loosening of one or both components of a total hip implant. In most of these cases it proved to be a useful method, especially when clinical and raidological examination was inconclusive. It is concluded that up to six months after operation increased osteoblastic activity exists; the scintiscan became normal after that time. 87mSr scintiscanning offers a safe and simple technique for the assessment of the success and stability of total hip arthroplasty. It is also a useful aid for the early detection of loosening and infection. The procedure can help in the differential diagnosis of complaints after total hip replacement."} {"id": "PMID:1270500", "title": "The importance of gastrocnemius recession in the correction of equinus deformity in cerebral palsy.", "content": "Spasm or contracture of the gastrocnemius muscle is predominantly responsible for the equinus deformity of the foot in cerebral palsy. Its release is therefore logical in the treatment of all cases which do not respond to conservative measures. The authors have demonstrated, by the use of metal markers and radiographic control at operation, that adequate release cannot be achieved by severance of the calcaneal tendon alone, and that in order to ensure relaxation of the gastrocnemius muscle, the operation of choice is gastrocnemius recession by the method of Strayer, coupled with lengthening of the calcaneal tendon to deal with such degree of the deformity as may be attributable to shortening of the soleus. A survey of 100 limbs treated by this method revealed a recurrence rate of equinus of 9% and a degree of calcaneus deformity resulting in inadequate push-off in 3% of cases after an average follow-up period of six years.", "contents": "The importance of gastrocnemius recession in the correction of equinus deformity in cerebral palsy. Spasm or contracture of the gastrocnemius muscle is predominantly responsible for the equinus deformity of the foot in cerebral palsy. Its release is therefore logical in the treatment of all cases which do not respond to conservative measures. The authors have demonstrated, by the use of metal markers and radiographic control at operation, that adequate release cannot be achieved by severance of the calcaneal tendon alone, and that in order to ensure relaxation of the gastrocnemius muscle, the operation of choice is gastrocnemius recession by the method of Strayer, coupled with lengthening of the calcaneal tendon to deal with such degree of the deformity as may be attributable to shortening of the soleus. A survey of 100 limbs treated by this method revealed a recurrence rate of equinus of 9% and a degree of calcaneus deformity resulting in inadequate push-off in 3% of cases after an average follow-up period of six years."} {"id": "PMID:1270501", "title": "Local excision of cyst of lateral meniscus of knee without recurrence.", "content": "Twenty-two patients with cysts of the lateral meniscus have been treated by operation. A modified operative procedure is described whereby the meniscus is inspected for a concomitant tear. A tear of the meniscus was found in ten patients and these were treated by meniscectomy. The remaining twelve cases were treated by excision of the cyst only. The rehabilitation period was considerably less in these patients. Recurrence of the cyst did not occur. The rationale for local excision is based on the similarity between the cyst of a meniscus and a simple ganglion, and also on the desirability of preserving the meniscus.", "contents": "Local excision of cyst of lateral meniscus of knee without recurrence. Twenty-two patients with cysts of the lateral meniscus have been treated by operation. A modified operative procedure is described whereby the meniscus is inspected for a concomitant tear. A tear of the meniscus was found in ten patients and these were treated by meniscectomy. The remaining twelve cases were treated by excision of the cyst only. The rehabilitation period was considerably less in these patients. Recurrence of the cyst did not occur. The rationale for local excision is based on the similarity between the cyst of a meniscus and a simple ganglion, and also on the desirability of preserving the meniscus."} {"id": "PMID:1270502", "title": "Disability of the hindfoot after fracture of the tibial shaft.", "content": "Hindfoot (subtalar) movement and disability after fracture of the tibial shaft have been studied. One hundred patients with soundly healed fractures of the tibial shaft treated by immobilisation in a long leg plaster cast were examined at least one year after the fracture had healed. Subtalar movement was accurately measured by a special technique and the patients were questioned specifically about any disability associated with their hindfoot. Subtalar movement was limited to some degree in 72% of patients. Forty-three per cent of patients complained of symptoms related to their subtalar joint and 12% found these symptoms troublesome.", "contents": "Disability of the hindfoot after fracture of the tibial shaft. Hindfoot (subtalar) movement and disability after fracture of the tibial shaft have been studied. One hundred patients with soundly healed fractures of the tibial shaft treated by immobilisation in a long leg plaster cast were examined at least one year after the fracture had healed. Subtalar movement was accurately measured by a special technique and the patients were questioned specifically about any disability associated with their hindfoot. Subtalar movement was limited to some degree in 72% of patients. Forty-three per cent of patients complained of symptoms related to their subtalar joint and 12% found these symptoms troublesome."} {"id": "PMID:1270504", "title": "Long-term follow-up results of the iliofemoral venous thrombosis.", "content": "During the past 7 years 116 patients with acute and chronic iliofemoral venous thrombosis were treated surgically and medically. Exploration was undertaken mainly by clinical assessment and routine venography for follow-up was not considered as a requisite. Thrombectomy was performed 18 times in 17 patients with excellent or good results in 66.6%. Palma's operation was carried out 17 times in 17 patients with satisfactory results in 82.3%. These were contrasted with 34.2% satisfactory results among the medical patients. These lead to the following conclusion: 1. Venous thrombectomy within 14 days after the onset is effective. 2. The usefulness of delayed thrombectomy is uncertain. 3. Palma's operation offers satisfactory results for chronic iliofemoral venous thrombosis. 4. In Japan, in contrast with America and Europe, pulmonary thromboembolism is exceedingly rare and ligation or interruption of the inferior vena cava or the femoral vein is not performed routinely.", "contents": "Long-term follow-up results of the iliofemoral venous thrombosis. During the past 7 years 116 patients with acute and chronic iliofemoral venous thrombosis were treated surgically and medically. Exploration was undertaken mainly by clinical assessment and routine venography for follow-up was not considered as a requisite. Thrombectomy was performed 18 times in 17 patients with excellent or good results in 66.6%. Palma's operation was carried out 17 times in 17 patients with satisfactory results in 82.3%. These were contrasted with 34.2% satisfactory results among the medical patients. These lead to the following conclusion: 1. Venous thrombectomy within 14 days after the onset is effective. 2. The usefulness of delayed thrombectomy is uncertain. 3. Palma's operation offers satisfactory results for chronic iliofemoral venous thrombosis. 4. In Japan, in contrast with America and Europe, pulmonary thromboembolism is exceedingly rare and ligation or interruption of the inferior vena cava or the femoral vein is not performed routinely."} {"id": "PMID:1270503", "title": "Peripheral arterial embolectomy in the aged.", "content": "A series of 65 geriatric patients, operated upon for 76 peripheral arterial embolic events, is presented. The underlying condition was rheumatic heart disease in 8 and arteriosclerotic in 57. No patient was denied surgery unless widespread irreversible ischemia of the limb was present. Limb salvage was accomplished in 35 patients (54%). It was influenced by age, the underlying disease and time elapsed until resumption of circulation to the limb. The mortality rate experienced in this series was very high. 31 patients (48%) died postoperatively, mainly from cardiorespiratory failure. Death was related to the severity of the patients condition before surgery. 29 out of the 34 surviving patients were discharged with a viable limb. The high death rate observed is discussed.", "contents": "Peripheral arterial embolectomy in the aged. A series of 65 geriatric patients, operated upon for 76 peripheral arterial embolic events, is presented. The underlying condition was rheumatic heart disease in 8 and arteriosclerotic in 57. No patient was denied surgery unless widespread irreversible ischemia of the limb was present. Limb salvage was accomplished in 35 patients (54%). It was influenced by age, the underlying disease and time elapsed until resumption of circulation to the limb. The mortality rate experienced in this series was very high. 31 patients (48%) died postoperatively, mainly from cardiorespiratory failure. Death was related to the severity of the patients condition before surgery. 29 out of the 34 surviving patients were discharged with a viable limb. The high death rate observed is discussed."} {"id": "PMID:1270506", "title": "Subendocardial myocardial necrosis: a preventable lesion.", "content": "Left ventricular subendocardial hemorrhagic necrosis, a lesion entirely different from conventional myocardial infarction, has been an important cause of serious morbidity and mortality in open heart surgery, particularly aortic valve replacement. An established experimental model in which this lesion could be consistently produced in calves, was utilized to examine the protective role of hypothermia and/or Solumedrol infusion. Solumedrol infusion and systemic hypothermia were not sufficiently effective in protecting the myocardium against 40 minutes of left coronary artery occlusion during total cardiopulmonary bypass. Profound continuous irrigation of the pericardial cavity with 4 degrees centigrade Ringers lactate solution, with or without Solumedrol infusion, under similar circumstances yielded excellent results, both in terms of myocardial performance and preservation. This experiment has encouraged the clinical use of this technique in our institution.", "contents": "Subendocardial myocardial necrosis: a preventable lesion. Left ventricular subendocardial hemorrhagic necrosis, a lesion entirely different from conventional myocardial infarction, has been an important cause of serious morbidity and mortality in open heart surgery, particularly aortic valve replacement. An established experimental model in which this lesion could be consistently produced in calves, was utilized to examine the protective role of hypothermia and/or Solumedrol infusion. Solumedrol infusion and systemic hypothermia were not sufficiently effective in protecting the myocardium against 40 minutes of left coronary artery occlusion during total cardiopulmonary bypass. Profound continuous irrigation of the pericardial cavity with 4 degrees centigrade Ringers lactate solution, with or without Solumedrol infusion, under similar circumstances yielded excellent results, both in terms of myocardial performance and preservation. This experiment has encouraged the clinical use of this technique in our institution."} {"id": "PMID:1270507", "title": "Detection and treatment of pre-operative coagulation abnormalities in cardiac surgical patients.", "content": "A pre-operative coagulation profile was performed on 10 consecutive patients undergoing open-heart surgery. 16.3% of patients had at least one abnormal result. The most common abnormality was found in the partial thromboplastin time system. All patients were treated with replacement of appropriate specific blood products during surgery. These measures prevented significant excess blood loss in the study group as compared to a control group of patients, both at surgery and over a twenty-four hour post-operative period.", "contents": "Detection and treatment of pre-operative coagulation abnormalities in cardiac surgical patients. A pre-operative coagulation profile was performed on 10 consecutive patients undergoing open-heart surgery. 16.3% of patients had at least one abnormal result. The most common abnormality was found in the partial thromboplastin time system. All patients were treated with replacement of appropriate specific blood products during surgery. These measures prevented significant excess blood loss in the study group as compared to a control group of patients, both at surgery and over a twenty-four hour post-operative period."} {"id": "PMID:1270510", "title": "Conservation of ribosomal RNA during compensatory renal hypertrophy. A major mechanism in RNA accretion.", "content": "After removal of one mouse kidney, compensatory hypertrophy in the remaining kidney is marked in 2 days by a 20% average increase in ribosomal RNA (rRNA) per cell. Both 28S and 18S RNA are conserved during the initial stages of compensatory renal hypertrophy to an extent sufficient to account for the rest of the observed accumulation of rRNA. Like some cultured cells, the kidney conserves rRNA during physiological growth.", "contents": "Conservation of ribosomal RNA during compensatory renal hypertrophy. A major mechanism in RNA accretion. After removal of one mouse kidney, compensatory hypertrophy in the remaining kidney is marked in 2 days by a 20% average increase in ribosomal RNA (rRNA) per cell. Both 28S and 18S RNA are conserved during the initial stages of compensatory renal hypertrophy to an extent sufficient to account for the rest of the observed accumulation of rRNA. Like some cultured cells, the kidney conserves rRNA during physiological growth."} {"id": "PMID:1270509", "title": "Support of cardiac performance following heart valve surgery by raising heart rate to the optimal pacing rate.", "content": "Effects of hemodynamic parameters of heart rate were studied in 19 patients with low cardiac output syndrome following open heart surgery for mitral and/or aortic valve replacement in the first five postoperative days. The central venous pressure (CVP), left atrial mean pressure (LAMP), and arterial blood pressures were determined at spontaneous heart rate (SHR), and during graded atrial (12 pts.) or ventricular (7 pts.) pacing each day. An \"optimal pacing rate\" (OPR), characterized by the most advantageous arterial pressures at the possible lowest levels of CVP and LAMP, and by the suppression of preexisting arrhythmias, if any, was established daily for maintaining each patient on that rate. The SHR was 69 +/- 9 and the OPR was 102 +/- 9 on the first postoperative day. For the fifth postoperative day the SHR was 68 +/- 10 and the OPR decreased to 90 +/- 9. Pacing with the OPR significantly increased cardiac performance. E.g. the hemodynamic improvement on the first postoperative day induced by pacing was comparable to the spontaneous improvement seen during the first five postoperative days. The hemodynamic effect of atrial pacing on circulation was more definitive than that of ventricular pacing. Since OPR may be significantly higher than SHR and varies from day to day, we suggest that, in cases where pacing is applied to improve cardiac performance, it be determined for each patient individually each postoperative day.", "contents": "Support of cardiac performance following heart valve surgery by raising heart rate to the optimal pacing rate. Effects of hemodynamic parameters of heart rate were studied in 19 patients with low cardiac output syndrome following open heart surgery for mitral and/or aortic valve replacement in the first five postoperative days. The central venous pressure (CVP), left atrial mean pressure (LAMP), and arterial blood pressures were determined at spontaneous heart rate (SHR), and during graded atrial (12 pts.) or ventricular (7 pts.) pacing each day. An \"optimal pacing rate\" (OPR), characterized by the most advantageous arterial pressures at the possible lowest levels of CVP and LAMP, and by the suppression of preexisting arrhythmias, if any, was established daily for maintaining each patient on that rate. The SHR was 69 +/- 9 and the OPR was 102 +/- 9 on the first postoperative day. For the fifth postoperative day the SHR was 68 +/- 10 and the OPR decreased to 90 +/- 9. Pacing with the OPR significantly increased cardiac performance. E.g. the hemodynamic improvement on the first postoperative day induced by pacing was comparable to the spontaneous improvement seen during the first five postoperative days. The hemodynamic effect of atrial pacing on circulation was more definitive than that of ventricular pacing. Since OPR may be significantly higher than SHR and varies from day to day, we suggest that, in cases where pacing is applied to improve cardiac performance, it be determined for each patient individually each postoperative day."} {"id": "PMID:1270511", "title": "Collagenous bone matrix-induced endochondral ossification hemopoiesis.", "content": "Transplantation of collagenous matrix from the rat diaphyseal bone to subcutaneous sites resulted in new bone formation by an endochondral sequence. Functional bone marrow develops within the newly formed ossicle. On day 1, the implanted matrix was a discrete conglomerate with fibrin clot and polymorphonuclear leukocytes. By day 3, the leukocytes disappeared, and this event was followed by migration and close apposition of fibroblast cell surface to the collagenous matrix. This initial matrix-membrane interaction culminated in differentiation of fibroblasts to chondroblasts and osteoblasts. The calcification of the hypertrophied chondrocytes and new bone formation were correlated with increased alkaline phosphatase activity and 45Ca incorporation. The ingrowth of capillaries on day 9 resulted in chondrolysis and osteogenesis. Further remodelling of bony trabeculae by osteoclasts resulted in an ossicle of cancellous bone. This was followed by emergence of extravascular islands of hemocytoblasts and their differentiation into functional bone marrow with erythropoietic and granulopoietic elements and megakaryocytes in the ossicle. The onset and maintenance of erythropoiesis in the induced bone marrow were monitored by 59Fe incorporation into protein-bound heme. These findings imply a role for extracellular collagenous matrix in cell differentiation.", "contents": "Collagenous bone matrix-induced endochondral ossification hemopoiesis. Transplantation of collagenous matrix from the rat diaphyseal bone to subcutaneous sites resulted in new bone formation by an endochondral sequence. Functional bone marrow develops within the newly formed ossicle. On day 1, the implanted matrix was a discrete conglomerate with fibrin clot and polymorphonuclear leukocytes. By day 3, the leukocytes disappeared, and this event was followed by migration and close apposition of fibroblast cell surface to the collagenous matrix. This initial matrix-membrane interaction culminated in differentiation of fibroblasts to chondroblasts and osteoblasts. The calcification of the hypertrophied chondrocytes and new bone formation were correlated with increased alkaline phosphatase activity and 45Ca incorporation. The ingrowth of capillaries on day 9 resulted in chondrolysis and osteogenesis. Further remodelling of bony trabeculae by osteoclasts resulted in an ossicle of cancellous bone. This was followed by emergence of extravascular islands of hemocytoblasts and their differentiation into functional bone marrow with erythropoietic and granulopoietic elements and megakaryocytes in the ossicle. The onset and maintenance of erythropoiesis in the induced bone marrow were monitored by 59Fe incorporation into protein-bound heme. These findings imply a role for extracellular collagenous matrix in cell differentiation."} {"id": "PMID:1270512", "title": "Developmental changes in mitochondria during the transition into lactation in the mouse mammary gland.", "content": "Mitochondrial biogenesis in the parenchymal cell of the mouse mammary gland appears to occur in two distinct phases: replication during cell proliferation, and maturation during cell differentiation. This study of the mitochondrial maturation phase in the mouse gland demonstrates a significant increase in organelle density on isopycnic sucrose gradient centrifugation during the transition from late pregnancy to day 8 of lactation. Differential fragility to high sucrose concentrations or changes in mitochondrial lipid composition do not satisfactorily explain the density increases. When organelle densities were assessed by centrifugation under iso-osmotic conditions with Ficoll gradients in 0.25 M sucrose, the mitochondria from pregnant glands were observed to be more dense than those from lactating glands. The two mitochondrial populations were also found to differ in their response to changes in sucrose concentration in the Ficoll gradients. When sucrose concentration was increased, the density of both pregnant and lactating gland mitochondria increased nonlinearly, the increase being greater with the lactating gland organelles. By use of mathematical models, the differing response was interpreted as a change in the density and osmotic activity of the mitochondrial internal compartment (inner membrane plus matrix space). We have proposed that the changes reflect a large expansion of the inner mitochondrial membrane and perhaps the matrix material during the transition into lactation in the differentiating parenchymal cell.", "contents": "Developmental changes in mitochondria during the transition into lactation in the mouse mammary gland. Mitochondrial biogenesis in the parenchymal cell of the mouse mammary gland appears to occur in two distinct phases: replication during cell proliferation, and maturation during cell differentiation. This study of the mitochondrial maturation phase in the mouse gland demonstrates a significant increase in organelle density on isopycnic sucrose gradient centrifugation during the transition from late pregnancy to day 8 of lactation. Differential fragility to high sucrose concentrations or changes in mitochondrial lipid composition do not satisfactorily explain the density increases. When organelle densities were assessed by centrifugation under iso-osmotic conditions with Ficoll gradients in 0.25 M sucrose, the mitochondria from pregnant glands were observed to be more dense than those from lactating glands. The two mitochondrial populations were also found to differ in their response to changes in sucrose concentration in the Ficoll gradients. When sucrose concentration was increased, the density of both pregnant and lactating gland mitochondria increased nonlinearly, the increase being greater with the lactating gland organelles. By use of mathematical models, the differing response was interpreted as a change in the density and osmotic activity of the mitochondrial internal compartment (inner membrane plus matrix space). We have proposed that the changes reflect a large expansion of the inner mitochondrial membrane and perhaps the matrix material during the transition into lactation in the differentiating parenchymal cell."} {"id": "PMID:1270513", "title": "Properties of growth-related acetylcholinesterase in a cell line of fibroblastic origin.", "content": "We have previously reported the presence and regulation of an acetylcholine-hydrolyzing enzyme in high density suspension cultures of WRL-10A fibroblasts where its activity increases 100-fold when growth is arrested. Substrate specificity, substrate inhibition, and product identification studies indicate that this enzyme is acetylcholinesterase (AChE, EC 3.1.1.7). Treatment of whole cells with 5 mM diazotized sulfanilic acid revealed that most of the AChE is located on the external surface of the cell membrane. It was also found that the enzyme is released in the medium at a rate of 0.5 U/h/mg cell protein and that within a 24-h period the de novo synthesized and liberated AChE is equivalent to 90% of the activity associated with the cells. No similar synthesis of AChE was found in six order fibroblastic cell lines examined. These and related findings indicating that acetylcholine is also present in high density populations of WRL-10A cells suggest that this unique phenotype may be used profitably in exploring further the relationship between components of the cholinergic system and non-neuronal cell growth.", "contents": "Properties of growth-related acetylcholinesterase in a cell line of fibroblastic origin. We have previously reported the presence and regulation of an acetylcholine-hydrolyzing enzyme in high density suspension cultures of WRL-10A fibroblasts where its activity increases 100-fold when growth is arrested. Substrate specificity, substrate inhibition, and product identification studies indicate that this enzyme is acetylcholinesterase (AChE, EC 3.1.1.7). Treatment of whole cells with 5 mM diazotized sulfanilic acid revealed that most of the AChE is located on the external surface of the cell membrane. It was also found that the enzyme is released in the medium at a rate of 0.5 U/h/mg cell protein and that within a 24-h period the de novo synthesized and liberated AChE is equivalent to 90% of the activity associated with the cells. No similar synthesis of AChE was found in six order fibroblastic cell lines examined. These and related findings indicating that acetylcholine is also present in high density populations of WRL-10A cells suggest that this unique phenotype may be used profitably in exploring further the relationship between components of the cholinergic system and non-neuronal cell growth."} {"id": "PMID:1270514", "title": "Changes in number, mobility, and topographical distribution of lectin receptors during maturation of chick erythroid cells.", "content": "Plant lectins have been used to probe changes in cell surface characteristics that accompny differentiation in a complete series of chick erythroid cells. Dramatic differences in lectin receptor mobility were observed between the most immature cells of the series, the proerythroblasts, and cells at the next stage of maturation, the erythroblasts. Both concanavalin A and Ricinus communis agglutinin form caps on proerythroblasts, whereas they develop a patchy distribution on erythroblasts. Erythroid cells at later developmental stages show a homogeneous distribution of surface-bound R. communis agglutinin. Concanavalin A also shows a uniform distribution on the cell periphery, but appears to be concentrated in a ring above the perinuclear region of the cell. In addition to changes in mobility of lectin receptors, a large reduction (50-70%) in the number of lectin receptors per cell accompanies maturation of proerythroblasts to erythroblasts. Pretreatment of the cells with neuraminidase results in enhanced binding of R. communis agglutinin to proerythroblasts. The number of additional R. communis agglutinin receptors exposed by enzyme treatment remains relatively constant during subsequent cell maturation.", "contents": "Changes in number, mobility, and topographical distribution of lectin receptors during maturation of chick erythroid cells. Plant lectins have been used to probe changes in cell surface characteristics that accompny differentiation in a complete series of chick erythroid cells. Dramatic differences in lectin receptor mobility were observed between the most immature cells of the series, the proerythroblasts, and cells at the next stage of maturation, the erythroblasts. Both concanavalin A and Ricinus communis agglutinin form caps on proerythroblasts, whereas they develop a patchy distribution on erythroblasts. Erythroid cells at later developmental stages show a homogeneous distribution of surface-bound R. communis agglutinin. Concanavalin A also shows a uniform distribution on the cell periphery, but appears to be concentrated in a ring above the perinuclear region of the cell. In addition to changes in mobility of lectin receptors, a large reduction (50-70%) in the number of lectin receptors per cell accompanies maturation of proerythroblasts to erythroblasts. Pretreatment of the cells with neuraminidase results in enhanced binding of R. communis agglutinin to proerythroblasts. The number of additional R. communis agglutinin receptors exposed by enzyme treatment remains relatively constant during subsequent cell maturation."} {"id": "PMID:1270515", "title": "Orderly arrangement of ribosomes in the embryogenic callus tissue of Corylus avellana L.", "content": "Cultured callus tissue of hazel (Corylus avellana L.), which has the potency of somatic embryogenesis, was used for the study of cell ultrastructure in the course of callus growth and embryoid formation. The meristematic cells of this tissue exhibit a specific organization of rough endoplasmic reticulum (RER), stacked into extensive parallel sheets. The membranes of the aggregated RER are associated with orderly arrays of bound ribosomes. The high regularity of the alignment of the attached ribosomes seems to be influenced by the distance between the two neighbouring membranes in the RER aggregate. The RER aggregates with orderly attached ribosomes are more frequently found in callus cells and in early embryogenesis than in the advanced stages of embryo development.", "contents": "Orderly arrangement of ribosomes in the embryogenic callus tissue of Corylus avellana L. Cultured callus tissue of hazel (Corylus avellana L.), which has the potency of somatic embryogenesis, was used for the study of cell ultrastructure in the course of callus growth and embryoid formation. The meristematic cells of this tissue exhibit a specific organization of rough endoplasmic reticulum (RER), stacked into extensive parallel sheets. The membranes of the aggregated RER are associated with orderly arrays of bound ribosomes. The high regularity of the alignment of the attached ribosomes seems to be influenced by the distance between the two neighbouring membranes in the RER aggregate. The RER aggregates with orderly attached ribosomes are more frequently found in callus cells and in early embryogenesis than in the advanced stages of embryo development."} {"id": "PMID:1270516", "title": "Ultrastructural and molecular characteristics of crayfish photoreceptor membranes.", "content": "The ultrastructure of photoreceptor cells of the crayfish (P. clarkii) has been examined by means of thin sections and freeze-fracturing. The study reveals that in the photoreceptor membranes there are particles associated primarily with the A faces of freeze-fracture preparations which have a mean diameter of 80-84 A and a density of 6,600 per per micrometer2. Treatment of the retina with digitonin (a substance capable of extracting visual photopigments) in Ringer's causes marked disruption of the hexagonal arrangement of the microvilli, breakdown of the microvilli into smaller segments, and gradual removal of the particles. The estimated photopigment concentration in the microvillus is 4,000 per micrometer. It is suggested that the observed particles represent the photopigment in situ.", "contents": "Ultrastructural and molecular characteristics of crayfish photoreceptor membranes. The ultrastructure of photoreceptor cells of the crayfish (P. clarkii) has been examined by means of thin sections and freeze-fracturing. The study reveals that in the photoreceptor membranes there are particles associated primarily with the A faces of freeze-fracture preparations which have a mean diameter of 80-84 A and a density of 6,600 per per micrometer2. Treatment of the retina with digitonin (a substance capable of extracting visual photopigments) in Ringer's causes marked disruption of the hexagonal arrangement of the microvilli, breakdown of the microvilli into smaller segments, and gradual removal of the particles. The estimated photopigment concentration in the microvillus is 4,000 per micrometer. It is suggested that the observed particles represent the photopigment in situ."} {"id": "PMID:1270517", "title": "DNA replication in Chinese hamster ovary cells made permeable to nucleotides by tween-80 treatment.", "content": "We have developed a method for permeabilizing CHO cells to nucleotides under conditions which allow most cells to remain viable. Permeabilized cells can carry out ATP-dependent, semiconservative synthesis of DNA. The data are consistent with the continuation of DNA synthesis in those cells in S phase at the time of treatment, possibly limited to completion of replicon synthesis without new initiations.", "contents": "DNA replication in Chinese hamster ovary cells made permeable to nucleotides by tween-80 treatment. We have developed a method for permeabilizing CHO cells to nucleotides under conditions which allow most cells to remain viable. Permeabilized cells can carry out ATP-dependent, semiconservative synthesis of DNA. The data are consistent with the continuation of DNA synthesis in those cells in S phase at the time of treatment, possibly limited to completion of replicon synthesis without new initiations."} {"id": "PMID:1270518", "title": "Steroids and hematopoiesis. I. The effect of steroids on in vitro erythroid colony growth: structure/activity relationships.", "content": "When substituted steroids of several classes are added to cultures of rat bone marrow cells in the presence of erythropoietin a consistent enhancement of the number of colonies of hemoglobin synthesizing cells is obtained. Maximum steroid effectiveness was found to be between 10(-6) and 10(-7) M. Representative compounds of several classes of steroids were examined for their ability to enhance colony growth, including delta 4-estrenes, delta 4-androstenes, 5alpha-H androstanes and estranes, 5beta-H estranes, pregnanes and androstanes. While testosterone and its 5alpha-H derivatives had little or no activity, many synthetic derivatives of testosterone were highly active in increasing erythroid colony growth. All 5beta-H androstanes, estranes, and all but one 5beta-H pregnane were active. Cortisol consistently inhibited colony growth and estradiol and progesterone had no significant effect.", "contents": "Steroids and hematopoiesis. I. The effect of steroids on in vitro erythroid colony growth: structure/activity relationships. When substituted steroids of several classes are added to cultures of rat bone marrow cells in the presence of erythropoietin a consistent enhancement of the number of colonies of hemoglobin synthesizing cells is obtained. Maximum steroid effectiveness was found to be between 10(-6) and 10(-7) M. Representative compounds of several classes of steroids were examined for their ability to enhance colony growth, including delta 4-estrenes, delta 4-androstenes, 5alpha-H androstanes and estranes, 5beta-H estranes, pregnanes and androstanes. While testosterone and its 5alpha-H derivatives had little or no activity, many synthetic derivatives of testosterone were highly active in increasing erythroid colony growth. All 5beta-H androstanes, estranes, and all but one 5beta-H pregnane were active. Cortisol consistently inhibited colony growth and estradiol and progesterone had no significant effect."} {"id": "PMID:1270519", "title": "Electrical properties of developing oocytes of the migratory locust, Locusta migratoria.", "content": "The electrical properties of developing nonfertilized oocytes of Locusta migratoria were studied, using intracellular microelectrodes. The inseries potential of the combined oomembrane and of the follicular cells was about 20 mV in the youngest oocytes. It increased as the oocytes developed and it reached a plateau of about 50 mV before full maturation, generally four to seven oocytes away from the fully-developed terminal oocyte. Current-voltage relations were always linear for hyperpolarizing currents. Most oocytes exhibited, however, rectification to outward current. Input resistance values varied with oocyte size from about 5 X 10(6) ohm for young oocytes to about 0.2 X 10(6) ohm for the more developed ones. Some oocytes displayed a transient depolarization on turning off a hyperpolarizing step of current. This depolarization was not correlated with the size of the oocyte or with any observed morphological feature. Any two adjacent oocytes were electrotonically coupled. A single ovariole thus represented a longitudinal chain of developing oocytes which were connected electrically. This was supported by electron microscope observations which revealed junctions partially impermeable to lanthanum and gap junctions between the follicular cells themselves and between follicular cells and oocytes. The coupling coefficient was dependent on the direction of current flow. The attenuation of voltage along an ovariole was always greater at the distal than at the proximal side.", "contents": "Electrical properties of developing oocytes of the migratory locust, Locusta migratoria. The electrical properties of developing nonfertilized oocytes of Locusta migratoria were studied, using intracellular microelectrodes. The inseries potential of the combined oomembrane and of the follicular cells was about 20 mV in the youngest oocytes. It increased as the oocytes developed and it reached a plateau of about 50 mV before full maturation, generally four to seven oocytes away from the fully-developed terminal oocyte. Current-voltage relations were always linear for hyperpolarizing currents. Most oocytes exhibited, however, rectification to outward current. Input resistance values varied with oocyte size from about 5 X 10(6) ohm for young oocytes to about 0.2 X 10(6) ohm for the more developed ones. Some oocytes displayed a transient depolarization on turning off a hyperpolarizing step of current. This depolarization was not correlated with the size of the oocyte or with any observed morphological feature. Any two adjacent oocytes were electrotonically coupled. A single ovariole thus represented a longitudinal chain of developing oocytes which were connected electrically. This was supported by electron microscope observations which revealed junctions partially impermeable to lanthanum and gap junctions between the follicular cells themselves and between follicular cells and oocytes. The coupling coefficient was dependent on the direction of current flow. The attenuation of voltage along an ovariole was always greater at the distal than at the proximal side."} {"id": "PMID:1270520", "title": "Interrelationships between water and cellular metabolism in Artemia cysts. IV. Adenosine 5'-triphosphate and cyst hydration.", "content": "The concentration of ATP in cysts of the brine shrimp, Artemia salina, has been studied as a function of cyst hydration. Cysts dried over CaSO4 contain 0.02 gH2O/g cysts and 0.54 +/- 0.05 (S.D.) mumoles of ATP/g dried cysts. Addition of water up to 0.05 g/g cysts produced no net change in the level of ATP during incubation. Hydration levels between 0.05 and 0.62 g/g cysts resulted in a net loss of ATP, whereas above 0.65 g/g cysts a net increase was observed with incubation time. No net change in the amount of ATP, compared with dried cysts, was detected between the latter two hydrations. These results, when integrated with those from previous work, indicate that conventional aerobic energy metabolism does not begin until cyst hydrations of about 0.65 g/g are achieved. The fate of ATP in cysts hydrated to levels lower than 0.65 g/g was discussed.", "contents": "Interrelationships between water and cellular metabolism in Artemia cysts. IV. Adenosine 5'-triphosphate and cyst hydration. The concentration of ATP in cysts of the brine shrimp, Artemia salina, has been studied as a function of cyst hydration. Cysts dried over CaSO4 contain 0.02 gH2O/g cysts and 0.54 +/- 0.05 (S.D.) mumoles of ATP/g dried cysts. Addition of water up to 0.05 g/g cysts produced no net change in the level of ATP during incubation. Hydration levels between 0.05 and 0.62 g/g cysts resulted in a net loss of ATP, whereas above 0.65 g/g cysts a net increase was observed with incubation time. No net change in the amount of ATP, compared with dried cysts, was detected between the latter two hydrations. These results, when integrated with those from previous work, indicate that conventional aerobic energy metabolism does not begin until cyst hydrations of about 0.65 g/g are achieved. The fate of ATP in cysts hydrated to levels lower than 0.65 g/g was discussed."} {"id": "PMID:1270521", "title": "The transport of chloride in Ehrlich ascites tumor cells.", "content": "The steady state transport and distribution of chloride between the intracellular and extracellular phases was investigated when the extracellular chloride concentration was varied by isosmotic replacement with nitrate, bromide and acetate. The results of these experiments show that chloride transport, measured by uptake of 36Cl, is sensitive to the replacement anion. In the presence of nitrate, chloride transport is a linear function of the extracellular chloride concentration. The relationship between chloride transport and extracellular chloride in the presence of bromide is concave upward which suggests that this anion inhibits chloride movement. However, when acetate replaces chloride, the relationship between chloride transport and extracellular chloride is concave downward. The chloride distribution ratio of cells incubated in 145-155mM chloride medium is 0.386 and is not effected by the replacement of chloride with nitrate, bromide or acetate. These findings are consistent with the assertion that chloride transport is composed of two parallel pathways, a diffusional plus a saturating, mediated component. Of the total chloride flux (9.1 mmoles Cl-/kg dry weight per minute) measured in chloride medium (145-155 mM Cl-), the mediated component represents 40% and the diffusional component 60%.", "contents": "The transport of chloride in Ehrlich ascites tumor cells. The steady state transport and distribution of chloride between the intracellular and extracellular phases was investigated when the extracellular chloride concentration was varied by isosmotic replacement with nitrate, bromide and acetate. The results of these experiments show that chloride transport, measured by uptake of 36Cl, is sensitive to the replacement anion. In the presence of nitrate, chloride transport is a linear function of the extracellular chloride concentration. The relationship between chloride transport and extracellular chloride in the presence of bromide is concave upward which suggests that this anion inhibits chloride movement. However, when acetate replaces chloride, the relationship between chloride transport and extracellular chloride is concave downward. The chloride distribution ratio of cells incubated in 145-155mM chloride medium is 0.386 and is not effected by the replacement of chloride with nitrate, bromide or acetate. These findings are consistent with the assertion that chloride transport is composed of two parallel pathways, a diffusional plus a saturating, mediated component. Of the total chloride flux (9.1 mmoles Cl-/kg dry weight per minute) measured in chloride medium (145-155 mM Cl-), the mediated component represents 40% and the diffusional component 60%."} {"id": "PMID:1270522", "title": "Wasting of 18 S ribosomal RNA by human myeloma cells cultured in adenosine.", "content": "When human myeloma cells are pulsed for one hour with 3H-uridine and chased for six hours in fresh medium containing unlabeled uridine, the processing of 45 S rRNA precursor into the stable 28 S and 18 S rRNA components can be followed. However, when the cells are chased in exogenous adenosine instead of uridine, the accumulation of 18 S rRNA is selectively inhibited. Cells pulsed with 3H-adenosine and chased in the absence of exogenous nucleosides exhibit normal rRNA precursor processing, while cells pulsed simultaneously with 3H-uridine and 3H-adenosine and chased with uridine and adenosine are deficient in labeled 18 S rRNA. Consequently, the inhibition of 18 S rRNA accumulation by adenosine is not an artifact of labeling nor is it relieved by an equal molar concentration of uridine. The wasting of 18 S rRNA in human myeloma cells is similar to that reported to occur in normal lymphocytes during the quiescent state.", "contents": "Wasting of 18 S ribosomal RNA by human myeloma cells cultured in adenosine. When human myeloma cells are pulsed for one hour with 3H-uridine and chased for six hours in fresh medium containing unlabeled uridine, the processing of 45 S rRNA precursor into the stable 28 S and 18 S rRNA components can be followed. However, when the cells are chased in exogenous adenosine instead of uridine, the accumulation of 18 S rRNA is selectively inhibited. Cells pulsed with 3H-adenosine and chased in the absence of exogenous nucleosides exhibit normal rRNA precursor processing, while cells pulsed simultaneously with 3H-uridine and 3H-adenosine and chased with uridine and adenosine are deficient in labeled 18 S rRNA. Consequently, the inhibition of 18 S rRNA accumulation by adenosine is not an artifact of labeling nor is it relieved by an equal molar concentration of uridine. The wasting of 18 S rRNA in human myeloma cells is similar to that reported to occur in normal lymphocytes during the quiescent state."} {"id": "PMID:1270523", "title": "Surface interactions between mammalian sperm and egg: variation of spermatozoa concentration as a probe for the study of binding in vitro.", "content": "The pre-penetration binding interactions between gametes of the golden hamster were investigated in vitro. Binding between capacitated spermatozoa and the surface of eggs, that is the zonae pellucidae with intact vitelli, as a function of the concentration of spermatozoa, followed a sigmoidal curve. This was in sharp contrast to the linear binding obtained with mechanically isolated zonae pellucidae (zonae lacking vitelli). Penetration of eggs as a function of the concentration of spermatozoa paralleled the binding curve that occurred between gametes. The binding curve obtained with uncapacitated spermatozoa and eggs was not sigmoidal but was linear after a slight lag and parallel to the curve obtained with uncapacitated spermatozoa and isolated zonae pellucidae. Taken together these results support previous work which implicated a vitelline factor in the binding reaction between the surfaces of eggs and capacitated spermatozoa. By scoring binding at one minute intervals it was possible to relate the rapid uninterrupted binding that occurs between capacitated spermatozoa and isolated zonae pellucidae with the equally rapid but transient and vitellus-influenced binding that occurs between gametes. It was concluded that the vitelline factor acts by preventing most of the early type of binding that occurs between spermatozoa and isolated zonae pellucidae and not by terminating the early, rapid, initial binding as previously postulated. Thus, this early binding never occurs between most of the gametes that finally bind 30 to 40 minutes later and, therefore, does not play a role in the establishment of the late binding step which leads to penetration.", "contents": "Surface interactions between mammalian sperm and egg: variation of spermatozoa concentration as a probe for the study of binding in vitro. The pre-penetration binding interactions between gametes of the golden hamster were investigated in vitro. Binding between capacitated spermatozoa and the surface of eggs, that is the zonae pellucidae with intact vitelli, as a function of the concentration of spermatozoa, followed a sigmoidal curve. This was in sharp contrast to the linear binding obtained with mechanically isolated zonae pellucidae (zonae lacking vitelli). Penetration of eggs as a function of the concentration of spermatozoa paralleled the binding curve that occurred between gametes. The binding curve obtained with uncapacitated spermatozoa and eggs was not sigmoidal but was linear after a slight lag and parallel to the curve obtained with uncapacitated spermatozoa and isolated zonae pellucidae. Taken together these results support previous work which implicated a vitelline factor in the binding reaction between the surfaces of eggs and capacitated spermatozoa. By scoring binding at one minute intervals it was possible to relate the rapid uninterrupted binding that occurs between capacitated spermatozoa and isolated zonae pellucidae with the equally rapid but transient and vitellus-influenced binding that occurs between gametes. It was concluded that the vitelline factor acts by preventing most of the early type of binding that occurs between spermatozoa and isolated zonae pellucidae and not by terminating the early, rapid, initial binding as previously postulated. Thus, this early binding never occurs between most of the gametes that finally bind 30 to 40 minutes later and, therefore, does not play a role in the establishment of the late binding step which leads to penetration."} {"id": "PMID:1270525", "title": "Effect of serum on the growth of Balb oT3 A31 mouse fibroblasts and an SV40-transformed derivative.", "content": "The effect of serum on the growth properties of non-transformed Balb 3T3 A31 and SV40-transformed Balb 3T3 A31 was studied. The concentration of serum in the growth medium of non-transformed cells had little effect on the initial population doubling time, but did regulate the cell density at which the population became quiescent in G1. The doubling time of transformed cells, however, was increased significantly as the concentration of serum was decreased below 4%. This effect on the growth of transformed cells was seen at serum concentrations so low that non-transformed cells did not complete one population doubling. Flow microfluorometric analysis of these populations indicated that the primary effect of different serum concentrations on the non-transformed cells was to modulate the average residence time in G1, whereas, all the cell cycle phases of the transformed cells were affected by serum. At saturation densities, the non-transformed cells became quiescent in G1, but the transformed cells still traversed the cell cycle and their saturation density appeared to be a balance between cell production and cell death occurring primarily in the G1 phase of the cell cycle.", "contents": "Effect of serum on the growth of Balb oT3 A31 mouse fibroblasts and an SV40-transformed derivative. The effect of serum on the growth properties of non-transformed Balb 3T3 A31 and SV40-transformed Balb 3T3 A31 was studied. The concentration of serum in the growth medium of non-transformed cells had little effect on the initial population doubling time, but did regulate the cell density at which the population became quiescent in G1. The doubling time of transformed cells, however, was increased significantly as the concentration of serum was decreased below 4%. This effect on the growth of transformed cells was seen at serum concentrations so low that non-transformed cells did not complete one population doubling. Flow microfluorometric analysis of these populations indicated that the primary effect of different serum concentrations on the non-transformed cells was to modulate the average residence time in G1, whereas, all the cell cycle phases of the transformed cells were affected by serum. At saturation densities, the non-transformed cells became quiescent in G1, but the transformed cells still traversed the cell cycle and their saturation density appeared to be a balance between cell production and cell death occurring primarily in the G1 phase of the cell cycle."} {"id": "PMID:1270526", "title": "Carbohydrate preferences of mammalian cells.", "content": "Carbohydrate preferences of mammalian cells can be utilized to biochemically distinguish between different cell lines. Ninety-three carbohydrates were examined of which (a) 15 supported cell proliferation and (b) 42 were toxic or growth inhibitory. The present investigation has employed an enzymatic system to eliminate trace glucose levels from reagents and glucose generated by serum enzymes.", "contents": "Carbohydrate preferences of mammalian cells. Carbohydrate preferences of mammalian cells can be utilized to biochemically distinguish between different cell lines. Ninety-three carbohydrates were examined of which (a) 15 supported cell proliferation and (b) 42 were toxic or growth inhibitory. The present investigation has employed an enzymatic system to eliminate trace glucose levels from reagents and glucose generated by serum enzymes."} {"id": "PMID:1270527", "title": "Degradation of abnormal proteins in HeLa cells.", "content": "Canavanine, an arginine analog, is incorporated into HeLa cell protein when cells are incubated in the absence of arginine, and this incorporation can result in the production of nonfunctional enzymes or abnormal proteins. The cells degrade these abnormal proteins up to three times more rapidly than normal cell proteins. The capacity for selective degradation of abnormal proteins is not limited to HeLa cells since human fibroblasts also showed increased degradative rates following exposure to canavanine. In addition, enhanced degradation is not a peculiar property of canavanine incorporation since other amino acid analogs also promoted protein degradation. Thus, mammalian cells have the capacity to recognize and selectively degrade abnormal proteins.", "contents": "Degradation of abnormal proteins in HeLa cells. Canavanine, an arginine analog, is incorporated into HeLa cell protein when cells are incubated in the absence of arginine, and this incorporation can result in the production of nonfunctional enzymes or abnormal proteins. The cells degrade these abnormal proteins up to three times more rapidly than normal cell proteins. The capacity for selective degradation of abnormal proteins is not limited to HeLa cells since human fibroblasts also showed increased degradative rates following exposure to canavanine. In addition, enhanced degradation is not a peculiar property of canavanine incorporation since other amino acid analogs also promoted protein degradation. Thus, mammalian cells have the capacity to recognize and selectively degrade abnormal proteins."} {"id": "PMID:1270528", "title": "Inhibition of cell division in amoebae: the incorporation of tritiated precursors into Amoeba proteus after the injection of non-homologous cytoplasm.", "content": "The injection of non-homologous cytoplasm into any strain of large free-living amoebae leads to a 60% inhibition of division amongst recipient cells. When the post-microsomal supernatant fraction of Amoeba discoides was injected into A. proteus, this inhibition of division was as high as 95%. The incorporation of tritiated precursors, either [3H]uridine or 3H-amino acids, into these inhibited amoebae was studied at various times after the injection of the inhibitory material using autoradiography. When cells were grown in [3H]uridine, autoradiographs indicated that RNA synthesis had ceased 2 days after the injection of non-homologous material. However, if [3H]uridine was injected into the inhibited cells, some synthesis of RNA could be detected up to 4 days after the injection of inhibitor. These results suggested that uptake of [3H]uridine was impaired and that one site of action of the inhibitory molecules was RNA synthesis for membrane components. Experiments with a variety of 3H-amino acids suggested that protein synthesis continued for at least 9 days after the injection of non-homologous cytoplasm, and that in these cells some informational RNA molecules were long-lived. There seemed to be accumulation of material containing [3H]lysine in the nuclei of control cells taken at random from cultures, and this was seen in the nuclei of inhibited cells 1 day after injection. However, 2 days after the injection of inhibitor, no accumulation of [3H]lysine-containing material was found in the nuclei.", "contents": "Inhibition of cell division in amoebae: the incorporation of tritiated precursors into Amoeba proteus after the injection of non-homologous cytoplasm. The injection of non-homologous cytoplasm into any strain of large free-living amoebae leads to a 60% inhibition of division amongst recipient cells. When the post-microsomal supernatant fraction of Amoeba discoides was injected into A. proteus, this inhibition of division was as high as 95%. The incorporation of tritiated precursors, either [3H]uridine or 3H-amino acids, into these inhibited amoebae was studied at various times after the injection of the inhibitory material using autoradiography. When cells were grown in [3H]uridine, autoradiographs indicated that RNA synthesis had ceased 2 days after the injection of non-homologous material. However, if [3H]uridine was injected into the inhibited cells, some synthesis of RNA could be detected up to 4 days after the injection of inhibitor. These results suggested that uptake of [3H]uridine was impaired and that one site of action of the inhibitory molecules was RNA synthesis for membrane components. Experiments with a variety of 3H-amino acids suggested that protein synthesis continued for at least 9 days after the injection of non-homologous cytoplasm, and that in these cells some informational RNA molecules were long-lived. There seemed to be accumulation of material containing [3H]lysine in the nuclei of control cells taken at random from cultures, and this was seen in the nuclei of inhibited cells 1 day after injection. However, 2 days after the injection of inhibitor, no accumulation of [3H]lysine-containing material was found in the nuclei."} {"id": "PMID:1270529", "title": "The cell cycle during amphibian limb regeneration.", "content": "The duration of the cell cycle in the blastema of regenerating limbs of axolotls has been measured by means of [3H]thymidine pulse labelling and autoradiography. A chase was required to define the pulse period. An average cell cycle at 20 degrees C takes 53 h, S-phase takes 38 h; including parts of mitosis, G1 is 10 h and G2 is 5 h long. The protracted cycle and S-phase are consonant with the large genome in axolotis and other urodeles. The rapidly growing blastema probably contains a steady population of about 5000 proliferating cells, as there is a regular withdrawal of differentiating cells from the population. The kinds of determination which exist in this population of cells, or are exerted on it, are briefly considered.", "contents": "The cell cycle during amphibian limb regeneration. The duration of the cell cycle in the blastema of regenerating limbs of axolotls has been measured by means of [3H]thymidine pulse labelling and autoradiography. A chase was required to define the pulse period. An average cell cycle at 20 degrees C takes 53 h, S-phase takes 38 h; including parts of mitosis, G1 is 10 h and G2 is 5 h long. The protracted cycle and S-phase are consonant with the large genome in axolotis and other urodeles. The rapidly growing blastema probably contains a steady population of about 5000 proliferating cells, as there is a regular withdrawal of differentiating cells from the population. The kinds of determination which exist in this population of cells, or are exerted on it, are briefly considered."} {"id": "PMID:1270530", "title": "Meiotic maturation of mouse oocytes in vitro: association of newly synthesized proteins with condensing chromosomes.", "content": "The nature, intracellular distribution, and role of proteins synthesized during meiotic maturation of mouse oocytes in vitro have been examined. Proteins synthesized during the initial stages of maturation are concentrated within the nucleus (germinal vesicle) and become intimately associated with the condensing chromosomes. Inhibition of protein synthesis during this period does not prevent germinal vesicle dissolution or chromosome condensation, but meiotic progression is blocked reversibly at the circular bivalent stage. A protein is synthesized during meiotic maturation of the mouse oocyte which exhibits several of the characteristics of the very lysine-rich histone, FI; this and other histones are phosphorylated during the initial stages of maturation. These results are discussed in relation to studies of meiotic maturation of oocytes from non-mammalian species and chromosome condensation in both oocytes and mitotic cells.", "contents": "Meiotic maturation of mouse oocytes in vitro: association of newly synthesized proteins with condensing chromosomes. The nature, intracellular distribution, and role of proteins synthesized during meiotic maturation of mouse oocytes in vitro have been examined. Proteins synthesized during the initial stages of maturation are concentrated within the nucleus (germinal vesicle) and become intimately associated with the condensing chromosomes. Inhibition of protein synthesis during this period does not prevent germinal vesicle dissolution or chromosome condensation, but meiotic progression is blocked reversibly at the circular bivalent stage. A protein is synthesized during meiotic maturation of the mouse oocyte which exhibits several of the characteristics of the very lysine-rich histone, FI; this and other histones are phosphorylated during the initial stages of maturation. These results are discussed in relation to studies of meiotic maturation of oocytes from non-mammalian species and chromosome condensation in both oocytes and mitotic cells."} {"id": "PMID:1270531", "title": "Similarities between platelet contraction and cellular motility during mitosis: role of platelet microtubules in clot retraction.", "content": "The effects of inhibitors of mitosis, energy metabolism and protein synthesis on clot retraction were investigated. The results show that (1) Incubation of colchicine (0-01-0-1 mM) with platelet-rich plasma (PRP) inhibits the subsequent retraction of clots derived from diluted PRP. (2) Inhibition of clot retraction by high concentrations of colchicine (up to 40 mM) can be overcome by increasing the platelet concentration in the system. (3) Incubation of clots in colchicine or 80% D2O solutions inhibits their retraction. Exposure of partially retracted clots to these agents is without effect. (4) Hydrostatic pressure retards clot retraction. (5) Incubation of PRP with either 2-deoxy-D-glucose or antimycin alone does not affect clot retraction, but a combination of these agents is inhibitory. (6) Clot retraction is not inhibited by puromycin or cycloheximide. (7) Platelets in retracting clots have constricted regions containing microfilaments and pseudopods containing microtubules. Fibrin strands are progressively condensed around the constricted regions as retraction advances. (8) The development of platelet constriction, platelet pseudopods and the intracellular microfilaments are delayed in colchicinized clots, corresponding to the retardation of retraction. Following the initial delay of retraction colchicinized clots, like controls, show condensation of fibrin strands adjacent to these constricted areas of platelets containing microfilaments. The formation of pseudopods is impaired and no microtubules are found in platelets in the presence of colchicine. The above results suggest that the thrombin-induced platelet contraction during clot retraction is a coordinated movement, which, under optimal conditions involves both microtubules and microfilaments. The contraction of microfilaments produces the constriction of platelets and brings about clot retraction by reducing the angle between fibrin strands. Platelet microtubules are related to the development of pseudopods and play a supplementary role in facilitating microfilament-mediated cellular constriction. The similarities between platelet contraction and cellular motility in mitosis is discussed.", "contents": "Similarities between platelet contraction and cellular motility during mitosis: role of platelet microtubules in clot retraction. The effects of inhibitors of mitosis, energy metabolism and protein synthesis on clot retraction were investigated. The results show that (1) Incubation of colchicine (0-01-0-1 mM) with platelet-rich plasma (PRP) inhibits the subsequent retraction of clots derived from diluted PRP. (2) Inhibition of clot retraction by high concentrations of colchicine (up to 40 mM) can be overcome by increasing the platelet concentration in the system. (3) Incubation of clots in colchicine or 80% D2O solutions inhibits their retraction. Exposure of partially retracted clots to these agents is without effect. (4) Hydrostatic pressure retards clot retraction. (5) Incubation of PRP with either 2-deoxy-D-glucose or antimycin alone does not affect clot retraction, but a combination of these agents is inhibitory. (6) Clot retraction is not inhibited by puromycin or cycloheximide. (7) Platelets in retracting clots have constricted regions containing microfilaments and pseudopods containing microtubules. Fibrin strands are progressively condensed around the constricted regions as retraction advances. (8) The development of platelet constriction, platelet pseudopods and the intracellular microfilaments are delayed in colchicinized clots, corresponding to the retardation of retraction. Following the initial delay of retraction colchicinized clots, like controls, show condensation of fibrin strands adjacent to these constricted areas of platelets containing microfilaments. The formation of pseudopods is impaired and no microtubules are found in platelets in the presence of colchicine. The above results suggest that the thrombin-induced platelet contraction during clot retraction is a coordinated movement, which, under optimal conditions involves both microtubules and microfilaments. The contraction of microfilaments produces the constriction of platelets and brings about clot retraction by reducing the angle between fibrin strands. Platelet microtubules are related to the development of pseudopods and play a supplementary role in facilitating microfilament-mediated cellular constriction. The similarities between platelet contraction and cellular motility in mitosis is discussed."} {"id": "PMID:1270532", "title": "Rotary movements and fluid membranes in termite flagellates.", "content": "We previously described a remarkable type of cell motility that provided direct, visual evidence for the fluid nature of cell membranes. The movement involved continual, unidirectional rotation of one part of a protozoan, including the plasma membrane and cytoplasmic organelles, in relation to a neighbouring part. The cell membrane in the 'shear zone' appeared continuous with that of the rest of the cell. The rotary motor consisted, at least in part, of a non-contractile, microtubular axostyle which extended centrally through the cell. The protozoan was a devescovinid flagellate found in the hindgut of a Florida termite. In this paper, we have confirmed earlier reports of this type of motility in other kinds of devescovinids from Australian termites. By demonstrating continuity of the plasma membrane in the shear zone of the Australian devescovinids as well, we have obtained additional examples that provide direct, visual evidence for fluid membranes. A comparative analysis of rotational motility in various devescovinids revealed 2 different kinds of rotary mechanisms. Hyperdevescovina probably have an internal motor, in which one part of the cell exerts forces against another part, as in the Florida termite devescovinid. Devescovina species, on the other hand, have an external motor, in which flagellar and/or papillar movements exert forces against the surrounding medium. The structure of the axostyle in different devescovinids was compared, and its role in rotational motility discussed with respect to the behavioural data.", "contents": "Rotary movements and fluid membranes in termite flagellates. We previously described a remarkable type of cell motility that provided direct, visual evidence for the fluid nature of cell membranes. The movement involved continual, unidirectional rotation of one part of a protozoan, including the plasma membrane and cytoplasmic organelles, in relation to a neighbouring part. The cell membrane in the 'shear zone' appeared continuous with that of the rest of the cell. The rotary motor consisted, at least in part, of a non-contractile, microtubular axostyle which extended centrally through the cell. The protozoan was a devescovinid flagellate found in the hindgut of a Florida termite. In this paper, we have confirmed earlier reports of this type of motility in other kinds of devescovinids from Australian termites. By demonstrating continuity of the plasma membrane in the shear zone of the Australian devescovinids as well, we have obtained additional examples that provide direct, visual evidence for fluid membranes. A comparative analysis of rotational motility in various devescovinids revealed 2 different kinds of rotary mechanisms. Hyperdevescovina probably have an internal motor, in which one part of the cell exerts forces against another part, as in the Florida termite devescovinid. Devescovina species, on the other hand, have an external motor, in which flagellar and/or papillar movements exert forces against the surrounding medium. The structure of the axostyle in different devescovinids was compared, and its role in rotational motility discussed with respect to the behavioural data."} {"id": "PMID:1270533", "title": "Flagellar regeneration in Chlamydomonas reinhardtii: evidence that cycloheximide pulses induce a delay in morphogenesis.", "content": "The behaviour of a pool of flagellar precursors, assayed by the ability of cells to regenerate flagella in the absence of de novo protein synthesis, has been examined during organelle morphogenesis in the biflagellate alga Chlamydomonas. The results demonstrate that flagellar elongation can continue even when this pool is apparently empty and suggest that 2 sources of precursors are available to the regenerating flagella: those pre-existing in the cellular pool and those synthesized de novo. Further evidence for this was obtained by subjecting regenerating cells to pulses of cycloheximide. Cells exposed to this drug during the first 60 min post deflagellation formed only half-length (5-mum) flagella, whereas a pulse administered after this point allowed the formation of longer flagella and suggested that some de novo protein synthesis was required for the formation of full-length flagella, although it was not a prerequisite for the initiation of regeneration. In addition, it was found that, subsequent to the removal of the cycloheximide, flagellar regeneration did not recommence immediately, but was delayed for a period of approximately 45 min, irrespective of length of flagella formed prior to drug inhibition. The nature of this cycloheximide-induced delay is unclear and certain alternatives, based on the exhaustion of structural/regulatory components are considered. Although it is not possible to distinguish between these alternatives, tubulin is not the limiting component, since a pool of this protein is present when flagellar elongation is prevented by cycloheximide.", "contents": "Flagellar regeneration in Chlamydomonas reinhardtii: evidence that cycloheximide pulses induce a delay in morphogenesis. The behaviour of a pool of flagellar precursors, assayed by the ability of cells to regenerate flagella in the absence of de novo protein synthesis, has been examined during organelle morphogenesis in the biflagellate alga Chlamydomonas. The results demonstrate that flagellar elongation can continue even when this pool is apparently empty and suggest that 2 sources of precursors are available to the regenerating flagella: those pre-existing in the cellular pool and those synthesized de novo. Further evidence for this was obtained by subjecting regenerating cells to pulses of cycloheximide. Cells exposed to this drug during the first 60 min post deflagellation formed only half-length (5-mum) flagella, whereas a pulse administered after this point allowed the formation of longer flagella and suggested that some de novo protein synthesis was required for the formation of full-length flagella, although it was not a prerequisite for the initiation of regeneration. In addition, it was found that, subsequent to the removal of the cycloheximide, flagellar regeneration did not recommence immediately, but was delayed for a period of approximately 45 min, irrespective of length of flagella formed prior to drug inhibition. The nature of this cycloheximide-induced delay is unclear and certain alternatives, based on the exhaustion of structural/regulatory components are considered. Although it is not possible to distinguish between these alternatives, tubulin is not the limiting component, since a pool of this protein is present when flagellar elongation is prevented by cycloheximide."} {"id": "PMID:1270534", "title": "Developmental mechanisms in heterospory. III. The plastid cycle during megasporogenesis in Isoetes.", "content": "The megasporocyte of Isoetes englemanni at the leptotene-zygotene interval of meiosis contains 4 disk-shaped proplastids about 12 mum in diameter. The disposition of these organelles in the cell is such that each of the four megaspores delimited during cytokinesis contains a single proplastid. During prophase and following their incorporation into the spores, the proplastids are undergoing fission by budding. The buds are first discernible as low surface evaginations which contain a complement of granular somal material, some wefts of tubular membrane and osmiophilic globuli, in addition to a number of vesicles derived by invagination from the inner membrane of the proplastid envelope. As the evaginations emerge they enlarge and the link with the parent body is reduced to a narrow channel. At this stage one or more of the vesicles derived from the proplastid envelope comes into register with the lumen of the channel. One vesicle is transported into the lumen, elongating as it passes through. The passage of the vesicle into the channel destroys the connexion between the matrix of the evagination and the stroma of the proplastid. The occurrence in the cytoplasm around the proplastid of bodies not connected to the proplastid, but identical in structure to the evaginations and carrying a membranous tail suggests that the evaginations are released by abscission of the channel close to the surface of the parent body. After release the bodies undergo division by constriction. Regression of the tail follows division in those bodies which are regular in outline and in which the matrix is ultrastructurally similar to the stroma of the parent organelle. The process does not seem to occur in co-existing forms which have assumed an irregular outline and have a less-opque matrix. The more mature megaspore of Isoetes contains proplastids up to 4 mum in greatest dimension. The stroma in these is dense and granular and contains membrane-bound vesicles, osmiophilic globuli, starch granules and wefts of tubular membrane. There is no evidence that the large budding organelle persists to this later stage in development. The resemblance of the plastids in the more mature megaspore to the bodies produced by evagination earlier in development suggests a common identity. The observations and interpretations lead to the proposition that the plastids in Isoetes englemanni are autonomous. This situation contrasts with the one described for another heterosporous haploid dioecious pteridophyte, Marsilea vestita, where nucleocytoplasmic interaction has been interpreted as the de novo creation of plastids and mitochondria following the elimination by autophagy of the organelles inherited at meiosis. It is suggested that an explanation to account for the 2 different mechanisms might be sought in regard to the degree of developmental success enjoyed by the individual megaspores in the 2 plants. In Isoetes all 4 megaspores of every tetrad survive and develop, while in Marsilea the mature megasporangium contains a single functional megaspore.", "contents": "Developmental mechanisms in heterospory. III. The plastid cycle during megasporogenesis in Isoetes. The megasporocyte of Isoetes englemanni at the leptotene-zygotene interval of meiosis contains 4 disk-shaped proplastids about 12 mum in diameter. The disposition of these organelles in the cell is such that each of the four megaspores delimited during cytokinesis contains a single proplastid. During prophase and following their incorporation into the spores, the proplastids are undergoing fission by budding. The buds are first discernible as low surface evaginations which contain a complement of granular somal material, some wefts of tubular membrane and osmiophilic globuli, in addition to a number of vesicles derived by invagination from the inner membrane of the proplastid envelope. As the evaginations emerge they enlarge and the link with the parent body is reduced to a narrow channel. At this stage one or more of the vesicles derived from the proplastid envelope comes into register with the lumen of the channel. One vesicle is transported into the lumen, elongating as it passes through. The passage of the vesicle into the channel destroys the connexion between the matrix of the evagination and the stroma of the proplastid. The occurrence in the cytoplasm around the proplastid of bodies not connected to the proplastid, but identical in structure to the evaginations and carrying a membranous tail suggests that the evaginations are released by abscission of the channel close to the surface of the parent body. After release the bodies undergo division by constriction. Regression of the tail follows division in those bodies which are regular in outline and in which the matrix is ultrastructurally similar to the stroma of the parent organelle. The process does not seem to occur in co-existing forms which have assumed an irregular outline and have a less-opque matrix. The more mature megaspore of Isoetes contains proplastids up to 4 mum in greatest dimension. The stroma in these is dense and granular and contains membrane-bound vesicles, osmiophilic globuli, starch granules and wefts of tubular membrane. There is no evidence that the large budding organelle persists to this later stage in development. The resemblance of the plastids in the more mature megaspore to the bodies produced by evagination earlier in development suggests a common identity. The observations and interpretations lead to the proposition that the plastids in Isoetes englemanni are autonomous. This situation contrasts with the one described for another heterosporous haploid dioecious pteridophyte, Marsilea vestita, where nucleocytoplasmic interaction has been interpreted as the de novo creation of plastids and mitochondria following the elimination by autophagy of the organelles inherited at meiosis. It is suggested that an explanation to account for the 2 different mechanisms might be sought in regard to the degree of developmental success enjoyed by the individual megaspores in the 2 plants. In Isoetes all 4 megaspores of every tetrad survive and develop, while in Marsilea the mature megasporangium contains a single functional megaspore."} {"id": "PMID:1270535", "title": "Brittle fracture of epidermal cells by liquid shear.", "content": "A suspension of epidermal cells obtained from pig tail skin by trypsinization was subjected to high liquid-shear forces in a French press. The material issuing from the press was examined by phase-contrast microscopy, transmission electron microscopy and scanning electron microscopy. The cytoskeleton of tonofibrils retained the shape of cell fragments, and subcellular organelles remained enmeshed in the network of tonofibrils. Examination of some cell fragments by scanning electron microscopy revealed the internal organization of the tonofibrils. The relevance of these findings to the problem of isolating subcellular fractions from epidermis is discussed.", "contents": "Brittle fracture of epidermal cells by liquid shear. A suspension of epidermal cells obtained from pig tail skin by trypsinization was subjected to high liquid-shear forces in a French press. The material issuing from the press was examined by phase-contrast microscopy, transmission electron microscopy and scanning electron microscopy. The cytoskeleton of tonofibrils retained the shape of cell fragments, and subcellular organelles remained enmeshed in the network of tonofibrils. Examination of some cell fragments by scanning electron microscopy revealed the internal organization of the tonofibrils. The relevance of these findings to the problem of isolating subcellular fractions from epidermis is discussed."} {"id": "PMID:1270539", "title": "On-line information systems in perspective.", "content": "The rationale supporting the desirability of on-line information systems and the arguments underlying their development are discussed. A major argument in favor of on-line retrieval has been the assumption that the opportunity to negotiate search problems through on-line access to the data base has the inherent effect of improved system performance. The extent to which on-line retrieval has fulfilled this and other expectations is considered along with trends relating to the operational characteristics of existing systems.", "contents": "On-line information systems in perspective. The rationale supporting the desirability of on-line information systems and the arguments underlying their development are discussed. A major argument in favor of on-line retrieval has been the assumption that the opportunity to negotiate search problems through on-line access to the data base has the inherent effect of improved system performance. The extent to which on-line retrieval has fulfilled this and other expectations is considered along with trends relating to the operational characteristics of existing systems."} {"id": "PMID:1270540", "title": "Selection of descriptors according to discrimination and redundancy. Application to chemical structure searching.", "content": "Descriptors, for our purposes, will be fragment screens in a chemical search system. Given a file of compounds, the discrimination of a set of descriptors can be defined in terms of their incidence and mutual incidence in the file. A theory is developed which provides both a heuristic for selecting descriptors and a method for evaluating their marginal discrimination. These ideas have been used to generate an efficient screen code for a large file of chemical structures.", "contents": "Selection of descriptors according to discrimination and redundancy. Application to chemical structure searching. Descriptors, for our purposes, will be fragment screens in a chemical search system. Given a file of compounds, the discrimination of a set of descriptors can be defined in terms of their incidence and mutual incidence in the file. A theory is developed which provides both a heuristic for selecting descriptors and a method for evaluating their marginal discrimination. These ideas have been used to generate an efficient screen code for a large file of chemical structures."} {"id": "PMID:1270541", "title": "Gas-liquid chromatographic analysis of protein amino acids as N-isobutyloxycarbonylamino acid methyl esters.", "content": "A practical method for the quantitative determination of protein amino acids by gas-liquid chromatography (GLC) is described. All of the common protein amino acids except arginine can be readily converted into their N-isobutyloxycarbonyl (N-isoBOC) methyl ester derivatives by a simple procedure involving isobutyloxycarbonylation with isobutyl chloroformate in aqueous medium, followed by methylation with diazomethane. Arginine was converted into N-isoBOC ornithine methyl ester by treatment with arginase, followed by the above derivatization procedure. The resulting N-isoBOC methyl esters of the amino acids have good GLC properties. Complete resolution of the derivatives of 20 protein amino acids was achieved by using a dual-column system consisting of a 0.65% Poly-A-101A column and a 0.70% FFAP-Poly-A-101A (1:1, w/w) column. The reproducibility of response was found to be good for derivatives carried through the entire chemical and chromatographic procedure. The calibration graphs were linear and showed no statistical bias. The results of recovery experiments with synthetic mixtures containing known amounts of the amino acids were satisfactory, the recoveries ranging from 94.3 to 106.2%.", "contents": "Gas-liquid chromatographic analysis of protein amino acids as N-isobutyloxycarbonylamino acid methyl esters. A practical method for the quantitative determination of protein amino acids by gas-liquid chromatography (GLC) is described. All of the common protein amino acids except arginine can be readily converted into their N-isobutyloxycarbonyl (N-isoBOC) methyl ester derivatives by a simple procedure involving isobutyloxycarbonylation with isobutyl chloroformate in aqueous medium, followed by methylation with diazomethane. Arginine was converted into N-isoBOC ornithine methyl ester by treatment with arginase, followed by the above derivatization procedure. The resulting N-isoBOC methyl esters of the amino acids have good GLC properties. Complete resolution of the derivatives of 20 protein amino acids was achieved by using a dual-column system consisting of a 0.65% Poly-A-101A column and a 0.70% FFAP-Poly-A-101A (1:1, w/w) column. The reproducibility of response was found to be good for derivatives carried through the entire chemical and chromatographic procedure. The calibration graphs were linear and showed no statistical bias. The results of recovery experiments with synthetic mixtures containing known amounts of the amino acids were satisfactory, the recoveries ranging from 94.3 to 106.2%."} {"id": "PMID:1270542", "title": "Chromatography of cephalosporins on DEAE-sephadex.", "content": "A method is described for separating and quantifying new cephalosporin derivatives by means of column chromatography on DEAE-Sephadex A-25. The procedure has been used to determine some breakdown products of cefacetril.", "contents": "Chromatography of cephalosporins on DEAE-sephadex. A method is described for separating and quantifying new cephalosporin derivatives by means of column chromatography on DEAE-Sephadex A-25. The procedure has been used to determine some breakdown products of cefacetril."} {"id": "PMID:1270543", "title": "Gas chromatography of bile acids as their hexafluoroisopropyl ester-trifluoroacetyl derivatives.", "content": "Bile acids, such as cholic, chenodeoxycholic, deoxycholic, lithocholic and ursodeoxycholic acids, were allowed to react with hexafluoroisopropanol and tri-fluoracetic anhydride at 37 for 30 min. The resulting derivatives were gas chromatographed on QF-1, with flame ionization detection, and were identified by gas chromatography-mass spectrometry. Separation was good. By using this method, these acids were detected in samples of human duodenal fluid; the ratios of each were 24.4, 41.5, 24.9, 2.3 and 6.9%, respectively.", "contents": "Gas chromatography of bile acids as their hexafluoroisopropyl ester-trifluoroacetyl derivatives. Bile acids, such as cholic, chenodeoxycholic, deoxycholic, lithocholic and ursodeoxycholic acids, were allowed to react with hexafluoroisopropanol and tri-fluoracetic anhydride at 37 for 30 min. The resulting derivatives were gas chromatographed on QF-1, with flame ionization detection, and were identified by gas chromatography-mass spectrometry. Separation was good. By using this method, these acids were detected in samples of human duodenal fluid; the ratios of each were 24.4, 41.5, 24.9, 2.3 and 6.9%, respectively."} {"id": "PMID:1270553", "title": "High-performance liquid chromatographic determination of kanamycin.", "content": "A fast, selective, and precise liquid chromatographic method for simultaneous, independent determination of kanamycins A and B is described. Sample components are separated on a pellicular cation exchanger and monitored by fluorescence using post-column on-line derivatization. Less than 0.35 mug of kanamycin B can be detected in as much as 7 mug kanamycin A injected. The detection limit for kanamycin A is less than 20 ng injected. Reproducibility of the entire chromatographic system is about 1% (2 theta) based upon repeated injections of standards. Precision of repeated process sample preparation is about 6% (2 theta). Chromatographic analysis time is less than 15 min per sample.", "contents": "High-performance liquid chromatographic determination of kanamycin. A fast, selective, and precise liquid chromatographic method for simultaneous, independent determination of kanamycins A and B is described. Sample components are separated on a pellicular cation exchanger and monitored by fluorescence using post-column on-line derivatization. Less than 0.35 mug of kanamycin B can be detected in as much as 7 mug kanamycin A injected. The detection limit for kanamycin A is less than 20 ng injected. Reproducibility of the entire chromatographic system is about 1% (2 theta) based upon repeated injections of standards. Precision of repeated process sample preparation is about 6% (2 theta). Chromatographic analysis time is less than 15 min per sample."} {"id": "PMID:1270554", "title": "Chromatographic separation of cannabinoids and their monooxygenated derivatives.", "content": "delta1-Tetrahydrocannabinol, delta6-tetrahydrocannabinol, cannabinol, cannabidiol and several of their monooxygenated derivatives have been separated from each other by a combination of liquid, thin-layer and gas chromatography. Retention volumes (on Sephadex LH-20), Rf values and retention times can be recorded, and may provide guidance in the separation and identification of these known cannabinoids.", "contents": "Chromatographic separation of cannabinoids and their monooxygenated derivatives. delta1-Tetrahydrocannabinol, delta6-tetrahydrocannabinol, cannabinol, cannabidiol and several of their monooxygenated derivatives have been separated from each other by a combination of liquid, thin-layer and gas chromatography. Retention volumes (on Sephadex LH-20), Rf values and retention times can be recorded, and may provide guidance in the separation and identification of these known cannabinoids."} {"id": "PMID:1270555", "title": "Quantitative gas chromatography and gas chromatography-mass spectrometry of Cephalotaxus alkaloids.", "content": "Plants of the genus Cephalotaxus contaim many alkaloids, some of which have demonstrated antitumor activity. Analysis of crude alkaloid mixtures by gas chromatography provides quantitation of the active principles and other, non-active, alkaloids. Mass spectrometry is used to identify known alkaloids in extracts and to confirm the presence of previously unknown ones. Such data provide a means for predicting the biological activity of new plant accessions.", "contents": "Quantitative gas chromatography and gas chromatography-mass spectrometry of Cephalotaxus alkaloids. Plants of the genus Cephalotaxus contaim many alkaloids, some of which have demonstrated antitumor activity. Analysis of crude alkaloid mixtures by gas chromatography provides quantitation of the active principles and other, non-active, alkaloids. Mass spectrometry is used to identify known alkaloids in extracts and to confirm the presence of previously unknown ones. Such data provide a means for predicting the biological activity of new plant accessions."} {"id": "PMID:1270556", "title": "A quantitative gas-liquid chromatographic method for the determination of neostigmine and pyridostigmine in human plasma.", "content": "A sensitive and selective analytical method was used to measure the concentration of neostigmine and pyridostigmine in human plasma. The procedure involved preliminary ion-pair extraction of the drugs into dichloromethane, followed by concentration and anlysis of the ion-pair complex using a gas-liquid chromatographic system fitted with a nitrogen detector. Using the peak area ratio technique, pyridostigmine bromide was used as the internal standard for the quantitation of neostigmine in plasma; neostigmine bromide was the internal marker for the determination of pyridostigmine. The method depends on the thermal dequaternisation of the quaternary amines, and can be used to detect 5 ng/ml in a 3-ml plasma sample. Accurate measurement can be made at levels of 50-1000 ng/ml. This assay procedure has been applied to the separate determination of the plasma concentration of neostigmine and pyridostigmine after single administration of intravenous doses in aneasthetised patients.", "contents": "A quantitative gas-liquid chromatographic method for the determination of neostigmine and pyridostigmine in human plasma. A sensitive and selective analytical method was used to measure the concentration of neostigmine and pyridostigmine in human plasma. The procedure involved preliminary ion-pair extraction of the drugs into dichloromethane, followed by concentration and anlysis of the ion-pair complex using a gas-liquid chromatographic system fitted with a nitrogen detector. Using the peak area ratio technique, pyridostigmine bromide was used as the internal standard for the quantitation of neostigmine in plasma; neostigmine bromide was the internal marker for the determination of pyridostigmine. The method depends on the thermal dequaternisation of the quaternary amines, and can be used to detect 5 ng/ml in a 3-ml plasma sample. Accurate measurement can be made at levels of 50-1000 ng/ml. This assay procedure has been applied to the separate determination of the plasma concentration of neostigmine and pyridostigmine after single administration of intravenous doses in aneasthetised patients."} {"id": "PMID:1270557", "title": "Comparison of chromatographic methods for the analysis of glycerol esters.", "content": "Column, thin-layer and gel chromatography have been compared as methods for the analysis of glycerol esters. It was found that gel chromatography gave much easier and faster analyses of monoglyceride emulsifiers, while at the same time providing a satisfactory distribution of fractions and giving an accuracy of determination corresponding to that of the standard method for their analysis.", "contents": "Comparison of chromatographic methods for the analysis of glycerol esters. Column, thin-layer and gel chromatography have been compared as methods for the analysis of glycerol esters. It was found that gel chromatography gave much easier and faster analyses of monoglyceride emulsifiers, while at the same time providing a satisfactory distribution of fractions and giving an accuracy of determination corresponding to that of the standard method for their analysis."} {"id": "PMID:1270558", "title": "[Separation of pharmaceutical compounds using high-performance liquid chromatography. Influence of water II. (author's transl)].", "content": "The use of ternary solvent systems as mobile phases in combination with highly efficient chromatographic columns is of particular interest for the analysis of pharmaceutical and biological compounds. The solute-silanol group interactions decrease when the eluent is blended with water. Good selectivities are found with such systems.", "contents": "[Separation of pharmaceutical compounds using high-performance liquid chromatography. Influence of water II. (author's transl)]. The use of ternary solvent systems as mobile phases in combination with highly efficient chromatographic columns is of particular interest for the analysis of pharmaceutical and biological compounds. The solute-silanol group interactions decrease when the eluent is blended with water. Good selectivities are found with such systems."} {"id": "PMID:1270559", "title": "Liquid ion exchangers in reversed-phase systems for chromatography of steroidal glucosiduronic acids.", "content": "Steroidal glucosiduronic acids were chromatographed on paper by the reversed-phase technique using five different liquid ion exchangers as stationary phase and aqueous KCl as mobile phase. The relationship of mobility of the acids (Rm) to both the amount of exchanger on the paper and the concentration of KCl in the mobile phase is discussed: the relationships may be expressed as Rm=n.log [exchanger] + const. and RM=-N.LOG [KCl] + const., respectively. Migration of the acids in the presence of different exchangers is correlated by use of the equation Rm (exchanger Y)=a.Rm (exchanger X) + b. The lack of appreciable correlation between migration of the acids in a reversed-phase system and a corresponding straight-phase system is discussed and expressed by means of regression equations. The correlation coefficients and standard errors of estimate from these equations provide useful indices for selecting two solvent systems that are to be used sequentially to obtain maximal resolution of a group of compounds. deltaRm values obtained for various functional groups with reversed-phase and straight-phase techniques are compared.", "contents": "Liquid ion exchangers in reversed-phase systems for chromatography of steroidal glucosiduronic acids. Steroidal glucosiduronic acids were chromatographed on paper by the reversed-phase technique using five different liquid ion exchangers as stationary phase and aqueous KCl as mobile phase. The relationship of mobility of the acids (Rm) to both the amount of exchanger on the paper and the concentration of KCl in the mobile phase is discussed: the relationships may be expressed as Rm=n.log [exchanger] + const. and RM=-N.LOG [KCl] + const., respectively. Migration of the acids in the presence of different exchangers is correlated by use of the equation Rm (exchanger Y)=a.Rm (exchanger X) + b. The lack of appreciable correlation between migration of the acids in a reversed-phase system and a corresponding straight-phase system is discussed and expressed by means of regression equations. The correlation coefficients and standard errors of estimate from these equations provide useful indices for selecting two solvent systems that are to be used sequentially to obtain maximal resolution of a group of compounds. deltaRm values obtained for various functional groups with reversed-phase and straight-phase techniques are compared."} {"id": "PMID:1270560", "title": "Determination of benomyl and 2-(4-thiazolyl) benzimidazole in plant tissues by high-performance liquid chromatography using fluorimetric detection.", "content": "Methods for determining benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate] residues in plant tissues involve isolation of the residue by extraction with ethyl acetate, hydrolysis of the extracted residue to 2-aminobenzimidazole and final determination by high-performance liquid chromatography using a fluorimeter. 2-(4-Thiazolyl) benzimidazole is also determined by a similar procedure without hydrolysis. The sensitivities of these methods are 0.02 ppm for benomyl and 0.001 ppm for 2-(4-thiazolyl) benzimidazole. Recoveries of these compounds from various plant tissues were 90.5-102.9%. No interference with these methods from the plant tissues tested was found.", "contents": "Determination of benomyl and 2-(4-thiazolyl) benzimidazole in plant tissues by high-performance liquid chromatography using fluorimetric detection. Methods for determining benomyl [methyl 1-(butylcarbamoyl)-2-benzimidazole carbamate] residues in plant tissues involve isolation of the residue by extraction with ethyl acetate, hydrolysis of the extracted residue to 2-aminobenzimidazole and final determination by high-performance liquid chromatography using a fluorimeter. 2-(4-Thiazolyl) benzimidazole is also determined by a similar procedure without hydrolysis. The sensitivities of these methods are 0.02 ppm for benomyl and 0.001 ppm for 2-(4-thiazolyl) benzimidazole. Recoveries of these compounds from various plant tissues were 90.5-102.9%. No interference with these methods from the plant tissues tested was found."} {"id": "PMID:1270561", "title": "Determination of the carotenoid phytoene in blood by high-pressure liquid chromatography.", "content": "A sensitive and specific high-pressure liquid chromatographic assay was developed for the determination of phytoene in blood with an overall recovery of 86 +/- 6.0% and a limit of detection of 50-100 ng per ml of blood. This method provides for rapid and simple quantitation of phytoene using 1 ml or less of blood. The assay was used in the determination of phytoene blood levels in the dog following intravenous and oral administration of 10-mg/kg doses.", "contents": "Determination of the carotenoid phytoene in blood by high-pressure liquid chromatography. A sensitive and specific high-pressure liquid chromatographic assay was developed for the determination of phytoene in blood with an overall recovery of 86 +/- 6.0% and a limit of detection of 50-100 ng per ml of blood. This method provides for rapid and simple quantitation of phytoene using 1 ml or less of blood. The assay was used in the determination of phytoene blood levels in the dog following intravenous and oral administration of 10-mg/kg doses."} {"id": "PMID:1270567", "title": "Rapid screening and confirmation of amphetamine, methamphetamine, methadone, and methadone metabolite in urine by gas/thin layer chromatography.", "content": "A method suitable for large scale screening and confirmation of urine speciments for amphetamine, methamphetamine, methadone, and its primary metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenlypyrrolidine) is described. The drugs are extracted from alkaline urine into an organic solvent. The amphetamine drugs are then back-extracted into a small volume of acid and identified by gas chromatography both as free bases on a 10% Apiezon L-10% KOH column and as their trifluoracetamide derivatives on a 3% OV-17 column. The organic layer, which still contains methadone and its primary metabolite, is analyzed by split-sample thin-layer chromatography using two solvent systems: ethyl acetate: methylene cloride: concentrated ammonium hydroxide (90:10:0.7) and methanol: chloroform: concentrated ammonium hydroxide (74:25:0.8). These solvent systems separate methadone from its primary metabolite without interference from other drugs or urinary substances.", "contents": "Rapid screening and confirmation of amphetamine, methamphetamine, methadone, and methadone metabolite in urine by gas/thin layer chromatography. A method suitable for large scale screening and confirmation of urine speciments for amphetamine, methamphetamine, methadone, and its primary metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenlypyrrolidine) is described. The drugs are extracted from alkaline urine into an organic solvent. The amphetamine drugs are then back-extracted into a small volume of acid and identified by gas chromatography both as free bases on a 10% Apiezon L-10% KOH column and as their trifluoracetamide derivatives on a 3% OV-17 column. The organic layer, which still contains methadone and its primary metabolite, is analyzed by split-sample thin-layer chromatography using two solvent systems: ethyl acetate: methylene cloride: concentrated ammonium hydroxide (90:10:0.7) and methanol: chloroform: concentrated ammonium hydroxide (74:25:0.8). These solvent systems separate methadone from its primary metabolite without interference from other drugs or urinary substances."} {"id": "PMID:1270568", "title": "Constituents of peppers: IV. The hydrocarbons of pepper essential oil.", "content": "Twenty-six hydrocarbons were identified in the essential oil of black pepper. Three of these are sesquiterpenes which have not been reported previously as occurring in this oil (beta-cubebene, alpha-guaiene and gamma-cadinene). Some other hydrocarbon constituents mentioned in the literature were absent in our pepper oil.", "contents": "Constituents of peppers: IV. The hydrocarbons of pepper essential oil. Twenty-six hydrocarbons were identified in the essential oil of black pepper. Three of these are sesquiterpenes which have not been reported previously as occurring in this oil (beta-cubebene, alpha-guaiene and gamma-cadinene). Some other hydrocarbon constituents mentioned in the literature were absent in our pepper oil."} {"id": "PMID:1270569", "title": "Quantitative gas-liquid chromatography of iproniazid and iproclozide.", "content": "Analytically packed columns prepared with Versamid-930, Versamid-900, XE-60, and OV-225 as stationary phases were examined for quantitative gas-liquid chromatography of the potent monamine oxydase inhibitor (MAOI) drugs iproniazid and iproclozide. With the aid of chemically related substances as internal standards, response ratios were determined and linearities calculated by regression analysis. Using the 2-butyl analogs of compounds all four column systems permit quantitation of iproniazid and iproclozide with a percent standard deviation sigmaK of about 1% or less.", "contents": "Quantitative gas-liquid chromatography of iproniazid and iproclozide. Analytically packed columns prepared with Versamid-930, Versamid-900, XE-60, and OV-225 as stationary phases were examined for quantitative gas-liquid chromatography of the potent monamine oxydase inhibitor (MAOI) drugs iproniazid and iproclozide. With the aid of chemically related substances as internal standards, response ratios were determined and linearities calculated by regression analysis. Using the 2-butyl analogs of compounds all four column systems permit quantitation of iproniazid and iproclozide with a percent standard deviation sigmaK of about 1% or less."} {"id": "PMID:1270574", "title": "Gastric inhibitory polypeptide (GIP) in chronic pancreatitis.", "content": "The plasma gastric inhibitory polypeptide (GIP), pancreatic glucagon-like immunoreactivity (PGLI), and gut glucagon-like immunoreactivity (GGLI) responses to oral glucose have been measured in five patients with chronic pancreatitis (with diabetic glucose tolerance tests) and in matched nondiabetic controls. Plasma GIP levels rise rapidly after glucose ingestion before changes in circulating glucose and insulin concentration. Patients with pancreatitis have a greater than normal GIP response to oral glucose, which may account for the relatively unimparied insulin response to oral glucose in these patients compared with that to iv glucose, as has been previously found. Patients with pancreatitis also have a paradoxical rise in PGLI and an exaggerated rise in GGLI concentration following oral glucose.", "contents": "Gastric inhibitory polypeptide (GIP) in chronic pancreatitis. The plasma gastric inhibitory polypeptide (GIP), pancreatic glucagon-like immunoreactivity (PGLI), and gut glucagon-like immunoreactivity (GGLI) responses to oral glucose have been measured in five patients with chronic pancreatitis (with diabetic glucose tolerance tests) and in matched nondiabetic controls. Plasma GIP levels rise rapidly after glucose ingestion before changes in circulating glucose and insulin concentration. Patients with pancreatitis have a greater than normal GIP response to oral glucose, which may account for the relatively unimparied insulin response to oral glucose in these patients compared with that to iv glucose, as has been previously found. Patients with pancreatitis also have a paradoxical rise in PGLI and an exaggerated rise in GGLI concentration following oral glucose."} {"id": "PMID:1270575", "title": "Volume of sella turcica in normal subjects and in patients with primary hypothyroidism and hyperthyroidism.", "content": "In an attempt to assess a possible relationship between pituitary size and TSH secretion, the volume of sella turcica was measured in 570 subjects, 26 primary hypothyroid patients, and 34 thyrotoxic patients. The volume of sella turcica, measured by a 3-dimensional approach, increased progressively with age until 20 years of age and was rather constant thereafter in normal subjects. In thyrotoxic patients, the volume of sella turcica was normal in spite of decreased plasma TSH concentration. In contrast, 81% of primary hypothyroid patients had an abnormal enlargement of the sella turcica. The magnitude of an increase of sella turcica inversely related with a decrease in serum T4 and T3 concentrations. On the other hand, the magnitude of an increase of sella turcica correlated well with an increase of circulating TSH. We suggest that an increase of sella turcica indirectly reflects an increase in pituitary size and TSH-secreting capacity, possibly due to hypertrophy and hyperplasia of TSH cells in primary hypothyroid patients.", "contents": "Volume of sella turcica in normal subjects and in patients with primary hypothyroidism and hyperthyroidism. In an attempt to assess a possible relationship between pituitary size and TSH secretion, the volume of sella turcica was measured in 570 subjects, 26 primary hypothyroid patients, and 34 thyrotoxic patients. The volume of sella turcica, measured by a 3-dimensional approach, increased progressively with age until 20 years of age and was rather constant thereafter in normal subjects. In thyrotoxic patients, the volume of sella turcica was normal in spite of decreased plasma TSH concentration. In contrast, 81% of primary hypothyroid patients had an abnormal enlargement of the sella turcica. The magnitude of an increase of sella turcica inversely related with a decrease in serum T4 and T3 concentrations. On the other hand, the magnitude of an increase of sella turcica correlated well with an increase of circulating TSH. We suggest that an increase of sella turcica indirectly reflects an increase in pituitary size and TSH-secreting capacity, possibly due to hypertrophy and hyperplasia of TSH cells in primary hypothyroid patients."} {"id": "PMID:1270576", "title": "Radioimmunoassay for 3,3',5'-triiodo-L-thyronine in unextracted serum: method and clinical results.", "content": "Serum 3,3',5'-triiodothyronine (rT3) was measured with a radioimmunoassay in unextracted serum. The assay was specific and reproducible. The coefficients of variation for 3 different sera known for high, normal, and low rT3 concentrations between assays were 4, 6, and 9% within assays 4, 9, and 7%, respectively. In euthyroid subjects 20 to 60 years old, rT3 was 450 +/- 200 pg/ml (mean +/- 2 SD.n = 83). Serum rT3 was found to be increased in hyperthyroidism (range: 762-2581 pg-ml; n = 11) but also in acute and chronic illness (up to 2400 pg/ml; n = 24) and in anorexia nervosa (536-1058 pg/ml; n = 7). In the latter two situations there was mostly an inverse change in serum 3,5,3'-triiodothyronine (T3) which was in the low normal range or decreased. These findings suggest a metabolic control of thyroxine deiodination. A low serum rT3 was found in 9 of 12 hypothyroid patients and in the serum of 1 chronically ill patient. Long-term treatment (1-7 years) with lithium carbonate slightly reduced serum rT3, although the changes were inside the normal range. Kidney function was not found to be necessary for its production as anephric patients had normal rT3 values. In addition, hemodialysis increased serum rT3, which is probably due to the heparin therapy.", "contents": "Radioimmunoassay for 3,3',5'-triiodo-L-thyronine in unextracted serum: method and clinical results. Serum 3,3',5'-triiodothyronine (rT3) was measured with a radioimmunoassay in unextracted serum. The assay was specific and reproducible. The coefficients of variation for 3 different sera known for high, normal, and low rT3 concentrations between assays were 4, 6, and 9% within assays 4, 9, and 7%, respectively. In euthyroid subjects 20 to 60 years old, rT3 was 450 +/- 200 pg/ml (mean +/- 2 SD.n = 83). Serum rT3 was found to be increased in hyperthyroidism (range: 762-2581 pg-ml; n = 11) but also in acute and chronic illness (up to 2400 pg/ml; n = 24) and in anorexia nervosa (536-1058 pg/ml; n = 7). In the latter two situations there was mostly an inverse change in serum 3,5,3'-triiodothyronine (T3) which was in the low normal range or decreased. These findings suggest a metabolic control of thyroxine deiodination. A low serum rT3 was found in 9 of 12 hypothyroid patients and in the serum of 1 chronically ill patient. Long-term treatment (1-7 years) with lithium carbonate slightly reduced serum rT3, although the changes were inside the normal range. Kidney function was not found to be necessary for its production as anephric patients had normal rT3 values. In addition, hemodialysis increased serum rT3, which is probably due to the heparin therapy."} {"id": "PMID:1270577", "title": "Body composition in Cushing's disease.", "content": "Lean body mass and body fat mass were estimated in 12 patients with Cushing's disease before treatment, in 5 of these after correction of the adrenal hyperfunction, and in 23 patients with simple obesity. The methods used, whole-body counting of 40K and tritiated water dilution, may in Cushing's disease over- and underestimate, respectively, the body fat mass and may therefore be considered to give upper and lower limits of that entity. By a comparison with the results in simple obesity, we conclude that the total body fat mass generally is increased in patients with Cushing's disease.", "contents": "Body composition in Cushing's disease. Lean body mass and body fat mass were estimated in 12 patients with Cushing's disease before treatment, in 5 of these after correction of the adrenal hyperfunction, and in 23 patients with simple obesity. The methods used, whole-body counting of 40K and tritiated water dilution, may in Cushing's disease over- and underestimate, respectively, the body fat mass and may therefore be considered to give upper and lower limits of that entity. By a comparison with the results in simple obesity, we conclude that the total body fat mass generally is increased in patients with Cushing's disease."} {"id": "PMID:1270578", "title": "Comparison of the effectiveness of various routes of insulin injection: insulin levels and glucose response in normal subjects.", "content": "The difference in absorption of insulin and its glucose lowering-effect after the administration of crystalline insulin by the intravenous, intramuscular, and subcutaneous routes was compared in 14 lean normal subjects. Insulin in a dose of 0.1 U/kg body weight was given by the three different routes. Blood was drawn from the opposite arm at regular intervals for the determination of insulin, glucose, glucagon, cortisol, and potassium. Intravenous insulin produced the highest pharmacological level of insulin in 2 minutes (2099 +/- 414 muU/ml) with marked hypoglycemia at 30 minutes (a 68% drop). Intravenous insulin injection produced an increase in plasma glucagon and cortisol reaching a 2-fold increase above the fasting level 30 minutes after the glucose nadir. An equivalent amount of intramuscular insulin produced a maximal increase in plasma insulin at 50 minutes (45 +/- 4 muU/ml) and caused a 35% drop in plasma glucose at 60 minutes, which effects were greater than those caused by subcutaneous injection (highest IRI = 36 +/- 3.5 muU/ml and 23% glucose drop at 180 minutes). No significant increase in glucagon or cortisol was noted with equivalent amounts of subcutaneous or intramuscular insulin injection. Our studies suggest that, in normal lean subjects, insulin injection by the intramuscular route provides a faster absorption of insulin with a concomitant greater drop in plasma glucose than does injection by the subcutaneous route.", "contents": "Comparison of the effectiveness of various routes of insulin injection: insulin levels and glucose response in normal subjects. The difference in absorption of insulin and its glucose lowering-effect after the administration of crystalline insulin by the intravenous, intramuscular, and subcutaneous routes was compared in 14 lean normal subjects. Insulin in a dose of 0.1 U/kg body weight was given by the three different routes. Blood was drawn from the opposite arm at regular intervals for the determination of insulin, glucose, glucagon, cortisol, and potassium. Intravenous insulin produced the highest pharmacological level of insulin in 2 minutes (2099 +/- 414 muU/ml) with marked hypoglycemia at 30 minutes (a 68% drop). Intravenous insulin injection produced an increase in plasma glucagon and cortisol reaching a 2-fold increase above the fasting level 30 minutes after the glucose nadir. An equivalent amount of intramuscular insulin produced a maximal increase in plasma insulin at 50 minutes (45 +/- 4 muU/ml) and caused a 35% drop in plasma glucose at 60 minutes, which effects were greater than those caused by subcutaneous injection (highest IRI = 36 +/- 3.5 muU/ml and 23% glucose drop at 180 minutes). No significant increase in glucagon or cortisol was noted with equivalent amounts of subcutaneous or intramuscular insulin injection. Our studies suggest that, in normal lean subjects, insulin injection by the intramuscular route provides a faster absorption of insulin with a concomitant greater drop in plasma glucose than does injection by the subcutaneous route."} {"id": "PMID:1270579", "title": "Early skeletal effect of alkali therapy upon the osteomalacia of renal tubular acidosis.", "content": "The administration of alkaline agents to a 16-year-old girl with severe renal tubular acidosis and osteomalacia caused an almost immediate rise of the urinary excretion of total hydroxyproline. The increment of the dyalizable fraction predominated over the nondyalizable component. Gradually serum phosphate and serum alkaline phosphatase increased whereas urinary calcium and magnesium and phosphate clearance declined. Serum PTH remained elevated throughout. We suggest that the correction of the metabolic acidosis might increase the transport of phosphate and calcium across the functional bone membrane leading to a rapid deposition of lime salts in the uncalcified matrix with a concomitant increase in bone collagen turnover.", "contents": "Early skeletal effect of alkali therapy upon the osteomalacia of renal tubular acidosis. The administration of alkaline agents to a 16-year-old girl with severe renal tubular acidosis and osteomalacia caused an almost immediate rise of the urinary excretion of total hydroxyproline. The increment of the dyalizable fraction predominated over the nondyalizable component. Gradually serum phosphate and serum alkaline phosphatase increased whereas urinary calcium and magnesium and phosphate clearance declined. Serum PTH remained elevated throughout. We suggest that the correction of the metabolic acidosis might increase the transport of phosphate and calcium across the functional bone membrane leading to a rapid deposition of lime salts in the uncalcified matrix with a concomitant increase in bone collagen turnover."} {"id": "PMID:1270580", "title": "A testosterone-producing adrenal cortical adenoma in an elderly woman.", "content": "A 76-year-old woman with virilization had menopausal levels of circulating LH and FSH, and a markedly elevated concentration of plasma testosterone (9130 pg/ml) into the range for adult men. Plasma cortisol and androstenedione levels andurinary 17-ketosteroid secretion were normal. Ethinyl estradiol suppressed plasma testosterone, LH, and FSH levels into the normal range for premenopausal women, but the testosterone concentration was unaffected by the administration of dexamethasone or ACTH. Retrograde venous sampling and angiography localized a right adrenal adenoma preoperatively. Following adrenalectomy, there was a prompt fall in testosterone, but there was no change in the LH concentration. Thus, this patient had an adrenal adenoma which secreted only testosterone and appeared to be gonadotropin-responsive. Testosterone levels in the adult male range failed to suppress gonadotropins. The significance of these findings is discussed.", "contents": "A testosterone-producing adrenal cortical adenoma in an elderly woman. A 76-year-old woman with virilization had menopausal levels of circulating LH and FSH, and a markedly elevated concentration of plasma testosterone (9130 pg/ml) into the range for adult men. Plasma cortisol and androstenedione levels andurinary 17-ketosteroid secretion were normal. Ethinyl estradiol suppressed plasma testosterone, LH, and FSH levels into the normal range for premenopausal women, but the testosterone concentration was unaffected by the administration of dexamethasone or ACTH. Retrograde venous sampling and angiography localized a right adrenal adenoma preoperatively. Following adrenalectomy, there was a prompt fall in testosterone, but there was no change in the LH concentration. Thus, this patient had an adrenal adenoma which secreted only testosterone and appeared to be gonadotropin-responsive. Testosterone levels in the adult male range failed to suppress gonadotropins. The significance of these findings is discussed."} {"id": "PMID:1270581", "title": "Testicular chromosomal mosaicism and infertility.", "content": "A healthy young man with azoospermia and no other endocrinological abnormalties was shown to have chromosomal mosaicism with the cytogenetic errors found only in testicular tissue. Three clones of cells were identified in both meiosis I and meiosis II by cytogenetic analysis of direct testicular smears. Peripheral blood karyotypes and buccal smear preparations revealed no abnormalities. It is postulated that the gonadal cytogenetic defects account for this patient's azoospermia. In addition, it is hypothesized that this type of incomplete spermatogenesis nonetheless produces sufficiet feedback material (\"inhibin\") so that FSH levels are not affected.", "contents": "Testicular chromosomal mosaicism and infertility. A healthy young man with azoospermia and no other endocrinological abnormalties was shown to have chromosomal mosaicism with the cytogenetic errors found only in testicular tissue. Three clones of cells were identified in both meiosis I and meiosis II by cytogenetic analysis of direct testicular smears. Peripheral blood karyotypes and buccal smear preparations revealed no abnormalities. It is postulated that the gonadal cytogenetic defects account for this patient's azoospermia. In addition, it is hypothesized that this type of incomplete spermatogenesis nonetheless produces sufficiet feedback material (\"inhibin\") so that FSH levels are not affected."} {"id": "PMID:1270582", "title": "Urine aldosterone radioimmunoassay: validation of a method without chromatography.", "content": "A simplified radioimmunoassay of urinary aldosterone is reported. Acid-hydrolyzed urine was extracted with dichloromethane and the extract assayed without further purification, Urinary aldosterone values in patients with Cushing's syndrome, low and normal-renin essential hypertension, congenital adrenal hyperplasia, and primary aldosteronism determined by this method agreed closely (r = 0.95, P less than 0.01) with values obtained using a standardized chromatographic method. This simplified assay represents a significant advance in out capabilitites for evaluating patients for abnormalities in aldosterone physiology.", "contents": "Urine aldosterone radioimmunoassay: validation of a method without chromatography. A simplified radioimmunoassay of urinary aldosterone is reported. Acid-hydrolyzed urine was extracted with dichloromethane and the extract assayed without further purification, Urinary aldosterone values in patients with Cushing's syndrome, low and normal-renin essential hypertension, congenital adrenal hyperplasia, and primary aldosteronism determined by this method agreed closely (r = 0.95, P less than 0.01) with values obtained using a standardized chromatographic method. This simplified assay represents a significant advance in out capabilitites for evaluating patients for abnormalities in aldosterone physiology."} {"id": "PMID:1270583", "title": "Depression of growth hormone and cortisol response to insulin-induced hypoglycemia after prolonged oral delta-9-tetrahydrocannabinol administration in man.", "content": "Six hospitalized volunteer male subjects were given insulin, 0.15 U/kg, before and after 14 days of administration of delta-9-tetrahydrocannabinol (THC) at a dose of 210 mg/day. A diminished maximal serum human growth hormone (GH) increase followed the prolonged THC ingestion. The mean maximal GH response was: 52.6 ng/ml +/- 8.7 (+/-SE) before THC and 18.8 ng/ml +/- 6.7 (+/-SE) during THC, P less than 0.01; corresponding cortisol responses were 20.1 mug/dl +/- 3.0 before THC and 10.0 mug/dl +/- 1.1 during THC, P less than 0.05. The data suggest suppression of the hypothalamic-pituitary axis after prolonged high dose THC use. This is consistent with other reported endocrine effects of marijuana in man.", "contents": "Depression of growth hormone and cortisol response to insulin-induced hypoglycemia after prolonged oral delta-9-tetrahydrocannabinol administration in man. Six hospitalized volunteer male subjects were given insulin, 0.15 U/kg, before and after 14 days of administration of delta-9-tetrahydrocannabinol (THC) at a dose of 210 mg/day. A diminished maximal serum human growth hormone (GH) increase followed the prolonged THC ingestion. The mean maximal GH response was: 52.6 ng/ml +/- 8.7 (+/-SE) before THC and 18.8 ng/ml +/- 6.7 (+/-SE) during THC, P less than 0.01; corresponding cortisol responses were 20.1 mug/dl +/- 3.0 before THC and 10.0 mug/dl +/- 1.1 during THC, P less than 0.05. The data suggest suppression of the hypothalamic-pituitary axis after prolonged high dose THC use. This is consistent with other reported endocrine effects of marijuana in man."} {"id": "PMID:1270584", "title": "Cortisol-dihydrotachysterol antagonism in a patient with hypoparathyroidism and adrenal insufficiency: apparent inhibition of bone resorption.", "content": "This report describes a case of chronic mucocutaneous candidiasis with associated hypoparathyroidism and acutely developed adrenocortical insufficiency. The latter was heralded by hypercalcemia. Upon the institution of cortisol therapy, while still under the effects of a vitamin D analog dihydrotachysterol (DHT), the patient exhibited severe hypocalcemia and tetany. Since calcium intake was minimal during this period of presumed corticosteroid-DHT antagonism, it is suggested that the cortisol disturbed calcium homeostasis by in inhibiting bone calcium resorption.", "contents": "Cortisol-dihydrotachysterol antagonism in a patient with hypoparathyroidism and adrenal insufficiency: apparent inhibition of bone resorption. This report describes a case of chronic mucocutaneous candidiasis with associated hypoparathyroidism and acutely developed adrenocortical insufficiency. The latter was heralded by hypercalcemia. Upon the institution of cortisol therapy, while still under the effects of a vitamin D analog dihydrotachysterol (DHT), the patient exhibited severe hypocalcemia and tetany. Since calcium intake was minimal during this period of presumed corticosteroid-DHT antagonism, it is suggested that the cortisol disturbed calcium homeostasis by in inhibiting bone calcium resorption."} {"id": "PMID:1270585", "title": "In vitro bioassay of LH in human serum: the rat interstitial cell testosterone (RICT) assay.", "content": "A sensitive bioassay for serum LH and hCG has been developed by utilization of the testosterone response of collagenase-dispersed rat Leydig cells to gonadotropic stimulation in vitro. Testosterone production by dispersed interstitial cells is stimulated by human, ovine, bovine, porcine, rat and rabbit LH, and by hCG and pregnant mare serum gonadotropin. The rat testis interstitial cell assay gives parallel dose-response curves for all steroidogenic gonadotropins tested, and thus permits cross-species comparison of the intrinsic biological activities of native and modified gonadotropins. The sensitivity of the rat interstitial cell bioassay is equal to or higher than that of radioimmunoassay, with detection limits of 50 muU for hMG and 20 muU for hCG. The optimum conditions for bioassay of serum gonadotropins were provided by incubation of dispersed interstitial cells in the presence of 1-methyl 3-isobutyl xanthine with the addition of gonadotropin-free serum or 5% BSA to ensure a constant proportion of serum protein in all assay samples and standards. Assays performed under these conditions gave parallel dose-response curves and identical maximum responses to both standards and serum samples containing endogenous LH or hCG. All responses to human gonadotropin standards and serum samples in the bioassay were abolished by incubation in the presence of antisera to LH or hCG. This sensitive and specific method permits bioassay of basal levels of LH in male and female serum, and of the higher gonadotropin levels in postmenopausal and pregnant subjects after appropriate dilution of the serum samples. For normal men and women, serum samples of 25-100 mul are employed, while volumes of 1-20 mul are adequate for assay of LH in postmenopausal or hypogonadal subjects. Serum LH values in hypopituitary and oral contraceptive-treated subjects were usually undetectable, while LH levels in normal subjects were always measurable with good precision. The within-assay coefficient of variation for measurement of a normal male plasma pool (30 mU/ml) was +/- 10%, and the between-assay variation was +/- 15%. The precision of the assay (lambda) was 0.035 +/- 0.015 (n = 72). In 42 normal females, the bio: immuno (B:I) ratio for serum LH was 1.20 +/- 0.40 (SD), and no consistent change in ratio was observed throughout the menstrual cycle. By contrast, significantly higher B:I ratios were observed in normal males (2.5 +/- 0.4), postmenopausal females (2.6 +/- 0.6) and patients with Turner's syndrome (2.6 +/- 0.6). These findings suggest that the LH circulating in normal female plasma is similar in biological and immunological activity to hMG, whereas the LH present in normal male plasma and in states of increased gonadotropin secretion has a relatively higher biological activity. The rat interstitial cell bioassay provides for the first time a practical and precise assay for measurement of the biologically active LH levels in serum of normal biologically active LH levels in serum of normal human subjects.", "contents": "In vitro bioassay of LH in human serum: the rat interstitial cell testosterone (RICT) assay. A sensitive bioassay for serum LH and hCG has been developed by utilization of the testosterone response of collagenase-dispersed rat Leydig cells to gonadotropic stimulation in vitro. Testosterone production by dispersed interstitial cells is stimulated by human, ovine, bovine, porcine, rat and rabbit LH, and by hCG and pregnant mare serum gonadotropin. The rat testis interstitial cell assay gives parallel dose-response curves for all steroidogenic gonadotropins tested, and thus permits cross-species comparison of the intrinsic biological activities of native and modified gonadotropins. The sensitivity of the rat interstitial cell bioassay is equal to or higher than that of radioimmunoassay, with detection limits of 50 muU for hMG and 20 muU for hCG. The optimum conditions for bioassay of serum gonadotropins were provided by incubation of dispersed interstitial cells in the presence of 1-methyl 3-isobutyl xanthine with the addition of gonadotropin-free serum or 5% BSA to ensure a constant proportion of serum protein in all assay samples and standards. Assays performed under these conditions gave parallel dose-response curves and identical maximum responses to both standards and serum samples containing endogenous LH or hCG. All responses to human gonadotropin standards and serum samples in the bioassay were abolished by incubation in the presence of antisera to LH or hCG. This sensitive and specific method permits bioassay of basal levels of LH in male and female serum, and of the higher gonadotropin levels in postmenopausal and pregnant subjects after appropriate dilution of the serum samples. For normal men and women, serum samples of 25-100 mul are employed, while volumes of 1-20 mul are adequate for assay of LH in postmenopausal or hypogonadal subjects. Serum LH values in hypopituitary and oral contraceptive-treated subjects were usually undetectable, while LH levels in normal subjects were always measurable with good precision. The within-assay coefficient of variation for measurement of a normal male plasma pool (30 mU/ml) was +/- 10%, and the between-assay variation was +/- 15%. The precision of the assay (lambda) was 0.035 +/- 0.015 (n = 72). In 42 normal females, the bio: immuno (B:I) ratio for serum LH was 1.20 +/- 0.40 (SD), and no consistent change in ratio was observed throughout the menstrual cycle. By contrast, significantly higher B:I ratios were observed in normal males (2.5 +/- 0.4), postmenopausal females (2.6 +/- 0.6) and patients with Turner's syndrome (2.6 +/- 0.6). These findings suggest that the LH circulating in normal female plasma is similar in biological and immunological activity to hMG, whereas the LH present in normal male plasma and in states of increased gonadotropin secretion has a relatively higher biological activity. The rat interstitial cell bioassay provides for the first time a practical and precise assay for measurement of the biologically active LH levels in serum of normal biologically active LH levels in serum of normal human subjects."} {"id": "PMID:1270586", "title": "A comparison of plasma TSH levels in patients with diffuse and nodular non-toxic goiter.", "content": "Plasma TSH levels were measured in 115 euthyroid patients with simple goiter, of whom 52 had diffuse and 63 nodular enlargement of the thyroid gland, and in 191 euthyroid patients without goiter. There was no significant difference between the plasma TSH levels in the patients with diffuse goiter and the non-goitrous controls, implying that the maintenance of diffuse hyperplasia is not dependent upon a raised level of plasma TSH. On the other hand, plasma TSH levels in the patients with nodular goiter were significantly lower than those recorded in either the patients with diffuse goiter (P less than 0.01) or in the patients without goiter (P less than 0.0001), supporting the view that thyroid function may be autonomous in nodular goiters.", "contents": "A comparison of plasma TSH levels in patients with diffuse and nodular non-toxic goiter. Plasma TSH levels were measured in 115 euthyroid patients with simple goiter, of whom 52 had diffuse and 63 nodular enlargement of the thyroid gland, and in 191 euthyroid patients without goiter. There was no significant difference between the plasma TSH levels in the patients with diffuse goiter and the non-goitrous controls, implying that the maintenance of diffuse hyperplasia is not dependent upon a raised level of plasma TSH. On the other hand, plasma TSH levels in the patients with nodular goiter were significantly lower than those recorded in either the patients with diffuse goiter (P less than 0.01) or in the patients without goiter (P less than 0.0001), supporting the view that thyroid function may be autonomous in nodular goiters."} {"id": "PMID:1270587", "title": "Circannual cycle in plasma testosterone levels in man.", "content": "In a groups of 15 healthy male subjects a statistically significant circannual cycle in plasma testosterone levels was assessed by sampling blood at 3-monthly intervals. Peak levels were found in summer and early autumn and a nadir in the winter and early spring.", "contents": "Circannual cycle in plasma testosterone levels in man. In a groups of 15 healthy male subjects a statistically significant circannual cycle in plasma testosterone levels was assessed by sampling blood at 3-monthly intervals. Peak levels were found in summer and early autumn and a nadir in the winter and early spring."} {"id": "PMID:1270588", "title": "Amniotic fluid reactivity detected by somatomedin C radioreceptor assay: correlation with growth hormone, prolactin and fetal renal maturation.", "content": "Amniotic fluid was assayed by a radioreceptor assay utilizing 125I-somatomedin C and placental membranes. Growth hormone and prolactin levels were measured by radioimmunoassay at different gestational ages (8-41 weeks). Somatomedin receptor activity, growth hormone, and prolactin reached high levels during early gestation (8-26 weeks) displaying different patterns of appearance which reflect fetal serum levels of these hormones. After 26 weeks gestation all these hormones decreased in concentration. This decrease showed a strong correlation with fetal renal maturation as measured by amniotic fluid creatinine levels.", "contents": "Amniotic fluid reactivity detected by somatomedin C radioreceptor assay: correlation with growth hormone, prolactin and fetal renal maturation. Amniotic fluid was assayed by a radioreceptor assay utilizing 125I-somatomedin C and placental membranes. Growth hormone and prolactin levels were measured by radioimmunoassay at different gestational ages (8-41 weeks). Somatomedin receptor activity, growth hormone, and prolactin reached high levels during early gestation (8-26 weeks) displaying different patterns of appearance which reflect fetal serum levels of these hormones. After 26 weeks gestation all these hormones decreased in concentration. This decrease showed a strong correlation with fetal renal maturation as measured by amniotic fluid creatinine levels."} {"id": "PMID:1270589", "title": "alpha and beta glycoprotein hormone subunits (hLH, hFSH, hCG) in the serum and pituitary of the human fetus.", "content": "Utilizing specific radioimmunoassay and gel chromatographic separation methods, the concentration of a glycoprotein hormone subunit and the beta subunit of hCG, hLH, and hFSH was determined. The alpha glycoprotein hormone subunit is present throughout gestation in the serum and pituitary of the human fetus; little or no subunit is apparent in contrast to that of intact LH and FSH.", "contents": "alpha and beta glycoprotein hormone subunits (hLH, hFSH, hCG) in the serum and pituitary of the human fetus. Utilizing specific radioimmunoassay and gel chromatographic separation methods, the concentration of a glycoprotein hormone subunit and the beta subunit of hCG, hLH, and hFSH was determined. The alpha glycoprotein hormone subunit is present throughout gestation in the serum and pituitary of the human fetus; little or no subunit is apparent in contrast to that of intact LH and FSH."} {"id": "PMID:1270590", "title": "Three strains of influenza A virus (H3N2): interferon sensitivity in vitro and interferon production in volunteers.", "content": "Three antigenic variants of the H3N2 subtype of wild-type influenza A virus (representing the years 1968, 1972, and 1974) were examined for their sensitivity to interferon and for their ability to induce local respiratory tract interferon in volunteers. In addition, the time of appearance of symptoms in infected volunteers was correlated with the patterns of virus shedding and interferon production. The sensitivity to interferon and the ability to stimulate nasopharyngeal interferon were similarly high for all three strains. Symptomatic illness, peak virus shedding, and peak interferon response all occurred within a 26-h period. These findings imply that interferon or its inducers theoretically could be protective if applied prophylactically, but would be less efficacious when used therapeutically.", "contents": "Three strains of influenza A virus (H3N2): interferon sensitivity in vitro and interferon production in volunteers. Three antigenic variants of the H3N2 subtype of wild-type influenza A virus (representing the years 1968, 1972, and 1974) were examined for their sensitivity to interferon and for their ability to induce local respiratory tract interferon in volunteers. In addition, the time of appearance of symptoms in infected volunteers was correlated with the patterns of virus shedding and interferon production. The sensitivity to interferon and the ability to stimulate nasopharyngeal interferon were similarly high for all three strains. Symptomatic illness, peak virus shedding, and peak interferon response all occurred within a 26-h period. These findings imply that interferon or its inducers theoretically could be protective if applied prophylactically, but would be less efficacious when used therapeutically."} {"id": "PMID:1270591", "title": "Blood culture technique based on centrifugation: clinical evaluation.", "content": "A total of 1,000 blood samples from patients suspected of having a bacteremia were analyzed concurrently, where possible, by three methods: (i) Trypticase soy broth with sodium polyanethol sulfonate and a CO2 atmosphere: (ii) pour plates with either brain heart infusion agar or Sabouraud dextrose agar; and (iii) centrifugation of the suspected organism in a hypertonic solution. There were 176 positive cultures. The centrifugation technique recovered 73% of the positive cultures. The broth and pour plate techniques recovered 38 and 49%, respectively. The centrifugation technique showed an increased isolation rate for Pseudomonas, fungi, and gram-positive cocci. In general, for each organism the time required for the detection of a positive culture was shortest for the centrifugation technique.", "contents": "Blood culture technique based on centrifugation: clinical evaluation. A total of 1,000 blood samples from patients suspected of having a bacteremia were analyzed concurrently, where possible, by three methods: (i) Trypticase soy broth with sodium polyanethol sulfonate and a CO2 atmosphere: (ii) pour plates with either brain heart infusion agar or Sabouraud dextrose agar; and (iii) centrifugation of the suspected organism in a hypertonic solution. There were 176 positive cultures. The centrifugation technique recovered 73% of the positive cultures. The broth and pour plate techniques recovered 38 and 49%, respectively. The centrifugation technique showed an increased isolation rate for Pseudomonas, fungi, and gram-positive cocci. In general, for each organism the time required for the detection of a positive culture was shortest for the centrifugation technique."} {"id": "PMID:1270592", "title": "Clinical comparison of aerobic, hypertonic, and anaerobic culture media for the radiometric detection of bacteremia.", "content": "The BACTEC 225 was used to test 5,811 routine blood cultures over a 20-month period. Aerobic, anaerobic, and hypertonic media were employed. The BACTEC 225 detected 511 positive cultures; 407 of these were considered significant organisms, and 104 were presumed contaminants. Of the significant positive cultures, 15% were detected within the first 12 h of incubation, 52% within 24 h, 82% within 48 h and 92% within 72 h. Aerobic, anaerobic, and hypertonic media are recommended for each venipuncture since 56 cultures were isolated from the aerobic medium only, 110 from the anaerobic medium only, and 94 from the hypertonic medium only. There were 16 patients who had multiple venipunctures from which organisms were repeatedly isolated from only one medium: two from the aerobic medium, four from the anaerobic medium, and ten from the hypertonic medium only. Detection times were not significantly different for the aerobic and hypertonic media. However, there were five patients with multiple venipunctures in which growth was detected radiometrically at least 48 h earlier in the hypertonic than in the aerobic medium. False-positive growth index readings were noted in 1,085 (19%) of the aerobic vial, 11 (0.19%) of the anaerobic vials, microorganisms were isolated from at least one of the companion vials. Using 5% co2 to flush the aerobic vials. With some false-positive aerobic and hypertonic vials decreased the number of false positives to about 6% of the total.", "contents": "Clinical comparison of aerobic, hypertonic, and anaerobic culture media for the radiometric detection of bacteremia. The BACTEC 225 was used to test 5,811 routine blood cultures over a 20-month period. Aerobic, anaerobic, and hypertonic media were employed. The BACTEC 225 detected 511 positive cultures; 407 of these were considered significant organisms, and 104 were presumed contaminants. Of the significant positive cultures, 15% were detected within the first 12 h of incubation, 52% within 24 h, 82% within 48 h and 92% within 72 h. Aerobic, anaerobic, and hypertonic media are recommended for each venipuncture since 56 cultures were isolated from the aerobic medium only, 110 from the anaerobic medium only, and 94 from the hypertonic medium only. There were 16 patients who had multiple venipunctures from which organisms were repeatedly isolated from only one medium: two from the aerobic medium, four from the anaerobic medium, and ten from the hypertonic medium only. Detection times were not significantly different for the aerobic and hypertonic media. However, there were five patients with multiple venipunctures in which growth was detected radiometrically at least 48 h earlier in the hypertonic than in the aerobic medium. False-positive growth index readings were noted in 1,085 (19%) of the aerobic vial, 11 (0.19%) of the anaerobic vials, microorganisms were isolated from at least one of the companion vials. Using 5% co2 to flush the aerobic vials. With some false-positive aerobic and hypertonic vials decreased the number of false positives to about 6% of the total."} {"id": "PMID:1270593", "title": "Evaluation of the API 20 c microtube system for the identification of clinically important yeasts.", "content": "The API 20 C microtube system containing 20 biochemical tests for the identification of yeasts was compared with conventional tests used in the Mayo Clinic mycology laboratory. Three hundred isolates of clinically important yeasts were studied, and agreement of the carbohydrate fermentation and assimilation tests between the systems was good. The API 20 C represents a useful, commercially available screening method for the identification of yeasts; however, it is not a complete system and must be used in conjunction with microscopic morphological features and, when appropriate, with other biochemical tests.", "contents": "Evaluation of the API 20 c microtube system for the identification of clinically important yeasts. The API 20 C microtube system containing 20 biochemical tests for the identification of yeasts was compared with conventional tests used in the Mayo Clinic mycology laboratory. Three hundred isolates of clinically important yeasts were studied, and agreement of the carbohydrate fermentation and assimilation tests between the systems was good. The API 20 C represents a useful, commercially available screening method for the identification of yeasts; however, it is not a complete system and must be used in conjunction with microscopic morphological features and, when appropriate, with other biochemical tests."} {"id": "PMID:1270594", "title": "Anaerobic infections in children: a prospective survey.", "content": "Over an 18-month period, cultures from 95 infants and children yielded 146 anaerobic organisms in 110 clinical specimens. Bacteroides was the most frequently isolated anaerobe, followed by Propionibacterium and Clostridium species. Intra-abdominal sources, soft tissues, and blood were the three major sources (82%) of isolation of anaerobes. Whereas most patients (58%) were over 5 years of age and only 11% were newborns, anaerobic infections constituted a rather uniform proportion of all infections, regardless of sources, in all age groups. Anaerobes accounted for only 2.9% of all positive cultures encountered from the various sources. Rates of recovery of anaerobes from intra-abdominal sources were significantly the highest, and from soft-tissue infections they were significantly the lowest. The anaerobic bacteremias observed were of no clinical significance when Propionibacterium species were isolated; however, recovery of other anaerobes from the blood, and primarily Bacteroides species, was usually associated with clinical disease. Except in blood cultures, anaerobes almost invariably coexisted with facultative bacteria.", "contents": "Anaerobic infections in children: a prospective survey. Over an 18-month period, cultures from 95 infants and children yielded 146 anaerobic organisms in 110 clinical specimens. Bacteroides was the most frequently isolated anaerobe, followed by Propionibacterium and Clostridium species. Intra-abdominal sources, soft tissues, and blood were the three major sources (82%) of isolation of anaerobes. Whereas most patients (58%) were over 5 years of age and only 11% were newborns, anaerobic infections constituted a rather uniform proportion of all infections, regardless of sources, in all age groups. Anaerobes accounted for only 2.9% of all positive cultures encountered from the various sources. Rates of recovery of anaerobes from intra-abdominal sources were significantly the highest, and from soft-tissue infections they were significantly the lowest. The anaerobic bacteremias observed were of no clinical significance when Propionibacterium species were isolated; however, recovery of other anaerobes from the blood, and primarily Bacteroides species, was usually associated with clinical disease. Except in blood cultures, anaerobes almost invariably coexisted with facultative bacteria."} {"id": "PMID:1270595", "title": "Gingival flora of the dog with special reference to bacteria associated with bites.", "content": "Gingival scrapings from dogs were examined to determine their aerobic bacterial flora. Of particular interest was the frequent recovery of three unclassified groups of aerobic gram-negative bacteria, IIj, EF-4, and M-5, previously associated with human dog-bite infections. Although no set pattern was found between the variability and consistency of gingival microbiota as related to age, sex, or breed of dog, a certain characteristic flora can be predicted in the healthy canine gingiva. Members of the following genera were found: Streptococcus, Staphylococcus, Actinomyces, Escherichia, Corynebacterium, Pasteurella, Caryophanon, Mycoplasma, Acinetobacter, Moraxella, Neisseria, Enterobacter, and Bacillus.", "contents": "Gingival flora of the dog with special reference to bacteria associated with bites. Gingival scrapings from dogs were examined to determine their aerobic bacterial flora. Of particular interest was the frequent recovery of three unclassified groups of aerobic gram-negative bacteria, IIj, EF-4, and M-5, previously associated with human dog-bite infections. Although no set pattern was found between the variability and consistency of gingival microbiota as related to age, sex, or breed of dog, a certain characteristic flora can be predicted in the healthy canine gingiva. Members of the following genera were found: Streptococcus, Staphylococcus, Actinomyces, Escherichia, Corynebacterium, Pasteurella, Caryophanon, Mycoplasma, Acinetobacter, Moraxella, Neisseria, Enterobacter, and Bacillus."} {"id": "PMID:1270596", "title": "Inhibition of Bacteroides fragilis on blood agar plates and reversal of inhibition by added hemin.", "content": "Bacteroides fragilis strains formed much smaller colonies on most types of blood agar plates than they did on the same media without blood. Blood inhibited strains of B. fragilis subsp. distasonis the most and B. fragilis subsp. fragilis the least. The inhibition could be eliminated by adding hemin to the blood agar. The inhibitory component of the blood was inside the erythrocytes and appeared to be the hemin-free globin of hemoglobin.", "contents": "Inhibition of Bacteroides fragilis on blood agar plates and reversal of inhibition by added hemin. Bacteroides fragilis strains formed much smaller colonies on most types of blood agar plates than they did on the same media without blood. Blood inhibited strains of B. fragilis subsp. distasonis the most and B. fragilis subsp. fragilis the least. The inhibition could be eliminated by adding hemin to the blood agar. The inhibitory component of the blood was inside the erythrocytes and appeared to be the hemin-free globin of hemoglobin."} {"id": "PMID:1270597", "title": "Inhibition of Streptococcus mutans strains by different mitis-salivarius agar preparations.", "content": "Several Streptococcus mutans strains were markedly inhibited by mitis-salivarius agar manufactured by Baltimore Biological Laboratories, but little, if any, inhibition was noted using Difco Laboratories' mitis-salivarius agar. Supplementation of the basic medium with sucrose and bacitracin for specific selection of S. mutans resulted in suppression of representative S. mutans type a strains regardless of manufacturer.", "contents": "Inhibition of Streptococcus mutans strains by different mitis-salivarius agar preparations. Several Streptococcus mutans strains were markedly inhibited by mitis-salivarius agar manufactured by Baltimore Biological Laboratories, but little, if any, inhibition was noted using Difco Laboratories' mitis-salivarius agar. Supplementation of the basic medium with sucrose and bacitracin for specific selection of S. mutans resulted in suppression of representative S. mutans type a strains regardless of manufacturer."} {"id": "PMID:1270598", "title": "Pitting of agar surface by Pseudomonas stutzeri.", "content": "A strain of Pseudomonas stutzeri which exhibited pitting of agar surfaces is described.", "contents": "Pitting of agar surface by Pseudomonas stutzeri. A strain of Pseudomonas stutzeri which exhibited pitting of agar surfaces is described."} {"id": "PMID:1270599", "title": "Dependability of sensitivity tests in primary culture.", "content": "Primary sensitivity tests were done on 90 specimens of infected urine, and the results were compared with those of secondary tests on pure cultures done by three diffusion methods. There was good correlation between the four methods. In a second study, the reliability of primary tests prepared in the clinical laboratory on specimens of pus was assessed, and the frequency with which a definitive result was obtained with different types of specimen was determined. Recommendations are made for the economic use of these tests.", "contents": "Dependability of sensitivity tests in primary culture. Primary sensitivity tests were done on 90 specimens of infected urine, and the results were compared with those of secondary tests on pure cultures done by three diffusion methods. There was good correlation between the four methods. In a second study, the reliability of primary tests prepared in the clinical laboratory on specimens of pus was assessed, and the frequency with which a definitive result was obtained with different types of specimen was determined. Recommendations are made for the economic use of these tests."} {"id": "PMID:1270600", "title": "Counter-immunoelectro-osmophoresis for the detection of infantile gastroenteritis virus (orbi-group) antigen and antibody.", "content": "A moderatley sensitive, rapid, and economical test scheme for the detection of infantile gastroenteritis virus (IGV) in stool or antibody in serum has been developed and evaluated. The test scheme with minor modifications was an adaptation of a counter-immunoelectro-osmophoresis system we once used for the detection of hepatitis B antigen. Large numbers of stool samples may be screened during half a working day for the presence of IGV using reference antiserum to IGV prepared in guinea-pigs. Serological studies of a diagnostic but not epidemiological nature may also be performed with equal facility by this same test scheme using highly purified IGV antigen derived from stool.", "contents": "Counter-immunoelectro-osmophoresis for the detection of infantile gastroenteritis virus (orbi-group) antigen and antibody. A moderatley sensitive, rapid, and economical test scheme for the detection of infantile gastroenteritis virus (IGV) in stool or antibody in serum has been developed and evaluated. The test scheme with minor modifications was an adaptation of a counter-immunoelectro-osmophoresis system we once used for the detection of hepatitis B antigen. Large numbers of stool samples may be screened during half a working day for the presence of IGV using reference antiserum to IGV prepared in guinea-pigs. Serological studies of a diagnostic but not epidemiological nature may also be performed with equal facility by this same test scheme using highly purified IGV antigen derived from stool."} {"id": "PMID:1270601", "title": "A card test for the serodiagnosis of human leptospirosis.", "content": "A macroscopic agglutination test for detecting leptospiral antibodies in human sera is described. The test utilizes a stained preparation of non-pathogenic leptospires and is performed on the Brewer diagnostic cards used for bovine brucellosis screening. The agglutination of the stained antigen is more easily observed than the current macroscopic slide test using unstained leptospiral antigens. The non-pathogenic serotype patoc is agglutinated by sera from humans infected with serotypes pomona, hardjo, ballum, and copenhageni with a sensitivity of 94% in comparison with the microscopic agglutination test.", "contents": "A card test for the serodiagnosis of human leptospirosis. A macroscopic agglutination test for detecting leptospiral antibodies in human sera is described. The test utilizes a stained preparation of non-pathogenic leptospires and is performed on the Brewer diagnostic cards used for bovine brucellosis screening. The agglutination of the stained antigen is more easily observed than the current macroscopic slide test using unstained leptospiral antigens. The non-pathogenic serotype patoc is agglutinated by sera from humans infected with serotypes pomona, hardjo, ballum, and copenhageni with a sensitivity of 94% in comparison with the microscopic agglutination test."} {"id": "PMID:1270602", "title": "Idiopathic non-syphilitic paroxysmal cold haemoglobinuria in children.", "content": "Three examples of non-syphilitic paroxysmal cold haemoglobinuria (PCH) in children are described which occurred, within a period of 16 days, in association with a febrile illness. No definite viral aetiology or obvious epidemiological association could be established. A Donath-Landsteiner antibody of anti-P specificity was demonstrated in all three patients. The serological aspects of PCH are critically discussed.", "contents": "Idiopathic non-syphilitic paroxysmal cold haemoglobinuria in children. Three examples of non-syphilitic paroxysmal cold haemoglobinuria (PCH) in children are described which occurred, within a period of 16 days, in association with a febrile illness. No definite viral aetiology or obvious epidemiological association could be established. A Donath-Landsteiner antibody of anti-P specificity was demonstrated in all three patients. The serological aspects of PCH are critically discussed."} {"id": "PMID:1270603", "title": "Chemotaxis, random mobility, and mobilization of polymorphonuclear leucocytes in malnutrition.", "content": "Neutrophil mobilization following administration of Pseudomonas polysaccharide was significantly reduced in malnutrition, especially during infection. The random mobility of polymorphonuclear leucocytes (PMNs) was slightly decreased in undernutrition. Chemotactic migration of PMNs was depressed and correlated more with the presence of infection than with nutritional deficiency. It is possible that these abnormalities of PMN mobilization and mobility in malnourished individuals contribute to suboptimal amount, kinetics, and pattern of tissue inflammatory response to bacteraemic challenge.", "contents": "Chemotaxis, random mobility, and mobilization of polymorphonuclear leucocytes in malnutrition. Neutrophil mobilization following administration of Pseudomonas polysaccharide was significantly reduced in malnutrition, especially during infection. The random mobility of polymorphonuclear leucocytes (PMNs) was slightly decreased in undernutrition. Chemotactic migration of PMNs was depressed and correlated more with the presence of infection than with nutritional deficiency. It is possible that these abnormalities of PMN mobilization and mobility in malnourished individuals contribute to suboptimal amount, kinetics, and pattern of tissue inflammatory response to bacteraemic challenge."} {"id": "PMID:1270604", "title": "The 'septic spleen'--a critical evaluation.", "content": "The relationship between the consistency of the spleen at necropsy and the presence of bacteria in that organ was examined in 192 consecutive necropsies. Also it was noted if the patient had received antibiotics just before death. An estimate of the number of neutrophils in the spleen was also made. No correlation could be found between any of these factors.", "contents": "The 'septic spleen'--a critical evaluation. The relationship between the consistency of the spleen at necropsy and the presence of bacteria in that organ was examined in 192 consecutive necropsies. Also it was noted if the patient had received antibiotics just before death. An estimate of the number of neutrophils in the spleen was also made. No correlation could be found between any of these factors."} {"id": "PMID:1270605", "title": "Liver-originating isoenzymes of alkaline phosphatase in the serum: a paraneoplastic manifestation of a malignant schwannoma of the sciatic nerve.", "content": "A case of malignant schwannoma of the sciatic nerve is described associated with hepatic dysfunction in the absence of hepatic metastases. An elevated serum alkaline phosphatase activity was present with an isoenzyme pattern indicating hepatic involvement. These abnormalities disappeared after extirpation of the tumour. The patient is well, with no evidence of metastases, over two years later. It is concluded that the abnormality of serum alkaline phosphatase was induced by the tumour, and that the liver can be involved in the paraneoplastic syndrome.", "contents": "Liver-originating isoenzymes of alkaline phosphatase in the serum: a paraneoplastic manifestation of a malignant schwannoma of the sciatic nerve. A case of malignant schwannoma of the sciatic nerve is described associated with hepatic dysfunction in the absence of hepatic metastases. An elevated serum alkaline phosphatase activity was present with an isoenzyme pattern indicating hepatic involvement. These abnormalities disappeared after extirpation of the tumour. The patient is well, with no evidence of metastases, over two years later. It is concluded that the abnormality of serum alkaline phosphatase was induced by the tumour, and that the liver can be involved in the paraneoplastic syndrome."} {"id": "PMID:1270606", "title": "Colonic lymphoid-glandular complex (microbursa): nature and morphology.", "content": "A study of lymphoid-glandular complexes of the large bowel has been undertaken. Sections from 1924 surgical colectomy and proctocolectomy specimens were examined, and lymphoid-glandular complexes were observed in 231. It has been shown that they are distributed throughout the large bowel and occur in all age groups and in normal and disease states. An analogy has been drawn between them, the palatine tonsils, and the bursa of Fabricius. It is concluded that the lymphoid-glandular complex is, most probably, a normal structural entity of the large bowel and that it acts as a local receptor of antigenic material for future immune recognition. It is suggested that microbursa rather than lymphoid-glandular complex is more apt name for this structure.", "contents": "Colonic lymphoid-glandular complex (microbursa): nature and morphology. A study of lymphoid-glandular complexes of the large bowel has been undertaken. Sections from 1924 surgical colectomy and proctocolectomy specimens were examined, and lymphoid-glandular complexes were observed in 231. It has been shown that they are distributed throughout the large bowel and occur in all age groups and in normal and disease states. An analogy has been drawn between them, the palatine tonsils, and the bursa of Fabricius. It is concluded that the lymphoid-glandular complex is, most probably, a normal structural entity of the large bowel and that it acts as a local receptor of antigenic material for future immune recognition. It is suggested that microbursa rather than lymphoid-glandular complex is more apt name for this structure."} {"id": "PMID:1270607", "title": "Sputum cytology in two cases of Wegener's granulomatosis.", "content": "Two patients with Wegener's granulomatosis are described in whom the sputum was found to contain abnormal cells, The diagnosis was suggested in the second case on cytological grounds alone. It is considered, therefore, that sputum cytology is a relevant investigation in the diagnosis of this condition.", "contents": "Sputum cytology in two cases of Wegener's granulomatosis. Two patients with Wegener's granulomatosis are described in whom the sputum was found to contain abnormal cells, The diagnosis was suggested in the second case on cytological grounds alone. It is considered, therefore, that sputum cytology is a relevant investigation in the diagnosis of this condition."} {"id": "PMID:1270608", "title": "A modification of Hepatest, using the Terasaki plate, for the detection of HBSAg in blood donors.", "content": "A simple modification of Hepatest (Wellcome Reagents) is described, which lends itself to the rapid large-scale screening of blood donors. The technique uses 4 mul of HBSAb coated turkey cells (Cayzer et al., 1974), and Terasaki plates (Hopkins and Das, 1973), in contrast to the 25 mul used in the microtitre tray technique. This results in a considerable saving on the cost of reagents, the cost per test being reduced to 16% of the cost of the recommended method. In our hands, this modification is as convenient to use as the manual microtitre tray technique. Positive sera from the screen test are also tested for non-specificity using horse IgG coated turkey control cells. The falso positive screen test rate has been reduced by the adoption of a modified buffer containing turkey serum.", "contents": "A modification of Hepatest, using the Terasaki plate, for the detection of HBSAg in blood donors. A simple modification of Hepatest (Wellcome Reagents) is described, which lends itself to the rapid large-scale screening of blood donors. The technique uses 4 mul of HBSAb coated turkey cells (Cayzer et al., 1974), and Terasaki plates (Hopkins and Das, 1973), in contrast to the 25 mul used in the microtitre tray technique. This results in a considerable saving on the cost of reagents, the cost per test being reduced to 16% of the cost of the recommended method. In our hands, this modification is as convenient to use as the manual microtitre tray technique. Positive sera from the screen test are also tested for non-specificity using horse IgG coated turkey control cells. The falso positive screen test rate has been reduced by the adoption of a modified buffer containing turkey serum."} {"id": "PMID:1270609", "title": "Projections of the locus coeruleus and adjacent pontine tegmentum in the cat.", "content": "The projections of the locus coeruleus and adjacent pontine tegmentum have been studied using anatomical and physiological methods in the cat. Axonal trajectories were traced using either the Fink-Heimer I method following electrolytic lesions, or the autoradiographic method after injection of tritiated proline into the nucleus. Results with both methods were similar. Axons of locus noeruleus neurons ascended ipsilaterally through the mesencephalon lateral to the medial longitudinal fasiculus, ventrolateral to the central gray. In the caudal diencephalon, the ascending fibers entered the centrum medianum-parafascicular complex where they diverged into two fascicles: a dorsal fascicle which terminated in the intralaminar nuclei of the thalamus, and a ventral fascicle which gave off fibers to the ventrobasal complex and reticular nucleus of the thalamus while continuing centrolaterally into the lateral hypothalamus medial to the internal capsule. Fibers of the ventral fascicle ascended in the lateral hypothalamus and zona incerta and were traced through the preoptic region into the septum. Fibers could not be consistently traced to the cerebral cortex, and were not seen at all in the cerebellum. Throughout the ascending course of the path from the locus coeruleus, axons were given off to the pretectal area, the medial and lateral geniculate nuclei and the amygdala; fibers passed contralaterally through the posterior commissure, the midline thalamus, and the supraoptic commissure. Fibers descending from the locus coeruleus surrounded the intramedullary portion of the facial nerve and further caudally were observed ventrolateral to the hypoglossal and dorsal vagal nuclei. The axonal trajectories visualized with degeneration and autoradiographic methods followed closely those previously shown for reticular formation neurons, but were also similar to locus coeruleus projections revealed by histofluorescence methods. After injections of horseradish peroxidase into the centrum medianum-parafascicular complex, lateral hypothalamus or preoptic region, labeled neurons were located in the locus coeruleus, nucleus subcoeruleus, and lateral parabrachial nucleus. Reticular formation neurons were not labeled. Neurons in locus coeruleus and adjacent pontine tegmentum could be antidromically activated by stimulation in the rostral midbrain or caudal diencephalon. Our data indicate that both adrenergic and non-adrenergic neurons of the dorsolateral pontine tegmentum have similar projections.", "contents": "Projections of the locus coeruleus and adjacent pontine tegmentum in the cat. The projections of the locus coeruleus and adjacent pontine tegmentum have been studied using anatomical and physiological methods in the cat. Axonal trajectories were traced using either the Fink-Heimer I method following electrolytic lesions, or the autoradiographic method after injection of tritiated proline into the nucleus. Results with both methods were similar. Axons of locus noeruleus neurons ascended ipsilaterally through the mesencephalon lateral to the medial longitudinal fasiculus, ventrolateral to the central gray. In the caudal diencephalon, the ascending fibers entered the centrum medianum-parafascicular complex where they diverged into two fascicles: a dorsal fascicle which terminated in the intralaminar nuclei of the thalamus, and a ventral fascicle which gave off fibers to the ventrobasal complex and reticular nucleus of the thalamus while continuing centrolaterally into the lateral hypothalamus medial to the internal capsule. Fibers of the ventral fascicle ascended in the lateral hypothalamus and zona incerta and were traced through the preoptic region into the septum. Fibers could not be consistently traced to the cerebral cortex, and were not seen at all in the cerebellum. Throughout the ascending course of the path from the locus coeruleus, axons were given off to the pretectal area, the medial and lateral geniculate nuclei and the amygdala; fibers passed contralaterally through the posterior commissure, the midline thalamus, and the supraoptic commissure. Fibers descending from the locus coeruleus surrounded the intramedullary portion of the facial nerve and further caudally were observed ventrolateral to the hypoglossal and dorsal vagal nuclei. The axonal trajectories visualized with degeneration and autoradiographic methods followed closely those previously shown for reticular formation neurons, but were also similar to locus coeruleus projections revealed by histofluorescence methods. After injections of horseradish peroxidase into the centrum medianum-parafascicular complex, lateral hypothalamus or preoptic region, labeled neurons were located in the locus coeruleus, nucleus subcoeruleus, and lateral parabrachial nucleus. Reticular formation neurons were not labeled. Neurons in locus coeruleus and adjacent pontine tegmentum could be antidromically activated by stimulation in the rostral midbrain or caudal diencephalon. Our data indicate that both adrenergic and non-adrenergic neurons of the dorsolateral pontine tegmentum have similar projections."} {"id": "PMID:1270610", "title": "Topological analysis of the brain stem of the axolotl Ambystoma mexicanum.", "content": "The ventricular sulcal pattern and the cellular structure of the brain stem of the axolotl Ambystoma mexicanum have been studied in transversely cut Nissl and Bodian stained serial sections. Six longitudinal sulci, the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans, the sulcus intermedius dorsalis, the sulcus medianus superior and the sulcus lateralis mesencephali could be distinguished. A seventh groove, the sulcus isthmi, clearly deviates from the overall longitudinal pattern of the other sulci. Although most neuronal perikarya are contained within a diffuse periventricular gray, 19 cell masses could be delineated; seven of these are primary efferent or motor nuclei, four are primary afferent or sensory centers, four nuclei are considered as components of the reticular formation, and the remaining four cell masses can be interpreted as \"relay\" nuclei. In order to study the zonal pattern of the brain stem, this structure was subjected to a topological analysis (cf, Nieuwenhuys, '74 and fig. 13). This analysis yielded the following results. In the rhombencephalon the grisea are arranged in four longitudinal zones which, following Kuhlenbeck, have been termed area ventralis, area intermedioventralis, area intermediodorsalis and area dorsalis. Where present the sulcus intermedius ventralis, the sulcus limitans and the sulcus intermedius dorsalis mark the boundaries between these four morphological entities. The zonal areas in question coincide largely, but not entirely, with the so-called functional columns of Herrick and Johnston. The most obvious incongruity is that the area intermediodorsalis contains, in addition to the nucleus fasciculi solitarii and the nucleus visceralis secundarius, two non-visceral sensory cell masses, namely the nucleus vestibularis magnocellularis and the nucleus cerebelli. The four morphological zones delineated in the rhombencephalon cannot be distinguished in the mesencephalon and it is of particular importance that the sulcus limitans does not extend into this part of the brain. Functionally, however, the medial part of the tegmentum mesencephali may be considered the rostral extreme of the somatic motor column, whereas the tectum primarily represents a somatic sensory correlation area.", "contents": "Topological analysis of the brain stem of the axolotl Ambystoma mexicanum. The ventricular sulcal pattern and the cellular structure of the brain stem of the axolotl Ambystoma mexicanum have been studied in transversely cut Nissl and Bodian stained serial sections. Six longitudinal sulci, the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans, the sulcus intermedius dorsalis, the sulcus medianus superior and the sulcus lateralis mesencephali could be distinguished. A seventh groove, the sulcus isthmi, clearly deviates from the overall longitudinal pattern of the other sulci. Although most neuronal perikarya are contained within a diffuse periventricular gray, 19 cell masses could be delineated; seven of these are primary efferent or motor nuclei, four are primary afferent or sensory centers, four nuclei are considered as components of the reticular formation, and the remaining four cell masses can be interpreted as \"relay\" nuclei. In order to study the zonal pattern of the brain stem, this structure was subjected to a topological analysis (cf, Nieuwenhuys, '74 and fig. 13). This analysis yielded the following results. In the rhombencephalon the grisea are arranged in four longitudinal zones which, following Kuhlenbeck, have been termed area ventralis, area intermedioventralis, area intermediodorsalis and area dorsalis. Where present the sulcus intermedius ventralis, the sulcus limitans and the sulcus intermedius dorsalis mark the boundaries between these four morphological entities. The zonal areas in question coincide largely, but not entirely, with the so-called functional columns of Herrick and Johnston. The most obvious incongruity is that the area intermediodorsalis contains, in addition to the nucleus fasciculi solitarii and the nucleus visceralis secundarius, two non-visceral sensory cell masses, namely the nucleus vestibularis magnocellularis and the nucleus cerebelli. The four morphological zones delineated in the rhombencephalon cannot be distinguished in the mesencephalon and it is of particular importance that the sulcus limitans does not extend into this part of the brain. Functionally, however, the medial part of the tegmentum mesencephali may be considered the rostral extreme of the somatic motor column, whereas the tectum primarily represents a somatic sensory correlation area."} {"id": "PMID:1270612", "title": "The synaptic cluster (glomerulus) in the inferior olivary nucleus.", "content": "This report describes the fine structural features and distribution of the synaptic cluster (glomerulus) within the inferior olivary nucleus of the opossum. The postsynaptic elements typically include spiny appendages and small diameter dendrites which exhibit attachment plaques and gap junctions. Profiles presynaptic to the central core of postsynaptic elements were differentiated on the basis of vesicle shape, vesicle size, as measured by a computer system, and junctional characteristics. Three categories of terminals with clear vesicles are present within the synaptic clusters in all nuclear divisions of the olive, whereas a fourth with large dense core vesicles is restricted primarily to the principal nucleus. The groups of pre and postsynaptic elements are surrounded by astrocytic lamellae and are most frequently encountered in the principal and rostral portions of the medial accessory nuclei. Possible identification of the sources of the synaptic components is discussed in relation to data available from Golgi impregnations, physiological reports and hodological evidence.", "contents": "The synaptic cluster (glomerulus) in the inferior olivary nucleus. This report describes the fine structural features and distribution of the synaptic cluster (glomerulus) within the inferior olivary nucleus of the opossum. The postsynaptic elements typically include spiny appendages and small diameter dendrites which exhibit attachment plaques and gap junctions. Profiles presynaptic to the central core of postsynaptic elements were differentiated on the basis of vesicle shape, vesicle size, as measured by a computer system, and junctional characteristics. Three categories of terminals with clear vesicles are present within the synaptic clusters in all nuclear divisions of the olive, whereas a fourth with large dense core vesicles is restricted primarily to the principal nucleus. The groups of pre and postsynaptic elements are surrounded by astrocytic lamellae and are most frequently encountered in the principal and rostral portions of the medial accessory nuclei. Possible identification of the sources of the synaptic components is discussed in relation to data available from Golgi impregnations, physiological reports and hodological evidence."} {"id": "PMID:1270613", "title": "Auditory cortex in the grey squirrel: tonotopic organization and architectonic fields.", "content": "The representation of sound frequency within auditory cortex has been investigated with microelectrode mapping techniques in grey squirrels. The cyto- and myeloarchitecture of mapped cortical surfaces was examined and related to recording data. Among the results were the following: (1) A primary field can be defined on the basis of both physiological and anatomical criteria.", "contents": "Auditory cortex in the grey squirrel: tonotopic organization and architectonic fields. The representation of sound frequency within auditory cortex has been investigated with microelectrode mapping techniques in grey squirrels. The cyto- and myeloarchitecture of mapped cortical surfaces was examined and related to recording data. Among the results were the following: (1) A primary field can be defined on the basis of both physiological and anatomical criteria."} {"id": "PMID:1270614", "title": "Convergent thalamic and mesencephalic projections to the anterior medial cortex in the rat.", "content": "Small microelectrophoretic deposits of horseradish-peroxidase (HRP) were placed at various loci within the gray matter of the rat's anterior medial cortex. A comparison of the patterns of retrograde cell-labeling charted in 26 such cases confirmed earlier findings in fiber-degeneration studies according to which the respective thalamocortical projections of the mediodorsal (MD) and anteromedial nucleus (AM) overlap each other over a wide region of the anterior medial cortex. This region of thalamocortical convergence, extending from pregenual levels caudalward as far as the anterior border of the retrosplenial cortex, corresponds almost exactly to the cortical region from which locally deposited HRP was found to be transported so as to label cells in one or both of two mesencephalic cell groups: the ventral tegmental area (AVT) dorsal and lateral to the interpeduncular nucleus, and the medial one-quarter of the pars compacta of the substantia nigra (SNC).", "contents": "Convergent thalamic and mesencephalic projections to the anterior medial cortex in the rat. Small microelectrophoretic deposits of horseradish-peroxidase (HRP) were placed at various loci within the gray matter of the rat's anterior medial cortex. A comparison of the patterns of retrograde cell-labeling charted in 26 such cases confirmed earlier findings in fiber-degeneration studies according to which the respective thalamocortical projections of the mediodorsal (MD) and anteromedial nucleus (AM) overlap each other over a wide region of the anterior medial cortex. This region of thalamocortical convergence, extending from pregenual levels caudalward as far as the anterior border of the retrosplenial cortex, corresponds almost exactly to the cortical region from which locally deposited HRP was found to be transported so as to label cells in one or both of two mesencephalic cell groups: the ventral tegmental area (AVT) dorsal and lateral to the interpeduncular nucleus, and the medial one-quarter of the pars compacta of the substantia nigra (SNC)."} {"id": "PMID:1270615", "title": "The olivocerebellar projection in the cat as studied with the method of retrograde axonal transport of horseradish peroxidase. II. The projection to the uvula.", "content": "Following injections of small quantities of horseradish peroxidase (HRP) suspension in the uvula of the cat, the distribution of labeled cells in the inferior olive has been mapped. The findings confirm the conclusion made on the basis of studies of retrograde cell loss in the olive following ablations of the uvula (Brodal, '40b) that two small olivary subdivisions, the nucleus beta and the dorsomedial cell column project heavily to the uvula. In addition the HRP-study shows that the uvula receives a smaller number of fibers from two circumscribed areas of the contralateral medial accessory olive. These areas appear to project to the lateralmost parts of the uvula (fig. 4). The findings thus support the presence of a longitudinal zonal subdivision in the uvula. Labeled cells are found in the nucleus beta and the dorsomedial cell column also following injections of the fastigial nucleus and to a lesser degree of lobulus VII of the vermis (Hoddevik et al. 76). This may be due to collateral branching of olivary efferents. There is some evidence for a topographical correlation between dorsal and ventral parts of the uvula and rostral and caudal parts, respectively, of the nucleus beta and the dorsomedial cell column. This may be related to functional differences between the two parts of the uvula.", "contents": "The olivocerebellar projection in the cat as studied with the method of retrograde axonal transport of horseradish peroxidase. II. The projection to the uvula. Following injections of small quantities of horseradish peroxidase (HRP) suspension in the uvula of the cat, the distribution of labeled cells in the inferior olive has been mapped. The findings confirm the conclusion made on the basis of studies of retrograde cell loss in the olive following ablations of the uvula (Brodal, '40b) that two small olivary subdivisions, the nucleus beta and the dorsomedial cell column project heavily to the uvula. In addition the HRP-study shows that the uvula receives a smaller number of fibers from two circumscribed areas of the contralateral medial accessory olive. These areas appear to project to the lateralmost parts of the uvula (fig. 4). The findings thus support the presence of a longitudinal zonal subdivision in the uvula. Labeled cells are found in the nucleus beta and the dorsomedial cell column also following injections of the fastigial nucleus and to a lesser degree of lobulus VII of the vermis (Hoddevik et al. 76). This may be due to collateral branching of olivary efferents. There is some evidence for a topographical correlation between dorsal and ventral parts of the uvula and rostral and caudal parts, respectively, of the nucleus beta and the dorsomedial cell column. This may be related to functional differences between the two parts of the uvula."} {"id": "PMID:1270616", "title": "Retinogeniculate projections in albino and ocularly hypopigmented rats.", "content": "The retinogeniculate fiber projections were studied by degeneration methods in several strains of rats with pigmentation in their eyes and pelts ranging from the intensely pigmented self phenotype to the albino. The ipsilateral retinogeniculate input in the self, Irish, and hooded rats, and rats with \"bicolor fundus\" is located medially within the dorsal alteral geniculate nucleus (LGd) and is seen as a single lamina of moderately dense degeneration.", "contents": "Retinogeniculate projections in albino and ocularly hypopigmented rats. The retinogeniculate fiber projections were studied by degeneration methods in several strains of rats with pigmentation in their eyes and pelts ranging from the intensely pigmented self phenotype to the albino. The ipsilateral retinogeniculate input in the self, Irish, and hooded rats, and rats with \"bicolor fundus\" is located medially within the dorsal alteral geniculate nucleus (LGd) and is seen as a single lamina of moderately dense degeneration."} {"id": "PMID:1270617", "title": "Fiber analysis of the feline inferior cardiac sympathetic nerve.", "content": "The left inferior cardiac nerves of nine adult cats were examined with the electron microscope. Electrical recordings were also made from four of these nerves. Most of the nerves contained between 25,000 and 40,000 unmyelinated fibers and 30 to 150 myelinated fibers. The diameters of the unmyelinated fibers ranged from 0.1 mu to 1.8 mu with mean diameters ranging from 0.47 to 0.78 mu in the various nerves. The myelinated fibers ranged in diameter from 1 mu to 9 mu with a mean difference of approximately 3 mu. Electrical recordings showed two peaks in both the C fiber and the Adelta fiber compound action potentials. Conduction velocities of the two C fiber peaks were approximately 0.7 and 0.9 m/sec. The two groups of A delta fibers had conduction velocities of approximately 7 and 16 m/sec.", "contents": "Fiber analysis of the feline inferior cardiac sympathetic nerve. The left inferior cardiac nerves of nine adult cats were examined with the electron microscope. Electrical recordings were also made from four of these nerves. Most of the nerves contained between 25,000 and 40,000 unmyelinated fibers and 30 to 150 myelinated fibers. The diameters of the unmyelinated fibers ranged from 0.1 mu to 1.8 mu with mean diameters ranging from 0.47 to 0.78 mu in the various nerves. The myelinated fibers ranged in diameter from 1 mu to 9 mu with a mean difference of approximately 3 mu. Electrical recordings showed two peaks in both the C fiber and the Adelta fiber compound action potentials. Conduction velocities of the two C fiber peaks were approximately 0.7 and 0.9 m/sec. The two groups of A delta fibers had conduction velocities of approximately 7 and 16 m/sec."} {"id": "PMID:1270618", "title": "Organization and development of brain stem auditory nuclei of the chicken: ontogeny of n. magnocellularis and n. laminaris.", "content": "Nucleus magnocellularis (NM) and nucleus laminaris (NL) are, respectively, second- and third-order auditory nuclei in the chicken brain stem. In this report the morphogenesis of these nuclei is examined. The times of origin of the cells of these nuclei were studied with 3H-thymidine autoradiography. The number of cells in each nucleus and their rostro-caudal distribution within each nucleus was determined in Nissl-stained sections at 9, 11, 13, 15, 17, 19, and 21 days of incubation. For the above ages the volumes of NM and NL were also calculated planimetrically and the rostro-caudal distribution of volume within each nucleus was studied.", "contents": "Organization and development of brain stem auditory nuclei of the chicken: ontogeny of n. magnocellularis and n. laminaris. Nucleus magnocellularis (NM) and nucleus laminaris (NL) are, respectively, second- and third-order auditory nuclei in the chicken brain stem. In this report the morphogenesis of these nuclei is examined. The times of origin of the cells of these nuclei were studied with 3H-thymidine autoradiography. The number of cells in each nucleus and their rostro-caudal distribution within each nucleus was determined in Nissl-stained sections at 9, 11, 13, 15, 17, 19, and 21 days of incubation. For the above ages the volumes of NM and NL were also calculated planimetrically and the rostro-caudal distribution of volume within each nucleus was studied."} {"id": "PMID:1270619", "title": "Pallidothalamic projections in the rat.", "content": "The purpose of this investigation was to examine pallidofugal projections to the thalamus of the rat using a selective silver degeneration method and autoradiography. Degenerating pallidothalamic projections emerging from the anterior part of the pallidum formed two diffuse groups of fibers; one coursed ventromedially directly through the internal capsule without forming a lenticular fasciculus and terminated uniformly in the reticular, VA, VD, VM and the medial part of the VE. The otehr group coursed ventrolaterally in the internal capsule and, without forming an ansa lenticularis, entered the zona incerta, swept medially through and ventral to the medial lemniscus, and terminated in the medial part of the VE and throughout the VD.", "contents": "Pallidothalamic projections in the rat. The purpose of this investigation was to examine pallidofugal projections to the thalamus of the rat using a selective silver degeneration method and autoradiography. Degenerating pallidothalamic projections emerging from the anterior part of the pallidum formed two diffuse groups of fibers; one coursed ventromedially directly through the internal capsule without forming a lenticular fasciculus and terminated uniformly in the reticular, VA, VD, VM and the medial part of the VE. The otehr group coursed ventrolaterally in the internal capsule and, without forming an ansa lenticularis, entered the zona incerta, swept medially through and ventral to the medial lemniscus, and terminated in the medial part of the VE and throughout the VD."} {"id": "PMID:1270620", "title": "Trans-glial channels in ventral nerve roots of crayfish.", "content": "The sheath around the roots of the sixth abdominal ganglion in the ventral nerve cord of the crayfish consists of concentric layers of thin glial processes alternating with wide clefts containing filamentous connective tissue. Regions of each glial lamella are perforated by single, short, tubular channels: the trans-glial channels. In thin plastic sections examined in the electron microscope, the channels appear as slits that are 240 A wide and 450-550 A long which traverse glial lamellae less than 1,500 A thick. Branched tubular channels cross glial sheets that are thicker than 1,500 A. The thickest glial wrap is adaxonal; it closely encapsulates individual axons and its cell membrane is separated from the axolemma by a collagen-free space of only 150 A. The adaxonal glial cytoplasm contains unique, three-dimensional networks of interconnected tubules. Separate tubular lattices occur along these thicker processes. In replicas of freeze-fractured sheaths, the outer half of the plasma membrane belonging to the thin glial sheets exhibits many volcano-like protrusions which represent cross fractures through the necks of trans-glial channels. Corresponding depressions on the inner half of these membranes are sites where the plasma membrane invaginates to form the channels. Although some channels are randomly dispersed, others are lineraly positioned in restricted areas across successive glial layers. The number of channels is far more readily appreciated in replicas than in thin sections. The average frequency of channels is 16 per mu2 (range 8 to 33) in normal roots and does not differ significantly from the average of 13 per mu2 in proximal stumps of roots fixed three to four weeks after the roots were cut. The channels are not precisely aligned from one glial layer to the next but do appear to coincide approximately with the adaxonal tubular lattice. The combination of trans-glial channels and adaxonal tubular lattices may provide a complex conduit that could facilitate a rapid, passive flow of electrolytes and nutrients across the nerve sheath to the axonal surface. Horseradish peroxidase solutions bathing the ventral roots enter the trans-glial channels, extracellular clefts and finally the tubular lattices. This distribution supports the proposed role of the channels in a rapid extracellular passage of solutes. The channel profiles have a range of forms consistent with the supposition that they are not static but continually reforming. There are indications that, proximal to the cut, the areas of glial plasma membrane with channel profiles contain more junctional complexes between regenerating cells than between glial cells of normal sheaths. The channel profiles and aggregates of particles belonging to junctions are closely associated when they occupy the same region of the membrane.", "contents": "Trans-glial channels in ventral nerve roots of crayfish. The sheath around the roots of the sixth abdominal ganglion in the ventral nerve cord of the crayfish consists of concentric layers of thin glial processes alternating with wide clefts containing filamentous connective tissue. Regions of each glial lamella are perforated by single, short, tubular channels: the trans-glial channels. In thin plastic sections examined in the electron microscope, the channels appear as slits that are 240 A wide and 450-550 A long which traverse glial lamellae less than 1,500 A thick. Branched tubular channels cross glial sheets that are thicker than 1,500 A. The thickest glial wrap is adaxonal; it closely encapsulates individual axons and its cell membrane is separated from the axolemma by a collagen-free space of only 150 A. The adaxonal glial cytoplasm contains unique, three-dimensional networks of interconnected tubules. Separate tubular lattices occur along these thicker processes. In replicas of freeze-fractured sheaths, the outer half of the plasma membrane belonging to the thin glial sheets exhibits many volcano-like protrusions which represent cross fractures through the necks of trans-glial channels. Corresponding depressions on the inner half of these membranes are sites where the plasma membrane invaginates to form the channels. Although some channels are randomly dispersed, others are lineraly positioned in restricted areas across successive glial layers. The number of channels is far more readily appreciated in replicas than in thin sections. The average frequency of channels is 16 per mu2 (range 8 to 33) in normal roots and does not differ significantly from the average of 13 per mu2 in proximal stumps of roots fixed three to four weeks after the roots were cut. The channels are not precisely aligned from one glial layer to the next but do appear to coincide approximately with the adaxonal tubular lattice. The combination of trans-glial channels and adaxonal tubular lattices may provide a complex conduit that could facilitate a rapid, passive flow of electrolytes and nutrients across the nerve sheath to the axonal surface. Horseradish peroxidase solutions bathing the ventral roots enter the trans-glial channels, extracellular clefts and finally the tubular lattices. This distribution supports the proposed role of the channels in a rapid extracellular passage of solutes. The channel profiles have a range of forms consistent with the supposition that they are not static but continually reforming. There are indications that, proximal to the cut, the areas of glial plasma membrane with channel profiles contain more junctional complexes between regenerating cells than between glial cells of normal sheaths. The channel profiles and aggregates of particles belonging to junctions are closely associated when they occupy the same region of the membrane."} {"id": "PMID:1270621", "title": "Categories of axons in mammalian rami communicantes.", "content": "The present study is an electron microscope analysis of the rami communicantes and its purpose is to determine the functional categories of unmyelinate axons in these nerves. Our findings indicate that the grey rami of segments T7, T8, or T9 in the cat consist of approximately 5,000 unmyelinated axons and 20 myelinated axons, and that these axons are post-ganglionic sympathetics. Although the numbers are new data, this conclusion confirms classic work. The white rami from the same segments contain approximately 3,200 unmyelinated axons and 1,600 myelinated axons. 80-90% of the myelinated axons are preganglionic sympathetics and the remainder are presumably sensory. This conclusion is also in confirmation of classic work. The new conclusions are that approximately 30% of the unmyelinated axons are preganglionic sympathetics, approximately 60% seem to be post-ganglionic sympathetics and the surprisingly small remainder may be sensory.", "contents": "Categories of axons in mammalian rami communicantes. The present study is an electron microscope analysis of the rami communicantes and its purpose is to determine the functional categories of unmyelinate axons in these nerves. Our findings indicate that the grey rami of segments T7, T8, or T9 in the cat consist of approximately 5,000 unmyelinated axons and 20 myelinated axons, and that these axons are post-ganglionic sympathetics. Although the numbers are new data, this conclusion confirms classic work. The white rami from the same segments contain approximately 3,200 unmyelinated axons and 1,600 myelinated axons. 80-90% of the myelinated axons are preganglionic sympathetics and the remainder are presumably sensory. This conclusion is also in confirmation of classic work. The new conclusions are that approximately 30% of the unmyelinated axons are preganglionic sympathetics, approximately 60% seem to be post-ganglionic sympathetics and the surprisingly small remainder may be sensory."} {"id": "PMID:1270622", "title": "A re-examination of anatomical plasticity in the rat retina.", "content": "Previous investigators have reported an increase in numbers of amacrine synapses in the inner plexiform layer (IPL) of the rat retina following light deprivation, and an increase in amacrine along with a decrease in bipolar synapses following light damage. Since there are several points of disagreement between the published reports on this subject we undertook a more detailed study of the effects of light deprivation and light damage on the retina. Four groups of eight male albino rat pups (14 days old) were raised for eight weeks under different conditions: (1) unsutured, bright light reared (UB); (2) bilaterally lid-sutured, bright light reared (SB); (3) unsutured, low light reared (UL); and (4) bilaterally lid-sutured, dark reared (SD). The intensity of the light given the UL group was equated with that striking the corneas of the SB group. Light microscopy showed that the retinas of the SB as well as the UB groups had almost complete degeneration of the outer retinal layers, indicating that even low intensity light, when continuous, causes severe retinal damage. The SD group was thicker in many of the retinal layers compared to the UL (control) group. Electron microscopy revealed that there were no significant changes in the incidences of any type of synapse in the IPL following light deprivation or light damage when averaged over total depth. This is in contradiction to the reports of other investigators. However, when the IPL was analyzed by levels, the incidence of amacrine-ganglion synapses was signficantly greater (p less than 0.05) in groups UB and SD, but only in the outer third of the IPL. Thus, extensive postnatal plasticity of IPL synapses in the rat retina did not occur under our experimental conditions. We found, at best, only limited effects which were confined to the amacrine-ganglion synapses.", "contents": "A re-examination of anatomical plasticity in the rat retina. Previous investigators have reported an increase in numbers of amacrine synapses in the inner plexiform layer (IPL) of the rat retina following light deprivation, and an increase in amacrine along with a decrease in bipolar synapses following light damage. Since there are several points of disagreement between the published reports on this subject we undertook a more detailed study of the effects of light deprivation and light damage on the retina. Four groups of eight male albino rat pups (14 days old) were raised for eight weeks under different conditions: (1) unsutured, bright light reared (UB); (2) bilaterally lid-sutured, bright light reared (SB); (3) unsutured, low light reared (UL); and (4) bilaterally lid-sutured, dark reared (SD). The intensity of the light given the UL group was equated with that striking the corneas of the SB group. Light microscopy showed that the retinas of the SB as well as the UB groups had almost complete degeneration of the outer retinal layers, indicating that even low intensity light, when continuous, causes severe retinal damage. The SD group was thicker in many of the retinal layers compared to the UL (control) group. Electron microscopy revealed that there were no significant changes in the incidences of any type of synapse in the IPL following light deprivation or light damage when averaged over total depth. This is in contradiction to the reports of other investigators. However, when the IPL was analyzed by levels, the incidence of amacrine-ganglion synapses was signficantly greater (p less than 0.05) in groups UB and SD, but only in the outer third of the IPL. Thus, extensive postnatal plasticity of IPL synapses in the rat retina did not occur under our experimental conditions. We found, at best, only limited effects which were confined to the amacrine-ganglion synapses."} {"id": "PMID:1270623", "title": "Anatomical distribution of estrogen target cells in the avian CNS: a comparison with the mammalian CNS.", "content": "The distribution of labeled cells was investigated in the brain of the ring dove one hour after administration of 3H-estradiol. Major areas of concentration of labeled cells were found in (1) the preoptico-strial region: nucleus preopticus medialis and nucleus interstitialis of the dorsal olfactory projection, (2) the basal hypothalamic region: nucleus hypothalamicus posterior medialis and nucleus inferior, (3) the amygdaloid region: nucleus taeniae and adjacent portions of the archistriatum, and (4) the midbrain: substantia grisea surrounding the nucleus mesencephalicus lateralis, pars dorsalis. The findings support the phylogenetic homologies between the avian nucleus interstitialis of the dorsal olfactory projection and the mammalian nucleus interstitialis of the stria terminalis, the avian nucleus hypothalamicus posterior medialis and the mammalian nucleus ventromedialis hypothalami, as well as the avian nucleus inferior and the mammalian nucleus infundibularis-premammillaris ventralis. The results also suggest that the nucleus medialis and other more differentiated labeled areas of the mammalian amygdala.", "contents": "Anatomical distribution of estrogen target cells in the avian CNS: a comparison with the mammalian CNS. The distribution of labeled cells was investigated in the brain of the ring dove one hour after administration of 3H-estradiol. Major areas of concentration of labeled cells were found in (1) the preoptico-strial region: nucleus preopticus medialis and nucleus interstitialis of the dorsal olfactory projection, (2) the basal hypothalamic region: nucleus hypothalamicus posterior medialis and nucleus inferior, (3) the amygdaloid region: nucleus taeniae and adjacent portions of the archistriatum, and (4) the midbrain: substantia grisea surrounding the nucleus mesencephalicus lateralis, pars dorsalis. The findings support the phylogenetic homologies between the avian nucleus interstitialis of the dorsal olfactory projection and the mammalian nucleus interstitialis of the stria terminalis, the avian nucleus hypothalamicus posterior medialis and the mammalian nucleus ventromedialis hypothalami, as well as the avian nucleus inferior and the mammalian nucleus infundibularis-premammillaris ventralis. The results also suggest that the nucleus medialis and other more differentiated labeled areas of the mammalian amygdala."} {"id": "PMID:1270624", "title": "Scanning electron microscopy of the subarachnoid space in the dog. IV. Subarachnoid macrophages.", "content": "Young dogs of both sexes were used in this study. Transmission and scanning electron microscopy were utilized for the examination of the spinal cord and choroid plexus with emphasis on the study of free cells. These procedures were modified so that, in certain cases, the same cells observed in scanning electron microscopy could be analyzed internally by transmission electron microscopy. One half of the animals were injected under anesthesia with horseradish peroxidase for observation of phagocytosis. This study confirms that the free cells observed in the subarachnoid space with the scanning and transmission electron microscopes are identical. The internal morphology of these cells corresponds to that of macrophages. This is further substantiated by the ability of these cells to localize horseradish peroxidase in discrete vacuoles within their cytoplasms. Both pial macrophages and epiplexus cells localize peroxidase in an identical manner in the same animal after one injection. In addition macrophages on the surface of the pia mater respond to extravasated red blood cells in a characteristic manner including phagocytosis. The plentiful population of macrophages on the surface of the pia mater supports the concept that these cells are of major importance in maintaining asepsis in the subarachnoid space.", "contents": "Scanning electron microscopy of the subarachnoid space in the dog. IV. Subarachnoid macrophages. Young dogs of both sexes were used in this study. Transmission and scanning electron microscopy were utilized for the examination of the spinal cord and choroid plexus with emphasis on the study of free cells. These procedures were modified so that, in certain cases, the same cells observed in scanning electron microscopy could be analyzed internally by transmission electron microscopy. One half of the animals were injected under anesthesia with horseradish peroxidase for observation of phagocytosis. This study confirms that the free cells observed in the subarachnoid space with the scanning and transmission electron microscopes are identical. The internal morphology of these cells corresponds to that of macrophages. This is further substantiated by the ability of these cells to localize horseradish peroxidase in discrete vacuoles within their cytoplasms. Both pial macrophages and epiplexus cells localize peroxidase in an identical manner in the same animal after one injection. In addition macrophages on the surface of the pia mater respond to extravasated red blood cells in a characteristic manner including phagocytosis. The plentiful population of macrophages on the surface of the pia mater supports the concept that these cells are of major importance in maintaining asepsis in the subarachnoid space."} {"id": "PMID:1270625", "title": "Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat.", "content": "The present study re-examines, with autoradiographic methods, the pattern of termination of fibers originating from various medio-lateral divisions of the entorhinal cortex on dentate granule cells and on hippocampal pyramidal cells of the rat. Entorhinal fibers were found to distribute in a proximo-distal gradient along the dendrites of dentate granule cells, with afferents from the medial entorhinal area terminating in the innermost portion of the entorhinal synaptic field, afferents from the lateral entorhinal area terminating in the most superficial portions of the entorhinal synaptic field, and intermediate medio-lateral locations in the entorhinal area terminating in intermediate locations in the entorhinal synaptic zone. A similar graded pattern of termination of medial and lateral entorhinal fibers was apparent in the very slight crossed projection of the entorhinal area to the contralateral dentate gyrus. In addition, a comparable gradient in the pattern of termination of entorhinal fibers was evident in the entorhinal projection field in the distal regions of the pyramidal cells of regio inferior of the hippocampus proper. Entorhinal projections to regio superior were, however, organized in quite a different fashion. In this zone, there was no evidence of a proximo-distal gradient in the patterns of termination of medial and lateral entorhinal areas along the dendrites of regio superior pyramidal cells. Rather, the medio-lateral organization was in a longitudinal dimension, with medial entorhinal afferents terminating in the portions of regio superior near the CA1-CA2 transition, and lateral entorhinal afferents terminating furthest from the CA1-CA2 transition, immediately adjacent to the CA1-subicular transition, and in the molecular layer of the subiculum proper. A comparable longitudinal organization of entorhinal projections to regio superior was also evident in the zones of termination of the crossed temporo-ammonic tract, contralateral to the injection. These results demonstrate a heretofore unrecognized complexity in the patterns of projection of the entorhinal area to the hippocampal formation, and illustrate that the entorhinal cortex cannot be divided into only two discrete divisions on the basis of the pattern of projection.", "contents": "Topographic organization of the projections from the entorhinal area to the hippocampal formation of the rat. The present study re-examines, with autoradiographic methods, the pattern of termination of fibers originating from various medio-lateral divisions of the entorhinal cortex on dentate granule cells and on hippocampal pyramidal cells of the rat. Entorhinal fibers were found to distribute in a proximo-distal gradient along the dendrites of dentate granule cells, with afferents from the medial entorhinal area terminating in the innermost portion of the entorhinal synaptic field, afferents from the lateral entorhinal area terminating in the most superficial portions of the entorhinal synaptic field, and intermediate medio-lateral locations in the entorhinal area terminating in intermediate locations in the entorhinal synaptic zone. A similar graded pattern of termination of medial and lateral entorhinal fibers was apparent in the very slight crossed projection of the entorhinal area to the contralateral dentate gyrus. In addition, a comparable gradient in the pattern of termination of entorhinal fibers was evident in the entorhinal projection field in the distal regions of the pyramidal cells of regio inferior of the hippocampus proper. Entorhinal projections to regio superior were, however, organized in quite a different fashion. In this zone, there was no evidence of a proximo-distal gradient in the patterns of termination of medial and lateral entorhinal areas along the dendrites of regio superior pyramidal cells. Rather, the medio-lateral organization was in a longitudinal dimension, with medial entorhinal afferents terminating in the portions of regio superior near the CA1-CA2 transition, and lateral entorhinal afferents terminating furthest from the CA1-CA2 transition, immediately adjacent to the CA1-subicular transition, and in the molecular layer of the subiculum proper. A comparable longitudinal organization of entorhinal projections to regio superior was also evident in the zones of termination of the crossed temporo-ammonic tract, contralateral to the injection. These results demonstrate a heretofore unrecognized complexity in the patterns of projection of the entorhinal area to the hippocampal formation, and illustrate that the entorhinal cortex cannot be divided into only two discrete divisions on the basis of the pattern of projection."} {"id": "PMID:1270626", "title": "The retina and retinal projection on the lamina ganglionaris of the crayfish Pacifastacus leniusculus (Dana).", "content": "The retinular cell morphology and ommatidia arrangement in the crayfish retina are studied. Each ommatidium contains eight receptor cells (R1-R8). Seven of them (R1-R7) contribute to a large spindle-shaped rhabdom with orthogonal layers of microvilli. Distal to the rhabdom of R1-R7, the 8th receptor cell forms a separate rhabdom with horizontal microvilli. The cell is four-lobed, is devoid of screening pigments, and forms a thin axon projecting past the first optic neuropile (lamina ganglionaris) and has a terminal in the second (medulla externa), indicating a separate function of the receptor. The axons from the eight receptors of one ommatidium project to different synaptic compartments (cartridges) in the lamina. A pattern is described where eight axons from three adjacent ommatidia join in one cartridge; and conversely, the axons from one ommatidium split and join to three cartridges. The seven axons from R1-R7 terminate in two levels of the lamina plexiform layer (epl 1 and epl 2), four in the distal and three in the proximal part. Among the monopolar ganglion cells, two types are found with lateral branches restricted to either of the two receptor terminal layers (M3 in epl 1 and M4 in epl 2) and axons terminating in the second optic neuropile. A correlation between the two orthogonal channels for e-vector discrimination and the two levels of terminals within the lamina is suggested. The retina is divided into dorsal and a ventral part with a mirror symmetry axis horizontally in the eye.", "contents": "The retina and retinal projection on the lamina ganglionaris of the crayfish Pacifastacus leniusculus (Dana). The retinular cell morphology and ommatidia arrangement in the crayfish retina are studied. Each ommatidium contains eight receptor cells (R1-R8). Seven of them (R1-R7) contribute to a large spindle-shaped rhabdom with orthogonal layers of microvilli. Distal to the rhabdom of R1-R7, the 8th receptor cell forms a separate rhabdom with horizontal microvilli. The cell is four-lobed, is devoid of screening pigments, and forms a thin axon projecting past the first optic neuropile (lamina ganglionaris) and has a terminal in the second (medulla externa), indicating a separate function of the receptor. The axons from the eight receptors of one ommatidium project to different synaptic compartments (cartridges) in the lamina. A pattern is described where eight axons from three adjacent ommatidia join in one cartridge; and conversely, the axons from one ommatidium split and join to three cartridges. The seven axons from R1-R7 terminate in two levels of the lamina plexiform layer (epl 1 and epl 2), four in the distal and three in the proximal part. Among the monopolar ganglion cells, two types are found with lateral branches restricted to either of the two receptor terminal layers (M3 in epl 1 and M4 in epl 2) and axons terminating in the second optic neuropile. A correlation between the two orthogonal channels for e-vector discrimination and the two levels of terminals within the lamina is suggested. The retina is divided into dorsal and a ventral part with a mirror symmetry axis horizontally in the eye."} {"id": "PMID:1270627", "title": "Synaptogenesis in the ventromedial hypothalamus of the prenatal mouse.", "content": "Mouse embryos from day 13 to day 19 of gestation (E13 through E19) were removed by Caesarean section and their brains were prepared for electron microscopy. Coronal sections were examined in three planes through the ventromedial hypothalamus: anterior, the level at which the optic tracts pass posterolaterally to become partially enclosed in the major brain mass; middle, the level at which the floor of the third ventricle begins to widen and flatten; posterior, the level at which the most anterior infundibulum appears. Three types of junctional complexes were examined. Close junctions are identified as straight, parallel areas of two apposed membranes which appear more electron-dense than immediately adjacent regions. The membranes are separated by a clearly visible cleft. Unlike synapses, no clear synaptic vesicles are found in either of the adjacent profiles unless randomly distributed and accompanied by ribosomes or glycogen. Close junctions are seen most frequently on day E15, then decrease in number through E19. Their participation in synaptogenesis is discussed from temporal, morphological, distributional and quantitative perspectives and is provisionally rejected. Immature synapses show only the minimal membrane specialization found in close junctions, but vesicles are present, ribosomes absent in at least one of the adjacent cytoplasms. Their appearance peaks on E17-E18, paralleling and slightly preceding that of the mature synapses. Their evolution from close junctions has only weak temporal support. Mature synapses display the cytoplasmic densities which immature synapses lack. They attain their greatest prenatal numbers on E18, then decrease in number on E19. The conclusion is advanced that synaptogenesis does--or at least can--occur without the prior appearance of avesicular regions of increased membrane density.", "contents": "Synaptogenesis in the ventromedial hypothalamus of the prenatal mouse. Mouse embryos from day 13 to day 19 of gestation (E13 through E19) were removed by Caesarean section and their brains were prepared for electron microscopy. Coronal sections were examined in three planes through the ventromedial hypothalamus: anterior, the level at which the optic tracts pass posterolaterally to become partially enclosed in the major brain mass; middle, the level at which the floor of the third ventricle begins to widen and flatten; posterior, the level at which the most anterior infundibulum appears. Three types of junctional complexes were examined. Close junctions are identified as straight, parallel areas of two apposed membranes which appear more electron-dense than immediately adjacent regions. The membranes are separated by a clearly visible cleft. Unlike synapses, no clear synaptic vesicles are found in either of the adjacent profiles unless randomly distributed and accompanied by ribosomes or glycogen. Close junctions are seen most frequently on day E15, then decrease in number through E19. Their participation in synaptogenesis is discussed from temporal, morphological, distributional and quantitative perspectives and is provisionally rejected. Immature synapses show only the minimal membrane specialization found in close junctions, but vesicles are present, ribosomes absent in at least one of the adjacent cytoplasms. Their appearance peaks on E17-E18, paralleling and slightly preceding that of the mature synapses. Their evolution from close junctions has only weak temporal support. Mature synapses display the cytoplasmic densities which immature synapses lack. They attain their greatest prenatal numbers on E18, then decrease in number on E19. The conclusion is advanced that synaptogenesis does--or at least can--occur without the prior appearance of avesicular regions of increased membrane density."} {"id": "PMID:1270628", "title": "Descending pathways from the brain stem to the spinal cord in some reptiles. I. Origin.", "content": "In the present study of the origin of the pathways descending from the brain stem to the spinal cord has been investigated in the reptiles Testudo hermanni, Pseudemys scripta elegans, Tupinambis nigropunctatus and Python reticulatus. These reptiles, using highly different types of progression, have been selected, because fundamental variations in the organization of the central motor apparatus are to be expected. The origin of the descending pathways has been demonstrated by recording the occurrence of retrograde cell changes following hemicordotomies and by searching for labeled cells following injection into the spinal cord of the enzyme horseradish peroxidase. In the reptiles studies the presence of interstitiospinal, vestibulospinal and reticulospinal pathways could be demonstrated. A crossed rubrospinal tract has been shown in the turtles and in the lizard, but could not be demonstrated in the Python. The presence of a direct tectospinal pathway could not be shown.", "contents": "Descending pathways from the brain stem to the spinal cord in some reptiles. I. Origin. In the present study of the origin of the pathways descending from the brain stem to the spinal cord has been investigated in the reptiles Testudo hermanni, Pseudemys scripta elegans, Tupinambis nigropunctatus and Python reticulatus. These reptiles, using highly different types of progression, have been selected, because fundamental variations in the organization of the central motor apparatus are to be expected. The origin of the descending pathways has been demonstrated by recording the occurrence of retrograde cell changes following hemicordotomies and by searching for labeled cells following injection into the spinal cord of the enzyme horseradish peroxidase. In the reptiles studies the presence of interstitiospinal, vestibulospinal and reticulospinal pathways could be demonstrated. A crossed rubrospinal tract has been shown in the turtles and in the lizard, but could not be demonstrated in the Python. The presence of a direct tectospinal pathway could not be shown."} {"id": "PMID:1270629", "title": "Descending pathways from the brain stem to the spinal cord in some reptiles. II. Course and site of termination.", "content": "The course and termination of the pathways descending from the brain stem to the spinal cord have been studied by tracing the ensuing anterograde fiber degeneration, following appropriate lesions in the reptiles Testudo hermanni, Tupinambis nigropunctatus and Python reticulatus. In these reptiles the presence of interstitiospinal, vestibulospinal and reticulospinal pathways has been demonstrated. A crossed rubrospinal tract has been shown in the turtle and lizard, but could not be demonstrated in the Python. The presence of a tectospinal pathway of any importance could not be shown. However, the tectum mesencephali has been found to project profusely to the brain stem reticular formation. The interstitiospinal tract projects predominantly to the ipsilateral side of the spinal cord. The vestibulospinal projection, arising from the large-celled nucleus vestibularis ventrolateralis, comprises a large uncrossed and a small decussating component. The rubrospinal pathway terminates in a particular area of the spinal gray, i.e., the intermediate zone, whereas the interstitiospainal, reticulospinal and vestibulospinal tracts all terminate in the medial part of the ventral horn. It appeared that the classification of descending pathways as advocated in mammals by Kuypers ('64) into lateral and medial systems can be readily applied to reptiles. The lateral system terminates in the dorsal and lateral parts of the intermediate zone, the medial system predominantely in the dorsomedial part of the ventral horn. This classification renders it likely that the absence of a lateral focus of termination as well as the absence of a rubrospinal tract in the Python, is correlated to the absence of limbs. A comparison of experimental data concerning the systems descending from the brain stem to the spinal cord in amphibians, reptiles, birds and mammals suggests that these systems with regard to origin, course and termination have a basic pattern in common.", "contents": "Descending pathways from the brain stem to the spinal cord in some reptiles. II. Course and site of termination. The course and termination of the pathways descending from the brain stem to the spinal cord have been studied by tracing the ensuing anterograde fiber degeneration, following appropriate lesions in the reptiles Testudo hermanni, Tupinambis nigropunctatus and Python reticulatus. In these reptiles the presence of interstitiospinal, vestibulospinal and reticulospinal pathways has been demonstrated. A crossed rubrospinal tract has been shown in the turtle and lizard, but could not be demonstrated in the Python. The presence of a tectospinal pathway of any importance could not be shown. However, the tectum mesencephali has been found to project profusely to the brain stem reticular formation. The interstitiospinal tract projects predominantly to the ipsilateral side of the spinal cord. The vestibulospinal projection, arising from the large-celled nucleus vestibularis ventrolateralis, comprises a large uncrossed and a small decussating component. The rubrospinal pathway terminates in a particular area of the spinal gray, i.e., the intermediate zone, whereas the interstitiospainal, reticulospinal and vestibulospinal tracts all terminate in the medial part of the ventral horn. It appeared that the classification of descending pathways as advocated in mammals by Kuypers ('64) into lateral and medial systems can be readily applied to reptiles. The lateral system terminates in the dorsal and lateral parts of the intermediate zone, the medial system predominantely in the dorsomedial part of the ventral horn. This classification renders it likely that the absence of a lateral focus of termination as well as the absence of a rubrospinal tract in the Python, is correlated to the absence of limbs. A comparison of experimental data concerning the systems descending from the brain stem to the spinal cord in amphibians, reptiles, birds and mammals suggests that these systems with regard to origin, course and termination have a basic pattern in common."} {"id": "PMID:1270630", "title": "Involvement of the avian hypothalamus in defensively conditioned heart rate change.", "content": "Hypothalamic involvement in visually conditioned heart rate change (established by pairing light and foot-shock) was studied in 128 pigeons by evaluating conditioning performance following lesions of various hypothalamic areas. Extensive destruction of the posterior hypothalamus severely impaired development of conditioned heart rate change. Anterior hypothalamic lesions also produced serious deficits, though not as severe as following posterior hypothalamic damage. Partial posterior hypothalamic, unilateral and tuberal lesions produced only minor to moderate deficits. The critical locus for profound impairment of conditioned response development appeared to be the medial hypothalamus, and it is suggested that more specifically it is the terminal field of the archistriatal projection upon the medial hypothalamus. It is concluded that the medial hypothalamus is essential for the development of defensively conditioned heart rate change, and based on previous findings it is suggested that the critical descending pathway for expression of this conditioned response involves the archistriatal projection upon the medial hypothalamus and subsequently a polysynaptic pathway through the ventral brainstem.", "contents": "Involvement of the avian hypothalamus in defensively conditioned heart rate change. Hypothalamic involvement in visually conditioned heart rate change (established by pairing light and foot-shock) was studied in 128 pigeons by evaluating conditioning performance following lesions of various hypothalamic areas. Extensive destruction of the posterior hypothalamus severely impaired development of conditioned heart rate change. Anterior hypothalamic lesions also produced serious deficits, though not as severe as following posterior hypothalamic damage. Partial posterior hypothalamic, unilateral and tuberal lesions produced only minor to moderate deficits. The critical locus for profound impairment of conditioned response development appeared to be the medial hypothalamus, and it is suggested that more specifically it is the terminal field of the archistriatal projection upon the medial hypothalamus. It is concluded that the medial hypothalamus is essential for the development of defensively conditioned heart rate change, and based on previous findings it is suggested that the critical descending pathway for expression of this conditioned response involves the archistriatal projection upon the medial hypothalamus and subsequently a polysynaptic pathway through the ventral brainstem."} {"id": "PMID:1270631", "title": "Glial changes in the progress of a chemical lesion. An electron microscopic study.", "content": "The response of non-neuronal cells in the brain to monosodium glutamate (MSG) was studied in the neonatal mouse brain. Neurons rapidly degenerate in this chemically-induced lesion, and the glia reflect and respond to their early pyknosis and death. Astrocytic glia exhibit the most profound responses in the form of degenerative nuclear and cytoplasmic changes within 15 to 20 minutes after ingestion of MSG. After 6 to 12 hours, a large glial cell population, containing neuronal and synaptic debris, can be seen. Recovery of severely damaged astrocytes is unlikely. Further, evidence of multiplication of uninjured cells to supply this observed repopulation was found. Microglia start to engulf debris at 6 to 12 hours and continue this process through at least 48 hours. From 3 to 48 hours, a third cell type, tentatively identified as a Gitter cell, is preminently involved in phagocytosis of neuronal elements. Nuclei of these cells enlarge and their parikarya become vastly expanded in a fashion typical of Gitter cells. These cells appear to represent the transformed microglia. Phagocytosis following a chemical lesion induced by glutamic acid, a neurotransmitter substance, is exceedingly rapid in comparison to that elicited by other types of lesions. Further, endogenous glial cells cope with the cellular debris; no participation in this process by hematogenous cells was observed.", "contents": "Glial changes in the progress of a chemical lesion. An electron microscopic study. The response of non-neuronal cells in the brain to monosodium glutamate (MSG) was studied in the neonatal mouse brain. Neurons rapidly degenerate in this chemically-induced lesion, and the glia reflect and respond to their early pyknosis and death. Astrocytic glia exhibit the most profound responses in the form of degenerative nuclear and cytoplasmic changes within 15 to 20 minutes after ingestion of MSG. After 6 to 12 hours, a large glial cell population, containing neuronal and synaptic debris, can be seen. Recovery of severely damaged astrocytes is unlikely. Further, evidence of multiplication of uninjured cells to supply this observed repopulation was found. Microglia start to engulf debris at 6 to 12 hours and continue this process through at least 48 hours. From 3 to 48 hours, a third cell type, tentatively identified as a Gitter cell, is preminently involved in phagocytosis of neuronal elements. Nuclei of these cells enlarge and their parikarya become vastly expanded in a fashion typical of Gitter cells. These cells appear to represent the transformed microglia. Phagocytosis following a chemical lesion induced by glutamic acid, a neurotransmitter substance, is exceedingly rapid in comparison to that elicited by other types of lesions. Further, endogenous glial cells cope with the cellular debris; no participation in this process by hematogenous cells was observed."} {"id": "PMID:1270632", "title": "Organization of the tectofugal visual pathway in the pigeon: a retrograde transport study.", "content": "In birds, superficial laminae of the optic tectum receive a massive retinal input; the tectum in turn projects upon the nucleus rotundus thalami, which then sends its efferents to the ectostriatal core of the telencephalon. To examine the detailed organization of this principal ascending visual pathway, small injections of the marker horseradish peroxidase (HRP) were placed in various sites throughout the ectostriatum (E) or nucleus rotundus (Rt) in pigeons. Analysis of the resulting patterns of retrograde labeling indicates the tectofugal pathway to be comprised of at least five different channels. Cells which lie at various depths in the stratum griseum centrale (SGC) of the tectum project upon distinct subdivisions of nucleus rotundus. Anterior portions of Rt receive input from superficial-most cells in the SGC, while medial and more caudal portions of Rt are projected upon by deeper SGC neurons. A ventral subdivision of Rt was found to receive its primary input from two pretectal nuclei. Additional inputs to all portions of Rt arise from nucleus reticularis superior thalami. The various subdivisions of rotundus in turn project upon distinct portions of the ectostriatum. Thus, the segregation between the different input classes into Rt is largely retained at the telencephalic level. In contrast, the nucleus triangularis, a dorso-medial extension of Rt which receives its input from the deepest of all SGC neurons, sends its efferents to all parts of the ectostriatum.", "contents": "Organization of the tectofugal visual pathway in the pigeon: a retrograde transport study. In birds, superficial laminae of the optic tectum receive a massive retinal input; the tectum in turn projects upon the nucleus rotundus thalami, which then sends its efferents to the ectostriatal core of the telencephalon. To examine the detailed organization of this principal ascending visual pathway, small injections of the marker horseradish peroxidase (HRP) were placed in various sites throughout the ectostriatum (E) or nucleus rotundus (Rt) in pigeons. Analysis of the resulting patterns of retrograde labeling indicates the tectofugal pathway to be comprised of at least five different channels. Cells which lie at various depths in the stratum griseum centrale (SGC) of the tectum project upon distinct subdivisions of nucleus rotundus. Anterior portions of Rt receive input from superficial-most cells in the SGC, while medial and more caudal portions of Rt are projected upon by deeper SGC neurons. A ventral subdivision of Rt was found to receive its primary input from two pretectal nuclei. Additional inputs to all portions of Rt arise from nucleus reticularis superior thalami. The various subdivisions of rotundus in turn project upon distinct portions of the ectostriatum. Thus, the segregation between the different input classes into Rt is largely retained at the telencephalic level. In contrast, the nucleus triangularis, a dorso-medial extension of Rt which receives its input from the deepest of all SGC neurons, sends its efferents to all parts of the ectostriatum."} {"id": "PMID:1270642", "title": "Uses of double-pulse stimulation behaviorally to infer refractoriness, summation, convergence, and transmitter characteristics of hypothalamic reward systems.", "content": "To self-administer trains of pulse pairs, rats with electrodes in the hypothalamic reward system would press a lever at lower current thresholds or faster latencies, the shorter the intrapair interval--unless the interval was so short that each second pulse fell within the refractory period following the first. By delivering all second pulses to the contralateral reward system not only was this refractory period limitation on temporal summation circumvented but spatial summation of the two reward systems was demonstrated. Evidently, they converge somewhere upon common neurons. Nearby nonreward structures did not share in this convergence. Assuming that the temporal-summation decline at longer intrapair intervals reflected the course of transmitter disposal at the synapse, imipramine and diisopropylfluorophosphate were peripherally administered. These drugs, which retard disposal, respectively, in adrenergic and cholinergic synapses, indeed prolonged temporal summation, thus, supporting the assumption and implying that adrenergic and cholinergic mechanisms both mediate self-stimulation.", "contents": "Uses of double-pulse stimulation behaviorally to infer refractoriness, summation, convergence, and transmitter characteristics of hypothalamic reward systems. To self-administer trains of pulse pairs, rats with electrodes in the hypothalamic reward system would press a lever at lower current thresholds or faster latencies, the shorter the intrapair interval--unless the interval was so short that each second pulse fell within the refractory period following the first. By delivering all second pulses to the contralateral reward system not only was this refractory period limitation on temporal summation circumvented but spatial summation of the two reward systems was demonstrated. Evidently, they converge somewhere upon common neurons. Nearby nonreward structures did not share in this convergence. Assuming that the temporal-summation decline at longer intrapair intervals reflected the course of transmitter disposal at the synapse, imipramine and diisopropylfluorophosphate were peripherally administered. These drugs, which retard disposal, respectively, in adrenergic and cholinergic synapses, indeed prolonged temporal summation, thus, supporting the assumption and implying that adrenergic and cholinergic mechanisms both mediate self-stimulation."} {"id": "PMID:1270643", "title": "Time-discrimination performance in cats with lesions in prefrontal cortex and caudate nucleus.", "content": "Cats were trained on a time-discrimination task in which different periods of bodily confinement served as discriminanda for go-left/go-right responding. Lesions of gyrus proreus or the associated anteroventral part of nucleus caudatus impaired relearning in this situation. After reacquisition, animals with caudate lesions received proreal ablations and animals with cortical damage received caudate lesions; both additional lesions caused reappearance of the deficit. The absence of external stimuli to signal locus of reinforcement at the moment of spatial choice may have been crucial for eliciting the deficit. The data support the notion that the prefrontal cortex and the anatomically related part of the caudate nucleus participate in similar behaviors.", "contents": "Time-discrimination performance in cats with lesions in prefrontal cortex and caudate nucleus. Cats were trained on a time-discrimination task in which different periods of bodily confinement served as discriminanda for go-left/go-right responding. Lesions of gyrus proreus or the associated anteroventral part of nucleus caudatus impaired relearning in this situation. After reacquisition, animals with caudate lesions received proreal ablations and animals with cortical damage received caudate lesions; both additional lesions caused reappearance of the deficit. The absence of external stimuli to signal locus of reinforcement at the moment of spatial choice may have been crucial for eliciting the deficit. The data support the notion that the prefrontal cortex and the anatomically related part of the caudate nucleus participate in similar behaviors."} {"id": "PMID:1270644", "title": "The dorsal tegmental noradrenergic projection: an analysis of its role in maze learning.", "content": "The hypothesis that the noradrenergic projection from the locus coeruleus (LC) to the cerebral cortex and hippocampus is an important neural substrate for learning was evaluated. Maze performance was studied in rats receiving either electrolytic lesions of LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal tegmental noradrenergic projection. The LC lesions did not disrupt the acquisition of a running response for food reinforcement in an L-shaped runway, even though hippocampal-cortical norepinephrine (NE) was reduced to 29%. Greater telencephalic NE depletions (to 6% of control levels) produced by 6-OHDA also failed to disrupt the acquisition of this behavior or to impair the acquisition of a food-reinforced position habit in a T-maze. Neither locomotor activity nor habituation to a novel environment was affected by the 6-OHDA lesions. Rats with such lesions were, however, found to be significantly more distractible than were controls during the performance of a previously trained response. The hypothesis that telencephalic NE is of fundamental importance in learning was not supported. The data suggest that this system may participate in attentional mechanisms.", "contents": "The dorsal tegmental noradrenergic projection: an analysis of its role in maze learning. The hypothesis that the noradrenergic projection from the locus coeruleus (LC) to the cerebral cortex and hippocampus is an important neural substrate for learning was evaluated. Maze performance was studied in rats receiving either electrolytic lesions of LC or 6-hydroxydopamine (6-OHDA) lesions of the dorsal tegmental noradrenergic projection. The LC lesions did not disrupt the acquisition of a running response for food reinforcement in an L-shaped runway, even though hippocampal-cortical norepinephrine (NE) was reduced to 29%. Greater telencephalic NE depletions (to 6% of control levels) produced by 6-OHDA also failed to disrupt the acquisition of this behavior or to impair the acquisition of a food-reinforced position habit in a T-maze. Neither locomotor activity nor habituation to a novel environment was affected by the 6-OHDA lesions. Rats with such lesions were, however, found to be significantly more distractible than were controls during the performance of a previously trained response. The hypothesis that telencephalic NE is of fundamental importance in learning was not supported. The data suggest that this system may participate in attentional mechanisms."} {"id": "PMID:1270645", "title": "Roles of anoxia and noise-induced hearing loss in the postictal refractory period for audiogenic seizures in mice.", "content": "The present series of experiments demonstrated a postictal refractory period for audiogenic seizures in DBA/2J mice, which was not related to hearing loss but apparently was related to anoxia. Unlike many previous studies, Experiment 1 controlled for the effects of noise exposure upon hearing sensitivity and demonstrated reduced susceptibility to subsequent audiogenic seizures for at least 1 hr after initial clonic-tonic convulsions. The postictal refractory period was shown to result from the occurrence of seizures per se, not from noise exposure alone. Experiment 2 demonstrated deficiencies of sensorimotor functions that accompanied reduced postictal seizure susceptibility. The two phenomena had similar time courses of recovery, which suggested a common mechanism, probably anoxia, associated with the initial convulsions. In support of this view, Experiment 3 showed that recovery from both phenomena was expedited by allowing subjects to breathe increased O2. The role of anoxia in fatal convulsions was suggested by the finding that subjects experiencing clonic-tonic convulsions in a high-O2 environment survived without exception. In contrast, seizures of air-breathing controls were almost always fatal. Taken together, the data indicate that the postictal reduced susceptibility to audiogenic seizures was closely related to metabolic depletion (in particular, anoxia). The pattern of recovery of susceptibility further suggests that the effects of anoxia impair the spread of seizure activity through the central nervous system, although the initiation of seizures is also affected for a short time.", "contents": "Roles of anoxia and noise-induced hearing loss in the postictal refractory period for audiogenic seizures in mice. The present series of experiments demonstrated a postictal refractory period for audiogenic seizures in DBA/2J mice, which was not related to hearing loss but apparently was related to anoxia. Unlike many previous studies, Experiment 1 controlled for the effects of noise exposure upon hearing sensitivity and demonstrated reduced susceptibility to subsequent audiogenic seizures for at least 1 hr after initial clonic-tonic convulsions. The postictal refractory period was shown to result from the occurrence of seizures per se, not from noise exposure alone. Experiment 2 demonstrated deficiencies of sensorimotor functions that accompanied reduced postictal seizure susceptibility. The two phenomena had similar time courses of recovery, which suggested a common mechanism, probably anoxia, associated with the initial convulsions. In support of this view, Experiment 3 showed that recovery from both phenomena was expedited by allowing subjects to breathe increased O2. The role of anoxia in fatal convulsions was suggested by the finding that subjects experiencing clonic-tonic convulsions in a high-O2 environment survived without exception. In contrast, seizures of air-breathing controls were almost always fatal. Taken together, the data indicate that the postictal reduced susceptibility to audiogenic seizures was closely related to metabolic depletion (in particular, anoxia). The pattern of recovery of susceptibility further suggests that the effects of anoxia impair the spread of seizure activity through the central nervous system, although the initiation of seizures is also affected for a short time."} {"id": "PMID:1270646", "title": "Circadian rhythms and partial recovery of regulatory drinking in rats after lateral hypothalamic lesions.", "content": "Rats that had recovered spontaneous ingestive behavior after lesions of the lateral hypothalamus were challenged with acute injections of hypertonic NaCl administered at different times during the day/night cycle. Following these injections, drinking was observed only during the nighttime. After morning injections the rats frequently waited until nightfall before drinking, whereas animals injected at night showed much shorter delays in the behavioral response; a similar nocturnal predominance of drinking was seen after food deprivation and in the ad-lib situation. Studies in blinded animals suggested that these effects were due to an endogenous circadian rhythm.", "contents": "Circadian rhythms and partial recovery of regulatory drinking in rats after lateral hypothalamic lesions. Rats that had recovered spontaneous ingestive behavior after lesions of the lateral hypothalamus were challenged with acute injections of hypertonic NaCl administered at different times during the day/night cycle. Following these injections, drinking was observed only during the nighttime. After morning injections the rats frequently waited until nightfall before drinking, whereas animals injected at night showed much shorter delays in the behavioral response; a similar nocturnal predominance of drinking was seen after food deprivation and in the ad-lib situation. Studies in blinded animals suggested that these effects were due to an endogenous circadian rhythm."} {"id": "PMID:1270647", "title": "Sensitivity to low doses of ethanol and pentobarbital in mice selected for sensitivity to hypnotic doses of ethanol.", "content": "These experiments assessed sensitivity to low doses of ethanol and pentobarbital in mice that had been selectively bred with respect to ethanol sleep time (the length of time an animal remains on its back following a hypnotic dose of ethanol). The hypothesis under investigation was that short-sleep (SS) mice might be more sensitive than long-sleep (LS) mice to excitatory effects produced by low doses of depressants. In support of this hypothesis SS mice were more active in an open-field test after ethanol than were LS mice. The lines did not differ in performance on a rotating-rod apparatus after these same doses of ethanol, suggesting that the difference in open-field activity was not attributable to a greater impairment of locomotor activity in LS mice. A similar difference in the open-field activity of the selected lines was observed with pentobarbital.", "contents": "Sensitivity to low doses of ethanol and pentobarbital in mice selected for sensitivity to hypnotic doses of ethanol. These experiments assessed sensitivity to low doses of ethanol and pentobarbital in mice that had been selectively bred with respect to ethanol sleep time (the length of time an animal remains on its back following a hypnotic dose of ethanol). The hypothesis under investigation was that short-sleep (SS) mice might be more sensitive than long-sleep (LS) mice to excitatory effects produced by low doses of depressants. In support of this hypothesis SS mice were more active in an open-field test after ethanol than were LS mice. The lines did not differ in performance on a rotating-rod apparatus after these same doses of ethanol, suggesting that the difference in open-field activity was not attributable to a greater impairment of locomotor activity in LS mice. A similar difference in the open-field activity of the selected lines was observed with pentobarbital."} {"id": "PMID:1270648", "title": "Relationship between composition and stability of bovine milk lysozyme.", "content": "The amino acid analysis, peptide mapping, and heat stability of bovine milk lysozyme are presented. The bovine milk lysozyme molecule contains approximately 154 amino acids and is strikingly different in amino acid content from human milk lysozyme and egg white lysozyme. Tryptic hydrolysis yielded 26 peptides, all of which are unique from tryptic peptides of human milk lysozyme and egg white lysozyme. In addition, bovine milk lysozyme was more heat stable than human milk lysozyme at pH 4.0 but more labile at pH 7.0 and 9.0. Possible explanations for the differences in heat stability are discussed.", "contents": "Relationship between composition and stability of bovine milk lysozyme. The amino acid analysis, peptide mapping, and heat stability of bovine milk lysozyme are presented. The bovine milk lysozyme molecule contains approximately 154 amino acids and is strikingly different in amino acid content from human milk lysozyme and egg white lysozyme. Tryptic hydrolysis yielded 26 peptides, all of which are unique from tryptic peptides of human milk lysozyme and egg white lysozyme. In addition, bovine milk lysozyme was more heat stable than human milk lysozyme at pH 4.0 but more labile at pH 7.0 and 9.0. Possible explanations for the differences in heat stability are discussed."} {"id": "PMID:1270649", "title": "Limiting amino acid for protein synthesis with mammary cells in tissue culture.", "content": "To identify the limiting amino acid in the minimal essential medium as published by Eagle (Science 130:432, 1959) for milk protein synthesis in rat mammary cells in tissue culture, two different experimental approaches were used. The first study involved the reduction of amino acids singly from the total amino acid complement of the medium for milk protein synthesis. The second study was to investigate the effect on milk protein synthesis of single amino acid addition to the basic complement of amino acids. Order of limiting amino acids was lysine (first) and possible methionine, valine, or arginine (second).", "contents": "Limiting amino acid for protein synthesis with mammary cells in tissue culture. To identify the limiting amino acid in the minimal essential medium as published by Eagle (Science 130:432, 1959) for milk protein synthesis in rat mammary cells in tissue culture, two different experimental approaches were used. The first study involved the reduction of amino acids singly from the total amino acid complement of the medium for milk protein synthesis. The second study was to investigate the effect on milk protein synthesis of single amino acid addition to the basic complement of amino acids. Order of limiting amino acids was lysine (first) and possible methionine, valine, or arginine (second)."} {"id": "PMID:1270650", "title": "Effect of a synthetic corticoid on milk yield and composition and on blood metabolites and hormones in dairy cows.", "content": "Twenty-five dairy cows were assigned randomly by breed to flumethasone treatment (10 mug/day, 13 cows) or placebo control (12 cows) from 4 to 44 wk of lactation. Lactation means and trends with stage of lactation were treatment responses. Mean milk yields of cows supplemented with flumethasone were not significantly different from controls. Mean metabolite (glucose, nonesterified fatty acids, and total esterified fatty acids) and hormone concentrations (corticoids, insulin, and prolactin) of blood plasma and their trends throughout lactation were unaffected by supplementation. Data were pooled to determine effects of stage of lactation, temperature, pregnancy, and month on these variables. Changes during lactation were systematic for feed intake, body weight, milk yield, milk components except somatic cells, blood metabolites, and prolactin. At environmental temperatures above 18 C, effects were consistently negative for milk yield and composition, but only above 26 C for feed intake. Prolactin of plasma increased with increasing temperature to 18.2 C and then decreased. No other plasma metabolite or hormone was affected by days pregnant, age, or temperature. Months affected feed intake, milk yield, milk fat percentages, all blood metabolites, and prolactin. Prolactin concentrations increased as daylight hours increased. Our inability to augment established lactation by feeding a supplement of synthetic glucocorticoid to lactating cows is consistent with the view that a lack of avialable corticoids does not limit persistency of lactation in the cow.", "contents": "Effect of a synthetic corticoid on milk yield and composition and on blood metabolites and hormones in dairy cows. Twenty-five dairy cows were assigned randomly by breed to flumethasone treatment (10 mug/day, 13 cows) or placebo control (12 cows) from 4 to 44 wk of lactation. Lactation means and trends with stage of lactation were treatment responses. Mean milk yields of cows supplemented with flumethasone were not significantly different from controls. Mean metabolite (glucose, nonesterified fatty acids, and total esterified fatty acids) and hormone concentrations (corticoids, insulin, and prolactin) of blood plasma and their trends throughout lactation were unaffected by supplementation. Data were pooled to determine effects of stage of lactation, temperature, pregnancy, and month on these variables. Changes during lactation were systematic for feed intake, body weight, milk yield, milk components except somatic cells, blood metabolites, and prolactin. At environmental temperatures above 18 C, effects were consistently negative for milk yield and composition, but only above 26 C for feed intake. Prolactin of plasma increased with increasing temperature to 18.2 C and then decreased. No other plasma metabolite or hormone was affected by days pregnant, age, or temperature. Months affected feed intake, milk yield, milk fat percentages, all blood metabolites, and prolactin. Prolactin concentrations increased as daylight hours increased. Our inability to augment established lactation by feeding a supplement of synthetic glucocorticoid to lactating cows is consistent with the view that a lack of avialable corticoids does not limit persistency of lactation in the cow."} {"id": "PMID:1270651", "title": "Failure to demonstrate transfer of milk prolactin into blood of milk-fed rats and calves.", "content": "Possible absorption of ingested prolactin into blood of milk-fed neonates was studied in two species by different experimental approaches. In calves, secretion of endogenous prolactin was suppressed by administration of ergocryptine. Prolactin was measured in blood plasma at 20-min intervals before and after ingestion by the calves of bovine milk or colostrum which contained prolactin. Prolactin in plasma during the 2-h period after feeding was the same as that during the 1-h period before feeding. therefore, these data failed to demonstrate any absorption of ingested prolactin into the blood of neonatal calves. Previous research showed that bovine prolactin could be transferred into rat milk by injecting it into lactating rats. Blood serum was collected from rat pups that were suckling dams previously injected with bovine prolactin. Several dosages and times of administration were used in the experimental design, and blood serum also was collected from rat pups nursing control dams. All samples were immunoassayed for bovine prolactin with reagents that crossreacted only slightly with endogenous rat prolactin. Injection of lactating dams with bovine prolactin did not increase the amount of immunoreactive bovine prolactin in the sera of suckling rat pups. These results agree with those from the calf study and indicate that ingested bovine prolactin was not absorbed intact into the blood of neonatal rats.", "contents": "Failure to demonstrate transfer of milk prolactin into blood of milk-fed rats and calves. Possible absorption of ingested prolactin into blood of milk-fed neonates was studied in two species by different experimental approaches. In calves, secretion of endogenous prolactin was suppressed by administration of ergocryptine. Prolactin was measured in blood plasma at 20-min intervals before and after ingestion by the calves of bovine milk or colostrum which contained prolactin. Prolactin in plasma during the 2-h period after feeding was the same as that during the 1-h period before feeding. therefore, these data failed to demonstrate any absorption of ingested prolactin into the blood of neonatal calves. Previous research showed that bovine prolactin could be transferred into rat milk by injecting it into lactating rats. Blood serum was collected from rat pups that were suckling dams previously injected with bovine prolactin. Several dosages and times of administration were used in the experimental design, and blood serum also was collected from rat pups nursing control dams. All samples were immunoassayed for bovine prolactin with reagents that crossreacted only slightly with endogenous rat prolactin. Injection of lactating dams with bovine prolactin did not increase the amount of immunoreactive bovine prolactin in the sera of suckling rat pups. These results agree with those from the calf study and indicate that ingested bovine prolactin was not absorbed intact into the blood of neonatal rats."} {"id": "PMID:1270652", "title": "Rumen volatile fatty acids and milk composition from cows fed hay, haylage, or urea-treated corn silage.", "content": "Alfalfa-brome hay, haylage, .5% urea-treated corn silage, or .5% urea plus 1% dried whey-treated corn silage was fed as the only forage to one of four groups of 10 lactating cows per group for a lactation trial of 10 wk. Rumen samples were collected via stomach tube 3 to 4 h after the morning feeding. The pH of the rumen samples from cows fed hay was higher than for cows fed haylage, urea-treated corn silage, and urea-whey corn silage, 6.69 versus 6.36, 6.40, and 6.50. Total volatile fatty acids and propionate were highest from cows fed urea-whey corn silage and were higher on all three fermented forages than cows fed hay. Acetate/propionate ratio was highest from cows fed hay and lowest from cows fed corn silages. Butyrate was highest from cows fed haylage or hay. Milk protein composition was not affected by ration although nonprotein nitrogen of milk was highest from cows fed the urea-treated corn silages. Oleic acid and total unsaturated fatty acids were lowest in milk fat from cows fed hay while palmitic acid was highest from cows fed hay and haylage. These results suggest that type of forage fed may cause small changes in rumen fermentation and in milk composition. The importance of these changes is unknown but may affect properties of dairy products produced from this milk.", "contents": "Rumen volatile fatty acids and milk composition from cows fed hay, haylage, or urea-treated corn silage. Alfalfa-brome hay, haylage, .5% urea-treated corn silage, or .5% urea plus 1% dried whey-treated corn silage was fed as the only forage to one of four groups of 10 lactating cows per group for a lactation trial of 10 wk. Rumen samples were collected via stomach tube 3 to 4 h after the morning feeding. The pH of the rumen samples from cows fed hay was higher than for cows fed haylage, urea-treated corn silage, and urea-whey corn silage, 6.69 versus 6.36, 6.40, and 6.50. Total volatile fatty acids and propionate were highest from cows fed urea-whey corn silage and were higher on all three fermented forages than cows fed hay. Acetate/propionate ratio was highest from cows fed hay and lowest from cows fed corn silages. Butyrate was highest from cows fed haylage or hay. Milk protein composition was not affected by ration although nonprotein nitrogen of milk was highest from cows fed the urea-treated corn silages. Oleic acid and total unsaturated fatty acids were lowest in milk fat from cows fed hay while palmitic acid was highest from cows fed hay and haylage. These results suggest that type of forage fed may cause small changes in rumen fermentation and in milk composition. The importance of these changes is unknown but may affect properties of dairy products produced from this milk."} {"id": "PMID:1270653", "title": "Genetic parameters of several measures of milk flow rate and milking time.", "content": "Heritabilities and genetic correlations of milking rate, time, and yield were estimated by intrasire regression of daughter on dam for 252 Holstein pairs. Heritabilities were: lactation yield, .51 +/- .11; peak rate, .47 +/- .11; bucket milk yield, .38 +/- .10; average rate, .37 +/- .12; milk yield to .45 kg/min, .19 +/- .12; total time, .17 +/- .12; duration of peak rate, .10 +/- .10; strip time, .08 +/- .15; yield during peak rate, .07 +/- .11; and strip yield, .01 +/- .17. The genetic correlation of peak rate with lactation milk yield was .69 +/- .08, indicating substantial genetic improvement in milking rate by selecting for milk production. The genetic correlation between total milking time and lactation milk yield was .50 +/- .20, indicating an increase in total milking time due to selection for milk. Direct selection for peak rate would provide an opportunity to reduce total milking time.", "contents": "Genetic parameters of several measures of milk flow rate and milking time. Heritabilities and genetic correlations of milking rate, time, and yield were estimated by intrasire regression of daughter on dam for 252 Holstein pairs. Heritabilities were: lactation yield, .51 +/- .11; peak rate, .47 +/- .11; bucket milk yield, .38 +/- .10; average rate, .37 +/- .12; milk yield to .45 kg/min, .19 +/- .12; total time, .17 +/- .12; duration of peak rate, .10 +/- .10; strip time, .08 +/- .15; yield during peak rate, .07 +/- .11; and strip yield, .01 +/- .17. The genetic correlation of peak rate with lactation milk yield was .69 +/- .08, indicating substantial genetic improvement in milking rate by selecting for milk production. The genetic correlation between total milking time and lactation milk yield was .50 +/- .20, indicating an increase in total milking time due to selection for milk. Direct selection for peak rate would provide an opportunity to reduce total milking time."} {"id": "PMID:1270654", "title": "Social rank and physiological traits of dairy cows as influenced by changing group membership.", "content": "Social behavior was observed in two groups of 17 cows during 13 wk to determine dominance rank. On the basis of dominance ranking during two bi-weekly intervals (wk 3 and 4, 7 and 8), a total of six cows was exchanged between groups (two during the first and four during the second exchange). The effect on milk yield, milk leucocyte concentration, and milk prolactin of dominance rank and introduction of \"strange\" cows into a group was studied. Dominance rank was greater for older, heavier, taller cows in a later stage of lactation. Fat-corrected-milk yield was greater for dominant cows but milk prolactin was lower. Dominace rank for cows moved to a new group did not change appreciably. Persistency of milk yield was associated negatively with dominance rank for five of six exchanged cows. Since the average persistency of milk yield for all cows dropped 5% from wk 7 to wk 8, it appears exchange of cows between groups affected both exchanged and nonexchanged cows in a random manner. Neither dominance rank nor exchanging cows between groups had a significant effect on leucocyte concentrations in milk. Milk-prolactin concentrations were most highly correlated with dominance rank, stage of lactation, body weight, and height at withers.", "contents": "Social rank and physiological traits of dairy cows as influenced by changing group membership. Social behavior was observed in two groups of 17 cows during 13 wk to determine dominance rank. On the basis of dominance ranking during two bi-weekly intervals (wk 3 and 4, 7 and 8), a total of six cows was exchanged between groups (two during the first and four during the second exchange). The effect on milk yield, milk leucocyte concentration, and milk prolactin of dominance rank and introduction of \"strange\" cows into a group was studied. Dominance rank was greater for older, heavier, taller cows in a later stage of lactation. Fat-corrected-milk yield was greater for dominant cows but milk prolactin was lower. Dominace rank for cows moved to a new group did not change appreciably. Persistency of milk yield was associated negatively with dominance rank for five of six exchanged cows. Since the average persistency of milk yield for all cows dropped 5% from wk 7 to wk 8, it appears exchange of cows between groups affected both exchanged and nonexchanged cows in a random manner. Neither dominance rank nor exchanging cows between groups had a significant effect on leucocyte concentrations in milk. Milk-prolactin concentrations were most highly correlated with dominance rank, stage of lactation, body weight, and height at withers."} {"id": "PMID:1270655", "title": "Detection of estrus in dairy cows by electrical measurements of vaginal mucus and by milk progesterone.", "content": "Electrical resistance (ohms) of mucus were analyzed in 20 postpartum Holstein cows by use of a probe inserted into the anterior vagina every other day for 30 days. Composite milk samples were taken on the same day, and progesterone was determined by radioimmunoassay. Cows were observed twice daily for standing estrus and reproductive organs palpated weekly per rectum (rectal palpation). Fifteen cows which were cycling showed increasing progesterone 6 to 7 days after the onset of estrus with values of 8.1 to 10.0 ng progesterone/ml milk on days 10 to 17. Concentrations had declined rapidly 2 days before onset of the next estrus. Progesterone in milk was affected by cow and by day of the cycle. Electrical resistance followed a similar cyclical pattern, but variability was large and only cows differed. The correlation between milk progesterone and mucus resistance was .22. Progesterone concentrations for four cows with follicular cysts fluctuated randomly with a mean of 2.6 ng/ml. Mean resistance of vaginal mucus was 44 omega for both cycling and cystic cows, indicating that a single measurement of electrical resistance every 2nd day was unreliable in distinguishing physiological states. One cow had high progesterone in milk on days 19 to 25 and was diagnosed pregnant by rectal palpation 3 wk later. Cows were not seen in estrus 28% of the time when milk progesterone and rectal palpation indicated they were in the follicular phase of the estrous cycle and were cycling.", "contents": "Detection of estrus in dairy cows by electrical measurements of vaginal mucus and by milk progesterone. Electrical resistance (ohms) of mucus were analyzed in 20 postpartum Holstein cows by use of a probe inserted into the anterior vagina every other day for 30 days. Composite milk samples were taken on the same day, and progesterone was determined by radioimmunoassay. Cows were observed twice daily for standing estrus and reproductive organs palpated weekly per rectum (rectal palpation). Fifteen cows which were cycling showed increasing progesterone 6 to 7 days after the onset of estrus with values of 8.1 to 10.0 ng progesterone/ml milk on days 10 to 17. Concentrations had declined rapidly 2 days before onset of the next estrus. Progesterone in milk was affected by cow and by day of the cycle. Electrical resistance followed a similar cyclical pattern, but variability was large and only cows differed. The correlation between milk progesterone and mucus resistance was .22. Progesterone concentrations for four cows with follicular cysts fluctuated randomly with a mean of 2.6 ng/ml. Mean resistance of vaginal mucus was 44 omega for both cycling and cystic cows, indicating that a single measurement of electrical resistance every 2nd day was unreliable in distinguishing physiological states. One cow had high progesterone in milk on days 19 to 25 and was diagnosed pregnant by rectal palpation 3 wk later. Cows were not seen in estrus 28% of the time when milk progesterone and rectal palpation indicated they were in the follicular phase of the estrous cycle and were cycling."} {"id": "PMID:1270656", "title": "Ration digestibility and mineral balance in lactating cows fed rations containing dried whey.", "content": "Including dried whey in rations of nonruminants usually increases digestibilities and mineral retention, presumably because of the lactose in the whey. A trial with total collection had five lactating cows per treatment to determine the effects of 5% dried whey product in the concentrate on digestibility of the ration and on absorption and retention of calcium, magnesium, and phosphorus. Rations included corn silage ad libitum, 3 kg alfalfa hay, and either control or dried whey product in concentrate ration at 1 kg/3 kg milk produced. Rations were balanced for content of nitrogen, calcium, magnesium, and phosphorus. Digestibilities of dry matter, nitrogen, and energy were not increased with dried whey product in the ration. Apparent absorption of calcium, magnesium, and phosphorus was not affected significantly by inclusion of whey in the ration. Productive (milk plus retained) calcium and magnesium were not increased when dried whey product was in the ration although productive phosphorus was slightly higher with the dried whey product. Adding small amounts of dried whey to a ruminant's ration will not increase mineral absorption and retention probably because tthe lactose in dried whey is fermented in the rumen and unavailabe for aiding absorption from the small intestine.", "contents": "Ration digestibility and mineral balance in lactating cows fed rations containing dried whey. Including dried whey in rations of nonruminants usually increases digestibilities and mineral retention, presumably because of the lactose in the whey. A trial with total collection had five lactating cows per treatment to determine the effects of 5% dried whey product in the concentrate on digestibility of the ration and on absorption and retention of calcium, magnesium, and phosphorus. Rations included corn silage ad libitum, 3 kg alfalfa hay, and either control or dried whey product in concentrate ration at 1 kg/3 kg milk produced. Rations were balanced for content of nitrogen, calcium, magnesium, and phosphorus. Digestibilities of dry matter, nitrogen, and energy were not increased with dried whey product in the ration. Apparent absorption of calcium, magnesium, and phosphorus was not affected significantly by inclusion of whey in the ration. Productive (milk plus retained) calcium and magnesium were not increased when dried whey product was in the ration although productive phosphorus was slightly higher with the dried whey product. Adding small amounts of dried whey to a ruminant's ration will not increase mineral absorption and retention probably because tthe lactose in dried whey is fermented in the rumen and unavailabe for aiding absorption from the small intestine."} {"id": "PMID:1270695", "title": "Sex-typed play in feminoid boys versus normal boys and girls.", "content": "Procedures for assessing children's sex-typed play were developed which (a) examined children's continuous play in four sessions totaling 20 minutes rather than measuring only initial choice of a sex-typed toy, and (b) did not impose the stimulus-specific condition of requiring an adult experimenter to be present to administer the task. Play with \"masculine\" and \"feminine\" toys was observed for 120 normal children (60 boys, 60 girls) aged 3 yr.-8 yr., and 15 similarly aged boys diagnosed as having childhood gender disturbance. Significant differences were found in the sex-typed play of the two normal groups, but no age differences were observed. The amount of feminine play by the feminoid boys was found to be significantly greater than that of normal boys, but not significantly different from the predominantly feminine play patterns of the normal girls. The usefulness of such a measure for the clinical assessment of deviant sex-role development in young children is discussed.", "contents": "Sex-typed play in feminoid boys versus normal boys and girls. Procedures for assessing children's sex-typed play were developed which (a) examined children's continuous play in four sessions totaling 20 minutes rather than measuring only initial choice of a sex-typed toy, and (b) did not impose the stimulus-specific condition of requiring an adult experimenter to be present to administer the task. Play with \"masculine\" and \"feminine\" toys was observed for 120 normal children (60 boys, 60 girls) aged 3 yr.-8 yr., and 15 similarly aged boys diagnosed as having childhood gender disturbance. Significant differences were found in the sex-typed play of the two normal groups, but no age differences were observed. The amount of feminine play by the feminoid boys was found to be significantly greater than that of normal boys, but not significantly different from the predominantly feminine play patterns of the normal girls. The usefulness of such a measure for the clinical assessment of deviant sex-role development in young children is discussed."} {"id": "PMID:1270696", "title": "Behavior problems in elementary school children a follow-up study.", "content": "Two-year follow-up data for an ostensibly normal sample of children who had been previously characterized on a number of behavior problem dimensions by their teachers and peers were analyzed. In addition, 1-year follow-up data were presented for a group of extreme behavior children from the same school. The behavior dimensions of Distractibility and Conduct Problem were fairly stable over 2 years for girls and boys. In addition, Inadequacy-Immaturity was stable for girls and may mark more severe behavior problems for young girls. Behavior problems of young girls were more predictive of later achievement difficulties while behavior problems of boys were more predictive of peer and teacher difficulty. Finally, teacher's clinical judgement was demonstrated to be useful for indexing behavior for hyperactive boys.", "contents": "Behavior problems in elementary school children a follow-up study. Two-year follow-up data for an ostensibly normal sample of children who had been previously characterized on a number of behavior problem dimensions by their teachers and peers were analyzed. In addition, 1-year follow-up data were presented for a group of extreme behavior children from the same school. The behavior dimensions of Distractibility and Conduct Problem were fairly stable over 2 years for girls and boys. In addition, Inadequacy-Immaturity was stable for girls and may mark more severe behavior problems for young girls. Behavior problems of young girls were more predictive of later achievement difficulties while behavior problems of boys were more predictive of peer and teacher difficulty. Finally, teacher's clinical judgement was demonstrated to be useful for indexing behavior for hyperactive boys."} {"id": "PMID:1270697", "title": "The ecological assessment of an autistic child.", "content": "The behavior of an autistic child was observed in his natural environment. Observations were made in three settings, over approximately 6 months. Sixteen behaviors of the child and six behaviors of adults and peers were recorded. A cluster analysis was performed to identify response classes within the behavioral structure of the child and to see if correlations existed between response and stimulus events. To examine intra- and intersetting changes, Spearman rank correlations and t tests were also computed. The autistic child exhibited a diversity of behavior over time in a given setting and across settings. He persistently ignored other nonautistic children, although he was responsive to adults. Response classes reflected an inverse correlation between the child's self-stimulatory behaviors and his attentiveness to the environment. Elevated levels of adult attention were consistently related to reduced levels in most self-stimulatory behaviors. Two response classes showed inverse relationships between self-stimulatory behaviors. Reducing the frequency of some self-stimulatory behaviors might cause increases in others.", "contents": "The ecological assessment of an autistic child. The behavior of an autistic child was observed in his natural environment. Observations were made in three settings, over approximately 6 months. Sixteen behaviors of the child and six behaviors of adults and peers were recorded. A cluster analysis was performed to identify response classes within the behavioral structure of the child and to see if correlations existed between response and stimulus events. To examine intra- and intersetting changes, Spearman rank correlations and t tests were also computed. The autistic child exhibited a diversity of behavior over time in a given setting and across settings. He persistently ignored other nonautistic children, although he was responsive to adults. Response classes reflected an inverse correlation between the child's self-stimulatory behaviors and his attentiveness to the environment. Elevated levels of adult attention were consistently related to reduced levels in most self-stimulatory behaviors. Two response classes showed inverse relationships between self-stimulatory behaviors. Reducing the frequency of some self-stimulatory behaviors might cause increases in others."} {"id": "PMID:1270698", "title": "Attributional change and the importance of baseline recording a case illustration.", "content": "This single case study illustrates how attention to baseline measures prevented premature conclusions regarding the impact of a conditioning procedure upon aggressive, acting-out behavior. Five disruptive behaviors were initially delineated so that frequency distributions could be obtained. During the course of this 15-day observational period, a significant reduction in the number of these aggressive responses was noted. The proposed conditioning procedure was therefore never required. Explanations as well as implications regarding the observed alteration in behavior were discussed.", "contents": "Attributional change and the importance of baseline recording a case illustration. This single case study illustrates how attention to baseline measures prevented premature conclusions regarding the impact of a conditioning procedure upon aggressive, acting-out behavior. Five disruptive behaviors were initially delineated so that frequency distributions could be obtained. During the course of this 15-day observational period, a significant reduction in the number of these aggressive responses was noted. The proposed conditioning procedure was therefore never required. Explanations as well as implications regarding the observed alteration in behavior were discussed."} {"id": "PMID:1270699", "title": "Some detrimental effects of using extra stimuli to guide learning in normal and autistic children.", "content": "This study was designed to assess the effectiveness of using prompts (extra \"guiding\" stimuli) for teaching normal and autistic children. One group of normal children was pretrained on a color discrimination. Later, the colors were used as prompts (presented simultaneously with new training stimuli) to teach four new discriminations. Another group of normal children was trained on the same discriminations with a trial-and-error procedure (i.e., no prompting). A third group consisted of autistic children who were trained on these discriminations using the prompt procedure. Analyses of the results showed the following. (1) The trial-and-error group of normal children acquired more discriminations than the prompt group of normal children. (2) A comparison of the two prompt groups showed that the autistics failed to transfer from the prompt cue to the training cue more often than the normal children; rather, the autistics generally continued responding to the faded color cue. (3) Autistic and normal children who failed to acquire the discriminations when trained with a prompt procedure did acquire these discriminations when no prompt was used. That is, the results suggest that the presentation of an extra guiding stimulus was detrimental to the acquisition of training discriminations for all subjects, and particularly so far autistic children. Therefore, the common practice of providing extra guiding stimuli in proportion to the severity of the learning disorder may actually be harmful to the learning of new skills. Implications of these results for future research are discussed.", "contents": "Some detrimental effects of using extra stimuli to guide learning in normal and autistic children. This study was designed to assess the effectiveness of using prompts (extra \"guiding\" stimuli) for teaching normal and autistic children. One group of normal children was pretrained on a color discrimination. Later, the colors were used as prompts (presented simultaneously with new training stimuli) to teach four new discriminations. Another group of normal children was trained on the same discriminations with a trial-and-error procedure (i.e., no prompting). A third group consisted of autistic children who were trained on these discriminations using the prompt procedure. Analyses of the results showed the following. (1) The trial-and-error group of normal children acquired more discriminations than the prompt group of normal children. (2) A comparison of the two prompt groups showed that the autistics failed to transfer from the prompt cue to the training cue more often than the normal children; rather, the autistics generally continued responding to the faded color cue. (3) Autistic and normal children who failed to acquire the discriminations when trained with a prompt procedure did acquire these discriminations when no prompt was used. That is, the results suggest that the presentation of an extra guiding stimulus was detrimental to the acquisition of training discriminations for all subjects, and particularly so far autistic children. Therefore, the common practice of providing extra guiding stimuli in proportion to the severity of the learning disorder may actually be harmful to the learning of new skills. Implications of these results for future research are discussed."} {"id": "PMID:1270700", "title": "Comparison of the WISC and WISC-R on a psychiatric adolescent impatient sample.", "content": "The present study compared the WISC and WISC-R on a group of psychiatric adolescent inpatients. The results indicated high intercorrelationss between the two test versions but with the correlation linearly related to the changes in content and administration rules of the WISC-R. Analyses of variance indicated that, on the basis of the Full Scale IQ, the WISC is an \"easier\" test than the WISC-R.", "contents": "Comparison of the WISC and WISC-R on a psychiatric adolescent impatient sample. The present study compared the WISC and WISC-R on a group of psychiatric adolescent inpatients. The results indicated high intercorrelationss between the two test versions but with the correlation linearly related to the changes in content and administration rules of the WISC-R. Analyses of variance indicated that, on the basis of the Full Scale IQ, the WISC is an \"easier\" test than the WISC-R."} {"id": "PMID:1270713", "title": "Nutrition education for medical students. I. What is it? Where has it been? Why should it be taught?", "content": "After an eight-year experience of introducing nutrition into the medical school curriculum of a new medical school, the author reflects on the state of the art. Questions are raised: What is nutrition? Is it part of medical education? If not, why not? Why should it be taught? The article ends with a note of optimism with reference to nutrition education in medical schools.", "contents": "Nutrition education for medical students. I. What is it? Where has it been? Why should it be taught? After an eight-year experience of introducing nutrition into the medical school curriculum of a new medical school, the author reflects on the state of the art. Questions are raised: What is nutrition? Is it part of medical education? If not, why not? Why should it be taught? The article ends with a note of optimism with reference to nutrition education in medical schools."} {"id": "PMID:1270714", "title": "Nutrition education for medical students. II. Who shall teach it? Within what framework? How?", "content": "There exists inadequate recognition, inadequate support, and inadequate attention to the subject of nutrion in medical schools. While progress has occurred in some schools, the teaching of nutrition has not generally been integrated into the curriculum of the medical school. This paper raises the question: Within what framework and how? The author attempts to highlight the role of the nutrition educator in the medical center setting as the health professional to assume leadership. There are signs of renewed interest. Efforts are being made to expand nutritional knowledge in the medical school curriculum. The design of nutrition in the curriculum must reflect the needs of society and of the learner. There must be relevance. The program must be problem-centered, affording the learners the opportunities to engage in the discovery of the role of nutrition in the health of people, the nutritional environment, and the interplay between the two.", "contents": "Nutrition education for medical students. II. Who shall teach it? Within what framework? How? There exists inadequate recognition, inadequate support, and inadequate attention to the subject of nutrion in medical schools. While progress has occurred in some schools, the teaching of nutrition has not generally been integrated into the curriculum of the medical school. This paper raises the question: Within what framework and how? The author attempts to highlight the role of the nutrition educator in the medical center setting as the health professional to assume leadership. There are signs of renewed interest. Efforts are being made to expand nutritional knowledge in the medical school curriculum. The design of nutrition in the curriculum must reflect the needs of society and of the learner. There must be relevance. The program must be problem-centered, affording the learners the opportunities to engage in the discovery of the role of nutrition in the health of people, the nutritional environment, and the interplay between the two."} {"id": "PMID:1270715", "title": "Zinc content of selected foods.", "content": "The zinc content of 174 foods was determined by atomic absorption spectrophotometry, using a dry ash preparation method. Data on some of the foods were not available elsewhere. Shellfish, cheese, meats, and nuts represented the highest sources of zinc found in this study. Soft drinks and other beverages, as well as vegetables generally, were poor sources of zinc.", "contents": "Zinc content of selected foods. The zinc content of 174 foods was determined by atomic absorption spectrophotometry, using a dry ash preparation method. Data on some of the foods were not available elsewhere. Shellfish, cheese, meats, and nuts represented the highest sources of zinc found in this study. Soft drinks and other beverages, as well as vegetables generally, were poor sources of zinc."} {"id": "PMID:1270716", "title": "Menu planning in the Nutrition Program for the Elderly. Modified Nutrient Standard Menu method.", "content": "A nutrient standard menu (NSM) planning method was developed for use in planning menus which provided one-third the Recommended Dietary Allowances for persons sixty years of age or older for nine indicator nutrients and calories, while restricting fat to less than 40 per cent of total calories. To eliminate manual calculations and make it easy for individuals untrained in dietetics or nutrition to use NSM planning, the nutrient composition of over a thousand commonly used menu items was listed in a menu planning manual in nutrient units which were one-tenth of the nutrient standard for the meal. Menus from third-party sources were monitored by selecting similar nutritionally analyzed menu items in the manual and adjusting the nutrient composition to conform to the portions actually served. Ten site managers of the Administration on Aging (AoA) evaluated the planning/monitoring method. The members of the group, on the average, were fifty-six years of age, had 1.6 years of education beyond high school, and had 4.6 years of foodservice experience. Approximately 83 per cent of the evaluators did not plan to monitor menus at their sites and had no formal training in dietetics or nutrition. Eighty-four per cent were able to plan menus satisfactorily after this brief introduction. The younger evaluators with more education grasped the concepts faster and were able to plan menus with greater accuracy. The data also indicated that previous experience in menu planning enhanced their ability to plan NSMs. Most felt the approach to be workable and applicable. Menu monitoring was more difficult for the evaluators. Seventy-five per cent were able to monitor menus satisfactorily, and all felt they could do so with more time. The data again showed that the younger individuals having more formal education were able to master the monitoring skills more easily.", "contents": "Menu planning in the Nutrition Program for the Elderly. Modified Nutrient Standard Menu method. A nutrient standard menu (NSM) planning method was developed for use in planning menus which provided one-third the Recommended Dietary Allowances for persons sixty years of age or older for nine indicator nutrients and calories, while restricting fat to less than 40 per cent of total calories. To eliminate manual calculations and make it easy for individuals untrained in dietetics or nutrition to use NSM planning, the nutrient composition of over a thousand commonly used menu items was listed in a menu planning manual in nutrient units which were one-tenth of the nutrient standard for the meal. Menus from third-party sources were monitored by selecting similar nutritionally analyzed menu items in the manual and adjusting the nutrient composition to conform to the portions actually served. Ten site managers of the Administration on Aging (AoA) evaluated the planning/monitoring method. The members of the group, on the average, were fifty-six years of age, had 1.6 years of education beyond high school, and had 4.6 years of foodservice experience. Approximately 83 per cent of the evaluators did not plan to monitor menus at their sites and had no formal training in dietetics or nutrition. Eighty-four per cent were able to plan menus satisfactorily after this brief introduction. The younger evaluators with more education grasped the concepts faster and were able to plan menus with greater accuracy. The data also indicated that previous experience in menu planning enhanced their ability to plan NSMs. Most felt the approach to be workable and applicable. Menu monitoring was more difficult for the evaluators. Seventy-five per cent were able to monitor menus satisfactorily, and all felt they could do so with more time. The data again showed that the younger individuals having more formal education were able to master the monitoring skills more easily."} {"id": "PMID:1270717", "title": "Dietary intake and coronary risk factors in Peruvian Quechua Indians.", "content": "Some of the \"risk\" factors implicated in the etiology of coronary atherosclerotic heart disease were investigated in sixty Quechua men living in two areas of Peru. Highland Quechua had higher serum triglycerides (mean, 122 vs. 90 mg. per deciliter) than downward migrants. There were no significant differences between the two groups in serum cholesterol (mean 150 vs. 157 mg. per deciliter), body fat (mean, 15 vs. 17%), or blood pressure (mean, 113/72 vs. 114/72 mm Hg). Both groups consumed about 2,500 kcal per man per day, while the highland Quechua consumed more carbohydrate (mean, 66 vs. 51%) and less fat (mean 19 vs. 33%). By American standards, both groups had low serum cholesterol values, as well as low blood pressure.", "contents": "Dietary intake and coronary risk factors in Peruvian Quechua Indians. Some of the \"risk\" factors implicated in the etiology of coronary atherosclerotic heart disease were investigated in sixty Quechua men living in two areas of Peru. Highland Quechua had higher serum triglycerides (mean, 122 vs. 90 mg. per deciliter) than downward migrants. There were no significant differences between the two groups in serum cholesterol (mean 150 vs. 157 mg. per deciliter), body fat (mean, 15 vs. 17%), or blood pressure (mean, 113/72 vs. 114/72 mm Hg). Both groups consumed about 2,500 kcal per man per day, while the highland Quechua consumed more carbohydrate (mean, 66 vs. 51%) and less fat (mean 19 vs. 33%). By American standards, both groups had low serum cholesterol values, as well as low blood pressure."} {"id": "PMID:1270718", "title": "Effects on pregnant adolescents of attending a special school.", "content": "Data on nutrient intakes and blood vitamin levels were obtained for twenty-nine pregnant adolescents attending a special school for pregnant school-age girls in New Brunswick, New Jersey. Except for calcium and iron, mean intakes were equal to or greater than the Recommended Dietary Allowances. Food eaten at school contributed 35 to 43% of the total nutrient intake. Mean blood vitamin levels were normal to high, although about a fourth of the girls had low levels of vitamin B6 and folate. All except one delivered normal, full-term infants. It was concluded that attendance at such a special school contributes to normal pregnancy outcome among teen-age mothers.", "contents": "Effects on pregnant adolescents of attending a special school. Data on nutrient intakes and blood vitamin levels were obtained for twenty-nine pregnant adolescents attending a special school for pregnant school-age girls in New Brunswick, New Jersey. Except for calcium and iron, mean intakes were equal to or greater than the Recommended Dietary Allowances. Food eaten at school contributed 35 to 43% of the total nutrient intake. Mean blood vitamin levels were normal to high, although about a fourth of the girls had low levels of vitamin B6 and folate. All except one delivered normal, full-term infants. It was concluded that attendance at such a special school contributes to normal pregnancy outcome among teen-age mothers."} {"id": "PMID:1270719", "title": "Health food users in two Texas cities. Nutritional and socioeconomic implications.", "content": "Health food buyers--both casual purchasers and confirmed customers of health food stores--were surveyed in Dallas and Houston. In both groups, users were generally in the middle class economically and in the active productive age brackets. Users in lower income groups spent larger proportions of their food budget in health food stores. The majority of confirmed users did so in the belief that such foods would provide health benefits, as health food proponents claim. Sixty-six per cent of the general public reported using vitamin and mineral supplements, compared with 93% of the confirmed health food users; the latter usually bought their supplements in health food stores, where megavitamins are likely to be promoted. Users among the general public, on the other hand, purchased supplements in drug stores and supermarkets as a rule.", "contents": "Health food users in two Texas cities. Nutritional and socioeconomic implications. Health food buyers--both casual purchasers and confirmed customers of health food stores--were surveyed in Dallas and Houston. In both groups, users were generally in the middle class economically and in the active productive age brackets. Users in lower income groups spent larger proportions of their food budget in health food stores. The majority of confirmed users did so in the belief that such foods would provide health benefits, as health food proponents claim. Sixty-six per cent of the general public reported using vitamin and mineral supplements, compared with 93% of the confirmed health food users; the latter usually bought their supplements in health food stores, where megavitamins are likely to be promoted. Users among the general public, on the other hand, purchased supplements in drug stores and supermarkets as a rule."} {"id": "PMID:1270722", "title": "Immunity and survival.", "content": "Studies in human families and in surviving older persons suggest that the immune system may have an important role in the control of the survival. Immune response (Ir) genes to infectious agents can be detected in human families.", "contents": "Immunity and survival. Studies in human families and in surviving older persons suggest that the immune system may have an important role in the control of the survival. Immune response (Ir) genes to infectious agents can be detected in human families."} {"id": "PMID:1270723", "title": "Mortality fluctuations among chronically ill medical geriatric patients as an indicator of stress before and after relocation.", "content": "The effects of mass transfer of a sick geriatric population of war veterans were evaluated to determine the resultant change in mortality. A comparison of mortality patterns by months during this interval made over a six-year period, centered around the month of the move, July 1971. Analysis of the mortality fluctuations in the 24-month interval surrounding the move indicated that the course of mortality during this interval was periodic, with four distinguishable phases making up the complete cycle. An attempt was made to link stress-inducing events before, during and after the relocation with the ensuing mortality. It is important to use planned, low-key, stress-prevention measures and continue them for some time after the move, to offset adverse mortality effects from anticipatory anxiety and from the postrelocation release of anxiety-generated stress.", "contents": "Mortality fluctuations among chronically ill medical geriatric patients as an indicator of stress before and after relocation. The effects of mass transfer of a sick geriatric population of war veterans were evaluated to determine the resultant change in mortality. A comparison of mortality patterns by months during this interval made over a six-year period, centered around the month of the move, July 1971. Analysis of the mortality fluctuations in the 24-month interval surrounding the move indicated that the course of mortality during this interval was periodic, with four distinguishable phases making up the complete cycle. An attempt was made to link stress-inducing events before, during and after the relocation with the ensuing mortality. It is important to use planned, low-key, stress-prevention measures and continue them for some time after the move, to offset adverse mortality effects from anticipatory anxiety and from the postrelocation release of anxiety-generated stress."} {"id": "PMID:1270724", "title": "Involuntary transfer as a cause of death and a medical hospitalization in geriatric neuropsychiatric patients.", "content": "The effects of mass involuntary transfer on geriatric neuropsychiatric male patients were evaluated by comparing outcomes for three overlapping sets of patients (N = 403, 385, and 378) over several follow-up periods. One group, the \"reorganization\" sample, consisted of all patients on three geriatric wards at a time just before the wards were reorganized and 20 percent of the patients were transferred to other buildings. The comparison samples comprised two overlapping groups consisting of all patients on the wards four months earlier and four months later.", "contents": "Involuntary transfer as a cause of death and a medical hospitalization in geriatric neuropsychiatric patients. The effects of mass involuntary transfer on geriatric neuropsychiatric male patients were evaluated by comparing outcomes for three overlapping sets of patients (N = 403, 385, and 378) over several follow-up periods. One group, the \"reorganization\" sample, consisted of all patients on three geriatric wards at a time just before the wards were reorganized and 20 percent of the patients were transferred to other buildings. The comparison samples comprised two overlapping groups consisting of all patients on the wards four months earlier and four months later."} {"id": "PMID:1270755", "title": "Large scale production, purification and a study of some spectral properties of Penitrem A.", "content": "A large scale production of the tremorgenic toxin, Penitrem A, from the cultures of Penicillium (P.) palitans and P. crustosum for studying its spectral characteristics was attained. From several fermentation runs using Czapex-Dox medium, P. crustosum was shown to produce nearly 80% more toxic metabolite than P. palitans. A method involving silica-gel column chromatography for a single step isolation of the toxin from the crude extract of the mycelial mats was developed. Some spectral properties of Penitrem A were discussed.", "contents": "Large scale production, purification and a study of some spectral properties of Penitrem A. A large scale production of the tremorgenic toxin, Penitrem A, from the cultures of Penicillium (P.) palitans and P. crustosum for studying its spectral characteristics was attained. From several fermentation runs using Czapex-Dox medium, P. crustosum was shown to produce nearly 80% more toxic metabolite than P. palitans. A method involving silica-gel column chromatography for a single step isolation of the toxin from the crude extract of the mycelial mats was developed. Some spectral properties of Penitrem A were discussed."} {"id": "PMID:1270756", "title": "A flame ionisation detector for the determination of nitrix oxide.", "content": "Existing methods for the detection of nitric oxide are described, and their detection limits noted. The use of a flame ionisation detector is proposed, and the means by which its sensitivity toward nitrix oxide can be greatly enhanced is described. Detector operating conditions and response characteristics are given.", "contents": "A flame ionisation detector for the determination of nitrix oxide. Existing methods for the detection of nitric oxide are described, and their detection limits noted. The use of a flame ionisation detector is proposed, and the means by which its sensitivity toward nitrix oxide can be greatly enhanced is described. Detector operating conditions and response characteristics are given."} {"id": "PMID:1270757", "title": "2,4-D levels in the South Saskatchewan River in 1973 as determined by GLC method.", "content": "2,4-D levels in the South Saskatchewan River near Saskatoon in 1973 at the height of the spraying season, and at harvestime, were determined by a method involving direct glc analysis, ankaline hydrolysis, followed by n-butylation of the liberated free acid after acidification of the alkaline solution, and confirmed by subsequent n-octylation. GC/MS also confirmed the presence of 2,4-D. 2,4-D was detected during the spraying season but not at harvest time or in river mud samples. The average level was ca. 2mug of acid equivalent to 2,4-D per liter of river water at the height of the spraying season.", "contents": "2,4-D levels in the South Saskatchewan River in 1973 as determined by GLC method. 2,4-D levels in the South Saskatchewan River near Saskatoon in 1973 at the height of the spraying season, and at harvestime, were determined by a method involving direct glc analysis, ankaline hydrolysis, followed by n-butylation of the liberated free acid after acidification of the alkaline solution, and confirmed by subsequent n-octylation. GC/MS also confirmed the presence of 2,4-D. 2,4-D was detected during the spraying season but not at harvest time or in river mud samples. The average level was ca. 2mug of acid equivalent to 2,4-D per liter of river water at the height of the spraying season."} {"id": "PMID:1270758", "title": "Chemical transformation of S-benzyl O-ethyl phenylphosphonothiolate (Inezin) by ultraviolet light.", "content": "The photodecomposition of Inezin (S-benzyl O-ethyl phenylphosphonothiolate) in n-hexane under the ultraviiolet irradiation was investigated by gas liquid chromatography, thin layer chromatography, mass spectrometry, and infrared spectroscopy. Two main steps of photodecomposition were observed at the initial stage of irradiation. One was the cleavage of P-S bond to produce O-ethyl phenylphosphinate and dibenzyl disulfide, the latter of which was degraded rather rapidly to produce sulfuric acid and benzoic acid through toluene-alpha-sulfonic acid by oxidation. The other step was the isomerization to the thionate, O-benzyl O-ethyl phenylphosphonothionate, which was gradually oxidized to itx oxygen analogue, O-benzyl O-ethyl phenylphosphate. O-ethyl phenylphosphinate, O-benzyl O-ethyl phenylphosphonate and O-benzyl O-ethyl phenylphosphonthionate were fairly stable under the ultraviolet light, as compared with Inezin. As hydrolysis products of the parent compound, phenylphosphonic acid, O-ethyl hydrogen phenylphosphonate, O-ethyl hydrogen phenylphosphonothioate and benzyl alcohol were detected.", "contents": "Chemical transformation of S-benzyl O-ethyl phenylphosphonothiolate (Inezin) by ultraviolet light. The photodecomposition of Inezin (S-benzyl O-ethyl phenylphosphonothiolate) in n-hexane under the ultraviiolet irradiation was investigated by gas liquid chromatography, thin layer chromatography, mass spectrometry, and infrared spectroscopy. Two main steps of photodecomposition were observed at the initial stage of irradiation. One was the cleavage of P-S bond to produce O-ethyl phenylphosphinate and dibenzyl disulfide, the latter of which was degraded rather rapidly to produce sulfuric acid and benzoic acid through toluene-alpha-sulfonic acid by oxidation. The other step was the isomerization to the thionate, O-benzyl O-ethyl phenylphosphonothionate, which was gradually oxidized to itx oxygen analogue, O-benzyl O-ethyl phenylphosphate. O-ethyl phenylphosphinate, O-benzyl O-ethyl phenylphosphonate and O-benzyl O-ethyl phenylphosphonthionate were fairly stable under the ultraviolet light, as compared with Inezin. As hydrolysis products of the parent compound, phenylphosphonic acid, O-ethyl hydrogen phenylphosphonate, O-ethyl hydrogen phenylphosphonothioate and benzyl alcohol were detected."} {"id": "PMID:1270759", "title": "Influence of diet and feed restriction on kidney function of aging male rats.", "content": "The influence of diet and feed restriction on kidney function was studied in aging male albino rats. Rats were fed either a commercial feed (LB) or a modified human diet (MHD) from weaning until sacrifice at either 12 or 24 mo. of age. Restricted rats were fed for only 15 out of each 48 hours. Feed restriction during either the first, the second, or both years of life was beneficial in delaying age-associated changes in kidney function as indicated by decreased proteinuria, increased in vitro transport of paraaminohippuric acid, and reduced incidence and severity of renal lesions. Urinary creatinine and blood urea nitrogen levels were also favorably influenced by restriction. Most parameters were modified by diet as well as by restriction, with MHD being generally associated with improved kidney function. Improvement in kidney function may have been more related to a reduction in protein intake than to a reduction in caloric intake as a whole.", "contents": "Influence of diet and feed restriction on kidney function of aging male rats. The influence of diet and feed restriction on kidney function was studied in aging male albino rats. Rats were fed either a commercial feed (LB) or a modified human diet (MHD) from weaning until sacrifice at either 12 or 24 mo. of age. Restricted rats were fed for only 15 out of each 48 hours. Feed restriction during either the first, the second, or both years of life was beneficial in delaying age-associated changes in kidney function as indicated by decreased proteinuria, increased in vitro transport of paraaminohippuric acid, and reduced incidence and severity of renal lesions. Urinary creatinine and blood urea nitrogen levels were also favorably influenced by restriction. Most parameters were modified by diet as well as by restriction, with MHD being generally associated with improved kidney function. Improvement in kidney function may have been more related to a reduction in protein intake than to a reduction in caloric intake as a whole."} {"id": "PMID:1270760", "title": "Experimental allergic encephalomyelitis in aged F344 rats.", "content": "Experimental allergic encephalomyelitis (EAE) was produced in 2- to 24-mo.-old F344 rats by active immunization and by passive transfer of lymphoid cells (adoptive immunization) from young rats. With both methods, some 24-mo.-old rats had a reduced ability to develop this autoimmune disease. However, the immunological deficit was related to incidental serious diseases rather than to old age per se. The aged F344 rat is not a suitable model for comparing EAE to multiple sclerosis in man because the decreased incidence of multiple sclerosis after the age of 50 is not related to other serious illnesses.", "contents": "Experimental allergic encephalomyelitis in aged F344 rats. Experimental allergic encephalomyelitis (EAE) was produced in 2- to 24-mo.-old F344 rats by active immunization and by passive transfer of lymphoid cells (adoptive immunization) from young rats. With both methods, some 24-mo.-old rats had a reduced ability to develop this autoimmune disease. However, the immunological deficit was related to incidental serious diseases rather than to old age per se. The aged F344 rat is not a suitable model for comparing EAE to multiple sclerosis in man because the decreased incidence of multiple sclerosis after the age of 50 is not related to other serious illnesses."} {"id": "PMID:1270761", "title": "Depression in the elderly.", "content": "Depressions in the elderly have many similarities to depressions in other age groups, particularly in their episodic nature, their tendency to remit, and their potential for favorable immediate outcome. They may, however, be far more easily overlooked. They often are considered to be consistent with senescence because of their frequent association with metabolic disturbance, with a variety of physical illnesses, with impaired cerebral function, and with hypochondriacal manifestations that may be viewed as characteristic of old age. It is important, therefore, that the clinician who treats these older patients be aware that depression is the psychiatric symptom he will most often encounter in the elderly and that it is as distressing in this age group as it is in younger persons. It represents an entity that often is reversible with prompt and appropriate treatment.", "contents": "Depression in the elderly. Depressions in the elderly have many similarities to depressions in other age groups, particularly in their episodic nature, their tendency to remit, and their potential for favorable immediate outcome. They may, however, be far more easily overlooked. They often are considered to be consistent with senescence because of their frequent association with metabolic disturbance, with a variety of physical illnesses, with impaired cerebral function, and with hypochondriacal manifestations that may be viewed as characteristic of old age. It is important, therefore, that the clinician who treats these older patients be aware that depression is the psychiatric symptom he will most often encounter in the elderly and that it is as distressing in this age group as it is in younger persons. It represents an entity that often is reversible with prompt and appropriate treatment."} {"id": "PMID:1270762", "title": "The comparative frequency of depression in various adult age groups.", "content": "This paper reviews some methodological problems in assessing the age distribution of depression, catalogues and summarizes the findings of various epidemiological surveys, and discusses the implications of these findings from the view point of public health, clinical diagnosis, and research into the etiology of depression.", "contents": "The comparative frequency of depression in various adult age groups. This paper reviews some methodological problems in assessing the age distribution of depression, catalogues and summarizes the findings of various epidemiological surveys, and discusses the implications of these findings from the view point of public health, clinical diagnosis, and research into the etiology of depression."} {"id": "PMID:1270763", "title": "Age differentiation in depression: biochemical aspects.", "content": "No age is immune to depression but the elderly seem especially susceptible since the incidence and prevalence is highest in the age group 55-70. At all ages the causes of depression are multiple and not fully understood. Elderly people who have been prone to depression earlier in life are especially vulnerable to major life stresses but the incidence rises even among those who have not had depressions earlier in life. Evidence based largely upon the mechanism of action of drugs specifically therapeutic for depression suggests that depression is associated with alterations in the synthesis, storage, release, and utilization of chemical neurotransmitters. Enzymes involved in these mechanisms are under genetic control. Furthermore, alterations in the activity of these enzymes occur with aging. The interaction of these biological and psychosocial changes relates to increased depression in the elderly. Treatment with tricyclic antidepressants is usually effective but must be reinforced with appropriate environmental support systems.", "contents": "Age differentiation in depression: biochemical aspects. No age is immune to depression but the elderly seem especially susceptible since the incidence and prevalence is highest in the age group 55-70. At all ages the causes of depression are multiple and not fully understood. Elderly people who have been prone to depression earlier in life are especially vulnerable to major life stresses but the incidence rises even among those who have not had depressions earlier in life. Evidence based largely upon the mechanism of action of drugs specifically therapeutic for depression suggests that depression is associated with alterations in the synthesis, storage, release, and utilization of chemical neurotransmitters. Enzymes involved in these mechanisms are under genetic control. Furthermore, alterations in the activity of these enzymes occur with aging. The interaction of these biological and psychosocial changes relates to increased depression in the elderly. Treatment with tricyclic antidepressants is usually effective but must be reinforced with appropriate environmental support systems."} {"id": "PMID:1270764", "title": "The age factor in depressive illness: some genetic considerations.", "content": "The age of onset of depressive illness may have an association with the genetic character and clinical course of the disorder. There are several genetic models of depressive disorder that are based on differences in age of onset. According to a multifactorial model, for example, a late onset would indicate a smaller genetic and greater environmental component. A correlation has been found between positive family history of affective illness and early age of the first episode. The presence or absence of a family history of affective illness has also been found to be distinguished by pharmacology, physiology, symptomatology, and severity. It is therefore recommended, for purposes of treatment, that a family history be gathered on patients with depressive illness.", "contents": "The age factor in depressive illness: some genetic considerations. The age of onset of depressive illness may have an association with the genetic character and clinical course of the disorder. There are several genetic models of depressive disorder that are based on differences in age of onset. According to a multifactorial model, for example, a late onset would indicate a smaller genetic and greater environmental component. A correlation has been found between positive family history of affective illness and early age of the first episode. The presence or absence of a family history of affective illness has also been found to be distinguished by pharmacology, physiology, symptomatology, and severity. It is therefore recommended, for purposes of treatment, that a family history be gathered on patients with depressive illness."} {"id": "PMID:1270765", "title": "Somatic therapies in older depressed patients.", "content": "While psychotherapy is the treatment of choice in neurotic situational depressions of older patients, it is not effective enough in endogenous bipolar or monopolar depression of elderly. These respond better to somatic therapy, mainly pharmacotherapy, or, if necessary, ECT. Experience shows the aged endogenous depressions respond favorably to tricyclic antidepressants as well as to mono-amino oxidase inhibitors, although the dosage may have to be kept lower than with younger patients. ECT, if necessary, is well tolerated and effective in aged patients. However, proper precautions have to be taken before this treatment is commenced. Patients with a history or signs of recent coronary thrombosis or decompensated heart failure should be excluded. Also, the number of treatments should be kept at a minimum. The individual treatments should be spaced farther apart and so-called \"intensive treatment\" avoided. If an endogenous depression lasts for more than 2 years and does not respond to any other kind of treatment, psychosurgery may have to be considered. Experience has shown that long-lasting, deep depressions of the aged can be helped by this method without any important personality change.", "contents": "Somatic therapies in older depressed patients. While psychotherapy is the treatment of choice in neurotic situational depressions of older patients, it is not effective enough in endogenous bipolar or monopolar depression of elderly. These respond better to somatic therapy, mainly pharmacotherapy, or, if necessary, ECT. Experience shows the aged endogenous depressions respond favorably to tricyclic antidepressants as well as to mono-amino oxidase inhibitors, although the dosage may have to be kept lower than with younger patients. ECT, if necessary, is well tolerated and effective in aged patients. However, proper precautions have to be taken before this treatment is commenced. Patients with a history or signs of recent coronary thrombosis or decompensated heart failure should be excluded. Also, the number of treatments should be kept at a minimum. The individual treatments should be spaced farther apart and so-called \"intensive treatment\" avoided. If an endogenous depression lasts for more than 2 years and does not respond to any other kind of treatment, psychosurgery may have to be considered. Experience has shown that long-lasting, deep depressions of the aged can be helped by this method without any important personality change."} {"id": "PMID:1270766", "title": "The therapeutic milieu and the older depressed patient.", "content": "A team screening referrals for admission to a state hospital evaluated 434 consecutive cases. Over 51% had a diagnosis of depression. By treating patients in the community, including brief local hospitalization where indicated, total geriatric admission were reduced by 50% per annum. In the final phase of the program, only 10% of admissions to the state hospital were for a primary diagnosis of depression. Almost half of the evaluations required only examination and recommendations, treatment being undertaken by the referring source or another community agency. A further 22% required but one visit to initiate therapy. 17.6% were admitted to treatment, which included drug and group therapy and also milieu therapy by means of transfer, environmental manipulation, and attitude therapy. Only 11.3% needed to be seen weekly or oftener. The program results in considerable savings by reducing unnecessary hospitalization.", "contents": "The therapeutic milieu and the older depressed patient. A team screening referrals for admission to a state hospital evaluated 434 consecutive cases. Over 51% had a diagnosis of depression. By treating patients in the community, including brief local hospitalization where indicated, total geriatric admission were reduced by 50% per annum. In the final phase of the program, only 10% of admissions to the state hospital were for a primary diagnosis of depression. Almost half of the evaluations required only examination and recommendations, treatment being undertaken by the referring source or another community agency. A further 22% required but one visit to initiate therapy. 17.6% were admitted to treatment, which included drug and group therapy and also milieu therapy by means of transfer, environmental manipulation, and attitude therapy. Only 11.3% needed to be seen weekly or oftener. The program results in considerable savings by reducing unnecessary hospitalization."} {"id": "PMID:1270767", "title": "Age and clinical depression: today's youth in the twenty-first century.", "content": "Clinical depression is on the increase in adolescence and young adulthood. Since World War II, psychiatrists are seeing depressed patients who are younger, less severly ill, and more commonly neurotic than psychotic. These patients are most often seen in outpatient and ambulatory settings rather than inpatient hospital facilities. Several reasons have been postulated for this increase; (1) the baby boom following World War II increased the number of people in this age group and (2) the sheer number of people created stresses with which conventional social institutions cannot cope. A shrinking economy and other forces blocking economic gain counteract rising expectations of all young adults, and a situation is created that gives rise to loss of self-esteem, frustation, and perhaps a rising incidence of depression. However, this is just one factor of many which interact which might cause depression. A serious question is whether the reactive depressions of youth will pave the way for endogenous depression in adulthood and old age. Research is needed to determine whether youth will be predisposed to further depressive episodes and, if so, will we be entering a new age of melancholy?", "contents": "Age and clinical depression: today's youth in the twenty-first century. Clinical depression is on the increase in adolescence and young adulthood. Since World War II, psychiatrists are seeing depressed patients who are younger, less severly ill, and more commonly neurotic than psychotic. These patients are most often seen in outpatient and ambulatory settings rather than inpatient hospital facilities. Several reasons have been postulated for this increase; (1) the baby boom following World War II increased the number of people in this age group and (2) the sheer number of people created stresses with which conventional social institutions cannot cope. A shrinking economy and other forces blocking economic gain counteract rising expectations of all young adults, and a situation is created that gives rise to loss of self-esteem, frustation, and perhaps a rising incidence of depression. However, this is just one factor of many which interact which might cause depression. A serious question is whether the reactive depressions of youth will pave the way for endogenous depression in adulthood and old age. Research is needed to determine whether youth will be predisposed to further depressive episodes and, if so, will we be entering a new age of melancholy?"} {"id": "PMID:1270768", "title": "Aging and depression: some unanswered questions.", "content": "The subject of aging and depression leaves many unanswered questions, and the lack of precise and universally accepted definitions (not to mention an inadequate nosology) further complicates the issue. Little is known regarding the differentiation of depressive illness from a melancholic response to the stressful aging process, and equally little regarding the natural history of depressions with onset in the teens, 20s, or 30s. Studies are focusing on biochemical and physiological aspects of depression, but at present biochemists suffer from the uncertainties of the clinicians, and the clinicians and geneticists from the limitations of the biochemists. However, despite our uncertainties about the condition, several effective forms of therapy have been developed, ranging from a focus on the therapeutic milieu to the use of pharmacologic antidepressants (particularly lithium). Ultimately, the question remains: Why are not all elderly persons suffering from depression? The answer may lie in the interaction of environment, life stresses, and the internal adaptive capacities of the individual.", "contents": "Aging and depression: some unanswered questions. The subject of aging and depression leaves many unanswered questions, and the lack of precise and universally accepted definitions (not to mention an inadequate nosology) further complicates the issue. Little is known regarding the differentiation of depressive illness from a melancholic response to the stressful aging process, and equally little regarding the natural history of depressions with onset in the teens, 20s, or 30s. Studies are focusing on biochemical and physiological aspects of depression, but at present biochemists suffer from the uncertainties of the clinicians, and the clinicians and geneticists from the limitations of the biochemists. However, despite our uncertainties about the condition, several effective forms of therapy have been developed, ranging from a focus on the therapeutic milieu to the use of pharmacologic antidepressants (particularly lithium). Ultimately, the question remains: Why are not all elderly persons suffering from depression? The answer may lie in the interaction of environment, life stresses, and the internal adaptive capacities of the individual."} {"id": "PMID:1270769", "title": "Cognitive strategy training and intellectual performance in the elderly.", "content": "Reduced intellectual performance in the elderly was conceptualized as an experientail deficit than can be reversed by training relevant component skills. Sixty female elderly subjects (ages 63 to 95) participated in three phases of the experiment: Training, Immediate Posttest, and Delayed Posttest. Training was geared at strengthening covert self-monitoring strategies in complex reasoning problems, and training effects were evaluated both on the training and a transfer task. Results showed raised performance in the training conditions, transfer effects, and maintenance of training and transfer effects over 2 weeks. Implications for theories of adult intelligence are discussed.", "contents": "Cognitive strategy training and intellectual performance in the elderly. Reduced intellectual performance in the elderly was conceptualized as an experientail deficit than can be reversed by training relevant component skills. Sixty female elderly subjects (ages 63 to 95) participated in three phases of the experiment: Training, Immediate Posttest, and Delayed Posttest. Training was geared at strengthening covert self-monitoring strategies in complex reasoning problems, and training effects were evaluated both on the training and a transfer task. Results showed raised performance in the training conditions, transfer effects, and maintenance of training and transfer effects over 2 weeks. Implications for theories of adult intelligence are discussed."} {"id": "PMID:1270770", "title": "Behavioral observations of mentally impaired aged: those who decline and those who do not.", "content": "Behavioral observations were conducted on aged mentally impaired females in an institutional environment on a weekly basis for a 2-year period. An eight-category taxonomy was used to rate the complexity level of the subjects' behaviors. Although the average weekly performance showed significant linear decline over the 2 years, half the subjects remained stable in the level of their behavioral functioning. In comparison to subjects exhibiting declines in level of functioning, the stable subjects evidenced less serious medical conditions, had better comprehension of their situations, were more socially reactive, manifested fewer neurotic conditions, and had greater control over impulses and aggression at the beginning of the project.", "contents": "Behavioral observations of mentally impaired aged: those who decline and those who do not. Behavioral observations were conducted on aged mentally impaired females in an institutional environment on a weekly basis for a 2-year period. An eight-category taxonomy was used to rate the complexity level of the subjects' behaviors. Although the average weekly performance showed significant linear decline over the 2 years, half the subjects remained stable in the level of their behavioral functioning. In comparison to subjects exhibiting declines in level of functioning, the stable subjects evidenced less serious medical conditions, had better comprehension of their situations, were more socially reactive, manifested fewer neurotic conditions, and had greater control over impulses and aggression at the beginning of the project."} {"id": "PMID:1270771", "title": "Variables associated with the winter camping location of elderly recreational vehical owners in southwestern Arizona.", "content": "During the winter of 1973-1974, 580 elderly recreational vehicle campers were interviewed in six private trailer parks and four public camping areas in southwestern Arizona and Southern California. The ten sites represented four different types of camping environment: (1) highly developed, relatively expensive urban private trailer parks, (2) moderately developed, relatively inexpensive, rural private trailer parks, (3) authorized, developed, free federal campgrounds, and (4) unauthorized, undeveloped, free public land camping areas. Analysis of variance was utilized to identify those respondent characteristics most strongly associated with the type of site selected for winter residence. The most important of these variables were per person annual income, woman's age, man's education, woman's total preretirement adult camping experience, value of mobile quarters and tow vehicle, and percentage of the year lived in a recreational vehicle. Several financial indicators and certain noneconomic characteristics of females were strongly associated with winter camping location.", "contents": "Variables associated with the winter camping location of elderly recreational vehical owners in southwestern Arizona. During the winter of 1973-1974, 580 elderly recreational vehicle campers were interviewed in six private trailer parks and four public camping areas in southwestern Arizona and Southern California. The ten sites represented four different types of camping environment: (1) highly developed, relatively expensive urban private trailer parks, (2) moderately developed, relatively inexpensive, rural private trailer parks, (3) authorized, developed, free federal campgrounds, and (4) unauthorized, undeveloped, free public land camping areas. Analysis of variance was utilized to identify those respondent characteristics most strongly associated with the type of site selected for winter residence. The most important of these variables were per person annual income, woman's age, man's education, woman's total preretirement adult camping experience, value of mobile quarters and tow vehicle, and percentage of the year lived in a recreational vehicle. Several financial indicators and certain noneconomic characteristics of females were strongly associated with winter camping location."} {"id": "PMID:1270772", "title": "Mortality rates among relocated extended-care patients.", "content": "Eighty-one male extended-care patients relocated due to planned demolition of the building in which their ward was located were followed for 21 mo. from the date of transfer. No increase in mortality rate was detected during the first 3 mo. post-relocation, an interval usually associated with high mortality in elderly persons involuntarily relocated. During the first year after relocation, the death rate was 33.33%, compared to an average annual death rate of 41.20% during the 5 years preceding the move. At 21 mo., half the relocated population were alive. These data contrast with previous studies, most of which show increased mortality after relocation, and lead us to concur with those who suggest that the degree of environmental change involved may be a key factor in explaining variance in relocation effects.", "contents": "Mortality rates among relocated extended-care patients. Eighty-one male extended-care patients relocated due to planned demolition of the building in which their ward was located were followed for 21 mo. from the date of transfer. No increase in mortality rate was detected during the first 3 mo. post-relocation, an interval usually associated with high mortality in elderly persons involuntarily relocated. During the first year after relocation, the death rate was 33.33%, compared to an average annual death rate of 41.20% during the 5 years preceding the move. At 21 mo., half the relocated population were alive. These data contrast with previous studies, most of which show increased mortality after relocation, and lead us to concur with those who suggest that the degree of environmental change involved may be a key factor in explaining variance in relocation effects."} {"id": "PMID:1270773", "title": "A mathematical model of aging processes. IV. A multivariate analysis of blood pressure in a Montreal and a Utah population.", "content": "Two populations, one Montreal- and one Utah-based, were studied with respect to heart disease risk factors on a cross-sectional basis. The Utah population afforded consistently lower mean blood pressures than the Montreal population, although there was not evidence that the Utah population was less obese, or had a lower pulse rate. Also, in the Utah population, it was found that the proportion of persons with a family history of heart disease did not differ significantly in the hyper- and normo-tensive groups. Fourteen parameters were investigated in the Montreal population, and the analyses indicated that, when other variables are controlled, age, pulse rate, some measure of serum lipid levels, and a family history of heart disease generally assist in the discrimination between the hyper- and normo-tensive groups, but the obesity measurement did not. In that sense, obesity, on its own, may not be considered a risk factor for hypertension.", "contents": "A mathematical model of aging processes. IV. A multivariate analysis of blood pressure in a Montreal and a Utah population. Two populations, one Montreal- and one Utah-based, were studied with respect to heart disease risk factors on a cross-sectional basis. The Utah population afforded consistently lower mean blood pressures than the Montreal population, although there was not evidence that the Utah population was less obese, or had a lower pulse rate. Also, in the Utah population, it was found that the proportion of persons with a family history of heart disease did not differ significantly in the hyper- and normo-tensive groups. Fourteen parameters were investigated in the Montreal population, and the analyses indicated that, when other variables are controlled, age, pulse rate, some measure of serum lipid levels, and a family history of heart disease generally assist in the discrimination between the hyper- and normo-tensive groups, but the obesity measurement did not. In that sense, obesity, on its own, may not be considered a risk factor for hypertension."} {"id": "PMID:1270774", "title": "Superoxide dismutase in the rat and mouse as a function of age and longevity.", "content": "Superoxide dismutase was assayed in extracts of a variety of tissues in relatively short-lived (A/J) and long-lived (LP/J) male mice. At 9 mo of age the brains and lungs of LP/J mice contained more of this activity than did those of A/J mice. No significant differences were seen in the other tissues investigated. It was also found that specific activities of total superoxide dismutase in extracts of the brain and liver of male CD Sprague-Dawley rats did not diminish during aging; however, the cyanide-insensitive superoxide dismutase, which reflects the mitochondrially localized enzyme and which constitute only a fraction of total activity, did diminish somewhat with age in liver, but not in brain.", "contents": "Superoxide dismutase in the rat and mouse as a function of age and longevity. Superoxide dismutase was assayed in extracts of a variety of tissues in relatively short-lived (A/J) and long-lived (LP/J) male mice. At 9 mo of age the brains and lungs of LP/J mice contained more of this activity than did those of A/J mice. No significant differences were seen in the other tissues investigated. It was also found that specific activities of total superoxide dismutase in extracts of the brain and liver of male CD Sprague-Dawley rats did not diminish during aging; however, the cyanide-insensitive superoxide dismutase, which reflects the mitochondrially localized enzyme and which constitute only a fraction of total activity, did diminish somewhat with age in liver, but not in brain."} {"id": "PMID:1270775", "title": "The effects of improved oral hygiene on taste perception and nutrition of the elderly.", "content": "An experimental group of 12 elderly institutionalized subjects received professional oral hygiene therapy three times weekly for 5 weeks while a control group of 11 received only placebo treatment. The experimental group responded with significantly improved ability to detect sweet and salty tastes but not sour or bitter tastes. No change in taste perception was observed in the controls. Initially, nutrient intake of both groups was suboptimal, especially for folacin. After the treatment period, the intake of calories, hematocrits, hemoglobins, and plasma ascorbic acid concentrations of both groups were satisfactory; plasma proteins were slightly low; plasma folates were at deficiency levels. No change in these blood measurements occurred in either group. It is concluded that improved oral hygiene can enhance taste acuity but that taste perception is only one factor determining nutrient intake.", "contents": "The effects of improved oral hygiene on taste perception and nutrition of the elderly. An experimental group of 12 elderly institutionalized subjects received professional oral hygiene therapy three times weekly for 5 weeks while a control group of 11 received only placebo treatment. The experimental group responded with significantly improved ability to detect sweet and salty tastes but not sour or bitter tastes. No change in taste perception was observed in the controls. Initially, nutrient intake of both groups was suboptimal, especially for folacin. After the treatment period, the intake of calories, hematocrits, hemoglobins, and plasma ascorbic acid concentrations of both groups were satisfactory; plasma proteins were slightly low; plasma folates were at deficiency levels. No change in these blood measurements occurred in either group. It is concluded that improved oral hygiene can enhance taste acuity but that taste perception is only one factor determining nutrient intake."} {"id": "PMID:1270776", "title": "Verbal-pictorial recoding in the elderly.", "content": "Older individuals have been reported to use imagery mediation less often than the young in remembering verbal material. To determine whether this is due to a decrease with age in the speed with which verbal stimuli are recoded into pictorial representations, the reaction time of 12 old (63-78) and 12 young (17-25) subjects for matching verbal description to geometric shapes was measured. While the elderly were generally slower, they were identical to the young in being faster at determining whether or not two simultaneously presented shapes were the same than they were a printed description of a shape and a shape. Also, in both age groups, when 1 or more sec elapsed between the presentation of the description and that of the shape, matching times were as quick as when both stimuli were shapes, suggesting that, for the old as well as the young, 1 sec was sufficient time to recode the description into a pictorial form.", "contents": "Verbal-pictorial recoding in the elderly. Older individuals have been reported to use imagery mediation less often than the young in remembering verbal material. To determine whether this is due to a decrease with age in the speed with which verbal stimuli are recoded into pictorial representations, the reaction time of 12 old (63-78) and 12 young (17-25) subjects for matching verbal description to geometric shapes was measured. While the elderly were generally slower, they were identical to the young in being faster at determining whether or not two simultaneously presented shapes were the same than they were a printed description of a shape and a shape. Also, in both age groups, when 1 or more sec elapsed between the presentation of the description and that of the shape, matching times were as quick as when both stimuli were shapes, suggesting that, for the old as well as the young, 1 sec was sufficient time to recode the description into a pictorial form."} {"id": "PMID:1270777", "title": "The effect of practice on age differences in central perceptual processing.", "content": "The effects of practice on performance in a dichoptic masking paradigm was assessed across two age groups (mean age - 66.5 and 18.8 years). For both age groups practice resulted in a reliable reduction in the time separation between the onset of the target stimulus and the onset of the masking stimulus required to escape masking. The magnitude of reduction was equivalent in both age groups, indicating that the amount of practice in this study does not ameliorate previously demonstrated age differences in speed of central perceptual processing. On the other hand, the equivalent improvement in both age groups suggests no age-related decrement in the adaptability of central perceptual processes.", "contents": "The effect of practice on age differences in central perceptual processing. The effects of practice on performance in a dichoptic masking paradigm was assessed across two age groups (mean age - 66.5 and 18.8 years). For both age groups practice resulted in a reliable reduction in the time separation between the onset of the target stimulus and the onset of the masking stimulus required to escape masking. The magnitude of reduction was equivalent in both age groups, indicating that the amount of practice in this study does not ameliorate previously demonstrated age differences in speed of central perceptual processing. On the other hand, the equivalent improvement in both age groups suggests no age-related decrement in the adaptability of central perceptual processes."} {"id": "PMID:1270778", "title": "Satisfaction with life among persons sixty-five years and older. A causal model.", "content": "A fully recursive path model heuristically depicting a causative chain between financial situation, health satisfaction, satisfaction with standard of living, satisfaction with family life, and satisfaction with life as a whole was examined. The model was evaluated via path analysis, with parallel analyses conducted for each sex. The data used in this analysis were collected from a national probability sample of persons aged 18 and over living in noninstitutional dwelling units. This present study includes only those persons 65 years and older (N = 301). The model was shown to be an effective predictor of satisfaction with life for each sex. Satisfaction with family was found to make the greatest single impact on life satisfaction. Moreover, the model was determined to be generally consistent throughout.", "contents": "Satisfaction with life among persons sixty-five years and older. A causal model. A fully recursive path model heuristically depicting a causative chain between financial situation, health satisfaction, satisfaction with standard of living, satisfaction with family life, and satisfaction with life as a whole was examined. The model was evaluated via path analysis, with parallel analyses conducted for each sex. The data used in this analysis were collected from a national probability sample of persons aged 18 and over living in noninstitutional dwelling units. This present study includes only those persons 65 years and older (N = 301). The model was shown to be an effective predictor of satisfaction with life for each sex. Satisfaction with family was found to make the greatest single impact on life satisfaction. Moreover, the model was determined to be generally consistent throughout."} {"id": "PMID:1270779", "title": "Retired academics and research activity.", "content": "A limited literature on the retirement of academics suggests that they do not follow the expected pattern of retirement but may be similar to scientists in retirement. Data collected from 207 academics who retired from state and small private colleges and ivy league and large state universities indicate that to varying degrees they continue to engage in professional activities after retirement. Academics who are high on professional visibility appear to be especially likely to continue to engage in research and/or writing. The importance of psychological centrality of pre-retirement work to post-retirement activity is suggested.", "contents": "Retired academics and research activity. A limited literature on the retirement of academics suggests that they do not follow the expected pattern of retirement but may be similar to scientists in retirement. Data collected from 207 academics who retired from state and small private colleges and ivy league and large state universities indicate that to varying degrees they continue to engage in professional activities after retirement. Academics who are high on professional visibility appear to be especially likely to continue to engage in research and/or writing. The importance of psychological centrality of pre-retirement work to post-retirement activity is suggested."} {"id": "PMID:1270780", "title": "Age profiles of membership in sixteen types of voluntary associations.", "content": "Several trends are noted which may lead future cohorts of older persons to belong to voluntary associations to a greater extent than current cohorts. Because the best previously available data which could be used to monitor changing membership levels are not two decades old, this study presents detailed age profiles of membership in 16 types of associations. Based on data from the 1974 and 1975 NORC General Social Surveys of the adult population of the USA (N = 2,974), various patterns of age differences in belonging to associations are identified and discussed for both the total sample and by sex. A rank order of the types of associations to which older persons are most likely to belong in 1974-1975 is compared with a similar rank order based on a 1955 survey. The paper concludes by specifying additional research questions which replicate studies should address.", "contents": "Age profiles of membership in sixteen types of voluntary associations. Several trends are noted which may lead future cohorts of older persons to belong to voluntary associations to a greater extent than current cohorts. Because the best previously available data which could be used to monitor changing membership levels are not two decades old, this study presents detailed age profiles of membership in 16 types of associations. Based on data from the 1974 and 1975 NORC General Social Surveys of the adult population of the USA (N = 2,974), various patterns of age differences in belonging to associations are identified and discussed for both the total sample and by sex. A rank order of the types of associations to which older persons are most likely to belong in 1974-1975 is compared with a similar rank order based on a 1955 survey. The paper concludes by specifying additional research questions which replicate studies should address."} {"id": "PMID:1270793", "title": "A rapid, simple and sensitive method for the demonstration of central catecholamine-containing neurons and axons by glyoxylic acid-induced fluorescence. II. A detailed description of methodology.", "content": "The glyoxylic acid-induced fluorescence method for localization of brain catecholamine neurons has been modified. Fluorescence is developed rapidly in cryostat sections of brains fixed by perfusion with 0.5% depolymerized paraformaldehyde and 2.0% glyoxylic acid. Since neither freeze drying nor vibratome sectioning is required, total processing time can be less than 1 hr. Both perikarya and fine varicose axons of norepinephrine- and dopamine-containing neurons can be seen throughout the neuroaxis. The modified technique retains good cytologic integrity and may provide a useful alternative for methods combining histochemical approaches.", "contents": "A rapid, simple and sensitive method for the demonstration of central catecholamine-containing neurons and axons by glyoxylic acid-induced fluorescence. II. A detailed description of methodology. The glyoxylic acid-induced fluorescence method for localization of brain catecholamine neurons has been modified. Fluorescence is developed rapidly in cryostat sections of brains fixed by perfusion with 0.5% depolymerized paraformaldehyde and 2.0% glyoxylic acid. Since neither freeze drying nor vibratome sectioning is required, total processing time can be less than 1 hr. Both perikarya and fine varicose axons of norepinephrine- and dopamine-containing neurons can be seen throughout the neuroaxis. The modified technique retains good cytologic integrity and may provide a useful alternative for methods combining histochemical approaches."} {"id": "PMID:1270790", "title": "Spontaneous seizures: a new mutation in Syrian golden hamsters.", "content": "Hereditary spontaneous seizures in the Syrian hamsters are described. The seizures occur in 30 to 60-day-old animals from about 2 to 5 hours. The condition is a simple recessive trait, and the gene symbol sz is proposed.", "contents": "Spontaneous seizures: a new mutation in Syrian golden hamsters. Hereditary spontaneous seizures in the Syrian hamsters are described. The seizures occur in 30 to 60-day-old animals from about 2 to 5 hours. The condition is a simple recessive trait, and the gene symbol sz is proposed."} {"id": "PMID:1270794", "title": "The distribution of 14c from [U-14c]glucose in mice using whole-body autoradiography.", "content": "Tissue distribution of radioactive carbon from [U-14C]glucose in the mouse in vivo was studied by whole-body autoradiography. The mice were frozen with Dry-Ice-acetone at 0.5, 1, 5 and 30 min, 1 and 24 hr and 1 and 3 weeks after intraperitoneal injection of [U-14C]glucose. Whole-sagittal sections of the frozen mouse, obtained by using a microtome in a cryostat, were dried in a cryostat and autoradiographed. The resulting dry autoradiographs are called untreated autoradiographs in the present work. The sections were then fixed in cold 6% (w/v) HClO4, dried at room temperature and again autoradiographed. Autoradiographs that have undergone this process are referred to as treated autoradiographs. In both untreated and treated autoradiographs, within 1 min following injection of the labeled glucose, the abdominal cavity had the highest autoradiographic density. At 1 hr, density became highest in Harder's, sublingual and duodenal glands, large intestinal mucosa and tongue, and after 3 weeks, no autoradiographic denisty was present.", "contents": "The distribution of 14c from [U-14c]glucose in mice using whole-body autoradiography. Tissue distribution of radioactive carbon from [U-14C]glucose in the mouse in vivo was studied by whole-body autoradiography. The mice were frozen with Dry-Ice-acetone at 0.5, 1, 5 and 30 min, 1 and 24 hr and 1 and 3 weeks after intraperitoneal injection of [U-14C]glucose. Whole-sagittal sections of the frozen mouse, obtained by using a microtome in a cryostat, were dried in a cryostat and autoradiographed. The resulting dry autoradiographs are called untreated autoradiographs in the present work. The sections were then fixed in cold 6% (w/v) HClO4, dried at room temperature and again autoradiographed. Autoradiographs that have undergone this process are referred to as treated autoradiographs. In both untreated and treated autoradiographs, within 1 min following injection of the labeled glucose, the abdominal cavity had the highest autoradiographic density. At 1 hr, density became highest in Harder's, sublingual and duodenal glands, large intestinal mucosa and tongue, and after 3 weeks, no autoradiographic denisty was present."} {"id": "PMID:1270791", "title": "Palp-antenna, a homeotic mutant in Aedes aegypti.", "content": "Palp-antenna is a homeotic mutant of Aedes aegypti that modifies the apex of the maxillary palps of both sexes into a variable number of antenna-like segments. The fine structure of the antenna, including sexual dimorphism, is apparent in the mutant palps. Palp-antenna is a sex-linked recessive. a linkage distance of 27.9 +/- 0.45 crossover units from sex is estimated from F2 and backcross data. Penetrance is complete; expressively is variable. The fitness of the mutant compares favorably with that of the wild type. The mapping of the ppa locus lengthens the known chromosome 1 linkage map of Aedes aegypti.", "contents": "Palp-antenna, a homeotic mutant in Aedes aegypti. Palp-antenna is a homeotic mutant of Aedes aegypti that modifies the apex of the maxillary palps of both sexes into a variable number of antenna-like segments. The fine structure of the antenna, including sexual dimorphism, is apparent in the mutant palps. Palp-antenna is a sex-linked recessive. a linkage distance of 27.9 +/- 0.45 crossover units from sex is estimated from F2 and backcross data. Penetrance is complete; expressively is variable. The fitness of the mutant compares favorably with that of the wild type. The mapping of the ppa locus lengthens the known chromosome 1 linkage map of Aedes aegypti."} {"id": "PMID:1270792", "title": "Inherited ateliotic dwarfism in mice. Characteristics of the mutation, little, on chromosome 6.", "content": "A new autosomal recessive mutation in the mouse, little (lit), has been shown to be located on Chromosome 6. The mutation in the homozygous state causes ateliotic dwarfism that is first detected at 15 days of age by decreased body weight. Long bone lengths are significantly reduced. Skull width, however, is not affected. Female little mice are fully fertile; they may lose their first litters. Although most of the little males sire one or two litters, they rarely sire a third litter. Analysis of pituitary extracts electrophoresed on acrylamide gels reveal a significant reduction of the two anterior pituitary hormones, GH and PRL, in both male and female little mice. Because the little mouse shares a number of similarities with the human ateliotic dwarfism, isolated growth hormones deficiency type I, it may be a useful animal model for this inherited human growth disorder.", "contents": "Inherited ateliotic dwarfism in mice. Characteristics of the mutation, little, on chromosome 6. A new autosomal recessive mutation in the mouse, little (lit), has been shown to be located on Chromosome 6. The mutation in the homozygous state causes ateliotic dwarfism that is first detected at 15 days of age by decreased body weight. Long bone lengths are significantly reduced. Skull width, however, is not affected. Female little mice are fully fertile; they may lose their first litters. Although most of the little males sire one or two litters, they rarely sire a third litter. Analysis of pituitary extracts electrophoresed on acrylamide gels reveal a significant reduction of the two anterior pituitary hormones, GH and PRL, in both male and female little mice. Because the little mouse shares a number of similarities with the human ateliotic dwarfism, isolated growth hormones deficiency type I, it may be a useful animal model for this inherited human growth disorder."} {"id": "PMID:1270796", "title": "Changes in C3 metabolism during protozoan infection (Babesia rodhaini) in rats.", "content": "Metabolism of the third component of complement (C3) and IgG was measured in rats before and during infection with the hemosporidium agent Babesia rodhaina. In the course of infection, hypocomplementemia and immune complex nephritis developed. During babesial infection, in most animals the half-life of C3 fell sharply, as did serum levels of C3; the catabolic rate for C3 sharply increased, whereas the synthetic rate sharply decreased. In contrast, the catabolic rate for IgG remained unchanged. The alteration in the metabolism of C3 in the face of nonparallel changes in IgG metabolism suggests that abnormal glomerular filtration and increased vasopermeability cannot explain the findings. Babesial infection in the rat provides a useful model for the study of acquired C3 metabolic defects that have been observed in humans with immune complex diseases.", "contents": "Changes in C3 metabolism during protozoan infection (Babesia rodhaini) in rats. Metabolism of the third component of complement (C3) and IgG was measured in rats before and during infection with the hemosporidium agent Babesia rodhaina. In the course of infection, hypocomplementemia and immune complex nephritis developed. During babesial infection, in most animals the half-life of C3 fell sharply, as did serum levels of C3; the catabolic rate for C3 sharply increased, whereas the synthetic rate sharply decreased. In contrast, the catabolic rate for IgG remained unchanged. The alteration in the metabolism of C3 in the face of nonparallel changes in IgG metabolism suggests that abnormal glomerular filtration and increased vasopermeability cannot explain the findings. Babesial infection in the rat provides a useful model for the study of acquired C3 metabolic defects that have been observed in humans with immune complex diseases."} {"id": "PMID:1270797", "title": "Release of tumor-associated antigens by murine melanoma cells.", "content": "Synthesis and release of radiolabeled macromolecules and tumor-associated antigens (MAA) by murine B16 melanoma was studied by pulse labeling cells in culture with 3H-leucine. Approximately 36% of newly synthesized macromolecules and 44% of newly synthesized MAA were released in 48 hr. MAA release was slightly, but consistently, more rapid than the average release of other macromolecules. Release of MAA did not result solely from cell death since it was greater than that of 51Cr-labeled molecules and cell viability was over 98%. The rate of release of newly synthesized MAA was not significantly influenced by cell replication. However, synthesis of MAA was much greater during the logarithmic than the stationary phase of cell growth, suggesting a concomitant increase in the amount of MAA available for release. These findings indicate that antigens and other macromolecules can be rapidly released by viable tumor cells.", "contents": "Release of tumor-associated antigens by murine melanoma cells. Synthesis and release of radiolabeled macromolecules and tumor-associated antigens (MAA) by murine B16 melanoma was studied by pulse labeling cells in culture with 3H-leucine. Approximately 36% of newly synthesized macromolecules and 44% of newly synthesized MAA were released in 48 hr. MAA release was slightly, but consistently, more rapid than the average release of other macromolecules. Release of MAA did not result solely from cell death since it was greater than that of 51Cr-labeled molecules and cell viability was over 98%. The rate of release of newly synthesized MAA was not significantly influenced by cell replication. However, synthesis of MAA was much greater during the logarithmic than the stationary phase of cell growth, suggesting a concomitant increase in the amount of MAA available for release. These findings indicate that antigens and other macromolecules can be rapidly released by viable tumor cells."} {"id": "PMID:1270798", "title": "Pathogenetic mechanisms in immune polioencephalomyelitis: quantitative evaluation of protective and pathogenic effects of lymphoid cells.", "content": "Terminal dilution, adoptive cell transfer techniques were developed to quantify the protective effect of lymphoid cells in the pathogenesis of immune polioencephalomyelitis (IPE). The pathogenic effects of lymphoid cell populations were quantified by deleting the step of antigenic challenge. Regression curves were computer analyzed and PD50 values were compared. Immune spleen cells (ISC) from 4- to 6-week-old donors were more protective (PD50 = 4.9 +/- 1.3) than ISC from 12-month-old animals (PD50 greater than 7.0). The slopes of the regression curves also differed markedly (young mice, -0.24; old mice, -0.09). ISC were less protective in 12-month-indicator mice than in 5-month-old recipients (PD50 values of 5.2 +/- 0.8 and 3.7 +/- 0.8, respectively). When adoptive cell transfer tests were used to quantify the pathogenetic effects of donor cells it was found that ISC were pathogenetic at doses of 10(5) or less, but protective at higher doses. IPEC were pathogenetic at all test doses. When ISC were x-irradiated or sonicated the were only pathogenetic. Normal spleen or peritoneal exudate cells were neither protective nor pathogenetic. A model was developed in which mice were either thymectomized at birth (Tx), or Tx at birth and x-irradiated (500 R) 8 weeks later (Tx-XR). Sham Tx or Tx-XR mice served as controls. All of the mice were challenged with antigen (10(4) x-irradiated Ib cells). Only a portion (8/24) of the Tx mice developed IPE, indicating that resistance was T cell dependent but also involved a significant T cell independent component. The data also indicated that T cells were not pathogenetic effector cells in this model. Tx mice were not reconstituted by ISC (7/18 developed IPE), Tx-XR mice were partially reconstituted (3/12 developed IPE), but sham Tx-XR were fully restored (0/20 had IPE). Normal spleen cells did not reconstitute any of the mice.", "contents": "Pathogenetic mechanisms in immune polioencephalomyelitis: quantitative evaluation of protective and pathogenic effects of lymphoid cells. Terminal dilution, adoptive cell transfer techniques were developed to quantify the protective effect of lymphoid cells in the pathogenesis of immune polioencephalomyelitis (IPE). The pathogenic effects of lymphoid cell populations were quantified by deleting the step of antigenic challenge. Regression curves were computer analyzed and PD50 values were compared. Immune spleen cells (ISC) from 4- to 6-week-old donors were more protective (PD50 = 4.9 +/- 1.3) than ISC from 12-month-old animals (PD50 greater than 7.0). The slopes of the regression curves also differed markedly (young mice, -0.24; old mice, -0.09). ISC were less protective in 12-month-indicator mice than in 5-month-old recipients (PD50 values of 5.2 +/- 0.8 and 3.7 +/- 0.8, respectively). When adoptive cell transfer tests were used to quantify the pathogenetic effects of donor cells it was found that ISC were pathogenetic at doses of 10(5) or less, but protective at higher doses. IPEC were pathogenetic at all test doses. When ISC were x-irradiated or sonicated the were only pathogenetic. Normal spleen or peritoneal exudate cells were neither protective nor pathogenetic. A model was developed in which mice were either thymectomized at birth (Tx), or Tx at birth and x-irradiated (500 R) 8 weeks later (Tx-XR). Sham Tx or Tx-XR mice served as controls. All of the mice were challenged with antigen (10(4) x-irradiated Ib cells). Only a portion (8/24) of the Tx mice developed IPE, indicating that resistance was T cell dependent but also involved a significant T cell independent component. The data also indicated that T cells were not pathogenetic effector cells in this model. Tx mice were not reconstituted by ISC (7/18 developed IPE), Tx-XR mice were partially reconstituted (3/12 developed IPE), but sham Tx-XR were fully restored (0/20 had IPE). Normal spleen cells did not reconstitute any of the mice."} {"id": "PMID:1270799", "title": "Suppressor cells in the spleens of tumor-bearing mice: enrichment by centrifugation on hypaque-ficoll and characterization of the suppressor population.", "content": "Spleen cells from mice bearing methylcholanthrene-induced sarcomas or a mammary adenocarcinoma suppressed the mitogen responses of normal spleen and lymph node cells. Lymph node cells from tumor bearers had no suppressive effects. Centrifugation of spleen cells layered on Hypaque-Ficoll (specific gravity of 1.08) produced a dense fraction which pelleted and a light fraction which was retained at the Hypaque-Ficoll-medium interface. Suppressive activity was not found in either fraction of normal spleen cells. In tumor-bearer spleen cells suppressor activity was greatly enriched in the light fraction. Treatment of the suppressor fraction with anti-theta or anti-Ig serum and complement did not remove suppressor activity. However, the suppressor cells were removed by passage through nylon wool or by carbonyl iron treatment. Also, the population which adhered to plastic Petri dishes contained the suppressor cell activity.", "contents": "Suppressor cells in the spleens of tumor-bearing mice: enrichment by centrifugation on hypaque-ficoll and characterization of the suppressor population. Spleen cells from mice bearing methylcholanthrene-induced sarcomas or a mammary adenocarcinoma suppressed the mitogen responses of normal spleen and lymph node cells. Lymph node cells from tumor bearers had no suppressive effects. Centrifugation of spleen cells layered on Hypaque-Ficoll (specific gravity of 1.08) produced a dense fraction which pelleted and a light fraction which was retained at the Hypaque-Ficoll-medium interface. Suppressive activity was not found in either fraction of normal spleen cells. In tumor-bearer spleen cells suppressor activity was greatly enriched in the light fraction. Treatment of the suppressor fraction with anti-theta or anti-Ig serum and complement did not remove suppressor activity. However, the suppressor cells were removed by passage through nylon wool or by carbonyl iron treatment. Also, the population which adhered to plastic Petri dishes contained the suppressor cell activity."} {"id": "PMID:1270800", "title": "Antibody against the antigen receptor of a plasmacytoma prolongs survival of mice bearing the tumor.", "content": "A transplantable plasmacytoma, TEPC-15 in BALB/c mice, induces a transient antibody response directed against the combining region of the myeloma protein produced by the tumor. Mice immunized with mitomycin-treated tumor cells produce similar antibody but do not develop tumor; mice so immunized survive longer than untreated mice when inoculated with viable TEPC-15 cells. This protection afforded by immunization can be transferred by serum alone; the protective effect of passively given serum is eliminated by absorbing out antibody directed against the myeloma protein.", "contents": "Antibody against the antigen receptor of a plasmacytoma prolongs survival of mice bearing the tumor. A transplantable plasmacytoma, TEPC-15 in BALB/c mice, induces a transient antibody response directed against the combining region of the myeloma protein produced by the tumor. Mice immunized with mitomycin-treated tumor cells produce similar antibody but do not develop tumor; mice so immunized survive longer than untreated mice when inoculated with viable TEPC-15 cells. This protection afforded by immunization can be transferred by serum alone; the protective effect of passively given serum is eliminated by absorbing out antibody directed against the myeloma protein."} {"id": "PMID:1270801", "title": "Isolation and partial characterization of SAA-an amyloid-related protein from human serum.", "content": "A 12,000 dalton serum amyloid A protein (SAA) has been isolated by chromatography on Sephadex in 10% formic acid. It is similar immunologically to the previously characterized 8500 dalton tissue amyloid A (AA) protein. The results of amino acid analyses, peptide maps, and the identity of the first 11 residues of the SAA and AA proteins support the idea that AA represents the amino terminal fragment of SAA and is derived from it by proteolysis.", "contents": "Isolation and partial characterization of SAA-an amyloid-related protein from human serum. A 12,000 dalton serum amyloid A protein (SAA) has been isolated by chromatography on Sephadex in 10% formic acid. It is similar immunologically to the previously characterized 8500 dalton tissue amyloid A (AA) protein. The results of amino acid analyses, peptide maps, and the identity of the first 11 residues of the SAA and AA proteins support the idea that AA represents the amino terminal fragment of SAA and is derived from it by proteolysis."} {"id": "PMID:1270802", "title": "The C5b-9 complex: subunit composition of the classical and alternative pathway-generated complex.", "content": "The membrane attack complex of complement (C5b-9) is identical in composition regardless of which pathway of activation was instrumental in its formation. Band V protein was consistently a subunit of the soluble complex. Since band V protein is not required for complement-dependent cytolysis, it probably represents a membrane site equivalent in serum of the nascent C5b-9 complex.", "contents": "The C5b-9 complex: subunit composition of the classical and alternative pathway-generated complex. The membrane attack complex of complement (C5b-9) is identical in composition regardless of which pathway of activation was instrumental in its formation. Band V protein was consistently a subunit of the soluble complex. Since band V protein is not required for complement-dependent cytolysis, it probably represents a membrane site equivalent in serum of the nascent C5b-9 complex."} {"id": "PMID:1270803", "title": "Redistribution of the Fc receptor on human blood monocytes and peritoneal macrophages induced by immunoglobulin G-sensitized erythrocytes.", "content": "The Fc receptor is a plasma membrane component exhibiting an affinity for the C gamma 3 domain of certain subclasses of immunoglobulin G. Using anti-Rho (D)-sensitized red cells (EA) in a slide rosette technique, we have demonstrated a translational mobility and polar redistribution of this receptor on the human blood monocyte and peritoneal macrophage. These cells, isolated from venous blood and malignant ascites and identified histochemically, showed a time- and temperature-dependent receptor capping defined by binding six or more EA confined to the cell half-perimeter. Caps formed in serum were mainly extreme caps in which bound EA appeared as a morula contiguous with the adherent cell. At 21 degrees C and 37 degrees C in serum 80% live rosettes formed caps; virtually none formed at 4 degrees C and about 25% were seen in PBS at 21 degrees C. Similarly, 10% extreme caps in PBS and 60 and 70% in serum were seen at room temperature and 37 degrees C, respectively, suggesting a serum factor(s) was important in promoting live rosette capping. Capping was reversibly inhibited by sodium azide although inhibition was incomplete even at 0.1 M, a concentration 10-fold higher than that giving complete inhibition of lymphocyte antigen-receptor capping. Azide also induced reversion of capped rosettes to diffuse, noncapped rosettes, and to levels comparable to those seen in inhibition studies. Re-exposure to EA after rosette capping failed to increase either the proportion of cells forming rosettes or the fullness of such rosettes indicating a critical number of receptors had been capped. Live rosettes induced a spherocytosis in bound EA irrespective of capping status; such changes appeared early in PBS where capping was minimal. Dead cells bore EA as normal biconcave discs. Some rosetting EA were ultimately hemolyzed upon prolonged incubation, and erythrophagocytosis was seen in about 15% of capped rosettes at 37 degrees C.", "contents": "Redistribution of the Fc receptor on human blood monocytes and peritoneal macrophages induced by immunoglobulin G-sensitized erythrocytes. The Fc receptor is a plasma membrane component exhibiting an affinity for the C gamma 3 domain of certain subclasses of immunoglobulin G. Using anti-Rho (D)-sensitized red cells (EA) in a slide rosette technique, we have demonstrated a translational mobility and polar redistribution of this receptor on the human blood monocyte and peritoneal macrophage. These cells, isolated from venous blood and malignant ascites and identified histochemically, showed a time- and temperature-dependent receptor capping defined by binding six or more EA confined to the cell half-perimeter. Caps formed in serum were mainly extreme caps in which bound EA appeared as a morula contiguous with the adherent cell. At 21 degrees C and 37 degrees C in serum 80% live rosettes formed caps; virtually none formed at 4 degrees C and about 25% were seen in PBS at 21 degrees C. Similarly, 10% extreme caps in PBS and 60 and 70% in serum were seen at room temperature and 37 degrees C, respectively, suggesting a serum factor(s) was important in promoting live rosette capping. Capping was reversibly inhibited by sodium azide although inhibition was incomplete even at 0.1 M, a concentration 10-fold higher than that giving complete inhibition of lymphocyte antigen-receptor capping. Azide also induced reversion of capped rosettes to diffuse, noncapped rosettes, and to levels comparable to those seen in inhibition studies. Re-exposure to EA after rosette capping failed to increase either the proportion of cells forming rosettes or the fullness of such rosettes indicating a critical number of receptors had been capped. Live rosettes induced a spherocytosis in bound EA irrespective of capping status; such changes appeared early in PBS where capping was minimal. Dead cells bore EA as normal biconcave discs. Some rosetting EA were ultimately hemolyzed upon prolonged incubation, and erythrophagocytosis was seen in about 15% of capped rosettes at 37 degrees C."} {"id": "PMID:1270804", "title": "Motheater: an immunodeficient mouse with markedly less ability to survive that the nude mouse in a germfree environment.", "content": "The motheaten mouse is an immunodeficient mutant which has been found to have elevated immunoglobulin levels, to exhibit autoimmunity, and early death. Since survival is not improved by a germfree environment, it appears that some mechanism other than infection results in its early demise.", "contents": "Motheater: an immunodeficient mouse with markedly less ability to survive that the nude mouse in a germfree environment. The motheaten mouse is an immunodeficient mutant which has been found to have elevated immunoglobulin levels, to exhibit autoimmunity, and early death. Since survival is not improved by a germfree environment, it appears that some mechanism other than infection results in its early demise."} {"id": "PMID:1270805", "title": "Radiolabeling of immunoglobulin without loss of antibody activity--use of 14C-phenylisothiocyanate with human cytotoxic antibody.", "content": "Radioiodination of immunoglobulins, particularly human cytotoxic IgG, induced a marked loss of antibody activity. Phenylisothiocyanate (PITC) readily reacts with alpha-amino groups and the epsilon-amino groups of lysines to form phenylthiocarbamyl derivatives. Since PITC is commercially available with 14C, 3H, and 35S substitutions, it provided an alternative means for labeling immunoglobulin which preserved antibody activity. There were approximately 80 PITC binding sites per IgG molecule, and 14C-PITC was bound with an efficiency in excess of 80%. With as many as 40 PITC molecules bound per IgG molecule, full cytotoxic activity was retained by both anti-HLA isoantisera and human anti-melanoma autoantisera. Even with 70 to 80 molecules of PITC bound per IgG molecule, over 80% of the antibody activity remained. Radiolabeling of antibody with 3H, 14C, or 35S-substituted PITC will greatly facilitate studies of antibody binding, particularly to cell surface antigens.", "contents": "Radiolabeling of immunoglobulin without loss of antibody activity--use of 14C-phenylisothiocyanate with human cytotoxic antibody. Radioiodination of immunoglobulins, particularly human cytotoxic IgG, induced a marked loss of antibody activity. Phenylisothiocyanate (PITC) readily reacts with alpha-amino groups and the epsilon-amino groups of lysines to form phenylthiocarbamyl derivatives. Since PITC is commercially available with 14C, 3H, and 35S substitutions, it provided an alternative means for labeling immunoglobulin which preserved antibody activity. There were approximately 80 PITC binding sites per IgG molecule, and 14C-PITC was bound with an efficiency in excess of 80%. With as many as 40 PITC molecules bound per IgG molecule, full cytotoxic activity was retained by both anti-HLA isoantisera and human anti-melanoma autoantisera. Even with 70 to 80 molecules of PITC bound per IgG molecule, over 80% of the antibody activity remained. Radiolabeling of antibody with 3H, 14C, or 35S-substituted PITC will greatly facilitate studies of antibody binding, particularly to cell surface antigens."} {"id": "PMID:1270806", "title": "Receptors for immune complexes on cells within a non-lymphoid murine tumor.", "content": "In this paper we present evidence that antibodies unrelated to the tumor cell can comprise part of the in vivo Ig surface coat of cells derived from the non-lymphoid murine tumor, TA3/St. This was shown by incubating TA3 cells originating from other OA or BSA preimmunized mice with radioiodinated 125I-OA and 131I BSA. Radioiodine-labeled 125I-OA specifically fixed to cells derived from TA3/St tumors originating from OA-preimmunized mice. On the other hand 131I-BSA was specifically fixed by cell populations from BSA-preimmunized mice. Incubation of these cells in vitro at 37 degrees C abolished the specific binding and antibody could subsequently be detected in the tissue culture medium. Radioiodine labeled purified soluble antibody-antigen complexes could also be bound to cells derived from freshly harvested TA3/St tumors but not to their in vitro propagated counterparts. Removal of phagocytic or adherent cells from these cell populations decreased the binding of the complexed antibody on freshly harvested TA3/St populations, but did not eliminate it. Inhibition of complexed antibody binding was obtained when TA3/St cells (an H-2a tumor) were pre-incubated with anti-H2a antiserum. Propagation of the tumor in an F1 hybrid (A X C57BL) in which host cells could be distinguished from tumor cells by using an anti H-2b antiserum showed that binding of the immune complex was mostly limited to host cells infiltrating into the tumor population.", "contents": "Receptors for immune complexes on cells within a non-lymphoid murine tumor. In this paper we present evidence that antibodies unrelated to the tumor cell can comprise part of the in vivo Ig surface coat of cells derived from the non-lymphoid murine tumor, TA3/St. This was shown by incubating TA3 cells originating from other OA or BSA preimmunized mice with radioiodinated 125I-OA and 131I BSA. Radioiodine-labeled 125I-OA specifically fixed to cells derived from TA3/St tumors originating from OA-preimmunized mice. On the other hand 131I-BSA was specifically fixed by cell populations from BSA-preimmunized mice. Incubation of these cells in vitro at 37 degrees C abolished the specific binding and antibody could subsequently be detected in the tissue culture medium. Radioiodine labeled purified soluble antibody-antigen complexes could also be bound to cells derived from freshly harvested TA3/St tumors but not to their in vitro propagated counterparts. Removal of phagocytic or adherent cells from these cell populations decreased the binding of the complexed antibody on freshly harvested TA3/St populations, but did not eliminate it. Inhibition of complexed antibody binding was obtained when TA3/St cells (an H-2a tumor) were pre-incubated with anti-H2a antiserum. Propagation of the tumor in an F1 hybrid (A X C57BL) in which host cells could be distinguished from tumor cells by using an anti H-2b antiserum showed that binding of the immune complex was mostly limited to host cells infiltrating into the tumor population."} {"id": "PMID:1270807", "title": "The formation of septate-like junctional complexes between lymphoid cells in vitro.", "content": "During the initial 48 hr of incubation in immunized Mishell-Dutton spleen cell cultures, most lymphocytes exist as single cells or an occasional pair of cells (doublets). Ultrastructural examination of the area between those cells forming doublets revealed a septate-like junctional complex occurring over large portions of the plasmalemma. This junctional zone persisted in areas where extensive cytoplasmic interdigitation among cell processes was evident. Approximately 1% of the lymphocytes isolated from the top fraction of a discontinuous fetal calf serum gradient were involved in formation of doublets. The majority of these doublets showed evidence of junctional interaction. Moreover, this septate-like zone of adhesion was seen using several different fixatives and stains and remained intact after osmotic cell disruption. The junction was not demonstrable by using freeze-fracture techniques and therefore must be limited to interactions within the surface of the cells.", "contents": "The formation of septate-like junctional complexes between lymphoid cells in vitro. During the initial 48 hr of incubation in immunized Mishell-Dutton spleen cell cultures, most lymphocytes exist as single cells or an occasional pair of cells (doublets). Ultrastructural examination of the area between those cells forming doublets revealed a septate-like junctional complex occurring over large portions of the plasmalemma. This junctional zone persisted in areas where extensive cytoplasmic interdigitation among cell processes was evident. Approximately 1% of the lymphocytes isolated from the top fraction of a discontinuous fetal calf serum gradient were involved in formation of doublets. The majority of these doublets showed evidence of junctional interaction. Moreover, this septate-like zone of adhesion was seen using several different fixatives and stains and remained intact after osmotic cell disruption. The junction was not demonstrable by using freeze-fracture techniques and therefore must be limited to interactions within the surface of the cells."} {"id": "PMID:1270808", "title": "Purification of homogeneous murine immunoglobulins with anti-fructofuranan specificity.", "content": "Homogenous IgAK immunoglobulins ABPC-47 new, EPC-109, UPC-61 (anti-2,1 fructofuranan specificity) and homogeneous IgAK ABPC-48 and IgGK UPC-10 (anti-2,6 fructofuranan specificity) were purified by affinity chromatography by using inulin- and grass levan-Sepharose columns, respectively.", "contents": "Purification of homogeneous murine immunoglobulins with anti-fructofuranan specificity. Homogenous IgAK immunoglobulins ABPC-47 new, EPC-109, UPC-61 (anti-2,1 fructofuranan specificity) and homogeneous IgAK ABPC-48 and IgGK UPC-10 (anti-2,6 fructofuranan specificity) were purified by affinity chromatography by using inulin- and grass levan-Sepharose columns, respectively."} {"id": "PMID:1270810", "title": "Mononuclear cells migration inhibition and delayed hypersensitivity in man.", "content": "The migration inhibition by soluble PPD of peripheral blood mononuclear cells showed a much better reflection of delayed hypersentitivity to tuberculin in man than the migration inhibition of buffy coat cells. The migration index (MI) with mononuclear cells in a group of tuberculin positive subjects was 0.51 +/- 0.14 (mean +/- S.D.) (n = 20) and that of a group of tuberculin negative subjects was 0.89 +/- 0.11 (n = 14) (P less than 0.001). Using buffy coat cells the MI was 0.65 +/- 0.26 (n = 19) for a group of tuberculin positive subjects and 0.76 +/- 0.24 (n = 10) for the group of tuberculin negative subjects. They were not significantly different (P greater than 0.05). The mononuclear cells migration inhibition was also quite reproducible from day to day.", "contents": "Mononuclear cells migration inhibition and delayed hypersensitivity in man. The migration inhibition by soluble PPD of peripheral blood mononuclear cells showed a much better reflection of delayed hypersentitivity to tuberculin in man than the migration inhibition of buffy coat cells. The migration index (MI) with mononuclear cells in a group of tuberculin positive subjects was 0.51 +/- 0.14 (mean +/- S.D.) (n = 20) and that of a group of tuberculin negative subjects was 0.89 +/- 0.11 (n = 14) (P less than 0.001). Using buffy coat cells the MI was 0.65 +/- 0.26 (n = 19) for a group of tuberculin positive subjects and 0.76 +/- 0.24 (n = 10) for the group of tuberculin negative subjects. They were not significantly different (P greater than 0.05). The mononuclear cells migration inhibition was also quite reproducible from day to day."} {"id": "PMID:1270811", "title": "Development of an enzyme immunoassay for human placental lactogen using labelled antibodies.", "content": "An immunoassay for the determination of human placental lactogen (HPL) has been developed using specific antibodies labelled with horseradish peroxidase. A method is presented in which the enzyme : antibody conjugate is purified with an antigenic solid phase to ensure the production of conjugates with intact immunological activity. Serum components interfere with the assay but this problem can only be avoided at the expense of a precise and practical assay for the determination of HPL.", "contents": "Development of an enzyme immunoassay for human placental lactogen using labelled antibodies. An immunoassay for the determination of human placental lactogen (HPL) has been developed using specific antibodies labelled with horseradish peroxidase. A method is presented in which the enzyme : antibody conjugate is purified with an antigenic solid phase to ensure the production of conjugates with intact immunological activity. Serum components interfere with the assay but this problem can only be avoided at the expense of a precise and practical assay for the determination of HPL."} {"id": "PMID:1270812", "title": "The antigen-binding capacity of serum IgG. An immunosorbent method applied to subtilisin as antigen.", "content": "A method for estimating the antigen-binding capacity of serum IgG is presented. A Sepharose anti-human IgG immunosorbent is incubated with test serum and washed. The antigen-binding capacity of the bound specific IgG is determined by incubation with purified, inactivated 125I-subtilisin. The method was applied tp the sera of workers in the detergent industry exposed to enzymatic preparations from Bacillus subtilis. The sera of 33 out of 69 workers bound a detectable amount of subtilisin, the detection limit ranging from 8--34 ng/ml in different assays. The amount of antigen bound ranged from 42--9380 ng/ml. IgG to subtilisin was not detected in the sera of 61 subjects with no known exposure to subtilisin and who were not factory workers.", "contents": "The antigen-binding capacity of serum IgG. An immunosorbent method applied to subtilisin as antigen. A method for estimating the antigen-binding capacity of serum IgG is presented. A Sepharose anti-human IgG immunosorbent is incubated with test serum and washed. The antigen-binding capacity of the bound specific IgG is determined by incubation with purified, inactivated 125I-subtilisin. The method was applied tp the sera of workers in the detergent industry exposed to enzymatic preparations from Bacillus subtilis. The sera of 33 out of 69 workers bound a detectable amount of subtilisin, the detection limit ranging from 8--34 ng/ml in different assays. The amount of antigen bound ranged from 42--9380 ng/ml. IgG to subtilisin was not detected in the sera of 61 subjects with no known exposure to subtilisin and who were not factory workers."} {"id": "PMID:1270813", "title": "Effects of sulfate concentration, electroendosmotic flow, and electrical resistance of agars and agaroses on counterimmunoelectrophoresis with adenovirus antigens and antisera.", "content": "The sulfate concentration, electroendosmosis (EE), and electrical resistance of 23 commonly used agars and agaroses were measured by standard techniques and related to counterimmunoeletrophoresis (CE) with adenovirus antigens and antisera. Statistical analyses of the test procedures themselves showed that the tests had sufficient reproducibility to warrant further analyses on the interaction or combined effects of these parameters on adenovirus CE tests. Both sulfate concentration and EE were related to CE by cubic polynomial equations; sulfate was directly related to EE by a linear equation. Resistance was somewhat linearly related to CE, but the differences among agars were too small to show a clear correlation. The data show that the fixed charges of the sulfate anion are major, although probably not the only, contributors to EE. The combines EE calculations from spectrophotometrically-scanned and hand-measured slides were used to predict the usefulness of new lots of agaroses for diagnostic adenovirus CE tests, according to the derived equation, CE score = 4.9 + 112.1 EE --397.1 EE2 + 329.1 EE3. The best stabilizing media for adenovirus CE tests had sulfate concentrations of 0.37% +/- 0.16% and EE cathodic mobility ratios of 0.17 +/- 0.03.", "contents": "Effects of sulfate concentration, electroendosmotic flow, and electrical resistance of agars and agaroses on counterimmunoelectrophoresis with adenovirus antigens and antisera. The sulfate concentration, electroendosmosis (EE), and electrical resistance of 23 commonly used agars and agaroses were measured by standard techniques and related to counterimmunoeletrophoresis (CE) with adenovirus antigens and antisera. Statistical analyses of the test procedures themselves showed that the tests had sufficient reproducibility to warrant further analyses on the interaction or combined effects of these parameters on adenovirus CE tests. Both sulfate concentration and EE were related to CE by cubic polynomial equations; sulfate was directly related to EE by a linear equation. Resistance was somewhat linearly related to CE, but the differences among agars were too small to show a clear correlation. The data show that the fixed charges of the sulfate anion are major, although probably not the only, contributors to EE. The combines EE calculations from spectrophotometrically-scanned and hand-measured slides were used to predict the usefulness of new lots of agaroses for diagnostic adenovirus CE tests, according to the derived equation, CE score = 4.9 + 112.1 EE --397.1 EE2 + 329.1 EE3. The best stabilizing media for adenovirus CE tests had sulfate concentrations of 0.37% +/- 0.16% and EE cathodic mobility ratios of 0.17 +/- 0.03."} {"id": "PMID:1270832", "title": "Selective action of hydrocortisone on postmitotic epidermal cells in vivo.", "content": "Hydrocortisone administered systemically for 3 weeks has no effect on any phase of epidermal cell proliferation as measured by autoradiographic methods. However, the speed of cell differentiation (maturation) is increased, resulting in a thinning of the living epidermis due to the shorter epidermal cell life. Comparison of the epidermis from two body sites (ear and sole of foot) in mice receiving 2.4 mug per gm body weight per day of hydrocortisone in drinking water for 3 weeks revealed no change in the labeling with [3H]thymidine, the mitotic indices, or the lengths of the cell cycle phases. Quantitation of the epidermal cell compartments showed that thinning of the epidermis with hydrocortisone was due to the loss of an identical number of differentiating epidermal cells per unit surface from both body sites. In both sites there was the same increased rate of maturation of postmitotic cells while the proliferative cell-pool remained unresponsive to the hormone. The alteration of the speed of cell maturation is the principal action of hydrocortisone in epidermis. The results indicate that the epidermal cellular concentration of, and the susceptibility to, the hormone were identical in ear and sole of foot despite the differing speeds of turnover of the two tissues.", "contents": "Selective action of hydrocortisone on postmitotic epidermal cells in vivo. Hydrocortisone administered systemically for 3 weeks has no effect on any phase of epidermal cell proliferation as measured by autoradiographic methods. However, the speed of cell differentiation (maturation) is increased, resulting in a thinning of the living epidermis due to the shorter epidermal cell life. Comparison of the epidermis from two body sites (ear and sole of foot) in mice receiving 2.4 mug per gm body weight per day of hydrocortisone in drinking water for 3 weeks revealed no change in the labeling with [3H]thymidine, the mitotic indices, or the lengths of the cell cycle phases. Quantitation of the epidermal cell compartments showed that thinning of the epidermis with hydrocortisone was due to the loss of an identical number of differentiating epidermal cells per unit surface from both body sites. In both sites there was the same increased rate of maturation of postmitotic cells while the proliferative cell-pool remained unresponsive to the hormone. The alteration of the speed of cell maturation is the principal action of hydrocortisone in epidermis. The results indicate that the epidermal cellular concentration of, and the susceptibility to, the hormone were identical in ear and sole of foot despite the differing speeds of turnover of the two tissues."} {"id": "PMID:1270833", "title": "Cytophotometric studies of epidermal proliferation in psoriatic and normal skin.", "content": "Cytophotometric measurements of single-cell DNA content were used to study human epidermal cell proliferation in vivo. It was found that Feulgen-DNA profiles can be used to assess proliferative activity in involved, uninvolved, and nonpsoriatic skin. Profiles of involved psoriatic skin were bimodal as is characteristic of actively proliferating populations. This was due to the presence of cells with twice (2C--presynthetic) or four times (4C--post-synthetic) the amount of DNA of the gametes, separated by the intermediate values of cells undergoing scheduled DNA synthesis. Profiles of uninvolved psoriatic as well as nonpsoriatic epidermis were unimodal with the majority of cells containing a 2C amount of DNA incating relatively low levels of proliferative activity. The observed variations in proliferative activity of these samples are discussed in terms of two alternative models. Since radioisotopes are not required, this technique presents a useful approach to studying human epidermal proliferation in vivo.", "contents": "Cytophotometric studies of epidermal proliferation in psoriatic and normal skin. Cytophotometric measurements of single-cell DNA content were used to study human epidermal cell proliferation in vivo. It was found that Feulgen-DNA profiles can be used to assess proliferative activity in involved, uninvolved, and nonpsoriatic skin. Profiles of involved psoriatic skin were bimodal as is characteristic of actively proliferating populations. This was due to the presence of cells with twice (2C--presynthetic) or four times (4C--post-synthetic) the amount of DNA of the gametes, separated by the intermediate values of cells undergoing scheduled DNA synthesis. Profiles of uninvolved psoriatic as well as nonpsoriatic epidermis were unimodal with the majority of cells containing a 2C amount of DNA incating relatively low levels of proliferative activity. The observed variations in proliferative activity of these samples are discussed in terms of two alternative models. Since radioisotopes are not required, this technique presents a useful approach to studying human epidermal proliferation in vivo."} {"id": "PMID:1270834", "title": "Ultraviolet light carcinogenesis in hairless mice: cell kinetics during induction and progression of squamous cell carcinoma as estimated by the double-labeling method.", "content": "The double-labeling method for studying cell cycle kinetics was applied to uninvolved epidermis of hairless mice (irradiated and unirradiated), and at various stages of ultraviolet light (UVL)-induced squamous cell carcinoma. The growth fraction (GF) was determined by continuous labeling with tritiated thymidine (3HTdR). The data indicate that the double-labeling technique is an acceptable method for studying cell kinetics in UVL-induced squamous cell carcinoma. The GF in normal epidermis (unirradiated and irradiated), hyperplastic epidermis, and lesions of squamous cell carcinoma is 1. The duration of cell generation (Tc) and DNA synthesis (Ts) periods decreased progressively with induction and progression of squamous cell carcinoma. For normal epidermis (irradiated mice) the Tc and Ts were 91 and 6.3 hr, respectively. In the hyperplastic epidermis, the Tc and Ts were reduced to 44 and 4.5 hr, respectively, while even lower values were obtained for the tumor (Tc = 16 hr, Ts = 3.1 hr). The labeling index (LI) in normal epidermis was 7% and increased progressively in hyperplastic epidermis (10%) and squamous cell carcinoma (19%). Epidermal cell differentiation in hyperplastic and tumor tissues appears to have been delayed (GF = 1), since cells above the basal layer, which in normal epidermis keratinize, retain the ability to proliferate, as evidenced by extensive incorporation of [3H]TdR in these cells. The results suggest that tumor production is associated with a progressive shortening of the cell cycle and delayed keratinization of epidermal cells.", "contents": "Ultraviolet light carcinogenesis in hairless mice: cell kinetics during induction and progression of squamous cell carcinoma as estimated by the double-labeling method. The double-labeling method for studying cell cycle kinetics was applied to uninvolved epidermis of hairless mice (irradiated and unirradiated), and at various stages of ultraviolet light (UVL)-induced squamous cell carcinoma. The growth fraction (GF) was determined by continuous labeling with tritiated thymidine (3HTdR). The data indicate that the double-labeling technique is an acceptable method for studying cell kinetics in UVL-induced squamous cell carcinoma. The GF in normal epidermis (unirradiated and irradiated), hyperplastic epidermis, and lesions of squamous cell carcinoma is 1. The duration of cell generation (Tc) and DNA synthesis (Ts) periods decreased progressively with induction and progression of squamous cell carcinoma. For normal epidermis (irradiated mice) the Tc and Ts were 91 and 6.3 hr, respectively. In the hyperplastic epidermis, the Tc and Ts were reduced to 44 and 4.5 hr, respectively, while even lower values were obtained for the tumor (Tc = 16 hr, Ts = 3.1 hr). The labeling index (LI) in normal epidermis was 7% and increased progressively in hyperplastic epidermis (10%) and squamous cell carcinoma (19%). Epidermal cell differentiation in hyperplastic and tumor tissues appears to have been delayed (GF = 1), since cells above the basal layer, which in normal epidermis keratinize, retain the ability to proliferate, as evidenced by extensive incorporation of [3H]TdR in these cells. The results suggest that tumor production is associated with a progressive shortening of the cell cycle and delayed keratinization of epidermal cells."} {"id": "PMID:1270835", "title": "A liquid film model of tetrakaidecahedral packing to account for the establishment of epidermal cell columns.", "content": "The possiblity that the organization of cells into columns in the mammalian epidermis may be a result of the close packing of these cells has been investigated in a model system involving the association of randomly produced soap bubbles into a stable froth. Upon floating to the surface of a liquid, soap bubbles have been found to spontaneously assemble into precise columns of interdigitating bubbles. The tetrakaidecahedral shape and the spatial configuration of these bubbles closely resemble those of stacked epidermal cells, although the columns of a froth were oriented at a 60degrees angle to their substratum rather than at right angles as occurs in the epidermal cell columns. These observations lend support to the theory that the organization of the cells in the epidermis into columns is due to the assumption of the keratocytes of a minimum surface-close packing array. Such an organizing mechanism would be independent of both positional control of the underlying mitoses and active guidance of the cells as they become superficially displaced within the epidermis. The observation that a high rate of cell turnover is incompatible with the epidermal column structure may be related to the finding that rapidly produced soap bubbles do not, at least initially, assemble into a columnar array.", "contents": "A liquid film model of tetrakaidecahedral packing to account for the establishment of epidermal cell columns. The possiblity that the organization of cells into columns in the mammalian epidermis may be a result of the close packing of these cells has been investigated in a model system involving the association of randomly produced soap bubbles into a stable froth. Upon floating to the surface of a liquid, soap bubbles have been found to spontaneously assemble into precise columns of interdigitating bubbles. The tetrakaidecahedral shape and the spatial configuration of these bubbles closely resemble those of stacked epidermal cells, although the columns of a froth were oriented at a 60degrees angle to their substratum rather than at right angles as occurs in the epidermal cell columns. These observations lend support to the theory that the organization of the cells in the epidermis into columns is due to the assumption of the keratocytes of a minimum surface-close packing array. Such an organizing mechanism would be independent of both positional control of the underlying mitoses and active guidance of the cells as they become superficially displaced within the epidermis. The observation that a high rate of cell turnover is incompatible with the epidermal column structure may be related to the finding that rapidly produced soap bubbles do not, at least initially, assemble into a columnar array."} {"id": "PMID:1270836", "title": "Natural synchrony of newborn mouse epidermal cells in vitro.", "content": "Epidermal cells were separated from newborn mouse skin and grown on glass chamber slides or in plastic Petri dishes. Cell proliferation was examined at short intervals during the first 3 to 4 days in culture. DNA synthesis was estimated by the incorporation of [3H]thymidine into epidermal DNA, or by the labeling index. The mitotic rate was estimated by blocking mitotic cells with vinblastine. Reasonable agreement was found with the different methods. The cells grew synchronously with peaks of DNA synthesis at 21 to 23 hr, 35 to 40 hr, and 60 hr; peak mitotic rates were seen at 44 to 48 hr and 72 to 76 hr. The cells appeared to grow exponentially during the first 3 to 4 days in culture, with one main cohort of cells dividing during the successive proliferative peaks.", "contents": "Natural synchrony of newborn mouse epidermal cells in vitro. Epidermal cells were separated from newborn mouse skin and grown on glass chamber slides or in plastic Petri dishes. Cell proliferation was examined at short intervals during the first 3 to 4 days in culture. DNA synthesis was estimated by the incorporation of [3H]thymidine into epidermal DNA, or by the labeling index. The mitotic rate was estimated by blocking mitotic cells with vinblastine. Reasonable agreement was found with the different methods. The cells grew synchronously with peaks of DNA synthesis at 21 to 23 hr, 35 to 40 hr, and 60 hr; peak mitotic rates were seen at 44 to 48 hr and 72 to 76 hr. The cells appeared to grow exponentially during the first 3 to 4 days in culture, with one main cohort of cells dividing during the successive proliferative peaks."} {"id": "PMID:1270837", "title": "Freeze-fracture of Langerhans granules. A comparative study.", "content": "A comparative study of freeze-fracture replicas and thin sections of Langerhans granules has proved that the effects of conventional tissue processing on the inner structure of the granule are negligible, and the study has confirmed the validity of the previously proposed tridimensional models. The paracrystalline quality of the substance contained between the limiting membranes of the disc-shaped area of the granules seems to suggest it protein nature. In replicas, no particle organizations attributable to intercellular junctions were observed on the plasma membranes of Langerhans cells.", "contents": "Freeze-fracture of Langerhans granules. A comparative study. A comparative study of freeze-fracture replicas and thin sections of Langerhans granules has proved that the effects of conventional tissue processing on the inner structure of the granule are negligible, and the study has confirmed the validity of the previously proposed tridimensional models. The paracrystalline quality of the substance contained between the limiting membranes of the disc-shaped area of the granules seems to suggest it protein nature. In replicas, no particle organizations attributable to intercellular junctions were observed on the plasma membranes of Langerhans cells."} {"id": "PMID:1270838", "title": "Organ culture of adult mouse esophageal mucosa in a defined medium.", "content": "A method is described for culturing adult mouse esophageal mucosa in a chemically defined medium. The preparation consists of mucosa and superficial submucosa. By light microscopy, autoradiography, and tritiated-thymidine [3H]TdR) uptake the tissue appears viable for at least 3 days. Although a drop in the rate of [3H]TdR uptake is observed in the initial hours of culture, recovery occurs by 24 hr and uptake remains constant for at least an additional 48 hr. Twenty-four-hour exposure to [3H]TdR and autoradiography reveals that 93 +/- 3% of the basal cells take up label; appreciable labeling is not found in other cells of the preparation. Pulse labeling indicated a transit time from basal layer to keratin layer of about 72 hr. This preparation should be useful for short-term in vitro studies of keratinized, stratified, squamous epithelium free of appendages and for studies of the growth properties of esophageal mucosa under simulated pathologic conditions.", "contents": "Organ culture of adult mouse esophageal mucosa in a defined medium. A method is described for culturing adult mouse esophageal mucosa in a chemically defined medium. The preparation consists of mucosa and superficial submucosa. By light microscopy, autoradiography, and tritiated-thymidine [3H]TdR) uptake the tissue appears viable for at least 3 days. Although a drop in the rate of [3H]TdR uptake is observed in the initial hours of culture, recovery occurs by 24 hr and uptake remains constant for at least an additional 48 hr. Twenty-four-hour exposure to [3H]TdR and autoradiography reveals that 93 +/- 3% of the basal cells take up label; appreciable labeling is not found in other cells of the preparation. Pulse labeling indicated a transit time from basal layer to keratin layer of about 72 hr. This preparation should be useful for short-term in vitro studies of keratinized, stratified, squamous epithelium free of appendages and for studies of the growth properties of esophageal mucosa under simulated pathologic conditions."} {"id": "PMID:1270839", "title": "Importance of pyrimidine nucleotide salvage pathways for DNA synthesis in skin.", "content": "Split-thickness rabbit skins were minced and incubated in vitro with radioactive precursors selected to measure do novo and salvage pathways for pyrimidine nucleotide synthesis. In this system, both the salvage precursors [3H]thymidine and [14C]cytidine were incorporated actively into skin DNA and only [14C]cytidine into skin RNA. In contrast, the de novo precursor [14C]orotic acid labeled skin RNA extensively but did not significantly label skin DNA. An unusually high ratio of specific activities of UMP:CMP in RNA was observed when [14C]orotic acid was used as a nucleotide precursor. Methotrexate effectively blocked thymidylate synthesis do novo but did not inhibit DNA synthesis as determined by [3H]thymidine incorporation into DNA thymidylate residues or by [14C]deoxycytidine incorporation into DNA deoxycytidylate residues. Azauridine inhibited labeling of RNA by [14C]orotic acid to a greater extent than labeling of DNA by [3H]thymidine. These results suggest that in rabbit skin, cytidine nucleotides are utilized more effectively than uridine nucleotides for deoxypyrimidine biosynthesis, that DNA synthesis is primarily dependent upon salvage mechanisms to supply deoxypyrimidine nucleotides, and that inhibition of thymidylate synthesis by methotrexate does not inhibit DNA synthesis in this system.", "contents": "Importance of pyrimidine nucleotide salvage pathways for DNA synthesis in skin. Split-thickness rabbit skins were minced and incubated in vitro with radioactive precursors selected to measure do novo and salvage pathways for pyrimidine nucleotide synthesis. In this system, both the salvage precursors [3H]thymidine and [14C]cytidine were incorporated actively into skin DNA and only [14C]cytidine into skin RNA. In contrast, the de novo precursor [14C]orotic acid labeled skin RNA extensively but did not significantly label skin DNA. An unusually high ratio of specific activities of UMP:CMP in RNA was observed when [14C]orotic acid was used as a nucleotide precursor. Methotrexate effectively blocked thymidylate synthesis do novo but did not inhibit DNA synthesis as determined by [3H]thymidine incorporation into DNA thymidylate residues or by [14C]deoxycytidine incorporation into DNA deoxycytidylate residues. Azauridine inhibited labeling of RNA by [14C]orotic acid to a greater extent than labeling of DNA by [3H]thymidine. These results suggest that in rabbit skin, cytidine nucleotides are utilized more effectively than uridine nucleotides for deoxypyrimidine biosynthesis, that DNA synthesis is primarily dependent upon salvage mechanisms to supply deoxypyrimidine nucleotides, and that inhibition of thymidylate synthesis by methotrexate does not inhibit DNA synthesis in this system."} {"id": "PMID:1270840", "title": "Testing the effects of fluids on rat skin using disposable polypropylene chambers.", "content": "Inexpensive, disposable polypropylene chambers for testing fluids on rat skin were made by removing the wings from polypropylene wing nuts and by cutting into the top of each nut a seat for an O-ring. Polypropylene screws with black heads were fabricated as seals for the chambers. After attachment to the backs of rats, these chambers provided a satisfactory means of keeping fluid in contact with the skin for 3 days.", "contents": "Testing the effects of fluids on rat skin using disposable polypropylene chambers. Inexpensive, disposable polypropylene chambers for testing fluids on rat skin were made by removing the wings from polypropylene wing nuts and by cutting into the top of each nut a seat for an O-ring. Polypropylene screws with black heads were fabricated as seals for the chambers. After attachment to the backs of rats, these chambers provided a satisfactory means of keeping fluid in contact with the skin for 3 days."} {"id": "PMID:1270872", "title": "Lead content of tissues of baby rats born of, and nourished by lead-poisoned mothers.", "content": "Three groups of Wistar rats (5 males and 5 females in each group) were given zero, 100 mg., and 200 mg. Pb(NO3) 2 per kilogram of body weight per day for 45 days and were mated. The lead feeding was continued throughout the duration of experiments. The blood and urinary lead, blood aminolevulinic acid dehydratase activity, and free erythrocyte protoporphyrin and urinary aminolevulinic acid were measured on these rats at the beginning of the study, at the time of mating, and prior to delivery. The tissues, incuding kidney, liver, heart, and brain of the newborn progeny were analyzed for lead content. The blood lead and aminolevulinic acid dehydratase were also measured (pooled blood). These tissues contained very high amounts of lead when the newborns were killed within half an hour after their birth, a very significant reduction being found after one day with further reduction after 7 days. Kidney and heart contained the highest amount of lead, the levels being dose-related. Three weeks after birth the lead content of tissues rose significantly but blood concentrations remained almost identical to the levels obtained 1 day after birth. There was no evidence of lead accumulation in the brain of the babies...", "contents": "Lead content of tissues of baby rats born of, and nourished by lead-poisoned mothers. Three groups of Wistar rats (5 males and 5 females in each group) were given zero, 100 mg., and 200 mg. Pb(NO3) 2 per kilogram of body weight per day for 45 days and were mated. The lead feeding was continued throughout the duration of experiments. The blood and urinary lead, blood aminolevulinic acid dehydratase activity, and free erythrocyte protoporphyrin and urinary aminolevulinic acid were measured on these rats at the beginning of the study, at the time of mating, and prior to delivery. The tissues, incuding kidney, liver, heart, and brain of the newborn progeny were analyzed for lead content. The blood lead and aminolevulinic acid dehydratase were also measured (pooled blood). These tissues contained very high amounts of lead when the newborns were killed within half an hour after their birth, a very significant reduction being found after one day with further reduction after 7 days. Kidney and heart contained the highest amount of lead, the levels being dose-related. Three weeks after birth the lead content of tissues rose significantly but blood concentrations remained almost identical to the levels obtained 1 day after birth. There was no evidence of lead accumulation in the brain of the babies..."} {"id": "PMID:1270874", "title": "Molecular size of rabbit C-reactive protein synthesized in vitro.", "content": "This study was performed to determine whether immunologically detectable C-reactive protein synthesized by rabbit liver mince in vitro is a micro- or macromolecular precursor of CRP, or if it is native CRP. Employing gel filtration and density gradient techniques, the molecular size of CRP newly synthesized by minced rabbit liver from inflamed rabbits was found identical with that of native CRP. Since no evidence for hepatic synthesis of a precursor can be shown, increased CRP formation after inflammation must result from increased de novo synthesis.", "contents": "Molecular size of rabbit C-reactive protein synthesized in vitro. This study was performed to determine whether immunologically detectable C-reactive protein synthesized by rabbit liver mince in vitro is a micro- or macromolecular precursor of CRP, or if it is native CRP. Employing gel filtration and density gradient techniques, the molecular size of CRP newly synthesized by minced rabbit liver from inflamed rabbits was found identical with that of native CRP. Since no evidence for hepatic synthesis of a precursor can be shown, increased CRP formation after inflammation must result from increased de novo synthesis."} {"id": "PMID:1270875", "title": "The relationship of serum ionized and total calcium in primary hyperparathyroidism.", "content": "Ionized and total calcium concentrations were measured in the same serum samples of 48 patients with primary hyperparathyroidism in order to compare diagnostic accuracy and sensitivity and to determine the intra-individual variation of these parameters in this disorder. In 149 samples, 0.7 per cent of serum ionized calcium and 7.4 per cent of total calcium determinations were within the normal range (mean +/- 2 S.D.). However, all patients exhibited abnormally elevated values upon repeated testing. Ionized and total calciums were significantly correlated both preoperatively (r=0.85 and p less than 0.001) and postoperatively (r greater than 0.9). Heterogeneous and abnormally large variations of both measurements were noted in these patients. It is concluded that the superior precision of the method for ionized calcium determination renders it more accurate than total calcium for the diagnosis of primary hyperparathyroidism. The disturbance of calcium homeostasis is reflected in both calcium and its ionic fraction in serum.", "contents": "The relationship of serum ionized and total calcium in primary hyperparathyroidism. Ionized and total calcium concentrations were measured in the same serum samples of 48 patients with primary hyperparathyroidism in order to compare diagnostic accuracy and sensitivity and to determine the intra-individual variation of these parameters in this disorder. In 149 samples, 0.7 per cent of serum ionized calcium and 7.4 per cent of total calcium determinations were within the normal range (mean +/- 2 S.D.). However, all patients exhibited abnormally elevated values upon repeated testing. Ionized and total calciums were significantly correlated both preoperatively (r=0.85 and p less than 0.001) and postoperatively (r greater than 0.9). Heterogeneous and abnormally large variations of both measurements were noted in these patients. It is concluded that the superior precision of the method for ionized calcium determination renders it more accurate than total calcium for the diagnosis of primary hyperparathyroidism. The disturbance of calcium homeostasis is reflected in both calcium and its ionic fraction in serum."} {"id": "PMID:1270876", "title": "Effect of acetazolamide on sodium reabsorption in the diluting segment in man.", "content": "The purpose of this study is to compare the effects of extracellular volume expansion (ECVE) and acetazolamide (ACTZ) on the transport of sodium in the diluting segment in man. All studies were performed at the peak of sustained oral water diuresis (Uosm. less than 75 mOsm. per kilogram). Distal delivery was estimated by the rate of urine flow and distal sodium reabsorption was approximated by the generation of free water. Free water clearance for given rates of distal delivery expressed as V(range 10 to 35 ml. per minute) was significantly lower and the clearance of sodium higher in the ACTZ group as compared with subjects with ECVE. However when CH2O was plotted against distal delivery expressed as CC1 + CH2O, no difference was detected between ACTZ and ECVE studies. We interpret these findings as suggesting that ACTZ does not have a direct inhibitory influence on the NaCl pump at the diluting site. Rather, the lowering of CH2O/V following ACTZ is due to the flooding of the diluting site with the poorly reabsorbable bicarbonate ion. Thus, the proximal action of ACTZ, which initiates urinary bicarbonate loss results secondarily in an apparent interference with the diluting mechanism in man.", "contents": "Effect of acetazolamide on sodium reabsorption in the diluting segment in man. The purpose of this study is to compare the effects of extracellular volume expansion (ECVE) and acetazolamide (ACTZ) on the transport of sodium in the diluting segment in man. All studies were performed at the peak of sustained oral water diuresis (Uosm. less than 75 mOsm. per kilogram). Distal delivery was estimated by the rate of urine flow and distal sodium reabsorption was approximated by the generation of free water. Free water clearance for given rates of distal delivery expressed as V(range 10 to 35 ml. per minute) was significantly lower and the clearance of sodium higher in the ACTZ group as compared with subjects with ECVE. However when CH2O was plotted against distal delivery expressed as CC1 + CH2O, no difference was detected between ACTZ and ECVE studies. We interpret these findings as suggesting that ACTZ does not have a direct inhibitory influence on the NaCl pump at the diluting site. Rather, the lowering of CH2O/V following ACTZ is due to the flooding of the diluting site with the poorly reabsorbable bicarbonate ion. Thus, the proximal action of ACTZ, which initiates urinary bicarbonate loss results secondarily in an apparent interference with the diluting mechanism in man."} {"id": "PMID:1270877", "title": "Correction of protein binding defect in uremic sera by charcoal treatment.", "content": "Protein binding of numerous drugs, primarily organic acids, is decreased in sera from uremic patients. The defect in binding is (1) greater than can be accounted for by hypoalbuminemia alone; (2) unchanged by prolonged in vitro dialysis; (3) transferred in the protein but not the ultrafiltrate fraction of uremic serum; and (4) not reproduced by addition of low and middle molecular weight compounds known to accumulate in uremia. However, treatment with activated charcoal at pH3 was found to significantly increase drug protein binding in uremic sera. This effect was studied with six different drugs in sera from groups of 6 normal subjects and 8 patients on chronic hemodialysis. The percentage of sulfamethoxazole, dicloxacillin, diphenylhydantoin, salicylate, and digitoxin bound to protein in normal sera (65.9, 97.1, 93.1, 96.7, and 92.7, respectively) was unchanged by charcoal treatment. In contrast, charcoal treatment significantly (p less than 0.01) increased the percentage of drug bound to protein in uremic sera from 41.7 to 59.0 for sulfamethoxazole, 90.7 to 96.3 for dicloxacillin, 84.3 to 90.8 for diphenyhydantoin, 86.4 to 93.8 for salicylate, and 89.5 to 90.9 for digitoxin. Charcoal treatment significantly (p less than 0.05) reduced penicillin protein binding in normal sera and failed to correct the binding defect for penicillin in uremic sera. The effect of charcoal can be explained by removal of an inhibitor which accumulates in uremia and (1) occupies the binding site of certain drugs, (2) changes the configuration of the albumin molecule, or (3) both. Free fatty acid (FFA) concentrations in uremic patients were similar to those in normal subjects and were not the cause of the binding defect.", "contents": "Correction of protein binding defect in uremic sera by charcoal treatment. Protein binding of numerous drugs, primarily organic acids, is decreased in sera from uremic patients. The defect in binding is (1) greater than can be accounted for by hypoalbuminemia alone; (2) unchanged by prolonged in vitro dialysis; (3) transferred in the protein but not the ultrafiltrate fraction of uremic serum; and (4) not reproduced by addition of low and middle molecular weight compounds known to accumulate in uremia. However, treatment with activated charcoal at pH3 was found to significantly increase drug protein binding in uremic sera. This effect was studied with six different drugs in sera from groups of 6 normal subjects and 8 patients on chronic hemodialysis. The percentage of sulfamethoxazole, dicloxacillin, diphenylhydantoin, salicylate, and digitoxin bound to protein in normal sera (65.9, 97.1, 93.1, 96.7, and 92.7, respectively) was unchanged by charcoal treatment. In contrast, charcoal treatment significantly (p less than 0.01) increased the percentage of drug bound to protein in uremic sera from 41.7 to 59.0 for sulfamethoxazole, 90.7 to 96.3 for dicloxacillin, 84.3 to 90.8 for diphenyhydantoin, 86.4 to 93.8 for salicylate, and 89.5 to 90.9 for digitoxin. Charcoal treatment significantly (p less than 0.05) reduced penicillin protein binding in normal sera and failed to correct the binding defect for penicillin in uremic sera. The effect of charcoal can be explained by removal of an inhibitor which accumulates in uremia and (1) occupies the binding site of certain drugs, (2) changes the configuration of the albumin molecule, or (3) both. Free fatty acid (FFA) concentrations in uremic patients were similar to those in normal subjects and were not the cause of the binding defect."} {"id": "PMID:1270878", "title": "A new iron-binding protein isolated from intestinal mucosa.", "content": "A new iron-binding protein contained in guinea pig intestinal mucosa has been purified to homogeneity. The protein has a molecular weight of 78,000 in a nondissociating system and 43,000 in SDS-gel electrophoresis. It binds approximately 2 moles of iron per mole with a formation constant of 10(19) at pH 7. It is distinguished from transferrin and lactoferrin by differences on DEAE-Sephadex chromatography and spectroscopy and by its failure to cross-react with antisera to these other iron-binding proteins.", "contents": "A new iron-binding protein isolated from intestinal mucosa. A new iron-binding protein contained in guinea pig intestinal mucosa has been purified to homogeneity. The protein has a molecular weight of 78,000 in a nondissociating system and 43,000 in SDS-gel electrophoresis. It binds approximately 2 moles of iron per mole with a formation constant of 10(19) at pH 7. It is distinguished from transferrin and lactoferrin by differences on DEAE-Sephadex chromatography and spectroscopy and by its failure to cross-react with antisera to these other iron-binding proteins."} {"id": "PMID:1270879", "title": "Effect of mannitol on phosphate transport in intact and acutely thyroparathyroidectomized rats.", "content": "Clearance experiments were performed in male Sprague-Dawley rats to determine the effect of mannitol on phosphate (Pi) transport. Solutions of 10 per cent mannitol or normal saline were infused at progressively increasing flow rates with or without parathyroid extract (PTE) infusion into the following animals: Group I: Intact Rats-Mannitol Infusion: A--Intact, hypocalcemic; B--Intact, normocalcemic, normomagnesemic; Group II: TPTX Rats: A--Mannitol infusion; B--Mannitol + PTE infusion; C--Hydropenia + PTE infusion; and D--Saline + PTE infusion. In contrast to previous reports, mannitol increased Pi excretion in intact rats. When Ca + Mg were maintained constant in intact rats or after TPTX, mannitol failed to increase Pi excretion. In TPTX rats receiving mannitol + PTE, increased Pi excretion was again noted. Comparison of Pi excretion during PTE infusion during hydropenia and volume expansion with mannitol or saline in TPTX rats revealed significantly higher Pi excretion with volume expansion. Pi excretion paralleled Na excretion in intact mannitol-loaded and PTE-infused TPTX animals undergoing a mannitol or saline diuresis. Pi and Na excretions, however, were dissociated in mannitol-loaded TPTX rats, intact animals receiving simultaneous Ca and Mg infusion, and TPTX hydropenic animals receiving PTE. These studies indicate that (1) mannitol increases Pi excretion in intact rat, (2) the phosphaturia is PTH-mediated, (3) Pi and Na excretions can be dissociated, and (4) volume expansion with either mannitol or saline enhances the effect of PTH on Pi transport in the renal tubule.", "contents": "Effect of mannitol on phosphate transport in intact and acutely thyroparathyroidectomized rats. Clearance experiments were performed in male Sprague-Dawley rats to determine the effect of mannitol on phosphate (Pi) transport. Solutions of 10 per cent mannitol or normal saline were infused at progressively increasing flow rates with or without parathyroid extract (PTE) infusion into the following animals: Group I: Intact Rats-Mannitol Infusion: A--Intact, hypocalcemic; B--Intact, normocalcemic, normomagnesemic; Group II: TPTX Rats: A--Mannitol infusion; B--Mannitol + PTE infusion; C--Hydropenia + PTE infusion; and D--Saline + PTE infusion. In contrast to previous reports, mannitol increased Pi excretion in intact rats. When Ca + Mg were maintained constant in intact rats or after TPTX, mannitol failed to increase Pi excretion. In TPTX rats receiving mannitol + PTE, increased Pi excretion was again noted. Comparison of Pi excretion during PTE infusion during hydropenia and volume expansion with mannitol or saline in TPTX rats revealed significantly higher Pi excretion with volume expansion. Pi excretion paralleled Na excretion in intact mannitol-loaded and PTE-infused TPTX animals undergoing a mannitol or saline diuresis. Pi and Na excretions, however, were dissociated in mannitol-loaded TPTX rats, intact animals receiving simultaneous Ca and Mg infusion, and TPTX hydropenic animals receiving PTE. These studies indicate that (1) mannitol increases Pi excretion in intact rat, (2) the phosphaturia is PTH-mediated, (3) Pi and Na excretions can be dissociated, and (4) volume expansion with either mannitol or saline enhances the effect of PTH on Pi transport in the renal tubule."} {"id": "PMID:1270880", "title": "Chemotherapy of experimental streptococcal endocarditis. V. Effect of duration of infection and retained intracardiac catheter on response to treatment.", "content": "The dynamics of infection and response to penicillin G (P) or combined P plus streptomycin (S) therapy were studied in a rabbit model of penicillin-sensitive Streptococcus sanguis endocarditis. Increased delay between infection and initiation of treatment required longer duration of therapy to effect a cure. Irrespective of the interval between infection and onset of therapy, P combined with S regularly eliminated streptococci from endocardial vegetations more rapidly than P alone, both in the presence and absence of an intracardiac catheter--although the difference in response was more marked with the catheter present. The combination of P and S consistently showed superior in vivo bactericidal activity compared to P alone in established S. sanguis endocarditis.", "contents": "Chemotherapy of experimental streptococcal endocarditis. V. Effect of duration of infection and retained intracardiac catheter on response to treatment. The dynamics of infection and response to penicillin G (P) or combined P plus streptomycin (S) therapy were studied in a rabbit model of penicillin-sensitive Streptococcus sanguis endocarditis. Increased delay between infection and initiation of treatment required longer duration of therapy to effect a cure. Irrespective of the interval between infection and onset of therapy, P combined with S regularly eliminated streptococci from endocardial vegetations more rapidly than P alone, both in the presence and absence of an intracardiac catheter--although the difference in response was more marked with the catheter present. The combination of P and S consistently showed superior in vivo bactericidal activity compared to P alone in established S. sanguis endocarditis."} {"id": "PMID:1270881", "title": "Inhibition of platelet aggregation by 5-nitro-2-furaldehyde diacetate with observations on structure-activity relationships.", "content": "Nitrofurantoin [1-(5'-nitro-2'-furfurylideneamino)-2, 4-diketoimidazole] is a potent inhibitor of primary ADP-induced platelet aggregation. The nitro group on the furan ring and the specific arrangement of the two keto groups on the imidazole ring are the molecular characteristics of nitrofurantoin critical to its inhibitory effect. The present studies report that 5-nitro-2-furaldehyde diacetate is also a potent inhibitor of primary ADP-induced platelet aggregation. 5-Nitro-2-furaldehyde diproprionate, 5-nitro-2-furaldehyde dibutyrate, and 5-nitro-2-furfuryl acetate are essentially inactive. These results indicate that a diacetate moiety can replace the diketoimidazole moiety of nitrofurantoin and form a compound that fully retains the inhibitory effect upon primary ADP-induced platelet aggregation.", "contents": "Inhibition of platelet aggregation by 5-nitro-2-furaldehyde diacetate with observations on structure-activity relationships. Nitrofurantoin [1-(5'-nitro-2'-furfurylideneamino)-2, 4-diketoimidazole] is a potent inhibitor of primary ADP-induced platelet aggregation. The nitro group on the furan ring and the specific arrangement of the two keto groups on the imidazole ring are the molecular characteristics of nitrofurantoin critical to its inhibitory effect. The present studies report that 5-nitro-2-furaldehyde diacetate is also a potent inhibitor of primary ADP-induced platelet aggregation. 5-Nitro-2-furaldehyde diproprionate, 5-nitro-2-furaldehyde dibutyrate, and 5-nitro-2-furfuryl acetate are essentially inactive. These results indicate that a diacetate moiety can replace the diketoimidazole moiety of nitrofurantoin and form a compound that fully retains the inhibitory effect upon primary ADP-induced platelet aggregation."} {"id": "PMID:1270882", "title": "Drift in the oxygen content measured with the Lex-O2-Con: long-term assessment.", "content": "After more than one year of intensive use (30 to 50 measurements a day) a drift was observed in the data given by two Lex-O2-Con analyzers. This was confirmed by iterative comparisons with the Van Slyke method. After recharge of the cells, the instruments seem to function again correctly.", "contents": "Drift in the oxygen content measured with the Lex-O2-Con: long-term assessment. After more than one year of intensive use (30 to 50 measurements a day) a drift was observed in the data given by two Lex-O2-Con analyzers. This was confirmed by iterative comparisons with the Van Slyke method. After recharge of the cells, the instruments seem to function again correctly."} {"id": "PMID:1270883", "title": "A radioimmunoassay to determine the subtypes D and Y of the hepatitis-B surface antigen.", "content": "A radioimmunologic test system for determining the subtypes D and Y of the hepatitis-B surface antigen (HBs-Ag, Australia antigen, HAA) is described. This technique uses the immunoadsorption principle. The antigen to be subtyped is incubated with an antiserum which contains (125)I-labeled antibodies to the antigenic determinants a, d, and y. The specificity of the antibody which is not consumed in forming the antigen-antibody complex is determined by absorption on agarose to which HBs-Ag of subtypes D and Y is coupled. This specificity permits conclusions as to the subtype of the hepatitis-B surface antigen which is being investigated.", "contents": "A radioimmunoassay to determine the subtypes D and Y of the hepatitis-B surface antigen. A radioimmunologic test system for determining the subtypes D and Y of the hepatitis-B surface antigen (HBs-Ag, Australia antigen, HAA) is described. This technique uses the immunoadsorption principle. The antigen to be subtyped is incubated with an antiserum which contains (125)I-labeled antibodies to the antigenic determinants a, d, and y. The specificity of the antibody which is not consumed in forming the antigen-antibody complex is determined by absorption on agarose to which HBs-Ag of subtypes D and Y is coupled. This specificity permits conclusions as to the subtype of the hepatitis-B surface antigen which is being investigated."} {"id": "PMID:1270885", "title": "Effect of simultaneous thiamin and riboflavin deficiencies on the determination of transketolase and glutathione reductase.", "content": "Thiamin and/or riboflavin status have been assessed in rats simultaneously deprived of both vitamins and subsequently repleated with either one or the other in succession. Undernutrition in control rats was found to depress the activity of the erythrocyte enzymes (transketolase and glutathione reductase, respectively) used to assess status. On the other hand, the activity coefficients obtained by in vitro stimulation of the enzymes with their respective missing cofactors were not suppressed. Therefore the activity coefficients were superior indices of thiamin and riboflavin nutriture compared to the enzyme activities. When activity coefficients were used as the indices of vitamin status there did not appear to be interference from the simultaneous deficiency of the alternate vitamin. Apparent interference was encountered when the enzyme activity itself was used as the criteria.", "contents": "Effect of simultaneous thiamin and riboflavin deficiencies on the determination of transketolase and glutathione reductase. Thiamin and/or riboflavin status have been assessed in rats simultaneously deprived of both vitamins and subsequently repleated with either one or the other in succession. Undernutrition in control rats was found to depress the activity of the erythrocyte enzymes (transketolase and glutathione reductase, respectively) used to assess status. On the other hand, the activity coefficients obtained by in vitro stimulation of the enzymes with their respective missing cofactors were not suppressed. Therefore the activity coefficients were superior indices of thiamin and riboflavin nutriture compared to the enzyme activities. When activity coefficients were used as the indices of vitamin status there did not appear to be interference from the simultaneous deficiency of the alternate vitamin. Apparent interference was encountered when the enzyme activity itself was used as the criteria."} {"id": "PMID:1270886", "title": "The effect of uremia on penicillin flux between blood and cerebrospinal fluid.", "content": "The effect of uremia on the choroid plexus system responsible for transport of penicillin from cerebrospinal fluid (CSF) to blood was studied in vitro and in vivo. Uremia was induced in rabbits by injecting toxic doses of cephaloridine or by obstructing urine flow. Three days after the induction of uremia, isolated choroid plexuses from normal rabbits were unable to concentrate penicillin 14C normally when incubated in either CSF or ultrafiltrates of plasma from uremic rabbits. In vivo, a decrease in the disappearance of penicillin 14C from CSF was observed in uremic rabbits. However, the choroid plexus transport system for penicillin was only partially and reversibly depressed in uremia. The increased CSF levels of penicillin uremia are due to: decreased excretion of penicillin by the kidney, depression of active efflux of penicillin from the CSF, and decreased plasma binding of penicillin.", "contents": "The effect of uremia on penicillin flux between blood and cerebrospinal fluid. The effect of uremia on the choroid plexus system responsible for transport of penicillin from cerebrospinal fluid (CSF) to blood was studied in vitro and in vivo. Uremia was induced in rabbits by injecting toxic doses of cephaloridine or by obstructing urine flow. Three days after the induction of uremia, isolated choroid plexuses from normal rabbits were unable to concentrate penicillin 14C normally when incubated in either CSF or ultrafiltrates of plasma from uremic rabbits. In vivo, a decrease in the disappearance of penicillin 14C from CSF was observed in uremic rabbits. However, the choroid plexus transport system for penicillin was only partially and reversibly depressed in uremia. The increased CSF levels of penicillin uremia are due to: decreased excretion of penicillin by the kidney, depression of active efflux of penicillin from the CSF, and decreased plasma binding of penicillin."} {"id": "PMID:1270887", "title": "A new approach to quantitation of the various sources of bilrubin in man.", "content": "Studies of the \"early labeling\" of fecal bile pigment have been widely interpreted as indicating that 10 to 20 per cent of total bile pigment production in normal man is derived from the processes which give rise to the \"early labeled\" pigment peak (ELP). However, this conclusion is based on a very small number of studies with inherent experimental and analytic limitations. In the present study, a new experimental approach was employed. Plasma bilirubin turnover (BRT), total red blood cell volume (TRCV), and red cell survival were measured in 26 normal volunteers and 35 patients with various hepatic and/or hematologic disorders. The quantity of bilirubin derived from red blood cell degradation (BRRBC) was calculated from TRCV and the mean red cell life-span, and the difference between BRT and BRRBC, designated \"excess bilirubin synthesis (EBS),\" was considered to represent the quantity of bilirubin derived from the processes responsible for ELP. In normal volunteer subjects, EBS averaged 1.0 mg. per kilogram per day, and accounted for 25 per cent of daily bilirubin turnover. Hence, results derived by this approach exceeded the range estimated from analysis of \"early labeled peak\" data. Further analysis of the data in terms of a simple model of bilirubin sources was compatible with the hypothesis that EBS consists of an essentially constant component, averaging 0.8 mg. per kilogram per day, presumably derived principally from the liver, and a second component which varies with the erthropoietic rate. Hence, in normal man the liver may contribute the major fraction of EBS.", "contents": "A new approach to quantitation of the various sources of bilrubin in man. Studies of the \"early labeling\" of fecal bile pigment have been widely interpreted as indicating that 10 to 20 per cent of total bile pigment production in normal man is derived from the processes which give rise to the \"early labeled\" pigment peak (ELP). However, this conclusion is based on a very small number of studies with inherent experimental and analytic limitations. In the present study, a new experimental approach was employed. Plasma bilirubin turnover (BRT), total red blood cell volume (TRCV), and red cell survival were measured in 26 normal volunteers and 35 patients with various hepatic and/or hematologic disorders. The quantity of bilirubin derived from red blood cell degradation (BRRBC) was calculated from TRCV and the mean red cell life-span, and the difference between BRT and BRRBC, designated \"excess bilirubin synthesis (EBS),\" was considered to represent the quantity of bilirubin derived from the processes responsible for ELP. In normal volunteer subjects, EBS averaged 1.0 mg. per kilogram per day, and accounted for 25 per cent of daily bilirubin turnover. Hence, results derived by this approach exceeded the range estimated from analysis of \"early labeled peak\" data. Further analysis of the data in terms of a simple model of bilirubin sources was compatible with the hypothesis that EBS consists of an essentially constant component, averaging 0.8 mg. per kilogram per day, presumably derived principally from the liver, and a second component which varies with the erthropoietic rate. Hence, in normal man the liver may contribute the major fraction of EBS."} {"id": "PMID:1270888", "title": "Changes in the ratio of plasma to intersitiial fluid volume during long-term antihypertensive therapy.", "content": "Based on determinations of plasma (T-1824)(PV) and extracellular fluid volumes (82Br- distribution space) (ECFV), the PV/IF ratio (IF=ECFV.PV) was calculated three times with a 1-week interval between determinations in untreated patients with essential hypertension. During treatment with hydrochlorothiazide (13 males and 8 females), hydrochlorothiazide-triamterne (5 males and 5 females), hydrochlorothiazide-alpha-methyldopa (7 males and 4 females), and propranolol (6 males and 4 females), PV/IF was determined after 2 to 6 months of treatment. PV/IF was significantly reduced during hydrochlorothiazide treatment (delta PV/IF:--0.011, S.D.: 0.011, p is less than 0.001) and propranolol treatment (delta PV/IF:--0.017, S.D.: 0.022, p is less than 0.05), remained unchanged during hydrochlorothiazide-triamterene treatment and increased significantly during hydrochlorothiazide-alpha-methyldopa treatment (deltaPV/IF: .013, S.D.: 0.015, p is less than 0.05). There was a negative correlation between PV/IF and mean blood pressure during hydrochlorothiazide treatment (r:--0.49, n: 21, p is less than 0.05 (and hydrochlorothiazide-triamterene treatment (r:--0.79, n: 10, p is less than 0.01), whereas no correlation was found during treatment with hydrochlorothiazide-alpha-methyldopa or propranolol. Correlation between mean blood pressure and the individual volumes was not observed nor was there any correlation between changes in the parameters investigated. It is concluded that PV/IF is more accurately correlated to mean blood pressure than are the individual volumes and that, during long-term antihypertensive treatment, PV/IF will reflect changes in the tone of the capacitance vessels and the venous resistance vessels, resulting in a changed equilibrium between the intravascular and the interstitial volumes. It is suggested that the reduction in PV/IF during thiazide and propranolol therapy is related to a relative increase in venoconstrictor sympathetic activity whereas the increase in PV/IF by alpha-methyldopa is caused by decreased sympathetic tone and venodilation.", "contents": "Changes in the ratio of plasma to intersitiial fluid volume during long-term antihypertensive therapy. Based on determinations of plasma (T-1824)(PV) and extracellular fluid volumes (82Br- distribution space) (ECFV), the PV/IF ratio (IF=ECFV.PV) was calculated three times with a 1-week interval between determinations in untreated patients with essential hypertension. During treatment with hydrochlorothiazide (13 males and 8 females), hydrochlorothiazide-triamterne (5 males and 5 females), hydrochlorothiazide-alpha-methyldopa (7 males and 4 females), and propranolol (6 males and 4 females), PV/IF was determined after 2 to 6 months of treatment. PV/IF was significantly reduced during hydrochlorothiazide treatment (delta PV/IF:--0.011, S.D.: 0.011, p is less than 0.001) and propranolol treatment (delta PV/IF:--0.017, S.D.: 0.022, p is less than 0.05), remained unchanged during hydrochlorothiazide-triamterene treatment and increased significantly during hydrochlorothiazide-alpha-methyldopa treatment (deltaPV/IF: .013, S.D.: 0.015, p is less than 0.05). There was a negative correlation between PV/IF and mean blood pressure during hydrochlorothiazide treatment (r:--0.49, n: 21, p is less than 0.05 (and hydrochlorothiazide-triamterene treatment (r:--0.79, n: 10, p is less than 0.01), whereas no correlation was found during treatment with hydrochlorothiazide-alpha-methyldopa or propranolol. Correlation between mean blood pressure and the individual volumes was not observed nor was there any correlation between changes in the parameters investigated. It is concluded that PV/IF is more accurately correlated to mean blood pressure than are the individual volumes and that, during long-term antihypertensive treatment, PV/IF will reflect changes in the tone of the capacitance vessels and the venous resistance vessels, resulting in a changed equilibrium between the intravascular and the interstitial volumes. It is suggested that the reduction in PV/IF during thiazide and propranolol therapy is related to a relative increase in venoconstrictor sympathetic activity whereas the increase in PV/IF by alpha-methyldopa is caused by decreased sympathetic tone and venodilation."} {"id": "PMID:1270889", "title": "Vitamin B6 status of young men, women, and women using oral contraceptives.", "content": "Vitamin B6 intakes of 33 males, 73 females, and 46 females using oral contraceptives, all 18- to 25-year-old students, were compared to coenzyme stimulation of erythrocyte alanine aminotransferase activities of blood samples obtained from these subjects in order to ascertain the vitamin B6 status and perhaps the requirements of this population group. Trained interviewers obtained 24-hour recalls; subjects supplied 2-day food records. Dietary record analyses revealed that students reported consuming slightly less kilocalories, more protein, and considerably less vitamin B6 than the 1974 recommended dietary allowances. Erthrocyte alanine aminotransferase activities, with and without additional coenzyme, of blood samples from the 3 groups were significantly different from each other; per cent coenzyme stimulation of enzymatic activity of females and females on oral contraceptives were significantly different from each other. Enzyme data were not significantly affected by race, age, income, food budget, preparation of own food, frequency of eating out, or vitamin supplementation. Several subjects in all 3 groups had high per cent stimulation values which is considered to be indicative of subclinical vitamin B6 deficiency. Subjects with values near 0 per cent stimulation had varying vitamin B6 intakes thus perhaps indicating large individual variations in vitamin B6 requirements.", "contents": "Vitamin B6 status of young men, women, and women using oral contraceptives. Vitamin B6 intakes of 33 males, 73 females, and 46 females using oral contraceptives, all 18- to 25-year-old students, were compared to coenzyme stimulation of erythrocyte alanine aminotransferase activities of blood samples obtained from these subjects in order to ascertain the vitamin B6 status and perhaps the requirements of this population group. Trained interviewers obtained 24-hour recalls; subjects supplied 2-day food records. Dietary record analyses revealed that students reported consuming slightly less kilocalories, more protein, and considerably less vitamin B6 than the 1974 recommended dietary allowances. Erthrocyte alanine aminotransferase activities, with and without additional coenzyme, of blood samples from the 3 groups were significantly different from each other; per cent coenzyme stimulation of enzymatic activity of females and females on oral contraceptives were significantly different from each other. Enzyme data were not significantly affected by race, age, income, food budget, preparation of own food, frequency of eating out, or vitamin supplementation. Several subjects in all 3 groups had high per cent stimulation values which is considered to be indicative of subclinical vitamin B6 deficiency. Subjects with values near 0 per cent stimulation had varying vitamin B6 intakes thus perhaps indicating large individual variations in vitamin B6 requirements."} {"id": "PMID:1270890", "title": "Determinants of deranged sodium and water homeostasis in decompensated cirrhosis.", "content": "Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI) results in a significant natriuresis, kaliuresis, and diuresis. The NI model was utilized to assess the role of \"effective volume\" and hyperaldosteronism in the impairment of sodium and water handling in cirrhosis. Eleven cirrhotic patients were studied twice while in balance on a 10 mEq. Na, 100 mEq. K diet: control and NI. The conditions of seated posture and time of day were identical. UNaV was constant throughout C, ranging from 1 to 2 muEq per minute. During NI, UNaV increased progressively from 1 +/- 1 (S.E.M.) during the prestudy hour to 89 +/- 32 muEq per minute during hour 5 of NI (p less than 0.02), greatly exceeding the comparable value found in normal subjects on an identical diet. (See article).", "contents": "Determinants of deranged sodium and water homeostasis in decompensated cirrhosis. Previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant central hypervolemia induced by water immersion to the neck (NI) results in a significant natriuresis, kaliuresis, and diuresis. The NI model was utilized to assess the role of \"effective volume\" and hyperaldosteronism in the impairment of sodium and water handling in cirrhosis. Eleven cirrhotic patients were studied twice while in balance on a 10 mEq. Na, 100 mEq. K diet: control and NI. The conditions of seated posture and time of day were identical. UNaV was constant throughout C, ranging from 1 to 2 muEq per minute. During NI, UNaV increased progressively from 1 +/- 1 (S.E.M.) during the prestudy hour to 89 +/- 32 muEq per minute during hour 5 of NI (p less than 0.02), greatly exceeding the comparable value found in normal subjects on an identical diet. (See article)."} {"id": "PMID:1270891", "title": "Combined pre-immunization and granulocyte transfusion therapy for treatment of pseudomonas septicemia in neutropenic dogs.", "content": "An experimental model was designed to evaluate a combined protocol of active immunization and granulocyte transfusions for treatment of Pseudomonas aeruginosa sepsis in the neutropenic host. One member of a pair of dogs was immunized with P. aeruginosa vaccine. Both dogs were then rendered transiently neutropenic with a single intravenous dose of cyclophosphamide (40 mg. per kilogram) and challenged with an intravenous inoculum of P. aeruginosa. Twenty-four and 48 hours after pseudomonas challenge each animal received granulocyte transfusions. Effectiveness of therapy was evaluated by observation of survival time, febrile response, and quantitative blood cultures. Results showed a significant increase in the survival period (P is less than 0.05), a lower febrile response (P is less than 0.025), negative blood cultures, and a greater recovery rate in the immune group. Immune dogs that died had negative blood cultures or less than or equal to 10 pseudomonas per milliliter of blood despite the presence of P. aeruginosa in tissues. In contrast, control dogs had septic deaths within 67 hours of pseudomonas challenge, marked febrile responses with 24 hours of infection, and positive blood cultures with 4,000 to 25,800 pseudomonas per milliliter of blood. These data show that combined therapy with immunization and granulocyte transfusions is effective in reducing the severity of P. aeruginosa infection and in preventing bacteremia during periods of leukopenia.", "contents": "Combined pre-immunization and granulocyte transfusion therapy for treatment of pseudomonas septicemia in neutropenic dogs. An experimental model was designed to evaluate a combined protocol of active immunization and granulocyte transfusions for treatment of Pseudomonas aeruginosa sepsis in the neutropenic host. One member of a pair of dogs was immunized with P. aeruginosa vaccine. Both dogs were then rendered transiently neutropenic with a single intravenous dose of cyclophosphamide (40 mg. per kilogram) and challenged with an intravenous inoculum of P. aeruginosa. Twenty-four and 48 hours after pseudomonas challenge each animal received granulocyte transfusions. Effectiveness of therapy was evaluated by observation of survival time, febrile response, and quantitative blood cultures. Results showed a significant increase in the survival period (P is less than 0.05), a lower febrile response (P is less than 0.025), negative blood cultures, and a greater recovery rate in the immune group. Immune dogs that died had negative blood cultures or less than or equal to 10 pseudomonas per milliliter of blood despite the presence of P. aeruginosa in tissues. In contrast, control dogs had septic deaths within 67 hours of pseudomonas challenge, marked febrile responses with 24 hours of infection, and positive blood cultures with 4,000 to 25,800 pseudomonas per milliliter of blood. These data show that combined therapy with immunization and granulocyte transfusions is effective in reducing the severity of P. aeruginosa infection and in preventing bacteremia during periods of leukopenia."} {"id": "PMID:1270892", "title": "A three-month survival of a calf with an artificial heart.", "content": "An artificial heart constructed from Biomer, a polyurethane, kept a calf alive for more than three months after its natural heart was removed. During this time all of the calf's vital organs apparently functioned well. We had been able to keep similar animals alive with Jarvik III hearts made from Silastic for one month. The principal problem encountered was the infection centering along the compressed air drive lines to the artificial heart. Another problem is thrombus formation in the artificial heart. Redesigning of the artificial ventricles to improve flow patterns and reduce material discontinuities should be attempted to eliminate localized thrombus formation within the ventricles. The rapid growth of the calf has led us to examine the possibility of alternative animal models for future long-term experiments. The most encouraging aspects of this experiment were the long survival time of the calf and the very low level of blood damage caused by the artificial heart.", "contents": "A three-month survival of a calf with an artificial heart. An artificial heart constructed from Biomer, a polyurethane, kept a calf alive for more than three months after its natural heart was removed. During this time all of the calf's vital organs apparently functioned well. We had been able to keep similar animals alive with Jarvik III hearts made from Silastic for one month. The principal problem encountered was the infection centering along the compressed air drive lines to the artificial heart. Another problem is thrombus formation in the artificial heart. Redesigning of the artificial ventricles to improve flow patterns and reduce material discontinuities should be attempted to eliminate localized thrombus formation within the ventricles. The rapid growth of the calf has led us to examine the possibility of alternative animal models for future long-term experiments. The most encouraging aspects of this experiment were the long survival time of the calf and the very low level of blood damage caused by the artificial heart."} {"id": "PMID:1270893", "title": "Procoagulant and platelet aggregating properties of antilymphocyte sera.", "content": "Ten anti-human lymphocyte sera in clinical use at six transplant centers and five anti-nonhuman lymphocyte sera were studied for their procoagulant and platelet-aggregating properties. This investigation was initiated following the observation of a clinical episode of renal artery thrombosis, associated with the use of one of the sera in a patient who had received a cadaveric renal transplant. The procoagulant from this serum shortened the clotting times of individual samples deficient, respectively, in factors XII, XI IX, X VIII, and VII. Esterolytic activity, demonstrated on the substrate benzoylarginine ethyl ester, was completely inhibited by phenylmethylsulfonyl fluoride, but coagulant activity was variably affected. The platelet-aggregating activity (PAA) has been identified as a complement-fixing gamma G antibody that was absorbed from the antilymphocyte serum (ALS) with human spleen lymphocytes. Five of the ten anti-human lymphocyte sera showed varying procoagulant activity (PCA), and six sera demonstrated PAA. Three sera contained both activities. The presence of both PCA and PAA in the same preparation may predispose patients to thrombotic events, particularly if administered intravenously. Sera should be screened for PCA and PAA prior to clinical use, and sera with these properties should be used with caution.", "contents": "Procoagulant and platelet aggregating properties of antilymphocyte sera. Ten anti-human lymphocyte sera in clinical use at six transplant centers and five anti-nonhuman lymphocyte sera were studied for their procoagulant and platelet-aggregating properties. This investigation was initiated following the observation of a clinical episode of renal artery thrombosis, associated with the use of one of the sera in a patient who had received a cadaveric renal transplant. The procoagulant from this serum shortened the clotting times of individual samples deficient, respectively, in factors XII, XI IX, X VIII, and VII. Esterolytic activity, demonstrated on the substrate benzoylarginine ethyl ester, was completely inhibited by phenylmethylsulfonyl fluoride, but coagulant activity was variably affected. The platelet-aggregating activity (PAA) has been identified as a complement-fixing gamma G antibody that was absorbed from the antilymphocyte serum (ALS) with human spleen lymphocytes. Five of the ten anti-human lymphocyte sera showed varying procoagulant activity (PCA), and six sera demonstrated PAA. Three sera contained both activities. The presence of both PCA and PAA in the same preparation may predispose patients to thrombotic events, particularly if administered intravenously. Sera should be screened for PCA and PAA prior to clinical use, and sera with these properties should be used with caution."} {"id": "PMID:1270894", "title": "The measurement of rates of mineral loss with aging.", "content": "The photon absorption technique was used to measure bone mineral content in the radius repeatedly with time to determine the feasibility of using this method in studies on the rate of loss with aging. Two groups of postmenopausal women were followed, a younger group for an average of 3.74 years and an older group for an average of 2.37 years. It was determined that estimates of rate over periods less than two years were too low in precision to be useful. There were significant differences in rates among individuals. The loss of mineral from the midshaft site was determined to be linear within the precision of the method and over an average interval of 3.74 years. From these data the size of groups and length of time needed for a study to determine the effect of a treatment upon inhibition of bone loss was predicted. When the inhibition is 50 per cent of the control rate, it would be possible to detect a significant (alpha=0.05) inhibition with a certainty of 95 per cent (1-beta = 0.95), if 56 subjects were followed in each group for a period averaging 2.70 years. A more potent inhibition or more frequent visits would reduce the number of subjects and duration of study needed. The separation of individuals into groups of significantly more rapid and slower rates of loss was demonstrated. From these data, it is possible to predict that one-third of a sample could be so characterized after 3.5 years. The photon absorption technique can be applied to the measurement of the rate of loss of mineral with aging with a precision that is sufficicient for certain types of clinical investigations.", "contents": "The measurement of rates of mineral loss with aging. The photon absorption technique was used to measure bone mineral content in the radius repeatedly with time to determine the feasibility of using this method in studies on the rate of loss with aging. Two groups of postmenopausal women were followed, a younger group for an average of 3.74 years and an older group for an average of 2.37 years. It was determined that estimates of rate over periods less than two years were too low in precision to be useful. There were significant differences in rates among individuals. The loss of mineral from the midshaft site was determined to be linear within the precision of the method and over an average interval of 3.74 years. From these data the size of groups and length of time needed for a study to determine the effect of a treatment upon inhibition of bone loss was predicted. When the inhibition is 50 per cent of the control rate, it would be possible to detect a significant (alpha=0.05) inhibition with a certainty of 95 per cent (1-beta = 0.95), if 56 subjects were followed in each group for a period averaging 2.70 years. A more potent inhibition or more frequent visits would reduce the number of subjects and duration of study needed. The separation of individuals into groups of significantly more rapid and slower rates of loss was demonstrated. From these data, it is possible to predict that one-third of a sample could be so characterized after 3.5 years. The photon absorption technique can be applied to the measurement of the rate of loss of mineral with aging with a precision that is sufficicient for certain types of clinical investigations."} {"id": "PMID:1270895", "title": "A capillary test for the control of heparin therapy.", "content": "The BaSon test (Baden, Sonnenfield) for the control of heparin therapy has been studied in capillary and venous blood of normal and heparinized children and the same reliability is found. The sensitivity to heparin and the reproducibility of the test have been observed in in invitro studies and the findings show that the sensitivity is excellent and the reproducibility is very good.", "contents": "A capillary test for the control of heparin therapy. The BaSon test (Baden, Sonnenfield) for the control of heparin therapy has been studied in capillary and venous blood of normal and heparinized children and the same reliability is found. The sensitivity to heparin and the reproducibility of the test have been observed in in invitro studies and the findings show that the sensitivity is excellent and the reproducibility is very good."} {"id": "PMID:1270896", "title": "A semiautomated micromethod for dextran in the presence of glucose.", "content": "A semiautomated method for microanalysis of dextran with anthrone reagent has been developed. The method utilizes the Technicon inulin manifold and other standard AutoAnalyzer equipment. Since the anthrone method is sensitive to plasma glucose, a glocuse oxidase method which eliminates glucose in samples to be analyzed for dextran has also been developed. When solutions containing 50 mg. per 100 ml. of dextran were compared to solutions containing 50 mg. per 100 ml. of dextran plus up to 200 mg. per 100 ml. glucose, no significant difference was observed. The coefficient of the anthrone-glucose oxidase method is 0.039, which is within the error of the AutoAnalyzer itself.", "contents": "A semiautomated micromethod for dextran in the presence of glucose. A semiautomated method for microanalysis of dextran with anthrone reagent has been developed. The method utilizes the Technicon inulin manifold and other standard AutoAnalyzer equipment. Since the anthrone method is sensitive to plasma glucose, a glocuse oxidase method which eliminates glucose in samples to be analyzed for dextran has also been developed. When solutions containing 50 mg. per 100 ml. of dextran were compared to solutions containing 50 mg. per 100 ml. of dextran plus up to 200 mg. per 100 ml. glucose, no significant difference was observed. The coefficient of the anthrone-glucose oxidase method is 0.039, which is within the error of the AutoAnalyzer itself."} {"id": "PMID:1270897", "title": "An enzymic method for the spectrophotometric determination of oxalic acid.", "content": "A simple method is described for the measurement of urinary oxalate. Oxalate decarboxylase is coupled with NAD+ requiring formate dehydrogenase and the result recorded spectrophotometrically. Accurate determination can be carried out either on urine or a citrate extract or urine. Using the citrate extract procedure, the urinary samples can be stored for at least 3 months without any effect on the oxalate content.", "contents": "An enzymic method for the spectrophotometric determination of oxalic acid. A simple method is described for the measurement of urinary oxalate. Oxalate decarboxylase is coupled with NAD+ requiring formate dehydrogenase and the result recorded spectrophotometrically. Accurate determination can be carried out either on urine or a citrate extract or urine. Using the citrate extract procedure, the urinary samples can be stored for at least 3 months without any effect on the oxalate content."} {"id": "PMID:1270906", "title": "Congenital aural and pre-auricular sinuses in the South African Bantu.", "content": "The incidence of ear pits was studied in the South African Bantu population. A short account of the anatomy, occurrence, inheritance, developmental origin, complications and treatment of this anomaly was given. Mention has been made of the clinical significance and the possible association between ear pits and other systemic and ear abnormalities, including deafness. There seems to be a higher incidence of other abnormalities in children born with sinuses. The blanket term 'pre-auricular fistula' should possibly be discarded in favour of auricular sinuses or ear pits.", "contents": "Congenital aural and pre-auricular sinuses in the South African Bantu. The incidence of ear pits was studied in the South African Bantu population. A short account of the anatomy, occurrence, inheritance, developmental origin, complications and treatment of this anomaly was given. Mention has been made of the clinical significance and the possible association between ear pits and other systemic and ear abnormalities, including deafness. There seems to be a higher incidence of other abnormalities in children born with sinuses. The blanket term 'pre-auricular fistula' should possibly be discarded in favour of auricular sinuses or ear pits."} {"id": "PMID:1270907", "title": "Audiological and haematological studies on the Todas of Nilgiris.", "content": "A detailed audiological study combined with certain haematological investigations which were never previously done was undertaken on Todas, a small vanishing tribe of Nilgiris, South India. Ten per cent of the Todas studied exhibited otosclerosis which, though lower than that of a previous study, is still a very high percentage when compared to the general population. The incidence of chronic suppurative otitis media in Todas is markedly low (1-6 per cent) and 13-3 per cent of Todas had sensorineural hearing loss. Evaluation of hearing thresholds at various frequencies in the different age groups did not show much variation from that of the general population. The incidence of presbyacusis is not found to be low as reported earlier. Blood pressure recordings did not show any age-related increase. The majority of Todas studied belonged to the blood group 'B' (63 per cent) and 16-6 per cent belonged to the 'AB' group, which is distinctly different from the distribution pattern seen in the general Indian population. There was no significant variation in the serum cholesterol level in Todas.", "contents": "Audiological and haematological studies on the Todas of Nilgiris. A detailed audiological study combined with certain haematological investigations which were never previously done was undertaken on Todas, a small vanishing tribe of Nilgiris, South India. Ten per cent of the Todas studied exhibited otosclerosis which, though lower than that of a previous study, is still a very high percentage when compared to the general population. The incidence of chronic suppurative otitis media in Todas is markedly low (1-6 per cent) and 13-3 per cent of Todas had sensorineural hearing loss. Evaluation of hearing thresholds at various frequencies in the different age groups did not show much variation from that of the general population. The incidence of presbyacusis is not found to be low as reported earlier. Blood pressure recordings did not show any age-related increase. The majority of Todas studied belonged to the blood group 'B' (63 per cent) and 16-6 per cent belonged to the 'AB' group, which is distinctly different from the distribution pattern seen in the general Indian population. There was no significant variation in the serum cholesterol level in Todas."} {"id": "PMID:1270908", "title": "Gunshot wounds to the head and neck.", "content": "The types of injury which occur as a result of the civil disturbances in the north of Ireland are described. Four cases of gunshot wounds to the head and neck are described, each of particular clinical interest. The recent literature on the subject is reviewed and the consensus of opinion appears to be that the safest policy is to explore all cases of penetrating wounds of the neck", "contents": "Gunshot wounds to the head and neck. The types of injury which occur as a result of the civil disturbances in the north of Ireland are described. Four cases of gunshot wounds to the head and neck are described, each of particular clinical interest. The recent literature on the subject is reviewed and the consensus of opinion appears to be that the safest policy is to explore all cases of penetrating wounds of the neck"} {"id": "PMID:1270909", "title": "Traumatic pneumocephalus.", "content": "A case is described of pneumocephalus involving both frontal lobes, following a frontoethmoidal fracture. It is noteworthy because it illustrates how extensive cerebral damage may be before it it detected. Intracerebral pneumocephalus occurs most commonly in fractures involving the frontal sinus or anterior ethmoidal/cribriform plate area. These fractures are not rare, and this potential complication should be in the minds of Ear, Nose and Throat surgeons who deal with trauma to the frontonasal region.", "contents": "Traumatic pneumocephalus. A case is described of pneumocephalus involving both frontal lobes, following a frontoethmoidal fracture. It is noteworthy because it illustrates how extensive cerebral damage may be before it it detected. Intracerebral pneumocephalus occurs most commonly in fractures involving the frontal sinus or anterior ethmoidal/cribriform plate area. These fractures are not rare, and this potential complication should be in the minds of Ear, Nose and Throat surgeons who deal with trauma to the frontonasal region."} {"id": "PMID:1270910", "title": "Oxygen tension and surface temperature of the endonasal tissues in the goat. Preliminary report.", "content": "Measurement of the PO2 in the mucosal cells and at various depths of the lamina propria lining the nasal cavity in five male goats using Silver's special microelectrodes, revealed relative hypoxia in the anterodorsal part of the nasal septum and tips of naso- and maxilloturbinals. In these sites PO2 values varied between 55-65 at the surface and 30-35 in the superficial subepithlial layer while elsewhere in the nose, lip and tongue, PO2 values of 85-90 were obtained. Temperature measurements with the thermistor in two goats yielded readings of 34-34-5 degrees C. in the hypoxic areas against 36-37 degrees C. in the posterior parts, the roof and floor of the nasal cavity. However, the oxygen tension diminished steadily in all areas as the microneedle electrode approached the chondro-osteal tissues but PO2 values of 0-10 in the perichondrium. The significance of these findings in the predilective localization of granulomata and various forms of vasculitis in the anterior endonasal tissues has been discussed.", "contents": "Oxygen tension and surface temperature of the endonasal tissues in the goat. Preliminary report. Measurement of the PO2 in the mucosal cells and at various depths of the lamina propria lining the nasal cavity in five male goats using Silver's special microelectrodes, revealed relative hypoxia in the anterodorsal part of the nasal septum and tips of naso- and maxilloturbinals. In these sites PO2 values varied between 55-65 at the surface and 30-35 in the superficial subepithlial layer while elsewhere in the nose, lip and tongue, PO2 values of 85-90 were obtained. Temperature measurements with the thermistor in two goats yielded readings of 34-34-5 degrees C. in the hypoxic areas against 36-37 degrees C. in the posterior parts, the roof and floor of the nasal cavity. However, the oxygen tension diminished steadily in all areas as the microneedle electrode approached the chondro-osteal tissues but PO2 values of 0-10 in the perichondrium. The significance of these findings in the predilective localization of granulomata and various forms of vasculitis in the anterior endonasal tissues has been discussed."} {"id": "PMID:1270911", "title": "Malignant lymphoma presenting as a parotid mass.", "content": "Three cases of maglignant lymphoma presenting as a parotid mass have been presented. Head and neck surgeons should be aware of this condition both as a possible variant of lymphoma presenting in the head and neck region, and also as a part of the differential diagnosis of parotid gland enlargement. Early diagnosis is essential in these cases, as this has a beneficial effect on both the prognosis and management of these patients. The histopathology and staging of these tumors has been discussed with regards to the prognosis and management, and the difficulty of making the diagnosis and the chances to improve this are also discussed.", "contents": "Malignant lymphoma presenting as a parotid mass. Three cases of maglignant lymphoma presenting as a parotid mass have been presented. Head and neck surgeons should be aware of this condition both as a possible variant of lymphoma presenting in the head and neck region, and also as a part of the differential diagnosis of parotid gland enlargement. Early diagnosis is essential in these cases, as this has a beneficial effect on both the prognosis and management of these patients. The histopathology and staging of these tumors has been discussed with regards to the prognosis and management, and the difficulty of making the diagnosis and the chances to improve this are also discussed."} {"id": "PMID:1270912", "title": "Myiasis in otorhinolaryngology with entomological aspects.", "content": "Maggot infestation in a series of 100 cases pertaining to the E.N.T. domain is reported. The Entomological aspects were studied in 20 cases. The clinical features of myiasis have been described. This disease commonly occurs in diseased nasal and ear cavities which allow maggots to grow. The use of maggot oil drops and irrigation with normal saline provides an effective treatment. Prevention of maggot infestation is stressed.", "contents": "Myiasis in otorhinolaryngology with entomological aspects. Maggot infestation in a series of 100 cases pertaining to the E.N.T. domain is reported. The Entomological aspects were studied in 20 cases. The clinical features of myiasis have been described. This disease commonly occurs in diseased nasal and ear cavities which allow maggots to grow. The use of maggot oil drops and irrigation with normal saline provides an effective treatment. Prevention of maggot infestation is stressed."} {"id": "PMID:1270914", "title": "The oto-palato-digital syndrome.", "content": "A boy aged ten years with oto-palato-digital syndrome is discussed. Because of severe conductive hearing loss tympanotomy was performed and abnormal poorly mobile ossicles were found. Stapedectomy was performed without improvement of hearing.", "contents": "The oto-palato-digital syndrome. A boy aged ten years with oto-palato-digital syndrome is discussed. Because of severe conductive hearing loss tympanotomy was performed and abnormal poorly mobile ossicles were found. Stapedectomy was performed without improvement of hearing."} {"id": "PMID:1270915", "title": "Wound infection following laryngectomy. The effect of topical ampicillin and carbenicillin.", "content": "A study of twenty-two consecutive laryngectomies performed in one unit is reported. In eleven controls, seven (67%) developed a wound infection. In eleven patients, IG of Ampicillin and IG of Carbenicillin were used topically, and three (18%) developed a wound infection (P less than 0-04). Studies of the bacterial flora at the time of operation suggest that the major source of wound contamination is colonization of the upper gastrointestinal and respiratory tract. The ease with which a small innoculum of pathogens produces wound infection in these patients is discussed, and it is suggested that the underlying defect is depression of host cellular immunity resulting in failure of bacterial destruction by activated macrophages.", "contents": "Wound infection following laryngectomy. The effect of topical ampicillin and carbenicillin. A study of twenty-two consecutive laryngectomies performed in one unit is reported. In eleven controls, seven (67%) developed a wound infection. In eleven patients, IG of Ampicillin and IG of Carbenicillin were used topically, and three (18%) developed a wound infection (P less than 0-04). Studies of the bacterial flora at the time of operation suggest that the major source of wound contamination is colonization of the upper gastrointestinal and respiratory tract. The ease with which a small innoculum of pathogens produces wound infection in these patients is discussed, and it is suggested that the underlying defect is depression of host cellular immunity resulting in failure of bacterial destruction by activated macrophages."} {"id": "PMID:1270916", "title": "Deep vein thrombosis in ear, nose and throat surgery.", "content": "I. One hundred and three patients undergoing head and neck or ear operations were screened for deep vein thrombosis using I125 labelled fibrinogen. 2. No thrombosis was detected in thirty-five patients undergoing ear operations. 3. Nine (16%) of fifty-six patients who underwent head and neck operations subsequently developed deep vein thrombosis. In a further twelve patients undergoing head and neck operations the ankle was used as a drip site and seven of these patients developed thrombosis in that leg.", "contents": "Deep vein thrombosis in ear, nose and throat surgery. I. One hundred and three patients undergoing head and neck or ear operations were screened for deep vein thrombosis using I125 labelled fibrinogen. 2. No thrombosis was detected in thirty-five patients undergoing ear operations. 3. Nine (16%) of fifty-six patients who underwent head and neck operations subsequently developed deep vein thrombosis. In a further twelve patients undergoing head and neck operations the ankle was used as a drip site and seven of these patients developed thrombosis in that leg."} {"id": "PMID:1270917", "title": "Cochlear implants.", "content": "All presently devised single channel devices generate a primitive sensation of hearing by the mechanism of 'periodicity pitch'. No 'place pitch' encoding is possible. Although some enhancement of communicative skills with lip reading results, unaided speech discrimination is not possible. Definite psychological advantages for the totally deaf have been observed with these simple devices. Multiple segments of auditory nerve must be stimulated in a manner which will simulate the complex patterns of neural activity necessary for speech discrimination. Electrode optimization and the pathophysiological consequences of electrical stimulation of the auditory nerve can best be determined in animals. The perceptual consequences of electrical stimulation of the auditory nerve, however, can best be determined in man. How much we will have to innovate the methods of aural rehabilitation will depend upon how well we can generate perceptual speech patterns by electrical excitation of the auditory nerve.", "contents": "Cochlear implants. All presently devised single channel devices generate a primitive sensation of hearing by the mechanism of 'periodicity pitch'. No 'place pitch' encoding is possible. Although some enhancement of communicative skills with lip reading results, unaided speech discrimination is not possible. Definite psychological advantages for the totally deaf have been observed with these simple devices. Multiple segments of auditory nerve must be stimulated in a manner which will simulate the complex patterns of neural activity necessary for speech discrimination. Electrode optimization and the pathophysiological consequences of electrical stimulation of the auditory nerve can best be determined in animals. The perceptual consequences of electrical stimulation of the auditory nerve, however, can best be determined in man. How much we will have to innovate the methods of aural rehabilitation will depend upon how well we can generate perceptual speech patterns by electrical excitation of the auditory nerve."} {"id": "PMID:1270918", "title": "The cochlear histopathology of chronic intracochlear implantation.", "content": "A fundamental question regarding the feasibility of artificial electrical stimulation of auditory nerve in cases of sensory deafness is the fate of that nerve after electrode implantation. The results of chronic scala tympani electrode implantation in normal and neomycin-deafened cats indicate that the vast majority of primary auditory neurons will survive the initial surgical implantation and the long-term interface with the molded silastic electrode for periods of at least 30 months (the longest normal-implant survivors). While there is histologic evidence that some neurons are lost in the basal coil, especially in neomycin-deafened animals, the majority of spiral ganglion cells and their radial fibres survived neomycin administration and surgical implantation even in this region. The implantation of electrodes in neomycin-deafened cats did not result in heavy neuronal degeneration. Indeed, there was little apparent difference in nerve survival between the implanted and unimplanted ears of the neomycin animals for periods up to five months (the longest neomycin implant survivor). Traumatic electrode insertion with injury to the boney covering of the modiolus or disruption of the basilar membrane resulted in extensive nerve loss in the traumatized region. When carefully inserted by an experienced otologist, the molded-silastic scala tympani electrode permitted discrete differential stimulation of restricted segments of auditory nerve and produced little or no neural degeneration.", "contents": "The cochlear histopathology of chronic intracochlear implantation. A fundamental question regarding the feasibility of artificial electrical stimulation of auditory nerve in cases of sensory deafness is the fate of that nerve after electrode implantation. The results of chronic scala tympani electrode implantation in normal and neomycin-deafened cats indicate that the vast majority of primary auditory neurons will survive the initial surgical implantation and the long-term interface with the molded silastic electrode for periods of at least 30 months (the longest normal-implant survivors). While there is histologic evidence that some neurons are lost in the basal coil, especially in neomycin-deafened animals, the majority of spiral ganglion cells and their radial fibres survived neomycin administration and surgical implantation even in this region. The implantation of electrodes in neomycin-deafened cats did not result in heavy neuronal degeneration. Indeed, there was little apparent difference in nerve survival between the implanted and unimplanted ears of the neomycin animals for periods up to five months (the longest neomycin implant survivor). Traumatic electrode insertion with injury to the boney covering of the modiolus or disruption of the basilar membrane resulted in extensive nerve loss in the traumatized region. When carefully inserted by an experienced otologist, the molded-silastic scala tympani electrode permitted discrete differential stimulation of restricted segments of auditory nerve and produced little or no neural degeneration."} {"id": "PMID:1270920", "title": "Secretory otitis. Histopathology and goblet-cell density in the Eustachian tube and middle ear in children.", "content": "The histological changes in the middle ear of four children with incipient or mild chronic secretory otitis are described. They consist in vascular dilatation and proliferation, round-cell infiltration, epithelial metaplasia into pseudostratified, columnar, ciliated epithelium posteriorly in the middle ear, formation of abnormal mucous tubular glands, and an increase in goblet-cell density in the osseous tube and middle ear. The causes of these changes were presumably long-lasting tubal occlusion due to a permanent nasogastric tube and protracted catarrhal diseases. The density of goblet cells was determined in various parts of the Eustachian tube and middle ear. The findings were analysed statistically and compared with the density in prematures and newborns, normal children, and normal adults. In the tympanic orifice and in the osseous Eustachian tube the goblet-cell density was greatly increased, whereas the increase in the middle ear varied individually, but was in conformity with the other findings. These cases illustrate that the histopathological changes in the middle-ear mucosa in secretory otitis must be regarded not only from a qualitative, but certainly also from a quantitative point of view.", "contents": "Secretory otitis. Histopathology and goblet-cell density in the Eustachian tube and middle ear in children. The histological changes in the middle ear of four children with incipient or mild chronic secretory otitis are described. They consist in vascular dilatation and proliferation, round-cell infiltration, epithelial metaplasia into pseudostratified, columnar, ciliated epithelium posteriorly in the middle ear, formation of abnormal mucous tubular glands, and an increase in goblet-cell density in the osseous tube and middle ear. The causes of these changes were presumably long-lasting tubal occlusion due to a permanent nasogastric tube and protracted catarrhal diseases. The density of goblet cells was determined in various parts of the Eustachian tube and middle ear. The findings were analysed statistically and compared with the density in prematures and newborns, normal children, and normal adults. In the tympanic orifice and in the osseous Eustachian tube the goblet-cell density was greatly increased, whereas the increase in the middle ear varied individually, but was in conformity with the other findings. These cases illustrate that the histopathological changes in the middle-ear mucosa in secretory otitis must be regarded not only from a qualitative, but certainly also from a quantitative point of view."} {"id": "PMID:1270923", "title": "The aetiology of otitis externa--a new concept.", "content": "This paper reports the results of middle ear pressure measurements on 33 patients with recurrent otitis externa and compares the results with those of 21 normal subjects. The maximum negative pressure in the control group was -50 mm. of water, while 17 patients (52%) with recurrent otitis externa recorded measurements of -100 mm. of water or more. It is postulated that chronic Eustachian tube dysfunction may interfere with the normal migration of epithelium from the tympanic membrane along the external auditory meatus leading to irritation and chronic infection. The treatment in these cases should be directed at the underlying cause of the Eustachian tube dysfunction.", "contents": "The aetiology of otitis externa--a new concept. This paper reports the results of middle ear pressure measurements on 33 patients with recurrent otitis externa and compares the results with those of 21 normal subjects. The maximum negative pressure in the control group was -50 mm. of water, while 17 patients (52%) with recurrent otitis externa recorded measurements of -100 mm. of water or more. It is postulated that chronic Eustachian tube dysfunction may interfere with the normal migration of epithelium from the tympanic membrane along the external auditory meatus leading to irritation and chronic infection. The treatment in these cases should be directed at the underlying cause of the Eustachian tube dysfunction."} {"id": "PMID:1270929", "title": "Analysis of bile acids in conventional and germfree rats.", "content": "The well-known bile acid analysis technique used by us and others (Grundy, Ahrens, and Miettinen. 1965. J. Lipid Res. 6:397-410) does not allow for the detection of hyodeoxycholic acid, a product of quantitative importance in rodent feces. Using updated methodology, it was established that hyodeoxycholic acid and omega-muricholic acid, both apparent conversion products of beta-muricholic acid, occur in apppreciable amounts in intestinal contents and feces of conventional Wistar type Lobund rats. In conventional rats, these bile acids comprise about 50% of fecal bile acids; they are not found in intestinal contents or feces of germfree rats. Others have demonstrated that hyodeoxycholic acid if formed by combined action of gut flora and liver. A new method for the separation of conjugated and free bile acids in biological samples was developed. Results with this method confirmed the total conjugation of bile acids in the germfree rat, and the almost total deconjugation that takes place in the cecum of the conventional rat.", "contents": "Analysis of bile acids in conventional and germfree rats. The well-known bile acid analysis technique used by us and others (Grundy, Ahrens, and Miettinen. 1965. J. Lipid Res. 6:397-410) does not allow for the detection of hyodeoxycholic acid, a product of quantitative importance in rodent feces. Using updated methodology, it was established that hyodeoxycholic acid and omega-muricholic acid, both apparent conversion products of beta-muricholic acid, occur in apppreciable amounts in intestinal contents and feces of conventional Wistar type Lobund rats. In conventional rats, these bile acids comprise about 50% of fecal bile acids; they are not found in intestinal contents or feces of germfree rats. Others have demonstrated that hyodeoxycholic acid if formed by combined action of gut flora and liver. A new method for the separation of conjugated and free bile acids in biological samples was developed. Results with this method confirmed the total conjugation of bile acids in the germfree rat, and the almost total deconjugation that takes place in the cecum of the conventional rat."} {"id": "PMID:1270930", "title": "Preparation of laurylsarcosyltaurine: a surface active constituent of crab gastric juice.", "content": "The conditions for the preparation of laurylsarcosyltaurine from lauric acid and sarcosyltaurine, a crystalline dipeptide, are described. The preparation of sarcosyltaurine from the reaction of taurine and the mixed anhydride of benzyloxycarbonylsarcosine and isobutyl chloroformate is also described.", "contents": "Preparation of laurylsarcosyltaurine: a surface active constituent of crab gastric juice. The conditions for the preparation of laurylsarcosyltaurine from lauric acid and sarcosyltaurine, a crystalline dipeptide, are described. The preparation of sarcosyltaurine from the reaction of taurine and the mixed anhydride of benzyloxycarbonylsarcosine and isobutyl chloroformate is also described."} {"id": "PMID:1270931", "title": "Halofenate and clofibrate: mechanism of hypotriglyceridemic action in the rat.", "content": "Rats fed a fat-free diet containing no drug, 0.02% or 0.10% halofenate, or 0.25% clofibrate for 14 days were injected intravenously with equivalent amounts of either [2-3H]glycerol or [1(3)-3H]glycerol. Blood samples were collected at times up to 150 min after injection and serum triglycerides were isolated and assayed for radioactivity. Kinetic analysis of the serum appearance and clearance curves of 3H-labeled triglyceride permits estimation of serum total 3H-labeled triglyceride formation and triglyceride fractional turnover rates. The total amounts of 3H-labeled triglyceride formed from [2-3H] or from [1(3)-3H] glycerol in control-fed animals were very similar. Over 95% of the serum 3H-labeled triglyceride formed from either substrate circulated in a rapidly turning-over triglyceride pool (t1/2 = 8 min). Treatment with 0.10% halofenate or 0.25% clofibrate decreased labeling of serum triglycerides by 75-80% without increasing serum 3H-labeled triglyceride fractional turnover rates. Furthermore, both drugs decreased incorporation in vivo of 14C from [U-14C]glycerol into hepatic but not intestinal triglycerides without significantly decreasing incorporation of 14C into total phospholipids of either tissue. From these observations we suggest that, in the intact normal rat, sustained reduction of serum triglyceride levels produced by treatment with halofenate or clofibrate is due to inhibition of hepatic triglyceride formation.", "contents": "Halofenate and clofibrate: mechanism of hypotriglyceridemic action in the rat. Rats fed a fat-free diet containing no drug, 0.02% or 0.10% halofenate, or 0.25% clofibrate for 14 days were injected intravenously with equivalent amounts of either [2-3H]glycerol or [1(3)-3H]glycerol. Blood samples were collected at times up to 150 min after injection and serum triglycerides were isolated and assayed for radioactivity. Kinetic analysis of the serum appearance and clearance curves of 3H-labeled triglyceride permits estimation of serum total 3H-labeled triglyceride formation and triglyceride fractional turnover rates. The total amounts of 3H-labeled triglyceride formed from [2-3H] or from [1(3)-3H] glycerol in control-fed animals were very similar. Over 95% of the serum 3H-labeled triglyceride formed from either substrate circulated in a rapidly turning-over triglyceride pool (t1/2 = 8 min). Treatment with 0.10% halofenate or 0.25% clofibrate decreased labeling of serum triglycerides by 75-80% without increasing serum 3H-labeled triglyceride fractional turnover rates. Furthermore, both drugs decreased incorporation in vivo of 14C from [U-14C]glycerol into hepatic but not intestinal triglycerides without significantly decreasing incorporation of 14C into total phospholipids of either tissue. From these observations we suggest that, in the intact normal rat, sustained reduction of serum triglyceride levels produced by treatment with halofenate or clofibrate is due to inhibition of hepatic triglyceride formation."} {"id": "PMID:1270932", "title": "Characterization of myelin of chick sciatic nerve during development.", "content": "Myelin was isolated from the sciatic nerves of chicks of ages 18-day embryonic, 1-day, 4-day, 7-day post-hatch, and adult to study developmental changes in lipid composition of this structure. The yield of myelin increased throughout the early stages of development and the preparations were of high purity. Although the lipid content of the myelin did not change, significant changes took place in lipid composition during development. The most significant changes were a relative increase in cerebrosides, phosphatidalethanolamine and long-chain fatty acids of cerebrosides, and a relative decrease in the content of phosphatidylserine and phosphatidylethanolamine. A second fraction (\"lower band\") was obtained during the isolation procedure. This \"lower band\" was present at all developmental stages and layered consistently at the interface of 1.2 and 0.8 M sucrose on a discontinuous gradient. The quantity of this fraction did not change during development and it differed from myelin in electron microscopic appearance. Its lipid composition, which did not change, resembled that of 18-day embryonic myelin in its high phospholipid:cholesterol ratio and low galactolipid content. The enzyme, 2':3'-cyclic-nucleosidemonophosphate phosphodiesterase was found to be present in both the myelin and \"lower band\" fractions; however there was no enrichment of this enzyme in purified myelin.", "contents": "Characterization of myelin of chick sciatic nerve during development. Myelin was isolated from the sciatic nerves of chicks of ages 18-day embryonic, 1-day, 4-day, 7-day post-hatch, and adult to study developmental changes in lipid composition of this structure. The yield of myelin increased throughout the early stages of development and the preparations were of high purity. Although the lipid content of the myelin did not change, significant changes took place in lipid composition during development. The most significant changes were a relative increase in cerebrosides, phosphatidalethanolamine and long-chain fatty acids of cerebrosides, and a relative decrease in the content of phosphatidylserine and phosphatidylethanolamine. A second fraction (\"lower band\") was obtained during the isolation procedure. This \"lower band\" was present at all developmental stages and layered consistently at the interface of 1.2 and 0.8 M sucrose on a discontinuous gradient. The quantity of this fraction did not change during development and it differed from myelin in electron microscopic appearance. Its lipid composition, which did not change, resembled that of 18-day embryonic myelin in its high phospholipid:cholesterol ratio and low galactolipid content. The enzyme, 2':3'-cyclic-nucleosidemonophosphate phosphodiesterase was found to be present in both the myelin and \"lower band\" fractions; however there was no enrichment of this enzyme in purified myelin."} {"id": "PMID:1270933", "title": "An enzymatic method for the determination of the initial rate of cholesterol esterification in human plasma.", "content": "A method is described for the determination of the initial rate of cholesterol esterification in human plasma, based on the enzymatic determination of free cholesterol in the plasma before and after incubation at 37 degrees C. The cholesterol esterification rate was linear up to 40 minutes. In 18 normal male and 10 normal female subjects the cholesterol esterification rate was 91 +/- 15 (mean +/- SD) and 62 +/- 12 nmoles/hr/ml of plasma, respectively.", "contents": "An enzymatic method for the determination of the initial rate of cholesterol esterification in human plasma. A method is described for the determination of the initial rate of cholesterol esterification in human plasma, based on the enzymatic determination of free cholesterol in the plasma before and after incubation at 37 degrees C. The cholesterol esterification rate was linear up to 40 minutes. In 18 normal male and 10 normal female subjects the cholesterol esterification rate was 91 +/- 15 (mean +/- SD) and 62 +/- 12 nmoles/hr/ml of plasma, respectively."} {"id": "PMID:1270934", "title": "Automated glass capillary gas-liquid chromatography of fatty acid methyl esters with reference to cis and trans isomers.", "content": "The availability of an excellent separation method for fatty acid methyl esters, including separation of cis and trans isomers and of isomers that differ only in the position of double bonds, has become more and more important. The present glass capillary chromatography system combines high separation power with high precision and easy handling. Moreover, the system is completely automated and therefore provides a time saving method. As compared to a conventional packed column, the glass capillary column provides about one hundred fold more theoretical plates (227,000), as well as narrower peaks, thus giving rise to less error when integrating with electronic integrators. The reproducibility for relative retention time is better with the capillary column (0.26%) and reproducibility of the weight percent values is at least similar to that of the packed column (1.53%). When handling only small sample amounts the capillary provides better values because of its low capacity. This powerful system should open up new possibilities in the field of fatty acid investigation.", "contents": "Automated glass capillary gas-liquid chromatography of fatty acid methyl esters with reference to cis and trans isomers. The availability of an excellent separation method for fatty acid methyl esters, including separation of cis and trans isomers and of isomers that differ only in the position of double bonds, has become more and more important. The present glass capillary chromatography system combines high separation power with high precision and easy handling. Moreover, the system is completely automated and therefore provides a time saving method. As compared to a conventional packed column, the glass capillary column provides about one hundred fold more theoretical plates (227,000), as well as narrower peaks, thus giving rise to less error when integrating with electronic integrators. The reproducibility for relative retention time is better with the capillary column (0.26%) and reproducibility of the weight percent values is at least similar to that of the packed column (1.53%). When handling only small sample amounts the capillary provides better values because of its low capacity. This powerful system should open up new possibilities in the field of fatty acid investigation."} {"id": "PMID:1270935", "title": "Human fat cell sizing--a quick, simple method.", "content": "Two methods were used to determine the mean cell diameters of 37 samples of human adipose tissue, obtained by open or needle biopsy. Method I was the sizing of cells in cell suspensions and Method II was a quick, simple method of sizing cells from fixed sections. The agreement between the two methods was good (r = 0.93, P = less than 0.001). The results using Method II were slightly lower than those using Method I, and a correction factor is suggested. Method II has several advantages over Method I and we propose that it is a suitable method for sizing cells when a quick method with a permanent record is required.", "contents": "Human fat cell sizing--a quick, simple method. Two methods were used to determine the mean cell diameters of 37 samples of human adipose tissue, obtained by open or needle biopsy. Method I was the sizing of cells in cell suspensions and Method II was a quick, simple method of sizing cells from fixed sections. The agreement between the two methods was good (r = 0.93, P = less than 0.001). The results using Method II were slightly lower than those using Method I, and a correction factor is suggested. Method II has several advantages over Method I and we propose that it is a suitable method for sizing cells when a quick method with a permanent record is required."} {"id": "PMID:1270936", "title": "Sterol balance in hyperlipidemic patients after dietary exchange of carbohydrate for fat.", "content": "Dextrose was exchanged isocalorically for polyunsaturated fat in the liquid formula diets of 10 hyperlipidemic patients maintained under metabolic steady state conditions. Carbohydrate caused an increase of plasma triglycerides in all 10; plasma cholesterol rose in 7, and 6 of these 7 failed to show any increase in total fecal excretion of cholesterol. In contrast, fecal steroid excretion increased significantly in the three patients who maintained an unchanged or lower plasma cholesterol on the high-carbohydrate diet. Squalene, an obligatory precursor in the biosynthesis of cholesterol, rose in the plasma during carbohydrate feeding in 6 out of 6 patients studied. After a single intravenous infusion of radioactive cholesterol, plasma and feces were analyzed for specific activity over at least a four-month period. Plasma and fecal neutral sterol specific activity were essentially equivalent at all times in all patients, regardless of feeding regimen. On institution of carbohydrate feeding, the slope of cholesterol specific activity flattened for those seven patients who had a rise in plasma cholesterol concentration. There was no change in slope for the two patients with fixed plasma cholesterol levels nor for the one patient with a decreased plasma cholesterol on the high-carbohydrate diet. These experiments demonstrate a divergent response between plasma cholesterol concentration and cholesterol excretion. To establish causal relationship between the two (i.e., plasma cholesterol increases because excretion does not increase) will require further research. The flattening of specific activity die-away curves with rising cholesterol concentrations is best explained by mobilization of slowly turning-over tissue cholesterol into plasma. A subsequent decrease in cholesterol synthesis would also add to the slower decline of plasma cholesterol specific activity.", "contents": "Sterol balance in hyperlipidemic patients after dietary exchange of carbohydrate for fat. Dextrose was exchanged isocalorically for polyunsaturated fat in the liquid formula diets of 10 hyperlipidemic patients maintained under metabolic steady state conditions. Carbohydrate caused an increase of plasma triglycerides in all 10; plasma cholesterol rose in 7, and 6 of these 7 failed to show any increase in total fecal excretion of cholesterol. In contrast, fecal steroid excretion increased significantly in the three patients who maintained an unchanged or lower plasma cholesterol on the high-carbohydrate diet. Squalene, an obligatory precursor in the biosynthesis of cholesterol, rose in the plasma during carbohydrate feeding in 6 out of 6 patients studied. After a single intravenous infusion of radioactive cholesterol, plasma and feces were analyzed for specific activity over at least a four-month period. Plasma and fecal neutral sterol specific activity were essentially equivalent at all times in all patients, regardless of feeding regimen. On institution of carbohydrate feeding, the slope of cholesterol specific activity flattened for those seven patients who had a rise in plasma cholesterol concentration. There was no change in slope for the two patients with fixed plasma cholesterol levels nor for the one patient with a decreased plasma cholesterol on the high-carbohydrate diet. These experiments demonstrate a divergent response between plasma cholesterol concentration and cholesterol excretion. To establish causal relationship between the two (i.e., plasma cholesterol increases because excretion does not increase) will require further research. The flattening of specific activity die-away curves with rising cholesterol concentrations is best explained by mobilization of slowly turning-over tissue cholesterol into plasma. A subsequent decrease in cholesterol synthesis would also add to the slower decline of plasma cholesterol specific activity."} {"id": "PMID:1270947", "title": "Oestriol, oestradiol-17beta and the proliferation and death of uterine cells.", "content": "It has been suggested that oestriol protects against breast cancer, because in some experiments on uterine growth it is only weakly active, and partially inhibits the effects of oestradiol-17beta. When its effects are measured 24 h after a single injection, oestriol behaves as a typical impeded oestrogen with low potency and a flat dose-response line. This does not result from failure to stimulate certain critical stages of growth but from failure to sustain the products of growth. We found that oestriol induced all phases of uterine growth including DNA synthesis and cell division. It was as effective as oestradiol in stimulating early increases in protein synthesis and uterine weight, and half as effective in stimulating epithelial cells to replicate DNA and divide. However, epithelial cell numbers did not increase after a single injection of oestriol because cell death rate increased at the same time as mitotic rate, apparently as a result of the more rapid loss of oestriol from the uterus. Repeated injections of oestriol prevented premature cell death and produced as much uterine hypertrophy and hyperplasia as oestradiol-17beta. These results support the thesis that the oestrogenic potency of a substance is largely determined by the duration of its occupation of receptors. Thus in situations of continuous production, (e.g. pregnancy) oestriol would be as active as oestradiol and unlikely to exert any significant 'buffering' or protective action. The findings are also discussed in relation to a new model for the regulation of cell proliferation.", "contents": "Oestriol, oestradiol-17beta and the proliferation and death of uterine cells. It has been suggested that oestriol protects against breast cancer, because in some experiments on uterine growth it is only weakly active, and partially inhibits the effects of oestradiol-17beta. When its effects are measured 24 h after a single injection, oestriol behaves as a typical impeded oestrogen with low potency and a flat dose-response line. This does not result from failure to stimulate certain critical stages of growth but from failure to sustain the products of growth. We found that oestriol induced all phases of uterine growth including DNA synthesis and cell division. It was as effective as oestradiol in stimulating early increases in protein synthesis and uterine weight, and half as effective in stimulating epithelial cells to replicate DNA and divide. However, epithelial cell numbers did not increase after a single injection of oestriol because cell death rate increased at the same time as mitotic rate, apparently as a result of the more rapid loss of oestriol from the uterus. Repeated injections of oestriol prevented premature cell death and produced as much uterine hypertrophy and hyperplasia as oestradiol-17beta. These results support the thesis that the oestrogenic potency of a substance is largely determined by the duration of its occupation of receptors. Thus in situations of continuous production, (e.g. pregnancy) oestriol would be as active as oestradiol and unlikely to exert any significant 'buffering' or protective action. The findings are also discussed in relation to a new model for the regulation of cell proliferation."} {"id": "PMID:1270948", "title": "Effects of new multi-site hormone blockers on the fertility of male rats.", "content": "The effects on the fertility of adult male rats of six new synthetic steroids: I, 3-cyano-5alpha-androst-1-en-17-one; II, the 17beta-acetate form of I; III, 17beta-hydroxy-5beta-cyano-androstan-3-one; IV, 6-methylpregnenolone; V, 17beta-hydroxy-17alpha-ethynyl-5beta-cyano-19-norandrostan-3-one; and VI, 19-norspiroxenone (oestr-4-en-3-one-spiro-17alpha-2'-[tetrahydrofuran]) have been tested. After 6 weeks of treatment with daily doses of 5 mg (I, II, III), 15 mg (IV) or 10 mg (V, VI) only steroid VI blocked the completion of spermatogenesis and reduced the number of foetuses sired in at least five females/male. Steroid VI also diminished seminal vesicular, prostatic, testicular and epididymal weights. It inhibited the testicular enzymes, 3beta-hydroxysteroid dehydrogenase-delta4-5-3-oxosteroid isomerase system, 17alpha-hydroxylase, and C17-20 lyase markedly, but did not affect the adrenal dehydrogenase-isomerase system. It depressed, strikingly, testicular and serum levels of testosterone and 5alpha-dihydrotestosterone and reduced pituitary and serum levels of FSH and LH. Although marked depression of target organ weights also occurred with steroids II, IV and V, and reduction of androgen levels and LH in the circulation with III, IV and V, only VI was a potent blocker of male fertility with the exception of a slight block of the siring of viable foetuses by steroids IV and V. The major difference in site of action of steroid VI from the others was the depression of pituitary and serum levels of FSH along with a marked diminution of testicular content of both testosterone and 5alpha-dihydrotestosterone. 19-Norspiroxenone in the rat is a potent anti-oestrogen without inherent oestrogenicity and is anti-uterotrophic. Thus, VI may affect male fertility by virtue of its potent anti-oestrogenic action in the hypothalamus or testis.", "contents": "Effects of new multi-site hormone blockers on the fertility of male rats. The effects on the fertility of adult male rats of six new synthetic steroids: I, 3-cyano-5alpha-androst-1-en-17-one; II, the 17beta-acetate form of I; III, 17beta-hydroxy-5beta-cyano-androstan-3-one; IV, 6-methylpregnenolone; V, 17beta-hydroxy-17alpha-ethynyl-5beta-cyano-19-norandrostan-3-one; and VI, 19-norspiroxenone (oestr-4-en-3-one-spiro-17alpha-2'-[tetrahydrofuran]) have been tested. After 6 weeks of treatment with daily doses of 5 mg (I, II, III), 15 mg (IV) or 10 mg (V, VI) only steroid VI blocked the completion of spermatogenesis and reduced the number of foetuses sired in at least five females/male. Steroid VI also diminished seminal vesicular, prostatic, testicular and epididymal weights. It inhibited the testicular enzymes, 3beta-hydroxysteroid dehydrogenase-delta4-5-3-oxosteroid isomerase system, 17alpha-hydroxylase, and C17-20 lyase markedly, but did not affect the adrenal dehydrogenase-isomerase system. It depressed, strikingly, testicular and serum levels of testosterone and 5alpha-dihydrotestosterone and reduced pituitary and serum levels of FSH and LH. Although marked depression of target organ weights also occurred with steroids II, IV and V, and reduction of androgen levels and LH in the circulation with III, IV and V, only VI was a potent blocker of male fertility with the exception of a slight block of the siring of viable foetuses by steroids IV and V. The major difference in site of action of steroid VI from the others was the depression of pituitary and serum levels of FSH along with a marked diminution of testicular content of both testosterone and 5alpha-dihydrotestosterone. 19-Norspiroxenone in the rat is a potent anti-oestrogen without inherent oestrogenicity and is anti-uterotrophic. Thus, VI may affect male fertility by virtue of its potent anti-oestrogenic action in the hypothalamus or testis."} {"id": "PMID:1270949", "title": "Plasma follicle-stimulating hormone during photoperiodically induced sexual maturation in male Japanese quail.", "content": "Follicle-stimulating hormone (FSH) was measured in Japanese quail using a heterologous radioimmunoassay, the specificty of which was confirmed by its cross-reactions with purified chicken FSH and luteinizing hormone (LH). Plasma concentrations of FSH, LH and testosterone were determined in quail during the testicular growth and sexual maturation which follows their transfer from short to long daylengths. All three hormones could be detected in short-day birds but their concentrations were greatly increased following photostimulation. Plasma FSH increased 12-fold during the first 9 long days, remained at this level for a week, and then declined steadily so that by the time the birds were sexually mature the level of FSH had decreased to one-third of the maximum level. LH reached a high level (five times the short day level) after 4 long days. Thereafter two patterns of LH secretion could be distinguished. In one experiment the high level of LH was maintained unchanged throughout sexual maturation while in another experiment LH secretion decreased significantly between days 11 and 28 of photostimulation. A strong correlation existed between testicular growth and the plasma FSH concentration. It was maximal during the phase of rapid testicular growth and decreased as spermiogenesis began. The pituitary FSH content increased during photostimulation. Castration caused a 20-fold rise in plasma FSH compared with that in intact quail. The change in LH concentration after castration was about eightfold. The changes in hormone secretion were strikingly similar to those found during sexual development and puberty in the rat.", "contents": "Plasma follicle-stimulating hormone during photoperiodically induced sexual maturation in male Japanese quail. Follicle-stimulating hormone (FSH) was measured in Japanese quail using a heterologous radioimmunoassay, the specificty of which was confirmed by its cross-reactions with purified chicken FSH and luteinizing hormone (LH). Plasma concentrations of FSH, LH and testosterone were determined in quail during the testicular growth and sexual maturation which follows their transfer from short to long daylengths. All three hormones could be detected in short-day birds but their concentrations were greatly increased following photostimulation. Plasma FSH increased 12-fold during the first 9 long days, remained at this level for a week, and then declined steadily so that by the time the birds were sexually mature the level of FSH had decreased to one-third of the maximum level. LH reached a high level (five times the short day level) after 4 long days. Thereafter two patterns of LH secretion could be distinguished. In one experiment the high level of LH was maintained unchanged throughout sexual maturation while in another experiment LH secretion decreased significantly between days 11 and 28 of photostimulation. A strong correlation existed between testicular growth and the plasma FSH concentration. It was maximal during the phase of rapid testicular growth and decreased as spermiogenesis began. The pituitary FSH content increased during photostimulation. Castration caused a 20-fold rise in plasma FSH compared with that in intact quail. The change in LH concentration after castration was about eightfold. The changes in hormone secretion were strikingly similar to those found during sexual development and puberty in the rat."} {"id": "PMID:1270950", "title": "Ovine placental lactogen: acute effects on intermediary metabolism in pregnant and non-pregnant sheep.", "content": "The intravenous administration of ovine placental lactogen to pregnant and non-pregnant sheep produced significant acute decreases in plasma free fatty acid, glucose and amino nitrogen concentrations. Plasma insulin concentrations decreased 1 h after administration of ovine placental lactogen and then increased significantly above baseline concentrations. The results suggest that, like human placental lactogen, ovine placental lactogen is important in the modulation of intermediary metabolism during pregnancy. The sheep is an excellent animal model for the investigation of the physiology of placental lactogen.", "contents": "Ovine placental lactogen: acute effects on intermediary metabolism in pregnant and non-pregnant sheep. The intravenous administration of ovine placental lactogen to pregnant and non-pregnant sheep produced significant acute decreases in plasma free fatty acid, glucose and amino nitrogen concentrations. Plasma insulin concentrations decreased 1 h after administration of ovine placental lactogen and then increased significantly above baseline concentrations. The results suggest that, like human placental lactogen, ovine placental lactogen is important in the modulation of intermediary metabolism during pregnancy. The sheep is an excellent animal model for the investigation of the physiology of placental lactogen."} {"id": "PMID:1270951", "title": "Observations on the localization of recently synthesized catecholamines in chromaffin cells after the injection of L-(2,5,6-3H)dopa.", "content": "The fate of tl-[2, 5, 6-3h] dopa, and the intracellular localization of its metabolic products dopamine, noradrenaline and adrenaline, have been determined by the simultaneous use of assay techniques following separation of amines by chromatography and light and electron microscopic autoradiography. During the first 24 h after i.v. or i.p. injection of [3H] DOPA, synthesis of the above catecholamines occurred. Throughout this time the labelled amines were associated with chromaffin granules or immediately adjacent cytosol and not with either the Golgi complex or rough endoplasmic reticulum. Labelling of chromaffin granules occurred simultaneously throughout the cell and there was no evidence of regions containing recently labelled granules and others containing previously charged (older) granules. Adrenaline-storing cells took up [3H] DOPA and its products more rapidly and lost recently synthesized adrenaline more rapidly than noradrenaline-storing cells took up and stored their equivalent amines. This was in keeping with a more rapid turnover of catecholamines in adrenaline-storing elements.", "contents": "Observations on the localization of recently synthesized catecholamines in chromaffin cells after the injection of L-(2,5,6-3H)dopa. The fate of tl-[2, 5, 6-3h] dopa, and the intracellular localization of its metabolic products dopamine, noradrenaline and adrenaline, have been determined by the simultaneous use of assay techniques following separation of amines by chromatography and light and electron microscopic autoradiography. During the first 24 h after i.v. or i.p. injection of [3H] DOPA, synthesis of the above catecholamines occurred. Throughout this time the labelled amines were associated with chromaffin granules or immediately adjacent cytosol and not with either the Golgi complex or rough endoplasmic reticulum. Labelling of chromaffin granules occurred simultaneously throughout the cell and there was no evidence of regions containing recently labelled granules and others containing previously charged (older) granules. Adrenaline-storing cells took up [3H] DOPA and its products more rapidly and lost recently synthesized adrenaline more rapidly than noradrenaline-storing cells took up and stored their equivalent amines. This was in keeping with a more rapid turnover of catecholamines in adrenaline-storing elements."} {"id": "PMID:1270952", "title": "Experimental diabetes insipidus in a marsupial, Macropus eugenii (Desmarest).", "content": "A new method is described for placing lesions in the supraoptico-neurohypophysial tract to produce diabetes insipidus. The method is particularly useful with species such as Macropus eugenii in which different individuals show a large variation in relative skull measurements. The development of the diabetes insipidus syndrome in the tammar wallaby (Macropus eugenii) is shown to have essentially the same triphasic pattern of urine production as in eutherians. Increased values of adrenal corticosteroids (less than 16 mug/100 ml plasma) were observed in the oliguric interphase. This has not been previously reported and we suggest that these increased values are most probably due to potentiation of corticotrophic releasing factor by the uncontrolled release of vasopressin during this phase.", "contents": "Experimental diabetes insipidus in a marsupial, Macropus eugenii (Desmarest). A new method is described for placing lesions in the supraoptico-neurohypophysial tract to produce diabetes insipidus. The method is particularly useful with species such as Macropus eugenii in which different individuals show a large variation in relative skull measurements. The development of the diabetes insipidus syndrome in the tammar wallaby (Macropus eugenii) is shown to have essentially the same triphasic pattern of urine production as in eutherians. Increased values of adrenal corticosteroids (less than 16 mug/100 ml plasma) were observed in the oliguric interphase. This has not been previously reported and we suggest that these increased values are most probably due to potentiation of corticotrophic releasing factor by the uncontrolled release of vasopressin during this phase."} {"id": "PMID:1270958", "title": "Immunoreactive alpha- and beta-subunits of luteinizing hormone in human peripheral blood and follicular fluid throughout the menstrual cycle, and their effect on the secretion rate of progesterone by human granulosa cells in tissue culture.", "content": "The concentration of the common alpha-subunit of the glycoprotein hormones and of the beta-subunit of luteinizing hormone (LHbeta) in peripheral blood and follicular fluid was measured throughout the menstrual cycle, and the effects of these subunits, either alone or in combination, on the production of progesterone by human granulosa cells in tissue culture were investigated. Changes in the serum concentration of alpha-subunit and immunoreactive 'LHbeta-like' material throughout the menstrual cycle were similar to those of LH. The concentrations of the subunits before the mid-cycle gonadotrophin peak were not significantly different from those during the luteal phase of the menstrual cycle. Gel filtration of a pooled serum sample obtained at mid-cycle confirmed the presence of immunoreactive alpha-subunit together with intact LH; however, because of the cross-reactivity of LH in the LHbeta assay a distinct peak of LHbeta-subunit could not be demonstrated. In follicular fluid, alpha-subunit was detectable in large follicles (greater than or equal to 8 mm) throughout the menstrual cycle at concentrations similar to those found in serum. By contrast alpha-subunit in small follicles (less than 8mm) and 'LHbeta-like' material in all follicles were only detectable during or just after peak concentrations in peripheral plasma. The LH subunits did not increase the rate of progesterone secretion by human granulosa cells when each was added alone, even at concentrations five times higher than those in plasma. However, when both subunits were added simultaneously there was an increased rate of progesterone secretion comparable to that achieved with intact LH. It is concluded that the common alpha-subunit circulates in blood independently of the intact hormones, and that it is present in a proportion of developine Graafian follicles without affecting either the viability or biosynthetic potential of their granulosa cells. During the late follicular phase however, when both the alpha- and LHbeta-like subunits are present in follicular fluid, they may recombine and enhance steroid production by granulosa cells which are undergoing luteinization at this time.", "contents": "Immunoreactive alpha- and beta-subunits of luteinizing hormone in human peripheral blood and follicular fluid throughout the menstrual cycle, and their effect on the secretion rate of progesterone by human granulosa cells in tissue culture. The concentration of the common alpha-subunit of the glycoprotein hormones and of the beta-subunit of luteinizing hormone (LHbeta) in peripheral blood and follicular fluid was measured throughout the menstrual cycle, and the effects of these subunits, either alone or in combination, on the production of progesterone by human granulosa cells in tissue culture were investigated. Changes in the serum concentration of alpha-subunit and immunoreactive 'LHbeta-like' material throughout the menstrual cycle were similar to those of LH. The concentrations of the subunits before the mid-cycle gonadotrophin peak were not significantly different from those during the luteal phase of the menstrual cycle. Gel filtration of a pooled serum sample obtained at mid-cycle confirmed the presence of immunoreactive alpha-subunit together with intact LH; however, because of the cross-reactivity of LH in the LHbeta assay a distinct peak of LHbeta-subunit could not be demonstrated. In follicular fluid, alpha-subunit was detectable in large follicles (greater than or equal to 8 mm) throughout the menstrual cycle at concentrations similar to those found in serum. By contrast alpha-subunit in small follicles (less than 8mm) and 'LHbeta-like' material in all follicles were only detectable during or just after peak concentrations in peripheral plasma. The LH subunits did not increase the rate of progesterone secretion by human granulosa cells when each was added alone, even at concentrations five times higher than those in plasma. However, when both subunits were added simultaneously there was an increased rate of progesterone secretion comparable to that achieved with intact LH. It is concluded that the common alpha-subunit circulates in blood independently of the intact hormones, and that it is present in a proportion of developine Graafian follicles without affecting either the viability or biosynthetic potential of their granulosa cells. During the late follicular phase however, when both the alpha- and LHbeta-like subunits are present in follicular fluid, they may recombine and enhance steroid production by granulosa cells which are undergoing luteinization at this time."} {"id": "PMID:1270959", "title": "Androgen-controlled specific proteins in rat epididymis.", "content": "The pattern of proteins in the soluble fraction of the cytoplasm of the rat epididymis was studied by acrylamide gel electrophoresis. The components of five distinct bands, labelled A, B, C, D and E, were found to be sensitive to changes in androgen in the blood. Castration for 14 days produced a sharp decrease in the colour intensity of bands B-E when stained with Amido black. After 21 days of castration, bands D and E were undetectable, bands B and C were severely diminished and band A was more intense. Seven days of replacement with testosterone (1 mg/day) induced a return towards a normal pattern. The degree of restoration was inversely proportional to the duration of castration. Quantitation by densitometry showed that the relative contributions of bands B-E to the region A-E were 61% in the control rat, only 27% after 21 days of castration and 35% when testosterone was given between days 14 and 21 of castration. The components of bands A-E are presumed to be proteins since the electrophoretic pattern was altered by digestion with pronase but not by ribonuclease, phospholipase C or neuraminidase. Epididymides from castrated and androgen-treated castrated rats were incubated with 14C- and 3H-labelled mixed amino acids respectively. After co-electrophoresis the ratio 3H: 14C rose from a baseline of 2-5 in band B, 32 in band C and 7 in bands D and E. Molecular weights were estimated as 27900 for B, 23100 for C and 34400 for D. Band A had the same electrophoretic mobility as serum albumin. Bands B and C were also present in testicular cytosol. Bands D and E were only found in the epididymis, localized mainly within the lumen of the tubules. Bands B-E increased with age during sexual maturation, bands D and E became detectable in the 20-day-old rats. Preliminary evidence indicates that the proteins in bands C, D and E can be removed from caput spermatozoa by washing.", "contents": "Androgen-controlled specific proteins in rat epididymis. The pattern of proteins in the soluble fraction of the cytoplasm of the rat epididymis was studied by acrylamide gel electrophoresis. The components of five distinct bands, labelled A, B, C, D and E, were found to be sensitive to changes in androgen in the blood. Castration for 14 days produced a sharp decrease in the colour intensity of bands B-E when stained with Amido black. After 21 days of castration, bands D and E were undetectable, bands B and C were severely diminished and band A was more intense. Seven days of replacement with testosterone (1 mg/day) induced a return towards a normal pattern. The degree of restoration was inversely proportional to the duration of castration. Quantitation by densitometry showed that the relative contributions of bands B-E to the region A-E were 61% in the control rat, only 27% after 21 days of castration and 35% when testosterone was given between days 14 and 21 of castration. The components of bands A-E are presumed to be proteins since the electrophoretic pattern was altered by digestion with pronase but not by ribonuclease, phospholipase C or neuraminidase. Epididymides from castrated and androgen-treated castrated rats were incubated with 14C- and 3H-labelled mixed amino acids respectively. After co-electrophoresis the ratio 3H: 14C rose from a baseline of 2-5 in band B, 32 in band C and 7 in bands D and E. Molecular weights were estimated as 27900 for B, 23100 for C and 34400 for D. Band A had the same electrophoretic mobility as serum albumin. Bands B and C were also present in testicular cytosol. Bands D and E were only found in the epididymis, localized mainly within the lumen of the tubules. Bands B-E increased with age during sexual maturation, bands D and E became detectable in the 20-day-old rats. Preliminary evidence indicates that the proteins in bands C, D and E can be removed from caput spermatozoa by washing."} {"id": "PMID:1270960", "title": "Effects of androgens, oestrogens and deoxycorticosterone acetate on plasma concentrations of luteinizing hormone in laying hens.", "content": "Testosterone, androstenedione, oestrone, oestradiol-17beta or deoxycorticosterone acetate (DOCA) were injected intramuscularly at several dose-levels and at various stages of the ovulatory cycle, and subsequent changes in plasma LH concentration were measured by radioimmunoassay. In 19 out of 24 hens, injection of 0.1, 0.5 or 1.0 mg DOCA/kg resulted in a mean maximal increase in plasma LH concentration of between 0.47 and 2.10 ng/ml. The magnitude of this response was not related to either the dose or the stage of the cycle at which the DOCA was injected. In the remaining five hens DOCA failed to stimulate LH secretion. Injection of either androstenedione, oestrone or oestradiol did not result in any increase in LH level in the circulation. In contrast, injection of 0.5, 1.0 or 2.0 mg testosterone/kg between 22 and 26 h after the terminal ovulation of a sequence resulted in mean maximal incremental changes in plasma LH level of 1.98 +/- 0.17, 2.17 +/- 0.21 and 2.41 +/- 0.31 (S.E.M.) ng/ml from pre-injection values of 1.38 +/- 0.16, 1.58 +/- 0.30 and 1.43 +/- 0.39 ng/ml (n=7, 6 and 5, respectively). The interval between the injection and the resulting rise in LH level was inversely proportional to the dose. The same doses of testosterone injected between 0 and 8 h after ovulation failed to stimulate LH secretion. There was also no significant increase in LH levels after injection of 0.5 and 1.0 mg testosterone/kg between 8 and 9 h after ovulation. However, injection of 2 mg testosterone/kg at this time resulted in a small but significant (P is less than 0.05) increase in LH levels. Since the largest ovarian follicle is more mature at 22-26 h after ovulation than at 0-9 h after ovulation, the ability of testosterone to cause the release of LH therefore appears to depend upon the degree of maturation of the ovarian follicle next due to ovulate.", "contents": "Effects of androgens, oestrogens and deoxycorticosterone acetate on plasma concentrations of luteinizing hormone in laying hens. Testosterone, androstenedione, oestrone, oestradiol-17beta or deoxycorticosterone acetate (DOCA) were injected intramuscularly at several dose-levels and at various stages of the ovulatory cycle, and subsequent changes in plasma LH concentration were measured by radioimmunoassay. In 19 out of 24 hens, injection of 0.1, 0.5 or 1.0 mg DOCA/kg resulted in a mean maximal increase in plasma LH concentration of between 0.47 and 2.10 ng/ml. The magnitude of this response was not related to either the dose or the stage of the cycle at which the DOCA was injected. In the remaining five hens DOCA failed to stimulate LH secretion. Injection of either androstenedione, oestrone or oestradiol did not result in any increase in LH level in the circulation. In contrast, injection of 0.5, 1.0 or 2.0 mg testosterone/kg between 22 and 26 h after the terminal ovulation of a sequence resulted in mean maximal incremental changes in plasma LH level of 1.98 +/- 0.17, 2.17 +/- 0.21 and 2.41 +/- 0.31 (S.E.M.) ng/ml from pre-injection values of 1.38 +/- 0.16, 1.58 +/- 0.30 and 1.43 +/- 0.39 ng/ml (n=7, 6 and 5, respectively). The interval between the injection and the resulting rise in LH level was inversely proportional to the dose. The same doses of testosterone injected between 0 and 8 h after ovulation failed to stimulate LH secretion. There was also no significant increase in LH levels after injection of 0.5 and 1.0 mg testosterone/kg between 8 and 9 h after ovulation. However, injection of 2 mg testosterone/kg at this time resulted in a small but significant (P is less than 0.05) increase in LH levels. Since the largest ovarian follicle is more mature at 22-26 h after ovulation than at 0-9 h after ovulation, the ability of testosterone to cause the release of LH therefore appears to depend upon the degree of maturation of the ovarian follicle next due to ovulate."} {"id": "PMID:1270961", "title": "Effects of postnatal thyroxine administration on brain development, response to postnatal androgen and thyroid regulation in female rats.", "content": "Some developmental and functional manifestations of thyroxine (T4) administered on the first 2 days of postnatal life were studied in the female rat. Brain myelinogenesis estimated by brain esterified cholesterol concentration, and brain myelin age estimated by brain total cholesterol concentration, were subsequently determined. Thyroxine treatment resulted in a greater concentration of esterified cholesterol in the brain that saline treatment, but the latter appeared to delay the normal increase shown by non-injected controls. Thyroxine treatment resulted in total and free cholesterol levels similar to those of non-injected controls, these again being greater than those in saline-treated rats. Cholesterol concentrations in liver and serum were not affected by T4 or saline treatment. Administration of T4 to female rats before administration of 1-25 mg testosterone propionate on day 7 resulted in an ovarian and uterine weight response to human chorionic gonadotrophin (HCG, 1 i.u./day on days 23-26) on day 27 that was greater than that in litter-mates given saline at birth before testosterone propionate and HCG treatment. Postnatal T4 treatment alone in the female was also associated with a reduced thyroid and pituitary gland enlargement after 7 days of propylthiouracil feeding (0-015% in tap water, days 24-31 of life) when compared with either saline or non-injected controls.", "contents": "Effects of postnatal thyroxine administration on brain development, response to postnatal androgen and thyroid regulation in female rats. Some developmental and functional manifestations of thyroxine (T4) administered on the first 2 days of postnatal life were studied in the female rat. Brain myelinogenesis estimated by brain esterified cholesterol concentration, and brain myelin age estimated by brain total cholesterol concentration, were subsequently determined. Thyroxine treatment resulted in a greater concentration of esterified cholesterol in the brain that saline treatment, but the latter appeared to delay the normal increase shown by non-injected controls. Thyroxine treatment resulted in total and free cholesterol levels similar to those of non-injected controls, these again being greater than those in saline-treated rats. Cholesterol concentrations in liver and serum were not affected by T4 or saline treatment. Administration of T4 to female rats before administration of 1-25 mg testosterone propionate on day 7 resulted in an ovarian and uterine weight response to human chorionic gonadotrophin (HCG, 1 i.u./day on days 23-26) on day 27 that was greater than that in litter-mates given saline at birth before testosterone propionate and HCG treatment. Postnatal T4 treatment alone in the female was also associated with a reduced thyroid and pituitary gland enlargement after 7 days of propylthiouracil feeding (0-015% in tap water, days 24-31 of life) when compared with either saline or non-injected controls."} {"id": "PMID:1270962", "title": "Effects of sexual activity on luteinizing hormone and testosterone levels in the adult male rabbit.", "content": "Sexually mature New Zealand White male rabbits were subjected to various sexual stimulation procedures. Plasma samples were obtained through an indwelling catheter in the central ear artery and analysed for LH and testosterone using specific radioimmunoassays. Coitus and exposure to females occasionally led to increases in testosterone levels which were usually preceded by a rise in LH. Increases in hormone concentration were not significantly different from those of rabbits which did not mate or which were isolated from females. These results suggest that coitus in the male rabbit does not cause the massive increase in LH concentration which is known to occur in the female.", "contents": "Effects of sexual activity on luteinizing hormone and testosterone levels in the adult male rabbit. Sexually mature New Zealand White male rabbits were subjected to various sexual stimulation procedures. Plasma samples were obtained through an indwelling catheter in the central ear artery and analysed for LH and testosterone using specific radioimmunoassays. Coitus and exposure to females occasionally led to increases in testosterone levels which were usually preceded by a rise in LH. Increases in hormone concentration were not significantly different from those of rabbits which did not mate or which were isolated from females. These results suggest that coitus in the male rabbit does not cause the massive increase in LH concentration which is known to occur in the female."} {"id": "PMID:1270963", "title": "Plasma luteinizing hormone and progesterone in the adult female pig during the oestrous cycles, late pregnancy and lactation, and after ovariectomy and pentobarbitone treatment.", "content": "In a series of experiments on female miniature pigs, the pattern of plasma LH and progesterone levels during the oestrous cycle, late pregnancy and lactation and after ovariectomy were characterized, and the effect of pentobarbitone treatment was tested. The preovulatory surge of LH occurred in seven out of eight animals between 00.00 and 12.0 h on day 0 of the oestrous cycle (day 1 of standing heat). Plasma progesterone strated to decline 8 days before oestrus and reached its lowest value 5 days before the preovulatory LH peak. Increases in progesteron concentration were already noticeable 48 h after the LH surge. During late pregnancy, parturition and lactation, plasma LH was low and showed only minor fluctuations, while plasma progesterone declined 4 to 5 days before parturition. Both hormones remained at low levels throughout lactation. Three weeks before parturition increases in LH were always followed by an increase in progesterone. This dependency was greatly diminished immediately before delivery. Four to 12 days after weaning the animals came into oestrus which was followed by an increase in LH and later an increase in progesterone concentrations. Ovariectomy during dioestrus resulted in a steady increase in plasma LH levels of 35-39 days. Ovariectomy caused abortion if performed on day 100 of pregnancy. It was followed by a rapid increase of plasma LH concentration. Normal parturition (around day 115) and lactation took place when animals were spayed on day 112 of pregnancy. In this case, plasma LH levels remained even lower than before ovariectomy as long as lactation was maintained. Immediately after weaning a rapid increase in the normal postovariectomy pattern of LH secretion was observed. Pentobarbitone anaesthesia (30-35 mg/kg body wt, initial dose), during pro-oestrusoestrus, for less than 5 h had no effect on the preovulatory LH increase. However, pentobarbitone anaesthesia for more than 6 h inhibitied the LH peak and ovulation if the animal was under deep anaesthesia before 24.00 h on the day before oestrus. Pentobarbitone treatment of ovariectomized pigs resulted in a clear decrease in LH levels 40 min after a single i.v. dose.", "contents": "Plasma luteinizing hormone and progesterone in the adult female pig during the oestrous cycles, late pregnancy and lactation, and after ovariectomy and pentobarbitone treatment. In a series of experiments on female miniature pigs, the pattern of plasma LH and progesterone levels during the oestrous cycle, late pregnancy and lactation and after ovariectomy were characterized, and the effect of pentobarbitone treatment was tested. The preovulatory surge of LH occurred in seven out of eight animals between 00.00 and 12.0 h on day 0 of the oestrous cycle (day 1 of standing heat). Plasma progesterone strated to decline 8 days before oestrus and reached its lowest value 5 days before the preovulatory LH peak. Increases in progesteron concentration were already noticeable 48 h after the LH surge. During late pregnancy, parturition and lactation, plasma LH was low and showed only minor fluctuations, while plasma progesterone declined 4 to 5 days before parturition. Both hormones remained at low levels throughout lactation. Three weeks before parturition increases in LH were always followed by an increase in progesterone. This dependency was greatly diminished immediately before delivery. Four to 12 days after weaning the animals came into oestrus which was followed by an increase in LH and later an increase in progesterone concentrations. Ovariectomy during dioestrus resulted in a steady increase in plasma LH levels of 35-39 days. Ovariectomy caused abortion if performed on day 100 of pregnancy. It was followed by a rapid increase of plasma LH concentration. Normal parturition (around day 115) and lactation took place when animals were spayed on day 112 of pregnancy. In this case, plasma LH levels remained even lower than before ovariectomy as long as lactation was maintained. Immediately after weaning a rapid increase in the normal postovariectomy pattern of LH secretion was observed. Pentobarbitone anaesthesia (30-35 mg/kg body wt, initial dose), during pro-oestrusoestrus, for less than 5 h had no effect on the preovulatory LH increase. However, pentobarbitone anaesthesia for more than 6 h inhibitied the LH peak and ovulation if the animal was under deep anaesthesia before 24.00 h on the day before oestrus. Pentobarbitone treatment of ovariectomized pigs resulted in a clear decrease in LH levels 40 min after a single i.v. dose."} {"id": "PMID:1270964", "title": "Comparison of the redox bioassay with other assays for luteinizing hormone.", "content": "The cytochemical (redox) bioassay for LH has been compared with established LH assays. Measurements made by redox bioassays were considerably lower than those made by radioimmunoassay in human female plasma samples obtained at mid-cycle. There was no apparent relationship between measurements on incubation media from cultures of sheep pituitary glands made by redox bioassay and the ovarian ascorbic acid depletion (OAAD) assay. After polyacrylamide gel electrophoresis of a crude extract of a human pituitary gland, redox LH measurements were lower than those of the OAAD assay and radioimmunoassay in the cathodal segments of the gel. By contrast, there was reasonable agreement between LH measurements made by radioimmunoassay and redox assay in cathodal fractions from gel electrophroesis of a purified pituitary LH preparation. Follicle-stimulating hormone, and the alpha- and beta-subunits of LH depressed the response of intact LH in the redox assay; this might explain the relatively low levels of LH measured by redox assay in some of the experiments described. Which type of assay best reflects the biological activity of LH in man remains to be determined.", "contents": "Comparison of the redox bioassay with other assays for luteinizing hormone. The cytochemical (redox) bioassay for LH has been compared with established LH assays. Measurements made by redox bioassays were considerably lower than those made by radioimmunoassay in human female plasma samples obtained at mid-cycle. There was no apparent relationship between measurements on incubation media from cultures of sheep pituitary glands made by redox bioassay and the ovarian ascorbic acid depletion (OAAD) assay. After polyacrylamide gel electrophoresis of a crude extract of a human pituitary gland, redox LH measurements were lower than those of the OAAD assay and radioimmunoassay in the cathodal segments of the gel. By contrast, there was reasonable agreement between LH measurements made by radioimmunoassay and redox assay in cathodal fractions from gel electrophroesis of a purified pituitary LH preparation. Follicle-stimulating hormone, and the alpha- and beta-subunits of LH depressed the response of intact LH in the redox assay; this might explain the relatively low levels of LH measured by redox assay in some of the experiments described. Which type of assay best reflects the biological activity of LH in man remains to be determined."} {"id": "PMID:1270965", "title": "Seasonal variation in the episodic secretion of luteinizing hormone and testosterone in the ram.", "content": "Rams of an ancient breed of domestic sheep (Soay) were housed under artificial lighting conditions to study the way in which the secretion of LH and testosterone changes in relation to the mating season. Conspicuous changes were found in the short-term fluctuations in plasma LH concentrations related to the cycle of testis growth and regression; serial blood samples collected at short intervals revealed episodic peaks in plasma LH at all times, but there were changes in the frequency (lowest when the testes were regressed and highest when fully active), amplitude (lowest at the peak of testis activity, and highest during the developing phase), and duration of the peaks (shortest when the testes were regressed). In addition, the basal levels changed from being lowest in the regressed phase of the testis cycle, and highest when the gonads were most active. Plasma testosterone concentrations changed in parallel with the cycle of testis size and were correlated with the fluctuating levels of LH. Each episodic peak in plasma LH was associated with an increase in the levels of testosterone, beginning after 0-30 min and rising to a peak at 60-90 min; the speed and magnitude of the response being greatest when the testes were largest, but was not correlated with the magnitude of the LH change. Injections of LH releasing hormone (5 mug) stimulated an increase in plasma LH and testosterone proportional to the endogenous fluctuations in the hormones at the various stages of the seasonal cycle; LH concentrations were raised to supra-physiological levels after the injections, while testosterone concentrations seldom exceeded the normal peak values at any stage. These observations are used to discuss the role of the hypothalamus in the control of male seasonality with emphasis on the dynamic interplay between the hypothalamus, pituitary and testis.", "contents": "Seasonal variation in the episodic secretion of luteinizing hormone and testosterone in the ram. Rams of an ancient breed of domestic sheep (Soay) were housed under artificial lighting conditions to study the way in which the secretion of LH and testosterone changes in relation to the mating season. Conspicuous changes were found in the short-term fluctuations in plasma LH concentrations related to the cycle of testis growth and regression; serial blood samples collected at short intervals revealed episodic peaks in plasma LH at all times, but there were changes in the frequency (lowest when the testes were regressed and highest when fully active), amplitude (lowest at the peak of testis activity, and highest during the developing phase), and duration of the peaks (shortest when the testes were regressed). In addition, the basal levels changed from being lowest in the regressed phase of the testis cycle, and highest when the gonads were most active. Plasma testosterone concentrations changed in parallel with the cycle of testis size and were correlated with the fluctuating levels of LH. Each episodic peak in plasma LH was associated with an increase in the levels of testosterone, beginning after 0-30 min and rising to a peak at 60-90 min; the speed and magnitude of the response being greatest when the testes were largest, but was not correlated with the magnitude of the LH change. Injections of LH releasing hormone (5 mug) stimulated an increase in plasma LH and testosterone proportional to the endogenous fluctuations in the hormones at the various stages of the seasonal cycle; LH concentrations were raised to supra-physiological levels after the injections, while testosterone concentrations seldom exceeded the normal peak values at any stage. These observations are used to discuss the role of the hypothalamus in the control of male seasonality with emphasis on the dynamic interplay between the hypothalamus, pituitary and testis."} {"id": "PMID:1270966", "title": "Activity of steroid C-17,20 lyase in the ovine placenta: effect of exposure to foetal glucocorticoid.", "content": "Microsomal fractions isolated from post-partum ovine placentae catalysed the synthesis of [3H]oestrone and [3H]oestradiol from [3H]17alpha-hydroxyprogesterone and NADPH; oestrone and oestradiol were formed in a ratio of approximately 50:1. The expected intermediate, [3H]androstenedione, did not accumulate during these incubations but was shown by trapping experiments to be the intermediate involved. Mean (+/- s.d.) uields of [3H]oestrone (% conversion of substrate) during incubation for 1 h of placentae from five animals in late pregnancy before the onset of labour, from five animals which delivered spontaneously at term and from four animals in which labour was induced by administration dexamethasone to the foetus were: in tissue obtained before labour, 3-2+/-0-44; in tissue obtained after the spontaneous onset of labour, 20-6+/-10-2 (P less than 0-01) and in tissue obtained after dexamethasone-induced labour, 24-4+/-2-13 (P less than 0-0001). This increase in oestrone synthesis suggests activation of steroid C-17,20 lyase, since this is the step limiting the rate of synthesis of oestrone in vitro. The enzyme is probably activated by foetal glucocorticoid. The findings are discussed in relation to the site of synthesis of oestrogens which in the sheep increase in concentration in the peripheral circulation at term, and with reference to a possible mechanism by which foetal glucocorticoid may control the onset of labour in this species.", "contents": "Activity of steroid C-17,20 lyase in the ovine placenta: effect of exposure to foetal glucocorticoid. Microsomal fractions isolated from post-partum ovine placentae catalysed the synthesis of [3H]oestrone and [3H]oestradiol from [3H]17alpha-hydroxyprogesterone and NADPH; oestrone and oestradiol were formed in a ratio of approximately 50:1. The expected intermediate, [3H]androstenedione, did not accumulate during these incubations but was shown by trapping experiments to be the intermediate involved. Mean (+/- s.d.) uields of [3H]oestrone (% conversion of substrate) during incubation for 1 h of placentae from five animals in late pregnancy before the onset of labour, from five animals which delivered spontaneously at term and from four animals in which labour was induced by administration dexamethasone to the foetus were: in tissue obtained before labour, 3-2+/-0-44; in tissue obtained after the spontaneous onset of labour, 20-6+/-10-2 (P less than 0-01) and in tissue obtained after dexamethasone-induced labour, 24-4+/-2-13 (P less than 0-0001). This increase in oestrone synthesis suggests activation of steroid C-17,20 lyase, since this is the step limiting the rate of synthesis of oestrone in vitro. The enzyme is probably activated by foetal glucocorticoid. The findings are discussed in relation to the site of synthesis of oestrogens which in the sheep increase in concentration in the peripheral circulation at term, and with reference to a possible mechanism by which foetal glucocorticoid may control the onset of labour in this species."} {"id": "PMID:1270967", "title": "Effects of ferrous ions on preoptic area neurones and luteinizing hormone secretion in the rat.", "content": "Ferrous ions (Fe2+) were applied by microiontophoresis of 29 neurones recordid from the forebrain of ten pro-oestrous rats. The spontaneous activity of 24 cells was reduced by Fe2+ and five units did not respond. No excitations were observed. Reproducible responses could not be obtained with ferric ions (Fe3+). Microinjection of 1 mul 200 mM-Fe2+ into the preoptic area of eight pro-oestrous rats produced a sharp increase in plasma LH levels. Similar treatment with saline was without effect. Rats anaesthetized with sodium pentobarbitone during the early afternoon of pro-oestrus ovulated overnight when injected with both Fe2+ and Fe3+. The experiments do not confirm the widely held belief that raised plasma LH levels following deposition of iron in the rostral hypothalamus result from increased firing of nerve cells.", "contents": "Effects of ferrous ions on preoptic area neurones and luteinizing hormone secretion in the rat. Ferrous ions (Fe2+) were applied by microiontophoresis of 29 neurones recordid from the forebrain of ten pro-oestrous rats. The spontaneous activity of 24 cells was reduced by Fe2+ and five units did not respond. No excitations were observed. Reproducible responses could not be obtained with ferric ions (Fe3+). Microinjection of 1 mul 200 mM-Fe2+ into the preoptic area of eight pro-oestrous rats produced a sharp increase in plasma LH levels. Similar treatment with saline was without effect. Rats anaesthetized with sodium pentobarbitone during the early afternoon of pro-oestrus ovulated overnight when injected with both Fe2+ and Fe3+. The experiments do not confirm the widely held belief that raised plasma LH levels following deposition of iron in the rostral hypothalamus result from increased firing of nerve cells."} {"id": "PMID:1270968", "title": "Purification and properties of the subunits of human pituitary follicle-stimulating hormone.", "content": "Highly purified human pituitary FSH was partially dissociated by treatment with 8M-urea, and alpha- and beta-subunits were isolated by ion-exchange chromatography and gel filtration. Tests of biological activity by in-vivo assays and in-vitro radioreceptor assays were in good agreement and showed that preparations of isolated alpha-subunit had less than 1%, and beta-subunit from 2 to 10% of the FSH activity of the intact hormone. In contrast to results reported elsewhere, most of the subunit preparations reassociated with counterpart subunit to regain biological activity equal to that of intact FSH (around 160 mg NIH-FSH-S1/mg). The intact FSH recovered as a by-product after isolation of subunits was of high biological activity, and its LH contamination was reduced by more than 90% when compared with thepurified FSH starting material. The subunits are relatively inactive in a radioimmunoassay specific for intact FSH. Sialic acid and tryptophan determinations indicated that both subunits contain sialic acid and that tryptophan is present only in the beta-subunit.", "contents": "Purification and properties of the subunits of human pituitary follicle-stimulating hormone. Highly purified human pituitary FSH was partially dissociated by treatment with 8M-urea, and alpha- and beta-subunits were isolated by ion-exchange chromatography and gel filtration. Tests of biological activity by in-vivo assays and in-vitro radioreceptor assays were in good agreement and showed that preparations of isolated alpha-subunit had less than 1%, and beta-subunit from 2 to 10% of the FSH activity of the intact hormone. In contrast to results reported elsewhere, most of the subunit preparations reassociated with counterpart subunit to regain biological activity equal to that of intact FSH (around 160 mg NIH-FSH-S1/mg). The intact FSH recovered as a by-product after isolation of subunits was of high biological activity, and its LH contamination was reduced by more than 90% when compared with thepurified FSH starting material. The subunits are relatively inactive in a radioimmunoassay specific for intact FSH. Sialic acid and tryptophan determinations indicated that both subunits contain sialic acid and that tryptophan is present only in the beta-subunit."} {"id": "PMID:1270971", "title": "Facilitation of human tobacco self-administration by ethanol: a behavioral analysis.", "content": "The effect of ethanol on the cigarette smoking of alcoholic subjects was studied in a residential laboratory. During daily 6-hr sessions, cigarettes were obtained either by request to the ward staff or by operation of a lever (fixed-ratio 5 or 10). In a mixed sequence across days, sessions involved ingestion of either vehicle (orange juice or vehicle plus ethanol (133.7 g). During ethanol sessions, the rate of cigarette smoking increased from 26% to 117% of vehicle levels. A series of control studies eliminated a number of potential behavorial mechanisms for the observed effect and indicated that the ethanol-induced increase in cigarette smoking occurred under a variety of experimental conditions: (1) when smoking could not occur concurrently with ethanol or vehicle consumption; (2) when subjects were not allowed to socialize; (3) when ingestion of ethanol or vehicle was scheduled for a number of consecutive days; (4) when various doses of ethanol were administered under blind conditions. In control experiments, weighing unsmoked tobacco and counting the number of puffs per cigarette indicated the effect was not due to smoking less of each cigarette. The effect was not limited to the experimental sessions alone, since total daily smoking was higher on ethanol days than vehicle days.", "contents": "Facilitation of human tobacco self-administration by ethanol: a behavioral analysis. The effect of ethanol on the cigarette smoking of alcoholic subjects was studied in a residential laboratory. During daily 6-hr sessions, cigarettes were obtained either by request to the ward staff or by operation of a lever (fixed-ratio 5 or 10). In a mixed sequence across days, sessions involved ingestion of either vehicle (orange juice or vehicle plus ethanol (133.7 g). During ethanol sessions, the rate of cigarette smoking increased from 26% to 117% of vehicle levels. A series of control studies eliminated a number of potential behavorial mechanisms for the observed effect and indicated that the ethanol-induced increase in cigarette smoking occurred under a variety of experimental conditions: (1) when smoking could not occur concurrently with ethanol or vehicle consumption; (2) when subjects were not allowed to socialize; (3) when ingestion of ethanol or vehicle was scheduled for a number of consecutive days; (4) when various doses of ethanol were administered under blind conditions. In control experiments, weighing unsmoked tobacco and counting the number of puffs per cigarette indicated the effect was not due to smoking less of each cigarette. The effect was not limited to the experimental sessions alone, since total daily smoking was higher on ethanol days than vehicle days."} {"id": "PMID:1270972", "title": "Some effects of delta-amphetamine and pentobarbital on performance under a long fixed-interval schedule.", "content": "The effects of delta-amphetamine and pentobarbital were studied on performance during 3-hr sessions under fixed-interval 60-min schedules of food presentation. Low doses of delta-amphetamine increased rates of responding and higher doses decreased rates of responding, both during the entire 3-hr session and during each of the individual fixed intervals. Pentobarbital produced little effect on rates of responding averaged over the 3-r session, but it decreased rates during the first fixed interval and increased them during the second and third fixed intervals. The effects of delta-amphetamine were shown to be dependent on the control rate of responding, as has been shown with shorter fixed-interval values. Analysis of delta-amphetamine effects in terms of the point at which the probability of responding is greater than zero was not descriptive of overall fixed-interval performance.", "contents": "Some effects of delta-amphetamine and pentobarbital on performance under a long fixed-interval schedule. The effects of delta-amphetamine and pentobarbital were studied on performance during 3-hr sessions under fixed-interval 60-min schedules of food presentation. Low doses of delta-amphetamine increased rates of responding and higher doses decreased rates of responding, both during the entire 3-hr session and during each of the individual fixed intervals. Pentobarbital produced little effect on rates of responding averaged over the 3-r session, but it decreased rates during the first fixed interval and increased them during the second and third fixed intervals. The effects of delta-amphetamine were shown to be dependent on the control rate of responding, as has been shown with shorter fixed-interval values. Analysis of delta-amphetamine effects in terms of the point at which the probability of responding is greater than zero was not descriptive of overall fixed-interval performance."} {"id": "PMID:1270973", "title": "Abnormalities in the differentiation and cellular properties of hyperplastic lens epithelium from strains of chickens selected for high growth rate.", "content": "Similar morphological abnormalities of the lens of the eye of two unrelated strains of chicks, both of which had been selected for high growth rate, were found to be associated with epithelial cells showing marked deviations from the normal in cell surface properties, mitotic rate, capacity for differentiation, and in DNA, RNA and protein metabolism. The relationship between these modified properties and the observed morphology is discussed.", "contents": "Abnormalities in the differentiation and cellular properties of hyperplastic lens epithelium from strains of chickens selected for high growth rate. Similar morphological abnormalities of the lens of the eye of two unrelated strains of chicks, both of which had been selected for high growth rate, were found to be associated with epithelial cells showing marked deviations from the normal in cell surface properties, mitotic rate, capacity for differentiation, and in DNA, RNA and protein metabolism. The relationship between these modified properties and the observed morphology is discussed."} {"id": "PMID:1270974", "title": "Embryogenesis of an insect nervous system. I. A map of the thoracic and abdominal neuroblasts in Locusta migratoria.", "content": "Maps of the thoracic and abdominal neuroblasts have been prepared by reconstruction from serial sections of timed Locusta migratoria embryos. The maps are bilaterally symmetrical, periodic and consistent for embryos of the same age, with a fundamental arrangement of 7 rows of 4-10 cells plus 1 median neuroblast per segment. A map of 60 + 1 cells is repeated in each of the three thoracic segments, with an additional median cell developing late at the anterior end of the prothorax. The arrangement in the abdomen is similar, with 56 + 1 cells per segment. Neuroblasts differentiate and subsequently degenerate in an antero-posterior sequence, but construction of the thoracic ganglia involves a delayed degeneration of part of the original set in these segments. The maps show that the neuroblasts are as reliable in their number and arrangement as the adult cells they produce. The number of neuroblasts used in constructing the relatively complex thoracic ganglia is similar to that which produces the simpler abdominal ganglia. Some motorneurons have the same parent neuroblast. The maps are intended as a first step in an analysis of the relation between the progeny of different neuroblasts and the family of neurons which each neuroblast produces.", "contents": "Embryogenesis of an insect nervous system. I. A map of the thoracic and abdominal neuroblasts in Locusta migratoria. Maps of the thoracic and abdominal neuroblasts have been prepared by reconstruction from serial sections of timed Locusta migratoria embryos. The maps are bilaterally symmetrical, periodic and consistent for embryos of the same age, with a fundamental arrangement of 7 rows of 4-10 cells plus 1 median neuroblast per segment. A map of 60 + 1 cells is repeated in each of the three thoracic segments, with an additional median cell developing late at the anterior end of the prothorax. The arrangement in the abdomen is similar, with 56 + 1 cells per segment. Neuroblasts differentiate and subsequently degenerate in an antero-posterior sequence, but construction of the thoracic ganglia involves a delayed degeneration of part of the original set in these segments. The maps show that the neuroblasts are as reliable in their number and arrangement as the adult cells they produce. The number of neuroblasts used in constructing the relatively complex thoracic ganglia is similar to that which produces the simpler abdominal ganglia. Some motorneurons have the same parent neuroblast. The maps are intended as a first step in an analysis of the relation between the progeny of different neuroblasts and the family of neurons which each neuroblast produces."} {"id": "PMID:1270975", "title": "The formation of the gonadal ridge in Xenopus laevis. I. A light and transmission electron microscope study.", "content": "In Xenopus laevis tadpoles, between stages 44 and 49 (Nieuwkoop & Faber, 1956), the primordial germ cells (PGCs) migrate from the dorsal mesentery of the gut to the site of the presumptive GD gonadal ridge. This paper describes the process at the light- and electronmicroscope levels. The PGCs in the mesentery, which at first are very large and yolk-laden, seem to lie entirely within the cellular matrix of the mesentery, although this is not obvious in light micrographs. Where the PGCs bulge out into the coelomic cavity, they stretch the somatic cell covering to a thin, cytoplasmic layer. The somatic cells of the mesentery are held together around them at this stage by well-differentiated desmosomes. At this, and subsequent stages, the PGCs have cytoplasmic processes, roughly the size of microvilli, which are irregularly distributed over their surfaces, and which are inserted between surrounding somatic cells. Whether these processes play any role in locomotion or exploration of the substrate is uncertain. As the PGCs move laterally from the root of the mesentery to the presumptive gonadal ridge, the coelomic lining cells which cover them, initially with a very thin squamous layer, differentiate to form the cuboidal cells of the germinal epithelium. Several interesting ultrastructural features of these cells, and the PGCs, are described, particularly in the light of their surface interaction. In the light of the morphological data presented here, particularly of the cell surfaces involved, we conclude that both active locomotion by the PGCs and passive movement by the morphogenetic movements of the cells around them contribute to the establishment of the early gonadal ridge.", "contents": "The formation of the gonadal ridge in Xenopus laevis. I. A light and transmission electron microscope study. In Xenopus laevis tadpoles, between stages 44 and 49 (Nieuwkoop & Faber, 1956), the primordial germ cells (PGCs) migrate from the dorsal mesentery of the gut to the site of the presumptive GD gonadal ridge. This paper describes the process at the light- and electronmicroscope levels. The PGCs in the mesentery, which at first are very large and yolk-laden, seem to lie entirely within the cellular matrix of the mesentery, although this is not obvious in light micrographs. Where the PGCs bulge out into the coelomic cavity, they stretch the somatic cell covering to a thin, cytoplasmic layer. The somatic cells of the mesentery are held together around them at this stage by well-differentiated desmosomes. At this, and subsequent stages, the PGCs have cytoplasmic processes, roughly the size of microvilli, which are irregularly distributed over their surfaces, and which are inserted between surrounding somatic cells. Whether these processes play any role in locomotion or exploration of the substrate is uncertain. As the PGCs move laterally from the root of the mesentery to the presumptive gonadal ridge, the coelomic lining cells which cover them, initially with a very thin squamous layer, differentiate to form the cuboidal cells of the germinal epithelium. Several interesting ultrastructural features of these cells, and the PGCs, are described, particularly in the light of their surface interaction. In the light of the morphological data presented here, particularly of the cell surfaces involved, we conclude that both active locomotion by the PGCs and passive movement by the morphogenetic movements of the cells around them contribute to the establishment of the early gonadal ridge."} {"id": "PMID:1270976", "title": "The formation of the gonadal ridge in Xenopus laevis. II. A scanning electron microscope study.", "content": "This paper studies the surface morphology of the developing gonadal ridge in X. laevis between stages 44 and 49 (Nieuwkoop & Faber, 1956). During this period the primordial germ cells (PGCs) move laterally from the dorsal mesentery of the gut to the position of the presumptive gonadal ridge. As they do so the coelomic lining cells lateral to the mesentery differentiate into a specialized, longitudinally orientated band, stretching nearly the full length of the dorsal mesentery on each side. The PGCs migrate beneath this band of cells, which thus becomes the germinal epithelium of the gonadal ridge. We have demonstrated by irradiation experiments that this specialized band of cells can differentiate independently, in the absence of the PGCs.", "contents": "The formation of the gonadal ridge in Xenopus laevis. II. A scanning electron microscope study. This paper studies the surface morphology of the developing gonadal ridge in X. laevis between stages 44 and 49 (Nieuwkoop & Faber, 1956). During this period the primordial germ cells (PGCs) move laterally from the dorsal mesentery of the gut to the position of the presumptive gonadal ridge. As they do so the coelomic lining cells lateral to the mesentery differentiate into a specialized, longitudinally orientated band, stretching nearly the full length of the dorsal mesentery on each side. The PGCs migrate beneath this band of cells, which thus becomes the germinal epithelium of the gonadal ridge. We have demonstrated by irradiation experiments that this specialized band of cells can differentiate independently, in the absence of the PGCs."} {"id": "PMID:1270977", "title": "The effect of 5-bromodeoxyuridine on cell division and differentiation of preimplantation mouse embryos.", "content": "Mouse embryos exposed to concentrations of 5-bromodeoxyuridine (BUdR) ranging from 0-01 to 1-0 mug/ml in vitro for two days from the 8-cell stage exhibit a concentration-dependent decrease in the frequency of normal blastocysts and decrease in average cell number per embryo. A 20-h exposure was adequate to achieve the full BUdR response. Both effects were eliminated in the presence of excess thymidine. Autoradiographs demonstrated that BUdR[3H] was incorporated into DNA during the first and second day of culture. Thus, BUdR appears to act through incorporation into DNA; and, in this system, cell division is at least as sensitive to BUdR as is differentiation.", "contents": "The effect of 5-bromodeoxyuridine on cell division and differentiation of preimplantation mouse embryos. Mouse embryos exposed to concentrations of 5-bromodeoxyuridine (BUdR) ranging from 0-01 to 1-0 mug/ml in vitro for two days from the 8-cell stage exhibit a concentration-dependent decrease in the frequency of normal blastocysts and decrease in average cell number per embryo. A 20-h exposure was adequate to achieve the full BUdR response. Both effects were eliminated in the presence of excess thymidine. Autoradiographs demonstrated that BUdR[3H] was incorporated into DNA during the first and second day of culture. Thus, BUdR appears to act through incorporation into DNA; and, in this system, cell division is at least as sensitive to BUdR as is differentiation."} {"id": "PMID:1270978", "title": "Complete preimplantation development in culture of parthenogenetic mouse embryos.", "content": "The present experiments were undertaken to determine whether, in parthenogenesis, heterozygous embryos develop better than homozygous embryos. Such experiments may provide an approach to elucidating whether fertilized embryos develop better than parthenogenetic ones because of heterozygosity, or if the sperm provides another contribution necessary for complete embryonic development. The parthenogenetic embryos studied included uniform haploids after extrusion of the second polar body, mosaic haploids in which each blastomere contained a genetically different haploid nucleus, and heterozygous diploid mouse embryos. Eggs were activated and cultured in a chemically defined medium. About three times as many mosaic haploid or heterozygous diploid eggs developed beyond the 4-cell stage after 98-100 h and to the blastocyst stage after 120 h in culture, than uniform haploid eggs. This indicates that the development of parthenogenetic embryos is probably under genetic control and that there was a better development of the heterozygous embryos. Mosaic haploid embryos showed the same high frequency of development as heterozygous diploids. The results therefore indicate that heterozygosity provided a developmental advantage even when distributed between two genetically different clones of cells in the same embryo.", "contents": "Complete preimplantation development in culture of parthenogenetic mouse embryos. The present experiments were undertaken to determine whether, in parthenogenesis, heterozygous embryos develop better than homozygous embryos. Such experiments may provide an approach to elucidating whether fertilized embryos develop better than parthenogenetic ones because of heterozygosity, or if the sperm provides another contribution necessary for complete embryonic development. The parthenogenetic embryos studied included uniform haploids after extrusion of the second polar body, mosaic haploids in which each blastomere contained a genetically different haploid nucleus, and heterozygous diploid mouse embryos. Eggs were activated and cultured in a chemically defined medium. About three times as many mosaic haploid or heterozygous diploid eggs developed beyond the 4-cell stage after 98-100 h and to the blastocyst stage after 120 h in culture, than uniform haploid eggs. This indicates that the development of parthenogenetic embryos is probably under genetic control and that there was a better development of the heterozygous embryos. Mosaic haploid embryos showed the same high frequency of development as heterozygous diploids. The results therefore indicate that heterozygosity provided a developmental advantage even when distributed between two genetically different clones of cells in the same embryo."} {"id": "PMID:1270979", "title": "Effects of formamide on neuroepithelial cells and on interkinetic nuclear migration in the chick embryo.", "content": "Young chicken embryos were incubated on media containing formamide at concentrations of 0-1, 0-25, 0-31, 0-37, 0-43 and 0-5 M. In the neuroepithelium of these embryos we found that (1) the 0-1 M concentration had no detectable effect, (2) the 0-25 M concentration only affected mitosis which was blocked in metaphase so that mitotic figures accumulated near the neurocoele, (3) 0-31 M formamide totally inhibited interkinetic nuclear migration and affected only slightly the cell asymmetry, (4) the 0-37 M concentration considerably reduced the amount of cytoplasmic microtubules and that the cells became round, (5) at 0-43 M formamide, all microtubules had disappeared and all cells were spherical, (6) 0-5 M formamide all cells were spherical, detached from one another and the epithelium had lost its usual characteristics. Our results on exposure of the cells to low temperature (2 degrees C) suggest that formamide directly affects microtubules. All the effects observed at concentrations up to 0-43 M formamide are reversible.", "contents": "Effects of formamide on neuroepithelial cells and on interkinetic nuclear migration in the chick embryo. Young chicken embryos were incubated on media containing formamide at concentrations of 0-1, 0-25, 0-31, 0-37, 0-43 and 0-5 M. In the neuroepithelium of these embryos we found that (1) the 0-1 M concentration had no detectable effect, (2) the 0-25 M concentration only affected mitosis which was blocked in metaphase so that mitotic figures accumulated near the neurocoele, (3) 0-31 M formamide totally inhibited interkinetic nuclear migration and affected only slightly the cell asymmetry, (4) the 0-37 M concentration considerably reduced the amount of cytoplasmic microtubules and that the cells became round, (5) at 0-43 M formamide, all microtubules had disappeared and all cells were spherical, (6) 0-5 M formamide all cells were spherical, detached from one another and the epithelium had lost its usual characteristics. Our results on exposure of the cells to low temperature (2 degrees C) suggest that formamide directly affects microtubules. All the effects observed at concentrations up to 0-43 M formamide are reversible."} {"id": "PMID:1270980", "title": "The teratogenic effects of hydrocortisone on palatal development in the hamster.", "content": "The effect of different doses of hydrocortisone, administered at various times during gestation, on the fetal hamster and its palatal development was studied. Both the frequency of cleft palate and that of resorption depended upon the dose of hydrocortisone and the time of its administration. Two peaks in the incidence of cleft palate were observed, which appeared to be due to inhibition of different events. Incidence of morphologically different types of cleft palate was related to the doses and gestational time of hydrocortisone treatment. A close association was observed between the frequency of cleft palate and fetal growth retardation and between the latter and the dose and time of drug administration. It was suggested that maternal physiology and the placental barrier may play a crucial role in cleft palate induction.", "contents": "The teratogenic effects of hydrocortisone on palatal development in the hamster. The effect of different doses of hydrocortisone, administered at various times during gestation, on the fetal hamster and its palatal development was studied. Both the frequency of cleft palate and that of resorption depended upon the dose of hydrocortisone and the time of its administration. Two peaks in the incidence of cleft palate were observed, which appeared to be due to inhibition of different events. Incidence of morphologically different types of cleft palate was related to the doses and gestational time of hydrocortisone treatment. A close association was observed between the frequency of cleft palate and fetal growth retardation and between the latter and the dose and time of drug administration. It was suggested that maternal physiology and the placental barrier may play a crucial role in cleft palate induction."} {"id": "PMID:1270981", "title": "Reorganization of retinotectal projection of compound eyes after various tectal lesions in Xenopus.", "content": "The retinotectal connexions of double nasal (NN), double temporal (TT) and double ventral (VV) eyes in juvenile Xenopus were mapped after post-metamorphic removal of the rostral, caudal, medial or lateral tectal halves with the subsequent cutting of the optic nerve of the operated eye. A whole visual field projection occurred from NN eyes on to residual caudal tectum, from TT eyes on to residual rostral tectum and from VV eyes on to residual medial tectum. When optic fibres from NN, TT or VV eyes grew into inappropriate rostral, caudal or lateral tectal halves respectively, there was a projection deficit in the nasal and temporal or in the dorsal and ventral poles of the visual field. The persisting scotomas in the visual field indicated that only the optic fibres of the central retinal fundus had succeeded in connecting with an inappropriate tectal half whereas the peripheral optic fibres had not. The incongruous results of optic nerve regeneration obtained in the various recombinations may be taken to indicate that the assumption of early embryonic pattern regulation is inadequate to explain the findings in this experimental situation.", "contents": "Reorganization of retinotectal projection of compound eyes after various tectal lesions in Xenopus. The retinotectal connexions of double nasal (NN), double temporal (TT) and double ventral (VV) eyes in juvenile Xenopus were mapped after post-metamorphic removal of the rostral, caudal, medial or lateral tectal halves with the subsequent cutting of the optic nerve of the operated eye. A whole visual field projection occurred from NN eyes on to residual caudal tectum, from TT eyes on to residual rostral tectum and from VV eyes on to residual medial tectum. When optic fibres from NN, TT or VV eyes grew into inappropriate rostral, caudal or lateral tectal halves respectively, there was a projection deficit in the nasal and temporal or in the dorsal and ventral poles of the visual field. The persisting scotomas in the visual field indicated that only the optic fibres of the central retinal fundus had succeeded in connecting with an inappropriate tectal half whereas the peripheral optic fibres had not. The incongruous results of optic nerve regeneration obtained in the various recombinations may be taken to indicate that the assumption of early embryonic pattern regulation is inadequate to explain the findings in this experimental situation."} {"id": "PMID:1270982", "title": "The distribution of melanocytes in the dorsal coats of a series of chimaeric mice.", "content": "Chimaeras, made by aggregating two embryos from the randomly-bred Q-strain, and X-inactivation mosaics both have similar, balanced distributions of pigmentation in the dorsal coat, while (C57BL X C3H) F1 reversible Recessive chimaeras tend to have an unbalanced pigment distribution, with a higher proportion of F1 pigmentation in the posterior than in the anterior part of the coat. This observation can be explained if differences in the timing of the migration of the two melanocyte populations from the neural crest cause anterior-posterior differences in selection pressures.", "contents": "The distribution of melanocytes in the dorsal coats of a series of chimaeric mice. Chimaeras, made by aggregating two embryos from the randomly-bred Q-strain, and X-inactivation mosaics both have similar, balanced distributions of pigmentation in the dorsal coat, while (C57BL X C3H) F1 reversible Recessive chimaeras tend to have an unbalanced pigment distribution, with a higher proportion of F1 pigmentation in the posterior than in the anterior part of the coat. This observation can be explained if differences in the timing of the migration of the two melanocyte populations from the neural crest cause anterior-posterior differences in selection pressures."} {"id": "PMID:1270983", "title": "Energetics of swimming of a sea turtle.", "content": "Young (mean mass 735 g) green turtles (Chelonia mydas) were able to swim in a water channel at sustained speeds between 0-14 and 0-35 m.s-1. Oxygen consumption at rest was was 0-07 l.kg-1.h-1; at maximum swimming speed oxygen consumption was 3-4 times greater than at rest for a given individual. In comparison with other animals of the same body mass the cost of transport for the green turtle (0.186lO2.kg-1.km-1) is less than that for flying birds but greater than that for fish. From drag measurements it was calculated that the aerobic efficiency of swimming was between 1 and 10%; the higher efficiencies were found at the higher swimming speeds. Based upon the drag calculations for young turtles, it is estimated that adult turtles making the round-trip breeding migration between Brazil and Ascension Island (4800 km) would require the equivalent of about 21% of their body mass in fat stores to account for the energetic cost of swimming.", "contents": "Energetics of swimming of a sea turtle. Young (mean mass 735 g) green turtles (Chelonia mydas) were able to swim in a water channel at sustained speeds between 0-14 and 0-35 m.s-1. Oxygen consumption at rest was was 0-07 l.kg-1.h-1; at maximum swimming speed oxygen consumption was 3-4 times greater than at rest for a given individual. In comparison with other animals of the same body mass the cost of transport for the green turtle (0.186lO2.kg-1.km-1) is less than that for flying birds but greater than that for fish. From drag measurements it was calculated that the aerobic efficiency of swimming was between 1 and 10%; the higher efficiencies were found at the higher swimming speeds. Based upon the drag calculations for young turtles, it is estimated that adult turtles making the round-trip breeding migration between Brazil and Ascension Island (4800 km) would require the equivalent of about 21% of their body mass in fat stores to account for the energetic cost of swimming."} {"id": "PMID:1270984", "title": "Insect blood-brain barrier: an electrophysiological investigation of its permeability to the aliphatic alcohols.", "content": "The anaesthetic effects of the aliphatic alcohols were used to measure their concentration at the neuronal surfaces of the cockroach central nervous system. The results were in most cases fairly closely described by first-order kinetics. The exchange half-times of the lower alcohols were only a few seconds, being little affected by the removal of the nerve sheath. The half-times for the higher alcohols were somewhat longer, and were more significantly reduced by desheathing; these observations were interpreted in terms of a reservoir effect resulting from their higher liposolubility. It was shown that the ionic diffusion barrier in intact nerve cords remained undamaged in the presence of the alcohols.", "contents": "Insect blood-brain barrier: an electrophysiological investigation of its permeability to the aliphatic alcohols. The anaesthetic effects of the aliphatic alcohols were used to measure their concentration at the neuronal surfaces of the cockroach central nervous system. The results were in most cases fairly closely described by first-order kinetics. The exchange half-times of the lower alcohols were only a few seconds, being little affected by the removal of the nerve sheath. The half-times for the higher alcohols were somewhat longer, and were more significantly reduced by desheathing; these observations were interpreted in terms of a reservoir effect resulting from their higher liposolubility. It was shown that the ionic diffusion barrier in intact nerve cords remained undamaged in the presence of the alcohols."} {"id": "PMID:1270985", "title": "Insect blood-brain barrier: a radioisotope study of the kinetics of exchange of a liposoluble molecule (n-butanol).", "content": "About 90% of the butanol uptake by the cockroach abdominal nerve cord washed out with half-times of a few seconds, in good agreement with an electrophysiological estimate, and the temperature sensitivity suggested an activation energy of 3 Kcal mole-1. The remaining activity washed out far more slowly, with a similar time course to that observed in a previous investigation which had not detected the fast fraction. Its size was similar to the non-volatile uptake, and was considerably affected by the butanol concentration and incubation period. It apparently consisted of butanol metabolites, which could be detected by chromatography.", "contents": "Insect blood-brain barrier: a radioisotope study of the kinetics of exchange of a liposoluble molecule (n-butanol). About 90% of the butanol uptake by the cockroach abdominal nerve cord washed out with half-times of a few seconds, in good agreement with an electrophysiological estimate, and the temperature sensitivity suggested an activation energy of 3 Kcal mole-1. The remaining activity washed out far more slowly, with a similar time course to that observed in a previous investigation which had not detected the fast fraction. Its size was similar to the non-volatile uptake, and was considerably affected by the butanol concentration and incubation period. It apparently consisted of butanol metabolites, which could be detected by chromatography."} {"id": "PMID:1270986", "title": "The action of the excretory apparatus of Calliphora vomitoria in handling injected sugar solution.", "content": "Recent evidence suggests that the isolated Malpighian tubules of Calliphora possess mechanisms which restrict the loss of glucose and trehalose from the insect. This report establishes that the intact, diuresing fly does not excrete glucose or trehalose when solutions of these sugars are injected. When solutions of non-metabolized sugars such as sorbose and xylose are injected into the fly, these sugars are rapidly excreted. High concentrations of sorbose and xylose are found in the urine, suggesting that rapid reabsorption of fluid occurs in the excretory apparatus even during the diuresis which the injections provoke. However, injected sucrose is apparently not excreted in large amounts and it is possible that the Malpighian tubules when functioning in vivo are impermeable to disaccharides.", "contents": "The action of the excretory apparatus of Calliphora vomitoria in handling injected sugar solution. Recent evidence suggests that the isolated Malpighian tubules of Calliphora possess mechanisms which restrict the loss of glucose and trehalose from the insect. This report establishes that the intact, diuresing fly does not excrete glucose or trehalose when solutions of these sugars are injected. When solutions of non-metabolized sugars such as sorbose and xylose are injected into the fly, these sugars are rapidly excreted. High concentrations of sorbose and xylose are found in the urine, suggesting that rapid reabsorption of fluid occurs in the excretory apparatus even during the diuresis which the injections provoke. However, injected sucrose is apparently not excreted in large amounts and it is possible that the Malpighian tubules when functioning in vivo are impermeable to disaccharides."} {"id": "PMID:1270987", "title": "The regulation of haemolymph calcium concentration of the crab Carcinus maenas (L.).", "content": "After acclimation, Carcinus can maintain calcium balance in dilute (35-100%) but not in low calcium sea water. 71% of total haemolymph calcium (9-54 +/- 0-42 mM) was in ionic form as compared with 90-9%(9-9mM) in sea water. On acclimation to dilute sea water the calcium activity of the haemolymph was greater than that of the medium, the difference being maintained by active calcium uptake. Carcinus is highly permeable to Ca2+, influx from sea water being 0-513 +/- 0-07 mumoles g-1 h-1 and the time constant for calcium influx 4-3 +/- 0-48 h. Calcium space represented ca. 25% wet body weight independent of body size or salinity of acclimation medium.", "contents": "The regulation of haemolymph calcium concentration of the crab Carcinus maenas (L.). After acclimation, Carcinus can maintain calcium balance in dilute (35-100%) but not in low calcium sea water. 71% of total haemolymph calcium (9-54 +/- 0-42 mM) was in ionic form as compared with 90-9%(9-9mM) in sea water. On acclimation to dilute sea water the calcium activity of the haemolymph was greater than that of the medium, the difference being maintained by active calcium uptake. Carcinus is highly permeable to Ca2+, influx from sea water being 0-513 +/- 0-07 mumoles g-1 h-1 and the time constant for calcium influx 4-3 +/- 0-48 h. Calcium space represented ca. 25% wet body weight independent of body size or salinity of acclimation medium."} {"id": "PMID:1270988", "title": "Form of developing bends in reactivated sperm flagella.", "content": "1. Dark-field, multiple-exposure photographs of reactivated tritonated sea urchin sperm flagella swimming under a variety of conditions were analysed. 2. The length, radius and subtended angle of bends increased during bend development. The pattern of development was essentially the same under all conditions observed. 3. The angles of the two bends nearest the base tend to increase at the same rate, cancelling one another, so that the development of new bends causes little if any net microtubular sliding. 4. The direction of microtubular sliding within a bend is initially in the same direction as that within the preceding bend, and reverses as the bend develops.", "contents": "Form of developing bends in reactivated sperm flagella. 1. Dark-field, multiple-exposure photographs of reactivated tritonated sea urchin sperm flagella swimming under a variety of conditions were analysed. 2. The length, radius and subtended angle of bends increased during bend development. The pattern of development was essentially the same under all conditions observed. 3. The angles of the two bends nearest the base tend to increase at the same rate, cancelling one another, so that the development of new bends causes little if any net microtubular sliding. 4. The direction of microtubular sliding within a bend is initially in the same direction as that within the preceding bend, and reverses as the bend develops."} {"id": "PMID:1270989", "title": "The receptive fields of Daphnia ommatidia.", "content": "1. The focal length and positions of the principal planes of an isolated Daphnia lens were determined, and the refractive index of the rhabdom was measured. 2. The lens can form an image, but this always lies well behind the rhabdom. This was confirmed by direct observation of images inside a clear-eye mutant Daphnia eye. 3. The rhabdom was shown to be unlikely to function as a waveguide, and a ray optics model is proposed to enable the prediction of ommatidial receptive fields from the lens data. 4. The predicted receptive fields have wide plateaus and steep sides, and there are virtually no totally blind gaps between neighbouring ommatidia.", "contents": "The receptive fields of Daphnia ommatidia. 1. The focal length and positions of the principal planes of an isolated Daphnia lens were determined, and the refractive index of the rhabdom was measured. 2. The lens can form an image, but this always lies well behind the rhabdom. This was confirmed by direct observation of images inside a clear-eye mutant Daphnia eye. 3. The rhabdom was shown to be unlikely to function as a waveguide, and a ray optics model is proposed to enable the prediction of ommatidial receptive fields from the lens data. 4. The predicted receptive fields have wide plateaus and steep sides, and there are virtually no totally blind gaps between neighbouring ommatidia."} {"id": "PMID:1270990", "title": "Sodium extrusion by the sea-water-acclimated fiddler crab Uca pugilator: comparison with other marine crustacea and marine teleost fish.", "content": "1. Measurements of the blood Na concentration and transepithelial electrical potential (T.E.P.) across Uca pugilator acclimated to sea water indicate that Na is maintained out of electrochemical equilibrium with sea water. The resulting net Na influx as well as the sodium gain due to ingestion of the medium must be balanced by extrarenal Na extrusion. 2. The small T.E.P. (-0.7 mV) and the 'transport numbers' of Na and Cl indicate that the permeability to these ions is equivalent. 3. Removal of external K results in a significant stimulation of unidirectional Na efflux that is dependent upon external Na but is not inhibited by ouabain. 4. Transfer of Uca to K and Na-free sea water results in a 54% decline in unidirectional efflux, which is not due to T.E.P. changes. Readdition of 25mM-K stimulates Na efflux much more than can be accounted for by changes in the T.E.P. Readdition of 25mM-Na to potassium-free sea water does not change the Na efflux. 5. The results indicate that Na extrusion by Uca is via a Na/K exchange mechanism which partially inhibits Na/Na exchange. Cessation of Na/K exchange (in K-free sea water) removes this inhibition and allows rapid Na/Na exchange. It is not known whether Na/K and Na/Na exchange are via the same or parallel carrier systems.", "contents": "Sodium extrusion by the sea-water-acclimated fiddler crab Uca pugilator: comparison with other marine crustacea and marine teleost fish. 1. Measurements of the blood Na concentration and transepithelial electrical potential (T.E.P.) across Uca pugilator acclimated to sea water indicate that Na is maintained out of electrochemical equilibrium with sea water. The resulting net Na influx as well as the sodium gain due to ingestion of the medium must be balanced by extrarenal Na extrusion. 2. The small T.E.P. (-0.7 mV) and the 'transport numbers' of Na and Cl indicate that the permeability to these ions is equivalent. 3. Removal of external K results in a significant stimulation of unidirectional Na efflux that is dependent upon external Na but is not inhibited by ouabain. 4. Transfer of Uca to K and Na-free sea water results in a 54% decline in unidirectional efflux, which is not due to T.E.P. changes. Readdition of 25mM-K stimulates Na efflux much more than can be accounted for by changes in the T.E.P. Readdition of 25mM-Na to potassium-free sea water does not change the Na efflux. 5. The results indicate that Na extrusion by Uca is via a Na/K exchange mechanism which partially inhibits Na/Na exchange. Cessation of Na/K exchange (in K-free sea water) removes this inhibition and allows rapid Na/Na exchange. It is not known whether Na/K and Na/Na exchange are via the same or parallel carrier systems."} {"id": "PMID:1270991", "title": "The effects of hypophysectomy, prolactin therapy and environmental calcium on electrolyte balance of the brown trout Salmo trutta, L.", "content": "Adaptation of the brown trout to fresh water containing increasing concentrations of calcium resulted in a decrease in plasma electrolyte level and total electrolyte excretion. The electrolyte excretion rate was higher at the beginning than at the end of the urine collection periods. Hypophysectomized fish had a lower plasma electrolyte concentration than the controls. This deficiency was partially corrected by polactin therapy. High environmental calcium was only effective to a limited extent. There was no difference in the normal renal sodium output between hypophysectomized and intact fish in fresh water. Environmental calcium did not have any significant effect on renal electrolyte output of hypophysectomized fish.", "contents": "The effects of hypophysectomy, prolactin therapy and environmental calcium on electrolyte balance of the brown trout Salmo trutta, L. Adaptation of the brown trout to fresh water containing increasing concentrations of calcium resulted in a decrease in plasma electrolyte level and total electrolyte excretion. The electrolyte excretion rate was higher at the beginning than at the end of the urine collection periods. Hypophysectomized fish had a lower plasma electrolyte concentration than the controls. This deficiency was partially corrected by polactin therapy. High environmental calcium was only effective to a limited extent. There was no difference in the normal renal sodium output between hypophysectomized and intact fish in fresh water. Environmental calcium did not have any significant effect on renal electrolyte output of hypophysectomized fish."} {"id": "PMID:1270992", "title": "Properties of the trochanteral hair plate and its function in the control of walking in the cockroach.", "content": "1. The physiological properties of the group of long hair sensilla of the trochanteral hair plate in the cockroach metathoracic leg were studied. The sensilla were divided into type I and type II according to their responses to imposed displacements. 2. Type I hair sensilla responded to dynamic displacements whereas type II hair sensilla responded to both dynamic and static displacements. The hair sensilla are normally excited by phasic flexion movements of the femur near the end of leg protraction. 3. Activity in the trochanteral hair plate afferents had a short latency excitatory effect on the motoneurone producing slow extension movements of the femur and an inhibitory effect on the femur flexor motoneurones. 4. Removal of the trochanteral hair plate in one leg caused overstepping of that leg in a walking animal due to exaggerated flexion of the femur. This change in leg movement can be explained by the removal of the inhibitory influence from the hair plate afferents to the femur flexor motoneurones. 5. We conclude that one function of the trochanteral hair plate is to limit femur flexion during a step cycle.", "contents": "Properties of the trochanteral hair plate and its function in the control of walking in the cockroach. 1. The physiological properties of the group of long hair sensilla of the trochanteral hair plate in the cockroach metathoracic leg were studied. The sensilla were divided into type I and type II according to their responses to imposed displacements. 2. Type I hair sensilla responded to dynamic displacements whereas type II hair sensilla responded to both dynamic and static displacements. The hair sensilla are normally excited by phasic flexion movements of the femur near the end of leg protraction. 3. Activity in the trochanteral hair plate afferents had a short latency excitatory effect on the motoneurone producing slow extension movements of the femur and an inhibitory effect on the femur flexor motoneurones. 4. Removal of the trochanteral hair plate in one leg caused overstepping of that leg in a walking animal due to exaggerated flexion of the femur. This change in leg movement can be explained by the removal of the inhibitory influence from the hair plate afferents to the femur flexor motoneurones. 5. We conclude that one function of the trochanteral hair plate is to limit femur flexion during a step cycle."} {"id": "PMID:1270993", "title": "Printed circuit microelectrodes and their application to honeybee brain.", "content": "The application of printed circuit technology to the production of a new type of multi-channel microelectrode is described. 2. Recordings have been obtained from the the protocerebrum of the honeybee Apis mellifera L. using printed circuit microelectrodes in both restrained and free-moving preparations. 3. These recordings are compared with those previously obtained from conventional probe microelectrodes and are found to have similar characteristics of transient voltage changes superimposed on an undifferentiated high frequency background. 4. A wide range of development possibilities for the printed circuit microelectrode are discussed.", "contents": "Printed circuit microelectrodes and their application to honeybee brain. The application of printed circuit technology to the production of a new type of multi-channel microelectrode is described. 2. Recordings have been obtained from the the protocerebrum of the honeybee Apis mellifera L. using printed circuit microelectrodes in both restrained and free-moving preparations. 3. These recordings are compared with those previously obtained from conventional probe microelectrodes and are found to have similar characteristics of transient voltage changes superimposed on an undifferentiated high frequency background. 4. A wide range of development possibilities for the printed circuit microelectrode are discussed."} {"id": "PMID:1270994", "title": "Carbon dioxide combining properties of the blood of the shore crab Carcinus maenas (L): carbon dioxide solubility coefficient and carbonic acid dissociation constants.", "content": "The carbon dioxide solubility coefficient, alphaCO2, and the apparent carbonic acid dissociation constants, K'1 and K'2 were estimated in the serum of the crab Carcinus maenas at various temperatures and ionic strengths. At 15 degrees C, the indirectly determined alphaCO2 value is 0-0499 m-mole l-1 torr-1 for crabs living in normal sea water (salinity ca. 35 percent). It is apparently independent of the serum protein concentration and of the stage of the moulting cycle. For crabs living in undiluted sea water, the mean pK'1 value, determined either gasometrically or titrimetrically, is 6-027 at 15 degrees C. At the same temperature, pK'2=9-29. These values approximate to those of sea water at 35 percent salinity. pK'1 drops as temperature rises; the measured deltapK'1/deltat is -0-0053 pH unit degrees C-1 between 10 and 30 degrees C. PK'1 rises as the ionic strength is lowered. Alignment nomograms have been constructed for the determination of alphaCO2, pK'1 and pK'2 values in relation to various conditions of temperature and salinity.", "contents": "Carbon dioxide combining properties of the blood of the shore crab Carcinus maenas (L): carbon dioxide solubility coefficient and carbonic acid dissociation constants. The carbon dioxide solubility coefficient, alphaCO2, and the apparent carbonic acid dissociation constants, K'1 and K'2 were estimated in the serum of the crab Carcinus maenas at various temperatures and ionic strengths. At 15 degrees C, the indirectly determined alphaCO2 value is 0-0499 m-mole l-1 torr-1 for crabs living in normal sea water (salinity ca. 35 percent). It is apparently independent of the serum protein concentration and of the stage of the moulting cycle. For crabs living in undiluted sea water, the mean pK'1 value, determined either gasometrically or titrimetrically, is 6-027 at 15 degrees C. At the same temperature, pK'2=9-29. These values approximate to those of sea water at 35 percent salinity. pK'1 drops as temperature rises; the measured deltapK'1/deltat is -0-0053 pH unit degrees C-1 between 10 and 30 degrees C. PK'1 rises as the ionic strength is lowered. Alignment nomograms have been constructed for the determination of alphaCO2, pK'1 and pK'2 values in relation to various conditions of temperature and salinity."} {"id": "PMID:1270995", "title": "Contribution of an electrogenic pump to the resting membrane polarization in a crustacean heart.", "content": "1. In the neurogenic heart of the isopod crustacean Porcellio dilatatus, external K+ removal depolarized the membrane (K0 effect) whereas subsequent restoration of K+ resulted in a rapid hyperpolarization (K1 effect). 2. The amplitude of the K1 effect depended on the duration of the prior K+ deprivation and on the subsequent K+ concentration. 3. The membrane resistance slightly increased during the K0 effect; during the K1 effect, it only returned to its control value. 4. Ouabain, cooling and replacement of external Na+ by Li+ also produced depolarization. 5. The K1 effect was suppressed by ouabain and markedly depressed by lowering the temperature to 4-6 degrees C. It was abolished if Li+ replaced Na+ during the prior privation of K+; moreover Li+ was unable to act as a substitute for external K+ in generating the K1 effect if used at equivalent concentration, but enhanced the effect at high concentration. 6. The findings are consistent with the presence of an electrogenic sodium pump in the myocardium of Porcellio contributing to the resting membrane potential. 7. Changes in the spontaneous rhythm observed during K0 and K1 are further suggestive of the presence of an electrogenic Na+ pump in the pacemaker neurons of the cardiac ganglion. Another explanation is also proposed. 8. The magnitude of the spontaneous contractions of the heart was increased during the K0 effect and markedly decreased during the K1 effect. An indirect effect of the changes in internal Na+ concentration on the contractile processes is suggested.", "contents": "Contribution of an electrogenic pump to the resting membrane polarization in a crustacean heart. 1. In the neurogenic heart of the isopod crustacean Porcellio dilatatus, external K+ removal depolarized the membrane (K0 effect) whereas subsequent restoration of K+ resulted in a rapid hyperpolarization (K1 effect). 2. The amplitude of the K1 effect depended on the duration of the prior K+ deprivation and on the subsequent K+ concentration. 3. The membrane resistance slightly increased during the K0 effect; during the K1 effect, it only returned to its control value. 4. Ouabain, cooling and replacement of external Na+ by Li+ also produced depolarization. 5. The K1 effect was suppressed by ouabain and markedly depressed by lowering the temperature to 4-6 degrees C. It was abolished if Li+ replaced Na+ during the prior privation of K+; moreover Li+ was unable to act as a substitute for external K+ in generating the K1 effect if used at equivalent concentration, but enhanced the effect at high concentration. 6. The findings are consistent with the presence of an electrogenic sodium pump in the myocardium of Porcellio contributing to the resting membrane potential. 7. Changes in the spontaneous rhythm observed during K0 and K1 are further suggestive of the presence of an electrogenic Na+ pump in the pacemaker neurons of the cardiac ganglion. Another explanation is also proposed. 8. The magnitude of the spontaneous contractions of the heart was increased during the K0 effect and markedly decreased during the K1 effect. An indirect effect of the changes in internal Na+ concentration on the contractile processes is suggested."} {"id": "PMID:1270996", "title": "Unidirectional ion movements in the hindgut of larval Sarcophaga bullata (Diptera: Sarcophagidae).", "content": "1. Unidirectional Na+, K+, and Cl- fluxes were measured across the isolated hindgut of larval Sarcophaga bullata. 2. Both K+ and Cl- are actively secreted into the hindgut lumen, whereas Na+ is distributed passively. 3. The movements of K+ and Cl- are not entirely independent of each other, and the movement of one ion influences the flux of the co-ion. 4. The NH4+ ion is secreted into the hindgut by a mechanism separate from K+ secretion.", "contents": "Unidirectional ion movements in the hindgut of larval Sarcophaga bullata (Diptera: Sarcophagidae). 1. Unidirectional Na+, K+, and Cl- fluxes were measured across the isolated hindgut of larval Sarcophaga bullata. 2. Both K+ and Cl- are actively secreted into the hindgut lumen, whereas Na+ is distributed passively. 3. The movements of K+ and Cl- are not entirely independent of each other, and the movement of one ion influences the flux of the co-ion. 4. The NH4+ ion is secreted into the hindgut by a mechanism separate from K+ secretion."} {"id": "PMID:1271011", "title": "Effect of recent antigen priming on adoptive immune responses. IV. Antigen-induced selective recruitment of recirculating lymphocytes to the spleen demonstrable with a microculture system.", "content": "When thoracic duct lymphocytes (TDL) from mice given sheep erythrocytes (SRC) 1 day previously (1-day-primed TDL) were placed in microcultures with antigen for 5-6 days, the cells failed to produce antibody to SRC, but responded well to horse erythrocytes (HRC); reciprocal results were obtained with TDL from HRC-injected mice. The specific unresponsiveness of the TDL was observed despite the presence of an allogeneic factor in the cultures; this factor exerted not only a macrophage-like effect (TDL from normal mice failed to respond in the absence of this factor) but also a T-cell-replacing function. It was concluded therefore that the unresponsiveness of the TDL was the result of selective recruitment of specific B lymphocyte precursors from the recirculating lymphocyte pool to the lymphoid tissues; whether there was also recruitment of specific T lymphocytes was not investigated. Since addition of 1-day-primed TDL to cultures of normal TDL did not inhibit the response of the latter, there was no evidence that active suppression accounted for the unresponsiveness. The spleen appeared to be the main site for recruitment since 1-day-primed spleen cells placed in microcultures contained above normal numbers of specifically-reactive precursors. This was in striking contrast to the effect of transferring 1-day-primed spleen cells in vivo where, as previously reported, the cells fail to respond to the injected antigen within 1 wk of transfer. An explanation for this paradox is discussed.", "contents": "Effect of recent antigen priming on adoptive immune responses. IV. Antigen-induced selective recruitment of recirculating lymphocytes to the spleen demonstrable with a microculture system. When thoracic duct lymphocytes (TDL) from mice given sheep erythrocytes (SRC) 1 day previously (1-day-primed TDL) were placed in microcultures with antigen for 5-6 days, the cells failed to produce antibody to SRC, but responded well to horse erythrocytes (HRC); reciprocal results were obtained with TDL from HRC-injected mice. The specific unresponsiveness of the TDL was observed despite the presence of an allogeneic factor in the cultures; this factor exerted not only a macrophage-like effect (TDL from normal mice failed to respond in the absence of this factor) but also a T-cell-replacing function. It was concluded therefore that the unresponsiveness of the TDL was the result of selective recruitment of specific B lymphocyte precursors from the recirculating lymphocyte pool to the lymphoid tissues; whether there was also recruitment of specific T lymphocytes was not investigated. Since addition of 1-day-primed TDL to cultures of normal TDL did not inhibit the response of the latter, there was no evidence that active suppression accounted for the unresponsiveness. The spleen appeared to be the main site for recruitment since 1-day-primed spleen cells placed in microcultures contained above normal numbers of specifically-reactive precursors. This was in striking contrast to the effect of transferring 1-day-primed spleen cells in vivo where, as previously reported, the cells fail to respond to the injected antigen within 1 wk of transfer. An explanation for this paradox is discussed."} {"id": "PMID:1271012", "title": "Collagen-and collagen peptide-induced chemotaxis of human blood monocytes.", "content": "The ability of collagen and collagen-derived peptides to act as chemotactic stimuli was investigated by in vitro chemotaxis assays. Native human and chick skin collagen (type I) and alpha-chains obtained from purified chick skin collagen were each chemotactic for human peripheral blood monocytes. In addition, smaller peptides obtained either by digesting native collagen with bacterial collagenase or by degrading purified alpha-chains with cyanogen bromide or pepsin were also chemotactic for monocytes. In contrast, native collagen, alpha-chains, and smaller collagen-derived peptides were not chemotactic for human neutrophils. Since collagen is degraded at sites of tissue damage and inflammation, our findings suggest the possibility that such collagen-derived degradation products might directly serve as chemotactic stimuli for human peripheral blood monocytes in vivo.", "contents": "Collagen-and collagen peptide-induced chemotaxis of human blood monocytes. The ability of collagen and collagen-derived peptides to act as chemotactic stimuli was investigated by in vitro chemotaxis assays. Native human and chick skin collagen (type I) and alpha-chains obtained from purified chick skin collagen were each chemotactic for human peripheral blood monocytes. In addition, smaller peptides obtained either by digesting native collagen with bacterial collagenase or by degrading purified alpha-chains with cyanogen bromide or pepsin were also chemotactic for monocytes. In contrast, native collagen, alpha-chains, and smaller collagen-derived peptides were not chemotactic for human neutrophils. Since collagen is degraded at sites of tissue damage and inflammation, our findings suggest the possibility that such collagen-derived degradation products might directly serve as chemotactic stimuli for human peripheral blood monocytes in vivo."} {"id": "PMID:1271013", "title": "Successful treatment of enterovirus-infected mice by 2-(alpha-hydroxybenzyl)-benzimidazole and guanidine.", "content": "Echo virus 9- or Coxsackie A 9-infected newborn mice are protected from paralysis and death by combined treatment with nontoxic concentrations of HBB plus guanidine. HBB alone also protects Coxsackie A 9, but not echo virus 9-infected animals, whereas guanidine alone is ineffective in either case. Protection is due to inhibition of virus multiplication via the antiviral activity of these selective inhibitors. Treatment must be begun at the latest 48 h after virus inoculation. 3 days of treatment are sufficient if started at the time of virus inoculation. Failure of protection after treatment with one compound alone is not due to rapid development of drug-resistant virus mutants. Infected, successfully treated mice may develop a solid immunity.", "contents": "Successful treatment of enterovirus-infected mice by 2-(alpha-hydroxybenzyl)-benzimidazole and guanidine. Echo virus 9- or Coxsackie A 9-infected newborn mice are protected from paralysis and death by combined treatment with nontoxic concentrations of HBB plus guanidine. HBB alone also protects Coxsackie A 9, but not echo virus 9-infected animals, whereas guanidine alone is ineffective in either case. Protection is due to inhibition of virus multiplication via the antiviral activity of these selective inhibitors. Treatment must be begun at the latest 48 h after virus inoculation. 3 days of treatment are sufficient if started at the time of virus inoculation. Failure of protection after treatment with one compound alone is not due to rapid development of drug-resistant virus mutants. Infected, successfully treated mice may develop a solid immunity."} {"id": "PMID:1271014", "title": "Introduction of B-chain-inactivated ricin into mouse macrophages and rat Kupffer cells via their membrane Fc receptors.", "content": "Experiments have been made to test whether the toxic lectin ricin can be bound to and introduced into cells by some other mechanism than via its B chain, the natural binding moiety of the toxin, without its toxic effect being neutralized. Complexes consisting of ricin and antibodies specifically directed against ricin B chain were incubated with mouse peritoneal macrophages and rat Kupffer cells, which are known to possess surface receptors for the Fc portion of the immunoglobulin molecule. After incubation for 26 h, cellular protein synthesis, as measured by incorporation of labeled leucine into acid-insoluble material, was completely inhibited. HeLa cells, which do not possess Fc receptors, were unaffected by the complex. The effect of the complex on protein synthesis of macrophages was prevented by soluble antigen-antibody complexes, but not by the presence of lactose which prevents attachment of the ricin B chain to the cell membrane. The [ricin-antiricin B] complex was attached to red cells, and the resulting complex was incubated with rat Kupffer cells. Cellular protein synthesis ceased after 6 h, and phase contrast microscopy studies showed that the complexes were taken up by the Kupffer cells. The data indicate that ricin, when present in the complex with antiricin B, can be introduced into cells through cell membrane receptors other than the B chain receptor, in this case the Fc receptor, and that the internalized toxin retains a least part of its activity.", "contents": "Introduction of B-chain-inactivated ricin into mouse macrophages and rat Kupffer cells via their membrane Fc receptors. Experiments have been made to test whether the toxic lectin ricin can be bound to and introduced into cells by some other mechanism than via its B chain, the natural binding moiety of the toxin, without its toxic effect being neutralized. Complexes consisting of ricin and antibodies specifically directed against ricin B chain were incubated with mouse peritoneal macrophages and rat Kupffer cells, which are known to possess surface receptors for the Fc portion of the immunoglobulin molecule. After incubation for 26 h, cellular protein synthesis, as measured by incorporation of labeled leucine into acid-insoluble material, was completely inhibited. HeLa cells, which do not possess Fc receptors, were unaffected by the complex. The effect of the complex on protein synthesis of macrophages was prevented by soluble antigen-antibody complexes, but not by the presence of lactose which prevents attachment of the ricin B chain to the cell membrane. The [ricin-antiricin B] complex was attached to red cells, and the resulting complex was incubated with rat Kupffer cells. Cellular protein synthesis ceased after 6 h, and phase contrast microscopy studies showed that the complexes were taken up by the Kupffer cells. The data indicate that ricin, when present in the complex with antiricin B, can be introduced into cells through cell membrane receptors other than the B chain receptor, in this case the Fc receptor, and that the internalized toxin retains a least part of its activity."} {"id": "PMID:1271015", "title": "Simultaneous and backward fear conditioning as a function of number of CS-UCS pairings.", "content": "Four experiments examined the possibility that the outcome of simultaneous and backward fear conditioning procedures might depend upon the number of CS-UCS pairings. A punishment procedure will rats as subjects and shock as the UCS was used; the amount of suppression produced by response-contingent CS presentations indexed the strength of acquired fear. Experiments 1, 3, and 4 examined the suppressive tendencies of simultaneous-and backward-trained CSs after 0, 10, 20, 40, 80, and 160 pairings. The pattern of data suggested that initial pairings have the effect of increasing suppressive tendencies of the CS, while subsequent pairings decrease them. In addition, evidence of fear inhibition was found after 160 pairings in the case of the backward paradigm. Experiment 2 examined several nonassociative accounts based upon differential shock exposure. Groups given 10 pairings or 80 pairings were compared to ggroups given 10 pairings plus 70 shock-alone presentations. The results indicated that number of pairings, rather than number of UCS occurrences, is the important factor in decreasing the initial suppression. The evidence for eventual inhibition in the backward paradigm suggests that this occurs through the acquisition of inhibitory tendencies which are antagonistic to the previously conditioned excitation.", "contents": "Simultaneous and backward fear conditioning as a function of number of CS-UCS pairings. Four experiments examined the possibility that the outcome of simultaneous and backward fear conditioning procedures might depend upon the number of CS-UCS pairings. A punishment procedure will rats as subjects and shock as the UCS was used; the amount of suppression produced by response-contingent CS presentations indexed the strength of acquired fear. Experiments 1, 3, and 4 examined the suppressive tendencies of simultaneous-and backward-trained CSs after 0, 10, 20, 40, 80, and 160 pairings. The pattern of data suggested that initial pairings have the effect of increasing suppressive tendencies of the CS, while subsequent pairings decrease them. In addition, evidence of fear inhibition was found after 160 pairings in the case of the backward paradigm. Experiment 2 examined several nonassociative accounts based upon differential shock exposure. Groups given 10 pairings or 80 pairings were compared to ggroups given 10 pairings plus 70 shock-alone presentations. The results indicated that number of pairings, rather than number of UCS occurrences, is the important factor in decreasing the initial suppression. The evidence for eventual inhibition in the backward paradigm suggests that this occurs through the acquisition of inhibitory tendencies which are antagonistic to the previously conditioned excitation."} {"id": "PMID:1271016", "title": "Unconditional stimulus characteristics in rabbit eyelid conditioning.", "content": "Three experiments employed aversive or positive subcortical electrical stimulation in an unconditional stimulus (US) role in rabbit eyelid conditioning. Conditional response (CR) development to a tonal conditional stimulus (CS) was examined when the intracranial stimulation was combined with a conventional cheek-shock US (Experiment 1) or with a lightflash US (Experiment 2). Our findings were consistent with previus observations that the affective impact of the US is important in the development of an overt motor CR. The complex pattern of our results, however, implies that intracranial stimulation has multiple effects on conditioning and argues against any unidimensional interpretation of these outcomes. Our analysis of CR-contingent intracranial stimulation presentation in Experiment 3 indicated that such stimulation does not act as a Thorndikian reward or punishment in rabbit eyelid conditioning.", "contents": "Unconditional stimulus characteristics in rabbit eyelid conditioning. Three experiments employed aversive or positive subcortical electrical stimulation in an unconditional stimulus (US) role in rabbit eyelid conditioning. Conditional response (CR) development to a tonal conditional stimulus (CS) was examined when the intracranial stimulation was combined with a conventional cheek-shock US (Experiment 1) or with a lightflash US (Experiment 2). Our findings were consistent with previus observations that the affective impact of the US is important in the development of an overt motor CR. The complex pattern of our results, however, implies that intracranial stimulation has multiple effects on conditioning and argues against any unidimensional interpretation of these outcomes. Our analysis of CR-contingent intracranial stimulation presentation in Experiment 3 indicated that such stimulation does not act as a Thorndikian reward or punishment in rabbit eyelid conditioning."} {"id": "PMID:1271017", "title": "The reliability of a mechanized procedure (Perkin-Elmer C4) for the Enzymatic determination of uric acid according to Kageyama.", "content": "The enzymatic determination of the uric acie concentration in urine and serum according to Kageyama ((1971), Clin. Chim. Acta 31, 421--426), which excludes the deproteinization of samples, was adapted to the C4 automatic analyzer (Perkin-Elmer). The reliability of this procedure and its correlation with an UV-method were investigated. The interaction from-sample-to-sample was considerable, but this could be reduced by the addition of Brij-35. The recovery of uric acid added to protein-containing samples (about 96%) was better than with the UV-method. Novaminsulfone was the only substance tested which interfered significantly.", "contents": "The reliability of a mechanized procedure (Perkin-Elmer C4) for the Enzymatic determination of uric acid according to Kageyama. The enzymatic determination of the uric acie concentration in urine and serum according to Kageyama ((1971), Clin. Chim. Acta 31, 421--426), which excludes the deproteinization of samples, was adapted to the C4 automatic analyzer (Perkin-Elmer). The reliability of this procedure and its correlation with an UV-method were investigated. The interaction from-sample-to-sample was considerable, but this could be reduced by the addition of Brij-35. The recovery of uric acid added to protein-containing samples (about 96%) was better than with the UV-method. Novaminsulfone was the only substance tested which interfered significantly."} {"id": "PMID:1271018", "title": "The influence of D-penicillamine on enzymatic activities: glucose-6-phosphate dehydrogenase. Correlation with serum levels measured in humans.", "content": "The influence of D-penicillamine on glucose-6-phosphate dehydrogenase of yeast (pure enzyme), human hemolysate, and human skin homogenate were determined. In high concentrations, D-penicillamine inhibits glucose-6-phosphate dehydrogenase activity (concentrations above 6.7 mmol/l, i. e. l g/l). In low concentrations, D-penicilliamine exerts an indirect influence by removing some inhibiting metal ions, such as zinc. In human skin homogenates, an activating action of D-penicillamine on glucose-6-phosphate dehydrogenase activity occurs due to the chelation of metal ions.", "contents": "The influence of D-penicillamine on enzymatic activities: glucose-6-phosphate dehydrogenase. Correlation with serum levels measured in humans. The influence of D-penicillamine on glucose-6-phosphate dehydrogenase of yeast (pure enzyme), human hemolysate, and human skin homogenate were determined. In high concentrations, D-penicillamine inhibits glucose-6-phosphate dehydrogenase activity (concentrations above 6.7 mmol/l, i. e. l g/l). In low concentrations, D-penicilliamine exerts an indirect influence by removing some inhibiting metal ions, such as zinc. In human skin homogenates, an activating action of D-penicillamine on glucose-6-phosphate dehydrogenase activity occurs due to the chelation of metal ions."} {"id": "PMID:1271019", "title": "[Determination of lead in beard hair by atomic absorption spectrometry (author's transl)].", "content": "The lead content of hair from the electric razor can be determined by atomic absorption spectrometry, using the micro-sampling technique of Delves. 1--5 mg of the washed and dried hair are partially oxidized with hydrogen peroxide prior to analysis. The method is simple and quick and therefore suited for the serial investigation of persons exposed to lead.", "contents": "[Determination of lead in beard hair by atomic absorption spectrometry (author's transl)]. The lead content of hair from the electric razor can be determined by atomic absorption spectrometry, using the micro-sampling technique of Delves. 1--5 mg of the washed and dried hair are partially oxidized with hydrogen peroxide prior to analysis. The method is simple and quick and therefore suited for the serial investigation of persons exposed to lead."} {"id": "PMID:1271020", "title": "[Protection of erythrocytes in D2O against damage by hyperthermy and freezing (author's transl)].", "content": "The haemolysis of erythrocytes after heating to 55 degrees C, after freezing and after osmotic damage was studied in normal water and in heavy water (D2O). Haemolysis in all cases was lower in the presence of D2O. The greatest increase in stability was observed between 5--20% D2O. The practical consequences of this protective effect for the preservation of blood are discussed.", "contents": "[Protection of erythrocytes in D2O against damage by hyperthermy and freezing (author's transl)]. The haemolysis of erythrocytes after heating to 55 degrees C, after freezing and after osmotic damage was studied in normal water and in heavy water (D2O). Haemolysis in all cases was lower in the presence of D2O. The greatest increase in stability was observed between 5--20% D2O. The practical consequences of this protective effect for the preservation of blood are discussed."} {"id": "PMID:1271021", "title": "[Micromethod for the determination of glucose with glucose dehydrogenase in the autoanalyzer (author's transl)].", "content": "A new AutoAnalyzer method is described for the determination of glucose in 20 mul of haemolysate, urine, or cerebrospinal fluid, using glucose dehydrogenase. Without loss of precision, accuracy, sensitivity, or linearity, 900 samples may be analyzed, using the same volume of reagents normally required for the manual analysis of 75 samples. A comparison with the hexokinase method yields a correlation of 0.9978. A haemolysing solution compatible with the reagents used is described.", "contents": "[Micromethod for the determination of glucose with glucose dehydrogenase in the autoanalyzer (author's transl)]. A new AutoAnalyzer method is described for the determination of glucose in 20 mul of haemolysate, urine, or cerebrospinal fluid, using glucose dehydrogenase. Without loss of precision, accuracy, sensitivity, or linearity, 900 samples may be analyzed, using the same volume of reagents normally required for the manual analysis of 75 samples. A comparison with the hexokinase method yields a correlation of 0.9978. A haemolysing solution compatible with the reagents used is described."} {"id": "PMID:1271022", "title": "Are more items identified than can be reported?", "content": "Subjects are typically able to report only about four items from a many-item array presented tachistoscopically (full-report span). Current models of visual information processing disagree as to whether the limiting process is best represented as identification or as short-term memory. Estes and Taylor have argued that the number of items identified is up to twice the full-report span and, hence, that memory limits report. Experiment 1 here used a memory-probe method which showed that when no position report is required the large number of items that were identified in the Estes and Taylor paradigm is not greater than the number in a posticonic memory. Experiment 2 indicated that when position report is required the number of items identified (with correct position) does not exceed the number which can be reproduced in full report. These results support models in which memory is entailed by identification either as an aspect of the identification process or as a separate stage.", "contents": "Are more items identified than can be reported? Subjects are typically able to report only about four items from a many-item array presented tachistoscopically (full-report span). Current models of visual information processing disagree as to whether the limiting process is best represented as identification or as short-term memory. Estes and Taylor have argued that the number of items identified is up to twice the full-report span and, hence, that memory limits report. Experiment 1 here used a memory-probe method which showed that when no position report is required the large number of items that were identified in the Estes and Taylor paradigm is not greater than the number in a posticonic memory. Experiment 2 indicated that when position report is required the number of items identified (with correct position) does not exceed the number which can be reproduced in full report. These results support models in which memory is entailed by identification either as an aspect of the identification process or as a separate stage."} {"id": "PMID:1271023", "title": "Spatial probability learning by alcoholic Korsakoff patients.", "content": "Performance of 10 alcoholic Korsakoff patients was compared to that of 10 normal and 10 alcoholic control subjects on each of three different schedules of spatial probability learning (50:50, 70:30, and 30:70) using monetary reinforcement and a correction procedure. There was some evidence that the Korsakoff patients were less sensitive than normals to the effects of reward: Although on all three schedules, choice ratios by normal subjects approximated the reinforcement ratios, the choice ratios of Korsakoffs on the second and third schedules remained close to the reinforcement ratio acquired with the first schedule. In addition, the Korsakoffs made an abnormal number of perseverative errors early in training. On most measures, performance by alcoholic controls fell between that of the other two groups.", "contents": "Spatial probability learning by alcoholic Korsakoff patients. Performance of 10 alcoholic Korsakoff patients was compared to that of 10 normal and 10 alcoholic control subjects on each of three different schedules of spatial probability learning (50:50, 70:30, and 30:70) using monetary reinforcement and a correction procedure. There was some evidence that the Korsakoff patients were less sensitive than normals to the effects of reward: Although on all three schedules, choice ratios by normal subjects approximated the reinforcement ratios, the choice ratios of Korsakoffs on the second and third schedules remained close to the reinforcement ratio acquired with the first schedule. In addition, the Korsakoffs made an abnormal number of perseverative errors early in training. On most measures, performance by alcoholic controls fell between that of the other two groups."} {"id": "PMID:1271024", "title": "When preparation fails: disruptive effects of prior information on perceptual recognition.", "content": "There is a conflict in the literature on selective attention. Suppose a subject is briefly presented an item followed by a multiple-alternative recognition test. If the items are pictures, the subject's performance is facilitated by presenting the alternatives beforehand (a before facilitation), but when the items are letters the subjects' performance is disrupted by presenting the alternatives beforehand (a before disruption). Five experiments were conducted to resolve this conflict, and all involved a comparison of tachistoscopic recognition when alternatives were either presented beforehand or not. The first two studies showed that the before disruption with letters was not due to certain task parameters. Experiments 3-5 demonstrated that this effect was due to masking conditions. Experiments 3 and 4 revealed that the disruption occurred only when a mask is used, while the last experiment indicated the disruption effect was sensitive to the type of mask employed. Preseumably, the before disrption arises because a subject erroneously considers the features of a mask along with those of the test item in arriving at a perceptual decision.", "contents": "When preparation fails: disruptive effects of prior information on perceptual recognition. There is a conflict in the literature on selective attention. Suppose a subject is briefly presented an item followed by a multiple-alternative recognition test. If the items are pictures, the subject's performance is facilitated by presenting the alternatives beforehand (a before facilitation), but when the items are letters the subjects' performance is disrupted by presenting the alternatives beforehand (a before disruption). Five experiments were conducted to resolve this conflict, and all involved a comparison of tachistoscopic recognition when alternatives were either presented beforehand or not. The first two studies showed that the before disruption with letters was not due to certain task parameters. Experiments 3-5 demonstrated that this effect was due to masking conditions. Experiments 3 and 4 revealed that the disruption occurred only when a mask is used, while the last experiment indicated the disruption effect was sensitive to the type of mask employed. Preseumably, the before disrption arises because a subject erroneously considers the features of a mask along with those of the test item in arriving at a perceptual decision."} {"id": "PMID:1271025", "title": "U-shaped backward contour masking during stroboscopic motion.", "content": "Two stationary and spatially separated visual stimuli, presented briefly and successively in time, are known to produce stroboscopic motion whose vividness is a U-shaped function of the stimulus onset asynchrony. Contour masking is also known to occur under such stimulus conditions. The findings show that the contour masking is confined to only the first stimulus and that it, like metacontrast, is a backward U-shaped function of the stimulus onset asynchrony. A simple model, based on known psychophysical and neurophysiological properties, is proposed to explain these results.", "contents": "U-shaped backward contour masking during stroboscopic motion. Two stationary and spatially separated visual stimuli, presented briefly and successively in time, are known to produce stroboscopic motion whose vividness is a U-shaped function of the stimulus onset asynchrony. Contour masking is also known to occur under such stimulus conditions. The findings show that the contour masking is confined to only the first stimulus and that it, like metacontrast, is a backward U-shaped function of the stimulus onset asynchrony. A simple model, based on known psychophysical and neurophysiological properties, is proposed to explain these results."} {"id": "PMID:1271026", "title": "Conflicting motion perspective simulating sinultaneous clockwise and counterclockwise rotation in depth.", "content": "Motion projections (pictures) simulating a horizontal array of vertical lines rotating in depth about its central vertical line were observed by 24 college students who rotated a crank handle in the direction of apparent rotation. All displays incorporated contradictory motion perspective: Whereas the perspective transformation in the vertical (y) dimension stimulated one direction of rotation, the transformation in the horizontal (x) dimension simulated the opposite direction. The amount of perspective in each dimension was varied independently of the other by varying the projection ratio used for each dimension. We used the same five ratios for each dimension, combining them factorially to generate the 25 displays. Analysis of variance of the duration of crank turning which agreed with y-axis information yielded main effects of both x and y projection ratios but no interaction, revealing that x- and y-axis motion perspectives mediate kinetic depth effects which are functionally independent.", "contents": "Conflicting motion perspective simulating sinultaneous clockwise and counterclockwise rotation in depth. Motion projections (pictures) simulating a horizontal array of vertical lines rotating in depth about its central vertical line were observed by 24 college students who rotated a crank handle in the direction of apparent rotation. All displays incorporated contradictory motion perspective: Whereas the perspective transformation in the vertical (y) dimension stimulated one direction of rotation, the transformation in the horizontal (x) dimension simulated the opposite direction. The amount of perspective in each dimension was varied independently of the other by varying the projection ratio used for each dimension. We used the same five ratios for each dimension, combining them factorially to generate the 25 displays. Analysis of variance of the duration of crank turning which agreed with y-axis information yielded main effects of both x and y projection ratios but no interaction, revealing that x- and y-axis motion perspectives mediate kinetic depth effects which are functionally independent."} {"id": "PMID:1271027", "title": "Further evidence for two components in visual persistence.", "content": "The phenomenal durations of tachistoscopically presented letter arrays at five levels of redundancy were measured using a subtractive reaction-time technique. Phenomenal duration was inversely related to redundancy only when report of the letters was required. The duration of functional availability of stimulus information for stimuli at the five levels of redundancy was determined in a backward masking paradigm. The measurements of the duration of functional availability and phenomenal presence were convergent, indicating that one process is responsible for both the phenomenal and functional duration of a persisting representation of a visual stimulus. The results are interpreted as providing further evidence for two components in visual persistence: a physical component whose duration is unrelated to stimulus parameters and an informational component whose duration is inversely related to the efficiency of encoding stimulus information.", "contents": "Further evidence for two components in visual persistence. The phenomenal durations of tachistoscopically presented letter arrays at five levels of redundancy were measured using a subtractive reaction-time technique. Phenomenal duration was inversely related to redundancy only when report of the letters was required. The duration of functional availability of stimulus information for stimuli at the five levels of redundancy was determined in a backward masking paradigm. The measurements of the duration of functional availability and phenomenal presence were convergent, indicating that one process is responsible for both the phenomenal and functional duration of a persisting representation of a visual stimulus. The results are interpreted as providing further evidence for two components in visual persistence: a physical component whose duration is unrelated to stimulus parameters and an informational component whose duration is inversely related to the efficiency of encoding stimulus information."} {"id": "PMID:1271028", "title": "Effects of concurrent verbal memory on recognition of stimuli from the left and right visual fields.", "content": "Two experiments examined the effect of concurrently holding 0, 2, 4, or 6 nouns in memory on the recognition of visual stimuli briefly presented to the left or right visual fields. When stimuli to be visually recognized were complex visuospatial forms it was found that a relatively easy memroy load of 2 or 4 nouns improved visual recognition accuracy on right visual field (left-hemisphere) trials relative to the no-memory condition; however, a more difficult memory load of 6 nouns decreased visual recognition accuracy to a level slightly below the no-memory condition. There were no effects of concurrent verbal memroy on visual form recognition on left visual field (right-hemisphere) trials. When the stimuli to be visually recognized were words it was found that a relatively easy memroy load of 2 or 4 nouns improved visual recognition accuracy and a more difficult load of 6 nouns decreased visual recognition accuracy on both left and right visual field trials. The complete pattern of results indicates that several factors including cerebral hemisphere specialization, stimulus codability, selective perceptual orientation, and selective cerebral hemisphere interference interact in systematic ways to produce overall visual laterality effects.", "contents": "Effects of concurrent verbal memory on recognition of stimuli from the left and right visual fields. Two experiments examined the effect of concurrently holding 0, 2, 4, or 6 nouns in memory on the recognition of visual stimuli briefly presented to the left or right visual fields. When stimuli to be visually recognized were complex visuospatial forms it was found that a relatively easy memroy load of 2 or 4 nouns improved visual recognition accuracy on right visual field (left-hemisphere) trials relative to the no-memory condition; however, a more difficult memory load of 6 nouns decreased visual recognition accuracy to a level slightly below the no-memory condition. There were no effects of concurrent verbal memroy on visual form recognition on left visual field (right-hemisphere) trials. When the stimuli to be visually recognized were words it was found that a relatively easy memroy load of 2 or 4 nouns improved visual recognition accuracy and a more difficult load of 6 nouns decreased visual recognition accuracy on both left and right visual field trials. The complete pattern of results indicates that several factors including cerebral hemisphere specialization, stimulus codability, selective perceptual orientation, and selective cerebral hemisphere interference interact in systematic ways to produce overall visual laterality effects."} {"id": "PMID:1271029", "title": "Detection errors on the word the: evidence for reading units larger than letters.", "content": "In four experiments, subjects read 100-word passages and circled instances of the letter t. Subjects missed a disproportionate number of ts in the word the. Evidence was provided against explanations of this effect involving the location and pronunciation of the t in the and against an explanation in terms of the redundancy of the. Rather the high frequency of the appeared to be critical, and it was suggested that high-frequency words are read in terms of units larger than the letter.", "contents": "Detection errors on the word the: evidence for reading units larger than letters. In four experiments, subjects read 100-word passages and circled instances of the letter t. Subjects missed a disproportionate number of ts in the word the. Evidence was provided against explanations of this effect involving the location and pronunciation of the t in the and against an explanation in terms of the redundancy of the. Rather the high frequency of the appeared to be critical, and it was suggested that high-frequency words are read in terms of units larger than the letter."} {"id": "PMID:1271030", "title": "Lexical ambiguity, semantic context, and visual word recognition.", "content": "Some alternative hypotheses about the recognition of ambiguous words are considered. According to the selective-access hypothesis, prior semantic context biases people to access one meaning of an ambiguous word rather than another in lexical memory during recognition. In contrast, the nonselectiveaccess hypothesis states that all meanings of the word are accessed regardless of the context. We tested certain versions of these hypotheses by having students decide whether selected strings of letters were English words. The stimuli included test sequnces of three words in which the second word had two distinct possible meanings, whereas the first and third words were related to these meanings in various ways. When the first and third words were related to the same meaning of the ambiguous second word (e.g., SAVE-BANK-MONEY), the reaction time to recognize the third word decreased. But when the first and third words were related to different meanings of the second word (e.g., RIVER-BANK-MONEY), the reaction time for the third word was not reliably different from a control sequence with unrelated words. These and other data favor the selective-access hypothesis. Selective access to lexical memory is discussed in relation to models of word recognition.", "contents": "Lexical ambiguity, semantic context, and visual word recognition. Some alternative hypotheses about the recognition of ambiguous words are considered. According to the selective-access hypothesis, prior semantic context biases people to access one meaning of an ambiguous word rather than another in lexical memory during recognition. In contrast, the nonselectiveaccess hypothesis states that all meanings of the word are accessed regardless of the context. We tested certain versions of these hypotheses by having students decide whether selected strings of letters were English words. The stimuli included test sequnces of three words in which the second word had two distinct possible meanings, whereas the first and third words were related to these meanings in various ways. When the first and third words were related to the same meaning of the ambiguous second word (e.g., SAVE-BANK-MONEY), the reaction time to recognize the third word decreased. But when the first and third words were related to different meanings of the second word (e.g., RIVER-BANK-MONEY), the reaction time for the third word was not reliably different from a control sequence with unrelated words. These and other data favor the selective-access hypothesis. Selective access to lexical memory is discussed in relation to models of word recognition."} {"id": "PMID:1271031", "title": "Processing two dimensions of nonspeech stimuli: the auditory-phonetic distinction reconsidered.", "content": "Nonspeech stimuli were varied along two dimensions--intensity and rise time. In a series of speeded classification tasks, subjected were asked to identify the stimuli in terms of one of these dimensions. Identification time for the dimension of rise time increased when there was irrelevant variation in intensity; however, identification of intensity was unaffected by irrelevant variation in rise time. When the two dimensions varied redundantly, identification time decreased. This pattern of results is virtually identical to that obtained previously for stimuli that vary along a linguistic and a nonlinguistic dimension. The present data, taken together with those from other studies using the same stimuli, suggest that the mechanisms underlying the auditory-phonetic distinction should be reconsidered. The results are also discussed in terms of general models of multidimensional information processing.", "contents": "Processing two dimensions of nonspeech stimuli: the auditory-phonetic distinction reconsidered. Nonspeech stimuli were varied along two dimensions--intensity and rise time. In a series of speeded classification tasks, subjected were asked to identify the stimuli in terms of one of these dimensions. Identification time for the dimension of rise time increased when there was irrelevant variation in intensity; however, identification of intensity was unaffected by irrelevant variation in rise time. When the two dimensions varied redundantly, identification time decreased. This pattern of results is virtually identical to that obtained previously for stimuli that vary along a linguistic and a nonlinguistic dimension. The present data, taken together with those from other studies using the same stimuli, suggest that the mechanisms underlying the auditory-phonetic distinction should be reconsidered. The results are also discussed in terms of general models of multidimensional information processing."} {"id": "PMID:1271032", "title": "Processing interaction between two dimensions of nonphonetic auditory signals.", "content": "In 1974 Wood proposed a hybrid serial-parallel model to account for the within-stimulus interactions between the acoustic cue of \"pitch\" and the phonetic cure of \"place.\" Three of the five experiments in this paper replicate the Wood findings with analogous, clearly nonphonetic stimuli and thus refute Wood's implicit assumption of the involvement of any uniquely phonetic processes as factors in his results. The experiments in this paper demonstrate that the patterns of interaction found by Wood are independent of the experience of the subjects, the order of cue presentation, and whether the cues are presented simultaneously or sequentially. We conclude that the given patterns of interaction are general characteristics of the auditory system. These characteristics probably are not related to backward or forward \"recognition\" masking but may be a function of several other general factors.", "contents": "Processing interaction between two dimensions of nonphonetic auditory signals. In 1974 Wood proposed a hybrid serial-parallel model to account for the within-stimulus interactions between the acoustic cue of \"pitch\" and the phonetic cure of \"place.\" Three of the five experiments in this paper replicate the Wood findings with analogous, clearly nonphonetic stimuli and thus refute Wood's implicit assumption of the involvement of any uniquely phonetic processes as factors in his results. The experiments in this paper demonstrate that the patterns of interaction found by Wood are independent of the experience of the subjects, the order of cue presentation, and whether the cues are presented simultaneously or sequentially. We conclude that the given patterns of interaction are general characteristics of the auditory system. These characteristics probably are not related to backward or forward \"recognition\" masking but may be a function of several other general factors."} {"id": "PMID:1271033", "title": "Reaction time to temporally-displaced phoneme targets in continuous speech.", "content": "In seven experiments, reaction time (RT) was recorded to phoneme targets in sentences. By means of tape splicing or other experimental interventions preceding the target, speech information was or was not discarded, and targets were either temporally displaced \"early\" or \"late\" or remained on time.\" RT to displaced targets was slower than to on-time targets, except when the tape-splicing manipulation in effect presented coarticulatory target information in advance, in which case RT was faster than RT to on-time targets. The latter manipulation also produced faster RT than RT to the same targets in the original sentence, that is, that containing no experimental intervention at all. In three of the experiments, half the targets were contained in stressed syllables, half in unstressed syllables. Stressed and unstressed targets were affected differently, depending upon practice and other factors. Results were interpreted in terms of listener expectancies based on timing redundancy in continuous speech. They indicate an interaction between the effects of segmental and suprasegmental cues during ongoing perception.", "contents": "Reaction time to temporally-displaced phoneme targets in continuous speech. In seven experiments, reaction time (RT) was recorded to phoneme targets in sentences. By means of tape splicing or other experimental interventions preceding the target, speech information was or was not discarded, and targets were either temporally displaced \"early\" or \"late\" or remained on time.\" RT to displaced targets was slower than to on-time targets, except when the tape-splicing manipulation in effect presented coarticulatory target information in advance, in which case RT was faster than RT to on-time targets. The latter manipulation also produced faster RT than RT to the same targets in the original sentence, that is, that containing no experimental intervention at all. In three of the experiments, half the targets were contained in stressed syllables, half in unstressed syllables. Stressed and unstressed targets were affected differently, depending upon practice and other factors. Results were interpreted in terms of listener expectancies based on timing redundancy in continuous speech. They indicate an interaction between the effects of segmental and suprasegmental cues during ongoing perception."} {"id": "PMID:1271034", "title": "An experimental test of two mathematical models applied to the size-weight illusion.", "content": "Two quantitative models, which make different quantitative predictions for the amount of the size-weight illusion, were tested according to the psychophysical methods employed by the respective authors (magnitude estimation versus category ratings). Both models with their corresponding method were supported. This causes uncertainty over Anderson's chaim that the validity of both a model and the applied scale used is sufficiently test by the socalled joint testing procedure.", "contents": "An experimental test of two mathematical models applied to the size-weight illusion. Two quantitative models, which make different quantitative predictions for the amount of the size-weight illusion, were tested according to the psychophysical methods employed by the respective authors (magnitude estimation versus category ratings). Both models with their corresponding method were supported. This causes uncertainty over Anderson's chaim that the validity of both a model and the applied scale used is sufficiently test by the socalled joint testing procedure."} {"id": "PMID:1271035", "title": "Extra cytoproct mutant in Paramecium tetraurelia: morphogenetical analysis of proters and opisthes.", "content": "To account for the differences between proters and opisthes with regard to extra cytoproct morphogenesis in Paramecium tetraurelia, two hypotheses have been proposed and tested. (i) The differences may be a result of different actions of proter-macronucleus and opisthe-macronucleus. This hypothesis has been tested by cytoplasmically connecting the proter with the opisthe in the form of chains, some of which have only one macronucleus per chain. However, the connected proters and opisthes remain different in extra cytoproct morphogenesis, thus arguing against the hypothesis. (ii) The differences may be a result of differences between the proter and the opisthe with regard to the development of their posterior-ventral cortex: proters have a newly-developed posterior-ventral cortex whereas opisthes receive the posterior-ventral cortex from the pre-fission mother animal. This hypothesis has been tested by surgically producing an opisthe with a newly-regenerated posterior cortex. Such opisthes, however, remain different from proters in extra cytoproct morphogenesis. Thus no direct support for the second hypothesis is obtained. Also, proter-opisthe difference in morphogenesis may be understood in terms of Wolpert's positional information hypothesis, by assuming that the anterior and posterior ends of a dividing animal serve as reference points for establishing a gradient and that positional information before separation of the two daughter animals leads to differences in extra cytoproct morphogenesis between them after separation.", "contents": "Extra cytoproct mutant in Paramecium tetraurelia: morphogenetical analysis of proters and opisthes. To account for the differences between proters and opisthes with regard to extra cytoproct morphogenesis in Paramecium tetraurelia, two hypotheses have been proposed and tested. (i) The differences may be a result of different actions of proter-macronucleus and opisthe-macronucleus. This hypothesis has been tested by cytoplasmically connecting the proter with the opisthe in the form of chains, some of which have only one macronucleus per chain. However, the connected proters and opisthes remain different in extra cytoproct morphogenesis, thus arguing against the hypothesis. (ii) The differences may be a result of differences between the proter and the opisthe with regard to the development of their posterior-ventral cortex: proters have a newly-developed posterior-ventral cortex whereas opisthes receive the posterior-ventral cortex from the pre-fission mother animal. This hypothesis has been tested by surgically producing an opisthe with a newly-regenerated posterior cortex. Such opisthes, however, remain different from proters in extra cytoproct morphogenesis. Thus no direct support for the second hypothesis is obtained. Also, proter-opisthe difference in morphogenesis may be understood in terms of Wolpert's positional information hypothesis, by assuming that the anterior and posterior ends of a dividing animal serve as reference points for establishing a gradient and that positional information before separation of the two daughter animals leads to differences in extra cytoproct morphogenesis between them after separation."} {"id": "PMID:1271036", "title": "Maturation and sperm penetration of canine ovarian oocytes in vitro.", "content": "Canine ovarian oocytes were cultured in a medium consisting of TC medium 199, fetal calf serum and antibiotics. Ninety-nine percent of the apparently healthy oocytes were in the germinal vesicle (dictyate) stage when recovered from the ovaries; 25% of them reached metaphase I or II by 72 hours of culture. Washed ejaculated spermatozoa were added to BWW medium containing oocytes which had either been removed directly from the follicles or which had been cultured for 24--72 hours. The earliest acrosome reaction and zona penetration by spermatozoa were seen at seven hours after insemination. Seventy-four percent of the oocytes examined between 11 and 24 hours after insemination showed evidence of zona penetration by spermatozoa. Neither the condition of the oocyte vitellus nor the stage of nuclear maturation influenced the incidence of zona penetration. Decondensing sperm nuclei were found in the vitellus of 27% of the oocytes which had not been cultured and in the vitellus of 20% of those which had been cultured for 24--72 hours and were in various stages of maturation. These results indicate that (1) canine ovarian oocytes can be matured in vitro, (2) the spermatozoa require capacitation which takes approximately seven hours in vitro and (3) maturation of the oocytes is not required for sperm passage through the zona pellucida or entry into the vitellus nor for sperm nuclear decondensation.", "contents": "Maturation and sperm penetration of canine ovarian oocytes in vitro. Canine ovarian oocytes were cultured in a medium consisting of TC medium 199, fetal calf serum and antibiotics. Ninety-nine percent of the apparently healthy oocytes were in the germinal vesicle (dictyate) stage when recovered from the ovaries; 25% of them reached metaphase I or II by 72 hours of culture. Washed ejaculated spermatozoa were added to BWW medium containing oocytes which had either been removed directly from the follicles or which had been cultured for 24--72 hours. The earliest acrosome reaction and zona penetration by spermatozoa were seen at seven hours after insemination. Seventy-four percent of the oocytes examined between 11 and 24 hours after insemination showed evidence of zona penetration by spermatozoa. Neither the condition of the oocyte vitellus nor the stage of nuclear maturation influenced the incidence of zona penetration. Decondensing sperm nuclei were found in the vitellus of 27% of the oocytes which had not been cultured and in the vitellus of 20% of those which had been cultured for 24--72 hours and were in various stages of maturation. These results indicate that (1) canine ovarian oocytes can be matured in vitro, (2) the spermatozoa require capacitation which takes approximately seven hours in vitro and (3) maturation of the oocytes is not required for sperm passage through the zona pellucida or entry into the vitellus nor for sperm nuclear decondensation."} {"id": "PMID:1271037", "title": "Changes in the tail of Ambystoma maculatum at different stages of metamorphosis: observations on tissue remodeling and its relationship to hydrolytic enzymes.", "content": "A system for staging A. maculatum during growth and metamorphosis was devised, based on several parameters of body size; body length, tail length and tail width. Animals at various stages of metamorphosis were employed to study the relationship between specific biochemical and histological changes that occur in the tail of this urodele during metamorphosis. The specific and total activity of two hydrolytic enzymes, acid phosphatase and beta-N-acetyl-glucosaminidase, were measured in tail tissues at progressive stages of development. The activities of these enzymes increased in both the fins and muscular portion of the tail during metamorphosis. These activities can be correlated with resorption of the tail fins and the remodeling of tissues in the muscular portion of the tail.", "contents": "Changes in the tail of Ambystoma maculatum at different stages of metamorphosis: observations on tissue remodeling and its relationship to hydrolytic enzymes. A system for staging A. maculatum during growth and metamorphosis was devised, based on several parameters of body size; body length, tail length and tail width. Animals at various stages of metamorphosis were employed to study the relationship between specific biochemical and histological changes that occur in the tail of this urodele during metamorphosis. The specific and total activity of two hydrolytic enzymes, acid phosphatase and beta-N-acetyl-glucosaminidase, were measured in tail tissues at progressive stages of development. The activities of these enzymes increased in both the fins and muscular portion of the tail during metamorphosis. These activities can be correlated with resorption of the tail fins and the remodeling of tissues in the muscular portion of the tail."} {"id": "PMID:1271038", "title": "Regenerative abnormalities in Notophthalmus viridescens induced by repeated amputations.", "content": "The fidelity of the regenerative response in the adult newt, Notophthalmus viridescens, was examined following repeated amputations at the level of the distal one-third of humerus. Three to four months following amputation, all regenerates were scored for gross morphology, reamputated, and stained with methylene blue for skeletal elements. The occurrence of abnormal regeneration with respect both to gross morphology and to skeletal structure was found to increase directly with the number of times the limb stumps were required to initiate dedifferentiation and repair. The initial amputation-regeneration process produced structurally normal replacement limbs in 91% of the cases examined. Reamputations of 4-digit regenerates (3--4 months after the previous transection) resulted in structurally abnormal regenerates in 28% of the cases following two amputations; 50% of the cases following three amputations; 65% of the cases following four amputations; and 81% of the cases following five amputations. The relationships between repeated dedifferentiation, proliferation, and redifferentiation and normal limb development are discussed.", "contents": "Regenerative abnormalities in Notophthalmus viridescens induced by repeated amputations. The fidelity of the regenerative response in the adult newt, Notophthalmus viridescens, was examined following repeated amputations at the level of the distal one-third of humerus. Three to four months following amputation, all regenerates were scored for gross morphology, reamputated, and stained with methylene blue for skeletal elements. The occurrence of abnormal regeneration with respect both to gross morphology and to skeletal structure was found to increase directly with the number of times the limb stumps were required to initiate dedifferentiation and repair. The initial amputation-regeneration process produced structurally normal replacement limbs in 91% of the cases examined. Reamputations of 4-digit regenerates (3--4 months after the previous transection) resulted in structurally abnormal regenerates in 28% of the cases following two amputations; 50% of the cases following three amputations; 65% of the cases following four amputations; and 81% of the cases following five amputations. The relationships between repeated dedifferentiation, proliferation, and redifferentiation and normal limb development are discussed."} {"id": "PMID:1271039", "title": "Putative synaptic mechanisms of inhibition in Limulus lateral eye.", "content": "Serotonin (5-HT) perfusion of a thin section of Limulus lateral eye hyperpolarizes retinular and eccentric cell membrane potential, and blocks spike action potentials fired by the eccenteric cell. The indoleamine does not directly affect retinular cell receptor potential or eccenteric cell generator potential in response to light stimuli. LSD perfusion blocks both this inhibitory action of 5-HT and light-evoked, synaptically mediated, lateral inhibition. Iontophoretic application of 5-HT to the synaptic neuropil produces shorter latency and duration and larger amplitude of inhibition than does the perfusion technique. This inhibition is dose dependent; the accompanying inhibitory postsynaptic potential (IPSP) appears to have an equilibrium potential more hyperpolarized than normal resting potential levels of ca. -50 mV. IPSP amplitude is sensitive to extracellular potassium ion concentration: it increases with decreased [K+]0 and decreases with increased [K+]0. LSD blocks the inhibition produced by iontophoretic application of 5-HT. Interaction between light-evoked, natural synaptic transmitter-mediated IPSP's and 5-HT IPSP's suggests a common postsynaptic receptor or transmitter-receptor-permeability change mechanism.", "contents": "Putative synaptic mechanisms of inhibition in Limulus lateral eye. Serotonin (5-HT) perfusion of a thin section of Limulus lateral eye hyperpolarizes retinular and eccentric cell membrane potential, and blocks spike action potentials fired by the eccenteric cell. The indoleamine does not directly affect retinular cell receptor potential or eccenteric cell generator potential in response to light stimuli. LSD perfusion blocks both this inhibitory action of 5-HT and light-evoked, synaptically mediated, lateral inhibition. Iontophoretic application of 5-HT to the synaptic neuropil produces shorter latency and duration and larger amplitude of inhibition than does the perfusion technique. This inhibition is dose dependent; the accompanying inhibitory postsynaptic potential (IPSP) appears to have an equilibrium potential more hyperpolarized than normal resting potential levels of ca. -50 mV. IPSP amplitude is sensitive to extracellular potassium ion concentration: it increases with decreased [K+]0 and decreases with increased [K+]0. LSD blocks the inhibition produced by iontophoretic application of 5-HT. Interaction between light-evoked, natural synaptic transmitter-mediated IPSP's and 5-HT IPSP's suggests a common postsynaptic receptor or transmitter-receptor-permeability change mechanism."} {"id": "PMID:1271040", "title": "Nonuniform distribution of sodium in the rat hepatocyte.", "content": "The volume of the nucleus, endoplasmic reticulum (including Golgi complex), mitochondria, and cytoplasmic ground substance was measured in rat hepatocytes by stereological methods. The Na content was also measured by flame photometry. Variations in Na content correlated significantly with variations in volume of nucleus and endoplasmic reticulum. From the correlation parameters, Na concentrations were estimated as follows: nucleus, 108 mM; endoplasmic reticulum (ER) (including Golgie complex) 27 mM; cytoplasm (including and remaining organelles) 16 mM.", "contents": "Nonuniform distribution of sodium in the rat hepatocyte. The volume of the nucleus, endoplasmic reticulum (including Golgi complex), mitochondria, and cytoplasmic ground substance was measured in rat hepatocytes by stereological methods. The Na content was also measured by flame photometry. Variations in Na content correlated significantly with variations in volume of nucleus and endoplasmic reticulum. From the correlation parameters, Na concentrations were estimated as follows: nucleus, 108 mM; endoplasmic reticulum (ER) (including Golgie complex) 27 mM; cytoplasm (including and remaining organelles) 16 mM."} {"id": "PMID:1271041", "title": "Comparison of the side-dependent effects of Na and K on orthophosphate-, UTP-, and ATP-promoted ouabain binding to reconstituted human red blood cell ghosts.", "content": "This paper is concerned with analyzing the sidedness of action of various determinants which alter the rate of ouabain binding to human red blood cell ghosts. Thus, ouabain binding promoted by orthophosphate (Pi) and its inhibition by Na are shown to be due to inside Pi and inside Na. External K inhibits Pi-promoted ouabain binding and Nao acts to decrease the effectiveness of Ko. Similarly, inside uridine triphosphate (UTPi) stimulates the rate of ouabain binding which can be antagonized by either Nai or Ko acting alone. The actions of Nai and Ko are different when ouabain binding is promoted by Pi and UTPi compared to inside adenosine triphosphate (ATPi). With ATPi, the ouabain binding rate is only affected when Nai and Ko are both present. Possible differences in the mechanism of action of K and Na on Pi-and UTP-promoted binding are discussed in the light of their sidedness of action.", "contents": "Comparison of the side-dependent effects of Na and K on orthophosphate-, UTP-, and ATP-promoted ouabain binding to reconstituted human red blood cell ghosts. This paper is concerned with analyzing the sidedness of action of various determinants which alter the rate of ouabain binding to human red blood cell ghosts. Thus, ouabain binding promoted by orthophosphate (Pi) and its inhibition by Na are shown to be due to inside Pi and inside Na. External K inhibits Pi-promoted ouabain binding and Nao acts to decrease the effectiveness of Ko. Similarly, inside uridine triphosphate (UTPi) stimulates the rate of ouabain binding which can be antagonized by either Nai or Ko acting alone. The actions of Nai and Ko are different when ouabain binding is promoted by Pi and UTPi compared to inside adenosine triphosphate (ATPi). With ATPi, the ouabain binding rate is only affected when Nai and Ko are both present. Possible differences in the mechanism of action of K and Na on Pi-and UTP-promoted binding are discussed in the light of their sidedness of action."} {"id": "PMID:1271042", "title": "Effects of Mg and Ca on the side dependencies of Na and K on ouabain binding to red blood cell ghosts and the control of Na transport by internal Mg.", "content": "The effect of alteration in the concentration of internal Mg on the rate of ouabain binding to reconstituted human red blood cell ghosts has been evaluated as well as the effect of Mgi on Na:Na compared to Na:K exchange. It was found that the dependence of the rate of ATP-promoted ouabain binding on the combined presence of Nai and Ko which occurs at high [Mg]i is lost when the concentration of Mgi is lowered. The sensitivity of the external surface for Ko is also changed since Ko can now inhibit the ouabain binding rate in the absence of Nai; on the other hand Nao at low [Mg]i can stimulate ouabain binding indicating that the relative affinity of the outside surface for Nao has either increased or that for Ko has decreased or both. Thus the effects of changes in [Mg]i result in a change in the side-dependent actions of Na and K and emphasize the possible difficulties of interpreting results obtained on systems lacking sidedness. Mgi was found to be required for Pi-promoted ouabain binding and that the inhibitory action of Nai increased as [Mg]i was increased. In addition, Ca was found to be most effective in inhibiting the rate of ATP-promoted ouabain binding when Na and K were present together than when either was present alone. Na:K exchange was found to be more sensitive to the concentration of Mgi than Na:Na exchange; at low [Mg]i Na:K exchange could be stimulated without changing the extent of Na:Na exchange. These results are consistent with the idea that conformational states of the pump complex are directly influenced by [Mg]i.", "contents": "Effects of Mg and Ca on the side dependencies of Na and K on ouabain binding to red blood cell ghosts and the control of Na transport by internal Mg. The effect of alteration in the concentration of internal Mg on the rate of ouabain binding to reconstituted human red blood cell ghosts has been evaluated as well as the effect of Mgi on Na:Na compared to Na:K exchange. It was found that the dependence of the rate of ATP-promoted ouabain binding on the combined presence of Nai and Ko which occurs at high [Mg]i is lost when the concentration of Mgi is lowered. The sensitivity of the external surface for Ko is also changed since Ko can now inhibit the ouabain binding rate in the absence of Nai; on the other hand Nao at low [Mg]i can stimulate ouabain binding indicating that the relative affinity of the outside surface for Nao has either increased or that for Ko has decreased or both. Thus the effects of changes in [Mg]i result in a change in the side-dependent actions of Na and K and emphasize the possible difficulties of interpreting results obtained on systems lacking sidedness. Mgi was found to be required for Pi-promoted ouabain binding and that the inhibitory action of Nai increased as [Mg]i was increased. In addition, Ca was found to be most effective in inhibiting the rate of ATP-promoted ouabain binding when Na and K were present together than when either was present alone. Na:K exchange was found to be more sensitive to the concentration of Mgi than Na:Na exchange; at low [Mg]i Na:K exchange could be stimulated without changing the extent of Na:Na exchange. These results are consistent with the idea that conformational states of the pump complex are directly influenced by [Mg]i."} {"id": "PMID:1271043", "title": "Sodium permeability of dog red blood cell membranes. I. Identification of regulatory sites.", "content": "Divalent cations and group-specific chemical modifiers were used to modify sodium efflux in order to probe the molecular structure of sodium channels in dog red blood cells. Hg++, Ni++, Co++, and PCMBS (parachloromercuribenzene sulfonic acid), a sulfhydryl reactive reagent, induce large increases in Na+ permeability and their effects can be described by a curve which assumes 2:1 binding with the sodium channel. The sequence of affinities, as measured by the dissociation constants, reflects the reactivity of these divalent cations with sulfhydryl groups. In addition, the effects of Hg++ and PCMBS can be reversed by the addition of dithiothreitol, an SH-containing compound, to the medium. Much smaller increases in Na+ permeability are produced by Zn++ and the amino-specific reagents, TNBS (2,4,6-trinitrobenzene sulfonic acid) and SITS (4-acetamido-4'-isothiocyano-stilbene-2-2'-disulfonic acid). The Zn++ effect can be described by a curve which assumes bimolecular binding with the channel, and its effect on Na+ permeability can be reversed by the addition of glycine to the medium. The effects of Ni++ and SITS can be completely reversed by washing the cells in 0.16 M NaCl while TNBS binding is partially irreversible. Measurements of mean cell volumes (MCV) indicate that the modifier-induced increases in Na+ permeability are not caused by shrinkage of the cells. It is concluded that the movement of sodium ions through ionic channels in dog red blood cells can be enhanced by modification of amino and sulfhydryl groups. Zn++, TNBS, and SITS increase Na+ permeability by modifying amino groups in the channel while Hg++, Ni++, Co++, and PCMBS act on sulfhydryl groups.", "contents": "Sodium permeability of dog red blood cell membranes. I. Identification of regulatory sites. Divalent cations and group-specific chemical modifiers were used to modify sodium efflux in order to probe the molecular structure of sodium channels in dog red blood cells. Hg++, Ni++, Co++, and PCMBS (parachloromercuribenzene sulfonic acid), a sulfhydryl reactive reagent, induce large increases in Na+ permeability and their effects can be described by a curve which assumes 2:1 binding with the sodium channel. The sequence of affinities, as measured by the dissociation constants, reflects the reactivity of these divalent cations with sulfhydryl groups. In addition, the effects of Hg++ and PCMBS can be reversed by the addition of dithiothreitol, an SH-containing compound, to the medium. Much smaller increases in Na+ permeability are produced by Zn++ and the amino-specific reagents, TNBS (2,4,6-trinitrobenzene sulfonic acid) and SITS (4-acetamido-4'-isothiocyano-stilbene-2-2'-disulfonic acid). The Zn++ effect can be described by a curve which assumes bimolecular binding with the channel, and its effect on Na+ permeability can be reversed by the addition of glycine to the medium. The effects of Ni++ and SITS can be completely reversed by washing the cells in 0.16 M NaCl while TNBS binding is partially irreversible. Measurements of mean cell volumes (MCV) indicate that the modifier-induced increases in Na+ permeability are not caused by shrinkage of the cells. It is concluded that the movement of sodium ions through ionic channels in dog red blood cells can be enhanced by modification of amino and sulfhydryl groups. Zn++, TNBS, and SITS increase Na+ permeability by modifying amino groups in the channel while Hg++, Ni++, Co++, and PCMBS act on sulfhydryl groups."} {"id": "PMID:1271044", "title": "Ion transport studies and determination of the cell wall elastic modulus in the marine alga Halicystis parvula.", "content": "Using cultured cells of the marine alga, Halicystis parvula, we measured the concentrations of 11 inorganic ions in the vacuolar sap and the electrical potential difference (PD) between the vacuole and the external solution. In normal cells under steady-state conditions a comparison of the electrochemical equilibrium (Nernst) potential for each ion with the PD of -82 mV (inside negative) indicates that Na+ and K+ are actively transported out of the vacuole whereas all anions are pumped into the cell. Although the [K+] in the vacuole is only 9 mM, the cytoplasmic [K+] is about 420 mM, which suggests that the outwardly directed pump is at the tonoplast. Using large Halicystis cells we perfused the vacuole with an artificial seawater and conducted a short-circuit analysis of ion transport. The short-circuit current (SCC) of 299 peq - cm-2-s-1 is not significantly different from the net influx of Cl-. There is a small, but statistically significant net efflux of K+ (less than 1 pmol-cm-2.-1), while the influx and efflux of Na+ are not significantly different. Therefore, the SCC is a good measure of the activity of the Cl- pump. Finally, we measured the volumetric elastic modulus (epsilon) of the cell wall by measuring the change in cell volume when the internal hydrostatic pressure was altered. The value of epsilon at applied pressures between 0 and 0.4 atm is about 0.6 atm, which is at least 100-fold lower than the values of epsilon for all other algae which have been studied.", "contents": "Ion transport studies and determination of the cell wall elastic modulus in the marine alga Halicystis parvula. Using cultured cells of the marine alga, Halicystis parvula, we measured the concentrations of 11 inorganic ions in the vacuolar sap and the electrical potential difference (PD) between the vacuole and the external solution. In normal cells under steady-state conditions a comparison of the electrochemical equilibrium (Nernst) potential for each ion with the PD of -82 mV (inside negative) indicates that Na+ and K+ are actively transported out of the vacuole whereas all anions are pumped into the cell. Although the [K+] in the vacuole is only 9 mM, the cytoplasmic [K+] is about 420 mM, which suggests that the outwardly directed pump is at the tonoplast. Using large Halicystis cells we perfused the vacuole with an artificial seawater and conducted a short-circuit analysis of ion transport. The short-circuit current (SCC) of 299 peq - cm-2-s-1 is not significantly different from the net influx of Cl-. There is a small, but statistically significant net efflux of K+ (less than 1 pmol-cm-2.-1), while the influx and efflux of Na+ are not significantly different. Therefore, the SCC is a good measure of the activity of the Cl- pump. Finally, we measured the volumetric elastic modulus (epsilon) of the cell wall by measuring the change in cell volume when the internal hydrostatic pressure was altered. The value of epsilon at applied pressures between 0 and 0.4 atm is about 0.6 atm, which is at least 100-fold lower than the values of epsilon for all other algae which have been studied."} {"id": "PMID:1271045", "title": "Control of action potential duration by calcium ions in cardiac Purkinje fibers.", "content": "It is well known that cardiac action potentials are shortened by increasing the external calcium concentration (Cao). The shortening is puzzling since Ca ions are thought to carry inward current during the plateau. We therefore studied the effects of Cao on action potentials and membrane currents in short Purkinje fiber preparations. Two factors favor the earlier repolarization. First, calcium-rich solutions generally raise the plateau voltage; in turn, the higher plateau level accelerates time- and voltage-dependent current changes which trigger repolarization. Increases in plateau height imposed by depolarizing current consistently produced shortening of the action potential. The second factor in the action of Ca ions involves iK1, the background K current (inward rectifier). Raising Cao enhances iK1 and thus favors faster repolarization. The Ca-sensitive current change was identified as an increase in iK1 by virtue of its dependence on membrane potential and Ko. A possible third factor was considered and ruled out: unlike epinephrine, calcium-rich solutions do not enhance slow outward plateau current, ikappa. These results are surprising in showing that calcium ions and epinephrine act quite differently on repolarizing currents, even though they share similar effects on the height and duration of the action potential.", "contents": "Control of action potential duration by calcium ions in cardiac Purkinje fibers. It is well known that cardiac action potentials are shortened by increasing the external calcium concentration (Cao). The shortening is puzzling since Ca ions are thought to carry inward current during the plateau. We therefore studied the effects of Cao on action potentials and membrane currents in short Purkinje fiber preparations. Two factors favor the earlier repolarization. First, calcium-rich solutions generally raise the plateau voltage; in turn, the higher plateau level accelerates time- and voltage-dependent current changes which trigger repolarization. Increases in plateau height imposed by depolarizing current consistently produced shortening of the action potential. The second factor in the action of Ca ions involves iK1, the background K current (inward rectifier). Raising Cao enhances iK1 and thus favors faster repolarization. The Ca-sensitive current change was identified as an increase in iK1 by virtue of its dependence on membrane potential and Ko. A possible third factor was considered and ruled out: unlike epinephrine, calcium-rich solutions do not enhance slow outward plateau current, ikappa. These results are surprising in showing that calcium ions and epinephrine act quite differently on repolarizing currents, even though they share similar effects on the height and duration of the action potential."} {"id": "PMID:1271046", "title": "Adult \"failure-to-thrive\" syndrome.", "content": "The analogy between the \"failure-to-thrive\" syndrome of childhood and a symptom complex seen in adult neurology is described. Adults presenting with a variety of central nervous system diseases occasionally seem to follow an unusual stereotyped course resulting in intractable weight loss, wide variations in temperature, and a tendency to intractable decubitus ulcerations in a setting of decreased levels of consciousness. Sudden death occurs unexpectedly. This syndrome can be observed following cerebral thrombosis, traumatic encephalopathy, degenerative central nervous system disorders, and encephalitis. The pathophysiology is thought to result from the random aggregate of lesions rather than a verifiable discrete hypothalamic deficit.", "contents": "Adult \"failure-to-thrive\" syndrome. The analogy between the \"failure-to-thrive\" syndrome of childhood and a symptom complex seen in adult neurology is described. Adults presenting with a variety of central nervous system diseases occasionally seem to follow an unusual stereotyped course resulting in intractable weight loss, wide variations in temperature, and a tendency to intractable decubitus ulcerations in a setting of decreased levels of consciousness. Sudden death occurs unexpectedly. This syndrome can be observed following cerebral thrombosis, traumatic encephalopathy, degenerative central nervous system disorders, and encephalitis. The pathophysiology is thought to result from the random aggregate of lesions rather than a verifiable discrete hypothalamic deficit."} {"id": "PMID:1271047", "title": "The development and validation of a measure of the psychiatrist's authoritative domain.", "content": "In order to examine issues relevant to the authority which patients bestow upon psychiatrists the present authors constructed the Psychiatrist's Sphere of Influence Scale (PSIS). The PSIS is a 68-item Likert-type questionnaire which asks patients to specify the skills which they believe belong to the psychiatrist's authoritative domain. Patients being treated in day hospital (N=82), inpatient (N=113), and outpatient (N=121) settings were individually administered the PSIS along with various discriminant and construct validity measures. The findings indicated that the PSIS is an internally consistent, factorially complex, relatively stable measure of the roles which are ascribed to psychiatrists. Neither the social desirability nor the agreement response set represents important contaminants of the PSIS. Moreover, individual differences on the PSIS appear to be predictable, within broad limits, from patients' positions in the social structure, their preferred styles of help seeking in hospital and therapy settings, and their generalized orientations toward power and authority. A tendency to blur the boundaries between \"psychiatric\" and \"nonpsychiatric\" roles appears to be concentrated among patients who are middle-aged or older, minimally educated, of lower socioeconomic status, inclined toward an authoritarian conception of the good patient and the good hospital, and who endorse traditional family role relationships. The implications of these findings for the manner in which psychiatrists exercise their authority were discussed.", "contents": "The development and validation of a measure of the psychiatrist's authoritative domain. In order to examine issues relevant to the authority which patients bestow upon psychiatrists the present authors constructed the Psychiatrist's Sphere of Influence Scale (PSIS). The PSIS is a 68-item Likert-type questionnaire which asks patients to specify the skills which they believe belong to the psychiatrist's authoritative domain. Patients being treated in day hospital (N=82), inpatient (N=113), and outpatient (N=121) settings were individually administered the PSIS along with various discriminant and construct validity measures. The findings indicated that the PSIS is an internally consistent, factorially complex, relatively stable measure of the roles which are ascribed to psychiatrists. Neither the social desirability nor the agreement response set represents important contaminants of the PSIS. Moreover, individual differences on the PSIS appear to be predictable, within broad limits, from patients' positions in the social structure, their preferred styles of help seeking in hospital and therapy settings, and their generalized orientations toward power and authority. A tendency to blur the boundaries between \"psychiatric\" and \"nonpsychiatric\" roles appears to be concentrated among patients who are middle-aged or older, minimally educated, of lower socioeconomic status, inclined toward an authoritarian conception of the good patient and the good hospital, and who endorse traditional family role relationships. The implications of these findings for the manner in which psychiatrists exercise their authority were discussed."} {"id": "PMID:1271048", "title": "Forensic psychiatry: diagnosis and criminal responsibility.", "content": "An examination of the primary and secondary diagnoses of 1195 defendants admitted to an urban forensic service was carried out. This indicated that personality disorders dominated the referral patterns from the court. Of those conditions which could produce thought disorders, schizophrenia dominated. An analysis of the prevalence of schizophrenia among defendants charged with homicide in St. Louis revealed a rate of schizophrenia similar to that found in the general population. Organic brain syndromes resulted in a large proportion of assaultive behavior, and these cases also involved a large number of secondary diagnoses. Alcohol and drug abuse were the most common secondary diagnoses. In general, no correlation between psychiatric diagnosis and types of criminal activity was found.", "contents": "Forensic psychiatry: diagnosis and criminal responsibility. An examination of the primary and secondary diagnoses of 1195 defendants admitted to an urban forensic service was carried out. This indicated that personality disorders dominated the referral patterns from the court. Of those conditions which could produce thought disorders, schizophrenia dominated. An analysis of the prevalence of schizophrenia among defendants charged with homicide in St. Louis revealed a rate of schizophrenia similar to that found in the general population. Organic brain syndromes resulted in a large proportion of assaultive behavior, and these cases also involved a large number of secondary diagnoses. Alcohol and drug abuse were the most common secondary diagnoses. In general, no correlation between psychiatric diagnosis and types of criminal activity was found."} {"id": "PMID:1271049", "title": "Therapeutic implications of tricyclic antidepressant plasma levels.", "content": "Methodological advances in drug assay techniques and their increasing availability have made the measurement of tricyclic antidepressant plasma levels more frequent and even fashionable. Plasma levels of tricyclics have been correlated with diagnosis, prognosis, clinical response, and side effects. But even in the area most extensively examined, the correlation between plasma level and clinical response, the results have been conflicting. Different studies have suggested that there is no relationship between plasma level and clinical response, as well as positive and negative correlations, and even a curvilinear relationship. On the basis of available evidence, it is impossible to define a therapeutic range of plasma levels that will be applicable to depressed patients as a group. For the moment, the problem of finding a suitable therapeutic dose for the individual patient remains of paramount importance. Studies to date suggest the need to take into consideration genetic factors, previous and present use of other drugs, the possibility that therapeutic failure might be a result of too high as well as too low a dose, as well as the possible relationship between high plasma levels and side effects. Also, since for the specific individual, the metabolism of different tricyclic antidepressants is similar, it may be useful to adjust dosages until a therapeutic one is obtained instead of immediately switching to another medication. Finally, although the usefulness of routine plasma level determination remains to be established, this technique may be indicated in cases of intractable depression and remains an important research tool.", "contents": "Therapeutic implications of tricyclic antidepressant plasma levels. Methodological advances in drug assay techniques and their increasing availability have made the measurement of tricyclic antidepressant plasma levels more frequent and even fashionable. Plasma levels of tricyclics have been correlated with diagnosis, prognosis, clinical response, and side effects. But even in the area most extensively examined, the correlation between plasma level and clinical response, the results have been conflicting. Different studies have suggested that there is no relationship between plasma level and clinical response, as well as positive and negative correlations, and even a curvilinear relationship. On the basis of available evidence, it is impossible to define a therapeutic range of plasma levels that will be applicable to depressed patients as a group. For the moment, the problem of finding a suitable therapeutic dose for the individual patient remains of paramount importance. Studies to date suggest the need to take into consideration genetic factors, previous and present use of other drugs, the possibility that therapeutic failure might be a result of too high as well as too low a dose, as well as the possible relationship between high plasma levels and side effects. Also, since for the specific individual, the metabolism of different tricyclic antidepressants is similar, it may be useful to adjust dosages until a therapeutic one is obtained instead of immediately switching to another medication. Finally, although the usefulness of routine plasma level determination remains to be established, this technique may be indicated in cases of intractable depression and remains an important research tool."} {"id": "PMID:1271050", "title": "Gammahydroxy butyric acid: cardiovascular effects in the rat.", "content": "Gammahydroxybutyric acid (GHBA) 1 g/kg i.p. induced a marked and sustained increase in heart frequency and blood pressure in the rats. These effects of GHBA were abolished by a high spinal transection. In biochemical experiments GHBA in the same dose increased the turnover of brain noradrenaline but decreased the turnover of dopamine. The cardiovascular effects of GHBA are suggested to be of central origin, and possibly involve central noradrenergic mechanisms.", "contents": "Gammahydroxy butyric acid: cardiovascular effects in the rat. Gammahydroxybutyric acid (GHBA) 1 g/kg i.p. induced a marked and sustained increase in heart frequency and blood pressure in the rats. These effects of GHBA were abolished by a high spinal transection. In biochemical experiments GHBA in the same dose increased the turnover of brain noradrenaline but decreased the turnover of dopamine. The cardiovascular effects of GHBA are suggested to be of central origin, and possibly involve central noradrenergic mechanisms."} {"id": "PMID:1271051", "title": "Quantitative changes in number of \"synaptic\" ribbons in rat pinealocytes after orchidectomy and in organ culture.", "content": "A quantitative study of \"synaptic\" ribbons in rat pinealocytes was performed after orchidectomy and in organ culture. Both orchidectomy and culturing the pineal organ caused an increase in number and size of these structures. Present study indicate that microtubular sheaves and/or microtubules may represent precursors of \"synaptic\" ribbons. It is suggested that \"synaptic\" ribbons of rat pinealocytes, far from being phylogenetic relics of no functional significance play a role in the function of the pineal organ. An exact functional interpretation of the \"synaptic\" ribbons, however, is still a matter of conjecture.", "contents": "Quantitative changes in number of \"synaptic\" ribbons in rat pinealocytes after orchidectomy and in organ culture. A quantitative study of \"synaptic\" ribbons in rat pinealocytes was performed after orchidectomy and in organ culture. Both orchidectomy and culturing the pineal organ caused an increase in number and size of these structures. Present study indicate that microtubular sheaves and/or microtubules may represent precursors of \"synaptic\" ribbons. It is suggested that \"synaptic\" ribbons of rat pinealocytes, far from being phylogenetic relics of no functional significance play a role in the function of the pineal organ. An exact functional interpretation of the \"synaptic\" ribbons, however, is still a matter of conjecture."} {"id": "PMID:1271052", "title": "Differential drug effects on dopamine concentrations and rates of turnover in the median eminence, olfactory tubercle and corpus striatum.", "content": "Dopamine synthesis rates were determined in terminals of tuberoinfundibular, mesolimbic and nigrostriatal neuronal systems by observing the decline of dopamine contents in the median eminence, olfactory tubercle and corpus striatum after administration of alpha-methyltyrosine. In control (no drug treatment) animals the rate of synthesis of dopamine was greater in the median eminence than in the other two brain regions. Haloperidol increased and piribedil decreased dopamine turnover in the corpus striatum and olfactory tubercle, but not in the median eminence. Gamma-Butyrolactone increased dopamine concentrations in the olfactory tubercle and striatum without altering the concentration in the median eminence. Thus, the regulatory mechanisms governing the activity of central dopaminergic neurons in the tuberoinfundibular system appear to differ from those in the mesolimbic and nigrostriatal systems.", "contents": "Differential drug effects on dopamine concentrations and rates of turnover in the median eminence, olfactory tubercle and corpus striatum. Dopamine synthesis rates were determined in terminals of tuberoinfundibular, mesolimbic and nigrostriatal neuronal systems by observing the decline of dopamine contents in the median eminence, olfactory tubercle and corpus striatum after administration of alpha-methyltyrosine. In control (no drug treatment) animals the rate of synthesis of dopamine was greater in the median eminence than in the other two brain regions. Haloperidol increased and piribedil decreased dopamine turnover in the corpus striatum and olfactory tubercle, but not in the median eminence. Gamma-Butyrolactone increased dopamine concentrations in the olfactory tubercle and striatum without altering the concentration in the median eminence. Thus, the regulatory mechanisms governing the activity of central dopaminergic neurons in the tuberoinfundibular system appear to differ from those in the mesolimbic and nigrostriatal systems."} {"id": "PMID:1271053", "title": "Effects of denervation and colchicine treatment on the chloride conductance of rat skeletal muscle fibers.", "content": "Membrane potentials, cable parameters, and component resting conductances were measured in extensor digitorum longus (EDL) muscle fibers from adult rats in vitro at 24 degrees C, after 15 to 18 days of denervation by nerve section, and at seven to ten days following epineural injection of 100 to 450 mug of colchicine in the peroneal nerve. The denervated muscles were paralyzed throughout the experimental period, whereas the colchicine-treated preparations showed no clinical paralysis except for the first day or two. The EDL from the untreated side served as a control. Both the denervated and colchicine-treated fibers were depolarized, showed signs of fibrillation, had tetrodotoxin-resistant potentials, and membrane resistance was increased two- to sevenfold. In the denervated fibers, mean chloride conductance GC1 dropped from a control value of 3196 to 596 mumhos/cm2 while mean potassium conductance GK showed a tendency to rise from 260 to 332 muhos/cm2. Colchicine-treated fibers while showing a similar fall in mean GC1 from 2993 to 1066 mumhos/cm2, also showed a significant fall in mean GK from 213 to 116 mumhos/cm2. It was concluded that factors transported by the microtubular system are important for the maintenance of the high resting GC1 of mammalian skeletal muscle fibers.", "contents": "Effects of denervation and colchicine treatment on the chloride conductance of rat skeletal muscle fibers. Membrane potentials, cable parameters, and component resting conductances were measured in extensor digitorum longus (EDL) muscle fibers from adult rats in vitro at 24 degrees C, after 15 to 18 days of denervation by nerve section, and at seven to ten days following epineural injection of 100 to 450 mug of colchicine in the peroneal nerve. The denervated muscles were paralyzed throughout the experimental period, whereas the colchicine-treated preparations showed no clinical paralysis except for the first day or two. The EDL from the untreated side served as a control. Both the denervated and colchicine-treated fibers were depolarized, showed signs of fibrillation, had tetrodotoxin-resistant potentials, and membrane resistance was increased two- to sevenfold. In the denervated fibers, mean chloride conductance GC1 dropped from a control value of 3196 to 596 mumhos/cm2 while mean potassium conductance GK showed a tendency to rise from 260 to 332 muhos/cm2. Colchicine-treated fibers while showing a similar fall in mean GC1 from 2993 to 1066 mumhos/cm2, also showed a significant fall in mean GK from 213 to 116 mumhos/cm2. It was concluded that factors transported by the microtubular system are important for the maintenance of the high resting GC1 of mammalian skeletal muscle fibers."} {"id": "PMID:1271054", "title": "Chloride conductance of denervated gastrocnemius fibers from normal goats.", "content": "Membrane potentials, cable parameters, and component resting ionic conductances of gastrocnemius fibers from normal goats were measured in vitro at six to 32 days following denervation by section of the tibial nerve. Denervated fibers were depolarized an average of 11.6 +/- 1.5 mV (six preparations) from the control mean of 62.1 +/- 1.0 mV (124 fibers) over the period studied. Fibrillation, tetrodotoxin-resistant action potentials, and anode-break excitation were present in the denervated preparations after 13 days. The control cable parameters from 124 fibers (13 preparations) were membrane resistance, 1052 +/- 70 omega-cm2 and membrane capacitance, 6.2 muF/cm2. In denervated fibers membrane resistance increased two to three times in the 13 to 32 day period; membrane capacitance increased about 50% in normal solution at eight to nine, 27-28, and 32 days. Myoplasmic resistivity was assumed to be 112 omega-cm. Measurements were made at 38 degrees C. Component resting conductances were determined from the cable parameters in normal and chloride-free solution. Mean chloride conducantance GC1 and mean potassium conductance GK of control fibers were 776 +/- 49 mumhos/cm2 and 175 +/- 15 mumhos/cm2 (92 fibers), respectively. Following denervation GC1 increased slightly at six to nine days then fell to low values at 16 to 32 days that were close to or indistinguishable from zero. GK increased significantly to 372 +/- 40 mumhos/cm2 and 499 +/- 90 mumhos/cm2 at 16 to 20 and 32 days, respectively. It was concluded from these findings that GC1 and GK of mammalian skeletal muscle are controlled by factors from the nerve and/or muscle action potentials. Goat muscle is different from frog muscle in which GC1 does not change and GK decreases during denervation.", "contents": "Chloride conductance of denervated gastrocnemius fibers from normal goats. Membrane potentials, cable parameters, and component resting ionic conductances of gastrocnemius fibers from normal goats were measured in vitro at six to 32 days following denervation by section of the tibial nerve. Denervated fibers were depolarized an average of 11.6 +/- 1.5 mV (six preparations) from the control mean of 62.1 +/- 1.0 mV (124 fibers) over the period studied. Fibrillation, tetrodotoxin-resistant action potentials, and anode-break excitation were present in the denervated preparations after 13 days. The control cable parameters from 124 fibers (13 preparations) were membrane resistance, 1052 +/- 70 omega-cm2 and membrane capacitance, 6.2 muF/cm2. In denervated fibers membrane resistance increased two to three times in the 13 to 32 day period; membrane capacitance increased about 50% in normal solution at eight to nine, 27-28, and 32 days. Myoplasmic resistivity was assumed to be 112 omega-cm. Measurements were made at 38 degrees C. Component resting conductances were determined from the cable parameters in normal and chloride-free solution. Mean chloride conducantance GC1 and mean potassium conductance GK of control fibers were 776 +/- 49 mumhos/cm2 and 175 +/- 15 mumhos/cm2 (92 fibers), respectively. Following denervation GC1 increased slightly at six to nine days then fell to low values at 16 to 32 days that were close to or indistinguishable from zero. GK increased significantly to 372 +/- 40 mumhos/cm2 and 499 +/- 90 mumhos/cm2 at 16 to 20 and 32 days, respectively. It was concluded from these findings that GC1 and GK of mammalian skeletal muscle are controlled by factors from the nerve and/or muscle action potentials. Goat muscle is different from frog muscle in which GC1 does not change and GK decreases during denervation."} {"id": "PMID:1271055", "title": "Anatomical basis for an apparent paradox concerning conduction velocities of two identified axons in Aplysia.", "content": "Larger axons usually have faster conduction velocities, lower thresholds, and larger extracellular action potentials than smaller axons. However, it has been shown that the largest fiber, R2, in the right pleurovisceral connective of the marine mollusc, Aplysia, has a higher threshold and a slower conduction velocity than does the smaller axon of cell RI, even though the amplitude of R2's spike is larger than R1's spike. One explanation of this apparent parodox is that the two axons have different \"intrinsic membrane and axoplasmic constants\" (Goldman, L. (1961), J. Cell Comp. Physiol. 57: 185-191). However, the deep infolding of R2's axonal membrane suggested that differences in the shape of the two axons might also account for the paradox. Accordingly, we measured the conduction velocities of the two axons and then examined the same axons in the electron microscope in order to measure their volumes and surface areas. Our morphological observations indicate that the extensive infolding of surface membrane causes R2 to have a smaller volume to surface area ratio than R1. Thus, since conduction velocity is proportional to the square root of the volume to surface area ratio (Hodgkin, A.L. (1954), J. Physiol. 125: 221-224), it is predictable that the smaller axon would have a faster conduction velocity. The results suggest that the paradoxical conduction velocities can be explained largely as resulting from differences in the shapes of the two axons. However, certain discrepancies between the measured and the predicted values suggest that other factors are contributing as well.", "contents": "Anatomical basis for an apparent paradox concerning conduction velocities of two identified axons in Aplysia. Larger axons usually have faster conduction velocities, lower thresholds, and larger extracellular action potentials than smaller axons. However, it has been shown that the largest fiber, R2, in the right pleurovisceral connective of the marine mollusc, Aplysia, has a higher threshold and a slower conduction velocity than does the smaller axon of cell RI, even though the amplitude of R2's spike is larger than R1's spike. One explanation of this apparent parodox is that the two axons have different \"intrinsic membrane and axoplasmic constants\" (Goldman, L. (1961), J. Cell Comp. Physiol. 57: 185-191). However, the deep infolding of R2's axonal membrane suggested that differences in the shape of the two axons might also account for the paradox. Accordingly, we measured the conduction velocities of the two axons and then examined the same axons in the electron microscope in order to measure their volumes and surface areas. Our morphological observations indicate that the extensive infolding of surface membrane causes R2 to have a smaller volume to surface area ratio than R1. Thus, since conduction velocity is proportional to the square root of the volume to surface area ratio (Hodgkin, A.L. (1954), J. Physiol. 125: 221-224), it is predictable that the smaller axon would have a faster conduction velocity. The results suggest that the paradoxical conduction velocities can be explained largely as resulting from differences in the shapes of the two axons. However, certain discrepancies between the measured and the predicted values suggest that other factors are contributing as well."} {"id": "PMID:1271056", "title": "Cytophotometric identification of tetraploid Purkinje cells in young and aged rats.", "content": "DNA content of cerebellar basket and Purkinje cells of four month, one year, and two year old albino rats was determined by Feulgen cytophotometry. DNA content per nucleus remained essentially constant during aging although there was a slight shift to lower Feulgen-DNA values occurring in the one year age group. Purkinje cells of all three age groups were found to contain tetraploid amounts of DNA as compared to diploid basket cells.", "contents": "Cytophotometric identification of tetraploid Purkinje cells in young and aged rats. DNA content of cerebellar basket and Purkinje cells of four month, one year, and two year old albino rats was determined by Feulgen cytophotometry. DNA content per nucleus remained essentially constant during aging although there was a slight shift to lower Feulgen-DNA values occurring in the one year age group. Purkinje cells of all three age groups were found to contain tetraploid amounts of DNA as compared to diploid basket cells."} {"id": "PMID:1271057", "title": "Electrical properties and structure of the frog arachnoid membrane.", "content": "We have used an in vitro preparation of the frog arachnoid membrane to study the role of this membrane in the maintenance of the \"blood-cerebrospinal fluid (csf) barrier\". Electron microscopy showed that the membrane was made up of 10-15 layers of flat epithelial cells joined together by numerous cell junctions. The electrical resistance of the preparation was about 2000 ohms cm2. The steady-state transmural potential difference (pd) ranged up to 45 mV, csf positive, and this eliminated by either the addition of ouabain to the csf, or by replacing the NaC1 with TEA C1. The pd across the membrane increased when bicarbonate was added to the external bathing solutions. We conclude that this pd is due to the active transport of sodium from the subural fluid to the csf. In some preparations the transmural pd was reversed, i.e., csf negative, and this was also abolished by the addition of ouabain to the csf, or by replacing chloride with isethionate. We conclude that this pd is related to active chloride transport. These, and other experiments, lead us to the conclusion that the arachnois membrane is involved in the production of the cerebrospinal fluid and the maintenance of the blood-cerebrospinal fluid barrier.", "contents": "Electrical properties and structure of the frog arachnoid membrane. We have used an in vitro preparation of the frog arachnoid membrane to study the role of this membrane in the maintenance of the \"blood-cerebrospinal fluid (csf) barrier\". Electron microscopy showed that the membrane was made up of 10-15 layers of flat epithelial cells joined together by numerous cell junctions. The electrical resistance of the preparation was about 2000 ohms cm2. The steady-state transmural potential difference (pd) ranged up to 45 mV, csf positive, and this eliminated by either the addition of ouabain to the csf, or by replacing the NaC1 with TEA C1. The pd across the membrane increased when bicarbonate was added to the external bathing solutions. We conclude that this pd is due to the active transport of sodium from the subural fluid to the csf. In some preparations the transmural pd was reversed, i.e., csf negative, and this was also abolished by the addition of ouabain to the csf, or by replacing chloride with isethionate. We conclude that this pd is related to active chloride transport. These, and other experiments, lead us to the conclusion that the arachnois membrane is involved in the production of the cerebrospinal fluid and the maintenance of the blood-cerebrospinal fluid barrier."} {"id": "PMID:1271058", "title": "A long-lasting birefringence change recorded from a tetanically stimulated squid giant axon.", "content": "A long-lasting birefringence change (the delayed response) was found to be produced in a tetanically stimulated squid giant axon. The change was independent of the concurrent membrane potential change, summated on repetitive stimulation, and always had a sign representing a decrease in resting birefringence. The axons was placed between a polarizer and an analyzer with their polarizing axes crossed, making an angle of 45 degrees with the longitudinal direction of the axon. The light beam that passed through the axon and the other optical elements was received by a photodiode. The change in light intensity evoked by repetitive stimulation was composed of brief initial responses, which took place in response to individual stimuli, and a delayed response, which developed gradually and lasted for several hundred msec. It was necessary to differentiate the effect of birefringence change from that of turbidity change. Formulas were derived on the assumption that the optical properties of the axon could be represented by a model of a uniaxial crystal that was not only birefringent but also dichroic, its extinction coefficients and the angle of retardation being changed independently on excitation. Calculations with them yielded the resting retardation, which agreed well with those obtained by the Senarmont's method, and the change in birefringence, which agreed well with the other calculated value derived from experiments using a quarter-wave plate. The results of the calculation confirmed the existence of the long-lasting birefringence change in the tetanically stimulated axon.", "contents": "A long-lasting birefringence change recorded from a tetanically stimulated squid giant axon. A long-lasting birefringence change (the delayed response) was found to be produced in a tetanically stimulated squid giant axon. The change was independent of the concurrent membrane potential change, summated on repetitive stimulation, and always had a sign representing a decrease in resting birefringence. The axons was placed between a polarizer and an analyzer with their polarizing axes crossed, making an angle of 45 degrees with the longitudinal direction of the axon. The light beam that passed through the axon and the other optical elements was received by a photodiode. The change in light intensity evoked by repetitive stimulation was composed of brief initial responses, which took place in response to individual stimuli, and a delayed response, which developed gradually and lasted for several hundred msec. It was necessary to differentiate the effect of birefringence change from that of turbidity change. Formulas were derived on the assumption that the optical properties of the axon could be represented by a model of a uniaxial crystal that was not only birefringent but also dichroic, its extinction coefficients and the angle of retardation being changed independently on excitation. Calculations with them yielded the resting retardation, which agreed well with those obtained by the Senarmont's method, and the change in birefringence, which agreed well with the other calculated value derived from experiments using a quarter-wave plate. The results of the calculation confirmed the existence of the long-lasting birefringence change in the tetanically stimulated axon."} {"id": "PMID:1271079", "title": "Subarachnoid block and enlargement of the spinal canal in hypertrophic neuritis.", "content": "A case of Dejerine-Sottas hypertrophic neuritis is reported. The patient, a 45-year-old male, suffered from chronic hypertrophic polyneuropathy, abnormal pupils, fasciculations, tremor, back pain, impotence, sphincter disorders, cramps, and lightning pains in the lower extremities. Besides extensive subarachnoid block, there was X-ray evidence of enlargement of the bony spinal canal with scalloping of the lumbar vertebrae. Surgical exploration showed these abnormalities to be due to extreme hypertrophy of the cauda equina. Histologic findings in peripheral nerve and lumbar root biopsies were typical of hypertrophic neuropathy of the onion bulb type. Vertebral changes secondary to hypertrophied nerve roots appear not to have been described before in hypertrophic neuritis; however, knowledge of their possible occurrence may be of practical importance in the management of similar future cases. A simple way of visualizing enlarged peripheral nerves is briefly described.", "contents": "Subarachnoid block and enlargement of the spinal canal in hypertrophic neuritis. A case of Dejerine-Sottas hypertrophic neuritis is reported. The patient, a 45-year-old male, suffered from chronic hypertrophic polyneuropathy, abnormal pupils, fasciculations, tremor, back pain, impotence, sphincter disorders, cramps, and lightning pains in the lower extremities. Besides extensive subarachnoid block, there was X-ray evidence of enlargement of the bony spinal canal with scalloping of the lumbar vertebrae. Surgical exploration showed these abnormalities to be due to extreme hypertrophy of the cauda equina. Histologic findings in peripheral nerve and lumbar root biopsies were typical of hypertrophic neuropathy of the onion bulb type. Vertebral changes secondary to hypertrophied nerve roots appear not to have been described before in hypertrophic neuritis; however, knowledge of their possible occurrence may be of practical importance in the management of similar future cases. A simple way of visualizing enlarged peripheral nerves is briefly described."} {"id": "PMID:1271080", "title": "[Hereditary spongiform dystrophy in young children (Canavan: van Bogaert-Bertrand)].", "content": "Hereditary spongiform dystrophy in young children is characterised by macrocephaly with spasticity, convulsions and ultimately a decerebrate state and diffuse electroencephalographic changes. Histological examination of the brain remains essential for its diagnosis. A review of the ultrastructural studies reported by various authors complements the findings obtained by conventional histology. We have thus endeavoured to determine whether van Bogaert-Bertrand's disease is to be considered as congenital or acquired. The anatomical findings in 3 cases together with the descriptions of other authors lead us to the following conclusions: -that the spongiform changes may be due to an osmolar disequilibrium in which the ATPase-Na/K relation with mitochondrial abnormalities is yet unclear. -that the constant finding of Alzheimer type II cells is certainly an indication of intra-astrocytic malfunction. -that the oedema blocks both myelin synthesis and its coiling into lamellae. Case 1, which showed a long survival compared to others described (about 4 years), enabled us to study terminal lesions. Sub-cortical zones, in both cerebrum and cerebellum, contained neither myelin nor spongiform cavities, but, on the other hand, showed a compact glio-fibrillosis with large vesicles and oligodendroglia of increased density. We have interpreted these lesions, progressively replaced by spongiosis deeper in the cortex, as evidence of retracted scar tissue. Differences found between cerebral weights seem to confirm this hypothesis.", "contents": "[Hereditary spongiform dystrophy in young children (Canavan: van Bogaert-Bertrand)]. Hereditary spongiform dystrophy in young children is characterised by macrocephaly with spasticity, convulsions and ultimately a decerebrate state and diffuse electroencephalographic changes. Histological examination of the brain remains essential for its diagnosis. A review of the ultrastructural studies reported by various authors complements the findings obtained by conventional histology. We have thus endeavoured to determine whether van Bogaert-Bertrand's disease is to be considered as congenital or acquired. The anatomical findings in 3 cases together with the descriptions of other authors lead us to the following conclusions: -that the spongiform changes may be due to an osmolar disequilibrium in which the ATPase-Na/K relation with mitochondrial abnormalities is yet unclear. -that the constant finding of Alzheimer type II cells is certainly an indication of intra-astrocytic malfunction. -that the oedema blocks both myelin synthesis and its coiling into lamellae. Case 1, which showed a long survival compared to others described (about 4 years), enabled us to study terminal lesions. Sub-cortical zones, in both cerebrum and cerebellum, contained neither myelin nor spongiform cavities, but, on the other hand, showed a compact glio-fibrillosis with large vesicles and oligodendroglia of increased density. We have interpreted these lesions, progressively replaced by spongiosis deeper in the cortex, as evidence of retracted scar tissue. Differences found between cerebral weights seem to confirm this hypothesis."} {"id": "PMID:1271081", "title": "The neuropathic factor in the aetiology of diabetic foot ulcers.", "content": "The nature and severity of changes due to peripheral neuropathy has been assessed clinically and electrophysiologically in 39 diabetic patients, 23 of whom had penetrating ulcers on the sole of the foot. Patients suffering from diabetic foot ulcers were found to have sensory loss to pin prick in the feet more frequently than \"controls\". The electrophysiological measurements confirmed the severity of the neuropathy with absent sural nerve action potentials in 95% of the ulcer patients and inexcitability of small foot muscles in 40%. Weakness of small foot muscles due to neuropathy is thought to underlie the foot deformity that leads to maldistribution of weight bearing, and subsequent pressure necrosis of analgesic skin.", "contents": "The neuropathic factor in the aetiology of diabetic foot ulcers. The nature and severity of changes due to peripheral neuropathy has been assessed clinically and electrophysiologically in 39 diabetic patients, 23 of whom had penetrating ulcers on the sole of the foot. Patients suffering from diabetic foot ulcers were found to have sensory loss to pin prick in the feet more frequently than \"controls\". The electrophysiological measurements confirmed the severity of the neuropathy with absent sural nerve action potentials in 95% of the ulcer patients and inexcitability of small foot muscles in 40%. Weakness of small foot muscles due to neuropathy is thought to underlie the foot deformity that leads to maldistribution of weight bearing, and subsequent pressure necrosis of analgesic skin."} {"id": "PMID:1271082", "title": "[Myasthenia, thymoma and hypophyseal tumor associated with heterogenous adenomatous proliferation and ganglioneuroma of the sella turcica].", "content": "The authors report a case of myasthenia gravis in which a tumour of the sella turcica, without clinical symptoms, was discovered on X-ray examination of the skull and was removed with success. Histological study showed endocrine and neural type cells with cells of intermediate type. Subsequent thoracic surgery was performed with removal of a thymoma which was not visible on X-ray examination of the chest. The first operation on the sella turcica had no effect on the myasthenia but after the second on the thymoma a definite improvement was noted. The association of myasthenia, thymoma and ganglioneuroma of the sella turcica is unknown. In order to explain this, the authors hypothesize a common origin in the neural crests of both tumours.", "contents": "[Myasthenia, thymoma and hypophyseal tumor associated with heterogenous adenomatous proliferation and ganglioneuroma of the sella turcica]. The authors report a case of myasthenia gravis in which a tumour of the sella turcica, without clinical symptoms, was discovered on X-ray examination of the skull and was removed with success. Histological study showed endocrine and neural type cells with cells of intermediate type. Subsequent thoracic surgery was performed with removal of a thymoma which was not visible on X-ray examination of the chest. The first operation on the sella turcica had no effect on the myasthenia but after the second on the thymoma a definite improvement was noted. The association of myasthenia, thymoma and ganglioneuroma of the sella turcica is unknown. In order to explain this, the authors hypothesize a common origin in the neural crests of both tumours."} {"id": "PMID:1271083", "title": "Cerebro-hepato-renal syndrome. Report of a case with histochemical and ultrastructural observations.", "content": "A new case of the cerebro-hepato-renal syndrome is being reported. The neuropathologic changes consisted of developmental abnormalities of cerebral and cerebellar cortex and of the inferior olives. In addition, there were metabolic changes in the central nervous system, indicated by an accumulation of lipid within histiocytes of free in gray and white matter, deficiency in myelination and gliosis of the white matter, and marked proliferation of protoplasmic astrocytes in the gray matter. A unique feature of this case was the presence of numerous clusters of lipid-filled macrophages and occasional cholesterol crystals in the molecular layer of the cerebellum. The histochemical reactions and ultrastructural appearances of the lipid deposits are suggestive of accumulation of several different types of lipids.", "contents": "Cerebro-hepato-renal syndrome. Report of a case with histochemical and ultrastructural observations. A new case of the cerebro-hepato-renal syndrome is being reported. The neuropathologic changes consisted of developmental abnormalities of cerebral and cerebellar cortex and of the inferior olives. In addition, there were metabolic changes in the central nervous system, indicated by an accumulation of lipid within histiocytes of free in gray and white matter, deficiency in myelination and gliosis of the white matter, and marked proliferation of protoplasmic astrocytes in the gray matter. A unique feature of this case was the presence of numerous clusters of lipid-filled macrophages and occasional cholesterol crystals in the molecular layer of the cerebellum. The histochemical reactions and ultrastructural appearances of the lipid deposits are suggestive of accumulation of several different types of lipids."} {"id": "PMID:1271084", "title": "Neonatal neuronal loss in rat superior cervical ganglia: retrograde effects on developing preganglionic axons and Schwann cells.", "content": "Beginning prenatally and during the first week after birth, there is normally a loss of axons in rat cervical sympathetic trunk. To test the hypothesis that this spontaneous axonal loss represents a natural process whereby an excessive number of immature preganglionic axons in the cervical sympathetic trunk adapts to the neuronal population in the superior cervical ganglion, the number of nerve cells in the superior cervical ganglion was reduced in newborn rats by administration of nerve growth factor antiserum, 6-hydroxy-dopamine or postganglionic anxotomy. Quantitative ultrastructural studies of these animals at later stages of development revealed that, with each method, the number of preganglionic axons and Schwann cells was reduced to nearly one-third of normal. These findings indicate that the superior cervical ganglion plays an important role in the development of the cervical sympathetic trunk. Removal of ganglionic cells causes a retrograde loss of preganglionic fibres. This process probably represents an exaggeration of the normal mechanism for elimination of redundant axons. Because the changes in axonal numbers are associated with similar reductions in the number of Schwann cells, it can also be concluded that postnatal Schwann cell proliferation is influenced by axonal populations.", "contents": "Neonatal neuronal loss in rat superior cervical ganglia: retrograde effects on developing preganglionic axons and Schwann cells. Beginning prenatally and during the first week after birth, there is normally a loss of axons in rat cervical sympathetic trunk. To test the hypothesis that this spontaneous axonal loss represents a natural process whereby an excessive number of immature preganglionic axons in the cervical sympathetic trunk adapts to the neuronal population in the superior cervical ganglion, the number of nerve cells in the superior cervical ganglion was reduced in newborn rats by administration of nerve growth factor antiserum, 6-hydroxy-dopamine or postganglionic anxotomy. Quantitative ultrastructural studies of these animals at later stages of development revealed that, with each method, the number of preganglionic axons and Schwann cells was reduced to nearly one-third of normal. These findings indicate that the superior cervical ganglion plays an important role in the development of the cervical sympathetic trunk. Removal of ganglionic cells causes a retrograde loss of preganglionic fibres. This process probably represents an exaggeration of the normal mechanism for elimination of redundant axons. Because the changes in axonal numbers are associated with similar reductions in the number of Schwann cells, it can also be concluded that postnatal Schwann cell proliferation is influenced by axonal populations."} {"id": "PMID:1271085", "title": "The altrastructure of Auerbach's plexus in the guinea-pig. I. Neuronal elements.", "content": "The ultrastructural features of nerve cell bodies and axon profiles within Auerbach's plexus in the stomach, ileum, caecum and colon of the guinea-pig have been examined. Nerve cell bodies have been tentatively classified into nine different types according to their size, distribution of organelles, location and relationship to satellite cells. Except for cell size, no attempt has been made to correlate ultrastructual with light microscopical observations. On the basis of vesicular size, shape and content, eight morphologically distinct types of axon profile have been identified as well as two profile types which are thought to reflect different physiological conditions. The axons contained various populations of small, mostly granular vesicles; small, round agranular vesicles; small, flattened vesicles; large flattened or elongated vesicles; and three types of large vesicle with granular contents distinguished by size. Some correlation between types of axon profile and two types of nerve cell body was recognized. However, more than one type of axon profile usually formed synapses with one type of cell body, and a precise correlation was not determined.", "contents": "The altrastructure of Auerbach's plexus in the guinea-pig. I. Neuronal elements. The ultrastructural features of nerve cell bodies and axon profiles within Auerbach's plexus in the stomach, ileum, caecum and colon of the guinea-pig have been examined. Nerve cell bodies have been tentatively classified into nine different types according to their size, distribution of organelles, location and relationship to satellite cells. Except for cell size, no attempt has been made to correlate ultrastructual with light microscopical observations. On the basis of vesicular size, shape and content, eight morphologically distinct types of axon profile have been identified as well as two profile types which are thought to reflect different physiological conditions. The axons contained various populations of small, mostly granular vesicles; small, round agranular vesicles; small, flattened vesicles; large flattened or elongated vesicles; and three types of large vesicle with granular contents distinguished by size. Some correlation between types of axon profile and two types of nerve cell body was recognized. However, more than one type of axon profile usually formed synapses with one type of cell body, and a precise correlation was not determined."} {"id": "PMID:1271086", "title": "The ultrastructure of Auerbach's plexus in the guinea-pig. II. Non-neuronal elements.", "content": "The ultrastructural features of non-neuronal cells associated with Auerbach's plexus in the stomach, ileum and colon of the guinea-pig have been examined. Apart from Schwann, mast and interstitial or fibroblast-like cells, two other cell types are described that do not appear to have been reported previously. Of these two cell types, one was found external, but close to, the plexus and contained large granular vesicles. The other cell type contained numerous glycogen-like granules, was situated close to or within axon bundles and had processes that extended within and peripheral to nerve bundles as well as being close to smooth muscle cells. Although axon varicosities were opposed to both the processes and cell body of the second type of cell, synaptic-like contacts were not observed.", "contents": "The ultrastructure of Auerbach's plexus in the guinea-pig. II. Non-neuronal elements. The ultrastructural features of non-neuronal cells associated with Auerbach's plexus in the stomach, ileum and colon of the guinea-pig have been examined. Apart from Schwann, mast and interstitial or fibroblast-like cells, two other cell types are described that do not appear to have been reported previously. Of these two cell types, one was found external, but close to, the plexus and contained large granular vesicles. The other cell type contained numerous glycogen-like granules, was situated close to or within axon bundles and had processes that extended within and peripheral to nerve bundles as well as being close to smooth muscle cells. Although axon varicosities were opposed to both the processes and cell body of the second type of cell, synaptic-like contacts were not observed."} {"id": "PMID:1271087", "title": "Organization of crustacean neuropil. I. Patterns of synaptic connections in lobster stomatogastric ganglion.", "content": "The stomatogastric ganglion of the lobster consists of about thiry neurons, mainly large monopolar cells, which have been well characterized physiologically. This paper presents an anatomical description of this ganglion, emphasizing synaptic connections in the neuropil. The neuron cell bodies are located on the dorsal surface of the ganglion. They send processes into the underlying neuropil mass. The neuropil is differentiated into two regions: a core of coarse neuropil consists of large heavily ensheathed processes; a surrounding region of fine-textured synaptic neuropil consists of smaller unsheather processes. Synapses are found only in synaptic neuropil, not in the core of coarse neuropil. Synaptic contacts, about one million in the entire neuropil, are easily recognized by a set of criteria including presynaptic vesicles and pre- and postsynaptic membrane specializations. Most synaptic contacts invole at least three neural processes, usually one pre- and two postsynaptic elements. Synapses are clustered onto irregular swellings or varicosities on neural processes. These varicosities make both pre- and postsynaptic contacts. Three differenty types of presynaptic profile are recognized. Pyloric dilator, ventricular dilator and lateral posterior gastric neurons belong to type A with clear irregular synaptic vesicles. Lateral pyloric, pyloric, anterior median and dorsal gastric neurons belong to type B with larger clear round vesicles. Many unidentified fibres, presumably stomatogastric nerve afferents, blong to type C with both small clear irregular vesicles and also large dense-core vesicles. The synaptic vesicle types are tentatively correlated with neurotransmitter: type A with acetylcholine, type B with an unknown transmitter, possibly glutamate, and type C with dopamine. The distribution of synaptic contacts on the processes of identified neurons reconstructed from serial section is presented in the following paper.", "contents": "Organization of crustacean neuropil. I. Patterns of synaptic connections in lobster stomatogastric ganglion. The stomatogastric ganglion of the lobster consists of about thiry neurons, mainly large monopolar cells, which have been well characterized physiologically. This paper presents an anatomical description of this ganglion, emphasizing synaptic connections in the neuropil. The neuron cell bodies are located on the dorsal surface of the ganglion. They send processes into the underlying neuropil mass. The neuropil is differentiated into two regions: a core of coarse neuropil consists of large heavily ensheathed processes; a surrounding region of fine-textured synaptic neuropil consists of smaller unsheather processes. Synapses are found only in synaptic neuropil, not in the core of coarse neuropil. Synaptic contacts, about one million in the entire neuropil, are easily recognized by a set of criteria including presynaptic vesicles and pre- and postsynaptic membrane specializations. Most synaptic contacts invole at least three neural processes, usually one pre- and two postsynaptic elements. Synapses are clustered onto irregular swellings or varicosities on neural processes. These varicosities make both pre- and postsynaptic contacts. Three differenty types of presynaptic profile are recognized. Pyloric dilator, ventricular dilator and lateral posterior gastric neurons belong to type A with clear irregular synaptic vesicles. Lateral pyloric, pyloric, anterior median and dorsal gastric neurons belong to type B with larger clear round vesicles. Many unidentified fibres, presumably stomatogastric nerve afferents, blong to type C with both small clear irregular vesicles and also large dense-core vesicles. The synaptic vesicle types are tentatively correlated with neurotransmitter: type A with acetylcholine, type B with an unknown transmitter, possibly glutamate, and type C with dopamine. The distribution of synaptic contacts on the processes of identified neurons reconstructed from serial section is presented in the following paper."} {"id": "PMID:1271088", "title": "Carbohydrates as potential diagnostic tracers for brain tumors.", "content": "Currently available diagnostic tracers for brain tumors are not specific. Tumor-specific tracers would improve the detection of brain tumors by gamma encephalography. Glucose is an important substrate for tumor metabolism and is known to be taken up in large amounts. The authors have studied five labeled carbohydrates in an attempt to find a tumor-specific tracer: three were tritiated (L-galactose-1-3H, L-fucose-3H, and 4,6-dideoxy-xylo-hexose-3H) and two were radioiodinated (methyl-6-125I-6-deoxy-D-glucoside and 6-125I-6-deoxy-D-glucose). The uptake of these tracers by a transplantable mouse ependymoblastoma after intravenous injection was determined by liquid and well scintillation counting. The highest tumor-to-brain ratio was 7.1 to 1 for the tritiated tracers and 6.2 to 1 for the radioiodinated tracers. Although these ratios are not high enough for gamma encephalography, one of the iodinated tracers may be useful for enhancement of contrast in computerized axial tomography.", "contents": "Carbohydrates as potential diagnostic tracers for brain tumors. Currently available diagnostic tracers for brain tumors are not specific. Tumor-specific tracers would improve the detection of brain tumors by gamma encephalography. Glucose is an important substrate for tumor metabolism and is known to be taken up in large amounts. The authors have studied five labeled carbohydrates in an attempt to find a tumor-specific tracer: three were tritiated (L-galactose-1-3H, L-fucose-3H, and 4,6-dideoxy-xylo-hexose-3H) and two were radioiodinated (methyl-6-125I-6-deoxy-D-glucoside and 6-125I-6-deoxy-D-glucose). The uptake of these tracers by a transplantable mouse ependymoblastoma after intravenous injection was determined by liquid and well scintillation counting. The highest tumor-to-brain ratio was 7.1 to 1 for the tritiated tracers and 6.2 to 1 for the radioiodinated tracers. Although these ratios are not high enough for gamma encephalography, one of the iodinated tracers may be useful for enhancement of contrast in computerized axial tomography."} {"id": "PMID:1271089", "title": "Body position and cerebrospinal fluid pressure. Part 1: clinical studies on the effect of rapid postural changes.", "content": "Cerebrospinal fluid (CSF) pressure was recorded in 149 patients and arterial blood pressure (BP) in 11 patients while moving between lateral and sitting positions. Rapid tilting initiated waves in BP and CSF filling pressure. The postural CSF pressure wave manifested itself either as a transient or as a stationary wave similar to a plateau wave. When patients sat up, transient waves had amplitudes up to 550 and stationary waves up to 1000 mm H2O. When they lay down, transient waves had amplitudes up to 800 mm H2O. Stationary waves were found only among patients with elevated intracranial pressure and a diseased brain. The waves were mainly caused by changes in cerebral blood volume probably reflecting the postural BP wave and brain autoregulation. Most patients with stationary and large transient waves also manifested clinical symptoms. These symptoms were aggravated when a craniospinal block developed in the sitting position, and were reduced or avoided when the tilting was performed slowly over 2 to 3 minutes.", "contents": "Body position and cerebrospinal fluid pressure. Part 1: clinical studies on the effect of rapid postural changes. Cerebrospinal fluid (CSF) pressure was recorded in 149 patients and arterial blood pressure (BP) in 11 patients while moving between lateral and sitting positions. Rapid tilting initiated waves in BP and CSF filling pressure. The postural CSF pressure wave manifested itself either as a transient or as a stationary wave similar to a plateau wave. When patients sat up, transient waves had amplitudes up to 550 and stationary waves up to 1000 mm H2O. When they lay down, transient waves had amplitudes up to 800 mm H2O. Stationary waves were found only among patients with elevated intracranial pressure and a diseased brain. The waves were mainly caused by changes in cerebral blood volume probably reflecting the postural BP wave and brain autoregulation. Most patients with stationary and large transient waves also manifested clinical symptoms. These symptoms were aggravated when a craniospinal block developed in the sitting position, and were reduced or avoided when the tilting was performed slowly over 2 to 3 minutes."} {"id": "PMID:1271090", "title": "Body position and cerebrospinal fluid pressure. Part 2: clinical studies on orthostatic pressure and the hydrostatic indifferent point.", "content": "Lumbar cerebrospinal fluid (CSF) pressure was recorded in 116 adult neurosurgical patients in the lateral and sitting positions. The level of zero CSF pressure while in the sitting position (ZPS) and hydrostatic indifferent point (HIP) for lateral and sitting positions were determined and referred to the craniospinal axis. In control patients ZPS was located mainly at the upper cervical region, and showed nearly the same variation and frequency distribution as CSF pressure in the lateral position when efforts were made to reduce sources of error and there was no orthostatic change in CSF filling pressure. Under these circumstances ZPS may be used as a variable comparable from one subject to another. In control patients the HIP was located between C-6 and T-5. In 25 hydrocephalic patients, shunting resulted in a mean caudal shift of ZPS of 244 mm, and a mean pressure fall of 126 mm H2O in the lateral position. This difference was due to a caudal shift of HIP on shunting. A caudally located ZPS was found in patients with complete cervical subarachnoid block. Prevention and treatment of CSF leakage cranial to HIP is discussed.", "contents": "Body position and cerebrospinal fluid pressure. Part 2: clinical studies on orthostatic pressure and the hydrostatic indifferent point. Lumbar cerebrospinal fluid (CSF) pressure was recorded in 116 adult neurosurgical patients in the lateral and sitting positions. The level of zero CSF pressure while in the sitting position (ZPS) and hydrostatic indifferent point (HIP) for lateral and sitting positions were determined and referred to the craniospinal axis. In control patients ZPS was located mainly at the upper cervical region, and showed nearly the same variation and frequency distribution as CSF pressure in the lateral position when efforts were made to reduce sources of error and there was no orthostatic change in CSF filling pressure. Under these circumstances ZPS may be used as a variable comparable from one subject to another. In control patients the HIP was located between C-6 and T-5. In 25 hydrocephalic patients, shunting resulted in a mean caudal shift of ZPS of 244 mm, and a mean pressure fall of 126 mm H2O in the lateral position. This difference was due to a caudal shift of HIP on shunting. A caudally located ZPS was found in patients with complete cervical subarachnoid block. Prevention and treatment of CSF leakage cranial to HIP is discussed."} {"id": "PMID:1271091", "title": "Microvascular bypass surgery. Part 1: anatomical studies.", "content": "Microvascular anatomical studies were performed to ascertain the most suitable cortical vessel for extracranial-intracranial arterial bypass (EIAB). The three most commonly used cortical areas (the tip of the frontal lobe, the tip of the temporal lobe, and the area at the angular gyrus) were examined in detail. Because of their accessiblity and size, the cortical arteries in the area of the angular gyrus offer the most suitable location for creating an EIAB.", "contents": "Microvascular bypass surgery. Part 1: anatomical studies. Microvascular anatomical studies were performed to ascertain the most suitable cortical vessel for extracranial-intracranial arterial bypass (EIAB). The three most commonly used cortical areas (the tip of the frontal lobe, the tip of the temporal lobe, and the area at the angular gyrus) were examined in detail. Because of their accessiblity and size, the cortical arteries in the area of the angular gyrus offer the most suitable location for creating an EIAB."} {"id": "PMID:1271092", "title": "Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury.", "content": "Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Ca++), magnesium (Mg++), and chloride (C1-) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca++ concentration on Days 3, 9, 11, 13, and 15, elevation in K+ concentration on Days 9 and 11 and decline in C1- levels on the first day. The CSF K+ increase probably reflected cellular loss of K+ from damaged tissue whereas the Ca++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury.", "contents": "Cerebrospinal fluid lactate and electrolyte levels following experimental spinal cord injury. Cerebrospinal fluid (CSF) lactate, sodium (Na+), potassium (K+), calcium (Ca++), magnesium (Mg++), and chloride (C1-) levels were determined for 17 to 21 days following experimental spinal cord compression in cats. Laminectomies were performed at L-2 under general anesthesia with aseptic techniques. Paraplegia was produced by applying a 170-gm weight transdurally for 5 minutes. Significant increases in CSF lactate levels were observed on the first through ninth days post injury with peak levels (50% above normal) occurring at Day 5. The only significant postinjury CSF electrolyte changes were elevation in Ca++ concentration on Days 3, 9, 11, 13, and 15, elevation in K+ concentration on Days 9 and 11 and decline in C1- levels on the first day. The CSF K+ increase probably reflected cellular loss of K+ from damaged tissue whereas the Ca++ rise may have resulted from increased CSF protein levels. The prolonged elevation of CSF lactate indicates that tissue hypoxia plays a role in spinal cord compression paralysis, and that there is a continuing hypoxia of metabolically active spinal cord tissue for several days post injury."} {"id": "PMID:1271093", "title": "Comparative study of the pressure of various aneurysm clips.", "content": "Comparative study of the pressure and the resistance to slippage of several aneurysm clips was done. Knowledge of the physical characteristics of various clips, such as the pressure, maximum opening angle, and width and thickness of the blade is essential for their proper use.", "contents": "Comparative study of the pressure of various aneurysm clips. Comparative study of the pressure and the resistance to slippage of several aneurysm clips was done. Knowledge of the physical characteristics of various clips, such as the pressure, maximum opening angle, and width and thickness of the blade is essential for their proper use."} {"id": "PMID:1271094", "title": "Postirradiation necrosis of the temporal lobe presenting as a glioma. Case report.", "content": "A patient is reported who presented with manifestations of a space-occupying lesion in the left temporal lobe thought to be a metastasis, but on radiological examination and surgical exploration appeared to be a diffuse infiltrative glioma. Some 21 months earlier he had received a course of fast neutron therapy to a carcinoma of the left parotid gland. Diagnosis by microscopic examination revealed changes characteristic of delayed radiation necrosis.", "contents": "Postirradiation necrosis of the temporal lobe presenting as a glioma. Case report. A patient is reported who presented with manifestations of a space-occupying lesion in the left temporal lobe thought to be a metastasis, but on radiological examination and surgical exploration appeared to be a diffuse infiltrative glioma. Some 21 months earlier he had received a course of fast neutron therapy to a carcinoma of the left parotid gland. Diagnosis by microscopic examination revealed changes characteristic of delayed radiation necrosis."} {"id": "PMID:1271095", "title": "Sarcoidosis of the spinal cord. Case report.", "content": "A case of intramedullary sarcoidosis simulating a tumor of the cervical spinal cord is presented. Autopsy showed that the disease was limited to the cervical cord and hilar lymph nodes. The literature is reviewed and six cases of histologically documented spinal cord sarcoidosis are discussed.", "contents": "Sarcoidosis of the spinal cord. Case report. A case of intramedullary sarcoidosis simulating a tumor of the cervical spinal cord is presented. Autopsy showed that the disease was limited to the cervical cord and hilar lymph nodes. The literature is reviewed and six cases of histologically documented spinal cord sarcoidosis are discussed."} {"id": "PMID:1271096", "title": "Rapid arteriovenous shunting in a spinal cord ependymoma. Case report.", "content": "A case of ependymoma of the conus medullaris and cauda equina is described in which spinal angiography demonstrated rapid arteriovenous shunting, an angiographic sign which is typical of arteriovenous malformations and which has not been previously reported to occur with ependymomas.", "contents": "Rapid arteriovenous shunting in a spinal cord ependymoma. Case report. A case of ependymoma of the conus medullaris and cauda equina is described in which spinal angiography demonstrated rapid arteriovenous shunting, an angiographic sign which is typical of arteriovenous malformations and which has not been previously reported to occur with ependymomas."} {"id": "PMID:1271097", "title": "Osteoclastoma of the thoracic spine. Case report.", "content": "A case of osteoclastoma arising in the body of the T-9 vertebra is presented. Osteoclastoma rarely involves the vertebrae, and treatment, whether by surgery or radiotherapy, seldom results in eradication of the lesion or prevention of recurrence.", "contents": "Osteoclastoma of the thoracic spine. Case report. A case of osteoclastoma arising in the body of the T-9 vertebra is presented. Osteoclastoma rarely involves the vertebrae, and treatment, whether by surgery or radiotherapy, seldom results in eradication of the lesion or prevention of recurrence."} {"id": "PMID:1271098", "title": "Embolization of a traumatic arteriovenous fistula of the scalp with radiopaque Gelfoam pledgets. Case report and technical note.", "content": "A large traumatic arteriovenous malformation of the scalp was embolized with Pantopaque-saturated Gelfoam pledgets, which made fluoroscopic monitoring of the radiopaque emboli possible. Postembolization angiography demonstrated complete occlusion of the malformation. There is still no clinical or physical evidence of recurrence after an 8-month follow-up period.", "contents": "Embolization of a traumatic arteriovenous fistula of the scalp with radiopaque Gelfoam pledgets. Case report and technical note. A large traumatic arteriovenous malformation of the scalp was embolized with Pantopaque-saturated Gelfoam pledgets, which made fluoroscopic monitoring of the radiopaque emboli possible. Postembolization angiography demonstrated complete occlusion of the malformation. There is still no clinical or physical evidence of recurrence after an 8-month follow-up period."} {"id": "PMID:1271099", "title": "Microblock for occlusion of small vessels. Technical note.", "content": "A small microvascular occluder termed a \"microblock\" is described. It has the advantages of controlled gentle occlusion and small size.", "contents": "Microblock for occlusion of small vessels. Technical note. A small microvascular occluder termed a \"microblock\" is described. It has the advantages of controlled gentle occlusion and small size."} {"id": "PMID:1271100", "title": "Brain-cutting device for correlation of brain scan and autopsy sections. Technical note.", "content": "The authors describe a frame with guides to facilitate accurate correlation of the planes of brain-specimen sections with computerized axial tomography brain scans.", "contents": "Brain-cutting device for correlation of brain scan and autopsy sections. Technical note. The authors describe a frame with guides to facilitate accurate correlation of the planes of brain-specimen sections with computerized axial tomography brain scans."} {"id": "PMID:1271104", "title": "Thallium-201 for myocardial imaging: appearance of the normal heart.", "content": "Thallium-201 myocardial perfusion images were obtained from 13 healthy adults after tracer administration both at rest and at maximal stress. On the rest-injected scan, tracer was seen in left ventricular myocardium, liver, and spleen. In two subjects with resting tachycardia, the right ventricular myocardium was slightly visualized after tracer injection at rest. When tracer was administered at stress, the left ventricular activity was more nearly homogeneous and the left ventricle was better defined on the scan. The left-ventricle-to-lung-background activity ratio increased from 2.4 at rest to 3.4 at stress. The right ventricular myocardium was seen on the stress-injected scan. Phantom studies, performed to define the optimum position for visualization of lesions, showed that small lesions were best defined when seen either en face or in tangent. Scans should be performed at stress whenever possible and multiple views are essential.", "contents": "Thallium-201 for myocardial imaging: appearance of the normal heart. Thallium-201 myocardial perfusion images were obtained from 13 healthy adults after tracer administration both at rest and at maximal stress. On the rest-injected scan, tracer was seen in left ventricular myocardium, liver, and spleen. In two subjects with resting tachycardia, the right ventricular myocardium was slightly visualized after tracer injection at rest. When tracer was administered at stress, the left ventricular activity was more nearly homogeneous and the left ventricle was better defined on the scan. The left-ventricle-to-lung-background activity ratio increased from 2.4 at rest to 3.4 at stress. The right ventricular myocardium was seen on the stress-injected scan. Phantom studies, performed to define the optimum position for visualization of lesions, showed that small lesions were best defined when seen either en face or in tangent. Scans should be performed at stress whenever possible and multiple views are essential."} {"id": "PMID:1271105", "title": "Radionuclide venography: significance of delayed washout; visualization of the saphenous system.", "content": "Venograms were obtained on dogs in which venous thrombosis had been surgically induced. Radionuclide venograms, obtained after injection of 99mTc-labeled microspheres or macroaggregated albumin, showed decreased radioactivity over the areas of venous thrombosis and increased radioactivity over areas of venous stasis. Scintigrams of veins excised after an injection of labeled particles did not delineate thrombi, areas of crush-injured vein, or the venous valves. Delay in the washout of radioactivity on a venogram indicates stasis due to impeded venous flow in the area of thrombosis. A modified technique was developed to obtain simultaneous images of the superficial and deep veins of the leg. Visualization of the superficial veins not only permits detection of superficial abnormalities, but also assists interpretation of the venographic observations of the deep veins.", "contents": "Radionuclide venography: significance of delayed washout; visualization of the saphenous system. Venograms were obtained on dogs in which venous thrombosis had been surgically induced. Radionuclide venograms, obtained after injection of 99mTc-labeled microspheres or macroaggregated albumin, showed decreased radioactivity over the areas of venous thrombosis and increased radioactivity over areas of venous stasis. Scintigrams of veins excised after an injection of labeled particles did not delineate thrombi, areas of crush-injured vein, or the venous valves. Delay in the washout of radioactivity on a venogram indicates stasis due to impeded venous flow in the area of thrombosis. A modified technique was developed to obtain simultaneous images of the superficial and deep veins of the leg. Visualization of the superficial veins not only permits detection of superficial abnormalities, but also assists interpretation of the venographic observations of the deep veins."} {"id": "PMID:1271106", "title": "Compartmental models of cerebral blood flow. Analysis using the 81-keV and 31-keV photons of 133Xe.", "content": "The clearance of 133Xe from the cerebrum after intra-arterial injection was studied in the pig. A mathematical model, consisting of two exponential terms and a constant, was fitted to decay curves obtained for both the 81-keV and the 31-keV radiation of 133Xe. The corresponding exponential terms for the 31-keV and 81-keV curves were found to differ significantly, implying that the two-compartmental model, based on the paritition of the white and gray matter of the brain, is not adequate to describe the clearance process. Other studies have shown that cerebral blood flow is more heterogeneous than the two-compartment model suggests. The discrepancies found here are interpreted as due to the simplification of representing a multiexponential clearance process by means of a two-exponential model.", "contents": "Compartmental models of cerebral blood flow. Analysis using the 81-keV and 31-keV photons of 133Xe. The clearance of 133Xe from the cerebrum after intra-arterial injection was studied in the pig. A mathematical model, consisting of two exponential terms and a constant, was fitted to decay curves obtained for both the 81-keV and the 31-keV radiation of 133Xe. The corresponding exponential terms for the 31-keV and 81-keV curves were found to differ significantly, implying that the two-compartmental model, based on the paritition of the white and gray matter of the brain, is not adequate to describe the clearance process. Other studies have shown that cerebral blood flow is more heterogeneous than the two-compartment model suggests. The discrepancies found here are interpreted as due to the simplification of representing a multiexponential clearance process by means of a two-exponential model."} {"id": "PMID:1271107", "title": "A diagnostic strategy using ventilation-perfusion studies in patients suspect for pulmonary embolism.", "content": "A diagnostic strategy for the assessment of pulmonary embolism was developed using results of scintigraphic examinations in over 100 patients, all of whom had angiographic assessment of their pulmonary vasculature and nearly 50% of whom had combined ventilation-perfusion studies. The highest-probability estimate of pulmonary embolism that could be made in the absence of a ventilation study was 80%. When a ventilation study was added, this probability increased to nearly 100% for patients with multiple large perfusion defects and normal ventilation. For smaller defects with normal ventilation, the probability of pulmonary embolism was only 50%. For perfusion defects corresponding to known radiographic abnormalities, the probability of pulmonary embolism was 25%.", "contents": "A diagnostic strategy using ventilation-perfusion studies in patients suspect for pulmonary embolism. A diagnostic strategy for the assessment of pulmonary embolism was developed using results of scintigraphic examinations in over 100 patients, all of whom had angiographic assessment of their pulmonary vasculature and nearly 50% of whom had combined ventilation-perfusion studies. The highest-probability estimate of pulmonary embolism that could be made in the absence of a ventilation study was 80%. When a ventilation study was added, this probability increased to nearly 100% for patients with multiple large perfusion defects and normal ventilation. For smaller defects with normal ventilation, the probability of pulmonary embolism was only 50%. For perfusion defects corresponding to known radiographic abnormalities, the probability of pulmonary embolism was 25%."} {"id": "PMID:1271108", "title": "Childhood pelvic osteomyelitis presenting as a \"cold\" lesion on bone scan: case report.", "content": "A case of occult pelvic osteomyelitis is presented. The involved portions of the left pubis and left ischium presented as \"cold\" areas on the original bone scan with 99mTc-diphosphonate. The presumed mechanism for this unusual finding in osteomyelitis is compression of the microcirculation to bone by subperiosteal and intraosseous pus.", "contents": "Childhood pelvic osteomyelitis presenting as a \"cold\" lesion on bone scan: case report. A case of occult pelvic osteomyelitis is presented. The involved portions of the left pubis and left ischium presented as \"cold\" areas on the original bone scan with 99mTc-diphosphonate. The presumed mechanism for this unusual finding in osteomyelitis is compression of the microcirculation to bone by subperiosteal and intraosseous pus."} {"id": "PMID:1271109", "title": "Radionuclide angiocardiographic calculation of the ratio of left-to-right heart outputs in a patient with unusual cardiovascular anatomy: case report.", "content": "The subject of this case report is an unusual patient whose right lung receives blood from the right heart and whose left lung receives blood from the left heart. Due to this unusual anatomy, it was possible to calculate the ratio of the outputs of the left and right hearts using standard techniques.", "contents": "Radionuclide angiocardiographic calculation of the ratio of left-to-right heart outputs in a patient with unusual cardiovascular anatomy: case report. The subject of this case report is an unusual patient whose right lung receives blood from the right heart and whose left lung receives blood from the left heart. Due to this unusual anatomy, it was possible to calculate the ratio of the outputs of the left and right hearts using standard techniques."} {"id": "PMID:1271110", "title": "Focally increased activity on scinticisternography: report of two cases.", "content": "Two cases where focally increased activity was noted on scinticisternography are reported. One case involves a documented arteriovenous malformation, and the other, documented embolic vascular disease. After a review of the pertient literature, various other pathologic entities associated with similar scan findings are described. Possible causative mechanisms are discussed.", "contents": "Focally increased activity on scinticisternography: report of two cases. Two cases where focally increased activity was noted on scinticisternography are reported. One case involves a documented arteriovenous malformation, and the other, documented embolic vascular disease. After a review of the pertient literature, various other pathologic entities associated with similar scan findings are described. Possible causative mechanisms are discussed."} {"id": "PMID:1271111", "title": "Development of new radiopharmaceuticals based on N-substitution of iminodiacetic acid.", "content": "A new approach to radiopharmaceutical design is demonstrated, in which small chelating groups capable of binding gamma-emitting radiometals are attached to biologically active molecules, thus producing radiopharmaceuticals based on bifunctional drug and biochemical analogs. The chelating group iminodiacetic acid has been evaluated for this role by examining two N-substituted iminodiacetic acids: methyliminodiacetic acid (MIDA) and N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid (HIDA). Radiochemical and biologic studies showed that both agents were obtained in high radiochemical purity, were stable in vitro and in vivo, and possessed biologic distributions governed almost exclusively by the N-substituted group. These characteristics of 99mTc-labeled N-substituted iminodiacetic acids, prepared using an \"instant kit\" method, provide the basis for a valuable new class of radiopharmaceuticals based on bifunctional drug and biochemical analogs.", "contents": "Development of new radiopharmaceuticals based on N-substitution of iminodiacetic acid. A new approach to radiopharmaceutical design is demonstrated, in which small chelating groups capable of binding gamma-emitting radiometals are attached to biologically active molecules, thus producing radiopharmaceuticals based on bifunctional drug and biochemical analogs. The chelating group iminodiacetic acid has been evaluated for this role by examining two N-substituted iminodiacetic acids: methyliminodiacetic acid (MIDA) and N-(2,6-dimethylphenylcarbamoylmethyl)iminodiacetic acid (HIDA). Radiochemical and biologic studies showed that both agents were obtained in high radiochemical purity, were stable in vitro and in vivo, and possessed biologic distributions governed almost exclusively by the N-substituted group. These characteristics of 99mTc-labeled N-substituted iminodiacetic acids, prepared using an \"instant kit\" method, provide the basis for a valuable new class of radiopharmaceuticals based on bifunctional drug and biochemical analogs."} {"id": "PMID:1271112", "title": "Field flood uniformity correction: benefits or pitfalls?", "content": "Strict quality control of scintillation camera images is increasingly recognized as important in a nuclear medicine laboratory. The field flood uniformity of the camera should be tested daily. A variety of commercially available data systems facilitate the above task. Concomitantly, scintigrams are increasingly being corrected for uniformity, namely, unbalanced photo-multiplier tubes, uniformity correction can occasionally, depending on the scatter fraction, produce clinically significant artifacts. This effect is due to the application of a linear correction factor to a nonlinear phenomenon.", "contents": "Field flood uniformity correction: benefits or pitfalls? Strict quality control of scintillation camera images is increasingly recognized as important in a nuclear medicine laboratory. The field flood uniformity of the camera should be tested daily. A variety of commercially available data systems facilitate the above task. Concomitantly, scintigrams are increasingly being corrected for uniformity, namely, unbalanced photo-multiplier tubes, uniformity correction can occasionally, depending on the scatter fraction, produce clinically significant artifacts. This effect is due to the application of a linear correction factor to a nonlinear phenomenon."} {"id": "PMID:1271113", "title": "Stability of radiothyroxine plasma disappearance curve despite catharsis and unblocked thyroidal uptake of radioiodide.", "content": "Plasma radioactivity was measured over 21 days after an intravenous injection of 50 muCi of 125I-T4 in eight normal men. No thyroid-blocking medication was given. Four subjects (castor oil group) received 30 ml of castor oil on each of Days 13, 14, and 15, while the other four subjects (control group) were studied without medication. After A 5-day equilibration period, plasma 125I-T4 was measured on Days 5-13 in order to calculate the disappearance curve for each subject and to derive the mean for each experimental group. The curves were then extrapolated to Day 21. Measured radioactivity did not depart significantly from the extrapolated line, either during the castor oil period (Days 14, 15, and 16) or during the recovery period (Days 17, 19, and 21). The castor oil, therefore, had no observable effect on the clearance of plasma radioactivity. None of the subjects had a late increase in plasma radioactivity to suggest recirculation of radioiodide or buildup of iodoproteins. In normal subjects, radiothyroxine plasma levels up to 21 days are not significantly affected by short-term catharsis or by failure to block thyroidal radioiodide uptake.", "contents": "Stability of radiothyroxine plasma disappearance curve despite catharsis and unblocked thyroidal uptake of radioiodide. Plasma radioactivity was measured over 21 days after an intravenous injection of 50 muCi of 125I-T4 in eight normal men. No thyroid-blocking medication was given. Four subjects (castor oil group) received 30 ml of castor oil on each of Days 13, 14, and 15, while the other four subjects (control group) were studied without medication. After A 5-day equilibration period, plasma 125I-T4 was measured on Days 5-13 in order to calculate the disappearance curve for each subject and to derive the mean for each experimental group. The curves were then extrapolated to Day 21. Measured radioactivity did not depart significantly from the extrapolated line, either during the castor oil period (Days 14, 15, and 16) or during the recovery period (Days 17, 19, and 21). The castor oil, therefore, had no observable effect on the clearance of plasma radioactivity. None of the subjects had a late increase in plasma radioactivity to suggest recirculation of radioiodide or buildup of iodoproteins. In normal subjects, radiothyroxine plasma levels up to 21 days are not significantly affected by short-term catharsis or by failure to block thyroidal radioiodide uptake."} {"id": "PMID:1271116", "title": "Significance of choline synthesis in the oxidation of the methionine methyl group in rats.", "content": "Experiments were conducted to assess the significance of de novo choline synthesis in the oxidative metabolism of the methyl group of L-methionine in the rat. Comparison of the rates of 14CO2 production by rats fed diets containing equimolar or equal methyl loads of [methyl-14C]methionine, [methyl-14C] choline, [methyl-14C] betaine and [methyl-14C] sarcosine revealed that the methyl groups of choline, betaine and sarcosine were oxidized at rates nearly equivalent to or exceeding that of the methionine methyl group. However, the results of a second series of in vivo experiments using non-radioactive choline or betaine as intermediary trapping pools indicated that little newly formed radioactive choline was released from tissue phospholipid choline during the period of rapid 14CO2 production from [14CH3] methionine. Incorporation of the methionine methyl group into phospholipid choline by incubated liver slices was strongly inhibited by 2-methoxyethanol without a parallel inhibition of methionine methyl group oxidation. Results of these in vitro studies also indicated that the metabolic pathway responsible for the transfer of the methionine methyl group into choline and that responsible for its oxidation to CO2 differ widely in the ease with which they can be saturated by L-methionine. It is concluded that essentially all of the methionine methyl group oxidation in vitro and that occurring during the absorptive period in vivo must depend primarily on pathways other than those leading to the synthesis of choline.", "contents": "Significance of choline synthesis in the oxidation of the methionine methyl group in rats. Experiments were conducted to assess the significance of de novo choline synthesis in the oxidative metabolism of the methyl group of L-methionine in the rat. Comparison of the rates of 14CO2 production by rats fed diets containing equimolar or equal methyl loads of [methyl-14C]methionine, [methyl-14C] choline, [methyl-14C] betaine and [methyl-14C] sarcosine revealed that the methyl groups of choline, betaine and sarcosine were oxidized at rates nearly equivalent to or exceeding that of the methionine methyl group. However, the results of a second series of in vivo experiments using non-radioactive choline or betaine as intermediary trapping pools indicated that little newly formed radioactive choline was released from tissue phospholipid choline during the period of rapid 14CO2 production from [14CH3] methionine. Incorporation of the methionine methyl group into phospholipid choline by incubated liver slices was strongly inhibited by 2-methoxyethanol without a parallel inhibition of methionine methyl group oxidation. Results of these in vitro studies also indicated that the metabolic pathway responsible for the transfer of the methionine methyl group into choline and that responsible for its oxidation to CO2 differ widely in the ease with which they can be saturated by L-methionine. It is concluded that essentially all of the methionine methyl group oxidation in vitro and that occurring during the absorptive period in vivo must depend primarily on pathways other than those leading to the synthesis of choline."} {"id": "PMID:1271117", "title": "The effect of a nonabsorbable lipid, sucrose polyester, on the absorption of dietary cholesterol by the rat.", "content": "The absorption of cholesterol from diets containing various proportions of triglycerides and an unabsorbable fat, sucrose polyester (SPE), was determined in rats. Each replacement of 1% dietary triglyceride with SPE resulted in a 1.2% decrease in cholesterol absorption. The SPE was a mixture of the hexa-, hepta- and octa-esters of long chain fatty acids. The physical properties of this material are similar to those of the usual dietary triglycerides. Relative to these studies, cholesterol was found to be equally soluble in triolein or SPE. If water was present as well, the solubility of the sterol was decreased by the same amount in both fats. The distribution coefficients of cholesterol between an oil phase of either triolein or SPE and a micellar phase simulating that found in the lumen of the intestinal tract were identical. These two types of fats differ in that SPE is neither digested nor absorbed. The decrease in cholesterol absorption is attributed to the continued presence of an oil phase of SPE in the lumen of the intestine. Dietary cholesterol distributes itself between this oil phase and the micellar phase. That portion in the oil phase is not absorbed but is egested in the feces.", "contents": "The effect of a nonabsorbable lipid, sucrose polyester, on the absorption of dietary cholesterol by the rat. The absorption of cholesterol from diets containing various proportions of triglycerides and an unabsorbable fat, sucrose polyester (SPE), was determined in rats. Each replacement of 1% dietary triglyceride with SPE resulted in a 1.2% decrease in cholesterol absorption. The SPE was a mixture of the hexa-, hepta- and octa-esters of long chain fatty acids. The physical properties of this material are similar to those of the usual dietary triglycerides. Relative to these studies, cholesterol was found to be equally soluble in triolein or SPE. If water was present as well, the solubility of the sterol was decreased by the same amount in both fats. The distribution coefficients of cholesterol between an oil phase of either triolein or SPE and a micellar phase simulating that found in the lumen of the intestinal tract were identical. These two types of fats differ in that SPE is neither digested nor absorbed. The decrease in cholesterol absorption is attributed to the continued presence of an oil phase of SPE in the lumen of the intestine. Dietary cholesterol distributes itself between this oil phase and the micellar phase. That portion in the oil phase is not absorbed but is egested in the feces."} {"id": "PMID:1271118", "title": "Isolation of monoferric phytate from wheat bran and its biological value as an iron source to the rat.", "content": "The objectives of the study were to isolate and chemically characterize the iron in wheat and to determine the biological availability to the rat of the iron as the purified complex(es). Hard wheat bran contained no butanol extractable or water extractable iron, but approximately 60% of the iron was extracted by 1 to 1.2 M NaCl or ammonium acetate solution. This salt extractable iron complex was purified and identified as monoferric phytate. The purified monoferric phytate was soluble in water. Synthetic monoferric phytate was prepared from sodium phytate and ferric chloride and determined to have spectral characteristics and gel filtration chromatography behavior identical to the complex isolated from wheat bran. The butanol-water-salt extracted bran residue contained no detectable phytate and an as yet uncharacterized form of iron. The biological availability of the iron to the rat was determined by a hemoglobin depletion-repletion bioassay. The relative biological value of the iron as monoferric phytate, either isolated from wheat bran or the synthetic product, was equal to the reference compound, ferrous ammonium sulfate. In contrast, the biological availability of the iron in the bran residue was significantly lower and the low biological availability of an insoluble form of ferric phytate was confirmed. It is concluded that the major portion of the iron in wheat is monoferric phytate and has a high biological availability to the rat. Monoferric phytate in bran may be bound to cationic sites of proteins or other cellular components and utilization of the iron may be through solubilization of the monoferric phytate by ion exchange type mechanism rather than by hydrolysis of the phytate as has been postulated.", "contents": "Isolation of monoferric phytate from wheat bran and its biological value as an iron source to the rat. The objectives of the study were to isolate and chemically characterize the iron in wheat and to determine the biological availability to the rat of the iron as the purified complex(es). Hard wheat bran contained no butanol extractable or water extractable iron, but approximately 60% of the iron was extracted by 1 to 1.2 M NaCl or ammonium acetate solution. This salt extractable iron complex was purified and identified as monoferric phytate. The purified monoferric phytate was soluble in water. Synthetic monoferric phytate was prepared from sodium phytate and ferric chloride and determined to have spectral characteristics and gel filtration chromatography behavior identical to the complex isolated from wheat bran. The butanol-water-salt extracted bran residue contained no detectable phytate and an as yet uncharacterized form of iron. The biological availability of the iron to the rat was determined by a hemoglobin depletion-repletion bioassay. The relative biological value of the iron as monoferric phytate, either isolated from wheat bran or the synthetic product, was equal to the reference compound, ferrous ammonium sulfate. In contrast, the biological availability of the iron in the bran residue was significantly lower and the low biological availability of an insoluble form of ferric phytate was confirmed. It is concluded that the major portion of the iron in wheat is monoferric phytate and has a high biological availability to the rat. Monoferric phytate in bran may be bound to cationic sites of proteins or other cellular components and utilization of the iron may be through solubilization of the monoferric phytate by ion exchange type mechanism rather than by hydrolysis of the phytate as has been postulated."} {"id": "PMID:1271119", "title": "Prenatal aspects of ascorbic acid metabolism in the albino rat.", "content": "Transfer of ascorbic acid and/or its derivatives from maternal blood into the fetus was studied during the last week of gestation in the rat. Rats were injected intravenously with [1-14C]-ascorbic acid and the rate of transfer estimated by the concentration and content of label present in placentas and fetuses. At all times studied the concentration of label in the placenta was greater than in the fetus. The highest capacity of the placenta to concentrate label was found on day 15 decreasing to a low at day 19 and again increasing up to day 21. While in the fetuses, the concentration of label per gram of tissue remained remarkably constant throughout the study. The quantity of labeled compounds transferred into the fetus per gram of placental tissue increased between day 15 and day 21 of gestation.", "contents": "Prenatal aspects of ascorbic acid metabolism in the albino rat. Transfer of ascorbic acid and/or its derivatives from maternal blood into the fetus was studied during the last week of gestation in the rat. Rats were injected intravenously with [1-14C]-ascorbic acid and the rate of transfer estimated by the concentration and content of label present in placentas and fetuses. At all times studied the concentration of label in the placenta was greater than in the fetus. The highest capacity of the placenta to concentrate label was found on day 15 decreasing to a low at day 19 and again increasing up to day 21. While in the fetuses, the concentration of label per gram of tissue remained remarkably constant throughout the study. The quantity of labeled compounds transferred into the fetus per gram of placental tissue increased between day 15 and day 21 of gestation."} {"id": "PMID:1271120", "title": "Effect of fluoride on the mobilization of skeletal magnesium and soft-tissue calcinosis during acute magnesium deficiency in the rat.", "content": "To investigate the effect of fluoride on the mobilization of skeletal magnesium and on kidney calcification during magnesium depletion, male Holtzman rats were fed a magnesium-sufficient diet (400 ppm of magnesium) and drinking water containing either 0, 50 or 100 ppm of fluoride for a 20-day period prior to the initiation of magnesium deficiency. The high fluoride regimen resulted in a 100-fold increase in the fluoride content of the skeleton. On day 20 magnesium depletion was initiated by feeding the animals a diet containing 12 ppm of magnesium. Over a 4-week period of magnesium deprivation, a 26% decrease of the total magnesium in the humeri was observed. Fluoride exerted a significant effect in retarding the mobilization of skeletal magnesium. Four weeks of magnesium deficiency was associated with a decreased rate of skeletal mineral accretion and with an increase in the kidney calcium content. The decreased rate of mineral accretion was accentuated by the administration of fluoride during the deficiency state. While fluoride exerted an initial protective effect on calcinosis of the kidneys, the overall effect of the administration of fluoride during magnesium deficiency was to promote calcification of the kidneys rather than to prevent it.", "contents": "Effect of fluoride on the mobilization of skeletal magnesium and soft-tissue calcinosis during acute magnesium deficiency in the rat. To investigate the effect of fluoride on the mobilization of skeletal magnesium and on kidney calcification during magnesium depletion, male Holtzman rats were fed a magnesium-sufficient diet (400 ppm of magnesium) and drinking water containing either 0, 50 or 100 ppm of fluoride for a 20-day period prior to the initiation of magnesium deficiency. The high fluoride regimen resulted in a 100-fold increase in the fluoride content of the skeleton. On day 20 magnesium depletion was initiated by feeding the animals a diet containing 12 ppm of magnesium. Over a 4-week period of magnesium deprivation, a 26% decrease of the total magnesium in the humeri was observed. Fluoride exerted a significant effect in retarding the mobilization of skeletal magnesium. Four weeks of magnesium deficiency was associated with a decreased rate of skeletal mineral accretion and with an increase in the kidney calcium content. The decreased rate of mineral accretion was accentuated by the administration of fluoride during the deficiency state. While fluoride exerted an initial protective effect on calcinosis of the kidneys, the overall effect of the administration of fluoride during magnesium deficiency was to promote calcification of the kidneys rather than to prevent it."} {"id": "PMID:1271121", "title": "Influence of dietary selenium on lead toxicity in the rat.", "content": "An investigation of the influence of dietary selenium (0.015, 0.05, 0.50, 1.0 ppm) on toxicity of dietary lead (0 and 200 ppm) in the young male rat indicated that selenium was mildly protective against the toxic effects of lead, but only up to 0.50 ppm selenium. At the excess selenium dietary level an exaggeration of lead toxicity was observed. Criteria employed to judge the effects of dietary selenium on lead toxicity included tissue lead concentration and urinary delta-aminolevulinic acid excretion. One exception to the exaggeration effect of excess selenium on lead toxicity was the protective effect of selenium on liver delta-aminolevulinic acid dehydratase activity. Since lead depressed kidney selenium concentration, lead may act as an antagonist to selenium metabolism.", "contents": "Influence of dietary selenium on lead toxicity in the rat. An investigation of the influence of dietary selenium (0.015, 0.05, 0.50, 1.0 ppm) on toxicity of dietary lead (0 and 200 ppm) in the young male rat indicated that selenium was mildly protective against the toxic effects of lead, but only up to 0.50 ppm selenium. At the excess selenium dietary level an exaggeration of lead toxicity was observed. Criteria employed to judge the effects of dietary selenium on lead toxicity included tissue lead concentration and urinary delta-aminolevulinic acid excretion. One exception to the exaggeration effect of excess selenium on lead toxicity was the protective effect of selenium on liver delta-aminolevulinic acid dehydratase activity. Since lead depressed kidney selenium concentration, lead may act as an antagonist to selenium metabolism."} {"id": "PMID:1271122", "title": "Protein quality of some representative Latin American diets by rat bioassay.", "content": "A study of the protein quality of twelve different food-mixtures common to Latin America, was performed by rat bioassay. The individual foods were cooked and dried and then mixed in the appropriate proportions resembling the original meals. Rats of the Sprague-Dawley strain were used for the bioassays. Special emphasis was given to the methodology of the slope-ratio techniques preconized by Hegsted and his associates who have claimed that classical bioassays overestimate the nutritive value of poor quality proteins. RNV and RPV values were calculated using the slope-ratio technique, with and without use of a non protein control group. PER, NPR, relative NPR and utilizable protein were also calculated using the same data. The amino acid composition was determined and the score against the FAO/WHO 1973 pattern was compared with the bioassays. Protein value of the diets was also calculated from food table data. Agreement was good between all the procedures especially for the calculation of utilizable protein although the poorest diet containing little else but maize was somewhat overestimated in its quality by calculation from food table data. Thus, in general, estimates for protein quality of diets by standard bioassay techniques and even by amino acid scoring procedures gave values comparable to those obtained by the slope-ratio assays. The large scale re-evaluation suggested for all protein quality data prior to the slope-ratio techniques may not in fact be necessary.", "contents": "Protein quality of some representative Latin American diets by rat bioassay. A study of the protein quality of twelve different food-mixtures common to Latin America, was performed by rat bioassay. The individual foods were cooked and dried and then mixed in the appropriate proportions resembling the original meals. Rats of the Sprague-Dawley strain were used for the bioassays. Special emphasis was given to the methodology of the slope-ratio techniques preconized by Hegsted and his associates who have claimed that classical bioassays overestimate the nutritive value of poor quality proteins. RNV and RPV values were calculated using the slope-ratio technique, with and without use of a non protein control group. PER, NPR, relative NPR and utilizable protein were also calculated using the same data. The amino acid composition was determined and the score against the FAO/WHO 1973 pattern was compared with the bioassays. Protein value of the diets was also calculated from food table data. Agreement was good between all the procedures especially for the calculation of utilizable protein although the poorest diet containing little else but maize was somewhat overestimated in its quality by calculation from food table data. Thus, in general, estimates for protein quality of diets by standard bioassay techniques and even by amino acid scoring procedures gave values comparable to those obtained by the slope-ratio assays. The large scale re-evaluation suggested for all protein quality data prior to the slope-ratio techniques may not in fact be necessary."} {"id": "PMID:1271133", "title": "The influence of enrichment with cholesterol on the phagocytic activity of rat macrophages.", "content": "Prolonged treatment of rats with a cholesterol-rich diet induced hypercholesterolaemia and increased free cholesterol content of peritoneal macrophages. A 2-2 times increase in plasma membrane cholesterol was demonstrated in cholesterol-enriched macrophages. These cells showed a significant inhibition of phagocytosis. The inhibition was 37-0% and 81-7% for latex particles or lipid droplets, respectively.", "contents": "The influence of enrichment with cholesterol on the phagocytic activity of rat macrophages. Prolonged treatment of rats with a cholesterol-rich diet induced hypercholesterolaemia and increased free cholesterol content of peritoneal macrophages. A 2-2 times increase in plasma membrane cholesterol was demonstrated in cholesterol-enriched macrophages. These cells showed a significant inhibition of phagocytosis. The inhibition was 37-0% and 81-7% for latex particles or lipid droplets, respectively."} {"id": "PMID:1271134", "title": "The lymphoreticular response to a transplanted adenovirus 12-induced tumour of CBA mice.", "content": "The growth and structure of a virus-induced tumour has been studied in normal and immunised animals. Retardation of tumour growth in immunised animals is accompanied by a lymphoreticular infiltrate; macrophages ingest apparently intact tumour cells.", "contents": "The lymphoreticular response to a transplanted adenovirus 12-induced tumour of CBA mice. The growth and structure of a virus-induced tumour has been studied in normal and immunised animals. Retardation of tumour growth in immunised animals is accompanied by a lymphoreticular infiltrate; macrophages ingest apparently intact tumour cells."} {"id": "PMID:1271135", "title": "The effect of hyperthermia on the neuroepithelium of the 21-day guinea-pig foetus: histologic and ultrastructural study.", "content": "Hyperthermia was induced in guinea-pigs on day 21 of gestation by placing them in an incubator set at 42-5 degrees-43-0 degrees C for 1 hr. At intervals thereafter foetuses were removed from the uterus and sections of the telencephalon were prepared for light and electron microscopy. The histologic and ultrastructural appearance of the telencephalon of the normal 21-day guinea-pig foetus was described for comparative purposes. Damage to cells in mitosis characterised by clumping of chromosomes, and dispersal of polysomes in interphase cells were observed immediately after hyperthermia. Breakdown of the network of junctional complexes was apparent at 4 hr and cellular proliferation was inhibited for 6-8 hr. Degenerative changes and cell deaths were observed deep in the venticular zone after 8 hr; the extent of cell death was related to the post-stressing temperature. Proliferation was resumed at 8 hr and damaged and dead cells moved outward toward the intermediate zone. Phagocytosis of debris by large mononuclear cells was a common finding. Cytoplasmic inclusions, some of which were Feulgen-positive, were present in otherwise normal ventricular cells. Occasional dead cells and empty spaces were present in the ventricular zone at 24 hr and by 48 hr the ventricular zone was normal in appearance. It was concluded that previously observed micrencephaly in the offspring of guine-pig mothers which were heat stressed on day 21 of gestation resulted from a temporary cessation of proliferation and partial depopulation of the proliferating neuroepithelium.", "contents": "The effect of hyperthermia on the neuroepithelium of the 21-day guinea-pig foetus: histologic and ultrastructural study. Hyperthermia was induced in guinea-pigs on day 21 of gestation by placing them in an incubator set at 42-5 degrees-43-0 degrees C for 1 hr. At intervals thereafter foetuses were removed from the uterus and sections of the telencephalon were prepared for light and electron microscopy. The histologic and ultrastructural appearance of the telencephalon of the normal 21-day guinea-pig foetus was described for comparative purposes. Damage to cells in mitosis characterised by clumping of chromosomes, and dispersal of polysomes in interphase cells were observed immediately after hyperthermia. Breakdown of the network of junctional complexes was apparent at 4 hr and cellular proliferation was inhibited for 6-8 hr. Degenerative changes and cell deaths were observed deep in the venticular zone after 8 hr; the extent of cell death was related to the post-stressing temperature. Proliferation was resumed at 8 hr and damaged and dead cells moved outward toward the intermediate zone. Phagocytosis of debris by large mononuclear cells was a common finding. Cytoplasmic inclusions, some of which were Feulgen-positive, were present in otherwise normal ventricular cells. Occasional dead cells and empty spaces were present in the ventricular zone at 24 hr and by 48 hr the ventricular zone was normal in appearance. It was concluded that previously observed micrencephaly in the offspring of guine-pig mothers which were heat stressed on day 21 of gestation resulted from a temporary cessation of proliferation and partial depopulation of the proliferating neuroepithelium."} {"id": "PMID:1271136", "title": "Histological effects of ductal ligation of salivary glands of the cat.", "content": "Forty-two submandibular, 32 sublingual and 31 parotid glands have been examined microscopically after ductal ligation avoiding the nerves for periods from 1 day to 1 yr. After an initial increase in size, there was over-all atrophy in all three glands. In the parotid gland the response was uniform and there was progressive atrophy until most of the acini were extremely atrophic. However, in the submandibular and sublingual glands the response was very variable, and although in some glands most of the acini were extremely atrophic, in other glands there was far less atrophy and most of the remaining acini appeared more or less similar to normal despite prolonged ligation. These results contrast with those of earlier experimental studies on ductal ligation, but have similarities with observations on the behaviour of human salivary glands.", "contents": "Histological effects of ductal ligation of salivary glands of the cat. Forty-two submandibular, 32 sublingual and 31 parotid glands have been examined microscopically after ductal ligation avoiding the nerves for periods from 1 day to 1 yr. After an initial increase in size, there was over-all atrophy in all three glands. In the parotid gland the response was uniform and there was progressive atrophy until most of the acini were extremely atrophic. However, in the submandibular and sublingual glands the response was very variable, and although in some glands most of the acini were extremely atrophic, in other glands there was far less atrophy and most of the remaining acini appeared more or less similar to normal despite prolonged ligation. These results contrast with those of earlier experimental studies on ductal ligation, but have similarities with observations on the behaviour of human salivary glands."} {"id": "PMID:1271137", "title": "The application of a serum 17OH-progesterone radioimmunoassay to the diagnosis and management of congenital adrenal hyperplasia.", "content": "Serum concentrations of 17OH-progesterone were studied serially over 24 hours in 13 treated and untreated patients with the C21 hydroxylase form of congenital adrenal hyperplasia. The results were correlated with measurements of plasma renin activity, serum electrolytes, and urinary 17-ketosteroids and pregnanetriol. In 500 healthy subjects from birth to adult life, serum 17OH-pregesterone levels ranged from 5 to 315 ng/dl. In untreated CAH, serum 17OH-progesterone was markedly elevated (2,000 to 80,000 ng/dl). Treatment with cortisol (20 to 30 mg/m2/day in 3 doses) resulted in normal serum 17OH-progesterone levels in both non-salt-losing and salt-losing patients receiving adequate mineralocorticoid. Even slightly inadequate mineralocorticoid therapy (shown by high plasma renin activity with normal serum electrolytes) was associated with elevated 17OH-progesterone (to 65,000 ng/dl) in spite of usually effective doses of cortisol. Some patients showed isolated 17OH-progesterone elevations (usually early morning), a situation which requires only revision of the cortisol dosage schedule without an increase in total dosage. The data confirm the value of 17OH-progesterone assays in both the diagnosis and management of CAH. Taken together with determinations of plasma renin activity, serum 17OH-progesterone assays can permit more exact control of CAH without excessive doses of glucocorticoid.", "contents": "The application of a serum 17OH-progesterone radioimmunoassay to the diagnosis and management of congenital adrenal hyperplasia. Serum concentrations of 17OH-progesterone were studied serially over 24 hours in 13 treated and untreated patients with the C21 hydroxylase form of congenital adrenal hyperplasia. The results were correlated with measurements of plasma renin activity, serum electrolytes, and urinary 17-ketosteroids and pregnanetriol. In 500 healthy subjects from birth to adult life, serum 17OH-pregesterone levels ranged from 5 to 315 ng/dl. In untreated CAH, serum 17OH-progesterone was markedly elevated (2,000 to 80,000 ng/dl). Treatment with cortisol (20 to 30 mg/m2/day in 3 doses) resulted in normal serum 17OH-progesterone levels in both non-salt-losing and salt-losing patients receiving adequate mineralocorticoid. Even slightly inadequate mineralocorticoid therapy (shown by high plasma renin activity with normal serum electrolytes) was associated with elevated 17OH-progesterone (to 65,000 ng/dl) in spite of usually effective doses of cortisol. Some patients showed isolated 17OH-progesterone elevations (usually early morning), a situation which requires only revision of the cortisol dosage schedule without an increase in total dosage. The data confirm the value of 17OH-progesterone assays in both the diagnosis and management of CAH. Taken together with determinations of plasma renin activity, serum 17OH-progesterone assays can permit more exact control of CAH without excessive doses of glucocorticoid."} {"id": "PMID:1271138", "title": "Hepatic porto-enterostomy or cholecystostomy in the treatment of extrahepatic biliary atresia. A study of 49 cases.", "content": "Hepatic porto-enterostomy or cholecystostomy (Kasai's procedure) was successful in restoring bile flow in 31 of 49 patients with \"noncorrectable\" extrahepatic biliary atresia. However, all but one of the 31 developed acute or chronic complications such as cholangitis, bile peritonitis, or portal hypertension. During a five-year follow-up period, 26 (53%) died while 9 of the 23 survivors continue to manifest chronic or recurrent cholangitis. Thirteen of the 19 survivors who are more than one year of age have developed portal hypertension. These complications limit the prognosis of infants with \"noncorrectable\" biliary malformations.", "contents": "Hepatic porto-enterostomy or cholecystostomy in the treatment of extrahepatic biliary atresia. A study of 49 cases. Hepatic porto-enterostomy or cholecystostomy (Kasai's procedure) was successful in restoring bile flow in 31 of 49 patients with \"noncorrectable\" extrahepatic biliary atresia. However, all but one of the 31 developed acute or chronic complications such as cholangitis, bile peritonitis, or portal hypertension. During a five-year follow-up period, 26 (53%) died while 9 of the 23 survivors continue to manifest chronic or recurrent cholangitis. Thirteen of the 19 survivors who are more than one year of age have developed portal hypertension. These complications limit the prognosis of infants with \"noncorrectable\" biliary malformations."} {"id": "PMID:1271139", "title": "The acute and transient nature of idiopathic immune hemolytic anemia in childhood.", "content": "The records of 22 children with the diagnosis of idiopathic immune hemolytic anemia were reviewed. Fifty per cent of the children had a history of an antecedent infection and 32% had underlying immune deficiency or lymphoproliferative diseases. The majority (77%) of the patients had an acute self-limited disease which was frequently associated with a positive complement or nongamma Coombs test. The anemia was usually severe, and a number of the children had reticulocytopenia at the time of diagnosis. These children responded rapidly to transfusions and corticosteroids and generally remained well on follow-up. Immunosuppressive drugs did not prove useful in two patients refractory to prednisone, but splenectomy was apparently beneficial in three of four patients so treated. Mortality rate was 18%, with most of the deaths related to an underlying disease.", "contents": "The acute and transient nature of idiopathic immune hemolytic anemia in childhood. The records of 22 children with the diagnosis of idiopathic immune hemolytic anemia were reviewed. Fifty per cent of the children had a history of an antecedent infection and 32% had underlying immune deficiency or lymphoproliferative diseases. The majority (77%) of the patients had an acute self-limited disease which was frequently associated with a positive complement or nongamma Coombs test. The anemia was usually severe, and a number of the children had reticulocytopenia at the time of diagnosis. These children responded rapidly to transfusions and corticosteroids and generally remained well on follow-up. Immunosuppressive drugs did not prove useful in two patients refractory to prednisone, but splenectomy was apparently beneficial in three of four patients so treated. Mortality rate was 18%, with most of the deaths related to an underlying disease."} {"id": "PMID:1271140", "title": "Granulopoiesis in childhood aplastic anemia.", "content": "The soft agar technique was employed to investigate factors involved in the regulation of granulopoiesis in ten children with aplastic anemia. Children with AA had greatly reduced numbers of granulocytic colony-forming cells in their bone marrow and in their peripheral blood when compared to \"control\" children. Colony-stimulating activity was decreased in five of the ten children tested. Serum from eight children with AA did not inhibit colony formation when added to normal adult bone marrow cells in culture. The defect in AA residues in the stem cell, with involvement of the CSA-producing cells in some cases. The serum of these patients does not contain an inhibitor of granulopoiesis.", "contents": "Granulopoiesis in childhood aplastic anemia. The soft agar technique was employed to investigate factors involved in the regulation of granulopoiesis in ten children with aplastic anemia. Children with AA had greatly reduced numbers of granulocytic colony-forming cells in their bone marrow and in their peripheral blood when compared to \"control\" children. Colony-stimulating activity was decreased in five of the ten children tested. Serum from eight children with AA did not inhibit colony formation when added to normal adult bone marrow cells in culture. The defect in AA residues in the stem cell, with involvement of the CSA-producing cells in some cases. The serum of these patients does not contain an inhibitor of granulopoiesis."} {"id": "PMID:1271141", "title": "Malabsorption of iron in children with iron deficiency.", "content": "Inability to absorb oral iron is believed to be an extremely rare cause of therapeutic failure in the treatment of iron deficiency anemia. Six patients who had failed to respond to oral iron therapy were studied by a simple oral absorption test and contrasted with 25 patients with untreated iron deficiency anemia and 10 normal subjects. All six of the patients who were therapeutic failures demonstrated impaired iron absorption in the absence of other clinical evidence of gastrointestinal disease. In the 25 newly diagnosed patients with iron deficiency. 24 demonstrated elevated iron absorptions while 10 ironreplete normal subjects had minimal elevations in their serum iron values following the administration of the test dose of 1 mg of elemental iron per kilogram. When the therapeutic failures were treated with parenteral iron, all had a therapeutic response. In addition, after treatment the impaired absorption of iron improved transiently. All children who absorbed iron readily responded to oral iron therapy.", "contents": "Malabsorption of iron in children with iron deficiency. Inability to absorb oral iron is believed to be an extremely rare cause of therapeutic failure in the treatment of iron deficiency anemia. Six patients who had failed to respond to oral iron therapy were studied by a simple oral absorption test and contrasted with 25 patients with untreated iron deficiency anemia and 10 normal subjects. All six of the patients who were therapeutic failures demonstrated impaired iron absorption in the absence of other clinical evidence of gastrointestinal disease. In the 25 newly diagnosed patients with iron deficiency. 24 demonstrated elevated iron absorptions while 10 ironreplete normal subjects had minimal elevations in their serum iron values following the administration of the test dose of 1 mg of elemental iron per kilogram. When the therapeutic failures were treated with parenteral iron, all had a therapeutic response. In addition, after treatment the impaired absorption of iron improved transiently. All children who absorbed iron readily responded to oral iron therapy."} {"id": "PMID:1271142", "title": "Hyponatremia in sickle cell disease. A renal salt-losing state.", "content": "Severe hyponatremia has been observed in three children with sickle cell disease, and mild hyponatremia was noted during 36% of random hospitalizations for sickle crisis secondary to vasoocclusion or infection. Serum and urinary electrolytes were therefore studied in such patients. Hyponatremia was found in 52% of patients hospitalized with pain and/or fever, even though they received large amounts of sodium intravenously. Urine sodium losses were high with frequent negative sodium balance and weight loss. When well, these patients did not demonstrate hyponatremia, although urinary salt losses appeared to be just as high, suggesting compensatory salt intake when the children are well. It is essential to monitor electrolytes and urinary losses to manage sickle crisis properly. Six to 11 mEq/kg/day of sodium is suggested as a usual need of these patients during crisis. Sickle cell disease patients have, in addition to the better known defect in concentration of urine, a functional defect in dilution of urine at least during periods of \"crisis\".", "contents": "Hyponatremia in sickle cell disease. A renal salt-losing state. Severe hyponatremia has been observed in three children with sickle cell disease, and mild hyponatremia was noted during 36% of random hospitalizations for sickle crisis secondary to vasoocclusion or infection. Serum and urinary electrolytes were therefore studied in such patients. Hyponatremia was found in 52% of patients hospitalized with pain and/or fever, even though they received large amounts of sodium intravenously. Urine sodium losses were high with frequent negative sodium balance and weight loss. When well, these patients did not demonstrate hyponatremia, although urinary salt losses appeared to be just as high, suggesting compensatory salt intake when the children are well. It is essential to monitor electrolytes and urinary losses to manage sickle crisis properly. Six to 11 mEq/kg/day of sodium is suggested as a usual need of these patients during crisis. Sickle cell disease patients have, in addition to the better known defect in concentration of urine, a functional defect in dilution of urine at least during periods of \"crisis\"."} {"id": "PMID:1271143", "title": "The significance of focal sclerotic lesions of glomeruli in children.", "content": "To establish the relationship between the type of focal sclerotic lesion of glomeruli and the development of progressive renal disease, the clinical courses of 20 children with focal segmental and 7 with focal global sclerosis were analyzed. Only five patients, all of them with focal segmental sclerosis, did not have the nephrotic syndrome, although all had proteinuria. Results suggest that patients with focal global sclerosis have a course identical to that of children with the minimal lesion form of nephrotic syndrome: onset in early childhood, response to steroid therapy, and a relapsing, nonprogressive course. Focal segmental sclerosis, in constrast, is characterized by older age at onset, high incidence of nephritic symptoms, lack of response to steroid therapy, and a progressive course with histologic and functional deterioration. Since most published reports have not distinguished between these two entities, a more favorable prognosis in focal segmental sclerosis may be inferred than is actually the case.", "contents": "The significance of focal sclerotic lesions of glomeruli in children. To establish the relationship between the type of focal sclerotic lesion of glomeruli and the development of progressive renal disease, the clinical courses of 20 children with focal segmental and 7 with focal global sclerosis were analyzed. Only five patients, all of them with focal segmental sclerosis, did not have the nephrotic syndrome, although all had proteinuria. Results suggest that patients with focal global sclerosis have a course identical to that of children with the minimal lesion form of nephrotic syndrome: onset in early childhood, response to steroid therapy, and a relapsing, nonprogressive course. Focal segmental sclerosis, in constrast, is characterized by older age at onset, high incidence of nephritic symptoms, lack of response to steroid therapy, and a progressive course with histologic and functional deterioration. Since most published reports have not distinguished between these two entities, a more favorable prognosis in focal segmental sclerosis may be inferred than is actually the case."} {"id": "PMID:1271148", "title": "Transient neonatal pustular melanosis.", "content": "Newborn infants were observed with vesicopustular and pigmented macular skin lesions, which occurred more commonly in black and mature infants and which were distinct clinically and histopathologically from erythema toxicum. Histopathology of skin biopsies of the vesicopustules is characterized by polymorphonuclear infiltration. The lesions often present as, or evolve into, a pigmented macule and persist from three weeks to three months. There are no associated systemic symptoms.", "contents": "Transient neonatal pustular melanosis. Newborn infants were observed with vesicopustular and pigmented macular skin lesions, which occurred more commonly in black and mature infants and which were distinct clinically and histopathologically from erythema toxicum. Histopathology of skin biopsies of the vesicopustules is characterized by polymorphonuclear infiltration. The lesions often present as, or evolve into, a pigmented macule and persist from three weeks to three months. There are no associated systemic symptoms."} {"id": "PMID:1271149", "title": "Renal function in respiratory distress syndrome.", "content": "Renal function wa assessed in 20 newborn infants with idiopathic respiratory distress syndrome and compared to that of 10 neonates without respiratory distress or renal disease. Inulin and PAH clearances were markedly depressed in neonates with RDS as compared to controls (5.9 +/- 0.6 vs 9.3 +/- 0.8 ml/min/m2 (p less than 0.01) and 13.5 +/- 2.0 vs 23.2 +/- 1.2 ml/min/m2 ( p less than 0.01), respectively). The impairment of inulin and PAH clearances correlated with the severity of the pulmonary disease. Improvement of the respiratory distress was followed by a progressive rise of inulin and PAH clearances toward normal values. Intravenous administration of hypertonic mannitol in three patients resulted in an immediate increase in urine flow and inulin and PAH clearances. It is concluded that a state of acute, reversible, renal insufficiency can occur in the acute phase of idiopathic respiratory distress syndrome.", "contents": "Renal function in respiratory distress syndrome. Renal function wa assessed in 20 newborn infants with idiopathic respiratory distress syndrome and compared to that of 10 neonates without respiratory distress or renal disease. Inulin and PAH clearances were markedly depressed in neonates with RDS as compared to controls (5.9 +/- 0.6 vs 9.3 +/- 0.8 ml/min/m2 (p less than 0.01) and 13.5 +/- 2.0 vs 23.2 +/- 1.2 ml/min/m2 ( p less than 0.01), respectively). The impairment of inulin and PAH clearances correlated with the severity of the pulmonary disease. Improvement of the respiratory distress was followed by a progressive rise of inulin and PAH clearances toward normal values. Intravenous administration of hypertonic mannitol in three patients resulted in an immediate increase in urine flow and inulin and PAH clearances. It is concluded that a state of acute, reversible, renal insufficiency can occur in the acute phase of idiopathic respiratory distress syndrome."} {"id": "PMID:1271151", "title": "Anxiety, self-concept, and personal and social adjustments in children with sickle cell anemia.", "content": "The psychologic effect of sickle cell anemia, a life-long chronic illness, on the self-concept, anxiety level, and personal and social adjustments of school-aged children was investigated by using a battery of standard psychologic tests. Two groups of children were evaluated: a study group of 29 children with sickle cell anemia (hemoglobin SS) and a comparison group of 26 black inner city schoolchildren without sickle cell disease or other known chronic illness. The youngsters with sickle cell anemia did not differ from a peer group of schoolchildren in personal, social, and total adjustments. The self-concept scores of the patient group were lower than those of the comparison group. An unexpected finding of the study was the observation that the anxiety scores (measuring acute anxiety) were significantly lower in the study group than those in the comparison group.", "contents": "Anxiety, self-concept, and personal and social adjustments in children with sickle cell anemia. The psychologic effect of sickle cell anemia, a life-long chronic illness, on the self-concept, anxiety level, and personal and social adjustments of school-aged children was investigated by using a battery of standard psychologic tests. Two groups of children were evaluated: a study group of 29 children with sickle cell anemia (hemoglobin SS) and a comparison group of 26 black inner city schoolchildren without sickle cell disease or other known chronic illness. The youngsters with sickle cell anemia did not differ from a peer group of schoolchildren in personal, social, and total adjustments. The self-concept scores of the patient group were lower than those of the comparison group. An unexpected finding of the study was the observation that the anxiety scores (measuring acute anxiety) were significantly lower in the study group than those in the comparison group."} {"id": "PMID:1271155", "title": "Pharmacokinetic analysis of the disposition of intravenous theophylline in young children.", "content": "The disposition of a single intravenous dose of theophylline, 3.2 mg/kg, was studied using a high-pressure liquid chromatographic assay in ten asthmatic children one to four years of age. The man plasma theophylline clearance was 0.100 +/- 0.036 l/kg/hr, kel 0.49 +/- 0.30 hr-1, betat1/2 3.38 +/- 1.11 hr, alphat1/2 0.13 +/- 0.09 hr, and V1 0.25 +/- 0.13 1/kg. Plasma theophylline clearance was approximately 40% greater in these children than that reported in adults, mainly due to an increased rate of drug elimination. Large interindividual differences were observed. Analysis of data using either a two- or one-compartment model yielded almost identical dosage regimens designed to rapidly achieve and maintain a chosen plasma theophylline concentration. Calculations based upon mean values of pharmacokinetic constants predict that a maintenance dose rate for aminophylline of 30 mg/kg/day, after a loading dose of 5.6 mg/kg, would rapidly achieve and maintain a mean steady-state plasma concentration of theophylline of 10 mg/1. Potential toxicity of such a regimen has not been excluded, since therapeutic trials (with achievement of steady state) have not yet been conducted.", "contents": "Pharmacokinetic analysis of the disposition of intravenous theophylline in young children. The disposition of a single intravenous dose of theophylline, 3.2 mg/kg, was studied using a high-pressure liquid chromatographic assay in ten asthmatic children one to four years of age. The man plasma theophylline clearance was 0.100 +/- 0.036 l/kg/hr, kel 0.49 +/- 0.30 hr-1, betat1/2 3.38 +/- 1.11 hr, alphat1/2 0.13 +/- 0.09 hr, and V1 0.25 +/- 0.13 1/kg. Plasma theophylline clearance was approximately 40% greater in these children than that reported in adults, mainly due to an increased rate of drug elimination. Large interindividual differences were observed. Analysis of data using either a two- or one-compartment model yielded almost identical dosage regimens designed to rapidly achieve and maintain a chosen plasma theophylline concentration. Calculations based upon mean values of pharmacokinetic constants predict that a maintenance dose rate for aminophylline of 30 mg/kg/day, after a loading dose of 5.6 mg/kg, would rapidly achieve and maintain a mean steady-state plasma concentration of theophylline of 10 mg/1. Potential toxicity of such a regimen has not been excluded, since therapeutic trials (with achievement of steady state) have not yet been conducted."} {"id": "PMID:1271156", "title": "Telephone assessment of illness by practicing pediatricians.", "content": "Telephone assessment of illness by 40 practicing pediatricians was studied using simulated complaints of cough, vomiting, diarrhea, or rash. Of a possible 370 standardized questions based on the American Academy of Pediatrics \"Guidelines for telephone communications,\" only 194 were used. Crucial questions such as difficulty breathing with cough, the state of hydration in diarrhea, the character of the eruption in rash, or the presence of abdominal pain with vomiting were asked less than 50% of the time. Pediatricians in practice for fewer than five years requested more information and spent more time on the telephone than did those with greater than five years' experience.", "contents": "Telephone assessment of illness by practicing pediatricians. Telephone assessment of illness by 40 practicing pediatricians was studied using simulated complaints of cough, vomiting, diarrhea, or rash. Of a possible 370 standardized questions based on the American Academy of Pediatrics \"Guidelines for telephone communications,\" only 194 were used. Crucial questions such as difficulty breathing with cough, the state of hydration in diarrhea, the character of the eruption in rash, or the presence of abdominal pain with vomiting were asked less than 50% of the time. Pediatricians in practice for fewer than five years requested more information and spent more time on the telephone than did those with greater than five years' experience."} {"id": "PMID:1271157", "title": "Passive euthanasia of defective newborn infants: legal considerations.", "content": "The recent increase in reporting of passive euthanasia of defective newborn infants has not been accompanied by extensive analysis of the legality of the practice or the appropriateness of current law. There appears to be criminal liability on several grounds for parents, physicians, nurses, and administrators. Such liability may include charges of homicide by omission, child neglect, and failure to report child neglect. Increasing public exposure of the practice increases the probability that such prosecutions may be brought. Individuals involved in such decisions should be aware of their possible legal liability. If existing legal policy is inappropriate, it sould be changed through open discussion and not subverted through private action. Two alternative policies are described: establishment of criteria for the class of infants who can be allowed to die or a better process of decision making. We conclude that a committment to process would be preferable.", "contents": "Passive euthanasia of defective newborn infants: legal considerations. The recent increase in reporting of passive euthanasia of defective newborn infants has not been accompanied by extensive analysis of the legality of the practice or the appropriateness of current law. There appears to be criminal liability on several grounds for parents, physicians, nurses, and administrators. Such liability may include charges of homicide by omission, child neglect, and failure to report child neglect. Increasing public exposure of the practice increases the probability that such prosecutions may be brought. Individuals involved in such decisions should be aware of their possible legal liability. If existing legal policy is inappropriate, it sould be changed through open discussion and not subverted through private action. Two alternative policies are described: establishment of criteria for the class of infants who can be allowed to die or a better process of decision making. We conclude that a committment to process would be preferable."} {"id": "PMID:1271169", "title": "Urinary biogenic amines in idiopathic apnea of prematurity.", "content": "Urinary biogenic amines were measured in 22 preterm infants of less than 36 weeks' gestational age. Fifteen of these infants had idiopathic apnea. Although levels of urinary dopa were not significantly different, dopamine, norepinephrine and epinephrine were all significantly lower in the infants with apena. It is proposed that apnea of prematurity may be related to an immaturity of catecholamine-producing pathways, leading to inadequate physiologic responses to hypoxia, with resulting accentuation of central respiratory depression. Alternatively, urinary biogenic amines may be a reflection of some unrelated process occurring elsewhere in the body or a depletion of catechol stores resulting from the apnea itself.", "contents": "Urinary biogenic amines in idiopathic apnea of prematurity. Urinary biogenic amines were measured in 22 preterm infants of less than 36 weeks' gestational age. Fifteen of these infants had idiopathic apnea. Although levels of urinary dopa were not significantly different, dopamine, norepinephrine and epinephrine were all significantly lower in the infants with apena. It is proposed that apnea of prematurity may be related to an immaturity of catecholamine-producing pathways, leading to inadequate physiologic responses to hypoxia, with resulting accentuation of central respiratory depression. Alternatively, urinary biogenic amines may be a reflection of some unrelated process occurring elsewhere in the body or a depletion of catechol stores resulting from the apnea itself."} {"id": "PMID:1271170", "title": "Amniotic fluid cortisol after premature rupture of membranes.", "content": "Total amniotic fluid cortisol concentration was studied in 12 patients at 24 to 34 weeks of gestation after premature rupture of membranes of one to eight days duration. Rupture of the membranes of less than 24 hours duration was associated with normal amniotic fluid cortisol concentrations. Rupture of membranes for more than 24 hours was associated in 10 of 12 patients with higher than normal amniotic fluid cortisol levels. The rise in amniotic fluid cortisol concentrations following premature rupture of the membranes may reflect increased fetal or maternal cortisol production or both, and could explain enhanced lung maturation in such infants.", "contents": "Amniotic fluid cortisol after premature rupture of membranes. Total amniotic fluid cortisol concentration was studied in 12 patients at 24 to 34 weeks of gestation after premature rupture of membranes of one to eight days duration. Rupture of the membranes of less than 24 hours duration was associated with normal amniotic fluid cortisol concentrations. Rupture of membranes for more than 24 hours was associated in 10 of 12 patients with higher than normal amniotic fluid cortisol levels. The rise in amniotic fluid cortisol concentrations following premature rupture of the membranes may reflect increased fetal or maternal cortisol production or both, and could explain enhanced lung maturation in such infants."} {"id": "PMID:1271171", "title": "Effect of premature delivery on the maturation of the Hering-Breuer inspiratory inhibitory reflex in human infants.", "content": "The Hering-Breuer inspiratory inhibitory reflex was studied serially in a group of premature infants and in a group of term infants in the immediate postnatal period. The premature infants had a stronger inspiratory inhibitory reflex than did the term infants at birth; this reflex decreased with maturation of the premature. Development in the extrauterine environment significantly delayed the rate of disappearance of this reflex. This may indicate that premature delivery retards the neurologic maturation of the human infant. The term infant showed no change in the activity of the inspiratory inhibitory reflex in the first five days of life.", "contents": "Effect of premature delivery on the maturation of the Hering-Breuer inspiratory inhibitory reflex in human infants. The Hering-Breuer inspiratory inhibitory reflex was studied serially in a group of premature infants and in a group of term infants in the immediate postnatal period. The premature infants had a stronger inspiratory inhibitory reflex than did the term infants at birth; this reflex decreased with maturation of the premature. Development in the extrauterine environment significantly delayed the rate of disappearance of this reflex. This may indicate that premature delivery retards the neurologic maturation of the human infant. The term infant showed no change in the activity of the inspiratory inhibitory reflex in the first five days of life."} {"id": "PMID:1271173", "title": "Hematologic abnormalities in severe neonatal necrotizing enterocolitis.", "content": "Serial determinations of the absolute granulocyte and platelet counts were performed in 40 infants with severe neonatal necrotizing enterocolitis. Fourteen of the 38 infants had absolute granulocyte counts less than 1,500 nm3, the mean absolute granulocyte count was significantly lower in the group of infants who died during the acute episode of NEC as compared to that of the infants who survived. Thrity-five of 40 infants had nadir platelet counts less than 150,000/nm3, clinical bleeding occurred in 12 of the thrombocytopenic infants. Fourteen thrombocytopenic infants were evaluated for disseminated intravascular coagulation by additional coagulation studies; six were noted to have laboratory evidence of DIC. We conclude that (1) a low absolute granulocyte count in severe NEC is associated with a poor prognosis and (2) thrombocytopenia is a significant problem in severe NEC and may occur with or without evidence of fulminant intravascular coagulation.", "contents": "Hematologic abnormalities in severe neonatal necrotizing enterocolitis. Serial determinations of the absolute granulocyte and platelet counts were performed in 40 infants with severe neonatal necrotizing enterocolitis. Fourteen of the 38 infants had absolute granulocyte counts less than 1,500 nm3, the mean absolute granulocyte count was significantly lower in the group of infants who died during the acute episode of NEC as compared to that of the infants who survived. Thrity-five of 40 infants had nadir platelet counts less than 150,000/nm3, clinical bleeding occurred in 12 of the thrombocytopenic infants. Fourteen thrombocytopenic infants were evaluated for disseminated intravascular coagulation by additional coagulation studies; six were noted to have laboratory evidence of DIC. We conclude that (1) a low absolute granulocyte count in severe NEC is associated with a poor prognosis and (2) thrombocytopenia is a significant problem in severe NEC and may occur with or without evidence of fulminant intravascular coagulation."} {"id": "PMID:1271174", "title": "Pharmacologic observations on the neonatal withdrawal syndrome.", "content": "The relationship between a maternal dose of methadone and the incidence and severity of neonatal signs of withdrawal, placental transfer of drug, and the relationship between maternal and neonatal plasma levels of methadone were studied in 30 mothers and their infants. Plasma levels of methadone were analyzed using a gas chromatographic method. Our studies demonstrate that the relationship between maternal dose of methadone and the incidence of neonatal withrawal symptoms was closely related to the last maternal dose of methadone. The ratio of neonatal to maternal plasma concentrations of methadone was 2.2:1. Neonatal withdrawal symptoms appear to be related to individual variation in maternal metabolism of the drug, placental transfer of methadone, and most importantly, to the individual variations in the rate of excretion of methadone as reflected in the neonatal plasma t 1/2. At plasma levels of methadone greater than or equal to 0.06 mug/ml, the symptomatic patients appeared to be protected from withdrawal. When the plasma concentration fell below this level, withdrawal symptoms began within 24 hours.", "contents": "Pharmacologic observations on the neonatal withdrawal syndrome. The relationship between a maternal dose of methadone and the incidence and severity of neonatal signs of withdrawal, placental transfer of drug, and the relationship between maternal and neonatal plasma levels of methadone were studied in 30 mothers and their infants. Plasma levels of methadone were analyzed using a gas chromatographic method. Our studies demonstrate that the relationship between maternal dose of methadone and the incidence of neonatal withrawal symptoms was closely related to the last maternal dose of methadone. The ratio of neonatal to maternal plasma concentrations of methadone was 2.2:1. Neonatal withdrawal symptoms appear to be related to individual variation in maternal metabolism of the drug, placental transfer of methadone, and most importantly, to the individual variations in the rate of excretion of methadone as reflected in the neonatal plasma t 1/2. At plasma levels of methadone greater than or equal to 0.06 mug/ml, the symptomatic patients appeared to be protected from withdrawal. When the plasma concentration fell below this level, withdrawal symptoms began within 24 hours."} {"id": "PMID:1271176", "title": "Genetic counseling for congenital heart disease.", "content": "The genetic knowledge of parents of children with congenital heart disease, who had received genetic counseling, was compared with that of a control noncounseled group attending the same cardiac clinic. A follow-up questionnaire showed that both groups had excellent knowledge of the nature of their children's heart lesions. The counseled group had significantly more accurate knowledge of their recurrence risks. Inasmuch as the reproductive attitudes of some of these parents were found to be influenced by genetic information, parents of children with CHD should be given a better understanding of recurrence risks for CHD than many of them possess.", "contents": "Genetic counseling for congenital heart disease. The genetic knowledge of parents of children with congenital heart disease, who had received genetic counseling, was compared with that of a control noncounseled group attending the same cardiac clinic. A follow-up questionnaire showed that both groups had excellent knowledge of the nature of their children's heart lesions. The counseled group had significantly more accurate knowledge of their recurrence risks. Inasmuch as the reproductive attitudes of some of these parents were found to be influenced by genetic information, parents of children with CHD should be given a better understanding of recurrence risks for CHD than many of them possess."} {"id": "PMID:1271190", "title": "Histocompatibility antigens in childhood-onset arthritis.", "content": "One hundred and twelve well-studied patients with a prior diagnosis of juvenile rheumatoid arthritis were differentiated into seven clinically distinct subgroups, including a group in whom recognizable ankylosing spondylitis had developed by time of follow-up. An apparent increased prevalence of HLA-B27 in the entire series (26%) was clearly related to its increased prevalence in only two subgroups: patients whose disease had progressed to overt ankylosing spondylitis (five of five patients) and boys with pauciarticular arthritis whose disease would be consistent with early ankylosing spondylitis (11 of 18 patients). There were no significant associations of B27 with systemic onset JRA, polyarticular JRA, pauciarticular JRA in girls, or JRA with chronic iridocyclitis. The only other significant alterations found were increased prevalences of HLA-A2 and HLA-BW15 in patients with polyarticular disease without identifiable rheumatoid factor. This study emphasizes that the clinical disorders included under the category of juvenile rheumatoid arthritis represent more than a single disease and that this heterogeneity must be considered in interpreting studies such as those of histocompatibility typing.", "contents": "Histocompatibility antigens in childhood-onset arthritis. One hundred and twelve well-studied patients with a prior diagnosis of juvenile rheumatoid arthritis were differentiated into seven clinically distinct subgroups, including a group in whom recognizable ankylosing spondylitis had developed by time of follow-up. An apparent increased prevalence of HLA-B27 in the entire series (26%) was clearly related to its increased prevalence in only two subgroups: patients whose disease had progressed to overt ankylosing spondylitis (five of five patients) and boys with pauciarticular arthritis whose disease would be consistent with early ankylosing spondylitis (11 of 18 patients). There were no significant associations of B27 with systemic onset JRA, polyarticular JRA, pauciarticular JRA in girls, or JRA with chronic iridocyclitis. The only other significant alterations found were increased prevalences of HLA-A2 and HLA-BW15 in patients with polyarticular disease without identifiable rheumatoid factor. This study emphasizes that the clinical disorders included under the category of juvenile rheumatoid arthritis represent more than a single disease and that this heterogeneity must be considered in interpreting studies such as those of histocompatibility typing."} {"id": "PMID:1271191", "title": "Encephalopathy following measles infection in children with chronic illness.", "content": "Five patients with an unusual encephalopathy, possible secondary to measles virus infection, are described. Features common to these patients are: an existing chronic disease, neurologic deterioration 2 1/2 to 6 months after a measles infection, and death several weeks later. These events occurred when the chronic disease (e.g. leukemia or neuroblastoma) was in remission. That the measles virus was the causative agent is suggested only by finding in brain and extracranial tissues intracytoplasmic and intranuclear inclusions which contained measleslike particles. Additional clinical features seen in each of the five patients were: seizures, hypertension, and the inappropriate secretion of antidiuretic hormone.", "contents": "Encephalopathy following measles infection in children with chronic illness. Five patients with an unusual encephalopathy, possible secondary to measles virus infection, are described. Features common to these patients are: an existing chronic disease, neurologic deterioration 2 1/2 to 6 months after a measles infection, and death several weeks later. These events occurred when the chronic disease (e.g. leukemia or neuroblastoma) was in remission. That the measles virus was the causative agent is suggested only by finding in brain and extracranial tissues intracytoplasmic and intranuclear inclusions which contained measleslike particles. Additional clinical features seen in each of the five patients were: seizures, hypertension, and the inappropriate secretion of antidiuretic hormone."} {"id": "PMID:1271192", "title": "Good diabetic control - a study in mass delusion.", "content": "The terms \"diabetic control\" and \"diabetic management\" are not synonymous. Diabetic control implies normal glucose metabolism, typically monitored by periodic determinations of plasma glucose and urine reducing sugar concentrations. A group of 220 diabetic children attending a camp complied 74% of the time with the request to collect and test their urine for URS. Fifty percent of random URS values determined by the children varied from those obtained on the same specimens of urine by laboratory technicians. Good diabetic control defined URS less than 25gm/24 hours was found in 18 of 54 children.", "contents": "Good diabetic control - a study in mass delusion. The terms \"diabetic control\" and \"diabetic management\" are not synonymous. Diabetic control implies normal glucose metabolism, typically monitored by periodic determinations of plasma glucose and urine reducing sugar concentrations. A group of 220 diabetic children attending a camp complied 74% of the time with the request to collect and test their urine for URS. Fifty percent of random URS values determined by the children varied from those obtained on the same specimens of urine by laboratory technicians. Good diabetic control defined URS less than 25gm/24 hours was found in 18 of 54 children."} {"id": "PMID:1271193", "title": "Modular Formula: an approach to management of infants with specific or complex food intolerances.", "content": "Modular Formula is a dietary preparation for use in treating infants with complex malabsorptive disorders and for weaning infants from total parenteral nutrition. With this formula the physician can alter the quality of the various nutrients normally fed to infants as well as concentrations of those nutrients. Infants who cannot tolerate existing proprietary formulas will often thrive with the judicious use of this flexible formula. Modular Formula provides the clinician with a useful aid in the diagnosis and treatment of chronic diarrhea of infancy.", "contents": "Modular Formula: an approach to management of infants with specific or complex food intolerances. Modular Formula is a dietary preparation for use in treating infants with complex malabsorptive disorders and for weaning infants from total parenteral nutrition. With this formula the physician can alter the quality of the various nutrients normally fed to infants as well as concentrations of those nutrients. Infants who cannot tolerate existing proprietary formulas will often thrive with the judicious use of this flexible formula. Modular Formula provides the clinician with a useful aid in the diagnosis and treatment of chronic diarrhea of infancy."} {"id": "PMID:1271194", "title": "Congenital hypothyroidism in a young man with growth hormone, thyrotropin, and prolactin deficiencies.", "content": "A growth-retarded, mentally deficient, young man is described with diminished secretory response of growth hormone, thyrotropin, and prolactin to the pharmacologic stimuli of insulin, arginine, chlorpromazine, and thyrotropin-releasing hormone. Gonadotropin and ACTH functions were normal both basically and upon pharmacologic stimulation. Additionally, the patient was unresponsive to exogenous thyrotropin injections. These data suggest that the hypothyroidism in this patient was due to combined thyroid dysgenesis and pituitary insufficiency, i.e., primary and secondary hypothyroidism.", "contents": "Congenital hypothyroidism in a young man with growth hormone, thyrotropin, and prolactin deficiencies. A growth-retarded, mentally deficient, young man is described with diminished secretory response of growth hormone, thyrotropin, and prolactin to the pharmacologic stimuli of insulin, arginine, chlorpromazine, and thyrotropin-releasing hormone. Gonadotropin and ACTH functions were normal both basically and upon pharmacologic stimulation. Additionally, the patient was unresponsive to exogenous thyrotropin injections. These data suggest that the hypothyroidism in this patient was due to combined thyroid dysgenesis and pituitary insufficiency, i.e., primary and secondary hypothyroidism."} {"id": "PMID:1271195", "title": "Interrupted aortic arch in infancy.", "content": "Data from 30 infants with interrupted aortic arch in the New England Regional Infant Cardiac Program, 1968 to 1974, were reviewed. All patients had major associated cardiac abnormalities: approximately one third had ventricular septal defect with patent ductus arteriosus, one third had complex ventricular septal defect with left ventricular outflow obstruction, and one third had complex intracardiac lesions incompatible with survival. Twenty-one of the patients had either palliative or reconstructive surgery, with a hospital mortality rate of 76%. Nine patients did not have surgery; eight of them died at a median age of four days. One-stage primary repair of interrupted aortic arch including the associated cardiac defects, using deep hypothermia and circulatory arrest, is proposed as the current method of treatment in such infants.", "contents": "Interrupted aortic arch in infancy. Data from 30 infants with interrupted aortic arch in the New England Regional Infant Cardiac Program, 1968 to 1974, were reviewed. All patients had major associated cardiac abnormalities: approximately one third had ventricular septal defect with patent ductus arteriosus, one third had complex ventricular septal defect with left ventricular outflow obstruction, and one third had complex intracardiac lesions incompatible with survival. Twenty-one of the patients had either palliative or reconstructive surgery, with a hospital mortality rate of 76%. Nine patients did not have surgery; eight of them died at a median age of four days. One-stage primary repair of interrupted aortic arch including the associated cardiac defects, using deep hypothermia and circulatory arrest, is proposed as the current method of treatment in such infants."} {"id": "PMID:1271196", "title": "Craniosynostosis, midfacial hypoplasia and foot abnormalities: an autosomal dominant phenotype in a large Amish kindred.", "content": "An unusual spectrum of craniofacial and foot abnormalities has been detected within a large midwestern Amish kindred. Enlarged great toes and craniofacial abnormalities suggested Pfeiffer acrocephalosynadactyly type V; however, thumb abnormalities were not present. Eighty-eight affected individuals were observed and another 50 were reliably reported to be affected. An autosomal dominant inheritance pattern was observed associated with variable expressivity. All affected individuals had some clinical or radiologic abnormality of the feet. The phenotypic expression was so variable that the entire spectrum of dominantly inherited craniofacial dysotoses-acrocephalosyndactylys (except the typical Apert syndrome) was seen within this kindred.", "contents": "Craniosynostosis, midfacial hypoplasia and foot abnormalities: an autosomal dominant phenotype in a large Amish kindred. An unusual spectrum of craniofacial and foot abnormalities has been detected within a large midwestern Amish kindred. Enlarged great toes and craniofacial abnormalities suggested Pfeiffer acrocephalosynadactyly type V; however, thumb abnormalities were not present. Eighty-eight affected individuals were observed and another 50 were reliably reported to be affected. An autosomal dominant inheritance pattern was observed associated with variable expressivity. All affected individuals had some clinical or radiologic abnormality of the feet. The phenotypic expression was so variable that the entire spectrum of dominantly inherited craniofacial dysotoses-acrocephalosyndactylys (except the typical Apert syndrome) was seen within this kindred."} {"id": "PMID:1271204", "title": "A neurologic comparison of pre-term and full-term infants at term conceptional age.", "content": "There are currently no neurologic examinations designed for pre-term infants with sufficient data to determine neurologic deviance at various gestational or conceptional ages (gestational age plus age from birth). In this study a neurologic examination standardized for full-term newborn infants was administered to 97 full-term newborn infants was administered to 97 full-term newborn infants and 97 pre-term infants at their expected date of birth, 40 weeks' conceptional age. The pre-term infants had more weak responses than did the full-term infants despite being at a higher level of activity state throughout the examination. The pre-term infants also had more asymmetric responses. There was no correlation between gestational age and the incidence of weak responses in the pre-term infants, but the pre-term infants of lowest birth weight at all gestational ages had the greatest number of weak responses. The latter may be because pregnancy and neonatal problems contribute more to the neurologic findings than does the length of gestation.", "contents": "A neurologic comparison of pre-term and full-term infants at term conceptional age. There are currently no neurologic examinations designed for pre-term infants with sufficient data to determine neurologic deviance at various gestational or conceptional ages (gestational age plus age from birth). In this study a neurologic examination standardized for full-term newborn infants was administered to 97 full-term newborn infants was administered to 97 full-term newborn infants and 97 pre-term infants at their expected date of birth, 40 weeks' conceptional age. The pre-term infants had more weak responses than did the full-term infants despite being at a higher level of activity state throughout the examination. The pre-term infants also had more asymmetric responses. There was no correlation between gestational age and the incidence of weak responses in the pre-term infants, but the pre-term infants of lowest birth weight at all gestational ages had the greatest number of weak responses. The latter may be because pregnancy and neonatal problems contribute more to the neurologic findings than does the length of gestation."} {"id": "PMID:1271207", "title": "Complexity and measurement of hypnotic susceptibility: a comment on Coe and Sarbin's alternative interpretation.", "content": "Coe and Sarbin's claim that a single role skill dimension accounts for individual differences in hypnotizability is not supported by an empirical analysis. We suggest that current measures of hypnotic susceptibility are not only factorially complex but contain a sizable nonhypnotic variance component. Implications for the assessment of \"true\" hypnotic susceptibility are discussed.", "contents": "Complexity and measurement of hypnotic susceptibility: a comment on Coe and Sarbin's alternative interpretation. Coe and Sarbin's claim that a single role skill dimension accounts for individual differences in hypnotizability is not supported by an empirical analysis. We suggest that current measures of hypnotic susceptibility are not only factorially complex but contain a sizable nonhypnotic variance component. Implications for the assessment of \"true\" hypnotic susceptibility are discussed."} {"id": "PMID:1271208", "title": "The Honi phenomenon revisited: factors underlying the resistance to perceptual distortion of one's partner.", "content": "An individual being viewed in an Ames room usually appears considerably altered in physical size to an observer. However, some married persons perceive less size distortion of their spouses than a stranger. This instance of selective perceptual distortion, known as the Honi phenomenon, could perhaps reflect differential familiarity and/or emotional involvement toward these stimulus persons. Using heterosexual couples as subjects, we investigated familiarity (i.e., length of the relationship), type of relationship (i.e., dating, engaged, or married), and positive cathexis (i.e., love, liking, and trust of one's partner) as possible mediators of this effect and also explored the impact of some judgemental variations. Neither familiarity nor type of relationship influenced relative perceptual distortion of partner versus stranger. Rather, selective perceptual distortion was directly related to the strength of positive cathexis, principally among females. Only women high in positive cathexis exhibited the Honi phenomenon and perceived a stranger as being more distorted than their partners. In contrast, size judgements by men were affected only by the sequence in which stimulus persons were observed. Implications and interpretations of these findings are discussed.", "contents": "The Honi phenomenon revisited: factors underlying the resistance to perceptual distortion of one's partner. An individual being viewed in an Ames room usually appears considerably altered in physical size to an observer. However, some married persons perceive less size distortion of their spouses than a stranger. This instance of selective perceptual distortion, known as the Honi phenomenon, could perhaps reflect differential familiarity and/or emotional involvement toward these stimulus persons. Using heterosexual couples as subjects, we investigated familiarity (i.e., length of the relationship), type of relationship (i.e., dating, engaged, or married), and positive cathexis (i.e., love, liking, and trust of one's partner) as possible mediators of this effect and also explored the impact of some judgemental variations. Neither familiarity nor type of relationship influenced relative perceptual distortion of partner versus stranger. Rather, selective perceptual distortion was directly related to the strength of positive cathexis, principally among females. Only women high in positive cathexis exhibited the Honi phenomenon and perceived a stranger as being more distorted than their partners. In contrast, size judgements by men were affected only by the sequence in which stimulus persons were observed. Implications and interpretations of these findings are discussed."} {"id": "PMID:1271209", "title": "Self-disclosure: an attributional perspective.", "content": "This experiment examined the effect of timing of an intimate disclosure and assignment of responsibility for the event disclosed on interpersonal attraction. Subjects were induced to interact with a confederate who in all cases revealed something quite personal about himself. The disclosure occurred either early or near the end of a 10-minute conversation. The confederate accepted responsibility for the event disclosed, did not mention responsibility, or assigned responsibility to external factors. Negative traits were assigned to the early disclosure, and he was liked significantly less than the late discloser. The results are explained in terms of differential attributions made to early and late disclosures. The results for the assignment of responsibility variable were surprising: The confederate who accepted responsibility for the event disclosed elicited more negative reactions than the confederate who blamed other factors or who did not mention responsibility. Some possible reasons for this unexpected finding are discussed.", "contents": "Self-disclosure: an attributional perspective. This experiment examined the effect of timing of an intimate disclosure and assignment of responsibility for the event disclosed on interpersonal attraction. Subjects were induced to interact with a confederate who in all cases revealed something quite personal about himself. The disclosure occurred either early or near the end of a 10-minute conversation. The confederate accepted responsibility for the event disclosed, did not mention responsibility, or assigned responsibility to external factors. Negative traits were assigned to the early disclosure, and he was liked significantly less than the late discloser. The results are explained in terms of differential attributions made to early and late disclosures. The results for the assignment of responsibility variable were surprising: The confederate who accepted responsibility for the event disclosed elicited more negative reactions than the confederate who blamed other factors or who did not mention responsibility. Some possible reasons for this unexpected finding are discussed."} {"id": "PMID:1271210", "title": "Multidimensional locus of control in sociopolitical activists of conservative and liberal ideologies.", "content": "Three studies were conducted to examine the relationship between a multi-dimensional measure of locus of control and sociopolitical activism, controlling for the effects of political ideology. In Study 1, 98 male college students completed a measure of conservatism-liberalism. Kerpelman's Activism scale, and locus of control scales designed to differentiate between two types of externals: belief in powerful others versus belief in chance forces. In Studies 2 and 3, female college students (Ns=26 and 40) who differed in the extent of their participation in leftist political activities or feminist causes responded to the multidimensional locus of control scales. As predicted, results from analyses of variance and trend analyses indicate that for liberals, increases in expectancies of control by powerful others are positively associated with increases in activism, while for conservatives, there is a negative relationship. The importance of controlling for ideology and the implications of the differentiated view of externality for understanding social action are discussed.", "contents": "Multidimensional locus of control in sociopolitical activists of conservative and liberal ideologies. Three studies were conducted to examine the relationship between a multi-dimensional measure of locus of control and sociopolitical activism, controlling for the effects of political ideology. In Study 1, 98 male college students completed a measure of conservatism-liberalism. Kerpelman's Activism scale, and locus of control scales designed to differentiate between two types of externals: belief in powerful others versus belief in chance forces. In Studies 2 and 3, female college students (Ns=26 and 40) who differed in the extent of their participation in leftist political activities or feminist causes responded to the multidimensional locus of control scales. As predicted, results from analyses of variance and trend analyses indicate that for liberals, increases in expectancies of control by powerful others are positively associated with increases in activism, while for conservatives, there is a negative relationship. The importance of controlling for ideology and the implications of the differentiated view of externality for understanding social action are discussed."} {"id": "PMID:1271211", "title": "Biographical determinants of achieved eminence: a multivariate approach to the Cox data.", "content": "Ranked eminence of creators and leaders was hypothesized to be a function of both substantive (developmental and productive) variables and methodological artifacts. Cox's sample of 301 geniuses was reexamined using multiple-regression techniques. The results indicated that ranked eminence is (a) a curvilinear inverted-U function of education for creators but a negative linear function for leaders, (b) a positive linear function of versatility for leaders only, and (c) a curvilinear U-shaped function of life span for creators but a \"backwards-J\" function for leaders. Although creators are more intelligent than leaders, the correlation that Cox found between intelligence and ranked eminence was shown to be an artifact of data reliability and, especially, a timewise sampling bias. It was also shown that father's status has no direct impact on ranked eminence.", "contents": "Biographical determinants of achieved eminence: a multivariate approach to the Cox data. Ranked eminence of creators and leaders was hypothesized to be a function of both substantive (developmental and productive) variables and methodological artifacts. Cox's sample of 301 geniuses was reexamined using multiple-regression techniques. The results indicated that ranked eminence is (a) a curvilinear inverted-U function of education for creators but a negative linear function for leaders, (b) a positive linear function of versatility for leaders only, and (c) a curvilinear U-shaped function of life span for creators but a \"backwards-J\" function for leaders. Although creators are more intelligent than leaders, the correlation that Cox found between intelligence and ranked eminence was shown to be an artifact of data reliability and, especially, a timewise sampling bias. It was also shown that father's status has no direct impact on ranked eminence."} {"id": "PMID:1271212", "title": "Aggression and heat: the influence of ambient temperature, negative affect, and a cooling drink on physical aggression.", "content": "Two experiments were conducted to examine the influence of ambient temperature upon physical aggression. In the first, male subjects received either a positive or negative evaluation from a confederate and were then provided with an opportunity to agress against this person by means of electric shock. On the basis of previous research, it was predicted that high ambient temperatures (92-95 degrees F) would facilitate aggression by those receiving positive evaluations but actually inhibit such behavior by those receiving negative assessments. Results confirmed both of these predictions and also indicated that more moderate but still uncomfortably warm temperatures (82-85 degrees F) produced similar effects. The second experiment employed procedures similar to the first and examined the suggestion that administration of a cooling drink would reduce the impact of high ambient temperatures upon overt aggression. This prediction, too, was confirmed. The possible mediating role of negative affect with respect to the influence of ambient temperature and other environmental factors upon aggression was discussed.", "contents": "Aggression and heat: the influence of ambient temperature, negative affect, and a cooling drink on physical aggression. Two experiments were conducted to examine the influence of ambient temperature upon physical aggression. In the first, male subjects received either a positive or negative evaluation from a confederate and were then provided with an opportunity to agress against this person by means of electric shock. On the basis of previous research, it was predicted that high ambient temperatures (92-95 degrees F) would facilitate aggression by those receiving positive evaluations but actually inhibit such behavior by those receiving negative assessments. Results confirmed both of these predictions and also indicated that more moderate but still uncomfortably warm temperatures (82-85 degrees F) produced similar effects. The second experiment employed procedures similar to the first and examined the suggestion that administration of a cooling drink would reduce the impact of high ambient temperatures upon overt aggression. This prediction, too, was confirmed. The possible mediating role of negative affect with respect to the influence of ambient temperature and other environmental factors upon aggression was discussed."} {"id": "PMID:1271213", "title": "Causal priority of social desirability over self-concept: a cross-lagged correlation analysis.", "content": "The study examined the causal relationship between social desirability (SD) and self-concept (SC). Two self-report instruments--Crandall's Children's Social Desirability Scale and the Piers-Harris Children's Self-Concept Scale--were administered before and after a 9-month therapeutic treatment designed to enhance self-concept. Subjects were 57 upper elementary pupils in a laboratory research school. Three hypotheses were proposed: (a) There is a positive correlation between SD and SC; (b) SD is more stable across time than SC; and (c) SD is causally prior to SC. Cross-lagged panel correlation analysis supported all three hypotheses. Discussion centers on a causal explanation of the distorting effect of SD upon SC scores.", "contents": "Causal priority of social desirability over self-concept: a cross-lagged correlation analysis. The study examined the causal relationship between social desirability (SD) and self-concept (SC). Two self-report instruments--Crandall's Children's Social Desirability Scale and the Piers-Harris Children's Self-Concept Scale--were administered before and after a 9-month therapeutic treatment designed to enhance self-concept. Subjects were 57 upper elementary pupils in a laboratory research school. Three hypotheses were proposed: (a) There is a positive correlation between SD and SC; (b) SD is more stable across time than SC; and (c) SD is causally prior to SC. Cross-lagged panel correlation analysis supported all three hypotheses. Discussion centers on a causal explanation of the distorting effect of SD upon SC scores."} {"id": "PMID:1271214", "title": "Achievement and morality: a cross-cultural analysis of causal attribution and evaluation.", "content": "A recent study by Weiner and Peter has considered the emergence of certain patterns of attribution and evaluation in achievement and moral situations. According to their analysis, judgments should generally follow a Piagetian sequence in which younger children are influenced more by the outcome of an episode and older children by the intent of the protagonist. With a sample of U.S. subjects they found overall support for this analysis. A major of the present study is to determine how sociocultural factors may influence the judgmental patterns outlined by Weiner and Peter by essentially replicating their study in the manifestly different cultural context provided in Iran. Important discrepancies with Weiner and Peter were found which can be attributed to sociocultural factors. However, the cognitive-developmental framework proved generally valuable in working toward a comparative understanding of socialization patterns extant in the two cultures.", "contents": "Achievement and morality: a cross-cultural analysis of causal attribution and evaluation. A recent study by Weiner and Peter has considered the emergence of certain patterns of attribution and evaluation in achievement and moral situations. According to their analysis, judgments should generally follow a Piagetian sequence in which younger children are influenced more by the outcome of an episode and older children by the intent of the protagonist. With a sample of U.S. subjects they found overall support for this analysis. A major of the present study is to determine how sociocultural factors may influence the judgmental patterns outlined by Weiner and Peter by essentially replicating their study in the manifestly different cultural context provided in Iran. Important discrepancies with Weiner and Peter were found which can be attributed to sociocultural factors. However, the cognitive-developmental framework proved generally valuable in working toward a comparative understanding of socialization patterns extant in the two cultures."} {"id": "PMID:1271215", "title": "Externality in the nonobese: effects of environmental responsiveness on weight.", "content": "The study considered whether external responsiveness in normal weight people would predict changes in eating behavior and weight following major alteration of environmetnal food cues. Normal weight children were tested for externality on measures of eating, slide recall, and extremity of affective responsiveness during the first week of a summer camp, and were weighed biweekly thereafter. There was a significant correlation between externality and weight change, indicating that the more externally responsive the children were, the more weight they gained. The implications of this finding for theories about the development of obesity were considered.", "contents": "Externality in the nonobese: effects of environmental responsiveness on weight. The study considered whether external responsiveness in normal weight people would predict changes in eating behavior and weight following major alteration of environmetnal food cues. Normal weight children were tested for externality on measures of eating, slide recall, and extremity of affective responsiveness during the first week of a summer camp, and were weighed biweekly thereafter. There was a significant correlation between externality and weight change, indicating that the more externally responsive the children were, the more weight they gained. The implications of this finding for theories about the development of obesity were considered."} {"id": "PMID:1271216", "title": "Effects of nonverbal dissimulation on emotional experience and autonomic arousal.", "content": "Three studies are reported that examine the relationship between the nonverbal display of emotional affect and indices of the emotional state. Subjects were asked either to conceal or to exaggerate the facial display associated with the anticipation and reception of painful shocks that varied in intensity. Both self-reports of shock painfulness and skin conductance measures of emotional response showed significant changes paralleling the changes induced in expressive behavior; that is, the suppression of expressive responses decreased the magnitude of phasic skin conductance changes and subjective reports of painfulness as compared to the free expression or exaggeration of pain-related expressive response. The effects were obtained for shocks of varying intensities and for both male and female subjects. The findings support theories of emotion that assume that expressive responses serve a self-regulatory as well as a social-communicative function, and further suggest that the self-regulation is mediated neurally, rather than via a process of self-attribution. Finally, the results highlight the need for research on dissimulation in social interaction to consider the effects of acting upon the actor, as well as its effects upon the inferences of observers.", "contents": "Effects of nonverbal dissimulation on emotional experience and autonomic arousal. Three studies are reported that examine the relationship between the nonverbal display of emotional affect and indices of the emotional state. Subjects were asked either to conceal or to exaggerate the facial display associated with the anticipation and reception of painful shocks that varied in intensity. Both self-reports of shock painfulness and skin conductance measures of emotional response showed significant changes paralleling the changes induced in expressive behavior; that is, the suppression of expressive responses decreased the magnitude of phasic skin conductance changes and subjective reports of painfulness as compared to the free expression or exaggeration of pain-related expressive response. The effects were obtained for shocks of varying intensities and for both male and female subjects. The findings support theories of emotion that assume that expressive responses serve a self-regulatory as well as a social-communicative function, and further suggest that the self-regulation is mediated neurally, rather than via a process of self-attribution. Finally, the results highlight the need for research on dissimulation in social interaction to consider the effects of acting upon the actor, as well as its effects upon the inferences of observers."} {"id": "PMID:1271217", "title": "Psychometric, diurnal, and electrophysiological correlates of activation.", "content": "Several studies were performed using Thayer's Activation-Deactivation Adjective Check List (AD-ACL). Factor analysis of college students' scores identified a single activation factor representing a continuum ranging from sleep through wakefulness. Next, changes over the diurnal cycle in activation factor scores were demonstrated. One-week test-retest reliability was also investigated. Finally, activation scores were related to pulse rate, respiration rate, and skin resistance level under passive and active conditions. Correlations between factor scores and electrophysiological measures were higher than were intercorrelations of electrophysiological measures, indicating that scores on this revised activation factor represent a valid measure of phenomenological bodily activation level.", "contents": "Psychometric, diurnal, and electrophysiological correlates of activation. Several studies were performed using Thayer's Activation-Deactivation Adjective Check List (AD-ACL). Factor analysis of college students' scores identified a single activation factor representing a continuum ranging from sleep through wakefulness. Next, changes over the diurnal cycle in activation factor scores were demonstrated. One-week test-retest reliability was also investigated. Finally, activation scores were related to pulse rate, respiration rate, and skin resistance level under passive and active conditions. Correlations between factor scores and electrophysiological measures were higher than were intercorrelations of electrophysiological measures, indicating that scores on this revised activation factor represent a valid measure of phenomenological bodily activation level."} {"id": "PMID:1271218", "title": "The perception of self and others: acquaintanceship, affect, and actor-observer differences.", "content": "Three studies were designed to examine how people perceive themselves versus others. The main finding was that people were seen as causing positive behaviors, and situational factors were regarded as causing negative behaviors (positivity effect). This positivity effect was found to operate most strongly for perceptions of intimate others, such as spouse and friends, and less strongly for strangers and liked and disliked acquaintances. There was little support for the actor-observer difference that people view their own behavior more situationally than they do other people's behavior. It was concluded that both cognitive and motivational factors must be considered in predicting how people perceive and describe others.", "contents": "The perception of self and others: acquaintanceship, affect, and actor-observer differences. Three studies were designed to examine how people perceive themselves versus others. The main finding was that people were seen as causing positive behaviors, and situational factors were regarded as causing negative behaviors (positivity effect). This positivity effect was found to operate most strongly for perceptions of intimate others, such as spouse and friends, and less strongly for strangers and liked and disliked acquaintances. There was little support for the actor-observer difference that people view their own behavior more situationally than they do other people's behavior. It was concluded that both cognitive and motivational factors must be considered in predicting how people perceive and describe others."} {"id": "PMID:1271219", "title": "Egotism and attribution.", "content": "Egotism is defined as the tendency to make attributions that put oneself in the best possible light, for example, the attribution of good outcomes to one's skill rather than to luck. An experiment was designed to demonstrate egotism. To rule out alternative explanations, the experiment compared the attributions of actors and observers for both good and bad outcomes. Theoretical considerations suggested that egotism might be especially likely at the conclusion of competition. Hence, subjects competed, won, or lost and then made attributions for their own and their opponents' outcomes. Evidence for egotism was clear. In addition, subjects made predictions of their opponents' attributions, which often turned out to be fairly accurate.", "contents": "Egotism and attribution. Egotism is defined as the tendency to make attributions that put oneself in the best possible light, for example, the attribution of good outcomes to one's skill rather than to luck. An experiment was designed to demonstrate egotism. To rule out alternative explanations, the experiment compared the attributions of actors and observers for both good and bad outcomes. Theoretical considerations suggested that egotism might be especially likely at the conclusion of competition. Hence, subjects competed, won, or lost and then made attributions for their own and their opponents' outcomes. Evidence for egotism was clear. In addition, subjects made predictions of their opponents' attributions, which often turned out to be fairly accurate."} {"id": "PMID:1271220", "title": "The coronary-prone behavior pattern and the suppression of fatigue on a treadmill test.", "content": "A study was conducted to test the hypothesis that Type A (coronary-prone) individuals would show greater suppression of subjective fatigue than Type B (non-coronary-prone) individuals in order to persist at a tiring but challenging task. Type A and Type B college students completed a Balke treadmill test (at a walking pace) while rating their fatigue at 2-minute intervals. Each subject also completed another treadmill test (at a running pace) that was designed to assess maximum aerobic capacity. Subjects' aerobic capacities and their aerobic performance levels attained on the Balke test were determined by analysis of expired air. Each subject's walking performance was scored as a proportion of his maximum aerobic capacity. Analysis of the resulting percentage values indicated greater effort among A's than B's. Moreover, the subjective fatigue ratings of A's were lower than those of B's. The results were discussed in terms of fatigue suppression as an instrumental response for attaining mastery over the environment. consideration was also given to the role of fatigue in the onset of coronary heart disease.", "contents": "The coronary-prone behavior pattern and the suppression of fatigue on a treadmill test. A study was conducted to test the hypothesis that Type A (coronary-prone) individuals would show greater suppression of subjective fatigue than Type B (non-coronary-prone) individuals in order to persist at a tiring but challenging task. Type A and Type B college students completed a Balke treadmill test (at a walking pace) while rating their fatigue at 2-minute intervals. Each subject also completed another treadmill test (at a running pace) that was designed to assess maximum aerobic capacity. Subjects' aerobic capacities and their aerobic performance levels attained on the Balke test were determined by analysis of expired air. Each subject's walking performance was scored as a proportion of his maximum aerobic capacity. Analysis of the resulting percentage values indicated greater effort among A's than B's. Moreover, the subjective fatigue ratings of A's were lower than those of B's. The results were discussed in terms of fatigue suppression as an instrumental response for attaining mastery over the environment. consideration was also given to the role of fatigue in the onset of coronary heart disease."} {"id": "PMID:1271221", "title": "Interpersonal attraction and rewarding aspects of disclosure content and level.", "content": "The relationship between self-disclosure and interpersonal attraction was viewed within the context of theories of social penetration and social exchange. The effects of similarity of disclosure level and similarity in content of disclosure on interpersonal attraction were assessed. Specifically, 24 high-self-disclosing subjects and 24 low-self-disclosing subjects were presented with four bogus inventories manipulated on the variables of agreement in content and amount of disclosure. The reward potential of various factors within the disclosure process were measured by the subject's attraction to these four hypothetical strangers. Results indicated that along with amount of disclosure, similarity in the content of the disclosed material and similarity between the subject's and another's level of disclosure had a positive influence on attraction.", "contents": "Interpersonal attraction and rewarding aspects of disclosure content and level. The relationship between self-disclosure and interpersonal attraction was viewed within the context of theories of social penetration and social exchange. The effects of similarity of disclosure level and similarity in content of disclosure on interpersonal attraction were assessed. Specifically, 24 high-self-disclosing subjects and 24 low-self-disclosing subjects were presented with four bogus inventories manipulated on the variables of agreement in content and amount of disclosure. The reward potential of various factors within the disclosure process were measured by the subject's attraction to these four hypothetical strangers. Results indicated that along with amount of disclosure, similarity in the content of the disclosed material and similarity between the subject's and another's level of disclosure had a positive influence on attraction."} {"id": "PMID:1271222", "title": "Effects of prior destructive behavior, anonymity, and group presence on deindividuation and aggression.", "content": "Three of Zimbardo's deindividuation input variables (group presence, anonymity, and arousal) were manipulated in laboratory experiment, and their effects on aggression and deindividuation were measured. Only arousal produced a significant increase in aggression (p less than .05), while group presence produced a significant decrease in aggression (p less than .01). Anonymity had no significant effect on subjects' aggressiveness. Deindividuation per se was measured on a postsession questionnaire that assessed subjects' memory for their own aggressive behavior, self-consciousness, concern for social evaluation, and memory for central and peripheral cues. Only arousal condition participants showed deindividuation changes, but a factor analysis revealed that the deindividuation changes did not comprise a unified factor. Also it did not appear that the internal changes caused aggressive behavior, since the correlation between the two was low.", "contents": "Effects of prior destructive behavior, anonymity, and group presence on deindividuation and aggression. Three of Zimbardo's deindividuation input variables (group presence, anonymity, and arousal) were manipulated in laboratory experiment, and their effects on aggression and deindividuation were measured. Only arousal produced a significant increase in aggression (p less than .05), while group presence produced a significant decrease in aggression (p less than .01). Anonymity had no significant effect on subjects' aggressiveness. Deindividuation per se was measured on a postsession questionnaire that assessed subjects' memory for their own aggressive behavior, self-consciousness, concern for social evaluation, and memory for central and peripheral cues. Only arousal condition participants showed deindividuation changes, but a factor analysis revealed that the deindividuation changes did not comprise a unified factor. Also it did not appear that the internal changes caused aggressive behavior, since the correlation between the two was low."} {"id": "PMID:1271223", "title": "Learned helplessness, depression, and the attribution of failure.", "content": "Depressed and nondepressed college students received experience with solvable, unsolvable, or no discrimination problems. When later tested on a series of patterned anagrams, depressed groups performed worse than nondepressed groups, and unsolvable groups performed worse than solvable and control groups. As predicted by the learned helplessness model of depression, nondepressed subjects given unsolvable problems showed anagram deficits parallel to those found in naturally occurring depression. When depressed subjects attributed their failure to the difficulty of the problems rather than to their own incompetence, performance improved strikingly. So, failure in itself is apparently not sufficient to produce helplessness deficits in man, but failure that leads to a decreased belief in personal competence is sufficient.", "contents": "Learned helplessness, depression, and the attribution of failure. Depressed and nondepressed college students received experience with solvable, unsolvable, or no discrimination problems. When later tested on a series of patterned anagrams, depressed groups performed worse than nondepressed groups, and unsolvable groups performed worse than solvable and control groups. As predicted by the learned helplessness model of depression, nondepressed subjects given unsolvable problems showed anagram deficits parallel to those found in naturally occurring depression. When depressed subjects attributed their failure to the difficulty of the problems rather than to their own incompetence, performance improved strikingly. So, failure in itself is apparently not sufficient to produce helplessness deficits in man, but failure that leads to a decreased belief in personal competence is sufficient."} {"id": "PMID:1271224", "title": "Personal space invasions in the lavatory: suggestive evidence for arousal.", "content": "The hypothesis that personal space invasions produce arousal was investigated in a field experiment. A men's lavatory provided a setting where norms for privacy were salient, where personal space invasions could occur in the case of men urinating, where the opportunity for compensatory responses to invasion were minimal, and where proximity-induced arousal could be measured. Research on micturation indicates that social stressors inhibit relaxation of the external urethral sphincter, which would delay the onset of micturation, and that they increase intravesical pressure, which would shorten the duration of micturation once begun. Sixty lavatory users were randomly assigned to one of three levels of interpersonal distance and their micturation times were recorded. In a three-urinal lavatory, a confederate stood immediately adjacent to a subject, one urinal removed, or was absent. Paralleling the results of a correlational pilot study, close interpersonal distances increased the delay of onset and decreased the persistence of micturation. These findings provide objective evidence that personal space invasions produce physiological changes associated with arousal.", "contents": "Personal space invasions in the lavatory: suggestive evidence for arousal. The hypothesis that personal space invasions produce arousal was investigated in a field experiment. A men's lavatory provided a setting where norms for privacy were salient, where personal space invasions could occur in the case of men urinating, where the opportunity for compensatory responses to invasion were minimal, and where proximity-induced arousal could be measured. Research on micturation indicates that social stressors inhibit relaxation of the external urethral sphincter, which would delay the onset of micturation, and that they increase intravesical pressure, which would shorten the duration of micturation once begun. Sixty lavatory users were randomly assigned to one of three levels of interpersonal distance and their micturation times were recorded. In a three-urinal lavatory, a confederate stood immediately adjacent to a subject, one urinal removed, or was absent. Paralleling the results of a correlational pilot study, close interpersonal distances increased the delay of onset and decreased the persistence of micturation. These findings provide objective evidence that personal space invasions produce physiological changes associated with arousal."} {"id": "PMID:1271225", "title": "Effects of control and predictability on the physical and psychological well-being of the institutionalized aged.", "content": "It was hypothesized that some of the characteristics frequently observed among the aged--such as feelings of depression and helphlessness, as well as accelerated physical decline--are at least in part attributable to loss of control. A field experiment in which institutionalized aged were randomly assigned to one of four conditions was carried out to assess the effects of increased control and predictability upon the physical and psychological well-being of the aged. Individuals in three of the four conditions were visited by college undergraduates under varying contingencies, while persons in the fourth condition were not visited and served as a baseline comparison group. Subjects in the control condition could determine both the frequency and duration of visits they recieved. A second group of subjects (predict) was informed when they would be visited and how long the visitor would stay, but had no control over these details. A third group (random) was visited on a random schedule. It was found that predictable and controllable positive events have a powerful positive impact upon the well-being of the institutionalized aged.", "contents": "Effects of control and predictability on the physical and psychological well-being of the institutionalized aged. It was hypothesized that some of the characteristics frequently observed among the aged--such as feelings of depression and helphlessness, as well as accelerated physical decline--are at least in part attributable to loss of control. A field experiment in which institutionalized aged were randomly assigned to one of four conditions was carried out to assess the effects of increased control and predictability upon the physical and psychological well-being of the aged. Individuals in three of the four conditions were visited by college undergraduates under varying contingencies, while persons in the fourth condition were not visited and served as a baseline comparison group. Subjects in the control condition could determine both the frequency and duration of visits they recieved. A second group of subjects (predict) was informed when they would be visited and how long the visitor would stay, but had no control over these details. A third group (random) was visited on a random schedule. It was found that predictable and controllable positive events have a powerful positive impact upon the well-being of the institutionalized aged."} {"id": "PMID:1271226", "title": "Ares and Babbitt in the classroom: effects of competition and reward on children's aggression.", "content": "In many competitive situations, aggression is one of several instrumental behaviors that can produce reinforcing consequences. Despite the fact that aggression precipitated by competition for valued resources is an increasingly important social problem, there is little evidence of a causal relationship. In a factorial experiment, dyads of 64 kindergarten and first-grade males played a game in a face-to-face setting that yielded a prize for the winner only. It was predicted that high levels of competition and high levels of reward magnitude would produce more aggressive behavior than lower levels of these variables. Additionally, children rated by their teachers as high in dispositional aggressiveness were anticipated to behave most aggressively in the game. Each of these predictions was confirmed on three different measures of aggression: verbal, interference, and physical. Furthermore, the data suggested that constructive action was sometimes abandoned in attempts to harm an opponent. Since competition for desirable objects is a social reality, it was concluded that conditions inhibiting aggression in these situations should be investigated.", "contents": "Ares and Babbitt in the classroom: effects of competition and reward on children's aggression. In many competitive situations, aggression is one of several instrumental behaviors that can produce reinforcing consequences. Despite the fact that aggression precipitated by competition for valued resources is an increasingly important social problem, there is little evidence of a causal relationship. In a factorial experiment, dyads of 64 kindergarten and first-grade males played a game in a face-to-face setting that yielded a prize for the winner only. It was predicted that high levels of competition and high levels of reward magnitude would produce more aggressive behavior than lower levels of these variables. Additionally, children rated by their teachers as high in dispositional aggressiveness were anticipated to behave most aggressively in the game. Each of these predictions was confirmed on three different measures of aggression: verbal, interference, and physical. Furthermore, the data suggested that constructive action was sometimes abandoned in attempts to harm an opponent. Since competition for desirable objects is a social reality, it was concluded that conditions inhibiting aggression in these situations should be investigated."} {"id": "PMID:1271227", "title": "Effects of a stimulus associated with a victim's pain on later aggression.", "content": "Male college students participated in an experiment designed to associate a neutral stimulus with a victim's pain and then to assess the impact of the paired stimulus on their aggression. The subjects were either provoked or not provoked by a confederate's shock evaluation. They then observed a flashing white light that was associated with either their former evaluator's pain or an irrelevant, affectively neutral event. The subjects then administered electric shocks to a different confederate, with whom they had not interacted previously, at the flash of both the familiar white light (the conditioned stimulus) and a novel blue light. Results supported the prediction that provoked subjects would give more intense shocks to the conditioned stimulus when it had been associated with their evaluator's pain. Unprovoked subjects were found to give less intense shocks to the light that had been associated with their evaluator's pain.", "contents": "Effects of a stimulus associated with a victim's pain on later aggression. Male college students participated in an experiment designed to associate a neutral stimulus with a victim's pain and then to assess the impact of the paired stimulus on their aggression. The subjects were either provoked or not provoked by a confederate's shock evaluation. They then observed a flashing white light that was associated with either their former evaluator's pain or an irrelevant, affectively neutral event. The subjects then administered electric shocks to a different confederate, with whom they had not interacted previously, at the flash of both the familiar white light (the conditioned stimulus) and a novel blue light. Results supported the prediction that provoked subjects would give more intense shocks to the conditioned stimulus when it had been associated with their evaluator's pain. Unprovoked subjects were found to give less intense shocks to the light that had been associated with their evaluator's pain."} {"id": "PMID:1271228", "title": "Evidence of stress as a function of experimentally altered appraisal of stimulus aversiveness and coping adequacy.", "content": "The present study examined the effects of initial appraisal of stimulus aversiveness and coping adequacy on subsequent evidence of stress. Results indicated that level of appraised coping efficacy had the most pronounced effect during stressor exposure and that the pattern of this effect was dependent on whether the source of the appraised coping resources was \"personal\" (the subject's own resources) or \"environmental\" (a bogus technique donated by the experimenter). In addition, information about personal resources reduced the pre- to poststressor increment in state anxiety and lessened cognitive avoidance of stressor-related stimuli. Results were discussed with respect to differential sensitivity of components of stress response to variation in environmental versus personal sources of coping efficacy, and the specific aspects of cognitive structuring associated with variation in physiological reaction (muscle tension) were noted. The importance of factors associated with appraised coping efficacy was clearly supported, but factors involving the objective (in contrast to defensive) aspects of appraised stressor potency required further investigation, and suggestions for such future research were made.", "contents": "Evidence of stress as a function of experimentally altered appraisal of stimulus aversiveness and coping adequacy. The present study examined the effects of initial appraisal of stimulus aversiveness and coping adequacy on subsequent evidence of stress. Results indicated that level of appraised coping efficacy had the most pronounced effect during stressor exposure and that the pattern of this effect was dependent on whether the source of the appraised coping resources was \"personal\" (the subject's own resources) or \"environmental\" (a bogus technique donated by the experimenter). In addition, information about personal resources reduced the pre- to poststressor increment in state anxiety and lessened cognitive avoidance of stressor-related stimuli. Results were discussed with respect to differential sensitivity of components of stress response to variation in environmental versus personal sources of coping efficacy, and the specific aspects of cognitive structuring associated with variation in physiological reaction (muscle tension) were noted. The importance of factors associated with appraised coping efficacy was clearly supported, but factors involving the objective (in contrast to defensive) aspects of appraised stressor potency required further investigation, and suggestions for such future research were made."} {"id": "PMID:1271229", "title": "Person perception and the Berkowitz paradigm for the study of aggression.", "content": "Three experiments in person perception were conducted to investigate the conditions under which naive observers label an actor as aggressive and to ascertain how this label affects the reactions of the observers to the actor. These studies were performed by exposing subjects to written descriptions of Berkowitz's much-used paradigm for the study of aggression in order to additionally demonstrate that naive observers do not label in the same way as do research psychologists. In Experiment 1 the hypothesis was confirmed that harm-doing behavior is labeled as aggression only when it is antinormative. When harm doing was justified by the instigation or attack of another person, its use did not lead to the actor being labeled as aggressive. In Experiment 2 it was found that violation of the limits imposed by the experimenter on the number of shocks that could be used by actors led observers to characterize them as aggressive even when their action was justified by the prior instigation of the other party. Violation of two norms led to a more aggressive rating of the actor than did the violation of only one norm. Experiment 3 showed that actors who are labeled as aggressive are disapproved of and avoided by observers. The results of these studies are discussed in terms of the ecological validity of Berkowitz's research paradigm and metatheoretical implications for the scientific study of harm-doing behavior.", "contents": "Person perception and the Berkowitz paradigm for the study of aggression. Three experiments in person perception were conducted to investigate the conditions under which naive observers label an actor as aggressive and to ascertain how this label affects the reactions of the observers to the actor. These studies were performed by exposing subjects to written descriptions of Berkowitz's much-used paradigm for the study of aggression in order to additionally demonstrate that naive observers do not label in the same way as do research psychologists. In Experiment 1 the hypothesis was confirmed that harm-doing behavior is labeled as aggression only when it is antinormative. When harm doing was justified by the instigation or attack of another person, its use did not lead to the actor being labeled as aggressive. In Experiment 2 it was found that violation of the limits imposed by the experimenter on the number of shocks that could be used by actors led observers to characterize them as aggressive even when their action was justified by the prior instigation of the other party. Violation of two norms led to a more aggressive rating of the actor than did the violation of only one norm. Experiment 3 showed that actors who are labeled as aggressive are disapproved of and avoided by observers. The results of these studies are discussed in terms of the ecological validity of Berkowitz's research paradigm and metatheoretical implications for the scientific study of harm-doing behavior."} {"id": "PMID:1271230", "title": "Collective coping with stress: group reactions to fear, anxiety, and ambiguity.", "content": "A review of studies examining the fear-affiliation relationship revealed that none had ever observed groups in interaction while awaiting a fearful event. It was predicted that such groups would, consistent with individual member's previously studied affiliative preferences, spend more time interacting in the service of social comparison needs than would groups facing anxiety or ambiguity. This prediction was strongly supported, and in addition, it was found, as expected, that groups in the fear condition developed a relatively high degree of cohesiveness as measured by intragroup attraction ratings. The implication of these results for the interpretation of the functional relationship between stress and cohesiveness was discussed.", "contents": "Collective coping with stress: group reactions to fear, anxiety, and ambiguity. A review of studies examining the fear-affiliation relationship revealed that none had ever observed groups in interaction while awaiting a fearful event. It was predicted that such groups would, consistent with individual member's previously studied affiliative preferences, spend more time interacting in the service of social comparison needs than would groups facing anxiety or ambiguity. This prediction was strongly supported, and in addition, it was found, as expected, that groups in the fear condition developed a relatively high degree of cohesiveness as measured by intragroup attraction ratings. The implication of these results for the interpretation of the functional relationship between stress and cohesiveness was discussed."} {"id": "PMID:1271231", "title": "Effects of self-esteem and expected duration of interaction on liking for a highly rewarding partner.", "content": "Psychological theories predicated on the assumption of human selfishness and theories based on principles of equity may lead to conflicting predictions about when a person will like his partner. Of special interest are a person's reactions to receiving uncommonly high rewards. The present study addressed this issue by examing the development of same-sex liking in 40 female college students. It was hypothesized that subjects with lowered self-esteem, having a great need for interpersonal rewards, would react favorably to the receipt of such rewards, even if underserved. Subjects with raised self-esteem, on the other hand, having had their need for rewards met, should respond unfavorably to the receipt of high rewards, desiring a more equitable distribution of reward. These effects should be strong only when continuing dyadic interaction is expected (i.e., as issues of stability and reciprocity become salient). The predictions were confirmed.", "contents": "Effects of self-esteem and expected duration of interaction on liking for a highly rewarding partner. Psychological theories predicated on the assumption of human selfishness and theories based on principles of equity may lead to conflicting predictions about when a person will like his partner. Of special interest are a person's reactions to receiving uncommonly high rewards. The present study addressed this issue by examing the development of same-sex liking in 40 female college students. It was hypothesized that subjects with lowered self-esteem, having a great need for interpersonal rewards, would react favorably to the receipt of such rewards, even if underserved. Subjects with raised self-esteem, on the other hand, having had their need for rewards met, should respond unfavorably to the receipt of high rewards, desiring a more equitable distribution of reward. These effects should be strong only when continuing dyadic interaction is expected (i.e., as issues of stability and reciprocity become salient). The predictions were confirmed."} {"id": "PMID:1271232", "title": "Arbitrary norms and social change in high- and low-authoritarian societies.", "content": "Following Jacobs and Campbell's methodology for replacing confederates and naive subjects over 11 successive generations, this study considered the impact of authoritarianism on the rate of social change of arbitrary norms in laboratory societies. Subjects were 116 college students scoring high and low on the California F scale who participated in an autokinetic experiment either with no confederates (control), confederates who made estimates in a range of 9 to 15 inches (22.86-38.10 cm) (moderately arbitrary), or those who estimated in a range of 15 to 21 inches (38.10--53.34 cm) (extremely arbitrary). Results indicated: (a) High-F societies perpetuated arbitrary norms (both 9-15 and 15-21) for more generations than low-F societies; (b) in low-F societies, the 9-15- and 15-21-inch norms rapidly declined; and (c) in high-F societies, the 15-21-inch norms gradually declined, while the 9-15-inch norm declined very little. Overall, the results suggested that an interaction model would better described social change than do presently existing theories of social change.", "contents": "Arbitrary norms and social change in high- and low-authoritarian societies. Following Jacobs and Campbell's methodology for replacing confederates and naive subjects over 11 successive generations, this study considered the impact of authoritarianism on the rate of social change of arbitrary norms in laboratory societies. Subjects were 116 college students scoring high and low on the California F scale who participated in an autokinetic experiment either with no confederates (control), confederates who made estimates in a range of 9 to 15 inches (22.86-38.10 cm) (moderately arbitrary), or those who estimated in a range of 15 to 21 inches (38.10--53.34 cm) (extremely arbitrary). Results indicated: (a) High-F societies perpetuated arbitrary norms (both 9-15 and 15-21) for more generations than low-F societies; (b) in low-F societies, the 9-15- and 15-21-inch norms rapidly declined; and (c) in high-F societies, the 15-21-inch norms gradually declined, while the 9-15-inch norm declined very little. Overall, the results suggested that an interaction model would better described social change than do presently existing theories of social change."} {"id": "PMID:1271233", "title": "A renewed look at Miller's conflict theory of aggression displacement.", "content": "The present study is the first to examine Miller's theoretical assumptions of displaced aggression using human subjects. Subjects in the present study either served as nonangered controls, were angered by the experimenter's confederate, or were both angered by and led to fear the confederate. All subjects were then able to three targets: the confederate, a person described as a friend of the confederate, and a person having no association with the confederate. Targets received the most intense aggression from angered subjects. The difference between the aggression gradients for high-anger-low-fear and control subject. Frightened subjects gave their most intense aggression to the displaced targets. Results also support the suggestion that direct aggression is most likely if the aggressor can first extinguish some of his fear by attacking more indirect targets.", "contents": "A renewed look at Miller's conflict theory of aggression displacement. The present study is the first to examine Miller's theoretical assumptions of displaced aggression using human subjects. Subjects in the present study either served as nonangered controls, were angered by the experimenter's confederate, or were both angered by and led to fear the confederate. All subjects were then able to three targets: the confederate, a person described as a friend of the confederate, and a person having no association with the confederate. Targets received the most intense aggression from angered subjects. The difference between the aggression gradients for high-anger-low-fear and control subject. Frightened subjects gave their most intense aggression to the displaced targets. Results also support the suggestion that direct aggression is most likely if the aggressor can first extinguish some of his fear by attacking more indirect targets."} {"id": "PMID:1271234", "title": "Trait salience in the spontaneous self-concept.", "content": "A discrimination theory of selective perception was used to predict that a given trait would be spontaneously salient in a person's self-concept to the exten that this trait was distinctive for the person within her or his social groups. Sixth-grade students' general and physical spontaneous self-concepts were elicited in their classroom settings. The distinctiveness within the classroom of each student's characteristics on each of a variety of dimensions was determined, and it was found that in a majority of cases the dimension was significantly more salient in the spontaneous self-concepts of those students whose characteristic on thedimension was more distinctive. Also reported are incidental findings which include a description of the contents of spontaneous self-comcepts as well as determinants of their length and of the spontaneous mention of one's sex as part of one's self-concept.", "contents": "Trait salience in the spontaneous self-concept. A discrimination theory of selective perception was used to predict that a given trait would be spontaneously salient in a person's self-concept to the exten that this trait was distinctive for the person within her or his social groups. Sixth-grade students' general and physical spontaneous self-concepts were elicited in their classroom settings. The distinctiveness within the classroom of each student's characteristics on each of a variety of dimensions was determined, and it was found that in a majority of cases the dimension was significantly more salient in the spontaneous self-concepts of those students whose characteristic on thedimension was more distinctive. Also reported are incidental findings which include a description of the contents of spontaneous self-comcepts as well as determinants of their length and of the spontaneous mention of one's sex as part of one's self-concept."} {"id": "PMID:1271235", "title": "Verbal imagery and connotation as memory-induced mediators of aggressive behavior.", "content": "Three studies investigated the effects of an information-processing variable (imagery-concreteness) on susceptibility to aggressive stimulation. Study 1 (n=83) results indicated that subjects' rating of imagery level and aggressive connotation for words can be manipulated independently. In study 2 (n=64), manipulations of verbal connotation and verbal imagery indicated that imagery level but not aggressive connotation significantly influenced the delayed recall of the verbal material. In Study 3 (n=60), males in a 2 X 2 between-subjects factorial design first learned lists of words varying in imagery (high or low) and verbal connotation (aggressive or neutral). Next, subjects were given the opportunity to shock their partners as part of a sham learning task. To induce arousal, all subjects learning high-imagery-aggressive word lists delivered significantly more intense shock to their partners. The results were interpreted as supporting an information-processing (memory) analysis of the effects of exposure to aggressive material.", "contents": "Verbal imagery and connotation as memory-induced mediators of aggressive behavior. Three studies investigated the effects of an information-processing variable (imagery-concreteness) on susceptibility to aggressive stimulation. Study 1 (n=83) results indicated that subjects' rating of imagery level and aggressive connotation for words can be manipulated independently. In study 2 (n=64), manipulations of verbal connotation and verbal imagery indicated that imagery level but not aggressive connotation significantly influenced the delayed recall of the verbal material. In Study 3 (n=60), males in a 2 X 2 between-subjects factorial design first learned lists of words varying in imagery (high or low) and verbal connotation (aggressive or neutral). Next, subjects were given the opportunity to shock their partners as part of a sham learning task. To induce arousal, all subjects learning high-imagery-aggressive word lists delivered significantly more intense shock to their partners. The results were interpreted as supporting an information-processing (memory) analysis of the effects of exposure to aggressive material."} {"id": "PMID:1271236", "title": "Information about the model's unconditioned stimulus and response in vicarious classical conditioning.", "content": "Four groups with 16 observers each participated in a differential, vicarious conditioning experiment with skin conductance responses as the dependent variable. The information available to the observer about the model's unconditioned stimulus and response was varied in a 2 X 2 factorial design. Results clearly showed that information about the model's unconditioned stimulus (a high or low dB level) was not necessary for vicarious instigation, but that information about the unconditioned response (a high or low emotional aversiveness) was necessary. Data for conditioning of responses showed almost identical patterns to those for vicarious instigation. To explain the results, a distinction between factors necessary for the development and elicitation of vicariously instigated responses was introduced, and the effectiveness of information about the model's response on the elicitation of vicariously instigated responses was considered in terms of an expansion of Bandura's social learning theory.", "contents": "Information about the model's unconditioned stimulus and response in vicarious classical conditioning. Four groups with 16 observers each participated in a differential, vicarious conditioning experiment with skin conductance responses as the dependent variable. The information available to the observer about the model's unconditioned stimulus and response was varied in a 2 X 2 factorial design. Results clearly showed that information about the model's unconditioned stimulus (a high or low dB level) was not necessary for vicarious instigation, but that information about the unconditioned response (a high or low emotional aversiveness) was necessary. Data for conditioning of responses showed almost identical patterns to those for vicarious instigation. To explain the results, a distinction between factors necessary for the development and elicitation of vicariously instigated responses was introduced, and the effectiveness of information about the model's response on the elicitation of vicariously instigated responses was considered in terms of an expansion of Bandura's social learning theory."} {"id": "PMID:1271237", "title": "Machiavellianism in patients and their children.", "content": "The role of the family in the development of Machiavellianism was examined in this study. High- and low-Machiavellian sixth graders played a bluffing game. Their parents completed Machiavellian belief measures. The Machiavellianism of fathers and mothers was positively related to their children's success at deceiving others but not at seeing through others' attempts at deception. In addition, fathers' Machiavellianism was positively related to their children's Machiavellian beliefs. These data support a modeling hypothesis for the development of Machiavellianism. Unexpectedly, the children's own behaviors and beliefs were unrelated. This pattern of results suggests that a child's manipulative behaviors and beliefs are learned separately and only become consistent over time.", "contents": "Machiavellianism in patients and their children. The role of the family in the development of Machiavellianism was examined in this study. High- and low-Machiavellian sixth graders played a bluffing game. Their parents completed Machiavellian belief measures. The Machiavellianism of fathers and mothers was positively related to their children's success at deceiving others but not at seeing through others' attempts at deception. In addition, fathers' Machiavellianism was positively related to their children's Machiavellian beliefs. These data support a modeling hypothesis for the development of Machiavellianism. Unexpectedly, the children's own behaviors and beliefs were unrelated. This pattern of results suggests that a child's manipulative behaviors and beliefs are learned separately and only become consistent over time."} {"id": "PMID:1271244", "title": "Controlled drug release from polymeric delivery devices IV: in vitro--in vivo correlation of subcutaneous release of norgestomet from hydrophilic implants.", "content": "The in vitro and in vivo releases of norgestomet from hydrophilic implants were found to follow a matrix-controlled (Q - t1/2) process. The sorption of drug onto the implants was observed to obey the same mechanism but with a much smaller magnitide of the Q/t1/2 value. The effect of the extent of cross-linking on the magnitude of drug release (Q/t1/2) profiles was analyzed both theoretically and experimentally. The release of norgestomet from hydrophilic implants was found to be an energy-linked process. Two energy terms were calculated; the activation energy for matrix diffusion was 7.71 kcal/mole, and the heat of drug crystal solvation was 25-28.6 kcal/mole.", "contents": "Controlled drug release from polymeric delivery devices IV: in vitro--in vivo correlation of subcutaneous release of norgestomet from hydrophilic implants. The in vitro and in vivo releases of norgestomet from hydrophilic implants were found to follow a matrix-controlled (Q - t1/2) process. The sorption of drug onto the implants was observed to obey the same mechanism but with a much smaller magnitide of the Q/t1/2 value. The effect of the extent of cross-linking on the magnitude of drug release (Q/t1/2) profiles was analyzed both theoretically and experimentally. The release of norgestomet from hydrophilic implants was found to be an energy-linked process. Two energy terms were calculated; the activation energy for matrix diffusion was 7.71 kcal/mole, and the heat of drug crystal solvation was 25-28.6 kcal/mole."} {"id": "PMID:1271245", "title": "Modification of diffusion rates of benzocaine from topical vehicles using sodium salicylate as complexing agent.", "content": "The release of benzocaine from various topical vehicles containing benzocaine, alone and in the presence of a complexing agent, sodium salicylate, was measured at 37 degrees using dialysis through a cellulose membrane. Sodium salicylate had a marked effect on the release of benzocaine, depending upon the the type of vehicle, with the largest increase observed for the water-miscible base, polyethylene glycol (macrogol ointment BPC). The amount of drug released from preparations containing 1% (w/w) and 2% (w/w) benzocaine in this vehicle depended upon the sodium salicylate concentration. Results are discussed in terms of the differing physical properties of the complexes formed.", "contents": "Modification of diffusion rates of benzocaine from topical vehicles using sodium salicylate as complexing agent. The release of benzocaine from various topical vehicles containing benzocaine, alone and in the presence of a complexing agent, sodium salicylate, was measured at 37 degrees using dialysis through a cellulose membrane. Sodium salicylate had a marked effect on the release of benzocaine, depending upon the the type of vehicle, with the largest increase observed for the water-miscible base, polyethylene glycol (macrogol ointment BPC). The amount of drug released from preparations containing 1% (w/w) and 2% (w/w) benzocaine in this vehicle depended upon the sodium salicylate concentration. Results are discussed in terms of the differing physical properties of the complexes formed."} {"id": "PMID:1271246", "title": "Release and elimination of 14C-fluphenazine enanthate and decanoate esters administered in sesame oil to dogs.", "content": "The rates of release of 14C-fluphenazine enanthate and 14C-fluphenazine decanoate were compared in two groups of five male dogs. Each dog was given a single dose (2 mg/kg im) of either the enanthate or decanoate ester in sesame oil. The times required to attain maximum concentrations of radioactivity in plasma were 3.8 +/- 0.5 days (+/-SE) for the enanthate ester and 10.6 +/- 1.1 days for the decanoate ester (p less than 0.001); maximum concentrations of radioactivity in the plasma at these times were 16.7 +/- 1.1 and 11.1 +/- 1.2 ng/ml, respectively (p less than 0.01). However, 35 days after dosing, the concentrations of radioactivity in plasma were greater for the decanoate ester than for the enanthate ester. The times required for 50% of the dose to be excreted in the urine and feces were 7.8 +/- 0.5 days for the enanthate ester and 22.6 +/- 4.4 days for the decanoate ester (p less than 0.05). The total amounts excreted in 35 days were 85.4 +/- 1.8 and 68.8 +/- 6.6% of the dose for the enanthate and decanoate esters, respectively; the average half-times for the rates of release of radioactivity from depot and body, as calculated from the data for total excretion, were 5.55 days for the enanthate ester and 15.4 days for the decanoate ester. Thirty-five days after dosing, the amount of the dose present in the injection site was 4.6 +/- 1.6% for the enanthate ester and 18.6 +/- 5.7% for the decanoate ester. Two groups of six dogs each were protected against the emetic effects of apomorphine more than twice as long by the decanoate ester than by the enanthate ester after the subcutaneous administration of single 8-mg/kg doses of either drug in sesame oil (p less than 0.05). Based on measurements of total radioactivity, it was concluded that the decanoate ester was released from the depot at less than one-half the rate of the enanthate ester.", "contents": "Release and elimination of 14C-fluphenazine enanthate and decanoate esters administered in sesame oil to dogs. The rates of release of 14C-fluphenazine enanthate and 14C-fluphenazine decanoate were compared in two groups of five male dogs. Each dog was given a single dose (2 mg/kg im) of either the enanthate or decanoate ester in sesame oil. The times required to attain maximum concentrations of radioactivity in plasma were 3.8 +/- 0.5 days (+/-SE) for the enanthate ester and 10.6 +/- 1.1 days for the decanoate ester (p less than 0.001); maximum concentrations of radioactivity in the plasma at these times were 16.7 +/- 1.1 and 11.1 +/- 1.2 ng/ml, respectively (p less than 0.01). However, 35 days after dosing, the concentrations of radioactivity in plasma were greater for the decanoate ester than for the enanthate ester. The times required for 50% of the dose to be excreted in the urine and feces were 7.8 +/- 0.5 days for the enanthate ester and 22.6 +/- 4.4 days for the decanoate ester (p less than 0.05). The total amounts excreted in 35 days were 85.4 +/- 1.8 and 68.8 +/- 6.6% of the dose for the enanthate and decanoate esters, respectively; the average half-times for the rates of release of radioactivity from depot and body, as calculated from the data for total excretion, were 5.55 days for the enanthate ester and 15.4 days for the decanoate ester. Thirty-five days after dosing, the amount of the dose present in the injection site was 4.6 +/- 1.6% for the enanthate ester and 18.6 +/- 5.7% for the decanoate ester. Two groups of six dogs each were protected against the emetic effects of apomorphine more than twice as long by the decanoate ester than by the enanthate ester after the subcutaneous administration of single 8-mg/kg doses of either drug in sesame oil (p less than 0.05). Based on measurements of total radioactivity, it was concluded that the decanoate ester was released from the depot at less than one-half the rate of the enanthate ester."} {"id": "PMID:1271247", "title": "Analysis of butaclamol in serum by fluorescence induction.", "content": "A sensitive TLC-fluorometric method was developed for the analysis of butaclamol, a benzo[6,7]cyclohepta[1,2,3-de]-pyrido[2,1-a]isoquinoline derivative, in serum. The method involves cyclohexane extraction of serum samples followed by TLC of the concentrated extracts. The developed TLC plates were sprayed with an oxidizing reagent and heated at 110 degrees. Highly fluorescent spots were produced for butaclamol, which was well separated from metabolites and serum components. Fluorometric densitometry permitted quantitation with a sensitivity of 10 ng/spot application.", "contents": "Analysis of butaclamol in serum by fluorescence induction. A sensitive TLC-fluorometric method was developed for the analysis of butaclamol, a benzo[6,7]cyclohepta[1,2,3-de]-pyrido[2,1-a]isoquinoline derivative, in serum. The method involves cyclohexane extraction of serum samples followed by TLC of the concentrated extracts. The developed TLC plates were sprayed with an oxidizing reagent and heated at 110 degrees. Highly fluorescent spots were produced for butaclamol, which was well separated from metabolites and serum components. Fluorometric densitometry permitted quantitation with a sensitivity of 10 ng/spot application."} {"id": "PMID:1271248", "title": "Bioavailability assessment under quasi- and nonsteady-state conditions II: study designs.", "content": "The flexibility of bioavailability assessment at quasi-and nonsteady state is demonstrated by systematically removing experimental constraints from the study design. Mathematical expressions are derived to describe each design variation. From the resultant solutions, it is evident that the proposed method can accommodate nonuniformities in dose, dosage interval, dosage regimen, dosing cycle, sampling interval, plasma half-life, washout period, and protocol adherence. Nominal requirements for the method are linear kinetics and mean plasma concentrations estimated over time intervals beginning and ending in the log-linear region.", "contents": "Bioavailability assessment under quasi- and nonsteady-state conditions II: study designs. The flexibility of bioavailability assessment at quasi-and nonsteady state is demonstrated by systematically removing experimental constraints from the study design. Mathematical expressions are derived to describe each design variation. From the resultant solutions, it is evident that the proposed method can accommodate nonuniformities in dose, dosage interval, dosage regimen, dosing cycle, sampling interval, plasma half-life, washout period, and protocol adherence. Nominal requirements for the method are linear kinetics and mean plasma concentrations estimated over time intervals beginning and ending in the log-linear region."} {"id": "PMID:1271249", "title": "Correlation of phase inversion temperature with kinetics of globule coalescence for emulsions stabilized by a polyoxyethylene alkyl ether.", "content": "The phase inversion temperatures, globule coalescence rates, and long-term stability of oil-in-water emulsions stabilized by polyoxyethylene 4 cetyl ether were measured. Addition of sodium chloride to the aqueous phase depressed the phase inversion temperatures of the emulsions and the cloud point of the surfactant. Linear correlations were obtained between phase inversion temperature and cloud point and also between phase inversion temperature and the logarithm of the globule coalescence rate at constant temperature. This latter finding is consistent with a theory of emulsion type based upon the kinetics of coalescence. The programmed viscometric technique of determining inversion revealed the presence of a liquid crystalline phase below 35 degrees, which contributes significantly to emulsion stability.", "contents": "Correlation of phase inversion temperature with kinetics of globule coalescence for emulsions stabilized by a polyoxyethylene alkyl ether. The phase inversion temperatures, globule coalescence rates, and long-term stability of oil-in-water emulsions stabilized by polyoxyethylene 4 cetyl ether were measured. Addition of sodium chloride to the aqueous phase depressed the phase inversion temperatures of the emulsions and the cloud point of the surfactant. Linear correlations were obtained between phase inversion temperature and cloud point and also between phase inversion temperature and the logarithm of the globule coalescence rate at constant temperature. This latter finding is consistent with a theory of emulsion type based upon the kinetics of coalescence. The programmed viscometric technique of determining inversion revealed the presence of a liquid crystalline phase below 35 degrees, which contributes significantly to emulsion stability."} {"id": "PMID:1271250", "title": "Effect of absorbents on water vapor transmission of free and applied polymer films.", "content": "The influence of different types of absorbents on moisture transmission through free (cast films) and applied (coated tablets) polymer films was investigated. In free film studies, lubricated granulations were considered to be the absorbent. The compressed tablet was considered to be the absorbent in applied film studies. The results suggested that, using the same film formulation and film thickness in all cases, the polymer film reduced moisture absorption to the same degree, independent of the absorbent used, suggesting a constant moisture permeation. The results of the free film studies also simulated those of the applied films, allowing the correlation of the data.", "contents": "Effect of absorbents on water vapor transmission of free and applied polymer films. The influence of different types of absorbents on moisture transmission through free (cast films) and applied (coated tablets) polymer films was investigated. In free film studies, lubricated granulations were considered to be the absorbent. The compressed tablet was considered to be the absorbent in applied film studies. The results suggested that, using the same film formulation and film thickness in all cases, the polymer film reduced moisture absorption to the same degree, independent of the absorbent used, suggesting a constant moisture permeation. The results of the free film studies also simulated those of the applied films, allowing the correlation of the data."} {"id": "PMID:1271251", "title": "Conversion of biguanides into substituted s-triazines assayable by GC or mass fragmentography.", "content": "Substituted s-triazines were prepared by the treatment of biguanides with various organic acid anhydrides. This reaction permits the ready conversion of the hypoglycemic drugs phenformin, buformin, and metformin and of other analogous biguanides into compounds suitable for GC and mass fragmentographic determination with a high degree of sensitivity. Mass spectral data and Kov\u00e1ts retention indexes are presented for all s-triazines prepared for this study.", "contents": "Conversion of biguanides into substituted s-triazines assayable by GC or mass fragmentography. Substituted s-triazines were prepared by the treatment of biguanides with various organic acid anhydrides. This reaction permits the ready conversion of the hypoglycemic drugs phenformin, buformin, and metformin and of other analogous biguanides into compounds suitable for GC and mass fragmentographic determination with a high degree of sensitivity. Mass spectral data and Kov\u00e1ts retention indexes are presented for all s-triazines prepared for this study."} {"id": "PMID:1271252", "title": "Correlation between dissolution characteristics and absorption of methaqualone from solid dosage forms.", "content": "A methaqualone tablet in two strengths, 150 and 300 mg, was developed. The dissolution rate of an experimental formulation in pH 7.0 phosphate buffer, measured by the resin flask method, was shown to correlate with bioavailability in humans. The dissolution rate criterion was used to develop the final tablet formulation. Bioavailability of this formulation in two strengths was compared with a commercial capsule formulation and a slowly dissolving tablet formulation. Correlation between dissolution rate and bioavailability was shown in freshly prepared methaqualone tablet formulations. Bioavailability of tablets under accelerated stability testing conditions remained unaltered, whereas the dissolution rates in pH 7 phosphate buffer decreased, using the resin flask method. A rotating-flask method was developed, and dissolution in 0.1 N HCl at 2 rpm correlated with the bioavailability of both new and aged tablet formulations.", "contents": "Correlation between dissolution characteristics and absorption of methaqualone from solid dosage forms. A methaqualone tablet in two strengths, 150 and 300 mg, was developed. The dissolution rate of an experimental formulation in pH 7.0 phosphate buffer, measured by the resin flask method, was shown to correlate with bioavailability in humans. The dissolution rate criterion was used to develop the final tablet formulation. Bioavailability of this formulation in two strengths was compared with a commercial capsule formulation and a slowly dissolving tablet formulation. Correlation between dissolution rate and bioavailability was shown in freshly prepared methaqualone tablet formulations. Bioavailability of tablets under accelerated stability testing conditions remained unaltered, whereas the dissolution rates in pH 7 phosphate buffer decreased, using the resin flask method. A rotating-flask method was developed, and dissolution in 0.1 N HCl at 2 rpm correlated with the bioavailability of both new and aged tablet formulations."} {"id": "PMID:1271253", "title": "Hypocholesterolemic agents III: inhibition of beta-hydroxy-beta-methylglutaryl coenzyme A reductase by half acid esters of 1-(4-biphenylyl)pentanol.", "content": "A series of half acid esters of 1-(4-biphenylyl)pentanol was synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. The number of methylenes separating the carboxyl and ester groups was varied from zero to six. A minimum of one methylene was required for reasonable activity. Further separation of the carboxyl and ester groups produced small changes in activity. Investigation of several isomeric (cis and trans) half acid esters indicated that activity was independent of configuration. Modification of the acid portion of the glutarate analog by incorporating a 3-hydroxyl group increased activity sixfold.", "contents": "Hypocholesterolemic agents III: inhibition of beta-hydroxy-beta-methylglutaryl coenzyme A reductase by half acid esters of 1-(4-biphenylyl)pentanol. A series of half acid esters of 1-(4-biphenylyl)pentanol was synthesized and assayed for inhibition of rat liver beta-hydroxy-beta-methylglutaryl coenzyme A reductase. The number of methylenes separating the carboxyl and ester groups was varied from zero to six. A minimum of one methylene was required for reasonable activity. Further separation of the carboxyl and ester groups produced small changes in activity. Investigation of several isomeric (cis and trans) half acid esters indicated that activity was independent of configuration. Modification of the acid portion of the glutarate analog by incorporating a 3-hydroxyl group increased activity sixfold."} {"id": "PMID:1271254", "title": "N-halo derivatives III: stabilization of nitrogen-chlorine bond in N-chloroamino acid derivatives.", "content": "The chlorination of alpha-amino acids and their related derivatives was investigated. A kinetic study of the stability of these N-chlorinated products led to an elucidation of the factors that significantly influence the stability and reactivity of the nitrogen-chlorine bond in these N-chloramines. From the kinetic investigations, a series of low chlorine potential, soft antimicrobial N-chloramines was developed based on derivatives of alpha-aminoisobutyric acid and related compounds.", "contents": "N-halo derivatives III: stabilization of nitrogen-chlorine bond in N-chloroamino acid derivatives. The chlorination of alpha-amino acids and their related derivatives was investigated. A kinetic study of the stability of these N-chlorinated products led to an elucidation of the factors that significantly influence the stability and reactivity of the nitrogen-chlorine bond in these N-chloramines. From the kinetic investigations, a series of low chlorine potential, soft antimicrobial N-chloramines was developed based on derivatives of alpha-aminoisobutyric acid and related compounds."} {"id": "PMID:1271255", "title": "Isolation of flindersiamine, isoflindersiamine, and a new alkaloid, heliparvifoline, from Helietta parvifolia (Rutaceae).", "content": "A phytochemical investigation of the leaves and twigs of Helietta parvifolia (Rutaceae) resulted in the isolation of heliparvifoline, a new furoquinoline alkaloid, in addition to the known bases flindersiamine and isoflindersiamine.", "contents": "Isolation of flindersiamine, isoflindersiamine, and a new alkaloid, heliparvifoline, from Helietta parvifolia (Rutaceae). A phytochemical investigation of the leaves and twigs of Helietta parvifolia (Rutaceae) resulted in the isolation of heliparvifoline, a new furoquinoline alkaloid, in addition to the known bases flindersiamine and isoflindersiamine."} {"id": "PMID:1271256", "title": "Improved transport apparatus for examining diffusion of drugs across isolated tissues and synthetic membranes.", "content": "A three-compartment diffusion apparatus that can accommodate synthetic as well as small isolated biological membranes such as rat intestine was developed and tested. The diffusion of drug from two outer donor cells into a central recipient cell allows for more membrane surface exposure and greater sensitivity in assaying as compared with previously published techniques. Reproducibility values for the synthetic membrane were equivalent to those obtained in more elaborate designs, while the reproducibility for biological membranes compared favorably with everted gut preparations and a similar diffusion apparatus. The clearance, per square centimeter of membrane, of salicylamide at pH 7.4 and 37 degrees was 0.288 ml/hr/cm2, which agreed with previous literature reports of different techniques. Although the diffusion through a synthetic membrane was more rapid, introduction of a nonionic surfactant enhanced the biological perfusion rate while having no significant effect on the synthetic barrier. The enhancement of the diffusion rate effected by 0.1 and 0.01% (w/v) surfactant was about twofold, rapid in onset, and not progressive, giving clearance values per square centimeter of 0.606 and 0.537 ml/hr/cm2, respectively.", "contents": "Improved transport apparatus for examining diffusion of drugs across isolated tissues and synthetic membranes. A three-compartment diffusion apparatus that can accommodate synthetic as well as small isolated biological membranes such as rat intestine was developed and tested. The diffusion of drug from two outer donor cells into a central recipient cell allows for more membrane surface exposure and greater sensitivity in assaying as compared with previously published techniques. Reproducibility values for the synthetic membrane were equivalent to those obtained in more elaborate designs, while the reproducibility for biological membranes compared favorably with everted gut preparations and a similar diffusion apparatus. The clearance, per square centimeter of membrane, of salicylamide at pH 7.4 and 37 degrees was 0.288 ml/hr/cm2, which agreed with previous literature reports of different techniques. Although the diffusion through a synthetic membrane was more rapid, introduction of a nonionic surfactant enhanced the biological perfusion rate while having no significant effect on the synthetic barrier. The enhancement of the diffusion rate effected by 0.1 and 0.01% (w/v) surfactant was about twofold, rapid in onset, and not progressive, giving clearance values per square centimeter of 0.606 and 0.537 ml/hr/cm2, respectively."} {"id": "PMID:1271257", "title": "Development of an aerosol dosage form containing insulin.", "content": "An aerosol dosage form containing insulin was developed by suspending insulin zinc crystals in fluorocarbon propellant and using oleyl alcohol to improve the insulin suspension and to prevent valve clogging. A metered valve was used to control the amount of insulin delivered per actuation. The dose dispensed, sedimentation rate, and particle-size distribution of the aerosol formulation were evaluated. The potency of the insulin delivered from the aerosol containers stored at various temperatures and time intervals was determined using a radioimmunoassay. Based upon preliminary stability data, which were treated kinetically, it was noted that insulin aerosols stored in a refrigerator at 7 degrees would have a predicted shelflife of approximately 19 years, whereas samples stored at 25 and 37 degrees would have shelflives of 11 and 2 months, respectively. Long-term stability studies are indicated to establish this conclusion. On the basis of this study, it was concluded that an insulin-containing aerosol dosage form can be formulated and that a suitable dose of insulin can be dispensed using commercially available metered dose valves. The actual dose of insulin dispensed would have to be related to the degree of absorption of insulin one would normally expect when insulin is administered by the inhalation route.", "contents": "Development of an aerosol dosage form containing insulin. An aerosol dosage form containing insulin was developed by suspending insulin zinc crystals in fluorocarbon propellant and using oleyl alcohol to improve the insulin suspension and to prevent valve clogging. A metered valve was used to control the amount of insulin delivered per actuation. The dose dispensed, sedimentation rate, and particle-size distribution of the aerosol formulation were evaluated. The potency of the insulin delivered from the aerosol containers stored at various temperatures and time intervals was determined using a radioimmunoassay. Based upon preliminary stability data, which were treated kinetically, it was noted that insulin aerosols stored in a refrigerator at 7 degrees would have a predicted shelflife of approximately 19 years, whereas samples stored at 25 and 37 degrees would have shelflives of 11 and 2 months, respectively. Long-term stability studies are indicated to establish this conclusion. On the basis of this study, it was concluded that an insulin-containing aerosol dosage form can be formulated and that a suitable dose of insulin can be dispensed using commercially available metered dose valves. The actual dose of insulin dispensed would have to be related to the degree of absorption of insulin one would normally expect when insulin is administered by the inhalation route."} {"id": "PMID:1271258", "title": "Effect of thermal gelation on dissolution from coated tablets.", "content": "Tablets with a methylcellulose coating were found to exhibit lower dissolution profiles than those coated with a hydroxypropyl methylcellulose coating at 37 degrees, and the cause was investigated. The differences are attributed to thermal gelation of the methylcellulose at temperatures near 37 degrees, which creates a barrier to the dissolution process and essentially changes the dissolution mechanism. This mechanism is substantiated by the fact that at temperatures below the gel point and at increased agitation, the effect disappears. The retarded dissolution effect is not peculiar to the drug involved.", "contents": "Effect of thermal gelation on dissolution from coated tablets. Tablets with a methylcellulose coating were found to exhibit lower dissolution profiles than those coated with a hydroxypropyl methylcellulose coating at 37 degrees, and the cause was investigated. The differences are attributed to thermal gelation of the methylcellulose at temperatures near 37 degrees, which creates a barrier to the dissolution process and essentially changes the dissolution mechanism. This mechanism is substantiated by the fact that at temperatures below the gel point and at increased agitation, the effect disappears. The retarded dissolution effect is not peculiar to the drug involved."} {"id": "PMID:1271259", "title": "GLC determination of plasma levels of intact chlorpropamide or tolbutamide.", "content": "A GLC procedure was developed for the quantitative estimation of intact chlorpropamide and tolbutamide concentrations in plasma; the drugs are used as mutual internal standards. After extraction of plasma containing the drug and internal standard with toluene, the dried residue is treated with ethereal diazomethane to form the methyl derivatives of tolbutamide and chlorpropamide. Aliquots of the ethereal solution are injected into a gas chromatograph equipped with a glass-lined injection port and glass column packed with a phenyl methyl silicone fluid (OV-25) on Chromosorb W, which facilitates the intact determination of the methyl derivatives of the drugs. The response to the flame-ionization detector was linear over a range of 0.20-25 mug/ml, with a 0.05-mug/ml limit of detectability for both drugs. The method compares favorably with a recently developed high-pressure liquid chromatographic procedure and is adequate for following blood level profiles of single doses of chlorpropamide (125 mg) and tolbutamide (250 mg). Mass spectral evidence showing that intact sulfonylureas are measured is presented.", "contents": "GLC determination of plasma levels of intact chlorpropamide or tolbutamide. A GLC procedure was developed for the quantitative estimation of intact chlorpropamide and tolbutamide concentrations in plasma; the drugs are used as mutual internal standards. After extraction of plasma containing the drug and internal standard with toluene, the dried residue is treated with ethereal diazomethane to form the methyl derivatives of tolbutamide and chlorpropamide. Aliquots of the ethereal solution are injected into a gas chromatograph equipped with a glass-lined injection port and glass column packed with a phenyl methyl silicone fluid (OV-25) on Chromosorb W, which facilitates the intact determination of the methyl derivatives of the drugs. The response to the flame-ionization detector was linear over a range of 0.20-25 mug/ml, with a 0.05-mug/ml limit of detectability for both drugs. The method compares favorably with a recently developed high-pressure liquid chromatographic procedure and is adequate for following blood level profiles of single doses of chlorpropamide (125 mg) and tolbutamide (250 mg). Mass spectral evidence showing that intact sulfonylureas are measured is presented."} {"id": "PMID:1271260", "title": "Mechanism of action of retinyl compounds on wound healing IV: effect of desmethylretinoic acid and its vinylogs on granuloma formation.", "content": "The effect of side-chain length of desmethylretinoic acid on granuloma formation induced by implantation of cotton pellets was studied. As in the homologous series of retinoic acid studies, compounds with side chains shorter than retinoic acid were not active while compounds with side chains as long or longer than retinoic acid were active. The compound with a chain two carbons longer than retinoic acid was the most active. The hydroxyproline and hexosamine contents of the granuloma were analyzed. The mechanisms of action of these active compounds on wound healing are discussed.", "contents": "Mechanism of action of retinyl compounds on wound healing IV: effect of desmethylretinoic acid and its vinylogs on granuloma formation. The effect of side-chain length of desmethylretinoic acid on granuloma formation induced by implantation of cotton pellets was studied. As in the homologous series of retinoic acid studies, compounds with side chains shorter than retinoic acid were not active while compounds with side chains as long or longer than retinoic acid were active. The compound with a chain two carbons longer than retinoic acid was the most active. The hydroxyproline and hexosamine contents of the granuloma were analyzed. The mechanisms of action of these active compounds on wound healing are discussed."} {"id": "PMID:1271261", "title": "Solvent-dependent conformational system in hydroxyureas detected by NMR spectroscopy.", "content": "The proton magnetic resonance spectra of the antileukemia agent hydroxyurea and substituted hydroxyureas in several solvents were recorded and correlated with structural features. Solvent-dependent differences in conformational preferences due to effects on internal hydrogen bonding, a temperature-dependent conformational feature, anthe exchangeability of protons with deuterium oxide and acetone-d6 were observed. The conformational features consistent with the spectral data are discussed.", "contents": "Solvent-dependent conformational system in hydroxyureas detected by NMR spectroscopy. The proton magnetic resonance spectra of the antileukemia agent hydroxyurea and substituted hydroxyureas in several solvents were recorded and correlated with structural features. Solvent-dependent differences in conformational preferences due to effects on internal hydrogen bonding, a temperature-dependent conformational feature, anthe exchangeability of protons with deuterium oxide and acetone-d6 were observed. The conformational features consistent with the spectral data are discussed."} {"id": "PMID:1271262", "title": "Rapid determination of dimethyl polysiloxane by proton magnetic resonance spectroscopy.", "content": "A new procedure is described for the quantitative extraction and determination of dimethyl polysiloxane by 1H-NMR spectroscopy, using tetrachloroethylene as the solvent and dioxane as the internal reference.", "contents": "Rapid determination of dimethyl polysiloxane by proton magnetic resonance spectroscopy. A new procedure is described for the quantitative extraction and determination of dimethyl polysiloxane by 1H-NMR spectroscopy, using tetrachloroethylene as the solvent and dioxane as the internal reference."} {"id": "PMID:1271263", "title": "NMR determination of enantiomers of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo(3,2-b)(1,3)benzoxazin-9-one using chiral shift reagent, tris(3-(heptafluorobutyryl)-d-camphorato)europium(III).", "content": "A simple NMR method was developed for the determination of the enantiomers of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo[3,2-b][1,3]benzoxazin-9-one. Chiral shift reagent, tris[3-(heptafluoroburyryl)-d-camphorato]europium(III), causes the doublet assigned to the protons of the 2-methyl group, which normally appears at about 1.5 ppm, to split into two pairs of doublets and to shift downfield to about 2.0-3.5 ppm. The downfield pair of doublets represents the two enantiomers present in one racemate, designated as the beta-form, while the upfield pair represents the enantiomers of the racemate designated as the alpha-form. From the integration of the area under the doublets, the relative concentration of all four enantiomers was determined.", "contents": "NMR determination of enantiomers of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo(3,2-b)(1,3)benzoxazin-9-one using chiral shift reagent, tris(3-(heptafluorobutyryl)-d-camphorato)europium(III). A simple NMR method was developed for the determination of the enantiomers of 7-chloro-3,3a-dihydro-2-methyl-2H,9H-isoxazolo[3,2-b][1,3]benzoxazin-9-one. Chiral shift reagent, tris[3-(heptafluoroburyryl)-d-camphorato]europium(III), causes the doublet assigned to the protons of the 2-methyl group, which normally appears at about 1.5 ppm, to split into two pairs of doublets and to shift downfield to about 2.0-3.5 ppm. The downfield pair of doublets represents the two enantiomers present in one racemate, designated as the beta-form, while the upfield pair represents the enantiomers of the racemate designated as the alpha-form. From the integration of the area under the doublets, the relative concentration of all four enantiomers was determined."} {"id": "PMID:1271264", "title": "Comparison of protective effects of ethylestrenol, norbolethone, and spironolactone against lethality from acute doses of parathion and paraoxon in female rats.", "content": "Protection against the toxicity of parathion (increased LD50) was provided by preadministered ethylestrenol and, to a lesser extent, by norbolethone and spironlactone. Ethylestrenol and norbolethone also offered protection against paraoxon toxicity. With ethylestrenol and spironolactone, the protection against parathion lethality was greater than that against paraoxon lethality.", "contents": "Comparison of protective effects of ethylestrenol, norbolethone, and spironolactone against lethality from acute doses of parathion and paraoxon in female rats. Protection against the toxicity of parathion (increased LD50) was provided by preadministered ethylestrenol and, to a lesser extent, by norbolethone and spironlactone. Ethylestrenol and norbolethone also offered protection against paraoxon toxicity. With ethylestrenol and spironolactone, the protection against parathion lethality was greater than that against paraoxon lethality."} {"id": "PMID:1271265", "title": "Determination of nitrofurantoin in urine by reduction at rotating platinum electrode.", "content": "The application of the reduction of nitrofurantoin at the rotating platinum electrode to the determination of the drug in the urine of clinical patients was evaluated and compared to a commonly used colorimetric method. The new electrochemical method was found to be faster and more efficient with precision and accuracy comparable to those of the colorimetric method.", "contents": "Determination of nitrofurantoin in urine by reduction at rotating platinum electrode. The application of the reduction of nitrofurantoin at the rotating platinum electrode to the determination of the drug in the urine of clinical patients was evaluated and compared to a commonly used colorimetric method. The new electrochemical method was found to be faster and more efficient with precision and accuracy comparable to those of the colorimetric method."} {"id": "PMID:1271266", "title": "Simple transformation method for predicting plasma drug profiles from dissolution rates.", "content": "A transformation factor is described which related in vitro drug dissolution from a preparation to the corresponding in vivo plasma drug concentrations. This factor, derived from the dissolution profile and the corresponding in vivo plasma concentration of a single formulation, was used to predict plasma concentration profiles of similar formulations simply from dissolution data.", "contents": "Simple transformation method for predicting plasma drug profiles from dissolution rates. A transformation factor is described which related in vitro drug dissolution from a preparation to the corresponding in vivo plasma drug concentrations. This factor, derived from the dissolution profile and the corresponding in vivo plasma concentration of a single formulation, was used to predict plasma concentration profiles of similar formulations simply from dissolution data."} {"id": "PMID:1271267", "title": "Protein-binding polyhedral boranes II: DL-S-(10-dimethylsulfidooctahydrodecaborane)methionine.", "content": "An analog of methionine, DL-S-(10-dimethylsulfidooctahydrodecaborane)methionine, was synthesized from fully protected homoserine. A protected dipeptide with glycine is described.", "contents": "Protein-binding polyhedral boranes II: DL-S-(10-dimethylsulfidooctahydrodecaborane)methionine. An analog of methionine, DL-S-(10-dimethylsulfidooctahydrodecaborane)methionine, was synthesized from fully protected homoserine. A protected dipeptide with glycine is described."} {"id": "PMID:1271268", "title": "High-speed liquid chromatographic determination of procaine in pharmaceuticals.", "content": "The operating conditions for a quantitative method of determining procaine in pharmaceutical preparations by high-speed liquid chromatography are described. The presence of decomposition products and the possible interference of other ingredients usually present in pharmaceutical preparations were found to have no effect. The method, because of its simplicity, is highly suited for routine analysis of pharmaceutical preparations containing procaine.", "contents": "High-speed liquid chromatographic determination of procaine in pharmaceuticals. The operating conditions for a quantitative method of determining procaine in pharmaceutical preparations by high-speed liquid chromatography are described. The presence of decomposition products and the possible interference of other ingredients usually present in pharmaceutical preparations were found to have no effect. The method, because of its simplicity, is highly suited for routine analysis of pharmaceutical preparations containing procaine."} {"id": "PMID:1271269", "title": "GLC analysis of lidocaine in blood using an alkaline flame-ionization detector.", "content": "A method was developed for the quantitative GLC determination of lidocaine and its major metabolite monoethylglycinexylidide. By using the specificity of the alkaline flame-ionization detector, this simple analytical procedure is extremely sensitive, rapid, and easily performed.", "contents": "GLC analysis of lidocaine in blood using an alkaline flame-ionization detector. A method was developed for the quantitative GLC determination of lidocaine and its major metabolite monoethylglycinexylidide. By using the specificity of the alkaline flame-ionization detector, this simple analytical procedure is extremely sensitive, rapid, and easily performed."} {"id": "PMID:1271270", "title": "Onset of enzyme induction with pregnenolone-16alpha-carbonitrile in male and female rats.", "content": "Male and female rats treated with a single 20-mg/kg ip dose of pregnenolone-16alpha-carbonitrile (PCN) produced parallel increases in hepatic cytochrome P-450 and aniline hydroxylase activity. However, the onset of increase in aniline hydroxylase activity and cytochrome P-450 content was slower in male than female animals. The maximal levels achieved in male rats were 89% of the values observed in the female animals. Furthermore, the hepatic aniline hydroxylase activity and P-450 content declined more rapidly in male than in female rats.", "contents": "Onset of enzyme induction with pregnenolone-16alpha-carbonitrile in male and female rats. Male and female rats treated with a single 20-mg/kg ip dose of pregnenolone-16alpha-carbonitrile (PCN) produced parallel increases in hepatic cytochrome P-450 and aniline hydroxylase activity. However, the onset of increase in aniline hydroxylase activity and cytochrome P-450 content was slower in male than female animals. The maximal levels achieved in male rats were 89% of the values observed in the female animals. Furthermore, the hepatic aniline hydroxylase activity and P-450 content declined more rapidly in male than in female rats."} {"id": "PMID:1271271", "title": "Synthesis and biological evaluation of 1-(4-hydroxy-2-oxo-2H-1-benzopyran-3-yl)pyridinium hydroxide inner salt derivatives.", "content": "Eight 1-(4-hydroxy-2-oxo-2H-1-benzopyran-3-yl)pyridinium hydroxide inner salts were synthesized, and the antibacterial, antifungal, anticoccidial, and anthelmintic activities were determined against different microorganisms, the protozoan Eimeria tenella, and trichostrongyle nematodes. All were noninhibitory to Gram-negative bacteria and the parasites. The pyridine, 4-benzylpyridine, and 2-isoquinoline inner salt derivatives controlled only Rhizoctonia solani of the four genera of fungi challenged.", "contents": "Synthesis and biological evaluation of 1-(4-hydroxy-2-oxo-2H-1-benzopyran-3-yl)pyridinium hydroxide inner salt derivatives. Eight 1-(4-hydroxy-2-oxo-2H-1-benzopyran-3-yl)pyridinium hydroxide inner salts were synthesized, and the antibacterial, antifungal, anticoccidial, and anthelmintic activities were determined against different microorganisms, the protozoan Eimeria tenella, and trichostrongyle nematodes. All were noninhibitory to Gram-negative bacteria and the parasites. The pyridine, 4-benzylpyridine, and 2-isoquinoline inner salt derivatives controlled only Rhizoctonia solani of the four genera of fungi challenged."} {"id": "PMID:1271274", "title": "New compounds: synthesis of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride.", "content": "Reaction of 2,3,4,5,6-pentafluorobenzyl bromide with N-hydroxyphthalimide produced N-(2,3,4,5,6-pentafluorobenzyloxy)phthalimide which, after hydrazinolysis and treatment with hydrogen chloride, yielded O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride. The latter compound was used to derivatize keto steroids for their analysis by electron-capture GLC.", "contents": "New compounds: synthesis of O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride. Reaction of 2,3,4,5,6-pentafluorobenzyl bromide with N-hydroxyphthalimide produced N-(2,3,4,5,6-pentafluorobenzyloxy)phthalimide which, after hydrazinolysis and treatment with hydrogen chloride, yielded O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine hydrochloride. The latter compound was used to derivatize keto steroids for their analysis by electron-capture GLC."} {"id": "PMID:1271275", "title": "New compounds: derivatives of methyl 2-aminoacetyl-4,5-dimethoxyphenylacetate.", "content": "Methyl 2-bromoacetyl-4,5-dimethoxyphenylacetate was prepared by reacting cupric bromide with methyl 2-acetyl-4,5-dimethoxyphenylacetate. Aminoacetyl derivatives formed on condensation of substituted p-aminobenzoic esters with the bromoacetyl derivative. Some prepared compounds were tested for local anesthetic and anti-inflammatory activities.", "contents": "New compounds: derivatives of methyl 2-aminoacetyl-4,5-dimethoxyphenylacetate. Methyl 2-bromoacetyl-4,5-dimethoxyphenylacetate was prepared by reacting cupric bromide with methyl 2-acetyl-4,5-dimethoxyphenylacetate. Aminoacetyl derivatives formed on condensation of substituted p-aminobenzoic esters with the bromoacetyl derivative. Some prepared compounds were tested for local anesthetic and anti-inflammatory activities."} {"id": "PMID:1271278", "title": "Biodisposition of ketamine in the rat: self-induction of metabolism.", "content": "Four pharmacologic actions of intravenous ketamine (30 mg/kg) were studied in the rat. To elucidate the mechanism(s) terminating the pharmacologic effects, animals were pretreated with ketamine and agents anticipated to modify hepatic microsomal metabolism, including phenobarbital and SKF 525A. SKF 525A pretreatment markedly prolonged ataxia, analgesia and agitation, in addition to significantly elevating brain and plasma ketamine levels subsequent to the initial 10 minutes following injection; thus hepatic metabolism appeared to play a prominent role in the termination of the posthypnotic effects of the drug. While significantly shortening the durations of the three posthypnotic events, phenobarbital and ketamine pretreatments also lowered the brain and plasma levels of ketamine. With all pretreatments, brain ketamine levels were almost identical at the cessation of hypnosis (25 mug/g of tissue) and ataxia (8-10 mug/g of tissue). No pretreatment altered either the duration of loss of righting reflex (hypnosis) or brain and plasma ketamine levels during the initial 10 minutes after injection. Approximately 70% of the injected drug was recovered from four tissues, skeletal muscle, gut, skin and liver, at 10 minutes after injection; thus redistribution from brain to other tissues appeared to play a major role in the cessation of hypnosis. Ketamine pretreatment caused a 2-fold increase in the rate of its in vitro hepatic microsomal metabolism. Brain and plasma ketamine levels 30 minutes after injection were nearly identical in rats pretreated with ketamine and phenobarbital, although phenobarbital pretreatment resulted in a 4-fold increase in in vitro ketamine hepatic metabolism.", "contents": "Biodisposition of ketamine in the rat: self-induction of metabolism. Four pharmacologic actions of intravenous ketamine (30 mg/kg) were studied in the rat. To elucidate the mechanism(s) terminating the pharmacologic effects, animals were pretreated with ketamine and agents anticipated to modify hepatic microsomal metabolism, including phenobarbital and SKF 525A. SKF 525A pretreatment markedly prolonged ataxia, analgesia and agitation, in addition to significantly elevating brain and plasma ketamine levels subsequent to the initial 10 minutes following injection; thus hepatic metabolism appeared to play a prominent role in the termination of the posthypnotic effects of the drug. While significantly shortening the durations of the three posthypnotic events, phenobarbital and ketamine pretreatments also lowered the brain and plasma levels of ketamine. With all pretreatments, brain ketamine levels were almost identical at the cessation of hypnosis (25 mug/g of tissue) and ataxia (8-10 mug/g of tissue). No pretreatment altered either the duration of loss of righting reflex (hypnosis) or brain and plasma ketamine levels during the initial 10 minutes after injection. Approximately 70% of the injected drug was recovered from four tissues, skeletal muscle, gut, skin and liver, at 10 minutes after injection; thus redistribution from brain to other tissues appeared to play a major role in the cessation of hypnosis. Ketamine pretreatment caused a 2-fold increase in the rate of its in vitro hepatic microsomal metabolism. Brain and plasma ketamine levels 30 minutes after injection were nearly identical in rats pretreated with ketamine and phenobarbital, although phenobarbital pretreatment resulted in a 4-fold increase in in vitro ketamine hepatic metabolism."} {"id": "PMID:1271279", "title": "Specificity of release of biogenic amines from isolated rat brain tissue as a function of the meta substituent of N-ethylamphetamine derivatives.", "content": "The actions of several meta-substituted N-ethylamphetamines on the release, uptake and catabolism of biogenic amines were investigated in vitro in two regions of rat brain. Each of the compounds released 3H-norepinephrine from chopped cerebral cortex, and 3H-dopamine and 3H-5-hydroxytryptamine from chopped corpus striatum. Stepwise multiple linear regression analyses indicated that the potencies (EC50 values) with which the compounds released 3H-norepinephrine were inversely related (r = 0.94) to the size of the meta substituent. Addition of substituent lipophilic or electronic effects to the regression equation did not greatly improve the correlation. However, the maximal release of 3H-norepinephrine produced by these compounds was directly related only to substituent lipophilic effects (r = 0.95). The potencies and maxima with which the compounds released 3H-dopamine or 3H-5-hydroxytryptamine and the potencies with which the compounds inhibited the uptake of the 3H-amines were not correlated with substituent size, lipophilicity or electronegativity. Variations in meta substituent also altered the degree to which the release 3H-amines were metabolized by monoamine oxidase. Multiple linear regression analyses indicated that for each of the 3H-amines, the maximal percent increase in 3H-deaminated metabolites produced by the drugs was directly correlated only with substituent size (r = 0.85, 0.89 and 0.95 for 3H-norepinephrine, 3H-dopamine and 3H-5-hydroxytryptamine, respectively). Comparisons among the potencies with which compounds released the various 3H-amines indicated that, in general, as substituent size increased, the compounds became relatively less potent in releasing 3H-catecholamines and relatively more potent in releasing 3H-5-hydroxytryptamine. Thus, these studies indicate that variations in the meta substituent group of N-ethylamphetamine derivatives determine the affinity of the derivatives for norepinephrine nerve endings and the relative affinities of the derivatives for norepinephrine, dopamine and 5-hydroxytryptamine nerve endings.", "contents": "Specificity of release of biogenic amines from isolated rat brain tissue as a function of the meta substituent of N-ethylamphetamine derivatives. The actions of several meta-substituted N-ethylamphetamines on the release, uptake and catabolism of biogenic amines were investigated in vitro in two regions of rat brain. Each of the compounds released 3H-norepinephrine from chopped cerebral cortex, and 3H-dopamine and 3H-5-hydroxytryptamine from chopped corpus striatum. Stepwise multiple linear regression analyses indicated that the potencies (EC50 values) with which the compounds released 3H-norepinephrine were inversely related (r = 0.94) to the size of the meta substituent. Addition of substituent lipophilic or electronic effects to the regression equation did not greatly improve the correlation. However, the maximal release of 3H-norepinephrine produced by these compounds was directly related only to substituent lipophilic effects (r = 0.95). The potencies and maxima with which the compounds released 3H-dopamine or 3H-5-hydroxytryptamine and the potencies with which the compounds inhibited the uptake of the 3H-amines were not correlated with substituent size, lipophilicity or electronegativity. Variations in meta substituent also altered the degree to which the release 3H-amines were metabolized by monoamine oxidase. Multiple linear regression analyses indicated that for each of the 3H-amines, the maximal percent increase in 3H-deaminated metabolites produced by the drugs was directly correlated only with substituent size (r = 0.85, 0.89 and 0.95 for 3H-norepinephrine, 3H-dopamine and 3H-5-hydroxytryptamine, respectively). Comparisons among the potencies with which compounds released the various 3H-amines indicated that, in general, as substituent size increased, the compounds became relatively less potent in releasing 3H-catecholamines and relatively more potent in releasing 3H-5-hydroxytryptamine. Thus, these studies indicate that variations in the meta substituent group of N-ethylamphetamine derivatives determine the affinity of the derivatives for norepinephrine nerve endings and the relative affinities of the derivatives for norepinephrine, dopamine and 5-hydroxytryptamine nerve endings."} {"id": "PMID:1271280", "title": "Comparative actions of monomethoxyamphetamines on the release and uptake of biogenic amines in brain tissue.", "content": "para-Methoxyamphetamine (PMA), a known hallucinogen, is the most potent compound among methoxyamphetamines in disrupting behavior in rats. PMA, unlike d-amphetamine (A), did not induce stereotyped behavior and was less effective than A in stimulation of locomotor d-amphetamine-like effects, but ortho-methoxyamphetamine (OMA) was devoid of any locomotor stimulation. To investigate the reasons for the different behavioral effects caused by PMA, meta-methoxyamphetamine (MMA), OMA and A, a comparison was made among these drugs on the release and uptake of 3H-5-hydroxytryptamine (3H-5-HT), 3H-norepinephrine (3H-NE) and 3H-dopamine (3H-DA) in tissue slices of cerebral cortex and corpus striatum of rat brain. The potencies for the increased release of 3H-5-HT were found to be PMA greater than MMA greater than or equal to A greater than OMA in cerebral cortex of 3H-NE in cortex, A greater than or equal to PMA = MMA greater than OMA, and of 3H-DA in corpus striatum, A greater than MMA greater than PMA greater than or equal to OMA. The potencies for inhibiting the uptake of 3H-5-HT in cerebral cortex and corpus striatum were found to be PMA greater than MMA greater than A greater than OMA and of 3H-NE in cortex A greater than PMA greater than or equal to MMA greater than OMA, and 3H-DA in corpus striatum A greater than MMA greater than PMA greater than OMA. d-PMA is equipotent to l-PMA in increasing the release of 3H-5-HT but is more potent than l-PMA in blocking the uptake of 3H-5-HT. The high potency of PMA on increasing the release and inhibiting the uptake of 5-HT suggests than 5-HT may be involved in the production of hallucinogenic effects of PMA.", "contents": "Comparative actions of monomethoxyamphetamines on the release and uptake of biogenic amines in brain tissue. para-Methoxyamphetamine (PMA), a known hallucinogen, is the most potent compound among methoxyamphetamines in disrupting behavior in rats. PMA, unlike d-amphetamine (A), did not induce stereotyped behavior and was less effective than A in stimulation of locomotor d-amphetamine-like effects, but ortho-methoxyamphetamine (OMA) was devoid of any locomotor stimulation. To investigate the reasons for the different behavioral effects caused by PMA, meta-methoxyamphetamine (MMA), OMA and A, a comparison was made among these drugs on the release and uptake of 3H-5-hydroxytryptamine (3H-5-HT), 3H-norepinephrine (3H-NE) and 3H-dopamine (3H-DA) in tissue slices of cerebral cortex and corpus striatum of rat brain. The potencies for the increased release of 3H-5-HT were found to be PMA greater than MMA greater than or equal to A greater than OMA in cerebral cortex of 3H-NE in cortex, A greater than or equal to PMA = MMA greater than OMA, and of 3H-DA in corpus striatum, A greater than MMA greater than PMA greater than or equal to OMA. The potencies for inhibiting the uptake of 3H-5-HT in cerebral cortex and corpus striatum were found to be PMA greater than MMA greater than A greater than OMA and of 3H-NE in cortex A greater than PMA greater than or equal to MMA greater than OMA, and 3H-DA in corpus striatum A greater than MMA greater than PMA greater than OMA. d-PMA is equipotent to l-PMA in increasing the release of 3H-5-HT but is more potent than l-PMA in blocking the uptake of 3H-5-HT. The high potency of PMA on increasing the release and inhibiting the uptake of 5-HT suggests than 5-HT may be involved in the production of hallucinogenic effects of PMA."} {"id": "PMID:1271281", "title": "Effects of prenatal reserpine administration on development of the rat adrenal medulla and central nervous system.", "content": "Reserpine (1 mg/kg s.c.) was administered to pregnant rats at different periods of gestation. Rats born to mothers who received reserpine on days 6, 5 and 4 or 4, 3 and 2 before delivery showed early postnatal adrenal catecholamine depletion, an effect which can be attributed to a direct action of the drug; however, at no time was induction of tyrosine hydroxylase or dopamine beta-hydroxylase observed. Administration of reserpine on days 9, 8 and 7 before delivery did not alter postnatal adrenal catecholamine levels in the offspring but produced permanent elevations in enzyme activities and vesicular amine uptake beginning at 10 days of age. Studies utilizing direct stimulation with nicotine indicated that the inherent responsiveness of the adrenal medulla itself was the same in control and reserpine-exposed pups. These data all suggest that sympathoadrenal tone has been permanently increased in the offspring of rats which have been exposed to reserpine early in gestation. In the brain, administration of reserpine on days 6, 5 and 4 before delivery resulted in a delay in early postnatal development of brain weight and synaptosomal uptake mechanisms, and at later stages subnormal tyrosine hydroxylase activities. When reserpine was given on days 9, 8 and 7 before delivery, only the deficiency in tyrosine hydroxylase was seen. These studies indicate that long-lasting changes in both peripheral and central nervous system catecholamine disposition can be produced by prenatal reserpine administration.", "contents": "Effects of prenatal reserpine administration on development of the rat adrenal medulla and central nervous system. Reserpine (1 mg/kg s.c.) was administered to pregnant rats at different periods of gestation. Rats born to mothers who received reserpine on days 6, 5 and 4 or 4, 3 and 2 before delivery showed early postnatal adrenal catecholamine depletion, an effect which can be attributed to a direct action of the drug; however, at no time was induction of tyrosine hydroxylase or dopamine beta-hydroxylase observed. Administration of reserpine on days 9, 8 and 7 before delivery did not alter postnatal adrenal catecholamine levels in the offspring but produced permanent elevations in enzyme activities and vesicular amine uptake beginning at 10 days of age. Studies utilizing direct stimulation with nicotine indicated that the inherent responsiveness of the adrenal medulla itself was the same in control and reserpine-exposed pups. These data all suggest that sympathoadrenal tone has been permanently increased in the offspring of rats which have been exposed to reserpine early in gestation. In the brain, administration of reserpine on days 6, 5 and 4 before delivery resulted in a delay in early postnatal development of brain weight and synaptosomal uptake mechanisms, and at later stages subnormal tyrosine hydroxylase activities. When reserpine was given on days 9, 8 and 7 before delivery, only the deficiency in tyrosine hydroxylase was seen. These studies indicate that long-lasting changes in both peripheral and central nervous system catecholamine disposition can be produced by prenatal reserpine administration."} {"id": "PMID:1271282", "title": "Effects of intermittent and repeated administration of d-amphetamine on restricted water intake in rats.", "content": "Eleven rats had access to water 2 hours daily and intake was measured every 20 minutes. When given intermittently, increasing doses of d-amphetamine (0.05-1.6 mg/rat) decreased total water intake and altered the within-session distribution of intake, with proportionately less intake occurring within early portions of the session after larger doses. Repeated administration of d-amphetamine (0.2, 0.8 or 1.6 mg/rat/day) completely attenuated the overall intake-decreasing effects of the drug; the time taken for recovery of total intake increased with increasing dose. Despite complete tolerance to its overall intake-decreasing effects, d-amphetamine produced persistent dose-related effects on the distribution of intake within sessions that were only partially attenuated with continued daily administration of the drug. Tolerance to the overall intake-decreasing effect of 1.6 mg was accompanied by parallel shifts toward larger doses in the dose-effect functions for total water intake and for the within-session distribution of intake. Redetermination of the dose-effect functions at several times after the repeated administration of 1.6 mg generally showed that tolerance of d-amphetamine was lost within 25 to 57 days after discontinuation of the drug.", "contents": "Effects of intermittent and repeated administration of d-amphetamine on restricted water intake in rats. Eleven rats had access to water 2 hours daily and intake was measured every 20 minutes. When given intermittently, increasing doses of d-amphetamine (0.05-1.6 mg/rat) decreased total water intake and altered the within-session distribution of intake, with proportionately less intake occurring within early portions of the session after larger doses. Repeated administration of d-amphetamine (0.2, 0.8 or 1.6 mg/rat/day) completely attenuated the overall intake-decreasing effects of the drug; the time taken for recovery of total intake increased with increasing dose. Despite complete tolerance to its overall intake-decreasing effects, d-amphetamine produced persistent dose-related effects on the distribution of intake within sessions that were only partially attenuated with continued daily administration of the drug. Tolerance to the overall intake-decreasing effect of 1.6 mg was accompanied by parallel shifts toward larger doses in the dose-effect functions for total water intake and for the within-session distribution of intake. Redetermination of the dose-effect functions at several times after the repeated administration of 1.6 mg generally showed that tolerance of d-amphetamine was lost within 25 to 57 days after discontinuation of the drug."} {"id": "PMID:1271283", "title": "Tolerance to the respiratory effects of marijuana in man.", "content": "The respiratory depressant effect of marijuana was studied by means of carbon dioxide respiratory response curves in eight healthy male subjects participating in a study of the effects of a 90-day ad libitum intoxication to marijuana. Subjects were studied in the morning after refraining from marijuana use since the previous evening. Respiratory response curves were done before smoking and at 15, 30 and 60 minutes after smoking two 900-mg cigarettes containing 2.2% delta9-tetrahydrocannabinol. Studies were conducted 2 to 3, 5 to 6 and 8 to 9 weeks after onset of intoxication. There was a significant change from base-line controls, indicating respiratory depression following marijuana smoking. A significant change in the time-effect curve over these three study sessions, indicative of tolerance, was noted. The degree of pulse elevation also decreased over the three study sessions, but this decrease in effect was not statistically significant.", "contents": "Tolerance to the respiratory effects of marijuana in man. The respiratory depressant effect of marijuana was studied by means of carbon dioxide respiratory response curves in eight healthy male subjects participating in a study of the effects of a 90-day ad libitum intoxication to marijuana. Subjects were studied in the morning after refraining from marijuana use since the previous evening. Respiratory response curves were done before smoking and at 15, 30 and 60 minutes after smoking two 900-mg cigarettes containing 2.2% delta9-tetrahydrocannabinol. Studies were conducted 2 to 3, 5 to 6 and 8 to 9 weeks after onset of intoxication. There was a significant change from base-line controls, indicating respiratory depression following marijuana smoking. A significant change in the time-effect curve over these three study sessions, indicative of tolerance, was noted. The degree of pulse elevation also decreased over the three study sessions, but this decrease in effect was not statistically significant."} {"id": "PMID:1271284", "title": "Differential effects of ethanol and mannitol on contraction of arterial smooth muscle.", "content": "The present work, using isolated rat aortic strips, indicates that ethanol can inhibit development of spontaneous mechanical activity, induce contractions which are not inhibited by specific amine antagonists and potentiate or inhibit contractions induced by epinephrine and vasopressin. In addition, the data indicate that ethanol can attenuate contractions induced by K+ and can inhibit Ca++-induced contractions of K+-depolarized rat aortic strips. Experiments with a nonpenetrating substance, mannitol, suggest that the effects of ethanol are probably not solely a reflection of hyperosmolarity. Overall, the data could be used to suggest that ethanol may induce hyper- or hypoexcitability of aortic smooth muscle by affecting movement and/or translocation of Ca++.", "contents": "Differential effects of ethanol and mannitol on contraction of arterial smooth muscle. The present work, using isolated rat aortic strips, indicates that ethanol can inhibit development of spontaneous mechanical activity, induce contractions which are not inhibited by specific amine antagonists and potentiate or inhibit contractions induced by epinephrine and vasopressin. In addition, the data indicate that ethanol can attenuate contractions induced by K+ and can inhibit Ca++-induced contractions of K+-depolarized rat aortic strips. Experiments with a nonpenetrating substance, mannitol, suggest that the effects of ethanol are probably not solely a reflection of hyperosmolarity. Overall, the data could be used to suggest that ethanol may induce hyper- or hypoexcitability of aortic smooth muscle by affecting movement and/or translocation of Ca++."} {"id": "PMID:1271285", "title": "Reduced beta adrenergic responsiveness in rats treated with estrogenic agents.", "content": "Chronic treatment with ethynyl estradiol alone (48-50 mug/kg/day) and in combination with several doses of norethynodrel either attenuated or prevented the increase in tail skin temperature accompanying sC. administration of isoproterenol (200 mug/kg b.wt.) to male and female rats. Dietary administration of an oral contraceptive containing norethynodrel and mestranol (7.5 mg/kg of food) was also accompanied by an attenuated response to isoproterenol. Attenuation of the tail skin temperature response was present in all groups after 3 to 5 weeks of treatment but was detectable in the oral contraceptive-treated group after 1 week of treatment. All steroids and combinations, except norethynodrel administered alone (154 mug/kg/day), reduced body weight gain.", "contents": "Reduced beta adrenergic responsiveness in rats treated with estrogenic agents. Chronic treatment with ethynyl estradiol alone (48-50 mug/kg/day) and in combination with several doses of norethynodrel either attenuated or prevented the increase in tail skin temperature accompanying sC. administration of isoproterenol (200 mug/kg b.wt.) to male and female rats. Dietary administration of an oral contraceptive containing norethynodrel and mestranol (7.5 mg/kg of food) was also accompanied by an attenuated response to isoproterenol. Attenuation of the tail skin temperature response was present in all groups after 3 to 5 weeks of treatment but was detectable in the oral contraceptive-treated group after 1 week of treatment. All steroids and combinations, except norethynodrel administered alone (154 mug/kg/day), reduced body weight gain."} {"id": "PMID:1271286", "title": "Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides and morphine: antagonism by theophylline.", "content": "Adenosine and adenine nucleotides [adenosine-5'-monophosphate, adenosine-5'-diphosphate, adenosine triphosphate (ATP), cyclic adenosine 3',5'-monophosphate (dbcAMP)], but not (cAMP) and dibutyryl cyclic adenosine 3',5'-monosphosphate (dbcAMP)], but not adenine or inosine, inhibited the twitch response of the electrically stimulated guinea-pig myenteric plexus-longitudinal muscle preparation. With each agent except dbcAMP, inhibition was manifest muscle preparation. With each agent except dbcAMP, inhibition was manifest from 1 to 500 muM was maximal within 1 minute. For dbcAMP, higher concentrations were required (10-fold increase) and inhibition was maximal after 20 to 30 minutes. Theophylline (0.05-0.5 mM) both reversed and prevented the inhibition produced by each of these agents. In higher concentrations (greater than 1 mM), theophylline itself depressed the twitch response. Neither propranolol nor phenoxybenzamine altered theophylline-induced depression, whereas phenoxybenzamine did not alter adenosine-induced inhibition. Adenosine, ATP, cAMP and theophylline (0.25 mM) did not alter acetylcholine-induced contractions, whereas a higher concentration of theophylline (2.5 mM) inhibited contractions. Theophylline (up to 0.5 mM) did not antagonize epinephrine- or dopamine-induced inhibition of the twitch response, but did antagonize morphine-induced inhibition. These findings suggest that adenosine and related nucleotides act at a common receptor site at which theophylline acts as a competitive antagonist and that there is a link between morphine and adenine nucleotide action in this preparation.", "contents": "Inhibition of acetylcholine release from cholinergic nerves by adenosine, adenine nucleotides and morphine: antagonism by theophylline. Adenosine and adenine nucleotides [adenosine-5'-monophosphate, adenosine-5'-diphosphate, adenosine triphosphate (ATP), cyclic adenosine 3',5'-monophosphate (dbcAMP)], but not (cAMP) and dibutyryl cyclic adenosine 3',5'-monosphosphate (dbcAMP)], but not adenine or inosine, inhibited the twitch response of the electrically stimulated guinea-pig myenteric plexus-longitudinal muscle preparation. With each agent except dbcAMP, inhibition was manifest muscle preparation. With each agent except dbcAMP, inhibition was manifest from 1 to 500 muM was maximal within 1 minute. For dbcAMP, higher concentrations were required (10-fold increase) and inhibition was maximal after 20 to 30 minutes. Theophylline (0.05-0.5 mM) both reversed and prevented the inhibition produced by each of these agents. In higher concentrations (greater than 1 mM), theophylline itself depressed the twitch response. Neither propranolol nor phenoxybenzamine altered theophylline-induced depression, whereas phenoxybenzamine did not alter adenosine-induced inhibition. Adenosine, ATP, cAMP and theophylline (0.25 mM) did not alter acetylcholine-induced contractions, whereas a higher concentration of theophylline (2.5 mM) inhibited contractions. Theophylline (up to 0.5 mM) did not antagonize epinephrine- or dopamine-induced inhibition of the twitch response, but did antagonize morphine-induced inhibition. These findings suggest that adenosine and related nucleotides act at a common receptor site at which theophylline acts as a competitive antagonist and that there is a link between morphine and adenine nucleotide action in this preparation."} {"id": "PMID:1271287", "title": "Ventricular electrophysiology of quinidine-propranolol combinations in the dog heart.", "content": "The effects of quinidine and propranolol, singly and in combination, on certain electrophysiological responses were studied in open-chest dogs. Parameters measured were the diastolic threshold, conduction time, excitability and functional refractory period of canine right ventricular muscle. Potentiation was judged to have occurred if the combination of a half-dose of quinidine plus a half-dose of propranolol produced a significantly greater response than the full dose of either quinidine or propranolol. Two combinations were employed in this study: combination I contained 2.5 mg/kg of quinidine plus 0.1 mg/kg of propranolol while combination II contained 5.0 mg/kg of quinidine plus 0.2 mg/kg of propranolol. Results of the study indicated that combination II potentiated the activity of quinidine and propranolol to depress excitability, increase conduction time and prolong refractoriness. However, combination I only potentiated the change in refractory state. Neither combination potentiated the individual drug action to increase the diastolic threshold. From the results of this study, it may be concluded that the combination was especially effective in prolonging ventricular refractoriness which may account to a significant degree for the enhanced therapeutic effectiveness of the combination in resistant ventricular arrhythmias.", "contents": "Ventricular electrophysiology of quinidine-propranolol combinations in the dog heart. The effects of quinidine and propranolol, singly and in combination, on certain electrophysiological responses were studied in open-chest dogs. Parameters measured were the diastolic threshold, conduction time, excitability and functional refractory period of canine right ventricular muscle. Potentiation was judged to have occurred if the combination of a half-dose of quinidine plus a half-dose of propranolol produced a significantly greater response than the full dose of either quinidine or propranolol. Two combinations were employed in this study: combination I contained 2.5 mg/kg of quinidine plus 0.1 mg/kg of propranolol while combination II contained 5.0 mg/kg of quinidine plus 0.2 mg/kg of propranolol. Results of the study indicated that combination II potentiated the activity of quinidine and propranolol to depress excitability, increase conduction time and prolong refractoriness. However, combination I only potentiated the change in refractory state. Neither combination potentiated the individual drug action to increase the diastolic threshold. From the results of this study, it may be concluded that the combination was especially effective in prolonging ventricular refractoriness which may account to a significant degree for the enhanced therapeutic effectiveness of the combination in resistant ventricular arrhythmias."} {"id": "PMID:1271288", "title": "Comparative species studies on the effect of monovalent cations and ouabain on cardiac Na+, K+-adenosine triphosphatase and contractile force.", "content": "The effects of ouabain, Rb+ and Tl+ on Na+, K+-adenosine triphosphatase (Na+,K+-ATPase; Mg++-dependent, Na+,K+-activated ATP phosphohydrolase, EC 3.6.1.3) and contractile force were compared in guinea-pig and rat hearts. Although ouabain produced a dose-dependent positive inotropic effect in rat as well as in guinea-pig atrial preparations, concentrations of ouabain needed to produce comparable positive inotropic effects were more than an order of magnitude higher in rats than in guinea pigs. Additionally, the time to reach the plateau of the inotropic response was significantly shorter in rat than in guinea-pig atrial preparations. Concentrations of ouabain needed to produce comparable inhibition of cardiac Na+, K+-ATPase in vitro observed with partially purified cardiac enzyme preparations were also more than an order to magnitude higher in rats than in guinea pigs.", "contents": "Comparative species studies on the effect of monovalent cations and ouabain on cardiac Na+, K+-adenosine triphosphatase and contractile force. The effects of ouabain, Rb+ and Tl+ on Na+, K+-adenosine triphosphatase (Na+,K+-ATPase; Mg++-dependent, Na+,K+-activated ATP phosphohydrolase, EC 3.6.1.3) and contractile force were compared in guinea-pig and rat hearts. Although ouabain produced a dose-dependent positive inotropic effect in rat as well as in guinea-pig atrial preparations, concentrations of ouabain needed to produce comparable positive inotropic effects were more than an order of magnitude higher in rats than in guinea pigs. Additionally, the time to reach the plateau of the inotropic response was significantly shorter in rat than in guinea-pig atrial preparations. Concentrations of ouabain needed to produce comparable inhibition of cardiac Na+, K+-ATPase in vitro observed with partially purified cardiac enzyme preparations were also more than an order to magnitude higher in rats than in guinea pigs."} {"id": "PMID:1271289", "title": "Elimination and distribution of phenylbutazone in rats during the course of adjuvant-induced arthritis.", "content": "The elimination and distribution of phenylbutazone after administration of a single intravenous dose of 25 mg/kg was investigated before and at different stages of adjuvant-induced arthritis in the same group of rats. In other groups which were studied concurrently, the cytochrome P-450 and b5 levels and ethylmorphine demethylation of liver microsomes were determined. Total plasma protein and albumin concentrations were monitored and the binding of phenylbutazone to plasma proteins was investigated. In the acute phase of adjuvant-induced arthritis, there was 1) a pronounced decrease in the elimination rate of phenylbutazone and 2) a marked increase in the apparent volume of distribution. The former could be explained by a reduced rate of hepatic biotransformation of phenylbutazone. A pronounced decrease in the microsomal cytochrome content and a slow rate of ethylmorphine demethylation is in agreement with this assumption. The latter appeared to be a result of the reduced binding capacity of the rat plasma due to the decrease in albumin concentration. The cytochrome content of liver microsomes and the plasma albumin concentration, however, were restored when arthritis reached its chronic phase. Consequently, an impairment of the elmination and distribution of phenylbutazone was no longer apparent.", "contents": "Elimination and distribution of phenylbutazone in rats during the course of adjuvant-induced arthritis. The elimination and distribution of phenylbutazone after administration of a single intravenous dose of 25 mg/kg was investigated before and at different stages of adjuvant-induced arthritis in the same group of rats. In other groups which were studied concurrently, the cytochrome P-450 and b5 levels and ethylmorphine demethylation of liver microsomes were determined. Total plasma protein and albumin concentrations were monitored and the binding of phenylbutazone to plasma proteins was investigated. In the acute phase of adjuvant-induced arthritis, there was 1) a pronounced decrease in the elimination rate of phenylbutazone and 2) a marked increase in the apparent volume of distribution. The former could be explained by a reduced rate of hepatic biotransformation of phenylbutazone. A pronounced decrease in the microsomal cytochrome content and a slow rate of ethylmorphine demethylation is in agreement with this assumption. The latter appeared to be a result of the reduced binding capacity of the rat plasma due to the decrease in albumin concentration. The cytochrome content of liver microsomes and the plasma albumin concentration, however, were restored when arthritis reached its chronic phase. Consequently, an impairment of the elmination and distribution of phenylbutazone was no longer apparent."} {"id": "PMID:1271290", "title": "Binocular visual mechanisms in cortical areas I and II of the sheep.", "content": "1. Units were recorded in the primary and secondary visual areas (V1 and V2) of the sheep. They were stimulated binocularly, using an adjustable prism to vary the disparity. 2. Cells in V1 responded optimally to stimuli with very small or zero disparities, but cells in V2 frequently preferred disparities of several degrees crossed or uncrossed. Many cells in V2 were particularly selective to disparity, often giving no response to a monocular stimulus. 3. Cells preferring the same disparity occur in discrete columns, about 400 muM wide. Changes between columns result from a step displacement of the receptive field of one eye. The disparities encoded in successive columns seem to follow a regular sequence: crossed, zero, uncrossed, zero, etc. 4. In both V1 and V2, cells are clustered, perhaps in columns, according to their orientation preference and ocular dominance. In V2, the constant disparity columns appear to be independent of the orientation clusters.", "contents": "Binocular visual mechanisms in cortical areas I and II of the sheep. 1. Units were recorded in the primary and secondary visual areas (V1 and V2) of the sheep. They were stimulated binocularly, using an adjustable prism to vary the disparity. 2. Cells in V1 responded optimally to stimuli with very small or zero disparities, but cells in V2 frequently preferred disparities of several degrees crossed or uncrossed. Many cells in V2 were particularly selective to disparity, often giving no response to a monocular stimulus. 3. Cells preferring the same disparity occur in discrete columns, about 400 muM wide. Changes between columns result from a step displacement of the receptive field of one eye. The disparities encoded in successive columns seem to follow a regular sequence: crossed, zero, uncrossed, zero, etc. 4. In both V1 and V2, cells are clustered, perhaps in columns, according to their orientation preference and ocular dominance. In V2, the constant disparity columns appear to be independent of the orientation clusters."} {"id": "PMID:1271291", "title": "Impedance components in longitudinal direction in the guinea-pig taenia coli.", "content": "1. When the tissue impedance of the guinea-pig taenia coli was measured across a 2 mm sucrose gap in a longitudinal direction, the impedance locus could be fitted by two different circular arcs. Their characteristic frequencies were about 0-6 and 240 Hz after 60 min superfusion with sucrose solution. From the effects of changing the width of sucrose gap and of transection of tissue, and also from taking the difference between impedances measured at two distances, it was concluded that the low-frequency locus corresponds to the transverse impedance of the plasma membrane and the high-frequency locus to the longitudinal tissue impedance. 2. A change in the longitudinal tissue impedance was measured during superfusion with sucrose solution, using a frequency range between 5 Hz and 10 kHz. The admittance decreased with time of superfusion and this time course could be expressed by the sum of three exponential terms. The fastest component, having a time constant of 1-3 min at 10 kHz, was interpreted to correspond to a process of wash-out of extracellular medium. 3. Admittances at zero and infinite frequencies were obtained from the impedance locus. The decrease in these admittances with the time was analysed and the values at the start of washing were obtained by extrapolating the admittance change to zero time. 4. From these values it was estimated that the myoplasmic resistance was 214 omega cm, the junctional resistance 372 omega cm, and the junctional capacity 3-1 muF/cm at 25 degrees C. In these calculations the equivalent circuit of tissue was assumed to be expressed by two components in series: one for the myoplasmic resistance and the other for the junction which has the junctional resistance and capacity in parallel. 5. After 90 min superfusion with sucrose solution, the total tissue impedance measured at zero frequency was increased from 586 to 3034 omega cm. In the total impedance the myoplasmic resistance was increased from 214 to 914 omega cm and the junctional resistance from 372 to 2120 omega cm. Thus, the change in junctional resistance was greater than that in myoplasmic resistance during superfusion of sucrose solution.", "contents": "Impedance components in longitudinal direction in the guinea-pig taenia coli. 1. When the tissue impedance of the guinea-pig taenia coli was measured across a 2 mm sucrose gap in a longitudinal direction, the impedance locus could be fitted by two different circular arcs. Their characteristic frequencies were about 0-6 and 240 Hz after 60 min superfusion with sucrose solution. From the effects of changing the width of sucrose gap and of transection of tissue, and also from taking the difference between impedances measured at two distances, it was concluded that the low-frequency locus corresponds to the transverse impedance of the plasma membrane and the high-frequency locus to the longitudinal tissue impedance. 2. A change in the longitudinal tissue impedance was measured during superfusion with sucrose solution, using a frequency range between 5 Hz and 10 kHz. The admittance decreased with time of superfusion and this time course could be expressed by the sum of three exponential terms. The fastest component, having a time constant of 1-3 min at 10 kHz, was interpreted to correspond to a process of wash-out of extracellular medium. 3. Admittances at zero and infinite frequencies were obtained from the impedance locus. The decrease in these admittances with the time was analysed and the values at the start of washing were obtained by extrapolating the admittance change to zero time. 4. From these values it was estimated that the myoplasmic resistance was 214 omega cm, the junctional resistance 372 omega cm, and the junctional capacity 3-1 muF/cm at 25 degrees C. In these calculations the equivalent circuit of tissue was assumed to be expressed by two components in series: one for the myoplasmic resistance and the other for the junction which has the junctional resistance and capacity in parallel. 5. After 90 min superfusion with sucrose solution, the total tissue impedance measured at zero frequency was increased from 586 to 3034 omega cm. In the total impedance the myoplasmic resistance was increased from 214 to 914 omega cm and the junctional resistance from 372 to 2120 omega cm. Thus, the change in junctional resistance was greater than that in myoplasmic resistance during superfusion of sucrose solution."} {"id": "PMID:1271292", "title": "A study of peripheral input to and its control by post-ganglionic neurones of the inferior mesenteric ganglion.", "content": "1. Intracellular recordings were made, in vitro, from neurones of guinea-pig inferior mesenteric ganglia (IMG) attached, via the lumbar colonic nerves, to segments of distal colon. 2. 'Spontaneous' synaptic input from colonic afferent fibres was observed in 79% of the neurones tested. In any given preparation, the level and pattern of this synaptic input to different neurones varied considerably. 3. Superfusion of colonic segments with drugs (papaverine, isoprenaline, and adenosine triphosphate) which reduce colonic motility decreased colonic afferent input to IMG neurones. 4. Superfusion of colonic segments with acetylcholine or stimulation of pelvic nerves, both of which increase colonic motility, increased colonic afferent input to IMG neurones. 5. Superfusion of colonic segments with either atropine or tubocurarine reduced the level of 'spontaneous', colonic afferent input. However, distension of these relaxed segments increased the colonic afferent input. 6. Repetitive stimulation of preganglionic inputs to the IMG inhibited afferent input from drug relaxed segments of colon that were moderately distended by the injection of air into the lumen. Superfusion of the colon with phentolamine blocked this inhibition. 7. The results of this study suggest that IMG neurones receive afferent input from mechanoreceptors located in the distal colon and that the mechanosensitivity of this afferent pathway is in part controlled by efferent noradrenergic neurones of the IMG. The IMG-colon neural circuitry can therefore be considered to form a feed-back control system which participates in the regulation of colonic motility.", "contents": "A study of peripheral input to and its control by post-ganglionic neurones of the inferior mesenteric ganglion. 1. Intracellular recordings were made, in vitro, from neurones of guinea-pig inferior mesenteric ganglia (IMG) attached, via the lumbar colonic nerves, to segments of distal colon. 2. 'Spontaneous' synaptic input from colonic afferent fibres was observed in 79% of the neurones tested. In any given preparation, the level and pattern of this synaptic input to different neurones varied considerably. 3. Superfusion of colonic segments with drugs (papaverine, isoprenaline, and adenosine triphosphate) which reduce colonic motility decreased colonic afferent input to IMG neurones. 4. Superfusion of colonic segments with acetylcholine or stimulation of pelvic nerves, both of which increase colonic motility, increased colonic afferent input to IMG neurones. 5. Superfusion of colonic segments with either atropine or tubocurarine reduced the level of 'spontaneous', colonic afferent input. However, distension of these relaxed segments increased the colonic afferent input. 6. Repetitive stimulation of preganglionic inputs to the IMG inhibited afferent input from drug relaxed segments of colon that were moderately distended by the injection of air into the lumen. Superfusion of the colon with phentolamine blocked this inhibition. 7. The results of this study suggest that IMG neurones receive afferent input from mechanoreceptors located in the distal colon and that the mechanosensitivity of this afferent pathway is in part controlled by efferent noradrenergic neurones of the IMG. The IMG-colon neural circuitry can therefore be considered to form a feed-back control system which participates in the regulation of colonic motility."} {"id": "PMID:1271293", "title": "Unmyelinated fibres in the sacral 3 and caudal 1 ventral roots of the cat.", "content": "1. 29% of the axons in the S3 and Ca 1 caudal ventral roots of the cat are unmyelinated. 2. Approximately one half of these unmyelinated axons survive in the proximal stump of a sectioned ventral root and are regarded as unmyelinated preganglionic efferents. 3. At least 27% of the preganglionic efferents in segments S3 and Ca 1 are unmyelinated. 4. The other half of the ventral root unmyelinated axons arise from dorsal root ganglion cells and survive in the distal stump of a sectioned ventral root. 5. The data in 4, combined with the receptive field data in our companion paper, show that these unmyelinated fibres are sensory. 6. Since 15% of the ventral root axons are sensory, the Law of Bell and Magendie cannot be regarded as an accurate description of the organization of these ventral roots.", "contents": "Unmyelinated fibres in the sacral 3 and caudal 1 ventral roots of the cat. 1. 29% of the axons in the S3 and Ca 1 caudal ventral roots of the cat are unmyelinated. 2. Approximately one half of these unmyelinated axons survive in the proximal stump of a sectioned ventral root and are regarded as unmyelinated preganglionic efferents. 3. At least 27% of the preganglionic efferents in segments S3 and Ca 1 are unmyelinated. 4. The other half of the ventral root unmyelinated axons arise from dorsal root ganglion cells and survive in the distal stump of a sectioned ventral root. 5. The data in 4, combined with the receptive field data in our companion paper, show that these unmyelinated fibres are sensory. 6. Since 15% of the ventral root axons are sensory, the Law of Bell and Magendie cannot be regarded as an accurate description of the organization of these ventral roots."} {"id": "PMID:1271294", "title": "Further studies of the potential-dependence of the sodium-induced membrane current in snail neurones.", "content": "1. The potential-dependence of the membrane current induced by intracellular injections of sodium ions was studied on giant neurones of the snail Helix pomatia. This current decreases with membrane hyperpolarization at room temperature and can be reversed at sufficiently negative holding potentials. The same injections at 7 degrees C, as well as injections of lithium or potassium ions do not induce membrane currents and do not increase membrane conductance. 2. An increase in the amount of injected sodium changes the potential-dependence of the induced membrane currents. Small injections (about 1 muC) induce a current that does not depend upon the membrane potential. Further increase in the injection size not only increases the induced current but also enhances its potential-dependence and often reveals the existence of a reversal potential. The latter reaches -60 to -65 mV with large sodium injections. 3. An increase in extracellular potassium concentration from 4 to 8 mM shifts the reversal potential 17 mV in the depolarizing direction, and a decrease from 4 to 2 mM shifts it 14 mV in the hyperpolarizing direction. Replacement of potassium by rubidium or elimination of sodium ions from the outside solution, does not affect the induced current or its potential-dependence. 4. The coefficient of electrogenicity (the ratio between the amount of charge transferred by the sodium-induced membrane current and the amount brought into the cell during the injection) increases with an increase in the injection size if the membrane potential is clamped near the resting potential level. This relation is reversed when the holding potential is -80 mV. The reversal takes place at holding potentials near -60 mV. 5. 10 mM TEA does not affect the induced current and its potential-dependence. 6. It is suggested that the potential-dependence of the sodium-induced membrane current is a result of a specific increase in the membrane potassium conductance that is coupled with high activity of the sodium pump.", "contents": "Further studies of the potential-dependence of the sodium-induced membrane current in snail neurones. 1. The potential-dependence of the membrane current induced by intracellular injections of sodium ions was studied on giant neurones of the snail Helix pomatia. This current decreases with membrane hyperpolarization at room temperature and can be reversed at sufficiently negative holding potentials. The same injections at 7 degrees C, as well as injections of lithium or potassium ions do not induce membrane currents and do not increase membrane conductance. 2. An increase in the amount of injected sodium changes the potential-dependence of the induced membrane currents. Small injections (about 1 muC) induce a current that does not depend upon the membrane potential. Further increase in the injection size not only increases the induced current but also enhances its potential-dependence and often reveals the existence of a reversal potential. The latter reaches -60 to -65 mV with large sodium injections. 3. An increase in extracellular potassium concentration from 4 to 8 mM shifts the reversal potential 17 mV in the depolarizing direction, and a decrease from 4 to 2 mM shifts it 14 mV in the hyperpolarizing direction. Replacement of potassium by rubidium or elimination of sodium ions from the outside solution, does not affect the induced current or its potential-dependence. 4. The coefficient of electrogenicity (the ratio between the amount of charge transferred by the sodium-induced membrane current and the amount brought into the cell during the injection) increases with an increase in the injection size if the membrane potential is clamped near the resting potential level. This relation is reversed when the holding potential is -80 mV. The reversal takes place at holding potentials near -60 mV. 5. 10 mM TEA does not affect the induced current and its potential-dependence. 6. It is suggested that the potential-dependence of the sodium-induced membrane current is a result of a specific increase in the membrane potassium conductance that is coupled with high activity of the sodium pump."} {"id": "PMID:1271295", "title": "Glycine-mediated inhibitory transmission of group 1A-excited inhibitory interneurones by Renshaw cells.", "content": "1. Electrophysiological and micro-electrophoretic studies were carried out in anaesthetized cats on spinal interneurones which were monosynaptically activated from group 1 muscle afferents and recurrently inhibited by Renshaw cells. 2. The recurrent inhibition was blocked by the iontophoretic administration of strychnine, which also blocked the action of glycine. 3. The time course of the block of synaptic inhibition by strychnine was slower than the block of glycine evoked inhibition. The significance of this observation in terms of the location of the inhibitory synapses is discussed. 4. The observation that recurrent inhibition of motoneurones and of interneurones is blocked by strychnine whereas the mutual inhibition of Renshaw cells is not is discussed in relation to the proposal that the nature of the post-synaptic inhibitory receptor is not determined solely by the innervating neurone, which is the Renshaw cell in all three instances. 5. The recurrent inhibition of the interneurones was not blocked by the iontophoretic administration of bicuculline, but difficulties were encountered in demonstrating that this agent consistently antagonized the inhibitory effects of GABA.", "contents": "Glycine-mediated inhibitory transmission of group 1A-excited inhibitory interneurones by Renshaw cells. 1. Electrophysiological and micro-electrophoretic studies were carried out in anaesthetized cats on spinal interneurones which were monosynaptically activated from group 1 muscle afferents and recurrently inhibited by Renshaw cells. 2. The recurrent inhibition was blocked by the iontophoretic administration of strychnine, which also blocked the action of glycine. 3. The time course of the block of synaptic inhibition by strychnine was slower than the block of glycine evoked inhibition. The significance of this observation in terms of the location of the inhibitory synapses is discussed. 4. The observation that recurrent inhibition of motoneurones and of interneurones is blocked by strychnine whereas the mutual inhibition of Renshaw cells is not is discussed in relation to the proposal that the nature of the post-synaptic inhibitory receptor is not determined solely by the innervating neurone, which is the Renshaw cell in all three instances. 5. The recurrent inhibition of the interneurones was not blocked by the iontophoretic administration of bicuculline, but difficulties were encountered in demonstrating that this agent consistently antagonized the inhibitory effects of GABA."} {"id": "PMID:1271296", "title": "Influence of changes in external potassium and chloride ions on membrane potential and intracellular potassium ion activity in rabbit ventricular muscle.", "content": "1. The membrane responses of rabbit papillary muscles to rapid changes in [K](o) and [Cl](o) were measured with open-tipped micropipettes and with closed micropipettes made from K-selective glass.2. The muscle cells behaved primarily as a K electrode, and responses to changes in [K](o) with constant [Cl](o) or with constant [K](o) x [Cl](o) were substantially the same.3. When [Cl](o) was changed at a constant [K](o) the membrane potentials changed rapidly and symmetrically by a small value and remained constant for 30 min.4. Measurement of potential with K(+)-selective micro-electrodes in these experiments showed no change in intracellular K activity. In addition to permitting calculation of K permeability, these measurements reassured us that the K(+)-selective electrodes were well insulated and not influenced by electrical shunts at the impalement site.5. Although the membrane response to changes in [Cl](o) was small, it was possible to calculate that the permeability ratio (P(Cl)/P(K)), was 0.11. The Cl and K conductances were about 0.015 mmho/cm(2) and 0.09 mmho/cm(2) respectively, resulting in a conductance ratio (g(Cl)/g(K)) of about 0.17.6. The time course of depolarization by increase in [K](o) was rapid (half-time 5 sec), but repolarization on return to lower [K](o) was much slower (half-time 50 sec). The depolarization time course was easily fitted by the potential change calculated by assuming the need for K diffusion into the extracellular spaces and taking account of the logarithmic relation between membrane potential and [K](o). These calculations did not fit the time course of repolarization, which was slowed in the fashion expected from an inward-rectifying membrane.7. The influence of [K](i) on membrane potential was investigated by changes in tonicity of the external solution. Hypotonic solution produced a change in intracellular K activity close to that produced by ideal water movement. However, in hypertonic solution, intracellular K activity did not rise as much as predicted, suggesting a change in intracellular activity coefficient.", "contents": "Influence of changes in external potassium and chloride ions on membrane potential and intracellular potassium ion activity in rabbit ventricular muscle. 1. The membrane responses of rabbit papillary muscles to rapid changes in [K](o) and [Cl](o) were measured with open-tipped micropipettes and with closed micropipettes made from K-selective glass.2. The muscle cells behaved primarily as a K electrode, and responses to changes in [K](o) with constant [Cl](o) or with constant [K](o) x [Cl](o) were substantially the same.3. When [Cl](o) was changed at a constant [K](o) the membrane potentials changed rapidly and symmetrically by a small value and remained constant for 30 min.4. Measurement of potential with K(+)-selective micro-electrodes in these experiments showed no change in intracellular K activity. In addition to permitting calculation of K permeability, these measurements reassured us that the K(+)-selective electrodes were well insulated and not influenced by electrical shunts at the impalement site.5. Although the membrane response to changes in [Cl](o) was small, it was possible to calculate that the permeability ratio (P(Cl)/P(K)), was 0.11. The Cl and K conductances were about 0.015 mmho/cm(2) and 0.09 mmho/cm(2) respectively, resulting in a conductance ratio (g(Cl)/g(K)) of about 0.17.6. The time course of depolarization by increase in [K](o) was rapid (half-time 5 sec), but repolarization on return to lower [K](o) was much slower (half-time 50 sec). The depolarization time course was easily fitted by the potential change calculated by assuming the need for K diffusion into the extracellular spaces and taking account of the logarithmic relation between membrane potential and [K](o). These calculations did not fit the time course of repolarization, which was slowed in the fashion expected from an inward-rectifying membrane.7. The influence of [K](i) on membrane potential was investigated by changes in tonicity of the external solution. Hypotonic solution produced a change in intracellular K activity close to that produced by ideal water movement. However, in hypertonic solution, intracellular K activity did not rise as much as predicted, suggesting a change in intracellular activity coefficient."} {"id": "PMID:1271297", "title": "The antecedents of anger in a sample of college students.", "content": "Eighty-three college students were surveyed in an attempt to identify the situations that elicit anger or a loss of temper. The 356 responses were sorted into seven rational categories with substantial interrater reliability. There were no significant sex differences; however, there were more antecedents reported for anger than for loss of temper. On a self-rating scale a high percent of Ss gave a benign report on the frequency of their anger arousal and loss of temper. However, the intensity of anger was reported as greater than that of others by 32% of the males and 20% of the females.", "contents": "The antecedents of anger in a sample of college students. Eighty-three college students were surveyed in an attempt to identify the situations that elicit anger or a loss of temper. The 356 responses were sorted into seven rational categories with substantial interrater reliability. There were no significant sex differences; however, there were more antecedents reported for anger than for loss of temper. On a self-rating scale a high percent of Ss gave a benign report on the frequency of their anger arousal and loss of temper. However, the intensity of anger was reported as greater than that of others by 32% of the males and 20% of the females."} {"id": "PMID:1271298", "title": "Relationship of self-concepts of three-, four-, and five-year-old children with mother, father, and teacher percepts.", "content": "Ss were 46 preschool boys and girls, ages three, four, and five years, in a child and family development center. Each child, his mother, father, and teacher were administered, separately, 18 select items from the primary factor in the I Feel-Me Feel self-concept inventory. Results indicated that the childrens' self/social constructs scores were very stable but did not correlate with scores of mother, father, and teacher. The adult percepts of the child's self-concept were highly correlated ( less than .05) among themselves, but they were not in the same system of relationships with the children.", "contents": "Relationship of self-concepts of three-, four-, and five-year-old children with mother, father, and teacher percepts. Ss were 46 preschool boys and girls, ages three, four, and five years, in a child and family development center. Each child, his mother, father, and teacher were administered, separately, 18 select items from the primary factor in the I Feel-Me Feel self-concept inventory. Results indicated that the childrens' self/social constructs scores were very stable but did not correlate with scores of mother, father, and teacher. The adult percepts of the child's self-concept were highly correlated ( less than .05) among themselves, but they were not in the same system of relationships with the children."} {"id": "PMID:1271299", "title": "Anxiety as a function of environmental noise and social interaction.", "content": "In a study to investigate environmental noise and social interaction as simultaneous stressors affecting anxiety, three independent groups of college students (N = 48 men and women) participated in the simulation game Starpower while exposed to different levels of background noise. Intermittent white noise at 61 dB(A) and 75 dB(A) was used for the Noisy and Very Noisy conditions, respectively, and the ambient noise level of 51 dB(A) was used for Quiet. The State-Trait Anxiety Inventory, administered before and after playing the game, was used as a direct, subjective measure of anxiety. Relatively low levels of noise superimposed on the stress of social interaction influenced the level of anxiety experienced by the Ss. Groups subjected to noisier environments reported significantly stronger feelings of anxiety than those in quieter conditions (p less than .05). Ss' eyeblink rate, used as an indirect, physiological indicator of anxiety, was not significantly affected by the stress levels produced in this experiment.", "contents": "Anxiety as a function of environmental noise and social interaction. In a study to investigate environmental noise and social interaction as simultaneous stressors affecting anxiety, three independent groups of college students (N = 48 men and women) participated in the simulation game Starpower while exposed to different levels of background noise. Intermittent white noise at 61 dB(A) and 75 dB(A) was used for the Noisy and Very Noisy conditions, respectively, and the ambient noise level of 51 dB(A) was used for Quiet. The State-Trait Anxiety Inventory, administered before and after playing the game, was used as a direct, subjective measure of anxiety. Relatively low levels of noise superimposed on the stress of social interaction influenced the level of anxiety experienced by the Ss. Groups subjected to noisier environments reported significantly stronger feelings of anxiety than those in quieter conditions (p less than .05). Ss' eyeblink rate, used as an indirect, physiological indicator of anxiety, was not significantly affected by the stress levels produced in this experiment."} {"id": "PMID:1271300", "title": "Gaze as a function of conversation and degree of love.", "content": "The possibility that Rubin's findings of greater mutual gazing between strong than weak lovers and between strangers could be attributed to the occurrence of more conversation in strong love conditions was tested. Ss were selected from an undergraduate population. Ten strong love couples, determined through the use of Rubin's love scale, were compared to 10 pairs of unacquainted Ss for the amount of mutual eye contact, as well as conversation time and time spent in pure gazing without conversation. It was found that lovers did converse more with each other than with strangers. However, they also spent more time in pure gazing during periods of silence, lending credence to Rubin's results. The methodological implications of using videotape for eye contact studies were also discussed.", "contents": "Gaze as a function of conversation and degree of love. The possibility that Rubin's findings of greater mutual gazing between strong than weak lovers and between strangers could be attributed to the occurrence of more conversation in strong love conditions was tested. Ss were selected from an undergraduate population. Ten strong love couples, determined through the use of Rubin's love scale, were compared to 10 pairs of unacquainted Ss for the amount of mutual eye contact, as well as conversation time and time spent in pure gazing without conversation. It was found that lovers did converse more with each other than with strangers. However, they also spent more time in pure gazing during periods of silence, lending credence to Rubin's results. The methodological implications of using videotape for eye contact studies were also discussed."} {"id": "PMID:1271301", "title": "The modal personality of urban black middle-class elementary school children.", "content": "This study attemped to identify traits that might be described as \"typical\" of black elementary school children. With use of the Early School Personality Questionnaire, the mean and modal scores for 13 traits were determined for 59 girls and 61 boys selected from two urban areas in two sections of the country. All were children of black middle-class families and were six and eight years old. When compared to the expected scores for children of this age range, the group as a whole differed from the average expected scores on only four factors. Analysis of the traits by sex found that black middle-class boys differed from the standardization sample boys on four of the 13 factors, and girls on eight of the 13. It was concluded that black middle-class girls, although not very different from the boys, were quite different in personality from girls of other groups, while the boys differed very little. The black sample was significantly more aloof and shrewd than the standardization group. It might be that these are traits developed by parents in black middle-class children to help them cope with a color-discriminating environment.", "contents": "The modal personality of urban black middle-class elementary school children. This study attemped to identify traits that might be described as \"typical\" of black elementary school children. With use of the Early School Personality Questionnaire, the mean and modal scores for 13 traits were determined for 59 girls and 61 boys selected from two urban areas in two sections of the country. All were children of black middle-class families and were six and eight years old. When compared to the expected scores for children of this age range, the group as a whole differed from the average expected scores on only four factors. Analysis of the traits by sex found that black middle-class boys differed from the standardization sample boys on four of the 13 factors, and girls on eight of the 13. It was concluded that black middle-class girls, although not very different from the boys, were quite different in personality from girls of other groups, while the boys differed very little. The black sample was significantly more aloof and shrewd than the standardization group. It might be that these are traits developed by parents in black middle-class children to help them cope with a color-discriminating environment."} {"id": "PMID:1271302", "title": "The dimensionality of body-cathexis.", "content": "In an exploratory examination of the dimensionality of body perception in terms of satisfaction with body aspects, a principal components analysis was performed on data from 226 male and female college students. Results indicate that the complex of body aspects can be discussed in terms of a relatively small number of dimensions. The variable content of the factors is interpreted as suggesting the perceptual grouping of body aspects, and in this regard the similarities and differences between males and females are discussed and related to previous research on body-cathexis.", "contents": "The dimensionality of body-cathexis. In an exploratory examination of the dimensionality of body perception in terms of satisfaction with body aspects, a principal components analysis was performed on data from 226 male and female college students. Results indicate that the complex of body aspects can be discussed in terms of a relatively small number of dimensions. The variable content of the factors is interpreted as suggesting the perceptual grouping of body aspects, and in this regard the similarities and differences between males and females are discussed and related to previous research on body-cathexis."} {"id": "PMID:1271303", "title": "Fine-structural aspects of microgametogenesis of Eimeria magna in rabbits and in kidney cell cultures.", "content": "The fine-structural aspects of development of microgamonts of Eimeria magna were studied in kidney cell cultures and in experimentally infected rabbits. Spheroidal masses of gamont-like cytoplasm containing ribosomes, polyribosomes, and amylopectin granules were found within the parasitophorus vacuole; these bodies were apparently pinched off the surface of the gamont. Nucleoli were present in the early stages of nuclear division but disappeared as development proceeded.", "contents": "Fine-structural aspects of microgametogenesis of Eimeria magna in rabbits and in kidney cell cultures. The fine-structural aspects of development of microgamonts of Eimeria magna were studied in kidney cell cultures and in experimentally infected rabbits. Spheroidal masses of gamont-like cytoplasm containing ribosomes, polyribosomes, and amylopectin granules were found within the parasitophorus vacuole; these bodies were apparently pinched off the surface of the gamont. Nucleoli were present in the early stages of nuclear division but disappeared as development proceeded."} {"id": "PMID:1271304", "title": "Fine structure of Plasmodium gallinaceum in embryonic and neonate chicks.", "content": "The erythrocytic stages of Plasmdoium gallinaceum in chicken embryos injected with parasited blood either from a syringe-passaged infection in chickens or from a chicken infected with sporozoites were characterized by abnormal structure. Particularly evident were large, unstained vacuoles within the cytoplasm; these occurred with greatest frequency in schizonts. The presence of myelin bodies within these vacuoles was revealed by transmission electron microscopy; abnormal cytokinesis and aberrant merozoites provided additional evidence of the parasite's inability to develop naturally within the milieu of the embryonic erythrocytes. Fifty-five passages were necessary to restore normal structure of the parasites in embryos, while only 5 passages were required for such restoration in neonate chicks. The probable adaptation of the parasite to the proportions of hemoglobin of the adult chicken may be responsible for the abnormal growth in the immature host.", "contents": "Fine structure of Plasmodium gallinaceum in embryonic and neonate chicks. The erythrocytic stages of Plasmdoium gallinaceum in chicken embryos injected with parasited blood either from a syringe-passaged infection in chickens or from a chicken infected with sporozoites were characterized by abnormal structure. Particularly evident were large, unstained vacuoles within the cytoplasm; these occurred with greatest frequency in schizonts. The presence of myelin bodies within these vacuoles was revealed by transmission electron microscopy; abnormal cytokinesis and aberrant merozoites provided additional evidence of the parasite's inability to develop naturally within the milieu of the embryonic erythrocytes. Fifty-five passages were necessary to restore normal structure of the parasites in embryos, while only 5 passages were required for such restoration in neonate chicks. The probable adaptation of the parasite to the proportions of hemoglobin of the adult chicken may be responsible for the abnormal growth in the immature host."} {"id": "PMID:1271305", "title": "Efficacy of antibiotics A204 sodium A28695A, and A204np against Coccidia of rabbits.", "content": "Three polycyclic, polyether, monocarboxylic acid antibiotics produced by and extracted from a strain of Streptomyces albus and designated A204 sodium, A28695A, or A204-np, were specifically tested for activity against hepatic and incidentally against intestinal coccidia of rabbits. All were effective in preventing infections and acceptable to young rabbits when prepared in pelleted feed. Weight gain, however, was not as good as inoculated, medicated rabbits as in noninoculated, nonmedicated controls. No gross pathologic changes were detected except in the livers of inoculated, nonmedicated controls which were severely infected on greatly enlarged. Livers of medicated rabbits were uninfected and normal in appearance and size.", "contents": "Efficacy of antibiotics A204 sodium A28695A, and A204np against Coccidia of rabbits. Three polycyclic, polyether, monocarboxylic acid antibiotics produced by and extracted from a strain of Streptomyces albus and designated A204 sodium, A28695A, or A204-np, were specifically tested for activity against hepatic and incidentally against intestinal coccidia of rabbits. All were effective in preventing infections and acceptable to young rabbits when prepared in pelleted feed. Weight gain, however, was not as good as inoculated, medicated rabbits as in noninoculated, nonmedicated controls. No gross pathologic changes were detected except in the livers of inoculated, nonmedicated controls which were severely infected on greatly enlarged. Livers of medicated rabbits were uninfected and normal in appearance and size."} {"id": "PMID:1271306", "title": "Eimeria tenella: host specificity in gallinaceous birds.", "content": "Eight species representing 8 genera of gallinaceous birds were used: Alectoris graeca; Colinus virginianus; Coturnix coturnix; Gallus gallus; Meleagris gallopavo; Numidia meleagris; Pavo cristatus; Phasianus colchicus. Three week-old birds were dosed with sporulated oocysts of Eimeria tenella Beltsville strain. At 4, 24, 48, 72, 96, 120 and 144, and 168 hr after inoculation, 1-3 infected birds and uninoculated controls of each species were killed by cardiac exsanguination. Pieces of intestines were fixed and examined for stages of E. tenella as stained paraffin sections or indirect fluorescent antibody preparations. Oocyst counts were made in droppings collected for the first 6 days of the patent period. Sporozoites were found in the lamina propria of some birds of 5 species at 4 hr postinoculation, but no stages were found thereafter except in the breeds of G. gallus and A. gracea. At 144 and 168 hr postinoculation, a few macrogametes were found in the ceca of 2 A. gracea, but no oocysts were found in the feces. No statistical difference was found between the number of oocysts produced/bird in the breeds of G. gallus examined. It is evident from these observations the E. tenella did not complete its life cycle in several close phylogenetic relatives of G. gallus, even though in other studies this parasite was found to complete its life cycle in cell cultures derived from the same birds.", "contents": "Eimeria tenella: host specificity in gallinaceous birds. Eight species representing 8 genera of gallinaceous birds were used: Alectoris graeca; Colinus virginianus; Coturnix coturnix; Gallus gallus; Meleagris gallopavo; Numidia meleagris; Pavo cristatus; Phasianus colchicus. Three week-old birds were dosed with sporulated oocysts of Eimeria tenella Beltsville strain. At 4, 24, 48, 72, 96, 120 and 144, and 168 hr after inoculation, 1-3 infected birds and uninoculated controls of each species were killed by cardiac exsanguination. Pieces of intestines were fixed and examined for stages of E. tenella as stained paraffin sections or indirect fluorescent antibody preparations. Oocyst counts were made in droppings collected for the first 6 days of the patent period. Sporozoites were found in the lamina propria of some birds of 5 species at 4 hr postinoculation, but no stages were found thereafter except in the breeds of G. gallus and A. gracea. At 144 and 168 hr postinoculation, a few macrogametes were found in the ceca of 2 A. gracea, but no oocysts were found in the feces. No statistical difference was found between the number of oocysts produced/bird in the breeds of G. gallus examined. It is evident from these observations the E. tenella did not complete its life cycle in several close phylogenetic relatives of G. gallus, even though in other studies this parasite was found to complete its life cycle in cell cultures derived from the same birds."} {"id": "PMID:1271307", "title": "Laboratory and field studies on Glugea stephani (Hagenmuller), a microsporidan parasite of pleuronectid flatfishes.", "content": "The microsporidan Glugea stephani is a common parasite of juvenile English sole (Parophrys vetulus) in Yaquina Bay, Oregon. Field observations indicated that fish became infected only in the upper estuary where summer temperatures were above 15C and the incidence of infection reached 79.8% in the late fall. Laboratory infections developed and parasite growth occurred only at or above 15C. The parasite was successfully transmitted to juvenile English sole by brine shrimp (Artemia salina) and amphipod (Corophium spinocorne) vectors as well as by direct ingestion of spores by the host. Infections that resulted from ingestion of spore-carrying vectors were much heavier than those resulting from the direct ingestion of spores. The speckled sanddab (Citharichthys stigmaeus), a nonpleuronectid flatfish, and chum salmon (Oncorhynchus keta) were refractory to G. stephani infection in the laboratory.", "contents": "Laboratory and field studies on Glugea stephani (Hagenmuller), a microsporidan parasite of pleuronectid flatfishes. The microsporidan Glugea stephani is a common parasite of juvenile English sole (Parophrys vetulus) in Yaquina Bay, Oregon. Field observations indicated that fish became infected only in the upper estuary where summer temperatures were above 15C and the incidence of infection reached 79.8% in the late fall. Laboratory infections developed and parasite growth occurred only at or above 15C. The parasite was successfully transmitted to juvenile English sole by brine shrimp (Artemia salina) and amphipod (Corophium spinocorne) vectors as well as by direct ingestion of spores by the host. Infections that resulted from ingestion of spore-carrying vectors were much heavier than those resulting from the direct ingestion of spores. The speckled sanddab (Citharichthys stigmaeus), a nonpleuronectid flatfish, and chum salmon (Oncorhynchus keta) were refractory to G. stephani infection in the laboratory."} {"id": "PMID:1271308", "title": "The cell surface of Trypanosoma musculi bloodstream forms. I. Fine structure and cytochemistry.", "content": "An extracellular surface coat was observed at the fine-structural level on the outer lamina of the pellicular and flagellar membranes of intact Trypanosoma musculi bloodstream forms. The surface coat had a mean width of 9.2 nm, and was composed of a somewhat electron dense, uneven, fibrillar-like matrix. Brief trypsin treatment of living blood forms completely removed the cell surface coat.", "contents": "The cell surface of Trypanosoma musculi bloodstream forms. I. Fine structure and cytochemistry. An extracellular surface coat was observed at the fine-structural level on the outer lamina of the pellicular and flagellar membranes of intact Trypanosoma musculi bloodstream forms. The surface coat had a mean width of 9.2 nm, and was composed of a somewhat electron dense, uneven, fibrillar-like matrix. Brief trypsin treatment of living blood forms completely removed the cell surface coat."} {"id": "PMID:1271309", "title": "Scanning electron microscope observations of Amoeba proteus during phagocytosis.", "content": "Phagocytosing Amoeba proteus at different stages of forming foodcups have been observed by scanning electron microscopy. A nonphagocytosing ameba is characterized by dorsal and lateral ridges running longitudinally over the posterior half of the cell and its attachment to the substrate over small areas. When stimulated by prey organisms, the ameba loses polarity and ridges, and adheres to the substrate more firmly over a wider area of contact. Then it forms broad pseudopods to surround its prey and this results in the formation of foodcups. The surface of all ameba is covered with small projections, and membranous blebs are often seen on the surface of phagocytosing organisms.", "contents": "Scanning electron microscope observations of Amoeba proteus during phagocytosis. Phagocytosing Amoeba proteus at different stages of forming foodcups have been observed by scanning electron microscopy. A nonphagocytosing ameba is characterized by dorsal and lateral ridges running longitudinally over the posterior half of the cell and its attachment to the substrate over small areas. When stimulated by prey organisms, the ameba loses polarity and ridges, and adheres to the substrate more firmly over a wider area of contact. Then it forms broad pseudopods to surround its prey and this results in the formation of foodcups. The surface of all ameba is covered with small projections, and membranous blebs are often seen on the surface of phagocytosing organisms."} {"id": "PMID:1271320", "title": "The health of clients of a social service department.", "content": "A survey was undertaken of the health problems and current medical care of new clients making contact with the Social Service Department of an outer London borough. The findings indicated that social-service clients represent a high-morbidity group of the population: 47 per cent of the survey sample showed evidence of major physical illness or disability, and 16 per cent of major mental illness. A sub-group was identified, corresponding to about 300 new clients annually, who suffered from serious ill-health or disability, but were at the time not under medical care.These findings support the argument for closer liaison between medical and social services in the community and, in particular, for more social-worker attachments in general practice.", "contents": "The health of clients of a social service department. A survey was undertaken of the health problems and current medical care of new clients making contact with the Social Service Department of an outer London borough. The findings indicated that social-service clients represent a high-morbidity group of the population: 47 per cent of the survey sample showed evidence of major physical illness or disability, and 16 per cent of major mental illness. A sub-group was identified, corresponding to about 300 new clients annually, who suffered from serious ill-health or disability, but were at the time not under medical care.These findings support the argument for closer liaison between medical and social services in the community and, in particular, for more social-worker attachments in general practice."} {"id": "PMID:1271321", "title": "Home deliveries in Holland. Dutch maternity care and home confinements.", "content": "In the Netherlands a majority of all deliveries take place at home. The perinatal mortality rate is better than that reported from the United ffiingdom, probably because obstetric care in hospital is more active and aggressive. Dutch midwives play an important role and the specially trained home helps are most successful. I believe that, provided case selection is rigorous, many women are best delivered at home.", "contents": "Home deliveries in Holland. Dutch maternity care and home confinements. In the Netherlands a majority of all deliveries take place at home. The perinatal mortality rate is better than that reported from the United ffiingdom, probably because obstetric care in hospital is more active and aggressive. Dutch midwives play an important role and the specially trained home helps are most successful. I believe that, provided case selection is rigorous, many women are best delivered at home."} {"id": "PMID:1271322", "title": "The provision of cottage hospital beds.", "content": "The existence of cottage hospital beds is historically determined rather than planned, and there is apparently no official ratio for the provision of such beds. A comparative study, in North-east Scotland, of populations with and without access to cottage hospital beds suggests that providing 1.5 beds per 1,000 population is a reasonable basis for future discussion and planning.", "contents": "The provision of cottage hospital beds. The existence of cottage hospital beds is historically determined rather than planned, and there is apparently no official ratio for the provision of such beds. A comparative study, in North-east Scotland, of populations with and without access to cottage hospital beds suggests that providing 1.5 beds per 1,000 population is a reasonable basis for future discussion and planning."} {"id": "PMID:1271323", "title": "General-practitioner maternity units.", "content": "A study of information available for monitoring care was made during 1974 in 46 general-practitioner maternity units in the South-west of England. The information available did not form an adequate basis for monitoring at area level. Although many deliveries take place in general-practitioner maternity units in the South-west, perinatal mortality rates are low. Transfer of babies to a consultant unit, after the delivery is, however, commoner than elsewhere in England and Wales.", "contents": "General-practitioner maternity units. A study of information available for monitoring care was made during 1974 in 46 general-practitioner maternity units in the South-west of England. The information available did not form an adequate basis for monitoring at area level. Although many deliveries take place in general-practitioner maternity units in the South-west, perinatal mortality rates are low. Transfer of babies to a consultant unit, after the delivery is, however, commoner than elsewhere in England and Wales."} {"id": "PMID:1271324", "title": "Common ground in general-practitioner and health-visitor training--an experimental course.", "content": "A residential course for 21 general-practitioner vocational trainees and student health visitors is described. The aim was to introduce the two groups of trainee professionals to each other in an attempt to modify attitudes, increase knowledge of each other's work, and induce a more positive approach towards teamwork in their ultimate careers. Both groups achieved an improvement by the end, and over half said they understood the others' role better", "contents": "Common ground in general-practitioner and health-visitor training--an experimental course. A residential course for 21 general-practitioner vocational trainees and student health visitors is described. The aim was to introduce the two groups of trainee professionals to each other in an attempt to modify attitudes, increase knowledge of each other's work, and induce a more positive approach towards teamwork in their ultimate careers. Both groups achieved an improvement by the end, and over half said they understood the others' role better"} {"id": "PMID:1271325", "title": "Converting medical records to A4 size in general practice.", "content": "A procedure for converting the medical record envelopes now used in general practice to an A4-sized record folder is described. The average time for conversion was 20.2 minutes per record and the cost, excluding filing equipment, averaged 41.6 pence for each record. The average cost to the practice was reduced to 16.4 pence per record by the reimbursement of 70 per cent of the clerk's salary from the local Family Practitioner Committee.", "contents": "Converting medical records to A4 size in general practice. A procedure for converting the medical record envelopes now used in general practice to an A4-sized record folder is described. The average time for conversion was 20.2 minutes per record and the cost, excluding filing equipment, averaged 41.6 pence for each record. The average cost to the practice was reduced to 16.4 pence per record by the reimbursement of 70 per cent of the clerk's salary from the local Family Practitioner Committee."} {"id": "PMID:1271326", "title": "The role of practice manager--changes in attitudes promoted by the Royal College of General Practitioners.", "content": "Because of the roles traditionally required of them, and because of the insularity of ancillary staff in general medical practice, many senior ancillary staff may not have been giving their doctors the most effective support of which they are capable. This is changing as a result of the change-promoting activities of the North of England Faculty of the Royal College of General Practitioners.A survey of ancillary staff and general practitioners in the North of England has shown that the Royal College of General Practitioners has assisted ancillary staff to a greater consensus of more progressive views about the emerging role of practice manager than is the case amongst general practitioners. The results also show that differences in the size of practices have determined whether or not a need for a practice manager is perceived.The focus of interest created by this faculty of the Royal College of General Practitioners has resulted in the formation of special interest groups of senior ancillary staff in the North of England. These groups form a valuable resource for exploration and innovation to discover more effective means of organising and managing general medical practice.", "contents": "The role of practice manager--changes in attitudes promoted by the Royal College of General Practitioners. Because of the roles traditionally required of them, and because of the insularity of ancillary staff in general medical practice, many senior ancillary staff may not have been giving their doctors the most effective support of which they are capable. This is changing as a result of the change-promoting activities of the North of England Faculty of the Royal College of General Practitioners.A survey of ancillary staff and general practitioners in the North of England has shown that the Royal College of General Practitioners has assisted ancillary staff to a greater consensus of more progressive views about the emerging role of practice manager than is the case amongst general practitioners. The results also show that differences in the size of practices have determined whether or not a need for a practice manager is perceived.The focus of interest created by this faculty of the Royal College of General Practitioners has resulted in the formation of special interest groups of senior ancillary staff in the North of England. These groups form a valuable resource for exploration and innovation to discover more effective means of organising and managing general medical practice."} {"id": "PMID:1271327", "title": "Reasons for referral to hospital.", "content": "In a study in North-east Scotland, nine out of ten patients had a \"medical\" reason for referral to hospital-in half it was the severity of their illness and in half the need for investigation or special treatment. One out of five patients was in need of intensive nursing care and one out of 20 patients had a social reason for admission to hospital. General practitioners with access to cottage hospital beds would choose to treat over one quarter of their own patients. The choice of hospital was influenced by the doctor's diagnostic certainty.", "contents": "Reasons for referral to hospital. In a study in North-east Scotland, nine out of ten patients had a \"medical\" reason for referral to hospital-in half it was the severity of their illness and in half the need for investigation or special treatment. One out of five patients was in need of intensive nursing care and one out of 20 patients had a social reason for admission to hospital. General practitioners with access to cottage hospital beds would choose to treat over one quarter of their own patients. The choice of hospital was influenced by the doctor's diagnostic certainty."} {"id": "PMID:1271328", "title": "Vasectomy--a review of 100 cases.", "content": "A limited free vasectomy service providing for the needs of a rural area, with the counselling and operation conducted by a specially trained general practitioner is reported. The development of vasectomy as a contraceptive measure and some practical aspects of technique are reviewed and some characteristics of 100 patients operated on are recorded.", "contents": "Vasectomy--a review of 100 cases. A limited free vasectomy service providing for the needs of a rural area, with the counselling and operation conducted by a specially trained general practitioner is reported. The development of vasectomy as a contraceptive measure and some practical aspects of technique are reviewed and some characteristics of 100 patients operated on are recorded."} {"id": "PMID:1271329", "title": "Fatal illness in general practice.", "content": "In an investigation of fatal illness during a 12-month period in a practice of 5,897 patients in Glasgow, 58 deaths (42 male, 16 female) were recorded. Malignant neoplasms and myocardial infarction in male patients of 50 years and over accounted for 27 (46.6 per per cent) of the deaths. Thirty (51.7 per cent) of the deaths took place in hospital. Fifteen (25.9 per cent) of the deaths were sudden. In patients dying in hospital of malignant, cardiac, and respiratory disease the duration of the terminal stay in hospital represented a small proportion of the total duration of the illness, the principal burden of their care falling upon their families and community resources.In an integrated health service much yet remains to be accomplished in co-ordinating the efforts of hospital and community teams in caring for the fatally ill patient.", "contents": "Fatal illness in general practice. In an investigation of fatal illness during a 12-month period in a practice of 5,897 patients in Glasgow, 58 deaths (42 male, 16 female) were recorded. Malignant neoplasms and myocardial infarction in male patients of 50 years and over accounted for 27 (46.6 per per cent) of the deaths. Thirty (51.7 per cent) of the deaths took place in hospital. Fifteen (25.9 per cent) of the deaths were sudden. In patients dying in hospital of malignant, cardiac, and respiratory disease the duration of the terminal stay in hospital represented a small proportion of the total duration of the illness, the principal burden of their care falling upon their families and community resources.In an integrated health service much yet remains to be accomplished in co-ordinating the efforts of hospital and community teams in caring for the fatally ill patient."} {"id": "PMID:1271330", "title": "Regulation of gonadotrophin secretion in rams from birth to sexual maturity. I. Plasma LH, FSH and testosterone levels.", "content": "Plasma LH, FSH and testosterone concentrations were measured by radioimmunoassays in male crossbred Merino/Corriedale sheep from birth to 45 weeks of age. FSH levels were 11 and 22 ng/ml at birth, increased to peak levels (mean value of 47 ng/ml) at 5 weeks and fluctuated between 25 and 35 ng/ml for the next 40 weeks. Similarly, LH (less than 0-5 ng/ml) and testosterone (less than 38 ng/100 ml) levels were low at birth and were significantly elevated by 5 weeks of age. LH values varied betwen 0-9 and 3-0 ng/ml for the next 30 weeks and then a secondary rise occurred reaching levels of 2-4 ng/ml by the 41st week after birth. Concentrations of LH subsequently fell to levels observed in adult rams. Testosterone levels rose gradually between the 5th and the 25th week, and then increased rapidly to values of 270-517 ng/100 ml by the 41st week after birth, a time coincident with the peak LH levels. Histological examination of testicular biopsies demonstrated that Sertoli cell maturation occurred 17-21 weeks after birth and was followed by activation of spermatogenesis leading to the presence of spermatozoa in the seminiferous epithelium by 39-42 weeks of age.", "contents": "Regulation of gonadotrophin secretion in rams from birth to sexual maturity. I. Plasma LH, FSH and testosterone levels. Plasma LH, FSH and testosterone concentrations were measured by radioimmunoassays in male crossbred Merino/Corriedale sheep from birth to 45 weeks of age. FSH levels were 11 and 22 ng/ml at birth, increased to peak levels (mean value of 47 ng/ml) at 5 weeks and fluctuated between 25 and 35 ng/ml for the next 40 weeks. Similarly, LH (less than 0-5 ng/ml) and testosterone (less than 38 ng/100 ml) levels were low at birth and were significantly elevated by 5 weeks of age. LH values varied betwen 0-9 and 3-0 ng/ml for the next 30 weeks and then a secondary rise occurred reaching levels of 2-4 ng/ml by the 41st week after birth. Concentrations of LH subsequently fell to levels observed in adult rams. Testosterone levels rose gradually between the 5th and the 25th week, and then increased rapidly to values of 270-517 ng/100 ml by the 41st week after birth, a time coincident with the peak LH levels. Histological examination of testicular biopsies demonstrated that Sertoli cell maturation occurred 17-21 weeks after birth and was followed by activation of spermatogenesis leading to the presence of spermatozoa in the seminiferous epithelium by 39-42 weeks of age."} {"id": "PMID:1271331", "title": "Effect of decidual tissue on the uterine production of prostaglandins in pseudopregnant rats.", "content": "The concentration of prostaglandin F (PGF) in uterine vein plasma of non-traumatized pseudopregnant rats and pseudopregnant rats with deciduomata were not significantly different from each other at any of the times of pseudopregnancy studied (Days 7, 10 and 12). There was a significant increase in PGF levels on Day 10 in both groups of pseudopregnant animals (P less than 0-05) compared to the Day 4 values, and PGE values were significantly greater on Day 10 in the decidual tissue-bearing rats (P less than 0-01). A slight but not significant elevation in PGE concentration was observed on Days 7 and 12 in rats with deciduomata, but there was no significant difference in the control rats on Days 4, 7, 10 or 12. The results indicate that the prolongation of pseudopregnancy in rats with deciduomata is not due to a decreased production of uterine PGs and lend support to the recent suggestion of a luteotrophic effect of decidual tissue in the rat.", "contents": "Effect of decidual tissue on the uterine production of prostaglandins in pseudopregnant rats. The concentration of prostaglandin F (PGF) in uterine vein plasma of non-traumatized pseudopregnant rats and pseudopregnant rats with deciduomata were not significantly different from each other at any of the times of pseudopregnancy studied (Days 7, 10 and 12). There was a significant increase in PGF levels on Day 10 in both groups of pseudopregnant animals (P less than 0-05) compared to the Day 4 values, and PGE values were significantly greater on Day 10 in the decidual tissue-bearing rats (P less than 0-01). A slight but not significant elevation in PGE concentration was observed on Days 7 and 12 in rats with deciduomata, but there was no significant difference in the control rats on Days 4, 7, 10 or 12. The results indicate that the prolongation of pseudopregnancy in rats with deciduomata is not due to a decreased production of uterine PGs and lend support to the recent suggestion of a luteotrophic effect of decidual tissue in the rat."} {"id": "PMID:1271332", "title": "A study of seasonally delayed puberty in the male hare, Lepus Europaeus.", "content": "The brown hare, Lepus europaeus, has a mating season which extends from January to September. Adult males exhibit pronounced seasonal changes in the reproductive tract which are associated with changes in LH secretion. Maximum plasma levels of immunoreactive LH occur between March and June and minimal levels in the autumn non-mating period from September to December; this seasonal cycle in gonadotrophin output is reflected by the appropriate changes in the secretion of testosterone from the testes and in the activity of the accessory sex glands. Juvenile animals reach puberty only during the adult mating season, and the age of puberty thus varies with the date of birth. Males born before May reach puberty and become fertile at 3 months of age, while those born from May to July grow to a mature body size during the autumn non-mating season but puberty is delayed for several months. Since some animals experiencing delayed puberty were found to have elevated plasma levels of LH and testosterone, it is concluded that puberty is not completely suppresed by the environmental effects of the autumn, but that the developmental process is prolonged, resulting in the juveniles being synchronized with the adults in their reproductive activity.", "contents": "A study of seasonally delayed puberty in the male hare, Lepus Europaeus. The brown hare, Lepus europaeus, has a mating season which extends from January to September. Adult males exhibit pronounced seasonal changes in the reproductive tract which are associated with changes in LH secretion. Maximum plasma levels of immunoreactive LH occur between March and June and minimal levels in the autumn non-mating period from September to December; this seasonal cycle in gonadotrophin output is reflected by the appropriate changes in the secretion of testosterone from the testes and in the activity of the accessory sex glands. Juvenile animals reach puberty only during the adult mating season, and the age of puberty thus varies with the date of birth. Males born before May reach puberty and become fertile at 3 months of age, while those born from May to July grow to a mature body size during the autumn non-mating season but puberty is delayed for several months. Since some animals experiencing delayed puberty were found to have elevated plasma levels of LH and testosterone, it is concluded that puberty is not completely suppresed by the environmental effects of the autumn, but that the developmental process is prolonged, resulting in the juveniles being synchronized with the adults in their reproductive activity."} {"id": "PMID:1271333", "title": "Peripheral plasma levels of oestradiol-17 beta and progesterone in the bitch during the oestrous cycle, in normal pregnancy and after dexamethasone treatment.", "content": "Plasma oestradiol-17 beta concentrations in Labradors increased during pro-oestrus to an average maximal concentration of of 79-7 +/- 10-9 (S.D.) pg/ml, and then fell rapidly. In 6/7 bitches the peak occurred within 1 day of oestrus. No consistent changes in plasma oestradiol levels were observed during pregnancy and at parturition and the values were similar to those in late anoestrus. Plasma progesterone levels did not increase markedly during pro-oestrus. At oestrus, progesterone values rose and maximal concentrations, which varied from about 20 to about 55 ng/ml, were reached within a few days of the oestradiol peak. Plasma progesterone decreased in late pregnancy and in one of the three bitches studied in detail low or undetectable levels were reached 10 days before parturition. In the other two bitches an abrupt decrease in progesterone occurred just before parturition. Dexamethasone treatment (2 X 5 mg daily for 10 days) from Day 30 of pregnancy resulted in intrauterine death and resorption of the fetuses in the two bitches studied. Treatment from about Day 45 resulted in the birth of dead fetuses at Days 55 and 59 of pregnancy. The changes in plasma oestradiol levels were very small. No changes in plasma progesterone levels were seen when dexamethasone was given in late pregnancy, but an accelerated decline occurred after treatment in mid-pregnancy.", "contents": "Peripheral plasma levels of oestradiol-17 beta and progesterone in the bitch during the oestrous cycle, in normal pregnancy and after dexamethasone treatment. Plasma oestradiol-17 beta concentrations in Labradors increased during pro-oestrus to an average maximal concentration of of 79-7 +/- 10-9 (S.D.) pg/ml, and then fell rapidly. In 6/7 bitches the peak occurred within 1 day of oestrus. No consistent changes in plasma oestradiol levels were observed during pregnancy and at parturition and the values were similar to those in late anoestrus. Plasma progesterone levels did not increase markedly during pro-oestrus. At oestrus, progesterone values rose and maximal concentrations, which varied from about 20 to about 55 ng/ml, were reached within a few days of the oestradiol peak. Plasma progesterone decreased in late pregnancy and in one of the three bitches studied in detail low or undetectable levels were reached 10 days before parturition. In the other two bitches an abrupt decrease in progesterone occurred just before parturition. Dexamethasone treatment (2 X 5 mg daily for 10 days) from Day 30 of pregnancy resulted in intrauterine death and resorption of the fetuses in the two bitches studied. Treatment from about Day 45 resulted in the birth of dead fetuses at Days 55 and 59 of pregnancy. The changes in plasma oestradiol levels were very small. No changes in plasma progesterone levels were seen when dexamethasone was given in late pregnancy, but an accelerated decline occurred after treatment in mid-pregnancy."} {"id": "PMID:1271334", "title": "Effect of ovarian sex hormones on the pool of free amino acids in maternal tissues of pregnant rats fed a protein-free diet.", "content": "The effects of s.c. injections of 5 mug oestrone/kg and 50 mg progesterone/kg on Days 5-7 of gestation were investigated in rats fed a protein-free diet. The decrease in essential and non-essential amino acid concentrations in maternal liver and the implantation site caused by dietary protein deficiency was restored to control values, whereas the alterations of the plasma free amino acid concentrations, except for arginine and glycine, were not reversed by hormone treatment.", "contents": "Effect of ovarian sex hormones on the pool of free amino acids in maternal tissues of pregnant rats fed a protein-free diet. The effects of s.c. injections of 5 mug oestrone/kg and 50 mg progesterone/kg on Days 5-7 of gestation were investigated in rats fed a protein-free diet. The decrease in essential and non-essential amino acid concentrations in maternal liver and the implantation site caused by dietary protein deficiency was restored to control values, whereas the alterations of the plasma free amino acid concentrations, except for arginine and glycine, were not reversed by hormone treatment."} {"id": "PMID:1271335", "title": "Steroid-protein interactions in bovine plasma.", "content": "The binding of testosterone, corticosterone and 17alpha-hydroxyprogesterone by bull plasma protein was studied by equilibrium dialysis. Testosterone in bovine plasma was bound by a CBG-like protein and by a specific protein (testosterone-binding protein or TBP) of limited capacity and high affinity. The TBP was specific for C18 and C19 steroids with a 17 beta-hydroxy group. Precision of the steroid-protein binding measurements was tested and was satisfactory. The testosterone-binding capacity in bull plasma samples did not seem to be related to testosterone levels in peripheral plasma. Significant differences between bulls and cows with regard to the binding capacity were observed.", "contents": "Steroid-protein interactions in bovine plasma. The binding of testosterone, corticosterone and 17alpha-hydroxyprogesterone by bull plasma protein was studied by equilibrium dialysis. Testosterone in bovine plasma was bound by a CBG-like protein and by a specific protein (testosterone-binding protein or TBP) of limited capacity and high affinity. The TBP was specific for C18 and C19 steroids with a 17 beta-hydroxy group. Precision of the steroid-protein binding measurements was tested and was satisfactory. The testosterone-binding capacity in bull plasma samples did not seem to be related to testosterone levels in peripheral plasma. Significant differences between bulls and cows with regard to the binding capacity were observed."} {"id": "PMID:1271336", "title": "Deep freezing of sheep embryos.", "content": "Sheep embryos, collected 1-8 days after oestrus, were placed in Dulbecco's phosphate-buffered saline medium (PBS). After treatment, the viability of the embryos was tested by temporary transfer to ligated rabbit oviducts. In Exp. 1, Days 5-8 embryos survived for at least 15 min at 0 degrees C in the presence of 1-5 M-DMSO. In Exp. 2, 12/14 Days 5-8 embryos survived after being frozen in 1-5 M-DMSO at 0-3 degrees C/min to temperatures ranging between-15 degrees and -60 degrees C and then thawed at 12 degrees C/min. In Exp. 3, Days 5-8 embryos were frozen in 1-5 M-DMSO at 0-3 degrees C/min to below-65 degrees C before being transferred to liquid nitrogen (-196 degrees C), and stored for 12 hr to 1 month. The embryos were thawed at 3 degrees C/min, 12 degrees C/MIN or 360 degrees C/min and, after transfer to rabbit oviducts, 0/4, 10/36 and 1/4, respectively, developed normally. The 11 embryos which were considered normal when recovered from the rabbit oviducts plus 1 slightly retarded embryo were transferred to 7 recipient ewes. Four ewes subsequently lambed, producing 5 lambs. In addition, 8 embryos were transferred to 4 ewes directly after thawing. Three of these ewes subsequently lambed, producing 3 lambs.", "contents": "Deep freezing of sheep embryos. Sheep embryos, collected 1-8 days after oestrus, were placed in Dulbecco's phosphate-buffered saline medium (PBS). After treatment, the viability of the embryos was tested by temporary transfer to ligated rabbit oviducts. In Exp. 1, Days 5-8 embryos survived for at least 15 min at 0 degrees C in the presence of 1-5 M-DMSO. In Exp. 2, 12/14 Days 5-8 embryos survived after being frozen in 1-5 M-DMSO at 0-3 degrees C/min to temperatures ranging between-15 degrees and -60 degrees C and then thawed at 12 degrees C/min. In Exp. 3, Days 5-8 embryos were frozen in 1-5 M-DMSO at 0-3 degrees C/min to below-65 degrees C before being transferred to liquid nitrogen (-196 degrees C), and stored for 12 hr to 1 month. The embryos were thawed at 3 degrees C/min, 12 degrees C/MIN or 360 degrees C/min and, after transfer to rabbit oviducts, 0/4, 10/36 and 1/4, respectively, developed normally. The 11 embryos which were considered normal when recovered from the rabbit oviducts plus 1 slightly retarded embryo were transferred to 7 recipient ewes. Four ewes subsequently lambed, producing 5 lambs. In addition, 8 embryos were transferred to 4 ewes directly after thawing. Three of these ewes subsequently lambed, producing 3 lambs."} {"id": "PMID:1271337", "title": "Comparison of neutral proteinase activities in cock and ram spermatozoa and observations on a proacrosin in cock spermatozoa.", "content": "Cock spermatozoa, like trypsin, induced a rapid fall in the viscosity of gelatin solutions but ram spermatozoa and inhibitor-free ram acrosin were ineffective. The gelatin-hydrolysing activity in cock spermatozoa was solubilized at pH 8 in the presence of calcium ions but comparable extracts of ram spermatozoa were inactive. Both extracts showed acrosin activity (assayed with benzoylarginine ethyl ester). The two catalytic activities of cock spermatozoa were each susceptible to the same trypsin inhibitors and during fractionations they were not separable. We deduce that cock acrosin, and probably some other avian acrosins, have the power to degrade dissolved gelatin while ram acrosin does not. The acrosin in cock spermatozoa, unlike that in ram spermatozoa, was inactivated at pH 2-7. Acid extracts of the former contain an inactive precursor of acrosin which undergoes spontaneous re-activation in buffers, pH 8, containing calcium ions. In this respect it resembles the proacrosin of rabbit testis.", "contents": "Comparison of neutral proteinase activities in cock and ram spermatozoa and observations on a proacrosin in cock spermatozoa. Cock spermatozoa, like trypsin, induced a rapid fall in the viscosity of gelatin solutions but ram spermatozoa and inhibitor-free ram acrosin were ineffective. The gelatin-hydrolysing activity in cock spermatozoa was solubilized at pH 8 in the presence of calcium ions but comparable extracts of ram spermatozoa were inactive. Both extracts showed acrosin activity (assayed with benzoylarginine ethyl ester). The two catalytic activities of cock spermatozoa were each susceptible to the same trypsin inhibitors and during fractionations they were not separable. We deduce that cock acrosin, and probably some other avian acrosins, have the power to degrade dissolved gelatin while ram acrosin does not. The acrosin in cock spermatozoa, unlike that in ram spermatozoa, was inactivated at pH 2-7. Acid extracts of the former contain an inactive precursor of acrosin which undergoes spontaneous re-activation in buffers, pH 8, containing calcium ions. In this respect it resembles the proacrosin of rabbit testis."} {"id": "PMID:1271338", "title": "The storage of cow eggs at room temperature and at low temperatures.", "content": "The survival and development of cow eggs in the rabbit oviduct after storage at room temperature and after cooling and storage at 0-7-5 degrees C was examined. In PBS medium at room temperature 88% of Day-5 and 85% of Day-3 eggs showed normal development, but in TCM 199, 71% of Day-5 and only 49% of Day-3 eggs showed normal development. Duration of storage (1 1/2-2 hr or 6 1/2-7 1/2 hr) and cleavage stage before storage had no appreciable effect on development. Some retardation of development occurred in Day-3 eggs after 96 hr in the rabbit oviduct when compared to Day-5 eggs after 48 hr. Cooling of Day-5 and Day-6 eggs to 0-7-5 degrees C resulted in degeneration of a large proportion of eggs. Of the factors examined, storage medium (PBS or PBS+20%FCS), storage time (2 min, 24 hr) and storage temperature (0, 2, 5 or 7-5 degrees C) had little effect, but slower cooling rates tended to improve survival of eggs although the differences were not significant. More morulae (greater than 32 cells) than 8-to 24-celled eggs developed normally.", "contents": "The storage of cow eggs at room temperature and at low temperatures. The survival and development of cow eggs in the rabbit oviduct after storage at room temperature and after cooling and storage at 0-7-5 degrees C was examined. In PBS medium at room temperature 88% of Day-5 and 85% of Day-3 eggs showed normal development, but in TCM 199, 71% of Day-5 and only 49% of Day-3 eggs showed normal development. Duration of storage (1 1/2-2 hr or 6 1/2-7 1/2 hr) and cleavage stage before storage had no appreciable effect on development. Some retardation of development occurred in Day-3 eggs after 96 hr in the rabbit oviduct when compared to Day-5 eggs after 48 hr. Cooling of Day-5 and Day-6 eggs to 0-7-5 degrees C resulted in degeneration of a large proportion of eggs. Of the factors examined, storage medium (PBS or PBS+20%FCS), storage time (2 min, 24 hr) and storage temperature (0, 2, 5 or 7-5 degrees C) had little effect, but slower cooling rates tended to improve survival of eggs although the differences were not significant. More morulae (greater than 32 cells) than 8-to 24-celled eggs developed normally."} {"id": "PMID:1271339", "title": "Effects of carnitine on oxygen uptake and utilization of (U-14C)palmitate by ejaculated bull spermatozoa.", "content": "Fatty acid oxidation by washed intact ejaculated bull spermatozoa was depressed by carnitine concentrations as low as 5 mM, whereas oxygen uptake was only depressed by concentrations of 20 mM or above. Incorporation of (U-14C)-palmitate into 1,2-diglycerides was stimulated, and there was some stimulation of incorporation into phospholipids.", "contents": "Effects of carnitine on oxygen uptake and utilization of (U-14C)palmitate by ejaculated bull spermatozoa. Fatty acid oxidation by washed intact ejaculated bull spermatozoa was depressed by carnitine concentrations as low as 5 mM, whereas oxygen uptake was only depressed by concentrations of 20 mM or above. Incorporation of (U-14C)-palmitate into 1,2-diglycerides was stimulated, and there was some stimulation of incorporation into phospholipids."} {"id": "PMID:1271340", "title": "Seasonal variations in the response of the testis and LH levels to hemicastration of adult rams.", "content": "The weight and histology of the testis and plasma LH levels were analysed after hemicastration of adult Ile-de-France rams in spring or in autumn. After hemicastration, the remaining testes were significantly heavier than those of entire animals measured at the same time of year. At 4 or 6 months after hemicastration performed in spring, the remaining testes were hypertrophied by nearly 40% as compared to the testes of entire sexually active animals, assessed in autumn. The variations of intertubular tissue volume, total seminiferous tubule length, stem cell stocks, daily production of round spermatids, and cellular volume of primary spermatocytes paralleled the variations in testis weight. The annual decrease of the area of the Sertoli cell nuclei and of the yield of meiosis and beginning of spermiogenesis during the non-breeding season was prevented by hemicastration performed in autumn. Plasma LH levels were consistently elevated till autumn after hemicastration performed in spring. A positive and significant correlation was observed between LH levels and yields of spermatogonial divisions.", "contents": "Seasonal variations in the response of the testis and LH levels to hemicastration of adult rams. The weight and histology of the testis and plasma LH levels were analysed after hemicastration of adult Ile-de-France rams in spring or in autumn. After hemicastration, the remaining testes were significantly heavier than those of entire animals measured at the same time of year. At 4 or 6 months after hemicastration performed in spring, the remaining testes were hypertrophied by nearly 40% as compared to the testes of entire sexually active animals, assessed in autumn. The variations of intertubular tissue volume, total seminiferous tubule length, stem cell stocks, daily production of round spermatids, and cellular volume of primary spermatocytes paralleled the variations in testis weight. The annual decrease of the area of the Sertoli cell nuclei and of the yield of meiosis and beginning of spermiogenesis during the non-breeding season was prevented by hemicastration performed in autumn. Plasma LH levels were consistently elevated till autumn after hemicastration performed in spring. A positive and significant correlation was observed between LH levels and yields of spermatogonial divisions."} {"id": "PMID:1271341", "title": "The effect of progesterone, oestradiol and HCG on cell-mediated immunity in pregnant mice.", "content": "During pregnancy in mice, cell-mediated immunity as measured by a contact allergic reaction to picryl chloride was diminished (P less than 0.001). Mice in which delay of implantation was maintained by progesterone, and mice with progesterone- and oestradiol-maintained pregnancies, also showed a reduction in the inflammatory response. The response of pseudopregnant mice did not differ from that of the non-pregnant controls. Young mice sensitized before complete immunological competence gave a 50% response. The response doubled in animals given a second sensitization. The extent of the response in females with delay of implantation varied inversely with the dose of progesterone. A range of oestrogen doses gave the same depression in the response when given to pseudopregnant animals. Administration of HCG to pseudopregnant mice also reduced the inflammatory response.", "contents": "The effect of progesterone, oestradiol and HCG on cell-mediated immunity in pregnant mice. During pregnancy in mice, cell-mediated immunity as measured by a contact allergic reaction to picryl chloride was diminished (P less than 0.001). Mice in which delay of implantation was maintained by progesterone, and mice with progesterone- and oestradiol-maintained pregnancies, also showed a reduction in the inflammatory response. The response of pseudopregnant mice did not differ from that of the non-pregnant controls. Young mice sensitized before complete immunological competence gave a 50% response. The response doubled in animals given a second sensitization. The extent of the response in females with delay of implantation varied inversely with the dose of progesterone. A range of oestrogen doses gave the same depression in the response when given to pseudopregnant animals. Administration of HCG to pseudopregnant mice also reduced the inflammatory response."} {"id": "PMID:1271351", "title": "The action of D2O on the motility of human spermatozoa.", "content": "The effect of 25%, 50%, 75% and 100% D2O on the survival of human spermatozoa was investigated. More spermatozoa were affected and died more quickly as the concentration of D2O increased. Spermatozoa died instantly in 100% D2O.", "contents": "The action of D2O on the motility of human spermatozoa. The effect of 25%, 50%, 75% and 100% D2O on the survival of human spermatozoa was investigated. More spermatozoa were affected and died more quickly as the concentration of D2O increased. Spermatozoa died instantly in 100% D2O."} {"id": "PMID:1271352", "title": "Artificial insemination with spermatozoa in formaldehyde.", "content": "The ability of formaldehyde to preserve the integrity of the membranes of spermatozoa, as indicated by eosin staining (Dott & Foster, 1975), prompted an investigation to discover what other properties of spermatozoa were preserved by low concentrations of formaldehyde in vitro. In a series of experiments on bull, ram and boar spermatozoa it has been shown that spermatozoa rendered immotile by formaldehyde recovered their motility when the formaldehyde was removed by washing up to 12 hr afterwards (H.M. Dott & G.C. Foster, unpublished). To find out if fertility was preserved ewes and sows were inseminated with spermatozoa rendered immotile with formaldehyde.", "contents": "Artificial insemination with spermatozoa in formaldehyde. The ability of formaldehyde to preserve the integrity of the membranes of spermatozoa, as indicated by eosin staining (Dott & Foster, 1975), prompted an investigation to discover what other properties of spermatozoa were preserved by low concentrations of formaldehyde in vitro. In a series of experiments on bull, ram and boar spermatozoa it has been shown that spermatozoa rendered immotile by formaldehyde recovered their motility when the formaldehyde was removed by washing up to 12 hr afterwards (H.M. Dott & G.C. Foster, unpublished). To find out if fertility was preserved ewes and sows were inseminated with spermatozoa rendered immotile with formaldehyde."} {"id": "PMID:1271353", "title": "Changes in the composition of the excurrent duct system of the rat testis during postnatal development.", "content": "The gross composition of the testicular excurrent duct system of the rat was examined and compared along the length of the duct and with samples of testis, bladder and liver. Changes in composition with age were examined by analysing tissue from animals at postnatal ages of 19, 36, 48, 60, 90 and 120 days. In adult animals, testicular tissue was characterized by having the lowest dry weight, accompanied by low levels of total protein, lipid, RNA and glycogen; DNA, phospholipids and sialic acid were at levels similar to other tissues. A high proportion of the total protein was soluble. The ductuli efferentes plus initial segment of the epididymis were characterized by high levels of total lipid. The caput epididymidis contained a low level of total protein but a high level of acid-soluble phosphorus. The cauda epididymidis had a low dry weight and low levels of total protein, soluble protein, and lipid, but high levels of acid-soluble phosphorus, DNA and sialic acid. The ductus deferens contained small amounts of RNA and DNA but had a high dry weight, high total protein, soluble protein and glycogen. Several trends were apparent with increasing age. Dry weight increased in the ductuli efferentes plus initial segment, whilst total protein decreased in the caput and cauda epididymidis. Total lipid increased in the ductuli efferentes plus initial segment and acid-soluble phosphorus and sialic acid increased in all other segments of the excurrent duct system. In all segments the content of RNA and DNA decreased as the animals matured. The concentration of calcium and magnesium in the excurrent duct system was not significantly different from those levels found in the liver. High levels of spermine and spermidine were confirmed in the prostate, and were also detected in the testis, caput epididymidis and cauda epididymidis, but at a much lower concentration.", "contents": "Changes in the composition of the excurrent duct system of the rat testis during postnatal development. The gross composition of the testicular excurrent duct system of the rat was examined and compared along the length of the duct and with samples of testis, bladder and liver. Changes in composition with age were examined by analysing tissue from animals at postnatal ages of 19, 36, 48, 60, 90 and 120 days. In adult animals, testicular tissue was characterized by having the lowest dry weight, accompanied by low levels of total protein, lipid, RNA and glycogen; DNA, phospholipids and sialic acid were at levels similar to other tissues. A high proportion of the total protein was soluble. The ductuli efferentes plus initial segment of the epididymis were characterized by high levels of total lipid. The caput epididymidis contained a low level of total protein but a high level of acid-soluble phosphorus. The cauda epididymidis had a low dry weight and low levels of total protein, soluble protein, and lipid, but high levels of acid-soluble phosphorus, DNA and sialic acid. The ductus deferens contained small amounts of RNA and DNA but had a high dry weight, high total protein, soluble protein and glycogen. Several trends were apparent with increasing age. Dry weight increased in the ductuli efferentes plus initial segment, whilst total protein decreased in the caput and cauda epididymidis. Total lipid increased in the ductuli efferentes plus initial segment and acid-soluble phosphorus and sialic acid increased in all other segments of the excurrent duct system. In all segments the content of RNA and DNA decreased as the animals matured. The concentration of calcium and magnesium in the excurrent duct system was not significantly different from those levels found in the liver. High levels of spermine and spermidine were confirmed in the prostate, and were also detected in the testis, caput epididymidis and cauda epididymidis, but at a much lower concentration."} {"id": "PMID:1271354", "title": "Follicular atresia in the infant human ovary.", "content": "The pattern of follicular atresia was studied in nine ovaries from children between the ages 3 months and 8 years. Atretic follicles were found among follicles at all stages of development. The percentage of follicles with signs of atresia became larger as the size of the follicles increased. Only 2% of small follicles (Type 3b) showed signs of atresia, while all follicles greater than 1 mm in diameter (Type 8) were atretic. In follicles of Type 5 and larger, four stages of atresia, which represent consecutive stages of a single atretic process, were defined. The beginning of atresia was characterized by the presence of pyknotic granulosa cells. As atresia progressed, the granulosa layer disappeared, the oocyte became necrotic, the follicle collapsed and the theca cells became hypertrophied. The oocyte can degenerate in several ways: it can be penetrated by cells, the nucleus can become pyknotic or it may complete meiotic prophase. It is suggested that the last event is only possible after the oocyte has reached its full size and has completed RNA synthesis.", "contents": "Follicular atresia in the infant human ovary. The pattern of follicular atresia was studied in nine ovaries from children between the ages 3 months and 8 years. Atretic follicles were found among follicles at all stages of development. The percentage of follicles with signs of atresia became larger as the size of the follicles increased. Only 2% of small follicles (Type 3b) showed signs of atresia, while all follicles greater than 1 mm in diameter (Type 8) were atretic. In follicles of Type 5 and larger, four stages of atresia, which represent consecutive stages of a single atretic process, were defined. The beginning of atresia was characterized by the presence of pyknotic granulosa cells. As atresia progressed, the granulosa layer disappeared, the oocyte became necrotic, the follicle collapsed and the theca cells became hypertrophied. The oocyte can degenerate in several ways: it can be penetrated by cells, the nucleus can become pyknotic or it may complete meiotic prophase. It is suggested that the last event is only possible after the oocyte has reached its full size and has completed RNA synthesis."} {"id": "PMID:1271355", "title": "Preliminary results on plasma progesterone levels during pregnancy and superfetation in the hare, Lepus Europaeus.", "content": "Peripheral plasma progesterone levels were studied in pregnant hares. A rise occurred at the beginning of pregnancy, followed by a plateau from Days 10 to 35, and then a drop during the days just before parturition. No significant differences were noted between progesterone levels in pregnancies initiated at the pre-partum oestrus and those from other oestrous periods.", "contents": "Preliminary results on plasma progesterone levels during pregnancy and superfetation in the hare, Lepus Europaeus. Peripheral plasma progesterone levels were studied in pregnant hares. A rise occurred at the beginning of pregnancy, followed by a plateau from Days 10 to 35, and then a drop during the days just before parturition. No significant differences were noted between progesterone levels in pregnancies initiated at the pre-partum oestrus and those from other oestrous periods."} {"id": "PMID:1271356", "title": "The binding of labelled basic proteins by boar spermatozoa.", "content": "Seminal plasma basic proteins were labelled with 131I. The efficiency of the labelling was studied by superimposing protein density traces on a radioactive fractionation plot. These labelled proteins were incubated with spermatozoa and shown to bind more readily to spermatozoa from boars after the removal of the vesicular glands than to spermatozoa obtained from their normal litter mates. Most of the labelled protein became bound to the membranes which were isolated by sucrose density gradient centrifugation. The membranes were separated into two bands which equilibrated at the relative densities of 1-150 and 1-165. These fractions consisted of membrane vesicles of different size; the smaller band on the gradient, which equilibrated at 1-165, consisted of denser membrane material.", "contents": "The binding of labelled basic proteins by boar spermatozoa. Seminal plasma basic proteins were labelled with 131I. The efficiency of the labelling was studied by superimposing protein density traces on a radioactive fractionation plot. These labelled proteins were incubated with spermatozoa and shown to bind more readily to spermatozoa from boars after the removal of the vesicular glands than to spermatozoa obtained from their normal litter mates. Most of the labelled protein became bound to the membranes which were isolated by sucrose density gradient centrifugation. The membranes were separated into two bands which equilibrated at the relative densities of 1-150 and 1-165. These fractions consisted of membrane vesicles of different size; the smaller band on the gradient, which equilibrated at 1-165, consisted of denser membrane material."} {"id": "PMID:1271365", "title": "Anomalous litters in hybrid mice and the retention of spermatozoa in the female tract.", "content": "Suspected superfetation was investigated in a Glasgow hybrid stock of mice. The male was removed either (i) a few days before parturition, or (ii) immediately after mating and on 23 and 25 occasions, respectively, a second litter was born. Members of the anomalous litters were inbred for 10 generations, but the incidence of supernumerary litters did not increase beyond 2-5%. The anterior part of over 500 reproductive tracts, at various stages of pregnancy and after parturition, were serially sectioned but a second set of embryos was not found. The second gestation was of normal length and superfetation was not therefore considered to be the cause of the anomalous litters. In two females, one non-pregnant and one pregnant, spermatozoa were found in the uterus and oviducts 8 days after mating and in distended uterine glands 15 days after mating respectively. It is concluded that the anomalous litters were derived from the fertilization of eggs ovulated at the post-partum oestrus by spermatozoa which had been retained in the female tract for at least 23 days.", "contents": "Anomalous litters in hybrid mice and the retention of spermatozoa in the female tract. Suspected superfetation was investigated in a Glasgow hybrid stock of mice. The male was removed either (i) a few days before parturition, or (ii) immediately after mating and on 23 and 25 occasions, respectively, a second litter was born. Members of the anomalous litters were inbred for 10 generations, but the incidence of supernumerary litters did not increase beyond 2-5%. The anterior part of over 500 reproductive tracts, at various stages of pregnancy and after parturition, were serially sectioned but a second set of embryos was not found. The second gestation was of normal length and superfetation was not therefore considered to be the cause of the anomalous litters. In two females, one non-pregnant and one pregnant, spermatozoa were found in the uterus and oviducts 8 days after mating and in distended uterine glands 15 days after mating respectively. It is concluded that the anomalous litters were derived from the fertilization of eggs ovulated at the post-partum oestrus by spermatozoa which had been retained in the female tract for at least 23 days."} {"id": "PMID:1271371", "title": "The role of oestrogen in the control of ciliated cells of the human endometrium.", "content": "The incidence of ciliated cells in the human endometrium was determined. Conditions associated with an excess of oestrogenic activity were characterized by an increased incidence of ciliated cells, whilst oestrogen deficiency was associated with decreased numbers. When endometrium was cultured, addition of oestradiol-17 beta caused an increase in the ciliated cell population.", "contents": "The role of oestrogen in the control of ciliated cells of the human endometrium. The incidence of ciliated cells in the human endometrium was determined. Conditions associated with an excess of oestrogenic activity were characterized by an increased incidence of ciliated cells, whilst oestrogen deficiency was associated with decreased numbers. When endometrium was cultured, addition of oestradiol-17 beta caused an increase in the ciliated cell population."} {"id": "PMID:1271372", "title": "Seminal plasma proteins and the reaction of spermatozoa from intact boars and from boars without seminal vesicles to cooling.", "content": "Spermatozoa from intact boars and from boars without seminal vesicles were resuspected in diluent and cooled at different rates to 0 degrees C. Glutamic oxaloacetic transaminase and lactate dehydrogenase activities were greater in the diluents which had contained spermatozoa from intact boars than in those which contained spermatozoa from animals without seminal vesicles. The incubation of seminal plasma from an intact boar with spermatozoa from a vesiculectomized animal before cooling also increased the enzyme activity in the diluent. The factors responsible for this effect were associated with the basic protein fractions of boar seminal plasma, in particular the proteins with haemagglutinating activity which may have been adsorbed onto the spermatozoa. Spermatozoa were exposed to colloidal Fe(OH)2+ to determine by electron microscopy the charge on the surface of the plasma membrane of washed epididymal spermatozoa and ejaculated spermatozoa from intact and vesiculectomized boars. Epididymal spermatozoa bound the positively charged particles more readily than the ejaculated spermatozoa from the intact boars, due to the absence of membrane-bound protein.", "contents": "Seminal plasma proteins and the reaction of spermatozoa from intact boars and from boars without seminal vesicles to cooling. Spermatozoa from intact boars and from boars without seminal vesicles were resuspected in diluent and cooled at different rates to 0 degrees C. Glutamic oxaloacetic transaminase and lactate dehydrogenase activities were greater in the diluents which had contained spermatozoa from intact boars than in those which contained spermatozoa from animals without seminal vesicles. The incubation of seminal plasma from an intact boar with spermatozoa from a vesiculectomized animal before cooling also increased the enzyme activity in the diluent. The factors responsible for this effect were associated with the basic protein fractions of boar seminal plasma, in particular the proteins with haemagglutinating activity which may have been adsorbed onto the spermatozoa. Spermatozoa were exposed to colloidal Fe(OH)2+ to determine by electron microscopy the charge on the surface of the plasma membrane of washed epididymal spermatozoa and ejaculated spermatozoa from intact and vesiculectomized boars. Epididymal spermatozoa bound the positively charged particles more readily than the ejaculated spermatozoa from the intact boars, due to the absence of membrane-bound protein."} {"id": "PMID:1271373", "title": "Fine structural changes in the epididymal epithelium of moles (Talpa europaea) throughout the year.", "content": "The epididymis of the European mole (Talpa europaea) was studied by light and electron microscopy. In the sexually active animal, spermatozoa mature during their passage through the epididymis and the structure of the cells lining the duct suggests a clear regional division into initial, middle and terminal segments. Numerous intra-epithelial vesicles were present in the distal part of the middle segment of sexually active moles and the lining epithelium in the terminal segment appeared to be secretory. Variation in the sensitivity of different regions of the epididymis to androgens was apparent: the principal cells of the initial segment were morphologically active only during the peak of the breeding season in spring, while the cells of the terminal segment became active earlier and remained so for longer. During sexual regression, many autophagic vacuoles were found in the principal cells, and these became transformed into lipofuscin pigment granules. Cells heavily laden with these granules appeared concurrently in the lining epithelium. It is suggested that such cells may be involved in the regression of principal cells by means of heterophagic activity. A similar situation was also observed, but to a lesser extent, at the beginning of the breeding season. Outside the breeding season, the organelles of the principal cells were poorly developed throughout the epididymis, and lipofuscin pigment granules remained in the principal and basal cells of adults. Such granules were seldom seen in immature animals.", "contents": "Fine structural changes in the epididymal epithelium of moles (Talpa europaea) throughout the year. The epididymis of the European mole (Talpa europaea) was studied by light and electron microscopy. In the sexually active animal, spermatozoa mature during their passage through the epididymis and the structure of the cells lining the duct suggests a clear regional division into initial, middle and terminal segments. Numerous intra-epithelial vesicles were present in the distal part of the middle segment of sexually active moles and the lining epithelium in the terminal segment appeared to be secretory. Variation in the sensitivity of different regions of the epididymis to androgens was apparent: the principal cells of the initial segment were morphologically active only during the peak of the breeding season in spring, while the cells of the terminal segment became active earlier and remained so for longer. During sexual regression, many autophagic vacuoles were found in the principal cells, and these became transformed into lipofuscin pigment granules. Cells heavily laden with these granules appeared concurrently in the lining epithelium. It is suggested that such cells may be involved in the regression of principal cells by means of heterophagic activity. A similar situation was also observed, but to a lesser extent, at the beginning of the breeding season. Outside the breeding season, the organelles of the principal cells were poorly developed throughout the epididymis, and lipofuscin pigment granules remained in the principal and basal cells of adults. Such granules were seldom seen in immature animals."} {"id": "PMID:1271374", "title": "Development of gonadotrophin-binding sites in the immature rat ovary.", "content": "There was a temporal relationship between ovarian development and the sites to which 125I-labelled gonadotrophins became bound. Labelled human LH and FSH bound uniformly to 5- and 15-day-old ovaries. At 21 days, heavy FSH and light LH binding was observed over the granulosa cells increased at Day 33 and again at Day 38. Quantitative determination by gamma-ray spectrophotometry of binding to ovarian sections showed that LH binding gradually increased with advancing age, but FSH binding remained relatively constant between Days 5 and 33 with a significant increase between Days 33 and 38.", "contents": "Development of gonadotrophin-binding sites in the immature rat ovary. There was a temporal relationship between ovarian development and the sites to which 125I-labelled gonadotrophins became bound. Labelled human LH and FSH bound uniformly to 5- and 15-day-old ovaries. At 21 days, heavy FSH and light LH binding was observed over the granulosa cells increased at Day 33 and again at Day 38. Quantitative determination by gamma-ray spectrophotometry of binding to ovarian sections showed that LH binding gradually increased with advancing age, but FSH binding remained relatively constant between Days 5 and 33 with a significant increase between Days 33 and 38."} {"id": "PMID:1271375", "title": "Hormonal control of pinocytosis in the uterine epithelium of the rat.", "content": "Ovariectomized rats were treated with oestradiol-17 beta and/or progesterone to mimic the hormonal parameters inducing uterine sensitivity for implantation. The degree of pinocytosis of trypan blue and ferritin in the endometrial cells was examined. Significant epithelial pinocytosis of trypan blue occurred after a 3-day treatment of progesterone, and uptake was independently increased by priming with oestrogen and by oestradiol given on the 3rd day of progesterone treatment. Progesterone treatment caused uptake of ferritin by the epithelial cells; in control animals epithelial and stromal cells were involved. Oestrogen priming enhanced ferritin absorption, while 'nidatory' oestrogen had no effect. Oestradiol given alone completely blocked pinocytosis of both intraluminally injected substances.", "contents": "Hormonal control of pinocytosis in the uterine epithelium of the rat. Ovariectomized rats were treated with oestradiol-17 beta and/or progesterone to mimic the hormonal parameters inducing uterine sensitivity for implantation. The degree of pinocytosis of trypan blue and ferritin in the endometrial cells was examined. Significant epithelial pinocytosis of trypan blue occurred after a 3-day treatment of progesterone, and uptake was independently increased by priming with oestrogen and by oestradiol given on the 3rd day of progesterone treatment. Progesterone treatment caused uptake of ferritin by the epithelial cells; in control animals epithelial and stromal cells were involved. Oestrogen priming enhanced ferritin absorption, while 'nidatory' oestrogen had no effect. Oestradiol given alone completely blocked pinocytosis of both intraluminally injected substances."} {"id": "PMID:1271377", "title": "Gonadotrophin-induced changes in the Sertoli cells of the immature mouse testis.", "content": "Highly purified preparations of human pituitary gonadotrophins were administered to immature male mice daily for 3 days. The mice were killed on the 9th day after birth and the testes were prepared for electron microscopy. FSH treatment caused an increase in the mass of Sertoli cell cytoplasm, and FSH and LH increased the size of mitochondria in these cells. The number of polysomes in each Sertoli cell was increased after FSH treatment, but the number of ribosomes/polysome was not affected.", "contents": "Gonadotrophin-induced changes in the Sertoli cells of the immature mouse testis. Highly purified preparations of human pituitary gonadotrophins were administered to immature male mice daily for 3 days. The mice were killed on the 9th day after birth and the testes were prepared for electron microscopy. FSH treatment caused an increase in the mass of Sertoli cell cytoplasm, and FSH and LH increased the size of mitochondria in these cells. The number of polysomes in each Sertoli cell was increased after FSH treatment, but the number of ribosomes/polysome was not affected."} {"id": "PMID:1271380", "title": "Inhibition of human sperm acrosin by synthetic agents.", "content": "Twenty-two synthetic proteinase inhibitors were tested for their inhibitory properties towards human acrosin. p-Nitrophenyl-p1-guanidino benzoate (NPGB) was the most effective (K1 value of 1-5 X 10(-8) M), producing a non-competitive type of inhibition in contrast to all other inhibitors which showed a competitive type of inhibition. The Michaelis constant for human acrosin on BAEE at pH 8-1 was calculated to be 4-25 X 10(-5) M.", "contents": "Inhibition of human sperm acrosin by synthetic agents. Twenty-two synthetic proteinase inhibitors were tested for their inhibitory properties towards human acrosin. p-Nitrophenyl-p1-guanidino benzoate (NPGB) was the most effective (K1 value of 1-5 X 10(-8) M), producing a non-competitive type of inhibition in contrast to all other inhibitors which showed a competitive type of inhibition. The Michaelis constant for human acrosin on BAEE at pH 8-1 was calculated to be 4-25 X 10(-5) M."} {"id": "PMID:1271386", "title": "HL-A antigens in Behcet's disease.", "content": "Twenty-six patients with Behcet's disease had complete HL-A typing. No patient had an HL-A antigen in significant excess. No patient had an HL-A antigen in significant excess. Only two patients had the B27 antigen: both patients had uveitis, but eight others who also had uveitis were B27 negative. No patient had ankylosing spondylitis or sacroilitis. Behcet's disease, although bearing some clinical resemblances to diseases related to the B27 antigen, i.e. ankylosing spondylitis and Reiter's syndrome, differs from them through the absence of spondylitis and because the association with B27, if it exists, is far weaker than that in ankylosing spondylitis or Reiter's disease.", "contents": "HL-A antigens in Behcet's disease. Twenty-six patients with Behcet's disease had complete HL-A typing. No patient had an HL-A antigen in significant excess. No patient had an HL-A antigen in significant excess. Only two patients had the B27 antigen: both patients had uveitis, but eight others who also had uveitis were B27 negative. No patient had ankylosing spondylitis or sacroilitis. Behcet's disease, although bearing some clinical resemblances to diseases related to the B27 antigen, i.e. ankylosing spondylitis and Reiter's syndrome, differs from them through the absence of spondylitis and because the association with B27, if it exists, is far weaker than that in ankylosing spondylitis or Reiter's disease."} {"id": "PMID:1271387", "title": "Bleeding, salicylates, and prolonged prothrombin time: three case reports and a review of the literature.", "content": "Fourteen cases of ASA induced hypoprothrombinemic bleeding, including three patients reported by the authors, are reviewed. Predisposing factors toward bleeding include malnutrition and malabsorption syndrome. Although the bleeding is usually benign, it may be serious on occasion. The importance of this rarely considered cause of ASA associated bleeding lies in the fact that it is readily corrected with Vitamin K.", "contents": "Bleeding, salicylates, and prolonged prothrombin time: three case reports and a review of the literature. Fourteen cases of ASA induced hypoprothrombinemic bleeding, including three patients reported by the authors, are reviewed. Predisposing factors toward bleeding include malnutrition and malabsorption syndrome. Although the bleeding is usually benign, it may be serious on occasion. The importance of this rarely considered cause of ASA associated bleeding lies in the fact that it is readily corrected with Vitamin K."} {"id": "PMID:1271388", "title": "Liver dysfunction and polymyalgia rheumatica. A case report.", "content": "Hepatic dysfunction may be a manifestation of polymyalgia rheumatica. We present a second patient with the polymyalgia rheumatica syndrome and a significantly elevated alkaline phosphtase who, on liver biopsy, demonstrated granuloma formation and massive infiltration of the portal spaces with lymphocytes. The alkaline phosphatase elevation was favorably influenced by low dose steroid therapy.", "contents": "Liver dysfunction and polymyalgia rheumatica. A case report. Hepatic dysfunction may be a manifestation of polymyalgia rheumatica. We present a second patient with the polymyalgia rheumatica syndrome and a significantly elevated alkaline phosphtase who, on liver biopsy, demonstrated granuloma formation and massive infiltration of the portal spaces with lymphocytes. The alkaline phosphatase elevation was favorably influenced by low dose steroid therapy."} {"id": "PMID:1271389", "title": "Experimental inflammation induced by naturally occurring microcrystalline calcium salts.", "content": "Inflammation caused by insoluble microcrystalline calcium salts was compared with inflammation elicited by soluble carrageenan and monosodium urate crystals, in rats' paws. Local and systemic responses to four calcium crystals, viz. pyrophosphate, triphosphate, oxalate, and tartrate were studied. Changes in liver function, reflected in reduced serum albumin and increased sleep times in response to barbiturates, indicative of systemic inflammation, occurred despite the localized nature of the crystal induced inflammation. Serum thiol levels were also reduced. These altered functions were similar to, but less pronounced than, those accompanying the severe systemic inflammation produced by Freund's adjuvant. A copper glycine complex was effective in reducing foot swelling due to triphosphate, and edema due to oxalate. Colchicine had very little effect on the inflammation caused by the insoluble calcium salts but inhibited inflammation due to sodium urats crystals and soluble carrageenan. Crystal-induced inflammation that is outwardly localized may induce biochemical changes that are similar to changes found in systemic inflammation.", "contents": "Experimental inflammation induced by naturally occurring microcrystalline calcium salts. Inflammation caused by insoluble microcrystalline calcium salts was compared with inflammation elicited by soluble carrageenan and monosodium urate crystals, in rats' paws. Local and systemic responses to four calcium crystals, viz. pyrophosphate, triphosphate, oxalate, and tartrate were studied. Changes in liver function, reflected in reduced serum albumin and increased sleep times in response to barbiturates, indicative of systemic inflammation, occurred despite the localized nature of the crystal induced inflammation. Serum thiol levels were also reduced. These altered functions were similar to, but less pronounced than, those accompanying the severe systemic inflammation produced by Freund's adjuvant. A copper glycine complex was effective in reducing foot swelling due to triphosphate, and edema due to oxalate. Colchicine had very little effect on the inflammation caused by the insoluble calcium salts but inhibited inflammation due to sodium urats crystals and soluble carrageenan. Crystal-induced inflammation that is outwardly localized may induce biochemical changes that are similar to changes found in systemic inflammation."} {"id": "PMID:1271390", "title": "Abnormal esophageal motility in primary Sj\u00f6gren's syndrome.", "content": "Esophageal monometric studies were done in 10 unselected patients with Sj\u00f6gren's syndrome, not associated with other connective tissue or chronic active hepatic disease. Nine of the patients revealed abnormal esophageal motility, consisting of absent or decreased contractility in the upper third of the esophagus. In four patients, the dysfunction also extended to other portions of the organ. Dryness of the mouth and oropharynx, or mucosal atrophy, does not explain these findings. The uniform pattern of the esophageal dysfunction found in patients with primary Sj\u00f6gren's syndrome, which differs from the patterns of involvement observed in other connective tissue diseases, suggests that primary Sj\u00f6gren's syndrome is probably a distinct entity.", "contents": "Abnormal esophageal motility in primary Sj\u00f6gren's syndrome. Esophageal monometric studies were done in 10 unselected patients with Sj\u00f6gren's syndrome, not associated with other connective tissue or chronic active hepatic disease. Nine of the patients revealed abnormal esophageal motility, consisting of absent or decreased contractility in the upper third of the esophagus. In four patients, the dysfunction also extended to other portions of the organ. Dryness of the mouth and oropharynx, or mucosal atrophy, does not explain these findings. The uniform pattern of the esophageal dysfunction found in patients with primary Sj\u00f6gren's syndrome, which differs from the patterns of involvement observed in other connective tissue diseases, suggests that primary Sj\u00f6gren's syndrome is probably a distinct entity."} {"id": "PMID:1271391", "title": "Pseudotumor of temporomandibular joint: destructive calcium pyrophosphate dihydrate arthropathy.", "content": "The clinical and pathological features of a tumor of the temporamandibular joint occurring in a 55 year old man, and subsequently identified as a calcium pyrophosphate dihydrate (CPPD) arthropathy, are reported. Crystalline deposits were identified by compensated light microscopy and confirmed with X-ray diffraction, transmission, and scanning electron microscopy. The relationship of this unique case to other clinical presentations of CPPD deposition disease and the implications of the histological features to the pathogenesis of pseudogout are discussed. This case demonstrates that CPPD arthropathy should be included in the differential diagnosis of an arthrosis or of a tumor involving the temporomandibular joint.", "contents": "Pseudotumor of temporomandibular joint: destructive calcium pyrophosphate dihydrate arthropathy. The clinical and pathological features of a tumor of the temporamandibular joint occurring in a 55 year old man, and subsequently identified as a calcium pyrophosphate dihydrate (CPPD) arthropathy, are reported. Crystalline deposits were identified by compensated light microscopy and confirmed with X-ray diffraction, transmission, and scanning electron microscopy. The relationship of this unique case to other clinical presentations of CPPD deposition disease and the implications of the histological features to the pathogenesis of pseudogout are discussed. This case demonstrates that CPPD arthropathy should be included in the differential diagnosis of an arthrosis or of a tumor involving the temporomandibular joint."} {"id": "PMID:1271392", "title": "Multiple vacuum discs, and early sign of ochronosis. Radiologic findings in two brothers.", "content": "Two brothers with ochronosis are reported and the radiological features of ochronotic vertebral disease are reviewed. A striking feature was the presence of multiple vacuum discs. This \"vacuum phenomenon\" constitutes one of the earliest radiologic changes in the spine and presumably represents areas of severe degeneration within the intervertebral discs. Other features included a dark pigmentation of the urine after standing or following the addition of sodium hydroxide, and calcification within the cartilages of the ears and intervertebral discs. There was no abnormality of the peripheral joints and pigmentary deposits in the ears, sclerae, or skin were not observed.", "contents": "Multiple vacuum discs, and early sign of ochronosis. Radiologic findings in two brothers. Two brothers with ochronosis are reported and the radiological features of ochronotic vertebral disease are reviewed. A striking feature was the presence of multiple vacuum discs. This \"vacuum phenomenon\" constitutes one of the earliest radiologic changes in the spine and presumably represents areas of severe degeneration within the intervertebral discs. Other features included a dark pigmentation of the urine after standing or following the addition of sodium hydroxide, and calcification within the cartilages of the ears and intervertebral discs. There was no abnormality of the peripheral joints and pigmentary deposits in the ears, sclerae, or skin were not observed."} {"id": "PMID:1271397", "title": "Application of SCAP to drug design. 1. Prediction of octanol-water partition coefficients using solvent-dependent conformational analyses.", "content": "The solvent-dependent conformational analysis procedure (SCAP) has been used to predict the octanol-water partition coefficients of 20 different compounds with an average absolute error of 9%. SCAP predicts partition coefficients almost as well as the Hansch procedure using pi constants where the absolute error for the 20 compounds is 5%. In addition to estimating partition coefficients, SCAP allows direct calculation of the corresponding solute-solvent interaction free energies. Moreover, binding free energies, based upon hydrophobic and polar interactions, may also be computed. Such free energies are not calculable using other available methods. SCAP also allows solvation free energies to be compared to, or analyzed with, the various intramolecular free energies of the solute molecule as well as all other associated conformational properties.", "contents": "Application of SCAP to drug design. 1. Prediction of octanol-water partition coefficients using solvent-dependent conformational analyses. The solvent-dependent conformational analysis procedure (SCAP) has been used to predict the octanol-water partition coefficients of 20 different compounds with an average absolute error of 9%. SCAP predicts partition coefficients almost as well as the Hansch procedure using pi constants where the absolute error for the 20 compounds is 5%. In addition to estimating partition coefficients, SCAP allows direct calculation of the corresponding solute-solvent interaction free energies. Moreover, binding free energies, based upon hydrophobic and polar interactions, may also be computed. Such free energies are not calculable using other available methods. SCAP also allows solvation free energies to be compared to, or analyzed with, the various intramolecular free energies of the solute molecule as well as all other associated conformational properties."} {"id": "PMID:1271398", "title": "Molecular connectivity. 6. Examination of the parabolic relationship between molecular connectivity and biological activity.", "content": "The topologically derived, nonempirical molecular connectivity index, chi, for several classes of compounds is shown to be parabolically related to the biological activities of these compounds. Similar nonlinear relationships were previously shown between the octanol-water partition coefficients, expressed as log P, of the compounds and their biological activities. These and previous studies indicate that many physiochemical properties presently used in structure-activity studies may be intermediaries between the nonempirical molecular structure encoded in chi and measured biological activities.", "contents": "Molecular connectivity. 6. Examination of the parabolic relationship between molecular connectivity and biological activity. The topologically derived, nonempirical molecular connectivity index, chi, for several classes of compounds is shown to be parabolically related to the biological activities of these compounds. Similar nonlinear relationships were previously shown between the octanol-water partition coefficients, expressed as log P, of the compounds and their biological activities. These and previous studies indicate that many physiochemical properties presently used in structure-activity studies may be intermediaries between the nonempirical molecular structure encoded in chi and measured biological activities."} {"id": "PMID:1271399", "title": "Quantitative structure-activity relationships. 1. The modified Free-Wilson approach.", "content": "The relationships between the linear free energy related Hansch model and the mathematical models of Free-Wilson and Bocek-Kopeck\u00fd are reviewed and discuss. Some examples are given to illustrate the theoretically derived relationships and to demonstrate scope and limitations of each mathematical model. The modified Free-Wilson approach is shown to be completely equivalent to a nonparabolic Hansch approach; it can be used to study additivity or nonadditivity of group contributions and to control and improve the fitting of Hansch equations. The Bocek-Kopeck\u00fd approach is related to the parabolic form of the Hansch approach; its practial use is limited by the great number of variables involved.", "contents": "Quantitative structure-activity relationships. 1. The modified Free-Wilson approach. The relationships between the linear free energy related Hansch model and the mathematical models of Free-Wilson and Bocek-Kopeck\u00fd are reviewed and discuss. Some examples are given to illustrate the theoretically derived relationships and to demonstrate scope and limitations of each mathematical model. The modified Free-Wilson approach is shown to be completely equivalent to a nonparabolic Hansch approach; it can be used to study additivity or nonadditivity of group contributions and to control and improve the fitting of Hansch equations. The Bocek-Kopeck\u00fd approach is related to the parabolic form of the Hansch approach; its practial use is limited by the great number of variables involved."} {"id": "PMID:1271400", "title": "Quantitative structure-activity studies on monoamine oxidase inhibitors.", "content": "Quantitative structure-activity studies were carried out on a series of N-isopropylaryl hydrazides which inhibits monoamine oxidase (MAO). The inhibitory potencies of these compounds of MAO were found to correlate with the electron-withdrawing capacity of the aryl ring substituents as estimated by both empirical Hammet sigma constants and electronic indices from molecular orbital calculations. Based on these correlations and previously published data on other classes of MAO inhibitors, a general model for the inhibitor pharmacophore is proposed: potent MAO of an aromatic ring; electron-withdrawing groups on the aromatic ring or replacing the phenyl ring with certain types of heterocyclic rings will tend to increase the potency.", "contents": "Quantitative structure-activity studies on monoamine oxidase inhibitors. Quantitative structure-activity studies were carried out on a series of N-isopropylaryl hydrazides which inhibits monoamine oxidase (MAO). The inhibitory potencies of these compounds of MAO were found to correlate with the electron-withdrawing capacity of the aryl ring substituents as estimated by both empirical Hammet sigma constants and electronic indices from molecular orbital calculations. Based on these correlations and previously published data on other classes of MAO inhibitors, a general model for the inhibitor pharmacophore is proposed: potent MAO of an aromatic ring; electron-withdrawing groups on the aromatic ring or replacing the phenyl ring with certain types of heterocyclic rings will tend to increase the potency."} {"id": "PMID:1271401", "title": "Inhibition of dihydrofolate reductase. Structure-activity correlations of quinazolines.", "content": "A quantitative structure-activity relationship (QSAR) has been formulated for quinazolines causing 50% inhibition of liver dihydrofolate reductase. The QSAR for the quinazolines is compared with QSAR for triazine and pyrimidine inhibitors. The three QSAR suggest new possibilities for the design of inhibitors of mammalian dihydrofolate reductase.", "contents": "Inhibition of dihydrofolate reductase. Structure-activity correlations of quinazolines. A quantitative structure-activity relationship (QSAR) has been formulated for quinazolines causing 50% inhibition of liver dihydrofolate reductase. The QSAR for the quinazolines is compared with QSAR for triazine and pyrimidine inhibitors. The three QSAR suggest new possibilities for the design of inhibitors of mammalian dihydrofolate reductase."} {"id": "PMID:1271402", "title": "Dependence of hydrophobicity of apolar molecules on their molecular volume.", "content": "Cavity size is the primary determinant of the partition coefficient (P) of apolar solutes between octanol and water. Although the energy of cavity formation would be expected to be related to cavity area, older methods of area calculation give a poorer correlation with log P than does volume. Apolar solutes clearly fall into two classes based on their log P/volume relationship, the distinction possibly being whether the solute exposes mostly hydrogen atoms or unbonded electrons.", "contents": "Dependence of hydrophobicity of apolar molecules on their molecular volume. Cavity size is the primary determinant of the partition coefficient (P) of apolar solutes between octanol and water. Although the energy of cavity formation would be expected to be related to cavity area, older methods of area calculation give a poorer correlation with log P than does volume. Apolar solutes clearly fall into two classes based on their log P/volume relationship, the distinction possibly being whether the solute exposes mostly hydrogen atoms or unbonded electrons."} {"id": "PMID:1271403", "title": "Direct measurement of octanol-water partition coefficients by high-pressure liquid chromatography.", "content": "A technique is presented for the direct measurement of octanol-water partition coefficients by HPLC. The method involves running solutes in octanol-saturated water as the mobile phase against water-saturated octanol entrained on an inert support. Log P correlates linearly with log tc for a number of standards. The measurable range in log P (so far) is -0.3 to +3.7. A critical review of chromatographic methods in Hansch analysis is given.", "contents": "Direct measurement of octanol-water partition coefficients by high-pressure liquid chromatography. A technique is presented for the direct measurement of octanol-water partition coefficients by HPLC. The method involves running solutes in octanol-saturated water as the mobile phase against water-saturated octanol entrained on an inert support. Log P correlates linearly with log tc for a number of standards. The measurable range in log P (so far) is -0.3 to +3.7. A critical review of chromatographic methods in Hansch analysis is given."} {"id": "PMID:1271404", "title": "Novel bis(benzamidino) compounds with an aromatic central link. Inhibitors of thrombin, pancreatic kallikrein, trypsin, and complement.", "content": "A series of novel aromatic diamidines was synthesized and evaluated for antiproteolytic activity. The compounds were distignuished by inclusion of an aromatic ring structure--either benzene or bisbenzene or naphthalene--in the link between two amidinobenzene moieties. A highly potent inhibitor of bovine thrombin was discovered in alph, alph'-bis(4-amidino-2-iodophenoxy)-p-xylene with a Ki value of 1.1 X 10(-7) M (pH 8.1, 37 degrees), while alpha, alpha'-bis(4-amidino-2-iodophenoxy)-m-xylene was found to be an outstanding inhibitor of porcine pancreatic kallikrein (Ki = 3.1 X 10(-8) M). Several of the compounds investigated also demonstrated a considerable blocking effect on typsin and on the complement-dependent immune lysis of red cells.", "contents": "Novel bis(benzamidino) compounds with an aromatic central link. Inhibitors of thrombin, pancreatic kallikrein, trypsin, and complement. A series of novel aromatic diamidines was synthesized and evaluated for antiproteolytic activity. The compounds were distignuished by inclusion of an aromatic ring structure--either benzene or bisbenzene or naphthalene--in the link between two amidinobenzene moieties. A highly potent inhibitor of bovine thrombin was discovered in alph, alph'-bis(4-amidino-2-iodophenoxy)-p-xylene with a Ki value of 1.1 X 10(-7) M (pH 8.1, 37 degrees), while alpha, alpha'-bis(4-amidino-2-iodophenoxy)-m-xylene was found to be an outstanding inhibitor of porcine pancreatic kallikrein (Ki = 3.1 X 10(-8) M). Several of the compounds investigated also demonstrated a considerable blocking effect on typsin and on the complement-dependent immune lysis of red cells."} {"id": "PMID:1271405", "title": "Synthesis and anticancer activity of 5-diethylaminomethyl derivatives and nitrogen mustards of uracil and 2-thiouracils.", "content": "Several 5-diethylaminomethyl derivatives and nitrogen mustards of uracil and 2-thiouracil have been synthesized and tested for their potential anticancer activity in vitro on KB cells and in vivo on Ehrlich carcinoma. Among the alkylating derivatives tested several showed cytotoxic activity in vitro and compound V [5-[bis(2-chloroethyl) amino] methyl-6-propyluracil hydrochloride] showed both in vitro and in vivo anticancer activity.", "contents": "Synthesis and anticancer activity of 5-diethylaminomethyl derivatives and nitrogen mustards of uracil and 2-thiouracils. Several 5-diethylaminomethyl derivatives and nitrogen mustards of uracil and 2-thiouracil have been synthesized and tested for their potential anticancer activity in vitro on KB cells and in vivo on Ehrlich carcinoma. Among the alkylating derivatives tested several showed cytotoxic activity in vitro and compound V [5-[bis(2-chloroethyl) amino] methyl-6-propyluracil hydrochloride] showed both in vitro and in vivo anticancer activity."} {"id": "PMID:1271406", "title": "Metabolic formation and synthesis of 1-(3-chlorophenyl)-2(4-hydroxyphenyl)-1-methyl-2(2 pyridine)ethanol. A potential hypocholesteremic agent.", "content": "1-(3-Chlorophenyl)-2-(4-hydroxphenyl)-1-methyl-2(2-pyridine)ethanol (8a) has been synthesized and found to be the major urinary metabolite following intraperitoneal administration of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1) to rats. This metabolite has a hypocholesteremic effect in rats similar to that of the parent drug.", "contents": "Metabolic formation and synthesis of 1-(3-chlorophenyl)-2(4-hydroxyphenyl)-1-methyl-2(2 pyridine)ethanol. A potential hypocholesteremic agent. 1-(3-Chlorophenyl)-2-(4-hydroxphenyl)-1-methyl-2(2-pyridine)ethanol (8a) has been synthesized and found to be the major urinary metabolite following intraperitoneal administration of 1-(3-chlorophenyl)-1-methyl-2-phenyl-2-(2-pyridine)ethanol (1) to rats. This metabolite has a hypocholesteremic effect in rats similar to that of the parent drug."} {"id": "PMID:1271407", "title": "Cellular pharmocodynamics of several anthrocycline antibiotics.", "content": "Alterations in the C-9 side chain of the anthracycline antibiotics, adriamycin and daunorubicin, have a profound effect on antibiotic uptake and accumulation by cultured L1210 cells. The degree of inhibition of DNA and RNA biosynthesis in the L1210 cells is directly related to the cellular uptake and accumulation of the drug analogues. Polar drug metabolites, daunorubicinol and adriamycinol, retain inhibitory activity against nucleic acid metabolism but have a decreased membrane binding and permeability. Cellular uptake and accumulation of the C-9 analogues are inversely related to drug polarity. We propose that the polarity of the anthracycline analogues contributes heavily to the differences in therapeutic index and in vivo activity through fundamental effects on membrane permeability, metabolism, and macromolecular binding.", "contents": "Cellular pharmocodynamics of several anthrocycline antibiotics. Alterations in the C-9 side chain of the anthracycline antibiotics, adriamycin and daunorubicin, have a profound effect on antibiotic uptake and accumulation by cultured L1210 cells. The degree of inhibition of DNA and RNA biosynthesis in the L1210 cells is directly related to the cellular uptake and accumulation of the drug analogues. Polar drug metabolites, daunorubicinol and adriamycinol, retain inhibitory activity against nucleic acid metabolism but have a decreased membrane binding and permeability. Cellular uptake and accumulation of the C-9 analogues are inversely related to drug polarity. We propose that the polarity of the anthracycline analogues contributes heavily to the differences in therapeutic index and in vivo activity through fundamental effects on membrane permeability, metabolism, and macromolecular binding."} {"id": "PMID:1271409", "title": "Analogues of S-adenosylhomocysteine as potential inhibitors of biological transmethylation. Synthesis of analogues with modifications at the 5'-thioether linkage.", "content": "The synthesis of S-adenosylhomocysteine analogues, in which the 5'-thioether linkage is replaced by an oxygen or nitrogen isostere, has been investigated. These compounds were disigned to be resistant to enzyme-catalyzed hydrolytic cleavage of the 5'-substituent. The amine analogue Id and two amide analogues 20 were prepared via alkylation or acylation of appropriately blocked adenosine derivatives. These new analogues were evaluated as inhibitors of catechol O-methyltransferase and tRNA methylases and found to have poor inhibitory activity.", "contents": "Analogues of S-adenosylhomocysteine as potential inhibitors of biological transmethylation. Synthesis of analogues with modifications at the 5'-thioether linkage. The synthesis of S-adenosylhomocysteine analogues, in which the 5'-thioether linkage is replaced by an oxygen or nitrogen isostere, has been investigated. These compounds were disigned to be resistant to enzyme-catalyzed hydrolytic cleavage of the 5'-substituent. The amine analogue Id and two amide analogues 20 were prepared via alkylation or acylation of appropriately blocked adenosine derivatives. These new analogues were evaluated as inhibitors of catechol O-methyltransferase and tRNA methylases and found to have poor inhibitory activity."} {"id": "PMID:1271410", "title": "Conformations and \"nictinic\" activites of cyclic analogues of choline aryl ether.", "content": "The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the minimum torsional angles about the aryl-oxygen gond geing 20, 20, 80, and 27 degrees, respectively. Since the piperidinium compound stimulates ganglia, it is concluded the either planarity of the aryl--O--C system is not essential for this type of activity or receptor interaction can involve appreciable bond distortion. The absence of ganglion-stimulant activity in the remaining compounds indicates the need for a transoid arrangement of the O--C--C--N+ system.", "contents": "Conformations and \"nictinic\" activites of cyclic analogues of choline aryl ether. The synthesis of cis and trans isomers of N,N-N-trimethyl-2-phenoxycyclohexylammonium bromide, cis-N,N,-N-trimethyl-2(2',6'-xylyloxy)cyclohexylammonium bromide, and N,N-dimethyl-3-phenoxypiperidinium bromide is described. Their structures and conformations were determined by NMR and uv absorption spectroscopy, the minimum torsional angles about the aryl-oxygen gond geing 20, 20, 80, and 27 degrees, respectively. Since the piperidinium compound stimulates ganglia, it is concluded the either planarity of the aryl--O--C system is not essential for this type of activity or receptor interaction can involve appreciable bond distortion. The absence of ganglion-stimulant activity in the remaining compounds indicates the need for a transoid arrangement of the O--C--C--N+ system."} {"id": "PMID:1271411", "title": "Sulfamylurea hypoglycemic agents. 6. High-potency derivatives.", "content": "Synthetic methods for a series of novel sulfamylurea derivatives have been developed. The hypoglycemic activity of simple 1-piperidinosulfonylureas is greatly enhanced by attaching an acylaminoethyl function in the 4 position of the piperidine ring. Optimum activity is achieved when the acyl radical is 5-chloro-2-methoxybenzoyl, 2-methoxynicotinyl, 5-chloro-2-methoxynicotinyl, 1,2-dihydro-1-methyl-2-ketonicotinyl, 2,3-ethylenedioxybenzoyl, quinoline-8-carbonyl, or 6-chloroquinoline-8-carbonyl. Optimal substituents on the terminal urea nitrogen are cyclohexyl, bicycloheptenylmethyl, and in certain cases propyl, 7-oxabicycloheptanylmethyl, and adamantyl. One of these compounds (81, gliamilide) was found to be well tolerated in man and it displayed a very short plasma half-life.", "contents": "Sulfamylurea hypoglycemic agents. 6. High-potency derivatives. Synthetic methods for a series of novel sulfamylurea derivatives have been developed. The hypoglycemic activity of simple 1-piperidinosulfonylureas is greatly enhanced by attaching an acylaminoethyl function in the 4 position of the piperidine ring. Optimum activity is achieved when the acyl radical is 5-chloro-2-methoxybenzoyl, 2-methoxynicotinyl, 5-chloro-2-methoxynicotinyl, 1,2-dihydro-1-methyl-2-ketonicotinyl, 2,3-ethylenedioxybenzoyl, quinoline-8-carbonyl, or 6-chloroquinoline-8-carbonyl. Optimal substituents on the terminal urea nitrogen are cyclohexyl, bicycloheptenylmethyl, and in certain cases propyl, 7-oxabicycloheptanylmethyl, and adamantyl. One of these compounds (81, gliamilide) was found to be well tolerated in man and it displayed a very short plasma half-life."} {"id": "PMID:1271414", "title": "Drugs derived from cannabinoids. 6. Synthesis of cyclic analogues of dimethylheptylpyran.", "content": "Two cyclic analogues 8 and 9 of dimethylheptylpyran (DMHP, 1) were synthesized by the Pechmann condensation of the resorcinol 4 with ethyl 4-methyl-2-cyclohexanone-1-carboxylate followed by Grignard addition with MeMgI. In selected pharmacological tests both analogues 8 and 9 were considered inactive compared to DMHP as CNS and cardiovascular agents.", "contents": "Drugs derived from cannabinoids. 6. Synthesis of cyclic analogues of dimethylheptylpyran. Two cyclic analogues 8 and 9 of dimethylheptylpyran (DMHP, 1) were synthesized by the Pechmann condensation of the resorcinol 4 with ethyl 4-methyl-2-cyclohexanone-1-carboxylate followed by Grignard addition with MeMgI. In selected pharmacological tests both analogues 8 and 9 were considered inactive compared to DMHP as CNS and cardiovascular agents."} {"id": "PMID:1271415", "title": "Prepartion of 16alpha-alkoxy and 16alpha-acyloxy derivatives of 21-chloro-17-acyloxy corticosteroids and determination of their vasoconstrictor activities in humans.", "content": "A number of number of 16alpha-alkoxy and 16alpha-acyloxy derivatives of 21-chloro-17-acyloxy corticosteroids have been prepared. The synthetic routes used were (a) reaction of the 16alpha,17-disubstituted 21-mesylate with lithium chloride and (b) reaction of the 16alpha-substituted 17,21-cyclic ortho ester with triphenylmethyl chloride. The vasoconstrictor activities in humans exhibited by these compounds were significantly lower than that of a 16beta-methyl analogue.", "contents": "Prepartion of 16alpha-alkoxy and 16alpha-acyloxy derivatives of 21-chloro-17-acyloxy corticosteroids and determination of their vasoconstrictor activities in humans. A number of number of 16alpha-alkoxy and 16alpha-acyloxy derivatives of 21-chloro-17-acyloxy corticosteroids have been prepared. The synthetic routes used were (a) reaction of the 16alpha,17-disubstituted 21-mesylate with lithium chloride and (b) reaction of the 16alpha-substituted 17,21-cyclic ortho ester with triphenylmethyl chloride. The vasoconstrictor activities in humans exhibited by these compounds were significantly lower than that of a 16beta-methyl analogue."} {"id": "PMID:1271416", "title": "Conformationally rigid amphetamine analogs as inhibitors of monoamine uptake by brain synaptosomes.", "content": "Four 3-phenyl-2-amino-trans-decalin isomers were synthesized in order to obtain derivatives of phenylethylamine with a rigid conformation between the phenyl ring and the amino function. The stereoisomers were tested as inhibitors of catecholamine uptake by rat brain synaptosomes, and their potency was compared with that of amphetamine. The most potent inhibitor of catecholamine uptake was the diaxial 2(a)-amino-3(a)-phenyl-trans-decalin, which was one-fourth to one-third as potent as (+/)-amphetamine. As a dopamine uptake inhibitor in the stiatum, this compound was competitive. The results differ from those obtained earlier with similar analogs with a norepinephrine moiety incorporated into the decalin structure, since a gauche derivative [2(a)-amino-3(e)-3,4-dihydroxyphenyl-3-trans-decalol] was then the most potent and over 20 times as potent as the diaxial anti derivative. It remains to be seen whether this indicates that the mode of binding of phenylethylamines is different from that of catecholamines.", "contents": "Conformationally rigid amphetamine analogs as inhibitors of monoamine uptake by brain synaptosomes. Four 3-phenyl-2-amino-trans-decalin isomers were synthesized in order to obtain derivatives of phenylethylamine with a rigid conformation between the phenyl ring and the amino function. The stereoisomers were tested as inhibitors of catecholamine uptake by rat brain synaptosomes, and their potency was compared with that of amphetamine. The most potent inhibitor of catecholamine uptake was the diaxial 2(a)-amino-3(a)-phenyl-trans-decalin, which was one-fourth to one-third as potent as (+/)-amphetamine. As a dopamine uptake inhibitor in the stiatum, this compound was competitive. The results differ from those obtained earlier with similar analogs with a norepinephrine moiety incorporated into the decalin structure, since a gauche derivative [2(a)-amino-3(e)-3,4-dihydroxyphenyl-3-trans-decalol] was then the most potent and over 20 times as potent as the diaxial anti derivative. It remains to be seen whether this indicates that the mode of binding of phenylethylamines is different from that of catecholamines."} {"id": "PMID:1271417", "title": "Partition coefficients and surface areas of some alkylbenzenes.", "content": "The experimentally measured log P values (logarithms of partition coefficients) of a number of alkylbenzenes are shown to be quantitatively related to the hydrocarbon surface area HSA of the molecule by pi = 0.0275 X HSA - 0.863 (correlation coefficient =0.996, standard deviation = 0.071). The use of surface area as a correlating parameter eliminates the need for correction factors to account for branching, cyclization, ring fusion, and \"backfolding\". Futhermore, surface area calculations provide a conceptual basis for understanding how conformation can effect partitioning.", "contents": "Partition coefficients and surface areas of some alkylbenzenes. The experimentally measured log P values (logarithms of partition coefficients) of a number of alkylbenzenes are shown to be quantitatively related to the hydrocarbon surface area HSA of the molecule by pi = 0.0275 X HSA - 0.863 (correlation coefficient =0.996, standard deviation = 0.071). The use of surface area as a correlating parameter eliminates the need for correction factors to account for branching, cyclization, ring fusion, and \"backfolding\". Futhermore, surface area calculations provide a conceptual basis for understanding how conformation can effect partitioning."} {"id": "PMID:1271418", "title": "Metabolic and photochemical hydroxylation of 5-nitro-2-furancarboxaldehyde derivatives.", "content": "The potassium salt of 1-[[(5-aco-nitro-4,5-dihydro-4-oxo-2-furanyl)methylene]amino]-2,4-imidazolidinedione (4) was isolated from the urine of rats fed nitrofurantoin. An aldehyde absorbing at 400 nm was synthesized photochemically, in less than 1% yield, from 5-nitro-2-furancarboxaldehyde diacetate (1), and the hydroxylamine (2), 3-amino-2-oxazolidinone (3a-c), and 1-amino-2,4-imidazolidinedione (4) derivatives were prepared. On the basis of ir and NMR data 2, 3b,c, and 4 are considered derivatives of 4-hydroxy-5-nitro-2-furancarboxaldehyde which are mainly in the aci-nitro form. Methyl and ethyl nitronic esters of 3b were synthesized. The photochemical hydroxylation of 1 also yields 3,4-dihydroxy-5-nitro-2-furancarboxaldehyde, isolated as 3-[[(3,4-dimethoxy-5-nitro-2-furanyl)-methylene[amino[-2-oxazolidinone (7).", "contents": "Metabolic and photochemical hydroxylation of 5-nitro-2-furancarboxaldehyde derivatives. The potassium salt of 1-[[(5-aco-nitro-4,5-dihydro-4-oxo-2-furanyl)methylene]amino]-2,4-imidazolidinedione (4) was isolated from the urine of rats fed nitrofurantoin. An aldehyde absorbing at 400 nm was synthesized photochemically, in less than 1% yield, from 5-nitro-2-furancarboxaldehyde diacetate (1), and the hydroxylamine (2), 3-amino-2-oxazolidinone (3a-c), and 1-amino-2,4-imidazolidinedione (4) derivatives were prepared. On the basis of ir and NMR data 2, 3b,c, and 4 are considered derivatives of 4-hydroxy-5-nitro-2-furancarboxaldehyde which are mainly in the aci-nitro form. Methyl and ethyl nitronic esters of 3b were synthesized. The photochemical hydroxylation of 1 also yields 3,4-dihydroxy-5-nitro-2-furancarboxaldehyde, isolated as 3-[[(3,4-dimethoxy-5-nitro-2-furanyl)-methylene[amino[-2-oxazolidinone (7)."} {"id": "PMID:1271419", "title": "Antidepressant and anticonvulsant activity of 1-(5-phenyl-4-oxazolin-2-yl)-4-substituted piperazines.", "content": "1-(5-Phenyl-4-oxo-2-oxazolin-2-yl)-4-substituted cinnamoylpiperazines and 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)-4-carbamoylpiperazine and derivatives were synthesized and evaluated for antidepressant activity in the mouse Dopa potentiation test. 1-(5-Phenyl-4-oxo-2-oxazolin-2-yl)-4-carbamoylpiperazine and derivatives were further evaluated for anticonvulsant activity in the audiogenic seizure test in mice.", "contents": "Antidepressant and anticonvulsant activity of 1-(5-phenyl-4-oxazolin-2-yl)-4-substituted piperazines. 1-(5-Phenyl-4-oxo-2-oxazolin-2-yl)-4-substituted cinnamoylpiperazines and 1-(5-phenyl-4-oxo-2-oxazolin-2-yl)-4-carbamoylpiperazine and derivatives were synthesized and evaluated for antidepressant activity in the mouse Dopa potentiation test. 1-(5-Phenyl-4-oxo-2-oxazolin-2-yl)-4-carbamoylpiperazine and derivatives were further evaluated for anticonvulsant activity in the audiogenic seizure test in mice."} {"id": "PMID:1271421", "title": "Aspects of pre-eclamptic toxaemia of pregnancy, consanguinity, twinning in Ankara.", "content": "It appears that women classed as having pre-eclamptic toxaemia are less frequently consanguineous with their husbands than all other mothers and in particular those mothers classed as having pregnancies complicated by chronic hypertensive disease. Search revealed no evidence for possible biases which could have stimulated such findings. Further evidence is advanced suggesting that, though pre-eclamptic toxaemia is more common in all types of twin pregnancies than in single births, it is more common where the twins are dizygous than where they are monozygous. It is pointed out that both these findings would be expected if there was a contribution to the aetiology of pre-eclamptic toxaemia by maternal/fetal immunological incompatibility. However, if such a mechanism exists it is not always determined at the same gene locus.", "contents": "Aspects of pre-eclamptic toxaemia of pregnancy, consanguinity, twinning in Ankara. It appears that women classed as having pre-eclamptic toxaemia are less frequently consanguineous with their husbands than all other mothers and in particular those mothers classed as having pregnancies complicated by chronic hypertensive disease. Search revealed no evidence for possible biases which could have stimulated such findings. Further evidence is advanced suggesting that, though pre-eclamptic toxaemia is more common in all types of twin pregnancies than in single births, it is more common where the twins are dizygous than where they are monozygous. It is pointed out that both these findings would be expected if there was a contribution to the aetiology of pre-eclamptic toxaemia by maternal/fetal immunological incompatibility. However, if such a mechanism exists it is not always determined at the same gene locus."} {"id": "PMID:1271422", "title": "Linkage relationships between beta- and delta-structural loci and African forms of beta thalassaemia.", "content": "Five families are described in which there have been matings between individuals doubly heterozygous for beta thalassaemia and the delta-chain variant haemoglobin A2' to normal persons. In all there were 24 informative offspring. There were no crossovers between the beta-thalassaemia and delta-chain loci; in three of the families the genes were linked in cis and in two families the genes were found in trans. Together with previously reported families there have now been 58 opportunities for crossing over between the beta-thalassaemia and delta-chain loci and there have been two possible and one highly probable crossovers. Of the total of 9 families reported to date 4 have had the genes for beta thalassaemia and Hb A2' in cis and 5 in trans. These findings are contrasted with the findings in families where a beta-chain structural variant and Hb A2' have been observed together and these genes have always been found in trans and never in cis. The reasons for linkage disequilibrium of this type are discussed. It is concluded tentatively that the distance between the delta-structural and beta-thalassaemia loci is greater than that between the delta-structural and beta-structural loci. To date this conclusion can only be applied to the beta+ -thalassaemia and beta-thalassaemia genes as found in the African population, since this is the only population with a high incidence of delta-chain mutants which allow linkage analysis of this type to be carried out.", "contents": "Linkage relationships between beta- and delta-structural loci and African forms of beta thalassaemia. Five families are described in which there have been matings between individuals doubly heterozygous for beta thalassaemia and the delta-chain variant haemoglobin A2' to normal persons. In all there were 24 informative offspring. There were no crossovers between the beta-thalassaemia and delta-chain loci; in three of the families the genes were linked in cis and in two families the genes were found in trans. Together with previously reported families there have now been 58 opportunities for crossing over between the beta-thalassaemia and delta-chain loci and there have been two possible and one highly probable crossovers. Of the total of 9 families reported to date 4 have had the genes for beta thalassaemia and Hb A2' in cis and 5 in trans. These findings are contrasted with the findings in families where a beta-chain structural variant and Hb A2' have been observed together and these genes have always been found in trans and never in cis. The reasons for linkage disequilibrium of this type are discussed. It is concluded tentatively that the distance between the delta-structural and beta-thalassaemia loci is greater than that between the delta-structural and beta-structural loci. To date this conclusion can only be applied to the beta+ -thalassaemia and beta-thalassaemia genes as found in the African population, since this is the only population with a high incidence of delta-chain mutants which allow linkage analysis of this type to be carried out."} {"id": "PMID:1271423", "title": "Consanguinity and familial mental retardation.", "content": "Studies made in a group of patients with mental retardation showed that there was a high degree of parental consanguinity of the order of 30.3%. Index cases with parental consanguinity showed a relatively higher prevalence where more than one sib was affected. Cases with metabolic defects were also more common among cases with parental consanguinity. There is a need for studies in the general population in order to understand the biological significance of consanguinity.", "contents": "Consanguinity and familial mental retardation. Studies made in a group of patients with mental retardation showed that there was a high degree of parental consanguinity of the order of 30.3%. Index cases with parental consanguinity showed a relatively higher prevalence where more than one sib was affected. Cases with metabolic defects were also more common among cases with parental consanguinity. There is a need for studies in the general population in order to understand the biological significance of consanguinity."} {"id": "PMID:1271424", "title": "Behaviour of cell cultures from human amniotic fluid.", "content": "The growth pattern of cell cultures originating from 11 amniotic fluid specimens have been observed. From each specimen 2 to 12 primary cultures were set up. In most cases growth started simultaneously in the primary cultures originating from one sample. The primary cultures lasted from 7 to 30 days. A variation was found both between cultures from different pregnancies as well as among cultures obtained from single amniotic fluids. The growth period from setting up the cultures until harvest of the cell lines for biochemical analysis ranged from 20 to 54 days. No connexion was noticed between the time spent in primary culture and the behaviour of the cell line before harvest. The effects of two types of serum (fetal calf serum and pooled human serum) on the behaviour of the cultures were compared. The cells grown in human serum were harvested a few days before those grown in fetal calf serum. The influence of different batches of medium was also examined; no significant effect of the growth pattern was found. The appearance of epithelial-like and fibroblast-like cells in cultures from 6 specimens was observed concurrently. At the time of harvest the cell lines originating from the same amniotic specimen contained the cell types in different proportions.", "contents": "Behaviour of cell cultures from human amniotic fluid. The growth pattern of cell cultures originating from 11 amniotic fluid specimens have been observed. From each specimen 2 to 12 primary cultures were set up. In most cases growth started simultaneously in the primary cultures originating from one sample. The primary cultures lasted from 7 to 30 days. A variation was found both between cultures from different pregnancies as well as among cultures obtained from single amniotic fluids. The growth period from setting up the cultures until harvest of the cell lines for biochemical analysis ranged from 20 to 54 days. No connexion was noticed between the time spent in primary culture and the behaviour of the cell line before harvest. The effects of two types of serum (fetal calf serum and pooled human serum) on the behaviour of the cultures were compared. The cells grown in human serum were harvested a few days before those grown in fetal calf serum. The influence of different batches of medium was also examined; no significant effect of the growth pattern was found. The appearance of epithelial-like and fibroblast-like cells in cultures from 6 specimens was observed concurrently. At the time of harvest the cell lines originating from the same amniotic specimen contained the cell types in different proportions."} {"id": "PMID:1271425", "title": "New allele at cholinesterase locus 1.", "content": "A family (H-J pedigree) segregating for the A and F alleles at cholinesterase locus 1 is described. Apparent anomalous results led to the recognition of a new allele (E1j) also segregating in the family. The data are consistent with the hypothesis that the the E1j causes reduction of 'usual' (E1u) molecules by about 66%. Whether this is because of retarded synthesis or accelerated degradation of serum cholinesterase remains to be determined.", "contents": "New allele at cholinesterase locus 1. A family (H-J pedigree) segregating for the A and F alleles at cholinesterase locus 1 is described. Apparent anomalous results led to the recognition of a new allele (E1j) also segregating in the family. The data are consistent with the hypothesis that the the E1j causes reduction of 'usual' (E1u) molecules by about 66%. Whether this is because of retarded synthesis or accelerated degradation of serum cholinesterase remains to be determined."} {"id": "PMID:1271426", "title": "Prenatal diagnosis of Wolman's disease.", "content": "Amniocentesis was performed in the 15th week of a pregnancy at risk for Wolman's disease. The cultured amniotic fluid cells were found to have a severe deficiency of acid esterase activity consistent with homozygosity of the fetus. The pregnancy was terminated in the 19th week and the prenatal diagnosis confirmed by enzymic and chemical evaluation of the fetal tissues.", "contents": "Prenatal diagnosis of Wolman's disease. Amniocentesis was performed in the 15th week of a pregnancy at risk for Wolman's disease. The cultured amniotic fluid cells were found to have a severe deficiency of acid esterase activity consistent with homozygosity of the fetus. The pregnancy was terminated in the 19th week and the prenatal diagnosis confirmed by enzymic and chemical evaluation of the fetal tissues."} {"id": "PMID:1271427", "title": "The Gardner syndrome: increased tetraploidy in cultured skin fibroblast.", "content": "Tetraploidy was increased in skin fibroblast cultures grown in the laboratory at the same time under the same conditions and derived from 2 probands with the Gardner syndrome and 9 affected members of one family as compared to that occurring in cultures from 5 relatives by marriage and 10 normals. Tetraploidy was present at the first subculture (2 weeks after the initial biopsy was cultured), and for each line studied the percentage of dividing cells showing tetraploidy remained constant. The relation of the observed tetraploidy to the increased risk of such patients to develop abnormal growths and cancer has not been established. The increased tetraploidy should be of value in identifying the presence of the gene for the Gardner syndrome in high risk families.", "contents": "The Gardner syndrome: increased tetraploidy in cultured skin fibroblast. Tetraploidy was increased in skin fibroblast cultures grown in the laboratory at the same time under the same conditions and derived from 2 probands with the Gardner syndrome and 9 affected members of one family as compared to that occurring in cultures from 5 relatives by marriage and 10 normals. Tetraploidy was present at the first subculture (2 weeks after the initial biopsy was cultured), and for each line studied the percentage of dividing cells showing tetraploidy remained constant. The relation of the observed tetraploidy to the increased risk of such patients to develop abnormal growths and cancer has not been established. The increased tetraploidy should be of value in identifying the presence of the gene for the Gardner syndrome in high risk families."} {"id": "PMID:1271429", "title": "An XX female with sexual infantilism, absent gonads, and lack of M\u00fcllerian ducts.", "content": "A patient with a 46,XX chromosome constitution showed the following main characteristics: lack of secondary sexual development, female external genitalia with absence of vagina, no gonadal structures, and complete lack of internal genitalia. This is a variant of the gonadal agenesis syndrome so far only described in association with and XY chromosome component. Endrocinology demonstrated that in the absence of gonadal feedback the pituitary responsiveness to synthetic luteinizing hormone-releasing hormone was increased.", "contents": "An XX female with sexual infantilism, absent gonads, and lack of M\u00fcllerian ducts. A patient with a 46,XX chromosome constitution showed the following main characteristics: lack of secondary sexual development, female external genitalia with absence of vagina, no gonadal structures, and complete lack of internal genitalia. This is a variant of the gonadal agenesis syndrome so far only described in association with and XY chromosome component. Endrocinology demonstrated that in the absence of gonadal feedback the pituitary responsiveness to synthetic luteinizing hormone-releasing hormone was increased."} {"id": "PMID:1271430", "title": "Further observations on the Birmingham chimaera.", "content": "The appropriate ABH-gene specified glycosyltransferases in the plasma of the Birmingham chimaera were estimated. These observatiions and the demonstration of A1Leb blood group specific glycosphingolipid in the plasma indicate that the minority population of red blood cells probably represents the true blood groups of the patient.", "contents": "Further observations on the Birmingham chimaera. The appropriate ABH-gene specified glycosyltransferases in the plasma of the Birmingham chimaera were estimated. These observatiions and the demonstration of A1Leb blood group specific glycosphingolipid in the plasma indicate that the minority population of red blood cells probably represents the true blood groups of the patient."} {"id": "PMID:1271431", "title": "A case of hypogonadotrophic hypogonadism with anosmia (Kallmann's syndrome) in a male, with familial incidence of a small metacentric chromosome (47,XX, mat?+).", "content": "A case of Kallmann's syndrome in a male is reported. Besides the classical picture of hypogonadotrophic hypogonadism (demonstrated both by endocrine investigation and a testicular biopsy) with anosmia, a number of other unusual features are present including gynaecomastia, agencies of the anterior brachial muscles, some dental abnormalities, and dyschromatopsy. The karyotype, studied on peripheral lymphocytes, shows, in the propositus as well as in his mother, the presence in all mitoses of an extra small metacentric chromosome; its derivation is uncertain.", "contents": "A case of hypogonadotrophic hypogonadism with anosmia (Kallmann's syndrome) in a male, with familial incidence of a small metacentric chromosome (47,XX, mat?+). A case of Kallmann's syndrome in a male is reported. Besides the classical picture of hypogonadotrophic hypogonadism (demonstrated both by endocrine investigation and a testicular biopsy) with anosmia, a number of other unusual features are present including gynaecomastia, agencies of the anterior brachial muscles, some dental abnormalities, and dyschromatopsy. The karyotype, studied on peripheral lymphocytes, shows, in the propositus as well as in his mother, the presence in all mitoses of an extra small metacentric chromosome; its derivation is uncertain."} {"id": "PMID:1271432", "title": "Trigonocephaly and associated minor anomalies in mother and son.", "content": "A mother and her son are described with neonatal trigonocephaly, multiple suture synostosis; shallow orbits; unusual nose; deviation of the terminal phalanges of fingers 1, 2, and 5; and broad toes which radiologically may show duplication of the terminal phalanx. Untreated, the condition leads to a disfiguring oxycephaly with hypotelorism. This appears to be the first documented instance of autosomal dominant trigonocephaly. The importance of the minor anomalies in its recognition and its good prognosis are emphasized.", "contents": "Trigonocephaly and associated minor anomalies in mother and son. A mother and her son are described with neonatal trigonocephaly, multiple suture synostosis; shallow orbits; unusual nose; deviation of the terminal phalanges of fingers 1, 2, and 5; and broad toes which radiologically may show duplication of the terminal phalanx. Untreated, the condition leads to a disfiguring oxycephaly with hypotelorism. This appears to be the first documented instance of autosomal dominant trigonocephaly. The importance of the minor anomalies in its recognition and its good prognosis are emphasized."} {"id": "PMID:1271435", "title": "Loans for medical students: the issue of manageability.", "content": "Unless there is a shift in student aid policy for medical students to a greater proportion of scholarships or grants, increased student borrowing is inevitable. This paper is concerned with the structure of student loan programs and with altering the repayment features of the programs for the convenience of the student borrower. In this context the Guaranteed Student Loan Program is analyzed and its current limitations discussed. A variant of the GSL program having an income contingent repayment feature is proposed. Computer simulations of loan repayments with the proposed income contingent variant and the current program using current and projected data on physicians' incomes are developed. Based on the results of these simulations, some conclusions regarding the manageability of repayments with the proposed loan program are presented.", "contents": "Loans for medical students: the issue of manageability. Unless there is a shift in student aid policy for medical students to a greater proportion of scholarships or grants, increased student borrowing is inevitable. This paper is concerned with the structure of student loan programs and with altering the repayment features of the programs for the convenience of the student borrower. In this context the Guaranteed Student Loan Program is analyzed and its current limitations discussed. A variant of the GSL program having an income contingent repayment feature is proposed. Computer simulations of loan repayments with the proposed income contingent variant and the current program using current and projected data on physicians' incomes are developed. Based on the results of these simulations, some conclusions regarding the manageability of repayments with the proposed loan program are presented."} {"id": "PMID:1271436", "title": "Selecting a few residents from many applicants: a new way to be fair and efficient.", "content": "Selection of residents from among the large number of qualified applicants is an annual task requiring a significant commitment of resources by teaching hospitals. A method based on sound principles of decision-making and utilizing a computer analysis for initial ranking of applicants was developed to improve the selection process. The result was satisfactory selection with significant savings of time and effort for the residency program faculty.", "contents": "Selecting a few residents from many applicants: a new way to be fair and efficient. Selection of residents from among the large number of qualified applicants is an annual task requiring a significant commitment of resources by teaching hospitals. A method based on sound principles of decision-making and utilizing a computer analysis for initial ranking of applicants was developed to improve the selection process. The result was satisfactory selection with significant savings of time and effort for the residency program faculty."} {"id": "PMID:1271437", "title": "What happens to creative medical students?", "content": "A psychometric index of creative potential was devised by relating test scores to ratings of creativity in samples of architects, engineers, mathematicians, psychologists, and research scientists. A correlation of .45 was obtained between scores on this index and the criterion ratings in the total initial sample of 350 men. The tests used to compute scores on the index were also available for 284 first-year medical students being studied as physicians in a longitudinal inquiry on speciality choice and location of practice. The mean creativity score of the medical students was higher than that for any of the other samples. Within the array of means for medical specialty groups, psychiatrists ranked first and internists second. Students who failed to complete medical school also scored high, suggesting that dropping out is not just a matter of poor academic potential or unsuitability for a career in medicine.", "contents": "What happens to creative medical students? A psychometric index of creative potential was devised by relating test scores to ratings of creativity in samples of architects, engineers, mathematicians, psychologists, and research scientists. A correlation of .45 was obtained between scores on this index and the criterion ratings in the total initial sample of 350 men. The tests used to compute scores on the index were also available for 284 first-year medical students being studied as physicians in a longitudinal inquiry on speciality choice and location of practice. The mean creativity score of the medical students was higher than that for any of the other samples. Within the array of means for medical specialty groups, psychiatrists ranked first and internists second. Students who failed to complete medical school also scored high, suggesting that dropping out is not just a matter of poor academic potential or unsuitability for a career in medicine."} {"id": "PMID:1271438", "title": "Effectiveness of an international health elective as measured by NBME Part II.", "content": "A total of 434 third- and fourth- year medical students from 80 U.S. medical schools participate between 1968 and 1974 in Yugoslav or Israeli international fellowship programs sponsored by the Association of American Medical Colleges and the U.S. Public Health Service. Subsequently, the scores of these fellowship student on Part II of the examinations of the National Board of Medical Examiners (NBME) were compared with the scores of rejected applicants and with the national average to determine the cognitive impact of the fellowship experience on the participants. The results show that the international fellows scored significantly higher than the rejected applicants and the national average in only the preventive medicine/public health portion of the examination. The conclusion is drawn that the fellowship programs enhanced the participants' knowledge of preventive medicine and public health.", "contents": "Effectiveness of an international health elective as measured by NBME Part II. A total of 434 third- and fourth- year medical students from 80 U.S. medical schools participate between 1968 and 1974 in Yugoslav or Israeli international fellowship programs sponsored by the Association of American Medical Colleges and the U.S. Public Health Service. Subsequently, the scores of these fellowship student on Part II of the examinations of the National Board of Medical Examiners (NBME) were compared with the scores of rejected applicants and with the national average to determine the cognitive impact of the fellowship experience on the participants. The results show that the international fellows scored significantly higher than the rejected applicants and the national average in only the preventive medicine/public health portion of the examination. The conclusion is drawn that the fellowship programs enhanced the participants' knowledge of preventive medicine and public health."} {"id": "PMID:1271439", "title": "Evaluating student performance in a decentralized basic science program.", "content": "The results of the evaluation of the basic science curriculum in a regionalized medical education program in the states of Washington, Alaska, Montana, and Idaho (WAMI) are presented and discussed. The hypothesis that students taking the first quarter of basic science at universities remote from the Unversity of Washington School of Medicine (UWSM) will be no different in academic performance from those who remain at the UWSM is tested. The variables considered were student performance on (a) common tests in Anatomy/Histology, Biochemistry, Mechanisms of Physiology, and Epidemiology; (b) subsequent course work at the UWSM; and (c) the mini-tests and Part I of the examinations of the National Board of Medical Examiners. The developement of the common tests is described. Analysis of variance indicates that the null hypothesis cannot be rejected at the .05 level.", "contents": "Evaluating student performance in a decentralized basic science program. The results of the evaluation of the basic science curriculum in a regionalized medical education program in the states of Washington, Alaska, Montana, and Idaho (WAMI) are presented and discussed. The hypothesis that students taking the first quarter of basic science at universities remote from the Unversity of Washington School of Medicine (UWSM) will be no different in academic performance from those who remain at the UWSM is tested. The variables considered were student performance on (a) common tests in Anatomy/Histology, Biochemistry, Mechanisms of Physiology, and Epidemiology; (b) subsequent course work at the UWSM; and (c) the mini-tests and Part I of the examinations of the National Board of Medical Examiners. The developement of the common tests is described. Analysis of variance indicates that the null hypothesis cannot be rejected at the .05 level."} {"id": "PMID:1271440", "title": "A computer-assisted admission matching system for the University of Texas medical schools.", "content": "The feasibility of a computer-assisted admission matching system was investigated in 1973-74 at the Medical and Dental Application Center at the request of the four University of Texas medical schools. Preference data were gathered from applicants and from schools, and matching simulation was conducted concurrently with actual admission action for 1974 entering classes. Implementation of a matching system for admission of the 1975 entering classes was demonstrated to be feasible, and a decision to implement such a system was made. Data indicating the need for a matching system are briefly reviewed, and the matching concept is discussed. Results of the 1974 feasibility study are presented, and the first year of implementation for the 1975 entering classes is described. Admission matching improved the efficiency of the admission process by reducing the number of unproductive offers of admission and by providing more applicants earlier decisions from participating schools regarding their applications.", "contents": "A computer-assisted admission matching system for the University of Texas medical schools. The feasibility of a computer-assisted admission matching system was investigated in 1973-74 at the Medical and Dental Application Center at the request of the four University of Texas medical schools. Preference data were gathered from applicants and from schools, and matching simulation was conducted concurrently with actual admission action for 1974 entering classes. Implementation of a matching system for admission of the 1975 entering classes was demonstrated to be feasible, and a decision to implement such a system was made. Data indicating the need for a matching system are briefly reviewed, and the matching concept is discussed. Results of the 1974 feasibility study are presented, and the first year of implementation for the 1975 entering classes is described. Admission matching improved the efficiency of the admission process by reducing the number of unproductive offers of admission and by providing more applicants earlier decisions from participating schools regarding their applications."} {"id": "PMID:1271441", "title": "Cancer centers: their relationship to the academic community.", "content": "During the past decade one important change that has occurred in medical education has been the development of multidisciplinary research, education, and treatment efforts by new groups of scholars drawn from multiple disciplines. In their daily activities members of such groups have more in common with their new affinity group than with their traditional discipline. Yet important adminstrative functions such as appointment, assignment of space, and allocation of budget are conducted by separate administrative units. This has produced stress and conflict within many academic institutions. Some of the lessons learned by institutions participating in the cancer center program may be generally applicable. Comprehensive cancer centers have evolved several types of administrative sturctures, but there is a common characteristics among the most successful. Each has developed some modification of a matrix system with delegation of significant administrative authority to the center. If the matrix approach is successful in cancer, it may become a pattern for other programs in the future.", "contents": "Cancer centers: their relationship to the academic community. During the past decade one important change that has occurred in medical education has been the development of multidisciplinary research, education, and treatment efforts by new groups of scholars drawn from multiple disciplines. In their daily activities members of such groups have more in common with their new affinity group than with their traditional discipline. Yet important adminstrative functions such as appointment, assignment of space, and allocation of budget are conducted by separate administrative units. This has produced stress and conflict within many academic institutions. Some of the lessons learned by institutions participating in the cancer center program may be generally applicable. Comprehensive cancer centers have evolved several types of administrative sturctures, but there is a common characteristics among the most successful. Each has developed some modification of a matrix system with delegation of significant administrative authority to the center. If the matrix approach is successful in cancer, it may become a pattern for other programs in the future."} {"id": "PMID:1271442", "title": "The lecture: increasing student learning.", "content": "This study involved a single lecture given to second-year medical students. Its purpose was to detemine whether significant learning of the lecture content could occur during the lecture. The author's criteria for \"significant\" learning was mastery of 75 percent of what he predetermined to be the important of \"required\" content plus T-test analysis of pretest-posttest learning. The class divided into Groups A and B. At the commencement of the lecture Group A took Test 1 as its pretest and Group B took Test 2. Immediately following the lecture Group A took Test 2 as its posttest and Group B took Test 1. Comparing Test 1 with Test 2 as pretests and again as posttest, they were not significantly different at the .05 level. However, Group A's posttest scores were significantly higher than its pretest scores (p less than .005). The same was found for Group B, with both groups' averaging over 90 percent mastery of the required content and demonstrating that significant learning occurred during the lecture.", "contents": "The lecture: increasing student learning. This study involved a single lecture given to second-year medical students. Its purpose was to detemine whether significant learning of the lecture content could occur during the lecture. The author's criteria for \"significant\" learning was mastery of 75 percent of what he predetermined to be the important of \"required\" content plus T-test analysis of pretest-posttest learning. The class divided into Groups A and B. At the commencement of the lecture Group A took Test 1 as its pretest and Group B took Test 2. Immediately following the lecture Group A took Test 2 as its posttest and Group B took Test 1. Comparing Test 1 with Test 2 as pretests and again as posttest, they were not significantly different at the .05 level. However, Group A's posttest scores were significantly higher than its pretest scores (p less than .005). The same was found for Group B, with both groups' averaging over 90 percent mastery of the required content and demonstrating that significant learning occurred during the lecture."} {"id": "PMID:1271443", "title": "The use of test results from ASA workshops to evaluate workshop effectiveness.", "content": "Results of tests given to participants in six American Society of Anesthesiologists workshops were analyzed to detemine whether attendance at the workshops increased the participants' scores on sequential tests. Those who attended the workshops took the same test prior to, immediately after, and three months after the workshop. Two control groups of anesthesiologists took the tests in the same time sequence for comparison. Both workshop and control groups increased their scores with each successive test. In only one instance did those who attended the workshop improve their scores significantly more than did the control group. Because of difficulties inherent in designing valid and reliable tests, further development of the testing technique currently used at the workshops is necessary to make it a useful measure of workshop effectiveness.", "contents": "The use of test results from ASA workshops to evaluate workshop effectiveness. Results of tests given to participants in six American Society of Anesthesiologists workshops were analyzed to detemine whether attendance at the workshops increased the participants' scores on sequential tests. Those who attended the workshops took the same test prior to, immediately after, and three months after the workshop. Two control groups of anesthesiologists took the tests in the same time sequence for comparison. Both workshop and control groups increased their scores with each successive test. In only one instance did those who attended the workshop improve their scores significantly more than did the control group. Because of difficulties inherent in designing valid and reliable tests, further development of the testing technique currently used at the workshops is necessary to make it a useful measure of workshop effectiveness."} {"id": "PMID:1271448", "title": "The teaching of child psychiatry in U.S. medical schools: results of a survey.", "content": "The major results of this survey are that most schools have special programs in child psychiatry and that these are distinct from the adult psychiatry course. The course content involves clinical evaluation of children, information on child development and psychopathology, assigned reading, and liaison with pediatrics. Most schools have full-time psychiatrists on their faculty, and the child psychiatry course is taught by child psychiatrists; but less than 20 percent of the psychiatric faculty are child psychiatrists in a majority of the schools in the country. Finally, although evaluation by students and faculty is common in most of the schools, only slightly more than one-third of the institutions gave grades in child psychiatry and slightly fewer than one-third gave examinations in this subject.", "contents": "The teaching of child psychiatry in U.S. medical schools: results of a survey. The major results of this survey are that most schools have special programs in child psychiatry and that these are distinct from the adult psychiatry course. The course content involves clinical evaluation of children, information on child development and psychopathology, assigned reading, and liaison with pediatrics. Most schools have full-time psychiatrists on their faculty, and the child psychiatry course is taught by child psychiatrists; but less than 20 percent of the psychiatric faculty are child psychiatrists in a majority of the schools in the country. Finally, although evaluation by students and faculty is common in most of the schools, only slightly more than one-third of the institutions gave grades in child psychiatry and slightly fewer than one-third gave examinations in this subject."} {"id": "PMID:1271453", "title": "Feasibility studies of evoked response audiometry in the mentally subnormal.", "content": "Evoked response audiometry was attempted on a group of seventy-seven unsedated severly subnormal patients up to the age of twenty-two years. Data of some clinical value were obtained in fifty-seven cases. It is suggested that sedation need only be used if the initial attempt at E.R.A. is unsuccessful. Over twenty per cent of the subjects appeared to have significant hearing loss.", "contents": "Feasibility studies of evoked response audiometry in the mentally subnormal. Evoked response audiometry was attempted on a group of seventy-seven unsedated severly subnormal patients up to the age of twenty-two years. Data of some clinical value were obtained in fifty-seven cases. It is suggested that sedation need only be used if the initial attempt at E.R.A. is unsuccessful. Over twenty per cent of the subjects appeared to have significant hearing loss."} {"id": "PMID:1271454", "title": "Resistance to extinction as a function of IQ and reinforcement ratio among retarded children.", "content": "Children at three levels of mental retardation (IQ ranges of 50-60, 30-40 and 20-below) were trained to bar-press on one of two variable ratio (V.R.) schedules. Responses were reinforced twenty-five times on either a V.R.2 or V.R.4 schedule. Analysis of the number of responses during extinction indicated an inverse relationship between IQ and resistance to extinction. The period reinforcement extinction effect was found, but there was no interaction with IQ level. The results support the position that inhibitory control is an important parameter along which intelligence may be ordered.", "contents": "Resistance to extinction as a function of IQ and reinforcement ratio among retarded children. Children at three levels of mental retardation (IQ ranges of 50-60, 30-40 and 20-below) were trained to bar-press on one of two variable ratio (V.R.) schedules. Responses were reinforced twenty-five times on either a V.R.2 or V.R.4 schedule. Analysis of the number of responses during extinction indicated an inverse relationship between IQ and resistance to extinction. The period reinforcement extinction effect was found, but there was no interaction with IQ level. The results support the position that inhibitory control is an important parameter along which intelligence may be ordered."} {"id": "PMID:1271455", "title": "The syndrome of Coffin, Siris and Wegienka: report of a case.", "content": "A severely subnormal male with the syndrome of Coffin, Siris and Wegienka is described and compared with previously reported cases. The possible aetiology is discussed.", "contents": "The syndrome of Coffin, Siris and Wegienka: report of a case. A severely subnormal male with the syndrome of Coffin, Siris and Wegienka is described and compared with previously reported cases. The possible aetiology is discussed."} {"id": "PMID:1271456", "title": "Spontaneous fluctuation in rate of body rocking: a methodological note.", "content": "Descriptive data are presented on the natural occurrence of stereotyped body rocking in three institutionalised, mentally retarded children. Both ward and test situation observations suggest that there is spontaneous fluctuation in rate of body rocking. These findings raise a serious methodological problem pertinent to the evaluation of experimental data on stereotyped behaviour: rate change attributed to experimental manipulation may in fact only be an instance of spontaneous fluctuation.", "contents": "Spontaneous fluctuation in rate of body rocking: a methodological note. Descriptive data are presented on the natural occurrence of stereotyped body rocking in three institutionalised, mentally retarded children. Both ward and test situation observations suggest that there is spontaneous fluctuation in rate of body rocking. These findings raise a serious methodological problem pertinent to the evaluation of experimental data on stereotyped behaviour: rate change attributed to experimental manipulation may in fact only be an instance of spontaneous fluctuation."} {"id": "PMID:1271457", "title": "Short-cycle manic depressive psychosis in mental defectives: a clinical and physiological study.", "content": "The clinical features of four cases of short-cycle manic depressive psychosis occurring in mentally defective patients are described. Behavioural fluctuations are correlated with alterations in sleep pattern, pulse rate and temperature. The diagnostic problems and significance of the observations are discussed.", "contents": "Short-cycle manic depressive psychosis in mental defectives: a clinical and physiological study. The clinical features of four cases of short-cycle manic depressive psychosis occurring in mentally defective patients are described. Behavioural fluctuations are correlated with alterations in sleep pattern, pulse rate and temperature. The diagnostic problems and significance of the observations are discussed."} {"id": "PMID:1271458", "title": "Obesity in an institutionalised adult mentally retarded population.", "content": "The frequency of obesity, as defined by standards based on triceps skinfold, and selected body measurements are reported in an institutionalised adult mentally retarded population. Among 161 adults, aged eighteen to seventy-three years, twenty-two out of 108 males (20.4 per cent) and nine out of fifty-three females (17.0 per cent) were obese. These findings suggest that obesity is a significant health-related problem in institutionalised retarded adults. Although differences were not statistically significant, the frequency of obesity was higher in moderately retarded than in mildly or severely retarded residents. Further surveys are needed of larger samples, along with studies of possible contributory factors (e.g., dietary habits and level of physical activity).", "contents": "Obesity in an institutionalised adult mentally retarded population. The frequency of obesity, as defined by standards based on triceps skinfold, and selected body measurements are reported in an institutionalised adult mentally retarded population. Among 161 adults, aged eighteen to seventy-three years, twenty-two out of 108 males (20.4 per cent) and nine out of fifty-three females (17.0 per cent) were obese. These findings suggest that obesity is a significant health-related problem in institutionalised retarded adults. Although differences were not statistically significant, the frequency of obesity was higher in moderately retarded than in mildly or severely retarded residents. Further surveys are needed of larger samples, along with studies of possible contributory factors (e.g., dietary habits and level of physical activity)."} {"id": "PMID:1271476", "title": "Sex is a family affair: sources of discord and harmony.", "content": "Sexuality is a central source of communication and growth in the development of relationships between an individual and his parents, spouse, and children. It is both a vehicle for and manifestation of crucial interpersonal links. In the physical sense, this is seen when the adolescent or adult's physical sexual expression is evidence of closeness to another and it also a way of achieving such closeness. In the psychological sense, sexual behavior in current relationships may be hindered by carrying the image of internalized aspects of past relationships; it may also afford a new setting for further work on them. This paper explores family aspects of sexual issues in several areas, demonstrating that when sexual dysfunction represents the distillation of a couple's relationship to their own parents, successful resolution of their own sexual relationship may be a crucial first step in rebuilding family harmony and providing a culture of intimacy for their children.", "contents": "Sex is a family affair: sources of discord and harmony. Sexuality is a central source of communication and growth in the development of relationships between an individual and his parents, spouse, and children. It is both a vehicle for and manifestation of crucial interpersonal links. In the physical sense, this is seen when the adolescent or adult's physical sexual expression is evidence of closeness to another and it also a way of achieving such closeness. In the psychological sense, sexual behavior in current relationships may be hindered by carrying the image of internalized aspects of past relationships; it may also afford a new setting for further work on them. This paper explores family aspects of sexual issues in several areas, demonstrating that when sexual dysfunction represents the distillation of a couple's relationship to their own parents, successful resolution of their own sexual relationship may be a crucial first step in rebuilding family harmony and providing a culture of intimacy for their children."} {"id": "PMID:1271478", "title": "Issues and dilemmas in sexual treatment.", "content": "Five concrete issues and dilemmas typically confronted in the practice of treatment of sexual problems are discussed. These are: (a) the issue of therapeutic values and conflict in values that may arise for the therapist; (b) the phenomenon of the desperation of the impotent male and its relationship to coping techniques and cultural expectations; (c) masturbation as a development stage in sexual responsiveness, based on evidence from historical, cross-cultural, human, and animal studies and clinical practice; (d) the positive aspects of the self-concept of nonorgasmic women that may serve as resistance to sexual responsiveness; and (e) a specific value conflict for women therapists that is a reflection of the change in values promoted by the women's movement.", "contents": "Issues and dilemmas in sexual treatment. Five concrete issues and dilemmas typically confronted in the practice of treatment of sexual problems are discussed. These are: (a) the issue of therapeutic values and conflict in values that may arise for the therapist; (b) the phenomenon of the desperation of the impotent male and its relationship to coping techniques and cultural expectations; (c) masturbation as a development stage in sexual responsiveness, based on evidence from historical, cross-cultural, human, and animal studies and clinical practice; (d) the positive aspects of the self-concept of nonorgasmic women that may serve as resistance to sexual responsiveness; and (e) a specific value conflict for women therapists that is a reflection of the change in values promoted by the women's movement."} {"id": "PMID:1271479", "title": "New data about female sexual response.", "content": "This paper reports on a 195-subject pilot study of female sexual responses. The questionnaire used in the study is described, and the data obtained are discussed and integrated with established research and theory. Discussion focuses on the relatively low frequency with which women actually experience orgasm in sexual relations and the need to understand the reasons for this phenomenon. The concept of the normality of this varied capacity for orgasm is presented in contrast to the usual tendency to evaluate female responses by male standards. Several sexual patterns and different types of orgasms in the female are identified, and the relationship between the type of responses perceived and various other factors is discussed. Responses indicated that, on the average, the strength and degree of gratification provided by an orgasm is not related to the method of induction or to the subjective localization of the pulsating sensations.", "contents": "New data about female sexual response. This paper reports on a 195-subject pilot study of female sexual responses. The questionnaire used in the study is described, and the data obtained are discussed and integrated with established research and theory. Discussion focuses on the relatively low frequency with which women actually experience orgasm in sexual relations and the need to understand the reasons for this phenomenon. The concept of the normality of this varied capacity for orgasm is presented in contrast to the usual tendency to evaluate female responses by male standards. Several sexual patterns and different types of orgasms in the female are identified, and the relationship between the type of responses perceived and various other factors is discussed. Responses indicated that, on the average, the strength and degree of gratification provided by an orgasm is not related to the method of induction or to the subjective localization of the pulsating sensations."} {"id": "PMID:1271480", "title": "Persistence, planning, patience, and prevention: aspects of sex education in medicine.", "content": "This paper emphasizes the rapid response of American medical schools to the absence of sex education in their curricula, which has led to diversity of design, strategy, and evaluation of human sexuality courses. It further points out that most such courses are inadequate to teach physicians knowledge and skills that will be required when they leave medical school. Major areas of resistance to full implementation of comprehensive sex education programs are cited, with one method outlined to overcome institutional resistance. The authors cite case examples of the variety of sexual conflicts that become accessible in students and faculty as a result of such instruction. They suggest that groups of persons who are sexually knowledgeable and possess counseling skills in sex therapy could greatly improve sex education in the medical institution.", "contents": "Persistence, planning, patience, and prevention: aspects of sex education in medicine. This paper emphasizes the rapid response of American medical schools to the absence of sex education in their curricula, which has led to diversity of design, strategy, and evaluation of human sexuality courses. It further points out that most such courses are inadequate to teach physicians knowledge and skills that will be required when they leave medical school. Major areas of resistance to full implementation of comprehensive sex education programs are cited, with one method outlined to overcome institutional resistance. The authors cite case examples of the variety of sexual conflicts that become accessible in students and faculty as a result of such instruction. They suggest that groups of persons who are sexually knowledgeable and possess counseling skills in sex therapy could greatly improve sex education in the medical institution."} {"id": "PMID:1271481", "title": "Sex education for adolescents and their families.", "content": "This paper describes a unique, 2-day experiential program in sex education for adolescents and their families. The program is adapted from a similar teaching program for medical students and is a highly focused, intense emotional experience wherein participants are presented, via a multimedia approach, with a planned sequence of explicit sexual material on all areas of human sexuality. During the program, six small group sessions with family members in separate groups enable participants to share impressions and examine anxieties aroused by the presentations. The entire process is monitored by evaluative instruments and questionnaires. Results of the data support the hypothesis that communication is possible between generations, and assists rather than inhibits the development of an adult identity.", "contents": "Sex education for adolescents and their families. This paper describes a unique, 2-day experiential program in sex education for adolescents and their families. The program is adapted from a similar teaching program for medical students and is a highly focused, intense emotional experience wherein participants are presented, via a multimedia approach, with a planned sequence of explicit sexual material on all areas of human sexuality. During the program, six small group sessions with family members in separate groups enable participants to share impressions and examine anxieties aroused by the presentations. The entire process is monitored by evaluative instruments and questionnaires. Results of the data support the hypothesis that communication is possible between generations, and assists rather than inhibits the development of an adult identity."} {"id": "PMID:1271482", "title": "Accumulation of calcium in kidney and decrease of calcium in serum of rats treated with tin chloride.", "content": "Effect of tin on the kidney calcium and serum calcium concentration was studied in rats intraperitoneally administered with tin chloride. The calcium concentration in kidney was significantly increased by administration of tin (1.0 mg/100 g), and this increase was dose dependent. A significant increase in the level of kidney calcium was not exhibited by the administration of zinc, manganese, or lead. The increased calcium after the administration of tin predominantly accumulated in the cortex of kidney. The administration of tin did not show a significant alteration of sodium and potassium concentration in the kidney. The level of serum calcium was significantly decreased by the administration of tin (2.0 mg/100 g), and this reduction was dose dependent. The decrease of serum calcium by the administration of tin was associated with the accumulation of calcium in the kidney by treatment with tin.", "contents": "Accumulation of calcium in kidney and decrease of calcium in serum of rats treated with tin chloride. Effect of tin on the kidney calcium and serum calcium concentration was studied in rats intraperitoneally administered with tin chloride. The calcium concentration in kidney was significantly increased by administration of tin (1.0 mg/100 g), and this increase was dose dependent. A significant increase in the level of kidney calcium was not exhibited by the administration of zinc, manganese, or lead. The increased calcium after the administration of tin predominantly accumulated in the cortex of kidney. The administration of tin did not show a significant alteration of sodium and potassium concentration in the kidney. The level of serum calcium was significantly decreased by the administration of tin (2.0 mg/100 g), and this reduction was dose dependent. The decrease of serum calcium by the administration of tin was associated with the accumulation of calcium in the kidney by treatment with tin."} {"id": "PMID:1271483", "title": "Metabolism of a new herbicide, tebuthiuron (1-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]- 1,3-dimethylurea), in mouse, rat, rabbit, dog, duck, and fish.", "content": "Orally dosed tebuthiuron was readily absorbed in mice, rats, rabbits, dogs, and ducks. The compound was extensively metabolized and the metabolites were rapidly excreted in the urine of mice, rats, rabbits, and dogs and in the mixture of urine and feces in ducks. The major metabolites of tebuthiuron were formed by N-demthylation of the substituted urea side chain in each species examined, including fish. Oxidation of the dimethylethyl group occurred in mice, rats, dogs, rabbits, and ducks. The N-demethylation reaction at the 3-position of the urea proceded through an N-hydroxymethyl intermediate. No accumulation of tebuthiuron or its metabolites was observed in the animals, a finding consistent with the low order of toxicity observed in other studies.", "contents": "Metabolism of a new herbicide, tebuthiuron (1-[5-(1,1-dimethylethyl)-1,3,4-thiadiazol-2-yl]- 1,3-dimethylurea), in mouse, rat, rabbit, dog, duck, and fish. Orally dosed tebuthiuron was readily absorbed in mice, rats, rabbits, dogs, and ducks. The compound was extensively metabolized and the metabolites were rapidly excreted in the urine of mice, rats, rabbits, and dogs and in the mixture of urine and feces in ducks. The major metabolites of tebuthiuron were formed by N-demthylation of the substituted urea side chain in each species examined, including fish. Oxidation of the dimethylethyl group occurred in mice, rats, dogs, rabbits, and ducks. The N-demethylation reaction at the 3-position of the urea proceded through an N-hydroxymethyl intermediate. No accumulation of tebuthiuron or its metabolites was observed in the animals, a finding consistent with the low order of toxicity observed in other studies."} {"id": "PMID:1271484", "title": "Toxicity of delta9 -tetrahydrocannabinol (THC) administered subcutaneously for 13 days to female rabbits.", "content": "Delta9- Tetrahydrocannabinol (THC) was administered subcutaneously to female New Zealand white strain rabbits for 13 days. The animals were randomly divided into six groups of five animals each of which consisted of untreated controls, vehicle (undiluted propylene glycol)-treated, and THC treatment at dose levels of 100, 30, 10, and 3 mg/kg/day. All animals survived for the duration of the study. The THC-treated rabbits did not gain significant body weight which seems to be due to a decreased food consumption. There were some variations in various hematologic values, but they all were within the normal range for our laboratory. Blood chemistry evaluations showed decreased serum levels of potassium, glucose, blood urea nitrogen, alkaline phosphatase, and albumin/globulin (A/G) ratio and an increase in cholesterol levels of all treated animals. A significant increase in billirubin values was noted in the animsls of the 3- and 10-mg/kg groups. The injection site in the skin of the THC-treated rabbits showed signs of local irritation (erythema and subcutaneous abscesses). There was a reduction in absolute and percent of body weight of the liver and absolute weight of the lungs of the treated animals. However, no histopathologic alterations were observed. It may be concluded that THC treatment subcutaneously for 13 days in rabbits up to a dose level of 100 mg/kg/day did not produce any significant toxicity, except anorexia and some local dermal irritation.", "contents": "Toxicity of delta9 -tetrahydrocannabinol (THC) administered subcutaneously for 13 days to female rabbits. Delta9- Tetrahydrocannabinol (THC) was administered subcutaneously to female New Zealand white strain rabbits for 13 days. The animals were randomly divided into six groups of five animals each of which consisted of untreated controls, vehicle (undiluted propylene glycol)-treated, and THC treatment at dose levels of 100, 30, 10, and 3 mg/kg/day. All animals survived for the duration of the study. The THC-treated rabbits did not gain significant body weight which seems to be due to a decreased food consumption. There were some variations in various hematologic values, but they all were within the normal range for our laboratory. Blood chemistry evaluations showed decreased serum levels of potassium, glucose, blood urea nitrogen, alkaline phosphatase, and albumin/globulin (A/G) ratio and an increase in cholesterol levels of all treated animals. A significant increase in billirubin values was noted in the animsls of the 3- and 10-mg/kg groups. The injection site in the skin of the THC-treated rabbits showed signs of local irritation (erythema and subcutaneous abscesses). There was a reduction in absolute and percent of body weight of the liver and absolute weight of the lungs of the treated animals. However, no histopathologic alterations were observed. It may be concluded that THC treatment subcutaneously for 13 days in rabbits up to a dose level of 100 mg/kg/day did not produce any significant toxicity, except anorexia and some local dermal irritation."} {"id": "PMID:1271485", "title": "Lymphatic tissue response in chickens treated with tri-o-tolyl phosphate.", "content": "Indices of immunologic response elicited by tri-o-tolyl phosphate (TOTP) in chickens were investigated. Histopathologic evaluation of lymphatic organs (spleen, cecal tonsil, bursa of Fabricius) and selected immuno-related visceral organs containing lymphatic infiltrations (liver, kidney, duodenum, pancreas) was conducted. Liver and spleen showed a consistent and definite increase of diffuse lymphatic tissue in TOTP-treated animals. Total plasma protein levels of treated animals were increased from 7 to 20% over 4-14 days after TOTP administration. A similar increased pattern was noted in gamma-globulin:albumin ratios of the treated group. The data suggested stimulation of immunologic response in chickens treated with TOTP.", "contents": "Lymphatic tissue response in chickens treated with tri-o-tolyl phosphate. Indices of immunologic response elicited by tri-o-tolyl phosphate (TOTP) in chickens were investigated. Histopathologic evaluation of lymphatic organs (spleen, cecal tonsil, bursa of Fabricius) and selected immuno-related visceral organs containing lymphatic infiltrations (liver, kidney, duodenum, pancreas) was conducted. Liver and spleen showed a consistent and definite increase of diffuse lymphatic tissue in TOTP-treated animals. Total plasma protein levels of treated animals were increased from 7 to 20% over 4-14 days after TOTP administration. A similar increased pattern was noted in gamma-globulin:albumin ratios of the treated group. The data suggested stimulation of immunologic response in chickens treated with TOTP."} {"id": "PMID:1271486", "title": "Effects of 1,1,1-trichloroethane administered by different routes and in different solvents on barbiturate hypnosis and metabolism in mice.", "content": "A 24-hr inhalation of 1,1,1-tricholoroethane (methylchloroform), 3,000 ppm, reduced pentobarbital hypnosis and increased hexobarbitaloxidation by the 9,000 x g liver supernatant fraction in male mice. On the other hand, an ip injection of methylchloroform, l ml/kg, increased the duration of pentobarbital hypnosis and reduced hexobarbital metabolism by the liver microsomal enzymes. The potentioating effect of methylchloroform on pentobarbital hypnosis as diminished when it was diluted with olive oil, but was markedly enhanced when diluted with dimethysusoxide (DMSO) before injection. Three local applications of methylchloroform )1:1 dilution with DMSO) had an effect similar to that of inhalation on pentobarbital hypnosis.", "contents": "Effects of 1,1,1-trichloroethane administered by different routes and in different solvents on barbiturate hypnosis and metabolism in mice. A 24-hr inhalation of 1,1,1-tricholoroethane (methylchloroform), 3,000 ppm, reduced pentobarbital hypnosis and increased hexobarbitaloxidation by the 9,000 x g liver supernatant fraction in male mice. On the other hand, an ip injection of methylchloroform, l ml/kg, increased the duration of pentobarbital hypnosis and reduced hexobarbital metabolism by the liver microsomal enzymes. The potentioating effect of methylchloroform on pentobarbital hypnosis as diminished when it was diluted with olive oil, but was markedly enhanced when diluted with dimethysusoxide (DMSO) before injection. Three local applications of methylchloroform )1:1 dilution with DMSO) had an effect similar to that of inhalation on pentobarbital hypnosis."} {"id": "PMID:1271487", "title": "Lack of effect of dietary diethylstilbestrol on reproductive performance.", "content": "Groups of male or female mice were pretreated for 2 wk and 1 wk, respectively, with flesh (liver or muscle) diets prepared from steers. In one experiment diethylstilbestrol (DES) was added to the diet at 0.5 or 5.0 ppb. In a second experiment diets prepared from DES-implanted steer flesh (liver or muscle) were fed. Tissues used in the control diet and DES-added diets were from DES-free steers. The animals were allowed to mate and diets continued until the first litter was delivered. Increasing DES levels in either liver or muscle diets or flesh from DES-implanted steers resulted in no significant differences either in litter size or in the number of fertile male or female mice between the control group and experimental groups. The offspring from each litter were mated and showed no significant difference in their reproductive performance. No abnormalities were noted in any offspring.", "contents": "Lack of effect of dietary diethylstilbestrol on reproductive performance. Groups of male or female mice were pretreated for 2 wk and 1 wk, respectively, with flesh (liver or muscle) diets prepared from steers. In one experiment diethylstilbestrol (DES) was added to the diet at 0.5 or 5.0 ppb. In a second experiment diets prepared from DES-implanted steer flesh (liver or muscle) were fed. Tissues used in the control diet and DES-added diets were from DES-free steers. The animals were allowed to mate and diets continued until the first litter was delivered. Increasing DES levels in either liver or muscle diets or flesh from DES-implanted steers resulted in no significant differences either in litter size or in the number of fertile male or female mice between the control group and experimental groups. The offspring from each litter were mated and showed no significant difference in their reproductive performance. No abnormalities were noted in any offspring."} {"id": "PMID:1271488", "title": "Deldrin and parathion interaction in the prostate and liver of the mouse.", "content": "The oral administration of dieldrin (1.25 mg/kg daily x 5 or 10) and/or parathion (5.2, 2.6, or 1.3 mg/kg daily x 5 or u0) caused significant alterations in the metabolism of [1,2-3H]testosterone by the anterior prostate gland and by the hepatic microsomal enzyme system in the mouse. A 5-day parathion treatment followed by another 5-day treatment with dieldrin led to significant increases in the levels of [3H]androstanediol a [3H]androstenedione formed by the prostate gland in vitro. Dieldrin alone, dieldrin plus parathion, or dieldrin administration followed by parathion treatment caused significant reductions in the levels of [3H]androstenedione formed by hepatic microsomal enzymes. Concomitantly, significant increases were observed in hepatic 7alpha-and 6beta-testosterone hydroxylase activities in animals treated with parathion followed by dieldrin administration. The present findings revealed that the administration of parathion or dieldrin leads to changes in the metabolism of male sex hormones in mouse liver and sex accessory organs. In addition, the simultaneous administration of parathion and dieldrin leads to an interaction that can alter the biologic effects of either compound.", "contents": "Deldrin and parathion interaction in the prostate and liver of the mouse. The oral administration of dieldrin (1.25 mg/kg daily x 5 or 10) and/or parathion (5.2, 2.6, or 1.3 mg/kg daily x 5 or u0) caused significant alterations in the metabolism of [1,2-3H]testosterone by the anterior prostate gland and by the hepatic microsomal enzyme system in the mouse. A 5-day parathion treatment followed by another 5-day treatment with dieldrin led to significant increases in the levels of [3H]androstanediol a [3H]androstenedione formed by the prostate gland in vitro. Dieldrin alone, dieldrin plus parathion, or dieldrin administration followed by parathion treatment caused significant reductions in the levels of [3H]androstenedione formed by hepatic microsomal enzymes. Concomitantly, significant increases were observed in hepatic 7alpha-and 6beta-testosterone hydroxylase activities in animals treated with parathion followed by dieldrin administration. The present findings revealed that the administration of parathion or dieldrin leads to changes in the metabolism of male sex hormones in mouse liver and sex accessory organs. In addition, the simultaneous administration of parathion and dieldrin leads to an interaction that can alter the biologic effects of either compound."} {"id": "PMID:1271489", "title": "Toxicology of vindesine (desacetyl vinblastine amide) in mice, rats, and dogs.", "content": "Comparative acute intravenous toxicity studies of vinblastine sulfate (VLB), vincristine sulfate (VCR), and vindesine in mice and rats indicated that vindesine was more toxic than VLB and less toxic than VCR. Rats were able to tolerate larger repeated doses of vindesine than dogs. Rats given intravenous doses totaling 0.15 mg/kg-wk vindesine for 3 months developed no remarkable signs of toxicity. Doses of 0.3 mg/kg-wk or greater produced anorexia, depressed blood cell counts, atrophic intestinal mucosa, inhibition of spermatogenesis, extramedullary hematopoiesis, and infections. Dogs were given total weekly intravenous doses of 0.04, 0.08, 0.1, or 0.16 mg/kg vindesine for 3 months. The only observed effect in the two lower dose groups was inhibition of spermatogenesis. Groups receiving 0.1 or 0.16 mg/kg developed leukopenia, slight erythropenia, inhibition of spermatogenesis, focal skeletal muscle degeneration, elevated lactic dehydrogenase, and an increase in bone marrow myeloid: erythroid ratio. No evidence of functional or structural changes in neural tissues was found. The above effects are common to animals given VCR at lower doses and for a shorter test period. It is therefore concluded that vindesine is less toxic in animals than VCR.", "contents": "Toxicology of vindesine (desacetyl vinblastine amide) in mice, rats, and dogs. Comparative acute intravenous toxicity studies of vinblastine sulfate (VLB), vincristine sulfate (VCR), and vindesine in mice and rats indicated that vindesine was more toxic than VLB and less toxic than VCR. Rats were able to tolerate larger repeated doses of vindesine than dogs. Rats given intravenous doses totaling 0.15 mg/kg-wk vindesine for 3 months developed no remarkable signs of toxicity. Doses of 0.3 mg/kg-wk or greater produced anorexia, depressed blood cell counts, atrophic intestinal mucosa, inhibition of spermatogenesis, extramedullary hematopoiesis, and infections. Dogs were given total weekly intravenous doses of 0.04, 0.08, 0.1, or 0.16 mg/kg vindesine for 3 months. The only observed effect in the two lower dose groups was inhibition of spermatogenesis. Groups receiving 0.1 or 0.16 mg/kg developed leukopenia, slight erythropenia, inhibition of spermatogenesis, focal skeletal muscle degeneration, elevated lactic dehydrogenase, and an increase in bone marrow myeloid: erythroid ratio. No evidence of functional or structural changes in neural tissues was found. The above effects are common to animals given VCR at lower doses and for a shorter test period. It is therefore concluded that vindesine is less toxic in animals than VCR."} {"id": "PMID:1271490", "title": "Teratological evaluation of FD&C Red no. 2 -a collaborative government-industry study. II. FDA's study.", "content": "Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, and ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio-Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.", "contents": "Teratological evaluation of FD&C Red no. 2 -a collaborative government-industry study. II. FDA's study. Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, and ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio-Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible."} {"id": "PMID:1271491", "title": "Teratological evaluation of FD&C Red no. 2-a collaborative government -industry study. III. IBT's study.", "content": "Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No.2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel stran rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River stain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.", "contents": "Teratological evaluation of FD&C Red no. 2-a collaborative government -industry study. III. IBT's study. Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No.2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel stran rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River stain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible."} {"id": "PMID:1271492", "title": "Teratological evaluation of FD&C Red No. 2-a collaborative government -industry study. IV. NCTR's study.", "content": "Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA),Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.", "contents": "Teratological evaluation of FD&C Red No. 2-a collaborative government -industry study. IV. NCTR's study. Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, an ad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA),Industrial Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities or other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible."} {"id": "PMID:1271493", "title": "Teratological evaluation of FD&C Red no. 2-a collaborative government -industry study. V. Combined findings and discussion.", "content": "Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, anad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrail Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities of other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible.", "contents": "Teratological evaluation of FD&C Red no. 2-a collaborative government -industry study. V. Combined findings and discussion. Because of recent studies indicating possible embryolethality and teratogenicity of FD&C Red No. 2, anad hoc committee was convened by the Food and Drug Administration to consider these questions. The committee suggested a collaborative study by three laboratories [Food and Drug Administration (FDA), Industrail Bio- Test Laboratories (IBT), and National Center for Toxicological Research (NCTR)] in which Red No. 2 was given at 200 mg/kg body weight, by gavage during days 0-19, 6-15, or 7-9 of gestation. FD&C Red No. 2 was also given at the same dose level via water bottle. Appropriate controls were utilized. FDA used Osborne-Mendel strain rats, IBT used Charles River, and NCTR used both strains. No significant increases in skeletal or visceral abnormalities were seen. No significant increase in resorptions was seen in the Osborne-Mendel strain, but the Charles River strain at IBT showed a significant increase in litters with two or more resorptions after dams had been given 200 mg/kg at 0-19 days of gestation. The NCTR study on the Charles River strain also showed an increase in the same parameter for the same dose level and in addition showed a significant increase in the percentage of resorptions per litter. It was concluded that because of the inherent variation and the absence of an increase in abnormalities of other indications of embryotoxicity, there is reason to doubt that this effect is either biologically significant or reproducible."} {"id": "PMID:1271494", "title": "The pathophysiology of acute electric injuries.", "content": "Results of the present investigation indicate that an electric burn is simply a thermal injury. The tissue damage associated with an electric injury occurs when electric energy is converted to thermal energy or heat. An electric burn is self limiting: once the current arcs, no further skin and muscle damage is possible because amperage falls to zero. Tissue temperature is the critical factor in determining the magnitude of tissue injury before the current arcs. With the exception of skin resistance, resistances of individual tissues seem not relevant to amount of tissue damage in electric injuries. Living tissue acts as a volume conductor; once skin resistance has been overcome all internal tissue resistance, with the exception of bone, is negligible to current flow. In the present study the volume of tissue traversed by the electric current was more closely related to the extent of tissue injury than the internal resistance of the individual tissues. Muscle injury occurred at the time of initial thermal insult and progressive or de novo muscle necrosis was not seen in this model.", "contents": "The pathophysiology of acute electric injuries. Results of the present investigation indicate that an electric burn is simply a thermal injury. The tissue damage associated with an electric injury occurs when electric energy is converted to thermal energy or heat. An electric burn is self limiting: once the current arcs, no further skin and muscle damage is possible because amperage falls to zero. Tissue temperature is the critical factor in determining the magnitude of tissue injury before the current arcs. With the exception of skin resistance, resistances of individual tissues seem not relevant to amount of tissue damage in electric injuries. Living tissue acts as a volume conductor; once skin resistance has been overcome all internal tissue resistance, with the exception of bone, is negligible to current flow. In the present study the volume of tissue traversed by the electric current was more closely related to the extent of tissue injury than the internal resistance of the individual tissues. Muscle injury occurred at the time of initial thermal insult and progressive or de novo muscle necrosis was not seen in this model."} {"id": "PMID:1271495", "title": "Fat emboli syndrome.", "content": "A review of the medical records of 30 patients with major trauma was undertaken. One third had fat emboli syndrome characterized by hypoxemia, confusion, and petechiae. Fluid balance was similar for all patients in the study. Hematologic indices had no prognostic value in identifying patients who were to become symptomatic from fat embolization. The serum albumin concentrations were significantly lower in the symptomatic group. The free fatty acid binding capacity of albumin is discussed.", "contents": "Fat emboli syndrome. A review of the medical records of 30 patients with major trauma was undertaken. One third had fat emboli syndrome characterized by hypoxemia, confusion, and petechiae. Fluid balance was similar for all patients in the study. Hematologic indices had no prognostic value in identifying patients who were to become symptomatic from fat embolization. The serum albumin concentrations were significantly lower in the symptomatic group. The free fatty acid binding capacity of albumin is discussed."} {"id": "PMID:1271496", "title": "A comparative study of four materials in local burn care in rabbit model.", "content": "In rabbits, a second-degree burn model with partial tangenitial excision of necrotic tissue was used to compare four dressing materials for effectiveness of promoting wound healing. The time of complete epithelization of the 2 X 4 cm large defect, changes in wound area, adherence of the dressings to the wound, and histology of the wound bed and dressings were measured. Dressings were changed twice weekly. Experiments showed that as a local dressing for burns, non-laminated collagen sponge was significantly better than pigskin or xeroform. Infection did not occur under it. It was very adherent to the burn wound and was actively permeated by inflammatory cells. This factor allowed early debridement of the wound. Effective debridement was probably responsible for the shorter healing time shown. Laminated collagen sponge was the poorest of the four dressings tested.", "contents": "A comparative study of four materials in local burn care in rabbit model. In rabbits, a second-degree burn model with partial tangenitial excision of necrotic tissue was used to compare four dressing materials for effectiveness of promoting wound healing. The time of complete epithelization of the 2 X 4 cm large defect, changes in wound area, adherence of the dressings to the wound, and histology of the wound bed and dressings were measured. Dressings were changed twice weekly. Experiments showed that as a local dressing for burns, non-laminated collagen sponge was significantly better than pigskin or xeroform. Infection did not occur under it. It was very adherent to the burn wound and was actively permeated by inflammatory cells. This factor allowed early debridement of the wound. Effective debridement was probably responsible for the shorter healing time shown. Laminated collagen sponge was the poorest of the four dressings tested."} {"id": "PMID:1271497", "title": "Ninety-eight penetrating vascular injuries: a review of a two and one-half year experience.", "content": "In a review of 55 patients with 98 penetrating vascular injuries over more than 2 years (most were gunshot wounds), the mortality rate was 46% in patients with intra-abdominal vascular injuries and 7% in those with extra-abdominal injuries. There were no major amputations. One patient had two fingers amputated.", "contents": "Ninety-eight penetrating vascular injuries: a review of a two and one-half year experience. In a review of 55 patients with 98 penetrating vascular injuries over more than 2 years (most were gunshot wounds), the mortality rate was 46% in patients with intra-abdominal vascular injuries and 7% in those with extra-abdominal injuries. There were no major amputations. One patient had two fingers amputated."} {"id": "PMID:1271498", "title": "Fracture healing in rats treated with diphenylhydantoin (Dilantin).", "content": "Fibula fractures were surgically made in mature male rats. Experimental animals received 4 mg/kg body weight of DPH (Dilantin) injected intraperitoneally, and equivalent volumes of sterile saline were injected intraperitoneally in controls. Fracture healing was assessed by a histologic method 5, 10, 15, 20, 25, and 30 days following the fracture. Thirty days following the injury, the DPH-treated animals showed a statistically significant increased rate of union. A comparison in trends of fracture healing for experimental and control animals showed similar enhancement of fracture healing in the experimental animals throughout the entire observation period.", "contents": "Fracture healing in rats treated with diphenylhydantoin (Dilantin). Fibula fractures were surgically made in mature male rats. Experimental animals received 4 mg/kg body weight of DPH (Dilantin) injected intraperitoneally, and equivalent volumes of sterile saline were injected intraperitoneally in controls. Fracture healing was assessed by a histologic method 5, 10, 15, 20, 25, and 30 days following the fracture. Thirty days following the injury, the DPH-treated animals showed a statistically significant increased rate of union. A comparison in trends of fracture healing for experimental and control animals showed similar enhancement of fracture healing in the experimental animals throughout the entire observation period."} {"id": "PMID:1271499", "title": "Femoral shaft fractures in brain-injured children.", "content": "Thirty-nine head injured, initially comatose children with 44 femoral shaft fractures were treated by various methods. Thirty-two eventually ambulated. Tibial skeletal traction and skin traction were ineffective methods of management. Internal fixation or distal femoral traction are advised.", "contents": "Femoral shaft fractures in brain-injured children. Thirty-nine head injured, initially comatose children with 44 femoral shaft fractures were treated by various methods. Thirty-two eventually ambulated. Tibial skeletal traction and skin traction were ineffective methods of management. Internal fixation or distal femoral traction are advised."} {"id": "PMID:1271500", "title": "Trauma or treatment? The role of intermittent traction in the treatment of cervical soft tissue injuries.", "content": "Neurophysiology does not provide a satisfactory theory which explains the phenomenon of muscular \"spasm\" which is said to be present in the neck following soft-tissue injury. Lacking knowledge as to whether long continued intermittent traction--ranging from 10 pounds to total body weight pull--is therapeutic or traumatic, such treatments nevertheless are prescribed in physiotherapy departments and at home for months. They are believed to be non-physiological and irrational and, in the author's opinon, represent the persistence of several medical myths associated with the \"rear-end\" collision. The question is moot whether the intractable complaints following such injuries are not caused, in large part, by the repeated traumas to muscles, disks, and joints produced by strong intermittent distraction. Experimental anatomical studies also argue against the hopes expressed in favor of such treatment, namely: to relieve spasm and/or traumatic fibro-myositis (?), to enlarge the neural foramina and relieve \"radiculitis,\" and to hasten recovery by means of a conjectured internal massage.", "contents": "Trauma or treatment? The role of intermittent traction in the treatment of cervical soft tissue injuries. Neurophysiology does not provide a satisfactory theory which explains the phenomenon of muscular \"spasm\" which is said to be present in the neck following soft-tissue injury. Lacking knowledge as to whether long continued intermittent traction--ranging from 10 pounds to total body weight pull--is therapeutic or traumatic, such treatments nevertheless are prescribed in physiotherapy departments and at home for months. They are believed to be non-physiological and irrational and, in the author's opinon, represent the persistence of several medical myths associated with the \"rear-end\" collision. The question is moot whether the intractable complaints following such injuries are not caused, in large part, by the repeated traumas to muscles, disks, and joints produced by strong intermittent distraction. Experimental anatomical studies also argue against the hopes expressed in favor of such treatment, namely: to relieve spasm and/or traumatic fibro-myositis (?), to enlarge the neural foramina and relieve \"radiculitis,\" and to hasten recovery by means of a conjectured internal massage."} {"id": "PMID:1271501", "title": "The hazard of the unrestrained occupant.", "content": "A review of 208 cases involving injuries sustained by vehicle occupants was extracted from the computer storage at the Highway Safety Research Institute, University of Michigan, Ann Arbor. In addition, 157 new car crashes investigated by the authors were separately analyzed. Data analysis indicates injuries are sustained by direct occupant-to-occupant contact and by one occupant forcing another into or against one or more interior car structures. All body areas can be involved in this previously unreported injury mechanism, with the upper portion of the body more susceptibel to injury. Case histories from field accident investigations document a variety of these injury mechanisms.", "contents": "The hazard of the unrestrained occupant. A review of 208 cases involving injuries sustained by vehicle occupants was extracted from the computer storage at the Highway Safety Research Institute, University of Michigan, Ann Arbor. In addition, 157 new car crashes investigated by the authors were separately analyzed. Data analysis indicates injuries are sustained by direct occupant-to-occupant contact and by one occupant forcing another into or against one or more interior car structures. All body areas can be involved in this previously unreported injury mechanism, with the upper portion of the body more susceptibel to injury. Case histories from field accident investigations document a variety of these injury mechanisms."} {"id": "PMID:1271502", "title": "Roll seat belt induced injury of the duodenum.", "content": "A case of duodenal rupture with a roll three-point seatbelt is described. It is apparently the seventh reported case of duodenal rupture in safety belt users. A female driver fell asleep, and her car went off the road, rolling forward in a ditch, slowing slightly, and then came to a sudden stop. The rupture was unusual: on the first part of duodenum, intraperitoneal, and longitudinal. The rupture mechanism is discussed, and the deficiencies of the roll seatbelt pointed out in accidents like the one described.", "contents": "Roll seat belt induced injury of the duodenum. A case of duodenal rupture with a roll three-point seatbelt is described. It is apparently the seventh reported case of duodenal rupture in safety belt users. A female driver fell asleep, and her car went off the road, rolling forward in a ditch, slowing slightly, and then came to a sudden stop. The rupture was unusual: on the first part of duodenum, intraperitoneal, and longitudinal. The rupture mechanism is discussed, and the deficiencies of the roll seatbelt pointed out in accidents like the one described."} {"id": "PMID:1271503", "title": "Acute leukopenia as an allergic reaction to silver sulfadiazine in burn patients.", "content": "Of 68 burn patients at the University of Wisoncsin Burn Center treated with silver sulfadiazine cream over 2 years, two (about 3%) developed fever and marked leukopenia. The symptoms disappeared 1-2 days after discontinuation of the cream. The two cases are described and possible mechanisms of allergic response to this agent are discussed.", "contents": "Acute leukopenia as an allergic reaction to silver sulfadiazine in burn patients. Of 68 burn patients at the University of Wisoncsin Burn Center treated with silver sulfadiazine cream over 2 years, two (about 3%) developed fever and marked leukopenia. The symptoms disappeared 1-2 days after discontinuation of the cream. The two cases are described and possible mechanisms of allergic response to this agent are discussed."} {"id": "PMID:1271504", "title": "Dislocation of the talonavicular joint: case report.", "content": "Dislocation of the talonavicular joint is rare, caused by severe abduction or adduction of the forefoot. Proper reduction is necessary to avoid equinovarus deformity, ankylosis, or degenerative arthritis. A case of talonavicular dislocation with fracture of the head of the talus in a 52-year old woman is reported, with delayed treatment by open reduction using Kirschner wires and casting for 7 weeks. This patient is successfully employed as a waitress 2 years postinjury.", "contents": "Dislocation of the talonavicular joint: case report. Dislocation of the talonavicular joint is rare, caused by severe abduction or adduction of the forefoot. Proper reduction is necessary to avoid equinovarus deformity, ankylosis, or degenerative arthritis. A case of talonavicular dislocation with fracture of the head of the talus in a 52-year old woman is reported, with delayed treatment by open reduction using Kirschner wires and casting for 7 weeks. This patient is successfully employed as a waitress 2 years postinjury."} {"id": "PMID:1271505", "title": "Unstable hemipelvic fractures with internal rotation displacement.", "content": "Two cases of unstable hemipelvic fractures with internal rotation displacement successfully treated by outward (external lateral) rotation and continuous skeletal traction by wires passed through the crest of the ilium are described. X-rays show both patients before and 2 years after treatment.", "contents": "Unstable hemipelvic fractures with internal rotation displacement. Two cases of unstable hemipelvic fractures with internal rotation displacement successfully treated by outward (external lateral) rotation and continuous skeletal traction by wires passed through the crest of the ilium are described. X-rays show both patients before and 2 years after treatment."} {"id": "PMID:1271506", "title": "Gastric necrosis from blunt abdominal trauma.", "content": "Two patients with ischemic necrosis of a portion of the gastric wall resulting from blunt abdominal trauma are reported. This gastric injury results from avulsion of the mesentery from the injured area or from a shearing force. Careful inspection of the stomach during exploration is emphasized and gastrotomy advocated if injury is suspected. Treatment consists of resection of the ischemic portion of the stomach.", "contents": "Gastric necrosis from blunt abdominal trauma. Two patients with ischemic necrosis of a portion of the gastric wall resulting from blunt abdominal trauma are reported. This gastric injury results from avulsion of the mesentery from the injured area or from a shearing force. Careful inspection of the stomach during exploration is emphasized and gastrotomy advocated if injury is suspected. Treatment consists of resection of the ischemic portion of the stomach."} {"id": "PMID:1271507", "title": "Stab wound causing mesenteric-portal arteriovenous fistula: an unusual case with a spontaneous closure.", "content": "A case of spontaneous closure of a mesenteric-portal arteriovenous fistula secondary to a stab wound is described. Although a variety of clinical complications can result from such fistulae, it is not always possible to perform an immediate closure of such lesions. The patient described was unable because of his condition to undergo surgical repair of his fistula: when readmitted after 2 months the fistula had closed and the artery was normal.", "contents": "Stab wound causing mesenteric-portal arteriovenous fistula: an unusual case with a spontaneous closure. A case of spontaneous closure of a mesenteric-portal arteriovenous fistula secondary to a stab wound is described. Although a variety of clinical complications can result from such fistulae, it is not always possible to perform an immediate closure of such lesions. The patient described was unable because of his condition to undergo surgical repair of his fistula: when readmitted after 2 months the fistula had closed and the artery was normal."} {"id": "PMID:1271508", "title": "Lacerations of the lacrimal apparatus, parotid duct, and facial nerve: case report.", "content": "Diagnosis and surgical treatment of a male patient with severe facial lacerations involving the lacrimal duct, parotid duct, and buccal branch of facial nerve are presented. Careful wound care and localization of severed nerves and ducts, and repair under microscope are emphasized.", "contents": "Lacerations of the lacrimal apparatus, parotid duct, and facial nerve: case report. Diagnosis and surgical treatment of a male patient with severe facial lacerations involving the lacrimal duct, parotid duct, and buccal branch of facial nerve are presented. Careful wound care and localization of severed nerves and ducts, and repair under microscope are emphasized."} {"id": "PMID:1271510", "title": "The Montenegro reaction in guinea pigs infected by Leishmania enriettii and the effect of antigens prepared from various Leishmania isolates.", "content": "All antigens (leishmanin) prepared from nine isolates of Leishmania gave positive skin tests in guinea pigs infected with L. enriettii. However, variation in potency was observed and ascribed to batch variation. It is recommended that biological testing of leishmanin is considered before use in field surveys or as an aid to clinical diagnosis.", "contents": "The Montenegro reaction in guinea pigs infected by Leishmania enriettii and the effect of antigens prepared from various Leishmania isolates. All antigens (leishmanin) prepared from nine isolates of Leishmania gave positive skin tests in guinea pigs infected with L. enriettii. However, variation in potency was observed and ascribed to batch variation. It is recommended that biological testing of leishmanin is considered before use in field surveys or as an aid to clinical diagnosis."} {"id": "PMID:1271511", "title": "Acute renal failure following hornet stings.", "content": "Reports of acute tubular necrosis following envenomation by hornets are rare. A 38-year-old farmer presented with evidence of haemolysis and acute renal failure following multiple hornet stings (Vespa orientalis). Biopsy of skin from the site of the stings showed evidence of vasculitis. Renal biopsy showed characteristic changes of acute tubular necrosis. Intravascular haemolysis due to haemolytic properties of the hornet venom was considered to be chiefly responsible for the renal lesions in this patient.", "contents": "Acute renal failure following hornet stings. Reports of acute tubular necrosis following envenomation by hornets are rare. A 38-year-old farmer presented with evidence of haemolysis and acute renal failure following multiple hornet stings (Vespa orientalis). Biopsy of skin from the site of the stings showed evidence of vasculitis. Renal biopsy showed characteristic changes of acute tubular necrosis. Intravascular haemolysis due to haemolytic properties of the hornet venom was considered to be chiefly responsible for the renal lesions in this patient."} {"id": "PMID:1271518", "title": "Synthesis of the adenovirus-coded DNA binding protein in infected cells.", "content": "Synthesis of the 75K (75K indicates a moleculatr weight of 70,000 to 75,000) DNA binding protein, an early virus-coded protein in adenovirus 2-infected KB cells, and its regulation were studied by using a radioimmune precipitation inhibition assay. The protein was first detected at 4 h postinfection and accumulated at an expoential rate. An arrest of further synthesis (accumulation) was observed at 10 to 11 h postinfection, coinciding with the onset of synthesis of late virion proteins. In contrast, when the infected cells were treated with 25 mug of arabinosyl cytosine per ml to block viral DNA replication, the synthesis of 75K protein did not cease but continue for up to 36 h postinfection. The synthesis of 75K protein in cells after release from a cycloheximide block (2 to 9 h postinfection) was analyzed. Increased amounts of early adenovirus-specific mRNA accumulate in infected cells during a cycloheximide block (Parsons and Green, 1971). However, cycloheximide treatment did not produce increased levels of 75K protein, and an abrupt arrest of 75K protein formation was again observed at the time of synthesis of late virion proteins. Partition of the 75K protein between the nuclear and cytoplasmic fractions during the course of infection was studied. The 75K protein appeared first in the cytoplasm and then in the nucleus after a slight lag. Accumulation of the 75K protein continued both in the cytoplasm and nucleus, with higher levels being found in the cytoplasm.", "contents": "Synthesis of the adenovirus-coded DNA binding protein in infected cells. Synthesis of the 75K (75K indicates a moleculatr weight of 70,000 to 75,000) DNA binding protein, an early virus-coded protein in adenovirus 2-infected KB cells, and its regulation were studied by using a radioimmune precipitation inhibition assay. The protein was first detected at 4 h postinfection and accumulated at an expoential rate. An arrest of further synthesis (accumulation) was observed at 10 to 11 h postinfection, coinciding with the onset of synthesis of late virion proteins. In contrast, when the infected cells were treated with 25 mug of arabinosyl cytosine per ml to block viral DNA replication, the synthesis of 75K protein did not cease but continue for up to 36 h postinfection. The synthesis of 75K protein in cells after release from a cycloheximide block (2 to 9 h postinfection) was analyzed. Increased amounts of early adenovirus-specific mRNA accumulate in infected cells during a cycloheximide block (Parsons and Green, 1971). However, cycloheximide treatment did not produce increased levels of 75K protein, and an abrupt arrest of 75K protein formation was again observed at the time of synthesis of late virion proteins. Partition of the 75K protein between the nuclear and cytoplasmic fractions during the course of infection was studied. The 75K protein appeared first in the cytoplasm and then in the nucleus after a slight lag. Accumulation of the 75K protein continued both in the cytoplasm and nucleus, with higher levels being found in the cytoplasm."} {"id": "PMID:1271519", "title": "Cell-free translation of influenza virus mRNA.", "content": "Cytoplasmic poly (A)-rich RNA extracted from fowl plague virus-infected cells was found to program efficiently the translation of two major peptides in the wheat germ cell-free system. These peptides have the same electrophoretic mobility, on polyacrylamide gels, as the two major virion proteins M and NP. [35S] methionine tryptic peptide analysis by one-dimensionalthin-layer ionophoresis and finger printing by two-dimensional thin-layer ionophoresis and chromatography show a high degree of similarity between the two in vitro products and the authentic viral proteins M and NP. Although virion RNA is devoid of any poly (A) sequence, it is confirmed here that the viral complementary cytoplasmic RNA contains poly (A) stretches of varying lengths. Intact purified virion was found to promote the synthesis of very low amounts of the same NP and M proteins in this cell-free system. Quantitative aspects of data would indicate that this is due to minute amounts of complementary viral RNA associated with the virion or with the virion RNA itself. In conclusion, it is shown diectly by cell-free translation of authentic viral products that the influenza virion is \"negative stranded\" (Baltimore, 1971), at least for its two major structural proteins.", "contents": "Cell-free translation of influenza virus mRNA. Cytoplasmic poly (A)-rich RNA extracted from fowl plague virus-infected cells was found to program efficiently the translation of two major peptides in the wheat germ cell-free system. These peptides have the same electrophoretic mobility, on polyacrylamide gels, as the two major virion proteins M and NP. [35S] methionine tryptic peptide analysis by one-dimensionalthin-layer ionophoresis and finger printing by two-dimensional thin-layer ionophoresis and chromatography show a high degree of similarity between the two in vitro products and the authentic viral proteins M and NP. Although virion RNA is devoid of any poly (A) sequence, it is confirmed here that the viral complementary cytoplasmic RNA contains poly (A) stretches of varying lengths. Intact purified virion was found to promote the synthesis of very low amounts of the same NP and M proteins in this cell-free system. Quantitative aspects of data would indicate that this is due to minute amounts of complementary viral RNA associated with the virion or with the virion RNA itself. In conclusion, it is shown diectly by cell-free translation of authentic viral products that the influenza virion is \"negative stranded\" (Baltimore, 1971), at least for its two major structural proteins."} {"id": "PMID:1271520", "title": "Translation of murine leukemia virus RNA in cell-free systems from animal cells.", "content": "The virion RNA of Moloney murine leukemia virus (MuLV) has been translated in eukaryotic cell-free systems derived from mouse L- and human HeLa cells. In both systems at least three polypeptides, approximately 60,000, 70,000, and 180,000 in apparent molecular weight, were formed in response to the added 35S MuLV RNA. All three polypeptides were precipitable with antiserum to detergent-disrupted MuLV. Fingerprint analysis of tryptic digests indicated that all three contain anino acid sequences in common with each other and with the major methionine-containing structural proteins of the virion.", "contents": "Translation of murine leukemia virus RNA in cell-free systems from animal cells. The virion RNA of Moloney murine leukemia virus (MuLV) has been translated in eukaryotic cell-free systems derived from mouse L- and human HeLa cells. In both systems at least three polypeptides, approximately 60,000, 70,000, and 180,000 in apparent molecular weight, were formed in response to the added 35S MuLV RNA. All three polypeptides were precipitable with antiserum to detergent-disrupted MuLV. Fingerprint analysis of tryptic digests indicated that all three contain anino acid sequences in common with each other and with the major methionine-containing structural proteins of the virion."} {"id": "PMID:1271521", "title": "High-voltage electron microscope study of the release of vaccinia virus from whole cells.", "content": "High-voltage (1,000-kV) electron microscope examination of whole BSC-1 cells infected with vaccinia virus at different times after infection revealed the presence of increasing numbers of virions no longer confined to factories but situated along the cell periphery of monolayer cells. Stereoscopic images showed each virus enclosed within a membrane-like component of the host cell cytoplasm. Viruses within factories appeared to lack similar enclosures. Cytochalasin B, but not vinblastine, caused the enclosures to disrupt. Vaccinia viruses were observed to escape the host cell individually from the tips of microvillie and within packets of cytoplasm. Observations suggest that the intracellular movement and release of vaccinia virus utilize a host cell cytoplasmic network that involves microfilaments for stability.", "contents": "High-voltage electron microscope study of the release of vaccinia virus from whole cells. High-voltage (1,000-kV) electron microscope examination of whole BSC-1 cells infected with vaccinia virus at different times after infection revealed the presence of increasing numbers of virions no longer confined to factories but situated along the cell periphery of monolayer cells. Stereoscopic images showed each virus enclosed within a membrane-like component of the host cell cytoplasm. Viruses within factories appeared to lack similar enclosures. Cytochalasin B, but not vinblastine, caused the enclosures to disrupt. Vaccinia viruses were observed to escape the host cell individually from the tips of microvillie and within packets of cytoplasm. Observations suggest that the intracellular movement and release of vaccinia virus utilize a host cell cytoplasmic network that involves microfilaments for stability."} {"id": "PMID:1271522", "title": "Multiple structures of adeno-associated virus DNA: analysis of terminally labeled molecules with endonuclease R-Hae III.", "content": "The double-stranded form of adeno-associated virus (AAV) DNA has about 20 sites sensitive to endonuclease R.Hae III from Haemophilus aegypitus; the fragments produced fall into about 13 size classes, 8 of which contain single fragments. The location of the Hae III-produced AAV fragments relative to the three EcoR1 fragments was determined. Using revised figures for the molecular weights of the Hae III cleavage products of phiX174 replicative form DNA, we calculated that AAV DNA contains about 4,000 nucleotides. After Hae III digestiion of duplex DNA terminally labeled with 32P using polynucleotide kinase, the majority of fragments containing a 5' 32P label were about 40 nucleotides in length, and fragments of similar size were generated from each end, suggesting that the Hae site closest to the end is within the terminal repetition. Two more-slowly-migrating cleavage products also bore 5' 32P end label. These three terminally labeled species were also generated from single-stranded AAV DNA by digestion with Hae III, and evidence that one may have a nonlinear (\"rabbit-ear\") structure is presented. The predominant 5' terminal base was identified as thymine for both the plus and minus strands of AAV. Single-stranded AAV molecules could not be efficiently covalently circularized by incubation with polynucleotide ligase or ligase plus T4 DNA polymerase.", "contents": "Multiple structures of adeno-associated virus DNA: analysis of terminally labeled molecules with endonuclease R-Hae III. The double-stranded form of adeno-associated virus (AAV) DNA has about 20 sites sensitive to endonuclease R.Hae III from Haemophilus aegypitus; the fragments produced fall into about 13 size classes, 8 of which contain single fragments. The location of the Hae III-produced AAV fragments relative to the three EcoR1 fragments was determined. Using revised figures for the molecular weights of the Hae III cleavage products of phiX174 replicative form DNA, we calculated that AAV DNA contains about 4,000 nucleotides. After Hae III digestiion of duplex DNA terminally labeled with 32P using polynucleotide kinase, the majority of fragments containing a 5' 32P label were about 40 nucleotides in length, and fragments of similar size were generated from each end, suggesting that the Hae site closest to the end is within the terminal repetition. Two more-slowly-migrating cleavage products also bore 5' 32P end label. These three terminally labeled species were also generated from single-stranded AAV DNA by digestion with Hae III, and evidence that one may have a nonlinear (\"rabbit-ear\") structure is presented. The predominant 5' terminal base was identified as thymine for both the plus and minus strands of AAV. Single-stranded AAV molecules could not be efficiently covalently circularized by incubation with polynucleotide ligase or ligase plus T4 DNA polymerase."} {"id": "PMID:1271523", "title": "DNA-protein complex in circular DNA from Bacillus bacteriophage GA-1.", "content": "DNA prepared from bacteriophage GA-1 contains circular DNA molecules, which are converted to linear molecules by treatment with trypsin.", "contents": "DNA-protein complex in circular DNA from Bacillus bacteriophage GA-1. DNA prepared from bacteriophage GA-1 contains circular DNA molecules, which are converted to linear molecules by treatment with trypsin."} {"id": "PMID:1271524", "title": "Method for the isolation of bacteriphage T4 mutants that produce particles with giant capsids.", "content": "An efficient procedure is described for isolating bacteriophage T4 mutants that produce particles with giant capsids. The selective parameters of the technique rely primarily on the giants' characteristic density in cesium gradients and on their resistance to UV radiation.", "contents": "Method for the isolation of bacteriphage T4 mutants that produce particles with giant capsids. An efficient procedure is described for isolating bacteriophage T4 mutants that produce particles with giant capsids. The selective parameters of the technique rely primarily on the giants' characteristic density in cesium gradients and on their resistance to UV radiation."} {"id": "PMID:1271525", "title": "Neurovirulence and induction of hydrocephalus with parental, mutant, and revertant strains of measles virus.", "content": "The relationship between neurovirulence and induction of hydrocephalus was investigated for a measles virus temperature-sensitive mutant and its revertant. The revertant regained the neurovirulence of the parental strain. At appropriate doses the parental, mutant, and revertant strains induced hydrocephalus.", "contents": "Neurovirulence and induction of hydrocephalus with parental, mutant, and revertant strains of measles virus. The relationship between neurovirulence and induction of hydrocephalus was investigated for a measles virus temperature-sensitive mutant and its revertant. The revertant regained the neurovirulence of the parental strain. At appropriate doses the parental, mutant, and revertant strains induced hydrocephalus."} {"id": "PMID:1271526", "title": "Message activity of influenza viral RNA.", "content": "The message activity of influenza virion RNA in the wheat germ cell-free protein-synthesizing system was investigated. RNA extracted from purified virions was found to direct the synthesis of a polypeptide that had the mobility of viral nucleocapsid protein on sodium dodecyl sulfate-polyacrylamide gels. Further characterization of the protein indicated it was not the nucleocapsid protein. No other polypeptides were detected. We conclude that influenza virion RNA is inactive as a template for the synthesis of virus-specific proteins.", "contents": "Message activity of influenza viral RNA. The message activity of influenza virion RNA in the wheat germ cell-free protein-synthesizing system was investigated. RNA extracted from purified virions was found to direct the synthesis of a polypeptide that had the mobility of viral nucleocapsid protein on sodium dodecyl sulfate-polyacrylamide gels. Further characterization of the protein indicated it was not the nucleocapsid protein. No other polypeptides were detected. We conclude that influenza virion RNA is inactive as a template for the synthesis of virus-specific proteins."} {"id": "PMID:1271527", "title": "Excision and duplication of su3+-transducing fragments carried by bacteriophage phi 80. I. Novel structure of phi 80sus2psu3+ DNA molecule.", "content": "DNA molecules of phi 80sus2psu3+ and phi 80dsu3+ isolated by Andoh and Ozeki (1968) were studied by the electron microscope heteroduplex method. The phi 80sus2psu3+ and phi 80dsu3+ DNA lengths were found to be 108.7 and 103.3% of the phi 80 DNA, respectively. The phi 80sus2psu3+/phi 80 heteroduplex shows an insertion loop of 8.7% of the phi 80 DNA which migrates from 7.7 to 9.7%, as measured relative to the left (0%) and right (100%) termini of the mature phi 80 DNA molecule. The region of loop migration occupies the central region of the phi 80 head gene cluster. The presence of su3+-containing Escherichia coli DNA of 6.7% phi 80 unit flanked by two homologous regions of phage DNA of 2.0% of phi 80 unit gives rise to a movable insertion loop. In phi 80dsu3+, from which phi 80sus2psu3+ was derived, 50.5% of the phi 80 DNA at the left arm was replaced by E. coli DNA containing the su3+ gene, equivalent to about 53.8% phi 80 unit in length. The phi 80sus2psu3+/phi 80dsu3+ heteroduplex appears as a double-stranded molecule that bifurcates into two clearly visible single-stranded regions, rejoins, bifurcates, and rejoins again. The middle double-stranded stretches of 6.7% phi 80 unit correspond to the E. coli DNA inserted in phi 80sus2psu3+. Therefore the transducing fragment carried by phi 80sus2psu3+ originates from the inside region of the transducing fragment of defective phage phi 80dsu3+ by at least two illegitimate recombination events.", "contents": "Excision and duplication of su3+-transducing fragments carried by bacteriophage phi 80. I. Novel structure of phi 80sus2psu3+ DNA molecule. DNA molecules of phi 80sus2psu3+ and phi 80dsu3+ isolated by Andoh and Ozeki (1968) were studied by the electron microscope heteroduplex method. The phi 80sus2psu3+ and phi 80dsu3+ DNA lengths were found to be 108.7 and 103.3% of the phi 80 DNA, respectively. The phi 80sus2psu3+/phi 80 heteroduplex shows an insertion loop of 8.7% of the phi 80 DNA which migrates from 7.7 to 9.7%, as measured relative to the left (0%) and right (100%) termini of the mature phi 80 DNA molecule. The region of loop migration occupies the central region of the phi 80 head gene cluster. The presence of su3+-containing Escherichia coli DNA of 6.7% phi 80 unit flanked by two homologous regions of phage DNA of 2.0% of phi 80 unit gives rise to a movable insertion loop. In phi 80dsu3+, from which phi 80sus2psu3+ was derived, 50.5% of the phi 80 DNA at the left arm was replaced by E. coli DNA containing the su3+ gene, equivalent to about 53.8% phi 80 unit in length. The phi 80sus2psu3+/phi 80dsu3+ heteroduplex appears as a double-stranded molecule that bifurcates into two clearly visible single-stranded regions, rejoins, bifurcates, and rejoins again. The middle double-stranded stretches of 6.7% phi 80 unit correspond to the E. coli DNA inserted in phi 80sus2psu3+. Therefore the transducing fragment carried by phi 80sus2psu3+ originates from the inside region of the transducing fragment of defective phage phi 80dsu3+ by at least two illegitimate recombination events."} {"id": "PMID:1271528", "title": "Cleavage maps of the filamentous bacteriophages M13, fd, fl, and ZJ/2.", "content": "The replicative form DNAs of bacteriophage M13, fd, f1, and ZJ/2 were found to be sensitive to cleavage by the restriction endonucleases endoR-HapII, endoR-HaeII, endoR-HaeIII, endoR-HindII, endoR-AluI, endoR-Hha, and endoR-Hinf. With respect to M13 DNA the number of cleavage sites varied from 21 for endoR-Hinf, 18 for endoR-AluI, 15 for endoR-Hha, 13 for endoR-HapII, 10 for endoR-HaeIII, 3 for endoR-HaeII, to only a single site for endoR-HindII. In contrast to M13, fd and f1, the ZJ/2 DNA molecule was not cleaved by the endoR-HindII endonuclease. No cleavage site on either phage DNA was detected for the endonucleases endoR-Hsu, endoR-EcoRI and endoR-Sma. When compared with M13 DNA, several differences were noted in the number and size of cleavage products obtained with DNA of phage fd, f1, and ZJ/2. From the results of these analyses, using the M13 enzyme cleavage maps as a reference, the endoR-HapII, endoR-HaeII, endoR-HaeIII, endoR-HindII and endoR-AluI maps of phage fd, f1, and ZJ/2 could be constructed. As is expected for very closely related phages, the enzyme cleavage patterns exhibit a high degree of homology. Phage f1 and ZJ/2 are most related since an identical pattern was obtained with seven different restriction endonucleases. Evidence is provided also that f1 is more similar to M13 than to fd. Furthermore, characteristic differences exist within the endoR-Hinf enzyme cleavage pattern of all the four phages tested. Digestion of phage DNA with this enzyme, therefore, provides a new and sensitive method of distinguishing these closely related filamentous coliphages .", "contents": "Cleavage maps of the filamentous bacteriophages M13, fd, fl, and ZJ/2. The replicative form DNAs of bacteriophage M13, fd, f1, and ZJ/2 were found to be sensitive to cleavage by the restriction endonucleases endoR-HapII, endoR-HaeII, endoR-HaeIII, endoR-HindII, endoR-AluI, endoR-Hha, and endoR-Hinf. With respect to M13 DNA the number of cleavage sites varied from 21 for endoR-Hinf, 18 for endoR-AluI, 15 for endoR-Hha, 13 for endoR-HapII, 10 for endoR-HaeIII, 3 for endoR-HaeII, to only a single site for endoR-HindII. In contrast to M13, fd and f1, the ZJ/2 DNA molecule was not cleaved by the endoR-HindII endonuclease. No cleavage site on either phage DNA was detected for the endonucleases endoR-Hsu, endoR-EcoRI and endoR-Sma. When compared with M13 DNA, several differences were noted in the number and size of cleavage products obtained with DNA of phage fd, f1, and ZJ/2. From the results of these analyses, using the M13 enzyme cleavage maps as a reference, the endoR-HapII, endoR-HaeII, endoR-HaeIII, endoR-HindII and endoR-AluI maps of phage fd, f1, and ZJ/2 could be constructed. As is expected for very closely related phages, the enzyme cleavage patterns exhibit a high degree of homology. Phage f1 and ZJ/2 are most related since an identical pattern was obtained with seven different restriction endonucleases. Evidence is provided also that f1 is more similar to M13 than to fd. Furthermore, characteristic differences exist within the endoR-Hinf enzyme cleavage pattern of all the four phages tested. Digestion of phage DNA with this enzyme, therefore, provides a new and sensitive method of distinguishing these closely related filamentous coliphages ."} {"id": "PMID:1271529", "title": "Bacteriophage and bacteriophage-like structures carried by Bacillus medusa and their effect on sporulation.", "content": "Bacillus medusa was found to carry three phages or phagelike structures named phi med-1, phi med-2, and phi med-3. phi med-1 is a minute, 25-nm-diameter particle without a tail. It was extracted from the sporulation lysate of a phi med-2-minus strain of B. medusa and purified by differential centrifugation. The nucleic acid from this structure was shown to be orcinol positive, alkali sensitive, RNase sensitive, and DNase resistant. An RNase-resistant core of nucleic acid was not found, indicating that it was single-stranded RNA. A host strain has not yet been found for phi med-1. Phage phi med-3 was induced with mitomycin C or UV light and consisted of empty heads of 57 nm in diameter, whereas phi med-2 induced with mitomycin was a phage of 60-nm head diameter and 220-nm tail length. The sporulation sequence proceeded faster in those mutants lacking phi med-2, and when the phage was reintroduced to B. medusa the extended wild-type sporulation sequence was observed. B. thuringiensis var. schwetzova was sensitive to phi med-2 and yielded small turbid plaques. B. medusa produced small numbers of phi med-2 during growth. The other phage may be produced at the same time but were not detected. Phi med-1 was found in sporulating cells by electron microscopy techniques. Its release from these was demonstrated by both electron microscopy techniques and a radioactive assay. It appears to participate in the formation of a surface layer on the parasporal inclusion of B. medusa.", "contents": "Bacteriophage and bacteriophage-like structures carried by Bacillus medusa and their effect on sporulation. Bacillus medusa was found to carry three phages or phagelike structures named phi med-1, phi med-2, and phi med-3. phi med-1 is a minute, 25-nm-diameter particle without a tail. It was extracted from the sporulation lysate of a phi med-2-minus strain of B. medusa and purified by differential centrifugation. The nucleic acid from this structure was shown to be orcinol positive, alkali sensitive, RNase sensitive, and DNase resistant. An RNase-resistant core of nucleic acid was not found, indicating that it was single-stranded RNA. A host strain has not yet been found for phi med-1. Phage phi med-3 was induced with mitomycin C or UV light and consisted of empty heads of 57 nm in diameter, whereas phi med-2 induced with mitomycin was a phage of 60-nm head diameter and 220-nm tail length. The sporulation sequence proceeded faster in those mutants lacking phi med-2, and when the phage was reintroduced to B. medusa the extended wild-type sporulation sequence was observed. B. thuringiensis var. schwetzova was sensitive to phi med-2 and yielded small turbid plaques. B. medusa produced small numbers of phi med-2 during growth. The other phage may be produced at the same time but were not detected. Phi med-1 was found in sporulating cells by electron microscopy techniques. Its release from these was demonstrated by both electron microscopy techniques and a radioactive assay. It appears to participate in the formation of a surface layer on the parasporal inclusion of B. medusa."} {"id": "PMID:1271530", "title": "Effect of 5-bromodeoxyuridine on vaccinia virus-induced polypeptide synthesis: selective inhibition of the synthesis of some post-replicative polypeptides.", "content": "The effect of 5-bromodeoxyuridine (BrdU) on vaccinia virus-induced polypeptide synthesis in BSC-1 cells has been investigated. Most virus-induced pre- and post-replicative polypeptides were synthesized in concentrations of 5-bromodeoxyuridine that inhibited virus growth. The synthesis of a few post-replicative polypeptides, however, was severely inhibited under these conditions; included in this group was the precursor of a major core component, polypeptide P4b. A delay in the switch-off of pre-replicative polypeptide synthesis and in the onset of post-replicative polypeptide synthesis was also observed. The significance of these observations is discussed.", "contents": "Effect of 5-bromodeoxyuridine on vaccinia virus-induced polypeptide synthesis: selective inhibition of the synthesis of some post-replicative polypeptides. The effect of 5-bromodeoxyuridine (BrdU) on vaccinia virus-induced polypeptide synthesis in BSC-1 cells has been investigated. Most virus-induced pre- and post-replicative polypeptides were synthesized in concentrations of 5-bromodeoxyuridine that inhibited virus growth. The synthesis of a few post-replicative polypeptides, however, was severely inhibited under these conditions; included in this group was the precursor of a major core component, polypeptide P4b. A delay in the switch-off of pre-replicative polypeptide synthesis and in the onset of post-replicative polypeptide synthesis was also observed. The significance of these observations is discussed."} {"id": "PMID:1271531", "title": "Infectious center assay for complementation and recombination between mutant of reovirus.", "content": "An infectious center assay has been developed to measure recombination and complementation in L cells mixedly infected with ts mutants of reovirus. The mutants studied so far fall into complementation groups that correspond to the recombination groups previously defined by other laboratories (B. N. Fields, 1971; B. N. Filds and W. K. Joklik, 1969).", "contents": "Infectious center assay for complementation and recombination between mutant of reovirus. An infectious center assay has been developed to measure recombination and complementation in L cells mixedly infected with ts mutants of reovirus. The mutants studied so far fall into complementation groups that correspond to the recombination groups previously defined by other laboratories (B. N. Fields, 1971; B. N. Filds and W. K. Joklik, 1969)."} {"id": "PMID:1271532", "title": "Isolation and preliminary characterization of temperature-sensitive mutants of Newcastle disease virus.", "content": "Temperature-sensitive (ts) mutants of Newcastle disease virus have been isolated and characterized genetically (complementation), biochemically (RNA synthesis) and biologically (fusion from within and hemadsorption). Fifteen of these mutants have been divided into five complementation groups. Groups A (five mutants) and E (one mutant) are ts for RNA synthesis (RNA-) as well as for the other functions. Group B contains four RNA+ mutants of which one is ts for fusion, one for hemadsorption and two for neither function. Group C contains one RNA+ mutant which is a poor cell fuser. Group D contains two RNA+ mutants which are ts for fusion. In addition, two noncomplementing mutants (group BC) fail to complement both group B and group C mutants while exhibiting complementation with mutants in groups A, D, and E.", "contents": "Isolation and preliminary characterization of temperature-sensitive mutants of Newcastle disease virus. Temperature-sensitive (ts) mutants of Newcastle disease virus have been isolated and characterized genetically (complementation), biochemically (RNA synthesis) and biologically (fusion from within and hemadsorption). Fifteen of these mutants have been divided into five complementation groups. Groups A (five mutants) and E (one mutant) are ts for RNA synthesis (RNA-) as well as for the other functions. Group B contains four RNA+ mutants of which one is ts for fusion, one for hemadsorption and two for neither function. Group C contains one RNA+ mutant which is a poor cell fuser. Group D contains two RNA+ mutants which are ts for fusion. In addition, two noncomplementing mutants (group BC) fail to complement both group B and group C mutants while exhibiting complementation with mutants in groups A, D, and E."} {"id": "PMID:1271533", "title": "Absence of interparental recombination in multiplicity reconstitution from incomplete bacteriophage T4 genomes.", "content": "Interparental recombination between injected T4 DNA molecules is indetectable for incomplete petite phages (carrying a terminally deficient genome and therefore unable to circularize) as well as for genetically complete phages. The nonvialbe petite phages can individually replicate their DNA repeatedly, and they aso undergo multiplicity reconstitution, producing complete phages, provided that a host bacterium is infected by several petite particles that carry genetically complementary segments of DNA. The formation of complete phages in multiplicity reconstitution must be due to recombination among incomplete progeny fragments, i.e., partial replicas of the T4 genomes. It evidently does not result from interparental recombination. To test for interparental recombination, light bacteria (containing no bromouracil) were simultaneously infected in light medium with light radioactive phage in minority (usually less than one per cell) and heavy (bromouracil-labeled) phage in majority (usually about nine per cell). Any interparental recombination should, under these circumstances of infection, head to movement of the radioactive label of the minority light phage DNA to a position of higher density. That possibility was not observed.", "contents": "Absence of interparental recombination in multiplicity reconstitution from incomplete bacteriophage T4 genomes. Interparental recombination between injected T4 DNA molecules is indetectable for incomplete petite phages (carrying a terminally deficient genome and therefore unable to circularize) as well as for genetically complete phages. The nonvialbe petite phages can individually replicate their DNA repeatedly, and they aso undergo multiplicity reconstitution, producing complete phages, provided that a host bacterium is infected by several petite particles that carry genetically complementary segments of DNA. The formation of complete phages in multiplicity reconstitution must be due to recombination among incomplete progeny fragments, i.e., partial replicas of the T4 genomes. It evidently does not result from interparental recombination. To test for interparental recombination, light bacteria (containing no bromouracil) were simultaneously infected in light medium with light radioactive phage in minority (usually less than one per cell) and heavy (bromouracil-labeled) phage in majority (usually about nine per cell). Any interparental recombination should, under these circumstances of infection, head to movement of the radioactive label of the minority light phage DNA to a position of higher density. That possibility was not observed."} {"id": "PMID:1271534", "title": "Identification of gene products required for in vitro formation of the internal peptides of bacteriophage T4.", "content": "In vitro formation of both bacteriophage T4 internal peptides (II and VII) from preexisting precursor protein was shown to require the product of T4 gene 21. The proteolytic factor was detectable in extracts of cells infected with certain phage mutants blocked in early steps of head assembly but could not be demonstrated in extracts of T4 wild-type infected cells. This finding suggests that the proteolytic factor is inactivated during normal phage assembly. The product of T4 gene 22 appears to be the precursor of peptide VII but not of peptide II.", "contents": "Identification of gene products required for in vitro formation of the internal peptides of bacteriophage T4. In vitro formation of both bacteriophage T4 internal peptides (II and VII) from preexisting precursor protein was shown to require the product of T4 gene 21. The proteolytic factor was detectable in extracts of cells infected with certain phage mutants blocked in early steps of head assembly but could not be demonstrated in extracts of T4 wild-type infected cells. This finding suggests that the proteolytic factor is inactivated during normal phage assembly. The product of T4 gene 22 appears to be the precursor of peptide VII but not of peptide II."} {"id": "PMID:1271535", "title": "Replication of mycoplasmavirus MVL51. IV. Inhibition of viral synthesis by rifampin.", "content": "The effect of rifampin on the replication of MVL51, a bullet-shaped mycoplasmavirus with single-stranded circular DNA of molecular weight 2 X 10(6), has been examined in a rifampin-resistant host cell. Rifampin does not block the early steps in MVL51 infection but does decrease the total amount of parental viral DNA taken up. The single-stranded parental viral DNA that enters the cell is found in membrane-associated, double-stranded DNA replicative forms I and II. Rifampin had no significant effect on the synthesis of progeny viral DNA RFI and RFII early in infection and SSI (single-stranded progeny viral chromosomes) later in infection. The rifampin block in virus synthesis was found to be in the step converting SSI into assembled virions. Rifampin was shown to affect the synthesis of virus-specific RNA, Which suggests that viral transcription is necessary for virion assembly.", "contents": "Replication of mycoplasmavirus MVL51. IV. Inhibition of viral synthesis by rifampin. The effect of rifampin on the replication of MVL51, a bullet-shaped mycoplasmavirus with single-stranded circular DNA of molecular weight 2 X 10(6), has been examined in a rifampin-resistant host cell. Rifampin does not block the early steps in MVL51 infection but does decrease the total amount of parental viral DNA taken up. The single-stranded parental viral DNA that enters the cell is found in membrane-associated, double-stranded DNA replicative forms I and II. Rifampin had no significant effect on the synthesis of progeny viral DNA RFI and RFII early in infection and SSI (single-stranded progeny viral chromosomes) later in infection. The rifampin block in virus synthesis was found to be in the step converting SSI into assembled virions. Rifampin was shown to affect the synthesis of virus-specific RNA, Which suggests that viral transcription is necessary for virion assembly."} {"id": "PMID:1271536", "title": "Analysis of radiohippuran renogram by subtraction of extrarenal radioactivity.", "content": "A method is presented for the simple, non-computerized analysis of the radiohippuran renogram by subtraction of the extrarenal radioactivity as monitored simultaneously by a detector centered over the manubrium sterni. This method requires the application of a calibration factor, relating the level of radioactivity recorded by the sternal detector to that over each kidney area at the end point of the phase of initial rise on each side separately. The results in 15 normal individuals showed a narrow range of values, indicating a high degree of resolution. Verification of the basis of this method of analysis was obtained by accounting for all of the counting rate as extrarenal sources in the tracings of nephrectomized subjects. A further advantage is that the tracing recorded by the sternal detector may be used to calculate renal blood flow.", "contents": "Analysis of radiohippuran renogram by subtraction of extrarenal radioactivity. A method is presented for the simple, non-computerized analysis of the radiohippuran renogram by subtraction of the extrarenal radioactivity as monitored simultaneously by a detector centered over the manubrium sterni. This method requires the application of a calibration factor, relating the level of radioactivity recorded by the sternal detector to that over each kidney area at the end point of the phase of initial rise on each side separately. The results in 15 normal individuals showed a narrow range of values, indicating a high degree of resolution. Verification of the basis of this method of analysis was obtained by accounting for all of the counting rate as extrarenal sources in the tracings of nephrectomized subjects. A further advantage is that the tracing recorded by the sternal detector may be used to calculate renal blood flow."} {"id": "PMID:1271537", "title": "Renal papillary necrosis in sickle cell hemoglobinopathies.", "content": "Approximately 65 per cent of patients with clinical manifestations of S-hemoglobinopathies show urographically demonstrable changes of renal papillary necrosis, regardless of the presence of urinary symptoms. With a more precise excretory urographic technique these changes can be diagnosed with greater accuracy without the need for sophisticated equipment. Excretory urography should be performed routinely in the evaluation of all patients with manifestations of S-hemoglobinopathy in order to diagnose papillary necrosis before the onset of urological symptoms.", "contents": "Renal papillary necrosis in sickle cell hemoglobinopathies. Approximately 65 per cent of patients with clinical manifestations of S-hemoglobinopathies show urographically demonstrable changes of renal papillary necrosis, regardless of the presence of urinary symptoms. With a more precise excretory urographic technique these changes can be diagnosed with greater accuracy without the need for sophisticated equipment. Excretory urography should be performed routinely in the evaluation of all patients with manifestations of S-hemoglobinopathy in order to diagnose papillary necrosis before the onset of urological symptoms."} {"id": "PMID:1271538", "title": "Extensive nephrolithotomy in previously operated solitary kidneys.", "content": "The surgical management of 2 patients with large dendritic calculi in previously operated solitary kidneys is presented. Complete nephrolithotomy was accomplished in situ using the anatropic nephrotomy technique of Smith and Boyce. Postoperatively a circle tube nephrostomy was used. The surgical management as described is recommended as an alternative to extracorporeal nephrolithotomy with autotransplantation or simple nephrectomy and dialysis.", "contents": "Extensive nephrolithotomy in previously operated solitary kidneys. The surgical management of 2 patients with large dendritic calculi in previously operated solitary kidneys is presented. Complete nephrolithotomy was accomplished in situ using the anatropic nephrotomy technique of Smith and Boyce. Postoperatively a circle tube nephrostomy was used. The surgical management as described is recommended as an alternative to extracorporeal nephrolithotomy with autotransplantation or simple nephrectomy and dialysis."} {"id": "PMID:1271539", "title": "The case for a more aggressive approach to staghorn stones.", "content": "The treat to the patient and kidney of leaving a large staghorn stone in situ in 60 cases is compared to the risk of operative removal in 125 cases. The over-all mortality rate in patients treated conservatively was 28 per cent, carcinoma developing in 4 cases and a life-threatening pyonephrosis in 16. Of patients treated by removal of the stone the mortality rate was 7.2 per cent (during 10 years of observation) and stones recurred in 21 cases. These studies refute the notion of the silent staghorn calculus and demonstrate that operative removal is safer for the patient and kidney.", "contents": "The case for a more aggressive approach to staghorn stones. The treat to the patient and kidney of leaving a large staghorn stone in situ in 60 cases is compared to the risk of operative removal in 125 cases. The over-all mortality rate in patients treated conservatively was 28 per cent, carcinoma developing in 4 cases and a life-threatening pyonephrosis in 16. Of patients treated by removal of the stone the mortality rate was 7.2 per cent (during 10 years of observation) and stones recurred in 21 cases. These studies refute the notion of the silent staghorn calculus and demonstrate that operative removal is safer for the patient and kidney."} {"id": "PMID:1271540", "title": "Urinary tuberculosis: a review of 44 cases treated since 1963.", "content": "We are reporting on a decade of experinece with cases of renal tuberculosis treated at a large tuberculosis hospital. Most patients were men less than 50 years old. The most frequent symptoms were dysuria, back or flank pain, nocturia and hematuria. Physical examinations were generally normal and hypertension was not seen. Most patients had acid urinary pH, pyuria and/or hematuria. Excretory urograms were abnormal in 86 per cent of the cases, the most common finding being preserved function but calicectasis or abscess. Most patients had abnormal chest x-rays and nearly half of them had coexisting, active pulmonary or miliary tuberculosis. Tuberculin tests were positive in 85 per cent of the cases. In our experience urinary tuberculosis was almost always responsive to multi-drug chemotherapy, even in patients with a non-functioning, tuberculous kidney. An asymptomatic, non-functioning kidney need not be removed, provided documentation of urine culture conversion is obtained and a prolonged period of multi-drug chemotherapy is completed.", "contents": "Urinary tuberculosis: a review of 44 cases treated since 1963. We are reporting on a decade of experinece with cases of renal tuberculosis treated at a large tuberculosis hospital. Most patients were men less than 50 years old. The most frequent symptoms were dysuria, back or flank pain, nocturia and hematuria. Physical examinations were generally normal and hypertension was not seen. Most patients had acid urinary pH, pyuria and/or hematuria. Excretory urograms were abnormal in 86 per cent of the cases, the most common finding being preserved function but calicectasis or abscess. Most patients had abnormal chest x-rays and nearly half of them had coexisting, active pulmonary or miliary tuberculosis. Tuberculin tests were positive in 85 per cent of the cases. In our experience urinary tuberculosis was almost always responsive to multi-drug chemotherapy, even in patients with a non-functioning, tuberculous kidney. An asymptomatic, non-functioning kidney need not be removed, provided documentation of urine culture conversion is obtained and a prolonged period of multi-drug chemotherapy is completed."} {"id": "PMID:1271541", "title": "Clinical comparison between vascular and avascular renal cell carcinoma.", "content": "Of 72 patients with renal cell carcinoma 19 were found to have an angiographic avascular neoplasm. These avascular tumors have a lower incidence of vein and capsule invasion than vascular tumors. Among these avascular cancers papillary adenocarcinoma was the predominant histologic pattern. Patients with papillary tumors seem to have a lower clinical stage and increased survival rate than patients with non-papillary tumors.", "contents": "Clinical comparison between vascular and avascular renal cell carcinoma. Of 72 patients with renal cell carcinoma 19 were found to have an angiographic avascular neoplasm. These avascular tumors have a lower incidence of vein and capsule invasion than vascular tumors. Among these avascular cancers papillary adenocarcinoma was the predominant histologic pattern. Patients with papillary tumors seem to have a lower clinical stage and increased survival rate than patients with non-papillary tumors."} {"id": "PMID:1271542", "title": "Retroperitoneal teratoma: historical review.", "content": "A case of retroperitoneal teratoma in an unusual location is presented. The tumor occurred in the right iliac fossa of a 17-year-old girl and proved fatal within 18 months, despite a seemingly adequate initial operation. The literature on the subject has been reviewed from an historical perspective.", "contents": "Retroperitoneal teratoma: historical review. A case of retroperitoneal teratoma in an unusual location is presented. The tumor occurred in the right iliac fossa of a 17-year-old girl and proved fatal within 18 months, despite a seemingly adequate initial operation. The literature on the subject has been reviewed from an historical perspective."} {"id": "PMID:1271543", "title": "Retroperitoneal fat necrosis producing ureteral obstruction.", "content": "We present 3 cases of a rare syndrome of extrinsic ureteral obstruction produced by retroperitoneal fat necrosis and compare the medical records and histopathology to 19 cases of classic idiopathic retroperitoneal fibrosis. Clinical similarities include average age of onset in the fourth and fifth decades, male preponderance, abdominal or back pain as the presenting symptom, elevation of the blood urea concentration prior to diagnosis and tendency toward bilateral involvement. Histologically, the 2 conditions were different. Retroperitoneal fat necrosis is characterized by coalescence of fat cells into fat cysts bordered by foreign body giant cell granulomas, foam cells, light chronic inflammatory infiltrate and unimpressive fibrosis. The microscopic pathology of idiopathic retroperitoneal fibrosis is dominated by densely collagenized fibrous tissue of varying cellularity without evidence of fat necrosis. Of the 3 cases of retroperitoneal fat necrosis 2 featured prior ischiorectal abscesses and this is considered in a discussion of the etiology of this unusual cause of ureteral compression.", "contents": "Retroperitoneal fat necrosis producing ureteral obstruction. We present 3 cases of a rare syndrome of extrinsic ureteral obstruction produced by retroperitoneal fat necrosis and compare the medical records and histopathology to 19 cases of classic idiopathic retroperitoneal fibrosis. Clinical similarities include average age of onset in the fourth and fifth decades, male preponderance, abdominal or back pain as the presenting symptom, elevation of the blood urea concentration prior to diagnosis and tendency toward bilateral involvement. Histologically, the 2 conditions were different. Retroperitoneal fat necrosis is characterized by coalescence of fat cells into fat cysts bordered by foreign body giant cell granulomas, foam cells, light chronic inflammatory infiltrate and unimpressive fibrosis. The microscopic pathology of idiopathic retroperitoneal fibrosis is dominated by densely collagenized fibrous tissue of varying cellularity without evidence of fat necrosis. Of the 3 cases of retroperitoneal fat necrosis 2 featured prior ischiorectal abscesses and this is considered in a discussion of the etiology of this unusual cause of ureteral compression."} {"id": "PMID:1271544", "title": "Condyloma acuminatum of the bladder.", "content": "Condyloma acuminatum in the bladder of 2 patients on immunosuppressive therapy after kidney transplantation is described. The successful treatment was transurethral electroresection and coagulation. We do not recommend radical operations in cases of condyloma acuminatum. Resected specimens should be examined pathologically to exclude papillary epithelial tumors.", "contents": "Condyloma acuminatum of the bladder. Condyloma acuminatum in the bladder of 2 patients on immunosuppressive therapy after kidney transplantation is described. The successful treatment was transurethral electroresection and coagulation. We do not recommend radical operations in cases of condyloma acuminatum. Resected specimens should be examined pathologically to exclude papillary epithelial tumors."} {"id": "PMID:1271545", "title": "Abnormal monocyte function in bladder cancer patients.", "content": "We evaluated 39 patients with various stages of bladder carcinoma to determine alterations in monocyte function. Since the monocyte plays an important role in the effector arm of the immune system defective function may explain the host's inability to destroy neoplastic cells. As a group these 39 patients demonstrated defective monocyte monocyte function. There was no correlation between tumor stage and degree of chemotactic defect. Patients with invasive carcinoma had a significant return of monocyte chemotactic response toward normal postoperatively (p less than 0.005). Monocyte function was improved also in 3 patients who received Bacillus Calmette-Guerin immunotherapy (p less than 0.05).", "contents": "Abnormal monocyte function in bladder cancer patients. We evaluated 39 patients with various stages of bladder carcinoma to determine alterations in monocyte function. Since the monocyte plays an important role in the effector arm of the immune system defective function may explain the host's inability to destroy neoplastic cells. As a group these 39 patients demonstrated defective monocyte monocyte function. There was no correlation between tumor stage and degree of chemotactic defect. Patients with invasive carcinoma had a significant return of monocyte chemotactic response toward normal postoperatively (p less than 0.005). Monocyte function was improved also in 3 patients who received Bacillus Calmette-Guerin immunotherapy (p less than 0.05)."} {"id": "PMID:1271546", "title": "Squamous cell carcinoma of the bladder.", "content": "Clinical and morphological features of 90 cases of squamous cell carcinoma of the bladder have been reviewed. The lesions were solitary in 90 per cent of the patients, developed without a history of vesical malignant disease in 82 per cent and were invasive at the time of diagnosis in all cases. Ureteral obstruction was demonstrated in 42 per cent of the group. The over-all survival rate at 5 years was only 10.6 per cent. There were 17 patients who received no therapy, all of whom were dead before 2 years. Unassisted supervoltage radiation therapy for patients with stages B2 and C lesions yielded a 5-year survival rate only 17.7 per cent. However, preoperative radiotherapy followed by simple total cystectomy and urinary diversion in a small number of patients with stages B2 and C lesions resulted in a 5-year survival rate in excess of 34 per cent. We are encouraged by this finding and believe that combination therapy warrants further clinical trial.", "contents": "Squamous cell carcinoma of the bladder. Clinical and morphological features of 90 cases of squamous cell carcinoma of the bladder have been reviewed. The lesions were solitary in 90 per cent of the patients, developed without a history of vesical malignant disease in 82 per cent and were invasive at the time of diagnosis in all cases. Ureteral obstruction was demonstrated in 42 per cent of the group. The over-all survival rate at 5 years was only 10.6 per cent. There were 17 patients who received no therapy, all of whom were dead before 2 years. Unassisted supervoltage radiation therapy for patients with stages B2 and C lesions yielded a 5-year survival rate only 17.7 per cent. However, preoperative radiotherapy followed by simple total cystectomy and urinary diversion in a small number of patients with stages B2 and C lesions resulted in a 5-year survival rate in excess of 34 per cent. We are encouraged by this finding and believe that combination therapy warrants further clinical trial."} {"id": "PMID:1271547", "title": "Sympathetic activity in the proximal urethra in patients with urinary obstruction.", "content": "The effect of 10 mg. phentolamine intravenously on the urethral pressure profile was studied in male and female patients with lower urinary tract obstruction. A significant decrease of pressure occurred along the whole length of the urethra in both sexes, including the peak pressure zone in the male patient. This zone has been traditionally attributed to the external sphincter. It was concluded that the sympathetically innervated smooth muscle exerts a certain activity along the whole length of the proximal urethra. The phentolamine test may prove to be a useful adjunct to urethral profile studies in patients with lower urinary tract obstruction.", "contents": "Sympathetic activity in the proximal urethra in patients with urinary obstruction. The effect of 10 mg. phentolamine intravenously on the urethral pressure profile was studied in male and female patients with lower urinary tract obstruction. A significant decrease of pressure occurred along the whole length of the urethra in both sexes, including the peak pressure zone in the male patient. This zone has been traditionally attributed to the external sphincter. It was concluded that the sympathetically innervated smooth muscle exerts a certain activity along the whole length of the proximal urethra. The phentolamine test may prove to be a useful adjunct to urethral profile studies in patients with lower urinary tract obstruction."} {"id": "PMID:1271548", "title": "Excision of the urogenital diaphragm: a method of repair of the completely obstructed membranous urethra.", "content": "A 15-year experience with 16 patients who suffered complete rupture of the membranous urethra and obliteration of the apex of the dislocated prostate gland is described. In 2 cases repair was done immediately after injury. The technique is described. Entrance into the perineum follows the path of the bulbous urethra rather than that of the rectal wall. After the bulbous urethra is mobilized the urogenital diaphragm is excised. The end of the bulbous urethra is approximated to the mobilized distal half of the prostate, via the shortest route between the 2 organs.", "contents": "Excision of the urogenital diaphragm: a method of repair of the completely obstructed membranous urethra. A 15-year experience with 16 patients who suffered complete rupture of the membranous urethra and obliteration of the apex of the dislocated prostate gland is described. In 2 cases repair was done immediately after injury. The technique is described. Entrance into the perineum follows the path of the bulbous urethra rather than that of the rectal wall. After the bulbous urethra is mobilized the urogenital diaphragm is excised. The end of the bulbous urethra is approximated to the mobilized distal half of the prostate, via the shortest route between the 2 organs."} {"id": "PMID:1271549", "title": "Vesical neck suspension under vision with cystotomy enhances treatment of female incontinence.", "content": "Failure to surgically correct incontinence usually results from inadequate screening of patients with hyperreflexic incontinence, improper fixation of the urethra or yielding of tissues that have supported the repair. A surgical approach is described which fixes the bladder neck to the rectus tendon and adjacent pubic periosteum, under direct vision, through a cystotomy incision. The procedure achieves good continence in more than 90 per cent of the cases. Temporary postoperative voiding dysfunction occurred in about half of the patients.", "contents": "Vesical neck suspension under vision with cystotomy enhances treatment of female incontinence. Failure to surgically correct incontinence usually results from inadequate screening of patients with hyperreflexic incontinence, improper fixation of the urethra or yielding of tissues that have supported the repair. A surgical approach is described which fixes the bladder neck to the rectus tendon and adjacent pubic periosteum, under direct vision, through a cystotomy incision. The procedure achieves good continence in more than 90 per cent of the cases. Temporary postoperative voiding dysfunction occurred in about half of the patients."} {"id": "PMID:1271550", "title": "Stress incontinence: conservative therapy with sympathomimetic drugs.", "content": "There were 77 women with mild to moderate stress urinary incontinence treated with the sympathomimetic agent, phenylpropanolamine hydrochloride, combined with chlorpheniramine maleate and isopropamide iodide in a sustained release capsule (Ornade). The majority of these patients achieved significant improvement 3 months to 3 years after beginning therapy. A trial of conservative therapy is advisable for stress incontinence, especially when symptoms are mild or when the patients are in a poor risk category. Similar management of post-prostatectomy stress incontinence in men was disappointing. However, the occasional excellent results in patients with mild symptoms appear to justify a trial of conservative therapy before considering operative intervention in this group of patients.", "contents": "Stress incontinence: conservative therapy with sympathomimetic drugs. There were 77 women with mild to moderate stress urinary incontinence treated with the sympathomimetic agent, phenylpropanolamine hydrochloride, combined with chlorpheniramine maleate and isopropamide iodide in a sustained release capsule (Ornade). The majority of these patients achieved significant improvement 3 months to 3 years after beginning therapy. A trial of conservative therapy is advisable for stress incontinence, especially when symptoms are mild or when the patients are in a poor risk category. Similar management of post-prostatectomy stress incontinence in men was disappointing. However, the occasional excellent results in patients with mild symptoms appear to justify a trial of conservative therapy before considering operative intervention in this group of patients."} {"id": "PMID:1271551", "title": "Hemihypertrophy of the human corpus cavernosum.", "content": "Hemihypertrophy of the right corpus cavernosum and its accompanying thickened tunica albuginea are responsible for the left lateral deviation in congenital curvature of the penis. Surgical correction is more predictable when the lengths of the dorsal and ventral curvatures of the corpora cavernosa are known.", "contents": "Hemihypertrophy of the human corpus cavernosum. Hemihypertrophy of the right corpus cavernosum and its accompanying thickened tunica albuginea are responsible for the left lateral deviation in congenital curvature of the penis. Surgical correction is more predictable when the lengths of the dorsal and ventral curvatures of the corpora cavernosa are known."} {"id": "PMID:1271552", "title": "Varicocle in oligospermic patients: pathophysiology and results after ligation and division of the internal spermatic vein.", "content": "We have followed for up to 32 months 51 oligospermic patients with varicoceles who underwent high ligation and division of the left spermatic vein. Of these patients 59.9 per cent had improvement in total sperm count, 47.1 per cent in sperm motility and 42.1 per cent in the morphological pattern of the spermatozoa. Pregnancies were reported by 13 patients. Improvement in sperm motility occurred first, followed by improvement in morphology. The last improvement was in total sperm count. We suggest that the observation period after a varicocele operation be restricted to 9 months, in which time about 75 per cent of the expected improvement takes place. A clinical classification for the degree of varicocele is proposed. No correlation between size of the varicocele and treatment results could be observed. A classification of sperm analysis is proposed, using a 3-digital index that might enable better comparison of sperm analysis and better communication among physicians. We could not define a specific group of oligospermic patients who might benefit more than other groups from a varicocele operation. Pathophysiological pathways leading to impaired spermatogenesis in patients with varicoceles are discussed.", "contents": "Varicocle in oligospermic patients: pathophysiology and results after ligation and division of the internal spermatic vein. We have followed for up to 32 months 51 oligospermic patients with varicoceles who underwent high ligation and division of the left spermatic vein. Of these patients 59.9 per cent had improvement in total sperm count, 47.1 per cent in sperm motility and 42.1 per cent in the morphological pattern of the spermatozoa. Pregnancies were reported by 13 patients. Improvement in sperm motility occurred first, followed by improvement in morphology. The last improvement was in total sperm count. We suggest that the observation period after a varicocele operation be restricted to 9 months, in which time about 75 per cent of the expected improvement takes place. A clinical classification for the degree of varicocele is proposed. No correlation between size of the varicocele and treatment results could be observed. A classification of sperm analysis is proposed, using a 3-digital index that might enable better comparison of sperm analysis and better communication among physicians. We could not define a specific group of oligospermic patients who might benefit more than other groups from a varicocele operation. Pathophysiological pathways leading to impaired spermatogenesis in patients with varicoceles are discussed."} {"id": "PMID:1271553", "title": "Dyssynergic vesicourethral responses during bladder rehabilitation in spinal cord injury patients: effects of suprapubic percussion, cred\u00e9 method and bethanechol chloride.", "content": "Five normal men and 70 spinal cord injury male patients underwent 100 studies with the multiple pressure recording technique, incorporating the continuous infusion principle for sphincter pressure monitoring. Gross cystosphincteric dyssynergia was noted in the majority of patients with complete upper motor neuron bladders less than 2 years in duration. Some form of synergic voiding patterns was noted, mostly in patients with incomplete upper motor neuron bladders. The external sphincter tends to be synergic in late cases of upper moto neuron bladders. Internal sphincter dyssynergia is uncommon in cases of injuries less than 2 years in duration, with the exception of patients who have autonomic dysreflexia. Bladder neck obstruction seems to be more common in late lesions secondary to global hypertrophy of the bladder. Rehabilitation maneuvers and bethanechol chloride administration may exaggerate detrusor sphincter dyssynergia and injudicious use of such procedures could be detrimental to the urinary tract.", "contents": "Dyssynergic vesicourethral responses during bladder rehabilitation in spinal cord injury patients: effects of suprapubic percussion, cred\u00e9 method and bethanechol chloride. Five normal men and 70 spinal cord injury male patients underwent 100 studies with the multiple pressure recording technique, incorporating the continuous infusion principle for sphincter pressure monitoring. Gross cystosphincteric dyssynergia was noted in the majority of patients with complete upper motor neuron bladders less than 2 years in duration. Some form of synergic voiding patterns was noted, mostly in patients with incomplete upper motor neuron bladders. The external sphincter tends to be synergic in late cases of upper moto neuron bladders. Internal sphincter dyssynergia is uncommon in cases of injuries less than 2 years in duration, with the exception of patients who have autonomic dysreflexia. Bladder neck obstruction seems to be more common in late lesions secondary to global hypertrophy of the bladder. Rehabilitation maneuvers and bethanechol chloride administration may exaggerate detrusor sphincter dyssynergia and injudicious use of such procedures could be detrimental to the urinary tract."} {"id": "PMID:1271554", "title": "Segmental renal vein renin assay and segmental nephrectomy for correction of renal hypertension.", "content": "Selective segmental renal vein catheterization was used to obtain venous blood samples for renin assay. With this technique a localized source of hypersecretion of renin was identified in 2 patients. Using samples from the main renal veins we found no significant difference in renin activity and, therefore, the etiology of the hypertension in these 2 patients would have been missed. Segmental nephrectomy resulted in a cure of the hypertension in both patients who were followed for a minimum of 14 months.", "contents": "Segmental renal vein renin assay and segmental nephrectomy for correction of renal hypertension. Selective segmental renal vein catheterization was used to obtain venous blood samples for renin assay. With this technique a localized source of hypersecretion of renin was identified in 2 patients. Using samples from the main renal veins we found no significant difference in renin activity and, therefore, the etiology of the hypertension in these 2 patients would have been missed. Segmental nephrectomy resulted in a cure of the hypertension in both patients who were followed for a minimum of 14 months."} {"id": "PMID:1271555", "title": "Ureterocalicostomy: an alternative to nephrectomy.", "content": "Ureterocalicostomy is a procedure with limited indications but with important application in the infrequent patient in whom the more desirable methods of creating unobstructed ureteropelvic drainage cannot be used. Three children are described in whom successful ureterocalicostomy was performed. The most common condition in which ureterocalicostomy has been useful is in the obstructed and scarred, intrarenal pelvis in which a classic type of ureteropyelostomy is not possible. The most important technicalconsideration seems to be sufficient amputation of the lower pole renal cortex in order to free the ureterocaliceal anastomosis from the surrounding cortical tissue. The 3 cases illustrate the difficult situations in which ureterocalicostomy may be indicated and the value of this procedure in preserving maximal renal function in children.", "contents": "Ureterocalicostomy: an alternative to nephrectomy. Ureterocalicostomy is a procedure with limited indications but with important application in the infrequent patient in whom the more desirable methods of creating unobstructed ureteropelvic drainage cannot be used. Three children are described in whom successful ureterocalicostomy was performed. The most common condition in which ureterocalicostomy has been useful is in the obstructed and scarred, intrarenal pelvis in which a classic type of ureteropyelostomy is not possible. The most important technicalconsideration seems to be sufficient amputation of the lower pole renal cortex in order to free the ureterocaliceal anastomosis from the surrounding cortical tissue. The 3 cases illustrate the difficult situations in which ureterocalicostomy may be indicated and the value of this procedure in preserving maximal renal function in children."} {"id": "PMID:1271556", "title": "Management of severe hydroureteronephrosis in infants and young children.", "content": "Loop cutaneous ureterostomy and cutaneous pyelostomy are safe and effective means of temporary diversion with few complications. Reconstructive operation is delayed until the upper urinary tract has shown maximum improvement in form and function and the patient's tolerance for elective operation has improved. Results of reconstruction may be less than optimal and serious complications may arise. However the staged approach has been shown to be safe and effective. Experience with 29 patients has led to a reassessment of the approach to patients with posterior urethral values and a stronger inclination to primary valve resection, thus avoiding many of the reconstructive procedures ultimately associated with temporary diversion. Patients with posterior urethral valves who have hydronephrotic upper urinary tracts, normal or near normal serum chemistry studies and are free of infection may receive initial valve ablation. All patients with massive hydroureteronephrosis require long-term followup to ensure preservation of renal function regardless of the approach used.", "contents": "Management of severe hydroureteronephrosis in infants and young children. Loop cutaneous ureterostomy and cutaneous pyelostomy are safe and effective means of temporary diversion with few complications. Reconstructive operation is delayed until the upper urinary tract has shown maximum improvement in form and function and the patient's tolerance for elective operation has improved. Results of reconstruction may be less than optimal and serious complications may arise. However the staged approach has been shown to be safe and effective. Experience with 29 patients has led to a reassessment of the approach to patients with posterior urethral values and a stronger inclination to primary valve resection, thus avoiding many of the reconstructive procedures ultimately associated with temporary diversion. Patients with posterior urethral valves who have hydronephrotic upper urinary tracts, normal or near normal serum chemistry studies and are free of infection may receive initial valve ablation. All patients with massive hydroureteronephrosis require long-term followup to ensure preservation of renal function regardless of the approach used."} {"id": "PMID:1271557", "title": "Ileal conduits in children at the Massachusetts General Hospital from 1955 to 1970.", "content": "The 45 ileal conduits performed on children at the Massachusetts General Hospital from 1955 to 1963 are reviewed and compared to the 45 ileal conduits performed from 1964 to 1970. Late complications involving the conduits occurred in 60 per cent of the early group and in 51 per cent of the late group. Of the renal units judged normal pyelographically preoperatively in the early group 77 per cent went on to at least some deterioration, while 62 per cent of the late group judged normal later deteriorated. Combining all renal units, 34 per cent remained unchanged, 26 per cent improved and 41 per cent showed some degree of deterioration after ileal conduit urinary diversion. The late complication and renal deterioration rates seem to increase progressively with time. There was no apparent urinary obstruction in 13 per cent of the renal units that deteriorated. Theoretical and experimental considerations indicate the reflux of infected urine as the etiology of the renal deterioration. Because of the late complications and the unacceptably high rate of renal deterioration we no longer perform ileal conduits in children. Instead every effort is made to reconstruct the urinary tract or if urinary diversion is necessary, a colon conduit with non-refluxing ureterocolonic anastomoses is performed.", "contents": "Ileal conduits in children at the Massachusetts General Hospital from 1955 to 1970. The 45 ileal conduits performed on children at the Massachusetts General Hospital from 1955 to 1963 are reviewed and compared to the 45 ileal conduits performed from 1964 to 1970. Late complications involving the conduits occurred in 60 per cent of the early group and in 51 per cent of the late group. Of the renal units judged normal pyelographically preoperatively in the early group 77 per cent went on to at least some deterioration, while 62 per cent of the late group judged normal later deteriorated. Combining all renal units, 34 per cent remained unchanged, 26 per cent improved and 41 per cent showed some degree of deterioration after ileal conduit urinary diversion. The late complication and renal deterioration rates seem to increase progressively with time. There was no apparent urinary obstruction in 13 per cent of the renal units that deteriorated. Theoretical and experimental considerations indicate the reflux of infected urine as the etiology of the renal deterioration. Because of the late complications and the unacceptably high rate of renal deterioration we no longer perform ileal conduits in children. Instead every effort is made to reconstruct the urinary tract or if urinary diversion is necessary, a colon conduit with non-refluxing ureterocolonic anastomoses is performed."} {"id": "PMID:1271558", "title": "Meconium granulomas of the tunica vaginalis.", "content": "Meconium peritonitis results from perforation of the gastrointestinal tract during fetal life. Involvement of the tunica vaginalis may be the sole presenting clinical manifestation of the disease in the unusual event of the gut perforation resolving spontaneously. In such instances radiologically detectable calcification in the abdomen and scrotum is an essential diagnostic point. A case is described in which a baby had hydroceles and bilateral intrascrotal nodules but in which calcification was radiologically undetectable, presumably owing to its having undergon resolution. The typical histology of the nodules provided the diagnosis in this otherwise clinically undiagnostic case.", "contents": "Meconium granulomas of the tunica vaginalis. Meconium peritonitis results from perforation of the gastrointestinal tract during fetal life. Involvement of the tunica vaginalis may be the sole presenting clinical manifestation of the disease in the unusual event of the gut perforation resolving spontaneously. In such instances radiologically detectable calcification in the abdomen and scrotum is an essential diagnostic point. A case is described in which a baby had hydroceles and bilateral intrascrotal nodules but in which calcification was radiologically undetectable, presumably owing to its having undergon resolution. The typical histology of the nodules provided the diagnosis in this otherwise clinically undiagnostic case."} {"id": "PMID:1271559", "title": "Long-term assessment of genital reconstruction in female pseudohermaphrodites.", "content": "The cases involving 32 women who had undergone early revision of ambiguous genitalia were reviewed 5 to 22 years postoperatively. Seven clitoridectomies, 25 clitoral recessions, 17 Y-V introitoplasties and 10 midline episiotomies were performed. There were 16 patients available for followup. The results of clitoral recessions were cosmetically and functionally satisfactory. Introital revisions done before puberty all required further revision and suggested that vaginoplasty should be deferred until after puberty.", "contents": "Long-term assessment of genital reconstruction in female pseudohermaphrodites. The cases involving 32 women who had undergone early revision of ambiguous genitalia were reviewed 5 to 22 years postoperatively. Seven clitoridectomies, 25 clitoral recessions, 17 Y-V introitoplasties and 10 midline episiotomies were performed. There were 16 patients available for followup. The results of clitoral recessions were cosmetically and functionally satisfactory. Introital revisions done before puberty all required further revision and suggested that vaginoplasty should be deferred until after puberty."} {"id": "PMID:1271560", "title": "Atypical unilateral acute pyelonephritis initially diagnosed by scinti-studies.", "content": "A patient with vague and atypical symptoms is described in whom the radionuclide dynamic and static imaging studies proved to be more useful than a preceding excretory urogram for the diagnosis of unilateral pyelonephritis.", "contents": "Atypical unilateral acute pyelonephritis initially diagnosed by scinti-studies. A patient with vague and atypical symptoms is described in whom the radionuclide dynamic and static imaging studies proved to be more useful than a preceding excretory urogram for the diagnosis of unilateral pyelonephritis."} {"id": "PMID:1271561", "title": "Emphysematous pyelonephritis.", "content": "Emphysematous pyelonephritis is a rare complication of urinary tract infection and generally occurs in patients with diabetes mellitus or urinary tract obstruction. We recently treated an 81-year-old diabetic woman with Klebsiella pneumoniae urinary tract infection and septicemia whose abdominal roentgenogram demonstrated a striking left pneumonephrogram as well as intraureteral and perirenal gas. The patient died despite intensive therapeutic efforts. Unfortunately, the prognosis for this severe necrotizing infection process remains unfavorable.", "contents": "Emphysematous pyelonephritis. Emphysematous pyelonephritis is a rare complication of urinary tract infection and generally occurs in patients with diabetes mellitus or urinary tract obstruction. We recently treated an 81-year-old diabetic woman with Klebsiella pneumoniae urinary tract infection and septicemia whose abdominal roentgenogram demonstrated a striking left pneumonephrogram as well as intraureteral and perirenal gas. The patient died despite intensive therapeutic efforts. Unfortunately, the prognosis for this severe necrotizing infection process remains unfavorable."} {"id": "PMID:1271562", "title": "A problem in hemodialysis management: fibromuscular dysplasia of radial and ulnar arteries--report of a case.", "content": "Fibromuscular dysplasia (medial type) of the radial and ulna arteries, hitherto unreported, has been demonstrated angiographically following the malfunction of an arteriovenous shunt created for dialysis. Retrograde dilatation of the segmental stenoses caused some improvement in flow. No causal relationship is claimed between fibromuscular dysplasia and the arteriovenous shunt.", "contents": "A problem in hemodialysis management: fibromuscular dysplasia of radial and ulnar arteries--report of a case. Fibromuscular dysplasia (medial type) of the radial and ulna arteries, hitherto unreported, has been demonstrated angiographically following the malfunction of an arteriovenous shunt created for dialysis. Retrograde dilatation of the segmental stenoses caused some improvement in flow. No causal relationship is claimed between fibromuscular dysplasia and the arteriovenous shunt."} {"id": "PMID:1271563", "title": "Correlation of selective angiography and pathology in cavernous hemangioma of the kidney.", "content": "Angiographic and pathologic findings are presented and correlated in a case of renal cavernous hemangioma, and considered in relation to 3 other cases published previously. A normal angiogram does not exclude a cavernous hemangioma. Those tumors with a large arterial component may be demonstrated in the arterial phase of the angiogram. A discrete tumor may show an area of hypovascularity by displacing normal renal tissue but a diffuse cavernous hemangioma is likely to yield a normal angiogram.", "contents": "Correlation of selective angiography and pathology in cavernous hemangioma of the kidney. Angiographic and pathologic findings are presented and correlated in a case of renal cavernous hemangioma, and considered in relation to 3 other cases published previously. A normal angiogram does not exclude a cavernous hemangioma. Those tumors with a large arterial component may be demonstrated in the arterial phase of the angiogram. A discrete tumor may show an area of hypovascularity by displacing normal renal tissue but a diffuse cavernous hemangioma is likely to yield a normal angiogram."} {"id": "PMID:1271564", "title": "Localized ureteral fibrosis: an unrecognized complication of radiation therapy for prostatic carcinoma.", "content": "Complications of radiation therapy for prostatic carcinoma are frequent but usually minor. A patient is described in whom localized ureteral fibrosis developed following curative radiation therapy, which subsequently required a reconstructive operation. An analogous situation regarding patients with carcinoma of the cervix is examined and possible etiologies are discussed. This complication should be recognized so that proper management can be instituted.", "contents": "Localized ureteral fibrosis: an unrecognized complication of radiation therapy for prostatic carcinoma. Complications of radiation therapy for prostatic carcinoma are frequent but usually minor. A patient is described in whom localized ureteral fibrosis developed following curative radiation therapy, which subsequently required a reconstructive operation. An analogous situation regarding patients with carcinoma of the cervix is examined and possible etiologies are discussed. This complication should be recognized so that proper management can be instituted."} {"id": "PMID:1271565", "title": "Vesicoureteral reflux complicating sterile hemorrhagic cystitis: a case report.", "content": "An unusual case of sterile hemorrhagic cystitis with bilateral vesicoureteral reflux is reported. Such a case has not been described previously.", "contents": "Vesicoureteral reflux complicating sterile hemorrhagic cystitis: a case report. An unusual case of sterile hemorrhagic cystitis with bilateral vesicoureteral reflux is reported. Such a case has not been described previously."} {"id": "PMID:1271566", "title": "Priapism: an unusual complication of parotitis without orchitis.", "content": "A 10-year-old white boy is described in whom priapism developed as a complication of parotitis without orchitis. Medical study failed to reveal any other etiology. The syndrome was assumed to be related to a mumps virus. Treatment by corpora cavernosa-spongiosum shunt relieved the acute symptoms as well as preserved the patient's ability to have an erection.", "contents": "Priapism: an unusual complication of parotitis without orchitis. A 10-year-old white boy is described in whom priapism developed as a complication of parotitis without orchitis. Medical study failed to reveal any other etiology. The syndrome was assumed to be related to a mumps virus. Treatment by corpora cavernosa-spongiosum shunt relieved the acute symptoms as well as preserved the patient's ability to have an erection."} {"id": "PMID:1271567", "title": "Melanosis of the prostate gland: report of a case with neoplastic epithelium involvement.", "content": "Prostate gland melanosis is an uncommon lesion and the precise histogenesis is unclear. Melanin may be found within melanocytes in the prostatic stroma, within prostatic epithelium and, rarely, in both locations. The stromal dendritic cell has been shown to contain premelanosomes and melanosomes suggesting primary melanin production by this cell. The melanogenic potential of prostatic epithelial cells has not yet been conclusively established. An example of prostatic melanosis is presented in which stromal and epithelial components were found. This dual distribution of melanin has been regarded as an indication that melanin in the epithelial cells results from phagocytosis of melanin from stromal melanocytes as a secondary phenomenon. Melanin pigment was identified not only within hyperplastic prostatic epithelium but also was found in the epithelial component of a well differentiated prostatic adenocarcinoma.", "contents": "Melanosis of the prostate gland: report of a case with neoplastic epithelium involvement. Prostate gland melanosis is an uncommon lesion and the precise histogenesis is unclear. Melanin may be found within melanocytes in the prostatic stroma, within prostatic epithelium and, rarely, in both locations. The stromal dendritic cell has been shown to contain premelanosomes and melanosomes suggesting primary melanin production by this cell. The melanogenic potential of prostatic epithelial cells has not yet been conclusively established. An example of prostatic melanosis is presented in which stromal and epithelial components were found. This dual distribution of melanin has been regarded as an indication that melanin in the epithelial cells results from phagocytosis of melanin from stromal melanocytes as a secondary phenomenon. Melanin pigment was identified not only within hyperplastic prostatic epithelium but also was found in the epithelial component of a well differentiated prostatic adenocarcinoma."} {"id": "PMID:1271569", "title": "3-dimensional graphic display of electrocardiograms.", "content": "We developed a new method to display a potential distribution of the heart activity on the body surface. Electrocardiograms were recorded from many points distributed regularly on the precordial region. From these electrocardiograms three-dimensional graph of potential distribution was produced by a small digital computer and displayed on the CRT. This graph continuously changes with time according to change of potential distribution like an animation. An interpolation method that we had derived took a short execution time and give a smooth approximated curve. Three-dimentional graphs of electrocardiograms were produced for healthy male subjects. From these graphs a transmission of a wave front of the ventricular activation can be seen as if the wave moves over the picture.", "contents": "3-dimensional graphic display of electrocardiograms. We developed a new method to display a potential distribution of the heart activity on the body surface. Electrocardiograms were recorded from many points distributed regularly on the precordial region. From these electrocardiograms three-dimensional graph of potential distribution was produced by a small digital computer and displayed on the CRT. This graph continuously changes with time according to change of potential distribution like an animation. An interpolation method that we had derived took a short execution time and give a smooth approximated curve. Three-dimentional graphs of electrocardiograms were produced for healthy male subjects. From these graphs a transmission of a wave front of the ventricular activation can be seen as if the wave moves over the picture."} {"id": "PMID:1271570", "title": "Alterations of the internal elastic membrane in the coeliac trunk and its branches.", "content": "Changes in the internal elastic membrane of the coeliac trunk and its branches begin in the foetus. Usually these changes increase with advancing age. The intensity of involvement varies in different arteries, localized swelling is of particular importance as a measure of atherosclerotic involvement. There is a close relationship between morphology and chemical structure.", "contents": "Alterations of the internal elastic membrane in the coeliac trunk and its branches. Changes in the internal elastic membrane of the coeliac trunk and its branches begin in the foetus. Usually these changes increase with advancing age. The intensity of involvement varies in different arteries, localized swelling is of particular importance as a measure of atherosclerotic involvement. There is a close relationship between morphology and chemical structure."} {"id": "PMID:1271571", "title": "Electrophysiological consideration on sick sinus syndrome.", "content": "1) Factors influencing abnormally prolonged Sinus Recovery Time in Sick Sinus Syndrome were investigated with a microelectrode technique. 2) Although the action of released acetyl choline was confirmed by the effect of atropine and neostigmine on the SRT, an abnormally long SRT like that in SSS was not produced by vagal stimulation in the in situ heart. 3) When the drive rate exceeded a certain value (e.g. two times the spontaneous rate in normal preparations), SA entrance block resulted in less overdrive suppression. When the SA junction is easily blocked with relatively low drive rates, the maximum SRT must be determined within a wide range of drive rates. 1) Verapamil in a concentration of 10(-7) g/ml produced an abnormal SRT suggesting that ionic derangement is one of the factors influencing SRT. 5) A preparation from an aged rabbit with an abnormal SRT revealed fibrosis and reduction in the number of SA nodal cells. The latter seems to be one of the main factors causing a reduction in the potency of the pacemaker and a prolonged SRT in SSS.", "contents": "Electrophysiological consideration on sick sinus syndrome. 1) Factors influencing abnormally prolonged Sinus Recovery Time in Sick Sinus Syndrome were investigated with a microelectrode technique. 2) Although the action of released acetyl choline was confirmed by the effect of atropine and neostigmine on the SRT, an abnormally long SRT like that in SSS was not produced by vagal stimulation in the in situ heart. 3) When the drive rate exceeded a certain value (e.g. two times the spontaneous rate in normal preparations), SA entrance block resulted in less overdrive suppression. When the SA junction is easily blocked with relatively low drive rates, the maximum SRT must be determined within a wide range of drive rates. 1) Verapamil in a concentration of 10(-7) g/ml produced an abnormal SRT suggesting that ionic derangement is one of the factors influencing SRT. 5) A preparation from an aged rabbit with an abnormal SRT revealed fibrosis and reduction in the number of SA nodal cells. The latter seems to be one of the main factors causing a reduction in the potency of the pacemaker and a prolonged SRT in SSS."} {"id": "PMID:1271572", "title": "Clinical studies on the sick sinus syndrome.", "content": "1) Overdrive suppression is clinically useful to evaluate depressed cardiac automaticity in the sick sinus syndrome. 2) His bundle electrograms revealed frequent association of atrioventricular conduction defects with the depressed automaticity in this syndrome. 3) Especially in BTS, marked intra-atrial conduction defect was observed, and this conduction defect may play a role for development of re-entrant tachycardia. 4) Pathologic changes in the sick sinus syndrome are supposed to involve the whole atrial tissues including not only the S-A nodal region but the A-V node and its approaches.", "contents": "Clinical studies on the sick sinus syndrome. 1) Overdrive suppression is clinically useful to evaluate depressed cardiac automaticity in the sick sinus syndrome. 2) His bundle electrograms revealed frequent association of atrioventricular conduction defects with the depressed automaticity in this syndrome. 3) Especially in BTS, marked intra-atrial conduction defect was observed, and this conduction defect may play a role for development of re-entrant tachycardia. 4) Pathologic changes in the sick sinus syndrome are supposed to involve the whole atrial tissues including not only the S-A nodal region but the A-V node and its approaches."} {"id": "PMID:1271574", "title": "A-V block.", "content": "In this report, 61 A-V block patients were analysed using HBE. According to the site of the block, these cases were classified into P(A)-H block, BH block H V block and mixed block. In P(A) H block group (23 cases), the permanent pacemaker implantation was not needed except for one patient with persistent heart failure due to marked bradycardia. Postmortem histology of this patient was well coincident to the results of HBE. In BH block group (18 cases), moderate number of patients were needed to have permanent pacemakers implanted (33%). RA pacing induced split H block with H-V prolongation and varied H and QRS configuration in two cases of this group. These phenomena may be well explained by the longitudinal dissociation theory. In H-V block patients, permanent pacemakers were implanted in all patients (12 cases). In this group, it is difficult to decide the exact location of block, either distal His, bifurcation or bundles, because of the difficulty to record the left or right bundle potentials in clinical practise. Finally, it is important to record the HBE in order to decide the exact site of block, and to choose the suitable therapy for A-V block patients.", "contents": "A-V block. In this report, 61 A-V block patients were analysed using HBE. According to the site of the block, these cases were classified into P(A)-H block, BH block H V block and mixed block. In P(A) H block group (23 cases), the permanent pacemaker implantation was not needed except for one patient with persistent heart failure due to marked bradycardia. Postmortem histology of this patient was well coincident to the results of HBE. In BH block group (18 cases), moderate number of patients were needed to have permanent pacemakers implanted (33%). RA pacing induced split H block with H-V prolongation and varied H and QRS configuration in two cases of this group. These phenomena may be well explained by the longitudinal dissociation theory. In H-V block patients, permanent pacemakers were implanted in all patients (12 cases). In this group, it is difficult to decide the exact location of block, either distal His, bifurcation or bundles, because of the difficulty to record the left or right bundle potentials in clinical practise. Finally, it is important to record the HBE in order to decide the exact site of block, and to choose the suitable therapy for A-V block patients."} {"id": "PMID:1271578", "title": "[A case reported of double parasystole-combined atrial and ventricular parasystole- (author's transl)].", "content": "Parasystole is an arrhythmia resulting from simultaneous activity of two independent impulse-forming foci, one of which is protected by the other. Ventricular parasystole which arises from an ectopic focus situated in ventricule is relatively common. On the contrary, supraventricular parasystole which is centered in the atria or atrioventricular junction, is extremely rare. Kaufmann and Rothberger studied first parasystole as an entity, and they reported the first case of atrial parasystole. However, the first correctly mentioned example of atrial parasystole was described by Jervell. In the previous paper, we described one observation on atrial parasystole and discussed on its consisting-mechanism. The occurrence of ventricular parasystole is not a rarity, since it has been estimated to be present once in every 1,200 electrocardiograms taken in a general hospital. In contrast, well-documented cases of atrial parasystole are exceedingly rare, and since the first case of it was reported by Kaufmann and Rothberger, only 25 cases have hitherto been reported. In the present paper is described and discussed a case of the extremely rare combination of atrial and ventricular parasystole with exit block and fusion phenomenon...", "contents": "[A case reported of double parasystole-combined atrial and ventricular parasystole- (author's transl)]. Parasystole is an arrhythmia resulting from simultaneous activity of two independent impulse-forming foci, one of which is protected by the other. Ventricular parasystole which arises from an ectopic focus situated in ventricule is relatively common. On the contrary, supraventricular parasystole which is centered in the atria or atrioventricular junction, is extremely rare. Kaufmann and Rothberger studied first parasystole as an entity, and they reported the first case of atrial parasystole. However, the first correctly mentioned example of atrial parasystole was described by Jervell. In the previous paper, we described one observation on atrial parasystole and discussed on its consisting-mechanism. The occurrence of ventricular parasystole is not a rarity, since it has been estimated to be present once in every 1,200 electrocardiograms taken in a general hospital. In contrast, well-documented cases of atrial parasystole are exceedingly rare, and since the first case of it was reported by Kaufmann and Rothberger, only 25 cases have hitherto been reported. In the present paper is described and discussed a case of the extremely rare combination of atrial and ventricular parasystole with exit block and fusion phenomenon..."} {"id": "PMID:1271579", "title": "[Experimental study on the changes of blood pressure induced by afferent stimulation on the somatic nerves (author's transl)].", "content": "It has been shown by many authors that afferent stimulation of various somatic nerves results in the different types of responses with regard to blood pressure and heart rate. It was revealed by Hunt that afferent \"weak\" stimulation of the somatic nerves caused depressor responses, and \"strong\" stimulation, pressor responses. Ranson and Gordon thought that the depressor response to the afferent stimulation of the somatic nerves would involve the thick myelinated nerve fibers, and the pressor response, the fine non-myelinated nerve fibers. On the other hand, it has been postulated that the socalled chest pain and/or nonspecific complaints observed in patients with myocardial infarction, angina pectoris and neurocirculatory asthenia (NCA) are related to some alterations at the cervical and thoracic vertebral levels of the spinal cord or nerve roots. Maekawa, Hayase and Konishi attached importance to the presence of subclinical arachnoiditis adhesiva cerebrospinalis at the cervical and thoracic vertebral levels in patients of NCA. These facts suggests that the contribution of the spinal cord and the nerve roots to the circularoty system is different between the cervico-thoracic levels and the lumbar levels. Based on these facts, the author stimulated the somatic nerves of both the forelimbs and the hindlimbs afferently in alpha-chloralose anesthetized dogs, with a train of square electric pulses for 20 seconds, and studied the response of the circulatory system to such stimuli.", "contents": "[Experimental study on the changes of blood pressure induced by afferent stimulation on the somatic nerves (author's transl)]. It has been shown by many authors that afferent stimulation of various somatic nerves results in the different types of responses with regard to blood pressure and heart rate. It was revealed by Hunt that afferent \"weak\" stimulation of the somatic nerves caused depressor responses, and \"strong\" stimulation, pressor responses. Ranson and Gordon thought that the depressor response to the afferent stimulation of the somatic nerves would involve the thick myelinated nerve fibers, and the pressor response, the fine non-myelinated nerve fibers. On the other hand, it has been postulated that the socalled chest pain and/or nonspecific complaints observed in patients with myocardial infarction, angina pectoris and neurocirculatory asthenia (NCA) are related to some alterations at the cervical and thoracic vertebral levels of the spinal cord or nerve roots. Maekawa, Hayase and Konishi attached importance to the presence of subclinical arachnoiditis adhesiva cerebrospinalis at the cervical and thoracic vertebral levels in patients of NCA. These facts suggests that the contribution of the spinal cord and the nerve roots to the circularoty system is different between the cervico-thoracic levels and the lumbar levels. Based on these facts, the author stimulated the somatic nerves of both the forelimbs and the hindlimbs afferently in alpha-chloralose anesthetized dogs, with a train of square electric pulses for 20 seconds, and studied the response of the circulatory system to such stimuli."} {"id": "PMID:1271580", "title": "[Gentamicin therapy of infectious diseases by pathogens (author's transl)].", "content": "Gentamicin (GM) was intramuscularly injected to 29 patients with various infections in the doses of 40-60 mg twice a day. The maximum dose was 1,800 mg. Satisfactory clinical results were obtained in the treatment of not only urinary tract infections but also respiratory tract infections, bile duct infections and others. This clinical results would coincide with the fact that almost all organisms isolated had a high sensitivity to GM. No significant abnormal findings was observed in this clinical study. This clinical result indicates that GM is a useful drug in the treatment of various infections.", "contents": "[Gentamicin therapy of infectious diseases by pathogens (author's transl)]. Gentamicin (GM) was intramuscularly injected to 29 patients with various infections in the doses of 40-60 mg twice a day. The maximum dose was 1,800 mg. Satisfactory clinical results were obtained in the treatment of not only urinary tract infections but also respiratory tract infections, bile duct infections and others. This clinical results would coincide with the fact that almost all organisms isolated had a high sensitivity to GM. No significant abnormal findings was observed in this clinical study. This clinical result indicates that GM is a useful drug in the treatment of various infections."} {"id": "PMID:1271581", "title": "[A clinical study on gentamicin in the field of surgery].", "content": "Gentamicin (GM), one of the amino-glucosides, was administered intramuscularly to 27 patients with Pseudomonas and/or other antibiotics resistant infections. The clinical evaluation of the results obtained was classified excellent in 1 case good 6, fair 8, none 11 and indeterminate 1, the effectiveness accounting for 57.7 percent. Satisfactory results were noted in wound infections, peritonitis and urinary tract infections. Among untoward side effects, an elevation in GOT and GPT values was observed in 6 cases, an elevation of BUN value in 1, proteinuria in 1 and hematuria in 1. However, it is difficult to conclude that those side effects were attributable to GM itself because blood transfusion or combined therapy with anti-cancer agents was conducted in these cases during the GM therapy.", "contents": "[A clinical study on gentamicin in the field of surgery]. Gentamicin (GM), one of the amino-glucosides, was administered intramuscularly to 27 patients with Pseudomonas and/or other antibiotics resistant infections. The clinical evaluation of the results obtained was classified excellent in 1 case good 6, fair 8, none 11 and indeterminate 1, the effectiveness accounting for 57.7 percent. Satisfactory results were noted in wound infections, peritonitis and urinary tract infections. Among untoward side effects, an elevation in GOT and GPT values was observed in 6 cases, an elevation of BUN value in 1, proteinuria in 1 and hematuria in 1. However, it is difficult to conclude that those side effects were attributable to GM itself because blood transfusion or combined therapy with anti-cancer agents was conducted in these cases during the GM therapy."} {"id": "PMID:1271582", "title": "[Clinical use of gentamicin in the field of surgery (author's transl)].", "content": "Gentamicin (GM) was intramuscularly administered to 24 patients with various infections (including 1 for prophylaxis of a postoperative infection) in the dose of 40 mg X 2/day for 4-26 days. In children, the maximum daily dose was 3.4 mg/kg and the minimum was 1.2 mg/kg (mean: 2-3 mg/kg). The results obtained are as follows: 1) Clinical efficacy of GM was excellent in 2, good in 9, fair in 4, null in 4 and indeterminate in 5, out of 24 cases. The effective rate was 57.9% (11/19). 2) In 21 strains isolated in 13 cases out of 24, efficacy of GM was good in 10, fair in 5, null in 3 and indeterminate in 3. The effective rate was 55.6% (10/18). 3) No significant side effect was observed in this clinical study.", "contents": "[Clinical use of gentamicin in the field of surgery (author's transl)]. Gentamicin (GM) was intramuscularly administered to 24 patients with various infections (including 1 for prophylaxis of a postoperative infection) in the dose of 40 mg X 2/day for 4-26 days. In children, the maximum daily dose was 3.4 mg/kg and the minimum was 1.2 mg/kg (mean: 2-3 mg/kg). The results obtained are as follows: 1) Clinical efficacy of GM was excellent in 2, good in 9, fair in 4, null in 4 and indeterminate in 5, out of 24 cases. The effective rate was 57.9% (11/19). 2) In 21 strains isolated in 13 cases out of 24, efficacy of GM was good in 10, fair in 5, null in 3 and indeterminate in 3. The effective rate was 55.6% (10/18). 3) No significant side effect was observed in this clinical study."} {"id": "PMID:1271583", "title": "[Clinical experience with gentamicin in complicated urinary tract infections (author's transl)].", "content": "Gentamicin (GM) was intramuscularly administrated to 25 patients with complicated urinary tract infections in doses of 20-120 mg a day for 4-16 days. The results obtained are as follows: 1. The clinical results of GM were excellent in 4, good in 3, fair in 1, poor in 3 and indeterminate in 14 patients out of 25 patients. The effective percentage was 63.6% (7/11). 2. The clinical results of GM against 20 isolates were excellent in 4, good in 3, fair in 1, poor in 3 and indeterminate in 9 isolates. The effective percentage was 63.6% (7/11). 3. In laboratory examinations, BUN elevation was noted in 1 patient, GOT elevation in 2 patients and GPT elevation in 1 patient during GM therapy. No other abnormal findings were observed in this clinical study.", "contents": "[Clinical experience with gentamicin in complicated urinary tract infections (author's transl)]. Gentamicin (GM) was intramuscularly administrated to 25 patients with complicated urinary tract infections in doses of 20-120 mg a day for 4-16 days. The results obtained are as follows: 1. The clinical results of GM were excellent in 4, good in 3, fair in 1, poor in 3 and indeterminate in 14 patients out of 25 patients. The effective percentage was 63.6% (7/11). 2. The clinical results of GM against 20 isolates were excellent in 4, good in 3, fair in 1, poor in 3 and indeterminate in 9 isolates. The effective percentage was 63.6% (7/11). 3. In laboratory examinations, BUN elevation was noted in 1 patient, GOT elevation in 2 patients and GPT elevation in 1 patient during GM therapy. No other abnormal findings were observed in this clinical study."} {"id": "PMID:1271584", "title": "[Clinical experiment of gentamicin in patients with urological diseases (author's transl)].", "content": "1. Gentamicin was effective in 20 patients out of 25 with urological diseases. 2. Gentamicin was more effective on acute symptoms than on chronicones. 3. No marked side effects were noted. 4. No conclusion was drawn on difference in efficacy of gentamicin by dosage, duration of administration and kinds of organisms in this clinical trial.", "contents": "[Clinical experiment of gentamicin in patients with urological diseases (author's transl)]. 1. Gentamicin was effective in 20 patients out of 25 with urological diseases. 2. Gentamicin was more effective on acute symptoms than on chronicones. 3. No marked side effects were noted. 4. No conclusion was drawn on difference in efficacy of gentamicin by dosage, duration of administration and kinds of organisms in this clinical trial."} {"id": "PMID:1271585", "title": "[Clinical studies on gentamicin in complicated urinary tract infections (author's transl)].", "content": "Twenty cases with complicated urinary tract infections were treated with gentamicin. Good results were obtained in 7 of 14 cases with chronic pyelonephritis and 2 of 4 cases with chronic cystitis and in 1 of 2 cases with acute prostatitis. No side effect was observed throughout this treatment. But in laboratory examination, slight elevation of S-GOT and S-GPT was observed in 3 of 20 cases after gentamicin treatment.", "contents": "[Clinical studies on gentamicin in complicated urinary tract infections (author's transl)]. Twenty cases with complicated urinary tract infections were treated with gentamicin. Good results were obtained in 7 of 14 cases with chronic pyelonephritis and 2 of 4 cases with chronic cystitis and in 1 of 2 cases with acute prostatitis. No side effect was observed throughout this treatment. But in laboratory examination, slight elevation of S-GOT and S-GPT was observed in 3 of 20 cases after gentamicin treatment."} {"id": "PMID:1271586", "title": "[Antibacterial and bactericidal activity of tinidazole against anaerobic bacteria comparing with metronidazole (author's transl)].", "content": "Antibacterial activity of tinidazole (1-2-(ethylsulfonyl)-2-methyl-5-nitroimidazole) against anaerobic bacteria including Peptococcus, Peptostreptococcus, Eubacterium, Propionibacterium, Bacteroides and Fusobacterium was studied by agar dilution method comparing with metronidazole. In addition to this work, bactericidal effect of tinidazole and metronidazole against P. prevotii, B. fragilis ss. fragilis and F. varium was examined by quantitative culture method after incubation in GAM broth containing of 4 MIC, 2 MIC, 1 MIC and 1/2 MIC of both drugs against each of three strains for 1, 3, 6, 12 and 24 hours. All the strains of Peptococcus and Peptostreptococcus including P. anaerobius, P. saccharolyticus, P. prevotii and Ps. anaerobius and others were susceptible to a concentration of 6.25 mcg/ml of this drug. A concentration of 3.13 mcg/ml inhibited all strains of Bacteroides including B. fragilis ss. fragilis (12 strains), ss. vulgatus (5 strains), ss. thetaiotaomicron (4 strains) and ss. distasonis (2 strains). To this concentration all strains of Fusobacterium including F. varium (20 strains), F. mortiferum (2 strains) and other Fusobacterium sp. (5 strains) were susceptible. On the contrary, Propionibacterium acnes (6 strains) was resistant to 100 mcg/ml or more of tinidazole and metronidazole. The antibacterial activity of tinidazole was stronger against Bacteroides than that of metronidazole, while almost equal against Peptococcus, Peptostreptococcus, Eubacterium and Fusobacterium. Tinidazole was bactericidal against F. varium in a concentration of 2 MIC till 24 hours of incubation but did not show such an activity on B. fragilis ss. fragilis in same concentration even after 12 hours of incubation. On the other hand, metronidazole was bactericidal against B. fragilis ss. fragilis while was not against F. varium. Against P. prevotii bactericidal activity of both drugs was similar. Tinidazole as well as metronidazole is an excellent chemotherapeutic agent against anaerobic bacteria excluding Propionibacterium acnes and Bifidobacterium adolescentis.", "contents": "[Antibacterial and bactericidal activity of tinidazole against anaerobic bacteria comparing with metronidazole (author's transl)]. Antibacterial activity of tinidazole (1-2-(ethylsulfonyl)-2-methyl-5-nitroimidazole) against anaerobic bacteria including Peptococcus, Peptostreptococcus, Eubacterium, Propionibacterium, Bacteroides and Fusobacterium was studied by agar dilution method comparing with metronidazole. In addition to this work, bactericidal effect of tinidazole and metronidazole against P. prevotii, B. fragilis ss. fragilis and F. varium was examined by quantitative culture method after incubation in GAM broth containing of 4 MIC, 2 MIC, 1 MIC and 1/2 MIC of both drugs against each of three strains for 1, 3, 6, 12 and 24 hours. All the strains of Peptococcus and Peptostreptococcus including P. anaerobius, P. saccharolyticus, P. prevotii and Ps. anaerobius and others were susceptible to a concentration of 6.25 mcg/ml of this drug. A concentration of 3.13 mcg/ml inhibited all strains of Bacteroides including B. fragilis ss. fragilis (12 strains), ss. vulgatus (5 strains), ss. thetaiotaomicron (4 strains) and ss. distasonis (2 strains). To this concentration all strains of Fusobacterium including F. varium (20 strains), F. mortiferum (2 strains) and other Fusobacterium sp. (5 strains) were susceptible. On the contrary, Propionibacterium acnes (6 strains) was resistant to 100 mcg/ml or more of tinidazole and metronidazole. The antibacterial activity of tinidazole was stronger against Bacteroides than that of metronidazole, while almost equal against Peptococcus, Peptostreptococcus, Eubacterium and Fusobacterium. Tinidazole was bactericidal against F. varium in a concentration of 2 MIC till 24 hours of incubation but did not show such an activity on B. fragilis ss. fragilis in same concentration even after 12 hours of incubation. On the other hand, metronidazole was bactericidal against B. fragilis ss. fragilis while was not against F. varium. Against P. prevotii bactericidal activity of both drugs was similar. Tinidazole as well as metronidazole is an excellent chemotherapeutic agent against anaerobic bacteria excluding Propionibacterium acnes and Bifidobacterium adolescentis."} {"id": "PMID:1271587", "title": "[Clinical trials with amoxicillin (Pasetocin 'Kyowa') on infections of respiratory apparatus (author's transl)].", "content": "Amoxicillin at a daily dose of 1-1.5 g was orally administered to total 30 cases comprising 6 of acute tonsillitis, 6 of chronic tonsillitis, 8 of acute bronchitis, 4 of chronic bronchitis, 4 of bronchiectasis, 1 of suppurative diseases of the lung and 1 of exudative pleurisy. The clinical results and side effects are reported. 1. The effect of amoxicillin was remarkably good in 15 of 30 cases with infections of respiratory apparatus (50%), good in 7(23%), poor in 5(17%) and unknown in 3(10%); the effectiveness was 73%. 2. In terms of diseases, amoxicillin was effective in 33% of acute tonsillitis, in 50% of chronic tonsillitis and in all of acute bronchitis, chronic bronchitis, bronchiectasia and suppurative disease of the lung. No effect was observed in exudative pleurisy. 3. In terms of strains detected, amoxicillin was effective in 67% of Staphylococcus aureus, in 89% of Haemophilus and in 50% of Klebsiella. This drug was effective in all cases caused by Escherichia coli, Acinetobacter calcoacetines, beta-Streptococcus, Flavobacterium, Streptococcus pneumonia, though these strains were not frequently detected. Pseudomonas aeruginosa had no response to this drug. 4. Two cases of transient hepatic dysfunction, 6 of eruption, 5 of gastro-intestinal disorders, 1 of arthralgia and 1 of pyrexia were observed as side effects (some cases had side effects in overlap).", "contents": "[Clinical trials with amoxicillin (Pasetocin 'Kyowa') on infections of respiratory apparatus (author's transl)]. Amoxicillin at a daily dose of 1-1.5 g was orally administered to total 30 cases comprising 6 of acute tonsillitis, 6 of chronic tonsillitis, 8 of acute bronchitis, 4 of chronic bronchitis, 4 of bronchiectasis, 1 of suppurative diseases of the lung and 1 of exudative pleurisy. The clinical results and side effects are reported. 1. The effect of amoxicillin was remarkably good in 15 of 30 cases with infections of respiratory apparatus (50%), good in 7(23%), poor in 5(17%) and unknown in 3(10%); the effectiveness was 73%. 2. In terms of diseases, amoxicillin was effective in 33% of acute tonsillitis, in 50% of chronic tonsillitis and in all of acute bronchitis, chronic bronchitis, bronchiectasia and suppurative disease of the lung. No effect was observed in exudative pleurisy. 3. In terms of strains detected, amoxicillin was effective in 67% of Staphylococcus aureus, in 89% of Haemophilus and in 50% of Klebsiella. This drug was effective in all cases caused by Escherichia coli, Acinetobacter calcoacetines, beta-Streptococcus, Flavobacterium, Streptococcus pneumonia, though these strains were not frequently detected. Pseudomonas aeruginosa had no response to this drug. 4. Two cases of transient hepatic dysfunction, 6 of eruption, 5 of gastro-intestinal disorders, 1 of arthralgia and 1 of pyrexia were observed as side effects (some cases had side effects in overlap)."} {"id": "PMID:1271588", "title": "Anaerobic coryneforms isolated from human bone marrow and skin. Chemical, biochemical and serological studies and some of their biological activities.", "content": "Eighteen isolates if anaerobic coryneforms from human bone marrow and skin and four type strains of Propionibacterium were studied chemically, biochemically and antigenically. All of the isolates were identified as Propionibacterium acnes; of the 18 isolates,16 belonged to sterotype I and two to serotype II. By means of gas liquid chromatography and mass spectral analysis, a large amount of iso-type fatty acids, such as iso-pentadecanoic and iso-heptadecanoic acids were detected in whole cells of isolates and type strains. Antitumor and adjuvant effects of the isolates and type strains were found to differ considerably among the strains. One of the isolates, P. acnes C-7, which showed potent biological activities was fractionated by hot phenol-water extraction. The resulting insoluble middle layer was found the most effective in tumor protection, adjuvant action in immune response and phagocytic activity in mice.", "contents": "Anaerobic coryneforms isolated from human bone marrow and skin. Chemical, biochemical and serological studies and some of their biological activities. Eighteen isolates if anaerobic coryneforms from human bone marrow and skin and four type strains of Propionibacterium were studied chemically, biochemically and antigenically. All of the isolates were identified as Propionibacterium acnes; of the 18 isolates,16 belonged to sterotype I and two to serotype II. By means of gas liquid chromatography and mass spectral analysis, a large amount of iso-type fatty acids, such as iso-pentadecanoic and iso-heptadecanoic acids were detected in whole cells of isolates and type strains. Antitumor and adjuvant effects of the isolates and type strains were found to differ considerably among the strains. One of the isolates, P. acnes C-7, which showed potent biological activities was fractionated by hot phenol-water extraction. The resulting insoluble middle layer was found the most effective in tumor protection, adjuvant action in immune response and phagocytic activity in mice."} {"id": "PMID:1271590", "title": "Electrocardiographic changes in traumatized patients.", "content": "Traumatized patients who sustain a severe physical or psychological insult may develop myocardial ischemic changes, espicially those patients over the age of 40 years. The electrocardiogram (EKG) findings in 34 chest injury patients out of 200 multiple injury cases over a period of two years were studied. Two types of myocardial changes were found: injury pattern (of a permanent character) and ischemic pattern (of a transient nature). The first type was more frequent in the penetrating noncardiac chest injury cases, and the second more common in the blunt chest injury cases. It is necessary to make early and serial EKG tracings on traumatized patients in order to detect myocardial changes.", "contents": "Electrocardiographic changes in traumatized patients. Traumatized patients who sustain a severe physical or psychological insult may develop myocardial ischemic changes, espicially those patients over the age of 40 years. The electrocardiogram (EKG) findings in 34 chest injury patients out of 200 multiple injury cases over a period of two years were studied. Two types of myocardial changes were found: injury pattern (of a permanent character) and ischemic pattern (of a transient nature). The first type was more frequent in the penetrating noncardiac chest injury cases, and the second more common in the blunt chest injury cases. It is necessary to make early and serial EKG tracings on traumatized patients in order to detect myocardial changes."} {"id": "PMID:1271593", "title": "Fluid and electrolyte problems in the emergency department.", "content": "In management of fluid and electrolyte problems in the emergency department several important principles are: (1) never completely trust the laboratory, (2) abnormalities should be treated at approximately the rate at which they developed, (3) correct only half the calculated deficit at a time and reevaluate the patient, (4) the highest priority in treatment is maintenance of intravascular volume and tissue perfusion. The osmolarity of fluid compartments as related to the fluid and electrolyte responses to stress and resultant fluid requirements for basic needs, current losses and deficits of fluid and electrolytes are discussed in depth. The characteristics of volume, sodium, potassium, chloride, bicarbonate, calcium and magnesium deficits and how to correct them are outlined.", "contents": "Fluid and electrolyte problems in the emergency department. In management of fluid and electrolyte problems in the emergency department several important principles are: (1) never completely trust the laboratory, (2) abnormalities should be treated at approximately the rate at which they developed, (3) correct only half the calculated deficit at a time and reevaluate the patient, (4) the highest priority in treatment is maintenance of intravascular volume and tissue perfusion. The osmolarity of fluid compartments as related to the fluid and electrolyte responses to stress and resultant fluid requirements for basic needs, current losses and deficits of fluid and electrolytes are discussed in depth. The characteristics of volume, sodium, potassium, chloride, bicarbonate, calcium and magnesium deficits and how to correct them are outlined."} {"id": "PMID:1271594", "title": "Simple febrile convulsions.", "content": "Simple febrile convulsions occur in otherwise normal children, aged six months to five years, with extracranial infection. Cerebrospinal fluid examination should be done on all children with their first febrile convulsion to rule out an underlying organic disease, especially purulent meningitis. Initial treatment includes antipyretics, tepid sponging and intramuscular phenobarbital. If a seizure recurs, the usual anticonvulsant measures should be carried out and, if prolonged, the patient should receive appropriated doses of diazepam or phenobarbital, intravenously. Patients with suspected epileptic convulsive disorders precipitated by fever, or those with seizures thought to be associated with underlying organic disease, should be hospitalized for further evaluation or treatment or both. Patients with simple febrile convulsions have a benign disorder and can be safely treated as outpatients.", "contents": "Simple febrile convulsions. Simple febrile convulsions occur in otherwise normal children, aged six months to five years, with extracranial infection. Cerebrospinal fluid examination should be done on all children with their first febrile convulsion to rule out an underlying organic disease, especially purulent meningitis. Initial treatment includes antipyretics, tepid sponging and intramuscular phenobarbital. If a seizure recurs, the usual anticonvulsant measures should be carried out and, if prolonged, the patient should receive appropriated doses of diazepam or phenobarbital, intravenously. Patients with suspected epileptic convulsive disorders precipitated by fever, or those with seizures thought to be associated with underlying organic disease, should be hospitalized for further evaluation or treatment or both. Patients with simple febrile convulsions have a benign disorder and can be safely treated as outpatients."} {"id": "PMID:1271595", "title": "Life-support system: emergency medical care for conventions.", "content": "The life-support system described provides on-site emergency medical care for a designated group of people. It consists of a fixed subunit, a back-up emergency department; a temporary subunit, a life support station, and a mobile subunit, an ambulance and mobile medical personnel. A proposal for a life-support system for indoor conventions is presented with specifications of personnel, communications, supplies, registrant education and life-support team function. Results, critique, and discussion of a life-support station at the 1974 Annual ACEP/EDNA Scientific Assembly are presented.", "contents": "Life-support system: emergency medical care for conventions. The life-support system described provides on-site emergency medical care for a designated group of people. It consists of a fixed subunit, a back-up emergency department; a temporary subunit, a life support station, and a mobile subunit, an ambulance and mobile medical personnel. A proposal for a life-support system for indoor conventions is presented with specifications of personnel, communications, supplies, registrant education and life-support team function. Results, critique, and discussion of a life-support station at the 1974 Annual ACEP/EDNA Scientific Assembly are presented."} {"id": "PMID:1271596", "title": "Air embolism and decompression sickness in scuba divers.", "content": "The recognition and prompt treatment of air embolism and decompression sickness by the emergency physician can do much to reverse the unfavorable outcome of these two medical emergencies. Recognition depends on the physician maintaining a high index of suspicion. While the primary treatment for these disorders is recompression, other forms of therapy are outlined which must be instituted promptly.", "contents": "Air embolism and decompression sickness in scuba divers. The recognition and prompt treatment of air embolism and decompression sickness by the emergency physician can do much to reverse the unfavorable outcome of these two medical emergencies. Recognition depends on the physician maintaining a high index of suspicion. While the primary treatment for these disorders is recompression, other forms of therapy are outlined which must be instituted promptly."} {"id": "PMID:1271597", "title": "The embedded broken-off needle.", "content": "A technique for removal of broken-off needles embedded in the sole of the foot is described. Posteroanterior and lateral x-ray films with a radiopaque marker at the needle entry point make it possible to calculate the position of the needle. Using the marker as a third point of reference, solid geometry is used to identify the position and angle of the needle in the space of the foot. A stab wound using a No. 11 blade is aimed on a 90 degree angle at the middle of the needle, permitting its easy removal.", "contents": "The embedded broken-off needle. A technique for removal of broken-off needles embedded in the sole of the foot is described. Posteroanterior and lateral x-ray films with a radiopaque marker at the needle entry point make it possible to calculate the position of the needle. Using the marker as a third point of reference, solid geometry is used to identify the position and angle of the needle in the space of the foot. A stab wound using a No. 11 blade is aimed on a 90 degree angle at the middle of the needle, permitting its easy removal."} {"id": "PMID:1271602", "title": "Progressive quadriparesis, mental retardation, retinitis pigmentosa, and hearing loss: report of two sibs.", "content": "Three- and four-year-old brothers, ostensibly with a nonprogressive spastic quadriparesis, had retinitis pigmentosa and mental retardation. One had clinical deafness. The brothers showed little developmental progress in infancy and exhibited deterioration in childhood. Known metabolic and acquired causes were excluded. Although they have some features of several other syndromes,the condition reported here is unique.", "contents": "Progressive quadriparesis, mental retardation, retinitis pigmentosa, and hearing loss: report of two sibs. Three- and four-year-old brothers, ostensibly with a nonprogressive spastic quadriparesis, had retinitis pigmentosa and mental retardation. One had clinical deafness. The brothers showed little developmental progress in infancy and exhibited deterioration in childhood. Known metabolic and acquired causes were excluded. Although they have some features of several other syndromes,the condition reported here is unique."} {"id": "PMID:1271610", "title": "[Valvulo-muscular kinetics of the heart in some rhythm and conductivity disorders].", "content": "To study the valvulo-muscular kinetics of the heart in the presence of various rhythm and conductivity disorders 20 patients were examined by means of ultrasonic valvulocardiography, electrokimography, oesophagoatriography and rheography. It was found that in cases of left venous ostium stenosis complicated by atrial fibrillation the opening of the mitral valve during the diastole occurs in 0.03--0.04 sec following the beginning of the II sound, and in cases of cardiosclerosis complicated by atrial fibrillation -- in 0.08 sec following the beginning of the II sound of the phonocardiogram. In cases of atrioventricular block, stage I and II, a lagging of the perisystolic signal was noted on the ultrasonic cardiogram after the termination of the P--wave of ECG by 0.02--0.08 sec, with the period of the perisystolic signal growing up to 0.01 sec. In cases of an incomplete atrioventicular block, stage III, the perisystolic signal during the blocked perisystole was found to last as long as 0.18 sec. In cases of complete atrioventricular block the perisystolic signal was found to lagg behind after the termination of the P--wave on ECG by 0.06--0.08 sec. In cases of ventricular extrasystole early movements of the mitral valve were noted, preceeding the extrasystolic complex on ECG by 0.08 sec.", "contents": "[Valvulo-muscular kinetics of the heart in some rhythm and conductivity disorders]. To study the valvulo-muscular kinetics of the heart in the presence of various rhythm and conductivity disorders 20 patients were examined by means of ultrasonic valvulocardiography, electrokimography, oesophagoatriography and rheography. It was found that in cases of left venous ostium stenosis complicated by atrial fibrillation the opening of the mitral valve during the diastole occurs in 0.03--0.04 sec following the beginning of the II sound, and in cases of cardiosclerosis complicated by atrial fibrillation -- in 0.08 sec following the beginning of the II sound of the phonocardiogram. In cases of atrioventricular block, stage I and II, a lagging of the perisystolic signal was noted on the ultrasonic cardiogram after the termination of the P--wave of ECG by 0.02--0.08 sec, with the period of the perisystolic signal growing up to 0.01 sec. In cases of an incomplete atrioventicular block, stage III, the perisystolic signal during the blocked perisystole was found to last as long as 0.18 sec. In cases of complete atrioventricular block the perisystolic signal was found to lagg behind after the termination of the P--wave on ECG by 0.06--0.08 sec. In cases of ventricular extrasystole early movements of the mitral valve were noted, preceeding the extrasystolic complex on ECG by 0.08 sec."} {"id": "PMID:1271611", "title": "[Morphology of the lungs during various periods of artificial ventilation after surgical correction of heart disease].", "content": "The lungs of 84 patients dying following radical corrections of their congenital or acquired heart diseases were examined. The dynamics of the morphological changes developing in the pulmonary tissue depending on the duration of artificial pulmonary ventilation in the postoperative period is described. The pathogenesis of pulmonary complications of long-term artificial ventilation of the lungs is suggested.", "contents": "[Morphology of the lungs during various periods of artificial ventilation after surgical correction of heart disease]. The lungs of 84 patients dying following radical corrections of their congenital or acquired heart diseases were examined. The dynamics of the morphological changes developing in the pulmonary tissue depending on the duration of artificial pulmonary ventilation in the postoperative period is described. The pathogenesis of pulmonary complications of long-term artificial ventilation of the lungs is suggested."} {"id": "PMID:1271612", "title": "[Rheopulmonographic and pathomorphological parallels in congenital heart defects with increased blood circulation in the lungs].", "content": "A comparison of clinico-pulmonographic and morphological changes in the lesser circulation of 12 persons who died due to congenital heart failures involving an increased blood flow in the lungs revealed the presence of a correlation between these changes in the phases of compensation and decompensation.", "contents": "[Rheopulmonographic and pathomorphological parallels in congenital heart defects with increased blood circulation in the lungs]. A comparison of clinico-pulmonographic and morphological changes in the lesser circulation of 12 persons who died due to congenital heart failures involving an increased blood flow in the lungs revealed the presence of a correlation between these changes in the phases of compensation and decompensation."} {"id": "PMID:1271613", "title": "[Heart preservation by means of hypothermia and hyperbaric oxygenation].", "content": "The efficiency of the methods of hypothermia and hyperbaric oxygenation for the preservation of canine hearts was studied. The cardiac function was found to reestablish itself nearly completely after 3 hours of preservation, despite some significant metabolic shifts -- disintegration of oxidation and phosphorylation, activation of lysosomal enzymes, reduction of the store of adenyl macroergs and biogenic amines. Five hours of preservation result in irreversible changes in the heart.", "contents": "[Heart preservation by means of hypothermia and hyperbaric oxygenation]. The efficiency of the methods of hypothermia and hyperbaric oxygenation for the preservation of canine hearts was studied. The cardiac function was found to reestablish itself nearly completely after 3 hours of preservation, despite some significant metabolic shifts -- disintegration of oxidation and phosphorylation, activation of lysosomal enzymes, reduction of the store of adenyl macroergs and biogenic amines. Five hours of preservation result in irreversible changes in the heart."} {"id": "PMID:1271617", "title": "[Registration of cases of non-hospitalized patients sudden death due to acute myocardial infarct and acute coronary insufficiency and its importance for further improvement in the control of ischemic heart disease].", "content": "An analysis is presented on the recording, in accordance with the WHO programme, of extramural deaths in the city of Kaunas attributable to acute myocardial infarction and acute coronary insufficiency. In 89 patients who died outside of hospital walls the morphological studies revealed only a scar (not exceeding 0.5 cm in size) of a sustained acute myocardial infarction. In 64% of them the diagnosis of acute myocardial infarction was not made intravitally. The recording of cases of extrahospital mortality is of great practical importance. It indicates that the medical aid to patients with ischaemic heart disease remains insufficient.", "contents": "[Registration of cases of non-hospitalized patients sudden death due to acute myocardial infarct and acute coronary insufficiency and its importance for further improvement in the control of ischemic heart disease]. An analysis is presented on the recording, in accordance with the WHO programme, of extramural deaths in the city of Kaunas attributable to acute myocardial infarction and acute coronary insufficiency. In 89 patients who died outside of hospital walls the morphological studies revealed only a scar (not exceeding 0.5 cm in size) of a sustained acute myocardial infarction. In 64% of them the diagnosis of acute myocardial infarction was not made intravitally. The recording of cases of extrahospital mortality is of great practical importance. It indicates that the medical aid to patients with ischaemic heart disease remains insufficient."} {"id": "PMID:1271618", "title": "[Sudden death due to acute coronary insufficiency].", "content": "The study was conducted in the course of 2 years in accordance with the programme of myocardial infarction register of all mortality cases among the inhabitants of one of the Moscow districts. In conformity with the criteria recommended by the WHO Expert Committee, general figures of sudden death incidence at the age of 20 to 64 years comprised 80.3--76.2 and 32.7--34.5 per 100,000 males and females, respectively, during the 1st and 2nd year of observation. Autopsies performed in 89.5% of the mortality cases established that only in 39.8% of the cases death ensued in the presence of fresh foci of necrosis in the myocardium, while in the rest no myocardial infarction was found. In an overwhelming majority of the dying patients severe stenoses or occlusions of the coronary arteries were seen, and only 13% had no stenoses. However, the latter group showed fresh necroses or postinfarction cicatrices in the myocardium. The obtained data indicate that sudden death occupies an important place in the structure of mortality in ischaemic heart disease. It has been demonstrated that no reduction of general mortality due to myocardial infarction is possible without effective measures against this kind of death.", "contents": "[Sudden death due to acute coronary insufficiency]. The study was conducted in the course of 2 years in accordance with the programme of myocardial infarction register of all mortality cases among the inhabitants of one of the Moscow districts. In conformity with the criteria recommended by the WHO Expert Committee, general figures of sudden death incidence at the age of 20 to 64 years comprised 80.3--76.2 and 32.7--34.5 per 100,000 males and females, respectively, during the 1st and 2nd year of observation. Autopsies performed in 89.5% of the mortality cases established that only in 39.8% of the cases death ensued in the presence of fresh foci of necrosis in the myocardium, while in the rest no myocardial infarction was found. In an overwhelming majority of the dying patients severe stenoses or occlusions of the coronary arteries were seen, and only 13% had no stenoses. However, the latter group showed fresh necroses or postinfarction cicatrices in the myocardium. The obtained data indicate that sudden death occupies an important place in the structure of mortality in ischaemic heart disease. It has been demonstrated that no reduction of general mortality due to myocardial infarction is possible without effective measures against this kind of death."} {"id": "PMID:1271619", "title": "[Catecholamines and other vasoactive substances in blood in cardiogenic shock].", "content": "The blood levels of catecholamines, serotonin, histamine and acetylcholine were studied in 17 patients with severe and moderate coronary shock. The blood level of the above vasoactive substances varied widely, and no clear regularity was noted in the changes of the content of the catecholamines, histamine, serotonin and acetylcholine. A relatively higher (on the average) level of noradrenaline was noted in severe shock, in contrast to the moderate cases, as well as a relatively low level of noradrenaline and acetylcholine in the blood of patients with a full atrioventricular block and bradycardia. In studying the vasoactive substances dynamically similar, phase-like fluctuations of the blood level of histamine and serotonin were noted in some patients. In a few cases similar, often phase-like, changes were also noted in the blood content of noradrenaline and acetylcholine", "contents": "[Catecholamines and other vasoactive substances in blood in cardiogenic shock]. The blood levels of catecholamines, serotonin, histamine and acetylcholine were studied in 17 patients with severe and moderate coronary shock. The blood level of the above vasoactive substances varied widely, and no clear regularity was noted in the changes of the content of the catecholamines, histamine, serotonin and acetylcholine. A relatively higher (on the average) level of noradrenaline was noted in severe shock, in contrast to the moderate cases, as well as a relatively low level of noradrenaline and acetylcholine in the blood of patients with a full atrioventricular block and bradycardia. In studying the vasoactive substances dynamically similar, phase-like fluctuations of the blood level of histamine and serotonin were noted in some patients. In a few cases similar, often phase-like, changes were also noted in the blood content of noradrenaline and acetylcholine"} {"id": "PMID:1271620", "title": "[Prevention of ventricular fibrillation during the acute phase of experimentally induced myocardial infarction by affecting the ion and acid-base balance of the heart].", "content": "For the purpose of prevention of ventricular fibrillation in acute coronary insufficiency a multi-component solution was developed that produces a normalizing effect on the acid-base and ion balance disorders in the heart under ischaemia. The injection of this solution into the left atrium sharply elevated the ventricular fibrillation threshold in cats with an occluded coronary artery. The administration of the solution into the left atrium of dogs following an occlusion of the descending left coronary artery prevented the development of fibrillation in all the experiments, while in the control series of experiments it developed in 62% of cases (p less than 0.001). The solution was decided to posses a high antifibrillation activity that manifests itself when the solution is introduced into the left atrium, and the mechanisms of the beneficial effects of the solution are discussed", "contents": "[Prevention of ventricular fibrillation during the acute phase of experimentally induced myocardial infarction by affecting the ion and acid-base balance of the heart]. For the purpose of prevention of ventricular fibrillation in acute coronary insufficiency a multi-component solution was developed that produces a normalizing effect on the acid-base and ion balance disorders in the heart under ischaemia. The injection of this solution into the left atrium sharply elevated the ventricular fibrillation threshold in cats with an occluded coronary artery. The administration of the solution into the left atrium of dogs following an occlusion of the descending left coronary artery prevented the development of fibrillation in all the experiments, while in the control series of experiments it developed in 62% of cases (p less than 0.001). The solution was decided to posses a high antifibrillation activity that manifests itself when the solution is introduced into the left atrium, and the mechanisms of the beneficial effects of the solution are discussed"} {"id": "PMID:1271621", "title": "[Drug prevention of cardiac rhythm disorders during the acute period of myocardial infarct].", "content": "Among 152 patients with myocardial infarction admitted to a specialized department within a few hours (1st day) of the onset of the disease without cardiac rhythm disorders, or with \"minor\" arrhythmias, 31 patients were receiving Panangine intravenously, 10--20 ml daily, for 7 days since the moment of admission. Another group of patients was comprised of 75 persons who, in addition to the above regimen of Panangine therapy, received at the moment of their admission a single intramuscular injection of Retabolil (50 mg). The control group was formed by 46 patients receiving no antiarrhythmic drugs. Monitoring of the cardiac rhythm during the acute period of myocardial infarction demonstrated that with preventive employment of Panangine prognostically dangerous rhythm disorders (especially paroxysmal tachycardia) developed less often than in the controls. A combined employment of Panangine and Retabolil resulted in a still better preventive effect, largely preventing, among other developments, the appearance of multiple polytopic extrasystoles. No ventricular fibrillation was observed in the examined patients.", "contents": "[Drug prevention of cardiac rhythm disorders during the acute period of myocardial infarct]. Among 152 patients with myocardial infarction admitted to a specialized department within a few hours (1st day) of the onset of the disease without cardiac rhythm disorders, or with \"minor\" arrhythmias, 31 patients were receiving Panangine intravenously, 10--20 ml daily, for 7 days since the moment of admission. Another group of patients was comprised of 75 persons who, in addition to the above regimen of Panangine therapy, received at the moment of their admission a single intramuscular injection of Retabolil (50 mg). The control group was formed by 46 patients receiving no antiarrhythmic drugs. Monitoring of the cardiac rhythm during the acute period of myocardial infarction demonstrated that with preventive employment of Panangine prognostically dangerous rhythm disorders (especially paroxysmal tachycardia) developed less often than in the controls. A combined employment of Panangine and Retabolil resulted in a still better preventive effect, largely preventing, among other developments, the appearance of multiple polytopic extrasystoles. No ventricular fibrillation was observed in the examined patients."} {"id": "PMID:1271623", "title": "[Influence of anti-arrhythmia agents on electrolyte metabolism].", "content": "In 73 patients with hypertensive and ischemic heart diseases the total body potassium content was studied by measuring natural radioactivity with reference to K40 before and after administration of quinidine, isoptin and inderal. Furthermore, in 74 patients subject to determination was the blood plasma and erythrocytes potassium and sodium levels on application of the said agents. Following administration of quinidine and isoptin the level of total potassium in the organism was rising substantially, while taking inderal lead to a drop of the potassium concentration in the body. No clear cut parallels between the blood plasma and erythrocytes ontent and the level of total potassium in the organism could be uncovered. Mechanisms underlying the antiarrhythmic action of quinidine, isoptin and inderal are discussed.", "contents": "[Influence of anti-arrhythmia agents on electrolyte metabolism]. In 73 patients with hypertensive and ischemic heart diseases the total body potassium content was studied by measuring natural radioactivity with reference to K40 before and after administration of quinidine, isoptin and inderal. Furthermore, in 74 patients subject to determination was the blood plasma and erythrocytes potassium and sodium levels on application of the said agents. Following administration of quinidine and isoptin the level of total potassium in the organism was rising substantially, while taking inderal lead to a drop of the potassium concentration in the body. No clear cut parallels between the blood plasma and erythrocytes ontent and the level of total potassium in the organism could be uncovered. Mechanisms underlying the antiarrhythmic action of quinidine, isoptin and inderal are discussed."} {"id": "PMID:1271624", "title": "[Changes in cerebral circulation during various types of cardiac arrhythmias].", "content": "The cerebral volume blood flow was measured in acute canine experiments in three major arteries of the brain using an electromagnetic flowmeter. Paroxysms of ventricular tachycardia caused by electric stimulation of the heart resulted in varying degrees of reduction of the cerebral blood flow and arterial pressure that was most significant with cardiac contractions rate exceeding 240/min. Bradycardia with the contractions rate below 60/min also caused a reduction of the cerebral blood flow and arterial pressure. A parabolic correlation was revealed between the changes in the heart contractions rate and the amount of decrease of the cerebral blood flow and arterial pressure. Grouped ventricular extrasystoles resulted in a brief sharp fall of the cerebral blood flow...", "contents": "[Changes in cerebral circulation during various types of cardiac arrhythmias]. The cerebral volume blood flow was measured in acute canine experiments in three major arteries of the brain using an electromagnetic flowmeter. Paroxysms of ventricular tachycardia caused by electric stimulation of the heart resulted in varying degrees of reduction of the cerebral blood flow and arterial pressure that was most significant with cardiac contractions rate exceeding 240/min. Bradycardia with the contractions rate below 60/min also caused a reduction of the cerebral blood flow and arterial pressure. A parabolic correlation was revealed between the changes in the heart contractions rate and the amount of decrease of the cerebral blood flow and arterial pressure. Grouped ventricular extrasystoles resulted in a brief sharp fall of the cerebral blood flow..."} {"id": "PMID:1271625", "title": "[Electocardiographic changes in cerebral stroke patients with atherosclerosis and hypertension].", "content": "A dynamic electrocardiographic observation was conducted in 200 patients with cerebral stroke (57 patients had intracerebral haemorrhages, 143--ischaemic strokes). ECG changes as a sequele of cerebral stroke were found to manifest themselves in various cardiac rhythm disorders, disturbances in the conductivity and repolarization phase. \"Cerebrogenic\" ECG changes were found in 76.5% of the patients. ECG changes were noted to occur in different combinations which permits to distinguish three main variants.", "contents": "[Electocardiographic changes in cerebral stroke patients with atherosclerosis and hypertension]. A dynamic electrocardiographic observation was conducted in 200 patients with cerebral stroke (57 patients had intracerebral haemorrhages, 143--ischaemic strokes). ECG changes as a sequele of cerebral stroke were found to manifest themselves in various cardiac rhythm disorders, disturbances in the conductivity and repolarization phase. \"Cerebrogenic\" ECG changes were found in 76.5% of the patients. ECG changes were noted to occur in different combinations which permits to distinguish three main variants."} {"id": "PMID:1271626", "title": "[Atrial dissociation].", "content": "A case of atrial dissociation with left-side atrial flutter is described in a patient with a transmural anterior myocardial infarction. A favourable outcome of this arrhythmia was achieved. Inviting the literature data the paper discusses the problems of impulse transmission from the right atrium to the left, the mechanism and causes of atrial dissociation, the electrocardiographic and differential diagnosis of this arrythmia, the prognosis in atrial dissociation.", "contents": "[Atrial dissociation]. A case of atrial dissociation with left-side atrial flutter is described in a patient with a transmural anterior myocardial infarction. A favourable outcome of this arrhythmia was achieved. Inviting the literature data the paper discusses the problems of impulse transmission from the right atrium to the left, the mechanism and causes of atrial dissociation, the electrocardiographic and differential diagnosis of this arrythmia, the prognosis in atrial dissociation."} {"id": "PMID:1271627", "title": "[Micro-focal myocardial infarct with a relapsing course].", "content": "The observation was conducted in 96 patients with micro-focal myocardial infarction who developed recurrences within the acute or subacute period (up to 2 months). In 47 patients the secondary infarction was of a micro-focal nature, in 49 -- macro-focal. Recurrence of micro-focal infarctions was observed predominantly in aged patients with a long history of angina pectoris who have had repeated myocardial infarctions earlier. Recurrent macro-focal myocardial infarctions were more often noted in younger patients with a brief coronary history, their primary infarction having been of a micro-focal nature. In both groups of patients congestive cardiac insufficiency and pulmonary oedema were often noted. Cardiogenic shock was mainly seen in those with relapses of macro-focal myocardial infarction. Recurrent microfocal myocardial infarction was often characterized by the development of rhythm and conductivity disorders and high mortality rate, especially when the recurrence was of a macro-focal type.", "contents": "[Micro-focal myocardial infarct with a relapsing course]. The observation was conducted in 96 patients with micro-focal myocardial infarction who developed recurrences within the acute or subacute period (up to 2 months). In 47 patients the secondary infarction was of a micro-focal nature, in 49 -- macro-focal. Recurrence of micro-focal infarctions was observed predominantly in aged patients with a long history of angina pectoris who have had repeated myocardial infarctions earlier. Recurrent macro-focal myocardial infarctions were more often noted in younger patients with a brief coronary history, their primary infarction having been of a micro-focal nature. In both groups of patients congestive cardiac insufficiency and pulmonary oedema were often noted. Cardiogenic shock was mainly seen in those with relapses of macro-focal myocardial infarction. Recurrent microfocal myocardial infarction was often characterized by the development of rhythm and conductivity disorders and high mortality rate, especially when the recurrence was of a macro-focal type."} {"id": "PMID:1271628", "title": "[Fast diagnosis of hemodynamic disorders in patients with heart disease].", "content": "The informativeness of arterial pressure, central venous pressure, cardiac contractions rate in the diagnosis of blood volume disorders combined with cardiac failure was studied in cardiac patients. The examination was carried out in 150 patients 80 of whom had been operated on the heart, mainly under extracorporeal circulation. The most informative parameter appeared to be the central venous pressure. An express-index is introduced that permits to differentiate between the following states: \"isolated\" hypovolemia, hypovolemia combined with cardiac failure combined with normovolemia, cardiac failure combined with hypervolemia.", "contents": "[Fast diagnosis of hemodynamic disorders in patients with heart disease]. The informativeness of arterial pressure, central venous pressure, cardiac contractions rate in the diagnosis of blood volume disorders combined with cardiac failure was studied in cardiac patients. The examination was carried out in 150 patients 80 of whom had been operated on the heart, mainly under extracorporeal circulation. The most informative parameter appeared to be the central venous pressure. An express-index is introduced that permits to differentiate between the following states: \"isolated\" hypovolemia, hypovolemia combined with cardiac failure combined with normovolemia, cardiac failure combined with hypervolemia."} {"id": "PMID:1271629", "title": "[Utilization of the thermodilution method for study and assessment of rapid changes in central hemodynamics under clinical conditions].", "content": "The authors report of the employment of the thermodilution method for repeated serial measurements of the cardiac output in 60 patients during Fentanyl -- Epontol induction anaesthesia conducted in accordance with Darbinyan's technique. The concept is illustrated by the data obtained during heart catheterization in 38 cases of congenital and acquired heart diseases, various myocardiopathies. The authors describe the technical aspects of the method. With proper technical facilities available, the method of thermodilution proves accessible, simple, precise and safe for the examination of cardiac output.", "contents": "[Utilization of the thermodilution method for study and assessment of rapid changes in central hemodynamics under clinical conditions]. The authors report of the employment of the thermodilution method for repeated serial measurements of the cardiac output in 60 patients during Fentanyl -- Epontol induction anaesthesia conducted in accordance with Darbinyan's technique. The concept is illustrated by the data obtained during heart catheterization in 38 cases of congenital and acquired heart diseases, various myocardiopathies. The authors describe the technical aspects of the method. With proper technical facilities available, the method of thermodilution proves accessible, simple, precise and safe for the examination of cardiac output."} {"id": "PMID:1271630", "title": "[Comparative assessment of data of echocardiography and phonocardiography in the diagnosis of heart diseases].", "content": "A comparison was made between the echo- and phonocardiographic examinations and the final clinical diagnosis of 85 patients with various cardiac pathology. Echo- and phonocardiography were found to be not alternative, and the less -- contradictory, but mutually supplementing methods. Echocardiography has certain advantages over phonocardiography in the diagnosis of mitral valve defects -- in evaluating the degree of its stenosis and in characterizing the morphological changes of the valve, but it is somewhat inferior in diagnosing mitral insufficiency. In the diagnosis of aortic valve defects phonocardiography appears to be more informative since echocardiography does not always permit to record the state of the aortic valve. Indisputable advantages of echocardiography in the diagnosis of the tricuspid valve defects were revealed. The comparison of the data of echocardiography and phonocardiography permitted to decypher the syndrome of \"a late systolic click with a late systolic murmur\" that was previously interpreted as a pericardium sound. Besides, the echocardiographic data on the changes in the left ventricular outflow tract help to explain the origin of the spindle-form systolic murmur. So far their interpretation was rather complicated, although they are often seen on phonocardiograms of normal individuals and patients with heart diseases.", "contents": "[Comparative assessment of data of echocardiography and phonocardiography in the diagnosis of heart diseases]. A comparison was made between the echo- and phonocardiographic examinations and the final clinical diagnosis of 85 patients with various cardiac pathology. Echo- and phonocardiography were found to be not alternative, and the less -- contradictory, but mutually supplementing methods. Echocardiography has certain advantages over phonocardiography in the diagnosis of mitral valve defects -- in evaluating the degree of its stenosis and in characterizing the morphological changes of the valve, but it is somewhat inferior in diagnosing mitral insufficiency. In the diagnosis of aortic valve defects phonocardiography appears to be more informative since echocardiography does not always permit to record the state of the aortic valve. Indisputable advantages of echocardiography in the diagnosis of the tricuspid valve defects were revealed. The comparison of the data of echocardiography and phonocardiography permitted to decypher the syndrome of \"a late systolic click with a late systolic murmur\" that was previously interpreted as a pericardium sound. Besides, the echocardiographic data on the changes in the left ventricular outflow tract help to explain the origin of the spindle-form systolic murmur. So far their interpretation was rather complicated, although they are often seen on phonocardiograms of normal individuals and patients with heart diseases."} {"id": "PMID:1271688", "title": "[Resistance testing of cytostatic agents on human tumors (author's transl)].", "content": "An in vitro short term incubation of human tumors with different cytostatic agents and their corresponding radioactive precursors of cell metabolism allows detection of those drugs which are inefficacious on the examined tumor. The pretherapeutical knowledge of those substances keeps the patient from unnecessary and damaging cytotoxic treatment. The in vitro and in vivo correlation of this technique was tested on 3 different groups of tumor patients: 1. Chemotherapeutically treated tumor patients with primary or secondary induced resistance against the applied cytostatic agents: all substances which clinically did not influence the tumor growth at the moment of the test also were inefficient in the in vitro test system. 2. Tumor patients who were treated according to a clinical therapy regimen contrary to the results of the in vitro testing: corresponding to the test, no influence on tumor growth was seen. 3. Tumor patients who were treated according to the results of the resistance test: after 8 weeks observation none of these patients had any signs of tumor progression.", "contents": "[Resistance testing of cytostatic agents on human tumors (author's transl)]. An in vitro short term incubation of human tumors with different cytostatic agents and their corresponding radioactive precursors of cell metabolism allows detection of those drugs which are inefficacious on the examined tumor. The pretherapeutical knowledge of those substances keeps the patient from unnecessary and damaging cytotoxic treatment. The in vitro and in vivo correlation of this technique was tested on 3 different groups of tumor patients: 1. Chemotherapeutically treated tumor patients with primary or secondary induced resistance against the applied cytostatic agents: all substances which clinically did not influence the tumor growth at the moment of the test also were inefficient in the in vitro test system. 2. Tumor patients who were treated according to a clinical therapy regimen contrary to the results of the in vitro testing: corresponding to the test, no influence on tumor growth was seen. 3. Tumor patients who were treated according to the results of the resistance test: after 8 weeks observation none of these patients had any signs of tumor progression."} {"id": "PMID:1271689", "title": "[Determination of creatine kinase-MB in serum using inhibiting antibodies (author's transl)].", "content": "A new method for the determination of creatine kinase-MB activity in the serum is presented. The principle of this method is the direct measurement of the activity of creatine kinase M subunits by inhibiting antibodies. The total test procedure takes 15 min. In the sera of all the 83 patients tested, who have clinically proven myocard infarction, creatine kinase-MB activity can be measured between the 6th and 28th hour after infarction. At the time of maximum total creatine kinase activity the percentage of creatine kinase-MB activity is between 6 and 17%, the mean value being 8%. In cases of emergency this method can be used for the differential diagnosis of elevated total creatine kinase activities of unknown origin.", "contents": "[Determination of creatine kinase-MB in serum using inhibiting antibodies (author's transl)]. A new method for the determination of creatine kinase-MB activity in the serum is presented. The principle of this method is the direct measurement of the activity of creatine kinase M subunits by inhibiting antibodies. The total test procedure takes 15 min. In the sera of all the 83 patients tested, who have clinically proven myocard infarction, creatine kinase-MB activity can be measured between the 6th and 28th hour after infarction. At the time of maximum total creatine kinase activity the percentage of creatine kinase-MB activity is between 6 and 17%, the mean value being 8%. In cases of emergency this method can be used for the differential diagnosis of elevated total creatine kinase activities of unknown origin."} {"id": "PMID:1271690", "title": "Increased consumption of refined carbohydrates in patients with Crohn's disease.", "content": "The nutritional habits of 63 patients with Crohn's disease (C.d.) were explored by means of questionnaires and compared with a control group of 63 persons matched as to age, sex and social status. Before the disease was recognized patients with C.d. consumed 742 grams/week (g/w) sweets and 1380 g/w pastries, during the disease 482 g/w sweets and 905 g/w pastries. The controls only consumed 285 g/w sweets and 563 g/w pastries. The differences between both groups are highly significant. There existed no significant difference in the intake of other foodstuffs such as proteins, fats, vegetables or alcohol. The high intake of refined carbohydrates in patients with C.d. may be partly responsible for its increasing incidence in the developed countries. This might be due to the sugar content as such and/or the food additives.", "contents": "Increased consumption of refined carbohydrates in patients with Crohn's disease. The nutritional habits of 63 patients with Crohn's disease (C.d.) were explored by means of questionnaires and compared with a control group of 63 persons matched as to age, sex and social status. Before the disease was recognized patients with C.d. consumed 742 grams/week (g/w) sweets and 1380 g/w pastries, during the disease 482 g/w sweets and 905 g/w pastries. The controls only consumed 285 g/w sweets and 563 g/w pastries. The differences between both groups are highly significant. There existed no significant difference in the intake of other foodstuffs such as proteins, fats, vegetables or alcohol. The high intake of refined carbohydrates in patients with C.d. may be partly responsible for its increasing incidence in the developed countries. This might be due to the sugar content as such and/or the food additives."} {"id": "PMID:1271691", "title": "[Effect of hyperventilation on cerebral blood flow and metabolism in man; continuous monitoring of arterio-cerebral venous glucose differences (author's transl)].", "content": "CBF decreases when arterial PCO2 is lowered by physiological, pathological or therapeutically induced hyperventilation. This is accompanied by an undelayed compensatory increase of oxygen-av-differences. Continuous monitoring of enzymatically determined glucose-av-differences of the brain during hyperventilation has for the first time shown that there is an undelayed fall of the cerebral venous glucose content, too. This indicates that the brain cells extract an augmented amount of glucose per ml blood during decreased CBF. Therefore glucose metabolism of the brain is not impaired during non-critical CBF reduction. However, when arterial PCO2 falls below 25 mmHg a detrimental effect on CBF and cerebral metabolism has to be expected. CBF will then decrease below the critical threshold for an undisturbed oxygen supply, and the respiratory alcalosis will lead to a disturbed oxygen delivery due to the Bohr-effect. As a consequence both of these factors will reduce the energy-yielding oxydative glycolysis and augment the little energy producing anaerobic glycolysis with a concomitant increase of lactate formation, resulting in a tissue and spinal fluid lactate acidosis. From our results it is therefore concluded that induced hyperventilation should be avoided, and that central hyperventilation in diseased states has to be considered as an additional threat to the brain.", "contents": "[Effect of hyperventilation on cerebral blood flow and metabolism in man; continuous monitoring of arterio-cerebral venous glucose differences (author's transl)]. CBF decreases when arterial PCO2 is lowered by physiological, pathological or therapeutically induced hyperventilation. This is accompanied by an undelayed compensatory increase of oxygen-av-differences. Continuous monitoring of enzymatically determined glucose-av-differences of the brain during hyperventilation has for the first time shown that there is an undelayed fall of the cerebral venous glucose content, too. This indicates that the brain cells extract an augmented amount of glucose per ml blood during decreased CBF. Therefore glucose metabolism of the brain is not impaired during non-critical CBF reduction. However, when arterial PCO2 falls below 25 mmHg a detrimental effect on CBF and cerebral metabolism has to be expected. CBF will then decrease below the critical threshold for an undisturbed oxygen supply, and the respiratory alcalosis will lead to a disturbed oxygen delivery due to the Bohr-effect. As a consequence both of these factors will reduce the energy-yielding oxydative glycolysis and augment the little energy producing anaerobic glycolysis with a concomitant increase of lactate formation, resulting in a tissue and spinal fluid lactate acidosis. From our results it is therefore concluded that induced hyperventilation should be avoided, and that central hyperventilation in diseased states has to be considered as an additional threat to the brain."} {"id": "PMID:1271692", "title": "[The effect of potassium on ouabain-binding to human cardiac cell membranes (author's transl)].", "content": "The concentration of cardiac glycosides in the serum of an individual patient does not necessarily correlate strictly with the known effects or side effects of these drugs. It is good clinical experience for instance that an acutely decreased serum potassium concentration due to diuretic therapy or dialysis may cause severe digitalis-induced arrhythmias in spite of an unchanged serum glycoside level. On the other hand digitalis intoxication often is treated successfully by the application of potassium. These observations prompted us to investigate the specific binding of tritiated g-strophanthin to isolated human cardiac cell membranes in the presence of different potassium concentrations. Potassium in a concentration-dependent manner displaces ouabain from its binding sites by decreasing the affinity of the receptor for the drug. However, the number of receptor sites remains constant. When analysing the association and dissociation rates of the ouabain-receptor complex it was found that potassium inhibits the binding process only, without affecting the dissociation. At least up to a concentration of 5 mM the potassium induced displacement of ouabain from its binding sites seems to be competitive. These in vitro measurements of the strophanthin--receptor interactions agree with clinical observations and are helpful in their explanation.", "contents": "[The effect of potassium on ouabain-binding to human cardiac cell membranes (author's transl)]. The concentration of cardiac glycosides in the serum of an individual patient does not necessarily correlate strictly with the known effects or side effects of these drugs. It is good clinical experience for instance that an acutely decreased serum potassium concentration due to diuretic therapy or dialysis may cause severe digitalis-induced arrhythmias in spite of an unchanged serum glycoside level. On the other hand digitalis intoxication often is treated successfully by the application of potassium. These observations prompted us to investigate the specific binding of tritiated g-strophanthin to isolated human cardiac cell membranes in the presence of different potassium concentrations. Potassium in a concentration-dependent manner displaces ouabain from its binding sites by decreasing the affinity of the receptor for the drug. However, the number of receptor sites remains constant. When analysing the association and dissociation rates of the ouabain-receptor complex it was found that potassium inhibits the binding process only, without affecting the dissociation. At least up to a concentration of 5 mM the potassium induced displacement of ouabain from its binding sites seems to be competitive. These in vitro measurements of the strophanthin--receptor interactions agree with clinical observations and are helpful in their explanation."} {"id": "PMID:1271693", "title": "Serum digoxin concentration and half-life in newborn.", "content": "Serum digoxin concentration and half-life were radioimmunologically determined in 9 mature newborns after 7 days medication with digoxin. The newborns were in respiratory distress treated with continuous positive airway pressure or were suspected to have serious congenital heart disease. Loading dose was 26 mug/kg body weight intravenously and 35 mug/kg body weight orally, respectively. Maintenance dose corresponded to 1/8th of the digitalization dose twice daily. The serum digoxin level 12 h after the last dose varied between 1.4 and 2.5 ng/ml (mean 2.0 ng/ml, Sx=0.4). The serum half-life of digoxin varied between 21.7 and 42.4 h (mean 30.0 h, Sx=7.7). The mean serum half-life of digoxin of 30 h attained values found in adults without renal disease. This suggests that the serum digoxin levels of newborns which are usually higher if compared with those of adults result from higher digoxin doses per unit body weight and not from diminished digoxin elimination.", "contents": "Serum digoxin concentration and half-life in newborn. Serum digoxin concentration and half-life were radioimmunologically determined in 9 mature newborns after 7 days medication with digoxin. The newborns were in respiratory distress treated with continuous positive airway pressure or were suspected to have serious congenital heart disease. Loading dose was 26 mug/kg body weight intravenously and 35 mug/kg body weight orally, respectively. Maintenance dose corresponded to 1/8th of the digitalization dose twice daily. The serum digoxin level 12 h after the last dose varied between 1.4 and 2.5 ng/ml (mean 2.0 ng/ml, Sx=0.4). The serum half-life of digoxin varied between 21.7 and 42.4 h (mean 30.0 h, Sx=7.7). The mean serum half-life of digoxin of 30 h attained values found in adults without renal disease. This suggests that the serum digoxin levels of newborns which are usually higher if compared with those of adults result from higher digoxin doses per unit body weight and not from diminished digoxin elimination."} {"id": "PMID:1271694", "title": "[On thyroid phosphatase in human serum (author's transl)].", "content": "Patients with hyperthyreoidism often present an increased activity of alkaline phosphatase in serum. Determination of isoenzymes may help to assign to different organs an elevated enzyme-activity in serum. This report deals with a patient suffering from hyperthyreoidism. In his serum alkaline phosphatase of the thyroid gland could be identified by comparison with organ-extracts. Raised activity of this isoenzyme can contribute besides bone, liver and small bowel to the increased serum-activity of total alkaline phosphatase in patients with hyperthyreoidism.", "contents": "[On thyroid phosphatase in human serum (author's transl)]. Patients with hyperthyreoidism often present an increased activity of alkaline phosphatase in serum. Determination of isoenzymes may help to assign to different organs an elevated enzyme-activity in serum. This report deals with a patient suffering from hyperthyreoidism. In his serum alkaline phosphatase of the thyroid gland could be identified by comparison with organ-extracts. Raised activity of this isoenzyme can contribute besides bone, liver and small bowel to the increased serum-activity of total alkaline phosphatase in patients with hyperthyreoidism."} {"id": "PMID:1271695", "title": "[Dietary problems in the management of type I hyperlipoproteinemia (author's transl)].", "content": "The therapeutic effect of different diets varying in long chain and medium chain triglycerides, carbohydrate, and protein was tested in two siblings with type I hyperlipoproteinemia. Despite administration of an extremely fat reduced diet ( less than 5 g daily), a normalization of plasma TG could not be obtained because-as a consequence of its high carbohydrate and/or its MCT content-it resulted in a considerable increase in pre-beta-lipoproteins. As life long dietary therapy has to be maintained, the risks of a normal therapy has to be maintained, the risks of a normal fat containing diet (mainly bouts of pancreatitis) and those of a carbohydrate and MCT rich diet (premature atherosclerosis) are to be carefully considered. On the basis of our data we therefore suggest the following dietary regimen: 1. Reduced intake of long chain triglycerides (less than 30 gms per day), but with sufficient amounts of essential fatty acids (4-6 gms linoleate daily). 2. The carbohydrates should not exceed 50% of total calories and ought to consist mainly of starch. 3. The caloric deficit thus generated should be balanced by a high protein intake. This is faciliated by applying a specially protein-enriched food. 4. Medium chanin triglycerides may be necessary when adherence to the protein-rich diet turns out to be bad.", "contents": "[Dietary problems in the management of type I hyperlipoproteinemia (author's transl)]. The therapeutic effect of different diets varying in long chain and medium chain triglycerides, carbohydrate, and protein was tested in two siblings with type I hyperlipoproteinemia. Despite administration of an extremely fat reduced diet ( less than 5 g daily), a normalization of plasma TG could not be obtained because-as a consequence of its high carbohydrate and/or its MCT content-it resulted in a considerable increase in pre-beta-lipoproteins. As life long dietary therapy has to be maintained, the risks of a normal therapy has to be maintained, the risks of a normal fat containing diet (mainly bouts of pancreatitis) and those of a carbohydrate and MCT rich diet (premature atherosclerosis) are to be carefully considered. On the basis of our data we therefore suggest the following dietary regimen: 1. Reduced intake of long chain triglycerides (less than 30 gms per day), but with sufficient amounts of essential fatty acids (4-6 gms linoleate daily). 2. The carbohydrates should not exceed 50% of total calories and ought to consist mainly of starch. 3. The caloric deficit thus generated should be balanced by a high protein intake. This is faciliated by applying a specially protein-enriched food. 4. Medium chanin triglycerides may be necessary when adherence to the protein-rich diet turns out to be bad."} {"id": "PMID:1271696", "title": "[Blood coagulation and fibrinolysis in women receiving estrogen, gestagen and estrogen-gestagen-contraceptives (author's transl)].", "content": "Eight femal subjects received a contraceptive with a low estrogen content (Neogynon), the estrogen component (50 mug ethinylestradiol) and consecutively the gestagen component (250 mug D-Norgestrel) of the contraceptive. Each treatment cycle was followed by a control cycle. At various times of the control and therapy cycles several coagulation and fibrinolytic parameters were investigated. Statistical analyses were performed by multivariate two-factorial analysis of variance. Plasminogen exhibities a statistically significant increase during the treatment with ethinylestradiol and the combination of this steroid with D-norgestrel. No significant changes were found for all other parameters, including partial thromboplastin time, fibriogen, factors X, IX, VIII, factor VIII-related antigen, antithrombin III and fibrin(ogen)degradation products.", "contents": "[Blood coagulation and fibrinolysis in women receiving estrogen, gestagen and estrogen-gestagen-contraceptives (author's transl)]. Eight femal subjects received a contraceptive with a low estrogen content (Neogynon), the estrogen component (50 mug ethinylestradiol) and consecutively the gestagen component (250 mug D-Norgestrel) of the contraceptive. Each treatment cycle was followed by a control cycle. At various times of the control and therapy cycles several coagulation and fibrinolytic parameters were investigated. Statistical analyses were performed by multivariate two-factorial analysis of variance. Plasminogen exhibities a statistically significant increase during the treatment with ethinylestradiol and the combination of this steroid with D-norgestrel. No significant changes were found for all other parameters, including partial thromboplastin time, fibriogen, factors X, IX, VIII, factor VIII-related antigen, antithrombin III and fibrin(ogen)degradation products."} {"id": "PMID:1271697", "title": "[Electronmicroscopic visualization of virusparticles in cases of gastroenteritis of infants and children (author's transl)].", "content": "In 72 faecal extracts examined from babies and infants with an acute gastroenteritis, virus particles were found in 29 cases. These particles could be classified as reovirus-like in 16 cases, coronaviruses in 11 cases and adenoviruses in 2 cases. The electron microscopic investigation of 11 faecal extracts from healthy babies did not show any of these particles. Comparative studies on the concentration methods were performed.", "contents": "[Electronmicroscopic visualization of virusparticles in cases of gastroenteritis of infants and children (author's transl)]. In 72 faecal extracts examined from babies and infants with an acute gastroenteritis, virus particles were found in 29 cases. These particles could be classified as reovirus-like in 16 cases, coronaviruses in 11 cases and adenoviruses in 2 cases. The electron microscopic investigation of 11 faecal extracts from healthy babies did not show any of these particles. Comparative studies on the concentration methods were performed."} {"id": "PMID:1271698", "title": "[Kinetics of sulfobromophtalein using albumin-bound BSP (author's transl)].", "content": "BSP-kinetics are examined after adding different quantities of albumine to the solution to be injected. At a dosis of 5 mg BSP per kg body weight no changes are observed in the elimination half-life up to a BSP-albumine ratio of 1:10, at larger albumine dosis the value is prolonged.", "contents": "[Kinetics of sulfobromophtalein using albumin-bound BSP (author's transl)]. BSP-kinetics are examined after adding different quantities of albumine to the solution to be injected. At a dosis of 5 mg BSP per kg body weight no changes are observed in the elimination half-life up to a BSP-albumine ratio of 1:10, at larger albumine dosis the value is prolonged."} {"id": "PMID:1271732", "title": "Hemoglobins of the opossum (Didelphis virginiana Kerr). I. Developmental changes from yolk sac to definitive erythropoiesis.", "content": "In 5- to 7-da old opossum pouch young, hemoglobins were observed. The \"primitive\" species I, II, and IV were shown to be electrophoretically distinct from the adult hemoglobin III. Hemoglobin I was detectable until the 7th postnatal da. Hemoglobins I, II, and IV were detected only during the period when yolk sac-derived primitive erythroblasts were seen in circulation, ei, until the 13th postnatal da, but in decreased amounts from the 6th to 13th da. The electrophoretic pattern of hemoglobin of pouch young after the 13th postnatal da was indistinguishable from that of the adult opossum.", "contents": "Hemoglobins of the opossum (Didelphis virginiana Kerr). I. Developmental changes from yolk sac to definitive erythropoiesis. In 5- to 7-da old opossum pouch young, hemoglobins were observed. The \"primitive\" species I, II, and IV were shown to be electrophoretically distinct from the adult hemoglobin III. Hemoglobin I was detectable until the 7th postnatal da. Hemoglobins I, II, and IV were detected only during the period when yolk sac-derived primitive erythroblasts were seen in circulation, ei, until the 13th postnatal da, but in decreased amounts from the 6th to 13th da. The electrophoretic pattern of hemoglobin of pouch young after the 13th postnatal da was indistinguishable from that of the adult opossum."} {"id": "PMID:1271734", "title": "An evaluation of sedatives and anesthetics in the agouti (Dasyprocta sp).", "content": "Seven drugs administered im were evaluated to determine their efficacy in immobilizing captive agoutis. Ketamine HCl (63-83 mg/kg) and phencyclidine HCl (16.5-22.0 mg/kg) produced immobilization and analgesia. Phencyclidine administration was accompanied by numerous side effects and prolonged recovery. Xylazine HCl (3-70 mg/kg) and fentanyl-droperidol (0.28-1.11 ml/kg( produced varying degrees of ataxia and intermittent recumbency. Acetylpromazine, chlorpromazine, and promazine HCl were ineffective. Surgical anesthesia was successfully induced and maintained with halothane.", "contents": "An evaluation of sedatives and anesthetics in the agouti (Dasyprocta sp). Seven drugs administered im were evaluated to determine their efficacy in immobilizing captive agoutis. Ketamine HCl (63-83 mg/kg) and phencyclidine HCl (16.5-22.0 mg/kg) produced immobilization and analgesia. Phencyclidine administration was accompanied by numerous side effects and prolonged recovery. Xylazine HCl (3-70 mg/kg) and fentanyl-droperidol (0.28-1.11 ml/kg( produced varying degrees of ataxia and intermittent recumbency. Acetylpromazine, chlorpromazine, and promazine HCl were ineffective. Surgical anesthesia was successfully induced and maintained with halothane."} {"id": "PMID:1271735", "title": "Birth sequence in mice.", "content": "Succession of deliveries at parturition was determined in mice following a marker injection in utero. The data failed to refute the hypothesis of a random birth order, as delivery from either uterine horn was found to be unpredictable. In addition, significantly more females delivered the first pup from the right uterine horn, supporting the concept of a \"physiological dominance\" for the right side of the mouse reproductive tract.", "contents": "Birth sequence in mice. Succession of deliveries at parturition was determined in mice following a marker injection in utero. The data failed to refute the hypothesis of a random birth order, as delivery from either uterine horn was found to be unpredictable. In addition, significantly more females delivered the first pup from the right uterine horn, supporting the concept of a \"physiological dominance\" for the right side of the mouse reproductive tract."} {"id": "PMID:1271736", "title": "Thiamin status of laboratory rabbits.", "content": "Measurements of blood thiamin concentration, erythrocyte transketolase (TK) activity, and stomach and cecal thiamin concentration were made in 10 normal New Zealand white rabbits consuming a commercial pelleted rabbit diet. The concentration of the vitamin was somewhat higher in stomach content (57.2 +/- 11.8 m mug/g) than in cecal content (38.5 +/- 14.9 mmug/g). Erythrocyte TK activity was well within the range reported as normal in other mammalian species (TPP effect=2.6% for hexose and 0.5% for pentose).", "contents": "Thiamin status of laboratory rabbits. Measurements of blood thiamin concentration, erythrocyte transketolase (TK) activity, and stomach and cecal thiamin concentration were made in 10 normal New Zealand white rabbits consuming a commercial pelleted rabbit diet. The concentration of the vitamin was somewhat higher in stomach content (57.2 +/- 11.8 m mug/g) than in cecal content (38.5 +/- 14.9 mmug/g). Erythrocyte TK activity was well within the range reported as normal in other mammalian species (TPP effect=2.6% for hexose and 0.5% for pentose)."} {"id": "PMID:1271737", "title": "A new castration technic in the guinea pig.", "content": "A castration technic was perfected for removing seminiferous tubules and Leydig cells from the tunica albuginea, leaving the epididymis and its nerve and vascular supplies intact. There was a significant decrease in seminal vesicle weight in 15 guinea pigs castrated by this new procedure, indicating that the testicular androgen source was removed during castration. Spermatozoa remained motile in the ductus deferens of 18 animals that had been castrated for periods ranging from 7-70 da. The longevity of spermatozoa in the excurrent ducts was attributed to minimal trauma and damage to the ducts and their vascular and nvere supplies using this new technic.", "contents": "A new castration technic in the guinea pig. A castration technic was perfected for removing seminiferous tubules and Leydig cells from the tunica albuginea, leaving the epididymis and its nerve and vascular supplies intact. There was a significant decrease in seminal vesicle weight in 15 guinea pigs castrated by this new procedure, indicating that the testicular androgen source was removed during castration. Spermatozoa remained motile in the ductus deferens of 18 animals that had been castrated for periods ranging from 7-70 da. The longevity of spermatozoa in the excurrent ducts was attributed to minimal trauma and damage to the ducts and their vascular and nvere supplies using this new technic."} {"id": "PMID:1271738", "title": "Development of an animal model for Mycoplasma-related reproductive failure.", "content": "Pregnant hamsters and mice were injected ip with various doses of Mycoplasma hominis, M fermentans, and M arthritidis, all of which may have a potential role in human or animal reproductive failure. Inoculations were made near the completion of each trimester, and the products of conception were removed by hysterectomy 24 hr before anticipated delivery. Resorptions and birth defects were tabulated. Preliminary data on 1869 fetuses indicate that BALB mice merit further evaluation as a possible model for mycoplasma-related reproductive failure.", "contents": "Development of an animal model for Mycoplasma-related reproductive failure. Pregnant hamsters and mice were injected ip with various doses of Mycoplasma hominis, M fermentans, and M arthritidis, all of which may have a potential role in human or animal reproductive failure. Inoculations were made near the completion of each trimester, and the products of conception were removed by hysterectomy 24 hr before anticipated delivery. Resorptions and birth defects were tabulated. Preliminary data on 1869 fetuses indicate that BALB mice merit further evaluation as a possible model for mycoplasma-related reproductive failure."} {"id": "PMID:1271739", "title": "A new technic for obtaining blood from mice.", "content": "A practical technic was described for collecting serial blood samples from mice. Blood was obtained from a tail incision made immediately after the mice had been exposed to an ambient temperature of 45 degrees C. Individual samples sufficient for most tests were readily obtained without significant hemolysis. The technic was rapid, reliable, humane, and required no special skill.", "contents": "A new technic for obtaining blood from mice. A practical technic was described for collecting serial blood samples from mice. Blood was obtained from a tail incision made immediately after the mice had been exposed to an ambient temperature of 45 degrees C. Individual samples sufficient for most tests were readily obtained without significant hemolysis. The technic was rapid, reliable, humane, and required no special skill."} {"id": "PMID:1271740", "title": "Histopathologic changes in laboratory animals resulting from various methods of euthanasia.", "content": "The histopathologic changes caused by various methods of euthanosia were studied in rats, mice, guinea pigs, and rabbits. Lesions resulting from a particular methods of euthanasia were consistent from species to species. Each method studied affected the lungs to some degree, ranging from mild congestion of alveolar capillaries to marked intramural edema of pulmonary arteries and alteration of vascular permeability. Euthanasia of experimental animals by overexposure to CO2, or ip injection of concentrated sodium pentobarbital seemed most suitable for pulmonary studies. Decapitation (mice, rats, guinea pigs), cervical dislocation (mice), CO2, and intracardial injection of sodium pentobarbital were more suitable for examination of abdominal viscera.", "contents": "Histopathologic changes in laboratory animals resulting from various methods of euthanasia. The histopathologic changes caused by various methods of euthanosia were studied in rats, mice, guinea pigs, and rabbits. Lesions resulting from a particular methods of euthanasia were consistent from species to species. Each method studied affected the lungs to some degree, ranging from mild congestion of alveolar capillaries to marked intramural edema of pulmonary arteries and alteration of vascular permeability. Euthanasia of experimental animals by overexposure to CO2, or ip injection of concentrated sodium pentobarbital seemed most suitable for pulmonary studies. Decapitation (mice, rats, guinea pigs), cervical dislocation (mice), CO2, and intracardial injection of sodium pentobarbital were more suitable for examination of abdominal viscera."} {"id": "PMID:1271741", "title": "Improved caging for nine-banded armadillos.", "content": "Impact resistant polyethylene cages were evaluated in these laboratories as replacements for plywood boxes for housing nine-banded armadillos. They were found to be less expensive, easier to sanitize, and to require less than one-third as much floor space per animal as the boxes. This innovation has made it practical to house large numbers of armadillos economically and conveniently in almost any animal facility.", "contents": "Improved caging for nine-banded armadillos. Impact resistant polyethylene cages were evaluated in these laboratories as replacements for plywood boxes for housing nine-banded armadillos. They were found to be less expensive, easier to sanitize, and to require less than one-third as much floor space per animal as the boxes. This innovation has made it practical to house large numbers of armadillos economically and conveniently in almost any animal facility."} {"id": "PMID:1271743", "title": "Levels of spontaneous malformations in the CD rat and the CD-1 mouse.", "content": "Extensive information was supplied about the frequencies and types of spontaneous skeletal and visceral malformations in control and test fetuses which may be encountered during teratological assays. Data were also provided on fertility, agerage body weights, water consumption as a function of diet, and food consumption. The two strains used, Crl:COBS CD (SD) BR (France) rats and Crl:CD-1 (ICR) BR (France) mice, are valuable research tools since they are prolific, have a low rate of spontaneous malformations, and are responsive to teratogenic agents. The difficulties of determining the significance of infrequent anomalies were discussed.", "contents": "Levels of spontaneous malformations in the CD rat and the CD-1 mouse. Extensive information was supplied about the frequencies and types of spontaneous skeletal and visceral malformations in control and test fetuses which may be encountered during teratological assays. Data were also provided on fertility, agerage body weights, water consumption as a function of diet, and food consumption. The two strains used, Crl:COBS CD (SD) BR (France) rats and Crl:CD-1 (ICR) BR (France) mice, are valuable research tools since they are prolific, have a low rate of spontaneous malformations, and are responsive to teratogenic agents. The difficulties of determining the significance of infrequent anomalies were discussed."} {"id": "PMID:1271744", "title": "Current experience using the laboratory rat in aging studies.", "content": "The breeding and maintenance conditions for 2 strains of inbred rats, the WAG/Rij and BN/Bi rats, were described. The survival characteristics of these 2 strains were compared with those of 2 other experiments in which rats were kept for longevity studies under different environmental conditions of microbiologic status and diet. Data were provided on the rate and types of spontaneous tumors found in these 2 rat strains. It can be concluded that in order to obtain rats of good quality and in sufficient numbers for aging studies, breeding and raising the animals under strict SPF conditions is warranted. It is also necessary to maintain them under \"clean conventional\" conditions for long-term studies.", "contents": "Current experience using the laboratory rat in aging studies. The breeding and maintenance conditions for 2 strains of inbred rats, the WAG/Rij and BN/Bi rats, were described. The survival characteristics of these 2 strains were compared with those of 2 other experiments in which rats were kept for longevity studies under different environmental conditions of microbiologic status and diet. Data were provided on the rate and types of spontaneous tumors found in these 2 rat strains. It can be concluded that in order to obtain rats of good quality and in sufficient numbers for aging studies, breeding and raising the animals under strict SPF conditions is warranted. It is also necessary to maintain them under \"clean conventional\" conditions for long-term studies."} {"id": "PMID:1271745", "title": "Histological and histochemical studies of myocardial lesions in BALBc/Cr mice.", "content": "Myocardial lesions were noticed in BALBc/Cr mice during experiments with Moloney sarcoma virus (MSV). A study was initiated using unifected BALBc/Cr mice to determine whether these lesions were the result of a viral infection. Sixty percent of the females and 30% of the males used were found to have macroscopic lesions (mainly white spots on the right ventricle). The reported lesions were studied both histologically and histochemically. The animals were also examined for parasites such as Toxoplasma and tapeworm larvae, and were found negative. The investigation, which is still in progress, demonstrates the spontaneity of myocardial lesions in BALBc/Cr mice.", "contents": "Histological and histochemical studies of myocardial lesions in BALBc/Cr mice. Myocardial lesions were noticed in BALBc/Cr mice during experiments with Moloney sarcoma virus (MSV). A study was initiated using unifected BALBc/Cr mice to determine whether these lesions were the result of a viral infection. Sixty percent of the females and 30% of the males used were found to have macroscopic lesions (mainly white spots on the right ventricle). The reported lesions were studied both histologically and histochemically. The animals were also examined for parasites such as Toxoplasma and tapeworm larvae, and were found negative. The investigation, which is still in progress, demonstrates the spontaneity of myocardial lesions in BALBc/Cr mice."} {"id": "PMID:1271746", "title": "Advances in animal care technology at the National Center for Toxicological Research.", "content": "The research purpose of the NCTR as it relates to animal care emphasizes the improvement of protocols for safety assessments, the study of irreversible lesions, and the use of valid animal models. The development, building, and operation of the \"A\" Barrier were described. The \"A\" Barrier is a complex of equipment, instrumentation, and rooms with controlled entry designed to prevent introduction of microoranisms or environmental factors into the SPF animal colonies. Support facilities such as computer controls and pathology were also described. The first experimental compound being tested is 2-acetylaminofluorene (2-AAF) which will be administered to a total of 25,000 mice in some 72 different treatment groups at 7 dose levels. The desired end-product of the center is to produce a series of tests which can be done quickly, efficiently, and economically and allow for a realistic estimate of risk to man of suspected toxic chemicals.", "contents": "Advances in animal care technology at the National Center for Toxicological Research. The research purpose of the NCTR as it relates to animal care emphasizes the improvement of protocols for safety assessments, the study of irreversible lesions, and the use of valid animal models. The development, building, and operation of the \"A\" Barrier were described. The \"A\" Barrier is a complex of equipment, instrumentation, and rooms with controlled entry designed to prevent introduction of microoranisms or environmental factors into the SPF animal colonies. Support facilities such as computer controls and pathology were also described. The first experimental compound being tested is 2-acetylaminofluorene (2-AAF) which will be administered to a total of 25,000 mice in some 72 different treatment groups at 7 dose levels. The desired end-product of the center is to produce a series of tests which can be done quickly, efficiently, and economically and allow for a realistic estimate of risk to man of suspected toxic chemicals."} {"id": "PMID:1271747", "title": "Progress report on the Charles River Breeding Laboratories' free-ranging rhesus monkey breeding colony on Key Lois, Florida.", "content": "The nucleus of a breeding colony of free-ranging rhesus monkeys (Macaca mulatta) free from tuberculosis, herpes-B virus, shigellosis, and salmonellosis has been established on Key Lois, Florida, USA. Standardized procedures for trapping, quarantine, and shipping from the wild in India to the island have been established. The monkeys seem to have adapted well to the Florida Keys' climate. Reproduction has proceeded according to expectations, and social groups have been formed with continual restructuring as each new group is placed on the island. The isolation of Key Lois from other inhabited keys by the open sea affords good isolation and has discouraged intrusion by unwanted visitors. The operational costs of this island breeding program are encouraging. It is projected that by 1976 or 1977, monkeys should be available from this colony at a lower price than for animals bred in indoor facilities; and their availability will be in excess of animals trapped in the forest and subjected to a conventional conditioning and quarantine period.", "contents": "Progress report on the Charles River Breeding Laboratories' free-ranging rhesus monkey breeding colony on Key Lois, Florida. The nucleus of a breeding colony of free-ranging rhesus monkeys (Macaca mulatta) free from tuberculosis, herpes-B virus, shigellosis, and salmonellosis has been established on Key Lois, Florida, USA. Standardized procedures for trapping, quarantine, and shipping from the wild in India to the island have been established. The monkeys seem to have adapted well to the Florida Keys' climate. Reproduction has proceeded according to expectations, and social groups have been formed with continual restructuring as each new group is placed on the island. The isolation of Key Lois from other inhabited keys by the open sea affords good isolation and has discouraged intrusion by unwanted visitors. The operational costs of this island breeding program are encouraging. It is projected that by 1976 or 1977, monkeys should be available from this colony at a lower price than for animals bred in indoor facilities; and their availability will be in excess of animals trapped in the forest and subjected to a conventional conditioning and quarantine period."} {"id": "PMID:1271748", "title": "Surface characteristics of normal and atherosclerotic human arteries including observations suggesting interaction between flow and intimal morphology.", "content": "High resolution casts of the femoral and coronary arteries were made at physiologic pressure in 44 cadavers. A magnifying surface and profile analyzer were used for examination of the small surface characteristics of the casts. Corresponding portions of the arterial wall were compared by gross and microscopic examination. In sections without pathologic evidence of atherosclerosis, the cast surface characteristically demonstrated small longitudinal plicae, similar in size to those previously reported in studies with the scanning electron microscope. With increasing degrees of intimal thickening and atherosclerosis, longitudinal ridges were seen. In complete involvement of the intima, the ridge pattern was replaced by a locally smooth, grossly irregular surface. The orientation of ridges at curves and near branches and discrete plaques suggested the direction of secondary surface flow streamlines expected of these areas on the basis of hydrodynamic theory. Therefore, there may be formative interactions between blood flow and wall structure on a more local basis than previously surmised.", "contents": "Surface characteristics of normal and atherosclerotic human arteries including observations suggesting interaction between flow and intimal morphology. High resolution casts of the femoral and coronary arteries were made at physiologic pressure in 44 cadavers. A magnifying surface and profile analyzer were used for examination of the small surface characteristics of the casts. Corresponding portions of the arterial wall were compared by gross and microscopic examination. In sections without pathologic evidence of atherosclerosis, the cast surface characteristically demonstrated small longitudinal plicae, similar in size to those previously reported in studies with the scanning electron microscope. With increasing degrees of intimal thickening and atherosclerosis, longitudinal ridges were seen. In complete involvement of the intima, the ridge pattern was replaced by a locally smooth, grossly irregular surface. The orientation of ridges at curves and near branches and discrete plaques suggested the direction of secondary surface flow streamlines expected of these areas on the basis of hydrodynamic theory. Therefore, there may be formative interactions between blood flow and wall structure on a more local basis than previously surmised."} {"id": "PMID:1271749", "title": "Permeability alteration of sarcolemmal membrane in catecholamine-induced cardiac muscle cell injury. In vivo studies with fine structural diffusion tracer horse radish peroxidase.", "content": "Cardiac muscle cell injury was produced in male Sprague-Dawley rats weighing 300 to 450 gm. with catecholamines, norepinephrine, and isoproterenol; sarcolemmal membrane alteration was tested in vivo using the extracellular macromolecular tracer, horseradish peroxidase. Norepinephrine was administered in continuous intravenous infusion in a dose of 4 to 6 mug. per 100 gm. of body weight per minute, whereas isoproterenol was given as a single subcutaneous injection in a dose of 8.5 mg. per 100 gm. of body weight. Horseradish peroxidase was injected intravenously and localized in the right ventricular myocardium following 6 and 30 minutes of circulation time by light and electron microscopy. As early as 10 minutes after norepinephrine infusion, horseradish peroxidase appeared within cardiac muscle cells possessing normal fine structure. Selective deposition of the tracer on normal and altered myofilaments was noted. Similar observations were made in the isoproterenol model at 60 to 90 minutes. The results indicate that sarcolemmal membrane permeability alteration is an early event in catecholamine-induced cardiac muscle injury. The possible functional significance of the findings is discussed.", "contents": "Permeability alteration of sarcolemmal membrane in catecholamine-induced cardiac muscle cell injury. In vivo studies with fine structural diffusion tracer horse radish peroxidase. Cardiac muscle cell injury was produced in male Sprague-Dawley rats weighing 300 to 450 gm. with catecholamines, norepinephrine, and isoproterenol; sarcolemmal membrane alteration was tested in vivo using the extracellular macromolecular tracer, horseradish peroxidase. Norepinephrine was administered in continuous intravenous infusion in a dose of 4 to 6 mug. per 100 gm. of body weight per minute, whereas isoproterenol was given as a single subcutaneous injection in a dose of 8.5 mg. per 100 gm. of body weight. Horseradish peroxidase was injected intravenously and localized in the right ventricular myocardium following 6 and 30 minutes of circulation time by light and electron microscopy. As early as 10 minutes after norepinephrine infusion, horseradish peroxidase appeared within cardiac muscle cells possessing normal fine structure. Selective deposition of the tracer on normal and altered myofilaments was noted. Similar observations were made in the isoproterenol model at 60 to 90 minutes. The results indicate that sarcolemmal membrane permeability alteration is an early event in catecholamine-induced cardiac muscle injury. The possible functional significance of the findings is discussed."} {"id": "PMID:1271750", "title": "Effect of HgCl2 on rat kidney cells in primary culture.", "content": "Single cell suspensions, obtained from rat kidneys, were cultured with various concentrations of HgCl2 for different times to examine the effects on cellular synthetic activity. Unexpectedly, the RNA synthesis of kidney cells was stimulated with low doses of HgCl2, whereas it was inhibited with higher doses. Even at a higher dose, RNA synthesis was stimulated during early incubation but was inhibited during longer incubations. Thus, the effect of mercury showed a biphasic pattern both in dose-response and time-response relationships. Moreover, once the cells were exposed to HgCl2 for a certain period, RNA syntehsis was irreversibly inhibited. Since RNA synthesis was inhibited earlier than DNA or a protein synthesis, the RNA synthesizing system appeared most susceptible. Without HgCl2, by the time DNA synthesis reached its maximum, protein and RNA synthesis had already declined. In contrast, RNA synthesis of HgCl2-treated cells remained at its maximal level and showed no decline when DNA synthesis reached its peak.", "contents": "Effect of HgCl2 on rat kidney cells in primary culture. Single cell suspensions, obtained from rat kidneys, were cultured with various concentrations of HgCl2 for different times to examine the effects on cellular synthetic activity. Unexpectedly, the RNA synthesis of kidney cells was stimulated with low doses of HgCl2, whereas it was inhibited with higher doses. Even at a higher dose, RNA synthesis was stimulated during early incubation but was inhibited during longer incubations. Thus, the effect of mercury showed a biphasic pattern both in dose-response and time-response relationships. Moreover, once the cells were exposed to HgCl2 for a certain period, RNA syntehsis was irreversibly inhibited. Since RNA synthesis was inhibited earlier than DNA or a protein synthesis, the RNA synthesizing system appeared most susceptible. Without HgCl2, by the time DNA synthesis reached its maximum, protein and RNA synthesis had already declined. In contrast, RNA synthesis of HgCl2-treated cells remained at its maximal level and showed no decline when DNA synthesis reached its peak."} {"id": "PMID:1271751", "title": "Characteristics of epithelial cella cultured from feline lung.", "content": "Cell cultures were initiated by trypsinization of lung tissues obtained from 55-day-old fetuses of Felis catus. After a period of cultivation, the cells were cloned and several clones with an epithelial morphology were established. On electron microscopy, at least four of the clones contained intracytoplasmic lamellar inclusion bodies typical in appearance to those observed in type II alveolar cell in situ. These clones should be invaluable for the study of the biosynthesis of long surfactant.", "contents": "Characteristics of epithelial cella cultured from feline lung. Cell cultures were initiated by trypsinization of lung tissues obtained from 55-day-old fetuses of Felis catus. After a period of cultivation, the cells were cloned and several clones with an epithelial morphology were established. On electron microscopy, at least four of the clones contained intracytoplasmic lamellar inclusion bodies typical in appearance to those observed in type II alveolar cell in situ. These clones should be invaluable for the study of the biosynthesis of long surfactant."} {"id": "PMID:1271752", "title": "Disseminated intravascular coagulation induced by Liquoid in the rat. II. Effect of heparin on hematologic and complement abnormalities and renal lesions studied by light, fluorescence, and electron microscopy.", "content": "A single intravenous injection (12.5 mg.) of Liquoid (polyanethol sulfonate) was given to anticoagulated (heparinized) rats. Fibrinogen concentrations, platelet counts, total serum complement (CH50),C3 protein, and terminal components (C3 to C9) were measured. Histopathology was assessed by light, fluorescence, and electron microscopy. Heparin given before Liquoid remarkably diminished the seferity of the histologic lesions, with good correlation among light, fluorescence, and electron microscopy. Levels of clotting factors, CH50, C3 and C3 to C9, however, were not statistically different in the heparinized rats injected with Liquoid from those of animals receiving Liquoid alone. Actually C3 protein concentration was lower in the anticoagulated (Liquoid-heparin) rats. It is postulated that under the present experimental conditions, heparin did not antagonize the procoagulant and precipitating or complement-activating Liquoid effects. The attenuated histopathology observed was perhaps the result of either local or systemic, as yet undefined, heparin effects other than anticoagulation.", "contents": "Disseminated intravascular coagulation induced by Liquoid in the rat. II. Effect of heparin on hematologic and complement abnormalities and renal lesions studied by light, fluorescence, and electron microscopy. A single intravenous injection (12.5 mg.) of Liquoid (polyanethol sulfonate) was given to anticoagulated (heparinized) rats. Fibrinogen concentrations, platelet counts, total serum complement (CH50),C3 protein, and terminal components (C3 to C9) were measured. Histopathology was assessed by light, fluorescence, and electron microscopy. Heparin given before Liquoid remarkably diminished the seferity of the histologic lesions, with good correlation among light, fluorescence, and electron microscopy. Levels of clotting factors, CH50, C3 and C3 to C9, however, were not statistically different in the heparinized rats injected with Liquoid from those of animals receiving Liquoid alone. Actually C3 protein concentration was lower in the anticoagulated (Liquoid-heparin) rats. It is postulated that under the present experimental conditions, heparin did not antagonize the procoagulant and precipitating or complement-activating Liquoid effects. The attenuated histopathology observed was perhaps the result of either local or systemic, as yet undefined, heparin effects other than anticoagulation."} {"id": "PMID:1271753", "title": "Effects of indomethacin on renomedullary interstitial cells.", "content": "The effects of indomethacin, an inhibitor of prostaglandin synthesis, on rat renomedullary interstitial cells were studied. Indomethacin, 5 mg. per kg. intravenously in divided doses over 48 hours, resulted in reduced granularity of interstitial cells (5.56+/-1.37 versus 9.85+/-1.07 granules per cell, (p is less than 0.001) and, at the same time, inhibited the incorporation of 14C-arachidonate into renomedullary phospholipids (715 + 11 versus 1299 + 42 c.pm.per mug. of lipid orthophosphate; p is less than 0.001) 14C-arachidonate incorporation into cortical phospholipids was not affected by indomethacin. There was a close correlation between individual granule counts and 14C-arachidonate incorporation into medullary phospholipids for both control (r=0.85) and indomethacin-treated animals (r=0.9). Radioactivity in the cytosol fraction was depressed by indomethacin reflecting inhibition of prostaglandin synthesis; cytosol radioactivity correlated closely with individual granule count (r=0.81) in the indomethacin-treated but not in the control rats. Indomethacin given as a single dose 4 hours prior to sacrifice resulted in a significant depression of 14C-arachidonate incorporation but did not affect granularity of interstitial cells. The results suggest that granularity of renomedullary interstitial cells reflects the activity of prostaglandin synthesis and the rate of prostaglandin precursor delivery from microsomal phospholipids.", "contents": "Effects of indomethacin on renomedullary interstitial cells. The effects of indomethacin, an inhibitor of prostaglandin synthesis, on rat renomedullary interstitial cells were studied. Indomethacin, 5 mg. per kg. intravenously in divided doses over 48 hours, resulted in reduced granularity of interstitial cells (5.56+/-1.37 versus 9.85+/-1.07 granules per cell, (p is less than 0.001) and, at the same time, inhibited the incorporation of 14C-arachidonate into renomedullary phospholipids (715 + 11 versus 1299 + 42 c.pm.per mug. of lipid orthophosphate; p is less than 0.001) 14C-arachidonate incorporation into cortical phospholipids was not affected by indomethacin. There was a close correlation between individual granule counts and 14C-arachidonate incorporation into medullary phospholipids for both control (r=0.85) and indomethacin-treated animals (r=0.9). Radioactivity in the cytosol fraction was depressed by indomethacin reflecting inhibition of prostaglandin synthesis; cytosol radioactivity correlated closely with individual granule count (r=0.81) in the indomethacin-treated but not in the control rats. Indomethacin given as a single dose 4 hours prior to sacrifice resulted in a significant depression of 14C-arachidonate incorporation but did not affect granularity of interstitial cells. The results suggest that granularity of renomedullary interstitial cells reflects the activity of prostaglandin synthesis and the rate of prostaglandin precursor delivery from microsomal phospholipids."} {"id": "PMID:1271754", "title": "Initiation of lung cell proliferation by trypsin.", "content": "The ability of trypsin to initiate DNA synthesis in alveolar epithelial cells of mice was tested by introducing solutions containing trypsin into the lung. The concentrations tested ranged from 0.01 to 1.0 mg. per ml., the site of action was identified by adding colloidal carbon as a tracer, and chromosomal DNA synthesis was detected by autoradiography on the basis of strong nuclear incorporation of tritiated thymidine. In the above concentration range trypsin did not cause cell necrosis, general fragmentation of cell processes, or loss of mechanical contact at epithelial cell junctions. Edema and focal acute inflammation were apparent at concentrations of trypsin above 0.1 mg. per ml. In the alveolar epithelium maximal labeling was seen 2 days after treatment with 0.5 mg. per ml. of trypsin. At this time electron microscope autoradiography covering two \"S\" periods showed that one-third of the type II cells were labeled. No labeled type I cells were seen. Trypsin at levels less than 0.1 mg. per ml. did not increase the frequency of labeled type II cells above that of the saline-colloidal ink solution alone. Mesothelial cells lining the lung were stimulated by trypsin (0.5 mg.) given intrapleurally. The frequency of mesothelial cell labeling peaked at 2 days with a labeling index for a single tritiated thymidine pulse of 18 per cent. Neither alveolar type II cells nor mesothelial cells showed increased labeling when trypsin inactivated by diisopropyl fluorophosphate was used.", "contents": "Initiation of lung cell proliferation by trypsin. The ability of trypsin to initiate DNA synthesis in alveolar epithelial cells of mice was tested by introducing solutions containing trypsin into the lung. The concentrations tested ranged from 0.01 to 1.0 mg. per ml., the site of action was identified by adding colloidal carbon as a tracer, and chromosomal DNA synthesis was detected by autoradiography on the basis of strong nuclear incorporation of tritiated thymidine. In the above concentration range trypsin did not cause cell necrosis, general fragmentation of cell processes, or loss of mechanical contact at epithelial cell junctions. Edema and focal acute inflammation were apparent at concentrations of trypsin above 0.1 mg. per ml. In the alveolar epithelium maximal labeling was seen 2 days after treatment with 0.5 mg. per ml. of trypsin. At this time electron microscope autoradiography covering two \"S\" periods showed that one-third of the type II cells were labeled. No labeled type I cells were seen. Trypsin at levels less than 0.1 mg. per ml. did not increase the frequency of labeled type II cells above that of the saline-colloidal ink solution alone. Mesothelial cells lining the lung were stimulated by trypsin (0.5 mg.) given intrapleurally. The frequency of mesothelial cell labeling peaked at 2 days with a labeling index for a single tritiated thymidine pulse of 18 per cent. Neither alveolar type II cells nor mesothelial cells showed increased labeling when trypsin inactivated by diisopropyl fluorophosphate was used."} {"id": "PMID:1271777", "title": "The use of auditory masking to estimate automatization of correct articulatory production.", "content": "In order to estimate automatization of correct articulatory production in 71 elementary school children about to be dismissed from training, auditory masking was used during administration of the Deep Test of Articulation. White noise was presented binaurally at 86 dB SPL. The children's articulation was tested under three conditions: Condition I without masking, Condition II with masking, and Condition III without masking three to four months after Condition II testing. Children's performances on Conditions I and II were compared with their performances during Condition III. Results demonstrated that performance on the Deep Test during auditory masking as a criterion for dismissal would have resulted in children being correctly dismissed from therapy more of the time (94%) than the traditional (nonmasked) administration of the test (77%). In addition, use of experimental administration of the test would have resulted in 6% of the children being incorrectly dismissed from therapy while traditional administration would have resulted in 23% of the children being incorrectly dismissed. Clinical importance and implications for further investigation are discussed.", "contents": "The use of auditory masking to estimate automatization of correct articulatory production. In order to estimate automatization of correct articulatory production in 71 elementary school children about to be dismissed from training, auditory masking was used during administration of the Deep Test of Articulation. White noise was presented binaurally at 86 dB SPL. The children's articulation was tested under three conditions: Condition I without masking, Condition II with masking, and Condition III without masking three to four months after Condition II testing. Children's performances on Conditions I and II were compared with their performances during Condition III. Results demonstrated that performance on the Deep Test during auditory masking as a criterion for dismissal would have resulted in children being correctly dismissed from therapy more of the time (94%) than the traditional (nonmasked) administration of the test (77%). In addition, use of experimental administration of the test would have resulted in 6% of the children being incorrectly dismissed from therapy while traditional administration would have resulted in 23% of the children being incorrectly dismissed. Clinical importance and implications for further investigation are discussed."} {"id": "PMID:1271778", "title": "Developmental assessment of Spanish grammar.", "content": "The Developmental Assessment of Spanish Grammar (DASG) provides a language analysis procedure for Spanish-speaking children similar to the Developmental Sentence Scoring (DSS) procedure in English. The DASG is not an attempted translation of the DSS but was developed independently, taking into consideration the present knowledge of Spanish language acquisition. The purpose of the DASG is to evaluate the language of children with deficient grammatical skills in Spanish and to serve as a model for structuring Spanish language therapy. Proposed syntactic hierarchies for the following six grammatical categories are presented: indefinite pronouns and noun modifiers, personal pronouns, primary verbs, secondary verbs, conjunctions, and interrogative words. Weighted scores are assigned to groups of structures within the hierarchies and are used to score Spanish sentences children use spontaneously in conversation with an adult. The DASG was standardized on 128 Spanish-speaking children between the ages of 3.0 and 6.11 years. Norms and reliability measures are presented.", "contents": "Developmental assessment of Spanish grammar. The Developmental Assessment of Spanish Grammar (DASG) provides a language analysis procedure for Spanish-speaking children similar to the Developmental Sentence Scoring (DSS) procedure in English. The DASG is not an attempted translation of the DSS but was developed independently, taking into consideration the present knowledge of Spanish language acquisition. The purpose of the DASG is to evaluate the language of children with deficient grammatical skills in Spanish and to serve as a model for structuring Spanish language therapy. Proposed syntactic hierarchies for the following six grammatical categories are presented: indefinite pronouns and noun modifiers, personal pronouns, primary verbs, secondary verbs, conjunctions, and interrogative words. Weighted scores are assigned to groups of structures within the hierarchies and are used to score Spanish sentences children use spontaneously in conversation with an adult. The DASG was standardized on 128 Spanish-speaking children between the ages of 3.0 and 6.11 years. Norms and reliability measures are presented."} {"id": "PMID:1271779", "title": "Tongue thrust: a point of view.", "content": "The purpose of the present paper is to present evidence to support the following hypotheses: (1) there is a relationship between tongue thrust and malocclusion, and it is probably a reciprocal one; (2) tongue thrust may yield spontaneously to non-thrusting patterns; (3) if tongue thrust does not yield spontaneously to nonthrusting patterns, some form of treatment should be considered; (4) if myofunctional therapy is the treatment of choice, its timing with respect to patient age, developmental factors, and orthodontic treatment should be an individual matter. The need for more definitive research is described. In order for such research to be meaningful, a standard definition of tongue thrust is required. Such a definition is proposed.", "contents": "Tongue thrust: a point of view. The purpose of the present paper is to present evidence to support the following hypotheses: (1) there is a relationship between tongue thrust and malocclusion, and it is probably a reciprocal one; (2) tongue thrust may yield spontaneously to non-thrusting patterns; (3) if tongue thrust does not yield spontaneously to nonthrusting patterns, some form of treatment should be considered; (4) if myofunctional therapy is the treatment of choice, its timing with respect to patient age, developmental factors, and orthodontic treatment should be an individual matter. The need for more definitive research is described. In order for such research to be meaningful, a standard definition of tongue thrust is required. Such a definition is proposed."} {"id": "PMID:1271780", "title": "The phonological systems of deaf children.", "content": "Samples of a group of deaf children's spontaneous speech were used to derive phonological rules. The predictive value of some of the rules was assessed by asking another group of deaf children to lip-read and read nonsense words. The results indicated that the phonological systems of profoundly deaf children are partially rule-governed. There was also some evidence which suggested that lipreading was a major input to the deaf children's phonological systems.", "contents": "The phonological systems of deaf children. Samples of a group of deaf children's spontaneous speech were used to derive phonological rules. The predictive value of some of the rules was assessed by asking another group of deaf children to lip-read and read nonsense words. The results indicated that the phonological systems of profoundly deaf children are partially rule-governed. There was also some evidence which suggested that lipreading was a major input to the deaf children's phonological systems."} {"id": "PMID:1271781", "title": "The modification of multiple articulation errors based on distinctive feature theory.", "content": "The effectiveness of articulation remediation procedures based on distinctive feature theory was evaluated through the administration of an articulation program designed for this purpose. Two preschool children with multiple phoneme errors which could be described by a distinctive feature analysis were the subjects. Both children substituted stop phonemes for most continuant phonemes. Each child was individually administered the distinctive feature program which is described in full. Data are presented which indicate the adequacy of the treatment program, the acquisition of correct articulation of the two directly treated target phonemes, and the concurrent improvement of five other nontreated error phonemes. Such across-phoneme generalization was predicted by distinctive feature theory. Certain modifications in the treatment program are suggested and theoretical/empirical questions regarding articulation remediation from a distinctive features viewpoint are discussed.", "contents": "The modification of multiple articulation errors based on distinctive feature theory. The effectiveness of articulation remediation procedures based on distinctive feature theory was evaluated through the administration of an articulation program designed for this purpose. Two preschool children with multiple phoneme errors which could be described by a distinctive feature analysis were the subjects. Both children substituted stop phonemes for most continuant phonemes. Each child was individually administered the distinctive feature program which is described in full. Data are presented which indicate the adequacy of the treatment program, the acquisition of correct articulation of the two directly treated target phonemes, and the concurrent improvement of five other nontreated error phonemes. Such across-phoneme generalization was predicted by distinctive feature theory. Certain modifications in the treatment program are suggested and theoretical/empirical questions regarding articulation remediation from a distinctive features viewpoint are discussed."} {"id": "PMID:1271782", "title": "Children's perception of time-compressed speech on two measures of speech discrimination.", "content": "Time-compressed versions of the WIPI and PB-K 50 speech discrimination measures were presented at two sensation levels to 60 children divided into three age-groups of 20 each. Results showed that average intelligibility scores increased as a function of increasing age and sensation level and decreased with increasing amounts of time compression. The PB-K 50 measure was found to be more difficult than the WIPI for each age-group under each condition of time compression and sensation level. The several factors under study were found to interact. The results are discussed relative to open- versus closed-message set response tasks and the implications for audiological diagnoses of children with central auditory processing problems.", "contents": "Children's perception of time-compressed speech on two measures of speech discrimination. Time-compressed versions of the WIPI and PB-K 50 speech discrimination measures were presented at two sensation levels to 60 children divided into three age-groups of 20 each. Results showed that average intelligibility scores increased as a function of increasing age and sensation level and decreased with increasing amounts of time compression. The PB-K 50 measure was found to be more difficult than the WIPI for each age-group under each condition of time compression and sensation level. The several factors under study were found to interact. The results are discussed relative to open- versus closed-message set response tasks and the implications for audiological diagnoses of children with central auditory processing problems."} {"id": "PMID:1271783", "title": "Acquisition of lipreading in a deaf multihandicapped child.", "content": "Operant techniques were used to develop lipreading in a nine-year-old deaf boy who had failed to respond appropriately to previous speechreading training. Remediation was initiated with two experiments: the first entailed a reversal and the second a multiple baseline. A component analysis revealed that both tokens and social reinforcers presented simultaneously or separately were effective in shaping lipreading. In addition, the child learned to lip-read either voiced or nonvoiced names of objects.", "contents": "Acquisition of lipreading in a deaf multihandicapped child. Operant techniques were used to develop lipreading in a nine-year-old deaf boy who had failed to respond appropriately to previous speechreading training. Remediation was initiated with two experiments: the first entailed a reversal and the second a multiple baseline. A component analysis revealed that both tokens and social reinforcers presented simultaneously or separately were effective in shaping lipreading. In addition, the child learned to lip-read either voiced or nonvoiced names of objects."} {"id": "PMID:1271784", "title": "Acquisition of esophageal speech subsequent to learning pharyngeal speech: an unusual case study.", "content": "Laryngectomees who are delayed in obtaining alaryngeal voice therapy may develop pharyngeal voice, an undesirable type of alaryngeal voice. Pharyngeal voice is usually self-developed; however, it may also be acquired in the clinical setting when the patient is being taught to inject air for esophageal sound production. This report describes the principal findings involving a laryngectomee who had developed and used pharyngeal speech as his primary method of communication for two years prior to enrollment in alaryngeal voice therapy. A clinical technique that was found to be successful in altering the pharyngeal voice to esophageal voice is reported. Findings pertaining to the overall intelligibility as well as vocal fundamental frequency of the two different types of alaryngeal speech are included.", "contents": "Acquisition of esophageal speech subsequent to learning pharyngeal speech: an unusual case study. Laryngectomees who are delayed in obtaining alaryngeal voice therapy may develop pharyngeal voice, an undesirable type of alaryngeal voice. Pharyngeal voice is usually self-developed; however, it may also be acquired in the clinical setting when the patient is being taught to inject air for esophageal sound production. This report describes the principal findings involving a laryngectomee who had developed and used pharyngeal speech as his primary method of communication for two years prior to enrollment in alaryngeal voice therapy. A clinical technique that was found to be successful in altering the pharyngeal voice to esophageal voice is reported. Findings pertaining to the overall intelligibility as well as vocal fundamental frequency of the two different types of alaryngeal speech are included."} {"id": "PMID:1271785", "title": "Spouses' understanding of the communication disabilities of aphasic patients.", "content": "The language skills of 11 aphasic patients were assessed through the use of the PICA. Spuses's understanding of the aphasic partner's language deficits was measured by rating the aphasic spouse on the Functional Communication Profile. Results indicate that spouses of aphasic patients view the patient's communication to be less impaired than it actually is. Implications for the counseling role of the speech pathologist in language therapy are discussed.", "contents": "Spouses' understanding of the communication disabilities of aphasic patients. The language skills of 11 aphasic patients were assessed through the use of the PICA. Spuses's understanding of the aphasic partner's language deficits was measured by rating the aphasic spouse on the Functional Communication Profile. Results indicate that spouses of aphasic patients view the patient's communication to be less impaired than it actually is. Implications for the counseling role of the speech pathologist in language therapy are discussed."} {"id": "PMID:1271786", "title": "Critical bandwidth and sensitivity prediction in the acoustic stapedial reflex.", "content": "Critical bandwidth measurements and sensitivity prediction from the acoustic reflex (SPAR) test results were obtained on 20 normal-hearing and two groups of 10 hearing-impaired subjects each representing mild-to-moderate and severe hearing loss. Results of critical bandwidth measurements indicated that for center frequencies of 1000 and 2000 Hz the critical bandwidth was significantly greater for the hearing-impaired subjects. A statistical analysis of the differences in critical bandwidth between those predicted by the SPAR test to have a mild-to-moderate hearing loss and those subjects for whom the test predicted severe hearing loss indicated no differences in critical bandwidth at 2000 Hz. A significant difference was found at 1000 Hz but in the wrong direction. Analysis of the relationship between predicted slope of hearing loss and critical bandwidth also failed to show significance. Although the data for hearing-impaired subjects fail to support the rationale for the SPAR test, the results for the entire research sample offer substantial support. Further, the ability of the test to predict categorically degree of hearing loss was also strongly supported.", "contents": "Critical bandwidth and sensitivity prediction in the acoustic stapedial reflex. Critical bandwidth measurements and sensitivity prediction from the acoustic reflex (SPAR) test results were obtained on 20 normal-hearing and two groups of 10 hearing-impaired subjects each representing mild-to-moderate and severe hearing loss. Results of critical bandwidth measurements indicated that for center frequencies of 1000 and 2000 Hz the critical bandwidth was significantly greater for the hearing-impaired subjects. A statistical analysis of the differences in critical bandwidth between those predicted by the SPAR test to have a mild-to-moderate hearing loss and those subjects for whom the test predicted severe hearing loss indicated no differences in critical bandwidth at 2000 Hz. A significant difference was found at 1000 Hz but in the wrong direction. Analysis of the relationship between predicted slope of hearing loss and critical bandwidth also failed to show significance. Although the data for hearing-impaired subjects fail to support the rationale for the SPAR test, the results for the entire research sample offer substantial support. Further, the ability of the test to predict categorically degree of hearing loss was also strongly supported."} {"id": "PMID:1271787", "title": "Therapeutic approaches to apraxia.", "content": "Although identifying descriptions of apraxia are numerous in recent literature, few articles present guidelines for apraxia therapy. In this paper, several therapeutic techniques for apraxia are introduced and discussed. Sequencing of speech sounds is recognized as the apraxic patient's most characteristic problem. Rapid repetition of consonant plus /a/, build-up of speech sounds into syllables, and word attack by phone and syllable are all recommended for the purpose of improving sequencing. Facilitation techniques are discussed for the acquisition of articulatory postures. Case histories are presented to illustrate the therapy approach.", "contents": "Therapeutic approaches to apraxia. Although identifying descriptions of apraxia are numerous in recent literature, few articles present guidelines for apraxia therapy. In this paper, several therapeutic techniques for apraxia are introduced and discussed. Sequencing of speech sounds is recognized as the apraxic patient's most characteristic problem. Rapid repetition of consonant plus /a/, build-up of speech sounds into syllables, and word attack by phone and syllable are all recommended for the purpose of improving sequencing. Facilitation techniques are discussed for the acquisition of articulatory postures. Case histories are presented to illustrate the therapy approach."} {"id": "PMID:1271791", "title": "Effects of sentence context on recognition of words through lipreading by deaf children.", "content": "Twenty monosyllabic nouns (10 animate, 10 inanimate) were presented in isolation and in three different positions in sentences to 15 profoundly deaf children to determine the effect of context on word intelligibility through lipreading. Isolated words were more intelligible (80%) than were words in sentences (46%). Animate nouns were more intelligible (70%) than inanimate nouns (33%) when used in initial position (as subjects) in sentences. Teacher ratings of children's \"general lipreading ability\" were correlated more highly with their recognition of words in the test sentences (r = 0.93) than with their recognition of words presented in isolation (r = 0.53). The results indicate that teachers of deaf children could enhance the intelligibility of important words by isolating them from sentences. The results also suggest that some speech-perception difficulties of deaf children could be diagnosed through lipreading tests which are scored on the basis of correctness of \"key words\" in sentences.", "contents": "Effects of sentence context on recognition of words through lipreading by deaf children. Twenty monosyllabic nouns (10 animate, 10 inanimate) were presented in isolation and in three different positions in sentences to 15 profoundly deaf children to determine the effect of context on word intelligibility through lipreading. Isolated words were more intelligible (80%) than were words in sentences (46%). Animate nouns were more intelligible (70%) than inanimate nouns (33%) when used in initial position (as subjects) in sentences. Teacher ratings of children's \"general lipreading ability\" were correlated more highly with their recognition of words in the test sentences (r = 0.93) than with their recognition of words presented in isolation (r = 0.53). The results indicate that teachers of deaf children could enhance the intelligibility of important words by isolating them from sentences. The results also suggest that some speech-perception difficulties of deaf children could be diagnosed through lipreading tests which are scored on the basis of correctness of \"key words\" in sentences."} {"id": "PMID:1271792", "title": "Pronominalization in the language of deaf students.", "content": "Four hundred and eighty deaf students (age 10 to 18 years) and 60 hearing children (age eight to 10 years) were required to complete a stimulus sentence by selecting the appropriate pronoun from a list provided. The results indicated that subject and object case pronouns were easier than possessive adjectives, which were in turn easier than possessive pronouns and reflexives. Correct use of relative pronouns was the most difficult for both deaf and hearing subjects. Generalizations about the acquisition of the pronoun system must be limited, as it appeared that pronouns are mastered on a pronoun-by-pronoun basis rather than by categories (person, number, case) for both the deaf and hearing subjects.", "contents": "Pronominalization in the language of deaf students. Four hundred and eighty deaf students (age 10 to 18 years) and 60 hearing children (age eight to 10 years) were required to complete a stimulus sentence by selecting the appropriate pronoun from a list provided. The results indicated that subject and object case pronouns were easier than possessive adjectives, which were in turn easier than possessive pronouns and reflexives. Correct use of relative pronouns was the most difficult for both deaf and hearing subjects. Generalizations about the acquisition of the pronoun system must be limited, as it appeared that pronouns are mastered on a pronoun-by-pronoun basis rather than by categories (person, number, case) for both the deaf and hearing subjects."} {"id": "PMID:1271793", "title": "The effects of word length and visual complexity on verbal reaction times.", "content": "Thirty adult subjects learned to associate nonsense names varying in word length with nonsense visual stimuli varying in visual complexity. Simple reaction times (SRTs), visual duration thresholds (VDTs), matching response latencies (MRLs), and naming response latencies (NRLs) were then obtained from these subjects. The data indicate that SRTs, VDTs, and NRLs are significantly related to word length and that VDTs and NRLs are significantly related to visual complexity. There is also a tendency for MRLs to increase with increases in word length, particularly for \"no\" responses. However, the effects of word length on VDTs, MRLs, and NRLs may be confounded with the number of trials needed to learn the paired associates or with the number of overlearning trials. The data are consistent with an interpretation that motor planning or some form of implicit speech process may be a part of the total time required for the naming response.", "contents": "The effects of word length and visual complexity on verbal reaction times. Thirty adult subjects learned to associate nonsense names varying in word length with nonsense visual stimuli varying in visual complexity. Simple reaction times (SRTs), visual duration thresholds (VDTs), matching response latencies (MRLs), and naming response latencies (NRLs) were then obtained from these subjects. The data indicate that SRTs, VDTs, and NRLs are significantly related to word length and that VDTs and NRLs are significantly related to visual complexity. There is also a tendency for MRLs to increase with increases in word length, particularly for \"no\" responses. However, the effects of word length on VDTs, MRLs, and NRLs may be confounded with the number of trials needed to learn the paired associates or with the number of overlearning trials. The data are consistent with an interpretation that motor planning or some form of implicit speech process may be a part of the total time required for the naming response."} {"id": "PMID:1271794", "title": "Binaural masking effects in bone-conducted noise.", "content": "When pure tones are masked by bone-conducted noise presented at the midline of the forehead, it is possible that binaural unmasking may occur due to the interaural phase relations of the noise. To study this possibility, the amount of masking produced in bone-conducted noise, in correlated air-conducted noise, and in monaural noise was determined using narrow bands of noise centered at 240, 500, 910, and 1900 Hz as markers and a block up-down two-interval forced choice procedure. The subjects were four women under 30 years of age with 10 dB HTL or better (ANSI, 1969) for the frequencies tested. The amount of unmasking (the masking-level difference) was determined by subtracting the masking levels obtained under each noise condition at each frequency from those obtained in the comparable monaural noise-monaural signal condition. Levels of binaural unmasking obtained in correlated air-conducted noise agreed with those in previously reported experiments. Comparable binaural unmasking effects were demonstrated for midline presentation of bone-conducted noise. Some clinical implications of the findings are discussed.", "contents": "Binaural masking effects in bone-conducted noise. When pure tones are masked by bone-conducted noise presented at the midline of the forehead, it is possible that binaural unmasking may occur due to the interaural phase relations of the noise. To study this possibility, the amount of masking produced in bone-conducted noise, in correlated air-conducted noise, and in monaural noise was determined using narrow bands of noise centered at 240, 500, 910, and 1900 Hz as markers and a block up-down two-interval forced choice procedure. The subjects were four women under 30 years of age with 10 dB HTL or better (ANSI, 1969) for the frequencies tested. The amount of unmasking (the masking-level difference) was determined by subtracting the masking levels obtained under each noise condition at each frequency from those obtained in the comparable monaural noise-monaural signal condition. Levels of binaural unmasking obtained in correlated air-conducted noise agreed with those in previously reported experiments. Comparable binaural unmasking effects were demonstrated for midline presentation of bone-conducted noise. Some clinical implications of the findings are discussed."} {"id": "PMID:1271795", "title": "A comparison of the contributions of two voice quality characteristics to the perception of maleness and femaleness in the voice.", "content": "Comparisons were made between the contributions of the fundamental frequency (F0) on one hand, and vocal tract resonances on the other, to a perception of maleness and femaleness in the adult voice. In the first of two experiments, the F0 of natural voice was found to be very highly correlated with the degree of maleness and femaleness in the voice. The vocal tract resonances were less highly correlated and it is apparent that in the presence of the natural laryngeal tone, these perceptions are based on the frequency of the F0. In the second experiment, a tone produced by a laryngeal vibrator was substituted for the normal glottal tone at simulated F0's representing both males (120 Hz) and females (240 Hz). When listeners were asked to identify the sex of the speakers some inconsistently with the findings of the first experiment was seen. The female F0 was a weak indicator of female voice quality when combined with male vocal tract resonance although the male F0 retained the perceptual prominence seen in the first experiment. This finding may be indicative of some basic difference in the normal glottal characteristics of males and females.", "contents": "A comparison of the contributions of two voice quality characteristics to the perception of maleness and femaleness in the voice. Comparisons were made between the contributions of the fundamental frequency (F0) on one hand, and vocal tract resonances on the other, to a perception of maleness and femaleness in the adult voice. In the first of two experiments, the F0 of natural voice was found to be very highly correlated with the degree of maleness and femaleness in the voice. The vocal tract resonances were less highly correlated and it is apparent that in the presence of the natural laryngeal tone, these perceptions are based on the frequency of the F0. In the second experiment, a tone produced by a laryngeal vibrator was substituted for the normal glottal tone at simulated F0's representing both males (120 Hz) and females (240 Hz). When listeners were asked to identify the sex of the speakers some inconsistently with the findings of the first experiment was seen. The female F0 was a weak indicator of female voice quality when combined with male vocal tract resonance although the male F0 retained the perceptual prominence seen in the first experiment. This finding may be indicative of some basic difference in the normal glottal characteristics of males and females."} {"id": "PMID:1271796", "title": "Bone conduction thresholds for normal listeners in force and acceleration units.", "content": "In a previous article we reported on the standardization of normal hearing for bone conduction. All of our findings were reported in force units. Because many international users of this information express such findings in units of acceleration, we have, at the Editor's request, converted our force units into acceleration units to increase the scope of our results and to enhance their comparison with other investigations. This note presents data which may be useful to organization concerned with the development of standards for normal hearing by bone conduction.", "contents": "Bone conduction thresholds for normal listeners in force and acceleration units. In a previous article we reported on the standardization of normal hearing for bone conduction. All of our findings were reported in force units. Because many international users of this information express such findings in units of acceleration, we have, at the Editor's request, converted our force units into acceleration units to increase the scope of our results and to enhance their comparison with other investigations. This note presents data which may be useful to organization concerned with the development of standards for normal hearing by bone conduction."} {"id": "PMID:1271798", "title": "Motor impairment following blockade of the infraorbital nerve: implications for the use of anesthetization techniques in speech research.", "content": "Infraorbital nerve blocks were performed bilaterally in three subjects as a partial test of the hypothesis that some portion of the motor innervation to the facial muscles is provided in the trigeminal nerve. To ascertain the influence of this anesthetic procedure, the magnitude and rate of upper lip displacement (for speech and nonspeech tasks), the magnitude and rate of upper lip depression force, and diadochokinetic rate were transduced and recorded, both pre- and postanesthesia. All measures, along with bilateral muscle action potentials from orbicularis oris superior obtained for all force and displacement tasks, were reduced in magnitude as a function of the anesthetic condition. These findings, along with results from previous speech anesthetic studies, were interpreted to suggest that anesthesia of the infraorbital nerve produces measurable, if not substantial motor weakness in the supraoral musculature. The implications for previous studies, where anesthesia techniques have been employed, are discussed.", "contents": "Motor impairment following blockade of the infraorbital nerve: implications for the use of anesthetization techniques in speech research. Infraorbital nerve blocks were performed bilaterally in three subjects as a partial test of the hypothesis that some portion of the motor innervation to the facial muscles is provided in the trigeminal nerve. To ascertain the influence of this anesthetic procedure, the magnitude and rate of upper lip displacement (for speech and nonspeech tasks), the magnitude and rate of upper lip depression force, and diadochokinetic rate were transduced and recorded, both pre- and postanesthesia. All measures, along with bilateral muscle action potentials from orbicularis oris superior obtained for all force and displacement tasks, were reduced in magnitude as a function of the anesthetic condition. These findings, along with results from previous speech anesthetic studies, were interpreted to suggest that anesthesia of the infraorbital nerve produces measurable, if not substantial motor weakness in the supraoral musculature. The implications for previous studies, where anesthesia techniques have been employed, are discussed."} {"id": "PMID:1271799", "title": "Instructed rehearsal strategies' influence on deaf memory processing.", "content": "Congenitally deaf subjects were compared with normal-hearing subjects on short-term retention accuracy and correct response latency. The subjects paced themselves through serial lists of consonant letters six- or seven-items long. Presentation of each list was followed by a position-probe test requiring the subjects to specify where in the list a particular letter had appeared. The subjects were first observed while generating their own input strategies (free strategy). In subsequent sessions they adopted instructed rehearsal strategies involving primary and secondary memory components. Overall, the normal-hearing subjects were more accurate and responded faster than the deaf subjects. Instructing rehearsal strategies resulted in immediate gains on these measures for both groups. For both measures the deaf subjects became at least as proficient as the normal-hearing subjects had been under free strategy. The patterns of correct response latencies for the groups revealed strikingly different comparisons for primary and secondary memory. Following strategy instruction, latencies for the terminal list items never differed for the two groups, indicating that primary memory in the deaf is fully intact. However, the deaf responded slower on the first items of the list, indicating secondary memory deficiencies.", "contents": "Instructed rehearsal strategies' influence on deaf memory processing. Congenitally deaf subjects were compared with normal-hearing subjects on short-term retention accuracy and correct response latency. The subjects paced themselves through serial lists of consonant letters six- or seven-items long. Presentation of each list was followed by a position-probe test requiring the subjects to specify where in the list a particular letter had appeared. The subjects were first observed while generating their own input strategies (free strategy). In subsequent sessions they adopted instructed rehearsal strategies involving primary and secondary memory components. Overall, the normal-hearing subjects were more accurate and responded faster than the deaf subjects. Instructing rehearsal strategies resulted in immediate gains on these measures for both groups. For both measures the deaf subjects became at least as proficient as the normal-hearing subjects had been under free strategy. The patterns of correct response latencies for the groups revealed strikingly different comparisons for primary and secondary memory. Following strategy instruction, latencies for the terminal list items never differed for the two groups, indicating that primary memory in the deaf is fully intact. However, the deaf responded slower on the first items of the list, indicating secondary memory deficiencies."} {"id": "PMID:1271800", "title": "Use of low-pass noise in word-recognition testing.", "content": "This study attempted to determine whether word-recognition scores obtained in noise were more sensitive to the presence of a hearing loss than recognition scores obtained in quiet. Subjects with normal hearing, high-frequency cochlear hearing loss, and flat cochlear hearing loss were tested in quiet and in the presence of a 500-Hz low-pass noise. Two signal-to-noise conditions were employed, -4 dB and -12 dB. Words were presented at 40dB SL in one experiment and at 96 dB SPL for normal-hearing subjects in a second experiment. The results indicated that, while the word-recognition scores of groups were similar in quiet, the more negative the signal-to-noise ratio, the greater the separation of group scores, with hearing-impaired subjects having poorer recognition scores than normal-hearing subjects. When the speech and noise were presented at high SPLs, however, the normal-hearing subjects had poorer word recognition than those with flat cochlear losses. The results are interpreted as indicating greater spread of masking in normal-hearing than hearing-impaired subjects at high sound pressure levels.", "contents": "Use of low-pass noise in word-recognition testing. This study attempted to determine whether word-recognition scores obtained in noise were more sensitive to the presence of a hearing loss than recognition scores obtained in quiet. Subjects with normal hearing, high-frequency cochlear hearing loss, and flat cochlear hearing loss were tested in quiet and in the presence of a 500-Hz low-pass noise. Two signal-to-noise conditions were employed, -4 dB and -12 dB. Words were presented at 40dB SL in one experiment and at 96 dB SPL for normal-hearing subjects in a second experiment. The results indicated that, while the word-recognition scores of groups were similar in quiet, the more negative the signal-to-noise ratio, the greater the separation of group scores, with hearing-impaired subjects having poorer recognition scores than normal-hearing subjects. When the speech and noise were presented at high SPLs, however, the normal-hearing subjects had poorer word recognition than those with flat cochlear losses. The results are interpreted as indicating greater spread of masking in normal-hearing than hearing-impaired subjects at high sound pressure levels."} {"id": "PMID:1271801", "title": "Tutorial: application of regression analysis concepts to retrospective research in speech pathology.", "content": "The underlying logic of retrospective research in speech pathology is examined critically. This research model focuses on differences among discrete groups. Regression analysis concepts are suggested as a tool to evaluate the practical or theoretical importance of statistically significant differences obtained in retrospective research. This type of analysis focuses on the degree to which a criterion measure can be predicted from knowledge of group classification, rather than on differences among means.", "contents": "Tutorial: application of regression analysis concepts to retrospective research in speech pathology. The underlying logic of retrospective research in speech pathology is examined critically. This research model focuses on differences among discrete groups. Regression analysis concepts are suggested as a tool to evaluate the practical or theoretical importance of statistically significant differences obtained in retrospective research. This type of analysis focuses on the degree to which a criterion measure can be predicted from knowledge of group classification, rather than on differences among means."} {"id": "PMID:1271802", "title": "Time-intensity trading functions for selected pure tones.", "content": "A substantial number of investigations have examined the ability of the auditory system to trade time for intensity on a lateralization task. Most of these investigations, however, have employed clicks and noise bursts as stimuli with interaural disparities between onset times. Consequently, there is a lack of quantitative data for time-intensity trades where pure tones that had identical onset times but disparate phase were employed as signals. For this reason we employed sinusoids ranging from 200 to 2000 Hz and determined the extent to which the intensity of one signal must be decreased to achieve a midline image when interaural phase disparities of 0 degrees to 360 degrees were imposed between the binaural signals in 30 degree increments. The time-intensity trading functions yielded in this experiment demonstrate that (1) not unexpectedly, the largest time-intensity trades were accomplished for the lower frequencies; (2) the maximum time-intensity trade for each frequency occurred at interaural phase disparities of 90 degrees and 270 degrees; and (3) when the low-frequency tones were 180 degrees out of phase, essentially the same intraaural intensity relationship was required to achieve midline as was needed for the 0 degree interaural phase condition.", "contents": "Time-intensity trading functions for selected pure tones. A substantial number of investigations have examined the ability of the auditory system to trade time for intensity on a lateralization task. Most of these investigations, however, have employed clicks and noise bursts as stimuli with interaural disparities between onset times. Consequently, there is a lack of quantitative data for time-intensity trades where pure tones that had identical onset times but disparate phase were employed as signals. For this reason we employed sinusoids ranging from 200 to 2000 Hz and determined the extent to which the intensity of one signal must be decreased to achieve a midline image when interaural phase disparities of 0 degrees to 360 degrees were imposed between the binaural signals in 30 degree increments. The time-intensity trading functions yielded in this experiment demonstrate that (1) not unexpectedly, the largest time-intensity trades were accomplished for the lower frequencies; (2) the maximum time-intensity trade for each frequency occurred at interaural phase disparities of 90 degrees and 270 degrees; and (3) when the low-frequency tones were 180 degrees out of phase, essentially the same intraaural intensity relationship was required to achieve midline as was needed for the 0 degree interaural phase condition."} {"id": "PMID:1271803", "title": "INDSCAL analysis of perceptual judgments for 24 consonants via visual, tactile, and visual-tactile inputs.", "content": "Twenty-four normal-hearing subjects received CV stimuli of uni- and bisensory inputs through the visual (speechreading), tactile (touch), and visual-tactile (speechreading and touch) modalities. Stimuli were presented via either a videotape monitor or a tactile vibrator or both. The purposes were to investigate the contribution of the tactile modality in uni- and bisensory conditions, and to analyze consonantal substitution errors to find perceptual features utilized by the subjects in their decision-making processes. The subjects' consonantal perceptions were phonetically transcribed and submitted to INDSCAL analysis which yielded mainly a four-dimensional solution. The interpretations of these dimensions were primarily closed bilabial, easy to see/hard to see, voiced/voiceless, and front/back place. Additional features were retrieved, but occurred less consistently.", "contents": "INDSCAL analysis of perceptual judgments for 24 consonants via visual, tactile, and visual-tactile inputs. Twenty-four normal-hearing subjects received CV stimuli of uni- and bisensory inputs through the visual (speechreading), tactile (touch), and visual-tactile (speechreading and touch) modalities. Stimuli were presented via either a videotape monitor or a tactile vibrator or both. The purposes were to investigate the contribution of the tactile modality in uni- and bisensory conditions, and to analyze consonantal substitution errors to find perceptual features utilized by the subjects in their decision-making processes. The subjects' consonantal perceptions were phonetically transcribed and submitted to INDSCAL analysis which yielded mainly a four-dimensional solution. The interpretations of these dimensions were primarily closed bilabial, easy to see/hard to see, voiced/voiceless, and front/back place. Additional features were retrieved, but occurred less consistently."} {"id": "PMID:1271804", "title": "Influence of encoding and acoustic similarity on the ear advantage and lag effect in dichotic listening.", "content": "Experiments with simultaneous and time lag dichotic listening conditions were used to test two hypotheses concerning the right ear advantage and lag effect in dichotic listening. One hypothesis is based on the similarity of acoustic spectra, and the other is based on a categorization of speech sounds as being either encoded or not encoded. Natural vowels and consonant-vowel syllables were used to obtain seven different types of speech stimuli: stop vowel syllables, fricative vowel syllables, stop burst noise, fricative noise, stop vowel transitions, fricative vowel transitions and steady state vowels. The presentation conditions were monaural, simultaneous dichotic, and dichotic with interaural time delays of 15, 30, 60, and 90 msec. With monaural presentations, all stimuli were identifiable above chance levels. For the simultaneous dichotic condition, significant right ear advantages occurred for stop vowel syllables, fricative vowel syllables, stop burst noise, and steady state vowels. For the time lag conditions, stop vowel syllables, stop bursts, and fricative noise produced consistent lag effects, but steady state vowels produced consistent lead effects. In general, the results gave stronger support to the hypothesis of acoustic similarity than to the encoding hypothesis in that stop burst noise produced both a right ear advantage and a lag effect whereas consonant-vowel transitions produced neither a right ear advantage nor a lag effect.", "contents": "Influence of encoding and acoustic similarity on the ear advantage and lag effect in dichotic listening. Experiments with simultaneous and time lag dichotic listening conditions were used to test two hypotheses concerning the right ear advantage and lag effect in dichotic listening. One hypothesis is based on the similarity of acoustic spectra, and the other is based on a categorization of speech sounds as being either encoded or not encoded. Natural vowels and consonant-vowel syllables were used to obtain seven different types of speech stimuli: stop vowel syllables, fricative vowel syllables, stop burst noise, fricative noise, stop vowel transitions, fricative vowel transitions and steady state vowels. The presentation conditions were monaural, simultaneous dichotic, and dichotic with interaural time delays of 15, 30, 60, and 90 msec. With monaural presentations, all stimuli were identifiable above chance levels. For the simultaneous dichotic condition, significant right ear advantages occurred for stop vowel syllables, fricative vowel syllables, stop burst noise, and steady state vowels. For the time lag conditions, stop vowel syllables, stop bursts, and fricative noise produced consistent lag effects, but steady state vowels produced consistent lead effects. In general, the results gave stronger support to the hypothesis of acoustic similarity than to the encoding hypothesis in that stop burst noise produced both a right ear advantage and a lag effect whereas consonant-vowel transitions produced neither a right ear advantage nor a lag effect."} {"id": "PMID:1271805", "title": "Development of the voicing contrast: a comparison of voice onset time in stop preception and production.", "content": "The acoustic cue voice onset time (VOT) was used to study development of the voicing contrast in 10 two-year-old children, 10 six-year-old children, and 20 adults. Thirty utterances of the words bees, peas, bear, pear, dime, time, goat, and coat were elicited from each subject, VOT measured, and individual production distributions for labial, apical, and velar stops plotted. Significant age-related differences were shown for mean VOT, mean lead time for voiced stops, range of the same words that were examined in the production portion of the investigation were obtained for these subjects from their judgments of synthetic speech stimuli. The relationship between identification and production was examined by assessing the degree of correspondence between the perception and production VOT values. Results of this analysis showed a developmental pattern of change primarily for the voiceless stops in the form of increased correspondence between perceptual identification categories and production VOT values. Three stages for acquisition of the voicing contrast related to VOT are indicated.", "contents": "Development of the voicing contrast: a comparison of voice onset time in stop preception and production. The acoustic cue voice onset time (VOT) was used to study development of the voicing contrast in 10 two-year-old children, 10 six-year-old children, and 20 adults. Thirty utterances of the words bees, peas, bear, pear, dime, time, goat, and coat were elicited from each subject, VOT measured, and individual production distributions for labial, apical, and velar stops plotted. Significant age-related differences were shown for mean VOT, mean lead time for voiced stops, range of the same words that were examined in the production portion of the investigation were obtained for these subjects from their judgments of synthetic speech stimuli. The relationship between identification and production was examined by assessing the degree of correspondence between the perception and production VOT values. Results of this analysis showed a developmental pattern of change primarily for the voiceless stops in the form of increased correspondence between perceptual identification categories and production VOT values. Three stages for acquisition of the voicing contrast related to VOT are indicated."} {"id": "PMID:1271833", "title": "Columnar cell-lined esophagus: assessment of etiology and treatment. A 22 year experience.", "content": "Among 1,000 patients with hiatal hernias were 45 who had biopsy-proved columnar-lined esophagus (CLE). Twenty-one were male and 24 female, with bimodal age ranges peaking at zero to 10 and 48 to 80 years. Of the first decade patients, all boys, 2 were brothers. While 44 had dysphagia, one third also had iron-deficiency anemia. All had x-ray-proved sliding hiatal hernias, with esophageal stricturing at the squamous cell-columnar cell interface. In 43 cases this area was 35 cm. or less from the upper jaw. The epithelial histology showed simple, tubular, mucus-secreting glands (45 cases), goblet cells (7 cases), no goblet cells (38 cases), and gastric-type epithelium with parietal cells (19 cases). In 2 cases CLE was rising up the esophagus from 35 to 30 cm. in 3 years and from 40 to 23 cm. in 10 years. No stricture became neoplastic. Clinical evidence supports the view that CLE has a double etiology: It is congenital in children but acquired, akin to \"intestinalization of the stomach,\" in adults with sliding hiatal hernias; in the latter instance, CLE occurs as an alternative end-point to reflux esophagitis. Treatments and long-term results are discussed. All patients had initial stricture dilatation with biopsy. In 17 this was the sole treatment. In 16 cases a later transthoracic herniorrhaphy was performed to reduce the hiatal hernia and prevent further stricturing. Fifteen patients had transmural strictures. For this group, our experience with Roux-Y esophagogastrostomy and esophagojejunogastrostomy, with stricture excision, and also with mere bypass of the stricture is stated. For the young, after stricture excision, eosophagojejunogastrostomy with pyloroplasty, performed in the second decade, is favored. In the elderly, especially after unsuccessful hiatal herniorrhaphy, eosophagojejunogastrostomy with stricture bypass proved satisfactory 3 years after the operation.", "contents": "Columnar cell-lined esophagus: assessment of etiology and treatment. A 22 year experience. Among 1,000 patients with hiatal hernias were 45 who had biopsy-proved columnar-lined esophagus (CLE). Twenty-one were male and 24 female, with bimodal age ranges peaking at zero to 10 and 48 to 80 years. Of the first decade patients, all boys, 2 were brothers. While 44 had dysphagia, one third also had iron-deficiency anemia. All had x-ray-proved sliding hiatal hernias, with esophageal stricturing at the squamous cell-columnar cell interface. In 43 cases this area was 35 cm. or less from the upper jaw. The epithelial histology showed simple, tubular, mucus-secreting glands (45 cases), goblet cells (7 cases), no goblet cells (38 cases), and gastric-type epithelium with parietal cells (19 cases). In 2 cases CLE was rising up the esophagus from 35 to 30 cm. in 3 years and from 40 to 23 cm. in 10 years. No stricture became neoplastic. Clinical evidence supports the view that CLE has a double etiology: It is congenital in children but acquired, akin to \"intestinalization of the stomach,\" in adults with sliding hiatal hernias; in the latter instance, CLE occurs as an alternative end-point to reflux esophagitis. Treatments and long-term results are discussed. All patients had initial stricture dilatation with biopsy. In 17 this was the sole treatment. In 16 cases a later transthoracic herniorrhaphy was performed to reduce the hiatal hernia and prevent further stricturing. Fifteen patients had transmural strictures. For this group, our experience with Roux-Y esophagogastrostomy and esophagojejunogastrostomy, with stricture excision, and also with mere bypass of the stricture is stated. For the young, after stricture excision, eosophagojejunogastrostomy with pyloroplasty, performed in the second decade, is favored. In the elderly, especially after unsuccessful hiatal herniorrhaphy, eosophagojejunogastrostomy with stricture bypass proved satisfactory 3 years after the operation."} {"id": "PMID:1271834", "title": "Congenital aneurysm of the sinus of Valsalva protruding into the left ventricle. Review of diagnosis and treatment of the unruptured aneurysm.", "content": "During a routine physical examination, a 34-year-old man, in apparent good health, had an electrocardiogram which revealed left axis deviation. Cardiac evaluation disclosed mild aortic regurgitation and left anterior fascicular block. Nine months later, the patient was admitted to the critical care unit after he had experienced cardiac arrest while jogging. Angiograms demonstrated a large unruptured aneurysm in the right coronary sinus of Valsalva protuding into the left ventricle. Echocardiographic manifestations also suggested also suggested a sinus of Valsalva aneurysm. The defect was repaired through an aortic approach. The aneurysmal sac was emptied and the neck sutured securely. Twenty-two months postoperatively, the patient continues to be asymptomatic. We anticipate that this will decrease the threat of recurrent arrhythmias..", "contents": "Congenital aneurysm of the sinus of Valsalva protruding into the left ventricle. Review of diagnosis and treatment of the unruptured aneurysm. During a routine physical examination, a 34-year-old man, in apparent good health, had an electrocardiogram which revealed left axis deviation. Cardiac evaluation disclosed mild aortic regurgitation and left anterior fascicular block. Nine months later, the patient was admitted to the critical care unit after he had experienced cardiac arrest while jogging. Angiograms demonstrated a large unruptured aneurysm in the right coronary sinus of Valsalva protuding into the left ventricle. Echocardiographic manifestations also suggested also suggested a sinus of Valsalva aneurysm. The defect was repaired through an aortic approach. The aneurysmal sac was emptied and the neck sutured securely. Twenty-two months postoperatively, the patient continues to be asymptomatic. We anticipate that this will decrease the threat of recurrent arrhythmias.."} {"id": "PMID:1271835", "title": "Systemic hypertension following myocardial revascularization. A method of treatment using epidural anesthesia.", "content": "Seven of 12 patients (58%) undergoing myocardial revascularization surgery became hypertensive in the immediate postoperative period. The hypertensive patients had significant elevations in peripheral vascular resistance (22.0 +/- 2.0 S.E. resistance units) compared to measurements in normotensive patients (15.6 +/- 1.3 S.E. resistance units) (p less than 0.05), whereas the heart rates and cardiac indices were similar. Administration of thoracic epidural anesthesia to postoperatively hypertensive patients lowered systemic arterial pressure by decreasing peripheral vascular resistance (p less than 0.005) but not affecting the pulse rate and cardiac index. The ratio diastolic pressure-time index/systemic pressure-time index (DPTI/SPTI), an indirect measurement of subendocardial oxygenation, increased from preanesthetic values of 0.80 +/- 0.08 S.E. to 1.09 +/- 0.09 S.E. (p less than 0.025) after the systemic arterial pressure was lowered in postoperatively hypertensive patients. Hypertensive episodes following myocardial revascularization procedures appear related to increased alpha-adrenergic activity, which products elevation in peripheral vascular resistance. Decreasing peripheral vascular resistance by chemical sympathectomy with thoracic epidural anesthesia lowers the systemic arterial pressure and improves the DPTI/SPTI ratio.", "contents": "Systemic hypertension following myocardial revascularization. A method of treatment using epidural anesthesia. Seven of 12 patients (58%) undergoing myocardial revascularization surgery became hypertensive in the immediate postoperative period. The hypertensive patients had significant elevations in peripheral vascular resistance (22.0 +/- 2.0 S.E. resistance units) compared to measurements in normotensive patients (15.6 +/- 1.3 S.E. resistance units) (p less than 0.05), whereas the heart rates and cardiac indices were similar. Administration of thoracic epidural anesthesia to postoperatively hypertensive patients lowered systemic arterial pressure by decreasing peripheral vascular resistance (p less than 0.005) but not affecting the pulse rate and cardiac index. The ratio diastolic pressure-time index/systemic pressure-time index (DPTI/SPTI), an indirect measurement of subendocardial oxygenation, increased from preanesthetic values of 0.80 +/- 0.08 S.E. to 1.09 +/- 0.09 S.E. (p less than 0.025) after the systemic arterial pressure was lowered in postoperatively hypertensive patients. Hypertensive episodes following myocardial revascularization procedures appear related to increased alpha-adrenergic activity, which products elevation in peripheral vascular resistance. Decreasing peripheral vascular resistance by chemical sympathectomy with thoracic epidural anesthesia lowers the systemic arterial pressure and improves the DPTI/SPTI ratio."} {"id": "PMID:1271836", "title": "Myocardial infarction complicating aortic valve replacement.", "content": "One hundred consecutive aortic valve replacements were studied. Fifteen patients had a myocardial infarction as a result of the operation, and four of the five deaths in the series stemmed from this group. In the four deaths from infarction, autopsy revealed occlusion of a main coronary artery. This was attributable to coronary perfusion in three instances. All of the 11 survivors who sustained an infarct were free of angina and left ventricular failure 6 weeks after the operation. Patients with infarcts had longer bypass times and larger aortic systolic gradients than the patients who did not have an infarct. It is suggested that an infarct can occur as the result of occlusion of a main coronary artery; this is a fatal event commonly related to trauma from the coronary perfusion cannula. Alternatively, infarction may result from regional ischemia, perhaps without vessel occlusion, and is associated with long bypass times and with large aortic valve gradients. In such cases the prognosis is good. However, myocardial infarction was the major cause of death in this series.", "contents": "Myocardial infarction complicating aortic valve replacement. One hundred consecutive aortic valve replacements were studied. Fifteen patients had a myocardial infarction as a result of the operation, and four of the five deaths in the series stemmed from this group. In the four deaths from infarction, autopsy revealed occlusion of a main coronary artery. This was attributable to coronary perfusion in three instances. All of the 11 survivors who sustained an infarct were free of angina and left ventricular failure 6 weeks after the operation. Patients with infarcts had longer bypass times and larger aortic systolic gradients than the patients who did not have an infarct. It is suggested that an infarct can occur as the result of occlusion of a main coronary artery; this is a fatal event commonly related to trauma from the coronary perfusion cannula. Alternatively, infarction may result from regional ischemia, perhaps without vessel occlusion, and is associated with long bypass times and with large aortic valve gradients. In such cases the prognosis is good. However, myocardial infarction was the major cause of death in this series."} {"id": "PMID:1271837", "title": "Cardiorespiratory failure secondary to peripheral pulmonary emboli. Survival following a combination of prolonged extracorporeal membrane oxygenator support and pulmonary embolectomy.", "content": "A 19-year-old woman developed cardiorespiratory failure from multiple, peripheral pulmonary emboli apparently developing over the preceding 3 weeks. She was not considered to be an operative candidate. However, when 3 days of intravenous heparin infusion and 30 hours of membrane oxygenator support failed to improve the pulmonary pathology, pulmonary embolectomy was performed. The membrane oxygenator support had to be continued for 34 hours following the operation before it was successfully discontinued. The patient made a complete recovery.", "contents": "Cardiorespiratory failure secondary to peripheral pulmonary emboli. Survival following a combination of prolonged extracorporeal membrane oxygenator support and pulmonary embolectomy. A 19-year-old woman developed cardiorespiratory failure from multiple, peripheral pulmonary emboli apparently developing over the preceding 3 weeks. She was not considered to be an operative candidate. However, when 3 days of intravenous heparin infusion and 30 hours of membrane oxygenator support failed to improve the pulmonary pathology, pulmonary embolectomy was performed. The membrane oxygenator support had to be continued for 34 hours following the operation before it was successfully discontinued. The patient made a complete recovery."} {"id": "PMID:1271838", "title": "CPK-MB isoenzyme: use in diagnosis of acute myocardial infarction in the early postoperative period.", "content": "The diagnosis of acute myocardial infarction (AMI) in the early postoperative period may be quite difficult in certain patients. Electrocardiograms fail to be diagnostic of AMI in as many as one third of patients with myocardial injury found at autopsy. Enzyme patterns commonly used to diagnose AMI in patients admitted to coronary care units are obscured by muscle injury, medications, cardioversion, surgical manipulation, and blood transfusion. The MB isoenzyme of creatinine phosphokinase (CPK) has been described as a specific indicator of myocardial injury. Therefore the CPK-MB isoenzyme level was evaluated as a potential aid in the diagnosis of AMI in the early postoperative period. Thirty patients undergoing cardiac surgery and 7 patients undergoing thoracic surgery not involving the heart were studied. CPK-MB isoenzyme was present in the serum in 10 of 30 patients after cardiac surgery but in none of 7 patients after thoracic surgery. The presence of CPK-MB isoenzyme was found to be a valuable adjunctive indicator in the diagnosis of AMI in the early postoperative period.", "contents": "CPK-MB isoenzyme: use in diagnosis of acute myocardial infarction in the early postoperative period. The diagnosis of acute myocardial infarction (AMI) in the early postoperative period may be quite difficult in certain patients. Electrocardiograms fail to be diagnostic of AMI in as many as one third of patients with myocardial injury found at autopsy. Enzyme patterns commonly used to diagnose AMI in patients admitted to coronary care units are obscured by muscle injury, medications, cardioversion, surgical manipulation, and blood transfusion. The MB isoenzyme of creatinine phosphokinase (CPK) has been described as a specific indicator of myocardial injury. Therefore the CPK-MB isoenzyme level was evaluated as a potential aid in the diagnosis of AMI in the early postoperative period. Thirty patients undergoing cardiac surgery and 7 patients undergoing thoracic surgery not involving the heart were studied. CPK-MB isoenzyme was present in the serum in 10 of 30 patients after cardiac surgery but in none of 7 patients after thoracic surgery. The presence of CPK-MB isoenzyme was found to be a valuable adjunctive indicator in the diagnosis of AMI in the early postoperative period."} {"id": "PMID:1271839", "title": "Arterial stenosis, pressure, and flow.", "content": "The interaction between the effects of an arterial stenosis and postocclusion hyperemia was studied in a model of the capillaron system. A capillaron is a module consisting of soft-walled permeable vessels (capillaries) in a compliant capsule. Stenosis reduced flow in accord with arterial cross-sectional area. Addition of a capillaron reduced flow to a basal level. In this basal state, autoregulation and postocclusion hyperemia could be studied. Basal flow and autoregulation give no indication of the severity of the stenosis. The magnitude of the postocclusion hyperemia varied with the arterial pressure and, inversely, with the stenotic orifice area. In the absence of arterial pressure changes, the magnitude of the postocclusion hyperemia indicates the severity of the stenosis.", "contents": "Arterial stenosis, pressure, and flow. The interaction between the effects of an arterial stenosis and postocclusion hyperemia was studied in a model of the capillaron system. A capillaron is a module consisting of soft-walled permeable vessels (capillaries) in a compliant capsule. Stenosis reduced flow in accord with arterial cross-sectional area. Addition of a capillaron reduced flow to a basal level. In this basal state, autoregulation and postocclusion hyperemia could be studied. Basal flow and autoregulation give no indication of the severity of the stenosis. The magnitude of the postocclusion hyperemia varied with the arterial pressure and, inversely, with the stenotic orifice area. In the absence of arterial pressure changes, the magnitude of the postocclusion hyperemia indicates the severity of the stenosis."} {"id": "PMID:1271840", "title": "Disc variance: a potentially lethal complication of the Beall valve prosthesis.", "content": "During 1975, 4 patients with erosion of the disc in Beall valve prostheses were seen. In one case the eroded disc was found loose in the distal aorta at postmortem examination. In 3 other cases, clinical diagnoses were made and successful reoperations performed. Because disc variance represents a potentially lethal complication, patients with disc prostheses should be examined at frequent intervals. When signs and symptoms of mechanical malfunction develop, the valve prosthesis should be replaced immediately to prevent death.", "contents": "Disc variance: a potentially lethal complication of the Beall valve prosthesis. During 1975, 4 patients with erosion of the disc in Beall valve prostheses were seen. In one case the eroded disc was found loose in the distal aorta at postmortem examination. In 3 other cases, clinical diagnoses were made and successful reoperations performed. Because disc variance represents a potentially lethal complication, patients with disc prostheses should be examined at frequent intervals. When signs and symptoms of mechanical malfunction develop, the valve prosthesis should be replaced immediately to prevent death."} {"id": "PMID:1271841", "title": "Intimal changes in arteriovenous bypass grafts. Effects of varying the angle of implantation at the proximal anastomosis and of producing stenosis in the distal runoff artery.", "content": "Autologous arteriovenous bypass grafts were constructed between external iliac arteries in 20 mongrel dogs to determine the development of intimal fibromuscular hyperplasia. Animals received grafts at 55, 90 or 120 degree angles relative to the proximal anastomosis. Five animals with 90 degree angle grafts were also subjected to 80% stenosis in the runoff artery. All grafts showed the development of a fibromuscular tunica intima. Qualitative or quantitative intimal differences were not observed among grafts placed at 90 degree angles, 90 degree angles with runoff artery stenosis, or 120 degree angles. Grafts placed at 55 degree angles relative to the proximal anastomosis developed a consistently thicker fibromuscular layer in the tunica intima when compared to the other groups. These changes which were segmental in nature, occurred in the proximal and distal grafts and over the distal anastomosis.", "contents": "Intimal changes in arteriovenous bypass grafts. Effects of varying the angle of implantation at the proximal anastomosis and of producing stenosis in the distal runoff artery. Autologous arteriovenous bypass grafts were constructed between external iliac arteries in 20 mongrel dogs to determine the development of intimal fibromuscular hyperplasia. Animals received grafts at 55, 90 or 120 degree angles relative to the proximal anastomosis. Five animals with 90 degree angle grafts were also subjected to 80% stenosis in the runoff artery. All grafts showed the development of a fibromuscular tunica intima. Qualitative or quantitative intimal differences were not observed among grafts placed at 90 degree angles, 90 degree angles with runoff artery stenosis, or 120 degree angles. Grafts placed at 55 degree angles relative to the proximal anastomosis developed a consistently thicker fibromuscular layer in the tunica intima when compared to the other groups. These changes which were segmental in nature, occurred in the proximal and distal grafts and over the distal anastomosis."} {"id": "PMID:1271842", "title": "Levels of circulating norepinephrine and epinephrine before, during, and after cardiopulmonary bypass in man.", "content": "Little information is available on the levels of circulating catecholamines during cardiac surgery. A study was undertaken to measure the serum levels of epinephrine and norepinephrine before, during, and after cardiopulmonary bypass in 16 patients. Sampling were drawn before induction, after intubation, before bypass, 2 and 8 minutes after initiation of the bypass, and 20 minutes after bypass. The findings of this study show that the initiation of cardiopulmonary bypass was associated with a significant but transient fall in mean blood pressure accompanied by an increased secretion of adrenal epinephrine and norepinephrine. The cause of the observed hypotension may be due to an initial hemodilution of the circulating catecholamines by the 2 L. pump-priming solution. The secretion of adrenal catecholamines appears to be a compensatory response to the lowered blood pressure as indicated by the rapid return of the blood pressure in the ensuing minutes. Twenty minutes after bypass, both the blood pressure and serum catecholamine levels were observed to have returned to preinduction levels.", "contents": "Levels of circulating norepinephrine and epinephrine before, during, and after cardiopulmonary bypass in man. Little information is available on the levels of circulating catecholamines during cardiac surgery. A study was undertaken to measure the serum levels of epinephrine and norepinephrine before, during, and after cardiopulmonary bypass in 16 patients. Sampling were drawn before induction, after intubation, before bypass, 2 and 8 minutes after initiation of the bypass, and 20 minutes after bypass. The findings of this study show that the initiation of cardiopulmonary bypass was associated with a significant but transient fall in mean blood pressure accompanied by an increased secretion of adrenal epinephrine and norepinephrine. The cause of the observed hypotension may be due to an initial hemodilution of the circulating catecholamines by the 2 L. pump-priming solution. The secretion of adrenal catecholamines appears to be a compensatory response to the lowered blood pressure as indicated by the rapid return of the blood pressure in the ensuing minutes. Twenty minutes after bypass, both the blood pressure and serum catecholamine levels were observed to have returned to preinduction levels."} {"id": "PMID:1271843", "title": "Severe stenosis of a viable homograft aortic valve.", "content": "A case is reported of severe stenosis developing in a homograft aortic valve which was viable at the time of implantation. Calcific stenosis should be considered a potential late complication in viable, as well as biologically inert, homograft aortic valves.", "contents": "Severe stenosis of a viable homograft aortic valve. A case is reported of severe stenosis developing in a homograft aortic valve which was viable at the time of implantation. Calcific stenosis should be considered a potential late complication in viable, as well as biologically inert, homograft aortic valves."} {"id": "PMID:1271844", "title": "Surgical management of impotence using the inflatable penile prosthesis. Experience with 36 patients.", "content": "Inflatable hydraulic penile prostheses were implanted in 36 patients who had organic impotence. Selection of patients was based on a series of guidelines that included the historical aspects of the patient's initiative, acceptance of the device by patient and partner, motivations, and psychiatric evaluation. Minor complications after implantation were not associated with the ultimate successful function of the device. Major complications were mainly mechanical in origin and readily corrected by secondary surgical procedures. The single failure in this series was associated with infection around the prosthesis, which necessitated removal of the entire device. A nearly physiologic erection was produced in 375 patients. Functional application of the implanted device was successfully achieved in 34 of 35 patients who retained their device. Patient-partner acceptance has been excellent.", "contents": "Surgical management of impotence using the inflatable penile prosthesis. Experience with 36 patients. Inflatable hydraulic penile prostheses were implanted in 36 patients who had organic impotence. Selection of patients was based on a series of guidelines that included the historical aspects of the patient's initiative, acceptance of the device by patient and partner, motivations, and psychiatric evaluation. Minor complications after implantation were not associated with the ultimate successful function of the device. Major complications were mainly mechanical in origin and readily corrected by secondary surgical procedures. The single failure in this series was associated with infection around the prosthesis, which necessitated removal of the entire device. A nearly physiologic erection was produced in 375 patients. Functional application of the implanted device was successfully achieved in 34 of 35 patients who retained their device. Patient-partner acceptance has been excellent."} {"id": "PMID:1271845", "title": "Cystometry and sphincter electromyography.", "content": "Gas cystometry combined with electronically integrated sphincter electromyography provides a rapid and effective screening technique for evaluation of patients with disorders of micturition secondary to neurologic dysfunction. The most frequent cystometric patterns are (1) detrusor hyperreflexia secondary to interruption of the cortico-regulatory tracts and (2) detrusor areflexia secondary to impairment of the segmental innervation of the detrusor muscle. To observe these patterns it is necessary to perform detrusor reflex activation procedures, including change in posture, administration of bethanechol, and urethral and rectal distention. The two prinicpal sphincter disturbances observed with electronically integrated electromyography are detrusor sphincter dyssnergia and uninhibited sphincter relaxation. The delineation of combination of abnormal cystometric and sphincter responses provides for rational selection of pharmacologic and surgical therapy.", "contents": "Cystometry and sphincter electromyography. Gas cystometry combined with electronically integrated sphincter electromyography provides a rapid and effective screening technique for evaluation of patients with disorders of micturition secondary to neurologic dysfunction. The most frequent cystometric patterns are (1) detrusor hyperreflexia secondary to interruption of the cortico-regulatory tracts and (2) detrusor areflexia secondary to impairment of the segmental innervation of the detrusor muscle. To observe these patterns it is necessary to perform detrusor reflex activation procedures, including change in posture, administration of bethanechol, and urethral and rectal distention. The two prinicpal sphincter disturbances observed with electronically integrated electromyography are detrusor sphincter dyssnergia and uninhibited sphincter relaxation. The delineation of combination of abnormal cystometric and sphincter responses provides for rational selection of pharmacologic and surgical therapy."} {"id": "PMID:1271846", "title": "Small-Carrion penile prosthesis. A new implant for management of impotence.", "content": "More than 75 patients have had excellent results using a new penile implant which consists of a silicone exterior with a silicone sponge interior. The prostheses are inserted into the corpora cavermosa; they feel and look like a normal erect penis. The prostheses are available in several lengths and two diameters, and the proper size is selected for each patient at the time of surgery. Complications have been minimal.", "contents": "Small-Carrion penile prosthesis. A new implant for management of impotence. More than 75 patients have had excellent results using a new penile implant which consists of a silicone exterior with a silicone sponge interior. The prostheses are inserted into the corpora cavermosa; they feel and look like a normal erect penis. The prostheses are available in several lengths and two diameters, and the proper size is selected for each patient at the time of surgery. Complications have been minimal."} {"id": "PMID:1271848", "title": "The implantable artificial genitourinary sphincter in the management of total urinary incontinence.", "content": "The artificial genitourinary sphincter has been implanted in 31 patients with total urinary incontinence. Minor complications associated with implantation of this device were found to be mainly mechanical in origin, resulting in malfunction of the apparatus. Postoperative mechanical malfunction, however, was found to be correctable through a variety of secondary surgical procedures. Major complications, including infection around the prosthesis, vesical neck erosion, vesical-colic fistula, and urethral erosion, were generally associated with problems of cuff placement. In nearly all cases in which major complications occurred, it was ultimately necessary to remove the prosthesis. Overall results would indicate that patients with incontinence after transurethral prostatic resection in whom the inflatable cuff was placed around the vesical neck achieved the best results (70%). In this series of 31 patients, 68% had a normally functioning sphincter with complete correction of their urinary incontinence.", "contents": "The implantable artificial genitourinary sphincter in the management of total urinary incontinence. The artificial genitourinary sphincter has been implanted in 31 patients with total urinary incontinence. Minor complications associated with implantation of this device were found to be mainly mechanical in origin, resulting in malfunction of the apparatus. Postoperative mechanical malfunction, however, was found to be correctable through a variety of secondary surgical procedures. Major complications, including infection around the prosthesis, vesical neck erosion, vesical-colic fistula, and urethral erosion, were generally associated with problems of cuff placement. In nearly all cases in which major complications occurred, it was ultimately necessary to remove the prosthesis. Overall results would indicate that patients with incontinence after transurethral prostatic resection in whom the inflatable cuff was placed around the vesical neck achieved the best results (70%). In this series of 31 patients, 68% had a normally functioning sphincter with complete correction of their urinary incontinence."} {"id": "PMID:1271849", "title": "Genitourinary prosthetics of the present and future.", "content": "Development of implantable prosthetic devices to restore genitourinary function has evolved from applying electrical stimulation techniques for bladder evaluation to adapting fluid energy transfer system for occlusion of the urethra to increase outlet resistance. These hydraulic prostheses have been implanted in several hundred patients in medical centers around the world. The principles behind the operation of this closed-loop system, an some alternative designs that simplify the implant procedure, are described here.", "contents": "Genitourinary prosthetics of the present and future. Development of implantable prosthetic devices to restore genitourinary function has evolved from applying electrical stimulation techniques for bladder evaluation to adapting fluid energy transfer system for occlusion of the urethra to increase outlet resistance. These hydraulic prostheses have been implanted in several hundred patients in medical centers around the world. The principles behind the operation of this closed-loop system, an some alternative designs that simplify the implant procedure, are described here."} {"id": "PMID:1271850", "title": "Psychogenic urinary retention in women.", "content": "There appears to be a spectrum of psychogenic urinary retention that is seen mostly in women. The degrees of psychiatric disorder and bladder disorder do not necessarily coincide. Some patients with psychogenic retention may have one acute episode temporally related to psychologic trauma. Others may present with problems related to large residual volumes such as recurrent urinary tract infection or incontinence. All patients require complete neurologic, urologic, and psychiatric evaluation. Permanent urethral catheterization is avoided if possible. Intermittent self-catheterization should be used during periods of psychotherapy and bladder training. Patients with neurogenic bladder, as determined by urodynamic studies, should be managed by bladder training and the use of pharmacologic agents when indicated.", "contents": "Psychogenic urinary retention in women. There appears to be a spectrum of psychogenic urinary retention that is seen mostly in women. The degrees of psychiatric disorder and bladder disorder do not necessarily coincide. Some patients with psychogenic retention may have one acute episode temporally related to psychologic trauma. Others may present with problems related to large residual volumes such as recurrent urinary tract infection or incontinence. All patients require complete neurologic, urologic, and psychiatric evaluation. Permanent urethral catheterization is avoided if possible. Intermittent self-catheterization should be used during periods of psychotherapy and bladder training. Patients with neurogenic bladder, as determined by urodynamic studies, should be managed by bladder training and the use of pharmacologic agents when indicated."} {"id": "PMID:1271851", "title": "Psychologic evaluation of impotent men.", "content": "Psychologic evaluations have been performed as part of the screening process on men who were candidates for surgical implantation of the inflatable penile prosthesis. Goals and methods of evaluation are discussed, with special attention to the use of interview and psychologic test results. Minnesota Multiphasic Personality Inventory profiles that suggest a psychogenic basis for impotence are presented and discussed.", "contents": "Psychologic evaluation of impotent men. Psychologic evaluations have been performed as part of the screening process on men who were candidates for surgical implantation of the inflatable penile prosthesis. Goals and methods of evaluation are discussed, with special attention to the use of interview and psychologic test results. Minnesota Multiphasic Personality Inventory profiles that suggest a psychogenic basis for impotence are presented and discussed."} {"id": "PMID:1271852", "title": "Bladder retraining. An organized program.", "content": "The management of neurogenic bladder dysfunction has been associated with a relatively high incidence of upper urinary tract infections and urosepsis. Today, the regular use of modern diagnostic tools in roentgenology and urodynamics is available. Moreover, contraindications to bladder retraining are better defined, and we have available better methods of evaluating urodynamics, superior reconstructive and corrective urologic surgery, judicious use of intermittent catheterization, and prompt detection and treatment of recurrent bacteriuria. We also know that, with an organized program of bladder retraining and follow-up, a substantial decrease in morbidity of patients with neurogenic bladder dysfunction has become possible.", "contents": "Bladder retraining. An organized program. The management of neurogenic bladder dysfunction has been associated with a relatively high incidence of upper urinary tract infections and urosepsis. Today, the regular use of modern diagnostic tools in roentgenology and urodynamics is available. Moreover, contraindications to bladder retraining are better defined, and we have available better methods of evaluating urodynamics, superior reconstructive and corrective urologic surgery, judicious use of intermittent catheterization, and prompt detection and treatment of recurrent bacteriuria. We also know that, with an organized program of bladder retraining and follow-up, a substantial decrease in morbidity of patients with neurogenic bladder dysfunction has become possible."} {"id": "PMID:1271853", "title": "Passive urethral compression with a silicone gel prosthesis for the treatment of male urinary incontinence.", "content": "Eighty-six patients who underwent implantation of the silicone gel prosthesis for post-prostatectomy incontinence are the subject of this study. The operation entails the implantation of a silicone gel prosthesis in the perineum to provide passive urethral compression. Several modifications of this operation have been implemented in the last 2 years, and analysis of our results indicates that lasting benefit can be achieved in about 70% of patients.", "contents": "Passive urethral compression with a silicone gel prosthesis for the treatment of male urinary incontinence. Eighty-six patients who underwent implantation of the silicone gel prosthesis for post-prostatectomy incontinence are the subject of this study. The operation entails the implantation of a silicone gel prosthesis in the perineum to provide passive urethral compression. Several modifications of this operation have been implemented in the last 2 years, and analysis of our results indicates that lasting benefit can be achieved in about 70% of patients."} {"id": "PMID:1271872", "title": "Differences in effect of 6-hydroxydopamine on the right and left atria from guinea-pig.", "content": "The effect of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) treatment was studied on guinea-pig atria. 6-OHDA treatment significantly reduced the positive inotropic effect of nicotine and tyramine on the left atrium, while similar treatment on the intact atria and the right atrium showed a decreased response to tyramine but not to nicotine. After 6-OHDA treatment the left atrium but not the right atrium showed supersensitivity to noradrenaline. The 6-OHDA induced reduction of catecholamine content and noradrenaline uptake was less effective on the right atrium in comparison to the left atrium and ventricles. After 6-OHDA treatment, tissue catecholamine fluorescence disappeared from all tissue layers of the left atrium but the number of specific fluorescent nerve terminals of the right atrium was only slightly decreased. These results indicate that adrenergic mechanisms of the right atrium exhibit higher resistance to sympathectomy by 6-OHDA than the left atrium.", "contents": "Differences in effect of 6-hydroxydopamine on the right and left atria from guinea-pig. The effect of chemical sympathectomy by 6-hydroxydopamine (6-OHDA) treatment was studied on guinea-pig atria. 6-OHDA treatment significantly reduced the positive inotropic effect of nicotine and tyramine on the left atrium, while similar treatment on the intact atria and the right atrium showed a decreased response to tyramine but not to nicotine. After 6-OHDA treatment the left atrium but not the right atrium showed supersensitivity to noradrenaline. The 6-OHDA induced reduction of catecholamine content and noradrenaline uptake was less effective on the right atrium in comparison to the left atrium and ventricles. After 6-OHDA treatment, tissue catecholamine fluorescence disappeared from all tissue layers of the left atrium but the number of specific fluorescent nerve terminals of the right atrium was only slightly decreased. These results indicate that adrenergic mechanisms of the right atrium exhibit higher resistance to sympathectomy by 6-OHDA than the left atrium."} {"id": "PMID:1271873", "title": "Quantitative aspects on mitochondrial monoamine oxidase in human platelets.", "content": "The number of monoamine oxidase molecules in human blood platelets has been estimated by titrating them with the irreversible monoamine oxidase inhibitor pargyline to be about 900 per thrombocyte and 200--300 per thrombocyte mitochondrion. It has also been calculated that monamine oxidase constitutes about 1/5,000 of the platelet mitochondrial outer membrane surface. Molecular turnover numbers for benzylamine and tyramine have been estimated to be about 1,470 and 720, respectively.", "contents": "Quantitative aspects on mitochondrial monoamine oxidase in human platelets. The number of monoamine oxidase molecules in human blood platelets has been estimated by titrating them with the irreversible monoamine oxidase inhibitor pargyline to be about 900 per thrombocyte and 200--300 per thrombocyte mitochondrion. It has also been calculated that monamine oxidase constitutes about 1/5,000 of the platelet mitochondrial outer membrane surface. Molecular turnover numbers for benzylamine and tyramine have been estimated to be about 1,470 and 720, respectively."} {"id": "PMID:1271874", "title": "Locus coeruleus: fibre growth regulation in oculo.", "content": "Locus coeruleus (LC) neurons from fetal and young rats survived homotransplantation to the anterior eye chamber. The outgrowth of LC fibres on sympathetically denervated host irides could be quantified precisely using Falck-Hillarp fluorescence histochemistry and [3H]metaraminol uptake. Fetal LC neurons survive better than postnatal ones and produced fibres for one month in oculo: by then )0-50% of the area of the host iris was innervated. After intraocular maturation of the CNS graft the fibre amount on the iris remained constant. Introduction of an iris graft contacting a mature LC graft immediately stimulated the LC to a complete (100%) reinnervation of the iris graft without any change of the restricted innervated area already formed on the host iris. The outgrowth of LC fibres on irides was not influenced by the presence or absence of sympathetic or parasympathetic nerves or by nerve growth factor or its antiserum. We conclude that an iris transplant offers a specific growth stimulus for the LC graft and that this stimulus is not present in the normal host iris. The nature of this stimulus is unknown but may involve the sensory denervation of the iris graft.", "contents": "Locus coeruleus: fibre growth regulation in oculo. Locus coeruleus (LC) neurons from fetal and young rats survived homotransplantation to the anterior eye chamber. The outgrowth of LC fibres on sympathetically denervated host irides could be quantified precisely using Falck-Hillarp fluorescence histochemistry and [3H]metaraminol uptake. Fetal LC neurons survive better than postnatal ones and produced fibres for one month in oculo: by then )0-50% of the area of the host iris was innervated. After intraocular maturation of the CNS graft the fibre amount on the iris remained constant. Introduction of an iris graft contacting a mature LC graft immediately stimulated the LC to a complete (100%) reinnervation of the iris graft without any change of the restricted innervated area already formed on the host iris. The outgrowth of LC fibres on irides was not influenced by the presence or absence of sympathetic or parasympathetic nerves or by nerve growth factor or its antiserum. We conclude that an iris transplant offers a specific growth stimulus for the LC graft and that this stimulus is not present in the normal host iris. The nature of this stimulus is unknown but may involve the sensory denervation of the iris graft."} {"id": "PMID:1271875", "title": "Goniomitosis in rats affected by mycoplasma or macrolides.", "content": "Infection with Mycoplasm pulmonis caused a slight increase in the incidence of chromosome breaks in goniomitotic cells of the rat testis. No differences existed between healthy and infected rats in the frequency of mitotic divisions, measured as the number of metaphases per slide. The macrolide antibiotics erythromycin and tylosin are widely used as antimycoplasmal drugs. Erythromycin was given to healthy rats intramuscularly at a concentration of 20 mg/kg, and tylosin perorally in the drinking water at a concentration of 0.1%, both for 10 days. Neither drug induced an increase in the incidence of chromosome breaks in the spermatogonia. But both these macrolides caused a definite reduction in the therapy of cell division. With erythromycin, this effect had disappeared 18 days after the end of treatment.", "contents": "Goniomitosis in rats affected by mycoplasma or macrolides. Infection with Mycoplasm pulmonis caused a slight increase in the incidence of chromosome breaks in goniomitotic cells of the rat testis. No differences existed between healthy and infected rats in the frequency of mitotic divisions, measured as the number of metaphases per slide. The macrolide antibiotics erythromycin and tylosin are widely used as antimycoplasmal drugs. Erythromycin was given to healthy rats intramuscularly at a concentration of 20 mg/kg, and tylosin perorally in the drinking water at a concentration of 0.1%, both for 10 days. Neither drug induced an increase in the incidence of chromosome breaks in the spermatogonia. But both these macrolides caused a definite reduction in the therapy of cell division. With erythromycin, this effect had disappeared 18 days after the end of treatment."} {"id": "PMID:1271876", "title": "Goniomitosis in rats subjected to ethanol.", "content": "Prolonged compulsory consumption of ethyl alcohol does not increase the incidence of chromosomal abnormalities in the spermatogonial cells of the rat. This was the result of an experiment in which rats given a nutritionally adequate diet received 10% (v/v) ethyl alcohol as their only supply of liquid for 70 days.", "contents": "Goniomitosis in rats subjected to ethanol. Prolonged compulsory consumption of ethyl alcohol does not increase the incidence of chromosomal abnormalities in the spermatogonial cells of the rat. This was the result of an experiment in which rats given a nutritionally adequate diet received 10% (v/v) ethyl alcohol as their only supply of liquid for 70 days."} {"id": "PMID:1271877", "title": "The survival of Toxoplasma gondii trophozoites in changes in osmotic pressure.", "content": "It has generally been assumed that the trophozoites of Toxoplasma gondii cannot survive long outside the body and they cannot resist even small changes in osmotic pressure, and that toxoplasmosis is transmitted by transplacental infection, cysts and oocysts. In an attempt to demonstrate that trophozoites can resist changes in osmotic pressure, some were preserved in ascitic fluid made hypertonic with 1%, 2%, 5%, and 10% salt excess of sodium chloride and in ascitic fluid made hypotonic by mixing it in the ratio 3 : 7, 1 : 9 and 1 : 49 with distilled water. The trophozoites remained infectious in 1% salt excess for 29 days, in 2% for 15 days, in 5% for 5 days and in 10% salt excess for 2 days and in ascitic fluid diluted 3 : 7 with distilled water for 15 days and in ascitic fluid diluted 1 : 9 with distilled water for 3 days. We suggest that trophozoites, being resistant to changes in osmotic pressure, may survive outside the body long enough to transmit the disease.", "contents": "The survival of Toxoplasma gondii trophozoites in changes in osmotic pressure. It has generally been assumed that the trophozoites of Toxoplasma gondii cannot survive long outside the body and they cannot resist even small changes in osmotic pressure, and that toxoplasmosis is transmitted by transplacental infection, cysts and oocysts. In an attempt to demonstrate that trophozoites can resist changes in osmotic pressure, some were preserved in ascitic fluid made hypertonic with 1%, 2%, 5%, and 10% salt excess of sodium chloride and in ascitic fluid made hypotonic by mixing it in the ratio 3 : 7, 1 : 9 and 1 : 49 with distilled water. The trophozoites remained infectious in 1% salt excess for 29 days, in 2% for 15 days, in 5% for 5 days and in 10% salt excess for 2 days and in ascitic fluid diluted 3 : 7 with distilled water for 15 days and in ascitic fluid diluted 1 : 9 with distilled water for 3 days. We suggest that trophozoites, being resistant to changes in osmotic pressure, may survive outside the body long enough to transmit the disease."} {"id": "PMID:1271878", "title": "Individual variation in mushroom poisoning induced in the male rate by Cortinarius speciosissimus.", "content": "The renal toxicity of a homogenate of Cortinarius speciosissimus was studied in male rats after oral administration of 100, 500 and 1,000 mg of dried mushroom/kg body weight. Great individual variation in response to the mushroom toxins was observed. At high doses (500 mg/kg and 1,000 mg/kg) the percentage of treated animals which showed renal damage did not increase in proportion of the dose. 20--30% of the rats appeared to be resistant to the toxins of C. speciosissimus, even after large doses. However, in those animals which were affected the severity of renal damage was dose-dependent. The great individual variation in the response to C. speciosissimus toxins could be explained by genetic variation.", "contents": "Individual variation in mushroom poisoning induced in the male rate by Cortinarius speciosissimus. The renal toxicity of a homogenate of Cortinarius speciosissimus was studied in male rats after oral administration of 100, 500 and 1,000 mg of dried mushroom/kg body weight. Great individual variation in response to the mushroom toxins was observed. At high doses (500 mg/kg and 1,000 mg/kg) the percentage of treated animals which showed renal damage did not increase in proportion of the dose. 20--30% of the rats appeared to be resistant to the toxins of C. speciosissimus, even after large doses. However, in those animals which were affected the severity of renal damage was dose-dependent. The great individual variation in the response to C. speciosissimus toxins could be explained by genetic variation."} {"id": "PMID:1271879", "title": "Continuity of medical care: conceptualization and measurement.", "content": "Continuity of medical care is conceived as the extent to which services are received as part of a coordinated and uninterrupted succession of events consistent with the medical care needs of patients. Two operational measures are proposed, based on the Gini and CON indices of concentration. Examples of their application are provided using the 1970 CHAS-NORC national study of health services utilization. The validity of the proposed measures is assessed in a preliminary fashion, and some commonly held assumptions about the relationship between access, quality, and continuity of care are challenged. Advantages of the proposed measures include their ability to summarize a distribution, the availability of data for construction, the relative ease of computation and interpretation, and their sensitivity to organizational changes in the delivery of health services.", "contents": "Continuity of medical care: conceptualization and measurement. Continuity of medical care is conceived as the extent to which services are received as part of a coordinated and uninterrupted succession of events consistent with the medical care needs of patients. Two operational measures are proposed, based on the Gini and CON indices of concentration. Examples of their application are provided using the 1970 CHAS-NORC national study of health services utilization. The validity of the proposed measures is assessed in a preliminary fashion, and some commonly held assumptions about the relationship between access, quality, and continuity of care are challenged. Advantages of the proposed measures include their ability to summarize a distribution, the availability of data for construction, the relative ease of computation and interpretation, and their sensitivity to organizational changes in the delivery of health services."} {"id": "PMID:1271880", "title": "The effects of social characteristics on the utilization of preventive medical services in contrasting health care programs.", "content": "This study, based on household interviews of employed individuals and their families, examines the effects of type of health insurance program and various sociodemographic factors on patterns of use of preventive medical services. A major concern of the paper is to explore the issue of whether participants in prepaid group practice use preventive services more than those in alternative insurance plans. The results show little differences in utilization among subscribers in a prepaid group plan as compared with a comparable sample of those in Blue Cross-Surgical Care plans. However, children in the prepaid plan, as compared with those in the more traditional Blue Cross plans, were more likely to receive general checkups and tuberculin skin tests in the prior year. Contrary to expectations, we found that in the employed population studied, black adults reported more preventive medical utilization than whites, and the black-white difference was the strongest single sociodemographic correlate of adult utilization of preventive care. The reporting of general checkups for children was highest among single-child families, for children under five years of age, and for those with better educated parents.", "contents": "The effects of social characteristics on the utilization of preventive medical services in contrasting health care programs. This study, based on household interviews of employed individuals and their families, examines the effects of type of health insurance program and various sociodemographic factors on patterns of use of preventive medical services. A major concern of the paper is to explore the issue of whether participants in prepaid group practice use preventive services more than those in alternative insurance plans. The results show little differences in utilization among subscribers in a prepaid group plan as compared with a comparable sample of those in Blue Cross-Surgical Care plans. However, children in the prepaid plan, as compared with those in the more traditional Blue Cross plans, were more likely to receive general checkups and tuberculin skin tests in the prior year. Contrary to expectations, we found that in the employed population studied, black adults reported more preventive medical utilization than whites, and the black-white difference was the strongest single sociodemographic correlate of adult utilization of preventive care. The reporting of general checkups for children was highest among single-child families, for children under five years of age, and for those with better educated parents."} {"id": "PMID:1271881", "title": "Socioeconomic and need determinants of ambulatory care use: path analysis of the 1970 Health Interview Survey data.", "content": "Path analysis is applied to a subsample of the 1970 National Health Interview Survey data to identify the direct and indirect effects of major socioeconomic determinants of ambulatory care utilization. The recursive model of ten equations is predicated on the notion that the dominant determinant is need, measured as activity limitation caused by chronic conditions and restricted activity days. Age, sex, income, education, and other variables are seen both as direct determinants and as acting through their effects on morbidity. The results demonstrate a complex set of relationships among the variables not identifiable in less complex analyses. Both income and education are shown to have pervasive effects. The measure of chronic disability is shown not only to affect utilization directly but to have an even larger indirect effect through its association with increased incidence of acute conditions.", "contents": "Socioeconomic and need determinants of ambulatory care use: path analysis of the 1970 Health Interview Survey data. Path analysis is applied to a subsample of the 1970 National Health Interview Survey data to identify the direct and indirect effects of major socioeconomic determinants of ambulatory care utilization. The recursive model of ten equations is predicated on the notion that the dominant determinant is need, measured as activity limitation caused by chronic conditions and restricted activity days. Age, sex, income, education, and other variables are seen both as direct determinants and as acting through their effects on morbidity. The results demonstrate a complex set of relationships among the variables not identifiable in less complex analyses. Both income and education are shown to have pervasive effects. The measure of chronic disability is shown not only to affect utilization directly but to have an even larger indirect effect through its association with increased incidence of acute conditions."} {"id": "PMID:1271882", "title": "Psychological and social factors as predictors of medical behavior.", "content": "Response to illness was studied in a group of 251 low-income mothers who brought a child to a pediatric clinic for treatment. Measures of illness and use of medical care services for the child constituted the dependent variables; social characteristics of the mother, and her health beliefs and attitudes served as the independent variables. The information was collected by means of personal interviews. A major determinant of seeking care was the presence of symptoms in the child. Age, number of children, beliefs about illness threat, and about the benefits of medical care also related to obtaining care. A measure of the scope of services used, however, was unrelated to illness, but positively related to both education and the mother's evaluation of physicians. With illness taken into account, situational barriers plus beliefs concerning illness threat and the efficacy of care become more important predictors of utilization of care. The beliefs are related to the mother's experience, education, and life situation. It was concluded that health beliefs interact with situational demands and constraints in relation to actions taken in the face of health threats.", "contents": "Psychological and social factors as predictors of medical behavior. Response to illness was studied in a group of 251 low-income mothers who brought a child to a pediatric clinic for treatment. Measures of illness and use of medical care services for the child constituted the dependent variables; social characteristics of the mother, and her health beliefs and attitudes served as the independent variables. The information was collected by means of personal interviews. A major determinant of seeking care was the presence of symptoms in the child. Age, number of children, beliefs about illness threat, and about the benefits of medical care also related to obtaining care. A measure of the scope of services used, however, was unrelated to illness, but positively related to both education and the mother's evaluation of physicians. With illness taken into account, situational barriers plus beliefs concerning illness threat and the efficacy of care become more important predictors of utilization of care. The beliefs are related to the mother's experience, education, and life situation. It was concluded that health beliefs interact with situational demands and constraints in relation to actions taken in the face of health threats."} {"id": "PMID:1271883", "title": "The effects of an experimental prepaid group practice on medical care utilization and cost.", "content": "Rates of utilization and costs of medical care by a study group in a prepaid group practice, the Medical Care Group of Washington University (MCG), were compared prospectively over a three-year period with those of a demonstrably similar control group cared for by fee-for-service private physicians. MCG enrollees used twice the ambulatory services control enrollees did (p=less than 0.01), but used 23 per cent fewer hospital days (p=less than 0.01). Cost per diagnostic and therapeutic visit was similar for both groups; MCG preventive visits cost more. Increased numbers of MCG services provided led to increased ambulatory care costs for MCG over controls. Hospital utilization savings did not compensate for these increased costs. Thus prepayment in an organized setting did change hospital and ambulatory care utilization but did not reduce medical care costs. Other changes in medical care besides those which result from a different organization of medical care are discussed which might make control of medical care costs more likely.", "contents": "The effects of an experimental prepaid group practice on medical care utilization and cost. Rates of utilization and costs of medical care by a study group in a prepaid group practice, the Medical Care Group of Washington University (MCG), were compared prospectively over a three-year period with those of a demonstrably similar control group cared for by fee-for-service private physicians. MCG enrollees used twice the ambulatory services control enrollees did (p=less than 0.01), but used 23 per cent fewer hospital days (p=less than 0.01). Cost per diagnostic and therapeutic visit was similar for both groups; MCG preventive visits cost more. Increased numbers of MCG services provided led to increased ambulatory care costs for MCG over controls. Hospital utilization savings did not compensate for these increased costs. Thus prepayment in an organized setting did change hospital and ambulatory care utilization but did not reduce medical care costs. Other changes in medical care besides those which result from a different organization of medical care are discussed which might make control of medical care costs more likely."} {"id": "PMID:1271884", "title": "The International Classification of Health Problems for Primary Care.", "content": "Health problems of patients seen in the ambulatory setting are different from those encountered in the hospital, and the particular classification of diseases used should reflect these differences. The International Classification of Health Problems in Primary Care (ICHPPC) was designed for use by primary care physicians. It was tested in multiple sites in several countries for one year and has been approved by the World Organization of National Colleges and Academies of Family Medicine-General Practice and other groups concerned with the classification of diseases. The ICHPPC permits classification of the most important part of an ambulatory data see. Data generated by using this classification facilitate outreach to a practice population, construction of diagnostic profiles of health care providers, design of curriculum and health services research.", "contents": "The International Classification of Health Problems for Primary Care. Health problems of patients seen in the ambulatory setting are different from those encountered in the hospital, and the particular classification of diseases used should reflect these differences. The International Classification of Health Problems in Primary Care (ICHPPC) was designed for use by primary care physicians. It was tested in multiple sites in several countries for one year and has been approved by the World Organization of National Colleges and Academies of Family Medicine-General Practice and other groups concerned with the classification of diseases. The ICHPPC permits classification of the most important part of an ambulatory data see. Data generated by using this classification facilitate outreach to a practice population, construction of diagnostic profiles of health care providers, design of curriculum and health services research."} {"id": "PMID:1271886", "title": "Immunotherapy for accessible tumors utilizing delayed hypersensitivity reactions and separated components of the immune system.", "content": "Courses of repeated delayed hypersensitivity challenge reactions at the sites of tumors have been shown to eradicate malignant and premalignant epidermal neoplasms. Local immunotherapy produces therapeutic responses in malignant and premalignant lesions before they are clinically detectable. This leads to a reduced incidence and prevention of tumors. Immunotherapeutic approaches are effective in controlling the early stages of mycosis fungoides and may aid in the management of the cutaneous manifestations in the late stages of the disease. Immunotherapeutic methods induce regressions of soft tissue lesions of a number of multifocal or metastatic malignant diseases with or without concurrent chemotherapy. Immunotherapeutic effects on tumors are similar with primary and recall antigens. Separated components of the cell-mediated immune system induce regressions of tumors following intralesional or perilesional administration, indicating common factors in host defenses against malignant diseases.", "contents": "Immunotherapy for accessible tumors utilizing delayed hypersensitivity reactions and separated components of the immune system. Courses of repeated delayed hypersensitivity challenge reactions at the sites of tumors have been shown to eradicate malignant and premalignant epidermal neoplasms. Local immunotherapy produces therapeutic responses in malignant and premalignant lesions before they are clinically detectable. This leads to a reduced incidence and prevention of tumors. Immunotherapeutic approaches are effective in controlling the early stages of mycosis fungoides and may aid in the management of the cutaneous manifestations in the late stages of the disease. Immunotherapeutic methods induce regressions of soft tissue lesions of a number of multifocal or metastatic malignant diseases with or without concurrent chemotherapy. Immunotherapeutic effects on tumors are similar with primary and recall antigens. Separated components of the cell-mediated immune system induce regressions of tumors following intralesional or perilesional administration, indicating common factors in host defenses against malignant diseases."} {"id": "PMID:1271887", "title": "Intralesional immunotherapy of melanoma with BCG.", "content": "Treatment of recurrent cutaneous melanoma nodules with BCG is an effective and relatively nonmorbid method for eliminating these tumor nodules. Injected nodules can be made to disappear about 90 per cent of the time and in about 20 per cent of patients non-injected nodules in the same drainage area may also regress. Subcutaneous melanoma nodules are far more resistant to melanoma injection. Although cutaneous nodules can be made to regress there is no evidence that a systemic effect against disseminated melanoma exists and no responses of distant visceral disease have been seen following intralesional therapy of cutaneous nodules. The regression of cutaneous nodules following BCG injection appears to be an immunologic phenomenon and is related to the immunocompetence of the patient. The molecular mechanisms of this tumor regression are unknown and are the subject of intensive study. Several new approaches such as the use of BCG for the treatment of poor prognosis primary malignant melanomas, as well as the use of nonviable, nonbacteriologic agents for intralesional treatment are under investigation.", "contents": "Intralesional immunotherapy of melanoma with BCG. Treatment of recurrent cutaneous melanoma nodules with BCG is an effective and relatively nonmorbid method for eliminating these tumor nodules. Injected nodules can be made to disappear about 90 per cent of the time and in about 20 per cent of patients non-injected nodules in the same drainage area may also regress. Subcutaneous melanoma nodules are far more resistant to melanoma injection. Although cutaneous nodules can be made to regress there is no evidence that a systemic effect against disseminated melanoma exists and no responses of distant visceral disease have been seen following intralesional therapy of cutaneous nodules. The regression of cutaneous nodules following BCG injection appears to be an immunologic phenomenon and is related to the immunocompetence of the patient. The molecular mechanisms of this tumor regression are unknown and are the subject of intensive study. Several new approaches such as the use of BCG for the treatment of poor prognosis primary malignant melanomas, as well as the use of nonviable, nonbacteriologic agents for intralesional treatment are under investigation."} {"id": "PMID:1271888", "title": "BCG immunotherapy as a systemic adjunct to surgery in malignant melanoma.", "content": "Results of our study suggest that BCG systemic adjuvant immunotherapy may be effective for improving both the recurrence and survival rates in patients with regional metastases from malignant melanoma. BCG is more effective in patients with small amounts of subclinical disease. It is apparent from results of clinical trials that many of the principles derived from the study of animal tumor systems are applicable to human cancer in that immunotherapy is most effective for a small residual number of tumor cells. BCG treatment fulfills many of the ideal criteria for adjuvant treatment following surgery. It is relatively nontoxic; it is effective for disseminated melanoma; it has systemic activity in the adjuvant treatment of subclinical metastases. Hwever, until clinical trials are complete, this treatment as adjuvant therapy must be considered investigational.", "contents": "BCG immunotherapy as a systemic adjunct to surgery in malignant melanoma. Results of our study suggest that BCG systemic adjuvant immunotherapy may be effective for improving both the recurrence and survival rates in patients with regional metastases from malignant melanoma. BCG is more effective in patients with small amounts of subclinical disease. It is apparent from results of clinical trials that many of the principles derived from the study of animal tumor systems are applicable to human cancer in that immunotherapy is most effective for a small residual number of tumor cells. BCG treatment fulfills many of the ideal criteria for adjuvant treatment following surgery. It is relatively nontoxic; it is effective for disseminated melanoma; it has systemic activity in the adjuvant treatment of subclinical metastases. Hwever, until clinical trials are complete, this treatment as adjuvant therapy must be considered investigational."} {"id": "PMID:1271890", "title": "Hazards and complications of BCG immunotherapy.", "content": "The hazards and complications of BCG immunotherapy, as well as the potential for enhanced tumor growth, make it imperative that the clinician know the clinical setting in which BCG can offer therapeutic benefit. This would include the intratumor injection of localized intradermal tumor deposits of melanoma and breast cancer, chemoimmunotherapy with BCG to prolong remission in acute myelogenous leukemia, and possibly the use of BCG as an adjuvant to control minimal residual disease. Aside from these situations, it is advisable to treat patients only on clearly defined experimental protocols.", "contents": "Hazards and complications of BCG immunotherapy. The hazards and complications of BCG immunotherapy, as well as the potential for enhanced tumor growth, make it imperative that the clinician know the clinical setting in which BCG can offer therapeutic benefit. This would include the intratumor injection of localized intradermal tumor deposits of melanoma and breast cancer, chemoimmunotherapy with BCG to prolong remission in acute myelogenous leukemia, and possibly the use of BCG as an adjuvant to control minimal residual disease. Aside from these situations, it is advisable to treat patients only on clearly defined experimental protocols."} {"id": "PMID:1271969", "title": "Constituents of West African medicinal plants. XIV. Constituents of Piper guineense Schum, and Thonn.", "content": "Piper guineense Schum, and Thonn. (Piperaceae), a woodsy climber of Ghana and other parts of West Africa, has been used as a condiment and a native medicinal. Chromatography of an extract of the fruits afforded the amides piperine, N-isobutyloctadeca-trans-2-trans-4-dienamide, sylvatine, delta alpha beta-dihydropiperine, trichostachine and delta alpha beta-dihydropiperlonguminine, the last of which is a new naturally occurring amide. In a similar manner, chromatography of an acetone extract of the roots afforded piperine, trichostachine and delta alpha beta-dihydropiperine while an acetone extract of the leaves yielded dihydrocubebin, a new naturally occurring lignan.", "contents": "Constituents of West African medicinal plants. XIV. Constituents of Piper guineense Schum, and Thonn. Piper guineense Schum, and Thonn. (Piperaceae), a woodsy climber of Ghana and other parts of West Africa, has been used as a condiment and a native medicinal. Chromatography of an extract of the fruits afforded the amides piperine, N-isobutyloctadeca-trans-2-trans-4-dienamide, sylvatine, delta alpha beta-dihydropiperine, trichostachine and delta alpha beta-dihydropiperlonguminine, the last of which is a new naturally occurring amide. In a similar manner, chromatography of an acetone extract of the roots afforded piperine, trichostachine and delta alpha beta-dihydropiperine while an acetone extract of the leaves yielded dihydrocubebin, a new naturally occurring lignan."} {"id": "PMID:1271970", "title": "Rapid semi-quantitative spot test for determination of thebaine and differentiation of Papaver bracteatum from P. orientale and P. pseudo-orientale.", "content": "The alkaloids, orientalidine, oripavine, thebaine, narceine, narceine, codeine, papaverine, isothebaine, alpenigenine and morphine react with a solution of sulfuric acid containing molybdate to give specific colors. Using the acid solution permitted the differentiation of Papaver bracteatum latex from P. orientale latex and P. pseudo-orientale latex.", "contents": "Rapid semi-quantitative spot test for determination of thebaine and differentiation of Papaver bracteatum from P. orientale and P. pseudo-orientale. The alkaloids, orientalidine, oripavine, thebaine, narceine, narceine, codeine, papaverine, isothebaine, alpenigenine and morphine react with a solution of sulfuric acid containing molybdate to give specific colors. Using the acid solution permitted the differentiation of Papaver bracteatum latex from P. orientale latex and P. pseudo-orientale latex."} {"id": "PMID:1271974", "title": "Autoxidation of polyunsaturated fatty acids: II. A suggested mechanism for the formation of TBA-reactive materials from prostaglandin-like endoperoxides.", "content": "The nature and mechanism of formation of the thiobarbituric acid (TBA)-reaction material produced in the autoxidation of polyunsaturated fatty acids (PUFA) or their esters has been studied. On the basis of chemical studies and spectroscopic evidence, it is concluded that the TBA test detects malonaldehyde which arises at least in part from the acid-catalyzed or thermal decomposition or endoperoxides (2,3-dioxanorbornane compounds). These endoperosides have structures related to those of the endoperoxides produced in the biosynthetic sequence leading to prostaglandins. A mechanism is proposed in which these endoperoxides are formed in a free radical cyclization process operating in competition with hydroperoxide formation during the autoxidation of PUFA or their esters containing three or more double bonds. When 20:3 or 20:4 PUFA undergo autoxidation, some of the natural, physiologically active prostaglandins would be produced, although in very low yield, along with many other stereo- and positional isomers. Thus, it is possible that some of the complex symptoms of lipid peroxidation in vivo could be due to nonenzymatically produced prostaglandins or their steroisomers.", "contents": "Autoxidation of polyunsaturated fatty acids: II. A suggested mechanism for the formation of TBA-reactive materials from prostaglandin-like endoperoxides. The nature and mechanism of formation of the thiobarbituric acid (TBA)-reaction material produced in the autoxidation of polyunsaturated fatty acids (PUFA) or their esters has been studied. On the basis of chemical studies and spectroscopic evidence, it is concluded that the TBA test detects malonaldehyde which arises at least in part from the acid-catalyzed or thermal decomposition or endoperoxides (2,3-dioxanorbornane compounds). These endoperosides have structures related to those of the endoperoxides produced in the biosynthetic sequence leading to prostaglandins. A mechanism is proposed in which these endoperoxides are formed in a free radical cyclization process operating in competition with hydroperoxide formation during the autoxidation of PUFA or their esters containing three or more double bonds. When 20:3 or 20:4 PUFA undergo autoxidation, some of the natural, physiologically active prostaglandins would be produced, although in very low yield, along with many other stereo- and positional isomers. Thus, it is possible that some of the complex symptoms of lipid peroxidation in vivo could be due to nonenzymatically produced prostaglandins or their steroisomers."} {"id": "PMID:1271975", "title": "A radical scavenging reaction of alpha-tocopherol with methyl radical.", "content": "To study a radical scavenging reaction of alpha-tocopherol, it was reacted with methyl radical in dimethyl sulfoxide. Two main products, a geminal dimethyl cyclohexadienone and methyl ether of alpha-tocopherol, were obtained and these structures were determined by 13C nuclear magnetic resonance spectroscopy. The radical methylation data of alpha-tocopherol suggested that a delocalize radical species would be an intermediate.", "contents": "A radical scavenging reaction of alpha-tocopherol with methyl radical. To study a radical scavenging reaction of alpha-tocopherol, it was reacted with methyl radical in dimethyl sulfoxide. Two main products, a geminal dimethyl cyclohexadienone and methyl ether of alpha-tocopherol, were obtained and these structures were determined by 13C nuclear magnetic resonance spectroscopy. The radical methylation data of alpha-tocopherol suggested that a delocalize radical species would be an intermediate."} {"id": "PMID:1271976", "title": "Comparative antilipidemic effects of various ethyl 5-substituted benzofuran-, 2,3-dihydrobenzofuran-, and 3(2H)-benzofuranone-2-carboxylate analogs of clofibrate in a triton hyperlipidemic rat model.", "content": "The antilipidemic properties of certain benzofuran-, 2,3-dihydrobenzofuran-, and 3(2H)-benzofuranone-2-carboxylate analogs of clofibrate in a hyperlipidemic rat model are described. The hyperlipidemia was induced by intraperitoneal injection of Triton WR-1339. The results were analyzed in light of structural modifications as well as the lipid solubility of substituted compounds as assessed by a consideration of calculated log P values. Comparisons are made between the activity of these compounds and the activity of related cyclic analogs previously reported. Among the various compounds tested, only the 5-C1 and phenylsybstituted dihydrobenzofurans were selective against elevated serum cholesterol levels in this animal model. The data presented support the hypothesis that the cholesterol and triglyceride lowering activity of clofibrate related analogs in this animal model may be separated through a consideration of log P, conformational, and electronic changes. The proposal is advanced that relatively minor structural modification of clofibrate related analogs may lead to compounds which are not only selective in the Triton model but also to compounds which are likely to exert their effects by differing modes of action.", "contents": "Comparative antilipidemic effects of various ethyl 5-substituted benzofuran-, 2,3-dihydrobenzofuran-, and 3(2H)-benzofuranone-2-carboxylate analogs of clofibrate in a triton hyperlipidemic rat model. The antilipidemic properties of certain benzofuran-, 2,3-dihydrobenzofuran-, and 3(2H)-benzofuranone-2-carboxylate analogs of clofibrate in a hyperlipidemic rat model are described. The hyperlipidemia was induced by intraperitoneal injection of Triton WR-1339. The results were analyzed in light of structural modifications as well as the lipid solubility of substituted compounds as assessed by a consideration of calculated log P values. Comparisons are made between the activity of these compounds and the activity of related cyclic analogs previously reported. Among the various compounds tested, only the 5-C1 and phenylsybstituted dihydrobenzofurans were selective against elevated serum cholesterol levels in this animal model. The data presented support the hypothesis that the cholesterol and triglyceride lowering activity of clofibrate related analogs in this animal model may be separated through a consideration of log P, conformational, and electronic changes. The proposal is advanced that relatively minor structural modification of clofibrate related analogs may lead to compounds which are not only selective in the Triton model but also to compounds which are likely to exert their effects by differing modes of action."} {"id": "PMID:1271977", "title": "Biosynthesis of fatty acids by the carp, Cyprinus carpio L., in relation to environmental temperature.", "content": "Incorporation in vivo of sodium 1-14C-acetate into different lipid classes and fatty acids of total lipids and phospholipids of warm adapted and cold adapted carp livers was studied at 5 C and 22 C, respectively. The fatty acid composition of total lipids and phospholipids was also determined. The level of long chain polyunsaturated fatty acids in both total lipid and phospholipid fraction was higher in cold adapted fish than in warm adapted ones. The distribution of radioactivity among different lipid classes depended only on the actual incorporation of the temperature history of the animals. Livers of fish incorporated a higher percentage of radioactivity into long chain polyunsaturated fatty acids of total lipids and phospholipids in 5 C than in 22 C. The distribution of radioactivity among different fatty acids was dependent on the experimental temperature rather than on the temperature to which the fish were adapted. The results suggest that fish are able to adjust the pattern of the biosynthesis of fatty acids very rapidly to the prevailing temperature and to assure by this way the proper physicochemical properties of their membranes. The possible mechanisms involved in this rapid response are discussed.", "contents": "Biosynthesis of fatty acids by the carp, Cyprinus carpio L., in relation to environmental temperature. Incorporation in vivo of sodium 1-14C-acetate into different lipid classes and fatty acids of total lipids and phospholipids of warm adapted and cold adapted carp livers was studied at 5 C and 22 C, respectively. The fatty acid composition of total lipids and phospholipids was also determined. The level of long chain polyunsaturated fatty acids in both total lipid and phospholipid fraction was higher in cold adapted fish than in warm adapted ones. The distribution of radioactivity among different lipid classes depended only on the actual incorporation of the temperature history of the animals. Livers of fish incorporated a higher percentage of radioactivity into long chain polyunsaturated fatty acids of total lipids and phospholipids in 5 C than in 22 C. The distribution of radioactivity among different fatty acids was dependent on the experimental temperature rather than on the temperature to which the fish were adapted. The results suggest that fish are able to adjust the pattern of the biosynthesis of fatty acids very rapidly to the prevailing temperature and to assure by this way the proper physicochemical properties of their membranes. The possible mechanisms involved in this rapid response are discussed."} {"id": "PMID:1271978", "title": "Glycodihydrofusidate: biliary excretion and its effect on biliary secretion of the rat.", "content": "Glycodihydrofusidate, which has the same detergent properties a bile salts, is excreted almost exclusively by the bile duct after intravenous injection in the rat. As with bile salts, it leads to a significant (P less tthan or equal to 0.05) increase in excretion of lecithins and cholesterol (0.15 mumol lecithin and 0.026 mumol cholesterol per 1 mumol of glycodihydrofusidate excreted). In addition, this drug simulataneously inhibits excretion of both endogenous bile salts and bile pigments.", "contents": "Glycodihydrofusidate: biliary excretion and its effect on biliary secretion of the rat. Glycodihydrofusidate, which has the same detergent properties a bile salts, is excreted almost exclusively by the bile duct after intravenous injection in the rat. As with bile salts, it leads to a significant (P less tthan or equal to 0.05) increase in excretion of lecithins and cholesterol (0.15 mumol lecithin and 0.026 mumol cholesterol per 1 mumol of glycodihydrofusidate excreted). In addition, this drug simulataneously inhibits excretion of both endogenous bile salts and bile pigments."} {"id": "PMID:1271979", "title": "Quantitative determination of organic solvent soluble lipofuscin pigments in tissues.", "content": "Lipofuscin pigment determination in tissue extracts was quantitated by the use of its property of fluorescence. Chloroform:methanol tissue extracts were purified on Sephadex LH-20 columns before quantitative fluorescence measurements of the lipofuscin pigments. Interfering compounds separated by chromatography were retinol and a lower mol wt fluorescent compound. Irradiation of tissue extracts with ultraviolet light was not sufficient to eliminate the interference caused by retional and the lower mol wt compound. Purified lipofuscin pigments from blood, lung, liver, spleen, brain, heart, and kidney tissues demonstrated distinct fluorescent emission maximum at 435 nm and excitation maxima between 345 and 350 nm.", "contents": "Quantitative determination of organic solvent soluble lipofuscin pigments in tissues. Lipofuscin pigment determination in tissue extracts was quantitated by the use of its property of fluorescence. Chloroform:methanol tissue extracts were purified on Sephadex LH-20 columns before quantitative fluorescence measurements of the lipofuscin pigments. Interfering compounds separated by chromatography were retinol and a lower mol wt fluorescent compound. Irradiation of tissue extracts with ultraviolet light was not sufficient to eliminate the interference caused by retional and the lower mol wt compound. Purified lipofuscin pigments from blood, lung, liver, spleen, brain, heart, and kidney tissues demonstrated distinct fluorescent emission maximum at 435 nm and excitation maxima between 345 and 350 nm."} {"id": "PMID:1271980", "title": "Effect of lactation on lipolysis in rat adipose tissue.", "content": "The concentrations of nonesterified fatty acids and glycerol in rat parametrial adipose tissue increased at peak lactation. Adipose tissue from lactating rats showed higher rates of release of nonesterified fatty acids and glycerol when incubated in vitro than did tissue from nonlactating rats, but there was a substantial increase in the esterification of fatty acids during involution. These results support earlier evidence that fat reserves were mobilized during lactation.", "contents": "Effect of lactation on lipolysis in rat adipose tissue. The concentrations of nonesterified fatty acids and glycerol in rat parametrial adipose tissue increased at peak lactation. Adipose tissue from lactating rats showed higher rates of release of nonesterified fatty acids and glycerol when incubated in vitro than did tissue from nonlactating rats, but there was a substantial increase in the esterification of fatty acids during involution. These results support earlier evidence that fat reserves were mobilized during lactation."} {"id": "PMID:1271999", "title": "Aerobic requirements and maximum aerobic power in treadmill and track running.", "content": "Treadmill and track running comparisons were made on eight track athletes. Oxygen uptake (VO2) during steady-state and maximum aerobic power (VO2 max) were measured in a discrete series of three speeds, and at maximal effort. Running speeds were always in sequence from slowest to fastest. Expired air was collected from the runner by the Douglas-bag method, and analyzed by the Lloyd-Haldane technique. Neither VO2 max nor aerobic requirements of running were significantly different in track and treadmill determinations. There were several correlations: 1) VO2 max with body weight (r = .83 P less than .02), 2) treadmill and track determinations of VO2 max (r = .95, P less than .01) and 3) VO2 ml/kg with running velocity m/min (r = .91, P less than .01) where the regression was linear and may be represented by the equation Y = 5.36 + 0.172X, where Syx = 2.7 m102/kg. It is concluded that treadmill determinations of oxygen uptake may be validly applied to track running in calm air within the range of 180...260 m/min.", "contents": "Aerobic requirements and maximum aerobic power in treadmill and track running. Treadmill and track running comparisons were made on eight track athletes. Oxygen uptake (VO2) during steady-state and maximum aerobic power (VO2 max) were measured in a discrete series of three speeds, and at maximal effort. Running speeds were always in sequence from slowest to fastest. Expired air was collected from the runner by the Douglas-bag method, and analyzed by the Lloyd-Haldane technique. Neither VO2 max nor aerobic requirements of running were significantly different in track and treadmill determinations. There were several correlations: 1) VO2 max with body weight (r = .83 P less than .02), 2) treadmill and track determinations of VO2 max (r = .95, P less than .01) and 3) VO2 ml/kg with running velocity m/min (r = .91, P less than .01) where the regression was linear and may be represented by the equation Y = 5.36 + 0.172X, where Syx = 2.7 m102/kg. It is concluded that treadmill determinations of oxygen uptake may be validly applied to track running in calm air within the range of 180...260 m/min."} {"id": "PMID:1272000", "title": "Responses to kayak ergometer performance after kayak and bicycle ergometer training.", "content": "Ten moderately active male volunteers, age 19-30 years, completed one month of training on either a kayak or a bicycle ergometer (five men in each group). The men completed sixteen 30 minute sessions of continuous work at an intensity which maintained their HR within 85-90% of its maximum, as previously determined on the kayak ergometer. After this training period the kayak group demonstrated significant decreases in VO2, VE, HR and blood lactate in submaximal kayak ergometer work and a significant increase in VO2 during maximal kayak ergometer work. These changes contributed to a significantly higher maximal kayaking work output. The bicycle-trained group did not make any of these improvements on the kayak ergometer. However in their last training session on the bicycle ergometer they were able to work at a higher submaximal load while maintaining the same heart rate as in the first training session. It was concluded that the circulatory and metabolic adjustments to kayak work are greater with kayak training than with bicycle training.", "contents": "Responses to kayak ergometer performance after kayak and bicycle ergometer training. Ten moderately active male volunteers, age 19-30 years, completed one month of training on either a kayak or a bicycle ergometer (five men in each group). The men completed sixteen 30 minute sessions of continuous work at an intensity which maintained their HR within 85-90% of its maximum, as previously determined on the kayak ergometer. After this training period the kayak group demonstrated significant decreases in VO2, VE, HR and blood lactate in submaximal kayak ergometer work and a significant increase in VO2 during maximal kayak ergometer work. These changes contributed to a significantly higher maximal kayaking work output. The bicycle-trained group did not make any of these improvements on the kayak ergometer. However in their last training session on the bicycle ergometer they were able to work at a higher submaximal load while maintaining the same heart rate as in the first training session. It was concluded that the circulatory and metabolic adjustments to kayak work are greater with kayak training than with bicycle training."} {"id": "PMID:1272001", "title": "The cardiopulmonary capacities of young hockey players: age 10.", "content": "The cardiopulmonary capacities of 15 selected 10 year old ice hockey players were determined during a discontinuous steady-state bicycle ergometer test. During the test, heart rates, minute ventilation and oxygen uptake were monitored and the peak values at maximal capacity were recorded. Blood was collected from the median cubital vein after each maximal exercise for lactate analysis. These boys represented a select group of highly successful young hockey players. They had been involved in organized hockey for a mean of 4.4 years, 2.9 of which had been spent in a competitive league. The team has ranked 3rd in the Ontario Championships. The maximal oxygen uptake was 56.6 ml/kg-min, a value much higher than reported for healthy inactive boys and close to values reported for young athletes in other sports. Mean maximal minute ventilation reached 64.5 l/min (1.84 l/kg-min). The tests on these athletes were carried out on two separate occasions, 48 hours apart. The test-retest correlations for VO2 max was high (r = 0.81). Only the reliability of the lactate determinations was low (r = 0.24). None of the differences between the mean values for the measurements made at the first and second exercise tests were significant.", "contents": "The cardiopulmonary capacities of young hockey players: age 10. The cardiopulmonary capacities of 15 selected 10 year old ice hockey players were determined during a discontinuous steady-state bicycle ergometer test. During the test, heart rates, minute ventilation and oxygen uptake were monitored and the peak values at maximal capacity were recorded. Blood was collected from the median cubital vein after each maximal exercise for lactate analysis. These boys represented a select group of highly successful young hockey players. They had been involved in organized hockey for a mean of 4.4 years, 2.9 of which had been spent in a competitive league. The team has ranked 3rd in the Ontario Championships. The maximal oxygen uptake was 56.6 ml/kg-min, a value much higher than reported for healthy inactive boys and close to values reported for young athletes in other sports. Mean maximal minute ventilation reached 64.5 l/min (1.84 l/kg-min). The tests on these athletes were carried out on two separate occasions, 48 hours apart. The test-retest correlations for VO2 max was high (r = 0.81). Only the reliability of the lactate determinations was low (r = 0.24). None of the differences between the mean values for the measurements made at the first and second exercise tests were significant."} {"id": "PMID:1272002", "title": "A comparison of myocardial function in former athletes and non-athletes.", "content": "Heart rate (HR), total electromechanical systole (Q-S2), left ventricular ejection time (LVET), pre-ejection period (PEP), and diastole (D) were compared in 350 former athletes and 156 non-athletes, age 27-74. The two cohorts had been equated according to habitual leisure time physical activity. Former athletes exhibited significantly longer Q-S2 and PEP at rest, and significantly lower HR and lengthened Q-S2, LVET, PEP, and D at one minute following a standard two minute step test (less than 0.05). Significantly differences were observed between athletes and non-athletes in the light and moderate activity categories. There were no significant differences between former athletes and non-athletes currently engaged in strenuous leisure time physical activity. Comparisons were made among the three levels of habitual leisure time physical activity with each group and revealed that HR was lower and Q-S2, LVET, PEP, and D were longer at rest and following exercise as the level of physical activity increased. There were more significant differences among former athletes than among non-athletes. Most of these differences were between light to moderate and light to strenuous levels of activity. The evidence suggests an advantage in myocardial function among former athletes compared to their non-athlete counterparts.", "contents": "A comparison of myocardial function in former athletes and non-athletes. Heart rate (HR), total electromechanical systole (Q-S2), left ventricular ejection time (LVET), pre-ejection period (PEP), and diastole (D) were compared in 350 former athletes and 156 non-athletes, age 27-74. The two cohorts had been equated according to habitual leisure time physical activity. Former athletes exhibited significantly longer Q-S2 and PEP at rest, and significantly lower HR and lengthened Q-S2, LVET, PEP, and D at one minute following a standard two minute step test (less than 0.05). Significantly differences were observed between athletes and non-athletes in the light and moderate activity categories. There were no significant differences between former athletes and non-athletes currently engaged in strenuous leisure time physical activity. Comparisons were made among the three levels of habitual leisure time physical activity with each group and revealed that HR was lower and Q-S2, LVET, PEP, and D were longer at rest and following exercise as the level of physical activity increased. There were more significant differences among former athletes than among non-athletes. Most of these differences were between light to moderate and light to strenuous levels of activity. The evidence suggests an advantage in myocardial function among former athletes compared to their non-athlete counterparts."} {"id": "PMID:1272003", "title": "Serum testosterone, body composition, and strength of young adults.", "content": "The relationship between serum testosterone (ST), body composition, and static strength was studied in 26 college females and 16 male college football players. In addition, the transient effect of weight training on ST was studied in 10 college males (5 skilled and 5 unskilled weight trainers), 12 male high school students, and 5 female college students. ST, measured by radioimmunoassay, ranged from 333.7 to 848.1 ng/100 ml in males, and from 32.8 to 121.5 n/100 ml in females. The high school subjects had significantly lower levels of ST. Correlations between serum testosterone, body composition (measured by densitometry), and static strength (grip and backlift) were nonsignificant in males and females. Comparisons of subjects with the highest and lowest levels of testosterone within each sex showed no significant differences in strength or body composition. Serum testosterone increased 111.4 +/- 96.l ng/100 ml (X +/- SX) following a weight training session in the male college group, but failed to increase in the college females or high school males. There were no significant differences in testosterone increases between the skilled and unskilled male weight trainers. Maximal exertion may be necessary for an increase in serum testosterone to occur. Lack of an increase in testosterone by high school males or college females may have been due to a submaximal effort during the weight training exercise.", "contents": "Serum testosterone, body composition, and strength of young adults. The relationship between serum testosterone (ST), body composition, and static strength was studied in 26 college females and 16 male college football players. In addition, the transient effect of weight training on ST was studied in 10 college males (5 skilled and 5 unskilled weight trainers), 12 male high school students, and 5 female college students. ST, measured by radioimmunoassay, ranged from 333.7 to 848.1 ng/100 ml in males, and from 32.8 to 121.5 n/100 ml in females. The high school subjects had significantly lower levels of ST. Correlations between serum testosterone, body composition (measured by densitometry), and static strength (grip and backlift) were nonsignificant in males and females. Comparisons of subjects with the highest and lowest levels of testosterone within each sex showed no significant differences in strength or body composition. Serum testosterone increased 111.4 +/- 96.l ng/100 ml (X +/- SX) following a weight training session in the male college group, but failed to increase in the college females or high school males. There were no significant differences in testosterone increases between the skilled and unskilled male weight trainers. Maximal exertion may be necessary for an increase in serum testosterone to occur. Lack of an increase in testosterone by high school males or college females may have been due to a submaximal effort during the weight training exercise."} {"id": "PMID:1272004", "title": "A comparison of concentric and eccentric muscle training.", "content": "Eight male university students served as subjects in an investigation designed to develop strength using two different muscle training routines over a six week period. The subjects trained the arm and leg on one side of their bodies using concentric contractions and the arm and leg on the opposite side of their bodies with identical exercises using eccentric contractions. Concentric movements were against a resistance 80% of one-repetition-maximum (1-Rm) for 10 repetitions and two sets; eccentric movements were against a force of 120% of concentric 1-RM for 6 repetitions and two sets. Both routines produced significant gains in strength in all subjects, but neither training procedure produced dynamic or static strength gains significantly different from the other. Subjective evaluations by the subjects indicated that the eccentric training movements were easier to perform than the concentric training movements.", "contents": "A comparison of concentric and eccentric muscle training. Eight male university students served as subjects in an investigation designed to develop strength using two different muscle training routines over a six week period. The subjects trained the arm and leg on one side of their bodies using concentric contractions and the arm and leg on the opposite side of their bodies with identical exercises using eccentric contractions. Concentric movements were against a resistance 80% of one-repetition-maximum (1-Rm) for 10 repetitions and two sets; eccentric movements were against a force of 120% of concentric 1-RM for 6 repetitions and two sets. Both routines produced significant gains in strength in all subjects, but neither training procedure produced dynamic or static strength gains significantly different from the other. Subjective evaluations by the subjects indicated that the eccentric training movements were easier to perform than the concentric training movements."} {"id": "PMID:1272005", "title": "An early stretching routine for calf muscle strains.", "content": "Four hundred patients, average age 35 attended for treatment of strains to calf muscles. There was an average delay of 8 days before presenting. The treatment involved several repetitions of a routine involving ice or short wave for pain relief, passive stretching, ultra sound and exercises firstly for the antagonists and then the injured muscle in that order. Quadriceps exercises and correct walking were performed to ensure fitness for sport after cure. The average treatment time was 6 days. Prevention of disability was aided by early treatment, stretching before activity and exercises to increase strength in the calf. The recurrence rate was 1%.", "contents": "An early stretching routine for calf muscle strains. Four hundred patients, average age 35 attended for treatment of strains to calf muscles. There was an average delay of 8 days before presenting. The treatment involved several repetitions of a routine involving ice or short wave for pain relief, passive stretching, ultra sound and exercises firstly for the antagonists and then the injured muscle in that order. Quadriceps exercises and correct walking were performed to ensure fitness for sport after cure. The average treatment time was 6 days. Prevention of disability was aided by early treatment, stretching before activity and exercises to increase strength in the calf. The recurrence rate was 1%."} {"id": "PMID:1272006", "title": "Aerodynamic drag analysis of runners.", "content": "A model is presented for the determination of aerodynamic drag forces on runners. The model consists of a series of conjugated circular cylinders, to stimulate the trunk and appendages, and a sphere to stimulate the head. Results are presented for three runners representing respectively, adult American males in the 2.5, 50 and 97.5 percentiles of the population. It is found that power dissipated in overcoming air resistance for these three runners ranges from 0.33 to 0.49 horsepower at a sprint speed comparable to the current world's record for one hundred yards. In addition an alternate model, consisting of a single circular cylinder, is presented that simplifies the determination of total aerodynamics drag. The accuracy of this model is determined by comparing results for total drag with those found with the more complex model. It is found that the error ranges from 5 to 8.9 percent.", "contents": "Aerodynamic drag analysis of runners. A model is presented for the determination of aerodynamic drag forces on runners. The model consists of a series of conjugated circular cylinders, to stimulate the trunk and appendages, and a sphere to stimulate the head. Results are presented for three runners representing respectively, adult American males in the 2.5, 50 and 97.5 percentiles of the population. It is found that power dissipated in overcoming air resistance for these three runners ranges from 0.33 to 0.49 horsepower at a sprint speed comparable to the current world's record for one hundred yards. In addition an alternate model, consisting of a single circular cylinder, is presented that simplifies the determination of total aerodynamics drag. The accuracy of this model is determined by comparing results for total drag with those found with the more complex model. It is found that the error ranges from 5 to 8.9 percent."} {"id": "PMID:1272007", "title": "Physiological variables during 10 years of endurance exercise.", "content": "The reported decline in Physical Working Capacity (PWC) max is from 9-15 percent during the ages of 45 to 55 years. The use of vigorous physical activity to prevent this decline and to possibly protect against fatal myocardial infarction has been suggested. The purpose of this study was to investigate the effect of an endurance type exercise program on the maximal PWC of middle-aged men during a 10 year span. Sixteen men, initially 32-56 years (M-44.6), were trained with running or swimming at an intensity above 60 percent of VO2 max during a 10 year period. The average weekly running distance was 15 miles (25 km). The criterion for PWC was directly measured VO2 using the Douglas Bag/Scholander technique. No changes were observed in body weight, resting heart rate (HR), or resting blood pressure (BP). Maximal HR declined 7 beats per minute in 10 years. Pulmonary ventilation (STPD) increased approximately 18 percent. Mean VO2 max was essentially unchanged, 3.376 and 3.303 1/min STPD. VO2 max related to body weight was 43.7 initially and 44.4 ml/min-kg after 10 years. It was concluded that the usual 9-15 percent decline in PWC or VO2 max from age 45 to 55 years can be forestalled by regular endurance exercise. The results may have implications for protecting against heart attacks.", "contents": "Physiological variables during 10 years of endurance exercise. The reported decline in Physical Working Capacity (PWC) max is from 9-15 percent during the ages of 45 to 55 years. The use of vigorous physical activity to prevent this decline and to possibly protect against fatal myocardial infarction has been suggested. The purpose of this study was to investigate the effect of an endurance type exercise program on the maximal PWC of middle-aged men during a 10 year span. Sixteen men, initially 32-56 years (M-44.6), were trained with running or swimming at an intensity above 60 percent of VO2 max during a 10 year period. The average weekly running distance was 15 miles (25 km). The criterion for PWC was directly measured VO2 using the Douglas Bag/Scholander technique. No changes were observed in body weight, resting heart rate (HR), or resting blood pressure (BP). Maximal HR declined 7 beats per minute in 10 years. Pulmonary ventilation (STPD) increased approximately 18 percent. Mean VO2 max was essentially unchanged, 3.376 and 3.303 1/min STPD. VO2 max related to body weight was 43.7 initially and 44.4 ml/min-kg after 10 years. It was concluded that the usual 9-15 percent decline in PWC or VO2 max from age 45 to 55 years can be forestalled by regular endurance exercise. The results may have implications for protecting against heart attacks."} {"id": "PMID:1272008", "title": "Energy cost of running and walking in young women.", "content": "The energy cost of level walking and level and grade running was determined in 7 active women with max VO2 = 50.7 ml/kg-min. Speeds investigated were 4 to 8 km/hr walking and 8 to 14.5 km/hr running. The validity coefficients of several procedures for estimating energy expenditure during locomotion [4 for running (6)(11)(16)(17); 3 for walking (6)(12)(17)] were determined. Correlation coefficients between actual and predicted values were 0.949 to 0.951 with standard errors of estimate 0.79 to 0.80 kcal/kg-hour for walking and 0.856 to 0.975 with standard errors of estimate 0.40 to 0.60 kcal/kg-hour for running. VO2 and kcal energy cost values were similar to those previously reported on men at equivalent walking and running speeds. Efficiency of running based on lift work done was about 25%. Lift work for women was slightly less than values previously reported for men at walking but was slightly more at running. These differences did not appear to have a significant effect on energy expenditure.", "contents": "Energy cost of running and walking in young women. The energy cost of level walking and level and grade running was determined in 7 active women with max VO2 = 50.7 ml/kg-min. Speeds investigated were 4 to 8 km/hr walking and 8 to 14.5 km/hr running. The validity coefficients of several procedures for estimating energy expenditure during locomotion [4 for running (6)(11)(16)(17); 3 for walking (6)(12)(17)] were determined. Correlation coefficients between actual and predicted values were 0.949 to 0.951 with standard errors of estimate 0.79 to 0.80 kcal/kg-hour for walking and 0.856 to 0.975 with standard errors of estimate 0.40 to 0.60 kcal/kg-hour for running. VO2 and kcal energy cost values were similar to those previously reported on men at equivalent walking and running speeds. Efficiency of running based on lift work done was about 25%. Lift work for women was slightly less than values previously reported for men at walking but was slightly more at running. These differences did not appear to have a significant effect on energy expenditure."} {"id": "PMID:1272069", "title": "The natural history of extramedullary plasmacytoma and its relation to solitary myeloma of bone and myelomatosis.", "content": "From this study I suggest that extramedullary plasmacytoma (EMP) shows several important differences from myelomatosis and solitary myeloma of bone (SMB) which can be summarized as follows: 1. A marked preference for the primary tumor to present in a particular site, namely the upper air passages. 2. A high incidence of metastatic spread to soft tissues. 3. Spread to bone occurs frequently but shows no preference for bones containing active hematopoietic tissue and widespread bone-marrow involvement occurs only occasionally. 4. Prolonged survival may be achieved with therapy for local disease. 5. Vigorous treatment for disseminated disease can be given and may result in longer remissions than those usually seen in myelomatosis. Healing of bone lesions has been observed on several occasions. It is concluded also that SMB constitutes a rather unusual presentation of myelomatosis but is essentially the same disease process.", "contents": "The natural history of extramedullary plasmacytoma and its relation to solitary myeloma of bone and myelomatosis. From this study I suggest that extramedullary plasmacytoma (EMP) shows several important differences from myelomatosis and solitary myeloma of bone (SMB) which can be summarized as follows: 1. A marked preference for the primary tumor to present in a particular site, namely the upper air passages. 2. A high incidence of metastatic spread to soft tissues. 3. Spread to bone occurs frequently but shows no preference for bones containing active hematopoietic tissue and widespread bone-marrow involvement occurs only occasionally. 4. Prolonged survival may be achieved with therapy for local disease. 5. Vigorous treatment for disseminated disease can be given and may result in longer remissions than those usually seen in myelomatosis. Healing of bone lesions has been observed on several occasions. It is concluded also that SMB constitutes a rather unusual presentation of myelomatosis but is essentially the same disease process."} {"id": "PMID:1272070", "title": "Ischemic necrosis of bone in systemic lupus erythematosus.", "content": "Twenty-three patients with systemic lupus erythematosus (SLE) and ischemic bone necrosis are reported. All patients had received corticosteroids prior to the onset of ischemic necrosis, although one patient had received none for 13 years previously. Nineteen (83%) patients had multiple bone lesions including the femoral heads in 21 (91%) which were bilaterally involved in 15. In addition, humeral heads were affected in seven patients and the tibial plateaus, in three. The most striking feature of this group was the high incidence of Raynaud's phenomemon present in 14 (61%) of the 23 patients. Furthermore, central nervous system involvement was present in 10 (43%) patients, more prominent in those without Raynaud's (67%) than in those with vasospasm (29%). Thus, 20 of the 23 patients, or 87%, evidenced vascular abnormalities either in the form of Raynaud's phenomenon and/or systemic vasculitis. The pathogenesis of ischemic bone necrosis is discussed. In SLE, vasospasm or vasculitis, or both, augmented by corticosteroid therapy, could impede the microcirculation and result in the ischemic lesion.", "contents": "Ischemic necrosis of bone in systemic lupus erythematosus. Twenty-three patients with systemic lupus erythematosus (SLE) and ischemic bone necrosis are reported. All patients had received corticosteroids prior to the onset of ischemic necrosis, although one patient had received none for 13 years previously. Nineteen (83%) patients had multiple bone lesions including the femoral heads in 21 (91%) which were bilaterally involved in 15. In addition, humeral heads were affected in seven patients and the tibial plateaus, in three. The most striking feature of this group was the high incidence of Raynaud's phenomemon present in 14 (61%) of the 23 patients. Furthermore, central nervous system involvement was present in 10 (43%) patients, more prominent in those without Raynaud's (67%) than in those with vasospasm (29%). Thus, 20 of the 23 patients, or 87%, evidenced vascular abnormalities either in the form of Raynaud's phenomenon and/or systemic vasculitis. The pathogenesis of ischemic bone necrosis is discussed. In SLE, vasospasm or vasculitis, or both, augmented by corticosteroid therapy, could impede the microcirculation and result in the ischemic lesion."} {"id": "PMID:1272071", "title": "Total body sodium and chlorine in normal adults.", "content": "Absolute levels of total body sodium (TBNa) and total body chlorine (TBCl) were determined in 81 normal adults (39 males, 42 females) by means of total body neutron activation analysis (TBNAA). The ages of the subjects ranged from 30 to 90 yr. The mean values for both TBNa and TBCl remained relatively constant throughout the age span studied for males, but decreased slightly for females over 60 yr of age. In order for the absolute measurements of Na and Cl to be of clinical value, the values must be compared to a predicted value based on the sex and body habitus of the individual. Normalization of TBNa values relative to body dimensions (weight, height, body surface area) were evaluated. In addition, TBNa was related to total body calcium (TBCa), which reflects skeletal mass, and TBK, which reflects muscle, or lean body mass. Normalization in terms of a linear combination of the TBCa and TBK was found to be the most satisfactory of all those studied. Sodium excess, NaES, defined as the amount of body sodium (mEq) in excess of body chlorine (mEq) was determined. Sodium excess correlated well with total body calcium. Values for total body sodium and chlorine obtained in the present study were compared with values previously reported in the literature.", "contents": "Total body sodium and chlorine in normal adults. Absolute levels of total body sodium (TBNa) and total body chlorine (TBCl) were determined in 81 normal adults (39 males, 42 females) by means of total body neutron activation analysis (TBNAA). The ages of the subjects ranged from 30 to 90 yr. The mean values for both TBNa and TBCl remained relatively constant throughout the age span studied for males, but decreased slightly for females over 60 yr of age. In order for the absolute measurements of Na and Cl to be of clinical value, the values must be compared to a predicted value based on the sex and body habitus of the individual. Normalization of TBNa values relative to body dimensions (weight, height, body surface area) were evaluated. In addition, TBNa was related to total body calcium (TBCa), which reflects skeletal mass, and TBK, which reflects muscle, or lean body mass. Normalization in terms of a linear combination of the TBCa and TBK was found to be the most satisfactory of all those studied. Sodium excess, NaES, defined as the amount of body sodium (mEq) in excess of body chlorine (mEq) was determined. Sodium excess correlated well with total body calcium. Values for total body sodium and chlorine obtained in the present study were compared with values previously reported in the literature."} {"id": "PMID:1272072", "title": "Free serum histidine levels in patients with rheumatoid arthritis and control subjects following an oral load of free L-histidine.", "content": "A dose of 3.7 g of free-L-histidine was administered by mouth to 26 patients with active rheumatoid arthritis and to 29 control subjects. The patients with rheumatoid arthritis had a statistically significant (p=10(-12)) lower pretreatment concentration of free histidine in serum (1.20 mg/100 ml, SE=0.04) than the control subjects (1.90 mg/100 ml, SE=0.06). However, there were no statistically significant differences between rheumatoid and control subjects with respect to the serum histidine concentrations 1 hr, 3 hr, and 4 hr after the ingestion of L-histidine. The changes in the serum histidine concentrations at 1 hr, 3 hr, and 4 hr (compared to the pretest values) were also not significantly different in the patients with rheumatoid arthritis relative to the control subjects. This study suggests that the subnormal free serum histidine concentration of rheumatoid arthritis is not associated with abnormal serum levels of free histidine following an oral load of free histidine.", "contents": "Free serum histidine levels in patients with rheumatoid arthritis and control subjects following an oral load of free L-histidine. A dose of 3.7 g of free-L-histidine was administered by mouth to 26 patients with active rheumatoid arthritis and to 29 control subjects. The patients with rheumatoid arthritis had a statistically significant (p=10(-12)) lower pretreatment concentration of free histidine in serum (1.20 mg/100 ml, SE=0.04) than the control subjects (1.90 mg/100 ml, SE=0.06). However, there were no statistically significant differences between rheumatoid and control subjects with respect to the serum histidine concentrations 1 hr, 3 hr, and 4 hr after the ingestion of L-histidine. The changes in the serum histidine concentrations at 1 hr, 3 hr, and 4 hr (compared to the pretest values) were also not significantly different in the patients with rheumatoid arthritis relative to the control subjects. This study suggests that the subnormal free serum histidine concentration of rheumatoid arthritis is not associated with abnormal serum levels of free histidine following an oral load of free histidine."} {"id": "PMID:1272073", "title": "Nucleation and growth of brushite and calcium oxalate in urine of stone-formers.", "content": "The physicochemical factors involved in the formation of calcium-containing renal stones have been elucidated previously and some of the techniques for their quantitation are currently available. Accordingly, urinary activity product ratio (state of saturation), formation product ratio (limit of metastability), and crystal growth of brushite and calcium oxalate in 24-hr urine samples were compared between a control group without stones and stone-forming groups composed of patients with absorptive hypercalciuria, normocalciuric nephrolithiasis, and primary hyperparathyroidism. The activity product ratios of brushite and calcium oxalate were significantly elevated in stone-forming groups, largely because of the high renal excretion of calcium. The formation product ratios were reduced in most stone-forming groups, and the crystal growth was increased in the group with primary hyperparathyroidism. Thus, the physicochemical environment of urine in stone-forming groups was favorable to the nucleation of the nidi of brushite and calcium oxalate; in primary hyperparathyroidism, it may be conducive to the subsequent growth of nidi as well.", "contents": "Nucleation and growth of brushite and calcium oxalate in urine of stone-formers. The physicochemical factors involved in the formation of calcium-containing renal stones have been elucidated previously and some of the techniques for their quantitation are currently available. Accordingly, urinary activity product ratio (state of saturation), formation product ratio (limit of metastability), and crystal growth of brushite and calcium oxalate in 24-hr urine samples were compared between a control group without stones and stone-forming groups composed of patients with absorptive hypercalciuria, normocalciuric nephrolithiasis, and primary hyperparathyroidism. The activity product ratios of brushite and calcium oxalate were significantly elevated in stone-forming groups, largely because of the high renal excretion of calcium. The formation product ratios were reduced in most stone-forming groups, and the crystal growth was increased in the group with primary hyperparathyroidism. Thus, the physicochemical environment of urine in stone-forming groups was favorable to the nucleation of the nidi of brushite and calcium oxalate; in primary hyperparathyroidism, it may be conducive to the subsequent growth of nidi as well."} {"id": "PMID:1272074", "title": "Blood D-3-hydroxybutyrate and the regulation of plasma concentrations of free fatty acids in the fasted rat.", "content": "Acetoacetate or DL-3-hydroxybutyrate were infused into fasted rats at rates comparable to the endogenous rate of ketone body release. Blood samples taken before and during infusion were analyzed for concentrations of ketone bodies, free fatty acids, and immunoreactive insulin. During infusion of acetoacetate or DL-3-hydroxybutyrate, blood concentrations of total ketone bodies doubled. While the HBA/AcAc ratios remained constant in rats infused with DL-3-hydroxybutyrate, the ratios decreased significantly during infusion of acetoacetate, reflecting increases in acetoacetate concentrations without proportionate increases in concentrations of D-3-hydroxybutyrate. Blood concentrations of free fatty acids decreased more rapidly in the rats infused with DL-3-hydroxybutyrate than in the rats infused with acetoacetate. The decrease in free fatty acid concentrations was related to increases in blood D-3-hydroxybutyrate in both the DL-3-hydroxybutyrate-infused rats and in the acetoacetate-infused rats. Plasma immunoreactive insulin concentrations were significantly higher in the DL-3-hydroxybutyrate-infused rats than in the acetoacetate-infused rats. Acetoacetate and DL-3-hydroxybutyrate were infused into depancreatized, functionally hepatectomized fasted rats at rates comparable to those used in the intact fasted rats. Only small decreases in free fatty acid concentrations were observed during infusion. From these experiments it was concluded that increases in blood concentrations of D-3-hydroxybutyrate were more effective than acetoacetate in causing decreases in free fatty acid concentrations in the fasting rat. The pancreas is required for this effect.", "contents": "Blood D-3-hydroxybutyrate and the regulation of plasma concentrations of free fatty acids in the fasted rat. Acetoacetate or DL-3-hydroxybutyrate were infused into fasted rats at rates comparable to the endogenous rate of ketone body release. Blood samples taken before and during infusion were analyzed for concentrations of ketone bodies, free fatty acids, and immunoreactive insulin. During infusion of acetoacetate or DL-3-hydroxybutyrate, blood concentrations of total ketone bodies doubled. While the HBA/AcAc ratios remained constant in rats infused with DL-3-hydroxybutyrate, the ratios decreased significantly during infusion of acetoacetate, reflecting increases in acetoacetate concentrations without proportionate increases in concentrations of D-3-hydroxybutyrate. Blood concentrations of free fatty acids decreased more rapidly in the rats infused with DL-3-hydroxybutyrate than in the rats infused with acetoacetate. The decrease in free fatty acid concentrations was related to increases in blood D-3-hydroxybutyrate in both the DL-3-hydroxybutyrate-infused rats and in the acetoacetate-infused rats. Plasma immunoreactive insulin concentrations were significantly higher in the DL-3-hydroxybutyrate-infused rats than in the acetoacetate-infused rats. Acetoacetate and DL-3-hydroxybutyrate were infused into depancreatized, functionally hepatectomized fasted rats at rates comparable to those used in the intact fasted rats. Only small decreases in free fatty acid concentrations were observed during infusion. From these experiments it was concluded that increases in blood concentrations of D-3-hydroxybutyrate were more effective than acetoacetate in causing decreases in free fatty acid concentrations in the fasting rat. The pancreas is required for this effect."} {"id": "PMID:1272075", "title": "[A method of microphotometry with TV-image analysing systems (author's transl)].", "content": "In scanning microphotometry only a small spot in the specimen is illuminated at the same time. However, lamp and optical system are designed to transfer 10(5) to 10(6) times more information at once. It is shown, that correct and reproducible results can be attained with stimultaneous illumination of the field received by a TV-camera. It is necessary to calibrate for stray light. Thus the high speed of measurement of TV-Systems can be used for microphotometry.", "contents": "[A method of microphotometry with TV-image analysing systems (author's transl)]. In scanning microphotometry only a small spot in the specimen is illuminated at the same time. However, lamp and optical system are designed to transfer 10(5) to 10(6) times more information at once. It is shown, that correct and reproducible results can be attained with stimultaneous illumination of the field received by a TV-camera. It is necessary to calibrate for stray light. Thus the high speed of measurement of TV-Systems can be used for microphotometry."} {"id": "PMID:1272088", "title": "Design of an ultrahigh-energy hydrogen thyratron/SCR research defibrillator.", "content": "The design features of an ultrahigh-energy research defibrillator are described. Three voltage sources are used. The first is a 60-Hz supply of adjustable amplitude and duration for inducing fibrillation. The second source uses an 18.000-joule capacitor bank which can be charged to 800, 1600, or 2400 volts. SCRs in series with the chest are used to initiate the discharge, and SCRs shunting the capacitor bank terminate the discharge. The third source employs another 18,000-joule capacitor bank which can be charged to 5000, 10,000 or 15,000 volts. In this source, large ceramic-enveloped hydrogen thyratrons are used for both initiating and terminating the discharge. In the second and third sources, which can deliver rectangular, trapezoidal, truncated exponential, or untruncated exponential waveforms, capacitor charge time is 10 sec and the duration of the delivered shock is continuously adjustable from 100 musec through 1 sec.", "contents": "Design of an ultrahigh-energy hydrogen thyratron/SCR research defibrillator. The design features of an ultrahigh-energy research defibrillator are described. Three voltage sources are used. The first is a 60-Hz supply of adjustable amplitude and duration for inducing fibrillation. The second source uses an 18.000-joule capacitor bank which can be charged to 800, 1600, or 2400 volts. SCRs in series with the chest are used to initiate the discharge, and SCRs shunting the capacitor bank terminate the discharge. The third source employs another 18,000-joule capacitor bank which can be charged to 5000, 10,000 or 15,000 volts. In this source, large ceramic-enveloped hydrogen thyratrons are used for both initiating and terminating the discharge. In the second and third sources, which can deliver rectangular, trapezoidal, truncated exponential, or untruncated exponential waveforms, capacitor charge time is 10 sec and the duration of the delivered shock is continuously adjustable from 100 musec through 1 sec."} {"id": "PMID:1272089", "title": "Transthoracic impedance to direct current discharge: effect of repeated countershocks.", "content": "The effect of repeated countershocks on transthoracic apparent impedance to direct current (dc) defibrillator discharges was studied. Repeated dc countershocks result in a progressive decrease in transthoracic apparent impedance that is dependent upon the time interval between countershocks. This decrease was significantly greater in the group of animals shocked at 3-min intervals compared to the groups shocked at 15-sec intervals (P less than 0.001) or at 1-min intervals (P less than 0.005). Since lowered impedance results in higher delivered current for the same energy setting on a defibrillator, this observation may help to explain the enhanced effectiveness of repeated countershocks in defibrillation. Plots of simultaneous current against voltage during transthoracic dc discharge revealed that the current lagged slightly behind voltage during the rising phase of the recording, but that current and voltage were nearly simultaneous during the falling phase. This effect appears to be similar to an ionization phenomenon in that the effective impedance asymptotically approaches a lower value with increasingly applied voltage. This might explain why transthoracic impedance is highest at low energy countershocks and decreases with higher energy countershock.", "contents": "Transthoracic impedance to direct current discharge: effect of repeated countershocks. The effect of repeated countershocks on transthoracic apparent impedance to direct current (dc) defibrillator discharges was studied. Repeated dc countershocks result in a progressive decrease in transthoracic apparent impedance that is dependent upon the time interval between countershocks. This decrease was significantly greater in the group of animals shocked at 3-min intervals compared to the groups shocked at 15-sec intervals (P less than 0.001) or at 1-min intervals (P less than 0.005). Since lowered impedance results in higher delivered current for the same energy setting on a defibrillator, this observation may help to explain the enhanced effectiveness of repeated countershocks in defibrillation. Plots of simultaneous current against voltage during transthoracic dc discharge revealed that the current lagged slightly behind voltage during the rising phase of the recording, but that current and voltage were nearly simultaneous during the falling phase. This effect appears to be similar to an ionization phenomenon in that the effective impedance asymptotically approaches a lower value with increasingly applied voltage. This might explain why transthoracic impedance is highest at low energy countershocks and decreases with higher energy countershock."} {"id": "PMID:1272090", "title": "Electode catheter for transvenous defibrillation.", "content": "Development of an implantable automatic defibrillator is dependent on achieving a reduction in the energy required for defibrillation, which is related to an optimal electrode configuration. This study investigated the use of a transvenous catheter electrode utilizing the damped sinusoidal waveform; compared the defibrillation effectiveness of varying the configuration of the four electrode units and of using a catheter/subcutaneous metal plate combination; and determined the lowest energy level necessary for near consistent transvenous defibrillation.", "contents": "Electode catheter for transvenous defibrillation. Development of an implantable automatic defibrillator is dependent on achieving a reduction in the energy required for defibrillation, which is related to an optimal electrode configuration. This study investigated the use of a transvenous catheter electrode utilizing the damped sinusoidal waveform; compared the defibrillation effectiveness of varying the configuration of the four electrode units and of using a catheter/subcutaneous metal plate combination; and determined the lowest energy level necessary for near consistent transvenous defibrillation."} {"id": "PMID:1272091", "title": "The prediction of the impedance of the thorax to defibrillating current.", "content": "In this paper a technique for predicting thoracic impedance to defibrillator pulses is described. The impedance to low-current (1.0 mA) high-frequency (10-500kHz) sinusoidal current is used as an indicator of the impedance of the thorax to high-current, damped sinusoidal waveform pulses. Results from 71 dogs to which defibrillator shocks of 4 to 220 A peak current were applied show that thoracic impedance can be predicted by this method. This information indicates that it is possible to design a defibrillator that can automatically measure chest impedance prior to a defibrillation shock and deliver a predetermined peak current to the subject.", "contents": "The prediction of the impedance of the thorax to defibrillating current. In this paper a technique for predicting thoracic impedance to defibrillator pulses is described. The impedance to low-current (1.0 mA) high-frequency (10-500kHz) sinusoidal current is used as an indicator of the impedance of the thorax to high-current, damped sinusoidal waveform pulses. Results from 71 dogs to which defibrillator shocks of 4 to 220 A peak current were applied show that thoracic impedance can be predicted by this method. This information indicates that it is possible to design a defibrillator that can automatically measure chest impedance prior to a defibrillation shock and deliver a predetermined peak current to the subject."} {"id": "PMID:1272097", "title": "Observations on wound drainage with a review of the literature.", "content": "Observations have been made on the choice of wound drainage in 119 general surgical or urological procedures performed by surgeons in a general hospital. Complications of the drains used are reported. Softer and more pliable drains appear to cause less morbidity than the stiffer, more rigid variety. The literature dealing with drainage is reviewed.", "contents": "Observations on wound drainage with a review of the literature. Observations have been made on the choice of wound drainage in 119 general surgical or urological procedures performed by surgeons in a general hospital. Complications of the drains used are reported. Softer and more pliable drains appear to cause less morbidity than the stiffer, more rigid variety. The literature dealing with drainage is reviewed."} {"id": "PMID:1272092", "title": "Considerations in the development of the automatic implantable defibrillator.", "content": "A highly reliable ventricular fibrillation detector and a satisfactory electrode system for delivering defibrillating pulses to the heart play a central role in the development of an automatic implantable defibrillator suitable for clinical use. Among the four implanted electrode designs tested, the combination of an electrode placed in the superior vena cava with a conformal electrode on the apex of the heart provided satisfactory defibrillation thresholds with ease of implantation. A new sensing method is also described for which an electrogram derived from the defibrillating electrodes is used as input. A form of a density function is developed for a filtered version of the input, ventricular fibrillation being characterized by a density curve lacking a large peak occurring at a level corresponding to the baseline of the filtered signal. These ideas are being incorporated into the design of a prototype implantable defibrillator delivering pulses of 24 joules.", "contents": "Considerations in the development of the automatic implantable defibrillator. A highly reliable ventricular fibrillation detector and a satisfactory electrode system for delivering defibrillating pulses to the heart play a central role in the development of an automatic implantable defibrillator suitable for clinical use. Among the four implanted electrode designs tested, the combination of an electrode placed in the superior vena cava with a conformal electrode on the apex of the heart provided satisfactory defibrillation thresholds with ease of implantation. A new sensing method is also described for which an electrogram derived from the defibrillating electrodes is used as input. A form of a density function is developed for a filtered version of the input, ventricular fibrillation being characterized by a density curve lacking a large peak occurring at a level corresponding to the baseline of the filtered signal. These ideas are being incorporated into the design of a prototype implantable defibrillator delivering pulses of 24 joules."} {"id": "PMID:1272098", "title": "Headaches in relation to the eyes.", "content": "An analysis of patients presenting with headache shows that in very few cases is the headache related to refractive error. Similarly in presbyopia and hypermetropia headaches are infrequent. A significant proportion (up to 50%) of those patients presenting with a close relationship of headache to accommodation difficulty can be helped by glasses. It is postulated that ciliary muscle contraction per se is effortless and symptomless and that any headaches produced are due to associated contraction of the scalp muscles.", "contents": "Headaches in relation to the eyes. An analysis of patients presenting with headache shows that in very few cases is the headache related to refractive error. Similarly in presbyopia and hypermetropia headaches are infrequent. A significant proportion (up to 50%) of those patients presenting with a close relationship of headache to accommodation difficulty can be helped by glasses. It is postulated that ciliary muscle contraction per se is effortless and symptomless and that any headaches produced are due to associated contraction of the scalp muscles."} {"id": "PMID:1272099", "title": "Infantile autism: the incidence of national groups in a New South Wales survey.", "content": "In a survey on the occurrence of infantile autism in New South Wales it was found that 21-9% of children had at least one foreign-born parent whose native language was not English. In terms of population incidence for New South Wales, Italy and Yugoslavia were under-represented while Greece and Germany were significantly over-represented. The stresses faced by migrants in a new country were discussed in terms of possible contributing agents and in particular, the cultural traditions of the Greeks and their adjustment problems were highlighted. It was suggested that the stresses of cultural change and the socioeconomic pressures borne by the parents resulted in deprivation of their children who were also exposed to a confused language environment, and that a combination of these variables could lead to decompensation into an autistic state in an already vulnerable child.", "contents": "Infantile autism: the incidence of national groups in a New South Wales survey. In a survey on the occurrence of infantile autism in New South Wales it was found that 21-9% of children had at least one foreign-born parent whose native language was not English. In terms of population incidence for New South Wales, Italy and Yugoslavia were under-represented while Greece and Germany were significantly over-represented. The stresses faced by migrants in a new country were discussed in terms of possible contributing agents and in particular, the cultural traditions of the Greeks and their adjustment problems were highlighted. It was suggested that the stresses of cultural change and the socioeconomic pressures borne by the parents resulted in deprivation of their children who were also exposed to a confused language environment, and that a combination of these variables could lead to decompensation into an autistic state in an already vulnerable child."} {"id": "PMID:1272100", "title": "House dust mites and infant-use sheepskins.", "content": "A study of dust mite populations in infant-use lambskin and other bedding has showm more mites present in the latter. Regular vacuuming of the lambskin greatly reduces the mite population on it, but cannot prevent recolonization from adjacent areas.", "contents": "House dust mites and infant-use sheepskins. A study of dust mite populations in infant-use lambskin and other bedding has showm more mites present in the latter. Regular vacuuming of the lambskin greatly reduces the mite population on it, but cannot prevent recolonization from adjacent areas."} {"id": "PMID:1272101", "title": "Cor triatriatum.", "content": "A case of cortriatriatum, which is not included in three types of Loeffler's classification, is reported, and a complete description of the anatomy and pathology of the case is given. A successful surgical repair of this malformation is possible; therefore the importance of its recognition is emphasized. The clinical manifestations and the different aetiopathogenic theories are reviewed.", "contents": "Cor triatriatum. A case of cortriatriatum, which is not included in three types of Loeffler's classification, is reported, and a complete description of the anatomy and pathology of the case is given. A successful surgical repair of this malformation is possible; therefore the importance of its recognition is emphasized. The clinical manifestations and the different aetiopathogenic theories are reviewed."} {"id": "PMID:1272102", "title": "Renal calculi and their management.", "content": "Any patient presenting with renal colic requires the taking of a detailed history-- with inquiries about diet and drugs, an examination of the urine, intravenous pyelography and measurement of the calcium concentration in serum and urine. Any stone passed should be analysed. Recurrent stone formation warrants more comprehensive metabolic investigation. The cause of renal calculi in most patients is still not known. When a cause is found, specific treatment can prevent or control stone formation. For the majority in whom no abnormality is detected, various methods of reducing stone formation have been tried but results are disappointing. The most important points in management are the early detection and effective treatment of urinary tract infection or obstruction and the maintenance of a high fluid intake.", "contents": "Renal calculi and their management. Any patient presenting with renal colic requires the taking of a detailed history-- with inquiries about diet and drugs, an examination of the urine, intravenous pyelography and measurement of the calcium concentration in serum and urine. Any stone passed should be analysed. Recurrent stone formation warrants more comprehensive metabolic investigation. The cause of renal calculi in most patients is still not known. When a cause is found, specific treatment can prevent or control stone formation. For the majority in whom no abnormality is detected, various methods of reducing stone formation have been tried but results are disappointing. The most important points in management are the early detection and effective treatment of urinary tract infection or obstruction and the maintenance of a high fluid intake."} {"id": "PMID:1272103", "title": "Plasma drug concentrations in therapeutics.", "content": "The literature describing drugs assay in plasma and its value for optimal therapy for individual patients is expanding rapidly. The present review seeks to clarify the rationale underlying the assay of plasma concentrations of drugs, and it attempts to define principles for judging the likely value of assaying a particular drug. Examples are given of drugs which are being usefully measured in clinical practice. The most commonly used assay techniques are briefly described, and their principal advantages and limitations are indicated.", "contents": "Plasma drug concentrations in therapeutics. The literature describing drugs assay in plasma and its value for optimal therapy for individual patients is expanding rapidly. The present review seeks to clarify the rationale underlying the assay of plasma concentrations of drugs, and it attempts to define principles for judging the likely value of assaying a particular drug. Examples are given of drugs which are being usefully measured in clinical practice. The most commonly used assay techniques are briefly described, and their principal advantages and limitations are indicated."} {"id": "PMID:1272109", "title": "Occupational injuries: an exploratory analysis of successful Australian strategies.", "content": "An examination of occupational injuries in Australia during the 1960's is made. It is shown that the incidence of occupational injuries decreased by about 12% during the decade and that occupational injuries now approximate 200,000 per annum. Although there are approximately six injuries to men for every one to women,types and sites of occupational injury do not differ between the sexes. Occupational injuries occur most frequently on Mondays, and the incidence decreases sequentially during the week. The age distribution for serious injuries (incurring an absence from work of more than 28 days) differs markedly from the equivalent distributions for minor occupational and all road injuries in that the third, fourth, fifth, and sixth decades of life each contribute about 20% of this total. The customary heavy over-representation of young males is notably absent. \"Passive\" countermeasures (those that are behaviour-independent) are held to have been differentially more successful than those that are \"active\" (those that require active cooperation). Examples are given.", "contents": "Occupational injuries: an exploratory analysis of successful Australian strategies. An examination of occupational injuries in Australia during the 1960's is made. It is shown that the incidence of occupational injuries decreased by about 12% during the decade and that occupational injuries now approximate 200,000 per annum. Although there are approximately six injuries to men for every one to women,types and sites of occupational injury do not differ between the sexes. Occupational injuries occur most frequently on Mondays, and the incidence decreases sequentially during the week. The age distribution for serious injuries (incurring an absence from work of more than 28 days) differs markedly from the equivalent distributions for minor occupational and all road injuries in that the third, fourth, fifth, and sixth decades of life each contribute about 20% of this total. The customary heavy over-representation of young males is notably absent. \"Passive\" countermeasures (those that are behaviour-independent) are held to have been differentially more successful than those that are \"active\" (those that require active cooperation). Examples are given."} {"id": "PMID:1272110", "title": "Infection with Mycoplasma pneumoniae: clinical and serological data on 286 patients.", "content": "In a 14-month period from January, 1971, 286 patients, referred for investigation of a variety of illnesses, were found to have complement-fixing antibodies to Mycoplasma pneumoniae to a titre of 1:32 or greater. Clinical findings in these patients are presented in a form which relates them to different antibody levels. Patients with central nervous system disease are described in some detail and the occurence of rash, arthropathy and a variety of other syndromes is noted. The suggestion is made that low-titred M. pneumoniae antibody appears as an anamnestic response to infection with other agents.", "contents": "Infection with Mycoplasma pneumoniae: clinical and serological data on 286 patients. In a 14-month period from January, 1971, 286 patients, referred for investigation of a variety of illnesses, were found to have complement-fixing antibodies to Mycoplasma pneumoniae to a titre of 1:32 or greater. Clinical findings in these patients are presented in a form which relates them to different antibody levels. Patients with central nervous system disease are described in some detail and the occurence of rash, arthropathy and a variety of other syndromes is noted. The suggestion is made that low-titred M. pneumoniae antibody appears as an anamnestic response to infection with other agents."} {"id": "PMID:1272111", "title": "Cronkhite-Canada syndrome.", "content": "The first case in Australia of the rare Cronkhite-Canada syndrome which comprises generalized gastrointestinal polyposis, alopecia, onychatrophia and pigmentation, is described. The patient was initially treated for hypothyroidism, but subsequently developed protein-losing enteropathy and adenocarcinoma of the colon arising in the polyp.", "contents": "Cronkhite-Canada syndrome. The first case in Australia of the rare Cronkhite-Canada syndrome which comprises generalized gastrointestinal polyposis, alopecia, onychatrophia and pigmentation, is described. The patient was initially treated for hypothyroidism, but subsequently developed protein-losing enteropathy and adenocarcinoma of the colon arising in the polyp."} {"id": "PMID:1272112", "title": "An improved M.B., B.S., \"final\" examination in surgery.", "content": "A new final year examination in surgery has been devised. It consists of a clinical assessment made by a surgical tutor over a period of six weeks throughout a student's surgical term, a visual, clinically orientated written examination a \"spotter-type\" practical examination and a viva-voce examination. Correlation with students' previous performances has been good and the examination appears to have solved many of the problems which necessitated its development.", "contents": "An improved M.B., B.S., \"final\" examination in surgery. A new final year examination in surgery has been devised. It consists of a clinical assessment made by a surgical tutor over a period of six weeks throughout a student's surgical term, a visual, clinically orientated written examination a \"spotter-type\" practical examination and a viva-voce examination. Correlation with students' previous performances has been good and the examination appears to have solved many of the problems which necessitated its development."} {"id": "PMID:1272113", "title": "Severe measles in Vietnam.", "content": "The effects of measles epidemic amongst Cambodian refugees who were inadequately housed and fed in a refugee camp on the Cambodian-Vietnam border are described. As the condition of the people deteriorated, kwashiokor became prevalent and from a comparatively low death rate initially, children began to die in quick succession. With the supply of extra high-protein food this trend was soon reversed. However, the mortality figures given are official ones and there is no way of checking them by counting graves, as the Cambodians burn their dead. Therefore, it is more than likely that the real situation is understated.", "contents": "Severe measles in Vietnam. The effects of measles epidemic amongst Cambodian refugees who were inadequately housed and fed in a refugee camp on the Cambodian-Vietnam border are described. As the condition of the people deteriorated, kwashiokor became prevalent and from a comparatively low death rate initially, children began to die in quick succession. With the supply of extra high-protein food this trend was soon reversed. However, the mortality figures given are official ones and there is no way of checking them by counting graves, as the Cambodians burn their dead. Therefore, it is more than likely that the real situation is understated."} {"id": "PMID:1272119", "title": "Complications of amniocentesis.", "content": "A retrospective survey of 358 consecutive amniocenteses was undertaken. The incidence of failure was 37 (9.6%); most commonly this was due to oligohydramnios. A suprapubic tap was the most likely to be successful, but was accompanied by premature rupture of membranes in 3.8% of the cases. Spontaneous rupture of membranes, followed by delivery of a premature infant, occurred 15 times (4.2%). Blood-stained fluid was obtained on 47 occasions (13%), but, apart from the theoretical risks of fetomaternal haemorrhage and fetal exsanguination, and an association with maternal abdominal pain, there appeared to be no serious sequelae from this complication. Withdrawal of blood-stained fluid was not prevented by prior placental localization and was not related to the site of the tap. There were 14 perinatal deaths (equal to a rate of 50 per 1,000 births) and, although no fetal deaths could be directly attributed to amniocentesis, there were four cases in which the procedure could not be completely absolved. Three patients underwent emergency caesarean section because of severe abdominal pain after anmiocentesis. Two had amniotic fluid peritonism and the third had minor intraperitoneal bleeding. Amniocentesis is not without maternal and fetal complications and should be undertaken with due regard to the risks involved.", "contents": "Complications of amniocentesis. A retrospective survey of 358 consecutive amniocenteses was undertaken. The incidence of failure was 37 (9.6%); most commonly this was due to oligohydramnios. A suprapubic tap was the most likely to be successful, but was accompanied by premature rupture of membranes in 3.8% of the cases. Spontaneous rupture of membranes, followed by delivery of a premature infant, occurred 15 times (4.2%). Blood-stained fluid was obtained on 47 occasions (13%), but, apart from the theoretical risks of fetomaternal haemorrhage and fetal exsanguination, and an association with maternal abdominal pain, there appeared to be no serious sequelae from this complication. Withdrawal of blood-stained fluid was not prevented by prior placental localization and was not related to the site of the tap. There were 14 perinatal deaths (equal to a rate of 50 per 1,000 births) and, although no fetal deaths could be directly attributed to amniocentesis, there were four cases in which the procedure could not be completely absolved. Three patients underwent emergency caesarean section because of severe abdominal pain after anmiocentesis. Two had amniotic fluid peritonism and the third had minor intraperitoneal bleeding. Amniocentesis is not without maternal and fetal complications and should be undertaken with due regard to the risks involved."} {"id": "PMID:1272120", "title": "Mortality from asthma and bronchodilator aerosols.", "content": "The mortality rate from asthma in Australia had a transcient rise between 1960 to 1967. There was a remarkably high correlation between the sales of pressurized adrenergic aerosols in each of the four most populated States and the corresponding asthma mortality rate for two triennia, 1961 to 1963 and 1964 to 1966. This relationship was not found after 1966. From 1965 to 1966, Australians were warned repeatedly of the possible dangers of over-usage of the adrenergic aerosols. The sales pattern of the aerosols altered, showing a slackening of the rate of increase of sales in 1966 and 1967. This and other evidence suggests that the warnings may have reduced the prevalence of over-usage of the aerosols and that before this, over-usage of the adrenergic aerosols could have caused the epidemic of asthma deaths.", "contents": "Mortality from asthma and bronchodilator aerosols. The mortality rate from asthma in Australia had a transcient rise between 1960 to 1967. There was a remarkably high correlation between the sales of pressurized adrenergic aerosols in each of the four most populated States and the corresponding asthma mortality rate for two triennia, 1961 to 1963 and 1964 to 1966. This relationship was not found after 1966. From 1965 to 1966, Australians were warned repeatedly of the possible dangers of over-usage of the adrenergic aerosols. The sales pattern of the aerosols altered, showing a slackening of the rate of increase of sales in 1966 and 1967. This and other evidence suggests that the warnings may have reduced the prevalence of over-usage of the aerosols and that before this, over-usage of the adrenergic aerosols could have caused the epidemic of asthma deaths."} {"id": "PMID:1272121", "title": "An appraisal of the treatment of femoral shaft fracture: open versus closed.", "content": "Results of treatment of 103 femoral shaft fractures have been studied, the complications encountered are described and the final impression of the writer on the methodology of treatment is presented.", "contents": "An appraisal of the treatment of femoral shaft fracture: open versus closed. Results of treatment of 103 femoral shaft fractures have been studied, the complications encountered are described and the final impression of the writer on the methodology of treatment is presented."} {"id": "PMID:1272122", "title": "Six cases of severe head injury treated by exercise in addition to other therapies.", "content": "Six cases of severe head injury treated with vigorous early morning exercise in addition to more orthodox therapies are presented. Observations on behaviour and psychometric testing have been used to assess results. Discussion is centred round the benefits of early morning exercise.", "contents": "Six cases of severe head injury treated by exercise in addition to other therapies. Six cases of severe head injury treated with vigorous early morning exercise in addition to more orthodox therapies are presented. Observations on behaviour and psychometric testing have been used to assess results. Discussion is centred round the benefits of early morning exercise."} {"id": "PMID:1272123", "title": "Action of tilidine hydrochloride and morphine hydrochloride on ventilatory control in normal subjects.", "content": "The action of tilidine hydrochloride and morphine hydrochloride on the ventilatory response to inhaled carbon dioxide has been assessed in 10 normal volunteers. In doses of 50 mg and 100 mg given intravenously, tilidine hydrochloride induced less respiratory depression than 10 mg of morphine given intravenously. Side effects were not different or troublesome with either drug. Depending on its relative pain-relieving property, tilidine hydrochloride may have advantages over morphine as an analgesic.", "contents": "Action of tilidine hydrochloride and morphine hydrochloride on ventilatory control in normal subjects. The action of tilidine hydrochloride and morphine hydrochloride on the ventilatory response to inhaled carbon dioxide has been assessed in 10 normal volunteers. In doses of 50 mg and 100 mg given intravenously, tilidine hydrochloride induced less respiratory depression than 10 mg of morphine given intravenously. Side effects were not different or troublesome with either drug. Depending on its relative pain-relieving property, tilidine hydrochloride may have advantages over morphine as an analgesic."} {"id": "PMID:1272124", "title": "Hypertrophic colonic tuberculosis.", "content": "A patient who has suffered from hypertrophic colonic tuberculosis caused by the human strain of tubercule bacillus is presented. Despite being an uncommon presentation of tuberculosis, it is of more than academic interest to surgeons practising in tropical countries.", "contents": "Hypertrophic colonic tuberculosis. A patient who has suffered from hypertrophic colonic tuberculosis caused by the human strain of tubercule bacillus is presented. Despite being an uncommon presentation of tuberculosis, it is of more than academic interest to surgeons practising in tropical countries."} {"id": "PMID:1272125", "title": "Gout, uric acid and renal disease.", "content": "Gout may be associated with renal disease in two situations: (i) when the abnormal urate metabolism is the primary phenomenon and renal disease occurs secondary to this; or (ii) when the intrinsic renal disease is primary, and results in secondary abnormalities of renal function. Kidney damage secondary to gout is associated with urate deposits either in the intersitium as microtophi or as uric acid crystals within tubules, and vascular disease and infection are superimposed. Hyperuricaemia is a frequent sequel to parenchymal renal disease, but gouty arthritis develops only when the hyperuricaemia is unusually severe. Urate metabolism alters when renal excretion of urate is reduced. The management of these problems is discussed.", "contents": "Gout, uric acid and renal disease. Gout may be associated with renal disease in two situations: (i) when the abnormal urate metabolism is the primary phenomenon and renal disease occurs secondary to this; or (ii) when the intrinsic renal disease is primary, and results in secondary abnormalities of renal function. Kidney damage secondary to gout is associated with urate deposits either in the intersitium as microtophi or as uric acid crystals within tubules, and vascular disease and infection are superimposed. Hyperuricaemia is a frequent sequel to parenchymal renal disease, but gouty arthritis develops only when the hyperuricaemia is unusually severe. Urate metabolism alters when renal excretion of urate is reduced. The management of these problems is discussed."} {"id": "PMID:1272126", "title": "Spiders of the genus Loxosceles in Australia.", "content": "A previous report of the presence of loxoscelid spiders in Australia is confirmed by a further finding of Loxosceles rufescens at a second suburban locality in Adelaide, South Australia. There is thus a third genus of potentially lethal spiders in Australia.", "contents": "Spiders of the genus Loxosceles in Australia. A previous report of the presence of loxoscelid spiders in Australia is confirmed by a further finding of Loxosceles rufescens at a second suburban locality in Adelaide, South Australia. There is thus a third genus of potentially lethal spiders in Australia."} {"id": "PMID:1272136", "title": "Sudden death in infancy syndrome in Western Australia.", "content": "The objects of the Western Australian investigation into the sudden death in infancy syndrome are stated. Evidence is presented which suggests that these children are subject to an asphyxial mode of dying. It is postulated that anaphylaxis, due to hypersensitivity to the house dust mite, and possibly other allergens, is implicated, with the respiratory system as the target organ. A family counselling service is described.", "contents": "Sudden death in infancy syndrome in Western Australia. The objects of the Western Australian investigation into the sudden death in infancy syndrome are stated. Evidence is presented which suggests that these children are subject to an asphyxial mode of dying. It is postulated that anaphylaxis, due to hypersensitivity to the house dust mite, and possibly other allergens, is implicated, with the respiratory system as the target organ. A family counselling service is described."} {"id": "PMID:1272137", "title": "Bennett's fracture in general practice.", "content": "A review of eight cases of Bennett's fracture is presented. The mechanism of injury appears well defined and a simple method of treatment is described. Uniformly good results have been achieved in all eight cases.", "contents": "Bennett's fracture in general practice. A review of eight cases of Bennett's fracture is presented. The mechanism of injury appears well defined and a simple method of treatment is described. Uniformly good results have been achieved in all eight cases."} {"id": "PMID:1272138", "title": "Total blood lead levels in petrol vendors.", "content": "The total blood lead levels of a group of 48 petrol vendors and a comparison group of 47 clerks and students were determined. The mean total blood lead level of the petrol vendors was 32-9 mug/100 ml (S.E.1-73 mug/100 ml). The mean level of the comparison group was 14-3 mug/100 ml (S.E. 0-72 mug/100 ml). The concentrations of lead in the blood of petrol vendors were significantly higher than those of the comparison group, and seven individual values fell above the currently accepted \"level of concern\". Recent relevant literature is reviewed.", "contents": "Total blood lead levels in petrol vendors. The total blood lead levels of a group of 48 petrol vendors and a comparison group of 47 clerks and students were determined. The mean total blood lead level of the petrol vendors was 32-9 mug/100 ml (S.E.1-73 mug/100 ml). The mean level of the comparison group was 14-3 mug/100 ml (S.E. 0-72 mug/100 ml). The concentrations of lead in the blood of petrol vendors were significantly higher than those of the comparison group, and seven individual values fell above the currently accepted \"level of concern\". Recent relevant literature is reviewed."} {"id": "PMID:1272139", "title": "Disseminated intravascular thrombosis as the cause of ischaemic enterocolitis.", "content": "Disseminated intravascular thrombosis was diagnosed in a woman aged 63 years. At autopsy the typical appearances of ischaemic enterocolitis were found, together with thrombi in other organs. This case illustrates the previously postulated connection between intravascular thrombosis and ischaemic enterocolitis.", "contents": "Disseminated intravascular thrombosis as the cause of ischaemic enterocolitis. Disseminated intravascular thrombosis was diagnosed in a woman aged 63 years. At autopsy the typical appearances of ischaemic enterocolitis were found, together with thrombi in other organs. This case illustrates the previously postulated connection between intravascular thrombosis and ischaemic enterocolitis."} {"id": "PMID:1272141", "title": "Comparison of low doses of haloperidol and diazepam in anxiety states.", "content": "A clinical comparison was made between a butyrophenone drug (haloperidol), and an established antianxiety agent of the benzodiazepine group (diazepam). Both drugs were highly effective in reducing anxiety symptoms, with few and mild side effects of diminishing intensity throughout the trial period.", "contents": "Comparison of low doses of haloperidol and diazepam in anxiety states. A clinical comparison was made between a butyrophenone drug (haloperidol), and an established antianxiety agent of the benzodiazepine group (diazepam). Both drugs were highly effective in reducing anxiety symptoms, with few and mild side effects of diminishing intensity throughout the trial period."} {"id": "PMID:1272143", "title": "Solitary ulcer of the rectum, A report of fiteen cases.", "content": "Fifteen cases of solitary ulcer of the rectum are described. The patients complained mainly of rectal bleeding, discomfort and passage per rectum of mucus. The lesion is most commonly situated on the anterior wall of the rectum and can be red and granular, nodular or ulcerating. Peolapse was found in nine cases. The histological lesion is similar to that seen in rectal prolapse. The condition can be mistaken for colitis, adenomatous polyp or carcinoma. Reassurance, defaecation reeducation and dealing with the patients'emotional problems alleviated the condition in some cases. Surgery to remove a prolapsing segment was performed in one case only.", "contents": "Solitary ulcer of the rectum, A report of fiteen cases. Fifteen cases of solitary ulcer of the rectum are described. The patients complained mainly of rectal bleeding, discomfort and passage per rectum of mucus. The lesion is most commonly situated on the anterior wall of the rectum and can be red and granular, nodular or ulcerating. Peolapse was found in nine cases. The histological lesion is similar to that seen in rectal prolapse. The condition can be mistaken for colitis, adenomatous polyp or carcinoma. Reassurance, defaecation reeducation and dealing with the patients'emotional problems alleviated the condition in some cases. Surgery to remove a prolapsing segment was performed in one case only."} {"id": "PMID:1272144", "title": "Difficulties with the diagnosis of linitis plastica carcinoma of the rectum and anal canal.", "content": "The early and precise diagnosis of linitis plastica-type tumours of the rectum and anal canal is difficult because of their insidious presentation and anaplastic nature. A case report is documented of a patient with a linitis plastica tumour of the lower rectum and anal canal which arose as a secondary tumour from the prostate. The presentation, clinical features, treatment and pathological findings in this case are contrasted with those from other reported cases of prostatic carcinoma invading the rectum and of linitis plastica carcinoma of the large bowel. The unique features of the case are summarized.", "contents": "Difficulties with the diagnosis of linitis plastica carcinoma of the rectum and anal canal. The early and precise diagnosis of linitis plastica-type tumours of the rectum and anal canal is difficult because of their insidious presentation and anaplastic nature. A case report is documented of a patient with a linitis plastica tumour of the lower rectum and anal canal which arose as a secondary tumour from the prostate. The presentation, clinical features, treatment and pathological findings in this case are contrasted with those from other reported cases of prostatic carcinoma invading the rectum and of linitis plastica carcinoma of the large bowel. The unique features of the case are summarized."} {"id": "PMID:1272148", "title": "Antibody response to one and two doses of influenza virus subunit vaccine.", "content": "Antibody studies were undertaken to evaluate the responses after one and two-dose schedules of influenza immunization with subunit influenza vaccine. The responses were studied in two adult population groups after the administration of a vaccine containing the most recent epidemic strains A/Pt Chalmers/73 and B/Hong Kong/8/73. Responses to the A component of the vaccine were greater than those to the B strain. Patients with initially low antibody levels responded better than those with higher levels. There was little additional benefit from the second dose of vaccine.", "contents": "Antibody response to one and two doses of influenza virus subunit vaccine. Antibody studies were undertaken to evaluate the responses after one and two-dose schedules of influenza immunization with subunit influenza vaccine. The responses were studied in two adult population groups after the administration of a vaccine containing the most recent epidemic strains A/Pt Chalmers/73 and B/Hong Kong/8/73. Responses to the A component of the vaccine were greater than those to the B strain. Patients with initially low antibody levels responded better than those with higher levels. There was little additional benefit from the second dose of vaccine."} {"id": "PMID:1272149", "title": "Definition of an exercise tolerance test.", "content": "Three hundred subjects undertook a submaximal bicycle ergometry procedure which was terminated at level 19 on the Borg perceived exertion rating scale. The findings indicated that the total work output was an effective reference criterion for each individual. Age and height were considerably more dominant than weight in affecting this output in both sexes. In women, however, the use of the maximum work load/maximum systolic blood pressure ratio gave the best explanation of variation. A numerical relative fitness ranking derived from the work output was developed to achieve comparison among subjects irrespective of age, height, weight and sex. This categorization revealed, interalia, that the average maximum systolic blood pressure was a major limiting factor in performance. Significant changes characteristic of ischaemia occurred in the electrocardiograms of a substantial proportion of subjects, including the apparently well, the proportion being higher in women than in men. There were definite differences between the ranked work load categories. The relative fitness ranking is of value in assessing a variety of factors affecting performance in heterogeneous populations, and also in following population responses to various procedures.", "contents": "Definition of an exercise tolerance test. Three hundred subjects undertook a submaximal bicycle ergometry procedure which was terminated at level 19 on the Borg perceived exertion rating scale. The findings indicated that the total work output was an effective reference criterion for each individual. Age and height were considerably more dominant than weight in affecting this output in both sexes. In women, however, the use of the maximum work load/maximum systolic blood pressure ratio gave the best explanation of variation. A numerical relative fitness ranking derived from the work output was developed to achieve comparison among subjects irrespective of age, height, weight and sex. This categorization revealed, interalia, that the average maximum systolic blood pressure was a major limiting factor in performance. Significant changes characteristic of ischaemia occurred in the electrocardiograms of a substantial proportion of subjects, including the apparently well, the proportion being higher in women than in men. There were definite differences between the ranked work load categories. The relative fitness ranking is of value in assessing a variety of factors affecting performance in heterogeneous populations, and also in following population responses to various procedures."} {"id": "PMID:1272160", "title": "Lithium carbonate and hypothyroidism.", "content": "A case of hypothyroidism as a complication of lithium maintenance therapy is reported. Clinicians should be aware of this condition and patients receiving long-term lithium maintenance therapy should have their thyroid gland function assessed periodically.", "contents": "Lithium carbonate and hypothyroidism. A case of hypothyroidism as a complication of lithium maintenance therapy is reported. Clinicians should be aware of this condition and patients receiving long-term lithium maintenance therapy should have their thyroid gland function assessed periodically."} {"id": "PMID:1272161", "title": "St. Agnes: a study of a health centre in evolution.", "content": "The growth of St Agnes Health Centre is described, with its transition from simple group practice to a comprehensive health centre over a five-year period. Its position in a rapidly growing suburb is analysed and illustrated by usage and referral patterns. The sucessful integration of general practice, sessional specialists and allied health workers under one roof makes it unique as a primary health care project in Australia.", "contents": "St. Agnes: a study of a health centre in evolution. The growth of St Agnes Health Centre is described, with its transition from simple group practice to a comprehensive health centre over a five-year period. Its position in a rapidly growing suburb is analysed and illustrated by usage and referral patterns. The sucessful integration of general practice, sessional specialists and allied health workers under one roof makes it unique as a primary health care project in Australia."} {"id": "PMID:1272168", "title": "[CSF-evaluation in unilateral, bilateral and alternant facial paralysis (author's transl)].", "content": "Etiology of idiopathic facial paralysis remains mostly unknown because further investigations seem unnecessary being the only symptom. Differentiated evaluation of CSF however for cytological or proteinous abnormalities should be performed aside serological examinations. In 9 patients treated within 8 months in our hospital diagnosis could be made by these procedures. Inflammation, if cause of facial paralysis, can only call pleocytosis, if localised within or next to the leptomeninges; protein of CSF perhaps will increase, if local inflammation of the nerve is more distant to subarachnoid space. \"Idiopathic facial paralysis\" however will not exclude focal inflammation far from subarachnoid space. Surgical decompression should not be performed without previous examination of CSF in regard of it's uncertain success.", "contents": "[CSF-evaluation in unilateral, bilateral and alternant facial paralysis (author's transl)]. Etiology of idiopathic facial paralysis remains mostly unknown because further investigations seem unnecessary being the only symptom. Differentiated evaluation of CSF however for cytological or proteinous abnormalities should be performed aside serological examinations. In 9 patients treated within 8 months in our hospital diagnosis could be made by these procedures. Inflammation, if cause of facial paralysis, can only call pleocytosis, if localised within or next to the leptomeninges; protein of CSF perhaps will increase, if local inflammation of the nerve is more distant to subarachnoid space. \"Idiopathic facial paralysis\" however will not exclude focal inflammation far from subarachnoid space. Surgical decompression should not be performed without previous examination of CSF in regard of it's uncertain success."} {"id": "PMID:1272169", "title": "[Distraneurin:not a therapeutic agent against alcoholism (author's transl)].", "content": "This notice shall inform general practitioners, that Distraneurin (Chlormethiazol) - beside of being a very successful drug in treating delirium tremens, suppressing withdrawals and therefore helping alcoholics by their attempt to get abstinent - bears a great danger of iatrogenic habit formation, when it is prescribed continuously over more than three weeks. The patient describes the effect of Distraneurin in the same way as the effect of alcoholconsume, wishes tenacious to extend the order of this drug and elevates the dose and gets addicted to it.", "contents": "[Distraneurin:not a therapeutic agent against alcoholism (author's transl)]. This notice shall inform general practitioners, that Distraneurin (Chlormethiazol) - beside of being a very successful drug in treating delirium tremens, suppressing withdrawals and therefore helping alcoholics by their attempt to get abstinent - bears a great danger of iatrogenic habit formation, when it is prescribed continuously over more than three weeks. The patient describes the effect of Distraneurin in the same way as the effect of alcoholconsume, wishes tenacious to extend the order of this drug and elevates the dose and gets addicted to it."} {"id": "PMID:1272170", "title": "[Reduction of smoking hazards by Denicotea filter-cartridges (author's transl)].", "content": "In the present study the efficiency of Denicotea filter-cartridges is determined as indicated by change of heart rate, skin temperature, urinary nicotine-content and subjective symptoms. Compared with standard smoking effects the use of Denicotea filters produces smaller increases in heart rate and significant reductions of urinary nicotine-content. The majority of the probands no longer experienced side effects. Thus, the elimination of nicotine from smoke by Denicotea filters is effectively demonstrated. Because only a minority of smokers is actually willing to discontinue their habit, despite medical advice, the introduction of Denicotea filters presents itself as a useful alternative.", "contents": "[Reduction of smoking hazards by Denicotea filter-cartridges (author's transl)]. In the present study the efficiency of Denicotea filter-cartridges is determined as indicated by change of heart rate, skin temperature, urinary nicotine-content and subjective symptoms. Compared with standard smoking effects the use of Denicotea filters produces smaller increases in heart rate and significant reductions of urinary nicotine-content. The majority of the probands no longer experienced side effects. Thus, the elimination of nicotine from smoke by Denicotea filters is effectively demonstrated. Because only a minority of smokers is actually willing to discontinue their habit, despite medical advice, the introduction of Denicotea filters presents itself as a useful alternative."} {"id": "PMID:1272173", "title": "[Investigation with the MMPI saarbr\u00fccken in patients with ulcerative colitis (author's transl)].", "content": "The aim of our investigation was to establish whether certain personality traits of patients with ulcerative colitis could be subjected to verification by means of a controlled psychological test. 30 patients with ulcerative colitis and 30 \"healthy\" control persons were tested with the MMPI Saarbr\u00fccken. The colitis patients differed from the control persons in respect of their significantly higher scores on the hypochondria scale, the depression scale, the paranoia scale and the scale measuring social introversion. These higher scores proved to be independent of duration of illness. On the other scales there were no significant differences.", "contents": "[Investigation with the MMPI saarbr\u00fccken in patients with ulcerative colitis (author's transl)]. The aim of our investigation was to establish whether certain personality traits of patients with ulcerative colitis could be subjected to verification by means of a controlled psychological test. 30 patients with ulcerative colitis and 30 \"healthy\" control persons were tested with the MMPI Saarbr\u00fccken. The colitis patients differed from the control persons in respect of their significantly higher scores on the hypochondria scale, the depression scale, the paranoia scale and the scale measuring social introversion. These higher scores proved to be independent of duration of illness. On the other scales there were no significant differences."} {"id": "PMID:1272174", "title": "[Rare fistulation in enterocolitis regionalis (Crohn's disease) (author's transl)].", "content": "The transmural inflammation in Crohn's disease, the variable localization of the disease and the tendency to a descending spread, all lead to a multitude of possible fistulae, the presence of which is often difficult to demonstrate. This is a report on 5 unusual fistula systems: in 2 cases entero-enteral (one of which with hydronephrosis), 1 case of rectovaginal fistula, 1 case of a branched fistula system in the right buttock, 1 case of fistulae between an abscess system in the spleen \"bed\" and the greater curvature of the stomach. A radiological and endoscopic diagnosis is important since surgically opened fistula systems heal only with great difficulty or not at all.", "contents": "[Rare fistulation in enterocolitis regionalis (Crohn's disease) (author's transl)]. The transmural inflammation in Crohn's disease, the variable localization of the disease and the tendency to a descending spread, all lead to a multitude of possible fistulae, the presence of which is often difficult to demonstrate. This is a report on 5 unusual fistula systems: in 2 cases entero-enteral (one of which with hydronephrosis), 1 case of rectovaginal fistula, 1 case of a branched fistula system in the right buttock, 1 case of fistulae between an abscess system in the spleen \"bed\" and the greater curvature of the stomach. A radiological and endoscopic diagnosis is important since surgically opened fistula systems heal only with great difficulty or not at all."} {"id": "PMID:1272177", "title": "[Spinal cord ischemia (syndrome of the sulcocommisural artery) after oral contraception for seven years (author's transl)].", "content": "The pathological history of an 29 years old woman with a partial subacute Brown Sequard syndrome traced to a closure of the right sulcocommisural artery in the Th IX area is described. The disease developed after oral contraception for seven years. The relations to the use of oral contraceptives are briefly discussed.", "contents": "[Spinal cord ischemia (syndrome of the sulcocommisural artery) after oral contraception for seven years (author's transl)]. The pathological history of an 29 years old woman with a partial subacute Brown Sequard syndrome traced to a closure of the right sulcocommisural artery in the Th IX area is described. The disease developed after oral contraception for seven years. The relations to the use of oral contraceptives are briefly discussed."} {"id": "PMID:1272178", "title": "[Indications and results of cerclage in cervical incompetence (author's transl)].", "content": "The results of 79 cerclage operations in gestation are reported. The rate of abortion increased in cases of more severe symptomatics: firstly, without labour and bleeding: 83 p.c. successful operations; secondly, with labour: 77 p.c.; thirdly, bleeding and without labour: 70p.c.; and lastly, with labour and bleeding: 40p.c. Before treatment with tocolytic pharmaca was possible, the period of gestation time could not successfully be prolonged if labour had started. With tocolytic pharmaca 56p.c. patients of this group gave birth to a living child. The rate of premature children was 23p.c. Cerclage operations were most successful after the 25th week of gestation. When applied before the 16th week of gestation, the success rate was below 69p.c. Treatment with tocolytic pharmaca increased the indication for cerclage operations. Cerclage operations together with tocolytic treatment are indicated in cases where labour and bleeding occur in gestation.", "contents": "[Indications and results of cerclage in cervical incompetence (author's transl)]. The results of 79 cerclage operations in gestation are reported. The rate of abortion increased in cases of more severe symptomatics: firstly, without labour and bleeding: 83 p.c. successful operations; secondly, with labour: 77 p.c.; thirdly, bleeding and without labour: 70p.c.; and lastly, with labour and bleeding: 40p.c. Before treatment with tocolytic pharmaca was possible, the period of gestation time could not successfully be prolonged if labour had started. With tocolytic pharmaca 56p.c. patients of this group gave birth to a living child. The rate of premature children was 23p.c. Cerclage operations were most successful after the 25th week of gestation. When applied before the 16th week of gestation, the success rate was below 69p.c. Treatment with tocolytic pharmaca increased the indication for cerclage operations. Cerclage operations together with tocolytic treatment are indicated in cases where labour and bleeding occur in gestation."} {"id": "PMID:1272179", "title": "[Secondary sterility following cesarean section (author's transl)].", "content": "In 98 patients with cesarean section secondary sterility was studied and compared with spontaneous labor in a control group. The rate of secondary sterility in the first group was 48,9% and there was no relation to the age. 25% of the women prevented pregnancy on account of maieusiophobia. Involuntary sterility was found in 29,2% and there was no relationship between secondary sterility and puerperalism.", "contents": "[Secondary sterility following cesarean section (author's transl)]. In 98 patients with cesarean section secondary sterility was studied and compared with spontaneous labor in a control group. The rate of secondary sterility in the first group was 48,9% and there was no relation to the age. 25% of the women prevented pregnancy on account of maieusiophobia. Involuntary sterility was found in 29,2% and there was no relationship between secondary sterility and puerperalism."} {"id": "PMID:1272180", "title": "[Mycoplasms in tumors of patients with carcinomata of the collum and its preliminary stages (author's transl)].", "content": "Within one year smears were taken from 190 patients who had not been pretreated in our oncological department. The culture media established were examined with regard to Mycoplasms. A Mycoplasma population was stated in 27 women. In the cases of carcinomata of the collum and in its preliminary stages, Mycoplasma infestation was about twice as frequent as in all other cases of genital carcinomata. Discussion is made if Mycoplasms are possible or promoting factors during the development of carcinomata of the collum.", "contents": "[Mycoplasms in tumors of patients with carcinomata of the collum and its preliminary stages (author's transl)]. Within one year smears were taken from 190 patients who had not been pretreated in our oncological department. The culture media established were examined with regard to Mycoplasms. A Mycoplasma population was stated in 27 women. In the cases of carcinomata of the collum and in its preliminary stages, Mycoplasma infestation was about twice as frequent as in all other cases of genital carcinomata. Discussion is made if Mycoplasms are possible or promoting factors during the development of carcinomata of the collum."} {"id": "PMID:1272244", "title": "Genetic analysis of antisuppressor mutants in the fission yeast Schizosaccharomyces pombe.", "content": "Fourteen unlinked sin genes could be mutated to recessive antisuppressor alleles preventing the expression of suppressors in the fission yeast Schizosaccharomyces pombe. cyh1 alleles, resistant to the ribosomal inhibitor cycloheximide, also have some antisuppressor effect. The genetical and physiological characterization of these mutants is consistent with the hypothesis that they affect components of the messenger RNA translation machinery such as tRNA modifying enzymes or ribosomal proteins.", "contents": "Genetic analysis of antisuppressor mutants in the fission yeast Schizosaccharomyces pombe. Fourteen unlinked sin genes could be mutated to recessive antisuppressor alleles preventing the expression of suppressors in the fission yeast Schizosaccharomyces pombe. cyh1 alleles, resistant to the ribosomal inhibitor cycloheximide, also have some antisuppressor effect. The genetical and physiological characterization of these mutants is consistent with the hypothesis that they affect components of the messenger RNA translation machinery such as tRNA modifying enzymes or ribosomal proteins."} {"id": "PMID:1272245", "title": "Molecular weight distribution of ribosomal proteins from several vertebrate species.", "content": "Two-dimensional polyacrylamide gel electrophoresis of proteins from the separated ribosomal subunits of rabbit reticulocytes, rabbit liver, mouse liver, rat liver, chicken liver, and toad liver was performed using the \"pH 4.5/SDS\" system previously described (Martini and Gould, 1975), with internal standards to measure the molecular weight distributions. With few exceptions, the patterns were remarkably similar, indicating a high degree of conservation during evolution of both net charge (largely determining mobility in the first dimension) and size (determining mobility in the second dimension). The aggregate mass (sum of molecular weights) of both small and large subunit proteins, about 0.65 X 10(6) and 0.95 X 10(6) daltons respectively, were invariant. These figures are significantly smaller than the hydrodynamically determined mass of protein in the subunits. The implications of this discrepancy, which is opposite that found in the prokaryotes, is discussed.", "contents": "Molecular weight distribution of ribosomal proteins from several vertebrate species. Two-dimensional polyacrylamide gel electrophoresis of proteins from the separated ribosomal subunits of rabbit reticulocytes, rabbit liver, mouse liver, rat liver, chicken liver, and toad liver was performed using the \"pH 4.5/SDS\" system previously described (Martini and Gould, 1975), with internal standards to measure the molecular weight distributions. With few exceptions, the patterns were remarkably similar, indicating a high degree of conservation during evolution of both net charge (largely determining mobility in the first dimension) and size (determining mobility in the second dimension). The aggregate mass (sum of molecular weights) of both small and large subunit proteins, about 0.65 X 10(6) and 0.95 X 10(6) daltons respectively, were invariant. These figures are significantly smaller than the hydrodynamically determined mass of protein in the subunits. The implications of this discrepancy, which is opposite that found in the prokaryotes, is discussed."} {"id": "PMID:1272246", "title": "Regulation of proteolytic enzymes in Podospora anserina: selection and properties of self-lysing mutant strains.", "content": "Previous results showed that cell disintegration in the fungus Podospora anserina occured through the action of two proteases, enzymes whose messengers were normally latent during the extension stage of the thallus. We selected three mutant strains in which the constitutive activity of the protease messengers was expressed by an arrest of growth early in development (10 to 30 hours after spore germination) and a reaction of cell disintegration, in the thallus, suppressible with beta-phenyl pyruvic acid, a protease inhibitor. The mutant character is recessive in one strain. In the case of the two strains in which the mutant trait is dominant, reversion studies have revealed that the deregulation resulted from the specific interaction between two genes and we have succeded in creating two non allelic incompatibility systems comparable to the non allelic gene interactions responsible for the incompatibility phenomena found between wild type races. We know, on the whole, that 11 loci are involved in the regulation of the proteases: five were revealed as incompatibility loci and six were discovered from investigations on four self-lysing mutant strains. It is suspected that all these genes act at the post-transcriptionnal level of the synthesis of specific proteolytic enzymes. We propose that the products of two genes act as \"repressors\" to prevent the protease messengers from being constitutively translated and that the products of the nine remaining genes exert a positive control by inducing translation, at the appropriate time, through the action of effectors resulting from specific interloci cooperation.", "contents": "Regulation of proteolytic enzymes in Podospora anserina: selection and properties of self-lysing mutant strains. Previous results showed that cell disintegration in the fungus Podospora anserina occured through the action of two proteases, enzymes whose messengers were normally latent during the extension stage of the thallus. We selected three mutant strains in which the constitutive activity of the protease messengers was expressed by an arrest of growth early in development (10 to 30 hours after spore germination) and a reaction of cell disintegration, in the thallus, suppressible with beta-phenyl pyruvic acid, a protease inhibitor. The mutant character is recessive in one strain. In the case of the two strains in which the mutant trait is dominant, reversion studies have revealed that the deregulation resulted from the specific interaction between two genes and we have succeded in creating two non allelic incompatibility systems comparable to the non allelic gene interactions responsible for the incompatibility phenomena found between wild type races. We know, on the whole, that 11 loci are involved in the regulation of the proteases: five were revealed as incompatibility loci and six were discovered from investigations on four self-lysing mutant strains. It is suspected that all these genes act at the post-transcriptionnal level of the synthesis of specific proteolytic enzymes. We propose that the products of two genes act as \"repressors\" to prevent the protease messengers from being constitutively translated and that the products of the nine remaining genes exert a positive control by inducing translation, at the appropriate time, through the action of effectors resulting from specific interloci cooperation."} {"id": "PMID:1272247", "title": "Surface topography of the Bacillus stearothermophilus ribosome.", "content": "The surface topography of the intact 70S ribosomes and free 30S and 50S subunits from Bacillus stearothermophilus strain 2184 was investigated by lactoperoxidase-catalyzed iodination. Two-dimensional polyacrylamide gel electrophoresis was employed to separate ribosomal proteins for analysis of their reactivity. Free 50S subunits incorporated about 18% more 125I than did 50S subunits derived from 70S ribosomes, whereas, free 30S subunits and 30S subunits derived from 70S ribosomes incorporated similar amounts of 125I. Iodinated 70S ribosomes and subunits retained 62-78% of the protein synthesis activity of untreated particles and sedimentation profiles showed no gross conformational changes due to iodination. The proteins most reactive to enzymatic iodination were S4, S7, S10 and Sa of the small subunit and L2, L4, L5/9, L6 and L36 of the large subunit. Proteins S2, S3, S7, S13, Sa, L5/9, L10, L11 and L24/25 were labeled substantially more in the free subunits than in the 70S ribosome. Other proteins, including S5, S9, S12, S15/16, S18 and L36 were more extensively iodinated in the 70S ribosomes than in the free subunits. The locations of tyrosine residues in some homologous ribosomal proteins from B. stearothermophilus and E. coli are compared.", "contents": "Surface topography of the Bacillus stearothermophilus ribosome. The surface topography of the intact 70S ribosomes and free 30S and 50S subunits from Bacillus stearothermophilus strain 2184 was investigated by lactoperoxidase-catalyzed iodination. Two-dimensional polyacrylamide gel electrophoresis was employed to separate ribosomal proteins for analysis of their reactivity. Free 50S subunits incorporated about 18% more 125I than did 50S subunits derived from 70S ribosomes, whereas, free 30S subunits and 30S subunits derived from 70S ribosomes incorporated similar amounts of 125I. Iodinated 70S ribosomes and subunits retained 62-78% of the protein synthesis activity of untreated particles and sedimentation profiles showed no gross conformational changes due to iodination. The proteins most reactive to enzymatic iodination were S4, S7, S10 and Sa of the small subunit and L2, L4, L5/9, L6 and L36 of the large subunit. Proteins S2, S3, S7, S13, Sa, L5/9, L10, L11 and L24/25 were labeled substantially more in the free subunits than in the 70S ribosome. Other proteins, including S5, S9, S12, S15/16, S18 and L36 were more extensively iodinated in the 70S ribosomes than in the free subunits. The locations of tyrosine residues in some homologous ribosomal proteins from B. stearothermophilus and E. coli are compared."} {"id": "PMID:1272248", "title": "Supra-operonic clustering of genes specifying glucose dissimilation in Pseudomonas putida.", "content": "The linkage arrangements of genes governing glucolysis in Pseudomonas putida have been determined by transductional analysis. Five genes (gdh, kgtA, kgtB, edd and eda), comprising at least three operons, are contransducible with each other, but not with ggu (glucose and gluconate uptake) nor with genes of a known supra-operonic cluster of genes specifying enzymes of other dissimilatory pathways, nor with a biochemically uncharacterized his marker. It thus appears that P. putida may have more than one chromosomal region in which genes with dissimilatory function are clustered in a supro-operonic fashion.", "contents": "Supra-operonic clustering of genes specifying glucose dissimilation in Pseudomonas putida. The linkage arrangements of genes governing glucolysis in Pseudomonas putida have been determined by transductional analysis. Five genes (gdh, kgtA, kgtB, edd and eda), comprising at least three operons, are contransducible with each other, but not with ggu (glucose and gluconate uptake) nor with genes of a known supra-operonic cluster of genes specifying enzymes of other dissimilatory pathways, nor with a biochemically uncharacterized his marker. It thus appears that P. putida may have more than one chromosomal region in which genes with dissimilatory function are clustered in a supro-operonic fashion."} {"id": "PMID:1272249", "title": "Effect of protein synthesis inhibition on recovery of UV- and gamma-irridated Schizosaccharomyces pombe from repair inhibition by caffeine.", "content": "The progress of repair in Schizosaccharomyces pombe may be followed during post-irradiation incubation by measuring, after various intervals, the ability of UV- or gamma-irradiated cells to avoid enhanced lethality when exposed to the repair inhibitor caffeine (Gentner and Werner, 1975). This technique has now been used to investigate the effect of inhibition of protein synthesis on repair of UV- and gamma-irradiation-induced damage in this organism. When protein synthesis was inhibited with cycloheximide in UV-irradiated wild-type cells, only a small amount of recovery from caffeine inhibition occurred; this indicated that post-irradiation protein synthesis was required for repair, and in particular for the recombinational repair pathway, which is a major mechanism for repair of UV damage in this organism. In gamma-irradiated wild-type cells, inhibition of post-irradiation protein synthesis reduced the rate of recovery from repair inhibition by caffeine, but full recovery from caffeine-sensitive damage did occur at longer incubation times. We attribute the reduction in rate to the effect of protein synthesis inhibition on the recombinational repair pathway, because this pathway is known to be involved in the repair of both gamma-ray and UV damage. The recovery that took place at the slower rate must reflect a caffeine-sensitive pathway which is involved only in repair of gamma-ray damage and which does not require post-irradiation protein synthesis for activity.", "contents": "Effect of protein synthesis inhibition on recovery of UV- and gamma-irridated Schizosaccharomyces pombe from repair inhibition by caffeine. The progress of repair in Schizosaccharomyces pombe may be followed during post-irradiation incubation by measuring, after various intervals, the ability of UV- or gamma-irradiated cells to avoid enhanced lethality when exposed to the repair inhibitor caffeine (Gentner and Werner, 1975). This technique has now been used to investigate the effect of inhibition of protein synthesis on repair of UV- and gamma-irradiation-induced damage in this organism. When protein synthesis was inhibited with cycloheximide in UV-irradiated wild-type cells, only a small amount of recovery from caffeine inhibition occurred; this indicated that post-irradiation protein synthesis was required for repair, and in particular for the recombinational repair pathway, which is a major mechanism for repair of UV damage in this organism. In gamma-irradiated wild-type cells, inhibition of post-irradiation protein synthesis reduced the rate of recovery from repair inhibition by caffeine, but full recovery from caffeine-sensitive damage did occur at longer incubation times. We attribute the reduction in rate to the effect of protein synthesis inhibition on the recombinational repair pathway, because this pathway is known to be involved in the repair of both gamma-ray and UV damage. The recovery that took place at the slower rate must reflect a caffeine-sensitive pathway which is involved only in repair of gamma-ray damage and which does not require post-irradiation protein synthesis for activity."} {"id": "PMID:1272250", "title": "Gene controlled selection of mitochondria in Paramecium.", "content": "The slow growing mutant cl1 of Paramecium, previously described (Sainsard, Claisse and Balmefrezol, 1974) differs from wild-type by a single recessive nuclear mutation and by a particular mitonchondrial phenotype (Mcl) that gene cl1 distinguishes from the wild-type mitochondrial phenotype (M+). A further analysis of these nucleo-mitochondrial interactions was carried out by confronting the genes cl1 and cl)+ with mixed populations of M+ and Mcl mitochondria obtained after cytoplasmic exchange at conjugation. The following results were obtained: 1. M+ and Mcl mitochondria introduced respectively into mutant and wild-type cells do not multiply easily; 2. when a mixed population (M+ + Mcl) is established, both mitochondrial types are maintained during the growth of the F1 heterozygous cl1/cl1+ clones; 3. when the nuclear segregation occurs in F2, the formation of homozygotes cl1/cl1 or cl1+/cl1+ is soon followed by the segregation of the two mitochondrial types, Mcl or M+, reconstituting the two parental nucleo-mitochondrial associations.", "contents": "Gene controlled selection of mitochondria in Paramecium. The slow growing mutant cl1 of Paramecium, previously described (Sainsard, Claisse and Balmefrezol, 1974) differs from wild-type by a single recessive nuclear mutation and by a particular mitonchondrial phenotype (Mcl) that gene cl1 distinguishes from the wild-type mitochondrial phenotype (M+). A further analysis of these nucleo-mitochondrial interactions was carried out by confronting the genes cl1 and cl)+ with mixed populations of M+ and Mcl mitochondria obtained after cytoplasmic exchange at conjugation. The following results were obtained: 1. M+ and Mcl mitochondria introduced respectively into mutant and wild-type cells do not multiply easily; 2. when a mixed population (M+ + Mcl) is established, both mitochondrial types are maintained during the growth of the F1 heterozygous cl1/cl1+ clones; 3. when the nuclear segregation occurs in F2, the formation of homozygotes cl1/cl1 or cl1+/cl1+ is soon followed by the segregation of the two mitochondrial types, Mcl or M+, reconstituting the two parental nucleo-mitochondrial associations."} {"id": "PMID:1272251", "title": "Biogenesis of mitochondria 44. comparative studies and mapping of mitochondrial oligomycin resistance mutations in yeast based on gene recombination and petite deletion analysis.", "content": "A comparative study of eight independently isolated mitochondrial oligomycin resistant mutants obtained from three laboratories show a variety of phenotypes based on cross resistance to venturicidin and sensitivity to low temperature. Analysis of recombination between pairs of markers indicate the existence of at least three genetic classes; class A, cross resistant to venturicidin and including the mutations OIII, [olil-r], [olgi-R], [tso-r]; class B, mutations OI, [olil7-r], [OLG2-R]; and class C, the mutation O11. The recombination data is consistent with mutations of each class residing in three separate genes, although mutations of class A and B show very close linkage. Recombination in non-polar crosses had demonstrated that markers of all three classes are linked to the mikl locus in the configuration (AB)-mikl-C. The mapping of this segment with respect to other markers of the mitochondrial genome and the order of classes A and B was established by analysis of co-retention frequenceis of markers in primary petite isolates as well as by analysis of marker overlap of genetically and physically defined petite genomes. The unambiguous order eryl-A-B-mik1-C-par was obtained. DNA-DNA hybridization studies using mtDNA isolated from selected petites confirms this map and estimates the physical separation of markers. A resonable correlation exists in this region of th genome between distances estimated physically by hybridization and genetically by frequencey of recombination in non-polar crosses. It is potulated that the oligomycin-mikamycin linkage group represents a cluster of genes involved in determing a number of mitochondrial membrane proteins associated with the mitochondrial ATPase and respiratory complex III.", "contents": "Biogenesis of mitochondria 44. comparative studies and mapping of mitochondrial oligomycin resistance mutations in yeast based on gene recombination and petite deletion analysis. A comparative study of eight independently isolated mitochondrial oligomycin resistant mutants obtained from three laboratories show a variety of phenotypes based on cross resistance to venturicidin and sensitivity to low temperature. Analysis of recombination between pairs of markers indicate the existence of at least three genetic classes; class A, cross resistant to venturicidin and including the mutations OIII, [olil-r], [olgi-R], [tso-r]; class B, mutations OI, [olil7-r], [OLG2-R]; and class C, the mutation O11. The recombination data is consistent with mutations of each class residing in three separate genes, although mutations of class A and B show very close linkage. Recombination in non-polar crosses had demonstrated that markers of all three classes are linked to the mikl locus in the configuration (AB)-mikl-C. The mapping of this segment with respect to other markers of the mitochondrial genome and the order of classes A and B was established by analysis of co-retention frequenceis of markers in primary petite isolates as well as by analysis of marker overlap of genetically and physically defined petite genomes. The unambiguous order eryl-A-B-mik1-C-par was obtained. DNA-DNA hybridization studies using mtDNA isolated from selected petites confirms this map and estimates the physical separation of markers. A resonable correlation exists in this region of th genome between distances estimated physically by hybridization and genetically by frequencey of recombination in non-polar crosses. It is potulated that the oligomycin-mikamycin linkage group represents a cluster of genes involved in determing a number of mitochondrial membrane proteins associated with the mitochondrial ATPase and respiratory complex III."} {"id": "PMID:1272253", "title": "Regulation of the D-glucose transport system in isolated fat cells.", "content": "Recent technical advances have yielded considerable new biochemical insights into the hexose transport systems of both brown and white fat cells. In the present studies a novel filtration method was used to monitor initial rates of 3-O-(3H)methylglucose uptake in isolated white fat cells. Transport of 3-O-methylglucose, a non-metabolizable analogue of glucose, occurred by facilitated diffusion, was inhibited by glucose, phloridzin, cytochalasin B and dipyridamole, and was rapidly stimulated by insulin as well as lectins. Total 3-O-methylglucose uptake in white fat cells could be attributed to two kinetically distinct processes in addition to a certain degree of diffusion. Two important new features of glucose transport in fat cells have been discovered. First, in both brown and white fat cells transport per se does not appear to be necessarily rate-limiting for further glucose metabolism. Thus vitamin K5, which markedly increases glucose oxidation by brown fat cells, did not affect the glucose transport system activity. Glucose utilization can apparently be significantly enhanced in fat cells by agents which either increase transport system activity or intracellular enzyme activity. Second, the transport system itself, whether in the basal state or after activation by insulin, lectins, or oxidants, is resistant to sulfhydryl reagents such as N-ethylmaleimide, while the increase in transport activity due to these agents is exquisitely sensitive to sulfhydryl blockage. N-ethylmaleimide blocks the stimulatory effect of insulin on transport whereas addition of insulin to fat cells prior to the reagent completely protects against this inhibitory effect. Further, N-ethylmaleimide prevents the elevated rates of transport system activity due to insulin (or other agents) from returning to basal levels once the cells are washed free of hormone. These data are consistent with the concept that activation of the transport system involves oxidation of key membrane sulfhydryls to the disulfide form, but alternative models are also possible. In any case, these findings provide a possible biochemical clue for future studies designed to identify the specific component(s) involved in the regulatory mechanism which modulates transport of glucose in isolated fat cells.", "contents": "Regulation of the D-glucose transport system in isolated fat cells. Recent technical advances have yielded considerable new biochemical insights into the hexose transport systems of both brown and white fat cells. In the present studies a novel filtration method was used to monitor initial rates of 3-O-(3H)methylglucose uptake in isolated white fat cells. Transport of 3-O-methylglucose, a non-metabolizable analogue of glucose, occurred by facilitated diffusion, was inhibited by glucose, phloridzin, cytochalasin B and dipyridamole, and was rapidly stimulated by insulin as well as lectins. Total 3-O-methylglucose uptake in white fat cells could be attributed to two kinetically distinct processes in addition to a certain degree of diffusion. Two important new features of glucose transport in fat cells have been discovered. First, in both brown and white fat cells transport per se does not appear to be necessarily rate-limiting for further glucose metabolism. Thus vitamin K5, which markedly increases glucose oxidation by brown fat cells, did not affect the glucose transport system activity. Glucose utilization can apparently be significantly enhanced in fat cells by agents which either increase transport system activity or intracellular enzyme activity. Second, the transport system itself, whether in the basal state or after activation by insulin, lectins, or oxidants, is resistant to sulfhydryl reagents such as N-ethylmaleimide, while the increase in transport activity due to these agents is exquisitely sensitive to sulfhydryl blockage. N-ethylmaleimide blocks the stimulatory effect of insulin on transport whereas addition of insulin to fat cells prior to the reagent completely protects against this inhibitory effect. Further, N-ethylmaleimide prevents the elevated rates of transport system activity due to insulin (or other agents) from returning to basal levels once the cells are washed free of hormone. These data are consistent with the concept that activation of the transport system involves oxidation of key membrane sulfhydryls to the disulfide form, but alternative models are also possible. In any case, these findings provide a possible biochemical clue for future studies designed to identify the specific component(s) involved in the regulatory mechanism which modulates transport of glucose in isolated fat cells."} {"id": "PMID:1272254", "title": "Labelling of oviduct nuclear and nucleolar proteins during estrogen induced differentiation.", "content": "The effect of secondary stimulation with estrogen on synthesis of nuclear and nucleolar proteins is studied in chick oviduct. Isolated nuclei and nucleoli have a protein/DNA ratio of 5.2 and 5.6, respectively. 35% of nuclear and nucleolar protein is recovered in the histone fraction after hydroxylapatite chromatography. Gel electrophoretic separations of nuclear and nucleolar nonhistones are largely similar as to visible bands and distribution of radioactivity. Nucleoli bind 1.4 times more [3H] estradiol as compared to whole nuclei. Nucleolar histones are labelled slightly more actively with [3H] leucine than nuclear histones; nucleolar nonhistones are labelled about 3 times more actively than nuclear nonhistones. An 18 hour secondary stimulation with estrogen increases the radioactivity of histones by 6-fold and that of nonhistones by 2.5-fold in whole nuclei as well as in nucleoli. Stimulation appears to increase preferentially radioactivity of nonhistones at 50 000 daltons. As this change is observed in whole nuclei and nucleoli and is not reduced with hydroxyurea, it is suggested that this may be related to a gross structural reorganisation of chromatin induced by the hormone.", "contents": "Labelling of oviduct nuclear and nucleolar proteins during estrogen induced differentiation. The effect of secondary stimulation with estrogen on synthesis of nuclear and nucleolar proteins is studied in chick oviduct. Isolated nuclei and nucleoli have a protein/DNA ratio of 5.2 and 5.6, respectively. 35% of nuclear and nucleolar protein is recovered in the histone fraction after hydroxylapatite chromatography. Gel electrophoretic separations of nuclear and nucleolar nonhistones are largely similar as to visible bands and distribution of radioactivity. Nucleoli bind 1.4 times more [3H] estradiol as compared to whole nuclei. Nucleolar histones are labelled slightly more actively with [3H] leucine than nuclear histones; nucleolar nonhistones are labelled about 3 times more actively than nuclear nonhistones. An 18 hour secondary stimulation with estrogen increases the radioactivity of histones by 6-fold and that of nonhistones by 2.5-fold in whole nuclei as well as in nucleoli. Stimulation appears to increase preferentially radioactivity of nonhistones at 50 000 daltons. As this change is observed in whole nuclei and nucleoli and is not reduced with hydroxyurea, it is suggested that this may be related to a gross structural reorganisation of chromatin induced by the hormone."} {"id": "PMID:1272255", "title": "Composition of phospholipids and phospholipid fatty acids in rat mast cells.", "content": "The composition of phospholipids and phospholipid fatty acids in isolated rat serous fluid mast cells was analyzed by thin layer chromatography, gas-liquid chromatography and mass spectrometry. The phospholipids constituted about 50% of the mast cell lipids and phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylcholine were identified. The phosphatidylethanolamine fraction contained aldehydes and the highest proportion of unsaturated fatty acids. Sphingomyelin contained predominantly saturated fatty acids whereas the ratio unsaturated fatty acids: saturated fatty acids for the other phospholipids was more close to 1.", "contents": "Composition of phospholipids and phospholipid fatty acids in rat mast cells. The composition of phospholipids and phospholipid fatty acids in isolated rat serous fluid mast cells was analyzed by thin layer chromatography, gas-liquid chromatography and mass spectrometry. The phospholipids constituted about 50% of the mast cell lipids and phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, phosphatidylcholine were identified. The phosphatidylethanolamine fraction contained aldehydes and the highest proportion of unsaturated fatty acids. Sphingomyelin contained predominantly saturated fatty acids whereas the ratio unsaturated fatty acids: saturated fatty acids for the other phospholipids was more close to 1."} {"id": "PMID:1272257", "title": "Polyisoprenoid glycolipids involved in glycoprotein biosynthesis.", "content": "Until five years ago, it was believed that the oligosaccharide chains of most, if not all, glycoproteins were assembled by the stepwise transfer of single sugar residues from their nucleotide derivatives to growing oligosaccharide chains attached to a polypeptide core. It is now becoming widely accepted that polyisoprenol-linked mono- and oligosaccharides function as activated glycosyl carriers in the biosynthesis of some glycoproteins in animal tissues. The lipophilic glycosyl carrier of monosaccharides is the phosphomonoester of dolichol, the C(80-100)-polyisoprenol, containing a saturated terminal isoprene unit. In this biosynthetic process, sugars are initially transferred to dolichol monophosphate from their nucleotide derivatives by membrane-associated glycosyltransferases. These dolichol-linked monosaccharides serve as glycosyl donors in the glycosylation of oligosaccharide phospholipids. It appears likely that dolichol is also the lipid moity of the oligosaccharide intermediates. Detailed enzymatic studies with oligosaccharide phospholipids formed by rat liver, a mouse myeloma tumor and hen oviduct have revealed that these intermediates function as oligosaccharide donors in the assembly of at least one class of glycoproteins. The exact nature of the glycoproteins glycosylated by lipid intermediates and the sub-cellular site(s) of this assembly process remain to be established. The possibility, that the mannose and GlcNAc-containing core found in many glycoproteins, is assembled at the lipid-level is now being investigated. At the current rate of progress in this area of research, the identity of the glycoproteins glycosylated via lipid intermediated and the subcellular site of this assmebly process will soon be known.", "contents": "Polyisoprenoid glycolipids involved in glycoprotein biosynthesis. Until five years ago, it was believed that the oligosaccharide chains of most, if not all, glycoproteins were assembled by the stepwise transfer of single sugar residues from their nucleotide derivatives to growing oligosaccharide chains attached to a polypeptide core. It is now becoming widely accepted that polyisoprenol-linked mono- and oligosaccharides function as activated glycosyl carriers in the biosynthesis of some glycoproteins in animal tissues. The lipophilic glycosyl carrier of monosaccharides is the phosphomonoester of dolichol, the C(80-100)-polyisoprenol, containing a saturated terminal isoprene unit. In this biosynthetic process, sugars are initially transferred to dolichol monophosphate from their nucleotide derivatives by membrane-associated glycosyltransferases. These dolichol-linked monosaccharides serve as glycosyl donors in the glycosylation of oligosaccharide phospholipids. It appears likely that dolichol is also the lipid moity of the oligosaccharide intermediates. Detailed enzymatic studies with oligosaccharide phospholipids formed by rat liver, a mouse myeloma tumor and hen oviduct have revealed that these intermediates function as oligosaccharide donors in the assembly of at least one class of glycoproteins. The exact nature of the glycoproteins glycosylated by lipid intermediates and the sub-cellular site(s) of this assembly process remain to be established. The possibility, that the mannose and GlcNAc-containing core found in many glycoproteins, is assembled at the lipid-level is now being investigated. At the current rate of progress in this area of research, the identity of the glycoproteins glycosylated via lipid intermediated and the subcellular site of this assmebly process will soon be known."} {"id": "PMID:1272258", "title": "Role of tyrosine residues in cytoplasmic aspartate aminotransferase from beef kidney.", "content": "Cytoplasmic aspartate aminotransferase from beef kidney loses 25% of its activity on nitration with tetranitromethane while the apoenzyme about 95%. In the holoenzyme 0.5 tyrosine residue and 1.0 tyrosine residue in the apoenzyme are nitrated per enzyme protomer. In addition 1 cysteine residue per protomer is oxidized in both. The presence of substrates, alpha-ketoglutarate and glutamate, both at ten times their Km values, does not change these results. Mercaptoethanol does not affect the residual activity of either the nitrated holo or apoenzyme. Dithionite abolishes the activity of the nitrated holoenzyme by reducing tha coenzyme moiety. It has no effect on the native holoenzyme or on either the native or nitroapoenzyme.", "contents": "Role of tyrosine residues in cytoplasmic aspartate aminotransferase from beef kidney. Cytoplasmic aspartate aminotransferase from beef kidney loses 25% of its activity on nitration with tetranitromethane while the apoenzyme about 95%. In the holoenzyme 0.5 tyrosine residue and 1.0 tyrosine residue in the apoenzyme are nitrated per enzyme protomer. In addition 1 cysteine residue per protomer is oxidized in both. The presence of substrates, alpha-ketoglutarate and glutamate, both at ten times their Km values, does not change these results. Mercaptoethanol does not affect the residual activity of either the nitrated holo or apoenzyme. Dithionite abolishes the activity of the nitrated holoenzyme by reducing tha coenzyme moiety. It has no effect on the native holoenzyme or on either the native or nitroapoenzyme."} {"id": "PMID:1272259", "title": "Direct demonstration of a complementarity between mRNA and double-stranded sequences of pre-mRNA.", "content": "The total poly(A)-containing mRNA from mouse liver or Ehrlich ascites carcinoma cells was annealed with denatured ds RNA prepared from heavy nuclear 3H-labeled pre-mRNA of the same tissue. The hybrids formed were detected by binding of complexes to poly(U)-Sepharose columns through the poly(A) of mRNA. With this technique, about 30% of labeled ds RNA was bound to poly(U)-Sepharose after annealing it with an mRNA excess. The proportion of hybrid material detected by RNase treatment was two to three times lower than that obtained by poly(U)-Sepharose binding. The length of the RNase-stable acid precipitable hybrid material consisted of heterogeneous sequences of 10-100 nucleotides long when cytoplasmic, and 10-60 nucleotides long when polysomal mRNA was used in the hybridization reaction. The results obtained show that at least some of the mRNA molecules contain sequences complementary to one of the branches of the pre-mRNA hairpins. These results are compatible with the idea that the hairpin-like sequences in pre-mRNA are localized between mRNA and the non-informative part of the precursor molecule.", "contents": "Direct demonstration of a complementarity between mRNA and double-stranded sequences of pre-mRNA. The total poly(A)-containing mRNA from mouse liver or Ehrlich ascites carcinoma cells was annealed with denatured ds RNA prepared from heavy nuclear 3H-labeled pre-mRNA of the same tissue. The hybrids formed were detected by binding of complexes to poly(U)-Sepharose columns through the poly(A) of mRNA. With this technique, about 30% of labeled ds RNA was bound to poly(U)-Sepharose after annealing it with an mRNA excess. The proportion of hybrid material detected by RNase treatment was two to three times lower than that obtained by poly(U)-Sepharose binding. The length of the RNase-stable acid precipitable hybrid material consisted of heterogeneous sequences of 10-100 nucleotides long when cytoplasmic, and 10-60 nucleotides long when polysomal mRNA was used in the hybridization reaction. The results obtained show that at least some of the mRNA molecules contain sequences complementary to one of the branches of the pre-mRNA hairpins. These results are compatible with the idea that the hairpin-like sequences in pre-mRNA are localized between mRNA and the non-informative part of the precursor molecule."} {"id": "PMID:1272260", "title": "The nature of the differential inhibition of polyphenylalanine synthesis in extracts from Artemia salina and rabbit reticulocytes by the Phytolacca americana protein.", "content": "The difference in sensitivity of polyphenylalanine synthesis in extracts from Artemia salina and rabbit reticulocytes to inhibition by the Phytolacca americana protein (PAP) has been found to be linked to the source of the supernatant enzyme fraction and not the ribosomes. In the presence of reticulocyte supernatant enzyme fraction polyphenylalanine synthesis in less sensitive to inhibition by PAP than that observed in the presence of A. salina supernatant enzyme fraction. The results suggest that reticulocyte elongation factor 2 is responsible for this effect.", "contents": "The nature of the differential inhibition of polyphenylalanine synthesis in extracts from Artemia salina and rabbit reticulocytes by the Phytolacca americana protein. The difference in sensitivity of polyphenylalanine synthesis in extracts from Artemia salina and rabbit reticulocytes to inhibition by the Phytolacca americana protein (PAP) has been found to be linked to the source of the supernatant enzyme fraction and not the ribosomes. In the presence of reticulocyte supernatant enzyme fraction polyphenylalanine synthesis in less sensitive to inhibition by PAP than that observed in the presence of A. salina supernatant enzyme fraction. The results suggest that reticulocyte elongation factor 2 is responsible for this effect."} {"id": "PMID:1272261", "title": "The properties of oligonucleotide fragments containing the triphosphorylated 5'-termini of nuclear pre-mRNA from Ehrlich ascites carcinoma cells.", "content": "Triphosphorylated 5'-end fragments 50-150 nucleotides in length were isolated from nuclear pre-mRNA with the aid of a hydroxyapatite chromatography. They are enriched in U and G (28 and 26%, respectively). About 15% of the fragments isolated from poly(U)+RNA contain poly(U) tracks. Neither poly(A)- nor double-stranded sequences were found. Hybridization experiments in conditions of vast DNA excess demonstrated that the 5'-end fragments contain a low amount of highly repetitive sequences but enriched in sequences hybridizing at C0t 1/2 approximately 100.", "contents": "The properties of oligonucleotide fragments containing the triphosphorylated 5'-termini of nuclear pre-mRNA from Ehrlich ascites carcinoma cells. Triphosphorylated 5'-end fragments 50-150 nucleotides in length were isolated from nuclear pre-mRNA with the aid of a hydroxyapatite chromatography. They are enriched in U and G (28 and 26%, respectively). About 15% of the fragments isolated from poly(U)+RNA contain poly(U) tracks. Neither poly(A)- nor double-stranded sequences were found. Hybridization experiments in conditions of vast DNA excess demonstrated that the 5'-end fragments contain a low amount of highly repetitive sequences but enriched in sequences hybridizing at C0t 1/2 approximately 100."} {"id": "PMID:1272262", "title": "Studies on two groups of aminoacyl-tRNA synthetases from rat liver.", "content": "Aminoacyl-tRNA synthetases from rat-liver cytoplasm were fractionated into two groups, characterized by their sedimentation coefficients of about 20S and 5S, respectively. These two groups of synthetases could be isolated from postmicrosomal supernatant either by gradient centrifugation, by gel filtration or by acid treatment at pH 5.2. Both groups were required for maximal amino acid incorporation in a cell-free system.", "contents": "Studies on two groups of aminoacyl-tRNA synthetases from rat liver. Aminoacyl-tRNA synthetases from rat-liver cytoplasm were fractionated into two groups, characterized by their sedimentation coefficients of about 20S and 5S, respectively. These two groups of synthetases could be isolated from postmicrosomal supernatant either by gradient centrifugation, by gel filtration or by acid treatment at pH 5.2. Both groups were required for maximal amino acid incorporation in a cell-free system."} {"id": "PMID:1272263", "title": "Size heterogeneity of the structural units of brain nuclear ribonucleoprotein particles.", "content": "Nuclear ribonucleoprotein particles were examined by electron microscopy after negative staining. The results confirmed the polymeric nature of the particles. The constitutive units were distributed into 4 size classes (diameters varying from 100 to 300 A, approximately) indicating that the monoparticle population was heterogenous. When examined on ultrathin sections, the particles had a fibrillar appearance.", "contents": "Size heterogeneity of the structural units of brain nuclear ribonucleoprotein particles. Nuclear ribonucleoprotein particles were examined by electron microscopy after negative staining. The results confirmed the polymeric nature of the particles. The constitutive units were distributed into 4 size classes (diameters varying from 100 to 300 A, approximately) indicating that the monoparticle population was heterogenous. When examined on ultrathin sections, the particles had a fibrillar appearance."} {"id": "PMID:1272264", "title": "Synthesis of human placental lactogen in Xenopus oocytes.", "content": "Oocytes from Xenopus laevis were injected with polysomes from normal human term placenta. Synthesis of the protein hormone Human Placental Lactogen (HPL) in the oocytes was demonstrated by specific immunoprecipitation with anti-HPL serum. Analysis of the immunoprecipitates on SDS-polyacrylamide gel revealed one peak, with a migration distance corresponding exactly to that of [14C]-Radioacetylated HPL added as a marker. Two days after injection the mRNA was still able to direct the synthesis of HPL.", "contents": "Synthesis of human placental lactogen in Xenopus oocytes. Oocytes from Xenopus laevis were injected with polysomes from normal human term placenta. Synthesis of the protein hormone Human Placental Lactogen (HPL) in the oocytes was demonstrated by specific immunoprecipitation with anti-HPL serum. Analysis of the immunoprecipitates on SDS-polyacrylamide gel revealed one peak, with a migration distance corresponding exactly to that of [14C]-Radioacetylated HPL added as a marker. Two days after injection the mRNA was still able to direct the synthesis of HPL."} {"id": "PMID:1272265", "title": "A code controlling specific binding of regulatory proteins to DNA.", "content": "A possible code is suggested that describes a correspondence between amino acid sequences in stereospecific sites of regulatory proteins and nucleotide sequences at the control sites on DNA. Stereospecific sites of regulatory proteins are assumed to contain pairs of antiparallel polypeptide chain segments which form a right-hand twisted antiparallel beta-sheet with single-stranded regions at the ends of the beta-structure. The binding reaction between regulatory protein and double-helical DNA is accompanied by significant structural alterations at stereospecific sites of the protein and DNA. Half of the hydrogen bonds normally existing in beta-structure are broken upon complex formation with DNA and a new set of hydrogen bonds is formed between polypeptide amide groups and DNA base pairs. The code states a correspondence between four amino acid residues at a stereospecific site of the regulatory protein and an AT (GC) base pair at the control site. It predicts that there are six fundamental amino acid residues (serine, threonine, histidine, asparagine, glutamine and cysteine) whose arrangement in the stereospecific site determines the base pair sequence to which a given regulatory protein would bind preferentially.", "contents": "A code controlling specific binding of regulatory proteins to DNA. A possible code is suggested that describes a correspondence between amino acid sequences in stereospecific sites of regulatory proteins and nucleotide sequences at the control sites on DNA. Stereospecific sites of regulatory proteins are assumed to contain pairs of antiparallel polypeptide chain segments which form a right-hand twisted antiparallel beta-sheet with single-stranded regions at the ends of the beta-structure. The binding reaction between regulatory protein and double-helical DNA is accompanied by significant structural alterations at stereospecific sites of the protein and DNA. Half of the hydrogen bonds normally existing in beta-structure are broken upon complex formation with DNA and a new set of hydrogen bonds is formed between polypeptide amide groups and DNA base pairs. The code states a correspondence between four amino acid residues at a stereospecific site of the regulatory protein and an AT (GC) base pair at the control site. It predicts that there are six fundamental amino acid residues (serine, threonine, histidine, asparagine, glutamine and cysteine) whose arrangement in the stereospecific site determines the base pair sequence to which a given regulatory protein would bind preferentially."} {"id": "PMID:1272266", "title": "A model for the binding of lac repressor to the lac operator.", "content": "A model is suggested for the lac repressor binding to the lac operator in which the repressor polypeptide chain sequences from Gly 14 to Ala 32 and from Ala 53 to Leu 71 are involved in specific interaction with operator DNA. A correspondence between the protein and DNA sequences is found which explains specificity of the repressor binding to the lac operator. The model can be extended to describe specific binding of other regulatory proteins to DNA.", "contents": "A model for the binding of lac repressor to the lac operator. A model is suggested for the lac repressor binding to the lac operator in which the repressor polypeptide chain sequences from Gly 14 to Ala 32 and from Ala 53 to Leu 71 are involved in specific interaction with operator DNA. A correspondence between the protein and DNA sequences is found which explains specificity of the repressor binding to the lac operator. The model can be extended to describe specific binding of other regulatory proteins to DNA."} {"id": "PMID:1272267", "title": "Radiation-induced aneusomic clones in bone marrow of rats.", "content": "Wistar rats 3 months old were given a single whole-body X-irradiation with 700 R. They were killed 9.3 months, on average, after irradiation. From the bone marrows of the 23 irradiated rats, 54 clones of cells with radiation-induced chromosome abnormalities, ranging from 3.3 to 78.3% in size, were obtained. Karyotype analysis at the banding level showed that 43 out of the 54 clones had balanced chromosome constitutions, and that the remaining 11 clones were unbalanced. The 43 balanced clones consisted of 33 clones with reciprocal translocations, 6 with inversions and 4 with both translocations and inversions. The 11 unbalanced clones were made up of 7 aneuploid clones and 4 pseudo-diploid clones. Of the 54 clones, 15 were large with frequencies of more than 25%. Contrary to general belief that cells with unbalanced chromosome constitutions have less capacity to proliferate than those with balanced ones, 8 of the 15 large clones, especially all, except 1, of the largest 6 clones were unbalanced, either aneuploid or pseudo-diploid.", "contents": "Radiation-induced aneusomic clones in bone marrow of rats. Wistar rats 3 months old were given a single whole-body X-irradiation with 700 R. They were killed 9.3 months, on average, after irradiation. From the bone marrows of the 23 irradiated rats, 54 clones of cells with radiation-induced chromosome abnormalities, ranging from 3.3 to 78.3% in size, were obtained. Karyotype analysis at the banding level showed that 43 out of the 54 clones had balanced chromosome constitutions, and that the remaining 11 clones were unbalanced. The 43 balanced clones consisted of 33 clones with reciprocal translocations, 6 with inversions and 4 with both translocations and inversions. The 11 unbalanced clones were made up of 7 aneuploid clones and 4 pseudo-diploid clones. Of the 54 clones, 15 were large with frequencies of more than 25%. Contrary to general belief that cells with unbalanced chromosome constitutions have less capacity to proliferate than those with balanced ones, 8 of the 15 large clones, especially all, except 1, of the largest 6 clones were unbalanced, either aneuploid or pseudo-diploid."} {"id": "PMID:1272268", "title": "Human lymphocytes as target cells in a metabolizing test system in vitro for detecting potential mutagens.", "content": "A metabolizing test system is presented that comprises mouse liver microsomes for metabolic activation of the test compound, NADPH as co-factors, dimethylnitrosamine (DMN) as model mutagen and human peripheral lymphocytes as target cells. Lymphocytes were cultured in RPMI 1640 medium in the presence of phytohemagglutinin for 48 h before being used in the system. Incubation of the lymphocytes for 45 min in the metabolically active system reduced thymidine incorporation by 50%, whereas in the metabolically inactive system without NADPH thymidine incorporation was reduced by 15%. The latter reduction was due to the cytotoxic effects of the mouse liver microsomes and of DMN. When the lymphocytes were cultured for another 24 h after exposure to the metabolizing system and DMN, significant increased formation of chromosomal aberrations such as gaps were observed, cross-overs and breaks being less frequent.", "contents": "Human lymphocytes as target cells in a metabolizing test system in vitro for detecting potential mutagens. A metabolizing test system is presented that comprises mouse liver microsomes for metabolic activation of the test compound, NADPH as co-factors, dimethylnitrosamine (DMN) as model mutagen and human peripheral lymphocytes as target cells. Lymphocytes were cultured in RPMI 1640 medium in the presence of phytohemagglutinin for 48 h before being used in the system. Incubation of the lymphocytes for 45 min in the metabolically active system reduced thymidine incorporation by 50%, whereas in the metabolically inactive system without NADPH thymidine incorporation was reduced by 15%. The latter reduction was due to the cytotoxic effects of the mouse liver microsomes and of DMN. When the lymphocytes were cultured for another 24 h after exposure to the metabolizing system and DMN, significant increased formation of chromosomal aberrations such as gaps were observed, cross-overs and breaks being less frequent."} {"id": "PMID:1272271", "title": "Inhibition of transcription by isonicotinic acid hydrazide.", "content": "Isonicotinic acid hydrazide (INH) reacts with the CMP moiety of a polynucleotide at slightly acid and alkaline pH. The reaction product, when used as a template in the cell-free transcription step, greatly diminishes the incorporation of GMP. In this system we were not able to show that INH -- in contrast with hydrazin -- is potentially capable of producing point mutations, since noncomplementary incorporation could not be observed with a poly(C)/INH adduct as template. Hydrazine could not be detected when INH was incubated with liver-cell fractions.", "contents": "Inhibition of transcription by isonicotinic acid hydrazide. Isonicotinic acid hydrazide (INH) reacts with the CMP moiety of a polynucleotide at slightly acid and alkaline pH. The reaction product, when used as a template in the cell-free transcription step, greatly diminishes the incorporation of GMP. In this system we were not able to show that INH -- in contrast with hydrazin -- is potentially capable of producing point mutations, since noncomplementary incorporation could not be observed with a poly(C)/INH adduct as template. Hydrazine could not be detected when INH was incubated with liver-cell fractions."} {"id": "PMID:1272274", "title": "Reassessment of the use of desferrioxamine B in iron overload.", "content": "Treatment of transfusion-induced iron overload by daily intramuscular injection of the chelator desferrioxamine has not produced impressive urinary iron excretion. We attempted to augment net iron excretion by altering both the route and quantity of chelator administered. Two ascorbic acid-replete patients excreted a mean of 14.5 mg of iron per 24 hours after a single intramuscular injection of 750 mg of desferrioxamine. Excretion increased to a mean of 44.9 mg when this dose was delivered by a continuous 24-hour intravenous infusion. When the intravenous dose of chelator was increased incrementally to as high as 16,000 mg per 24 hours, iron excretion increased up to 180 mg per day. At these high-dose levels, efficiency of binding of iron to chelator was compromised. Constant exposure of the labile iron pool to a chelating agent markedly enhances net iron excretion in splenectomized transfusion-dependent patients.", "contents": "Reassessment of the use of desferrioxamine B in iron overload. Treatment of transfusion-induced iron overload by daily intramuscular injection of the chelator desferrioxamine has not produced impressive urinary iron excretion. We attempted to augment net iron excretion by altering both the route and quantity of chelator administered. Two ascorbic acid-replete patients excreted a mean of 14.5 mg of iron per 24 hours after a single intramuscular injection of 750 mg of desferrioxamine. Excretion increased to a mean of 44.9 mg when this dose was delivered by a continuous 24-hour intravenous infusion. When the intravenous dose of chelator was increased incrementally to as high as 16,000 mg per 24 hours, iron excretion increased up to 180 mg per day. At these high-dose levels, efficiency of binding of iron to chelator was compromised. Constant exposure of the labile iron pool to a chelating agent markedly enhances net iron excretion in splenectomized transfusion-dependent patients."} {"id": "PMID:1272275", "title": "A blood test for multiple sclerosis based on the adherence of lymphocytes to measles-infected cells.", "content": "The increased capacity of lymphocytes from patients with multiple sclerosis to adhere to human epithelial cells persistently infected with measles virus has provided an accurate blood test for multiple sclerosis. When lymphocytes from affected patients were mixed with measles-infected human epithelial cells, the lymphocytes formed rosettes around a mean (+/-S.E.) of 69.2 +/-1.7% of the measles-infected cells. In contrast, lymphocytes from controls, either healthy or with other neurologic and non-neurologic diseases, formed rosettes around a mean of only 28.2+/-2.1% of the measles-infected cells. Of greater importance was the complete absence of overlap between multiple sclerosis and control values, thus indicating the diagnostic potential of the rosetting phenomenon. The severity, duration and activity of the disease had no effect on the degree of rosette formation.", "contents": "A blood test for multiple sclerosis based on the adherence of lymphocytes to measles-infected cells. The increased capacity of lymphocytes from patients with multiple sclerosis to adhere to human epithelial cells persistently infected with measles virus has provided an accurate blood test for multiple sclerosis. When lymphocytes from affected patients were mixed with measles-infected human epithelial cells, the lymphocytes formed rosettes around a mean (+/-S.E.) of 69.2 +/-1.7% of the measles-infected cells. In contrast, lymphocytes from controls, either healthy or with other neurologic and non-neurologic diseases, formed rosettes around a mean of only 28.2+/-2.1% of the measles-infected cells. Of greater importance was the complete absence of overlap between multiple sclerosis and control values, thus indicating the diagnostic potential of the rosetting phenomenon. The severity, duration and activity of the disease had no effect on the degree of rosette formation."} {"id": "PMID:1272283", "title": "Value and limitations of thallium-201 scintigraphy in the acute phase of myocardial infarction.", "content": "We examined the diagnostic usefulness of thallium-201 scintigraphy in 200 patients with acute myocardial infarction. The scintiscans showed a defect, suggesting infarction in 165. In all 44 patients studied iwthin six hours after onset of symptoms the scintiscans indicated a defect. Frequency of positive scans was significantly higher (90 of 96) in patients studied within 24 hours after onset than in those (75 of 104) studied later (p less than 0.01).", "contents": "Value and limitations of thallium-201 scintigraphy in the acute phase of myocardial infarction. We examined the diagnostic usefulness of thallium-201 scintigraphy in 200 patients with acute myocardial infarction. The scintiscans showed a defect, suggesting infarction in 165. In all 44 patients studied iwthin six hours after onset of symptoms the scintiscans indicated a defect. Frequency of positive scans was significantly higher (90 of 96) in patients studied within 24 hours after onset than in those (75 of 104) studied later (p less than 0.01)."} {"id": "PMID:1272284", "title": "The glomerular complement receptor in immunologically mediated renal glomerular injury.", "content": "We examined 25 renal-biopsy specimens to determine whether there is a relation between immunologically mediated renal diseases and the activity of complement receptors that selectively bind antigen-antibody complexes containing activated third component of complement (C3b). These receptors have been termed glomerular complement receptors. Renal lesions associated with in vivo deposition were associated with a loss of receptor sites as demonstrated by reduced or absent in vitro binding of C3b-coated test reagents by glomerular complement receptor. These findings suggest that binding of complement containing immune complexes to glomerular complement receptors in human subjects may participate in the immunopathologic processes of certain immune-complex-mediated renal diseases.", "contents": "The glomerular complement receptor in immunologically mediated renal glomerular injury. We examined 25 renal-biopsy specimens to determine whether there is a relation between immunologically mediated renal diseases and the activity of complement receptors that selectively bind antigen-antibody complexes containing activated third component of complement (C3b). These receptors have been termed glomerular complement receptors. Renal lesions associated with in vivo deposition were associated with a loss of receptor sites as demonstrated by reduced or absent in vitro binding of C3b-coated test reagents by glomerular complement receptor. These findings suggest that binding of complement containing immune complexes to glomerular complement receptors in human subjects may participate in the immunopathologic processes of certain immune-complex-mediated renal diseases."} {"id": "PMID:1272285", "title": "Community medicine: success or failure?", "content": "The development of university-based community-medicine programs represents one of the most fundamental reforms in medical education in recent times. These programs have attempted to train and motivate students to undertake research and innovations in health service and health-care systems, and to provide service to those in need. Since community medicine is based upon the collective needs of population groups, its relevance, value and effectiveness as a teaching, research and service device in the United States must be seriously questioned unless the prevailing system of individualized care is fundamentally changed to one of collective and regionalized organization. Moreover, working with small population groups, university programs do not provide a large enough epidemiologic base to serve as models for this reform. In developing countries community medicine has proved to be ineffective when isolated from broader socioeconomic development, and should, as now constituted, be abandoned as an independent undertaking.", "contents": "Community medicine: success or failure? The development of university-based community-medicine programs represents one of the most fundamental reforms in medical education in recent times. These programs have attempted to train and motivate students to undertake research and innovations in health service and health-care systems, and to provide service to those in need. Since community medicine is based upon the collective needs of population groups, its relevance, value and effectiveness as a teaching, research and service device in the United States must be seriously questioned unless the prevailing system of individualized care is fundamentally changed to one of collective and regionalized organization. Moreover, working with small population groups, university programs do not provide a large enough epidemiologic base to serve as models for this reform. In developing countries community medicine has proved to be ineffective when isolated from broader socioeconomic development, and should, as now constituted, be abandoned as an independent undertaking."} {"id": "PMID:1272299", "title": "Childhood antecedents of adult obesity. Do chubby infants become obese adults?", "content": "We investigated whether obese infants tend to become obese adults. Records of subjects born between 1945 and 1955 were reviewed to select three cohorts based on weight in the first six months of age, which exceeded the 90th percentile at least once, ranged between 25th and 75th percentiles or was below 10th percentile at least once. Three hundred and sixty-six subjects, now between 20 and 30 years of age, were located and their present height and weight determined. Thirty-six per cent of those exceeding the 90th percentile as infants were overweight adults, as compared to 14 per cent of the average age and light-weight infants. A significant increase (chi square = 17.2, p less than 0.001) in adult obesity was evident when the infant exceeded the 75th percentile that was independent of his height. Social class, educational level, and parental weight all correlated with adult weight (p less than 0.001). Sex and ordinal position of birth did not. The data suggest that infant weight correlates strongly with adult weight independently of other factors considered.", "contents": "Childhood antecedents of adult obesity. Do chubby infants become obese adults? We investigated whether obese infants tend to become obese adults. Records of subjects born between 1945 and 1955 were reviewed to select three cohorts based on weight in the first six months of age, which exceeded the 90th percentile at least once, ranged between 25th and 75th percentiles or was below 10th percentile at least once. Three hundred and sixty-six subjects, now between 20 and 30 years of age, were located and their present height and weight determined. Thirty-six per cent of those exceeding the 90th percentile as infants were overweight adults, as compared to 14 per cent of the average age and light-weight infants. A significant increase (chi square = 17.2, p less than 0.001) in adult obesity was evident when the infant exceeded the 75th percentile that was independent of his height. Social class, educational level, and parental weight all correlated with adult weight (p less than 0.001). Sex and ordinal position of birth did not. The data suggest that infant weight correlates strongly with adult weight independently of other factors considered."} {"id": "PMID:1272325", "title": "Parathyroid autotransplantation in primary parathyroid hyperplasia.", "content": "Four patients with primary parathyroid hyperplasia were treated by total parathyroidectomy and autotransplantation of parathyroid tissue into the forearm muscle. All patients remained normocalcemic after vitamin D and oral calcium replacement therapy were stopped at 1 1/2, four, nine and 13 months, respectively. Graft function was documented further by detection of a higher concentration of parathyroid hormone in plasma from the basilic vein draining the graft bed than from the basilic vein in the contralateral arm. Intravenous calcium infusion suppressed parathyroid hormone secretion from the graft whereas hypocalcemia induced by ethylenediaminetetra-acetic acid markedly stimulated hormone release. In two patients histologic examination of a grafted fragment revealed hyperplastic parathyroid tissue. This method of treatment offers a suitable alternative to radical subtotal parathyroidectomy in selected patients with hyperparathyroidism.", "contents": "Parathyroid autotransplantation in primary parathyroid hyperplasia. Four patients with primary parathyroid hyperplasia were treated by total parathyroidectomy and autotransplantation of parathyroid tissue into the forearm muscle. All patients remained normocalcemic after vitamin D and oral calcium replacement therapy were stopped at 1 1/2, four, nine and 13 months, respectively. Graft function was documented further by detection of a higher concentration of parathyroid hormone in plasma from the basilic vein draining the graft bed than from the basilic vein in the contralateral arm. Intravenous calcium infusion suppressed parathyroid hormone secretion from the graft whereas hypocalcemia induced by ethylenediaminetetra-acetic acid markedly stimulated hormone release. In two patients histologic examination of a grafted fragment revealed hyperplastic parathyroid tissue. This method of treatment offers a suitable alternative to radical subtotal parathyroidectomy in selected patients with hyperparathyroidism."} {"id": "PMID:1272327", "title": "The diastolic murmur of renal failure.", "content": "A characteristic and transient early diastolic precordial murmur is commonly heard in patients with renal failure. On the basis of its clinical characteristics, this murmur has previously been attributed to functional aortic incompetence. We undertook a formal cardiac investigation, including aortography, in six of eight patients with renal failure in whom such a bruit developed. Aortic regurgitation was detected in only one of the six. Echocardiography revealed no abnormality of aortic-valve function but did indicate the presence of a small pericardial effusion in each of the five patients examined. We conclude that the early diastolic murmur associated with renal failure does not usually arise from functional aortic incompetence but may be a sound of pericardial origin.", "contents": "The diastolic murmur of renal failure. A characteristic and transient early diastolic precordial murmur is commonly heard in patients with renal failure. On the basis of its clinical characteristics, this murmur has previously been attributed to functional aortic incompetence. We undertook a formal cardiac investigation, including aortography, in six of eight patients with renal failure in whom such a bruit developed. Aortic regurgitation was detected in only one of the six. Echocardiography revealed no abnormality of aortic-valve function but did indicate the presence of a small pericardial effusion in each of the five patients examined. We conclude that the early diastolic murmur associated with renal failure does not usually arise from functional aortic incompetence but may be a sound of pericardial origin."} {"id": "PMID:1272328", "title": "Hemoglobin Beth Israel. A mutant causing clinically apparent cyanosis.", "content": "We found that an abnormal hemoglobin with a very low oxygen affinity was responsible for overt cyanosis in an otherwise healthy adolescent. Hemoglobin Beth Israel, in which serine replaces the asparagine residue normally present at position 102 (G4) of the beta-polypeptide chain, was associated with normal blood counts and no apparent exercise intolerance in the heterozygous carrier. Cyanosis resulted from a drastically right-shifted oxygen dissociation curve, whose position and shape could account for the absence of \"physiologic\" anemia. The whole-blood oxygen tension at 50 per cent oxygen saturation was 88 mm Hg (normally 26 +/- 1 mm Hg), and the arterial blood was only 63 per cent saturated with oxygen despite a normal oxygen tension of 97 mm Hg. The hemolysate showed a low oxygen affinity but normal Bohr effect. Unexplained cyanosis, particularly in association with normal arterial oxygen tension should prompt a search for an abnormal hemoglobin, which may obviate the need for invasive diagnostic procedures.", "contents": "Hemoglobin Beth Israel. A mutant causing clinically apparent cyanosis. We found that an abnormal hemoglobin with a very low oxygen affinity was responsible for overt cyanosis in an otherwise healthy adolescent. Hemoglobin Beth Israel, in which serine replaces the asparagine residue normally present at position 102 (G4) of the beta-polypeptide chain, was associated with normal blood counts and no apparent exercise intolerance in the heterozygous carrier. Cyanosis resulted from a drastically right-shifted oxygen dissociation curve, whose position and shape could account for the absence of \"physiologic\" anemia. The whole-blood oxygen tension at 50 per cent oxygen saturation was 88 mm Hg (normally 26 +/- 1 mm Hg), and the arterial blood was only 63 per cent saturated with oxygen despite a normal oxygen tension of 97 mm Hg. The hemolysate showed a low oxygen affinity but normal Bohr effect. Unexplained cyanosis, particularly in association with normal arterial oxygen tension should prompt a search for an abnormal hemoglobin, which may obviate the need for invasive diagnostic procedures."} {"id": "PMID:1272329", "title": "Gluten-sensitive enteropathy. Inhibition by cortisol of the effect of gluten protein in vitro.", "content": "Cortisol partially prevents the harmful effect of gluten on the jejunal mucosa of patients with gluten-sensitive enteropathy. To investigate further the pathogenesis of this disorder, we analyzed the effect of cortisol in cultures of jejunal specimens obtained by biopsy. Cultures were done with and without gluten or cortisol. Morphology and alkaline phosphatase activity were assessed before and after 24 hours. Biopsies from untreated patients cultured with gluten showed low enzyme values and cuboidal epithelial cells before and after culture. Biopsies cultured in a gluten-free medium showed a threefold increase in enzyme values (P less than 0.01) and morphologic improvement with change to columnar epithelial cells. Cultures with gluten plus cortisol showed rises in alkaline phosphatase and morphologic improvement indistinguishable from cultures without gluten. Cortisol and gluten had no effect on cultures from appropriate controls. Cortisol thus prevents the harmful effects of gluten on biopsies from patients with gluten-sensitive enteropathy in vitro.", "contents": "Gluten-sensitive enteropathy. Inhibition by cortisol of the effect of gluten protein in vitro. Cortisol partially prevents the harmful effect of gluten on the jejunal mucosa of patients with gluten-sensitive enteropathy. To investigate further the pathogenesis of this disorder, we analyzed the effect of cortisol in cultures of jejunal specimens obtained by biopsy. Cultures were done with and without gluten or cortisol. Morphology and alkaline phosphatase activity were assessed before and after 24 hours. Biopsies from untreated patients cultured with gluten showed low enzyme values and cuboidal epithelial cells before and after culture. Biopsies cultured in a gluten-free medium showed a threefold increase in enzyme values (P less than 0.01) and morphologic improvement with change to columnar epithelial cells. Cultures with gluten plus cortisol showed rises in alkaline phosphatase and morphologic improvement indistinguishable from cultures without gluten. Cortisol and gluten had no effect on cultures from appropriate controls. Cortisol thus prevents the harmful effects of gluten on biopsies from patients with gluten-sensitive enteropathy in vitro."} {"id": "PMID:1272330", "title": "Echocardiography in bacterial endocarditis.", "content": "We examined 129 standard M-mode echocardiograms obtained in 65 patients (16 to 73 years old) with bacterial endocarditis. Twenty of the 22 patients with vegetations recognizable by echocargiography died, or underwent cardiac operation (mean interval from admission 22 days, and range two to 120 days). Vegetations were seen on the echocardiograms in 22 (aortic 10, mitral nine and tricuspid three, with anatomic confirmation in 19). Of patients without vegetations on echocardiography none underwent emergency operation or died as a result of cardiac disease (mean follow-up period of 14 months, range of two to 38 months). Other echocardiographic findings in those with vegetations included early mitral-valve closure (six), \"flail\" aortic leaflet (three), and \"flail\" mitral leaflet (three). Echocardiography can provide a rapid, reliable noninvasive diagnosis of bacterial vegetations in certain patients with bacterial endocarditis and may identify patients with more severe disease who may require operative intervention.", "contents": "Echocardiography in bacterial endocarditis. We examined 129 standard M-mode echocardiograms obtained in 65 patients (16 to 73 years old) with bacterial endocarditis. Twenty of the 22 patients with vegetations recognizable by echocargiography died, or underwent cardiac operation (mean interval from admission 22 days, and range two to 120 days). Vegetations were seen on the echocardiograms in 22 (aortic 10, mitral nine and tricuspid three, with anatomic confirmation in 19). Of patients without vegetations on echocardiography none underwent emergency operation or died as a result of cardiac disease (mean follow-up period of 14 months, range of two to 38 months). Other echocardiographic findings in those with vegetations included early mitral-valve closure (six), \"flail\" aortic leaflet (three), and \"flail\" mitral leaflet (three). Echocardiography can provide a rapid, reliable noninvasive diagnosis of bacterial vegetations in certain patients with bacterial endocarditis and may identify patients with more severe disease who may require operative intervention."} {"id": "PMID:1272331", "title": "Neighborhood health centers as providers of primary mental-health care.", "content": "The 19 Boston neighborhood health centers with mental-health programs were studied to investigate the delivery of mental-health services as part of a primary health-care system. Staff-time utilization data show these programs focus on the provision of primary mental-health services to neighborhood residents and indirect consultative and collaborative services to general health staff to co-ordinate health care. Forty-eight per cent of referrals for mental-health services were patients first identified and referred by general health staff. Children constituted a disproportionately high percentage of the patients served (43 per cent), and 22 per cent of the services were outreach visits, primarily in patients' homes. Quantitative studies are necessary to confirm my qualititative findings that the conjoint health and mental-health delivery site at the neighborhood level increases the accessibility and psychologic acceptability of mental-health services and enhances case finding, successful referral, and co-ordination of primary health care.", "contents": "Neighborhood health centers as providers of primary mental-health care. The 19 Boston neighborhood health centers with mental-health programs were studied to investigate the delivery of mental-health services as part of a primary health-care system. Staff-time utilization data show these programs focus on the provision of primary mental-health services to neighborhood residents and indirect consultative and collaborative services to general health staff to co-ordinate health care. Forty-eight per cent of referrals for mental-health services were patients first identified and referred by general health staff. Children constituted a disproportionately high percentage of the patients served (43 per cent), and 22 per cent of the services were outreach visits, primarily in patients' homes. Quantitative studies are necessary to confirm my qualititative findings that the conjoint health and mental-health delivery site at the neighborhood level increases the accessibility and psychologic acceptability of mental-health services and enhances case finding, successful referral, and co-ordination of primary health care."} {"id": "PMID:1272347", "title": "Acute renal failure of glomerular origin during visceral abscesses.", "content": "We studied 11 patients who had visceral abscesses and in whom acute renal failure developed. All renal biopsies showed a diffuse proliferative and crescentig glomerulonephritis. In seven patients blood cultures were repeatedly negative. Endocarditis could be ruled out in six patients. Seven patients had circulating cryoglobulins; serum complement levels were normal in seven and decreased in four; circulating immune complexes were found in the three patients studied. The evolution of the glomerulonephritis, documented by serial biopsies, closely paralleled the course of the infection. A complete recovery of renal function occurred in four cases in which a rapid and complete cure of the infection was obtained. Of five patients in whom the infection was not cured, four died, and chronic renal failure developed in one. In two patients in whom therapy was delayed, chronic renal failure also developed. Deep suppuration, even in the absence of bacteremia, may be responsible for a severe but possibly reversible glomerulonephritis with circulating immune complexes.", "contents": "Acute renal failure of glomerular origin during visceral abscesses. We studied 11 patients who had visceral abscesses and in whom acute renal failure developed. All renal biopsies showed a diffuse proliferative and crescentig glomerulonephritis. In seven patients blood cultures were repeatedly negative. Endocarditis could be ruled out in six patients. Seven patients had circulating cryoglobulins; serum complement levels were normal in seven and decreased in four; circulating immune complexes were found in the three patients studied. The evolution of the glomerulonephritis, documented by serial biopsies, closely paralleled the course of the infection. A complete recovery of renal function occurred in four cases in which a rapid and complete cure of the infection was obtained. Of five patients in whom the infection was not cured, four died, and chronic renal failure developed in one. In two patients in whom therapy was delayed, chronic renal failure also developed. Deep suppuration, even in the absence of bacteremia, may be responsible for a severe but possibly reversible glomerulonephritis with circulating immune complexes."} {"id": "PMID:1272348", "title": "Systemic embolism in chronic sinoatrial disorder.", "content": "We attempted to estimate the prevalence of systemic embolism in patients with chronic sino-atrial disorder. In a group of 100 patients, evidence of embolism was found in 16, of whom 15 had the bradycardia-tachycardia syndrome. In 712 controls with chronic complete heart block, who were matched for age and sex, embolism had occurred in only 1.3 per cent (P less than 0.001). A second group of 41 patients with chronic ventricular bradycardia and atrial flutter or fibrillation had an embolic prevalence of 7.3 per cent, which was also greater than that in the controls (P less than 0.05). All patients with sinoatrial disorder in whom systemic embolism developed were over 54 years of age; multiple episodes occurred in six. The risk of embolization remains even if the bradycardia-tachycardia syndrome is replaced by stable atrial fibrillation. Impaired atrial function appears to be a key factor in predisposing to intracardiac thrombosis, and paroxysmal supraventricular tachycardia increases the risk of subsequent embolization.", "contents": "Systemic embolism in chronic sinoatrial disorder. We attempted to estimate the prevalence of systemic embolism in patients with chronic sino-atrial disorder. In a group of 100 patients, evidence of embolism was found in 16, of whom 15 had the bradycardia-tachycardia syndrome. In 712 controls with chronic complete heart block, who were matched for age and sex, embolism had occurred in only 1.3 per cent (P less than 0.001). A second group of 41 patients with chronic ventricular bradycardia and atrial flutter or fibrillation had an embolic prevalence of 7.3 per cent, which was also greater than that in the controls (P less than 0.05). All patients with sinoatrial disorder in whom systemic embolism developed were over 54 years of age; multiple episodes occurred in six. The risk of embolization remains even if the bradycardia-tachycardia syndrome is replaced by stable atrial fibrillation. Impaired atrial function appears to be a key factor in predisposing to intracardiac thrombosis, and paroxysmal supraventricular tachycardia increases the risk of subsequent embolization."} {"id": "PMID:1272349", "title": "Chilean medicine under social revolution.", "content": "During the last decade Chile has experienced a series of social changes under Christian Socialist (1964-1970), Marxist Socialist (1970-1973) and military (1973-1975) governments. These changes grossly affected the evolution of medicine and public health in Chile. Nevertheless, vital statistics show an overall improvement in health indexes, with a short interruption during the Marxist government. During this period medical standards and the quality of medical services declined when revolutionaries disrupted the organization of traditional socialized Chilean medicine founded 50 years ago. The vital statistics of 1974 suggest an overall recovery, but physical and human resources for health, eroded by revolution and the present acute economic crisis, have not yet begun to improve. Nevertheless, Chilean medicine has reasumed the technical character that should never have been abandoned.", "contents": "Chilean medicine under social revolution. During the last decade Chile has experienced a series of social changes under Christian Socialist (1964-1970), Marxist Socialist (1970-1973) and military (1973-1975) governments. These changes grossly affected the evolution of medicine and public health in Chile. Nevertheless, vital statistics show an overall improvement in health indexes, with a short interruption during the Marxist government. During this period medical standards and the quality of medical services declined when revolutionaries disrupted the organization of traditional socialized Chilean medicine founded 50 years ago. The vital statistics of 1974 suggest an overall recovery, but physical and human resources for health, eroded by revolution and the present acute economic crisis, have not yet begun to improve. Nevertheless, Chilean medicine has reasumed the technical character that should never have been abandoned."} {"id": "PMID:1272392", "title": "Isolation and N-terminal amino acid sequence of membrane-bound human HLA-A and HLA-B antigens.", "content": "Membrane-bound HLA-A and HLA-B antigens have been extensively purified in good yield. The sequences of the N-terminal 16 amino acids have been determined using about 1 nmol of protein eluted from polyacrylamide gel after electrophoresis in sodium dodecyl sulphate.", "contents": "Isolation and N-terminal amino acid sequence of membrane-bound human HLA-A and HLA-B antigens. Membrane-bound HLA-A and HLA-B antigens have been extensively purified in good yield. The sequences of the N-terminal 16 amino acids have been determined using about 1 nmol of protein eluted from polyacrylamide gel after electrophoresis in sodium dodecyl sulphate."} {"id": "PMID:1272456", "title": "[Reactions of neurons in the primary and secondary somatosensory zones of the cortex to stimulation of the ventral posterior nucleus of the thalamus].", "content": "Neuronal responses in the first and second somatosensory cortex (SI and SII) to stimulation of the ventroposterior nucleus of the thalamus (VP) were studied in experiments on cats immobilized with d-tubocurarine. 12.0% responding neurons in SI and 9.5% in SII were activated antidromically by VP stimulation. In the majority of antidromic responses the latencies did not exceed 1.0 ms. The minimal latency of orthodromic spikes was 1.5 ms in SI and 1.7 ms in SII. In SI the number of neurons whose orthodromic spike latencies did not exceed 3.0 ms was larger than neurons activated with latencies of 3.1-4.5 ms. In SII an inverse quantitative relationship between those two neuronal groups was observed. In SII a significantly larger number of neurons was excited with latencies of EPSPs ranged between 1.1-9.0 ms in SI and between 1.4-6.6 ms in SII and the latencies of IPSPs between 1.5-6.8 ms in SI and 2.2-9.4 ms in SII. The importance of different pathways for excitatory and inhibitory VP influences to neurons of SI and SII is discussed.", "contents": "[Reactions of neurons in the primary and secondary somatosensory zones of the cortex to stimulation of the ventral posterior nucleus of the thalamus]. Neuronal responses in the first and second somatosensory cortex (SI and SII) to stimulation of the ventroposterior nucleus of the thalamus (VP) were studied in experiments on cats immobilized with d-tubocurarine. 12.0% responding neurons in SI and 9.5% in SII were activated antidromically by VP stimulation. In the majority of antidromic responses the latencies did not exceed 1.0 ms. The minimal latency of orthodromic spikes was 1.5 ms in SI and 1.7 ms in SII. In SI the number of neurons whose orthodromic spike latencies did not exceed 3.0 ms was larger than neurons activated with latencies of 3.1-4.5 ms. In SII an inverse quantitative relationship between those two neuronal groups was observed. In SII a significantly larger number of neurons was excited with latencies of EPSPs ranged between 1.1-9.0 ms in SI and between 1.4-6.6 ms in SII and the latencies of IPSPs between 1.5-6.8 ms in SI and 2.2-9.4 ms in SII. The importance of different pathways for excitatory and inhibitory VP influences to neurons of SI and SII is discussed."} {"id": "PMID:1272457", "title": "[Spatial organization of the direct connections of the sensory-motor cortex with the rhombencephalon and spinal cord in cats].", "content": "The distribution and ultrastructure of terminals of corticofugal fibres in the cat hindbrain and spinal cord were examined by light and electron microscopy in various periods of experimental degeneration elicited by large or small sensorimotor cortex destructions. Using the Fink-Heimer technique, it is shown that the corticofugal projections in the dorsal column nuclei and in the spinal intermediate zone are somatotopically arranged. Even small restricted areas of sensorimotor cortex give two separate descending supraspinal systems. The fibres of the first system are distributed in the dorsolateral and dorsolmedial parts of the spinal intermediate zone, predominantly contralaterally. The fibres of the second system are distributed in the dorsolateral and ventromedial parts of the intermediate zone (bilaterally). Degenerating axo-somatic and axo-dendritic contacts contain spherical vesicles. The majority of degenerating axons in n. cuneatus are 0.5-1,5 mu in diameter. The data obtained are discussed in connection with the electrophysiological data on the mechanisms of the cortical control of the spinal cord neuronal activity.", "contents": "[Spatial organization of the direct connections of the sensory-motor cortex with the rhombencephalon and spinal cord in cats]. The distribution and ultrastructure of terminals of corticofugal fibres in the cat hindbrain and spinal cord were examined by light and electron microscopy in various periods of experimental degeneration elicited by large or small sensorimotor cortex destructions. Using the Fink-Heimer technique, it is shown that the corticofugal projections in the dorsal column nuclei and in the spinal intermediate zone are somatotopically arranged. Even small restricted areas of sensorimotor cortex give two separate descending supraspinal systems. The fibres of the first system are distributed in the dorsolateral and dorsolmedial parts of the spinal intermediate zone, predominantly contralaterally. The fibres of the second system are distributed in the dorsolateral and ventromedial parts of the intermediate zone (bilaterally). Degenerating axo-somatic and axo-dendritic contacts contain spherical vesicles. The majority of degenerating axons in n. cuneatus are 0.5-1,5 mu in diameter. The data obtained are discussed in connection with the electrophysiological data on the mechanisms of the cortical control of the spinal cord neuronal activity."} {"id": "PMID:1272458", "title": "[Changes in the synaptic contacts in the amygdaloid complex following unilateral lobectomy in rabbits].", "content": "Synaptic junctions in the rabbit amygdala were studied by electron microscopy. A definite distribution of morphologically different synapses on the neuronal surface was noticed. This distribution changed 3 days after ipsilateral lobectomy. A suggestion is made on transformation of a certain morphological form of synaptic contact into another one during the changed function.", "contents": "[Changes in the synaptic contacts in the amygdaloid complex following unilateral lobectomy in rabbits]. Synaptic junctions in the rabbit amygdala were studied by electron microscopy. A definite distribution of morphologically different synapses on the neuronal surface was noticed. This distribution changed 3 days after ipsilateral lobectomy. A suggestion is made on transformation of a certain morphological form of synaptic contact into another one during the changed function."} {"id": "PMID:1272459", "title": "[The predominantly unilateral influence of the posterior hypothalamus on the neocortex].", "content": "High-frequency electrical stimulation of the-posterior hypothalamus applied 10-20 days after the sectioning of the brain stem at the level of the anterior frontal margins of the anterior coliculus results in the preferential activation of the ipsilateral neocortex. When unilateral lesions are placed in the posterior hypothalamus, the predominance of synchronous activity in the ipsilateral neocortex is observed. In the premesencephalic preparations, weak single electrical stimulation of the posterior hypothalamus provokes spindles in the ipsilateral portions of the frontal cortex. At more intensive single stimulation of the posterior hypothalamus there occurs diffuse appearance of spindles in different neocortical areas. Besides the preferential unilateral effect, the influence of the posterior hypothalamus is more prominent in the frontal than in the occipital regions of the cortex. It is suggested that the posterior hypothalamus exerts its influence on the neocortex through the thalamic nuclei.", "contents": "[The predominantly unilateral influence of the posterior hypothalamus on the neocortex]. High-frequency electrical stimulation of the-posterior hypothalamus applied 10-20 days after the sectioning of the brain stem at the level of the anterior frontal margins of the anterior coliculus results in the preferential activation of the ipsilateral neocortex. When unilateral lesions are placed in the posterior hypothalamus, the predominance of synchronous activity in the ipsilateral neocortex is observed. In the premesencephalic preparations, weak single electrical stimulation of the posterior hypothalamus provokes spindles in the ipsilateral portions of the frontal cortex. At more intensive single stimulation of the posterior hypothalamus there occurs diffuse appearance of spindles in different neocortical areas. Besides the preferential unilateral effect, the influence of the posterior hypothalamus is more prominent in the frontal than in the occipital regions of the cortex. It is suggested that the posterior hypothalamus exerts its influence on the neocortex through the thalamic nuclei."} {"id": "PMID:1272460", "title": "[The influence of aconitine on several properties of the sodium channels of the membranes of nodes of Ranvier].", "content": "Effect of aconitine on the sodium channels in the frog Ranvier node membrane was studied. Aconitine was shown to produce two types of modified channels. The first type channels acquire stable properties after effect was developed; they open at high negative voltage, their inactivation, if any, is incomplete, their selectivity is greatly reduced: the potassium-sodium permeability ratio averages to 0.72. The second type channels turn impermeable as effect develops, their kinetics and conductance-voltage dependance are similar to those of normal sodium channels; as compared with normal channels their selectivity is reduced: the potassium permeability ratio averages to 0.22. Both aconitine-modified and normal channels have the same sensitivity to tetrodotoxin.", "contents": "[The influence of aconitine on several properties of the sodium channels of the membranes of nodes of Ranvier]. Effect of aconitine on the sodium channels in the frog Ranvier node membrane was studied. Aconitine was shown to produce two types of modified channels. The first type channels acquire stable properties after effect was developed; they open at high negative voltage, their inactivation, if any, is incomplete, their selectivity is greatly reduced: the potassium-sodium permeability ratio averages to 0.72. The second type channels turn impermeable as effect develops, their kinetics and conductance-voltage dependance are similar to those of normal sodium channels; as compared with normal channels their selectivity is reduced: the potassium permeability ratio averages to 0.22. Both aconitine-modified and normal channels have the same sensitivity to tetrodotoxin."} {"id": "PMID:1272461", "title": "[Several characteristics of afferent flow following skin injuries].", "content": "Using a crosscorrelation method, the quantitative characteristics of afferent impulse flow in the n. saphenus were investigated under stimulation of cat's skin with acid, needles, and pins. The appearance of the nociceptive reaction served as a noxious stimulation test. Noxious mechanical and chemical stimuli affecting directly the nerve fibres activate the same afferent fibres as those activated by weak tactile ones exciting the receptors. The impulse flows under such conditions differ by the amount of active A and C fibres, their correlation and the activity duration in them. The nociceptive reaction is realized owing to a considerable predominance of activity in C fibres over that in A fibres and owing to the long activity duration in both kinds of fibres, particularly in C fibres. The paper demonstrates the possibility to use an optic correlometer for the analysis of the activity in a whole nerve.", "contents": "[Several characteristics of afferent flow following skin injuries]. Using a crosscorrelation method, the quantitative characteristics of afferent impulse flow in the n. saphenus were investigated under stimulation of cat's skin with acid, needles, and pins. The appearance of the nociceptive reaction served as a noxious stimulation test. Noxious mechanical and chemical stimuli affecting directly the nerve fibres activate the same afferent fibres as those activated by weak tactile ones exciting the receptors. The impulse flows under such conditions differ by the amount of active A and C fibres, their correlation and the activity duration in them. The nociceptive reaction is realized owing to a considerable predominance of activity in C fibres over that in A fibres and owing to the long activity duration in both kinds of fibres, particularly in C fibres. The paper demonstrates the possibility to use an optic correlometer for the analysis of the activity in a whole nerve."} {"id": "PMID:1272462", "title": "[Separation of the sodium and potassium channels in the surface membrane of mollusk nerve cells].", "content": "Characteristics of transmembrane ionic currents under controlled changes in ionic composition of extra-and intracellular medium were studied by means of intracellular dialysis and voltage clamp in isolated neurons from the molluscs Helix pomatia and Limnea stagnalis. The outward potassium currents were eliminated by replacement of intracellular potassium by Tris and the pure inward current could be measured. Replacement of the Ringer solution by NA-free or Ca-free solutions in the extracellular medium made it possible to separate the inward current into additive components, one of which is carried by sodium ions, and the other, by calcium ions. The sodium and calcium inward currents are shown to have different kinetics and potential dependence: taumNa = 1+/-0.5 ms, taumCa = = 3+/-1 ms, tauhNa = 8+/-2 ms, tauhCa = 115+/-10 ms when Vm = 0, GNa = 0.5 when Vm==-21+/-2 mV, GCa = 0.5 when Vm=-8+/-2 mV. Both currents were not altered by tetrodoxin (TTX), however calcium current is specifically blocked by externally applied calcium ions (2 X 10(-3) M), verapamil, D = 600 as well as by fluoride while introduced inside a cell. These data prove the existence of separate systems of sodium and calcium ion-conducting channels in the somatic membrane.", "contents": "[Separation of the sodium and potassium channels in the surface membrane of mollusk nerve cells]. Characteristics of transmembrane ionic currents under controlled changes in ionic composition of extra-and intracellular medium were studied by means of intracellular dialysis and voltage clamp in isolated neurons from the molluscs Helix pomatia and Limnea stagnalis. The outward potassium currents were eliminated by replacement of intracellular potassium by Tris and the pure inward current could be measured. Replacement of the Ringer solution by NA-free or Ca-free solutions in the extracellular medium made it possible to separate the inward current into additive components, one of which is carried by sodium ions, and the other, by calcium ions. The sodium and calcium inward currents are shown to have different kinetics and potential dependence: taumNa = 1+/-0.5 ms, taumCa = = 3+/-1 ms, tauhNa = 8+/-2 ms, tauhCa = 115+/-10 ms when Vm = 0, GNa = 0.5 when Vm==-21+/-2 mV, GCa = 0.5 when Vm=-8+/-2 mV. Both currents were not altered by tetrodoxin (TTX), however calcium current is specifically blocked by externally applied calcium ions (2 X 10(-3) M), verapamil, D = 600 as well as by fluoride while introduced inside a cell. These data prove the existence of separate systems of sodium and calcium ion-conducting channels in the somatic membrane."} {"id": "PMID:1272463", "title": "[Changes in the phasic evoked activity of cortical neurons following iontophoretic application of glutamate, GABA and atropine].", "content": "L-glutamic acid, GABA and atropine were applied ionophoretically from a microelectrode to single neurons in the somatosensory cortex of awake rabbits. The influence of the substances varied for the separate neuron response phases and depended on changes in electric stimulation parameters. A conclusion is made on the chemical specificity of separate phases of the neuronal responses and the neurochemical nature of the changes in the receptive fields of central neurons.", "contents": "[Changes in the phasic evoked activity of cortical neurons following iontophoretic application of glutamate, GABA and atropine]. L-glutamic acid, GABA and atropine were applied ionophoretically from a microelectrode to single neurons in the somatosensory cortex of awake rabbits. The influence of the substances varied for the separate neuron response phases and depended on changes in electric stimulation parameters. A conclusion is made on the chemical specificity of separate phases of the neuronal responses and the neurochemical nature of the changes in the receptive fields of central neurons."} {"id": "PMID:1272466", "title": "[Corticofugal influences on the background activity of the rabbit lateral geniculate body].", "content": "Two groups of P-neurons were found in the rabbit lateral geniculate body: with lowfrequency and high-frequency background activity. The background activity of the low-frequency neurons was subjected mainly to facilitatory coritcofugal influences. Inhibitory corticofugal influences predominated in the regulation of background activity of high-frequency neurons.", "contents": "[Corticofugal influences on the background activity of the rabbit lateral geniculate body]. Two groups of P-neurons were found in the rabbit lateral geniculate body: with lowfrequency and high-frequency background activity. The background activity of the low-frequency neurons was subjected mainly to facilitatory coritcofugal influences. Inhibitory corticofugal influences predominated in the regulation of background activity of high-frequency neurons."} {"id": "PMID:1272467", "title": "[Comparative characteristics of interneuronal dimensions in the cervical segments of the cat spinal cord].", "content": "A comparative study of interneuronal dimensions in segments C1, C4, C7 was performed for the cat cervical spinal cord. It is shown that in three groups of interneurons the mean values of the two somatic axes, the correlation coefficients of these values and the mean volumes of the cell somata are the greatest in the C7 segment and the smallest in the C6 segment.", "contents": "[Comparative characteristics of interneuronal dimensions in the cervical segments of the cat spinal cord]. A comparative study of interneuronal dimensions in segments C1, C4, C7 was performed for the cat cervical spinal cord. It is shown that in three groups of interneurons the mean values of the two somatic axes, the correlation coefficients of these values and the mean volumes of the cell somata are the greatest in the C7 segment and the smallest in the C6 segment."} {"id": "PMID:1272469", "title": "Ultrastructure of human uveal melanomas cultivated in vitro.", "content": "Ultrastructural characteristics of four mixed-cell type human uveal melanomas cultivated in vitro were described. The authors stress the significance of melanosome microtubules in the process of melaninisation. They also stress the significance of smooth membraness for the formation of premelanosomes. The question of differentiation between melanocytes and lysosomes in ultrastructure is discussed.", "contents": "Ultrastructure of human uveal melanomas cultivated in vitro. Ultrastructural characteristics of four mixed-cell type human uveal melanomas cultivated in vitro were described. The authors stress the significance of melanosome microtubules in the process of melaninisation. They also stress the significance of smooth membraness for the formation of premelanosomes. The question of differentiation between melanocytes and lysosomes in ultrastructure is discussed."} {"id": "PMID:1272470", "title": "Cytology of delayed hypersensitivity reaction in patients with malignant tumors.", "content": "A modification of the \"skin window\" method is proposed for investigation of delayed hypersensitivity in patients with tumors. The principle of the modified method consists in an antigen injection into the site of lesion. Patients with tumors showed a strikingly lowered lymphoid cells and eosinophilic and basophilic granulocytes than the controls.", "contents": "Cytology of delayed hypersensitivity reaction in patients with malignant tumors. A modification of the \"skin window\" method is proposed for investigation of delayed hypersensitivity in patients with tumors. The principle of the modified method consists in an antigen injection into the site of lesion. Patients with tumors showed a strikingly lowered lymphoid cells and eosinophilic and basophilic granulocytes than the controls."} {"id": "PMID:1272471", "title": "Are the tumor cells of the G2 period of the cell cycle sensitive to the immune pressure?", "content": "The present work was aimed at analysing as to whether the cell loss is random within the cell cycle or not. In order to verify the former statement two regressing tumor systems: Ehrlich ascites carcinoma transplated into rats (heterologous graft) and BN/b lymphoma implanted into immunized BN/b mice (syngeneic graft), were used. Both tumor lines were examined by means of double labeling method coupled with short colcemide block. In the case of regressing tumors the cell flux into DNA synthesis was found to be at the same level as for the growing tumors. On the contrary, the flux into mitosis was much lower for regressing tumors than for growing ones. The above results suggest the immune attack on tumor cells while in the G2 phase of the cell cycle.", "contents": "Are the tumor cells of the G2 period of the cell cycle sensitive to the immune pressure? The present work was aimed at analysing as to whether the cell loss is random within the cell cycle or not. In order to verify the former statement two regressing tumor systems: Ehrlich ascites carcinoma transplated into rats (heterologous graft) and BN/b lymphoma implanted into immunized BN/b mice (syngeneic graft), were used. Both tumor lines were examined by means of double labeling method coupled with short colcemide block. In the case of regressing tumors the cell flux into DNA synthesis was found to be at the same level as for the growing tumors. On the contrary, the flux into mitosis was much lower for regressing tumors than for growing ones. The above results suggest the immune attack on tumor cells while in the G2 phase of the cell cycle."} {"id": "PMID:1272472", "title": "The effect of dibromodulcitol (Elobromolr, Mitolactolr, nsc 104 800) on the postoperative recurrences of the Guerin carcinoma of the rat.", "content": "In all cases of Guerin carcinoma of the rat the recurrence of the tumor in 7-10 days can be observed following surgical removal. Local treatment with Dibromodulcitol combined with intraperitoneal administration of the same drug results in delayed occurrence of tumor recurrences, the growth of which is slower, and in a significant increase of life span of the animals. In exceptional cases no recurrence appeared. The local treatment combined with intraperitoneal administration was the most effective. Peroral treatment was also effective although in a lesser degree.", "contents": "The effect of dibromodulcitol (Elobromolr, Mitolactolr, nsc 104 800) on the postoperative recurrences of the Guerin carcinoma of the rat. In all cases of Guerin carcinoma of the rat the recurrence of the tumor in 7-10 days can be observed following surgical removal. Local treatment with Dibromodulcitol combined with intraperitoneal administration of the same drug results in delayed occurrence of tumor recurrences, the growth of which is slower, and in a significant increase of life span of the animals. In exceptional cases no recurrence appeared. The local treatment combined with intraperitoneal administration was the most effective. Peroral treatment was also effective although in a lesser degree."} {"id": "PMID:1272473", "title": "Incorporation of 3H-dibromodulcitol and 3H-dianhydrodulcitol into ascites tumor cells. Autoradiographic study.", "content": "The incorporation of 3H-Dibromodulcitol and 3H-Dianhydrodulcitol into S37 ascites tumor cells has been studied with autoradiography. Both drugs war incorporated very rapidly into the cells. The labeling of nucleus was higher than that of cytoplasm. A slight accumulation of grains was found above the condensed chromatin and along the membranes. The uptake of DAD has been more intensive than that of DBD.", "contents": "Incorporation of 3H-dibromodulcitol and 3H-dianhydrodulcitol into ascites tumor cells. Autoradiographic study. The incorporation of 3H-Dibromodulcitol and 3H-Dianhydrodulcitol into S37 ascites tumor cells has been studied with autoradiography. Both drugs war incorporated very rapidly into the cells. The labeling of nucleus was higher than that of cytoplasm. A slight accumulation of grains was found above the condensed chromatin and along the membranes. The uptake of DAD has been more intensive than that of DBD."} {"id": "PMID:1272474", "title": "Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - I. Nucleotide composition of RNAs from the liver and tumor tissues of rats.", "content": "The characteristics of the ribonucleic acids of Guerin tumor was the subject of this work. The effect of tumor development on the structure of the ribonucleic acids in the liver of tumor bearing rats was studied. Some differences of nucleotide compositions in RNAs isolated from subcellular fractions of liver of control and tumor bearing rats and of cancer tissue were observed. The nucleotide compositions of cancer nuclear RNA is distinctly different from liver RNA. The changes in primary structure of liver RNAs due by development of tumor in rats may be result of metabolic peculiarities of these RNAs.", "contents": "Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - I. Nucleotide composition of RNAs from the liver and tumor tissues of rats. The characteristics of the ribonucleic acids of Guerin tumor was the subject of this work. The effect of tumor development on the structure of the ribonucleic acids in the liver of tumor bearing rats was studied. Some differences of nucleotide compositions in RNAs isolated from subcellular fractions of liver of control and tumor bearing rats and of cancer tissue were observed. The nucleotide compositions of cancer nuclear RNA is distinctly different from liver RNA. The changes in primary structure of liver RNAs due by development of tumor in rats may be result of metabolic peculiarities of these RNAs."} {"id": "PMID:1272475", "title": "Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - II. metabolic peculiarities of RNAs from the liver and tumor tissues of rats.", "content": "Metabolic peculiarities of RNAs in the liver of the tumor bearing and in the tumor tissue were found. The synthesis of nuclear RNA in liver of tumor bearing rats is distinctly disordered in comparison to that of control rats. The level of 14C-orotic acid incorporation into RNA of cancer tissue is manifold lower than that into the liver RNA. The studies on turnover rate showed the metabolic heterogeneity of the nuclear RNAs. The part of them showed a short turnover, the other RNAs were degraded much slower.", "contents": "Structural and metabolic characterization of RNAs from rats with experimental Guerin tumor - II. metabolic peculiarities of RNAs from the liver and tumor tissues of rats. Metabolic peculiarities of RNAs in the liver of the tumor bearing and in the tumor tissue were found. The synthesis of nuclear RNA in liver of tumor bearing rats is distinctly disordered in comparison to that of control rats. The level of 14C-orotic acid incorporation into RNA of cancer tissue is manifold lower than that into the liver RNA. The studies on turnover rate showed the metabolic heterogeneity of the nuclear RNAs. The part of them showed a short turnover, the other RNAs were degraded much slower."} {"id": "PMID:1272476", "title": "Serum immunoglobulin levels in cancer patients. II. Serum immunoglobulins and stage of tumor progress.", "content": "A study of the IgG, IgA and IgM levels in relation with the clinical course of the tumor disorders revealed the IgG values to correlate with the progress of the disease. Their levels were found to rise from stage I to stage III of the classification according to tumor progress, the difference between these stages being of statistical significance. A similar trend, though statistically nonsignificant, was noted also in IgA levels, but these proved right from the start to be higher than the values reported for the apparent normal population. The rising tendency in the IgG--and the less striking one in the IgA levels were also confirmed by a comparison of the mean values of collections separated by a definite time interval in the same patients and this both for the deteriorated and unchanged cases, but not for the group of improved patients.", "contents": "Serum immunoglobulin levels in cancer patients. II. Serum immunoglobulins and stage of tumor progress. A study of the IgG, IgA and IgM levels in relation with the clinical course of the tumor disorders revealed the IgG values to correlate with the progress of the disease. Their levels were found to rise from stage I to stage III of the classification according to tumor progress, the difference between these stages being of statistical significance. A similar trend, though statistically nonsignificant, was noted also in IgA levels, but these proved right from the start to be higher than the values reported for the apparent normal population. The rising tendency in the IgG--and the less striking one in the IgA levels were also confirmed by a comparison of the mean values of collections separated by a definite time interval in the same patients and this both for the deteriorated and unchanged cases, but not for the group of improved patients."} {"id": "PMID:1272543", "title": "Reorganizing the nursing home industry: a proposal.", "content": "This paper proposes a reorganization of the nursing home industry with capital facilities owned by government, but with management conducted through a system of competitive contracts with the private sector. The paper explicity demonstrates in real estate finance terms how the present system of private ownership of capital facilities inherently impedes providing a high quality of care. The authors believe that in the proposed industry reorganization, market forces, instead of working against quality care, would be supportive of quality care in a framework that would involve generally less regulation than exists today.", "contents": "Reorganizing the nursing home industry: a proposal. This paper proposes a reorganization of the nursing home industry with capital facilities owned by government, but with management conducted through a system of competitive contracts with the private sector. The paper explicity demonstrates in real estate finance terms how the present system of private ownership of capital facilities inherently impedes providing a high quality of care. The authors believe that in the proposed industry reorganization, market forces, instead of working against quality care, would be supportive of quality care in a framework that would involve generally less regulation than exists today."} {"id": "PMID:1272544", "title": "Food distribution as a guarantee for nutrition and health: China's experience.", "content": "In China, agriculture, health, education, and welfare are intricately woven as part of the development and its relationship to health programs, the strategy of food rationing and the \"private plot\" to improve nutrition and health, and the balance of food and population in the Chinese society. China's nutritional experience contributes significantly to understanding the role of \"energy food\" in the struggle against protein malnutrition and hunger. The author has outlined the implications for the developing countries.", "contents": "Food distribution as a guarantee for nutrition and health: China's experience. In China, agriculture, health, education, and welfare are intricately woven as part of the development and its relationship to health programs, the strategy of food rationing and the \"private plot\" to improve nutrition and health, and the balance of food and population in the Chinese society. China's nutritional experience contributes significantly to understanding the role of \"energy food\" in the struggle against protein malnutrition and hunger. The author has outlined the implications for the developing countries."} {"id": "PMID:1272545", "title": "The impact of certificate-of need controls on hospital investment.", "content": "Certificate-of-Need (CON) controls over hospital investment have been enacted by a number of states in recent years and the National Health Planning and Resources Development Act of 1974 provides strong incentives for adoption of CON in additional states. In this study, we review the questions that have been raised about the effectiveness of CON controls and then we develop quantitative estimates of the impact of CON on investment. These estimates show that CON did not reduce the total dollar volume of investment but altered its composition, retarding expansion in bed supplies but increasing investment in new services and equipment. We suggest that this finding may be due to (1) the emphasis in CON laws and programs on controlling bed supplies and (2) a substitution of new services and equipment for additional beds in response to financial factors and organizational pressures for expansion. Finally, we caution against the conslusion that CON controls should be broadened and tightened, though our results might be so interpreted, because of the practical difficulties involved in reviewing and certifying large numbers of small investment projects.", "contents": "The impact of certificate-of need controls on hospital investment. Certificate-of-Need (CON) controls over hospital investment have been enacted by a number of states in recent years and the National Health Planning and Resources Development Act of 1974 provides strong incentives for adoption of CON in additional states. In this study, we review the questions that have been raised about the effectiveness of CON controls and then we develop quantitative estimates of the impact of CON on investment. These estimates show that CON did not reduce the total dollar volume of investment but altered its composition, retarding expansion in bed supplies but increasing investment in new services and equipment. We suggest that this finding may be due to (1) the emphasis in CON laws and programs on controlling bed supplies and (2) a substitution of new services and equipment for additional beds in response to financial factors and organizational pressures for expansion. Finally, we caution against the conslusion that CON controls should be broadened and tightened, though our results might be so interpreted, because of the practical difficulties involved in reviewing and certifying large numbers of small investment projects."} {"id": "PMID:1272594", "title": "Thrombokinetics in systemic lupus erythematosus A preliminary report.", "content": "Twelve non-thrombocytopenic patients ( 3 males and 9 females) with systemic lupus erythematosus (SLE) were investigated with respect to platelet size, percentage of megathrombocytes, platelet survival and platelet production. The values for platelet size and percentage of megathrombocytes did not differ from those of a control group. In the SLE group the mean platelet MLS was identical to the control mean, and all patients with SLE had values for platelet MLS within the range of the control subjects. All SLE patients but one had values for platelet turnover within the control range. For unclear reason one single SLE patient had a moderately elevated platelet turnover value. The results of the present investigation do not support the theory that a state of compensated thrombocytolysis is present in SLE.", "contents": "Thrombokinetics in systemic lupus erythematosus A preliminary report. Twelve non-thrombocytopenic patients ( 3 males and 9 females) with systemic lupus erythematosus (SLE) were investigated with respect to platelet size, percentage of megathrombocytes, platelet survival and platelet production. The values for platelet size and percentage of megathrombocytes did not differ from those of a control group. In the SLE group the mean platelet MLS was identical to the control mean, and all patients with SLE had values for platelet MLS within the range of the control subjects. All SLE patients but one had values for platelet turnover within the control range. For unclear reason one single SLE patient had a moderately elevated platelet turnover value. The results of the present investigation do not support the theory that a state of compensated thrombocytolysis is present in SLE."} {"id": "PMID:1272595", "title": "On the phosphate problem.", "content": "Acceptable Daily Intakes (ADI) of phosphorus set by the FAO/WHO Committee are fixed at 70 and 30 mg P/kg body weight, for conditional (C) (where Ca intake is high) and unconditional (UC) intake, respectively. In light of the increasing application of phosphates in food industries, the question arises whether these permissible limits are not exceeded by certain population group (s). The groups studied in this paper included: children, nursing mothers, farmers and town's men, and students. Average per capita and excessive consumptions were also estimated. Spectrometric techniques were used for analysis of both phosphorus and calcium. Unless for few items, Dutch Food Composition Tables were found accurate enough to use for calculations. Intake of P was found to exceed the UC ADI in most groups, and even the C ADI in infants (1 year). Food intakes of all groups resulted in P/Ca ratios higher than the recommended dietary allowances of U.S.A. Milk and dairy products proved important items for lowering this ratio in the Dutch diet. It is concluded that more investigation for the toxicological evaluation of phosphates is required, and a more clear ADI need be set. Food laws must take into account addition of phosphates during food processing. Estimation of P intake should be carried out particularly in countries of low calcium intake or high consumption of phosphate-treated or phosphate-rich foods (e.g. wholemeal bread and nut consumption in Iran).", "contents": "On the phosphate problem. Acceptable Daily Intakes (ADI) of phosphorus set by the FAO/WHO Committee are fixed at 70 and 30 mg P/kg body weight, for conditional (C) (where Ca intake is high) and unconditional (UC) intake, respectively. In light of the increasing application of phosphates in food industries, the question arises whether these permissible limits are not exceeded by certain population group (s). The groups studied in this paper included: children, nursing mothers, farmers and town's men, and students. Average per capita and excessive consumptions were also estimated. Spectrometric techniques were used for analysis of both phosphorus and calcium. Unless for few items, Dutch Food Composition Tables were found accurate enough to use for calculations. Intake of P was found to exceed the UC ADI in most groups, and even the C ADI in infants (1 year). Food intakes of all groups resulted in P/Ca ratios higher than the recommended dietary allowances of U.S.A. Milk and dairy products proved important items for lowering this ratio in the Dutch diet. It is concluded that more investigation for the toxicological evaluation of phosphates is required, and a more clear ADI need be set. Food laws must take into account addition of phosphates during food processing. Estimation of P intake should be carried out particularly in countries of low calcium intake or high consumption of phosphate-treated or phosphate-rich foods (e.g. wholemeal bread and nut consumption in Iran)."} {"id": "PMID:1272596", "title": "Effect of electrical stimulation of the medullary respiratory neurons on respiratory air flow in cats. New findings on expiratory neurons.", "content": "Respiratory air flow during electrical stimulation of the medullary respiratory neurons was measured in 25 sodium pentobarbital-anesthetized cats. The effect of variation of stimulus parameters on the air flow was studied too. The medullary respiratory neurons were localized by exploring the medulla with microelectrodes. The inspiratory neurons were found hetween 2 and 4 mm lateral to the midline, and from the level of the obex to 4 mm rostrally in the ventral reticular formation. The expiratory cells were between 2 and 3 mm lateral to the midline, extending from the level of the obex to 3 mm caudally, slightly less ventral than the inspiratory neurons. The maximal inspiratory and expiratory flow rates were 56 and 44 liters per minute respectively when the respiratory neurons were stimulated with a stimulus of 4 volts and 200 Hz/sec., while duration of the stimulating pulse was 0.5 millisecond. In general, the increase in air flow was proportional to the magnitude of the stimulus strength, stimulus frequency and duration of the stimulating pulse.", "contents": "Effect of electrical stimulation of the medullary respiratory neurons on respiratory air flow in cats. New findings on expiratory neurons. Respiratory air flow during electrical stimulation of the medullary respiratory neurons was measured in 25 sodium pentobarbital-anesthetized cats. The effect of variation of stimulus parameters on the air flow was studied too. The medullary respiratory neurons were localized by exploring the medulla with microelectrodes. The inspiratory neurons were found hetween 2 and 4 mm lateral to the midline, and from the level of the obex to 4 mm rostrally in the ventral reticular formation. The expiratory cells were between 2 and 3 mm lateral to the midline, extending from the level of the obex to 3 mm caudally, slightly less ventral than the inspiratory neurons. The maximal inspiratory and expiratory flow rates were 56 and 44 liters per minute respectively when the respiratory neurons were stimulated with a stimulus of 4 volts and 200 Hz/sec., while duration of the stimulating pulse was 0.5 millisecond. In general, the increase in air flow was proportional to the magnitude of the stimulus strength, stimulus frequency and duration of the stimulating pulse."} {"id": "PMID:1272597", "title": "Leg lengthening with a new type of external fixator (a preliminary report on 24 cases).", "content": "A new type of external fixator bas been designed for absolute fixation and prevention of lateral migration of fragments of bone. The apparatus has been used for leg lengthening. The apparatus and the technique are described and results of the first 24 cases are presented. Complications were minimal. The technique proved to be simple to apply, and painless to the patient with his ambulation from the start. And less expense are involved because of a very short period of hospitalization.", "contents": "Leg lengthening with a new type of external fixator (a preliminary report on 24 cases). A new type of external fixator bas been designed for absolute fixation and prevention of lateral migration of fragments of bone. The apparatus has been used for leg lengthening. The apparatus and the technique are described and results of the first 24 cases are presented. Complications were minimal. The technique proved to be simple to apply, and painless to the patient with his ambulation from the start. And less expense are involved because of a very short period of hospitalization."} {"id": "PMID:1272599", "title": "Progeria, a case report from Iran.", "content": "A 4 1/4-year-old male child with the Hutchinson-Gilford progeria syndrome is described. This is the first case to be reported from Iran.", "contents": "Progeria, a case report from Iran. A 4 1/4-year-old male child with the Hutchinson-Gilford progeria syndrome is described. This is the first case to be reported from Iran."} {"id": "PMID:1272602", "title": "A process model for curriculum deveopment.", "content": "An operational model of the processes of decision making in the development of curriculum was porposed. Attempts were made to present a conceptual framework from which the model was elaborated. In addition, examples of field experience related to the application of educational planning theory into practive were presented.", "contents": "A process model for curriculum deveopment. An operational model of the processes of decision making in the development of curriculum was porposed. Attempts were made to present a conceptual framework from which the model was elaborated. In addition, examples of field experience related to the application of educational planning theory into practive were presented."} {"id": "PMID:1272617", "title": "Convulsive seizures in infancy and childhood.", "content": "Epilepsy is a symptom and not a disease. An etiologic and therapeutic approach to the acutely convulsing child has been outlined. The necessity of attempting to determine the cause while in the process of stopping the seizure has been emphasized. Suggestions as to what to evaluate on physical examination and what laboratory tests to order have been discussed. An approach to the child whose seizure was not witnessed by a physician is also presented. Emphasis is placed on obtaining an accurate history. Finally, the treatment of a child with epilepsy involves more than prescribing appropriate medication. The child's performance in school and the concerns of parents and patient must be considered.", "contents": "Convulsive seizures in infancy and childhood. Epilepsy is a symptom and not a disease. An etiologic and therapeutic approach to the acutely convulsing child has been outlined. The necessity of attempting to determine the cause while in the process of stopping the seizure has been emphasized. Suggestions as to what to evaluate on physical examination and what laboratory tests to order have been discussed. An approach to the child whose seizure was not witnessed by a physician is also presented. Emphasis is placed on obtaining an accurate history. Finally, the treatment of a child with epilepsy involves more than prescribing appropriate medication. The child's performance in school and the concerns of parents and patient must be considered."} {"id": "PMID:1272622", "title": "Echocardiographic assessment of cor pulmonale in cystic fibrosis.", "content": "The early clinical recognition and assessment of cor pulmonale are frequently difficult. To evaluate the usefulness of echocardiographic measurement of right ventricular dimension and septal motion in assessing cor pulmonale, we studied 94 patients with cystic fibrosis of varying severity. There was a significant relationship between increasing right ventricular dimension index (RVDI) and (1) decreasing clinical score, vital capacity, forced expiratory volume in one second (FEV1), and maximal midexpiratory flow rate (MMFR); and (2) increasing residual volume and thoracic gas volume. There was no correlation between right ventricular dimension index and PaO2. These findings were supported by electrocardiogram and pathologic evidence of right ventricular involvement. Abnormal septal motion was observed more frequently in patients with severe obstructive airway disease as measured by decreased vital capacity, FEV1, and MMFR. The data show that there is echocardiographic evidence of mild right ventricular enlargement and/or hypertrophy much earlier in the course of cystic fibrosis than previously suspected and that the echocardiogram is a useful tool in the evaluation of cor pulmonale in patients with cystic fibrosis.", "contents": "Echocardiographic assessment of cor pulmonale in cystic fibrosis. The early clinical recognition and assessment of cor pulmonale are frequently difficult. To evaluate the usefulness of echocardiographic measurement of right ventricular dimension and septal motion in assessing cor pulmonale, we studied 94 patients with cystic fibrosis of varying severity. There was a significant relationship between increasing right ventricular dimension index (RVDI) and (1) decreasing clinical score, vital capacity, forced expiratory volume in one second (FEV1), and maximal midexpiratory flow rate (MMFR); and (2) increasing residual volume and thoracic gas volume. There was no correlation between right ventricular dimension index and PaO2. These findings were supported by electrocardiogram and pathologic evidence of right ventricular involvement. Abnormal septal motion was observed more frequently in patients with severe obstructive airway disease as measured by decreased vital capacity, FEV1, and MMFR. The data show that there is echocardiographic evidence of mild right ventricular enlargement and/or hypertrophy much earlier in the course of cystic fibrosis than previously suspected and that the echocardiogram is a useful tool in the evaluation of cor pulmonale in patients with cystic fibrosis."} {"id": "PMID:1272625", "title": "Hydantoin-5-propionic aciduria in folic acid nondependent formiminoglutamic aciduria observed in two siblings.", "content": "Hydantion-5-propionic acid was detected in massive amounts in the urine of two previously described sisters with folic acid nondependent formiminoglutamic aciduria. HPA was identified rigorously, e.g. by gas chromatography-mass spectrometry, and was measured quantitatively by selected ion monitoring (mass fragmentography) using deuterated HPA as internal standard. Before histidine loading, both girls with the postulated formiminotransferase deficiency excreted an amount of HPA more than 50 times greater than the control subjects. After histidine ingestion, HPA excretion was still doubled or tripled. With the exception of the father, the values for the other members of the family also markedly exceeded the normal range and were of the same order of magnitude as in folate deficiency. Measurement of HPA excretion in urine seems to be a valuable supplement or alternative to the enzymatic FIGu test for the detection of general or functional folate deficiency or impaired folate utilization and it will be indispensable for the detection of (as yet unknown) 4-imidazolone-5-propionic acid hydrolase deficiency.", "contents": "Hydantoin-5-propionic aciduria in folic acid nondependent formiminoglutamic aciduria observed in two siblings. Hydantion-5-propionic acid was detected in massive amounts in the urine of two previously described sisters with folic acid nondependent formiminoglutamic aciduria. HPA was identified rigorously, e.g. by gas chromatography-mass spectrometry, and was measured quantitatively by selected ion monitoring (mass fragmentography) using deuterated HPA as internal standard. Before histidine loading, both girls with the postulated formiminotransferase deficiency excreted an amount of HPA more than 50 times greater than the control subjects. After histidine ingestion, HPA excretion was still doubled or tripled. With the exception of the father, the values for the other members of the family also markedly exceeded the normal range and were of the same order of magnitude as in folate deficiency. Measurement of HPA excretion in urine seems to be a valuable supplement or alternative to the enzymatic FIGu test for the detection of general or functional folate deficiency or impaired folate utilization and it will be indispensable for the detection of (as yet unknown) 4-imidazolone-5-propionic acid hydrolase deficiency."} {"id": "PMID:1272626", "title": "Ornithine decarboxylase activity in human fetal liver.", "content": "The Km of ODC in human fetal liver is comparable with values obtained in other tissues and species (3.3 X 10(-4) M). The ODC activity in human fetal liver varies with the gestational age of the fetus, declining rapidly from a peak in the youngest tissue examined. Human fetal liver explants maintained in organ culture for 32 hr demonstrate no ODC activity in the presence or absence of insulin. Rat fetal liver explants display a prolonged period of stable ODC activity after 16 hr in organ culture.", "contents": "Ornithine decarboxylase activity in human fetal liver. The Km of ODC in human fetal liver is comparable with values obtained in other tissues and species (3.3 X 10(-4) M). The ODC activity in human fetal liver varies with the gestational age of the fetus, declining rapidly from a peak in the youngest tissue examined. Human fetal liver explants maintained in organ culture for 32 hr demonstrate no ODC activity in the presence or absence of insulin. Rat fetal liver explants display a prolonged period of stable ODC activity after 16 hr in organ culture."} {"id": "PMID:1272627", "title": "Gaseous exchange and acid-base balance in premature lambs during liquid ventilation since birth.", "content": "Nine distressed premature lambs were studied before, during, and after ventilation with fluorocarbon liquid (FC-80). It was found that premature lambs, delivered by cesarean section, could be adequately ventilated with oxygenated liquid for period up to 3 hr. Using fluarocarbon liquid in conjunction with the described liquid breathing system, it was possible to maintain remarkably good pulmonary gas exchange and acid-base balance during normothermic conditions. In addition, peak intratracheal pressures measured during recovery from liquid ventilation were significanly reduced (P is less than 0.001) as compared with preliquid ventilation values. This improvement in lung function is in direct contrast to the deterioration in that of the adult animal following liquid ventilation as reported previously.", "contents": "Gaseous exchange and acid-base balance in premature lambs during liquid ventilation since birth. Nine distressed premature lambs were studied before, during, and after ventilation with fluorocarbon liquid (FC-80). It was found that premature lambs, delivered by cesarean section, could be adequately ventilated with oxygenated liquid for period up to 3 hr. Using fluarocarbon liquid in conjunction with the described liquid breathing system, it was possible to maintain remarkably good pulmonary gas exchange and acid-base balance during normothermic conditions. In addition, peak intratracheal pressures measured during recovery from liquid ventilation were significanly reduced (P is less than 0.001) as compared with preliquid ventilation values. This improvement in lung function is in direct contrast to the deterioration in that of the adult animal following liquid ventilation as reported previously."} {"id": "PMID:1272628", "title": "Lactate and pyruvate as fetal metabolic substrates.", "content": "Lactate and pyruvate concentration differences across the fetal umbilical circulation and the maternal uterine circulation were measured in a chronic sheep preparation. Significant gains in lactate in both the fetal and maternal circulations were observed. The lactate taken up by the fetus would account for 32% of fetal oxygen consumption if oxidized. There was no significant change in pyruvate concentration across the fetal umbilical circulation; however, pyruvate was gained by maternal uterine blood.", "contents": "Lactate and pyruvate as fetal metabolic substrates. Lactate and pyruvate concentration differences across the fetal umbilical circulation and the maternal uterine circulation were measured in a chronic sheep preparation. Significant gains in lactate in both the fetal and maternal circulations were observed. The lactate taken up by the fetus would account for 32% of fetal oxygen consumption if oxidized. There was no significant change in pyruvate concentration across the fetal umbilical circulation; however, pyruvate was gained by maternal uterine blood."} {"id": "PMID:1272629", "title": "Elevated plasma levels of carcinoembryonic antigen in cystic fibrosis.", "content": "Elevated levels of plasma CEA were found in patients with cystic fibrosis. The elevations were well correlated with the Shwachman scores of the patients. Parallel changes of the levels of plasma CEA and clinical conditions of four patients were also observed in the follow-up studies. Close clinical examination indicated that the elevated plasma CEA of cystic fibrosis patients may be derived from sputum which is produced in abnormal amounts. This hypothesis is further supported by the very high content and the chromatographic profile of the CEA activity of sputum from patients with cystic fibrosis.", "contents": "Elevated plasma levels of carcinoembryonic antigen in cystic fibrosis. Elevated levels of plasma CEA were found in patients with cystic fibrosis. The elevations were well correlated with the Shwachman scores of the patients. Parallel changes of the levels of plasma CEA and clinical conditions of four patients were also observed in the follow-up studies. Close clinical examination indicated that the elevated plasma CEA of cystic fibrosis patients may be derived from sputum which is produced in abnormal amounts. This hypothesis is further supported by the very high content and the chromatographic profile of the CEA activity of sputum from patients with cystic fibrosis."} {"id": "PMID:1272630", "title": "Temperature-sensitive mutants of influenza A virus: response of children to the influenza A/Hong Kong/68-ts-1(E) (H3N2) and influenza A/Udorn/72-ts-1(E) (H3N2) candidate vaccine viruses and significance of immunity to neuraminidase antigen.", "content": "One of two slightly different influenza A/ts-1[E] recombinant candidate live vaccines was given intranasally to each of 23 young children. Twelve of 15 children who had no serum HI antibody but who did have serum ANAB at the time of administration became infected and 1 had mild rhinitis. All eight who lacked both types of antibody became infected and they shed virus in higher titer and for longer than the former group; five had rhinorrhea and five had mild fever. These findings suggest that serum ANAB plays a part in modulating influenza virus infection and that the full expression of virulence of these or other attenuated influenza vaccines may be manifest only in individuals lacking both HI antibody and ANAB. These particular candidate vaccine strains appear to be attenuated for older children (who have some prior experience with influenza A as demonstrated by serum ANAB), but the occurrence of fever in over half who had no prior experience indicates that they would not be acceptable for a vaccine in wide-spread use.", "contents": "Temperature-sensitive mutants of influenza A virus: response of children to the influenza A/Hong Kong/68-ts-1(E) (H3N2) and influenza A/Udorn/72-ts-1(E) (H3N2) candidate vaccine viruses and significance of immunity to neuraminidase antigen. One of two slightly different influenza A/ts-1[E] recombinant candidate live vaccines was given intranasally to each of 23 young children. Twelve of 15 children who had no serum HI antibody but who did have serum ANAB at the time of administration became infected and 1 had mild rhinitis. All eight who lacked both types of antibody became infected and they shed virus in higher titer and for longer than the former group; five had rhinorrhea and five had mild fever. These findings suggest that serum ANAB plays a part in modulating influenza virus infection and that the full expression of virulence of these or other attenuated influenza vaccines may be manifest only in individuals lacking both HI antibody and ANAB. These particular candidate vaccine strains appear to be attenuated for older children (who have some prior experience with influenza A as demonstrated by serum ANAB), but the occurrence of fever in over half who had no prior experience indicates that they would not be acceptable for a vaccine in wide-spread use."} {"id": "PMID:1272631", "title": "Intestinal absorption of amino acids and peptides in Hartnup disorder.", "content": "Absorption of free and peptide-bound amino acids was investigated in a girl with Hartnup disorder aged 26 months. Plasma levels of amino acids were followed after oral administration of (1) an amino acid mixture simulating casein and (2) an equivalent dose of a partial enzymic hydrolysate of casein containing oligopeptides in addition to free amino acids. The results suggested that many neutral amino acids were poorly absorbed when given in the free form, but much more readily absorbed when given as peptides. Unexpectedly, the results also suggested that glutamic acid was poorly absorbed when given in the free form. The results obtained with threonine could not be interpreted. There was an increased renal clearance of many neutral amino acids, including glycine, but clearance of proline was not increased. Most amino acids with an increased renal clearance also appeared to be poorly absorbed when given by mouth in the free form.", "contents": "Intestinal absorption of amino acids and peptides in Hartnup disorder. Absorption of free and peptide-bound amino acids was investigated in a girl with Hartnup disorder aged 26 months. Plasma levels of amino acids were followed after oral administration of (1) an amino acid mixture simulating casein and (2) an equivalent dose of a partial enzymic hydrolysate of casein containing oligopeptides in addition to free amino acids. The results suggested that many neutral amino acids were poorly absorbed when given in the free form, but much more readily absorbed when given as peptides. Unexpectedly, the results also suggested that glutamic acid was poorly absorbed when given in the free form. The results obtained with threonine could not be interpreted. There was an increased renal clearance of many neutral amino acids, including glycine, but clearance of proline was not increased. Most amino acids with an increased renal clearance also appeared to be poorly absorbed when given by mouth in the free form."} {"id": "PMID:1272633", "title": "Kinetic properties of pyruvate kinase in human maternal leukocytes in fetal malnutrition.", "content": "Pyruvate kinase (PK) is one of the regulatory enzymes in glycolysis. The present study was undertaken to determine whether regulation of the enzyme by normally occurring metabolites was disturbed in leukocytes of mothers who delivered fetally malnourished (FM) babies. Kinetic studies of enzyme regulation by physiologic effectors approximated a potential regulating mechanism of the enzyme in its cellular environment. There are two isoenzymes of PK. Leukocytes contain an M2 enzyme with intermediate regulatory properties between the liver (type L) and the muscle (type M) enzymes. The presence in the cell of M2 PK in the A form leads to inhibition of glycolysis by amino acids, such as alanine, and therefore, to the sparing of glucose but probably inhibition of energy production from glucose. In this study, leukocytes were isolated from blood of six pregnant women and 11 women in the postpartum period in Oklahoma and at parturition from 31 women in Mexico. Fourteen of the latter group delivered FM babies. The kinetic characteristics of the nonpurified enzyme PK with respect to allosteric modulation in fructose-1, 6-phosphate (FDP) and L-alanine (Ala) were studied in the leukocyte extracts. Data for initial reaction velocities (v) vs substrate concentrations (s), double reciprocal Lineweaver-Burk plots, and Hill plots are presented. The equations for the double reciprocal plots were determined by linear regression analysis. The enzyme constants were derived by computer, and the values compared by the Mann-Whitney U-test. In all subjects studied, 0.5 mM FDP activated and 2 mM L-alanine inhibited the enzyme. During pregnancy, the v vs s concentration curves were hyperbolic (Hill coefficient, n is less than 1.0) except for the Ala-inhibited enzyme during pregnancy, which had a sigmoid curve, n=1.54. The interaction of FDP and Ala was dependent on the concentration of the substrate phosphoenolpyruvate (PEP) at low [PEP]. There was net activation, not inhibition, at high concentrations; the switchover was at 0.5 mM PEP during pregnancy. In Mexican mothers having normal babies (normal mothers) the maximum initial velocity, V (micromoles per min per mg of DNA), with respect to PEP, was 2.22+/-0.34; in FM mothers, V was 2.01+/-0.44. With respect to binding of the substrate, PEP, V of the leukocyte enzymes in FM mothers vs normal mothers was equally inhibited by Ala (deltaV=-50% vs -47%), but was significantly less responsive to stimulation by FDP (deltaV=+10% vs +75%). When both Ala and FDP were present, FDP less effectively overcame the inhibition by Ala (deltaV=-9% vs +54%). The K0.05 of the enzyme (molar concentration X 10(-4) PEP) was significantly reduced by FDP, whether Ala was present or not, during pregnancy and in the postpartum period in leukocytes of Oklahoma mothers and at term in Mexican mothers. The K0.5 for normal and FM mothers was similar. Thus, the enzyme in leukocytes of Mexican mothers who delivered FM and normal babies exhibited different kinetic responses to the allosteric modulators...", "contents": "Kinetic properties of pyruvate kinase in human maternal leukocytes in fetal malnutrition. Pyruvate kinase (PK) is one of the regulatory enzymes in glycolysis. The present study was undertaken to determine whether regulation of the enzyme by normally occurring metabolites was disturbed in leukocytes of mothers who delivered fetally malnourished (FM) babies. Kinetic studies of enzyme regulation by physiologic effectors approximated a potential regulating mechanism of the enzyme in its cellular environment. There are two isoenzymes of PK. Leukocytes contain an M2 enzyme with intermediate regulatory properties between the liver (type L) and the muscle (type M) enzymes. The presence in the cell of M2 PK in the A form leads to inhibition of glycolysis by amino acids, such as alanine, and therefore, to the sparing of glucose but probably inhibition of energy production from glucose. In this study, leukocytes were isolated from blood of six pregnant women and 11 women in the postpartum period in Oklahoma and at parturition from 31 women in Mexico. Fourteen of the latter group delivered FM babies. The kinetic characteristics of the nonpurified enzyme PK with respect to allosteric modulation in fructose-1, 6-phosphate (FDP) and L-alanine (Ala) were studied in the leukocyte extracts. Data for initial reaction velocities (v) vs substrate concentrations (s), double reciprocal Lineweaver-Burk plots, and Hill plots are presented. The equations for the double reciprocal plots were determined by linear regression analysis. The enzyme constants were derived by computer, and the values compared by the Mann-Whitney U-test. In all subjects studied, 0.5 mM FDP activated and 2 mM L-alanine inhibited the enzyme. During pregnancy, the v vs s concentration curves were hyperbolic (Hill coefficient, n is less than 1.0) except for the Ala-inhibited enzyme during pregnancy, which had a sigmoid curve, n=1.54. The interaction of FDP and Ala was dependent on the concentration of the substrate phosphoenolpyruvate (PEP) at low [PEP]. There was net activation, not inhibition, at high concentrations; the switchover was at 0.5 mM PEP during pregnancy. In Mexican mothers having normal babies (normal mothers) the maximum initial velocity, V (micromoles per min per mg of DNA), with respect to PEP, was 2.22+/-0.34; in FM mothers, V was 2.01+/-0.44. With respect to binding of the substrate, PEP, V of the leukocyte enzymes in FM mothers vs normal mothers was equally inhibited by Ala (deltaV=-50% vs -47%), but was significantly less responsive to stimulation by FDP (deltaV=+10% vs +75%). When both Ala and FDP were present, FDP less effectively overcame the inhibition by Ala (deltaV=-9% vs +54%). The K0.05 of the enzyme (molar concentration X 10(-4) PEP) was significantly reduced by FDP, whether Ala was present or not, during pregnancy and in the postpartum period in leukocytes of Oklahoma mothers and at term in Mexican mothers. The K0.5 for normal and FM mothers was similar. Thus, the enzyme in leukocytes of Mexican mothers who delivered FM and normal babies exhibited different kinetic responses to the allosteric modulators..."} {"id": "PMID:1272634", "title": "Response of the neonatal heart to a new inotropic agent, RO2-2985 (X537A).", "content": "The ionophore RO2-2985 did not produce a positive inotropic response in 1-day-old canine isolated ventricle. A gradual increase in inotropic response was seen with age. Isolated atria, however, exhibited a positive inotropic response at birth (50% increased dF/dt), which became progressively greater with age (100% increase in dF/dt at 15 days of age). In the neonatal heart in situ there was a positive inotropic response in 1-day-old puppies (40% increase in left ventricular dF/dt) with progressively greater responses with age (135% increase in left ventricular dF/dt at 11 days of age). There was a positive chronotropic (75-125% increase) response to RO2-2985 at all ages studied. The drug elevated systemic arterial pressure (150% increase in mean arterial pressure) to a similar degree in all ages studied. RO2-2985 depressed total calcium binding by both neonatal and adult isolated cardiac sarcoplasmic reticulum approximately 50%.", "contents": "Response of the neonatal heart to a new inotropic agent, RO2-2985 (X537A). The ionophore RO2-2985 did not produce a positive inotropic response in 1-day-old canine isolated ventricle. A gradual increase in inotropic response was seen with age. Isolated atria, however, exhibited a positive inotropic response at birth (50% increased dF/dt), which became progressively greater with age (100% increase in dF/dt at 15 days of age). In the neonatal heart in situ there was a positive inotropic response in 1-day-old puppies (40% increase in left ventricular dF/dt) with progressively greater responses with age (135% increase in left ventricular dF/dt at 11 days of age). There was a positive chronotropic (75-125% increase) response to RO2-2985 at all ages studied. The drug elevated systemic arterial pressure (150% increase in mean arterial pressure) to a similar degree in all ages studied. RO2-2985 depressed total calcium binding by both neonatal and adult isolated cardiac sarcoplasmic reticulum approximately 50%."} {"id": "PMID:1272635", "title": "Parotid gland function in children with cystic fibrosis and child control subjects.", "content": "Parotid saliva was collected from 22 children with cystic fibrosis (CF) and 21 control children. Stimulation was by 0.1 ml 5% citric acid on the tongue every 15 sec over a period of 10 min, and samples were collected for 2-min intervals. Stimulated saliva showed a lag period of low amylase release, and an activated period of higher amylase release. The major difference between CF and child control parotid saliva was in the elevated calcium concentrations in CF subjects. Flow rate and amylase, although higher in the CF group, were not raised to a statistically significant level. There were higher mean values for sodium and inorganic phosphate in CF children but statistical significance was minimal. Potassium values were almost identical in CF and control saliva. In the activated parotid saliva samples of both control and CF subjects there were positive correlations between flow rate and calcium, flow rate and sodium, anylase and calcium, and sodium and calcium, and negative correlations between sodium and potassium. The parotid function test has no value as a diagnostic test for cystic fibrosis, as even calcium values show too much overlap with control saliva to be of diagnostic worth.", "contents": "Parotid gland function in children with cystic fibrosis and child control subjects. Parotid saliva was collected from 22 children with cystic fibrosis (CF) and 21 control children. Stimulation was by 0.1 ml 5% citric acid on the tongue every 15 sec over a period of 10 min, and samples were collected for 2-min intervals. Stimulated saliva showed a lag period of low amylase release, and an activated period of higher amylase release. The major difference between CF and child control parotid saliva was in the elevated calcium concentrations in CF subjects. Flow rate and amylase, although higher in the CF group, were not raised to a statistically significant level. There were higher mean values for sodium and inorganic phosphate in CF children but statistical significance was minimal. Potassium values were almost identical in CF and control saliva. In the activated parotid saliva samples of both control and CF subjects there were positive correlations between flow rate and calcium, flow rate and sodium, anylase and calcium, and sodium and calcium, and negative correlations between sodium and potassium. The parotid function test has no value as a diagnostic test for cystic fibrosis, as even calcium values show too much overlap with control saliva to be of diagnostic worth."} {"id": "PMID:1272636", "title": "Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency.", "content": "Biochemical and morphologic studies on a patient with homocystinuria due to a deficiency of 5, 10-methylenetetrahydrofolate reductase (EC. 1.1.1.68) were performed. The concentrations of homocystine in the patient's plasma and urine were 2.97 mumol/dl and 44.67 mumol/24 hr, respectively. Activities of 5, 10-methylenetetrahydrofolate reductase (expressed as nanomoles of formaldehyde formed per hr per mg of protein) in cultured skin fibroblasts and liver tissue were 0.53 (control: 5.14) and 0.00 (control: 13.80), respectively. The major abnormalities were found in the arterial bed, consisting of intimal hyperplasia, fragmentation, and disruption of elastic lamellae and subcellular changes in the endothelial cells. Extensive thrombosis was observed. The brain and the liver also showed widespread pathologic changes. In the former, neuronal loss and cellular damage were prominent and extensive. Diffuse demyelination with moderate astrocytosis was found; but demyelination was out of proportion to the vascular changes. Hirano bodies in the cortical neurons and crystalline and lamellar bodies in the Purkinje cells were observed. In the liver, there were fatty change and mild to moderate portal fibrosis. Bizarre, giant mitochondria and membrane-bound multivesicular bodies were found. Mild pathologic changes were also observed in the striated muscles and the kidneys. Focal fragmentation, disruption, and smearing of the Z discs and disorganization of the myofilaments were found in the skeletal muscles. The kidneys showed shrunken glomeruli, thickened basement membranes, and swelling of epithelial as well as endothelial cells.", "contents": "Morphologic studies in a patient with homocystinuria due to 5, 10-methylenetetrahydrofolate reductase deficiency. Biochemical and morphologic studies on a patient with homocystinuria due to a deficiency of 5, 10-methylenetetrahydrofolate reductase (EC. 1.1.1.68) were performed. The concentrations of homocystine in the patient's plasma and urine were 2.97 mumol/dl and 44.67 mumol/24 hr, respectively. Activities of 5, 10-methylenetetrahydrofolate reductase (expressed as nanomoles of formaldehyde formed per hr per mg of protein) in cultured skin fibroblasts and liver tissue were 0.53 (control: 5.14) and 0.00 (control: 13.80), respectively. The major abnormalities were found in the arterial bed, consisting of intimal hyperplasia, fragmentation, and disruption of elastic lamellae and subcellular changes in the endothelial cells. Extensive thrombosis was observed. The brain and the liver also showed widespread pathologic changes. In the former, neuronal loss and cellular damage were prominent and extensive. Diffuse demyelination with moderate astrocytosis was found; but demyelination was out of proportion to the vascular changes. Hirano bodies in the cortical neurons and crystalline and lamellar bodies in the Purkinje cells were observed. In the liver, there were fatty change and mild to moderate portal fibrosis. Bizarre, giant mitochondria and membrane-bound multivesicular bodies were found. Mild pathologic changes were also observed in the striated muscles and the kidneys. Focal fragmentation, disruption, and smearing of the Z discs and disorganization of the myofilaments were found in the skeletal muscles. The kidneys showed shrunken glomeruli, thickened basement membranes, and swelling of epithelial as well as endothelial cells."} {"id": "PMID:1272637", "title": "Effects of calcium on intestinal mucin: implications for cystic fibrosis.", "content": "A major feature of the disease cystic fibrosis is the excessive concentration of mucus within ducts and glands of mucous-producing organs. Some mucous secretions also show an elevation in calcium concentration. Using purified rat intestinal goblet cell mucin as a model mucin, we have investigated the effect of millimolar additions (1-25 mM) of CaCl2 on the physical properties of the mucin. Isotonicity of incubation media was preserved in order to mimic in vivo conditions. CaCl2 (8-15mM) caused a 15-33% decrease in viscosity, no change in electrophoretic mobility in acrylamide gels, and a 20-30% decrease in solubility of the mucin. Solubility changes were reversed by the addition of EDTA (20 mM) to incubations. Insolubility was also produced in incubations of mucin with a mixture of soluble intestinal contents (NaCl washings). These findings strongly suggest that the mucin became smaller and more dense as calcium was added, a process most probably achieved by loss of intramolecular water.", "contents": "Effects of calcium on intestinal mucin: implications for cystic fibrosis. A major feature of the disease cystic fibrosis is the excessive concentration of mucus within ducts and glands of mucous-producing organs. Some mucous secretions also show an elevation in calcium concentration. Using purified rat intestinal goblet cell mucin as a model mucin, we have investigated the effect of millimolar additions (1-25 mM) of CaCl2 on the physical properties of the mucin. Isotonicity of incubation media was preserved in order to mimic in vivo conditions. CaCl2 (8-15mM) caused a 15-33% decrease in viscosity, no change in electrophoretic mobility in acrylamide gels, and a 20-30% decrease in solubility of the mucin. Solubility changes were reversed by the addition of EDTA (20 mM) to incubations. Insolubility was also produced in incubations of mucin with a mixture of soluble intestinal contents (NaCl washings). These findings strongly suggest that the mucin became smaller and more dense as calcium was added, a process most probably achieved by loss of intramolecular water."} {"id": "PMID:1272638", "title": "Sickle cell syndromes. I. Hemoglobin SC-alpha-thalassemia.", "content": "Hematologic and globin synthesis studies were performed in a black American family in which the genes for alpha-thalassemia and hemoglobins (Hb) S and C were segregating. The following distribution of these abnormalities was found: father, sickle cell trait + alpha-thalassemia; mother, HbC trait + alpha-thalassemia, propositus, HbSC + alpha-thalassemia; older sibling, alpha-thalassemia trait; and younger sibling, hemoglobin H disease. The child with HbSC-alpha-thalassemia demonstrated more severe anemia and a more hemolytic picture than is typical of HbSC disease. Her erythrocytes exhibited decreased osmotic fragility in comparison with HbSC erythrocytes, but had an indistinguishable oxygen equilibrium curve and 2, 3-diphosphoglycerate (2, 3-DPG) level. Erythrocyte sickling in the patient, however, was significantly reduced, with less than 35% sickle forms observed at nearly complete oxygen desaturation. The sibling with hemoglobin H disease exhibited 26% Bart's (gamma4) hemoglobin at birth, a level comparable with that seen in infants with HbH disease in Far Eastern populations. At age 5 months typical findings of mild hemoglobin H disease appeared, with HbH making up 6.5% of the total hemoglobin.", "contents": "Sickle cell syndromes. I. Hemoglobin SC-alpha-thalassemia. Hematologic and globin synthesis studies were performed in a black American family in which the genes for alpha-thalassemia and hemoglobins (Hb) S and C were segregating. The following distribution of these abnormalities was found: father, sickle cell trait + alpha-thalassemia; mother, HbC trait + alpha-thalassemia, propositus, HbSC + alpha-thalassemia; older sibling, alpha-thalassemia trait; and younger sibling, hemoglobin H disease. The child with HbSC-alpha-thalassemia demonstrated more severe anemia and a more hemolytic picture than is typical of HbSC disease. Her erythrocytes exhibited decreased osmotic fragility in comparison with HbSC erythrocytes, but had an indistinguishable oxygen equilibrium curve and 2, 3-diphosphoglycerate (2, 3-DPG) level. Erythrocyte sickling in the patient, however, was significantly reduced, with less than 35% sickle forms observed at nearly complete oxygen desaturation. The sibling with hemoglobin H disease exhibited 26% Bart's (gamma4) hemoglobin at birth, a level comparable with that seen in infants with HbH disease in Far Eastern populations. At age 5 months typical findings of mild hemoglobin H disease appeared, with HbH making up 6.5% of the total hemoglobin."} {"id": "PMID:1272639", "title": "Enzymatic diagnosis and carrier detection of aspartylglucosaminuria using blood samples.", "content": "The activity of the glycoprotein degrading lysosomal hydrolase, 4-L-aspartylglycosylamine amido hydrolase (AAD Gase, EC.3.5.1.26), was measured in plasma, buffy coat leukocytes, and separated lymphocytes (Ficoll separation) from 16 patients with aspartylglucosaminuria (AGU), 29 obligate heterozygotes, and 30 control subjects. In lymphocytes the AGU patients had unmeasurable or minimal AAD Gase activity with a mean of 3.9 U. The obligate heterozygotes showed AAD Gase activities ranging from 5 to 69 U with a mean of 34.1 U. Enzyme activities in the control group ranged from 91 to 243 U with a mean of 127.9 U, and were clearly separated from the values of the heterozygotes. In leukocytes the AGU patients had unmeasurable enzyme activity and obligate heterozygotes had enzyme levels closely similar to those in the lymphocytes from the same individuals. The AAD Gase activity in the leukocytes of the control group displayed a much wider variation than in the lymphocytes, ranging from 22 to 132 U with a mean of 70.7 U. In plasma the AGU patients had undetectable AAD Gase activity. The mean enzyme level of obligate heterozygotes was 72.2 U and that of control individuals 107.2 U, but the overlap between the groups was extensive. The results indicate that homozygous deficiency of AAD Gase, i.e., aspartylglucosaminuria can be reliably diagnosed using plasma, leukocytes, or separated lymphocytes. For carrier detection only separated lymphocytes allow a satisfactory differentiation between heterozygous and normal individuals. A group of 31 siblings of verified AGU cases and 11 children of identified carriers, whose spouses had normal AAD Gase activity, were investigated using the lymphocyte assay. The observed and expected frequencies (on the basis of Mendelian probabilities) were closely similar, suggesting that the lymphocyte assay can be used reliably for carrier detection.", "contents": "Enzymatic diagnosis and carrier detection of aspartylglucosaminuria using blood samples. The activity of the glycoprotein degrading lysosomal hydrolase, 4-L-aspartylglycosylamine amido hydrolase (AAD Gase, EC.3.5.1.26), was measured in plasma, buffy coat leukocytes, and separated lymphocytes (Ficoll separation) from 16 patients with aspartylglucosaminuria (AGU), 29 obligate heterozygotes, and 30 control subjects. In lymphocytes the AGU patients had unmeasurable or minimal AAD Gase activity with a mean of 3.9 U. The obligate heterozygotes showed AAD Gase activities ranging from 5 to 69 U with a mean of 34.1 U. Enzyme activities in the control group ranged from 91 to 243 U with a mean of 127.9 U, and were clearly separated from the values of the heterozygotes. In leukocytes the AGU patients had unmeasurable enzyme activity and obligate heterozygotes had enzyme levels closely similar to those in the lymphocytes from the same individuals. The AAD Gase activity in the leukocytes of the control group displayed a much wider variation than in the lymphocytes, ranging from 22 to 132 U with a mean of 70.7 U. In plasma the AGU patients had undetectable AAD Gase activity. The mean enzyme level of obligate heterozygotes was 72.2 U and that of control individuals 107.2 U, but the overlap between the groups was extensive. The results indicate that homozygous deficiency of AAD Gase, i.e., aspartylglucosaminuria can be reliably diagnosed using plasma, leukocytes, or separated lymphocytes. For carrier detection only separated lymphocytes allow a satisfactory differentiation between heterozygous and normal individuals. A group of 31 siblings of verified AGU cases and 11 children of identified carriers, whose spouses had normal AAD Gase activity, were investigated using the lymphocyte assay. The observed and expected frequencies (on the basis of Mendelian probabilities) were closely similar, suggesting that the lymphocyte assay can be used reliably for carrier detection."} {"id": "PMID:1272677", "title": "Alpha brain wave production as an interpolated task in a Brown-Peterson paradigm.", "content": "Rehearsal, backward counting, and production of alpha brain-waves were used as interpolated tasks in a Brown-Peterson paradigm to determine their effect upon verbal retention. A within-subjects design was used in which trained subjects were told on a given trial either to produce alpha rhythm, mentally rehearse, or count backward following presentation of a CCC trigram. Results for the backward-counting condition duplicate, for the retention intervals used, the shape of the classic Peterson and Peterson forgetting curve but indicate little loss of memory in either the rehearsal or alpha conditions. No siginificant difference was found between the alpha production and rehearsal conditions.", "contents": "Alpha brain wave production as an interpolated task in a Brown-Peterson paradigm. Rehearsal, backward counting, and production of alpha brain-waves were used as interpolated tasks in a Brown-Peterson paradigm to determine their effect upon verbal retention. A within-subjects design was used in which trained subjects were told on a given trial either to produce alpha rhythm, mentally rehearse, or count backward following presentation of a CCC trigram. Results for the backward-counting condition duplicate, for the retention intervals used, the shape of the classic Peterson and Peterson forgetting curve but indicate little loss of memory in either the rehearsal or alpha conditions. No siginificant difference was found between the alpha production and rehearsal conditions."} {"id": "PMID:1272678", "title": "Integration of post-exposural directional scanning and cerebral dominance explanations of lateral differences in trachistoscopic recognition.", "content": "Post-exposural directional scanning and cerebral dominance are major postualtes which account for lateral differences in tachistoscopic perception. These ideas can be intergrated when tachistoscopic perception is viewed as a short-term memory task. Briefly exposed stimuli not only have to be scanned, but also rehearsed, subvocally, before they can be encoded. Since most Ss are left-hemisphere dominant for language, scanned information arriving in the right hemisphere has to be sent to the left hemisphere for rehearsal. This transmission effects a loss of scanned information because it is held in a rapidly dissipating storage. These ideas account for lateral differences found with vertically and horizontally oriented targets, but methodological considerations are discussed which indicate that these notions are more clearly demonstrable with the former than latter displays .", "contents": "Integration of post-exposural directional scanning and cerebral dominance explanations of lateral differences in trachistoscopic recognition. Post-exposural directional scanning and cerebral dominance are major postualtes which account for lateral differences in tachistoscopic perception. These ideas can be intergrated when tachistoscopic perception is viewed as a short-term memory task. Briefly exposed stimuli not only have to be scanned, but also rehearsed, subvocally, before they can be encoded. Since most Ss are left-hemisphere dominant for language, scanned information arriving in the right hemisphere has to be sent to the left hemisphere for rehearsal. This transmission effects a loss of scanned information because it is held in a rapidly dissipating storage. These ideas account for lateral differences found with vertically and horizontally oriented targets, but methodological considerations are discussed which indicate that these notions are more clearly demonstrable with the former than latter displays ."} {"id": "PMID:1272679", "title": "Psychological dynamics and self-perceptions of persons with essential hypertension.", "content": "Recent literature suggests specific dynamic commonalities among hypertensives are unlikely; study of development, building and evaluation of programs tailored to the individual is in order.", "contents": "Psychological dynamics and self-perceptions of persons with essential hypertension. Recent literature suggests specific dynamic commonalities among hypertensives are unlikely; study of development, building and evaluation of programs tailored to the individual is in order."} {"id": "PMID:1272680", "title": "Use of perceptually based apparatus to train adult women's performance on a Piagetian measure of the horizontality concept.", "content": "A segmented container called the V-box was designed to train adult subjects who fail a Piagetian type measure of the horizontality concept. The first segment appears round when viewed from straight an and virtually all adults were able to predict correctly howthe water line would appear when this segment was half filled with water. Partitions can be removed and the water allowed to fill up the entire container which has straight-line boundaries. On a pretest, 28 of 43 subjects failedto indicate the water line correctly on the container, when its straight-line characteristics were apparent. Of these 28, 18 were able to do so after being exposed gradually to the container's rounded segment and, step by step, to its elongated segments with straight-line boundaries. The difference in pre- to posttest change in performance between these 18 subjects and the 10 control subjects was significant.", "contents": "Use of perceptually based apparatus to train adult women's performance on a Piagetian measure of the horizontality concept. A segmented container called the V-box was designed to train adult subjects who fail a Piagetian type measure of the horizontality concept. The first segment appears round when viewed from straight an and virtually all adults were able to predict correctly howthe water line would appear when this segment was half filled with water. Partitions can be removed and the water allowed to fill up the entire container which has straight-line boundaries. On a pretest, 28 of 43 subjects failedto indicate the water line correctly on the container, when its straight-line characteristics were apparent. Of these 28, 18 were able to do so after being exposed gradually to the container's rounded segment and, step by step, to its elongated segments with straight-line boundaries. The difference in pre- to posttest change in performance between these 18 subjects and the 10 control subjects was significant."} {"id": "PMID:1272682", "title": "Hypnotic suggestion of stimulus change and visual cortical evoked potential.", "content": "Two experiments were conducted to determine whether the hypnotic suggestion of stimulus intensity change would affect the physical parameters (latencies, amplitudes) of the visual cortical evoked potential. Stimulus intensity was kept constant as visual cortical evoked potentials were measured under conditions in which it was suggested that stimuli were \"bright\" or \"dim\". The results of both experiments led to the conclusion that, under the present condition, hypnotic suggestion of stimulus intensity change did not result in changes in visual cortical evoked potentials.", "contents": "Hypnotic suggestion of stimulus change and visual cortical evoked potential. Two experiments were conducted to determine whether the hypnotic suggestion of stimulus intensity change would affect the physical parameters (latencies, amplitudes) of the visual cortical evoked potential. Stimulus intensity was kept constant as visual cortical evoked potentials were measured under conditions in which it was suggested that stimuli were \"bright\" or \"dim\". The results of both experiments led to the conclusion that, under the present condition, hypnotic suggestion of stimulus intensity change did not result in changes in visual cortical evoked potentials."} {"id": "PMID:1272683", "title": "Comparison of nonretarded and mentally retarded children on tasks involving direct and rule-governed imitation.", "content": "The influence of intellectual level and social reinforcement on imitation learning was examined. Tasks involving direct and rule-governed imitation of a mode were presented to 20 mentally retarded and 20 nonretarded children. The children within each group were randomly assigned to either an affective (\"good-fine\") or an informative (\"correct-right\") social reinforcement condition. Reinforcement, administered on a fixed ration (FR4) schedule, was contingent on the child's imitative behavior. A multivariate analysis of variance showed that both the Population X Reinforcement Type interaction and the Reinforcement main effect were significant. Univariate follow-up tests showed that only rule-governed imitation contributed significantly to the multivariate effects. Analysis of simple effects indicated that retarded children performed optimally under affective reinforcement, while the nonretarded children performed highest under informative reinforcement.", "contents": "Comparison of nonretarded and mentally retarded children on tasks involving direct and rule-governed imitation. The influence of intellectual level and social reinforcement on imitation learning was examined. Tasks involving direct and rule-governed imitation of a mode were presented to 20 mentally retarded and 20 nonretarded children. The children within each group were randomly assigned to either an affective (\"good-fine\") or an informative (\"correct-right\") social reinforcement condition. Reinforcement, administered on a fixed ration (FR4) schedule, was contingent on the child's imitative behavior. A multivariate analysis of variance showed that both the Population X Reinforcement Type interaction and the Reinforcement main effect were significant. Univariate follow-up tests showed that only rule-governed imitation contributed significantly to the multivariate effects. Analysis of simple effects indicated that retarded children performed optimally under affective reinforcement, while the nonretarded children performed highest under informative reinforcement."} {"id": "PMID:1272684", "title": "Learning disabilities and central nervous system involvement.", "content": "The relation of damage to the central nervous system to learning disabilities remains a continuing issue. This study explored how learning disable children fare on the Visual Retention Test. Analysis of correct scores and errors for the 24 children responding to Administration A would ordinarily suggest a primary relationship (t = 2.60, p less than .02; t = 4.01, p less than .001, respectively). However, since extensive medical and case history material yielded no evidence of cerebral injury or disease and since the impact of short-term memory (Administration D) led to no further performance decrement (t less than 1.00), additional research must determine a more precise understanding of perceptual dysfunction and the role of short-term memory in regard to learning disabilities.", "contents": "Learning disabilities and central nervous system involvement. The relation of damage to the central nervous system to learning disabilities remains a continuing issue. This study explored how learning disable children fare on the Visual Retention Test. Analysis of correct scores and errors for the 24 children responding to Administration A would ordinarily suggest a primary relationship (t = 2.60, p less than .02; t = 4.01, p less than .001, respectively). However, since extensive medical and case history material yielded no evidence of cerebral injury or disease and since the impact of short-term memory (Administration D) led to no further performance decrement (t less than 1.00), additional research must determine a more precise understanding of perceptual dysfunction and the role of short-term memory in regard to learning disabilities."} {"id": "PMID:1272685", "title": "Comparison of schizophrenics and normals on a visual search task.", "content": "The response times of 16 paranoids, 16 nonparanoids and 16 normals were compared on a search task which required subjects to identify target letters embedded in displays of varying numbers of non-targets. The rate on increase in response times with increased numbers of letters displayed was not markedly different for the various groups, although a derived measure of decision and response-selection time indicated that normals selected responses more rapidly. When compared with normals, schizophrenics seemed to experience more difficulty in response selection and decision than in processing visual stimulus information.", "contents": "Comparison of schizophrenics and normals on a visual search task. The response times of 16 paranoids, 16 nonparanoids and 16 normals were compared on a search task which required subjects to identify target letters embedded in displays of varying numbers of non-targets. The rate on increase in response times with increased numbers of letters displayed was not markedly different for the various groups, although a derived measure of decision and response-selection time indicated that normals selected responses more rapidly. When compared with normals, schizophrenics seemed to experience more difficulty in response selection and decision than in processing visual stimulus information."} {"id": "PMID:1272686", "title": "Effects of set, setting, and sedatives, on reaction time.", "content": "The effects of sessions, individual characteristics, group behavior, sedative medications, and pharmacological anticipation, on simple visual and auditory reaction time were evaluated with a randomized block design. The project involved 4 separate small groups of 5 to 9 healthy young adults who met 4 times for 9 hr. over 4 mo. and received 4 drug regimens under controlled conditions. Attitudes toward the experiment, which were mainly related to an early fear of potent drugs and late feelings of weariness, markedly affected reaction time. This effect decreased the test-retest reliability of the instrument, hence its sensitivity. Group behavior, subjective feelings attributable to the medications, and pharmacological anticipation, on the other hand, did not seem to have affected psychomotor performance. The effects of sedatives were much more marked and consistent with reaction time than with subjective responses, which primarily represented the influence of anticipation. This dissociation between objective and subjective behavior indicates that the subjects acted according to the drugs which they had taken but felt according to what they believed they had received.", "contents": "Effects of set, setting, and sedatives, on reaction time. The effects of sessions, individual characteristics, group behavior, sedative medications, and pharmacological anticipation, on simple visual and auditory reaction time were evaluated with a randomized block design. The project involved 4 separate small groups of 5 to 9 healthy young adults who met 4 times for 9 hr. over 4 mo. and received 4 drug regimens under controlled conditions. Attitudes toward the experiment, which were mainly related to an early fear of potent drugs and late feelings of weariness, markedly affected reaction time. This effect decreased the test-retest reliability of the instrument, hence its sensitivity. Group behavior, subjective feelings attributable to the medications, and pharmacological anticipation, on the other hand, did not seem to have affected psychomotor performance. The effects of sedatives were much more marked and consistent with reaction time than with subjective responses, which primarily represented the influence of anticipation. This dissociation between objective and subjective behavior indicates that the subjects acted according to the drugs which they had taken but felt according to what they believed they had received."} {"id": "PMID:1272687", "title": "Note on selective effects of short-term tobacco-abstinence on complex versus simple mental tasks.", "content": "Effects of a 15-hr. abstention from tobacco smoking in 12 habitual smokers were examined with 3 complex cognitive tests and 2 simple perceptual tests. Abstaining from tobacco led to improved performance on the complex tests but no change on the simple ones. The results are interpreted in terms of the inverted-U relation between performance and arousal.", "contents": "Note on selective effects of short-term tobacco-abstinence on complex versus simple mental tasks. Effects of a 15-hr. abstention from tobacco smoking in 12 habitual smokers were examined with 3 complex cognitive tests and 2 simple perceptual tests. Abstaining from tobacco led to improved performance on the complex tests but no change on the simple ones. The results are interpreted in terms of the inverted-U relation between performance and arousal."} {"id": "PMID:1272688", "title": "Mutual visual regard during mother-infant play.", "content": "Mutual visual regard was observed in 48 mother-infant dyads during a 6-min. play session. Infant-mother dyads containing 4 mo. -olds displayed significantly more mutual visual regard than dyads containing 6- or 8-mo.-olds. In addition, the more time infants spent in face-to-face interaction with mother, the more smiling they engaged in. No sex difference were observed.", "contents": "Mutual visual regard during mother-infant play. Mutual visual regard was observed in 48 mother-infant dyads during a 6-min. play session. Infant-mother dyads containing 4 mo. -olds displayed significantly more mutual visual regard than dyads containing 6- or 8-mo.-olds. In addition, the more time infants spent in face-to-face interaction with mother, the more smiling they engaged in. No sex difference were observed."} {"id": "PMID:1272689", "title": "Cognitive style and the Perky effect.", "content": "Depending on inner versus outer frames of reference in Witkin's sense parallels a subject's tendency to distinguish between internal images and external percepts. A rank-order correlation of .69 (N = 22) was found between scores on a task designed to test the latter tendency and scores on the rod-and-frame task.", "contents": "Cognitive style and the Perky effect. Depending on inner versus outer frames of reference in Witkin's sense parallels a subject's tendency to distinguish between internal images and external percepts. A rank-order correlation of .69 (N = 22) was found between scores on a task designed to test the latter tendency and scores on the rod-and-frame task."} {"id": "PMID:1272690", "title": "Koppitz errors on the Bender-Gestalt for adult retardates: normative data.", "content": "Normative data on the Koppitz developmental scoring system for the Bender-Gestalt test were derived from a sample which included 510 protocols of adult resident retardates. Percentile norms are presented on Koppitz error scores for three AAMD ranges of retardation based on WAIS IQs and two AAMD ranges of retardation based on Stanford-Binet IQs.", "contents": "Koppitz errors on the Bender-Gestalt for adult retardates: normative data. Normative data on the Koppitz developmental scoring system for the Bender-Gestalt test were derived from a sample which included 510 protocols of adult resident retardates. Percentile norms are presented on Koppitz error scores for three AAMD ranges of retardation based on WAIS IQs and two AAMD ranges of retardation based on Stanford-Binet IQs."} {"id": "PMID:1272691", "title": "Convergent and discriminant relationships between factor matrices of motor performance and arousal data.", "content": "An experimental study was conducted to demonstrate the value of a procedure for analyzing motor performance data. A sample of 156 subjects practiced on two instruments for motor learning while arousal data were recorded. Each set of data was submitted to an analysis of principal components and four components resulted for each set of data. Similarity coefficients were calculated for pairs of component matrices after rotation to maximum similarity. The similarity coefficients exhibit a consistent pattern which provides meaningful information concerning influence of experimental conditions on performance data.", "contents": "Convergent and discriminant relationships between factor matrices of motor performance and arousal data. An experimental study was conducted to demonstrate the value of a procedure for analyzing motor performance data. A sample of 156 subjects practiced on two instruments for motor learning while arousal data were recorded. Each set of data was submitted to an analysis of principal components and four components resulted for each set of data. Similarity coefficients were calculated for pairs of component matrices after rotation to maximum similarity. The similarity coefficients exhibit a consistent pattern which provides meaningful information concerning influence of experimental conditions on performance data."} {"id": "PMID:1272693", "title": "Personality traits and their relationship to traffic violations.", "content": "There is a relationship between personality traits of enlisted personnel at one mid-west Air Force Base and their frequency of moving violations. The 52 individuals who received one or two moving violations were more emotionally stable than the 33 non-offenders and the 18 chronic offenders. Discriminant analysis showed significant differences between the personality characteristics of the occasional offender and the other two groups, but none between the chronic offender and the non-offender. The personality characteristics of the chronic offender resembled those of Zelhart's alcoholic offender and Dunbar's \"accident-prone\" individual. Additional research using a more heterogeneous sample might make possible identification of the high-frequency traffic violator by means of personality characteristics measured after his first offense.", "contents": "Personality traits and their relationship to traffic violations. There is a relationship between personality traits of enlisted personnel at one mid-west Air Force Base and their frequency of moving violations. The 52 individuals who received one or two moving violations were more emotionally stable than the 33 non-offenders and the 18 chronic offenders. Discriminant analysis showed significant differences between the personality characteristics of the occasional offender and the other two groups, but none between the chronic offender and the non-offender. The personality characteristics of the chronic offender resembled those of Zelhart's alcoholic offender and Dunbar's \"accident-prone\" individual. Additional research using a more heterogeneous sample might make possible identification of the high-frequency traffic violator by means of personality characteristics measured after his first offense."} {"id": "PMID:1272694", "title": "Comparison of women's studies students with female golf star athletes on the 16 PF.", "content": "29 female students in the first author's psychology of women took the 16 PF, along with 8 female golf stars and 8 average female golf team members. The women's studies students were significantly more venture-some, more tough-minded, and more imaginative than the female golf stars.", "contents": "Comparison of women's studies students with female golf star athletes on the 16 PF. 29 female students in the first author's psychology of women took the 16 PF, along with 8 female golf stars and 8 average female golf team members. The women's studies students were significantly more venture-some, more tough-minded, and more imaginative than the female golf stars."} {"id": "PMID:1272695", "title": "Competitive behavior and perceived aggression.", "content": "In groups of 39 males and 39 female undergraduates played a reaction-time game in which descriptions of a player's shock settings were constant or consistently below or above another player's; wins were varied. Ratings of aggression, offensiveness, positivity on semantic scales showed naive subjects considered the offensive or defensive nature of obseved behavior in making ratings.", "contents": "Competitive behavior and perceived aggression. In groups of 39 males and 39 female undergraduates played a reaction-time game in which descriptions of a player's shock settings were constant or consistently below or above another player's; wins were varied. Ratings of aggression, offensiveness, positivity on semantic scales showed naive subjects considered the offensive or defensive nature of obseved behavior in making ratings."} {"id": "PMID:1272696", "title": "Potential artifact in dichoptic backward masking.", "content": "Under some conditions a dark interval in the target eye may be concomitant with presentation of a dichoptic mask. Results show that this monoptic dark interval contributes to the over-all observed dichoptic masking effect.", "contents": "Potential artifact in dichoptic backward masking. Under some conditions a dark interval in the target eye may be concomitant with presentation of a dichoptic mask. Results show that this monoptic dark interval contributes to the over-all observed dichoptic masking effect."} {"id": "PMID:1272697", "title": "Causal attribution of success and failure as a function or authoritarianism and sex.", "content": "We predicted that authoritarian actors would engage in defensive attribution, and authoritarian observers would derogate the other, to a greater extent than egalitarian perceivers. 48 male and 48 female college students were run in pairs of same sex and authoritarianism. A set of easy anagrams was given to subjects in success conditions and difficult anagrams to those in failure conditions. Each subject rated own outcome and other outcome in terms of internal factors of ability and effort, and external factors of task and luck. We found that authoritarian actors were more internal than egalitarian actors only in the condition own success-other's failure. Authoritarian observers, as compared to egalitarians, were more external for other's success and more internal for other's failure only when own outcome was successful. It seems that authoritarian perceivers exaggerate their abilities and derogate the other only when they are clearly in a superior position vis-a-vis the other. There were no sex differences as a function of outcome and authoritarianism.", "contents": "Causal attribution of success and failure as a function or authoritarianism and sex. We predicted that authoritarian actors would engage in defensive attribution, and authoritarian observers would derogate the other, to a greater extent than egalitarian perceivers. 48 male and 48 female college students were run in pairs of same sex and authoritarianism. A set of easy anagrams was given to subjects in success conditions and difficult anagrams to those in failure conditions. Each subject rated own outcome and other outcome in terms of internal factors of ability and effort, and external factors of task and luck. We found that authoritarian actors were more internal than egalitarian actors only in the condition own success-other's failure. Authoritarian observers, as compared to egalitarians, were more external for other's success and more internal for other's failure only when own outcome was successful. It seems that authoritarian perceivers exaggerate their abilities and derogate the other only when they are clearly in a superior position vis-a-vis the other. There were no sex differences as a function of outcome and authoritarianism."} {"id": "PMID:1272699", "title": "Recall of letters from the left and right visual half-fields under unilater and bilateral presentation.", "content": "Bilateral presentation in the visual half-field greatly increases superiority of the right visual half-field in tachistoscopic recognition of words when fixation is controlled using a center digit. Two experiments explored left-right asymmetry with bilateral presentation on a visual half-field short-term memory task, with fixation controlled by a sequence of letters at fixation. A total of 40 subjects served in the two experiments, which compared recall under unilateral versus bilateral presentation to the visual half-field. Bilateral presentation increased over-all recall from the last serial position but did not alter asymmetry of the visual half-field. As in previous experiments, the superiority of the right visual half-field was greatest from the initial serial positions. It was concluded that asymmetry of the visual half-field on this recall task with controlled fixation depends primarily on masking and short-term memory but is independent of unilateral-bilateral presentation.", "contents": "Recall of letters from the left and right visual half-fields under unilater and bilateral presentation. Bilateral presentation in the visual half-field greatly increases superiority of the right visual half-field in tachistoscopic recognition of words when fixation is controlled using a center digit. Two experiments explored left-right asymmetry with bilateral presentation on a visual half-field short-term memory task, with fixation controlled by a sequence of letters at fixation. A total of 40 subjects served in the two experiments, which compared recall under unilateral versus bilateral presentation to the visual half-field. Bilateral presentation increased over-all recall from the last serial position but did not alter asymmetry of the visual half-field. As in previous experiments, the superiority of the right visual half-field was greatest from the initial serial positions. It was concluded that asymmetry of the visual half-field on this recall task with controlled fixation depends primarily on masking and short-term memory but is independent of unilateral-bilateral presentation."} {"id": "PMID:1272700", "title": "Orienting responses as a function of age and task complexity.", "content": "Aged-related differences in the elicitation and habituation of orienting responses to the onset and offset of stimuli have been suggested by several authors. Electrodermal and cardiac orienting responses to the onset and offset of a visual stimulus were measured in three age groups (4 yr., 7 yr., and undergraduate). Each S made one of three judgments: non-signal (observe stimulus), content (color of stimulus), and duration (length of time stimulus presented). Few age differences were found in elicitation or habituation of orienting responses to stimulus onset or offset. There was a trend for elicitation of orienting responses to stimulus offset to be age-related, but the failure to find any other age-related changes made this difference somewhat questionable. Instructions as to the judgement to be made by S were the primary determinants of orienting responses to stimulus onset and offset across all age groups.", "contents": "Orienting responses as a function of age and task complexity. Aged-related differences in the elicitation and habituation of orienting responses to the onset and offset of stimuli have been suggested by several authors. Electrodermal and cardiac orienting responses to the onset and offset of a visual stimulus were measured in three age groups (4 yr., 7 yr., and undergraduate). Each S made one of three judgments: non-signal (observe stimulus), content (color of stimulus), and duration (length of time stimulus presented). Few age differences were found in elicitation or habituation of orienting responses to stimulus onset or offset. There was a trend for elicitation of orienting responses to stimulus offset to be age-related, but the failure to find any other age-related changes made this difference somewhat questionable. Instructions as to the judgement to be made by S were the primary determinants of orienting responses to stimulus onset and offset across all age groups."} {"id": "PMID:1272703", "title": "Detection of a deficit in visual discrimination of pattern following lesions of anterior cortex: role of type of motivation.", "content": "6 albino rats were trained under appetitive motivation to perform diametrically opposed visual discriminations of pattern via opposite eyes. Small lesions were subsequently placed unilaterally in anterior neocortex. Following a period of post-surgical recovery, subjects were re-trained on the diammetrically opposed discriminations in alternating 10-trial blocks. Every subject made more post-surgical errors on the discrimination mediated by the eye contralateral to the lesion. Since albino rats have virtually complete decussation of the visual system, this indicates selective impairment in mediation of performance of pattern discrimination in the part of the lesioned hemispheres. Thus, findings previously obtained in studies involving aversive motivation are general to appetitively motivated tasks.", "contents": "Detection of a deficit in visual discrimination of pattern following lesions of anterior cortex: role of type of motivation. 6 albino rats were trained under appetitive motivation to perform diametrically opposed visual discriminations of pattern via opposite eyes. Small lesions were subsequently placed unilaterally in anterior neocortex. Following a period of post-surgical recovery, subjects were re-trained on the diammetrically opposed discriminations in alternating 10-trial blocks. Every subject made more post-surgical errors on the discrimination mediated by the eye contralateral to the lesion. Since albino rats have virtually complete decussation of the visual system, this indicates selective impairment in mediation of performance of pattern discrimination in the part of the lesioned hemispheres. Thus, findings previously obtained in studies involving aversive motivation are general to appetitively motivated tasks."} {"id": "PMID:1272704", "title": "The unimportance of experimenter-bias in sensory deprivation research.", "content": "3 graduate student experimenters' expectations about the stress reaction of 24 subjects to sensory deprivation or to an ambulatory control condition were factorially manipulated. No significant differences were found for experimenters' expectation, directly or through interaction. Results were interpreted as a refutation ofthe assumed pervasiveness of experimenter-bias effects.", "contents": "The unimportance of experimenter-bias in sensory deprivation research. 3 graduate student experimenters' expectations about the stress reaction of 24 subjects to sensory deprivation or to an ambulatory control condition were factorially manipulated. No significant differences were found for experimenters' expectation, directly or through interaction. Results were interpreted as a refutation ofthe assumed pervasiveness of experimenter-bias effects."} {"id": "PMID:1272705", "title": "Time delay in estimation of angles.", "content": "The hypotheses were that a 2-min. delay as opposed to a 2-sec. delay between observation and mechanical estimation to an acute angle will increase the likelihood of overestimation of that angle and that minimal-surround cue-conditions would produce greater overestimation than maximal cue-conditions. 40 subjects estimated a 54 degrees acute angle presented behind a 2-way mirror in one of the four treatment combinations in a 2 X 2 factorial design. A 2-min. time delay caused significantly larger estimates of the angle. Overestimation in the maximal cue-condition was significant but the underestimate in the minimal cue-conditions was not. Cue-conditions were not significantly different from one another.", "contents": "Time delay in estimation of angles. The hypotheses were that a 2-min. delay as opposed to a 2-sec. delay between observation and mechanical estimation to an acute angle will increase the likelihood of overestimation of that angle and that minimal-surround cue-conditions would produce greater overestimation than maximal cue-conditions. 40 subjects estimated a 54 degrees acute angle presented behind a 2-way mirror in one of the four treatment combinations in a 2 X 2 factorial design. A 2-min. time delay caused significantly larger estimates of the angle. Overestimation in the maximal cue-condition was significant but the underestimate in the minimal cue-conditions was not. Cue-conditions were not significantly different from one another."} {"id": "PMID:1272707", "title": "Autokinetic movement in geometric illusions: a note.", "content": "Four static geometrical illusions were presented in an autokinetic movement situation. 50 Ss saw each form four times. Of the total responses, 36% were no-movement responses while 37% of the time the total figure was seen as moving. The meaning 27% of the responses involved apparent movement in only a part of the figure. In general, the elements seen as moving are the parts misperceived in the static geometrical illusion.", "contents": "Autokinetic movement in geometric illusions: a note. Four static geometrical illusions were presented in an autokinetic movement situation. 50 Ss saw each form four times. Of the total responses, 36% were no-movement responses while 37% of the time the total figure was seen as moving. The meaning 27% of the responses involved apparent movement in only a part of the figure. In general, the elements seen as moving are the parts misperceived in the static geometrical illusion."} {"id": "PMID:1272708", "title": "Hand movements which cross the body midline: findings relating age differences to handedness.", "content": "Performance of 200 children (5 groups, 4 to 12 yr.) in an experimental study of spatial development was analyzed in terms of hand preference and differences in laterality of response. In accord with the literature a cross-lateral inhibition effect was confirmed but there were marked differences between hands. The supposed 'body midline' seemed to offer more resistance to one hand than to the other. Alternative explanations are suggested.", "contents": "Hand movements which cross the body midline: findings relating age differences to handedness. Performance of 200 children (5 groups, 4 to 12 yr.) in an experimental study of spatial development was analyzed in terms of hand preference and differences in laterality of response. In accord with the literature a cross-lateral inhibition effect was confirmed but there were marked differences between hands. The supposed 'body midline' seemed to offer more resistance to one hand than to the other. Alternative explanations are suggested."} {"id": "PMID:1272710", "title": "Signal pulse-rate and judged duration.", "content": "Therories which construct perception of time from content of input predict monotonic functions of rate-judged duration of stimuli, and do not account for intersensory differences. Two experiments required Ss to compare directly the durations of paird lights or sounds pulsed at various rates to produce discriminable beats and flickers (6.0, 10.0, 14.0 Hz), and steady signals. Pulsed lights, not sounds, were judged longer than steady, and this visual effect was identical for all flicker rates. Faster pulsled sounds and lights were judged longer than slower ones for all frequency combinations except for 10.0 to 14.0-Hz comparisons with vision. No monotonic function of ratejudged durations of pulses was obtained; the effect was all-or-none. Although pulse rate did affect judged duration, neither simple functions nor symmetry across senses was found.", "contents": "Signal pulse-rate and judged duration. Therories which construct perception of time from content of input predict monotonic functions of rate-judged duration of stimuli, and do not account for intersensory differences. Two experiments required Ss to compare directly the durations of paird lights or sounds pulsed at various rates to produce discriminable beats and flickers (6.0, 10.0, 14.0 Hz), and steady signals. Pulsed lights, not sounds, were judged longer than steady, and this visual effect was identical for all flicker rates. Faster pulsled sounds and lights were judged longer than slower ones for all frequency combinations except for 10.0 to 14.0-Hz comparisons with vision. No monotonic function of ratejudged durations of pulses was obtained; the effect was all-or-none. Although pulse rate did affect judged duration, neither simple functions nor symmetry across senses was found."} {"id": "PMID:1272712", "title": "Amnesia for random shapes following unilateral and bilateral electronvulsive shock therapy.", "content": "Three 16-point shapes were shown to 15 patients before undergoing either unilateral or bilateral electroconvulsive therapy. They were then tested for recognition following therapy. The same subjects were similarly tested for recognition memory with no intervening shock. Analysis of variance indicated no significant differential effects of the two methods of electroshock application.", "contents": "Amnesia for random shapes following unilateral and bilateral electronvulsive shock therapy. Three 16-point shapes were shown to 15 patients before undergoing either unilateral or bilateral electroconvulsive therapy. They were then tested for recognition following therapy. The same subjects were similarly tested for recognition memory with no intervening shock. Analysis of variance indicated no significant differential effects of the two methods of electroshock application."} {"id": "PMID:1272713", "title": "Numerosity discrimination of tactile stimuli.", "content": "The ability of 40 college students to discriminate the number of tactile stimuli presented simultaneously was measured in two experiments. Simulation was provided by 12 solenoids fixed to points on the arms and legs. Exp. I showed a mean correct discrimination level of between 1.55 and 2.10 solenoids. Exp II compared discrimination of numerosity by a group who received immediate feedback with a no-feedback control group. Feedback produced a small increase in this ability. However, the most stimulation points correctly discriminated did not exceed three. The data are discussed in terms of the possible role of cutaneous masking.", "contents": "Numerosity discrimination of tactile stimuli. The ability of 40 college students to discriminate the number of tactile stimuli presented simultaneously was measured in two experiments. Simulation was provided by 12 solenoids fixed to points on the arms and legs. Exp. I showed a mean correct discrimination level of between 1.55 and 2.10 solenoids. Exp II compared discrimination of numerosity by a group who received immediate feedback with a no-feedback control group. Feedback produced a small increase in this ability. However, the most stimulation points correctly discriminated did not exceed three. The data are discussed in terms of the possible role of cutaneous masking."} {"id": "PMID:1272714", "title": "Selective attention in children with learning disabilities.", "content": "49 children, aged 11 to 14 yr., a learning disabled group and a normal group, performed a primary, reading-like, card-sorting task. After they completed the primary task, they were tested for memory of incidental materials presented during learning. While the normal children showed better recall of incidental materials related to the primary task, 24 children with disabilities showed superior recall of material irrelevant to the primary task. The results were discussed in terms of alternative \"motivational\" and \"developmental lag\" interpretations.", "contents": "Selective attention in children with learning disabilities. 49 children, aged 11 to 14 yr., a learning disabled group and a normal group, performed a primary, reading-like, card-sorting task. After they completed the primary task, they were tested for memory of incidental materials presented during learning. While the normal children showed better recall of incidental materials related to the primary task, 24 children with disabilities showed superior recall of material irrelevant to the primary task. The results were discussed in terms of alternative \"motivational\" and \"developmental lag\" interpretations."} {"id": "PMID:1272715", "title": "Development of ability to perceive and produce pictorial depth cue of overlapping.", "content": "The perception of the pictorial depth cue of overlapping was studied in children 3, 5, and 7 yr. old. Both a sequential and a simultaneous picture/object-matching task were used to test sensitivity. All age groups successfully perceived the depth relation information provided by pictorial overlapping. Height on the picture plane, which projectively covaries with overlapping, was not consistently used as a depth cue by any age group. Children's drawings were also analyzed for the presence of distance information. The drawings of the 3- and 5-yr. old children contained no overlapping cues and indicated a general lack of understanding of the third demension behind the picture plane. Seven-yr.-old children showed the beginnings of this understanding through their use of size perspective and height on the picture plane as depth cues. For all ages the production of the overlapping cue lags behind its perception.", "contents": "Development of ability to perceive and produce pictorial depth cue of overlapping. The perception of the pictorial depth cue of overlapping was studied in children 3, 5, and 7 yr. old. Both a sequential and a simultaneous picture/object-matching task were used to test sensitivity. All age groups successfully perceived the depth relation information provided by pictorial overlapping. Height on the picture plane, which projectively covaries with overlapping, was not consistently used as a depth cue by any age group. Children's drawings were also analyzed for the presence of distance information. The drawings of the 3- and 5-yr. old children contained no overlapping cues and indicated a general lack of understanding of the third demension behind the picture plane. Seven-yr.-old children showed the beginnings of this understanding through their use of size perspective and height on the picture plane as depth cues. For all ages the production of the overlapping cue lags behind its perception."} {"id": "PMID:1272716", "title": "Selected Designs and the background interference procedure: evaluation of use with a specific population.", "content": "A combination of Selected Designs and Background Interference Procedure was administered to 31 (11 men, 20 women) adult inpatients. Only 48% of the protocols showed discriminable differences between the first and second reproductions.", "contents": "Selected Designs and the background interference procedure: evaluation of use with a specific population. A combination of Selected Designs and Background Interference Procedure was administered to 31 (11 men, 20 women) adult inpatients. Only 48% of the protocols showed discriminable differences between the first and second reproductions."} {"id": "PMID:1272718", "title": "Electromyographic responses in infants after auditory stimulation.", "content": "49 of 50 newborn infants, when presented with a strong auditory stimulus, showed significant increases in EMG potential. The infant who failed initially responded when rechecked in 1 mo. The results suggest it may be possible to develop an EMG-Audiometric process which could be employed in screening hearing of newborn infants.", "contents": "Electromyographic responses in infants after auditory stimulation. 49 of 50 newborn infants, when presented with a strong auditory stimulus, showed significant increases in EMG potential. The infant who failed initially responded when rechecked in 1 mo. The results suggest it may be possible to develop an EMG-Audiometric process which could be employed in screening hearing of newborn infants."} {"id": "PMID:1272719", "title": "Eye dominance in a reading clinic population.", "content": "Eye dominance tests (24 comparisons) varied markedly in aggreement with each other for 225 consecutive screening evaluation (5 yr. to 55 yr.) in a reading clinic.", "contents": "Eye dominance in a reading clinic population. Eye dominance tests (24 comparisons) varied markedly in aggreement with each other for 225 consecutive screening evaluation (5 yr. to 55 yr.) in a reading clinic."} {"id": "PMID:1272720", "title": "Autokinetic movement as a function of symbolic meaning of target shape.", "content": "The autokinetic movement responses of 10 American, 10 Chinese, and 10 Iranian students to religious symbols and control stimuli were measured. The hypothesis of differential direction response as a function of the target shapes was supported. Iranian students did show a pattern of responding significantly different from the American and Chinese.", "contents": "Autokinetic movement as a function of symbolic meaning of target shape. The autokinetic movement responses of 10 American, 10 Chinese, and 10 Iranian students to religious symbols and control stimuli were measured. The hypothesis of differential direction response as a function of the target shapes was supported. Iranian students did show a pattern of responding significantly different from the American and Chinese."} {"id": "PMID:1272721", "title": "Self-disclosure in friendship.", "content": "An experimental investigation of the influence of self-disclosure on friendship was conducted by manipulating the level of self-disclosure. 65 same-sex pairs were randomly assigned to one of three treatment conditions, intimate self-disclosure, nonintimate self-disclosure and control (no disclosure); the treatment conditions were independently verified by judges' ratings. One member of each pair was randomly selected as the confederate or first speaker and was provided with a list of 7 conversation topics. There were no lists provided in the control condition. The dependent variable, level of friendship as measured by the Acquaintance Description Form (Wright, 1969), was rated before and after Ss engaged in self-disclosure, and the influence of the experimental conditions on friendship scores was assessed by analyses of covariance. The results showed that the general level of friendship increased as a function of intimate and nonintimate self-disclosure; however, intimate disclosure produced greater increases in friendship than nonintimate disclosure. The unique influence of self-disclosure on male friendship patterns is discussed.", "contents": "Self-disclosure in friendship. An experimental investigation of the influence of self-disclosure on friendship was conducted by manipulating the level of self-disclosure. 65 same-sex pairs were randomly assigned to one of three treatment conditions, intimate self-disclosure, nonintimate self-disclosure and control (no disclosure); the treatment conditions were independently verified by judges' ratings. One member of each pair was randomly selected as the confederate or first speaker and was provided with a list of 7 conversation topics. There were no lists provided in the control condition. The dependent variable, level of friendship as measured by the Acquaintance Description Form (Wright, 1969), was rated before and after Ss engaged in self-disclosure, and the influence of the experimental conditions on friendship scores was assessed by analyses of covariance. The results showed that the general level of friendship increased as a function of intimate and nonintimate self-disclosure; however, intimate disclosure produced greater increases in friendship than nonintimate disclosure. The unique influence of self-disclosure on male friendship patterns is discussed."} {"id": "PMID:1272722", "title": "Comparison of deaf and hearing children on body-object localization.", "content": "20 profoundly deaf and 20 normal hearing children from ages 10 to 13 were compared as to their ability to locate visually the position of apparent vertical and the apparent location of the longitudinal axis of the body under erect and 30 degrees left and right body-tilt. Both deaf and normal hearing children were able accurately to locate a rod to the apparent visual vertical, but deaf children were significantly more accurate in aligning a rod to their apparent body-position than hearing children. This finding is discussed from both a learning view and from a hypothesis of developmental lag.", "contents": "Comparison of deaf and hearing children on body-object localization. 20 profoundly deaf and 20 normal hearing children from ages 10 to 13 were compared as to their ability to locate visually the position of apparent vertical and the apparent location of the longitudinal axis of the body under erect and 30 degrees left and right body-tilt. Both deaf and normal hearing children were able accurately to locate a rod to the apparent visual vertical, but deaf children were significantly more accurate in aligning a rod to their apparent body-position than hearing children. This finding is discussed from both a learning view and from a hypothesis of developmental lag."} {"id": "PMID:1272723", "title": "Effects of prior hypoxia exposure on visual target detection during later more severe hypoxia.", "content": "Three groups of 15 subjects each were exposed to 3 different combinations of intermediate (staging) altitudes and exposure times, and were then tested for visual target detection capability at a final altitude of 4300 m. All groups with staging exposure performed better at altitude and had fewer symptoms of acute mountain sickness than a fourth group which went directly to 4300 m altitude from sea level. The data showed that task factors of both viewing distance and degree of peripheral placement of the target significantly influenced detection time within all groups regardless of variations in exposure to altitude.", "contents": "Effects of prior hypoxia exposure on visual target detection during later more severe hypoxia. Three groups of 15 subjects each were exposed to 3 different combinations of intermediate (staging) altitudes and exposure times, and were then tested for visual target detection capability at a final altitude of 4300 m. All groups with staging exposure performed better at altitude and had fewer symptoms of acute mountain sickness than a fourth group which went directly to 4300 m altitude from sea level. The data showed that task factors of both viewing distance and degree of peripheral placement of the target significantly influenced detection time within all groups regardless of variations in exposure to altitude."} {"id": "PMID:1272724", "title": "Cardiac cycle phase and movement and reaction times.", "content": "The EKG was recorded while Ss differentially responded to auditory or visual stimuli in a reaction time task. The EKG record was analyzed by dividing each R-R interval encompassing a stimulus presentation into 9 equal phases. Reaction times were determined as a function of the phase encompassing stimulus onset while movement times were determined for the phase in which the response was initiated. Only reaction time significantly varied with cardiac cycle, with reactions during the second phase being slower than later phases.", "contents": "Cardiac cycle phase and movement and reaction times. The EKG was recorded while Ss differentially responded to auditory or visual stimuli in a reaction time task. The EKG record was analyzed by dividing each R-R interval encompassing a stimulus presentation into 9 equal phases. Reaction times were determined as a function of the phase encompassing stimulus onset while movement times were determined for the phase in which the response was initiated. Only reaction time significantly varied with cardiac cycle, with reactions during the second phase being slower than later phases."} {"id": "PMID:1272725", "title": "Performance of retarded and nonretarded adolescents when processing relevant and irrelevant information.", "content": "The information-processing performance of 12 retarded and 12 nonretarded adolescents was compared. Using reaction time keys each subject classified color words, secondary color words, non-color words, non-sense syllables, and stick figures according to the color of ink in which each stimulus was presented. Reaction time of the nonretarded subjects was significantly faster than that of retarded subjects; color words and secondary color words significantly interfered with processing performance as measured by correct reaction time. The results indicate that the Stroop task interferes with response initiation rather than memory retrieval and that the locus of interference for retarded and nonretarded subjects is equivalent.", "contents": "Performance of retarded and nonretarded adolescents when processing relevant and irrelevant information. The information-processing performance of 12 retarded and 12 nonretarded adolescents was compared. Using reaction time keys each subject classified color words, secondary color words, non-color words, non-sense syllables, and stick figures according to the color of ink in which each stimulus was presented. Reaction time of the nonretarded subjects was significantly faster than that of retarded subjects; color words and secondary color words significantly interfered with processing performance as measured by correct reaction time. The results indicate that the Stroop task interferes with response initiation rather than memory retrieval and that the locus of interference for retarded and nonretarded subjects is equivalent."} {"id": "PMID:1272726", "title": "Laterality, hand preference, and human spatial ability.", "content": "6 left-handed females scored significantly below 60 right-handed females on a test of spatial visualization (p less than .005). 13 left-handed males showed a higher mean score than 33 right-handed males on the spatial test, although this difference was not statistically significant. These results are consistent with the hypothesis that the left cerebral hemisphere is of greater relative importance to spatial functioning in females than males.", "contents": "Laterality, hand preference, and human spatial ability. 6 left-handed females scored significantly below 60 right-handed females on a test of spatial visualization (p less than .005). 13 left-handed males showed a higher mean score than 33 right-handed males on the spatial test, although this difference was not statistically significant. These results are consistent with the hypothesis that the left cerebral hemisphere is of greater relative importance to spatial functioning in females than males."} {"id": "PMID:1272727", "title": "Perceptual reactance and melanic density.", "content": "Following assessment of eye color, a total of 108 college students (33 males and 75 females) estimated changes in sizes of standardized blocks while blindfolded. Subjects were classfied as perceptual augmenters, moderates or reducers as a function of their overestimation, accurate estimation, or underestimation, respectively, of the sizes of the blocks. A significant interaction of gender by perceptual reactance appeared, with augmenting males being rated the most dark-eyed and augmenting females being rated the most light-eyed. Interpretation of the findings was made in terms of attention to relevant cues.", "contents": "Perceptual reactance and melanic density. Following assessment of eye color, a total of 108 college students (33 males and 75 females) estimated changes in sizes of standardized blocks while blindfolded. Subjects were classfied as perceptual augmenters, moderates or reducers as a function of their overestimation, accurate estimation, or underestimation, respectively, of the sizes of the blocks. A significant interaction of gender by perceptual reactance appeared, with augmenting males being rated the most dark-eyed and augmenting females being rated the most light-eyed. Interpretation of the findings was made in terms of attention to relevant cues."} {"id": "PMID:1272728", "title": "Effects of framed spectacles and contact lenses on self-ratings of facial attractiveness.", "content": "15 females with glasses tended to defend against relatively low self-perceptions of attractiveness by de-emphasizing the influence of their eyes on facial beauty.", "contents": "Effects of framed spectacles and contact lenses on self-ratings of facial attractiveness. 15 females with glasses tended to defend against relatively low self-perceptions of attractiveness by de-emphasizing the influence of their eyes on facial beauty."} {"id": "PMID:1272729", "title": "Immediate proprioceptive decrement with hypnotic anesthesia: a preliminary report.", "content": "Hypnotic anesthesia induced in a subject's entire arem produced a decrement in proprioceptive abilities as assessed by the inability to locate the nose position with the forefinger of the anesthetized arm. The magnitude of the decrement was positively related to level of hypnotic susceptibility.", "contents": "Immediate proprioceptive decrement with hypnotic anesthesia: a preliminary report. Hypnotic anesthesia induced in a subject's entire arem produced a decrement in proprioceptive abilities as assessed by the inability to locate the nose position with the forefinger of the anesthetized arm. The magnitude of the decrement was positively related to level of hypnotic susceptibility."} {"id": "PMID:1272731", "title": "Effects of density of noise field and delay on information-processing of patterned inputs.", "content": "The present paper extends current research on pattern recognition to investigate the effects of density of noise field and delay (off) times. The results indicate major effects due to density of the noise field, on time and off time. Recognition initially declined as the density of the interference increased, then subsequently leveled off at higher interference levels. The effect of density of noise field on recognition was not consistent across all levels of either on time or off time. There was a wide range of processing-ability among Ss. Some subjects were capable of high levels of performance for very fast input rates. There was a high degree of consistency among Ss in the relative difficulty of the letters.", "contents": "Effects of density of noise field and delay on information-processing of patterned inputs. The present paper extends current research on pattern recognition to investigate the effects of density of noise field and delay (off) times. The results indicate major effects due to density of the noise field, on time and off time. Recognition initially declined as the density of the interference increased, then subsequently leveled off at higher interference levels. The effect of density of noise field on recognition was not consistent across all levels of either on time or off time. There was a wide range of processing-ability among Ss. Some subjects were capable of high levels of performance for very fast input rates. There was a high degree of consistency among Ss in the relative difficulty of the letters."} {"id": "PMID:1272732", "title": "Inability to wink an eye and eye dominance.", "content": "Data from 56 subjects in Grades 4 to 12 only able to wink one eye indicated that the non-winking eye was used as the dominant one in tests on monocular and binocular sighting.", "contents": "Inability to wink an eye and eye dominance. Data from 56 subjects in Grades 4 to 12 only able to wink one eye indicated that the non-winking eye was used as the dominant one in tests on monocular and binocular sighting."} {"id": "PMID:1272733", "title": "Interhemispheric EEG activity in normal and aphasic adults.", "content": "EEG recordings were obtained from 10 normal and 10 aphasic adults while they participated in behavioral tasks and a no performance condition. Interhemispheric asymmetry and average activity at 5 to 15 Hz in each hemisphere were compared between groups and among tasks. Asymmetry during behavioral tasks did not differ significantly between groups or among tasks, however, aphasic patients showed a significant decrease in average activity at 5 to 15 Hz on the behavioral tasks compared with the level for a non performance condition. Test-retest reliability was poor for asymmetry but acceptable for average activity at 5 to 15 Hz. Finally, asymmetry was significantly related with severity of aphasia.", "contents": "Interhemispheric EEG activity in normal and aphasic adults. EEG recordings were obtained from 10 normal and 10 aphasic adults while they participated in behavioral tasks and a no performance condition. Interhemispheric asymmetry and average activity at 5 to 15 Hz in each hemisphere were compared between groups and among tasks. Asymmetry during behavioral tasks did not differ significantly between groups or among tasks, however, aphasic patients showed a significant decrease in average activity at 5 to 15 Hz on the behavioral tasks compared with the level for a non performance condition. Test-retest reliability was poor for asymmetry but acceptable for average activity at 5 to 15 Hz. Finally, asymmetry was significantly related with severity of aphasia."} {"id": "PMID:1272735", "title": "Knowledge of results and counting of sequential light flashes by retarded and intellectually normal children.", "content": "12 adolescent retarded boys and 12 younger third-grade boys of equivalent mental age observed sequential flashes of light and made judgements of numerosity. Durations of successive flashes were 300, 500, 700, and 900 msec. in trains of 1 to 15 flashes. Over six daily sessions, subgroups receiving information about accuracy after each trial made fewer errors, and subgroups receiving none made more errors. The linear trend interaction of knowledge of results with IQ was significant, with performance of the nonretarded boys decreasing to the level of the retarded boys in the no-feedback condition. With feedback, the rate of decrease in error over sessions was similiar for both levels of IQ. The results indicate a substantial effect of knowledge of results in improving accuracy of counting by retarded and nonretarded children, this effect being relatively greater for the latter group.", "contents": "Knowledge of results and counting of sequential light flashes by retarded and intellectually normal children. 12 adolescent retarded boys and 12 younger third-grade boys of equivalent mental age observed sequential flashes of light and made judgements of numerosity. Durations of successive flashes were 300, 500, 700, and 900 msec. in trains of 1 to 15 flashes. Over six daily sessions, subgroups receiving information about accuracy after each trial made fewer errors, and subgroups receiving none made more errors. The linear trend interaction of knowledge of results with IQ was significant, with performance of the nonretarded boys decreasing to the level of the retarded boys in the no-feedback condition. With feedback, the rate of decrease in error over sessions was similiar for both levels of IQ. The results indicate a substantial effect of knowledge of results in improving accuracy of counting by retarded and nonretarded children, this effect being relatively greater for the latter group."} {"id": "PMID:1272736", "title": "Unilateral control of bilaterally symmetrical movement as factor in lateralization of speech.", "content": "A number of bilaterally symmetrical motor patterns, preformed in their basic topography at brainstem levels, are most efficiently guided through unilateral input. This concept is related to the lateralization of speech.", "contents": "Unilateral control of bilaterally symmetrical movement as factor in lateralization of speech. A number of bilaterally symmetrical motor patterns, preformed in their basic topography at brainstem levels, are most efficiently guided through unilateral input. This concept is related to the lateralization of speech."} {"id": "PMID:1272737", "title": "Temporal summation effects on lingual vibrotactile thresholds.", "content": "Ascending lingual vibrotactile thresholds at 250 Hz were obtained for four groups of normal-speaking adult subjects. Stimulus durations were varied for each respective group. Threshold values plotted as a function of stimulus duration indicated a temporal summation function occurring up to 200 msec. Findings are discussed in terms of underlying peripheral receptors and some implications for using summation measures as a basis for identifying oral sensory disorders.", "contents": "Temporal summation effects on lingual vibrotactile thresholds. Ascending lingual vibrotactile thresholds at 250 Hz were obtained for four groups of normal-speaking adult subjects. Stimulus durations were varied for each respective group. Threshold values plotted as a function of stimulus duration indicated a temporal summation function occurring up to 200 msec. Findings are discussed in terms of underlying peripheral receptors and some implications for using summation measures as a basis for identifying oral sensory disorders."} {"id": "PMID:1272738", "title": "Lateral eye-shift related to preschoolers use of descriptive language.", "content": "Lateral eye-shift in preschool children was related to the use of more nouns in description by 14 right-shifters, more adjectives by 19 left-shifters. Results suggest that differences in hemispheric activity may lead to differential language use.", "contents": "Lateral eye-shift related to preschoolers use of descriptive language. Lateral eye-shift in preschool children was related to the use of more nouns in description by 14 right-shifters, more adjectives by 19 left-shifters. Results suggest that differences in hemispheric activity may lead to differential language use."} {"id": "PMID:1272739", "title": "Primacy effect in orienting responses to auditory stimuli of tones and music.", "content": "This 25 factorial experiment investigated the primacy effect in the orienting response. The type of stimuli (tone or \"music\"), stimulus intensities (loud or soft), length of adaptation period (same, 5 or 30 sec; or different, 5 min.), interstimulus intervals (5 or 30 sec.), and sex were studied. College students, 32 males and 32 females were randomly assigned to each group. In the same condition, the tone (or music) was soft (or loud) for 5 sec. (or 30 sec.) in adaptation and was then changed alternately without interruption to loud, soft, etc. (or soft, loud, etc.) for 5 sec. (or 30 sec.). The different condition was identical except for the length of adaptation period in which the stimuli sounded continously for 5 min. Analyses of the GSR manifestation of the orienting responses indicated: (a) an over-all primacy effect with the auditory stimuli and (b) the primacy effect occurred in the 5-sec.-same but not in the 30-sec.-same condition as predicted.", "contents": "Primacy effect in orienting responses to auditory stimuli of tones and music. This 25 factorial experiment investigated the primacy effect in the orienting response. The type of stimuli (tone or \"music\"), stimulus intensities (loud or soft), length of adaptation period (same, 5 or 30 sec; or different, 5 min.), interstimulus intervals (5 or 30 sec.), and sex were studied. College students, 32 males and 32 females were randomly assigned to each group. In the same condition, the tone (or music) was soft (or loud) for 5 sec. (or 30 sec.) in adaptation and was then changed alternately without interruption to loud, soft, etc. (or soft, loud, etc.) for 5 sec. (or 30 sec.). The different condition was identical except for the length of adaptation period in which the stimuli sounded continously for 5 min. Analyses of the GSR manifestation of the orienting responses indicated: (a) an over-all primacy effect with the auditory stimuli and (b) the primacy effect occurred in the 5-sec.-same but not in the 30-sec.-same condition as predicted."} {"id": "PMID:1272740", "title": "IES Arrow-Dot longitudinal comparisons of personality development in preschool children.", "content": "19 preschool children were administered the IES Arrow-Dot test at the beginning and end of the school year and results compared with those based on a similar sample gathered the previous year. Trends for declining Impulsivity and Superego development were corroborated. Baselines for Impulsivity and Superego showed variation. Baselines and trends of rising Ego scores were supported. Results suggested suport for developmental trends of personality integration in preschool children.", "contents": "IES Arrow-Dot longitudinal comparisons of personality development in preschool children. 19 preschool children were administered the IES Arrow-Dot test at the beginning and end of the school year and results compared with those based on a similar sample gathered the previous year. Trends for declining Impulsivity and Superego development were corroborated. Baselines for Impulsivity and Superego showed variation. Baselines and trends of rising Ego scores were supported. Results suggested suport for developmental trends of personality integration in preschool children."} {"id": "PMID:1272741", "title": "Exercise-produced arousal, film-induced arousal and attribution of internal state.", "content": "Respiration rates were monitored on 20 high-anxious and 20 low-anxious female Ss while they were watching an anxiety-provoking film on industrial accidents. Half of the Ss exercised on a bicycle while half remained seated throughout their viewing of the film. Exercised Ss reported feeling less anxious while viewing the accidents compared with the inactive controls. All groups recalled similiar amounts of the film content, and respiration rates did not increase while viewing the accidents. Results of self-report of anxiety are consistent with a recently advanced theory of objective self-awareness.", "contents": "Exercise-produced arousal, film-induced arousal and attribution of internal state. Respiration rates were monitored on 20 high-anxious and 20 low-anxious female Ss while they were watching an anxiety-provoking film on industrial accidents. Half of the Ss exercised on a bicycle while half remained seated throughout their viewing of the film. Exercised Ss reported feeling less anxious while viewing the accidents compared with the inactive controls. All groups recalled similiar amounts of the film content, and respiration rates did not increase while viewing the accidents. Results of self-report of anxiety are consistent with a recently advanced theory of objective self-awareness."} {"id": "PMID:1272742", "title": "Internal-external locus of control and performance on a vigilance task.", "content": "Previous studies have demonstrated there are large individual differences in subjects' ability to perform on vigilance or watch-keeping tasks. This study used Rotter's Internal-External (I-E) Locus of Control Scale to resolve some of the variance attributed to individual differences and tested the hypothesis that the internally controlled person is a better monitor on a vigilance task than an externally controlled person. There were 64 subjects who performed a visual watch-keeping task for a 1-hr. period. The results indicated that the external subjects made significantly more incorrect responses and missed significantly more signals during the entire task. The internal-external dimension was effective in differentiating performance on a vigilance task.", "contents": "Internal-external locus of control and performance on a vigilance task. Previous studies have demonstrated there are large individual differences in subjects' ability to perform on vigilance or watch-keeping tasks. This study used Rotter's Internal-External (I-E) Locus of Control Scale to resolve some of the variance attributed to individual differences and tested the hypothesis that the internally controlled person is a better monitor on a vigilance task than an externally controlled person. There were 64 subjects who performed a visual watch-keeping task for a 1-hr. period. The results indicated that the external subjects made significantly more incorrect responses and missed significantly more signals during the entire task. The internal-external dimension was effective in differentiating performance on a vigilance task."} {"id": "PMID:1272743", "title": "Eye movements in response to real and apparent motions of acoustic targets.", "content": "Monitoring of eye movements resulting from the tracking of sound displacements in total darkness confirmed the generally accepted idea that smooth pursuit cannot be induced in the absence of a real visible target. Exclusively saccadic movements were obtained with real and apparent displacements of a constant frequency source and with frequency variations associated to spatially calibrated positions through training for 5 Ss. Smooth pursuit eye movements were only observed if S was allowed to point and follow with his hand the perceived position of acoustic targets.", "contents": "Eye movements in response to real and apparent motions of acoustic targets. Monitoring of eye movements resulting from the tracking of sound displacements in total darkness confirmed the generally accepted idea that smooth pursuit cannot be induced in the absence of a real visible target. Exclusively saccadic movements were obtained with real and apparent displacements of a constant frequency source and with frequency variations associated to spatially calibrated positions through training for 5 Ss. Smooth pursuit eye movements were only observed if S was allowed to point and follow with his hand the perceived position of acoustic targets."} {"id": "PMID:1272744", "title": "Cultural deprivation and the relative preferences of preschool children for complex and novel stimuli.", "content": "To determine their relative effects, the preferences of 19 deprived and 21 non-deprived preschoolers for both complex stimuli and novel stimuli was measured. The deprived children showed a lack of preference for the novel stimuli but did not differ from the non-deprived group in their preference for complexity. These data clarified a confounding of these stimulus dimensions which had occurred in previous studies.", "contents": "Cultural deprivation and the relative preferences of preschool children for complex and novel stimuli. To determine their relative effects, the preferences of 19 deprived and 21 non-deprived preschoolers for both complex stimuli and novel stimuli was measured. The deprived children showed a lack of preference for the novel stimuli but did not differ from the non-deprived group in their preference for complexity. These data clarified a confounding of these stimulus dimensions which had occurred in previous studies."} {"id": "PMID:1272745", "title": "Preferred hand and steadiness of reaction time.", "content": "RT and its left/right difference of both biceps muscles were measured by electromyogram (EMG) in the bilateral simultaneous flexion of elbows using 11 left- and 13 right-handed subjects under four conditions which were combinations of two factors; warning signal; presence or absence of a fore-period, and position of limbs; elbow 90 degrees or 135 degrees. EMG-RT and its left/right difference were influenced by these factors. The effects of warning and position of limbs were not the same on the preferred and non-preferred hands. It was assumed that EMG-RTs of biceps in the preferred hand were less influenced by these experimental conditions.", "contents": "Preferred hand and steadiness of reaction time. RT and its left/right difference of both biceps muscles were measured by electromyogram (EMG) in the bilateral simultaneous flexion of elbows using 11 left- and 13 right-handed subjects under four conditions which were combinations of two factors; warning signal; presence or absence of a fore-period, and position of limbs; elbow 90 degrees or 135 degrees. EMG-RT and its left/right difference were influenced by these factors. The effects of warning and position of limbs were not the same on the preferred and non-preferred hands. It was assumed that EMG-RTs of biceps in the preferred hand were less influenced by these experimental conditions."} {"id": "PMID:1272746", "title": "Evidence from mutual masking for serial processing of tachistoscopic letter patterns.", "content": "This experiment deomonstrates serial processing of tachistoscopic patterns when all potential artifacts are eliminated. Two nonsense arrays of six letters were tachistoscopically exposed successively at the same positions. Ss identified more letters from the temporally first string on the left of fixation and more from the second on the right, indicating left-to-right serial processing. Variations among Ss in the location of the crossover in curves indicate individual differences in processing time. Therefore, this study demonstrates definitively that tachistoscopic performance at various positions can reflect a sequential left-to-right processing of information, possibly at different rates.", "contents": "Evidence from mutual masking for serial processing of tachistoscopic letter patterns. This experiment deomonstrates serial processing of tachistoscopic patterns when all potential artifacts are eliminated. Two nonsense arrays of six letters were tachistoscopically exposed successively at the same positions. Ss identified more letters from the temporally first string on the left of fixation and more from the second on the right, indicating left-to-right serial processing. Variations among Ss in the location of the crossover in curves indicate individual differences in processing time. Therefore, this study demonstrates definitively that tachistoscopic performance at various positions can reflect a sequential left-to-right processing of information, possibly at different rates."} {"id": "PMID:1272756", "title": "Studies on age specific leukocyte and lymphocyte counts in normal Friesian, Red Danish and Jersey cattle in Denmark.", "content": "To determine reference values for leukocyte and lymphocyte counts of the most common cattle breeds in Denmark, especially regarding the evaluation procedure in the leukosis control work, blood samples from normal cattle of all ages within the Friesian, the Red Danish and the Jersey breeds were collected, transported and counted as in the routine leukosis control programme. Evaluation of breed- and age specific counts showed numerically small, but statistically significant differences in mean values of leukocytes and lymphocytes between on the one hand Jersey cattle and on the other hand Red Danish and Friesian cattle. However, it was found that the key values used in the leukosis control work are generally in good agreement with the calculated 99.87 percentiles of all age- and breed specific lymphocyte count distributions, which were approximated with logarithmic normal distribution curves.", "contents": "Studies on age specific leukocyte and lymphocyte counts in normal Friesian, Red Danish and Jersey cattle in Denmark. To determine reference values for leukocyte and lymphocyte counts of the most common cattle breeds in Denmark, especially regarding the evaluation procedure in the leukosis control work, blood samples from normal cattle of all ages within the Friesian, the Red Danish and the Jersey breeds were collected, transported and counted as in the routine leukosis control programme. Evaluation of breed- and age specific counts showed numerically small, but statistically significant differences in mean values of leukocytes and lymphocytes between on the one hand Jersey cattle and on the other hand Red Danish and Friesian cattle. However, it was found that the key values used in the leukosis control work are generally in good agreement with the calculated 99.87 percentiles of all age- and breed specific lymphocyte count distributions, which were approximated with logarithmic normal distribution curves."} {"id": "PMID:1272758", "title": "The effect of storage temperature on the second day methylene-blue test.", "content": "The purpose was to show whether or not the methylene-blue test can be postponed to the second day. The milk samples were preserved at three different temperatures 8-10 degrees C, 5-7 degrees C and 2-4 degrees C and the storage time was 16-22 hours. The test indicated that the methylene-blue test could be postponed to the next day satisfying the practical needs if the samples were kept at temperature of 2-4 degrees C. At this temperature the results of the second day methylene-blue test differed statistically not more than p less than 0.05 (nearly significant) from the results of the first day methylene-blue test and the percentage of quality class changes was 2.9.", "contents": "The effect of storage temperature on the second day methylene-blue test. The purpose was to show whether or not the methylene-blue test can be postponed to the second day. The milk samples were preserved at three different temperatures 8-10 degrees C, 5-7 degrees C and 2-4 degrees C and the storage time was 16-22 hours. The test indicated that the methylene-blue test could be postponed to the next day satisfying the practical needs if the samples were kept at temperature of 2-4 degrees C. At this temperature the results of the second day methylene-blue test differed statistically not more than p less than 0.05 (nearly significant) from the results of the first day methylene-blue test and the percentage of quality class changes was 2.9."} {"id": "PMID:1272760", "title": "[Angioneurotic hereditary edema. 3 faimilial cases].", "content": "The study involved three families with hane. This disorder differs from the simple condition by its preferential visceral localisation (digestive and, above all, the glottis), its hereditary nature and the existence of a biological abnormality affecting the serum complement system (absence of enzyme activity of C1 esterase inhibitor in the serum of sufferers). The cases reported illustrate the serious prognosis of this condition (four deaths by asphyxia in one family) in the absence of specific therapy. This disorder, although rare, represents a fundamental problem in general pathology by virtue of the enzymatic, immunological and genetic processes which it involves.", "contents": "[Angioneurotic hereditary edema. 3 faimilial cases]. The study involved three families with hane. This disorder differs from the simple condition by its preferential visceral localisation (digestive and, above all, the glottis), its hereditary nature and the existence of a biological abnormality affecting the serum complement system (absence of enzyme activity of C1 esterase inhibitor in the serum of sufferers). The cases reported illustrate the serious prognosis of this condition (four deaths by asphyxia in one family) in the absence of specific therapy. This disorder, although rare, represents a fundamental problem in general pathology by virtue of the enzymatic, immunological and genetic processes which it involves."} {"id": "PMID:1272771", "title": "[Correlation between immunological stage and response to chemotherapy. Results in 64 patients with nonresectable epidermoid bronchial cancers].", "content": "Out of 64 patients with non resectable epidermal bronchus carcinoma, 26 patients had before any treatment positive responses of skin tests to recall antigens. In these patients we found a correlation between the reactivity of the skin tests, the presence of seric factor inhibiting the leucocyte migration, the mean count of peripheral lymphocytes and the response to combination chemotherapy protocol. The patients who respond to treatment have a significantly better prognosis than the patients who do not respond. With this correlation it seems to be possible to distinguish between two populations of patients with non resectable bronchus carcinoma : one population with a good risk who can be significantly improved by the treatment : the other population with a very severe prognosis.", "contents": "[Correlation between immunological stage and response to chemotherapy. Results in 64 patients with nonresectable epidermoid bronchial cancers]. Out of 64 patients with non resectable epidermal bronchus carcinoma, 26 patients had before any treatment positive responses of skin tests to recall antigens. In these patients we found a correlation between the reactivity of the skin tests, the presence of seric factor inhibiting the leucocyte migration, the mean count of peripheral lymphocytes and the response to combination chemotherapy protocol. The patients who respond to treatment have a significantly better prognosis than the patients who do not respond. With this correlation it seems to be possible to distinguish between two populations of patients with non resectable bronchus carcinoma : one population with a good risk who can be significantly improved by the treatment : the other population with a very severe prognosis."} {"id": "PMID:1272772", "title": "[Arterial embolization in the treatment of metrorrhagia of tumoral origin].", "content": "The authors report two cases of embolisation of the genital arteries in patients suffering from emtrorrhagia due to a tumour and in whom surgical treatment was impossible. The results of embolisation were satisfactory.", "contents": "[Arterial embolization in the treatment of metrorrhagia of tumoral origin]. The authors report two cases of embolisation of the genital arteries in patients suffering from emtrorrhagia due to a tumour and in whom surgical treatment was impossible. The results of embolisation were satisfactory."} {"id": "PMID:1272773", "title": "[Substitutive treatment of hemopjolia A using a new factor VIII concentrate].", "content": "Thirty children with classical hemophilia were treated with an intermediate-purity factor VIII concentrate prepared according to Newman. The average factor VIII concentration was 21 U/ml. Thirty five injections ranging from 3 to 55 U/kg of body weight were given. The clinical efficacy was satisfactory, no side effects were observed. In vivo factor VIII recovery was initially very high, decreased rapidly until the 4th hour post infusion and then slowed according to a biological half-life of 11.3 +/- 3.1 hours. A satisfactory correlation between the dose injected and the factor VIII in vivo recovery was observed only after four hours post injection. The commercially available concentrate contains in average 25 U of factor VIII per ml, 13 U/mg of fibrinogen and 2.03 U/mg of proteins. It can be injected with a seringe and is therefore adapted to home care treatment. In addition, it is convenient for prolonged treatment with high doses of factor VIII as required by surgical procedure of treatment of patients with an inhibitor, avoiding limitations caused by hypervolemia or hyperfibrinogenemia.", "contents": "[Substitutive treatment of hemopjolia A using a new factor VIII concentrate]. Thirty children with classical hemophilia were treated with an intermediate-purity factor VIII concentrate prepared according to Newman. The average factor VIII concentration was 21 U/ml. Thirty five injections ranging from 3 to 55 U/kg of body weight were given. The clinical efficacy was satisfactory, no side effects were observed. In vivo factor VIII recovery was initially very high, decreased rapidly until the 4th hour post infusion and then slowed according to a biological half-life of 11.3 +/- 3.1 hours. A satisfactory correlation between the dose injected and the factor VIII in vivo recovery was observed only after four hours post injection. The commercially available concentrate contains in average 25 U of factor VIII per ml, 13 U/mg of fibrinogen and 2.03 U/mg of proteins. It can be injected with a seringe and is therefore adapted to home care treatment. In addition, it is convenient for prolonged treatment with high doses of factor VIII as required by surgical procedure of treatment of patients with an inhibitor, avoiding limitations caused by hypervolemia or hyperfibrinogenemia."} {"id": "PMID:1272793", "title": "Function of DNA polymerase I in RNA-primed synthesis of bacteriophage M-13 duplex DNA.", "content": "Cell-free extracts from Escherichia coli contain a DNA polymerase activity resistant to SH-blocking agents, which is capable of synthesizing complementary strand DNA on a circular M-13 DNA template by extension of RNA primers. This activity is considered to be identical with DNA polymerase I (or some altered form of this enzyme) since it is missing in extracts from po1A- cells. DNA synthesis in the presence of SH-blocking agents occurs at a reduced rate as compared to untreated controls and leads to the formation of DNA chains of defined size (0.4-0.5 genome's length). It is concluded that efficient M-13 duplex DNA synthesis requires the cooperation of both DNA polymerase I and III.", "contents": "Function of DNA polymerase I in RNA-primed synthesis of bacteriophage M-13 duplex DNA. Cell-free extracts from Escherichia coli contain a DNA polymerase activity resistant to SH-blocking agents, which is capable of synthesizing complementary strand DNA on a circular M-13 DNA template by extension of RNA primers. This activity is considered to be identical with DNA polymerase I (or some altered form of this enzyme) since it is missing in extracts from po1A- cells. DNA synthesis in the presence of SH-blocking agents occurs at a reduced rate as compared to untreated controls and leads to the formation of DNA chains of defined size (0.4-0.5 genome's length). It is concluded that efficient M-13 duplex DNA synthesis requires the cooperation of both DNA polymerase I and III."} {"id": "PMID:1272794", "title": "New phosphoramidates as protecting groups in ribooligonucleotides synthesis.", "content": "N, N-Dimethyl-p-phenylenediamine, glycine amide and p-methylthioaniline were condensed with uridine 5'-phosphate and the phosphoramidates obtained were tested for their stability in anhydrous pyridine, 50% aqueous pyridine or 80% acetic acid. The p-methylthioanilidate (IIc) was oxidized to give p-methylsulfoxylanilidate of uridine 5'-phosphate (IId) which was found to be 5 times more stable than the p-methylthio compound. The p-methylsulfoxylanilidate of 2'-O-benzoyluridine 3'-phosphate was condensed with the mononucleotide to yield the dinucleotide, MMTrU(OBz)-p-U(OBz)-p in 28% yield.", "contents": "New phosphoramidates as protecting groups in ribooligonucleotides synthesis. N, N-Dimethyl-p-phenylenediamine, glycine amide and p-methylthioaniline were condensed with uridine 5'-phosphate and the phosphoramidates obtained were tested for their stability in anhydrous pyridine, 50% aqueous pyridine or 80% acetic acid. The p-methylthioanilidate (IIc) was oxidized to give p-methylsulfoxylanilidate of uridine 5'-phosphate (IId) which was found to be 5 times more stable than the p-methylthio compound. The p-methylsulfoxylanilidate of 2'-O-benzoyluridine 3'-phosphate was condensed with the mononucleotide to yield the dinucleotide, MMTrU(OBz)-p-U(OBz)-p in 28% yield."} {"id": "PMID:1272795", "title": "The effective synthesis of uridylyl/3'-5'/5-methylcytidylyl/3'-5'/guanosine.", "content": "The triester method was adapted to the synthesis of uridylyl/3'-5'/5-methylcytidylyl/3'-5'/guanosine. As the protecting groups 4-methoxy-5,6-dihydro-2H-pyran for 2'-OH and 5'-OH groups of uridine and 2'-OH group of 5-methylcytidine, methoxymethylidene for I:3'-cis-diol system of guanosine, and benzoyl for the amino groups of 5-methylcytidine and guanosine were used. The obtained product was characterised by UV, electrophoresis, chromatography, an enzymatic digestion and alkaline hydrolysis.", "contents": "The effective synthesis of uridylyl/3'-5'/5-methylcytidylyl/3'-5'/guanosine. The triester method was adapted to the synthesis of uridylyl/3'-5'/5-methylcytidylyl/3'-5'/guanosine. As the protecting groups 4-methoxy-5,6-dihydro-2H-pyran for 2'-OH and 5'-OH groups of uridine and 2'-OH group of 5-methylcytidine, methoxymethylidene for I:3'-cis-diol system of guanosine, and benzoyl for the amino groups of 5-methylcytidine and guanosine were used. The obtained product was characterised by UV, electrophoresis, chromatography, an enzymatic digestion and alkaline hydrolysis."} {"id": "PMID:1272796", "title": "Analysis of the possible helical structures of nucleic acids and polynucleotides. Application of (n-h) plots.", "content": "The two helical parameters n and h where n is the number of nucleotide residues per turn and h is the height per nucleotide residue have been evaluated for single stranded helical polynucleotide chains comprising C(3') -endo and C(2') endo class of nucleotides. The helical parameters are found to be especially sensitive to the C(4')-C(3') (sugar pucker) and the C(4')-C(5') torsions. The (n-h) plots display only one important helix forming domain for each class of nucleotides characterized by the sugar pucker and the C(4')-C(5') torsion. A correlation between the (n-h) plots and the known RNA (A,A') and DNA (A,B,C) helical forms has been established. It is found that all forms of helices except the C-DNA possess a favorable combination of P-O torsions. The analysis of the (n-h) plots suggests that C-DNA can have a conformation very similar to B-DNA. Although the (n-h) plots predict the stereochemical possibility of both right-handed and left-handed helices, nucleic acids apparently prefer right-handed conformation because of the energetics associated with the sugar-phosphate backbone and the base.", "contents": "Analysis of the possible helical structures of nucleic acids and polynucleotides. Application of (n-h) plots. The two helical parameters n and h where n is the number of nucleotide residues per turn and h is the height per nucleotide residue have been evaluated for single stranded helical polynucleotide chains comprising C(3') -endo and C(2') endo class of nucleotides. The helical parameters are found to be especially sensitive to the C(4')-C(3') (sugar pucker) and the C(4')-C(5') torsions. The (n-h) plots display only one important helix forming domain for each class of nucleotides characterized by the sugar pucker and the C(4')-C(5') torsion. A correlation between the (n-h) plots and the known RNA (A,A') and DNA (A,B,C) helical forms has been established. It is found that all forms of helices except the C-DNA possess a favorable combination of P-O torsions. The analysis of the (n-h) plots suggests that C-DNA can have a conformation very similar to B-DNA. Although the (n-h) plots predict the stereochemical possibility of both right-handed and left-handed helices, nucleic acids apparently prefer right-handed conformation because of the energetics associated with the sugar-phosphate backbone and the base."} {"id": "PMID:1272797", "title": "The methylation of adenovirus-specific nuclear and cytoplasmic RNA.", "content": "Each poly(A) containing cytoplasmic AD-2 MRNA contains at its 5' terminus the general structure m7 GpppN1 pN2p or m7 GpppN1mpN2mpNp as well as an average of 4 m6A and 0.5-1 m5C residues per molecule. Almost all of the N1m residues are adenine derivatives including Am, m6Am and probably m26,6Am. The N2m is mostly Cm but small amounts of the other three methylated bases are also present. All the methylated constitutents of mRNA are distant from the 3' terminal poly(A). The amount of m6A appears to be greater in larger mRNA than in smaller mRNA. Nuclear Ad-2 specific RNA also contains caps, m6A, and m5C with about twice as much m6A relative to caps as cytoplasmic mRNA. The similarity of Ad-2 nuclear and mRNA to HeLa hnRNA and mRNA suggests that adenovirus mRNA production is a good model for eukaryotic mRNA production.", "contents": "The methylation of adenovirus-specific nuclear and cytoplasmic RNA. Each poly(A) containing cytoplasmic AD-2 MRNA contains at its 5' terminus the general structure m7 GpppN1 pN2p or m7 GpppN1mpN2mpNp as well as an average of 4 m6A and 0.5-1 m5C residues per molecule. Almost all of the N1m residues are adenine derivatives including Am, m6Am and probably m26,6Am. The N2m is mostly Cm but small amounts of the other three methylated bases are also present. All the methylated constitutents of mRNA are distant from the 3' terminal poly(A). The amount of m6A appears to be greater in larger mRNA than in smaller mRNA. Nuclear Ad-2 specific RNA also contains caps, m6A, and m5C with about twice as much m6A relative to caps as cytoplasmic mRNA. The similarity of Ad-2 nuclear and mRNA to HeLa hnRNA and mRNA suggests that adenovirus mRNA production is a good model for eukaryotic mRNA production."} {"id": "PMID:1272798", "title": "Tritium labelling of nucleic acids accompanied by conversion of cytosine to uracil.", "content": "A new method of incorporation of tritium into nucleic acids with an accompanying conversion of cytosine to uracil is proposed. The method is based on the reaction of nucleic acids with bisulfite in the presence of 3H2O. Under certain conditions poly(C) is quantitatively converted to a radioactive poly(U), whereas similar bisulfite treatment of poly(U) does not result in any tritium incorporation. Specificity of the reaction is confirmed by the results of analysis of modified tRNA and rRNA. Incubation of tRNA with bisulfite and 3H2O does not lead to cleavage of the polynucleotide chain. Similar treatment of the denatured DNA results in tritium incorporation into DNA which is accompanied by a conversion of cytosine to uracil. There is virtually no reaction between native DNA and bisulfite. Only certain cytosone residues in yeast tRNAVal/2a interact with bisulfate providing that reaction is carried out under sufficiently mild conditions.", "contents": "Tritium labelling of nucleic acids accompanied by conversion of cytosine to uracil. A new method of incorporation of tritium into nucleic acids with an accompanying conversion of cytosine to uracil is proposed. The method is based on the reaction of nucleic acids with bisulfite in the presence of 3H2O. Under certain conditions poly(C) is quantitatively converted to a radioactive poly(U), whereas similar bisulfite treatment of poly(U) does not result in any tritium incorporation. Specificity of the reaction is confirmed by the results of analysis of modified tRNA and rRNA. Incubation of tRNA with bisulfite and 3H2O does not lead to cleavage of the polynucleotide chain. Similar treatment of the denatured DNA results in tritium incorporation into DNA which is accompanied by a conversion of cytosine to uracil. There is virtually no reaction between native DNA and bisulfite. Only certain cytosone residues in yeast tRNAVal/2a interact with bisulfate providing that reaction is carried out under sufficiently mild conditions."} {"id": "PMID:1272799", "title": "Base composition heterogeneity of mammalian DNAs in CsCl-netropsin density gradient.", "content": "DNAs of 15 mammals and some lower organisms were analysed by CsCl-netropsin density gradient centrifugation. Increased resolving power of this method enabled to detect many new components in mammalian DNAs. Distinct components were detected in the density range of the main band. These components found in different mammalian DNAs have probably limited variation in the G+C content. Most of other components seems to be species specific. The DNAs of lower organisms form homogeneous band even in the presence of netropsin. The relation between densities in CsCl-netropsin and CsCl density gradient is nonlinear. This result supports a hypothesis that in high ionic strength netropsin is preferentially bound to (dA.dT) clusters.", "contents": "Base composition heterogeneity of mammalian DNAs in CsCl-netropsin density gradient. DNAs of 15 mammals and some lower organisms were analysed by CsCl-netropsin density gradient centrifugation. Increased resolving power of this method enabled to detect many new components in mammalian DNAs. Distinct components were detected in the density range of the main band. These components found in different mammalian DNAs have probably limited variation in the G+C content. Most of other components seems to be species specific. The DNAs of lower organisms form homogeneous band even in the presence of netropsin. The relation between densities in CsCl-netropsin and CsCl density gradient is nonlinear. This result supports a hypothesis that in high ionic strength netropsin is preferentially bound to (dA.dT) clusters."} {"id": "PMID:1272800", "title": "The binding of poly(rA) and poly(rU) to denatured DNA. I. Model studies with homopolymers.", "content": "We have compared the properties of the poly(rA).oligo(dT) complex with those of the poly(rU).oligo(dA)n complex. Three main differences were found. First, poly(rA) and oligo(dT)n do not form a complex in concentrations of CsCl exceeding 2 M because the poly(rA) is insoluble in high salt. If the complex is made in low salt, it is destabilized if the CsCl concentration is raised. Complexes between poly(rU) and oligo(dA)n, on the other hand, can be formed in CsCl concentrations up to 6.6 M. Second, complexes between poly(rA) and oligo(dT)n are more rapidly destabilized with decreasing chain length than complexes between poly(rU) and oligo(dA)n. Third, the density of the complex between poly(rA) and poly(dT) in CsCl is slightly lower than that of poly(dT), whereas the density of the complex between poly(rU) and poly(dA) in CsCl is at least 300 g/cm3 higher than that of poly(dA). These results explain why denatured natural DNAs that bind poly(rU) in a CsCl gradient usually do not bind poly(rA).", "contents": "The binding of poly(rA) and poly(rU) to denatured DNA. I. Model studies with homopolymers. We have compared the properties of the poly(rA).oligo(dT) complex with those of the poly(rU).oligo(dA)n complex. Three main differences were found. First, poly(rA) and oligo(dT)n do not form a complex in concentrations of CsCl exceeding 2 M because the poly(rA) is insoluble in high salt. If the complex is made in low salt, it is destabilized if the CsCl concentration is raised. Complexes between poly(rU) and oligo(dA)n, on the other hand, can be formed in CsCl concentrations up to 6.6 M. Second, complexes between poly(rA) and oligo(dT)n are more rapidly destabilized with decreasing chain length than complexes between poly(rU) and oligo(dA)n. Third, the density of the complex between poly(rA) and poly(dT) in CsCl is slightly lower than that of poly(dT), whereas the density of the complex between poly(rU) and poly(dA) in CsCl is at least 300 g/cm3 higher than that of poly(dA). These results explain why denatured natural DNAs that bind poly(rU) in a CsCl gradient usually do not bind poly(rA)."} {"id": "PMID:1272801", "title": "The binding of poly (rA) and poly (rU) to denatured DNA. II. Studies with natural DNAs.", "content": "We have studied the interaction of poly(rA) and poly(rU) with natural DNAs containing (dA.dT)n sequences. The results indicate that hybridization of poly(rA) to denatured DNA can be used to estimate the size and frequency of large (dA.dT)n tracts, whereas hybridization with poly(rU) does not give reliable information on these points. In 6.6 M CsCl, poly(rU) can form stable complexes with denatured DNA containing short (dA)n tracts (n less than or equal to 6), whereas binding of poly(rA) to denatured DNA under these conditions requires much larger (dT)n tracts (estimated n greater than 13). Moreover, binding of poly(rA) requires pre-hybridization in low salt, because free poly(rA) precipitates in 6.6 M CsCl.", "contents": "The binding of poly (rA) and poly (rU) to denatured DNA. II. Studies with natural DNAs. We have studied the interaction of poly(rA) and poly(rU) with natural DNAs containing (dA.dT)n sequences. The results indicate that hybridization of poly(rA) to denatured DNA can be used to estimate the size and frequency of large (dA.dT)n tracts, whereas hybridization with poly(rU) does not give reliable information on these points. In 6.6 M CsCl, poly(rU) can form stable complexes with denatured DNA containing short (dA)n tracts (n less than or equal to 6), whereas binding of poly(rA) to denatured DNA under these conditions requires much larger (dT)n tracts (estimated n greater than 13). Moreover, binding of poly(rA) requires pre-hybridization in low salt, because free poly(rA) precipitates in 6.6 M CsCl."} {"id": "PMID:1272802", "title": "3-Ribosyl-6-methyluracil as a phosphate acceptor in the synthesis of the internucleotide bond catalyzed by pancreatic ribonuclease.", "content": "The synthesis of uridylyl-(3'-5')-3-ribosyl-6-methyluracil (UprmU) catalyzed by pancreatic ribonuclease (EC 3.4.1.22) has been performed using uridine 2', 3'-cyclic phosphate (U greater than p) as phosphate donor and 3-ribosyl-6-methyluracil (rmU) as phosphate acceptor. The rate of synthesis of UprmU is much higher than that of uridylyl-(3'-5')-uridine (UpU) in a control experiment under the same conditions with uridine as acceptor. The yields of UpU and UprmU were 20 and 17% respectively. The competitive hydrolysis of the initial U greater than p also proceeds faster when rmU is used as the acceptor. The relationship between the conformation of this nucleoside and its acceptor activity in the enzymatic synthesis of the internucleotide bond is discussed.", "contents": "3-Ribosyl-6-methyluracil as a phosphate acceptor in the synthesis of the internucleotide bond catalyzed by pancreatic ribonuclease. The synthesis of uridylyl-(3'-5')-3-ribosyl-6-methyluracil (UprmU) catalyzed by pancreatic ribonuclease (EC 3.4.1.22) has been performed using uridine 2', 3'-cyclic phosphate (U greater than p) as phosphate donor and 3-ribosyl-6-methyluracil (rmU) as phosphate acceptor. The rate of synthesis of UprmU is much higher than that of uridylyl-(3'-5')-uridine (UpU) in a control experiment under the same conditions with uridine as acceptor. The yields of UpU and UprmU were 20 and 17% respectively. The competitive hydrolysis of the initial U greater than p also proceeds faster when rmU is used as the acceptor. The relationship between the conformation of this nucleoside and its acceptor activity in the enzymatic synthesis of the internucleotide bond is discussed."} {"id": "PMID:1272803", "title": "Sepcific fragmentation of DNA heteroduplex molecules of two bacteriophage lambda mutants with endonuclease Si from Aspergillus oryzae.", "content": "Heteroduplex DNA molecules of two bacteriophage mutants (lambda b2 and lambda i434ct68) were obtained by the method of molecular hybridization. These heteroduplexes possessed two types of loops formed as a result of: a) deletion in one of the DNA strands; and b) substitution of a DNA fragment for nonhomological one. The digestion of heteroduplexes with single-stranded specific nuclease SI from Aspergillus oryzae produced two fragments at 37 degrees C and three ones at 55 degrees C. The separation of fragments and determination of their molecular weight were carried out by means of electrophoresis in agarose. The molecular weights both measured and preliminarily calculated proved to be close. One of the fragments was identificated by its biological activity in CaCl2-dependent infectious system with helperphage.", "contents": "Sepcific fragmentation of DNA heteroduplex molecules of two bacteriophage lambda mutants with endonuclease Si from Aspergillus oryzae. Heteroduplex DNA molecules of two bacteriophage mutants (lambda b2 and lambda i434ct68) were obtained by the method of molecular hybridization. These heteroduplexes possessed two types of loops formed as a result of: a) deletion in one of the DNA strands; and b) substitution of a DNA fragment for nonhomological one. The digestion of heteroduplexes with single-stranded specific nuclease SI from Aspergillus oryzae produced two fragments at 37 degrees C and three ones at 55 degrees C. The separation of fragments and determination of their molecular weight were carried out by means of electrophoresis in agarose. The molecular weights both measured and preliminarily calculated proved to be close. One of the fragments was identificated by its biological activity in CaCl2-dependent infectious system with helperphage."} {"id": "PMID:1272804", "title": "On the possibility of excimer state formation in homodimers of the pyrimidine bases.", "content": "A detailed investigation of the ground state and the first excited state of the pyrimidine bases of uracil, cytosine, thymine and their stacked homodimers is carried out by the Extended H\u00fcckel method. The first exicted state is shown to be the (see article)-state. The excitation is localized mainly on the C5-C6 bond region. The energy dependence of the ground state and the first excited state of the homodimers on the mutual position of bases is considered. For every dimer a minimum on the exicted state potential curve is found. This fact creates the possibility for the formation of excimer. The obtained data give some reason for the suggestion about participation of the excimer state as a precursor of photodimer.", "contents": "On the possibility of excimer state formation in homodimers of the pyrimidine bases. A detailed investigation of the ground state and the first excited state of the pyrimidine bases of uracil, cytosine, thymine and their stacked homodimers is carried out by the Extended H\u00fcckel method. The first exicted state is shown to be the (see article)-state. The excitation is localized mainly on the C5-C6 bond region. The energy dependence of the ground state and the first excited state of the homodimers on the mutual position of bases is considered. For every dimer a minimum on the exicted state potential curve is found. This fact creates the possibility for the formation of excimer. The obtained data give some reason for the suggestion about participation of the excimer state as a precursor of photodimer."} {"id": "PMID:1272805", "title": "Interpretation of the properties of chromatin extracts from mammalian nuclei.", "content": "Chromatin from standard preparations of nuclei stabilized by magnesium ions at 0-4 degrees C was degraded during the nuclear isolation, and newly-synthesized chromatin was degraded slightly more slowly than the ;older' chromatin. The significance of this observation, and its relation to the interpretation of the properties of nucleoprotein extracts is discussed.", "contents": "Interpretation of the properties of chromatin extracts from mammalian nuclei. Chromatin from standard preparations of nuclei stabilized by magnesium ions at 0-4 degrees C was degraded during the nuclear isolation, and newly-synthesized chromatin was degraded slightly more slowly than the ;older' chromatin. The significance of this observation, and its relation to the interpretation of the properties of nucleoprotein extracts is discussed."} {"id": "PMID:1272806", "title": "2',3'=Carbonates in the synthesis of uridine 5'-deoxy and 2',5'-dideoxy derivatives.", "content": "Detritylation of 2',3'-O-carbonyl-5'-O-trityluridine (Ia) with ethereal hydrogen chloride affords 2',3'-O-carbonyluridine (Ib; 83%) which is converted by mesylation to the 5'-mesylcarbonate Ic (75%). Reaction of compound, Ic with tetrabutylammonium bromide in DMF affords the 5'-bromo carbonate Id (77%) which is reduced with tributyltin hydride to the 5'-deoxyuridine 2',3'-cyclic carbonate Ie (70%). When heated with imidazole, compound Ie affords the 2,2'-anhydro derivative IIa (76%) which is converted to the 2'-chloro derivative IIIa (88%) on heating with HC1/DMF. The tributyltin hydride reduction of compound IIIa gives 2',5'-dideoxyuridine (IIIb; 68%). When heated with NaHCO3 in DMF, the 5'-bromo carbonate Id affords the anhydro bromo derivative IIb (50%) which is converted to the 2',5'-dichloro derivative IIIc (86%) on heating with HC1/DMF. The tributyltin hydride reduction of compound IIIc affords the 2',5'-dideoxy derivative IIIb (59%). Alkaline hydrolysis of the 2,2'-anhydro derivative IIa affords the arabinosyl derivative IVa which is converted to the diacetyl derivative IVb (34%) by acetylation. When refluxed in water, the 2',3'-cyclic carbonates Ib, Id, and Ie are hydrolysed to the parent nucleosides, namely, uridine (Va; 81%), 5'-bromo-5'-deoxyuridine (Vb; 78%), and 5'-deoxyuridine (Vc; 83%). Hydrolysis of carbonates Ib and Ie is accompanied by the formation of the 2,2'-anhydro derivatives IIc (10%) and IIa (5%) as by-products.", "contents": "2',3'=Carbonates in the synthesis of uridine 5'-deoxy and 2',5'-dideoxy derivatives. Detritylation of 2',3'-O-carbonyl-5'-O-trityluridine (Ia) with ethereal hydrogen chloride affords 2',3'-O-carbonyluridine (Ib; 83%) which is converted by mesylation to the 5'-mesylcarbonate Ic (75%). Reaction of compound, Ic with tetrabutylammonium bromide in DMF affords the 5'-bromo carbonate Id (77%) which is reduced with tributyltin hydride to the 5'-deoxyuridine 2',3'-cyclic carbonate Ie (70%). When heated with imidazole, compound Ie affords the 2,2'-anhydro derivative IIa (76%) which is converted to the 2'-chloro derivative IIIa (88%) on heating with HC1/DMF. The tributyltin hydride reduction of compound IIIa gives 2',5'-dideoxyuridine (IIIb; 68%). When heated with NaHCO3 in DMF, the 5'-bromo carbonate Id affords the anhydro bromo derivative IIb (50%) which is converted to the 2',5'-dichloro derivative IIIc (86%) on heating with HC1/DMF. The tributyltin hydride reduction of compound IIIc affords the 2',5'-dideoxy derivative IIIb (59%). Alkaline hydrolysis of the 2,2'-anhydro derivative IIa affords the arabinosyl derivative IVa which is converted to the diacetyl derivative IVb (34%) by acetylation. When refluxed in water, the 2',3'-cyclic carbonates Ib, Id, and Ie are hydrolysed to the parent nucleosides, namely, uridine (Va; 81%), 5'-bromo-5'-deoxyuridine (Vb; 78%), and 5'-deoxyuridine (Vc; 83%). Hydrolysis of carbonates Ib and Ie is accompanied by the formation of the 2,2'-anhydro derivatives IIc (10%) and IIa (5%) as by-products."} {"id": "PMID:1272807", "title": "Search for an adenine photoproduct in DNA.", "content": "Poly(d[14C]A), p(dA)2, and [14C]adenosine-labeled DNA were irradiated at 254 nm with fluences up to 50 J/m2, and then following formic acid hydrolysis at 170 degrees C WERE SUBJECTED TO PAPER CHROMAtography using a butanol:water:acetic acid (80:30:12) solvent system. For poly(dA), up to 25% of the radioactivity appeared as fluorescent material located in the Rf 0.21-0.29 region. The hydrolysate of the purified photoproduct, p(dA)2, isolated from irradiated p(dA)2 by DEAE chromatography also had an Rf of 0.29 as well as an absorbance maximum at 310 nm. In all cases studied, however, the photoproduct yield in the Rf 0.29 region for native DNA was less than 2%. Denaturation of the DNA appeared to enhance the yield slightly, although no pronounced peak in this region of the chromatogram was discerned. Mechanistic studies indicate that the yield of the adenine photoproduct in poly(dA) is favored by base stacking, has a singlet excimer as a precursor, and is quenched by hydrogen bonding to a pyrimidine. It is concluded that the yield of the adenine photoproduct in both native and denatured DNA is considerably less than in poly (dA) and in all probability does not represent a biologically significant product.", "contents": "Search for an adenine photoproduct in DNA. Poly(d[14C]A), p(dA)2, and [14C]adenosine-labeled DNA were irradiated at 254 nm with fluences up to 50 J/m2, and then following formic acid hydrolysis at 170 degrees C WERE SUBJECTED TO PAPER CHROMAtography using a butanol:water:acetic acid (80:30:12) solvent system. For poly(dA), up to 25% of the radioactivity appeared as fluorescent material located in the Rf 0.21-0.29 region. The hydrolysate of the purified photoproduct, p(dA)2, isolated from irradiated p(dA)2 by DEAE chromatography also had an Rf of 0.29 as well as an absorbance maximum at 310 nm. In all cases studied, however, the photoproduct yield in the Rf 0.29 region for native DNA was less than 2%. Denaturation of the DNA appeared to enhance the yield slightly, although no pronounced peak in this region of the chromatogram was discerned. Mechanistic studies indicate that the yield of the adenine photoproduct in poly(dA) is favored by base stacking, has a singlet excimer as a precursor, and is quenched by hydrogen bonding to a pyrimidine. It is concluded that the yield of the adenine photoproduct in both native and denatured DNA is considerably less than in poly (dA) and in all probability does not represent a biologically significant product."} {"id": "PMID:1272808", "title": "Modification of end phosphate gruops in mono- and oligonucleotides.", "content": "A method is described for selective activation of phosphomonoester end groups of oligonucleotides and nucleosidedi-(tri) phosphates via mixed anhydrides with mesitoic acid. Mixed anhydrides are synthesized in high yield and isolated by paper or DEAE-cellulose column chromatography. The ability of such anhydrides to phosphorylate different nucleophilic agents was used for synthesis of amidates, imidazolidates, esters, thioesters and pyrophosphates of mono- and oligonucleotides. Mixed anhydrides mono-, oligonucleotides and nucleosidedi-(tri)phosphates and mesitoic acid were also applied to achieve immobilization of the mono- and oligonucleotides via their end groups on hexamethylenediamine - Sepharose support. Mixed anhydrides studied may be efficiently used for affinity labeling of proteins and nucleic acids and also as material for preparating reagents for template reactions.", "contents": "Modification of end phosphate gruops in mono- and oligonucleotides. A method is described for selective activation of phosphomonoester end groups of oligonucleotides and nucleosidedi-(tri) phosphates via mixed anhydrides with mesitoic acid. Mixed anhydrides are synthesized in high yield and isolated by paper or DEAE-cellulose column chromatography. The ability of such anhydrides to phosphorylate different nucleophilic agents was used for synthesis of amidates, imidazolidates, esters, thioesters and pyrophosphates of mono- and oligonucleotides. Mixed anhydrides mono-, oligonucleotides and nucleosidedi-(tri)phosphates and mesitoic acid were also applied to achieve immobilization of the mono- and oligonucleotides via their end groups on hexamethylenediamine - Sepharose support. Mixed anhydrides studied may be efficiently used for affinity labeling of proteins and nucleic acids and also as material for preparating reagents for template reactions."} {"id": "PMID:1272809", "title": "Reaction of diazoalkanes with 1-substituted 2, 4-dioxopyrimidines. Formation of O2, N-3 and O4-alkyl products.", "content": "In non-aqueous solution, diazomethane and diazoethane react with the O2, O4 and N-3 sites of uridine, thymidine, 1-methyluracil and 1-methylthymine. Diazoethane has a higher affinity for alkylating oxygens than does diazomethane. The relative ratio of O2:O4:N-3 methyl products is 1:2:16 and of ethyl products the ratio is 1:1:2. When the diazoethane reaction is performed in neutral buffered solution, the same proportion of O2:O4:N-3 ethyl products is found, but the extent of reaction is very low. O2-alkylation greatly labilizes the glycosidic bond of thymidine and uridine toward acid hydrolysis. All O2 and O4 alkyl 1-substituted 2,4-dioxopyrimidines are dealkylated in weak acid but the O2 alkyl group is the more stable.", "contents": "Reaction of diazoalkanes with 1-substituted 2, 4-dioxopyrimidines. Formation of O2, N-3 and O4-alkyl products. In non-aqueous solution, diazomethane and diazoethane react with the O2, O4 and N-3 sites of uridine, thymidine, 1-methyluracil and 1-methylthymine. Diazoethane has a higher affinity for alkylating oxygens than does diazomethane. The relative ratio of O2:O4:N-3 methyl products is 1:2:16 and of ethyl products the ratio is 1:1:2. When the diazoethane reaction is performed in neutral buffered solution, the same proportion of O2:O4:N-3 ethyl products is found, but the extent of reaction is very low. O2-alkylation greatly labilizes the glycosidic bond of thymidine and uridine toward acid hydrolysis. All O2 and O4 alkyl 1-substituted 2,4-dioxopyrimidines are dealkylated in weak acid but the O2 alkyl group is the more stable."} {"id": "PMID:1272810", "title": "Scintigraphy with 99mTc-tripolyphosphate in the early diagnosis of osteomyelitis.", "content": "In 14 consecutive patients with suspected osteomyelitis studies were performed with 99mTc-tripolyphosphate. In all patients the diagnosis was ultimately verified by biopsy. In seven of the 14 patients the radiograms showed osseous lesions at the same time as the scintigraphic studies. In the other seven patients, such lesions became visible on the X ray film one to 20 weeks after their demonstration by the radioisotope method. 99mTc-tripolyphosphate appears to be a very sensitive indicator of oesteomyelitis.", "contents": "Scintigraphy with 99mTc-tripolyphosphate in the early diagnosis of osteomyelitis. In 14 consecutive patients with suspected osteomyelitis studies were performed with 99mTc-tripolyphosphate. In all patients the diagnosis was ultimately verified by biopsy. In seven of the 14 patients the radiograms showed osseous lesions at the same time as the scintigraphic studies. In the other seven patients, such lesions became visible on the X ray film one to 20 weeks after their demonstration by the radioisotope method. 99mTc-tripolyphosphate appears to be a very sensitive indicator of oesteomyelitis."} {"id": "PMID:1272811", "title": "[Determination of radio-iodine in struma cysts with regard to radio-iodine kinetics].", "content": "After oral administration iodine 131 is demonstrable within hours and days in thyroid cyst fluid. This iodine concentration may be caused by active metabolism in the cyst, depending on thyroid function. Highest levels of iodine 131 are found in autonomous nodules.", "contents": "[Determination of radio-iodine in struma cysts with regard to radio-iodine kinetics]. After oral administration iodine 131 is demonstrable within hours and days in thyroid cyst fluid. This iodine concentration may be caused by active metabolism in the cyst, depending on thyroid function. Highest levels of iodine 131 are found in autonomous nodules."} {"id": "PMID:1272812", "title": "Scintiscan characteristics of normal thyroid gland in a region of known iodine intake.", "content": "Morphological features of a normal thyroid gland in a geographical region where the daily iodine intake is about 1 mg are established. The mean weight of the thyroid gland is 31.3 gm with a range from 19 to 43 gm. Oblique length of the right lobe is 5.0 cm and that of the left lobe 4.8 cm. The surface area of the right and left lobes is 9.7 and 9.1 cm2, respectively. The weight of the thyroid gland calculated on the basis of the scan obtained with 99mTcO4 is quite variable and shows poor correlation (gamma = 0.40) with the weight obtained on the basis of I-131 scan. It is suggested that the criteria of normalcy be established regionally based on iodine intake, and that an isotope of iodine be used in calculating the weight of thyroid gland for dosimetry purposes.", "contents": "Scintiscan characteristics of normal thyroid gland in a region of known iodine intake. Morphological features of a normal thyroid gland in a geographical region where the daily iodine intake is about 1 mg are established. The mean weight of the thyroid gland is 31.3 gm with a range from 19 to 43 gm. Oblique length of the right lobe is 5.0 cm and that of the left lobe 4.8 cm. The surface area of the right and left lobes is 9.7 and 9.1 cm2, respectively. The weight of the thyroid gland calculated on the basis of the scan obtained with 99mTcO4 is quite variable and shows poor correlation (gamma = 0.40) with the weight obtained on the basis of I-131 scan. It is suggested that the criteria of normalcy be established regionally based on iodine intake, and that an isotope of iodine be used in calculating the weight of thyroid gland for dosimetry purposes."} {"id": "PMID:1272813", "title": "[Studies of hepatobiliary function with a scintillation camera and electronic data processing)].", "content": "The authors performed the sequential scintigraphy after intravenous application of 131I-BSP using the scintillation camera. During the first 60 minutes the pictures of the liver and of the mesogastrium were recorded in one-minute intervals on the digital magnetic tape. The following scintigrams were then recorded after 3 and 24 hours after the injection. Choosing the region of interest the authors noted the histograms above the liver and above the mesogastrium, evaluated then the proportion of impulse rate above the liver and mesogastrium in measured intervals and obtained using the digital computer the velocity coefficient of the radioactivity accumulation in the liver as liver chromoexcretive function parameter. The results were compared with the standard test of the 45-minutes retention of the BSP, with the analysis of the curve measured above the temporal region, with the clinical status as well as with the results of other auxiliary examination methods. According to the first experiences gained when examining 91 individuals the described method proves to be very useful.", "contents": "[Studies of hepatobiliary function with a scintillation camera and electronic data processing)]. The authors performed the sequential scintigraphy after intravenous application of 131I-BSP using the scintillation camera. During the first 60 minutes the pictures of the liver and of the mesogastrium were recorded in one-minute intervals on the digital magnetic tape. The following scintigrams were then recorded after 3 and 24 hours after the injection. Choosing the region of interest the authors noted the histograms above the liver and above the mesogastrium, evaluated then the proportion of impulse rate above the liver and mesogastrium in measured intervals and obtained using the digital computer the velocity coefficient of the radioactivity accumulation in the liver as liver chromoexcretive function parameter. The results were compared with the standard test of the 45-minutes retention of the BSP, with the analysis of the curve measured above the temporal region, with the clinical status as well as with the results of other auxiliary examination methods. According to the first experiences gained when examining 91 individuals the described method proves to be very useful."} {"id": "PMID:1272814", "title": "99mT-c-pyridoxylidene glutamate a radiopharmaceutical for the hepatobiliary system.", "content": "99MTc-pyridoxylidene glutamate is a good agent to visualize the hepatobiliary system. The method of preparation and quality control, and preliminary data on its behaviour in human controls is presented. In humans the gall bladder could be well seen in about 15--20 minutes after intravenous injection.", "contents": "99mT-c-pyridoxylidene glutamate a radiopharmaceutical for the hepatobiliary system. 99MTc-pyridoxylidene glutamate is a good agent to visualize the hepatobiliary system. The method of preparation and quality control, and preliminary data on its behaviour in human controls is presented. In humans the gall bladder could be well seen in about 15--20 minutes after intravenous injection."} {"id": "PMID:1272815", "title": "[Heart-blood-pool scintigraphy in dialyzed chronic uremic patients)].", "content": "The author have carried out scintigraphic measurements of the heart in order to diagnose the presence of an exudative pericarditis 50 times in 26 dialyzed uremic patients. Within the one year's observation 13 patients had an exudative pericarditis from the beginning on. In 8 cases a regression of the exudation could be observed. The examination has a low risk for the patient and is suitable to demonstrate clinically relevant pericardial liquid accumulation.", "contents": "[Heart-blood-pool scintigraphy in dialyzed chronic uremic patients)]. The author have carried out scintigraphic measurements of the heart in order to diagnose the presence of an exudative pericarditis 50 times in 26 dialyzed uremic patients. Within the one year's observation 13 patients had an exudative pericarditis from the beginning on. In 8 cases a regression of the exudation could be observed. The examination has a low risk for the patient and is suitable to demonstrate clinically relevant pericardial liquid accumulation."} {"id": "PMID:1272816", "title": "Calcium metabolism in children suffering from homozygous beta-thalassaemia after oral administration of 47Ca.", "content": "The study of calcium metabolism in ten thalassaemic children comperatively with controls after oral administration of 47Ca has shown diminished intestinal absorption. It is suggested that this finding is propably related in part with the pathogenesis of the osteoporosis in thalassaemia.", "contents": "Calcium metabolism in children suffering from homozygous beta-thalassaemia after oral administration of 47Ca. The study of calcium metabolism in ten thalassaemic children comperatively with controls after oral administration of 47Ca has shown diminished intestinal absorption. It is suggested that this finding is propably related in part with the pathogenesis of the osteoporosis in thalassaemia."} {"id": "PMID:1272817", "title": "Quality control and testing of 99mTc-macroaggregated albumin.", "content": "99mTc-labelled macroaggregated albumin particles prepared from a commercial \"kit\" have been tested in detail. With the introduction of the method of gel chromatography column scanning it became possible to make fast and simple quantitative measurements of the radiochemical purity. This was found to be the only reliable method for quantitative determination of non-aggregated 99mTc-labelled albumin. The measuring results of the kit in question have shown a labelling efficiency of about 97--99%. In addition to a few percent of 99m-Tc-pertechnetate less than 0.5% of disturbing radioactivity was found. The labelling was stable for at least 5--6 h. About 80% of the particles are in the size-range of 10--80 mum. A rough estimation of the number of particles in the solution resulted in 0.4-10(6) per mg of MAA. The dynamic studies of the lung uptake and the elimination of 99mTc-MAA in man resulted in a biological half-time in the lungs of about 1--2 h. The radiation absorbed dose to the lungs per mCi administered 99mTc-MAA was estimated to 0.1 rad. Less than 1% of the radioactivity was accumulated in liver, spleen or kidneys during the first 25 minutes after injection.", "contents": "Quality control and testing of 99mTc-macroaggregated albumin. 99mTc-labelled macroaggregated albumin particles prepared from a commercial \"kit\" have been tested in detail. With the introduction of the method of gel chromatography column scanning it became possible to make fast and simple quantitative measurements of the radiochemical purity. This was found to be the only reliable method for quantitative determination of non-aggregated 99mTc-labelled albumin. The measuring results of the kit in question have shown a labelling efficiency of about 97--99%. In addition to a few percent of 99m-Tc-pertechnetate less than 0.5% of disturbing radioactivity was found. The labelling was stable for at least 5--6 h. About 80% of the particles are in the size-range of 10--80 mum. A rough estimation of the number of particles in the solution resulted in 0.4-10(6) per mg of MAA. The dynamic studies of the lung uptake and the elimination of 99mTc-MAA in man resulted in a biological half-time in the lungs of about 1--2 h. The radiation absorbed dose to the lungs per mCi administered 99mTc-MAA was estimated to 0.1 rad. Less than 1% of the radioactivity was accumulated in liver, spleen or kidneys during the first 25 minutes after injection."} {"id": "PMID:1273007", "title": "[Biostability of plastic endotheses].", "content": "These is shown in this paper the literature review and author's studies on the in vitro and in vivo ageing changes in plastic endotheses under certain conditions. The changes occurring in endotheses exposed to no major mechanical loads were considered in particular. Polyamides, polyethylene derivatives, polyesters, polyurethanes and silicone rubbers were found to belong to the polymers unstable under biological conditions.olyesters, polyurethanes and silicone rubbers were found to belong to the polymers unstable under biological conditions.", "contents": "[Biostability of plastic endotheses]. These is shown in this paper the literature review and author's studies on the in vitro and in vivo ageing changes in plastic endotheses under certain conditions. The changes occurring in endotheses exposed to no major mechanical loads were considered in particular. Polyamides, polyethylene derivatives, polyesters, polyurethanes and silicone rubbers were found to belong to the polymers unstable under biological conditions.olyesters, polyurethanes and silicone rubbers were found to belong to the polymers unstable under biological conditions."} {"id": "PMID:1273008", "title": "[Spontaneous intrauterine rupture of contraceptive Lippes loop].", "content": "Basing of 2 clinical cases, the spontaneous intrauterine rupture of contraceptive Lippes loop has been discussed. The analysis of complications accompanying application of contraceptives of this type is presented.", "contents": "[Spontaneous intrauterine rupture of contraceptive Lippes loop]. Basing of 2 clinical cases, the spontaneous intrauterine rupture of contraceptive Lippes loop has been discussed. The analysis of complications accompanying application of contraceptives of this type is presented."} {"id": "PMID:1273009", "title": "[Disinfection of medical orthopedic articles made of polymer materials].", "content": "In traumatological hospitals the medical orthopedic articles made of polymer materials are contaminated by different microorganisms including pathogenic staphylococci, therefore they can serve as a factor of transmission of hospital-associated staphylococcal infections. Polymer materials used for medical orthopedic articles are not bactericidal. Mechanical cleaning with detergents does not provide sufficient elimination of microorganisms from orthopedic articles. This can be obtained by means of the treatment (immersion, wiping) with solutions of bactericidal preparations of various chemical orogin (chloramine, lithium hypochloride, chlorine, sulphochlorantine, hydrogen peroxide, peracetic acid, nitran). Medical orthopedic articles must be decontaminated before use. In the hospitals, disinfection of orthopedic articles should be performed at least once a day. Immersion of the articles made of porous materials into solutions of disinfectans with surface-active additives or into solutions of surface-active bactericides is a simple, readily available and effective method of treatment. Drawback of this method is that disinfectant solution partly remains in the pores and can be eliminated only by means of drying of the article in thermostate. Orthopedic articles of polyurethane foam can be decontaminated only by use of solutions of hydrogen peroxide and nirtan out of all the tested disinfectants. Medical orthopedic articles made of polymer materials have endured repeated treatment with disinfectant solutions without any change of their physical and mechanical properties. The usability of these articles did not deteriorate.", "contents": "[Disinfection of medical orthopedic articles made of polymer materials]. In traumatological hospitals the medical orthopedic articles made of polymer materials are contaminated by different microorganisms including pathogenic staphylococci, therefore they can serve as a factor of transmission of hospital-associated staphylococcal infections. Polymer materials used for medical orthopedic articles are not bactericidal. Mechanical cleaning with detergents does not provide sufficient elimination of microorganisms from orthopedic articles. This can be obtained by means of the treatment (immersion, wiping) with solutions of bactericidal preparations of various chemical orogin (chloramine, lithium hypochloride, chlorine, sulphochlorantine, hydrogen peroxide, peracetic acid, nitran). Medical orthopedic articles must be decontaminated before use. In the hospitals, disinfection of orthopedic articles should be performed at least once a day. Immersion of the articles made of porous materials into solutions of disinfectans with surface-active additives or into solutions of surface-active bactericides is a simple, readily available and effective method of treatment. Drawback of this method is that disinfectant solution partly remains in the pores and can be eliminated only by means of drying of the article in thermostate. Orthopedic articles of polyurethane foam can be decontaminated only by use of solutions of hydrogen peroxide and nirtan out of all the tested disinfectants. Medical orthopedic articles made of polymer materials have endured repeated treatment with disinfectant solutions without any change of their physical and mechanical properties. The usability of these articles did not deteriorate."} {"id": "PMID:1273010", "title": "[Ethylene oxide sterilization and disinfection of plastic articles].", "content": "The outline of progress in the use of ethylene oxide sterilization of thermolabile plastic articles is presented. The explosiveness, adsorption and toxicity of the ethylene oxide and the influence of humidity on its bactericidal effectivity are especially emphasized. The methods of checking-up sterilization processes are indicated.", "contents": "[Ethylene oxide sterilization and disinfection of plastic articles]. The outline of progress in the use of ethylene oxide sterilization of thermolabile plastic articles is presented. The explosiveness, adsorption and toxicity of the ethylene oxide and the influence of humidity on its bactericidal effectivity are especially emphasized. The methods of checking-up sterilization processes are indicated."} {"id": "PMID:1273011", "title": "[Morphology and histochemistry of tissues surrounding liquid and cured silicone rubber].", "content": "The process of encapsulation of SKTN liquid silicone rubber of 30-50 thousand molecular weight, and of SKTN compounds curing in the tissues was observed experimentally. The silicone implants were surrounded by mature connective tissue after 3.0-4.5 years. The method of silicone administration, whether by injection or by implantation of prefabricated solid prostheses, exerted no effect on the local tissue reaction.", "contents": "[Morphology and histochemistry of tissues surrounding liquid and cured silicone rubber]. The process of encapsulation of SKTN liquid silicone rubber of 30-50 thousand molecular weight, and of SKTN compounds curing in the tissues was observed experimentally. The silicone implants were surrounded by mature connective tissue after 3.0-4.5 years. The method of silicone administration, whether by injection or by implantation of prefabricated solid prostheses, exerted no effect on the local tissue reaction."} {"id": "PMID:1273032", "title": "A comparative study of talampicillin and ampicillin in general practice.", "content": "Talampicillin hydrochloride, the phthalidyl ester of ampicillin, when given in a dosage containing the equivalent of 125 mg of ampicillin four times daily for six days to general practice patients, has proved to be as effective, both clinically and bacteriologically, as 250 mg of ampicillin given four times daily for six days. Although the over-all incidence of side-effects was similar with both preparations, diarrhoea was significantly reduced in talampicillin-treated patients. Possible reasons for this are discussed. Talampicillin therefore offers certain advantages over ampicillin in producing effectiveness equivalent to that of ampicillin at a lower dosage level with a reduced incidence of diarrhoea.", "contents": "A comparative study of talampicillin and ampicillin in general practice. Talampicillin hydrochloride, the phthalidyl ester of ampicillin, when given in a dosage containing the equivalent of 125 mg of ampicillin four times daily for six days to general practice patients, has proved to be as effective, both clinically and bacteriologically, as 250 mg of ampicillin given four times daily for six days. Although the over-all incidence of side-effects was similar with both preparations, diarrhoea was significantly reduced in talampicillin-treated patients. Possible reasons for this are discussed. Talampicillin therefore offers certain advantages over ampicillin in producing effectiveness equivalent to that of ampicillin at a lower dosage level with a reduced incidence of diarrhoea."} {"id": "PMID:1273034", "title": "Rapid purification of a high molecular weight human brain protein by chromatography on controlled pore glass.", "content": "Controlled pore glass (CPG) chromatography was employed to simply (one pass through column) and rapidly (60 minutes) purify a human brain specific protein having a high molecular weight (approximately 250,000 mol. wt.) from a crude brain extract containing proteins of varying molecular weights. This method, either exactly as described herein or by adjusting the pore size of the CPG, should be adaptable to other purification problems.", "contents": "Rapid purification of a high molecular weight human brain protein by chromatography on controlled pore glass. Controlled pore glass (CPG) chromatography was employed to simply (one pass through column) and rapidly (60 minutes) purify a human brain specific protein having a high molecular weight (approximately 250,000 mol. wt.) from a crude brain extract containing proteins of varying molecular weights. This method, either exactly as described herein or by adjusting the pore size of the CPG, should be adaptable to other purification problems."} {"id": "PMID:1273036", "title": "A single column packing for the gas-liquid chromatographic separation of various biologically important compounds.", "content": "The use of a single, commercially available column packing, TabsorbR, is described for the g.l.c. separation of a large number of different compounds. The resolution of the homologous members of the following series of compounds was achieved: (1) saturated fatty acids (C1-C18), (2) normal aliphatic saturated dicarboxylic acids (C2-C14), (3) normal aliphatic saturated alcohols (C1-C24), (4) normal aliphatic saturated amines (C1-C12), (5) the common amino acids except arginine, histidine and cysteine, (6) aliphatic hydrocarbons (C10-C20) and (7) monosaccharides. It should be noted that twenty-two monosaccharides including three hexosamines and two anhydrohexoses, could be resolved as alditol acetates in a single run. In addition, galacturonic, glucuronic and iduronic acids could be separated from one another as their 1,4-lactones. The resolution achieved in these series of compounds was found to be consistent and highly reproducible. It is of further interest that certain isomers of the higher fatty acids and hydrocarbons with one double bond could also be separated from the normal and saturated compounds, respectively. The applicability of \"Tabsorb\" for the g.l.c. separation, although noted above to be considerably broad, is by far not yet exhausted. These procedures which form the basis for the quantitative determinations of the various compounds studied as demonstrated by analysis of glycopeptides for neutral hexoses and proteins for the amino acids, can readily be adapted to preparative methods. From the biochemical point of view \"Tabsorb\" is an extremely versatile column packing in that it can be used for the identification of many of the common building blocks of natural products.", "contents": "A single column packing for the gas-liquid chromatographic separation of various biologically important compounds. The use of a single, commercially available column packing, TabsorbR, is described for the g.l.c. separation of a large number of different compounds. The resolution of the homologous members of the following series of compounds was achieved: (1) saturated fatty acids (C1-C18), (2) normal aliphatic saturated dicarboxylic acids (C2-C14), (3) normal aliphatic saturated alcohols (C1-C24), (4) normal aliphatic saturated amines (C1-C12), (5) the common amino acids except arginine, histidine and cysteine, (6) aliphatic hydrocarbons (C10-C20) and (7) monosaccharides. It should be noted that twenty-two monosaccharides including three hexosamines and two anhydrohexoses, could be resolved as alditol acetates in a single run. In addition, galacturonic, glucuronic and iduronic acids could be separated from one another as their 1,4-lactones. The resolution achieved in these series of compounds was found to be consistent and highly reproducible. It is of further interest that certain isomers of the higher fatty acids and hydrocarbons with one double bond could also be separated from the normal and saturated compounds, respectively. The applicability of \"Tabsorb\" for the g.l.c. separation, although noted above to be considerably broad, is by far not yet exhausted. These procedures which form the basis for the quantitative determinations of the various compounds studied as demonstrated by analysis of glycopeptides for neutral hexoses and proteins for the amino acids, can readily be adapted to preparative methods. From the biochemical point of view \"Tabsorb\" is an extremely versatile column packing in that it can be used for the identification of many of the common building blocks of natural products."} {"id": "PMID:1273040", "title": "[Some aspects of evaluating the thyroid gland scanning image normally and in pathology].", "content": "The authors studied 1252 scannograms of 1170 patients. Plane image variants of the shape of normal, dystopic and maldeveloped thyroid gland were studied. Scannographic image of the structure of pathology of the organ and peculiarities of absorption and distribution of radioactive indicators (I131, Tc99m), depending on the histological picture of the pathological process and other factors stimulating or blocking its function are discussed. Practical significance of the method in clinical endocrinology is emphasized and sources of diagnostic errors possible in interpretation of the form and structure of the scannographic picture of the gland under normal and pathological conditions are elucidated.", "contents": "[Some aspects of evaluating the thyroid gland scanning image normally and in pathology]. The authors studied 1252 scannograms of 1170 patients. Plane image variants of the shape of normal, dystopic and maldeveloped thyroid gland were studied. Scannographic image of the structure of pathology of the organ and peculiarities of absorption and distribution of radioactive indicators (I131, Tc99m), depending on the histological picture of the pathological process and other factors stimulating or blocking its function are discussed. Practical significance of the method in clinical endocrinology is emphasized and sources of diagnostic errors possible in interpretation of the form and structure of the scannographic picture of the gland under normal and pathological conditions are elucidated."} {"id": "PMID:1273041", "title": "[Comparison of the nature of insulin secretion, determined by radioimmune and biological methods, normally and in diabetes mellitus].", "content": "The character of insulin secretion curves was studied under normal conditions and in diabetic patients during glucose tolerance test. Patients with diabetes mellitus were divided into the following groups: donors, patients with reduced glucose tolerance and with manifest diabetes. Insulin was determined in paralleled by 3 methods (biological ones and radioimmune one). An increase in immunoreactive insulin was seen in the group of patients with reduced glucose tolerance during the whole course of the test with a peak at the 30th minute and a simultaneous reduction and a sharp fall at the 60th minute of free insulin level. Apparently biologically less active forms of insulin and proinsulin are secreted which possess immunological properties and react well with antibodies to insulin.", "contents": "[Comparison of the nature of insulin secretion, determined by radioimmune and biological methods, normally and in diabetes mellitus]. The character of insulin secretion curves was studied under normal conditions and in diabetic patients during glucose tolerance test. Patients with diabetes mellitus were divided into the following groups: donors, patients with reduced glucose tolerance and with manifest diabetes. Insulin was determined in paralleled by 3 methods (biological ones and radioimmune one). An increase in immunoreactive insulin was seen in the group of patients with reduced glucose tolerance during the whole course of the test with a peak at the 30th minute and a simultaneous reduction and a sharp fall at the 60th minute of free insulin level. Apparently biologically less active forms of insulin and proinsulin are secreted which possess immunological properties and react well with antibodies to insulin."} {"id": "PMID:1273042", "title": "[Experience with the tegretol treatment of diabetes insipidus].", "content": "The use of tegretol in a 24-hour dose of 200-600 mg in 12 patients with diabetes incipidus led to the improvement of their general condition, lesser thirst, reduction of the 24-hour diuresis and increase of specific gravity of the urine. A positive effect of prescribing tegretol together with chlorpropamide was noted in a patient with diabetes mellitus and incipidus.", "contents": "[Experience with the tegretol treatment of diabetes insipidus]. The use of tegretol in a 24-hour dose of 200-600 mg in 12 patients with diabetes incipidus led to the improvement of their general condition, lesser thirst, reduction of the 24-hour diuresis and increase of specific gravity of the urine. A positive effect of prescribing tegretol together with chlorpropamide was noted in a patient with diabetes mellitus and incipidus."} {"id": "PMID:1273043", "title": "[Sex hormone reception in the human endometrium in normal and pathological pregnancy].", "content": "A study was made of reception of 17 beta-estradiol, progesterone, and testosterone in human endometrium during pregnancy. In the cytozol of the endometrium each of the sex steroids was bound by three different receptor components, two of which were represented by highly specific proteins. The maximal capacity of specific cytozol receptors to each of the sex steroids was measured in normal and pathological pregnancy; in the latter case the number of receptors to progesterone proved to be decreased. It is supposed that one of the specific binding components is necessary only under conditions of increased functional load upon the organ.", "contents": "[Sex hormone reception in the human endometrium in normal and pathological pregnancy]. A study was made of reception of 17 beta-estradiol, progesterone, and testosterone in human endometrium during pregnancy. In the cytozol of the endometrium each of the sex steroids was bound by three different receptor components, two of which were represented by highly specific proteins. The maximal capacity of specific cytozol receptors to each of the sex steroids was measured in normal and pathological pregnancy; in the latter case the number of receptors to progesterone proved to be decreased. It is supposed that one of the specific binding components is necessary only under conditions of increased functional load upon the organ."} {"id": "PMID:1273044", "title": "[State of the cardiovascular system in chromophobe adenoma of the hypophysis].", "content": "The detected changes in the cardiovascular activity, primarily in the state of hemodynamics in patients with chromophobic adenoma of the hypophysis indicated a possible phasic character of the course of this disease. A sharp fall in the contractile capacity of the myocardium in a number of patients was most probably caused by marked hormonal and metabolic shifts developing against the background of insufficiency of the adeno-hypophysis. On the basis of the data obtained a detailed study of the state of the organs of circulation is recommended in all the patients with chromophobic adenoma of the hypophysis, particularly during the preoperative preparation.", "contents": "[State of the cardiovascular system in chromophobe adenoma of the hypophysis]. The detected changes in the cardiovascular activity, primarily in the state of hemodynamics in patients with chromophobic adenoma of the hypophysis indicated a possible phasic character of the course of this disease. A sharp fall in the contractile capacity of the myocardium in a number of patients was most probably caused by marked hormonal and metabolic shifts developing against the background of insufficiency of the adeno-hypophysis. On the basis of the data obtained a detailed study of the state of the organs of circulation is recommended in all the patients with chromophobic adenoma of the hypophysis, particularly during the preoperative preparation."} {"id": "PMID:1273045", "title": "[State of the bone marrow hematopoiesis and peripheral blood in obesity].", "content": "Peripheral blood was studied before and after the treatment in 186 patients with various forms of adiposity; bone marrow was examined in 10 patients. The data obtained were compared with the STH level in the blood serum in the corresponding patients. The bone marrow of patients with adiposity displayed a reduction of myelokariocytes on account of mature neutrophils and normoblasts, a fall in reticulocyte and megakariocyte count and an increase in lymphocytes. Peripheral blood is characterized by reticulocytopenia, a reduction of leukocytes on account of granulocytes and an accelerated ESR. Possibly the detected shifts in myelogram and the peripheral blood were caused by the principal pathological process and the change of the somatotropic function of the adenohypophysis.", "contents": "[State of the bone marrow hematopoiesis and peripheral blood in obesity]. Peripheral blood was studied before and after the treatment in 186 patients with various forms of adiposity; bone marrow was examined in 10 patients. The data obtained were compared with the STH level in the blood serum in the corresponding patients. The bone marrow of patients with adiposity displayed a reduction of myelokariocytes on account of mature neutrophils and normoblasts, a fall in reticulocyte and megakariocyte count and an increase in lymphocytes. Peripheral blood is characterized by reticulocytopenia, a reduction of leukocytes on account of granulocytes and an accelerated ESR. Possibly the detected shifts in myelogram and the peripheral blood were caused by the principal pathological process and the change of the somatotropic function of the adenohypophysis."} {"id": "PMID:1273048", "title": "[Role of different regions of the hypothalamus in regulating the hypophyseal-adrenal cortex system in rats].", "content": "The effect of electrical stimulation of various structures of the medial hypothalamus on the corticosterone level in the peripheral blood was studied in rats with preliminarily destroyed individual areas of the hypothalamus. Injury of various structures of the medial hypothalamus led the first days after the operation to reduction of the response to the stimulation. Two-three weeks after destruction of the anterior and the middle portions of the hypothalamus reactivity of the hypophyseo-adrenocortical system was restored, although not always completely. Only in destruction of the premamillary nuclei there was no restoration of the reaction. A conclusion was drawn that the area of the posterior hypothalamus was of great necessity for functional regulation of the hypophysis-adrenal cortex system.", "contents": "[Role of different regions of the hypothalamus in regulating the hypophyseal-adrenal cortex system in rats]. The effect of electrical stimulation of various structures of the medial hypothalamus on the corticosterone level in the peripheral blood was studied in rats with preliminarily destroyed individual areas of the hypothalamus. Injury of various structures of the medial hypothalamus led the first days after the operation to reduction of the response to the stimulation. Two-three weeks after destruction of the anterior and the middle portions of the hypothalamus reactivity of the hypophyseo-adrenocortical system was restored, although not always completely. Only in destruction of the premamillary nuclei there was no restoration of the reaction. A conclusion was drawn that the area of the posterior hypothalamus was of great necessity for functional regulation of the hypophysis-adrenal cortex system."} {"id": "PMID:1273049", "title": "[Interrelationship of the pineal body with the hypothalamo-hypophyseal complex. II. The effect of melatonin on the incorporation of H3-leucine in the anterior and medial hypothalamic nuclei of pinealectomized blinded rats].", "content": "A study was made of the effect of low doses of melatonin on the H3-leucine incorporation into the supraoptic, paraventricular, ventro-medial, and arcuate nuclei of the hypothalamus. Sexually mature blinded pinealectomized female rats were used in these experiments. Melatonin administered in a dose of 10 mug at 11 a.m. for 9 days inhibited the biosynthetic potential of the mentioned hypothalamic nuclei enhanced by extirpation of the epiphysis. Administration of melatonin at 11 p.m. in the same doses produced no effect on leucine incorporation.", "contents": "[Interrelationship of the pineal body with the hypothalamo-hypophyseal complex. II. The effect of melatonin on the incorporation of H3-leucine in the anterior and medial hypothalamic nuclei of pinealectomized blinded rats]. A study was made of the effect of low doses of melatonin on the H3-leucine incorporation into the supraoptic, paraventricular, ventro-medial, and arcuate nuclei of the hypothalamus. Sexually mature blinded pinealectomized female rats were used in these experiments. Melatonin administered in a dose of 10 mug at 11 a.m. for 9 days inhibited the biosynthetic potential of the mentioned hypothalamic nuclei enhanced by extirpation of the epiphysis. Administration of melatonin at 11 p.m. in the same doses produced no effect on leucine incorporation."} {"id": "PMID:1273050", "title": "[Congenital disorders of the thyroid gland in experimental litters obtained from mothers subjected to immunization and the action of I-131].", "content": "I131 injected to rabbits immunized with homologous thyroid gland on the 19th-20th day of pregnancy led to congenital disturbances of the thyroid gland in the experimental litters in the I and II generations. The functional activity and the activity of proteolytic enzymes of the thyroid gland decreased by the 30th day of the postnatal development. There was revealed a distinct correlation between the content in the thyroid gland of the experimental litters of DIT + MIT and of organic forms--T3 + T4. During the first days after birth DIT + MIT content showed a sharp fall and increased by the 30th day; on the contrary, iodine binding into organic forms decreased with the progress of age. Histological examination of the thyroid glands in the experimental litters demonstrated lymphoid-plasmocytic infiltration, along with connective tissue proliferation, which led to a marked sclerosis and fibrosis of tissues, hypofunction. Beginning from the age of one month there was seen an extensive nodular proliferation, which possibly served as the beginning of parenchymatous goiter formation. The appearance of lymphoid-plasmocytic infiltration in the thyroid gland of the II generation is considered to be the result of congenital predisposition to the autoimmune thyroiditis inlaid in the memory cells and intensified during birth.", "contents": "[Congenital disorders of the thyroid gland in experimental litters obtained from mothers subjected to immunization and the action of I-131]. I131 injected to rabbits immunized with homologous thyroid gland on the 19th-20th day of pregnancy led to congenital disturbances of the thyroid gland in the experimental litters in the I and II generations. The functional activity and the activity of proteolytic enzymes of the thyroid gland decreased by the 30th day of the postnatal development. There was revealed a distinct correlation between the content in the thyroid gland of the experimental litters of DIT + MIT and of organic forms--T3 + T4. During the first days after birth DIT + MIT content showed a sharp fall and increased by the 30th day; on the contrary, iodine binding into organic forms decreased with the progress of age. Histological examination of the thyroid glands in the experimental litters demonstrated lymphoid-plasmocytic infiltration, along with connective tissue proliferation, which led to a marked sclerosis and fibrosis of tissues, hypofunction. Beginning from the age of one month there was seen an extensive nodular proliferation, which possibly served as the beginning of parenchymatous goiter formation. The appearance of lymphoid-plasmocytic infiltration in the thyroid gland of the II generation is considered to be the result of congenital predisposition to the autoimmune thyroiditis inlaid in the memory cells and intensified during birth."} {"id": "PMID:1273051", "title": "[Electrolyte metabolism in hypothyroidism].", "content": "Sodium, potassium, calcium, magnesium content was determined in the blood plasma, erythrocytes and the 24-hour urine. There was revealed an increased sodium content in erythrocytes, a fall of plasma potassium level, a reduction of urinary potassium excretion and of potassium-magnesium coefficient of the urine; a tendency to increase in the calcium and magnesium level was seen in erythrocytes. Only calcium content in erythrocytes became normal after the treatment.", "contents": "[Electrolyte metabolism in hypothyroidism]. Sodium, potassium, calcium, magnesium content was determined in the blood plasma, erythrocytes and the 24-hour urine. There was revealed an increased sodium content in erythrocytes, a fall of plasma potassium level, a reduction of urinary potassium excretion and of potassium-magnesium coefficient of the urine; a tendency to increase in the calcium and magnesium level was seen in erythrocytes. Only calcium content in erythrocytes became normal after the treatment."} {"id": "PMID:1273052", "title": "[Reaction of the animal adrenal cortex to the action of a strong, constant magnetic field and to a hypomagnetic environment].", "content": "Experiments were conducted on male albino rats; a study was made of the functional condition of the adrenal cortex following a single 30-minute (decapitation of the animals in 1, 8, 16, and 24 hours, and in 4, 8, 16, and 30 days) and repeated (for 30 minutes every day) prolonged (for 1 month) action of CMF (decapitation in 2, 4, 8, 16, and 30 days) and hypomagnetic field (for 8 and 30 days). Changes in the lipid content and in the alkaline phosphatase activity served as a morpho-histochemical criterion. A single brief CMF action proved to stimulate the adrenal function the first hours of the after-action; later the changes were oscillating in character. Prolonged repeated action of CMF depressed the functional activity of the adrenal cortex. Both in the first and in the second cases functional activity of the organism was almost completely restored by the end of the month, after the cessation of the CMF action. An 8-day stay of the animals in the hypomagnetic medium led to activation of the adrenal gland function, and a 30-day stay--to its reduction.", "contents": "[Reaction of the animal adrenal cortex to the action of a strong, constant magnetic field and to a hypomagnetic environment]. Experiments were conducted on male albino rats; a study was made of the functional condition of the adrenal cortex following a single 30-minute (decapitation of the animals in 1, 8, 16, and 24 hours, and in 4, 8, 16, and 30 days) and repeated (for 30 minutes every day) prolonged (for 1 month) action of CMF (decapitation in 2, 4, 8, 16, and 30 days) and hypomagnetic field (for 8 and 30 days). Changes in the lipid content and in the alkaline phosphatase activity served as a morpho-histochemical criterion. A single brief CMF action proved to stimulate the adrenal function the first hours of the after-action; later the changes were oscillating in character. Prolonged repeated action of CMF depressed the functional activity of the adrenal cortex. Both in the first and in the second cases functional activity of the organism was almost completely restored by the end of the month, after the cessation of the CMF action. An 8-day stay of the animals in the hypomagnetic medium led to activation of the adrenal gland function, and a 30-day stay--to its reduction."} {"id": "PMID:1273053", "title": "[Change in aldosterone secretion by the adrenals and in its urinary excretion in rats under the action of acid polysaccharides].", "content": "Repeated administration of chondroitin sulfate to rats in doses of 20 and 120 mg/kg/24 hours led to reduction in the level of urinary aldosterone excretion in rats. Carboxymethylcellulose and alginic acid displayed no inhibitory effect. Urinary aldosterone excretion decreased in rats 24 hours after a single administration of chondroitin sulfate; this effect persisted for the following 3-4 days. The maximal reduction of aldosterone excretion (by 50%) occurred on the 3rd and the 4th day after administration of the preparation. Intraperitoneal injection of chondroitin sulfate to rats diminished the rate of aldosterone secretion by the adrenal glands; as to corticosterone secretion--it remained unchanged.", "contents": "[Change in aldosterone secretion by the adrenals and in its urinary excretion in rats under the action of acid polysaccharides]. Repeated administration of chondroitin sulfate to rats in doses of 20 and 120 mg/kg/24 hours led to reduction in the level of urinary aldosterone excretion in rats. Carboxymethylcellulose and alginic acid displayed no inhibitory effect. Urinary aldosterone excretion decreased in rats 24 hours after a single administration of chondroitin sulfate; this effect persisted for the following 3-4 days. The maximal reduction of aldosterone excretion (by 50%) occurred on the 3rd and the 4th day after administration of the preparation. Intraperitoneal injection of chondroitin sulfate to rats diminished the rate of aldosterone secretion by the adrenal glands; as to corticosterone secretion--it remained unchanged."} {"id": "PMID:1273054", "title": "[Blood proteins, thiol group metabolism and testosterone content in prostatic dysfunction].", "content": "A study was made of the blood serum proteins, thiol groups, aldolase activity, testosterone content in rabbits under conditions of insufficiency of the prostate gland caused by its suturing. It was revealed that at the late postoperative periods there was an increase in the blood serum proteins of albumin fraction, and a reduction of the thiol group level (SH-free, masked and disulfide). Aldolase activity increased at the early periods and then sharply fell. The incretory function of the testes was disturbed.", "contents": "[Blood proteins, thiol group metabolism and testosterone content in prostatic dysfunction]. A study was made of the blood serum proteins, thiol groups, aldolase activity, testosterone content in rabbits under conditions of insufficiency of the prostate gland caused by its suturing. It was revealed that at the late postoperative periods there was an increase in the blood serum proteins of albumin fraction, and a reduction of the thiol group level (SH-free, masked and disulfide). Aldolase activity increased at the early periods and then sharply fell. The incretory function of the testes was disturbed."} {"id": "PMID:1273099", "title": "Physical therapy program for the pediatric cardiac surgical patient.", "content": "The management of pediatric cardiac surgery patients at the North Carolina Memorial Hospital is described. The physical therapy program includes education and treatment which is intended to 1) reduce surgical risk by decreasing preoperative pulmonary congestion, 2) reduce the incidence of postoperative pulmonary complications and length of hospitalization, and 3) improve patient and family understanding and cooperation. The program includes a self-instructional package presented by a children's puppet. The package prepares the patient for the events ahead, including the physical therapy program and prospectively frightening aspects of intensive care.", "contents": "Physical therapy program for the pediatric cardiac surgical patient. The management of pediatric cardiac surgery patients at the North Carolina Memorial Hospital is described. The physical therapy program includes education and treatment which is intended to 1) reduce surgical risk by decreasing preoperative pulmonary congestion, 2) reduce the incidence of postoperative pulmonary complications and length of hospitalization, and 3) improve patient and family understanding and cooperation. The program includes a self-instructional package presented by a children's puppet. The package prepares the patient for the events ahead, including the physical therapy program and prospectively frightening aspects of intensive care."} {"id": "PMID:1273100", "title": "Physical therapy management of patients through cross modality.", "content": "Cross modality is a method for channeling therapeutic services from various health disciplines (modalities) through a single therapist who provides direct treatment and care. A pilot project at the University of Michigan's Institute for the Study of Mental Retardation and Related Disabilities tested this method in three mental retardation institutions. The ward attendant was designated as the primary therapist. The project staff included a physical therapist, speech therapist, occupational therapist, and nutritionist who taught ward attendants selected evaluation and treatment procedures. In theory, cross modality broadens the role of the institutional physical therapist to include teaching, monitoring of physical therapy services, and consulting with an institutional cross modality team which includes therapists (physical, occupational, speech), a dietitian, nurse(s), supervisor(s), and ward attendants. In practice, the therapist's attitude toward cross modality and the receptiveness of the ward attendant determine, the success of cross modality in any setting.", "contents": "Physical therapy management of patients through cross modality. Cross modality is a method for channeling therapeutic services from various health disciplines (modalities) through a single therapist who provides direct treatment and care. A pilot project at the University of Michigan's Institute for the Study of Mental Retardation and Related Disabilities tested this method in three mental retardation institutions. The ward attendant was designated as the primary therapist. The project staff included a physical therapist, speech therapist, occupational therapist, and nutritionist who taught ward attendants selected evaluation and treatment procedures. In theory, cross modality broadens the role of the institutional physical therapist to include teaching, monitoring of physical therapy services, and consulting with an institutional cross modality team which includes therapists (physical, occupational, speech), a dietitian, nurse(s), supervisor(s), and ward attendants. In practice, the therapist's attitude toward cross modality and the receptiveness of the ward attendant determine, the success of cross modality in any setting."} {"id": "PMID:1273105", "title": "Perception of coarticulated lip rounding.", "content": "This study investigates the perceivability of coarticulated lip rounding in French. Nine utterances containing the clusters /kstr/, /rstr/, and /rskr/ followed by one of the vowels /i/, /y/, or /u/ in all possible combinations, were truncated at 4 different points before the vowel. Test items in each of the 4 groups therefore contained different amounts of information regarding the nature of the following vowel, due to coarticulatory influences of the vowel on the preceding consonants. Subjects were asked to predict the identity of the missing vowel. Results show that when segments up to and including at least half of the final consonant of the cluster are present, subjects correctly identify the missing vowel well above chance level. Several individuals were able to identify the vowel even when presented with shorter versions of the utterances. No significant difference in performance was found between French and English subjects, nor between subjects with and without phonetic training. Pereceivability of individual features of the missing vowel is discussed. It is concluded that coarticulatory effects due to lip rounding (as well as to horizontal place of articulation) provide perceivable information at a level significantly above chance, and that this information may be used by the perceptual mechanism as an aid in speech sound identification.", "contents": "Perception of coarticulated lip rounding. This study investigates the perceivability of coarticulated lip rounding in French. Nine utterances containing the clusters /kstr/, /rstr/, and /rskr/ followed by one of the vowels /i/, /y/, or /u/ in all possible combinations, were truncated at 4 different points before the vowel. Test items in each of the 4 groups therefore contained different amounts of information regarding the nature of the following vowel, due to coarticulatory influences of the vowel on the preceding consonants. Subjects were asked to predict the identity of the missing vowel. Results show that when segments up to and including at least half of the final consonant of the cluster are present, subjects correctly identify the missing vowel well above chance level. Several individuals were able to identify the vowel even when presented with shorter versions of the utterances. No significant difference in performance was found between French and English subjects, nor between subjects with and without phonetic training. Pereceivability of individual features of the missing vowel is discussed. It is concluded that coarticulatory effects due to lip rounding (as well as to horizontal place of articulation) provide perceivable information at a level significantly above chance, and that this information may be used by the perceptual mechanism as an aid in speech sound identification."} {"id": "PMID:1273124", "title": "An alternative operation for inverted nipple.", "content": "An operation to correct inverted nipples is described. Its main advantage is that reinversion of the nipple is prevented, because two \"dermal\" flaps not only increase the density of tissue underneath the nipple but also act as slings.", "contents": "An alternative operation for inverted nipple. An operation to correct inverted nipples is described. Its main advantage is that reinversion of the nipple is prevented, because two \"dermal\" flaps not only increase the density of tissue underneath the nipple but also act as slings."} {"id": "PMID:1273126", "title": "A method for reconstruction of the central slip of the extensor tendon of a finger.", "content": "Congenital absence of the proximal interphalangeal joint extensor mechanism was corrected by using the lateral band and attached intrinsics of an adjacent finger. This technique has worked well in 3 cases.", "contents": "A method for reconstruction of the central slip of the extensor tendon of a finger. Congenital absence of the proximal interphalangeal joint extensor mechanism was corrected by using the lateral band and attached intrinsics of an adjacent finger. This technique has worked well in 3 cases."} {"id": "PMID:1273127", "title": "Elastogenesis in healing wounds in bats.", "content": "Full-thickness square wounds were made in the webs of fruit bats. Elastin was laid down in the healing scars of these wounds in two forms--as single fibers under the regenerated epidermis, and as bundles of fine fibers taking their origin and orientation from the cut ends of the web elastin bundles. This process continued over a period of 6 months, during which time other components of the scar became reduced in amount. The arrangement of the new elastin in the scar tissue was thus a replica of that seen in the normal web. There are indications in this study that elastin imparts elasticity to the scar.", "contents": "Elastogenesis in healing wounds in bats. Full-thickness square wounds were made in the webs of fruit bats. Elastin was laid down in the healing scars of these wounds in two forms--as single fibers under the regenerated epidermis, and as bundles of fine fibers taking their origin and orientation from the cut ends of the web elastin bundles. This process continued over a period of 6 months, during which time other components of the scar became reduced in amount. The arrangement of the new elastin in the scar tissue was thus a replica of that seen in the normal web. There are indications in this study that elastin imparts elasticity to the scar."} {"id": "PMID:1273128", "title": "Cephalometric study of facial growth in children after combined pushback and pharyngeal flap operations.", "content": "Linear and angular cephalometric measurements of children who had had combined palatal pushbacks and superiorly-based pharyngeal flaps do not show later growth retardation of the face. There was an inherent tendency for children with overt clefts of the secondary palate, classic submucous clefts, or occult submucous clefts to demonstrate pre-operatively a narrow SNA and SNB--but the difference between these angles (ANB) was normal.", "contents": "Cephalometric study of facial growth in children after combined pushback and pharyngeal flap operations. Linear and angular cephalometric measurements of children who had had combined palatal pushbacks and superiorly-based pharyngeal flaps do not show later growth retardation of the face. There was an inherent tendency for children with overt clefts of the secondary palate, classic submucous clefts, or occult submucous clefts to demonstrate pre-operatively a narrow SNA and SNB--but the difference between these angles (ANB) was normal."} {"id": "PMID:1273141", "title": "Mammaplasty with curved incisions.", "content": "We present a modification of Pitanguy's technique of mammaplasty. Curved incisions are used and the breast tissue is resected on a horizontal plane. We have done this operation in 130 consecutive mammaplasties and have had no complications. The esthetic results have been good.", "contents": "Mammaplasty with curved incisions. We present a modification of Pitanguy's technique of mammaplasty. Curved incisions are used and the breast tissue is resected on a horizontal plane. We have done this operation in 130 consecutive mammaplasties and have had no complications. The esthetic results have been good."} {"id": "PMID:1273143", "title": "\"De-epithelization\" of the dermal pedicle in a reduction mammaplasty.", "content": "Eleven biopsies in 6 consecutive patients having reduction mammaplasties by a technique which uses a dermal pedicle have established that dermis does remain in the pedicle. The term \"de-epithelization\" is not correct and should be abandoned in this context.", "contents": "\"De-epithelization\" of the dermal pedicle in a reduction mammaplasty. Eleven biopsies in 6 consecutive patients having reduction mammaplasties by a technique which uses a dermal pedicle have established that dermis does remain in the pedicle. The term \"de-epithelization\" is not correct and should be abandoned in this context."} {"id": "PMID:1273144", "title": "Skin testing for prognosis or therapy formulation in cancer patients: caveat emptor.", "content": "Delayed cutaneous hypersensitivity to DNCB was assessed in 56 patients who had epidermoid intraoral carcinoma, prior to therapy. They were followed for 44 months, and their skin reactivity correlated well with both a small tumor size and a favorable clinical prognosis. In a significant number of cases, however, lack of reactivity did not indicate a fatal outcome. Therefore, we recommend caution in the use of any skin test data in formulating therapy. When cured cancer patients were skin-tested, there was no correlation between the state of the disease and their skin reactivity.", "contents": "Skin testing for prognosis or therapy formulation in cancer patients: caveat emptor. Delayed cutaneous hypersensitivity to DNCB was assessed in 56 patients who had epidermoid intraoral carcinoma, prior to therapy. They were followed for 44 months, and their skin reactivity correlated well with both a small tumor size and a favorable clinical prognosis. In a significant number of cases, however, lack of reactivity did not indicate a fatal outcome. Therefore, we recommend caution in the use of any skin test data in formulating therapy. When cured cancer patients were skin-tested, there was no correlation between the state of the disease and their skin reactivity."} {"id": "PMID:1273148", "title": "A new mastopexy operation for mild or moderate breast ptosis.", "content": "A new procedure for mastopexy, with or wtihout an augmentatiom mammaplasty, is presented. Its advantage is the minimal resultant scarring in the least conspicuous location.", "contents": "A new mastopexy operation for mild or moderate breast ptosis. A new procedure for mastopexy, with or wtihout an augmentatiom mammaplasty, is presented. Its advantage is the minimal resultant scarring in the least conspicuous location."} {"id": "PMID:1273149", "title": "Frontonasal tumors: their diagnosis and management.", "content": "Fifty-three patients with frontonasal tumors were seen in a 17 -year period. Of these patients, 33 were females (62 percent) and 50 were caucasians (94 percent). The correct diagnosis was made preoperatively in 87 percent of the cases. Eighty-five percent of the patients were children, and most of the lesions (83 percent) were developmental anomalies rather than true neoplasms. The most common lesions were dermoids (17), hemangiomas (16), and encephaloceles (9), but 13 different types of lesions were encountered. The treatment of all is surgical excision, and a cooperative effort by the neurosurgeon and the plastic surgeon is required in some cases.", "contents": "Frontonasal tumors: their diagnosis and management. Fifty-three patients with frontonasal tumors were seen in a 17 -year period. Of these patients, 33 were females (62 percent) and 50 were caucasians (94 percent). The correct diagnosis was made preoperatively in 87 percent of the cases. Eighty-five percent of the patients were children, and most of the lesions (83 percent) were developmental anomalies rather than true neoplasms. The most common lesions were dermoids (17), hemangiomas (16), and encephaloceles (9), but 13 different types of lesions were encountered. The treatment of all is surgical excision, and a cooperative effort by the neurosurgeon and the plastic surgeon is required in some cases."} {"id": "PMID:1273150", "title": "Correction of asymmetries of the breasts.", "content": "The problem of asymmetries of the breasts is discussed. The technical details of one operation for unilateral reduction are described.", "contents": "Correction of asymmetries of the breasts. The problem of asymmetries of the breasts is discussed. The technical details of one operation for unilateral reduction are described."} {"id": "PMID:1273151", "title": "Skin tension lines in the domestic pig.", "content": "The skin tension lines of the domestic pig have been mapped. With a 6mm punch biopsy, local relative skin forces can be determined. The influence of various factors (such as age, fat deposition, gascial attachments, and previous scarring) on the direction of the skin tension lines is discussed.", "contents": "Skin tension lines in the domestic pig. The skin tension lines of the domestic pig have been mapped. With a 6mm punch biopsy, local relative skin forces can be determined. The influence of various factors (such as age, fat deposition, gascial attachments, and previous scarring) on the direction of the skin tension lines is discussed."} {"id": "PMID:1273154", "title": "Hemangiopericytoma of the hand. Case report.", "content": "We present one case of hemangiopericytoma of the hand. This lesion's clinical resemblance to glomus tumor is stressed; only the histological report could confirm the diagnosis.", "contents": "Hemangiopericytoma of the hand. Case report. We present one case of hemangiopericytoma of the hand. This lesion's clinical resemblance to glomus tumor is stressed; only the histological report could confirm the diagnosis."} {"id": "PMID:1273155", "title": "Giant breast implant for unilateral aplasia. Case report.", "content": "The authors present a patient who had aplasia of the right breast associated with absence of the pectoralis muscles and a chest wall deformity. The insertion of combined breast-chest wall implants improved her appearance markedly.", "contents": "Giant breast implant for unilateral aplasia. Case report. The authors present a patient who had aplasia of the right breast associated with absence of the pectoralis muscles and a chest wall deformity. The insertion of combined breast-chest wall implants improved her appearance markedly."} {"id": "PMID:1273167", "title": "Psychoanalytic approaches to artistic creativity.", "content": "Study of data and findings from clinical and applied psychoanalysis suggests a number of common factors encountered with uncommon frequency and intensity in creativity. In this paper, early childhood experiences, sensorial perceptions, body feelings, loneliness, reactions to loss, and body imagery of several artists are discussed. Problems relating to body image in creativeness are explored.", "contents": "Psychoanalytic approaches to artistic creativity. Study of data and findings from clinical and applied psychoanalysis suggests a number of common factors encountered with uncommon frequency and intensity in creativity. In this paper, early childhood experiences, sensorial perceptions, body feelings, loneliness, reactions to loss, and body imagery of several artists are discussed. Problems relating to body image in creativeness are explored."} {"id": "PMID:1273168", "title": "Transference regression and real experience in the psychoanalytic process.", "content": "At the patient's level of reality testing and integration in the transference neurosis, the analyst serves as an effective parent who halpd the 'child' master various danger situations. This results in the patients relearning and development as the analyst provides new experiences for the regressive childhood components of the patient's personality. There is also a sequential or simultaneous cognitive element which is important in the ultimate development of mastery and is particularly useful in the process of working through. This cognitive element, however, cannot be effectively used until there have been repeated new and real experiences for the fixated and/or regressive components of the patient's personality.", "contents": "Transference regression and real experience in the psychoanalytic process. At the patient's level of reality testing and integration in the transference neurosis, the analyst serves as an effective parent who halpd the 'child' master various danger situations. This results in the patients relearning and development as the analyst provides new experiences for the regressive childhood components of the patient's personality. There is also a sequential or simultaneous cognitive element which is important in the ultimate development of mastery and is particularly useful in the process of working through. This cognitive element, however, cannot be effectively used until there have been repeated new and real experiences for the fixated and/or regressive components of the patient's personality."} {"id": "PMID:1273169", "title": "The influence of the person of the analyst on structural change: a case report.", "content": "This paper attempts to demonstrate how values and attitudes of the analyst are inevitably communicated through the interpretative process and how they lead to structural change. Details of the analysis of a woman with a defective feminine self-representation are presented. A transference fantasy of the analyst's wife led to a fantasied ideal object with subsequent identification and modification of structure.", "contents": "The influence of the person of the analyst on structural change: a case report. This paper attempts to demonstrate how values and attitudes of the analyst are inevitably communicated through the interpretative process and how they lead to structural change. Details of the analysis of a woman with a defective feminine self-representation are presented. A transference fantasy of the analyst's wife led to a fantasied ideal object with subsequent identification and modification of structure."} {"id": "PMID:1273170", "title": "The future of psychoanalysis and its institutes.", "content": "If the function of psychoanalytic training institutes is to train practitioners of psychoanalytic technique, it is unreasonable to expect institutes to offer effective training in research or other scholarly applications of psychoanalysis. But if one insists that the training of psychoanalysts should, at least in some instances, encompass more than the teaching of psychoanalytic therapy, the training institutes have been failing in their function to educate candidates for scholarly activities. Whether the structure of the independent training institutes can permit such broadened training is questioned. One solution is to move the educational function into the university setting.", "contents": "The future of psychoanalysis and its institutes. If the function of psychoanalytic training institutes is to train practitioners of psychoanalytic technique, it is unreasonable to expect institutes to offer effective training in research or other scholarly applications of psychoanalysis. But if one insists that the training of psychoanalysts should, at least in some instances, encompass more than the teaching of psychoanalytic therapy, the training institutes have been failing in their function to educate candidates for scholarly activities. Whether the structure of the independent training institutes can permit such broadened training is questioned. One solution is to move the educational function into the university setting."} {"id": "PMID:1273171", "title": "The psychoanalytic treatment center as a transference object.", "content": "Three Treatment Center cases are presented. They reveal resistances and technical difficulties having to do with a split in the transference-the analyst viewed as the depriving mother and the Institute viewed as the nurturant grandmother. Possible implications for the conduct of student analyses are described.", "contents": "The psychoanalytic treatment center as a transference object. Three Treatment Center cases are presented. They reveal resistances and technical difficulties having to do with a split in the transference-the analyst viewed as the depriving mother and the Institute viewed as the nurturant grandmother. Possible implications for the conduct of student analyses are described."} {"id": "PMID:1273207", "title": "Effects of alcohol on male sexual responding.", "content": "Sixteen adult males participated in a repeated measures design in which they served as their own control to determine the effects of various amounts of alcohol on: (1) their sexual arousal elicited by erotic motion-pictures, as measured by a penile transducer, (2) the ability to voluntarily inhibit their arousal to those same films in accordance with instructions, and (3) the ability to become voluntarily aroused in the absence of overt stimuli. The ingestion of a low (0.5 or 0.6 ml/kg) or a moderate (1.0 or 1.2 ml/kg) amount of alcohol resulted in a small, but significant, depression of mean sexual arousal, but other measures were not affected. However, the ingestion of a high (1.5 or 1.8 ml/kg) amount of alcohol resulted in every measure of evoked arousal being depressed by a comparatively large degree. The high level of alcohol also affected a very large decrease in sexual arousal when subjects were instructed to become sexually aroused in the absence of overt erotic stimuli. In contrast, none of the three amounts of alcohol caused a significant impairment in the ability of subjects to voluntarily inhibit their sexual arousal, even though most subjects experienced some deterioration in that ability after ingesting a moderate amount of alcohol. The actions of alcohol on sexual responses were not significantly correlated with its effects on a nonsexual matching task, were not related to subjective reports of how alcohol usually affects sexual behavior, and were generally not related to reported drinking history.", "contents": "Effects of alcohol on male sexual responding. Sixteen adult males participated in a repeated measures design in which they served as their own control to determine the effects of various amounts of alcohol on: (1) their sexual arousal elicited by erotic motion-pictures, as measured by a penile transducer, (2) the ability to voluntarily inhibit their arousal to those same films in accordance with instructions, and (3) the ability to become voluntarily aroused in the absence of overt stimuli. The ingestion of a low (0.5 or 0.6 ml/kg) or a moderate (1.0 or 1.2 ml/kg) amount of alcohol resulted in a small, but significant, depression of mean sexual arousal, but other measures were not affected. However, the ingestion of a high (1.5 or 1.8 ml/kg) amount of alcohol resulted in every measure of evoked arousal being depressed by a comparatively large degree. The high level of alcohol also affected a very large decrease in sexual arousal when subjects were instructed to become sexually aroused in the absence of overt erotic stimuli. In contrast, none of the three amounts of alcohol caused a significant impairment in the ability of subjects to voluntarily inhibit their sexual arousal, even though most subjects experienced some deterioration in that ability after ingesting a moderate amount of alcohol. The actions of alcohol on sexual responses were not significantly correlated with its effects on a nonsexual matching task, were not related to subjective reports of how alcohol usually affects sexual behavior, and were generally not related to reported drinking history."} {"id": "PMID:1273208", "title": "Selective neuroendocrine effects of low-dose haloperidol in normal adult men.", "content": "The neuroendocrine effects of haloperidol, usually reported as side effects of this drug when given in antipsychotic doses, have not been systematically investigated. In the present study five normal adult men were administered saline and two doses of of haloperidol (0.25 mg, 0.5 mg) intramuscularly in a double-blind randomized block design. The anterior pituitary hormones GH, LH, FSH, and PRL were measured in blood samples taken every 20 min for several hours thereafter. The low doses of haloperidol used have been shown by others to alter the human EEG; in our subjects these doses produced no objective or subjective clinical effects. There were no drug related changes in GH, LH, or FSH. PRL, however, showed a prompt, statistically significant, dose-related increase in plasma levels, with a return to baseline with 5 h. Haloperidol has strong dopamine-blocking effects, and the hypothalamic inhibitory mechanism for PRL release is believed to be dopamine-mediated. The results of this study suggest that haloperidol may have utility in low doses primarily for its hypothalamic neuroendocrine effects, and that dose-related PRL release may be a useful paradigm for comparing dopamine-blocking antipsychotic agents in humans.", "contents": "Selective neuroendocrine effects of low-dose haloperidol in normal adult men. The neuroendocrine effects of haloperidol, usually reported as side effects of this drug when given in antipsychotic doses, have not been systematically investigated. In the present study five normal adult men were administered saline and two doses of of haloperidol (0.25 mg, 0.5 mg) intramuscularly in a double-blind randomized block design. The anterior pituitary hormones GH, LH, FSH, and PRL were measured in blood samples taken every 20 min for several hours thereafter. The low doses of haloperidol used have been shown by others to alter the human EEG; in our subjects these doses produced no objective or subjective clinical effects. There were no drug related changes in GH, LH, or FSH. PRL, however, showed a prompt, statistically significant, dose-related increase in plasma levels, with a return to baseline with 5 h. Haloperidol has strong dopamine-blocking effects, and the hypothalamic inhibitory mechanism for PRL release is believed to be dopamine-mediated. The results of this study suggest that haloperidol may have utility in low doses primarily for its hypothalamic neuroendocrine effects, and that dose-related PRL release may be a useful paradigm for comparing dopamine-blocking antipsychotic agents in humans."} {"id": "PMID:1273209", "title": "Sensory, perceptual, motor and cognitive functioning and subjective reports following oral administration of delta9-tetrahydrocannabinol.", "content": "Three dose levels, 0.2, 0.4, and 0.6 mg/kg, of delta9-tetrahydrocannabinol (THC) and a placebo were orally administered to 10 frequent and 10 occasional marijuana users. Following ingestion of each dose and the placebo, objective tests selected from a battery of sensory and perceptual motor tests routinely used to evaluate cerebral dysfunction in hospitalized patients were administered. The influence of delta9-THC on proficiency and variability of performance was minimal. However, when individual test scores and variabilities were combined and converted to standard scores, allowing for analysis of overall performance, THC had a small but consistent detrimental effect on both proficiency and variability of performance. In contrast, THC exerted profound effects on the subjective experiences of the volunteers as assessed by the Subjective Drug Effects Questionnaire. Subjective changes in mood, feeling, perception and somatic sensations were reported by all subjects but were more pronounced in the occasional user group. It was proposed that the small impairment noted in objective test performance after ingestion of delta9-THC as contrasted to the large effects on subjective responses suggests that the principal effects of marijuana are on the autonomic nervous system rather than on higher cortical functions.", "contents": "Sensory, perceptual, motor and cognitive functioning and subjective reports following oral administration of delta9-tetrahydrocannabinol. Three dose levels, 0.2, 0.4, and 0.6 mg/kg, of delta9-tetrahydrocannabinol (THC) and a placebo were orally administered to 10 frequent and 10 occasional marijuana users. Following ingestion of each dose and the placebo, objective tests selected from a battery of sensory and perceptual motor tests routinely used to evaluate cerebral dysfunction in hospitalized patients were administered. The influence of delta9-THC on proficiency and variability of performance was minimal. However, when individual test scores and variabilities were combined and converted to standard scores, allowing for analysis of overall performance, THC had a small but consistent detrimental effect on both proficiency and variability of performance. In contrast, THC exerted profound effects on the subjective experiences of the volunteers as assessed by the Subjective Drug Effects Questionnaire. Subjective changes in mood, feeling, perception and somatic sensations were reported by all subjects but were more pronounced in the occasional user group. It was proposed that the small impairment noted in objective test performance after ingestion of delta9-THC as contrasted to the large effects on subjective responses suggests that the principal effects of marijuana are on the autonomic nervous system rather than on higher cortical functions."} {"id": "PMID:1273210", "title": "The effects of pre-exposure to scopolamine on subsequent drug state discrimination.", "content": "This experiment was done to test the prediction that preexposure to a drug state would increase the discriminability of that drug state when used as a cue in a discrimination task. Eight rats were pre-exposed to scopolamine for 20 days and 8 rats were given saline injections. The drug pre-exposed animals acquired a drug state discrimination more quickly than the controls. A difference was also found between the generalization gradients for each group with the pre-exposed group showing a steeper generalization gradient.", "contents": "The effects of pre-exposure to scopolamine on subsequent drug state discrimination. This experiment was done to test the prediction that preexposure to a drug state would increase the discriminability of that drug state when used as a cue in a discrimination task. Eight rats were pre-exposed to scopolamine for 20 days and 8 rats were given saline injections. The drug pre-exposed animals acquired a drug state discrimination more quickly than the controls. A difference was also found between the generalization gradients for each group with the pre-exposed group showing a steeper generalization gradient."} {"id": "PMID:1273211", "title": "Ethanol and isopropanol effects on schedule-controlled responding.", "content": "The effects of ethanol and isopropanol were studied on responding by pigeons under multiple fixed-ratio (FR), fixed-interval (FI) schedules of food presentation and under a fixed-interval (FI) schedule of food presentation where responding was decreased by punishment. The ethanol was rapidly absorbed into blood and decreased responding within 15 min after intubation to the opening of the proventriculus. Dose-effect determinations of the effects of ethanol showed that ethanol decreased responding in both the FR and FI components of the multiple schedules at similar doses, but there were increases in responding under an FR 100 schedule at lower doses. Isopropanol tended to decrease FR responding at doses that either increased FI responding or did not affect FI responding. Both ethanol and isopropanol (1 g/kg) produced effects on the local rates of responding within the FI which were rate-dependent in that they increased low rates while not affecting or actually decreasing the high rates of responding. Both ethanol and isopropanol increased punished responding if it was not severely suppressed by the punishment procedures.", "contents": "Ethanol and isopropanol effects on schedule-controlled responding. The effects of ethanol and isopropanol were studied on responding by pigeons under multiple fixed-ratio (FR), fixed-interval (FI) schedules of food presentation and under a fixed-interval (FI) schedule of food presentation where responding was decreased by punishment. The ethanol was rapidly absorbed into blood and decreased responding within 15 min after intubation to the opening of the proventriculus. Dose-effect determinations of the effects of ethanol showed that ethanol decreased responding in both the FR and FI components of the multiple schedules at similar doses, but there were increases in responding under an FR 100 schedule at lower doses. Isopropanol tended to decrease FR responding at doses that either increased FI responding or did not affect FI responding. Both ethanol and isopropanol (1 g/kg) produced effects on the local rates of responding within the FI which were rate-dependent in that they increased low rates while not affecting or actually decreasing the high rates of responding. Both ethanol and isopropanol increased punished responding if it was not severely suppressed by the punishment procedures."} {"id": "PMID:1273212", "title": "Effects of caffeine consumption on nicotine consumption.", "content": "Coffee-drinking cigarette smokers take in more nicotine when they ingest almost no caffeine than when they ingest an amount of caffeine ranging from 75 mg to 300 mg. They do not take in relatively less nicotine as the dose of caffeine increases from 75 mg to 300 mg. It seems, then, that something due to caffeine deficit is responsible for the effect. Heavier users of caffeine show this effect less strongly than do lighter users of caffeine. These results are discussed in terms of the discriminability of caffeine and nicotine deficits and the possible influence of differential tolerance to caffeine. The importance of evaluating caffeine consumption when studying nicotine use and the importance of considering the chronic level and use of these drugs when studying their effects on behavior is indicated.", "contents": "Effects of caffeine consumption on nicotine consumption. Coffee-drinking cigarette smokers take in more nicotine when they ingest almost no caffeine than when they ingest an amount of caffeine ranging from 75 mg to 300 mg. They do not take in relatively less nicotine as the dose of caffeine increases from 75 mg to 300 mg. It seems, then, that something due to caffeine deficit is responsible for the effect. Heavier users of caffeine show this effect less strongly than do lighter users of caffeine. These results are discussed in terms of the discriminability of caffeine and nicotine deficits and the possible influence of differential tolerance to caffeine. The importance of evaluating caffeine consumption when studying nicotine use and the importance of considering the chronic level and use of these drugs when studying their effects on behavior is indicated."} {"id": "PMID:1273213", "title": "Therapeutical efficacy of a combination of apomorphine with sulpiride or metoclopramide in Parkinsonism.", "content": "In healthy volunteers the emetic effect of apomorphine (5-10 mg, i.m.) was prevented by haloperidol (2 mg), metoclopramide (10 mg) and sulpiride (100 mg), injected intramuscularly. In parkinsonian patients, apomorphine (1 mg) given alone ameliorated the neurological symptoms (30% improvement in the disability score), but the improvement was accompanied by nausea, vomiting, sedation or sleepiness. Haloperidol (2 mg) prevented not only the emetic effect of apomorphine (10 mg), but also its therapeutic efficacy in parkinsonism. Indeed, the disability score was worsened by the drug combination in some patients. Moreover, after haloperidol, apomorphine produced deep sedation and sleep. By contrast, in parkinsonian patients pretreated with metoclopramide (10 mg) or sulpiride (100 mg), apomorphine (10 mg) markedly diminished tremor and rigidity and failed to produce nausea, vomiting and sleepiness.", "contents": "Therapeutical efficacy of a combination of apomorphine with sulpiride or metoclopramide in Parkinsonism. In healthy volunteers the emetic effect of apomorphine (5-10 mg, i.m.) was prevented by haloperidol (2 mg), metoclopramide (10 mg) and sulpiride (100 mg), injected intramuscularly. In parkinsonian patients, apomorphine (1 mg) given alone ameliorated the neurological symptoms (30% improvement in the disability score), but the improvement was accompanied by nausea, vomiting, sedation or sleepiness. Haloperidol (2 mg) prevented not only the emetic effect of apomorphine (10 mg), but also its therapeutic efficacy in parkinsonism. Indeed, the disability score was worsened by the drug combination in some patients. Moreover, after haloperidol, apomorphine produced deep sedation and sleep. By contrast, in parkinsonian patients pretreated with metoclopramide (10 mg) or sulpiride (100 mg), apomorphine (10 mg) markedly diminished tremor and rigidity and failed to produce nausea, vomiting and sleepiness."} {"id": "PMID:1273214", "title": "Critical flicker frequency (CFF) and psychotropic drugs in normal human subjects-a review.", "content": "This literature review presents summary methodological and statistical data on 33 studies in which critical flicker frequency (CFF) thresholds were used to evaluate the effects of acute oral doses of single psychotropic drugs in normal human subjects. In all, 96 drug-dose-study combinations are represented. CFF was found to be altered to a statistically significant degree (P is less than 0.05) in 51 (65%) of the 79 instances in which inferential statistical methods were used to evaluate the results. As expected, stimulants increased CFF while hypnotics decreased it. There is also a discussion of important methodological considerations in the design of psychopharmacological studies employing CFF. While many studies have shown CFF to be sensitive to the effects of psychotropic drugs, there have not always been adequate controls for extraneous factors (especially, set and suggestion, changes in pupillary diameter, and the presence of other commonly used drugs). Finally, consideration is given to the attempts to increase the sensitivity of the CFF test to drug effects.", "contents": "Critical flicker frequency (CFF) and psychotropic drugs in normal human subjects-a review. This literature review presents summary methodological and statistical data on 33 studies in which critical flicker frequency (CFF) thresholds were used to evaluate the effects of acute oral doses of single psychotropic drugs in normal human subjects. In all, 96 drug-dose-study combinations are represented. CFF was found to be altered to a statistically significant degree (P is less than 0.05) in 51 (65%) of the 79 instances in which inferential statistical methods were used to evaluate the results. As expected, stimulants increased CFF while hypnotics decreased it. There is also a discussion of important methodological considerations in the design of psychopharmacological studies employing CFF. While many studies have shown CFF to be sensitive to the effects of psychotropic drugs, there have not always been adequate controls for extraneous factors (especially, set and suggestion, changes in pupillary diameter, and the presence of other commonly used drugs). Finally, consideration is given to the attempts to increase the sensitivity of the CFF test to drug effects."} {"id": "PMID:1273215", "title": "Effect of doxepin on uptake and efflux of serotonin human blood patelets in vitro.", "content": "It is shown that the tricyclic antidepressant drug doxepin (comprising 15% of the cis- and 85% of the trans-isomer) is a moderately potent competitive inhibitor of serotonin uptake in human blood platelets in vitro, with an inhibitory constant Ki of about 2 X 10(-7) M. The inhibitory effect was 6 times stronger in an artificial, protein-free medium than in diluted plasma, corresponding to about 85% protein binding. The efflux of serotonin from platelets preloaded with 14C-serotonin was not affected by doxepin in concentrations up to 10(-6) M, but increased rapidly at concentrations above 10(-4) M.", "contents": "Effect of doxepin on uptake and efflux of serotonin human blood patelets in vitro. It is shown that the tricyclic antidepressant drug doxepin (comprising 15% of the cis- and 85% of the trans-isomer) is a moderately potent competitive inhibitor of serotonin uptake in human blood platelets in vitro, with an inhibitory constant Ki of about 2 X 10(-7) M. The inhibitory effect was 6 times stronger in an artificial, protein-free medium than in diluted plasma, corresponding to about 85% protein binding. The efflux of serotonin from platelets preloaded with 14C-serotonin was not affected by doxepin in concentrations up to 10(-6) M, but increased rapidly at concentrations above 10(-4) M."} {"id": "PMID:1273216", "title": "The interaction between prostaglandin E1 and delta 9-tetrahydrocannabinol on intestinal motility and on the abdominal constriction response in the mouse.", "content": "The interaction between delta9-tetrahydrocannabinol (THC) and PGE1 was studied using two pharmacological parameters-the rate of passage of a charcoal meal through mouse small intestine and the abdominal constriction response in the mouse. PGE1 administered intraperitoneally produced a dose-dependent decrease in intestinal motility, and this effect was antagonized by low (0.25 mg/kg) doses of THC and potentiated by higher doses of THC (1 mg/kg). Kinetic analysis suggested that the interaction was of a mixed but predominantly competitive type. PGF2alpha produced an increase in intestinal motility but this was not dose-dependent. THC antagonized the effect of PGF2alpha in a dose-dependent manner suggestive of a physiological antagonism. THC (0.25-2 mg/kg) antagonized the dose-dependent PGE1 abdominal constriction response in a fashion which suggested a mixed (though mainly competitive) antagonism. It would ssem, therefore, that on the two pharmacological parameters studied THC appears to be interacting with PGE1 at the same receptor site. Although the doses of THC used are within the range of those used in man, it is not implied that these results are necessarily implicated in the psychoactivity of the drug.", "contents": "The interaction between prostaglandin E1 and delta 9-tetrahydrocannabinol on intestinal motility and on the abdominal constriction response in the mouse. The interaction between delta9-tetrahydrocannabinol (THC) and PGE1 was studied using two pharmacological parameters-the rate of passage of a charcoal meal through mouse small intestine and the abdominal constriction response in the mouse. PGE1 administered intraperitoneally produced a dose-dependent decrease in intestinal motility, and this effect was antagonized by low (0.25 mg/kg) doses of THC and potentiated by higher doses of THC (1 mg/kg). Kinetic analysis suggested that the interaction was of a mixed but predominantly competitive type. PGF2alpha produced an increase in intestinal motility but this was not dose-dependent. THC antagonized the effect of PGF2alpha in a dose-dependent manner suggestive of a physiological antagonism. THC (0.25-2 mg/kg) antagonized the dose-dependent PGE1 abdominal constriction response in a fashion which suggested a mixed (though mainly competitive) antagonism. It would ssem, therefore, that on the two pharmacological parameters studied THC appears to be interacting with PGE1 at the same receptor site. Although the doses of THC used are within the range of those used in man, it is not implied that these results are necessarily implicated in the psychoactivity of the drug."} {"id": "PMID:1273217", "title": "Effects of dopamine receptor stimulants on locomotor activity of rats with electrolytic or 6-hydroxydopamine-induced lesions of the nucleus accumbens.", "content": "Ergometrine (8 mg/kg) injected intraperitoneally into normal rats had little effect on locomotor activity. In contrast, rats with selective 6-hydroxydopamine-induced lesions of dopamine terminals in the nucleus accumbens showed a strong stimulation of locomotor activity following injection of this dose or ergometrine. The dopamine analogue 2-amino-6-7-dihydroxy-1, 2, 3, 4-tetrahydronaphthalene (ADTN) (150 mug), caused strong and long lasting stimulation of locomotor activity when injected intracerebroventricularly into rats. The ADTN response was markedly reduced in rats with bilateral electrolytic lesions of the nucleus accumbens, but unchanged in rats with bilateral electrolytic lesions of the caudate nucleus. At a lower dose level (50 mug) ADTN, injected intracerebroventricularly, had little effect on the locomotor activity of normal or sham-operated rats. This dose of ADTN was, however, effective in causing locomotor stimulation of rats with bilateral 6-hydroxydopamine-induced lesions of the nucleus accumbens. These results support the view that the dopamine receptors in the nucleus accumbens are involved in the actions of locomotor stimulant drugs.", "contents": "Effects of dopamine receptor stimulants on locomotor activity of rats with electrolytic or 6-hydroxydopamine-induced lesions of the nucleus accumbens. Ergometrine (8 mg/kg) injected intraperitoneally into normal rats had little effect on locomotor activity. In contrast, rats with selective 6-hydroxydopamine-induced lesions of dopamine terminals in the nucleus accumbens showed a strong stimulation of locomotor activity following injection of this dose or ergometrine. The dopamine analogue 2-amino-6-7-dihydroxy-1, 2, 3, 4-tetrahydronaphthalene (ADTN) (150 mug), caused strong and long lasting stimulation of locomotor activity when injected intracerebroventricularly into rats. The ADTN response was markedly reduced in rats with bilateral electrolytic lesions of the nucleus accumbens, but unchanged in rats with bilateral electrolytic lesions of the caudate nucleus. At a lower dose level (50 mug) ADTN, injected intracerebroventricularly, had little effect on the locomotor activity of normal or sham-operated rats. This dose of ADTN was, however, effective in causing locomotor stimulation of rats with bilateral 6-hydroxydopamine-induced lesions of the nucleus accumbens. These results support the view that the dopamine receptors in the nucleus accumbens are involved in the actions of locomotor stimulant drugs."} {"id": "PMID:1273218", "title": "Abolition of the hippocampal theta activity and drug-learning dissociation.", "content": "Rats were trained to escape electric shock by running into one arm of a T-maze on 10-trial daily sessions with pentobarbital (10 mg/kg), and to the opposite arm of the maze on other sessions with saline, the drug and saline sessions being alternated. This drug-learning dissociation or state-dependent learning was achieved by rats with medial septal lesions, abolishing hippocampal theta activity, as efficiently as rats with cortical lesions and intact rats. The suggested relationship between drug-learning dissociation and the suppression of hippocampal theta waves, produced by the drug, was not evidenced.", "contents": "Abolition of the hippocampal theta activity and drug-learning dissociation. Rats were trained to escape electric shock by running into one arm of a T-maze on 10-trial daily sessions with pentobarbital (10 mg/kg), and to the opposite arm of the maze on other sessions with saline, the drug and saline sessions being alternated. This drug-learning dissociation or state-dependent learning was achieved by rats with medial septal lesions, abolishing hippocampal theta activity, as efficiently as rats with cortical lesions and intact rats. The suggested relationship between drug-learning dissociation and the suppression of hippocampal theta waves, produced by the drug, was not evidenced."} {"id": "PMID:1273219", "title": "Effects of low and moderate doses of chlorpromazine on discrimination learning in the rat.", "content": "The effects of chlorpromazine on the acquisition of a brightness discrimination with food reward were examined. Doses of 0.5, 1.0 or 2.0 mg/kg of CPZ as well as saline were administered intraperitoneally to 4 groups of 7 Sprague-Dawley rats, 1 h prior to testing. After a 3-week period of habituation and pre-training, rats were tested 20 trials a day, 7 days a week. No drug effect was found on the number of trials to reach a criterion of 18/20 successive correct responses, which required an average of 6.2 days of training. Precriterion latencies, however, showed an increase as a function of increasing dose level. Post-choice latencies were not affected, eliminating motor retardation as an explanation for the latency effect.", "contents": "Effects of low and moderate doses of chlorpromazine on discrimination learning in the rat. The effects of chlorpromazine on the acquisition of a brightness discrimination with food reward were examined. Doses of 0.5, 1.0 or 2.0 mg/kg of CPZ as well as saline were administered intraperitoneally to 4 groups of 7 Sprague-Dawley rats, 1 h prior to testing. After a 3-week period of habituation and pre-training, rats were tested 20 trials a day, 7 days a week. No drug effect was found on the number of trials to reach a criterion of 18/20 successive correct responses, which required an average of 6.2 days of training. Precriterion latencies, however, showed an increase as a function of increasing dose level. Post-choice latencies were not affected, eliminating motor retardation as an explanation for the latency effect."} {"id": "PMID:1273220", "title": "Residual effects of hypnotic drugs: evidence for individual differences on vigilance.", "content": "Twelve healthy volunteers were given butobarbitone 100 and 200 mg, nitrazepam 5 and 10 mg and 2 lactose dummy treatments, at 23.00 hours at weekly intervals over 6 weeks according to a balanced design and using double blind conditions. Performance was studied between 09.00 hours and 17.00 hours the following day. Significant (P is less than 0.05) impairment of tapping rate and digit symbol substitution occurred. No significant differences occurred between performance after active drug and dummy in auditory vigilance, and subjective effects. Examination of individual differences in the response of subjects to the 4 hypnotic drug treatments, compared with their responses after dummy, indicated that subjects could be divided into two groups. One group consistently rated themselved as more alert after hypnotics and their vigilance performance improved. The other group consistently were more drowsy after hypnotics and their performance was impaired. It is suggested that the improvement in the first group resulted from improved sleep quality sufficient to counteract the residual effect of the hypnotic, whereas the second group merely showed the residual effects of the drugs.", "contents": "Residual effects of hypnotic drugs: evidence for individual differences on vigilance. Twelve healthy volunteers were given butobarbitone 100 and 200 mg, nitrazepam 5 and 10 mg and 2 lactose dummy treatments, at 23.00 hours at weekly intervals over 6 weeks according to a balanced design and using double blind conditions. Performance was studied between 09.00 hours and 17.00 hours the following day. Significant (P is less than 0.05) impairment of tapping rate and digit symbol substitution occurred. No significant differences occurred between performance after active drug and dummy in auditory vigilance, and subjective effects. Examination of individual differences in the response of subjects to the 4 hypnotic drug treatments, compared with their responses after dummy, indicated that subjects could be divided into two groups. One group consistently rated themselved as more alert after hypnotics and their vigilance performance improved. The other group consistently were more drowsy after hypnotics and their performance was impaired. It is suggested that the improvement in the first group resulted from improved sleep quality sufficient to counteract the residual effect of the hypnotic, whereas the second group merely showed the residual effects of the drugs."} {"id": "PMID:1273236", "title": "Limbic system-adrenal cortex regulation in depression and schizophrenia.", "content": "Hypothalamo-pituitary-adrenal [HPA] activation and abnormal HPA regulatory mechanisms have been observed in depressed patients. Depressed and schizophrenic patients were studied to determine whether the HPA disturbances in depression are specific to this psychiatric illness or are mediated by nonspecific breakdown of psychological defense mechanisms. Despite the presence of severe ego defense breakdown and considerable secondary depressive symptomatology, the schizophrenic patients had normal HPA function. The depressed patients had elevated urine free cortisol excretion, high CSF cortisol levels, and did not show normal HPA suppression in response to dexamethasone. Within the depressed group significant correlations of HPA parameters were obtained with somatic features but not with ego breakdown features. After recovery depressed patients had more normal HPA function. The results indicate that HPA dysfunction can occur in association with primary depressive illness, that a psychoendocrine distinction can be made between primary depressive illness and secondary depressive symptomatology, and that psychological defense breakdown is not related to these neuroendocrine observations. Attention is drawn to the utility of urinary free cortisol measurement as a valuable index of HPA activation in psychoendocrine studies.", "contents": "Limbic system-adrenal cortex regulation in depression and schizophrenia. Hypothalamo-pituitary-adrenal [HPA] activation and abnormal HPA regulatory mechanisms have been observed in depressed patients. Depressed and schizophrenic patients were studied to determine whether the HPA disturbances in depression are specific to this psychiatric illness or are mediated by nonspecific breakdown of psychological defense mechanisms. Despite the presence of severe ego defense breakdown and considerable secondary depressive symptomatology, the schizophrenic patients had normal HPA function. The depressed patients had elevated urine free cortisol excretion, high CSF cortisol levels, and did not show normal HPA suppression in response to dexamethasone. Within the depressed group significant correlations of HPA parameters were obtained with somatic features but not with ego breakdown features. After recovery depressed patients had more normal HPA function. The results indicate that HPA dysfunction can occur in association with primary depressive illness, that a psychoendocrine distinction can be made between primary depressive illness and secondary depressive symptomatology, and that psychological defense breakdown is not related to these neuroendocrine observations. Attention is drawn to the utility of urinary free cortisol measurement as a valuable index of HPA activation in psychoendocrine studies."} {"id": "PMID:1273237", "title": "Visceral learning in asthma.", "content": "The hypothesis of visceral learning has opened a new avenue in the search for a pathway between psychosocial stimuli and physiological changes. To apply this approach to asthma required a technique for the measurement of the airways' patency, which could be interfaced with the strategy of visceral learning. The method of forced oscillations was shown to correlate highly with whole body plethysmography. The rapid output of the instrument was used on line to control a visual reinforcement signal. Forty-six mild asthmatics, blind to the effect sought in order to minimize the role of suggestion, were tested in a series of evolving experiments. In the first series, two groups of subjects (N=15,13) were able, with this sensory feedback, to decrease (p less than 0.01) their total respiratory resistance; subsequently a smaller group of subjects (N=5), who received reinforcement signals unrelated to the state of their airways, showed no such change. Similar results were obtained in the second series of tests; in A-B-B-A order, the subjects (N=13) received either contingent or noncontingent reinforcement; furthermore, the reinforcement was available only if their lung volume was within the range observed during baseline.", "contents": "Visceral learning in asthma. The hypothesis of visceral learning has opened a new avenue in the search for a pathway between psychosocial stimuli and physiological changes. To apply this approach to asthma required a technique for the measurement of the airways' patency, which could be interfaced with the strategy of visceral learning. The method of forced oscillations was shown to correlate highly with whole body plethysmography. The rapid output of the instrument was used on line to control a visual reinforcement signal. Forty-six mild asthmatics, blind to the effect sought in order to minimize the role of suggestion, were tested in a series of evolving experiments. In the first series, two groups of subjects (N=15,13) were able, with this sensory feedback, to decrease (p less than 0.01) their total respiratory resistance; subsequently a smaller group of subjects (N=5), who received reinforcement signals unrelated to the state of their airways, showed no such change. Similar results were obtained in the second series of tests; in A-B-B-A order, the subjects (N=13) received either contingent or noncontingent reinforcement; furthermore, the reinforcement was available only if their lung volume was within the range observed during baseline."} {"id": "PMID:1273238", "title": "Emotional labeling and overeating in obese and normal weight individuals.", "content": "It was hypothesized that obese individuals respond to unlabeled high arousal by overeating, while no such response was predicted for labeled high arousal states. Obese and normal weight subjects were led to believe that they were hearing their own heart beat, and that it was either fast or slow. A label for this heart rate either was or was not provided, and subjects' eating behavior was measured unobtrusively. The results supported these hypotheses: aroused obese subjects ate more when they could not identify the cause of their arousal than when a label was known. When obese subjects were calm, the presence or absence of a label did not affect their eating. Furthermore, obese subjects showed significant affect reduction following eating. Normal weight subjects were not affected by the presence or absence of an arousal label. Instead, they ate more when they called themselves calm than when anxious, and more when hungry than when full.", "contents": "Emotional labeling and overeating in obese and normal weight individuals. It was hypothesized that obese individuals respond to unlabeled high arousal by overeating, while no such response was predicted for labeled high arousal states. Obese and normal weight subjects were led to believe that they were hearing their own heart beat, and that it was either fast or slow. A label for this heart rate either was or was not provided, and subjects' eating behavior was measured unobtrusively. The results supported these hypotheses: aroused obese subjects ate more when they could not identify the cause of their arousal than when a label was known. When obese subjects were calm, the presence or absence of a label did not affect their eating. Furthermore, obese subjects showed significant affect reduction following eating. Normal weight subjects were not affected by the presence or absence of an arousal label. Instead, they ate more when they called themselves calm than when anxious, and more when hungry than when full."} {"id": "PMID:1273239", "title": "Signal detection theory and the psychophysics of pain: an introduction and review.", "content": "A brief explanation of signal detection theory is presented, followed by a review of the literature in which differences in pain report were analyzed to determine if changes were in sensitivity (physiological processes) or in response bias (a subject's willingness to report that a signal occurred). Three kinds of studies are reviewed: modification, procedural, and comparative and normative. The advantages of using a signal detection approach in pain research are emphasized. It is concluded that experimenters applying signal detection analysis to pain research should give greater consideration to methodological procedures and be cognizant of all possibilities for shifts in sensitivity (d)'.", "contents": "Signal detection theory and the psychophysics of pain: an introduction and review. A brief explanation of signal detection theory is presented, followed by a review of the literature in which differences in pain report were analyzed to determine if changes were in sensitivity (physiological processes) or in response bias (a subject's willingness to report that a signal occurred). Three kinds of studies are reviewed: modification, procedural, and comparative and normative. The advantages of using a signal detection approach in pain research are emphasized. It is concluded that experimenters applying signal detection analysis to pain research should give greater consideration to methodological procedures and be cognizant of all possibilities for shifts in sensitivity (d)'."} {"id": "PMID:1273240", "title": "Intravenous l-DOPA plus carbidopa in depressed patients: average evoked response, learning, and behavioral changes.", "content": "The peripheral decarboxylase inhibitor carbidopa (L-alphamethyl-dopa-hydrazine) allowed safe intravenous administration of L-DOPA in amounts sufficient to alter cortical average evoked response (AER) and learning function in 13 depressed patients. The apparently rapid conversion of L-DOPA to dopamine, as reported from studies in animals, is consistent with the 20-30 min onset of effects seen in our study. Unipolar and bipolar depressed patients responded differently to the alterations in brain biogenic amines and also to the nonspecific stress of the experiment. Intravenous L-DOPA given acutely had effects on the AER that were similar to those documented with oral dopa given chronically--an augmentation of amplitude--intensity slopes in unipolar patients and a relative reduction of slopes in bipolar patients. In contrast, intravenous L-DOPA did not enhance verbal learning as did chronic oral treatment, but rather was associated with reduced learning compared with placebo infusions. Different neurochemical changes following L-DOPA given in single intravenous doses may be responsible for the different learning and behavioral changes form those found previously with oral dopa administered chronically.", "contents": "Intravenous l-DOPA plus carbidopa in depressed patients: average evoked response, learning, and behavioral changes. The peripheral decarboxylase inhibitor carbidopa (L-alphamethyl-dopa-hydrazine) allowed safe intravenous administration of L-DOPA in amounts sufficient to alter cortical average evoked response (AER) and learning function in 13 depressed patients. The apparently rapid conversion of L-DOPA to dopamine, as reported from studies in animals, is consistent with the 20-30 min onset of effects seen in our study. Unipolar and bipolar depressed patients responded differently to the alterations in brain biogenic amines and also to the nonspecific stress of the experiment. Intravenous L-DOPA given acutely had effects on the AER that were similar to those documented with oral dopa given chronically--an augmentation of amplitude--intensity slopes in unipolar patients and a relative reduction of slopes in bipolar patients. In contrast, intravenous L-DOPA did not enhance verbal learning as did chronic oral treatment, but rather was associated with reduced learning compared with placebo infusions. Different neurochemical changes following L-DOPA given in single intravenous doses may be responsible for the different learning and behavioral changes form those found previously with oral dopa administered chronically."} {"id": "PMID:1273294", "title": "[Radionuclid szintigraphy of spleen alterations (author's transl)].", "content": "Selective or systemic imaging of the spleen by visualization of the reticulo-endothelial system together with the liver represents a non-invasive, innocuous examination. This study is indicated in diagnostically unclear diseases of the left upper abdomen with reference to splenic lesions. Spleen scan is able to demonstrate splenic enlargement which is not detectable in 70% of clinically examined patients. Suspicion for rupture or hematoma of the spleen with imminent delayed rupture represents an important up to now neglected indication for scanning. It should be performed prior to angiography. In liver cirrhosis, combination of liver and spleen scan gives important information about splenic size and radiopharmaceutical uptake. Splenic infarcts, tumors, cysts, and abscess may be recognized by spleen scan in different projection.", "contents": "[Radionuclid szintigraphy of spleen alterations (author's transl)]. Selective or systemic imaging of the spleen by visualization of the reticulo-endothelial system together with the liver represents a non-invasive, innocuous examination. This study is indicated in diagnostically unclear diseases of the left upper abdomen with reference to splenic lesions. Spleen scan is able to demonstrate splenic enlargement which is not detectable in 70% of clinically examined patients. Suspicion for rupture or hematoma of the spleen with imminent delayed rupture represents an important up to now neglected indication for scanning. It should be performed prior to angiography. In liver cirrhosis, combination of liver and spleen scan gives important information about splenic size and radiopharmaceutical uptake. Splenic infarcts, tumors, cysts, and abscess may be recognized by spleen scan in different projection."} {"id": "PMID:1273295", "title": "[Determination of spleen size by roentgenographic and nuclear medicine methods (author's transl)].", "content": "Knowing the splenic size is important in many medical diseases. This paper describes methods how to measure the size of the spleen by palpation, scan and a roentgenogram with soft tissue technique. In 486 normals medium splenic length was 12,8 +/- 1,9 cm measured roentgenographically. In 60 patients with splenomegaly the correlation coefficient between roentgenologically determined size and scintigraphically measured splenic length was 0,89, between radiologically determined size and estimated splenic weight by scan was 0.69. Nuclear medicine methods are important for exact evaluation of the size of the spleen, roentgenography is adequate in screening and control examinations.", "contents": "[Determination of spleen size by roentgenographic and nuclear medicine methods (author's transl)]. Knowing the splenic size is important in many medical diseases. This paper describes methods how to measure the size of the spleen by palpation, scan and a roentgenogram with soft tissue technique. In 486 normals medium splenic length was 12,8 +/- 1,9 cm measured roentgenographically. In 60 patients with splenomegaly the correlation coefficient between roentgenologically determined size and scintigraphically measured splenic length was 0,89, between radiologically determined size and estimated splenic weight by scan was 0.69. Nuclear medicine methods are important for exact evaluation of the size of the spleen, roentgenography is adequate in screening and control examinations."} {"id": "PMID:1273296", "title": "[False diagnosis of a splenic cyst. A report about arteriography in cystic lesions of the spleen (author's transl)].", "content": "A false diagnosis of splenic echinococcal cyst is reported. Angiographic criteria of this misleading lesion are compared with those of three cases with splenic cysts (two were confirmed surgically). Depending on the size of the cyst, spreading and dislocation of branches of splenic arteries as well as definitsmothly outlined parenchymal defects become visible. Surrounding parenchyma may be partially compressed. Calcifications of the cystic wall do not allow differentiation between primary and parasitic cysts. The Casoni test alone is not sufficient as a primary diagnostic tool as it is false positive often. Additional complement binding test for echinococcus is recommended.", "contents": "[False diagnosis of a splenic cyst. A report about arteriography in cystic lesions of the spleen (author's transl)]. A false diagnosis of splenic echinococcal cyst is reported. Angiographic criteria of this misleading lesion are compared with those of three cases with splenic cysts (two were confirmed surgically). Depending on the size of the cyst, spreading and dislocation of branches of splenic arteries as well as definitsmothly outlined parenchymal defects become visible. Surrounding parenchyma may be partially compressed. Calcifications of the cystic wall do not allow differentiation between primary and parasitic cysts. The Casoni test alone is not sufficient as a primary diagnostic tool as it is false positive often. Additional complement binding test for echinococcus is recommended."} {"id": "PMID:1273297", "title": "[Roentgenologic diagnosis of splenic trauma (author's transl)].", "content": "Description of radiologic criteria in splenic trauma. Abdominal plain film: Enlarged shadow of the spleen with blurred margins; elevation - or rupture - of the left diaphragm; homogenous radiodensity in the left hypochondriac region; fractures of ribs or transverse process. Angiography is indicated in doubtful cases to clarify the following lesions: contusion, sub-or extracapsular hematoma, rupture and fragmentation. Possible diagnostic errors in arteriography (63 examined cases) are discussed.", "contents": "[Roentgenologic diagnosis of splenic trauma (author's transl)]. Description of radiologic criteria in splenic trauma. Abdominal plain film: Enlarged shadow of the spleen with blurred margins; elevation - or rupture - of the left diaphragm; homogenous radiodensity in the left hypochondriac region; fractures of ribs or transverse process. Angiography is indicated in doubtful cases to clarify the following lesions: contusion, sub-or extracapsular hematoma, rupture and fragmentation. Possible diagnostic errors in arteriography (63 examined cases) are discussed."} {"id": "PMID:1273298", "title": "[Delayed rupture of a metastatic-spleen following coeliacography (author's transl)].", "content": "A 49-year-old female patient died 7 days after coeliacography due to delayed rupture of the spleen. Apparently banal events are able to cause rupture of the spleen if metastatic or other pathological alterations are present. There is a brief discussion whether or not coeliacography could induce rupture of the spleen.", "contents": "[Delayed rupture of a metastatic-spleen following coeliacography (author's transl)]. A 49-year-old female patient died 7 days after coeliacography due to delayed rupture of the spleen. Apparently banal events are able to cause rupture of the spleen if metastatic or other pathological alterations are present. There is a brief discussion whether or not coeliacography could induce rupture of the spleen."} {"id": "PMID:1273299", "title": "[Inflammatory renal pseudotumors (author's transl)].", "content": "Inflammatory renal pseudotumors represent a not uncommon finding and frequently pose a difficult differential diagnosis. The importance of a thoroughful radiological evaluation with special reference to angiography is stressed.", "contents": "[Inflammatory renal pseudotumors (author's transl)]. Inflammatory renal pseudotumors represent a not uncommon finding and frequently pose a difficult differential diagnosis. The importance of a thoroughful radiological evaluation with special reference to angiography is stressed."} {"id": "PMID:1273300", "title": "[Congenital pseudotumors of the kidney (author's transl)].", "content": "Congenital pseudotumors of the kidney represent a relatively common urographic finding. Their pathological urographic, and angiographic characteristics are discussed. As a rule a definitive angiographic diagnosis of these benigne lesions is possible and chirurgical exploration is therefore rarly indicated.", "contents": "[Congenital pseudotumors of the kidney (author's transl)]. Congenital pseudotumors of the kidney represent a relatively common urographic finding. Their pathological urographic, and angiographic characteristics are discussed. As a rule a definitive angiographic diagnosis of these benigne lesions is possible and chirurgical exploration is therefore rarly indicated."} {"id": "PMID:1273301", "title": "[The individual limit of normal spleen size in routine x-ray film (author's transl)].", "content": "The evaluation of spleen length from routine x-ray films of the left epigastrium of 97 healthy patients suggested a close correlation to the height of the 12th thoracic and the first three lumbar vertebral bodies. The normal ratio of spleen length to the vertebral height Th 12- L 3 is 0,82 +/- 0,09, two standard deviations are represented by ratios from 0,64 to 1,0. Spleen length over vertebral height Th 12 -L 3 indicates pathologic enlargment of the spleen. 54 patients with diseases which may cause splenomegaly showed spleen lengths mostly over the heights Th 12 - L 3.", "contents": "[The individual limit of normal spleen size in routine x-ray film (author's transl)]. The evaluation of spleen length from routine x-ray films of the left epigastrium of 97 healthy patients suggested a close correlation to the height of the 12th thoracic and the first three lumbar vertebral bodies. The normal ratio of spleen length to the vertebral height Th 12- L 3 is 0,82 +/- 0,09, two standard deviations are represented by ratios from 0,64 to 1,0. Spleen length over vertebral height Th 12 -L 3 indicates pathologic enlargment of the spleen. 54 patients with diseases which may cause splenomegaly showed spleen lengths mostly over the heights Th 12 - L 3."} {"id": "PMID:1273302", "title": "[Current status of preoperative localization in primary hyperparathyroidism (author's transl)].", "content": "Since Seldinger demonstrated in 1953 parathyroid adenomas by arteriography, numerous localizing procedures have been advocated. Based on our experience with selective venous sampling for measurement of parathyroid hormone by radioimmunoassay, selective arteriography, pneumomediastinography and scanning with 75Se-selenomethionine, a survey on localization techniques used up to now is given and their value and applications are discussed. Preoperative localization of parathyroid tissue should be limited to patients with previous unsuccessful surgery. In these cases we perform selective venous sampling following selective arteriography for demonstration of the venous drainage pattern and subsequent venous catheterization. Pneumomediastinography is recommended in suspected mediastinal parathyroid adenoma. Scanning with 75Se-selenomethionine is not in use because of its limited success.", "contents": "[Current status of preoperative localization in primary hyperparathyroidism (author's transl)]. Since Seldinger demonstrated in 1953 parathyroid adenomas by arteriography, numerous localizing procedures have been advocated. Based on our experience with selective venous sampling for measurement of parathyroid hormone by radioimmunoassay, selective arteriography, pneumomediastinography and scanning with 75Se-selenomethionine, a survey on localization techniques used up to now is given and their value and applications are discussed. Preoperative localization of parathyroid tissue should be limited to patients with previous unsuccessful surgery. In these cases we perform selective venous sampling following selective arteriography for demonstration of the venous drainage pattern and subsequent venous catheterization. Pneumomediastinography is recommended in suspected mediastinal parathyroid adenoma. Scanning with 75Se-selenomethionine is not in use because of its limited success."} {"id": "PMID:1273303", "title": "[Causes for vertebrobasilar artery insufficiency and reasons for misinterpretations in angiography (author's transl)].", "content": "Different morphological and functional causes of the vertebrobasilar artery insufficiency, which were found in the examination of 128 patients, were analyzed and compared with well known syndromes. Possible misinterpretation in evaluation of angiograms are emphasized.", "contents": "[Causes for vertebrobasilar artery insufficiency and reasons for misinterpretations in angiography (author's transl)]. Different morphological and functional causes of the vertebrobasilar artery insufficiency, which were found in the examination of 128 patients, were analyzed and compared with well known syndromes. Possible misinterpretation in evaluation of angiograms are emphasized."} {"id": "PMID:1273304", "title": "[Pheochromocytoma with scalloping of the ureter (author's transl)].", "content": "A case is described in which ureteral vascular impressions called \"notching\" or \"scalloping sign\" are caused by an ureteral artery supplying a pheochromocytoma. Vascular impressions on the ureter are recognized in different conditions. Most of them are due to collateral circulation following renal artery obstruction. The differential diagnosis is discussed.", "contents": "[Pheochromocytoma with scalloping of the ureter (author's transl)]. A case is described in which ureteral vascular impressions called \"notching\" or \"scalloping sign\" are caused by an ureteral artery supplying a pheochromocytoma. Vascular impressions on the ureter are recognized in different conditions. Most of them are due to collateral circulation following renal artery obstruction. The differential diagnosis is discussed."} {"id": "PMID:1273348", "title": "Statistical tables to detect significance between frequencies in two small samples, with particular reference to biological assays.", "content": "By simply referring to one of three tables, derived from Fisher's exact factorial method and obtained with the aid of a computer, it is possible to decide readily if differences observed between two small and equal or unequal size series are statistically significant at probability levels of 0.10, 0.05 and 0.01. The same can be very helpful for planning experiments. Examples are given in various fields of biology.", "contents": "Statistical tables to detect significance between frequencies in two small samples, with particular reference to biological assays. By simply referring to one of three tables, derived from Fisher's exact factorial method and obtained with the aid of a computer, it is possible to decide readily if differences observed between two small and equal or unequal size series are statistically significant at probability levels of 0.10, 0.05 and 0.01. The same can be very helpful for planning experiments. Examples are given in various fields of biology."} {"id": "PMID:1273349", "title": "[Effects of histones on phagocytosis and phagocytic metabolism].", "content": "Enhanced phagocytosis and no intracellular glycogen breakdown was found in guinea-pig peritoneal polymorphonuclear leukocytes (PMN) incubated together with heat-killed staphylococci (Twort) treated with a calf thymus histone fraction (P II), for 1 hr at 37 degrees C. Glcose consumption and lactate production of these PMN's were as high as in phagocytosis of the same germ untreated with P II, and their oxygen consumption was depressed significantly.", "contents": "[Effects of histones on phagocytosis and phagocytic metabolism]. Enhanced phagocytosis and no intracellular glycogen breakdown was found in guinea-pig peritoneal polymorphonuclear leukocytes (PMN) incubated together with heat-killed staphylococci (Twort) treated with a calf thymus histone fraction (P II), for 1 hr at 37 degrees C. Glcose consumption and lactate production of these PMN's were as high as in phagocytosis of the same germ untreated with P II, and their oxygen consumption was depressed significantly."} {"id": "PMID:1273350", "title": "[Influence of various enzyme inductors and combinations of inductors on DDT residue elimination in rats].", "content": "A study was under-taken to investigate the influence of pretreatments with various hepatic microsomal enzyme inducers on the elimination of DDT residues in rats previously contaminated with p,p' -DDT at 5 mg/kg/day, during 20 days. The following inducers were used : phenobarbital (50 a mg/kg/day, i.p.), 3,4-benzopyrene (20 mg/kg/day, s.c.) and norethandrolone (20 mg/kg/day, s.c.), all given during 14 consecutive days. Each inducer was administered singly or in combination with the other two according to a 2 X 2 X 2 factorial experiment. The animals were then sacrificed for the measurement of p,p' -DDT, p,p' -DDD and p,p' -DDE residues in the blood, brain, abdominal fat, liver and kidneys. The results show that phenobarbital lowers markedly the concentration of total residues in the fat tissue and brain and that norethandrolone brings about a reduction of the residues in the blood, brain and kidneys, but not in the fat tissue. On the opposite, 3,4-benzopyrene produces an increase of the residues in the brain, liver and kidneys. Phenobarbital thus appears to be more efficacious than the other two inducers in facilitating the elimination of DDT residues from the fat tissue. In addition, it appears that under the experimental conditions used during this investigation, the elimination of DDT residues is not further accelerated by combining the inducers one with each other.", "contents": "[Influence of various enzyme inductors and combinations of inductors on DDT residue elimination in rats]. A study was under-taken to investigate the influence of pretreatments with various hepatic microsomal enzyme inducers on the elimination of DDT residues in rats previously contaminated with p,p' -DDT at 5 mg/kg/day, during 20 days. The following inducers were used : phenobarbital (50 a mg/kg/day, i.p.), 3,4-benzopyrene (20 mg/kg/day, s.c.) and norethandrolone (20 mg/kg/day, s.c.), all given during 14 consecutive days. Each inducer was administered singly or in combination with the other two according to a 2 X 2 X 2 factorial experiment. The animals were then sacrificed for the measurement of p,p' -DDT, p,p' -DDD and p,p' -DDE residues in the blood, brain, abdominal fat, liver and kidneys. The results show that phenobarbital lowers markedly the concentration of total residues in the fat tissue and brain and that norethandrolone brings about a reduction of the residues in the blood, brain and kidneys, but not in the fat tissue. On the opposite, 3,4-benzopyrene produces an increase of the residues in the brain, liver and kidneys. Phenobarbital thus appears to be more efficacious than the other two inducers in facilitating the elimination of DDT residues from the fat tissue. In addition, it appears that under the experimental conditions used during this investigation, the elimination of DDT residues is not further accelerated by combining the inducers one with each other."} {"id": "PMID:1273351", "title": "A recording procedure for chronic microelectrodes in the paralyzed cat.", "content": "A method is described for repeated recording sessions of cortical thalamic units in the unanaesthetized but paralyzed animal. Because the recording chamber is miniaturized, it is well tolerated by the subject between sessions. The system also permits painless and stable immobilization of the head without the use of earbars, avoiding surgical preparation during the actual recording sessions and allowing long periods of recording. Between sessions the animals always display normal behavior.", "contents": "A recording procedure for chronic microelectrodes in the paralyzed cat. A method is described for repeated recording sessions of cortical thalamic units in the unanaesthetized but paralyzed animal. Because the recording chamber is miniaturized, it is well tolerated by the subject between sessions. The system also permits painless and stable immobilization of the head without the use of earbars, avoiding surgical preparation during the actual recording sessions and allowing long periods of recording. Between sessions the animals always display normal behavior."} {"id": "PMID:1273385", "title": "Role of peripheral and central chemosensitive afferents in the control of depth and frequency of breathing.", "content": "In anaesthetized cats the response to hypercapnia was studied during normoxia, hypoxia (increased peripheral chemosensitive afferents, IPA) and after carotid sinus denervation (decreased peripheral chemosensitive afferents, DPA) in terms of: (a) central output to the inspiratory muscles, (b) bulbopontine respiratory activity and (c) threshold-inhibition curve for termination of inspiration (Vr/Ti relationship). IPA increased, whereas DPA decreased the central output, as estimated from the rate of change of the subatmospheric pressure developed in the trachea during occlusion of the airways. IPA and DPA did not modify the bulbo-pontine rhythm, as estimated from the timing of occluded breaths (phasic vagal afferents nil), nor the Vt/Ti relationship, both of which have been shown to vary as a function of PACO2. It is concluded that peripheral chemosensitive afferents influence only the output of the respiratory centres, whereas central chemosensitive afferents influence also the bulbo-pontine respiratory rhythm and the threshold inhibition curve for termination of inspiration.", "contents": "Role of peripheral and central chemosensitive afferents in the control of depth and frequency of breathing. In anaesthetized cats the response to hypercapnia was studied during normoxia, hypoxia (increased peripheral chemosensitive afferents, IPA) and after carotid sinus denervation (decreased peripheral chemosensitive afferents, DPA) in terms of: (a) central output to the inspiratory muscles, (b) bulbopontine respiratory activity and (c) threshold-inhibition curve for termination of inspiration (Vr/Ti relationship). IPA increased, whereas DPA decreased the central output, as estimated from the rate of change of the subatmospheric pressure developed in the trachea during occlusion of the airways. IPA and DPA did not modify the bulbo-pontine rhythm, as estimated from the timing of occluded breaths (phasic vagal afferents nil), nor the Vt/Ti relationship, both of which have been shown to vary as a function of PACO2. It is concluded that peripheral chemosensitive afferents influence only the output of the respiratory centres, whereas central chemosensitive afferents influence also the bulbo-pontine respiratory rhythm and the threshold inhibition curve for termination of inspiration."} {"id": "PMID:1273386", "title": "Gas exchange in air sacs: contribution to respiratory gas exchange in ducks.", "content": "Air sac gas exchange was studied in ducks by measuring the rates of inert gas uptake and of O2 and CO2 equilibration in caudal thoracic air sac whose ventilation was prevented by surgival sealing of the ostia. The data were analyzed on a model incorporating three possible routes by which air sac gas could be exchanged with the surrounding tissue: (1) into the blood perfusing the air sac walls; (2) into the adjoining air sac via tissue membranes; (3) into the bronchial system of the lung via diffusion through lung tissue bordering upon the caudal thoracic air sac. Exchange rates of gases via the two latter paths were found to be small as compared with the first route. From application of model parameters to O2 and CO2 exchange in air sacs under physiological conditions the following conclusions were drawn: (1) the caudal thoracic air sac makes the major contribution to total gas exchange between air sacs and blood; (2) this exchange can account for less than 5% of total respiratory gas exchange; (3) the exchange is too small to account for the O2 and CO2 partial pressures in caudal thoracic air sacs of ducks. Other mechanisms like gas exchange in neopulmonic parabronchi, which conduct air to the caudal air sacs during inspiration or re-inspiration of dead space appear to play a more significant role in the deviation of O2 and CO2 partial pressures in the caudal air sacs from those in inspired air.", "contents": "Gas exchange in air sacs: contribution to respiratory gas exchange in ducks. Air sac gas exchange was studied in ducks by measuring the rates of inert gas uptake and of O2 and CO2 equilibration in caudal thoracic air sac whose ventilation was prevented by surgival sealing of the ostia. The data were analyzed on a model incorporating three possible routes by which air sac gas could be exchanged with the surrounding tissue: (1) into the blood perfusing the air sac walls; (2) into the adjoining air sac via tissue membranes; (3) into the bronchial system of the lung via diffusion through lung tissue bordering upon the caudal thoracic air sac. Exchange rates of gases via the two latter paths were found to be small as compared with the first route. From application of model parameters to O2 and CO2 exchange in air sacs under physiological conditions the following conclusions were drawn: (1) the caudal thoracic air sac makes the major contribution to total gas exchange between air sacs and blood; (2) this exchange can account for less than 5% of total respiratory gas exchange; (3) the exchange is too small to account for the O2 and CO2 partial pressures in caudal thoracic air sacs of ducks. Other mechanisms like gas exchange in neopulmonic parabronchi, which conduct air to the caudal air sacs during inspiration or re-inspiration of dead space appear to play a more significant role in the deviation of O2 and CO2 partial pressures in the caudal air sacs from those in inspired air."} {"id": "PMID:1273387", "title": "Mechanical activities of trachea as measured in vitro and in vivo.", "content": "The phenomenon of spontaneous contractions as measured in vivo and in vitro (isolated guinea pig trachea) is described. In vitro contractility is defined in terms of active tension (AT), the maximum rate of tension development (dT/dt) and time to peak tension (TTP). The length-tension relationship was established for spontaneous contractions of isolated guinea pig trachea. The effect of the temperature on spontaneous activities was also studied. An increase in temperature from 37.5 to 41.5C produced an increase in the maximum rate of tension development (dT/dt( and a decrease in the time to peak tension (TTP). A comparable decrease in temperature, from 37.5 to 33.5C produced slight but not statistically significa-nt increases in active tension, dT/dt and TTP. Frequency of the spontaneous contractions varied directly with changes in temperature. Employing a micro-strain-gauge transducer a rhytmic change of tracheal diameter has been observed in vivo in both guinea pigs and rabbits. Administration of atropine and isoproterenol in those experiments transiently abolished the appearance of these rhythmic changes of tracheal diameter.", "contents": "Mechanical activities of trachea as measured in vitro and in vivo. The phenomenon of spontaneous contractions as measured in vivo and in vitro (isolated guinea pig trachea) is described. In vitro contractility is defined in terms of active tension (AT), the maximum rate of tension development (dT/dt) and time to peak tension (TTP). The length-tension relationship was established for spontaneous contractions of isolated guinea pig trachea. The effect of the temperature on spontaneous activities was also studied. An increase in temperature from 37.5 to 41.5C produced an increase in the maximum rate of tension development (dT/dt( and a decrease in the time to peak tension (TTP). A comparable decrease in temperature, from 37.5 to 33.5C produced slight but not statistically significa-nt increases in active tension, dT/dt and TTP. Frequency of the spontaneous contractions varied directly with changes in temperature. Employing a micro-strain-gauge transducer a rhytmic change of tracheal diameter has been observed in vivo in both guinea pigs and rabbits. Administration of atropine and isoproterenol in those experiments transiently abolished the appearance of these rhythmic changes of tracheal diameter."} {"id": "PMID:1273388", "title": "The effect of emboli upon intrapulmonary receptors in the cat.", "content": "The effect of successive injections (on the activity from pulmonary stretch, irritant and type J receptors) of 0.1 g aliquots of either potato starch or plastic sheres was examined in artificially ventilated, anaesthetized, open chested cats. The discharge from nineteen pulmonary stretch receptors was altered after embolisation and mean maximum changes of 10% were observed in peak frequency and spike count per respiratory cycle. The activity from twelve of fourteen irritant receptors was changed after embolisation, mainly in the form of an increase of an existing, respiratory modulated discharge. O f ten type J receptors examined, six were stimulated after embolisation to produce an erratic pattern of discharge. The response of the three groups of receptors appeared to be independent of the size of the emboli. Histological examination showed scattered emboli in capillaries and columns in arterioles, according to particle size. It is likely that all three receptor types are involved in the reflex tachypnoea induced by pulmonary embolisation, since the changes in afferent vagal discharge occurred at or before the onset of the reflex respiratory events.", "contents": "The effect of emboli upon intrapulmonary receptors in the cat. The effect of successive injections (on the activity from pulmonary stretch, irritant and type J receptors) of 0.1 g aliquots of either potato starch or plastic sheres was examined in artificially ventilated, anaesthetized, open chested cats. The discharge from nineteen pulmonary stretch receptors was altered after embolisation and mean maximum changes of 10% were observed in peak frequency and spike count per respiratory cycle. The activity from twelve of fourteen irritant receptors was changed after embolisation, mainly in the form of an increase of an existing, respiratory modulated discharge. O f ten type J receptors examined, six were stimulated after embolisation to produce an erratic pattern of discharge. The response of the three groups of receptors appeared to be independent of the size of the emboli. Histological examination showed scattered emboli in capillaries and columns in arterioles, according to particle size. It is likely that all three receptor types are involved in the reflex tachypnoea induced by pulmonary embolisation, since the changes in afferent vagal discharge occurred at or before the onset of the reflex respiratory events."} {"id": "PMID:1273389", "title": "Increased elastic recoil as a determinant of pulmonary barotrauma in divers.", "content": "The elastic and conductive behaviour of the lungs were studied in sixteen divers during an interrupted deflation from total lung capacity (TLC.) The results in six divers, who had suffered pulmonary barotrauma (PBT) during shallow water diving, were compared with the findings in a control group of divers. Conductive behaviour and mean lung volumes were similar in the two groups. Compared with the control group, the PBT group had higher maximum transpulmonary pressures and a lower static pulmonary compliance, and deflated their lungs earlier. In relatively stiff lungs, an even distribution of elastance may increase susceptibility to barotrauma, because the more compliant zones are subjected to a greater strain. Pulmonary barotrauma appears to select from the total population of healthy divers those with lungs of decreased distensibility.", "contents": "Increased elastic recoil as a determinant of pulmonary barotrauma in divers. The elastic and conductive behaviour of the lungs were studied in sixteen divers during an interrupted deflation from total lung capacity (TLC.) The results in six divers, who had suffered pulmonary barotrauma (PBT) during shallow water diving, were compared with the findings in a control group of divers. Conductive behaviour and mean lung volumes were similar in the two groups. Compared with the control group, the PBT group had higher maximum transpulmonary pressures and a lower static pulmonary compliance, and deflated their lungs earlier. In relatively stiff lungs, an even distribution of elastance may increase susceptibility to barotrauma, because the more compliant zones are subjected to a greater strain. Pulmonary barotrauma appears to select from the total population of healthy divers those with lungs of decreased distensibility."} {"id": "PMID:1273390", "title": "Respiratory characteristics of blood from Basenji dogs with classical erythrocyte pyruvate kinase deficiency.", "content": "The oxygen affinities of blood from eight Basenji dogs homozygous for classical erythrocyte pyruvate kinase deficiency and four dogs heterozygous for the defect were compared with blood from 14 Labrador retrievers and two normal Basenji dogs. The homozygous dogs showed significant anemia compared to heterozygous and normal dogs (P is less than 0.01). The average blood P50 value (at 38C and plasma pH of 7.40) for both homozygous and heterozygous dogs was significantly higher (P is less than 0.01) than for normal dogs (33.6+/-0.4 and 31.8+/-0.7 vs 30.8+/-0.6 mm Hg). The concentrations of 2,3-DPG in the blood of both heterozygous and homozygous dogs were significantly higher than normal values. Four months after splenectomy P50 values declined to normal in four homozygous Basenji dogs without any change in the degree of anemia or blood 2,3-DPG concentrations. Iron kinetic studies showed a shorter plasma clearance time in a homozygous than in a normal dog with the heterozygote falling midway between. The red cell life span in the normal and heterozygous dogs was approximately 120 days. The 59Fe studies on the homozygous dog indicate markedly different survival characteristics which can be attributed to the existence of three populations of red cells differing in their life spans.", "contents": "Respiratory characteristics of blood from Basenji dogs with classical erythrocyte pyruvate kinase deficiency. The oxygen affinities of blood from eight Basenji dogs homozygous for classical erythrocyte pyruvate kinase deficiency and four dogs heterozygous for the defect were compared with blood from 14 Labrador retrievers and two normal Basenji dogs. The homozygous dogs showed significant anemia compared to heterozygous and normal dogs (P is less than 0.01). The average blood P50 value (at 38C and plasma pH of 7.40) for both homozygous and heterozygous dogs was significantly higher (P is less than 0.01) than for normal dogs (33.6+/-0.4 and 31.8+/-0.7 vs 30.8+/-0.6 mm Hg). The concentrations of 2,3-DPG in the blood of both heterozygous and homozygous dogs were significantly higher than normal values. Four months after splenectomy P50 values declined to normal in four homozygous Basenji dogs without any change in the degree of anemia or blood 2,3-DPG concentrations. Iron kinetic studies showed a shorter plasma clearance time in a homozygous than in a normal dog with the heterozygote falling midway between. The red cell life span in the normal and heterozygous dogs was approximately 120 days. The 59Fe studies on the homozygous dog indicate markedly different survival characteristics which can be attributed to the existence of three populations of red cells differing in their life spans."} {"id": "PMID:1273391", "title": "Convection, diffusion and cardiogenic mixing of inspired gas in the lung; an experimental approach.", "content": "In 8 open-chested dogs, we measured the FN2 within 26 airways, 2.5-8.6 mm in diameter, during constant flow inflations with 0.5 liter of O2. At low flows the FN2 did not fall to zero but reached a plateau, at a value that was inversely related to inspiratory flow. When inspiratory flow is constant, the measured FN2 represents one point on a stationary front separating inspired and alveolar gas. At all points on the front the convective and diffusive transport of N2 is equal and opposite in direction. We quantitated cardiogenic gas mixing by comparing in vivo and post mortem the flow which resulted in a given stable FN2 value within the same airway. In vivo, this flow and therefore the calculated effective diffusion coefficient (D') was more than 5 times greater than that post mortem. Our results confiem some of the predictions made from model analyses of gas transport in the lung. However, calculations based on molecular diffusion as the sole mixing mechanism necessarily overestimate diffusion times and the magnitude of stratification.", "contents": "Convection, diffusion and cardiogenic mixing of inspired gas in the lung; an experimental approach. In 8 open-chested dogs, we measured the FN2 within 26 airways, 2.5-8.6 mm in diameter, during constant flow inflations with 0.5 liter of O2. At low flows the FN2 did not fall to zero but reached a plateau, at a value that was inversely related to inspiratory flow. When inspiratory flow is constant, the measured FN2 represents one point on a stationary front separating inspired and alveolar gas. At all points on the front the convective and diffusive transport of N2 is equal and opposite in direction. We quantitated cardiogenic gas mixing by comparing in vivo and post mortem the flow which resulted in a given stable FN2 value within the same airway. In vivo, this flow and therefore the calculated effective diffusion coefficient (D') was more than 5 times greater than that post mortem. Our results confiem some of the predictions made from model analyses of gas transport in the lung. However, calculations based on molecular diffusion as the sole mixing mechanism necessarily overestimate diffusion times and the magnitude of stratification."} {"id": "PMID:1273392", "title": "Effects of local and systemic hypercapnia on the discharge of stretch receptors in the airways of the dog.", "content": "We have investigated the effects of local and systemic administration of 8% CO2 on the afferent discharge from slowly adapting stretch receptors located in a functionally isolated, in situ segment of trachea and extrapulmonary bronchi in dogs. Stretch receptors situated in the trachea were not affected by hypercapnia. Discharge from bronchial stretch receptors was diminished by local CO2 administration, especially at low airway transmural pressures. Systemic hypercapnia was generally ineffective. The results indicate that stretch receptors in extrapulmonary bronchi are more accessible to CO2 in the airway lumen than to perfusion with hypercapnic blood.", "contents": "Effects of local and systemic hypercapnia on the discharge of stretch receptors in the airways of the dog. We have investigated the effects of local and systemic administration of 8% CO2 on the afferent discharge from slowly adapting stretch receptors located in a functionally isolated, in situ segment of trachea and extrapulmonary bronchi in dogs. Stretch receptors situated in the trachea were not affected by hypercapnia. Discharge from bronchial stretch receptors was diminished by local CO2 administration, especially at low airway transmural pressures. Systemic hypercapnia was generally ineffective. The results indicate that stretch receptors in extrapulmonary bronchi are more accessible to CO2 in the airway lumen than to perfusion with hypercapnic blood."} {"id": "PMID:1273412", "title": "The enzymology of nasal secretion.", "content": "Normal human nasal fluid contains several enzymes of the intermediary metabolism as well as a specific protease inhibitor, which inhibits trypsinm chymotrypsin and leucocytic proteases. During the course of acute and chronic nasal and paransal sinus infections the inhibitor level varies. The inhibitor level is an indicator of poor healing. It is possible too, to differentiate viral rhinitis from bacterial or allergic or atrophic rhinitis by a signigicant increase of the activities of the enzymes GOT, LDH and CPK.", "contents": "The enzymology of nasal secretion. Normal human nasal fluid contains several enzymes of the intermediary metabolism as well as a specific protease inhibitor, which inhibits trypsinm chymotrypsin and leucocytic proteases. During the course of acute and chronic nasal and paransal sinus infections the inhibitor level varies. The inhibitor level is an indicator of poor healing. It is possible too, to differentiate viral rhinitis from bacterial or allergic or atrophic rhinitis by a signigicant increase of the activities of the enzymes GOT, LDH and CPK."} {"id": "PMID:1273413", "title": "Nasal cytology as a nasal test.", "content": "For years the presence of eosinophils has been considered a reliable diagnostic sign in the detection of nasal allergy, but little attention has been paid to the occurrence of other cellular elements. A complete study of hematogenic and epithelial cellular elements gives valuable information about the character of the rhinitis; i.e. is it caused by allergy or infection, or by both? The vitality of the mucosa, i.e. hyperfunction and atrophy, can also be assessed.", "contents": "Nasal cytology as a nasal test. For years the presence of eosinophils has been considered a reliable diagnostic sign in the detection of nasal allergy, but little attention has been paid to the occurrence of other cellular elements. A complete study of hematogenic and epithelial cellular elements gives valuable information about the character of the rhinitis; i.e. is it caused by allergy or infection, or by both? The vitality of the mucosa, i.e. hyperfunction and atrophy, can also be assessed."} {"id": "PMID:1273414", "title": "The diagnostic value of intranasal tests in allergic rhinopathy.", "content": "The method of the intranasal test, used by us, is described. It consists in a direct application of the allergen, which is presumed after a pilot-skin-test. The resulting reaction is documented by rhinomanometry. The special technical aspects of the test and the sources of error are emphasized.", "contents": "The diagnostic value of intranasal tests in allergic rhinopathy. The method of the intranasal test, used by us, is described. It consists in a direct application of the allergen, which is presumed after a pilot-skin-test. The resulting reaction is documented by rhinomanometry. The special technical aspects of the test and the sources of error are emphasized."} {"id": "PMID:1273417", "title": "Electromanometric function test of the nasofrontal duct.", "content": "An electromanometric methods for the quantitative measurement of the ventilation of the frontal sinus is described which also measures the resistance of the nasofrontal duct to an experimentally produced hydrodynamic current. The biophysical basis as well as typical results of the examination are demonstrated and the field of clinical application in the differential diagnosis of frontal sinus affections is outlined.", "contents": "Electromanometric function test of the nasofrontal duct. An electromanometric methods for the quantitative measurement of the ventilation of the frontal sinus is described which also measures the resistance of the nasofrontal duct to an experimentally produced hydrodynamic current. The biophysical basis as well as typical results of the examination are demonstrated and the field of clinical application in the differential diagnosis of frontal sinus affections is outlined."} {"id": "PMID:1273418", "title": "The present status of rhinomanometry.", "content": "Rhinomanometry is today a routine method that may be used in private specialist practice, if X-Y recording is used. The results become clinical statements only when directly compared with mirror findings, i.e. by functional analysis of structure or when physiological variance is taken into account by reagibility tests. In those cases this elegant technique becomes indeed indispensable.", "contents": "The present status of rhinomanometry. Rhinomanometry is today a routine method that may be used in private specialist practice, if X-Y recording is used. The results become clinical statements only when directly compared with mirror findings, i.e. by functional analysis of structure or when physiological variance is taken into account by reagibility tests. In those cases this elegant technique becomes indeed indispensable."} {"id": "PMID:1273474", "title": "[Chromatographic analysis of urinary amino acids in Paget's disease. I : Biochemical study. Isolation and amino acid composition of a urinary peptide specific to this bone disease].", "content": "The authors demonstrated in the urine of patients presenting Paget's bone disease a peptide rich in hydroxyproline. The level of this compound expressed as \"norleucine equivalent\" was determined by chromatographic analysis of the urinary amino acids. There was a very good correlation between the total hydroxyproline level and the quantity of this peptide in the urine. The authors isolated this peptide and determined that it contained 3 hydroxyprolines for every 2 glutamines. This peptide thus seems to indicate an anomaly in the chain of synthesis; a disorder of the collagen metabolism would produce in these patients large quantities of these molecules that are excreted via the kidney. At the present stage of the author's studies this urinary peptide appears to be \"specific\" to Pagets disease.", "contents": "[Chromatographic analysis of urinary amino acids in Paget's disease. I : Biochemical study. Isolation and amino acid composition of a urinary peptide specific to this bone disease]. The authors demonstrated in the urine of patients presenting Paget's bone disease a peptide rich in hydroxyproline. The level of this compound expressed as \"norleucine equivalent\" was determined by chromatographic analysis of the urinary amino acids. There was a very good correlation between the total hydroxyproline level and the quantity of this peptide in the urine. The authors isolated this peptide and determined that it contained 3 hydroxyprolines for every 2 glutamines. This peptide thus seems to indicate an anomaly in the chain of synthesis; a disorder of the collagen metabolism would produce in these patients large quantities of these molecules that are excreted via the kidney. At the present stage of the author's studies this urinary peptide appears to be \"specific\" to Pagets disease."} {"id": "PMID:1273475", "title": "[Chromatographic analysis of urinary amino acids in Paget's disease. II : clinical study].", "content": "The authors demonstrated in the urine of certain patients a peptide form of hydroxyproline and of glutamic acid. This peptide was found in patients with Paget's disease who presented clinical and laboratory signs of an evolutive episode and in other patients who presented restructuration of bone of a radiologicaly type. This peptide was one of the factors determining the increase in the total hydroxyprolinuria. The demonstration of the peptide provokes discussion as to its origin, and also of the possibility of using it as a biochemical parameter.", "contents": "[Chromatographic analysis of urinary amino acids in Paget's disease. II : clinical study]. The authors demonstrated in the urine of certain patients a peptide form of hydroxyproline and of glutamic acid. This peptide was found in patients with Paget's disease who presented clinical and laboratory signs of an evolutive episode and in other patients who presented restructuration of bone of a radiologicaly type. This peptide was one of the factors determining the increase in the total hydroxyprolinuria. The demonstration of the peptide provokes discussion as to its origin, and also of the possibility of using it as a biochemical parameter."} {"id": "PMID:1273476", "title": "[Periodic disease (familial paroxysmal polyseritis). 52 cases].", "content": "On the basis of well defined diagnostic criteria, the authors conclude that periodic disease affects males in particular. It commences before the age of 20 years in 80 percent of cases. In particular it occurs in Armenian and Shiite communities. Its evolution is normally benign ; amyloidosis is found in only 8 percent of cases. Joint manifestations are found in 48 percent of cases and may take on different aspects and occur in several different sites : myaglia or arthralgia, monoarthitis, oligoarthritis, polyarthritis, neck or sacroiliac pain. The authors have not noted prolonged peripheral joint episodes. No cases of amyloidosis were diagnosed before the appearance of the clinical signs of the disease. An autosomal, dominant heredity with incomplete penetration seems to be the most likely hypothesis.", "contents": "[Periodic disease (familial paroxysmal polyseritis). 52 cases]. On the basis of well defined diagnostic criteria, the authors conclude that periodic disease affects males in particular. It commences before the age of 20 years in 80 percent of cases. In particular it occurs in Armenian and Shiite communities. Its evolution is normally benign ; amyloidosis is found in only 8 percent of cases. Joint manifestations are found in 48 percent of cases and may take on different aspects and occur in several different sites : myaglia or arthralgia, monoarthitis, oligoarthritis, polyarthritis, neck or sacroiliac pain. The authors have not noted prolonged peripheral joint episodes. No cases of amyloidosis were diagnosed before the appearance of the clinical signs of the disease. An autosomal, dominant heredity with incomplete penetration seems to be the most likely hypothesis."} {"id": "PMID:1273477", "title": "[Xeroradiography : possibilities and value in osteo-articular pathology].", "content": "The authors report their first experiences with a new method of obtaining radiological information : radioxerography. Based on physical principles, replacing the older chemical basis, this new technique makes it possible to improve greatly, and with fewer exposures, the amount of information that can be obtained from radiological investigations. The advantages of the new method, based on the edge effect, the selectivity of the contours, and the spreading of the contrast, make possible much improved definition of both the bone structure and that of the neighbouring soft tissues. With reference to these first experiences, the authors summarize the possibilities and the preferred indications of the method, which although it remains a complementary and not a substitute method, appear very interesting and full of promise for the future.", "contents": "[Xeroradiography : possibilities and value in osteo-articular pathology]. The authors report their first experiences with a new method of obtaining radiological information : radioxerography. Based on physical principles, replacing the older chemical basis, this new technique makes it possible to improve greatly, and with fewer exposures, the amount of information that can be obtained from radiological investigations. The advantages of the new method, based on the edge effect, the selectivity of the contours, and the spreading of the contrast, make possible much improved definition of both the bone structure and that of the neighbouring soft tissues. With reference to these first experiences, the authors summarize the possibilities and the preferred indications of the method, which although it remains a complementary and not a substitute method, appear very interesting and full of promise for the future."} {"id": "PMID:1273478", "title": "[Dorsal tenosynovectomy of the wrist in rheumatoid arthritis. Results obtained in 30 cases].", "content": "With reference to a series of thirty synovectomies of the wrist in patients with rheumatoid arthritis, the authors report the results observed after an average interval of three years and six months. There was a remarkable reduction in pain in three-quarters of the cases. On the other hand, loss of mobility was noted in 15 patients. Resection of the cubital head was carried out in half of the cases. This was followed in two cases by internal translocation of the carpus, and in three cases by internal translocation combined with cubital inclination of the hand. The results of the tenddon repairs carried out in six patients have been completely satisfactory. A study of the present cases and of data from the literature confirms the local prophylactic value of tenosynovectomy which may also prevent tendon ruptures. The best result are seen in the less evolutive forms in which the risk of relapse is least, and in cases in which surgery is carried out on stable wrists with cartilage showing little alteration. In the presence of inferior radiocubital arthritis the resection must be systematic as it makes it possible to carry out a complete synovectomy of this joint. The authors compare the value of surgical synovectomy of the wrist with that of radioactive synoviorthesis.", "contents": "[Dorsal tenosynovectomy of the wrist in rheumatoid arthritis. Results obtained in 30 cases]. With reference to a series of thirty synovectomies of the wrist in patients with rheumatoid arthritis, the authors report the results observed after an average interval of three years and six months. There was a remarkable reduction in pain in three-quarters of the cases. On the other hand, loss of mobility was noted in 15 patients. Resection of the cubital head was carried out in half of the cases. This was followed in two cases by internal translocation of the carpus, and in three cases by internal translocation combined with cubital inclination of the hand. The results of the tenddon repairs carried out in six patients have been completely satisfactory. A study of the present cases and of data from the literature confirms the local prophylactic value of tenosynovectomy which may also prevent tendon ruptures. The best result are seen in the less evolutive forms in which the risk of relapse is least, and in cases in which surgery is carried out on stable wrists with cartilage showing little alteration. In the presence of inferior radiocubital arthritis the resection must be systematic as it makes it possible to carry out a complete synovectomy of this joint. The authors compare the value of surgical synovectomy of the wrist with that of radioactive synoviorthesis."} {"id": "PMID:1273483", "title": "[Antibody-dependent cytotoxicity of blood lymphocytes during rheumatoid polyarthritis].", "content": "Lymphocyte dependent-antibody cytotoxicity (LDAC) was studied in 29 patients with rheumatoid arthritis (RA) and 22 controls. A significant increase of cytotoxic index has been noted in RA patients (p less than 0.0001) whatever the ratio effector-target cells could be. There is a correlation between cytotoxic activity and so called \"rheumatoid rosettes\" (RR) level. This cytotoxic activity is linked to EA rosette forming cells without T cell markers or surface immunoglobulins, as shown by fractionation experiments. EA rosette forming cell depletion is followed by the disappearance of RR and a very important decrease of cytotoxic index. Cytotoxic activity is abolished after RR forming cell depletion while EA rosette level is nearly unmodified. RR forming cells belong to Fc receptor bearing lympho\u00efd population. They take place in EA rosette forming cell population. Increase of cytotoxicity in RA seems to be directly linked to these so called RR forming cells.", "contents": "[Antibody-dependent cytotoxicity of blood lymphocytes during rheumatoid polyarthritis]. Lymphocyte dependent-antibody cytotoxicity (LDAC) was studied in 29 patients with rheumatoid arthritis (RA) and 22 controls. A significant increase of cytotoxic index has been noted in RA patients (p less than 0.0001) whatever the ratio effector-target cells could be. There is a correlation between cytotoxic activity and so called \"rheumatoid rosettes\" (RR) level. This cytotoxic activity is linked to EA rosette forming cells without T cell markers or surface immunoglobulins, as shown by fractionation experiments. EA rosette forming cell depletion is followed by the disappearance of RR and a very important decrease of cytotoxic index. Cytotoxic activity is abolished after RR forming cell depletion while EA rosette level is nearly unmodified. RR forming cells belong to Fc receptor bearing lympho\u00efd population. They take place in EA rosette forming cell population. Increase of cytotoxicity in RA seems to be directly linked to these so called RR forming cells."} {"id": "PMID:1273484", "title": "[Use of Dodger filters in osteoarticular radiology].", "content": "Dodger filters represent considerable progress in the harmonization of the contrast in radiography by modulation of the incident Y-ray beam. The originality of these filters is related to three factors: the mobility of the filter elements, their shape, and in particular the presence of a specific optical system that makes it possible, by demonstrating the filter lines with a luminous ray, to predict and adapt the attenuation effects obtained. Osteo-articular radiology can now be viewed in a new light, as it is possible with Dodger filters to obtain on a single fim, valid images of the whole of the bony structure of a region as well as of the corresponding soft tissues.", "contents": "[Use of Dodger filters in osteoarticular radiology]. Dodger filters represent considerable progress in the harmonization of the contrast in radiography by modulation of the incident Y-ray beam. The originality of these filters is related to three factors: the mobility of the filter elements, their shape, and in particular the presence of a specific optical system that makes it possible, by demonstrating the filter lines with a luminous ray, to predict and adapt the attenuation effects obtained. Osteo-articular radiology can now be viewed in a new light, as it is possible with Dodger filters to obtain on a single fim, valid images of the whole of the bony structure of a region as well as of the corresponding soft tissues."} {"id": "PMID:1273485", "title": "[Radiologic study of the jaws in the course of myeloma. A propos of 111 cases].", "content": "The authors studied the radiological manifestations in bone in 111 patients suffering from multiple bone myeloma. The analysis deals mainly with the maxilla, and in particular with the lower maxilla which was the site of myelomatous lesions in 49 cases. The authors describe two different types of image observed and the radiological methods used, and they discuss the principal problems of diagnosis. They emphasize the diagnostic value of systematic study of this site, which may be solitary, without a concomitant lesion of the cranial dome in particular.", "contents": "[Radiologic study of the jaws in the course of myeloma. A propos of 111 cases]. The authors studied the radiological manifestations in bone in 111 patients suffering from multiple bone myeloma. The analysis deals mainly with the maxilla, and in particular with the lower maxilla which was the site of myelomatous lesions in 49 cases. The authors describe two different types of image observed and the radiological methods used, and they discuss the principal problems of diagnosis. They emphasize the diagnostic value of systematic study of this site, which may be solitary, without a concomitant lesion of the cranial dome in particular."} {"id": "PMID:1273490", "title": "Improved electrophoretic resolution of human serum alkaline phsophatase isoenzymes in agarose gel by Triton X-100.", "content": "Triton X-100 caused the liver isoenzymes of alkaline phosphatase in some serum samples to separate into two fractions on agarose gel electrophoresis. One of these fractions migrated at the rate of the original one, and one migrated more slowly. The latter fraction corresponded to a fast-moving component on electrophoresis in Cellogel and seems to be identical with a slowly moving isoenzyme in starch and polyacrylamide gel electrophoresis. The migration rates of the bone, placental, and intestinal isoenzymes were unaltered, but the fractions appeared sharper.", "contents": "Improved electrophoretic resolution of human serum alkaline phsophatase isoenzymes in agarose gel by Triton X-100. Triton X-100 caused the liver isoenzymes of alkaline phosphatase in some serum samples to separate into two fractions on agarose gel electrophoresis. One of these fractions migrated at the rate of the original one, and one migrated more slowly. The latter fraction corresponded to a fast-moving component on electrophoresis in Cellogel and seems to be identical with a slowly moving isoenzyme in starch and polyacrylamide gel electrophoresis. The migration rates of the bone, placental, and intestinal isoenzymes were unaltered, but the fractions appeared sharper."} {"id": "PMID:1273491", "title": "Endothelial and bile canalicular alkaline phosphatase in human liver and serum.", "content": "The alkaline phosphatase in homogenates of human liver was separated into two components by the addition of Triton X-100 to an agarose gel electrophoretic system. One of these components migrated at a rate identical to that of the original one and similar to alpha2-macroglobulin. The other component migrated more slowly, at a rate that resembled that of beta1-transferrin. Human serum samples regularly contained an identical fast-migrating fraction, whereas an identical slowly migrating fraction only appeared in serum obtained from patients with various diseases, especially from patients with malignant tumours, even though the liver did not contain tumour metastases. Slow isoenzyme was found in a few sera that had alkaline phosphatase activity within the normal range. Histochemical examinations of liver tissue from patients whose serum contained the slowly migrating isoenzyme showed a pronounced reaction of alkaline phosphatase in the bile canaliculi, and this isoenzyme seems to arise from the canaliculi. The fast-migrating isoenzyme might arise from the endothelial cells of the liver, to which the activity is usually confined in histochemical stainings.", "contents": "Endothelial and bile canalicular alkaline phosphatase in human liver and serum. The alkaline phosphatase in homogenates of human liver was separated into two components by the addition of Triton X-100 to an agarose gel electrophoretic system. One of these components migrated at a rate identical to that of the original one and similar to alpha2-macroglobulin. The other component migrated more slowly, at a rate that resembled that of beta1-transferrin. Human serum samples regularly contained an identical fast-migrating fraction, whereas an identical slowly migrating fraction only appeared in serum obtained from patients with various diseases, especially from patients with malignant tumours, even though the liver did not contain tumour metastases. Slow isoenzyme was found in a few sera that had alkaline phosphatase activity within the normal range. Histochemical examinations of liver tissue from patients whose serum contained the slowly migrating isoenzyme showed a pronounced reaction of alkaline phosphatase in the bile canaliculi, and this isoenzyme seems to arise from the canaliculi. The fast-migrating isoenzyme might arise from the endothelial cells of the liver, to which the activity is usually confined in histochemical stainings."} {"id": "PMID:1273492", "title": "The early serum insulin response to intravenous glucose in patients with decreased glucose tolerance and in subjects with a familial history of diabetes mellitus.", "content": "Intravenous glucose tolerance tests with estimations of K values and measurements of serum insulin concentrations at 0, 4, 6, and 8 min after the start of the glucose injection were performed in connection with a health examination survey of middle-aged men. The possible predictive value for later diabetes mellitus of early serum insulin response after intravenous glucose administration was evaluated by studying subjects with a familial history of diabetes mellitus and patients with different degrees of glucose intolerance. The following conclusions were drawn: The early appearance of glucose-stimulated serum insulin should be studied during the first 6 min after start of the glucose injection. The advantage of making calculations for early insulin secretion by including approximate considerations of the fractional removal rate of serum insulin is not apparent. Serum insulin values in patients with decreased glucose tolerance and subjects with a familial history of diabetes mellitus were best characterized by an insulin concentration index (glucose-stimulated early serum insulin concentration divided by basal serum insulin concentration). This index was significantly lower in these groups than in healthy controls.", "contents": "The early serum insulin response to intravenous glucose in patients with decreased glucose tolerance and in subjects with a familial history of diabetes mellitus. Intravenous glucose tolerance tests with estimations of K values and measurements of serum insulin concentrations at 0, 4, 6, and 8 min after the start of the glucose injection were performed in connection with a health examination survey of middle-aged men. The possible predictive value for later diabetes mellitus of early serum insulin response after intravenous glucose administration was evaluated by studying subjects with a familial history of diabetes mellitus and patients with different degrees of glucose intolerance. The following conclusions were drawn: The early appearance of glucose-stimulated serum insulin should be studied during the first 6 min after start of the glucose injection. The advantage of making calculations for early insulin secretion by including approximate considerations of the fractional removal rate of serum insulin is not apparent. Serum insulin values in patients with decreased glucose tolerance and subjects with a familial history of diabetes mellitus were best characterized by an insulin concentration index (glucose-stimulated early serum insulin concentration divided by basal serum insulin concentration). This index was significantly lower in these groups than in healthy controls."} {"id": "PMID:1273493", "title": "Further methodological studies on the intravenous fat tolerance with Intralipid emulsion.", "content": "Factors affecting the reproducibility of the intravenous fat tolerance test (IVFTT) with the Intralipid emulsion have been studied in man. Temperature variations of the emulsion at the time of injection did not affect the fractional removal rate k2. Plasma samples could be treated at room temperature without affecting the k2 value. Linear k2 slopes were obtained also in pronounced hypertriglyceridaemia, which suggests that the test can be applied in subjects with wide ranges of serum triglyceride (TG) concentrations. In subjects with a wide range of serum lipids but at steady state with regard to lipid metabolism, the IVFTT was found to be highly reproducible when repeated with intervals of up to 6 months. Furthermore, the turnover of serum TG, determined as the product of the fractional removal rate and the serum TG concentration, was constant. Most Intralipid batches gave identical k2 results. In some comparisons, batches were found which gave k2 curves significantly different from the standard batches. It is recommended that the IVFTT is carried out only with Intralipid emulsions that have been standardized in this respect.", "contents": "Further methodological studies on the intravenous fat tolerance with Intralipid emulsion. Factors affecting the reproducibility of the intravenous fat tolerance test (IVFTT) with the Intralipid emulsion have been studied in man. Temperature variations of the emulsion at the time of injection did not affect the fractional removal rate k2. Plasma samples could be treated at room temperature without affecting the k2 value. Linear k2 slopes were obtained also in pronounced hypertriglyceridaemia, which suggests that the test can be applied in subjects with wide ranges of serum triglyceride (TG) concentrations. In subjects with a wide range of serum lipids but at steady state with regard to lipid metabolism, the IVFTT was found to be highly reproducible when repeated with intervals of up to 6 months. Furthermore, the turnover of serum TG, determined as the product of the fractional removal rate and the serum TG concentration, was constant. Most Intralipid batches gave identical k2 results. In some comparisons, batches were found which gave k2 curves significantly different from the standard batches. It is recommended that the IVFTT is carried out only with Intralipid emulsions that have been standardized in this respect."} {"id": "PMID:1273494", "title": "The postanoxic regeneration of 5'-adenosine nucleotides in rabbit kidney tissue during in vitro perfusion.", "content": "The adenylate metabolism in rabbit kidney tissue was investigated, by isolated normothermic bloodless perfusion, during anoxic cell deterioration and postanoxic recovery in vitro. The amounts of hypoxanthine washed out during continuous anaerobic perfusion were shown to represent a definite loss of intracellular purine. No salvage of the endogenic liberated oxypurine was found to occur during postanoxic reoxygenation. The ability to restore the content of 5'-adenosine nucleotides failed after 60-120 min of anaerobic perfusion. Adenosine, adenine, inosine, hypoxanthine, and D-ribose added to the perfusate during reoxygenation were investigated with regard to their ability to stimulate postanoxic adenylate regeneration. Adenosine alone added in a concentration of more than 1 mmol/l showed a significant stimulation of the adenylate synthesis, with complete regeneration of the adenylate content after 180 min of preceding anoxia. In can be concluded that anoxia kidney deterioration is associated with a progressive loss of intracellular oxypurine, and a decreasing ability to regenerate adenylates after reoxygenation, which could be prevented by exogenic addition of adenosine. It appears reasonable to assume that the results obtained reflect the adenylate metabolism of a kidney graft during the postischaemic phase immediately after implantation.", "contents": "The postanoxic regeneration of 5'-adenosine nucleotides in rabbit kidney tissue during in vitro perfusion. The adenylate metabolism in rabbit kidney tissue was investigated, by isolated normothermic bloodless perfusion, during anoxic cell deterioration and postanoxic recovery in vitro. The amounts of hypoxanthine washed out during continuous anaerobic perfusion were shown to represent a definite loss of intracellular purine. No salvage of the endogenic liberated oxypurine was found to occur during postanoxic reoxygenation. The ability to restore the content of 5'-adenosine nucleotides failed after 60-120 min of anaerobic perfusion. Adenosine, adenine, inosine, hypoxanthine, and D-ribose added to the perfusate during reoxygenation were investigated with regard to their ability to stimulate postanoxic adenylate regeneration. Adenosine alone added in a concentration of more than 1 mmol/l showed a significant stimulation of the adenylate synthesis, with complete regeneration of the adenylate content after 180 min of preceding anoxia. In can be concluded that anoxia kidney deterioration is associated with a progressive loss of intracellular oxypurine, and a decreasing ability to regenerate adenylates after reoxygenation, which could be prevented by exogenic addition of adenosine. It appears reasonable to assume that the results obtained reflect the adenylate metabolism of a kidney graft during the postischaemic phase immediately after implantation."} {"id": "PMID:1273495", "title": "The influence of dye infusion rate and hepatic plasma flow on indocyanine green clearance.", "content": "The plasma clearance and extraction ratio of indocyanine green (ICG) were followed in cats anesthesized with chloralose. In one series of experiments the ICG infusion rate was raised stepwise and in another the hepatic plasma flow was changed by replacing part of the blood volume with erythrocytes, plasma, or dextran (Macrodex). For unknown reasons blood replacement with Macrodex increased the ICG elimination. Both plasma clearance and extraction ratio were independent of ICG infusion rate but dependent on hepatic plasma flow. In contrast, a clearance calculated from the dye elimination rate and the estimated average hepatic plasma concentration of ICG was independent of changes in hepatic plasma flow. In conclusion, plasma clearance and extraction ratio of indocyanine green are not ideal for estimation of liver function. However, when clearance is calculated from the average hepatic plasma concentration of the dye, it becomes independent of hepatic plasma flow and thus a more reliable index of liver function.", "contents": "The influence of dye infusion rate and hepatic plasma flow on indocyanine green clearance. The plasma clearance and extraction ratio of indocyanine green (ICG) were followed in cats anesthesized with chloralose. In one series of experiments the ICG infusion rate was raised stepwise and in another the hepatic plasma flow was changed by replacing part of the blood volume with erythrocytes, plasma, or dextran (Macrodex). For unknown reasons blood replacement with Macrodex increased the ICG elimination. Both plasma clearance and extraction ratio were independent of ICG infusion rate but dependent on hepatic plasma flow. In contrast, a clearance calculated from the dye elimination rate and the estimated average hepatic plasma concentration of ICG was independent of changes in hepatic plasma flow. In conclusion, plasma clearance and extraction ratio of indocyanine green are not ideal for estimation of liver function. However, when clearance is calculated from the average hepatic plasma concentration of the dye, it becomes independent of hepatic plasma flow and thus a more reliable index of liver function."} {"id": "PMID:1273496", "title": "Systematic difference of extrarenal background in left and right kidney regions at renography.", "content": "The problem of whether the extrarenal sodium [131I]iodohippurate background activity at renography is higher in the right kidney region than in the left was studied by analyzing data from 711 consecutive renographies. The 3 conical collimators had an aperture diameter of 78 mm, an internal diameter at crystal surface of 50 mm, and a skin-to-crystal surface distance of 115 mm, thus allowing the radioactivity of almost the entire kidney to be registered with equal efficiency.", "contents": "Systematic difference of extrarenal background in left and right kidney regions at renography. The problem of whether the extrarenal sodium [131I]iodohippurate background activity at renography is higher in the right kidney region than in the left was studied by analyzing data from 711 consecutive renographies. The 3 conical collimators had an aperture diameter of 78 mm, an internal diameter at crystal surface of 50 mm, and a skin-to-crystal surface distance of 115 mm, thus allowing the radioactivity of almost the entire kidney to be registered with equal efficiency."} {"id": "PMID:1273497", "title": "Influence of lactate infusion on glucose and FFA metabolism in man.", "content": "Sodium L(+)-lactate was infused at rates of 5 to 12 mmol/min intravenously for 30 min in health volunteers, and the exchange of lactate, glucose, and free fatty acids (FFA) was measured in the leg, the forearm muscle, and the splanchnic region. Arterial lactate levels were 3 to 5 mmol/l during the infusion. Leg blood flow increased about 2.5-fold and leg oxygen uptake rose by 35%. Blood flow, oxygen uptake, and glucose production in the splanchnic area remained unaltered. The fractional uptake of lactate by the leg, the splanchnic region, and the forearm decreased during the course of the infusion.", "contents": "Influence of lactate infusion on glucose and FFA metabolism in man. Sodium L(+)-lactate was infused at rates of 5 to 12 mmol/min intravenously for 30 min in health volunteers, and the exchange of lactate, glucose, and free fatty acids (FFA) was measured in the leg, the forearm muscle, and the splanchnic region. Arterial lactate levels were 3 to 5 mmol/l during the infusion. Leg blood flow increased about 2.5-fold and leg oxygen uptake rose by 35%. Blood flow, oxygen uptake, and glucose production in the splanchnic area remained unaltered. The fractional uptake of lactate by the leg, the splanchnic region, and the forearm decreased during the course of the infusion."} {"id": "PMID:1273499", "title": "A simple pressure calibrator.", "content": "A simple reliable, easy-to-use, and inexpensive device for obtaining any predetermined static gas pressure within +/- 35 cm H2O is described. It is suitalbe as a calibrator for pressure transducers as used in respiratory physiology. It is more convenient to use than an ordinary U-tube.", "contents": "A simple pressure calibrator. A simple reliable, easy-to-use, and inexpensive device for obtaining any predetermined static gas pressure within +/- 35 cm H2O is described. It is suitalbe as a calibrator for pressure transducers as used in respiratory physiology. It is more convenient to use than an ordinary U-tube."} {"id": "PMID:1273500", "title": "Serum bile acid concentration after a test meal.", "content": "Total serum bile acid concentrations were studied by an enzymatic-fluorimetric method employing a highly purified 3 alpha-hydroxysteroid dehydrogenase. In 28 control subjects mean total serum bile acid concentration was 2.5 mumoles/1 (S.D. 1.4). In 6 healthy subjects a significant postprandial increase in total serum bile acids occurred with maximal values at 90 and 120 minutes after ingestion of a liquid test meal. The maximal postprandial increase for each subject was 1.5 to 3 times the fasting value. In 7 patients with various hepatobiliary diseases the maximal postprandial elevation of serum bile acids was higher than in the normals, and the duration of serum bile acid elevation was significantly prolonged. In the patients with normal fasting concentration of bile acids the postprandial elevation was also significantly greater than in the controls. A 2-hour postprandial sample seems suitable for the study of the bile acid test meal response for clinical use.", "contents": "Serum bile acid concentration after a test meal. Total serum bile acid concentrations were studied by an enzymatic-fluorimetric method employing a highly purified 3 alpha-hydroxysteroid dehydrogenase. In 28 control subjects mean total serum bile acid concentration was 2.5 mumoles/1 (S.D. 1.4). In 6 healthy subjects a significant postprandial increase in total serum bile acids occurred with maximal values at 90 and 120 minutes after ingestion of a liquid test meal. The maximal postprandial increase for each subject was 1.5 to 3 times the fasting value. In 7 patients with various hepatobiliary diseases the maximal postprandial elevation of serum bile acids was higher than in the normals, and the duration of serum bile acid elevation was significantly prolonged. In the patients with normal fasting concentration of bile acids the postprandial elevation was also significantly greater than in the controls. A 2-hour postprandial sample seems suitable for the study of the bile acid test meal response for clinical use."} {"id": "PMID:1273501", "title": "Familial 'minor' adenomatous polyposis coli associated with gastric carcinoma - a hiterto undescribed phenotype of polyposis coli?", "content": "A clinical study of a family (Sch.) with a high incidence of death from gastric cancer in the second generation is presented. Endoscopic and/or surgical evaluation of the stomach, upper small intestine, and colon in 14 mainly asymptomatic members of the third and fourth generations revealed single or multiple (solitary) papillary adenomas in the colon or jejunum in 2 members each of the two generations. In addition, single or multiple hyperplastic polyps in the stomach or colon were found in 5 members, in 4 of them in association with papillary adenomas. The findings in family Sch. are consistent with 'minor' adenomatous polyposis coli associated with gastric carcinoma. Gastric carcinoma probably represents another phenotype among the vast variety of extra-colonic and extra-alimentary neoplastic changes known to occur in association with familial polyposis coli (FPC). The relationship of hyperplastic polyps to papillary adenoma in the colon and to gastric carcinoma respectively is discussed. Finally, evidence for a genetic relationship between family Sch. and a case with probable FPC is presented.", "contents": "Familial 'minor' adenomatous polyposis coli associated with gastric carcinoma - a hiterto undescribed phenotype of polyposis coli? A clinical study of a family (Sch.) with a high incidence of death from gastric cancer in the second generation is presented. Endoscopic and/or surgical evaluation of the stomach, upper small intestine, and colon in 14 mainly asymptomatic members of the third and fourth generations revealed single or multiple (solitary) papillary adenomas in the colon or jejunum in 2 members each of the two generations. In addition, single or multiple hyperplastic polyps in the stomach or colon were found in 5 members, in 4 of them in association with papillary adenomas. The findings in family Sch. are consistent with 'minor' adenomatous polyposis coli associated with gastric carcinoma. Gastric carcinoma probably represents another phenotype among the vast variety of extra-colonic and extra-alimentary neoplastic changes known to occur in association with familial polyposis coli (FPC). The relationship of hyperplastic polyps to papillary adenoma in the colon and to gastric carcinoma respectively is discussed. Finally, evidence for a genetic relationship between family Sch. and a case with probable FPC is presented."} {"id": "PMID:1273502", "title": "The diagnostic value of liver scanning. A retrospective study.", "content": "Among 650 consecutive radioisotope liver scans there were selected 180 representing all cases in which a pathoanatomical evaluation of the liver was available. The scanning data, the clinical information, and the pathoanatomical diagnosis were reviewed independently, and the results achieved in each group were classified as evidence of normal liver, focal hepatic disease, or diffuse hepatic disease. Using pathology for verification scanning had a sensitivity of 97% and a specificity of 90% regarding detection of unspecified liver disease, which was significantly better than clinical setting alone. In diffuse hepatic disease scanning had a sensitivity of 100% and a specificity of 81%, whereas in the focal hepatic disease the corresponding figures were 78 and 97%, respectively. Passive hepatic congestion was recognized as a diffuse hepatic disease by scanning, thus representing a source of error in screening for liver disease sensu stricto. It is concluded that scanning, apart from being a rapid and simple procedure without significant inconvenenience to the patient, is a very accurate diagnostic tool that deserves more recognition in clinical departments.", "contents": "The diagnostic value of liver scanning. A retrospective study. Among 650 consecutive radioisotope liver scans there were selected 180 representing all cases in which a pathoanatomical evaluation of the liver was available. The scanning data, the clinical information, and the pathoanatomical diagnosis were reviewed independently, and the results achieved in each group were classified as evidence of normal liver, focal hepatic disease, or diffuse hepatic disease. Using pathology for verification scanning had a sensitivity of 97% and a specificity of 90% regarding detection of unspecified liver disease, which was significantly better than clinical setting alone. In diffuse hepatic disease scanning had a sensitivity of 100% and a specificity of 81%, whereas in the focal hepatic disease the corresponding figures were 78 and 97%, respectively. Passive hepatic congestion was recognized as a diffuse hepatic disease by scanning, thus representing a source of error in screening for liver disease sensu stricto. It is concluded that scanning, apart from being a rapid and simple procedure without significant inconvenenience to the patient, is a very accurate diagnostic tool that deserves more recognition in clinical departments."} {"id": "PMID:1273503", "title": "Acid-base status in liver cirrhosis. Disturbances in stable, terminal and portal-caval shunted patients.", "content": "Acid-base status was determined in 86 patients with cirrhosis of the liver. Group I comprised 55 patients living more than 3 months after examination (stable). Another 18 stable patients with a surgical porta-caval shunt (p.c.a.) formed group II. Group III consisted of 12 terminal patients without p.c.a. examined within the last week of life. With respect to liver function group II was intermediate between I and III. The most common acid-base disturbance in group I was compensated respiratory alkalosis (20%) followed by compensated metabolic alkalosis (15%). 50% of group II presented compensated respiratory alkalosis. 85% of group III showed metabolic acidosis, which was compensated in only half of the patients. Respiratory alkalosis seemed more related to impairment of liver function than to portasystemic shunting. The genesis of the terminal metabolic acidosis was complex. Renal function was reduced in 92% of group III, and lactic acidosis was found in 36%. In this group hepatic function was most severely impaired, and 60% were hypotensive. These disturbances were not related to aetiology or treatment of the liver disease.", "contents": "Acid-base status in liver cirrhosis. Disturbances in stable, terminal and portal-caval shunted patients. Acid-base status was determined in 86 patients with cirrhosis of the liver. Group I comprised 55 patients living more than 3 months after examination (stable). Another 18 stable patients with a surgical porta-caval shunt (p.c.a.) formed group II. Group III consisted of 12 terminal patients without p.c.a. examined within the last week of life. With respect to liver function group II was intermediate between I and III. The most common acid-base disturbance in group I was compensated respiratory alkalosis (20%) followed by compensated metabolic alkalosis (15%). 50% of group II presented compensated respiratory alkalosis. 85% of group III showed metabolic acidosis, which was compensated in only half of the patients. Respiratory alkalosis seemed more related to impairment of liver function than to portasystemic shunting. The genesis of the terminal metabolic acidosis was complex. Renal function was reduced in 92% of group III, and lactic acidosis was found in 36%. In this group hepatic function was most severely impaired, and 60% were hypotensive. These disturbances were not related to aetiology or treatment of the liver disease."} {"id": "PMID:1273504", "title": "The demographic and social characteristics of patients with Crohn's disease in the Nottingham area.", "content": "All 260 patients diagnosed as having Crohn's disease between 1958 and 1973, in the Nottingham area, were sought and demographic and social characteristics obtained by personal interview. These were compared with the general population, using the 1971 census data. We found significantly high proportions of patients who were female; married; in the age groups 20-39 and 60-54; and in managerial or skilled manual occupations.", "contents": "The demographic and social characteristics of patients with Crohn's disease in the Nottingham area. All 260 patients diagnosed as having Crohn's disease between 1958 and 1973, in the Nottingham area, were sought and demographic and social characteristics obtained by personal interview. These were compared with the general population, using the 1971 census data. We found significantly high proportions of patients who were female; married; in the age groups 20-39 and 60-54; and in managerial or skilled manual occupations."} {"id": "PMID:1273505", "title": "The enteroglucagon response to intrajejunal infusion of glucose, triglycerides, and sodium chloride, and its relation to jejunal inhibition of gastric acid secretion in man.", "content": "In a previous communication we demonstrated that pentagastrin-induced gastric acid secretion is strongly and equally inhibited by intrajejunal infusions of hypertonic glucose, hypertonic sodium chloride, and triglycerides. Samples of peripheral venous blood obtained during these experiments were now analysed for insulin, glucose, pancreatic glucagon, and enteroglucagon. Pancreatic glucagon was stimulated weakly only by triglycerides. Enteroglucagon secretion was strongly stimulated by glucose, moderately by triglycerides, and unaltered after sodium chloride. Insulin secretion was stimulated only during the glucose infusion. We concluded that enteroglucagon is not responsible for the jejunal inhibition of gastric acid secretion in man by jejunal administration of hyperosmolal NaCl solution but may participate in the inhbition evoked by jejunal administration of glucose of triglycerides. Furthermore, it is unlikely that enteroglucagon is in itself insulinogenic in man.", "contents": "The enteroglucagon response to intrajejunal infusion of glucose, triglycerides, and sodium chloride, and its relation to jejunal inhibition of gastric acid secretion in man. In a previous communication we demonstrated that pentagastrin-induced gastric acid secretion is strongly and equally inhibited by intrajejunal infusions of hypertonic glucose, hypertonic sodium chloride, and triglycerides. Samples of peripheral venous blood obtained during these experiments were now analysed for insulin, glucose, pancreatic glucagon, and enteroglucagon. Pancreatic glucagon was stimulated weakly only by triglycerides. Enteroglucagon secretion was strongly stimulated by glucose, moderately by triglycerides, and unaltered after sodium chloride. Insulin secretion was stimulated only during the glucose infusion. We concluded that enteroglucagon is not responsible for the jejunal inhibition of gastric acid secretion in man by jejunal administration of hyperosmolal NaCl solution but may participate in the inhbition evoked by jejunal administration of glucose of triglycerides. Furthermore, it is unlikely that enteroglucagon is in itself insulinogenic in man."} {"id": "PMID:1273506", "title": "Immunological parameters, viral antibodies, and biochemical and histological findings in relatives of patients with chronic active hepatitis and primary biliary cirrhosis.", "content": "The familial occurrence of immunological, virological, biochemical and histopathological abnormalities has been studied in 39 first degree relatives of patients with primary biliary cirrhosis (PBC) and in 58 first degree relatives of patients with chronic active hepatitis (CAH). Tissue antibodies were more frequent in relatives than in age- and sex-matched controls. Abnormal immunoglobulin levels were demonstrated in about half of the relatives. Very high antibody titres to measles and rubella occurred only in the relatives of the patients with CAH. Moreover the raised titres tended to be clustered in a few families in which also the propositi had very high viral antibody titres. Liver biopsy was performed only on the relatives with biochemical abnormalities. Unspecific inflammatory changes were observed in 5 relatives of the patients with CAH and in 4 relatives of the patients with PBC. An active liver disease was detected in two relatives of the PBC-group and in one of the CAH-group. A marked accumulation of various immunological and histopathological abnormalities in four families was observed.", "contents": "Immunological parameters, viral antibodies, and biochemical and histological findings in relatives of patients with chronic active hepatitis and primary biliary cirrhosis. The familial occurrence of immunological, virological, biochemical and histopathological abnormalities has been studied in 39 first degree relatives of patients with primary biliary cirrhosis (PBC) and in 58 first degree relatives of patients with chronic active hepatitis (CAH). Tissue antibodies were more frequent in relatives than in age- and sex-matched controls. Abnormal immunoglobulin levels were demonstrated in about half of the relatives. Very high antibody titres to measles and rubella occurred only in the relatives of the patients with CAH. Moreover the raised titres tended to be clustered in a few families in which also the propositi had very high viral antibody titres. Liver biopsy was performed only on the relatives with biochemical abnormalities. Unspecific inflammatory changes were observed in 5 relatives of the patients with CAH and in 4 relatives of the patients with PBC. An active liver disease was detected in two relatives of the PBC-group and in one of the CAH-group. A marked accumulation of various immunological and histopathological abnormalities in four families was observed."} {"id": "PMID:1273507", "title": "On the mediation inflammatory reaction in the human gallbladder epithelium.", "content": "Human gallbladder epithelium was homogenized with a view to maintaining the integrity of subcellular components. In such homogenates, N-acetyl-beta-glucosaminidase, beta-glucuronidase, beta-galactosidase, beta-glucosidase, beta-fucosidase, beta-xylosidase, and acid phosphatase were demonstrated together with phospholipase activity. All the enzymes exhibited structure-linked latency. After discarding cellular debris from the homogenate, remaining subcellular organelles were analytically separated by density gradient centrifugation. After 100,000 g for 1 hour, particles containing acid glycosidases were recovered at a sucrose density of 1.18-1.19, whereas the mitochondrial marker enzyme succinate-reductase accumulated at a density of 1.16. The bulk of sedimentable phospholipase activity was recovered with particles sedimenting at 1.18-1.19. The results are interpreted as indicating that phosphalipase is present in lysosomes of the human gallbladder epithelium. Release of acid hydrolases, in lysosomes of the human gallbladder epithelium. Release of acid hydrolases, in lysosomes of the human gallbladder epithelium. Release of acid hydrolases, particularly phospholipase A, from the gallbladder epithelium is discussed as mediation of an inflammatory reaction in the gallbladder, i.e. cholecystitis.", "contents": "On the mediation inflammatory reaction in the human gallbladder epithelium. Human gallbladder epithelium was homogenized with a view to maintaining the integrity of subcellular components. In such homogenates, N-acetyl-beta-glucosaminidase, beta-glucuronidase, beta-galactosidase, beta-glucosidase, beta-fucosidase, beta-xylosidase, and acid phosphatase were demonstrated together with phospholipase activity. All the enzymes exhibited structure-linked latency. After discarding cellular debris from the homogenate, remaining subcellular organelles were analytically separated by density gradient centrifugation. After 100,000 g for 1 hour, particles containing acid glycosidases were recovered at a sucrose density of 1.18-1.19, whereas the mitochondrial marker enzyme succinate-reductase accumulated at a density of 1.16. The bulk of sedimentable phospholipase activity was recovered with particles sedimenting at 1.18-1.19. The results are interpreted as indicating that phosphalipase is present in lysosomes of the human gallbladder epithelium. Release of acid hydrolases, in lysosomes of the human gallbladder epithelium. Release of acid hydrolases, in lysosomes of the human gallbladder epithelium. Release of acid hydrolases, particularly phospholipase A, from the gallbladder epithelium is discussed as mediation of an inflammatory reaction in the gallbladder, i.e. cholecystitis."} {"id": "PMID:1273508", "title": "Effect of small bowel bypass on serum gastrin levels and gastric acid secretion in man.", "content": "In animals massive resection of the small intestine is followed by increased gastric acid secretion and an increase in serum gastrin levels. Whether hypersecretion occurs in man after intestinal resections or intestinal bypass is unclear, but an increase in fasting gastrin levels has been reported after intestinal resection. In this series a significant increase in basal gastric acid secretion and fasting serum gastrin levels has been demonstrated after intestinal bypass. However, none of the patients developed peptic ulcer or clinical symptoms of hypersecretion after the bypass operation. Whether the increase in basal secretion and the serum gastrin concentration are interrelated or of any clinical importance is uncertain.", "contents": "Effect of small bowel bypass on serum gastrin levels and gastric acid secretion in man. In animals massive resection of the small intestine is followed by increased gastric acid secretion and an increase in serum gastrin levels. Whether hypersecretion occurs in man after intestinal resections or intestinal bypass is unclear, but an increase in fasting gastrin levels has been reported after intestinal resection. In this series a significant increase in basal gastric acid secretion and fasting serum gastrin levels has been demonstrated after intestinal bypass. However, none of the patients developed peptic ulcer or clinical symptoms of hypersecretion after the bypass operation. Whether the increase in basal secretion and the serum gastrin concentration are interrelated or of any clinical importance is uncertain."} {"id": "PMID:1273509", "title": "Folic acid absorption in various gastrointestinal disorders.", "content": "In a consecutive study of 228 patients with folate deficiency originating from various gastrointestinal and haematological disorders, the clinical value of the folic acid absorption (TRIFA) test is assessed. It is concluded that the test is a simple, rapid, and reliable index for folic acid malabsorption of importance as well as a research tool as in daily practice.", "contents": "Folic acid absorption in various gastrointestinal disorders. In a consecutive study of 228 patients with folate deficiency originating from various gastrointestinal and haematological disorders, the clinical value of the folic acid absorption (TRIFA) test is assessed. It is concluded that the test is a simple, rapid, and reliable index for folic acid malabsorption of importance as well as a research tool as in daily practice."} {"id": "PMID:1273510", "title": "A controlled environmental culture system for the production of erythropoietin.", "content": "A controlled environmental culture system in which consistent growth of fetal liver cells typical of the tissue of origin and capable of producing erythropoietin in culture is described. This system attempts to duplicate the major components of the natural habitat of the mammalian cell allowing for meaningful studies to be conducted on the regulation and control of erythropoietin biosynthesis. The direct effects of changes in pO2, pCO2, pH and various cell nutrients on cells producing erythropoietin is now possible.", "contents": "A controlled environmental culture system for the production of erythropoietin. A controlled environmental culture system in which consistent growth of fetal liver cells typical of the tissue of origin and capable of producing erythropoietin in culture is described. This system attempts to duplicate the major components of the natural habitat of the mammalian cell allowing for meaningful studies to be conducted on the regulation and control of erythropoietin biosynthesis. The direct effects of changes in pO2, pCO2, pH and various cell nutrients on cells producing erythropoietin is now possible."} {"id": "PMID:1273511", "title": "Rarity of anaemia of pregnancy in Ethiopia.", "content": "Hb and PCV values were studied in three groups of Addis Ababa women during their last month of pregnancy and compared with those in a control group of non-pregnant Addis Ababa women. Irrespective of socio-economic group and parity, the Hb and PCV values were almost identical in all four groups. In one of the three test groups, a group of 'non-privileged' multiparae, S-iron, S-transferrin (TIBC), S-folate and S-vitamin B12 were also examined and showed normal values. These findings indicate a rarity not only of true anaemia but also of 'physiological anaemia of pregnancy'. This latter may not, therefore, be an adaptive phenomenon of regular occurrence as has usually been assumed hitherto. The explanation for the aberrant haematological behavior in pregnant women living in highland Ethiopia is probably the lifelong exposure to a very high iron intake combined with hypoxia due to the high altitude.", "contents": "Rarity of anaemia of pregnancy in Ethiopia. Hb and PCV values were studied in three groups of Addis Ababa women during their last month of pregnancy and compared with those in a control group of non-pregnant Addis Ababa women. Irrespective of socio-economic group and parity, the Hb and PCV values were almost identical in all four groups. In one of the three test groups, a group of 'non-privileged' multiparae, S-iron, S-transferrin (TIBC), S-folate and S-vitamin B12 were also examined and showed normal values. These findings indicate a rarity not only of true anaemia but also of 'physiological anaemia of pregnancy'. This latter may not, therefore, be an adaptive phenomenon of regular occurrence as has usually been assumed hitherto. The explanation for the aberrant haematological behavior in pregnant women living in highland Ethiopia is probably the lifelong exposure to a very high iron intake combined with hypoxia due to the high altitude."} {"id": "PMID:1273512", "title": "Studies on lymphocytes XIII. Nuclear volume measurement as a rapid approach to estimate proliferative fraction.", "content": "A rapid method for measuring volume distributions of human, calf and goat lymphocytes and their nuclei is described along with the type of quantitation these measurements can provide by computer analysis. The size distribution studies indicate the presence of two populations of lymphocytes and their nuclei irrespective of the cell source. It is suggested that proliferative fractions of various cell populations may be estimated by determining the nuclear volume distribution.", "contents": "Studies on lymphocytes XIII. Nuclear volume measurement as a rapid approach to estimate proliferative fraction. A rapid method for measuring volume distributions of human, calf and goat lymphocytes and their nuclei is described along with the type of quantitation these measurements can provide by computer analysis. The size distribution studies indicate the presence of two populations of lymphocytes and their nuclei irrespective of the cell source. It is suggested that proliferative fractions of various cell populations may be estimated by determining the nuclear volume distribution."} {"id": "PMID:1273513", "title": "Acquired thrombophilia: a hitherto unrecognized procoagulant-antithrombin imbalance.", "content": "Inherited, acquired and iatrogenic 'diseases of low antithrombin activity' share a common denominator: each is associated with an increased tendency toward, or incidence of, thrombosis. This suggested the possibility that these diseases constituted a distinct pathogenetic entity. Molecular models and clinical studies suggested 3 interrelated phenomena: increased serum procoagulants; decreased antithrombin; a tendency to thrombosis. The term 'Acquired Thrombophilia' is proposed to designate pre-thrombotic and thrombotic individuals presenting this non-inherited combination of laboratory and clinical findings. The antithrombin clotting time is shown to be inversely related to the level of circulating serine procoagulants, directly related to the level of antithrombin, and results from a procoagulant-antithrombin inter-molecular reaction. Patients with Acquired Thrombophilia have 'turned-on' or excessive procoagulants resulting in 'turned-off' or tightly bound antithrombin molecules.", "contents": "Acquired thrombophilia: a hitherto unrecognized procoagulant-antithrombin imbalance. Inherited, acquired and iatrogenic 'diseases of low antithrombin activity' share a common denominator: each is associated with an increased tendency toward, or incidence of, thrombosis. This suggested the possibility that these diseases constituted a distinct pathogenetic entity. Molecular models and clinical studies suggested 3 interrelated phenomena: increased serum procoagulants; decreased antithrombin; a tendency to thrombosis. The term 'Acquired Thrombophilia' is proposed to designate pre-thrombotic and thrombotic individuals presenting this non-inherited combination of laboratory and clinical findings. The antithrombin clotting time is shown to be inversely related to the level of circulating serine procoagulants, directly related to the level of antithrombin, and results from a procoagulant-antithrombin inter-molecular reaction. Patients with Acquired Thrombophilia have 'turned-on' or excessive procoagulants resulting in 'turned-off' or tightly bound antithrombin molecules."} {"id": "PMID:1273514", "title": "Thrombocytopenia in childhood: an evaluation of 433 patients.", "content": "An evaluation of 433 children with thrombocytopenia is presented. The material comprises all cases diagnosed in Denmark during the period 1959-1969. The incidence was found to be 31.9 cases per 1,000,000 inhabitants less than or equal to 15 years of age per annum with a peak at the age of 3 to 4 years; the majority of the cases was diagnosed in the spring. Preceding infection, usually associated with fever and localized in the upper respiratory tract, was the most common cause. The majority of the congenital cases was hereditary and associated with other malformations involving in particular the immune system. In about half of the cases the course was spontaneous and no treatment was necessary; the remaining patients were treated with glucocorticoids, including 46 patients, who had undergone splenectomy. 22 patients died, including 16 cases due to serious underlying disorders; in 6 cases the cause of death was haemorrhage (mortality rat=1.4%). At the follow up the platelet count was below 50 mia/1 in 14 patients (4%). No difference was found concerning the platelet count at the follow up between the patients with spontaneous recovery, the patients treated with glucocorticoids and the patients, in whom splenectomy had been performed. During the course the disease autoimmune haemolytic anaemia occurred in 2 patients, whereas no patient developed systemic lupus erythematosus.", "contents": "Thrombocytopenia in childhood: an evaluation of 433 patients. An evaluation of 433 children with thrombocytopenia is presented. The material comprises all cases diagnosed in Denmark during the period 1959-1969. The incidence was found to be 31.9 cases per 1,000,000 inhabitants less than or equal to 15 years of age per annum with a peak at the age of 3 to 4 years; the majority of the cases was diagnosed in the spring. Preceding infection, usually associated with fever and localized in the upper respiratory tract, was the most common cause. The majority of the congenital cases was hereditary and associated with other malformations involving in particular the immune system. In about half of the cases the course was spontaneous and no treatment was necessary; the remaining patients were treated with glucocorticoids, including 46 patients, who had undergone splenectomy. 22 patients died, including 16 cases due to serious underlying disorders; in 6 cases the cause of death was haemorrhage (mortality rat=1.4%). At the follow up the platelet count was below 50 mia/1 in 14 patients (4%). No difference was found concerning the platelet count at the follow up between the patients with spontaneous recovery, the patients treated with glucocorticoids and the patients, in whom splenectomy had been performed. During the course the disease autoimmune haemolytic anaemia occurred in 2 patients, whereas no patient developed systemic lupus erythematosus."} {"id": "PMID:1273515", "title": "Immunoelectrophoretic 'tailing' of albumin line due to albumin-IgG antibody complexes: a side effect of nitrofurantoin treatment?", "content": "The immunochemical analysis of sera of 10 patients in which immunoelectrophoresis showed a cathodic, elongated, 'tailing' albumin (TA) line is described. Eight of the 10 patients had been treated with nitrofurantoin, and withdrawal of the drug was followed by disappearance of the phenomenon in 5 cases. Most of the patients had polyclonally elevated IgG and IgA levels and a decreased albumin level; IgM; C3, C4, and C1-INH were normal. Antinuclear activity of IgG type was demonstrated in the sera of 9 patients. The TA phenomenon was due to noncovalently bound complexes between IgG and albumin. The combining sites of the IgG molecules were in the Fab fragment. The antibody-like activity of the IgG was directed towards autologous albumin. The anti-albumin activity remained unchanged after absorption of the antinuclear activity. The nitrofurantoin-induced albumin-anti-albumin system may prove useful as a human model of autoimmune response of known aetiology.", "contents": "Immunoelectrophoretic 'tailing' of albumin line due to albumin-IgG antibody complexes: a side effect of nitrofurantoin treatment? The immunochemical analysis of sera of 10 patients in which immunoelectrophoresis showed a cathodic, elongated, 'tailing' albumin (TA) line is described. Eight of the 10 patients had been treated with nitrofurantoin, and withdrawal of the drug was followed by disappearance of the phenomenon in 5 cases. Most of the patients had polyclonally elevated IgG and IgA levels and a decreased albumin level; IgM; C3, C4, and C1-INH were normal. Antinuclear activity of IgG type was demonstrated in the sera of 9 patients. The TA phenomenon was due to noncovalently bound complexes between IgG and albumin. The combining sites of the IgG molecules were in the Fab fragment. The antibody-like activity of the IgG was directed towards autologous albumin. The anti-albumin activity remained unchanged after absorption of the antinuclear activity. The nitrofurantoin-induced albumin-anti-albumin system may prove useful as a human model of autoimmune response of known aetiology."} {"id": "PMID:1273516", "title": "Synthesis of secretory component by human colon cancer cells.", "content": "Colon carcinoma, established in long-term tissue culture, has been shown to synthesize secretory component (SC). These molecules can be demonstrated both on the cell surface and in the cytoplasm by immunofluorescence. Regeneration of SC was demonstrable after trypsinization of the cells. In culture, two lines of carcinoma epithelium were shown to incorporate (14C) leucine into newly synthesized SC. These cell lines should provide useful preparations for studying the details of immunoglobulin-SC interactions.", "contents": "Synthesis of secretory component by human colon cancer cells. Colon carcinoma, established in long-term tissue culture, has been shown to synthesize secretory component (SC). These molecules can be demonstrated both on the cell surface and in the cytoplasm by immunofluorescence. Regeneration of SC was demonstrable after trypsinization of the cells. In culture, two lines of carcinoma epithelium were shown to incorporate (14C) leucine into newly synthesized SC. These cell lines should provide useful preparations for studying the details of immunoglobulin-SC interactions."} {"id": "PMID:1273517", "title": "The role of adherent cells in the immune response. Fibroblasts and products released by fibroblasts and peritoneal cells can substitute for adherent cells.", "content": "The primary immune response to sheep erythrocytes in adherent cell-depleted cultures was restored by adding a critical number of peritoneal cells. Complete substitution was achieved also with supernatants from allogeneic and syngeneic peritoneal cells. Both living fibroblasts and supernatants from fibroblast cultures were found to be highly efficient substitutes for adherent cells in both syngeneic and allogeneic systems. Supernatants from non-antigen-reated peritoneal cells and fibroblasts caused increased DNA synthesis and induction of polyclonal antibody synthesis in normal spleen cells. Thus, adherent cells need not function in the immune response by presenting antigen to the B cells via 'IgT' or by releasing signal-2 activity, which acts on lymphocytes that have already received signal 1.", "contents": "The role of adherent cells in the immune response. Fibroblasts and products released by fibroblasts and peritoneal cells can substitute for adherent cells. The primary immune response to sheep erythrocytes in adherent cell-depleted cultures was restored by adding a critical number of peritoneal cells. Complete substitution was achieved also with supernatants from allogeneic and syngeneic peritoneal cells. Both living fibroblasts and supernatants from fibroblast cultures were found to be highly efficient substitutes for adherent cells in both syngeneic and allogeneic systems. Supernatants from non-antigen-reated peritoneal cells and fibroblasts caused increased DNA synthesis and induction of polyclonal antibody synthesis in normal spleen cells. Thus, adherent cells need not function in the immune response by presenting antigen to the B cells via 'IgT' or by releasing signal-2 activity, which acts on lymphocytes that have already received signal 1."} {"id": "PMID:1273518", "title": "A Clq immunosorbent assay compared with thin-layer gel filtration for measuring IgG aggregates.", "content": "A new sensitive technique measures C1q-binding of human IgG aggregates. The method is based on the principle of the enzyme-linked immunosorbent assay with C1q-coated tubes. The IgG aggregates attaching to this C1q are shown by enzyme-linked anti-human IgG. Less than 0.01 mug of aggregates per milliliter of sample can be detected. The results with this new method showed significant correlation (P less than 0.01; Spearman rank correlation test) with the estimates of IgG aggregates of 13S or more and 10S in size obtained by thin-layer gel filtration. Both of these methods showed significant correlation with the classic hemolysis inhibition method for measuring complement fixation.", "contents": "A Clq immunosorbent assay compared with thin-layer gel filtration for measuring IgG aggregates. A new sensitive technique measures C1q-binding of human IgG aggregates. The method is based on the principle of the enzyme-linked immunosorbent assay with C1q-coated tubes. The IgG aggregates attaching to this C1q are shown by enzyme-linked anti-human IgG. Less than 0.01 mug of aggregates per milliliter of sample can be detected. The results with this new method showed significant correlation (P less than 0.01; Spearman rank correlation test) with the estimates of IgG aggregates of 13S or more and 10S in size obtained by thin-layer gel filtration. Both of these methods showed significant correlation with the classic hemolysis inhibition method for measuring complement fixation."} {"id": "PMID:1273519", "title": "A comparison of four methods for measuring cutaneous delayed- type hypersensitivity reactions to protein antigens in the mouse.", "content": "Delayed-type hypersensitivity was induced in mice by injecting keyhole limpet haemocyanin or human serum albumin in Freund's complete adjuvant. Four techniques for assessing specific skin reactions in these immunized animals were compared: increase in thickness of the footpad; increase in thickness of the ear; arrival of 51Cr-labelled syngeneic lymph node cells at the challenge site in the ear; and accumulation of (125I)IUdR at the challenge site in the ear. The most sensitive and reliable test for detecting strong and weak reactions proved to be measurement of antigen-induced thickening in the ear.", "contents": "A comparison of four methods for measuring cutaneous delayed- type hypersensitivity reactions to protein antigens in the mouse. Delayed-type hypersensitivity was induced in mice by injecting keyhole limpet haemocyanin or human serum albumin in Freund's complete adjuvant. Four techniques for assessing specific skin reactions in these immunized animals were compared: increase in thickness of the footpad; increase in thickness of the ear; arrival of 51Cr-labelled syngeneic lymph node cells at the challenge site in the ear; and accumulation of (125I)IUdR at the challenge site in the ear. The most sensitive and reliable test for detecting strong and weak reactions proved to be measurement of antigen-induced thickening in the ear."} {"id": "PMID:1273520", "title": "Bacteroides bacteraemia. A clinical and bacteriological analysis of 51 patients.", "content": "During a 7-year period Bacteroides bacteraemia was found in 51 patients, corresponding to 1.9% of all patients with positive blood cultures. Many patients had serious underlying diseases, most frequently in the gastrointestinal tract, and 80% were subjected to surgery. Frequent clinical findings were shock (27%), phlebitis (24%) and jaundice (22%). The overall mortality was 55%. Increased mortality was associated with shock, advanced age and phlebitis. Bacteroides fragilis, showing a very homogeneous biochemical pattern, was the species most frequently isolated. The strains were sensitive to chloramphenicol and tetracycline, and as a rule also to erythromycin. It was confirmed that Bacteroides isolated from the blood usually indicates true bacteraemia.", "contents": "Bacteroides bacteraemia. A clinical and bacteriological analysis of 51 patients. During a 7-year period Bacteroides bacteraemia was found in 51 patients, corresponding to 1.9% of all patients with positive blood cultures. Many patients had serious underlying diseases, most frequently in the gastrointestinal tract, and 80% were subjected to surgery. Frequent clinical findings were shock (27%), phlebitis (24%) and jaundice (22%). The overall mortality was 55%. Increased mortality was associated with shock, advanced age and phlebitis. Bacteroides fragilis, showing a very homogeneous biochemical pattern, was the species most frequently isolated. The strains were sensitive to chloramphenicol and tetracycline, and as a rule also to erythromycin. It was confirmed that Bacteroides isolated from the blood usually indicates true bacteraemia."} {"id": "PMID:1273521", "title": "Treatment of oral candidiasis in debilitated patients with miconazole--a new potent antifungal drug.", "content": "In 24 patients with advanced malignant diseases, mainly leukaemias and lymphomas, 35 episodes of oral candidiasis were treated with topical application of miconazole. Clinical cures were obtained in 100% of the episodes and mycological cures in 91% of the episodes after a mean treatment time of only 4.9 days, although most of the patients were severely granulocytopenic and were undergoing simultaneous treatment with cytostatics, prednisolone and antibiotics. Miconazole appears to be a remarkably fast-acting, reliable and non-toxic drug in the treatment of oral candidiasis.", "contents": "Treatment of oral candidiasis in debilitated patients with miconazole--a new potent antifungal drug. In 24 patients with advanced malignant diseases, mainly leukaemias and lymphomas, 35 episodes of oral candidiasis were treated with topical application of miconazole. Clinical cures were obtained in 100% of the episodes and mycological cures in 91% of the episodes after a mean treatment time of only 4.9 days, although most of the patients were severely granulocytopenic and were undergoing simultaneous treatment with cytostatics, prednisolone and antibiotics. Miconazole appears to be a remarkably fast-acting, reliable and non-toxic drug in the treatment of oral candidiasis."} {"id": "PMID:1273524", "title": "Tuberculin anergy in patients with Mycoplasma pneumoniae infection.", "content": "Skin testing for delayed hypersensitivity to tuberculin was performed in 36 patients with pneumonia associated with Mycoplasma pneumoniae infection. 22 of these patients had a negative tuberculin reaction when first tested. The tuberculin reaction was negative in 13 out of 16 cases tested during the first 2 weeks after onset of illness, in 6 out of 11 cases tested 15-28 days after onset of illness and in 3 out of 9 cases tested 29-45 days after clinical onset. In 19 patients with a negative tuberculin test in the early phase after onset of illness the test was repeated several weeks or months later. 16 of these cases had a positive tuberculin reaction at the later time period. Two of these cases showed prolonged tuberculin anergy for more than 5 months.", "contents": "Tuberculin anergy in patients with Mycoplasma pneumoniae infection. Skin testing for delayed hypersensitivity to tuberculin was performed in 36 patients with pneumonia associated with Mycoplasma pneumoniae infection. 22 of these patients had a negative tuberculin reaction when first tested. The tuberculin reaction was negative in 13 out of 16 cases tested during the first 2 weeks after onset of illness, in 6 out of 11 cases tested 15-28 days after onset of illness and in 3 out of 9 cases tested 29-45 days after clinical onset. In 19 patients with a negative tuberculin test in the early phase after onset of illness the test was repeated several weeks or months later. 16 of these cases had a positive tuberculin reaction at the later time period. Two of these cases showed prolonged tuberculin anergy for more than 5 months."} {"id": "PMID:1273526", "title": "Bacterial endocarditis at Blegdamshospitalet in Copenhagen 1944-1973.", "content": "The clinical pattern of 34 cases ob subacute bacterial endocarditis (SBE) and 46 cases of acute bacterial endocarditis (ABE) is outlined. In the SBE group the mortality was 9% and the incidence of major complications during the treatment period was 15% for cerebrovascular accidents, 9% for other systemic or pulmonary emboli and 9% for congestive heart failure indicating valvular damage. In 31 bacteriologically proven cases growth was obtained in 68% of all blood cultures, and in 94% of the cases at least one positive culture was among the first 5 ones drawn. In the ABE group the overall mortality was 72% and mortality for cases occurring after 1960 was 58%. Major factors contributing to death were valvular incompetence, uncontrolled infection and embolisation. In order to reduce major complications and resulting disability in SBE it is suggested that treatment be started on clinical suspicion as soon as 5 blood cultures have been drawn over a period of 48 hours. Attempts to reduce mortality in ABE may include cardiac surgery in the acute phase.", "contents": "Bacterial endocarditis at Blegdamshospitalet in Copenhagen 1944-1973. The clinical pattern of 34 cases ob subacute bacterial endocarditis (SBE) and 46 cases of acute bacterial endocarditis (ABE) is outlined. In the SBE group the mortality was 9% and the incidence of major complications during the treatment period was 15% for cerebrovascular accidents, 9% for other systemic or pulmonary emboli and 9% for congestive heart failure indicating valvular damage. In 31 bacteriologically proven cases growth was obtained in 68% of all blood cultures, and in 94% of the cases at least one positive culture was among the first 5 ones drawn. In the ABE group the overall mortality was 72% and mortality for cases occurring after 1960 was 58%. Major factors contributing to death were valvular incompetence, uncontrolled infection and embolisation. In order to reduce major complications and resulting disability in SBE it is suggested that treatment be started on clinical suspicion as soon as 5 blood cultures have been drawn over a period of 48 hours. Attempts to reduce mortality in ABE may include cardiac surgery in the acute phase."} {"id": "PMID:1273527", "title": "Induratio penis plastica Peyronie's disease. Clinical features and etiology.", "content": "The clinical and laboratory findings in 106 patients with Peyronie's disease as well as histopathological examinations of biopsies from the plaques were studied. The clinical symptoms and signs were in general similar to those found in previous studies, but bone marrow smears showed an increased number of plasma cells and lymphocytes in 18 of 24 examined. Biopsy of the plaque in cases of long-term symptomatology disclosed a fibrosis poor in cellular components. In patients with a short history of the disease and a tender induration, an inflammatory component of the specimens with perivascular accumulation of lymphocytes and balooning of endothelial cells in the small vessels was seen. Characteristic cells with \"cross-banded\" nuclei, described earlier only in Dupuytren's contracture and experimental fibrosis, was observed for the first time in Peyronie's disease. Based on these findings a combined traumatic-immunological etiology is suggested.", "contents": "Induratio penis plastica Peyronie's disease. Clinical features and etiology. The clinical and laboratory findings in 106 patients with Peyronie's disease as well as histopathological examinations of biopsies from the plaques were studied. The clinical symptoms and signs were in general similar to those found in previous studies, but bone marrow smears showed an increased number of plasma cells and lymphocytes in 18 of 24 examined. Biopsy of the plaque in cases of long-term symptomatology disclosed a fibrosis poor in cellular components. In patients with a short history of the disease and a tender induration, an inflammatory component of the specimens with perivascular accumulation of lymphocytes and balooning of endothelial cells in the small vessels was seen. Characteristic cells with \"cross-banded\" nuclei, described earlier only in Dupuytren's contracture and experimental fibrosis, was observed for the first time in Peyronie's disease. Based on these findings a combined traumatic-immunological etiology is suggested."} {"id": "PMID:1273528", "title": "Induration penis plastica. Experience of treatment with procarbazine Natulan.", "content": "Eighteen patients with plastic induration of the penis were treated with procarbazine, a cytotoxic agent. Ten patients experienced a good to excellent result; 7 patients no improvement and in one patient treatment had to be prematurely withdrawn because of gastro-intestinal side-effects. No other serious side-effects occurred in the present investigation. Patients with impaired erection, previous gastric surgery and alcoholics are deemed less suitable for this form of therapy. It can be recommended to other patients in otherwise good condition and is especially suitable when diffuse fibrosis is present or when cavernosography indicates deep infiltration of the disease into the intercavernous septum. Selection can be made from those patients who show no tendency to spontaneous remission or those unsuitable for or unresponsive to other therapeutic measures.", "contents": "Induration penis plastica. Experience of treatment with procarbazine Natulan. Eighteen patients with plastic induration of the penis were treated with procarbazine, a cytotoxic agent. Ten patients experienced a good to excellent result; 7 patients no improvement and in one patient treatment had to be prematurely withdrawn because of gastro-intestinal side-effects. No other serious side-effects occurred in the present investigation. Patients with impaired erection, previous gastric surgery and alcoholics are deemed less suitable for this form of therapy. It can be recommended to other patients in otherwise good condition and is especially suitable when diffuse fibrosis is present or when cavernosography indicates deep infiltration of the disease into the intercavernous septum. Selection can be made from those patients who show no tendency to spontaneous remission or those unsuitable for or unresponsive to other therapeutic measures."} {"id": "PMID:1273529", "title": "A controlled investigation of the value of anticoagulant therapy in cases of prostatectomy.", "content": "Prior to prostatectomy, 182 patients were classified into two groups of 90 and 92 patients. The classification was performed so as to make the groups mutually comparable with respect to factors considered significant in connection with the risk of thrombo-embolism. The group with 90 patients was anticoagulated with marcoumar. The other group served as a control. There was no significant difference in mortality or thrombosis incidence between the two groups. There was a significantly larger loss of blood in the anticoagulated group. Five of the patients in the anticoagulated group died, while in the control group, 3 patients died. Epsilon-aminocaproic acid was not used on a routine basis.", "contents": "A controlled investigation of the value of anticoagulant therapy in cases of prostatectomy. Prior to prostatectomy, 182 patients were classified into two groups of 90 and 92 patients. The classification was performed so as to make the groups mutually comparable with respect to factors considered significant in connection with the risk of thrombo-embolism. The group with 90 patients was anticoagulated with marcoumar. The other group served as a control. There was no significant difference in mortality or thrombosis incidence between the two groups. There was a significantly larger loss of blood in the anticoagulated group. Five of the patients in the anticoagulated group died, while in the control group, 3 patients died. Epsilon-aminocaproic acid was not used on a routine basis."} {"id": "PMID:1273530", "title": "Vascular resistance in hypothermically perfused kidneys damaged by warm ischemia.", "content": "Vascular resistance was determined during hypothermic perfusion of rabbit kidneys after various periods of warm ischemia. Ischemia was induced by clamping of the renal artery, or of the renal artery and vein, in situ. Studies were made after periods of clamping ranging from 0 to 180 min. The perfusing fluid was 5% Dextran of low molecular weight in balanced saline solution (Tis-U-Sol), with addition of 5 mg % Papaverin. When the renal artery was clamped for more than 15 min, vascular resistance increased. Maximal resistance was reached after 60 min of clamping, and was 3 times as high as that value in the control group of kidneys which were not clamped. The vascular resistance attained after 60 min of clamping did not further increase when clamping was maintained for 180 min. When both the renal artery and the renal vein were clamped vascular resistance first increased after 30 min. Maximal resistance was reached after 60 min of clamping, but was only 1/2 of that level seen when the renal artery alone was clamped.", "contents": "Vascular resistance in hypothermically perfused kidneys damaged by warm ischemia. Vascular resistance was determined during hypothermic perfusion of rabbit kidneys after various periods of warm ischemia. Ischemia was induced by clamping of the renal artery, or of the renal artery and vein, in situ. Studies were made after periods of clamping ranging from 0 to 180 min. The perfusing fluid was 5% Dextran of low molecular weight in balanced saline solution (Tis-U-Sol), with addition of 5 mg % Papaverin. When the renal artery was clamped for more than 15 min, vascular resistance increased. Maximal resistance was reached after 60 min of clamping, and was 3 times as high as that value in the control group of kidneys which were not clamped. The vascular resistance attained after 60 min of clamping did not further increase when clamping was maintained for 180 min. When both the renal artery and the renal vein were clamped vascular resistance first increased after 30 min. Maximal resistance was reached after 60 min of clamping, but was only 1/2 of that level seen when the renal artery alone was clamped."} {"id": "PMID:1273531", "title": "The influence of an agonal phase on the vascular resistance of the kidney measured during hypothermic perfusion studies.", "content": "The influence of the agonal phase on the rabbit renal vascular resistance during warm ischemia was studied in 24 hypothermic perfusion experiments. The agonal phase was induced by tracheal clamping in anesthetized animals. The interval from strangulation to cardiac arrest was, on average, 8.1 min. Kidneys were removed between 0 and 60 min after cardiac arrest. Comparison with an earlier study where warm ischemia was induced by clamping of the renal artery shows that the agonal phase is not a significant factor in that renal vascular resistance is not increased.", "contents": "The influence of an agonal phase on the vascular resistance of the kidney measured during hypothermic perfusion studies. The influence of the agonal phase on the rabbit renal vascular resistance during warm ischemia was studied in 24 hypothermic perfusion experiments. The agonal phase was induced by tracheal clamping in anesthetized animals. The interval from strangulation to cardiac arrest was, on average, 8.1 min. Kidneys were removed between 0 and 60 min after cardiac arrest. Comparison with an earlier study where warm ischemia was induced by clamping of the renal artery shows that the agonal phase is not a significant factor in that renal vascular resistance is not increased."} {"id": "PMID:1273532", "title": "The effect of temporary clamping of the renal vessels on the vascular resistance in rabbit kidneys.", "content": "In studies of 45 rabbits, either the renal artery (35 animals), or the renal artery and vein (10 animals) were clamped in situ. The effect of the clamping--of the warm ischemia--on the vascular resistance of the kidney after reestablishment of the circulation was examined in perfusion studies made after removal of the kidneys from groups of 5 animals between 1 and 5 days after revascularization. Resistance patterns were measured during hypothermic perfusion. The results confirm earlier findings that vascular resistance increases in proportion to the duration of warm ischemia up to 60 min, but not thereafter. The renal vascular resistance falls over the days following revascularization, more slowly after longer periods of ischemia. Thus after 60 min of warm ischemia the vascular resistance became normal within 24 hours, but after 180 min of warm ischemia, the normal resistance range was not reached until 96 hours after reestablishment of the circulation. When both the renal artery and the renal vein were clamped, the pattern was the same but much less emphatic. The vascular resistance never attained such high values as seen after clamping of the renal artery alone, and became normal after 24 hours of revascularization, even when the period of warm ischemia was as long as 180 min.", "contents": "The effect of temporary clamping of the renal vessels on the vascular resistance in rabbit kidneys. In studies of 45 rabbits, either the renal artery (35 animals), or the renal artery and vein (10 animals) were clamped in situ. The effect of the clamping--of the warm ischemia--on the vascular resistance of the kidney after reestablishment of the circulation was examined in perfusion studies made after removal of the kidneys from groups of 5 animals between 1 and 5 days after revascularization. Resistance patterns were measured during hypothermic perfusion. The results confirm earlier findings that vascular resistance increases in proportion to the duration of warm ischemia up to 60 min, but not thereafter. The renal vascular resistance falls over the days following revascularization, more slowly after longer periods of ischemia. Thus after 60 min of warm ischemia the vascular resistance became normal within 24 hours, but after 180 min of warm ischemia, the normal resistance range was not reached until 96 hours after reestablishment of the circulation. When both the renal artery and the renal vein were clamped, the pattern was the same but much less emphatic. The vascular resistance never attained such high values as seen after clamping of the renal artery alone, and became normal after 24 hours of revascularization, even when the period of warm ischemia was as long as 180 min."} {"id": "PMID:1273533", "title": "Effect of splenectomy on anemia in patients on regular dialysis treatment.", "content": "Splenectomy was performed in 7 patients on regular hemodialysis treatment who had disabling anemia. All patients had a short 51Cr red cell survival time and an increased splenic uptake of red cells verified by external counting and computer-aided scintigraphy. The need for blood-transfusions was eliminated in all except one. In all patients the hemoglobin concentration rose after splenectomy. This was probably an effect of a reduced plasma volume and the removal of a large pool of non-circulating red cells. No consistent changes in the red blood cell survival time or the red cell volume were observed. The white cell and the platelet counts in the blood rose to twice the preoperative value. No adverse effect of the splenectomy was observed.", "contents": "Effect of splenectomy on anemia in patients on regular dialysis treatment. Splenectomy was performed in 7 patients on regular hemodialysis treatment who had disabling anemia. All patients had a short 51Cr red cell survival time and an increased splenic uptake of red cells verified by external counting and computer-aided scintigraphy. The need for blood-transfusions was eliminated in all except one. In all patients the hemoglobin concentration rose after splenectomy. This was probably an effect of a reduced plasma volume and the removal of a large pool of non-circulating red cells. No consistent changes in the red blood cell survival time or the red cell volume were observed. The white cell and the platelet counts in the blood rose to twice the preoperative value. No adverse effect of the splenectomy was observed."} {"id": "PMID:1273534", "title": "Skeletal status in patients with chronic renal disease.", "content": "The bone mineral content (BMC) was measured in 17 patients with chronic renal failure. The patients as a group had a mean BMC of 89% compared with 127 normal subjects. The investigation failed to disclose any significant correlation between BMC and the stage of renal diseases.", "contents": "Skeletal status in patients with chronic renal disease. The bone mineral content (BMC) was measured in 17 patients with chronic renal failure. The patients as a group had a mean BMC of 89% compared with 127 normal subjects. The investigation failed to disclose any significant correlation between BMC and the stage of renal diseases."} {"id": "PMID:1273535", "title": "Subcutaneous arteriovenous fistulas for dialysis with special emphasis on vascular insufficiency.", "content": "Ninety-four subcutaneous arterio-venous fistulas were created for haemodialysis in 83 patients. Seventy-one patients eventually received well-functioning fistulas. The most common complication was thrombosis at the suture line. Thus, 8 primary fistulas clotted within 24 hours of surgery and 5 clotted later. Eleven patients were reoperated with a successful result in six. One patient developed arterial insufficiency in the hand with finger ulcerations, probably due to a radial steal syndrome. Four patients got extremely swollen hands and threatening gangraena because of thrombosis of the vein proximally to the anastomosis. Vital capillary microscopy in the patients with vascular insufficiency demonstrated profound changes of the nutritional capillaries which were not seen in control patients with well-functioning fistulas. After closure of the fistulas the edema disappeared and the ulcerations healed rapidly.", "contents": "Subcutaneous arteriovenous fistulas for dialysis with special emphasis on vascular insufficiency. Ninety-four subcutaneous arterio-venous fistulas were created for haemodialysis in 83 patients. Seventy-one patients eventually received well-functioning fistulas. The most common complication was thrombosis at the suture line. Thus, 8 primary fistulas clotted within 24 hours of surgery and 5 clotted later. Eleven patients were reoperated with a successful result in six. One patient developed arterial insufficiency in the hand with finger ulcerations, probably due to a radial steal syndrome. Four patients got extremely swollen hands and threatening gangraena because of thrombosis of the vein proximally to the anastomosis. Vital capillary microscopy in the patients with vascular insufficiency demonstrated profound changes of the nutritional capillaries which were not seen in control patients with well-functioning fistulas. After closure of the fistulas the edema disappeared and the ulcerations healed rapidly."} {"id": "PMID:1273536", "title": "Experience with arteriovenous fistulas CIMINO in chronic hemodialysis. A report on forty-five patients.", "content": "Experiences with 45 uremic patients with arteriovenous fistulas for dialysis are described. The operation is easy and successful if the vessels of the patient are intact. Varicose syndromes of the hand may occur but can be managed. Complications from cannulations, such as large hematomas, are rare but may obstruct otherwise good fistulas. The fistula should be constructed in good time before a definite need for dialysis arises.", "contents": "Experience with arteriovenous fistulas CIMINO in chronic hemodialysis. A report on forty-five patients. Experiences with 45 uremic patients with arteriovenous fistulas for dialysis are described. The operation is easy and successful if the vessels of the patient are intact. Varicose syndromes of the hand may occur but can be managed. Complications from cannulations, such as large hematomas, are rare but may obstruct otherwise good fistulas. The fistula should be constructed in good time before a definite need for dialysis arises."} {"id": "PMID:1273537", "title": "Duplication of the male urethra treated by septotomy. A case report.", "content": "In a case of incomplete duplication of the male urethra the interurethral septum was divided by scissors. After this simple operative procedure, the patient was relieved of his obstructive symptoms. Postoperative urethrography revealed considerable improvement of the calibre of the urethral lumen, and uroflowmetry showed almost normalized flow values. This technique is recommended as treatment in similar cases.", "contents": "Duplication of the male urethra treated by septotomy. A case report. In a case of incomplete duplication of the male urethra the interurethral septum was divided by scissors. After this simple operative procedure, the patient was relieved of his obstructive symptoms. Postoperative urethrography revealed considerable improvement of the calibre of the urethral lumen, and uroflowmetry showed almost normalized flow values. This technique is recommended as treatment in similar cases."} {"id": "PMID:1273538", "title": "Giant vesical calculas and anuria.", "content": "A 50-year-old fisherman developed uremia and anuria, due to a giant vesical calculus. He was treated with suprapubic lithotomy, and a calculus weighing 1 640 g was removed. This may be the largest calculus ever removed with recovery of the patient. No other reports of giant stones leading to anuria has been found in the available literature. More than 4 years later an inoperable carcinoma of the bladder was discovered. The long delay in diagnosis of the giant stone, as later of the carcinoma, was due to the patient's lack of confidence in doctors and hospitals.", "contents": "Giant vesical calculas and anuria. A 50-year-old fisherman developed uremia and anuria, due to a giant vesical calculus. He was treated with suprapubic lithotomy, and a calculus weighing 1 640 g was removed. This may be the largest calculus ever removed with recovery of the patient. No other reports of giant stones leading to anuria has been found in the available literature. More than 4 years later an inoperable carcinoma of the bladder was discovered. The long delay in diagnosis of the giant stone, as later of the carcinoma, was due to the patient's lack of confidence in doctors and hospitals."} {"id": "PMID:1273539", "title": "Partial hydronephrosis in a patient with horseshoe kidney and bilateral duplication of the pelvis and ureter.", "content": "A case of the rare combination of horseshoe kidney, bilateral duplication of the pelvis and ureter, with stricture of one uretero-pelvic junction causing symptomatic hydronephrosis is reported. The patient was treated with resection as modum Anderson-Hynes. The embryology, symptomatology and treatment of such anomalies is discussed.", "contents": "Partial hydronephrosis in a patient with horseshoe kidney and bilateral duplication of the pelvis and ureter. A case of the rare combination of horseshoe kidney, bilateral duplication of the pelvis and ureter, with stricture of one uretero-pelvic junction causing symptomatic hydronephrosis is reported. The patient was treated with resection as modum Anderson-Hynes. The embryology, symptomatology and treatment of such anomalies is discussed."} {"id": "PMID:1273540", "title": "Influence of posture on pulmonary gas exchange and heart rate in chronic obstructive lung disease.", "content": "Sixteen subjects with chronic obstructive lung disease were studied in supine and sitting position. VT, VE, VD and VD/VT were definitely higher in the sitting position (p less than 0.001). PaCO2 was slightly lower in the sitting position, whereas Pa\u00bfO2 was the same in both positions. P(A-a)O2 was essentially the same in both positions, but the estimated QS/QT was definitely lower in the sitting position. In patients with low FEV1.0 the heart rate showed a tendency towards higher values in the sitting position.", "contents": "Influence of posture on pulmonary gas exchange and heart rate in chronic obstructive lung disease. Sixteen subjects with chronic obstructive lung disease were studied in supine and sitting position. VT, VE, VD and VD/VT were definitely higher in the sitting position (p less than 0.001). PaCO2 was slightly lower in the sitting position, whereas Pa\u00bfO2 was the same in both positions. P(A-a)O2 was essentially the same in both positions, but the estimated QS/QT was definitely lower in the sitting position. In patients with low FEV1.0 the heart rate showed a tendency towards higher values in the sitting position."} {"id": "PMID:1273541", "title": "Comparison of infused and inhaled terbutaline in patients with asthma.", "content": "Skeletal muscle tremor is the most common side effect when giving the relatively selective beta2-adrenergic-stimulators. Tachycardia is a side effect which limits dosage in a few patients only. Dose-reponse relation was tested on ventilatory capacity, heart rate, blood pressure and skeletal muscle tremor after terbutaline was given intravenously and as an aerosol. Terbutaline infusions in doses exceeding the recommended therapeutic level did not produce maximal relaxation of the bronchial muscle in patients with endogenous asthma, but increased the heart rate by 25 beats per minute and more than doubled the tremor. The tachycardia is mainly due to peripheral vasodilation and reflexogenic heart stimulation. Terbutaline given by inhalation produced the same bronchial relaxation without any effect on heart rate, blood pressure of tremor, indicating a local effect. The acute margin of safety was notable; the increase of pulse after 63 inhalations of this long-acting substance being only 16 beats per minutes.", "contents": "Comparison of infused and inhaled terbutaline in patients with asthma. Skeletal muscle tremor is the most common side effect when giving the relatively selective beta2-adrenergic-stimulators. Tachycardia is a side effect which limits dosage in a few patients only. Dose-reponse relation was tested on ventilatory capacity, heart rate, blood pressure and skeletal muscle tremor after terbutaline was given intravenously and as an aerosol. Terbutaline infusions in doses exceeding the recommended therapeutic level did not produce maximal relaxation of the bronchial muscle in patients with endogenous asthma, but increased the heart rate by 25 beats per minute and more than doubled the tremor. The tachycardia is mainly due to peripheral vasodilation and reflexogenic heart stimulation. Terbutaline given by inhalation produced the same bronchial relaxation without any effect on heart rate, blood pressure of tremor, indicating a local effect. The acute margin of safety was notable; the increase of pulse after 63 inhalations of this long-acting substance being only 16 beats per minutes."} {"id": "PMID:1273542", "title": "Scanning of viscosity in sputum.", "content": "A viscometer for measurement of sputum viscosity is described. The apparatus makes possible continuous measurement of sputum samples from 5 to 50 ml in volume. It has been calibrated against capillary and rotation viscometers with excellent correlation. The recordings obtained from sputum impressively display the heterogeneity of this material. They render the possibility of calculating a mean viscosity and of plotting the viscometer are given and the relationship between this instrument and other types of viscometers is discussed.", "contents": "Scanning of viscosity in sputum. A viscometer for measurement of sputum viscosity is described. The apparatus makes possible continuous measurement of sputum samples from 5 to 50 ml in volume. It has been calibrated against capillary and rotation viscometers with excellent correlation. The recordings obtained from sputum impressively display the heterogeneity of this material. They render the possibility of calculating a mean viscosity and of plotting the viscometer are given and the relationship between this instrument and other types of viscometers is discussed."} {"id": "PMID:1273543", "title": "Exercise-related changes in plasma levels of 15-keto-13,14-dihydro-prostaglandin F2alpha and noradrenaline in asthmatic and normal subjects.", "content": "In an attempt to elucidate the roles of prostaglandin F2alpha and noradrenaline in exercise-induced asthma, plasma levels of these substances were measured at rest, during and after exercise in normal and asthmatic subjects. Changes in airways resistance were assessed by measuring the peak expiratory flow rate. Plasma levels of 15-keto-13,14-dihydro-prostaglandin F2alpha (a relatively stable metabolite of prostaglandin F2alpha) and noradrenaline, at rest, and the changes that occurred during and after exercise, were similar in both the normal and asthmatic subjects. Exercise-induced broncho-constriction occurred in all asthmatic subjects following exercise while no significant change occurred in the peak expiratory flow rates of the normal subjects. At this time, in both groups of subjects, the levels of 15-keto-13,14-dihydro-prostaglandin F2alpha were lower than at rest. The level of noradrenaline observed following exercise were lower than during exercise in all but one subject. It would appear that neither noradrenaline nor prostaglandin F2alpha (or its metabolites) play a significant role in the aetiology of exercise-induced asthma.", "contents": "Exercise-related changes in plasma levels of 15-keto-13,14-dihydro-prostaglandin F2alpha and noradrenaline in asthmatic and normal subjects. In an attempt to elucidate the roles of prostaglandin F2alpha and noradrenaline in exercise-induced asthma, plasma levels of these substances were measured at rest, during and after exercise in normal and asthmatic subjects. Changes in airways resistance were assessed by measuring the peak expiratory flow rate. Plasma levels of 15-keto-13,14-dihydro-prostaglandin F2alpha (a relatively stable metabolite of prostaglandin F2alpha) and noradrenaline, at rest, and the changes that occurred during and after exercise, were similar in both the normal and asthmatic subjects. Exercise-induced broncho-constriction occurred in all asthmatic subjects following exercise while no significant change occurred in the peak expiratory flow rates of the normal subjects. At this time, in both groups of subjects, the levels of 15-keto-13,14-dihydro-prostaglandin F2alpha were lower than at rest. The level of noradrenaline observed following exercise were lower than during exercise in all but one subject. It would appear that neither noradrenaline nor prostaglandin F2alpha (or its metabolites) play a significant role in the aetiology of exercise-induced asthma."} {"id": "PMID:1273544", "title": "On the pharmacokinetics of rifampicin during treatment with intermittent administration. II. Influence of age and sex and of the patients.", "content": "Pharmacokinetic investigations in 75 patients receiving their first treatment for infectious lung tuberculosis gave the following results: RMP and its products of biotransformation are excreted via the urine in smaller amounts in patients above 55 years than in younger patients. In the older age group the induction phase - as measured by the urinary excretion of RMP - is also more marked than in younger patients. Both the serum RMP-concentration and the urinary excretion of RMP are significantly higher in women than in men. The sex specific differences in pharacokinetics seem to be of clinical importance. Because of the higher serum RMP-concentration it is possible to reduce the RMP-dosage 10% in female patients, even with intermittent administration, and to diminish the risk of dose-dependent side effects.", "contents": "On the pharmacokinetics of rifampicin during treatment with intermittent administration. II. Influence of age and sex and of the patients. Pharmacokinetic investigations in 75 patients receiving their first treatment for infectious lung tuberculosis gave the following results: RMP and its products of biotransformation are excreted via the urine in smaller amounts in patients above 55 years than in younger patients. In the older age group the induction phase - as measured by the urinary excretion of RMP - is also more marked than in younger patients. Both the serum RMP-concentration and the urinary excretion of RMP are significantly higher in women than in men. The sex specific differences in pharacokinetics seem to be of clinical importance. Because of the higher serum RMP-concentration it is possible to reduce the RMP-dosage 10% in female patients, even with intermittent administration, and to diminish the risk of dose-dependent side effects."} {"id": "PMID:1273545", "title": "Increase in years of life after eliminating causes of death: significance for health priorities.", "content": "The theory of competing risks of death has been applied in this study for the construction of two indices: (1) increase in the expectation of life as a function of age, and (2) increase in the average number of years to be lived by a newborn up to various ages, when selected causes of death are eliminated. The indices have been applied to the 1970 mortality in Finland. Vascular diseases comprise the most important cause of death in both sexes, when the first index is applied. According to the second index, considering ages up to 65 years, violent deaths emerge as the most important cause of death among men and neoplasms appear equally important as vascular diseases among women. The magnitude of a health problem was found to be dependent on the index selected, which should be considered in health planning.", "contents": "Increase in years of life after eliminating causes of death: significance for health priorities. The theory of competing risks of death has been applied in this study for the construction of two indices: (1) increase in the expectation of life as a function of age, and (2) increase in the average number of years to be lived by a newborn up to various ages, when selected causes of death are eliminated. The indices have been applied to the 1970 mortality in Finland. Vascular diseases comprise the most important cause of death in both sexes, when the first index is applied. According to the second index, considering ages up to 65 years, violent deaths emerge as the most important cause of death among men and neoplasms appear equally important as vascular diseases among women. The magnitude of a health problem was found to be dependent on the index selected, which should be considered in health planning."} {"id": "PMID:1273546", "title": "Hospital treatment of addicts arrested for intoxication in Finland.", "content": "In the present study the treatment of addicts as performed by the Finnish police was investigated. The intention was to evaluate how the treatment procedure functioned in meeting the need for medical care and safety of the addict. The series was collected from the police district of Helsinki, the Finnish capital, and comprised all addicts arrested and transported to hospital during 1969. The series totalled 859 cases, which is about 2% of all addicts arrested in Helsinki during 1969. The reasons for transportation to hospital were: external injuries (60%) and the addict's complaints of an injury or illness (17%). Of all subjects, 44 were admitted to a hospital ward and of these, 2 died later on the ward. Furthermore, 7 addicts had died at the police station, on the way to hospital, or at the out-patients' department. Thus the number of deaths totalled 9. On investigating the cases of death in detail it was found that omission of or delay in the transport to hospital may have been of decisive influence on the addict's death in 4 cases. It was estimated that, had the police not transported any of the addicts to hospital, the number of deaths would have been about 20. When the cost of hospital treatment and transport to hospital is used as an evaluation factor the effort of the activity covered by the present study is 98 500 Fmk (U.S. $ 23 200). The output is the number of lives saved, i.e. 11. The efficiency of the activity is thus the saving of one life at the cost of about 9000 Fmk (about 2 100 U.S. $). The social characteristics of the addict were not found to have had a decisive bearing on the question of transportation to hospital. Differences between the various points of activity were observed in the relative numbers of the addicts arrested and transported to hospital.", "contents": "Hospital treatment of addicts arrested for intoxication in Finland. In the present study the treatment of addicts as performed by the Finnish police was investigated. The intention was to evaluate how the treatment procedure functioned in meeting the need for medical care and safety of the addict. The series was collected from the police district of Helsinki, the Finnish capital, and comprised all addicts arrested and transported to hospital during 1969. The series totalled 859 cases, which is about 2% of all addicts arrested in Helsinki during 1969. The reasons for transportation to hospital were: external injuries (60%) and the addict's complaints of an injury or illness (17%). Of all subjects, 44 were admitted to a hospital ward and of these, 2 died later on the ward. Furthermore, 7 addicts had died at the police station, on the way to hospital, or at the out-patients' department. Thus the number of deaths totalled 9. On investigating the cases of death in detail it was found that omission of or delay in the transport to hospital may have been of decisive influence on the addict's death in 4 cases. It was estimated that, had the police not transported any of the addicts to hospital, the number of deaths would have been about 20. When the cost of hospital treatment and transport to hospital is used as an evaluation factor the effort of the activity covered by the present study is 98 500 Fmk (U.S. $ 23 200). The output is the number of lives saved, i.e. 11. The efficiency of the activity is thus the saving of one life at the cost of about 9000 Fmk (about 2 100 U.S. $). The social characteristics of the addict were not found to have had a decisive bearing on the question of transportation to hospital. Differences between the various points of activity were observed in the relative numbers of the addicts arrested and transported to hospital."} {"id": "PMID:1273547", "title": "Smoking and the subjective health condition among Finnish military conscripts.", "content": "Information on smoking habits and a subjective self-estimate of general state of health was collected by means of a questionnaire from 400 conscripts in Northern Finland. The data were treated by factor analysis. Long-term fatigue, frequent headache, insomnia and occasional depression were less frequent among non-smokers than among smokers.", "contents": "Smoking and the subjective health condition among Finnish military conscripts. Information on smoking habits and a subjective self-estimate of general state of health was collected by means of a questionnaire from 400 conscripts in Northern Finland. The data were treated by factor analysis. Long-term fatigue, frequent headache, insomnia and occasional depression were less frequent among non-smokers than among smokers."} {"id": "PMID:1273548", "title": "Results of a quit-smoking research project in a randomly selected population.", "content": "In the spring of 1973, 58 strictly randomized heavy smokers from a defined population of men born in 1914 were asked to quit smoking, at least for 8-9 weeks, as a part of a research project focused upon the relationship between smoking and peripheral blood flow, fibrinolysis, and lung function. Eighty-eight per cent of the smokers were willing to try to quit smoking. Seven (12%) refused at the outset, as they regarded quitting as impossible. Of the remaining 51 it was possible to keep 31 (60%) free from smoking for 8-9 weeks with the aid of an intense anti-smoking program lasting 6 weeks. Checks of continued smoking abstention were made by questionnaire and COHb-determination. After six weeks, no further information was given to the subjects. A follow-up after 8-9 months revealed that 33% of the 51 participants (i.e. 29% of the original 58) were still non-smokers. The long-lasting effect of our quit-smoking method was equal to the best reported by others and 30% is probably the highest rate of long-term success to be achieved in smoking cessation.", "contents": "Results of a quit-smoking research project in a randomly selected population. In the spring of 1973, 58 strictly randomized heavy smokers from a defined population of men born in 1914 were asked to quit smoking, at least for 8-9 weeks, as a part of a research project focused upon the relationship between smoking and peripheral blood flow, fibrinolysis, and lung function. Eighty-eight per cent of the smokers were willing to try to quit smoking. Seven (12%) refused at the outset, as they regarded quitting as impossible. Of the remaining 51 it was possible to keep 31 (60%) free from smoking for 8-9 weeks with the aid of an intense anti-smoking program lasting 6 weeks. Checks of continued smoking abstention were made by questionnaire and COHb-determination. After six weeks, no further information was given to the subjects. A follow-up after 8-9 months revealed that 33% of the 51 participants (i.e. 29% of the original 58) were still non-smokers. The long-lasting effect of our quit-smoking method was equal to the best reported by others and 30% is probably the highest rate of long-term success to be achieved in smoking cessation."} {"id": "PMID:1273549", "title": "The layman's medical vocabulary. A study of illness definitions and perceived need for medical care.", "content": "A knowledge of the layman's illness concepts is of value both for diagnosis and therapy in the practical application of the medical services. It is also valuable for the estimation of morbidity and of the need for medical assistance. The present article describes an investigation intended to throw light on the import of ten different illness concepts and on the implications these may have for the utilization of the medical services. The study is based on interviews with 100 middle-aged women. Most of the respondents considered that an illness may have many causes--a multifactorial aetiology. Great differences between the illnesses were noted with respect to the opinions as to whether examination by a doctor was necessary for diagnosis. The interpretations as to whether an illness needed treatment--medical attention, medicine, hospital care--seemed however to be more closely related to its duration than to its nature. A long duration was regarded by a surprisingly large number as a sign that hospitalization was required--even in the case of a common cold! Only 8% considered obesity 'serious'. As regards the choice of illness alternatives, earlier experience of illness influenced this only in the case of 'shortness of breath' and 'nervous symptoms'. Social class was not found to affect the type of answer.", "contents": "The layman's medical vocabulary. A study of illness definitions and perceived need for medical care. A knowledge of the layman's illness concepts is of value both for diagnosis and therapy in the practical application of the medical services. It is also valuable for the estimation of morbidity and of the need for medical assistance. The present article describes an investigation intended to throw light on the import of ten different illness concepts and on the implications these may have for the utilization of the medical services. The study is based on interviews with 100 middle-aged women. Most of the respondents considered that an illness may have many causes--a multifactorial aetiology. Great differences between the illnesses were noted with respect to the opinions as to whether examination by a doctor was necessary for diagnosis. The interpretations as to whether an illness needed treatment--medical attention, medicine, hospital care--seemed however to be more closely related to its duration than to its nature. A long duration was regarded by a surprisingly large number as a sign that hospitalization was required--even in the case of a common cold! Only 8% considered obesity 'serious'. As regards the choice of illness alternatives, earlier experience of illness influenced this only in the case of 'shortness of breath' and 'nervous symptoms'. Social class was not found to affect the type of answer."} {"id": "PMID:1273550", "title": "Sexual problems in patients suffering from multiple sclerosis.", "content": "A questionnaire which allowed anonymous answering and which also included many other questions besides those dealing with sexual life was sent to 302 patients suffering from multiple sclerosis (MS). Sexual life had changed for 91% of males and 72% of females. About half of the patients replied that their sexual life was unsatisfactory or had ceased altogether. These patients were as a rule in a relative poor physical condition. In males, disturbances in erection (62%) were the most common problem, erection was normal in only 20%. In females the essential figures were: loss of orgasm in 33%, loss of libido in 27% and spasticity in 12%. There was no correlation between the incidence of sexual disturbances and the duration of the MS. It seems that the neurological disturbances in sexual life depend simply on the location of the plaques in the central nervous system.", "contents": "Sexual problems in patients suffering from multiple sclerosis. A questionnaire which allowed anonymous answering and which also included many other questions besides those dealing with sexual life was sent to 302 patients suffering from multiple sclerosis (MS). Sexual life had changed for 91% of males and 72% of females. About half of the patients replied that their sexual life was unsatisfactory or had ceased altogether. These patients were as a rule in a relative poor physical condition. In males, disturbances in erection (62%) were the most common problem, erection was normal in only 20%. In females the essential figures were: loss of orgasm in 33%, loss of libido in 27% and spasticity in 12%. There was no correlation between the incidence of sexual disturbances and the duration of the MS. It seems that the neurological disturbances in sexual life depend simply on the location of the plaques in the central nervous system."} {"id": "PMID:1273551", "title": "Mental health and housing.", "content": "With the present trend away from the designing of individual buildings and towards the systematic planning of whole residential communities, it should be possible to take mental health requirements into account at the planning stage. At present, sociologists are all too seldom consulted on matters of residential planning. When discussing the relationship between housing and mental health one cannot restrict oneself only to the external aspects of the house, but rather one must also consider the opportunities available for the members of the family to satisfy their own needs, both within the home and in its immediate surroundings. Factors which may affect residential requirements include geographical location, type and standard of dwelling and time and continuity of occupation. A move between two districts or groups representing different housing norms and values may lead to withdrawal symptoms in the individual. This may arise equally well from the remoteness of the country districts as from the conflicting pressures brought on by the abundance of contacts available in the large towns. Town life tends to heighten susceptibility to neuroses and personality conflicts. The character of a residential area may affect the mental health of its occupants. Faris & Dunham (4), in studying the incidence of various types of mental illness with an urban population, observed that schizophrenia was most common among people who were in some way isolated from social involvement. The striving for spaciousness in residential areas and the creation of a \"summer city\" or \"garden city\" image or a \"family-centred way of life\" may lead to unexpected problems and have a variety of social consequences. Mental health difficulties have been noted, for example, among housewives in \"dormitory\" towns or suburbs (11). The institutions required by a community may be grouped into four categories, representing the basic needs of its members. These are (1) economic institutions, (2) social and political organizations, (3) leisure-time clubs and (4) societies and institutions for promoting social integration, including educational, advisory and assistance bodies. The study of satiation processes offers an interesting approach to the relationship between housing and mental health. Man requires new stimuli to motivate him. Boredom and satiation serve to induce passivity and may provoke destructive behaviour and escapism. Finland has the highest percentage of dwellings constructed in the immediate post-war period of any country in Europe, and in respect of the functions of housing many aspects are still apparent which are detrimental to mental health.", "contents": "Mental health and housing. With the present trend away from the designing of individual buildings and towards the systematic planning of whole residential communities, it should be possible to take mental health requirements into account at the planning stage. At present, sociologists are all too seldom consulted on matters of residential planning. When discussing the relationship between housing and mental health one cannot restrict oneself only to the external aspects of the house, but rather one must also consider the opportunities available for the members of the family to satisfy their own needs, both within the home and in its immediate surroundings. Factors which may affect residential requirements include geographical location, type and standard of dwelling and time and continuity of occupation. A move between two districts or groups representing different housing norms and values may lead to withdrawal symptoms in the individual. This may arise equally well from the remoteness of the country districts as from the conflicting pressures brought on by the abundance of contacts available in the large towns. Town life tends to heighten susceptibility to neuroses and personality conflicts. The character of a residential area may affect the mental health of its occupants. Faris & Dunham (4), in studying the incidence of various types of mental illness with an urban population, observed that schizophrenia was most common among people who were in some way isolated from social involvement. The striving for spaciousness in residential areas and the creation of a \"summer city\" or \"garden city\" image or a \"family-centred way of life\" may lead to unexpected problems and have a variety of social consequences. Mental health difficulties have been noted, for example, among housewives in \"dormitory\" towns or suburbs (11). The institutions required by a community may be grouped into four categories, representing the basic needs of its members. These are (1) economic institutions, (2) social and political organizations, (3) leisure-time clubs and (4) societies and institutions for promoting social integration, including educational, advisory and assistance bodies. The study of satiation processes offers an interesting approach to the relationship between housing and mental health. Man requires new stimuli to motivate him. Boredom and satiation serve to induce passivity and may provoke destructive behaviour and escapism. Finland has the highest percentage of dwellings constructed in the immediate post-war period of any country in Europe, and in respect of the functions of housing many aspects are still apparent which are detrimental to mental health."} {"id": "PMID:1273552", "title": "Do you die from rheumatism? The five-year mortality in a middle-aged population sample with respect to reported joint symptoms.", "content": "With special reference to reported joint symptoms, the five-year mortality was studied of a population sample of 3394 persons, 56-60 years old in 1965. An age- and sex-matched comparison was made between the mortality of the total population of the same age-group, and the sample investigated. A significant excess mortality was found for males reporting previous hospital admission for \"rheumatoid arthritis\". In this group, however, only 28% really had rheumatoid arthritis according to generally used criteria. The other diseases were mainly previous rheumatic fever and degenerative joint disease. It is concluded that males are harder hit by degenerative joint disease than females. The sample investigated had a lower mortality than the population from which it was sampled. The comparability of a fixed sample and a mean population found in official statistics is discussed. The non-response group was estimated to have a considerable excess mortality.", "contents": "Do you die from rheumatism? The five-year mortality in a middle-aged population sample with respect to reported joint symptoms. With special reference to reported joint symptoms, the five-year mortality was studied of a population sample of 3394 persons, 56-60 years old in 1965. An age- and sex-matched comparison was made between the mortality of the total population of the same age-group, and the sample investigated. A significant excess mortality was found for males reporting previous hospital admission for \"rheumatoid arthritis\". In this group, however, only 28% really had rheumatoid arthritis according to generally used criteria. The other diseases were mainly previous rheumatic fever and degenerative joint disease. It is concluded that males are harder hit by degenerative joint disease than females. The sample investigated had a lower mortality than the population from which it was sampled. The comparability of a fixed sample and a mean population found in official statistics is discussed. The non-response group was estimated to have a considerable excess mortality."} {"id": "PMID:1273553", "title": "Coronary ostial stenosis: a complication of aortic valve replacement of coronary perfusion.", "content": "Coronary ostial stenosis developing after aortic valve replacement is a clinically well-recognized entity. This non-atheromatous intimal proliferation may be limited to the proximal part of the coronary artery, probably as a complication of intra-operative coronary perfusion. It may also occur in association with widespread intimal thickening in the aortic root, presumedly as a reaction to turbulence around aortic ball valve prostheses. We have encountered this process in 2/508 patients (0.4%), who underwent aortic valve replacement with the Bj\u00f6rk-Shiley tilting disc valve prosthesis. The coronary perfusion technique was identical in all the operations.", "contents": "Coronary ostial stenosis: a complication of aortic valve replacement of coronary perfusion. Coronary ostial stenosis developing after aortic valve replacement is a clinically well-recognized entity. This non-atheromatous intimal proliferation may be limited to the proximal part of the coronary artery, probably as a complication of intra-operative coronary perfusion. It may also occur in association with widespread intimal thickening in the aortic root, presumedly as a reaction to turbulence around aortic ball valve prostheses. We have encountered this process in 2/508 patients (0.4%), who underwent aortic valve replacement with the Bj\u00f6rk-Shiley tilting disc valve prosthesis. The coronary perfusion technique was identical in all the operations."} {"id": "PMID:1273554", "title": "Recurrent cardiac tamponade after replacement of three heart valves. A case report.", "content": "Delayed pericardial effusion and cardiac tamponade are rare late complications of open-heart surgery. A case after replacement of all three heart valves with the Bj\u00f6rk-Shiley tilting disc valves with an unusual clinical course is presented in the following. Unsuccessful subsequent medical treatment, subsequent surgical intervention and its results are described and discussed. The need of further reports on similar observations is emphasized.", "contents": "Recurrent cardiac tamponade after replacement of three heart valves. A case report. Delayed pericardial effusion and cardiac tamponade are rare late complications of open-heart surgery. A case after replacement of all three heart valves with the Bj\u00f6rk-Shiley tilting disc valves with an unusual clinical course is presented in the following. Unsuccessful subsequent medical treatment, subsequent surgical intervention and its results are described and discussed. The need of further reports on similar observations is emphasized."} {"id": "PMID:1273555", "title": "Mitral valve replacement with ball and tilting disc valve prosthesis. A clinical and haemodynamic study.", "content": "A survey is presented on the results of 100 consecutive patients who underwent mitral valve (78 patients) or mitral and aortic and/or tricuspid valve replacement (22 patients) with ball or disc valve prosthesis. The patients were followed-up from 6 to 54 months postoperatively. The mortality for mitral valve replacement was 13 (17%) early deaths (up to one month from operation) and 5 (6%) late deaths. The corresponding figures for multiple valve replacements were 9 (41%) and 3 (14%). A direct correlation was found between early mortality and preoperative functional class IV of the New York Heart Association (30% dead). Pulmonary hypertension combined with multiple valve disease resulted in an early mortality of 42%. No significant differences in early mortality figures after MVR were found between ball and disc valve prostheses. Predominant complications were respiratory infection and atelectasis (13%), acute myocardial infarction (11%) and haemorrhage (9%). Haemolysis was found in 9 patients and three other patients had haemolytic anaemia attributable to paravalvular leak which in two indicated the reapplication of the prosthesis. The main causes of death were heart failure, 8 early and 4 late deaths, and myocardial infarction, 5 and 4 respectively.", "contents": "Mitral valve replacement with ball and tilting disc valve prosthesis. A clinical and haemodynamic study. A survey is presented on the results of 100 consecutive patients who underwent mitral valve (78 patients) or mitral and aortic and/or tricuspid valve replacement (22 patients) with ball or disc valve prosthesis. The patients were followed-up from 6 to 54 months postoperatively. The mortality for mitral valve replacement was 13 (17%) early deaths (up to one month from operation) and 5 (6%) late deaths. The corresponding figures for multiple valve replacements were 9 (41%) and 3 (14%). A direct correlation was found between early mortality and preoperative functional class IV of the New York Heart Association (30% dead). Pulmonary hypertension combined with multiple valve disease resulted in an early mortality of 42%. No significant differences in early mortality figures after MVR were found between ball and disc valve prostheses. Predominant complications were respiratory infection and atelectasis (13%), acute myocardial infarction (11%) and haemorrhage (9%). Haemolysis was found in 9 patients and three other patients had haemolytic anaemia attributable to paravalvular leak which in two indicated the reapplication of the prosthesis. The main causes of death were heart failure, 8 early and 4 late deaths, and myocardial infarction, 5 and 4 respectively."} {"id": "PMID:1273556", "title": "Surgery in acute and chronic pericarditis. Pathophysiology and management.", "content": "Forty-two cases of surgically treated pericarditis are presented, with comments on the management and pathophysiology of the acute, recurrent, and chronic stages of the disease. The spectrum of aetiological factors has changed within the last few decades in that tuberculosis is now rare, whereas uraemic pericarditis is referred to surgery with increasing frequency. With the advent of haemodialysis and renal transplantation, these cases should be treated vigorously, since they are amenable to surgical cure. Rapid surgical intervention is advocated in impending tamponade, and in all other acute cases which do not respond promptly to conservative management. In recurrent and chronic pericarditis, surgery is also preferable to long-term medical treatment with steroids and diuretics. Chronic pericarditis should not be allowed to progress to an advanced stage of disease with myocardial involvement and impairment of liver function. Early operation carries little hazard and gives lasting relief in the majority of cases. Microscopical examinations and laboratory analyses point towards an abnormal permeability of capillaries and visceral pericardium as an early and major event in the development of pericardial effusions. Destruction or preservation of the mesothelial cell lining is probably an important factor in determining the progression of acute disease towards adhesions and constriction.", "contents": "Surgery in acute and chronic pericarditis. Pathophysiology and management. Forty-two cases of surgically treated pericarditis are presented, with comments on the management and pathophysiology of the acute, recurrent, and chronic stages of the disease. The spectrum of aetiological factors has changed within the last few decades in that tuberculosis is now rare, whereas uraemic pericarditis is referred to surgery with increasing frequency. With the advent of haemodialysis and renal transplantation, these cases should be treated vigorously, since they are amenable to surgical cure. Rapid surgical intervention is advocated in impending tamponade, and in all other acute cases which do not respond promptly to conservative management. In recurrent and chronic pericarditis, surgery is also preferable to long-term medical treatment with steroids and diuretics. Chronic pericarditis should not be allowed to progress to an advanced stage of disease with myocardial involvement and impairment of liver function. Early operation carries little hazard and gives lasting relief in the majority of cases. Microscopical examinations and laboratory analyses point towards an abnormal permeability of capillaries and visceral pericardium as an early and major event in the development of pericardial effusions. Destruction or preservation of the mesothelial cell lining is probably an important factor in determining the progression of acute disease towards adhesions and constriction."} {"id": "PMID:1273557", "title": "Long-term observations of cardiac arrhythmias during and after cardiac surgery. I. Acquired heart disease.", "content": "Twelve arrhythmias that occurred during and following surgery for acquired heart disease were studied in a group of 52 randomly selected patients. In cases of aortic and mitral valve replacement, Bj\u00f6rk-Shiley prosthetic valves were used, and procain-magnesium-aspartate solution was applied for cardiac arrest. Registration and analysis of rhythm disturbances were carried out at 10 different time intervals, spaced narrowly in the intra-and early postoperative phases, then more widely up to the 96th hour of observation. Arrhythmic incidence and occurrence per case and phase are given, thereby allowing an account of transient arrhythmias as well. The peak occurrence of serious rhythm disturbance was found, intraoperatively, at about the time of aortic cross-clamping and release (ischaemic effect) with the exception of the mitral-commissurotomy group. The 1st-6th postbypass hours showed an arrhythmia trough, followed by a 2nd peak (9th-96th postoperative hour) made up of less serious arrhythmias (electrolyte- and acid-base disturbances; digitalis effects). All 12 arrhythmia types, as well as the five separately considered ventricular arrhythmias of the \"first arrhythmia peak\", did not reveal any significant relation to: patients' age, N.Y.H.A. criteria, pre-operative PAm or the duration of anaesthesia, surgery and bypass time.", "contents": "Long-term observations of cardiac arrhythmias during and after cardiac surgery. I. Acquired heart disease. Twelve arrhythmias that occurred during and following surgery for acquired heart disease were studied in a group of 52 randomly selected patients. In cases of aortic and mitral valve replacement, Bj\u00f6rk-Shiley prosthetic valves were used, and procain-magnesium-aspartate solution was applied for cardiac arrest. Registration and analysis of rhythm disturbances were carried out at 10 different time intervals, spaced narrowly in the intra-and early postoperative phases, then more widely up to the 96th hour of observation. Arrhythmic incidence and occurrence per case and phase are given, thereby allowing an account of transient arrhythmias as well. The peak occurrence of serious rhythm disturbance was found, intraoperatively, at about the time of aortic cross-clamping and release (ischaemic effect) with the exception of the mitral-commissurotomy group. The 1st-6th postbypass hours showed an arrhythmia trough, followed by a 2nd peak (9th-96th postoperative hour) made up of less serious arrhythmias (electrolyte- and acid-base disturbances; digitalis effects). All 12 arrhythmia types, as well as the five separately considered ventricular arrhythmias of the \"first arrhythmia peak\", did not reveal any significant relation to: patients' age, N.Y.H.A. criteria, pre-operative PAm or the duration of anaesthesia, surgery and bypass time."} {"id": "PMID:1273558", "title": "Pulmonary vein flow pattern in mitral incompetence, combined mitral stenosis/incompetence and after prosthetic valve replacement.", "content": "Pulmonary vein flow (PVF) pattern was studied with an electromagnetic flowmeter in 11 patients with combined mitral stenosis/incompetence (MS/MI), in 6 patients with pure mitral incompetence (MI) and in 24 patients after mitral valve replacement (MVR). ECG, left atrial and left ventricular pressures were recorded simultaneously. The anomalous flow patterns, which were recorded, reflected the left atrial events and mitral valve function. Before MVR, the major forward flow occurred in ventricular diastole. In patients with predominating MS and small/moderate MI, a small retrograde PVF (RF) occurred in early ventricular systole, while pure or combined severe MI produced a holosystolic reversal of PVF.", "contents": "Pulmonary vein flow pattern in mitral incompetence, combined mitral stenosis/incompetence and after prosthetic valve replacement. Pulmonary vein flow (PVF) pattern was studied with an electromagnetic flowmeter in 11 patients with combined mitral stenosis/incompetence (MS/MI), in 6 patients with pure mitral incompetence (MI) and in 24 patients after mitral valve replacement (MVR). ECG, left atrial and left ventricular pressures were recorded simultaneously. The anomalous flow patterns, which were recorded, reflected the left atrial events and mitral valve function. Before MVR, the major forward flow occurred in ventricular diastole. In patients with predominating MS and small/moderate MI, a small retrograde PVF (RF) occurred in early ventricular systole, while pure or combined severe MI produced a holosystolic reversal of PVF."} {"id": "PMID:1273559", "title": "Pulmonary vein flow pattern in mitral stenosis before and after commissurotomy.", "content": "Pulmonary vein flow (PVF) pattern was studied with an electromagnetic flowmeter in 15 patients with mitral stenosis. ECG, left atrial and left ventricular pressure were recorded simultaneously. Commissurotomy was performed in 8 patients and prosthetic valve replacement in the others. Measurements were performed before and after the intracardiac procedure. The predominating forward flow occurred in ventricular diastole, in contrast to ventricular systole in normal hearts. A small retrograde PVF was observed in 11/15 patients in early ventricular systole, coinciding with the c-wave in left atrial pressure (LAP). The reversed flow did not exceed 13% and showed no correlation to a slight regurgitation demonstrated at left ventricular angiography. The maximum delay in forward systolic PVF after onset of ventricular systole was 0.10 sec. The PVF pattern remained unchanged after commissurotomy in the majority of patients, even after reduction of the mitral valve gradient to less than 5 mmHg. However, holosystolic reversed PVF occurred in one patient, indicating a severe mitral regurgitation. The method of PVF recording is simple and proved useful for haemodynamic analysis and as a control after mitral valve surgery for evaluating the degree of mitral regurgitation.", "contents": "Pulmonary vein flow pattern in mitral stenosis before and after commissurotomy. Pulmonary vein flow (PVF) pattern was studied with an electromagnetic flowmeter in 15 patients with mitral stenosis. ECG, left atrial and left ventricular pressure were recorded simultaneously. Commissurotomy was performed in 8 patients and prosthetic valve replacement in the others. Measurements were performed before and after the intracardiac procedure. The predominating forward flow occurred in ventricular diastole, in contrast to ventricular systole in normal hearts. A small retrograde PVF was observed in 11/15 patients in early ventricular systole, coinciding with the c-wave in left atrial pressure (LAP). The reversed flow did not exceed 13% and showed no correlation to a slight regurgitation demonstrated at left ventricular angiography. The maximum delay in forward systolic PVF after onset of ventricular systole was 0.10 sec. The PVF pattern remained unchanged after commissurotomy in the majority of patients, even after reduction of the mitral valve gradient to less than 5 mmHg. However, holosystolic reversed PVF occurred in one patient, indicating a severe mitral regurgitation. The method of PVF recording is simple and proved useful for haemodynamic analysis and as a control after mitral valve surgery for evaluating the degree of mitral regurgitation."} {"id": "PMID:1273560", "title": "Intra-operative haemodynamic findings and their prognostic significance in femoropopliteal reversed saphenous vein graft bypass operations.", "content": "Post-reconstructive graft blood flow (basal flow') was measured by means of an electromagnetic flowmeter in 72 consecutive femoropopliteal reversed saphenous vein grafts performed for occlusive atherosclerosis causing leg ischaemia. In the last 48 operations, post-reconstructive pre- and post-graft intra-arterial pressures were recorded, and graft blood flow after papavarine-induced vasodilation ('maximal flow') was measured. Mean 'basal flow' was 132 ml/min, mean 'maximal flow' 285 ml/min and mean flow increment after papavarin 136%. Mean 'basal flow', mean 'maximal flow' and mean flow increment after papavarine were higher in the claudication group than in the gangrene group, and higher in cases having good angiographic run-off than in those having poor. Mean common femoral and popliteal pressures were 85 and 80 mmHg, with no differences between different groups. Mean post-reconstructive graft pressure gradient was 5.1 mm. Mean peripheral resistance was 769 milliprus, being higher in the gangrene group and in cases having poor run-off. The prognostic significance of these findings was evaluated by analysing patency in all patients living 3 months ('early') and 1 year ('late') after operation. Cases having a 'basal flow' less than 60 ml/min, a 'maximal flow' less than 200 ml/min or a flow increment after papavarine less than 100% had significantly poorer 'early' patency (p less than 0.01) and 'late' patency (p less than 0.05). Femoral and popliteal pressures, graft pressure gradients and peripheral resistance did not influence patency significantly.", "contents": "Intra-operative haemodynamic findings and their prognostic significance in femoropopliteal reversed saphenous vein graft bypass operations. Post-reconstructive graft blood flow (basal flow') was measured by means of an electromagnetic flowmeter in 72 consecutive femoropopliteal reversed saphenous vein grafts performed for occlusive atherosclerosis causing leg ischaemia. In the last 48 operations, post-reconstructive pre- and post-graft intra-arterial pressures were recorded, and graft blood flow after papavarine-induced vasodilation ('maximal flow') was measured. Mean 'basal flow' was 132 ml/min, mean 'maximal flow' 285 ml/min and mean flow increment after papavarin 136%. Mean 'basal flow', mean 'maximal flow' and mean flow increment after papavarine were higher in the claudication group than in the gangrene group, and higher in cases having good angiographic run-off than in those having poor. Mean common femoral and popliteal pressures were 85 and 80 mmHg, with no differences between different groups. Mean post-reconstructive graft pressure gradient was 5.1 mm. Mean peripheral resistance was 769 milliprus, being higher in the gangrene group and in cases having poor run-off. The prognostic significance of these findings was evaluated by analysing patency in all patients living 3 months ('early') and 1 year ('late') after operation. Cases having a 'basal flow' less than 60 ml/min, a 'maximal flow' less than 200 ml/min or a flow increment after papavarine less than 100% had significantly poorer 'early' patency (p less than 0.01) and 'late' patency (p less than 0.05). Femoral and popliteal pressures, graft pressure gradients and peripheral resistance did not influence patency significantly."} {"id": "PMID:1273562", "title": "Regional cerebral blood flow and vertebral angiography at rest and in connection with arm work in patients with the \"subclavian steal phenomenon\".", "content": "Vascular anatomy and haemodynamics of the vertebro-basilar system were investigated by means of vertebral angiography as well as rCBF measurements using the 133Xenon clearance method in 12 patients with occlusive disease of the subclavian artery. Prior to the investigation, the occlusive lesions had been demonstrated by aortocervical angiography, which in 9 out of 12 patients showed reversed vertebral blood flow at rest. All selective vertebral angiographies and rCBF measurements were performed at rest and in connection with graded arm exercise. Patients with the subclavian steal phenomenon were found to have a slightly reduced rCBF. After arm exercise, the intracranial flow velocity of contrast medium in the cerebral vessels remained unchanged, while the velocity of the reversed flow of contrast medium in the vertebral artery was increased. Regional cerebral blood flow in the vertebro-basilar system increased during arm exercise, the average increase being about 16%. The augmentation of flow is probably due to activation of neuronal processes within the brain. The magnitude of these flow alterations in healthy individuals is unknown.", "contents": "Regional cerebral blood flow and vertebral angiography at rest and in connection with arm work in patients with the \"subclavian steal phenomenon\". Vascular anatomy and haemodynamics of the vertebro-basilar system were investigated by means of vertebral angiography as well as rCBF measurements using the 133Xenon clearance method in 12 patients with occlusive disease of the subclavian artery. Prior to the investigation, the occlusive lesions had been demonstrated by aortocervical angiography, which in 9 out of 12 patients showed reversed vertebral blood flow at rest. All selective vertebral angiographies and rCBF measurements were performed at rest and in connection with graded arm exercise. Patients with the subclavian steal phenomenon were found to have a slightly reduced rCBF. After arm exercise, the intracranial flow velocity of contrast medium in the cerebral vessels remained unchanged, while the velocity of the reversed flow of contrast medium in the vertebral artery was increased. Regional cerebral blood flow in the vertebro-basilar system increased during arm exercise, the average increase being about 16%. The augmentation of flow is probably due to activation of neuronal processes within the brain. The magnitude of these flow alterations in healthy individuals is unknown."} {"id": "PMID:1273563", "title": "A case-referent study on neuropsychiatric disorders among workers exposed to solvents.", "content": "Published reports give justification for the belief that long-term exposure to solvents might induce chronic but nonspecific neuropsychiatric conditions. This case-referent study of data from a regional Swedish pension fund register indicated a risk ration of 1.8 in regard to nonspecific neuropsychiatric disorders among workers such as painters, varnishers and carpetlayers who are exposed to solvents as compared to workers not so exposed. Moreover a dose-response relationship seems to exist between exposure in terms of occupational years and neuropsychiatric conditions, the result being that persons affected are considered eligible for disability pensions.", "contents": "A case-referent study on neuropsychiatric disorders among workers exposed to solvents. Published reports give justification for the belief that long-term exposure to solvents might induce chronic but nonspecific neuropsychiatric conditions. This case-referent study of data from a regional Swedish pension fund register indicated a risk ration of 1.8 in regard to nonspecific neuropsychiatric disorders among workers such as painters, varnishers and carpetlayers who are exposed to solvents as compared to workers not so exposed. Moreover a dose-response relationship seems to exist between exposure in terms of occupational years and neuropsychiatric conditions, the result being that persons affected are considered eligible for disability pensions."} {"id": "PMID:1273564", "title": "Urinary mandelic acid concentration after occupational exposure to styrene and its use as a biological exposure test.", "content": "Excretion of mandelic acid from workers in the reinforced polyester plastic industry was studied with the determination of urinary mandelic acid concentrations. The styrene exposure level at the workplaces was evaluated with measurements of the styrene concentration in the ambient air. Three different groups (I, II and III) were studied. In group I [n=9, median of the time-weighted average (TWA) of exposure = 23 ppmof styrene, postexposure observation period = 64 h] two excretion slopes were observed, the first with a median half-time of 9.4 h (postexposure period 0--18 h) and a second with a median half-time of 16.6 h (postexposure period 19--64 h). For group II (n=9, median TWA exposure = 248 ppm, postexposure observation period = 15 h) a half-time of 6.4 h was found. These results suggest that the excretion rate of mandelic acid is dependent on the styrene exposure level. In addition the mandelic acid concentrations of 29 workers (group III) before and after the work shift were analyzed. The urinary mandelic acid concentrations of groups I, II and III, sampled immediately after the 8-h work shift, correlated with the 8-h TWA of styrene exposure (n=47, r=0.93). Accordingly about 2,300 mg of mandelic acid per gram of creatinine corresponded to 100 ppm of styrene.", "contents": "Urinary mandelic acid concentration after occupational exposure to styrene and its use as a biological exposure test. Excretion of mandelic acid from workers in the reinforced polyester plastic industry was studied with the determination of urinary mandelic acid concentrations. The styrene exposure level at the workplaces was evaluated with measurements of the styrene concentration in the ambient air. Three different groups (I, II and III) were studied. In group I [n=9, median of the time-weighted average (TWA) of exposure = 23 ppmof styrene, postexposure observation period = 64 h] two excretion slopes were observed, the first with a median half-time of 9.4 h (postexposure period 0--18 h) and a second with a median half-time of 16.6 h (postexposure period 19--64 h). For group II (n=9, median TWA exposure = 248 ppm, postexposure observation period = 15 h) a half-time of 6.4 h was found. These results suggest that the excretion rate of mandelic acid is dependent on the styrene exposure level. In addition the mandelic acid concentrations of 29 workers (group III) before and after the work shift were analyzed. The urinary mandelic acid concentrations of groups I, II and III, sampled immediately after the 8-h work shift, correlated with the 8-h TWA of styrene exposure (n=47, r=0.93). Accordingly about 2,300 mg of mandelic acid per gram of creatinine corresponded to 100 ppm of styrene."} {"id": "PMID:1273565", "title": "Eight-year follow-up of viscose rayon workers exposed to carbon disulfide.", "content": "An 8-year follow-up of workers exposed for at least 5 years to carbon disulfide showed an excess of deaths due to coronary heart disease in reference to a comparison cohort. However, after effective preventive measures, e.g., leaving only 19% of the original group exposed and reducing the level of exposure to less than 10 ppm, had been undertaken after the 5th year of follow-up, coronary mortality decreased and no excess mortality during the last 3 years of follow-up occurred. These results, although only suggestive -- due to the small number of deaths and the short time of follow-up after the intervention -- seem promising from the point of view of improving the prognosis of workers who have already accumulated an excess risk for coronary death.", "contents": "Eight-year follow-up of viscose rayon workers exposed to carbon disulfide. An 8-year follow-up of workers exposed for at least 5 years to carbon disulfide showed an excess of deaths due to coronary heart disease in reference to a comparison cohort. However, after effective preventive measures, e.g., leaving only 19% of the original group exposed and reducing the level of exposure to less than 10 ppm, had been undertaken after the 5th year of follow-up, coronary mortality decreased and no excess mortality during the last 3 years of follow-up occurred. These results, although only suggestive -- due to the small number of deaths and the short time of follow-up after the intervention -- seem promising from the point of view of improving the prognosis of workers who have already accumulated an excess risk for coronary death."} {"id": "PMID:1273566", "title": "Occupational lead exposure in Finland. V. Shipyards and shipbreaking.", "content": "Three Finnish shipyards and two shipbreaking enterprises were studied for lead exposure. Blood lead (Pb-B) concentration was measured for 568 workers in the shipyards and 13 workers in the shipbreaking enterprises. Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity was determined for 139 workers in one shipyard and 7 workers in one shipbreaking enterprise. Hemoglobin level was determined for 545 workers in the three shipyards and 7 workers in one shipbreaking enterprise. Lead exposure in the shipyards was relatively low. No Pb-B value exceeded 70mug/100 ml. The most exposed occupations were welders, plumbers, painters, repairmen, and sheet metal workers. The mean Pb-B did not exceed 40 mug/100 ml in any of these groups. In both shipbreaking enterprises one Pb-B value exceeded 70 mug/100 ml, the mean Pb-B values of all the workers in the two enterprises being 51 and 46 mug/100 ml. respectively. ALAD values corresponded well with the respective Pb-B values. All the hemoglobin mean values were normal, and there were no statistically significant differences between the hemoglobin values of different groups.", "contents": "Occupational lead exposure in Finland. V. Shipyards and shipbreaking. Three Finnish shipyards and two shipbreaking enterprises were studied for lead exposure. Blood lead (Pb-B) concentration was measured for 568 workers in the shipyards and 13 workers in the shipbreaking enterprises. Erythrocyte delta-aminolevulinic acid dehydratase (ALAD) activity was determined for 139 workers in one shipyard and 7 workers in one shipbreaking enterprise. Hemoglobin level was determined for 545 workers in the three shipyards and 7 workers in one shipbreaking enterprise. Lead exposure in the shipyards was relatively low. No Pb-B value exceeded 70mug/100 ml. The most exposed occupations were welders, plumbers, painters, repairmen, and sheet metal workers. The mean Pb-B did not exceed 40 mug/100 ml in any of these groups. In both shipbreaking enterprises one Pb-B value exceeded 70 mug/100 ml, the mean Pb-B values of all the workers in the two enterprises being 51 and 46 mug/100 ml. respectively. ALAD values corresponded well with the respective Pb-B values. All the hemoglobin mean values were normal, and there were no statistically significant differences between the hemoglobin values of different groups."} {"id": "PMID:1273573", "title": "Gnathotrichus sulcatus: synergistic response to enantiomers of the aggregation pheromone sulcatol.", "content": "In laboratory and field bioassays, Gnathotrichus sulcatus responded to sulcatol (6-methyl-5-hepten-2-ol) only when both enantiomers were present. Response was greater to racemic sulcatol than to a mixture (65 : 35) of S-(+) and R-(-) enantiomers, the naturally occurring isomeric ratio. Enantiomer-specific active sites on receptor proteins in the same or different cells are implicated.", "contents": "Gnathotrichus sulcatus: synergistic response to enantiomers of the aggregation pheromone sulcatol. In laboratory and field bioassays, Gnathotrichus sulcatus responded to sulcatol (6-methyl-5-hepten-2-ol) only when both enantiomers were present. Response was greater to racemic sulcatol than to a mixture (65 : 35) of S-(+) and R-(-) enantiomers, the naturally occurring isomeric ratio. Enantiomer-specific active sites on receptor proteins in the same or different cells are implicated."} {"id": "PMID:1273571", "title": "The quantitative relations between diffusion-controlled reaction rate and characteristic parameters in enzyme-substrate reaction systems. I. Neutral substrates.", "content": "With the development of techniques for studying fast reactions, we are confronted with some experimental observations which, according to the classical diffusion-controlled reaction theory based on the assumption of pherical symmetry, will lead to paradoxical consequences. Recently, some investigators have attempted to present a theory of non-spherically symmetric diffusion-controlled reaction. Owing to the difficulty in mathematics, only the formal discussion has been given, and the numerical results have not yet been reported. The combination between enzyme and substrate is not only non-spherically symmetric, but also related to the force field existing between the reacting molecules. In the previous article we introduced the spatial factor and the force field factor and derived a general equation for these reaction systems. We present in this article a general method for finding the numerical solution of the above equation. With the numerical results obtained by this method we may interpret the experimental facts which can not be explained from the viewpoint of the classical diffusion-controlled reaction theory. In order to examine more closely the kinetic behaviour of enzyme-substrate reaction systems, we defined several characteristic parameters. The quantitative relation between these parameters and the rate of diffusion-controlled reaction has been discussed.", "contents": "The quantitative relations between diffusion-controlled reaction rate and characteristic parameters in enzyme-substrate reaction systems. I. Neutral substrates. With the development of techniques for studying fast reactions, we are confronted with some experimental observations which, according to the classical diffusion-controlled reaction theory based on the assumption of pherical symmetry, will lead to paradoxical consequences. Recently, some investigators have attempted to present a theory of non-spherically symmetric diffusion-controlled reaction. Owing to the difficulty in mathematics, only the formal discussion has been given, and the numerical results have not yet been reported. The combination between enzyme and substrate is not only non-spherically symmetric, but also related to the force field existing between the reacting molecules. In the previous article we introduced the spatial factor and the force field factor and derived a general equation for these reaction systems. We present in this article a general method for finding the numerical solution of the above equation. With the numerical results obtained by this method we may interpret the experimental facts which can not be explained from the viewpoint of the classical diffusion-controlled reaction theory. In order to examine more closely the kinetic behaviour of enzyme-substrate reaction systems, we defined several characteristic parameters. The quantitative relation between these parameters and the rate of diffusion-controlled reaction has been discussed."} {"id": "PMID:1273574", "title": "Western pine beetle: specificity among enantiomers of male and female components of an attractant pheromone.", "content": "The flight response of both sexes of Dendroctonus brevicomis to the mixture of myrcene, racemic frontalin, and (1R,5S,7R)-(+)-exo-brevicomin and to the mixture of myrcene, (1S,5R)-(-)-frontalin and racemic exo-brevicomin was significantly greater than the response to the same mixtures in which the antipodes were substituted. The flight response to these two mixtures was also greater than the response to the ternary mixture of myrcene, racemic frontalin, and racemic exo-brevicomin (MFE). The walking response of both sexes to the mixture of myrcene, racemic frontalin, and (+)-exo-brevicomin was not different from the response to MFE. Substitution of the antipode lowered the response when compared to that of MFE. When evaporated with ponderosa pine turpentine, (-)-frontalin was active in the field while its antipode was not.", "contents": "Western pine beetle: specificity among enantiomers of male and female components of an attractant pheromone. The flight response of both sexes of Dendroctonus brevicomis to the mixture of myrcene, racemic frontalin, and (1R,5S,7R)-(+)-exo-brevicomin and to the mixture of myrcene, (1S,5R)-(-)-frontalin and racemic exo-brevicomin was significantly greater than the response to the same mixtures in which the antipodes were substituted. The flight response to these two mixtures was also greater than the response to the ternary mixture of myrcene, racemic frontalin, and racemic exo-brevicomin (MFE). The walking response of both sexes to the mixture of myrcene, racemic frontalin, and (+)-exo-brevicomin was not different from the response to MFE. Substitution of the antipode lowered the response when compared to that of MFE. When evaporated with ponderosa pine turpentine, (-)-frontalin was active in the field while its antipode was not."} {"id": "PMID:1273572", "title": "Localization of central structures involved in descending inhibitory effect of acupuncture on viscero-somatic reflex discharges.", "content": "The pain reaction provoked by visceral traction has been one of the main problems to be solved in acupuncture anesthesia. By means of recording the viscero-somatic reflex activity in the animals, we have found that this reflex activity can be inhibited by acupuncture, and that the inhibitory effect originates from the supraspinal structures. The central structures involved in the inhibitory effect of acupuncture have been identified in a series of transection and lesion experiments. In decerebrated animals the inhibitory effect during acupuncture was preserved, but the after-inhibition of acupuncture disappeared; transection at the lower medulla as well as the cervical cord abolished near completely the whole inhibitory effect of acupuncture; a median lesion in the medulla including the nucleus raphe maguns resulted in a significant decrease of the inhibitory effect during acupuncture and a complete disappearance of the after-inhibition of acupuncture. The available evidence indicates that the median region of the medulla is involved in the elaboration of the inhibitory effect of acupuncture on the viscero-somatic reflex. A suggestion is thus offered that these supraspinal structures may be the essential link of the centre which is activated by acupuncture and involved in the descending inhibitory influence on the pain reaction of visceral stimulation.", "contents": "Localization of central structures involved in descending inhibitory effect of acupuncture on viscero-somatic reflex discharges. The pain reaction provoked by visceral traction has been one of the main problems to be solved in acupuncture anesthesia. By means of recording the viscero-somatic reflex activity in the animals, we have found that this reflex activity can be inhibited by acupuncture, and that the inhibitory effect originates from the supraspinal structures. The central structures involved in the inhibitory effect of acupuncture have been identified in a series of transection and lesion experiments. In decerebrated animals the inhibitory effect during acupuncture was preserved, but the after-inhibition of acupuncture disappeared; transection at the lower medulla as well as the cervical cord abolished near completely the whole inhibitory effect of acupuncture; a median lesion in the medulla including the nucleus raphe maguns resulted in a significant decrease of the inhibitory effect during acupuncture and a complete disappearance of the after-inhibition of acupuncture. The available evidence indicates that the median region of the medulla is involved in the elaboration of the inhibitory effect of acupuncture on the viscero-somatic reflex. A suggestion is thus offered that these supraspinal structures may be the essential link of the centre which is activated by acupuncture and involved in the descending inhibitory influence on the pain reaction of visceral stimulation."} {"id": "PMID:1273575", "title": "Nuclear magnetic resonance patterns of intracellular water as a function of HeLa cell cycle.", "content": "Nuclear magnetic resonance relaxation time (T1) of the intracellular water protons and water content were measured in synchronized HeLa cells. The T1 was maximum (1020 milliseconds) in mitotic and minimum (534 milliseconds) in S phase cells. The cyclic pattern of T1 values correlated well with the chromosome condensation cycle. By treating cells with spermine, it was possible to alter T1 without a significant change in the water content. The results of this study suggest that an additional variable, namely, the conformational state of macromolecules, should be incluced in any expression explaining the shortened relaxation times of water protons in biological systems.", "contents": "Nuclear magnetic resonance patterns of intracellular water as a function of HeLa cell cycle. Nuclear magnetic resonance relaxation time (T1) of the intracellular water protons and water content were measured in synchronized HeLa cells. The T1 was maximum (1020 milliseconds) in mitotic and minimum (534 milliseconds) in S phase cells. The cyclic pattern of T1 values correlated well with the chromosome condensation cycle. By treating cells with spermine, it was possible to alter T1 without a significant change in the water content. The results of this study suggest that an additional variable, namely, the conformational state of macromolecules, should be incluced in any expression explaining the shortened relaxation times of water protons in biological systems."} {"id": "PMID:1273576", "title": "Vasoactive intestinal polypeptide: abundant immunoreactivity in neural cell lines and normal nervous tissue.", "content": "Vasoactive intestinal polypeptide immunoreactivity is present in high concentrations in clonal lines of neuronal and glial origin. The central nervous system and sympathetic ganglia are also rich in the peptide. The findings suggest that this peptide, hitherto thought limited to the gastrointestinal tract, is widely distributed in neural tissue and may have broad physiological significance.", "contents": "Vasoactive intestinal polypeptide: abundant immunoreactivity in neural cell lines and normal nervous tissue. Vasoactive intestinal polypeptide immunoreactivity is present in high concentrations in clonal lines of neuronal and glial origin. The central nervous system and sympathetic ganglia are also rich in the peptide. The findings suggest that this peptide, hitherto thought limited to the gastrointestinal tract, is widely distributed in neural tissue and may have broad physiological significance."} {"id": "PMID:1273577", "title": "Human handedness: a partial cross-fostering study.", "content": "The hand preference of college students correlated significantly with the writing hand of their biological parents but not that of their stepparents. The results are consistent with a genetic theory of the origin of human handedness.", "contents": "Human handedness: a partial cross-fostering study. The hand preference of college students correlated significantly with the writing hand of their biological parents but not that of their stepparents. The results are consistent with a genetic theory of the origin of human handedness."} {"id": "PMID:1273579", "title": "Tunneling in ligand binding to heme proteins.", "content": "Rebinding of carbon monoxide to the beta chain of hemoglobin after photodissociation by a laser flash is intramolecular below about 200 K. Above 25 K, rebinding occurs via classical over-the-barrier motion; below, quantum-mechanical tunneling dominates. Both are described by an energy spectrum peaked at Epeak=4.0 kilojoules per mole. The barrier width d(E), determined from the energy dependence of the tunneling rate, depends on barrier height, d(E) approximately 0.05 nanometer X (E/Epeak) 1.5.", "contents": "Tunneling in ligand binding to heme proteins. Rebinding of carbon monoxide to the beta chain of hemoglobin after photodissociation by a laser flash is intramolecular below about 200 K. Above 25 K, rebinding occurs via classical over-the-barrier motion; below, quantum-mechanical tunneling dominates. Both are described by an energy spectrum peaked at Epeak=4.0 kilojoules per mole. The barrier width d(E), determined from the energy dependence of the tunneling rate, depends on barrier height, d(E) approximately 0.05 nanometer X (E/Epeak) 1.5."} {"id": "PMID:1273580", "title": "Wastewater renovation and reuse: virus removal by soil filtration.", "content": "Secondary sewage effluent and renovated water from four wells at the Flushing Meadows Wastewater Renovation Project near Phoenix, Arizona, in operation since 1967, were assayed approximately every 2 months in 1974 for viruses during flooding periods. Viruses, regularly found in the secondary effluent, were not detected in any renovated water samples. Our results indicated that human viral pathogens do not move through soil into the groundwater, but are apparently absorbed and degraded by the soil and reduced in numbers by a factor of at least 10(4) (99.99 percent removal).", "contents": "Wastewater renovation and reuse: virus removal by soil filtration. Secondary sewage effluent and renovated water from four wells at the Flushing Meadows Wastewater Renovation Project near Phoenix, Arizona, in operation since 1967, were assayed approximately every 2 months in 1974 for viruses during flooding periods. Viruses, regularly found in the secondary effluent, were not detected in any renovated water samples. Our results indicated that human viral pathogens do not move through soil into the groundwater, but are apparently absorbed and degraded by the soil and reduced in numbers by a factor of at least 10(4) (99.99 percent removal)."} {"id": "PMID:1273581", "title": "Neuroendocrine (bag) cells of Aplysia: spike blockade and a mechanism for potentiation.", "content": "Bag cell activity in Aplysia can be recorded intracellularly and extracellularly. Electrical stimulation anywhere along the connective nerves can produce prepotentials which are not synaptic potentials but represent the passive invasion of action potentials blocked in the neurites. Potentiation of these prepotentials results from progressive movement of the site of spike blockade toward the somata. This type of propagation plasticity may occur in many networks of low conduction safety.", "contents": "Neuroendocrine (bag) cells of Aplysia: spike blockade and a mechanism for potentiation. Bag cell activity in Aplysia can be recorded intracellularly and extracellularly. Electrical stimulation anywhere along the connective nerves can produce prepotentials which are not synaptic potentials but represent the passive invasion of action potentials blocked in the neurites. Potentiation of these prepotentials results from progressive movement of the site of spike blockade toward the somata. This type of propagation plasticity may occur in many networks of low conduction safety."} {"id": "PMID:1273582", "title": "Sodium arachidonate can induce platelet shape change and aggregation which are independent of the release reaction.", "content": "Sodium arachidonate causes shape change and aggregation of rabbit or human platelets that have been washed and then degranulated by treatment with thrombin. Since these platelets do not contain releasable adenosine diphosphate (ADP) and the aggregation is not inhibited by the creatine phosphate-creatine phosphokinase system, sodium arachidonate must be able to cause aggregation that is independent of the release of ADP. Since aggregation of these platelets induced by sodium arachidonate is inhibited by acetylsalicylic acid or indomethacin, it seems likely that products (such as prostaglandin G2) formed from sodium arachidonate are responsible for aggregation. Thus, sodium arachidonate-induced shape change and aggregation of platelets may be caused (i) by the release of ADP by products of sodium arachidonate metabolism and (ii) directly by the products of sodium arachidonate metabolism, independently of released ADP.", "contents": "Sodium arachidonate can induce platelet shape change and aggregation which are independent of the release reaction. Sodium arachidonate causes shape change and aggregation of rabbit or human platelets that have been washed and then degranulated by treatment with thrombin. Since these platelets do not contain releasable adenosine diphosphate (ADP) and the aggregation is not inhibited by the creatine phosphate-creatine phosphokinase system, sodium arachidonate must be able to cause aggregation that is independent of the release of ADP. Since aggregation of these platelets induced by sodium arachidonate is inhibited by acetylsalicylic acid or indomethacin, it seems likely that products (such as prostaglandin G2) formed from sodium arachidonate are responsible for aggregation. Thus, sodium arachidonate-induced shape change and aggregation of platelets may be caused (i) by the release of ADP by products of sodium arachidonate metabolism and (ii) directly by the products of sodium arachidonate metabolism, independently of released ADP."} {"id": "PMID:1273583", "title": "Human bloodstains: individualization by crossed electroimmunodiffusion.", "content": "Crossed electroimmunodiffusion was evaluated as a means for establishing the individuality (\"fingerprinting\") of human bloodstains. In ten separate examinations on stains from each of ten persons there was at least one peak with a unique range in height so that individualization was possible. The heights of certain peaks showed statistically significant female-male differences.", "contents": "Human bloodstains: individualization by crossed electroimmunodiffusion. Crossed electroimmunodiffusion was evaluated as a means for establishing the individuality (\"fingerprinting\") of human bloodstains. In ten separate examinations on stains from each of ten persons there was at least one peak with a unique range in height so that individualization was possible. The heights of certain peaks showed statistically significant female-male differences."} {"id": "PMID:1273584", "title": "Monoamine oxidase activity decreased in cells lacking hypoxanthine phosphoribosyltransferase activity.", "content": "The Lesch-Nyhan syndrome in humans is characterized by lack of hypoxanthine phosphoribosyltransferase activity and neurologic abnormalities that suggest changes in catecholamine metabolism. Monoamine oxidase, which degrades biogenic amines, has decreased activity in noradrenergic murine neuroblastoma cell lines lacking hypoxanthine phosphoribosyltransferase activity and in skin fibroblasts from patients with the Lesch-Nyhan syndrome.", "contents": "Monoamine oxidase activity decreased in cells lacking hypoxanthine phosphoribosyltransferase activity. The Lesch-Nyhan syndrome in humans is characterized by lack of hypoxanthine phosphoribosyltransferase activity and neurologic abnormalities that suggest changes in catecholamine metabolism. Monoamine oxidase, which degrades biogenic amines, has decreased activity in noradrenergic murine neuroblastoma cell lines lacking hypoxanthine phosphoribosyltransferase activity and in skin fibroblasts from patients with the Lesch-Nyhan syndrome."} {"id": "PMID:1273585", "title": "Ultrastructure of the auditory regions in the inner ear of the lake whitefish.", "content": "Hair cell polarization patterns were investigated on the sensory macule of the sacculus and lagena of the lake whitefish. The saccular hair cells are divided into four groups, with all of the cells within a group having the same orientation. Saccular orientations are anterior, posterior, dorsal, and ventral with respect to the axis of the animal. Two groups, one dorsal and one ventral, are found on the lagena. The saccular orientations are significantly different from those in tetrapods. Since this organ appears to have different functions in fish and tetrapods it is likely that the orientation patterns in fish are adapted to some aspect of audition--perhaps directional localization of sound.", "contents": "Ultrastructure of the auditory regions in the inner ear of the lake whitefish. Hair cell polarization patterns were investigated on the sensory macule of the sacculus and lagena of the lake whitefish. The saccular hair cells are divided into four groups, with all of the cells within a group having the same orientation. Saccular orientations are anterior, posterior, dorsal, and ventral with respect to the axis of the animal. Two groups, one dorsal and one ventral, are found on the lagena. The saccular orientations are significantly different from those in tetrapods. Since this organ appears to have different functions in fish and tetrapods it is likely that the orientation patterns in fish are adapted to some aspect of audition--perhaps directional localization of sound."} {"id": "PMID:1273586", "title": "Vibrational spectroscopy of chemisorbed fatty acids with inelastic electron tunneling.", "content": "We have measured and assigned the inelastic tunneling spectra of hexanoic acid chemisorbed onto an oxidized aluminum file. We present evidence for gauche-trans as well as-trans conformers in the monolayer and evidence in support of a recent theory of tunneling intensities.", "contents": "Vibrational spectroscopy of chemisorbed fatty acids with inelastic electron tunneling. We have measured and assigned the inelastic tunneling spectra of hexanoic acid chemisorbed onto an oxidized aluminum file. We present evidence for gauche-trans as well as-trans conformers in the monolayer and evidence in support of a recent theory of tunneling intensities."} {"id": "PMID:1273587", "title": "Thrombosis in association with atherosclerosis induced by dietary perturbations in dogs.", "content": "The distribution, severity, and complications of diet-induced atherosclerosis in dogs can be altered by changing the source of fat in the diet. Thrombosis and thromboembolic disease associated with atherosclerosis occurred with diets containing beef tallow and lard of coconut oil but were absent in dogs fed cottonseed oil as a source of fat. Experiemtnal animals with and without thrombosis are of value as models in elucidating the role of platelets and thrombostatic mechanisms in atherosclerosis.", "contents": "Thrombosis in association with atherosclerosis induced by dietary perturbations in dogs. The distribution, severity, and complications of diet-induced atherosclerosis in dogs can be altered by changing the source of fat in the diet. Thrombosis and thromboembolic disease associated with atherosclerosis occurred with diets containing beef tallow and lard of coconut oil but were absent in dogs fed cottonseed oil as a source of fat. Experiemtnal animals with and without thrombosis are of value as models in elucidating the role of platelets and thrombostatic mechanisms in atherosclerosis."} {"id": "PMID:1273589", "title": "Ingestion of Streptococcus mutans induces secretory immunoglobulin A and caries immunity.", "content": "Ingestion of killed cells of a highly cariogenic strain of Streptococcus mutans induced specific antibodies in both saliva and milk but not in serum of gnotobiotic rats. These antibodies were associated with the immunoglobulin A class. When infected with Streptococcus mutans, orally immunized animals developed significantly fewer carious lesions than nonimmunized infected controls.", "contents": "Ingestion of Streptococcus mutans induces secretory immunoglobulin A and caries immunity. Ingestion of killed cells of a highly cariogenic strain of Streptococcus mutans induced specific antibodies in both saliva and milk but not in serum of gnotobiotic rats. These antibodies were associated with the immunoglobulin A class. When infected with Streptococcus mutans, orally immunized animals developed significantly fewer carious lesions than nonimmunized infected controls."} {"id": "PMID:1273590", "title": "Imprinting to chemical cues: the basis for home stream selection in salmon.", "content": "Juvenile coho salmon were exposed to morpholine or phenethyl alcohol (p-alcohol) for 1 1/2 months and then released in Lake Michigan. During the spawning migration 18 months later, morpholine and p-alcohol were metered into separate streams, and the number of morpholine- and p-alcohol-exposed fish returning to each stream was determined. Seventeen other locations were also monitored. The majority of the fish exposed to morpholine were captured in the stream scented with morpholine and most fish exposed to p-alcohol were captured at the p-alcohol-treated stream. This field study demonstrates that coho salmon imprint to and utilize chemical cues for homing.", "contents": "Imprinting to chemical cues: the basis for home stream selection in salmon. Juvenile coho salmon were exposed to morpholine or phenethyl alcohol (p-alcohol) for 1 1/2 months and then released in Lake Michigan. During the spawning migration 18 months later, morpholine and p-alcohol were metered into separate streams, and the number of morpholine- and p-alcohol-exposed fish returning to each stream was determined. Seventeen other locations were also monitored. The majority of the fish exposed to morpholine were captured in the stream scented with morpholine and most fish exposed to p-alcohol were captured at the p-alcohol-treated stream. This field study demonstrates that coho salmon imprint to and utilize chemical cues for homing."} {"id": "PMID:1273591", "title": "Residual learning deficit after heavy exposure to cannabis or alcohol in rats.", "content": "Acute oral administration of cannabis extract to rats (tetrahydrocannabinol dose, 10 milligrams per kilogram) impaired maze learning. The impairment was more marked after ten daily doses of the same size. After 1, 2, or 3 months' pretreatment with the same daily dose, followed by a 25-day drug-free period, no residual learning impairment was found. However, 6 months of daily administration of cannabis (tetrahydrocannabinol, 20 milligrams per kilogram) or alcohol (6 grams per kilogram) produced significant residual impairment of learning of maze and motor coordination tasks, 2 months or more after the last drug administration.", "contents": "Residual learning deficit after heavy exposure to cannabis or alcohol in rats. Acute oral administration of cannabis extract to rats (tetrahydrocannabinol dose, 10 milligrams per kilogram) impaired maze learning. The impairment was more marked after ten daily doses of the same size. After 1, 2, or 3 months' pretreatment with the same daily dose, followed by a 25-day drug-free period, no residual learning impairment was found. However, 6 months of daily administration of cannabis (tetrahydrocannabinol, 20 milligrams per kilogram) or alcohol (6 grams per kilogram) produced significant residual impairment of learning of maze and motor coordination tasks, 2 months or more after the last drug administration."} {"id": "PMID:1273592", "title": "N-nitroso compounds: detection in ambient air.", "content": "By use of a new, highly selective detection technique for N-nitroso compounds, which is sensitive to picogram quantities and which is based on the catalytic cleavage of the N-NO bond and the subsequent detection of the nitrosyl radical, dimethylnitrosamine has been found in concentrations of 0.02 to 0.96 part per billion in three out of five air samples from Baltimore, Maryland, and 0.014 to 0.051 part per billion in five out of six air samples from Belle, West Virginia. The sensitivity of the analytical procedures used was 1 part in 10(12). The presence of dimethylnitrosamine has been confirmed by using the new detector in conjunction with both a gas-liquid chromatograph and a high-performance liquid chromatograph. In addition, between one and three as yet unidentified N-nitroso compounds were detected in both cities. N-Nitroso compounds were not found in air samples from Philadelphia, Pennsylvania; Wilmington, Delaware; and Waltham, Massachusetts.", "contents": "N-nitroso compounds: detection in ambient air. By use of a new, highly selective detection technique for N-nitroso compounds, which is sensitive to picogram quantities and which is based on the catalytic cleavage of the N-NO bond and the subsequent detection of the nitrosyl radical, dimethylnitrosamine has been found in concentrations of 0.02 to 0.96 part per billion in three out of five air samples from Baltimore, Maryland, and 0.014 to 0.051 part per billion in five out of six air samples from Belle, West Virginia. The sensitivity of the analytical procedures used was 1 part in 10(12). The presence of dimethylnitrosamine has been confirmed by using the new detector in conjunction with both a gas-liquid chromatograph and a high-performance liquid chromatograph. In addition, between one and three as yet unidentified N-nitroso compounds were detected in both cities. N-Nitroso compounds were not found in air samples from Philadelphia, Pennsylvania; Wilmington, Delaware; and Waltham, Massachusetts."} {"id": "PMID:1273593", "title": "Bone cells in culture: morphologic transformation by hormones.", "content": "Hormones and purine nucleosides and nucleotides induced cultured bone cells to transform transiently from a spherical to a stellate shape. Cytochalasin B also induced the transformation. The change was blocked by colchicine and vinblastine, but not by lumicolchicine or cycloheximide. This morphologic transformation may provide a dynamic model of hormone action and bone cell modulation in vitro.", "contents": "Bone cells in culture: morphologic transformation by hormones. Hormones and purine nucleosides and nucleotides induced cultured bone cells to transform transiently from a spherical to a stellate shape. Cytochalasin B also induced the transformation. The change was blocked by colchicine and vinblastine, but not by lumicolchicine or cycloheximide. This morphologic transformation may provide a dynamic model of hormone action and bone cell modulation in vitro."} {"id": "PMID:1273594", "title": "Aflatoxin production by a variant of Aspergillus oryzae (NRRL strain 1988) on cowpeas (Vigna sinensis).", "content": "Aflatoxin B1, B2, G1, and G2 are produced when a variant of Aspergillus oryzae (NRRL strain 1988) is grown on cowpeas or rice. The present study indicates that a strain of Aspergillus oryzae approved for use in food processing is variable and the resulting variant, unlike the parent strain, has a propensity to produce aflatoxin.", "contents": "Aflatoxin production by a variant of Aspergillus oryzae (NRRL strain 1988) on cowpeas (Vigna sinensis). Aflatoxin B1, B2, G1, and G2 are produced when a variant of Aspergillus oryzae (NRRL strain 1988) is grown on cowpeas or rice. The present study indicates that a strain of Aspergillus oryzae approved for use in food processing is variable and the resulting variant, unlike the parent strain, has a propensity to produce aflatoxin."} {"id": "PMID:1273595", "title": "Ant-aphid association: role of aphid alarm pheromone.", "content": "When attacked by predators, aphids secrete alarm pheromones that cause nearby aphids to disperse. Ant-associated (myrmecophilous) aphid species disperse less readily than nonmyrmecophilous species. The ant Formica subsericea responds to aphid alarm pheromone in a way that is beneficial to the aphid. These findings support our hypothesis that myrmecophilous aphids depend more on ants for protection from predators than on their own dispersive powers.", "contents": "Ant-aphid association: role of aphid alarm pheromone. When attacked by predators, aphids secrete alarm pheromones that cause nearby aphids to disperse. Ant-associated (myrmecophilous) aphid species disperse less readily than nonmyrmecophilous species. The ant Formica subsericea responds to aphid alarm pheromone in a way that is beneficial to the aphid. These findings support our hypothesis that myrmecophilous aphids depend more on ants for protection from predators than on their own dispersive powers."} {"id": "PMID:1273596", "title": "Stimulant-related state-dependent learning in hyperactive children.", "content": "Hyperactive and nonhyperactive children performed a learning task in two states, while being treated with stimulant medication (methylphenidate) and while taking a placebo, and were tested for retention of each class of learned material in both states. Symmetrical state-dependent learning was demonstrated in the hyperactive group but not in the nonhyperactive group. The state-dependent effect was contingent on the presence of drug-induced facilitation during initial learning. This is apparently the first report on record of state-dependent learning with a drug agent that facilitates rather than impairs performance of human subjects.", "contents": "Stimulant-related state-dependent learning in hyperactive children. Hyperactive and nonhyperactive children performed a learning task in two states, while being treated with stimulant medication (methylphenidate) and while taking a placebo, and were tested for retention of each class of learned material in both states. Symmetrical state-dependent learning was demonstrated in the hyperactive group but not in the nonhyperactive group. The state-dependent effect was contingent on the presence of drug-induced facilitation during initial learning. This is apparently the first report on record of state-dependent learning with a drug agent that facilitates rather than impairs performance of human subjects."} {"id": "PMID:1273597", "title": "Analgesia mediated by a direct spinal action of narcotics.", "content": "Narcotic analgetics administered directly into the spinal subarachnoid space of the rat via a chronically inserted catheter produce a potent analgesia that can be antagonized by naloxone. The narcotics, acting only at the spinal level, changed cord function to block not only spinal reflexes but also the operant response to painful stimuli.", "contents": "Analgesia mediated by a direct spinal action of narcotics. Narcotic analgetics administered directly into the spinal subarachnoid space of the rat via a chronically inserted catheter produce a potent analgesia that can be antagonized by naloxone. The narcotics, acting only at the spinal level, changed cord function to block not only spinal reflexes but also the operant response to painful stimuli."} {"id": "PMID:1273598", "title": "Evolution on the level of communities.", "content": "According to traditional models, natural selection is largely insensitive to an organism's effect on its community. Effects on the community at large cannot feed back differentially to the organisms that cause them, and, hence, cannot lead to the differential fitness of the organisms. However, if a spatial variation exists in community composition, organisms do differentially feel their own effects on the community, and this leads to a form of evolution on the community level. Without violating the principle of individual selection, the concept of an organism that exists for the \"function\" its performs in its community may be valid in some cases.", "contents": "Evolution on the level of communities. According to traditional models, natural selection is largely insensitive to an organism's effect on its community. Effects on the community at large cannot feed back differentially to the organisms that cause them, and, hence, cannot lead to the differential fitness of the organisms. However, if a spatial variation exists in community composition, organisms do differentially feel their own effects on the community, and this leads to a form of evolution on the community level. Without violating the principle of individual selection, the concept of an organism that exists for the \"function\" its performs in its community may be valid in some cases."} {"id": "PMID:1273600", "title": "Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome.", "content": "The early course of newly diagnosed RA among young adult patients (16-44 yr) is described from results of an ongoing study with a mean follow-up of 3.4 yr. Study diagnosis was based on the judgement of experienced rheumatologists, and data on several hundred variables were obtained on entry and annually for the purpose of defining patterns of onset and course of disease. Race and sex factors, as well as certain entry manifestations, e.g., RF, were found to correlate with onset and course patterns. Females, and especially white females, had significantly greater numbers of swollen upper extremity joints than males at entry and at last observation, with increased likelihood of developing bone erosions. At entry, RF positive patients differed only on few articular manifestations from RF negative patients, but had a higher frequency of positive ANA at entry and more subcutaneous nodules and bone erosions during follow-up. Seropositive white females at entry had significantly more swollen upper joints than their seronegative counterparts, but with no difference found at last follow-up. White females of each serogroup had more joint involvement at last examination than patients of other race-sex groups. Males had more acute onset, especially under age 30, with significantly greater improvement in arthritis and in ESR than did females. The majority (55%) of patients entered as seropositive, converted to seronegative during follow-up, and no correlation of either joint swelling or erosions was noted with this phenomenon. At last visit, RF positively did not correlate with bone erosions, but patients developing bone erosions had higher frequency of ANA and higher mean serum complement levels at last examination. The following entry factors were found to correlate significantly with a better outcome: maleness, acute onset under age 30, less swollen upper joints, and negative RF. Type of drug therapy tended to reflect severity of arthritis, rather than vice versa, and functional capacity improved significantly from entry to last evaluation in both males and females, even though the latter had stable or progressive arthritis. Further study is necessary over long intervals and in wider age range to more adequately interpret the biologic implications of findings of this ongoing study. A better understanding of the pathogenesis of RA may be derived from critical studies of the contribution of host factors, e.g., sex, and other variables predisposing to the development of RF positivity (and ANA), subcutaneous nodules, and bone erosions, particularly in systematic ongoing studies of patients with early diagnosed disease.", "contents": "Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome. The early course of newly diagnosed RA among young adult patients (16-44 yr) is described from results of an ongoing study with a mean follow-up of 3.4 yr. Study diagnosis was based on the judgement of experienced rheumatologists, and data on several hundred variables were obtained on entry and annually for the purpose of defining patterns of onset and course of disease. Race and sex factors, as well as certain entry manifestations, e.g., RF, were found to correlate with onset and course patterns. Females, and especially white females, had significantly greater numbers of swollen upper extremity joints than males at entry and at last observation, with increased likelihood of developing bone erosions. At entry, RF positive patients differed only on few articular manifestations from RF negative patients, but had a higher frequency of positive ANA at entry and more subcutaneous nodules and bone erosions during follow-up. Seropositive white females at entry had significantly more swollen upper joints than their seronegative counterparts, but with no difference found at last follow-up. White females of each serogroup had more joint involvement at last examination than patients of other race-sex groups. Males had more acute onset, especially under age 30, with significantly greater improvement in arthritis and in ESR than did females. The majority (55%) of patients entered as seropositive, converted to seronegative during follow-up, and no correlation of either joint swelling or erosions was noted with this phenomenon. At last visit, RF positively did not correlate with bone erosions, but patients developing bone erosions had higher frequency of ANA and higher mean serum complement levels at last examination. The following entry factors were found to correlate significantly with a better outcome: maleness, acute onset under age 30, less swollen upper joints, and negative RF. Type of drug therapy tended to reflect severity of arthritis, rather than vice versa, and functional capacity improved significantly from entry to last evaluation in both males and females, even though the latter had stable or progressive arthritis. Further study is necessary over long intervals and in wider age range to more adequately interpret the biologic implications of findings of this ongoing study. A better understanding of the pathogenesis of RA may be derived from critical studies of the contribution of host factors, e.g., sex, and other variables predisposing to the development of RF positivity (and ANA), subcutaneous nodules, and bone erosions, particularly in systematic ongoing studies of patients with early diagnosed disease."} {"id": "PMID:1273603", "title": "Assessment of intrarenal perfusion with radioxenon: a critical review of analytical factors and their implications in man.", "content": "Radioxenon has achieved wide use for assessing tissue perfusion. Here we review its application to the kidney for assessing mean blood flow and intrarenal perfusion rates. Correlation with alternative methods in animals suggests that the initial disappearance slope provides an adequate measure of mean renal blood flow despite the theoretical limitations of this approach. The stochastic method and compartmental analysis can also provide an acceptable measure fo mean renal blood flow, but only after the slowest flow components have been removed. Compartmental analysis does, however, provide an index of cortical perfusion not available from other methods. The evidence that the rapid component of xenon washout provides an index of cortical perfusion in man is reviewed, along with insights gained from the application of this approach to human disease.", "contents": "Assessment of intrarenal perfusion with radioxenon: a critical review of analytical factors and their implications in man. Radioxenon has achieved wide use for assessing tissue perfusion. Here we review its application to the kidney for assessing mean blood flow and intrarenal perfusion rates. Correlation with alternative methods in animals suggests that the initial disappearance slope provides an adequate measure of mean renal blood flow despite the theoretical limitations of this approach. The stochastic method and compartmental analysis can also provide an acceptable measure fo mean renal blood flow, but only after the slowest flow components have been removed. Compartmental analysis does, however, provide an index of cortical perfusion not available from other methods. The evidence that the rapid component of xenon washout provides an index of cortical perfusion in man is reviewed, along with insights gained from the application of this approach to human disease."} {"id": "PMID:1273607", "title": "Fiberoptic colonoscopy: diagnostic value in 250 consecutive patients.", "content": "Endoscopic findings and accomplishments in 250 consecutive patients are presented. Of these patients 72% were found to have polyps, cancer, inflammatory bowel disease or other specific positive findings. In almost half of these patients, no definitive diagnosis had been made before the procedure. In half of the patients, new information was obtained which was not known before the procedure. Indications for colonoscopy are presented to demonstrate the situations in which the procedure was valuable not only to remove polyps, but also to explain nonspecific radiologic abnormalities, unexplained rectal bleeding, or diarrhea, and to detect unknown cancers and polyps.", "contents": "Fiberoptic colonoscopy: diagnostic value in 250 consecutive patients. Endoscopic findings and accomplishments in 250 consecutive patients are presented. Of these patients 72% were found to have polyps, cancer, inflammatory bowel disease or other specific positive findings. In almost half of these patients, no definitive diagnosis had been made before the procedure. In half of the patients, new information was obtained which was not known before the procedure. Indications for colonoscopy are presented to demonstrate the situations in which the procedure was valuable not only to remove polyps, but also to explain nonspecific radiologic abnormalities, unexplained rectal bleeding, or diarrhea, and to detect unknown cancers and polyps."} {"id": "PMID:1273608", "title": "Unsuspected diabetic glomerulosclerosis.", "content": "Six patients without overt diabetes mellitus underwent renal biopsy for suspected glomerulonephritis. All were demonstrated to have diabetic glomerulosclerosis and subsequently were found to have abnormal glucose tolerance tests. Electron microscopy was critical in making the correct diagnosis in five of six patients. The reported cases represent 3% of a series of 200 patients who had a renal biopsy to evaluate possible glomerulonephritis. Renal manifestations of diabetes mellitus may antedate glycosuria and other more common presenting symptoms of this disease.", "contents": "Unsuspected diabetic glomerulosclerosis. Six patients without overt diabetes mellitus underwent renal biopsy for suspected glomerulonephritis. All were demonstrated to have diabetic glomerulosclerosis and subsequently were found to have abnormal glucose tolerance tests. Electron microscopy was critical in making the correct diagnosis in five of six patients. The reported cases represent 3% of a series of 200 patients who had a renal biopsy to evaluate possible glomerulonephritis. Renal manifestations of diabetes mellitus may antedate glycosuria and other more common presenting symptoms of this disease."} {"id": "PMID:1273609", "title": "Penetrating injuries of the face and neck.", "content": "Experience with 547 consecutive cases of cervical and facial penetrating trauma has indicated the value of an individualized approach rather than a firm policy of exploration for all wounds penetrating the platysma. In addition, the accumulated data suggest that the concept of separate classes of carotid injuries based on presence or absence of neurologic deficits bears further evaluation with respect to the advisability of reconstituting carotid artery flow.", "contents": "Penetrating injuries of the face and neck. Experience with 547 consecutive cases of cervical and facial penetrating trauma has indicated the value of an individualized approach rather than a firm policy of exploration for all wounds penetrating the platysma. In addition, the accumulated data suggest that the concept of separate classes of carotid injuries based on presence or absence of neurologic deficits bears further evaluation with respect to the advisability of reconstituting carotid artery flow."} {"id": "PMID:1273610", "title": "A dynamic transpatellar approach to the knee.", "content": "This paper describes a transverse approach to the knee which gives unequalled access to the joint for extensive synovectomies, extensive surgical debridement, installation of total knee prostheses, or reduction of supracondylar fracture of the femur involving the articular surfaces. The temporary patellar tendon substitution wire is a loop of wire extending through the body of the patella and intrapatellar tendon to the tibial tubercle, which restores the anatomic length of the patella and intrapatellar tendon, having sufficient strength to permit early motion of the joint, since the temporary patellar tendon substitution wire relieves stress from the capsular sutures.", "contents": "A dynamic transpatellar approach to the knee. This paper describes a transverse approach to the knee which gives unequalled access to the joint for extensive synovectomies, extensive surgical debridement, installation of total knee prostheses, or reduction of supracondylar fracture of the femur involving the articular surfaces. The temporary patellar tendon substitution wire is a loop of wire extending through the body of the patella and intrapatellar tendon to the tibial tubercle, which restores the anatomic length of the patella and intrapatellar tendon, having sufficient strength to permit early motion of the joint, since the temporary patellar tendon substitution wire relieves stress from the capsular sutures."} {"id": "PMID:1273611", "title": "Intradermal 5-fluorouracil in the treatment of basal cell carcinoma of the face.", "content": "The intradermal or infiltrative use of 5-fluorouracil by hypodermic syringe has resulted in the salvage of treatment failures of multifocal basal cell carcinoma of the face. This method is simple and safe, and the initial results have been excellent. It is an effective modality, especially in infiltrating lesions, and it produces little desquamation or side effects and no damage to the surrounding normal skin. Four cases are presented to illustrate how this method has eliminated the need for ablative surgery.", "contents": "Intradermal 5-fluorouracil in the treatment of basal cell carcinoma of the face. The intradermal or infiltrative use of 5-fluorouracil by hypodermic syringe has resulted in the salvage of treatment failures of multifocal basal cell carcinoma of the face. This method is simple and safe, and the initial results have been excellent. It is an effective modality, especially in infiltrating lesions, and it produces little desquamation or side effects and no damage to the surrounding normal skin. Four cases are presented to illustrate how this method has eliminated the need for ablative surgery."} {"id": "PMID:1273612", "title": "Long-term levodopa therapy for torsion dystonia.", "content": "Observation of a 34-year-old woman receiving levodopa for familial torsion dystonia over a four-year period revealed that severe side effects (gastrointestinal problems, dyskinesias, cramps, anxiety) occurred with maximal dosage schedules during the first ten months of treatment. Thereafter, a gradual reduction of the daily dose to 1,500 mg of levodopa gave excellent relief of hypokinesia and rigidity with minimal adverse effects, including abolition of mild akinesia paradoxica which developed after 2 1/2 years of treatment.", "contents": "Long-term levodopa therapy for torsion dystonia. Observation of a 34-year-old woman receiving levodopa for familial torsion dystonia over a four-year period revealed that severe side effects (gastrointestinal problems, dyskinesias, cramps, anxiety) occurred with maximal dosage schedules during the first ten months of treatment. Thereafter, a gradual reduction of the daily dose to 1,500 mg of levodopa gave excellent relief of hypokinesia and rigidity with minimal adverse effects, including abolition of mild akinesia paradoxica which developed after 2 1/2 years of treatment."} {"id": "PMID:1273613", "title": "Herpes zoster: correlation of age, sex, distribution, neuralgia, and associated disorders.", "content": "The influence of sex and age on the distribution of lesions, incidence of postherpetic neuralgia, and related disorders in herpes zoster is reported. Results were obtained by reviewing the records of 140 outpatients with herpes zoster seen over a ten-year period. Trigeminal involvement and post-herpetic neuralgia were more common in patients over 50 years of age. The most common sites of lesions in all ages were the thoracic dermatomes, between T-1 and T-8. The distribution of lesions and the incidence of postherpetic neuralgia did not vary between the sexes. High incidences of diabetes and cataracts were found to be associated with herpes zoster infection. Clinical carcinoma of the prostate was a frequent finding in men with herpes zoster over age 50. In those patients with malignancies, there was no correlation between distribution of zoster lesions and location of malignancy.", "contents": "Herpes zoster: correlation of age, sex, distribution, neuralgia, and associated disorders. The influence of sex and age on the distribution of lesions, incidence of postherpetic neuralgia, and related disorders in herpes zoster is reported. Results were obtained by reviewing the records of 140 outpatients with herpes zoster seen over a ten-year period. Trigeminal involvement and post-herpetic neuralgia were more common in patients over 50 years of age. The most common sites of lesions in all ages were the thoracic dermatomes, between T-1 and T-8. The distribution of lesions and the incidence of postherpetic neuralgia did not vary between the sexes. High incidences of diabetes and cataracts were found to be associated with herpes zoster infection. Clinical carcinoma of the prostate was a frequent finding in men with herpes zoster over age 50. In those patients with malignancies, there was no correlation between distribution of zoster lesions and location of malignancy."} {"id": "PMID:1273614", "title": "Hypophysectomy in the treatment of disseminated carcinoma of the breast and prostate gland.", "content": "Transsphenoidal hypophysectomy offers gratifying palliative relief of pain to patients with metastatic cancer of the breast and prostate. This report represents the results of two years' experience with this procedure at Emory University School of Medicine. The physiologic rationale and clinical indications for hypophysectomy are described, as is the operative technic using the open transsphenoidal microsurgical approach. The series of cases reported here includes 20 men with disseminated prostatic carcinoma and 23 women and one man with metastatic carcinoma of the breast. All 44 procedures were done by the transsphenoidal microsurgical approach. Pain was the preoperative indication for surgery in 41, while three patients were operated on for extensive disease without pain. Satisfactory relief of pain was obtained in 76% of the patients with prostatic cancer and in 83% of the breast cancer patients. While the results are gratifying with regard to relief of pain, the duration of follow-up is not sufficient to comment on the value of the procedure in significantly prolonging life.", "contents": "Hypophysectomy in the treatment of disseminated carcinoma of the breast and prostate gland. Transsphenoidal hypophysectomy offers gratifying palliative relief of pain to patients with metastatic cancer of the breast and prostate. This report represents the results of two years' experience with this procedure at Emory University School of Medicine. The physiologic rationale and clinical indications for hypophysectomy are described, as is the operative technic using the open transsphenoidal microsurgical approach. The series of cases reported here includes 20 men with disseminated prostatic carcinoma and 23 women and one man with metastatic carcinoma of the breast. All 44 procedures were done by the transsphenoidal microsurgical approach. Pain was the preoperative indication for surgery in 41, while three patients were operated on for extensive disease without pain. Satisfactory relief of pain was obtained in 76% of the patients with prostatic cancer and in 83% of the breast cancer patients. While the results are gratifying with regard to relief of pain, the duration of follow-up is not sufficient to comment on the value of the procedure in significantly prolonging life."} {"id": "PMID:1273615", "title": "Complications of peritoneal dialysis.", "content": "Peritoneal dialysis is an easily available therapeutic procedure. The complications noted in 490 dialyses over a six-year period in a university hospital have been reviewed. Seventeen major and 624 minor complications occurred. Only four deaths could be attributed to the procedure itself. Peritoneal dialysis is an effective procedure but one with a significant incidence of complications, though few of these are associated with mortality or morbidity for the patient. Various safeguards against these are discussed.", "contents": "Complications of peritoneal dialysis. Peritoneal dialysis is an easily available therapeutic procedure. The complications noted in 490 dialyses over a six-year period in a university hospital have been reviewed. Seventeen major and 624 minor complications occurred. Only four deaths could be attributed to the procedure itself. Peritoneal dialysis is an effective procedure but one with a significant incidence of complications, though few of these are associated with mortality or morbidity for the patient. Various safeguards against these are discussed."} {"id": "PMID:1273616", "title": "A new synthetic absorbable suture for ophthalmic surgery: laboratory and clinical evaluation.", "content": "A new synthetic absorbable suture for ophthalmic surgery--glycolactide--was proved superior to chromic collagen in rupture strength and more predictable absorption time in laboratory and clinical studies. The 8-0 glycolactide showed 30% greater initial strength than 8-0 chromic collagen. One week after implantation in rabbit corneas, the glycolactide retained over 90% of its initial rupture strength, while chromic collagen had lost nearly 50% of its strength. After ten days the strength of the glycolactide fell rapidly. By day 21 it began to be absorbed, completely disappearing by seven weeks. Chromic collagen tended to remain in situ longer, although possessing negligible rupture strength. The two materials were compared in suturing comeoscleral wounds of 45 consecutive patients undergoing routine cataract operation. The glycolactide began to disappear only after the fourth week, completely disappearing after nine weeks. Chromic collagen was more variable, some sutures disappearing as early as the third week, while others remained in place for over 20 weeks. Neither suture material excited reaction in the eyes, and the incidence of complications was low.", "contents": "A new synthetic absorbable suture for ophthalmic surgery: laboratory and clinical evaluation. A new synthetic absorbable suture for ophthalmic surgery--glycolactide--was proved superior to chromic collagen in rupture strength and more predictable absorption time in laboratory and clinical studies. The 8-0 glycolactide showed 30% greater initial strength than 8-0 chromic collagen. One week after implantation in rabbit corneas, the glycolactide retained over 90% of its initial rupture strength, while chromic collagen had lost nearly 50% of its strength. After ten days the strength of the glycolactide fell rapidly. By day 21 it began to be absorbed, completely disappearing by seven weeks. Chromic collagen tended to remain in situ longer, although possessing negligible rupture strength. The two materials were compared in suturing comeoscleral wounds of 45 consecutive patients undergoing routine cataract operation. The glycolactide began to disappear only after the fourth week, completely disappearing after nine weeks. Chromic collagen was more variable, some sutures disappearing as early as the third week, while others remained in place for over 20 weeks. Neither suture material excited reaction in the eyes, and the incidence of complications was low."} {"id": "PMID:1273617", "title": "The syndrome of retroperitoneal hemorrhage and lumbar plexus neuropathy during anticoagulant therapy.", "content": "A syndrome of retroperitoneal hemorrhage during anticoagulant therapy associated with nerve involvement in femoral nerve or lumbar plexus is described. Twenty-one cases were collected from the English-language literature, and five new cases were added for review and analysis. In these 26 cases spontaneous hemorrhage occurred under iliopsoas fascia in the retroperitoneal space. The clinical picture, involved nerves, laboratory findings of coagulation studies, anemia, and the outcome of these cases are summarized and discussed. Retroperitoneal space may contain a large quantity of internal hemorrhage. Irreversible damage of lumbar plexus or femoral nerve may result from entrapment of nerves in the hematoma. Laboratory coagulation studies may guide effective administration of anticoagulant therapy and minimize hemorrhagic complication, but they will not eliminate the risk of hemorrhage completely.", "contents": "The syndrome of retroperitoneal hemorrhage and lumbar plexus neuropathy during anticoagulant therapy. A syndrome of retroperitoneal hemorrhage during anticoagulant therapy associated with nerve involvement in femoral nerve or lumbar plexus is described. Twenty-one cases were collected from the English-language literature, and five new cases were added for review and analysis. In these 26 cases spontaneous hemorrhage occurred under iliopsoas fascia in the retroperitoneal space. The clinical picture, involved nerves, laboratory findings of coagulation studies, anemia, and the outcome of these cases are summarized and discussed. Retroperitoneal space may contain a large quantity of internal hemorrhage. Irreversible damage of lumbar plexus or femoral nerve may result from entrapment of nerves in the hematoma. Laboratory coagulation studies may guide effective administration of anticoagulant therapy and minimize hemorrhagic complication, but they will not eliminate the risk of hemorrhage completely."} {"id": "PMID:1273618", "title": "Acupuncture and sensorineural hearing loss: a review.", "content": "The use of acupuncture for treatment of sensorineural hearing impairment is a controversial subject among physicians and audiologists. Until recently, sufficient experimental data were not available to guide those who manage hearing-impaired children and adults. The purpose of this paper is to review current research evidence regarding the use of acupuncture technics for treating sensorineural hearing loss. In general, experimental evidence regarding such treatment is not encouraging. Patients should be advised of the questionable value of acupuncture for improving sensorineural auditory deficits.", "contents": "Acupuncture and sensorineural hearing loss: a review. The use of acupuncture for treatment of sensorineural hearing impairment is a controversial subject among physicians and audiologists. Until recently, sufficient experimental data were not available to guide those who manage hearing-impaired children and adults. The purpose of this paper is to review current research evidence regarding the use of acupuncture technics for treating sensorineural hearing loss. In general, experimental evidence regarding such treatment is not encouraging. Patients should be advised of the questionable value of acupuncture for improving sensorineural auditory deficits."} {"id": "PMID:1273619", "title": "Ectopic pregnancy: a review of 122 cases.", "content": "Ruptured ectopic pregnancy constitutes a major gynecologic emergency which may result in death. From 1965 through 1973, 122 patients with ectopic pregnancy were treated at Wilford Hall USAF Hospital. Diagnostic procedures, causative factors, and patient management are reviewed and discussed. The most common symptoms were pain (95%), amenorrhea (79%), and abnormal bleeding (76%). An adnexal mass was found in only 40% of the patients. The treatment of choice was salpingectomy, and there were no deaths in this group of patients.", "contents": "Ectopic pregnancy: a review of 122 cases. Ruptured ectopic pregnancy constitutes a major gynecologic emergency which may result in death. From 1965 through 1973, 122 patients with ectopic pregnancy were treated at Wilford Hall USAF Hospital. Diagnostic procedures, causative factors, and patient management are reviewed and discussed. The most common symptoms were pain (95%), amenorrhea (79%), and abnormal bleeding (76%). An adnexal mass was found in only 40% of the patients. The treatment of choice was salpingectomy, and there were no deaths in this group of patients."} {"id": "PMID:1273620", "title": "Technic of deep hypothermia and circulatory arrest in the neonate and infant.", "content": "Most congenital heart anomalies now can be surgically corrected in a neonate or very young infant. Because their hearts are so small, it is advantageous to work in a bloodless and motionless operative field. Deep hypothermia with circulatory arrest provides this setting. Physiologic problems associated with hypothermia are minimized by inducing general vasodilatation with large doses of methylprednisolone. Surface cooling is done with ice blankets and small sandwich bags filled with crushed ice. The patient's temperature gradually falls to 75.2 F (24 C). After median sternotomy, core cooling can be used to bring the patient's temperature to the desired 68 F (20 C). Circulatory arrest is produced by draining blood into the reservoir and cross-clamping the great vessels and venae cavae. It can be maintained for up to 60 minutes. In infants over six months and over 6 kg (13.2 lb), moderate hypothermia 77 F (25 C) and low perfusion (1/4-1/3 of normal) with short periods (10 to 15 minutes) of circulatory arrest improve operative conditions and allow correction of the most complicated congenital heart defects.", "contents": "Technic of deep hypothermia and circulatory arrest in the neonate and infant. Most congenital heart anomalies now can be surgically corrected in a neonate or very young infant. Because their hearts are so small, it is advantageous to work in a bloodless and motionless operative field. Deep hypothermia with circulatory arrest provides this setting. Physiologic problems associated with hypothermia are minimized by inducing general vasodilatation with large doses of methylprednisolone. Surface cooling is done with ice blankets and small sandwich bags filled with crushed ice. The patient's temperature gradually falls to 75.2 F (24 C). After median sternotomy, core cooling can be used to bring the patient's temperature to the desired 68 F (20 C). Circulatory arrest is produced by draining blood into the reservoir and cross-clamping the great vessels and venae cavae. It can be maintained for up to 60 minutes. In infants over six months and over 6 kg (13.2 lb), moderate hypothermia 77 F (25 C) and low perfusion (1/4-1/3 of normal) with short periods (10 to 15 minutes) of circulatory arrest improve operative conditions and allow correction of the most complicated congenital heart defects."} {"id": "PMID:1273621", "title": "Penetrating injuries of the laryngotracheal area.", "content": "Penetrating injuries of the laryngotracheal area require immediate maintenance of an adequate airway and prompt surgical exploration and repair. Two basic principles are illustrated by case reports: repairing major vessels before doing the laryngotracheal repair and using adjacent tissues to repair traumatic defects. We suggest a team approach at operation.", "contents": "Penetrating injuries of the laryngotracheal area. Penetrating injuries of the laryngotracheal area require immediate maintenance of an adequate airway and prompt surgical exploration and repair. Two basic principles are illustrated by case reports: repairing major vessels before doing the laryngotracheal repair and using adjacent tissues to repair traumatic defects. We suggest a team approach at operation."} {"id": "PMID:1273622", "title": "Liquid crystal thermography: a measure of therapeutic response to reserpine given intra-arterially.", "content": "Twelve patients with Raynaud's phenomenon secondary to acrosclerosis and/or systemic sclerosis were evaluated before and after intra-arterial administration of reserpine. The irridescent color changes seen with these liquid crystals support recent evidence for short-term effectiveness of reserpine given intra-arterially.", "contents": "Liquid crystal thermography: a measure of therapeutic response to reserpine given intra-arterially. Twelve patients with Raynaud's phenomenon secondary to acrosclerosis and/or systemic sclerosis were evaluated before and after intra-arterial administration of reserpine. The irridescent color changes seen with these liquid crystals support recent evidence for short-term effectiveness of reserpine given intra-arterially."} {"id": "PMID:1273623", "title": "Hypocalcemia as a complication of jejunoileal bypass for morbid obesity.", "content": "Hypocalcemia following jejunoileal bypass for morbid obesity is not an uncommon occurrence. Three cases of severe hypocalcemia after bypass operation are presented with emphasis on the altered physiology of calcium homeostasis. Recognition and treatment of bypass hypocalcemia can avert a potentially serious complication.", "contents": "Hypocalcemia as a complication of jejunoileal bypass for morbid obesity. Hypocalcemia following jejunoileal bypass for morbid obesity is not an uncommon occurrence. Three cases of severe hypocalcemia after bypass operation are presented with emphasis on the altered physiology of calcium homeostasis. Recognition and treatment of bypass hypocalcemia can avert a potentially serious complication."} {"id": "PMID:1273624", "title": "Influence of tidal volume and pulmonary artery occlusion on arterial oxygenation during endobronchial anesthesia.", "content": "Arterial blood gases, intrapulmonary right-to-left shunt, airway pressures, and systemic and pulmonary arterial pressures were studied in 20 patients ventilated through a double lumen endobronchial tube during thoracotomy. Inspired oxygen concentration was 98% to 100%. Blood samples for measurement of blood gases and oxygen content were obtained during ventilation of both lungs (VT 15 ml/kg), one lung (VT 15 ml/kg and 8 ml/kg), and after occlusion of the opposite pulmonary artery. Mean oxygen tensions fell significantly, from 310 mm Hg during two-lung ventilation to 155 during one-lung ventilation, and rose again to 280 after pulmonary artery occlusion. Corresponding mean shunt values rose from 25% to 34% of cardiac output and fell again to 25%. When VT was reduced, patients who had had low oxygen tensions (less than 150 mm Hg) at the higher volume showed an increase in PaO2, and conversely. Shunts changed accordingly. Even with this high FIO2, some patients had oxygen tensions of less than 80 mm Hg during lung collapse. PaO2 values during one-lung ventilation were significantly related to patients' preoperative oxygen tensions, as well as to those during two-lung ventilation. In view of the low arterial oxygen tensions found in some patients and the lack of absolute correlation of the PaO2 with tidal volume, an FIO2 of close to 1.0 is recommended during one-lung ventilation, along with frequent or continuous monitoring of the arterial PaO2.", "contents": "Influence of tidal volume and pulmonary artery occlusion on arterial oxygenation during endobronchial anesthesia. Arterial blood gases, intrapulmonary right-to-left shunt, airway pressures, and systemic and pulmonary arterial pressures were studied in 20 patients ventilated through a double lumen endobronchial tube during thoracotomy. Inspired oxygen concentration was 98% to 100%. Blood samples for measurement of blood gases and oxygen content were obtained during ventilation of both lungs (VT 15 ml/kg), one lung (VT 15 ml/kg and 8 ml/kg), and after occlusion of the opposite pulmonary artery. Mean oxygen tensions fell significantly, from 310 mm Hg during two-lung ventilation to 155 during one-lung ventilation, and rose again to 280 after pulmonary artery occlusion. Corresponding mean shunt values rose from 25% to 34% of cardiac output and fell again to 25%. When VT was reduced, patients who had had low oxygen tensions (less than 150 mm Hg) at the higher volume showed an increase in PaO2, and conversely. Shunts changed accordingly. Even with this high FIO2, some patients had oxygen tensions of less than 80 mm Hg during lung collapse. PaO2 values during one-lung ventilation were significantly related to patients' preoperative oxygen tensions, as well as to those during two-lung ventilation. In view of the low arterial oxygen tensions found in some patients and the lack of absolute correlation of the PaO2 with tidal volume, an FIO2 of close to 1.0 is recommended during one-lung ventilation, along with frequent or continuous monitoring of the arterial PaO2."} {"id": "PMID:1273625", "title": "Fractures of the hip in childhood.", "content": "Twenty hip fractures in 19 children aged 2 1/2 to 18 were analyzed in a ten-year retrospective review at the University of Alabama Hospitals in Birmingham, Ala. There was one epiphyseal, one intertrochanteric, 4 subtrochanteric, and 14 intracapsular fractures. The mechanism of injury was usually severe trauma with 31% of the patients sustaining other associated major injuries. Avascular necrosis occurred in three intracapsular fractures (23%), all seemingly related to inadequate internal fixation. Coxa vara occurred in 30% of the patients; all were treated by closed methods, and delayed union and nonunion occurred in 10% of the series. Nine patients developed discrepancies of limb length between 1/2 and 13/4 inches. It was thought that intracapsular fractures should be treated with prompt open reduction and internal fixation with multiple pins; whereas, extracapsular fractures may be treated by either open or closed methods.", "contents": "Fractures of the hip in childhood. Twenty hip fractures in 19 children aged 2 1/2 to 18 were analyzed in a ten-year retrospective review at the University of Alabama Hospitals in Birmingham, Ala. There was one epiphyseal, one intertrochanteric, 4 subtrochanteric, and 14 intracapsular fractures. The mechanism of injury was usually severe trauma with 31% of the patients sustaining other associated major injuries. Avascular necrosis occurred in three intracapsular fractures (23%), all seemingly related to inadequate internal fixation. Coxa vara occurred in 30% of the patients; all were treated by closed methods, and delayed union and nonunion occurred in 10% of the series. Nine patients developed discrepancies of limb length between 1/2 and 13/4 inches. It was thought that intracapsular fractures should be treated with prompt open reduction and internal fixation with multiple pins; whereas, extracapsular fractures may be treated by either open or closed methods."} {"id": "PMID:1273626", "title": "Medium and long chain serum free fatty acids in a case of Reye's syndrome.", "content": "Elevated serum free fatty acids (FFA) have been implicated previously as the agent causing encephalopathy and fatty degeneration of the viscera (Reye's syndrome). This study documents a decrease in medium and long chain FFA from elevated levels (1.35 mEq/liter) to low levels (0.30 mEq/liter) in a patient successfully treated with exchange transfusions.", "contents": "Medium and long chain serum free fatty acids in a case of Reye's syndrome. Elevated serum free fatty acids (FFA) have been implicated previously as the agent causing encephalopathy and fatty degeneration of the viscera (Reye's syndrome). This study documents a decrease in medium and long chain FFA from elevated levels (1.35 mEq/liter) to low levels (0.30 mEq/liter) in a patient successfully treated with exchange transfusions."} {"id": "PMID:1273628", "title": "Minimal brain dysfunction/specific learning disability: a clinical approach for the primary physician.", "content": "Minimal brain dysfunction is a neurodevelopmental disorder which can be found in nearly 20% of school children. It is characterized by evidences of immaturity involving control of activity, emotions, and behavior, and by specific learning disabilities involving the communicating skills needed in reading, writing, and mathematics. The prime deficits in the classroom are an inability to maintain attention and concentration and an inability to skillfully blend the auditory and visual functions essential in language performance. Medical evaluation will reveal many of the \"soft signs\" of neurologic involvement, and educational appraisal will indicate a wide scatter in testing scores with a marked discrepancy between evaluated potential and actual classroom achievement. Remedial efforts directed at early detection, relief from pressure and unjust punishment or ridicule from parents and teachers, and adjustment of the educational environment with consideration of the child's individual talents, combined with the judicious use of medications to prolong attention span and improve neurodevelopmental maturity, hold promise of improving the lot of most involved children. There are valid indications that expansion of such programs can do much to prevent these youngsters from developing severe personality maladjustment and delinquent behavior, as well as emotional illness in later life.", "contents": "Minimal brain dysfunction/specific learning disability: a clinical approach for the primary physician. Minimal brain dysfunction is a neurodevelopmental disorder which can be found in nearly 20% of school children. It is characterized by evidences of immaturity involving control of activity, emotions, and behavior, and by specific learning disabilities involving the communicating skills needed in reading, writing, and mathematics. The prime deficits in the classroom are an inability to maintain attention and concentration and an inability to skillfully blend the auditory and visual functions essential in language performance. Medical evaluation will reveal many of the \"soft signs\" of neurologic involvement, and educational appraisal will indicate a wide scatter in testing scores with a marked discrepancy between evaluated potential and actual classroom achievement. Remedial efforts directed at early detection, relief from pressure and unjust punishment or ridicule from parents and teachers, and adjustment of the educational environment with consideration of the child's individual talents, combined with the judicious use of medications to prolong attention span and improve neurodevelopmental maturity, hold promise of improving the lot of most involved children. There are valid indications that expansion of such programs can do much to prevent these youngsters from developing severe personality maladjustment and delinquent behavior, as well as emotional illness in later life."} {"id": "PMID:1273711", "title": "Isoniazid inactivation in Black patients with tuberculosis.", "content": "A 27% incidence of slow INH inactivator (acetylator) status was observed in a group of 100 Black tuberculotic patients. It is suggested that the incidence of INH toxicity may be high in this group of patients and that clinical cognisance of this problem is desirable.", "contents": "Isoniazid inactivation in Black patients with tuberculosis. A 27% incidence of slow INH inactivator (acetylator) status was observed in a group of 100 Black tuberculotic patients. It is suggested that the incidence of INH toxicity may be high in this group of patients and that clinical cognisance of this problem is desirable."} {"id": "PMID:1273712", "title": "Immunological studies in children with chronic pulmonary infection.", "content": "Twenty-three children with chronic pulmonary symptoms following acute lower respiratory tract infection were investigated with a view to establishing their immune status. Cell-mediated immunity was depressed in the majority. Serial testing over some months showed improvement in some and fluctuation or non-recovery in others. The leucocyte function, gamma-globulin and immunoglobulin levels were normal.", "contents": "Immunological studies in children with chronic pulmonary infection. Twenty-three children with chronic pulmonary symptoms following acute lower respiratory tract infection were investigated with a view to establishing their immune status. Cell-mediated immunity was depressed in the majority. Serial testing over some months showed improvement in some and fluctuation or non-recovery in others. The leucocyte function, gamma-globulin and immunoglobulin levels were normal."} {"id": "PMID:1273713", "title": "Placental lactogen in pregnant Natal Indian diabetic patients.", "content": "The plasma levels of human placental lactogen (HPL) in healthy and in diabetic pregnant Natal Indians were studied. The plasma HPL pattern in the control group was similar to that recorded in the literature and reconfirmed the increase in HPL during normal pregnancy. The plasma HPL of the pregnant diabetics was usually within 1 standard deviation of the mean normal value for that duration of pregnancy. HPL excess could not be incriminated as a cause for the disturbed metabolism in the women with diabetes.", "contents": "Placental lactogen in pregnant Natal Indian diabetic patients. The plasma levels of human placental lactogen (HPL) in healthy and in diabetic pregnant Natal Indians were studied. The plasma HPL pattern in the control group was similar to that recorded in the literature and reconfirmed the increase in HPL during normal pregnancy. The plasma HPL of the pregnant diabetics was usually within 1 standard deviation of the mean normal value for that duration of pregnancy. HPL excess could not be incriminated as a cause for the disturbed metabolism in the women with diabetes."} {"id": "PMID:1273714", "title": "A Poisons Reference Centre for children.", "content": "A statistical analysis of poisoning cases treated at the Red Cross Children's Hospital is presented. The organisation and functioning of the Poisons Reference Centre is described and an analysis made of the poison ingestions reported to the Centre.", "contents": "A Poisons Reference Centre for children. A statistical analysis of poisoning cases treated at the Red Cross Children's Hospital is presented. The organisation and functioning of the Poisons Reference Centre is described and an analysis made of the poison ingestions reported to the Centre."} {"id": "PMID:1273715", "title": "Defective bicarbonate secretion in response to duodenal acidification in patients with chronic gastric or duodenal ulceration.", "content": "Histamine infusion studies were performed in 54 healthy persons, in 58 patients with duodenal ulcers and in 29 patients with gastric ulcers. The acid load entering the duodenum was estimated by measuring the loss of an intragastric marker, phenol red. The volume of duodenal juice that had refluxed into the stomach and which was aspirated with the gastric juice was estimated by the sodium content of the aspirate. The bicarbonate concentration of the refluxed duodenal juice was calculated from the relationship between neutralisation and total electrolyte concentration, since the reaction of one bicarbonate ion removes two ions from the resultant mixture. The mean bicarbonate concentration of the refluxed duodenal juice in the control group was 116,4 (+/- 9) mEq/1, and the individual bicarbonate concentrations showed the expected dependence on the magnitude of the intraduodenal acid load. The mean bicarbonate concentration in patients with duodenal ulcers was 84,6 (+/- 9) mEq/1, which was significantly lower than in healthy persons. In patients with duodenal ulcers and in those with gastric ulcers, the reflux bicarbonate concentrations were independent of acid load. These results confirm previous reports of an impaired pancreatic bicarbonate secretion in response to duodenal acid load in patients with duodenal ulcers, and indicate a similar response in patients with gastric ulcers.", "contents": "Defective bicarbonate secretion in response to duodenal acidification in patients with chronic gastric or duodenal ulceration. Histamine infusion studies were performed in 54 healthy persons, in 58 patients with duodenal ulcers and in 29 patients with gastric ulcers. The acid load entering the duodenum was estimated by measuring the loss of an intragastric marker, phenol red. The volume of duodenal juice that had refluxed into the stomach and which was aspirated with the gastric juice was estimated by the sodium content of the aspirate. The bicarbonate concentration of the refluxed duodenal juice was calculated from the relationship between neutralisation and total electrolyte concentration, since the reaction of one bicarbonate ion removes two ions from the resultant mixture. The mean bicarbonate concentration of the refluxed duodenal juice in the control group was 116,4 (+/- 9) mEq/1, and the individual bicarbonate concentrations showed the expected dependence on the magnitude of the intraduodenal acid load. The mean bicarbonate concentration in patients with duodenal ulcers was 84,6 (+/- 9) mEq/1, which was significantly lower than in healthy persons. In patients with duodenal ulcers and in those with gastric ulcers, the reflux bicarbonate concentrations were independent of acid load. These results confirm previous reports of an impaired pancreatic bicarbonate secretion in response to duodenal acid load in patients with duodenal ulcers, and indicate a similar response in patients with gastric ulcers."} {"id": "PMID:1273716", "title": "Oesophageal atresia and tracheo-oesophageal fistula.", "content": "The operative management of oesophageal atresia is reviewed. The operative technique and the approach to management, based on antomical classification of oesophageal atresia and classification into 3 different risk groups, are stressed. The embryology, aetiology, clinical features, symptoms and signs and radiological diagnosis of this condition are also briefly discussed.", "contents": "Oesophageal atresia and tracheo-oesophageal fistula. The operative management of oesophageal atresia is reviewed. The operative technique and the approach to management, based on antomical classification of oesophageal atresia and classification into 3 different risk groups, are stressed. The embryology, aetiology, clinical features, symptoms and signs and radiological diagnosis of this condition are also briefly discussed."} {"id": "PMID:1273721", "title": "Emergency management of acute myocardial infarction by the general practitioner.", "content": "In the Cape GP Emergency Coronary Care Project, 129 general practitioners (GPs) collaborated over a 14-month period. The objectives were to reach all patients with symptoms of acute myocardial infarction as promptly as possible, and to institute therapy according to a simple protocol, where the emphasis was on the prophylactic administration of antidysrhythmic drugs. The results showed that 38% of a total of 333 patients received treatment within 1 hour of the onset of their symptoms, and 75% within 4 hours. The mortality at the end of 1 month was 15% in 333 patients of all ages, and 10,7% for 272 under the age of 70 years. The over-all community death rate from coronary heart disease in the patients of the participating GPs was 28,3% in 445 patients of all ages, and 23,3% in 356 patients under 70 years of age. These death rates are well below those reported in other comparable series. There was a low incidence of arrhythmic death, and only 1 death among patients who had received appropriate antidysrhythmic therapy. No ill-effects of complications occurred after the routine prophylactic administration of antidysrhythmic drugs. It is concluded that in the prehospital phase of acute myocardial infarciton, the Cape GPs were able to administer a service which compared favourably with that of a mobile intensive coronary care unit, at almost no extra cost to the community, and with very little extra strain on their practices.", "contents": "Emergency management of acute myocardial infarction by the general practitioner. In the Cape GP Emergency Coronary Care Project, 129 general practitioners (GPs) collaborated over a 14-month period. The objectives were to reach all patients with symptoms of acute myocardial infarction as promptly as possible, and to institute therapy according to a simple protocol, where the emphasis was on the prophylactic administration of antidysrhythmic drugs. The results showed that 38% of a total of 333 patients received treatment within 1 hour of the onset of their symptoms, and 75% within 4 hours. The mortality at the end of 1 month was 15% in 333 patients of all ages, and 10,7% for 272 under the age of 70 years. The over-all community death rate from coronary heart disease in the patients of the participating GPs was 28,3% in 445 patients of all ages, and 23,3% in 356 patients under 70 years of age. These death rates are well below those reported in other comparable series. There was a low incidence of arrhythmic death, and only 1 death among patients who had received appropriate antidysrhythmic therapy. No ill-effects of complications occurred after the routine prophylactic administration of antidysrhythmic drugs. It is concluded that in the prehospital phase of acute myocardial infarciton, the Cape GPs were able to administer a service which compared favourably with that of a mobile intensive coronary care unit, at almost no extra cost to the community, and with very little extra strain on their practices."} {"id": "PMID:1273722", "title": "Splenectomy and myelofibrosis.", "content": "Two patients are reported in whom splenectomy during the course of myelofibrosis was followed by rapid deterioration in the function of a previously involved liver, and was characterised by refractory ascites, increasing jaundice, and death. It is important to recognise this complication, since ectopic haematopoiesis can be demonstrated on liver biopsy and, perhaps, controlled with radiotherapy or cytotoxic chemotherapy.", "contents": "Splenectomy and myelofibrosis. Two patients are reported in whom splenectomy during the course of myelofibrosis was followed by rapid deterioration in the function of a previously involved liver, and was characterised by refractory ascites, increasing jaundice, and death. It is important to recognise this complication, since ectopic haematopoiesis can be demonstrated on liver biopsy and, perhaps, controlled with radiotherapy or cytotoxic chemotherapy."} {"id": "PMID:1273723", "title": "Pneumopericardium complicating amoebic liver abscess. A case report.", "content": "Pneumopericardium arises most commonly as a result of a bronchial or oesophageal neoplasm which erodes the pericardial cavity. A case of pneumopericardium associated with amoebic liver abscess, a complication of invasive amoebiasis not previously reported, is described.", "contents": "Pneumopericardium complicating amoebic liver abscess. A case report. Pneumopericardium arises most commonly as a result of a bronchial or oesophageal neoplasm which erodes the pericardial cavity. A case of pneumopericardium associated with amoebic liver abscess, a complication of invasive amoebiasis not previously reported, is described."} {"id": "PMID:1273724", "title": "Focal dermal hypoplasia (Goltz syndrome) in a male. A case report.", "content": "A 3-year-old boy presented with the clinical and histological features of focal dermal hypoplasia. Radiological examination showed the longitudinal parallel striations of osteopathia striata. As far as can be ascertained this is the fifth recorded case in a male patient.", "contents": "Focal dermal hypoplasia (Goltz syndrome) in a male. A case report. A 3-year-old boy presented with the clinical and histological features of focal dermal hypoplasia. Radiological examination showed the longitudinal parallel striations of osteopathia striata. As far as can be ascertained this is the fifth recorded case in a male patient."} {"id": "PMID:1273726", "title": "Late deaths from endometrial carcinoma.", "content": "An analysis has been made of all the patients with endometrial carcinoma who were seen in our department between 1959 and 1968. A total of 155 patients with a minimum follow-up period of 5 years were evaluated. About 20% of the patients who die, do so more than 5 years after diagnosis and treatment of the primary cancer. A disconcertingly high incidence of death from active tumours is found when patients are followed up for long enough, i.e. 1 in 3 patients who do not die of intercurrent disease. Late deaths are even caused by poorly-differentiated tumours, and also by haematogenous spread. When the results of different treatment regimens are compared, it will thus be necessary to take 10-year survival rates into account.", "contents": "Late deaths from endometrial carcinoma. An analysis has been made of all the patients with endometrial carcinoma who were seen in our department between 1959 and 1968. A total of 155 patients with a minimum follow-up period of 5 years were evaluated. About 20% of the patients who die, do so more than 5 years after diagnosis and treatment of the primary cancer. A disconcertingly high incidence of death from active tumours is found when patients are followed up for long enough, i.e. 1 in 3 patients who do not die of intercurrent disease. Late deaths are even caused by poorly-differentiated tumours, and also by haematogenous spread. When the results of different treatment regimens are compared, it will thus be necessary to take 10-year survival rates into account."} {"id": "PMID:1273727", "title": "[Radiology in cases of trauma--an obligatory investigation].", "content": "The radiology of trauma is of increasing importance in South Africa, where the treatment of victims of motor accidents forms a major part of emergency medical practice. All practitioners should be aware of the medical and legal obligations that they have to fulfil in this investigation, which nowadays is regarded as part of clinical medicine. The most important principles in the radiology of trauma are briefly discussed.", "contents": "[Radiology in cases of trauma--an obligatory investigation]. The radiology of trauma is of increasing importance in South Africa, where the treatment of victims of motor accidents forms a major part of emergency medical practice. All practitioners should be aware of the medical and legal obligations that they have to fulfil in this investigation, which nowadays is regarded as part of clinical medicine. The most important principles in the radiology of trauma are briefly discussed."} {"id": "PMID:1273728", "title": "Osseous manifestations of congenital syphilis.", "content": "The re-emergence of syphilis as a medical problem in most parts of the world makes it necessary to reinstate the congenital osseous manifestations as an important element in the differential diagnosis of the disease in infancy. The previously well-known snuffles, pseudoparalysis and bizarre radiological changes should now be brought to the attention of perhaps more than one generation of physicians who underwent their medical training at the time when the disease was a rarity.", "contents": "Osseous manifestations of congenital syphilis. The re-emergence of syphilis as a medical problem in most parts of the world makes it necessary to reinstate the congenital osseous manifestations as an important element in the differential diagnosis of the disease in infancy. The previously well-known snuffles, pseudoparalysis and bizarre radiological changes should now be brought to the attention of perhaps more than one generation of physicians who underwent their medical training at the time when the disease was a rarity."} {"id": "PMID:1273730", "title": "Lipotoma of the breast diagnosed by film and xeromammography.", "content": "Five cases of the relatively uncommon intramammary lipoma and 4 cases of the rare adenolipoma were found in more than 5,000 patients who underwent mammography. The mammographic features of the intramammary and paramammary lipomata are given and the characteristic xeroradiographic appearance of adenolipomata is described. The 4 adenolipomata were only visualised by xeroradiography. The reason for these neoplasms being visible on xerograms and not on film mammograms is not clear, but we surmise that it is owing to the 'edge enhancement' phenomenon inherent in the xeroradiographic process. The question whether adenolipomata of the breast are true invasive tumours or mixed neoplasms is discussed.", "contents": "Lipotoma of the breast diagnosed by film and xeromammography. Five cases of the relatively uncommon intramammary lipoma and 4 cases of the rare adenolipoma were found in more than 5,000 patients who underwent mammography. The mammographic features of the intramammary and paramammary lipomata are given and the characteristic xeroradiographic appearance of adenolipomata is described. The 4 adenolipomata were only visualised by xeroradiography. The reason for these neoplasms being visible on xerograms and not on film mammograms is not clear, but we surmise that it is owing to the 'edge enhancement' phenomenon inherent in the xeroradiographic process. The question whether adenolipomata of the breast are true invasive tumours or mixed neoplasms is discussed."} {"id": "PMID:1273731", "title": "Insulin secretion in pregnant diabetic Indian women in Natal.", "content": "A study was undertaken to establish the plasma insulin response to an oral glucose load of 100 g in pregnant diabetic Indian women living in Natal. Eighty-three patients were investigated during the second and third trimesters of pregnancy and during the postpartum period. Although absolute mean plasma insulin values were lower than those found in non-diabetic controls, these patients exhibited compensatory hyperinsulinism typical of late pregnancy. This feature is not present in juvenile onset pregnant diabetic women. Metabolic control of the diabetic syndrome by insulin therapy is mandatory in the latter patients, whereas the former usually respond to the beta cell-stimulating sulphonylureas throughout pregnancy.", "contents": "Insulin secretion in pregnant diabetic Indian women in Natal. A study was undertaken to establish the plasma insulin response to an oral glucose load of 100 g in pregnant diabetic Indian women living in Natal. Eighty-three patients were investigated during the second and third trimesters of pregnancy and during the postpartum period. Although absolute mean plasma insulin values were lower than those found in non-diabetic controls, these patients exhibited compensatory hyperinsulinism typical of late pregnancy. This feature is not present in juvenile onset pregnant diabetic women. Metabolic control of the diabetic syndrome by insulin therapy is mandatory in the latter patients, whereas the former usually respond to the beta cell-stimulating sulphonylureas throughout pregnancy."} {"id": "PMID:1273732", "title": "Insulin secretion in healthy pregnant Natal Indians.", "content": "The pattern of insulin release in healthy pregnant Natal Indian women was determined. Progressive hyperinsulinaemia associated with advancing pregnancy was confirmed, together with evidence of a decreased sensitivity to insulin at a cellular level. The plasma insulin response returned to normal in the early puerperium.", "contents": "Insulin secretion in healthy pregnant Natal Indians. The pattern of insulin release in healthy pregnant Natal Indian women was determined. Progressive hyperinsulinaemia associated with advancing pregnancy was confirmed, together with evidence of a decreased sensitivity to insulin at a cellular level. The plasma insulin response returned to normal in the early puerperium."} {"id": "PMID:1273733", "title": "Excessive Siamese twinning in Southern Africa.", "content": "Twelve sets of conjoined twins have been born in Southern Africa since February 1974. This possibly represents a significant increase in the incidence of Siamese twinning and may be the result of unknown environmental agents. Several of the sets of twins were diagnosed antenatally. In view of the current circumstances a high index of suspicion is probably justified in the presence of maternal hydramnios or fetal malpresentation.", "contents": "Excessive Siamese twinning in Southern Africa. Twelve sets of conjoined twins have been born in Southern Africa since February 1974. This possibly represents a significant increase in the incidence of Siamese twinning and may be the result of unknown environmental agents. Several of the sets of twins were diagnosed antenatally. In view of the current circumstances a high index of suspicion is probably justified in the presence of maternal hydramnios or fetal malpresentation."} {"id": "PMID:1273734", "title": "Induction of labour with oral prostaglandin E2.", "content": "Oral prostaglandin E2 was used for inducing labour in 37 patients without initial rupture of membranes. Two dosage regimens were used: in the one 0.5 mg of oral PGE2 was given hourly, and in the other the dose of oral PGE2 was doubled hourly, starting with a dose of 0,5 mg and increasing to a maximum single dose of 2,0 mg. The incremental dosage regimen was found to be more successful in inducing labour than the constant dosage regimen. The success rate was 94,95%. Side-effects were found to occur rarely and to be dose-related. Fetal distress did not occur in this study.", "contents": "Induction of labour with oral prostaglandin E2. Oral prostaglandin E2 was used for inducing labour in 37 patients without initial rupture of membranes. Two dosage regimens were used: in the one 0.5 mg of oral PGE2 was given hourly, and in the other the dose of oral PGE2 was doubled hourly, starting with a dose of 0,5 mg and increasing to a maximum single dose of 2,0 mg. The incremental dosage regimen was found to be more successful in inducing labour than the constant dosage regimen. The success rate was 94,95%. Side-effects were found to occur rarely and to be dose-related. Fetal distress did not occur in this study."} {"id": "PMID:1273735", "title": "Aorto-oesophageal fistula complicating tuberculous aortitis. A case report.", "content": "A case of massive upper gastro-intestinal haemorrhage in a Black woman owing to tuberculous aorto-oesophageal fistula is reported. The literature is reviewed and the clinical presentation discussed. This possibly represents only the second case of aorto-oesophageal fistula complicating postprimary tuberculosis to appear in medical literature.", "contents": "Aorto-oesophageal fistula complicating tuberculous aortitis. A case report. A case of massive upper gastro-intestinal haemorrhage in a Black woman owing to tuberculous aorto-oesophageal fistula is reported. The literature is reviewed and the clinical presentation discussed. This possibly represents only the second case of aorto-oesophageal fistula complicating postprimary tuberculosis to appear in medical literature."} {"id": "PMID:1273736", "title": "Scalp ringworm among Black children in South Africa and the occurrence of Trichophyton yaoundei.", "content": "The prevalence of tinea capitis among 153 children who were selected by overt signs of scalp infestation from among 658 Black schoolchildren, was studied in two rural areas of the Transvaal. In both areas (Eastern and Northern Transvaal), Trichophyton violaceum was the predominant dermatophyte species which was isolated. Microsporum audouinii was isolated in both areas from a total of 4 children, but M. canis was the cause of only 1 infection, and that was in the Eastern Transvaal. Five infections caused by T. yaoundei, all of which occurred in the Northern Transvaal, were recorded. They are the first documented cases of endothrix scalp ringworm caused by this species in South Africa.", "contents": "Scalp ringworm among Black children in South Africa and the occurrence of Trichophyton yaoundei. The prevalence of tinea capitis among 153 children who were selected by overt signs of scalp infestation from among 658 Black schoolchildren, was studied in two rural areas of the Transvaal. In both areas (Eastern and Northern Transvaal), Trichophyton violaceum was the predominant dermatophyte species which was isolated. Microsporum audouinii was isolated in both areas from a total of 4 children, but M. canis was the cause of only 1 infection, and that was in the Eastern Transvaal. Five infections caused by T. yaoundei, all of which occurred in the Northern Transvaal, were recorded. They are the first documented cases of endothrix scalp ringworm caused by this species in South Africa."} {"id": "PMID:1273737", "title": "Angio-immunoblastic lymphadenopathy. A report of 3 cases.", "content": "Angio-immunoblastic lymphadenopathy (AILD) was diagnosed in 3 Black patients, AILD is a non-malignant disorder which resembles a malignant lymphoma clinically and morphologically. It is thought to represent an abnormal response of B lymphocytes to antigenic stimuli which are often therapeutic agents. The disorder usually affects adults of the older age group and the clinical course can be rapidly fatal, particularly if vigorous chemotherapy is given. Of the 3 patients with AILD, 2 died from complicating infections within 6 months after the initial diagnosis. The third patient was completely cured after short courses of prednisone and vincristine. It appears that in some patients the disorder may be completely reversible but whether these patients are at a greater risk of eventually developing a lymphoma is uncertain at the present time, and remains to be ascertained by their long-term follow-up.", "contents": "Angio-immunoblastic lymphadenopathy. A report of 3 cases. Angio-immunoblastic lymphadenopathy (AILD) was diagnosed in 3 Black patients, AILD is a non-malignant disorder which resembles a malignant lymphoma clinically and morphologically. It is thought to represent an abnormal response of B lymphocytes to antigenic stimuli which are often therapeutic agents. The disorder usually affects adults of the older age group and the clinical course can be rapidly fatal, particularly if vigorous chemotherapy is given. Of the 3 patients with AILD, 2 died from complicating infections within 6 months after the initial diagnosis. The third patient was completely cured after short courses of prednisone and vincristine. It appears that in some patients the disorder may be completely reversible but whether these patients are at a greater risk of eventually developing a lymphoma is uncertain at the present time, and remains to be ascertained by their long-term follow-up."} {"id": "PMID:1273738", "title": "[Carcinoma of Vater's ampulla diagnosed by operative cholangiography: a case report].", "content": "A case is reported in which carcinoma of the ampulla of Vater was diagnosed during operation by means of routine cholangiography.", "contents": "[Carcinoma of Vater's ampulla diagnosed by operative cholangiography: a case report]. A case is reported in which carcinoma of the ampulla of Vater was diagnosed during operation by means of routine cholangiography."} {"id": "PMID:1273741", "title": "The influence of lateral tilt on limb blood flow in advanced pregnancy.", "content": "Blood flow of the forearm and calf were measured in 20 expectant mothers by means of strain gauge plethysmography. Measurements were made with the patients initially lying supine, then tilted to the right or left side with a 15 degrees foam rubber wedge and, finally, after returning the subjects to the supine position. Blood flow of the forearm was unaltered by changes in maternal posture. Lower limb perfusion usually increased significantly when the mothers assumed the right or left lateral tilt position, and decreased when the patients again lay supine. The significance of these findings in relationship to aortocaval occlusion by the gravid uterus is discussed. We conclude that lateral tilt of the patient during Caesarean section should contribute significantly to the safety and welfare of both mother and infant.", "contents": "The influence of lateral tilt on limb blood flow in advanced pregnancy. Blood flow of the forearm and calf were measured in 20 expectant mothers by means of strain gauge plethysmography. Measurements were made with the patients initially lying supine, then tilted to the right or left side with a 15 degrees foam rubber wedge and, finally, after returning the subjects to the supine position. Blood flow of the forearm was unaltered by changes in maternal posture. Lower limb perfusion usually increased significantly when the mothers assumed the right or left lateral tilt position, and decreased when the patients again lay supine. The significance of these findings in relationship to aortocaval occlusion by the gravid uterus is discussed. We conclude that lateral tilt of the patient during Caesarean section should contribute significantly to the safety and welfare of both mother and infant."} {"id": "PMID:1273742", "title": "Tuberculous renal artery aneurysm: a case report.", "content": "Tuberculous renal artery aneurysm in a 36-year-old Black man is reported. This is thought to be the first case reported in the English language medical literature. The literature is reviewed with regard to presentation and management of renal artery aneurysm in general, with specific reference to tuberculous arterial infection.", "contents": "Tuberculous renal artery aneurysm: a case report. Tuberculous renal artery aneurysm in a 36-year-old Black man is reported. This is thought to be the first case reported in the English language medical literature. The literature is reviewed with regard to presentation and management of renal artery aneurysm in general, with specific reference to tuberculous arterial infection."} {"id": "PMID:1273743", "title": "[Giant cell tumor (osteoclastoma): a case report].", "content": "The history is presented of a 21-year-old woman with an osteoclastoma (giant cell tumour) which was treated with total local excision and an elbow prosthesis. A 5-year follow-up report, the problems of treatment and the different grades of malignancy, are discussed briefly, and the value of histological grading is shown.", "contents": "[Giant cell tumor (osteoclastoma): a case report]. The history is presented of a 21-year-old woman with an osteoclastoma (giant cell tumour) which was treated with total local excision and an elbow prosthesis. A 5-year follow-up report, the problems of treatment and the different grades of malignancy, are discussed briefly, and the value of histological grading is shown."} {"id": "PMID:1273744", "title": "The bonds of behaviour.", "content": "Of all the theories purporting to uncover the roots of childhood behaviour and its extension into adult behaviour, the most cogent relates to the physical and psychological bonds of attachment between infant and mother. It is helpful to divide the human lifespan into three periods, each of which has alternating phases of attachment and detachment.", "contents": "The bonds of behaviour. Of all the theories purporting to uncover the roots of childhood behaviour and its extension into adult behaviour, the most cogent relates to the physical and psychological bonds of attachment between infant and mother. It is helpful to divide the human lifespan into three periods, each of which has alternating phases of attachment and detachment."} {"id": "PMID:1273746", "title": "Post-traumatic intestinal obstruction.", "content": "The roentgenographic and pathologic findings in three patients with delayed post-traumatic intestinal obstruction are described. The pertinent literature also is reviewed to delineate the variable pathophysiology of the clinical phenomenon. As a result of the increasing incidence of blunt trauma in our society, the problem of occult intra-abdominal injury resulting in subsequent clinical disease always should be considered in the differential diagnosis of patients presenting later with intestinal complaints. Once considered, routine roentgenologic evaluation usually is diagnostic, and arteriographic evaluation should be considered if the diagnosis is strongly suspected in the face of normal contrast studies. If intestinal obstruction is diagnosed, operative treatment is indicated, simple, and effective.", "contents": "Post-traumatic intestinal obstruction. The roentgenographic and pathologic findings in three patients with delayed post-traumatic intestinal obstruction are described. The pertinent literature also is reviewed to delineate the variable pathophysiology of the clinical phenomenon. As a result of the increasing incidence of blunt trauma in our society, the problem of occult intra-abdominal injury resulting in subsequent clinical disease always should be considered in the differential diagnosis of patients presenting later with intestinal complaints. Once considered, routine roentgenologic evaluation usually is diagnostic, and arteriographic evaluation should be considered if the diagnosis is strongly suspected in the face of normal contrast studies. If intestinal obstruction is diagnosed, operative treatment is indicated, simple, and effective."} {"id": "PMID:1273747", "title": "Clinical experience with modified human umbilical cord vein for arterial bypass.", "content": "Umbilical veins were removed from human cords, tanned with gluteraldehyde, and surrounded by a polyester fiber mesh. Arterial bypasses were performed with this material in eight persons with threatened limb loss and for whom no other graft material was available. The distal anastomoses were to the small vessels of the leg or to the popliteal artery below the knee. Limb salvage and function were obtained in five patients. Three of these also required early thrombectomy to obtain success. This complication may be related to the presence of gluteraldehyde oligomers and polymers of free aldehyde groups. Morphologic evaluation of the graft suggests that human umbilical cords are a potentially valuable source for vascular substitutes.", "contents": "Clinical experience with modified human umbilical cord vein for arterial bypass. Umbilical veins were removed from human cords, tanned with gluteraldehyde, and surrounded by a polyester fiber mesh. Arterial bypasses were performed with this material in eight persons with threatened limb loss and for whom no other graft material was available. The distal anastomoses were to the small vessels of the leg or to the popliteal artery below the knee. Limb salvage and function were obtained in five patients. Three of these also required early thrombectomy to obtain success. This complication may be related to the presence of gluteraldehyde oligomers and polymers of free aldehyde groups. Morphologic evaluation of the graft suggests that human umbilical cords are a potentially valuable source for vascular substitutes."} {"id": "PMID:1273748", "title": "The optimal level of anticoagulation for decreasing experimental metastases.", "content": "Anticoagulation with warfarin is effective in decreasing experimental metastases, presumably by preventing the fibrin coagulum demonstrated to be necessary for the lodging of tumor cells. To determine the optimal level of anticoagulation for maximal antimetastatic effect, two similar experiments were completed with a methylcholanthrene-induced sarcoma in C57Bl mice. Footpad tumors were produced by tumor cell injection and the mice were divided into four equal groups: control, and groups on 1, 2, and 3 mg. per liter of warfarin, respectively. Control and anticoagulated mice were amputated at the same interval. Three weeks after amputation, all were killed and their metastases were quantitated. Prothrombin times ranged from 10 seconds in the control to 30 seconds in the 3 mg. per liter group. In Experiment 1, there was a significant reduction of pulmonary metastases at all levels of anticoagulation. The controls showed a mean number of 7.7 metastases per mouse, as compared to 2.9 (p less than 0.002) at 1 mg. per liter, 2.1 (p less than 0.0035) at 2 mg. per liter, and 0.7 (p less than 0.002) at 3 mg. per liter. In Experiment 2, the significant effect was found only at the 3 mg. per liter dose, with those mice having 2.3 metastases per mouse as compared with 5.5 in the controls (p less than 0.0001). We conclude that full anticoagulation in the range of 2.5 to 3 times normal is required for a maximal antimetastatic effect.", "contents": "The optimal level of anticoagulation for decreasing experimental metastases. Anticoagulation with warfarin is effective in decreasing experimental metastases, presumably by preventing the fibrin coagulum demonstrated to be necessary for the lodging of tumor cells. To determine the optimal level of anticoagulation for maximal antimetastatic effect, two similar experiments were completed with a methylcholanthrene-induced sarcoma in C57Bl mice. Footpad tumors were produced by tumor cell injection and the mice were divided into four equal groups: control, and groups on 1, 2, and 3 mg. per liter of warfarin, respectively. Control and anticoagulated mice were amputated at the same interval. Three weeks after amputation, all were killed and their metastases were quantitated. Prothrombin times ranged from 10 seconds in the control to 30 seconds in the 3 mg. per liter group. In Experiment 1, there was a significant reduction of pulmonary metastases at all levels of anticoagulation. The controls showed a mean number of 7.7 metastases per mouse, as compared to 2.9 (p less than 0.002) at 1 mg. per liter, 2.1 (p less than 0.0035) at 2 mg. per liter, and 0.7 (p less than 0.002) at 3 mg. per liter. In Experiment 2, the significant effect was found only at the 3 mg. per liter dose, with those mice having 2.3 metastases per mouse as compared with 5.5 in the controls (p less than 0.0001). We conclude that full anticoagulation in the range of 2.5 to 3 times normal is required for a maximal antimetastatic effect."} {"id": "PMID:1273749", "title": "Shunting, release, and distribution of nine and fifteen micron spheres in myocardium.", "content": "The shunting, release, and transmural distribution of 9 and 15 mu radioactive microspheres were compared in isolated hearts and intact hearts with and without adenosine triphosphate (ATP) vasodilation. ATP vasodilation caused increase shunting of 9 mu spheres but not 15 mu spheres (p less than 0.05). The transmural distribution of 9 and 15 mu spheres in left ventricle and septum were significantly different (p less than 0.01) and the difference was characteristic for the isolated heart and the nonvasodilated intact heart. There was no difference in distribution across the right ventricle. There appear to be significant differences in regional shunting as well as distribution in the intact heart. We found no systematic correction for comparing flows measured with 9 and 15 mu spheres.", "contents": "Shunting, release, and distribution of nine and fifteen micron spheres in myocardium. The shunting, release, and transmural distribution of 9 and 15 mu radioactive microspheres were compared in isolated hearts and intact hearts with and without adenosine triphosphate (ATP) vasodilation. ATP vasodilation caused increase shunting of 9 mu spheres but not 15 mu spheres (p less than 0.05). The transmural distribution of 9 and 15 mu spheres in left ventricle and septum were significantly different (p less than 0.01) and the difference was characteristic for the isolated heart and the nonvasodilated intact heart. There was no difference in distribution across the right ventricle. There appear to be significant differences in regional shunting as well as distribution in the intact heart. We found no systematic correction for comparing flows measured with 9 and 15 mu spheres."} {"id": "PMID:1273750", "title": "The response of diastolic myocardial tissue pressure and regional coronary blood flow to increased preload from blood, colloid, crystalloid.", "content": "An increase in the left ventricular end-diastolic pressure (LVEDP), resulting from the intravenous administration of blood, a colloid solution, or a crystalloid solution, was accompanied by an increase in both the inner:outer left ventricular wall flow ratio and the diastolic myocardial tissue pressure gradient. With a normal left ventricular end-diastolic pressure, the normal inner:outer flow ratio was just above unity and the minimum diastolic myocardial tissue pressure in the subepicardium was twice as high as in the subendocardium. When the left ventricular end-diastolic pressure was raised, the subepicardial tissue pressure rose earlier and to a higher degree than the subendocardial; thus a gradient which encourages subendocardial flow was increased. This paper correlates the changes in diastolic myocardial tissue pressure and in inner:outer flow ratios which occurred when eight dogs were transfused with blood, seven with colloid, and seven with lactated Ringer's solution. Regional diastolic myocardial tissue pressure was measured by the flow-cessation technique and regional flow by radioactive microspheres. The gradient in diastolic myocardial tissue pressure, which is a major contributory factor to adequate subendocardial perfusion under normal conditions, is of even greater importance when LVEDP is raised.", "contents": "The response of diastolic myocardial tissue pressure and regional coronary blood flow to increased preload from blood, colloid, crystalloid. An increase in the left ventricular end-diastolic pressure (LVEDP), resulting from the intravenous administration of blood, a colloid solution, or a crystalloid solution, was accompanied by an increase in both the inner:outer left ventricular wall flow ratio and the diastolic myocardial tissue pressure gradient. With a normal left ventricular end-diastolic pressure, the normal inner:outer flow ratio was just above unity and the minimum diastolic myocardial tissue pressure in the subepicardium was twice as high as in the subendocardium. When the left ventricular end-diastolic pressure was raised, the subepicardial tissue pressure rose earlier and to a higher degree than the subendocardial; thus a gradient which encourages subendocardial flow was increased. This paper correlates the changes in diastolic myocardial tissue pressure and in inner:outer flow ratios which occurred when eight dogs were transfused with blood, seven with colloid, and seven with lactated Ringer's solution. Regional diastolic myocardial tissue pressure was measured by the flow-cessation technique and regional flow by radioactive microspheres. The gradient in diastolic myocardial tissue pressure, which is a major contributory factor to adequate subendocardial perfusion under normal conditions, is of even greater importance when LVEDP is raised."} {"id": "PMID:1273751", "title": "Plasma levels of secretin in man and dogs: validation of a secretin radioimmunoassay.", "content": "We have developed and validated a secretin radioimmunoassay that is sufficiently sensitvie to measure circulating levels of secretin in the plasma of man and dogs. At a final dilution of 1:50,000, the antibody bound 30 percent to 40 percent of radioiodinated (125 I) 6-tyrosyl synthetic secretin. Pure natural porcine secretin was used as a reference standard and a linear dose-response curve was generated with 10 to 1,000 pg. of the polypeptide. Little or no cross-reactivity was found when graded doses of other gastrointestinal polypeptides were assayed in the radioimmunoassay and immunoreactive secretin (IRS) in volumes of serum up to 300 mul could be measured accurately.", "contents": "Plasma levels of secretin in man and dogs: validation of a secretin radioimmunoassay. We have developed and validated a secretin radioimmunoassay that is sufficiently sensitvie to measure circulating levels of secretin in the plasma of man and dogs. At a final dilution of 1:50,000, the antibody bound 30 percent to 40 percent of radioiodinated (125 I) 6-tyrosyl synthetic secretin. Pure natural porcine secretin was used as a reference standard and a linear dose-response curve was generated with 10 to 1,000 pg. of the polypeptide. Little or no cross-reactivity was found when graded doses of other gastrointestinal polypeptides were assayed in the radioimmunoassay and immunoreactive secretin (IRS) in volumes of serum up to 300 mul could be measured accurately."} {"id": "PMID:1273752", "title": "Alterations in high-energy phosphates in hemorrhagic shock as related to tissue and organ function.", "content": "Hemorrhagic shock was produced in conscious rats by cannulating the subclavian arteries and bleeding the animals to a mean arterial pressure of 40 mm. Hg, which was maintained for one hour (early shock) or 2 hours (late shock). Analysis of diaphragm (working muscle) showed that there was a significant decrease in adenosine triphosphate (ATP), adenosine diphosphate (ADP), and creatine phosphate levels beginning with early shock, whereas in soleus muscle (resting muscle) these changes were not observed until late shock. Decreases in adenine nucleotides of diaphragm were less than in working organs such as liver and kidney in early shock. This suggests that the extent of decrease in adenine nucleotides during shock may be related to the metabolic activity of the organ.", "contents": "Alterations in high-energy phosphates in hemorrhagic shock as related to tissue and organ function. Hemorrhagic shock was produced in conscious rats by cannulating the subclavian arteries and bleeding the animals to a mean arterial pressure of 40 mm. Hg, which was maintained for one hour (early shock) or 2 hours (late shock). Analysis of diaphragm (working muscle) showed that there was a significant decrease in adenosine triphosphate (ATP), adenosine diphosphate (ADP), and creatine phosphate levels beginning with early shock, whereas in soleus muscle (resting muscle) these changes were not observed until late shock. Decreases in adenine nucleotides of diaphragm were less than in working organs such as liver and kidney in early shock. This suggests that the extent of decrease in adenine nucleotides during shock may be related to the metabolic activity of the organ."} {"id": "PMID:1273753", "title": "Splenic abscess.", "content": "A review of autopsy files and clinical case reports demonstrates two categories of splenic abscess. First, the abscesses discovered at postmortem usually are multiple, small manifestations of widespread, lethal infection in immunologically crippled hosts. A clinical diagnosis seldom is made. Second, the splenic abscesses encountered by the clinician are usually solitary, large, and challenge his diagnostic skills. Recognition is of vital importance, for therapy can be highly successful. Left untreated, the mortality rate is very high. The features, clinical management, and pathogenesis of splenic abscesses are discussed.", "contents": "Splenic abscess. A review of autopsy files and clinical case reports demonstrates two categories of splenic abscess. First, the abscesses discovered at postmortem usually are multiple, small manifestations of widespread, lethal infection in immunologically crippled hosts. A clinical diagnosis seldom is made. Second, the splenic abscesses encountered by the clinician are usually solitary, large, and challenge his diagnostic skills. Recognition is of vital importance, for therapy can be highly successful. Left untreated, the mortality rate is very high. The features, clinical management, and pathogenesis of splenic abscesses are discussed."} {"id": "PMID:1273754", "title": "Evaluation of a prototype therapeutic system for prolonged, continuous topical delivery of homosulfanilamide in the management of Pseudomonas burn wound sepsis.", "content": "The ability of homosulfanilimide (HS) delivered from two different dressing vehicles to limit bacterial proliferation was evaluated in burned animals deliberately infected with virulent Pseudomonas organisms. Treatment consisted of once daily topical application of one of two vehicles: (1) an experimental prototype system that utilized micronized HS in a hydrophobic, bioerodible, polymeric matrix, impregnated on a fabric backing; or (2) a commercially available dressing that contained the same mass of drug in a hydrophilic cream base impregnated on the same backing. Wounds on control animals were covered with fabric backing with or without the bioerodible matrix. The experimental system was designed to maintain a finite local concentration of HS on the burn wound for at least 24 hours. It is known that the cream base presents a rapidly decreasing concentration of drug to the burn surface. HS delivered from the experimental system produced a significant reduction in deaths compared with the HS delivered from the cream base. In addition, the new method of delivering HS provided better control of local and systemic infection, and better wound hydration and also promoted earlier eschar separation. The experimental system was at least as convenient to apply as the cream and had an advantage with respect to inspection of the wound, since it could be removed and reapplied easily.", "contents": "Evaluation of a prototype therapeutic system for prolonged, continuous topical delivery of homosulfanilamide in the management of Pseudomonas burn wound sepsis. The ability of homosulfanilimide (HS) delivered from two different dressing vehicles to limit bacterial proliferation was evaluated in burned animals deliberately infected with virulent Pseudomonas organisms. Treatment consisted of once daily topical application of one of two vehicles: (1) an experimental prototype system that utilized micronized HS in a hydrophobic, bioerodible, polymeric matrix, impregnated on a fabric backing; or (2) a commercially available dressing that contained the same mass of drug in a hydrophilic cream base impregnated on the same backing. Wounds on control animals were covered with fabric backing with or without the bioerodible matrix. The experimental system was designed to maintain a finite local concentration of HS on the burn wound for at least 24 hours. It is known that the cream base presents a rapidly decreasing concentration of drug to the burn surface. HS delivered from the experimental system produced a significant reduction in deaths compared with the HS delivered from the cream base. In addition, the new method of delivering HS provided better control of local and systemic infection, and better wound hydration and also promoted earlier eschar separation. The experimental system was at least as convenient to apply as the cream and had an advantage with respect to inspection of the wound, since it could be removed and reapplied easily."} {"id": "PMID:1273755", "title": "Monitoring of intramuscular pressure.", "content": "Increased pressure within an osteofascial compartment may produce a compartmental syndrome, one of the principal causes of local circulatory compromise in traumatized extremities. In certain instances, monitoring of intracompartmental pressure may be a valuable adjunct in the clinical evaluation of patients at risk for this syndrome.", "contents": "Monitoring of intramuscular pressure. Increased pressure within an osteofascial compartment may produce a compartmental syndrome, one of the principal causes of local circulatory compromise in traumatized extremities. In certain instances, monitoring of intracompartmental pressure may be a valuable adjunct in the clinical evaluation of patients at risk for this syndrome."} {"id": "PMID:1273756", "title": "Abdominal aortic aneurysm and renal hamartoma in an infant with tuberous sclerosis.", "content": "A case is presented of an infant with tuberous sclerosis admitted with status epilepticus. When the seizures were controlled, it was found that the child was hypertensive. A large renal tumor and an abdominal aortic aneurysm was found during the hypertensive evaluation. She underwent abdominal aortic aneurysm resection and radical nephrectomy, and vascular continuity was re-established sucessfully with a Dacron prosthesis. The technique is illustrated. The reconstruction is patent one year following reconstruction. The etiology of the aneurysm is discussed.", "contents": "Abdominal aortic aneurysm and renal hamartoma in an infant with tuberous sclerosis. A case is presented of an infant with tuberous sclerosis admitted with status epilepticus. When the seizures were controlled, it was found that the child was hypertensive. A large renal tumor and an abdominal aortic aneurysm was found during the hypertensive evaluation. She underwent abdominal aortic aneurysm resection and radical nephrectomy, and vascular continuity was re-established sucessfully with a Dacron prosthesis. The technique is illustrated. The reconstruction is patent one year following reconstruction. The etiology of the aneurysm is discussed."} {"id": "PMID:1273757", "title": "Malrotation of the bowel in infants and children: a 15 year review.", "content": "One hundred and fifty-nine patients with malrotation treated in the Children's Hospital Medical Center between 1951 and 1967 are presented and analyzed with regard to the factors contributing to the success or failure of their management. There were 28 deaths, the majority of which occurred in patients who were less than one month old, had multiple congenital anomalies, or had volvulus of the small bowel with gangrene and perforation. Some of the points we have found most helpful in making the diagnosis are reviewed and the disease as it presents in older children is considered briefly.", "contents": "Malrotation of the bowel in infants and children: a 15 year review. One hundred and fifty-nine patients with malrotation treated in the Children's Hospital Medical Center between 1951 and 1967 are presented and analyzed with regard to the factors contributing to the success or failure of their management. There were 28 deaths, the majority of which occurred in patients who were less than one month old, had multiple congenital anomalies, or had volvulus of the small bowel with gangrene and perforation. Some of the points we have found most helpful in making the diagnosis are reviewed and the disease as it presents in older children is considered briefly."} {"id": "PMID:1273760", "title": "Multifactor evaluations of surgical trainees and teaching services.", "content": "Surgical education has been exposed to increasing challenges as students have moved from the highly structured environment of a university hospital into a variety of clinical settings within the community. Presented with a general surgical service that uses ten relatively autonomous teaching services in seven hospitals, we have developed a computer-based evaluation system designed to provide quality control and a feed-back loop for trainee, teacher, and service. Trainees were rated by comparing them to their peers, with the chief resident as a reference standard. Profiles of each teaching service also were developed and compared one to the other. The results of both studies over a one year period are presented.", "contents": "Multifactor evaluations of surgical trainees and teaching services. Surgical education has been exposed to increasing challenges as students have moved from the highly structured environment of a university hospital into a variety of clinical settings within the community. Presented with a general surgical service that uses ten relatively autonomous teaching services in seven hospitals, we have developed a computer-based evaluation system designed to provide quality control and a feed-back loop for trainee, teacher, and service. Trainees were rated by comparing them to their peers, with the chief resident as a reference standard. Profiles of each teaching service also were developed and compared one to the other. The results of both studies over a one year period are presented."} {"id": "PMID:1273761", "title": "Quality assurance: the cost of utilization review and the educational value of medical audit in a university hospital.", "content": "The components of mandated quality assurance, that is, utilization review (UR) and medical audit, have been analyzed to determine their cost-effectiveness and educational value in a university hospital. At Ths in 1975 were $205,272--$6.71 per admission or $0.69 per patient day. The average costs per admission and per patient day in teaching hospitals in the New York area in 1975 were $10.42 and $0.93, respectively. It is anticipated that these costs will increase markedly in 1976 because of admission review. Since 1972 approximately 9,500 hospital charts have been reviewed annually to identify an average of six patients per year who required the intervention of the UR committee because of unnecessarily prolonged length of stay. The cost of identifying each patient was $33, 212. In the university hospital, the active participation of the graduate (house) staff in patient care renders the requirements for certification/recertification of the need for hospital services or admission review superfluous. From September, 1973, through December, 1975, 15 studies of evaluation of medical care (medical audit) have been completed at an average cost of $4,788 per audit. In ten audits the principal criticism was inadequate documentation of data in the hospital record. Nine audits were critical of excessive use of laboratory services and deviations of practice were identified in seven audits. Medical audit has failed to achieve its objective to identify the educational needs of the hospital staff. It is suggested that a more satisfactory and less costly form of medical audit should be devised. Clinical studies, published in scientific journals, should be considered in the context of medical audit.", "contents": "Quality assurance: the cost of utilization review and the educational value of medical audit in a university hospital. The components of mandated quality assurance, that is, utilization review (UR) and medical audit, have been analyzed to determine their cost-effectiveness and educational value in a university hospital. At Ths in 1975 were $205,272--$6.71 per admission or $0.69 per patient day. The average costs per admission and per patient day in teaching hospitals in the New York area in 1975 were $10.42 and $0.93, respectively. It is anticipated that these costs will increase markedly in 1976 because of admission review. Since 1972 approximately 9,500 hospital charts have been reviewed annually to identify an average of six patients per year who required the intervention of the UR committee because of unnecessarily prolonged length of stay. The cost of identifying each patient was $33, 212. In the university hospital, the active participation of the graduate (house) staff in patient care renders the requirements for certification/recertification of the need for hospital services or admission review superfluous. From September, 1973, through December, 1975, 15 studies of evaluation of medical care (medical audit) have been completed at an average cost of $4,788 per audit. In ten audits the principal criticism was inadequate documentation of data in the hospital record. Nine audits were critical of excessive use of laboratory services and deviations of practice were identified in seven audits. Medical audit has failed to achieve its objective to identify the educational needs of the hospital staff. It is suggested that a more satisfactory and less costly form of medical audit should be devised. Clinical studies, published in scientific journals, should be considered in the context of medical audit."} {"id": "PMID:1273762", "title": "The role of prostaglandin E in the hemodynamic response to aortic clamping and declamping.", "content": "The infrarenal aorta was occluded for one hour in 11 control dogs and in eight dogs in which biosynthesis of prostaglandin E (PGE) was inhibited by administration of indomethacin (2.5 mg. per kilogram). The mean arterial pressure (MAP) in the indomethacin group was significantly (p less than 0.001) higher than in the control group at the end of 60 minutes of aortic occlusion (187 +/- 3 vs. 137 +/- 4 mm. Hg, mean +/- S.E.M.) and remained higher (p less than 0.001) after declamping. However, the decline in MAP at the time of aortic declamping was essentially the same for both groups. Total peripheral resistance (TPR) was higher in the indomethacin group than in the control group at the end of one hour of occlusion (159 +/- 13 vs. 124 +/- 12%, p less than 0.001) and remainded higher throughout the period following occlusion. The plasma concentration of PGE in the control group increased significantly (p less than 0.05) above control (630 +/- 110 to 1,299 +/- 261 pg. per milliliter) during the 60 minute period of occlusion with further increases to 1,447 +/- 389 and 1,523 +/- 256 pg. per milliliter (p less than 0.001) at 10 and 60 seconds after declamping, respectively. In the indomethacin group, PGE remained essentially unchanged throughout the clamping and declamping period and therefore was significantly (p less than 0.05) lower than in the control group. A similar pattern was observed in the tissue levels of PGE. This study suggests that PGE is released during and after infrarenal aortic occlusion and may be responsible for maintaining reduced TPR and MAP. However, hypotension after declamping is not affected by inhibition of PGE biosynthesis.", "contents": "The role of prostaglandin E in the hemodynamic response to aortic clamping and declamping. The infrarenal aorta was occluded for one hour in 11 control dogs and in eight dogs in which biosynthesis of prostaglandin E (PGE) was inhibited by administration of indomethacin (2.5 mg. per kilogram). The mean arterial pressure (MAP) in the indomethacin group was significantly (p less than 0.001) higher than in the control group at the end of 60 minutes of aortic occlusion (187 +/- 3 vs. 137 +/- 4 mm. Hg, mean +/- S.E.M.) and remained higher (p less than 0.001) after declamping. However, the decline in MAP at the time of aortic declamping was essentially the same for both groups. Total peripheral resistance (TPR) was higher in the indomethacin group than in the control group at the end of one hour of occlusion (159 +/- 13 vs. 124 +/- 12%, p less than 0.001) and remainded higher throughout the period following occlusion. The plasma concentration of PGE in the control group increased significantly (p less than 0.05) above control (630 +/- 110 to 1,299 +/- 261 pg. per milliliter) during the 60 minute period of occlusion with further increases to 1,447 +/- 389 and 1,523 +/- 256 pg. per milliliter (p less than 0.001) at 10 and 60 seconds after declamping, respectively. In the indomethacin group, PGE remained essentially unchanged throughout the clamping and declamping period and therefore was significantly (p less than 0.05) lower than in the control group. A similar pattern was observed in the tissue levels of PGE. This study suggests that PGE is released during and after infrarenal aortic occlusion and may be responsible for maintaining reduced TPR and MAP. However, hypotension after declamping is not affected by inhibition of PGE biosynthesis."} {"id": "PMID:1273763", "title": "Melanoma of the trunk: the results of surgical excision and anatomic guidelines for predicting nodal metastasis.", "content": "From 1958 through 1969, inclusive, 418 patients with melanoma of the trunk were treated at the M. D. Anderson Hospital and Tumor Institute. Of these, 128 patients (31%) had Stage I disease and were treated by excision with observation of regional nodes in all except five patients. Retrospectively these Stage I patients were analyzed regarding (1) survival, (2) sites and timing of treatment failures, (3) the relation of the primary site to eventual nodal metastasis, and (4) the variables of sex, size, and location on the trunk, which also were correlated with disease control. The results show: (1) actuarial survival rate of 65.7% and 55.7% at 5 and 10 years, respectively; (2) positive regional lymph nodes (RLN) evolved in 34 patients (28%), systemic metastases in 18 patients (15%), local recurrence (LR) in four patients, LR plus RLN in one patient, and intransit metastases in three patients as the first evidence of failure. Over 90% of LR and positive RLN developed within 24 months. Many intransit recurrences and systemic metastases occurred later and account for much of the biologic variability attributed to melanomas: (3) the anatomy of the lymphatics of the trunk as described by Sappey is an excellent guide to the site of first nodal metastasis, (4) a midline or near-midline primary site correlated with regional failure (p less than 0.05). More men failed regionally than did women (p less than 0.05). In retrospective calculation, 184 regional node dissections would have been required for probable salvage of 13 patients (10%) if surgical treatment for subclinical disease had been used routinely.", "contents": "Melanoma of the trunk: the results of surgical excision and anatomic guidelines for predicting nodal metastasis. From 1958 through 1969, inclusive, 418 patients with melanoma of the trunk were treated at the M. D. Anderson Hospital and Tumor Institute. Of these, 128 patients (31%) had Stage I disease and were treated by excision with observation of regional nodes in all except five patients. Retrospectively these Stage I patients were analyzed regarding (1) survival, (2) sites and timing of treatment failures, (3) the relation of the primary site to eventual nodal metastasis, and (4) the variables of sex, size, and location on the trunk, which also were correlated with disease control. The results show: (1) actuarial survival rate of 65.7% and 55.7% at 5 and 10 years, respectively; (2) positive regional lymph nodes (RLN) evolved in 34 patients (28%), systemic metastases in 18 patients (15%), local recurrence (LR) in four patients, LR plus RLN in one patient, and intransit metastases in three patients as the first evidence of failure. Over 90% of LR and positive RLN developed within 24 months. Many intransit recurrences and systemic metastases occurred later and account for much of the biologic variability attributed to melanomas: (3) the anatomy of the lymphatics of the trunk as described by Sappey is an excellent guide to the site of first nodal metastasis, (4) a midline or near-midline primary site correlated with regional failure (p less than 0.05). More men failed regionally than did women (p less than 0.05). In retrospective calculation, 184 regional node dissections would have been required for probable salvage of 13 patients (10%) if surgical treatment for subclinical disease had been used routinely."} {"id": "PMID:1273764", "title": "The effects of pulseless perfusion on the distribution of renal cortical blood flow and on renin release.", "content": "The effects of pulseless perfusion on the distribution of renal blood flow and on release of renin were studied in anesthetized dogs. The distribution of renal blood flow to four cortical layers was determined with the radioactive microsphere technique during pulsatile control conditions and after one and 2 hours of pulseless perfusion, without significant changes in mean arterial pressure and mean total renal blood flow. Simultaneously, renal vein blood samples were analyzed for renin (radioimmunoassay technique). During pulseless perfusion there was a consistent and progressive redistribution of blood flow toward deeper cortical layers with the outer cortical layer falling from 36.9 to 25.3% p less than 0.001) and the juxtamedullary cortex increasing from 14.5 to 25.4% (p less than 0.001) after 2 hours. In addition, there was a progressive increase in renal venous concentration of renin, which was 20.91 +/- 6.6 ng. per millimeter per hour after 2 hours of pulseless flow compared to 5.06 +/- 1.16 ng. per millimeter per hour during control conditions (p less than 0.05). These changes in cortical blood flow and in release of renin were not observed in sham-operated controls. The results indicate that pulseless flow alone produced both a significant increase in renal production of renin and a significant redistribution of renal cortical blood flow, due to the greater vasoconstriction in the outer cortex when compared to the juxtamedullary cortex.", "contents": "The effects of pulseless perfusion on the distribution of renal cortical blood flow and on renin release. The effects of pulseless perfusion on the distribution of renal blood flow and on release of renin were studied in anesthetized dogs. The distribution of renal blood flow to four cortical layers was determined with the radioactive microsphere technique during pulsatile control conditions and after one and 2 hours of pulseless perfusion, without significant changes in mean arterial pressure and mean total renal blood flow. Simultaneously, renal vein blood samples were analyzed for renin (radioimmunoassay technique). During pulseless perfusion there was a consistent and progressive redistribution of blood flow toward deeper cortical layers with the outer cortical layer falling from 36.9 to 25.3% p less than 0.001) and the juxtamedullary cortex increasing from 14.5 to 25.4% (p less than 0.001) after 2 hours. In addition, there was a progressive increase in renal venous concentration of renin, which was 20.91 +/- 6.6 ng. per millimeter per hour after 2 hours of pulseless flow compared to 5.06 +/- 1.16 ng. per millimeter per hour during control conditions (p less than 0.05). These changes in cortical blood flow and in release of renin were not observed in sham-operated controls. The results indicate that pulseless flow alone produced both a significant increase in renal production of renin and a significant redistribution of renal cortical blood flow, due to the greater vasoconstriction in the outer cortex when compared to the juxtamedullary cortex."} {"id": "PMID:1273765", "title": "Myocardial utilization of hypertonic glucose during hemorrhagic shock.", "content": "Awake pigs were rapidly bled 40% of total blood volume to induce hemorrhagic shock. Immediately after the induction of shock, all pigs received a single intravenous injection of radioactive-labeled glucose-U-14C. Simultaneously with glucose-U-14C injection, ten pigs received single central intravenous injections of unlabeled 50% glucose, four pigs received equiosmolar 25% mannitol, six did not receive either 50% glucose or mannitol, and two received 50% glucose plus insulin. Mean arterial pressure with 50% glucose was 89.9 mm. Hg at 15 minutes of shock and significantly higher than without 50% glucose, 48.3 mm. Hg or after mannitol, 46.7 mm. Hg (P = 0.05). Mean cardiac output at 10 minutes of shock with 50% glucose was 2.24 L. per minute and significantly higher than with mannitol, 1.34 L. per minute, or without 50% glucose, 0.94 L. per minute (P = 0.05.). Evidence for increased anaerobic myocardial utilization of the administered unlabeled 50% glucose was shown by a 12% greater production of unlabeled lactate in the venous coronary sinus blood from unlabeled 50% glucose in contrast to those not given 50% glucose at 10 minutes after shock (P = 0.05). Also, 50% glucose significantly increased mean arterial pressure, cardiac output, and survival over both control groups.", "contents": "Myocardial utilization of hypertonic glucose during hemorrhagic shock. Awake pigs were rapidly bled 40% of total blood volume to induce hemorrhagic shock. Immediately after the induction of shock, all pigs received a single intravenous injection of radioactive-labeled glucose-U-14C. Simultaneously with glucose-U-14C injection, ten pigs received single central intravenous injections of unlabeled 50% glucose, four pigs received equiosmolar 25% mannitol, six did not receive either 50% glucose or mannitol, and two received 50% glucose plus insulin. Mean arterial pressure with 50% glucose was 89.9 mm. Hg at 15 minutes of shock and significantly higher than without 50% glucose, 48.3 mm. Hg or after mannitol, 46.7 mm. Hg (P = 0.05). Mean cardiac output at 10 minutes of shock with 50% glucose was 2.24 L. per minute and significantly higher than with mannitol, 1.34 L. per minute, or without 50% glucose, 0.94 L. per minute (P = 0.05.). Evidence for increased anaerobic myocardial utilization of the administered unlabeled 50% glucose was shown by a 12% greater production of unlabeled lactate in the venous coronary sinus blood from unlabeled 50% glucose in contrast to those not given 50% glucose at 10 minutes after shock (P = 0.05). Also, 50% glucose significantly increased mean arterial pressure, cardiac output, and survival over both control groups."} {"id": "PMID:1273766", "title": "The maintenance of gastric mucosal barrier during the early erosive gastritis component of stress ulceration.", "content": "The spectrum of gastric stress ulceration includes early erosive gastritis, which develops within 48 hours of injury, as well as a late ulcerative component. Previous clinical studies with young healthy volunteers as controls have implicated increased back diffusion of hydrogen ions in the pathogenesis of stress ulceration. The present study compares the gastric mucosal integrity of injured patients to an age-matched control population of patients who had undergone elective intra-abdominal operations. These control patients suffered operative injury similar to that of the injured patients and yet, unlike injured patients, they did not develop clinically overt stress ulceration. The patients were studied during the first 2 days following injury and/or operation. No differences were found in the gastric mucosal permeability to hydrogen ions, as measured by back diffusion of hydrogen ions (H+BD) and by absorption of lithium (delta(Li/PSP), between the injured patients and their age-matched controls, despite the subsequent development of clinically overt stress ulceration in 25% of the injured patients. Likewise, there were no differences between the traumatized patients who developed stress ulceration and either their age-matched controls or the remainder of the traumatized patients. These date suggest that increased back diffusion of hydrogen ions cannot be implicated in the erosive gastritis which is the early component of stress ulceration.", "contents": "The maintenance of gastric mucosal barrier during the early erosive gastritis component of stress ulceration. The spectrum of gastric stress ulceration includes early erosive gastritis, which develops within 48 hours of injury, as well as a late ulcerative component. Previous clinical studies with young healthy volunteers as controls have implicated increased back diffusion of hydrogen ions in the pathogenesis of stress ulceration. The present study compares the gastric mucosal integrity of injured patients to an age-matched control population of patients who had undergone elective intra-abdominal operations. These control patients suffered operative injury similar to that of the injured patients and yet, unlike injured patients, they did not develop clinically overt stress ulceration. The patients were studied during the first 2 days following injury and/or operation. No differences were found in the gastric mucosal permeability to hydrogen ions, as measured by back diffusion of hydrogen ions (H+BD) and by absorption of lithium (delta(Li/PSP), between the injured patients and their age-matched controls, despite the subsequent development of clinically overt stress ulceration in 25% of the injured patients. Likewise, there were no differences between the traumatized patients who developed stress ulceration and either their age-matched controls or the remainder of the traumatized patients. These date suggest that increased back diffusion of hydrogen ions cannot be implicated in the erosive gastritis which is the early component of stress ulceration."} {"id": "PMID:1273767", "title": "Coronary and cardiovascular dynamics and oxygen availability during acute normovolemic anemia.", "content": "The hematocrit of 12 dogs was reduced from 43 to 30 and then to 20% by bleeding and simultaneous infusion of lactated Ringer's solution. At each level of anemia, blood volume, heart rate, cardiac output, left and right pressures, left ventricular (LV) work, aortic mean pressure, and systemic vascular resistance were at prebleeding values. Pulmonary arterial saturation decreased from 76 to 67 and 50%. LV coronary venous saturation fell from 46 to 31% at hematocrit 30, with no further reduction at hematocrit 20. Electromagnetically measured left coronary mean flow was 120 and 185% of control at hematocrits 30 and 20. Coronary flow reserve, or the ratio of peak increase in flow after 10 second occlusion to preocclusion flow, was 3.8 at hematocrit 43, 3.0 at 30, and 1.9 at 20. The change in ratio was due to increased resting flow with anemia, whereas peak reactive hyperemia flow did not change with hematocrit. Acute normovolemic anemia is not associated with significant changes in cardiac work. Despite lowered blood viscosity, systemic resistance is maintained by vasoconstriction. Systemic oxygen availability (Cardiac output X arterial O2 content) is decreased, but uptake is maintained by increased O2 extraction. LV O2 consumption is maintained by maximally increasing the already high myocardial O2 extraction and by increasing coronary flow. At half-normal hematocrit, coronary reserve is compromised significantly, indicating cardiac vulnerability at these levels of anemia, especially if coronary occlusive disease or higher work demands on the heart should coexist.", "contents": "Coronary and cardiovascular dynamics and oxygen availability during acute normovolemic anemia. The hematocrit of 12 dogs was reduced from 43 to 30 and then to 20% by bleeding and simultaneous infusion of lactated Ringer's solution. At each level of anemia, blood volume, heart rate, cardiac output, left and right pressures, left ventricular (LV) work, aortic mean pressure, and systemic vascular resistance were at prebleeding values. Pulmonary arterial saturation decreased from 76 to 67 and 50%. LV coronary venous saturation fell from 46 to 31% at hematocrit 30, with no further reduction at hematocrit 20. Electromagnetically measured left coronary mean flow was 120 and 185% of control at hematocrits 30 and 20. Coronary flow reserve, or the ratio of peak increase in flow after 10 second occlusion to preocclusion flow, was 3.8 at hematocrit 43, 3.0 at 30, and 1.9 at 20. The change in ratio was due to increased resting flow with anemia, whereas peak reactive hyperemia flow did not change with hematocrit. Acute normovolemic anemia is not associated with significant changes in cardiac work. Despite lowered blood viscosity, systemic resistance is maintained by vasoconstriction. Systemic oxygen availability (Cardiac output X arterial O2 content) is decreased, but uptake is maintained by increased O2 extraction. LV O2 consumption is maintained by maximally increasing the already high myocardial O2 extraction and by increasing coronary flow. At half-normal hematocrit, coronary reserve is compromised significantly, indicating cardiac vulnerability at these levels of anemia, especially if coronary occlusive disease or higher work demands on the heart should coexist."} {"id": "PMID:1273768", "title": "Temporal factors in the reduction of myocardial infarct volume by methylprednisolone.", "content": "With a canine model of myocardial infarction [ligation of the left anterior descending (LAD) coronary artery] and an intracellular stain for lactic dehydrogenase (LDH) to directly measure size of infarction, the influence of 30 mg. per kilogram of methylprednisolone sodium succinate was evaluted. The intravenous administration of a pharmacologic dose of methylprednisolone one, 2, or 3 hours after the onset of myocardial infarction significantly reduced the ultimate extent of myocardial necrosis, with the greatest reduction seen following the injection of the drug one hour after ligation. The left atrial pressure was significantly decreased by corticosteroid administration, whereas the cardiac index and peripheral vascular tone were improved insignificantly. Inconsistent and/or insignificant effects were observed in the systemic and coronary sinus blood gases and in those indices of myocardial metabolism which were determined. The potential impact of these findings on the clinical applicability of methylprednisolone sodium succinate in acute myocardial ischemia is discussed.", "contents": "Temporal factors in the reduction of myocardial infarct volume by methylprednisolone. With a canine model of myocardial infarction [ligation of the left anterior descending (LAD) coronary artery] and an intracellular stain for lactic dehydrogenase (LDH) to directly measure size of infarction, the influence of 30 mg. per kilogram of methylprednisolone sodium succinate was evaluted. The intravenous administration of a pharmacologic dose of methylprednisolone one, 2, or 3 hours after the onset of myocardial infarction significantly reduced the ultimate extent of myocardial necrosis, with the greatest reduction seen following the injection of the drug one hour after ligation. The left atrial pressure was significantly decreased by corticosteroid administration, whereas the cardiac index and peripheral vascular tone were improved insignificantly. Inconsistent and/or insignificant effects were observed in the systemic and coronary sinus blood gases and in those indices of myocardial metabolism which were determined. The potential impact of these findings on the clinical applicability of methylprednisolone sodium succinate in acute myocardial ischemia is discussed."} {"id": "PMID:1273769", "title": "Total thyroidectomy and parathyroid autotransplantation for radiation-associated thyroid cancer.", "content": "In seventy patients with nodular thyroids and a history of radiation exposure, total thyroidectomy disclosed a 54% incidence of carcinoma; more than half of them had cervial node metastases; four had distant metastases. Fourteen patients required radical neck dissection. The carcinoma was multicentric (both lobes) in 45%. In four patients the carcinoma was found in the lobe contralateral to the one containing the palpable nodule. These findings support the advocates of total thyroidectomy for patients with a nodular thyroid and a history of radiation exposure, provided this operation can be performed with a low incidence of recurrent nerve palsy and hypoparathyroidism.", "contents": "Total thyroidectomy and parathyroid autotransplantation for radiation-associated thyroid cancer. In seventy patients with nodular thyroids and a history of radiation exposure, total thyroidectomy disclosed a 54% incidence of carcinoma; more than half of them had cervial node metastases; four had distant metastases. Fourteen patients required radical neck dissection. The carcinoma was multicentric (both lobes) in 45%. In four patients the carcinoma was found in the lobe contralateral to the one containing the palpable nodule. These findings support the advocates of total thyroidectomy for patients with a nodular thyroid and a history of radiation exposure, provided this operation can be performed with a low incidence of recurrent nerve palsy and hypoparathyroidism."} {"id": "PMID:1273770", "title": "Acute gastric mucosal ulcerogenesis is dependent on the concentration of bile salt.", "content": "Studies on animals implicating reflux of bile salts in formation of \"stress ulcer\" often are suspect because of the inordinately high intragastric concentrations of bile salts used to induce experimental acute gastric mucosal damage. We studied reflux of bile salt in 11 patients after operation. Nine refluxed bile salts in a mean intragastric concentration of 1.87 +/- 0.24 mM. (range, 0.34 to 4.88 mM.). In the present study, therefore, the ulcerogenic potential of physiologic concentrations of bile salts was evaluated. With use of vascularized, chambered canine gastric mucosa, groups of animals were studied during three consecutive periods. Group A = topical acid test alone (ATS) during periods 1, 2, and 3; Group B = (1) ATS, (2) ATS, (3) ATS + vasopressin (VP = 0.1 U per Kg.-min. via the splenic artery); Group C = (1) ATS, (2) ATS + topical 1 mM. sodium taurocholate (TC), (3) ATS + 1 TC + VP; Group D = (1) ATS, (2) ATS + 2 TC, (3) ATS + 2 TC + VP; Group E = (1) ATS (2) ATS + 5 TC, (3) ATS + 5 TC + VP. Parameters evaluated were (1) net fluxes H+, Na+; (2) electrical potential difference (PD); (3) clearance of aminopyrine, a measure of mucosal blood flow (MBF); and (4) formation of lesions, graded zero to six by an independent observer who used photographs. In nonischemic mucosa, bile salts produced no ulcers, a significant concentration-dependent increase in H+ \"back diffusion\" and fall in PD, and a noncentration-dependent increase in MBF. In ischemic mucosa, the combination of topical acid, topical bile salts, and mucosal ischemia was acutely ulcerogenic. The severity of mucosal injury was dependent on the concentration of bile salt (y = 0.108 + 1.53x, r = 0.90, p less than 0.01). These data indicate that acute mucosal damage occurs in the presence of physiologic concentrations of bile salt, i.e., those routinely found in the gastric contents of postoperative patients.", "contents": "Acute gastric mucosal ulcerogenesis is dependent on the concentration of bile salt. Studies on animals implicating reflux of bile salts in formation of \"stress ulcer\" often are suspect because of the inordinately high intragastric concentrations of bile salts used to induce experimental acute gastric mucosal damage. We studied reflux of bile salt in 11 patients after operation. Nine refluxed bile salts in a mean intragastric concentration of 1.87 +/- 0.24 mM. (range, 0.34 to 4.88 mM.). In the present study, therefore, the ulcerogenic potential of physiologic concentrations of bile salts was evaluated. With use of vascularized, chambered canine gastric mucosa, groups of animals were studied during three consecutive periods. Group A = topical acid test alone (ATS) during periods 1, 2, and 3; Group B = (1) ATS, (2) ATS, (3) ATS + vasopressin (VP = 0.1 U per Kg.-min. via the splenic artery); Group C = (1) ATS, (2) ATS + topical 1 mM. sodium taurocholate (TC), (3) ATS + 1 TC + VP; Group D = (1) ATS, (2) ATS + 2 TC, (3) ATS + 2 TC + VP; Group E = (1) ATS (2) ATS + 5 TC, (3) ATS + 5 TC + VP. Parameters evaluated were (1) net fluxes H+, Na+; (2) electrical potential difference (PD); (3) clearance of aminopyrine, a measure of mucosal blood flow (MBF); and (4) formation of lesions, graded zero to six by an independent observer who used photographs. In nonischemic mucosa, bile salts produced no ulcers, a significant concentration-dependent increase in H+ \"back diffusion\" and fall in PD, and a noncentration-dependent increase in MBF. In ischemic mucosa, the combination of topical acid, topical bile salts, and mucosal ischemia was acutely ulcerogenic. The severity of mucosal injury was dependent on the concentration of bile salt (y = 0.108 + 1.53x, r = 0.90, p less than 0.01). These data indicate that acute mucosal damage occurs in the presence of physiologic concentrations of bile salt, i.e., those routinely found in the gastric contents of postoperative patients."} {"id": "PMID:1273814", "title": "[A differential diagnostic abnormality (?) with regard to diarrhoea in calves (author's transl)].", "content": "The following article describes the \"case-history\" of a newborn calf suffering from ordinary calf-diarrhoea. Because the therapy was not successful the animal was examined again. The result was a dichloorvos intoxication caused by a Vaponastrip that was hung up in close contact with the patient.", "contents": "[A differential diagnostic abnormality (?) with regard to diarrhoea in calves (author's transl)]. The following article describes the \"case-history\" of a newborn calf suffering from ordinary calf-diarrhoea. Because the therapy was not successful the animal was examined again. The result was a dichloorvos intoxication caused by a Vaponastrip that was hung up in close contact with the patient."} {"id": "PMID:1273817", "title": "[A study on the bacteriological aspect of fresh beef. I. Effect of the slaughter of cattle (author's transl)].", "content": "In slaughter-houses in the Netherlands the bacteriological contamination of beef-carcases was determined immediately after slaughter. The highest aerobic bacterial count as well as the largest numbers of Enterobacteriaceae were found to be present on the carcases at those sites at which the skin or meat had been cut. It is likely that bacteria are carried from the skin to the meat during cutting. Differences in bacteriological contamination of carcases are attributed to the difference in transmission from the skin. Mechanization of the dressing-line did not have any perceptible effect on the degree of contamination.", "contents": "[A study on the bacteriological aspect of fresh beef. I. Effect of the slaughter of cattle (author's transl)]. In slaughter-houses in the Netherlands the bacteriological contamination of beef-carcases was determined immediately after slaughter. The highest aerobic bacterial count as well as the largest numbers of Enterobacteriaceae were found to be present on the carcases at those sites at which the skin or meat had been cut. It is likely that bacteria are carried from the skin to the meat during cutting. Differences in bacteriological contamination of carcases are attributed to the difference in transmission from the skin. Mechanization of the dressing-line did not have any perceptible effect on the degree of contamination."} {"id": "PMID:1273818", "title": "[A study on the bacteriological aspect of fresh beef. II. Effect of storage of carcases in slaughter-houses (author's transl)].", "content": "Beef carcases were stored in the chilling rooms of seven slaughter-houses for periods varying from ten to thirteen days and bacteriologically examined at regular intervals. At best, the bacteriological state of the carcases continued to be acceptable for nearly two weeks; under adverse conditions, it was acceptable for barely a week. The bacteriological keeping qualities were markedly affected by the temperature and, if to a far less extent, by contamination during slaughter and loss of weight due to evaporation. The importance of these factors as well as that of the method adopted in sampling is stressed.", "contents": "[A study on the bacteriological aspect of fresh beef. II. Effect of storage of carcases in slaughter-houses (author's transl)]. Beef carcases were stored in the chilling rooms of seven slaughter-houses for periods varying from ten to thirteen days and bacteriologically examined at regular intervals. At best, the bacteriological state of the carcases continued to be acceptable for nearly two weeks; under adverse conditions, it was acceptable for barely a week. The bacteriological keeping qualities were markedly affected by the temperature and, if to a far less extent, by contamination during slaughter and loss of weight due to evaporation. The importance of these factors as well as that of the method adopted in sampling is stressed."} {"id": "PMID:1273819", "title": "[Sperm examination of the boar (author's transl)].", "content": "During the last ten years the stock of pigs in the Netherlands has doubled. The number of adult boars on pig farms there has in that time trebled. Sperm examination of boars by the Gezondheidsdienst voor Dieren (Veterinary Health Service) in the Dutch province of North Brabant have increased from 83 boars in 1968 to 2045 boars in 1974. The data of boars examined in 1972, 1973, and 1974 have been used to provide an idea of the effects of breed, age, and season on the reasons for the examination and on the quality of the sperm. The group of boars offered for an informatory examination prior to being used has increased relatively strongly in number.", "contents": "[Sperm examination of the boar (author's transl)]. During the last ten years the stock of pigs in the Netherlands has doubled. The number of adult boars on pig farms there has in that time trebled. Sperm examination of boars by the Gezondheidsdienst voor Dieren (Veterinary Health Service) in the Dutch province of North Brabant have increased from 83 boars in 1968 to 2045 boars in 1974. The data of boars examined in 1972, 1973, and 1974 have been used to provide an idea of the effects of breed, age, and season on the reasons for the examination and on the quality of the sperm. The group of boars offered for an informatory examination prior to being used has increased relatively strongly in number."} {"id": "PMID:1273822", "title": "[The most suitable time for mating of the bitch (author's transl)].", "content": "The literature on the oestrous cycle in the bitch is briefly reviewed. 283 bitches were studied in order to develop a procedure by which to determine the time of ovulation, i.e., the optimum time for mating or insemination. Examination of vaginal smears, clinical observations of the bitch and sugar tests of the vaginal discharge showed that the sugar test is the most satisfactory method in dog-breeding and, particularly, that it is simple to use. The mean conception rate of the bitches which were inseminated was 71 per cent.", "contents": "[The most suitable time for mating of the bitch (author's transl)]. The literature on the oestrous cycle in the bitch is briefly reviewed. 283 bitches were studied in order to develop a procedure by which to determine the time of ovulation, i.e., the optimum time for mating or insemination. Examination of vaginal smears, clinical observations of the bitch and sugar tests of the vaginal discharge showed that the sugar test is the most satisfactory method in dog-breeding and, particularly, that it is simple to use. The mean conception rate of the bitches which were inseminated was 71 per cent."} {"id": "PMID:1273823", "title": "[Investigation of the incidence of Salmonella in the Faeces, mesenteric lymph glands, and intestinal wall (Peyer's patches) of normal pig carcases (author's transl)].", "content": "The faeces, mesenteric lymph glands, and intestinal wall (Peyer's patches) of two hundred clinically normal pig carcases were examined. Of these, 115 (57.5%) were found to infected with Salmonella in the following combinations: lymph glands only, 6; intestines only, 14; faeces only, 13; lymph glands + intestines, 7; lymph glands + faeces, 11; intestines + faeces, 20; lymph glands + intestines + faeces, 44. The supposition that Salmonella can be detected in the lymphoid tissue of the intestine (Peyer's patches) far more frequently than in the faeces was not confirmed. The presumably still rising number of clinically healthy butcher's pig which are actually infected with Salmonella is pointed out.", "contents": "[Investigation of the incidence of Salmonella in the Faeces, mesenteric lymph glands, and intestinal wall (Peyer's patches) of normal pig carcases (author's transl)]. The faeces, mesenteric lymph glands, and intestinal wall (Peyer's patches) of two hundred clinically normal pig carcases were examined. Of these, 115 (57.5%) were found to infected with Salmonella in the following combinations: lymph glands only, 6; intestines only, 14; faeces only, 13; lymph glands + intestines, 7; lymph glands + faeces, 11; intestines + faeces, 20; lymph glands + intestines + faeces, 44. The supposition that Salmonella can be detected in the lymphoid tissue of the intestine (Peyer's patches) far more frequently than in the faeces was not confirmed. The presumably still rising number of clinically healthy butcher's pig which are actually infected with Salmonella is pointed out."} {"id": "PMID:1273824", "title": "[Rupture of the uterus during gestation (author's transl)].", "content": "The case of rupture of the uterus in a heifer approximately seven weeks before parturition is reported. The history suggested a disorder of the digestive tract. In view of the results of clinical studies in conjunction with examination of the blood, rupture of the uterus was suspected. This was verified by post-mortem findings.", "contents": "[Rupture of the uterus during gestation (author's transl)]. The case of rupture of the uterus in a heifer approximately seven weeks before parturition is reported. The history suggested a disorder of the digestive tract. In view of the results of clinical studies in conjunction with examination of the blood, rupture of the uterus was suspected. This was verified by post-mortem findings."} {"id": "PMID:1273827", "title": "No indication of postnatal selection at the HL-A loci.", "content": "When the HL--A allele frequency and the distribution of 2, 3 and 4 different antigens, respectively, in children and old people were compared no differences could be observed between the two groups. The data thus disprove a simple model by which HL--A heterozygosity should enhance surveillance.", "contents": "No indication of postnatal selection at the HL-A loci. When the HL--A allele frequency and the distribution of 2, 3 and 4 different antigens, respectively, in children and old people were compared no differences could be observed between the two groups. The data thus disprove a simple model by which HL--A heterozygosity should enhance surveillance."} {"id": "PMID:1273829", "title": "Genetic independence between the HL--A system and deficits in the first and sixth components of complement.", "content": "From two families, one with Clr deficiency and the other with C6 deficiency, evidence was obtained suggesting genetic independence between the transmission of a 50% deficit in the functional activity of these two complement components and the inheritance of the HL--A system, the ABO system, and the sex of individuals.", "contents": "Genetic independence between the HL--A system and deficits in the first and sixth components of complement. From two families, one with Clr deficiency and the other with C6 deficiency, evidence was obtained suggesting genetic independence between the transmission of a 50% deficit in the functional activity of these two complement components and the inheritance of the HL--A system, the ABO system, and the sex of individuals."} {"id": "PMID:1273875", "title": "[Gonadal load in the radiotherapy of benign diseases. I. Degenerative joint diseases].", "content": "The gonadal load was measured during radiation therapy of humeroscapular periarthritis, coxarthrosis, diseases of the vertebral column and of the sacro-iliac joint (disease Bechterew) for different irradiation techniques. All measurements have been performed by LiF dosimeters and with an Alderson phantom using 250 kV X-radiation. The gonadal dose with respect to the surface dose was in the range of tenths of one per mill in case of humeroscapular periarthritis and reached values up to about 30 per cent in coxarthrosis and Bechterew disease. Measurements during irradiation of the vertebral column yielded most differing values of the gonadal load depending on gonadal distances from the region exposed.", "contents": "[Gonadal load in the radiotherapy of benign diseases. I. Degenerative joint diseases]. The gonadal load was measured during radiation therapy of humeroscapular periarthritis, coxarthrosis, diseases of the vertebral column and of the sacro-iliac joint (disease Bechterew) for different irradiation techniques. All measurements have been performed by LiF dosimeters and with an Alderson phantom using 250 kV X-radiation. The gonadal dose with respect to the surface dose was in the range of tenths of one per mill in case of humeroscapular periarthritis and reached values up to about 30 per cent in coxarthrosis and Bechterew disease. Measurements during irradiation of the vertebral column yielded most differing values of the gonadal load depending on gonadal distances from the region exposed."} {"id": "PMID:1273876", "title": "[Radiogenic nephritis in relation to splenectomy and irradiation of the spleen bed].", "content": "Five cases are reported where under curative aspects the splenic region was irradiated during radiation therapy of lymphogranulomatosis. In the course of this treatment, a radiation load amounting to 3000 up to 4200 R focal dose occurred to the upper pole of the left kidney. A LESION OF THE LEft kidney was diagnosed not earlier than nine or twelve months afterwards in three of the patients. Two patients could be followed up as yet only four or five months. As for verification of the circumscribed radiogenic nephritis, renal scintigraphy proved the best technique to provide information. Short-term check-up examinations are necessary for the purposes of early recognition and efficient therapy of this complication, the prognosis of lymphogranulomatosis being on the whole relatively good.", "contents": "[Radiogenic nephritis in relation to splenectomy and irradiation of the spleen bed]. Five cases are reported where under curative aspects the splenic region was irradiated during radiation therapy of lymphogranulomatosis. In the course of this treatment, a radiation load amounting to 3000 up to 4200 R focal dose occurred to the upper pole of the left kidney. A LESION OF THE LEft kidney was diagnosed not earlier than nine or twelve months afterwards in three of the patients. Two patients could be followed up as yet only four or five months. As for verification of the circumscribed radiogenic nephritis, renal scintigraphy proved the best technique to provide information. Short-term check-up examinations are necessary for the purposes of early recognition and efficient therapy of this complication, the prognosis of lymphogranulomatosis being on the whole relatively good."} {"id": "PMID:1273877", "title": "[Consideration of large in homogeneous regions of the computation of electron dose distributions].", "content": "A simple method, suggested by Laughlin and Pohlit for calculation of dose distribution in electron beams which is considering the nonhomogeneous structure of the body, has been examined with regard to its accuracy within the energy range up to 42 MeV. Thereby, the dose distributions calculated and measured over nonhomogeneous thorax phantoms were compared. The method is based on the dose in homogeneous muscular tissue for a depth of area-weight identical to that in nonhomogeneous tissue with corrections being made according to the law of squared distances. Thus, only the loss of electron energy but not the scattering is considered. Smaller nonhomogeneous zones are completely neglected, larger ones treated as regions of equal density. The present study of the region of the lung and previous papers concerning bones [13] and cavities [11] show that the method, apart from near surface cavities, yields a satisfying exactness of the calculated dose distributions. If larger inhomogeneities - especially of the lung - are regarded, their mean tissue density, their shape, size and location ought to be known as exactly as possible.", "contents": "[Consideration of large in homogeneous regions of the computation of electron dose distributions]. A simple method, suggested by Laughlin and Pohlit for calculation of dose distribution in electron beams which is considering the nonhomogeneous structure of the body, has been examined with regard to its accuracy within the energy range up to 42 MeV. Thereby, the dose distributions calculated and measured over nonhomogeneous thorax phantoms were compared. The method is based on the dose in homogeneous muscular tissue for a depth of area-weight identical to that in nonhomogeneous tissue with corrections being made according to the law of squared distances. Thus, only the loss of electron energy but not the scattering is considered. Smaller nonhomogeneous zones are completely neglected, larger ones treated as regions of equal density. The present study of the region of the lung and previous papers concerning bones [13] and cavities [11] show that the method, apart from near surface cavities, yields a satisfying exactness of the calculated dose distributions. If larger inhomogeneities - especially of the lung - are regarded, their mean tissue density, their shape, size and location ought to be known as exactly as possible."} {"id": "PMID:1273878", "title": "Dose contribution to regional lymph nodes from gynecological remote afterloading cobalt-60 sources.", "content": "Dose contribution to the regional lymph nodes from high dose rate gynecological intracavitary technique was studied. For computer, calculating radiation dosage, rectangular lymphograms were taken. The average dose to point B and obturator nodes was nearly equal, 29-28% of point A dose. The common iliac nodes received the lowest dose, 14% of point A dose on the average. Due to the wide variation in the position of the uterus (deviation and dislocation), the dose at each of the two corresponding points or nodes (right and left side) was never equal. The effect of the uterus deviation and dislocation on the dose distribution was also studied in computer model display. We managed to describe this effect by an exponential curve. Because of the wide variation in the position of the uterus, only the individual dose calculation to the lymph nodes makes it possible to determine the most accurate amount of additional external irradiation.", "contents": "Dose contribution to regional lymph nodes from gynecological remote afterloading cobalt-60 sources. Dose contribution to the regional lymph nodes from high dose rate gynecological intracavitary technique was studied. For computer, calculating radiation dosage, rectangular lymphograms were taken. The average dose to point B and obturator nodes was nearly equal, 29-28% of point A dose. The common iliac nodes received the lowest dose, 14% of point A dose on the average. Due to the wide variation in the position of the uterus (deviation and dislocation), the dose at each of the two corresponding points or nodes (right and left side) was never equal. The effect of the uterus deviation and dislocation on the dose distribution was also studied in computer model display. We managed to describe this effect by an exponential curve. Because of the wide variation in the position of the uterus, only the individual dose calculation to the lymph nodes makes it possible to determine the most accurate amount of additional external irradiation."} {"id": "PMID:1273879", "title": "[Uric acid balance in radiotherapy].", "content": "Administration of uricostatics within the scope of radiotherapeutic treatment is indicated in all cases of manifest primary gout; in cases of latent primary gout, uricostatics should be given especially after administration of high integral doses or in case of large tumors with distinct radiation sensitivity. The decision depends on the renal function, as an increased output of substances to be eliminated by urine may induce an attack of gout in cases of latent gout, or, otherwise, may cause renal lesions followed by acute uric acid nephropathy.", "contents": "[Uric acid balance in radiotherapy]. Administration of uricostatics within the scope of radiotherapeutic treatment is indicated in all cases of manifest primary gout; in cases of latent primary gout, uricostatics should be given especially after administration of high integral doses or in case of large tumors with distinct radiation sensitivity. The decision depends on the renal function, as an increased output of substances to be eliminated by urine may induce an attack of gout in cases of latent gout, or, otherwise, may cause renal lesions followed by acute uric acid nephropathy."} {"id": "PMID:1273880", "title": "A radioprotective effect of calcium chloride in combination with cystamine, mexamine, and hypoxemic hypoxia in mice.", "content": "A mild protective effect of a solution of CaCl2 (3.21 g%) injected in a volume of 0.2 ml i.p. 30 minutes prior to irradiation was demonstrated in experiments with male mice in the strain C 57 B1/10. The pre-irradiation administration of CaCl2 increased the LD50/30 by approximately 60R as compared with control animals, to which an isoosmotic NaCl solution was injected. A more pronounced decrease of the post-irradiation mortality of the animals was reached by combined administration of CaCl2 with chemical protectors- cystamine or mexamine administered in relatively low s.c. doses, as well as by a combination of CaCl2 with the protective action of hypoxemic hypoxia. Under the conditions of combined protection, the administration of CaCl2 increased LD50/30 by approximately 100 to 130R. A higher rate of formation of endogenous spleen hematopoietic colonies was observed in the animals protected by calcium. Possible mechanisms of the radioprotective effect of calcium on the level of the hematopoietic stem cells are discussed.", "contents": "A radioprotective effect of calcium chloride in combination with cystamine, mexamine, and hypoxemic hypoxia in mice. A mild protective effect of a solution of CaCl2 (3.21 g%) injected in a volume of 0.2 ml i.p. 30 minutes prior to irradiation was demonstrated in experiments with male mice in the strain C 57 B1/10. The pre-irradiation administration of CaCl2 increased the LD50/30 by approximately 60R as compared with control animals, to which an isoosmotic NaCl solution was injected. A more pronounced decrease of the post-irradiation mortality of the animals was reached by combined administration of CaCl2 with chemical protectors- cystamine or mexamine administered in relatively low s.c. doses, as well as by a combination of CaCl2 with the protective action of hypoxemic hypoxia. Under the conditions of combined protection, the administration of CaCl2 increased LD50/30 by approximately 100 to 130R. A higher rate of formation of endogenous spleen hematopoietic colonies was observed in the animals protected by calcium. Possible mechanisms of the radioprotective effect of calcium on the level of the hematopoietic stem cells are discussed."} {"id": "PMID:1273881", "title": "[Electron microscopy studies on the pinocytosis activity of Ehrlich ascites tumor cells in monolayer culture].", "content": "During the phase of exponential growth ferritin was added to the culture medium of monolayer cell cultures from the Ehrlich ascites tumor in order to observe the pinocytosis phenomenon in these cells by means of electron microscopy. After a phase of adsorption, the ferritin arrived in vesicles and vacuoles of the cytoplasm - probably by ligature of coat invaginations. Within larger-sized vesicles, which might have been formed by fusion of smaller ones, less electron-dense ferritin-free internal compartments are resulting possibly from interaction with primary lysosomes; this is interpreted as a sign of interior digestive phenomena. Sometimes, this internal compartment was coated with a structure similar to a membrane. In the further course, concentration of the electron-dense zones containing ferritin occurred in the marginal zone of the vacuoles. Some vacuoles comprised two or three of the less electron-dense compartments. Vacuoles containing ferritin were also observed comprising residual membranes. The formation of these transition stages to residual bodies is regarded as an interaction and fusion of heterophagocytic or autophagocytic vacuoles with primary lysosomes.", "contents": "[Electron microscopy studies on the pinocytosis activity of Ehrlich ascites tumor cells in monolayer culture]. During the phase of exponential growth ferritin was added to the culture medium of monolayer cell cultures from the Ehrlich ascites tumor in order to observe the pinocytosis phenomenon in these cells by means of electron microscopy. After a phase of adsorption, the ferritin arrived in vesicles and vacuoles of the cytoplasm - probably by ligature of coat invaginations. Within larger-sized vesicles, which might have been formed by fusion of smaller ones, less electron-dense ferritin-free internal compartments are resulting possibly from interaction with primary lysosomes; this is interpreted as a sign of interior digestive phenomena. Sometimes, this internal compartment was coated with a structure similar to a membrane. In the further course, concentration of the electron-dense zones containing ferritin occurred in the marginal zone of the vacuoles. Some vacuoles comprised two or three of the less electron-dense compartments. Vacuoles containing ferritin were also observed comprising residual membranes. The formation of these transition stages to residual bodies is regarded as an interaction and fusion of heterophagocytic or autophagocytic vacuoles with primary lysosomes."} {"id": "PMID:1273882", "title": "[Animal experiments on the use of ozone in irradiated and non-irradiated tumors. III. Ehrlich-ascite carcinoma cells in vitro].", "content": "Measurements carried in vitro were carried out concerning the effectof ozone either by itself or combined with X-ray therapy (single dose of 2000 R) on the reproductive capacity of Ehrlich-ascites cancer cells. The strongest combination effect is stated when ozone is administered after irradiation. The findings and results of this study are compared with hypotheses and results described in the corresponding literature.", "contents": "[Animal experiments on the use of ozone in irradiated and non-irradiated tumors. III. Ehrlich-ascite carcinoma cells in vitro]. Measurements carried in vitro were carried out concerning the effectof ozone either by itself or combined with X-ray therapy (single dose of 2000 R) on the reproductive capacity of Ehrlich-ascites cancer cells. The strongest combination effect is stated when ozone is administered after irradiation. The findings and results of this study are compared with hypotheses and results described in the corresponding literature."} {"id": "PMID:1273884", "title": "Sterols of scallop. Part II. Structure of unknown sterols by combination gas-liquid chromatography and mass spectrometry.", "content": "Four sterols, isolated from the scallop Pacopecten magellanicus have been identified as 24-nor-5alpha-cholest-22-en-3beta-ol; 24-norcholest-5-en-3beta-ol; 5alpha-cholest-22-en-3beta-ol; and (E) -24-propylidenecholest-5-en-3beta-ol. These bring to seventeen the total number of sterols identified in this marine mollusc. A fifth newly detected sterol, closely similar in its mass spectrometric properties is 22-cis and trans-cholesta-5, 22-dien-3beta-ol, was clearly distinguished from these by its shorter retention time by GLC.", "contents": "Sterols of scallop. Part II. Structure of unknown sterols by combination gas-liquid chromatography and mass spectrometry. Four sterols, isolated from the scallop Pacopecten magellanicus have been identified as 24-nor-5alpha-cholest-22-en-3beta-ol; 24-norcholest-5-en-3beta-ol; 5alpha-cholest-22-en-3beta-ol; and (E) -24-propylidenecholest-5-en-3beta-ol. These bring to seventeen the total number of sterols identified in this marine mollusc. A fifth newly detected sterol, closely similar in its mass spectrometric properties is 22-cis and trans-cholesta-5, 22-dien-3beta-ol, was clearly distinguished from these by its shorter retention time by GLC."} {"id": "PMID:1273885", "title": "Oxidation of 17-methylene steroids by thallium (III) and mercury (II) acetates.", "content": "The reaction of 17-methylene steroids with T1 (OAc)3 in hot AcOH results in the formation of a mixture of allylic compounds. Oxymercuration in t-BuOH followed by reductive demercuration affords 17-methylene-16beta -hydroxyderivatives as the major products.", "contents": "Oxidation of 17-methylene steroids by thallium (III) and mercury (II) acetates. The reaction of 17-methylene steroids with T1 (OAc)3 in hot AcOH results in the formation of a mixture of allylic compounds. Oxymercuration in t-BuOH followed by reductive demercuration affords 17-methylene-16beta -hydroxyderivatives as the major products."} {"id": "PMID:1273886", "title": "Total synthesis of diazasteroids (1).", "content": "Contrary to previous reports, the condensation product of 8-aminoquinoline (1) and 2-carbethoxycyclopentanone (2) undergoes ring closure with polyphosphoric acid to give the 1, 11-diazasteroid 5. Catalytic hydrogenation reduced the A ring and the double bond to produce 6. 8-Aminotetrahydroquinoline (7) and 3-carbethoxy-2-piperidone condense to a tricyclic intermediate (11), which could not be cyclized to a steroid, however.", "contents": "Total synthesis of diazasteroids (1). Contrary to previous reports, the condensation product of 8-aminoquinoline (1) and 2-carbethoxycyclopentanone (2) undergoes ring closure with polyphosphoric acid to give the 1, 11-diazasteroid 5. Catalytic hydrogenation reduced the A ring and the double bond to produce 6. 8-Aminotetrahydroquinoline (7) and 3-carbethoxy-2-piperidone condense to a tricyclic intermediate (11), which could not be cyclized to a steroid, however."} {"id": "PMID:1273887", "title": "Pregnanetriolone, a normal steroid metabolite: its excretion by normal, Cushing's syndrome and congenital adrenal hyperplasia subjects.", "content": "Synthesis of 3H-pregnanetriolone permitted the estimation of pregnanetriolone in urine with a sensitivity in excess of most previous claims. A good correlation (r = +0.97) was obtained between the values from gas liquid chromatography and those of a double isotope derivative method. In contrast to previous reports, these methods indicated that pregnanetriolone is excreted by normal adults. Urinary pregnanetriolone levels were 18-59 mug/24hr for normal subjects, 35-290mug/24hr in Cushing's syndrome and 250-7000 mug/24hr with congenital adrenal hyperplasia. It is concluded that pregnanetriolone is a normal steroid metabolite and its occurrence in Cushing's syndrome does not necessary indicate an abnormal steroid biosynthetic pathway.", "contents": "Pregnanetriolone, a normal steroid metabolite: its excretion by normal, Cushing's syndrome and congenital adrenal hyperplasia subjects. Synthesis of 3H-pregnanetriolone permitted the estimation of pregnanetriolone in urine with a sensitivity in excess of most previous claims. A good correlation (r = +0.97) was obtained between the values from gas liquid chromatography and those of a double isotope derivative method. In contrast to previous reports, these methods indicated that pregnanetriolone is excreted by normal adults. Urinary pregnanetriolone levels were 18-59 mug/24hr for normal subjects, 35-290mug/24hr in Cushing's syndrome and 250-7000 mug/24hr with congenital adrenal hyperplasia. It is concluded that pregnanetriolone is a normal steroid metabolite and its occurrence in Cushing's syndrome does not necessary indicate an abnormal steroid biosynthetic pathway."} {"id": "PMID:1273888", "title": "Syntheses and ultraviolet absorption of aza-steroids.", "content": "A series of aza-steroids was synthesized containing chromophoric groups, such as a, beta-unsaturated ketones and doubly unsaturated conjugated and monoconjugated heteroannular dienones with the heteroatom in the D ring at the 20 and 17a positions. The effect of an appositely placed electronegative center in these molecules upon their ultraviolet absorptions was studied. In order to obtain a basis for the observed spectral changes, the corresponding carbocyclic compounds were also synthesized. The maximum absorptions of the aza-steroids were hypsochromically shifted relative to the carbocyclic compounds in all cases (n=8). The displacement caused by the electronegative center on absorption maximum of the chromophores is, however, highly dependent on its location within the molecules.", "contents": "Syntheses and ultraviolet absorption of aza-steroids. A series of aza-steroids was synthesized containing chromophoric groups, such as a, beta-unsaturated ketones and doubly unsaturated conjugated and monoconjugated heteroannular dienones with the heteroatom in the D ring at the 20 and 17a positions. The effect of an appositely placed electronegative center in these molecules upon their ultraviolet absorptions was studied. In order to obtain a basis for the observed spectral changes, the corresponding carbocyclic compounds were also synthesized. The maximum absorptions of the aza-steroids were hypsochromically shifted relative to the carbocyclic compounds in all cases (n=8). The displacement caused by the electronegative center on absorption maximum of the chromophores is, however, highly dependent on its location within the molecules."} {"id": "PMID:1273889", "title": "Cholesteryl sulfate and sterol sulfatase in the human reproductive tract.", "content": "Cholesteryl sulfate is a component of human seminal plasma (avg. 445 mug%) and spermatozoa (15 mug/10 (9) cells) and represents more than 85% of the sterol sulfate fraction. This conjugate is avidly bound by spermatozoa when compared to other steroids or steroid sulfates. Autoradiographic localization of CS associated with the spermatozoa revealed a greater accumulation of the radioactivity in the acrosomal region in many, but not all, of those cells examined. Semen is not a site of metabolism of the sterol sulfate but the enzyme, sterol sulfatase, is present in the human female reproductive tract. This cleavage enzyme was detected in Graafian follicles and the activity in the endometrium was ten-fold that found in the Fallopian tube. These findings lead to the proposal that cholesteryl sulfate, an amphipathic molecule ideally suited for interaction with membrane components and implicated in erythrocyte membrane stabilization, may be involved in membrane modifications of the spermatozoa during the process of fertilization.", "contents": "Cholesteryl sulfate and sterol sulfatase in the human reproductive tract. Cholesteryl sulfate is a component of human seminal plasma (avg. 445 mug%) and spermatozoa (15 mug/10 (9) cells) and represents more than 85% of the sterol sulfate fraction. This conjugate is avidly bound by spermatozoa when compared to other steroids or steroid sulfates. Autoradiographic localization of CS associated with the spermatozoa revealed a greater accumulation of the radioactivity in the acrosomal region in many, but not all, of those cells examined. Semen is not a site of metabolism of the sterol sulfate but the enzyme, sterol sulfatase, is present in the human female reproductive tract. This cleavage enzyme was detected in Graafian follicles and the activity in the endometrium was ten-fold that found in the Fallopian tube. These findings lead to the proposal that cholesteryl sulfate, an amphipathic molecule ideally suited for interaction with membrane components and implicated in erythrocyte membrane stabilization, may be involved in membrane modifications of the spermatozoa during the process of fertilization."} {"id": "PMID:1273890", "title": "The molecular structure of 3-methoxy-9 (10 leads to 19) abeo- 1,3, 5, (10)-estratrien-17-one.", "content": "The crystal and molecular structure of 3-methoxy-9(10 leads to 19)abeo-1,3,5(10)-estratrien-17-one has been determined by X-ray analysis in order to ascertain the configuration at C(9). The seven-membered B-ring has a chair conformation and this causes the molecule to bow towards the alpha-face rather than towards the beta-face as in estradiol.", "contents": "The molecular structure of 3-methoxy-9 (10 leads to 19) abeo- 1,3, 5, (10)-estratrien-17-one. The crystal and molecular structure of 3-methoxy-9(10 leads to 19)abeo-1,3,5(10)-estratrien-17-one has been determined by X-ray analysis in order to ascertain the configuration at C(9). The seven-membered B-ring has a chair conformation and this causes the molecule to bow towards the alpha-face rather than towards the beta-face as in estradiol."} {"id": "PMID:1273891", "title": "Synthesis of 18-substituted steroids Part II (1). Improvements in the preparation of 18-hydroxyprogesterone.", "content": "18-Hydroxyprogesterone is conveniently prepared from 3beta-acetoxypregn-5-en-20beta-ol by a modified route. 3beta-Acetoxy-18-iodopregn-5-en-20-one, obtained by the hypoiodite-photolysis procedure and oxidation, is treated with methanolic silver acetate to give the 18, 20-epoxy-20-methoxy derivative, which crystallises directly without need for chromatography. Hydrolysis of the 3-acetate, and a modified Oppenauer oxidation, gave 18-hydroxy-progesterone in 24% over-all yield.", "contents": "Synthesis of 18-substituted steroids Part II (1). Improvements in the preparation of 18-hydroxyprogesterone. 18-Hydroxyprogesterone is conveniently prepared from 3beta-acetoxypregn-5-en-20beta-ol by a modified route. 3beta-Acetoxy-18-iodopregn-5-en-20-one, obtained by the hypoiodite-photolysis procedure and oxidation, is treated with methanolic silver acetate to give the 18, 20-epoxy-20-methoxy derivative, which crystallises directly without need for chromatography. Hydrolysis of the 3-acetate, and a modified Oppenauer oxidation, gave 18-hydroxy-progesterone in 24% over-all yield."} {"id": "PMID:1273892", "title": "Proton magnetic resonance spectra of tetracyclic triterpene alcohols under the influence of a lanthanide shift reagent.", "content": "The proton magnetic resonance spectra were measured for four series of tetracyclic triterpen-3beta-ols, i.e. 5alpha-lanostane, 5alpha-euphane, 5alpha-tirucallane, and 5alpha-dammarane series, in the presence of a molar equivalent of tris (dipivalomethanato) europium, a lanthanide shift reagent. The spectral pattern measured in the presence of the shift reagent was found useful for distinguishing each series and also for characterizing each skeletal isomer of tetracyclic triterpene alcohols.", "contents": "Proton magnetic resonance spectra of tetracyclic triterpene alcohols under the influence of a lanthanide shift reagent. The proton magnetic resonance spectra were measured for four series of tetracyclic triterpen-3beta-ols, i.e. 5alpha-lanostane, 5alpha-euphane, 5alpha-tirucallane, and 5alpha-dammarane series, in the presence of a molar equivalent of tris (dipivalomethanato) europium, a lanthanide shift reagent. The spectral pattern measured in the presence of the shift reagent was found useful for distinguishing each series and also for characterizing each skeletal isomer of tetracyclic triterpene alcohols."} {"id": "PMID:1273893", "title": "16-sulfates of estriol in body fluids of human pregnancy at term.", "content": "A method was developed for the assay of estriol-16-sulfate (E3-16S) and estriol-3, 16-disulfate (E3-3,16-diS) in maternal serum, cord serum and amniotic fluid at delivery in human pregnancy. Tritiated E3-16S and E3-3,16-diS are added to the fluid being analyzed. The conjugates are separated and purified by sequential chromatography on alumina, Celite and Sephadex LH-20. Each conjugate is hydrolyzed with Glusulase and the released estriol is quantified by radioimmmunoassay. E3-3,16-diS was found in each fluid, most concentrated in the cord serum. Small amounts of E3-16S were found in some amniotic fluids, and this conjugate was virtually absent from the sera. These new estriol conjugates comprise less than 1 percent of total, estriol, apparently too low to be of diagnostic value in human pregnancy.", "contents": "16-sulfates of estriol in body fluids of human pregnancy at term. A method was developed for the assay of estriol-16-sulfate (E3-16S) and estriol-3, 16-disulfate (E3-3,16-diS) in maternal serum, cord serum and amniotic fluid at delivery in human pregnancy. Tritiated E3-16S and E3-3,16-diS are added to the fluid being analyzed. The conjugates are separated and purified by sequential chromatography on alumina, Celite and Sephadex LH-20. Each conjugate is hydrolyzed with Glusulase and the released estriol is quantified by radioimmmunoassay. E3-3,16-diS was found in each fluid, most concentrated in the cord serum. Small amounts of E3-16S were found in some amniotic fluids, and this conjugate was virtually absent from the sera. These new estriol conjugates comprise less than 1 percent of total, estriol, apparently too low to be of diagnostic value in human pregnancy."} {"id": "PMID:1273894", "title": "Endogenous concentration of progesterone and 2 slpha -pregnane-3,20-dione in rat decidula tissue.", "content": "The endogenous concentration of progesterone (P) and 5 alpha-pregnane-3,20-dione (5AP) were determined in the dedicual tissue of mature rats by radiommunoassay. On the 4th day of pseudopregnancy the uterine concentration was 281 +/- 28 ng/g for P and 266 +/- 41 ng/g for 5AP. Horns were traumatized on the 4th day of pseudopregnancy. On the 4th day following trauma the endometrial concentration of P was 100 +/- 7 ng/g and for 5AP was 104 +/- 10 ng/g. Plasma concentrations were 35.5 +/- 4.1 ng/g. For P and 16.1 +/- 4.9 ng/ml for 5AP. When one horn was removed and the contralateral horn was traumatized, there was direct correlation between the endogenous concentrations of P and 5AP in the previously removed utraumatized horn and the amount of decidual tissue in the contralateral horn 4 days following trauma (r2 = .8949). These experiments indicate the endometrial response to progesterone is a complex process determined in part by local metabolsm and the ability of the uterus to concentrate P.", "contents": "Endogenous concentration of progesterone and 2 slpha -pregnane-3,20-dione in rat decidula tissue. The endogenous concentration of progesterone (P) and 5 alpha-pregnane-3,20-dione (5AP) were determined in the dedicual tissue of mature rats by radiommunoassay. On the 4th day of pseudopregnancy the uterine concentration was 281 +/- 28 ng/g for P and 266 +/- 41 ng/g for 5AP. Horns were traumatized on the 4th day of pseudopregnancy. On the 4th day following trauma the endometrial concentration of P was 100 +/- 7 ng/g and for 5AP was 104 +/- 10 ng/g. Plasma concentrations were 35.5 +/- 4.1 ng/g. For P and 16.1 +/- 4.9 ng/ml for 5AP. When one horn was removed and the contralateral horn was traumatized, there was direct correlation between the endogenous concentrations of P and 5AP in the previously removed utraumatized horn and the amount of decidual tissue in the contralateral horn 4 days following trauma (r2 = .8949). These experiments indicate the endometrial response to progesterone is a complex process determined in part by local metabolsm and the ability of the uterus to concentrate P."} {"id": "PMID:1273896", "title": "A rapid specific radioimmunoassay for unconjugated estriol in plasma.", "content": "A rapid, non-chromatographic radioimmunossaay for unconjugated estriol in pregnancy plasma has been developed which utilizes a commonly available antiestrogen antisera. Estradiol-17beta and estrone demonstrate 135% relative cross-reactivity with our antiserum, as compared with 100% for estriol. Specificity is achieved by purification of estriol with solvent partitioning using benzene: petroleum ether (1:1). The results obtained using this method are similar to a radioimmunoassay utilizing a highly specific, but commercially unavailable, antiestriol antiserum. The method is precise, with coefficients of variation ranging from 3.0 to 8.2%.", "contents": "A rapid specific radioimmunoassay for unconjugated estriol in plasma. A rapid, non-chromatographic radioimmunossaay for unconjugated estriol in pregnancy plasma has been developed which utilizes a commonly available antiestrogen antisera. Estradiol-17beta and estrone demonstrate 135% relative cross-reactivity with our antiserum, as compared with 100% for estriol. Specificity is achieved by purification of estriol with solvent partitioning using benzene: petroleum ether (1:1). The results obtained using this method are similar to a radioimmunoassay utilizing a highly specific, but commercially unavailable, antiestriol antiserum. The method is precise, with coefficients of variation ranging from 3.0 to 8.2%."} {"id": "PMID:1273897", "title": "Synthesis of estrogen methyl ethers by extractive alkylation.", "content": "A rapid method for the quantitative preparation of a number of estrogen methyl ethers is described. Estrogen in aqueous base is extracted as an ion pair with the tetrahexylammonium oin into methylene chloride where irreversible alkylation (extractive alkylation) by methyl iodide occurs. Gas chromatography (GC) - mass spectrometry (MS) provided the basis for identification of the methylated products. Estrone (1) and estradiol were easily 3-0-methylated whereas estriol gave a dimethylated product. Further experiments suggested that dimethylation of 2-hydroxyestrone in reasonable yield was possible.", "contents": "Synthesis of estrogen methyl ethers by extractive alkylation. A rapid method for the quantitative preparation of a number of estrogen methyl ethers is described. Estrogen in aqueous base is extracted as an ion pair with the tetrahexylammonium oin into methylene chloride where irreversible alkylation (extractive alkylation) by methyl iodide occurs. Gas chromatography (GC) - mass spectrometry (MS) provided the basis for identification of the methylated products. Estrone (1) and estradiol were easily 3-0-methylated whereas estriol gave a dimethylated product. Further experiments suggested that dimethylation of 2-hydroxyestrone in reasonable yield was possible."} {"id": "PMID:1273898", "title": "Decomposition of 11-deoxycorticosterone and corticosterone in soda-lime glass.", "content": "When methanolic solutions of tritiated 11-deoxycorticosterone or corticosterone (0.1 to 300 ng) were evaporated to dryness with a stream of nitrogen in soda-lime test tubes only 8-24% of the radioactivity was recovered as the parent steroid. Evaporation in borosilicate test tubes led to a recovery of 90% or more. With ethyl acetate as solvent no decomposition occured in soda-lime test tubes.", "contents": "Decomposition of 11-deoxycorticosterone and corticosterone in soda-lime glass. When methanolic solutions of tritiated 11-deoxycorticosterone or corticosterone (0.1 to 300 ng) were evaporated to dryness with a stream of nitrogen in soda-lime test tubes only 8-24% of the radioactivity was recovered as the parent steroid. Evaporation in borosilicate test tubes led to a recovery of 90% or more. With ethyl acetate as solvent no decomposition occured in soda-lime test tubes."} {"id": "PMID:1273899", "title": "Radioimmunoassays for free and conjugated trienbolone and for trienbolone acetate in bovine tissue and plasma samples.", "content": "A specific, sensitive, precise and accurate radioimmunoassay has been developed for the quantitation of the synthetic anabolic steroid trienbolone acetate (TBA) and its major metabolites, free and conjugated trienbolone (TBOH) in bovine tissues and plasma. With the extraction procedure described unspecific interference with the antigen-antibody reaction could be ruled out. The assay can significantly detect amounts of more than 40 pg TBOH and 70 pg TBA. 0.1 - 2.0 g tissue and 0.1 - 1 ml plasma are sufficient for 1 determination. Residues (range 0.1 -2.0 ng/g) were still present in calves 69 days after implantation of \"Revalor\" (20 mg estradiol-17beta and 140 mg TBA) with the highest concentrations found in liver and TBA could only be quantitated in fat.", "contents": "Radioimmunoassays for free and conjugated trienbolone and for trienbolone acetate in bovine tissue and plasma samples. A specific, sensitive, precise and accurate radioimmunoassay has been developed for the quantitation of the synthetic anabolic steroid trienbolone acetate (TBA) and its major metabolites, free and conjugated trienbolone (TBOH) in bovine tissues and plasma. With the extraction procedure described unspecific interference with the antigen-antibody reaction could be ruled out. The assay can significantly detect amounts of more than 40 pg TBOH and 70 pg TBA. 0.1 - 2.0 g tissue and 0.1 - 1 ml plasma are sufficient for 1 determination. Residues (range 0.1 -2.0 ng/g) were still present in calves 69 days after implantation of \"Revalor\" (20 mg estradiol-17beta and 140 mg TBA) with the highest concentrations found in liver and TBA could only be quantitated in fat."} {"id": "PMID:1273900", "title": "Derivatives of the insect moulting hormone for affinity chromatography, and their biological activities.", "content": "Several derivatives of the arthropod moulting hormone have been synthesized which were coupled to AH Sepharose 4B yielding about 2 mumole ligand per g wet gel. As an indication of the suitability of the ligands for biological work the puff inducing capacity of their methyl esters was tested. The methyl ester of inokosterone-C-26-carboxylic acid possesses the highest biological activity; lower activities were obtained with the esters of ecdysterone-C-6-CM-oxime and ecdysterone hemisuccinates. Therefore, inokosterone-C-26-carbocylic acid should be a useful ligand for affinity chromatography of ecdysone recptors from insect tissues.", "contents": "Derivatives of the insect moulting hormone for affinity chromatography, and their biological activities. Several derivatives of the arthropod moulting hormone have been synthesized which were coupled to AH Sepharose 4B yielding about 2 mumole ligand per g wet gel. As an indication of the suitability of the ligands for biological work the puff inducing capacity of their methyl esters was tested. The methyl ester of inokosterone-C-26-carboxylic acid possesses the highest biological activity; lower activities were obtained with the esters of ecdysterone-C-6-CM-oxime and ecdysterone hemisuccinates. Therefore, inokosterone-C-26-carbocylic acid should be a useful ligand for affinity chromatography of ecdysone recptors from insect tissues."} {"id": "PMID:1273901", "title": "Effect of anticoagulants and inhibitors of platelet aggregation on thrombotic occlusion of endarterectomized cat carotid arteries.", "content": "Cat carotid arteries measuring 1.8 to 2 mm in diameter were endarterectomized under the operating microscope over a 1-cm segment and the arteriotomy was closed with a 9-0 monofilament nylon suture. Vessels exhibiting significant narrowing of the lumen due to faulty closure of the arteriotomy were excluded from the study. The vessels were divided into six groups according to the method of treatment of the animals: control, aspirin, Coumadin, Coumadin plus aspirin, heparin for less than four hours, and heparin for four to eight hours. All vessels in the untreated group subjected to simple arteriotomy and closure remained patent. Only heparin demonstrated an apparent beneficial effect after endarterectomy with 100% of the vessels treated more than four hours and 30% of those treated less than four hours remaining patent. This is contrasted to a 0% patency in other endarterectomized vessels.", "contents": "Effect of anticoagulants and inhibitors of platelet aggregation on thrombotic occlusion of endarterectomized cat carotid arteries. Cat carotid arteries measuring 1.8 to 2 mm in diameter were endarterectomized under the operating microscope over a 1-cm segment and the arteriotomy was closed with a 9-0 monofilament nylon suture. Vessels exhibiting significant narrowing of the lumen due to faulty closure of the arteriotomy were excluded from the study. The vessels were divided into six groups according to the method of treatment of the animals: control, aspirin, Coumadin, Coumadin plus aspirin, heparin for less than four hours, and heparin for four to eight hours. All vessels in the untreated group subjected to simple arteriotomy and closure remained patent. Only heparin demonstrated an apparent beneficial effect after endarterectomy with 100% of the vessels treated more than four hours and 30% of those treated less than four hours remaining patent. This is contrasted to a 0% patency in other endarterectomized vessels."} {"id": "PMID:1273902", "title": "How often are brain infarcts caused by hypotensive episodes?", "content": "Of 135 patients who were resuscitated after cardiac arrest and who died from one day to several weeks later with morphological signs of systemic cerebral anoxia, there were seven patients (5.2%) with brain infarcts probably caused by hypotensive episodes during or after the resuscitation. There was almost no increase in the frequency of recent brain infarcts with an increasing degree of cerebral atherosclerosis (P greater than 0.90). In contrast, the distribution of ten old brain infarcts in the same material showed a significant correlation to the degree of cerebral atherosclerosis (P less than 0.05). The findings suggest that the combination of cerebral atherosclerotic stenoses and hypotensive is not a major cause of brain infarcts in elderly people. It is suggested that the risk of precipitating brain infarcts by lowering BP in hypertensive patients is not much greater in atherosclerotic than in nonatherosclerotic subjects.", "contents": "How often are brain infarcts caused by hypotensive episodes? Of 135 patients who were resuscitated after cardiac arrest and who died from one day to several weeks later with morphological signs of systemic cerebral anoxia, there were seven patients (5.2%) with brain infarcts probably caused by hypotensive episodes during or after the resuscitation. There was almost no increase in the frequency of recent brain infarcts with an increasing degree of cerebral atherosclerosis (P greater than 0.90). In contrast, the distribution of ten old brain infarcts in the same material showed a significant correlation to the degree of cerebral atherosclerosis (P less than 0.05). The findings suggest that the combination of cerebral atherosclerotic stenoses and hypotensive is not a major cause of brain infarcts in elderly people. It is suggested that the risk of precipitating brain infarcts by lowering BP in hypertensive patients is not much greater in atherosclerotic than in nonatherosclerotic subjects."} {"id": "PMID:1273903", "title": "Distribution of cardiac output in dogs during intravenous infusion of betahistine.", "content": "Cardiac output (CO), arterial blood pressure (ABP), heart rate (HR), blood gases and blood flow (BF) to the brain, heart, kidney and skeletal muscles and other cephalic tissues in five dogs were studied before and at 30 minutes of betahistine infusion (0.12 to 0.2 mg per minute per kilogram). The particle distribution method using radioactive labeled 141Ce (15 mu) and 85Sr (15 mu) microspheres was utilized to quantitate and assess BF and CO. In the five dogs, the increase in CO averaged 20.8%, ABP remained constant, and HR increased in all but one exception where it decreased slightly concomitant with a decrease in Paco2. Brain BF increased (+ 29.6%) in the dogs whose Paco2 reamined constant. The BF increased to the heart (25.4%) and skeletal muslce (80%), while BF to the kidney and other tissues did not change. The change in HR appears to account for the change in CO. The dilating effect of betahistine on blood vessels, in the skeletal muscle, brain and heart could reduce peripheral resistance and decreace ABP. Thus, the increase in HR may be mediated through baroreceptor mechanisms rather than by a direct effect of betahistine. In addition, a decrease in Paco2, is more effective for decreasing cerebral BF than betahistine is for increasing blood flow.", "contents": "Distribution of cardiac output in dogs during intravenous infusion of betahistine. Cardiac output (CO), arterial blood pressure (ABP), heart rate (HR), blood gases and blood flow (BF) to the brain, heart, kidney and skeletal muscles and other cephalic tissues in five dogs were studied before and at 30 minutes of betahistine infusion (0.12 to 0.2 mg per minute per kilogram). The particle distribution method using radioactive labeled 141Ce (15 mu) and 85Sr (15 mu) microspheres was utilized to quantitate and assess BF and CO. In the five dogs, the increase in CO averaged 20.8%, ABP remained constant, and HR increased in all but one exception where it decreased slightly concomitant with a decrease in Paco2. Brain BF increased (+ 29.6%) in the dogs whose Paco2 reamined constant. The BF increased to the heart (25.4%) and skeletal muslce (80%), while BF to the kidney and other tissues did not change. The change in HR appears to account for the change in CO. The dilating effect of betahistine on blood vessels, in the skeletal muscle, brain and heart could reduce peripheral resistance and decreace ABP. Thus, the increase in HR may be mediated through baroreceptor mechanisms rather than by a direct effect of betahistine. In addition, a decrease in Paco2, is more effective for decreasing cerebral BF than betahistine is for increasing blood flow."} {"id": "PMID:1273904", "title": "The \"richness\" of sympathetic innervation. A comparison of cerebral and extracerebral blood vessels.", "content": "The number of adrengeric nerves was quantified, on both cerebral and femoral blood vessels. No difference was found between the two vascular beds. The data failed to establish a \"richer\" innervation of cerebral vessels. This is in agreement with my previous, extensive, subjective, and unpublished impression. Consequently, the suggestion of others, which ascribes certain features of cerebrovascular behavior to an unusually rich vascular innervation, remained unproved.", "contents": "The \"richness\" of sympathetic innervation. A comparison of cerebral and extracerebral blood vessels. The number of adrengeric nerves was quantified, on both cerebral and femoral blood vessels. No difference was found between the two vascular beds. The data failed to establish a \"richer\" innervation of cerebral vessels. This is in agreement with my previous, extensive, subjective, and unpublished impression. Consequently, the suggestion of others, which ascribes certain features of cerebrovascular behavior to an unusually rich vascular innervation, remained unproved."} {"id": "PMID:1273905", "title": "Clinical implications of the Doppler cerebrovascular examination: a correlation with angiography.", "content": "A directional Doppler ultrasound cerebrovascular examination was compared with angiographical findings of 152 internal carotid arteries. The Doppler examination was abnormal in 36 of 38 (95%) arteries with occlusion or stenosis greater than 75%. Of 63 arteries with lesser degrees of stenosis, the Doppler examination identified only four. There were no false-positive Doppler examinations. If the decision to perform angiography had been predicated exclusively on the presence of abnormal Doppler findings, 61 of 101 (60%) carotid lesions of potential clinical significance would have been overlooked. While the Doppler ultrasound cerebrovascular examinations is the most useful noninvasive technique available for the evaluation of certain specific categories of patients with cerebrovascular disease, the technique is based on hemodynamic alterations of pressure and flow, and cannot be expected to identify the relatively large number of non-hemodynamically significant carotid lesions that are still clinically significant as sources of emboli. This paper illustrates that in the routine evaluation of patients with symptomatic cerebrovascular disease, the Doppler examination should not play a part in the decision to proceed with angiography.", "contents": "Clinical implications of the Doppler cerebrovascular examination: a correlation with angiography. A directional Doppler ultrasound cerebrovascular examination was compared with angiographical findings of 152 internal carotid arteries. The Doppler examination was abnormal in 36 of 38 (95%) arteries with occlusion or stenosis greater than 75%. Of 63 arteries with lesser degrees of stenosis, the Doppler examination identified only four. There were no false-positive Doppler examinations. If the decision to perform angiography had been predicated exclusively on the presence of abnormal Doppler findings, 61 of 101 (60%) carotid lesions of potential clinical significance would have been overlooked. While the Doppler ultrasound cerebrovascular examinations is the most useful noninvasive technique available for the evaluation of certain specific categories of patients with cerebrovascular disease, the technique is based on hemodynamic alterations of pressure and flow, and cannot be expected to identify the relatively large number of non-hemodynamically significant carotid lesions that are still clinically significant as sources of emboli. This paper illustrates that in the routine evaluation of patients with symptomatic cerebrovascular disease, the Doppler examination should not play a part in the decision to proceed with angiography."} {"id": "PMID:1273907", "title": "Pial arteriolar responses in the mouse brain revisited.", "content": "Arteriolar responses were measured on the cerebral surface of the mouse using an image splitter and TV monitor. The response to locally applied norepinephrine (NOR) was significantly more frequent for vessels greater than 30 mu I.D. than for smaller vessels. However, even the smaller vessels were frequently constricted by NOR in doses of 5 mug per milliliter. Reserpine (5 mg per kilogram) failed to alter the response to NOR at either 24 or 72 hours after reserpinization. At 48 hours the threshold dose of NOR was reduced, but the effect was slight (two-tailed, P = 0.08). Both propranolol (10(-6) M3 and phentolamine (10(-5M) blocked responses to 5 mug per milliliter of NOR, but neither agent altered resting arteriolar diameter. Isoproterenol, tyramine, and histamine had no effect. Serotonin (5HT) constricted the arterioles but did not potentiate the response to NOR. Additive or potentiated effects were not observed with NOR 5HT or histamine in any combination. These data indicate the presence of alpha-adrenergic receptors in murine cerebral surface arterioles, but do not establish a significant tonic effect of norepinephrine. The existence or role of a beta-receptor in these murine cerebral surface arterioles remains an unsettled question.", "contents": "Pial arteriolar responses in the mouse brain revisited. Arteriolar responses were measured on the cerebral surface of the mouse using an image splitter and TV monitor. The response to locally applied norepinephrine (NOR) was significantly more frequent for vessels greater than 30 mu I.D. than for smaller vessels. However, even the smaller vessels were frequently constricted by NOR in doses of 5 mug per milliliter. Reserpine (5 mg per kilogram) failed to alter the response to NOR at either 24 or 72 hours after reserpinization. At 48 hours the threshold dose of NOR was reduced, but the effect was slight (two-tailed, P = 0.08). Both propranolol (10(-6) M3 and phentolamine (10(-5M) blocked responses to 5 mug per milliliter of NOR, but neither agent altered resting arteriolar diameter. Isoproterenol, tyramine, and histamine had no effect. Serotonin (5HT) constricted the arterioles but did not potentiate the response to NOR. Additive or potentiated effects were not observed with NOR 5HT or histamine in any combination. These data indicate the presence of alpha-adrenergic receptors in murine cerebral surface arterioles, but do not establish a significant tonic effect of norepinephrine. The existence or role of a beta-receptor in these murine cerebral surface arterioles remains an unsettled question."} {"id": "PMID:1273910", "title": "The dilemma of family planning in a North Indian State.", "content": "An empirical study of the family planning program and its clients in the rural areas of Allahabad Division of Uttar Pradesh in India was undertaken in 1971-1972. While family planning acceptance in this region is low, interviews with villagers and family planning staff suggest that organizational shortcomings of the program may help to explain the low level of acceptance. The reported level of contact between the program field staff and the village population was unexpectedly low. The paper discusses a number of administrative problems within the family planning organization, especially at the level of the primary health center. It is concluded that in designing family planning programs, efforts should be made to minimize organizational requirements.", "contents": "The dilemma of family planning in a North Indian State. An empirical study of the family planning program and its clients in the rural areas of Allahabad Division of Uttar Pradesh in India was undertaken in 1971-1972. While family planning acceptance in this region is low, interviews with villagers and family planning staff suggest that organizational shortcomings of the program may help to explain the low level of acceptance. The reported level of contact between the program field staff and the village population was unexpectedly low. The paper discusses a number of administrative problems within the family planning organization, especially at the level of the primary health center. It is concluded that in designing family planning programs, efforts should be made to minimize organizational requirements."} {"id": "PMID:1273906", "title": "Neurological outcome of prolonged coma survivors of out-of-hospital cardiac arrest.", "content": "Nine adult survivors of out-of-hospital presumed cardiogenic cardiac arrest, who remained unresponsive for longer than their third hospital day and who eventually were discharged from the acute care hospital, are reported. Their neurological outcome fell into three distinct categories: (a) a persistent vegetative state, (b) able to follow some simple commands but requiring total nursing care, and (c) able to perform most activities of daily living but unemployable because of marked organic deficits.", "contents": "Neurological outcome of prolonged coma survivors of out-of-hospital cardiac arrest. Nine adult survivors of out-of-hospital presumed cardiogenic cardiac arrest, who remained unresponsive for longer than their third hospital day and who eventually were discharged from the acute care hospital, are reported. Their neurological outcome fell into three distinct categories: (a) a persistent vegetative state, (b) able to follow some simple commands but requiring total nursing care, and (c) able to perform most activities of daily living but unemployable because of marked organic deficits."} {"id": "PMID:1273911", "title": "Modernism and contraceptive use in Colombia.", "content": "This analysis addresses the question of whether fertility can be lowered without the prior occurrence of the social and economic changes that have come to be labeled modernization. The data show that there exists in Colombia a relatively high level of motivation to control fertility that, for many women, is not coupled with both knowledge of and access to a method of contraception. For the \"traditional\" woman, the problem may not be lack of motivation so much as lack of access to methods that she is aware of, such as the pill, and lack of knowledge of methods that require few resources of supplies, such as rhythm and withdrawal.", "contents": "Modernism and contraceptive use in Colombia. This analysis addresses the question of whether fertility can be lowered without the prior occurrence of the social and economic changes that have come to be labeled modernization. The data show that there exists in Colombia a relatively high level of motivation to control fertility that, for many women, is not coupled with both knowledge of and access to a method of contraception. For the \"traditional\" woman, the problem may not be lack of motivation so much as lack of access to methods that she is aware of, such as the pill, and lack of knowledge of methods that require few resources of supplies, such as rhythm and withdrawal."} {"id": "PMID:1273908", "title": "Reversibility of the chronic post-stroke state.", "content": "Forty patients with cerebral infarction associated with occlusion of the internal carotid artery (ICA) or the middle cerebral artery (MCA) were treated with hyperbaric oxygenation (HO). EEG analyses were performed regularly in order to assess the course of the cerebral lesion. Patients in an early post-stroke stage (III B) and patients in a chronic post-stroke stage (IV) had the changes in EEG analysis and neurological distributed evenly between these two groups.", "contents": "Reversibility of the chronic post-stroke state. Forty patients with cerebral infarction associated with occlusion of the internal carotid artery (ICA) or the middle cerebral artery (MCA) were treated with hyperbaric oxygenation (HO). EEG analyses were performed regularly in order to assess the course of the cerebral lesion. Patients in an early post-stroke stage (III B) and patients in a chronic post-stroke stage (IV) had the changes in EEG analysis and neurological distributed evenly between these two groups."} {"id": "PMID:1273909", "title": "Diplopia and involuntary eye closure in spontaneous cerebellar hemorrhage.", "content": "Spontaneous cerebellar hemorrhage is of difficult clinical diagnosis. The causes can be varied, but the hemorrhage is most often associated with hypertensive cardiovascular disease. The neurological symptomatology is complex and often misleading. The diagnosis is mainly dependent of familiarity of the eye signs seen in this disease. Among these, the spontaneous unilateral eye closure is presented as an additional striking manifestation. The displacement of the brain stem by the hematoma is frequently associated with a seventh nerve palsy on the side of the hemorrhage. The patient in an effort to obviate the diplopia caused by the gaze dissociations and extraocular motor palsies, has only the option to close the eye on the noninvolved side of the face, and thus the eye remaining open is on the side of the cerebellar hematoma. This paper presents reports of two patients with these symptoms.", "contents": "Diplopia and involuntary eye closure in spontaneous cerebellar hemorrhage. Spontaneous cerebellar hemorrhage is of difficult clinical diagnosis. The causes can be varied, but the hemorrhage is most often associated with hypertensive cardiovascular disease. The neurological symptomatology is complex and often misleading. The diagnosis is mainly dependent of familiarity of the eye signs seen in this disease. Among these, the spontaneous unilateral eye closure is presented as an additional striking manifestation. The displacement of the brain stem by the hematoma is frequently associated with a seventh nerve palsy on the side of the hemorrhage. The patient in an effort to obviate the diplopia caused by the gaze dissociations and extraocular motor palsies, has only the option to close the eye on the noninvolved side of the face, and thus the eye remaining open is on the side of the cerebellar hematoma. This paper presents reports of two patients with these symptoms."} {"id": "PMID:1273913", "title": "The integrity of tubular cell function after preservation in Collins' or Sacks' solution.", "content": "Collins' solution is an excellent medium for kidney preservation by simple cold storage before transplantation. Efforts by Sacks et al. to improve this technique by modifying the composition seemed promising. A comparison between ability of these two media to preserve the tubular cell was attempted. The viability of the tubular cells was evaluated by measuring the 125 I Hippuran uptake in cortex slices taken from kidneys preserved for 24 and 48 hr in the respective solutions. Kidneys exposed to as well as kidneys not exposed to warm ischaemia were used. Collins' solution was found to be superior in protecting the cell function. Nonetheless intracellular oedema during preservation was greater after preservation in this solution as compared with cells preserved in Sacks' solution.", "contents": "The integrity of tubular cell function after preservation in Collins' or Sacks' solution. Collins' solution is an excellent medium for kidney preservation by simple cold storage before transplantation. Efforts by Sacks et al. to improve this technique by modifying the composition seemed promising. A comparison between ability of these two media to preserve the tubular cell was attempted. The viability of the tubular cells was evaluated by measuring the 125 I Hippuran uptake in cortex slices taken from kidneys preserved for 24 and 48 hr in the respective solutions. Kidneys exposed to as well as kidneys not exposed to warm ischaemia were used. Collins' solution was found to be superior in protecting the cell function. Nonetheless intracellular oedema during preservation was greater after preservation in this solution as compared with cells preserved in Sacks' solution."} {"id": "PMID:1273981", "title": "The theory of high-altitide corrections to the U.S. Navy standard decompression tables. The cross corrections.", "content": "The theoretical basis for the Cross high-altitude corrections to the USN Standard Decompression Tables is derived. Providing corrections are made for depth and ascent rate and if no decompression stops are made, a dive at altitude can be transformed to a dive at sea level for which the theoretical tissue responses are mathematically similar to the altitude dive. The transformation fails if decompression stops are required due to the fact that the stop criteria used in the USN Tables do not obey the same rule of transformation. It is shown that the failure of the high-altitude correction is expected to be conservative.", "contents": "The theory of high-altitide corrections to the U.S. Navy standard decompression tables. The cross corrections. The theoretical basis for the Cross high-altitude corrections to the USN Standard Decompression Tables is derived. Providing corrections are made for depth and ascent rate and if no decompression stops are made, a dive at altitude can be transformed to a dive at sea level for which the theoretical tissue responses are mathematically similar to the altitude dive. The transformation fails if decompression stops are required due to the fact that the stop criteria used in the USN Tables do not obey the same rule of transformation. It is shown that the failure of the high-altitude correction is expected to be conservative."} {"id": "PMID:1273982", "title": "Narcotic potency of N2, A, and N2O evaluated by the physical performance of mouse colonies at simulated depths.", "content": "The physical performance of colonies of deer mice was studied in various inert gas environments at pressures up to 31 ATA. The mice were housed in habitats wherein their diurnal running activity and social interactions could be monitored. By transferring the portable habitats and mouse colonies to a high pressure chamber, the effects of elevated inert gas pressures were studied in socially and ecologically intact surroundings. Analysis of wheel-running performance showed that either 1.1 atm nitrous oxide, 7.2 atm argon, or 20.5 atm nitrogen reduced running activity to 50% of its control value. Behavioral observations revealed a deterioration of physical performance and social interaction with increasing inert gas pressures. A comparison was made between ED50 (the dose that will depress a particular response by 50%) values obtained by studying wheel-running activity and those published for single-reflex responses.", "contents": "Narcotic potency of N2, A, and N2O evaluated by the physical performance of mouse colonies at simulated depths. The physical performance of colonies of deer mice was studied in various inert gas environments at pressures up to 31 ATA. The mice were housed in habitats wherein their diurnal running activity and social interactions could be monitored. By transferring the portable habitats and mouse colonies to a high pressure chamber, the effects of elevated inert gas pressures were studied in socially and ecologically intact surroundings. Analysis of wheel-running performance showed that either 1.1 atm nitrous oxide, 7.2 atm argon, or 20.5 atm nitrogen reduced running activity to 50% of its control value. Behavioral observations revealed a deterioration of physical performance and social interaction with increasing inert gas pressures. A comparison was made between ED50 (the dose that will depress a particular response by 50%) values obtained by studying wheel-running activity and those published for single-reflex responses."} {"id": "PMID:1273983", "title": "Coral-algal associations: capacity for producing and sustaining elevated oxygen tensions in situ.", "content": "Net oxygen production during photosynthesis by all plants requires adaptation to intracellular O2 tensions in excess of 0.21 ATA. The symbiotic association of zooxanthellae (algae) in the tissues of many actinozoans and hydrozoans (corals and anemones) suggests such an adaptation in these tissues as well, and raises the question as to degree. Oxygen production by zooxanthellae in a single coral head of Montastrea cavernosum was monitored daily in situ in a closed, recirculating 15-liter system. The net photosynthetic activity repeatedly raised the PO2 to more than 0.5 ATA, indicating that even higher tensions existed in the coral's tissues in order to cause this increase and suggesting that coral tissue may represent another example of an oxygen-adapted tissue.", "contents": "Coral-algal associations: capacity for producing and sustaining elevated oxygen tensions in situ. Net oxygen production during photosynthesis by all plants requires adaptation to intracellular O2 tensions in excess of 0.21 ATA. The symbiotic association of zooxanthellae (algae) in the tissues of many actinozoans and hydrozoans (corals and anemones) suggests such an adaptation in these tissues as well, and raises the question as to degree. Oxygen production by zooxanthellae in a single coral head of Montastrea cavernosum was monitored daily in situ in a closed, recirculating 15-liter system. The net photosynthetic activity repeatedly raised the PO2 to more than 0.5 ATA, indicating that even higher tensions existed in the coral's tissues in order to cause this increase and suggesting that coral tissue may represent another example of an oxygen-adapted tissue."} {"id": "PMID:1273984", "title": "An audiometric survey of Navy divers.", "content": "The pure tone audiograms of a diverse group of U.S. Navy divers were examined across four major variables: (1) number of years of Navy diving experience, (2) previous noise exposure history, (3) previous history of barotrauma, and (4) type of equipment used, i.e. scuba and helmet. The results obtained suggest that these variables had only minimal effects on auditory sensitivity and that when the hearing of these divers was compared to a normal population of nondivers, no significant differences were detected. A comparison of these findings with those in the existing diving literature was then made.", "contents": "An audiometric survey of Navy divers. The pure tone audiograms of a diverse group of U.S. Navy divers were examined across four major variables: (1) number of years of Navy diving experience, (2) previous noise exposure history, (3) previous history of barotrauma, and (4) type of equipment used, i.e. scuba and helmet. The results obtained suggest that these variables had only minimal effects on auditory sensitivity and that when the hearing of these divers was compared to a normal population of nondivers, no significant differences were detected. A comparison of these findings with those in the existing diving literature was then made."} {"id": "PMID:1273985", "title": "Respiratory gas exchange and lung perfusion in man during and after head-out water immersion.", "content": "The respiratory gas exchange for O2, CO2, and CO has been studied in nine healthy male subjects before, during, and after head-out water immersion. Distribution of lung perfusion and ventilation were determined by quantitative double nuclide scintigraphy (131J and 99mTc) and by argon washout, respectively. The well-known decrease of PaO2 and increase of AaDO2 during immersion is accompanied by a decrease of the CO-transfer factor. Ventilation in relation to functional residual volume does not change significantly, whereas distribution of lung perfusion becomes more even, with an increase in the apical lung zones. Immediately after the end of immersion, PaO2 increases rapidly, exceeding the initial value under dry conditions. At the same time, lung perfusion is shifted markedly more towards the basal lung regions, exceeding the gravity-induced blood pooling in the erect subject under dry conditions. The observed changes tend to normalize within 2 min. The changes of respiratory gas exchange during and immediately after immersion can be explained by changes of the inequality of the ventilation-perfusion ratios.", "contents": "Respiratory gas exchange and lung perfusion in man during and after head-out water immersion. The respiratory gas exchange for O2, CO2, and CO has been studied in nine healthy male subjects before, during, and after head-out water immersion. Distribution of lung perfusion and ventilation were determined by quantitative double nuclide scintigraphy (131J and 99mTc) and by argon washout, respectively. The well-known decrease of PaO2 and increase of AaDO2 during immersion is accompanied by a decrease of the CO-transfer factor. Ventilation in relation to functional residual volume does not change significantly, whereas distribution of lung perfusion becomes more even, with an increase in the apical lung zones. Immediately after the end of immersion, PaO2 increases rapidly, exceeding the initial value under dry conditions. At the same time, lung perfusion is shifted markedly more towards the basal lung regions, exceeding the gravity-induced blood pooling in the erect subject under dry conditions. The observed changes tend to normalize within 2 min. The changes of respiratory gas exchange during and immediately after immersion can be explained by changes of the inequality of the ventilation-perfusion ratios."} {"id": "PMID:1273986", "title": "Closed-system habitat for high pressure exposures of animal colonies.", "content": "A deep-diving system has been designed for use with colonies of small rodents at pressures up to 170 ATA. The system consists of a triple-envelope arrangement in which a modular habitat serves as the animal living quarters. The habitat contains provisions for temperature control, gas analysis, and measurement of physical performance and social interaction; it also contains food and water supplies. The surrounding envelope (an acrylic box) is used to control the composition of the gaseous environment presented to the animal colonies. The outermost envelope (a high pressure chamber) maintains the desired pressure conditions. Colonies of five deer mice have been successfully studied at pressures up to 100 ATA. Their performance has been evaluated during 1- to 4-day exposures to various gaseous environments.", "contents": "Closed-system habitat for high pressure exposures of animal colonies. A deep-diving system has been designed for use with colonies of small rodents at pressures up to 170 ATA. The system consists of a triple-envelope arrangement in which a modular habitat serves as the animal living quarters. The habitat contains provisions for temperature control, gas analysis, and measurement of physical performance and social interaction; it also contains food and water supplies. The surrounding envelope (an acrylic box) is used to control the composition of the gaseous environment presented to the animal colonies. The outermost envelope (a high pressure chamber) maintains the desired pressure conditions. Colonies of five deer mice have been successfully studied at pressures up to 100 ATA. Their performance has been evaluated during 1- to 4-day exposures to various gaseous environments."} {"id": "PMID:1273994", "title": "Responses of the cardiovascular system to carotid sinus nerve stimulation.", "content": "The changes in blood pressure, heart rate, cardiac output and blood flow in the femoral and common carotid arteries on carotid sinus nerve stimulation (CSNS) were studied in chloralose anaesthetized dogs, both with spontaneous heart rhythm and during atrial pacing. Stimulation of the sinus nerves with impulse trains and with impulses of constant frequency had almost equal effects on the blood pressure. The former had a greater effect on the heart rate; these findings verified earlier observations. The reductions in cardiac output followed those in heart rate. During atrial pacing the stroke volume was reduced on CSNS. The total peripheral resistance, regional peripheral resistances and input impedance of the vascular bed of the femoral artery were calculated. The initial effects of CSNS varied in relation to the prestimulation total peripheral resistance and to stimulation frequency. Differences between stimulation with a constant frequency and the intermittent types, with the same number of impulses per cardiac cycle, were negligible as regards effects on stroke volume, blood flow and regional vascular resistances. CSNS caused changes in input impedance of the vascular bed of the femoral artery which were very similar to those observed earlier on intraarterial injection of vasodilator drugs. The different effects of intermittent and constant frequency CSNS on the heart rate in dogs with intact vagal nerves and no clamping of the common carotid arteries might be caused by asymmetries in the autonomic effects on the S.A. node. The neurophysiological mechanisms are discussed. It is deduced that greater reductions in blood pressure with intermittent stimulation are only obtained in the pre-existence of a high sympathetic tone.", "contents": "Responses of the cardiovascular system to carotid sinus nerve stimulation. The changes in blood pressure, heart rate, cardiac output and blood flow in the femoral and common carotid arteries on carotid sinus nerve stimulation (CSNS) were studied in chloralose anaesthetized dogs, both with spontaneous heart rhythm and during atrial pacing. Stimulation of the sinus nerves with impulse trains and with impulses of constant frequency had almost equal effects on the blood pressure. The former had a greater effect on the heart rate; these findings verified earlier observations. The reductions in cardiac output followed those in heart rate. During atrial pacing the stroke volume was reduced on CSNS. The total peripheral resistance, regional peripheral resistances and input impedance of the vascular bed of the femoral artery were calculated. The initial effects of CSNS varied in relation to the prestimulation total peripheral resistance and to stimulation frequency. Differences between stimulation with a constant frequency and the intermittent types, with the same number of impulses per cardiac cycle, were negligible as regards effects on stroke volume, blood flow and regional vascular resistances. CSNS caused changes in input impedance of the vascular bed of the femoral artery which were very similar to those observed earlier on intraarterial injection of vasodilator drugs. The different effects of intermittent and constant frequency CSNS on the heart rate in dogs with intact vagal nerves and no clamping of the common carotid arteries might be caused by asymmetries in the autonomic effects on the S.A. node. The neurophysiological mechanisms are discussed. It is deduced that greater reductions in blood pressure with intermittent stimulation are only obtained in the pre-existence of a high sympathetic tone."} {"id": "PMID:1273995", "title": "Thymic diseases as revealed by a series of consecutive thymectomies and biopsies from the thymus.", "content": "A series of 85 thymis biopsies and specimens from thymectomies were re-examined. Forty-five of these were taken from patients with myasthenia gravis. A relatively low frequency of thymitis (57%) was found in these patients, while the frequency of thymoma (9%) was as expected. Two cases of thymitis in thyrotoxicosis were included in the material. In all, 22 thymomas of various kinds (18% of the total material) were diagnosed. A fairly low proportion of these thymomas (18%) were from patients with myasthenia gravis.", "contents": "Thymic diseases as revealed by a series of consecutive thymectomies and biopsies from the thymus. A series of 85 thymis biopsies and specimens from thymectomies were re-examined. Forty-five of these were taken from patients with myasthenia gravis. A relatively low frequency of thymitis (57%) was found in these patients, while the frequency of thymoma (9%) was as expected. Two cases of thymitis in thyrotoxicosis were included in the material. In all, 22 thymomas of various kinds (18% of the total material) were diagnosed. A fairly low proportion of these thymomas (18%) were from patients with myasthenia gravis."} {"id": "PMID:1273996", "title": "Inhibitory effect of dextran 40 upon thrombin-induced fibrin deposition in rat lungs.", "content": "The effect of dextran 40 upon thrombin-induced fibrin deposition in rat lungs was studied. A quantitative method employing isotope-labelled fibrinogen was used to determine the amount of fibrin in the lungs. It was shown that pretreatment was dextran 40 suppressed the accumulation of fibrin in the lungs after injection of thrombin. This was not due to redistribution of the fibrin to other organs but appeared to be a result of decreased intravascular coagulation. It seemed unlikely that the finding could be explained by an effect of dextran upon fibrinolysis.", "contents": "Inhibitory effect of dextran 40 upon thrombin-induced fibrin deposition in rat lungs. The effect of dextran 40 upon thrombin-induced fibrin deposition in rat lungs was studied. A quantitative method employing isotope-labelled fibrinogen was used to determine the amount of fibrin in the lungs. It was shown that pretreatment was dextran 40 suppressed the accumulation of fibrin in the lungs after injection of thrombin. This was not due to redistribution of the fibrin to other organs but appeared to be a result of decreased intravascular coagulation. It seemed unlikely that the finding could be explained by an effect of dextran upon fibrinolysis."} {"id": "PMID:1273997", "title": "Splenectomy--a surgical panorama.", "content": "A five-year material of splenectomies (1970-74) is presented. The material was divided according to the indications for splenectomy as follows: radicality (Group I), iatrogenic hemorrhage Group II), traumatic ruptures (Group III), hematological cases (Group IV) and miscellaneous cases (Group V). There was a large increase in the hematological group over the period due to the addition of splenectomy in the staging procedure for Hodgkin's disease. The mortality was highest in group I and lowest in group IV, as also was the incidence of complications. No patient with Hodgkin's disease died of the operation and the staging laparotomy for this disease, which gives valuable information, thus seems sufficiently safe to warrant routine use.", "contents": "Splenectomy--a surgical panorama. A five-year material of splenectomies (1970-74) is presented. The material was divided according to the indications for splenectomy as follows: radicality (Group I), iatrogenic hemorrhage Group II), traumatic ruptures (Group III), hematological cases (Group IV) and miscellaneous cases (Group V). There was a large increase in the hematological group over the period due to the addition of splenectomy in the staging procedure for Hodgkin's disease. The mortality was highest in group I and lowest in group IV, as also was the incidence of complications. No patient with Hodgkin's disease died of the operation and the staging laparotomy for this disease, which gives valuable information, thus seems sufficiently safe to warrant routine use."} {"id": "PMID:1273998", "title": "Studies on the non-adenomatous glands in patients with a solitary parathyroid adenoma.", "content": "The properties of the non-adenomatous glands in 22 cases of primary hyperparathyroidism due to solitary adenoma were studied. The mean glandular and parenchymal cell weight was somewhat lower than that found by others in glands from euparathyroid subjects. In almost all glands the dark chief cells predominated. This cell type indicates endocrine activity. With some exceptions the glandular endocrine activity seems to be less pronounced than in the concomitantly resected adenoma. Histologically there was no apparent signs of atrophy or hyperplasia in the nonadenomatous glands. The clinical relevance of the findings is discussed.", "contents": "Studies on the non-adenomatous glands in patients with a solitary parathyroid adenoma. The properties of the non-adenomatous glands in 22 cases of primary hyperparathyroidism due to solitary adenoma were studied. The mean glandular and parenchymal cell weight was somewhat lower than that found by others in glands from euparathyroid subjects. In almost all glands the dark chief cells predominated. This cell type indicates endocrine activity. With some exceptions the glandular endocrine activity seems to be less pronounced than in the concomitantly resected adenoma. Histologically there was no apparent signs of atrophy or hyperplasia in the nonadenomatous glands. The clinical relevance of the findings is discussed."} {"id": "PMID:1273999", "title": "The concordance of respiratory fluctuations in oesophageal and central venous pressures.", "content": "Respiratory fluctuations in oesophageal and central venous pressures were recorded in 13 healthy subjects and compared with respect to phase and amplitude concordance. An average divergence in phase of nearly 180 degrees was obtained, with large inter-individual variations. Disregarding phase the amplitude of the respiratory central venous pressure was found to be, on the average, a good 1/4 of that of the oesophageal pressure in the supine posture, and a good 2/3 while the subjects were sitting. These figures also varied considerably. It is suggested that the findings might be referred to competition between a central venous pressure raising effect of inspiration enhanced venous return, and a central venous pressure depressing effect of the inspiratory fall in intrathoracic pressure. The partitioning of costal and abdomino-diaphragmatic breathing is considered of great significance to the outcome of this competition. It is concluded that the oesophageal balloon catheter technique for estimation of transpulmonary pressure cannot simply be replaced by the central venous catheter technique in healthy subjects. Its application in patients with certain pulmonary disorders, however, might be more successful.", "contents": "The concordance of respiratory fluctuations in oesophageal and central venous pressures. Respiratory fluctuations in oesophageal and central venous pressures were recorded in 13 healthy subjects and compared with respect to phase and amplitude concordance. An average divergence in phase of nearly 180 degrees was obtained, with large inter-individual variations. Disregarding phase the amplitude of the respiratory central venous pressure was found to be, on the average, a good 1/4 of that of the oesophageal pressure in the supine posture, and a good 2/3 while the subjects were sitting. These figures also varied considerably. It is suggested that the findings might be referred to competition between a central venous pressure raising effect of inspiration enhanced venous return, and a central venous pressure depressing effect of the inspiratory fall in intrathoracic pressure. The partitioning of costal and abdomino-diaphragmatic breathing is considered of great significance to the outcome of this competition. It is concluded that the oesophageal balloon catheter technique for estimation of transpulmonary pressure cannot simply be replaced by the central venous catheter technique in healthy subjects. Its application in patients with certain pulmonary disorders, however, might be more successful."} {"id": "PMID:1274000", "title": "Acute pancreatitis and hepatic necrosis in the acute afferent loop syndrome. A histopathological study in the rat.", "content": "The morphological changes in the liver and pancreas during the first 12 hours in the acute afferent loop syndrome were studied in rats with a Billroth II gastric resection. Two essentially different types of changes were found in the pancreas. One was a coagulative necrosis without an inflammatory reaction, which has been found after instillation of bile, bile salts and the detergent sodium lauryl sulphate into the pancreatic ducts. The other type of pancreatitis was an intense, acute purulent inflammation often with bacteria visible in the histological sections. In the liver, large areas of necrosis were often encountered, sometimes mixed with polymorphonuclear leukocytes and bacteria, in a few cases combined with thrombi in small portal veins. The changes in the pancreas occurred very rapidly; only 4 hours after occlusion of the afferent loop there were signs of pancreatitis in some cases and 12 hours after occlusion there was an acute pancreatitis in all cases.", "contents": "Acute pancreatitis and hepatic necrosis in the acute afferent loop syndrome. A histopathological study in the rat. The morphological changes in the liver and pancreas during the first 12 hours in the acute afferent loop syndrome were studied in rats with a Billroth II gastric resection. Two essentially different types of changes were found in the pancreas. One was a coagulative necrosis without an inflammatory reaction, which has been found after instillation of bile, bile salts and the detergent sodium lauryl sulphate into the pancreatic ducts. The other type of pancreatitis was an intense, acute purulent inflammation often with bacteria visible in the histological sections. In the liver, large areas of necrosis were often encountered, sometimes mixed with polymorphonuclear leukocytes and bacteria, in a few cases combined with thrombi in small portal veins. The changes in the pancreas occurred very rapidly; only 4 hours after occlusion of the afferent loop there were signs of pancreatitis in some cases and 12 hours after occlusion there was an acute pancreatitis in all cases."} {"id": "PMID:1274001", "title": "Treatment of extensive renal calculi with extracorporeal surgery and autotransplantation.", "content": "Two patients with large calculi in solitary kidneys, treated by ex vivo stone extraction and autotransplantation, are presented. The results show this to be a valuable therapeutic modality for difficult renal calculi where an in situ approach would be hazardous.", "contents": "Treatment of extensive renal calculi with extracorporeal surgery and autotransplantation. Two patients with large calculi in solitary kidneys, treated by ex vivo stone extraction and autotransplantation, are presented. The results show this to be a valuable therapeutic modality for difficult renal calculi where an in situ approach would be hazardous."} {"id": "PMID:1274002", "title": "Multilocular cystic kidney.", "content": "Two cases of multilocular cystic kidney are reported. Current concepts of pathogenesis are reviewed. Treatment by total nephrectomy is advocated when the contralateral kidney is normal; partial nephrectomy should be reserved for those cases in which the contralateral kidney has reduced function or is absent.", "contents": "Multilocular cystic kidney. Two cases of multilocular cystic kidney are reported. Current concepts of pathogenesis are reviewed. Treatment by total nephrectomy is advocated when the contralateral kidney is normal; partial nephrectomy should be reserved for those cases in which the contralateral kidney has reduced function or is absent."} {"id": "PMID:1274003", "title": "Renin-dependent hypertension in children with reflux nephropathy.", "content": "In children with reflux nephropathy renin-dependent hypertension may develop. Two girls with reflux nephropathy, hypertension, elevated plasma renin activity, but normal (Case I) and near normal (Case 2) serum creatinines are described. These cases suggest that reflux nephropathy can activate the renin-angiotensin system and that the renin inhibitors, methyldopa and propranolol, an useful in managing this type of hypertension.", "contents": "Renin-dependent hypertension in children with reflux nephropathy. In children with reflux nephropathy renin-dependent hypertension may develop. Two girls with reflux nephropathy, hypertension, elevated plasma renin activity, but normal (Case I) and near normal (Case 2) serum creatinines are described. These cases suggest that reflux nephropathy can activate the renin-angiotensin system and that the renin inhibitors, methyldopa and propranolol, an useful in managing this type of hypertension."} {"id": "PMID:1274004", "title": "Congenital hydronephrosis of lower segment in duplex kidney.", "content": "Congenital hydronephrosis of the lower segment in duplex kidney was treated in 12 patients. This uncommon abnormality carries the risk of calculous formation, chronic urinary tract infection, and functional failure of the involved segment. Diagnostic problems encountered included differentiation from tumor, obstruction by a calculus, and hydronephrosis due to reflux. Treatment was individualized according to severity of hydronephrosis and presence or absence of specific complications. Mild obstruction could be treated nonsurgically while the patient was closely observed for evidence of stone, infection, or worsening of obstruction. Available surgical procedures include end to side or side to side pyeloureteral anastomosis, plastic widening of a narrowed obstructive site, removal of calculus with relief of obstruction, and heminephrectomy.", "contents": "Congenital hydronephrosis of lower segment in duplex kidney. Congenital hydronephrosis of the lower segment in duplex kidney was treated in 12 patients. This uncommon abnormality carries the risk of calculous formation, chronic urinary tract infection, and functional failure of the involved segment. Diagnostic problems encountered included differentiation from tumor, obstruction by a calculus, and hydronephrosis due to reflux. Treatment was individualized according to severity of hydronephrosis and presence or absence of specific complications. Mild obstruction could be treated nonsurgically while the patient was closely observed for evidence of stone, infection, or worsening of obstruction. Available surgical procedures include end to side or side to side pyeloureteral anastomosis, plastic widening of a narrowed obstructive site, removal of calculus with relief of obstruction, and heminephrectomy."} {"id": "PMID:1274005", "title": "In vitro cytotoxicity studies in bladder and renal cell cancer.", "content": "Attempts to obtain cell lines from bladder and renal cancer patients were done in 42 patients, with success to obtain primary cultures in 25 and long-term cultures in 7. Cell-mediated and humoral immunity was demonstrated in both tumors by microcytotoxicity in vitro. No cytotoxicity could be deomonstrated against target cells obtained from metastatic cancer tissue. Abrogation of cell-mediated immunity by serum factors was demonstrated. No recurrence was obtained in the group of patients showing positive lymphocytotoxicity during follow-up.", "contents": "In vitro cytotoxicity studies in bladder and renal cell cancer. Attempts to obtain cell lines from bladder and renal cancer patients were done in 42 patients, with success to obtain primary cultures in 25 and long-term cultures in 7. Cell-mediated and humoral immunity was demonstrated in both tumors by microcytotoxicity in vitro. No cytotoxicity could be deomonstrated against target cells obtained from metastatic cancer tissue. Abrogation of cell-mediated immunity by serum factors was demonstrated. No recurrence was obtained in the group of patients showing positive lymphocytotoxicity during follow-up."} {"id": "PMID:1274006", "title": "Management of neoplasms in vesical diverticula.", "content": "Two cases of neoplasms occurring in vesical diverticula are presented, and the pertinent literature is reviewed. It is suggested that a patient with a neoplasm in a vesical diverticulum be staged by surgical exploration and be accorded the same aggressive management as any patient with an infiltrating vesical neoplasm.", "contents": "Management of neoplasms in vesical diverticula. Two cases of neoplasms occurring in vesical diverticula are presented, and the pertinent literature is reviewed. It is suggested that a patient with a neoplasm in a vesical diverticulum be staged by surgical exploration and be accorded the same aggressive management as any patient with an infiltrating vesical neoplasm."} {"id": "PMID:1274007", "title": "Anterior bladder tube in radical retropubic prostatectomy.", "content": "Six patients with a minimum of ten months' follow-up have undergone reconstruction of the urethra by anterior bladder tube after radical retropubic prostatectomy; 4 void well and are continent, 1 is incontinent, and 1 has severe stricture.", "contents": "Anterior bladder tube in radical retropubic prostatectomy. Six patients with a minimum of ten months' follow-up have undergone reconstruction of the urethra by anterior bladder tube after radical retropubic prostatectomy; 4 void well and are continent, 1 is incontinent, and 1 has severe stricture."} {"id": "PMID:1274008", "title": "Cefazolin and cephalexin levels in prostatic tissue and sera.", "content": "A study was carried out on 18 patients given cefazolin intramuscularly and 17 patients given cephalexin by mouth preoperatively prior to transurethral resection of the prostate. Prostatic tissue and serum levels of the two drugs were determined and contrasted with previously reported mean inhibitory concentrations. It was found that cefazolin was present in the sera and prostatic tissues in levels greater than was cephalexin and that cefazolin frequently exceeded the minimum inhibitory concentrations necessary for sensitive organisms to be affected, whereas cephalexin did not. Therefore, it would appear that cefazolin would be preferable to cephalexin in treatment of acute bacterial prostatitis.", "contents": "Cefazolin and cephalexin levels in prostatic tissue and sera. A study was carried out on 18 patients given cefazolin intramuscularly and 17 patients given cephalexin by mouth preoperatively prior to transurethral resection of the prostate. Prostatic tissue and serum levels of the two drugs were determined and contrasted with previously reported mean inhibitory concentrations. It was found that cefazolin was present in the sera and prostatic tissues in levels greater than was cephalexin and that cefazolin frequently exceeded the minimum inhibitory concentrations necessary for sensitive organisms to be affected, whereas cephalexin did not. Therefore, it would appear that cefazolin would be preferable to cephalexin in treatment of acute bacterial prostatitis."} {"id": "PMID:1274009", "title": "Bacterial prostatitis: treatment with trimethoprim-sulfamethoxazole.", "content": "Fifteen patients with chronic bacterial prostatitis were treated with trimethoprim-sulfamethoxazole for three months. In 60 per cent of the patients a recurrence of chronic bacterial prostatitis developed during a follow-up period of from one to two and one-half years. It appears that factors other than a diffusion barrier to effective antimicrobial agents into the prostatic gland are responsible for the persistence of chronic bacterial infections of the prostate.", "contents": "Bacterial prostatitis: treatment with trimethoprim-sulfamethoxazole. Fifteen patients with chronic bacterial prostatitis were treated with trimethoprim-sulfamethoxazole for three months. In 60 per cent of the patients a recurrence of chronic bacterial prostatitis developed during a follow-up period of from one to two and one-half years. It appears that factors other than a diffusion barrier to effective antimicrobial agents into the prostatic gland are responsible for the persistence of chronic bacterial infections of the prostate."} {"id": "PMID:1274010", "title": "Paraurethral cysts in female neonate.", "content": "Paraurethral cysts in the female neonate are uncommon lesions. All reported cases have either ruptured spontaneously or responded to simple marsupialization. However, complete urologic evaluation is mandatory because they simulate ectopic ureteroceles in appearance. Herein is reported our experience with 5 patients. The etiology, embryogenesis, natural history, differential diagnosis, and treatment are discussed.", "contents": "Paraurethral cysts in female neonate. Paraurethral cysts in the female neonate are uncommon lesions. All reported cases have either ruptured spontaneously or responded to simple marsupialization. However, complete urologic evaluation is mandatory because they simulate ectopic ureteroceles in appearance. Herein is reported our experience with 5 patients. The etiology, embryogenesis, natural history, differential diagnosis, and treatment are discussed."} {"id": "PMID:1274011", "title": "High renin hypertension associated with renal cortical cyst.", "content": "A fifty-seven-year-old patient with a five to one elevation of right renal vein plasma renin activity associated with a large, simple cortical cyst of the right lower pole is presented. Marsupialization of the cyst was associated with improvement in the patient's hypertension and the finding of bilaterally equal renal vein renin activity three months postoperatively. Possible mechanisms for hypertension are discussed in context of the experimental models of Goldblatt and Page in such lesions as cortical cysts of large size causing hydronephrosis, vascular stretching, or renal parenchymal compression.", "contents": "High renin hypertension associated with renal cortical cyst. A fifty-seven-year-old patient with a five to one elevation of right renal vein plasma renin activity associated with a large, simple cortical cyst of the right lower pole is presented. Marsupialization of the cyst was associated with improvement in the patient's hypertension and the finding of bilaterally equal renal vein renin activity three months postoperatively. Possible mechanisms for hypertension are discussed in context of the experimental models of Goldblatt and Page in such lesions as cortical cysts of large size causing hydronephrosis, vascular stretching, or renal parenchymal compression."} {"id": "PMID:1274012", "title": "Papillary renal cell carcinoma six years after renal cystectomy.", "content": "A papillary renal cell carcinoma developed in this patient in the same position that six years previously had undergone unroofing of a benign cyst. The discussion includes a brief review of the relationship between renal cyst and carcinoma.", "contents": "Papillary renal cell carcinoma six years after renal cystectomy. A papillary renal cell carcinoma developed in this patient in the same position that six years previously had undergone unroofing of a benign cyst. The discussion includes a brief review of the relationship between renal cyst and carcinoma."} {"id": "PMID:1274013", "title": "Recurrent partial priapism.", "content": "Exploration of an unusual case of a painful, recurrent, perineal mass revealed partial priapism of the right corpora cavernosa. Etiology is speculative and no definitive therapy is offered.", "contents": "Recurrent partial priapism. Exploration of an unusual case of a painful, recurrent, perineal mass revealed partial priapism of the right corpora cavernosa. Etiology is speculative and no definitive therapy is offered."} {"id": "PMID:1274014", "title": "Ureteritis cystica after treatment of cyclophosphamide-induced hemorrhagic cystitis.", "content": "A case is presented in which ureteritis cystica developed following formalin instillation for treatment of cyclophosphamide-induced hemorrhagic cystitis. It is not known whether this complication, not previously reported, is a result of the cyclophosphamide, the formalin, or a combination of both. Patients being considered for formalin instillation should be studied by cystography for evaluation of vesicoureteral reflux. Alternative methods to formalin instillation should be considered in patients with reflux.", "contents": "Ureteritis cystica after treatment of cyclophosphamide-induced hemorrhagic cystitis. A case is presented in which ureteritis cystica developed following formalin instillation for treatment of cyclophosphamide-induced hemorrhagic cystitis. It is not known whether this complication, not previously reported, is a result of the cyclophosphamide, the formalin, or a combination of both. Patients being considered for formalin instillation should be studied by cystography for evaluation of vesicoureteral reflux. Alternative methods to formalin instillation should be considered in patients with reflux."} {"id": "PMID:1274016", "title": "Cystic changes in adult human kidneys after ureteral obstruction: microdissection studies.", "content": "Five kidneys from patients suffering from ureteral obstruction were selected for the study; from each, 100 nephrons and 20 collecting ducts were studied using Darmady's microdissection technique. Whereas three kidneys showed macroscopic cysts, microscopically, all kidneys displayed dilation and diverticulation of the nephrons particularly of the loop of Henl\u00e9 and of distal convoluted tubules. Some dilatation of the collecting ducts was also noticed.", "contents": "Cystic changes in adult human kidneys after ureteral obstruction: microdissection studies. Five kidneys from patients suffering from ureteral obstruction were selected for the study; from each, 100 nephrons and 20 collecting ducts were studied using Darmady's microdissection technique. Whereas three kidneys showed macroscopic cysts, microscopically, all kidneys displayed dilation and diverticulation of the nephrons particularly of the loop of Henl\u00e9 and of distal convoluted tubules. Some dilatation of the collecting ducts was also noticed."} {"id": "PMID:1274018", "title": "Chronically infected and postdiversionary bladders: cytologic and histopathologic study.", "content": "Cytologic and histopathologic study of 36 patients demonstrated an 86 to 92 per cent incidence of squamous metaplasia of the bladder among patients with chronically infected bladders and a 64 per cent incidence in patients with postdiversionary bladders left behind. The relationships of infection, inflammation, squamous meetaplasia, and squamous cell carcinoma of the bladder are reviewed. It is postulated that the same carcinogenic factors which induce transitional cell carcinoma might cause squamous cell carcinoma if the epithelium had previously undergone squamous metaplasia.", "contents": "Chronically infected and postdiversionary bladders: cytologic and histopathologic study. Cytologic and histopathologic study of 36 patients demonstrated an 86 to 92 per cent incidence of squamous metaplasia of the bladder among patients with chronically infected bladders and a 64 per cent incidence in patients with postdiversionary bladders left behind. The relationships of infection, inflammation, squamous meetaplasia, and squamous cell carcinoma of the bladder are reviewed. It is postulated that the same carcinogenic factors which induce transitional cell carcinoma might cause squamous cell carcinoma if the epithelium had previously undergone squamous metaplasia."} {"id": "PMID:1274019", "title": "Penile metastases from bronchogenic carcinoma.", "content": "A case of secondary penile carcinoma originating in the lung is reported. Modes of metastases to the penis, treatment, prognosis, and a brief review of the literature are given.", "contents": "Penile metastases from bronchogenic carcinoma. A case of secondary penile carcinoma originating in the lung is reported. Modes of metastases to the penis, treatment, prognosis, and a brief review of the literature are given."} {"id": "PMID:1274020", "title": "Cytology of transitional cell carcinoma in situ of urinary bladder with extensive prostatic involvement.", "content": "Cytologic differences in the urine of 6 patients with transitional cell carcinoma in situ (CIS) of the urinary bladder with and without prostatic duct involvement are described. In the former group, there was an admixture of CIS cells along with many bizarre malignant cells which increased with time and showed malignant criteria indicative of changes more than CIS alone.", "contents": "Cytology of transitional cell carcinoma in situ of urinary bladder with extensive prostatic involvement. Cytologic differences in the urine of 6 patients with transitional cell carcinoma in situ (CIS) of the urinary bladder with and without prostatic duct involvement are described. In the former group, there was an admixture of CIS cells along with many bizarre malignant cells which increased with time and showed malignant criteria indicative of changes more than CIS alone."} {"id": "PMID:1274022", "title": "Unusual presentations of hypernephroma.", "content": "Two cases with varying presentations of renal adenocarcinoma are reviewed. The first patient manifested an unsuspected hypernephroma on intravenous pyelogram for ureteral colic by demonstrating a distorted collecting system and peripelvic extravasation of contrast material. The second case report is one of spontaneous subcapsular renal hemorrhage with hypernephroma.", "contents": "Unusual presentations of hypernephroma. Two cases with varying presentations of renal adenocarcinoma are reviewed. The first patient manifested an unsuspected hypernephroma on intravenous pyelogram for ureteral colic by demonstrating a distorted collecting system and peripelvic extravasation of contrast material. The second case report is one of spontaneous subcapsular renal hemorrhage with hypernephroma."} {"id": "PMID:1274023", "title": "Congenital renal dysplasia: Osathanondh-Potter type ii polycystic kidneys.", "content": "Congenital renal dysplasia represents a group of nonhereditary kidney malformations frequently encountered in infants and children. The dysplasia may involve one or both kidneys totally or segmentally. The clinical presentation and prognosis depend on the extent of renal involvement and further development of the dysplastic renal tissue as well as the severity of coexisting malformations in other organs. The unifying factor in each instance is the characteristic histologic appearance of the dysplastic renal tissue. Congenital multicystic kidney and multilocular renal cyst are the best known members of the group. Radiologic features in conjunction with the clinical picture can suggest the correct diagnosis in most cases.", "contents": "Congenital renal dysplasia: Osathanondh-Potter type ii polycystic kidneys. Congenital renal dysplasia represents a group of nonhereditary kidney malformations frequently encountered in infants and children. The dysplasia may involve one or both kidneys totally or segmentally. The clinical presentation and prognosis depend on the extent of renal involvement and further development of the dysplastic renal tissue as well as the severity of coexisting malformations in other organs. The unifying factor in each instance is the characteristic histologic appearance of the dysplastic renal tissue. Congenital multicystic kidney and multilocular renal cyst are the best known members of the group. Radiologic features in conjunction with the clinical picture can suggest the correct diagnosis in most cases."} {"id": "PMID:1274024", "title": "Renal cell carcinoma masquerading as obstructive uropathy.", "content": "A case of renal cell carcinoma without renal vein involvement is presented in which the intravenous urogram demonstrated only a persistent nephrogram suggestive of obstructive uropathy.", "contents": "Renal cell carcinoma masquerading as obstructive uropathy. A case of renal cell carcinoma without renal vein involvement is presented in which the intravenous urogram demonstrated only a persistent nephrogram suggestive of obstructive uropathy."} {"id": "PMID:1274025", "title": "Electromyographic and gas urethral pressure profile.", "content": "A new technique for recording urethral pressure profile is described. The method consists of a simultaneous combined electromyographic and gas urethral pressure profile recording. Normal and pathologic patterns are described. The method provides information on the correlation between intraurethral pressure and activity in the periurethral striated musculature and has proved useful in the assessment of neurologic dysfunction of the urethra.", "contents": "Electromyographic and gas urethral pressure profile. A new technique for recording urethral pressure profile is described. The method consists of a simultaneous combined electromyographic and gas urethral pressure profile recording. Normal and pathologic patterns are described. The method provides information on the correlation between intraurethral pressure and activity in the periurethral striated musculature and has proved useful in the assessment of neurologic dysfunction of the urethra."} {"id": "PMID:1274028", "title": "Intraocular lenses: complications, complication factors, and adverse conditions in lens implantation surgery.", "content": "During the surgical act of lens implantation a fairly large number of minor and major complications are a result of inexperience of the surgeon. Some of them are due to ill-advised attempts to insert lenses in difficult cases. Most complications can be prevented by following a number of basic surgical rules for lens implantation.", "contents": "Intraocular lenses: complications, complication factors, and adverse conditions in lens implantation surgery. During the surgical act of lens implantation a fairly large number of minor and major complications are a result of inexperience of the surgeon. Some of them are due to ill-advised attempts to insert lenses in difficult cases. Most complications can be prevented by following a number of basic surgical rules for lens implantation."} {"id": "PMID:1274031", "title": "Retinal accidents in pseudophakia--intracapsular vs extracapsular surgery.", "content": "A follow-up of 120 pseudophakic eyes of 85 patients that underwent surgery for senile cataract showed a definite superiority of extracapsular surgery over intracapsular surgery as far as the longterm fate of the retina concerns. Comparable series have been chosen. Retinal detachment did not occur in extracapsular eyes that never had posterior capsulotomy, and occurred most often after intracapsular surgery. Signs of previous or existing maculopathy were searched for with the usual tests (funduscopy, visual acuity, Amsler test) and moreover with Haidinger's brushes test. The macula turned out to have least suffered after extracapsular surgery without capsulotomy and most after intracapsular surgery. Haidinger's brushes test is a valuable tool for the detection of postoperative macular edema.", "contents": "Retinal accidents in pseudophakia--intracapsular vs extracapsular surgery. A follow-up of 120 pseudophakic eyes of 85 patients that underwent surgery for senile cataract showed a definite superiority of extracapsular surgery over intracapsular surgery as far as the longterm fate of the retina concerns. Comparable series have been chosen. Retinal detachment did not occur in extracapsular eyes that never had posterior capsulotomy, and occurred most often after intracapsular surgery. Signs of previous or existing maculopathy were searched for with the usual tests (funduscopy, visual acuity, Amsler test) and moreover with Haidinger's brushes test. The macula turned out to have least suffered after extracapsular surgery without capsulotomy and most after intracapsular surgery. Haidinger's brushes test is a valuable tool for the detection of postoperative macular edema."} {"id": "PMID:1274035", "title": "Late hyphema due to wound vascularization.", "content": "In 1972 I reported that focal deep vascularization of the stromal wound may lead to hyphema months or years after cataract surgery. It results from ingrowth of episcleral vessels which terminate in capillaries at the inner edge of the incision site. Blurred vision occurring spontaneously or following minimal trauma, or physical strain is the primary symptom. Minimal episodes of bleeding are easily overlooked or mistaken for iridocyclitis. Gonioscopy usually reveals a small clump of vessels or the actual bleeding site. The trauma of the gonioscopy may precipitate bleeding.", "contents": "Late hyphema due to wound vascularization. In 1972 I reported that focal deep vascularization of the stromal wound may lead to hyphema months or years after cataract surgery. It results from ingrowth of episcleral vessels which terminate in capillaries at the inner edge of the incision site. Blurred vision occurring spontaneously or following minimal trauma, or physical strain is the primary symptom. Minimal episodes of bleeding are easily overlooked or mistaken for iridocyclitis. Gonioscopy usually reveals a small clump of vessels or the actual bleeding site. The trauma of the gonioscopy may precipitate bleeding."} {"id": "PMID:1274036", "title": "Cataract extraction by the intracapsular methods and by phacoemulsification: the results of surgeons in training.", "content": "The results of 63 phacoemulsifications performed by 14 resident ophthalmologists (surgeons in training) were compared to their first 112 intracapsular cataract procedures. Although the number of complications was greater in the eyes undergoing intracapsular operations, the final visual acuities obtained by either procedurewere similar: visual acuities in the range of 20/20 to 20/30 were found in 80.7% of intracapsular cataract operations and in 83.3% of phacoemulsification procedures. Visual acuities of 20/50 or better were found in 90.3% of intracapsular cataract extractions andin 88.8% of phacoemulsification procedures. Cylindric correction of higher power was required to correct astigmatism associated with intracapsular cataract surgery as compared to phacoemulsification. The results of irrigation-aspiration of soft or traumatic cataracts performed in 20 eyes with needle and syringe were compared to results of 19 eyes operated on by use of the Cavitron-Kelman irrigation-aspiration handpiece. The incidence of postoperative secondary membrane requiring discussion was similar for both procedures. The basis for setting up a successful program for resident training in phacoemulsification is discussed.", "contents": "Cataract extraction by the intracapsular methods and by phacoemulsification: the results of surgeons in training. The results of 63 phacoemulsifications performed by 14 resident ophthalmologists (surgeons in training) were compared to their first 112 intracapsular cataract procedures. Although the number of complications was greater in the eyes undergoing intracapsular operations, the final visual acuities obtained by either procedurewere similar: visual acuities in the range of 20/20 to 20/30 were found in 80.7% of intracapsular cataract operations and in 83.3% of phacoemulsification procedures. Visual acuities of 20/50 or better were found in 90.3% of intracapsular cataract extractions andin 88.8% of phacoemulsification procedures. Cylindric correction of higher power was required to correct astigmatism associated with intracapsular cataract surgery as compared to phacoemulsification. The results of irrigation-aspiration of soft or traumatic cataracts performed in 20 eyes with needle and syringe were compared to results of 19 eyes operated on by use of the Cavitron-Kelman irrigation-aspiration handpiece. The incidence of postoperative secondary membrane requiring discussion was similar for both procedures. The basis for setting up a successful program for resident training in phacoemulsification is discussed."} {"id": "PMID:1274038", "title": "New dimensions in ocular pharmacology 1975.", "content": "Progress is painful. This is certainly true in drug therapy. No drug in clinical use is devoid of toxicity, and all ophthalmologists are aware that no human being should be exposed to needless risk. On the other hand, the potential harm done to present and future generations by lack of adequate therapy for many diseases makes it imperative that new drugs, despite their associated hazards,continue to be introduced into research and practice. If an ophthalmologist accepts these thoughts, he also must accept a commitment to understand the effect of drugs in disease, the predisposing factors leading to drug reactions and interactions, the effect of disease on drugs, before he uses them.", "contents": "New dimensions in ocular pharmacology 1975. Progress is painful. This is certainly true in drug therapy. No drug in clinical use is devoid of toxicity, and all ophthalmologists are aware that no human being should be exposed to needless risk. On the other hand, the potential harm done to present and future generations by lack of adequate therapy for many diseases makes it imperative that new drugs, despite their associated hazards,continue to be introduced into research and practice. If an ophthalmologist accepts these thoughts, he also must accept a commitment to understand the effect of drugs in disease, the predisposing factors leading to drug reactions and interactions, the effect of disease on drugs, before he uses them."} {"id": "PMID:1274096", "title": "[Extracorporeal fixation of liver slices onto the system of \"artificial kidney\" apparatus].", "content": "On 36 experimental dogs a new dialyser \"liver-kidney\" was tested, in which along with the process of dialysis some functions of the liver were carried out on account of placing in the apparatus homologous liver slices 2-3 mm thick. The data of biochemical studies of animals blood have evidenced satisfactory results. The dialyser with heteroliver slices assisted in two patients with hepato-renal failure. One of them made a good recovery and was discharged from the clinic, a favourable immediate result was obtained in the second patient.", "contents": "[Extracorporeal fixation of liver slices onto the system of \"artificial kidney\" apparatus]. On 36 experimental dogs a new dialyser \"liver-kidney\" was tested, in which along with the process of dialysis some functions of the liver were carried out on account of placing in the apparatus homologous liver slices 2-3 mm thick. The data of biochemical studies of animals blood have evidenced satisfactory results. The dialyser with heteroliver slices assisted in two patients with hepato-renal failure. One of them made a good recovery and was discharged from the clinic, a favourable immediate result was obtained in the second patient."} {"id": "PMID:1274097", "title": "[Changes of certain indicators of gas exchange and hemodynamics under conditions of long-term peridural anesthesia after lung resection].", "content": "A continuous peridural anesthesia after pulmonary resection was conducted in 200 patients aged from 3 to 72 years. The anesthesia would contribute to a prompt normalization of ventilatory indices and acid-base balance in early terms, it also improves hemodynamics. This method of postoperative anesthesia enabled the authors to reduce the number of tracheobronchial obturations in the surgical department from 8.4% to 5.1%.", "contents": "[Changes of certain indicators of gas exchange and hemodynamics under conditions of long-term peridural anesthesia after lung resection]. A continuous peridural anesthesia after pulmonary resection was conducted in 200 patients aged from 3 to 72 years. The anesthesia would contribute to a prompt normalization of ventilatory indices and acid-base balance in early terms, it also improves hemodynamics. This method of postoperative anesthesia enabled the authors to reduce the number of tracheobronchial obturations in the surgical department from 8.4% to 5.1%."} {"id": "PMID:1274098", "title": "[Selection of surgical method in aortic coarctation].", "content": "An experience with 64 operations for aortic coarctation is summarized. The author suggests some simple mathematical calculations allowing in each particular case a selection of an optimum variant of surgical intervention. The main task is to restore a normal diameter of the aorta. Of 64 operated subjects 2 patients died, both of them were operated upon in later terms.", "contents": "[Selection of surgical method in aortic coarctation]. An experience with 64 operations for aortic coarctation is summarized. The author suggests some simple mathematical calculations allowing in each particular case a selection of an optimum variant of surgical intervention. The main task is to restore a normal diameter of the aorta. Of 64 operated subjects 2 patients died, both of them were operated upon in later terms."} {"id": "PMID:1274105", "title": "[Postoperative chondritis and osteomyelitis of the ribs and sternum].", "content": "Postoperative chondritis and osteomyelitis of the ribs and sternum were observed in 90 of 4620 operated patients. The main causes contributing to the development of this complication are errors in treatment of cartilages during thoracotomy and suppurative complications in the pleural cavity or in the operative wound. A radical removal of the affected costal and sternal portions as early as possible is considered to be the method of choice in treatment of chondirtis and osteomyelitis of the ribs and sternum.", "contents": "[Postoperative chondritis and osteomyelitis of the ribs and sternum]. Postoperative chondritis and osteomyelitis of the ribs and sternum were observed in 90 of 4620 operated patients. The main causes contributing to the development of this complication are errors in treatment of cartilages during thoracotomy and suppurative complications in the pleural cavity or in the operative wound. A radical removal of the affected costal and sternal portions as early as possible is considered to be the method of choice in treatment of chondirtis and osteomyelitis of the ribs and sternum."} {"id": "PMID:1274106", "title": "[Comparative characteristics of the methods of management of the pleural cavity in nonspecific empyema].", "content": "The author failed to reveal some essential advantages of any of five methods employed for sanation of the pleural cavity in empyema. The method of active aspiration and irrigation of the cavity with antiseptic and antibiotic solutions is felt to be mostly rational.", "contents": "[Comparative characteristics of the methods of management of the pleural cavity in nonspecific empyema]. The author failed to reveal some essential advantages of any of five methods employed for sanation of the pleural cavity in empyema. The method of active aspiration and irrigation of the cavity with antiseptic and antibiotic solutions is felt to be mostly rational."} {"id": "PMID:1274107", "title": "[Tracheobronchography in patients with pleuro-pulmonary complications after lung resection].", "content": "Tracheobronchography was performed in 79 patients with different bronchopleural complications after lung resection. In 38 of 42 patients with pleural empyema the presence of bronchial or bronchiolar fistula was found, residual pleural or pleuropulmonary cavities were noted in 24 patients, recurrent tuberculosis or bronchiectases--in 13. The results obtained in contrast investigation of the tracheobronchial tree allowed a proper selection of the method of treatment for different complications, a determination of the extent of a reoperation and prevention of recurrent complications following the repeat surgery.", "contents": "[Tracheobronchography in patients with pleuro-pulmonary complications after lung resection]. Tracheobronchography was performed in 79 patients with different bronchopleural complications after lung resection. In 38 of 42 patients with pleural empyema the presence of bronchial or bronchiolar fistula was found, residual pleural or pleuropulmonary cavities were noted in 24 patients, recurrent tuberculosis or bronchiectases--in 13. The results obtained in contrast investigation of the tracheobronchial tree allowed a proper selection of the method of treatment for different complications, a determination of the extent of a reoperation and prevention of recurrent complications following the repeat surgery."} {"id": "PMID:1274108", "title": "[Aftereffects of long-term stay of foreign bodies in the bronchi].", "content": "The author have observed 132 patients with foreign bodies in the bronchi. In 32 of them foreign bodies have been staying in the bronchi for 1 day and longer (up to 24 years). Pathological changes in the lung due to the presence of foreign bodies in the bronchi and the rational therapy are described.", "contents": "[Aftereffects of long-term stay of foreign bodies in the bronchi]. The author have observed 132 patients with foreign bodies in the bronchi. In 32 of them foreign bodies have been staying in the bronchi for 1 day and longer (up to 24 years). Pathological changes in the lung due to the presence of foreign bodies in the bronchi and the rational therapy are described."} {"id": "PMID:1274110", "title": "[Multiple peptic ulcers complicated by perforation and profuse hemorrhage].", "content": "Among 65 patients with ulcer perforation in the abdominal cavity and profuse gastroduodenal hemorrhage in 11 patients (16.9%) multiple and complicated ulcers were observed. In 4 patients multiple ulcers with perforation and hemorrhage were revealed during the operative procedure, in 2--only in reoperation and in 5--at autopsy. Of 11 subjects under observation 7 patients died. After an early extensive resection 4 patients made a recovery.", "contents": "[Multiple peptic ulcers complicated by perforation and profuse hemorrhage]. Among 65 patients with ulcer perforation in the abdominal cavity and profuse gastroduodenal hemorrhage in 11 patients (16.9%) multiple and complicated ulcers were observed. In 4 patients multiple ulcers with perforation and hemorrhage were revealed during the operative procedure, in 2--only in reoperation and in 5--at autopsy. Of 11 subjects under observation 7 patients died. After an early extensive resection 4 patients made a recovery."} {"id": "PMID:1274112", "title": "[Surgical treatment of post-thrombophlebitic syndrome].", "content": "Under observation were 125 patients with postthrombophlebitic syndrome of the lower extremities. Along with the routine surgical methods of treatment the authors suggested and performed in 30 patients a new operative procedure--communicotomy, that consists in separation of the superficial and profound venous systems in the lower crural third via a separate incision in the upper crural third. To this end a new instrument--a communicotome was devised. Indications to some or other kind of surgery were elaborated by the authors. 76% of patients showed an improvement within the terms from 1 to 6 years postoperatively.", "contents": "[Surgical treatment of post-thrombophlebitic syndrome]. Under observation were 125 patients with postthrombophlebitic syndrome of the lower extremities. Along with the routine surgical methods of treatment the authors suggested and performed in 30 patients a new operative procedure--communicotomy, that consists in separation of the superficial and profound venous systems in the lower crural third via a separate incision in the upper crural third. To this end a new instrument--a communicotome was devised. Indications to some or other kind of surgery were elaborated by the authors. 76% of patients showed an improvement within the terms from 1 to 6 years postoperatively."} {"id": "PMID:1274114", "title": "[Method of compression arthrodesis of the ankle and foot joints].", "content": "A modified F.R. Bogdanov arthrodesis of the talocrural joint is described. The authors employed an external compression with three Kirschner pins, inserted in the tibial, calcanial and scaphoid bones. Late results of the operation were followed up in 20 patients. A complete correction, osteoankylosis of arthrodesized joints and rehabilitation of the weight-bearing function of the foot and extremity, as a whole, were gained in all patients.", "contents": "[Method of compression arthrodesis of the ankle and foot joints]. A modified F.R. Bogdanov arthrodesis of the talocrural joint is described. The authors employed an external compression with three Kirschner pins, inserted in the tibial, calcanial and scaphoid bones. Late results of the operation were followed up in 20 patients. A complete correction, osteoankylosis of arthrodesized joints and rehabilitation of the weight-bearing function of the foot and extremity, as a whole, were gained in all patients."} {"id": "PMID:1274116", "title": "[Possibilities of prevention of posttraumatic fat embolism].", "content": "Hypocoagulation induced artificially with anticoagulants of an indirect action in patients, subjected to osteotomy of the femoral bone, resulted in diminishing of the intensity of fat globulemia and a decrease in the average size of fat globules, thus lessening the risk of fat embolism.", "contents": "[Possibilities of prevention of posttraumatic fat embolism]. Hypocoagulation induced artificially with anticoagulants of an indirect action in patients, subjected to osteotomy of the femoral bone, resulted in diminishing of the intensity of fat globulemia and a decrease in the average size of fat globules, thus lessening the risk of fat embolism."} {"id": "PMID:1274117", "title": "[Certain characteristics of surgical treatment of fractures of the lateral segment of the pelvic ring].", "content": "The author reports the results of surgical therapy for fractures of the lateral pelvic arch in 19 patients. The technic of metallic osteosynthesis is described. In 17 patients good and satisfactory issues were gained. In 2 cases the displacement of fragments failed to be eliminated in late terms of the operation, and functional results proved to be poor.", "contents": "[Certain characteristics of surgical treatment of fractures of the lateral segment of the pelvic ring]. The author reports the results of surgical therapy for fractures of the lateral pelvic arch in 19 patients. The technic of metallic osteosynthesis is described. In 17 patients good and satisfactory issues were gained. In 2 cases the displacement of fragments failed to be eliminated in late terms of the operation, and functional results proved to be poor."} {"id": "PMID:1274122", "title": "[Acute appendicitis in young children].", "content": "Ninety two children aged up to 3 years and operated upon for acute appendicitis were observed. The clinical picture of appendicitis is described, and some diagnostic difficulties are noted. The mortality due to appendicitis in this group of patients was 15.2%.", "contents": "[Acute appendicitis in young children]. Ninety two children aged up to 3 years and operated upon for acute appendicitis were observed. The clinical picture of appendicitis is described, and some diagnostic difficulties are noted. The mortality due to appendicitis in this group of patients was 15.2%."} {"id": "PMID:1274123", "title": "The unified concept of shock.", "content": "In summary, the shock syndrome has a variety of causes although the same net physiologic insult results. The disease is a deficiency in tissue metabolism brought about by decreased capillary blood flow and cellular hypoxia. The therapeutic regimen employed in any given patient is dectated by the initial cause of shock as well as the physiologic changes that have occurred in the patient. Fluid and electrolyte therapy is the primary method of treatment. Modification of solutions and use of additional drugs may be indicated.", "contents": "The unified concept of shock. In summary, the shock syndrome has a variety of causes although the same net physiologic insult results. The disease is a deficiency in tissue metabolism brought about by decreased capillary blood flow and cellular hypoxia. The therapeutic regimen employed in any given patient is dectated by the initial cause of shock as well as the physiologic changes that have occurred in the patient. Fluid and electrolyte therapy is the primary method of treatment. Modification of solutions and use of additional drugs may be indicated."} {"id": "PMID:1274133", "title": "Veterinary information: the current situation and future trends.", "content": "Veterinary science is well supplied with abstracting and indexing hournals. Both experience and an investigation undertaken for the Food and Agriculture Organisation indicate that they are comprehensive in scope and subject coverage. Computer operation of information services is now routine, and mechanised alerting and retrospective services are available. A veterinary round table was set up in 1973 by the Commission of the European Communities to attempt to improve veterinary information. The round table is conducting a detailed study of the value of the available machine information systems to veterinarians and is compiling a multi-lingual thesaurus. In addition, it is investigating the need for a new review journal, methods of recording animal disease incidence and variations in the needs of the different types of veterinarians for information. The use of machine information systems is expected to become more widespread in the near future. Many will be available on-line, a method of working which offers great advantages in speed and flexibility of operation.", "contents": "Veterinary information: the current situation and future trends. Veterinary science is well supplied with abstracting and indexing hournals. Both experience and an investigation undertaken for the Food and Agriculture Organisation indicate that they are comprehensive in scope and subject coverage. Computer operation of information services is now routine, and mechanised alerting and retrospective services are available. A veterinary round table was set up in 1973 by the Commission of the European Communities to attempt to improve veterinary information. The round table is conducting a detailed study of the value of the available machine information systems to veterinarians and is compiling a multi-lingual thesaurus. In addition, it is investigating the need for a new review journal, methods of recording animal disease incidence and variations in the needs of the different types of veterinarians for information. The use of machine information systems is expected to become more widespread in the near future. Many will be available on-line, a method of working which offers great advantages in speed and flexibility of operation."} {"id": "PMID:1274134", "title": "The prevalence of Gasterophilus intestinalis and G nasalis in horses in Ireland.", "content": "During the months October-May inclusive 90-8% of horses slaughtered at an abattoir near Dublin and 66-9% of those at an abattoir near Belfast were infected with Gasterophilus intestinalis; 28-6% of horses at the former abattoir harboured G nasalis while none of the horses examined at the latter abattoir was found to be infected with this species.", "contents": "The prevalence of Gasterophilus intestinalis and G nasalis in horses in Ireland. During the months October-May inclusive 90-8% of horses slaughtered at an abattoir near Dublin and 66-9% of those at an abattoir near Belfast were infected with Gasterophilus intestinalis; 28-6% of horses at the former abattoir harboured G nasalis while none of the horses examined at the latter abattoir was found to be infected with this species."} {"id": "PMID:1274139", "title": "Chronic renal failure in dogs: a comparative clinical and morphological study of chronic glomerulonephritis and chronic interstitial nephritis.", "content": "Chronic renal disease is an important clinical problem in dogs. Until recently, diffuse renal fibrosis with chronic renal failure has been attributed mainly to chronic interstitial nephritis, itself considered to be the end stage of acute leptospiral nephritis. A clinical and morphological analysis of eight cases of chronic glomerulonephritis is described and a comparison made with eight dogs suffering from severe chronic interstitial nephritis. Clinically and biochemically, the two diseases were virtually indistinguishable, both resulting in uraemia. A possible distinguishing feature of chronic interstitial nephritis was the anaemia which was absent from chronic glomerulonephritis cases. Morphologically, the two diseases appeared to be distinguishable on three grounds; the pattern and severity of fibrosis, the degree of fibrin deposition and the immunofluorescence findings.", "contents": "Chronic renal failure in dogs: a comparative clinical and morphological study of chronic glomerulonephritis and chronic interstitial nephritis. Chronic renal disease is an important clinical problem in dogs. Until recently, diffuse renal fibrosis with chronic renal failure has been attributed mainly to chronic interstitial nephritis, itself considered to be the end stage of acute leptospiral nephritis. A clinical and morphological analysis of eight cases of chronic glomerulonephritis is described and a comparison made with eight dogs suffering from severe chronic interstitial nephritis. Clinically and biochemically, the two diseases were virtually indistinguishable, both resulting in uraemia. A possible distinguishing feature of chronic interstitial nephritis was the anaemia which was absent from chronic glomerulonephritis cases. Morphologically, the two diseases appeared to be distinguishable on three grounds; the pattern and severity of fibrosis, the degree of fibrin deposition and the immunofluorescence findings."} {"id": "PMID:1274140", "title": "Ectopic ureter in the bitch.", "content": "Ectopic ureter in the dog is only sporadically reported. A case in an adult golden retriever is described.", "contents": "Ectopic ureter in the bitch. Ectopic ureter in the dog is only sporadically reported. A case in an adult golden retriever is described."} {"id": "PMID:1274145", "title": "Observations on Isospora suis infection in a minimal disease pig herd.", "content": "Faeces samples from 11 sows and their litters and intestinal contents and scrapings collected from 56 piglets at the time of slaughter were examined for Isospora suis. The findings indicate that oocysts with sporoblasts can be found in faeces samples 24 hours after collection; the prepatent period is about six to nine days and the patent period three to eight days (adjudged under non-experimental conditions); piglets in an infected herd are normally resistant to natural infection for the first three weeks of life. Infection is followed by the development of an active immunity which is not affected by the stress of farrowing.", "contents": "Observations on Isospora suis infection in a minimal disease pig herd. Faeces samples from 11 sows and their litters and intestinal contents and scrapings collected from 56 piglets at the time of slaughter were examined for Isospora suis. The findings indicate that oocysts with sporoblasts can be found in faeces samples 24 hours after collection; the prepatent period is about six to nine days and the patent period three to eight days (adjudged under non-experimental conditions); piglets in an infected herd are normally resistant to natural infection for the first three weeks of life. Infection is followed by the development of an active immunity which is not affected by the stress of farrowing."} {"id": "PMID:1274258", "title": "[Angioscanning in the diagnosis of tumors of the soft tissues of the extremities].", "content": "The results of radioisotope scanning in 70 patients with tumors and nontumor lesions of soft tissues of the extremities are presented. It was found that angioscanning with macroalbumin-iodine-131 (MAA-J-131) allows visualization of malignant tumors of soft tissues.", "contents": "[Angioscanning in the diagnosis of tumors of the soft tissues of the extremities]. The results of radioisotope scanning in 70 patients with tumors and nontumor lesions of soft tissues of the extremities are presented. It was found that angioscanning with macroalbumin-iodine-131 (MAA-J-131) allows visualization of malignant tumors of soft tissues."} {"id": "PMID:1274259", "title": "[External respiration in radiation treatment of patients with breast cancer].", "content": "The data on the ventilatory status in 119 patients subjected to combined therapy are reported. Roentgenodynamic investigation of the ventilation indicated changes in the mechanism of the latter on account of a limitation of the ventilatory function of muscle realizing inhalation. Ventilatory disturbances induced by irradiation of the chest are accompanied with functional compensation. Normal gas metabolism is provided by hyperfunction of the lung and respiratory muscles on the intact side.", "contents": "[External respiration in radiation treatment of patients with breast cancer]. The data on the ventilatory status in 119 patients subjected to combined therapy are reported. Roentgenodynamic investigation of the ventilation indicated changes in the mechanism of the latter on account of a limitation of the ventilatory function of muscle realizing inhalation. Ventilatory disturbances induced by irradiation of the chest are accompanied with functional compensation. Normal gas metabolism is provided by hyperfunction of the lung and respiratory muscles on the intact side."} {"id": "PMID:1274260", "title": "[Diagnostic laparotomy in patients with lymphogranulomatosis].", "content": "The authors' experience with 80 diagnostic laparotomies with the removal of the spleen, performed in patients showing lymphogranulomatosis, is summarized. As a result of surgery in 40 patients the stage of the diseases was revised and therapeutic policy was altered, that is felt to warrant the risk of surgical intervention.", "contents": "[Diagnostic laparotomy in patients with lymphogranulomatosis]. The authors' experience with 80 diagnostic laparotomies with the removal of the spleen, performed in patients showing lymphogranulomatosis, is summarized. As a result of surgery in 40 patients the stage of the diseases was revised and therapeutic policy was altered, that is felt to warrant the risk of surgical intervention."} {"id": "PMID:1274262", "title": "[Differentiation of tumors of the anterior wall of the stomach from neighboring intact areas by the method of multichannel gastrography].", "content": "By means of simultaneous multichannel recording of stomach biopotentials from the surface of the anterial abdominal wall, an active electrode being situated above tumor, we are able to recognize the decreased electric activity of the anterior gastric wall area, involved by cancer process. Multichannel electrogastrography from the body surface makes it possible to determine the boundary between the tumor and adjacent intact areas of the anterior gastric wall clearly enough.", "contents": "[Differentiation of tumors of the anterior wall of the stomach from neighboring intact areas by the method of multichannel gastrography]. By means of simultaneous multichannel recording of stomach biopotentials from the surface of the anterial abdominal wall, an active electrode being situated above tumor, we are able to recognize the decreased electric activity of the anterior gastric wall area, involved by cancer process. Multichannel electrogastrography from the body surface makes it possible to determine the boundary between the tumor and adjacent intact areas of the anterior gastric wall clearly enough."} {"id": "PMID:1274263", "title": "[Limits of the spread of cancer of the rectum (morphological study)].", "content": "Fifty five postoperative preparations were studied morphologically after radical surgery for rectal cancer. The distal intramural spread of adenocarcinoma was noted in 18.5 per cent. Orthograde lymphnodes were involved in 43.1%, retrograde ones - in 18%. The tumor growth in perirectal cellular tissue was manifested mainly in the area of the principal tumor. The safe level of rectum cutting is 4.5cm down the tumor. It is recommended to take into a careful consideration the limits of intra- and extramural spread of tumor for the performance of sphincter-preserving operations.", "contents": "[Limits of the spread of cancer of the rectum (morphological study)]. Fifty five postoperative preparations were studied morphologically after radical surgery for rectal cancer. The distal intramural spread of adenocarcinoma was noted in 18.5 per cent. Orthograde lymphnodes were involved in 43.1%, retrograde ones - in 18%. The tumor growth in perirectal cellular tissue was manifested mainly in the area of the principal tumor. The safe level of rectum cutting is 4.5cm down the tumor. It is recommended to take into a careful consideration the limits of intra- and extramural spread of tumor for the performance of sphincter-preserving operations."} {"id": "PMID:1274264", "title": "[Mitotic cycle in cell cultures infected with oncogenic type-12 adenoviruses].", "content": "Oncogenic adenovirus of type 12 in the culture of rat embryo fibroblasts, in which it induces an abortive infection, and in HEp-2 culture, whereas it shows reproduction and causes lytic infection, in the early stationary phase causes shortening of the mitotic cycle and its separate periods. Reduction of the mitotic cycle duration occurs on account of shortening of the presynthetic stage and DNA synthesis stage. This property of the virus is in agreement with its capacity to stimulate proliferation of infected cells and is likely to be one of the necessary conditions for development of malignant transformation.", "contents": "[Mitotic cycle in cell cultures infected with oncogenic type-12 adenoviruses]. Oncogenic adenovirus of type 12 in the culture of rat embryo fibroblasts, in which it induces an abortive infection, and in HEp-2 culture, whereas it shows reproduction and causes lytic infection, in the early stationary phase causes shortening of the mitotic cycle and its separate periods. Reduction of the mitotic cycle duration occurs on account of shortening of the presynthetic stage and DNA synthesis stage. This property of the virus is in agreement with its capacity to stimulate proliferation of infected cells and is likely to be one of the necessary conditions for development of malignant transformation."} {"id": "PMID:1274265", "title": "[Acetylation reaction in mice in the normal state and in tumors].", "content": "Studies of peculiarities of acetylation with the use of sulfadimidine showed the distribution of female white non-bred mice into two groups - with high and low activity. In C3H/He mice a relatively high activity of sulfadimidine acetylation was observed, while in C57BL/He mice a low activity of acetylation was noted. The growth of transplanted melanoma B-16 in C57BL/He mice and sarcoma 37 and sarcoma 180 in non-bred mice resulted in an increased activity of sulfadimidine acetylation. The use of w-sodium methylpantothenate (an antagonist of pantothenic acid) failed to show an increased activity of sulfadimidine acetylation and inhibited the tumor growth.", "contents": "[Acetylation reaction in mice in the normal state and in tumors]. Studies of peculiarities of acetylation with the use of sulfadimidine showed the distribution of female white non-bred mice into two groups - with high and low activity. In C3H/He mice a relatively high activity of sulfadimidine acetylation was observed, while in C57BL/He mice a low activity of acetylation was noted. The growth of transplanted melanoma B-16 in C57BL/He mice and sarcoma 37 and sarcoma 180 in non-bred mice resulted in an increased activity of sulfadimidine acetylation. The use of w-sodium methylpantothenate (an antagonist of pantothenic acid) failed to show an increased activity of sulfadimidine acetylation and inhibited the tumor growth."} {"id": "PMID:1274266", "title": "[Mechanism of the induction of asbestos mesotheliomas in the pleura of rats].", "content": "The first group of non-bred rats was injected intrapleurally 20 mg of benzene extracted chrysotil-asbestos dust in saline; the second group of rats was injected 20 mg of the same dust but with benz(a)pyrene absorbed on it (0.4 mg). Pleural mesotheliomas were observed in 48.57% of cases in the first group and in 41.37% of cases in the second one. The difference was not significant. There was no difference in the percentage of premesotheliomatous lesions. But, in the second group tumors of other organs were found. The role of asbestos pollution by carcinogenic hydrocarbons in the genesis of lung cancer and pleural mesothelioma is discussed.", "contents": "[Mechanism of the induction of asbestos mesotheliomas in the pleura of rats]. The first group of non-bred rats was injected intrapleurally 20 mg of benzene extracted chrysotil-asbestos dust in saline; the second group of rats was injected 20 mg of the same dust but with benz(a)pyrene absorbed on it (0.4 mg). Pleural mesotheliomas were observed in 48.57% of cases in the first group and in 41.37% of cases in the second one. The difference was not significant. There was no difference in the percentage of premesotheliomatous lesions. But, in the second group tumors of other organs were found. The role of asbestos pollution by carcinogenic hydrocarbons in the genesis of lung cancer and pleural mesothelioma is discussed."} {"id": "PMID:1274267", "title": "[Influence of diazan on the mitotic cycle of leukemia L1210 cells].", "content": "By means of a autoradiographic method the effect of diazane - a new antitumor substance from the diasoketones class, on the mitotic cycle of leucimia L 1210 has been studied. Diazane in single administration was found to inhibit the development of leucemic process during 2 days. This substance reduces considerably the DNA synthesis intensity in cells, due to that the mitotic activity of cells is markedly reduced. It was demonstrated that diazane during 8 hours blocked the transfer of cells from a presynthetic stage into the DNA synthesis phase. But this substance does not influence the transfer of cells from the premitotic period into mitosis. The substance delayes continuously (during 36 hours) the division of cells being in a phase of the DNA synthesis during its injection. In later terms although multiplication of these cells would be restored, but its intensity is decreased.", "contents": "[Influence of diazan on the mitotic cycle of leukemia L1210 cells]. By means of a autoradiographic method the effect of diazane - a new antitumor substance from the diasoketones class, on the mitotic cycle of leucimia L 1210 has been studied. Diazane in single administration was found to inhibit the development of leucemic process during 2 days. This substance reduces considerably the DNA synthesis intensity in cells, due to that the mitotic activity of cells is markedly reduced. It was demonstrated that diazane during 8 hours blocked the transfer of cells from a presynthetic stage into the DNA synthesis phase. But this substance does not influence the transfer of cells from the premitotic period into mitosis. The substance delayes continuously (during 36 hours) the division of cells being in a phase of the DNA synthesis during its injection. In later terms although multiplication of these cells would be restored, but its intensity is decreased."} {"id": "PMID:1274268", "title": "[Distribution of ftorafur in the organism of experimental animals].", "content": "Intravenous injection of phtoafur in experimental animals induced the appearance of the biologically active substance in the organism. The concentration of the active substance in blood and organs, reaching its maximum during the first hour, was retained for a long time: an appreciable fall in the substance levels was noted only 12 hours following its injection. In blood and organs of animals with a sensitive tumor levels of the active substance are considerably lower than in intact animals. This seems to condition the therapeutic effect of the drug.", "contents": "[Distribution of ftorafur in the organism of experimental animals]. Intravenous injection of phtoafur in experimental animals induced the appearance of the biologically active substance in the organism. The concentration of the active substance in blood and organs, reaching its maximum during the first hour, was retained for a long time: an appreciable fall in the substance levels was noted only 12 hours following its injection. In blood and organs of animals with a sensitive tumor levels of the active substance are considerably lower than in intact animals. This seems to condition the therapeutic effect of the drug."} {"id": "PMID:1274269", "title": "[Survival of patients with inoperable stomach cancer treated with 5-fluorouracil].", "content": "Late results of treatment in 71 patients are analysed. The survival during 2 years following tentative laparotomy in 35 patients, treated with 5-fluoruracil with a clinical effect (objective and symptomatic improvement), was reliably higher than the survival of patients treated without any effect. The comparable groups of patients did not differ in the extent of tumor spread, however, in patients treated with the effect the time elapsed since tentative laparotomy up to the initiation of chemotherapy was reliably longer than in those treated without any effect. It is assumed that the duration of this period is an indirect index reflecting the rate of tumor growth in different patients. With this in mind, it is suggested that the longer survival of patients, treated with 5-fluoruracil with the effect, may be related with a more favourable course ofthe tumor process in these patients, as compared with those treated without any effect.", "contents": "[Survival of patients with inoperable stomach cancer treated with 5-fluorouracil]. Late results of treatment in 71 patients are analysed. The survival during 2 years following tentative laparotomy in 35 patients, treated with 5-fluoruracil with a clinical effect (objective and symptomatic improvement), was reliably higher than the survival of patients treated without any effect. The comparable groups of patients did not differ in the extent of tumor spread, however, in patients treated with the effect the time elapsed since tentative laparotomy up to the initiation of chemotherapy was reliably longer than in those treated without any effect. It is assumed that the duration of this period is an indirect index reflecting the rate of tumor growth in different patients. With this in mind, it is suggested that the longer survival of patients, treated with 5-fluoruracil with the effect, may be related with a more favourable course ofthe tumor process in these patients, as compared with those treated without any effect."} {"id": "PMID:1274270", "title": "[Experience in the diagnosis and treatment of cancer of the rectum].", "content": "The results of diagnosis and treatment of rectal cancer in 92 patients are analysed. Four clinical forms of rectal cancer were differentiated: with predominant local signs, with predominant general symptoms, with an asymptomatic course and with signs of functional disorders in pelvic organs. In these cases dyselectrolitemia, manifested in hyponatriemia, hypokaliemia and hypochloremia, was noted. According to phase analysis data of the cardiac activity in these patients the myocardial contractility is diminished. Abdomino-anal resection of the obturatory apparatus of the sigmoid is felt to be the operation of choice in rectal cancer, if permitted by tumor localization, its size and anatomical features of the sigmoid.", "contents": "[Experience in the diagnosis and treatment of cancer of the rectum]. The results of diagnosis and treatment of rectal cancer in 92 patients are analysed. Four clinical forms of rectal cancer were differentiated: with predominant local signs, with predominant general symptoms, with an asymptomatic course and with signs of functional disorders in pelvic organs. In these cases dyselectrolitemia, manifested in hyponatriemia, hypokaliemia and hypochloremia, was noted. According to phase analysis data of the cardiac activity in these patients the myocardial contractility is diminished. Abdomino-anal resection of the obturatory apparatus of the sigmoid is felt to be the operation of choice in rectal cancer, if permitted by tumor localization, its size and anatomical features of the sigmoid."} {"id": "PMID:1274272", "title": "[Cancer of the rectum (according to data of the Rovno District Oncological Dispensary)].", "content": "The results of diagnosis and treatment of 255 patients with rectal cancer, treated in Rovno Province dispensary since 1950 to 1974, are analysed. A 5-year survival made nearly 50% and was dependent on the stage of the disease.", "contents": "[Cancer of the rectum (according to data of the Rovno District Oncological Dispensary)]. The results of diagnosis and treatment of 255 patients with rectal cancer, treated in Rovno Province dispensary since 1950 to 1974, are analysed. A 5-year survival made nearly 50% and was dependent on the stage of the disease."} {"id": "PMID:1274273", "title": "[Experience in the treatment of early forms of cancer of the cervix uteri].", "content": "The results of treatment of 378 patients with early forms of cervical cancer are presented. In 185 patients with intraepithelial cancer electroexcision and common extirpation of the uterus was employed, and in 193 patients with early invasive cancer different therapy was used: surgical (routine and extensive hysterectomy), combined and associated radiotherapy. The terms of observation for 3, 5 and 10 years indicated a cure in 97.1% of patients with intraepithelial cancer and in 98.4% of patients with early invasive cancer of the uterine cervix.", "contents": "[Experience in the treatment of early forms of cancer of the cervix uteri]. The results of treatment of 378 patients with early forms of cervical cancer are presented. In 185 patients with intraepithelial cancer electroexcision and common extirpation of the uterus was employed, and in 193 patients with early invasive cancer different therapy was used: surgical (routine and extensive hysterectomy), combined and associated radiotherapy. The terms of observation for 3, 5 and 10 years indicated a cure in 97.1% of patients with intraepithelial cancer and in 98.4% of patients with early invasive cancer of the uterine cervix."} {"id": "PMID:1274275", "title": "[Endolymphatic infusions in oncological patients].", "content": "Utilization of endolymphatic infusions against the background of the impaired barrier function of lymph nodes is inherent in a higher rate of tumor metastasization. The hazard increases in cases when tumore cells in the lymph system (especially in the thoracic duct) are in a free state, and substances dilating lymph vessels are employed. Therefore, endolymphatic infusions should be accomplished taking into account all the factors that could lower either directly or indirectly the barrier function of the lymphatic system.", "contents": "[Endolymphatic infusions in oncological patients]. Utilization of endolymphatic infusions against the background of the impaired barrier function of lymph nodes is inherent in a higher rate of tumor metastasization. The hazard increases in cases when tumore cells in the lymph system (especially in the thoracic duct) are in a free state, and substances dilating lymph vessels are employed. Therefore, endolymphatic infusions should be accomplished taking into account all the factors that could lower either directly or indirectly the barrier function of the lymphatic system."} {"id": "PMID:1274277", "title": "[Role of genealogical studies for the prevention of malignant neoplasms].", "content": "Based on clinico-genealogical studies of 219 cancer patients, whose relatives suffered neoplastic processes, it was concluded that a hereditory factor plays a definite role in cancer morbidity. It seems to be rational to single out the relatives of the proband as a high-risk group in malignant tumor morbidity and to keep them under a dispensary control.", "contents": "[Role of genealogical studies for the prevention of malignant neoplasms]. Based on clinico-genealogical studies of 219 cancer patients, whose relatives suffered neoplastic processes, it was concluded that a hereditory factor plays a definite role in cancer morbidity. It seems to be rational to single out the relatives of the proband as a high-risk group in malignant tumor morbidity and to keep them under a dispensary control."} {"id": "PMID:1274280", "title": "[Problem of classifying malignant lymphomas].", "content": "The classification of malignant lymphomas (ML) after Rappaport is characterized by precise criteria and contributes to a mutual understanding of morphologists and clinicians. The detection of a nonspecific esterase activity facilitates the identification of ML cell elements, since the enzyme activity is insignificant in lymphocytes and intensive in histiocytes. Moreover, the method facilitates to diagnose nodular forms of ML since it aids in revealing the compression of lymph node stroma with tumor foci.", "contents": "[Problem of classifying malignant lymphomas]. The classification of malignant lymphomas (ML) after Rappaport is characterized by precise criteria and contributes to a mutual understanding of morphologists and clinicians. The detection of a nonspecific esterase activity facilitates the identification of ML cell elements, since the enzyme activity is insignificant in lymphocytes and intensive in histiocytes. Moreover, the method facilitates to diagnose nodular forms of ML since it aids in revealing the compression of lymph node stroma with tumor foci."} {"id": "PMID:1274281", "title": "[Prospects for sanatorium-health resort treatment of oncological patients].", "content": "The current opinion that oncological patients subjected to radical treatment are not allowed to be directed to sanatoriums and resorts should be revised. It is necessary to plan joint investigations of oncologists and specialists or resort cure to determine exactly indications and contraindications to subsequent cure of such patients under sanatorium conditions in early terms after cessation of radical therapy. Patients, previously treated for malignant tumors and showing no signs of recurrence or metastases, may be directed to appropriate sanatoriums for treatment of concomitant lesions, but without applying mudtherapy, ultraviolet irradiation and general heat procedures.", "contents": "[Prospects for sanatorium-health resort treatment of oncological patients]. The current opinion that oncological patients subjected to radical treatment are not allowed to be directed to sanatoriums and resorts should be revised. It is necessary to plan joint investigations of oncologists and specialists or resort cure to determine exactly indications and contraindications to subsequent cure of such patients under sanatorium conditions in early terms after cessation of radical therapy. Patients, previously treated for malignant tumors and showing no signs of recurrence or metastases, may be directed to appropriate sanatoriums for treatment of concomitant lesions, but without applying mudtherapy, ultraviolet irradiation and general heat procedures."} {"id": "PMID:1274282", "title": "[Role of the hypothalamus in the formation of antitumor resistance].", "content": "The development of Brown-Pearce tumor in rabbits is accompanied with regular changes in the functional activity of the hypothalamic zone, related close enough with the regulation of adrenal cortex functions and immunological processes. In electrostimulation of the posterior hypothalamus median zones an accelerated resorption of the tumor, inoculated subcutaneously, was noted. The destruction of the posteromedian hypothalamic structures resulted in a sharp fall of corticosteroids level in the organism and a decreased intensity of generally persistant immunity to repeat inoculations of Brown-Pearce tumor. Thus, the fact of the immunocompetent system being ready to realize protective reactions for preservation of the genetic constancy of the organism is conditioned by the hypothalamo-hypophyseal-adrenal system functional activity.", "contents": "[Role of the hypothalamus in the formation of antitumor resistance]. The development of Brown-Pearce tumor in rabbits is accompanied with regular changes in the functional activity of the hypothalamic zone, related close enough with the regulation of adrenal cortex functions and immunological processes. In electrostimulation of the posterior hypothalamus median zones an accelerated resorption of the tumor, inoculated subcutaneously, was noted. The destruction of the posteromedian hypothalamic structures resulted in a sharp fall of corticosteroids level in the organism and a decreased intensity of generally persistant immunity to repeat inoculations of Brown-Pearce tumor. Thus, the fact of the immunocompetent system being ready to realize protective reactions for preservation of the genetic constancy of the organism is conditioned by the hypothalamo-hypophyseal-adrenal system functional activity."} {"id": "PMID:1274283", "title": "[Transcortin binding capacity in the blood plasma of rats with a growing sarcoma 45].", "content": "It was shown that at the 10th day of sarcoma 45 growth the content of transcortine bound and free 11-oxycorticosteroids (11-OCS) in plasma of rat peripheral blood was increased. At the 30th day of the tumor growth the content of total and protein bound 11-OCS was decreased, accordingly by 57 and 61%. Following single hydrocortisone injections in intact rats and rats with sarcoma 45, on the 10th day of its growth, a marked increase in the content of bound 11-OCS was noted, as compared with animals receiving saline solution. On the 20-30th day of the tumor growth such effect was not observed. On the 20-30th day of sarcoma 45 growth 8-9% of the value of exogenic hydrocortisone, bound to blood plasma transcortins in intact rats, were found to be tracortin bound.", "contents": "[Transcortin binding capacity in the blood plasma of rats with a growing sarcoma 45]. It was shown that at the 10th day of sarcoma 45 growth the content of transcortine bound and free 11-oxycorticosteroids (11-OCS) in plasma of rat peripheral blood was increased. At the 30th day of the tumor growth the content of total and protein bound 11-OCS was decreased, accordingly by 57 and 61%. Following single hydrocortisone injections in intact rats and rats with sarcoma 45, on the 10th day of its growth, a marked increase in the content of bound 11-OCS was noted, as compared with animals receiving saline solution. On the 20-30th day of the tumor growth such effect was not observed. On the 20-30th day of sarcoma 45 growth 8-9% of the value of exogenic hydrocortisone, bound to blood plasma transcortins in intact rats, were found to be tracortin bound."} {"id": "PMID:1274286", "title": "Storage of human platelets by freezing.", "content": "Prolonged, probably indefinite storage of viable and functional human platelets is now possible by freezing with dimethylsulfoxide (DMSO). These platelets have a nearly normal survival upon reinfusion and are capable of sustained hemostatic effectiveness in thrombocytopenic patients. Adaptation of the freezing technique for large-scale usage has more recently been achieved. The method is mainly based on the following principles: (1) use of plasma for suspension of the platelet concentrate; (2) gradual addition (0.5% every 2 min) of DMSO to a final concentration of 5% and its gradual removal; (3) a slow cooling rate of about 1 degree C per min and rapid thawing (in 1 min); (4) use of a polyolefin plastic bag for freezing; (5) a washing medium of 20% plasma in Hanks' balanced salt solution; (6) final resuspension of the platelets in 50% plasma in Hanks' solution.", "contents": "Storage of human platelets by freezing. Prolonged, probably indefinite storage of viable and functional human platelets is now possible by freezing with dimethylsulfoxide (DMSO). These platelets have a nearly normal survival upon reinfusion and are capable of sustained hemostatic effectiveness in thrombocytopenic patients. Adaptation of the freezing technique for large-scale usage has more recently been achieved. The method is mainly based on the following principles: (1) use of plasma for suspension of the platelet concentrate; (2) gradual addition (0.5% every 2 min) of DMSO to a final concentration of 5% and its gradual removal; (3) a slow cooling rate of about 1 degree C per min and rapid thawing (in 1 min); (4) use of a polyolefin plastic bag for freezing; (5) a washing medium of 20% plasma in Hanks' balanced salt solution; (6) final resuspension of the platelets in 50% plasma in Hanks' solution."} {"id": "PMID:1274287", "title": "Direct observation of immunoglobulins on the erythrocyte membrane.", "content": "A modification of the sublimation procedure for observation of cell membrane exteriors is described. By retaining basic advantages of the freeze-fracture technique, without actual fracturing of the sample, high quality replicas can be produced on which molecules such as immunoglobulins can be identified and mapped on extensive areas of the erythrocyte membrane surfaces. The method can be used for direct observation of antibodies without recourse to labelling with other marker molecules, such as for example ferritin. In addition, direct visualization of clumping of red cells, as induced by such antibodies, is feasible.", "contents": "Direct observation of immunoglobulins on the erythrocyte membrane. A modification of the sublimation procedure for observation of cell membrane exteriors is described. By retaining basic advantages of the freeze-fracture technique, without actual fracturing of the sample, high quality replicas can be produced on which molecules such as immunoglobulins can be identified and mapped on extensive areas of the erythrocyte membrane surfaces. The method can be used for direct observation of antibodies without recourse to labelling with other marker molecules, such as for example ferritin. In addition, direct visualization of clumping of red cells, as induced by such antibodies, is feasible."} {"id": "PMID:1274288", "title": "Characterisation of autoantibodies to erythrocytes in autoimmune haemolytic anaemia by chloroquine.", "content": "Chloroquine splits autoantibodies from erythrocytes of patients with autoimmune haemolytic anaemia in vitro. After the removal of chloroquine from the samples the autoantibodies can be identified in the eluates. With one exception the autoantibodies of patients with idiopathic autoimmune haemolytic anaemia (AIHA) and severe haemolysis were completely split from the cells, whereas the autoantibodies of patients with symptomatic AIHA and moderate anaemia, of patients with diseases unrelated to haemolysis, and of healthy persons, were not completely split from the erythrocytes. In general, autoantibodies, which are associated with severe haemolysis, were more easily split from the red cells by chloroquine. The eluted IgG incomplete warm autoantibodies were only in part specific to Rh antigens. The Rh specificity does not correlate with the absence of presence of increased haemolysis. The inhibition of the autoantibodies and the splitting or 'loosening' of the antigen-antibody linkage with the immunocomplex by chloroquine could be responsible of a longer survival of autoantibody-coated red cells in patients with AIHA.", "contents": "Characterisation of autoantibodies to erythrocytes in autoimmune haemolytic anaemia by chloroquine. Chloroquine splits autoantibodies from erythrocytes of patients with autoimmune haemolytic anaemia in vitro. After the removal of chloroquine from the samples the autoantibodies can be identified in the eluates. With one exception the autoantibodies of patients with idiopathic autoimmune haemolytic anaemia (AIHA) and severe haemolysis were completely split from the cells, whereas the autoantibodies of patients with symptomatic AIHA and moderate anaemia, of patients with diseases unrelated to haemolysis, and of healthy persons, were not completely split from the erythrocytes. In general, autoantibodies, which are associated with severe haemolysis, were more easily split from the red cells by chloroquine. The eluted IgG incomplete warm autoantibodies were only in part specific to Rh antigens. The Rh specificity does not correlate with the absence of presence of increased haemolysis. The inhibition of the autoantibodies and the splitting or 'loosening' of the antigen-antibody linkage with the immunocomplex by chloroquine could be responsible of a longer survival of autoantibody-coated red cells in patients with AIHA."} {"id": "PMID:1274335", "title": "Percutaneous radiofrequency trigeminal gangliolysis in the treatment of tic douloureux.", "content": "The treatment of tic douloureux was dramatically altered in 1962 with the demonstration that carbamazepine (Tegretol(R)) alone or in combination with diphenylhydantoin sodium (Dilantin(R)) was effective in controlling the painful paroxysms. However, 30 percent of the patients so treated have not been successfully managed and some type of surgical therapy is required to control their pain. A wide variety of surgical alternatives are available but they all trade a sensory deficit for pain relief and have a significant risk of morbidity and mortality. Experience with percutaneous radiofrequency trigeminal gangliolysis has indicated that this new technique is capable of producing lasting relief of tic douloureux in as many as 95 percent of the patients. To date there have been no deaths from this procedure and a very low incidence of minor complications. It achieves this high success rate at the expense of only partial sensory deficits restricted to a circumscribed area of the face. No other surgical alternative carries such a high long-term success rate with a low complication rate. We believe that percutaneous radiofrequency trigeminal gangliolysis has become the surgical treatment of choice for tic douloureux.", "contents": "Percutaneous radiofrequency trigeminal gangliolysis in the treatment of tic douloureux. The treatment of tic douloureux was dramatically altered in 1962 with the demonstration that carbamazepine (Tegretol(R)) alone or in combination with diphenylhydantoin sodium (Dilantin(R)) was effective in controlling the painful paroxysms. However, 30 percent of the patients so treated have not been successfully managed and some type of surgical therapy is required to control their pain. A wide variety of surgical alternatives are available but they all trade a sensory deficit for pain relief and have a significant risk of morbidity and mortality. Experience with percutaneous radiofrequency trigeminal gangliolysis has indicated that this new technique is capable of producing lasting relief of tic douloureux in as many as 95 percent of the patients. To date there have been no deaths from this procedure and a very low incidence of minor complications. It achieves this high success rate at the expense of only partial sensory deficits restricted to a circumscribed area of the face. No other surgical alternative carries such a high long-term success rate with a low complication rate. We believe that percutaneous radiofrequency trigeminal gangliolysis has become the surgical treatment of choice for tic douloureux."} {"id": "PMID:1274336", "title": "Airborne bacterial contamination of operative wounds.", "content": "Both the numbers and species of airborne bacteria were studied during 263 surgical procedures. The numbers of bacteria isolated were reduced by 95 percent in a horizontal laminar flow room compared with a conventional room and a further 4 percent reduction occurred when a suction-mask system was used. The species of bacteria isolated differed notably at the operative site where a slit sampler was used, as compared with the instrument table and the periphery of the room where settling plates were used. Studies done during simulated surgical operation suggested that light fixtures, pass-through doors, floor contamination and the draped patient were not important sources of airborne contamination in this horizontal laminar flow system. The exact role of airborne bacterial contamination of operative wounds in the development of clinical wound infections is still unknown. Therefore, installation of laminar flow systems must be considered unnecessary at this time.", "contents": "Airborne bacterial contamination of operative wounds. Both the numbers and species of airborne bacteria were studied during 263 surgical procedures. The numbers of bacteria isolated were reduced by 95 percent in a horizontal laminar flow room compared with a conventional room and a further 4 percent reduction occurred when a suction-mask system was used. The species of bacteria isolated differed notably at the operative site where a slit sampler was used, as compared with the instrument table and the periphery of the room where settling plates were used. Studies done during simulated surgical operation suggested that light fixtures, pass-through doors, floor contamination and the draped patient were not important sources of airborne contamination in this horizontal laminar flow system. The exact role of airborne bacterial contamination of operative wounds in the development of clinical wound infections is still unknown. Therefore, installation of laminar flow systems must be considered unnecessary at this time."} {"id": "PMID:1274337", "title": "Prenatal diagnosis and genetic counseling.", "content": "Since the early 1960's knowledge regarding human genetics has increased at an exponential rate. Because genetics was not commonly taught in medical schools before the late 1960's, this review article is intended to acquaint physicians or refresh their knowledge regarding chromosomal, mendelian and multifactorial inheritance and the indications for prenatal diagnosis. Establishing an accurate diagnosis and mode of inheritance is essential in identifying and selecting those families at risk for genetic disease in their offspring. Medical genetics is evolving as a specialty in order to provide consultation and, if needed, management of those families who would benefit by genetic services. Families who would benefit from genetic counseling include, for example, those in whom any of the following conditions is present: known chromosomal disorders, known disorders due to mendelian inheritance, mental retardation of unknown origin, failure of sexual maturation or failure of sexual development, congenital malformations, floppy infant syndrome or leukemia.A list of more than 70 disorders now detectable in a fetus by means of amniocentesis provides a beginning in the prevention of genetic disease. Knowledge regarding these diseases allows a physician to provide families with accurate risk figures so that they may make informed decisions about having children. Also, a compassionate and nonjudgmental approach to counseling is essential. Decisions, in the final analysis, must be made by the family but aided and supported by the physician.", "contents": "Prenatal diagnosis and genetic counseling. Since the early 1960's knowledge regarding human genetics has increased at an exponential rate. Because genetics was not commonly taught in medical schools before the late 1960's, this review article is intended to acquaint physicians or refresh their knowledge regarding chromosomal, mendelian and multifactorial inheritance and the indications for prenatal diagnosis. Establishing an accurate diagnosis and mode of inheritance is essential in identifying and selecting those families at risk for genetic disease in their offspring. Medical genetics is evolving as a specialty in order to provide consultation and, if needed, management of those families who would benefit by genetic services. Families who would benefit from genetic counseling include, for example, those in whom any of the following conditions is present: known chromosomal disorders, known disorders due to mendelian inheritance, mental retardation of unknown origin, failure of sexual maturation or failure of sexual development, congenital malformations, floppy infant syndrome or leukemia.A list of more than 70 disorders now detectable in a fetus by means of amniocentesis provides a beginning in the prevention of genetic disease. Knowledge regarding these diseases allows a physician to provide families with accurate risk figures so that they may make informed decisions about having children. Also, a compassionate and nonjudgmental approach to counseling is essential. Decisions, in the final analysis, must be made by the family but aided and supported by the physician."} {"id": "PMID:1274366", "title": "Excretion of phenol red and its glucuronide in the dogfish shark.", "content": "1. The biliary and urinary excretion of phenol red and its glucuronide was measured in dogfish sharks, Squalus acanthias, in both intact animals and animals with biliary fistula. 2. Phenol red is extensively metabolized to its glucuronide by the dogfish shark and both forms of the compound are actively transported into bile and urine. 3. Both compounds are transferred from plasma to urine and bile against a large concentration gradient; the transfer process is saturable most easily in the renal compartment but also in the hepatic compartment; and both excretion routes for the free drug and the glucuronide are inhibited by probenecid. 4. There were no significant differences in the 48 h biliary excretion of total (free + glucuronide) phenol red, but the urine or intact fish contained two-fold more total drug than did animals with fistulae.", "contents": "Excretion of phenol red and its glucuronide in the dogfish shark. 1. The biliary and urinary excretion of phenol red and its glucuronide was measured in dogfish sharks, Squalus acanthias, in both intact animals and animals with biliary fistula. 2. Phenol red is extensively metabolized to its glucuronide by the dogfish shark and both forms of the compound are actively transported into bile and urine. 3. Both compounds are transferred from plasma to urine and bile against a large concentration gradient; the transfer process is saturable most easily in the renal compartment but also in the hepatic compartment; and both excretion routes for the free drug and the glucuronide are inhibited by probenecid. 4. There were no significant differences in the 48 h biliary excretion of total (free + glucuronide) phenol red, but the urine or intact fish contained two-fold more total drug than did animals with fistulae."} {"id": "PMID:1274367", "title": "Metabolism of 14C-DDT in the mouse and hamster.", "content": "1. When 1,1-bis(p-chloro(14C)phenyl)-2,2,2,-trichloroethane (DDT) was fed to CF-1 mice and Syrian golden hamsters, conjugates of bis(p-chlorophenyl)-acetic acid (DDA) were the major urinary metabolites. As well as DDA-glycine, DDA-alanine and DDA-glucuronic acid previously identified, a new conjugate with serine is reported. 2. Small amounts of non-polar metabolites were detected in urine. Mouse urine contained DDE, whereas this was never detected in hamster urine. The relevance of this finding to the tumorigenicity of DDT in mice, compared with its inactivity in this respect in hamsters, is discussed.", "contents": "Metabolism of 14C-DDT in the mouse and hamster. 1. When 1,1-bis(p-chloro(14C)phenyl)-2,2,2,-trichloroethane (DDT) was fed to CF-1 mice and Syrian golden hamsters, conjugates of bis(p-chlorophenyl)-acetic acid (DDA) were the major urinary metabolites. As well as DDA-glycine, DDA-alanine and DDA-glucuronic acid previously identified, a new conjugate with serine is reported. 2. Small amounts of non-polar metabolites were detected in urine. Mouse urine contained DDE, whereas this was never detected in hamster urine. The relevance of this finding to the tumorigenicity of DDT in mice, compared with its inactivity in this respect in hamsters, is discussed."} {"id": "PMID:1274368", "title": "Effects of insecticide synergists on microsomal oxidation of estradiol and ethynylestradiol and on microsomal drug metabolism.", "content": "1. Oxidation of estradiol and ethynylestradiol at ring A and ring B by rat liver microsomes and NADPH-regenerating system in vitro is inhibited by the two arylimidazole insecticide synergists, 3-bromophenyl-4(5)-imidazole and 1-naphthyl-4(5)-imidazole, but not by the benzothiadiazole insectide synergists 6-nitro-1,2,3-benzothiadiazole and 5,6-dimethyl-1,2,3-benzothiadiazole. The Ki of the most potent inhibitor, 1-naphthyl-4(5)-imidazole, was 3 X 10(-6) M. 2. 6-Nitro-1,2,3-benzothiadiazole (10(-6) M), which did not inhibit hydroxylation of the estrogens, inhibited oxidation of aniline and demethylation of ethylmorphine, p-nitroanisole, and aminopyrine by 30-70%. 5,6-Dimethyl-1,2,3-benzothiadiazole inhibited only demethylation of p-nitroanisole and aminopyrine. From these results the presence of different hepatic microsomal mixed function oxidases may be inferred. 3. 1-Naphthyl-4(5)-imidazole, the most potent inhibitor of hydroxylation of drugs and estrogen rings A and B, also inhibited microsomal estrogen-16alpha-hydroxylation. 4. These data show that insecticide synergists may effect the breakdown of estrogenic hormones in the organism.", "contents": "Effects of insecticide synergists on microsomal oxidation of estradiol and ethynylestradiol and on microsomal drug metabolism. 1. Oxidation of estradiol and ethynylestradiol at ring A and ring B by rat liver microsomes and NADPH-regenerating system in vitro is inhibited by the two arylimidazole insecticide synergists, 3-bromophenyl-4(5)-imidazole and 1-naphthyl-4(5)-imidazole, but not by the benzothiadiazole insectide synergists 6-nitro-1,2,3-benzothiadiazole and 5,6-dimethyl-1,2,3-benzothiadiazole. The Ki of the most potent inhibitor, 1-naphthyl-4(5)-imidazole, was 3 X 10(-6) M. 2. 6-Nitro-1,2,3-benzothiadiazole (10(-6) M), which did not inhibit hydroxylation of the estrogens, inhibited oxidation of aniline and demethylation of ethylmorphine, p-nitroanisole, and aminopyrine by 30-70%. 5,6-Dimethyl-1,2,3-benzothiadiazole inhibited only demethylation of p-nitroanisole and aminopyrine. From these results the presence of different hepatic microsomal mixed function oxidases may be inferred. 3. 1-Naphthyl-4(5)-imidazole, the most potent inhibitor of hydroxylation of drugs and estrogen rings A and B, also inhibited microsomal estrogen-16alpha-hydroxylation. 4. These data show that insecticide synergists may effect the breakdown of estrogenic hormones in the organism."} {"id": "PMID:1274369", "title": "Metabolism of etidocaine in man.", "content": "1. Etidocaine and eight metabolites excreted in urine of man have been detected by g.l.c. and investigated by g.l.c.-mass spectrometry. 2. Five metabolites have been identified by comparison with authentic compounds as 2-amino-2'-butyroxylidide, 2-N-ethylamino-2'-butyroxylidide, 2-N-propylamino-2'-butyroxylidide, 2.6-dimethylaniline and 4-hydroxy-2,6-dimethylaniline. 3. The structure of one of the remaining three metabolites is proposed to be 2-methyl-N3-(2,6-dimethylphenyl)-5-ethyl-4-imidazolidinone. 4. The amounts of etidocaine and seven of its metabolites excreted in a 48 h urine following epidural administration to a patient have been estimated. Approx. 31% of the dose was accounted for.", "contents": "Metabolism of etidocaine in man. 1. Etidocaine and eight metabolites excreted in urine of man have been detected by g.l.c. and investigated by g.l.c.-mass spectrometry. 2. Five metabolites have been identified by comparison with authentic compounds as 2-amino-2'-butyroxylidide, 2-N-ethylamino-2'-butyroxylidide, 2-N-propylamino-2'-butyroxylidide, 2.6-dimethylaniline and 4-hydroxy-2,6-dimethylaniline. 3. The structure of one of the remaining three metabolites is proposed to be 2-methyl-N3-(2,6-dimethylphenyl)-5-ethyl-4-imidazolidinone. 4. The amounts of etidocaine and seven of its metabolites excreted in a 48 h urine following epidural administration to a patient have been estimated. Approx. 31% of the dose was accounted for."} {"id": "PMID:1274370", "title": "Reaction pathways of in vivo stereoselective conversion of ethylbenzene to (-)-mandelic acid.", "content": "1. Mandelic acid formed in vivo from ethylbenzene as well as from various oxidation intermediates was laevo mandelic acid and was of surprisingly high optical purity. 2. Reaction sequences are proposed for the stepwise oxidation of ethylbenzene to mandelic acid. 3. Although the initial hydroxylation of ethylbenzene to methylphenyl-carbinol is stereoselective, the optical activity of mandelic acid is not established at this point since the optical centre is destroyed in the second step, dehydrogenation to acetopheneone. 4. Acetophenone appears to be a precursor of not only mandelic acid and benzoylformic acid but benzoic acid as well. 5. The route from acetophenone involves conversion to omega-hydroxyacetophenone and subsequent reduction to glycol and/or oxidation to phenylglyoxal. 6. The configuration of mandelic acid is determined either during reduction of hydroxyacetophenone or reduction of phenylglyoxal.", "contents": "Reaction pathways of in vivo stereoselective conversion of ethylbenzene to (-)-mandelic acid. 1. Mandelic acid formed in vivo from ethylbenzene as well as from various oxidation intermediates was laevo mandelic acid and was of surprisingly high optical purity. 2. Reaction sequences are proposed for the stepwise oxidation of ethylbenzene to mandelic acid. 3. Although the initial hydroxylation of ethylbenzene to methylphenyl-carbinol is stereoselective, the optical activity of mandelic acid is not established at this point since the optical centre is destroyed in the second step, dehydrogenation to acetopheneone. 4. Acetophenone appears to be a precursor of not only mandelic acid and benzoylformic acid but benzoic acid as well. 5. The route from acetophenone involves conversion to omega-hydroxyacetophenone and subsequent reduction to glycol and/or oxidation to phenylglyoxal. 6. The configuration of mandelic acid is determined either during reduction of hydroxyacetophenone or reduction of phenylglyoxal."} {"id": "PMID:1274371", "title": "Bile and urine as complementary pathways for the excretion of foreign organic compounds.", "content": "1. The urinary and biliary excretion in the rat of 30 aromatic compounds with mol. wt. of 100-850, and largely excreted unchanged, has been studied. 2. These compounds fall into three groups as regards their pattern of elimination, which is related to mol. wt: group 1, with mol. wt. less than 350 and the major route of elimination the urine. When urinary excretion is prevented by ligating the renal pedicles the biliary excretion remains low. group 2, with mol, wt. of 450-850 which are excreted predominantly in bile. Even when the bile duct is obstructed, only small amounts of these compounds are found in urine. group 3, with mol. wt. of 350-450, which are eliminated extensively in both urine and bile. When one of these routes is blocked excretion by the other increases. 3. These studies emphasize the interrelationship of urine and bile as excretory routes for organic compounds. Urine and bile are complementary pathways; the extent of urinary excretion is greatest for the compounds of lowest mol. wt. and tends to decrease as mol. wt. increases and biliary excretion becomes more extensive.", "contents": "Bile and urine as complementary pathways for the excretion of foreign organic compounds. 1. The urinary and biliary excretion in the rat of 30 aromatic compounds with mol. wt. of 100-850, and largely excreted unchanged, has been studied. 2. These compounds fall into three groups as regards their pattern of elimination, which is related to mol. wt: group 1, with mol. wt. less than 350 and the major route of elimination the urine. When urinary excretion is prevented by ligating the renal pedicles the biliary excretion remains low. group 2, with mol, wt. of 450-850 which are excreted predominantly in bile. Even when the bile duct is obstructed, only small amounts of these compounds are found in urine. group 3, with mol. wt. of 350-450, which are eliminated extensively in both urine and bile. When one of these routes is blocked excretion by the other increases. 3. These studies emphasize the interrelationship of urine and bile as excretory routes for organic compounds. Urine and bile are complementary pathways; the extent of urinary excretion is greatest for the compounds of lowest mol. wt. and tends to decrease as mol. wt. increases and biliary excretion becomes more extensive."} {"id": "PMID:1274372", "title": "Comparative metabolic study of nimetazepam and its desmethyl derivative (nitrazepam) in dogs.", "content": "1. Blood levels of nimetazepam after oral administration to dogs were relatively low at early periods after dosage and reached peak levels (7-7-7-9 mug equiv./ml) after 8 h. The time course of blood levels was similar after oral administration of its desmethyl derivative (nitrazepam) to dogs. Blood levels of the latter, however, were low compared with nimetazepam and reached a peak (5-2-6-3 mug equiv./ml) after 4 h. 2. Recoveries of nimetazepam in urine and faeces were 46 and 52% of the dose for 0-24 h, 27 and 34% for 24-48 h and 4 and 6% for 48-72 h, while those of its desmethyl derivative (nitrazepam) were 63 and 71% for 0-24 h, 12 and 21% for 24-48 h and 2 and 3% for 48-72 h. 3. At least four kinds of reaction were involved in the biotransformation of nimetazepam and its desmethyl derivative (nitrazepam): (i) demethylation at N-1 (ii) hydroxylation at C-3, (iii) subsequent glucuronic acid conjugation of 3-hydroxy derivatives and (iv) reduction of the nitro group at C-7 to an amino group. Reaction (i) proceeded very rapidly in dogs, so that the blood metabolites of nimetazepam were closely similar to those of nitrazepam. For both drugs, the major blood metabolite was nitrazepam. Reaction (ii) was rapidly followed by reaction (iii), and glucuronides were predominantly excreted in urine. Reaction (iv) as well as reaction (iii) are important in the excretion of both drugs. The subsequent acetylation of 7-amino group, however, did not occur in dogs as it did in mice and rats.", "contents": "Comparative metabolic study of nimetazepam and its desmethyl derivative (nitrazepam) in dogs. 1. Blood levels of nimetazepam after oral administration to dogs were relatively low at early periods after dosage and reached peak levels (7-7-7-9 mug equiv./ml) after 8 h. The time course of blood levels was similar after oral administration of its desmethyl derivative (nitrazepam) to dogs. Blood levels of the latter, however, were low compared with nimetazepam and reached a peak (5-2-6-3 mug equiv./ml) after 4 h. 2. Recoveries of nimetazepam in urine and faeces were 46 and 52% of the dose for 0-24 h, 27 and 34% for 24-48 h and 4 and 6% for 48-72 h, while those of its desmethyl derivative (nitrazepam) were 63 and 71% for 0-24 h, 12 and 21% for 24-48 h and 2 and 3% for 48-72 h. 3. At least four kinds of reaction were involved in the biotransformation of nimetazepam and its desmethyl derivative (nitrazepam): (i) demethylation at N-1 (ii) hydroxylation at C-3, (iii) subsequent glucuronic acid conjugation of 3-hydroxy derivatives and (iv) reduction of the nitro group at C-7 to an amino group. Reaction (i) proceeded very rapidly in dogs, so that the blood metabolites of nimetazepam were closely similar to those of nitrazepam. For both drugs, the major blood metabolite was nitrazepam. Reaction (ii) was rapidly followed by reaction (iii), and glucuronides were predominantly excreted in urine. Reaction (iv) as well as reaction (iii) are important in the excretion of both drugs. The subsequent acetylation of 7-amino group, however, did not occur in dogs as it did in mice and rats."} {"id": "PMID:1274373", "title": "Urinary excretion of methaqualone-N-oxide in man.", "content": "1. Oral administration of therapeutic doses (250 mg) of methaqualone (Melsed) to adult human subjects gives rise to the urinary excretion of methaqualone-N-oxide. This metabolite has been identified by chromatography and mass spectrometry and quantitatively determined by reduction with titanium trichloride to methaqualone which was then determined by g.l.c. 2. The N-oxide accounts for 5-9% of the dose in 24 h. 3. 2-Nitrobenzo-o-toluidide, a possible oxidation product of methaqualone-N-oxide, has not been detected. 4. The urinary excretion of unchanged methaqualone is less than 0-3% of the dose. The ease with which methaqualone-N-oxide is thermally converted to methaqualone casts doubts on the previously published figures for the urinary excretion of methaqualone.", "contents": "Urinary excretion of methaqualone-N-oxide in man. 1. Oral administration of therapeutic doses (250 mg) of methaqualone (Melsed) to adult human subjects gives rise to the urinary excretion of methaqualone-N-oxide. This metabolite has been identified by chromatography and mass spectrometry and quantitatively determined by reduction with titanium trichloride to methaqualone which was then determined by g.l.c. 2. The N-oxide accounts for 5-9% of the dose in 24 h. 3. 2-Nitrobenzo-o-toluidide, a possible oxidation product of methaqualone-N-oxide, has not been detected. 4. The urinary excretion of unchanged methaqualone is less than 0-3% of the dose. The ease with which methaqualone-N-oxide is thermally converted to methaqualone casts doubts on the previously published figures for the urinary excretion of methaqualone."} {"id": "PMID:1274374", "title": "Urinary excretion of c-hydroxy derivatives of methaqualone in man.", "content": "1. Six monohydroxy metabolites of methaqualone have been identified by g.l.c.-mass spectrometry in the urine of healthy human subjects who received therapeutic doses (250 mg) of the drug (Melsed) daily for ten day. 2. The three major metabolites were 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone, 2-methyl-3-(2'-methyl-3'-hydroxyphenyl)-4(3H)-quinazolinone and 2-methyl-3-(2'-methyl-4'-hydroxyphenyl)-4(3H)-quinazolinone. Three minor metabolites in descending order of importance were 2-hydroxymethyl-3-o-tolyl-4(3H)-quinazolinone, 2-methyl-6-hydroxy-3-o-tolyl-4(3H)-quinazolinone and 2-methyl-8-hydroxy-3-o-tolyl-4(3H)-quinazolinone. 3. The 8-hydroxy metabolite is identified as a urinary metabolite or methaqualone in humans for the first time.", "contents": "Urinary excretion of c-hydroxy derivatives of methaqualone in man. 1. Six monohydroxy metabolites of methaqualone have been identified by g.l.c.-mass spectrometry in the urine of healthy human subjects who received therapeutic doses (250 mg) of the drug (Melsed) daily for ten day. 2. The three major metabolites were 2-methyl-3-(2'-hydroxymethylphenyl)-4(3H)-quinazolinone, 2-methyl-3-(2'-methyl-3'-hydroxyphenyl)-4(3H)-quinazolinone and 2-methyl-3-(2'-methyl-4'-hydroxyphenyl)-4(3H)-quinazolinone. Three minor metabolites in descending order of importance were 2-hydroxymethyl-3-o-tolyl-4(3H)-quinazolinone, 2-methyl-6-hydroxy-3-o-tolyl-4(3H)-quinazolinone and 2-methyl-8-hydroxy-3-o-tolyl-4(3H)-quinazolinone. 3. The 8-hydroxy metabolite is identified as a urinary metabolite or methaqualone in humans for the first time."} {"id": "PMID:1274375", "title": "Development of liver microsomal oxidations in the chick.", "content": "1. Liver microsomal preparations from chick embryos (1 day before hatching) and from 1-7 day old chicks were assayed for oxidative drug-metabolizing activity with aminopyrine, aniline and naphthalene as substrates. 2. Activities for all three substrates were highest in preparations from 1 day-old chicks. These were more than twice as active as the 7 day-old preparations and about three times as active as those from the embryos. 3. The increase in drug-metabolizing activities in newly-hatched chicks was the same for either sex and persisted for 3 days before declining towards the 7 day-old levels. 4. The developmental time-course fo the liver microsomal drug-metabolizing activities was independent of any factor in the 105 000 g supernatant fractions and of such microsomal parameters as cytochrome b5 and cytochrome P-450 content, and NADPH-cytochrome c reductase activity, but was related to changes in NADPH-cytochrome P-450 reductase levels. 5. Treatment of 7 day-old chicks with exogenous inducers, 3-methylcholanthrene or phenobarbital sodium (100 mg/kg, intraperitoneally) brought about maximal stimulation of microsomal activity as 18-24 h. The time-course of this induction was reflected by changes in microsomal cytochrome P-450 content and NADPH-cytochrome P=450 reductase activities. 6. Some induction of liver microsomal drug metabolism in 7 day-old chicks could also be brought about by injecting certain lipid-soluble egg yolk extracts.", "contents": "Development of liver microsomal oxidations in the chick. 1. Liver microsomal preparations from chick embryos (1 day before hatching) and from 1-7 day old chicks were assayed for oxidative drug-metabolizing activity with aminopyrine, aniline and naphthalene as substrates. 2. Activities for all three substrates were highest in preparations from 1 day-old chicks. These were more than twice as active as the 7 day-old preparations and about three times as active as those from the embryos. 3. The increase in drug-metabolizing activities in newly-hatched chicks was the same for either sex and persisted for 3 days before declining towards the 7 day-old levels. 4. The developmental time-course fo the liver microsomal drug-metabolizing activities was independent of any factor in the 105 000 g supernatant fractions and of such microsomal parameters as cytochrome b5 and cytochrome P-450 content, and NADPH-cytochrome c reductase activity, but was related to changes in NADPH-cytochrome P-450 reductase levels. 5. Treatment of 7 day-old chicks with exogenous inducers, 3-methylcholanthrene or phenobarbital sodium (100 mg/kg, intraperitoneally) brought about maximal stimulation of microsomal activity as 18-24 h. The time-course of this induction was reflected by changes in microsomal cytochrome P-450 content and NADPH-cytochrome P=450 reductase activities. 6. Some induction of liver microsomal drug metabolism in 7 day-old chicks could also be brought about by injecting certain lipid-soluble egg yolk extracts."} {"id": "PMID:1274376", "title": "Metabolism of 3-(hydroxymethyl)-8-methoxychromone in the rat. I. Absorption, tissue distribution and excretion.", "content": "1. Two 14C-labelled preparations of 3-(hydroxymethyl)-8-methoxychromone were used to study the absorption, tissue distribution and excretion of isotope after oral administration to rats (20 mg/kg). 2. 14C, presumably from the labelled hydroxymethyl side-chain, was eliminated extensively as 14CO2. This excretion was triphasic; kinetic constants were calculated for each phase. 3. The major excretion route was via the kidney although significant quantities of isotope were excreted with the faeces. Isotope did not accumulate in tissues.", "contents": "Metabolism of 3-(hydroxymethyl)-8-methoxychromone in the rat. I. Absorption, tissue distribution and excretion. 1. Two 14C-labelled preparations of 3-(hydroxymethyl)-8-methoxychromone were used to study the absorption, tissue distribution and excretion of isotope after oral administration to rats (20 mg/kg). 2. 14C, presumably from the labelled hydroxymethyl side-chain, was eliminated extensively as 14CO2. This excretion was triphasic; kinetic constants were calculated for each phase. 3. The major excretion route was via the kidney although significant quantities of isotope were excreted with the faeces. Isotope did not accumulate in tissues."} {"id": "PMID:1274377", "title": "Metabolism of 3-(hydroxymethyl)-8-methoxychromone in the rat. II. Classification and identification of urinary drug metabolites.", "content": "1. Five metabolites were isolated from the urine of dogs dosed with 3-(hydroxymethyl)-8-methoxy[4-14C]chromone. These were identified as 8-methoxychromone, 2-hydroxy-3-methoxyacetophenone, 3-(hydroxymethyl)-8-hydroxychromone, 8-hydroxychromone and 2,3-dihydroxyacetophenone. 2. These compounds were also present in the urine of rats treated with labelled drug, together with unchanged drug and two intermediate metabolites, 3-carboxy-8-methoxychromone and 3-(carboxymethyl)-8-hydroxychromone. 3. In addition to the unconjugated labelled compounds, glucuronides and sulphates were identified. 4. Quantitative data were obtained for all of the 20 labelled compounds in rat urine. 5. A scheme is presented for the biotransformation of 3-(hydroxymethyl)-8-methoxychromone in rats and dogs, and a mechanism for scission of the gamma-pyrone ring is suggested.", "contents": "Metabolism of 3-(hydroxymethyl)-8-methoxychromone in the rat. II. Classification and identification of urinary drug metabolites. 1. Five metabolites were isolated from the urine of dogs dosed with 3-(hydroxymethyl)-8-methoxy[4-14C]chromone. These were identified as 8-methoxychromone, 2-hydroxy-3-methoxyacetophenone, 3-(hydroxymethyl)-8-hydroxychromone, 8-hydroxychromone and 2,3-dihydroxyacetophenone. 2. These compounds were also present in the urine of rats treated with labelled drug, together with unchanged drug and two intermediate metabolites, 3-carboxy-8-methoxychromone and 3-(carboxymethyl)-8-hydroxychromone. 3. In addition to the unconjugated labelled compounds, glucuronides and sulphates were identified. 4. Quantitative data were obtained for all of the 20 labelled compounds in rat urine. 5. A scheme is presented for the biotransformation of 3-(hydroxymethyl)-8-methoxychromone in rats and dogs, and a mechanism for scission of the gamma-pyrone ring is suggested."} {"id": "PMID:1274378", "title": "Metabolism of alkenebenzene derivatives in the rat. II. Eugenol and isoeugenol methyl ethers.", "content": "1. The metabolites of 3,4-dimethoxyallylbenzene (eugenol methyl ether) and 3,4-dimethoxypropenylbenzene (isoeugenol methyl ether) in the rat were identified and quantitatively determined by g.l.c. and g.l.c.-mass spectrometry. 2. The major metabolic reactions of 3,4-dimethoxyallylbenzene were oxidation of the allylic side chain to 2-hydroxy-3-(3,4-dimethoxyphenyl)-propionic acid, 3,4-dimethoxybenzoic acid and 3,4-dimethoxycinnamic acid, the two latter being largely excreted as their glycine conjugates. The formation of the hydroxy acid presumably involved epoxidation of the double bond and subsequent hydration to the diol whereas the formation of 3,4-dimethoxycinnamic acid and 3,4-dimethoxybenzoic acid involved migration of the double bond and the formation of cinnamoyl intermediates. Other reactions were O-demethylation to 4-hydroxy-3-methoxyallylbenzene (eugenol) and 3-hydroxy-4-methoxyallylbenzene in equal amounts, oxidation to 1-(3,4-dimethoxyphenyl)-2-propen-1-ol, hydroxylation of the benzene ring to a hydroxy-3,4-dimethoxyallylbenzene and oxidation to 3,4-dimethoxyphenylacetic acid. The formation of 1-(3,4-dihydroxyphenyl)propane was found to be carried out by the rat intestinal micro-organisms. A total of at least 63% but as much as 95% dose was accounted for. 3. The major metabolic pathway of 3,4-dimethoxypropenylbenzene was via the cinnamoyl derivatives, leading to the formation of 4-hydroxy-3-methoxycinnamic acid (ferulic acid), 3,4-dimethoxycinnamic acid and 3,4-dimethoxybenzoic acid, the two latter being excreted largely as their glycine conjugates. Other reactions were O-demethylation to 4-hydroxy-3-methoxypropenylbenzene (isoeugenol) and 3-hydroxy-4-methoxypropenylbenzene in equal amounts, and oxidation to 3,4-dimethoxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetone. Epoxidation of the side chain appeared to be a minor metabolic reaction with the propenyl derivative. 4. The biliary metabolites of 3,4-dimethoxyallylbenzene and 3,4-dimethoxypropenylbenzene were identified and most of the urinary metabolites were also found in the bile.", "contents": "Metabolism of alkenebenzene derivatives in the rat. II. Eugenol and isoeugenol methyl ethers. 1. The metabolites of 3,4-dimethoxyallylbenzene (eugenol methyl ether) and 3,4-dimethoxypropenylbenzene (isoeugenol methyl ether) in the rat were identified and quantitatively determined by g.l.c. and g.l.c.-mass spectrometry. 2. The major metabolic reactions of 3,4-dimethoxyallylbenzene were oxidation of the allylic side chain to 2-hydroxy-3-(3,4-dimethoxyphenyl)-propionic acid, 3,4-dimethoxybenzoic acid and 3,4-dimethoxycinnamic acid, the two latter being largely excreted as their glycine conjugates. The formation of the hydroxy acid presumably involved epoxidation of the double bond and subsequent hydration to the diol whereas the formation of 3,4-dimethoxycinnamic acid and 3,4-dimethoxybenzoic acid involved migration of the double bond and the formation of cinnamoyl intermediates. Other reactions were O-demethylation to 4-hydroxy-3-methoxyallylbenzene (eugenol) and 3-hydroxy-4-methoxyallylbenzene in equal amounts, oxidation to 1-(3,4-dimethoxyphenyl)-2-propen-1-ol, hydroxylation of the benzene ring to a hydroxy-3,4-dimethoxyallylbenzene and oxidation to 3,4-dimethoxyphenylacetic acid. The formation of 1-(3,4-dihydroxyphenyl)propane was found to be carried out by the rat intestinal micro-organisms. A total of at least 63% but as much as 95% dose was accounted for. 3. The major metabolic pathway of 3,4-dimethoxypropenylbenzene was via the cinnamoyl derivatives, leading to the formation of 4-hydroxy-3-methoxycinnamic acid (ferulic acid), 3,4-dimethoxycinnamic acid and 3,4-dimethoxybenzoic acid, the two latter being excreted largely as their glycine conjugates. Other reactions were O-demethylation to 4-hydroxy-3-methoxypropenylbenzene (isoeugenol) and 3-hydroxy-4-methoxypropenylbenzene in equal amounts, and oxidation to 3,4-dimethoxyphenylacetic acid and 4-hydroxy-3-methoxyphenylacetone. Epoxidation of the side chain appeared to be a minor metabolic reaction with the propenyl derivative. 4. The biliary metabolites of 3,4-dimethoxyallylbenzene and 3,4-dimethoxypropenylbenzene were identified and most of the urinary metabolites were also found in the bile."} {"id": "PMID:1274379", "title": "The effect of prolonged administration of allylisopropylacetylurea to rats on cytochrome P-450 and other liver haemoproteins.", "content": "1. The effect of long-term administration, including recovery, of allylisopropylacetylurea to rats was investigated. 2. In the liver, cytochromes P-450, b5, catalase and 5-aminolaevulinic acid synthetase were measured. Serum glutamate-pyruvate, transaminase, glutamate-oxalacetate transaminase and alkaline phophatase were determined to assess cell damage, while urinary coproporphyrin and uroporphyrin were measured to assess the degree of porphyia. 3. In the liver the lowering of cytochrome P-450 and catalase was paralleled by an increase in 5-aminolaevulinate synthetase. Cytochrome b5 was only marginally affected. 4. Rats recover well from long-term treatment with high doses of allylisopropylacetylurea and revert to normal values for parameters measured. 5. A mechanism for the intracellular action of allylisopropylacetylurea on cytochrome P-450 and other haem-containing compounds is presented.", "contents": "The effect of prolonged administration of allylisopropylacetylurea to rats on cytochrome P-450 and other liver haemoproteins. 1. The effect of long-term administration, including recovery, of allylisopropylacetylurea to rats was investigated. 2. In the liver, cytochromes P-450, b5, catalase and 5-aminolaevulinic acid synthetase were measured. Serum glutamate-pyruvate, transaminase, glutamate-oxalacetate transaminase and alkaline phophatase were determined to assess cell damage, while urinary coproporphyrin and uroporphyrin were measured to assess the degree of porphyia. 3. In the liver the lowering of cytochrome P-450 and catalase was paralleled by an increase in 5-aminolaevulinate synthetase. Cytochrome b5 was only marginally affected. 4. Rats recover well from long-term treatment with high doses of allylisopropylacetylurea and revert to normal values for parameters measured. 5. A mechanism for the intracellular action of allylisopropylacetylurea on cytochrome P-450 and other haem-containing compounds is presented."} {"id": "PMID:1274380", "title": "Stereospecific inversion of l-alpha-methylfluorene-2-acetic acid to its d-enantiomer in the dog.", "content": "1. After administration of dl-alpha-methylfluorene-2-acetic acid to dogs, the optical rotation of the drug in blood increased with time. Of the total drug in blood, the d-enantiomer increased from 61 to 80% between 3 and 24 h after administration; by 384 h it was 100%. 2. Both l- and d-enantiomers had plasma half-lives and excretion characteristics similar to those of the dl-racemic mixture, indicating that the increase in the proportion of the d-enantiomer was not due to more rapid excretion of the l-enantiomer. 3. Studies of optical rotation and circular dichroism demonstrated that the l-enantiomer was converted to the d-enantiomer in the blood of the dog, but the d-enantiomer remained unchanged. After administration of the l-enantiomer, the d-enantiomer increased from 26 to 71% of the total drug in blood between 0-3 and 2 days after administration; 14 days after dosing, almost all of the drug was present as the d-enantiomer. 4. Isomerization of l-alpha-methylfluorene-2-acetic acid to its d-enantiomer also occurs in rat, monkey and man.", "contents": "Stereospecific inversion of l-alpha-methylfluorene-2-acetic acid to its d-enantiomer in the dog. 1. After administration of dl-alpha-methylfluorene-2-acetic acid to dogs, the optical rotation of the drug in blood increased with time. Of the total drug in blood, the d-enantiomer increased from 61 to 80% between 3 and 24 h after administration; by 384 h it was 100%. 2. Both l- and d-enantiomers had plasma half-lives and excretion characteristics similar to those of the dl-racemic mixture, indicating that the increase in the proportion of the d-enantiomer was not due to more rapid excretion of the l-enantiomer. 3. Studies of optical rotation and circular dichroism demonstrated that the l-enantiomer was converted to the d-enantiomer in the blood of the dog, but the d-enantiomer remained unchanged. After administration of the l-enantiomer, the d-enantiomer increased from 26 to 71% of the total drug in blood between 0-3 and 2 days after administration; 14 days after dosing, almost all of the drug was present as the d-enantiomer. 4. Isomerization of l-alpha-methylfluorene-2-acetic acid to its d-enantiomer also occurs in rat, monkey and man."} {"id": "PMID:1274381", "title": "Metabolism of a benzothiazine compound (SQ 11,579) by the intact rat, isolated perfused rat liver, and rat-liver microsomes.", "content": "1. The metabolic dispositions of a benzothiazine compound (SQ 11,579) by the intact rat, isolated perfused rat liver, and rat-liver microsomes have been investigated, and the results compared. 2. The drug was well absorbed after oral administration to rats and was widely distributed in all tissues, which, with the exception of brain, had higher concentrations of the drug, its metabolites, or both, than did plasma. 3. Metabolism by rat-liver microsomes included N-oxidation, N-demethylation, S-oxidation and aryl hydroxylation. Metabolites hydroxylated in the aromatic ring were excreted only in bile, both by the isolated perfused rat livers and by anaesthetized bile-duct-cannulated rats. 4. Liver perfusion of the benzothiazine or its monodesmethyl analogue (V) resulted in temporary cessation of the flow of perfusate through the organ. The benzothiazine sulphoxide (IV) had only a slight effect on the flow of liver perfusate, but IV followed by I caused the flow of perfusate to cease.", "contents": "Metabolism of a benzothiazine compound (SQ 11,579) by the intact rat, isolated perfused rat liver, and rat-liver microsomes. 1. The metabolic dispositions of a benzothiazine compound (SQ 11,579) by the intact rat, isolated perfused rat liver, and rat-liver microsomes have been investigated, and the results compared. 2. The drug was well absorbed after oral administration to rats and was widely distributed in all tissues, which, with the exception of brain, had higher concentrations of the drug, its metabolites, or both, than did plasma. 3. Metabolism by rat-liver microsomes included N-oxidation, N-demethylation, S-oxidation and aryl hydroxylation. Metabolites hydroxylated in the aromatic ring were excreted only in bile, both by the isolated perfused rat livers and by anaesthetized bile-duct-cannulated rats. 4. Liver perfusion of the benzothiazine or its monodesmethyl analogue (V) resulted in temporary cessation of the flow of perfusate through the organ. The benzothiazine sulphoxide (IV) had only a slight effect on the flow of liver perfusate, but IV followed by I caused the flow of perfusate to cease."} {"id": "PMID:1274382", "title": "Metabolism in rats and man of piromidic acid, a new antibacterial agent.", "content": "1. Metabolism of the antibacterial, piromidic acid (5,8-dihydro-8-ethyl-5-oxo-2-pyrrolidinopyrido[2,3-d]pyrimidine-6-carboxylic acid) was investigated in rats and human subjects. Ten metabolites and the unchanged drug were found in the urine and the bile of both species after oral administration. 2. Metabolites were identified by comparison with authentic materials, except for the unstable metabolite, M-VI, for which a probable structure is proposed. The metabolic pathway of piromidic acid involved hydroxylation in the pyrrolidine ring to give the 2- and 3-hydroxy-derivatives (M-II and M-V). M-II was further metabolized to the corresponding gamma-aminobutyric acid derivative (M-IV) and the 2-5-dihydroxypyrrolidine derivative (M-VI) which was further metabolized to the 2-amino-pyridopyrimidine carboxylic acid (M-III). Piromidic acid, M-V, M-II, M-III and M-IV were partly excreted as respective glucuronides. 3. Metabolites, except glucuronides, exhibited antibacterial activity; M-V and M-II showed greater activity than piromidic acid. 4. The metabolism of piromidic acid is discussed in relation to the physicochemical properties of the drug and its metabolites.", "contents": "Metabolism in rats and man of piromidic acid, a new antibacterial agent. 1. Metabolism of the antibacterial, piromidic acid (5,8-dihydro-8-ethyl-5-oxo-2-pyrrolidinopyrido[2,3-d]pyrimidine-6-carboxylic acid) was investigated in rats and human subjects. Ten metabolites and the unchanged drug were found in the urine and the bile of both species after oral administration. 2. Metabolites were identified by comparison with authentic materials, except for the unstable metabolite, M-VI, for which a probable structure is proposed. The metabolic pathway of piromidic acid involved hydroxylation in the pyrrolidine ring to give the 2- and 3-hydroxy-derivatives (M-II and M-V). M-II was further metabolized to the corresponding gamma-aminobutyric acid derivative (M-IV) and the 2-5-dihydroxypyrrolidine derivative (M-VI) which was further metabolized to the 2-amino-pyridopyrimidine carboxylic acid (M-III). Piromidic acid, M-V, M-II, M-III and M-IV were partly excreted as respective glucuronides. 3. Metabolites, except glucuronides, exhibited antibacterial activity; M-V and M-II showed greater activity than piromidic acid. 4. The metabolism of piromidic acid is discussed in relation to the physicochemical properties of the drug and its metabolites."} {"id": "PMID:1274383", "title": "Delayed type hypersensitivity in guinea pig infected subcutaneously with Naegleria fowleri Carter.", "content": "A soluble fraction, derived from Naegleria fowleri trophozoites disrupted by freeze-thawing, was tested for antigenic properties. Intradermal injections of this preparation were administered to guinea pigs previously infected subcutaneously with viable N. fowleri. Delayed hypersensitivity to the antigen and loss of weight, the diagnostic symptom of visceral naegleriasis, were observed in the surviving animals. Fifty percent of the guinea pigs, however, did not lose weight and had a reduced reaction to the antigen. The apparent differences in the immunocompetence of guinea pigs inoculated subcutaneously and intranasally with N. fowleri are compared.", "contents": "Delayed type hypersensitivity in guinea pig infected subcutaneously with Naegleria fowleri Carter. A soluble fraction, derived from Naegleria fowleri trophozoites disrupted by freeze-thawing, was tested for antigenic properties. Intradermal injections of this preparation were administered to guinea pigs previously infected subcutaneously with viable N. fowleri. Delayed hypersensitivity to the antigen and loss of weight, the diagnostic symptom of visceral naegleriasis, were observed in the surviving animals. Fifty percent of the guinea pigs, however, did not lose weight and had a reduced reaction to the antigen. The apparent differences in the immunocompetence of guinea pigs inoculated subcutaneously and intranasally with N. fowleri are compared."} {"id": "PMID:1274384", "title": "Prevalence and pathology of Hepatojarakus bandicoti Sood et Parshad, 1973 (Trichostrongylidae:Nematoda) in natural infections of rodents.", "content": "The prevalence and pathological changes in the liver and biliary system of field rodents due to Hepatojarakus bandicoti Sood et Parshad, 1973 have been worked out. Higher infection rates occurred in Tatera indica and Bandicota bengalensis than in other field rats and mice. In heavy infections, the liver became grossly enlarged, hard and pale, and showed the presence of white scars on its surface and in the parenchyma. White nodules are commonly seen on the bile ducts due to heavy infections. Histologically the liver showed a changed lobular structure, cellular infiltrations, pycnotic nuclei of the hepatic cells with deposition of haemosidirin granules. Hypermorphosis of the biliary epithelium with its denudation, resulting from the creeping action of the worm seemed to be a common tissue response.", "contents": "Prevalence and pathology of Hepatojarakus bandicoti Sood et Parshad, 1973 (Trichostrongylidae:Nematoda) in natural infections of rodents. The prevalence and pathological changes in the liver and biliary system of field rodents due to Hepatojarakus bandicoti Sood et Parshad, 1973 have been worked out. Higher infection rates occurred in Tatera indica and Bandicota bengalensis than in other field rats and mice. In heavy infections, the liver became grossly enlarged, hard and pale, and showed the presence of white scars on its surface and in the parenchyma. White nodules are commonly seen on the bile ducts due to heavy infections. Histologically the liver showed a changed lobular structure, cellular infiltrations, pycnotic nuclei of the hepatic cells with deposition of haemosidirin granules. Hypermorphosis of the biliary epithelium with its denudation, resulting from the creeping action of the worm seemed to be a common tissue response."} {"id": "PMID:1274385", "title": "Schistosomiasis at Loum, Cameroun; Schistosoma haematobium, S. intercalatum and their natural hybrid.", "content": "A survey of 500 schoolchildren in Loum in 1968 revealed an overall infection rate of 54.2% with Schistosoma intercalatum and this was the only species of schistosome encountered. In 1972 a number of children were found to be passing schistosome eggs in their urine and these eggs ranged in shape and size from the forms characteristic for S. haematobium to those of S. intercalatum. Preliminary laboratory studies demonstrated that hybridisation between the two species was occurring. Subsequent field surveys showed that the snail hosts for the two parasites (B. rohlfsi for S. haematobium and B. forskali for S. intercalatum) were both present in the river Mbette and its tributaries in Loum and the distribution of the two snail species coincided closely with the distribution of the schistosomes in the human population. Detailed study of a small group of children passing hybrid eggs in their urine revealed that few of them were passing eggs in their faeces and that those eggs which were found in faeces were not viable. Analysis of schistosome egg-shape by plotting cumulative size-frequency data on probability paper demonstrated that the graph obtained from a natural hybrid series was different from that given by a known mixture of the two separate species. The hybrid series included a number of exceptionally large eggs resembling those of S. bovis but isolation of these eggs and subsequent laboratory passage of the parasites showed that they were part of the series and were not evidence of the presence of a third species. Hybridisation experiments in the laboratory showed that the cross S. haematobium male X S. intercalatum femal is fully viable but that the reverse mating is not successful, thus accounting for the failure of the faecal eggs recovered from children with hybrid infections. Histological results from laboratory passaged hybrids suggest that the Ziehl-positive staining reaction of the egg-shells of S. intercalatum may be a recessive character. The observations reported here indicate that S. haematobium has only recently become established in Loum and that it is, through introgressive hybridisation, replacing the indigenous S. intercalatum. A suggested explanation for the change in the parasite fauna is offered and this depends upon ecological changes resulting from forest clearance and agricultural development providing improved conditions for the spread of B. rohlfsi, the snail host for S. haematobium. It is suggested that, in contrast to recent reports on the spread of S. intercalatum, this species is in fact retreating and being replaced by S. haematobium in areas where forest clearance is taking place. In conclusion it is suggested that introgressive hybridisation of this kind may have been responsible for the evolution of certain characteristic local strains of African schistosomes.", "contents": "Schistosomiasis at Loum, Cameroun; Schistosoma haematobium, S. intercalatum and their natural hybrid. A survey of 500 schoolchildren in Loum in 1968 revealed an overall infection rate of 54.2% with Schistosoma intercalatum and this was the only species of schistosome encountered. In 1972 a number of children were found to be passing schistosome eggs in their urine and these eggs ranged in shape and size from the forms characteristic for S. haematobium to those of S. intercalatum. Preliminary laboratory studies demonstrated that hybridisation between the two species was occurring. Subsequent field surveys showed that the snail hosts for the two parasites (B. rohlfsi for S. haematobium and B. forskali for S. intercalatum) were both present in the river Mbette and its tributaries in Loum and the distribution of the two snail species coincided closely with the distribution of the schistosomes in the human population. Detailed study of a small group of children passing hybrid eggs in their urine revealed that few of them were passing eggs in their faeces and that those eggs which were found in faeces were not viable. Analysis of schistosome egg-shape by plotting cumulative size-frequency data on probability paper demonstrated that the graph obtained from a natural hybrid series was different from that given by a known mixture of the two separate species. The hybrid series included a number of exceptionally large eggs resembling those of S. bovis but isolation of these eggs and subsequent laboratory passage of the parasites showed that they were part of the series and were not evidence of the presence of a third species. Hybridisation experiments in the laboratory showed that the cross S. haematobium male X S. intercalatum femal is fully viable but that the reverse mating is not successful, thus accounting for the failure of the faecal eggs recovered from children with hybrid infections. Histological results from laboratory passaged hybrids suggest that the Ziehl-positive staining reaction of the egg-shells of S. intercalatum may be a recessive character. The observations reported here indicate that S. haematobium has only recently become established in Loum and that it is, through introgressive hybridisation, replacing the indigenous S. intercalatum. A suggested explanation for the change in the parasite fauna is offered and this depends upon ecological changes resulting from forest clearance and agricultural development providing improved conditions for the spread of B. rohlfsi, the snail host for S. haematobium. It is suggested that, in contrast to recent reports on the spread of S. intercalatum, this species is in fact retreating and being replaced by S. haematobium in areas where forest clearance is taking place. In conclusion it is suggested that introgressive hybridisation of this kind may have been responsible for the evolution of certain characteristic local strains of African schistosomes."} {"id": "PMID:1274386", "title": "Protein metabolism in Isoparorchis hypselobagri.", "content": "Isoparorchis hypselobagri was maintained in a non-nutrient medium containing streptomycin and penicillin to prevent bacterial growth for a period of 12 hours. The parasites were kept under aerobic conditions at a suitable temperature of 30 degrees C. The protein content in Isoparorchis hypselobagri ranged from 56.25% to 67.5% with an average of 63.5%+/-4.6 of dry seight of the tissue. The nitrogen of Isoparorchis hypselobagri excreted as ammonia, after 12 hours of starvation was 3.04% of the total body nitrogen and as uric acid 1.6% of total body nitrogen.", "contents": "Protein metabolism in Isoparorchis hypselobagri. Isoparorchis hypselobagri was maintained in a non-nutrient medium containing streptomycin and penicillin to prevent bacterial growth for a period of 12 hours. The parasites were kept under aerobic conditions at a suitable temperature of 30 degrees C. The protein content in Isoparorchis hypselobagri ranged from 56.25% to 67.5% with an average of 63.5%+/-4.6 of dry seight of the tissue. The nitrogen of Isoparorchis hypselobagri excreted as ammonia, after 12 hours of starvation was 3.04% of the total body nitrogen and as uric acid 1.6% of total body nitrogen."} {"id": "PMID:1274387", "title": "Amino acid composition in Isoparorchis hypselobagri.", "content": "The free amino acids of Isoparorchis hypselobagri have been determined by the chromatographic method (two-dimensional ascending). These are: leucine, valine, proline, alanine, glycine, glutamic acid and aspartic acid.", "contents": "Amino acid composition in Isoparorchis hypselobagri. The free amino acids of Isoparorchis hypselobagri have been determined by the chromatographic method (two-dimensional ascending). These are: leucine, valine, proline, alanine, glycine, glutamic acid and aspartic acid."} {"id": "PMID:1274388", "title": "[The ultrastructure of the intraerythrocytic stages of Babesia herpailuri-trophozoites and merozoites after treatment with imidocarb (3,3'-bis-2-imidazolin-2-yl)-carbanilide (author's transl)].", "content": "The fine structure of trophozoites and especially of merozoites of Babesia herpailuri is described before and after treatment with Imidocarb (Wellcome). The mostly piriform to oval merozoites possess an outer membrane and a supporting membrane below. The intratorium consists of a polar ring, rhoptries micronemes and the sperical body which lies beside the big nucleus and next to mitochondria. The endoplasmic reticulum and invaginations are not clearly formed. The cellular changes of Babesia herpailuri, observed one hour after drug treatment in trophozoites and six hours later in merozoites, concern the form and function of the parasite: widening of the subpellicular endoplasmic reticulum and of the perinuclear space; sporadic dilatation of the endoplasmic reticulum of the merozoites (9 fig.). Damaged membranes, dissolution of the cellular membrane, disintegration of the nuclei as are known effects of the Berenil treatment to Babesia herpailuri, are not noted results after the Imidocarb treatment. The original membrane systems of trophozoites as well as of merozoites, remain unaffected by the drug as long as investigations were carried on (24 h). The satisfying prophylactic effect of Imidocarb as well as the insignificant cellular damages on merozoites may be due to the small feeding of hemoglobin.", "contents": "[The ultrastructure of the intraerythrocytic stages of Babesia herpailuri-trophozoites and merozoites after treatment with imidocarb (3,3'-bis-2-imidazolin-2-yl)-carbanilide (author's transl)]. The fine structure of trophozoites and especially of merozoites of Babesia herpailuri is described before and after treatment with Imidocarb (Wellcome). The mostly piriform to oval merozoites possess an outer membrane and a supporting membrane below. The intratorium consists of a polar ring, rhoptries micronemes and the sperical body which lies beside the big nucleus and next to mitochondria. The endoplasmic reticulum and invaginations are not clearly formed. The cellular changes of Babesia herpailuri, observed one hour after drug treatment in trophozoites and six hours later in merozoites, concern the form and function of the parasite: widening of the subpellicular endoplasmic reticulum and of the perinuclear space; sporadic dilatation of the endoplasmic reticulum of the merozoites (9 fig.). Damaged membranes, dissolution of the cellular membrane, disintegration of the nuclei as are known effects of the Berenil treatment to Babesia herpailuri, are not noted results after the Imidocarb treatment. The original membrane systems of trophozoites as well as of merozoites, remain unaffected by the drug as long as investigations were carried on (24 h). The satisfying prophylactic effect of Imidocarb as well as the insignificant cellular damages on merozoites may be due to the small feeding of hemoglobin."} {"id": "PMID:1274389", "title": "[Late complications after cross-plate arthrodesis of the hip (author's transl)].", "content": "Cross-plate arthrodesis produces a problem of incongruence which cannot be solved by surgical skill Mechanical factors, not foreseeable before operation, produce an inevitable divergence of pulling and torsion forces with a high risk of losening of the implant and pseudarthrosis, particularly when the acetabulum is degenerated. The mechanical forces are shown in Fig. 6. The review of our cases shows that healing after cross-plate arthrodesis may follow three pathways.", "contents": "[Late complications after cross-plate arthrodesis of the hip (author's transl)]. Cross-plate arthrodesis produces a problem of incongruence which cannot be solved by surgical skill Mechanical factors, not foreseeable before operation, produce an inevitable divergence of pulling and torsion forces with a high risk of losening of the implant and pseudarthrosis, particularly when the acetabulum is degenerated. The mechanical forces are shown in Fig. 6. The review of our cases shows that healing after cross-plate arthrodesis may follow three pathways."} {"id": "PMID:1274390", "title": "[The acetabular roof formation of the operative treatment in CDH (author's transl)].", "content": "The acetabular roof construction is discussed in the open reductions, pelvic osteotomy and derotational osteotomy. Open reduction under 18 manth old, if without secondary change of the femoral head, gets sufficient acetabular covering. Pelvic osteotomy as the reconstructive manoeuver around 3 years old can also get a good acetabular condition.", "contents": "[The acetabular roof formation of the operative treatment in CDH (author's transl)]. The acetabular roof construction is discussed in the open reductions, pelvic osteotomy and derotational osteotomy. Open reduction under 18 manth old, if without secondary change of the femoral head, gets sufficient acetabular covering. Pelvic osteotomy as the reconstructive manoeuver around 3 years old can also get a good acetabular condition."} {"id": "PMID:1274391", "title": "[Regeneration of the synovia (author's transl)].", "content": "Thirteen knee joints of dogs were synovectomized, rearthrotomized after various periods of time and the capsule tissue histologically and submicroscopically evaluated. The synovial cell layer is differentiated into histiocytes and fibroblasts which are genetically related to the local fibrocytes of the remaining tissue or to the mononuclear cell elements of the blood. The cells produce a synovial membrane which rarely differs from the normal membrane. The prerequisite is functional stress. Fourteen weeks after the synovectomy, a normal ultrastructure was formed. The synovia was then capable of bearing strain. The regression of the dystrophic cartilage alterations, the adaptability of the cells to the altered demands and the particular cytoplasmatic structuring of the various cell types are to be understood as an expression of the efficiency of the synovial membrane. Clinical and therapeutic consequences were discussed. In regard to regeneration of the synovia in the diseased joint, a regeneration phase, an efficiency phase and an alteration phase were differentiated.", "contents": "[Regeneration of the synovia (author's transl)]. Thirteen knee joints of dogs were synovectomized, rearthrotomized after various periods of time and the capsule tissue histologically and submicroscopically evaluated. The synovial cell layer is differentiated into histiocytes and fibroblasts which are genetically related to the local fibrocytes of the remaining tissue or to the mononuclear cell elements of the blood. The cells produce a synovial membrane which rarely differs from the normal membrane. The prerequisite is functional stress. Fourteen weeks after the synovectomy, a normal ultrastructure was formed. The synovia was then capable of bearing strain. The regression of the dystrophic cartilage alterations, the adaptability of the cells to the altered demands and the particular cytoplasmatic structuring of the various cell types are to be understood as an expression of the efficiency of the synovial membrane. Clinical and therapeutic consequences were discussed. In regard to regeneration of the synovia in the diseased joint, a regeneration phase, an efficiency phase and an alteration phase were differentiated."} {"id": "PMID:1274392", "title": "[The articular capsule in idiopathic hypertrophic osteoarthropathy (author's transl)].", "content": "The results of clinical roentgenological, cytological examinations as well as the histological examination of biopsy material with electron microscopy are reported for two cases of primary idiopathic hypertrophic osteoarthropathy. In both cases, a watchglass nail was present in the hands and feet; clubbed, distended knee, ankle and wrist joints; appositional enlargement of the shaft of the long bones; the hands and the phalanges of the foot as well as arthralgia and an hyperhidrosis. The morphological examination of biopsy material confirmed the already established increased periosteal bone enlargement. In addition, a fibrosis of the synovial membrane with thickening of the fibrous tissue matrix and increased vascularization of the synovial membrane could be established. Inflammatory processes could be excluded. The reported findings could be attributed to a generalized defect in hormonal or enzymatic regulation of the mesenchym. The vascularization can be explained as a reaction to the lengthening of the transit route between vessels and joint lumen. The thickening of the connective tissue together with the lengthening of the transit route is considered to be an essential causal factor in the arthralgic complaints of strain in hypertrophic osteoarthropathy.", "contents": "[The articular capsule in idiopathic hypertrophic osteoarthropathy (author's transl)]. The results of clinical roentgenological, cytological examinations as well as the histological examination of biopsy material with electron microscopy are reported for two cases of primary idiopathic hypertrophic osteoarthropathy. In both cases, a watchglass nail was present in the hands and feet; clubbed, distended knee, ankle and wrist joints; appositional enlargement of the shaft of the long bones; the hands and the phalanges of the foot as well as arthralgia and an hyperhidrosis. The morphological examination of biopsy material confirmed the already established increased periosteal bone enlargement. In addition, a fibrosis of the synovial membrane with thickening of the fibrous tissue matrix and increased vascularization of the synovial membrane could be established. Inflammatory processes could be excluded. The reported findings could be attributed to a generalized defect in hormonal or enzymatic regulation of the mesenchym. The vascularization can be explained as a reaction to the lengthening of the transit route between vessels and joint lumen. The thickening of the connective tissue together with the lengthening of the transit route is considered to be an essential causal factor in the arthralgic complaints of strain in hypertrophic osteoarthropathy."} {"id": "PMID:1274393", "title": "[The brown coloring of the permanent cartilage tissue in old age (author's transl)].", "content": "The brown coloring of the permanent cartilage tissue in old age (demonstrated at the rib cartilage) is to be related to pigment deposition in cartilage cells and ground substance. There is a granular pigment present, which probably is a chromolipid. Unstained histological slides are best suitable for the presentation of pigments. In epiphysial joint cartilage (transitory cartilage tissue) the pigmentation of aging usually is only suggested. The appearance of pigment granulas is accompanied by various regressive alterations of cartilage tissue, especially with eosinophilia of the ground substance.", "contents": "[The brown coloring of the permanent cartilage tissue in old age (author's transl)]. The brown coloring of the permanent cartilage tissue in old age (demonstrated at the rib cartilage) is to be related to pigment deposition in cartilage cells and ground substance. There is a granular pigment present, which probably is a chromolipid. Unstained histological slides are best suitable for the presentation of pigments. In epiphysial joint cartilage (transitory cartilage tissue) the pigmentation of aging usually is only suggested. The appearance of pigment granulas is accompanied by various regressive alterations of cartilage tissue, especially with eosinophilia of the ground substance."} {"id": "PMID:1274394", "title": "[Morbid anatomy and pathogenesis of spondylolysis and spondylolysthesis in childhood (author's transl)].", "content": "Histologic findings of 4 cases of spondylolysis and spondylolisthesis in childhood and their pathogenetic interpretation. The microscopic changes in the lateral gap of the vertebral arch in children are explained as due to stress in the growing intervertebral bones, as fatigue fractures in the widest sense, with a tendency to pathologic union and fibro-cartilagineous pseudarthrosis. During pathogenesis we distinguish between the \"primary lysis\", a stage of repair followed by defective healing and the resulting spondylolysis.", "contents": "[Morbid anatomy and pathogenesis of spondylolysis and spondylolysthesis in childhood (author's transl)]. Histologic findings of 4 cases of spondylolysis and spondylolisthesis in childhood and their pathogenetic interpretation. The microscopic changes in the lateral gap of the vertebral arch in children are explained as due to stress in the growing intervertebral bones, as fatigue fractures in the widest sense, with a tendency to pathologic union and fibro-cartilagineous pseudarthrosis. During pathogenesis we distinguish between the \"primary lysis\", a stage of repair followed by defective healing and the resulting spondylolysis."} {"id": "PMID:1274395", "title": "[Distal symphalangia with humeroradial synostosis, carpal synostosis and brachyphalangia of the thumb. A dominant syndrome (author's transl)].", "content": "In a family with genetically dominant joint aplasia, 12 of the 27 involved members in four generations had bilateral humeroradial synostoses; the rest, ventral luxation of the radius. In addition, various degrees of malformations and aplasia of the carpal, tarsal and interphalangeal joints as well as shortening of the proximal phalanx of the thumb were observed. All other similar cases described in the available literature differ significantly from those described here.", "contents": "[Distal symphalangia with humeroradial synostosis, carpal synostosis and brachyphalangia of the thumb. A dominant syndrome (author's transl)]. In a family with genetically dominant joint aplasia, 12 of the 27 involved members in four generations had bilateral humeroradial synostoses; the rest, ventral luxation of the radius. In addition, various degrees of malformations and aplasia of the carpal, tarsal and interphalangeal joints as well as shortening of the proximal phalanx of the thumb were observed. All other similar cases described in the available literature differ significantly from those described here."} {"id": "PMID:1274396", "title": "[Basic documentation by nonmedical personnel in an Orthopedic University Hospital (author's transl)].", "content": "A report was presented concerning the experience with the basic documentation of stationary and ambulatory patients in an orthopedic hospital for which the diagnostic code and the orthopedic-surgical code from the Commission for \"Orthopedic Documentation\" of the DGOT proved successful. It was particularly interesting to note that the same results were obtained by nonmedical personnel on the basic documentation as by interns and residents.", "contents": "[Basic documentation by nonmedical personnel in an Orthopedic University Hospital (author's transl)]. A report was presented concerning the experience with the basic documentation of stationary and ambulatory patients in an orthopedic hospital for which the diagnostic code and the orthopedic-surgical code from the Commission for \"Orthopedic Documentation\" of the DGOT proved successful. It was particularly interesting to note that the same results were obtained by nonmedical personnel on the basic documentation as by interns and residents."} {"id": "PMID:1274397", "title": "[Knee joint prosthesis with the geomedic knee joint (author's transl)].", "content": "Thirty-one cases of plastic knee joint operations were reported. Twenty-one patients were treated with the geomedic knee. The advantage of this joint is that only a small amount of bone must be sacraficed. The range of movement is better than that with a complete knee prosthesis with axis.", "contents": "[Knee joint prosthesis with the geomedic knee joint (author's transl)]. Thirty-one cases of plastic knee joint operations were reported. Twenty-one patients were treated with the geomedic knee. The advantage of this joint is that only a small amount of bone must be sacraficed. The range of movement is better than that with a complete knee prosthesis with axis."} {"id": "PMID:1274398", "title": "[The position of the supracondylar correction osteotomie during the treatment of the senile gonarthrosis (author's transl)].", "content": "The position of the supracondylar correction osteotomie during the treatment of the senile gonarthrosis is examined by controls of 17 patients with 21 performed osteotomies. The indication, the technique as well as the clinical and radiological results of the operation are critically dealt with. In case of a correct indication and when considering the contra-indication-like and existing strong osteoporosis, a distinct deficit of expansion and a most serious arthrosis-good results can be expected.", "contents": "[The position of the supracondylar correction osteotomie during the treatment of the senile gonarthrosis (author's transl)]. The position of the supracondylar correction osteotomie during the treatment of the senile gonarthrosis is examined by controls of 17 patients with 21 performed osteotomies. The indication, the technique as well as the clinical and radiological results of the operation are critically dealt with. In case of a correct indication and when considering the contra-indication-like and existing strong osteoporosis, a distinct deficit of expansion and a most serious arthrosis-good results can be expected."} {"id": "PMID:1274399", "title": "[About early operative treatment of osteochondrosis dissecans of the knee (author's transl)].", "content": "There is a report about eleven cases of juvenile osteochondrosis dissecans of knee-joints. In many cases symptoms are uncharacteristic. Therefore, exact X-ray-diagnostic is essential. Early operation by pinning with Smillie-pins seems justified. The nails remain, as the growth of the bone allows them to sink into the interior of the femoral condyles without harm. Observations during longer periods show good results. Apparently, this method of leaving pins in the bone has never been reported before.", "contents": "[About early operative treatment of osteochondrosis dissecans of the knee (author's transl)]. There is a report about eleven cases of juvenile osteochondrosis dissecans of knee-joints. In many cases symptoms are uncharacteristic. Therefore, exact X-ray-diagnostic is essential. Early operation by pinning with Smillie-pins seems justified. The nails remain, as the growth of the bone allows them to sink into the interior of the femoral condyles without harm. Observations during longer periods show good results. Apparently, this method of leaving pins in the bone has never been reported before."} {"id": "PMID:1274400", "title": "[Localisation and pathogenesis of Morton's metatarsalgia (author's transl)].", "content": "Todays concept of Morton's metatarsalgia is seen as a pseudoneuroma of the plantar digital nerve. Since clinic and pathogenesis tally, one should abandon the idea that Morton's metatarsalgia consists of interdigital pain (mainly in the 3rd space) and accept it as a pfeudoneuroma due mainly to pressure on the plantar digital nerve.", "contents": "[Localisation and pathogenesis of Morton's metatarsalgia (author's transl)]. Todays concept of Morton's metatarsalgia is seen as a pseudoneuroma of the plantar digital nerve. Since clinic and pathogenesis tally, one should abandon the idea that Morton's metatarsalgia consists of interdigital pain (mainly in the 3rd space) and accept it as a pfeudoneuroma due mainly to pressure on the plantar digital nerve."} {"id": "PMID:1274401", "title": "[Gout, pseudo-gout or hyperlipoproteinemia? (author's transl)].", "content": "A number of patients with aseptic necroses of bone and hyperlipoproteinemia of types II and IV after Fredrickson are reported on. More than one half of them had hyperuricemia without symptoms of gout. The relationship between fat-, purine- and carbohydrate-metabolism are discussed. The clinical pictures of hyperuricemia, gout and hyperlipoproteinemia are shown to resemble each other. Differential diagnosis, particularly as related to aseptic necroses of bone, is discussed in detail.", "contents": "[Gout, pseudo-gout or hyperlipoproteinemia? (author's transl)]. A number of patients with aseptic necroses of bone and hyperlipoproteinemia of types II and IV after Fredrickson are reported on. More than one half of them had hyperuricemia without symptoms of gout. The relationship between fat-, purine- and carbohydrate-metabolism are discussed. The clinical pictures of hyperuricemia, gout and hyperlipoproteinemia are shown to resemble each other. Differential diagnosis, particularly as related to aseptic necroses of bone, is discussed in detail."} {"id": "PMID:1274402", "title": "[A contribution to the origin of lordotic curved back through persisting abdominal breathing (pBA) (author's transl)].", "content": "Man, once quadrupedal, purchased his erect posture at the cost of back problems arising in middle age if he does not successfully convert from quadrupedal (abdominal) breathing to bipedal (chest) breathing. Many persisting abdominal breathers (pBA) at rest go to health spas 4-5 times or more at public expense in order to relieve their lower back pain. Due to the persisting abdominal breathing at rest, however, very little improvement in the condition is possible. We must discover abdominal breathers as small children between the ages of 2 and 4 in the routine medical check-ups and re-train them. If this is not accomplished, the failure of a small child to convert when he learns to walk costs the public many millions of unneccessary marks a few decades later.", "contents": "[A contribution to the origin of lordotic curved back through persisting abdominal breathing (pBA) (author's transl)]. Man, once quadrupedal, purchased his erect posture at the cost of back problems arising in middle age if he does not successfully convert from quadrupedal (abdominal) breathing to bipedal (chest) breathing. Many persisting abdominal breathers (pBA) at rest go to health spas 4-5 times or more at public expense in order to relieve their lower back pain. Due to the persisting abdominal breathing at rest, however, very little improvement in the condition is possible. We must discover abdominal breathers as small children between the ages of 2 and 4 in the routine medical check-ups and re-train them. If this is not accomplished, the failure of a small child to convert when he learns to walk costs the public many millions of unneccessary marks a few decades later."} {"id": "PMID:1274403", "title": "[Arm and hand prosthesis--today and in the future (author's transl)].", "content": "The hand must be taken in a required working position (necessary for eating, drinking, dressing and writing) in order it can touch and grasp. For that purpose a combined motion of all arm-joints is necessary. Hand-surgical procedures are of little value when the hand cannot be taken in such a working position. The problem of the upper arm prosthesis is the driving of the elbow because both the Hood-arm and the myoelectrically driven elbow joint bring no satisfactory functional results. The Tobelbader Hand is a self-powered prosthesis for patients who have a wrist stump. By means of this Tobelbader Hand the prehension can be dosed muscularly. The substitute of the amputated wrist by implantation of an endoprosthesis is discussed theoretically. For the first time to an amputee (with upper arm amputation on both sides) an endoprosthesis was implanted into the stump of the upper arm in order to drive the prosthetic elbow. By means of this artificial, however movable elbow joint the electrical artificial hand can be reliable taken into any wanted position for working.", "contents": "[Arm and hand prosthesis--today and in the future (author's transl)]. The hand must be taken in a required working position (necessary for eating, drinking, dressing and writing) in order it can touch and grasp. For that purpose a combined motion of all arm-joints is necessary. Hand-surgical procedures are of little value when the hand cannot be taken in such a working position. The problem of the upper arm prosthesis is the driving of the elbow because both the Hood-arm and the myoelectrically driven elbow joint bring no satisfactory functional results. The Tobelbader Hand is a self-powered prosthesis for patients who have a wrist stump. By means of this Tobelbader Hand the prehension can be dosed muscularly. The substitute of the amputated wrist by implantation of an endoprosthesis is discussed theoretically. For the first time to an amputee (with upper arm amputation on both sides) an endoprosthesis was implanted into the stump of the upper arm in order to drive the prosthetic elbow. By means of this artificial, however movable elbow joint the electrical artificial hand can be reliable taken into any wanted position for working."} {"id": "PMID:1274404", "title": "[Changing position of the neutral vertebra in different stages of curve correction (author's transl)].", "content": "During the curve correction especially by means of modern technics the position of the neutral vertebra may change. Therefore the curve after operative treatment should be measured between the new vertebral bodies in neutral position to avoid measurement mistakes. This challenge is of special interest in follow-up studies.", "contents": "[Changing position of the neutral vertebra in different stages of curve correction (author's transl)]. During the curve correction especially by means of modern technics the position of the neutral vertebra may change. Therefore the curve after operative treatment should be measured between the new vertebral bodies in neutral position to avoid measurement mistakes. This challenge is of special interest in follow-up studies."} {"id": "PMID:1274405", "title": "[Problems of experiments on rats in orthopedics (author's transl)].", "content": "A small experimental study on rats in orthopedics shows that it is impossible to achieve constant bipedy as a basis for valid static and biomechanic investigations, particularly of the spine.", "contents": "[Problems of experiments on rats in orthopedics (author's transl)]. A small experimental study on rats in orthopedics shows that it is impossible to achieve constant bipedy as a basis for valid static and biomechanic investigations, particularly of the spine."} {"id": "PMID:1274425", "title": "[The effect of iproniazid on biogenic amine levels, elaboration and reproduction of alimentary conditioned reflexes].", "content": "A study of the action of iproniaside on alimentary conditioning has shown that even its small doses (25 mg/kg) disturb the formation of the conditioned reaction, while large doses (200-250 mg/kg) do not disturb the reproduction of the conditioned reaction elaborated and stabilized before the administration of the drug. Hence, dissociated learning with the use of iproniaside is impossible. The applied doses of iproniaside result in an increased level of biogenic amines in the dopaminergic nigro-neostriate and reticulo-septal brain systems. It is therefore assumed that the effects of iproniaside on learning are due to its influence on the level of the CNS biogenic amines.", "contents": "[The effect of iproniazid on biogenic amine levels, elaboration and reproduction of alimentary conditioned reflexes]. A study of the action of iproniaside on alimentary conditioning has shown that even its small doses (25 mg/kg) disturb the formation of the conditioned reaction, while large doses (200-250 mg/kg) do not disturb the reproduction of the conditioned reaction elaborated and stabilized before the administration of the drug. Hence, dissociated learning with the use of iproniaside is impossible. The applied doses of iproniaside result in an increased level of biogenic amines in the dopaminergic nigro-neostriate and reticulo-septal brain systems. It is therefore assumed that the effects of iproniaside on learning are due to its influence on the level of the CNS biogenic amines."} {"id": "PMID:1274426", "title": "[The relationship between the frequency of self-stimulation and parameters of the stimulus].", "content": "The dependence of self-stimulation frequency on stimulation parameters (current intensity, stimulation frequency, pulse duration, duration of pulse bursts) was studied in fifteen rats with monopolar electrodes implanted in the lateral hypothalamus, using rectangular current pulses for brain stimulation. All the experiments revealed qualitatively similar response surfaces to the combined change of stimulation frequency and pulse duration Self-stimulation frequency is connected in a non-linear way with the \"specific charge\" per unit of time, and in an approximately linear way, with the duration of the pulse burst. Regression equations are determined which precisely enough described the kind of response surface (R =0.7 to 0.95).", "contents": "[The relationship between the frequency of self-stimulation and parameters of the stimulus]. The dependence of self-stimulation frequency on stimulation parameters (current intensity, stimulation frequency, pulse duration, duration of pulse bursts) was studied in fifteen rats with monopolar electrodes implanted in the lateral hypothalamus, using rectangular current pulses for brain stimulation. All the experiments revealed qualitatively similar response surfaces to the combined change of stimulation frequency and pulse duration Self-stimulation frequency is connected in a non-linear way with the \"specific charge\" per unit of time, and in an approximately linear way, with the duration of the pulse burst. Regression equations are determined which precisely enough described the kind of response surface (R =0.7 to 0.95)."} {"id": "PMID:1274427", "title": "[The effect of a decrease in cerebral noradrenaline concentrations on the formation and fixation of temporary connections].", "content": "A sharp drop in the noradrenaline content (Na) in the brain of mice does not prevent the elaboration and fixation of relatively simple conditioned reflexes, but considerably disturbs the elaboration of more complex conditioned reflexes with delayed reinforcement. The decrease in the NA content in the brain does not appear to influence directly the process of consolidation of temporary connections; impaired fixation of relatively more complex forms of temporary connections is of a secondary nature and is due to disturbances in their formation.", "contents": "[The effect of a decrease in cerebral noradrenaline concentrations on the formation and fixation of temporary connections]. A sharp drop in the noradrenaline content (Na) in the brain of mice does not prevent the elaboration and fixation of relatively simple conditioned reflexes, but considerably disturbs the elaboration of more complex conditioned reflexes with delayed reinforcement. The decrease in the NA content in the brain does not appear to influence directly the process of consolidation of temporary connections; impaired fixation of relatively more complex forms of temporary connections is of a secondary nature and is due to disturbances in their formation."} {"id": "PMID:1274428", "title": "[A comparison of problem solving by extrapolation before and after removal of the archicortex and Wulst in cows].", "content": "The change in the capacity for extrapolation was studied in crows after ablation of Wulst and the archicortex. After the ablation of the archicortex, the solution of the extrapolation problem does not change. After the ablation of Wulst, the number of \"refusals\" to solve increases, the number of correct responses diminishes, although it remains significantly higher than the number of errors. It is assumed that the archicortex and Wulst play no decisive part in the process of solving problems involving extrapolation; yet Wulst apparently controls the achievement of the final reaction, by-passing the screen.", "contents": "[A comparison of problem solving by extrapolation before and after removal of the archicortex and Wulst in cows]. The change in the capacity for extrapolation was studied in crows after ablation of Wulst and the archicortex. After the ablation of the archicortex, the solution of the extrapolation problem does not change. After the ablation of Wulst, the number of \"refusals\" to solve increases, the number of correct responses diminishes, although it remains significantly higher than the number of errors. It is assumed that the archicortex and Wulst play no decisive part in the process of solving problems involving extrapolation; yet Wulst apparently controls the achievement of the final reaction, by-passing the screen."} {"id": "PMID:1274430", "title": "[A neurophysiologic study of sleep in children during the first year of life].", "content": "Polygraphic investigation of day sleep has been carried out in thirty suckling infants (aged from 25 days to 12 months). EEG, OCG, SGR, respiration ECG, muscular activity, and in some infants, also rheographic parameters (REG and RG of the shin) have shown that already at an early nursing age, states of drowsiness, falling asleep, light and medium depth and deep slow sleep set in, as well as the so-called rapid sleep which occurs only after slow sleep. The denotation of the slow sleep stages is based on the classification by Loomis et al., though their electroenecepholographic expression in the infant is in many ways peculiar and undergoes certain dynamics during the first year of life. Peculiarities of the central area EEG have been exhibited in all the age groups, and it has been assumed that the central parts of the cortex of a suckling infant are a kind of \"window\" into the subcortical parts. While EEG, displaying new forms of activity at certain stages of sleep undergo distinct age changes, vegetative sleep manifestations display only some age depending quantitative differences. Thus, at the nursing age the mechanisms of electroencephalographic and vegetative sleep manifestations are of different degree of maturity: they possess a considerable autonomy, although they function in concord.", "contents": "[A neurophysiologic study of sleep in children during the first year of life]. Polygraphic investigation of day sleep has been carried out in thirty suckling infants (aged from 25 days to 12 months). EEG, OCG, SGR, respiration ECG, muscular activity, and in some infants, also rheographic parameters (REG and RG of the shin) have shown that already at an early nursing age, states of drowsiness, falling asleep, light and medium depth and deep slow sleep set in, as well as the so-called rapid sleep which occurs only after slow sleep. The denotation of the slow sleep stages is based on the classification by Loomis et al., though their electroenecepholographic expression in the infant is in many ways peculiar and undergoes certain dynamics during the first year of life. Peculiarities of the central area EEG have been exhibited in all the age groups, and it has been assumed that the central parts of the cortex of a suckling infant are a kind of \"window\" into the subcortical parts. While EEG, displaying new forms of activity at certain stages of sleep undergo distinct age changes, vegetative sleep manifestations display only some age depending quantitative differences. Thus, at the nursing age the mechanisms of electroencephalographic and vegetative sleep manifestations are of different degree of maturity: they possess a considerable autonomy, although they function in concord."} {"id": "PMID:1274431", "title": "[Spatial synchronization of cerebral cortical potentals at different levels of functioning of short-term verbal memory].", "content": "Spatial synchronization of cortical biopotentials was studied at different levels of the functioning of short-term verbal memory. In the phases prior to and during presentation of information the general level of distant synchronization in the cortex at a high functional state of the mnemical mechanism is higher than at a low state. In the phases following presentation and during reproduction, the relations are reverse. The enhancement of distant synchronization involves primarily the posterior parts of the right hemisphere, while the decrease comprises all the cortical areas, with some predominance of this effect in the anterior areas.", "contents": "[Spatial synchronization of cerebral cortical potentals at different levels of functioning of short-term verbal memory]. Spatial synchronization of cortical biopotentials was studied at different levels of the functioning of short-term verbal memory. In the phases prior to and during presentation of information the general level of distant synchronization in the cortex at a high functional state of the mnemical mechanism is higher than at a low state. In the phases following presentation and during reproduction, the relations are reverse. The enhancement of distant synchronization involves primarily the posterior parts of the right hemisphere, while the decrease comprises all the cortical areas, with some predominance of this effect in the anterior areas."} {"id": "PMID:1274432", "title": "[The relationship between the parameters of the early and late oscillations of human cortical evoked potentials and the rhythm of acoustic stimulation].", "content": "The amplitudes of all deflections of the slow auditory evoked potential (AEP) regularly decrease in alert subjects with the increase of stimulation rate. As compared with the late deflections (P2N2), the decrease of the amplitude of comparatively early deflections (N1P2) is more pronounced. It is a rather logarithmic, than a linear function of the interstimulus interval. The degree of amplitude diminution of slow AEPs due to a greater stimulation rate depends on the intensity of acoustic stimul: at greater sound intensities the decrease is more pronounced. The higher rates of stimulation produce, along with a decreased amplitude, a shorter peak latencies of all slow AEP deflections (except the peak of deflection P1). In narcotic (chloralhydrate) sleep higher rates of stimulation are not attended with any regular changes in the amplitude and peak latencies of the slow AEP.", "contents": "[The relationship between the parameters of the early and late oscillations of human cortical evoked potentials and the rhythm of acoustic stimulation]. The amplitudes of all deflections of the slow auditory evoked potential (AEP) regularly decrease in alert subjects with the increase of stimulation rate. As compared with the late deflections (P2N2), the decrease of the amplitude of comparatively early deflections (N1P2) is more pronounced. It is a rather logarithmic, than a linear function of the interstimulus interval. The degree of amplitude diminution of slow AEPs due to a greater stimulation rate depends on the intensity of acoustic stimul: at greater sound intensities the decrease is more pronounced. The higher rates of stimulation produce, along with a decreased amplitude, a shorter peak latencies of all slow AEP deflections (except the peak of deflection P1). In narcotic (chloralhydrate) sleep higher rates of stimulation are not attended with any regular changes in the amplitude and peak latencies of the slow AEP."} {"id": "PMID:1274433", "title": "[The topography of functional interhemispheric asymmetry in the visual cortex].", "content": "Functional interhemispheric asymmetry was investigated by evoked potentials method in experiments on ten cats under ethaminal anaesthesia at 200 points of the visual cortex during the action of binocular and monocular photic flashes of submaximal intensity. Topographic maps have been plotted of the functional interhemispheric asymmetry. In most of the animals a hemisphere dominant and non-dominant at the given moment can be singled out. Section of the callosal body leads to reduction of the functional interhemispheric asymmetry due to a decrease of the focus of maximum activity in the dominant hemisphere and its increase in the non-dominant one. A mozaic pattern of functional interhemispheric asymmetry has been demonstrated, as expressed in the existence of zones of inverse dominance along with prevailing zones of direct dominance. Section of the callosal body produced a decrease in the area of direct dominance and an increase in that of inverse dominance. Absolute interhemispheric asymmetry was most pronounced in the central part of the visual cortex (field 18 and its medial boundary) and the relative one, on the periphery of the visual area (fields 17 and 19).", "contents": "[The topography of functional interhemispheric asymmetry in the visual cortex]. Functional interhemispheric asymmetry was investigated by evoked potentials method in experiments on ten cats under ethaminal anaesthesia at 200 points of the visual cortex during the action of binocular and monocular photic flashes of submaximal intensity. Topographic maps have been plotted of the functional interhemispheric asymmetry. In most of the animals a hemisphere dominant and non-dominant at the given moment can be singled out. Section of the callosal body leads to reduction of the functional interhemispheric asymmetry due to a decrease of the focus of maximum activity in the dominant hemisphere and its increase in the non-dominant one. A mozaic pattern of functional interhemispheric asymmetry has been demonstrated, as expressed in the existence of zones of inverse dominance along with prevailing zones of direct dominance. Section of the callosal body produced a decrease in the area of direct dominance and an increase in that of inverse dominance. Absolute interhemispheric asymmetry was most pronounced in the central part of the visual cortex (field 18 and its medial boundary) and the relative one, on the periphery of the visual area (fields 17 and 19)."} {"id": "PMID:1274434", "title": "[The role of the temporal neocortex in the origin of convulsive activity].", "content": "Experiments on cats with cooling capsules implanted over different areas of the neocortex have shown that cooling of different intensity applied to the temporal neocortex may result in both stimulation and switching off effects. Cold stimulation (temperature dropping to 27-33 degrees C) manifested in generalized epileptiform brain electrical activity and paroxysmal states. The functional switching off the temporal area observed during its deeper cooling (20-21 degrees C) discontinues the paroxysmal state already developed and prevents the appearance of seizures, regrardless of the localization of the epileptogenic focus. The paroxysmal state weakens and ceases after repeated cooling of the temporal neocortex. The temporal neocortex, involved in the integrated activating brain system, plays a decisive role in the emergence of paroxysmal states.", "contents": "[The role of the temporal neocortex in the origin of convulsive activity]. Experiments on cats with cooling capsules implanted over different areas of the neocortex have shown that cooling of different intensity applied to the temporal neocortex may result in both stimulation and switching off effects. Cold stimulation (temperature dropping to 27-33 degrees C) manifested in generalized epileptiform brain electrical activity and paroxysmal states. The functional switching off the temporal area observed during its deeper cooling (20-21 degrees C) discontinues the paroxysmal state already developed and prevents the appearance of seizures, regrardless of the localization of the epileptogenic focus. The paroxysmal state weakens and ceases after repeated cooling of the temporal neocortex. The temporal neocortex, involved in the integrated activating brain system, plays a decisive role in the emergence of paroxysmal states."} {"id": "PMID:1274435", "title": "[Characteristics of the super-slow electrical activity of the brain when exposed to the action of neurotropic substances altering short-term memory].", "content": "Superslow electrical activity was studied after the action of neurotropic drugs on curarized rabbits with gold electrodes implanted in the deep brain structures. Intramuscular administration of 1/5 mg/kg dose of ethimizol, of 5 mg/kg of ethipyrol, or of 1/5 mg/kg of metamizyl led to a reciprocity of the oscillation amplitudes between the field CA-3 of the dorsal hippocampus and the medial nuclear groups of the reticular formation. Ethimizol and ethipyrol, though producing a similar final effect, act differently on the duration and phases of slow oscillations. Micropolarization of the dorsal hippocampus field CA-3 with a 2.5 microampere current lengthened the action of the neurotropic drugs, up to six hours in the case of ethimyzol. A mathematical vector analysis has shown that the angle of the wave amplitude vector in space depends both on the characteristics of the neurotropic drug and the excitability level of field CA-3 of the dorsl hippo-campus. A slow electrical potential reflecting the capacity of the electric field of a brain structure is likely to be one the major components controlling the conformation position of the receptor proteins.", "contents": "[Characteristics of the super-slow electrical activity of the brain when exposed to the action of neurotropic substances altering short-term memory]. Superslow electrical activity was studied after the action of neurotropic drugs on curarized rabbits with gold electrodes implanted in the deep brain structures. Intramuscular administration of 1/5 mg/kg dose of ethimizol, of 5 mg/kg of ethipyrol, or of 1/5 mg/kg of metamizyl led to a reciprocity of the oscillation amplitudes between the field CA-3 of the dorsal hippocampus and the medial nuclear groups of the reticular formation. Ethimizol and ethipyrol, though producing a similar final effect, act differently on the duration and phases of slow oscillations. Micropolarization of the dorsal hippocampus field CA-3 with a 2.5 microampere current lengthened the action of the neurotropic drugs, up to six hours in the case of ethimyzol. A mathematical vector analysis has shown that the angle of the wave amplitude vector in space depends both on the characteristics of the neurotropic drug and the excitability level of field CA-3 of the dorsl hippo-campus. A slow electrical potential reflecting the capacity of the electric field of a brain structure is likely to be one the major components controlling the conformation position of the receptor proteins."} {"id": "PMID:1274440", "title": "[Hemispheric asymetry of the evoked electrical activity of the cerebral cortex to letter and non-verbal stimuli].", "content": "Average evoked potentials (AEP) were recorded in practically healthy subjects to \"meaningless\" figures and letters, presented to different halves of the visual field. Analysis of the amplitudes of AEP late components to verbal and non-verbal stimuli reveals hemispheric asymmetry. A higher amplitude of the late positive evoked response (P300) to a \"direct\" stimulation both by verbal and non-verbal stimuli (in the contralateral field of vision) is recorded in the left hemisphere than in the right one. Similar stimulation of the right hemisphere does not reveal sucha difference. In the left hemisphere the P300 wave is of a clearly greater amplitude to a \"direct\" stimulation (contralateral visual field) than to an \"indirect\" one (ipsilateral visual field), regardless of the nature of the stimulus. No such difference is observed in the right hemisphere. The magnitude of the late negative wave (component N200) to non-verbal stimuli is greater in the right hemisphere both in response to \"direct\" and \"indirect\" stimulations. No intrahemispheric difference has been found in the amplitude of late evoked responses of the cerebral cortex to verbal and non-verbal stimuli.", "contents": "[Hemispheric asymetry of the evoked electrical activity of the cerebral cortex to letter and non-verbal stimuli]. Average evoked potentials (AEP) were recorded in practically healthy subjects to \"meaningless\" figures and letters, presented to different halves of the visual field. Analysis of the amplitudes of AEP late components to verbal and non-verbal stimuli reveals hemispheric asymmetry. A higher amplitude of the late positive evoked response (P300) to a \"direct\" stimulation both by verbal and non-verbal stimuli (in the contralateral field of vision) is recorded in the left hemisphere than in the right one. Similar stimulation of the right hemisphere does not reveal sucha difference. In the left hemisphere the P300 wave is of a clearly greater amplitude to a \"direct\" stimulation (contralateral visual field) than to an \"indirect\" one (ipsilateral visual field), regardless of the nature of the stimulus. No such difference is observed in the right hemisphere. The magnitude of the late negative wave (component N200) to non-verbal stimuli is greater in the right hemisphere both in response to \"direct\" and \"indirect\" stimulations. No intrahemispheric difference has been found in the amplitude of late evoked responses of the cerebral cortex to verbal and non-verbal stimuli."} {"id": "PMID:1274446", "title": "[The neuronal organization of a focus of conditioned excitation in the cat sensory-motor cortex].", "content": "The activity of single units in the focus of conditioned excitation was studied during defensive conditioning to direct electrical stimulation of the cat sensorimotor cortex. Reorganizations of spike activity set in during the period of reflex elaboration, were manifest in the increased number of excited neurones and those which respond both to the conditioned and unconditioned stimuli. In the course of elaboration, the inhibitory phase of unit responses to direct electrical stimulation of the sensorimotor cortex was reduced, while the frequency of background unit spike activity was enhanced. Acute extinction of the reflex restored the initial duration of the inhibitory phase and reduced the frequency of the background activity.", "contents": "[The neuronal organization of a focus of conditioned excitation in the cat sensory-motor cortex]. The activity of single units in the focus of conditioned excitation was studied during defensive conditioning to direct electrical stimulation of the cat sensorimotor cortex. Reorganizations of spike activity set in during the period of reflex elaboration, were manifest in the increased number of excited neurones and those which respond both to the conditioned and unconditioned stimuli. In the course of elaboration, the inhibitory phase of unit responses to direct electrical stimulation of the sensorimotor cortex was reduced, while the frequency of background unit spike activity was enhanced. Acute extinction of the reflex restored the initial duration of the inhibitory phase and reduced the frequency of the background activity."} {"id": "PMID:1274447", "title": "[The activity of cat motor cortex neurons during performance of a conditoned response of placing the forepaw on a support].", "content": "The activity of 74 units of the cat precentral motor cortex was studied in the process of reaction of placing the forepaw on a support. It has been shown that the neurones controlling the flexion of the ulnar joint, the first phase of the reaction, receive an afferent tactile input primarily from the dorsal side of the paw, i.e. from region of the skin surface which is the receptive field of the reflex of placing the paw on the support. Learning the animals to lift the paw to the support in response to a touch of the ventral surface results in an increase of discharge frequency of the studied units in response to ventral stimulation similar to that recorded in response to the initially effective dorsal stimulation.", "contents": "[The activity of cat motor cortex neurons during performance of a conditoned response of placing the forepaw on a support]. The activity of 74 units of the cat precentral motor cortex was studied in the process of reaction of placing the forepaw on a support. It has been shown that the neurones controlling the flexion of the ulnar joint, the first phase of the reaction, receive an afferent tactile input primarily from the dorsal side of the paw, i.e. from region of the skin surface which is the receptive field of the reflex of placing the paw on the support. Learning the animals to lift the paw to the support in response to a touch of the ventral surface results in an increase of discharge frequency of the studied units in response to ventral stimulation similar to that recorded in response to the initially effective dorsal stimulation."} {"id": "PMID:1274448", "title": "[Electrographically present and trace conditioned reactions to complex stimuli in man].", "content": "In experiments on 48 human subjects aged from 16 to 25 years, elaboration of present reactions to a complex stimulus was accompanied by stabilization of SGR not only in response to the first, triggering, and the last, reinforcing, components of the complex stimulus, but also to its central element provided it was a proprioceptive signal. In addition, SGR magnitude at the moment of the stimuli action was more considerable during the formation of trace processes as compared with one observed during elaboration of present reactions. The results obtained lead to the assumption that reproduction of excitation traces is preceded by the brain estimation of the time equal to the interstimuli pause.", "contents": "[Electrographically present and trace conditioned reactions to complex stimuli in man]. In experiments on 48 human subjects aged from 16 to 25 years, elaboration of present reactions to a complex stimulus was accompanied by stabilization of SGR not only in response to the first, triggering, and the last, reinforcing, components of the complex stimulus, but also to its central element provided it was a proprioceptive signal. In addition, SGR magnitude at the moment of the stimuli action was more considerable during the formation of trace processes as compared with one observed during elaboration of present reactions. The results obtained lead to the assumption that reproduction of excitation traces is preceded by the brain estimation of the time equal to the interstimuli pause."} {"id": "PMID:1274449", "title": "EEG correlation and impulse activity of neuronal populations of individual structures of the cat brain during elaboration and reproduction of motor and alimentary reactions in instrumental conditioned reflexes.", "content": "Stable changes in EEG and spike activity of neuronal populations in different brain formations were studied on models of instrumental conditioned reflexes: motor and motor alimentary. A depencence has been established of the EEG amplitude-frequency parameters in the motor and striate cortical zones and the hippocampus on definite changes of unit spike activity in these areas. Simultaneous recording of the EEG and the spike activity of neuronal populations helps to elucidate the neurophysiological nature of individual rhythms of bio-electrical activity. Learned animals exhibit a stable reproduction of the spatial-temporal EEG patterns and motor alimentary reactions when automatic presentation of reinforcement is changed over to an arbitrary one.", "contents": "EEG correlation and impulse activity of neuronal populations of individual structures of the cat brain during elaboration and reproduction of motor and alimentary reactions in instrumental conditioned reflexes. Stable changes in EEG and spike activity of neuronal populations in different brain formations were studied on models of instrumental conditioned reflexes: motor and motor alimentary. A depencence has been established of the EEG amplitude-frequency parameters in the motor and striate cortical zones and the hippocampus on definite changes of unit spike activity in these areas. Simultaneous recording of the EEG and the spike activity of neuronal populations helps to elucidate the neurophysiological nature of individual rhythms of bio-electrical activity. Learned animals exhibit a stable reproduction of the spatial-temporal EEG patterns and motor alimentary reactions when automatic presentation of reinforcement is changed over to an arbitrary one."} {"id": "PMID:1274450", "title": "[The effect of cryogenic exclusion of the neocortex on preservation of the functioning of its temporal regions].", "content": "In chronic experiments on nine cats a study was made of different forms of their behavior in conditions of cold elimination of the cerebral cortex with the exception of the temporal areas. The first sessions of cooling produced a diminution of alimentary excitability, enhanced motor activity, loss of the reaction of mouse chasing and of a defensive reaction against the dog, and a disappearance of previously elaborated conditioned runnings to the feeding trough, etc. In the course of subsequent experiments with the neocortex cooling, the disturbed forms of behavior were restored. In the second and third sessions alimentary excitation was considerably restored; by the sixth and seventh sessions motor activity became normal, while the 20th to 25th sessions exhibited a protective reaction against the dog. Conditioned runnings restored in the seventinth session were manifest in the 20th to 25th sessions in 80% of cases. It is assumed that the temporal areas of the neocortex while playing a considerable part in integrating the activity of the whole brain, including the formation and manifestation of conditioned reflexes, under normal conditions, to a large extent lose their integrative role when the rest of the neocortex is elimated.", "contents": "[The effect of cryogenic exclusion of the neocortex on preservation of the functioning of its temporal regions]. In chronic experiments on nine cats a study was made of different forms of their behavior in conditions of cold elimination of the cerebral cortex with the exception of the temporal areas. The first sessions of cooling produced a diminution of alimentary excitability, enhanced motor activity, loss of the reaction of mouse chasing and of a defensive reaction against the dog, and a disappearance of previously elaborated conditioned runnings to the feeding trough, etc. In the course of subsequent experiments with the neocortex cooling, the disturbed forms of behavior were restored. In the second and third sessions alimentary excitation was considerably restored; by the sixth and seventh sessions motor activity became normal, while the 20th to 25th sessions exhibited a protective reaction against the dog. Conditioned runnings restored in the seventinth session were manifest in the 20th to 25th sessions in 80% of cases. It is assumed that the temporal areas of the neocortex while playing a considerable part in integrating the activity of the whole brain, including the formation and manifestation of conditioned reflexes, under normal conditions, to a large extent lose their integrative role when the rest of the neocortex is elimated."} {"id": "PMID:1274451", "title": "[The role of trace excitatory processes in the formation of conditioned reflexes to time].", "content": "I. P. Pavlov's hypothesis on the role of trace excitation in conditioning to time was verified by mathematical methods proceeding from experimental data on elaborating in rabbits a motor alimentary conditioned reflex to a four-minute interval of time. A connection has been established between the experimental characteristics of formation of a reflex to time and some parameters of the presumed dynamics of trace excitation. The analysis helped to establish the shortest and longest intervals to which a reflex to time can be elaborated by the mechanism of trace reflex, as well as the optimal interval to which it is elaborated more easily. The experimental results so obtained are a significant corroboration to the correctness of the Pavlov hypothesis.", "contents": "[The role of trace excitatory processes in the formation of conditioned reflexes to time]. I. P. Pavlov's hypothesis on the role of trace excitation in conditioning to time was verified by mathematical methods proceeding from experimental data on elaborating in rabbits a motor alimentary conditioned reflex to a four-minute interval of time. A connection has been established between the experimental characteristics of formation of a reflex to time and some parameters of the presumed dynamics of trace excitation. The analysis helped to establish the shortest and longest intervals to which a reflex to time can be elaborated by the mechanism of trace reflex, as well as the optimal interval to which it is elaborated more easily. The experimental results so obtained are a significant corroboration to the correctness of the Pavlov hypothesis."} {"id": "PMID:1274455", "title": "[The relationship between a conditioned slow negative potential and focused attention].", "content": "A conditioned slow negative vertex potential (CSNP) was studied in the interval between two stimuli: anticipatory and trigger, under different experimental conditions, namely; in response to a trigger stimulus the subject was to press an operating key; or to memorize the number of trigger stimuli; or to respond to the trigger stimulus by pressing the key and memorizing the number of anticipatory stimuli. A sound, geomatrical figures and separate words flashing up on a screen were used as stimuli. All of them were presented both as anticipatory and trigger signals. If a sound was used as an anticipatory stimulus, and a word as trigger one, the recorded CSNP was at its maximum in the case of a simple motor reaction, and at its lowest during retention. When the stimuli interchanged, was drawn to the anticipatory verbal stimulus, the CSNP amplitude diminished and the latency became shorter. The dependence of SCNP parameters on the subject's attention drawn to the anticipatory resp. trigger stimuli is discussed.", "contents": "[The relationship between a conditioned slow negative potential and focused attention]. A conditioned slow negative vertex potential (CSNP) was studied in the interval between two stimuli: anticipatory and trigger, under different experimental conditions, namely; in response to a trigger stimulus the subject was to press an operating key; or to memorize the number of trigger stimuli; or to respond to the trigger stimulus by pressing the key and memorizing the number of anticipatory stimuli. A sound, geomatrical figures and separate words flashing up on a screen were used as stimuli. All of them were presented both as anticipatory and trigger signals. If a sound was used as an anticipatory stimulus, and a word as trigger one, the recorded CSNP was at its maximum in the case of a simple motor reaction, and at its lowest during retention. When the stimuli interchanged, was drawn to the anticipatory verbal stimulus, the CSNP amplitude diminished and the latency became shorter. The dependence of SCNP parameters on the subject's attention drawn to the anticipatory resp. trigger stimuli is discussed."} {"id": "PMID:1274452", "title": "[EEG-correlates of alimentary behavior in rabbits with different levels of hunger and satiety].", "content": "The electrical activity of the rabbit brain at different stages of hunger and satiation was correlated with the animal's behavioral reactions. It has been found that alimentary reactions are attended with the appearance of complex high-amplitude and high-frequency electrical potentials in the lateral hypothalamic area, which increased with the longer duration of the animal's hunger, as well as during search, in response to natural and conditioned alimentary stimuli, and when feeding. As satiation sets in, they fade and disappear after food refusal. It is assumed that this form of activity is an EEG expression of alimentary motivational excitation. Its constituent rhythms reflect the different components of alimentary excitation.", "contents": "[EEG-correlates of alimentary behavior in rabbits with different levels of hunger and satiety]. The electrical activity of the rabbit brain at different stages of hunger and satiation was correlated with the animal's behavioral reactions. It has been found that alimentary reactions are attended with the appearance of complex high-amplitude and high-frequency electrical potentials in the lateral hypothalamic area, which increased with the longer duration of the animal's hunger, as well as during search, in response to natural and conditioned alimentary stimuli, and when feeding. As satiation sets in, they fade and disappear after food refusal. It is assumed that this form of activity is an EEG expression of alimentary motivational excitation. Its constituent rhythms reflect the different components of alimentary excitation."} {"id": "PMID:1274457", "title": "[The influence of learning on the \"setting\" of the spinal apparatus of reciprocal inhibition prior to voluntary motion].", "content": "The subjects performed daily for nine days from 200 to 250 single movements, namely a rapid dorsal flexion of the foot. Recording of the EMG of antagonist muscles and testing by the single and paired H-reflexes method has revealed three phenomena of learning: greater ratio of electrical activity (EA) of antagonist muscles owing to the enhanced agonist's EA; stronger reciprocal inhibition of the antagonist motoneurone nucleus at the beginning of the movement; enhanced supraspinal \"tuning\" of the spinal apparatus of the antagonist reciprocal inhibition before the beginning of the movement. It is suggested that the third phenomenon of learning underlies two phenomena.", "contents": "[The influence of learning on the \"setting\" of the spinal apparatus of reciprocal inhibition prior to voluntary motion]. The subjects performed daily for nine days from 200 to 250 single movements, namely a rapid dorsal flexion of the foot. Recording of the EMG of antagonist muscles and testing by the single and paired H-reflexes method has revealed three phenomena of learning: greater ratio of electrical activity (EA) of antagonist muscles owing to the enhanced agonist's EA; stronger reciprocal inhibition of the antagonist motoneurone nucleus at the beginning of the movement; enhanced supraspinal \"tuning\" of the spinal apparatus of the antagonist reciprocal inhibition before the beginning of the movement. It is suggested that the third phenomenon of learning underlies two phenomena."} {"id": "PMID:1274456", "title": "[Autonomic components of voluntary responses in children of different ages].", "content": "The formation of a complex of vegetative-somatic components of constructive activity (assembling figures out of mosaic chips) was analysed in children in the ontogenetic aspect during elaboration of a dynamic stereotype to direct stimuli (with presentation of samples) and during instantaneous formation of voluntary reactions to stimuli of a mainly second signal nature (without presentation of samples). The complex of effector vegetative-somatic components became more complicate and elaborate in the course of the child's growth, beginning with areflexia and disintegration in children of the younger groups (aged from two to three years) and up to correlated synchronous reflex changes of these components in children of the older group (six to seven years old).", "contents": "[Autonomic components of voluntary responses in children of different ages]. The formation of a complex of vegetative-somatic components of constructive activity (assembling figures out of mosaic chips) was analysed in children in the ontogenetic aspect during elaboration of a dynamic stereotype to direct stimuli (with presentation of samples) and during instantaneous formation of voluntary reactions to stimuli of a mainly second signal nature (without presentation of samples). The complex of effector vegetative-somatic components became more complicate and elaborate in the course of the child's growth, beginning with areflexia and disintegration in children of the younger groups (aged from two to three years) and up to correlated synchronous reflex changes of these components in children of the older group (six to seven years old)."} {"id": "PMID:1274458", "title": "[Dynamics of visual association formation in man].", "content": "The subjects were asked to memorize four combinations of paired visual stimuli on an illuminated tableau. The test-signal, a single flash on the tableau, was presented after the signal pair and could coincide either with the second component of the association or with the elements not involved in this particular association. After presentation of the test signal, the subject had to press the key as quickly as possible and then point to the pair on the tableau, associated with the signal pair (the second component of the association). The changes occuring in the structure of the association were evaluated by the changes of reaction time (rt) to the test-signal and the RT variability. Differences have been revealed between the RT dynamics and variabilities, which characterize the functional state of the elements activated during the achievement of the association and those not participating in the given association. During stabilization of the visual association, oppositely directed tendencies of RT changes and variabilities were observed.", "contents": "[Dynamics of visual association formation in man]. The subjects were asked to memorize four combinations of paired visual stimuli on an illuminated tableau. The test-signal, a single flash on the tableau, was presented after the signal pair and could coincide either with the second component of the association or with the elements not involved in this particular association. After presentation of the test signal, the subject had to press the key as quickly as possible and then point to the pair on the tableau, associated with the signal pair (the second component of the association). The changes occuring in the structure of the association were evaluated by the changes of reaction time (rt) to the test-signal and the RT variability. Differences have been revealed between the RT dynamics and variabilities, which characterize the functional state of the elements activated during the achievement of the association and those not participating in the given association. During stabilization of the visual association, oppositely directed tendencies of RT changes and variabilities were observed."} {"id": "PMID:1274460", "title": "[Dynamics of evoked potentials in cortical projection structures during a retarded instrumental defense reflex in dogs].", "content": "Evoked potentials (EP) in the somatosensory and auditory cortical areas were studied in four dogs against the background of a retarded defensive instrumental conditioned reflex to clicks. Four phases of the reflex were singled out by the changes in the structure of EP late components (LC) in the two projection zones. The most complex LC changes in the form of intensified negative components and the appearance of additional negative LC are recorded in response to the first click of the series and to the one followed by the conditioned motor reaction (CMR). Against the background of CMR delay, the EPs increased, while during the CMR, they decreased, owing to the diminished negative components, while the positive components were preserved and sometimes intensified. An assumption has been made that cortical projection structures of paired stimuli function in one and the same regime.", "contents": "[Dynamics of evoked potentials in cortical projection structures during a retarded instrumental defense reflex in dogs]. Evoked potentials (EP) in the somatosensory and auditory cortical areas were studied in four dogs against the background of a retarded defensive instrumental conditioned reflex to clicks. Four phases of the reflex were singled out by the changes in the structure of EP late components (LC) in the two projection zones. The most complex LC changes in the form of intensified negative components and the appearance of additional negative LC are recorded in response to the first click of the series and to the one followed by the conditioned motor reaction (CMR). Against the background of CMR delay, the EPs increased, while during the CMR, they decreased, owing to the diminished negative components, while the positive components were preserved and sometimes intensified. An assumption has been made that cortical projection structures of paired stimuli function in one and the same regime."} {"id": "PMID:1274459", "title": "[The capacity of dogs to solve problems by operating with the empirical dimensions of figures].", "content": "An investigation was made into the dogs capacity for operating with empirical dimensions of figures, i.e. the animal's capacity for solving problems based on the fact that out of two figures a volumetric bait can be placed only in a volumetric figure and not in a flat one. In experiments using two methods (single and multiple presentations of figures, each time of a new pair), the dogs were incapable of solving the problems. They were able, however, to elaborate in the course of learning a visual differentiation of a volumetric figure from a flat one, which implies the formation of a generalization of the volume cue as the only invariant in all the pairs of figures. The investigation into operation with empirical dimensions of figures as one of the objective parameters in estimating elementary reasoning activity of animals indicates that by this criterion dogs range in the philogenetic series by far lower than the previously studied marmoset monkeys and dolphins.", "contents": "[The capacity of dogs to solve problems by operating with the empirical dimensions of figures]. An investigation was made into the dogs capacity for operating with empirical dimensions of figures, i.e. the animal's capacity for solving problems based on the fact that out of two figures a volumetric bait can be placed only in a volumetric figure and not in a flat one. In experiments using two methods (single and multiple presentations of figures, each time of a new pair), the dogs were incapable of solving the problems. They were able, however, to elaborate in the course of learning a visual differentiation of a volumetric figure from a flat one, which implies the formation of a generalization of the volume cue as the only invariant in all the pairs of figures. The investigation into operation with empirical dimensions of figures as one of the objective parameters in estimating elementary reasoning activity of animals indicates that by this criterion dogs range in the philogenetic series by far lower than the previously studied marmoset monkeys and dolphins."} {"id": "PMID:1274461", "title": "[Dynamics of evoked potentials in the auditory zone of the dog cerebral cortex following extirpation of the medial geniculate bodies during formation of goal-directed behavior].", "content": "Integrative processes in the auditory cortical zone were studied in three dogs by EEG and EP parameters during the formation of a defensive reaction to clicks (four clicks, two per second) after the extirpation of the medial geniculate bodies. In the operated animals information is transmitted to the cortical end of the auditory analyser by compensatory paths with a larger number of relays. In the auditory cortex EPs are recorded with a longer latency (12 to 16 msec), and the duration of the negative EP component is increased (up to 40 msec). It is split mainly on the ascending front. The cortical end of the analyser participates in the formation of processes of afferent synthesis. In the active period of reflex elaboration the inflow of information increases: the EP amplitude and the duration of its main negative component become greater (up to 45-55 msec), as well as the splits on its fronts. In the course of preparing for a decision, before the achievement of the conditioned reaction, a \"double EP\" appears, which is due to enhanced reverberation of excitations in the compensatory paths.", "contents": "[Dynamics of evoked potentials in the auditory zone of the dog cerebral cortex following extirpation of the medial geniculate bodies during formation of goal-directed behavior]. Integrative processes in the auditory cortical zone were studied in three dogs by EEG and EP parameters during the formation of a defensive reaction to clicks (four clicks, two per second) after the extirpation of the medial geniculate bodies. In the operated animals information is transmitted to the cortical end of the auditory analyser by compensatory paths with a larger number of relays. In the auditory cortex EPs are recorded with a longer latency (12 to 16 msec), and the duration of the negative EP component is increased (up to 40 msec). It is split mainly on the ascending front. The cortical end of the analyser participates in the formation of processes of afferent synthesis. In the active period of reflex elaboration the inflow of information increases: the EP amplitude and the duration of its main negative component become greater (up to 45-55 msec), as well as the splits on its fronts. In the course of preparing for a decision, before the achievement of the conditioned reaction, a \"double EP\" appears, which is due to enhanced reverberation of excitations in the compensatory paths."} {"id": "PMID:1274462", "title": "[Formation of temporary connections in dogs following destruction of the amygdaloid complex, head of the caudate nucleus and orbital cortex].", "content": "Ablation of the orbital cortical zones in dogs after ablation of the basolateral part of the amygdala and the caudate nucleus head considerably impeded the elaboration of secretory conditioned alimentary reflexes, without affecting the rate of elaboration of simple instrumental food-procuring reaction. The dogs lost however the capacity to differentiate non-reinforced stimuli from reinforced ones, which was revealed in both secretory and instrumental reactions.", "contents": "[Formation of temporary connections in dogs following destruction of the amygdaloid complex, head of the caudate nucleus and orbital cortex]. Ablation of the orbital cortical zones in dogs after ablation of the basolateral part of the amygdala and the caudate nucleus head considerably impeded the elaboration of secretory conditioned alimentary reflexes, without affecting the rate of elaboration of simple instrumental food-procuring reaction. The dogs lost however the capacity to differentiate non-reinforced stimuli from reinforced ones, which was revealed in both secretory and instrumental reactions."} {"id": "PMID:1274463", "title": "[The effect of an extra-stimulus on successive inhibition following differentiations].", "content": "The influence of a foreign stimulus on the aftereffect of inhibitory stimuli was studied in experiments on dogs with salivary conditioned reflexes. The dynamics of temperature changes in the parotid salivary gland was used as an indicator since the action of a differentiation stimulus was accompanied by a drop in its temperature; each differentiation, whether rough, medium or fine--had its own limit of the gland's temperature drop during intensification of differentiation inhibition. It has been found that the dynamics of the gland temperature changes in the trace pauses and in response to a foreign stimulus depends on the modality of the stimulus, the duration of its action in the experiment, the typological properties of the animal's nervous system and the fineness of differentiation.", "contents": "[The effect of an extra-stimulus on successive inhibition following differentiations]. The influence of a foreign stimulus on the aftereffect of inhibitory stimuli was studied in experiments on dogs with salivary conditioned reflexes. The dynamics of temperature changes in the parotid salivary gland was used as an indicator since the action of a differentiation stimulus was accompanied by a drop in its temperature; each differentiation, whether rough, medium or fine--had its own limit of the gland's temperature drop during intensification of differentiation inhibition. It has been found that the dynamics of the gland temperature changes in the trace pauses and in response to a foreign stimulus depends on the modality of the stimulus, the duration of its action in the experiment, the typological properties of the animal's nervous system and the fineness of differentiation."} {"id": "PMID:1274464", "title": "[The role of the pallidum in regulating cortical activity].", "content": "Bilateral ablation of the pallidum halves the duration of extinction of conditioned motor food reflexes and contributes to 30 to 50% extinction of the electro-defensive reflexes. Pallidum functional depression by potassium chloride or novacaine leads to a temporary total depression of conditioned motor food reflexes. Depending on the frequency of pallidum stimulation, synchronization or desynchronization of the cortical bioelectrical activity is observed. Ablation of the pallidum in anaesthetized cats results in a high amplitude and low-frequency cortical activity. Injection of large doses of potassium chloride into the pallidum results in a forced running forward which lasts 30 to 40 min. The pallidum is considreed as a structure controlling the cortex activity, which takes part in the mechanisms of sensory information processes in the course of adaptive behaviour.", "contents": "[The role of the pallidum in regulating cortical activity]. Bilateral ablation of the pallidum halves the duration of extinction of conditioned motor food reflexes and contributes to 30 to 50% extinction of the electro-defensive reflexes. Pallidum functional depression by potassium chloride or novacaine leads to a temporary total depression of conditioned motor food reflexes. Depending on the frequency of pallidum stimulation, synchronization or desynchronization of the cortical bioelectrical activity is observed. Ablation of the pallidum in anaesthetized cats results in a high amplitude and low-frequency cortical activity. Injection of large doses of potassium chloride into the pallidum results in a forced running forward which lasts 30 to 40 min. The pallidum is considreed as a structure controlling the cortex activity, which takes part in the mechanisms of sensory information processes in the course of adaptive behaviour."} {"id": "PMID:1274465", "title": "[The role of the medial geniculate bodies in analyzing sounds].", "content": "Elaboration and manifestation of motor alimentary conditioned reflexes were studied after a lesion of medial geniculate bodies (MGB) in adult cats. No substantial disturbance were recorded of the capacity for pitch analysis. In the case of more extensive MGB lesions, there were some difficulties in the elaboration of tone differentiations but not in their achievement. Additional temporo-parietal cortical ablation drastically reduced the animals' capacity for anlysing sound frequencies and more profoundly disturbed their capacity for inhibitory reactions.", "contents": "[The role of the medial geniculate bodies in analyzing sounds]. Elaboration and manifestation of motor alimentary conditioned reflexes were studied after a lesion of medial geniculate bodies (MGB) in adult cats. No substantial disturbance were recorded of the capacity for pitch analysis. In the case of more extensive MGB lesions, there were some difficulties in the elaboration of tone differentiations but not in their achievement. Additional temporo-parietal cortical ablation drastically reduced the animals' capacity for anlysing sound frequencies and more profoundly disturbed their capacity for inhibitory reactions."} {"id": "PMID:1274466", "title": "[The effect of ablation of the caudate nucleus on the alimentary zone of the lateral hypothalamus].", "content": "A conditioned food-procuring reaction previously elaborated to an acoustic stimulus was reproduced in chronic experiments on six cats by means of direct electrical stimulation of the posterior parts of the lateral hypothalamus. Folloiwng extensive bilateral electrolytic ablation of the caudate nucleus, conditioned food-procuring reaction to the stimulation of the hypothalamus could not be reproduced for 40 to 70 days. The conditioned foor-procuring reflex to the acoustic stimulus disappeared for 14 to 30 days to be subsequently spontaneously restored. After caudatotomy, a diminution of the average amplitude of background oscillations and of evoked potentials to acoustic stimuli was recorced in the examined zones of the lateral hypothalamus. The part played by the caudate nucleus in the processes of alimentary behaviour activation is discussed.", "contents": "[The effect of ablation of the caudate nucleus on the alimentary zone of the lateral hypothalamus]. A conditioned food-procuring reaction previously elaborated to an acoustic stimulus was reproduced in chronic experiments on six cats by means of direct electrical stimulation of the posterior parts of the lateral hypothalamus. Folloiwng extensive bilateral electrolytic ablation of the caudate nucleus, conditioned food-procuring reaction to the stimulation of the hypothalamus could not be reproduced for 40 to 70 days. The conditioned foor-procuring reflex to the acoustic stimulus disappeared for 14 to 30 days to be subsequently spontaneously restored. After caudatotomy, a diminution of the average amplitude of background oscillations and of evoked potentials to acoustic stimuli was recorced in the examined zones of the lateral hypothalamus. The part played by the caudate nucleus in the processes of alimentary behaviour activation is discussed."} {"id": "PMID:1274467", "title": "[Conditioned responses to time of hypothalamic neurons. The ventromedial nucleus].", "content": "Conditioned reactions to the time of regularly (every 30 sec.) presented pairings of an acoustic and an electrical cutaneous stimuli were studied in neurones of the hypothalamic ventromedial nucleus in an alert rabbit. Conditioned reactions of an inhibitory (81%) and activating (19%) types were elaborated in 27 out of 63 units (43%). They were significantly reproduced at six to nine omissions of stimulations at the stage of the 50th to 70th pairings. The maximum manifestation of trace processes coincides with the initial formation of a vegetative (electrocardiogram) component of the behavioral conditioned reflex to time. Significant correlation has been shown between the frequency of spikes in the pairings and their omissions, and the corresponding changes in heart rate at the same temporal intervals. This testifies to the involvement of the ventromedial nucleus structures in the formation of the vegetative component of the behavioral conditioned reflex to time. Common characteristics and peculiarities of conditioned reactions to time have been revealed in units of the hypothalamic ventromedial and perifornical nuclei in accordance with morpho-functional properties of the examined structures.", "contents": "[Conditioned responses to time of hypothalamic neurons. The ventromedial nucleus]. Conditioned reactions to the time of regularly (every 30 sec.) presented pairings of an acoustic and an electrical cutaneous stimuli were studied in neurones of the hypothalamic ventromedial nucleus in an alert rabbit. Conditioned reactions of an inhibitory (81%) and activating (19%) types were elaborated in 27 out of 63 units (43%). They were significantly reproduced at six to nine omissions of stimulations at the stage of the 50th to 70th pairings. The maximum manifestation of trace processes coincides with the initial formation of a vegetative (electrocardiogram) component of the behavioral conditioned reflex to time. Significant correlation has been shown between the frequency of spikes in the pairings and their omissions, and the corresponding changes in heart rate at the same temporal intervals. This testifies to the involvement of the ventromedial nucleus structures in the formation of the vegetative component of the behavioral conditioned reflex to time. Common characteristics and peculiarities of conditioned reactions to time have been revealed in units of the hypothalamic ventromedial and perifornical nuclei in accordance with morpho-functional properties of the examined structures."} {"id": "PMID:1274470", "title": "[Post-tetanic strengthening of evoked electrical responses of the sensomotor cortex].", "content": "A study has been made of the posttetanic potentiation of evoked potentials (PTP EP) in the sensorimotor cortex, appearing in response to VPL stimulation. A distinct PTP EP of the cortical surface has been found as well as considerable differences in its intensity recorded at different portions of deep cortical layers (700 to 1600 mu). Suggestions were made regarding the origin of the phenomena observed.", "contents": "[Post-tetanic strengthening of evoked electrical responses of the sensomotor cortex]. A study has been made of the posttetanic potentiation of evoked potentials (PTP EP) in the sensorimotor cortex, appearing in response to VPL stimulation. A distinct PTP EP of the cortical surface has been found as well as considerable differences in its intensity recorded at different portions of deep cortical layers (700 to 1600 mu). Suggestions were made regarding the origin of the phenomena observed."} {"id": "PMID:1274468", "title": "[Neurochemical mechanisms of the septum in food getting conditioned responses in rats].", "content": "The influence of microinjections of monoamines and of glutamic acid into the lateral zone of the septum on a food-procuring conditioned reaction was studied in experiments on rats. Dopamine does not change, while noradrenaline, serotonin and glutamic acid increase the magnitude and number of conditioned food-procuring movements and substantially lengthen the reflex latency. The effects of serotonin are achieved through D-serotonin-, and of noradrenaline, through L-adrenoreactive structures of the neuronal systems of the septum. The influence of glutamic acid on the rat food-procuring conditioned reactions is not linked with the action on the serotonin- or adrenoreactive structures of the septum neuronal systems.", "contents": "[Neurochemical mechanisms of the septum in food getting conditioned responses in rats]. The influence of microinjections of monoamines and of glutamic acid into the lateral zone of the septum on a food-procuring conditioned reaction was studied in experiments on rats. Dopamine does not change, while noradrenaline, serotonin and glutamic acid increase the magnitude and number of conditioned food-procuring movements and substantially lengthen the reflex latency. The effects of serotonin are achieved through D-serotonin-, and of noradrenaline, through L-adrenoreactive structures of the neuronal systems of the septum. The influence of glutamic acid on the rat food-procuring conditioned reactions is not linked with the action on the serotonin- or adrenoreactive structures of the septum neuronal systems."} {"id": "PMID:1274471", "title": "[Functional maturation of the cat visual cortex during prenatal ontogenesis].", "content": "Development of the perceiving function of the visual cortex was studied on the foeti of cats in the second stage of antenatal development with intact placental blood circulation. It has been found that functional maturing of the cortical end of the visual analyser starts at the beginning of the second half of antenatal life. At this period EPs to stimulation of the optic nerve are recorded throughout the dorsal cortex of the contralateral hemisphere. At first they appear as slow three-phase (positive-negative-positive) oscillations of a small amplitude. As the foetus develops, the EP amplitude increases, and the EP configuration in the striate zone of the cortex becomes complex. Two weaks before birth, a short-latency negative wave appears against the background of the primary positive oscillation. In the last week of antenatal development of the foeti and in the first few days of the kittens life, EPs are represented in the specific zone of the visual cortex (g. lateralis) as two negative oscillations, and in the so-called associative zone (the middle part of the suprasylvian gyrus) by one long-latency high-amplitude negative oscillation which corresponds by latency to the second negative EP component in the striate cortex.", "contents": "[Functional maturation of the cat visual cortex during prenatal ontogenesis]. Development of the perceiving function of the visual cortex was studied on the foeti of cats in the second stage of antenatal development with intact placental blood circulation. It has been found that functional maturing of the cortical end of the visual analyser starts at the beginning of the second half of antenatal life. At this period EPs to stimulation of the optic nerve are recorded throughout the dorsal cortex of the contralateral hemisphere. At first they appear as slow three-phase (positive-negative-positive) oscillations of a small amplitude. As the foetus develops, the EP amplitude increases, and the EP configuration in the striate zone of the cortex becomes complex. Two weaks before birth, a short-latency negative wave appears against the background of the primary positive oscillation. In the last week of antenatal development of the foeti and in the first few days of the kittens life, EPs are represented in the specific zone of the visual cortex (g. lateralis) as two negative oscillations, and in the so-called associative zone (the middle part of the suprasylvian gyrus) by one long-latency high-amplitude negative oscillation which corresponds by latency to the second negative EP component in the striate cortex."} {"id": "PMID:1274469", "title": "[Changes in evoked potentials during systematic exposure to a series of similar signals with variable intersignal intervals].", "content": "Series of clicks, standard by the number of stimuli and greatly varying by the length of interstimuli intervals in each series, were systematically presented to dogs without reinforcement. Evoked potentiale (EP) in the cortical auditory zone were recorded. It has been found that a typical U-shaped distribution of amplitude values of averaged EP is elaborated in the series in the course of repeated presentations; a maximal amplitude is observed in response to the first and last clicks, and a minimal, in the middle of the series. Such a regularity was previously found for the action of standard series with a constant interstimuli interval. It is assumed that an estimation may take place in the dog CNS of the number of signals used in a series, whose mechanism is not necessarily based on the time factor. The ability to estimate the number of signals in the series may be regarded as an elementary model of counting in the dogs' CNS.", "contents": "[Changes in evoked potentials during systematic exposure to a series of similar signals with variable intersignal intervals]. Series of clicks, standard by the number of stimuli and greatly varying by the length of interstimuli intervals in each series, were systematically presented to dogs without reinforcement. Evoked potentiale (EP) in the cortical auditory zone were recorded. It has been found that a typical U-shaped distribution of amplitude values of averaged EP is elaborated in the series in the course of repeated presentations; a maximal amplitude is observed in response to the first and last clicks, and a minimal, in the middle of the series. Such a regularity was previously found for the action of standard series with a constant interstimuli interval. It is assumed that an estimation may take place in the dog CNS of the number of signals used in a series, whose mechanism is not necessarily based on the time factor. The ability to estimate the number of signals in the series may be regarded as an elementary model of counting in the dogs' CNS."} {"id": "PMID:1274472", "title": "[Functional heterogeneity of lateral geniculate body neurons in the rabbit].", "content": "Background and evoked activity of LGB units was studied on immobilized and anaesthetized rabbits. Two groups of projection units were revealed, differing by the level of background activity, latencies and mean frequency of discharges in responses to single photic flashes and to electrical stimulation of the optic nerve. It is assumed that these groups of units belong to the slowly and rapidly conducting paths of sensory information transmission in the visual projection system.", "contents": "[Functional heterogeneity of lateral geniculate body neurons in the rabbit]. Background and evoked activity of LGB units was studied on immobilized and anaesthetized rabbits. Two groups of projection units were revealed, differing by the level of background activity, latencies and mean frequency of discharges in responses to single photic flashes and to electrical stimulation of the optic nerve. It is assumed that these groups of units belong to the slowly and rapidly conducting paths of sensory information transmission in the visual projection system."} {"id": "PMID:1274473", "title": "[The character of changes in the background and superimposed rhythmics of cerebral biopotentials in rabbits exposed to a steady magnetic field of high intensity].", "content": "During a total action of a static magnetic field (SMF) of 1000--4000 Oe, high-amplitude synchronized discharges appear in the electrograms of the cortical and subcortical parts of the rabbit brain. An automatic frequency analysis exhibits increased bioelectrical activity in the range of 8 to 30 c/s with no substantial changes in slower rhythms. The effect increases as the field becomes stronger. A SMF of 1000 Oe tends to facilitate the photic driving which persists as an after-effect. In SMF of 3000 Oe the driving reaction is weakened; it is rapidly restored after cessation of the SMF action.", "contents": "[The character of changes in the background and superimposed rhythmics of cerebral biopotentials in rabbits exposed to a steady magnetic field of high intensity]. During a total action of a static magnetic field (SMF) of 1000--4000 Oe, high-amplitude synchronized discharges appear in the electrograms of the cortical and subcortical parts of the rabbit brain. An automatic frequency analysis exhibits increased bioelectrical activity in the range of 8 to 30 c/s with no substantial changes in slower rhythms. The effect increases as the field becomes stronger. A SMF of 1000 Oe tends to facilitate the photic driving which persists as an after-effect. In SMF of 3000 Oe the driving reaction is weakened; it is rapidly restored after cessation of the SMF action."} {"id": "PMID:1274480", "title": "Effects of food ecology on social play: a laboratory simulation.", "content": "A laboratory group of 8 squirrel monkeys was exposed to two experimental conditions in which food was made moderately and extremely difficult to obtain, compared with the free access conditions of baseline. Both experiments produced sharp decreased in the frequency of social play within 4 to 6 days. The stronger manipulation produced the more dramatic effect, reducing play to 1% of the baseline level (P less than .001). Neither experiment produced a total absence of play as was observed in a previous field study in southwestern Panama (Baldwin and Baldwin 1973, 1974) which suggests that the field study sampled conditions of even more severe and/or prolonged food deprivation. No pathological or dysfunctional consequences were observed in any of the circumstances where play was reduced to zero or near zero. The question is raised whether certain theories of play have overstated the case for the necessity of play experience in producing normal socialization in primates. Alternative hypotheses are presented concerning the factors that determine the frequency of play and the consequences of play versus no-play for socialization. After both experiments, the frequency of play rose to a level 50% higher than the average baseline levels of play. This \"rebound\" reached a peak 5 to 6 days after the termination of each experiment; and during the subsequent days the frequency of play declined to more normal levels. A reinforcement theory is presented as a possible explanation of the rebound effect.", "contents": "Effects of food ecology on social play: a laboratory simulation. A laboratory group of 8 squirrel monkeys was exposed to two experimental conditions in which food was made moderately and extremely difficult to obtain, compared with the free access conditions of baseline. Both experiments produced sharp decreased in the frequency of social play within 4 to 6 days. The stronger manipulation produced the more dramatic effect, reducing play to 1% of the baseline level (P less than .001). Neither experiment produced a total absence of play as was observed in a previous field study in southwestern Panama (Baldwin and Baldwin 1973, 1974) which suggests that the field study sampled conditions of even more severe and/or prolonged food deprivation. No pathological or dysfunctional consequences were observed in any of the circumstances where play was reduced to zero or near zero. The question is raised whether certain theories of play have overstated the case for the necessity of play experience in producing normal socialization in primates. Alternative hypotheses are presented concerning the factors that determine the frequency of play and the consequences of play versus no-play for socialization. After both experiments, the frequency of play rose to a level 50% higher than the average baseline levels of play. This \"rebound\" reached a peak 5 to 6 days after the termination of each experiment; and during the subsequent days the frequency of play declined to more normal levels. A reinforcement theory is presented as a possible explanation of the rebound effect."} {"id": "PMID:1274481", "title": "Songs, choruses and countersinging of Kloss' gibbons (Hylobates klossii) in Siberut Island, Indonesia.", "content": "This study evaluates the social spacing mechanism of song as it occurs in Kloss' gibbons. The study population included individuals in 13 family groups whose composition and territories were known (TENZA 1975) plus a number of others. Sonagrams illustrate individual and sexual differences in singing. Sex differences in chorusing, countersinging and other behavior related to song are described. Variations in singing or chorusing or both are related to season, time of day, sex, age, spatial factors and social factors. The adaptive functions of singing, countersinging and chorusing are discussed. It is concluded that: (1) Song is mainly for interterritorial communication between members of the same sex, (2) male-song probably also functions in mate attraction and (3) chorusing is primarily an adaptation reducing predation risk to singing gibbons.", "contents": "Songs, choruses and countersinging of Kloss' gibbons (Hylobates klossii) in Siberut Island, Indonesia. This study evaluates the social spacing mechanism of song as it occurs in Kloss' gibbons. The study population included individuals in 13 family groups whose composition and territories were known (TENZA 1975) plus a number of others. Sonagrams illustrate individual and sexual differences in singing. Sex differences in chorusing, countersinging and other behavior related to song are described. Variations in singing or chorusing or both are related to season, time of day, sex, age, spatial factors and social factors. The adaptive functions of singing, countersinging and chorusing are discussed. It is concluded that: (1) Song is mainly for interterritorial communication between members of the same sex, (2) male-song probably also functions in mate attraction and (3) chorusing is primarily an adaptation reducing predation risk to singing gibbons."} {"id": "PMID:1274485", "title": "[About a rare teratoma of the pineal region (author's transl)].", "content": "1. Report on a man aged 33 with a rare teratoma of the pineal region (adult teratoma with pinealoma-like parts) and 8 related cases of the literature. 2. The absence of the pinealis in our case and in 4 related cases of the literature is explained as a result of destruction of pinealis by the tumor. 3. The pinealis in our case cannot be considered as the origin of pinealoma-like part of the teratoma. The pinealoma-like part seems to have the same root as the teratoma. The argumentation of this opinion is the arrangement and the seize of pinealoma-like parts in the teratoma as well as the often shown proof of an unchanged pinealis and the observation of similar histological patterns in extracranial teratomas.", "contents": "[About a rare teratoma of the pineal region (author's transl)]. 1. Report on a man aged 33 with a rare teratoma of the pineal region (adult teratoma with pinealoma-like parts) and 8 related cases of the literature. 2. The absence of the pinealis in our case and in 4 related cases of the literature is explained as a result of destruction of pinealis by the tumor. 3. The pinealis in our case cannot be considered as the origin of pinealoma-like part of the teratoma. The pinealoma-like part seems to have the same root as the teratoma. The argumentation of this opinion is the arrangement and the seize of pinealoma-like parts in the teratoma as well as the often shown proof of an unchanged pinealis and the observation of similar histological patterns in extracranial teratomas."} {"id": "PMID:1274486", "title": "[Changes of the tuberculosis of the central nervous system since the introduction of prophylactic BCG vaccination and tuberculostatic therapy (author's transl)].", "content": "From 1924 to 1938, 9920 autopsies were carried out in our institute; from 1955 to 1969 there were 37 784 dissections. Among the former 132 cases of tuberculous meningitis (tb. m.) were observed (1.33%), among the latter there were only 74 (0.20%). This decrease in frequency to about 1/7 is statistically highly significant; by standardization to 0.62 it has come down to 0.20% but still remains significant. The marked predominance of tb. m. in males as compared to females (2:1) that was noted in former autopsies is no longer noticeable. With regard to age distribution, a statistically warrented decrease exists only for the age group from 0 to 9 years. From the mortality graph (the dying age being identical with that of affection before the era of chemotherapy) it can be seen that while the peak during childhood has now disappeared, it is only slightly demonstrable during early adult age (as a result of the retarded primary infection). The rise in the curve indicates the deteriorating prognosis with increasing age, with the peak between 60 and 70 years accounting for the importance of miliary tuberculosis of old age for tb. m. Due to therapeutic measures, there is now an increase in the number of chronic tb. m. cases which are productive in their histological picture. As previously, tb. m. at present develops in about half of the cases in the course of miliary tuberculosis. The frequency of early generalization has significantly decreased, while that of miliary tuberculosis of old age has increased. In our examination material tb. m. without further manifestations of tuberculosis has become provable only since the introduction of chemotherapy. Errors in clinical diagnoses have increased from 12.9 to 54%. The decrease of tuberculomata of the central nervous system from 0.17 to 0.013% is also statistically highly significant in our examination material. Apart from the change of the examination material, this decrease in frequency is largely due to prophylactic BCG vaccination and tuberculo-static therapy. Both of them have brought on the rapid advances in tuberculosis epidemiology that started with the turn of the century and resulted mainly in shifting tuberculous primary infection to higher ages and, at the same time, markedly reducing the contagion of tuberculosis.", "contents": "[Changes of the tuberculosis of the central nervous system since the introduction of prophylactic BCG vaccination and tuberculostatic therapy (author's transl)]. From 1924 to 1938, 9920 autopsies were carried out in our institute; from 1955 to 1969 there were 37 784 dissections. Among the former 132 cases of tuberculous meningitis (tb. m.) were observed (1.33%), among the latter there were only 74 (0.20%). This decrease in frequency to about 1/7 is statistically highly significant; by standardization to 0.62 it has come down to 0.20% but still remains significant. The marked predominance of tb. m. in males as compared to females (2:1) that was noted in former autopsies is no longer noticeable. With regard to age distribution, a statistically warrented decrease exists only for the age group from 0 to 9 years. From the mortality graph (the dying age being identical with that of affection before the era of chemotherapy) it can be seen that while the peak during childhood has now disappeared, it is only slightly demonstrable during early adult age (as a result of the retarded primary infection). The rise in the curve indicates the deteriorating prognosis with increasing age, with the peak between 60 and 70 years accounting for the importance of miliary tuberculosis of old age for tb. m. Due to therapeutic measures, there is now an increase in the number of chronic tb. m. cases which are productive in their histological picture. As previously, tb. m. at present develops in about half of the cases in the course of miliary tuberculosis. The frequency of early generalization has significantly decreased, while that of miliary tuberculosis of old age has increased. In our examination material tb. m. without further manifestations of tuberculosis has become provable only since the introduction of chemotherapy. Errors in clinical diagnoses have increased from 12.9 to 54%. The decrease of tuberculomata of the central nervous system from 0.17 to 0.013% is also statistically highly significant in our examination material. Apart from the change of the examination material, this decrease in frequency is largely due to prophylactic BCG vaccination and tuberculo-static therapy. Both of them have brought on the rapid advances in tuberculosis epidemiology that started with the turn of the century and resulted mainly in shifting tuberculous primary infection to higher ages and, at the same time, markedly reducing the contagion of tuberculosis."} {"id": "PMID:1274487", "title": "[Mesenchymal chondrosarcoma. Report of two extraskeletal cases (author's transl)].", "content": "After a thorough examination of the literature, two new cases of mesenchymal chondrosarcoma of extraskeletal soft tissues are reported. By means of clinical and pathological survey the distinguishing findings of typical and mesenchymal chondrosarcoma, their malignancy and the differences between the skeletal and extraskeletal form are described.", "contents": "[Mesenchymal chondrosarcoma. Report of two extraskeletal cases (author's transl)]. After a thorough examination of the literature, two new cases of mesenchymal chondrosarcoma of extraskeletal soft tissues are reported. By means of clinical and pathological survey the distinguishing findings of typical and mesenchymal chondrosarcoma, their malignancy and the differences between the skeletal and extraskeletal form are described."} {"id": "PMID:1274496", "title": "[Diagnosis of rubella by demonstrating rubella-specific 19 S and 7 S antibodies (author's transl)].", "content": "Identification and measurement of rubella antibody of 19 S (IgM) and 7 S (IgG) immunoglobulins by sucrose density gradient centrifugation and a modified hemagglutination-inhibition (HAI)-test is described. Human group 0 of red blood cells were employed after trypsination. The method proved to be highly reliable and sensitive for the rapid detection of rubella IgM antibody in routine research to make an accurate diagnosis of recent rubella infection. Sera from 185 pregnant women, 200 children suspect of congenital infection, 15 mothers of intrauterin infected children, and 32 cases of rubella vaccine-induced immunity control were studied. In postnatal rubella infections, specific IgM-antibody could be detected in all sera after the onset of the rash up to eight or ten weeks after infection. From March 1973 until September 1974 laboratory diagnosis confirmed 30 of 185 pregnant women to have been recently infected with rubella. In less than 3% (4 cases) the results could not confirm or exclude a recent history of rubella. Among 200 children with congenital defects or some irregular development, specific IgM antibody was detected in 36 cases. The diagnosis of congenital rubella was confirmed or detected in the first months of life. One of the infected children was well at birth but later developed mental retardation and hearing loss, and some others showed only minor defects. In some children rubell IgM antibody persisted 5-14 months. IgM rubella antibody was not found in the sera of 15 mothers from children with intrauterine infection confirmed by IgM antibody demonstration. Post-vaccination-tests showed serum IgM and IgG immunoglobulin-responses to be similar to the natural rubella-virus-infection. Maximal titers of both immunoglobulin-fractions were but four-fold lower after vaccination (28 of 32 tested cases). The described method is able to verify the time of infection by testing a single serum. The HAI-test of the 12 fractions collected from each serum after density-gradient centrifugation shows a typical titer-profil for every time of immunization status: beginning with traces of IgM-antibody - when the HAI-test of the uncentrifugated serum may be less than 1:10 - until 10 weeks after infection when only IgG-antibody will be detectable. The greatest amount of IgM-antibody is found in the 2. to 4. week after the rash.", "contents": "[Diagnosis of rubella by demonstrating rubella-specific 19 S and 7 S antibodies (author's transl)]. Identification and measurement of rubella antibody of 19 S (IgM) and 7 S (IgG) immunoglobulins by sucrose density gradient centrifugation and a modified hemagglutination-inhibition (HAI)-test is described. Human group 0 of red blood cells were employed after trypsination. The method proved to be highly reliable and sensitive for the rapid detection of rubella IgM antibody in routine research to make an accurate diagnosis of recent rubella infection. Sera from 185 pregnant women, 200 children suspect of congenital infection, 15 mothers of intrauterin infected children, and 32 cases of rubella vaccine-induced immunity control were studied. In postnatal rubella infections, specific IgM-antibody could be detected in all sera after the onset of the rash up to eight or ten weeks after infection. From March 1973 until September 1974 laboratory diagnosis confirmed 30 of 185 pregnant women to have been recently infected with rubella. In less than 3% (4 cases) the results could not confirm or exclude a recent history of rubella. Among 200 children with congenital defects or some irregular development, specific IgM antibody was detected in 36 cases. The diagnosis of congenital rubella was confirmed or detected in the first months of life. One of the infected children was well at birth but later developed mental retardation and hearing loss, and some others showed only minor defects. In some children rubell IgM antibody persisted 5-14 months. IgM rubella antibody was not found in the sera of 15 mothers from children with intrauterine infection confirmed by IgM antibody demonstration. Post-vaccination-tests showed serum IgM and IgG immunoglobulin-responses to be similar to the natural rubella-virus-infection. Maximal titers of both immunoglobulin-fractions were but four-fold lower after vaccination (28 of 32 tested cases). The described method is able to verify the time of infection by testing a single serum. The HAI-test of the 12 fractions collected from each serum after density-gradient centrifugation shows a typical titer-profil for every time of immunization status: beginning with traces of IgM-antibody - when the HAI-test of the uncentrifugated serum may be less than 1:10 - until 10 weeks after infection when only IgG-antibody will be detectable. The greatest amount of IgM-antibody is found in the 2. to 4. week after the rash."} {"id": "PMID:1274497", "title": "[Mixed infections by hemolyzing streptococci in clinical material (author's transl)].", "content": "The distribution of serogroups among 156 strains of beta-hemolyzing streptococci from clinical material was as follows: A - 64.1%, B - 3.2%, C - 11.5%, D - 0.6%, F- 6.4%, G - 14.1% (Table 1). Serogroup A was found in pus specimens in 84%, in throat swabs in 67%, and in sputum specimens (x2 greater than 6.64) in only 23% of strains; among clinical diagnoses (Table 2), distribution of this group was as follows: scarlet fever 100%, infected wounds 83%, and otorhinolaryngological diseases less than 70% of strains. From 54% of specimens received, other organisms were isolated in addition to beta-hemolyzing streptococci, In Table 3, the distribution of serogroups (x2 greater than 1) in cases of single and mixed infections is shown for the most frequent types of material received. Combinations of the individual serogroups with concomitant bacteria, above all Staphylococcus aureus, a number of enterobacteria, and Haemophilus influenzae can be seen from Table 4. Staph. aureus was found preferentially in combination with group A streptococci (x2 greater then 6.64). The proportion of mixed infections among specimens of the most important types of material was varying (Table 5): 82% of sputum specimens, 46%of throat swabs, and 39% of pus specimens. As concomitant organisms, especially Haem. influenzae, Staph. aureus (in throat swabs and pus specimens), and enterobacteria were found. With scarlet fever, Staph. aureus was present in as much as 60% of all cases. Ampicillin-resistant strains were isolated among the various concomitant organisms from 22% of all materials and 45% of all sputum specimens.", "contents": "[Mixed infections by hemolyzing streptococci in clinical material (author's transl)]. The distribution of serogroups among 156 strains of beta-hemolyzing streptococci from clinical material was as follows: A - 64.1%, B - 3.2%, C - 11.5%, D - 0.6%, F- 6.4%, G - 14.1% (Table 1). Serogroup A was found in pus specimens in 84%, in throat swabs in 67%, and in sputum specimens (x2 greater than 6.64) in only 23% of strains; among clinical diagnoses (Table 2), distribution of this group was as follows: scarlet fever 100%, infected wounds 83%, and otorhinolaryngological diseases less than 70% of strains. From 54% of specimens received, other organisms were isolated in addition to beta-hemolyzing streptococci, In Table 3, the distribution of serogroups (x2 greater than 1) in cases of single and mixed infections is shown for the most frequent types of material received. Combinations of the individual serogroups with concomitant bacteria, above all Staphylococcus aureus, a number of enterobacteria, and Haemophilus influenzae can be seen from Table 4. Staph. aureus was found preferentially in combination with group A streptococci (x2 greater then 6.64). The proportion of mixed infections among specimens of the most important types of material was varying (Table 5): 82% of sputum specimens, 46%of throat swabs, and 39% of pus specimens. As concomitant organisms, especially Haem. influenzae, Staph. aureus (in throat swabs and pus specimens), and enterobacteria were found. With scarlet fever, Staph. aureus was present in as much as 60% of all cases. Ampicillin-resistant strains were isolated among the various concomitant organisms from 22% of all materials and 45% of all sputum specimens."} {"id": "PMID:1274498", "title": "Morphological, cultural and biochemical characteristics of Vibrio parahaemolyticus, isolated in Romania from acute gastro-enteritis.", "content": "Out of 399 human faeces examined during the first eight months (1975) for the presence of NCV vibrios, one vibrio parahaemolyticus strains has been isolated from a man with acute gastro-enteritis (gastric and abdominal pains, nausea, diarrhoea, headache, general weakness), after having a meal with salted caviar. The strain belongs to Heiberg's group VII and Sakazaki's subgroup I. The virulence tested on chick embryo is 3 times higher (LD50 = 14 germs) if compared with the virulence of V. parahaemolyticus control strain (Sakazaki's strains). First isolation in Romania from a human stool (patient with acute gastro-enteritis).", "contents": "Morphological, cultural and biochemical characteristics of Vibrio parahaemolyticus, isolated in Romania from acute gastro-enteritis. Out of 399 human faeces examined during the first eight months (1975) for the presence of NCV vibrios, one vibrio parahaemolyticus strains has been isolated from a man with acute gastro-enteritis (gastric and abdominal pains, nausea, diarrhoea, headache, general weakness), after having a meal with salted caviar. The strain belongs to Heiberg's group VII and Sakazaki's subgroup I. The virulence tested on chick embryo is 3 times higher (LD50 = 14 germs) if compared with the virulence of V. parahaemolyticus control strain (Sakazaki's strains). First isolation in Romania from a human stool (patient with acute gastro-enteritis)."} {"id": "PMID:1274499", "title": "[The genus Brucella, its nomenclature and taxonomic specificity (author's transl)].", "content": "The author suggest to change the nomenclature of Genus-Brucella as follows: Brucella melitensis, B. bovis, B. suis, B. canis, B. neotomae, B. rangiferi, B. murium. In the new edition of \"Bergey's Manual\" it is suggested to quote some highly taxonomic specific substances, berucellaphages, Brucelline, protective substance, precipitinogen, and toxins (Endotoxin, Lipoprotein).", "contents": "[The genus Brucella, its nomenclature and taxonomic specificity (author's transl)]. The author suggest to change the nomenclature of Genus-Brucella as follows: Brucella melitensis, B. bovis, B. suis, B. canis, B. neotomae, B. rangiferi, B. murium. In the new edition of \"Bergey's Manual\" it is suggested to quote some highly taxonomic specific substances, berucellaphages, Brucelline, protective substance, precipitinogen, and toxins (Endotoxin, Lipoprotein)."} {"id": "PMID:1274500", "title": "[Differentiation of swine-Mycoplasma by latex-agglutination (author's transl)].", "content": "The strains of Mycoplasma were grown in Shittlestone medium for 3-5 days. After centrifugation and washing, the mycoplasm were freeze-dried and stored at -20 degrees C. From this stock material immune sera and antigens were prepared. The immune sera were prepared by immunization of rabbits with a suspension of mycoplasma (2,2 mg dry weight per ml) and complete Freund's adjuvant. For the first immunication, 6.6 mg of antigen were injected into rabbits at different sites. 3 weeks later the second immunization followed by the intramuscular route (4.4 mg of antigen). The third and fourth immunizations were identical to the second one. Antiserum was obtained as usual. In order to avoid unspecific reactions in the latex agglutination, 1 ml of antiserum was added for absorption to 200 mg of freeze-dried sterile Whittlestone medium over 2 days at 4 degrees C. Antigen was prepared by ultrasonic disruption of mycoplasma (20 mg dry weight/ml physiological saline) and centrifugation 17300 X g, 30 min). The supernatant was used as antigen. The latex agglutination was performed in 0.1 M borate buffer pH 8,2. For preparation of the latex antigen compound 0.2 ml of a latex suspension (diluted 5 fold with water) were moxed with 0.5 ml of an antigen suspension (diluted 16 fold with buffer). After 10 min at room temperature, 4.3 ml of borate buffer were added. After 10 min, 0.3 ml of this solution were added again each to 0.3 ml of serial dilutions of anitserum. The suspensions were mixed and left for 20 h at 37 degrees C and after this time for 1 h at room temperature. Then the reactions were read. M. suipneumoniae and M. hyopneumoniae were found to be identical or very close related strains. Between M. hyorhinis and M. sp. E9 relationship was noted too. M. granularum was different to all other investigated strains of mycoplasma. All results of Latex agglutination are in agreement with investigations performed with the aid of other serological methods and of electrophoretic separations of cell proteins of these mycoplasma.", "contents": "[Differentiation of swine-Mycoplasma by latex-agglutination (author's transl)]. The strains of Mycoplasma were grown in Shittlestone medium for 3-5 days. After centrifugation and washing, the mycoplasm were freeze-dried and stored at -20 degrees C. From this stock material immune sera and antigens were prepared. The immune sera were prepared by immunization of rabbits with a suspension of mycoplasma (2,2 mg dry weight per ml) and complete Freund's adjuvant. For the first immunication, 6.6 mg of antigen were injected into rabbits at different sites. 3 weeks later the second immunization followed by the intramuscular route (4.4 mg of antigen). The third and fourth immunizations were identical to the second one. Antiserum was obtained as usual. In order to avoid unspecific reactions in the latex agglutination, 1 ml of antiserum was added for absorption to 200 mg of freeze-dried sterile Whittlestone medium over 2 days at 4 degrees C. Antigen was prepared by ultrasonic disruption of mycoplasma (20 mg dry weight/ml physiological saline) and centrifugation 17300 X g, 30 min). The supernatant was used as antigen. The latex agglutination was performed in 0.1 M borate buffer pH 8,2. For preparation of the latex antigen compound 0.2 ml of a latex suspension (diluted 5 fold with water) were moxed with 0.5 ml of an antigen suspension (diluted 16 fold with buffer). After 10 min at room temperature, 4.3 ml of borate buffer were added. After 10 min, 0.3 ml of this solution were added again each to 0.3 ml of serial dilutions of anitserum. The suspensions were mixed and left for 20 h at 37 degrees C and after this time for 1 h at room temperature. Then the reactions were read. M. suipneumoniae and M. hyopneumoniae were found to be identical or very close related strains. Between M. hyorhinis and M. sp. E9 relationship was noted too. M. granularum was different to all other investigated strains of mycoplasma. All results of Latex agglutination are in agreement with investigations performed with the aid of other serological methods and of electrophoretic separations of cell proteins of these mycoplasma."} {"id": "PMID:1274501", "title": "[Concerning the question of the bactericidal action of organic N-bromoamines: experiments with N,N-dibromo-tert.-butylamine (author's transl)].", "content": "For the first time a defined N-fromoamine was examined on its bactericidal behaviour. In accordance with the \"Richtlinien f\u00fcr die Pr\u00fcfung chemischer Desinfektionsmittel\" (3. Aufl. Stuttgart: Gustav Fischer Verlag 1972), the action of the substance (1,5 X 10(-3) - 1,5 X 10(-5) M aqueous solution) on the germs E. coli, Proteus vulgaris, Ps. aeruginosa und Staph. aureus SG 511 was tested. As can be seen in Tab. 1, N,N-Dibromo-tert.-butylamine (1,5 X 10(-3) and 1,5 X 10(-4) M/I is showing a bactericidal action on all tested germs.", "contents": "[Concerning the question of the bactericidal action of organic N-bromoamines: experiments with N,N-dibromo-tert.-butylamine (author's transl)]. For the first time a defined N-fromoamine was examined on its bactericidal behaviour. In accordance with the \"Richtlinien f\u00fcr die Pr\u00fcfung chemischer Desinfektionsmittel\" (3. Aufl. Stuttgart: Gustav Fischer Verlag 1972), the action of the substance (1,5 X 10(-3) - 1,5 X 10(-5) M aqueous solution) on the germs E. coli, Proteus vulgaris, Ps. aeruginosa und Staph. aureus SG 511 was tested. As can be seen in Tab. 1, N,N-Dibromo-tert.-butylamine (1,5 X 10(-3) and 1,5 X 10(-4) M/I is showing a bactericidal action on all tested germs."} {"id": "PMID:1274502", "title": "[The carcinoembryonic antigen in the population of an industrial area (author's transl)].", "content": "The CEA level from human serum of male individuals born in 1924 living in different regions was determined. 527 test persons from the industrial city Duisburg, 132 from the town Siegburg and 389 from a country region in Kreis Gummersbach were investigated. Questionnaires were distributed for informations about maladies, smoking usage and workshop place. The CEA levels were distinctly increased in statistical examination of the industrial district. Smoking raised the CEA levels considerably. More cases of bronchial diseases with elevated CEA values were registrated in the population of the industrial city. The influence of workshop conditions was investigated on persons working in factories and offices. For the country region the CEA levels of these two groups resulted in negligible differences. However, the CEA levels of factory workers in the industrial city were found to be significantly increased in comparison with office workers for both, smokers and nonsmokers.", "contents": "[The carcinoembryonic antigen in the population of an industrial area (author's transl)]. The CEA level from human serum of male individuals born in 1924 living in different regions was determined. 527 test persons from the industrial city Duisburg, 132 from the town Siegburg and 389 from a country region in Kreis Gummersbach were investigated. Questionnaires were distributed for informations about maladies, smoking usage and workshop place. The CEA levels were distinctly increased in statistical examination of the industrial district. Smoking raised the CEA levels considerably. More cases of bronchial diseases with elevated CEA values were registrated in the population of the industrial city. The influence of workshop conditions was investigated on persons working in factories and offices. For the country region the CEA levels of these two groups resulted in negligible differences. However, the CEA levels of factory workers in the industrial city were found to be significantly increased in comparison with office workers for both, smokers and nonsmokers."} {"id": "PMID:1274503", "title": "[External quality control measures for blood lead analysis of persons living in a high lead exposure area (author's transl)].", "content": "Analytical laboratories engaged in studies regarding the exposure of larger population groups to lead should--for the sake of better intercomparability of data--subject themselves to internal and external quality control. In this paper an example of external quality control for blood lead, ALA-D and FEP analysis by 3 institutes is given. Evaluation by correlation analysis showed satisfactory results for all 3 parameters studied. Apart from discussing the results, suggestions are made regarding conduction of realistic quality control measures for the 3 lead-dependent biological exposure parameters.", "contents": "[External quality control measures for blood lead analysis of persons living in a high lead exposure area (author's transl)]. Analytical laboratories engaged in studies regarding the exposure of larger population groups to lead should--for the sake of better intercomparability of data--subject themselves to internal and external quality control. In this paper an example of external quality control for blood lead, ALA-D and FEP analysis by 3 institutes is given. Evaluation by correlation analysis showed satisfactory results for all 3 parameters studied. Apart from discussing the results, suggestions are made regarding conduction of realistic quality control measures for the 3 lead-dependent biological exposure parameters."} {"id": "PMID:1274504", "title": "[Exposed lead dioxide candles analyzed by a volumetric method, carried out as laboratory and field tests in Innsbruck (author's transl)].", "content": "Working up a great number of \"lead-Dioxide-Candles\" it took much less time to determine sulphate by a method of volumetric analysis with Ba(ClO4)2 and thoron or methylsulfonazo III as indicators compared with the so far used gravimetric determination of sulphate. With some training everybody will be able to make out the exact endpoint of the titration using thoron as indicator. The limits of error and the results gained from field-trials are shown. The possibilities of making statements of hygienically regional planning are discussed.", "contents": "[Exposed lead dioxide candles analyzed by a volumetric method, carried out as laboratory and field tests in Innsbruck (author's transl)]. Working up a great number of \"lead-Dioxide-Candles\" it took much less time to determine sulphate by a method of volumetric analysis with Ba(ClO4)2 and thoron or methylsulfonazo III as indicators compared with the so far used gravimetric determination of sulphate. With some training everybody will be able to make out the exact endpoint of the titration using thoron as indicator. The limits of error and the results gained from field-trials are shown. The possibilities of making statements of hygienically regional planning are discussed."} {"id": "PMID:1274505", "title": "[Basic concept for the judgement of the results of dustfall measuring in the Alps (author's transl)].", "content": "At the time extensive measurements are made in the Austrian part of the Alps to find out the elevation of the fundamental load of dustfall according to the methode of BERGERHOFF. Thereby the authors had to solve the fundamental question to find a system for estimation. In Austria the results of measurements of dustfall were classified usually according to the \"Technische Anleitung zur Reinhaltung der Luft 1964.\" It appeared that the introduction did not achieve the problem because of the special geografical, meteorological and economical data of the researched part of the Alps which at that time has about 30 000 km2. Similar applies to the new standards of the TAL 1974 and that recommendations of the \"Deutscher B\u00e4derverband\" to estimate health resorts, recreation areas and mineral springs. Therefore a special model for estimating was developed which differentiate among the average of a year and the maximum of the average of a month, the general housing-areas, recreation areas and standards for industrial areas. The suggested limits are under the limits which are used today in Germany. The results of measurements of dustfall are discussed.", "contents": "[Basic concept for the judgement of the results of dustfall measuring in the Alps (author's transl)]. At the time extensive measurements are made in the Austrian part of the Alps to find out the elevation of the fundamental load of dustfall according to the methode of BERGERHOFF. Thereby the authors had to solve the fundamental question to find a system for estimation. In Austria the results of measurements of dustfall were classified usually according to the \"Technische Anleitung zur Reinhaltung der Luft 1964.\" It appeared that the introduction did not achieve the problem because of the special geografical, meteorological and economical data of the researched part of the Alps which at that time has about 30 000 km2. Similar applies to the new standards of the TAL 1974 and that recommendations of the \"Deutscher B\u00e4derverband\" to estimate health resorts, recreation areas and mineral springs. Therefore a special model for estimating was developed which differentiate among the average of a year and the maximum of the average of a month, the general housing-areas, recreation areas and standards for industrial areas. The suggested limits are under the limits which are used today in Germany. The results of measurements of dustfall are discussed."} {"id": "PMID:1274506", "title": "[A vibrating bed aerosol generator for fibrous and powder dust particles (author's transl)].", "content": "A fluidized bed with defined mechanical vibrations has been used for the pulverization of powders of fibrous and spherical particles. By means of this process, it was possible to prepare for practical purposes useful aerosols with constant concentrations. In certain size ranges the concentrations as well as the fiber and particle size distribution were adjustable and could be varied as a function of physical properties of the vibrating fluidized bed.", "contents": "[A vibrating bed aerosol generator for fibrous and powder dust particles (author's transl)]. A fluidized bed with defined mechanical vibrations has been used for the pulverization of powders of fibrous and spherical particles. By means of this process, it was possible to prepare for practical purposes useful aerosols with constant concentrations. In certain size ranges the concentrations as well as the fiber and particle size distribution were adjustable and could be varied as a function of physical properties of the vibrating fluidized bed."} {"id": "PMID:1274507", "title": "[Blood pressure and pulse frequency during oral intake of cadmium sulfide in animal experiment].", "content": "Female wistar rats were given cadmium sulfide in various concentrations in their chow (26 mg CdS/kg feed and 52 mg CdS/kg feed). After a three month trial no significant changes in blood pressure could be seen. The pulse frequencies showed the falling tendency with increasing weight, as already seen in healthy rats.", "contents": "[Blood pressure and pulse frequency during oral intake of cadmium sulfide in animal experiment]. Female wistar rats were given cadmium sulfide in various concentrations in their chow (26 mg CdS/kg feed and 52 mg CdS/kg feed). After a three month trial no significant changes in blood pressure could be seen. The pulse frequencies showed the falling tendency with increasing weight, as already seen in healthy rats."} {"id": "PMID:1274508", "title": "[Positive und negative ions influence on the activity of the adrenal cortex (author's transl)].", "content": "The cortisol level in the serum of mice, which had been exposed to the influence of negatively or positively ionized air for 30 minutes, was determined by means of competitive protein fixation. Under the influence of both ion moieties, the cortisol level rose to twice the physiological norm (p less than 0,001 in both cases). - Theoretically the inhaled air ions might exert influence on the regulatory cycle hypothalamus - hypophysis - ACTH - adrenal cortex both neurogenically and directly via the circulatory system, thereby changing the cortisol level. For this reason, the determination of ACTH, as well as of cortisol after hypophysis exstirpation, must be regarded as a prerequisite for further investigations.", "contents": "[Positive und negative ions influence on the activity of the adrenal cortex (author's transl)]. The cortisol level in the serum of mice, which had been exposed to the influence of negatively or positively ionized air for 30 minutes, was determined by means of competitive protein fixation. Under the influence of both ion moieties, the cortisol level rose to twice the physiological norm (p less than 0,001 in both cases). - Theoretically the inhaled air ions might exert influence on the regulatory cycle hypothalamus - hypophysis - ACTH - adrenal cortex both neurogenically and directly via the circulatory system, thereby changing the cortisol level. For this reason, the determination of ACTH, as well as of cortisol after hypophysis exstirpation, must be regarded as a prerequisite for further investigations."} {"id": "PMID:1274514", "title": "Familial occurrence of giant cell hepatitis in infancy.", "content": "The repeated occurrence within one family or giant cell hepatitis terminating in death is reported. The familial form of giant cell hepatitis has a poorer prognosis than that occuring sporadically. In the first case, reported earlier, primary liver cancer developed within a short time. In the second case, reported here, the progression of the course of the disease which terminated in cirrhosis was followed in a series of histological examinatons made at five different points of time. Electronmicroscopic examination were also conducted.", "contents": "Familial occurrence of giant cell hepatitis in infancy. The repeated occurrence within one family or giant cell hepatitis terminating in death is reported. The familial form of giant cell hepatitis has a poorer prognosis than that occuring sporadically. In the first case, reported earlier, primary liver cancer developed within a short time. In the second case, reported here, the progression of the course of the disease which terminated in cirrhosis was followed in a series of histological examinatons made at five different points of time. Electronmicroscopic examination were also conducted."} {"id": "PMID:1274515", "title": "Hepatic vascular anomalies in nonparasitic cysts of the liver.", "content": "Vascular abnormalities demonstrated by angiography in 3 patients with nonparasitic liver cyst are described. In two cases of polycystic liver, dilated and mutually anastomosing hepatic vein branches were seen around a cyst as opacified by hepatic venography, and in one case of solitary liver cyst, anastomoses between large portal branches and a right hepatic vein was demonstrated by celiac angiography. These vascular abnormalities most likely represent developmental malformation along with aberrant bile duct formation expressed in the form of cystic liver. To exclude the possibility of these changes being secondary to expansion of the cyst, an angiographic study of excised polycystic liver was carried out, and it was found that cyst enlargement produced displacement and thinning but no anastomosis of the intrahepatic blood vessels.", "contents": "Hepatic vascular anomalies in nonparasitic cysts of the liver. Vascular abnormalities demonstrated by angiography in 3 patients with nonparasitic liver cyst are described. In two cases of polycystic liver, dilated and mutually anastomosing hepatic vein branches were seen around a cyst as opacified by hepatic venography, and in one case of solitary liver cyst, anastomoses between large portal branches and a right hepatic vein was demonstrated by celiac angiography. These vascular abnormalities most likely represent developmental malformation along with aberrant bile duct formation expressed in the form of cystic liver. To exclude the possibility of these changes being secondary to expansion of the cyst, an angiographic study of excised polycystic liver was carried out, and it was found that cyst enlargement produced displacement and thinning but no anastomosis of the intrahepatic blood vessels."} {"id": "PMID:1274516", "title": "Liver changes in burns, as seen in the clinical morphologic picture.", "content": "It was shown in a group of 59 patients with large thermic injuries that neither surgical treatment and the type of anesthesia and/or possibly some other therapy such as modern antibiotics, nor the age factor influence significantly liver changes which can almost always be found in burns disease. Undoubtedly, primarily the period of sepsis or toxemia has an unfavourable hepatotrophic effect - the decisive role being played by the bacterial infection of wound surfaces. A clinical laboratory and morphological picture of liver changes is given.", "contents": "Liver changes in burns, as seen in the clinical morphologic picture. It was shown in a group of 59 patients with large thermic injuries that neither surgical treatment and the type of anesthesia and/or possibly some other therapy such as modern antibiotics, nor the age factor influence significantly liver changes which can almost always be found in burns disease. Undoubtedly, primarily the period of sepsis or toxemia has an unfavourable hepatotrophic effect - the decisive role being played by the bacterial infection of wound surfaces. A clinical laboratory and morphological picture of liver changes is given."} {"id": "PMID:1274517", "title": "Gastro-oesophageal reflux disease: correlation of subjective symptoms with 7 objective oesophageal function tests.", "content": "Seven tests which have been recommended for the diagnosis of gastro-esophageal reflux were applied in 24 healthy controls and in 48 patients with symptoms of reflux disease. The correlation coefficient of test results with the subjective symptoms of the patient decreased in the following order: 1) acid clearance from the distal esophagus (r = 0.558, p less than 0.001), 2) suction biopsy 5 cm above lower esophageal sphincter (LES) with evaluation of granulocytic infiltrates (r = 0.450, p less 0.001), 3) radiological demonstration of hiatal hernia (r = 0.435, p less than 0.001), 4) reflux provocation test (r = 359, p less than 0.01), 5) modified Bernstein test (r = 0.322, p less than 0.01), 6) acid relux test (r = 0.252, p less than 0.05), 7) resting pressure of LES (r = 0.246, p less than 0.05). Results of the Maudsley Personality Inventory were not correlated with subjective symptoms (r = 0.188, p greater than 0.1). By stepwise multiple regression analysis it was shown that optimal diagnosis of reflux is achieved by combination the following 4 procedures: 1) acid clearance, 2) modified Bernstein test, 3) suction biopsy, and 4) radiology.", "contents": "Gastro-oesophageal reflux disease: correlation of subjective symptoms with 7 objective oesophageal function tests. Seven tests which have been recommended for the diagnosis of gastro-esophageal reflux were applied in 24 healthy controls and in 48 patients with symptoms of reflux disease. The correlation coefficient of test results with the subjective symptoms of the patient decreased in the following order: 1) acid clearance from the distal esophagus (r = 0.558, p less than 0.001), 2) suction biopsy 5 cm above lower esophageal sphincter (LES) with evaluation of granulocytic infiltrates (r = 0.450, p less 0.001), 3) radiological demonstration of hiatal hernia (r = 0.435, p less than 0.001), 4) reflux provocation test (r = 359, p less than 0.01), 5) modified Bernstein test (r = 0.322, p less than 0.01), 6) acid relux test (r = 0.252, p less than 0.05), 7) resting pressure of LES (r = 0.246, p less than 0.05). Results of the Maudsley Personality Inventory were not correlated with subjective symptoms (r = 0.188, p greater than 0.1). By stepwise multiple regression analysis it was shown that optimal diagnosis of reflux is achieved by combination the following 4 procedures: 1) acid clearance, 2) modified Bernstein test, 3) suction biopsy, and 4) radiology."} {"id": "PMID:1274518", "title": "Portal and peripheral plasma folates after ingestion of folic acid.", "content": "Folic acid in amounts of 2 mumol (0.88 mg) was given by mouth to four patients who had undergone portal vein catheterization. All had normal liver function. The increase in folates in plasma obtained from portal and peripheral veins was followed for three hours with the use of L. casei and S. faecalis as test organisms. The results lend support to the assumption that the liver is the main site of methylation of folic acid when given in physiological amounts.", "contents": "Portal and peripheral plasma folates after ingestion of folic acid. Folic acid in amounts of 2 mumol (0.88 mg) was given by mouth to four patients who had undergone portal vein catheterization. All had normal liver function. The increase in folates in plasma obtained from portal and peripheral veins was followed for three hours with the use of L. casei and S. faecalis as test organisms. The results lend support to the assumption that the liver is the main site of methylation of folic acid when given in physiological amounts."} {"id": "PMID:1274519", "title": "Tests of pancreatic function using 75Se-selenomethionine.", "content": "Pancreatic function was investigated in 43 patients using a combination of conventional and subtraction scans of the pancreas and duodenal aspiration of the 75Se-Selenomethionine injected, in the time periods 60-150 minutes, 90-120 minutes and 105-150 minutes after injection. Patients with chronic alcoholism, chronic pancreatitis, pancreatic carcinoma, extrahepatic biliary obstruction and liver disease were included. Seven patients with no evidence of gastro-intestinal disease served as controls. Pancreatic scanning provided eight false positive and two false negative results (23.3%) and with 75Se-Selenomethionine excretion at 105-150 minutes, six false results were obtained (14%). In only one patient was a false positive result obtained with both scans and the 75Se-Selenomethionine test. The performance of conventional and subtraction scans of the pancreas with measurement of 75Se-Selenomethionine activity in the duodenal aspirate collected from 105-150 minutes after injection provides a convenient means of testing pancreatic exocrine function in a single three hour session.", "contents": "Tests of pancreatic function using 75Se-selenomethionine. Pancreatic function was investigated in 43 patients using a combination of conventional and subtraction scans of the pancreas and duodenal aspiration of the 75Se-Selenomethionine injected, in the time periods 60-150 minutes, 90-120 minutes and 105-150 minutes after injection. Patients with chronic alcoholism, chronic pancreatitis, pancreatic carcinoma, extrahepatic biliary obstruction and liver disease were included. Seven patients with no evidence of gastro-intestinal disease served as controls. Pancreatic scanning provided eight false positive and two false negative results (23.3%) and with 75Se-Selenomethionine excretion at 105-150 minutes, six false results were obtained (14%). In only one patient was a false positive result obtained with both scans and the 75Se-Selenomethionine test. The performance of conventional and subtraction scans of the pancreas with measurement of 75Se-Selenomethionine activity in the duodenal aspirate collected from 105-150 minutes after injection provides a convenient means of testing pancreatic exocrine function in a single three hour session."} {"id": "PMID:1274521", "title": "The \"urea index\" as a marker of portal flow direction in cirrhosis of the liver.", "content": "In a control group (n = 50) and in 52 patients with cirrhosis, urea was administered orally and ratios for hepatic venous/arterial increment were determined up to 120 minutes after loading. A complete, hepatofugal diversion of the portal blood flow would result in ratios less than or equal to 1. The best discrimination between controls and cirrhotics was obtained with the 0-15 minute ratio (\"urea index\") which has a normal lower limit of 1.25. In cirrhosis an urea index less than or equal to 1.2 is correlated with an abnormal ammonia test and with the presence of marked portal hypertension (hepatic sinusoidal pressure greater than or equal to 8 mmHg, N: 0-3 mmHg). Ascites occurs more often in patients with cirrhosis and a low index. Regardless of the urea index value, ascites in cirrhosis is associated with an hepatic sinusoidal pressure greater than or equal to 8 mmHg. The urea index procedure may easily be conducted together with the measurement of hepatic sinusoidal pressure.", "contents": "The \"urea index\" as a marker of portal flow direction in cirrhosis of the liver. In a control group (n = 50) and in 52 patients with cirrhosis, urea was administered orally and ratios for hepatic venous/arterial increment were determined up to 120 minutes after loading. A complete, hepatofugal diversion of the portal blood flow would result in ratios less than or equal to 1. The best discrimination between controls and cirrhotics was obtained with the 0-15 minute ratio (\"urea index\") which has a normal lower limit of 1.25. In cirrhosis an urea index less than or equal to 1.2 is correlated with an abnormal ammonia test and with the presence of marked portal hypertension (hepatic sinusoidal pressure greater than or equal to 8 mmHg, N: 0-3 mmHg). Ascites occurs more often in patients with cirrhosis and a low index. Regardless of the urea index value, ascites in cirrhosis is associated with an hepatic sinusoidal pressure greater than or equal to 8 mmHg. The urea index procedure may easily be conducted together with the measurement of hepatic sinusoidal pressure."} {"id": "PMID:1274522", "title": "Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. I. Light microscopy observations.", "content": "Explants from seven nerve sheath tumors (four cranial and three spinal) induced in rats by transplacental ethylnitrosourea were grown on collagen-coated coverslips and in organ culture systems, using sponge foam matrices and Millipore filter platforms. Their sequential morphological features in vitro were compared to those of a human acoustic Schwannoma maintained in similar culture systems. The original experimental tumors were either undifferentiated or poorly malignant Schwannomas. In cultures on collagen-coated coverslips the explants demonstrated cellular features that were considerably more anaplastic than those of the human acoustic Schwannoma. On the other hand, in organ culture systems, in which viable cultures were maintained up to 82 days, many of the experimental tumor explants exhibited progressive differentiaiton, with nuclear palisading, increasing whorl formation and abundant reticulin fibers, and their pattern of histological organization came therefore closely to resemble that of the cultured acoustic Schwannoma. Unlike the latter, however, the cultured experimental tumors infiltrated the sponge foam matrices, a feature that mimicked the invasive character of the original tumors in vivo. Included normal ganglion cells remained demonstrable in the cultures up to 69 in vitro.", "contents": "Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. I. Light microscopy observations. Explants from seven nerve sheath tumors (four cranial and three spinal) induced in rats by transplacental ethylnitrosourea were grown on collagen-coated coverslips and in organ culture systems, using sponge foam matrices and Millipore filter platforms. Their sequential morphological features in vitro were compared to those of a human acoustic Schwannoma maintained in similar culture systems. The original experimental tumors were either undifferentiated or poorly malignant Schwannomas. In cultures on collagen-coated coverslips the explants demonstrated cellular features that were considerably more anaplastic than those of the human acoustic Schwannoma. On the other hand, in organ culture systems, in which viable cultures were maintained up to 82 days, many of the experimental tumor explants exhibited progressive differentiaiton, with nuclear palisading, increasing whorl formation and abundant reticulin fibers, and their pattern of histological organization came therefore closely to resemble that of the cultured acoustic Schwannoma. Unlike the latter, however, the cultured experimental tumors infiltrated the sponge foam matrices, a feature that mimicked the invasive character of the original tumors in vivo. Included normal ganglion cells remained demonstrable in the cultures up to 69 in vitro."} {"id": "PMID:1274523", "title": "Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. II. Electron microscopy observations.", "content": "The sequential electron microscopic features of six malignant nerve sheath tumors (three cranial and three spinal) induced in rats by transplacental ethylnitrosourea and maintained in organ culture systems were compared with those of a human acoustic Schwannoma similarly cultured. After 4 weeks in vitro, the malignant tumor cells often showed progressive elongation of their processes, with the development of an interdigitating pattern resembling that seen in well-differentiated Schwannomas. This was accompanied by an increase of microtubules. Basal lamina formation, less well-developed and less complete than in the benign Schwannoma in this study, was maintained in culture. Some explants demonstrated an increase in number and width of collagen fibrils, accompanied by a relative concomitant decrease of inter-cellular basement membrane material. The malignant tumor cells also showed numerous micropinocytotic vesicles and various junctional complexes, which are characteristic of perineurial cells. Since the origin of the experimental tumors from adult Schwann cells seems well established, this apparent contradiction is best resolved by the concept that Schwann cells and perineurial fibroblasts are functional variants of the same cell type.", "contents": "Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. II. Electron microscopy observations. The sequential electron microscopic features of six malignant nerve sheath tumors (three cranial and three spinal) induced in rats by transplacental ethylnitrosourea and maintained in organ culture systems were compared with those of a human acoustic Schwannoma similarly cultured. After 4 weeks in vitro, the malignant tumor cells often showed progressive elongation of their processes, with the development of an interdigitating pattern resembling that seen in well-differentiated Schwannomas. This was accompanied by an increase of microtubules. Basal lamina formation, less well-developed and less complete than in the benign Schwannoma in this study, was maintained in culture. Some explants demonstrated an increase in number and width of collagen fibrils, accompanied by a relative concomitant decrease of inter-cellular basement membrane material. The malignant tumor cells also showed numerous micropinocytotic vesicles and various junctional complexes, which are characteristic of perineurial cells. Since the origin of the experimental tumors from adult Schwann cells seems well established, this apparent contradiction is best resolved by the concept that Schwann cells and perineurial fibroblasts are functional variants of the same cell type."} {"id": "PMID:1274524", "title": "Morphological differences between the atrophied small muscle fibres in amyotrophic lateral sclerosis and Werdnig-Hoffmann disease.", "content": "Muscle biopsies from 5 cases of Werdnig-Hoffmann disease and 4 cases of ALS were investigated by histology and electronmicroscopy. The differences in morphology found in the atrophic muscle fibers in ALS and in W.H. disease consisted mainly in the shape and structure of their cells and the number of the nuclei. Atrophic muscle fibres irregular in shape and size with degenerative changes and accumulated nuclei observed in ALS were markedly different from the picture of the fibres in W.H. disease. The presence of small muscle cells uniform diameter with well preserved architecture and numerous myotube-like cells seem to indicate a foetal defect in children with W.H. disease.", "contents": "Morphological differences between the atrophied small muscle fibres in amyotrophic lateral sclerosis and Werdnig-Hoffmann disease. Muscle biopsies from 5 cases of Werdnig-Hoffmann disease and 4 cases of ALS were investigated by histology and electronmicroscopy. The differences in morphology found in the atrophic muscle fibers in ALS and in W.H. disease consisted mainly in the shape and structure of their cells and the number of the nuclei. Atrophic muscle fibres irregular in shape and size with degenerative changes and accumulated nuclei observed in ALS were markedly different from the picture of the fibres in W.H. disease. The presence of small muscle cells uniform diameter with well preserved architecture and numerous myotube-like cells seem to indicate a foetal defect in children with W.H. disease."} {"id": "PMID:1274525", "title": "The target phenomenon in human muscle: a comparative light microscopic histochemical and electron microscopic study.", "content": "A large number of target fibres is observed in a muscle biopsy from a patient with an acute flaccid paraplegia of the lower limbs due to a polyneuroradiculopathy of unknown origin. With the electron microscope up to 4 structural zones are seen in the target fibers. The histochemical and ultrastructural observations in this case, suggest that the \"target fiber\" phenomenon is due to a disturbed trophic influence of the nervous system.", "contents": "The target phenomenon in human muscle: a comparative light microscopic histochemical and electron microscopic study. A large number of target fibres is observed in a muscle biopsy from a patient with an acute flaccid paraplegia of the lower limbs due to a polyneuroradiculopathy of unknown origin. With the electron microscope up to 4 structural zones are seen in the target fibers. The histochemical and ultrastructural observations in this case, suggest that the \"target fiber\" phenomenon is due to a disturbed trophic influence of the nervous system."} {"id": "PMID:1274526", "title": "[Cerebral cortex in normal pressure hydrocephalus: an electron microscopy study (author's transl)].", "content": "A cortical biopsy was taken at the time when ventricular pressure was measured, or a ventriculo-atrial shunt placed, in 11 patients with Normal Pressure Hydrocephalus (N.P.H.), and was studied with the electron microscope. In 9 cases, a rather typical electron microscopic picture with marked increase of extracellular space in an otherwise normal cortical neuropil was observed. 2 patients did not exhibit this pattern and, coincendentally, did not benefit from the placing of the shunt. As a control, about 600 cortical biopsies that had been taken for other reasons were reviewed. In the group, there were only 3 cortices that had a pattern of increased extracellular space similar to the described in N.P.H. On review of the clinico-pathologic data of these cases, it was felt that all 3 probably represented cases of normal pressure hydrocephalus. It is concluded that the ultrastructure of the cerebral cortex is of at least nosological interest in the study of N.P.H.", "contents": "[Cerebral cortex in normal pressure hydrocephalus: an electron microscopy study (author's transl)]. A cortical biopsy was taken at the time when ventricular pressure was measured, or a ventriculo-atrial shunt placed, in 11 patients with Normal Pressure Hydrocephalus (N.P.H.), and was studied with the electron microscope. In 9 cases, a rather typical electron microscopic picture with marked increase of extracellular space in an otherwise normal cortical neuropil was observed. 2 patients did not exhibit this pattern and, coincendentally, did not benefit from the placing of the shunt. As a control, about 600 cortical biopsies that had been taken for other reasons were reviewed. In the group, there were only 3 cortices that had a pattern of increased extracellular space similar to the described in N.P.H. On review of the clinico-pathologic data of these cases, it was felt that all 3 probably represented cases of normal pressure hydrocephalus. It is concluded that the ultrastructure of the cerebral cortex is of at least nosological interest in the study of N.P.H."} {"id": "PMID:1274527", "title": "[Hereditary neuropathic Portuguese type of amyloidosis (author's transl)].", "content": "Report of a 35 year old male with hereditary neuropathic amyloidosis of the portuguese type, the second known case in Germany. There are extensive nodular Congo red positive amyloid deposits in the endoneurium of the peripheral nerves which lead to displacement, compression atrophy and interruption of the endoneural fascicles. The amyloid fibril structure is specially noted by interference contrast microscopy. It can also be documented in unstained microscopic sections. Further extensive nodular deposits are present in the mesangium of the glomerula. The remaining organs show preponderantly affected vessel walls and collagen fibres.", "contents": "[Hereditary neuropathic Portuguese type of amyloidosis (author's transl)]. Report of a 35 year old male with hereditary neuropathic amyloidosis of the portuguese type, the second known case in Germany. There are extensive nodular Congo red positive amyloid deposits in the endoneurium of the peripheral nerves which lead to displacement, compression atrophy and interruption of the endoneural fascicles. The amyloid fibril structure is specially noted by interference contrast microscopy. It can also be documented in unstained microscopic sections. Further extensive nodular deposits are present in the mesangium of the glomerula. The remaining organs show preponderantly affected vessel walls and collagen fibres."} {"id": "PMID:1274528", "title": "Vacuolation of oligodendroglia in neoplastic perifocal edema.", "content": "Vacuolation of oligodendroglia, a new type of cytopathological change, has been described. The change is observed frequently at the perifocally edematous cerebral white matter adjacent to the metastatic lesions of carcinoma from the lung in all three cases examined. It is also present occasionally in association with astrocytoma. This condition is characterized by swelling of oligodendroglias due to numerous cytoplasmic vacuolations which contain the material identical with that of the extracellular edema fluid. In such cells, the nucleus is displaced and deformed by vacuoles but the nuclear chromatin and envelopes are arranged normally. By occupation of numerous large vacuoles the cytoplasm is divided into small areas, but the individual organelles are only minimally altered. The oligodendroglial vacuolation seems to be a phagocytic response to the edema fluid which contains proteinous macromolecules derived from blood-borne protein and necrotic material of brain tissue and neoplastic cells. The vacuolation may result in some oligodendroglial dysfunction in maintenance of myelin and probably be related with diffuse loss of myelin sheath in the longstanding brain edema secondary to neoplastic invasion. The vacuolated cells can be identified with light and electron microscopes in Epon-embedded sections of surgically removed tissue but not in paraffin sections.", "contents": "Vacuolation of oligodendroglia in neoplastic perifocal edema. Vacuolation of oligodendroglia, a new type of cytopathological change, has been described. The change is observed frequently at the perifocally edematous cerebral white matter adjacent to the metastatic lesions of carcinoma from the lung in all three cases examined. It is also present occasionally in association with astrocytoma. This condition is characterized by swelling of oligodendroglias due to numerous cytoplasmic vacuolations which contain the material identical with that of the extracellular edema fluid. In such cells, the nucleus is displaced and deformed by vacuoles but the nuclear chromatin and envelopes are arranged normally. By occupation of numerous large vacuoles the cytoplasm is divided into small areas, but the individual organelles are only minimally altered. The oligodendroglial vacuolation seems to be a phagocytic response to the edema fluid which contains proteinous macromolecules derived from blood-borne protein and necrotic material of brain tissue and neoplastic cells. The vacuolation may result in some oligodendroglial dysfunction in maintenance of myelin and probably be related with diffuse loss of myelin sheath in the longstanding brain edema secondary to neoplastic invasion. The vacuolated cells can be identified with light and electron microscopes in Epon-embedded sections of surgically removed tissue but not in paraffin sections."} {"id": "PMID:1274529", "title": "In vitro characteristics of a sacrococcygeal chordoma maintained in tissue and organ culture systems.", "content": "Explants of a human sacral chordoma were successfully maintained on collagen-coated coverslips, gelfoam sponge matrices, and Millipore filter platforms for up to 30 days. Tumor cells cultured on collagen-coated coverslips became increasingly vacuolated whereas those maintained in organ culture were entirely free of vacuoles after 22 days in vitro. A single basic tumor cell, small and polygonal with a large central spherical nucleus and abundant endoplasmic reticulum and Golgi apparatus, was recognized. Vacuoles were formed as the result of the progressive expansion of smooth endoplasmic reticulum. Coalescence of these vacuoles produced the physaliferous cell of light microscopy.", "contents": "In vitro characteristics of a sacrococcygeal chordoma maintained in tissue and organ culture systems. Explants of a human sacral chordoma were successfully maintained on collagen-coated coverslips, gelfoam sponge matrices, and Millipore filter platforms for up to 30 days. Tumor cells cultured on collagen-coated coverslips became increasingly vacuolated whereas those maintained in organ culture were entirely free of vacuoles after 22 days in vitro. A single basic tumor cell, small and polygonal with a large central spherical nucleus and abundant endoplasmic reticulum and Golgi apparatus, was recognized. Vacuoles were formed as the result of the progressive expansion of smooth endoplasmic reticulum. Coalescence of these vacuoles produced the physaliferous cell of light microscopy."} {"id": "PMID:1274530", "title": "Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. III. Melanin pigment and melanogenesis in experimental neurogenic tumors: a reappraisal of the histogenesis of pigmented nerve sheath tumors.", "content": "Four melanin pigment-containing intracranial tumors were found in three Long-Evans rats in the course of experimental oncogenesis by transplacental ethylnitrosourea (ENU). One of them was a leptomeningeal melanoma. Aside from the presence of scattered melanin-pigmented cells, the other three had the typical histological features of ENU-induced malignant nerve sheath tumors. Two of the three tumors were studied by electron microscopy and in tissue and organ culture systems. One of them demonstrated progressive melanogenesis in vitro; the other failed to produce more melanin and showed increasing differentiation, with a Schwannoma-like pattern by light microscopy. Melanosomes and premelanosomes were identified in both tumors by electron microscopy; the other fine structural features were those of malignant Schwannomas. These observations are relevant to the controversy on the histogenesis of pigmented nerve sheath tumors occasionally encountered in man and on the relationship of these tumors to pigmented nevi. The findings in the present study support the view of Masson that neoplastic nerve sheath cells are capable of melanogenesis.", "contents": "Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. III. Melanin pigment and melanogenesis in experimental neurogenic tumors: a reappraisal of the histogenesis of pigmented nerve sheath tumors. Four melanin pigment-containing intracranial tumors were found in three Long-Evans rats in the course of experimental oncogenesis by transplacental ethylnitrosourea (ENU). One of them was a leptomeningeal melanoma. Aside from the presence of scattered melanin-pigmented cells, the other three had the typical histological features of ENU-induced malignant nerve sheath tumors. Two of the three tumors were studied by electron microscopy and in tissue and organ culture systems. One of them demonstrated progressive melanogenesis in vitro; the other failed to produce more melanin and showed increasing differentiation, with a Schwannoma-like pattern by light microscopy. Melanosomes and premelanosomes were identified in both tumors by electron microscopy; the other fine structural features were those of malignant Schwannomas. These observations are relevant to the controversy on the histogenesis of pigmented nerve sheath tumors occasionally encountered in man and on the relationship of these tumors to pigmented nevi. The findings in the present study support the view of Masson that neoplastic nerve sheath cells are capable of melanogenesis."} {"id": "PMID:1274531", "title": "[Fusiform enlargement of mechanic origin of a peripheral nerve (author's transl)].", "content": "This paper reports on the study of a symptomless fusiform enlargement of the superficial peroneal nerve. The swelling was located in the part of the nerve passing through the aponevrosis. On incision of the epineurium small swellings were seen in the nerve fascicles. A fascicular biopsy was done and the fascicles studied by teasing and by optic and electron microscopy. Isolated nerve fiber study gave evidence of segmental demyelinisation with subsequent remyelinisation in almost all the myelinated fibers. These abnormalities were only encountered in the swollen part of the fascicle. A striking proliferation of cells was demonstrated in isolated fibers by counterstaining with hematoxylin. Electron microscopy showed primary demyelinsation and cellular proliferation affecting Schwann-cells (without onion bulb formations), fibroblasts and giant-vacuolated histiocytes. There was also a massive increase of endoneurial fluid. A few B\u00fcnger bands were seen. These rare abnormalities appear to be caused by chronic irritation of the nerve in its passage through the aponebrosis.", "contents": "[Fusiform enlargement of mechanic origin of a peripheral nerve (author's transl)]. This paper reports on the study of a symptomless fusiform enlargement of the superficial peroneal nerve. The swelling was located in the part of the nerve passing through the aponevrosis. On incision of the epineurium small swellings were seen in the nerve fascicles. A fascicular biopsy was done and the fascicles studied by teasing and by optic and electron microscopy. Isolated nerve fiber study gave evidence of segmental demyelinisation with subsequent remyelinisation in almost all the myelinated fibers. These abnormalities were only encountered in the swollen part of the fascicle. A striking proliferation of cells was demonstrated in isolated fibers by counterstaining with hematoxylin. Electron microscopy showed primary demyelinsation and cellular proliferation affecting Schwann-cells (without onion bulb formations), fibroblasts and giant-vacuolated histiocytes. There was also a massive increase of endoneurial fluid. A few B\u00fcnger bands were seen. These rare abnormalities appear to be caused by chronic irritation of the nerve in its passage through the aponebrosis."} {"id": "PMID:1274532", "title": "Gap junctions between human meningioma cells maintained in organ culture.", "content": "Intercellular junctions were commonly observed in a human syncitial meningioma maintained in organ culture for up to 44 days in vitro (DIV) using gelatin sponge foam matrices. The junctions were identified as one of three types: desmosomes; tight junctions; or gap junctions. Of the three types, gap junctions were frequently encountered and showed preservation of their characteristic ladder-like substructure. The results suggest that organ culture provides an environment that may facilitate correlation of the structure and function of gap junctions between coupled human meningioma cells.", "contents": "Gap junctions between human meningioma cells maintained in organ culture. Intercellular junctions were commonly observed in a human syncitial meningioma maintained in organ culture for up to 44 days in vitro (DIV) using gelatin sponge foam matrices. The junctions were identified as one of three types: desmosomes; tight junctions; or gap junctions. Of the three types, gap junctions were frequently encountered and showed preservation of their characteristic ladder-like substructure. The results suggest that organ culture provides an environment that may facilitate correlation of the structure and function of gap junctions between coupled human meningioma cells."} {"id": "PMID:1274533", "title": "Cerebellar microgyria.", "content": "The histological features of cerebellar microgyria are described in a 15 month old infant. The bizarre appearance of this malformation seems to be the result of two basic factors: secondary fusion between preformed folia, and deficient and disorderly formation of the internal granule cell layer. The findings support the view according to which cerebellar microgyria is probably due to a pathological process involving the external granule cell layer during a relatively late period of cerebellar development.", "contents": "Cerebellar microgyria. The histological features of cerebellar microgyria are described in a 15 month old infant. The bizarre appearance of this malformation seems to be the result of two basic factors: secondary fusion between preformed folia, and deficient and disorderly formation of the internal granule cell layer. The findings support the view according to which cerebellar microgyria is probably due to a pathological process involving the external granule cell layer during a relatively late period of cerebellar development."} {"id": "PMID:1274534", "title": "Scanning transmission and conventional electron microscopic observation of previously identified protoplasmic astrocytes. A preliminary study.", "content": "Two different types of protoplasmic astrocytes were studied by scanning transmission and conventional electron microscopy in order to determine the exact nature of the aspect described by Chan Palay and Palay as velate astrocyte. This study provides new data about the usefulness of S.T.E.M and brings into question the results of the Palays.", "contents": "Scanning transmission and conventional electron microscopic observation of previously identified protoplasmic astrocytes. A preliminary study. Two different types of protoplasmic astrocytes were studied by scanning transmission and conventional electron microscopy in order to determine the exact nature of the aspect described by Chan Palay and Palay as velate astrocyte. This study provides new data about the usefulness of S.T.E.M and brings into question the results of the Palays."} {"id": "PMID:1274535", "title": "Fine needle aspiration biopsy of bone lesions: clinical value.", "content": "The clinical value of cytological aspiration biopsy in 85 patients with lytic bone lesions was studied. In 71 cases cytology was of diagnostic value, but in 14 cases it was inconclusive or misleading. The method is considered a simple primary diagnostic procedure especially in lytic bone lesions of uncertain nature.", "contents": "Fine needle aspiration biopsy of bone lesions: clinical value. The clinical value of cytological aspiration biopsy in 85 patients with lytic bone lesions was studied. In 71 cases cytology was of diagnostic value, but in 14 cases it was inconclusive or misleading. The method is considered a simple primary diagnostic procedure especially in lytic bone lesions of uncertain nature."} {"id": "PMID:1274537", "title": "Porous ceramics as a bone substitute in the medial condyle of the tibia. An experimental study in sheep.", "content": "A new porous ceramic material was tested for possible use as a bone substitute in regions exposed mainly to compressive forces. The porous ceramics were implanted into the medial condyle of the tibia of four sheep and left in position for 3 months. The operated tibia was then removed and sections were made of the implants. The sections were studied by transmitted light microscopy, microradiography and scanning electron microscopy. There was no apparent loss of function of the operated leg and the implants were found to be bound to the adjacent bone by ingrowth of bony tissue, in some regions to a depth of 2-3 mm. It is concluded that the properties of the porous ceramic implants justify a clinical trial, provided that the results of long-term animal experiments are equally satisfactory.", "contents": "Porous ceramics as a bone substitute in the medial condyle of the tibia. An experimental study in sheep. A new porous ceramic material was tested for possible use as a bone substitute in regions exposed mainly to compressive forces. The porous ceramics were implanted into the medial condyle of the tibia of four sheep and left in position for 3 months. The operated tibia was then removed and sections were made of the implants. The sections were studied by transmitted light microscopy, microradiography and scanning electron microscopy. There was no apparent loss of function of the operated leg and the implants were found to be bound to the adjacent bone by ingrowth of bony tissue, in some regions to a depth of 2-3 mm. It is concluded that the properties of the porous ceramic implants justify a clinical trial, provided that the results of long-term animal experiments are equally satisfactory."} {"id": "PMID:1274539", "title": "Primary tumours in the spine and pelvis in adolescents: clinical and radiological features.", "content": "In 34 patients in their two first decades of life with primary bone tumours in the spine and pelvis, the most common benign tumour was histiocytosis X and the most common malignant tumour, Ewing's sarcoma. X-rays were positive in 32 out of 34 cases but of little diagnostic value and primary complaints were without significance. The final diagnosis can only be made after a biopsy.", "contents": "Primary tumours in the spine and pelvis in adolescents: clinical and radiological features. In 34 patients in their two first decades of life with primary bone tumours in the spine and pelvis, the most common benign tumour was histiocytosis X and the most common malignant tumour, Ewing's sarcoma. X-rays were positive in 32 out of 34 cases but of little diagnostic value and primary complaints were without significance. The final diagnosis can only be made after a biopsy."} {"id": "PMID:1274541", "title": "Extraosseous variations of temperature during polymerization of acrylic cement in hip arthroplasties.", "content": "In order to evaluate the estraosseous temperature variations during polymerization of acrylic cement being used in hip arthroplasty, measurements were taken on the anterior aspect of the upper part of the femur and also in the ipsilateral iliac vein. No variations were observed in the blood stream. On the external surface of the upper femur, the greatest variations were of the order of 3 degrees C. The significance of these findings is discussed.", "contents": "Extraosseous variations of temperature during polymerization of acrylic cement in hip arthroplasties. In order to evaluate the estraosseous temperature variations during polymerization of acrylic cement being used in hip arthroplasty, measurements were taken on the anterior aspect of the upper part of the femur and also in the ipsilateral iliac vein. No variations were observed in the blood stream. On the external surface of the upper femur, the greatest variations were of the order of 3 degrees C. The significance of these findings is discussed."} {"id": "PMID:1274542", "title": "Necrosis of the femoral capital epiphysis occuring during human growth hormone therapy.", "content": "A girl with growth hormone deficiency developed a necrosis of the femoral capital epiphysis 6 months after the start of human growth hormone treatment. The compensatory growth spurt is believed to have caused an insufficient blood supply to the epiphysis, resulting in necrosis.", "contents": "Necrosis of the femoral capital epiphysis occuring during human growth hormone therapy. A girl with growth hormone deficiency developed a necrosis of the femoral capital epiphysis 6 months after the start of human growth hormone treatment. The compensatory growth spurt is believed to have caused an insufficient blood supply to the epiphysis, resulting in necrosis."} {"id": "PMID:1274544", "title": "Bilateral total hip arthroplasty: a simultaneous procedure.", "content": "Fifty patients undergoing bilateral total hip replacement as a simultaneous procedure at the Indiana University Medical Center were compared with 50 patients undergoing unilateral total hip replacement. There was an increase in phlebitis and myositis ossificans in the patients undergoing bilateral total hip replacement and while their range of motion was less, there was no difference in mortality with one death in each group. The hospital time for patients in the bilateral group averaged 1 week longer than for those with unilateral hip replacement. The operating time and blood loss in patients of the bilateral group was approximately twice that of patients in the control group. There have been no infections as yet in the bilateral group. On the basis of these preliminary results, we can consider bilateral total hip arthroplasty feasible although it carries a slightly increased risk.", "contents": "Bilateral total hip arthroplasty: a simultaneous procedure. Fifty patients undergoing bilateral total hip replacement as a simultaneous procedure at the Indiana University Medical Center were compared with 50 patients undergoing unilateral total hip replacement. There was an increase in phlebitis and myositis ossificans in the patients undergoing bilateral total hip replacement and while their range of motion was less, there was no difference in mortality with one death in each group. The hospital time for patients in the bilateral group averaged 1 week longer than for those with unilateral hip replacement. The operating time and blood loss in patients of the bilateral group was approximately twice that of patients in the control group. There have been no infections as yet in the bilateral group. On the basis of these preliminary results, we can consider bilateral total hip arthroplasty feasible although it carries a slightly increased risk."} {"id": "PMID:1274545", "title": "Treatment of fractures of the femoral neck by primary arthroplasty.", "content": "A total of 163 patients with fracture of the neck of the femur in the acute stage were treated at the Orthopaedic Clinics of H\u00e4rn\u00f6sand and Ostersund, between 1963 and 1970, by insertion of Moore's endoprosthesis. The patients were either above 70 years of age or were younger patients with debilitating diseases. The patients were followed up clinically for up to 9 years after operation, and 133 of them until death (average 3.4 years). The mortality within 6 weeks postoperatively was 9 per cent; other complications not producing late late sequelae were seen in 8 per cent and complications producing late sequelae in 5 per cent. A good functional result was achieved in 95 per cent of those surviving the immediate postoperative course. A careful review of a sample of the patients showed that 77 per cent were without pain and 93 per cent could manage activities of daily living.", "contents": "Treatment of fractures of the femoral neck by primary arthroplasty. A total of 163 patients with fracture of the neck of the femur in the acute stage were treated at the Orthopaedic Clinics of H\u00e4rn\u00f6sand and Ostersund, between 1963 and 1970, by insertion of Moore's endoprosthesis. The patients were either above 70 years of age or were younger patients with debilitating diseases. The patients were followed up clinically for up to 9 years after operation, and 133 of them until death (average 3.4 years). The mortality within 6 weeks postoperatively was 9 per cent; other complications not producing late late sequelae were seen in 8 per cent and complications producing late sequelae in 5 per cent. A good functional result was achieved in 95 per cent of those surviving the immediate postoperative course. A careful review of a sample of the patients showed that 77 per cent were without pain and 93 per cent could manage activities of daily living."} {"id": "PMID:1274546", "title": "Surgical exposure of the lesser trochanter and the medial proximal part of the femur.", "content": "An exposure of the medial proximal femur between the femoral artery and vein medially and the femoral nerve laterally is described. As far as the authors know, this exposure has not been described in the literature before. In their opinion it is to be preferred to the exposures already published when lesions of the medial proximal part of the femur are to be treated. Moreover, the exposure can be extended distally as described by Henry (1970).", "contents": "Surgical exposure of the lesser trochanter and the medial proximal part of the femur. An exposure of the medial proximal femur between the femoral artery and vein medially and the femoral nerve laterally is described. As far as the authors know, this exposure has not been described in the literature before. In their opinion it is to be preferred to the exposures already published when lesions of the medial proximal part of the femur are to be treated. Moreover, the exposure can be extended distally as described by Henry (1970)."} {"id": "PMID:1274547", "title": "Dysplasia epiphysealis hemimelica.", "content": "Four typical cases of dysplasia epiphysealis hemimelica are reported, the age when first examined varying from 18 months to 5 years. The observation periods varied from 3-20 years. After fusion between the accessory ossification centres of the osteochondroma and the regular epiphysis, no further enlargement was observed. In three cases an enlarged medial femoral condyle was resected, in two cases the resection was done through bone, leaving a non-cartilaginous surface in the knee joint. This procedure seems to have no harmful consequences; one of the patients seen 19 years later had no complaints, and the knee joint appeared almost normal on X-rays.", "contents": "Dysplasia epiphysealis hemimelica. Four typical cases of dysplasia epiphysealis hemimelica are reported, the age when first examined varying from 18 months to 5 years. The observation periods varied from 3-20 years. After fusion between the accessory ossification centres of the osteochondroma and the regular epiphysis, no further enlargement was observed. In three cases an enlarged medial femoral condyle was resected, in two cases the resection was done through bone, leaving a non-cartilaginous surface in the knee joint. This procedure seems to have no harmful consequences; one of the patients seen 19 years later had no complaints, and the knee joint appeared almost normal on X-rays."} {"id": "PMID:1274548", "title": "Growth of the rat femur in diffusion chambers.", "content": "Growth in the length of 9-day-old rat femurs, isolated and cultivated in diffusion chambers, was studied for a limited period of 16 days. An increment of 40 per cent of the in vivo length was observed. It could be established that the elongation was due to chondral growth, of which 40 per cent occurred at the proximal and 60 per cent at the distal end of the bone during the 16 days of observation. When the trochanteric or the head epiphyses with their physeal plates were resected, no statistically significant loss in total length occurred. A small but statistically highly significant biphasic growth due to enchondral ossification was found. Resection of the trochanter produced a widening of the cervico-diaphyseal angle (valgisation) of an average of 11.2 degrees. The findings in this series of isolated femurs are --in a general way--similar to those observed in the living animal.", "contents": "Growth of the rat femur in diffusion chambers. Growth in the length of 9-day-old rat femurs, isolated and cultivated in diffusion chambers, was studied for a limited period of 16 days. An increment of 40 per cent of the in vivo length was observed. It could be established that the elongation was due to chondral growth, of which 40 per cent occurred at the proximal and 60 per cent at the distal end of the bone during the 16 days of observation. When the trochanteric or the head epiphyses with their physeal plates were resected, no statistically significant loss in total length occurred. A small but statistically highly significant biphasic growth due to enchondral ossification was found. Resection of the trochanter produced a widening of the cervico-diaphyseal angle (valgisation) of an average of 11.2 degrees. The findings in this series of isolated femurs are --in a general way--similar to those observed in the living animal."} {"id": "PMID:1274549", "title": "The mechanical and structural characteristics of the tibio-fibular interosseous membrane.", "content": "The tibio-fibular interosseous membrane was studied in the scanning electron microscope. It is made up of two fibrous networks, a major one composed of large diameter fibres aggregated into bundles and a fine filamentous network, without a preferred orientation, between these main fibre bundles. Mechanical studies have shown that the interosseous membrane is stronger, but less extensible, parallel to the direction of the main fibre bundles which, therefore, probably have a load bearing function.", "contents": "The mechanical and structural characteristics of the tibio-fibular interosseous membrane. The tibio-fibular interosseous membrane was studied in the scanning electron microscope. It is made up of two fibrous networks, a major one composed of large diameter fibres aggregated into bundles and a fine filamentous network, without a preferred orientation, between these main fibre bundles. Mechanical studies have shown that the interosseous membrane is stronger, but less extensible, parallel to the direction of the main fibre bundles which, therefore, probably have a load bearing function."} {"id": "PMID:1274552", "title": "Suboccipital removal of acoustic neuromas. Results of 125 operations.", "content": "The surgical results obtained in 125 patients with acoustic neuromas, using the suboccipital approach, are reported. These results do not differ from those obtained in other neurosurgical materials, with the same distribution of tumour size, and the same surgical approach. The material consists of 20 medium size tumours, and 105 large. However, the results, regarding both mortality, postoperative facial paralysis as well as post-operative condition in general are unsatisfactory. A historical review of the development of the surgical treatment of acoustic neuromas is given, and the necessity of a closer neurosurgical-otologic cooperation is stressed, both with regard to diagnosis of the neuromas as well as the surgical treatment.", "contents": "Suboccipital removal of acoustic neuromas. Results of 125 operations. The surgical results obtained in 125 patients with acoustic neuromas, using the suboccipital approach, are reported. These results do not differ from those obtained in other neurosurgical materials, with the same distribution of tumour size, and the same surgical approach. The material consists of 20 medium size tumours, and 105 large. However, the results, regarding both mortality, postoperative facial paralysis as well as post-operative condition in general are unsatisfactory. A historical review of the development of the surgical treatment of acoustic neuromas is given, and the necessity of a closer neurosurgical-otologic cooperation is stressed, both with regard to diagnosis of the neuromas as well as the surgical treatment."} {"id": "PMID:1274550", "title": "Voluntary, non-visual control of the human vestibulo-ocular reflex.", "content": "Voluntary control of the human vestibulo-ocular reflex with and without visual targets was investigated. Subjects were rotated sinusoidally from 0.1 to 1.0 Hz using d.c. electro-oculography to record eye position. The ratio of eye to head movement, or gain, of the vestibulo-ocular reflex was measured. When subjects were rotated in the dark at 0.3 Hz whilst performing mental arithmetic the gain was 0.65. When subjects were asked to fixate imaginary targets in the dark that were stationary in space, the gain rose to 0.95. When they imagined targets rotating with them on the chair, the gain dropped to 0.35. Our results indicate that the ability to modulate the gain of the vestibulo-ocular reflex does not depend entirely on the smooth pursuit system. Higher centers must modulate eye velocity so that it is appropriate to the subject's choice of a frame of reference, whether or not vision is available.", "contents": "Voluntary, non-visual control of the human vestibulo-ocular reflex. Voluntary control of the human vestibulo-ocular reflex with and without visual targets was investigated. Subjects were rotated sinusoidally from 0.1 to 1.0 Hz using d.c. electro-oculography to record eye position. The ratio of eye to head movement, or gain, of the vestibulo-ocular reflex was measured. When subjects were rotated in the dark at 0.3 Hz whilst performing mental arithmetic the gain was 0.65. When subjects were asked to fixate imaginary targets in the dark that were stationary in space, the gain rose to 0.95. When they imagined targets rotating with them on the chair, the gain dropped to 0.35. Our results indicate that the ability to modulate the gain of the vestibulo-ocular reflex does not depend entirely on the smooth pursuit system. Higher centers must modulate eye velocity so that it is appropriate to the subject's choice of a frame of reference, whether or not vision is available."} {"id": "PMID:1274551", "title": "The effect of eye closure upon the pathological vestibular spontaneous nystagmus.", "content": "In the course of one year (September 1973 to September 1974) a total of 784 patients were examined with nystagmography. We were dealing with patients who consulted us for reasons of equilibrium disturbances, sensori-neural hearing loss and/or tinnitus. In 200 patients we observed a definite vestibular spontaneous nystagmus (SN) in supine position. Ocular pendular nystagmus was eliminated. On the basis of these 200 electronystagmographic recordings, the effect of eye closure upon the pathological spontaneous nystagmus was analysed. According to the statistical mean value, spontaneous nystagmus with open eyes in darkness was stimulated by eye closure. Further evaluation revealed, however, that 24% of our patients showed spontaneous nystagmus exclusively with open eyes in darkness, 30% only with closed eyes. Nevertheless, the occurrence of spontaneous nystagmus with either open or closed eyes in darkness, or in both conditions, does not permit topodiagnostic conclusions. The possibility of nystagmus inhibition by eye closure must be considered when the case history indicates a vestibular disturbance but a spontaneous nystagmus with closed eyes in absent in the electronystagmography. The clinical observations in one patient are described in detail for example. To exclude errors, one should search for a spontaneous nystagmus following the necessary examination behind Frenzel's glasses-in case of nystagmography-by closed as well as by opened eyes in darkness.", "contents": "The effect of eye closure upon the pathological vestibular spontaneous nystagmus. In the course of one year (September 1973 to September 1974) a total of 784 patients were examined with nystagmography. We were dealing with patients who consulted us for reasons of equilibrium disturbances, sensori-neural hearing loss and/or tinnitus. In 200 patients we observed a definite vestibular spontaneous nystagmus (SN) in supine position. Ocular pendular nystagmus was eliminated. On the basis of these 200 electronystagmographic recordings, the effect of eye closure upon the pathological spontaneous nystagmus was analysed. According to the statistical mean value, spontaneous nystagmus with open eyes in darkness was stimulated by eye closure. Further evaluation revealed, however, that 24% of our patients showed spontaneous nystagmus exclusively with open eyes in darkness, 30% only with closed eyes. Nevertheless, the occurrence of spontaneous nystagmus with either open or closed eyes in darkness, or in both conditions, does not permit topodiagnostic conclusions. The possibility of nystagmus inhibition by eye closure must be considered when the case history indicates a vestibular disturbance but a spontaneous nystagmus with closed eyes in absent in the electronystagmography. The clinical observations in one patient are described in detail for example. To exclude errors, one should search for a spontaneous nystagmus following the necessary examination behind Frenzel's glasses-in case of nystagmography-by closed as well as by opened eyes in darkness."} {"id": "PMID:1274555", "title": "Physiological and clinical aspects of the rehabilitation of total deafness by implantation of multiple intracochlear electrodes.", "content": "Many instances of total deafness are due to destruction of the organ of Corti, contrasting with the partial or complete preservation of the function of the cochlear nerve. In such cases, it is possible to restore some hearing by stimulating electrically the fibres of the cochlear nerve with the help of implanted electrodes. By means of several fenestrations, it is possible to construct electrically insulated compartments in the scala tympani of the cochlea, and to implant eight electrodes. This procedure allows discrimination of sound frequencies because the electrical stimulation of each electrode gives a sound sensation which depends on the electrode stimulated. This enabled us to elaborate a map of frequencies of the human cochlea and to make some physiological observations and achieve clinical results in seven cases of total bilateral deafness.", "contents": "Physiological and clinical aspects of the rehabilitation of total deafness by implantation of multiple intracochlear electrodes. Many instances of total deafness are due to destruction of the organ of Corti, contrasting with the partial or complete preservation of the function of the cochlear nerve. In such cases, it is possible to restore some hearing by stimulating electrically the fibres of the cochlear nerve with the help of implanted electrodes. By means of several fenestrations, it is possible to construct electrically insulated compartments in the scala tympani of the cochlea, and to implant eight electrodes. This procedure allows discrimination of sound frequencies because the electrical stimulation of each electrode gives a sound sensation which depends on the electrode stimulated. This enabled us to elaborate a map of frequencies of the human cochlea and to make some physiological observations and achieve clinical results in seven cases of total bilateral deafness."} {"id": "PMID:1274553", "title": "Damage to Reissner's membrane in the guinea-pig cochlea following acute atoxyl intoxication.", "content": "The ototoxic effects of the arsenic compound atoxyl has been earlier demonstrated by Anniko & Wers\u00e4ll (1975) in the stria vascularis of the guinea pig cochlea. The aim of the present investigation was to study the morphological degeneration at the ultrastructural level after damaging the Reissner's membrane experimentally. In acute atoxyl intoxication the first signs of degeneration appear after approximately 12 hours. After 24 hours, the membrane may be markedly degenerated. Both the epithelial and mesothelial cells become vacuolized, the mitochondria lose their internal structure and become swollen, and lipid granules are found in the cytoplasm. Mesothelial cells are damaged to a lesser extent than the epithelial cells in the same specimen.", "contents": "Damage to Reissner's membrane in the guinea-pig cochlea following acute atoxyl intoxication. The ototoxic effects of the arsenic compound atoxyl has been earlier demonstrated by Anniko & Wers\u00e4ll (1975) in the stria vascularis of the guinea pig cochlea. The aim of the present investigation was to study the morphological degeneration at the ultrastructural level after damaging the Reissner's membrane experimentally. In acute atoxyl intoxication the first signs of degeneration appear after approximately 12 hours. After 24 hours, the membrane may be markedly degenerated. Both the epithelial and mesothelial cells become vacuolized, the mitochondria lose their internal structure and become swollen, and lipid granules are found in the cytoplasm. Mesothelial cells are damaged to a lesser extent than the epithelial cells in the same specimen."} {"id": "PMID:1274556", "title": "Pressure-dependent variation in volume of mucosal lining of the middle ear.", "content": "A method is described for studying pressure-dependent variation in the volume of the mucosa of the middle ear. Studies were performed at different pressures in the middle ear as well as at different ambient pressures. It was found that the pressure-dependent volumetric changes of the mucosa were the same whether the pressure in the middle ear was changed directly by altering the intratympanic or indirectly by altering the ambient pressure. With the method described it is also possible to determine the middle ear volume without artefacts due to the middle ear mucosa. The volume-pressure relationship of the middle ear mucosa varied from 0.6 to 1.7 mul/cm H2O and linearly with the volume of the middle ear. Comparisons between determinations of the middle ear volume with and without consideration of the mucosal compliance showed differences, especially in small middle ears. The effect on the volume of the mucosa caused by variation of posture was also studied. The physiological middle ear pressure depends on the functional state of the Eustachian tube, the middle ear volume, the tympanic membrane and the middle ear mucosa. Thus, knowledge of the mucosa compliance is important for calculating middle ear pressure as well as for determining the volume of the air-filled middle ear space. The method might also prove a useful tool in the elucidation of the vascular bed both in health and in disease as well as the reaction of the mucosal vessels to drugs.", "contents": "Pressure-dependent variation in volume of mucosal lining of the middle ear. A method is described for studying pressure-dependent variation in the volume of the mucosa of the middle ear. Studies were performed at different pressures in the middle ear as well as at different ambient pressures. It was found that the pressure-dependent volumetric changes of the mucosa were the same whether the pressure in the middle ear was changed directly by altering the intratympanic or indirectly by altering the ambient pressure. With the method described it is also possible to determine the middle ear volume without artefacts due to the middle ear mucosa. The volume-pressure relationship of the middle ear mucosa varied from 0.6 to 1.7 mul/cm H2O and linearly with the volume of the middle ear. Comparisons between determinations of the middle ear volume with and without consideration of the mucosal compliance showed differences, especially in small middle ears. The effect on the volume of the mucosa caused by variation of posture was also studied. The physiological middle ear pressure depends on the functional state of the Eustachian tube, the middle ear volume, the tympanic membrane and the middle ear mucosa. Thus, knowledge of the mucosa compliance is important for calculating middle ear pressure as well as for determining the volume of the air-filled middle ear space. The method might also prove a useful tool in the elucidation of the vascular bed both in health and in disease as well as the reaction of the mucosal vessels to drugs."} {"id": "PMID:1274554", "title": "Effect of phlorizin on glucose transport in the inner ear.", "content": "14C-glucose was used as a tracer to study the effect of phlorizin on glucose transport into perilymph and endolymph. The transport was found to be lowered in phlorizin-injected animals compared with that in normal controls. This inhibitory effect corresponding to a phlorizin-sensitive part of glucose transport was greater in the perilymphatic system than in the endolymphatic system. Pathways which are not affected by phlorizin, are considered to exist in both compartments of perilymph and endolymph.", "contents": "Effect of phlorizin on glucose transport in the inner ear. 14C-glucose was used as a tracer to study the effect of phlorizin on glucose transport into perilymph and endolymph. The transport was found to be lowered in phlorizin-injected animals compared with that in normal controls. This inhibitory effect corresponding to a phlorizin-sensitive part of glucose transport was greater in the perilymphatic system than in the endolymphatic system. Pathways which are not affected by phlorizin, are considered to exist in both compartments of perilymph and endolymph."} {"id": "PMID:1274557", "title": "Dentine as an ossicular substitute. Experimental results in animals.", "content": "The fate of dentine grafts of autogenous, allogeneic and xenogeneic origin has been studied in rats both in muscle and in the middle ear. The dentine has been implanted fresh, autoclaved, Cialit-preserved and demineralised. Xenogeneic material tends to extrude from the ear and not to form a functional union with the structures it contacts. Fresh or Cialit-preserved, autogenous or allogeneic material, eventually stimulate new bone formation and usually become incorporated into the host ossicular chain; however, continuing resorptive activity is present. Autoclaved material does not result in new bone formation; demineralised allogeneic material stimulates very active new bone formation in the ossicular chain. It is concluded that non-demineralised dentine, on account of resorption, is inferior to ossicular grafts as a tympanoplastic material. Demineralised dentine, by virtue of its bone-inductive potential, may be of value in tympanoplasty.", "contents": "Dentine as an ossicular substitute. Experimental results in animals. The fate of dentine grafts of autogenous, allogeneic and xenogeneic origin has been studied in rats both in muscle and in the middle ear. The dentine has been implanted fresh, autoclaved, Cialit-preserved and demineralised. Xenogeneic material tends to extrude from the ear and not to form a functional union with the structures it contacts. Fresh or Cialit-preserved, autogenous or allogeneic material, eventually stimulate new bone formation and usually become incorporated into the host ossicular chain; however, continuing resorptive activity is present. Autoclaved material does not result in new bone formation; demineralised allogeneic material stimulates very active new bone formation in the ossicular chain. It is concluded that non-demineralised dentine, on account of resorption, is inferior to ossicular grafts as a tympanoplastic material. Demineralised dentine, by virtue of its bone-inductive potential, may be of value in tympanoplasty."} {"id": "PMID:1274558", "title": "Elimination of contrast medium from the maxillary sinus.", "content": "Drainage of contrast medium from the maxillary sinus during blowing and sniffing was studied by cine-roentgenography in 11 healthy subjects. The functional size of the maxillary ostium was measured by a manometric method. Sniffing facilitated drainage more than blowing but the effect was minimal for both procedures except when sniffing was performed with the head tilted to the side opposite the filled sinus. The latter procedures may trap air in the sinus above the level of the ostium and thus facilitate drainage during sniffing. Another facilitating factor which is discussed is that blowing the nose may catch tenacious mucus which has partly passed through the ostium by the ciliary activity in the sinus. The influence of the fluid viscosity is discussed. The time required for complete emptying of the sinus from contrast medium, studied over a period of several days, was found to be inversely correlated to the functional diameter of the maxillary ostium.", "contents": "Elimination of contrast medium from the maxillary sinus. Drainage of contrast medium from the maxillary sinus during blowing and sniffing was studied by cine-roentgenography in 11 healthy subjects. The functional size of the maxillary ostium was measured by a manometric method. Sniffing facilitated drainage more than blowing but the effect was minimal for both procedures except when sniffing was performed with the head tilted to the side opposite the filled sinus. The latter procedures may trap air in the sinus above the level of the ostium and thus facilitate drainage during sniffing. Another facilitating factor which is discussed is that blowing the nose may catch tenacious mucus which has partly passed through the ostium by the ciliary activity in the sinus. The influence of the fluid viscosity is discussed. The time required for complete emptying of the sinus from contrast medium, studied over a period of several days, was found to be inversely correlated to the functional diameter of the maxillary ostium."} {"id": "PMID:1274562", "title": "Respiratory function, cardiovascular dimensions and work capacity in boys with bronchial asthma.", "content": "Twenty boys with bronchial asthma, aged 8-13 years, were studied with regard to the size of their respiratory and circulatory organs and to their excercise tolerance. The boys were divided into two groups (A and B) depending on the severity of their subjective symptoms. Normal values were found for TLC, VC, and FRC in both groups, whereas the group with the most severe asthma had a slightly increased RV. In both groups THb, blood and heart volumes were normal. A quite normal relationship between these variables was observed as well as with work capacity (W170 and VO2 max) with no intergroup differences. Respiratory rate was lower and ventilation was increased in group B, both in submaximal and maximal exercise. Thus, tidal volume in maximal exercise exceeded 50 per cent of vital capacity in this group. These boys also had the highest blood lactate concentration at submaximal and maximal exercise. In half of the boys asthma-like attacks were elicited by the excercise. The symptoms subsided without treatment shortly after work. The frequency and intensity of attacks were similar in the two groups.", "contents": "Respiratory function, cardiovascular dimensions and work capacity in boys with bronchial asthma. Twenty boys with bronchial asthma, aged 8-13 years, were studied with regard to the size of their respiratory and circulatory organs and to their excercise tolerance. The boys were divided into two groups (A and B) depending on the severity of their subjective symptoms. Normal values were found for TLC, VC, and FRC in both groups, whereas the group with the most severe asthma had a slightly increased RV. In both groups THb, blood and heart volumes were normal. A quite normal relationship between these variables was observed as well as with work capacity (W170 and VO2 max) with no intergroup differences. Respiratory rate was lower and ventilation was increased in group B, both in submaximal and maximal exercise. Thus, tidal volume in maximal exercise exceeded 50 per cent of vital capacity in this group. These boys also had the highest blood lactate concentration at submaximal and maximal exercise. In half of the boys asthma-like attacks were elicited by the excercise. The symptoms subsided without treatment shortly after work. The frequency and intensity of attacks were similar in the two groups."} {"id": "PMID:1274559", "title": "The role of psychic factors in patients with allergic rhinitis.", "content": "Psychosomatic studies were made in 128 patients with allergic rhinitis. After the allergic and clinical anamnesis the patients were divided into two groups: those ill with hay fever (91 patients) and those suffering from perennial allergic rhinitis (37 patients). The assessment of the role of psychogenous factors in both varieties of allergic rhinitis was the main purpose of the investigation. The investigation showed that psychogenous factors are practically of no importance in hay fevers. Their role is great, however, when perennial allergic rhinitis is involved.", "contents": "The role of psychic factors in patients with allergic rhinitis. Psychosomatic studies were made in 128 patients with allergic rhinitis. After the allergic and clinical anamnesis the patients were divided into two groups: those ill with hay fever (91 patients) and those suffering from perennial allergic rhinitis (37 patients). The assessment of the role of psychogenous factors in both varieties of allergic rhinitis was the main purpose of the investigation. The investigation showed that psychogenous factors are practically of no importance in hay fevers. Their role is great, however, when perennial allergic rhinitis is involved."} {"id": "PMID:1274563", "title": "Gluconeogenesis in infancy and childhood. II. Studies on the glucose production from alanine in three cases of persistent neonatal hypoglycaemia.", "content": "Gluconeogenesis was studied in 3 cases of persistent neonatal hypoglycaemia. In 2 of the cases the labelling of blood glucose after i.v. injection of 1415C-alanine was reduced. In these 2 patients only 1.3-5% of the injected radioactivity was recovered in blood glucose, compared with 10% in normoglycaemic patients. The labelling of glucose from 14C-glycerol, as studied in one case, was not reduced. In this patient the labelling of blood glucose from C-alanine was improved after subtotal resection of the pancreas, and with increasing age. By the time of the isotope studies the plasma insulin was normal in all patients, and no deficiency of glucagon secretion could be detected after stimulation with an alanine load. A quantitative amino acid analysis of plasma revealed a moderate increase of some of the glucogenic amino acids. The results were interpreted as a deficiency of gluconeogenesis, probably at the phosphoenolpyruvate carboxykinase or pyruvate carboxylase step.", "contents": "Gluconeogenesis in infancy and childhood. II. Studies on the glucose production from alanine in three cases of persistent neonatal hypoglycaemia. Gluconeogenesis was studied in 3 cases of persistent neonatal hypoglycaemia. In 2 of the cases the labelling of blood glucose after i.v. injection of 1415C-alanine was reduced. In these 2 patients only 1.3-5% of the injected radioactivity was recovered in blood glucose, compared with 10% in normoglycaemic patients. The labelling of glucose from 14C-glycerol, as studied in one case, was not reduced. In this patient the labelling of blood glucose from C-alanine was improved after subtotal resection of the pancreas, and with increasing age. By the time of the isotope studies the plasma insulin was normal in all patients, and no deficiency of glucagon secretion could be detected after stimulation with an alanine load. A quantitative amino acid analysis of plasma revealed a moderate increase of some of the glucogenic amino acids. The results were interpreted as a deficiency of gluconeogenesis, probably at the phosphoenolpyruvate carboxykinase or pyruvate carboxylase step."} {"id": "PMID:1274560", "title": "A cytochemical method of grading the malignancy of salivary gland tumours preoperatively.", "content": "Aspiration biopsy is an accurate but still a somewhat controversial method of diagnosing salivary gland tumours preoperatively. During the last few years this method has been more and more accepted dependent on its increasing reliability in diagnosing the different types of tumours, but for an adequate treatment it is also important to know the malignancy degree of the individual tumour. Since invasiveness is the most significant morphological criterion in evaluating the prognosis of a salivary gland tumour it has, however, been difficult to grade the malignancy morphologically on a cytological basis. Thus the diagnostic value of the aspiration biopsy method would increase, if beside the morphological determination of the tumour type it was possible to find a cellular criterion which reflects the grade of malignancy. In the present investigation we have studied the nuclear DNA content in non-invasive tumours and invasive tumours. In general, invasive tumours were characterized by a higher degree of abnormality with respect to the DNA content than the non-invasive tumours. In two tumour types especially studied-mucoepidermoid carcinoma and acinic cell carcinoma-the property of non-invasive growth was found to be associated with a diploid or near-diploid DNA content, whereas invasive growth was associated with a triploid or near-triploid DNA content. These data suggest that the nuclear DNA Content may be related to the morphological differentiation and particularly to the invasive properties of the salivary gland tumours. Thus, cytophotometric DNA analysis of DNA content in the smears from aspirates might be valuable in grading the malignancy of the tumours preoperatively by aspiration biopsy.", "contents": "A cytochemical method of grading the malignancy of salivary gland tumours preoperatively. Aspiration biopsy is an accurate but still a somewhat controversial method of diagnosing salivary gland tumours preoperatively. During the last few years this method has been more and more accepted dependent on its increasing reliability in diagnosing the different types of tumours, but for an adequate treatment it is also important to know the malignancy degree of the individual tumour. Since invasiveness is the most significant morphological criterion in evaluating the prognosis of a salivary gland tumour it has, however, been difficult to grade the malignancy morphologically on a cytological basis. Thus the diagnostic value of the aspiration biopsy method would increase, if beside the morphological determination of the tumour type it was possible to find a cellular criterion which reflects the grade of malignancy. In the present investigation we have studied the nuclear DNA content in non-invasive tumours and invasive tumours. In general, invasive tumours were characterized by a higher degree of abnormality with respect to the DNA content than the non-invasive tumours. In two tumour types especially studied-mucoepidermoid carcinoma and acinic cell carcinoma-the property of non-invasive growth was found to be associated with a diploid or near-diploid DNA content, whereas invasive growth was associated with a triploid or near-triploid DNA content. These data suggest that the nuclear DNA Content may be related to the morphological differentiation and particularly to the invasive properties of the salivary gland tumours. Thus, cytophotometric DNA analysis of DNA content in the smears from aspirates might be valuable in grading the malignancy of the tumours preoperatively by aspiration biopsy."} {"id": "PMID:1274564", "title": "Human adipose tissue in culture. VI. Effect of age on cell size and lipolysis.", "content": "Biopsies of subcutaneous adipose tissue were taken from children varying in age from a few hours to 15 years. In 63 children the cell diameter was determined. Weight in relation to height was normal. At an average the fat cell weight was 0.05 mug in the new-born, but adolescent values were reached within the first year of life. Biopsies from 23 children were incubated for one week in vitro. Cell size was not changed significantly during this period. Glycerol release was strongly correlated to cell size and the long-term effect of insulin on the lipolysis was found to be stimulating as previously shown for adults. At the same cell size basal lipolysis was higher in children below one year of age than later in life. It is concluded that the tissue culture method may be used for studies of adopose tissue from children. Furthermore, the data indicate that there is a difference in adipose tissue metabolism and cell size of children below one year as compared to older children and adults.", "contents": "Human adipose tissue in culture. VI. Effect of age on cell size and lipolysis. Biopsies of subcutaneous adipose tissue were taken from children varying in age from a few hours to 15 years. In 63 children the cell diameter was determined. Weight in relation to height was normal. At an average the fat cell weight was 0.05 mug in the new-born, but adolescent values were reached within the first year of life. Biopsies from 23 children were incubated for one week in vitro. Cell size was not changed significantly during this period. Glycerol release was strongly correlated to cell size and the long-term effect of insulin on the lipolysis was found to be stimulating as previously shown for adults. At the same cell size basal lipolysis was higher in children below one year of age than later in life. It is concluded that the tissue culture method may be used for studies of adopose tissue from children. Furthermore, the data indicate that there is a difference in adipose tissue metabolism and cell size of children below one year as compared to older children and adults."} {"id": "PMID:1274565", "title": "Sequential determination of C-reactive protein in acute childhood pyelonephritis.", "content": "Serum CRP levels ranging between 10 and 200 mug/ml were found in 19 patients with acute pyelonephritis. Treatment with antibacterial drugs, to which the bacteria were fully sensitive, resulted in a rapid decrease of the CRP values and very low or trace amounts were attained within a week. In contrast, cases ineffectively treated and/or reinfected showed increasing or slowly decreasing CRP levels. It is suggested that repeated CRP determinations can be used as a diagnostic tool for the rapid detection of cases of acute pyelonephritis in which treatment is ineffective.", "contents": "Sequential determination of C-reactive protein in acute childhood pyelonephritis. Serum CRP levels ranging between 10 and 200 mug/ml were found in 19 patients with acute pyelonephritis. Treatment with antibacterial drugs, to which the bacteria were fully sensitive, resulted in a rapid decrease of the CRP values and very low or trace amounts were attained within a week. In contrast, cases ineffectively treated and/or reinfected showed increasing or slowly decreasing CRP levels. It is suggested that repeated CRP determinations can be used as a diagnostic tool for the rapid detection of cases of acute pyelonephritis in which treatment is ineffective."} {"id": "PMID:1274566", "title": "The effect of early diagnosis of congenital dislocation of the hip.", "content": "The effects of early diagnostic measures of congenital dislocation of the hip (CDH) in Malm\u00f6 during the years 1956-1972 were investigated. Of 58759 newborns 548 were diagnosed as having CDH. Only 4 cases were missed at the initial examination. Thus, all, or almost all, children with CDH can be diagnosed at birth provided that the initial examination is undertaken within 24 or 48 hours.", "contents": "The effect of early diagnosis of congenital dislocation of the hip. The effects of early diagnostic measures of congenital dislocation of the hip (CDH) in Malm\u00f6 during the years 1956-1972 were investigated. Of 58759 newborns 548 were diagnosed as having CDH. Only 4 cases were missed at the initial examination. Thus, all, or almost all, children with CDH can be diagnosed at birth provided that the initial examination is undertaken within 24 or 48 hours."} {"id": "PMID:1274567", "title": "Dietary effects in the early recovery phase of kwashiorkor. Plasma levels of triglycerides, FFA, D-beta-hydroxybutyrate, glycerol, postheparin lipoprotein lipase (LPL), glucose and insulin.", "content": "The fatty liver often found in untreated kwashiorkor has been associated with highly variable concentration of circulating lipids. The effect on lipid metabolism of two isocaloric diets--one synthetic monomolecular (Vivonex) and one standard (Casilan)--which both initiated satisfactory clinical improvement was studied in 21 Ethiopian children with kwashiorkor during the first weeks of rehabilitation. Before treatment mean fasting values of all biochemical parameters were within normal ranges except for moderately elevated triglycerides--an unexpected finding-and low insulin. Individual values varied greatly; triglyceride between 0.39 and 3.49 mmol/1. FFA correlated both to glycerol, D-beta-hydroxybutyrate and triglyceride values. During treatment insulin, glucose and glycerol remained essentially unchanged and were similar in both dietary groups. In the Vivonex group only there was an initial marked, parallel fall of FFA and D-beta-hydroxybutyrate suggesting greater availability of carbohydrate and enhanced glucose utilization. This pattern of response seemed to occur without comparable inhibition of lipolysis. Triglycerides--like serum albumin--increased faster in the Casilan group. The highest mean triglyceride value was reached by day 8 in the Casilan group and by day 15 in the Vivonex group. Ten minutes following heparin injection triglycerides declined, FFA and glycerol increased indicating release of in vivo active lipase. LPL activity assayed in vitro was similar and unaffected by 2 weeks of dietary treatment in both groups. LPL activity was inversely correlated to triglycerides providing--beside the type of diet--another possible explanation for the wide variations seen in circulatory triglycerides.", "contents": "Dietary effects in the early recovery phase of kwashiorkor. Plasma levels of triglycerides, FFA, D-beta-hydroxybutyrate, glycerol, postheparin lipoprotein lipase (LPL), glucose and insulin. The fatty liver often found in untreated kwashiorkor has been associated with highly variable concentration of circulating lipids. The effect on lipid metabolism of two isocaloric diets--one synthetic monomolecular (Vivonex) and one standard (Casilan)--which both initiated satisfactory clinical improvement was studied in 21 Ethiopian children with kwashiorkor during the first weeks of rehabilitation. Before treatment mean fasting values of all biochemical parameters were within normal ranges except for moderately elevated triglycerides--an unexpected finding-and low insulin. Individual values varied greatly; triglyceride between 0.39 and 3.49 mmol/1. FFA correlated both to glycerol, D-beta-hydroxybutyrate and triglyceride values. During treatment insulin, glucose and glycerol remained essentially unchanged and were similar in both dietary groups. In the Vivonex group only there was an initial marked, parallel fall of FFA and D-beta-hydroxybutyrate suggesting greater availability of carbohydrate and enhanced glucose utilization. This pattern of response seemed to occur without comparable inhibition of lipolysis. Triglycerides--like serum albumin--increased faster in the Casilan group. The highest mean triglyceride value was reached by day 8 in the Casilan group and by day 15 in the Vivonex group. Ten minutes following heparin injection triglycerides declined, FFA and glycerol increased indicating release of in vivo active lipase. LPL activity assayed in vitro was similar and unaffected by 2 weeks of dietary treatment in both groups. LPL activity was inversely correlated to triglycerides providing--beside the type of diet--another possible explanation for the wide variations seen in circulatory triglycerides."} {"id": "PMID:1274568", "title": "The role of cathepsin D in pathogenesis of acute post-streptococcal glomerulonephritis.", "content": "Cathepsin D activity has been studied by a fluoremetric assay in the urine of acute post-streptococcal glomerulonephritic (APSGN) patients aged from 3 to 14 years and has been found elevated when compared with four groups of controls. This activity cannot be accounted for by erythrocytes and/or leukocytes in the urine of these patients since haematuric and pyuric controls did not exhibit an amount of enzyme activity greater than the normal control group. Cathepsin D activity can be attributed to lysosomal enzymes released from polymorphonuclear leukocytes which are in close contact with glomerular basement membrane. Complement C3 levels in serum and cathepsin D activity in urine of these patients showed no correlation.", "contents": "The role of cathepsin D in pathogenesis of acute post-streptococcal glomerulonephritis. Cathepsin D activity has been studied by a fluoremetric assay in the urine of acute post-streptococcal glomerulonephritic (APSGN) patients aged from 3 to 14 years and has been found elevated when compared with four groups of controls. This activity cannot be accounted for by erythrocytes and/or leukocytes in the urine of these patients since haematuric and pyuric controls did not exhibit an amount of enzyme activity greater than the normal control group. Cathepsin D activity can be attributed to lysosomal enzymes released from polymorphonuclear leukocytes which are in close contact with glomerular basement membrane. Complement C3 levels in serum and cathepsin D activity in urine of these patients showed no correlation."} {"id": "PMID:1274569", "title": "The role of haemolysis in neonatal hyperbilirubinaemia as reflected in carboxyhaemoglobin levels.", "content": "Carboxyhaemoglobin levels were measured in 250 consecutive, normal, term newborns and in a group of 75 severely jaundiced infants in an effort to assess the role of haemolysis in non-specific neonatal hyperbilirubinaemia--\"Physiologic jaundice\"-as well as in severe jaundice of various etiologies. In normal newborns a significant correlation (r=0.3293, p less than 0.001) was found between third-day carboxyhaemoglobin and serum bilirubin levels. Significant correlations were also found between the cord and third day values for carboxyhaemoglobin (infants of non-smoking mothers) for reticulocyte count, and for serum bilirubin. Third day haemoglobin showed no correlation with any of the other parameters including cord haemoglobin. Of the infants with third day carboxyhaemoglobin up to 0.75%, 1.7% had third day serum bilirubin values above 16.0 mg/100 ml. The corresponding percentage for the infants with carboxyhaemoglobin above 0.75% was 6.1%. It is concluded that increased rates of haemolysis due to as yet unspecified caused play an important role in the non-specific hyperbilirubinaemia of normal term newborns. As expected, high levels of carboxyhaemoglobin were found in infants with severe jaundice due to Rhesus and ABO haemolytic disease and glucose-6-phosphate dehydrogenase deficiency but also in jaundiced prematures and in Greek infants with severe jaundice of unknown cause.", "contents": "The role of haemolysis in neonatal hyperbilirubinaemia as reflected in carboxyhaemoglobin levels. Carboxyhaemoglobin levels were measured in 250 consecutive, normal, term newborns and in a group of 75 severely jaundiced infants in an effort to assess the role of haemolysis in non-specific neonatal hyperbilirubinaemia--\"Physiologic jaundice\"-as well as in severe jaundice of various etiologies. In normal newborns a significant correlation (r=0.3293, p less than 0.001) was found between third-day carboxyhaemoglobin and serum bilirubin levels. Significant correlations were also found between the cord and third day values for carboxyhaemoglobin (infants of non-smoking mothers) for reticulocyte count, and for serum bilirubin. Third day haemoglobin showed no correlation with any of the other parameters including cord haemoglobin. Of the infants with third day carboxyhaemoglobin up to 0.75%, 1.7% had third day serum bilirubin values above 16.0 mg/100 ml. The corresponding percentage for the infants with carboxyhaemoglobin above 0.75% was 6.1%. It is concluded that increased rates of haemolysis due to as yet unspecified caused play an important role in the non-specific hyperbilirubinaemia of normal term newborns. As expected, high levels of carboxyhaemoglobin were found in infants with severe jaundice due to Rhesus and ABO haemolytic disease and glucose-6-phosphate dehydrogenase deficiency but also in jaundiced prematures and in Greek infants with severe jaundice of unknown cause."} {"id": "PMID:1274570", "title": "Treatment of idiopathic autoimmune hemolytic anemia in children. Review and report of two fatal cases in infancy.", "content": "Report of two cases of severe idiopathic autoimmune hemolytic anemia (AIHA) in infants who underwent splenectomy and received corticosteroids and cyclophosphamide without benefit. One infant, additionally, was treated with thymectomy and azathioprine without influencing his disease. Experience of therapy for childhood AIHA is reviewed. Four children with AIHA have been thymectomized. Two of these failed to benefit from surgery. There have been fifteen previous trials with immunosuppressive agents in childhood AIHA. About 60% of the children so treated (9 of 15) have shown improvement. Additional clinical trials with this agent are warranted.", "contents": "Treatment of idiopathic autoimmune hemolytic anemia in children. Review and report of two fatal cases in infancy. Report of two cases of severe idiopathic autoimmune hemolytic anemia (AIHA) in infants who underwent splenectomy and received corticosteroids and cyclophosphamide without benefit. One infant, additionally, was treated with thymectomy and azathioprine without influencing his disease. Experience of therapy for childhood AIHA is reviewed. Four children with AIHA have been thymectomized. Two of these failed to benefit from surgery. There have been fifteen previous trials with immunosuppressive agents in childhood AIHA. About 60% of the children so treated (9 of 15) have shown improvement. Additional clinical trials with this agent are warranted."} {"id": "PMID:1274571", "title": "Familial occurrence of cerebral gigantism, Sotos' syndrome.", "content": "Since the original description of cerebral gigantism, about 85 cases have been reported. Four papers comment on familial occurrence but never in parents and their children. This paper describes the syndrome in a mother and her child, which, together with facts pointing towards prenatal etiology, such as excessive birthweight, striking mutual resemblance and abnormal dermatoglyphics, points to a genetic defect. Previous endocrine studies are enlarged by the findings of normal serum somatomedin and serum prolactin.", "contents": "Familial occurrence of cerebral gigantism, Sotos' syndrome. Since the original description of cerebral gigantism, about 85 cases have been reported. Four papers comment on familial occurrence but never in parents and their children. This paper describes the syndrome in a mother and her child, which, together with facts pointing towards prenatal etiology, such as excessive birthweight, striking mutual resemblance and abnormal dermatoglyphics, points to a genetic defect. Previous endocrine studies are enlarged by the findings of normal serum somatomedin and serum prolactin."} {"id": "PMID:1274572", "title": "Unstable-haemoglobin haemolytic anaemia.", "content": "A 6-year-old girl suffering from chronic haemolytic anaemia with crisis induced by drugs and infections is described. The disorder was diagnosed as an unstable-haemoglobin haemolytic anaemia. The heat stability test, simple and specific for unstable haemoglobins is mentioned, it should be done in every child suffering from unexplained chronic haemolytic anaemia. The haemoglobin variant is also known in a patient in Brazil as Hb Niteroi.", "contents": "Unstable-haemoglobin haemolytic anaemia. A 6-year-old girl suffering from chronic haemolytic anaemia with crisis induced by drugs and infections is described. The disorder was diagnosed as an unstable-haemoglobin haemolytic anaemia. The heat stability test, simple and specific for unstable haemoglobins is mentioned, it should be done in every child suffering from unexplained chronic haemolytic anaemia. The haemoglobin variant is also known in a patient in Brazil as Hb Niteroi."} {"id": "PMID:1274573", "title": "An ultrastructural study on precancerous and cancerous lesions of the glandular stomach in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine.", "content": "Electron microscopic study was made on precancerous and cancerous lesions in glandular stomach of rats induced by MNNG. Three types of lesions, were found: regenerative glandular hyperplasia, adenomatous hyperplasia and adenocarcinoma. These were compared with the fine structure of similar lesions produced by X-irradiation in the glandular stomach of mice. The precancerous lesion in the present study demonstrated formation of adenomatous hyperplasia by epithelial cells which included mucoid cells characterized by sparce surface microvilli, a few erratic terminal webs, small number of mucous granules, many small mitochondria, and a bizarre nucleus. The development of these mucoid cells seems to be related with the growth of gastric carcinoma. The ultrastructure of adenocarcinomas revealed many structural variations or abnormalities of cellular differentiation. They were classified into 1) surface and pit mucous cell type, 2) pyloric gland cell type, 3) goblet cell type, 4) paneth cell type, 5) intestinal epithelial cell type, 6) endocrine cell type, 7) oncocyte type, 8) filament-rich cell type, and 9) anaplastic cell type involving intracellular microcyst cells. Filament-rich cells were found in poorly differentiated adenocarcinoma or scirrhous carcinoma and may be derived from metaplasia of tumor cell.", "contents": "An ultrastructural study on precancerous and cancerous lesions of the glandular stomach in rats induced by N-methyl-N'-nitro-N-nitrosoguanidine. Electron microscopic study was made on precancerous and cancerous lesions in glandular stomach of rats induced by MNNG. Three types of lesions, were found: regenerative glandular hyperplasia, adenomatous hyperplasia and adenocarcinoma. These were compared with the fine structure of similar lesions produced by X-irradiation in the glandular stomach of mice. The precancerous lesion in the present study demonstrated formation of adenomatous hyperplasia by epithelial cells which included mucoid cells characterized by sparce surface microvilli, a few erratic terminal webs, small number of mucous granules, many small mitochondria, and a bizarre nucleus. The development of these mucoid cells seems to be related with the growth of gastric carcinoma. The ultrastructure of adenocarcinomas revealed many structural variations or abnormalities of cellular differentiation. They were classified into 1) surface and pit mucous cell type, 2) pyloric gland cell type, 3) goblet cell type, 4) paneth cell type, 5) intestinal epithelial cell type, 6) endocrine cell type, 7) oncocyte type, 8) filament-rich cell type, and 9) anaplastic cell type involving intracellular microcyst cells. Filament-rich cells were found in poorly differentiated adenocarcinoma or scirrhous carcinoma and may be derived from metaplasia of tumor cell."} {"id": "PMID:1274574", "title": "Abnormal intracranial vascular networks (\"moyamoya\" disease), possibly due to occlusion of bilateral internal carotid arteries--a case report with histometrical analysis.", "content": "An autopsy case of abnormal intracranial vascular networks at the base of the brain corresponding to so-called rete mirabile, associated with occlusion of bilateral internal carotid arteries was reported. This patient was a 62 year-old female who died about two months after sudden onset of subarachnoid hemorrhage. At autopsy, abnormal vascular networks termed as rete mirabile were observed to be collateral blood supplies among the cerebral regions with flow of the anterior, middle, and posterior cerebral arteries, caused by long-standing obstruction of bilateral internal carotid arteries at the syphon level. Morphometrical analysis was done by measuring the length of internal elastic membrane of the internal carotid arteries in cross section, and comparing it with those of controlled persons of the same sex and age without any intracranial disorders and hypertensive histories. The result that no significant difference was observed between the former and the latter values suggested that the unusual cerebro-vascular disorder of this case developed not on the base of congenital anomaly including hypoplasia of internal carotid arteries or arteriovenous malformation but as an acquired lesion established for a long time.", "contents": "Abnormal intracranial vascular networks (\"moyamoya\" disease), possibly due to occlusion of bilateral internal carotid arteries--a case report with histometrical analysis. An autopsy case of abnormal intracranial vascular networks at the base of the brain corresponding to so-called rete mirabile, associated with occlusion of bilateral internal carotid arteries was reported. This patient was a 62 year-old female who died about two months after sudden onset of subarachnoid hemorrhage. At autopsy, abnormal vascular networks termed as rete mirabile were observed to be collateral blood supplies among the cerebral regions with flow of the anterior, middle, and posterior cerebral arteries, caused by long-standing obstruction of bilateral internal carotid arteries at the syphon level. Morphometrical analysis was done by measuring the length of internal elastic membrane of the internal carotid arteries in cross section, and comparing it with those of controlled persons of the same sex and age without any intracranial disorders and hypertensive histories. The result that no significant difference was observed between the former and the latter values suggested that the unusual cerebro-vascular disorder of this case developed not on the base of congenital anomaly including hypoplasia of internal carotid arteries or arteriovenous malformation but as an acquired lesion established for a long time."} {"id": "PMID:1274575", "title": "Ultrastructure of the giant cell in de Quervain's subacute thyroiditis.", "content": "The author made an electron microscopic observation on multinucleated giant cells which appear in the thyroid gland in subacute thyroiditis (de Quervain). Numerous typical desmosomes, which intermingled with myriad of mitochondria and small electron dense granules, were found in the cytoplasm of giant cell. Desmosome is one peculiar to the intercellular junction of follicular epithelium of the thyroid gland, and the fact that many desmosomes were found in the cytoplasm is one of the proofs showing this giant cell to be possibly derived from the follicular epithelium.", "contents": "Ultrastructure of the giant cell in de Quervain's subacute thyroiditis. The author made an electron microscopic observation on multinucleated giant cells which appear in the thyroid gland in subacute thyroiditis (de Quervain). Numerous typical desmosomes, which intermingled with myriad of mitochondria and small electron dense granules, were found in the cytoplasm of giant cell. Desmosome is one peculiar to the intercellular junction of follicular epithelium of the thyroid gland, and the fact that many desmosomes were found in the cytoplasm is one of the proofs showing this giant cell to be possibly derived from the follicular epithelium."} {"id": "PMID:1274576", "title": "Histological study on the numerical change of plasma cells in regional lymph nodes of the carcinomatous stomach.", "content": "The relationship between metastatic lesions and the degree of appearance of plasma cells in regional lymph nodes affected by carcinoma of the stomach was observed in this study. At the initial stage of metastasis to a lymph node, numerous plasma cells were found in tje lymphatic parenchyma adjacent to the metastatic lesion. As the metastatic lesions increased, the number of plasma cells decreased. Few plasma cells appeared in the intact lymph node distant from the primary lesion of carcinoma. It is suspected that this phenomenon may be tentatively explicable from the antigen-antibody reaction at the initial stage of metastasis in a lymph node.", "contents": "Histological study on the numerical change of plasma cells in regional lymph nodes of the carcinomatous stomach. The relationship between metastatic lesions and the degree of appearance of plasma cells in regional lymph nodes affected by carcinoma of the stomach was observed in this study. At the initial stage of metastasis to a lymph node, numerous plasma cells were found in tje lymphatic parenchyma adjacent to the metastatic lesion. As the metastatic lesions increased, the number of plasma cells decreased. Few plasma cells appeared in the intact lymph node distant from the primary lesion of carcinoma. It is suspected that this phenomenon may be tentatively explicable from the antigen-antibody reaction at the initial stage of metastasis in a lymph node."} {"id": "PMID:1274577", "title": "A histopathological study on diabetic nephropathy -- light and electron microscopic observations.", "content": "A historical review and the present author's study on diabetic nephropathy have been presented. Three characteristic lesions in KW-lesion, namely nodular, exudative and doughnut lesion may all be regarded as to be caused by severe circulatory disturbance occurring in intraglomerular branches of the afferent artery. This circulatory disturbance is considered to be brought about by sudden spasm of the peripheral portion of the afferent branches. The diffuse form of Bell may be regarded as to be a slighter type without severe mesangiolysis. Arteriolar hyalinosis and arteriosclerosis and/or atherosclerosis may be caused by intraglomerular circulatory disturbances. The most important problem in diabetic nephropathy, including KW-lesion and Bell's diffuse form, is to elucidate the mechanism leading to the occurrence of spasm of the peripheral portion of intraglomerular afferent branches. Becker found fixation of antiactomyosin-antibody in the mesangial tissue by the immunofluorescent method. Many studies along this line have been made, but none are adequate in fully explaining the mechanism involved.", "contents": "A histopathological study on diabetic nephropathy -- light and electron microscopic observations. A historical review and the present author's study on diabetic nephropathy have been presented. Three characteristic lesions in KW-lesion, namely nodular, exudative and doughnut lesion may all be regarded as to be caused by severe circulatory disturbance occurring in intraglomerular branches of the afferent artery. This circulatory disturbance is considered to be brought about by sudden spasm of the peripheral portion of the afferent branches. The diffuse form of Bell may be regarded as to be a slighter type without severe mesangiolysis. Arteriolar hyalinosis and arteriosclerosis and/or atherosclerosis may be caused by intraglomerular circulatory disturbances. The most important problem in diabetic nephropathy, including KW-lesion and Bell's diffuse form, is to elucidate the mechanism leading to the occurrence of spasm of the peripheral portion of intraglomerular afferent branches. Becker found fixation of antiactomyosin-antibody in the mesangial tissue by the immunofluorescent method. Many studies along this line have been made, but none are adequate in fully explaining the mechanism involved."} {"id": "PMID:1274578", "title": "Inhibition of senile amyloidosis of mice by biscarboxyethyl germanium sesqui-oxide.", "content": "A mouse strain, ICR/SLC, was involved in spontaneous amyloidosis with high incidence. The amyloid deposition in this strain was seen mainly in the mucosal propria of duodenum and terminal ileum, liver, spleen, adrenal cortices, and renal glomeruli. The mice, orally administered more than 300 mg/kg of organic germanium for 22 months since 5 weeks old, did not develop amyloidosis. Half of the mice, given 30 mg/kg of organic germanium for 22 months developed amyloidosis. The mice given 5% carboxymethylcellulose, the solvent of organic germanium, were affected with systemic amyloidosis with high frequency. The results showed that the organic germanium successfully inhibited the occurrence of senile amyloidosis with dose response. The agent did not have any apparent relation to the incidence of hepatic cell carcinoma or pulmonary adenoma which is frequently combined with aged mice. Although the actual mechanism involved is not clear, the evidence of the inhibition of senile amyloidosis by organic germanium may give a light to elucidate the pathogenesis of amyloidosis.", "contents": "Inhibition of senile amyloidosis of mice by biscarboxyethyl germanium sesqui-oxide. A mouse strain, ICR/SLC, was involved in spontaneous amyloidosis with high incidence. The amyloid deposition in this strain was seen mainly in the mucosal propria of duodenum and terminal ileum, liver, spleen, adrenal cortices, and renal glomeruli. The mice, orally administered more than 300 mg/kg of organic germanium for 22 months since 5 weeks old, did not develop amyloidosis. Half of the mice, given 30 mg/kg of organic germanium for 22 months developed amyloidosis. The mice given 5% carboxymethylcellulose, the solvent of organic germanium, were affected with systemic amyloidosis with high frequency. The results showed that the organic germanium successfully inhibited the occurrence of senile amyloidosis with dose response. The agent did not have any apparent relation to the incidence of hepatic cell carcinoma or pulmonary adenoma which is frequently combined with aged mice. Although the actual mechanism involved is not clear, the evidence of the inhibition of senile amyloidosis by organic germanium may give a light to elucidate the pathogenesis of amyloidosis."} {"id": "PMID:1274579", "title": "The role of coagulation and fibrinolysis in the development of rabbit Masugi nephritis.", "content": "The role of coagulation and fibrinolysis in the pathogenesis of rabbit Masugi nephritis was studied. Fibrinolytic activity of urine decreased rapidly to the minimum values at the peak of the disease. Histologic observations showed a severe proliferative glomerulonephritis. Immunofluorescent studies revealed localization of rabbit gamma globulin along the glomerular basement membrane in a typical linear pattern. Fibrin was positive in glomeruli not only within fibrinoid deposits, but also often diffusely in the places where no obvious fibrin was detected in histologic sections. Bright strands of fibrin was present between the cells forming a cresent. Electron microscopy indicated accumulation of fibrinoid materials beneath the endothelium. The basement membrane was damaged by the deposition of fibrinoid and followed by massive escape of intracapillary contents into the Bowman's space. Abundant fibrin and fibrinoid were seen in newly formed \"monocytic-epithelial\" crescents. Todd's fibrinolysis autography revealed diminished fibrinolytic activity in the severely affected glomeruli. Treatment with heparin prevented crescent formation and glomerular disorganization, while treatment with t-AMCHA increased fibrin and fibrinoid deposition and aggravated the glomerular injuries. It was concluded that the coagulation-fibrinolysis system could play an important role in the course of rabbit Masugi nephritis.", "contents": "The role of coagulation and fibrinolysis in the development of rabbit Masugi nephritis. The role of coagulation and fibrinolysis in the pathogenesis of rabbit Masugi nephritis was studied. Fibrinolytic activity of urine decreased rapidly to the minimum values at the peak of the disease. Histologic observations showed a severe proliferative glomerulonephritis. Immunofluorescent studies revealed localization of rabbit gamma globulin along the glomerular basement membrane in a typical linear pattern. Fibrin was positive in glomeruli not only within fibrinoid deposits, but also often diffusely in the places where no obvious fibrin was detected in histologic sections. Bright strands of fibrin was present between the cells forming a cresent. Electron microscopy indicated accumulation of fibrinoid materials beneath the endothelium. The basement membrane was damaged by the deposition of fibrinoid and followed by massive escape of intracapillary contents into the Bowman's space. Abundant fibrin and fibrinoid were seen in newly formed \"monocytic-epithelial\" crescents. Todd's fibrinolysis autography revealed diminished fibrinolytic activity in the severely affected glomeruli. Treatment with heparin prevented crescent formation and glomerular disorganization, while treatment with t-AMCHA increased fibrin and fibrinoid deposition and aggravated the glomerular injuries. It was concluded that the coagulation-fibrinolysis system could play an important role in the course of rabbit Masugi nephritis."} {"id": "PMID:1274580", "title": "Ultrastructure of the \"non-pathologic\" human pituitary gland.", "content": "The ultrastructure of \"non-pathologic\" human pituitary gland obtained from eight cases at autopsy, who received no hormonal therapy and who revealed no significant changes in the pituitary and its target organs, was investigated in an attempt to identify human adenohypophyseal cells by comparing their secretory granules with those of experimental animals. Besides the follicular cell, five different granulated cell types were distinguished The Type 1 cell contained abundant, dense secretory granules (350-500 mmu across). The Type II cell was characterized by dense granules, which were the largest in size (500-700 mmu across) and the most irregular in shape. Granules of the Type III cell were less characteristic (200-300 mmu across). The Type IV cell contained dense granules, which were the smallest in size (100-150 mmu across) and were characteristically arranged along the plasma membrane. The Type V cell was characterized by the presence of small, haloed granules (100-200 mmu across). The cells of these five types could presumably be the somatotroph, lactotroph, gonadotroph, thyrotroph and corcitotroph, respectively.", "contents": "Ultrastructure of the \"non-pathologic\" human pituitary gland. The ultrastructure of \"non-pathologic\" human pituitary gland obtained from eight cases at autopsy, who received no hormonal therapy and who revealed no significant changes in the pituitary and its target organs, was investigated in an attempt to identify human adenohypophyseal cells by comparing their secretory granules with those of experimental animals. Besides the follicular cell, five different granulated cell types were distinguished The Type 1 cell contained abundant, dense secretory granules (350-500 mmu across). The Type II cell was characterized by dense granules, which were the largest in size (500-700 mmu across) and the most irregular in shape. Granules of the Type III cell were less characteristic (200-300 mmu across). The Type IV cell contained dense granules, which were the smallest in size (100-150 mmu across) and were characteristically arranged along the plasma membrane. The Type V cell was characterized by the presence of small, haloed granules (100-200 mmu across). The cells of these five types could presumably be the somatotroph, lactotroph, gonadotroph, thyrotroph and corcitotroph, respectively."} {"id": "PMID:1274581", "title": "Enzyme histochemical observations of diffuse pulmonary fibrosis of rats experimentally induced by ionizing irradiation.", "content": "The right lungs of Sprague-Dauley rats were irradiated with single doses of 1000 r, 2000 r or 3000 r to induce radiation pneumonitis and diffuse fibrosis, and the alkaline and acid phosphatase (A1-Pase, Ac-Pase) activities of the lungs were observed histochemically. Only the lungs irradiated with 3000 r steadily exhibited sequential changes leading to radiation pneumonitis and subsequent diffuse fibrosis, whereas the lungs irradiated with 2000 r developed only some degree of radiation pneumonitis. Alveolar capillary endothelia in the lesion of pulmonary fibrosis exhibited an intense activity of A1-Pase, while the endothelia in all the other experimental conditions did not show this activity. Alveolar macrophages increased their sizes and the activity of Ac-Pase after the irradiation. In the later stages, large foamy macrophages with thin diffuse deposits of the reaction products became predominant. These macrophages never exhibited A1-Pase activity. Type II alveolar epithelial cells showed an intense A1-Pase activity on their microvilli, and their Ac-Pase activity was negligible in non-irradiated lungs. Bizarre cells, appearing at the stage of radiation pneumonitis, showed an intense A1-Pase activity on their cell membranes and a weak and diffuse Ac-Pase activity in their cytoplasms. Septal cells achieved the A1-Pase activity 3 or 4 weeks after the irradiation when mast cells were not yet seen in the alveolar septa.", "contents": "Enzyme histochemical observations of diffuse pulmonary fibrosis of rats experimentally induced by ionizing irradiation. The right lungs of Sprague-Dauley rats were irradiated with single doses of 1000 r, 2000 r or 3000 r to induce radiation pneumonitis and diffuse fibrosis, and the alkaline and acid phosphatase (A1-Pase, Ac-Pase) activities of the lungs were observed histochemically. Only the lungs irradiated with 3000 r steadily exhibited sequential changes leading to radiation pneumonitis and subsequent diffuse fibrosis, whereas the lungs irradiated with 2000 r developed only some degree of radiation pneumonitis. Alveolar capillary endothelia in the lesion of pulmonary fibrosis exhibited an intense activity of A1-Pase, while the endothelia in all the other experimental conditions did not show this activity. Alveolar macrophages increased their sizes and the activity of Ac-Pase after the irradiation. In the later stages, large foamy macrophages with thin diffuse deposits of the reaction products became predominant. These macrophages never exhibited A1-Pase activity. Type II alveolar epithelial cells showed an intense A1-Pase activity on their microvilli, and their Ac-Pase activity was negligible in non-irradiated lungs. Bizarre cells, appearing at the stage of radiation pneumonitis, showed an intense A1-Pase activity on their cell membranes and a weak and diffuse Ac-Pase activity in their cytoplasms. Septal cells achieved the A1-Pase activity 3 or 4 weeks after the irradiation when mast cells were not yet seen in the alveolar septa."} {"id": "PMID:1274582", "title": "Two autopsy cases of primary adenoacanthoma of the stomach.", "content": "The incidence of primary adenoacanthoma of the stomach is extremely low. In the Sasebo City Hospital, there were only two autopsy cases of adenoacanthoma among 46 cases of gastric cancer during the past four years. The first case was a 45-year-old female with metachronous triple cancers; adenoacanthoma of the stomach, squamous cell carcinoma of the uterus and squamous cell carcinoma of the tongue. Histological examination showed muconodular adenoacarcinoma of the stomach at the time of first operation and adenocanthoma at the time of autopsy. These two cases suggest that adenoacanthomas of the stomach may originate from squamous metaplasia or squamous differentiation of a preexisting glandular carcinoma.", "contents": "Two autopsy cases of primary adenoacanthoma of the stomach. The incidence of primary adenoacanthoma of the stomach is extremely low. In the Sasebo City Hospital, there were only two autopsy cases of adenoacanthoma among 46 cases of gastric cancer during the past four years. The first case was a 45-year-old female with metachronous triple cancers; adenoacanthoma of the stomach, squamous cell carcinoma of the uterus and squamous cell carcinoma of the tongue. Histological examination showed muconodular adenoacarcinoma of the stomach at the time of first operation and adenocanthoma at the time of autopsy. These two cases suggest that adenoacanthomas of the stomach may originate from squamous metaplasia or squamous differentiation of a preexisting glandular carcinoma."} {"id": "PMID:1274583", "title": "Mesenchymal hamartoma of the liver--an autopsy case with serial sections and some comments on its pathogenesis.", "content": "An autopsy case of mesenchymal hamartoma of the liver was reported and from the macroscopical observation and serial sections of the tumor the following findings were found: (1) macroscopically the tumor is supplied by only one large triad, (2) in the tumor hepatic lobular structure is fundamentally preserved and prolifereated bile ducts with surrounding fibrosis and many bile thrombi are mainly elongated and dilated Hering's canals, (3) the cysts connect with dilated interlobular bile ducts, (4) there are two portions, where connection of bile ducts is incomplete, that is, from Hering's canals to interlobular bile ducts and from interlobular ducts to large ducts in the large triad of (1), (5) almost all portal veins in the large triad of (2) are stenosed or obliterated by loose intimal fibrosis. From these findings it is considered that intrahepatic bile duct obstruction resulting in regional biliary cirrhosis is the fundamental process of this disease, and in addition the role of hemodynamic disturbance was discussed.", "contents": "Mesenchymal hamartoma of the liver--an autopsy case with serial sections and some comments on its pathogenesis. An autopsy case of mesenchymal hamartoma of the liver was reported and from the macroscopical observation and serial sections of the tumor the following findings were found: (1) macroscopically the tumor is supplied by only one large triad, (2) in the tumor hepatic lobular structure is fundamentally preserved and prolifereated bile ducts with surrounding fibrosis and many bile thrombi are mainly elongated and dilated Hering's canals, (3) the cysts connect with dilated interlobular bile ducts, (4) there are two portions, where connection of bile ducts is incomplete, that is, from Hering's canals to interlobular bile ducts and from interlobular ducts to large ducts in the large triad of (1), (5) almost all portal veins in the large triad of (2) are stenosed or obliterated by loose intimal fibrosis. From these findings it is considered that intrahepatic bile duct obstruction resulting in regional biliary cirrhosis is the fundamental process of this disease, and in addition the role of hemodynamic disturbance was discussed."} {"id": "PMID:1274584", "title": "Membranous glomerulonephritis associated with active liver cirrhosis both involved by HBs antigen.", "content": "This is a case report of a 35-year-old female who showed a relatively short clinical course of severe liver cirrhosis and proteinuria. On light microscopical studies of autopsy material, besides active postnecrotic type liver cirrhosis, typical membranous glomerulonephritis was found. Immunofluorescent study disclosed not only clustered HBsAg (hepatitis type B surface antigen) in occasional hepatic cells but also beaded granular type deposition of HBsAg, IgG, IgM, IgA and complement C3 along renal glomerular basement membrane (GBM). Electron microscopical study disclosed multiple particulated material in occasional inclusion bodies of hepatic cells and in subepithelial and subendothelial dense deposits along the GBM. Enzymatic immunoelectron microscopical study confirmed these particles especially along the GBM being HBsAg themselves. It was concluded that HBsAg-Ab (antibody) complex was the pathogenetic factor responsible for the glomerular change of this particular case. Although HBsAg and Ab were examined to be negative in serum throughout the patient's clinical course, the possibility of the presence of circulating HBsAg-Ab complex in serum was discussed.", "contents": "Membranous glomerulonephritis associated with active liver cirrhosis both involved by HBs antigen. This is a case report of a 35-year-old female who showed a relatively short clinical course of severe liver cirrhosis and proteinuria. On light microscopical studies of autopsy material, besides active postnecrotic type liver cirrhosis, typical membranous glomerulonephritis was found. Immunofluorescent study disclosed not only clustered HBsAg (hepatitis type B surface antigen) in occasional hepatic cells but also beaded granular type deposition of HBsAg, IgG, IgM, IgA and complement C3 along renal glomerular basement membrane (GBM). Electron microscopical study disclosed multiple particulated material in occasional inclusion bodies of hepatic cells and in subepithelial and subendothelial dense deposits along the GBM. Enzymatic immunoelectron microscopical study confirmed these particles especially along the GBM being HBsAg themselves. It was concluded that HBsAg-Ab (antibody) complex was the pathogenetic factor responsible for the glomerular change of this particular case. Although HBsAg and Ab were examined to be negative in serum throughout the patient's clinical course, the possibility of the presence of circulating HBsAg-Ab complex in serum was discussed."} {"id": "PMID:1274585", "title": "Myositis ossificans progressiva with parathyroid hyperplasia and polycystic ovary.", "content": "A report was made on an autopsy case of myositis ossificans progressiva in a girl who died at the age of 8 year and 11 months. The first symptom appeared as right wryneck ten days after birth. Parathyroid hyperplasia and polycystic ovary with high level of serum parathyroid hormone, FSH and LH were confirmed at autopsy. Parathyroid hyperactivity might be a secondary response to the continuous stimulation by increased peripheral consumption of calcium ions due to relentlessly progressive ossification in fibrous connective tissue.", "contents": "Myositis ossificans progressiva with parathyroid hyperplasia and polycystic ovary. A report was made on an autopsy case of myositis ossificans progressiva in a girl who died at the age of 8 year and 11 months. The first symptom appeared as right wryneck ten days after birth. Parathyroid hyperplasia and polycystic ovary with high level of serum parathyroid hormone, FSH and LH were confirmed at autopsy. Parathyroid hyperactivity might be a secondary response to the continuous stimulation by increased peripheral consumption of calcium ions due to relentlessly progressive ossification in fibrous connective tissue."} {"id": "PMID:1274586", "title": "Congenital brain and facial anomalies in the D1 trisomy syndrome--report of a case and a review of literature--.", "content": "On 58 cases of D1 trisomy, which were classified as those with seven separate D chromosomes, including the one in this report, congenital brain and facial anomalies were reviewed and discussed. Congenital brain defects in this syndrome might be classified into three groups: (I) grossly normal brain, (II) absence of olfactory bulbi and tracts, but normally-separated cerebral hemisphere, and (III) completely or incompletely uncleaved hemispheres with absence of olfactory bulbi and tracts. 25.9% of the cases were found in group I, 56.9% in group II, and 17.2% in group III, respectively. Although facial anomalies predicted the brain defects in group III, malformations of the face were not concerned with the brain defects in group I and II. There were no cases with both, normal brain and face.", "contents": "Congenital brain and facial anomalies in the D1 trisomy syndrome--report of a case and a review of literature--. On 58 cases of D1 trisomy, which were classified as those with seven separate D chromosomes, including the one in this report, congenital brain and facial anomalies were reviewed and discussed. Congenital brain defects in this syndrome might be classified into three groups: (I) grossly normal brain, (II) absence of olfactory bulbi and tracts, but normally-separated cerebral hemisphere, and (III) completely or incompletely uncleaved hemispheres with absence of olfactory bulbi and tracts. 25.9% of the cases were found in group I, 56.9% in group II, and 17.2% in group III, respectively. Although facial anomalies predicted the brain defects in group III, malformations of the face were not concerned with the brain defects in group I and II. There were no cases with both, normal brain and face."} {"id": "PMID:1274587", "title": "Increase in the amount of nuclear RNA in liver of ascites tumour-bearing mice.", "content": "The effect of tumour growth on the liver of the host was studied in the Ehrlich ascites tumour system. During the experimental period there was no infiltration of tumour cells in the liver, and the increase in the proliferation rate of Kupffer cells and parenchymal cells was only small. An increasing stability of the liver cell nuclei towards disruption during the isolation procedure was found to accompany the ascites tumour growth. In parallel, there was an increase in the amount of nuclear RNA and in the cellular speridine concentration. The major cause of these changes is probably an increasing demand on the liver by the growing tumour, illustrated by the fact that an amount of protein exceeding that of the whole liver accumulates in the ascites fluid during tumour growth. A hypothesis according to which the cellular accumulation of spermidine may be involved in the stabilization of cell nuclei and in the accumulation of nuclear RNA is advanced.", "contents": "Increase in the amount of nuclear RNA in liver of ascites tumour-bearing mice. The effect of tumour growth on the liver of the host was studied in the Ehrlich ascites tumour system. During the experimental period there was no infiltration of tumour cells in the liver, and the increase in the proliferation rate of Kupffer cells and parenchymal cells was only small. An increasing stability of the liver cell nuclei towards disruption during the isolation procedure was found to accompany the ascites tumour growth. In parallel, there was an increase in the amount of nuclear RNA and in the cellular speridine concentration. The major cause of these changes is probably an increasing demand on the liver by the growing tumour, illustrated by the fact that an amount of protein exceeding that of the whole liver accumulates in the ascites fluid during tumour growth. A hypothesis according to which the cellular accumulation of spermidine may be involved in the stabilization of cell nuclei and in the accumulation of nuclear RNA is advanced."} {"id": "PMID:1274588", "title": "The role of thymus for the development and prognosis of hypertension and hypertensive vascular disease in mice following renal infarction.", "content": "Partial infarction of one kidney and contralateral nephrectomy was followed by a rapid and significant increase in blood pressure both in haired mice with a normal thymus function and in nude mice with genetical aplasia of the thymus. The level of blood pressure and the prognosis were not influenced by the presence of thymus within the first 3 months after partial infarction of the kidney; but a significantly more pronounced increase in blood pressure after 4 months was observed in a small group of haired mice than in a similarly treated small group of nude mice. A marked degree of round cell infiltration around intrarenal arteries was only found in the haired mice, commencing 2 months after partial infarction of the kidney. Degenerative changes were observed in the kidneys of the haired mice 2-4 months after infarction. Very few of these lesions were found in the nude mice. Atempts to transfer the hypertension by means of viable lymph node cells from hypertensive donors to normotensive syngeneic recipients failed. The results support the assumption that high intravascular pressure induces thymus-dependent immune reactions against substances in teh vascular walls which, in turn, may have a prognostic significane; the results give no support for the assumption that the earlier phase of the hypertension which follows partial infarction of the kidney and contralateral nephrectomy is thymus-dependent.", "contents": "The role of thymus for the development and prognosis of hypertension and hypertensive vascular disease in mice following renal infarction. Partial infarction of one kidney and contralateral nephrectomy was followed by a rapid and significant increase in blood pressure both in haired mice with a normal thymus function and in nude mice with genetical aplasia of the thymus. The level of blood pressure and the prognosis were not influenced by the presence of thymus within the first 3 months after partial infarction of the kidney; but a significantly more pronounced increase in blood pressure after 4 months was observed in a small group of haired mice than in a similarly treated small group of nude mice. A marked degree of round cell infiltration around intrarenal arteries was only found in the haired mice, commencing 2 months after partial infarction of the kidney. Degenerative changes were observed in the kidneys of the haired mice 2-4 months after infarction. Very few of these lesions were found in the nude mice. Atempts to transfer the hypertension by means of viable lymph node cells from hypertensive donors to normotensive syngeneic recipients failed. The results support the assumption that high intravascular pressure induces thymus-dependent immune reactions against substances in teh vascular walls which, in turn, may have a prognostic significane; the results give no support for the assumption that the earlier phase of the hypertension which follows partial infarction of the kidney and contralateral nephrectomy is thymus-dependent."} {"id": "PMID:1274589", "title": "Cronic non-rheumatic valvular heart disease. An autopsy study.", "content": "The frequency of chronic non-rheumatic valvular heart disease in Iceland was investigated via autoposies performed from November 1965 through December 1974. During this period, about 12.400 Icelanders died at the age of 16 years and older and 28.8 per cent of these were included in the study. At autopsy, males outnumbered females by 2:1. The frequency of calcific aortic stenosis was found to be 3.63 per cent and the prevalence was calculated to be 3.17 per cent among males and 4.50 per cent among females. Calcific aortic stenosis in tricuspid valves was more frequent in females and calcific aortic stenosis in bicuspid valves was more frequent in males. Among the hearts with calcific aortic stenosis, 70.8 per cent were found to have normally tricuspid valves, 25.4 per cent bicuspid valves and 3.8 per cent tricuspid valves with an unicommissural fusion. In 0.59 per cent of the hearts the aortic valve was either bicuspid or had an uncommissural fusion without the features of calcific stenosis. However, a functional stenosis was suggested by the increased weight of most of these hearts. The frequency of bicuspid aortic valves was 1.2 per cent with a prevalence in males of 1.54 per cent and in females 0.50 per cent. A calcified mitral annulus was found in 1.98 per cent of the hearts and in most, it was either associated with calcific aortic stenosis in a tricuspid valve, or it was a single valvular disease. Rheumatic valvular disease was found in 1.08 per cent of the heart examined.", "contents": "Cronic non-rheumatic valvular heart disease. An autopsy study. The frequency of chronic non-rheumatic valvular heart disease in Iceland was investigated via autoposies performed from November 1965 through December 1974. During this period, about 12.400 Icelanders died at the age of 16 years and older and 28.8 per cent of these were included in the study. At autopsy, males outnumbered females by 2:1. The frequency of calcific aortic stenosis was found to be 3.63 per cent and the prevalence was calculated to be 3.17 per cent among males and 4.50 per cent among females. Calcific aortic stenosis in tricuspid valves was more frequent in females and calcific aortic stenosis in bicuspid valves was more frequent in males. Among the hearts with calcific aortic stenosis, 70.8 per cent were found to have normally tricuspid valves, 25.4 per cent bicuspid valves and 3.8 per cent tricuspid valves with an unicommissural fusion. In 0.59 per cent of the hearts the aortic valve was either bicuspid or had an uncommissural fusion without the features of calcific stenosis. However, a functional stenosis was suggested by the increased weight of most of these hearts. The frequency of bicuspid aortic valves was 1.2 per cent with a prevalence in males of 1.54 per cent and in females 0.50 per cent. A calcified mitral annulus was found in 1.98 per cent of the hearts and in most, it was either associated with calcific aortic stenosis in a tricuspid valve, or it was a single valvular disease. Rheumatic valvular disease was found in 1.08 per cent of the heart examined."} {"id": "PMID:1274590", "title": "Liver biopsies from psoriatics related to methotrexate therapy. 1. Findings in 123 consecutive non-methotrexate treated patients.", "content": "A prospective study was started in 1969 to describe morphological features of liver biopsies from patients with severe psoriasis. Among 123 patients evaluated for possible MTX therapy, liver biopsies disclosed pathological histology (maninly fatty change and/or non-specific reactive hepatitis) in 51 per cent. The incidence of pathological liver histology did not statistically correlate with psoriasis parameters such as duration and extent. However, statistically significant correlations (p less than 0.0001) were found between the frequency of pathological liver histology and other factors such as age, obesity, and daily alcholic intake. Comparison of liver histology with SGOT value at the time of liver biopsy showed that while the diagnostic specificy of this test high (1.00), the diagnostic was low (0.17). Normal values of SGOT should not be relied upon to indicate all types of liver pathology. A \"risk index\" indicating the probability of pathological liver histology was developed. It is calculated as follows: two times the height (cm) minus weight (kg) minus age (years) minus 50 (in case of daily alcoholic intake) minus 50 (in case of elevated SGOT). To elucidate liver histology and particularly to rule out fibrosis and cirrhosis, a liver biopsy should be performed in every psoriatic patient with a low score in the risk index prior to beginning MTX therapy.", "contents": "Liver biopsies from psoriatics related to methotrexate therapy. 1. Findings in 123 consecutive non-methotrexate treated patients. A prospective study was started in 1969 to describe morphological features of liver biopsies from patients with severe psoriasis. Among 123 patients evaluated for possible MTX therapy, liver biopsies disclosed pathological histology (maninly fatty change and/or non-specific reactive hepatitis) in 51 per cent. The incidence of pathological liver histology did not statistically correlate with psoriasis parameters such as duration and extent. However, statistically significant correlations (p less than 0.0001) were found between the frequency of pathological liver histology and other factors such as age, obesity, and daily alcholic intake. Comparison of liver histology with SGOT value at the time of liver biopsy showed that while the diagnostic specificy of this test high (1.00), the diagnostic was low (0.17). Normal values of SGOT should not be relied upon to indicate all types of liver pathology. A \"risk index\" indicating the probability of pathological liver histology was developed. It is calculated as follows: two times the height (cm) minus weight (kg) minus age (years) minus 50 (in case of daily alcoholic intake) minus 50 (in case of elevated SGOT). To elucidate liver histology and particularly to rule out fibrosis and cirrhosis, a liver biopsy should be performed in every psoriatic patient with a low score in the risk index prior to beginning MTX therapy."} {"id": "PMID:1274591", "title": "Liver biopsies from psoriatics related to methotrexate therapy. 2. Findings before and after methotexate therapy in 88 patients. A blind study.", "content": "Eightyeight patients with severe, recalcitrant psoriasis had liver biopsies performed before and after Methotrexate (MTX) therapy. MTX was given for an average of 26 months as a single, weekly, oral dose of 25 mg maximum. The mean cumulative dose was 1733 mg (range 175-4590 mg). A statistically significant increase in the number of pathological post-MTX liver biopsies was found (p less than 0.0001). Of the 88 patients 6 developed cirrhosis and another 5 developed fibrosis, in all 12.5 per cent, during MTX therapy (95 per cent confidence limits for cirrhosis: 3-14 per cent). There was no statistically significant correlation between the number of pathological post-MTX liver biopsy findings in the 88 patients and the following variables one by one: cumulative dose of MTX, duration of MTX therapy and admitted alcoholic intake during MTX therapy. Cirrhosis and fibrosis did not develop statistically more frequently from pathological than normal pre-MTX liver histology (p = 0.062). The liver damage appeared to be due to a multifactorial interaction of straining factors on the liver during MTX therapy. A multifactorial index comprising: cumulative dose of MTX, admitted alcoholic intake during MTX therapy, age, obesity and, if available, pre-MTX liver histology gave an estimate of the probability of developing cirrhosis or fibrosis during treatment of psoriasis with weekly, oral doses of MTX. For use of MTX therapy in psoriasis the following precautions are suggested: MTX therapy should be used only in disabling cases; a pre-MTX liver biopsy and repeat liver biopsies at regular intervals of 1/2-1 year should be performed, alcohol should be prohibited and frequent inquiries should be made about the patient's alcoholic intake; and strong reliance should not be placed on the SGOT as an indicator of abnormal liver histology.", "contents": "Liver biopsies from psoriatics related to methotrexate therapy. 2. Findings before and after methotexate therapy in 88 patients. A blind study. Eightyeight patients with severe, recalcitrant psoriasis had liver biopsies performed before and after Methotrexate (MTX) therapy. MTX was given for an average of 26 months as a single, weekly, oral dose of 25 mg maximum. The mean cumulative dose was 1733 mg (range 175-4590 mg). A statistically significant increase in the number of pathological post-MTX liver biopsies was found (p less than 0.0001). Of the 88 patients 6 developed cirrhosis and another 5 developed fibrosis, in all 12.5 per cent, during MTX therapy (95 per cent confidence limits for cirrhosis: 3-14 per cent). There was no statistically significant correlation between the number of pathological post-MTX liver biopsy findings in the 88 patients and the following variables one by one: cumulative dose of MTX, duration of MTX therapy and admitted alcoholic intake during MTX therapy. Cirrhosis and fibrosis did not develop statistically more frequently from pathological than normal pre-MTX liver histology (p = 0.062). The liver damage appeared to be due to a multifactorial interaction of straining factors on the liver during MTX therapy. A multifactorial index comprising: cumulative dose of MTX, admitted alcoholic intake during MTX therapy, age, obesity and, if available, pre-MTX liver histology gave an estimate of the probability of developing cirrhosis or fibrosis during treatment of psoriasis with weekly, oral doses of MTX. For use of MTX therapy in psoriasis the following precautions are suggested: MTX therapy should be used only in disabling cases; a pre-MTX liver biopsy and repeat liver biopsies at regular intervals of 1/2-1 year should be performed, alcohol should be prohibited and frequent inquiries should be made about the patient's alcoholic intake; and strong reliance should not be placed on the SGOT as an indicator of abnormal liver histology."} {"id": "PMID:1274592", "title": "Bile canalicular alkaline phosphatase in necropsy specimens of the liver and its relation to disease.", "content": "The histochemical patterns of the alkaline phosphatase reaction in liver specimens obtained at 185 consecutive autopsies were studied for any correlation with clinical data and post mortem findings. Alkaline phosphatase activity of bile canaliculi was found in 71 per cent of the subjects with malignant tumours not involving the liver, and in 77 per cent of the subjects with malignant tumours involving the liver. The histochemical pattern did not differ with the type of tumour. Most subjects with rheumatoid arthritis as well as most of those with centrolobular hepatic necrosis due to heart incompensation also showed alkaline phosphatase activity in the bile canaliculi.", "contents": "Bile canalicular alkaline phosphatase in necropsy specimens of the liver and its relation to disease. The histochemical patterns of the alkaline phosphatase reaction in liver specimens obtained at 185 consecutive autopsies were studied for any correlation with clinical data and post mortem findings. Alkaline phosphatase activity of bile canaliculi was found in 71 per cent of the subjects with malignant tumours not involving the liver, and in 77 per cent of the subjects with malignant tumours involving the liver. The histochemical pattern did not differ with the type of tumour. Most subjects with rheumatoid arthritis as well as most of those with centrolobular hepatic necrosis due to heart incompensation also showed alkaline phosphatase activity in the bile canaliculi."} {"id": "PMID:1274593", "title": "Vast and apparently paradoxical continuous rise in plasma renin after removal of gently manipulated submaxillary glands in nephrectomized mice.", "content": "Gentle manipulation of the submaxillary glands of previously nephrectomized mice results in a vast increase in plasma renin concentration. The concentration reaches 1 to 7 G.U. renin/ml, which is 1,000-fold higher than normal plasma concentrations. The rise is much less pronounced if the glands are removed after the manipulation, confirming the site of the release. However, an apparent paradox is seen: the renin concentration continues to rise even after removal of submaxillary glands as well as kidneys, indicating that a bound a form of renin is also released. The bound renin can be in the form of exocytosed granules or (and) in the form of \"protein\", the renin of which is activated with time. In spite of the very high renin concentrations the blood pressure is normal or only moderately increased. This disproportion between plasma renin and blood pressure can be caused by a simultaneous release of submaxillary kallikrein and renin, which have conteracting effects on the blood pressure.", "contents": "Vast and apparently paradoxical continuous rise in plasma renin after removal of gently manipulated submaxillary glands in nephrectomized mice. Gentle manipulation of the submaxillary glands of previously nephrectomized mice results in a vast increase in plasma renin concentration. The concentration reaches 1 to 7 G.U. renin/ml, which is 1,000-fold higher than normal plasma concentrations. The rise is much less pronounced if the glands are removed after the manipulation, confirming the site of the release. However, an apparent paradox is seen: the renin concentration continues to rise even after removal of submaxillary glands as well as kidneys, indicating that a bound a form of renin is also released. The bound renin can be in the form of exocytosed granules or (and) in the form of \"protein\", the renin of which is activated with time. In spite of the very high renin concentrations the blood pressure is normal or only moderately increased. This disproportion between plasma renin and blood pressure can be caused by a simultaneous release of submaxillary kallikrein and renin, which have conteracting effects on the blood pressure."} {"id": "PMID:1274594", "title": "Enterotoxin, haemolysin and cytotoxic protein in Aeromonas hydrophila from human infections.", "content": "Three different toxins were detected in culture supernatants from 11 strains of Aeromonas hydrophila. The haemolysin and the cytotoxic factor(s) interferred in the three test systems for enterotoxin, but they could be neutralized by heating at 56 degrees C or by specific antihaemolysin.", "contents": "Enterotoxin, haemolysin and cytotoxic protein in Aeromonas hydrophila from human infections. Three different toxins were detected in culture supernatants from 11 strains of Aeromonas hydrophila. The haemolysin and the cytotoxic factor(s) interferred in the three test systems for enterotoxin, but they could be neutralized by heating at 56 degrees C or by specific antihaemolysin."} {"id": "PMID:1274595", "title": "The effect of acute rise in intracranial pressure on the sympathetic cardiac, vertebral and phrenic nerve activities.", "content": "A transient rise of intracranial pressure in cats under chloralose-urethane anaesthesia increased the activity of the sympathetic vertebral nerve, cardiac nerve and in the first phase phrenic nerve. If the vagus nerves were intact this rise in sympathetic activity was associated with bradycardia. These effects developed with a delay, as a rule after abatement of the transient intracranial pressure rise. The authors suggest that Cushing's reaction is caused by medullary ischaemia and development of local metabolic acidosis activating simultaneously the sympathetic and parasympathetic neurons in the medulla oblongata.", "contents": "The effect of acute rise in intracranial pressure on the sympathetic cardiac, vertebral and phrenic nerve activities. A transient rise of intracranial pressure in cats under chloralose-urethane anaesthesia increased the activity of the sympathetic vertebral nerve, cardiac nerve and in the first phase phrenic nerve. If the vagus nerves were intact this rise in sympathetic activity was associated with bradycardia. These effects developed with a delay, as a rule after abatement of the transient intracranial pressure rise. The authors suggest that Cushing's reaction is caused by medullary ischaemia and development of local metabolic acidosis activating simultaneously the sympathetic and parasympathetic neurons in the medulla oblongata."} {"id": "PMID:1274596", "title": "Lack of stimulating effect of hypertonic Nacl intravenous injection on the release of melanocyte-stimulating hormone from the hypothalamic end of the cut pituitary stalk.", "content": "After removal of the whole pituitary gland in the rat, intravenous injection of 5% NaCl solution (0.5% of body weight) had no effect on MSH release from the washed hypothalamic end of the cut pituitary stalk and the ventral surface of the median eminence.", "contents": "Lack of stimulating effect of hypertonic Nacl intravenous injection on the release of melanocyte-stimulating hormone from the hypothalamic end of the cut pituitary stalk. After removal of the whole pituitary gland in the rat, intravenous injection of 5% NaCl solution (0.5% of body weight) had no effect on MSH release from the washed hypothalamic end of the cut pituitary stalk and the ventral surface of the median eminence."} {"id": "PMID:1274598", "title": "A method of evoking fast baroreceptor responses for the measurement of the baroreflex latency.", "content": "A method for measurement of latency in the baroreflex is described. Standardised square pressure pulse was applied to the isolated carotid sinus and simultaneous recordings of the carotid sinus nerve or sympathetic fibers were performed. Relatively short time of the increase of the pressure makes possible more exact measurements of latency in the baroreflex than other known methods used for this purpose.", "contents": "A method of evoking fast baroreceptor responses for the measurement of the baroreflex latency. A method for measurement of latency in the baroreflex is described. Standardised square pressure pulse was applied to the isolated carotid sinus and simultaneous recordings of the carotid sinus nerve or sympathetic fibers were performed. Relatively short time of the increase of the pressure makes possible more exact measurements of latency in the baroreflex than other known methods used for this purpose."} {"id": "PMID:1274599", "title": "Effects of acetylcholine and other vasodilatory substances in the vascular bed of skeletal muscles during and after muscular contractions.", "content": "In dogs and cats perfusion pressure or femoral venous outflow and changes in the volume of the hind limb were measured. The influence of muscular contractions on the effects of acetylcholine, histamine, isoprenaline and papaverine in the vascular bed of the limb was investigated. It was found that after muscular excerise the effects of i. a. injection of acetylcholine into the isolated limb were markedly potentiated, whereas the effects of histamine and isoprenaline were diminished.", "contents": "Effects of acetylcholine and other vasodilatory substances in the vascular bed of skeletal muscles during and after muscular contractions. In dogs and cats perfusion pressure or femoral venous outflow and changes in the volume of the hind limb were measured. The influence of muscular contractions on the effects of acetylcholine, histamine, isoprenaline and papaverine in the vascular bed of the limb was investigated. It was found that after muscular excerise the effects of i. a. injection of acetylcholine into the isolated limb were markedly potentiated, whereas the effects of histamine and isoprenaline were diminished."} {"id": "PMID:1274600", "title": "Effect of propranolol on thyroxine-induced changes in body temperature and metabolism during exercise in dogs.", "content": "Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s.c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (Tre) during exercise as early as 5h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest Tre, blood FFA and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in Tre and blood LA concentrations during the next 30 min of exercise.", "contents": "Effect of propranolol on thyroxine-induced changes in body temperature and metabolism during exercise in dogs. Effects of thyroxine on temperature and metabolism during exercise were studied in dogs after beta-adrenergic blockade. Dogs performed 60 min treadmill exercise of moderate intensity 5 and 72 h following thyroxine injected s.c. in a single dose of 0.1 mg/kg b.w. Thyroxine increased significantly the lipolytic response to exercise as well as blood lactate (LA) concentrations and rectal temperature (Tre) during exercise as early as 5h following the hormone administration. The changes became more pronounced 72 h after the injection. At rest Tre, blood FFA and LA levels in the thyroxine-treated dogs did not differ from the control values, and blood glucose was slightly, but significantly higher. Propranolol given intravenously in a dose of 0.25 mg/kg at 30 min of the exercise performed 72 h following thyroxine injection abolished the plasma FFA rise, and inhibited to a certain extent increases in Tre and blood LA concentrations during the next 30 min of exercise."} {"id": "PMID:1274603", "title": "The effects of bradykinin on electrobiological phenomena in isolated right atrium of the rat.", "content": "Bradykinin induces or accelerates the already present electrobiological activity in isolated right atrium of rats. Acceleration of the electrobiological activity induced by bradykinin decreases with increase of initial activity. Bradykinin disturbs transiently the course of the repolarization period in action potential. It may be one of the mechanisms of arrhythmia development caused by bradykinin.", "contents": "The effects of bradykinin on electrobiological phenomena in isolated right atrium of the rat. Bradykinin induces or accelerates the already present electrobiological activity in isolated right atrium of rats. Acceleration of the electrobiological activity induced by bradykinin decreases with increase of initial activity. Bradykinin disturbs transiently the course of the repolarization period in action potential. It may be one of the mechanisms of arrhythmia development caused by bradykinin."} {"id": "PMID:1274601", "title": "Effect of physical training on the permeability of vascular bed to albumin labelled with T-1824.", "content": "Two-week physical training caused in dogs a rise in vascular permeability by 40--50% persisting for at least 24 hours after the last run. Simultaneously, the obtained results point out that physical training leads to increased production and flow of lymph and to increased turnover rate of substances between the intra- and extravascular spaces in the animals at rest.", "contents": "Effect of physical training on the permeability of vascular bed to albumin labelled with T-1824. Two-week physical training caused in dogs a rise in vascular permeability by 40--50% persisting for at least 24 hours after the last run. Simultaneously, the obtained results point out that physical training leads to increased production and flow of lymph and to increased turnover rate of substances between the intra- and extravascular spaces in the animals at rest."} {"id": "PMID:1274604", "title": "Experimental studies on osmotic mechanisms and vegetative regulations of intraocular hydrodynamics as well as the distribution of elecrolytes and amino-acids in refractive environments of the eye.", "content": "The studies were carried out on the influence of hyperosmolar loading with glycerol and hypoosmotic glucose, as well as on the effect of pharmacological stimulation of the adrenergic system after sympathetic decentralization of the eyes, and of the cholinergic stimulation, on intraocular hydrodynamics, and on the distribution of electrolytes and amino-acids in refractive environments. The results showed a dependence between the changes in blood osmolality and osmotic intraocular activity, and the secretion and flow of the aqueous humor, as well as the distribution of electrolytes and amino-acids. No specific, antagonistic influence of the adrenergic and cholinergic stimulation on the hydrodynamics and the distribution of electrolytes and amino-acids in refractive environments has been found. The opposite reactions to stimulation of adrenergic alpha or beta-receptors have been observed.", "contents": "Experimental studies on osmotic mechanisms and vegetative regulations of intraocular hydrodynamics as well as the distribution of elecrolytes and amino-acids in refractive environments of the eye. The studies were carried out on the influence of hyperosmolar loading with glycerol and hypoosmotic glucose, as well as on the effect of pharmacological stimulation of the adrenergic system after sympathetic decentralization of the eyes, and of the cholinergic stimulation, on intraocular hydrodynamics, and on the distribution of electrolytes and amino-acids in refractive environments. The results showed a dependence between the changes in blood osmolality and osmotic intraocular activity, and the secretion and flow of the aqueous humor, as well as the distribution of electrolytes and amino-acids. No specific, antagonistic influence of the adrenergic and cholinergic stimulation on the hydrodynamics and the distribution of electrolytes and amino-acids in refractive environments has been found. The opposite reactions to stimulation of adrenergic alpha or beta-receptors have been observed."} {"id": "PMID:1274602", "title": "The post-exercise glycogen recovery in tissues of trained rats.", "content": "The post-exercise glycogen recovery in myocardium, liver, diaphragm muscle and musculus biceps femoris was compared in untrained and trained rats. The glycogen level in myocardium of the trained rats was significantly higher than that in the untrained ones only immediately after the exercise-test and on the second day after the exercise. The liver glycogen levels on each of the examined post-exercise days were similar in both groups and did not differ from the control values. The post-exercise glycogen recovery in the diapraghm muscle of the untrained rats was also similar to that in the trained animals. In musculus bicpes femoris similar post-exercise supercompensation was found in both groups except on the second day when the glycogen level in the trained animals was significantly higher than that in the untrained ones. The results suggest that it is necessary to separate the effects of training from those of the last bout of exercise in the training program when the effect of training is examined.", "contents": "The post-exercise glycogen recovery in tissues of trained rats. The post-exercise glycogen recovery in myocardium, liver, diaphragm muscle and musculus biceps femoris was compared in untrained and trained rats. The glycogen level in myocardium of the trained rats was significantly higher than that in the untrained ones only immediately after the exercise-test and on the second day after the exercise. The liver glycogen levels on each of the examined post-exercise days were similar in both groups and did not differ from the control values. The post-exercise glycogen recovery in the diapraghm muscle of the untrained rats was also similar to that in the trained animals. In musculus bicpes femoris similar post-exercise supercompensation was found in both groups except on the second day when the glycogen level in the trained animals was significantly higher than that in the untrained ones. The results suggest that it is necessary to separate the effects of training from those of the last bout of exercise in the training program when the effect of training is examined."} {"id": "PMID:1274605", "title": "Neural control of breathing: a system analysis.", "content": "A model of the neural control of quiet breathing in an anaesthetised and tracheostomised laboratory animal is presented. The loop consisting of the brain generator with its respiratory \"master function\", the phrenic command, the aerodynamics of the lungs and the volume information carried by the vagus nerves is described in mathematical terms. Computer model experiments are presented and compared with corresponding physiological situations. The stability of the model is demonstrated.", "contents": "Neural control of breathing: a system analysis. A model of the neural control of quiet breathing in an anaesthetised and tracheostomised laboratory animal is presented. The loop consisting of the brain generator with its respiratory \"master function\", the phrenic command, the aerodynamics of the lungs and the volume information carried by the vagus nerves is described in mathematical terms. Computer model experiments are presented and compared with corresponding physiological situations. The stability of the model is demonstrated."} {"id": "PMID:1274606", "title": "A decreased hyperglycemic response to adrenaline after prolonged, exhausting exercise in dogs.", "content": "The aim of the investigations carried out on dogs was to elucidate possible causes of the decreased hyperglycemic response to adrenaline after exhausting exercise. The k-values of i.v. glucose tolerance tests were calculated and the dose-response relationship to infused adrenaline was analyzed under control, resting conditions, and after exhausting exercise. K-values (KG-exc.) were significantly higher (p less than 0.01) after exercise than in control experiments, whereas hyperglycemic responses to the applied doses of adrenaline: 0.25, 0.5, 1.0, 2.0 and 3.0 mug-kg-1min-1 were considerably lower. In both situations a linear relationship was found between the hyperglycemic response and the dose of adrenaline, although the slope of the regression line, expressing this relationship, was significantly lower after exercise than that under control conditions. It is suggested that the decreased hyperglycemic response to adrenaline after prolonged, exhausting exercise may be attributed to both the increased rate of glucose elimination from blood, and a decreased responsiveness of the liver to adrenaline.", "contents": "A decreased hyperglycemic response to adrenaline after prolonged, exhausting exercise in dogs. The aim of the investigations carried out on dogs was to elucidate possible causes of the decreased hyperglycemic response to adrenaline after exhausting exercise. The k-values of i.v. glucose tolerance tests were calculated and the dose-response relationship to infused adrenaline was analyzed under control, resting conditions, and after exhausting exercise. K-values (KG-exc.) were significantly higher (p less than 0.01) after exercise than in control experiments, whereas hyperglycemic responses to the applied doses of adrenaline: 0.25, 0.5, 1.0, 2.0 and 3.0 mug-kg-1min-1 were considerably lower. In both situations a linear relationship was found between the hyperglycemic response and the dose of adrenaline, although the slope of the regression line, expressing this relationship, was significantly lower after exercise than that under control conditions. It is suggested that the decreased hyperglycemic response to adrenaline after prolonged, exhausting exercise may be attributed to both the increased rate of glucose elimination from blood, and a decreased responsiveness of the liver to adrenaline."} {"id": "PMID:1274607", "title": "An influence of exercise of increasing intensity on aminotransferase activity and electrolyte level in red blood cells and blood serum in men with average and very high physical working capacity.", "content": "Healthy subjects with average and very high physical working capacity were submitted to two 6-min periods of work on a cycloergometer at the work loads 70 and 90 percent VO2max. Changes in the activity of Asp AT and Al AT as well as in the concentrations of NA, K and lactates in erythrocytes and serum were determined. In the subjects with average physical working capacity the serum concentrations of lactate and sodium, as well as the activity of Asp AT were much more increased than in the highly efficient subjects. In both groups similar changes of electrolyte concentrations in erythrocytes occured. The activity of Al AT was increased only in the group of subjects with high physical working capacity after the first period of work and showed a tendency to return to the resting values after the second period.", "contents": "An influence of exercise of increasing intensity on aminotransferase activity and electrolyte level in red blood cells and blood serum in men with average and very high physical working capacity. Healthy subjects with average and very high physical working capacity were submitted to two 6-min periods of work on a cycloergometer at the work loads 70 and 90 percent VO2max. Changes in the activity of Asp AT and Al AT as well as in the concentrations of NA, K and lactates in erythrocytes and serum were determined. In the subjects with average physical working capacity the serum concentrations of lactate and sodium, as well as the activity of Asp AT were much more increased than in the highly efficient subjects. In both groups similar changes of electrolyte concentrations in erythrocytes occured. The activity of Al AT was increased only in the group of subjects with high physical working capacity after the first period of work and showed a tendency to return to the resting values after the second period."} {"id": "PMID:1274609", "title": "The effect of poisoning with Dithane M-45 on oxygen uptake and energy balance in adult rats.", "content": "Adult white rats were kept on natural diet containing various doses of Dithane M-45 (Mn and Zn ethylene-bisdithiocarbamate). Oxygen uptake (VO2), metabolic rate and energy balance were determined at intervals of several days. Oxygen uptake and metabolic rate were not significantly changed in animals receiving Dithane M-45 in concentrations of 5 and 50 ppm but they were significantly decreased in the animals kept on the diet containing the preparation in concentrations of 500, 2000 and 5000 ppm. The authors conclude that changes in body weight of animals after poisoning with Dithane M-45 are due, both to reduced supply and requirements for energy.", "contents": "The effect of poisoning with Dithane M-45 on oxygen uptake and energy balance in adult rats. Adult white rats were kept on natural diet containing various doses of Dithane M-45 (Mn and Zn ethylene-bisdithiocarbamate). Oxygen uptake (VO2), metabolic rate and energy balance were determined at intervals of several days. Oxygen uptake and metabolic rate were not significantly changed in animals receiving Dithane M-45 in concentrations of 5 and 50 ppm but they were significantly decreased in the animals kept on the diet containing the preparation in concentrations of 500, 2000 and 5000 ppm. The authors conclude that changes in body weight of animals after poisoning with Dithane M-45 are due, both to reduced supply and requirements for energy."} {"id": "PMID:1274608", "title": "Diurnal and seasonal variations of glycogen content in the rat brain.", "content": "The effect of seasonal and diurnal variations on glycogen content in the brain was investigated in 3-month old Wistar rats. In the first experimental series, the glycogen content in the brain was determined every 2-months, throughout a whole year. In each experiment, the material was taken at the same time of a day. The results indicated that the brain glycogen content did not change significantly, during the periods of a year examined. In the second series of experiments, the glycogen content in the rat brain was assayed every 3 hours, during a 24-hour-period. A low content of glycogen in the rat brain was found during the night, with a pronounced decrease of this value between 9.00 p.m. and midnight. A possible relationship between the diurnal changes in the brain glycogen content and catecholamine metabolism in the central nervous system is discussed.", "contents": "Diurnal and seasonal variations of glycogen content in the rat brain. The effect of seasonal and diurnal variations on glycogen content in the brain was investigated in 3-month old Wistar rats. In the first experimental series, the glycogen content in the brain was determined every 2-months, throughout a whole year. In each experiment, the material was taken at the same time of a day. The results indicated that the brain glycogen content did not change significantly, during the periods of a year examined. In the second series of experiments, the glycogen content in the rat brain was assayed every 3 hours, during a 24-hour-period. A low content of glycogen in the rat brain was found during the night, with a pronounced decrease of this value between 9.00 p.m. and midnight. A possible relationship between the diurnal changes in the brain glycogen content and catecholamine metabolism in the central nervous system is discussed."} {"id": "PMID:1274613", "title": "Studies of cerebral osmoreceptors in anesthetized dogs: the effect of intravenous and intracarotid infusion of hyper-osmolar sodium chloride solutions during sustained water diuresis.", "content": "The function of the suggested hypothalamic osmoreceptors was investigated in dogs during light chloralose anesthesia. The dogs were subjected to an i.v. load of 40 ml/kg b.w.t. of a hypo-osmolar solution of sodium chloride and glucose. This degree of hydration was kept constantly by a specially constructed servo system based on the weight of the animal. During water diuresis the renal free water clearance remained essentially constant for several hours (mean about 0.2 ml/kg b.w.t. min). Renal sodium excretion was low (mean 0.82 mumol/kg b.w.t. min) and decreased continuously throughout the experimental period. I.v. infusion of hyperosmolar sodium chloride solution (1.33 mmol/kg b.w.t. in 30 min) was followed by prolonged parallel increases in free water clearance and sodium excretion, without any detectable change in the excretion of osmoles and potassium. The renal response to bilateral infusion of hyper-osmolar NaCl (1.33 mmol/kg b.w.t. in 30 min) into the common carotid arteries was identical to the response to i.v. infusion. The estimated increase in the osmolality of the carotid blood was 2.2%. In seven out of eight experiments intracarotid infusion of NaCl (1.33 mmol/kg b.w.t. in 8 min) did not elicit any reduction in free water clearance. On the contrary, an increase was found similar to that obtained after i.v. infusion. The estimated increase in the osmolality of the carotid blood was 8.4%. The present results question the validity of the currently held view that hypothalamic osmoreceptors play an important role in the control of the osmolality of plasma.", "contents": "Studies of cerebral osmoreceptors in anesthetized dogs: the effect of intravenous and intracarotid infusion of hyper-osmolar sodium chloride solutions during sustained water diuresis. The function of the suggested hypothalamic osmoreceptors was investigated in dogs during light chloralose anesthesia. The dogs were subjected to an i.v. load of 40 ml/kg b.w.t. of a hypo-osmolar solution of sodium chloride and glucose. This degree of hydration was kept constantly by a specially constructed servo system based on the weight of the animal. During water diuresis the renal free water clearance remained essentially constant for several hours (mean about 0.2 ml/kg b.w.t. min). Renal sodium excretion was low (mean 0.82 mumol/kg b.w.t. min) and decreased continuously throughout the experimental period. I.v. infusion of hyperosmolar sodium chloride solution (1.33 mmol/kg b.w.t. in 30 min) was followed by prolonged parallel increases in free water clearance and sodium excretion, without any detectable change in the excretion of osmoles and potassium. The renal response to bilateral infusion of hyper-osmolar NaCl (1.33 mmol/kg b.w.t. in 30 min) into the common carotid arteries was identical to the response to i.v. infusion. The estimated increase in the osmolality of the carotid blood was 2.2%. In seven out of eight experiments intracarotid infusion of NaCl (1.33 mmol/kg b.w.t. in 8 min) did not elicit any reduction in free water clearance. On the contrary, an increase was found similar to that obtained after i.v. infusion. The estimated increase in the osmolality of the carotid blood was 8.4%. The present results question the validity of the currently held view that hypothalamic osmoreceptors play an important role in the control of the osmolality of plasma."} {"id": "PMID:1274610", "title": "Normal values of blood morphotic elements, haematocrit and bone marrow cell pattern in adult Wistar rats.", "content": "Since normal values of blood morphotic elements, haematocrit, and bone marrow cell pattern reported for adult Wistar rats by various authors differ investigations were carried out on a relatively large group of animals. The results were compared with the normal values obtained by other authors.", "contents": "Normal values of blood morphotic elements, haematocrit and bone marrow cell pattern in adult Wistar rats. Since normal values of blood morphotic elements, haematocrit, and bone marrow cell pattern reported for adult Wistar rats by various authors differ investigations were carried out on a relatively large group of animals. The results were compared with the normal values obtained by other authors."} {"id": "PMID:1274614", "title": "Effects on renal water and sodium excretion of infusions of either iso-osmolar saline or a hypo-osmolar solution of non-electrolytes.", "content": "The effects of iso-osmolar and hypo-osmolar volume expansion on renal water and sodium excretion were studied in dogs during light chloralose anesthesia. Saline or a hypo-osmolar of glucose and urea was given i.v. (20 ml/kg b.w.t. in 60 min). From the start of this infusion the combined weight of the hydration infusate and the dog was maintained constant by a servo system, which controlled the rate of infusion of a hypo-osmolar solution. Consequently the degree of hydration increased linearly during the infusion period after which it remained constant throughout the experiment. No increase in free water clearance was seen after iso-osmolar volume expansion. The rate of excretion of sodium increased considerably. Hypo-osmolar volume expansion provoked a water diuresis during which the rate of excretion of sodium fell to less than 0.1 mumol/kg b.w.t. min. It is concluded that under the present circumstances infusion of iso-osmolar saline is not associated with a decrease in the rate of secretion of vasopressin.", "contents": "Effects on renal water and sodium excretion of infusions of either iso-osmolar saline or a hypo-osmolar solution of non-electrolytes. The effects of iso-osmolar and hypo-osmolar volume expansion on renal water and sodium excretion were studied in dogs during light chloralose anesthesia. Saline or a hypo-osmolar of glucose and urea was given i.v. (20 ml/kg b.w.t. in 60 min). From the start of this infusion the combined weight of the hydration infusate and the dog was maintained constant by a servo system, which controlled the rate of infusion of a hypo-osmolar solution. Consequently the degree of hydration increased linearly during the infusion period after which it remained constant throughout the experiment. No increase in free water clearance was seen after iso-osmolar volume expansion. The rate of excretion of sodium increased considerably. Hypo-osmolar volume expansion provoked a water diuresis during which the rate of excretion of sodium fell to less than 0.1 mumol/kg b.w.t. min. It is concluded that under the present circumstances infusion of iso-osmolar saline is not associated with a decrease in the rate of secretion of vasopressin."} {"id": "PMID:1274611", "title": "Distribution and retention of indium113m in the organism of pregnant rats.", "content": "The distribution and retention of intravenously administered indium (113mInCl3) were determined in pregnant female rats. The highest accumulation of indium was found in the placenta during the last period of pregnancy. Five hours after administration the retention of indium in the placenta was about 38% of the administered dose. In the fetuses of these females the amount of radioactive indium did not exceed 1% of the injected dose. In the last period of pregnancy the placenta is the critical organ for intravenously administered administered indium (InCl3).", "contents": "Distribution and retention of indium113m in the organism of pregnant rats. The distribution and retention of intravenously administered indium (113mInCl3) were determined in pregnant female rats. The highest accumulation of indium was found in the placenta during the last period of pregnancy. Five hours after administration the retention of indium in the placenta was about 38% of the administered dose. In the fetuses of these females the amount of radioactive indium did not exceed 1% of the injected dose. In the last period of pregnancy the placenta is the critical organ for intravenously administered administered indium (InCl3)."} {"id": "PMID:1274615", "title": "Effects of lesions in the parabrachial nucleus on the mechanisms for central and reflex termination of inspiration in the cat.", "content": "The effects of PCO2 and body temperature on the time course and peak amplitude of the central inspiratory activity (CIA) and the inspiratory \"off-switch\" threshold was studied in apneustic and non-apneustic cats. Apneusis resulted from lesions of the inspiratory inhibiting structures of the medial parabrachial nucleus (NPBM) and by interrupting vagal volume feedback. The cats were paralyzed and ventilated either proportionally to their phrenic output or at predetermined rate and volume. The dependence of the rate of rise and maximal amplitude of phrenic activity on PCO2 and body temperature were comparable in apneustic and non-lesioned animals. The Hering-Breuer volume threshold for inspiratory termination was increased following the rostral pontine lesions. Both hyperthermia and hypercapnia caused augmentation of the absolute rate of rise of inspiratory activity but hypercapnia, in contrast to hyperthermia, caused virtually no change in the fractional increment per unit time. With hypercapnia the inspiratory \"off-switch\" threshold was raised in the apneustic animals in intact ones, whereas hyperthermia did not seem to influence this threshold. In apneustic conditions expiratory duration remained constant, independent of the large variations in the inspiratory durations. Our results suggest that the NPBM merely provides an excitatory, threshold-lowering input to the inspiratory \"off-switch\" mechanism.", "contents": "Effects of lesions in the parabrachial nucleus on the mechanisms for central and reflex termination of inspiration in the cat. The effects of PCO2 and body temperature on the time course and peak amplitude of the central inspiratory activity (CIA) and the inspiratory \"off-switch\" threshold was studied in apneustic and non-apneustic cats. Apneusis resulted from lesions of the inspiratory inhibiting structures of the medial parabrachial nucleus (NPBM) and by interrupting vagal volume feedback. The cats were paralyzed and ventilated either proportionally to their phrenic output or at predetermined rate and volume. The dependence of the rate of rise and maximal amplitude of phrenic activity on PCO2 and body temperature were comparable in apneustic and non-lesioned animals. The Hering-Breuer volume threshold for inspiratory termination was increased following the rostral pontine lesions. Both hyperthermia and hypercapnia caused augmentation of the absolute rate of rise of inspiratory activity but hypercapnia, in contrast to hyperthermia, caused virtually no change in the fractional increment per unit time. With hypercapnia the inspiratory \"off-switch\" threshold was raised in the apneustic animals in intact ones, whereas hyperthermia did not seem to influence this threshold. In apneustic conditions expiratory duration remained constant, independent of the large variations in the inspiratory durations. Our results suggest that the NPBM merely provides an excitatory, threshold-lowering input to the inspiratory \"off-switch\" mechanism."} {"id": "PMID:1274612", "title": "The effect of restriction of physical activity on adaptation to prolonged exercise in dogs.", "content": "Eight-week restriction of physical activity markedly reduced the capacity for prolonged running. The rate of exercise-induced Tre increases was also significantly higher in comparison with control experiments. At the point of exhaustion blood glucose concentration and muscle glycogen content were similar in the control and cage-confined animals, however the rate of decrease in blood glucose level and muscle glycogen depletion during exercise were higher in the cage-confined dogs than in the controls.", "contents": "The effect of restriction of physical activity on adaptation to prolonged exercise in dogs. Eight-week restriction of physical activity markedly reduced the capacity for prolonged running. The rate of exercise-induced Tre increases was also significantly higher in comparison with control experiments. At the point of exhaustion blood glucose concentration and muscle glycogen content were similar in the control and cage-confined animals, however the rate of decrease in blood glucose level and muscle glycogen depletion during exercise were higher in the cage-confined dogs than in the controls."} {"id": "PMID:1274616", "title": "Temperature effects on the inflation reflex during expiratory time in the cat.", "content": "In order to obtain further information on the mechanisms controlling expiratory duration (TE) we have studied the effects of changes in body temperature on reflex characteristics of the TE-prolonging inflation reflex. In cats under light pentobarbitone anesthesia controlled volume changes were applied at various times in expiration and the changes in TE were measured from records of phrenic activity. Inflations falling in the last 20% of the control expiratory time were without effect. This reflex insensitive phase remained a constant fraction of expiratory time when respiratory rate was changed with temperature. The relative reflex responsiveness increased, and the volume threshold was reduced with increasing respiratory rate. The inflation reflex characteristics showed integration of the incoming pulmonary stretch receptor activity. The integrating mechanism exhibited a \"leaky\" character, the decay rate of which changed with body temperature. Functionally the duration of the inspiration-inhibiting activity controlling expiratory duration can be regarded as dependent on 3 main factors 1) the initial peak level of the inhibitory activity, 2) the amount and timing of the vagal afferent activity which adds to this inhibition, and 3) its rate of decay. The results suggest that all these factors are influenced by changes in temperature.", "contents": "Temperature effects on the inflation reflex during expiratory time in the cat. In order to obtain further information on the mechanisms controlling expiratory duration (TE) we have studied the effects of changes in body temperature on reflex characteristics of the TE-prolonging inflation reflex. In cats under light pentobarbitone anesthesia controlled volume changes were applied at various times in expiration and the changes in TE were measured from records of phrenic activity. Inflations falling in the last 20% of the control expiratory time were without effect. This reflex insensitive phase remained a constant fraction of expiratory time when respiratory rate was changed with temperature. The relative reflex responsiveness increased, and the volume threshold was reduced with increasing respiratory rate. The inflation reflex characteristics showed integration of the incoming pulmonary stretch receptor activity. The integrating mechanism exhibited a \"leaky\" character, the decay rate of which changed with body temperature. Functionally the duration of the inspiration-inhibiting activity controlling expiratory duration can be regarded as dependent on 3 main factors 1) the initial peak level of the inhibitory activity, 2) the amount and timing of the vagal afferent activity which adds to this inhibition, and 3) its rate of decay. The results suggest that all these factors are influenced by changes in temperature."} {"id": "PMID:1274617", "title": "Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. II. Effects from segmental flexor reflex pathways.", "content": "Interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as \"Ia inhibitory interneurones\") were recorded in the lumbar spinal cord of the cat. Volleys in ipsilateral and contralateral high threshold muscle afferents, cutaneous and high threshold joint afferents evoked a mixture of polysynaptic excitation and inhibition. These effects were ascribed to pathways activated by flexor reflex afferents (FRA) and in addition a specific ipsilateral low threshold cutaneous pathway. Ia inhibitory interneurones excited monosynaptically from flexor nerves received stronger net excitation by volleys in ipsilateral FRA than did extensor coupled interneurones, while the opposite pattern was seen from the contralateral FRA. These patterns are similar to those found in flexor and extensor motoneurones respectivey. The FRA inhibition in Ia inhibitory interneurones was partly mediated by \"opposite\" Ia inhibitory interneurones, i.e. those which are mediating the Ia inhibition of Ia inhibitory interneurones. The extent to which the FRA inhibition is transmitted by Ia inhibitory interneurones was roughly estimated by its susceptibility to recurrent depression by antidromic ventral root stimulation. The main conclusion is that most segmental pathways seem to evoke their effects in parallel to motoneurones and Ia inhibitory interneurones which are monosynaptically linked to the same muscle. The functional importance of this conclusion is discussed in a following report.", "contents": "Convergence on interneurones mediating the reciprocal Ia inhibition of motoneurones. II. Effects from segmental flexor reflex pathways. Interneurones identified as mediating the disynaptic reciprocal Ia inhibition of motoneurones (referred to as \"Ia inhibitory interneurones\") were recorded in the lumbar spinal cord of the cat. Volleys in ipsilateral and contralateral high threshold muscle afferents, cutaneous and high threshold joint afferents evoked a mixture of polysynaptic excitation and inhibition. These effects were ascribed to pathways activated by flexor reflex afferents (FRA) and in addition a specific ipsilateral low threshold cutaneous pathway. Ia inhibitory interneurones excited monosynaptically from flexor nerves received stronger net excitation by volleys in ipsilateral FRA than did extensor coupled interneurones, while the opposite pattern was seen from the contralateral FRA. These patterns are similar to those found in flexor and extensor motoneurones respectivey. The FRA inhibition in Ia inhibitory interneurones was partly mediated by \"opposite\" Ia inhibitory interneurones, i.e. those which are mediating the Ia inhibition of Ia inhibitory interneurones. The extent to which the FRA inhibition is transmitted by Ia inhibitory interneurones was roughly estimated by its susceptibility to recurrent depression by antidromic ventral root stimulation. The main conclusion is that most segmental pathways seem to evoke their effects in parallel to motoneurones and Ia inhibitory interneurones which are monosynaptically linked to the same muscle. The functional importance of this conclusion is discussed in a following report."} {"id": "PMID:1274618", "title": "Transfer of I125-albumin from blood into brain and cerebrospinal fluid in newborn and juvenile rats.", "content": "Human fetuses, rabbit fetuses and newborn rats have a relatively high concentration of protein in cerebrospinal fluid (csf) as compared with the adult. The present study was undertaken in an attempt to evaluate whether this high protein concentration in newborn rats is caused by a high permeability of the blood-brain-csf barrier to protein or by a low production rate of csf. The results suggest that the high concentration protein in csf in newborn rats is due to a low rate of production of csf rather than to an increased transfer of protein across the blood-brain-csf barrier.", "contents": "Transfer of I125-albumin from blood into brain and cerebrospinal fluid in newborn and juvenile rats. Human fetuses, rabbit fetuses and newborn rats have a relatively high concentration of protein in cerebrospinal fluid (csf) as compared with the adult. The present study was undertaken in an attempt to evaluate whether this high protein concentration in newborn rats is caused by a high permeability of the blood-brain-csf barrier to protein or by a low production rate of csf. The results suggest that the high concentration protein in csf in newborn rats is due to a low rate of production of csf rather than to an increased transfer of protein across the blood-brain-csf barrier."} {"id": "PMID:1274619", "title": "Inhibition of reserpine, guanethidine and imiparmine of the uptake of 5-hydroxytryptamine by rat peritoneal mast cells in vitro.", "content": "The effect of reserpine, guanethidine and imipramine of the uptake of tritiated 5-hydroxytryptamine by rat peritoneal mast cells was studied in vitro. The Km value for uptake of 5-hydroxytryptamine was 3 x 10(-7) M in this study. Kinetic analysis of the data obtained suggests that the drugs inhibits the uptake in a competitive manner, in the order of decreasing potency: reserpine, imipramine, guanethidine. For reserpine the Dixon plot resulted in two curves, each composed of 2 linear components suggesting inhibition of uptake of 5-hydroxytryptamine at 2 different levels or by 2 different mechanisms with different K1 values. It is suggested that the higher K1 value, representing an immediate effect of reserpine, stands for inhibition of uptake at the cell membrane. The lower K1 value possibly represents inhibition at the level of the membrane surrounding the intracellular storage organelles.", "contents": "Inhibition of reserpine, guanethidine and imiparmine of the uptake of 5-hydroxytryptamine by rat peritoneal mast cells in vitro. The effect of reserpine, guanethidine and imipramine of the uptake of tritiated 5-hydroxytryptamine by rat peritoneal mast cells was studied in vitro. The Km value for uptake of 5-hydroxytryptamine was 3 x 10(-7) M in this study. Kinetic analysis of the data obtained suggests that the drugs inhibits the uptake in a competitive manner, in the order of decreasing potency: reserpine, imipramine, guanethidine. For reserpine the Dixon plot resulted in two curves, each composed of 2 linear components suggesting inhibition of uptake of 5-hydroxytryptamine at 2 different levels or by 2 different mechanisms with different K1 values. It is suggested that the higher K1 value, representing an immediate effect of reserpine, stands for inhibition of uptake at the cell membrane. The lower K1 value possibly represents inhibition at the level of the membrane surrounding the intracellular storage organelles."} {"id": "PMID:1274621", "title": "The vagal control of the ileo-cecal sphincter in the cat.", "content": "In acute experiments on chloralosed cats the effect of efferent cervical vagal stimulation on a flow through the ileo-cecal sphincter (ICS) was studied. The motor activity of the jejunum, ileum and large intestine adjacent to the sphincter was recorded simultaneously. Vagal stimulation caused a decrease in the transphincteric flow and increased motor activity in the ileum. Increased motor activity in the proximal colon was recorded only occasionally. When the vagal nerves were stimulated during continuous splachine stimulation the transsphincteric flow was decreased although the tone and motility of the ileum was suppressed. Furthermore, guanethidine (1-3 mg/kg b.w.) blocked or suppressed the effect of vagal stimulation on the transsphincteric flow while the excitatory response of the proximal colon was greatly enhanced. This indicates that the reduction of the transsphinctteric flow following vagal stimulation was at least partly due to a direct effect of the vagal nerves on the sphincteric muscle and not to a squeezing effect of that part of the colonic wall that surrounds the sphincter. Atropine (0.1 and 1 mg/kg b.w.) blocked all responses to vagal stimulation. Thus, both guanethidine and atropine blocked the vagally induced contraction of the ICS. Relaxation to the ICS was never obtained by vagal stimulation even when the tone of the sphincter had been increased by infusion of noradrenaline.", "contents": "The vagal control of the ileo-cecal sphincter in the cat. In acute experiments on chloralosed cats the effect of efferent cervical vagal stimulation on a flow through the ileo-cecal sphincter (ICS) was studied. The motor activity of the jejunum, ileum and large intestine adjacent to the sphincter was recorded simultaneously. Vagal stimulation caused a decrease in the transphincteric flow and increased motor activity in the ileum. Increased motor activity in the proximal colon was recorded only occasionally. When the vagal nerves were stimulated during continuous splachine stimulation the transsphincteric flow was decreased although the tone and motility of the ileum was suppressed. Furthermore, guanethidine (1-3 mg/kg b.w.) blocked or suppressed the effect of vagal stimulation on the transsphincteric flow while the excitatory response of the proximal colon was greatly enhanced. This indicates that the reduction of the transsphinctteric flow following vagal stimulation was at least partly due to a direct effect of the vagal nerves on the sphincteric muscle and not to a squeezing effect of that part of the colonic wall that surrounds the sphincter. Atropine (0.1 and 1 mg/kg b.w.) blocked all responses to vagal stimulation. Thus, both guanethidine and atropine blocked the vagally induced contraction of the ICS. Relaxation to the ICS was never obtained by vagal stimulation even when the tone of the sphincter had been increased by infusion of noradrenaline."} {"id": "PMID:1274622", "title": "A computer program for an open two compartment system distinguishing three models.", "content": "A digital computer program is described for the estimation of parameters in an open two compartment system distinguishing 3 models. The mathematical function to be fitted to a given set of experimental data is given initial estimates for the parameters of the function. The program uses an iterative procedure to adjust the parameters until the sum of squares of residuals has converged to a minimum. Assuming that a given substance is introduced into compartment 1, the function can be fitted to the set of experiment data of that compartment. A set of experimental data from compartment 2 can also be included in the minimizing function. Two optional weighting functions are presented. From the constants of the two-exponential functions the physiological parameters of the three models are determined. Experimental observations of compartment 1 only allow for calculation of physiological parameters of two of the models.", "contents": "A computer program for an open two compartment system distinguishing three models. A digital computer program is described for the estimation of parameters in an open two compartment system distinguishing 3 models. The mathematical function to be fitted to a given set of experimental data is given initial estimates for the parameters of the function. The program uses an iterative procedure to adjust the parameters until the sum of squares of residuals has converged to a minimum. Assuming that a given substance is introduced into compartment 1, the function can be fitted to the set of experiment data of that compartment. A set of experimental data from compartment 2 can also be included in the minimizing function. Two optional weighting functions are presented. From the constants of the two-exponential functions the physiological parameters of the three models are determined. Experimental observations of compartment 1 only allow for calculation of physiological parameters of two of the models."} {"id": "PMID:1274623", "title": "The effect of local application of vinblastine or cholchinine on acetylcholine accumulation in rat sciatic nerve.", "content": "The accumulation of acetylcholine (ACh) following nerve crush was inhibited by high concentration of colchicine (10(-1), 10(-2 M) and vinblastine (10(-2)-10(-4 M) in a dose-dependent manner. The two mitotic inhibitors were effective both when applied to axons (subepineural injections) and to perikaraya (injections into the lumbar intumescence). The results indicate that mitotic inhibitors, when applied locally to cholinergic motor neurons, may block the proximo-distal transport of ACh. The possibility is discussed that this blockade is caused by an interference with a microtubule mechanism in the axons. Evidence for an increased local synthesis of ACh near the site of injection into nerves also obtained with the highest concentrations of either substance used.", "contents": "The effect of local application of vinblastine or cholchinine on acetylcholine accumulation in rat sciatic nerve. The accumulation of acetylcholine (ACh) following nerve crush was inhibited by high concentration of colchicine (10(-1), 10(-2 M) and vinblastine (10(-2)-10(-4 M) in a dose-dependent manner. The two mitotic inhibitors were effective both when applied to axons (subepineural injections) and to perikaraya (injections into the lumbar intumescence). The results indicate that mitotic inhibitors, when applied locally to cholinergic motor neurons, may block the proximo-distal transport of ACh. The possibility is discussed that this blockade is caused by an interference with a microtubule mechanism in the axons. Evidence for an increased local synthesis of ACh near the site of injection into nerves also obtained with the highest concentrations of either substance used."} {"id": "PMID:1274624", "title": "Release of vitamin B12-binding protein from isolated rat liver perfused with a synthetic medium.", "content": "The unsaturated vitamin B12-binding capacity (UBBC) of the small molecular size vitamin B12-binding protein (SBP) release and albumin release into the medium and the fluid pressure in the portal vein were studied with respect to their ability to reflect the state of isolated perfused rat liver. The liver was perfused in vitro with a synthetic medium either with or without a gas carrier. Liver damage was induced by hypoxia or noradrenalin. Variations in experimental conditions resulted in different patterns of parameters reflecting different aspects of the liver state. The fluid pressure in the portal vein reflected sensitively the circulatory state but is not always a criterion of the general condition of the isolated liver. The albumin release is a criterion of functional state but did not always reflect liver damage. However, the amount of UBBC of SBP released into the medium is a parameter reflecting sensitively the functional capacity of the liver to produce protein and also seems to indicate liver damage. The use of this parameter provides supplementary information that cannot be obtained by either of the two more conventional parameters.", "contents": "Release of vitamin B12-binding protein from isolated rat liver perfused with a synthetic medium. The unsaturated vitamin B12-binding capacity (UBBC) of the small molecular size vitamin B12-binding protein (SBP) release and albumin release into the medium and the fluid pressure in the portal vein were studied with respect to their ability to reflect the state of isolated perfused rat liver. The liver was perfused in vitro with a synthetic medium either with or without a gas carrier. Liver damage was induced by hypoxia or noradrenalin. Variations in experimental conditions resulted in different patterns of parameters reflecting different aspects of the liver state. The fluid pressure in the portal vein reflected sensitively the circulatory state but is not always a criterion of the general condition of the isolated liver. The albumin release is a criterion of functional state but did not always reflect liver damage. However, the amount of UBBC of SBP released into the medium is a parameter reflecting sensitively the functional capacity of the liver to produce protein and also seems to indicate liver damage. The use of this parameter provides supplementary information that cannot be obtained by either of the two more conventional parameters."} {"id": "PMID:1274625", "title": "Gravitational stress and autonomic cardiac blockade.", "content": "Arterial pressure, heart rate and cardiac output were recorded in eight healthy, male volunteers in the sitting position at normal gravity (1 G) and during a 4 min exposure in a human centrifuge to 3 G, the G vector in both conditions acting in the head-foot direction. The responses of the observed variables to the change from 1 G to 3 G were compared before and after combined beta-adrenergic and parasympathetic blockade of the heart induced by the i.v. administration of propranolol, 0.25 mg/kg bwt, and atropine, 0.03 mg/kg bwt. After blockade the heart-rate response to increased G averaged 22% of that observed without blockade. Mean arterial pressure at 3 G, and thus G tolerance, was significantly lowered after blockade, resulting in symptoms of retinal hypoxia (\"greyout\") towards the end of the 3 G runs in some of the subjects. G-induced reductions in cardiac output and stroke volume were significantly larger after blockade. Associated increases in total peripheral resistance were 56% before and 79% after blockade, the stronger vasoconstrictor response in the latter case thus being insufficient for maintenance of arterial pressure homeostasis.", "contents": "Gravitational stress and autonomic cardiac blockade. Arterial pressure, heart rate and cardiac output were recorded in eight healthy, male volunteers in the sitting position at normal gravity (1 G) and during a 4 min exposure in a human centrifuge to 3 G, the G vector in both conditions acting in the head-foot direction. The responses of the observed variables to the change from 1 G to 3 G were compared before and after combined beta-adrenergic and parasympathetic blockade of the heart induced by the i.v. administration of propranolol, 0.25 mg/kg bwt, and atropine, 0.03 mg/kg bwt. After blockade the heart-rate response to increased G averaged 22% of that observed without blockade. Mean arterial pressure at 3 G, and thus G tolerance, was significantly lowered after blockade, resulting in symptoms of retinal hypoxia (\"greyout\") towards the end of the 3 G runs in some of the subjects. G-induced reductions in cardiac output and stroke volume were significantly larger after blockade. Associated increases in total peripheral resistance were 56% before and 79% after blockade, the stronger vasoconstrictor response in the latter case thus being insufficient for maintenance of arterial pressure homeostasis."} {"id": "PMID:1274626", "title": "Interaction between the hypothalamic defence reaction and cardiac ventricular receptor reflexes.", "content": "The interference with regard to the cardiovascular and gastric motility responses which follows stimulation of the hypothalamic defence area (D.A.) and a simultaneous afferent input from cardiac ventricular receptors was analysed in chloralose-anesthetized cats. In spinalized animals with only the vagal efferent innervation of autonomic effectors from supraspinal structures intact, a D.A. stimulation increased the heart rate to the same level irrespective whether the cardiac receptor afferents were stimulated or not. This suggests that the vagal component of the reflex bradycardia of cardiac receptor origin was completely suppressed by the D.A. stimulation. The reflex gastric relaxation to cardiac receptor activation, mediated via vagal efferent non-adrenergic fibres, was similarly completely blocked by D.A. stimulation. In contrast, the reflex inhibition of the sympathetic outflow to the heart and vessels from cardiac receptors was still effective during a D.A. stimulation, a phenomenon which seems compatible with a simple summation of excitatory D.A. and inhibitory cardiac receptor influences on the sympathetic neurons. The modifying influence from ventricular receptors on D.A. responses closely resembles that exerted by the arterial baroreceptors. The two reflex mechanisms thus work in concert and synergistically with the hypothalamic influences to produce maximal cardiac output and skeletal muscle perfusion without undue increases of pressure load on the pump during a defence reaction.", "contents": "Interaction between the hypothalamic defence reaction and cardiac ventricular receptor reflexes. The interference with regard to the cardiovascular and gastric motility responses which follows stimulation of the hypothalamic defence area (D.A.) and a simultaneous afferent input from cardiac ventricular receptors was analysed in chloralose-anesthetized cats. In spinalized animals with only the vagal efferent innervation of autonomic effectors from supraspinal structures intact, a D.A. stimulation increased the heart rate to the same level irrespective whether the cardiac receptor afferents were stimulated or not. This suggests that the vagal component of the reflex bradycardia of cardiac receptor origin was completely suppressed by the D.A. stimulation. The reflex gastric relaxation to cardiac receptor activation, mediated via vagal efferent non-adrenergic fibres, was similarly completely blocked by D.A. stimulation. In contrast, the reflex inhibition of the sympathetic outflow to the heart and vessels from cardiac receptors was still effective during a D.A. stimulation, a phenomenon which seems compatible with a simple summation of excitatory D.A. and inhibitory cardiac receptor influences on the sympathetic neurons. The modifying influence from ventricular receptors on D.A. responses closely resembles that exerted by the arterial baroreceptors. The two reflex mechanisms thus work in concert and synergistically with the hypothalamic influences to produce maximal cardiac output and skeletal muscle perfusion without undue increases of pressure load on the pump during a defence reaction."} {"id": "PMID:1274627", "title": "The effects of neuraminidase and protamine chloride on potential clamp parameters of the node of Ranvier (Xenopus laevis).", "content": "The effects of neuraminidase and protamine chloride on the ionic currents associated with step changes in membrane potential were studied. Neuraminidase (a hydrolase which cleaves glycosidically bound sialic acid) had negligible effects on the permeability properties. The polycation protamine chloride decreased the sodium as well as the potassium currents. The sodium equilibrium potential decreased during the experiments which indicates a gain in internal sodium concentration. The analysis showed that the effects on the currents were caused by a decrease of the specific permeability changes. No shift along the potential axis of the potential dependent parameters was observed.", "contents": "The effects of neuraminidase and protamine chloride on potential clamp parameters of the node of Ranvier (Xenopus laevis). The effects of neuraminidase and protamine chloride on the ionic currents associated with step changes in membrane potential were studied. Neuraminidase (a hydrolase which cleaves glycosidically bound sialic acid) had negligible effects on the permeability properties. The polycation protamine chloride decreased the sodium as well as the potassium currents. The sodium equilibrium potential decreased during the experiments which indicates a gain in internal sodium concentration. The analysis showed that the effects on the currents were caused by a decrease of the specific permeability changes. No shift along the potential axis of the potential dependent parameters was observed."} {"id": "PMID:1274628", "title": "Effects of gonadotrophins on the cumulus oophorus of isolated rat Graafian follicles.", "content": "Graafian follicles were extirpated before the endogenous LH surge on the day prior to ovulation from PMS-injected immature rats. They were incubated in chemically defined medium in presence or absence of gonadotrophins for 4-10 h. After incubation the oocyte-cumulus complexes were recovered from the follicles and one group inspected by Nomarski interference contrast microscopy and one group was placed in saline containing hyaluronidase. In hormone-free medium both the oocyte and the cumulus cells remained morphologically unchanged: a dictyate oocyte surrounded by a compact mass of cumulus cells. Hyaluronidase did not detach cells from the cumulus structure. However, in presence of LH or FSH morphological changes developed in both cell types: the oocyte resumed meiosis as revealed by germinal vesicle breakdown and polar body formation; the cumulus structure became dispersed and embedded in a viscous matrix. The individual cumulus cells displayed pseudopodia-like processes of the cell surface. Treatment with hyaluronidase resulted in detachment of cells from the cumulus. The effects of LH described on the oocyte and cumulus cells were unimpaired in presence of cyanoketone or aminoglutethimide although these agents blocked the follicular relase of progesterone, estradiol and androstenedione as revealed by RIA. The results indicate that a close functional relationship exists between the two cell types of the cumulus oophorus, the oocyte and the cumulus granulosa cells. Both cell types are affected directly or indirectly by gonadotrophins and characteristical morphological changes develop synchronously in both cell types.", "contents": "Effects of gonadotrophins on the cumulus oophorus of isolated rat Graafian follicles. Graafian follicles were extirpated before the endogenous LH surge on the day prior to ovulation from PMS-injected immature rats. They were incubated in chemically defined medium in presence or absence of gonadotrophins for 4-10 h. After incubation the oocyte-cumulus complexes were recovered from the follicles and one group inspected by Nomarski interference contrast microscopy and one group was placed in saline containing hyaluronidase. In hormone-free medium both the oocyte and the cumulus cells remained morphologically unchanged: a dictyate oocyte surrounded by a compact mass of cumulus cells. Hyaluronidase did not detach cells from the cumulus structure. However, in presence of LH or FSH morphological changes developed in both cell types: the oocyte resumed meiosis as revealed by germinal vesicle breakdown and polar body formation; the cumulus structure became dispersed and embedded in a viscous matrix. The individual cumulus cells displayed pseudopodia-like processes of the cell surface. Treatment with hyaluronidase resulted in detachment of cells from the cumulus. The effects of LH described on the oocyte and cumulus cells were unimpaired in presence of cyanoketone or aminoglutethimide although these agents blocked the follicular relase of progesterone, estradiol and androstenedione as revealed by RIA. The results indicate that a close functional relationship exists between the two cell types of the cumulus oophorus, the oocyte and the cumulus granulosa cells. Both cell types are affected directly or indirectly by gonadotrophins and characteristical morphological changes develop synchronously in both cell types."} {"id": "PMID:1274629", "title": "Glucose consumption in rat cerbral cortex in normoxia, hypoxia and hypercapnia.", "content": "Glucose consumption was measured in the cerebral cortex of rats, anesthetized with 70% N20, under normoxic conditions, as well as in hypoxia (Pao2 about 25 mmHg) and hypercapnia (Paco2 80-85 mmHg). The method used was that Hawkins et al (1974), modified to allow studies of transients in glycolytic rate. Cortical glucose consumption in normoxia was 0.77 mumol-g(-1)-min(-1). It is concluded that whereas glucose consumption in the whole brain of unanesthetized rat may be close to 0.6 mumol-g(-1)-min(-1), that of the cerebral cortex is close to 0.8 mumol-g(-1)-min(-1). During the first 2 min of hypoxia, glucose consumption was increased to twice the normal, and during the fist 2 min of hypercapnia, the corresponding value was less thane third of the normal. After 15 min of hypoxia, the glucose consumption had returned towards control values. In \"steady state\" hypercapnia, the glycolytic flux was higher than in the inital phase although still below normocapnic values.", "contents": "Glucose consumption in rat cerbral cortex in normoxia, hypoxia and hypercapnia. Glucose consumption was measured in the cerebral cortex of rats, anesthetized with 70% N20, under normoxic conditions, as well as in hypoxia (Pao2 about 25 mmHg) and hypercapnia (Paco2 80-85 mmHg). The method used was that Hawkins et al (1974), modified to allow studies of transients in glycolytic rate. Cortical glucose consumption in normoxia was 0.77 mumol-g(-1)-min(-1). It is concluded that whereas glucose consumption in the whole brain of unanesthetized rat may be close to 0.6 mumol-g(-1)-min(-1), that of the cerebral cortex is close to 0.8 mumol-g(-1)-min(-1). During the first 2 min of hypoxia, glucose consumption was increased to twice the normal, and during the fist 2 min of hypercapnia, the corresponding value was less thane third of the normal. After 15 min of hypoxia, the glucose consumption had returned towards control values. In \"steady state\" hypercapnia, the glycolytic flux was higher than in the inital phase although still below normocapnic values."} {"id": "PMID:1274631", "title": "Blood flow changes in the submaxillary gland of the rat on parasympathetic and sympathetic nerve stimulation.", "content": "Blood flow and secretion from the submaxillary gland of the rat was recorded. Stimulation of the chordalingual nerve evoked vasodilatation which was little, it at all, decreased after administration of atropine. The secretion evoked on parasympathetic nerve stimulation was greatly reduced but not totally abolished by parasympatholytic agents. Stimulation of the cervical sympathetic trunk evoked secretion, which was mediated both via alpha and beta-adrenoceptors and vasoconstriction which was abolished by dihydroergotamine, and thus seemed to be mediated via alpha-adrenergic receptors. After alpha-adrenoceptor blockade vasodilatation was seen on sympathetic nerve stimulation. This was abolished by the beta-adrenoceptor blocking agent propranolol.", "contents": "Blood flow changes in the submaxillary gland of the rat on parasympathetic and sympathetic nerve stimulation. Blood flow and secretion from the submaxillary gland of the rat was recorded. Stimulation of the chordalingual nerve evoked vasodilatation which was little, it at all, decreased after administration of atropine. The secretion evoked on parasympathetic nerve stimulation was greatly reduced but not totally abolished by parasympatholytic agents. Stimulation of the cervical sympathetic trunk evoked secretion, which was mediated both via alpha and beta-adrenoceptors and vasoconstriction which was abolished by dihydroergotamine, and thus seemed to be mediated via alpha-adrenergic receptors. After alpha-adrenoceptor blockade vasodilatation was seen on sympathetic nerve stimulation. This was abolished by the beta-adrenoceptor blocking agent propranolol."} {"id": "PMID:1274632", "title": "The origin of impulses recorded from dentinal cavities in the tooth of the cat.", "content": "Intradental nerve impulse activity can be recorded by means of electrodes inserted into dentinal cavities in the tooth of the cat. The following study has been conducted to investigate the origin ofthis impulse activity. The results suggest that the fibres from which the impulses are recorded must pass through the major part ofthe pulp between the recording electrodes. Furthermore, the results show that it is not possible to record discharges in the finest terminal branches in thepulpo-dentinal border zone using the present technique. However, the data obtained indicate that these terminal branches were activated during stimulation resulting in recordable propagated axonal impulses.", "contents": "The origin of impulses recorded from dentinal cavities in the tooth of the cat. Intradental nerve impulse activity can be recorded by means of electrodes inserted into dentinal cavities in the tooth of the cat. The following study has been conducted to investigate the origin ofthis impulse activity. The results suggest that the fibres from which the impulses are recorded must pass through the major part ofthe pulp between the recording electrodes. Furthermore, the results show that it is not possible to record discharges in the finest terminal branches in thepulpo-dentinal border zone using the present technique. However, the data obtained indicate that these terminal branches were activated during stimulation resulting in recordable propagated axonal impulses."} {"id": "PMID:1274633", "title": "Metabolic reactions to changes in core and skin temperature in man.", "content": "The metabolic cold response, i.e. the increase in oxygen consumption above that for the given activity in a neutral environment, was measured in 7 subjects during cooling, resting or swimming in cold water (14, 16, 18, 20degrees C) and during rewarming in air (Ta 20, 30, 40degrees C), bicycling or resting. Esophageal temperatures varied between 38 and 34degrees C. Mean skin temperature was considered as equal to water temperature during cooling, and ranged between 25-35degrees C during rewarming in the different environments. Both central and peripheral cold stimulation induced metabolic cold responses. The skin temperature was the dominating factor in determining the response, especially in transient states. During rewarding a rising skin temperature suppressed the effects of even very low core temperatures.", "contents": "Metabolic reactions to changes in core and skin temperature in man. The metabolic cold response, i.e. the increase in oxygen consumption above that for the given activity in a neutral environment, was measured in 7 subjects during cooling, resting or swimming in cold water (14, 16, 18, 20degrees C) and during rewarming in air (Ta 20, 30, 40degrees C), bicycling or resting. Esophageal temperatures varied between 38 and 34degrees C. Mean skin temperature was considered as equal to water temperature during cooling, and ranged between 25-35degrees C during rewarming in the different environments. Both central and peripheral cold stimulation induced metabolic cold responses. The skin temperature was the dominating factor in determining the response, especially in transient states. During rewarding a rising skin temperature suppressed the effects of even very low core temperatures."} {"id": "PMID:1274634", "title": "Cardiac receptors in ducks--a link between vasoconstruction and bradycardia during diving.", "content": "It has been demonstrated that cardiac receptors, most likely of the left ventricular type, are present also in the duck's heart. These receptors and their reflex responses (i.e. bradycardia and hypotension) could be blocked by intrapericardial administration of lidocaine. Initially, usch receptor blockade did not affect efferent vagal control of heart rate, as revealed by undiminished bradycardia in response to a standardized vagal stimulation. After cardiac receptor blockade, however, the duck's normal bradycardia response to head immersion was greatly reduced. The cardiovascular response to submersion was now instead characterized by a marked rise in arterial pressure, with superimposed bouts of intensified bradycardia and pressure reduction, evidently induced reflexly from the arterial baroreceptors. Meanwhile, the bradycardia response to standarized efferent vagal stimulation was still the same as before intrapericardial lidocaine injection. These results suggest that the marked rise in cardiac filling pressure following the intense shemo-receptor-induced constriction of both resistance and capacitance vessels, activates ventricular stretch receptors signalling in vagal afferents. Apparently, the activation of these receptors contributes crucially to the bradycardia and reduction of cardial output, which balance off the greatly increased peripheral resistance in the diving duck.", "contents": "Cardiac receptors in ducks--a link between vasoconstruction and bradycardia during diving. It has been demonstrated that cardiac receptors, most likely of the left ventricular type, are present also in the duck's heart. These receptors and their reflex responses (i.e. bradycardia and hypotension) could be blocked by intrapericardial administration of lidocaine. Initially, usch receptor blockade did not affect efferent vagal control of heart rate, as revealed by undiminished bradycardia in response to a standardized vagal stimulation. After cardiac receptor blockade, however, the duck's normal bradycardia response to head immersion was greatly reduced. The cardiovascular response to submersion was now instead characterized by a marked rise in arterial pressure, with superimposed bouts of intensified bradycardia and pressure reduction, evidently induced reflexly from the arterial baroreceptors. Meanwhile, the bradycardia response to standarized efferent vagal stimulation was still the same as before intrapericardial lidocaine injection. These results suggest that the marked rise in cardiac filling pressure following the intense shemo-receptor-induced constriction of both resistance and capacitance vessels, activates ventricular stretch receptors signalling in vagal afferents. Apparently, the activation of these receptors contributes crucially to the bradycardia and reduction of cardial output, which balance off the greatly increased peripheral resistance in the diving duck."} {"id": "PMID:1274635", "title": "Protein synthesis with special reference to S-100 protein in brain slices from rats receiving a restricted protein supply.", "content": "The synthesis of S-100 protein and that of soluble and total proteins was investigated using cerebral slices from rats fed a 20% or 3% protein containing diet for 6 days. Incorporation of radioactive amino acids into S-100 protein was significantly higher when rats were fed a diet containing 20% protein. No significant differences were obtained in the radioactivity incorporated into total or soluble proteins between the 2 dietary groups. 14C-leucine of aspecific radioactivity of 55 mCi/mmol or 3.2 mCi/mmol incorporated with time into total protein was similar for the 2 dietary groups. The time-dependent uptake of 14C-leucine by the slices and theinulin space remained unaffected by the dietary conditions used; and amino acid analyser estimates of the free amino acid pool showed no significant differences. Brain wet weight was 1.54+/-0.02 g and1.39+/-0.02 g for protein-fed and protein-restricted rats respectively. The corresponding body weight increased by 7.8 g/day or fell by 0.5 g/day. Although the differences observed in total protein synthesis were small the synthesis of a nervous tissue specific protein S-100 was markedly affected by short-term protein restriction.", "contents": "Protein synthesis with special reference to S-100 protein in brain slices from rats receiving a restricted protein supply. The synthesis of S-100 protein and that of soluble and total proteins was investigated using cerebral slices from rats fed a 20% or 3% protein containing diet for 6 days. Incorporation of radioactive amino acids into S-100 protein was significantly higher when rats were fed a diet containing 20% protein. No significant differences were obtained in the radioactivity incorporated into total or soluble proteins between the 2 dietary groups. 14C-leucine of aspecific radioactivity of 55 mCi/mmol or 3.2 mCi/mmol incorporated with time into total protein was similar for the 2 dietary groups. The time-dependent uptake of 14C-leucine by the slices and theinulin space remained unaffected by the dietary conditions used; and amino acid analyser estimates of the free amino acid pool showed no significant differences. Brain wet weight was 1.54+/-0.02 g and1.39+/-0.02 g for protein-fed and protein-restricted rats respectively. The corresponding body weight increased by 7.8 g/day or fell by 0.5 g/day. Although the differences observed in total protein synthesis were small the synthesis of a nervous tissue specific protein S-100 was markedly affected by short-term protein restriction."} {"id": "PMID:1274636", "title": "Pathways for chloride and sodium transport across toad skin.", "content": "The voltage dependecies of Na and Cl fluxes were investigated in the isolated toad skin. With Cl-Ringer's on both sides Cl outflux varied very little with clamping voltage. The same was true for the influx of Cl at depolarizing voltages (psii -psio lessthan0 mV), wheras hyperpolarization led to a marked increase in this flux. A net chloride influx under short circuit conditions indicated active transport of chloride. The outflux of Cl was a saturable function of outside Cl concentration. The outflux of urea was hardly affected by raising outside Cl concentration, and the effect of varying outside nitrate concentration on Cl outflux was likewise small. Both influx and outflux could be inhibited partially bt acetazolamide. The outflux of Na varied with the clamping voltage as would be expected for an ion transported by electrodiffusion, and it was shown that amiloride had no effect on Na outflux, so it was concluded that the Na outflux route is particular. In the absence of Cl in the outside solution a small outflux of Cl persists. Also this flux varied with the clamping voltage according to laws for electrodiffusion. The variation of the ratio of sodium outflux to chloride outflux with clamping voltage indicated free passive diffusion of both these ions under the conditions mentioned. A comparison of the outfluxes of Na and Cl in skins bathed with gluconate Ringer's outside showed that the outflux route of these two ions was cation selective (PNa/PCl=1.88). When the paracellular leak pathway of the skins was opened by exposing the outside to hyperosmolar urea solutions, the ratio of the transport numbers was found to be TNa/TCl=1.71. The roles of the two ions in determining the steady state current-voltage relationships were compared. At hyperpolarizing voltages most or all of the clamping current was carried by an inward Cl flux. By depolarization sodium influx plays an increasing role with increasing depolarization. Under short circuit conditions active chloride transport was found to contribute to the short circuit current.", "contents": "Pathways for chloride and sodium transport across toad skin. The voltage dependecies of Na and Cl fluxes were investigated in the isolated toad skin. With Cl-Ringer's on both sides Cl outflux varied very little with clamping voltage. The same was true for the influx of Cl at depolarizing voltages (psii -psio lessthan0 mV), wheras hyperpolarization led to a marked increase in this flux. A net chloride influx under short circuit conditions indicated active transport of chloride. The outflux of Cl was a saturable function of outside Cl concentration. The outflux of urea was hardly affected by raising outside Cl concentration, and the effect of varying outside nitrate concentration on Cl outflux was likewise small. Both influx and outflux could be inhibited partially bt acetazolamide. The outflux of Na varied with the clamping voltage as would be expected for an ion transported by electrodiffusion, and it was shown that amiloride had no effect on Na outflux, so it was concluded that the Na outflux route is particular. In the absence of Cl in the outside solution a small outflux of Cl persists. Also this flux varied with the clamping voltage according to laws for electrodiffusion. The variation of the ratio of sodium outflux to chloride outflux with clamping voltage indicated free passive diffusion of both these ions under the conditions mentioned. A comparison of the outfluxes of Na and Cl in skins bathed with gluconate Ringer's outside showed that the outflux route of these two ions was cation selective (PNa/PCl=1.88). When the paracellular leak pathway of the skins was opened by exposing the outside to hyperosmolar urea solutions, the ratio of the transport numbers was found to be TNa/TCl=1.71. The roles of the two ions in determining the steady state current-voltage relationships were compared. At hyperpolarizing voltages most or all of the clamping current was carried by an inward Cl flux. By depolarization sodium influx plays an increasing role with increasing depolarization. Under short circuit conditions active chloride transport was found to contribute to the short circuit current."} {"id": "PMID:1274637", "title": "Prostaglandin-mediated inhibition of noradrenaline release: its resistance to variations in rate of prostaglandine synthesis.", "content": "Isolated rabbit hearts were perfused according to Langendorff. The bilateral sympathetic nerve supply to the organ was stimulated at intervals, and the overflow of noradrenaline and of prostaglandins of the E series in the effluent was assayed, using fluorimetric and bioassay methods, respectively. The synthesis of prostaglandins in the organ was stimulated, either by perfusing the heart at a low pO2, or by infusing nicotinic acid. Hypoxia increased the coronary flow, provided the prostaglandin synthesis was not inhibited, probably as a consequence of hypoxia stimulation was however, unaffected by hypoxia. Nicotinic acid also stimulated prostaglandin formation, doubling the overflow of the lipid in response to nerve stimulation. In this series, too, the release of NA induced by nerve stimulation was unaffected by stimulation of prostaglandin synthesis. It is concluded that local variations in the rate of prostaglandin synthesis are unable to change the degree to which the release of sympathetic neurotransmitter is inhibited. Furthermore, it is suggested that the prostaglandin synthesis in rabbit heart takes place in compartments, separated functionally or morphologically.", "contents": "Prostaglandin-mediated inhibition of noradrenaline release: its resistance to variations in rate of prostaglandine synthesis. Isolated rabbit hearts were perfused according to Langendorff. The bilateral sympathetic nerve supply to the organ was stimulated at intervals, and the overflow of noradrenaline and of prostaglandins of the E series in the effluent was assayed, using fluorimetric and bioassay methods, respectively. The synthesis of prostaglandins in the organ was stimulated, either by perfusing the heart at a low pO2, or by infusing nicotinic acid. Hypoxia increased the coronary flow, provided the prostaglandin synthesis was not inhibited, probably as a consequence of hypoxia stimulation was however, unaffected by hypoxia. Nicotinic acid also stimulated prostaglandin formation, doubling the overflow of the lipid in response to nerve stimulation. In this series, too, the release of NA induced by nerve stimulation was unaffected by stimulation of prostaglandin synthesis. It is concluded that local variations in the rate of prostaglandin synthesis are unable to change the degree to which the release of sympathetic neurotransmitter is inhibited. Furthermore, it is suggested that the prostaglandin synthesis in rabbit heart takes place in compartments, separated functionally or morphologically."} {"id": "PMID:1274638", "title": "Prediction of propagation block on the basis of impulse shape in single unit recordings from human nerves.", "content": "The occurrence of impulse block was studied in single unit recordings and related to impulse shape when peripheral nerves were impaled with tungsten needle electrodes. Exposed nerves were exploited in frog and cat and non-exposed nerves in man. Three different impulse shapes were seen: 1. Negative spikes of very short durations which nearly all propagated. 2. Positive double peaked spikes which all propagated. 3. Positive single peaked spikes which were of two different natures: one which propagated and one which did not. The findings suggest that urinary impulses recorded witha needle electrode impaling the myelin are positive and single peaked when the injury is minimal. Gradually a propagation delay might develop at the site of impalement giving rise to a double peak. Later the propagation may be blocked which is seen as a drop out of the second peak. The collected sample of observations indicates that it was possible to predict in practically all cases whether the propagation was blocked or not from the shapes of the single unit impulses and their alterations as seen by the tungsten needle electrode.", "contents": "Prediction of propagation block on the basis of impulse shape in single unit recordings from human nerves. The occurrence of impulse block was studied in single unit recordings and related to impulse shape when peripheral nerves were impaled with tungsten needle electrodes. Exposed nerves were exploited in frog and cat and non-exposed nerves in man. Three different impulse shapes were seen: 1. Negative spikes of very short durations which nearly all propagated. 2. Positive double peaked spikes which all propagated. 3. Positive single peaked spikes which were of two different natures: one which propagated and one which did not. The findings suggest that urinary impulses recorded witha needle electrode impaling the myelin are positive and single peaked when the injury is minimal. Gradually a propagation delay might develop at the site of impalement giving rise to a double peak. Later the propagation may be blocked which is seen as a drop out of the second peak. The collected sample of observations indicates that it was possible to predict in practically all cases whether the propagation was blocked or not from the shapes of the single unit impulses and their alterations as seen by the tungsten needle electrode."} {"id": "PMID:1274639", "title": "Effect of vasodilating drugs on external carotid and pulpal blood flow in dogs: \"stealing\" of dental perfusion pressure.", "content": "Blood flow in the external cartoid artery (ECBF) and dental pulp (PBF) was measured during arterial infusion of vasodilators (isoprenaline, papaverine, acetylcholine and bradykinin). Systemic arterial pressure (AP) and local arterial pressure of the teeth (LAP) were recorded in a femoral and the lateral nasal artery respectively. All four vasodilators were found to increase ECBF and simultaneously reduce lateral nasal arterial pressure--or in other words-to STEAL\" PERFUSION PRESSURE FROM THE TEETH. AP remained practically unchanged whereas PBF was variably affected. During infusion of isoprenaline PBF decreased on average by 19% of control. Papaverine nearly doubled PBG, while bradykinin caused no consistent change. Great pulpal flow variations were often recorded during constant acetylcholine infusion rate. The variable effect of the four vasodilators on PBF could partly be explained by the fall in LAP. Calculated pulpal resistance (LAP/PBF) showed no consistent change during isoprenaline infusion, bradykinin caused a slight fall and papaverine reduced LAP/PBF by 49%. The experiments demonstrate that due to the \"stealing\" of dental perfusion pressure caused by vasodilation in the neighbouring tissues, the effect of vasodilators on pulpal resistance vessels cannot be estimated without knowledge of the pressure in the small arteries directly feeding the teeth.", "contents": "Effect of vasodilating drugs on external carotid and pulpal blood flow in dogs: \"stealing\" of dental perfusion pressure. Blood flow in the external cartoid artery (ECBF) and dental pulp (PBF) was measured during arterial infusion of vasodilators (isoprenaline, papaverine, acetylcholine and bradykinin). Systemic arterial pressure (AP) and local arterial pressure of the teeth (LAP) were recorded in a femoral and the lateral nasal artery respectively. All four vasodilators were found to increase ECBF and simultaneously reduce lateral nasal arterial pressure--or in other words-to STEAL\" PERFUSION PRESSURE FROM THE TEETH. AP remained practically unchanged whereas PBF was variably affected. During infusion of isoprenaline PBF decreased on average by 19% of control. Papaverine nearly doubled PBG, while bradykinin caused no consistent change. Great pulpal flow variations were often recorded during constant acetylcholine infusion rate. The variable effect of the four vasodilators on PBF could partly be explained by the fall in LAP. Calculated pulpal resistance (LAP/PBF) showed no consistent change during isoprenaline infusion, bradykinin caused a slight fall and papaverine reduced LAP/PBF by 49%. The experiments demonstrate that due to the \"stealing\" of dental perfusion pressure caused by vasodilation in the neighbouring tissues, the effect of vasodilators on pulpal resistance vessels cannot be estimated without knowledge of the pressure in the small arteries directly feeding the teeth."} {"id": "PMID:1274640", "title": "Aging of schizophrenic patients as seen through the Rorschach test.", "content": "The authors have repeated, on the average 29.7 years later, Rorschach test in 11 schizophrenic men and 19 schizophrenic women. This work was carried out in the course of a follow-up study of schizophrenics more than 65 years of age. Analysis of the records showed that the only differences between the first and second examinations were increases in animal and popular responses in old age. The authors have tried to relate these findings to the general trends of schizophrenic development in senescence.", "contents": "Aging of schizophrenic patients as seen through the Rorschach test. The authors have repeated, on the average 29.7 years later, Rorschach test in 11 schizophrenic men and 19 schizophrenic women. This work was carried out in the course of a follow-up study of schizophrenics more than 65 years of age. Analysis of the records showed that the only differences between the first and second examinations were increases in animal and popular responses in old age. The authors have tried to relate these findings to the general trends of schizophrenic development in senescence."} {"id": "PMID:1274641", "title": "Effect of brain injury on social adaptability. Longitudinal study on frequency of criminality.", "content": "The study tried to clarify social adaptability of persons with brain injuries by using a long-term criminal development as a criterion. Randomly chosen 507 subjects whose open injury originated from the Second World War were followed up for about 30 years. The criminal acts commited by 29 (5.7%) of these subjects were so severe that they led to imprisonment. Criminality was not found in the subjects with fronto-temporal injuries more often than in those with injuries to the other areas. Subjects with injuries to the dominant hemisphere appeared to have more criminality than subjects with injuries to the non-dominant hemisphere. The criminal acts were often very accidental and had happened only after several decades following the head injury.", "contents": "Effect of brain injury on social adaptability. Longitudinal study on frequency of criminality. The study tried to clarify social adaptability of persons with brain injuries by using a long-term criminal development as a criterion. Randomly chosen 507 subjects whose open injury originated from the Second World War were followed up for about 30 years. The criminal acts commited by 29 (5.7%) of these subjects were so severe that they led to imprisonment. Criminality was not found in the subjects with fronto-temporal injuries more often than in those with injuries to the other areas. Subjects with injuries to the dominant hemisphere appeared to have more criminality than subjects with injuries to the non-dominant hemisphere. The criminal acts were often very accidental and had happened only after several decades following the head injury."} {"id": "PMID:1274642", "title": "Phylogenetic adaptations and the genetics of psychosis.", "content": "There is evidence that many social skills and responses which are of adaptive value are under a significant degree of genetic control. It is suggested that in states of hyper-arousal these skills are displayed in inappropriate and incomplete forms and that such behaviour constitutes psychosis. Genetic variation in these skills, under polygenic control, appears to be a determinant of the adaptiveness of the personality, with individuals at the extremes of the distribution tending to be maladjusted, chronically overaroused, and vulnerable to psychotic breakdown. Since the individual subjects's psychotic symptomatology will relflect the make-up of his genotype, the hypothesis is consistent with observed familial occurence of the different froms of functional psychosis. The hypothesis explains many of the characteristic manifestations of psychosis, including those in symptomatic psychosis, and also the genetic association with personality disorder. Evidence for the hypothesis and some predictions it generates are briefly reviewed.", "contents": "Phylogenetic adaptations and the genetics of psychosis. There is evidence that many social skills and responses which are of adaptive value are under a significant degree of genetic control. It is suggested that in states of hyper-arousal these skills are displayed in inappropriate and incomplete forms and that such behaviour constitutes psychosis. Genetic variation in these skills, under polygenic control, appears to be a determinant of the adaptiveness of the personality, with individuals at the extremes of the distribution tending to be maladjusted, chronically overaroused, and vulnerable to psychotic breakdown. Since the individual subjects's psychotic symptomatology will relflect the make-up of his genotype, the hypothesis is consistent with observed familial occurence of the different froms of functional psychosis. The hypothesis explains many of the characteristic manifestations of psychosis, including those in symptomatic psychosis, and also the genetic association with personality disorder. Evidence for the hypothesis and some predictions it generates are briefly reviewed."} {"id": "PMID:1274643", "title": "A hospital population of schizophrenic patients undergoing change.", "content": "From a census investigation in 1953 at the Aarhus Psychiatric Hospital, 393 schizophrenic patients were selected (Population 53, P53) and compared with 282 schizophrenics from the 1962 census at the hospital (Population 62, P62). Through hospital records and the central psychiatric register in Denmark, the population from 1953 was followed for 18 years, the 1962 population for 9 years. At admission it appeared that few of the patients had ever married. This was patriculary so for the males. The males were also found to belong to a lower social group than would have been the case in a sample from the general Danish population. In 1962 more patients had obtained State Disability Pension before admission than the 1953 population. More than two-thirds of all admitted schizophrenic patients were in psychiatric hospital within 3 months after onset of illness. Around two-thirds were admitted upon the request of relatives. In the investigated period the expenses for medicine per patient had increased eightfold, whereas expenses for food had less than doubled. Only 15% of the schizophrenic patients in the investigated populations were discharged to their homes. Four per cent were discharged to a nursing home; 22% had died. Of the 15% discharged to their homes, about 50% were readmitted for some time at a later period. In 1962, however, many more patients were discharged after less than 2 years of hospital stay than was the case for the 1953 population. The readmission rates increased from 38% in the 1953 population to 62% in the 1962 population.", "contents": "A hospital population of schizophrenic patients undergoing change. From a census investigation in 1953 at the Aarhus Psychiatric Hospital, 393 schizophrenic patients were selected (Population 53, P53) and compared with 282 schizophrenics from the 1962 census at the hospital (Population 62, P62). Through hospital records and the central psychiatric register in Denmark, the population from 1953 was followed for 18 years, the 1962 population for 9 years. At admission it appeared that few of the patients had ever married. This was patriculary so for the males. The males were also found to belong to a lower social group than would have been the case in a sample from the general Danish population. In 1962 more patients had obtained State Disability Pension before admission than the 1953 population. More than two-thirds of all admitted schizophrenic patients were in psychiatric hospital within 3 months after onset of illness. Around two-thirds were admitted upon the request of relatives. In the investigated period the expenses for medicine per patient had increased eightfold, whereas expenses for food had less than doubled. Only 15% of the schizophrenic patients in the investigated populations were discharged to their homes. Four per cent were discharged to a nursing home; 22% had died. Of the 15% discharged to their homes, about 50% were readmitted for some time at a later period. In 1962, however, many more patients were discharged after less than 2 years of hospital stay than was the case for the 1953 population. The readmission rates increased from 38% in the 1953 population to 62% in the 1962 population."} {"id": "PMID:1274644", "title": "Long-term follow-up of schizophrenic patients in Edinburgh.", "content": "This study is a 12-year follow-up of 153 subjects diagnosed as suffering from schizophrenia or paranoid psychoses. They had their key discharge in the years 1959-61 and were first followed-up at 12 months after discharge (Renton et al. ((1963)). Important findings were that outcome was related to mental state on discharge and also to the factor of continued neuroleptic medication. At this second follow-up 12 years later the important issues that have emerged are the differences in outcome between men and women and the apparently high death rate for men. The outcome in term of work, re-admission to hospital and death was much worse for male subjects.", "contents": "Long-term follow-up of schizophrenic patients in Edinburgh. This study is a 12-year follow-up of 153 subjects diagnosed as suffering from schizophrenia or paranoid psychoses. They had their key discharge in the years 1959-61 and were first followed-up at 12 months after discharge (Renton et al. ((1963)). Important findings were that outcome was related to mental state on discharge and also to the factor of continued neuroleptic medication. At this second follow-up 12 years later the important issues that have emerged are the differences in outcome between men and women and the apparently high death rate for men. The outcome in term of work, re-admission to hospital and death was much worse for male subjects."} {"id": "PMID:1274645", "title": "A reliable clinical technique for investigation of the experienced reality and unreality qualities connected with everyday life experiences in psychotic and non-psychotic persons.", "content": "Eight different pairs of positive and negative qualities of experienced reality are defined. It is described in detail how these qualities can be recorded in relation to specified varieties of experience: a)sensory perceptions, b)fantasies, and c)\"thinking of actually existing objects or properties in persons.\" In a study of 15 non-psychotic patients it was found with a very high reliability that the three varieties of experience each had their characteristic constellation of positive and negative values of the eight qualities of reality. It is pointed out that knowledge of such normal constellations is a logical prerequisite for being able to classify other varieties of experience (hallucinations, delusions, and others) as being pathological.", "contents": "A reliable clinical technique for investigation of the experienced reality and unreality qualities connected with everyday life experiences in psychotic and non-psychotic persons. Eight different pairs of positive and negative qualities of experienced reality are defined. It is described in detail how these qualities can be recorded in relation to specified varieties of experience: a)sensory perceptions, b)fantasies, and c)\"thinking of actually existing objects or properties in persons.\" In a study of 15 non-psychotic patients it was found with a very high reliability that the three varieties of experience each had their characteristic constellation of positive and negative values of the eight qualities of reality. It is pointed out that knowledge of such normal constellations is a logical prerequisite for being able to classify other varieties of experience (hallucinations, delusions, and others) as being pathological."} {"id": "PMID:1274646", "title": "The token economy in the National Health Service: possibilities and limitations.", "content": "The effects after 1 year of the introduction of a token economy system into a long-term male psychiatric ward of 45 mainly schizophrenic patients are described. The main objectives were (1) to define the limits of such programmes in \"average\" National Health Service conditions, where additional resources in staff, finance, and facilities are very limited and (2) to introduce the principles and techniques of behaviour modification to nursing staff. The programme succeeded in reducing social withdrawal and apathy and in increasing self-care skills and involvement in constructive activity. There was no change in the level of socially embarrassing behaviour. The major limitation affecting the maintenance of the programme was found to be the rapid turnover and unpredictable changes in nursing staff. It was concluded that such programmes are feasible with very little in the way of increased resources, and that such efforts will continue to be necessary in view of the existing large numbers of long-tern patients and the slow but significant accumulation of new patients.", "contents": "The token economy in the National Health Service: possibilities and limitations. The effects after 1 year of the introduction of a token economy system into a long-term male psychiatric ward of 45 mainly schizophrenic patients are described. The main objectives were (1) to define the limits of such programmes in \"average\" National Health Service conditions, where additional resources in staff, finance, and facilities are very limited and (2) to introduce the principles and techniques of behaviour modification to nursing staff. The programme succeeded in reducing social withdrawal and apathy and in increasing self-care skills and involvement in constructive activity. There was no change in the level of socially embarrassing behaviour. The major limitation affecting the maintenance of the programme was found to be the rapid turnover and unpredictable changes in nursing staff. It was concluded that such programmes are feasible with very little in the way of increased resources, and that such efforts will continue to be necessary in view of the existing large numbers of long-tern patients and the slow but significant accumulation of new patients."} {"id": "PMID:1274647", "title": "Dimensions of adolescent in-patient behaviour.", "content": "140 adolescent in-patients were rated on a 40-item, 3-point behaviour scale. A principal component analysis was made and two major factors emerged which accounted for 44.3% of the total variance: one factor related to level of functioning and overinhibition and the other to aggression. A graphical representation of the patients with respect to the above factors provided important information as regards prognosis and clinical diagnosis. As in previous related studies (Klein & Davis (1969)), the validity of clinical diagnostic categories was confirmed and information on the process of making these diagnoses was provided.", "contents": "Dimensions of adolescent in-patient behaviour. 140 adolescent in-patients were rated on a 40-item, 3-point behaviour scale. A principal component analysis was made and two major factors emerged which accounted for 44.3% of the total variance: one factor related to level of functioning and overinhibition and the other to aggression. A graphical representation of the patients with respect to the above factors provided important information as regards prognosis and clinical diagnosis. As in previous related studies (Klein & Davis (1969)), the validity of clinical diagnostic categories was confirmed and information on the process of making these diagnoses was provided."} {"id": "PMID:1274648", "title": "Frequency of mental disorders in old age. Examples of comparability of epidemiological investigations in relation to utility in planning.", "content": "Due to the increase in the number of old people, diseases of old age have acquired more and more importance. In estimating the need for psychiatric hospitals and nursing homes, epidemiological investigations are necessary. Only relatively few population investigations of the old-age population have been carried out, and most of these have been carried out in countries in Northern Europe, which are closely related culturally and socially. In the present paper nine investigations are described in relation to certain central factors which include the purpose of the investigation, description of the population, selection of probands, and statistical concepts used, the collection of data, and the main results. Seven of the investigations give results in the form of prevalence, two investigations calculate incidence and morbidity risk. It is concluded that comparison of the various results is difficult as most of the authors have not intended their investigations for mutual comparison. It is clear that there are many dissimilarities in the milieus involved, in the methods used, in the prerequisites of the interviewers and assessors, and in the classification of the results. The investigations presented have been used for evaluation of prognosis and planning of care for the old-age population. It must be said that an investigation is an expression of local truth and as such often usable in local planning, but on the other hand it is not often possible to utilize results from investigations carried out in outside regions for more than a rough basis for local prognosis and local planning. It must therefore be stressed that in future investigations more standardized methods and better correlated descriptions are necessary.", "contents": "Frequency of mental disorders in old age. Examples of comparability of epidemiological investigations in relation to utility in planning. Due to the increase in the number of old people, diseases of old age have acquired more and more importance. In estimating the need for psychiatric hospitals and nursing homes, epidemiological investigations are necessary. Only relatively few population investigations of the old-age population have been carried out, and most of these have been carried out in countries in Northern Europe, which are closely related culturally and socially. In the present paper nine investigations are described in relation to certain central factors which include the purpose of the investigation, description of the population, selection of probands, and statistical concepts used, the collection of data, and the main results. Seven of the investigations give results in the form of prevalence, two investigations calculate incidence and morbidity risk. It is concluded that comparison of the various results is difficult as most of the authors have not intended their investigations for mutual comparison. It is clear that there are many dissimilarities in the milieus involved, in the methods used, in the prerequisites of the interviewers and assessors, and in the classification of the results. The investigations presented have been used for evaluation of prognosis and planning of care for the old-age population. It must be said that an investigation is an expression of local truth and as such often usable in local planning, but on the other hand it is not often possible to utilize results from investigations carried out in outside regions for more than a rough basis for local prognosis and local planning. It must therefore be stressed that in future investigations more standardized methods and better correlated descriptions are necessary."} {"id": "PMID:1274649", "title": "The duration of maintenance therapy in chronic schizophrenia.", "content": "The incidence of relapse was compared between two groups of chronic schizophrenic patients (mean duration periods 19 months and 29.5 months) discontinuing depot neuroleptic injections, and matched controls remaining on depot injections. The results show a higher relapse rate in patients discontinuing injections, significant at the 1% level, in both groups. The proportion of patients improving upon resumption of depot injections confirms the importance of this form of medication in comparison to prescribed oral medication. The results strongly suggest that there is a significant therapeutic gain in continuing maintenance therapy with depot neuroleptic injections for a minimum period of 3 years after the last relapse in a substantial proportion of chronic schizophrenic patients.", "contents": "The duration of maintenance therapy in chronic schizophrenia. The incidence of relapse was compared between two groups of chronic schizophrenic patients (mean duration periods 19 months and 29.5 months) discontinuing depot neuroleptic injections, and matched controls remaining on depot injections. The results show a higher relapse rate in patients discontinuing injections, significant at the 1% level, in both groups. The proportion of patients improving upon resumption of depot injections confirms the importance of this form of medication in comparison to prescribed oral medication. The results strongly suggest that there is a significant therapeutic gain in continuing maintenance therapy with depot neuroleptic injections for a minimum period of 3 years after the last relapse in a substantial proportion of chronic schizophrenic patients."} {"id": "PMID:1274650", "title": "Exploratory behavior in patients suffering from senile dementia: a comparison with children.", "content": "Thirty-seven patients with the diagnosis of senile dementia and 70 children aged 6 months to 4 years were observed in three tasks that stimulated exploratory behavior. The subjects were rated according to the frequencies of certain forms of behavior in 52 variables. It was assumed that certain behavior would be more frequent among children in specific age periods and for that reason a factor analysis of the children's behavior would generate factors characterizing clusters of behavior typical for certain periods. The factor analyses of the children's behavior yielded three factors, which were interpreted as an oral factor, a factor characterizing interest in three-dimensional relationships, and a factor regarding goal-directed manipulation. Indices of the three factors demonstrated that the oral factor had a very high frequency in the infants 6-11 months old; after that age it decreased steeply and disappeared at about 2 years of age. Activities involving three-dimensional relationships and goal-directed manipulation were scarcely displayed in the youngest infants but appeared at about 12 months. Both modes of exploratory behavior tended to disappear before the age of 4. Analyses were carried out to see if the behavior of the patients yielded similar factors, and to see if the distributions of the factor indices for the group of patients, when broken down according to the degree of mental deterioration, had forms similar to the distributions for the children in the different age groups. Similar factors were obtained for the patients, but the structures were less clear and less meaningful than those obtained for the children. The forms of the distributions of factor indices over the degree of mental deterioration were similar to the distributions over the age groups for the children. Motor activity was reduced among more deteriorated patients. When explaining the childlike strategies in the exploratory behavior of the demented patients, it was hypothesized that, due to deficient memory, the patients had to manipulate the objects to find their qualities. This exploratory behavior was more or less advanced and flexible depending on the degree of mental deterioration. However, possible negative effects of high anxiety and high social inhibition were also touched upon.", "contents": "Exploratory behavior in patients suffering from senile dementia: a comparison with children. Thirty-seven patients with the diagnosis of senile dementia and 70 children aged 6 months to 4 years were observed in three tasks that stimulated exploratory behavior. The subjects were rated according to the frequencies of certain forms of behavior in 52 variables. It was assumed that certain behavior would be more frequent among children in specific age periods and for that reason a factor analysis of the children's behavior would generate factors characterizing clusters of behavior typical for certain periods. The factor analyses of the children's behavior yielded three factors, which were interpreted as an oral factor, a factor characterizing interest in three-dimensional relationships, and a factor regarding goal-directed manipulation. Indices of the three factors demonstrated that the oral factor had a very high frequency in the infants 6-11 months old; after that age it decreased steeply and disappeared at about 2 years of age. Activities involving three-dimensional relationships and goal-directed manipulation were scarcely displayed in the youngest infants but appeared at about 12 months. Both modes of exploratory behavior tended to disappear before the age of 4. Analyses were carried out to see if the behavior of the patients yielded similar factors, and to see if the distributions of the factor indices for the group of patients, when broken down according to the degree of mental deterioration, had forms similar to the distributions for the children in the different age groups. Similar factors were obtained for the patients, but the structures were less clear and less meaningful than those obtained for the children. The forms of the distributions of factor indices over the degree of mental deterioration were similar to the distributions over the age groups for the children. Motor activity was reduced among more deteriorated patients. When explaining the childlike strategies in the exploratory behavior of the demented patients, it was hypothesized that, due to deficient memory, the patients had to manipulate the objects to find their qualities. This exploratory behavior was more or less advanced and flexible depending on the degree of mental deterioration. However, possible negative effects of high anxiety and high social inhibition were also touched upon."} {"id": "PMID:1274651", "title": "Objective symmetry detector method for gammaencephalography. V. Variation in the subjective analysis of brain scintigrams.", "content": "The variation caused by the subjective interpretation of brain scintigrams was evaluated and found considerable. It was concluded that the objective analysis of results offered by the objective symmetry detector method for gammaencephalography is advantageous, especially in the screening of large patient materials with a low incidence of brain lesion cases.", "contents": "Objective symmetry detector method for gammaencephalography. V. Variation in the subjective analysis of brain scintigrams. The variation caused by the subjective interpretation of brain scintigrams was evaluated and found considerable. It was concluded that the objective analysis of results offered by the objective symmetry detector method for gammaencephalography is advantageous, especially in the screening of large patient materials with a low incidence of brain lesion cases."} {"id": "PMID:1274652", "title": "Adverse effects of lumbar myelography with amipaque and dimer-X.", "content": "The adverse effects in a series of 50 lumbar myelographies with Amipaque were compared with those in a corresponding series, examined with Dimer-X. Side effects occurred in 58% of the cases examined with Amipaque and in 68% of the Dimer-X series. No seizures occurred in 58% of the cases examined with Amipaque and in 68% of the Dimer-X series. No seizures occurred in either series but slight fibrillations of fasciculations appeared in 2 Dimer-X patients. Hyperreflexia of the legs was recorded in 22% of the Amipaque and in 36% of the Dimer-X cases. Other adverse reactions to the media were mild to moderate. Some burst activity, but no definite paroxysmal abnormality was noted in EEG recordings in 2 Amipaque cases. The low epileptogenicity of Amipaque has ensured a wider safety margin of lumbar myelography.", "contents": "Adverse effects of lumbar myelography with amipaque and dimer-X. The adverse effects in a series of 50 lumbar myelographies with Amipaque were compared with those in a corresponding series, examined with Dimer-X. Side effects occurred in 58% of the cases examined with Amipaque and in 68% of the Dimer-X series. No seizures occurred in 58% of the cases examined with Amipaque and in 68% of the Dimer-X series. No seizures occurred in either series but slight fibrillations of fasciculations appeared in 2 Dimer-X patients. Hyperreflexia of the legs was recorded in 22% of the Amipaque and in 36% of the Dimer-X cases. Other adverse reactions to the media were mild to moderate. Some burst activity, but no definite paroxysmal abnormality was noted in EEG recordings in 2 Amipaque cases. The low epileptogenicity of Amipaque has ensured a wider safety margin of lumbar myelography."} {"id": "PMID:1274653", "title": "Persistent hypoglossal artery, diagnostic criteria. Report of a case.", "content": "After a brief racapitulation of the embryology of the vertebrobasilar arterial system, one new case (the 26th) with a persistent hypoglossal artery is presented. As in this case a well developed posterior communicating artery existed, new diagnostic criteria have been formulated.", "contents": "Persistent hypoglossal artery, diagnostic criteria. Report of a case. After a brief racapitulation of the embryology of the vertebrobasilar arterial system, one new case (the 26th) with a persistent hypoglossal artery is presented. As in this case a well developed posterior communicating artery existed, new diagnostic criteria have been formulated."} {"id": "PMID:1274654", "title": "Spinal cord vascularity. II. Extraspinal sources of spinal cord arteries in the rat.", "content": "The arrangement of extravertebral sources of spinal cord arteries in the rat is similar to that in man. Some differences, however, do exist, concerning mainly the arrangement of spinal branches supplied by the subclavian-vertebral arteries. Contrary to the situation in man, the vertebral artery in the rat appears to be the sole source of blood supply to the cervical cord. A high incidence of variations or anomalies of the vertebral artery in the rat existed. Vascular variations in the upper left thoracic spaces were frequent in the rat and more complicated than in man. In both species, a poor supply of significant spinal cord feeders from the superior intercostal artery of the costocervical trunk was found. Variations in the origin and branching of the aortic segmental arteries occur in both species. In man the major variation consists of two or more intercostal arteries arising from a common stem, while the rat more often displays a rudimentary subcostal artery. Finally, the ileolumbar arteries in the rat are constant branches of the lumbar aorta. Despite these differences in the vascular anatomy, the rat seems to be well suited for experimental comparative investigations, not feasible in man.", "contents": "Spinal cord vascularity. II. Extraspinal sources of spinal cord arteries in the rat. The arrangement of extravertebral sources of spinal cord arteries in the rat is similar to that in man. Some differences, however, do exist, concerning mainly the arrangement of spinal branches supplied by the subclavian-vertebral arteries. Contrary to the situation in man, the vertebral artery in the rat appears to be the sole source of blood supply to the cervical cord. A high incidence of variations or anomalies of the vertebral artery in the rat existed. Vascular variations in the upper left thoracic spaces were frequent in the rat and more complicated than in man. In both species, a poor supply of significant spinal cord feeders from the superior intercostal artery of the costocervical trunk was found. Variations in the origin and branching of the aortic segmental arteries occur in both species. In man the major variation consists of two or more intercostal arteries arising from a common stem, while the rat more often displays a rudimentary subcostal artery. Finally, the ileolumbar arteries in the rat are constant branches of the lumbar aorta. Despite these differences in the vascular anatomy, the rat seems to be well suited for experimental comparative investigations, not feasible in man."} {"id": "PMID:1274655", "title": "Spontaneous carotid-cavernous fistulas: phlebographic appearance and relation to thrombosis.", "content": "Six consecutive cases with spontaneous carotid-cavernous fistulas were examined with orbital phlebography and bilateral carotid angiography. One of the fistulas was fed only by one internal carotid artery, 1 only by the accessory meningeal branch of the maxillary artery, while 4 were supplied by external as well as internal carotid arteries. The findings at phlebography seem to be characteristic. Thrombosis was demonstrated in all 6 cases. Different mechanisms for the genesis of thrombosis in association with carotid-cavernous fistulas are proposed. Alternative therapy methods are discussed.", "contents": "Spontaneous carotid-cavernous fistulas: phlebographic appearance and relation to thrombosis. Six consecutive cases with spontaneous carotid-cavernous fistulas were examined with orbital phlebography and bilateral carotid angiography. One of the fistulas was fed only by one internal carotid artery, 1 only by the accessory meningeal branch of the maxillary artery, while 4 were supplied by external as well as internal carotid arteries. The findings at phlebography seem to be characteristic. Thrombosis was demonstrated in all 6 cases. Different mechanisms for the genesis of thrombosis in association with carotid-cavernous fistulas are proposed. Alternative therapy methods are discussed."} {"id": "PMID:1274656", "title": "Radiology for detecting brain tumor recurrences.", "content": "Angiography, 99Tcm-pertechnetate scintigraphy and encephalography are compared in their efficacy in the detection of tumor recurrences in 45 patients following brain tumor resection. No single method is always preferable and the best way of detecting a particular tumor recurrence is based on the location and nature of the primary tumor. Scintigraphy is the method of choice for performing routine postoperative follow-up. In cerebral hemisphere tumors angiography may be replaced by brain scanning which is a lesser procedure for the patient and does not necessitate hospitalisation. Encephalography is the examination favoured for detecting recurrences near the base of the skull. Angiography is the best method for demonstrating recurrences near the surface in the region of craniotomy and is essential before reoperation.", "contents": "Radiology for detecting brain tumor recurrences. Angiography, 99Tcm-pertechnetate scintigraphy and encephalography are compared in their efficacy in the detection of tumor recurrences in 45 patients following brain tumor resection. No single method is always preferable and the best way of detecting a particular tumor recurrence is based on the location and nature of the primary tumor. Scintigraphy is the method of choice for performing routine postoperative follow-up. In cerebral hemisphere tumors angiography may be replaced by brain scanning which is a lesser procedure for the patient and does not necessitate hospitalisation. Encephalography is the examination favoured for detecting recurrences near the base of the skull. Angiography is the best method for demonstrating recurrences near the surface in the region of craniotomy and is essential before reoperation."} {"id": "PMID:1274657", "title": "Vascular complications following needle puncture of the liver. Clinical angiography.", "content": "Angiography after liver puncture was performed at different intervals in 51 patients. Fourteen cases had abnormalities believed to be caused by the puncture. Most of these were small but there were also 4 cases with large liver hematomas and 1 case with an abscess between the liver and the abdominal wall, none requiring acute surgery. No certain correlation between the severity of the injury and the diameter of the puncture instrument could be assessed.", "contents": "Vascular complications following needle puncture of the liver. Clinical angiography. Angiography after liver puncture was performed at different intervals in 51 patients. Fourteen cases had abnormalities believed to be caused by the puncture. Most of these were small but there were also 4 cases with large liver hematomas and 1 case with an abscess between the liver and the abdominal wall, none requiring acute surgery. No certain correlation between the severity of the injury and the diameter of the puncture instrument could be assessed."} {"id": "PMID:1274658", "title": "Radiographic measurements of the radio-carpal joint in normal adults.", "content": "Radiography of 60 normal wrists was performed in 50 adults to determine the inclination of the distal joint surface of the radius. The central ray was directed 10 degrees proximally in postero-anterior projection and 15 degree proximally in lateral projection. The values obtained were compared with those from perpendicular projections. No dfferences were found between the two p.a. projections. In the lateral projection with the central ray directed proximally the measuring points were better defined, resulting in significantly increased exactness of the measurement. The mean value for the volar inclination was 9 degrees in the latter projection.", "contents": "Radiographic measurements of the radio-carpal joint in normal adults. Radiography of 60 normal wrists was performed in 50 adults to determine the inclination of the distal joint surface of the radius. The central ray was directed 10 degrees proximally in postero-anterior projection and 15 degree proximally in lateral projection. The values obtained were compared with those from perpendicular projections. No dfferences were found between the two p.a. projections. In the lateral projection with the central ray directed proximally the measuring points were better defined, resulting in significantly increased exactness of the measurement. The mean value for the volar inclination was 9 degrees in the latter projection."} {"id": "PMID:1274659", "title": "Prognostic factors in mammary carcinoma.", "content": "The simultaneous prognostic influence of multiple clinical and microscopic features of mammary carcinoma was analysed in 581 women with radical mastectomy. The most important of these features were connected with the extent of the disease in the axillary lymph nodes. In substantial groups of patients, however, a favourable outcome could be predicted from microscopic features of the primary tumour, viz. tubule formation, mitotic frequency and elastosis.", "contents": "Prognostic factors in mammary carcinoma. The simultaneous prognostic influence of multiple clinical and microscopic features of mammary carcinoma was analysed in 581 women with radical mastectomy. The most important of these features were connected with the extent of the disease in the axillary lymph nodes. In substantial groups of patients, however, a favourable outcome could be predicted from microscopic features of the primary tumour, viz. tubule formation, mitotic frequency and elastosis."} {"id": "PMID:1274660", "title": "Results of irradiation of tumors in the region of the pineal body.", "content": "The clinical findings and results of radiation treatment in 14 patients with tumors in the region of the pineal body are presented. The neurologic signs and symptoms improved significantly in 11 patients (79 per cent). The survival rate for five years or more was 50 per cent. Radiation therapy as the primary method of treatment is discussed.", "contents": "Results of irradiation of tumors in the region of the pineal body. The clinical findings and results of radiation treatment in 14 patients with tumors in the region of the pineal body are presented. The neurologic signs and symptoms improved significantly in 11 patients (79 per cent). The survival rate for five years or more was 50 per cent. Radiation therapy as the primary method of treatment is discussed."} {"id": "PMID:1274661", "title": "DNA-synthesis of lymphocytes in hyperthyroid and euthyroid subjects. Effect of 131I therapy on hyperthyroidism.", "content": "The DNA-synthesis of human lymphoid cells as estimated by the measurement of thymidine incorporation in vitro was investigated in healthy controls and in patients with various thyroid disorders before and after therapy. Hyperthyroid patients treated with 131I and surgery (euthyroid at initial blood sampling before surgery), patients with atoxic nodular goitre treated by surgery and healthy untreated control individuals comprised the material. The synthesis of DNA in lymphocytes was higher in hyperthyroid patients in comparison with euthyroid individuals, and decreased subsequent to 131I therapy in the hyperthyroid patients. No decrease was recorded in the other groups of patients. No evidence suggesting a change in the lymphocyte reactivity to thyroglobulin was found in any of the patient groups.", "contents": "DNA-synthesis of lymphocytes in hyperthyroid and euthyroid subjects. Effect of 131I therapy on hyperthyroidism. The DNA-synthesis of human lymphoid cells as estimated by the measurement of thymidine incorporation in vitro was investigated in healthy controls and in patients with various thyroid disorders before and after therapy. Hyperthyroid patients treated with 131I and surgery (euthyroid at initial blood sampling before surgery), patients with atoxic nodular goitre treated by surgery and healthy untreated control individuals comprised the material. The synthesis of DNA in lymphocytes was higher in hyperthyroid patients in comparison with euthyroid individuals, and decreased subsequent to 131I therapy in the hyperthyroid patients. No decrease was recorded in the other groups of patients. No evidence suggesting a change in the lymphocyte reactivity to thyroglobulin was found in any of the patient groups."} {"id": "PMID:1274662", "title": "A preliminary experiment on regression of human ovarian tumor transplants in athymic nude mice following a single exposure to 60Co radiation.", "content": "Human ovarian tumour transplants (AN-LE) are grown in the thymus defective nude mouse mutant (nu/nu BALB/c/A/Bom). Procedures for local irradiation of the tumors with 60Co-radiation are described. An introductory test of the usefulness of these transplants in studies of radiation effects on human tumors is performed by investigation of the time course of regression of AN-LE transplants in 6 mice, following single exposures to 375, 750 1 180, and 1 575 rad, respectively.", "contents": "A preliminary experiment on regression of human ovarian tumor transplants in athymic nude mice following a single exposure to 60Co radiation. Human ovarian tumour transplants (AN-LE) are grown in the thymus defective nude mouse mutant (nu/nu BALB/c/A/Bom). Procedures for local irradiation of the tumors with 60Co-radiation are described. An introductory test of the usefulness of these transplants in studies of radiation effects on human tumors is performed by investigation of the time course of regression of AN-LE transplants in 6 mice, following single exposures to 375, 750 1 180, and 1 575 rad, respectively."} {"id": "PMID:1274663", "title": "Influence of diagnostic roentgen doses on human chromosomes and influence of age on the aberration yield.", "content": "Urography was performed in 2 groups of patients (one comprising patients aged 7-18 years, the other patients aged 8-32 months) under constant conditions. The skin dose ranged between 1 and 4 R. Blood samples were taken before, immediately after and 24 hours after the irradiation. A significantly increased number of aberrant cells was found only in the blood samples taken 24 hours after irradiation. No age-dependent influence on the radiation sensitivity in vivo was found.", "contents": "Influence of diagnostic roentgen doses on human chromosomes and influence of age on the aberration yield. Urography was performed in 2 groups of patients (one comprising patients aged 7-18 years, the other patients aged 8-32 months) under constant conditions. The skin dose ranged between 1 and 4 R. Blood samples were taken before, immediately after and 24 hours after the irradiation. A significantly increased number of aberrant cells was found only in the blood samples taken 24 hours after irradiation. No age-dependent influence on the radiation sensitivity in vivo was found."} {"id": "PMID:1274671", "title": "Liver biopsies in epileptics during anticonvulsant therapy.", "content": "Liver function tests, performed in 11 epileptics under antiepileptic treatment for 10-35 years, showed a slight increase in serum alanine amino-transferase in six patients and a marked increased level of serum alkaline phosphatases in four. Liver biopsies revealed few uni- or paucicellular necroses in five patients. Granulomatous hepatitis was found in one patient in whom sarcoidosis was later diagnosed. None of the biopsies showed signs of permanent liver damage.", "contents": "Liver biopsies in epileptics during anticonvulsant therapy. Liver function tests, performed in 11 epileptics under antiepileptic treatment for 10-35 years, showed a slight increase in serum alanine amino-transferase in six patients and a marked increased level of serum alkaline phosphatases in four. Liver biopsies revealed few uni- or paucicellular necroses in five patients. Granulomatous hepatitis was found in one patient in whom sarcoidosis was later diagnosed. None of the biopsies showed signs of permanent liver damage."} {"id": "PMID:1274672", "title": "Anticonvulsant osteomalacia determined by quantitative analysis of bone changes. Population study and possible risk factors.", "content": "Material has been obtained by biopsy from the right iliac crest of 60 adult epileptic out-patients receiving chronic anticonvulsant therapy with diphenylhydantoin (DPH), either in single-drug or combined-drug regime, and of 16 controls with the same distribution by sex and age. Four (7%) of the epileptics were hypocalcemic and 25 (42%) had elevated serum alkaline phosphatase values. A quantitative analysis of the morphological bone changes was performed on decalcified and undecalcified bone, using integrating filters and the point count principle. An increased amount of unmineralized bone was found in 32 (53%) of the epileptics. The trabecular osteoclastic resorption surfaces and the mean volume of periosteocytic lacunae were increased in 36 (69%) and 45 (75%) patients, respectively. The calcification rate was decreased in relation to what is referred to elsewhere as normal. The bone changes suggest a mineralization defect analogous to osetomalacia with secondary hyperparathyroidism. An increased osteoid volume or thickness and decreased calcification rate were correlated to low dietary vitamin D intake, low exposure to sunlight, high hepatic clearance rate of DPH, combined-drug treatment and the male sex. These parameters should be considered risk factors of anticonvulsant osteomalacia.", "contents": "Anticonvulsant osteomalacia determined by quantitative analysis of bone changes. Population study and possible risk factors. Material has been obtained by biopsy from the right iliac crest of 60 adult epileptic out-patients receiving chronic anticonvulsant therapy with diphenylhydantoin (DPH), either in single-drug or combined-drug regime, and of 16 controls with the same distribution by sex and age. Four (7%) of the epileptics were hypocalcemic and 25 (42%) had elevated serum alkaline phosphatase values. A quantitative analysis of the morphological bone changes was performed on decalcified and undecalcified bone, using integrating filters and the point count principle. An increased amount of unmineralized bone was found in 32 (53%) of the epileptics. The trabecular osteoclastic resorption surfaces and the mean volume of periosteocytic lacunae were increased in 36 (69%) and 45 (75%) patients, respectively. The calcification rate was decreased in relation to what is referred to elsewhere as normal. The bone changes suggest a mineralization defect analogous to osetomalacia with secondary hyperparathyroidism. An increased osteoid volume or thickness and decreased calcification rate were correlated to low dietary vitamin D intake, low exposure to sunlight, high hepatic clearance rate of DPH, combined-drug treatment and the male sex. These parameters should be considered risk factors of anticonvulsant osteomalacia."} {"id": "PMID:1274673", "title": "Serum lipids in alcoholics.", "content": "Fasting serum lipid values (cholesterol, triglycerides and phospholipids) have been analysed in a group of 85 male and 10 female alcoholics of various ages in connection with an acute drinking bout and compared to the values of twice as many control subjects. The most prominent finding was an increase in the mean concentration of triglycerides and phospholipids, most marked in the younger age groups. The elevations, however, were moderate and most alcoholics had the same serum lipid values as the controls. Serum triglyceride values above 2 and 3 mmol/1, respectively, occurred in 23% and 4% in controls and in 28% and 13% in alcoholics. It is suggested that excessive intake of alcohol induces hypertriglyceridaemia only when other factors are present. One such factor may be a reduced i.v. fat tolerance.", "contents": "Serum lipids in alcoholics. Fasting serum lipid values (cholesterol, triglycerides and phospholipids) have been analysed in a group of 85 male and 10 female alcoholics of various ages in connection with an acute drinking bout and compared to the values of twice as many control subjects. The most prominent finding was an increase in the mean concentration of triglycerides and phospholipids, most marked in the younger age groups. The elevations, however, were moderate and most alcoholics had the same serum lipid values as the controls. Serum triglyceride values above 2 and 3 mmol/1, respectively, occurred in 23% and 4% in controls and in 28% and 13% in alcoholics. It is suggested that excessive intake of alcohol induces hypertriglyceridaemia only when other factors are present. One such factor may be a reduced i.v. fat tolerance."} {"id": "PMID:1274674", "title": "Ventricular fibrillation after intravenous atropine for treatment of sinus bradycardia.", "content": "A patient with acute myocardial infarction and sinus bradycardia has been treated with 0.5 mg atropine intravenously. Shortly after the injection he showed a sinus tachycardia, then developed ventricular ectopic beats, ventricular tachycardia and ventricular fibrillation, which was treated successfully with electrical countershock.", "contents": "Ventricular fibrillation after intravenous atropine for treatment of sinus bradycardia. A patient with acute myocardial infarction and sinus bradycardia has been treated with 0.5 mg atropine intravenously. Shortly after the injection he showed a sinus tachycardia, then developed ventricular ectopic beats, ventricular tachycardia and ventricular fibrillation, which was treated successfully with electrical countershock."} {"id": "PMID:1274676", "title": "Resumption of work after acute myocardial infarction.", "content": "A total of 644 patients, admitted to the Coronary Care Unit of a district hospital on account of acute myocardial infarction, have been discharged during a 3-year period. Of these patients, 71% had been employed at the time of the infarction and more than 80% of this group returned to work. Among the long-term survivors (LTS) aged less than 65 years who had been employed at the time of infarction, 87% of the male and 74% of the female patients had resumed work some time afterwards. Among 347 LTS age was found to be the main factor to determine whether or not patients would be able to resume work, whereas the number of experienced infarctions as well as signs and/or symptoms of heart failure during the acute phase were of no consequence. The occurrence of additional symptoms of ischaemic heart diseases (recurrences of infarction, presence of angina pectoris, demand for drugs) was of prognostic importance for whether or not patients would have to abandon work. The ability of patients to resume their previous work. The ability of patients to resume their previous work depended on the character of the latter, i.e. its type and the physical strain involved. About 80% of the LTS resumed work within three months. Patients in whom heart failure had occurred during the acute phase tended to return to work later than those without this complication. No more than half of the LTS who had abandoned work declared that cardiac symptoms had been the reason.", "contents": "Resumption of work after acute myocardial infarction. A total of 644 patients, admitted to the Coronary Care Unit of a district hospital on account of acute myocardial infarction, have been discharged during a 3-year period. Of these patients, 71% had been employed at the time of the infarction and more than 80% of this group returned to work. Among the long-term survivors (LTS) aged less than 65 years who had been employed at the time of infarction, 87% of the male and 74% of the female patients had resumed work some time afterwards. Among 347 LTS age was found to be the main factor to determine whether or not patients would be able to resume work, whereas the number of experienced infarctions as well as signs and/or symptoms of heart failure during the acute phase were of no consequence. The occurrence of additional symptoms of ischaemic heart diseases (recurrences of infarction, presence of angina pectoris, demand for drugs) was of prognostic importance for whether or not patients would have to abandon work. The ability of patients to resume their previous work. The ability of patients to resume their previous work depended on the character of the latter, i.e. its type and the physical strain involved. About 80% of the LTS resumed work within three months. Patients in whom heart failure had occurred during the acute phase tended to return to work later than those without this complication. No more than half of the LTS who had abandoned work declared that cardiac symptoms had been the reason."} {"id": "PMID:1274677", "title": "Characteristics of representative male survivors of myocardial infarction compared with representative population samples.", "content": "A series of 299 men, aged 27-67, who had survived their first myocardial infarction (MI), have been compared with representative population samples with respect to tobacco consumption, alcoholic intemperance, physical activity during work and leisure time, occurrence of hypertension, and cholesterol and triglyceride levels in serum. The infarction patients comprised 90% of all surviving, diagnosed cases of primary MI in men aged 67 years or below during 1968-70 in G\u00f6teborg, Sweden. The comparison between infarction patients and general population samples revealed that the patients smoked more, and were less physically active during leisure time but not during work. They had more often a positive history of hypertension and treatment for high BP and their serum cholesterol and serum triglyceride values were higher. For all these variables the difference decreased with increasing age and was generally not statistically significant above the age of 60 years. Alcoholic intemperance was more common among infarction patients who died outside hospital, but there was no difference in this respect between surviving patients and the general population.", "contents": "Characteristics of representative male survivors of myocardial infarction compared with representative population samples. A series of 299 men, aged 27-67, who had survived their first myocardial infarction (MI), have been compared with representative population samples with respect to tobacco consumption, alcoholic intemperance, physical activity during work and leisure time, occurrence of hypertension, and cholesterol and triglyceride levels in serum. The infarction patients comprised 90% of all surviving, diagnosed cases of primary MI in men aged 67 years or below during 1968-70 in G\u00f6teborg, Sweden. The comparison between infarction patients and general population samples revealed that the patients smoked more, and were less physically active during leisure time but not during work. They had more often a positive history of hypertension and treatment for high BP and their serum cholesterol and serum triglyceride values were higher. For all these variables the difference decreased with increasing age and was generally not statistically significant above the age of 60 years. Alcoholic intemperance was more common among infarction patients who died outside hospital, but there was no difference in this respect between surviving patients and the general population."} {"id": "PMID:1274678", "title": "Systemic lupus erythematosus in twin sisters following ten years of hyperglobulinemic purpura (Waldenstr\u00f6m).", "content": "Uniovular twin sisters have been diagnosed 10 years ago as having hyperglobulinemic purpura (Waldenstr\u00f6m) at age 12. The diagnosis was documented by purpura of the lower extremities, increased gamma-globulin after serum electrophoresis, and increased 7S component upon ultracentrifugation. In addition, there was an elevated ESR, a positive rheumatoid arthritis latex test, and their LE prep. was negative at that time. At a later date, however, both of them developed polyarthritis. After 9 years for the one and 10 years for the other, their LE prep. became strongly and constantly positive, while their gamma-globulin remained within abnormal limits.", "contents": "Systemic lupus erythematosus in twin sisters following ten years of hyperglobulinemic purpura (Waldenstr\u00f6m). Uniovular twin sisters have been diagnosed 10 years ago as having hyperglobulinemic purpura (Waldenstr\u00f6m) at age 12. The diagnosis was documented by purpura of the lower extremities, increased gamma-globulin after serum electrophoresis, and increased 7S component upon ultracentrifugation. In addition, there was an elevated ESR, a positive rheumatoid arthritis latex test, and their LE prep. was negative at that time. At a later date, however, both of them developed polyarthritis. After 9 years for the one and 10 years for the other, their LE prep. became strongly and constantly positive, while their gamma-globulin remained within abnormal limits."} {"id": "PMID:1274679", "title": "Morphological aspects and biomechanical properties of the vertebroaxial joint (C2-C3).", "content": "The C2-C3 intervertebral joint must be regarded as a transitional area situated between the upper cervical spine where most rotation of the neck and little flexion and extension occur and the lower cervical spaces where chiefly motion in the sagittal plane and also somewhat rotation take place. Under normal circumstances the range of flexion-extension reaches 11 degrees, slighter than below (19.5 degrees at C5-C6); on the opposite, the range of rotation attains 7 degrees; less than above but much more than below (0 degrees at C5-C6). The motion in the sagittal and coronal planes is relatively poor because of the location of Penning's motor-axis of C2 which runs far from the vertebral body and the lowness of the intervertebral disc. However, the rotation of C2 with respect to C3 is fair by the peculiar inclination of the articular facets which slope sagittally but also coronally and trace a sphere whereupon C2 may move around its motor-centre in any plane. When C2-C3 is surgically fixed by bone graft, the lack of motion is completed by a \"compensatory movement\" in the upper cervical spaces and especially at the atlantooccipital joint for flexion-extension. In the same way, C2-C3 may improve its mobility especially in the sagittal plane when the inferior partner is blocked by surgical or arthritic fusion.", "contents": "Morphological aspects and biomechanical properties of the vertebroaxial joint (C2-C3). The C2-C3 intervertebral joint must be regarded as a transitional area situated between the upper cervical spine where most rotation of the neck and little flexion and extension occur and the lower cervical spaces where chiefly motion in the sagittal plane and also somewhat rotation take place. Under normal circumstances the range of flexion-extension reaches 11 degrees, slighter than below (19.5 degrees at C5-C6); on the opposite, the range of rotation attains 7 degrees; less than above but much more than below (0 degrees at C5-C6). The motion in the sagittal and coronal planes is relatively poor because of the location of Penning's motor-axis of C2 which runs far from the vertebral body and the lowness of the intervertebral disc. However, the rotation of C2 with respect to C3 is fair by the peculiar inclination of the articular facets which slope sagittally but also coronally and trace a sphere whereupon C2 may move around its motor-centre in any plane. When C2-C3 is surgically fixed by bone graft, the lack of motion is completed by a \"compensatory movement\" in the upper cervical spaces and especially at the atlantooccipital joint for flexion-extension. In the same way, C2-C3 may improve its mobility especially in the sagittal plane when the inferior partner is blocked by surgical or arthritic fusion."} {"id": "PMID:1274680", "title": "On the acetylcholinesterase activity in the vestibular ganglion of the rat.", "content": "Acetylcholinesterase was demonstrated in the ganglion cells of the vestibular ganglion of the rat with Karnovsky's method. The acetylcholinesterase content was evaluated after a 24 hours incubation time by means of a three-grade scale. The cell size was determined by a particle size analyser. No correlation between the two values could be established. A comparison with the spiral ganglion showed a slightly lower acetylcholinesterase content in the vestibular ganglion. The content of acetylcholinesterase in the vestibular ganglion cells seems to be lower than in the spinal ganglion cells.", "contents": "On the acetylcholinesterase activity in the vestibular ganglion of the rat. Acetylcholinesterase was demonstrated in the ganglion cells of the vestibular ganglion of the rat with Karnovsky's method. The acetylcholinesterase content was evaluated after a 24 hours incubation time by means of a three-grade scale. The cell size was determined by a particle size analyser. No correlation between the two values could be established. A comparison with the spiral ganglion showed a slightly lower acetylcholinesterase content in the vestibular ganglion. The content of acetylcholinesterase in the vestibular ganglion cells seems to be lower than in the spinal ganglion cells."} {"id": "PMID:1274681", "title": "Biology of the rice rat (Oryzomys palustris natator) in a laboratory environment. IX. Preweaning growth of the skull.", "content": "The pattern of skull growth of the rice rat (Oryzomys palustris natator) over the pre-weaning period of development reveals a characteristic triphasic outline which stems, in part, from the interplay of the external environment and the genetic endowment. Within the triphasic spectrum the neural skull growth exhibits an accelerated rate of growth during the early phases which eventually reverses to a rapid deceleration in the final phase. In contrast, the facial skull growth shows increased growth rate following the decline of the neural group, eventually reaching a slow linear deceleration. Thus the neural components appear to be synchronised to the brain growth while the facial elements gain a new and greater impetus following the neural decline. The general growth of the skull throughout these changes, i.e. triphasic and neural/facial, continues to show a basic slow linear increase.", "contents": "Biology of the rice rat (Oryzomys palustris natator) in a laboratory environment. IX. Preweaning growth of the skull. The pattern of skull growth of the rice rat (Oryzomys palustris natator) over the pre-weaning period of development reveals a characteristic triphasic outline which stems, in part, from the interplay of the external environment and the genetic endowment. Within the triphasic spectrum the neural skull growth exhibits an accelerated rate of growth during the early phases which eventually reverses to a rapid deceleration in the final phase. In contrast, the facial skull growth shows increased growth rate following the decline of the neural group, eventually reaching a slow linear deceleration. Thus the neural components appear to be synchronised to the brain growth while the facial elements gain a new and greater impetus following the neural decline. The general growth of the skull throughout these changes, i.e. triphasic and neural/facial, continues to show a basic slow linear increase."} {"id": "PMID:1274682", "title": "The effects of experimental unilateral anotia on skull development in the chick embryo. III. Chondrocranial development in anotic embryos of 7-20 days of incubation.", "content": "The study of the development of of the chondrocranium in chick embryos with unilateral (right-sided) anotia revealed the following main characteristics. 1. The median axes of the chordal and the prechordal part of the cranial base are not in a straight line but show a deviation toward the right side. The angle between the two axes has its vertex in the region of the foramen hypophyseos. 2. The metotic cartilage and the foramina of the IXth and Xth cranial nerves are normal in position. 3. The tectum synoticum develops later and to a lesser extent than normal. 4. Between the basal plate, the metotic cartilage, the occipital arch and the supracapsular cartilage a foramen is formed which, later in development, is closed by outgrowths of the metotic cartilage and the basal plate. 5. The \"optic area\" shows a practically normal appearance which indicates that the cartilaginous ventral wall of the lagenal capsule is of basal plate origin. 6. The pro-otic process develops practically normal and, hence, is independent of the ear capsule. 7. The quadrate cartilage and the right lower jaw are displaced ventro-posteriorward. The earliest development of the perichondral bones shows some particularities which are closely correlated with the development of the various cartilaginous structures.", "contents": "The effects of experimental unilateral anotia on skull development in the chick embryo. III. Chondrocranial development in anotic embryos of 7-20 days of incubation. The study of the development of of the chondrocranium in chick embryos with unilateral (right-sided) anotia revealed the following main characteristics. 1. The median axes of the chordal and the prechordal part of the cranial base are not in a straight line but show a deviation toward the right side. The angle between the two axes has its vertex in the region of the foramen hypophyseos. 2. The metotic cartilage and the foramina of the IXth and Xth cranial nerves are normal in position. 3. The tectum synoticum develops later and to a lesser extent than normal. 4. Between the basal plate, the metotic cartilage, the occipital arch and the supracapsular cartilage a foramen is formed which, later in development, is closed by outgrowths of the metotic cartilage and the basal plate. 5. The \"optic area\" shows a practically normal appearance which indicates that the cartilaginous ventral wall of the lagenal capsule is of basal plate origin. 6. The pro-otic process develops practically normal and, hence, is independent of the ear capsule. 7. The quadrate cartilage and the right lower jaw are displaced ventro-posteriorward. The earliest development of the perichondral bones shows some particularities which are closely correlated with the development of the various cartilaginous structures."} {"id": "PMID:1274699", "title": "Surgical indications in normotensive hydrocephalus. A retrospective analysis of the relations of some diagnostic findings to the results of surgical treatment.", "content": "Twenty two of fifty five patients initially suspected of suffering from normotensive hydrocephalus were surgically treated (CSF ventriculoatrial shunt). The results of surgery were related to the findings of the different diagnostic examinations (pneumoencephalography, isotope cisternography, transfer fron CSF to blood of isotope labelled serum albumin, constant infusion manometric test, long lasting intraventricular pressure recording). 1.Pneumoencephalography, intraventricular pressure recording, and, above all, isotope cisternography provided the most reliable data for diagnosis and surgical prognosis. 2. The combined use of pneumoencephalography and isotope cisternography was sufficient for a correct diagnosis and surgical prognosis in about 50% of the patients examined. 3. When the diagnostic information given by the combined results of the two above examinations was not sufficient, intraventricular pressure recording proved to be the most useful examination to supplement it. 4. The relation of the results of the study of transfer of istope labelled serum albumin from CSF to blood and of the constant infusion manometric test to the surgical outcome was uncertain.", "contents": "Surgical indications in normotensive hydrocephalus. A retrospective analysis of the relations of some diagnostic findings to the results of surgical treatment. Twenty two of fifty five patients initially suspected of suffering from normotensive hydrocephalus were surgically treated (CSF ventriculoatrial shunt). The results of surgery were related to the findings of the different diagnostic examinations (pneumoencephalography, isotope cisternography, transfer fron CSF to blood of isotope labelled serum albumin, constant infusion manometric test, long lasting intraventricular pressure recording). 1.Pneumoencephalography, intraventricular pressure recording, and, above all, isotope cisternography provided the most reliable data for diagnosis and surgical prognosis. 2. The combined use of pneumoencephalography and isotope cisternography was sufficient for a correct diagnosis and surgical prognosis in about 50% of the patients examined. 3. When the diagnostic information given by the combined results of the two above examinations was not sufficient, intraventricular pressure recording proved to be the most useful examination to supplement it. 4. The relation of the results of the study of transfer of istope labelled serum albumin from CSF to blood and of the constant infusion manometric test to the surgical outcome was uncertain."} {"id": "PMID:1274700", "title": "Tabetic lumbar osteoarthropathy with cauda equina syndrome. Case report.", "content": "The case is described of a 52 year old patient admitted for acauda equina compression syndrome (flaccid paraplegia of the lower limbs, bilateral lumbar and sciatic pains, urinary incontinence) of rapid onset and due to narrowing of the lumbar canal from tabetic arthropathy. These vertebral manifestations occur in a low percentage of tabetic arthropathies, which are relatively rare, and are not often accompanied by severe neurological disturbances. Decompressive laminectomy afforded rapid and lasting relief.", "contents": "Tabetic lumbar osteoarthropathy with cauda equina syndrome. Case report. The case is described of a 52 year old patient admitted for acauda equina compression syndrome (flaccid paraplegia of the lower limbs, bilateral lumbar and sciatic pains, urinary incontinence) of rapid onset and due to narrowing of the lumbar canal from tabetic arthropathy. These vertebral manifestations occur in a low percentage of tabetic arthropathies, which are relatively rare, and are not often accompanied by severe neurological disturbances. Decompressive laminectomy afforded rapid and lasting relief."} {"id": "PMID:1274701", "title": "[Epidural hemangiopericytoma. A casuistic contribution to the differential diagnosis of angiomatous meningiomas].", "content": "The clinical presentation together with macroscopic and microscopic findings in a case of epidural fronto-parasagittal hemangiopericytoma occurring in a 59 years old female are reported. Pathogenesis, clinical and macroscopic findings, and microscopicaspects of this tumor aspected with the angioblastic (angiomatous) meningioma are discussed. The relevant literature is reviewed.", "contents": "[Epidural hemangiopericytoma. A casuistic contribution to the differential diagnosis of angiomatous meningiomas]. The clinical presentation together with macroscopic and microscopic findings in a case of epidural fronto-parasagittal hemangiopericytoma occurring in a 59 years old female are reported. Pathogenesis, clinical and macroscopic findings, and microscopicaspects of this tumor aspected with the angioblastic (angiomatous) meningioma are discussed. The relevant literature is reviewed."} {"id": "PMID:1274702", "title": "[False aneurysm of the artery of the angular gyrus caused by vascular injury during ventricular puncture].", "content": "This description of a false aneurysm of the artery of the angular gyrus resulting from damage by a Cushing needle demonstrates the origin and the development of the lesion, and also its healing following thrombosis. The pathogenesis of the aneurysm is shown by illustrations of the angiographic findings and the histology.", "contents": "[False aneurysm of the artery of the angular gyrus caused by vascular injury during ventricular puncture]. This description of a false aneurysm of the artery of the angular gyrus resulting from damage by a Cushing needle demonstrates the origin and the development of the lesion, and also its healing following thrombosis. The pathogenesis of the aneurysm is shown by illustrations of the angiographic findings and the histology."} {"id": "PMID:1274703", "title": "The EEG in normal pressure hydrocephalus.", "content": "Fourteen patients with NPH were studied with special reference to associated EEG changes, one case being reported in detail. In 13 cases the EEG was abnormal, the abnormality most frequently observed being a of the rhythmic slow wave type, consisting of bursts of monorhythmic theta or delta waves seen in both hemispheres. This type of abnormality was present in 7 cases. In 4 of the 5 cases with serial EEG's the abnormality became more accentuated with the advance of the illness. In 4 of 5 cases in whom postoperative EEGs were obtained there was significant improvement of the EEG after the shunting procedure. There were stron correlations between the EEG abnormality described, demonstrable ventricular reflux on cisternography, and the effectiveness of the shunt operation. It was considered that serial EEGs are a useful diagnostic procedure in following up patients at risk of developing NPH.", "contents": "The EEG in normal pressure hydrocephalus. Fourteen patients with NPH were studied with special reference to associated EEG changes, one case being reported in detail. In 13 cases the EEG was abnormal, the abnormality most frequently observed being a of the rhythmic slow wave type, consisting of bursts of monorhythmic theta or delta waves seen in both hemispheres. This type of abnormality was present in 7 cases. In 4 of the 5 cases with serial EEG's the abnormality became more accentuated with the advance of the illness. In 4 of 5 cases in whom postoperative EEGs were obtained there was significant improvement of the EEG after the shunting procedure. There were stron correlations between the EEG abnormality described, demonstrable ventricular reflux on cisternography, and the effectiveness of the shunt operation. It was considered that serial EEGs are a useful diagnostic procedure in following up patients at risk of developing NPH."} {"id": "PMID:1274704", "title": "Telemetry of intracranial pressure.", "content": "A new technique is described for telemetric measurement of intracranial pressure in man using an external energy source and a small pressure transducer, called a TELECEPTOR, implanted in the skull. The method presents advantages, especially for long term recordings.", "contents": "Telemetry of intracranial pressure. A new technique is described for telemetric measurement of intracranial pressure in man using an external energy source and a small pressure transducer, called a TELECEPTOR, implanted in the skull. The method presents advantages, especially for long term recordings."} {"id": "PMID:1274705", "title": "Methodology for intraventricular and subarachnoid continuous recording of intracranial pressure in clinical practice.", "content": "The methodology for continuous monitoring intracranial pressure (ICP) being presently employed in the Neurosurgery Service of the University of Pennsylvania is presented. The methods are intraventricular recording of ICP (IVP) and subarachnoid recording of ICP (SaP). The indications for employing either method are briefly presented. IVP is favored in those situations in which the lateral ventricles are enlarged and SaP is preferred in the cases of brain swelling or other situations in which there is a small ventricular system.", "contents": "Methodology for intraventricular and subarachnoid continuous recording of intracranial pressure in clinical practice. The methodology for continuous monitoring intracranial pressure (ICP) being presently employed in the Neurosurgery Service of the University of Pennsylvania is presented. The methods are intraventricular recording of ICP (IVP) and subarachnoid recording of ICP (SaP). The indications for employing either method are briefly presented. IVP is favored in those situations in which the lateral ventricles are enlarged and SaP is preferred in the cases of brain swelling or other situations in which there is a small ventricular system."} {"id": "PMID:1274707", "title": "Surgical treatment of subdural effusions in infants.", "content": "We puropose a simplified method for external drainage of subdural effusions in infants, not calling for a second operation to remove the catheters. This method allows the daily control of evacuated fluid, guarantees smooth and uninterrupted drainage, and permits analysis of the subdural collection. This operation which we would like to call external controlled drainage, does not call for parenteral feeding, but demands paediatric and neurosurgical collaboration. The method has no pretensions other than being simple, easy, and safe.", "contents": "Surgical treatment of subdural effusions in infants. We puropose a simplified method for external drainage of subdural effusions in infants, not calling for a second operation to remove the catheters. This method allows the daily control of evacuated fluid, guarantees smooth and uninterrupted drainage, and permits analysis of the subdural collection. This operation which we would like to call external controlled drainage, does not call for parenteral feeding, but demands paediatric and neurosurgical collaboration. The method has no pretensions other than being simple, easy, and safe."} {"id": "PMID:1274708", "title": "Clinical study of chronic arachnoiditis in the posterior fossa.", "content": "A series of 12 cases of chronic arachnoiditis in the posterior fossa is reported. The diagnosis in six patients was established at suboccipital craniectomy whch brought about marked improvement in symptoms. The other six were diagnosed as having arachnoiditis in the posterior fossa from the facts that improvement in clinical symptoms was achieved by lumbar air insufflation, which has often been said to be effective in arachnoiditis, and no abnormal findings were revealed by pneumoencephalo-roulette tomography. By investigating the clinical features of these cases, we came to the following conclusions: many cases of this disease have had head trauma or chronic inflammatory disease in the past; the symptoms are apt to occur abruptly, and display repeated remission and aggravation; symptoms originating in the cranial nerves are diversified, and are often bilaterial; peripheral vestibular disturbances and retrocochlear hearing losses are observed on neuro-otological examination. In the caloric test especially the patients show canal paresis (CP) on the more impaired side, but none of them appeared to be nonresponsive to the test; lumbar air insufflation is often an effective treatment for this disease; pneumoencephalo-roulette tomography is very useful for diagnosing pathological changes in the posterior fossa.", "contents": "Clinical study of chronic arachnoiditis in the posterior fossa. A series of 12 cases of chronic arachnoiditis in the posterior fossa is reported. The diagnosis in six patients was established at suboccipital craniectomy whch brought about marked improvement in symptoms. The other six were diagnosed as having arachnoiditis in the posterior fossa from the facts that improvement in clinical symptoms was achieved by lumbar air insufflation, which has often been said to be effective in arachnoiditis, and no abnormal findings were revealed by pneumoencephalo-roulette tomography. By investigating the clinical features of these cases, we came to the following conclusions: many cases of this disease have had head trauma or chronic inflammatory disease in the past; the symptoms are apt to occur abruptly, and display repeated remission and aggravation; symptoms originating in the cranial nerves are diversified, and are often bilaterial; peripheral vestibular disturbances and retrocochlear hearing losses are observed on neuro-otological examination. In the caloric test especially the patients show canal paresis (CP) on the more impaired side, but none of them appeared to be nonresponsive to the test; lumbar air insufflation is often an effective treatment for this disease; pneumoencephalo-roulette tomography is very useful for diagnosing pathological changes in the posterior fossa."} {"id": "PMID:1274709", "title": "[Topgraphical classification of craniopharyngioma].", "content": "Squamous cell nests of Erdheim have been observed along the lateral blood vessels to the adenohypophysis in 4 cases. Their developmental origin and topographical distribution correlate with the sites in which craniopharyngiomas are found. The theory of dysontogenic origin of cranopharyngiomas is supported by these findings. Metaplasia of cells of the adenohypophysis is not considered to be a likely cause of craniopharyngioma formation.", "contents": "[Topgraphical classification of craniopharyngioma]. Squamous cell nests of Erdheim have been observed along the lateral blood vessels to the adenohypophysis in 4 cases. Their developmental origin and topographical distribution correlate with the sites in which craniopharyngiomas are found. The theory of dysontogenic origin of cranopharyngiomas is supported by these findings. Metaplasia of cells of the adenohypophysis is not considered to be a likely cause of craniopharyngioma formation."} {"id": "PMID:1274710", "title": "[Pulmonary changes in cranio-cerebral injuries and respiration with high oxygen concentrations].", "content": "In 131 cases of craniocerebral trauma it was shown in what respect definite changes in the lungs, demonstrated by clinical course, radiographs and blood gas analyses, occurred in proportion to the severity of the trauma. The causes of these changes were considered and the possibility of complicating the course of the illness by administering oxygen in high concentrations was investigated. In 98 patients was an indication for treatment with a respirator. 41 patients were so treated for longer than 5 days (mean 17.7 days). The need for respirator treatment rose with the increasing severity of the trauma. Frequency and severity of tracheobronchial aspiration increased in proportion to the depth of unconsciousness. It occurred in 50-60% of cases with severe trauma. Minor pulmonary lesions developed in 13% of those patients who only had minor disturbances of consciousness. Patients who had aspirated had lower arterial oxygen tensions than those who had not aspirated. In a high percentage of cases considerable improvement could be achieved, despite lung changes. In patients treated with the respirator mean inspiratory oxygen concentrations of 75% were necessary to achieve arterial oxygen tensions of 150-200 mm Hg. No evidence of oxygen toxicity was found, despite long periods of treatment with high oxygen concentrations. Very often cases of craniocerebral injury are followed both by tracheobronchial aspiration, causing lung damage, hypoxia and acidosis, and by disturbances of coagulation. These disorders are to be considered as most important, each needing specific therapy.", "contents": "[Pulmonary changes in cranio-cerebral injuries and respiration with high oxygen concentrations]. In 131 cases of craniocerebral trauma it was shown in what respect definite changes in the lungs, demonstrated by clinical course, radiographs and blood gas analyses, occurred in proportion to the severity of the trauma. The causes of these changes were considered and the possibility of complicating the course of the illness by administering oxygen in high concentrations was investigated. In 98 patients was an indication for treatment with a respirator. 41 patients were so treated for longer than 5 days (mean 17.7 days). The need for respirator treatment rose with the increasing severity of the trauma. Frequency and severity of tracheobronchial aspiration increased in proportion to the depth of unconsciousness. It occurred in 50-60% of cases with severe trauma. Minor pulmonary lesions developed in 13% of those patients who only had minor disturbances of consciousness. Patients who had aspirated had lower arterial oxygen tensions than those who had not aspirated. In a high percentage of cases considerable improvement could be achieved, despite lung changes. In patients treated with the respirator mean inspiratory oxygen concentrations of 75% were necessary to achieve arterial oxygen tensions of 150-200 mm Hg. No evidence of oxygen toxicity was found, despite long periods of treatment with high oxygen concentrations. Very often cases of craniocerebral injury are followed both by tracheobronchial aspiration, causing lung damage, hypoxia and acidosis, and by disturbances of coagulation. These disorders are to be considered as most important, each needing specific therapy."} {"id": "PMID:1274775", "title": "Effects outflow tract obstruction on total and regional coronary blood flow, and its influence on ventricular function.", "content": "Animal experiments suggest a model of coronary blood flow in which left ventricular subendocardial muscle is perfused only in diastole, while more superficial muscle is perfused throughout the cardiac cycle. Once maximal coronary vasodilatation has occured, subendocardial flow per minute depends on the area between aortic and left ventricular diastolic pressure time heart rate [DPTI per minute]. Since left ventricular oxygen needs are related to the area under the left ventricular pressure curve in systole [SPTI], the ratio DPTI/SPTI reflects balance between myocardial oxygen supply and demand. Marked reduction in the ratio causes relative subendocardial ischemia which can be predicted from teh ratio. There is evidence that outflow tract obstructions in man also cause subendocardial ischemia by similar mechanisms, and that this ischemia occurs despite normal coronary arteries.", "contents": "Effects outflow tract obstruction on total and regional coronary blood flow, and its influence on ventricular function. Animal experiments suggest a model of coronary blood flow in which left ventricular subendocardial muscle is perfused only in diastole, while more superficial muscle is perfused throughout the cardiac cycle. Once maximal coronary vasodilatation has occured, subendocardial flow per minute depends on the area between aortic and left ventricular diastolic pressure time heart rate [DPTI per minute]. Since left ventricular oxygen needs are related to the area under the left ventricular pressure curve in systole [SPTI], the ratio DPTI/SPTI reflects balance between myocardial oxygen supply and demand. Marked reduction in the ratio causes relative subendocardial ischemia which can be predicted from teh ratio. There is evidence that outflow tract obstructions in man also cause subendocardial ischemia by similar mechanisms, and that this ischemia occurs despite normal coronary arteries."} {"id": "PMID:1274778", "title": "Indications for and resluts of tricuspid valve replacement.", "content": "A review of our experience with tricuspid valve replacement over a 7.5-year period is presented. Isolated disease of the tricuspid valve was encountered infrequently [8 of 87 patients] and was due to a variety of causes. In the remaining cases, the tricuspid disease was associated with rheumatic valvular disease of the mitral and/or aortic valves. The hospital mortality for the entire group of patients was 22%, and the late mortality during a mean follow-up of 32 months was 16%. Operative and late mortality were clearly affected by the severity of myocardial dysfunction present preoperativley. Problems related to the prosthetic valves and to anticoagulant therapy were relatively few. Our present indications for replacement of the tricuspid valve and presented. Earlier operative intervention in patients with tricuspid valvular disease should improve the early and long-term results.", "contents": "Indications for and resluts of tricuspid valve replacement. A review of our experience with tricuspid valve replacement over a 7.5-year period is presented. Isolated disease of the tricuspid valve was encountered infrequently [8 of 87 patients] and was due to a variety of causes. In the remaining cases, the tricuspid disease was associated with rheumatic valvular disease of the mitral and/or aortic valves. The hospital mortality for the entire group of patients was 22%, and the late mortality during a mean follow-up of 32 months was 16%. Operative and late mortality were clearly affected by the severity of myocardial dysfunction present preoperativley. Problems related to the prosthetic valves and to anticoagulant therapy were relatively few. Our present indications for replacement of the tricuspid valve and presented. Earlier operative intervention in patients with tricuspid valvular disease should improve the early and long-term results."} {"id": "PMID:1274779", "title": "Indications for and results of surgery in congenital aortic stenosis.", "content": "All of the follow-up data indicate that aortic valvotomy is a safe and effective means of treatment. No instances of sudden death have been observed during the postoperative follow-up period. Of course, additional long-term studies of the results of surgery are indicated and it is certainly possible that the current criteria relating to indications for hemodynamic study and operation may well require modification in the future.", "contents": "Indications for and results of surgery in congenital aortic stenosis. All of the follow-up data indicate that aortic valvotomy is a safe and effective means of treatment. No instances of sudden death have been observed during the postoperative follow-up period. Of course, additional long-term studies of the results of surgery are indicated and it is certainly possible that the current criteria relating to indications for hemodynamic study and operation may well require modification in the future."} {"id": "PMID:1274782", "title": "Debate on valvular heart disease. Con: early surgical intervention in valvular heart disease.", "content": "Patients with valvular heart disease, particularly aortic and mitral incompetence, may have significant derangement of myocardial function, often in the absence of significant symptoms, which directly affects early and late survival and functional status following valve replacement. With declining hospital mortiality rates and improved valvular prostheses, consideration must be given to valve replacement in patients of this type in order to preserve myocardial function. This should improve long-term survival and the functional results following valve replacement. Attention should be directed to identifying and closely observing patients of this type, perhaps with noninvasive techniques, and proceeding with valve replacement before irreversible myocardial damage has occured.", "contents": "Debate on valvular heart disease. Con: early surgical intervention in valvular heart disease. Patients with valvular heart disease, particularly aortic and mitral incompetence, may have significant derangement of myocardial function, often in the absence of significant symptoms, which directly affects early and late survival and functional status following valve replacement. With declining hospital mortiality rates and improved valvular prostheses, consideration must be given to valve replacement in patients of this type in order to preserve myocardial function. This should improve long-term survival and the functional results following valve replacement. Attention should be directed to identifying and closely observing patients of this type, perhaps with noninvasive techniques, and proceeding with valve replacement before irreversible myocardial damage has occured."} {"id": "PMID:1274784", "title": "Indications for and results of surgery in ventricular septal defects.", "content": "Surgical closure of VSDs is indicated mainly for those that are larger and causing either servere congestive heart failure or else pulmonary vascular disease. The latter, producing an increased pulmonary vascular resistance, is usually reversible if the VSD is closed under 2 years of age, but may become irreversible if left for longer times. Primary closure of the VSD, even in infants is in many centers done with a lower mortality than banding of the pulmonary artery and late VSD repair. Selection of patients needs great care because VSDs frequently get smaller or close spontaneously, even if initially large.", "contents": "Indications for and results of surgery in ventricular septal defects. Surgical closure of VSDs is indicated mainly for those that are larger and causing either servere congestive heart failure or else pulmonary vascular disease. The latter, producing an increased pulmonary vascular resistance, is usually reversible if the VSD is closed under 2 years of age, but may become irreversible if left for longer times. Primary closure of the VSD, even in infants is in many centers done with a lower mortality than banding of the pulmonary artery and late VSD repair. Selection of patients needs great care because VSDs frequently get smaller or close spontaneously, even if initially large."} {"id": "PMID:1274786", "title": "Interpretation and limitations in stress testing.", "content": "In summary, although exercise is, as is every other procedure, imperfect with regard to sensitivity and specificity, it provides an invalualbe adjunct in the evaluation of patients with coronary disease. The test is simple, inexpensive, safe and rapidly performed and is an invaluable aid in screening patients with possible coronary disease. It is used in an asymptomatic population for industrial purposes, is useful in assessing the etiology of otherwise undiagnosed chest pain, helpful in evaluating the overall severity of ischemia [and therefore in culling-out those patients that might benefit from coronary angiography], is useful in following the course of patients with proven coronary disease [including those with acute myocardial infarction], and has found a place in the follow-up evaluation of individuals having aortocoronary bypass surgery. As a screening procedure, the treadmill test aids in seeking out that group of patients with coronary disease with potentially malignant lesions, i.e. main left coronary lesions, triple-vessel disease and [to a lesser extent] severe proximal left anterior descending coronary disease. Hence, the finding of marked depth of ST depression, prolonged duration of ischemia associated with deep ST segments, serious exercise-induced ventricular arrhythmias and hypotension produced during mild-to-moderate exercise might each be an indication of extensive coronary angiography. In many cases exercise testing is superior to coronary angiography, being a simpler, safer screening procedure, and a more functional test in documenting the presence or absence of coronary insufficiency.", "contents": "Interpretation and limitations in stress testing. In summary, although exercise is, as is every other procedure, imperfect with regard to sensitivity and specificity, it provides an invalualbe adjunct in the evaluation of patients with coronary disease. The test is simple, inexpensive, safe and rapidly performed and is an invaluable aid in screening patients with possible coronary disease. It is used in an asymptomatic population for industrial purposes, is useful in assessing the etiology of otherwise undiagnosed chest pain, helpful in evaluating the overall severity of ischemia [and therefore in culling-out those patients that might benefit from coronary angiography], is useful in following the course of patients with proven coronary disease [including those with acute myocardial infarction], and has found a place in the follow-up evaluation of individuals having aortocoronary bypass surgery. As a screening procedure, the treadmill test aids in seeking out that group of patients with coronary disease with potentially malignant lesions, i.e. main left coronary lesions, triple-vessel disease and [to a lesser extent] severe proximal left anterior descending coronary disease. Hence, the finding of marked depth of ST depression, prolonged duration of ischemia associated with deep ST segments, serious exercise-induced ventricular arrhythmias and hypotension produced during mild-to-moderate exercise might each be an indication of extensive coronary angiography. In many cases exercise testing is superior to coronary angiography, being a simpler, safer screening procedure, and a more functional test in documenting the presence or absence of coronary insufficiency."} {"id": "PMID:1274788", "title": "Study of drugs affecting cholesterol-induced atherosclerosis in rabbits.", "content": "1. Effects of various drugs on cholesterol-induced atherosclerosis in rabbits during the progression phase have been studied. The drugs tested are antimetabolites (mercaptopurine, hydroxyurea), surface active agents (sodiumdodecyl sulfate), inhibitor of adrenocoritcal steroid synthesis (o, p'-DDD), lysosome stablizers (chloroquine, acetylsalicylic acid) with antihistaminic (chlorpheniramine) and cholesterol binder (nystatin). 2. Mercaptopurine treatment showed marekd reduction in both atherosclerotic lesions and cholesterol concentrations of the serum and aorta. 3. Hydroxyurea reduced both the aortic cholesterol concentration and the lesions, but the serum cholesterol concentration remained high. 4. Sodiumdodecyl sulfate and o, o'-DDD showed slight inhibition of the development of atherosclerosis. 5. Pyridinocarbamate showed a slight beneficial effect on the prevention of atherosclerosis only when it was administered prior to the meal. 6. Nystatin, chloroquine and acetylsalicylic acid + chlorpheniramine showed little effect.", "contents": "Study of drugs affecting cholesterol-induced atherosclerosis in rabbits. 1. Effects of various drugs on cholesterol-induced atherosclerosis in rabbits during the progression phase have been studied. The drugs tested are antimetabolites (mercaptopurine, hydroxyurea), surface active agents (sodiumdodecyl sulfate), inhibitor of adrenocoritcal steroid synthesis (o, p'-DDD), lysosome stablizers (chloroquine, acetylsalicylic acid) with antihistaminic (chlorpheniramine) and cholesterol binder (nystatin). 2. Mercaptopurine treatment showed marekd reduction in both atherosclerotic lesions and cholesterol concentrations of the serum and aorta. 3. Hydroxyurea reduced both the aortic cholesterol concentration and the lesions, but the serum cholesterol concentration remained high. 4. Sodiumdodecyl sulfate and o, o'-DDD showed slight inhibition of the development of atherosclerosis. 5. Pyridinocarbamate showed a slight beneficial effect on the prevention of atherosclerosis only when it was administered prior to the meal. 6. Nystatin, chloroquine and acetylsalicylic acid + chlorpheniramine showed little effect."} {"id": "PMID:1274790", "title": "Cholestero metabolism in rats sensitive to high cholesterol diet.", "content": "There was great individual variation in the elevations of serum cholesterol concentrations in a Wistar strain of rats by the ingestion of a large amount of cholesterol, although their cholesterol concentrations were almost identical while under the feeding of a regular stock diet. Their serum total phospholipid and dextran precipitable beta-lipoproteins showed the same tendencies, but serum triglycerids concentration was not affected by the dietary supplement in both groups. So, the rats with the different elevation rates of serum cholesterol concentrations were divided into good, normo and poor responding groups to cholesterol ingestion by the degrees of the elvations and bred for several generations. Serum lipid levels in the descendants from hyperresponding rats were not different from those from hyporesponding rats during the observed period, when they were given a stock diet. However, the response of serum cholesterol level to oral cholesterol ingestion in the former was larger than that in the latter. Therefore, it is suggested that the susceptibility of serum cholesterol to cholesterol ingestion may be heritable from parents to their offsprings. By the results of the tracer experiments, it was demonstrated that neither hepatic cholesterol synthesis nor absorption was affected in hyperresponding rats. On the other hand, a half life of labeled cholesterol was prolonged in this selected group. The relative fractional turnover rate was 17.8 per cent in hyporesponding rats and 15.8 per cent in hyperresponding rats. Excretion of the radioactivity from labeled cholesterol into the bile in good responding rats with bile fistula was slower than that in poor responding rats. When 1 g per 100 g body weight of glucose was given to the rats after 40 hours fasting, hepatic cholesterol synthesis increased at the same rate in both groups of rats, but the induction of hepatic cholesterol 7alpha-hydroxylation in hyperresponding groups was slower than that in hyporesponding groups. The distribution rates of the radioactivities into livers seemed to be delayed in good responders after the labeled cholesterol was ingested orally.It means that some disturbances in cholesterol transport may exist which induce the metabolic abnormality in such animals. It was shown that cholesterol metabolism was impaired in aged animals as compared with young ones. Serum cholesterol concentrations were elevated in good responders more than in poor responders by aging. The inborn errors of cholesterol metabolism in such animals might be emphasized from the fact of the impairment of cholesterol metabolism by the aging process.", "contents": "Cholestero metabolism in rats sensitive to high cholesterol diet. There was great individual variation in the elevations of serum cholesterol concentrations in a Wistar strain of rats by the ingestion of a large amount of cholesterol, although their cholesterol concentrations were almost identical while under the feeding of a regular stock diet. Their serum total phospholipid and dextran precipitable beta-lipoproteins showed the same tendencies, but serum triglycerids concentration was not affected by the dietary supplement in both groups. So, the rats with the different elevation rates of serum cholesterol concentrations were divided into good, normo and poor responding groups to cholesterol ingestion by the degrees of the elvations and bred for several generations. Serum lipid levels in the descendants from hyperresponding rats were not different from those from hyporesponding rats during the observed period, when they were given a stock diet. However, the response of serum cholesterol level to oral cholesterol ingestion in the former was larger than that in the latter. Therefore, it is suggested that the susceptibility of serum cholesterol to cholesterol ingestion may be heritable from parents to their offsprings. By the results of the tracer experiments, it was demonstrated that neither hepatic cholesterol synthesis nor absorption was affected in hyperresponding rats. On the other hand, a half life of labeled cholesterol was prolonged in this selected group. The relative fractional turnover rate was 17.8 per cent in hyporesponding rats and 15.8 per cent in hyperresponding rats. Excretion of the radioactivity from labeled cholesterol into the bile in good responding rats with bile fistula was slower than that in poor responding rats. When 1 g per 100 g body weight of glucose was given to the rats after 40 hours fasting, hepatic cholesterol synthesis increased at the same rate in both groups of rats, but the induction of hepatic cholesterol 7alpha-hydroxylation in hyperresponding groups was slower than that in hyporesponding groups. The distribution rates of the radioactivities into livers seemed to be delayed in good responders after the labeled cholesterol was ingested orally.It means that some disturbances in cholesterol transport may exist which induce the metabolic abnormality in such animals. It was shown that cholesterol metabolism was impaired in aged animals as compared with young ones. Serum cholesterol concentrations were elevated in good responders more than in poor responders by aging. The inborn errors of cholesterol metabolism in such animals might be emphasized from the fact of the impairment of cholesterol metabolism by the aging process."} {"id": "PMID:1274793", "title": "Produced by selective breeding of Japanese quail animal model for experimental atherosclerosis.", "content": "The Japanese quail (Coturnix coturnix japonica) was bred selectively to produce a strain highly susceptible to experimental atherosclerosis. A population was produced where aortic atherosclerosis is contracted by 99% of the fourth generation males and 83% of the femlaes. Forty-three percent of the males exhibited severe atherosclerosis making this line of Japanese quail a suitable model for discovering and testing anti-atherosclerosis compounds. This feature is augmented by other features such as size, disposition, and abundance which qualify them as suitable experimental subjects. A second line of Japanese quail was bred to be resistant to dietary-induced atherosclerosis. This strain may be a useful research tool for characterizing the etiology of atherosclerosis.", "contents": "Produced by selective breeding of Japanese quail animal model for experimental atherosclerosis. The Japanese quail (Coturnix coturnix japonica) was bred selectively to produce a strain highly susceptible to experimental atherosclerosis. A population was produced where aortic atherosclerosis is contracted by 99% of the fourth generation males and 83% of the femlaes. Forty-three percent of the males exhibited severe atherosclerosis making this line of Japanese quail a suitable model for discovering and testing anti-atherosclerosis compounds. This feature is augmented by other features such as size, disposition, and abundance which qualify them as suitable experimental subjects. A second line of Japanese quail was bred to be resistant to dietary-induced atherosclerosis. This strain may be a useful research tool for characterizing the etiology of atherosclerosis."} {"id": "PMID:1274794", "title": "A mechanism for lipid accumulation and central necrosis in fibrous plaques.", "content": "This is a step section study of 3 fibrous plaques from the abdominal aorta of an ostrich. The distribution of gelatinous like lesions in these plaques suggested that the gelatinous lesions were formed by the influx of plasma at the plaque shoulders. Two gelatinous lesions extended like tunnels into the center of one of the plaques. The presence of focal necrosis and large cholesterol crystals in one of these gelatinous tunnels deep within the plaque suggested that gelatinous lesions might represent one mechanism by which fibrous plaques are converted to atheromatous plaques.", "contents": "A mechanism for lipid accumulation and central necrosis in fibrous plaques. This is a step section study of 3 fibrous plaques from the abdominal aorta of an ostrich. The distribution of gelatinous like lesions in these plaques suggested that the gelatinous lesions were formed by the influx of plasma at the plaque shoulders. Two gelatinous lesions extended like tunnels into the center of one of the plaques. The presence of focal necrosis and large cholesterol crystals in one of these gelatinous tunnels deep within the plaque suggested that gelatinous lesions might represent one mechanism by which fibrous plaques are converted to atheromatous plaques."} {"id": "PMID:1274796", "title": "The baboon in atherosclerosis research: comparison with other species and use in testing drugs affecting lipid metabolism.", "content": "Despite the deomnstration of spontaneous atherosclerosis in the wild state, the baboon is not the best species for the production of atherosclerosis experimentally since it develops only a mild hypercholesterolaemia when fed cholesterol. Nevertheless, it is useful for the study of mild lipid deposition in the aorta and the effect of drugs thereon, particularly if protein antigens are also employed in addition. For studies of the hypocholesterolaemic effect of potential therapeutic compounds in man, the baboon fed a high protein commercial diet, with and without cholesterol, is a useful second species to smaller laboratory animals.", "contents": "The baboon in atherosclerosis research: comparison with other species and use in testing drugs affecting lipid metabolism. Despite the deomnstration of spontaneous atherosclerosis in the wild state, the baboon is not the best species for the production of atherosclerosis experimentally since it develops only a mild hypercholesterolaemia when fed cholesterol. Nevertheless, it is useful for the study of mild lipid deposition in the aorta and the effect of drugs thereon, particularly if protein antigens are also employed in addition. For studies of the hypocholesterolaemic effect of potential therapeutic compounds in man, the baboon fed a high protein commercial diet, with and without cholesterol, is a useful second species to smaller laboratory animals."} {"id": "PMID:1274797", "title": "Factors predicting mortality in the elderly in the community.", "content": "Factors which best predict mortality within five years have been examined in a random community sample of 852 people over 65. Apart from sex, multiple-regression analysis shows the best predictive factors to be higher age and the occurrence of proteinuria in both sexes. In men, low vitamin c intake and an unfavourable clinician's assessment of the subject's health were also significant predictors. In women, whether the subject was housebound, the diagnoses of stroke and of diabetes and a low serum pyridoxine were additional adverse factors. The findings regarding low vitamin C intake in men and low serum pyridoxine levels in women should be regarded with caution. The former appears unlikely to represent a true vitamin deficiency effect and whilst the latter might, the evidence is no more than suggestive and further confirmatory studies are required.", "contents": "Factors predicting mortality in the elderly in the community. Factors which best predict mortality within five years have been examined in a random community sample of 852 people over 65. Apart from sex, multiple-regression analysis shows the best predictive factors to be higher age and the occurrence of proteinuria in both sexes. In men, low vitamin c intake and an unfavourable clinician's assessment of the subject's health were also significant predictors. In women, whether the subject was housebound, the diagnoses of stroke and of diabetes and a low serum pyridoxine were additional adverse factors. The findings regarding low vitamin C intake in men and low serum pyridoxine levels in women should be regarded with caution. The former appears unlikely to represent a true vitamin deficiency effect and whilst the latter might, the evidence is no more than suggestive and further confirmatory studies are required."} {"id": "PMID:1274798", "title": "Red-blood-cell potassium and hand-grip strength in healthy elderly people.", "content": "Red-blood-cell potassium (RBCK) as an indicator of body potassium status was measured in 103 healthy elderly subjects over the age of 65 years. There was no correlation between RBCK and grip strength. The only significant predictors of grip strength were age and sex. The RBCK values formed a single normal distribution. There was no hypokalaemic subpopulation such as would be expected if potassium deficiency were common in these old people.", "contents": "Red-blood-cell potassium and hand-grip strength in healthy elderly people. Red-blood-cell potassium (RBCK) as an indicator of body potassium status was measured in 103 healthy elderly subjects over the age of 65 years. There was no correlation between RBCK and grip strength. The only significant predictors of grip strength were age and sex. The RBCK values formed a single normal distribution. There was no hypokalaemic subpopulation such as would be expected if potassium deficiency were common in these old people."} {"id": "PMID:1274799", "title": "The causes of osteomalacia in the elderly.", "content": "Investigations into the causes of osteomalacia in 12 geriatric patients with a histologically proven diagnosis, revealed no predominant aetiology. The metabolic bone disease in these patients appeared to have multifactorial causes in at least half the cases.", "contents": "The causes of osteomalacia in the elderly. Investigations into the causes of osteomalacia in 12 geriatric patients with a histologically proven diagnosis, revealed no predominant aetiology. The metabolic bone disease in these patients appeared to have multifactorial causes in at least half the cases."} {"id": "PMID:1274800", "title": "Myocardial contractility in aged rats.", "content": "The elastic and mechanical behaviour of isolated papillar muscle was studied in aged and in young rats. The spontaneous fall in tension (stress relaxation phenomenon) and the duration of the active state of the contractile element during the isometric and isotonic contraction were greater in aged than in young rats. The elastic properties of the elements in parallel and in series and the intensity of the active state in the contractile elements, on the contrary, did not exhibit any significant difference between aged and young rats.", "contents": "Myocardial contractility in aged rats. The elastic and mechanical behaviour of isolated papillar muscle was studied in aged and in young rats. The spontaneous fall in tension (stress relaxation phenomenon) and the duration of the active state of the contractile element during the isometric and isotonic contraction were greater in aged than in young rats. The elastic properties of the elements in parallel and in series and the intensity of the active state in the contractile elements, on the contrary, did not exhibit any significant difference between aged and young rats."} {"id": "PMID:1274802", "title": "Caring for relatives of stroke patients.", "content": "The methods used by the Rehabilitation Unit of the Repatriation General Hospital, Daw Park, to involve relatives of stroke patients in the rehabilitation process are outlined. The use of group therapy techniques for relatives is described and the issues commonly encountered are discussed. The value of the group meetings for relatives and staff is emphasized.", "contents": "Caring for relatives of stroke patients. The methods used by the Rehabilitation Unit of the Repatriation General Hospital, Daw Park, to involve relatives of stroke patients in the rehabilitation process are outlined. The use of group therapy techniques for relatives is described and the issues commonly encountered are discussed. The value of the group meetings for relatives and staff is emphasized."} {"id": "PMID:1274803", "title": "Sweat responses in the aged.", "content": "The sweating responses to thermal stimulation and to the intradermal injection of acetyl choline or methacholine were measured in 28 men and 18 women aged 70 and over and were compared with the responses in young control subjects of both sexes. There was found to be a marked reduction in the sweating activity of the majority of aged men in comparison with the younger age groups and the body temperature threshold for the onset of sweating was increased. The reduced response and elevated threshold were even more pronounced in aged females. There is considerable variability in response in different subjects and at different bodily sites. Impairment of thermoregulatory function due to diminished or absent sweating is thought to be one of the factors responsible for increased mortality in the elderly population during heat-waves.", "contents": "Sweat responses in the aged. The sweating responses to thermal stimulation and to the intradermal injection of acetyl choline or methacholine were measured in 28 men and 18 women aged 70 and over and were compared with the responses in young control subjects of both sexes. There was found to be a marked reduction in the sweating activity of the majority of aged men in comparison with the younger age groups and the body temperature threshold for the onset of sweating was increased. The reduced response and elevated threshold were even more pronounced in aged females. There is considerable variability in response in different subjects and at different bodily sites. Impairment of thermoregulatory function due to diminished or absent sweating is thought to be one of the factors responsible for increased mortality in the elderly population during heat-waves."} {"id": "PMID:1274808", "title": "Recognizing oral lesions.", "content": "Common benign lesions include hemagniomas and congenital cysts, pyogenic granuloma, aphthous ulcer, fibromas and changes produced by drugs. Many of these are self-limited and of little consequence. The point of the careful examination is the early detection of oral cancer. Only one patient in three with oral cavity cancer is cured. Premalignant and early asymptomatic lesions must be detected. Recognize the high-risk patient and examine the oral cavity meticulously.", "contents": "Recognizing oral lesions. Common benign lesions include hemagniomas and congenital cysts, pyogenic granuloma, aphthous ulcer, fibromas and changes produced by drugs. Many of these are self-limited and of little consequence. The point of the careful examination is the early detection of oral cancer. Only one patient in three with oral cavity cancer is cured. Premalignant and early asymptomatic lesions must be detected. Recognize the high-risk patient and examine the oral cavity meticulously."} {"id": "PMID:1274809", "title": "Psychiatric aspects of intestinal bypass surgery for obesity.", "content": "Intestinal bypass patients were studied six and 30 months postoperatively with regard to medical morbidity, weight loss and psychologic and behavioral adjustments. In general, at 30 months they were more stable and productive. Their expectations in terms of weight loss and psychologic changes may not have been met; yet, a majority of them have recommended the operation to others. Preoperative selection criteria will help physicians choose good candidates and discourage the others. Long-term follow-up is essential.", "contents": "Psychiatric aspects of intestinal bypass surgery for obesity. Intestinal bypass patients were studied six and 30 months postoperatively with regard to medical morbidity, weight loss and psychologic and behavioral adjustments. In general, at 30 months they were more stable and productive. Their expectations in terms of weight loss and psychologic changes may not have been met; yet, a majority of them have recommended the operation to others. Preoperative selection criteria will help physicians choose good candidates and discourage the others. Long-term follow-up is essential."} {"id": "PMID:1274810", "title": "Injuries from rotary power lawnmowers.", "content": "Injuries from power lawnmowers most frequently involve the toes or the foot. The most common injury is caused by an extremity being caught in the moving parts of the machine. The greatest injury is to the skin and soft tissue by degloving or avulsion. Most of these injuries, especially those which occur to children who are passengers on self-propelled mowers, are preventable by observance of simple precautions.", "contents": "Injuries from rotary power lawnmowers. Injuries from power lawnmowers most frequently involve the toes or the foot. The most common injury is caused by an extremity being caught in the moving parts of the machine. The greatest injury is to the skin and soft tissue by degloving or avulsion. Most of these injuries, especially those which occur to children who are passengers on self-propelled mowers, are preventable by observance of simple precautions."} {"id": "PMID:1274811", "title": "Medical management of urolithiasis.", "content": "Knowledge of the crystalline structure of the calculus provides the basis of the therapeutic plan. Laboratory evaluation depends heavily upon routine urinalysis. Assessment of renal function, serum calcium, phosphorus, uric acid and, in some cases electrolytes is usually indicated, as is urography. General principles of management include maintenance of an ample urine volume, eradication of infection and correction of any obstructing lesions or metabolic abnormalities. Specific antistone regimens are indicated for patients with recurrent urolithiasis.", "contents": "Medical management of urolithiasis. Knowledge of the crystalline structure of the calculus provides the basis of the therapeutic plan. Laboratory evaluation depends heavily upon routine urinalysis. Assessment of renal function, serum calcium, phosphorus, uric acid and, in some cases electrolytes is usually indicated, as is urography. General principles of management include maintenance of an ample urine volume, eradication of infection and correction of any obstructing lesions or metabolic abnormalities. Specific antistone regimens are indicated for patients with recurrent urolithiasis."} {"id": "PMID:1274812", "title": "Physostigmine treatment of delirium induced by anticholinergics.", "content": "Medication with anticholinergic properties are used commonly in family practice. Toxic delirium, which may resemble an acute psychosis, can occur as an adverse drug reaction to properly prescribed anticholingeric medication and to recommended doses of many patent medicines. More frequently it is due to overdosage. The key to diagnosis is the presence of peripheral signs of parasympathetic blockade. Delirium induced by anticholinergic drugs can be treated rapidly and effectively with physostigmine salicylate.", "contents": "Physostigmine treatment of delirium induced by anticholinergics. Medication with anticholinergic properties are used commonly in family practice. Toxic delirium, which may resemble an acute psychosis, can occur as an adverse drug reaction to properly prescribed anticholingeric medication and to recommended doses of many patent medicines. More frequently it is due to overdosage. The key to diagnosis is the presence of peripheral signs of parasympathetic blockade. Delirium induced by anticholinergic drugs can be treated rapidly and effectively with physostigmine salicylate."} {"id": "PMID:1274815", "title": "Stress fractures.", "content": "Stress fractures, well-known occurrences in military recruits, also occur in civilians. There is a gradual alteration of the bone resulting from repeated unaccustomed stresses. Pain usually precedes positive x-rays by one to two weeks. Serial films are therefore required. Differential diagnosis can be a problem but treatment is simple. Femoral neck stress fractures can become complicated.", "contents": "Stress fractures. Stress fractures, well-known occurrences in military recruits, also occur in civilians. There is a gradual alteration of the bone resulting from repeated unaccustomed stresses. Pain usually precedes positive x-rays by one to two weeks. Serial films are therefore required. Differential diagnosis can be a problem but treatment is simple. Femoral neck stress fractures can become complicated."} {"id": "PMID:1274816", "title": "Group care for psychiatric patients.", "content": "The family physician and one or two office staff members or associates can conveniently and effectively provide ongoing care for a large group of reasonably stable, yet severely disturbed, psychiatric patients. The main goal is to promote successful integration into meaningful family and community relationships. In many cases, the family physician is the most appropriate health professional to provide this care, due to his knowledge of the patient's family, community situation and physical health.", "contents": "Group care for psychiatric patients. The family physician and one or two office staff members or associates can conveniently and effectively provide ongoing care for a large group of reasonably stable, yet severely disturbed, psychiatric patients. The main goal is to promote successful integration into meaningful family and community relationships. In many cases, the family physician is the most appropriate health professional to provide this care, due to his knowledge of the patient's family, community situation and physical health."} {"id": "PMID:1274817", "title": "Psychologic factors associated with obesity.", "content": "Obesity, particularly of the juvenile-onset type, is often associated with anger and anxiety underlying a facade of joviality. There may be marked disturbances of body image. Regardless of whether psychologic factors are the cause or result of obesity, they must be considered if efforts at weight reduction are to be successful. Substitutes for the gratification of food must be provided.", "contents": "Psychologic factors associated with obesity. Obesity, particularly of the juvenile-onset type, is often associated with anger and anxiety underlying a facade of joviality. There may be marked disturbances of body image. Regardless of whether psychologic factors are the cause or result of obesity, they must be considered if efforts at weight reduction are to be successful. Substitutes for the gratification of food must be provided."} {"id": "PMID:1274818", "title": "Evaluation of the infertile couple.", "content": "Infertility may be caused by gross pelvic pathology, difficulties with insemination of the cervix and uterine cavity, partial or complete occlusion of the fallopian tubes, female endocrine abnormalities or male factors. Some forms of pelvic pathology as well as some tubal occlusions are amenable to surgical correction. Clomiphene citrate has given good results in some patients with endocrine abnormalities.", "contents": "Evaluation of the infertile couple. Infertility may be caused by gross pelvic pathology, difficulties with insemination of the cervix and uterine cavity, partial or complete occlusion of the fallopian tubes, female endocrine abnormalities or male factors. Some forms of pelvic pathology as well as some tubal occlusions are amenable to surgical correction. Clomiphene citrate has given good results in some patients with endocrine abnormalities."} {"id": "PMID:1274820", "title": "Atrial T(Ta) wave and atrial gradient in patients with A-V block.", "content": "The P and the Ta waves of two patient groups with A-V block were magnified with a direct-current amplifier and recorded at a high paper speed. In Group A patients (those without serious cardiovascular complications except A-V block) the P and the Ta waves were recorded in the opposite direction in every lead and there was a linear relationship between the amplitude of the P and the Ta waves. The atrial gradient was nearly zero. There existed a positive correlation between the P + Ta time and the P-P interval. In Group B patients (those with serious cardiovascular complications besides A-V block) there were significant differences in the Ta wave from Group A with respect to form, polarity, amplitude, duration, and the relationship between the Ta and the P waves. The atrial gradient was markedly large. Careful attention should be paid to the deviation of the PQ segment caused by the Ta wave in daily ECG's to detect atrial abnormalities. The Ta wave extends into the ST segment and, while describing the deviation of the ST segment, the influence of the Ta wave should be kept in mind.", "contents": "Atrial T(Ta) wave and atrial gradient in patients with A-V block. The P and the Ta waves of two patient groups with A-V block were magnified with a direct-current amplifier and recorded at a high paper speed. In Group A patients (those without serious cardiovascular complications except A-V block) the P and the Ta waves were recorded in the opposite direction in every lead and there was a linear relationship between the amplitude of the P and the Ta waves. The atrial gradient was nearly zero. There existed a positive correlation between the P + Ta time and the P-P interval. In Group B patients (those with serious cardiovascular complications besides A-V block) there were significant differences in the Ta wave from Group A with respect to form, polarity, amplitude, duration, and the relationship between the Ta and the P waves. The atrial gradient was markedly large. Careful attention should be paid to the deviation of the PQ segment caused by the Ta wave in daily ECG's to detect atrial abnormalities. The Ta wave extends into the ST segment and, while describing the deviation of the ST segment, the influence of the Ta wave should be kept in mind."} {"id": "PMID:1274821", "title": "The effects of smoking on myocardial conduction in the human heart.", "content": "Inhalation of a few puffs on a cigarette increases the velocity of conduction and shortens the effective refractory period of the A-V node. These effects are attributed to adrenergic stimulation produced by minute amounts of nicotine absorbed. Wenckebach block is abolished whether induced by atrial pacing or occurring spontaneously. Conduction velocity in the His-Purkinje system and in the anomalous pathways in the WPW syndrome were not affected. Smoking increases the ventricular rate in atrial fibrillation, and antagonizes the cholinergic effects of digitalis.", "contents": "The effects of smoking on myocardial conduction in the human heart. Inhalation of a few puffs on a cigarette increases the velocity of conduction and shortens the effective refractory period of the A-V node. These effects are attributed to adrenergic stimulation produced by minute amounts of nicotine absorbed. Wenckebach block is abolished whether induced by atrial pacing or occurring spontaneously. Conduction velocity in the His-Purkinje system and in the anomalous pathways in the WPW syndrome were not affected. Smoking increases the ventricular rate in atrial fibrillation, and antagonizes the cholinergic effects of digitalis."} {"id": "PMID:1274822", "title": "Comparison of selective left ventriculograms with levophase (\"forward\") ventriculograms in patients with coronary artery disease.", "content": "In order to compare levophase (\"forward\") ventriculograms to standard (selective) LV cineangiography, 10 patients with coronary artery disease were studied by (1) selective injection of contrast medium into the LV cavity followed by (2) injection into the right ventricle and filming the levophase. Biplane cineangiograms were used to calculate the end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI), and ejection fraction (EF). Values for the two respective techniques were then compared. Not only were correlation coefficients for the two methods low, but there was also a statistically significant difference between the two SVI (66 +/- 26 ml. for selective and 53 +/- 25 ml. for levophase injection; p less than 0.02) and the two EF (67 +/- 7 per cent for selective and 52 +/- 12 per cent for levophase injection; p less than 0.01). Levophase cineangiograms therefore significantly underestimate the LV ejection fraction when compared to standard (selective) LV cineangiography. These differences must be considered when evaluating greatly divergent interinstitutional survival rates for patients with low EF who undergo coronary artery bypass surgery, and when selecting candidates for bypass surgery on the basis of the angiographic data.", "contents": "Comparison of selective left ventriculograms with levophase (\"forward\") ventriculograms in patients with coronary artery disease. In order to compare levophase (\"forward\") ventriculograms to standard (selective) LV cineangiography, 10 patients with coronary artery disease were studied by (1) selective injection of contrast medium into the LV cavity followed by (2) injection into the right ventricle and filming the levophase. Biplane cineangiograms were used to calculate the end-diastolic volume index (EDVI), end-systolic volume index (ESVI), stroke volume index (SVI), and ejection fraction (EF). Values for the two respective techniques were then compared. Not only were correlation coefficients for the two methods low, but there was also a statistically significant difference between the two SVI (66 +/- 26 ml. for selective and 53 +/- 25 ml. for levophase injection; p less than 0.02) and the two EF (67 +/- 7 per cent for selective and 52 +/- 12 per cent for levophase injection; p less than 0.01). Levophase cineangiograms therefore significantly underestimate the LV ejection fraction when compared to standard (selective) LV cineangiography. These differences must be considered when evaluating greatly divergent interinstitutional survival rates for patients with low EF who undergo coronary artery bypass surgery, and when selecting candidates for bypass surgery on the basis of the angiographic data."} {"id": "PMID:1274823", "title": "Relationship between duration of systolic upstroke of apexcardiogram and internal indexes of myocardial function in man.", "content": "In 11 patients with nonobstructive cardiomyopathy and coronary heart disease and decreased myocardial function of the left ventricle, as well as in nine patients without left heart valvular or myocardial disease, left apexcardiograms were recorded during diagnostic heart catheterization, wherein micromanometers were used; ACG's were registered additionally in 54 healthy volunteers in order to establish the normal range of apexcardiographic parameters. In all cases the apex tracings were recorded by means of a pulse transducer with infinite time constant. The most important finding of this study was the close correlation between the duration of the systolic upstroke (SUT) of the apex tracing and some accepted isovolumic indexes of left heart function (isovolumic contraction time, time interval from the onset to peak of the first derivative of left ventricular pressure, maximal value of the first derivative of left ventricular pressure, and the peak measured velocity of shortening of the contractile elements). Further, the mean value of SUT in patients with impaired left myocardial function was significantly prolonged, compared to the control subjects; an overlap was apparent due to the fact that some of these patients showed a normal left myocardial performance at rest, having an abnormal response only to exercise tests. The apexcardiographic SUT can practically always be measured when the first derivative of apex tracing is simultaneously recorded. It showed itself to be only slightly influenced by the resting heart rate. The mentioned relationship of the systolic upstroke time of the ACG to internal isovolumic indexes of myocardial function makes this noninvasive measurable parameter an additional excellent tool for the evaluation of the left myocardial state, thus supporting a new aspect of the value of quantitative apexcardiography.", "contents": "Relationship between duration of systolic upstroke of apexcardiogram and internal indexes of myocardial function in man. In 11 patients with nonobstructive cardiomyopathy and coronary heart disease and decreased myocardial function of the left ventricle, as well as in nine patients without left heart valvular or myocardial disease, left apexcardiograms were recorded during diagnostic heart catheterization, wherein micromanometers were used; ACG's were registered additionally in 54 healthy volunteers in order to establish the normal range of apexcardiographic parameters. In all cases the apex tracings were recorded by means of a pulse transducer with infinite time constant. The most important finding of this study was the close correlation between the duration of the systolic upstroke (SUT) of the apex tracing and some accepted isovolumic indexes of left heart function (isovolumic contraction time, time interval from the onset to peak of the first derivative of left ventricular pressure, maximal value of the first derivative of left ventricular pressure, and the peak measured velocity of shortening of the contractile elements). Further, the mean value of SUT in patients with impaired left myocardial function was significantly prolonged, compared to the control subjects; an overlap was apparent due to the fact that some of these patients showed a normal left myocardial performance at rest, having an abnormal response only to exercise tests. The apexcardiographic SUT can practically always be measured when the first derivative of apex tracing is simultaneously recorded. It showed itself to be only slightly influenced by the resting heart rate. The mentioned relationship of the systolic upstroke time of the ACG to internal isovolumic indexes of myocardial function makes this noninvasive measurable parameter an additional excellent tool for the evaluation of the left myocardial state, thus supporting a new aspect of the value of quantitative apexcardiography."} {"id": "PMID:1274824", "title": "\"New\" treatment for chronic intractable congestive heart failure.", "content": "The use of hexamethonium injected intravenously in successive 2.5 mg. doses resulted in alpha-adrenergic sympathetic nerve blocking and associated peripheral vasodilation with dramatic improvement of the symptoms and signs in patients with marked chronic intractable CHF. The vasodilatating effect of the drug is simple to monitor at the bedside and serves as an effective, simple means to \"bleed\" the patient intravenously by decreasing systemic venous tone and reducing the wall stress in the vessels. This intravenous \"bleeding\" results in a shifting of excessive blood from the lungs and central systemic venous areas to the larger volume of the more peripheral systemic venous reservoirs. Rheoplethysmorgraphic recordings of digital blood flow in the fingertips of the patients revealed marked constriction of all vessels of the fingers during CHF. Hexamethonium dilated all these vessels and increased digital blood flow even though arterial blood pressure was reduced by the drug. Theoretic discussions of aspects of the mechanism of congestive heart failure of the two-pump system of the heart of man and the mechanical or hemodynamic advantages of the small veins over the larger centrally located veins tend to explain why the use of hexamethonium benefits the circulation by producing vendoilatation. These studies indicate the therapeutic usefulness of hexamethonium in the management of acute and chronic intractable CHF and provides physiologic and theoretic data to explain why the drug is effective.", "contents": "\"New\" treatment for chronic intractable congestive heart failure. The use of hexamethonium injected intravenously in successive 2.5 mg. doses resulted in alpha-adrenergic sympathetic nerve blocking and associated peripheral vasodilation with dramatic improvement of the symptoms and signs in patients with marked chronic intractable CHF. The vasodilatating effect of the drug is simple to monitor at the bedside and serves as an effective, simple means to \"bleed\" the patient intravenously by decreasing systemic venous tone and reducing the wall stress in the vessels. This intravenous \"bleeding\" results in a shifting of excessive blood from the lungs and central systemic venous areas to the larger volume of the more peripheral systemic venous reservoirs. Rheoplethysmorgraphic recordings of digital blood flow in the fingertips of the patients revealed marked constriction of all vessels of the fingers during CHF. Hexamethonium dilated all these vessels and increased digital blood flow even though arterial blood pressure was reduced by the drug. Theoretic discussions of aspects of the mechanism of congestive heart failure of the two-pump system of the heart of man and the mechanical or hemodynamic advantages of the small veins over the larger centrally located veins tend to explain why the use of hexamethonium benefits the circulation by producing vendoilatation. These studies indicate the therapeutic usefulness of hexamethonium in the management of acute and chronic intractable CHF and provides physiologic and theoretic data to explain why the drug is effective."} {"id": "PMID:1274825", "title": "Therapeutic implications of diazepam in patients with elevated left ventricular filling pressure.", "content": "Diazepam (0.1 mg. per kilogram) was given intravenously to 12 patients with hemodynamic left ventricular failure at the time of cardiac catheterization. Anxiety was effectively relieved in 10 patients. Systemic and coronary hemodynamic parameters were assessed before and 5 and 15 minutes after diazepam. Heart rate, cardiac index, and left ventricular stroke-work index did not change significantly. Mean aortic pressure decreased in all patients (average of 10 mm. Hg) and left ventricular end-diastolic pressure (LVEDP) decreased from a mean +/- S.E.M. of 24.3 +/- 3 mm. Hg at rest to 16 +/- 2.1 at 5 minutes (p less than 0.001) and 15.8 +/- 2.1 at 5 minutes (p less than 0.002). Left ventricular angiography performed 30 minutes after diazepam did not increase LVEDP above the pre-diazepam control value. Systolic ejection period and tension-time index also decreased significantly after diazepam. Coronary hemodynamics and myocardial metabolism were unaltered by diazepam. The fall in LVEDP induced by diazepam is probably secondary to a decrease in arterial pressure (afterload) possibly associated with a decrease in venous return (preload). Our data therefore suggest that diazepam exerts a beneficial action on depressed left ventricular function and, thus, may be a sedative agent of choice in patients with myocardial infarction and heart failure.", "contents": "Therapeutic implications of diazepam in patients with elevated left ventricular filling pressure. Diazepam (0.1 mg. per kilogram) was given intravenously to 12 patients with hemodynamic left ventricular failure at the time of cardiac catheterization. Anxiety was effectively relieved in 10 patients. Systemic and coronary hemodynamic parameters were assessed before and 5 and 15 minutes after diazepam. Heart rate, cardiac index, and left ventricular stroke-work index did not change significantly. Mean aortic pressure decreased in all patients (average of 10 mm. Hg) and left ventricular end-diastolic pressure (LVEDP) decreased from a mean +/- S.E.M. of 24.3 +/- 3 mm. Hg at rest to 16 +/- 2.1 at 5 minutes (p less than 0.001) and 15.8 +/- 2.1 at 5 minutes (p less than 0.002). Left ventricular angiography performed 30 minutes after diazepam did not increase LVEDP above the pre-diazepam control value. Systolic ejection period and tension-time index also decreased significantly after diazepam. Coronary hemodynamics and myocardial metabolism were unaltered by diazepam. The fall in LVEDP induced by diazepam is probably secondary to a decrease in arterial pressure (afterload) possibly associated with a decrease in venous return (preload). Our data therefore suggest that diazepam exerts a beneficial action on depressed left ventricular function and, thus, may be a sedative agent of choice in patients with myocardial infarction and heart failure."} {"id": "PMID:1274826", "title": "Improved sinus node sensing after atropine.", "content": "Although atropine is known to increase sinus rate through its vagolytic effect, the effects of atropine on sinus node sensing are unknown. The purpose of this study was to investigate alterations in sinus node sensing produced by atropine. Measurement of the zone of sinus node reset and sinoatrial conduction time was performed in 10 patients by programmed premature atrial stimulation. The zone of sinus node reset was determined as the transition point where premature atrial stimuli were followed by a less than compensatory pause. Sinoatrial conduction time was calculated from sinus node return cycles in the area where sinus node reset occurred. Atropine administration produced a significant increase in the percentage of the sinus cycle length at which premature atrial contractions penetrated and reset the sinus node. Sinus node reset occurred at a mean percentage of the sinus cycle of 71 +/- 8 per cent before atropine and 83 +/- 5 per cent after atropine (P less 0.01). The sinoatrial conduction time was significantly reduced from 109 +/- 29 to 62 +/- 23 msec. (P less than 0.01) from atropine as sinus cycle length was reduced from 909 +/- 118 to 642 +/- 75 msec. after atropine. Sinus node echoes were observed in two patients. In one patient atropine abolished the appearance of sinus node echoes. In the second patient atropine reduced the coupling interval necessary to produce sinus node echoes but appeared to facilitate sinus node re-entry by the appearance of an additional sinus node echo and a reduction in the echo cycle length. This study demonstrates that atropine produces significant improvement of sinus node sensing in man.", "contents": "Improved sinus node sensing after atropine. Although atropine is known to increase sinus rate through its vagolytic effect, the effects of atropine on sinus node sensing are unknown. The purpose of this study was to investigate alterations in sinus node sensing produced by atropine. Measurement of the zone of sinus node reset and sinoatrial conduction time was performed in 10 patients by programmed premature atrial stimulation. The zone of sinus node reset was determined as the transition point where premature atrial stimuli were followed by a less than compensatory pause. Sinoatrial conduction time was calculated from sinus node return cycles in the area where sinus node reset occurred. Atropine administration produced a significant increase in the percentage of the sinus cycle length at which premature atrial contractions penetrated and reset the sinus node. Sinus node reset occurred at a mean percentage of the sinus cycle of 71 +/- 8 per cent before atropine and 83 +/- 5 per cent after atropine (P less 0.01). The sinoatrial conduction time was significantly reduced from 109 +/- 29 to 62 +/- 23 msec. (P less than 0.01) from atropine as sinus cycle length was reduced from 909 +/- 118 to 642 +/- 75 msec. after atropine. Sinus node echoes were observed in two patients. In one patient atropine abolished the appearance of sinus node echoes. In the second patient atropine reduced the coupling interval necessary to produce sinus node echoes but appeared to facilitate sinus node re-entry by the appearance of an additional sinus node echo and a reduction in the echo cycle length. This study demonstrates that atropine produces significant improvement of sinus node sensing in man."} {"id": "PMID:1274827", "title": "Residual effects when chronic propranolol therapy is discontinued within 48 hours of cardiopulmonary bypass.", "content": "Recommendations regarding the safe waiting period between discontinuing chronic oral propranolol therapy and beginning cardiopulmonary bypass have varied from a few hours to 2 weeks. In the present study, utilizing adult dogs, propranolol was discontinued 8 or 48 hours prior to surgery. A reduction in cardiac output and elevations of left ventricular end-diastolic pressure, peak systolic pressure, and systemic resistance were noted when cardiac function was evaluated following the induction of anesthesia and prior to undertaking cardiopulmonary bypass. The magnitude of these differences was directly related to the degree of volume loading and inversely related to the interval between the last dose of propranol and the determination of cardiac function. Reduction of heart rate was the most evanescent of propranolol's hemodynamic effects as the marked bradycardia which persisted throughout the course of propranolol therapy was no longer evident 8 hours after the last oral dose of the drug. Following total cardiopulmonary bypass of 1 hour's duration, undertaken 8 hours after the last oral dose of propranolol, cardiac output and left ventricular end-diastolic pressure had returned to normal but peak systolic pressure and systemic resistance remained significantly elevated, When 48 hours had elapsed between discontinuing propranolol and beginning cardiopulmonary bypass, postbypass cardiac function was essentially normal with only slight persistent elevations of peak systolic pressure and systemic resistance detected. When the combined effects of ischemic heart disease and propranolol therapy, the altered metabolic and hemodynamic effects of different routes of drug administration, and the varying durations of cardiopulmonary bypass are taken into consideration, some of the discrepancies between previously reported clinical and experimental findings regarding the duration of persistent propranolol effects can be understood. The clinical course is usually benign in patients who have received propranolol to within a few hours of surgery without specific indication. However, it is often complicated when the drug is continued until just prior to surgery in patients dependant on propranolol for pain or arrhythmia control. In patients demonstrating propranolol dependence, control of symptoms with intra-aortic balloon counterpulsation is recommended followed by the gradual withdrawal of propranolol and elective aortocoronary bypass surgery.", "contents": "Residual effects when chronic propranolol therapy is discontinued within 48 hours of cardiopulmonary bypass. Recommendations regarding the safe waiting period between discontinuing chronic oral propranolol therapy and beginning cardiopulmonary bypass have varied from a few hours to 2 weeks. In the present study, utilizing adult dogs, propranolol was discontinued 8 or 48 hours prior to surgery. A reduction in cardiac output and elevations of left ventricular end-diastolic pressure, peak systolic pressure, and systemic resistance were noted when cardiac function was evaluated following the induction of anesthesia and prior to undertaking cardiopulmonary bypass. The magnitude of these differences was directly related to the degree of volume loading and inversely related to the interval between the last dose of propranol and the determination of cardiac function. Reduction of heart rate was the most evanescent of propranolol's hemodynamic effects as the marked bradycardia which persisted throughout the course of propranolol therapy was no longer evident 8 hours after the last oral dose of the drug. Following total cardiopulmonary bypass of 1 hour's duration, undertaken 8 hours after the last oral dose of propranolol, cardiac output and left ventricular end-diastolic pressure had returned to normal but peak systolic pressure and systemic resistance remained significantly elevated, When 48 hours had elapsed between discontinuing propranolol and beginning cardiopulmonary bypass, postbypass cardiac function was essentially normal with only slight persistent elevations of peak systolic pressure and systemic resistance detected. When the combined effects of ischemic heart disease and propranolol therapy, the altered metabolic and hemodynamic effects of different routes of drug administration, and the varying durations of cardiopulmonary bypass are taken into consideration, some of the discrepancies between previously reported clinical and experimental findings regarding the duration of persistent propranolol effects can be understood. The clinical course is usually benign in patients who have received propranolol to within a few hours of surgery without specific indication. However, it is often complicated when the drug is continued until just prior to surgery in patients dependant on propranolol for pain or arrhythmia control. In patients demonstrating propranolol dependence, control of symptoms with intra-aortic balloon counterpulsation is recommended followed by the gradual withdrawal of propranolol and elective aortocoronary bypass surgery."} {"id": "PMID:1274828", "title": "Attacks of ventricular fibrillation and unconsciousness in a patient with prolonged QT interval. A family study.", "content": "A syndrome previously recognized by Romano and Ward is characterized by prolonged QT interval on the ECG, and spells of unconsciousness. The case of a patient is reported with successive ECG recordings during the attacks; ventricular flutter and multifocal ventricular tachycardia were noted, with rapid spontaneous recovery and relapse. Cases of stillbirth and sudden death in infancy among the siblings, together with QT interval tachycardia were noted, with rapid spontaneous recovery and relapse. Cases of stillbirth and sudden death ininfancy among the siblings, together with QT interval prolongation in the relatives point to an autosomal dominant transmission, with the propositus being apparently homozygous. The chromosomes of the patient are normal. The attacks were controlled by the association of propranolol and digitalis which seems to be the optimal long-term therapy in such cases. In view of the poor prognosis in untreated cases, and the good results of a correct therapy, an ECG should be recorded at rest and after exercise in all children suffering from spells of unconsciousness.", "contents": "Attacks of ventricular fibrillation and unconsciousness in a patient with prolonged QT interval. A family study. A syndrome previously recognized by Romano and Ward is characterized by prolonged QT interval on the ECG, and spells of unconsciousness. The case of a patient is reported with successive ECG recordings during the attacks; ventricular flutter and multifocal ventricular tachycardia were noted, with rapid spontaneous recovery and relapse. Cases of stillbirth and sudden death in infancy among the siblings, together with QT interval tachycardia were noted, with rapid spontaneous recovery and relapse. Cases of stillbirth and sudden death ininfancy among the siblings, together with QT interval prolongation in the relatives point to an autosomal dominant transmission, with the propositus being apparently homozygous. The chromosomes of the patient are normal. The attacks were controlled by the association of propranolol and digitalis which seems to be the optimal long-term therapy in such cases. In view of the poor prognosis in untreated cases, and the good results of a correct therapy, an ECG should be recorded at rest and after exercise in all children suffering from spells of unconsciousness."} {"id": "PMID:1274839", "title": "Particle size distribution and chemical composition of coal-tar fumes.", "content": "The study was intended to characterize the chemical and physical nature of coal-tar fumes emitted from spreading applications of coal tar. Two separate experiments were performed. The first resulted in the determination of a coal-tar fume particle size distribution. The second experiment resulted in the identification of the primary compounds found in collected tar fumes and a determination of their relative concentration.", "contents": "Particle size distribution and chemical composition of coal-tar fumes. The study was intended to characterize the chemical and physical nature of coal-tar fumes emitted from spreading applications of coal tar. Two separate experiments were performed. The first resulted in the determination of a coal-tar fume particle size distribution. The second experiment resulted in the identification of the primary compounds found in collected tar fumes and a determination of their relative concentration."} {"id": "PMID:1274840", "title": "Respirator cartridge efficiency studies: VI. Effect of concentration.", "content": "The service life of organic vapor cartridges was determined for ten vapors at concentrations between 50 and 3000 ppm. The breakthrough time (tb) conformed to the empirical expression tb = aCf, where C is the concentration in ppm and a and be are constants. The average value for b at 10% breakthrough was -0.67 +/- 0.17. The service life is inversely proportional to flow rate for acetone and benzene.", "contents": "Respirator cartridge efficiency studies: VI. Effect of concentration. The service life of organic vapor cartridges was determined for ten vapors at concentrations between 50 and 3000 ppm. The breakthrough time (tb) conformed to the empirical expression tb = aCf, where C is the concentration in ppm and a and be are constants. The average value for b at 10% breakthrough was -0.67 +/- 0.17. The service life is inversely proportional to flow rate for acetone and benzene."} {"id": "PMID:1274841", "title": "Health hazards from oil, soot and metals at a hot forging operation.", "content": "An extensive study of a hot forging operation was performed to characterize and quantitate worker exposures to the aerosol formed by an oil-based die lubricant and it's decomposition products. Total particulate breathing zone levels up to 65 mg/m3 and benzo (a) pyrene levels up to 2.9 mug/m3 were measured.", "contents": "Health hazards from oil, soot and metals at a hot forging operation. An extensive study of a hot forging operation was performed to characterize and quantitate worker exposures to the aerosol formed by an oil-based die lubricant and it's decomposition products. Total particulate breathing zone levels up to 65 mg/m3 and benzo (a) pyrene levels up to 2.9 mug/m3 were measured."} {"id": "PMID:1274842", "title": "Investigation of sound level conversion as a means of rating ear protector performance.", "content": "Sound level conversion, a single-number measure describing the noise reduction afforded by ear protectors, was calculated for 30 ear protectors in 615 industrial noise spectra. The results vindicate the utility of this measure for situations in which the noise hazard is characterised only by C- and A-weighted sound levels. A simple procedure for calculating SLC, accurate within +/- 1dB, is proposed. Minor adjustments of the calculation procedure enable wearer protection rates in the range 50% to 97% to be achieved.", "contents": "Investigation of sound level conversion as a means of rating ear protector performance. Sound level conversion, a single-number measure describing the noise reduction afforded by ear protectors, was calculated for 30 ear protectors in 615 industrial noise spectra. The results vindicate the utility of this measure for situations in which the noise hazard is characterised only by C- and A-weighted sound levels. A simple procedure for calculating SLC, accurate within +/- 1dB, is proposed. Minor adjustments of the calculation procedure enable wearer protection rates in the range 50% to 97% to be achieved."} {"id": "PMID:1274852", "title": "Occupational aspects of passive smoking.", "content": "Peak carbon monoxide levels of 30 ppm were found during a work shift in a poorly ventilated tavern. A time-weighted average concentration of 17 ppm CO was found as well as elevated particulate levels. The occupational exposure to cigarette effluents is discussed in light of OSHA regulations.", "contents": "Occupational aspects of passive smoking. Peak carbon monoxide levels of 30 ppm were found during a work shift in a poorly ventilated tavern. A time-weighted average concentration of 17 ppm CO was found as well as elevated particulate levels. The occupational exposure to cigarette effluents is discussed in light of OSHA regulations."} {"id": "PMID:1274853", "title": "Gas chromatographic determination of acetic acid in industrial atmosphere and waste water.", "content": "A gas chromatographic (GC) method is presented for the specific determination of acetic acid in air and total ionic acetate (as acetic acid) in industrial waste water. Atmospheric air samples are collected in fritted midget bubblers containing aqueous sodium carbonate solution; wastewater samples are treated directly with sodium carbonate. Both air and water samples are concentrated by evaporation of water, and the acetic acid is regenerated by the addition of hydrochloric acid. The amount of acetic acid is determined quantitatively on a porous polymer packed column by internal standardization with propionic acid. GC conditions are described for the suppression of \"ghosting\" and \"tailing\" caused by adsorption phenomena associated with the GC behavior of organic acids.", "contents": "Gas chromatographic determination of acetic acid in industrial atmosphere and waste water. A gas chromatographic (GC) method is presented for the specific determination of acetic acid in air and total ionic acetate (as acetic acid) in industrial waste water. Atmospheric air samples are collected in fritted midget bubblers containing aqueous sodium carbonate solution; wastewater samples are treated directly with sodium carbonate. Both air and water samples are concentrated by evaporation of water, and the acetic acid is regenerated by the addition of hydrochloric acid. The amount of acetic acid is determined quantitatively on a porous polymer packed column by internal standardization with propionic acid. GC conditions are described for the suppression of \"ghosting\" and \"tailing\" caused by adsorption phenomena associated with the GC behavior of organic acids."} {"id": "PMID:1274854", "title": "The effect of general fatigue on isometric strength-endurance measurements and the electromyogram of the biceps brachii.", "content": "Contraction strength, endurance and the electromyogram of the biceps brachii were examined following treadmill exercise at 50 and 60% of maximum aerobic capacity. Exercise did not exert a significant influence on any of these parameters indicating they are relatively insensitive indicators of general fatigue.", "contents": "The effect of general fatigue on isometric strength-endurance measurements and the electromyogram of the biceps brachii. Contraction strength, endurance and the electromyogram of the biceps brachii were examined following treadmill exercise at 50 and 60% of maximum aerobic capacity. Exercise did not exert a significant influence on any of these parameters indicating they are relatively insensitive indicators of general fatigue."} {"id": "PMID:1274855", "title": "Respirator cartridge efficiency studies: VII. Effect of relative humidity and temperature.", "content": "Cartridge service life is not appreciably affected at relative humidities below 50%. However, performance is severely compromised when the humidity exceeds 65%. Experimental values are compared from those calculated from the adsorption isotherm, Mecklenburg and modified Wheeler equations. Calculations indicate that temperature does not play a significant role in service life predictions.", "contents": "Respirator cartridge efficiency studies: VII. Effect of relative humidity and temperature. Cartridge service life is not appreciably affected at relative humidities below 50%. However, performance is severely compromised when the humidity exceeds 65%. Experimental values are compared from those calculated from the adsorption isotherm, Mecklenburg and modified Wheeler equations. Calculations indicate that temperature does not play a significant role in service life predictions."} {"id": "PMID:1274856", "title": "A summary of the NIOSH evaluation program of portable direct-reading meters.", "content": "The National Institute for Occupation Safety and Health (NIOSH) has developed a program to evaluate portable, direct-reading instruments. The results of these evaluations for CO, SO2, combustible gas, and NO2 instruments are reported. Realistic performance specifications have been developed for each of these types of instruments.", "contents": "A summary of the NIOSH evaluation program of portable direct-reading meters. The National Institute for Occupation Safety and Health (NIOSH) has developed a program to evaluate portable, direct-reading instruments. The results of these evaluations for CO, SO2, combustible gas, and NO2 instruments are reported. Realistic performance specifications have been developed for each of these types of instruments."} {"id": "PMID:1274857", "title": "Characterization of talc and associated minerals.", "content": "The unequivocal identification of mineral impurities in talc requires definitive analytical techniques due to the very similar structure of many naturally occurring silicates and the small quantities of associated minerals frequently found. The instrumental methods and techniques extant for this purpose are reviewed. Light microscopy, x-ray diffractometry, and differential thermal analysis have been found to be particularly useful, complementary, and practical for both exploratory and routine determinations of mineral impurities in the talc matrix. When necessary, transmission electron microscopy is recommended for the analysis of mineral components present at sub-trace levels.", "contents": "Characterization of talc and associated minerals. The unequivocal identification of mineral impurities in talc requires definitive analytical techniques due to the very similar structure of many naturally occurring silicates and the small quantities of associated minerals frequently found. The instrumental methods and techniques extant for this purpose are reviewed. Light microscopy, x-ray diffractometry, and differential thermal analysis have been found to be particularly useful, complementary, and practical for both exploratory and routine determinations of mineral impurities in the talc matrix. When necessary, transmission electron microscopy is recommended for the analysis of mineral components present at sub-trace levels."} {"id": "PMID:1274858", "title": "In-home measurement of background particles and particulates and propellents produced by an air freshener.", "content": "When an aerosol product is dispensed into the atmosphere a mixture of particles and propellent gases is released. The potential exposures resulting from normal use were measured and compared to the background and the exposure of the healthy industrial worker. This model can serve as a guide for assessing use exposures of aerosol products.", "contents": "In-home measurement of background particles and particulates and propellents produced by an air freshener. When an aerosol product is dispensed into the atmosphere a mixture of particles and propellent gases is released. The potential exposures resulting from normal use were measured and compared to the background and the exposure of the healthy industrial worker. This model can serve as a guide for assessing use exposures of aerosol products."} {"id": "PMID:1274859", "title": "Improved hopcalite procedure for the determination of mercury vapor in air by flameless atomic absorption.", "content": "Mercury vapor is efficiently trapped from air by passage through a small glass tube filled with hopcalite. The hopcalite and adsorbed mercury are dissolved in a mixture of nitric and hydrochloric acids. Solution is rapid and complete, with no loss of mercury. Analysis is completed by flameless atomic absorption.", "contents": "Improved hopcalite procedure for the determination of mercury vapor in air by flameless atomic absorption. Mercury vapor is efficiently trapped from air by passage through a small glass tube filled with hopcalite. The hopcalite and adsorbed mercury are dissolved in a mixture of nitric and hydrochloric acids. Solution is rapid and complete, with no loss of mercury. Analysis is completed by flameless atomic absorption."} {"id": "PMID:1274860", "title": "Vacu-Samplers, a simple method for taking accurate quantitative gas and vapor samples using partially evacuated steel containers.", "content": "The Vacu-Sampler, a partially evacuated steel cylinder, has been widely used as a diagnostic industrial hygiene sampling system. This study examines the rational behind the Vacu-Sampler and two simple, quantitative procedures that can be used to obtain accurate sample results in ppm with gas chromatographic analysis.", "contents": "Vacu-Samplers, a simple method for taking accurate quantitative gas and vapor samples using partially evacuated steel containers. The Vacu-Sampler, a partially evacuated steel cylinder, has been widely used as a diagnostic industrial hygiene sampling system. This study examines the rational behind the Vacu-Sampler and two simple, quantitative procedures that can be used to obtain accurate sample results in ppm with gas chromatographic analysis."} {"id": "PMID:1274861", "title": "Impaired parasympathetic responses in patients after myocardial infarction.", "content": "To assess whether vagal and sympathetic responses are impaired 3 months after myocardial infarction, 27 patients, 15 age-matched control subjects and 13 young normal subjects underwent physiologic stress tests. In patients, facial immersion in water at 25 degrees and 0 degrees C provoked less slowing of heart rate than in age-matched control subjects. Young normal persons responded with the greatest reduction in heart rate. Response to facial immersion decreased linearly with age in normal subjects (Y = -0.97X+86). Isometric handgrip or cold pressor test elicited brisk increases in blood pressure in almost all patients, but the vagal response to facial immersion correlated poorly with such pressor responses. Thus, in the patients studied 3 months after myocardial infarction, the parasympathetic response to facial immersion was significantly impaired whereas sympathetic pressor responses remained intact.", "contents": "Impaired parasympathetic responses in patients after myocardial infarction. To assess whether vagal and sympathetic responses are impaired 3 months after myocardial infarction, 27 patients, 15 age-matched control subjects and 13 young normal subjects underwent physiologic stress tests. In patients, facial immersion in water at 25 degrees and 0 degrees C provoked less slowing of heart rate than in age-matched control subjects. Young normal persons responded with the greatest reduction in heart rate. Response to facial immersion decreased linearly with age in normal subjects (Y = -0.97X+86). Isometric handgrip or cold pressor test elicited brisk increases in blood pressure in almost all patients, but the vagal response to facial immersion correlated poorly with such pressor responses. Thus, in the patients studied 3 months after myocardial infarction, the parasympathetic response to facial immersion was significantly impaired whereas sympathetic pressor responses remained intact."} {"id": "PMID:1274862", "title": "Pacemaker failures characterized by continuous direct current leakage.", "content": "Pulse generator failure caused by continuous leakage of direct current through an output capacitor has not previously been appreciated. Routine post-explant electronic evaluation has identified the defect in six implanted and one external pulse generator. The constant direct current in the implantable units, 0.14 to 0.26 milliamperes, is in the range that produces ventricular arrhythmias in dogs although this did not occur in our patients. Evidence of local myocardial damage existed in four cases and of electrode deterioration in three. The implant failures occurred without warning and in four cases within 2 weeks of demonstrated normal function, blunting the predictive benefits of pacemaker monitoring programs. Capacitor discharge circuits used in many pacers are inherently capable of developing direct current leakage in the event of output capacitor short circuit. In one model of pacemakers such continuous direct current leakage caused 8.3 percent (3 of 36) of pulse generator failures, widely scattered in time at 23, 27 and 46 months after implant. Capacitor short circuit causing constant direct current leakage can masquerade as primary battery failure and should be suspected when cessation of pacer function is associated with increased threshold or poor myocardial electrogram without evidence of wire break or displacement.", "contents": "Pacemaker failures characterized by continuous direct current leakage. Pulse generator failure caused by continuous leakage of direct current through an output capacitor has not previously been appreciated. Routine post-explant electronic evaluation has identified the defect in six implanted and one external pulse generator. The constant direct current in the implantable units, 0.14 to 0.26 milliamperes, is in the range that produces ventricular arrhythmias in dogs although this did not occur in our patients. Evidence of local myocardial damage existed in four cases and of electrode deterioration in three. The implant failures occurred without warning and in four cases within 2 weeks of demonstrated normal function, blunting the predictive benefits of pacemaker monitoring programs. Capacitor discharge circuits used in many pacers are inherently capable of developing direct current leakage in the event of output capacitor short circuit. In one model of pacemakers such continuous direct current leakage caused 8.3 percent (3 of 36) of pulse generator failures, widely scattered in time at 23, 27 and 46 months after implant. Capacitor short circuit causing constant direct current leakage can masquerade as primary battery failure and should be suspected when cessation of pacer function is associated with increased threshold or poor myocardial electrogram without evidence of wire break or displacement."} {"id": "PMID:1274864", "title": "Effects of unilateral cardiac sympathetic denervation on the ventricular fibrillation threshold.", "content": "A train of gated stimuli scanning the entire vulnerable period was delivered to the right anterior or left posterior ventricular surface to study the ventricular fibrillation threshold in anesthetized and vagotomized dogs. Heart rate was held constant by atrial pacing. Measurements were obtained in control conditions and after surgical removal of one stellate ganglion. To avoid the shortcomings associated with an irreversible procedure like stellectomy, control fibrillation threshold measurements were also alternated with determinations during reversible blockade by cooling of one stellate ganglion. The results were similar with both techniques. In nine animals, ablation or cooling of the left stellate ganglion increased ventricular fibrillation threshold by 72 +/- 35 (mean +/- standard deviation) percent compared with control values (P less than 0.001). By contrast, in 11 animals, ablation or cooling of the right stellate ganglion lowered the threshold by 48 +/- 14 percent compared with control values (P less than 0.001). Electrode location did not influence the results. The observed changes depended solely upon unilateral removal of cardiac sympathetic activity and were not demonstrable if such activity was low. These results suggest that right and left cardiac sympathetic nerves may have different and specific effects on cardiac excitability. They also contribute to the understanding of the pathogenesis of the long Q-T syndrome (characterized by episodes of ventricular fibrillation associated with increased sympathetic activity) and increase the rationale for left stellectomy as the specific treatment for this illness. Left stellectomy, by raising the ventricular fibrillation threshold, may also represent an alternative measure in patients at high risk of sudden death from ventricular arrhythmias resistant to medical therapy.", "contents": "Effects of unilateral cardiac sympathetic denervation on the ventricular fibrillation threshold. A train of gated stimuli scanning the entire vulnerable period was delivered to the right anterior or left posterior ventricular surface to study the ventricular fibrillation threshold in anesthetized and vagotomized dogs. Heart rate was held constant by atrial pacing. Measurements were obtained in control conditions and after surgical removal of one stellate ganglion. To avoid the shortcomings associated with an irreversible procedure like stellectomy, control fibrillation threshold measurements were also alternated with determinations during reversible blockade by cooling of one stellate ganglion. The results were similar with both techniques. In nine animals, ablation or cooling of the left stellate ganglion increased ventricular fibrillation threshold by 72 +/- 35 (mean +/- standard deviation) percent compared with control values (P less than 0.001). By contrast, in 11 animals, ablation or cooling of the right stellate ganglion lowered the threshold by 48 +/- 14 percent compared with control values (P less than 0.001). Electrode location did not influence the results. The observed changes depended solely upon unilateral removal of cardiac sympathetic activity and were not demonstrable if such activity was low. These results suggest that right and left cardiac sympathetic nerves may have different and specific effects on cardiac excitability. They also contribute to the understanding of the pathogenesis of the long Q-T syndrome (characterized by episodes of ventricular fibrillation associated with increased sympathetic activity) and increase the rationale for left stellectomy as the specific treatment for this illness. Left stellectomy, by raising the ventricular fibrillation threshold, may also represent an alternative measure in patients at high risk of sudden death from ventricular arrhythmias resistant to medical therapy."} {"id": "PMID:1274865", "title": "Activation of left ventricular receptors with nonmedullated vagal afferent fibers during occlusion of a coronary artery in the cat.", "content": "Studies were made of the effects of temporary occlusion of a coronary artery on the activity of nonmedullated afferent vagal fibers from the left ventricle of 15 cats. Recordings were made from 14 single fibers and 4 filaments with 2 to 3 fibers dissected from the right vagus. Their normal activity averaged 1.8 impulses/sec, and they were identified by an increase in activity to 4 to 17 impulses/sec during a brief occlusion of the aorta and by a conduction velocity of 0.6 to 1.3 m/sec (mean 0.9). The receptors studied were distributed throughout the ventricle, as determined by mechanical probing of the nonbeating heart at the end of the experiments. With a 1 to 1.5 minute occlusion of a coronary artery, the activity of receptors within the area supplied by that artery increased in concert with the systolic bulging of the ischemic area. The initial increase in activity occurred during systole, suggesting that the receptors were activated mechanically rather than by chemical changes in the ischemic zone. The activity soon became continuous, reaching a maximum of 15.4 impulses/sec (mean value). The maximal activity was not sustained; during occlusion of up to 40 minutes it decreased to 5 impulses/sec (mean value after 5 to 10 minutes. The decrease may result from anoxia since three of four tested receptors showed an increase in activity after release of occlusion.", "contents": "Activation of left ventricular receptors with nonmedullated vagal afferent fibers during occlusion of a coronary artery in the cat. Studies were made of the effects of temporary occlusion of a coronary artery on the activity of nonmedullated afferent vagal fibers from the left ventricle of 15 cats. Recordings were made from 14 single fibers and 4 filaments with 2 to 3 fibers dissected from the right vagus. Their normal activity averaged 1.8 impulses/sec, and they were identified by an increase in activity to 4 to 17 impulses/sec during a brief occlusion of the aorta and by a conduction velocity of 0.6 to 1.3 m/sec (mean 0.9). The receptors studied were distributed throughout the ventricle, as determined by mechanical probing of the nonbeating heart at the end of the experiments. With a 1 to 1.5 minute occlusion of a coronary artery, the activity of receptors within the area supplied by that artery increased in concert with the systolic bulging of the ischemic area. The initial increase in activity occurred during systole, suggesting that the receptors were activated mechanically rather than by chemical changes in the ischemic zone. The activity soon became continuous, reaching a maximum of 15.4 impulses/sec (mean value). The maximal activity was not sustained; during occlusion of up to 40 minutes it decreased to 5 impulses/sec (mean value after 5 to 10 minutes. The decrease may result from anoxia since three of four tested receptors showed an increase in activity after release of occlusion."} {"id": "PMID:1274866", "title": "Automated precordial mapping for S-T segment analysis: variability in serial mappings of normal subjects and patients with stable S-T elevation.", "content": "An automated method of precordial mapping using a modified Caceres U.S. Public Health Service Electrocardiogram Diagnosing Program has been developed. The S-T segment elevation was measured in three successive complexes and averaged for each of the 35 precordial leads. The onset of the S-T segment (J point) was accurately located in over 99 percent of instances. The time required to sample the 35 leads averaged 8 1/2 minutes with subsequent data analysis requiring an additional 7 minutes. The S-T segment variability between serial mappings done over a 1 to 2 hour period was determined in normal subjects and patients with stable S-T elevation. The average S-T segment elevation/35 leads in normal subjects was 1.28 mv (range 0.41 to 2.14) and the between-mapping variability was +/- 0.25 mv at the 95 percent confidence level. The average S-T segment elevation/35 leads in the patients was 4.01 mv (range 1.35 to 7.28) mv. The between-mapping variability was +/- 0.29 mv (95 percent confidence level), and was not statistically different from the variability in normal subjects (P less than 0.05).", "contents": "Automated precordial mapping for S-T segment analysis: variability in serial mappings of normal subjects and patients with stable S-T elevation. An automated method of precordial mapping using a modified Caceres U.S. Public Health Service Electrocardiogram Diagnosing Program has been developed. The S-T segment elevation was measured in three successive complexes and averaged for each of the 35 precordial leads. The onset of the S-T segment (J point) was accurately located in over 99 percent of instances. The time required to sample the 35 leads averaged 8 1/2 minutes with subsequent data analysis requiring an additional 7 minutes. The S-T segment variability between serial mappings done over a 1 to 2 hour period was determined in normal subjects and patients with stable S-T elevation. The average S-T segment elevation/35 leads in normal subjects was 1.28 mv (range 0.41 to 2.14) and the between-mapping variability was +/- 0.25 mv at the 95 percent confidence level. The average S-T segment elevation/35 leads in the patients was 4.01 mv (range 1.35 to 7.28) mv. The between-mapping variability was +/- 0.29 mv (95 percent confidence level), and was not statistically different from the variability in normal subjects (P less than 0.05)."} {"id": "PMID:1274867", "title": "Normalized first derivative ofthe left apex cardiogram in assessment of left ventricular function.", "content": "The relation between the left displacement apex cardiogram and the left ventricular pressure during isovolumic contraction was studied in 30 patients with cardiac disease. Using the instantaneous relation between the first time derivative and the magnitude of both the left apex cardiogram and the left ventricular pressure, normalized derivatives were obtained. These noramized velocities were correlated with each other and with several indexes of left ventricular function. The normalized derivatives of the left apex cardiogram (dD/dt/D) and the left ventricular pressure (dP/dt/P) were similar in magnitude, standard deviation and variation coefficient. No such similarity was present when the first time derivatives of each tracing (dD/dt and dP/dt) were compared. A highly significant relation was found between normalized displacement velocity and normalized pressure velocity using both total (r = 0.76, P less than 0.001) and developed (r = 0.75, P less than 0.001) displacement and pressure. Significant correlations with several other indexes of left ventricular function (end-diastolic pressure, peak dP/dt, maximal velocity of the contractile elements at zero load[Vmax]) were also observed. It is concluded that the index dD/dt/D of the left apex cardiogram is an important noninvasive tool for assessing left ventricular function in man.", "contents": "Normalized first derivative ofthe left apex cardiogram in assessment of left ventricular function. The relation between the left displacement apex cardiogram and the left ventricular pressure during isovolumic contraction was studied in 30 patients with cardiac disease. Using the instantaneous relation between the first time derivative and the magnitude of both the left apex cardiogram and the left ventricular pressure, normalized derivatives were obtained. These noramized velocities were correlated with each other and with several indexes of left ventricular function. The normalized derivatives of the left apex cardiogram (dD/dt/D) and the left ventricular pressure (dP/dt/P) were similar in magnitude, standard deviation and variation coefficient. No such similarity was present when the first time derivatives of each tracing (dD/dt and dP/dt) were compared. A highly significant relation was found between normalized displacement velocity and normalized pressure velocity using both total (r = 0.76, P less than 0.001) and developed (r = 0.75, P less than 0.001) displacement and pressure. Significant correlations with several other indexes of left ventricular function (end-diastolic pressure, peak dP/dt, maximal velocity of the contractile elements at zero load[Vmax]) were also observed. It is concluded that the index dD/dt/D of the left apex cardiogram is an important noninvasive tool for assessing left ventricular function in man."} {"id": "PMID:1274868", "title": "Renal arterial stenosis and hypertension. II. Current criteria for surgery.", "content": "Criteria developed from a previously reported study in 1969 concerning outcome of renal arterial surgery were applied over the next 5 years (1967 through 1971) to a group of 33 patients from a total of 121 with renal arterial stenosis. After demonstration of ischemia of the involved kidney, surgery was performed only when the degree of atherosclerotic disease and complications were minimal. With this selective process the incidence rate of significant postoperative improvement was raised from 26 to 75 percent and was maintained at 60 percent through the end of 1973, the mortality rate decreasing from 35 to less than 10 percent. The data indicate that medical therapy is the initial treatment of choice in patients over 50 to 55 years of age who have atherosclerotic disease but that the outcome of surgery can be satisfactory in properly selected younger patients.", "contents": "Renal arterial stenosis and hypertension. II. Current criteria for surgery. Criteria developed from a previously reported study in 1969 concerning outcome of renal arterial surgery were applied over the next 5 years (1967 through 1971) to a group of 33 patients from a total of 121 with renal arterial stenosis. After demonstration of ischemia of the involved kidney, surgery was performed only when the degree of atherosclerotic disease and complications were minimal. With this selective process the incidence rate of significant postoperative improvement was raised from 26 to 75 percent and was maintained at 60 percent through the end of 1973, the mortality rate decreasing from 35 to less than 10 percent. The data indicate that medical therapy is the initial treatment of choice in patients over 50 to 55 years of age who have atherosclerotic disease but that the outcome of surgery can be satisfactory in properly selected younger patients."} {"id": "PMID:1274871", "title": "Noninvasive diagnosis of a false left ventricular aneurysm with radioisotope gated cardiac blood pool imaging. Differentiation from true aneurysm.", "content": "Unlike the true left ventricular aneurysm, false aneurysms have recently been shown to be subject to late rupture. Rarely diagnosed before surgery or autopsy, the false aneurysm has never been identified by noninvasive techniques. We report the first such noninvasive diagnosis employing radioisotope gated cardiac blood pool imaging. Due to the unique and possibly life-threatening clinical course and potential for surgical cure of false left ventricular aneurysm, early noninvasive diagnosis by imaging techniques may be critical. The methods shown here are generally applicable, becoming widely available and may help in evaluation of false left ventricular aneurysm as a cause of sudden death.", "contents": "Noninvasive diagnosis of a false left ventricular aneurysm with radioisotope gated cardiac blood pool imaging. Differentiation from true aneurysm. Unlike the true left ventricular aneurysm, false aneurysms have recently been shown to be subject to late rupture. Rarely diagnosed before surgery or autopsy, the false aneurysm has never been identified by noninvasive techniques. We report the first such noninvasive diagnosis employing radioisotope gated cardiac blood pool imaging. Due to the unique and possibly life-threatening clinical course and potential for surgical cure of false left ventricular aneurysm, early noninvasive diagnosis by imaging techniques may be critical. The methods shown here are generally applicable, becoming widely available and may help in evaluation of false left ventricular aneurysm as a cause of sudden death."} {"id": "PMID:1274872", "title": "Wolff-Parkinson-White syndrome with 1:2 atrioventricular conduction.", "content": "The QRS complex of the Wolff-Parkinson-White syndrome is thought to represent a fusion beat resulting from conduction over the normal pathway and an anomalous pathway. This report demonstrates utilization of both of these pathways resulting in two ventricular responses from a single supraventricular impulse. The presence of \"1:2\" atrioventricular conduction in this case firmly supports the fusion beat theory of the Wolff-Parkinson-White syndrome.", "contents": "Wolff-Parkinson-White syndrome with 1:2 atrioventricular conduction. The QRS complex of the Wolff-Parkinson-White syndrome is thought to represent a fusion beat resulting from conduction over the normal pathway and an anomalous pathway. This report demonstrates utilization of both of these pathways resulting in two ventricular responses from a single supraventricular impulse. The presence of \"1:2\" atrioventricular conduction in this case firmly supports the fusion beat theory of the Wolff-Parkinson-White syndrome."} {"id": "PMID:1274873", "title": "Multiple aortic aneurysms in relapsing polychondritis.", "content": "A patient with relapsing polychondritis and thoracic and abdominal aortic aneurysms is described. The aortic changes were due to aortitis, which primarily involved the media, with increased vascularization, perviascular infiltration of mononuclear cells, increased amounts of collagen and decreased amounts of elastic tissue and sulfated acid mucopolysaccharides. Aortic aneurysms frequently occur in relapsing polychondritis; they are usually in the ascending aorta but may be multiple and involve the abdominal aorta; involvement of the ascending aorta results in aortic regurgitation and left ventricular failure, and involvement of the abdominal aorta may be clinically silent and result in fatal rupture.", "contents": "Multiple aortic aneurysms in relapsing polychondritis. A patient with relapsing polychondritis and thoracic and abdominal aortic aneurysms is described. The aortic changes were due to aortitis, which primarily involved the media, with increased vascularization, perviascular infiltration of mononuclear cells, increased amounts of collagen and decreased amounts of elastic tissue and sulfated acid mucopolysaccharides. Aortic aneurysms frequently occur in relapsing polychondritis; they are usually in the ascending aorta but may be multiple and involve the abdominal aorta; involvement of the ascending aorta results in aortic regurgitation and left ventricular failure, and involvement of the abdominal aorta may be clinically silent and result in fatal rupture."} {"id": "PMID:1274885", "title": "The effects of sweat nitrogen losses in evaluating protein utilization by preadolescent children.", "content": "A nitrogen balance study was conducted to determine the effects of three levels of nitrogen intake on the loss of nitrogen through sweat and to assess further the impact of sweat nitrogen on protein needs of preadolescent children. Values were determined through the collection of 24-hr, total body sweat samples from twelve healthy boys having a mean age of 8 years, 8 months. Mean height and weight of the subjects were 131.4 cm and 31.0 kg, respectively. Environmental conditions were relatively constant during the study. Mean sweat nitrogen losses were 208, 287, and 368 mg/day on daily protein intakes of 29, 54, and 84 g, respectively. Mean nitrogen balances per day were 0.39, 0.09, and 1.95 g when sweat nitrogen losses were included in the calculations. At the lower and moderate levels of protein intake, nine and six subjects were in negative nitrogen balance when sweat losses were considered. Sweat nitrogen losses in the boys were similar to a previous study with preadolescent girls. Based upon published basal metabolic rates and mean sweat nitrogen losses of 261 and 288 mg/day for girls and boys, the nitrogen lost through sweat was 0.25 mg/basal kcal for both sexes. An estimation of 0.5 mg/basal kcal for integumental nitrogen loss appears realistic for this age group.", "contents": "The effects of sweat nitrogen losses in evaluating protein utilization by preadolescent children. A nitrogen balance study was conducted to determine the effects of three levels of nitrogen intake on the loss of nitrogen through sweat and to assess further the impact of sweat nitrogen on protein needs of preadolescent children. Values were determined through the collection of 24-hr, total body sweat samples from twelve healthy boys having a mean age of 8 years, 8 months. Mean height and weight of the subjects were 131.4 cm and 31.0 kg, respectively. Environmental conditions were relatively constant during the study. Mean sweat nitrogen losses were 208, 287, and 368 mg/day on daily protein intakes of 29, 54, and 84 g, respectively. Mean nitrogen balances per day were 0.39, 0.09, and 1.95 g when sweat nitrogen losses were included in the calculations. At the lower and moderate levels of protein intake, nine and six subjects were in negative nitrogen balance when sweat losses were considered. Sweat nitrogen losses in the boys were similar to a previous study with preadolescent girls. Based upon published basal metabolic rates and mean sweat nitrogen losses of 261 and 288 mg/day for girls and boys, the nitrogen lost through sweat was 0.25 mg/basal kcal for both sexes. An estimation of 0.5 mg/basal kcal for integumental nitrogen loss appears realistic for this age group."} {"id": "PMID:1274886", "title": "Personality characteristics in obesity: relation of MMPI profile and age of onset of obesity to success in weight reduction.", "content": "A group of 142 obese subjects was seen in an obesity clinic over a 2-year period. Of these, 116 had assessment of personality factors by the Minnesota Multiphasic Personality Inventory (MMPI), and 71 were followed for periods of 4 to 28 months in order to determine success at weight reduction by means of a conventional dietary regimen. The MMPI profiles of the obese subjects were compared to those of a general medical population of 50,000 patients seen in the Department of Internal Medicine at the Mayo Clinic. Obese male subjects had significantly higher scores on the F and MA scales. Obese female subjects had significantly higher scores on the F, PD, PA, SC, and MA scales, and a significantly lower score on the Q scale than the reference population. Even though these findings show that certain personality traits as measured by the MMPI may occur more frequently in obese persons, the individual MMPI profile codes point out the presence of diverse behavior patterns among obese persons rather than a single personality pattern characteristic of obesity. There were no apparent differences in the success in achieving a loss of 10% or more of initial weight among the male and female obese subjects having normal or abnormal MMPI profiles. Obese subjects having onset of obesity before age 12 years were slightly more successful in weight reduction than those whose obesity began later than this, but the differences were not statistically significant for either the male or female subjects.", "contents": "Personality characteristics in obesity: relation of MMPI profile and age of onset of obesity to success in weight reduction. A group of 142 obese subjects was seen in an obesity clinic over a 2-year period. Of these, 116 had assessment of personality factors by the Minnesota Multiphasic Personality Inventory (MMPI), and 71 were followed for periods of 4 to 28 months in order to determine success at weight reduction by means of a conventional dietary regimen. The MMPI profiles of the obese subjects were compared to those of a general medical population of 50,000 patients seen in the Department of Internal Medicine at the Mayo Clinic. Obese male subjects had significantly higher scores on the F and MA scales. Obese female subjects had significantly higher scores on the F, PD, PA, SC, and MA scales, and a significantly lower score on the Q scale than the reference population. Even though these findings show that certain personality traits as measured by the MMPI may occur more frequently in obese persons, the individual MMPI profile codes point out the presence of diverse behavior patterns among obese persons rather than a single personality pattern characteristic of obesity. There were no apparent differences in the success in achieving a loss of 10% or more of initial weight among the male and female obese subjects having normal or abnormal MMPI profiles. Obese subjects having onset of obesity before age 12 years were slightly more successful in weight reduction than those whose obesity began later than this, but the differences were not statistically significant for either the male or female subjects."} {"id": "PMID:1274887", "title": "Change of urinary nitrogen excretion in response to low-protein diets in adults.", "content": "Data from nitrogen balance studies in young men and elderly women were analyzed for the pattern of urinary nitrogen excretion after the subjects had changed from an adequate to an essentially protein-free diet. The single exponential equation: y = P1e-p2t+P3, provided an adequate fit of the data, suggesting that a single-pool model describes the adaptive decline in urinary nitrogen excretion under these dietary conditions. Comparisons of the estimated parameters showed that the fractional rate constant, P2, was the same for both the young men and elderly women, but that the other coefficients differed between the two groups depending upon whether they were expressed per day, per kg of body weight, per unit creatinine excreted, or per kg of body cell mass. The length of time between the change in diet and the attainment of a new equilibrium in urinary nitrogen excretion (ts, or time to stability) is defined as ts = 1/p2 loge(p1/s) where s is the standard error of the fit. The average time to stability was the same in both groups (4.5 days), and 95% of the subjects reached the new equilibrium in nitrogen output within 8 days.", "contents": "Change of urinary nitrogen excretion in response to low-protein diets in adults. Data from nitrogen balance studies in young men and elderly women were analyzed for the pattern of urinary nitrogen excretion after the subjects had changed from an adequate to an essentially protein-free diet. The single exponential equation: y = P1e-p2t+P3, provided an adequate fit of the data, suggesting that a single-pool model describes the adaptive decline in urinary nitrogen excretion under these dietary conditions. Comparisons of the estimated parameters showed that the fractional rate constant, P2, was the same for both the young men and elderly women, but that the other coefficients differed between the two groups depending upon whether they were expressed per day, per kg of body weight, per unit creatinine excreted, or per kg of body cell mass. The length of time between the change in diet and the attainment of a new equilibrium in urinary nitrogen excretion (ts, or time to stability) is defined as ts = 1/p2 loge(p1/s) where s is the standard error of the fit. The average time to stability was the same in both groups (4.5 days), and 95% of the subjects reached the new equilibrium in nitrogen output within 8 days."} {"id": "PMID:1274888", "title": "Stability of vitamin B12 in the presence of ascorbic acid.", "content": "Experiments were performed in two independent laboratories, each using their own meal preparations which were exactly similar in composition to the meals described by Herbert and Jacob (J. Am. Med. Assoc. 230:241, 1974), in order to check their report that incubating meals (portions of daily food intake by man) of \"modest\" or \"high\" vitamin B12 content with increasing levels of added L-ascorbic acid (vitamin C) produced increasing destruction of vitamin B12. The present studies were performed with standardized and official methods. Vitamin B12 was determined microbiologically and by radioassay method. The results showed that 1) the vitamin B12 contents of these meals were in general agreement with values calculated from the literature for the foods involved, 2) the values obtained were manyfold higher than those reported by Herbert and Jacob, and 3) there was no deleterious effect of added ascorbic acid on the vitamin B12 content of meals, contrary to their published results.", "contents": "Stability of vitamin B12 in the presence of ascorbic acid. Experiments were performed in two independent laboratories, each using their own meal preparations which were exactly similar in composition to the meals described by Herbert and Jacob (J. Am. Med. Assoc. 230:241, 1974), in order to check their report that incubating meals (portions of daily food intake by man) of \"modest\" or \"high\" vitamin B12 content with increasing levels of added L-ascorbic acid (vitamin C) produced increasing destruction of vitamin B12. The present studies were performed with standardized and official methods. Vitamin B12 was determined microbiologically and by radioassay method. The results showed that 1) the vitamin B12 contents of these meals were in general agreement with values calculated from the literature for the foods involved, 2) the values obtained were manyfold higher than those reported by Herbert and Jacob, and 3) there was no deleterious effect of added ascorbic acid on the vitamin B12 content of meals, contrary to their published results."} {"id": "PMID:1274889", "title": "Biochemical assessment of the nutritional status of low-income pregnant women of Mexican descent.", "content": "Biochemical parameters of nutritional status were investigated in 300 women of Mexican descent during the first and second trimesters of pregnancy. Blood samples were obtained from the women during clinic visits, and measurements were made of serum iron, hemoglobin, hematocrit, serum protein, and transferrin saturation. Additionally, the nutritional status of seven vitamins was determined either by direct assay of the vitamin levels in blood or by measurement of erythrocyte enzyme stimulation. Thiamin and riboflavin were also determined in causal urine samples. Very few women, 8% or less, were classified as being low or deficient in hemoglobin, serum protein, iron, transferrin saturation, vitamin C, carotene, vitamin A, or vitamin B12. Thirty-one percent had low or deficient hematocrit values according to the guidelines used. Folic acid was the most prevalent vitamin deficiency, with 69% of the women having low or deficient serum levels. Based on the erythrocyte enzyme stimulation tests, 22% of the women were low or deficient in thiamin, 29% were low or deficient in riboflavin, and 9% were deficient in pyridoxine. None of the women had a low urinary excretion of thiamin, but 8% had excretion values of riboflavin below the acceptable level. Fewer deficiencies of thiamin and serum folic acid were observed in women taking vitamin and mineral supplements than in those who were not.", "contents": "Biochemical assessment of the nutritional status of low-income pregnant women of Mexican descent. Biochemical parameters of nutritional status were investigated in 300 women of Mexican descent during the first and second trimesters of pregnancy. Blood samples were obtained from the women during clinic visits, and measurements were made of serum iron, hemoglobin, hematocrit, serum protein, and transferrin saturation. Additionally, the nutritional status of seven vitamins was determined either by direct assay of the vitamin levels in blood or by measurement of erythrocyte enzyme stimulation. Thiamin and riboflavin were also determined in causal urine samples. Very few women, 8% or less, were classified as being low or deficient in hemoglobin, serum protein, iron, transferrin saturation, vitamin C, carotene, vitamin A, or vitamin B12. Thirty-one percent had low or deficient hematocrit values according to the guidelines used. Folic acid was the most prevalent vitamin deficiency, with 69% of the women having low or deficient serum levels. Based on the erythrocyte enzyme stimulation tests, 22% of the women were low or deficient in thiamin, 29% were low or deficient in riboflavin, and 9% were deficient in pyridoxine. None of the women had a low urinary excretion of thiamin, but 8% had excretion values of riboflavin below the acceptable level. Fewer deficiencies of thiamin and serum folic acid were observed in women taking vitamin and mineral supplements than in those who were not."} {"id": "PMID:1274890", "title": "Effect of nutrition education on the nutritional status of low-income pregnant women of Mexican descent.", "content": "Low-income pregnant women of Mexican descent were studied to determine whether their food habits could be improved by nutrition education. Biochemical indices of nutritional status were also investigated. Twenty-four-hour dietary recalls were obtained at an initial interview and again at a final interview after a nutrition education program, which was offered to a randomly selected treatment group. At the initial interview, the mean nutrient intakes that were most often below two-thirds of the Recommended Dietary Allowance (RDA) were iron, vitamin A, thiamin, and calcium. The mean energy value of the diets was also frequently below the RDA. At the final intakes, although the mean energy values and the calcium and carbohydrate of both the control and treatment groups increased significantly, the following improvements in dietary intakes were seen only within the treatment group: 1) there were significant increases in the mean intake of protein, ascorbic acid, niacin, riboflavin, and thiamin, 2) there were significant decreases in the percentage of intakes below two-thirds of the RDA for ascorbic acid and riboflavin, and 3) there was a significant decrease in the incidence of multiple low nutrient intakes. These dietary improvements, which occurred only in the treatment group, suggest the effectiveness of the nutrition education program. The most common biochemical deficiencies were of folic acid, thiamin, and riboflavin. Except for an improvement in mean serum folate levels, the biochemical indices for the treatment group did not appear to be influenced by the nutrition education. It is possible that the vitamin and mineral supplements which were taken by 80% of the women could have obscured improvements in biochemical indices which may have been due to the education program.", "contents": "Effect of nutrition education on the nutritional status of low-income pregnant women of Mexican descent. Low-income pregnant women of Mexican descent were studied to determine whether their food habits could be improved by nutrition education. Biochemical indices of nutritional status were also investigated. Twenty-four-hour dietary recalls were obtained at an initial interview and again at a final interview after a nutrition education program, which was offered to a randomly selected treatment group. At the initial interview, the mean nutrient intakes that were most often below two-thirds of the Recommended Dietary Allowance (RDA) were iron, vitamin A, thiamin, and calcium. The mean energy value of the diets was also frequently below the RDA. At the final intakes, although the mean energy values and the calcium and carbohydrate of both the control and treatment groups increased significantly, the following improvements in dietary intakes were seen only within the treatment group: 1) there were significant increases in the mean intake of protein, ascorbic acid, niacin, riboflavin, and thiamin, 2) there were significant decreases in the percentage of intakes below two-thirds of the RDA for ascorbic acid and riboflavin, and 3) there was a significant decrease in the incidence of multiple low nutrient intakes. These dietary improvements, which occurred only in the treatment group, suggest the effectiveness of the nutrition education program. The most common biochemical deficiencies were of folic acid, thiamin, and riboflavin. Except for an improvement in mean serum folate levels, the biochemical indices for the treatment group did not appear to be influenced by the nutrition education. It is possible that the vitamin and mineral supplements which were taken by 80% of the women could have obscured improvements in biochemical indices which may have been due to the education program."} {"id": "PMID:1274891", "title": "State planning of mental health services.", "content": "Planning is the vital process that links needs to solutions. The interorganizational field of human services constitutes a \"turbulent environment,\" a condition of rapid change, and there needs to be greater receptivity toward comprehensive planning on the part of state departments of mental health. Increased overlap with various welfare and educational service, advances in scientific knowledge, and shifts in general attitudes and social philosophy lead to demands for new and different types of service and require changes in approach and method. Generalized findings of a study of 14 state departments of mental health are presented.", "contents": "State planning of mental health services. Planning is the vital process that links needs to solutions. The interorganizational field of human services constitutes a \"turbulent environment,\" a condition of rapid change, and there needs to be greater receptivity toward comprehensive planning on the part of state departments of mental health. Increased overlap with various welfare and educational service, advances in scientific knowledge, and shifts in general attitudes and social philosophy lead to demands for new and different types of service and require changes in approach and method. Generalized findings of a study of 14 state departments of mental health are presented."} {"id": "PMID:1274892", "title": "Parents as therapeutic agents: the usefulness of filial therapy in a community mental health center.", "content": "Filial Therapy, a program training parents as play therapists for their own children, has been found an effective part of the functioning of a child unit in a community mental health center. The basic philosophy and principles of Filial Therapy are identified. The use of parents as therapists is viewed as consistent with the growth of the community mental health movement and the concept of treating the context in which the child resides. The structure and flexibility of this model are delineated to provide the reader with a basis to introduce Filial Therapy in his/her own setting.", "contents": "Parents as therapeutic agents: the usefulness of filial therapy in a community mental health center. Filial Therapy, a program training parents as play therapists for their own children, has been found an effective part of the functioning of a child unit in a community mental health center. The basic philosophy and principles of Filial Therapy are identified. The use of parents as therapists is viewed as consistent with the growth of the community mental health movement and the concept of treating the context in which the child resides. The structure and flexibility of this model are delineated to provide the reader with a basis to introduce Filial Therapy in his/her own setting."} {"id": "PMID:1274893", "title": "Comparison of two outcome groups in a school-based mental health project.", "content": "Two samples of school-maladjusted children responding most and least favorably to a helping program with nonprofessional child-aides were compared on demographic, referral, and program experience variables. Outcome measures other than teacher ratings used to select the samples validated the inferred improvement differences. Subjects with poor outcomes were significantly more likely to reside in the city, older, from lower socioeconomic backgrounds, and initially more maladjusted than those with good outcomes, but there were no group differences in age, repeat in grade, or program experience variables. Implications of these data for future program directions and modifications of aide-training procedures are discussed.", "contents": "Comparison of two outcome groups in a school-based mental health project. Two samples of school-maladjusted children responding most and least favorably to a helping program with nonprofessional child-aides were compared on demographic, referral, and program experience variables. Outcome measures other than teacher ratings used to select the samples validated the inferred improvement differences. Subjects with poor outcomes were significantly more likely to reside in the city, older, from lower socioeconomic backgrounds, and initially more maladjusted than those with good outcomes, but there were no group differences in age, repeat in grade, or program experience variables. Implications of these data for future program directions and modifications of aide-training procedures are discussed."} {"id": "PMID:1274896", "title": "Atrioventricular conduction in children with acute rheumatic fever.", "content": "Atrioventricular conduction was quantitatively evaluated in 118 children with acute rheumatic fever. The mean PR index in children with acute rheumatic fever, 1.06 +/- 0.38, was significantly higher than normal children or children who had febrile illness of nonrheumatic or nonstreptococcal origin (P is less than .001). Among 35 children with rheumatic fever and an abnormal PR index, the disease presented as carditis in 21, arthritis in ten, and chorea in four. The mean PR index and the frequency distribution of abnormal PR indices were significantly higher in children with carditis (P is less than .001). Five children who initially had an abnormal PR index and arthritis or chorea subsequently developed carditis. These observations suggest that children with acute rheumatic fever and abnormal PR index warrant close observation for possible clinical evidence of myocardial involvement during subsequent course of the illness.", "contents": "Atrioventricular conduction in children with acute rheumatic fever. Atrioventricular conduction was quantitatively evaluated in 118 children with acute rheumatic fever. The mean PR index in children with acute rheumatic fever, 1.06 +/- 0.38, was significantly higher than normal children or children who had febrile illness of nonrheumatic or nonstreptococcal origin (P is less than .001). Among 35 children with rheumatic fever and an abnormal PR index, the disease presented as carditis in 21, arthritis in ten, and chorea in four. The mean PR index and the frequency distribution of abnormal PR indices were significantly higher in children with carditis (P is less than .001). Five children who initially had an abnormal PR index and arthritis or chorea subsequently developed carditis. These observations suggest that children with acute rheumatic fever and abnormal PR index warrant close observation for possible clinical evidence of myocardial involvement during subsequent course of the illness."} {"id": "PMID:1274897", "title": "Estimation of gestational age in the neonate: a comparison of clinical methods.", "content": "A combined evaluation of almost all the proposed morphologic and neurologic criteria for estimating gestational age in the neonate was performed on 710 newborns of 28 to 44 weeks' gestation. It is concluded that (1) the neurologic criteria used by Dubowitz et al in combination with the external (morphologic) criteria of Farr et al give very accurate results of estimation of the gestational age; (2) equally accurate results can be obtained if those criteria with the lowest correlation coefficients--namely, are and leg recoil, degree of edema, and appearance of the genitalia--are omitted; and (3) the use of only nine external criteria, the assessment of which is easier to perform on sick babies, gives an estimation of gestational age that is accurate for clinical purposes (r=0.878).", "contents": "Estimation of gestational age in the neonate: a comparison of clinical methods. A combined evaluation of almost all the proposed morphologic and neurologic criteria for estimating gestational age in the neonate was performed on 710 newborns of 28 to 44 weeks' gestation. It is concluded that (1) the neurologic criteria used by Dubowitz et al in combination with the external (morphologic) criteria of Farr et al give very accurate results of estimation of the gestational age; (2) equally accurate results can be obtained if those criteria with the lowest correlation coefficients--namely, are and leg recoil, degree of edema, and appearance of the genitalia--are omitted; and (3) the use of only nine external criteria, the assessment of which is easier to perform on sick babies, gives an estimation of gestational age that is accurate for clinical purposes (r=0.878)."} {"id": "PMID:1274898", "title": "Children with superior intelligence at 7 years of age: a prospective study of the influence of perinatal, medical, and socioeconomic factors.", "content": "Perinatal and medical information, growth, and the social background of 258 children who, in a prospective study, had superior intelligence at 7 years of age were reviewed. The subjects were divided into three categories on the basis of the results of psychological evaluation at age 7. Comparisons were made between those with superior (intelligence quotient greater than or equal to 120), average (IQ between 80 and 119), and low intelligence (IQ less than or equal to 79). A favorable parental social and educational background was the best correlate of superior intelligence in the children. Larger head size from 1 year of age was an early finding associated with superior intelligence. Greater height and weight, from 4 years of age were later findings. Correlations between psychological performance at ages 4 and 7 years were statistically significant. Perinatal factors and medical complications did not affect the intellectual status of children with superior intelligence.", "contents": "Children with superior intelligence at 7 years of age: a prospective study of the influence of perinatal, medical, and socioeconomic factors. Perinatal and medical information, growth, and the social background of 258 children who, in a prospective study, had superior intelligence at 7 years of age were reviewed. The subjects were divided into three categories on the basis of the results of psychological evaluation at age 7. Comparisons were made between those with superior (intelligence quotient greater than or equal to 120), average (IQ between 80 and 119), and low intelligence (IQ less than or equal to 79). A favorable parental social and educational background was the best correlate of superior intelligence in the children. Larger head size from 1 year of age was an early finding associated with superior intelligence. Greater height and weight, from 4 years of age were later findings. Correlations between psychological performance at ages 4 and 7 years were statistically significant. Perinatal factors and medical complications did not affect the intellectual status of children with superior intelligence."} {"id": "PMID:1274899", "title": "Nonaccidental trauma and failure to thrive.", "content": "Charts were reviewed of 140 children who were discharged from Denver General Hospital (DGH) with diagnoses of nonaccidental trauma or failure to thrive. These children were all enrolled in a neighborhood health program. It was found that boys and girls were affected equally and that most of these children were under 3 years of age. In relation to their representation in the Neighborhood Health Program, more white children were abused or failed to thrive than children from other racial groups. A disproportionate number of children had birth weights under 2,500 gm as compared to children born at DGH. Young parents who were raised in disrupted families were involved in child abuse more frequently than were individuals from more stable families. Bruising was the most frequent injury and was most prevalent among boys under 3 years of age. Fractures were the second most common injury and occurred equally among boys and girls. There appeared to be a seasonal variation in the incidence of abuse.", "contents": "Nonaccidental trauma and failure to thrive. Charts were reviewed of 140 children who were discharged from Denver General Hospital (DGH) with diagnoses of nonaccidental trauma or failure to thrive. These children were all enrolled in a neighborhood health program. It was found that boys and girls were affected equally and that most of these children were under 3 years of age. In relation to their representation in the Neighborhood Health Program, more white children were abused or failed to thrive than children from other racial groups. A disproportionate number of children had birth weights under 2,500 gm as compared to children born at DGH. Young parents who were raised in disrupted families were involved in child abuse more frequently than were individuals from more stable families. Bruising was the most frequent injury and was most prevalent among boys under 3 years of age. Fractures were the second most common injury and occurred equally among boys and girls. There appeared to be a seasonal variation in the incidence of abuse."} {"id": "PMID:1274900", "title": "Blood pressure, salt preference, salt threshold, and relative weight.", "content": "This study was performed to observe the relationships of salt preference, salt threshold, the relative weight to blood pressure. Three groups were selected from 4,800 school children on the basis of mean blood pressure: less than or equal to fifth percentile, in the area of the 50th percentile, and greater than or equal to 95th percentile. Salt threshold was determined by titrating, on each subject's tongue, solutions ranging from 1 to 60 millimols/liter of sodium chloride. Salt preference was tested by the addition of salt by each subject to unsalted tomato juice and beef broth according to individual taste. The samples were then analyzed for sodium concentration. The coefficient of correlation for the amount of salt added to juice and broth was significant (r=0.63). There was no relationship of salt threshold to preference, nor did threshold or preference relate to blood pressure. Relative weight was related to blood pressure range being the most obese.", "contents": "Blood pressure, salt preference, salt threshold, and relative weight. This study was performed to observe the relationships of salt preference, salt threshold, the relative weight to blood pressure. Three groups were selected from 4,800 school children on the basis of mean blood pressure: less than or equal to fifth percentile, in the area of the 50th percentile, and greater than or equal to 95th percentile. Salt threshold was determined by titrating, on each subject's tongue, solutions ranging from 1 to 60 millimols/liter of sodium chloride. Salt preference was tested by the addition of salt by each subject to unsalted tomato juice and beef broth according to individual taste. The samples were then analyzed for sodium concentration. The coefficient of correlation for the amount of salt added to juice and broth was significant (r=0.63). There was no relationship of salt threshold to preference, nor did threshold or preference relate to blood pressure. Relative weight was related to blood pressure range being the most obese."} {"id": "PMID:1274903", "title": "Arteriovenous malformation of the vein of Galen: treatment in a neonate.", "content": "Heart failure in a 2-day-old infant was not readily explained by clinical examination. Cardiac catheterization suggested an intracranial arteriovenous (AV) fistula, and cerebral arteriography showed a malformation of the vein of Galen. The major feeding arteries were surgically obliterated. At age 27 months, the boy has normal mentation but moderate left hemiparesis. Review of the literature disclosed 39 other infants with AV malformations of the vein of Galen producing heart failure before age 3 months. Most of them were boys, and had cyanosis, a systolic murmer, cranial bruit, cardiomegaly, and right bentricular hypertrophy. Only three of the 13 who had surgery for their malformation survived. Removal of the malformation is difficult; obliteration of the nutrient vessels, using the operating microscope, is the currently accepted treatment.", "contents": "Arteriovenous malformation of the vein of Galen: treatment in a neonate. Heart failure in a 2-day-old infant was not readily explained by clinical examination. Cardiac catheterization suggested an intracranial arteriovenous (AV) fistula, and cerebral arteriography showed a malformation of the vein of Galen. The major feeding arteries were surgically obliterated. At age 27 months, the boy has normal mentation but moderate left hemiparesis. Review of the literature disclosed 39 other infants with AV malformations of the vein of Galen producing heart failure before age 3 months. Most of them were boys, and had cyanosis, a systolic murmer, cranial bruit, cardiomegaly, and right bentricular hypertrophy. Only three of the 13 who had surgery for their malformation survived. Removal of the malformation is difficult; obliteration of the nutrient vessels, using the operating microscope, is the currently accepted treatment."} {"id": "PMID:1274904", "title": "Appendicovesical fistula in childhood: a rare complication of ruptured appendix.", "content": "The diagnosis of appendicovesical fistula is difficult and usually delayed. This is most unfortunate, since surgery is uniformly successful. The case we report reemphasizes the diagnostic value of the rectal examination, intravenous pyelogram, and foiding cystogram in a child with subacute or chronic abdominal pain. Only an awareness of this condition on the part of the attending physician will lead to prompt diagnosis and definitive therapy.", "contents": "Appendicovesical fistula in childhood: a rare complication of ruptured appendix. The diagnosis of appendicovesical fistula is difficult and usually delayed. This is most unfortunate, since surgery is uniformly successful. The case we report reemphasizes the diagnostic value of the rectal examination, intravenous pyelogram, and foiding cystogram in a child with subacute or chronic abdominal pain. Only an awareness of this condition on the part of the attending physician will lead to prompt diagnosis and definitive therapy."} {"id": "PMID:1274905", "title": "Wolman disease in a Pakistani infant.", "content": "In an infant with Wolman disease, confirmation of the diagnosis was made before death or radioological and enzymological criteria. It is the first case reported in a Pakistani infant.", "contents": "Wolman disease in a Pakistani infant. In an infant with Wolman disease, confirmation of the diagnosis was made before death or radioological and enzymological criteria. It is the first case reported in a Pakistani infant."} {"id": "PMID:1274911", "title": "Multidisciplinary Conferences in Gastroenterology. Cardiovascular effects of severe liver disease.", "content": "This is the definitive review of the cardiovascular effects of liver disease. Physiologic and pathologic studies accomplished primarily in the 1950s and 1960s have been applied to a case of a 16-year-old boy with cirrhosis of the liver who presented with weakness, dyspnea, cyanosis, and clubbing. The probable mechanisms for his signs and symptoms are discussed in detail. The cause for the hyperkinetic circulation is unknown. By exclusion, the cyanosis is attributed to intrapulmonary shunting. Portapulmonary shunts are not quantitatively important. The suitability of the terms micronodular and macronodular cirrhosis is highlighted. Indications for various types of surgical portal shunts are discussed. The value of preoperative hemodynamic measurements of the portal circulation to the individual patient is debated. A liver transplant is considered in this case with no promising medical therapy and a very poor prognosis. The renal disease manifested by red cell casts in the urine is thought to be caused by an immunologic reaction in the kidney somehow related to his liver disease. This discussion is led by Dr. Jack Myers, but his opinions are correlated with those of a pathologist, radiologist, surgeon, and gastroenterologist. It is a clinical tour de force, although not all the predictions are confirmed by laboratory studies such as this patient's hepatic wedge pressure, pulmonary artery pressure, and cardiac fluoroscopy.", "contents": "Multidisciplinary Conferences in Gastroenterology. Cardiovascular effects of severe liver disease. This is the definitive review of the cardiovascular effects of liver disease. Physiologic and pathologic studies accomplished primarily in the 1950s and 1960s have been applied to a case of a 16-year-old boy with cirrhosis of the liver who presented with weakness, dyspnea, cyanosis, and clubbing. The probable mechanisms for his signs and symptoms are discussed in detail. The cause for the hyperkinetic circulation is unknown. By exclusion, the cyanosis is attributed to intrapulmonary shunting. Portapulmonary shunts are not quantitatively important. The suitability of the terms micronodular and macronodular cirrhosis is highlighted. Indications for various types of surgical portal shunts are discussed. The value of preoperative hemodynamic measurements of the portal circulation to the individual patient is debated. A liver transplant is considered in this case with no promising medical therapy and a very poor prognosis. The renal disease manifested by red cell casts in the urine is thought to be caused by an immunologic reaction in the kidney somehow related to his liver disease. This discussion is led by Dr. Jack Myers, but his opinions are correlated with those of a pathologist, radiologist, surgeon, and gastroenterologist. It is a clinical tour de force, although not all the predictions are confirmed by laboratory studies such as this patient's hepatic wedge pressure, pulmonary artery pressure, and cardiac fluoroscopy."} {"id": "PMID:1274916", "title": "Crohn's disease of the colon. Analysis of the diagnostic value of radiology, endoscopy, and histology.", "content": "Radiologic, endoscopic, and histologic features were analyzed in 15 patients with Crohn's disease of the colon. Radiologic findings were considered of diagnostic value in only 6 (40%), characteristic endoscopic lesions were found in 13 (87%) and diagnostic histologic features in 11 (73%). Endoscopy combined with biopsy was diagnostic in all 15 cases. The extent of involvement of endoscopy frequently disagreed with the radiologic assessment, particularly in the rectosigmoid area. Studies in 8 patients indicate that sigmoidoscopy and coloscopy with multiple biopsies provide an accurate alternative to radiology to estimate the extent and severity of the lesions and their evolution during corticosteroid and/or azathioprine treatment.", "contents": "Crohn's disease of the colon. Analysis of the diagnostic value of radiology, endoscopy, and histology. Radiologic, endoscopic, and histologic features were analyzed in 15 patients with Crohn's disease of the colon. Radiologic findings were considered of diagnostic value in only 6 (40%), characteristic endoscopic lesions were found in 13 (87%) and diagnostic histologic features in 11 (73%). Endoscopy combined with biopsy was diagnostic in all 15 cases. The extent of involvement of endoscopy frequently disagreed with the radiologic assessment, particularly in the rectosigmoid area. Studies in 8 patients indicate that sigmoidoscopy and coloscopy with multiple biopsies provide an accurate alternative to radiology to estimate the extent and severity of the lesions and their evolution during corticosteroid and/or azathioprine treatment."} {"id": "PMID:1274917", "title": "Bile-induced acute erosive gastritis. Its prevention by antacid, cholestyramine, and prostaglandin E2.", "content": "Intragastric administration of whole bile-produced acute erosive gastritis in rats. Concomitant intragastric administration of prostaglandin E2, Cholestyramine and an antacid (Maalox) was effective in preventing this type of acute erosive gastritis. The protective rffect of prostaglandin E - 2 in this regard was significantly more marked as compared to Cholestyramine and Maalox.", "contents": "Bile-induced acute erosive gastritis. Its prevention by antacid, cholestyramine, and prostaglandin E2. Intragastric administration of whole bile-produced acute erosive gastritis in rats. Concomitant intragastric administration of prostaglandin E2, Cholestyramine and an antacid (Maalox) was effective in preventing this type of acute erosive gastritis. The protective rffect of prostaglandin E - 2 in this regard was significantly more marked as compared to Cholestyramine and Maalox."} {"id": "PMID:1274918", "title": "Pericarditis associated with ulcerative colitis and Crohn's disease.", "content": "Extracolonic manifestations of inflammatory bowel disease are common and diverse. However, cardiac complications are unusual and we therefore wish to report two cases in which pericarditis occurred. The first was a patient with Crohn's disease of the colon, in whom the pericarditis developed postoperatively. In the second case an acute pericarditis came on simultaneously with the initial presentation of ulcerative colitis.", "contents": "Pericarditis associated with ulcerative colitis and Crohn's disease. Extracolonic manifestations of inflammatory bowel disease are common and diverse. However, cardiac complications are unusual and we therefore wish to report two cases in which pericarditis occurred. The first was a patient with Crohn's disease of the colon, in whom the pericarditis developed postoperatively. In the second case an acute pericarditis came on simultaneously with the initial presentation of ulcerative colitis."} {"id": "PMID:1274919", "title": "Serum bile acids in alcoholic liver disease. Comparison with histological features of the disease.", "content": "Fasting serum bile acids were measured by gas-liquid chromatography in 64 patients with alcoholic liver disease and compared with histological features in their percutaneous liver biopsy specimens. Total bile acid concentrations were normal (less than 2 mug/ml) or minimally increased in 6 patients in whom fatty infiltration was the only hepatic lesion. In the remaining 58 patients with more severe histological lesions, levels were increased in 93%, whereas serum bilirubins were elevated in only 43%. Chenodeoxycholic acid was usually the predominant serum bile acid, regardless of the degree of necrosis or connective tissue change in the biopsy specimen. Only small amounts of the secondary bile acids, deoxycholic acid and lithocholic acid, were detected. Levels of these secondary bile acids did not correlate with histological features.", "contents": "Serum bile acids in alcoholic liver disease. Comparison with histological features of the disease. Fasting serum bile acids were measured by gas-liquid chromatography in 64 patients with alcoholic liver disease and compared with histological features in their percutaneous liver biopsy specimens. Total bile acid concentrations were normal (less than 2 mug/ml) or minimally increased in 6 patients in whom fatty infiltration was the only hepatic lesion. In the remaining 58 patients with more severe histological lesions, levels were increased in 93%, whereas serum bilirubins were elevated in only 43%. Chenodeoxycholic acid was usually the predominant serum bile acid, regardless of the degree of necrosis or connective tissue change in the biopsy specimen. Only small amounts of the secondary bile acids, deoxycholic acid and lithocholic acid, were detected. Levels of these secondary bile acids did not correlate with histological features."} {"id": "PMID:1274920", "title": "Acute hemorrhagic pancreatitis in the dog. IV. Treatment with vasopressin.", "content": "Acute hemorrhagic pancreatitis was experimentally induced in the dog by the closed-duodenal-loop technique. The disease process was modified and partially reversed by intravenous infusions of vasopressin, as indicated by some of our tests for pancreatitis as well as histologic examination of the pancreas.", "contents": "Acute hemorrhagic pancreatitis in the dog. IV. Treatment with vasopressin. Acute hemorrhagic pancreatitis was experimentally induced in the dog by the closed-duodenal-loop technique. The disease process was modified and partially reversed by intravenous infusions of vasopressin, as indicated by some of our tests for pancreatitis as well as histologic examination of the pancreas."} {"id": "PMID:1274921", "title": "Effect of synthetic 15-methyl analog of PGE2 on gastric acid and serum gastrin response to peptone meal, pentagastrin, and histamine in duodenal ulcer patients.", "content": "The effect of 15(S)-15-methyl PGE2, methyl ester (15-ME-PGE2), used intravenously in a standard dose of 0.5 mug/kg-hr on gastric secretion and serum gastrin level was studied in 6 duodenal ulcer patients. 15-Me-PGE2 caused an immediate and almost complete inhibition of basal gastric acid and pepsin secretion. Acid secretion induced by a peptone meal and determined by intragastric titration technique was almost as high as the maximal response to histamine and accompanied by a significant rise in serum concentration of immunoassayable gastrin. 15-Me-PGE2 caused a sudden and complete inhibition of gastric acid response to a peptone meal. 15-Me-PGE2 did not significantly affect serum gastrin levels both under basal conditions and in response to a peptone meal. Gastric acid and pepsin output induced by maximal stimulation with pentagastrin (4 mug/kg-hr) was inhibited by 15-Me-PGE2 by about 70% and that induced by histamine by about 45%. After the withdrawal of 15-Me-PGE2 infusion, gastric secretion remained reduced for the remainder of the test. We conclude that 15-Me-PGE2 is a very strong inhibitor of gastric acid and pepsin secretion induced by various secretory stimuli, particularly under basal conditions and in response to a meal. In view of prolonged inhibitory activity, 15-Me-PGE2 may have clinical potential in the treatment of peptic ulcer disease.", "contents": "Effect of synthetic 15-methyl analog of PGE2 on gastric acid and serum gastrin response to peptone meal, pentagastrin, and histamine in duodenal ulcer patients. The effect of 15(S)-15-methyl PGE2, methyl ester (15-ME-PGE2), used intravenously in a standard dose of 0.5 mug/kg-hr on gastric secretion and serum gastrin level was studied in 6 duodenal ulcer patients. 15-Me-PGE2 caused an immediate and almost complete inhibition of basal gastric acid and pepsin secretion. Acid secretion induced by a peptone meal and determined by intragastric titration technique was almost as high as the maximal response to histamine and accompanied by a significant rise in serum concentration of immunoassayable gastrin. 15-Me-PGE2 caused a sudden and complete inhibition of gastric acid response to a peptone meal. 15-Me-PGE2 did not significantly affect serum gastrin levels both under basal conditions and in response to a peptone meal. Gastric acid and pepsin output induced by maximal stimulation with pentagastrin (4 mug/kg-hr) was inhibited by 15-Me-PGE2 by about 70% and that induced by histamine by about 45%. After the withdrawal of 15-Me-PGE2 infusion, gastric secretion remained reduced for the remainder of the test. We conclude that 15-Me-PGE2 is a very strong inhibitor of gastric acid and pepsin secretion induced by various secretory stimuli, particularly under basal conditions and in response to a meal. In view of prolonged inhibitory activity, 15-Me-PGE2 may have clinical potential in the treatment of peptic ulcer disease."} {"id": "PMID:1274922", "title": "Kinetics of the subcellular distribution of iron and cobalt in the intestinal mucosa of the rat.", "content": "A differential centrifugation technique was used to compare the subcellular distribution of labeled iron (Fe) and cobalt (Co) in iron-deficient animals (FeD), in which transport was active, with iron-loaded animals (FeL), in which transport was by diffusion. In FeL the amount of Fe and Co in each subcellular fraction was dependent upon dose; there was a linear relation between the amount of Fe or Co in each fraction and metal absorption. In FeD a curvilinear relation was noted between both Fe dose and absorption, and the amount of Fe in the particulate fractions I and II. In contrast, a linear relation was noted between both dose and absorption, and the smaller amounts of Fe in the other fractions. Most of the Co was in V (\"soluble\"), and the relation between Co in all the fractions and absorption was linear. The addition of Co to the Fe test dose was associated with a decrease in Fe in I and II. The results suggest that a constituent(s) in the particulate fractions I and II is involved in the enhanced absorption of Fe in FeD. The subcellular fraction responsible for the increased Co absorption in FeD was not identified.", "contents": "Kinetics of the subcellular distribution of iron and cobalt in the intestinal mucosa of the rat. A differential centrifugation technique was used to compare the subcellular distribution of labeled iron (Fe) and cobalt (Co) in iron-deficient animals (FeD), in which transport was active, with iron-loaded animals (FeL), in which transport was by diffusion. In FeL the amount of Fe and Co in each subcellular fraction was dependent upon dose; there was a linear relation between the amount of Fe or Co in each fraction and metal absorption. In FeD a curvilinear relation was noted between both Fe dose and absorption, and the amount of Fe in the particulate fractions I and II. In contrast, a linear relation was noted between both dose and absorption, and the smaller amounts of Fe in the other fractions. Most of the Co was in V (\"soluble\"), and the relation between Co in all the fractions and absorption was linear. The addition of Co to the Fe test dose was associated with a decrease in Fe in I and II. The results suggest that a constituent(s) in the particulate fractions I and II is involved in the enhanced absorption of Fe in FeD. The subcellular fraction responsible for the increased Co absorption in FeD was not identified."} {"id": "PMID:1274923", "title": "Diagnosis of Barrett's esophagus by pertechnetate radionuclide.", "content": "In Barrett's esophagus the normal stratified squamous epithelium of esophagus is replaced by columnar epithelium and other charcteristics of gastric mucosa. Barrett's esophagus has an increased tendency to bleed and is more prone to undergo malignant change. There are many procedures used to diagnose this entity, but only by serial and multiple esophageal mucosal biopsies can the diagnosis be confirmed. Harper et al (2) demonstrated an early and intense uptake of 99m Tc pertechnetate by the stomach in animals. Since the Barrett's esophagus is lined by gastric mucosa, pertechnetate scintigraphy was used as a screening procedure. The criteria for a postive scan was an area of increased uptake of technetium extending above the normal dense uptake of stomach configuration. Pertechnetate scintigraphy was performed in 4 patients with Barrett's esophagus and 6 controls with only one false negative result. Thus pertechnetate scintigraphy is a rapid, safe, and atraumatic screening procedure.", "contents": "Diagnosis of Barrett's esophagus by pertechnetate radionuclide. In Barrett's esophagus the normal stratified squamous epithelium of esophagus is replaced by columnar epithelium and other charcteristics of gastric mucosa. Barrett's esophagus has an increased tendency to bleed and is more prone to undergo malignant change. There are many procedures used to diagnose this entity, but only by serial and multiple esophageal mucosal biopsies can the diagnosis be confirmed. Harper et al (2) demonstrated an early and intense uptake of 99m Tc pertechnetate by the stomach in animals. Since the Barrett's esophagus is lined by gastric mucosa, pertechnetate scintigraphy was used as a screening procedure. The criteria for a postive scan was an area of increased uptake of technetium extending above the normal dense uptake of stomach configuration. Pertechnetate scintigraphy was performed in 4 patients with Barrett's esophagus and 6 controls with only one false negative result. Thus pertechnetate scintigraphy is a rapid, safe, and atraumatic screening procedure."} {"id": "PMID:1274924", "title": "Pancreatic ascites: successful treatment with pancreatic radiation.", "content": "A 51-year-old man with clinical and laboratory findings consistent with the diagnosis of pancreatic ascites is reported. Response to usual medical measures was inadequate. Single-dose irradiation to the pancreatic area (550 rads) resulted in marked improvement in his ascites. Operative pancreatogram months later revealed no evidence of ductal leakage. Low-dose pancreatic irradiation may be a unseful therapeutic adjunct in the older, high-risk patient with pancreatic ascites in whom surgery is not considered feasible.", "contents": "Pancreatic ascites: successful treatment with pancreatic radiation. A 51-year-old man with clinical and laboratory findings consistent with the diagnosis of pancreatic ascites is reported. Response to usual medical measures was inadequate. Single-dose irradiation to the pancreatic area (550 rads) resulted in marked improvement in his ascites. Operative pancreatogram months later revealed no evidence of ductal leakage. Low-dose pancreatic irradiation may be a unseful therapeutic adjunct in the older, high-risk patient with pancreatic ascites in whom surgery is not considered feasible."} {"id": "PMID:1274925", "title": "Nonpancreatic-type hyperamylasemia associated with pancreatic cancer.", "content": "Isoamylase analysis of the serum and urine of a patient with anaplastic spindel cell carcinoma of the pancreas revealed that virtually all of the serum amylase and almost all of the urine amylase behaved chromatographically as the salivary (S) type. Both the serum and urine amylases were bound by a substance derived from a macroamylase complex which had been shown to bind only salivary amylase and to lack any affinity for pancreatitis (P) type amylase. The ratio of amylase to creatinine clearance was markedly increased (12.5%) without evidence of acute pancreatitis at autopsy and despite the presence of only a minute amount of P-type isoamylase in the serum.", "contents": "Nonpancreatic-type hyperamylasemia associated with pancreatic cancer. Isoamylase analysis of the serum and urine of a patient with anaplastic spindel cell carcinoma of the pancreas revealed that virtually all of the serum amylase and almost all of the urine amylase behaved chromatographically as the salivary (S) type. Both the serum and urine amylases were bound by a substance derived from a macroamylase complex which had been shown to bind only salivary amylase and to lack any affinity for pancreatitis (P) type amylase. The ratio of amylase to creatinine clearance was markedly increased (12.5%) without evidence of acute pancreatitis at autopsy and despite the presence of only a minute amount of P-type isoamylase in the serum."} {"id": "PMID:1274927", "title": "Parameters of liver spleen scans as an indication of portal hypertension.", "content": "In 37 patients with suspected portal hypertension, the bone marrow and splenic uptake on 99mTc-sulfur colloid liver spleen scans correlated with increased portal pressures. The degree of increase was not possible to predict from the scans. In portacaval shunt patients, those with normal portal pressures could not be separated from those with elevated pressures on the basis of the scan alone.", "contents": "Parameters of liver spleen scans as an indication of portal hypertension. In 37 patients with suspected portal hypertension, the bone marrow and splenic uptake on 99mTc-sulfur colloid liver spleen scans correlated with increased portal pressures. The degree of increase was not possible to predict from the scans. In portacaval shunt patients, those with normal portal pressures could not be separated from those with elevated pressures on the basis of the scan alone."} {"id": "PMID:1274928", "title": "Peroral staining method with toluidine blue as an aid in the diagnosis of malignant gastric lesions.", "content": "Peroral, intragastric staining method with toluidine blue was performed in 42 patients with suspected neoplastic lesions of the stomach. Fifteen out of 18 malignant lesions and one out of 13 benign lesions were stained. Normal mucosa, areas of gastritis and most of the benign lesions appeared unchanged. According to our results, the use of toluidine blue staining method prior to endoscopy might be of help in demonstrating minute malignant lesions of gastric mucosa and in the differential diagnosis between benign and malignant ulcers of the stomach.", "contents": "Peroral staining method with toluidine blue as an aid in the diagnosis of malignant gastric lesions. Peroral, intragastric staining method with toluidine blue was performed in 42 patients with suspected neoplastic lesions of the stomach. Fifteen out of 18 malignant lesions and one out of 13 benign lesions were stained. Normal mucosa, areas of gastritis and most of the benign lesions appeared unchanged. According to our results, the use of toluidine blue staining method prior to endoscopy might be of help in demonstrating minute malignant lesions of gastric mucosa and in the differential diagnosis between benign and malignant ulcers of the stomach."} {"id": "PMID:1274929", "title": "Emotion-related gastritis.", "content": "The relationship of emotional stress to abnormalities of the gastric mucosa was considered in a review of 788 consecutive upper gastrointestinal endoscopies. Fifty-three precent of patients with gastritis not related to any generally accepted predisposing or precipitating cause had significant emotional problems documented on their clinical records, while only 10% of the comparable group of duodenal ulcer patients and 25% of a similar group of medical in-patients had significant emotional problems documented. Since this difference was statistically significant (P less than 0.01 and P less than 0.05, respectively), the data suggest that emotional stress may play a contributing role in the production of gastric mucosal abnormaltieis.", "contents": "Emotion-related gastritis. The relationship of emotional stress to abnormalities of the gastric mucosa was considered in a review of 788 consecutive upper gastrointestinal endoscopies. Fifty-three precent of patients with gastritis not related to any generally accepted predisposing or precipitating cause had significant emotional problems documented on their clinical records, while only 10% of the comparable group of duodenal ulcer patients and 25% of a similar group of medical in-patients had significant emotional problems documented. Since this difference was statistically significant (P less than 0.01 and P less than 0.05, respectively), the data suggest that emotional stress may play a contributing role in the production of gastric mucosal abnormaltieis."} {"id": "PMID:1274930", "title": "A new radioisotopic technic for the measurement of gastric emptying time of solid meal.", "content": "The suitability of a radiopharmaceutical for measuring gastric emptying time of solid meal is described. The gastric emptying T1/2 value of solid meal in normal individuals has been established. Both animal and human experiments indicate 99mTc-DTPA to be an ideal nonabsorbable marker for determing gastric emptying rate and for other gastrointestinal studies as well. Studies are now underway to determine gastric emptying time in patients with gastrectomy and gastrojejunostomy, vagotomy, pyloroplasty, etc.", "contents": "A new radioisotopic technic for the measurement of gastric emptying time of solid meal. The suitability of a radiopharmaceutical for measuring gastric emptying time of solid meal is described. The gastric emptying T1/2 value of solid meal in normal individuals has been established. Both animal and human experiments indicate 99mTc-DTPA to be an ideal nonabsorbable marker for determing gastric emptying rate and for other gastrointestinal studies as well. Studies are now underway to determine gastric emptying time in patients with gastrectomy and gastrojejunostomy, vagotomy, pyloroplasty, etc."} {"id": "PMID:1274931", "title": "Duodenal contraction wave patterns in patients with and without ulcer.", "content": "To determine whether differences in frequency of specific wave sequences and types existed in the four parts of the duodenum in ulcer subjects and controls an analysis of contraction waves in 14 controls and 10 duodenal ulcer patients of similar age was done by a statistical analysis of differences between the two groups. A water-perfused tube system was used. Differences in motor activity, namely, decreased frequency of waves in the proximal duodenum and increased frequency of waves in the distal duodenum in ulcer subjects as compared to controls was demonstrated. This involved a statistically significant decrease in numbers of mixing (or basic rhythm) waves in the proximal duodenum. Increased numbers of isolated waves were found in ulcer patients in the distal duodenum. The predominant types of contraction waves in both ulcer and control subjects were isolated and simultaneous waves, with peristaltic waves were less common in the fasting state. These findings suggest that differences exist in the types of contraction waves in duodenal ulcer subjects compared to controls.", "contents": "Duodenal contraction wave patterns in patients with and without ulcer. To determine whether differences in frequency of specific wave sequences and types existed in the four parts of the duodenum in ulcer subjects and controls an analysis of contraction waves in 14 controls and 10 duodenal ulcer patients of similar age was done by a statistical analysis of differences between the two groups. A water-perfused tube system was used. Differences in motor activity, namely, decreased frequency of waves in the proximal duodenum and increased frequency of waves in the distal duodenum in ulcer subjects as compared to controls was demonstrated. This involved a statistically significant decrease in numbers of mixing (or basic rhythm) waves in the proximal duodenum. Increased numbers of isolated waves were found in ulcer patients in the distal duodenum. The predominant types of contraction waves in both ulcer and control subjects were isolated and simultaneous waves, with peristaltic waves were less common in the fasting state. These findings suggest that differences exist in the types of contraction waves in duodenal ulcer subjects compared to controls."} {"id": "PMID:1274932", "title": "Current thoughts on the surgical treatment of rectal cancer.", "content": "From August, 1971 to May, 1974, 52 cases of rectal cancer belonging to different groups, according to Mason's classification, were seen at the First Surgical Department, University of Athens Medical School. In the majority of the cases the tumor was removed by combined abdominoperineal resection; the variety of other surgical methods in the treatment of rectal cancer are discussed. Emphasis is focused on certain important technical aspects in the surgery of rectal cancer: 1. the need for thorough preoperative preparation of the bowel; 2. the ligation of the inferior mesenteric artery at its origin from the aorta; 3. the intraluminal infusion of cytotoxic agents into the tumor-bearing segment after ligation of the inferior mesenteric vein; 4. the idea of the intra-arterial regional chemotherapy, during the operation; 5. the demarcation of the area with radiopaque clips for acute postoperative radiation,when residual tumor is left behind. The authors consider adherence to the above technical details critical in achieving good surgical results.", "contents": "Current thoughts on the surgical treatment of rectal cancer. From August, 1971 to May, 1974, 52 cases of rectal cancer belonging to different groups, according to Mason's classification, were seen at the First Surgical Department, University of Athens Medical School. In the majority of the cases the tumor was removed by combined abdominoperineal resection; the variety of other surgical methods in the treatment of rectal cancer are discussed. Emphasis is focused on certain important technical aspects in the surgery of rectal cancer: 1. the need for thorough preoperative preparation of the bowel; 2. the ligation of the inferior mesenteric artery at its origin from the aorta; 3. the intraluminal infusion of cytotoxic agents into the tumor-bearing segment after ligation of the inferior mesenteric vein; 4. the idea of the intra-arterial regional chemotherapy, during the operation; 5. the demarcation of the area with radiopaque clips for acute postoperative radiation,when residual tumor is left behind. The authors consider adherence to the above technical details critical in achieving good surgical results."} {"id": "PMID:1274933", "title": "Crohn's disease of the appendix presenting as acute appendicitis.", "content": "A patient is reported who initially presented with findings simulating acute appendicitis and who was subsequently found to have Crohn's disease isolated to the appendix. Although the hazard of appendectomy in Crohn's disease is well known, it is interesting that none of the known patients with isolated appendiceal Crohn's disease has developed a fistula. Three of the 15 reported cases of Crohn's disease solely involving the appendix developed granulomatous changes involving other regions of the bowel as long as four years following the initial diagnosis. Because of the rarity of this condition, however, specific conclusions regarding the likehood of future recurrence cannot be drawn. We stress increased physician awareness of this entity in order to emphasize long-term follow-up for such patients.", "contents": "Crohn's disease of the appendix presenting as acute appendicitis. A patient is reported who initially presented with findings simulating acute appendicitis and who was subsequently found to have Crohn's disease isolated to the appendix. Although the hazard of appendectomy in Crohn's disease is well known, it is interesting that none of the known patients with isolated appendiceal Crohn's disease has developed a fistula. Three of the 15 reported cases of Crohn's disease solely involving the appendix developed granulomatous changes involving other regions of the bowel as long as four years following the initial diagnosis. Because of the rarity of this condition, however, specific conclusions regarding the likehood of future recurrence cannot be drawn. We stress increased physician awareness of this entity in order to emphasize long-term follow-up for such patients."} {"id": "PMID:1274934", "title": "Pseudomembraneous colitis associated with antibiotics.", "content": "Radiographic manifestations of the colon on barium enema examination in two cases of antibiotic-induced pseudomembraneous colitis are presented. The radiographic findings are ulcerations, shaggy edematous mucosa and excessive mucus secretion. Although these roentgenorgraphic findings could not be differentiated from other inflammatory bowel disease, the antibiotic-induced enterocolitis must be included in the differential diagnosis whenever there is a clinical history of recent antibiotic therapy.", "contents": "Pseudomembraneous colitis associated with antibiotics. Radiographic manifestations of the colon on barium enema examination in two cases of antibiotic-induced pseudomembraneous colitis are presented. The radiographic findings are ulcerations, shaggy edematous mucosa and excessive mucus secretion. Although these roentgenorgraphic findings could not be differentiated from other inflammatory bowel disease, the antibiotic-induced enterocolitis must be included in the differential diagnosis whenever there is a clinical history of recent antibiotic therapy."} {"id": "PMID:1274936", "title": "Primary sclerosing cholangitis. A report of nine cases and clinical review.", "content": "Nine cases of primary sclerosing cholangitis were reviewed as to methods of diagnosis, association with other disease states and clinical course of the patients. There were four cases of primary sclerosing cholangitis occurring alone, four cases associated with inflammatory bowel disease (three with chronic ulcerative colitis and one case with proctosigmoiditis) and one case associated with porphyria cutanea tarda. All cases of primary sclerosing cholangitis occurring alone, progressed to secondary biliary cirrhosis, however, none of the cases associated with chronic ulcerative colitis progressed to secondary biliary cirrhosis. In all cases, the diagnosis was established by operative findings and biopsy results. The mode of clinical presentation was similar in all cases and was characterized by slowly progressive jaundice. Intravenous and oral cholangiography were not useful in establishing a diagnosis but endoscopic retrograde cholangiography offers preoperative diagnostic hope and use for follow-up evaluation. One case with ulcerative colitis had a Strongyloides infection and the organism was found in the fibrotic duct and pericholedochal lymph nodes. The etiological considerations are reviewed and the classification of sclerosing cholangitis associated with ulcerative colitis, as primary, is discussed. Therapeutic modalities are discussed, though therapy is mainly empirical at present.", "contents": "Primary sclerosing cholangitis. A report of nine cases and clinical review. Nine cases of primary sclerosing cholangitis were reviewed as to methods of diagnosis, association with other disease states and clinical course of the patients. There were four cases of primary sclerosing cholangitis occurring alone, four cases associated with inflammatory bowel disease (three with chronic ulcerative colitis and one case with proctosigmoiditis) and one case associated with porphyria cutanea tarda. All cases of primary sclerosing cholangitis occurring alone, progressed to secondary biliary cirrhosis, however, none of the cases associated with chronic ulcerative colitis progressed to secondary biliary cirrhosis. In all cases, the diagnosis was established by operative findings and biopsy results. The mode of clinical presentation was similar in all cases and was characterized by slowly progressive jaundice. Intravenous and oral cholangiography were not useful in establishing a diagnosis but endoscopic retrograde cholangiography offers preoperative diagnostic hope and use for follow-up evaluation. One case with ulcerative colitis had a Strongyloides infection and the organism was found in the fibrotic duct and pericholedochal lymph nodes. The etiological considerations are reviewed and the classification of sclerosing cholangitis associated with ulcerative colitis, as primary, is discussed. Therapeutic modalities are discussed, though therapy is mainly empirical at present."} {"id": "PMID:1274937", "title": "Precipitous rise and fall of SGOT.", "content": "Three patients are reported whose studies showed a transient but marked elevation of serum transaminase levels with a rapid return toward normal. In two patients this phenomenon was associated with transient episode of hypotension; in the third case this was an incidental finding discovered fortuitously on a routine test. Hepatic ischemia and parenchymal injury may cause transient elevations of serum transaminase levels.", "contents": "Precipitous rise and fall of SGOT. Three patients are reported whose studies showed a transient but marked elevation of serum transaminase levels with a rapid return toward normal. In two patients this phenomenon was associated with transient episode of hypotension; in the third case this was an incidental finding discovered fortuitously on a routine test. Hepatic ischemia and parenchymal injury may cause transient elevations of serum transaminase levels."} {"id": "PMID:1274938", "title": "Liver tests, HB-Ag and HB-Ab in asymptomatic drug addicts.", "content": "One hundred eighty-eight asymptomatic addicts were studied to determine the frequency of a history of hepatitis (previous episodes of jaundice), abnormalities of liver tests (serum bilirubin, alkaline phosphatase, serum albumin, serum glutamic oxalacetic transaminase) and incidence of HB-Ag and HB-Ab. Seventy-four were white and 114 were nonwhite. A history of hepatitis was obtained in only 38%. One hundred and fifty-two of the 188 addicts (81%) had one or more abnormal liver tests. The bilirubin was abnormal in 5%, akkaline phosphatase in 28% and serum glutamic oxalacetic transaminase in 55%. HB-Ag was positive in 2.6% using radioimmunoassay and HB-Ab was found in 66%. There was a higher incidence of elevated serum glutamic oxalacetic transaminase, HB-Ab and history of hepatitis among white, compared to nonwhite addicts.", "contents": "Liver tests, HB-Ag and HB-Ab in asymptomatic drug addicts. One hundred eighty-eight asymptomatic addicts were studied to determine the frequency of a history of hepatitis (previous episodes of jaundice), abnormalities of liver tests (serum bilirubin, alkaline phosphatase, serum albumin, serum glutamic oxalacetic transaminase) and incidence of HB-Ag and HB-Ab. Seventy-four were white and 114 were nonwhite. A history of hepatitis was obtained in only 38%. One hundred and fifty-two of the 188 addicts (81%) had one or more abnormal liver tests. The bilirubin was abnormal in 5%, akkaline phosphatase in 28% and serum glutamic oxalacetic transaminase in 55%. HB-Ag was positive in 2.6% using radioimmunoassay and HB-Ab was found in 66%. There was a higher incidence of elevated serum glutamic oxalacetic transaminase, HB-Ab and history of hepatitis among white, compared to nonwhite addicts."} {"id": "PMID:1274939", "title": "Hepatitis B-antigen subtypes in Australia as detected by radioimmunoassay.", "content": "The distribution of the major subtypes of hepatitis B surface antigen (HBsAg) was examined in asymptomatic white Australian blood donors and patients with liver disease to attempt ot assess the biological significance of these subtypes in this relatively homogeneous Caucasian population. Since previous studies have shown a very low prevalence of HBsAg in white Australians, a highly sensitive solid phase radioimmunoassay (RIA) was developed and used to subtype the antigen. A total of 46 samples of hepatitis B-antigen positive sera, obtained from 21 asymptomatic volunteer blood donors and 25 patients with liver disease, were tested. Sixteen of these 21 asymptomatic carriers were shown to have subtype \"ad\" whereas only seven of the patients with liver disease had this subtype. This difference was significant (P less than 0.005) and supports the view that subtype \"ad\" is associated with a carrier state and subtype \"ay\" with liver disease in Australia.", "contents": "Hepatitis B-antigen subtypes in Australia as detected by radioimmunoassay. The distribution of the major subtypes of hepatitis B surface antigen (HBsAg) was examined in asymptomatic white Australian blood donors and patients with liver disease to attempt ot assess the biological significance of these subtypes in this relatively homogeneous Caucasian population. Since previous studies have shown a very low prevalence of HBsAg in white Australians, a highly sensitive solid phase radioimmunoassay (RIA) was developed and used to subtype the antigen. A total of 46 samples of hepatitis B-antigen positive sera, obtained from 21 asymptomatic volunteer blood donors and 25 patients with liver disease, were tested. Sixteen of these 21 asymptomatic carriers were shown to have subtype \"ad\" whereas only seven of the patients with liver disease had this subtype. This difference was significant (P less than 0.005) and supports the view that subtype \"ad\" is associated with a carrier state and subtype \"ay\" with liver disease in Australia."} {"id": "PMID:1274940", "title": "Clinical observations on the biliary system in cystic fibrosis.", "content": "The biliary tree of 66 patients with cystic fibrosis was examined by conventional roentgenographic methods. Forty-five per cent of the oral cholecystograms were judged abnormal by our criteria. A study was considered abnormal if there was no visualization or if there was visualization of a microgallbladder or structural abnormality including marginal irregularities, septate gallbladder or cholelithiasis. Intravenous cholangiography was used to further study the 22 patients who did not visualize on the oral study. Again, anatomic abnormalities were prevalent but six patients in this group had normal appearing gallbladders. Abdominal pain, a frequent symptom in cystic fibrosis, was not associated with roentgenographic abnormality. No correlation was seen between the external biliary tree abnormalities and multifocal biliary cirrhosis which was present in 40% of these patients. Further, no correlation was seen between serum gamma glutamyl transpeptidase levels and either of these lesions.", "contents": "Clinical observations on the biliary system in cystic fibrosis. The biliary tree of 66 patients with cystic fibrosis was examined by conventional roentgenographic methods. Forty-five per cent of the oral cholecystograms were judged abnormal by our criteria. A study was considered abnormal if there was no visualization or if there was visualization of a microgallbladder or structural abnormality including marginal irregularities, septate gallbladder or cholelithiasis. Intravenous cholangiography was used to further study the 22 patients who did not visualize on the oral study. Again, anatomic abnormalities were prevalent but six patients in this group had normal appearing gallbladders. Abdominal pain, a frequent symptom in cystic fibrosis, was not associated with roentgenographic abnormality. No correlation was seen between the external biliary tree abnormalities and multifocal biliary cirrhosis which was present in 40% of these patients. Further, no correlation was seen between serum gamma glutamyl transpeptidase levels and either of these lesions."} {"id": "PMID:1274941", "title": "Relation of exocrine pancreatic function to the diameter of the pancreatic and common bile ducts.", "content": "One hundred and thirty-nine patients were examined for possible chronic pancreatitis by means of both pancreozymin-secretin test and endoscopic pancreatography of pancreatocholangiography. Pancreatic function as assessed by the pancreozymin-secretin test was impaired in 89 (64%) of the entire group. No significant relationship was demonstrated between pancreatic secretion of fluid, bicarbonate and amylase and the diameter of main pancreatic duct in both the entire group of the subgroup of patients with pancreatic dysfunction. On pancreatogram no gross morphological abnormalities were found in a high proportion of patients whose pancreatic function was impaired in minimal to moderate degree. There was a significant linear correlation between the diameters of the main pancreatic duct and common bile duct. These data question the value of endoscopic pancreatography in the diagnosis of low to moderate grade chronic pancreatitis.", "contents": "Relation of exocrine pancreatic function to the diameter of the pancreatic and common bile ducts. One hundred and thirty-nine patients were examined for possible chronic pancreatitis by means of both pancreozymin-secretin test and endoscopic pancreatography of pancreatocholangiography. Pancreatic function as assessed by the pancreozymin-secretin test was impaired in 89 (64%) of the entire group. No significant relationship was demonstrated between pancreatic secretion of fluid, bicarbonate and amylase and the diameter of main pancreatic duct in both the entire group of the subgroup of patients with pancreatic dysfunction. On pancreatogram no gross morphological abnormalities were found in a high proportion of patients whose pancreatic function was impaired in minimal to moderate degree. There was a significant linear correlation between the diameters of the main pancreatic duct and common bile duct. These data question the value of endoscopic pancreatography in the diagnosis of low to moderate grade chronic pancreatitis."} {"id": "PMID:1274942", "title": "Liver actinomycosis: a case report.", "content": "A case of liver actinomycosis successfully treated with high doses of penicillin for a long period after surgery is reported. The unusual location of the disease and early detection difficulties delayed the diagnosis and establishment of proper treatment, causing additional liver damage. Serum globulin levels, alkaline phosphatase and turbidity tests were of diagnostic significance. Adequate drainage of the lesion and long-term antibiotic treatment with penicillin proved therapeutically satisfactory.", "contents": "Liver actinomycosis: a case report. A case of liver actinomycosis successfully treated with high doses of penicillin for a long period after surgery is reported. The unusual location of the disease and early detection difficulties delayed the diagnosis and establishment of proper treatment, causing additional liver damage. Serum globulin levels, alkaline phosphatase and turbidity tests were of diagnostic significance. Adequate drainage of the lesion and long-term antibiotic treatment with penicillin proved therapeutically satisfactory."} {"id": "PMID:1274944", "title": "Pruritus of pregnancy and jaundice induced by oral contraceptives.", "content": "This article presents a young girl who developed jaundice while on oral contraceptives. A most significant feature in this particular patient's history was the severe pruritus she developed during a previous gestation. This combination of events should alert physicians to the possible diagnosis. Oral contraceptives should be prescribed to such a patient with great caution.", "contents": "Pruritus of pregnancy and jaundice induced by oral contraceptives. This article presents a young girl who developed jaundice while on oral contraceptives. A most significant feature in this particular patient's history was the severe pruritus she developed during a previous gestation. This combination of events should alert physicians to the possible diagnosis. Oral contraceptives should be prescribed to such a patient with great caution."} {"id": "PMID:1274945", "title": "The jejunal mucosa in two cases of A-beta-lipoproteinemia.", "content": "The jejunal biopsy appearances in two cases of a-beta-lipoproteinemia are described and compared with those of previous cases recorded in the literature. No significant differences were noted in one of the cases in the appearances of a biopsy taken before and another taken after 10 months of treatment.", "contents": "The jejunal mucosa in two cases of A-beta-lipoproteinemia. The jejunal biopsy appearances in two cases of a-beta-lipoproteinemia are described and compared with those of previous cases recorded in the literature. No significant differences were noted in one of the cases in the appearances of a biopsy taken before and another taken after 10 months of treatment."} {"id": "PMID:1274946", "title": "Polyposis coli associated with fibrosis of mesentery, mesocolon and retroperitoneal tissues: a rare variant of Gardner's syndrome.", "content": "The association of polyposis coli, osseous and dental abnormalities with fibrosis of mesentery, mesocolon and retroperitoneal tissues is described in a black male. The prognostic significance of this association, rendering colectomy impossible, is stressed.", "contents": "Polyposis coli associated with fibrosis of mesentery, mesocolon and retroperitoneal tissues: a rare variant of Gardner's syndrome. The association of polyposis coli, osseous and dental abnormalities with fibrosis of mesentery, mesocolon and retroperitoneal tissues is described in a black male. The prognostic significance of this association, rendering colectomy impossible, is stressed."} {"id": "PMID:1274947", "title": "Cholecystoenteric fistulas:s ignificance and radiographic diagnosis.", "content": "Cholecystoenteric fistulas, not associated with gallstone ileus syndrome, are relatively common complications occurring during the natural history of cholelithiasis and cholecystitis. The etiology, pathogenesis as well as common and uncommon forms of gallbladder fistulas are presented and discussed. The roentgenographic findings are reviewed and a simple classification into two major groups is offered. The majority are acute, transitory, short-lived fistulas, which are self-limiting and relatively common events that usually remain undiagnosed. A minority fail to heal, become chronic and permanent fistulas and are associated with obstruction of the common duct.", "contents": "Cholecystoenteric fistulas:s ignificance and radiographic diagnosis. Cholecystoenteric fistulas, not associated with gallstone ileus syndrome, are relatively common complications occurring during the natural history of cholelithiasis and cholecystitis. The etiology, pathogenesis as well as common and uncommon forms of gallbladder fistulas are presented and discussed. The roentgenographic findings are reviewed and a simple classification into two major groups is offered. The majority are acute, transitory, short-lived fistulas, which are self-limiting and relatively common events that usually remain undiagnosed. A minority fail to heal, become chronic and permanent fistulas and are associated with obstruction of the common duct."} {"id": "PMID:1274949", "title": "Estrogen use and stroke risk in postmenopausal women.", "content": "Among postmenopausal women (58-98 years of age) in a retirement community use of oral estrogens was not significantly associated with overall risk of stroke. Estrogen use was significantly associated with blood-pressure status. An observed association between estrogen use and nonembolic cerebral infarction in women aged 70-79 may be secondary to an interaction between hypertension and estrogen usage.", "contents": "Estrogen use and stroke risk in postmenopausal women. Among postmenopausal women (58-98 years of age) in a retirement community use of oral estrogens was not significantly associated with overall risk of stroke. Estrogen use was significantly associated with blood-pressure status. An observed association between estrogen use and nonembolic cerebral infarction in women aged 70-79 may be secondary to an interaction between hypertension and estrogen usage."} {"id": "PMID:1274950", "title": "Aggregation of blood pressure in infants and their siblings.", "content": "Sibling aggregation of blood pressure has been shown in children 2 to 14 years of age. To determine the earliest age at which this finding is detectable, blood pressures were evaluated in 98 siblings from 43 black families with newborns. Variances of blood pressure scores were significantly greater among families than within families for systolic (p less than .025) but not diastolic pressures. Sib-sib intraclass correlation coefficients were .26 (95% two-sided confidence limits .05 to .47) for systolic and .16 (-.06 to .38) for diastolic pressures. When 1-month-old infant pressures were added, significant aggregation was present for systolic (p less than .01) and diastolic (p less than .025) pressures. The intraclass correlation coefficients were .21 (.02 to .38) and .17 (.03 to .34), respectively. When newborn scores were substituted, aggregation was not demonstrable. These data demonstrate a familial influence on blood pressure in infancy by 1 month of age.", "contents": "Aggregation of blood pressure in infants and their siblings. Sibling aggregation of blood pressure has been shown in children 2 to 14 years of age. To determine the earliest age at which this finding is detectable, blood pressures were evaluated in 98 siblings from 43 black families with newborns. Variances of blood pressure scores were significantly greater among families than within families for systolic (p less than .025) but not diastolic pressures. Sib-sib intraclass correlation coefficients were .26 (95% two-sided confidence limits .05 to .47) for systolic and .16 (-.06 to .38) for diastolic pressures. When 1-month-old infant pressures were added, significant aggregation was present for systolic (p less than .01) and diastolic (p less than .025) pressures. The intraclass correlation coefficients were .21 (.02 to .38) and .17 (.03 to .34), respectively. When newborn scores were substituted, aggregation was not demonstrable. These data demonstrate a familial influence on blood pressure in infancy by 1 month of age."} {"id": "PMID:1274951", "title": "Changing risks in tuberculosis.", "content": "Past and present experience with tuberculosis in New York State exclusive of New York City is presented. TB has been on the decline since the turn of the century and reached an all-time low in 1974 with only 844 new active cases and 137 deaths reported. Although incidence rates are highest among the poor, the bulk of cases come from middle and upper socioeconomic levels. Cohort analysis shows an individual's risk of developing pulmonary or miliary TB is greatest at age 20-24, whereas the greatest risk of dying from TB is before age 5. Projections based on past experience indicate a male born in 1970-74 will have a lifetime risk of developing pulmonary or miliary TB of 80/100,000 and of dying from TB of 4/100,000. For females the respective risks are 40/100,000 and 6/100,000.", "contents": "Changing risks in tuberculosis. Past and present experience with tuberculosis in New York State exclusive of New York City is presented. TB has been on the decline since the turn of the century and reached an all-time low in 1974 with only 844 new active cases and 137 deaths reported. Although incidence rates are highest among the poor, the bulk of cases come from middle and upper socioeconomic levels. Cohort analysis shows an individual's risk of developing pulmonary or miliary TB is greatest at age 20-24, whereas the greatest risk of dying from TB is before age 5. Projections based on past experience indicate a male born in 1970-74 will have a lifetime risk of developing pulmonary or miliary TB of 80/100,000 and of dying from TB of 4/100,000. For females the respective risks are 40/100,000 and 6/100,000."} {"id": "PMID:1274953", "title": "Effect of a mass screening program on the risk of cervical cancer.", "content": "In Finland, the organized mass screening program for the early detection of cervical cancer covers, with few exceptions, all women between the ages of 30 and 55 every fifth year. On the basis of material originating from the Finnish Cancer Registry it was estimated that the probability for a woman aged 30-59 to experience frankly invasive cervical cancer was 0.010 before the screening program, and 0.002 after the first screening. The corresponding probability estimate was 0.022 for pre-invasive lesions subjected to operative treatment. On the assumption that the same relationship applies beyond this age group it was estimated that from 28-39% of the pre-invasive cases progress to invasive cervical cancer, and that 21% of the frankly invasive cases are preceded by a pre-invasive stage of shorter duration than the time period between the screenings, or have no preclinical stage.", "contents": "Effect of a mass screening program on the risk of cervical cancer. In Finland, the organized mass screening program for the early detection of cervical cancer covers, with few exceptions, all women between the ages of 30 and 55 every fifth year. On the basis of material originating from the Finnish Cancer Registry it was estimated that the probability for a woman aged 30-59 to experience frankly invasive cervical cancer was 0.010 before the screening program, and 0.002 after the first screening. The corresponding probability estimate was 0.022 for pre-invasive lesions subjected to operative treatment. On the assumption that the same relationship applies beyond this age group it was estimated that from 28-39% of the pre-invasive cases progress to invasive cervical cancer, and that 21% of the frankly invasive cases are preceded by a pre-invasive stage of shorter duration than the time period between the screenings, or have no preclinical stage."} {"id": "PMID:1274959", "title": "Limitations of compounding diazepam suspensions from tablets.", "content": "The concentration of diazepam in two types of suspension vehicles, as prepared from 10-mg tablets was tested over a 14-day period. The suspensions (1 mg/ml) were stored at room temperature in amber glass bottles. In one suspension, consisting of eight triturated tablets, 4.0 ml ethanol, 24.0 ml propylene glycol, 20.0 ml Syrup, USP, and 32.0 ml chocolate syrup, 90% of the diazepam was dissolved. This suspension demonstrated consistently acceptable concentrations of diazepam. In the other suspension, consisting of triturated tablets and Syrup, USP, only 25% of the diazepam was dissolved, and less consistent, subpotent concentrations of diazepam were found. The variation of diazepam concentrations between the suspensions was unrelated to the chemical stability of the drug.", "contents": "Limitations of compounding diazepam suspensions from tablets. The concentration of diazepam in two types of suspension vehicles, as prepared from 10-mg tablets was tested over a 14-day period. The suspensions (1 mg/ml) were stored at room temperature in amber glass bottles. In one suspension, consisting of eight triturated tablets, 4.0 ml ethanol, 24.0 ml propylene glycol, 20.0 ml Syrup, USP, and 32.0 ml chocolate syrup, 90% of the diazepam was dissolved. This suspension demonstrated consistently acceptable concentrations of diazepam. In the other suspension, consisting of triturated tablets and Syrup, USP, only 25% of the diazepam was dissolved, and less consistent, subpotent concentrations of diazepam were found. The variation of diazepam concentrations between the suspensions was unrelated to the chemical stability of the drug."} {"id": "PMID:1274960", "title": "Operations analysis applied to a drug distribution system.", "content": "The application of operations analysis to a hospital drug distribution system is discussed. The existing system in a 360-bed community hospital was reviewed to identify areas for improvement; alternate approaches to achieve the identified benefits were explored. Improved manual procedures, which integrated pharmacy and nursing operations to a greater extent and resulted in fewer lost charges, were developed. Potential savings through computerization of 10 functions were identified. A rating system was developed to evaluate eight vendors of computerized pharmacy systems. The hospital as a whole undertook the following steps designed to assure the success of new systems: (1) determine the overall hospital benefits desired in order to prevent fragmentation by individual efforts; (2) establish a planning process; (3) establish a process for reviewing projects; (4) develop a plan for systems improvement; and (5) monitor the performance of the systems improvement program. The steps for successful operations analysis are summarized.", "contents": "Operations analysis applied to a drug distribution system. The application of operations analysis to a hospital drug distribution system is discussed. The existing system in a 360-bed community hospital was reviewed to identify areas for improvement; alternate approaches to achieve the identified benefits were explored. Improved manual procedures, which integrated pharmacy and nursing operations to a greater extent and resulted in fewer lost charges, were developed. Potential savings through computerization of 10 functions were identified. A rating system was developed to evaluate eight vendors of computerized pharmacy systems. The hospital as a whole undertook the following steps designed to assure the success of new systems: (1) determine the overall hospital benefits desired in order to prevent fragmentation by individual efforts; (2) establish a planning process; (3) establish a process for reviewing projects; (4) develop a plan for systems improvement; and (5) monitor the performance of the systems improvement program. The steps for successful operations analysis are summarized."} {"id": "PMID:1274961", "title": "Computerized pharmacy services in a large community hospital.", "content": "A computerized pharmacy system dealing with drug distribution, clinical services and administrative services is described. Present systems, implemented for 50% of the institution's beds, are discussed fully. Future applications of the system are outlined.", "contents": "Computerized pharmacy services in a large community hospital. A computerized pharmacy system dealing with drug distribution, clinical services and administrative services is described. Present systems, implemented for 50% of the institution's beds, are discussed fully. Future applications of the system are outlined."} {"id": "PMID:1274962", "title": "Current federal legislation.", "content": "Current legislative proposals before Congress that will affect the practice of pharmacy are discussed. Revisions to the Medicare and Medicaid programs and amendment of the HMO Act of 1974 are being considered. Major legislation includes a bill that will regulate the activities of clinical laboratories and a bill that establishes a Presidential commission to oversee biomedical and behavioral research. Also proposed is a reorganization of the FDA which would create a new agency to assume responsibility for scientific and enforcement duties related to drugs and devices. Regulation of vitamins, health manpower and drug utilization improvement are also discussed.", "contents": "Current federal legislation. Current legislative proposals before Congress that will affect the practice of pharmacy are discussed. Revisions to the Medicare and Medicaid programs and amendment of the HMO Act of 1974 are being considered. Major legislation includes a bill that will regulate the activities of clinical laboratories and a bill that establishes a Presidential commission to oversee biomedical and behavioral research. Also proposed is a reorganization of the FDA which would create a new agency to assume responsibility for scientific and enforcement duties related to drugs and devices. Regulation of vitamins, health manpower and drug utilization improvement are also discussed."} {"id": "PMID:1274963", "title": "Tardive dyskinesia.", "content": "The etiology, pharmacology, treatment and possible prevention of tardive dyskinesia (TD) are discussed. This neurological disorder, characterized by involuntary movements of the lips, jaws and tongue, can occur as a result of short-term antipsychotic drug therapy, but usually occurs after long-term treatment. Phenothiazines, the thioxanthines, butyrophenones, dibenzoxazepines and dihydroindolines also posess the potential for inducing TD. Methods of treatment of TD with dopamine-depleting agents, dopamine-blocking agents and cholinomimetics are discussed. Despite the apparent effectiveness of some drugs in the treatment of TD, it should be kept in mind that most of the studies demonstrating drug effectiveness involved a small number of patients.", "contents": "Tardive dyskinesia. The etiology, pharmacology, treatment and possible prevention of tardive dyskinesia (TD) are discussed. This neurological disorder, characterized by involuntary movements of the lips, jaws and tongue, can occur as a result of short-term antipsychotic drug therapy, but usually occurs after long-term treatment. Phenothiazines, the thioxanthines, butyrophenones, dibenzoxazepines and dihydroindolines also posess the potential for inducing TD. Methods of treatment of TD with dopamine-depleting agents, dopamine-blocking agents and cholinomimetics are discussed. Despite the apparent effectiveness of some drugs in the treatment of TD, it should be kept in mind that most of the studies demonstrating drug effectiveness involved a small number of patients."} {"id": "PMID:1274964", "title": "Management of insulin allergy and resistance.", "content": "The pathophysiologic basis and therapy of insulin insensitivity and insulin allergy are discussed. Topics covered include primary and secondary causes of insulin insensitivity, management of insulin resistance (elimination of diabetogenic factors; use of less antigenic insulin, oral hypoglycemic agents, immunosuppression, or nonmammalian insulin), and insulin allergy and its treatment. A pharmacist's knowledge of insulin products and the pharmacologic activity of the oral hypoglycemic and immunosuppressive agents may aid in the care of patients who are allergic or resistant to insulin.", "contents": "Management of insulin allergy and resistance. The pathophysiologic basis and therapy of insulin insensitivity and insulin allergy are discussed. Topics covered include primary and secondary causes of insulin insensitivity, management of insulin resistance (elimination of diabetogenic factors; use of less antigenic insulin, oral hypoglycemic agents, immunosuppression, or nonmammalian insulin), and insulin allergy and its treatment. A pharmacist's knowledge of insulin products and the pharmacologic activity of the oral hypoglycemic and immunosuppressive agents may aid in the care of patients who are allergic or resistant to insulin."} {"id": "PMID:1274971", "title": "Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 2: stability with some commonly used antibiotics in 5% dextrose injection.", "content": "The stability of dopamine hydrochloride (Intropin) and several commonly used antibiotics was studied as admixtures in 5% Dextrose Injection USP. The antibiotic-dopamine-dextrose 5% admixtures were assayed for dopamine by colorimetric and chromatographic procedures. The antibiotics were assayed by standard microbiological methods. Kanamycin sulfate, tetracycline hydrochloride, carbenicillin disodium and chloramphenicol sodium succinate were stable in the Intropin-5% dextrose admixture for a period of 24 hours at room temperature in fluorescent and natural (western exposure) light. Gentamicin sulfate, penicillin G potassium and cephalothin sodium were stable in Intropin-5% dextrose admixture for six hours. Ampicillin sodium was stable in the Intropin admixture for only one hour. Amphotericin B was physically unstable in the Intropin-dextrose 5% solution upon admixture. The potency of dopamine hydrochloride remained substantially unchanged in the presence of the above antibiotics. It is recommended that dopamine not be added to amphotericin B or ampicillin sodium admixtures. Further, in order to avoid a fixed combination of potent drugs, it is recommended that a \"piggyback\" administration set or administration into a second injection site be employed when another drug is to be administered with dopamine hydrochloride.", "contents": "Intropin (dopamine hydrochloride) intravenous admixture compatibility. Part 2: stability with some commonly used antibiotics in 5% dextrose injection. The stability of dopamine hydrochloride (Intropin) and several commonly used antibiotics was studied as admixtures in 5% Dextrose Injection USP. The antibiotic-dopamine-dextrose 5% admixtures were assayed for dopamine by colorimetric and chromatographic procedures. The antibiotics were assayed by standard microbiological methods. Kanamycin sulfate, tetracycline hydrochloride, carbenicillin disodium and chloramphenicol sodium succinate were stable in the Intropin-5% dextrose admixture for a period of 24 hours at room temperature in fluorescent and natural (western exposure) light. Gentamicin sulfate, penicillin G potassium and cephalothin sodium were stable in Intropin-5% dextrose admixture for six hours. Ampicillin sodium was stable in the Intropin admixture for only one hour. Amphotericin B was physically unstable in the Intropin-dextrose 5% solution upon admixture. The potency of dopamine hydrochloride remained substantially unchanged in the presence of the above antibiotics. It is recommended that dopamine not be added to amphotericin B or ampicillin sodium admixtures. Further, in order to avoid a fixed combination of potent drugs, it is recommended that a \"piggyback\" administration set or administration into a second injection site be employed when another drug is to be administered with dopamine hydrochloride."} {"id": "PMID:1274972", "title": "Particulate matter assessment of a clinical investigation on filtration and infusion phlebitis.", "content": "Particulate contamination levels of a base intravenous solution and five admixtures were assessed in a double-blind study conducted to determine the effect of inline i.v. filtration on infusion phlebitis. Only a qualitative evaluation on actual patient filters was possible due to deformation of the filter membrane after 72 hours; simulation of i.v. therapy in the laboratory gave more reliable information about particle counts and distribution. The base solution was dextrose 5% in 0.2% sodium chloride injection; the admixtures contained this base solution and the following additives (per liter): (1) 20 mEq potassium chloride, (2) 20 mEq potassium chloride and 2 ml vitamin B complex, (3) 20 mEq potassium chloride and 5 million units of potassium penicillin G, (4) 20 mEq potassium chloride and 1 g cephalothin sodium (delivered in a 100-ml volume from a medication chamber), and (5) 30 mEq potassium chloride and 3 million units of penicillin G (delivered every four hours from a medication chamber) and 80 mg of gentamicin sulfate (delivered every eight hours from a medication chamber). None of the six i.v. infusion schedules simulated exceeded the standards for particulate matter prescribed by the USP XIX. As expected, however, the particle counts increased as a function of the additives used in the simulation, particularly with the antibiotics.", "contents": "Particulate matter assessment of a clinical investigation on filtration and infusion phlebitis. Particulate contamination levels of a base intravenous solution and five admixtures were assessed in a double-blind study conducted to determine the effect of inline i.v. filtration on infusion phlebitis. Only a qualitative evaluation on actual patient filters was possible due to deformation of the filter membrane after 72 hours; simulation of i.v. therapy in the laboratory gave more reliable information about particle counts and distribution. The base solution was dextrose 5% in 0.2% sodium chloride injection; the admixtures contained this base solution and the following additives (per liter): (1) 20 mEq potassium chloride, (2) 20 mEq potassium chloride and 2 ml vitamin B complex, (3) 20 mEq potassium chloride and 5 million units of potassium penicillin G, (4) 20 mEq potassium chloride and 1 g cephalothin sodium (delivered in a 100-ml volume from a medication chamber), and (5) 30 mEq potassium chloride and 3 million units of penicillin G (delivered every four hours from a medication chamber) and 80 mg of gentamicin sulfate (delivered every eight hours from a medication chamber). None of the six i.v. infusion schedules simulated exceeded the standards for particulate matter prescribed by the USP XIX. As expected, however, the particle counts increased as a function of the additives used in the simulation, particularly with the antibiotics."} {"id": "PMID:1274973", "title": "Compliance with USP osmolarity labeling requirements.", "content": "In view of the USP requirement that the label of certain parenteral products contain the osmolarity of the solution, actual and theoretical osmolarity values for six preparations were determined, and the extent of any deviation was noted. Osmolarity values were determined experimentally by osmometry and converted to osmolarity values for six products: Calcium Chloride Injection USP, Dextrose Injection USP, Mannitol Injection USP, Potassium Chloride Injection USP, Sodium Bicarbonate Injection USP, and Sodium Chloride Injection USP. Theoretical values were calculated according to a standard equation based on the mass of the substance per liter of solution. The most substantial deviations between actual and theoretical osmolarity values occurred with the calcium chloride, sodium bicarbonate, potassium chloride and dextrose solutions. It is proposed that the technology for making osmotic measurements which exists in the industrial setting should be used to provide clinical practitioners with accurate and actual values. It is also urged that the USP specify a procedure for measuring osmolality and calculating actual osmolarity.", "contents": "Compliance with USP osmolarity labeling requirements. In view of the USP requirement that the label of certain parenteral products contain the osmolarity of the solution, actual and theoretical osmolarity values for six preparations were determined, and the extent of any deviation was noted. Osmolarity values were determined experimentally by osmometry and converted to osmolarity values for six products: Calcium Chloride Injection USP, Dextrose Injection USP, Mannitol Injection USP, Potassium Chloride Injection USP, Sodium Bicarbonate Injection USP, and Sodium Chloride Injection USP. Theoretical values were calculated according to a standard equation based on the mass of the substance per liter of solution. The most substantial deviations between actual and theoretical osmolarity values occurred with the calcium chloride, sodium bicarbonate, potassium chloride and dextrose solutions. It is proposed that the technology for making osmotic measurements which exists in the industrial setting should be used to provide clinical practitioners with accurate and actual values. It is also urged that the USP specify a procedure for measuring osmolality and calculating actual osmolarity."} {"id": "PMID:1274974", "title": "ABC inventory analysis and economic order quantity concept in hospital pharmacy purchasing.", "content": "ABC inventory analysis and the economic order quantity (EOQ) concept were studied as alternatives to the cyclical ordering system used by the pharmacy in a 558-bed general hospital. The inventory was divided into A, B or C groups according to the annual dollar value of the items. Two samples were selected to be studied (the first consisting of 10% of the total inventory and the second consisting of 10% of the A, or high cost, items). For each item in both samples the EOQ was calculated to estimate the proposed annual inventory cost as compared to the actual cost as determined from past inventory records. In the first sample, there was a statistically significant mean annual savings of $4.13 +/- $0.36 (S.E.) using the proposed annual cost. In the second sample there was a mean savings of $2.42 +/- $0.60 (S.E.) using the proposed method, which was not statistically significant. Most of the savings with the proposed ABC-EOQ system would occur with the low dollar value items (B and C items) which were being purchased too frequently.", "contents": "ABC inventory analysis and economic order quantity concept in hospital pharmacy purchasing. ABC inventory analysis and the economic order quantity (EOQ) concept were studied as alternatives to the cyclical ordering system used by the pharmacy in a 558-bed general hospital. The inventory was divided into A, B or C groups according to the annual dollar value of the items. Two samples were selected to be studied (the first consisting of 10% of the total inventory and the second consisting of 10% of the A, or high cost, items). For each item in both samples the EOQ was calculated to estimate the proposed annual inventory cost as compared to the actual cost as determined from past inventory records. In the first sample, there was a statistically significant mean annual savings of $4.13 +/- $0.36 (S.E.) using the proposed annual cost. In the second sample there was a mean savings of $2.42 +/- $0.60 (S.E.) using the proposed method, which was not statistically significant. Most of the savings with the proposed ABC-EOQ system would occur with the low dollar value items (B and C items) which were being purchased too frequently."} {"id": "PMID:1274975", "title": "Alpha-methyldopa interference with the phosphotungstate uric acid test.", "content": "The effect of alpha-methyldopa on the phosphotungstate method of uric acid analysis was tested using a group of 17 hypertensive patients being treated with only this drug for their elevated blood pressure. The uric acid values of these patients tested by the phosphotungstate method showed no significant difference from the uricase test values, when compared to a control population of 32 normotensive patients tested in the same manner. The proposed interference was further tested by in vitro studies. Both uricase and phosphotungstate analysis of uric acid was performed on serum containing various dilutions of alpha-methyldopa. The concentration of alpha-methyldopa required to clinically affect the uric acid level, whereby a false positive result occurred, was 60 mug/ml. The mean plasma aplha-methyldopa concentration in the study group, however, was found to be only 2.03 mug/ml. The postulated interference of therapeutic levels of alpha-methyldopa on the phosphotungstate uric acid method was invalid.", "contents": "Alpha-methyldopa interference with the phosphotungstate uric acid test. The effect of alpha-methyldopa on the phosphotungstate method of uric acid analysis was tested using a group of 17 hypertensive patients being treated with only this drug for their elevated blood pressure. The uric acid values of these patients tested by the phosphotungstate method showed no significant difference from the uricase test values, when compared to a control population of 32 normotensive patients tested in the same manner. The proposed interference was further tested by in vitro studies. Both uricase and phosphotungstate analysis of uric acid was performed on serum containing various dilutions of alpha-methyldopa. The concentration of alpha-methyldopa required to clinically affect the uric acid level, whereby a false positive result occurred, was 60 mug/ml. The mean plasma aplha-methyldopa concentration in the study group, however, was found to be only 2.03 mug/ml. The postulated interference of therapeutic levels of alpha-methyldopa on the phosphotungstate uric acid method was invalid."} {"id": "PMID:1274976", "title": "Portland Retail Druggists Association vs Abbott Laboratories et al, part 1.", "content": "The findings of the U.S. Supreme Court, in its March 24, 1976, decision in the case of Portland Retail Druggists vs Abbott Laboratories et al, are presented. The case deals with price differentials offered to nonprofit hospitals by pharmaceutical manufacturers. Historical background leading to the case, and early rulings of a federal district court and a court of appeals, are discussed. The Supreme Court decision appears to reflect favorably on current hospital policies and procedures for drug purchasing and ambulatory care. Issues that require further clarification will be discussed in Part 2.", "contents": "Portland Retail Druggists Association vs Abbott Laboratories et al, part 1. The findings of the U.S. Supreme Court, in its March 24, 1976, decision in the case of Portland Retail Druggists vs Abbott Laboratories et al, are presented. The case deals with price differentials offered to nonprofit hospitals by pharmaceutical manufacturers. Historical background leading to the case, and early rulings of a federal district court and a court of appeals, are discussed. The Supreme Court decision appears to reflect favorably on current hospital policies and procedures for drug purchasing and ambulatory care. Issues that require further clarification will be discussed in Part 2."} {"id": "PMID:1274977", "title": "Pharmacotherapy of cardiopulmonary arrest.", "content": "The assessment and treatment of patients requiring cardiopulmonary resuscitation (CPR) is discussed. Cardiovascular pharmacotherapy is discussed as suppressive therapy, stimulant therapy and treatment of hypotension. Special situations covered include hyperkalemia, anaphylaxis and drug overdosages. It is concluded that the likelihood of success of CPR depends on the rapid initiation of ventilation and restoration of circulation, and is inversely dependent on the severity of the underlying disease or injury.", "contents": "Pharmacotherapy of cardiopulmonary arrest. The assessment and treatment of patients requiring cardiopulmonary resuscitation (CPR) is discussed. Cardiovascular pharmacotherapy is discussed as suppressive therapy, stimulant therapy and treatment of hypotension. Special situations covered include hyperkalemia, anaphylaxis and drug overdosages. It is concluded that the likelihood of success of CPR depends on the rapid initiation of ventilation and restoration of circulation, and is inversely dependent on the severity of the underlying disease or injury."} {"id": "PMID:1274978", "title": "Potassium iodide and iododerma.", "content": "The development of iododerma in a 75-year-old male following administration of potassium iodide is described. Recovery from the allergic manifestation of iododerma occurred after discontinuation of potassium iodide. The adverse effects of potassium iodide and the general signs of acute and chronic iodine toxicity are reviewed.", "contents": "Potassium iodide and iododerma. The development of iododerma in a 75-year-old male following administration of potassium iodide is described. Recovery from the allergic manifestation of iododerma occurred after discontinuation of potassium iodide. The adverse effects of potassium iodide and the general signs of acute and chronic iodine toxicity are reviewed."} {"id": "PMID:1274981", "title": "Nationwide epidemic of septicemia caused by contaminated intravenous products. I. Epidemiologic and clinical features.", "content": "Between mid-1970 and April 1, 1971, Enterobacter cloacae or E. agglomerans septicemia developed in 378 patients in 25 American hospitals while they were receiving intravenous products manufactured by one company. Each of the hospitals noted a marked increase in the incidence of such septicemia during this period. Enterobacter agglomerans (formerly designated Erwinia, herbicola-lathyri group) was better known as a plant pathogen and had been a human blood pathogen only rarely in the past. Septicemia caused by E. cloacae had also been uncommon.", "contents": "Nationwide epidemic of septicemia caused by contaminated intravenous products. I. Epidemiologic and clinical features. Between mid-1970 and April 1, 1971, Enterobacter cloacae or E. agglomerans septicemia developed in 378 patients in 25 American hospitals while they were receiving intravenous products manufactured by one company. Each of the hospitals noted a marked increase in the incidence of such septicemia during this period. Enterobacter agglomerans (formerly designated Erwinia, herbicola-lathyri group) was better known as a plant pathogen and had been a human blood pathogen only rarely in the past. Septicemia caused by E. cloacae had also been uncommon."} {"id": "PMID:1274982", "title": "Selective immunoglobulin M (IgM) deficiency in two immunodeficient adults with recurrent staphylococcal pyoderma.", "content": "Two adult men with recurrent pyoderma due to Staphylococcus aureus and a selective deficiency of immunoglobulin M (IgM) antibody synthesis are described. An analysis of each patient's polymorphonuclear leukocyte chemotaxis, phagocytosis and killing of Staph. aureus, serum opsonizaiton of Staph. aureus, and serum and lymphocyte-mediated responses to antigenic stimulation was performed. Family studies revealed a possible autosomal dominant inheritance pattern with heterogenetic expression of various dysgammaglobulinemic states in each patient's first degree relatives. In vivo studies of delayed hypersensitivity and in vitro studies of polymorphonuclear leukocyte and lymphocyte function were normal. A defect in IgM, but not in IgG (immunoglobulin G), antibody synthesis to a number of antigens, and a mild decrease in serum opsonic activity to Staph. aureus correctable by heat inactivated normal human serum were found in each patient. In these patients, the recurrent staphulococcal pyoderma prompted an investigation of host defense mechanisms and revealed low to absent IgM levels and a defect in IgM antibody synthesis.", "contents": "Selective immunoglobulin M (IgM) deficiency in two immunodeficient adults with recurrent staphylococcal pyoderma. Two adult men with recurrent pyoderma due to Staphylococcus aureus and a selective deficiency of immunoglobulin M (IgM) antibody synthesis are described. An analysis of each patient's polymorphonuclear leukocyte chemotaxis, phagocytosis and killing of Staph. aureus, serum opsonizaiton of Staph. aureus, and serum and lymphocyte-mediated responses to antigenic stimulation was performed. Family studies revealed a possible autosomal dominant inheritance pattern with heterogenetic expression of various dysgammaglobulinemic states in each patient's first degree relatives. In vivo studies of delayed hypersensitivity and in vitro studies of polymorphonuclear leukocyte and lymphocyte function were normal. A defect in IgM, but not in IgG (immunoglobulin G), antibody synthesis to a number of antigens, and a mild decrease in serum opsonic activity to Staph. aureus correctable by heat inactivated normal human serum were found in each patient. In these patients, the recurrent staphulococcal pyoderma prompted an investigation of host defense mechanisms and revealed low to absent IgM levels and a defect in IgM antibody synthesis."} {"id": "PMID:1274983", "title": "Staphylococcus aureus bacteremia. Current clinical patterns.", "content": "One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics.", "contents": "Staphylococcus aureus bacteremia. Current clinical patterns. One hundred and five cases of bacteremia due to Staphylococcus aureus were reviewed to assess the current clinical spectrum of serious staphylococcal disease. Mortality was 21 percent, lower than previously reported. Patients could be separated into two groups according to the presence of identifiable primary staphylococcal infections; 63 bacteremic patients had such lesions, the remaining 42 lacked them. The latter group contained 24 of 26 cases of endocarditis. Illnesses in that group were marked by the presence (in 38 of 42 patients) of staphylococcal foci occurring secondary to bacteremia. Such foci were responsible for five of seven instances of relapse or treatment failure encountered in that group. Secondary staphylococcal foci occurred in only five of 63 patients with primary infections, and the response of this group to conventional therapy for bacteremia was satisfactory. This study suggests that endocarditis has become an unusual complication of identifiable primary staphylococcal infection. A clinical classification based on the presence of such lesions therefore separates bacteremic patients likely to be cured by conventional antibiotic therapy (those with primary infections but no secondary foci) from others (those with secondary foci, suggesting endocarditis) who should receive a more prolonged course of antibiotics."} {"id": "PMID:1274984", "title": "Salmonella heidelberg enteritis and bacteremia. An epidemic on two pediatric wards.", "content": "Symptomatic infection with Salmonella heidelberg developed in 55 children after their admission to the pediatric wards of two adjacent hospiatls in San Juan, Puerto Rico. Many of these children had been hospitalized for the treatment of diarrhea of unidentified etiology. In 25 of these patients, Salmonella bacteremia was documented. Five had clinically unsuspected and untreated bacteremia with no evidence of complications during the follow-up period of four and a half months. The remaining 30 had \"standard\" symptomatic infection due to S. heidelberg. Eight children died; four of these proved to be bacteremic. The index patient, who also introduced the infection into one of the hospitals, was identified. Person to person spread perpetuated the outbreak within and between the two hospitals for nearly four months. Although neonates with salmonellosis had a higher rate of bacteremia than other children, no other specific predisposing factors for Salmonella bacteremia were identified. Laboratory studies of the epidemic strain revealed neither invasive nor enterotoxic properties of the organisms, nor enhanced virulence in laboratory mice. Cohort nursing and isolation of patients with positive cultures halted the epidemic. Nontyphoid Salmonella bacteremia, sometimes clinically unsuspected and self-limited, should be recognized as a frequent accompaniment of Salmonella enteritis in young hospitalized children.", "contents": "Salmonella heidelberg enteritis and bacteremia. An epidemic on two pediatric wards. Symptomatic infection with Salmonella heidelberg developed in 55 children after their admission to the pediatric wards of two adjacent hospiatls in San Juan, Puerto Rico. Many of these children had been hospitalized for the treatment of diarrhea of unidentified etiology. In 25 of these patients, Salmonella bacteremia was documented. Five had clinically unsuspected and untreated bacteremia with no evidence of complications during the follow-up period of four and a half months. The remaining 30 had \"standard\" symptomatic infection due to S. heidelberg. Eight children died; four of these proved to be bacteremic. The index patient, who also introduced the infection into one of the hospitals, was identified. Person to person spread perpetuated the outbreak within and between the two hospitals for nearly four months. Although neonates with salmonellosis had a higher rate of bacteremia than other children, no other specific predisposing factors for Salmonella bacteremia were identified. Laboratory studies of the epidemic strain revealed neither invasive nor enterotoxic properties of the organisms, nor enhanced virulence in laboratory mice. Cohort nursing and isolation of patients with positive cultures halted the epidemic. Nontyphoid Salmonella bacteremia, sometimes clinically unsuspected and self-limited, should be recognized as a frequent accompaniment of Salmonella enteritis in young hospitalized children."} {"id": "PMID:1274985", "title": "Further observations on tuberculin reactions in active tuberculosis.", "content": "One hundred patients with active tuberculosis were tested for tuberculin reactivity within 24 hours of their admission to the hospital. Commercial intermediate tuberculin, Tween stabilized intermediate tuberculin and the Tine test as well as a mumps antigen were applied simultaneously. False negative reactions were obtained in 28 per cent with Tine testing and in 21 per cent with Tween stabilized as well as plain tuberculin. These nonreactors were clinically identifiable as seriously ill with manifestations primarily attributable to protein depletion as a result of their illness. This is not specifically related to the effects of tuberculosis itself, but can be demonstrated in patients suffering the same sequelae of other debilitating illness. After two weeks of protein supplementation via a high calorie, high protein, hospital diet, skin reactivity was restored in the vast majority of these nonreactors. It is concluded that the lack of tuberculin reactivity on hospital admission probably results from impaired lymphocyte function in patients suffering serious protein depletion as a result of their illness; it is not attributable to deficiencies in the tuberculin test itself.", "contents": "Further observations on tuberculin reactions in active tuberculosis. One hundred patients with active tuberculosis were tested for tuberculin reactivity within 24 hours of their admission to the hospital. Commercial intermediate tuberculin, Tween stabilized intermediate tuberculin and the Tine test as well as a mumps antigen were applied simultaneously. False negative reactions were obtained in 28 per cent with Tine testing and in 21 per cent with Tween stabilized as well as plain tuberculin. These nonreactors were clinically identifiable as seriously ill with manifestations primarily attributable to protein depletion as a result of their illness. This is not specifically related to the effects of tuberculosis itself, but can be demonstrated in patients suffering the same sequelae of other debilitating illness. After two weeks of protein supplementation via a high calorie, high protein, hospital diet, skin reactivity was restored in the vast majority of these nonreactors. It is concluded that the lack of tuberculin reactivity on hospital admission probably results from impaired lymphocyte function in patients suffering serious protein depletion as a result of their illness; it is not attributable to deficiencies in the tuberculin test itself."} {"id": "PMID:1274986", "title": "Clinical usefulness of 67gallium scanning in the malignant lymphomas.", "content": "To determine the clinical usefulness of 67 gallium (Ga) scanning in the evaluation of patients with lymphomas, we reviewed 142 total body Ga scans performed on 44 patients with Hodgkin's disease and 53 patients with non-Hodgkin's lymphoma. Fifty-two per cent (123 of 236) of known disease sites were detected on scan. The false-positive rate was less than 5 per cent. The accuracy of detecting lymphoma varied in individual anatomic areas from 33 per cent in the axilla to 73 per cent in the thorax. In eight patients with bone involvement, all bone lesions were detected on scan. The size of the lesion appeared to influence accuracy, since tumors greater than 3 cm in diameter were more often positive.", "contents": "Clinical usefulness of 67gallium scanning in the malignant lymphomas. To determine the clinical usefulness of 67 gallium (Ga) scanning in the evaluation of patients with lymphomas, we reviewed 142 total body Ga scans performed on 44 patients with Hodgkin's disease and 53 patients with non-Hodgkin's lymphoma. Fifty-two per cent (123 of 236) of known disease sites were detected on scan. The false-positive rate was less than 5 per cent. The accuracy of detecting lymphoma varied in individual anatomic areas from 33 per cent in the axilla to 73 per cent in the thorax. In eight patients with bone involvement, all bone lesions were detected on scan. The size of the lesion appeared to influence accuracy, since tumors greater than 3 cm in diameter were more often positive."} {"id": "PMID:1274988", "title": "Multifocal eosinophilic granuloma (\"Hand-Schuller-Christian disease\"). Report illustrating H-S-C chronicity and diagnostic challenge.", "content": "We have described an unusual case of multifocal eosinophilic granuloma (\"Hand-Schueller-Christian disease\") in a middle-aged woman. The case underscores the varied and subtle nature of the disease presentation and the extent to which many organ systems may become involved. Unusual features of her case include atypical bone roentgenograms, cutaneous anergy, panhypopituitarism and evidence of diffuse central nervous system dysfunction. Several features of multifocal eosinophilic granuloma present in the older age group are different from those presenting in children and young adults. Finally, multifocal eosinophilic granuloma may present all the clinical and laboratory features of a progressive, chronic disease.", "contents": "Multifocal eosinophilic granuloma (\"Hand-Schuller-Christian disease\"). Report illustrating H-S-C chronicity and diagnostic challenge. We have described an unusual case of multifocal eosinophilic granuloma (\"Hand-Schueller-Christian disease\") in a middle-aged woman. The case underscores the varied and subtle nature of the disease presentation and the extent to which many organ systems may become involved. Unusual features of her case include atypical bone roentgenograms, cutaneous anergy, panhypopituitarism and evidence of diffuse central nervous system dysfunction. Several features of multifocal eosinophilic granuloma present in the older age group are different from those presenting in children and young adults. Finally, multifocal eosinophilic granuloma may present all the clinical and laboratory features of a progressive, chronic disease."} {"id": "PMID:1274989", "title": "Cogan's syndrome: a systemic vasculitis.", "content": "Nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction (Cogan's syndrome) is a rare clinical entity. We have reviewed 53 cases (including one of our own) of this disease. In 72 per cent of the affected patients there was an underlying systemic process, often a vasculitis. Ten per cent had fatal or near fatal aortic valvular disease, which has been shown to be amenable to surgical intervention. Other systemic manifestations have included congestive heart failure, gastrointestinal hemorrhage, adenopathy, splenomegaly, hypertension, musculoskeletal involvement and eosinophilia. The clinical course is extremely variable, ranging from months to over 15 years with a minimal five year survival of 28 per cent. Medical therapy with corticosteroids has been beneficial but has only limited effect on symptoms of vestibuloauditory dysfunction. Cogan's syndrome appears to be a manifestation of a systemic disorder which is often apparent only after long-term follow-up.", "contents": "Cogan's syndrome: a systemic vasculitis. Nonsyphilitic interstitial keratitis with vestibuloauditory dysfunction (Cogan's syndrome) is a rare clinical entity. We have reviewed 53 cases (including one of our own) of this disease. In 72 per cent of the affected patients there was an underlying systemic process, often a vasculitis. Ten per cent had fatal or near fatal aortic valvular disease, which has been shown to be amenable to surgical intervention. Other systemic manifestations have included congestive heart failure, gastrointestinal hemorrhage, adenopathy, splenomegaly, hypertension, musculoskeletal involvement and eosinophilia. The clinical course is extremely variable, ranging from months to over 15 years with a minimal five year survival of 28 per cent. Medical therapy with corticosteroids has been beneficial but has only limited effect on symptoms of vestibuloauditory dysfunction. Cogan's syndrome appears to be a manifestation of a systemic disorder which is often apparent only after long-term follow-up."} {"id": "PMID:1274990", "title": "Bronchoconstriction and pulmonary hypertension during abortion induced by 15-methyl-prostaglandin F2alpha.", "content": "Patients have experienced severe breathlessness during second trimester abortion initiated by the intramuscular injection of 15-methyl-prostaglandin F2alpha (15-me-PGF2alpha). In four healthy women given 400 mug of 15-me-PGF2alpha to induce abortion, pulmonary function tests showed reductions in arterial oxygen tension, maximum expired air flow and vital capacity. Residual lung volume and the slope of phase III of the closing volume curves increased.", "contents": "Bronchoconstriction and pulmonary hypertension during abortion induced by 15-methyl-prostaglandin F2alpha. Patients have experienced severe breathlessness during second trimester abortion initiated by the intramuscular injection of 15-methyl-prostaglandin F2alpha (15-me-PGF2alpha). In four healthy women given 400 mug of 15-me-PGF2alpha to induce abortion, pulmonary function tests showed reductions in arterial oxygen tension, maximum expired air flow and vital capacity. Residual lung volume and the slope of phase III of the closing volume curves increased."} {"id": "PMID:1274991", "title": "Chronic thromboembolic occlusion of main pulmonary artery or primary branches. Case report and review of the literature.", "content": "Chronic thromboembolic occlusion of the left pulmonary artery in a 36 year old woman is described, and similar cases reported in the past 15 years are discussed. On review, this disease remains a rare entity. In the majority of cases, the etiology is thrombophlebitis and acute pulmonary embolism. Associated cardiopulmonary disease is uncommon. The most common presenting symptom is unexplained dyspnea, and the majority of patients have past histories of hemoptysis. Acute cardiovascular collapse is distinctly rare. Most physical signs and laboratory tests are normal or nonspecific. The perfusion lung scan, although nonspecific, is the best screening test. Antemortem diagnosis, with rare exception, is established by pulmonary angiography. Eleven patients have been operated on: thromboembolectomy in nine, saphenous vein graft in one and pneumonectomy in one. Operative mortality was 36 per cent (four of 11), definite improvement was seen in 46 per cent (five of 11), and 18 per cent (two of 11) survived the operation with no improvement. The role of medical therapy in this disease is considered.", "contents": "Chronic thromboembolic occlusion of main pulmonary artery or primary branches. Case report and review of the literature. Chronic thromboembolic occlusion of the left pulmonary artery in a 36 year old woman is described, and similar cases reported in the past 15 years are discussed. On review, this disease remains a rare entity. In the majority of cases, the etiology is thrombophlebitis and acute pulmonary embolism. Associated cardiopulmonary disease is uncommon. The most common presenting symptom is unexplained dyspnea, and the majority of patients have past histories of hemoptysis. Acute cardiovascular collapse is distinctly rare. Most physical signs and laboratory tests are normal or nonspecific. The perfusion lung scan, although nonspecific, is the best screening test. Antemortem diagnosis, with rare exception, is established by pulmonary angiography. Eleven patients have been operated on: thromboembolectomy in nine, saphenous vein graft in one and pneumonectomy in one. Operative mortality was 36 per cent (four of 11), definite improvement was seen in 46 per cent (five of 11), and 18 per cent (two of 11) survived the operation with no improvement. The role of medical therapy in this disease is considered."} {"id": "PMID:1274992", "title": "Endocarditis due to accidental penetrating foreign bodies.", "content": "A 15 year old boy had an eight month history of recurrent fever, malaise and poor appetite. Chest roentgenogram revealed a foreign object overlying the right ventricle. Multiple blood cultures grew Enterobacter cloacae. The patients condition improved and blood cultures became negative following gentamicin and carbenicillin therapy. E. cloacae was isolated from the foreign body (a finishing nail) at surgery. Antimicrobial therapy was continued for a total of 30 days, and the patient made an uneventful recovery.", "contents": "Endocarditis due to accidental penetrating foreign bodies. A 15 year old boy had an eight month history of recurrent fever, malaise and poor appetite. Chest roentgenogram revealed a foreign object overlying the right ventricle. Multiple blood cultures grew Enterobacter cloacae. The patients condition improved and blood cultures became negative following gentamicin and carbenicillin therapy. E. cloacae was isolated from the foreign body (a finishing nail) at surgery. Antimicrobial therapy was continued for a total of 30 days, and the patient made an uneventful recovery."} {"id": "PMID:1274993", "title": "Arizona hinshawii osteomyelitis with antecedent enteric fever and sepsis. A case report with a review of the literature.", "content": "A case of Arizona osteomyelitis of the spine which occurred 11 months after an episode of gastroenteritis and enteric fever is presented. As close biochemical and antigenic relative of Salmonella, Arizona infection produces a similar clinical course with gastrointestinal manifestations frequently preceding localized infections by several months. The boney lesion in the present case and in three of the four other cases of Arizona osteomyelitis described in the literature was a chronic inflammation which may have a xanthomatous component. The bone destruction caused by Arizona infection is less severe than that of tuberculosis or pyogenic osteomyelitis. Proposed treatment of Arizona osteomyelitis consists of debridement of the localized infection and long term antimicrobial therapy.", "contents": "Arizona hinshawii osteomyelitis with antecedent enteric fever and sepsis. A case report with a review of the literature. A case of Arizona osteomyelitis of the spine which occurred 11 months after an episode of gastroenteritis and enteric fever is presented. As close biochemical and antigenic relative of Salmonella, Arizona infection produces a similar clinical course with gastrointestinal manifestations frequently preceding localized infections by several months. The boney lesion in the present case and in three of the four other cases of Arizona osteomyelitis described in the literature was a chronic inflammation which may have a xanthomatous component. The bone destruction caused by Arizona infection is less severe than that of tuberculosis or pyogenic osteomyelitis. Proposed treatment of Arizona osteomyelitis consists of debridement of the localized infection and long term antimicrobial therapy."} {"id": "PMID:1274994", "title": "Carpal tunnel syndrome as the initial manifestation of tuberculosis.", "content": "Two patients presenting with carpal tunnel syndrome as the initial manifestations of tuberculosis were seen during a recent four month period at a larg city-county hospital. Although the clinical picture of the carpal tunnel syndrome was typical, a definite diagnosis could not be made until the time of surgery because of the many other causes of the carpal tunnel syndrome. A review of the experience with musculoskeletal tuberculosis and carpal tunnel syndrome at our hospital indicates that although this combination is not common, it is one of the treatable causes of the carpal tunnel syndrome. A review of the literature substantiates this impression.", "contents": "Carpal tunnel syndrome as the initial manifestation of tuberculosis. Two patients presenting with carpal tunnel syndrome as the initial manifestations of tuberculosis were seen during a recent four month period at a larg city-county hospital. Although the clinical picture of the carpal tunnel syndrome was typical, a definite diagnosis could not be made until the time of surgery because of the many other causes of the carpal tunnel syndrome. A review of the experience with musculoskeletal tuberculosis and carpal tunnel syndrome at our hospital indicates that although this combination is not common, it is one of the treatable causes of the carpal tunnel syndrome. A review of the literature substantiates this impression."} {"id": "PMID:1274995", "title": "Candida arthritis. A manifestation of disseminated candidiasis.", "content": "Fungal infections infrequently involve the joints. Review of the literature reveals that Candida arthritis is rare, that it is usually a complication of disseminated candidiasis and that it occurs as a primary joint infection without spread from adjacent osteomyelitis. In the patient we describe Candida arthritis and bursitis of separate joints developed as a late manifestation of disseminated infection following \"transient\" C. tropicalis fungemia. Treatment consisting of aspiration and parenteral amphotericin B eradicated the joint infection without the need for surgery. Bursectomy, however, was required to eradicate the bursal infection. Awareness of this as well as other late complications of candidemia which signify disseminated infection is important. Optimal therapy will be determined only by further clinical experience with this unusual manifestation of Candida infection.", "contents": "Candida arthritis. A manifestation of disseminated candidiasis. Fungal infections infrequently involve the joints. Review of the literature reveals that Candida arthritis is rare, that it is usually a complication of disseminated candidiasis and that it occurs as a primary joint infection without spread from adjacent osteomyelitis. In the patient we describe Candida arthritis and bursitis of separate joints developed as a late manifestation of disseminated infection following \"transient\" C. tropicalis fungemia. Treatment consisting of aspiration and parenteral amphotericin B eradicated the joint infection without the need for surgery. Bursectomy, however, was required to eradicate the bursal infection. Awareness of this as well as other late complications of candidemia which signify disseminated infection is important. Optimal therapy will be determined only by further clinical experience with this unusual manifestation of Candida infection."} {"id": "PMID:1274996", "title": "Job analysis in the clinical laboratory.", "content": "Questionnaires were sent to 111 hospitals located within a 100-mile radius of Morgantown, West Virginia. In the 55 responding hospitals, 1,532 laboratory workers were employed; of this total, 399 were MT(ASCP), 55 were MLT(ASCP), 262 were CLA(ASCP), and 816 were not certified by the Board of Registry of the American Society of Clinical Pathologists (ASCP). Participating hospital laboratory directors were asked to distribute task inventories to medical technologists and to individuals not certified as MT(ASCP). One hundred sixty-five task inventories were completed and returned for analysis. Using the chi square test, comparison was made between the tasks performed by ASCP-certified medical technologists and ASCP-certified laboratory assistants. Both performed essentially the same tasks in the clinical laboratories included in this study. In the final analysis, teaching and supervision were performed more frequently by MTs than by CLAs.", "contents": "Job analysis in the clinical laboratory. Questionnaires were sent to 111 hospitals located within a 100-mile radius of Morgantown, West Virginia. In the 55 responding hospitals, 1,532 laboratory workers were employed; of this total, 399 were MT(ASCP), 55 were MLT(ASCP), 262 were CLA(ASCP), and 816 were not certified by the Board of Registry of the American Society of Clinical Pathologists (ASCP). Participating hospital laboratory directors were asked to distribute task inventories to medical technologists and to individuals not certified as MT(ASCP). One hundred sixty-five task inventories were completed and returned for analysis. Using the chi square test, comparison was made between the tasks performed by ASCP-certified medical technologists and ASCP-certified laboratory assistants. Both performed essentially the same tasks in the clinical laboratories included in this study. In the final analysis, teaching and supervision were performed more frequently by MTs than by CLAs."} {"id": "PMID:1274997", "title": "The cloak of competence: years later.", "content": "A sample of the persons in Edgerton's 1960-1961 study, The Cloak of Competence, was revisited in 1972-1973. The life circumstances of many of these persons had improved, but predictions of the direction and nature of community adjustment in a number of cases proved to be inaccurate. We discussed the issue of diversity in these cases and factors which make prediction problematic, such as environmental variables (as opposed to personal ones) and the effects of time on individual adaptation. Caution was suggested in looking at short-term adaptation without considering these factors. The importance of recognizing the individual's own definition of success was also stressed.", "contents": "The cloak of competence: years later. A sample of the persons in Edgerton's 1960-1961 study, The Cloak of Competence, was revisited in 1972-1973. The life circumstances of many of these persons had improved, but predictions of the direction and nature of community adjustment in a number of cases proved to be inaccurate. We discussed the issue of diversity in these cases and factors which make prediction problematic, such as environmental variables (as opposed to personal ones) and the effects of time on individual adaptation. Caution was suggested in looking at short-term adaptation without considering these factors. The importance of recognizing the individual's own definition of success was also stressed."} {"id": "PMID:1274998", "title": "Transfer as a result of synthetic and analytic reading instruction.", "content": "Fifty EMR children and an equal number of nonretarded children were paired on the basis of WISC vocabulary scores. Pairs were then randomly assigned to one of two conditions (synthetic or analytic). Children in the analytic condition learned to read words printed in a contrived alphabet by a whole-word method, and children in the synthetic condition learned the same words by a parts-to-whole method. At the end of each of three learning sessions, children identified transfer words, including some which were consistent with those taught in phoneme-grapheme relationships and some that were inconsistent. The synthetic method promoted identification of both consistent and inconsistent transfer words for both retarded and nonretarded children.", "contents": "Transfer as a result of synthetic and analytic reading instruction. Fifty EMR children and an equal number of nonretarded children were paired on the basis of WISC vocabulary scores. Pairs were then randomly assigned to one of two conditions (synthetic or analytic). Children in the analytic condition learned to read words printed in a contrived alphabet by a whole-word method, and children in the synthetic condition learned the same words by a parts-to-whole method. At the end of each of three learning sessions, children identified transfer words, including some which were consistent with those taught in phoneme-grapheme relationships and some that were inconsistent. The synthetic method promoted identification of both consistent and inconsistent transfer words for both retarded and nonretarded children."} {"id": "PMID:1274999", "title": "Teaching styles of mothers and the match-to-sample performance of their retarded preschool-age- children.", "content": "Twenty-one mothers and their preschool-age retarded children were observed during three structured teaching sessions. Each session was rated for various forms of maternal preresponse and postresponse activity as well as performance of the children. The results indicated that the most frequent forms of maternal behavior were preresponse verbal directions and instructions; however, the best predictor of children's correct performance was postresponse positive feedback. Patterns of intercorrelations among maternal measures were generally consistent with those reported by Hess and Shipman (1965). The hypothesis was advanced that maternal postresponse feedback may occur as the result of correct responding which, in turn, is more directly affected by other aspects of teaching style.", "contents": "Teaching styles of mothers and the match-to-sample performance of their retarded preschool-age- children. Twenty-one mothers and their preschool-age retarded children were observed during three structured teaching sessions. Each session was rated for various forms of maternal preresponse and postresponse activity as well as performance of the children. The results indicated that the most frequent forms of maternal behavior were preresponse verbal directions and instructions; however, the best predictor of children's correct performance was postresponse positive feedback. Patterns of intercorrelations among maternal measures were generally consistent with those reported by Hess and Shipman (1965). The hypothesis was advanced that maternal postresponse feedback may occur as the result of correct responding which, in turn, is more directly affected by other aspects of teaching style."} {"id": "PMID:1275000", "title": "Comparison of two procedures for fostering the development of the object construct.", "content": "To determine the extent to which training can effect acquisition and retention of the object construct, we exposed 21 severely mentally retarded individuals to training or control conditions for about 10 minutes per day on 8 days. There were two training procedures: one that seemed typical of previous efforts to foster the object construct and a second that differed primarily in the size of the steps in the systematic chain of tasks required of the subjects. Both procedures affected acquisition significantly and equally but neither appeared to result in long-term retention.", "contents": "Comparison of two procedures for fostering the development of the object construct. To determine the extent to which training can effect acquisition and retention of the object construct, we exposed 21 severely mentally retarded individuals to training or control conditions for about 10 minutes per day on 8 days. There were two training procedures: one that seemed typical of previous efforts to foster the object construct and a second that differed primarily in the size of the steps in the systematic chain of tasks required of the subjects. Both procedures affected acquisition significantly and equally but neither appeared to result in long-term retention."} {"id": "PMID:1275001", "title": "Acquisition and retention of a mediational strategy for PA learning in EMR children.", "content": "The ability of EMR children to acquire and retain a mediational strategy for PA learning was demonstrated by a training procedure which consisted of the sequencing of consecutive lists under varying degrees of mediational facilitation. The components of the training procedure included training interval, overt verbalization, and verbal context combined with imagery instruction. Forty-five EMR children (mean CA = 11.26; mean IQ = 63.33) were randomly assigned to one of three groups: mediation, standard, and control. Analyses of data showed significantly superior performance of the mediation group in acquisition and retention of the mediational strategy. The pedagogical implications of the study were discussed.", "contents": "Acquisition and retention of a mediational strategy for PA learning in EMR children. The ability of EMR children to acquire and retain a mediational strategy for PA learning was demonstrated by a training procedure which consisted of the sequencing of consecutive lists under varying degrees of mediational facilitation. The components of the training procedure included training interval, overt verbalization, and verbal context combined with imagery instruction. Forty-five EMR children (mean CA = 11.26; mean IQ = 63.33) were randomly assigned to one of three groups: mediation, standard, and control. Analyses of data showed significantly superior performance of the mediation group in acquisition and retention of the mediational strategy. The pedagogical implications of the study were discussed."} {"id": "PMID:1275002", "title": "Interpersonal interactions between institutionalized retarded children and their attendants.", "content": "An observational method was devised to enable detailed analysis of the behavioral and situational components of aide-resident interpersonal interactions in an institutional ward for retarded children. With this device we measured mode of communication, interpersonal affect, response to the initiator of an encounter, the context within which the interaction occurs, and a mand/tact dimension. In this article, the development and validation of the scale, including data on its reliablity, utiliy, and communicability in training novice observers, was reported. Interrater agreement in each dimension exceeded 80 percent, averaging 89 percent over all categories. Observations over a 7-week period indicated that the dormitory was consistently characterized by child-care and ward-management activities and a neutral affective atmosphere in which aides initiated most of the interactions. The observational method appears appropriate for evaluating interventions designed to improve the quality of residential treatment.", "contents": "Interpersonal interactions between institutionalized retarded children and their attendants. An observational method was devised to enable detailed analysis of the behavioral and situational components of aide-resident interpersonal interactions in an institutional ward for retarded children. With this device we measured mode of communication, interpersonal affect, response to the initiator of an encounter, the context within which the interaction occurs, and a mand/tact dimension. In this article, the development and validation of the scale, including data on its reliablity, utiliy, and communicability in training novice observers, was reported. Interrater agreement in each dimension exceeded 80 percent, averaging 89 percent over all categories. Observations over a 7-week period indicated that the dormitory was consistently characterized by child-care and ward-management activities and a neutral affective atmosphere in which aides initiated most of the interactions. The observational method appears appropriate for evaluating interventions designed to improve the quality of residential treatment."} {"id": "PMID:1275003", "title": "Factor structure and correlates of adaptive behavior in noninstitutionalized retarded adults.", "content": "Forty mentally retarded adults working at a vocational training center were rated by their counselors on the 10 behavior domains of the Adaptive Behavior Scale. A factor analysis yielded the following factors: 1, personal independence; 2, personal responsibility; 3, productivity; and 4, social responsibility. A regression analysis of the four factors on the variables of age, sex, verbal IQ, performance IQ, and maternal trust showed that the predictors together accounted for 75 percent of the variance in Factor 1 and very little of the variance in the other factors. Theoretical and practical implications of the results were discussed.", "contents": "Factor structure and correlates of adaptive behavior in noninstitutionalized retarded adults. Forty mentally retarded adults working at a vocational training center were rated by their counselors on the 10 behavior domains of the Adaptive Behavior Scale. A factor analysis yielded the following factors: 1, personal independence; 2, personal responsibility; 3, productivity; and 4, social responsibility. A regression analysis of the four factors on the variables of age, sex, verbal IQ, performance IQ, and maternal trust showed that the predictors together accounted for 75 percent of the variance in Factor 1 and very little of the variance in the other factors. Theoretical and practical implications of the results were discussed."} {"id": "PMID:1275004", "title": "Comparison of three procedures in reducing self-injurious behavior.", "content": "In the present study the effects of withdrawal of food, withdrawal of attention, and the simultaneous withdrawal of food and attention on the rate of self-injurious behavior of three profoundly retarded girls during mealtime were investigated. The two treatments that prevented eating led to a marked reduction of self-injurious behavior. Application of the method allowing continuation of eating (withdrawal of attention) resulted in an increased rate of two subjects' self-injurious behavior and had little effect on the rate of self-injurious behavior of the third. An analysis of the data suggests that contingent interruption of meal consumption can reduce the behavior and that rates of self-injurious behavior vary as a result of reinforcement.", "contents": "Comparison of three procedures in reducing self-injurious behavior. In the present study the effects of withdrawal of food, withdrawal of attention, and the simultaneous withdrawal of food and attention on the rate of self-injurious behavior of three profoundly retarded girls during mealtime were investigated. The two treatments that prevented eating led to a marked reduction of self-injurious behavior. Application of the method allowing continuation of eating (withdrawal of attention) resulted in an increased rate of two subjects' self-injurious behavior and had little effect on the rate of self-injurious behavior of the third. An analysis of the data suggests that contingent interruption of meal consumption can reduce the behavior and that rates of self-injurious behavior vary as a result of reinforcement."} {"id": "PMID:1275005", "title": "Establishing conditional discriminations without direct training: stimulus classes and labels.", "content": "An attempt was made to expand the paradigm published by Spradlin, Cotter, and Baxley (1973). Spradlin et al. conditioned subjects to select a choice stimulus in response to two different sample stimuli and then conditioned them to select a new choice stimulus in response to one sample stimulus. The remaining sample stimulus then controlled the second choice stimulus. In the current investigation, two subjects were taught two classes of four symbols each through visual match-to-sample training. When auditory symbols were conditioned to control some members of these two classes, the reamining members came under auditory control without direct training.", "contents": "Establishing conditional discriminations without direct training: stimulus classes and labels. An attempt was made to expand the paradigm published by Spradlin, Cotter, and Baxley (1973). Spradlin et al. conditioned subjects to select a choice stimulus in response to two different sample stimuli and then conditioned them to select a new choice stimulus in response to one sample stimulus. The remaining sample stimulus then controlled the second choice stimulus. In the current investigation, two subjects were taught two classes of four symbols each through visual match-to-sample training. When auditory symbols were conditioned to control some members of these two classes, the reamining members came under auditory control without direct training."} {"id": "PMID:1275006", "title": "Experimental preadmission program to encourgage home care for severely and profoundly retarded children.", "content": "An experimental treatment program was designed to reduce institutionalization of severely and profoundly retarded children under 6 years of age. Subjects were randomly assigned to experimental and control groups. Results showed that counseling with the mother alone tends to result in increased marital conflict as well as a decision to keep the child at home, particularly for parents who are uncertain about their plans and hopes for the child. Since this conflict could defeat the real purpose of fostering the welfare of the child, family counseling should be used and consensus within the family should be sought. Instructing the mother in child-training procedures tends to reduce the number of instances of objectionable child behavior, as well as to induce a decision to keep the child at home, particularly for parents who are uncertain about their hopes and plans for the child.", "contents": "Experimental preadmission program to encourgage home care for severely and profoundly retarded children. An experimental treatment program was designed to reduce institutionalization of severely and profoundly retarded children under 6 years of age. Subjects were randomly assigned to experimental and control groups. Results showed that counseling with the mother alone tends to result in increased marital conflict as well as a decision to keep the child at home, particularly for parents who are uncertain about their plans and hopes for the child. Since this conflict could defeat the real purpose of fostering the welfare of the child, family counseling should be used and consensus within the family should be sought. Instructing the mother in child-training procedures tends to reduce the number of instances of objectionable child behavior, as well as to induce a decision to keep the child at home, particularly for parents who are uncertain about their hopes and plans for the child."} {"id": "PMID:1275008", "title": "An association between the Dalkon Shield and complicated pregnancies among women hospitalized for intrauterine contraceptive device--related disorders.", "content": "A nationwide mail survey of virtually all physicians likely to be involved with intrauterine contraception resulted in 3,502 unduplicated reports of intrauterine contraceptive device (IUD)--related hospitalizations during the first six months of 1973. Dalkon Shield use was significantly more frequent among women hospitalized for a complicated pregnancy than those hospitalized for a non-pregnancy-related disorder. Although the observed association was not substantially altered by stratifications of the mail survey reports by the patient's age, race, or geographical region, the association did not apply to those women whose IUD's were explicitly reported to be of the nulliparous size. Interviews conducted with a probability sample of physicians who had not responded to the survey confirmed that the association between the Dalkon Shield and complicated pregnancy also existed in their experience. An association between the standard Dalkon Shield and complicated pregnancies might reflect an increased rate of pregnancy with this device, an increased rate of complications occurring after zygotic implantation, or perhaps both. Whatever the explanation, the observed association is sufficiently widespread to require further investigations.", "contents": "An association between the Dalkon Shield and complicated pregnancies among women hospitalized for intrauterine contraceptive device--related disorders. A nationwide mail survey of virtually all physicians likely to be involved with intrauterine contraception resulted in 3,502 unduplicated reports of intrauterine contraceptive device (IUD)--related hospitalizations during the first six months of 1973. Dalkon Shield use was significantly more frequent among women hospitalized for a complicated pregnancy than those hospitalized for a non-pregnancy-related disorder. Although the observed association was not substantially altered by stratifications of the mail survey reports by the patient's age, race, or geographical region, the association did not apply to those women whose IUD's were explicitly reported to be of the nulliparous size. Interviews conducted with a probability sample of physicians who had not responded to the survey confirmed that the association between the Dalkon Shield and complicated pregnancy also existed in their experience. An association between the standard Dalkon Shield and complicated pregnancies might reflect an increased rate of pregnancy with this device, an increased rate of complications occurring after zygotic implantation, or perhaps both. Whatever the explanation, the observed association is sufficiently widespread to require further investigations."} {"id": "PMID:1275009", "title": "Relation of obstetric parameters to the concentrations of four pregnancy-associated plasma proteins at term in normal gestation.", "content": "The relations between normal obstetric parameters and the maternal levels of four pregnancy-associated plasma proteins (PAPP) were studied, with the use of plasma samples taken from 187 normal pregnant women within seven days before delivery. PAPP-A levels were correlated with placental and newborn weights. The levels of this pregnancy protein was higher in primigravid women and in groups with higher diastolic blood pressure than in other groups. Women with extremely high PAPP-A concentrations were likely to have extremely large placental weight was not necessarily associated with a high PAPP-A level. PAPP-C was not correlated with placental or newborn weight. The relationship between PAPP-C and maternal age, as well as maternal weight, was significant by one but not in the other three statistical analyses employed. The pregnancy zone protein was found to be correlated with parity. In primigravid women, this protein additionally showed an inverse correlation with the placental weight. Human chorionic somatomammotropin was significantly related to placental weight and inversely related to maternal weight. Its relationship with newborn weight was best seen in primigravid subjects. Other parameters (systolic blood pressure, one- and five-minute Apgar scores, weeks of gestation, days before delivery, newborn sex, and newborn bilirubin level) were not related to any of these pregnancy proteins.", "contents": "Relation of obstetric parameters to the concentrations of four pregnancy-associated plasma proteins at term in normal gestation. The relations between normal obstetric parameters and the maternal levels of four pregnancy-associated plasma proteins (PAPP) were studied, with the use of plasma samples taken from 187 normal pregnant women within seven days before delivery. PAPP-A levels were correlated with placental and newborn weights. The levels of this pregnancy protein was higher in primigravid women and in groups with higher diastolic blood pressure than in other groups. Women with extremely high PAPP-A concentrations were likely to have extremely large placental weight was not necessarily associated with a high PAPP-A level. PAPP-C was not correlated with placental or newborn weight. The relationship between PAPP-C and maternal age, as well as maternal weight, was significant by one but not in the other three statistical analyses employed. The pregnancy zone protein was found to be correlated with parity. In primigravid women, this protein additionally showed an inverse correlation with the placental weight. Human chorionic somatomammotropin was significantly related to placental weight and inversely related to maternal weight. Its relationship with newborn weight was best seen in primigravid subjects. Other parameters (systolic blood pressure, one- and five-minute Apgar scores, weeks of gestation, days before delivery, newborn sex, and newborn bilirubin level) were not related to any of these pregnancy proteins."} {"id": "PMID:1275010", "title": "A simple assessment of the risk of low birth weight to select women for nutritional intervention.", "content": "There is growing evidence that the high prevalence of low-birth-weight (LBW) babies, a characteristic of many poor societies, can be significantly reduced through nutritional intervention programs. In order to increase the efficiency of these programs, pregnant women at risk of delivering LBW babies must be identified. Several risk scales have been extensively used in urban populations of developed countries. However, these indicators are of little use in poor communities, since most of them require expensive laboratory techniques, a long interview, at least two visits to a health center, and a precise estimation of gestational age. The present paper proposes several risk indicators of LBW, appropriate for use in areas with inadequate health resources. In a four-year longitudinal study of pregnant women from poor rural villages in Guatemala, mothers of LBW babies were found to be typically small in stature and head circumference. In addition, their houses tended to be of relatively poor quality. The proportion of LBW babies found among women at risk, as defined by these indicators, was significantly lower among women with similar characteristics receiving adequate food supplementation during pregnancy. Categories of high risk were based on maternal height, head circumference, and house quality. It is concluded that use of these categories will increase the efficiency of these programs without decreasing significantly their effectiveness.", "contents": "A simple assessment of the risk of low birth weight to select women for nutritional intervention. There is growing evidence that the high prevalence of low-birth-weight (LBW) babies, a characteristic of many poor societies, can be significantly reduced through nutritional intervention programs. In order to increase the efficiency of these programs, pregnant women at risk of delivering LBW babies must be identified. Several risk scales have been extensively used in urban populations of developed countries. However, these indicators are of little use in poor communities, since most of them require expensive laboratory techniques, a long interview, at least two visits to a health center, and a precise estimation of gestational age. The present paper proposes several risk indicators of LBW, appropriate for use in areas with inadequate health resources. In a four-year longitudinal study of pregnant women from poor rural villages in Guatemala, mothers of LBW babies were found to be typically small in stature and head circumference. In addition, their houses tended to be of relatively poor quality. The proportion of LBW babies found among women at risk, as defined by these indicators, was significantly lower among women with similar characteristics receiving adequate food supplementation during pregnancy. Categories of high risk were based on maternal height, head circumference, and house quality. It is concluded that use of these categories will increase the efficiency of these programs without decreasing significantly their effectiveness."} {"id": "PMID:1275011", "title": "Immunobiological function of the syncytiotrophoblast: a new theory.", "content": "The main purpose of this paper is to present our hypothesis concerning the antigen-antibody complex formation and the resolution system inside the syncytiotrophoblast to explain immunologic fetomaternal relationships. This hypothesis, derived from the results of our experiments, might be an answer to why the fetus is not rejected by the mother, in contradistinction to other allografts. We also believe that this hypothesis makes important contributions to the explanation of the immunologic processes of cells, i.e., those processes which work against antigens inside a living body.", "contents": "Immunobiological function of the syncytiotrophoblast: a new theory. The main purpose of this paper is to present our hypothesis concerning the antigen-antibody complex formation and the resolution system inside the syncytiotrophoblast to explain immunologic fetomaternal relationships. This hypothesis, derived from the results of our experiments, might be an answer to why the fetus is not rejected by the mother, in contradistinction to other allografts. We also believe that this hypothesis makes important contributions to the explanation of the immunologic processes of cells, i.e., those processes which work against antigens inside a living body."} {"id": "PMID:1275012", "title": "A rapid, flow-through column radioimmunoassay for human chorionic somatomammotropin.", "content": "A rapid, flow-through, column, nonequilibrium radioimmunoassay for human chorionic somatomammotropin (HCS) is described. The total incubation time is about 1 hour, and no centrifugation is needed. Reproducibility, sensitivity, specificity, recovery, and parallelism are adequate for clinical utility. Hormone levels in a variety of pregnancy sera assayed by this column method are closely related to results from another more conventional radioimmunoassay method.", "contents": "A rapid, flow-through column radioimmunoassay for human chorionic somatomammotropin. A rapid, flow-through, column, nonequilibrium radioimmunoassay for human chorionic somatomammotropin (HCS) is described. The total incubation time is about 1 hour, and no centrifugation is needed. Reproducibility, sensitivity, specificity, recovery, and parallelism are adequate for clinical utility. Hormone levels in a variety of pregnancy sera assayed by this column method are closely related to results from another more conventional radioimmunoassay method."} {"id": "PMID:1275013", "title": "Extraperitoneal cesarean section: a new need for old skills. A preliminary report.", "content": "Preliminary results of the effect of extraperitoneal cesarean section on operative and postoperative morbidity are presented. The extraperitoneal technique did not prolong delivery time or operative time, as compared to transperitoneal cesarean section. Postoperative febrile morbidity seemed to be less in the patients who had extraperitoneal cesarean section, even when compared to randomly selected transperitoneal cases. Further data will be necessary to conclude that renewed interest in this technique is warranted.", "contents": "Extraperitoneal cesarean section: a new need for old skills. A preliminary report. Preliminary results of the effect of extraperitoneal cesarean section on operative and postoperative morbidity are presented. The extraperitoneal technique did not prolong delivery time or operative time, as compared to transperitoneal cesarean section. Postoperative febrile morbidity seemed to be less in the patients who had extraperitoneal cesarean section, even when compared to randomly selected transperitoneal cases. Further data will be necessary to conclude that renewed interest in this technique is warranted."} {"id": "PMID:1275014", "title": "Fetal growth retardation in relation to maternal smoking and weight gain in pregnancy.", "content": "Two types of fetal growth retardation were recognized in term infants. One type was characterized by an abnormally low ponderal index (defined as birth weight in grams X 100 divided by crown-heel length in cubic centimeters.) The other type of growth-retarded infants had abnormally short crown-heel lengths for fetal age. Both types were observed under all conditions studied. However, mothers who smoked cigarettes during pregnancy were more likely to have infants with short body lengths for dates, whereas mothers who had low weight gain in pregnancy were more likely to have infants with low ponderal indices. Social group, prepregnancy weight, parity, marital status, and fetal sex were found to be less determinant of fetal growth than were maternal weight gain and smoking habits.", "contents": "Fetal growth retardation in relation to maternal smoking and weight gain in pregnancy. Two types of fetal growth retardation were recognized in term infants. One type was characterized by an abnormally low ponderal index (defined as birth weight in grams X 100 divided by crown-heel length in cubic centimeters.) The other type of growth-retarded infants had abnormally short crown-heel lengths for fetal age. Both types were observed under all conditions studied. However, mothers who smoked cigarettes during pregnancy were more likely to have infants with short body lengths for dates, whereas mothers who had low weight gain in pregnancy were more likely to have infants with low ponderal indices. Social group, prepregnancy weight, parity, marital status, and fetal sex were found to be less determinant of fetal growth than were maternal weight gain and smoking habits."} {"id": "PMID:1275015", "title": "Fetal scalp abscess secondary to intrauterine monitoring.", "content": "Thirty-one cases of fetal scalp abscess secondary to internal fetal monitoring over a 32 month period were reviewed. The over-all incidence was 1:230 monitored labors, or 0.4 per cent. Twenty-nine infants were cultured, with no growth in 10, Staphylococcus epidermidis in 11, and pathogenic organisms in the remainder. Gram stains of the exudates generally supported the culture results. All cases responded to drainage, local care, and systemic antibiotics, with no deaths. One case of osteomyelitis of the skull was confirmed roentgenographically. A strong correlation between prolonged rupture of the membranes and scalp abscess was observed, but no definite infectious origin was confirmed. The etiology of scalp abscess secondary to monitoring remains obscure.", "contents": "Fetal scalp abscess secondary to intrauterine monitoring. Thirty-one cases of fetal scalp abscess secondary to internal fetal monitoring over a 32 month period were reviewed. The over-all incidence was 1:230 monitored labors, or 0.4 per cent. Twenty-nine infants were cultured, with no growth in 10, Staphylococcus epidermidis in 11, and pathogenic organisms in the remainder. Gram stains of the exudates generally supported the culture results. All cases responded to drainage, local care, and systemic antibiotics, with no deaths. One case of osteomyelitis of the skull was confirmed roentgenographically. A strong correlation between prolonged rupture of the membranes and scalp abscess was observed, but no definite infectious origin was confirmed. The etiology of scalp abscess secondary to monitoring remains obscure."} {"id": "PMID:1275016", "title": "Absolute neonatal insulin levels in children of insulin-requiring diabetic patients.", "content": "This report describes the relationship between cord plasma insulin and neonatal blood glucose in nine children of diabetic patients treated during pregnancy with monocomponent insulins. Plasma insulin in cord blood was similar to that found in patients with gestational diabetes and was not related to either neonatal blood glucose or maternal diabetic control.", "contents": "Absolute neonatal insulin levels in children of insulin-requiring diabetic patients. This report describes the relationship between cord plasma insulin and neonatal blood glucose in nine children of diabetic patients treated during pregnancy with monocomponent insulins. Plasma insulin in cord blood was similar to that found in patients with gestational diabetes and was not related to either neonatal blood glucose or maternal diabetic control."} {"id": "PMID:1275017", "title": "Incidence of infections associated with the intrauterine contraceptive device in an isolated community.", "content": "In an attempt to estimate more precisely the frequency of infections associated with the intrauterine contraceptive device (IUD), all gynecologic morbidity resulting from infection and occurring during a two-year period in an isolated community was reviewed. Ten septic abortions occurred, and all but one were associated with IUD use. In 26 gynecologic inpatients (41 per cent of all admissions for acute pelvic inflammatory disease), pelvic infection was associated with IUD use. In contradistinction to the septic abortion data, implicating only the Dalkon Shield, the gynecologic infections were associated with various types of devices.", "contents": "Incidence of infections associated with the intrauterine contraceptive device in an isolated community. In an attempt to estimate more precisely the frequency of infections associated with the intrauterine contraceptive device (IUD), all gynecologic morbidity resulting from infection and occurring during a two-year period in an isolated community was reviewed. Ten septic abortions occurred, and all but one were associated with IUD use. In 26 gynecologic inpatients (41 per cent of all admissions for acute pelvic inflammatory disease), pelvic infection was associated with IUD use. In contradistinction to the septic abortion data, implicating only the Dalkon Shield, the gynecologic infections were associated with various types of devices."} {"id": "PMID:1275018", "title": "Microinvasive carcinoma of the cervix.", "content": "The depth and pattern of invasion were compared in 115 cases of microinvasive carcinoma. The 71 invading 1 mm. or less were focal (96 per cent) rather than confluent (4 per cent) and were cured by simple hysterectomy(one vaginal vault recurrence). The 44 invading 2 to 5 mm. showed a confluent pattern in 39 per cent; a need for treating pelvic lymphatics was demonstrated by one with a positive hypogastric lymph node and by two pelvic recurrences. An additional 26 cases assessed as beyond microinvasive (6 to 10 mm. in depth) included five of 16 without radical treatment who died from cancer, while all treated radically survived, including five with lymphatic involvement.", "contents": "Microinvasive carcinoma of the cervix. The depth and pattern of invasion were compared in 115 cases of microinvasive carcinoma. The 71 invading 1 mm. or less were focal (96 per cent) rather than confluent (4 per cent) and were cured by simple hysterectomy(one vaginal vault recurrence). The 44 invading 2 to 5 mm. showed a confluent pattern in 39 per cent; a need for treating pelvic lymphatics was demonstrated by one with a positive hypogastric lymph node and by two pelvic recurrences. An additional 26 cases assessed as beyond microinvasive (6 to 10 mm. in depth) included five of 16 without radical treatment who died from cancer, while all treated radically survived, including five with lymphatic involvement."} {"id": "PMID:1275019", "title": "Scalene node biopsy in the pretreatment staging of carcinoma of the cervix uteri.", "content": "This study reports the experience at the Ellis Fischel State Cancer Hospital with the use of scalene node biopsy for the pretreatment evaluation of patients with carcinoma of the cervix uter. The study was stimulated by a report from the National Cancer Institutes which stated that impalpable scalene nodes contained metastatic cancer in 13 per cent of a series of 84 cases. By a meticulous biopsy technique, we were unable to confirm this high incidence, In a series of 73 cases, no impalpable lymph nodes were found to contain metastatic cancer regardless of the clinical stage of the cancer. Consequently, we have terminated the use of scalene lymph node biopsies in the staging of cervical cancer for primary treatment. The study is still in progress to evaluate patients with recurrent cervical cancer who may possibly require pelvic exenteration. Also, the procedure will be continued in patients referred for further treatment in whom carcinoma was first diagnosed as an unsuspected finding in a hysterectomy specimen.", "contents": "Scalene node biopsy in the pretreatment staging of carcinoma of the cervix uteri. This study reports the experience at the Ellis Fischel State Cancer Hospital with the use of scalene node biopsy for the pretreatment evaluation of patients with carcinoma of the cervix uter. The study was stimulated by a report from the National Cancer Institutes which stated that impalpable scalene nodes contained metastatic cancer in 13 per cent of a series of 84 cases. By a meticulous biopsy technique, we were unable to confirm this high incidence, In a series of 73 cases, no impalpable lymph nodes were found to contain metastatic cancer regardless of the clinical stage of the cancer. Consequently, we have terminated the use of scalene lymph node biopsies in the staging of cervical cancer for primary treatment. The study is still in progress to evaluate patients with recurrent cervical cancer who may possibly require pelvic exenteration. Also, the procedure will be continued in patients referred for further treatment in whom carcinoma was first diagnosed as an unsuspected finding in a hysterectomy specimen."} {"id": "PMID:1275020", "title": "Endometrial aspiration in fertility control. A report of 500 cases.", "content": "Outpatient endometrial aspiration was offered to patients who suspected that they were pregnant, but were within 5 to 21 days after failure of expected menstruation and had a uterus of normal size on pelvic examination. This is a report of 500 consecutive cases treated between September, 1973, and April, 1975. Histologic examination of the aspirated tissue was obtained on all 500 cases (100 per cent). Follow-up examination and urine pregnancy was obtained on 407 patients (81.4 per cent). Histologic evidence of pregnancy was obtained in 323 patients (64.6 per cent). Complications were limited to five infections (1 per cent), only one of which led to hospitalization of the patient, and failure to completely evacuate the pregnant uterus in 39 patients (12.1 per cetn of the 323 pregnant). Thirty-four of these had the uterus emptied by a second outpatient procedure and five patients were hospitalized to complete their abortion.", "contents": "Endometrial aspiration in fertility control. A report of 500 cases. Outpatient endometrial aspiration was offered to patients who suspected that they were pregnant, but were within 5 to 21 days after failure of expected menstruation and had a uterus of normal size on pelvic examination. This is a report of 500 consecutive cases treated between September, 1973, and April, 1975. Histologic examination of the aspirated tissue was obtained on all 500 cases (100 per cent). Follow-up examination and urine pregnancy was obtained on 407 patients (81.4 per cent). Histologic evidence of pregnancy was obtained in 323 patients (64.6 per cent). Complications were limited to five infections (1 per cent), only one of which led to hospitalization of the patient, and failure to completely evacuate the pregnant uterus in 39 patients (12.1 per cetn of the 323 pregnant). Thirty-four of these had the uterus emptied by a second outpatient procedure and five patients were hospitalized to complete their abortion."} {"id": "PMID:1275022", "title": "Clinical significance of fetal heart rate patterns during labor. I. Baseline patterns.", "content": "From a population of 2,774 high-risk patients monitored during labor, 1,304 single pregnancies in cephalic presentation and with direct monitoring for at least 1 hour before completion or cesarean-section were studied. The maternal and fetal clinical data and the tracings were hand reviewed, coded, and programmed for computer analysis. In the record were studied baseline, its changes (tachycardia, fixed, saltatory), the accelerations, and the decelerations (early, variable, late). Fifty-four per cent had some type of FHR deceleration. Accelerations were recorded in over 12 per cent of all cases and were associated with cord problems in 41 per cent. Subgrouping the patients by age of gestation (less than or equal to 36 weeks, 37 to 41 weeks, and greater than or equal to 42 weeks) revealed a 10 per cent prolonged gestation rate and only 6.8 per cent premature; these had a lower 5 minute Apgar score. Fetal weight and age were positively correlated with Apgar score. Baseline changes were much frequent among pre- and postmature infants, particularly tachycardia in the latter (40 per cent). The premature infants had a 25 per cent incidence of fetal distress and the postmature infants had 20 per cent. Neonatal morbidity and mortality rates were very high among premature infants and a mortality rate of 2.3 per cent was found among postmature infants. Saltatory pattern and particularly fixed baseline seem characteristic of prolonged gestation and placental insufficiency. With tachycardia, they constitute subtle symptoms of fetal distress.", "contents": "Clinical significance of fetal heart rate patterns during labor. I. Baseline patterns. From a population of 2,774 high-risk patients monitored during labor, 1,304 single pregnancies in cephalic presentation and with direct monitoring for at least 1 hour before completion or cesarean-section were studied. The maternal and fetal clinical data and the tracings were hand reviewed, coded, and programmed for computer analysis. In the record were studied baseline, its changes (tachycardia, fixed, saltatory), the accelerations, and the decelerations (early, variable, late). Fifty-four per cent had some type of FHR deceleration. Accelerations were recorded in over 12 per cent of all cases and were associated with cord problems in 41 per cent. Subgrouping the patients by age of gestation (less than or equal to 36 weeks, 37 to 41 weeks, and greater than or equal to 42 weeks) revealed a 10 per cent prolonged gestation rate and only 6.8 per cent premature; these had a lower 5 minute Apgar score. Fetal weight and age were positively correlated with Apgar score. Baseline changes were much frequent among pre- and postmature infants, particularly tachycardia in the latter (40 per cent). The premature infants had a 25 per cent incidence of fetal distress and the postmature infants had 20 per cent. Neonatal morbidity and mortality rates were very high among premature infants and a mortality rate of 2.3 per cent was found among postmature infants. Saltatory pattern and particularly fixed baseline seem characteristic of prolonged gestation and placental insufficiency. With tachycardia, they constitute subtle symptoms of fetal distress."} {"id": "PMID:1275023", "title": "Induction of labor with oral prostaglandin E2.", "content": "Prostaglandin E (PGE2) was administered orally for induction of labor to 100 patients. Active labor and progression occurred in 92 per cent of these cases. The dosage regimen used was 0.5 to 1.5 mg. hourly. Amniotomy was performed in most cases once active labor and progression were noted. There were 83 vaginal deliveries and 12 cesarean sections. There were eight failure of induction, one patient left the study, and one was not delivered at that admission. Fetal distress occurred in 10 patients but this was related to cord and placental problems and not to PGE2 per se. Side effects were minimal, the most prominent being nausea and vomiting. Total labor in hours compares to normal labor. Over-all, labor in primigravidas averaged 10.15 hours and 6.5 hours in multiparas. There was a direct relationship of the Bishop score to the start of active labor and progression. PGE2 appears safe and efficacious for inductions of labor at terms.", "contents": "Induction of labor with oral prostaglandin E2. Prostaglandin E (PGE2) was administered orally for induction of labor to 100 patients. Active labor and progression occurred in 92 per cent of these cases. The dosage regimen used was 0.5 to 1.5 mg. hourly. Amniotomy was performed in most cases once active labor and progression were noted. There were 83 vaginal deliveries and 12 cesarean sections. There were eight failure of induction, one patient left the study, and one was not delivered at that admission. Fetal distress occurred in 10 patients but this was related to cord and placental problems and not to PGE2 per se. Side effects were minimal, the most prominent being nausea and vomiting. Total labor in hours compares to normal labor. Over-all, labor in primigravidas averaged 10.15 hours and 6.5 hours in multiparas. There was a direct relationship of the Bishop score to the start of active labor and progression. PGE2 appears safe and efficacious for inductions of labor at terms."} {"id": "PMID:1275024", "title": "Carcinoma of the cervix in oral contraceptive steroid and IUD users and nonusers.", "content": "A total of 40,211 cytologic examinations and subsequent diagnostic procedures resulted in the diagnosis of carcinoma of the cervix in 76 patients. The 76 patients did not demonstrate any variations in use of oral contraceptive steroids or intrauterine devices when compared to 780 randomly selected control patients. This study is in agreement with our earlier report demonstrating no increased risk of carcinoma of the cervix in oral contraceptive steroid users compared to nonusers.", "contents": "Carcinoma of the cervix in oral contraceptive steroid and IUD users and nonusers. A total of 40,211 cytologic examinations and subsequent diagnostic procedures resulted in the diagnosis of carcinoma of the cervix in 76 patients. The 76 patients did not demonstrate any variations in use of oral contraceptive steroids or intrauterine devices when compared to 780 randomly selected control patients. This study is in agreement with our earlier report demonstrating no increased risk of carcinoma of the cervix in oral contraceptive steroid users compared to nonusers."} {"id": "PMID:1275025", "title": "The Pereyra procedure. Favorable experience with 200 operations.", "content": "This communication documents experience with 200 Pereyra operations performed for stress urinary incontinence over a 9 year period. The majority of patients were 35 to 55 years of age, were obese, and had varying degrees of uterovaginal prolapse. More than one fourth also had excessive bleeding and all were best managed by vaginal surgery. Important points in surgical technique are emphasized. Of 188 patients followed, 82 per cent had complete symptomatic relief and another 10.5 per cent were improved. There was a 7.5 per cent failure rate and morbidity was minimal. We conclude that the Pereyra procedure should be considered for stress urinary incontinence whenever vaginal surgery is indicated.", "contents": "The Pereyra procedure. Favorable experience with 200 operations. This communication documents experience with 200 Pereyra operations performed for stress urinary incontinence over a 9 year period. The majority of patients were 35 to 55 years of age, were obese, and had varying degrees of uterovaginal prolapse. More than one fourth also had excessive bleeding and all were best managed by vaginal surgery. Important points in surgical technique are emphasized. Of 188 patients followed, 82 per cent had complete symptomatic relief and another 10.5 per cent were improved. There was a 7.5 per cent failure rate and morbidity was minimal. We conclude that the Pereyra procedure should be considered for stress urinary incontinence whenever vaginal surgery is indicated."} {"id": "PMID:1275026", "title": "Doctors and patients in obstetrics and gynecology: the next 15 years.", "content": "The major impact on the development of obstetrics-gynecology during the next 15 years will come from the substantially increased number of of practicing physicians in the specialty and less rapidly increasing patient population they will serve. Even at present record low fertility rates, the annual number of births in the United States will increase slowly to a level near 4 million by the early 1980's; children already born will contribute to a 16 per cent increase in the female population 15 to 44 years of age between now and 1990. Over the same time interval, the number of practicing specialists will increase dramatically, based on rising numbers of medical school graduates and more Ob-Gyn residents; there will be a 52 per cent increase in certified specialists per unit population over the next 15 years.", "contents": "Doctors and patients in obstetrics and gynecology: the next 15 years. The major impact on the development of obstetrics-gynecology during the next 15 years will come from the substantially increased number of of practicing physicians in the specialty and less rapidly increasing patient population they will serve. Even at present record low fertility rates, the annual number of births in the United States will increase slowly to a level near 4 million by the early 1980's; children already born will contribute to a 16 per cent increase in the female population 15 to 44 years of age between now and 1990. Over the same time interval, the number of practicing specialists will increase dramatically, based on rising numbers of medical school graduates and more Ob-Gyn residents; there will be a 52 per cent increase in certified specialists per unit population over the next 15 years."} {"id": "PMID:1275027", "title": "The cytologic diagnosis of endometrial adenocarcinoma.", "content": "An outpatient diagnositc technique comparable to the Papanicolaou smear for carcinoma of the cervix is needed to permit early recognition of adenocarcinoma of the endometrium. Five different techniques of sampling the endometrial cavity were carried out on 1, 742 patients at the University of Michigan Medical Center. A total of 2,553 specimens were correlated with operating room curettings to assess the accuracy of each sampling technique. The methods of saline irrigation with an antrum cannula, endometrial brush sampling, high-vacuum aspiration, and the Gravlee jet washer proved not to be accurate enough to be used as a routine screeening test. There was excellent correlation (96 per cent) between endometrial biopsies and curettings. In our experience, endometrial biopsy with a suction or basket curette was the diagnostic technique short of curettage which permitted accurate diagnosis.", "contents": "The cytologic diagnosis of endometrial adenocarcinoma. An outpatient diagnositc technique comparable to the Papanicolaou smear for carcinoma of the cervix is needed to permit early recognition of adenocarcinoma of the endometrium. Five different techniques of sampling the endometrial cavity were carried out on 1, 742 patients at the University of Michigan Medical Center. A total of 2,553 specimens were correlated with operating room curettings to assess the accuracy of each sampling technique. The methods of saline irrigation with an antrum cannula, endometrial brush sampling, high-vacuum aspiration, and the Gravlee jet washer proved not to be accurate enough to be used as a routine screeening test. There was excellent correlation (96 per cent) between endometrial biopsies and curettings. In our experience, endometrial biopsy with a suction or basket curette was the diagnostic technique short of curettage which permitted accurate diagnosis."} {"id": "PMID:1275028", "title": "Maternal deaths due to spontaneous subarachnoid hemorrhage.", "content": "Spontaneous subarachnoid hemorrhage due to ruptured berry aneurysm and arteriovenous malformation accounted for 4.4 per cent of all maternal deaths in the State of Minnesota from 1950 to 1973. This catastrophic entiity ranked eighth in frequency regarding all causes of death and third among the nonobstetric causes. An analysis of the 37 deaths among 1,763,824 live births is presented. These 37 patients had delivered 96 infants and had 10 spontaneous abortions prior to current pregnancy. This suggest that pregnancy per se has no appreciable effect upon the occurrence of the hemorrhage. Five of these died in association with labor and delivery, or during a 1 day period-three during labor, one during vaginal delivery, and one only 1 hour postpartum. This is equivalent to 35 per week. On the other hand, 15 occurred during pregnancy (underlivered) (0.4 per week) and 17 during the first 3 months post partum (1.4 per week). These data seem to indicate that labor and delivery increase the risk of spontaneous subarachnoid hemorrhage. The neurologic state of these 37 patients was bad from the very onset of the hemorrhage. Rapid irreversible coma occurred in 34 (76 per cent). Of these 34, 24 (74 per cent) were dead within the first 24 hours and 32 (94 per cent) were dead within the first 4 days following the onset of the hemorrhage.", "contents": "Maternal deaths due to spontaneous subarachnoid hemorrhage. Spontaneous subarachnoid hemorrhage due to ruptured berry aneurysm and arteriovenous malformation accounted for 4.4 per cent of all maternal deaths in the State of Minnesota from 1950 to 1973. This catastrophic entiity ranked eighth in frequency regarding all causes of death and third among the nonobstetric causes. An analysis of the 37 deaths among 1,763,824 live births is presented. These 37 patients had delivered 96 infants and had 10 spontaneous abortions prior to current pregnancy. This suggest that pregnancy per se has no appreciable effect upon the occurrence of the hemorrhage. Five of these died in association with labor and delivery, or during a 1 day period-three during labor, one during vaginal delivery, and one only 1 hour postpartum. This is equivalent to 35 per week. On the other hand, 15 occurred during pregnancy (underlivered) (0.4 per week) and 17 during the first 3 months post partum (1.4 per week). These data seem to indicate that labor and delivery increase the risk of spontaneous subarachnoid hemorrhage. The neurologic state of these 37 patients was bad from the very onset of the hemorrhage. Rapid irreversible coma occurred in 34 (76 per cent). Of these 34, 24 (74 per cent) were dead within the first 24 hours and 32 (94 per cent) were dead within the first 4 days following the onset of the hemorrhage."} {"id": "PMID:1275029", "title": "Maternal deaths in California from 1967 to 1971. A demonstration of the need for mortality review.", "content": "An evaluation of maternal mortality statistics in California from 1967-1971 has been performed. There has been a fall in the maternal mortality rate following the institution of a therapeutic abortion act. However, analysis of the data reveals that there was an increase in the deaths due to hemorrhage and sepsis. At this same time the maternal mortality study committee was discontinued. It is strongly felt that the data demonstrate the need for a continuing review of maternal deaths. A proposal is made to redesign the maternal mortality study committee so that it can fully meet the needs of the medical profession and the patient.", "contents": "Maternal deaths in California from 1967 to 1971. A demonstration of the need for mortality review. An evaluation of maternal mortality statistics in California from 1967-1971 has been performed. There has been a fall in the maternal mortality rate following the institution of a therapeutic abortion act. However, analysis of the data reveals that there was an increase in the deaths due to hemorrhage and sepsis. At this same time the maternal mortality study committee was discontinued. It is strongly felt that the data demonstrate the need for a continuing review of maternal deaths. A proposal is made to redesign the maternal mortality study committee so that it can fully meet the needs of the medical profession and the patient."} {"id": "PMID:1275030", "title": "Treatment of ovarian stromal tumors.", "content": "Fifty-one patients with granulosa-cell tumors and nine patients with Sertoli-Leydig-cell tumors have been treated at the M. D. Anderson Hospital. The most important prognostic finding was the stage of the tumor when first seen. Conservative surgery was utilized in young patients with lesions confined to one ovary. More advanced tumors were treated with maximal tumor resection and postoperative treatment with either irradiation or chemotherapy. Postoperative radiation was given when the tumor capsule had ruptured or residual tumor less than 2 cm. in diameter was present after surgery. Single-agent chemotherapy was ineffective in ovarian stromal tumors, but combination chemotherapy was found to be effective in advanced or recurrent stromal tumors. Actinomycin-D, 5-fluorouracil, and cyclophosphamide were effective in granulosa-cell tumors. Vincristine, actinomycin-D, and cyclophosphamide were effective in Sertoli-Leydig--cell tumors.", "contents": "Treatment of ovarian stromal tumors. Fifty-one patients with granulosa-cell tumors and nine patients with Sertoli-Leydig-cell tumors have been treated at the M. D. Anderson Hospital. The most important prognostic finding was the stage of the tumor when first seen. Conservative surgery was utilized in young patients with lesions confined to one ovary. More advanced tumors were treated with maximal tumor resection and postoperative treatment with either irradiation or chemotherapy. Postoperative radiation was given when the tumor capsule had ruptured or residual tumor less than 2 cm. in diameter was present after surgery. Single-agent chemotherapy was ineffective in ovarian stromal tumors, but combination chemotherapy was found to be effective in advanced or recurrent stromal tumors. Actinomycin-D, 5-fluorouracil, and cyclophosphamide were effective in granulosa-cell tumors. Vincristine, actinomycin-D, and cyclophosphamide were effective in Sertoli-Leydig--cell tumors."} {"id": "PMID:1275031", "title": "Endometriosis and anovulation: a coexisting problem in the infertile female.", "content": "Over an 8 year period, 350 cases of endometriosis (77 per cent confirmed histologically) from the Department of Obstetrics and Gynecology, Baylor College of Medicine, were reviewed. Of these cases, 58 (17 per cent) exhibited significant anovulation as measured by a scoring system. Endometriosis and anovulation can coexist contrary to classic concepts of these diseases. Both infertility factors required treatment to achieve pregnancy. A 43 per cent pregnancy rate reflects the dual infertility problem.", "contents": "Endometriosis and anovulation: a coexisting problem in the infertile female. Over an 8 year period, 350 cases of endometriosis (77 per cent confirmed histologically) from the Department of Obstetrics and Gynecology, Baylor College of Medicine, were reviewed. Of these cases, 58 (17 per cent) exhibited significant anovulation as measured by a scoring system. Endometriosis and anovulation can coexist contrary to classic concepts of these diseases. Both infertility factors required treatment to achieve pregnancy. A 43 per cent pregnancy rate reflects the dual infertility problem."} {"id": "PMID:1275032", "title": "Immunologic aspects of pre-eclampsia.", "content": "It has been suggested by a number of investigators that immune reactions of the mother against antigens of her conceptus contribute to the development of pre-eclampsia. Evidence for and against this hypothesis is reviewed and the possible clinical implications are discussed.", "contents": "Immunologic aspects of pre-eclampsia. It has been suggested by a number of investigators that immune reactions of the mother against antigens of her conceptus contribute to the development of pre-eclampsia. Evidence for and against this hypothesis is reviewed and the possible clinical implications are discussed."} {"id": "PMID:1275033", "title": "Pars plana vitrectomy for the management of sever diabetic retinopathy.", "content": "In 100 severely diseased diabetic eyes we performed pars plana vitrectomy. After a median follow-up time of seven months, major visual improvement was achieved in 49% of the eyes. An additional four eyes maintained a preoperatively good visual acuity resulting in an overall success rate of 53%. Eyes with only vitreous hemorrhages did better (71%) than eyes with posterior retinal detachments (31%). We did not observe new tissue proliferation in any of the operated eyes.", "contents": "Pars plana vitrectomy for the management of sever diabetic retinopathy. In 100 severely diseased diabetic eyes we performed pars plana vitrectomy. After a median follow-up time of seven months, major visual improvement was achieved in 49% of the eyes. An additional four eyes maintained a preoperatively good visual acuity resulting in an overall success rate of 53%. Eyes with only vitreous hemorrhages did better (71%) than eyes with posterior retinal detachments (31%). We did not observe new tissue proliferation in any of the operated eyes."} {"id": "PMID:1275034", "title": "Pars plana vitrectomy for removal of intravitreous Cysticercus.", "content": "Pars plana was used for the removal of an intravitreous cysticercus, with minimal postoperative inflammation and an excellent visual result. This approach avoids lens removal and the visualization provided by the operating microscope allows removal of all vitreous humor particles and debris. The aspirated specimens allowed identification of the Taenia solium cysticercus.", "contents": "Pars plana vitrectomy for removal of intravitreous Cysticercus. Pars plana was used for the removal of an intravitreous cysticercus, with minimal postoperative inflammation and an excellent visual result. This approach avoids lens removal and the visualization provided by the operating microscope allows removal of all vitreous humor particles and debris. The aspirated specimens allowed identification of the Taenia solium cysticercus."} {"id": "PMID:1275035", "title": "Occlusive retinal arteriolitis with neovascularization.", "content": "A 34-year-old white woman who had used oral contraceptives for six years showed an occlusive bilateral retinal arteriolitis that resulted in a branch arteriolar occlusion in the right eye and retinal neovascularization. Three years later, we observed active arteriolitis in the left eye with successive occlusion of several branch arterioles. The disease has shown spontaneous remissions and exacerbations. An extensive medical evaluation revealed only old pulmonary granulomatous disease and an elevated sedimentation rate in association with exacerbations of the arteriolitis.", "contents": "Occlusive retinal arteriolitis with neovascularization. A 34-year-old white woman who had used oral contraceptives for six years showed an occlusive bilateral retinal arteriolitis that resulted in a branch arteriolar occlusion in the right eye and retinal neovascularization. Three years later, we observed active arteriolitis in the left eye with successive occlusion of several branch arterioles. The disease has shown spontaneous remissions and exacerbations. An extensive medical evaluation revealed only old pulmonary granulomatous disease and an elevated sedimentation rate in association with exacerbations of the arteriolitis."} {"id": "PMID:1275036", "title": "Idiopathic focal subretinal neovascularization.", "content": "In 20 patients idiopathic focal subretinal neovascularization was characterized by a solitary focus of subretinal neovascularization at or near the fovea, associated with serous or hemorrhagic detachment of the overlying and adjacent sensory retina, or both. Although the lesions resembled the neovascular membrane seen in the presumed ocular histoplasmosis syndrome, none of the other associated characteristic ophthalmoscopic findings, considered essential to make the latter diagnosis, were apparent. In this group of patients, the incidence of positive histoplasmin skin tests was no greater than in the general population. Of the 20 patients, two had bilateral disease. In no case were there any other lesions of any kind in the afflicted or the opposite eye. The disease is self-limited over a variable period of time, but may result in extensive scarring with loss of central vision.", "contents": "Idiopathic focal subretinal neovascularization. In 20 patients idiopathic focal subretinal neovascularization was characterized by a solitary focus of subretinal neovascularization at or near the fovea, associated with serous or hemorrhagic detachment of the overlying and adjacent sensory retina, or both. Although the lesions resembled the neovascular membrane seen in the presumed ocular histoplasmosis syndrome, none of the other associated characteristic ophthalmoscopic findings, considered essential to make the latter diagnosis, were apparent. In this group of patients, the incidence of positive histoplasmin skin tests was no greater than in the general population. Of the 20 patients, two had bilateral disease. In no case were there any other lesions of any kind in the afflicted or the opposite eye. The disease is self-limited over a variable period of time, but may result in extensive scarring with loss of central vision."} {"id": "PMID:1275037", "title": "Myelinated nerve fibers and severe myopia.", "content": "Two 4-year-old boys, one white and one black, had unilateral extensive myelinization of retinal nerve fibers associated with severe myopia, esotropia, and amblyopia. The finding of unilateral extensive myelinization of the nerve head and retinal fibers in a child may indicate a potentially remediable anisometropic amblyopia.", "contents": "Myelinated nerve fibers and severe myopia. Two 4-year-old boys, one white and one black, had unilateral extensive myelinization of retinal nerve fibers associated with severe myopia, esotropia, and amblyopia. The finding of unilateral extensive myelinization of the nerve head and retinal fibers in a child may indicate a potentially remediable anisometropic amblyopia."} {"id": "PMID:1275038", "title": "Rapid resolution of venous stasis retinopathy after carotid endarterectomy.", "content": "A 60-year-old woman with ocular hypertension developed unilateral venous stasis retinopathy and neovascularization of the optic disk as the first signs of carotid occlusive disease. The retinopathy and the neovascularization disappeared rapidly and dramatically after carotid endarterectomy. Neovascularization in venous stasis retinopathy must be maintained by hypoxia or hypoperfusion, possibly through some intermediate substance such as a vasoproliferative factor.", "contents": "Rapid resolution of venous stasis retinopathy after carotid endarterectomy. A 60-year-old woman with ocular hypertension developed unilateral venous stasis retinopathy and neovascularization of the optic disk as the first signs of carotid occlusive disease. The retinopathy and the neovascularization disappeared rapidly and dramatically after carotid endarterectomy. Neovascularization in venous stasis retinopathy must be maintained by hypoxia or hypoperfusion, possibly through some intermediate substance such as a vasoproliferative factor."} {"id": "PMID:1275039", "title": "Severe proliferative retinopathy as the only sign of sickle cell hemoglobin C disease.", "content": "A 48-year-old black woman developed severe bilateral hypoxic proliferative retinopathy without other clinical manifestations. The hemoglobin level was 10.6 to 11.5 g/100 ml, reticulocyte level was 2.2%, targeted and sickled red blood cells were seen on blood smears, and hemoglobins S and C were demonstrated by electrophoresis. Glucose tolerance test was normal. The development of neovascular proliferation, vitreous hemorrhage, and retinal detachment unassociated with other clinical symptoms is unusual in sickle cell hemoglobin C disease.", "contents": "Severe proliferative retinopathy as the only sign of sickle cell hemoglobin C disease. A 48-year-old black woman developed severe bilateral hypoxic proliferative retinopathy without other clinical manifestations. The hemoglobin level was 10.6 to 11.5 g/100 ml, reticulocyte level was 2.2%, targeted and sickled red blood cells were seen on blood smears, and hemoglobins S and C were demonstrated by electrophoresis. Glucose tolerance test was normal. The development of neovascular proliferation, vitreous hemorrhage, and retinal detachment unassociated with other clinical symptoms is unusual in sickle cell hemoglobin C disease."} {"id": "PMID:1275040", "title": "Cystoid macular edema in the first week after cataract extraction.", "content": "Fluorescein angiography was safely performed in 100 consecutive cases of cataract extraction during the first postoperative week. Seventy-five percent of the 100 eyes had good quality fluorescein angiograms. Four eyes demonstrated cystoid macular edema. Therefore, the incidence of cystoid macular edema in the first week after cataract surgery was low when compared to the reported incidence (40%) four to six weeks postoperatively.", "contents": "Cystoid macular edema in the first week after cataract extraction. Fluorescein angiography was safely performed in 100 consecutive cases of cataract extraction during the first postoperative week. Seventy-five percent of the 100 eyes had good quality fluorescein angiograms. Four eyes demonstrated cystoid macular edema. Therefore, the incidence of cystoid macular edema in the first week after cataract surgery was low when compared to the reported incidence (40%) four to six weeks postoperatively."} {"id": "PMID:1275041", "title": "Central corneal abscess.", "content": "Central corneal abscess developed in the experimental animal after inoculation of biologically active staphylococcal strains in a paracentral epithelial lesion of the cornea. These abscesses did not ulcerate, developed only with high inocula, occurred more frequently in immunized rabbits. A serpiginous type of ulceration did not develop at the site of the initial epithelial lesion nor at any other place in the cornea. Histologically, the lesions consisted of densely packed polymorphonuclear leukocytes between the corneal lamellae.", "contents": "Central corneal abscess. Central corneal abscess developed in the experimental animal after inoculation of biologically active staphylococcal strains in a paracentral epithelial lesion of the cornea. These abscesses did not ulcerate, developed only with high inocula, occurred more frequently in immunized rabbits. A serpiginous type of ulceration did not develop at the site of the initial epithelial lesion nor at any other place in the cornea. Histologically, the lesions consisted of densely packed polymorphonuclear leukocytes between the corneal lamellae."} {"id": "PMID:1275042", "title": "Urinary calculus during methazolamide therapy.", "content": "A 68-year-old white man with Paget's disease and open-angle glaucoma was treated with methazolamide, 50 to 100 mg three times daily. Ten months after the medication was initiated he developed ureteral colic and a calcium oxalate stone was surgically removed. Three months after the drug was reinstituted the patient passed three calcium phosphate stones. This suggested a casual relationship between methazolamide and stone formation, although renal calculi also complicate Paget's disease and acetazolamide had been administered briefly.", "contents": "Urinary calculus during methazolamide therapy. A 68-year-old white man with Paget's disease and open-angle glaucoma was treated with methazolamide, 50 to 100 mg three times daily. Ten months after the medication was initiated he developed ureteral colic and a calcium oxalate stone was surgically removed. Three months after the drug was reinstituted the patient passed three calcium phosphate stones. This suggested a casual relationship between methazolamide and stone formation, although renal calculi also complicate Paget's disease and acetazolamide had been administered briefly."} {"id": "PMID:1275043", "title": "Peripheral chorioretinal lesions and axial length of the myopic eye.", "content": "A study of the retinal periphery of 1,437 predominantly myopic eyes revealed a statistically significant association of four types of peripheral chorioretinal degenerations with increased axial length of the eye. These were white without pressure, pigmentary degeneration, pavingstone degeneration, and lattice degeneration. There was a tendency for both white without pressure and lattice degeneration jointly to affect eyes of individuals 19 years of age and younger. Increasing age was a significant factor in the incidence of pigmentary and pavingstone degenerations, whereas aging significantly reduced the prevalence of white without pressure.", "contents": "Peripheral chorioretinal lesions and axial length of the myopic eye. A study of the retinal periphery of 1,437 predominantly myopic eyes revealed a statistically significant association of four types of peripheral chorioretinal degenerations with increased axial length of the eye. These were white without pressure, pigmentary degeneration, pavingstone degeneration, and lattice degeneration. There was a tendency for both white without pressure and lattice degeneration jointly to affect eyes of individuals 19 years of age and younger. Increasing age was a significant factor in the incidence of pigmentary and pavingstone degenerations, whereas aging significantly reduced the prevalence of white without pressure."} {"id": "PMID:1275044", "title": "Vidarabine therapy of complicated herpes simplex keratitis.", "content": "Patients with active herpetic epithelial keratitis who had toxic reactions or were resistant to idoxuridine received vidarabine. Only one of 35 cases of herpetic epithelial keratitis without stromal disease failed to heal. Of 21 patients with active epithelial keratitis complicating stromal keratitis or uveitis. 11 had complete reepithelialization by day 14. Two patients were removed from the trial as treatment failures. The remaining cases healed in 21 to 48 days. In most instances the stromal keratitis was inactivated when the epithelial ulcer healed. In our patients treated with vidarabine, healing of herpes simplex epithelial ulcers was biphasic: Stage 1, progression from an active to an inactive viral ulcer, and Stage 2, complete reepithelialization.", "contents": "Vidarabine therapy of complicated herpes simplex keratitis. Patients with active herpetic epithelial keratitis who had toxic reactions or were resistant to idoxuridine received vidarabine. Only one of 35 cases of herpetic epithelial keratitis without stromal disease failed to heal. Of 21 patients with active epithelial keratitis complicating stromal keratitis or uveitis. 11 had complete reepithelialization by day 14. Two patients were removed from the trial as treatment failures. The remaining cases healed in 21 to 48 days. In most instances the stromal keratitis was inactivated when the epithelial ulcer healed. In our patients treated with vidarabine, healing of herpes simplex epithelial ulcers was biphasic: Stage 1, progression from an active to an inactive viral ulcer, and Stage 2, complete reepithelialization."} {"id": "PMID:1275045", "title": "Cyst of the intraorbital optic nerve sheaths.", "content": "A 43-year-old woman had a history of gradual unilateral visual acuity loss and proptosis. A 2.5-cm cystic dilatation of the intraorbital dura mater was removed. Microscopic examination revealed a vascular proliferation within the leptomeninges. We inadvertently injected the lesion during orbitography, providing us with an unusual radiographic appearance.", "contents": "Cyst of the intraorbital optic nerve sheaths. A 43-year-old woman had a history of gradual unilateral visual acuity loss and proptosis. A 2.5-cm cystic dilatation of the intraorbital dura mater was removed. Microscopic examination revealed a vascular proliferation within the leptomeninges. We inadvertently injected the lesion during orbitography, providing us with an unusual radiographic appearance."} {"id": "PMID:1275046", "title": "Spheno-orbital meningioma with optociliary veins.", "content": "A 40-year-old white woman had slowly progressive unilateral loss of visual acuity and increasing proptosis during an eight-year period. Ophthalmoscopy and fluorescein angiography revealed chronic disk edema and optociliary shunt vessels in the right eye. Polytomography showed an enlarged right optic canal. Cerebral arteriography demonstrated a dumbbell-shaped tumor blush in the right juxtasellar region and a diffuse tumor blush in the right orbit. Right frontal craniotomy and orbital exploration showed a cranio-orbital junction (spheno-orbital) meningioma that invaded the sclera and peripapillary choroid. Anomalous optociliary veins were demonstrated histologically at the optic disk.", "contents": "Spheno-orbital meningioma with optociliary veins. A 40-year-old white woman had slowly progressive unilateral loss of visual acuity and increasing proptosis during an eight-year period. Ophthalmoscopy and fluorescein angiography revealed chronic disk edema and optociliary shunt vessels in the right eye. Polytomography showed an enlarged right optic canal. Cerebral arteriography demonstrated a dumbbell-shaped tumor blush in the right juxtasellar region and a diffuse tumor blush in the right orbit. Right frontal craniotomy and orbital exploration showed a cranio-orbital junction (spheno-orbital) meningioma that invaded the sclera and peripapillary choroid. Anomalous optociliary veins were demonstrated histologically at the optic disk."} {"id": "PMID:1275047", "title": "Safety glasses as protection against shotgun pellets.", "content": "I designed this experiment to determine if spectacle lenses would protect against a No. 6 shot fired from a 12-gauge shotgun over progressively longer testing distances, and compared plastics, heat-tempered glass, and chemical-tempered glass lenses of standard and industrial thicknesses. The likelihood of a spectacle lens being hit by a well-centered shot pattern at 40, 50, and 60 yards was approximately 66%, 25%, and 20%, respectively. Virtually all lenses were destroyed at a testing distance of 30 yards. At 40 yards, standard-thickness plastic and heat-tempered lenses were destroyed but the chemical-tempered lenses offered some protection. At 40 yards, all types of industrial-thickness lenses provided protection but the most protection was provided by the chemical-tempered lenses. At 50 yards, chemical-tempered lenses offered more protection than either plastic or heat-tempered lenses. Throughout the experiment, plastic lenses performed no better than heat-tempered lenses.", "contents": "Safety glasses as protection against shotgun pellets. I designed this experiment to determine if spectacle lenses would protect against a No. 6 shot fired from a 12-gauge shotgun over progressively longer testing distances, and compared plastics, heat-tempered glass, and chemical-tempered glass lenses of standard and industrial thicknesses. The likelihood of a spectacle lens being hit by a well-centered shot pattern at 40, 50, and 60 yards was approximately 66%, 25%, and 20%, respectively. Virtually all lenses were destroyed at a testing distance of 30 yards. At 40 yards, standard-thickness plastic and heat-tempered lenses were destroyed but the chemical-tempered lenses offered some protection. At 40 yards, all types of industrial-thickness lenses provided protection but the most protection was provided by the chemical-tempered lenses. At 50 yards, chemical-tempered lenses offered more protection than either plastic or heat-tempered lenses. Throughout the experiment, plastic lenses performed no better than heat-tempered lenses."} {"id": "PMID:1275048", "title": "A comparison of four projection perimeters.", "content": "Identical specifications for size and luminance of the target and dome on four projection perimeters-Goldmann, Marco, Topcon, and Rodenstock- seemed to indicate that similar visual fields should be plottable with each instrument. We subjected 30 eyes to perimetry with all four machines. The Rodenstock perimeter was usually unable to map the central field with the I2e target and to identify the presence of most visual field defects. The Goldmann was most capable of demonstrating the presence of existing scotomata and was also able to plot them with the greatest definition. The Topcon was next most sensitive followed closely by the Marco. Analysis of the actual target size and luminance on each machine showed that significant variation existed and was probably responsible for the visual field differences that we found.", "contents": "A comparison of four projection perimeters. Identical specifications for size and luminance of the target and dome on four projection perimeters-Goldmann, Marco, Topcon, and Rodenstock- seemed to indicate that similar visual fields should be plottable with each instrument. We subjected 30 eyes to perimetry with all four machines. The Rodenstock perimeter was usually unable to map the central field with the I2e target and to identify the presence of most visual field defects. The Goldmann was most capable of demonstrating the presence of existing scotomata and was also able to plot them with the greatest definition. The Topcon was next most sensitive followed closely by the Marco. Analysis of the actual target size and luminance on each machine showed that significant variation existed and was probably responsible for the visual field differences that we found."} {"id": "PMID:1275049", "title": "A foot-pedal controlled valve for intraocular irrigation.", "content": "A solely mechanical foot-pedal operated valve for control of intraocular irrigation provided independence from an assistant and allowed accurate adjustment of flow. It was particularly useful during cataract aspiration, vitreous cutting, and intraocular lens implantation.", "contents": "A foot-pedal controlled valve for intraocular irrigation. A solely mechanical foot-pedal operated valve for control of intraocular irrigation provided independence from an assistant and allowed accurate adjustment of flow. It was particularly useful during cataract aspiration, vitreous cutting, and intraocular lens implantation."} {"id": "PMID:1275050", "title": "A self-retaining contact lens for slit-lamp examination of the fundus and for photocoagulation treatment.", "content": "A self-retaining contact lens for slit-lamp examination and photocoagulation treatment of the posterior fundus afforded a wide-angle view of the retina and allowed freedom of both hands of the examiner.", "contents": "A self-retaining contact lens for slit-lamp examination of the fundus and for photocoagulation treatment. A self-retaining contact lens for slit-lamp examination and photocoagulation treatment of the posterior fundus afforded a wide-angle view of the retina and allowed freedom of both hands of the examiner."} {"id": "PMID:1275054", "title": "Ultrastructure of sarcoplasmic reticulum in atrial myocardium of patients with mitral valvular disease.", "content": "Alterations observed in the sarcoplasmic reticulum of muscle cells in left and right atrial myocardium from 10 patients with mitral valvular disease consisted of: a) proliferation of rough-surfaced endoplasmic reticulum, which formed large cisterns in perinuclear areas of hypertrophied cells and was considered indicative of increased protein synthesis; b) proliferation of free sarcoplasmic reticulum, a change that occurred in degenerated cells and appeared to be related to loss of contractile elements; c) two types of aggregates of tubules of free SR--one type was associated wtih abnormal Z-band material and was found only in cells showing loss of myofibrils and proliferation of free SR, whereas the other was not associated with either of these changes and occurred in less severely altered cells; and d) proliferation and enlargement of cisterns of extended junctional sarcoplasmic reticulum, which formed two distinct types of complexes: the first of these consisted of large, convoluted (Type A) cisterns that were wide (550 to 650 A in thickness) and did not have a central dense lamina; the second was composed of stacks of concentric or parallel (Type B) cisterns that were narrower (220 to 300 A in thickness), had a central dense lamina, and were separated from one another by layers of glycogen granules. The formation of these complexes of cisterns was regarded as an extreme form of overdevelopment of extended junctional sarcoplasmic reticulum in atrial muscle cells.", "contents": "Ultrastructure of sarcoplasmic reticulum in atrial myocardium of patients with mitral valvular disease. Alterations observed in the sarcoplasmic reticulum of muscle cells in left and right atrial myocardium from 10 patients with mitral valvular disease consisted of: a) proliferation of rough-surfaced endoplasmic reticulum, which formed large cisterns in perinuclear areas of hypertrophied cells and was considered indicative of increased protein synthesis; b) proliferation of free sarcoplasmic reticulum, a change that occurred in degenerated cells and appeared to be related to loss of contractile elements; c) two types of aggregates of tubules of free SR--one type was associated wtih abnormal Z-band material and was found only in cells showing loss of myofibrils and proliferation of free SR, whereas the other was not associated with either of these changes and occurred in less severely altered cells; and d) proliferation and enlargement of cisterns of extended junctional sarcoplasmic reticulum, which formed two distinct types of complexes: the first of these consisted of large, convoluted (Type A) cisterns that were wide (550 to 650 A in thickness) and did not have a central dense lamina; the second was composed of stacks of concentric or parallel (Type B) cisterns that were narrower (220 to 300 A in thickness), had a central dense lamina, and were separated from one another by layers of glycogen granules. The formation of these complexes of cisterns was regarded as an extreme form of overdevelopment of extended junctional sarcoplasmic reticulum in atrial muscle cells."} {"id": "PMID:1275055", "title": "The alveolar macrophage delivery system. Kinetic studies in cultured explants of murine lung.", "content": "The production of alveolar macrophages in a blood-free organ culture system has been studied to determine whether free macrophages undergo mitosis or whether their ongoing production is dependent upon continuing division of interstitial cells. Explants of murine long were attached to cellophane or glass; after 6 days of culture, a population of cells identified morphologically and functionally as macrophages appeared around the central tissue. These cells did not divide, and they disappeared 4 days after removal of the central lung explant. 3H-thymidine labeling of these peripheral macrophages was observed only when the central tissue was present and when the thymidine pulse was 24 hours in duration. Actual cell division was observed only in the interstitial cells of the explant. It is concluded that the interstitial cell population provides a continuing pool of precursor cells that divide and migrate outwards, creating a \"steady state\" system in which macrophage loss at the periphery is balanced by cell production at the center.", "contents": "The alveolar macrophage delivery system. Kinetic studies in cultured explants of murine lung. The production of alveolar macrophages in a blood-free organ culture system has been studied to determine whether free macrophages undergo mitosis or whether their ongoing production is dependent upon continuing division of interstitial cells. Explants of murine long were attached to cellophane or glass; after 6 days of culture, a population of cells identified morphologically and functionally as macrophages appeared around the central tissue. These cells did not divide, and they disappeared 4 days after removal of the central lung explant. 3H-thymidine labeling of these peripheral macrophages was observed only when the central tissue was present and when the thymidine pulse was 24 hours in duration. Actual cell division was observed only in the interstitial cells of the explant. It is concluded that the interstitial cell population provides a continuing pool of precursor cells that divide and migrate outwards, creating a \"steady state\" system in which macrophage loss at the periphery is balanced by cell production at the center."} {"id": "PMID:1275056", "title": "Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma.", "content": "The syndrome of familial medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia is inherited as an autosomal dominant trait, and is characterized by development of bilateral and multicentric thyroidal and adrenal medullary tumors. One of the earliest manifestations of adrenal medullary hyperfunction in patients with this syndrome is an increased ratio of epinephrine to norepinephrine in urine. In order to define the morphologic correlates of these early catecholamine abnormalities in a large kindred with familial MTC, a morphometric analysis based on a point-counting system to asses adrenal medullary volume was undertaken. These studies clearly revealed adrenal medullary hyperplasia as reflected by a two- to three-fold increase in medullary volume and weight as compared to age- and sex-matched controls. The increase in total medullary mass resulted from diffuse and multifocal modular proliferations of adrenal medullary cells primarily within the head and body regions of the glands. These results support the hypothesis that the pheochromocytomas in patients with familial MTC may, in fact, represent extreme degrees of nodular hyperplasia of the medulla.", "contents": "Adrenal medullary hyperplasia. A morphometric analysis in patients with familial medullary thyroid carcinoma. The syndrome of familial medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia is inherited as an autosomal dominant trait, and is characterized by development of bilateral and multicentric thyroidal and adrenal medullary tumors. One of the earliest manifestations of adrenal medullary hyperfunction in patients with this syndrome is an increased ratio of epinephrine to norepinephrine in urine. In order to define the morphologic correlates of these early catecholamine abnormalities in a large kindred with familial MTC, a morphometric analysis based on a point-counting system to asses adrenal medullary volume was undertaken. These studies clearly revealed adrenal medullary hyperplasia as reflected by a two- to three-fold increase in medullary volume and weight as compared to age- and sex-matched controls. The increase in total medullary mass resulted from diffuse and multifocal modular proliferations of adrenal medullary cells primarily within the head and body regions of the glands. These results support the hypothesis that the pheochromocytomas in patients with familial MTC may, in fact, represent extreme degrees of nodular hyperplasia of the medulla."} {"id": "PMID:1275058", "title": "Lipid accumulation in human aortic smooth muscle cell lysosomes.", "content": "Lipid deposition is a central feature of the human atherosclerotic lesion. Deficient lysosomal lipolytic activity has been implicated as a pathogenetic factor in atheroma formation. Cytochemical and ultrastructural examination of the abdominal aortas of 2 normal young males, ages 11 and 23, demonstrates lipid accumulation with lysosomes of intact mural smooth muscle cells. This appears to be an early stage in the process which eventually results in an overloading of lysosomes and the formation of lipid-laden foam cells.", "contents": "Lipid accumulation in human aortic smooth muscle cell lysosomes. Lipid deposition is a central feature of the human atherosclerotic lesion. Deficient lysosomal lipolytic activity has been implicated as a pathogenetic factor in atheroma formation. Cytochemical and ultrastructural examination of the abdominal aortas of 2 normal young males, ages 11 and 23, demonstrates lipid accumulation with lysosomes of intact mural smooth muscle cells. This appears to be an early stage in the process which eventually results in an overloading of lysosomes and the formation of lipid-laden foam cells."} {"id": "PMID:1275059", "title": "Endocytosis by vascular smooth muscle cells in vivo and in vitro. Roles or vesicles and lysosomes.", "content": "Overloading of lysosomes of smooth muscle cells with excess substrate may be a key event in the development of hypertensive and atherosclerotic vascular disease. Cellular uptake of materials and its relation to lysosomal function were studied by ultrastructural cytochemistry in aortic smooth muscle cells grown in vitro and in the intact animal. Injection of horseradish peroxidase (HRP) into hypertensive rats resulted in rapid insudation of the material into the environs of medial smooth muscle cells, entrance into surface pinocytic vesicles, and transport via vesicles into the cell interior where material was seen to accumulate within lysosomes. In vitro exposure of calf aortic cells to HRP in the medium resulted in a similar sequence of events. Pinocytic vesicles, seen both in vitro and in vivo, ranged in diameter from 650-1000 A. These dimensions are adequate to permit incorporation of intact lipoproteins of all classes, except the larger chylomicrons.", "contents": "Endocytosis by vascular smooth muscle cells in vivo and in vitro. Roles or vesicles and lysosomes. Overloading of lysosomes of smooth muscle cells with excess substrate may be a key event in the development of hypertensive and atherosclerotic vascular disease. Cellular uptake of materials and its relation to lysosomal function were studied by ultrastructural cytochemistry in aortic smooth muscle cells grown in vitro and in the intact animal. Injection of horseradish peroxidase (HRP) into hypertensive rats resulted in rapid insudation of the material into the environs of medial smooth muscle cells, entrance into surface pinocytic vesicles, and transport via vesicles into the cell interior where material was seen to accumulate within lysosomes. In vitro exposure of calf aortic cells to HRP in the medium resulted in a similar sequence of events. Pinocytic vesicles, seen both in vitro and in vivo, ranged in diameter from 650-1000 A. These dimensions are adequate to permit incorporation of intact lipoproteins of all classes, except the larger chylomicrons."} {"id": "PMID:1275060", "title": "Sodium balance and the natriuresis of hypertonic saline infusion in dogs.", "content": "Recently, a paradoxical effect of dietary salt intake on the natriuresis following hypertonic saline infusion was observed in rats. In these experiments the effects of alterations in dietary sodium on the natriuretic response to a hypertonic saline load was studied in dogs. Dogs maintained on a high-sodium diet did not have a significantly different natriuresis than those on a low-sodium diet. When differences in sodium balance were amplified by the use of deoxycorticosterone, furosemide, and manipulation of dietary sodium, dogs in positive sodium balance showed a significantly enhanced initial excretion of sodium followed by a reversal of the pattern. Consequently, the cumulative sodium excretion was not different between low- and high-sodium groups. Since the cumulative natriuretic response to isotonic saline infusion was larger in dogs in positive sodium balance compared to those in negative sodium balance, the failure to detect a difference following hypertonic saline infusion was probably because of the increased plasma sodium concentration.", "contents": "Sodium balance and the natriuresis of hypertonic saline infusion in dogs. Recently, a paradoxical effect of dietary salt intake on the natriuresis following hypertonic saline infusion was observed in rats. In these experiments the effects of alterations in dietary sodium on the natriuretic response to a hypertonic saline load was studied in dogs. Dogs maintained on a high-sodium diet did not have a significantly different natriuresis than those on a low-sodium diet. When differences in sodium balance were amplified by the use of deoxycorticosterone, furosemide, and manipulation of dietary sodium, dogs in positive sodium balance showed a significantly enhanced initial excretion of sodium followed by a reversal of the pattern. Consequently, the cumulative sodium excretion was not different between low- and high-sodium groups. Since the cumulative natriuretic response to isotonic saline infusion was larger in dogs in positive sodium balance compared to those in negative sodium balance, the failure to detect a difference following hypertonic saline infusion was probably because of the increased plasma sodium concentration."} {"id": "PMID:1275061", "title": "Thyroid function in a hibernator, Spermophilus tridecemlineatus.", "content": "Thyroid hormone secretion (assessed as thyroid 125I release rate) was monitored in Spermophilus tridecemlineatus from summer to winter (July-December) in 1973. The average release rate in July was 2.3% per day, but in August this rate decreased significantly and remained at an average 0.52% per day until December. This low rate (being similar to that of hypophysectomized rats), and the absence of any change in oxygen consumption following thyroidectomy, suggested hormone secretion was \"turned off\" during this period. During the period August-December, four S. tridecemlineatus showed normal thermoregulatory responses to anterior hypothalamic cooling but no thyroidal response whether restrained, unrestrained, or anesthetized. Thyroid 125I uptake (and presumably hormone manufacture) continued during the period August-December and 24-h uptake averaged 27.0% in December. Possible reasons for \"turning off\" thyroid hormone secretion are discussed, and it is concluded this is to allow the membrane fatty acids to revert to a less-saturated condition in preparation for low body temperatures during hibernation.", "contents": "Thyroid function in a hibernator, Spermophilus tridecemlineatus. Thyroid hormone secretion (assessed as thyroid 125I release rate) was monitored in Spermophilus tridecemlineatus from summer to winter (July-December) in 1973. The average release rate in July was 2.3% per day, but in August this rate decreased significantly and remained at an average 0.52% per day until December. This low rate (being similar to that of hypophysectomized rats), and the absence of any change in oxygen consumption following thyroidectomy, suggested hormone secretion was \"turned off\" during this period. During the period August-December, four S. tridecemlineatus showed normal thermoregulatory responses to anterior hypothalamic cooling but no thyroidal response whether restrained, unrestrained, or anesthetized. Thyroid 125I uptake (and presumably hormone manufacture) continued during the period August-December and 24-h uptake averaged 27.0% in December. Possible reasons for \"turning off\" thyroid hormone secretion are discussed, and it is concluded this is to allow the membrane fatty acids to revert to a less-saturated condition in preparation for low body temperatures during hibernation."} {"id": "PMID:1275062", "title": "Compensatory adaptation of sodium and bicarbonate excretion: effect of diuretics.", "content": "Complete clamping of the contralateral kidney results in a rapid and significant increase in the fractional excretion of Na, K, and bicarbonate by the remaining kidney during bicarbonate loading. Similar studies were performed in dogs after administration of diuretics with different major sites of action to localize the adaptive excretory response to acute reduction in renal mass. Volume expansion was carefully avoided. In experiments with the loop inhibitor, furosemide, contralateral kidney clamping rapidly and significantly increased fractional excretion of Na and bicarbonate. A more delayed and smaller response was observed in dogs given hydrochlorothiazide. Acetazolamide, a potent inhibitor of proximal Na bicarbonate reabsorption, completely blocked the excretory response to contralateral kidney clamping. The enhanced response with furosemide and its blockade with acetazolamide indicates a proximal site of adaptation to acute contralateral kidney exclusion. The overall natriuretic response depends on the level of inhibition of loop reabsorption.", "contents": "Compensatory adaptation of sodium and bicarbonate excretion: effect of diuretics. Complete clamping of the contralateral kidney results in a rapid and significant increase in the fractional excretion of Na, K, and bicarbonate by the remaining kidney during bicarbonate loading. Similar studies were performed in dogs after administration of diuretics with different major sites of action to localize the adaptive excretory response to acute reduction in renal mass. Volume expansion was carefully avoided. In experiments with the loop inhibitor, furosemide, contralateral kidney clamping rapidly and significantly increased fractional excretion of Na and bicarbonate. A more delayed and smaller response was observed in dogs given hydrochlorothiazide. Acetazolamide, a potent inhibitor of proximal Na bicarbonate reabsorption, completely blocked the excretory response to contralateral kidney clamping. The enhanced response with furosemide and its blockade with acetazolamide indicates a proximal site of adaptation to acute contralateral kidney exclusion. The overall natriuretic response depends on the level of inhibition of loop reabsorption."} {"id": "PMID:1275063", "title": "Electrolyte transport in remnant kidney of the dog: effect of furosemide.", "content": "Micropuncture studies were performed in 26 dogs with a unilateral remnant kidney to examine its response to modest extracellular volume expansion and furosemide administration in the presence (Stage II) and absence (Stage III) of an intact contralateral kidney. During hydropenia in 15 Stage II dogs, proximal and distal transport of sodium and potassium was comparable to that of normal dogs (Stage I). Following 3% volume expansion, fractional proximal reabsorption was reduced similarly in Stages I and II. Although a slightly greater reduction in fractional loop reabsorption of sodium in Stage II after volume expansion was not significant, it was significantly greater with furosemide administration. In 11 Stage III dogs, proximal fractional reabsorption was depressed during hydropenia, and the loop sodium response to both volume expansion and furosemide administration was exaggerated. In contrast, greater increase in distal potassium secretion was demonstrated mainly in Stage III but not in Stage II remnant kidneys both before and after the diuretic maneuvers. The observations of exaggerated sodium response to furosemide by the remnant kidney in both Stages II and III but greater potassium response only in Stage III suggest that independent factors are responsible for these adaptations when functioning renal mass is reduced.", "contents": "Electrolyte transport in remnant kidney of the dog: effect of furosemide. Micropuncture studies were performed in 26 dogs with a unilateral remnant kidney to examine its response to modest extracellular volume expansion and furosemide administration in the presence (Stage II) and absence (Stage III) of an intact contralateral kidney. During hydropenia in 15 Stage II dogs, proximal and distal transport of sodium and potassium was comparable to that of normal dogs (Stage I). Following 3% volume expansion, fractional proximal reabsorption was reduced similarly in Stages I and II. Although a slightly greater reduction in fractional loop reabsorption of sodium in Stage II after volume expansion was not significant, it was significantly greater with furosemide administration. In 11 Stage III dogs, proximal fractional reabsorption was depressed during hydropenia, and the loop sodium response to both volume expansion and furosemide administration was exaggerated. In contrast, greater increase in distal potassium secretion was demonstrated mainly in Stage III but not in Stage II remnant kidneys both before and after the diuretic maneuvers. The observations of exaggerated sodium response to furosemide by the remnant kidney in both Stages II and III but greater potassium response only in Stage III suggest that independent factors are responsible for these adaptations when functioning renal mass is reduced."} {"id": "PMID:1275064", "title": "Neuromuscular function at hyperbaric pressures: pressure-anesthetic interactions.", "content": "Hydrostatic pressure and anesthetic agents exert mutually antagonistic effects, including pressure reversal of anesthesia and anesthetic amelioration of the high-pressure nervous syndrome. To clarify the cellular basis for these phenomena, twitch tension and electromyogram (EMG) were monitored in the indirectly stimulated isolated rat diaphragm. Compression to 137 atm increased twitch tension without changing EMG amplitude. Partial phrenic nerve block accompanied EMG depression induced by methoxyflurane and chloroform; pressure antagonized these effects. To examine subthreshold pressure effects, calcium concentration was decreased from 2.5 to 0.5 mM. Compression to 137 atm then reversibly decreased EMG amplitude, while enhancing twitch tension. In 0.5 mM calcium, methoxyflurane and chloroform depressed EMG amplitude before blocking phrenic nerve conduction; pressure to 137 atm produced additional depression. These results suggest that pressure enhances twitch tension by acting on excitation-contraction coupling or on the contractile mechanism. They also indicate that pressure may inhibit transmission at the neuromuscular junction, and they do not support synaptic transmission as a site of pressure-anesthetic antagonism.", "contents": "Neuromuscular function at hyperbaric pressures: pressure-anesthetic interactions. Hydrostatic pressure and anesthetic agents exert mutually antagonistic effects, including pressure reversal of anesthesia and anesthetic amelioration of the high-pressure nervous syndrome. To clarify the cellular basis for these phenomena, twitch tension and electromyogram (EMG) were monitored in the indirectly stimulated isolated rat diaphragm. Compression to 137 atm increased twitch tension without changing EMG amplitude. Partial phrenic nerve block accompanied EMG depression induced by methoxyflurane and chloroform; pressure antagonized these effects. To examine subthreshold pressure effects, calcium concentration was decreased from 2.5 to 0.5 mM. Compression to 137 atm then reversibly decreased EMG amplitude, while enhancing twitch tension. In 0.5 mM calcium, methoxyflurane and chloroform depressed EMG amplitude before blocking phrenic nerve conduction; pressure to 137 atm produced additional depression. These results suggest that pressure enhances twitch tension by acting on excitation-contraction coupling or on the contractile mechanism. They also indicate that pressure may inhibit transmission at the neuromuscular junction, and they do not support synaptic transmission as a site of pressure-anesthetic antagonism."} {"id": "PMID:1275065", "title": "Evidence for active chloride transport in dogfish rectal gland.", "content": "To evaluate the characteristics of the transport process for Na and C1 by the rectal gland of the dogfish shark, experiments were performed with an in vitro perfused model. Changes in glandular secretion rate and net electrical potential difference (PD) were measured during independent alterations of the Na and C1 concentrations of the perfusate solution. The rate of net secretion was enhanced by increasing the concentration of either Na or Cl in the perfusate, demonstrating a substratedependent process. When tetramethyl-ammonium was substituted for Na, the rate of secretion fell in association with a rise in net PD from -8 mV to -17 mV (lumen negative). When SO4 was substituted for Cl, secretion rate also fell, but in association with a fall in net PD. Despite almost complete replacement of Cl with SO4, net PD was not reversed. Although the mechanism responsible for Na secretion remains unclear, these data suggest that chloride is transported by an active process in the dogfish rectal gland.", "contents": "Evidence for active chloride transport in dogfish rectal gland. To evaluate the characteristics of the transport process for Na and C1 by the rectal gland of the dogfish shark, experiments were performed with an in vitro perfused model. Changes in glandular secretion rate and net electrical potential difference (PD) were measured during independent alterations of the Na and C1 concentrations of the perfusate solution. The rate of net secretion was enhanced by increasing the concentration of either Na or Cl in the perfusate, demonstrating a substratedependent process. When tetramethyl-ammonium was substituted for Na, the rate of secretion fell in association with a rise in net PD from -8 mV to -17 mV (lumen negative). When SO4 was substituted for Cl, secretion rate also fell, but in association with a fall in net PD. Despite almost complete replacement of Cl with SO4, net PD was not reversed. Although the mechanism responsible for Na secretion remains unclear, these data suggest that chloride is transported by an active process in the dogfish rectal gland."} {"id": "PMID:1275066", "title": "Intestinal calcium absorption: differences in transport between duodenum and ileum.", "content": "The interaction of calcium with sugar, sodium, and water absorption was studied in rats fed laboratory chow and in vitamin D-deficient and -repleted rats with the use of intestinal loops in vivo. Calcium absorption in the duodenum was enhanced by D-glucose only in the vitamin D-deficient state. In both vitamin D-deficient and -repleted ileum, calcium absorption decreased when NaCl was replaced by mannitol; however, it remained unchanged when NaCl was replaced by choline chloride or urea. Calcium absorption was enhanced by actively transported sugars and by increasing net water flow generated by differences in osmotic pressure and urea. Under all experimental conditions there was a strong association between net water and calcium absorption in the ileum. These findings suggest that calcium absorption is enhanced by solvent drag, although the role of sodium cannot be excluded entirely.", "contents": "Intestinal calcium absorption: differences in transport between duodenum and ileum. The interaction of calcium with sugar, sodium, and water absorption was studied in rats fed laboratory chow and in vitamin D-deficient and -repleted rats with the use of intestinal loops in vivo. Calcium absorption in the duodenum was enhanced by D-glucose only in the vitamin D-deficient state. In both vitamin D-deficient and -repleted ileum, calcium absorption decreased when NaCl was replaced by mannitol; however, it remained unchanged when NaCl was replaced by choline chloride or urea. Calcium absorption was enhanced by actively transported sugars and by increasing net water flow generated by differences in osmotic pressure and urea. Under all experimental conditions there was a strong association between net water and calcium absorption in the ileum. These findings suggest that calcium absorption is enhanced by solvent drag, although the role of sodium cannot be excluded entirely."} {"id": "PMID:1275067", "title": "Effects of anoxia and glucose depletion on isolated veins of the dog.", "content": "Canine vein strips were mounted for isometric tension recording. Anoxia did not affect basal tension of saphenous and pulmonary strips mounted in standard Krebs-Ringer solution or after 30 min of incubation in glucose-free solution. Anoxia depressed the strength of spontaneous contractions of mesenteric veins; in glucose-free solution (30 min), anoxia relaxed the strips. Veins placed in glucose-free solution for more than 60 min contracted with anoxia; this contraction was not inhibited by iproveratril. When the vein strips were contracted by norepinephrine or KCl, anoxia depressed the contractions, most in mesenteric and least in saphenous preparations; this depression was greater in the absence of glucose. When oxygen was present, the absence of glucose had little effect on the response to vasoactive agents. Contractions with acetylcholine were depressed by anoxia in mesenteric and pulmonary strips but were augmented in saphenous veins; the latter potentiation was inhibited by iproveratril and by incubation in glucose-free solution. Thus, especially in the saphenous vein, anaerobic glycolysis can provide most of the energy requirements, and intracellular substrates are available for oxidative metabolism.", "contents": "Effects of anoxia and glucose depletion on isolated veins of the dog. Canine vein strips were mounted for isometric tension recording. Anoxia did not affect basal tension of saphenous and pulmonary strips mounted in standard Krebs-Ringer solution or after 30 min of incubation in glucose-free solution. Anoxia depressed the strength of spontaneous contractions of mesenteric veins; in glucose-free solution (30 min), anoxia relaxed the strips. Veins placed in glucose-free solution for more than 60 min contracted with anoxia; this contraction was not inhibited by iproveratril. When the vein strips were contracted by norepinephrine or KCl, anoxia depressed the contractions, most in mesenteric and least in saphenous preparations; this depression was greater in the absence of glucose. When oxygen was present, the absence of glucose had little effect on the response to vasoactive agents. Contractions with acetylcholine were depressed by anoxia in mesenteric and pulmonary strips but were augmented in saphenous veins; the latter potentiation was inhibited by iproveratril and by incubation in glucose-free solution. Thus, especially in the saphenous vein, anaerobic glycolysis can provide most of the energy requirements, and intracellular substrates are available for oxidative metabolism."} {"id": "PMID:1275068", "title": "Carbohydrate metabolism in fetal and neonatal rat brain during anoxia and recovery.", "content": "Systemic and cerebral metabolic responses to acute anoxia were studied in term-fetal and neonatal rats in order to account for the greater anoxic tolerance of fetuses. Measurements of blood acid-base balance were correlated with changes in the concentrations of adenine nucleotides, creatine, phosphocreatine, and glycogen in brain, and of glucose, pyruvate, and lactate in brain, blood, and cerebrospinal fluid during 1) exposure (20-40 min) to 100% nitrogen at 37 degrees C, and 2) subsequent recovery in air. Blood PCO2 was higher initially in fetuses and increased more rapidly during anoxia in fetuses than in neonates, exceeding 150 mmHg after 20 min. Brain glycogen, phosphocreatine, and total adenine nucleotides declined more slowly in fetuses than in neonates during anoxia, whereas brain glucose levels declined at similar rates in the two groups. From the changes in these preformed and potential energy stores, it was estimated that total cerebral energy consumption during anoxia was significantly lower in fetuses. The data suggest that the more severe hypercapnia superimposed on anoxia in fetuses decreased cerebral metabolic demands, and thus prolonged survival. An incidental finding was that L-lactate readily enters the immature brain from the blood during anoxia, and in the early recovery phase may constitute the preferred substrate for cerebral oxidative metabolism, sparing glucose.", "contents": "Carbohydrate metabolism in fetal and neonatal rat brain during anoxia and recovery. Systemic and cerebral metabolic responses to acute anoxia were studied in term-fetal and neonatal rats in order to account for the greater anoxic tolerance of fetuses. Measurements of blood acid-base balance were correlated with changes in the concentrations of adenine nucleotides, creatine, phosphocreatine, and glycogen in brain, and of glucose, pyruvate, and lactate in brain, blood, and cerebrospinal fluid during 1) exposure (20-40 min) to 100% nitrogen at 37 degrees C, and 2) subsequent recovery in air. Blood PCO2 was higher initially in fetuses and increased more rapidly during anoxia in fetuses than in neonates, exceeding 150 mmHg after 20 min. Brain glycogen, phosphocreatine, and total adenine nucleotides declined more slowly in fetuses than in neonates during anoxia, whereas brain glucose levels declined at similar rates in the two groups. From the changes in these preformed and potential energy stores, it was estimated that total cerebral energy consumption during anoxia was significantly lower in fetuses. The data suggest that the more severe hypercapnia superimposed on anoxia in fetuses decreased cerebral metabolic demands, and thus prolonged survival. An incidental finding was that L-lactate readily enters the immature brain from the blood during anoxia, and in the early recovery phase may constitute the preferred substrate for cerebral oxidative metabolism, sparing glucose."} {"id": "PMID:1275069", "title": "Use of pyrazinamide to assess renal uric acid transport in the rat: a micropuncture study.", "content": "Free-flow micropuncture studies were performed to evaluate renal uric acid transport in control and pyrazinamide-treated rats. In all studies [2-14C]uric acid and [methoxy-3H]inulin were administered. [2-14C]uric acid was determined after column chromatographic separation from its labeled oxidation product in tubular fluid, plasma, and urine. Tubular fluid collections were obtained from the early and late proximal tubule under hydropenic conditions and from the early proximal tubule during volume expansion induced with 0.9% sodium chloride. These studies indicate that pyrazinamide, in the dose employed, provokes a uniform reduction in fractional uric acid excretion but simultaneously inhibits both net uric acid reabsorption and secretion in the early and late proximal tubule, respectively. In addition, these experiments unmasked uric acid reabsorption within the late proximal tubule and bidirectional transport beyond this nephron site. These studies also suggest at least two mechanisms for uric acid reabsorption; one sodium dependent, the other independent of sodium and water transport.", "contents": "Use of pyrazinamide to assess renal uric acid transport in the rat: a micropuncture study. Free-flow micropuncture studies were performed to evaluate renal uric acid transport in control and pyrazinamide-treated rats. In all studies [2-14C]uric acid and [methoxy-3H]inulin were administered. [2-14C]uric acid was determined after column chromatographic separation from its labeled oxidation product in tubular fluid, plasma, and urine. Tubular fluid collections were obtained from the early and late proximal tubule under hydropenic conditions and from the early proximal tubule during volume expansion induced with 0.9% sodium chloride. These studies indicate that pyrazinamide, in the dose employed, provokes a uniform reduction in fractional uric acid excretion but simultaneously inhibits both net uric acid reabsorption and secretion in the early and late proximal tubule, respectively. In addition, these experiments unmasked uric acid reabsorption within the late proximal tubule and bidirectional transport beyond this nephron site. These studies also suggest at least two mechanisms for uric acid reabsorption; one sodium dependent, the other independent of sodium and water transport."} {"id": "PMID:1275070", "title": "Changes in body temperature produced by prostaglandins and pyrogens in the chicken.", "content": "Bacterial pyrogen from S. abortus equi (SAE) was injected into the wing veins of chickens. Following injection of 0.05-0.5 mug SAE, body temperatures did not change significantly, whereas 2.0 or 10 mug of pyrogen caused falls in body temperature of 0.56 +/- 0.10degrees C and 1.1 +/- 0.21degrees C (mean +/- SE, n=5). The temperature falls were accompanied by a flushing of the comb and an increase in respiratory rate and were not antagonized by 1.0 g of acetylsalicylic acid (ASA) given orally. The injection of SAE (0.1 mug in 1 mul) into the anterior hypothalamus produced fevers averaging 1.24 +/- 0.07 degrees C (n=9) which were antagonized by oral ASA. Injections of SAE at other brainstem loci produced no temperatur changes. Seven chickens were also injected with 0.1 mug PGE in 1.0 mul into the anterior hypothalamus, and they developed fevers averaging 0.90 +/- 0.16 degrees C. The results support the concept that prostaglandins may be involved in fever in chickens but suggest that the action of pyrogen injected intravenously may be different from that following its injection directly into the hypothalamus.", "contents": "Changes in body temperature produced by prostaglandins and pyrogens in the chicken. Bacterial pyrogen from S. abortus equi (SAE) was injected into the wing veins of chickens. Following injection of 0.05-0.5 mug SAE, body temperatures did not change significantly, whereas 2.0 or 10 mug of pyrogen caused falls in body temperature of 0.56 +/- 0.10degrees C and 1.1 +/- 0.21degrees C (mean +/- SE, n=5). The temperature falls were accompanied by a flushing of the comb and an increase in respiratory rate and were not antagonized by 1.0 g of acetylsalicylic acid (ASA) given orally. The injection of SAE (0.1 mug in 1 mul) into the anterior hypothalamus produced fevers averaging 1.24 +/- 0.07 degrees C (n=9) which were antagonized by oral ASA. Injections of SAE at other brainstem loci produced no temperatur changes. Seven chickens were also injected with 0.1 mug PGE in 1.0 mul into the anterior hypothalamus, and they developed fevers averaging 0.90 +/- 0.16 degrees C. The results support the concept that prostaglandins may be involved in fever in chickens but suggest that the action of pyrogen injected intravenously may be different from that following its injection directly into the hypothalamus."} {"id": "PMID:1275071", "title": "Neurophysiological studies on central chemosensor in medullary ventrolateral areas.", "content": "Nonphasic unit potentials were recorded with glass microelectrodes from the ventrolateral medullary areas in spontaneously breathing cats. The firing rate changes were studied during metabolic acidosis and alkalosis induced by intravenous injections of 4 ml 0.1 N HCl and molar NaHCO3, respectively, and during CO2 rebreathing. Three groups of units were distinguished among 44 neurons: 1) 9 U were markedly sensitive to variations in acid-base parameters; each reacted in the opposite manner upon acidosis and alkalosis, and these reactions were reproducible. 2) Twelve units were responsive to touch of a contralateral limb with a prompt and massive rise in firing rate. 3) The remaining 23 U were classified as nonsensitive to any of the stimuli applied. All these 44 U were found to be intermingled. It is possible that the chemosensitive cells found may be part of the central chemosensor.", "contents": "Neurophysiological studies on central chemosensor in medullary ventrolateral areas. Nonphasic unit potentials were recorded with glass microelectrodes from the ventrolateral medullary areas in spontaneously breathing cats. The firing rate changes were studied during metabolic acidosis and alkalosis induced by intravenous injections of 4 ml 0.1 N HCl and molar NaHCO3, respectively, and during CO2 rebreathing. Three groups of units were distinguished among 44 neurons: 1) 9 U were markedly sensitive to variations in acid-base parameters; each reacted in the opposite manner upon acidosis and alkalosis, and these reactions were reproducible. 2) Twelve units were responsive to touch of a contralateral limb with a prompt and massive rise in firing rate. 3) The remaining 23 U were classified as nonsensitive to any of the stimuli applied. All these 44 U were found to be intermingled. It is possible that the chemosensitive cells found may be part of the central chemosensor."} {"id": "PMID:1275072", "title": "Michaelis-Menten kinetics of galactose elimination by the isolated perfused pig liver.", "content": "The relation between galactose elimination rates and blood concentrations in the isolated perfused pig liver was analyzed by a mathematical kinetic model. It assumes that the substrate, under steady-state conditions, is removed from the blood that flows through the sinusoids by an irreversible process which follows Michaelis-Menten (i.e., saturation) kinetics. The experiments consisted of successive periods with constant infusions of galactose. The model fitted the data to within the experimental uncertainty. The estimated maximal rate (Vmax) ranged from 0.34 to 0.57 mmol-min(-1)-kg(-1) liver, and the Michaelis constant, Km, ranged from 0.12 to 0.30 mmol-liter(-1) plasma water in nine experiments. The ratio between the galactose concentration in hepatocyte water and plasma water was not significantly different from 1.0, indicating that membrane transport is not rate limiting for the elimination of galactose. In experiments with increasing concentrations of galactose in hepatocyte water and approximately saturated elimination rates, the concentrations of galactose 1-phosphate, UDPgalactose, and UDPglucose remained essentially constant. This indicates that the phosphorylation of galactose to galactose 1-phosphate is the rate-determining process.", "contents": "Michaelis-Menten kinetics of galactose elimination by the isolated perfused pig liver. The relation between galactose elimination rates and blood concentrations in the isolated perfused pig liver was analyzed by a mathematical kinetic model. It assumes that the substrate, under steady-state conditions, is removed from the blood that flows through the sinusoids by an irreversible process which follows Michaelis-Menten (i.e., saturation) kinetics. The experiments consisted of successive periods with constant infusions of galactose. The model fitted the data to within the experimental uncertainty. The estimated maximal rate (Vmax) ranged from 0.34 to 0.57 mmol-min(-1)-kg(-1) liver, and the Michaelis constant, Km, ranged from 0.12 to 0.30 mmol-liter(-1) plasma water in nine experiments. The ratio between the galactose concentration in hepatocyte water and plasma water was not significantly different from 1.0, indicating that membrane transport is not rate limiting for the elimination of galactose. In experiments with increasing concentrations of galactose in hepatocyte water and approximately saturated elimination rates, the concentrations of galactose 1-phosphate, UDPgalactose, and UDPglucose remained essentially constant. This indicates that the phosphorylation of galactose to galactose 1-phosphate is the rate-determining process."} {"id": "PMID:1275073", "title": "Lateralized phrenic nerve responses to stimulating respiratory afferents in the cat.", "content": "We stimulated electrically pharyngeal branch of both glossopharyngeal nerves (PGLN), internal branch of superior laryngeal nerves (ISLN), and carotid sinus nerves (CSN) in anesthetized cats. We recorded simultaneously, averaged, and compared bilaterally evoked phrenic nerve (PHR) activity. Our objective was to demonstrate a short-latency evoked response in the PHR contralateral to the stimulus. Low-intensity stimulation of PGLN and ISLN during inspiration evoked a short-latency contralateral excitation with a latency of 5.2 ms +/- 0.2 SE (16 cats) for PGLN, and 3.8 ms +/- 0.1 SE (13 cats) for ISLN. This excitation could follow stimuli delivered at 100 Hz. Stimulation during expiration did not result in a lateralized excitation. The excitation is followed by bilateral inhibition. Neither strychnine nor picrotoxin prevented either the lateralized response or the inhibition, though strychnine diminished a delayed bilateral excitation following PGLN stimulation. This dalayed (latency 18.7 ms +/- 0.7 SE) bilateral excitation corresponds to the sniff reflex. CSN stimulation did not result in lateralized excitation. We suggest that the lateralized evoked response results from a gated paucisynaptic reflex pathway involving the PGLN and ISLN, ipsilateral inspiratory neurons, and contralateral PHR motoneurons.", "contents": "Lateralized phrenic nerve responses to stimulating respiratory afferents in the cat. We stimulated electrically pharyngeal branch of both glossopharyngeal nerves (PGLN), internal branch of superior laryngeal nerves (ISLN), and carotid sinus nerves (CSN) in anesthetized cats. We recorded simultaneously, averaged, and compared bilaterally evoked phrenic nerve (PHR) activity. Our objective was to demonstrate a short-latency evoked response in the PHR contralateral to the stimulus. Low-intensity stimulation of PGLN and ISLN during inspiration evoked a short-latency contralateral excitation with a latency of 5.2 ms +/- 0.2 SE (16 cats) for PGLN, and 3.8 ms +/- 0.1 SE (13 cats) for ISLN. This excitation could follow stimuli delivered at 100 Hz. Stimulation during expiration did not result in a lateralized excitation. The excitation is followed by bilateral inhibition. Neither strychnine nor picrotoxin prevented either the lateralized response or the inhibition, though strychnine diminished a delayed bilateral excitation following PGLN stimulation. This dalayed (latency 18.7 ms +/- 0.7 SE) bilateral excitation corresponds to the sniff reflex. CSN stimulation did not result in lateralized excitation. We suggest that the lateralized evoked response results from a gated paucisynaptic reflex pathway involving the PGLN and ISLN, ipsilateral inspiratory neurons, and contralateral PHR motoneurons."} {"id": "PMID:1275074", "title": "Equilibration of 15N-labeled amino compounds in man.", "content": "Following an overnight fast, either 15N-labeled glycine, or ammonium chloride, or L-aspartate was orally administered to human volunteers in equal hourly aliquots for 8-12 h. In a parallel series of experiments, [15N]glycine and [15N]ammonium chloride were given intravenously at a constant rate for 10-12 h. The amount of 15N given ranged between 2.7 and 27.3 mg/h. Five hundred milligrams of sodium benzoate were given hourly. Venous blood and urine samples were collected serially. The 15N enrichment of the plasma amino nitrogen, urinary ammonia, hippuric acid, and urea were determined. Irrespective of the 15N carrier used or the route of administration, the plasma amino nitrogen, urinary ammonia, and hippuric acid 15N enrichments approached a plateau within 6-10 h. We concluded that human [15N]glycine metabolism was not atypical of amino acids and that mixing, rather than nitrogen interchange reactions, determines the rate in attaining an approximate plateau.", "contents": "Equilibration of 15N-labeled amino compounds in man. Following an overnight fast, either 15N-labeled glycine, or ammonium chloride, or L-aspartate was orally administered to human volunteers in equal hourly aliquots for 8-12 h. In a parallel series of experiments, [15N]glycine and [15N]ammonium chloride were given intravenously at a constant rate for 10-12 h. The amount of 15N given ranged between 2.7 and 27.3 mg/h. Five hundred milligrams of sodium benzoate were given hourly. Venous blood and urine samples were collected serially. The 15N enrichment of the plasma amino nitrogen, urinary ammonia, hippuric acid, and urea were determined. Irrespective of the 15N carrier used or the route of administration, the plasma amino nitrogen, urinary ammonia, and hippuric acid 15N enrichments approached a plateau within 6-10 h. We concluded that human [15N]glycine metabolism was not atypical of amino acids and that mixing, rather than nitrogen interchange reactions, determines the rate in attaining an approximate plateau."} {"id": "PMID:1275075", "title": "Circadian distribution of bile acids in the enterohepatic circulatory system in rats.", "content": "The bile acid pool was first determined in six adult male rats to be 12.8 +/- 0.7 mg/100 g by comparing the total radioactivity of tritiated bile acid drained through the bile fistula and the initial bile acid specific activity. The distribution of bile acids in the enterohepatic circulatory system at various times of the day was then studied in 24 additional rats, each received a single dose of tritiated taurocholate intraperitoneally and was sacrificed 24 h later. The nearly complete recovery of the administered radioactivity from the serum, liver intestinal wall and content, and 24-h feces indicated the confinement of bile acids to the enterohepatic circulation. A remarkable circadian fluctuation of the bile acid content was observed in serum, liver, and intestinal contents. The patterns of such rhythmic change varied from each other in various segments of the intestinal tract but seemed to correlate with the time sequence of movement of bowel content and absorption of bile acids. The circadian rhythm of hepatic synthesis of bile acids but not cholesterol observed by others might be, in part, directly related to the circadian fluctuation of the amount of bile acids in the liver.", "contents": "Circadian distribution of bile acids in the enterohepatic circulatory system in rats. The bile acid pool was first determined in six adult male rats to be 12.8 +/- 0.7 mg/100 g by comparing the total radioactivity of tritiated bile acid drained through the bile fistula and the initial bile acid specific activity. The distribution of bile acids in the enterohepatic circulatory system at various times of the day was then studied in 24 additional rats, each received a single dose of tritiated taurocholate intraperitoneally and was sacrificed 24 h later. The nearly complete recovery of the administered radioactivity from the serum, liver intestinal wall and content, and 24-h feces indicated the confinement of bile acids to the enterohepatic circulation. A remarkable circadian fluctuation of the bile acid content was observed in serum, liver, and intestinal contents. The patterns of such rhythmic change varied from each other in various segments of the intestinal tract but seemed to correlate with the time sequence of movement of bowel content and absorption of bile acids. The circadian rhythm of hepatic synthesis of bile acids but not cholesterol observed by others might be, in part, directly related to the circadian fluctuation of the amount of bile acids in the liver."} {"id": "PMID:1275076", "title": "Endogenous glucagon regulation in genetically hyperlipemic obese rats.", "content": "Glucagon concentration and regulation were examined in the Zucker rat, in which obesity and hyperlipemia are phenotypic expressions of an autosomal recessive gene. Using littermate animals which are phenotypically thin and normolipemic as controls, we observed reduced basal plasma glucagon levels in the obese lipemic rats. In response to fasting, obese lipemic animals inappropriately demonstrated a further reduction in plasma glucagon concentration. In response to pharmacologic glucagon stimulation (arginine), a subnormal rise in plasma glucagon concentration was observed in the obese, lipemic animals. Glucagon suppressibility with exogenous glucose remained intact. The reduced secretion of glucagon may be a consequence of the abnormal elevation in concentration of plasma insulin, free fatty acids, and glucose, which are characteristic of the obese, lipemic animal. A possible role of glucagon deficiency in the evolution or maintenance of the lipemic state is suggested.", "contents": "Endogenous glucagon regulation in genetically hyperlipemic obese rats. Glucagon concentration and regulation were examined in the Zucker rat, in which obesity and hyperlipemia are phenotypic expressions of an autosomal recessive gene. Using littermate animals which are phenotypically thin and normolipemic as controls, we observed reduced basal plasma glucagon levels in the obese lipemic rats. In response to fasting, obese lipemic animals inappropriately demonstrated a further reduction in plasma glucagon concentration. In response to pharmacologic glucagon stimulation (arginine), a subnormal rise in plasma glucagon concentration was observed in the obese, lipemic animals. Glucagon suppressibility with exogenous glucose remained intact. The reduced secretion of glucagon may be a consequence of the abnormal elevation in concentration of plasma insulin, free fatty acids, and glucose, which are characteristic of the obese, lipemic animal. A possible role of glucagon deficiency in the evolution or maintenance of the lipemic state is suggested."} {"id": "PMID:1275077", "title": "Genetic predisposition to stroke in spontaneously hypertensive rats.", "content": "Hypertension and stroke in spontaneously hypertensive rats (SHR) were investigated genetically using stroke-prone SHR (A3), stroke-resistant SHR (C) and their hybrids, hybrid of A3 and C (F1), offspring of F1 X F1 (F2), and those of backcrossing of F1 to the respective parental strains, BC(F1 X A3) and BC(F1 X C). The average blood pressure measured without anesthesia increased in the following order during the experimental period: C less than BC (F1 X C) less than F1 approximately F2 less than BC(F1 X A3) less than A3. The F2 represented a wider spread of variation than the F1, with some of the pressure extending into the range of both parental strains. When the drinking water was replaced with a 1% salt solution, the blood pressure increased and the onset of stroke markedly accelerated in all groups of SHR. Under the hypertensive conditions, the incidence of stroke was associated with A3-gene concentration rather than with the level of blood pressure. Similar but less dramatic effects of salt were observed in another series of hybrid groups derived from A3 and normal Wistar-Kyoto rats. These findings suggest that the genetic factors are of great importance in the development of stroke as well as hypertension in the SHR.", "contents": "Genetic predisposition to stroke in spontaneously hypertensive rats. Hypertension and stroke in spontaneously hypertensive rats (SHR) were investigated genetically using stroke-prone SHR (A3), stroke-resistant SHR (C) and their hybrids, hybrid of A3 and C (F1), offspring of F1 X F1 (F2), and those of backcrossing of F1 to the respective parental strains, BC(F1 X A3) and BC(F1 X C). The average blood pressure measured without anesthesia increased in the following order during the experimental period: C less than BC (F1 X C) less than F1 approximately F2 less than BC(F1 X A3) less than A3. The F2 represented a wider spread of variation than the F1, with some of the pressure extending into the range of both parental strains. When the drinking water was replaced with a 1% salt solution, the blood pressure increased and the onset of stroke markedly accelerated in all groups of SHR. Under the hypertensive conditions, the incidence of stroke was associated with A3-gene concentration rather than with the level of blood pressure. Similar but less dramatic effects of salt were observed in another series of hybrid groups derived from A3 and normal Wistar-Kyoto rats. These findings suggest that the genetic factors are of great importance in the development of stroke as well as hypertension in the SHR."} {"id": "PMID:1275078", "title": "Effects of insulin on cardiac muscle contraction and responsiveness to norepinephrine.", "content": "The effects of insulin (In) on contractile activity of isolated cardiac muscle were studied in right ventricular moderator band (MB) of piglets and papillary muscle (PM) of cats and kittens. The muscles were bathed in modified Krebs solution containing 5.6 mM glucose at 30 degrees C and gassed with 95% O2 and 5% CO2. They were paced at 24 contractions per minute isometrically at Lmax. Addition of In (1 U/ml) to the bath induced a biphasic inotropic response to piglet MB. The initial negative effect was due to the preservative (0.2% phenol) in the regular commercial In solution. Following the transitory depression, both active isometric tension (AT) and maximal rate of tension development increased to a maximum (about 120% of control) within 15 min and then declined slightly toward control. Similar positive responses were observed in both cat and kitten PM, but without the initial negative effect. Maximal responses were not diminished by the absence of glucose in the bath. Increases in AT and dT/dt of both MB and PM in response to NE were significantly attenuated in the presence of In compared with untreated muscle. These findings demonstrate that In elicits a positive inotropic effect on mammalian cardiac muscle and that it impairs the inotropic action of NE.", "contents": "Effects of insulin on cardiac muscle contraction and responsiveness to norepinephrine. The effects of insulin (In) on contractile activity of isolated cardiac muscle were studied in right ventricular moderator band (MB) of piglets and papillary muscle (PM) of cats and kittens. The muscles were bathed in modified Krebs solution containing 5.6 mM glucose at 30 degrees C and gassed with 95% O2 and 5% CO2. They were paced at 24 contractions per minute isometrically at Lmax. Addition of In (1 U/ml) to the bath induced a biphasic inotropic response to piglet MB. The initial negative effect was due to the preservative (0.2% phenol) in the regular commercial In solution. Following the transitory depression, both active isometric tension (AT) and maximal rate of tension development increased to a maximum (about 120% of control) within 15 min and then declined slightly toward control. Similar positive responses were observed in both cat and kitten PM, but without the initial negative effect. Maximal responses were not diminished by the absence of glucose in the bath. Increases in AT and dT/dt of both MB and PM in response to NE were significantly attenuated in the presence of In compared with untreated muscle. These findings demonstrate that In elicits a positive inotropic effect on mammalian cardiac muscle and that it impairs the inotropic action of NE."} {"id": "PMID:1275079", "title": "Eelctrophysiologic and ultrastructural characteristics of the canine tricuspid valve.", "content": "Collagen extending from chordae tendineae sweeps into each tricuspid leaflet in a loose fanlike arrangement merging with the annulus. Each leaflet contains variable amounts of cardiac muscle in continuity with right atrial muscle; valve fibers are sparse, and scattered myofibers and/or bundles of myofibers usually extend only 2-3 mm into the leaflet body. Valve myofibers are structurally identical to working right atrial muscle but are 2-3 mum in diameter compared to 5-7 mum in working muscle. Electrical stimulation of the low right atrial wall often induces propagated activity in the leaflet. Transmembrane recordings obtained from isolated Tyrode superfused leaflets showed low maximum diastolic potential, action potential amplitude, and rate of depolarization; action potentials usually had prominent plateaus. Excitation of discrete regions in tricuspid leaflets did not excite atrial wall, but valve muscle fibers often developed spontaneous diastolic depolarization and automaticity after stretch or exposure to catecholamines Automaticity was suppressed by acetylcholine. Physiological and pathophysiological significance of tricuspid muscle may reside in its participation in valve closure during ventricular contraction and the fact that it is a site of abnormal impulse formation.", "contents": "Eelctrophysiologic and ultrastructural characteristics of the canine tricuspid valve. Collagen extending from chordae tendineae sweeps into each tricuspid leaflet in a loose fanlike arrangement merging with the annulus. Each leaflet contains variable amounts of cardiac muscle in continuity with right atrial muscle; valve fibers are sparse, and scattered myofibers and/or bundles of myofibers usually extend only 2-3 mm into the leaflet body. Valve myofibers are structurally identical to working right atrial muscle but are 2-3 mum in diameter compared to 5-7 mum in working muscle. Electrical stimulation of the low right atrial wall often induces propagated activity in the leaflet. Transmembrane recordings obtained from isolated Tyrode superfused leaflets showed low maximum diastolic potential, action potential amplitude, and rate of depolarization; action potentials usually had prominent plateaus. Excitation of discrete regions in tricuspid leaflets did not excite atrial wall, but valve muscle fibers often developed spontaneous diastolic depolarization and automaticity after stretch or exposure to catecholamines Automaticity was suppressed by acetylcholine. Physiological and pathophysiological significance of tricuspid muscle may reside in its participation in valve closure during ventricular contraction and the fact that it is a site of abnormal impulse formation."} {"id": "PMID:1275080", "title": "Cardiovascular responses to electrocardiogram-coupled stimulation of rabbit aortic nerve.", "content": "Electrical stimulation of the rabbit's aortic nerve during one or more cardiac cycles resulted in a reflex fall in heart rate and mean arterial blood pressure (MAP). The onset of bradycardia and of fall in MAP were independent of the number of beats stimulated. The initial slope of the heart rate and MAP responses increased as the number of beats stimulated increased, reaching a maximum at five beats of stimulation. Bradycardia peaked 8 and 10 beats after the end of one and two cycles of stimulation, respectively, while the peak response occurred at, or prior to, the end of stimulation when 12 or more beats were involved. Onset and recovery of both responses were consistent, and seldom did MAP indicate a return toward control during stimulation. Thus, central nervous system modulation of sympathetic activity to the peripheral vasculature was sustained as long as the aortic nerve input was maintained. However, reflex control of heart rate was more complex, involving simultaneous alteration in both vagal and sympathetic efferent activity.", "contents": "Cardiovascular responses to electrocardiogram-coupled stimulation of rabbit aortic nerve. Electrical stimulation of the rabbit's aortic nerve during one or more cardiac cycles resulted in a reflex fall in heart rate and mean arterial blood pressure (MAP). The onset of bradycardia and of fall in MAP were independent of the number of beats stimulated. The initial slope of the heart rate and MAP responses increased as the number of beats stimulated increased, reaching a maximum at five beats of stimulation. Bradycardia peaked 8 and 10 beats after the end of one and two cycles of stimulation, respectively, while the peak response occurred at, or prior to, the end of stimulation when 12 or more beats were involved. Onset and recovery of both responses were consistent, and seldom did MAP indicate a return toward control during stimulation. Thus, central nervous system modulation of sympathetic activity to the peripheral vasculature was sustained as long as the aortic nerve input was maintained. However, reflex control of heart rate was more complex, involving simultaneous alteration in both vagal and sympathetic efferent activity."} {"id": "PMID:1275081", "title": "De novo synthesis of alanine by the perfused rat hindlimb.", "content": "Due to the disproportionately large production of alanine by muscle, it has been suggested that part of the alanine released by muscle is synthesized de novo by the transamination of glucose-derived pyruvate. This glucose-alanine conversion was quantitated in the isolated rat hindlimb perfused with a solution of bicarbonate buffer containing 2% albumin, 2.4% dextran, 2.5-15.9 mM glucose, 32-34% dog erythrocytes, and 0.05 muCi/ml [14C]glucose. Measurement of labeled alanine production allowed quantitation of de novo alanine synthesis. De novo derived alanine accounted for an average of 33% of the total alanine released by the perfused tissue (perfusate glucose concentration 8.3 mM), concurrently 2.7% of the glucose taken up by the limb was converted to alanine. By increasing the glucose concentration perfusing the muscle, both the rate of glucose uptake and de novo alanine release were increased. Addition of insulin to the perfusate (700 muU/ml) resulted in a significant increase in the rate of glucose uptake and de novo alanine production, but the rate of total alanine release was significantly decreased by the hormone. It was concluded that de novo alanine production accounts for a sizeable portion of the total alanine released by muscle, nevertheless a comparatively small fraction of the glucose carbons are actually transformed to alanine.", "contents": "De novo synthesis of alanine by the perfused rat hindlimb. Due to the disproportionately large production of alanine by muscle, it has been suggested that part of the alanine released by muscle is synthesized de novo by the transamination of glucose-derived pyruvate. This glucose-alanine conversion was quantitated in the isolated rat hindlimb perfused with a solution of bicarbonate buffer containing 2% albumin, 2.4% dextran, 2.5-15.9 mM glucose, 32-34% dog erythrocytes, and 0.05 muCi/ml [14C]glucose. Measurement of labeled alanine production allowed quantitation of de novo alanine synthesis. De novo derived alanine accounted for an average of 33% of the total alanine released by the perfused tissue (perfusate glucose concentration 8.3 mM), concurrently 2.7% of the glucose taken up by the limb was converted to alanine. By increasing the glucose concentration perfusing the muscle, both the rate of glucose uptake and de novo alanine release were increased. Addition of insulin to the perfusate (700 muU/ml) resulted in a significant increase in the rate of glucose uptake and de novo alanine production, but the rate of total alanine release was significantly decreased by the hormone. It was concluded that de novo alanine production accounts for a sizeable portion of the total alanine released by muscle, nevertheless a comparatively small fraction of the glucose carbons are actually transformed to alanine."} {"id": "PMID:1275082", "title": "Ability of exogenous alanine to lower blood beta-hydroxybutyrate during development in rats.", "content": "The intraperitoneal injection of L-alanine into 10- and 21-day-old fed Wistar rats resulted in blood alanine levels of 3-5 mM and in a rapid, significant decrease in the concentration of beta-hydroxybutyrate (betaOHB) in blood. The drop in betaOHB was unrelated to changes in the concentrations of pyruvate, lactate, or glucose. The intraperitoneal injection of glutamate at the same age had no effect on betaOHB values. In 2-day-old pups and in older weaned animals, the injection of alanine had either no effect or increased the levels of betaOHB in blood. The most rapid disappearance of exogenous alanine occurred in 35-day-old and not in 10- and 21-day-old rats. These data suggest that alanine has a depressant effect on the level of circulating betaOHB at a specific stage in the animal's maturation.", "contents": "Ability of exogenous alanine to lower blood beta-hydroxybutyrate during development in rats. The intraperitoneal injection of L-alanine into 10- and 21-day-old fed Wistar rats resulted in blood alanine levels of 3-5 mM and in a rapid, significant decrease in the concentration of beta-hydroxybutyrate (betaOHB) in blood. The drop in betaOHB was unrelated to changes in the concentrations of pyruvate, lactate, or glucose. The intraperitoneal injection of glutamate at the same age had no effect on betaOHB values. In 2-day-old pups and in older weaned animals, the injection of alanine had either no effect or increased the levels of betaOHB in blood. The most rapid disappearance of exogenous alanine occurred in 35-day-old and not in 10- and 21-day-old rats. These data suggest that alanine has a depressant effect on the level of circulating betaOHB at a specific stage in the animal's maturation."} {"id": "PMID:1275083", "title": "Sympathetic innervation of guinea pig uterus and ovary.", "content": "The relative contribution of the ovarian nerves and hypogastric plexus in the innervation of the guinea pig uterus and ovary was assessed. Chronic section of the hypogastric nerve did not reduce norepinephrine (NE) concentration in either organ. Localization of the hypogastric plexus in female guinea pigs was unsuccessful. Crushing the ovarian nerves 1) lowered the NE concentration in the ovary (70%) and in all portions of the uterus (86%), 2) decreased by 80-90% the uterine retention of [3H]NE, and 3) decreased the intensity of fluorescent adrenergic fibers in the uterus. However, the denervated uterus failed to exhibit supersensitivity to NE. In conclusion, sympathetic innervation of the guinea pig uterus and ovary is predominantly via the ovarian nerves, and a minor pathway of innervation may come from hypogastric plexus.", "contents": "Sympathetic innervation of guinea pig uterus and ovary. The relative contribution of the ovarian nerves and hypogastric plexus in the innervation of the guinea pig uterus and ovary was assessed. Chronic section of the hypogastric nerve did not reduce norepinephrine (NE) concentration in either organ. Localization of the hypogastric plexus in female guinea pigs was unsuccessful. Crushing the ovarian nerves 1) lowered the NE concentration in the ovary (70%) and in all portions of the uterus (86%), 2) decreased by 80-90% the uterine retention of [3H]NE, and 3) decreased the intensity of fluorescent adrenergic fibers in the uterus. However, the denervated uterus failed to exhibit supersensitivity to NE. In conclusion, sympathetic innervation of the guinea pig uterus and ovary is predominantly via the ovarian nerves, and a minor pathway of innervation may come from hypogastric plexus."} {"id": "PMID:1275084", "title": "Influence of the oral cavity on insulin release in the rat.", "content": "Blood glucose and insulin levels were measured in undisturbed and free-moving rats. The insulin level rose in the 1st min after the start of food intake; the glucose level began to increase only in the 3rd min if a fluid carbohydrate-rich food was eaten. The insulin release followed a biphasic pattern. If the same quantity of food ingested orally was injected into the stomach in the same time as the animals needed to complete oral ingestion, delayed insulin release could be seen and the second phase of insulin release was exaggerated. The glucose level, which started to rise in the 3rd min, increased much more than during oral ingestion. With respect to insulin release the same phenomena could be observed if carbohydrate-free fluid food was used instead of carbohydrate-rich fluid food. It is argued that the oral cavity plays a major role in the first phase of insulin release, which in its turn seems to be important in the homeostasis of the blood glucose and insulin levels.", "contents": "Influence of the oral cavity on insulin release in the rat. Blood glucose and insulin levels were measured in undisturbed and free-moving rats. The insulin level rose in the 1st min after the start of food intake; the glucose level began to increase only in the 3rd min if a fluid carbohydrate-rich food was eaten. The insulin release followed a biphasic pattern. If the same quantity of food ingested orally was injected into the stomach in the same time as the animals needed to complete oral ingestion, delayed insulin release could be seen and the second phase of insulin release was exaggerated. The glucose level, which started to rise in the 3rd min, increased much more than during oral ingestion. With respect to insulin release the same phenomena could be observed if carbohydrate-free fluid food was used instead of carbohydrate-rich fluid food. It is argued that the oral cavity plays a major role in the first phase of insulin release, which in its turn seems to be important in the homeostasis of the blood glucose and insulin levels."} {"id": "PMID:1275085", "title": "Cerebrospinal fluid [Ca2+] and rectal temperature response during exercise in dogs.", "content": "Rectal temperature (Tre) was measured in five dogs during 1 h of rest and 1 h of moderate treadmill exercise (1.2 m/s up a 12 degree slope), with no infusion and with continuous infusion (40 mul/min) of normocalcic (1.3 mM Ca2+, 151.5 mM Na+) and hypercalcic (2.6 mM Ca2+, 149.6 mM Na+) concentrations of artificial cerebrospinal fluids into the left lateral cerebral ventricle. There was no effect of the normo- or hypercalcic infusions on resting Tre. In comparison with the postexercise Tre level of 39.9 degrees C (deltaTre= +1.4 degrees C) with no infusion, Tre rose to 40.0 degrees C (delta Tre = +1.4 degrees C) with normocalcic infusion (NS); there was a significantly smaller (P less than 0.01) rise in Tre to 39.2 degrees C (delta Tre = +0.8 degrees C) with hypercalcic infusion. The smaller rise in Tre in response to excess Ca2+ in cerebrospinal fluid was not due to plasma fluid or electrolyte shifts. During exercise the mean body weight loss was greater with hypercalcic infusion (-2.7%) compared with normocalcic (-1.0%) and no infusion (-1.4%) values. The results suggest that Ca2+ ions affect the sensitivity of the central thermoreceptor to thermal stimuli and cause an increased heat loss during physical exercise in dogs.", "contents": "Cerebrospinal fluid [Ca2+] and rectal temperature response during exercise in dogs. Rectal temperature (Tre) was measured in five dogs during 1 h of rest and 1 h of moderate treadmill exercise (1.2 m/s up a 12 degree slope), with no infusion and with continuous infusion (40 mul/min) of normocalcic (1.3 mM Ca2+, 151.5 mM Na+) and hypercalcic (2.6 mM Ca2+, 149.6 mM Na+) concentrations of artificial cerebrospinal fluids into the left lateral cerebral ventricle. There was no effect of the normo- or hypercalcic infusions on resting Tre. In comparison with the postexercise Tre level of 39.9 degrees C (deltaTre= +1.4 degrees C) with no infusion, Tre rose to 40.0 degrees C (delta Tre = +1.4 degrees C) with normocalcic infusion (NS); there was a significantly smaller (P less than 0.01) rise in Tre to 39.2 degrees C (delta Tre = +0.8 degrees C) with hypercalcic infusion. The smaller rise in Tre in response to excess Ca2+ in cerebrospinal fluid was not due to plasma fluid or electrolyte shifts. During exercise the mean body weight loss was greater with hypercalcic infusion (-2.7%) compared with normocalcic (-1.0%) and no infusion (-1.4%) values. The results suggest that Ca2+ ions affect the sensitivity of the central thermoreceptor to thermal stimuli and cause an increased heat loss during physical exercise in dogs."} {"id": "PMID:1275086", "title": "Micropuncture evidence of rapid hydrolysis of bradykinin by rat proximal tubule.", "content": "3H-labeled bradykinin ([3H]BKN) and 14C-labeled inulin ([14C]In) were simultaneously microinfused into proximal or distal tubules in Inactin-anesthetized rats, and urinary excretion and tubular transit times were measured. In other experiments higher doses of [3H]BKN were microinfused and intact peptide and its metabolites identified and quantified by two-dimensional peptide mapping. The site of infusion was identified by neoprene injection and microdissection. Urinary recovery of 3H label was 24.1% when proximal tubules were infused and 98.0% when distal tubules were infused. For proximal tubules, 85% of 3H activity recovered from urine consisted of metabolites (81%[3H]Pro and 4% [3H]Arg1-Phe5) and 15% was intact BKN. Urinary recoveries of [3H]BKN and metabolites were unrelated to tubular length. With distal tubules all 3H activity appeared as intact BKN. Excretion curves of simultaneously infused [3H]BKN and [14C]In showed no marked differences in configuration for either proximal or distal or distal tubules. We suggested that removal of [3H]BKN by proximal tubular cells occurs by rapid enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder.", "contents": "Micropuncture evidence of rapid hydrolysis of bradykinin by rat proximal tubule. 3H-labeled bradykinin ([3H]BKN) and 14C-labeled inulin ([14C]In) were simultaneously microinfused into proximal or distal tubules in Inactin-anesthetized rats, and urinary excretion and tubular transit times were measured. In other experiments higher doses of [3H]BKN were microinfused and intact peptide and its metabolites identified and quantified by two-dimensional peptide mapping. The site of infusion was identified by neoprene injection and microdissection. Urinary recovery of 3H label was 24.1% when proximal tubules were infused and 98.0% when distal tubules were infused. For proximal tubules, 85% of 3H activity recovered from urine consisted of metabolites (81%[3H]Pro and 4% [3H]Arg1-Phe5) and 15% was intact BKN. Urinary recoveries of [3H]BKN and metabolites were unrelated to tubular length. With distal tubules all 3H activity appeared as intact BKN. Excretion curves of simultaneously infused [3H]BKN and [14C]In showed no marked differences in configuration for either proximal or distal or distal tubules. We suggested that removal of [3H]BKN by proximal tubular cells occurs by rapid enzymatic cleavage at the luminal surface with reabsorption of most of the products and excretion of the remainder."} {"id": "PMID:1275087", "title": "Oxygen toxicity: augmentation of antioxidant defense mechanisms in rat lung.", "content": "In studies directed at determining the activities of selected enzymes in lung tissue after in vivo exposure to hyperoxia, 70-day-old rats were exposed to 85% or 90% O2 for 1-14 days. After 7 days of exposure to 90% O2 (1atm), superoxide dismutase activities in mitochondrial and cytosolic fractions increased, respectively, to 245 and 145% of control; glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities increased, respectively, to 317, 175, and 413% of control. The levels of reduced glutathione and total nonprotein sulfhydryl compounds were elevated to 195% and 365% of control. Similar changes were observed in rats exposed to 85% O2 for up to 14 days, but to a lesser degree. The changes are interpreted as a reflection of the overall magnitude of oxidant-induced lung injury-reparative processes. The results suggest that hyperoxia induces an increase in lung \"antioxidant\" defense capabilities. This apparent adaptive response may be important in decreasing the susceptibility of lung tissue to continued O2 toxicity.", "contents": "Oxygen toxicity: augmentation of antioxidant defense mechanisms in rat lung. In studies directed at determining the activities of selected enzymes in lung tissue after in vivo exposure to hyperoxia, 70-day-old rats were exposed to 85% or 90% O2 for 1-14 days. After 7 days of exposure to 90% O2 (1atm), superoxide dismutase activities in mitochondrial and cytosolic fractions increased, respectively, to 245 and 145% of control; glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities increased, respectively, to 317, 175, and 413% of control. The levels of reduced glutathione and total nonprotein sulfhydryl compounds were elevated to 195% and 365% of control. Similar changes were observed in rats exposed to 85% O2 for up to 14 days, but to a lesser degree. The changes are interpreted as a reflection of the overall magnitude of oxidant-induced lung injury-reparative processes. The results suggest that hyperoxia induces an increase in lung \"antioxidant\" defense capabilities. This apparent adaptive response may be important in decreasing the susceptibility of lung tissue to continued O2 toxicity."} {"id": "PMID:1275088", "title": "Participation of beta receptors in reflex vasodilatation in the dog.", "content": "The effects of propranolol, given by direct intraarterial injection, on the reflex vasodilatation induced in the atropinized isolated gracilis muscle by rapid intravenous administration of norepinephrine, were studied in dogs. In these studies, both atropine and atropine plus propranolol did not significantly alter the maximum fall in vascular resistance in the perfused gracilis muscle following intravenous norepinephrine; however, if the reflex responses were evaluated as integrated areas of vasodilatation, atropine attenuated the vasodilatation and the administration of propranolol further attenuated the reflex. In fact, the value of the integrated areas of vasodilatation was 52.8 +/- 9 mmHg/min in the basal state, 39 +/- 6 mmHg/min after administration of atropine, and 24 +/- 7 mmHg/min after propranolol, whereas the integrated areas of the systemic hypertension did not show any modification. These results prompt us to conclude that the adrenergic beta receptors participate in the reflex vasodilatation, although the mechanism of their action needs further elucidation.", "contents": "Participation of beta receptors in reflex vasodilatation in the dog. The effects of propranolol, given by direct intraarterial injection, on the reflex vasodilatation induced in the atropinized isolated gracilis muscle by rapid intravenous administration of norepinephrine, were studied in dogs. In these studies, both atropine and atropine plus propranolol did not significantly alter the maximum fall in vascular resistance in the perfused gracilis muscle following intravenous norepinephrine; however, if the reflex responses were evaluated as integrated areas of vasodilatation, atropine attenuated the vasodilatation and the administration of propranolol further attenuated the reflex. In fact, the value of the integrated areas of vasodilatation was 52.8 +/- 9 mmHg/min in the basal state, 39 +/- 6 mmHg/min after administration of atropine, and 24 +/- 7 mmHg/min after propranolol, whereas the integrated areas of the systemic hypertension did not show any modification. These results prompt us to conclude that the adrenergic beta receptors participate in the reflex vasodilatation, although the mechanism of their action needs further elucidation."} {"id": "PMID:1275089", "title": "Influence of blood rheology on intrarenal blood flow distribution.", "content": "This study examined the effects of hematocrit and colloid-induced changes in blood rheology on renal blood flow (RBF) distribution. Blood viscosity, measured by coneplate viscometry, was raised 65% in anesthetized dogs either by increasing hematocrit or giving isoncotic dextran 500. Blood volume was kept constant and arterial pressure was unchanged. An increase in hematocrit caused either no change in RBF or a slight increase at each cortical level (zones 1-4). However, dextran hyperviscosity caused decreases in all four zones, the most pronounced in zone 1 (8.03-5.19 ml min(-1) g(-1)) and the least in zone 4 (1.63-1.46 ml min(-1) g(-1)). These data suggest either that increased hematocrit has less effect on \"apparent viscosity\" of blood within the kidney than does plasma colloid or that increased hematocrit causes renal vasodilatation while colloid hyperviscosity does not cause it. Since GFR remained constant in both types of hyperviscosity, it is possible that GFR is the autoregulated variable and the observed changes in RBF distribution and vascular resistance resulted from the changes in afferent and efferent arteriolar resistance required to preserve GFR.", "contents": "Influence of blood rheology on intrarenal blood flow distribution. This study examined the effects of hematocrit and colloid-induced changes in blood rheology on renal blood flow (RBF) distribution. Blood viscosity, measured by coneplate viscometry, was raised 65% in anesthetized dogs either by increasing hematocrit or giving isoncotic dextran 500. Blood volume was kept constant and arterial pressure was unchanged. An increase in hematocrit caused either no change in RBF or a slight increase at each cortical level (zones 1-4). However, dextran hyperviscosity caused decreases in all four zones, the most pronounced in zone 1 (8.03-5.19 ml min(-1) g(-1)) and the least in zone 4 (1.63-1.46 ml min(-1) g(-1)). These data suggest either that increased hematocrit has less effect on \"apparent viscosity\" of blood within the kidney than does plasma colloid or that increased hematocrit causes renal vasodilatation while colloid hyperviscosity does not cause it. Since GFR remained constant in both types of hyperviscosity, it is possible that GFR is the autoregulated variable and the observed changes in RBF distribution and vascular resistance resulted from the changes in afferent and efferent arteriolar resistance required to preserve GFR."} {"id": "PMID:1275090", "title": "Effect of protein intake on weight gain and plasma amino acid levels in uremic rats.", "content": "Chronically uremic rats weighing approximately 180-200 g and sham-operated controls of similar weight were pair fed diets containing 5, 15 or 23% protein for 10-12 wk. At each level of protein intake, uremic animals gained less weight and had lower protein efficiency ratios than controls. In addition, certain plasma amino acid levels were altered in the uremic animals. These included tyrosine and the tyrosine/phenylalanine ratio, which were decreased, and citrulline, glycine, and the methylhistidines, which were increased. In both uremic and control rats, plasma concentrations of certain amino acids, primarily nonessential ones, varied inversely with protein intake; with the 5% protein diet, the ratio of essential to nonessential amino acids was significantly reduced. These observations indicate that both uremia and reduced protein intake may affect growth and amino acid metabolism in rats with chronic renal failure. The finding that uremic rats utilize protein less efficiently may indicate that marked reductions in protein intake may be particularly hazardous to the nutritional status of the uremic patient.", "contents": "Effect of protein intake on weight gain and plasma amino acid levels in uremic rats. Chronically uremic rats weighing approximately 180-200 g and sham-operated controls of similar weight were pair fed diets containing 5, 15 or 23% protein for 10-12 wk. At each level of protein intake, uremic animals gained less weight and had lower protein efficiency ratios than controls. In addition, certain plasma amino acid levels were altered in the uremic animals. These included tyrosine and the tyrosine/phenylalanine ratio, which were decreased, and citrulline, glycine, and the methylhistidines, which were increased. In both uremic and control rats, plasma concentrations of certain amino acids, primarily nonessential ones, varied inversely with protein intake; with the 5% protein diet, the ratio of essential to nonessential amino acids was significantly reduced. These observations indicate that both uremia and reduced protein intake may affect growth and amino acid metabolism in rats with chronic renal failure. The finding that uremic rats utilize protein less efficiently may indicate that marked reductions in protein intake may be particularly hazardous to the nutritional status of the uremic patient."} {"id": "PMID:1275091", "title": "The \"intoxication state of consciousness\": a model for alcohol and drug abuse.", "content": "The author describes a model of intoxicant use based on altered states of consciousness and reviews his own and others' research on marijuana to illustrate the utility of this model, which is derived from both introspective reports and observed data. The relationship of social behavior and cognitive functioning to the \"intoxication state of consciousness\" is discussed. This state of consciousness may have an adaptive value in engendering and stabilizing social cohesion. Possible treatment implications include cognitive labeling of cues that precipitate episodes of abuse, training for moderated drug use while patients are intoxicated, and providing abusers with altered consciousness through other means, such as meditation.", "contents": "The \"intoxication state of consciousness\": a model for alcohol and drug abuse. The author describes a model of intoxicant use based on altered states of consciousness and reviews his own and others' research on marijuana to illustrate the utility of this model, which is derived from both introspective reports and observed data. The relationship of social behavior and cognitive functioning to the \"intoxication state of consciousness\" is discussed. This state of consciousness may have an adaptive value in engendering and stabilizing social cohesion. Possible treatment implications include cognitive labeling of cues that precipitate episodes of abuse, training for moderated drug use while patients are intoxicated, and providing abusers with altered consciousness through other means, such as meditation."} {"id": "PMID:1275092", "title": "The future of alcohology: craft or science?", "content": "The authors discuss the problems that have resulted from the influx of professionals into the field of alcoholism, which has historically been dominated by paraprofessional workers. The interaction of the professional alcohologist, who operates from a scientific model, with the paraprofessional worker, whose model of treatment has followed craft lines, has created unique problems and tensions. A synergism has been created which has been detrimental rather than complementary. The authors suggest that the future of the alcoholism field will have to be established along craft (paraprofessional) or scientific (professional) lines because the two models cannot profitably co-exist.", "contents": "The future of alcohology: craft or science? The authors discuss the problems that have resulted from the influx of professionals into the field of alcoholism, which has historically been dominated by paraprofessional workers. The interaction of the professional alcohologist, who operates from a scientific model, with the paraprofessional worker, whose model of treatment has followed craft lines, has created unique problems and tensions. A synergism has been created which has been detrimental rather than complementary. The authors suggest that the future of the alcoholism field will have to be established along craft (paraprofessional) or scientific (professional) lines because the two models cannot profitably co-exist."} {"id": "PMID:1275093", "title": "Can psychiatry police itself effectively? The experience of one district branch.", "content": "The growing demand by consumers and government for greater accountability from psychiatry is challenging the traditional system of self-policing by which the profession's standards of ethical conduct are established and maintained. The authors describe the operations of a district branch ethics committee, including types of complaints recieved, investigatory procedures, disposition of cases, and factors limiting the committee's effectiveness. They conclude that in some cases lack of funds, lack of time, and the use of peers to judge alleged misconduct make unbiased and thorough evaluation of complaints difficult. They suggest that psychiatry must take steps to improve public confidence in its ability to police itself so that the power to regulate professional conduct will remain within the profession.", "contents": "Can psychiatry police itself effectively? The experience of one district branch. The growing demand by consumers and government for greater accountability from psychiatry is challenging the traditional system of self-policing by which the profession's standards of ethical conduct are established and maintained. The authors describe the operations of a district branch ethics committee, including types of complaints recieved, investigatory procedures, disposition of cases, and factors limiting the committee's effectiveness. They conclude that in some cases lack of funds, lack of time, and the use of peers to judge alleged misconduct make unbiased and thorough evaluation of complaints difficult. They suggest that psychiatry must take steps to improve public confidence in its ability to police itself so that the power to regulate professional conduct will remain within the profession."} {"id": "PMID:1275094", "title": "Cultural perspectives on the impact of women's changing roles on psychiatry.", "content": "The author examines sex role stereotypes in the United States and their impact on the self-concept of women. She suggests that the fact that women's roles are changing may have a positive impact on general mental health because both men and women will profit from increased flexibility ingender role specifications. She emphasizes the fact that therapists as well as their patients have been socialized into accepting the values and assumptions of our society; there is thus a high probability that not only the presenting complaints but also the treatment goals for women in therapy are culturally determined.", "contents": "Cultural perspectives on the impact of women's changing roles on psychiatry. The author examines sex role stereotypes in the United States and their impact on the self-concept of women. She suggests that the fact that women's roles are changing may have a positive impact on general mental health because both men and women will profit from increased flexibility ingender role specifications. She emphasizes the fact that therapists as well as their patients have been socialized into accepting the values and assumptions of our society; there is thus a high probability that not only the presenting complaints but also the treatment goals for women in therapy are culturally determined."} {"id": "PMID:1275095", "title": "A general systems approach to severe family pathology.", "content": "The author proposes a general systems approach to the examination and understanding of family functioning. Scrutinizing the family as an open system with 1) evolutionary goals and tangible tasks, 2) a need for \"semipermeable\" boundaries, 3) cultural and subcultural communication modes, 4) leadership effectiveness, and 5) the nature and age-appropriateness of the affective bonds will enable clinical judgements about family functioning that indicate general system competencies and defects. Such a framework may also lead to a typology of family process because the major functions of the family as a system (creation, nurturance, enculturation, and guidance of the young into adulthood) can be evaluated regardless of symptoms or diagnoses.", "contents": "A general systems approach to severe family pathology. The author proposes a general systems approach to the examination and understanding of family functioning. Scrutinizing the family as an open system with 1) evolutionary goals and tangible tasks, 2) a need for \"semipermeable\" boundaries, 3) cultural and subcultural communication modes, 4) leadership effectiveness, and 5) the nature and age-appropriateness of the affective bonds will enable clinical judgements about family functioning that indicate general system competencies and defects. Such a framework may also lead to a typology of family process because the major functions of the family as a system (creation, nurturance, enculturation, and guidance of the young into adulthood) can be evaluated regardless of symptoms or diagnoses."} {"id": "PMID:1275096", "title": "The fatal myth of death in the family.", "content": "The author hypothesizes that the observed pathogenic effects on a child of the death of a parent are the result of the family's culture-bound inability to integrate death as a natural part of the process of living. The family tries to deal with death by the avoidance mechanisms of myth and family mystification; it is this process which is pathogenic rather than the experience with death itself. To illustrate his thesis he presents the case history of a man who was fatally affected by the family myth and mystification process.", "contents": "The fatal myth of death in the family. The author hypothesizes that the observed pathogenic effects on a child of the death of a parent are the result of the family's culture-bound inability to integrate death as a natural part of the process of living. The family tries to deal with death by the avoidance mechanisms of myth and family mystification; it is this process which is pathogenic rather than the experience with death itself. To illustrate his thesis he presents the case history of a man who was fatally affected by the family myth and mystification process."} {"id": "PMID:1275097", "title": "A new concept and finding in morbid jealousy.", "content": "The authors describe an unexpected coincidental finding in three couples who sought therapy because the husband was pathologically jealous. In the course of treatment they found that during early adolescence each of these men had witnessed his mother engaged in extramarital sexual activity. The authors discuss the implications of this finding for further understanding of the etiology of the syndrome of pathological jealousy, its transactional dimensions, and possible psychotherapeutic approaches. They also present a typology of morbid jealousy that consists of excessive obsessional-delusional, and ego dysfunctional forms.", "contents": "A new concept and finding in morbid jealousy. The authors describe an unexpected coincidental finding in three couples who sought therapy because the husband was pathologically jealous. In the course of treatment they found that during early adolescence each of these men had witnessed his mother engaged in extramarital sexual activity. The authors discuss the implications of this finding for further understanding of the etiology of the syndrome of pathological jealousy, its transactional dimensions, and possible psychotherapeutic approaches. They also present a typology of morbid jealousy that consists of excessive obsessional-delusional, and ego dysfunctional forms."} {"id": "PMID:1275098", "title": "Treatment for the parents of feminine boys.", "content": "Because extreme boyhood femininity is often a precursor of adult transsexualism, transvestism, and homosexuality, the author recommends early intervention for boys who meet specific behavioral criteria of gender disturbance. It is necessary to involve the parents in such treatment and to deal with the resistances they may have to recognizing and working on the problem as well as problems within the marital relationship that may affect the child's behavior. These boys are remarkably responsive to treatment given between the ages of 5 and 12, becoming more masculine in behavior and more comfortable with their identity as males.", "contents": "Treatment for the parents of feminine boys. Because extreme boyhood femininity is often a precursor of adult transsexualism, transvestism, and homosexuality, the author recommends early intervention for boys who meet specific behavioral criteria of gender disturbance. It is necessary to involve the parents in such treatment and to deal with the resistances they may have to recognizing and working on the problem as well as problems within the marital relationship that may affect the child's behavior. These boys are remarkably responsive to treatment given between the ages of 5 and 12, becoming more masculine in behavior and more comfortable with their identity as males."} {"id": "PMID:1275099", "title": "ECT in the treatment of mania: a controlled study.", "content": "In a chart review study of manic patients, the author found that ECT remarkably improved outcome variables of condition at discharge, duration of hospitalization, and social recovery in comparison with an untreated matched control group. More conclusive evidence would depend on a prospective trial with random assignment of manic patients to ECT, lithium carbonate, and major tranquilizers and blind evaluation of outcome.", "contents": "ECT in the treatment of mania: a controlled study. In a chart review study of manic patients, the author found that ECT remarkably improved outcome variables of condition at discharge, duration of hospitalization, and social recovery in comparison with an untreated matched control group. More conclusive evidence would depend on a prospective trial with random assignment of manic patients to ECT, lithium carbonate, and major tranquilizers and blind evaluation of outcome."} {"id": "PMID:1275100", "title": "Psychiatric illness in homicide victims.", "content": "The authors studied the demographic characteristics and history of psychiatric treatment of 214 homicide victims and 67 suicide victims. Thirty-two (15%) of the homicide victims and 12 (18%) of the suicide victims had a record of psychiatric care; these rates were higher than the treatment rate of the general population. The authors suggest that there may be a connection between the occurrence of homicide and the increased frequency of psychiatric disorders among victims of this crime.", "contents": "Psychiatric illness in homicide victims. The authors studied the demographic characteristics and history of psychiatric treatment of 214 homicide victims and 67 suicide victims. Thirty-two (15%) of the homicide victims and 12 (18%) of the suicide victims had a record of psychiatric care; these rates were higher than the treatment rate of the general population. The authors suggest that there may be a connection between the occurrence of homicide and the increased frequency of psychiatric disorders among victims of this crime."} {"id": "PMID:1275101", "title": "Forensic psychiatry: profiles of two types of sex offenders.", "content": "The authors examined records of 239 individuals charged with sexual offenses and referred by the courts to a forensic service. Defendants charged with rape were typically under 30 with histories of antisocial behavior that included other types of violence. Major mental illness was rare in this group. Child molesters in the sample were of no particular age, usually had no history of violent behavior, and had a low incidence of psychosis. The most common secondary diagnosis in both groups was alcohol or drug abuse.", "contents": "Forensic psychiatry: profiles of two types of sex offenders. The authors examined records of 239 individuals charged with sexual offenses and referred by the courts to a forensic service. Defendants charged with rape were typically under 30 with histories of antisocial behavior that included other types of violence. Major mental illness was rare in this group. Child molesters in the sample were of no particular age, usually had no history of violent behavior, and had a low incidence of psychosis. The most common secondary diagnosis in both groups was alcohol or drug abuse."} {"id": "PMID:1275102", "title": "Peer review of prescribing patterns in a CMHC.", "content": "Monitoring the prescribing patterns of psychiatrists is a challenging and now necessary professional responsibility. The authors describe a peer review and feedback system in a decentralized CMHC, linked to continuing education in psychopharmacology, that made staff psychiatrists familiar with the state of the art and accountable for practice within its guidelines. Data are presented that confirm shifts from polypharmacy toward more appropriate use of psychotropic medications.", "contents": "Peer review of prescribing patterns in a CMHC. Monitoring the prescribing patterns of psychiatrists is a challenging and now necessary professional responsibility. The authors describe a peer review and feedback system in a decentralized CMHC, linked to continuing education in psychopharmacology, that made staff psychiatrists familiar with the state of the art and accountable for practice within its guidelines. Data are presented that confirm shifts from polypharmacy toward more appropriate use of psychotropic medications."} {"id": "PMID:1275103", "title": "Low urinary dopamine and prediction of phenothiazine-induced Parkinsonism: a preliminary report.", "content": "Psychiatric patients who excreted larger amounts of urinary free dopamine before treatment were significantly more likely than patients excreting smaller amounts to develop parkinsonian side effects during moderate-dose trifluoperazine therapy. If this finding is replicated, urinary free dopamine determinations could prove valuable in indicating which patients should receive those antipsychotic drugs least likely to produce extrapyramidal side effects.", "contents": "Low urinary dopamine and prediction of phenothiazine-induced Parkinsonism: a preliminary report. Psychiatric patients who excreted larger amounts of urinary free dopamine before treatment were significantly more likely than patients excreting smaller amounts to develop parkinsonian side effects during moderate-dose trifluoperazine therapy. If this finding is replicated, urinary free dopamine determinations could prove valuable in indicating which patients should receive those antipsychotic drugs least likely to produce extrapyramidal side effects."} {"id": "PMID:1275104", "title": "Sex bias in psychotherapy: a failure to confirm.", "content": "The authors examined the questions of sex-related countertransference and bias in psychotherapy by asking 65 male and 57 female experienced group therapists for clinical reactions to case materials of a bogus outpatient who was designated either male or female. They found that varying the patient's gender produced only small differences in the therapists' responses, and conclude that sex-related countertransference problems may not be as prevalent as had been previously thought.", "contents": "Sex bias in psychotherapy: a failure to confirm. The authors examined the questions of sex-related countertransference and bias in psychotherapy by asking 65 male and 57 female experienced group therapists for clinical reactions to case materials of a bogus outpatient who was designated either male or female. They found that varying the patient's gender produced only small differences in the therapists' responses, and conclude that sex-related countertransference problems may not be as prevalent as had been previously thought."} {"id": "PMID:1275105", "title": "Anticipating the impact of Public Law 93-641 on mental health services.", "content": "Implementation of the new federal law setting up Health Systems Agencies (HSAs) on a regional basis offers many opportunities for participation by psychiatry. On the basis of interviews with mental health service providers, planners, and citizen representatives, the author formulated an inventory of the law's potential impacts, grouped around six general themes. He discusses the positive aspects of each, along with possible problems and hazards.", "contents": "Anticipating the impact of Public Law 93-641 on mental health services. Implementation of the new federal law setting up Health Systems Agencies (HSAs) on a regional basis offers many opportunities for participation by psychiatry. On the basis of interviews with mental health service providers, planners, and citizen representatives, the author formulated an inventory of the law's potential impacts, grouped around six general themes. He discusses the positive aspects of each, along with possible problems and hazards."} {"id": "PMID:1275116", "title": "A framework for prevention: changing health-damaging to health-generating life patterns.", "content": "A set of propositions is offered to provide a frame of reference for proposed strategies to improve healthful behavior by placing personal choice-making in the context of societal option-setting. The health status of populations at a given point in time is seen as a result of customary personal choice-making. These choices in turn are limited by both the perceived and actual options available to individuals, depending on their personal and their community's resources, from which to make choices. Most people, most of the time will make the easiest choices, i.e., will do the things, develop the patterns or life-styles, which seem to cost them less and/or from which they will gain more of what they value in tangible and/or intangible terms.", "contents": "A framework for prevention: changing health-damaging to health-generating life patterns. A set of propositions is offered to provide a frame of reference for proposed strategies to improve healthful behavior by placing personal choice-making in the context of societal option-setting. The health status of populations at a given point in time is seen as a result of customary personal choice-making. These choices in turn are limited by both the perceived and actual options available to individuals, depending on their personal and their community's resources, from which to make choices. Most people, most of the time will make the easiest choices, i.e., will do the things, develop the patterns or life-styles, which seem to cost them less and/or from which they will gain more of what they value in tangible and/or intangible terms."} {"id": "PMID:1275117", "title": "Application of social science theories to family planning health education in the People's Republic of China.", "content": "The transformation of the Chinese society was political and economic by revolution; it was also social and cultural through mass education. Group decisions have been used to induce social change in the Chinese society and applied extensively to the family planning program. The methods which Kurt Lewin developed to change food habits, have been perfected on a grand scale of myriad ways by the Chinese.", "contents": "Application of social science theories to family planning health education in the People's Republic of China. The transformation of the Chinese society was political and economic by revolution; it was also social and cultural through mass education. Group decisions have been used to induce social change in the Chinese society and applied extensively to the family planning program. The methods which Kurt Lewin developed to change food habits, have been perfected on a grand scale of myriad ways by the Chinese."} {"id": "PMID:1275118", "title": "Restraint systems for the prevention of injury to children in automobile accidents.", "content": "Highway accidents are the leading cause of child deaths in the United States from the ages of 1-14 years-6,122 such deaths occurred in 1973. In most instances deaths and permanent injuries occurred with the child as a passenger in an automobile. One approach toward alleviating this problem is the restraint of children in automobiles to reduce the likelihood of injury in a crash.", "contents": "Restraint systems for the prevention of injury to children in automobile accidents. Highway accidents are the leading cause of child deaths in the United States from the ages of 1-14 years-6,122 such deaths occurred in 1973. In most instances deaths and permanent injuries occurred with the child as a passenger in an automobile. One approach toward alleviating this problem is the restraint of children in automobiles to reduce the likelihood of injury in a crash."} {"id": "PMID:1275119", "title": "An evaluation of three techniques improving immunization levels in elementary schools.", "content": "Three techniques for improving immunization levels among school-age children were tested and then compared for most effective use of school nurses' time. Method A involved reviewing school immunization records, specifically inviting immunization-deficient children to a school-based clinic, with some follow-up to achieve good response. Method B involved sending out permission slips for a school-based clinic to all students without additional investment of nursing time. Method C involved a health education program encouraging parents to have their children immunized on their own. Using an average of 38 hours of school nurse time, Method A succeeded significantly better then Method B in immunizing more immunization-deficient children and raising immunization levels , while giving fewer unnecessary immunizations. Method C did not produce significant improvement of immunization levels.", "contents": "An evaluation of three techniques improving immunization levels in elementary schools. Three techniques for improving immunization levels among school-age children were tested and then compared for most effective use of school nurses' time. Method A involved reviewing school immunization records, specifically inviting immunization-deficient children to a school-based clinic, with some follow-up to achieve good response. Method B involved sending out permission slips for a school-based clinic to all students without additional investment of nursing time. Method C involved a health education program encouraging parents to have their children immunized on their own. Using an average of 38 hours of school nurse time, Method A succeeded significantly better then Method B in immunizing more immunization-deficient children and raising immunization levels , while giving fewer unnecessary immunizations. Method C did not produce significant improvement of immunization levels."} {"id": "PMID:1275120", "title": "Skin cancer, melanoma, and sunlight.", "content": "Recent theoretical studies suggest that the earth's ozone layer which filters ultraviolet radiation may be depleted by a fleet of supersonic transports or by continued use of chlorofluoromethanes. It is now generally accepted that short wavelength ultraviolet radiation leads to the development of skin cancer. In this report we demonstrate an approach to estimating the increase in skin cancer incidence associated with increases in skin cancer incidence associated with increases in ultraviolet radiation. The purpose is to demonstrate the logic used and the assumptions that must be made when such estiamtes are made or cited. We emphasize that such estimates should be considered crude until the many assumptions can be investigated.", "contents": "Skin cancer, melanoma, and sunlight. Recent theoretical studies suggest that the earth's ozone layer which filters ultraviolet radiation may be depleted by a fleet of supersonic transports or by continued use of chlorofluoromethanes. It is now generally accepted that short wavelength ultraviolet radiation leads to the development of skin cancer. In this report we demonstrate an approach to estimating the increase in skin cancer incidence associated with increases in skin cancer incidence associated with increases in ultraviolet radiation. The purpose is to demonstrate the logic used and the assumptions that must be made when such estiamtes are made or cited. We emphasize that such estimates should be considered crude until the many assumptions can be investigated."} {"id": "PMID:1275121", "title": "The community hospital as a focus for health planning.", "content": "A community hospital focus for health planning has been developed by a Department of Community Medicine in a \"non-teaching\" voluntary hospital. Results of three years of planning experience have included: descriptions of service area populations and utilizer populations; implementation of neighborhood based health centers with transportation and outreach programs; integration of emergency services with other ambulatory care resources; and proposals for geriatric day-care, ambulatory surgery, and patient education. Working relationships have been developed between the hospital Department and local planning bodies, among them the Comprehensive Health Planning agency, the County Health Services Department, consumer groups, voluntary agencies and a University Health Services Center.", "contents": "The community hospital as a focus for health planning. A community hospital focus for health planning has been developed by a Department of Community Medicine in a \"non-teaching\" voluntary hospital. Results of three years of planning experience have included: descriptions of service area populations and utilizer populations; implementation of neighborhood based health centers with transportation and outreach programs; integration of emergency services with other ambulatory care resources; and proposals for geriatric day-care, ambulatory surgery, and patient education. Working relationships have been developed between the hospital Department and local planning bodies, among them the Comprehensive Health Planning agency, the County Health Services Department, consumer groups, voluntary agencies and a University Health Services Center."} {"id": "PMID:1275122", "title": "Education for adolescent mothers in a hospital setting.", "content": "This paper describes an innovative service program designed to help adolescent mothers become more effective parents. Mother-infant pairs are recruited in the postpartum unit of Cincinnati (Ohio) General Hospital, and weekly classes are held in a pediatric clinic waiting room until infants are approximately six months of age. Medical consultation and/or treatment and education for parenthood in the areas of health, nutrition, and infant stimulation are the foci of the program. The interest and participation of the mothers, the opinion of professionals, tests of maternal knowledge, and measurements of maternal-infant interaction attest to the value and success of this program.", "contents": "Education for adolescent mothers in a hospital setting. This paper describes an innovative service program designed to help adolescent mothers become more effective parents. Mother-infant pairs are recruited in the postpartum unit of Cincinnati (Ohio) General Hospital, and weekly classes are held in a pediatric clinic waiting room until infants are approximately six months of age. Medical consultation and/or treatment and education for parenthood in the areas of health, nutrition, and infant stimulation are the foci of the program. The interest and participation of the mothers, the opinion of professionals, tests of maternal knowledge, and measurements of maternal-infant interaction attest to the value and success of this program."} {"id": "PMID:1275125", "title": "Association between juvenile onset obesity and severe adult obesity in 73, 532 women.", "content": "The association between juvenile obesity and severe adult obesity was examined using a questionnaire completed by 73,532 weight conscious women. Relative obesity as an adult was determined by the ratio Weight/Height. The question, \"Were you considered a fat child?\" determined childhood weight status. Analysis of the data revealed that severely obese women (regardless of age) were 2.4 times more likely than normal weight women to have been fat children. This association was noted for all parity groups. The data also suggests that the risk of a fat child developing severe obesity is substantially greater than that for a non-fat child. Since adult obesity is associated with a number of adult diseases, this study emphasizes the importance of weight control in childhood.", "contents": "Association between juvenile onset obesity and severe adult obesity in 73, 532 women. The association between juvenile obesity and severe adult obesity was examined using a questionnaire completed by 73,532 weight conscious women. Relative obesity as an adult was determined by the ratio Weight/Height. The question, \"Were you considered a fat child?\" determined childhood weight status. Analysis of the data revealed that severely obese women (regardless of age) were 2.4 times more likely than normal weight women to have been fat children. This association was noted for all parity groups. The data also suggests that the risk of a fat child developing severe obesity is substantially greater than that for a non-fat child. Since adult obesity is associated with a number of adult diseases, this study emphasizes the importance of weight control in childhood."} {"id": "PMID:1275127", "title": "Development of a minor illness inventory for children in day care centers.", "content": "A Minor Illness Inventory has been developed for use in systematic investigations of the nature and incidence of minor illness of pre-kindergarten aged children in day care centers. Other researchers are invited to use the authors' Inventory to conduct investigations of some of the important problems associated with health and day care of young children.", "contents": "Development of a minor illness inventory for children in day care centers. A Minor Illness Inventory has been developed for use in systematic investigations of the nature and incidence of minor illness of pre-kindergarten aged children in day care centers. Other researchers are invited to use the authors' Inventory to conduct investigations of some of the important problems associated with health and day care of young children."} {"id": "PMID:1275136", "title": "Vagotomy of the fundic gland area of the stomach without drainage. A definitive treatment for perforated duodenal ulcer.", "content": "Twelve patients in Sweden and thirteen patients in Houston underwent selective proximal vagotomy or parietal cell vagotomy, respectively, for the treatment of perforated duodenal ulcer. A drainage procedure was performed in four of the former and in none of the latter group of patients. There were no operative complications and no operative deaths. Twenty-two of the patients were followed from six months to four years. No patient has recurrent ulcer, dumping, diarrhea, or other significant gastric symptoms during the follow-up period. At the time of their last follow-up, the results were considered excellent or good in all twenty-two patients. The results of this study suggest that SPV or PCV without drainage may be the method of choice for the definitive treatment of all patients with perforated duodenal ulcer who have no obstruction and no contraindications to an operative procedure of greater magnitude than simple closure.", "contents": "Vagotomy of the fundic gland area of the stomach without drainage. A definitive treatment for perforated duodenal ulcer. Twelve patients in Sweden and thirteen patients in Houston underwent selective proximal vagotomy or parietal cell vagotomy, respectively, for the treatment of perforated duodenal ulcer. A drainage procedure was performed in four of the former and in none of the latter group of patients. There were no operative complications and no operative deaths. Twenty-two of the patients were followed from six months to four years. No patient has recurrent ulcer, dumping, diarrhea, or other significant gastric symptoms during the follow-up period. At the time of their last follow-up, the results were considered excellent or good in all twenty-two patients. The results of this study suggest that SPV or PCV without drainage may be the method of choice for the definitive treatment of all patients with perforated duodenal ulcer who have no obstruction and no contraindications to an operative procedure of greater magnitude than simple closure."} {"id": "PMID:1275137", "title": "The urgency of diagnosis and surgical treatment of acute suppurative cholangitis.", "content": "Twenty patients with suppurative cholangitis were seen at the Massachusetts General Hospital over a nine year period. Fifteen patients had acute obstructive suppurative cholangitis due to complete obstruction of the common duct, many with coma, hypotension, and positive blood cultures. Sixty per cent of patients were older than seventy years, and most had a history of biliary tract disease. Although most had jaundice, abdominal pain, and fever, clinical symptoms were variable. The diagnosis of cholangitis was made in only 30 per cent of patients before autopsy or surgery. Eighteen patients had calculi in the common duct, and two had primary fibrosis of the ampulla. Patients explored less than 24 hours after admission or deterioration died less often than those operated on after some delay. Most patients underwent common duct exploration and four had a concomitant sphincterotomy. In one instance, cholecystostomy only was performed and this patient died because of ongoing sepsis. The overall mortality was 40 per cent; of those subjected to operation, 25 per cent died in the hospital. Recovery was dramatic among most survivors, and calculous disease did not recur, except for two patients with retained stones. Prophylactic cholecystectomy is recommended to prevent the occurrence of this subtle and highly dangerous syndrome.", "contents": "The urgency of diagnosis and surgical treatment of acute suppurative cholangitis. Twenty patients with suppurative cholangitis were seen at the Massachusetts General Hospital over a nine year period. Fifteen patients had acute obstructive suppurative cholangitis due to complete obstruction of the common duct, many with coma, hypotension, and positive blood cultures. Sixty per cent of patients were older than seventy years, and most had a history of biliary tract disease. Although most had jaundice, abdominal pain, and fever, clinical symptoms were variable. The diagnosis of cholangitis was made in only 30 per cent of patients before autopsy or surgery. Eighteen patients had calculi in the common duct, and two had primary fibrosis of the ampulla. Patients explored less than 24 hours after admission or deterioration died less often than those operated on after some delay. Most patients underwent common duct exploration and four had a concomitant sphincterotomy. In one instance, cholecystostomy only was performed and this patient died because of ongoing sepsis. The overall mortality was 40 per cent; of those subjected to operation, 25 per cent died in the hospital. Recovery was dramatic among most survivors, and calculous disease did not recur, except for two patients with retained stones. Prophylactic cholecystectomy is recommended to prevent the occurrence of this subtle and highly dangerous syndrome."} {"id": "PMID:1275138", "title": "The continuing challenge of acute and perforated appendicitis.", "content": "A two year review of 216 patients with a preoperative diagnosis of appendicitis is used to help clarify the continuing points of controversy concerning appendicitis. Morbidity of perforated appendicitis by far exceeds that of nonperforated cases. Twenty-nine per cent of patients had perforation with a postoperative complication rate of 33 per cent. Rate of wound infection after perforation was 15 per cent despite antibiotics and delayed wound closure. Pediatric patients in this study did not experience a higher incidence of perforation or complication. A decision tree for management of acute appendicitis is presented.", "contents": "The continuing challenge of acute and perforated appendicitis. A two year review of 216 patients with a preoperative diagnosis of appendicitis is used to help clarify the continuing points of controversy concerning appendicitis. Morbidity of perforated appendicitis by far exceeds that of nonperforated cases. Twenty-nine per cent of patients had perforation with a postoperative complication rate of 33 per cent. Rate of wound infection after perforation was 15 per cent despite antibiotics and delayed wound closure. Pediatric patients in this study did not experience a higher incidence of perforation or complication. A decision tree for management of acute appendicitis is presented."} {"id": "PMID:1275139", "title": "Surgical management of pancreatic trauma.", "content": "Ninety-one patients treated for pancreatic injuries are reviewed. Difficulty of diagnosis, including the surgical management of these injuries and their complications, are discussed in detail. The presence of associated multiple injuries, delay in diagnosis, and lack of sound surgical principles of treatment are directly proportional to the rate of complication and mortality.", "contents": "Surgical management of pancreatic trauma. Ninety-one patients treated for pancreatic injuries are reviewed. Difficulty of diagnosis, including the surgical management of these injuries and their complications, are discussed in detail. The presence of associated multiple injuries, delay in diagnosis, and lack of sound surgical principles of treatment are directly proportional to the rate of complication and mortality."} {"id": "PMID:1275141", "title": "Spontaneous pneumomediastinum.", "content": "Five cases of spontaneous pneumomediastinum are presented. This is a benign condition that requires no specific therapy.", "contents": "Spontaneous pneumomediastinum. Five cases of spontaneous pneumomediastinum are presented. This is a benign condition that requires no specific therapy."} {"id": "PMID:1275143", "title": "Carcinoma of the breast in young women.", "content": "The clinical records of 111 young women with breast carcinoma aged thirty years and younger have been analyzed with respect to the clinical stage of disease when first seen, the histologic status of the regional lymph nodes, and ten year survival. Survival in these young women with mammary carcinoma is equivalent to that of older women when the cancer is in its earliest stage, Stage A, but only if the regional lymph nodes are free from metastatic disease. Once the regional lymph nodes are involved by cancer, the prognosis for these young women is indeed dismal, with less than 20 per cent ten year survival regardless of clinical stage.", "contents": "Carcinoma of the breast in young women. The clinical records of 111 young women with breast carcinoma aged thirty years and younger have been analyzed with respect to the clinical stage of disease when first seen, the histologic status of the regional lymph nodes, and ten year survival. Survival in these young women with mammary carcinoma is equivalent to that of older women when the cancer is in its earliest stage, Stage A, but only if the regional lymph nodes are free from metastatic disease. Once the regional lymph nodes are involved by cancer, the prognosis for these young women is indeed dismal, with less than 20 per cent ten year survival regardless of clinical stage."} {"id": "PMID:1275144", "title": "Breast biopsy: a trial of wound drainage.", "content": "A prospective randomized trial of wound drainage has been performed in a series of ninety-two patients undergoing one hundred breast biopsies. The overall incidence of wound hematoma was 14 per cent but the insertion of a wound drain did not protect against the development of wound hematoma. The wound infection rate was 1 per cent.", "contents": "Breast biopsy: a trial of wound drainage. A prospective randomized trial of wound drainage has been performed in a series of ninety-two patients undergoing one hundred breast biopsies. The overall incidence of wound hematoma was 14 per cent but the insertion of a wound drain did not protect against the development of wound hematoma. The wound infection rate was 1 per cent."} {"id": "PMID:1275145", "title": "The open jejunum: a patch for large duodenal defects.", "content": "A practical solution is presented for the difficult problem posed by a large duodenal defect in a very sick patient. A segment of jejunum opened along its antimesenteric border was applied as a mucosally lined patch, with a favorable result.", "contents": "The open jejunum: a patch for large duodenal defects. A practical solution is presented for the difficult problem posed by a large duodenal defect in a very sick patient. A segment of jejunum opened along its antimesenteric border was applied as a mucosally lined patch, with a favorable result."} {"id": "PMID:1275146", "title": "Lymphangioma of the stomach in a child.", "content": "A case of cystic lymphangioma arising from the stomach wall in a child is reported. This is a rare site of origin for the tumor and its manner of presentation, traumatic rupture, is also unusual. These tumors have not been associated with malignant degeneration. Treatment for these lesions is surgical.", "contents": "Lymphangioma of the stomach in a child. A case of cystic lymphangioma arising from the stomach wall in a child is reported. This is a rare site of origin for the tumor and its manner of presentation, traumatic rupture, is also unusual. These tumors have not been associated with malignant degeneration. Treatment for these lesions is surgical."} {"id": "PMID:1275147", "title": "Serosal patch repair for benign duodenocolic fistula secondary to duodenal diverticulum.", "content": "A case of duodenocolic fistula secondary to a perforating diverticulum of the third portion of the duodenum was successfully managed by primary repair with use of a serosal patch over a difficult duodenal closure. The advantages of the serosal patch technic are discussed in light of other technics used for dealing with duodenal defects and fistulas.", "contents": "Serosal patch repair for benign duodenocolic fistula secondary to duodenal diverticulum. A case of duodenocolic fistula secondary to a perforating diverticulum of the third portion of the duodenum was successfully managed by primary repair with use of a serosal patch over a difficult duodenal closure. The advantages of the serosal patch technic are discussed in light of other technics used for dealing with duodenal defects and fistulas."} {"id": "PMID:1275148", "title": "Papilloma of the gallbladder.", "content": "A case of papilloma of the gallbladder is reported. The gallbladder was associated with cholesterosis but not with stones. The causes of colicky pain in this case are discussed. Papillomas of the gallbladder exhibit no characteristic clinical picture; the symptoms are similar to those of any type of gallbladder disease. Papillomas of the gallbladder may be associated with malignant degeneration. Cholecystectomy is the treatment of choice.", "contents": "Papilloma of the gallbladder. A case of papilloma of the gallbladder is reported. The gallbladder was associated with cholesterosis but not with stones. The causes of colicky pain in this case are discussed. Papillomas of the gallbladder exhibit no characteristic clinical picture; the symptoms are similar to those of any type of gallbladder disease. Papillomas of the gallbladder may be associated with malignant degeneration. Cholecystectomy is the treatment of choice."} {"id": "PMID:1275149", "title": "Intramural gastric abscess.", "content": "Two patients who underwent surgical resection of intramural gastric abscesses are described. Intramural gastric abscesses is a rare problem that simulates more common surgical conditions. The salient features of the symptoms, signs, and findings are reviewed.", "contents": "Intramural gastric abscess. Two patients who underwent surgical resection of intramural gastric abscesses are described. Intramural gastric abscesses is a rare problem that simulates more common surgical conditions. The salient features of the symptoms, signs, and findings are reviewed."} {"id": "PMID:1275150", "title": "Triage for the breast biopsy.", "content": "A plan is advocated for the management of the dominant breast mass with use of local anesthesia in the outpatient setting as the primary diagnostic tool, but with selection of certain patients for immediate general anesthesia biopsy in the \"conventional\" manner. Experience with this plan in 2,492 patients during a period of 114 months shows local anesthesia biopsy to be efficient and accurate. Five year survival for all mastectomy-treated patients whose cancers were diagnosed under local anesthesia is 72 per cent. Use of a triage method for selecting biopsy procedures has resulted in a thirteen-fold decrease in the number of patients subjected to general anesthesia.", "contents": "Triage for the breast biopsy. A plan is advocated for the management of the dominant breast mass with use of local anesthesia in the outpatient setting as the primary diagnostic tool, but with selection of certain patients for immediate general anesthesia biopsy in the \"conventional\" manner. Experience with this plan in 2,492 patients during a period of 114 months shows local anesthesia biopsy to be efficient and accurate. Five year survival for all mastectomy-treated patients whose cancers were diagnosed under local anesthesia is 72 per cent. Use of a triage method for selecting biopsy procedures has resulted in a thirteen-fold decrease in the number of patients subjected to general anesthesia."} {"id": "PMID:1275152", "title": "A stomal appliance for provisional ileostomy in neonates of low weight at birth who require temporary ileostomy.", "content": "In the surgical treatment of infants of low weight at birth for various congenital or acquired intestinal defects, it occasionally becomes necessary to divert intestinal contents by temporary ileostomy. There are no commercially available stomal appliances that are suitable for patients of this size. A rapid and easy method of constructing such an appliance is presented. The appliance protects peristomal skin, reduces nursing skin care time, and provides an easy and efficient method of collecting and measuring stomal affluent.", "contents": "A stomal appliance for provisional ileostomy in neonates of low weight at birth who require temporary ileostomy. In the surgical treatment of infants of low weight at birth for various congenital or acquired intestinal defects, it occasionally becomes necessary to divert intestinal contents by temporary ileostomy. There are no commercially available stomal appliances that are suitable for patients of this size. A rapid and easy method of constructing such an appliance is presented. The appliance protects peristomal skin, reduces nursing skin care time, and provides an easy and efficient method of collecting and measuring stomal affluent."} {"id": "PMID:1275153", "title": "An investigative duodenal tube.", "content": "A triple lumen balloon tube has been designed to study the neutralization and dilutional factors in the pathogenesis of acid-peptic ulceration. This tube is designed to create an in situ duodenal pouch from which duodenal contents may be retrieved before and after stimulation with 0.1 N hydrochloric acid.", "contents": "An investigative duodenal tube. A triple lumen balloon tube has been designed to study the neutralization and dilutional factors in the pathogenesis of acid-peptic ulceration. This tube is designed to create an in situ duodenal pouch from which duodenal contents may be retrieved before and after stimulation with 0.1 N hydrochloric acid."} {"id": "PMID:1275200", "title": "Facial signs of respiratory distress after cardiac surgery. A plea for the clinical approach to mechanical ventilation.", "content": "The face is a rich source of information about the respiratory, cardiovascular and neurological state of the patient. These systems are particularly affected in the adult respiratory distress syndrome (ARDS) after cardiac surgery. It is possible to make firm decisions about mechanical ventilation by scrupulously careful clinical examination, without blood-gas analysis or measurement of respiratory dynamics. The method is also applicable to many other conditions.", "contents": "Facial signs of respiratory distress after cardiac surgery. A plea for the clinical approach to mechanical ventilation. The face is a rich source of information about the respiratory, cardiovascular and neurological state of the patient. These systems are particularly affected in the adult respiratory distress syndrome (ARDS) after cardiac surgery. It is possible to make firm decisions about mechanical ventilation by scrupulously careful clinical examination, without blood-gas analysis or measurement of respiratory dynamics. The method is also applicable to many other conditions."} {"id": "PMID:1275201", "title": "Neonatal flaccidity. Survival after neonatal respiratory failure with extreme flaccidity.", "content": "The birth of a flaccid neonate is described. Oxytocin, diazepam and extradural bupivacaine were used during labour. The baby survived 1 1/2 hours of artificial ventilation and was subsequently healthy. An account is given of the assessment of foetal maturity and the diagnosis of neonatal flaccidity is discussed.", "contents": "Neonatal flaccidity. Survival after neonatal respiratory failure with extreme flaccidity. The birth of a flaccid neonate is described. Oxytocin, diazepam and extradural bupivacaine were used during labour. The baby survived 1 1/2 hours of artificial ventilation and was subsequently healthy. An account is given of the assessment of foetal maturity and the diagnosis of neonatal flaccidity is discussed."} {"id": "PMID:1275202", "title": "Neonatal pneumothorax. A Simple drainage device.", "content": "A simple method of providing under-water-seal drainage using readily available equipment is described. It enables adequate treatment of pneumothorax to be instituted with the minimum delay.", "contents": "Neonatal pneumothorax. A Simple drainage device. A simple method of providing under-water-seal drainage using readily available equipment is described. It enables adequate treatment of pneumothorax to be instituted with the minimum delay."} {"id": "PMID:1275203", "title": "A case of industrial carbon dioxide poisoning.", "content": "A case of poisoning by carbon dioxide from an overhead fire-extinguishing apparatus is reported, and the subsequent rapid reversal of blood-gas and acid-base changes during the recovery phase described. A possible explanation of these changes is discussed.", "contents": "A case of industrial carbon dioxide poisoning. A case of poisoning by carbon dioxide from an overhead fire-extinguishing apparatus is reported, and the subsequent rapid reversal of blood-gas and acid-base changes during the recovery phase described. A possible explanation of these changes is discussed."} {"id": "PMID:1275204", "title": "Centralised system of humidification for respiratory treatment.", "content": "A centralised system of hot water humidifiers for an intensive therapy unit has been described and its performance examined.", "contents": "Centralised system of humidification for respiratory treatment. A centralised system of hot water humidifiers for an intensive therapy unit has been described and its performance examined."} {"id": "PMID:1275205", "title": "A cuffed nasotracheal tube for microlaryngeal surgery.", "content": "A technique of general anaesthetia for microlaryngeal surgery which entails the use of a specially designed long 5 mm cuffed nasotracheal tube is described.", "contents": "A cuffed nasotracheal tube for microlaryngeal surgery. A technique of general anaesthetia for microlaryngeal surgery which entails the use of a specially designed long 5 mm cuffed nasotracheal tube is described."} {"id": "PMID:1275206", "title": "The immediate care of eye injuries.", "content": "The various types of injury which may occur to the eye are described. These may be easily missed altogether, or their extent not realised, unless great care and vigilance is exercised by those who first see the patient. Emphasis has been placed on the immediate care required and the urgency with which the different categories of injury must be referred to a specialist.", "contents": "The immediate care of eye injuries. The various types of injury which may occur to the eye are described. These may be easily missed altogether, or their extent not realised, unless great care and vigilance is exercised by those who first see the patient. Emphasis has been placed on the immediate care required and the urgency with which the different categories of injury must be referred to a specialist."} {"id": "PMID:1275207", "title": "A clinical scoring system for adult respiratory distress. Preliminary report of its use in heart disease.", "content": "A clinical scoring method for assessing adult respiratory distress and the need for mechanical ventilation was matched against simultaneous blood-gas analysis in 27 patients with grave heart disease. The results showed little correlation between the two. Possible reasons for this are discussed.", "contents": "A clinical scoring system for adult respiratory distress. Preliminary report of its use in heart disease. A clinical scoring method for assessing adult respiratory distress and the need for mechanical ventilation was matched against simultaneous blood-gas analysis in 27 patients with grave heart disease. The results showed little correlation between the two. Possible reasons for this are discussed."} {"id": "PMID:1275209", "title": "[Preoperative haemodilution: basis adaption mechanism and limitation of clinical application (author's transl)].", "content": "Basically the adaptational mechanism in acute, normovolaemic dilutional anaemia with dextran-60 is an increased flow rate to organs and tissues due to decreased viscous flow resistance. There is no decrease in systemic oxygen transport and no increase in oxygen extraction ratio unless the hematocrit drops well below 20%. Thus adequate tissue oxygen supply is guaranteed in limited dilution as shown by direct measurements of tissue PO2. The feasibility of a new concept of acute preoperative haemodilution with subsequent autotransfusion of the shed blood is demonstrated in 34 patients. Within the safe limits of clinical dilution in the haematocrit range of 25-20% adequate tissue oxygenation is provided by a rise in cardiac output, whereas heart rate, blood gases and acid base status are essentially unchanged. Autotransfusion during surgery and postoperatively helps to save donor blood, is easy to perform, gives better tissue perfusion at the microcirculatory level and prevents postoperative thromboembolic complications.", "contents": "[Preoperative haemodilution: basis adaption mechanism and limitation of clinical application (author's transl)]. Basically the adaptational mechanism in acute, normovolaemic dilutional anaemia with dextran-60 is an increased flow rate to organs and tissues due to decreased viscous flow resistance. There is no decrease in systemic oxygen transport and no increase in oxygen extraction ratio unless the hematocrit drops well below 20%. Thus adequate tissue oxygen supply is guaranteed in limited dilution as shown by direct measurements of tissue PO2. The feasibility of a new concept of acute preoperative haemodilution with subsequent autotransfusion of the shed blood is demonstrated in 34 patients. Within the safe limits of clinical dilution in the haematocrit range of 25-20% adequate tissue oxygenation is provided by a rise in cardiac output, whereas heart rate, blood gases and acid base status are essentially unchanged. Autotransfusion during surgery and postoperatively helps to save donor blood, is easy to perform, gives better tissue perfusion at the microcirculatory level and prevents postoperative thromboembolic complications."} {"id": "PMID:1275210", "title": "[Haemodynamics, oxygen demand and oxygen uptake of the heart during isovolaemic haemodilution (author's transl)].", "content": "1. In experiments on 5 closed chest dogs an isovolaemic haemodilution with 6% dextran resulted in a drop of haemoglobin content to 6,4g%. Except for a small decrease of arterial pO2 and O2-saturation the body oxygen supply remained undisturbed. -- 2. According to only very small haemodynamic alterations (except compensatory cardiac output increase) myocardial O2-demand increased very little and mainly is caused by moderate augmentation of ventricular wall tension. The decrease of arterial O2 content was fully compensated by an increase of myocardial blood flow. O2 supply to the myocardium was not critically changed. -- 3. In accordance with other investigators it is concluded that in case of coronary insufficiency or increased myocardial O2 demand intentional hemodilution should be avoided. Patients with myocardial insufficiency considered for therapeutic hemodilution should be digitalized preoperatively.", "contents": "[Haemodynamics, oxygen demand and oxygen uptake of the heart during isovolaemic haemodilution (author's transl)]. 1. In experiments on 5 closed chest dogs an isovolaemic haemodilution with 6% dextran resulted in a drop of haemoglobin content to 6,4g%. Except for a small decrease of arterial pO2 and O2-saturation the body oxygen supply remained undisturbed. -- 2. According to only very small haemodynamic alterations (except compensatory cardiac output increase) myocardial O2-demand increased very little and mainly is caused by moderate augmentation of ventricular wall tension. The decrease of arterial O2 content was fully compensated by an increase of myocardial blood flow. O2 supply to the myocardium was not critically changed. -- 3. In accordance with other investigators it is concluded that in case of coronary insufficiency or increased myocardial O2 demand intentional hemodilution should be avoided. Patients with myocardial insufficiency considered for therapeutic hemodilution should be digitalized preoperatively."} {"id": "PMID:1275211", "title": "[Haemodynamics and tolerance to hypoxia of the myocardium under 6%-oxygen ventilation following acute isovolaemic haemodilution in experimental animals (author's transl)].", "content": "1. In experiments on closed chest dogs in a control group and a group of previous isovolaemic haemodiluted dogs a cardiovascular stress was produced by means of reduction of inspiratory O2 content to 6% O2--2. Under haemodilution only small changes of the heart rate, aortic pressure and dp/dtmax occurred, pointing to a decreased sympathoadrenergic response. Augmentation of LVEDP and pulmonary artery pressure is considered to be related to left ventricular insufficiency.--3. According to haemodynamic changes myocardial O2 demand in the control group during hypoxia is increasedby 120% and in contrast remains unchanged after previous haemodilution.--4. Despite the reduced oxygen content under haemodilution severe arterial hypoxemia affects mean survival time of the animals (18.5 min and 21.5 min respectively) only little. However, there is a greater variation from 11 to 26 min in the haemodiluted animals.", "contents": "[Haemodynamics and tolerance to hypoxia of the myocardium under 6%-oxygen ventilation following acute isovolaemic haemodilution in experimental animals (author's transl)]. 1. In experiments on closed chest dogs in a control group and a group of previous isovolaemic haemodiluted dogs a cardiovascular stress was produced by means of reduction of inspiratory O2 content to 6% O2--2. Under haemodilution only small changes of the heart rate, aortic pressure and dp/dtmax occurred, pointing to a decreased sympathoadrenergic response. Augmentation of LVEDP and pulmonary artery pressure is considered to be related to left ventricular insufficiency.--3. According to haemodynamic changes myocardial O2 demand in the control group during hypoxia is increasedby 120% and in contrast remains unchanged after previous haemodilution.--4. Despite the reduced oxygen content under haemodilution severe arterial hypoxemia affects mean survival time of the animals (18.5 min and 21.5 min respectively) only little. However, there is a greater variation from 11 to 26 min in the haemodiluted animals."} {"id": "PMID:1275212", "title": "[Myocardial contractility during limited haemodilution (author's transl)].", "content": "The direct cardiac effects of limited isovolaemic haemodilution by low molecular dextran was investigated in the cat heart-lung preparation. This type of preparation does not allow evaluation of the significance of nervous or humoral influences. All haemodynamic and contractile parameters remain unchanged as does myocardial adaptability to acute changes in pressure or volume load. However, cardiac function curves and the estimation of contractility by means of force-velocity-relations reveal a slight increase of the inotropic state.", "contents": "[Myocardial contractility during limited haemodilution (author's transl)]. The direct cardiac effects of limited isovolaemic haemodilution by low molecular dextran was investigated in the cat heart-lung preparation. This type of preparation does not allow evaluation of the significance of nervous or humoral influences. All haemodynamic and contractile parameters remain unchanged as does myocardial adaptability to acute changes in pressure or volume load. However, cardiac function curves and the estimation of contractility by means of force-velocity-relations reveal a slight increase of the inotropic state."} {"id": "PMID:1275213", "title": "[Hypertonic circulatory response to clinical haemodilution (author's transl)].", "content": "Preoperative haemodilution was performed in 46 patients. By exchange of 1785 ml of patient's blood with plasma substitutes, haematocrit was lowered to 24.8% mean. Cardiac output rose, the other circulatry parameters remained constant on average. 8 patients experienced, however, a circulatory reaction with acute systemic and pulmonary hypertension, peripheral vasoconstriction, and ST-depression in ECG. These cases showed a decrease in oxygen uptake. In further 42 patients haemodilution was limited to haematocrit 27%, and only three weak hypertonic reactions were observed. Therefore we recommend haemodilution to be limited to this hematocrit. Saving homologous blood transfusions is the major goal of haemodilution. In comparable surgical procedures 60-70% of patients without haemodilution are given homologous blood. In our two patient groups with haemodilution blood transfusions were necessary in 15 and 21%, respectively. Thus, haemodilution is a valuable mean of hepatitis prophylaxis by saving homologous blood transfusions. This advantage outweighs the possible risks of circulatory reactions.", "contents": "[Hypertonic circulatory response to clinical haemodilution (author's transl)]. Preoperative haemodilution was performed in 46 patients. By exchange of 1785 ml of patient's blood with plasma substitutes, haematocrit was lowered to 24.8% mean. Cardiac output rose, the other circulatry parameters remained constant on average. 8 patients experienced, however, a circulatory reaction with acute systemic and pulmonary hypertension, peripheral vasoconstriction, and ST-depression in ECG. These cases showed a decrease in oxygen uptake. In further 42 patients haemodilution was limited to haematocrit 27%, and only three weak hypertonic reactions were observed. Therefore we recommend haemodilution to be limited to this hematocrit. Saving homologous blood transfusions is the major goal of haemodilution. In comparable surgical procedures 60-70% of patients without haemodilution are given homologous blood. In our two patient groups with haemodilution blood transfusions were necessary in 15 and 21%, respectively. Thus, haemodilution is a valuable mean of hepatitis prophylaxis by saving homologous blood transfusions. This advantage outweighs the possible risks of circulatory reactions."} {"id": "PMID:1275214", "title": "[Special problems in anaesthesia of haemodiluted patients (author's transl)].", "content": "In a series of 46 patients acute haemodilution was deliberately performed to test the validity of experimental data in clinical practice. Several metabolic and haemodynamic parameters as well as continuous registration of ECG were followed. The withdrawn blood has been exchanged by Dextran 60/PPL in equal quantities resp. by 5% human albumin. Using Dextran 60/PPL a light degree of hypervolemia (700 ml) was applied. Results confirmed that haemodilution is practicable in patients in principe. Exchange of blood by human albumin was followed by less severe side effect of haemodilution than was exchange by Dextran 60/PPL. in mild hypervolaemia. The course of haemodiluted and non haemodiluted patients during comparable surgical procedures (gastrointestinal operations) has been analysed: although measured parameters did not differ significantly between both series--except of Hb and Hk--side effects of the cardiovascular type were more frequently observed in the hemodilutiongroup. Provided there is knowledge of the dangers and side effects and special care (control monitoring) of the patients by the anesthesiologist, acute hemodilution is further recommended.", "contents": "[Special problems in anaesthesia of haemodiluted patients (author's transl)]. In a series of 46 patients acute haemodilution was deliberately performed to test the validity of experimental data in clinical practice. Several metabolic and haemodynamic parameters as well as continuous registration of ECG were followed. The withdrawn blood has been exchanged by Dextran 60/PPL in equal quantities resp. by 5% human albumin. Using Dextran 60/PPL a light degree of hypervolemia (700 ml) was applied. Results confirmed that haemodilution is practicable in patients in principe. Exchange of blood by human albumin was followed by less severe side effect of haemodilution than was exchange by Dextran 60/PPL. in mild hypervolaemia. The course of haemodiluted and non haemodiluted patients during comparable surgical procedures (gastrointestinal operations) has been analysed: although measured parameters did not differ significantly between both series--except of Hb and Hk--side effects of the cardiovascular type were more frequently observed in the hemodilutiongroup. Provided there is knowledge of the dangers and side effects and special care (control monitoring) of the patients by the anesthesiologist, acute hemodilution is further recommended."} {"id": "PMID:1275215", "title": "[Clinical experiences with induced preoperative haemodilution in vascular surgery (author's transl)].", "content": "A procedure of haemodilution modified for the particular requirements of vascular surgery has been used on 90 hospital patients. 61% of the operations have been performed without using homologous blood. The method applied being clinically well tolerable, it the object of this study to find to what extent a measurable reduction of the loss of blood during the operation with consequently a reduction of the amount of homologous blood administered can be attained. If the tolerable loss of blood is estimated to be 600 ml, in 22% of the cases operated on the administration of homologous blood has been avoided. The improvement in rheology by the infusion of low molecular weight dextran is considered an additional advantage in the special field of vascular surgery.", "contents": "[Clinical experiences with induced preoperative haemodilution in vascular surgery (author's transl)]. A procedure of haemodilution modified for the particular requirements of vascular surgery has been used on 90 hospital patients. 61% of the operations have been performed without using homologous blood. The method applied being clinically well tolerable, it the object of this study to find to what extent a measurable reduction of the loss of blood during the operation with consequently a reduction of the amount of homologous blood administered can be attained. If the tolerable loss of blood is estimated to be 600 ml, in 22% of the cases operated on the administration of homologous blood has been avoided. The improvement in rheology by the infusion of low molecular weight dextran is considered an additional advantage in the special field of vascular surgery."} {"id": "PMID:1275216", "title": "[Haemodilution in neurosurgical operations (author's transl)].", "content": "The subject of this paper is an investigation of the usefulness of haemodilution in neurosurgical operations. The studies were carried out on 30 patients undergoing operations for intracranial aneurysms (17 patients) or intracranial tumours (13 patients). The control group consisted of 50 patients undergoing operations for intracranial tumours (25 patients) or cerebral aneurysms (25 patients). It was found that during haemodilution cerebral oedema did not occur during the operation, while in the control group cerebral oedema was observed in 28% operations of the cerebral aneurysms and in 56%-- of the cerebral tumors. The amount of transfused blood in the group with intracranial tumors was diminished by ca 150 ml and in the group with cerebral aneurysms blood transfusion was not necessary at all (in the control group the average transfusion was 310 ml). Described method in correlation with the controlled hypotension should be more widely used in the neurosurgical operations.", "contents": "[Haemodilution in neurosurgical operations (author's transl)]. The subject of this paper is an investigation of the usefulness of haemodilution in neurosurgical operations. The studies were carried out on 30 patients undergoing operations for intracranial aneurysms (17 patients) or intracranial tumours (13 patients). The control group consisted of 50 patients undergoing operations for intracranial tumours (25 patients) or cerebral aneurysms (25 patients). It was found that during haemodilution cerebral oedema did not occur during the operation, while in the control group cerebral oedema was observed in 28% operations of the cerebral aneurysms and in 56%-- of the cerebral tumors. The amount of transfused blood in the group with intracranial tumors was diminished by ca 150 ml and in the group with cerebral aneurysms blood transfusion was not necessary at all (in the control group the average transfusion was 310 ml). Described method in correlation with the controlled hypotension should be more widely used in the neurosurgical operations."} {"id": "PMID:1275217", "title": "[Experiences in performing preoperative isovolaemic haemodilution in a medium-sized hospital (author's transl)].", "content": "The paper discusses the question whether preoperative isovolaemic haemodilution is indicated in relation to operations in a medium-sized hospital. Haemodilution with Dextran 40 and Dextran 60 is performed the day before operation and both methods are compared. It seems, that preoperative haemodilution with Dextran 60 may be recommended in certain circumstances.", "contents": "[Experiences in performing preoperative isovolaemic haemodilution in a medium-sized hospital (author's transl)]. The paper discusses the question whether preoperative isovolaemic haemodilution is indicated in relation to operations in a medium-sized hospital. Haemodilution with Dextran 40 and Dextran 60 is performed the day before operation and both methods are compared. It seems, that preoperative haemodilution with Dextran 60 may be recommended in certain circumstances."} {"id": "PMID:1275218", "title": "[Possibilities and limit of preoperative isovolaemic haemodilution in a district hospital (author's transl)].", "content": "Methods and techniques of preoperative isovolaemic haemodilution in a district hospital are described. In 15 of 19 patients the retransfusion of autologous blood was adequate to compensate the intraoperative loss of blood after isovolaemic haemodilution. Fatalities of serious incidents were not observed. The performance of isovolaemic haemodilution presupposes the necessity of sufficient staff and technical equipment.", "contents": "[Possibilities and limit of preoperative isovolaemic haemodilution in a district hospital (author's transl)]. Methods and techniques of preoperative isovolaemic haemodilution in a district hospital are described. In 15 of 19 patients the retransfusion of autologous blood was adequate to compensate the intraoperative loss of blood after isovolaemic haemodilution. Fatalities of serious incidents were not observed. The performance of isovolaemic haemodilution presupposes the necessity of sufficient staff and technical equipment."} {"id": "PMID:1275219", "title": "[Early influence of acute preoperative haemodilution with human albumin and ringer's lactate on coagulation (author's transl)].", "content": "Acute haemodilution was performed in 10 patients scheduled mainly for vascular surgery. Before induction to anaesthesia 910 +/- 29.1 ml whole blood was taken and simultaneously replaced as follows: 50% of that amount with 3,6% albumin solution, another 50% X 3 with lactated Ringer solution. The haematocrit was thus lowered from 39.8 +/- 1.71 to 28.4 +/- 1.7 vol%. Extensive clotting studies were performed to investigate the early influence of haemodilution on the clotting mechanisms in the time span between the end of blood collection and the point of surgical anaesthesia. The group of patients with normal clotting studies prior to haemodilution has shown a slight and short-lasting hypercoagulability. This has been proven by a shortening of r and k in TEG, by a shortening of non-activated Partial Thromboplastin Time (means activation of the XII and XI factor) and also, by the presence of an activated factor Xa and by an increase of maximum platelet aggregation and of platelet factor 3 availability. This mechanism of clotting activation is similar to the one observed after marked blood loss. It was assumed that this minor, early and short-lasting hypercoagulability has no further influence on the well known usual intra- and post-operative changes in clotting mechanisms (intra-op lowered, post-op enhanced coagulability). In contrast to the patients with normal clotting, a clotting defect due to preexisting liver-cell damage becomes worse during the haemodilution, which method in the presence of hepatic insufficiency therefore is contraindicted. A few additional data on input-output, serum and urine electrolytes and on 2,3 DPG have been gathered during our study. They indicate a positive fluid balance and the necessity for a close watch of electrolytes. The possible trend of 2.3 DPG elevation which has also been found might reflect a compensatory mechanism increasing oxygen transport capacity of haemoglobin if the above described method of haemodilution is used.", "contents": "[Early influence of acute preoperative haemodilution with human albumin and ringer's lactate on coagulation (author's transl)]. Acute haemodilution was performed in 10 patients scheduled mainly for vascular surgery. Before induction to anaesthesia 910 +/- 29.1 ml whole blood was taken and simultaneously replaced as follows: 50% of that amount with 3,6% albumin solution, another 50% X 3 with lactated Ringer solution. The haematocrit was thus lowered from 39.8 +/- 1.71 to 28.4 +/- 1.7 vol%. Extensive clotting studies were performed to investigate the early influence of haemodilution on the clotting mechanisms in the time span between the end of blood collection and the point of surgical anaesthesia. The group of patients with normal clotting studies prior to haemodilution has shown a slight and short-lasting hypercoagulability. This has been proven by a shortening of r and k in TEG, by a shortening of non-activated Partial Thromboplastin Time (means activation of the XII and XI factor) and also, by the presence of an activated factor Xa and by an increase of maximum platelet aggregation and of platelet factor 3 availability. This mechanism of clotting activation is similar to the one observed after marked blood loss. It was assumed that this minor, early and short-lasting hypercoagulability has no further influence on the well known usual intra- and post-operative changes in clotting mechanisms (intra-op lowered, post-op enhanced coagulability). In contrast to the patients with normal clotting, a clotting defect due to preexisting liver-cell damage becomes worse during the haemodilution, which method in the presence of hepatic insufficiency therefore is contraindicted. A few additional data on input-output, serum and urine electrolytes and on 2,3 DPG have been gathered during our study. They indicate a positive fluid balance and the necessity for a close watch of electrolytes. The possible trend of 2.3 DPG elevation which has also been found might reflect a compensatory mechanism increasing oxygen transport capacity of haemoglobin if the above described method of haemodilution is used."} {"id": "PMID:1275220", "title": "[What gains are actually attained through acute preoperative haemodilution? (author's transl)].", "content": "The effect of haemodilution defined as a gain in volume of bodyowned erythrocytes amounts only 116 ml. This calculation assumes an acute haemodilution with four banket-blood and a blood-loss of 2,000 ml during the operation. In addition to this method--if considered useful at all--a conserve of bodyowned blood, to be taken ca. one week before the operation, is recommended.", "contents": "[What gains are actually attained through acute preoperative haemodilution? (author's transl)]. The effect of haemodilution defined as a gain in volume of bodyowned erythrocytes amounts only 116 ml. This calculation assumes an acute haemodilution with four banket-blood and a blood-loss of 2,000 ml during the operation. In addition to this method--if considered useful at all--a conserve of bodyowned blood, to be taken ca. one week before the operation, is recommended."} {"id": "PMID:1275221", "title": "[Why are calculated \"in-vitro\" effects of preoperative haemodilution in variance with respective clinical findings? (author's transl)].", "content": "Whereas theoretical calculations on the effect of hemodilution show a low gain of erythrocytes, the blood saving effect under clinical conditions is considerably higher. Withdrawal of 1,975 ml blood for haemodilution and an intraoperative blood loss of 2,480 ml resulted in saving of 298 ml of red cells or 850 ml of whole blood (haematocrit 35%). This amount of blood saved seems not very much, but it made the transfusion of donor blood unnecessary in cases when otherwise 1--2 units of homologous blood would have been given. Withdrawal of autologous blood 8--10 days prior to an operation planned to be performed under haemodilution is possible, in our experience however, not practical in clinical routine, because of the considerable logistical problems involved.", "contents": "[Why are calculated \"in-vitro\" effects of preoperative haemodilution in variance with respective clinical findings? (author's transl)]. Whereas theoretical calculations on the effect of hemodilution show a low gain of erythrocytes, the blood saving effect under clinical conditions is considerably higher. Withdrawal of 1,975 ml blood for haemodilution and an intraoperative blood loss of 2,480 ml resulted in saving of 298 ml of red cells or 850 ml of whole blood (haematocrit 35%). This amount of blood saved seems not very much, but it made the transfusion of donor blood unnecessary in cases when otherwise 1--2 units of homologous blood would have been given. Withdrawal of autologous blood 8--10 days prior to an operation planned to be performed under haemodilution is possible, in our experience however, not practical in clinical routine, because of the considerable logistical problems involved."} {"id": "PMID:1275291", "title": "Ultrastructural changes in satellite cells after denervation and reinnervation of skeletal muscles.", "content": "Changes taking place in the satellite cells after denervation and reinnervation of skeletal muscles are studied. A certain degree of similarity and synchrony of the changes occurring in these cells and in the muscle fibers is established during the degenerative and regenerative processes. Formation of new satellite cells and fusion of the same with muscle cells is not observed. These findings are explained by the fact that postdenervation changes in the skeletal muscles are not so heavy as in their direct lesion when, according to literature data, the satellite cells participate directly in the reparative process.", "contents": "Ultrastructural changes in satellite cells after denervation and reinnervation of skeletal muscles. Changes taking place in the satellite cells after denervation and reinnervation of skeletal muscles are studied. A certain degree of similarity and synchrony of the changes occurring in these cells and in the muscle fibers is established during the degenerative and regenerative processes. Formation of new satellite cells and fusion of the same with muscle cells is not observed. These findings are explained by the fact that postdenervation changes in the skeletal muscles are not so heavy as in their direct lesion when, according to literature data, the satellite cells participate directly in the reparative process."} {"id": "PMID:1275292", "title": "[The influence of the N-mustard derivative \"cytostasan\" on pregnancy and fetal development in the rat].", "content": "This presentation describes the action of Cytostasan, a nitrogen mustard compound of benzimidazole, on reproduction and embryonic development of Wistar rats. Single doses from 20 through 100 mg/kg body weight were given intraperitoneally on the 4th, 7th, 9th, 11th or 13th day post coitum. All test animals were sacrificed on the 20th day of pregnancy. The following parameters served as a base for evaluation: the means of implantation rates, resorption rates, fetal body weights and the number of dead and living fetuses. Malformations were detected by outer inspection for gross anomalies, by means of the razor blade technique for malformations of organs and by alizarin preparations for detecting anomalies of the osseuos skeleton. All results were compared with those of an untreated control group and evaluated by statistical means. Cytostasan exerts embryotoxic and teratogenic effects in appropriate dosage. Notwithstanding the fact of giving high doses (1/2 LD 50) there is no loss of blastocysts before implantation: the number of implantation sites equals that of the control group. The resorption rate increases at all examined days of development after application of 40 mg/kg, but 20 mg/kg exert effects only on days 4, 7, and 11 p. c. There is no action on the number of living fetuses after injection of 20 mg Cytostasan/kg body weight. After application of 40 mg/kg the number of living fetuses decreases especially on the 7th, 9th, and 13th day p. c. There is a dose-dependent stunting: the fetal body weight is not reduced after a dosage of 20 mg/kg, but 40 mg/kg cause a considerable loss of weight during embryogenesis (days 9, 11, 13). It is impossible to induce stunting during blastogenesis (days 4 and 7). The observed patterns of malformation are relatively uniform: kinked tails, omphaloceles, hydronephroses, hydrocephali. Skeletal defects are absent. The results received are compared with other findings on aklylating antitumour drugs.", "contents": "[The influence of the N-mustard derivative \"cytostasan\" on pregnancy and fetal development in the rat]. This presentation describes the action of Cytostasan, a nitrogen mustard compound of benzimidazole, on reproduction and embryonic development of Wistar rats. Single doses from 20 through 100 mg/kg body weight were given intraperitoneally on the 4th, 7th, 9th, 11th or 13th day post coitum. All test animals were sacrificed on the 20th day of pregnancy. The following parameters served as a base for evaluation: the means of implantation rates, resorption rates, fetal body weights and the number of dead and living fetuses. Malformations were detected by outer inspection for gross anomalies, by means of the razor blade technique for malformations of organs and by alizarin preparations for detecting anomalies of the osseuos skeleton. All results were compared with those of an untreated control group and evaluated by statistical means. Cytostasan exerts embryotoxic and teratogenic effects in appropriate dosage. Notwithstanding the fact of giving high doses (1/2 LD 50) there is no loss of blastocysts before implantation: the number of implantation sites equals that of the control group. The resorption rate increases at all examined days of development after application of 40 mg/kg, but 20 mg/kg exert effects only on days 4, 7, and 11 p. c. There is no action on the number of living fetuses after injection of 20 mg Cytostasan/kg body weight. After application of 40 mg/kg the number of living fetuses decreases especially on the 7th, 9th, and 13th day p. c. There is a dose-dependent stunting: the fetal body weight is not reduced after a dosage of 20 mg/kg, but 40 mg/kg cause a considerable loss of weight during embryogenesis (days 9, 11, 13). It is impossible to induce stunting during blastogenesis (days 4 and 7). The observed patterns of malformation are relatively uniform: kinked tails, omphaloceles, hydronephroses, hydrocephali. Skeletal defects are absent. The results received are compared with other findings on aklylating antitumour drugs."} {"id": "PMID:1275293", "title": "[The influencing of blastogenesis and embryogenesis in rats through aminoacetonitrile].", "content": "The study was designed to determine the influence of the lathyrogenic substance aminoacetonitrile on blastogenesis and embryogenesis of the Wistar rat. 91 female Wistar rats, weighing from 190 through 380 g, received a single injection of 300 mg aminoacetonitrile (AAN)/kg body weight. Substance was given intraperitoneally on days 5, 7, 9, 11 or 13 of pregnancy. The detection of sperms in the vaginal smears was counted as day 1 post coitum. Animals were sacrificed on day 21 of pregnancy. The following parameters served as a base of interpretation: fetal body weight, numbers of implantations, resorptions, dead and living fetuses. Malformations were detected by outer inspection for gross anomalies, by the razor blade technique for internal malformations, and by skeletal preparations. All results were evaluated by statistical means. AAN influences pregnancy and fetal development. The rates of fetal resorptions are enhanced after application of AAN beyond the 7th day p. c. The maximum of fetal death is reached on day 11 p. c. There is no influence on the mean implantation number. With the exception of the 5th day of development AAN reduces the number of living fetuses. After application of AAN on day 13 p.c. the mean body weight decreases significantly. All over the investigated range malformations can be observed. Abnormalities of internal organs are frequent: Hydrocephalus, hydronephrosis, situs inversus. Malformations of the skeletal system are only observable on days 5, 7 and 9: sternal fissure, supernumerary ribs, destruction of the lumbar spine. AAN does not induce gross anomalies of the fetus.", "contents": "[The influencing of blastogenesis and embryogenesis in rats through aminoacetonitrile]. The study was designed to determine the influence of the lathyrogenic substance aminoacetonitrile on blastogenesis and embryogenesis of the Wistar rat. 91 female Wistar rats, weighing from 190 through 380 g, received a single injection of 300 mg aminoacetonitrile (AAN)/kg body weight. Substance was given intraperitoneally on days 5, 7, 9, 11 or 13 of pregnancy. The detection of sperms in the vaginal smears was counted as day 1 post coitum. Animals were sacrificed on day 21 of pregnancy. The following parameters served as a base of interpretation: fetal body weight, numbers of implantations, resorptions, dead and living fetuses. Malformations were detected by outer inspection for gross anomalies, by the razor blade technique for internal malformations, and by skeletal preparations. All results were evaluated by statistical means. AAN influences pregnancy and fetal development. The rates of fetal resorptions are enhanced after application of AAN beyond the 7th day p. c. The maximum of fetal death is reached on day 11 p. c. There is no influence on the mean implantation number. With the exception of the 5th day of development AAN reduces the number of living fetuses. After application of AAN on day 13 p.c. the mean body weight decreases significantly. All over the investigated range malformations can be observed. Abnormalities of internal organs are frequent: Hydrocephalus, hydronephrosis, situs inversus. Malformations of the skeletal system are only observable on days 5, 7 and 9: sternal fissure, supernumerary ribs, destruction of the lumbar spine. AAN does not induce gross anomalies of the fetus."} {"id": "PMID:1275294", "title": "Further observations on the epicardial lymph circulation.", "content": "In the lymphatic vessels in the heart of the pig are structures that influence and determine the direction of the flow of the lymph. These flow-directing structures include simple invaginations of the vessel walls, single-valvulate valves, and double-valvulate valves. The anatomy, frequency, and placement of these structures vary according to differences in the forces maintaining lymph flow. The histology and fine structure of these valves is similar to those of the mesenterium.", "contents": "Further observations on the epicardial lymph circulation. In the lymphatic vessels in the heart of the pig are structures that influence and determine the direction of the flow of the lymph. These flow-directing structures include simple invaginations of the vessel walls, single-valvulate valves, and double-valvulate valves. The anatomy, frequency, and placement of these structures vary according to differences in the forces maintaining lymph flow. The histology and fine structure of these valves is similar to those of the mesenterium."} {"id": "PMID:1275295", "title": "Gross, histomorphological and histochemical changes in the thyroid gland of goat with age. III. Occurrence of thymic tissue.", "content": "The observations on the thyroid glands from 26 goats aged between 20 days and about 5 years revealed the presence of thymic tissue embedded within or in close vicinity of thyroid in 26.9% of the animals, generally occurring in association with parathyroid tissue (23.08%) and only occasionaly (3.84%) alone. Different forms of the thymic tissue associated to thyroid and variations in their histomorphology and PAS reaction in relation to age has been observed and discussed.", "contents": "Gross, histomorphological and histochemical changes in the thyroid gland of goat with age. III. Occurrence of thymic tissue. The observations on the thyroid glands from 26 goats aged between 20 days and about 5 years revealed the presence of thymic tissue embedded within or in close vicinity of thyroid in 26.9% of the animals, generally occurring in association with parathyroid tissue (23.08%) and only occasionaly (3.84%) alone. Different forms of the thymic tissue associated to thyroid and variations in their histomorphology and PAS reaction in relation to age has been observed and discussed."} {"id": "PMID:1275296", "title": "[Ultrastructural changes in cells of the inner enamel epithelium, stratum intermedium and reticulum stellatum in the enamel organ of the upper incisor of the Wistar rat at different phases of amelogenesis].", "content": "An electronmicroscopical study of the enamel organ of the upper incisors germs of Wistar rats was performed to analyse the ultrastructural features of the cells of the inner epithelium, the intermediate layer and the stellate reticulum, during preimary, young, transitional and mineralized enamel phases of amelogenesis. So, it was observed that the mitochondria in the ameloblasts are ovoid before the beginning of the enamel matrix formation and in the primary and young enamel phases. However, in the transitional and mineralized phases, these organelles are long and tortuous and some are characterized by a compact structure. In the cells of intermediate layer and stellate reticulum, the mitochondria are ovoid until the beginning of the mineralized phase. At the ending of this phase, these organelles are very long and present irregular form; many of them show also a compact structure. The \"zonula adhaerens\" could be observed only in the ameloblasts of the primary and young enamel phase. The cytoplasm of ameloblasts, during primary and young enamel phases is characterized by an abundance of free ribosomes and a branular endoplasmic reticulum; but during transitional and mineralized enamel phases, the cytoplasm of these cells shows little granular endoplasmic reticulum and free ribosomes, but ehe agranular endoplasmic reticulum is present. The granular endoplasmic reticulum and free ribosomes are abundant in the cells of the intermediate layer and stellate reticulum at the ending of the young enamel phase, in the transitional enamel phase and in the beginning of the minieralized phase. During different phases of amelogenesis, in the three above referred layers of the enamel organ, were also studied the features of the Golgi apparatus the presence and topographic distribution of the pigment granules, as well as the lysosomes, desmosomes and the tonophibriles.", "contents": "[Ultrastructural changes in cells of the inner enamel epithelium, stratum intermedium and reticulum stellatum in the enamel organ of the upper incisor of the Wistar rat at different phases of amelogenesis]. An electronmicroscopical study of the enamel organ of the upper incisors germs of Wistar rats was performed to analyse the ultrastructural features of the cells of the inner epithelium, the intermediate layer and the stellate reticulum, during preimary, young, transitional and mineralized enamel phases of amelogenesis. So, it was observed that the mitochondria in the ameloblasts are ovoid before the beginning of the enamel matrix formation and in the primary and young enamel phases. However, in the transitional and mineralized phases, these organelles are long and tortuous and some are characterized by a compact structure. In the cells of intermediate layer and stellate reticulum, the mitochondria are ovoid until the beginning of the mineralized phase. At the ending of this phase, these organelles are very long and present irregular form; many of them show also a compact structure. The \"zonula adhaerens\" could be observed only in the ameloblasts of the primary and young enamel phase. The cytoplasm of ameloblasts, during primary and young enamel phases is characterized by an abundance of free ribosomes and a branular endoplasmic reticulum; but during transitional and mineralized enamel phases, the cytoplasm of these cells shows little granular endoplasmic reticulum and free ribosomes, but ehe agranular endoplasmic reticulum is present. The granular endoplasmic reticulum and free ribosomes are abundant in the cells of the intermediate layer and stellate reticulum at the ending of the young enamel phase, in the transitional enamel phase and in the beginning of the minieralized phase. During different phases of amelogenesis, in the three above referred layers of the enamel organ, were also studied the features of the Golgi apparatus the presence and topographic distribution of the pigment granules, as well as the lysosomes, desmosomes and the tonophibriles."} {"id": "PMID:1275298", "title": "Histomorphological and histochemical sutides on the female genitalia of ageing goat. II. Glands in cervix uteri.", "content": "The cervical glands of cervix uteri of goat with particular relation to their histomorphology, histochemistry and changes with reference to age, estrus cycle, pregnancy and mode of secretion have been observed and discussed.", "contents": "Histomorphological and histochemical sutides on the female genitalia of ageing goat. II. Glands in cervix uteri. The cervical glands of cervix uteri of goat with particular relation to their histomorphology, histochemistry and changes with reference to age, estrus cycle, pregnancy and mode of secretion have been observed and discussed."} {"id": "PMID:1275299", "title": "Goblet cell density in the eustachian tube in prematures and in newborn infants.", "content": "In order to determine the goblet-cell pattern in a completely normal mucosa, the entire mucosa from the Esutachian tube of 14 prematures and newborns was dissected and stained in toto by the PAS-alcian blue whole-mount method. Goblet cells were counted in many localities and the results analysed statistically. The density proved very low, but uniform in the entire Eustachian tube, 10 cells per field, corresponding to 565 cells per mm2. These findings were compared with those from a normal adult autopsy material in which the density in the pharyngeal orifice was high, but gradually decreased towards the tympanic orifice where it was as low as in prematures. It is concluded that a marked postnatal increase in the density in the tubal orifice is abnormal, whereas a physiological increase in density may be expected in the pharyngeal part of the tube. One premature, intubated for three days, exhibited a very high density in the Eustachian tube, presumably as a consequence of sudden tubal occlusion.", "contents": "Goblet cell density in the eustachian tube in prematures and in newborn infants. In order to determine the goblet-cell pattern in a completely normal mucosa, the entire mucosa from the Esutachian tube of 14 prematures and newborns was dissected and stained in toto by the PAS-alcian blue whole-mount method. Goblet cells were counted in many localities and the results analysed statistically. The density proved very low, but uniform in the entire Eustachian tube, 10 cells per field, corresponding to 565 cells per mm2. These findings were compared with those from a normal adult autopsy material in which the density in the pharyngeal orifice was high, but gradually decreased towards the tympanic orifice where it was as low as in prematures. It is concluded that a marked postnatal increase in the density in the tubal orifice is abnormal, whereas a physiological increase in density may be expected in the pharyngeal part of the tube. One premature, intubated for three days, exhibited a very high density in the Eustachian tube, presumably as a consequence of sudden tubal occlusion."} {"id": "PMID:1275300", "title": "[Comparative morphology of the trabecula septomarginalis in terrestrial mammals].", "content": "The authors studied macroscopic morphology and histologic structure of the moderator band - trabecula septomarginalis - in 100 earthly mammals. A real trabecula septomarginalis was never found in carnivora (dog and fox) because the \"anterior\" papillary muscle of the right ventricle is located on the lower part of the septum ventriculorum or at times bridge-shaped above the anteiror interventricular groove and attached on both septum and anterior wall of the right ventricle. On the opposite, in ungulates, a well-known band runs across the right ventricular chamber from the septum close to the musculus papillaris coni arteriosi up to the anterior wall close to the anterior papillary muscle. In fact the attachments lie more or less approximate to the pillars; in suidae, the trabecula usually ends on a vertical trabecula carnea just under Luschka's muscle. Three types of trabecula septomarginalis were encountered as previously described by Bortolami in ox: - Mostly (66%), the trabecula septomarginalis is a short and thick fleshy column. The ratio Length mm Thickness mm amounts to about 4 to 7 and can be regarded as reasonably constant within each variety. Moreover the quotients Length mm Height of septum MM. and Thickness of the trabecula mm Highest thickness of the anterior wall mm (measured just beneath the tricuspid attachment) keep constant in each group; thus it may be concluded that size and shape of the trabecula depend on the volume of the heart and the age of the animal. - Rarely, the trabecula looks like a tendinous cord. Such a fibrous string is nearly constant in suidae, especially in wild boar, but seldom in bovidae and cervidae. In all cases, the trabecula septomarginalis supports the right branch of the atrioventricular bundle and a thin artery which originates from the left coronary artery and branches into the right coronary vessels within the anterior papillary muscle. Some venous capillaries were also observed but only in the muscular trabeculae; they are not constant and mouth into the right ventricular chamber or run towards the septal veins around the atrioventricular node. Therefore whatever is the size, the trabecula septomarginalis must be regarded as the shortest pathway from the septum to the anteiror wall of the right ventricle and is a mere band bearing the \"right nodal pedicle\".", "contents": "[Comparative morphology of the trabecula septomarginalis in terrestrial mammals]. The authors studied macroscopic morphology and histologic structure of the moderator band - trabecula septomarginalis - in 100 earthly mammals. A real trabecula septomarginalis was never found in carnivora (dog and fox) because the \"anterior\" papillary muscle of the right ventricle is located on the lower part of the septum ventriculorum or at times bridge-shaped above the anteiror interventricular groove and attached on both septum and anterior wall of the right ventricle. On the opposite, in ungulates, a well-known band runs across the right ventricular chamber from the septum close to the musculus papillaris coni arteriosi up to the anterior wall close to the anterior papillary muscle. In fact the attachments lie more or less approximate to the pillars; in suidae, the trabecula usually ends on a vertical trabecula carnea just under Luschka's muscle. Three types of trabecula septomarginalis were encountered as previously described by Bortolami in ox: - Mostly (66%), the trabecula septomarginalis is a short and thick fleshy column. The ratio Length mm Thickness mm amounts to about 4 to 7 and can be regarded as reasonably constant within each variety. Moreover the quotients Length mm Height of septum MM. and Thickness of the trabecula mm Highest thickness of the anterior wall mm (measured just beneath the tricuspid attachment) keep constant in each group; thus it may be concluded that size and shape of the trabecula depend on the volume of the heart and the age of the animal. - Rarely, the trabecula looks like a tendinous cord. Such a fibrous string is nearly constant in suidae, especially in wild boar, but seldom in bovidae and cervidae. In all cases, the trabecula septomarginalis supports the right branch of the atrioventricular bundle and a thin artery which originates from the left coronary artery and branches into the right coronary vessels within the anterior papillary muscle. Some venous capillaries were also observed but only in the muscular trabeculae; they are not constant and mouth into the right ventricular chamber or run towards the septal veins around the atrioventricular node. Therefore whatever is the size, the trabecula septomarginalis must be regarded as the shortest pathway from the septum to the anteiror wall of the right ventricle and is a mere band bearing the \"right nodal pedicle\"."} {"id": "PMID:1275304", "title": "Comparative morphological remarks on the origin of the posterior femoral cutaneous nerve.", "content": "The origin and course of the posterior femoral cutaneous nerve were observed macroscopically in 38 Japanese adult cadavers which were dissected in the University of Hokkaido, Faculty of Medicine during the years 1971/72 and the results obtained were compared with those from some other mammals (rat, rabbit, dog and cat) and a number of bibliographical findings on the other animals. On the basis of the archetype of the pudendal plexus, the site of origin of the posterior femoral cutaneous nerve was divided into seven portions as follows: the sciatic nerve or inferior gluteal nerve (I) and its originating roots (RI), the bigeminal nerve (B) and its originating roots (RB), the part of junction of I and B (CIB), the pudendal nerve (P) and its originating roots (RP). According to the arising mode, the posterior femoral cutaneous nerve was calssified into seven types: Type A (the sciatic nerve type); the nerve arises from I and RI (horse, rat, bird, frog and salamander). Type B (the sciatic transitional type); the nerve arises from I, RI, CIB, RB and B (MAN AND MONKEY). Type C (the bigeminal nerve type); the nerve arises from CIB, RB and B (gorilla, chimpanzee, orangutan, cat and sphenodon). Type D (the pudendal transitional type); the nerve arises from CIB, RB, B, RP and P (dog). Type E (the pudendal nerve type); the nerve arises from RP and P (pig, cattle and rabbit). Type F (the mixed type); a mixture of A to E types. These various patterns in the posterior femoral cutaneous nerve may be explained by the comparative anatomical explanation on the limb medial rotation given in Braus' text-book of Anatomy (Bd. I, S. 273). From these descriptions it is reasonable to presume that the main trunk of the posterior femoral cutaneous nerve of the tetrapod below the Aves arises from the sciatic nerve and is analogous to the gluteal branches of mammals, with its main stem still retained in the pudendal nerve. If the cutaneous area supplied by the posterior femoral cutaneous nerve expands to the lateral border of the buttock in company with the lower limb medial rotation, the part between this area and that supplied by the pudendal nerve is enlarged. At first, these expanded areas are probably supplied by the branches of the pudendal nerve, which gradually become independent to become the main stem of the posterior femoral cutaneous nerve in mammals. This nerve seems, therefore, to be primarily a division of the pedendal nerve, and so in man has various types of arising patterns, A to E, in accordance with the scheme in the phylogeny. Those hypothetical changes are observed in the human sacral plexus, from which the cutaneous nerve arises with a fan-shaped overlapping.", "contents": "Comparative morphological remarks on the origin of the posterior femoral cutaneous nerve. The origin and course of the posterior femoral cutaneous nerve were observed macroscopically in 38 Japanese adult cadavers which were dissected in the University of Hokkaido, Faculty of Medicine during the years 1971/72 and the results obtained were compared with those from some other mammals (rat, rabbit, dog and cat) and a number of bibliographical findings on the other animals. On the basis of the archetype of the pudendal plexus, the site of origin of the posterior femoral cutaneous nerve was divided into seven portions as follows: the sciatic nerve or inferior gluteal nerve (I) and its originating roots (RI), the bigeminal nerve (B) and its originating roots (RB), the part of junction of I and B (CIB), the pudendal nerve (P) and its originating roots (RP). According to the arising mode, the posterior femoral cutaneous nerve was calssified into seven types: Type A (the sciatic nerve type); the nerve arises from I and RI (horse, rat, bird, frog and salamander). Type B (the sciatic transitional type); the nerve arises from I, RI, CIB, RB and B (MAN AND MONKEY). Type C (the bigeminal nerve type); the nerve arises from CIB, RB and B (gorilla, chimpanzee, orangutan, cat and sphenodon). Type D (the pudendal transitional type); the nerve arises from CIB, RB, B, RP and P (dog). Type E (the pudendal nerve type); the nerve arises from RP and P (pig, cattle and rabbit). Type F (the mixed type); a mixture of A to E types. These various patterns in the posterior femoral cutaneous nerve may be explained by the comparative anatomical explanation on the limb medial rotation given in Braus' text-book of Anatomy (Bd. I, S. 273). From these descriptions it is reasonable to presume that the main trunk of the posterior femoral cutaneous nerve of the tetrapod below the Aves arises from the sciatic nerve and is analogous to the gluteal branches of mammals, with its main stem still retained in the pudendal nerve. If the cutaneous area supplied by the posterior femoral cutaneous nerve expands to the lateral border of the buttock in company with the lower limb medial rotation, the part between this area and that supplied by the pudendal nerve is enlarged. At first, these expanded areas are probably supplied by the branches of the pudendal nerve, which gradually become independent to become the main stem of the posterior femoral cutaneous nerve in mammals. This nerve seems, therefore, to be primarily a division of the pedendal nerve, and so in man has various types of arising patterns, A to E, in accordance with the scheme in the phylogeny. Those hypothetical changes are observed in the human sacral plexus, from which the cutaneous nerve arises with a fan-shaped overlapping."} {"id": "PMID:1275306", "title": "Light microscopic and ultrastructural observations of the calcifying zone of the mandibular condyle in the rat.", "content": "The hypertrophic stage of development of the rat mandibular condyle was investigated in 16 and 26-day-old rats by electron microscopy. Interest was focused on the zone of mineralization and erosion. It was observed that capillaries invaded the lower level of the hypertrophic zone, without any previous chondroclastic resorption of calcified partitions. The partitions surrounding the hypertrophic chondrocytes were not mineralized around their entire circumference at the level of capillary penetration. The capillaries were accompanied by perivascular cells but these showed no similarities to chondroclasts. Multinucleated chondro- or osteoclasts were however present at a lower level of the subchondral area. It is suggested that there are no inherent differences with respect to the pattern of mineralization and erosion between the epiphyseal growth plate and the developing mandibular condyle.", "contents": "Light microscopic and ultrastructural observations of the calcifying zone of the mandibular condyle in the rat. The hypertrophic stage of development of the rat mandibular condyle was investigated in 16 and 26-day-old rats by electron microscopy. Interest was focused on the zone of mineralization and erosion. It was observed that capillaries invaded the lower level of the hypertrophic zone, without any previous chondroclastic resorption of calcified partitions. The partitions surrounding the hypertrophic chondrocytes were not mineralized around their entire circumference at the level of capillary penetration. The capillaries were accompanied by perivascular cells but these showed no similarities to chondroclasts. Multinucleated chondro- or osteoclasts were however present at a lower level of the subchondral area. It is suggested that there are no inherent differences with respect to the pattern of mineralization and erosion between the epiphyseal growth plate and the developing mandibular condyle."} {"id": "PMID:1275307", "title": "Numerical density of nuclei in the sheep placenta.", "content": "A method is described for estimating the number of nuclei of different cell types in the sheep placenta. The method was applied to the study of six placentas of different ages and the results have been correlated with data on the chemical composition and the physiology of the ovine placenta. In agreement with studies of placental DNA content, there is no demonstrable increase in the total number of placental nuclei in the last two months of gestation. However, the number of fetal mesenchymal nuclei decreases and there is a concomitant increase of fetal endothelial nuclei from 80 days to term. These changes correlate with a decrease in volume of the core of the placental villi and increase in umbilical blood flow.", "contents": "Numerical density of nuclei in the sheep placenta. A method is described for estimating the number of nuclei of different cell types in the sheep placenta. The method was applied to the study of six placentas of different ages and the results have been correlated with data on the chemical composition and the physiology of the ovine placenta. In agreement with studies of placental DNA content, there is no demonstrable increase in the total number of placental nuclei in the last two months of gestation. However, the number of fetal mesenchymal nuclei decreases and there is a concomitant increase of fetal endothelial nuclei from 80 days to term. These changes correlate with a decrease in volume of the core of the placental villi and increase in umbilical blood flow."} {"id": "PMID:1275308", "title": "Surface morphology of human aorta as revealed by the scanning electron microscope.", "content": "Human aorta was prepared for scanning electron microscopy using critical point drying. The aortic surface is lined by a continuous layer of squamous endothelial cells. The luminal surface of these cells contains many microvilli or microappendages and pinocytotic vesicles. In addition, at the periphery of each cell, larger marginal appendages or microfolds are present which allow the observer to see the cell boundaries clearly. The marginal folds are superficial to the cell junctions and could be observed without any staining procedures. These observations on human aorta are generally in agreement with our findings on the rabbit and guinea pig aorta and vena cava but in contrast to others who have reported the presence of ridges, intercellular bridges, and \"hair-like\" processes on the endothelial surfaces.", "contents": "Surface morphology of human aorta as revealed by the scanning electron microscope. Human aorta was prepared for scanning electron microscopy using critical point drying. The aortic surface is lined by a continuous layer of squamous endothelial cells. The luminal surface of these cells contains many microvilli or microappendages and pinocytotic vesicles. In addition, at the periphery of each cell, larger marginal appendages or microfolds are present which allow the observer to see the cell boundaries clearly. The marginal folds are superficial to the cell junctions and could be observed without any staining procedures. These observations on human aorta are generally in agreement with our findings on the rabbit and guinea pig aorta and vena cava but in contrast to others who have reported the presence of ridges, intercellular bridges, and \"hair-like\" processes on the endothelial surfaces."} {"id": "PMID:1275309", "title": "Cellular composition of the bone marrow in the chicken. I. Identification of cells.", "content": "Incorporation of Fe55 in vivo was used for verifying on radioautographs the identity of chicken bone marrow cells that are in the process of hemesyntheses. Under the experimental conditions all labeled cells may be considered to be linked with erythroid differentiation. They were classified into five maturational stages according to their morphology and capacity for DNA synthesis. Granulocytes were identified by the presence of specific granules. All mononuclear cells were classified as lymphocytes which had a pachychromatic nucleus, a high nucleocytoplasmic ratio, lacked the capacity for DNA synthesis, and resembled small lymphocytes of the bursa, spleen and bone marrow that bound, in vitro, anti-chicken gamma globulins labeled with I125. Radioautography with H3TdR was used to identify proliferating and non-proliferating members of each cell population.", "contents": "Cellular composition of the bone marrow in the chicken. I. Identification of cells. Incorporation of Fe55 in vivo was used for verifying on radioautographs the identity of chicken bone marrow cells that are in the process of hemesyntheses. Under the experimental conditions all labeled cells may be considered to be linked with erythroid differentiation. They were classified into five maturational stages according to their morphology and capacity for DNA synthesis. Granulocytes were identified by the presence of specific granules. All mononuclear cells were classified as lymphocytes which had a pachychromatic nucleus, a high nucleocytoplasmic ratio, lacked the capacity for DNA synthesis, and resembled small lymphocytes of the bursa, spleen and bone marrow that bound, in vitro, anti-chicken gamma globulins labeled with I125. Radioautography with H3TdR was used to identify proliferating and non-proliferating members of each cell population."} {"id": "PMID:1275310", "title": "Astrocytic gap junctions in the rat lateral hypothalamic area.", "content": "An extensive system of gap or nexus junctions has been found between astrocytic processes in the neuropil of the lateral hypothalamic area in the albino rat. These specialized interastrocytic junctions occur in regions of high synaptic density where neural processes are separated by the interconnected glial system. In this study, 90% of the gap junctions observed in the lateral hypothalamic neuropil are in the immediate proximity of synaptic terminals. The close morphological relationship of these glial gap junctions with synaptic contacts suggests that they may play a significant role in the process of synaptic transmission.", "contents": "Astrocytic gap junctions in the rat lateral hypothalamic area. An extensive system of gap or nexus junctions has been found between astrocytic processes in the neuropil of the lateral hypothalamic area in the albino rat. These specialized interastrocytic junctions occur in regions of high synaptic density where neural processes are separated by the interconnected glial system. In this study, 90% of the gap junctions observed in the lateral hypothalamic neuropil are in the immediate proximity of synaptic terminals. The close morphological relationship of these glial gap junctions with synaptic contacts suggests that they may play a significant role in the process of synaptic transmission."} {"id": "PMID:1275311", "title": "A proposed function for microridges on epithelial cells.", "content": "Microridges (MR), also called microvillar ridges, microplicae and cytoplasmic folds, have been noted on many epithelial surfaces. Several functions have been proposed for these structures. In the present study we examine the mechanical role that microridges may play in holding mucus to the lumenal surface to the esophagus in the trout Salmo gairdneri. Our findings support the hypothesis that the microridges help hold a protective coat of mucus to the epithelium. In addition, the complex curved or whorled arrangement of microridges appears to facilitate the spread of mucus away from goblet cells.", "contents": "A proposed function for microridges on epithelial cells. Microridges (MR), also called microvillar ridges, microplicae and cytoplasmic folds, have been noted on many epithelial surfaces. Several functions have been proposed for these structures. In the present study we examine the mechanical role that microridges may play in holding mucus to the lumenal surface to the esophagus in the trout Salmo gairdneri. Our findings support the hypothesis that the microridges help hold a protective coat of mucus to the epithelium. In addition, the complex curved or whorled arrangement of microridges appears to facilitate the spread of mucus away from goblet cells."} {"id": "PMID:1275313", "title": "Synergism between halothane and nitrous oxide in the production of nuclear abnormalities in the dividing fibroblast.", "content": "When Chinese hamster fibroblasts divide in the presence of halothane there is an increased incidence of cells with abnormal nuclei, both in mitosis and in interphase. The authors compared the effects of halothane and nitrous oxide separately and in combination. Nitrous oxide, 75 percent, alone had no significant effect compared with controls, less than 1.4 per cent of cells showing abnormalities, while halothane alone had a dose-dependent effect on both phases of the cell cycle. Halothane, 1 per cent, caused abnormalities in 7 per cent (SEM +/- 0.32) of cells in interphase and in 12 per cent (SEM +/- 0.95) of cells in mitosis, but the combination of 0.75 per cent halothane with 75 percent nitrous oxide produced 15 per cent (SEM +/- 0.68) abnormal cells in interphase and 22 per cent (SEM +/- 0.51) abnormal mitoses. Similar highly significant differences were obtained throughout the dose-response curves to as much as 4 per cent halothane in air and 2.35 per cent halothane in 75 per cent nitrous oxide. This appears to demonstrate synergism between halothane and nitrous oxide in the production of this particular side effect. In contrast, the effects of halothane and nitrous oxide on growth rate were additive.", "contents": "Synergism between halothane and nitrous oxide in the production of nuclear abnormalities in the dividing fibroblast. When Chinese hamster fibroblasts divide in the presence of halothane there is an increased incidence of cells with abnormal nuclei, both in mitosis and in interphase. The authors compared the effects of halothane and nitrous oxide separately and in combination. Nitrous oxide, 75 percent, alone had no significant effect compared with controls, less than 1.4 per cent of cells showing abnormalities, while halothane alone had a dose-dependent effect on both phases of the cell cycle. Halothane, 1 per cent, caused abnormalities in 7 per cent (SEM +/- 0.32) of cells in interphase and in 12 per cent (SEM +/- 0.95) of cells in mitosis, but the combination of 0.75 per cent halothane with 75 percent nitrous oxide produced 15 per cent (SEM +/- 0.68) abnormal cells in interphase and 22 per cent (SEM +/- 0.51) abnormal mitoses. Similar highly significant differences were obtained throughout the dose-response curves to as much as 4 per cent halothane in air and 2.35 per cent halothane in 75 per cent nitrous oxide. This appears to demonstrate synergism between halothane and nitrous oxide in the production of this particular side effect. In contrast, the effects of halothane and nitrous oxide on growth rate were additive."} {"id": "PMID:1275314", "title": "On-line systolic time intervals during anesthesia in patients with and without heart disease.", "content": "Twenty-four patients with severe, 24 with moderate, and 24 without heart disease were selected for measurements of systolic time intervals (STI) and blood pressure before and during anesthesia. In all patients anesthesia was induced with thiopental, 4 mg/kg. After tracheal intubation, 12 patients from each heart-disease class received halothane-N2O-O2 (halothane) and 12 patients from each class morphine-d-tubocurarine-N2O-O2 (MS-dTc). Thiopental increased the pre-ejection period (PEP), decreased left ventricular ejection time (LVET), and accelerated heart rate (HR). These changes were similar in patients with and without heart disease. Halothane and and MS-dTc lowered systolic blood pressure and increased PEP/LVET. With halothane but not with MS-dTc these changes were more pronounced in patients who had heart disease. Changes of the PEP/LVET ratio during halothane anesthesia were a better discriminating variable among patients without, with moderate, and with severe heart disease than were changes in systolic blood pressure.", "contents": "On-line systolic time intervals during anesthesia in patients with and without heart disease. Twenty-four patients with severe, 24 with moderate, and 24 without heart disease were selected for measurements of systolic time intervals (STI) and blood pressure before and during anesthesia. In all patients anesthesia was induced with thiopental, 4 mg/kg. After tracheal intubation, 12 patients from each heart-disease class received halothane-N2O-O2 (halothane) and 12 patients from each class morphine-d-tubocurarine-N2O-O2 (MS-dTc). Thiopental increased the pre-ejection period (PEP), decreased left ventricular ejection time (LVET), and accelerated heart rate (HR). These changes were similar in patients with and without heart disease. Halothane and and MS-dTc lowered systolic blood pressure and increased PEP/LVET. With halothane but not with MS-dTc these changes were more pronounced in patients who had heart disease. Changes of the PEP/LVET ratio during halothane anesthesia were a better discriminating variable among patients without, with moderate, and with severe heart disease than were changes in systolic blood pressure."} {"id": "PMID:1275315", "title": "Epidural anesthesia in the normotensive pregnant ewe: Effects on uterine blood flow and fetal acid-base status.", "content": "Lumbar epidural anesthesia was administered to 12 normotensive pregnant ewes. Blood pressure was maintained by intravenous fluid infusion. Six ewes received anesthesia with 1.5 per cent 2-chloroprocaine with 1:100,000 epinephrine and the remaining six received 1.5 per cent 2-chloroprocaine without epinephrine. The sensory level of anesthesia was between the umbilicus and xiphisternum. Except for a transient 14 per cent decrease in uterine blood flow in the ewes receiving 2-chloroprocaine with epinephrine, uterine blood flow remained near control values and was sufficient at all times to maintain stable fetal acid-base and blood gas values. Provided blood pressure and uterine blood flow were stable, the percentage of uterine blood flow distributed to the placenta in the absence of uterine contractions was not altered by epidural anesthesia or by addition of epinephrine to the anesthetic solution.", "contents": "Epidural anesthesia in the normotensive pregnant ewe: Effects on uterine blood flow and fetal acid-base status. Lumbar epidural anesthesia was administered to 12 normotensive pregnant ewes. Blood pressure was maintained by intravenous fluid infusion. Six ewes received anesthesia with 1.5 per cent 2-chloroprocaine with 1:100,000 epinephrine and the remaining six received 1.5 per cent 2-chloroprocaine without epinephrine. The sensory level of anesthesia was between the umbilicus and xiphisternum. Except for a transient 14 per cent decrease in uterine blood flow in the ewes receiving 2-chloroprocaine with epinephrine, uterine blood flow remained near control values and was sufficient at all times to maintain stable fetal acid-base and blood gas values. Provided blood pressure and uterine blood flow were stable, the percentage of uterine blood flow distributed to the placenta in the absence of uterine contractions was not altered by epidural anesthesia or by addition of epinephrine to the anesthetic solution."} {"id": "PMID:1275316", "title": "Dantrolene in porcine malignant hyperthermia.", "content": "The effectiveness of intravenous administration of dantrolene in prevention and treatment of fulminant malignant hyperthermia (MH) initiated by halothene and succinylcholine (SCh) in genetically susceptible swine was assessed. In six animals, prior administration of dantrolene in doses of 5 mg/kg or more prevented MH, while 1 or 3 mg/kg attenuated MH, and 0.1 mg/kg had no effect. In ten additional swine, therapy was not started until MH was fulminant. Five of these were then given supportive therapy only (discontinuation of anesthesia, hyperventilation with oxygen, surface cooling, and NaHCO3). The remaining five received the same supportive therapy, plus dantrolene (7.5 mg/kg). With supportive therapy only, arterial blood pH, Po2 and Pco2 returned toward normal, but oxygen consumption (Vo2), blood lactate, potassium (K+), catecholamines, and temperature continued to increase and the course of MH was unaltered. When dantrolene was added to supportive therapy, Vo2, lactate, K+, catecholamines, and temperature decreased, and the course of MH was dramatically slowed and, apparently, reversed.", "contents": "Dantrolene in porcine malignant hyperthermia. The effectiveness of intravenous administration of dantrolene in prevention and treatment of fulminant malignant hyperthermia (MH) initiated by halothene and succinylcholine (SCh) in genetically susceptible swine was assessed. In six animals, prior administration of dantrolene in doses of 5 mg/kg or more prevented MH, while 1 or 3 mg/kg attenuated MH, and 0.1 mg/kg had no effect. In ten additional swine, therapy was not started until MH was fulminant. Five of these were then given supportive therapy only (discontinuation of anesthesia, hyperventilation with oxygen, surface cooling, and NaHCO3). The remaining five received the same supportive therapy, plus dantrolene (7.5 mg/kg). With supportive therapy only, arterial blood pH, Po2 and Pco2 returned toward normal, but oxygen consumption (Vo2), blood lactate, potassium (K+), catecholamines, and temperature continued to increase and the course of MH was unaltered. When dantrolene was added to supportive therapy, Vo2, lactate, K+, catecholamines, and temperature decreased, and the course of MH was dramatically slowed and, apparently, reversed."} {"id": "PMID:1275317", "title": "Enzyme induction by enflurane in man.", "content": "Concentrations of 6-beta-hydroxycortisol (6-OHF), a polar metabolite of cortisol formed in the endoplasmic reticulum (microsomes) of the liver, and 17-hydroxycorticosteroids (17-OHCS) were measured in the urines of six healthy adult male volunteers exposed to a mean of 9.6 MAC-hours of enflurane anesthesia as an index of possible enzyme induction. The ratio of 6-OHF to 17-OHCS in 24-hour urine specimens collected five days before anesthesia was compared with the ratio of these metabolites in 24-hour urine specimens collected 16 to 18 hours after anesthesia. The ratio of 6-OHF to 17-OHCS increased markedly in five and decreased slightly in one volunteer following anesthesia. The results indicate that enflurane may cause induction of hepatic microsomal enzymes.", "contents": "Enzyme induction by enflurane in man. Concentrations of 6-beta-hydroxycortisol (6-OHF), a polar metabolite of cortisol formed in the endoplasmic reticulum (microsomes) of the liver, and 17-hydroxycorticosteroids (17-OHCS) were measured in the urines of six healthy adult male volunteers exposed to a mean of 9.6 MAC-hours of enflurane anesthesia as an index of possible enzyme induction. The ratio of 6-OHF to 17-OHCS in 24-hour urine specimens collected five days before anesthesia was compared with the ratio of these metabolites in 24-hour urine specimens collected 16 to 18 hours after anesthesia. The ratio of 6-OHF to 17-OHCS increased markedly in five and decreased slightly in one volunteer following anesthesia. The results indicate that enflurane may cause induction of hepatic microsomal enzymes."} {"id": "PMID:1275321", "title": "Effects of Intersept micropore filtration of blood on microaggregates and other constituents.", "content": "Micropore filtration (Intersept) of whole, stored blood was examined in two studies. In Study A, 1 unit of 14-day-old blood flowed by gravity across the filter. In Study B, the filter was preloaded by passage of 2 units of blood, and the effects on a third, consisting of 21-day-old blood, flowing under 150 mm Hg pressure, were examined. Filtration did not significantly alter erythrocyte count, total hemoglobin, plasma hemoglobin, erythrocyte fragility, plasma sodium, potassium, albumin, or globulin in either study, although some platelets and leukocytes were removed. Microaggregates, assessed by Coulter counting, screen filtration pressure, total screen proteins, wet and dry weights of material retained, and scanning electron microscopy, were satisfactorily removed over the whole range of particle sizes. Comparison with the Bentley PFS-127, Fenwal 4C2417, Pall Ultipore, and Swank IL200 filters led to the conclusion that the Intersept is the most efficient filter available at the present time for removing microaggregates during massive blood transfusion.", "contents": "Effects of Intersept micropore filtration of blood on microaggregates and other constituents. Micropore filtration (Intersept) of whole, stored blood was examined in two studies. In Study A, 1 unit of 14-day-old blood flowed by gravity across the filter. In Study B, the filter was preloaded by passage of 2 units of blood, and the effects on a third, consisting of 21-day-old blood, flowing under 150 mm Hg pressure, were examined. Filtration did not significantly alter erythrocyte count, total hemoglobin, plasma hemoglobin, erythrocyte fragility, plasma sodium, potassium, albumin, or globulin in either study, although some platelets and leukocytes were removed. Microaggregates, assessed by Coulter counting, screen filtration pressure, total screen proteins, wet and dry weights of material retained, and scanning electron microscopy, were satisfactorily removed over the whole range of particle sizes. Comparison with the Bentley PFS-127, Fenwal 4C2417, Pall Ultipore, and Swank IL200 filters led to the conclusion that the Intersept is the most efficient filter available at the present time for removing microaggregates during massive blood transfusion."} {"id": "PMID:1275325", "title": "Alteration of the response of guinea pigs to freund's complete adjuvant by ascaris extract: a preliminary histologic study.", "content": "Freund's adjuvant has been asserted to cause systemic complications in man similar to those occurring with B.C.G. vaccine. In search of factors predisposing to such complications of this vaccine, the potential role of a coexisting parasitic infestation was considered. A potentiating effect of the ascaris antigen on the pathological changes produced in guinea pigs by intraperitoneally injected Freund's complete adjuvant was noted. The pertinency of this observation to immunotherapy of cancer with B.C.G. is purely speculative.", "contents": "Alteration of the response of guinea pigs to freund's complete adjuvant by ascaris extract: a preliminary histologic study. Freund's adjuvant has been asserted to cause systemic complications in man similar to those occurring with B.C.G. vaccine. In search of factors predisposing to such complications of this vaccine, the potential role of a coexisting parasitic infestation was considered. A potentiating effect of the ascaris antigen on the pathological changes produced in guinea pigs by intraperitoneally injected Freund's complete adjuvant was noted. The pertinency of this observation to immunotherapy of cancer with B.C.G. is purely speculative."} {"id": "PMID:1275326", "title": "Temporal variability in airborne pollen concentrations.", "content": "Tests were conducted to determine the relationship between concentrations of airborne pollens and sampling time, using sequential rotoslide samplers at urban and rural locations. Short-period data showed an increase in variability with time between samples. Two-hour data showed a stronger trend for the first 12 hours but better agreement as the time between samples approached one day.", "contents": "Temporal variability in airborne pollen concentrations. Tests were conducted to determine the relationship between concentrations of airborne pollens and sampling time, using sequential rotoslide samplers at urban and rural locations. Short-period data showed an increase in variability with time between samples. Two-hour data showed a stronger trend for the first 12 hours but better agreement as the time between samples approached one day."} {"id": "PMID:1275327", "title": "Recurring and chronic urticaria: identification of etiologies.", "content": "Most of the literature on chronic urticaria has emphasized the difficulties of identifying etiology. Employing the sequential vascular response test, the authors have had a 93% success rate in determining causative factors in 156 clinic patients and of identifying specific aggravants in 85% of 300 cases.", "contents": "Recurring and chronic urticaria: identification of etiologies. Most of the literature on chronic urticaria has emphasized the difficulties of identifying etiology. Employing the sequential vascular response test, the authors have had a 93% success rate in determining causative factors in 156 clinic patients and of identifying specific aggravants in 85% of 300 cases."} {"id": "PMID:1275328", "title": "Characterization of some of the enzymes in ragweed pollen.", "content": "Ragweed pollen contains 11 esterase, 5 acid phosphatase, 2 alkaline phosphatose, 2 hexokinase, 2 glucose-6-phosphate dehydrogenase isozymes and one leucine amino peptidase band which can be separated by starch gel electrophoresis. The isozymes were distinguished from one another by their electrophoretic mobility, heat inactivation temperatures and antigenic differences.", "contents": "Characterization of some of the enzymes in ragweed pollen. Ragweed pollen contains 11 esterase, 5 acid phosphatase, 2 alkaline phosphatose, 2 hexokinase, 2 glucose-6-phosphate dehydrogenase isozymes and one leucine amino peptidase band which can be separated by starch gel electrophoresis. The isozymes were distinguished from one another by their electrophoretic mobility, heat inactivation temperatures and antigenic differences."} {"id": "PMID:1275332", "title": "Infectious bovine keratoconjunctivitis: experimental induction of infection in calves with mycoplasmas and Moraxella bovis.", "content": "Eyes of 14 calves were exposed by conjunctival instillation to cultures of either Mycoplasma conjunctivae (6 calves) or Acholeplasma laidlawii (8 calves). Calves were observed for clinical signs of infectious bovine keratoconjunctivitis (IBK), and eyes were examined for the test organisms by bacteriologic cultural technique for 60 days. Acholeplasma laidlawii became established in the eyes of 5 of 8 calves; M conjunctivae became established in the eyes of 4 of 6 calves. On day 28, eyes of 9 of the 14 calves were exposed by conjunctival instillation to Moraxella bovis, and all developed IBK. Five calves exposed to Moraxenjunctivae or A laidlawii, but not to Mor bovis, did not develop IBK. Four calves not exposed to M conjunctivae or A laidlawii, but exposed to Mor bovis, developed IBK. Mycoplasmas do not have a major role in IBK, but might produce ancillary effects similar to those of infectious bovine rhinotracheitis virus, wind, ultraviolet radiation, dust, and other irritants.", "contents": "Infectious bovine keratoconjunctivitis: experimental induction of infection in calves with mycoplasmas and Moraxella bovis. Eyes of 14 calves were exposed by conjunctival instillation to cultures of either Mycoplasma conjunctivae (6 calves) or Acholeplasma laidlawii (8 calves). Calves were observed for clinical signs of infectious bovine keratoconjunctivitis (IBK), and eyes were examined for the test organisms by bacteriologic cultural technique for 60 days. Acholeplasma laidlawii became established in the eyes of 5 of 8 calves; M conjunctivae became established in the eyes of 4 of 6 calves. On day 28, eyes of 9 of the 14 calves were exposed by conjunctival instillation to Moraxella bovis, and all developed IBK. Five calves exposed to Moraxenjunctivae or A laidlawii, but not to Mor bovis, did not develop IBK. Four calves not exposed to M conjunctivae or A laidlawii, but exposed to Mor bovis, developed IBK. Mycoplasmas do not have a major role in IBK, but might produce ancillary effects similar to those of infectious bovine rhinotracheitis virus, wind, ultraviolet radiation, dust, and other irritants."} {"id": "PMID:1275333", "title": "Scanning electron microscopy of ruminal papillae in calves fed various amounts and forms of roughage.", "content": "Twenty neonatal calves were fed milk plus 1 of 4 rations ad libitum: pelleted concentrates plus alfalfa hay, pelleted concentrates plus ground alfalfa hay, pelleted concentrates alone, or pelleted concentrates containing whey. Eight calves were killed at 4 weeks of age, and 12 calves at 6 weeks. The ruminal mucosa was examined grossly, by light microscopy, and by scanning electron microscopy. Well-developed differences among groups were evident in calves at 6 weeks of age; changes at 4 weeks were similar, but less developed. In 6-week-old calves fed concentrates plus alfalfa hay ad libitum, papillae were flattened and tongue shaped on the ventral floor of the atrium ruminis (cranial sac). Calves fed concentrates plus ground alfalfa had tongue shaped, rounded, and finger-like papillae. Calves fed concentrates alone or concentrates plus whey developed small, nodular, branched papillae which were cauliflower shaped and severly parakeratotic and were arranged on transverse folds on the floor of the atrium ruminis and on zigzag folds elsewhere in the rumen, except on the dorsal wall in contact with the gas bubble. The transition from tongue-shaped to nodular-shaped papillae under the influence of ration occurred last on the floor of the atrium ruminis. At least in 6-week-old calves, that site generally is not typical of changes in most ruminal papillae.", "contents": "Scanning electron microscopy of ruminal papillae in calves fed various amounts and forms of roughage. Twenty neonatal calves were fed milk plus 1 of 4 rations ad libitum: pelleted concentrates plus alfalfa hay, pelleted concentrates plus ground alfalfa hay, pelleted concentrates alone, or pelleted concentrates containing whey. Eight calves were killed at 4 weeks of age, and 12 calves at 6 weeks. The ruminal mucosa was examined grossly, by light microscopy, and by scanning electron microscopy. Well-developed differences among groups were evident in calves at 6 weeks of age; changes at 4 weeks were similar, but less developed. In 6-week-old calves fed concentrates plus alfalfa hay ad libitum, papillae were flattened and tongue shaped on the ventral floor of the atrium ruminis (cranial sac). Calves fed concentrates plus ground alfalfa had tongue shaped, rounded, and finger-like papillae. Calves fed concentrates alone or concentrates plus whey developed small, nodular, branched papillae which were cauliflower shaped and severly parakeratotic and were arranged on transverse folds on the floor of the atrium ruminis and on zigzag folds elsewhere in the rumen, except on the dorsal wall in contact with the gas bubble. The transition from tongue-shaped to nodular-shaped papillae under the influence of ration occurred last on the floor of the atrium ruminis. At least in 6-week-old calves, that site generally is not typical of changes in most ruminal papillae."} {"id": "PMID:1275334", "title": "Experimentally induced foot rot in feedlot cattle fed rations containing organic iodine (ethylenediamine dihydriodide) and urea.", "content": "Foot rot was experimentally induced in feedlot cattle with a mixed inoculum of Fusobacterium necrophorum (Sphaerophorus necrophus) and Bacteroides melaninogenicus. Both bacteria were isolated from the lesions. Isolates of F necrophorum from 2 of the lesions were serologically compared, using a passive hemagglutination test with the strain used to induce the lesions. These isolates were serologically similar but not identical, indicating antigenic change had occurred during animal passage. The addition of ethylenediamine dihydriodide or urea to the rations did not affect the frequency of experimentally induced foot rot.", "contents": "Experimentally induced foot rot in feedlot cattle fed rations containing organic iodine (ethylenediamine dihydriodide) and urea. Foot rot was experimentally induced in feedlot cattle with a mixed inoculum of Fusobacterium necrophorum (Sphaerophorus necrophus) and Bacteroides melaninogenicus. Both bacteria were isolated from the lesions. Isolates of F necrophorum from 2 of the lesions were serologically compared, using a passive hemagglutination test with the strain used to induce the lesions. These isolates were serologically similar but not identical, indicating antigenic change had occurred during animal passage. The addition of ethylenediamine dihydriodide or urea to the rations did not affect the frequency of experimentally induced foot rot."} {"id": "PMID:1275335", "title": "Urogenital infection and seminal excretion after inoculation of bulls and rams with chlamydiae.", "content": "Five mature rams and 4 bulls were inoculated parenterally with bovine or ovine chlamydial strains of type 1 and 2. One to 3 days later, all animals developed a chlamydemia lasting 4 to 8 days. Chlamydial agents were isolated from the semen near the end of the chlamydemic phase. All rams and 3 of 4 inoculated bulls excreted chlamydiae in the semen for 22 to 29 days. From 8 to 39 days after inoculation, selected rams or bulls were killed to test for chlamydial infection in the urogenital tract and other organs. Chlamydiae were isolated in developing chicken embryos from testis, epididymis, and accessory sex glands. Bulls examined 29 and 39 days after inoculation did not harbor chlamydiae. Chlamydiae were also not isolated from 3 control bulls which were from the same herd as the principal bulls. All inoculated bulls and rams had a group-specific chlamydial antibody response within 7 days. The titers reached maximal levels of 128 to 512 at 14 days after inoculation. Subsequently, the antibody titers decreased gradually. Seminal plasma collected at different times after animals were inoculated did not fix complement in the presence of chlamydial group antigen. The number of polymorphonuclear leukocytes in the semen increased during the experiment. The semen was grossly purulent in 2 rams inoculated with the type 2 chlamydial strain of polyarthritis.", "contents": "Urogenital infection and seminal excretion after inoculation of bulls and rams with chlamydiae. Five mature rams and 4 bulls were inoculated parenterally with bovine or ovine chlamydial strains of type 1 and 2. One to 3 days later, all animals developed a chlamydemia lasting 4 to 8 days. Chlamydial agents were isolated from the semen near the end of the chlamydemic phase. All rams and 3 of 4 inoculated bulls excreted chlamydiae in the semen for 22 to 29 days. From 8 to 39 days after inoculation, selected rams or bulls were killed to test for chlamydial infection in the urogenital tract and other organs. Chlamydiae were isolated in developing chicken embryos from testis, epididymis, and accessory sex glands. Bulls examined 29 and 39 days after inoculation did not harbor chlamydiae. Chlamydiae were also not isolated from 3 control bulls which were from the same herd as the principal bulls. All inoculated bulls and rams had a group-specific chlamydial antibody response within 7 days. The titers reached maximal levels of 128 to 512 at 14 days after inoculation. Subsequently, the antibody titers decreased gradually. Seminal plasma collected at different times after animals were inoculated did not fix complement in the presence of chlamydial group antigen. The number of polymorphonuclear leukocytes in the semen increased during the experiment. The semen was grossly purulent in 2 rams inoculated with the type 2 chlamydial strain of polyarthritis."} {"id": "PMID:1275336", "title": "Arsanilic acid-induced blindness in swine: electroretinographic and visually evoked responses.", "content": "Arsanilic acid (1,000 ppm) caused blindness in pigs within 25 to 30 days. The visually evoked response was \"nonrecordable\" in blind pigs, but was consistently recordable in normal pigs. The electroretinographic response was recordable in both normal and blind pigs, and significant differences were not apparent between results of tests of the 2 groups. Optic disk atrophy was noted ophthalmoscopically; lesions of the optic nerve are probably responsible for the nonrecordable visually evoked response.", "contents": "Arsanilic acid-induced blindness in swine: electroretinographic and visually evoked responses. Arsanilic acid (1,000 ppm) caused blindness in pigs within 25 to 30 days. The visually evoked response was \"nonrecordable\" in blind pigs, but was consistently recordable in normal pigs. The electroretinographic response was recordable in both normal and blind pigs, and significant differences were not apparent between results of tests of the 2 groups. Optic disk atrophy was noted ophthalmoscopically; lesions of the optic nerve are probably responsible for the nonrecordable visually evoked response."} {"id": "PMID:1275337", "title": "Immunoglobulins in porcine umbilical cord blood and maternal placenta.", "content": "Studies were made of the immunoglobulin (Ig) in serums from umbilical cord of newborn pigs and maternal placenta. The neutralization test for porcine parvovirus and Japanese encephalitis virus was carried out with the serum of the sow and that of the umbilical cord of the newborn pig. Comparative studies of the serums from the dam and the umbilical cord were also done with gel filtration. Of 20 umbilical cord serum samples, IgG was seen in 5 samples (25%), IgA in 1 sample (5%), and IgM in 9 samples (45%). The amount of any 1 of the 3 classes of Ig in the serums was between 13.5 and 28.0 mg/dl. Among the samples examined, 1 had both IgG and IgA and 1 had IgG and IgM, but none had both IgA and IgM and none had 3 classes of immunoglobulins (i.e., IgG, IgA, and IgM). Only 7 samples (35%) did not have any class of Ig. The IgG disappeared from the blood of hysterectomy-produced colostrum-deprived pigs at 3 days of age, and IgM disappeared when pigs were 7 days of age. Neutralization antibodies of porcine parvovirus and Japanese encephalitis virus in maternal serum were not transferred to the fetus through the placenta. Results of immunohistologic surveys indicated that the sow's Ig were not transferred to the fetus through the placenta. Therefore, it is believed that the Ig in the porcine fetus might be synthesized in certain cells in the placental tissue, and the degree of production of the Ig in the placental tissues may differ in each case. The component, which seems to be Ig, was observed as the obscure band of the beta- to gamma-globulin area in serum of the umbilical cord. Comparison was made, with gel filtration, of maternal serum and serum from the umbilical cord of the newborn pig originating from the same sow. Seemingly, the IgG in the umbilical cord serum is mainly in the lower molecular weight fraction, whereas IgG in the sow's serum was distributed in the high to low molecular weight fractions.", "contents": "Immunoglobulins in porcine umbilical cord blood and maternal placenta. Studies were made of the immunoglobulin (Ig) in serums from umbilical cord of newborn pigs and maternal placenta. The neutralization test for porcine parvovirus and Japanese encephalitis virus was carried out with the serum of the sow and that of the umbilical cord of the newborn pig. Comparative studies of the serums from the dam and the umbilical cord were also done with gel filtration. Of 20 umbilical cord serum samples, IgG was seen in 5 samples (25%), IgA in 1 sample (5%), and IgM in 9 samples (45%). The amount of any 1 of the 3 classes of Ig in the serums was between 13.5 and 28.0 mg/dl. Among the samples examined, 1 had both IgG and IgA and 1 had IgG and IgM, but none had both IgA and IgM and none had 3 classes of immunoglobulins (i.e., IgG, IgA, and IgM). Only 7 samples (35%) did not have any class of Ig. The IgG disappeared from the blood of hysterectomy-produced colostrum-deprived pigs at 3 days of age, and IgM disappeared when pigs were 7 days of age. Neutralization antibodies of porcine parvovirus and Japanese encephalitis virus in maternal serum were not transferred to the fetus through the placenta. Results of immunohistologic surveys indicated that the sow's Ig were not transferred to the fetus through the placenta. Therefore, it is believed that the Ig in the porcine fetus might be synthesized in certain cells in the placental tissue, and the degree of production of the Ig in the placental tissues may differ in each case. The component, which seems to be Ig, was observed as the obscure band of the beta- to gamma-globulin area in serum of the umbilical cord. Comparison was made, with gel filtration, of maternal serum and serum from the umbilical cord of the newborn pig originating from the same sow. Seemingly, the IgG in the umbilical cord serum is mainly in the lower molecular weight fraction, whereas IgG in the sow's serum was distributed in the high to low molecular weight fractions."} {"id": "PMID:1275338", "title": "Strongyloides ransomi: prenatal and transmammary infection of pigs of sequential litters from dams experimentally exposed as weanlings.", "content": "Prenatal infection of pigs with Strongyloides ransomi occurred in 12% of 104 pigs and in 14% of 21 litters farrowed by 13 sows experimentally exposed to infective larvae as weanlings. Transmammary passage was observed in 38 of 39 litters studied. Milk samples obtained from 14 sows showed that larvae were usually shed in the colostrum within 24 hours after farrowing; however, larvae were recovered from samples of milk of sows up to 20 days after parturition. Larvae were recovered from milk samples obtained after each parturition up to the fourth. Prenatal infection in pigs was not detected after the 1st litter.", "contents": "Strongyloides ransomi: prenatal and transmammary infection of pigs of sequential litters from dams experimentally exposed as weanlings. Prenatal infection of pigs with Strongyloides ransomi occurred in 12% of 104 pigs and in 14% of 21 litters farrowed by 13 sows experimentally exposed to infective larvae as weanlings. Transmammary passage was observed in 38 of 39 litters studied. Milk samples obtained from 14 sows showed that larvae were usually shed in the colostrum within 24 hours after farrowing; however, larvae were recovered from samples of milk of sows up to 20 days after parturition. Larvae were recovered from milk samples obtained after each parturition up to the fourth. Prenatal infection in pigs was not detected after the 1st litter."} {"id": "PMID:1275339", "title": "Enzootic calcinosis in sheep: clinical signs and pathology.", "content": "Enzootic calcinosis in Corriedale sheep was characterized by degeneration and mineralization of elastic connective tissue of aorta, arteries, lung, and kidney and by ulceration of cartilage of joints of limbs. Results of serum chemical analysis revealed low Ca X P value and significantly low, but inconsistent magnesium concentration and normal inorganic phosphorus content. The Ca:P ratio in bone was low in affected sheep. Clinicopathologically, calcinosis of sheep at Mattewara, India, appeared to be similar to the disease described as Enteque seco in South America, Naalehu disease in Hawaii, Manchester wasting disease in Jamaica, and calcinosis in central Europe, Israel, and South Africa. The disease might be due to complex mineral imbalance, although the possibility of a plant poisoning has not been ruled out.", "contents": "Enzootic calcinosis in sheep: clinical signs and pathology. Enzootic calcinosis in Corriedale sheep was characterized by degeneration and mineralization of elastic connective tissue of aorta, arteries, lung, and kidney and by ulceration of cartilage of joints of limbs. Results of serum chemical analysis revealed low Ca X P value and significantly low, but inconsistent magnesium concentration and normal inorganic phosphorus content. The Ca:P ratio in bone was low in affected sheep. Clinicopathologically, calcinosis of sheep at Mattewara, India, appeared to be similar to the disease described as Enteque seco in South America, Naalehu disease in Hawaii, Manchester wasting disease in Jamaica, and calcinosis in central Europe, Israel, and South Africa. The disease might be due to complex mineral imbalance, although the possibility of a plant poisoning has not been ruled out."} {"id": "PMID:1275340", "title": "Enzootic calcinosis in sheep: soil-plant-animal relationship.", "content": "Chemical compositions of soil, water, feeds, and forages on a farm where sheep were affected with calcinosis (experimental site) and a farm with sheep not affected with calcinosis (control site) were determined. The study lasted 1 year. It was observed that water from the experimental site had higher electrical conductivity and calcium level than from the control site. Higher conductivity indicated greater mineral content in the water. Soil from the experimental site had lower levels of potassium, nitrogen, and phosphorus and higher content of exchangeable calcium as compared with these values of the control site. Exchangeable Ca:Mg ratio for soil of the experiemntal site was twice greater than that of the control site. Forage plants of the experimental site had lower concentrations of nitrogen, phosphorus, calcium, magnesium, and copper, but higher values of potassium and sulfur. The K:Ca + Mg, K:P, and K:Ca ratios for plants from the experimental site were higher and Ca:P ratio was lower than those of the control site. Analysis of ruminal content of the affected sheep revealed higher K:Ca + Mg, K:P, and Ca:P ratios than those of the control sheep. Due to the close relationship of metabolism of calcium, phosphorus, potassium, and magnesium, evidence of the existance of their imbalances in feeds and forages of the affected farm possibly contributing to the causation of the pathologic calcification of soft tissues of the sheep has been presented.", "contents": "Enzootic calcinosis in sheep: soil-plant-animal relationship. Chemical compositions of soil, water, feeds, and forages on a farm where sheep were affected with calcinosis (experimental site) and a farm with sheep not affected with calcinosis (control site) were determined. The study lasted 1 year. It was observed that water from the experimental site had higher electrical conductivity and calcium level than from the control site. Higher conductivity indicated greater mineral content in the water. Soil from the experimental site had lower levels of potassium, nitrogen, and phosphorus and higher content of exchangeable calcium as compared with these values of the control site. Exchangeable Ca:Mg ratio for soil of the experiemntal site was twice greater than that of the control site. Forage plants of the experimental site had lower concentrations of nitrogen, phosphorus, calcium, magnesium, and copper, but higher values of potassium and sulfur. The K:Ca + Mg, K:P, and K:Ca ratios for plants from the experimental site were higher and Ca:P ratio was lower than those of the control site. Analysis of ruminal content of the affected sheep revealed higher K:Ca + Mg, K:P, and Ca:P ratios than those of the control sheep. Due to the close relationship of metabolism of calcium, phosphorus, potassium, and magnesium, evidence of the existance of their imbalances in feeds and forages of the affected farm possibly contributing to the causation of the pathologic calcification of soft tissues of the sheep has been presented."} {"id": "PMID:1275341", "title": "Distribution of chloramphenicol in some tissues and extravascular fluids of dogs after oral administration.", "content": "Chloramphenicol concentrations were assayed chemically in tissue homogenates, blood, and certain extravascular fluids of Greyhounds killed 1.5, 3, 6, and 12 hours after they were orally given the drug (50 mg/kg). The concentrations of hemoglobin in blood and tissue homogenates were used to estimate \"corrected values\" to allow for differences in vascularity of the tissues sampled. The distribution of chloramphenicol in the body was not uniform. In all sampled tissues except brain, the initial corrected values were higher than the concentrations in blood. The tissues sampled, in diminishing order of initial corrected value, were lymph node, spleen, pancreas, liver, kidney, lung, muscle, and brain. The persistence of antibiotic in different tissues varied, and in some tissues it was detectable when blood concentrations reached zero. Penetration of chloramphenicol into brain and cerebrospinal fluid was slower than in other tissues and fluids. In aqueous humor and cerebrospinal fluid, concentrations were lower than those in blood, but high concentrations were present in urine. The findings indicated that during chloramphenicol therapy it may be advantageous to select dosage frequencies according to the site of infection.", "contents": "Distribution of chloramphenicol in some tissues and extravascular fluids of dogs after oral administration. Chloramphenicol concentrations were assayed chemically in tissue homogenates, blood, and certain extravascular fluids of Greyhounds killed 1.5, 3, 6, and 12 hours after they were orally given the drug (50 mg/kg). The concentrations of hemoglobin in blood and tissue homogenates were used to estimate \"corrected values\" to allow for differences in vascularity of the tissues sampled. The distribution of chloramphenicol in the body was not uniform. In all sampled tissues except brain, the initial corrected values were higher than the concentrations in blood. The tissues sampled, in diminishing order of initial corrected value, were lymph node, spleen, pancreas, liver, kidney, lung, muscle, and brain. The persistence of antibiotic in different tissues varied, and in some tissues it was detectable when blood concentrations reached zero. Penetration of chloramphenicol into brain and cerebrospinal fluid was slower than in other tissues and fluids. In aqueous humor and cerebrospinal fluid, concentrations were lower than those in blood, but high concentrations were present in urine. The findings indicated that during chloramphenicol therapy it may be advantageous to select dosage frequencies according to the site of infection."} {"id": "PMID:1275342", "title": "Blood volume changes and production and destruction of erythrocytes in newborn dogs.", "content": "Erythrocyte, plasma, and total blood volumes were measured in dogs from birth to maturity. All of these volumes (per kilogram of body weight) were significantly greater in the dog at birth than at maturity. Erythrocyte volume decreased during neonatal and postnatal periods to less than that during adult period. Erythrocyte production and destruction were measured with a technique combining dilution method of T-1824 for blood volume measurement with uniform tagging of newly formed erythrocytes with 29Fe. Erythrocyte destruction was high during the first 2 weeks after birth.", "contents": "Blood volume changes and production and destruction of erythrocytes in newborn dogs. Erythrocyte, plasma, and total blood volumes were measured in dogs from birth to maturity. All of these volumes (per kilogram of body weight) were significantly greater in the dog at birth than at maturity. Erythrocyte volume decreased during neonatal and postnatal periods to less than that during adult period. Erythrocyte production and destruction were measured with a technique combining dilution method of T-1824 for blood volume measurement with uniform tagging of newly formed erythrocytes with 29Fe. Erythrocyte destruction was high during the first 2 weeks after birth."} {"id": "PMID:1275343", "title": "Morphologic and physical characteristics of feline infectious peritonitis virus and its growth in autochthonous peritoneal cell cultures.", "content": "Characteristic viral-type particles were seen in liver of kittens experimentally infected with the feline infectious peritonitis (FIP) agent. The particles were from 70 to 75 nm in diameter, with a central doughnut-shaped nucleoid 50 to 55 nm in diameter; numerous spikelike projections extended from their envelopes. Similar particles were seen by electron microscopy in peritoneal cell cultures derived from the peritoneal exudate of experimentally infected kittens, and viral antigens were identified in these cells by immunofluorescence. Cells and supernatant fluids from cultures containing these particles produced FIP when injected into the peritoneal cavity of kittens. The FIP agent is heat sensitive, ether labile, and relatively phenol resistant and is inactivated within 24 hours at room temperature. The FIP agent is inactivated by recommended viricidal concentrations of chlorhexidine and benzlkonium chloride.", "contents": "Morphologic and physical characteristics of feline infectious peritonitis virus and its growth in autochthonous peritoneal cell cultures. Characteristic viral-type particles were seen in liver of kittens experimentally infected with the feline infectious peritonitis (FIP) agent. The particles were from 70 to 75 nm in diameter, with a central doughnut-shaped nucleoid 50 to 55 nm in diameter; numerous spikelike projections extended from their envelopes. Similar particles were seen by electron microscopy in peritoneal cell cultures derived from the peritoneal exudate of experimentally infected kittens, and viral antigens were identified in these cells by immunofluorescence. Cells and supernatant fluids from cultures containing these particles produced FIP when injected into the peritoneal cavity of kittens. The FIP agent is heat sensitive, ether labile, and relatively phenol resistant and is inactivated within 24 hours at room temperature. The FIP agent is inactivated by recommended viricidal concentrations of chlorhexidine and benzlkonium chloride."} {"id": "PMID:1275344", "title": "Effects of uterus and prostaglandin F2alpha on corpora lutea in Mongolian gerbils and guinea pigs.", "content": "One or both uterine horns were removed on postpartum day 6 day 1=parturition in pseudopregnant gerbils. On dy 16, the corpora lutea (C) in unilaterally hysterectomized gerbils were smaller (P less than 0.05) in the ovary adjacent to an intact horn than in the ovary adjacent to a removed horn. The cL were smaller in uterine-intact than in completely hysterectomized gerbils. I n another experiment, the cl were smaller (P less than 0.05) in pseudopregnant gerbils given a single intrauterine injection of a 30- or 20-mug dose of prostaglandin F2alpha) (PGFalpha) on postpartum day 6 and theen necropsied on day 10 than in gerbils given 10-, 5-, 1-, and 0-mug doses; CL were smaller (P less than 0.05) on the side ipsilateral to the treated horn than on the opposite side, although the interaction of dose and side was not significant...", "contents": "Effects of uterus and prostaglandin F2alpha on corpora lutea in Mongolian gerbils and guinea pigs. One or both uterine horns were removed on postpartum day 6 day 1=parturition in pseudopregnant gerbils. On dy 16, the corpora lutea (C) in unilaterally hysterectomized gerbils were smaller (P less than 0.05) in the ovary adjacent to an intact horn than in the ovary adjacent to a removed horn. The cL were smaller in uterine-intact than in completely hysterectomized gerbils. I n another experiment, the cl were smaller (P less than 0.05) in pseudopregnant gerbils given a single intrauterine injection of a 30- or 20-mug dose of prostaglandin F2alpha) (PGFalpha) on postpartum day 6 and theen necropsied on day 10 than in gerbils given 10-, 5-, 1-, and 0-mug doses; CL were smaller (P less than 0.05) on the side ipsilateral to the treated horn than on the opposite side, although the interaction of dose and side was not significant..."} {"id": "PMID:1275345", "title": "Pathologic changes in ferrets exposed to pseudorabies virus.", "content": "Ferrets experimentally infected by various routes with pseudorabies virus were examined for gross and microscopic lesions. Nonsuppurative meningoencephalomyelitis, as well as visceral lesions, occurred. The incubation period seemed related to the viral dose and to the distance between the inoculation site and the central nervous system. The distribution of the lesions in the central nervous system appeared to be closely related to the peripheral nerve pathways from the inoculation sites. Other findings indicated that the lymphohematogenous route could have a role in the dissemination of the virus in infected ferrets.", "contents": "Pathologic changes in ferrets exposed to pseudorabies virus. Ferrets experimentally infected by various routes with pseudorabies virus were examined for gross and microscopic lesions. Nonsuppurative meningoencephalomyelitis, as well as visceral lesions, occurred. The incubation period seemed related to the viral dose and to the distance between the inoculation site and the central nervous system. The distribution of the lesions in the central nervous system appeared to be closely related to the peripheral nerve pathways from the inoculation sites. Other findings indicated that the lymphohematogenous route could have a role in the dissemination of the virus in infected ferrets."} {"id": "PMID:1275346", "title": "Interrelationships between athyreotic and manganese-deficient states in rats.", "content": "Possible interrelationships of manganese-deficient and hypothyroid (thiouracil treatment) states in rats were examined. Clinical signs, necropsy changes, and plasma thyroxine concentrations were determined in control rats (group A), thiouracil-treated (hypothyroid) rats (group B), rats given manganese-deficient feed (group C), and rats given thiouracil and manganese-deficient feed (group D). Clinical signs observed included a hyperemic condition of the ears in group C and D rats that was considerably more severe in the latter group. One rat from group D also had middle ear changes, as reflected by a tilting of the head. Fluid intake was severely reduced in group D rats near the end of the 60-day experimental period and resulted in marked dehydration. Pathologic change (fatty liver) was observed at necropsy in only 1 rat from group D. Thiouracil treatment of rats reduced plasma thyroxine concentration to 48 to 68% of base line from experimental days 20 to 60. The same thiouracil treatment combined with feeding a manganese-deficient ration significantly reduced plasma thyroxine concentrations to 37% of base line at day 20 and 5% of base line at day 40; the concentration at day 60 was 76% of base line, apparently approaching normal because of concentration of the plasma (and thyroxine) in the dehydrated rats. Mean adrenal gland weight was significantly less than normal in group D rats, whereas mean thyroid gland weight in this group was increased, although less than that of group B rats treated with thiouracil only. Thus, clinical signs of deficiency were enhanced when athyreotic and manganese-deficient states were combined, and plasma thyroxine concentrations were markedly decreased, giving added meaning to the need for awareness of hormonal and trace mineral status of animals.", "contents": "Interrelationships between athyreotic and manganese-deficient states in rats. Possible interrelationships of manganese-deficient and hypothyroid (thiouracil treatment) states in rats were examined. Clinical signs, necropsy changes, and plasma thyroxine concentrations were determined in control rats (group A), thiouracil-treated (hypothyroid) rats (group B), rats given manganese-deficient feed (group C), and rats given thiouracil and manganese-deficient feed (group D). Clinical signs observed included a hyperemic condition of the ears in group C and D rats that was considerably more severe in the latter group. One rat from group D also had middle ear changes, as reflected by a tilting of the head. Fluid intake was severely reduced in group D rats near the end of the 60-day experimental period and resulted in marked dehydration. Pathologic change (fatty liver) was observed at necropsy in only 1 rat from group D. Thiouracil treatment of rats reduced plasma thyroxine concentration to 48 to 68% of base line from experimental days 20 to 60. The same thiouracil treatment combined with feeding a manganese-deficient ration significantly reduced plasma thyroxine concentrations to 37% of base line at day 20 and 5% of base line at day 40; the concentration at day 60 was 76% of base line, apparently approaching normal because of concentration of the plasma (and thyroxine) in the dehydrated rats. Mean adrenal gland weight was significantly less than normal in group D rats, whereas mean thyroid gland weight in this group was increased, although less than that of group B rats treated with thiouracil only. Thus, clinical signs of deficiency were enhanced when athyreotic and manganese-deficient states were combined, and plasma thyroxine concentrations were markedly decreased, giving added meaning to the need for awareness of hormonal and trace mineral status of animals."} {"id": "PMID:1275347", "title": "Comparative hematology: studies on goats.", "content": "Results of blood coagulation and hematologic studies on 6 goats, each tested 3 times, were compared to the values seen in persons. Special blood platelet studies were done on an additional goat. Blood coagulation values in the goats and in persons were similar, with these exceptions: In the goat, activated partial thromboplastin time was shorter and thrombin time was longer; one-stage assays of factors V, VIII, and IX were very high, and platelets aggregated poorly epinephrine and ristocetin. Both platelets and erythrocytes were small. On scanning electron microscopy, the erythrocytes appeared as flat disks or triangles, occasionally having a dimpled center, compared to the deeply dimpled doughnut shape of the larger human erythrocytes. Osmotic fragility of these small erythrocytes was greater than that of their human counterparts. By transmission electron microscopy of ultrathin sections of goat buffy coat, platelets had fine structures similar to those of human platelets. Unlike in human platelets, most of the dense bodies in goat platelets were surrounded by clear vacuoles. Biochemical studies showed higher than human levels of phosphorus, chloride, sodium, alkaline phosphatase, and serum glutamic oxaloacetic transaminase.", "contents": "Comparative hematology: studies on goats. Results of blood coagulation and hematologic studies on 6 goats, each tested 3 times, were compared to the values seen in persons. Special blood platelet studies were done on an additional goat. Blood coagulation values in the goats and in persons were similar, with these exceptions: In the goat, activated partial thromboplastin time was shorter and thrombin time was longer; one-stage assays of factors V, VIII, and IX were very high, and platelets aggregated poorly epinephrine and ristocetin. Both platelets and erythrocytes were small. On scanning electron microscopy, the erythrocytes appeared as flat disks or triangles, occasionally having a dimpled center, compared to the deeply dimpled doughnut shape of the larger human erythrocytes. Osmotic fragility of these small erythrocytes was greater than that of their human counterparts. By transmission electron microscopy of ultrathin sections of goat buffy coat, platelets had fine structures similar to those of human platelets. Unlike in human platelets, most of the dense bodies in goat platelets were surrounded by clear vacuoles. Biochemical studies showed higher than human levels of phosphorus, chloride, sodium, alkaline phosphatase, and serum glutamic oxaloacetic transaminase."} {"id": "PMID:1275348", "title": "Lactic acid-utilizing bacteria in ruminal fluid of a steer adapted from hay feeding to a high-grain ration.", "content": "A mature, rumen-cannulated steer fed Coastal Bermuda grass hay for 8 weeks was adapted to a high-grain ration by stepwise increases in grain over a period of 4 weeks. The grain rations had concentrate-to-roughage ratios of 40:60, 70:30, and 85:15 and were fed for 10, 7, and 11 days, respectively. Numerical estimates of lactate-utilizing bacteria in ruminal fluid of the steer the last 3 days each ration was fed were made by colony counts. Lactate-utilizing bacteria were identified as Megasphaera elsdenii, Peptococcus asaccharolyticus, and Selenomonas ruminantium. Maximal numbers of lactate-utilizing bacteria were observed in the ruminal fluid of the steer during feeding the concentrate-to-roughage ration of 70:30.", "contents": "Lactic acid-utilizing bacteria in ruminal fluid of a steer adapted from hay feeding to a high-grain ration. A mature, rumen-cannulated steer fed Coastal Bermuda grass hay for 8 weeks was adapted to a high-grain ration by stepwise increases in grain over a period of 4 weeks. The grain rations had concentrate-to-roughage ratios of 40:60, 70:30, and 85:15 and were fed for 10, 7, and 11 days, respectively. Numerical estimates of lactate-utilizing bacteria in ruminal fluid of the steer the last 3 days each ration was fed were made by colony counts. Lactate-utilizing bacteria were identified as Megasphaera elsdenii, Peptococcus asaccharolyticus, and Selenomonas ruminantium. Maximal numbers of lactate-utilizing bacteria were observed in the ruminal fluid of the steer during feeding the concentrate-to-roughage ration of 70:30."} {"id": "PMID:1275349", "title": "Survey of anaplasmosis in elk of the Clearwater National Forest (Idaho).", "content": "Samples of blood from 27 free-roaming elk (Cervus canadensis canadensis) from the Clearwater National Forest in north central Idaho were tested by the rapid card agglutination test and complement-fixation test for the presence of antibodies against Anaplasma marginale. The serum card test and complement-fixation test gave incomplete and false-positive reactions; the plasma card test did not give any reactions. Anaplasma bodies or other blood parasites were not observed in stained smears of elk blood. Blood from 11 elk, including 2 that were serum card test-positive, did not produce clinical, hematologic, or serologic evidence of infection in 3 anaplasmosis-susceptible bovine calves.", "contents": "Survey of anaplasmosis in elk of the Clearwater National Forest (Idaho). Samples of blood from 27 free-roaming elk (Cervus canadensis canadensis) from the Clearwater National Forest in north central Idaho were tested by the rapid card agglutination test and complement-fixation test for the presence of antibodies against Anaplasma marginale. The serum card test and complement-fixation test gave incomplete and false-positive reactions; the plasma card test did not give any reactions. Anaplasma bodies or other blood parasites were not observed in stained smears of elk blood. Blood from 11 elk, including 2 that were serum card test-positive, did not produce clinical, hematologic, or serologic evidence of infection in 3 anaplasmosis-susceptible bovine calves."} {"id": "PMID:1275350", "title": "Efficacy of divided doses of fospirate against immature Echinococcus granulosus infections in dogs.", "content": "Seventy dogs were used to evaluate efficacy of divided doses of fospirate against immature Echinococcus granulosus infections in dogs. Dose rates of 10 to 80 mg/kg given on 1 or 2 occasions resulted in the clearance of 70.6 to 94.5% of expected worm numbers. At least 3 treatments may be required before dogs can be free from E granulosus. Vomiting, which occurred in dogs given doses of 40 mg or more/kg, seemed to interfere with anthelmintic efficacy in some dogs.", "contents": "Efficacy of divided doses of fospirate against immature Echinococcus granulosus infections in dogs. Seventy dogs were used to evaluate efficacy of divided doses of fospirate against immature Echinococcus granulosus infections in dogs. Dose rates of 10 to 80 mg/kg given on 1 or 2 occasions resulted in the clearance of 70.6 to 94.5% of expected worm numbers. At least 3 treatments may be required before dogs can be free from E granulosus. Vomiting, which occurred in dogs given doses of 40 mg or more/kg, seemed to interfere with anthelmintic efficacy in some dogs."} {"id": "PMID:1275351", "title": "Efficacy of divided doses of GS-23654 against immature Echinococcus granulosus infections in dogs.", "content": "One hundred dogs were used to evaluate the efficacy of GS-23654 (4-nitro-4'-isothiocyano-diphenyl-ether) against immature Echinococcus granulosus. A 25% suspension of active ingredient was administered at dose rates of 100, 200, or 400 mg/kg of body weight on 1, 2, or 3 occasions. Anthelmintic efficacy was dosage dependent and increased with the number of times the dosage was repeated. At none of the treatment schedules tested were all worms eliminated from all dogs, although 92.6% of the expected number of worms were eliminated from dogs given 400 mg/kg on 3 occasions.", "contents": "Efficacy of divided doses of GS-23654 against immature Echinococcus granulosus infections in dogs. One hundred dogs were used to evaluate the efficacy of GS-23654 (4-nitro-4'-isothiocyano-diphenyl-ether) against immature Echinococcus granulosus. A 25% suspension of active ingredient was administered at dose rates of 100, 200, or 400 mg/kg of body weight on 1, 2, or 3 occasions. Anthelmintic efficacy was dosage dependent and increased with the number of times the dosage was repeated. At none of the treatment schedules tested were all worms eliminated from all dogs, although 92.6% of the expected number of worms were eliminated from dogs given 400 mg/kg on 3 occasions."} {"id": "PMID:1275353", "title": "Chronic bifascicular block: evaluation of familial factors.", "content": "We studied whether familial factors are significant in chronic bifascicular block. One hundred thirty-four first- and second-degree relatives of 44 outpatients with chronic bifascicular block were examined. These relatives were studied to ascertain the presence or absence of cardiac disease and conduction defects. A race-, age-, and sex-matched control group (age range, 18 to 65) was randomly chosen from a population of employed volunteers for comparison purposes. The study group had a significantly greater frequency of conduction defects than the control group (24/95 versus 10/95, P less than 0.02). Study group members less than 18 years of age (32 patients) had a similar frequency of conduction defects when compared with patients described in the literature. In study group members older than 65 years, 5 out of 7 had conduction defects, a high frequency. In conclusion, the findings suggest an age-related familial tendency to conduction disease among relatives of patients with chronic bifascicular block.", "contents": "Chronic bifascicular block: evaluation of familial factors. We studied whether familial factors are significant in chronic bifascicular block. One hundred thirty-four first- and second-degree relatives of 44 outpatients with chronic bifascicular block were examined. These relatives were studied to ascertain the presence or absence of cardiac disease and conduction defects. A race-, age-, and sex-matched control group (age range, 18 to 65) was randomly chosen from a population of employed volunteers for comparison purposes. The study group had a significantly greater frequency of conduction defects than the control group (24/95 versus 10/95, P less than 0.02). Study group members less than 18 years of age (32 patients) had a similar frequency of conduction defects when compared with patients described in the literature. In study group members older than 65 years, 5 out of 7 had conduction defects, a high frequency. In conclusion, the findings suggest an age-related familial tendency to conduction disease among relatives of patients with chronic bifascicular block."} {"id": "PMID:1275354", "title": "Normal diluting capacity in hyponatremic patients. Reset osmostat or a variant of the syndrome of inappropriate antidiuretic hormone secretion.", "content": "Four patients with chronic illnesses and stable hyponatremia and plasma hypotonicity had normal urinary diluting capacity, with excretion of greater than 80% of a standard water load (20 ml/kg) within 4 hours and maintenance of a urine osmolality less than 100 mosmol/kg, during sustained water diuresis. Administration of a chronic salt load did not correct the hyponatremia. However, it was stabilized after treatment of the underlying medical condition. These subjects may represent a true resetting of the osmostat or a variant of the syndrome of inappropriate antidiuretic hormone secretion.", "contents": "Normal diluting capacity in hyponatremic patients. Reset osmostat or a variant of the syndrome of inappropriate antidiuretic hormone secretion. Four patients with chronic illnesses and stable hyponatremia and plasma hypotonicity had normal urinary diluting capacity, with excretion of greater than 80% of a standard water load (20 ml/kg) within 4 hours and maintenance of a urine osmolality less than 100 mosmol/kg, during sustained water diuresis. Administration of a chronic salt load did not correct the hyponatremia. However, it was stabilized after treatment of the underlying medical condition. These subjects may represent a true resetting of the osmostat or a variant of the syndrome of inappropriate antidiuretic hormone secretion."} {"id": "PMID:1275355", "title": "Leukemia and lymphoma patients linked by prior social contact. Evaluation using a case-control approach.", "content": "A case-control approach was used to evaluate whether patients with leukemia or lymphoma have a greater than expected tendency to have had prior close personal associations. Two census enumeration districts in different states with low population mobility were chosen, and each resident who had developed leukemia or lymphoma during a predetermined fixed interval was ascertained by review of tumor registry records. For each patient, a resident of the area was selected as a control matched for age, sex, race, and geographic location as of the time of diagnosis. Close personal associations between patients, controls, and both were determined by interviewing. In Area 1 the 8 patients had 11 social links (3 direct, 8 indirect) and the controls had 2 (both direct); P=0.0156, one-tailed significance test. In Area 2, the 21 patients had 21 close links (15 direct, 6 indirect) whereas the controls had 10 (direct 8, indirect 2; 0.25 greater than P greater than 0.20).", "contents": "Leukemia and lymphoma patients linked by prior social contact. Evaluation using a case-control approach. A case-control approach was used to evaluate whether patients with leukemia or lymphoma have a greater than expected tendency to have had prior close personal associations. Two census enumeration districts in different states with low population mobility were chosen, and each resident who had developed leukemia or lymphoma during a predetermined fixed interval was ascertained by review of tumor registry records. For each patient, a resident of the area was selected as a control matched for age, sex, race, and geographic location as of the time of diagnosis. Close personal associations between patients, controls, and both were determined by interviewing. In Area 1 the 8 patients had 11 social links (3 direct, 8 indirect) and the controls had 2 (both direct); P=0.0156, one-tailed significance test. In Area 2, the 21 patients had 21 close links (15 direct, 6 indirect) whereas the controls had 10 (direct 8, indirect 2; 0.25 greater than P greater than 0.20)."} {"id": "PMID:1275356", "title": "Survivors of cancer in childhood.", "content": "Late effects of childhood cancer in 142 patients, presently aged 18 years and older, were examined with a medical record review and questionnaire survey. Seventy-four patients (52%) had major defects in treated organs, while 17 (12%) developed second primary neoplasms (10 malignancies and 7 benign tumors). Despite these disorders, most patients had fully active lives. Eighty-six (61%) had attended college, and many were employed as professionals or managers. Seventy-five (53%) were married; 46 had progeny. Disabling psychological illness attributed to cancer in childhood was uncommon. These findings indicate the potential for high quality of extended life for most survivors of childhood cancer. Comprehensive long-term care of these patients may further reduce adverse physiologic and psychosocial sequelae.", "contents": "Survivors of cancer in childhood. Late effects of childhood cancer in 142 patients, presently aged 18 years and older, were examined with a medical record review and questionnaire survey. Seventy-four patients (52%) had major defects in treated organs, while 17 (12%) developed second primary neoplasms (10 malignancies and 7 benign tumors). Despite these disorders, most patients had fully active lives. Eighty-six (61%) had attended college, and many were employed as professionals or managers. Seventy-five (53%) were married; 46 had progeny. Disabling psychological illness attributed to cancer in childhood was uncommon. These findings indicate the potential for high quality of extended life for most survivors of childhood cancer. Comprehensive long-term care of these patients may further reduce adverse physiologic and psychosocial sequelae."} {"id": "PMID:1275357", "title": "Therapy of Staphylococcus aureus bacteremia associated with a removable focus of infection.", "content": "We did a retrospective study of Staphylococcus aureus bacteremia--from removable foci of infection--treated with short course antimicrobial therapy. Patients with S. aureus endocarditis were excluded from our study. The majority of patients had sepsis from intravascular devices. After removal of the focus of bacteremia, antibiotics were administered for a mean period of 15.2 days. There were no relapses, and no patient developed endocarditis. A 10- to 21-day antibiotic regimen can be curative in S. aureus bacteremia associated with a removable focus of infection.", "contents": "Therapy of Staphylococcus aureus bacteremia associated with a removable focus of infection. We did a retrospective study of Staphylococcus aureus bacteremia--from removable foci of infection--treated with short course antimicrobial therapy. Patients with S. aureus endocarditis were excluded from our study. The majority of patients had sepsis from intravascular devices. After removal of the focus of bacteremia, antibiotics were administered for a mean period of 15.2 days. There were no relapses, and no patient developed endocarditis. A 10- to 21-day antibiotic regimen can be curative in S. aureus bacteremia associated with a removable focus of infection."} {"id": "PMID:1275358", "title": "An \"experimental\" epidemic of Reiter's syndrome revisited. Follow-up evidence on genetic and environmental factors.", "content": "The relation between a specific infective event (shigellosis), a specific disease entity (Reiter's syndrome), and a specific histocompatibility antigen (HL-A B27) is documented by follow-up study of an epidemic of post-Shigella Reiter's syndrome. Five of the original 10 patients have been traced, HL-A typed, and clinically assessed 13 years after the initial episode. One of the 5 has minimal disease, remains symptom-free, and is HL-A B27-negative. The remaining 4 have followed a chronic course, have persistent active disease, and are HL-A B27-positive. It is estimated that after this single episode of shigellosis, from one sixth to one third of the persons who were HL-A B27-positive developed Reiter's syndrome. The prognosis for postdysenteric Reiter's syndrome must be guarded, especially in the subject who is B27-positive.", "contents": "An \"experimental\" epidemic of Reiter's syndrome revisited. Follow-up evidence on genetic and environmental factors. The relation between a specific infective event (shigellosis), a specific disease entity (Reiter's syndrome), and a specific histocompatibility antigen (HL-A B27) is documented by follow-up study of an epidemic of post-Shigella Reiter's syndrome. Five of the original 10 patients have been traced, HL-A typed, and clinically assessed 13 years after the initial episode. One of the 5 has minimal disease, remains symptom-free, and is HL-A B27-negative. The remaining 4 have followed a chronic course, have persistent active disease, and are HL-A B27-positive. It is estimated that after this single episode of shigellosis, from one sixth to one third of the persons who were HL-A B27-positive developed Reiter's syndrome. The prognosis for postdysenteric Reiter's syndrome must be guarded, especially in the subject who is B27-positive."} {"id": "PMID:1275365", "title": "Hereditary angioedema: the clinical syndrome and its management.", "content": "Hereditary angioedema is manifested by attacks of swelling of the extremities, face, trunk, airway, or abdominal viscera, occurring spontaneously or secondary to trauma. It is inherited as an autosomal dominant trait and is due to deficient activity of the inhibitor of the activated first component of complement. The clinical diagnosis can be confirmed by the findings of low levels of C4 or C1 esterase inhibitor activity, or both. Therapy may be divided into three phases: long-term prophylaxis of attacks, short-term prophylaxis of attacks, and treatment of acute attacks. Long-term prophylaxis may be achieved with antifibrinolytic agents and androgens. Short-term prophylaxis with these agents and plasma transfusions has been successful. Specific therapy for acute attacks is not available, but good supportive care, together with a knowledge of the course of the disease, can prevent asphyxiation from airway obstruction. Before the advent of therapy, mortality was reported as high as 30%.", "contents": "Hereditary angioedema: the clinical syndrome and its management. Hereditary angioedema is manifested by attacks of swelling of the extremities, face, trunk, airway, or abdominal viscera, occurring spontaneously or secondary to trauma. It is inherited as an autosomal dominant trait and is due to deficient activity of the inhibitor of the activated first component of complement. The clinical diagnosis can be confirmed by the findings of low levels of C4 or C1 esterase inhibitor activity, or both. Therapy may be divided into three phases: long-term prophylaxis of attacks, short-term prophylaxis of attacks, and treatment of acute attacks. Long-term prophylaxis may be achieved with antifibrinolytic agents and androgens. Short-term prophylaxis with these agents and plasma transfusions has been successful. Specific therapy for acute attacks is not available, but good supportive care, together with a knowledge of the course of the disease, can prevent asphyxiation from airway obstruction. Before the advent of therapy, mortality was reported as high as 30%."} {"id": "PMID:1275366", "title": "Practice habits in a group of eight internists.", "content": "A method was devised to offer a group of internists a system by which to analyze their practices, allowing them to identify areas where a change in practice habits might be beneficial. More than 3000 encounters between patients and internists in an eight-man group were analyzed for a number of variables. Significant differences existed between physicians as to the percentage of encounters that were physician-initiated rather than patient-initiated. Disposition of the encounters also varied significantly. The effect that the recycling of patients has on productivity, cost, and use of hospital facilities is discussed. In addition to geographic and specialty maldistribution, the maldistribution of physician time is a significant barrier to meeting the demands for medical care.", "contents": "Practice habits in a group of eight internists. A method was devised to offer a group of internists a system by which to analyze their practices, allowing them to identify areas where a change in practice habits might be beneficial. More than 3000 encounters between patients and internists in an eight-man group were analyzed for a number of variables. Significant differences existed between physicians as to the percentage of encounters that were physician-initiated rather than patient-initiated. Disposition of the encounters also varied significantly. The effect that the recycling of patients has on productivity, cost, and use of hospital facilities is discussed. In addition to geographic and specialty maldistribution, the maldistribution of physician time is a significant barrier to meeting the demands for medical care."} {"id": "PMID:1275388", "title": "Evaluation of the techniques used for investigating the in vitro synthesis of bromegrass mosaic virus RNA.", "content": "The paper is dealing with the study of RNA polymerase activity using endogenous RNA templates in extracts of leaves infected with bromegrass mosaic virus (BMV). The in vitro labeling of BMV-RNA in such extracts is associated with a particulate replication complex which is able to synthesize totally or partially single-stranded BMV-RNA under conditions where exogenous BMV-RNA (purified from the virus) is rapidly degraded. This suggests that rapidly-labeled BMV-RNA is protected from endogenous nuclease effect.", "contents": "Evaluation of the techniques used for investigating the in vitro synthesis of bromegrass mosaic virus RNA. The paper is dealing with the study of RNA polymerase activity using endogenous RNA templates in extracts of leaves infected with bromegrass mosaic virus (BMV). The in vitro labeling of BMV-RNA in such extracts is associated with a particulate replication complex which is able to synthesize totally or partially single-stranded BMV-RNA under conditions where exogenous BMV-RNA (purified from the virus) is rapidly degraded. This suggests that rapidly-labeled BMV-RNA is protected from endogenous nuclease effect."} {"id": "PMID:1275394", "title": "Host and virus specific RNA polymerases in alfalfa mosaic virus infected tobacco.", "content": "The particulate fraction of a homogenate of alfalfa mosaic virus infected tobacco was found to contain the viral replicase, and one or more host-specific RNA-polymerases. Using an endogeneous template, the membrane-bound replicase incorporates 3H-CTP in virion-type RNA. The synthesized RNA is part of a replicative intermediate; after RN-ase-treatment the product comigrates with viral double-stranded RNA in polyacrylamide gels. A preliminary characterization of this double-stranded RNA was made by RNA-RNA hybridization. Treatment of the particulate fraction with lubrol releases a host-specific RNA-polymerase. The activity of this enzyme is completely dependent on exogeneous template-RNA. Probably only a very small region of the template is transcribed. After washing with lubrol, the particulate fraction still contains the viral replicase. When this fraction is resuspended in a Mg++-deficient buffer, about 60% of the enzyme activity is released into the supernatant. No such activity is found in a comparable extract of healthy leaves.", "contents": "Host and virus specific RNA polymerases in alfalfa mosaic virus infected tobacco. The particulate fraction of a homogenate of alfalfa mosaic virus infected tobacco was found to contain the viral replicase, and one or more host-specific RNA-polymerases. Using an endogeneous template, the membrane-bound replicase incorporates 3H-CTP in virion-type RNA. The synthesized RNA is part of a replicative intermediate; after RN-ase-treatment the product comigrates with viral double-stranded RNA in polyacrylamide gels. A preliminary characterization of this double-stranded RNA was made by RNA-RNA hybridization. Treatment of the particulate fraction with lubrol releases a host-specific RNA-polymerase. The activity of this enzyme is completely dependent on exogeneous template-RNA. Probably only a very small region of the template is transcribed. After washing with lubrol, the particulate fraction still contains the viral replicase. When this fraction is resuspended in a Mg++-deficient buffer, about 60% of the enzyme activity is released into the supernatant. No such activity is found in a comparable extract of healthy leaves."} {"id": "PMID:1275398", "title": "Transitional control in Semliki forest virus infected cells.", "content": "The cistron of the 42 S RNA, which codes for other than structural proteins, is poorly translated in the middle of the growth cycle. The translational control operating in the infected cells is not expressed in cell-free protein synthesising systems programmed with the 42 S RNA, since mostly non-structural proteins are made in vitro. One of our temperature-sensitive mutants of SFV, ts-1, directs the synthesis of two non-structural proteins with molecular weights of 78,000 (ns-78) and 86,000 (ns-86) but only at the restrictive temperature. This indicates that the synthesis of the non-structural proteins is controlled by viral rather than cellular factor(s). Temperature shift experiments revealed that the control mechanism was only slowly affected by the change of the temperature.", "contents": "Transitional control in Semliki forest virus infected cells. The cistron of the 42 S RNA, which codes for other than structural proteins, is poorly translated in the middle of the growth cycle. The translational control operating in the infected cells is not expressed in cell-free protein synthesising systems programmed with the 42 S RNA, since mostly non-structural proteins are made in vitro. One of our temperature-sensitive mutants of SFV, ts-1, directs the synthesis of two non-structural proteins with molecular weights of 78,000 (ns-78) and 86,000 (ns-86) but only at the restrictive temperature. This indicates that the synthesis of the non-structural proteins is controlled by viral rather than cellular factor(s). Temperature shift experiments revealed that the control mechanism was only slowly affected by the change of the temperature."} {"id": "PMID:1275401", "title": "Separation studies of TMV replicase.", "content": "By means of affinity chromatography RNA-agarose a partial purification of a soluble TMV replicase is obtained in addition to a poly(U) polymerase when extracts of fresh, systemically TMV-infected tobacco leaves are used. An active replicase fraction always shows a certain amount of poly(U) polymerase. The replicase is inactivated by electrophoresis and the enzyme shows a harmful adsorption to certain supporting materials. When a purified replicase fraction, or an extract from frozen infected leaves, was gel filtrated on Sephadex G-75 in 50 mM Tris-HC1 pH 7.2, three peaks of replicase activity could be detected. Peak I was found in the void volume, peak II was elute with about 1.8 times the void volume and peak III with about 2.6 times the void volume. The activities of peaks II and III had very short half-times. Peak II was not obtained with extracts of frozen healthy leaves.", "contents": "Separation studies of TMV replicase. By means of affinity chromatography RNA-agarose a partial purification of a soluble TMV replicase is obtained in addition to a poly(U) polymerase when extracts of fresh, systemically TMV-infected tobacco leaves are used. An active replicase fraction always shows a certain amount of poly(U) polymerase. The replicase is inactivated by electrophoresis and the enzyme shows a harmful adsorption to certain supporting materials. When a purified replicase fraction, or an extract from frozen infected leaves, was gel filtrated on Sephadex G-75 in 50 mM Tris-HC1 pH 7.2, three peaks of replicase activity could be detected. Peak I was found in the void volume, peak II was elute with about 1.8 times the void volume and peak III with about 2.6 times the void volume. The activities of peaks II and III had very short half-times. Peak II was not obtained with extracts of frozen healthy leaves."} {"id": "PMID:1275405", "title": "Amino acid accepting structures in tymovirus RNAs.", "content": "We have shown that the 3' terminal nucleotide of tymovirus RNA binds valine as do tRNAs. We have mainly studied eggplant mosaic virus which presents two types of particles. The heavy particle contains the genome which binds valine and a 4S satellite RNA esterified by lysine. The light particle contains 4S RNAs, possessing various acceptor capacities. Among these 4S RNAs we have identified the host plant tRNAsVal, a single tRNA Lys and probably the moiety of the genome which accepts valine.", "contents": "Amino acid accepting structures in tymovirus RNAs. We have shown that the 3' terminal nucleotide of tymovirus RNA binds valine as do tRNAs. We have mainly studied eggplant mosaic virus which presents two types of particles. The heavy particle contains the genome which binds valine and a 4S satellite RNA esterified by lysine. The light particle contains 4S RNAs, possessing various acceptor capacities. Among these 4S RNAs we have identified the host plant tRNAsVal, a single tRNA Lys and probably the moiety of the genome which accepts valine."} {"id": "PMID:1275406", "title": "Location, rate and asymmetry of ds-RNA synthesis during replication of TYMV in Chinese cabbage.", "content": "The ds-RNA induced by TYMV infection in the nuclei of infected Chinese cabbage leaf cells became labelled with [32P]phosphate most rapidly before production of virus could be detected. In contrast, the ds-RNA associated with the chloroplasts became labelled most rapidly during the period of maximum virus production.", "contents": "Location, rate and asymmetry of ds-RNA synthesis during replication of TYMV in Chinese cabbage. The ds-RNA induced by TYMV infection in the nuclei of infected Chinese cabbage leaf cells became labelled with [32P]phosphate most rapidly before production of virus could be detected. In contrast, the ds-RNA associated with the chloroplasts became labelled most rapidly during the period of maximum virus production."} {"id": "PMID:1275410", "title": "Towards an understanding of viroid nature and replication.", "content": "In leaf strips and in nuclei isolated from potato spindle tuber viroid (PSTV)-infected tomato, incorporation of [3H]UMP into PSTV is shown to be inhibited by pre-treatment of the leaf-strips with actinomycin D. These results demonstrate that PSTV is synthesized in the cell nucleus and that replication may occur from a DNA template.", "contents": "Towards an understanding of viroid nature and replication. In leaf strips and in nuclei isolated from potato spindle tuber viroid (PSTV)-infected tomato, incorporation of [3H]UMP into PSTV is shown to be inhibited by pre-treatment of the leaf-strips with actinomycin D. These results demonstrate that PSTV is synthesized in the cell nucleus and that replication may occur from a DNA template."} {"id": "PMID:1275430", "title": "Environmental correlations of skin colour.", "content": "Skin colour data obtained by reflectance spectrophotometry on indigenous populations are compared with environmental variables--latitude, temperature, humidity and altitude. Association with latitude predominates at all wavelengths. Temperatures show a small but appreciable association at the shorter wavelengths, humidity at wavelengths above 595 nm. Over 80 per cent of the total interpopulation variance at each wave length is accounted for by these variables, more at the shorter wavelengths. It is suggested that skin colour should be regarded as a complex of entities of differing selective values rather than a single entity.", "contents": "Environmental correlations of skin colour. Skin colour data obtained by reflectance spectrophotometry on indigenous populations are compared with environmental variables--latitude, temperature, humidity and altitude. Association with latitude predominates at all wavelengths. Temperatures show a small but appreciable association at the shorter wavelengths, humidity at wavelengths above 595 nm. Over 80 per cent of the total interpopulation variance at each wave length is accounted for by these variables, more at the shorter wavelengths. It is suggested that skin colour should be regarded as a complex of entities of differing selective values rather than a single entity."} {"id": "PMID:1275431", "title": "Biological correlates of modernization in a Guatemalan highland municipio.", "content": "The demographic correlates of modernization were studied in a municipio of the Guatemalan highlands using, as indicators of modernization, the introduction of chemical fertilizers and of a religous revitalization movement. Accion Catolica. Records, taken from interviews, of 340 women divided into declines (decennial groups) within ten-year birth cohorts extending from before 1925 to 1954, were checked for representativeness against the birth registries for the entire municipio for the years 1965-69.", "contents": "Biological correlates of modernization in a Guatemalan highland municipio. The demographic correlates of modernization were studied in a municipio of the Guatemalan highlands using, as indicators of modernization, the introduction of chemical fertilizers and of a religous revitalization movement. Accion Catolica. Records, taken from interviews, of 340 women divided into declines (decennial groups) within ten-year birth cohorts extending from before 1925 to 1954, were checked for representativeness against the birth registries for the entire municipio for the years 1965-69."} {"id": "PMID:1275432", "title": "Comments on the critical metabolic mass and the age of menarche.", "content": "Data from Frisch and Revelle (1971) and Frisch et al. (1973) are used to show that some of their biological conclusions relating body composition to age at menarche follow directly from arithmetical operations on the two observed items of information: weight and height. This emphasizes the dangers of drawing biological conclusions from derived, as opposed to observed, data. The hypothesis that an age-unrelated critical body weight triggers off menarche is examined in relation to preliminary data from a longitudinal study of adolescent girls. It is unacceptable because: (a) mean weights at menarche showed an upward trend with increasing age; (b) for given body weights the proportion of girls starting to menstruate increased with age; (c) at all ages the variation of body weight at menarche was as large as that among non-menstruating girls: (d) only 41 per cent of girls started to menstruate at weights 48 +/- 5 kg; and (e) eleven of the 20 girls whose weight exceeded 48 kg at the age 10-5-11 years did not start to menstruate although 1-1-5 years had elapsed since they attained the \"critical\" weight. Although no direct body composition data are presented the behaviour of skinfold suggests that body composition is unlikely to be the primary trigger of menarche.", "contents": "Comments on the critical metabolic mass and the age of menarche. Data from Frisch and Revelle (1971) and Frisch et al. (1973) are used to show that some of their biological conclusions relating body composition to age at menarche follow directly from arithmetical operations on the two observed items of information: weight and height. This emphasizes the dangers of drawing biological conclusions from derived, as opposed to observed, data. The hypothesis that an age-unrelated critical body weight triggers off menarche is examined in relation to preliminary data from a longitudinal study of adolescent girls. It is unacceptable because: (a) mean weights at menarche showed an upward trend with increasing age; (b) for given body weights the proportion of girls starting to menstruate increased with age; (c) at all ages the variation of body weight at menarche was as large as that among non-menstruating girls: (d) only 41 per cent of girls started to menstruate at weights 48 +/- 5 kg; and (e) eleven of the 20 girls whose weight exceeded 48 kg at the age 10-5-11 years did not start to menstruate although 1-1-5 years had elapsed since they attained the \"critical\" weight. Although no direct body composition data are presented the behaviour of skinfold suggests that body composition is unlikely to be the primary trigger of menarche."} {"id": "PMID:1275433", "title": "Variation in upper arm length and forarm length in normal British girls: photogrammetric standards.", "content": "A photographic measuring technique has been used to study the lengths of the upper arm and forearm in normal British girls. The data are presented graphically, and show: 1. Ellipses which include 97 per cent of normal subjects when upper arm length is plotted against forearm length. 2. Variation of upper arm length and forearm length according to age. 3. Variation of upper arm length in relation to forearm length, irrespective of age. 4. Variation of upper arm length and forearm length in relation to sitting height, irrespective of age. The charts collectively provide a means of defining the exact nature of abnormalities of growth in the arms or of differences between populations. They provide a new aid to the classification of disorders involving abnormal growth of the arms.", "contents": "Variation in upper arm length and forarm length in normal British girls: photogrammetric standards. A photographic measuring technique has been used to study the lengths of the upper arm and forearm in normal British girls. The data are presented graphically, and show: 1. Ellipses which include 97 per cent of normal subjects when upper arm length is plotted against forearm length. 2. Variation of upper arm length and forearm length according to age. 3. Variation of upper arm length in relation to forearm length, irrespective of age. 4. Variation of upper arm length and forearm length in relation to sitting height, irrespective of age. The charts collectively provide a means of defining the exact nature of abnormalities of growth in the arms or of differences between populations. They provide a new aid to the classification of disorders involving abnormal growth of the arms."} {"id": "PMID:1275434", "title": "Day-to-day variation in body weights of children.", "content": "Day-to-day fluctuations in the body weights on five consecutive days of 54 boys and 50 girls aged between 2 and 6 years were measured. The standard deviation of the body weights over this period were of the order of +/- 0-2 kg in boys and girls. On the basis of these findings, it is suggested that only loss or gain in body weights of more than twice this amount should be taken as indicative of real change.", "contents": "Day-to-day variation in body weights of children. Day-to-day fluctuations in the body weights on five consecutive days of 54 boys and 50 girls aged between 2 and 6 years were measured. The standard deviation of the body weights over this period were of the order of +/- 0-2 kg in boys and girls. On the basis of these findings, it is suggested that only loss or gain in body weights of more than twice this amount should be taken as indicative of real change."} {"id": "PMID:1275435", "title": "The adolescent growth spurt of boys and girls of the Harpenden growth study.", "content": "Logistic curves have been fitted to the growth during puberty of the 55 boys and 35 girls of the Harpenden Growth Study who were measured every three months during puberty and thereafter until growth ceased. Very good fits were obtained for stature, sitting height, subischial leg length, biacromial and bi-iliac diameters from approximately six months after the beginning of the adolescent spurt. This beginning, called \"take-off\", was determined graphically as the point of minimum velocity. The total height gained from take-off point to cessation of growth averaged 28 cm in boys and 25 cm in girls with standard deviations of about 4 cm. The adult sex difference in height was due much more to the later take-off in boys than to a greater male adolescent spurt. A sex difference in the spurt occurred in sitting height but not in leg length. Mean-constant curves for the four measurements are presented. In each measurement size at take-off and total adolescent gain were nearly independent, the average correlation coefficient being --0-2. The correlations between adolescent gains in different measurements averaged only 0-47, and between peak velocities of different measurements only 0-27. This implies considerable shape change at adolescence. In contrast the average correlation between ages at which the peak velocities were reached was 0-87. Ages at take-off, at peak velocity, and at menarche were independent of mature size, though correlated with percentage of adult size reached at the ages in question, a measure of somatic maturity. Relationships with the development of breasts, pubic hair and genitalia were examined; ages at take-off and at peak velocity correlated to the extent of 0-6 to 0-8 with ages of B2 and PH2 but both these parameters and also peak velocities were uncorrelated with the rapidity with which sex characters developed.", "contents": "The adolescent growth spurt of boys and girls of the Harpenden growth study. Logistic curves have been fitted to the growth during puberty of the 55 boys and 35 girls of the Harpenden Growth Study who were measured every three months during puberty and thereafter until growth ceased. Very good fits were obtained for stature, sitting height, subischial leg length, biacromial and bi-iliac diameters from approximately six months after the beginning of the adolescent spurt. This beginning, called \"take-off\", was determined graphically as the point of minimum velocity. The total height gained from take-off point to cessation of growth averaged 28 cm in boys and 25 cm in girls with standard deviations of about 4 cm. The adult sex difference in height was due much more to the later take-off in boys than to a greater male adolescent spurt. A sex difference in the spurt occurred in sitting height but not in leg length. Mean-constant curves for the four measurements are presented. In each measurement size at take-off and total adolescent gain were nearly independent, the average correlation coefficient being --0-2. The correlations between adolescent gains in different measurements averaged only 0-47, and between peak velocities of different measurements only 0-27. This implies considerable shape change at adolescence. In contrast the average correlation between ages at which the peak velocities were reached was 0-87. Ages at take-off, at peak velocity, and at menarche were independent of mature size, though correlated with percentage of adult size reached at the ages in question, a measure of somatic maturity. Relationships with the development of breasts, pubic hair and genitalia were examined; ages at take-off and at peak velocity correlated to the extent of 0-6 to 0-8 with ages of B2 and PH2 but both these parameters and also peak velocities were uncorrelated with the rapidity with which sex characters developed."} {"id": "PMID:1275436", "title": "Blood polymorphism frequencies in the Sara Majingay of Chad.", "content": "Blood samples of 258 Sara Majingay of Ndila (Southern Chad) were analysed. Phenotype and allele frequencies are given for 22 polymorphisms. For each of these, the Majingay are compared to a number of other African populations. Then they are included in a set of 8 African populations between which multivariate distances for 25 alleles at 9 loci are computed. A two-dimensional representation is derived from the matrix of distances, and is discussed. It bears the stamp of gene flow in central Ethiopia, where an Arab admixture is evident, and in Southern Africa, where a reciprocal gene flow has marked the gene pools of Khoisan and Bantu speakers to a varying degree. The Majingay stand relatively near to the Bedik, another population of West-Central Africa. The non-Arab or non-Khoisan components of the gene pool of the other populations do not seem to differ largely from the gene pools of the West-Central African populations.", "contents": "Blood polymorphism frequencies in the Sara Majingay of Chad. Blood samples of 258 Sara Majingay of Ndila (Southern Chad) were analysed. Phenotype and allele frequencies are given for 22 polymorphisms. For each of these, the Majingay are compared to a number of other African populations. Then they are included in a set of 8 African populations between which multivariate distances for 25 alleles at 9 loci are computed. A two-dimensional representation is derived from the matrix of distances, and is discussed. It bears the stamp of gene flow in central Ethiopia, where an Arab admixture is evident, and in Southern Africa, where a reciprocal gene flow has marked the gene pools of Khoisan and Bantu speakers to a varying degree. The Majingay stand relatively near to the Bedik, another population of West-Central Africa. The non-Arab or non-Khoisan components of the gene pool of the other populations do not seem to differ largely from the gene pools of the West-Central African populations."} {"id": "PMID:1275437", "title": "Maximum aerobic power and physical dimensions of children.", "content": "Age, height, mass, fat-free mass and vital capacity were used as predictors of maximum aerobic power (VO2 max). The variables were cast in linear form by logarithmic transfomation and submitted to multiple regression analysis. Results indicate VO2 max as a power function of age, height and mass in 50 untrained boys aged 7 to 13 years. In this group the relationship between VO2 max and body mass may be expressed by the equation Y=0.076X0.88 (r=0.92, P <0.01). Age, height and mass together accounted for 89 per cent of the variance in VO2 max (R=0.94, P <0.01). In 30 girl swimmers and in 14 young boys during 22 months of running training, VO2 max was proportional to body mass and indicated greater maximum aerobic power for their size and age. In normally growing children, VO2 max appears to increase more slowly than body mass. Children subjected to aerobic training evidently maintain VO2 max in proportion to their increasing mass throughout adolescence.", "contents": "Maximum aerobic power and physical dimensions of children. Age, height, mass, fat-free mass and vital capacity were used as predictors of maximum aerobic power (VO2 max). The variables were cast in linear form by logarithmic transfomation and submitted to multiple regression analysis. Results indicate VO2 max as a power function of age, height and mass in 50 untrained boys aged 7 to 13 years. In this group the relationship between VO2 max and body mass may be expressed by the equation Y=0.076X0.88 (r=0.92, P <0.01). Age, height and mass together accounted for 89 per cent of the variance in VO2 max (R=0.94, P <0.01). In 30 girl swimmers and in 14 young boys during 22 months of running training, VO2 max was proportional to body mass and indicated greater maximum aerobic power for their size and age. In normally growing children, VO2 max appears to increase more slowly than body mass. Children subjected to aerobic training evidently maintain VO2 max in proportion to their increasing mass throughout adolescence."} {"id": "PMID:1275438", "title": "Skeletal maturation of children in Okinawa.", "content": "A radiological investigation of 115 boys and 149 girls aged 7-15 years on Okinawa Island was undertaken. The skeletal maturation of the hand and wrist was compared with that in Tokyo and Sapporo. For assessing skeletal maturity, the Tanner-Whitehouse-1 (1962) and Kimura (1972) methods were used. The children of Okinawa were somewhat retarded skeletally compared to those of Tokyo in early childhood. However, they matured more rapidly in childhood and at adolescence than children in Tokyo and Sapporo. These facts seem to agree well with the results from the physical measurements.", "contents": "Skeletal maturation of children in Okinawa. A radiological investigation of 115 boys and 149 girls aged 7-15 years on Okinawa Island was undertaken. The skeletal maturation of the hand and wrist was compared with that in Tokyo and Sapporo. For assessing skeletal maturity, the Tanner-Whitehouse-1 (1962) and Kimura (1972) methods were used. The children of Okinawa were somewhat retarded skeletally compared to those of Tokyo in early childhood. However, they matured more rapidly in childhood and at adolescence than children in Tokyo and Sapporo. These facts seem to agree well with the results from the physical measurements."} {"id": "PMID:1275439", "title": "The relationship of kyphosis to the shape of vertebral bodies.", "content": "An index which measures the wedge deformity of vertebral bodies in lateral chest radiographs in older people was calculated by dividing the sum of the vertical anterior heights of the lower six thoracic vertebral bodies and discs by the corresponding sum of vertical posterior heights. This index increased with increasing age in a similar manner in men and in women, in contradistinction to an index measuring kyphosis in which the age effect was greater in women. The index of wedging explained 42 per cent and 48 per cent of the variation in kyphosis in men and in women respectively. Additional effects due to age, detected in women only, added a further 4 per cent to the explained variation and may be due to ageing of soft tissues.", "contents": "The relationship of kyphosis to the shape of vertebral bodies. An index which measures the wedge deformity of vertebral bodies in lateral chest radiographs in older people was calculated by dividing the sum of the vertical anterior heights of the lower six thoracic vertebral bodies and discs by the corresponding sum of vertical posterior heights. This index increased with increasing age in a similar manner in men and in women, in contradistinction to an index measuring kyphosis in which the age effect was greater in women. The index of wedging explained 42 per cent and 48 per cent of the variation in kyphosis in men and in women respectively. Additional effects due to age, detected in women only, added a further 4 per cent to the explained variation and may be due to ageing of soft tissues."} {"id": "PMID:1275440", "title": "A longitudinal study of the growth of trunk surface area measured by planimeter on standard somatotype photographs.", "content": "Thoracic and abdominal surface areas have been measured by planimeter on 340 photogrammetric somatotype photographs of 15 boys of the Harpenden Growth Study followed at regular intervals from 3 to 20 years of age. Mean distance and velocity curves are given, estimated by Patterson's method for extracting maximum information from mixed longitudinal data. Both areas showed a marked adolescent growth spurt with the age at peak coinciding with the age of peak height velocity of the same children. The correlation coefficients between thorax and abdominal surface areas rose from an average of about 0-3 at ages 5-8 to 0-5 at ages 9-12 and 0-7 at ages 13-19. Trunk index (thorax/abdomen area) fell gradually with age from 5 to 9 and thereafter remained constant.", "contents": "A longitudinal study of the growth of trunk surface area measured by planimeter on standard somatotype photographs. Thoracic and abdominal surface areas have been measured by planimeter on 340 photogrammetric somatotype photographs of 15 boys of the Harpenden Growth Study followed at regular intervals from 3 to 20 years of age. Mean distance and velocity curves are given, estimated by Patterson's method for extracting maximum information from mixed longitudinal data. Both areas showed a marked adolescent growth spurt with the age at peak coinciding with the age of peak height velocity of the same children. The correlation coefficients between thorax and abdominal surface areas rose from an average of about 0-3 at ages 5-8 to 0-5 at ages 9-12 and 0-7 at ages 13-19. Trunk index (thorax/abdomen area) fell gradually with age from 5 to 9 and thereafter remained constant."} {"id": "PMID:1275441", "title": "Prevalence of dental caries of Chinese in Liverpool.", "content": "The dental caries prevalence of adult Chinese immigrants in the Liverpool area is considerably lower than that of the native British. This is in contrast to Chinese children born in the U.K. who appear to have a higher prevalence compared to the same age group of British children.", "contents": "Prevalence of dental caries of Chinese in Liverpool. The dental caries prevalence of adult Chinese immigrants in the Liverpool area is considerably lower than that of the native British. This is in contrast to Chinese children born in the U.K. who appear to have a higher prevalence compared to the same age group of British children."} {"id": "PMID:1275442", "title": "Enolase: human tissue distribution and evidence for three different loci.", "content": "Four different cellogel electrophoretic patterns of enolase were found in human tissue extracts. They consisted of: (A) one strongly stained band (I) and two minor bands (II and III) found in haemolysates, white cell, skin fibroblast and kidney extracts; (B) a three-banded pattern in brain resembling that of haemolysates except for heavier concentrations of bands II and III; (C) a single component corresponding to band I, found in liver, heart, intestine spleen and placenta; (D) a single band with slightly faster mobility than band I, found in adult muscle extracts. The haemolysate of an individual with the heterozygous ENO1/ENO2 genotype had a triple banded pattern replacing band I, a double-banded pattern replacing band II and a single weakly staining band III. This finding, as well as the results of dissociation and recombination experiments, supports the hypothesis that the enzyme is a dimer formed by random interaction of two polypeptide chains (alpha and beta) synthesized by two independent gene loci (ENO1 and ENO2). Evidence for a third locus, ENO3, is supplied by the electrophoretic pattern of muscle extracts.", "contents": "Enolase: human tissue distribution and evidence for three different loci. Four different cellogel electrophoretic patterns of enolase were found in human tissue extracts. They consisted of: (A) one strongly stained band (I) and two minor bands (II and III) found in haemolysates, white cell, skin fibroblast and kidney extracts; (B) a three-banded pattern in brain resembling that of haemolysates except for heavier concentrations of bands II and III; (C) a single component corresponding to band I, found in liver, heart, intestine spleen and placenta; (D) a single band with slightly faster mobility than band I, found in adult muscle extracts. The haemolysate of an individual with the heterozygous ENO1/ENO2 genotype had a triple banded pattern replacing band I, a double-banded pattern replacing band II and a single weakly staining band III. This finding, as well as the results of dissociation and recombination experiments, supports the hypothesis that the enzyme is a dimer formed by random interaction of two polypeptide chains (alpha and beta) synthesized by two independent gene loci (ENO1 and ENO2). Evidence for a third locus, ENO3, is supplied by the electrophoretic pattern of muscle extracts."} {"id": "PMID:1275443", "title": "Human alcohol dehydrogenase ADH1, ADH2 and ADH3 loci in a mixed population of Bahia, Brazil.", "content": "1. The three structural gene loci of human alcohol dehydrogenase have been studied in liver, jejunum and lung from 300 newborns in a triracially mixed population of Bahia, Brazil. 2. The frequency of the ADH23 allele was 0-1392, suggesting that the ADH23 allele is less frequent in Negroes. 3. A new ADH2 variant was identified. The electrophoretic pattern was interpreted as due to a new allele which is provisionally called ADH2Bahia. 4. By electrophoretic classification the 'atypical' variant was found in 2-8% of the sample. A question is raised regarding the ancestral origin of the 'atypical' variant in the population. Because this variant is common in Japanese it may have reached the present day population of Bahia through their American Indian ancestors. 5. Subjective estimation of the proportions of beta chains by giving scores to the liver isozymes alphaalpha, alphabeta and betabeta showed a clear relationship between the fetal weight and the beta chain activity. 6. The proportion of beta chains in the liver is significantly less when there is no enzyme activity in the lung, indicating some synchronous 'turning on' mechanism for alcohol dehydrogenase synthesis in both tissues.", "contents": "Human alcohol dehydrogenase ADH1, ADH2 and ADH3 loci in a mixed population of Bahia, Brazil. 1. The three structural gene loci of human alcohol dehydrogenase have been studied in liver, jejunum and lung from 300 newborns in a triracially mixed population of Bahia, Brazil. 2. The frequency of the ADH23 allele was 0-1392, suggesting that the ADH23 allele is less frequent in Negroes. 3. A new ADH2 variant was identified. The electrophoretic pattern was interpreted as due to a new allele which is provisionally called ADH2Bahia. 4. By electrophoretic classification the 'atypical' variant was found in 2-8% of the sample. A question is raised regarding the ancestral origin of the 'atypical' variant in the population. Because this variant is common in Japanese it may have reached the present day population of Bahia through their American Indian ancestors. 5. Subjective estimation of the proportions of beta chains by giving scores to the liver isozymes alphaalpha, alphabeta and betabeta showed a clear relationship between the fetal weight and the beta chain activity. 6. The proportion of beta chains in the liver is significantly less when there is no enzyme activity in the lung, indicating some synchronous 'turning on' mechanism for alcohol dehydrogenase synthesis in both tissues."} {"id": "PMID:1275444", "title": "Genetic markers in trisomies 13 and 18.", "content": "Data on centromeric linkage for trisomies 13 and 18 are presented. There is no substantial evidence that any of these loci studied are on either chromosome. There is weak evidence relating the locus defining the Kidd groups to chromosome 18.", "contents": "Genetic markers in trisomies 13 and 18. Data on centromeric linkage for trisomies 13 and 18 are presented. There is no substantial evidence that any of these loci studied are on either chromosome. There is weak evidence relating the locus defining the Kidd groups to chromosome 18."} {"id": "PMID:1275445", "title": "Population structure of Barra (Outer Hebrides).", "content": "Historical demography, surname concordance (isonymy), migration, and genealogy give a consistent description of population structure. The census size has averaged about 1400 over the last five centuries. Conjoined with an effective migration rate of 3-05 per generation as estimated by three different methods, this gives an evolutionary size of 638, random kinship of 0-008 and inbreeding of 0-007 relative to the rest of Britain. The population structure of Barra is similar to other British isolates in the recent past, but an order of magnitude less inbred than slash-and-burn agriculturalists and Pacific Islanders. Some consequences for rare genes and polymorphisms are discussed.", "contents": "Population structure of Barra (Outer Hebrides). Historical demography, surname concordance (isonymy), migration, and genealogy give a consistent description of population structure. The census size has averaged about 1400 over the last five centuries. Conjoined with an effective migration rate of 3-05 per generation as estimated by three different methods, this gives an evolutionary size of 638, random kinship of 0-008 and inbreeding of 0-007 relative to the rest of Britain. The population structure of Barra is similar to other British isolates in the recent past, but an order of magnitude less inbred than slash-and-burn agriculturalists and Pacific Islanders. Some consequences for rare genes and polymorphisms are discussed."} {"id": "PMID:1275446", "title": "Selection of biochemically variant clones of human lymphoid cells.", "content": "Two established clones of human lymphoid cells, Raji and P3HRI, could be cloned in semi-solid agarose-containing medium at high efficiency. Several other human lymphoid cell lines examined cloned poorly if at all under these conditions. Variant clones of Raji and P3HRI resistant to 6-thioguanine, and in the case of Raji also to either 8-azaadenine or 5-bromo-2'-deoxyuridine, were selected and characterized.", "contents": "Selection of biochemically variant clones of human lymphoid cells. Two established clones of human lymphoid cells, Raji and P3HRI, could be cloned in semi-solid agarose-containing medium at high efficiency. Several other human lymphoid cell lines examined cloned poorly if at all under these conditions. Variant clones of Raji and P3HRI resistant to 6-thioguanine, and in the case of Raji also to either 8-azaadenine or 5-bromo-2'-deoxyuridine, were selected and characterized."} {"id": "PMID:1275447", "title": "Bernstein's and gene-counting methods in generalized ABO-like systems.", "content": "Although the simple and adjusted Bernstein's methods are fully efficient for m=2 and m=3 (ABO system) respectively, their efficiency declines for larger values of m. For m greater than or equal to 4, the adjusted or modified Bernstein's method with a single counting iteration leads to a nearly efficient estimator. A single degree of freedom chi-square test of the Hardy-Weinberg law for all m is derived. Some findings on the statistical efficiency of typing various numbers of antigens are given. All the results are illustrated in numerical examples.", "contents": "Bernstein's and gene-counting methods in generalized ABO-like systems. Although the simple and adjusted Bernstein's methods are fully efficient for m=2 and m=3 (ABO system) respectively, their efficiency declines for larger values of m. For m greater than or equal to 4, the adjusted or modified Bernstein's method with a single counting iteration leads to a nearly efficient estimator. A single degree of freedom chi-square test of the Hardy-Weinberg law for all m is derived. Some findings on the statistical efficiency of typing various numbers of antigens are given. All the results are illustrated in numerical examples."} {"id": "PMID:1275449", "title": "[Study of the chemical makeup of the mycelium from an active strain of Act. rimosus and from an inactive mutant in relaiton to oxytetracycline biosynthesis].", "content": "Chemical composition of the mycelium of the active and inactive mutants of Act. rimosus grown under conditions favourable for oxytetracycline biosynthesis on the starch or maltose medium and under favourable conditions on the glucose medium was studied. It was shown that according to its chemical composition the above strains did not practically differ. When grown on the starch medium the mycelium of both strains contained great amounts of carbohydrates and comparatively small amounts of nucleic acids and nitrogen. Replacement of starch in the medium by glucose or maltose induced significant changes in the mycelium composition: the synthesis of intracellular polysaccharides was markedly suppressed and the synthesis of nucleic acids and nitrogen containing compounds increased. RNA was the main nucleic acid in both strains on starch and glucose media. The content of DNA was low and did not practically change. The mycelium of both strains contained small amounts of lipids which did not significantly change during the process of cultivation and did not correlate with the antibiotic activity.", "contents": "[Study of the chemical makeup of the mycelium from an active strain of Act. rimosus and from an inactive mutant in relaiton to oxytetracycline biosynthesis]. Chemical composition of the mycelium of the active and inactive mutants of Act. rimosus grown under conditions favourable for oxytetracycline biosynthesis on the starch or maltose medium and under favourable conditions on the glucose medium was studied. It was shown that according to its chemical composition the above strains did not practically differ. When grown on the starch medium the mycelium of both strains contained great amounts of carbohydrates and comparatively small amounts of nucleic acids and nitrogen. Replacement of starch in the medium by glucose or maltose induced significant changes in the mycelium composition: the synthesis of intracellular polysaccharides was markedly suppressed and the synthesis of nucleic acids and nitrogen containing compounds increased. RNA was the main nucleic acid in both strains on starch and glucose media. The content of DNA was low and did not practically change. The mycelium of both strains contained small amounts of lipids which did not significantly change during the process of cultivation and did not correlate with the antibiotic activity."} {"id": "PMID:1275450", "title": "[Isolation and study of the physicochemical properties of the partial acid hydrolysis products of the aglycone actinoidin].", "content": "Two new fragments, i.e. products I and II were found in the process of studying the products of acid hydrolysis of actinoidin aglycone. Both compounds were isolated in the form of homogenous preparations by the method of ion exchange chromatography on cellulose KM. Their physico-chemical properties and element composition were studied. It was found that product I was phenylalanine dipeptide (Phe) and oxyaromatic triamiotricarboxylic compound (Y) not described earlier, while product II was tripeptide including diaminodicarboxylic actinoidinic amino acid (B) in addition to phenylalanine and fragment Y.", "contents": "[Isolation and study of the physicochemical properties of the partial acid hydrolysis products of the aglycone actinoidin]. Two new fragments, i.e. products I and II were found in the process of studying the products of acid hydrolysis of actinoidin aglycone. Both compounds were isolated in the form of homogenous preparations by the method of ion exchange chromatography on cellulose KM. Their physico-chemical properties and element composition were studied. It was found that product I was phenylalanine dipeptide (Phe) and oxyaromatic triamiotricarboxylic compound (Y) not described earlier, while product II was tripeptide including diaminodicarboxylic actinoidinic amino acid (B) in addition to phenylalanine and fragment Y."} {"id": "PMID:1275451", "title": "[Study of the dynamics of n-propyl alcohol in an Act. erythreus culture during the biosynthesis of erythromycin using a gas-liquid chromatographic method].", "content": "The effect of n-propyl alcohol on biosynthesis of erythromycin and the dynamics of the precursor consumption were studied with the method of gas-liquid chromatography. It was shown that neither the optimal concentration of the precursor, nor its stimulating effect on different media correlated. n-Propyl alcohol was used not only for the antibiotic biosynthesis but also according to other metabolic path-ways and in addition its evaporation from the medium was registered. During the first period of the fermentation n-propyl alcohol suppressed the antibiotic biosynthesis.", "contents": "[Study of the dynamics of n-propyl alcohol in an Act. erythreus culture during the biosynthesis of erythromycin using a gas-liquid chromatographic method]. The effect of n-propyl alcohol on biosynthesis of erythromycin and the dynamics of the precursor consumption were studied with the method of gas-liquid chromatography. It was shown that neither the optimal concentration of the precursor, nor its stimulating effect on different media correlated. n-Propyl alcohol was used not only for the antibiotic biosynthesis but also according to other metabolic path-ways and in addition its evaporation from the medium was registered. During the first period of the fermentation n-propyl alcohol suppressed the antibiotic biosynthesis."} {"id": "PMID:1275453", "title": "[New antibiotic, parvulomycin, produced by a culture of Actinomyces parvullus var. chromogenes var. nov].", "content": "Actinomycete LIA-O784 was isolated from a soil sample. By its morphological and cultural properties the isolate was close to Act. parvullus but differed from it in synthesis of melanoid pygment, thyrosinase, hydrogen sulphide and pronounced antifungal activity. The actinomycete was classified as a new variant and designated as Actinomyces parvullus var. chromogenes var. nov. The culture produced a new polyglycoside antibiotic named parvulomycin. The physico-chemical characteristics of the antibiotic is presented.", "contents": "[New antibiotic, parvulomycin, produced by a culture of Actinomyces parvullus var. chromogenes var. nov]. Actinomycete LIA-O784 was isolated from a soil sample. By its morphological and cultural properties the isolate was close to Act. parvullus but differed from it in synthesis of melanoid pygment, thyrosinase, hydrogen sulphide and pronounced antifungal activity. The actinomycete was classified as a new variant and designated as Actinomyces parvullus var. chromogenes var. nov. The culture produced a new polyglycoside antibiotic named parvulomycin. The physico-chemical characteristics of the antibiotic is presented."} {"id": "PMID:1275455", "title": "[Sensitivity of Mycoplasma hominis cultures isolated from clinical material to certain antibiotics].", "content": "Sensitivity to II antibiotics of 80 strains of M. hominis isolated from patients with various inflammatory processes of the urogenital tract was studied by the method of suppressing the metabolic activity. Inhibition of the arginine metabolism of mycoplasma was used as a test for determination of the growth suppression. All the strains tested were highly sensitive to tetracycline and lincomycin. Kanamycin and neomycin were less active against M. hominis. All the strains tested were resistant to erythromycin, oleandomycin, ristomycin, novobiocin and streptomycin. The inhibitory effect of tetracycline and lincomycin on M. hominis decreased by the 5th day.", "contents": "[Sensitivity of Mycoplasma hominis cultures isolated from clinical material to certain antibiotics]. Sensitivity to II antibiotics of 80 strains of M. hominis isolated from patients with various inflammatory processes of the urogenital tract was studied by the method of suppressing the metabolic activity. Inhibition of the arginine metabolism of mycoplasma was used as a test for determination of the growth suppression. All the strains tested were highly sensitive to tetracycline and lincomycin. Kanamycin and neomycin were less active against M. hominis. All the strains tested were resistant to erythromycin, oleandomycin, ristomycin, novobiocin and streptomycin. The inhibitory effect of tetracycline and lincomycin on M. hominis decreased by the 5th day."} {"id": "PMID:1275456", "title": "[Actinomyces streptomycini mutant blocked in streptidine biosynthesis].", "content": "Mutant 170 not capable of forming streptidine and streptomycin was obtained using chemical mutagenes. This mutant can produce streptomycin only with suplementation of exogenous streptidine. Experiment with labeled C14-streptidine showed its specific incorporation in streptidine moiety of streptomycin molecule.", "contents": "[Actinomyces streptomycini mutant blocked in streptidine biosynthesis]. Mutant 170 not capable of forming streptidine and streptomycin was obtained using chemical mutagenes. This mutant can produce streptomycin only with suplementation of exogenous streptidine. Experiment with labeled C14-streptidine showed its specific incorporation in streptidine moiety of streptomycin molecule."} {"id": "PMID:1275457", "title": "[Antibiotic interaction with proteolytic enzymes].", "content": "The effect of penicillin, tetracycline, aminoglucozide antibiotics and streptomycin on BAEE-esterase activity of trypsin was studied. It was found that benzylpenicillin in amounts of 50, 100 and 300 mg, ampicillin in an amount of 25 mg, methicillin in an amount of 12 mg and tetracycline in an amount of 2.5 mg as calculated per 1 mg of trypsin had no effect in vitro on the esterase activity of the enzyme. Neomycin, kanamycin and streptomycin in amounts of 5, 10, 100 or 300 mg per 1 mg of trypsin catalyzed splitting of BAEE by trypsin. When the antibiotics were added to the bile, its esterase activity increased. Preliminary intramuscular administration of trypsin and kanamycin to the rats had no effect on the ampicillin levels in the blood serum and brain and did not affect the permeability of the hemato-encephalic barrier as compared to the use of trypsin alone.", "contents": "[Antibiotic interaction with proteolytic enzymes]. The effect of penicillin, tetracycline, aminoglucozide antibiotics and streptomycin on BAEE-esterase activity of trypsin was studied. It was found that benzylpenicillin in amounts of 50, 100 and 300 mg, ampicillin in an amount of 25 mg, methicillin in an amount of 12 mg and tetracycline in an amount of 2.5 mg as calculated per 1 mg of trypsin had no effect in vitro on the esterase activity of the enzyme. Neomycin, kanamycin and streptomycin in amounts of 5, 10, 100 or 300 mg per 1 mg of trypsin catalyzed splitting of BAEE by trypsin. When the antibiotics were added to the bile, its esterase activity increased. Preliminary intramuscular administration of trypsin and kanamycin to the rats had no effect on the ampicillin levels in the blood serum and brain and did not affect the permeability of the hemato-encephalic barrier as compared to the use of trypsin alone."} {"id": "PMID:1275458", "title": "[Local use of neomycin. The histomorphological changes on the part of the neuroreceptor apparatus of the rabbit cornea].", "content": "The experimental histological studies with rabbits showed that neomycin in the form of 1 and 10 per cent solutions and ointments used for prolong periods of time affected the neuroreceptor apparatus of the animal cornea. It is not recommended to use 10 per cent solutions and ointments in the ophthalmological practice. Before using neomycin it is necessary to examine the cornea sensitivity and if it is lowered, the antibiotic should not be used.", "contents": "[Local use of neomycin. The histomorphological changes on the part of the neuroreceptor apparatus of the rabbit cornea]. The experimental histological studies with rabbits showed that neomycin in the form of 1 and 10 per cent solutions and ointments used for prolong periods of time affected the neuroreceptor apparatus of the animal cornea. It is not recommended to use 10 per cent solutions and ointments in the ophthalmological practice. Before using neomycin it is necessary to examine the cornea sensitivity and if it is lowered, the antibiotic should not be used."} {"id": "PMID:1275459", "title": "[Effect of population density on Actinomyces resistomycificus biosynthesis of heliomycin and resistoflavin].", "content": "Determination of heliomycin and resistoflavin contents in colonies of Act. resistomycilicus grown on pads with different density showed that the population density may be a factor controlling the level of the antibiotic biosynthesis by Act. resistomycificus and directing it along production of heliomycin or resistoflavin.", "contents": "[Effect of population density on Actinomyces resistomycificus biosynthesis of heliomycin and resistoflavin]. Determination of heliomycin and resistoflavin contents in colonies of Act. resistomycilicus grown on pads with different density showed that the population density may be a factor controlling the level of the antibiotic biosynthesis by Act. resistomycificus and directing it along production of heliomycin or resistoflavin."} {"id": "PMID:1275460", "title": "[Action of N-nitroso-N-methylbiuret on Penicillium nigricans Thom and the protective effect in UV irradiation].", "content": "N-Nitrozo-N-methylbiuret (NMB) in a concentration of 0.2% and exposition for 2,3,4 and 6 hours with the survival rate of the conidia of 4-25% induced slight morphological variation of the griseofulvin-producing organism and increased the variation rate with respect to the antibiotic production by 40-140%. Preliminary treatment of the conidia with NMB decreased the lethal effect of UV-rays approximately by 15-25 times. The protective range with respect to morphological variation was 10 times lower. With an increase in the toxicity of NMB its protective effect in irradiation with UV-light decreased.", "contents": "[Action of N-nitroso-N-methylbiuret on Penicillium nigricans Thom and the protective effect in UV irradiation]. N-Nitrozo-N-methylbiuret (NMB) in a concentration of 0.2% and exposition for 2,3,4 and 6 hours with the survival rate of the conidia of 4-25% induced slight morphological variation of the griseofulvin-producing organism and increased the variation rate with respect to the antibiotic production by 40-140%. Preliminary treatment of the conidia with NMB decreased the lethal effect of UV-rays approximately by 15-25 times. The protective range with respect to morphological variation was 10 times lower. With an increase in the toxicity of NMB its protective effect in irradiation with UV-light decreased."} {"id": "PMID:1275461", "title": "[Study of certain carbohydrate metabolism enzymes in an active oxytetracycline producer strain and in an inactive mutant in relation to antibiotic biosynthesis].", "content": "The activity of the glycolysis enzymes, i.e. aldolase and pyruvate decarboxylase and the enzymes of the pentose cycle, i.e. transketolase were investigated in the process of cultivation of an active strain and inactive mutant of Act. rimosus under conditions favourable for oxytetracycline biosynthesis on starch medium and under unfavourable conditions on glucose medium. It was shown that the aldolase and transketolase activity in the inactive mutant was higher on the starch medium as compared to the active strain, while the activity of pyruvate dekarboxylase was lower. The above difference between the both strains was preserved on the glucose medium and the activity of aldolase and transketolase in both strains increased, while the activity of pyruvate dekarboxylase remained at the same level.", "contents": "[Study of certain carbohydrate metabolism enzymes in an active oxytetracycline producer strain and in an inactive mutant in relation to antibiotic biosynthesis]. The activity of the glycolysis enzymes, i.e. aldolase and pyruvate decarboxylase and the enzymes of the pentose cycle, i.e. transketolase were investigated in the process of cultivation of an active strain and inactive mutant of Act. rimosus under conditions favourable for oxytetracycline biosynthesis on starch medium and under unfavourable conditions on glucose medium. It was shown that the aldolase and transketolase activity in the inactive mutant was higher on the starch medium as compared to the active strain, while the activity of pyruvate dekarboxylase was lower. The above difference between the both strains was preserved on the glucose medium and the activity of aldolase and transketolase in both strains increased, while the activity of pyruvate dekarboxylase remained at the same level."} {"id": "PMID:1275462", "title": "[Utilization of automatic systems for determining the biological activity of antibiotics by the agar diffusion method].", "content": "The Automatic Zone Analyzer AR-140 of Millipor intertech., inc. is an apparatus used for measurement of inhibition growth zones of test-microbes and estimation of antibiotic activity. The analyzer provides automatic registration of the data with high levels of accuracy and at least 99% reproducibility. The analyzer gives an effect in saving time as compared to the manual method by 5-7 times for the single-dose procedure and by 10-12 times for the three-dose procedure.", "contents": "[Utilization of automatic systems for determining the biological activity of antibiotics by the agar diffusion method]. The Automatic Zone Analyzer AR-140 of Millipor intertech., inc. is an apparatus used for measurement of inhibition growth zones of test-microbes and estimation of antibiotic activity. The analyzer provides automatic registration of the data with high levels of accuracy and at least 99% reproducibility. The analyzer gives an effect in saving time as compared to the manual method by 5-7 times for the single-dose procedure and by 10-12 times for the three-dose procedure."} {"id": "PMID:1275463", "title": "[Sensitivity to antibacterial preparations of the pathogenic staphylococci isolated from carriers].", "content": "After discontinuation of the use of antibiotics for sanation of the carriers of pathogenic staphylococci among the staff of a maternity unit, the number of the strains resistant to penicillin, streptomycin, chlortetracycline, tetracycline, levomycetin, erythromycin, monomycin and neomycin decreased 1.3, 2.9, 10,4.3,5.5,1.5,3.9 and 2.4 times respectively. The differences were statistically reliable. The causes of the antibiotic resistance decrease require further investigation.", "contents": "[Sensitivity to antibacterial preparations of the pathogenic staphylococci isolated from carriers]. After discontinuation of the use of antibiotics for sanation of the carriers of pathogenic staphylococci among the staff of a maternity unit, the number of the strains resistant to penicillin, streptomycin, chlortetracycline, tetracycline, levomycetin, erythromycin, monomycin and neomycin decreased 1.3, 2.9, 10,4.3,5.5,1.5,3.9 and 2.4 times respectively. The differences were statistically reliable. The causes of the antibiotic resistance decrease require further investigation."} {"id": "PMID:1275464", "title": "[Effect of some antibiotics on the resistance of white mice to staphylococcal toxin].", "content": "Penicillin and streptomycin in experimental staphylococcal intoxication had different effects on the disease depending on the period of their use. Penicillin injections prior to administration of the toxin increased significantly the resistance of the animals to it, while with the use of streptomycin there was only a tendency to its increase. The use of both antibiotics against the background of the intoxication had a reverse effect: there was a tendency to a decreased animal resistance to a greater extent with the use of streptomycin. The use of tetracycline hydrochloride had no effect on the animal resistance to the staphylococcal toxin.", "contents": "[Effect of some antibiotics on the resistance of white mice to staphylococcal toxin]. Penicillin and streptomycin in experimental staphylococcal intoxication had different effects on the disease depending on the period of their use. Penicillin injections prior to administration of the toxin increased significantly the resistance of the animals to it, while with the use of streptomycin there was only a tendency to its increase. The use of both antibiotics against the background of the intoxication had a reverse effect: there was a tendency to a decreased animal resistance to a greater extent with the use of streptomycin. The use of tetracycline hydrochloride had no effect on the animal resistance to the staphylococcal toxin."} {"id": "PMID:1275465", "title": "[Distribution and binding of oxytetracycline in the body of immunized animals].", "content": "Distribution and binding of oxytetracycline in immunized animals at various periods of immunogenesis (5, 10, 15, 20, 30 and 90 days after vaccination) were studied on rabbits, using dry live brucellosis vaccine, strain 19 as the antigen. The results of the study showed that immunological reconstruction of the macroorganism, its protective forces had a definite effect on the character of distribution, absorption and levels of oxytetracycline, as well as the processes of the antibiotic binding in the organism. The changes were indirect dependence on the immunogenesis periods: at the beginning of immunogenesis there was some increase in the antibiotic levels, as well as increased binding of the drug in the organs where reconstruction, activation and hyperplasia of the lymphoreticular cells occurred. During the productive phase of the antigen formation the antibiotic levels were 1,5-2 times lower, however, the processes of the antibiotic binding were more pronounced in the organs, where immunocompetent cells and antibodies were synthesized. During extinction of immunogenesis reduction of the initial antibiotic levels was recorded. Therefore, the changes directly depended on the periods of immunogenesis.", "contents": "[Distribution and binding of oxytetracycline in the body of immunized animals]. Distribution and binding of oxytetracycline in immunized animals at various periods of immunogenesis (5, 10, 15, 20, 30 and 90 days after vaccination) were studied on rabbits, using dry live brucellosis vaccine, strain 19 as the antigen. The results of the study showed that immunological reconstruction of the macroorganism, its protective forces had a definite effect on the character of distribution, absorption and levels of oxytetracycline, as well as the processes of the antibiotic binding in the organism. The changes were indirect dependence on the immunogenesis periods: at the beginning of immunogenesis there was some increase in the antibiotic levels, as well as increased binding of the drug in the organs where reconstruction, activation and hyperplasia of the lymphoreticular cells occurred. During the productive phase of the antigen formation the antibiotic levels were 1,5-2 times lower, however, the processes of the antibiotic binding were more pronounced in the organs, where immunocompetent cells and antibodies were synthesized. During extinction of immunogenesis reduction of the initial antibiotic levels was recorded. Therefore, the changes directly depended on the periods of immunogenesis."} {"id": "PMID:1275466", "title": "[Differentiation of the degree of bioavailability of peroral drug forms of tetracycline hydrochloride in experiments on laboratory animals].", "content": "Difference in the levels of bioavailability of 4 types of tetracycline hydrochloride tablets was shown on rabbits and guinea pigs. The rates of the antibiotic absorption into the blood of the laboratory animals and volunteers were the same. Relation between the rate of disintegration of various types of tablets of tetracycline hydrochloride and the antibiotic blood levels in the rabbits after administration of the same tablets was found.", "contents": "[Differentiation of the degree of bioavailability of peroral drug forms of tetracycline hydrochloride in experiments on laboratory animals]. Difference in the levels of bioavailability of 4 types of tetracycline hydrochloride tablets was shown on rabbits and guinea pigs. The rates of the antibiotic absorption into the blood of the laboratory animals and volunteers were the same. Relation between the rate of disintegration of various types of tablets of tetracycline hydrochloride and the antibiotic blood levels in the rabbits after administration of the same tablets was found."} {"id": "PMID:1275467", "title": "[Antibiotic penetration through the blood-brain barrier in rats and the effect on this process of proteolytic enzymes].", "content": "Penetration of penicillin, ampicillin, oxacillin, tetracycline, streptomycin and gentamycin through the hemato-encephalic barrier in rats and effect of proteolytic enzymes on the above process were studied comparatively. The levels of penetration to the brain were highest for ampicillin, then followed penicillin, tetracycline, oxacillin, streptomycin and gentamycin. Preliminary intramuscular administration of trypsin and chimotrypsin (10 mg/kg) to the animals had no effect on permeability of the hemato-encephalic barrier for the antibiotics tested, except penicillin. Higher levels of the antibiotics in the brain tissue may be explained by higher antibiotic blood levels under the effect of proteolytic enzymes.", "contents": "[Antibiotic penetration through the blood-brain barrier in rats and the effect on this process of proteolytic enzymes]. Penetration of penicillin, ampicillin, oxacillin, tetracycline, streptomycin and gentamycin through the hemato-encephalic barrier in rats and effect of proteolytic enzymes on the above process were studied comparatively. The levels of penetration to the brain were highest for ampicillin, then followed penicillin, tetracycline, oxacillin, streptomycin and gentamycin. Preliminary intramuscular administration of trypsin and chimotrypsin (10 mg/kg) to the animals had no effect on permeability of the hemato-encephalic barrier for the antibiotics tested, except penicillin. Higher levels of the antibiotics in the brain tissue may be explained by higher antibiotic blood levels under the effect of proteolytic enzymes."} {"id": "PMID:1275468", "title": "[Study of the immunological properties of Actinomyces rimosus ribonuclease].", "content": "The immunological properties of ribonucleases from Act. rimosus were studied in comparison with RNA-ase from the cattle pancreas. The activity of anti-RNA-ase immune sera were determined by the method of specific neutralization of the effect of the above exzymes. The results of the study showed that with the use of homological RNA-ases as the antigens, the maximum level of enzymatic activity neutralization by the immune sera ranged within 70 to 90% and the capacity for induction of specific antibody production expressed in the serum titer was somewhat lower in the actinomycete RNA-ase than in the pancreatic one. When heterological antigens were used, neutralization of the RNA-ase effect by the immune sera was either not detectable or very low which is indicative of the antigenic differences in the actinomycete and pancreatic RNA-ases.", "contents": "[Study of the immunological properties of Actinomyces rimosus ribonuclease]. The immunological properties of ribonucleases from Act. rimosus were studied in comparison with RNA-ase from the cattle pancreas. The activity of anti-RNA-ase immune sera were determined by the method of specific neutralization of the effect of the above exzymes. The results of the study showed that with the use of homological RNA-ases as the antigens, the maximum level of enzymatic activity neutralization by the immune sera ranged within 70 to 90% and the capacity for induction of specific antibody production expressed in the serum titer was somewhat lower in the actinomycete RNA-ase than in the pancreatic one. When heterological antigens were used, neutralization of the RNA-ase effect by the immune sera was either not detectable or very low which is indicative of the antigenic differences in the actinomycete and pancreatic RNA-ases."} {"id": "PMID:1275469", "title": "[Study using the probit-analysis method of the process of increasing resistance to dipin and bruneomycin in Fisher L-5178 lymphadenosis cells in experiments on animals].", "content": "The study of the process of resistance induction in the cells of lymphadenosis to dipin (subline L-5178/D) and bruneomycin (subline L-5178/B) showed that with increasing of the resistance relation between the drug dose and the antitumor effect gradually faded. It was found that only at the first stages of induction of the resistance increase may be found by comparison of values ED50 and ED70 of the lymphadenosis sensitive strain and its resistant sublines. The probit-analysis method provided registration of the resistance increase also at later stages. In this case the resistance level may be estimated by the slope of the dose-response curve.", "contents": "[Study using the probit-analysis method of the process of increasing resistance to dipin and bruneomycin in Fisher L-5178 lymphadenosis cells in experiments on animals]. The study of the process of resistance induction in the cells of lymphadenosis to dipin (subline L-5178/D) and bruneomycin (subline L-5178/B) showed that with increasing of the resistance relation between the drug dose and the antitumor effect gradually faded. It was found that only at the first stages of induction of the resistance increase may be found by comparison of values ED50 and ED70 of the lymphadenosis sensitive strain and its resistant sublines. The probit-analysis method provided registration of the resistance increase also at later stages. In this case the resistance level may be estimated by the slope of the dose-response curve."} {"id": "PMID:1275470", "title": "[Primary cell cultures of leukosis P-388 as a possible model for the screening of antitumor substances].", "content": "A substrain of the ascitic leucosis P-388 was obtained as a result of interchanging passages of P-388 leucosis cells in the primary cultures and abdominal cavity of mice. The tumor cells of the ascitic leucosis P-388 multiplied in the primary suspended culutres as well as in vivo. The substrain lost its hemorrhagic properties. The content of DNA and RNA in the primary cultures of P-388 doubled every 16-18 hours and the number of the cells doubled every 24-26 hours. The cells of the adapted substrain of P-388 grew also in the semiliquid agarized medium forming compact colonies by the 4th-5th day of cultivation. The primary suspended cultures of P-388 were highly sensitive to cytostatics and in particular to vinblastin and kolchamine (alkaloids). In this connection they were recommended for prescreening antitumor compounds.", "contents": "[Primary cell cultures of leukosis P-388 as a possible model for the screening of antitumor substances]. A substrain of the ascitic leucosis P-388 was obtained as a result of interchanging passages of P-388 leucosis cells in the primary cultures and abdominal cavity of mice. The tumor cells of the ascitic leucosis P-388 multiplied in the primary suspended culutres as well as in vivo. The substrain lost its hemorrhagic properties. The content of DNA and RNA in the primary cultures of P-388 doubled every 16-18 hours and the number of the cells doubled every 24-26 hours. The cells of the adapted substrain of P-388 grew also in the semiliquid agarized medium forming compact colonies by the 4th-5th day of cultivation. The primary suspended cultures of P-388 were highly sensitive to cytostatics and in particular to vinblastin and kolchamine (alkaloids). In this connection they were recommended for prescreening antitumor compounds."} {"id": "PMID:1275471", "title": "[Experimental study of the action of the antitumor antibiotic reumycin on the macroorganism].", "content": "The side effect of reumycin, an antitumor antibiotic was studied experimentally. The average lethal dose for mice and rats on intravenous administration of the drug was 45.5 and 42.2 mg/kg respectively. When reumycin was administered to rats and dogs for prolong periods of time, an increase in the levels of total protein, urea nitrogen and inorganic phosphorus in the blood was observed, while the levels of hemoglobin and thrombocyte counts decreased, the process of the blood coagulation being slower. The changes in the ECG were similar to those observed in the myocardium dystrophy. The morphological changes in the organs were characterized by perivascular edema, swelling of the vessel walls and edema of the interstitial tissues.", "contents": "[Experimental study of the action of the antitumor antibiotic reumycin on the macroorganism]. The side effect of reumycin, an antitumor antibiotic was studied experimentally. The average lethal dose for mice and rats on intravenous administration of the drug was 45.5 and 42.2 mg/kg respectively. When reumycin was administered to rats and dogs for prolong periods of time, an increase in the levels of total protein, urea nitrogen and inorganic phosphorus in the blood was observed, while the levels of hemoglobin and thrombocyte counts decreased, the process of the blood coagulation being slower. The changes in the ECG were similar to those observed in the myocardium dystrophy. The morphological changes in the organs were characterized by perivascular edema, swelling of the vessel walls and edema of the interstitial tissues."} {"id": "PMID:1275472", "title": "[Purification of antibiotic solutions of finely dispersed admixtures].", "content": "A possibility of complete separation of fine disperse admixtures from antibiotic fermentation broth filtrates by filtration with the use of special additives was shown. The purity of the filtrates and filtration rate depended on the procedure of addition, amount and average size of the particles of the filtration material.", "contents": "[Purification of antibiotic solutions of finely dispersed admixtures]. A possibility of complete separation of fine disperse admixtures from antibiotic fermentation broth filtrates by filtration with the use of special additives was shown. The purity of the filtrates and filtration rate depended on the procedure of addition, amount and average size of the particles of the filtration material."} {"id": "PMID:1275473", "title": "[Use of a rotation chart for studying the flocculation of admixtures in native solutions].", "content": "The process of admixture flocculation in fermentation broth filtrates of penicillin was studied experimentally according to the schemes of rotatabel planning of the 2nd order. Equations describing the effect of the main factors on the process were worked out and the main effects of the pair interactions were found.", "contents": "[Use of a rotation chart for studying the flocculation of admixtures in native solutions]. The process of admixture flocculation in fermentation broth filtrates of penicillin was studied experimentally according to the schemes of rotatabel planning of the 2nd order. Equations describing the effect of the main factors on the process were worked out and the main effects of the pair interactions were found."} {"id": "PMID:1275474", "title": "[Lysozyme activity in the leukocytes and blood serum of white rats administered massive doses of penicillin preparations].", "content": "Activity of lysozyme in the blood serum and leucocytes was determined. The experiments were carried out on albino unbred rats weighing 170 to 200 gm. Benzylpenicillin and oxacillin were administered intramuscularly in doses of 500000 Units/kg or 20000 gamma/kg once every 24 hours for 2, 4 and 6 days. The activity of lysozyme was determined by the turbidimetric and agar-diffusion methods. It was found that the activity of lysozyme in the leucocytes increased by the 5th day accompanied by a simultaneous decrease in its level in the serum followed by reaching the initial values. The data are indicative of the fact that the use of antibiotics in mega-doses is not contraindicated from the point of view of their effect on lysozyme activity.", "contents": "[Lysozyme activity in the leukocytes and blood serum of white rats administered massive doses of penicillin preparations]. Activity of lysozyme in the blood serum and leucocytes was determined. The experiments were carried out on albino unbred rats weighing 170 to 200 gm. Benzylpenicillin and oxacillin were administered intramuscularly in doses of 500000 Units/kg or 20000 gamma/kg once every 24 hours for 2, 4 and 6 days. The activity of lysozyme was determined by the turbidimetric and agar-diffusion methods. It was found that the activity of lysozyme in the leucocytes increased by the 5th day accompanied by a simultaneous decrease in its level in the serum followed by reaching the initial values. The data are indicative of the fact that the use of antibiotics in mega-doses is not contraindicated from the point of view of their effect on lysozyme activity."} {"id": "PMID:1275476", "title": "[Rifampicin in the therapy of gonorrheal urethritis in men].", "content": "The therapeutic efficiency of benemycin (rifampicin of Polish production), a semisynthetic antibiotic was studied in 96 male cases with gonorrhea urethritis. The antibiotic was used in a dose of 300 mg every 6 hours (2.1--3gm for the treatment course depending on the desease severity). Observation of the patients for 1--2 months showed etiological recovery in 91 (94.8 per cent) out of 96 patients. Postgonorrhea inflammatory processes were observed in 8.7 per cent of the cases. For studying late results of the treatmant 62 patients were observed for 3 to 12 months. Gonococci were isolated from none of the patients. No side reactions were found in the patients treated with rifampicin.", "contents": "[Rifampicin in the therapy of gonorrheal urethritis in men]. The therapeutic efficiency of benemycin (rifampicin of Polish production), a semisynthetic antibiotic was studied in 96 male cases with gonorrhea urethritis. The antibiotic was used in a dose of 300 mg every 6 hours (2.1--3gm for the treatment course depending on the desease severity). Observation of the patients for 1--2 months showed etiological recovery in 91 (94.8 per cent) out of 96 patients. Postgonorrhea inflammatory processes were observed in 8.7 per cent of the cases. For studying late results of the treatmant 62 patients were observed for 3 to 12 months. Gonococci were isolated from none of the patients. No side reactions were found in the patients treated with rifampicin."} {"id": "PMID:1275477", "title": "[Blood coagulation system in oncological patients treated with rubomycin, adriamycin and carminomycin].", "content": "Systems of blood coagulation in patients treated with antibiotics of the anthracycline group were studied. Rubomycin was used in the treatment of patients with acute leukemia Adriamycin and carminomycin were used in the treatment of patients with solid tumors. The antibiotics affected the process of blood coagulation mainly through their cytostatic effect on thrombocytopoesis. Thrombocytopenia induced deficit of thrombocytal factors participating in the process of blood coagulation which resulted in hypocoagulation and hemorrhagic complications. The plasmic factors did not significantly change during the antibiotic therapy. A tendency to decrease in the levels of prothrombine, fibrinase and fibrinogen was noted which was possible due to an inhibitory effect of the antibiotics on the function of the reticuloendothelial tissue cells or indirectly to suppression of the tumor process. More pronounced changes in the system of blood coagulation of patients treated with rubomycin were probably associated with inferiority of the thrombocytal apparatus of the patients with acute leukemia treated with the antibiotic.", "contents": "[Blood coagulation system in oncological patients treated with rubomycin, adriamycin and carminomycin]. Systems of blood coagulation in patients treated with antibiotics of the anthracycline group were studied. Rubomycin was used in the treatment of patients with acute leukemia Adriamycin and carminomycin were used in the treatment of patients with solid tumors. The antibiotics affected the process of blood coagulation mainly through their cytostatic effect on thrombocytopoesis. Thrombocytopenia induced deficit of thrombocytal factors participating in the process of blood coagulation which resulted in hypocoagulation and hemorrhagic complications. The plasmic factors did not significantly change during the antibiotic therapy. A tendency to decrease in the levels of prothrombine, fibrinase and fibrinogen was noted which was possible due to an inhibitory effect of the antibiotics on the function of the reticuloendothelial tissue cells or indirectly to suppression of the tumor process. More pronounced changes in the system of blood coagulation of patients treated with rubomycin were probably associated with inferiority of the thrombocytal apparatus of the patients with acute leukemia treated with the antibiotic."} {"id": "PMID:1275478", "title": "[Madumycin biosynthesis by an Actinomadure flava culture under conditions of varying aeration].", "content": "Production of madumycin I and madumycin II by 2 strains of Actinomadure flava 2171 was studied. Intensive aeration was an obligatory condition for the antibiotic biosynthesis. The content of madumycins I and II in the culture fluid depended on the strain, aeration conditions and fermentation cycle. Strain 2171/852 produced maximum amounts of madumycin I and madumycin II by the 2nd--3rd and 5th days of cultivation respectively. Strain 2171/2544 mainly produced madumycin I during the whole period of fermentation.", "contents": "[Madumycin biosynthesis by an Actinomadure flava culture under conditions of varying aeration]. Production of madumycin I and madumycin II by 2 strains of Actinomadure flava 2171 was studied. Intensive aeration was an obligatory condition for the antibiotic biosynthesis. The content of madumycins I and II in the culture fluid depended on the strain, aeration conditions and fermentation cycle. Strain 2171/852 produced maximum amounts of madumycin I and madumycin II by the 2nd--3rd and 5th days of cultivation respectively. Strain 2171/2544 mainly produced madumycin I during the whole period of fermentation."} {"id": "PMID:1275479", "title": "[Structure of the carbohydrate moiety of actinoidins A and B].", "content": "The structure of the carbohydrate moiety of actinoidins A and B was found with partial acid hydrolysis (metanolysis) of the antibiotics and their methyl derivatives and the method of periodate oxidation. Actinoidins A and B had 3 carbohydrate branches presented by the residues of monosugars of D-mannopyranose and 2, 3, 6-tridesoxy-3-amino-4-O-methyl-L-arabinopyranose(L-actinosamine) and disaccharide of 2-O-(2, 3, 6-tridesoxy-3-amino-L-arabinopyranosyl)-D-glucopyranose.", "contents": "[Structure of the carbohydrate moiety of actinoidins A and B]. The structure of the carbohydrate moiety of actinoidins A and B was found with partial acid hydrolysis (metanolysis) of the antibiotics and their methyl derivatives and the method of periodate oxidation. Actinoidins A and B had 3 carbohydrate branches presented by the residues of monosugars of D-mannopyranose and 2, 3, 6-tridesoxy-3-amino-4-O-methyl-L-arabinopyranose(L-actinosamine) and disaccharide of 2-O-(2, 3, 6-tridesoxy-3-amino-L-arabinopyranosyl)-D-glucopyranose."} {"id": "PMID:1275481", "title": "[Effect of amphoterecin B on the plasma membranes of a tissue culture of puppy kidney].", "content": "The effect of amphotoericin B on the chemical composition of the plasmic membranes of the puppy kidney tissue was studied. It was shown that amphotericin B in a concentration of 10 Units/ml induced changes in the quantitative content of proteins, lipids and RNA in the chemical composition of the plasmic membranes. The effect of amphotericin B on the composition of proteins and lipids in the membranes was also studied. It was found with the method of electrophoresis in polyacrylamide gel that after exposure of the culture cells to the antibiotic significant shifts in the composition of the membrane proteins took place. According to the findings of thin-layer chromatography amphotericin B markedly changed the quantitative content of the fractions in the composition of lipids in the plasmic membranes. Significant deviations under the effect of the antibiotic were observed in the quantitative ratio of separate fatty acids contained in the lipids of the membrane preparations studied. On the basis of the results obtained it was supposed that the mode of action of amphotericin B on the cell was associated with impairement of the plasmic membrane structure by the antibiotic.", "contents": "[Effect of amphoterecin B on the plasma membranes of a tissue culture of puppy kidney]. The effect of amphotoericin B on the chemical composition of the plasmic membranes of the puppy kidney tissue was studied. It was shown that amphotericin B in a concentration of 10 Units/ml induced changes in the quantitative content of proteins, lipids and RNA in the chemical composition of the plasmic membranes. The effect of amphotericin B on the composition of proteins and lipids in the membranes was also studied. It was found with the method of electrophoresis in polyacrylamide gel that after exposure of the culture cells to the antibiotic significant shifts in the composition of the membrane proteins took place. According to the findings of thin-layer chromatography amphotericin B markedly changed the quantitative content of the fractions in the composition of lipids in the plasmic membranes. Significant deviations under the effect of the antibiotic were observed in the quantitative ratio of separate fatty acids contained in the lipids of the membrane preparations studied. On the basis of the results obtained it was supposed that the mode of action of amphotericin B on the cell was associated with impairement of the plasmic membrane structure by the antibiotic."} {"id": "PMID:1275482", "title": "[Penicillin distribution in the body of animals with experimental chronic pneumonia when administered repeatedly in combination with prednisolone].", "content": "The dynamics of penicillin concentrations in the blood and lung tissue of animals with chronic experimental pneumonia after its repeated administration in combination with prednisolone was studied. An increase in the period, during which the antibiotic was found in the lung tissue of the animals under conditions of its repeated use with prednisolone was shown.", "contents": "[Penicillin distribution in the body of animals with experimental chronic pneumonia when administered repeatedly in combination with prednisolone]. The dynamics of penicillin concentrations in the blood and lung tissue of animals with chronic experimental pneumonia after its repeated administration in combination with prednisolone was studied. An increase in the period, during which the antibiotic was found in the lung tissue of the animals under conditions of its repeated use with prednisolone was shown."} {"id": "PMID:1275483", "title": "[Comparative study of the semisynthetic penicillins in the experimental therapy of pneumococcal and streptococcal infections in mice].", "content": "Penicillins were studied comparatively on mice with infections caused by pneumococci and streptococci. It was shown that klomethacillin was superior by its chemotherapeutic effect to other penicillins in treatment of pneumococcal septicemia when used subcutaneously or intragastrically. Ampicillin was superior in treatment of streptococcal infection.", "contents": "[Comparative study of the semisynthetic penicillins in the experimental therapy of pneumococcal and streptococcal infections in mice]. Penicillins were studied comparatively on mice with infections caused by pneumococci and streptococci. It was shown that klomethacillin was superior by its chemotherapeutic effect to other penicillins in treatment of pneumococcal septicemia when used subcutaneously or intragastrically. Ampicillin was superior in treatment of streptococcal infection."} {"id": "PMID:1275484", "title": "[Effect of chymotrypsin on the urinary excretion of antibiotics in rabbits].", "content": "The effect of cymotrypsin on excretion of penicillin, methicillin, oxacillin, streptomycin and gentamycin with urine including the kidney clearance was studied on rabbits. It was found that the enzyme introduced intramuscularly in a dose of 20 mg/kg increased excretion of penicillin, methicillin, oxacillin and gentamycin by 37, 24, 26 and 16 per cent respectively. The only exclusion was streptomycin. Chymotrypsin increased the kidney clearance of penicillin, methicillin, oxacillin, streptomycin and gentamycin by 1.7, 1.9, 2.2, 1.2 and 1.5 times respectively.", "contents": "[Effect of chymotrypsin on the urinary excretion of antibiotics in rabbits]. The effect of cymotrypsin on excretion of penicillin, methicillin, oxacillin, streptomycin and gentamycin with urine including the kidney clearance was studied on rabbits. It was found that the enzyme introduced intramuscularly in a dose of 20 mg/kg increased excretion of penicillin, methicillin, oxacillin and gentamycin by 37, 24, 26 and 16 per cent respectively. The only exclusion was streptomycin. Chymotrypsin increased the kidney clearance of penicillin, methicillin, oxacillin, streptomycin and gentamycin by 1.7, 1.9, 2.2, 1.2 and 1.5 times respectively."} {"id": "PMID:1275485", "title": "[Acidocillin concentration in middle ear exudate].", "content": "Acidocillin levels were determined in the middle ear exudates and serum of patients with acute exudative otitis media after oral administration of the drug. Acidocillin rapidly diffused exudate into the ear and its level in the exudate in 1 hour was 0-1.7 gamma/ml. At the same time the serum levels ranges within 4 to 25 gamma/ml. acidocillin remained longer in the ear exudate than in the serum. In 12 hours 0.2 to 1.3 gamma/ml of acidocillin was still found in the exudates, while there was no antibiotic in the serum.", "contents": "[Acidocillin concentration in middle ear exudate]. Acidocillin levels were determined in the middle ear exudates and serum of patients with acute exudative otitis media after oral administration of the drug. Acidocillin rapidly diffused exudate into the ear and its level in the exudate in 1 hour was 0-1.7 gamma/ml. At the same time the serum levels ranges within 4 to 25 gamma/ml. acidocillin remained longer in the ear exudate than in the serum. In 12 hours 0.2 to 1.3 gamma/ml of acidocillin was still found in the exudates, while there was no antibiotic in the serum."} {"id": "PMID:1275486", "title": "[Macrolide antibiotics for oral intake in the treatment and prevention of suppurative surgical infection].", "content": "The authors studied the clinical efficacy of antibiotics of the macrolides group--erythromycin, oleandomycin, triacetylalleandomycin and leukomycin--in complex treatment of 280 patients with suppurative surgical infection caused by a gram-positive, mainly staphylococcal, microbial flora. Various medicinal forms were used: tablets, capsules, granules, syrup. Efficacy of treatment comprised 70-78 per cent. Tolerance of antibiotics was good in the majority of patients.", "contents": "[Macrolide antibiotics for oral intake in the treatment and prevention of suppurative surgical infection]. The authors studied the clinical efficacy of antibiotics of the macrolides group--erythromycin, oleandomycin, triacetylalleandomycin and leukomycin--in complex treatment of 280 patients with suppurative surgical infection caused by a gram-positive, mainly staphylococcal, microbial flora. Various medicinal forms were used: tablets, capsules, granules, syrup. Efficacy of treatment comprised 70-78 per cent. Tolerance of antibiotics was good in the majority of patients."} {"id": "PMID:1275487", "title": "Microbial degradation of oil spills enhanced by a slow-release fertilizer.", "content": "The improved cleanup of marine oil spills by stimulating biodegradation through the use of a slow-release fertilizer is reported. A paraffin-supported fertilizer containing MgNH4PO4 as active ingredient was developed and evaluated in laboratory and field experiments using quantitative infrared spectrometry and chromatographic techniques. The biodegradation of Sarir crude oil in the sea was considerably enhanced by paraffin-supported fertilizer. After 21 days 63% had disappeared as compared to 40% in the control area.", "contents": "Microbial degradation of oil spills enhanced by a slow-release fertilizer. The improved cleanup of marine oil spills by stimulating biodegradation through the use of a slow-release fertilizer is reported. A paraffin-supported fertilizer containing MgNH4PO4 as active ingredient was developed and evaluated in laboratory and field experiments using quantitative infrared spectrometry and chromatographic techniques. The biodegradation of Sarir crude oil in the sea was considerably enhanced by paraffin-supported fertilizer. After 21 days 63% had disappeared as compared to 40% in the control area."} {"id": "PMID:1275488", "title": "Teratogenicity of patulin and patulin adducts formed with cysteine.", "content": "The mean lethal dose of patulin for the chicken embryo injected in the air cell before incubation was determined to be 68.7 mug and that for the 4-day-old embryo was 2.35 mug. Both patulin (1 to 2 mug/egg) and the reaction mixture between patulin and cysteine (15 to 150 mug of patulin equivalents) were teratogenic to the chicken embryo. At least two ninhydrin-negative and four ninhydrin-positive products were formed during the latter reaction. Our explanation of the reaction mechanism remains to be elaborated.", "contents": "Teratogenicity of patulin and patulin adducts formed with cysteine. The mean lethal dose of patulin for the chicken embryo injected in the air cell before incubation was determined to be 68.7 mug and that for the 4-day-old embryo was 2.35 mug. Both patulin (1 to 2 mug/egg) and the reaction mixture between patulin and cysteine (15 to 150 mug of patulin equivalents) were teratogenic to the chicken embryo. At least two ninhydrin-negative and four ninhydrin-positive products were formed during the latter reaction. Our explanation of the reaction mechanism remains to be elaborated."} {"id": "PMID:1275489", "title": "Use of a quantitative oxidase test for characterizing oxidative metabolism in bacteria.", "content": "It was possible to quantitate the terminal oxidase(s) reaction using bacterial resting-cell suspensions and demonstrate the usefulness of this reaction for taxonomic purposes. Resting-cell suspensions of physiologically diverse bacteria were examined for their capabilities of oxidizing N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) using a manometric assay. For organisms having this capability, it was possible to calculate the conventional TMPD oxidase Q(O2) value (microliters of O2 consumed per hour per milligram [dry weight]). All cultures were grown heterotrophically at 30 C, under identical nutritional conditions, and were harvested at the late-logarithmic growth phase. The TMPD oxidase Q(O2) values showed perfect correlation with the Kovacs oxidase test and, in addition, it was possible to define quantitatively that point which separated oxidase-positive from oxidase-negative bacteria. Oxidase-negative bacteria exhibited a TMPD oxidase Q(O2) value (after correcting for the endogenous by substraction) of less than or equal 33 and had an uncorrected TMPD/endogenous ratio of less than or equal 5. The TMPD oxidase Q(O2) values were also correlated with the data obtained for the Hugh-Leifson Oxferm test. In general, bacteria that exhibited a respiratory mechanism had high TMPD oxidase values, whereas fermentative organsims had low TMPD oxidase activity. All exceptions to this are noted. This quantitative study also demonstrated that organisms that (i) lack a type c cytochrome, or (ii) lack a cytochrome-containing electron transport system, like the lactic acid bacteria, exhibited low or negligible TMPD oxidase Q(O2) values. From the 79 bacterial species (36 genera) examined, it appears that this quantitative oxidase test has taxonomic value that can differentiate the oxidative relationships between bacteria at the subspecies, species, and genera levels.", "contents": "Use of a quantitative oxidase test for characterizing oxidative metabolism in bacteria. It was possible to quantitate the terminal oxidase(s) reaction using bacterial resting-cell suspensions and demonstrate the usefulness of this reaction for taxonomic purposes. Resting-cell suspensions of physiologically diverse bacteria were examined for their capabilities of oxidizing N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) using a manometric assay. For organisms having this capability, it was possible to calculate the conventional TMPD oxidase Q(O2) value (microliters of O2 consumed per hour per milligram [dry weight]). All cultures were grown heterotrophically at 30 C, under identical nutritional conditions, and were harvested at the late-logarithmic growth phase. The TMPD oxidase Q(O2) values showed perfect correlation with the Kovacs oxidase test and, in addition, it was possible to define quantitatively that point which separated oxidase-positive from oxidase-negative bacteria. Oxidase-negative bacteria exhibited a TMPD oxidase Q(O2) value (after correcting for the endogenous by substraction) of less than or equal 33 and had an uncorrected TMPD/endogenous ratio of less than or equal 5. The TMPD oxidase Q(O2) values were also correlated with the data obtained for the Hugh-Leifson Oxferm test. In general, bacteria that exhibited a respiratory mechanism had high TMPD oxidase values, whereas fermentative organsims had low TMPD oxidase activity. All exceptions to this are noted. This quantitative study also demonstrated that organisms that (i) lack a type c cytochrome, or (ii) lack a cytochrome-containing electron transport system, like the lactic acid bacteria, exhibited low or negligible TMPD oxidase Q(O2) values. From the 79 bacterial species (36 genera) examined, it appears that this quantitative oxidase test has taxonomic value that can differentiate the oxidative relationships between bacteria at the subspecies, species, and genera levels."} {"id": "PMID:1275490", "title": "Effect of dietary aflatoxin on fertility, hatchability, and progeny performance of broiler breeder hens.", "content": "The effects of aflatoxin on egg production, fertility, hatchability, and progeny performance were investigated by feeding dietary aflatoxin at dose levels of 0,5, and 10 mug/g to mature broiler breeder hens for 4 weeks. Sixteen hens were used for each dietary dose level. Egg production decreased significantly during weeks 3 and 4 after initiation of toxin feeding for hens fed 10 and 5 mum of aflatoxin per g of diet respectively. Whereas fertility was not affected by dietary aflatoxin, hatchability of fertile eggs decreased significantly within week 1 of toxin feeding. Hatchability of fertile eggs collected during week 1 of the treatment period was 95.1, 68.9, and 48.5% for the control, 5- and 10-mug/g groups, respectively. At the dose levels used in this study, no latent effects of the aflatoxin or its metabolites were observed on the performance of surviving chicks. Six hens from each experimental groups were necropsied at the end of the 4-week treatment period. These birds exhibited typical symptoms of aflatoxicosis, including enlarged, fatty and friable livers, and enlarged spleens.", "contents": "Effect of dietary aflatoxin on fertility, hatchability, and progeny performance of broiler breeder hens. The effects of aflatoxin on egg production, fertility, hatchability, and progeny performance were investigated by feeding dietary aflatoxin at dose levels of 0,5, and 10 mug/g to mature broiler breeder hens for 4 weeks. Sixteen hens were used for each dietary dose level. Egg production decreased significantly during weeks 3 and 4 after initiation of toxin feeding for hens fed 10 and 5 mum of aflatoxin per g of diet respectively. Whereas fertility was not affected by dietary aflatoxin, hatchability of fertile eggs decreased significantly within week 1 of toxin feeding. Hatchability of fertile eggs collected during week 1 of the treatment period was 95.1, 68.9, and 48.5% for the control, 5- and 10-mug/g groups, respectively. At the dose levels used in this study, no latent effects of the aflatoxin or its metabolites were observed on the performance of surviving chicks. Six hens from each experimental groups were necropsied at the end of the 4-week treatment period. These birds exhibited typical symptoms of aflatoxicosis, including enlarged, fatty and friable livers, and enlarged spleens."} {"id": "PMID:1275491", "title": "Estimation of viable airborne microbes downwind from a point source.", "content": "Modification of the Pasquill atmospheric diffusion equations for estimating viable microbial airborne cell concentrations downwind form a continuous point source is presented. A graphical method is given to estimate the ground level cell concentration given (i) microbial death rate, (ii) mean wind speed, (iii) atmospheric stability class, (iv) downwind sample distance from the source, and (v) source height.", "contents": "Estimation of viable airborne microbes downwind from a point source. Modification of the Pasquill atmospheric diffusion equations for estimating viable microbial airborne cell concentrations downwind form a continuous point source is presented. A graphical method is given to estimate the ground level cell concentration given (i) microbial death rate, (ii) mean wind speed, (iii) atmospheric stability class, (iv) downwind sample distance from the source, and (v) source height."} {"id": "PMID:1275492", "title": "Airborne coliphages from wastewater treatment facilities.", "content": "The emission (from wastewater treatment plants) of airborne coliphages that form plaques on two strains of Escherichia coli was investigated. Two activated-sludge and two trickling-filter plants were studied. Field sampling procedures used large-volume air samplers with recirculation devices. Coliphages were enumerated by a most-probable-number (MPN) procedure. Temperature, relative humidity, windspeed, and presence of sunlight were monitored. Concurrent samples of sewage were taken during each air-sampling run. Average coliphage levels in the airborne emissions of trickling-filter beds and activated-sludge units were 2.84 X 10(-1) and 3.02 X 10(-1) MPN/m3, respectively, for all positive observations, and sewage liquor concentrations from the sources were 4.48 X 10(5) and 2.94 X 10(6) plaque-forming units/liter, respectively, depending upon the E. coli host used for assay. This work establishes minimal airborne-coliphage concentrations from the plants studied. The procedures employed will be useful in evaluating the animal virus levels in these emissions.", "contents": "Airborne coliphages from wastewater treatment facilities. The emission (from wastewater treatment plants) of airborne coliphages that form plaques on two strains of Escherichia coli was investigated. Two activated-sludge and two trickling-filter plants were studied. Field sampling procedures used large-volume air samplers with recirculation devices. Coliphages were enumerated by a most-probable-number (MPN) procedure. Temperature, relative humidity, windspeed, and presence of sunlight were monitored. Concurrent samples of sewage were taken during each air-sampling run. Average coliphage levels in the airborne emissions of trickling-filter beds and activated-sludge units were 2.84 X 10(-1) and 3.02 X 10(-1) MPN/m3, respectively, for all positive observations, and sewage liquor concentrations from the sources were 4.48 X 10(5) and 2.94 X 10(6) plaque-forming units/liter, respectively, depending upon the E. coli host used for assay. This work establishes minimal airborne-coliphage concentrations from the plants studied. The procedures employed will be useful in evaluating the animal virus levels in these emissions."} {"id": "PMID:1275493", "title": "Resistance of a strain of Pseudomonas cepacia to esters of p-hydroxybenzoic acid.", "content": "Cells of a strain of Pseudomonas cepacia were isolated from an oil-in-water emulsion containing methyl and propyl p-hydroxybenzoates (methylparaben and propylparaben) as preservative additives. This strain demonstrated the ability to destroy these additives, to utilize the propyl ester as sole carbon source, and to hydrolyze the methyl ester. When the isolate was grown on Eugon agar, exposure to the methyl ester killed 99.9% of the inoculum, but the surviving cells grew logarithmically. On the other hand, cells grown on media containing propylparaben were less susceptible when subsequently exposed to emulsions containing methylparaben. These observations demonstrate one mechanism by which microorganisms develop resistance to antimicrobial preservatives.", "contents": "Resistance of a strain of Pseudomonas cepacia to esters of p-hydroxybenzoic acid. Cells of a strain of Pseudomonas cepacia were isolated from an oil-in-water emulsion containing methyl and propyl p-hydroxybenzoates (methylparaben and propylparaben) as preservative additives. This strain demonstrated the ability to destroy these additives, to utilize the propyl ester as sole carbon source, and to hydrolyze the methyl ester. When the isolate was grown on Eugon agar, exposure to the methyl ester killed 99.9% of the inoculum, but the surviving cells grew logarithmically. On the other hand, cells grown on media containing propylparaben were less susceptible when subsequently exposed to emulsions containing methylparaben. These observations demonstrate one mechanism by which microorganisms develop resistance to antimicrobial preservatives."} {"id": "PMID:1275494", "title": "Activated sludge degradation of adipic acid esters.", "content": "The biodegradability of three aliphatic adipic acid diesters and a 1,3-butylene glycol adipic acid polyester was determined in acclimated, activated sludge systems. Rapid primary biodegradation from 67 to 99+% was observed at 3- and 13-mg/liter feed levels for di-n-hexyl adipate, di(2-ethylhexyl) adipate, and di(heptyl, nonyl) adipate in 24 h. When acclimated, activated sludge microorganisms were employed as the seed for two carbon dioxide evolution procedures, greater than 75% of the theoretical carbon dioxide was evolved for the three diesters and the polyester in a 35-day test period. The essentially complete biodegradation observed in these studies suggests that these esters would not persist when exposed to similar mixed microbial populations in the environment.", "contents": "Activated sludge degradation of adipic acid esters. The biodegradability of three aliphatic adipic acid diesters and a 1,3-butylene glycol adipic acid polyester was determined in acclimated, activated sludge systems. Rapid primary biodegradation from 67 to 99+% was observed at 3- and 13-mg/liter feed levels for di-n-hexyl adipate, di(2-ethylhexyl) adipate, and di(heptyl, nonyl) adipate in 24 h. When acclimated, activated sludge microorganisms were employed as the seed for two carbon dioxide evolution procedures, greater than 75% of the theoretical carbon dioxide was evolved for the three diesters and the polyester in a 35-day test period. The essentially complete biodegradation observed in these studies suggests that these esters would not persist when exposed to similar mixed microbial populations in the environment."} {"id": "PMID:1275495", "title": "Environmental factors influencing the rate of hydrocarbon oxidation in temperate lakes.", "content": "Rates of hydrocarbon biodegradation were estimated by following oxygen uptake during mineral oil oxidation or oxidation of [1-14C]hexadecane to 14CO2, when these substrates were added to natural water samples from Wisconsin lakes. A lag phase preceded hydrocarbon oxidation, the length of which depended on population density or on factors influencing growth rate and on the presence of nonhydrocarbon organic compounds. Hydrocarbon oxidation was coincident with growth and presumably represented the development of indigenous hydrocarbon-degrading microorganisms in response to hydrocarbon additions. In detailed studies in Lake Mendota, it was found that, despite the continued presence of hydrocarbon-degrading microorganisms in water samples, seasonal variations in the rates of mineral oil and hexadecane oxidation occurred which correlated with seasonal changes in temperature and dissolved inorganic nitrogen and phosphorus. The temperature optimum for oil biodegradation remained at 20 to 25 C throughout the year, so that temperature was the main limiting factor during winter, spring, and fall. During summer, when temperatures were optimal, nutrient deficiencies limited oil biodegradation, and higher rates could be obtained by addition of nitrogen and phosphorus. The rates of hydrocarbon biodegradation were thus high only for about 1 month of the ice-free period, when temperature and nutrient supply were optimal. Nutrient limitation of oil biodegradation was also demonstrated in 25 nutrient-poor lakes of northern Wisconsin, although in almost every case oil-degrading bacteria were detected. Knowledge of temperature and nutrient limitations thus will help in predicting the fate of hydrocarbon pollutants in freshwater.", "contents": "Environmental factors influencing the rate of hydrocarbon oxidation in temperate lakes. Rates of hydrocarbon biodegradation were estimated by following oxygen uptake during mineral oil oxidation or oxidation of [1-14C]hexadecane to 14CO2, when these substrates were added to natural water samples from Wisconsin lakes. A lag phase preceded hydrocarbon oxidation, the length of which depended on population density or on factors influencing growth rate and on the presence of nonhydrocarbon organic compounds. Hydrocarbon oxidation was coincident with growth and presumably represented the development of indigenous hydrocarbon-degrading microorganisms in response to hydrocarbon additions. In detailed studies in Lake Mendota, it was found that, despite the continued presence of hydrocarbon-degrading microorganisms in water samples, seasonal variations in the rates of mineral oil and hexadecane oxidation occurred which correlated with seasonal changes in temperature and dissolved inorganic nitrogen and phosphorus. The temperature optimum for oil biodegradation remained at 20 to 25 C throughout the year, so that temperature was the main limiting factor during winter, spring, and fall. During summer, when temperatures were optimal, nutrient deficiencies limited oil biodegradation, and higher rates could be obtained by addition of nitrogen and phosphorus. The rates of hydrocarbon biodegradation were thus high only for about 1 month of the ice-free period, when temperature and nutrient supply were optimal. Nutrient limitation of oil biodegradation was also demonstrated in 25 nutrient-poor lakes of northern Wisconsin, although in almost every case oil-degrading bacteria were detected. Knowledge of temperature and nutrient limitations thus will help in predicting the fate of hydrocarbon pollutants in freshwater."} {"id": "PMID:1275496", "title": "Effect of a sputum digestant on the viabiltiy of Mycobacterium fortuitum.", "content": "A microcolony technique has been demonstrated as being useful for the rapid determination of the viabilities of single cells of Myocbacterium fortuitum. Cultures of M. fortuitum grown to early logarithmic phase in broth were treated with the sputum digestant N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) for periods of 10 to 40 s. After growth for three generations (7.5 h) on agar films, viabilities were determined by counting under a phase contrast microscope. The viable mycobacteria grew into microcolonies that exhibited extensive branching, whereas the nonviable mycobacteria remained as single cells. Sputum was mixed with some broth cultures before treatment to stimulate the digestion process in a clinical laboratory. When broth cultures were treated with sputum digestant for 40 s, only 2.8% of the cells remained viable. When the broth cultures were mixed in a ratio of 1:4 with sputum and then treated for 40 s, 16.4% of the cells remained viable. The results also indicate M. fortuitum is very sensitive to the digestant. The results also indicate that a microcolony technique could be used for the assessment of the viability of mycobacteria.", "contents": "Effect of a sputum digestant on the viabiltiy of Mycobacterium fortuitum. A microcolony technique has been demonstrated as being useful for the rapid determination of the viabilities of single cells of Myocbacterium fortuitum. Cultures of M. fortuitum grown to early logarithmic phase in broth were treated with the sputum digestant N-acetyl-L-cysteine-sodium hydroxide (NALC-NaOH) for periods of 10 to 40 s. After growth for three generations (7.5 h) on agar films, viabilities were determined by counting under a phase contrast microscope. The viable mycobacteria grew into microcolonies that exhibited extensive branching, whereas the nonviable mycobacteria remained as single cells. Sputum was mixed with some broth cultures before treatment to stimulate the digestion process in a clinical laboratory. When broth cultures were treated with sputum digestant for 40 s, only 2.8% of the cells remained viable. When the broth cultures were mixed in a ratio of 1:4 with sputum and then treated for 40 s, 16.4% of the cells remained viable. The results also indicate M. fortuitum is very sensitive to the digestant. The results also indicate that a microcolony technique could be used for the assessment of the viability of mycobacteria."} {"id": "PMID:1275520", "title": "Acrodermatitis enteropathico. Abnormalities of fat metabolism and integumental ultrastructures in infants.", "content": "Acrodermatitis enteropathica is a rare disease of childhood, characterized by periorificial and perioral dermatitis, acrodermatitis, diarrhea, and alopecia. Two patients were successfully treated with diiodohydroxyquin (Diodoquin). Lipid concentrations disclosed abnormal distribution of fats that resembled those of less mature infants fed diets low in linoleic acid even though the patients were actually on diets with high linoleic acid levels. Fatty acid distribution showed increased levels of linoleic acid that correlated with clinical improvement in the patient who was more ill. Skin fatty acids showed decreased levels of linoleic acid. Electron micrographs and histochemical staining disclosed increased lipids droplets in epidermal cells. Linoleic acid and zinc may have a role in the origin of the disease, and measurement of both skin and serum linoleic acid is suggested in the evaluation of its progress.", "contents": "Acrodermatitis enteropathico. Abnormalities of fat metabolism and integumental ultrastructures in infants. Acrodermatitis enteropathica is a rare disease of childhood, characterized by periorificial and perioral dermatitis, acrodermatitis, diarrhea, and alopecia. Two patients were successfully treated with diiodohydroxyquin (Diodoquin). Lipid concentrations disclosed abnormal distribution of fats that resembled those of less mature infants fed diets low in linoleic acid even though the patients were actually on diets with high linoleic acid levels. Fatty acid distribution showed increased levels of linoleic acid that correlated with clinical improvement in the patient who was more ill. Skin fatty acids showed decreased levels of linoleic acid. Electron micrographs and histochemical staining disclosed increased lipids droplets in epidermal cells. Linoleic acid and zinc may have a role in the origin of the disease, and measurement of both skin and serum linoleic acid is suggested in the evaluation of its progress."} {"id": "PMID:1275521", "title": "Green autofluorescence in human epidermal cells.", "content": "A characteristic and natural autofluorescence that appears brilliant green in frozen sections of untreated skin when viewed under the fluorescent microscope is demonstrated. Study with various barrier filters and exciter filters indicates that the optimum absorption for visualization of this is 300 to 330 nm, and the optimum fluorescence is between 500 and 530 nm under the conditions used. Clinical study of skin from 52 patients including black, white, Puerto Rican, and Chinese indicates a relationship between skin color and intensity of autofluorescence. In addition, the cellular localization of autofluorescence corresponds to sites of melanin. Cells in the basal layer are involved most conspicuously and nuclei are spared.", "contents": "Green autofluorescence in human epidermal cells. A characteristic and natural autofluorescence that appears brilliant green in frozen sections of untreated skin when viewed under the fluorescent microscope is demonstrated. Study with various barrier filters and exciter filters indicates that the optimum absorption for visualization of this is 300 to 330 nm, and the optimum fluorescence is between 500 and 530 nm under the conditions used. Clinical study of skin from 52 patients including black, white, Puerto Rican, and Chinese indicates a relationship between skin color and intensity of autofluorescence. In addition, the cellular localization of autofluorescence corresponds to sites of melanin. Cells in the basal layer are involved most conspicuously and nuclei are spared."} {"id": "PMID:1275522", "title": "Lupus erythematosus-like syndrome with a familial deficiency of C2.", "content": "Several cases of isolated C2 deficiency in man have been reported in the medical literature. The earliest cases did not seem to be associated with known diseases or syndromes; more recently, reports of C2 deficiency associated with systemic lupus erythematosus; anaphylactoid purpura, recurrent infections, and dermatomyositis have appeared. We report here another case of C2 deficiency. The propositus, a 24-year-old woman, had a lupus erythematosus-like rash and a history of arthralgia, as well as a selective deficiency of C2. Studies of hemolytic C2 of the immediate members of her family indicate an autosomal-recessive mode of inheritance. These findings add to the increasing evidence that a C2 deficiency predisposes some persons to serious vascular diseases.", "contents": "Lupus erythematosus-like syndrome with a familial deficiency of C2. Several cases of isolated C2 deficiency in man have been reported in the medical literature. The earliest cases did not seem to be associated with known diseases or syndromes; more recently, reports of C2 deficiency associated with systemic lupus erythematosus; anaphylactoid purpura, recurrent infections, and dermatomyositis have appeared. We report here another case of C2 deficiency. The propositus, a 24-year-old woman, had a lupus erythematosus-like rash and a history of arthralgia, as well as a selective deficiency of C2. Studies of hemolytic C2 of the immediate members of her family indicate an autosomal-recessive mode of inheritance. These findings add to the increasing evidence that a C2 deficiency predisposes some persons to serious vascular diseases."} {"id": "PMID:1275523", "title": "Dependence of corticosteroid penetration on the vehicle.", "content": "The penetration of corticosteroids through epidermal membranes in vitro proved to be better when the corticosteroid was dissolved in, or salicylic acid was added to, the vehicle. Hydrocortisone 17 butyrate (HCB) penetration from an ethanolic solution or a vehicle containing propylene glycol (PG) exceeds the penetration from an oil-in-water (O/W) cream or a petrolatum-polyethylene base (Plastibase), both without PG. The addition of PG led to higher penetration from a cream containing 0.2% HCB as compared with that from one containing 0.1% HCB. When the atmosphere on the donor side of the chamber was kept dry with a molecular sieve, the penetration from an O/W cream containing PG was enhanced, whereas that from an O/W cream without PG was substantially diminished.", "contents": "Dependence of corticosteroid penetration on the vehicle. The penetration of corticosteroids through epidermal membranes in vitro proved to be better when the corticosteroid was dissolved in, or salicylic acid was added to, the vehicle. Hydrocortisone 17 butyrate (HCB) penetration from an ethanolic solution or a vehicle containing propylene glycol (PG) exceeds the penetration from an oil-in-water (O/W) cream or a petrolatum-polyethylene base (Plastibase), both without PG. The addition of PG led to higher penetration from a cream containing 0.2% HCB as compared with that from one containing 0.1% HCB. When the atmosphere on the donor side of the chamber was kept dry with a molecular sieve, the penetration from an O/W cream containing PG was enhanced, whereas that from an O/W cream without PG was substantially diminished."} {"id": "PMID:1275524", "title": "Schistosomiasis. Paraplegia and ectopic skin lesions as admission symptoms.", "content": "A 33-year-old man, who had been a teacher in Africa from 1966 to 1969, was hospitalizaed in December 1973 for radiculomyelitis with progressive paraplegia and analgesia of the lower limbs. On his fourth day in the hospital, a pruritic, papular dermatitis appeared on both lower thoracic paraspinal areas. Microscopical examination of biopsy specimens of skin from those areas showed schistosome ova within many palisading granulomas in the dermis. The morphological features of the skin lesions, as seen by gross and microscopical examination, and the morphological and staining characteristics and the pathophysiology of the schostosome organism will be discussed. The longevity of the adult worm in the portal circulation is particularly important; a long interval may elapse between the time the patient leaves the area where he became infected and the time of appearance of the lesions.", "contents": "Schistosomiasis. Paraplegia and ectopic skin lesions as admission symptoms. A 33-year-old man, who had been a teacher in Africa from 1966 to 1969, was hospitalizaed in December 1973 for radiculomyelitis with progressive paraplegia and analgesia of the lower limbs. On his fourth day in the hospital, a pruritic, papular dermatitis appeared on both lower thoracic paraspinal areas. Microscopical examination of biopsy specimens of skin from those areas showed schistosome ova within many palisading granulomas in the dermis. The morphological features of the skin lesions, as seen by gross and microscopical examination, and the morphological and staining characteristics and the pathophysiology of the schostosome organism will be discussed. The longevity of the adult worm in the portal circulation is particularly important; a long interval may elapse between the time the patient leaves the area where he became infected and the time of appearance of the lesions."} {"id": "PMID:1275525", "title": "Lichen aureus.", "content": "A case of lichen aureus is described to record its clinical and histopathologic features. The disease is a variant of the pigmented purpuric eruptions, the common characteristic of which apparently resides in an abnormality of the minute cutaneous blood vessels.", "contents": "Lichen aureus. A case of lichen aureus is described to record its clinical and histopathologic features. The disease is a variant of the pigmented purpuric eruptions, the common characteristic of which apparently resides in an abnormality of the minute cutaneous blood vessels."} {"id": "PMID:1275526", "title": "Neonatal lupus erythematosus. Report of four cases with review of the literature.", "content": "We report four newborn infants with a distinctive evanescent cutaneous eruption that clinically and histologically resembled lupus erythematosus; two of the mothers had undifferentiated connective tissue disease. The tendency for lesions to occur in a periorbital location and the association of prominent telangiectasias were characteristic clinical signs in our patients. Immunoglobulin deposition at the basement membrane was demonstrated in one patient. Cytogenetic studies, done to exclude Bloom syndrome, revealed only nonspecific chromosomal abnormalities. A brief review of the literature, with speculations on the possible relationship of these changes to the occurrence of connective tissue disease in the mothers, is included in the discussion.", "contents": "Neonatal lupus erythematosus. Report of four cases with review of the literature. We report four newborn infants with a distinctive evanescent cutaneous eruption that clinically and histologically resembled lupus erythematosus; two of the mothers had undifferentiated connective tissue disease. The tendency for lesions to occur in a periorbital location and the association of prominent telangiectasias were characteristic clinical signs in our patients. Immunoglobulin deposition at the basement membrane was demonstrated in one patient. Cytogenetic studies, done to exclude Bloom syndrome, revealed only nonspecific chromosomal abnormalities. A brief review of the literature, with speculations on the possible relationship of these changes to the occurrence of connective tissue disease in the mothers, is included in the discussion."} {"id": "PMID:1275527", "title": "Mycobacterium kansasii infection with dermatologic manifestations.", "content": "A patient with cutaneous lesions as a manifestation of systemic infection with Mycobacterium kansasii is described. To our knowledge, this is the fourth reported case of a patient with dermatologic lesions secondary to M kansasii infection. A brief review of the classification and clinical presentations of atypical mycobacteria is given.", "contents": "Mycobacterium kansasii infection with dermatologic manifestations. A patient with cutaneous lesions as a manifestation of systemic infection with Mycobacterium kansasii is described. To our knowledge, this is the fourth reported case of a patient with dermatologic lesions secondary to M kansasii infection. A brief review of the classification and clinical presentations of atypical mycobacteria is given."} {"id": "PMID:1275528", "title": "Keratosis lichenoides chronica. Possible variant of lichen planus.", "content": "A chronic, asymptomatic, keratotic, papular eruption, present for 15 years and resistant to all modes of therapy, was observed in a 49-year-old woman. Many of the papules formed a reticulated configuration over the arms and legs. This case resembles several others that have been described in the literature under different names, ie, keratosis lichenoides chronica, porokeratosis striata, and lichen verrucosus et reticularis. It is likely that all of these names refer to the same condition, constituting a definite clinical entity, which, on the basis of histological study, may represent a variant of lichen planus.", "contents": "Keratosis lichenoides chronica. Possible variant of lichen planus. A chronic, asymptomatic, keratotic, papular eruption, present for 15 years and resistant to all modes of therapy, was observed in a 49-year-old woman. Many of the papules formed a reticulated configuration over the arms and legs. This case resembles several others that have been described in the literature under different names, ie, keratosis lichenoides chronica, porokeratosis striata, and lichen verrucosus et reticularis. It is likely that all of these names refer to the same condition, constituting a definite clinical entity, which, on the basis of histological study, may represent a variant of lichen planus."} {"id": "PMID:1275529", "title": "Hereditary phlebectasis of the lips. An autosomal dominant disorder.", "content": "A new hereditary syndrome is described in three, perhaps four generations, with a male-to-male transmission that denotes an autosomal dominant inheritance. Usually after the age of 40, there is a swelling of the lower lip by varicosities, a phenomenon usually seen in older individuals. Ten individuals have had this disorder. They do not seem to have any of the hereditary disorders that cause vascular changes in the lips, although the autosomal dominant disorder, Rendu-Osler-Weber syndrome most resembles this disease.", "contents": "Hereditary phlebectasis of the lips. An autosomal dominant disorder. A new hereditary syndrome is described in three, perhaps four generations, with a male-to-male transmission that denotes an autosomal dominant inheritance. Usually after the age of 40, there is a swelling of the lower lip by varicosities, a phenomenon usually seen in older individuals. Ten individuals have had this disorder. They do not seem to have any of the hereditary disorders that cause vascular changes in the lips, although the autosomal dominant disorder, Rendu-Osler-Weber syndrome most resembles this disease."} {"id": "PMID:1275530", "title": "Alopecia with fibrous dysplasia and osteomas of skin. A sign of polyostotic fibrous dysplasia.", "content": "Localized alopecia of the scalp proved to be the cutaneous sign of underlying polyostotic fibrous dysplasia (Albright disease). Histologically, the hair follicles had been replaced by a strange coil of fibrous tissue. Some of these follicular sites showed ossification so prominent as to be evident in soft tissue reoentgenograms. In this patient, the skin itself showed a fibrous dysplasia analogous to that which has always been identified as occurring within the bones in Albright disease. In her skin, it is the hair follicle that is the site of this dysplasia. The appearance of ossification in the skin and fibrous dysplasia in the bone would seem to demonstrate a delicate equilibrial balance between fibrous and osteal tissue in organs of a common mesenchymal origin. Localized connective tissue stromal dysplasia is believed to play a role in the pathogenesis of not only the bony, but aslo the pigmentary and endocrine abnormalities of the disease.", "contents": "Alopecia with fibrous dysplasia and osteomas of skin. A sign of polyostotic fibrous dysplasia. Localized alopecia of the scalp proved to be the cutaneous sign of underlying polyostotic fibrous dysplasia (Albright disease). Histologically, the hair follicles had been replaced by a strange coil of fibrous tissue. Some of these follicular sites showed ossification so prominent as to be evident in soft tissue reoentgenograms. In this patient, the skin itself showed a fibrous dysplasia analogous to that which has always been identified as occurring within the bones in Albright disease. In her skin, it is the hair follicle that is the site of this dysplasia. The appearance of ossification in the skin and fibrous dysplasia in the bone would seem to demonstrate a delicate equilibrial balance between fibrous and osteal tissue in organs of a common mesenchymal origin. Localized connective tissue stromal dysplasia is believed to play a role in the pathogenesis of not only the bony, but aslo the pigmentary and endocrine abnormalities of the disease."} {"id": "PMID:1275536", "title": "Rapid assessment of gestational age at birth.", "content": "A simple scoring system based on skin colour, skin texture, breast development, and ear firmness that can be performed even in an ill baby without manipulation or movement enables gestational age to be estimated to within +/- 15 days (95% confidence limits) at any time in the first 2 days of life. More complex techniques only marginally improve this estimate.", "contents": "Rapid assessment of gestational age at birth. A simple scoring system based on skin colour, skin texture, breast development, and ear firmness that can be performed even in an ill baby without manipulation or movement enables gestational age to be estimated to within +/- 15 days (95% confidence limits) at any time in the first 2 days of life. More complex techniques only marginally improve this estimate."} {"id": "PMID:1275537", "title": "Value of brain biopsy in neurodegenerative disease in childhood.", "content": "During the period 1968-1974, 45 children with suspected neurodegenerative syndromes underwent brain biopsy of the right frontal lobe. The histological examination was normal in 44% and nonspecifically abnormal in 43% of the specimens. In 13% a specific histological abnormality was found, namely 3 with spongy degeneration, 1 Alexander's leucodystrophy, 1 metachromatic leucodystrophy, and 1 pachygyria. Chemical analysis by thin-layer chromatography had little to offer in this series, being specifically abnormal only in the case of metachromatic leucodystrophy and nonspecifically abnormal in 6 cases. Postoperative generalized convulsions occurred in 3 children and a mild hemiparesis contralateral to the site of biopsy was noted in one patient. Comparing the outcome of the group having histologically normal biopsies with the group having nonspecifically abnormal ones it is concluded that frontal biopsy is not of such high prognostic value as has been claimed in previous reports. Some flexibility in the choice of the biopsy site is suggested. The specimens should be examined by chemical analysis as well as electron microscope in addition to the routine histological and histochemical methods. The neurodegenerative disorders of childhood which are at present identifiable in life only by brain biopsy are listed.", "contents": "Value of brain biopsy in neurodegenerative disease in childhood. During the period 1968-1974, 45 children with suspected neurodegenerative syndromes underwent brain biopsy of the right frontal lobe. The histological examination was normal in 44% and nonspecifically abnormal in 43% of the specimens. In 13% a specific histological abnormality was found, namely 3 with spongy degeneration, 1 Alexander's leucodystrophy, 1 metachromatic leucodystrophy, and 1 pachygyria. Chemical analysis by thin-layer chromatography had little to offer in this series, being specifically abnormal only in the case of metachromatic leucodystrophy and nonspecifically abnormal in 6 cases. Postoperative generalized convulsions occurred in 3 children and a mild hemiparesis contralateral to the site of biopsy was noted in one patient. Comparing the outcome of the group having histologically normal biopsies with the group having nonspecifically abnormal ones it is concluded that frontal biopsy is not of such high prognostic value as has been claimed in previous reports. Some flexibility in the choice of the biopsy site is suggested. The specimens should be examined by chemical analysis as well as electron microscope in addition to the routine histological and histochemical methods. The neurodegenerative disorders of childhood which are at present identifiable in life only by brain biopsy are listed."} {"id": "PMID:1275538", "title": "Menkes's steely hair syndrome.", "content": "Three unrelated cases of Menkes's syndrome are described. In addition to the typical features these cases all showed abnormalities of the urinary tract characterized by hydronephrosis, hydroureter, and bladder diverticula. There was no organic obstruction in the urinary tract and the changes are presumed to be due to disturbed innervation. The 3 patients showed no overall clinical response to parenteral copper therapy administered for periods of 1 to 8 months. Necropsy studies showed structural changes in veins as well as arteries together with aneurysm formation in both, and one case showed a polypoid lesion in the stomach.", "contents": "Menkes's steely hair syndrome. Three unrelated cases of Menkes's syndrome are described. In addition to the typical features these cases all showed abnormalities of the urinary tract characterized by hydronephrosis, hydroureter, and bladder diverticula. There was no organic obstruction in the urinary tract and the changes are presumed to be due to disturbed innervation. The 3 patients showed no overall clinical response to parenteral copper therapy administered for periods of 1 to 8 months. Necropsy studies showed structural changes in veins as well as arteries together with aneurysm formation in both, and one case showed a polypoid lesion in the stomach."} {"id": "PMID:1275539", "title": "Criteria for diagnosis of temporary gluten intolerance.", "content": "Strict criteria for the diagnosis of temporary gluten intolerance are formulated in the light of the case of an 8-week-old infant with severe diarrhoea and failure to thrive, who recovered on an elimination diet that was gluten-free. 8 weeks later an oral challenge with 2.5 g twice daily of powdered gluten for one day produced diarrhoea, weight loss, and impaired xylose absorption. Gluten was successfully reintroduced into the diet 9 months later without incident. Jejunal histology remains normal after 26 months of a daily diet that contains 5 to 10 g gluten.", "contents": "Criteria for diagnosis of temporary gluten intolerance. Strict criteria for the diagnosis of temporary gluten intolerance are formulated in the light of the case of an 8-week-old infant with severe diarrhoea and failure to thrive, who recovered on an elimination diet that was gluten-free. 8 weeks later an oral challenge with 2.5 g twice daily of powdered gluten for one day produced diarrhoea, weight loss, and impaired xylose absorption. Gluten was successfully reintroduced into the diet 9 months later without incident. Jejunal histology remains normal after 26 months of a daily diet that contains 5 to 10 g gluten."} {"id": "PMID:1275540", "title": "Respiratory complications in long-term survivors of oesophageal atresia.", "content": "One hundred of the 192 survivors of repaired oesophageal atresia at the Royal Children's Hospital, Melbourne, aged one year and over on 1 November 1973, were reviewed to determine the frequency of respiratory complications. 78 children suffered from more than 3 attacks of bronchitis per year during the first 3 years of life and 48% of the children aged over 8 years were having more than three attacks per year. Episodes of cough persisting longer than 2 weeks were also common. In the year preceding review, about half the children had more than 3 such episodes. 58 children had been admitted to hospital on at least one occasion for chest infection. It is suggested that recurrent inhalation of milk and food, consequent upon disordered oesophageal motility, is the major factor causing these respiratory complications.", "contents": "Respiratory complications in long-term survivors of oesophageal atresia. One hundred of the 192 survivors of repaired oesophageal atresia at the Royal Children's Hospital, Melbourne, aged one year and over on 1 November 1973, were reviewed to determine the frequency of respiratory complications. 78 children suffered from more than 3 attacks of bronchitis per year during the first 3 years of life and 48% of the children aged over 8 years were having more than three attacks per year. Episodes of cough persisting longer than 2 weeks were also common. In the year preceding review, about half the children had more than 3 such episodes. 58 children had been admitted to hospital on at least one occasion for chest infection. It is suggested that recurrent inhalation of milk and food, consequent upon disordered oesophageal motility, is the major factor causing these respiratory complications."} {"id": "PMID:1275541", "title": "Serum creatine phosphokinase in normal newborns.", "content": "Serum creatine phosphokinase (CPK) activity in 70 normal newborns was found to be significantly higher than the normal values found in adults or older children, and in some cases reached a level up to 10 times normal. It declined to near normal activity during the first 4 days and to normal level of activity by age 6-10 weeks. No clear correlation between birth trauma and increase in serum CPK activity was shown. CPK activity in cord blood was lower than in venous and capillary blood. Because of the increased CPK activity found in normal newborns, screening for Duchenne-type muscular dystrophy should be postponed for a few weeks after delivery.", "contents": "Serum creatine phosphokinase in normal newborns. Serum creatine phosphokinase (CPK) activity in 70 normal newborns was found to be significantly higher than the normal values found in adults or older children, and in some cases reached a level up to 10 times normal. It declined to near normal activity during the first 4 days and to normal level of activity by age 6-10 weeks. No clear correlation between birth trauma and increase in serum CPK activity was shown. CPK activity in cord blood was lower than in venous and capillary blood. Because of the increased CPK activity found in normal newborns, screening for Duchenne-type muscular dystrophy should be postponed for a few weeks after delivery."} {"id": "PMID:1275542", "title": "Modification to single catheter exchange transfusion technique.", "content": "A simple modification to the standard 'in-out' exchange transfusion technique is described which requires cannulation of the umbilical vein only, yet provides many of the theoretical and practical advantages of a 2-catheter arteriovenous technique. The advantages include a reduction of cardiovascular disturbance; a reduction of the inevitable pressure changes in the portal venous system (probably important in the pathogenesis of complicating necrotizing enterocolitis); administration of alkali or drugs diluted in donor blood; accurate assessment of balance; a more efficient exchange; and general ease of management allowing better clinical observation of the infant.", "contents": "Modification to single catheter exchange transfusion technique. A simple modification to the standard 'in-out' exchange transfusion technique is described which requires cannulation of the umbilical vein only, yet provides many of the theoretical and practical advantages of a 2-catheter arteriovenous technique. The advantages include a reduction of cardiovascular disturbance; a reduction of the inevitable pressure changes in the portal venous system (probably important in the pathogenesis of complicating necrotizing enterocolitis); administration of alkali or drugs diluted in donor blood; accurate assessment of balance; a more efficient exchange; and general ease of management allowing better clinical observation of the infant."} {"id": "PMID:1275543", "title": "Mortality in juvenile diabetes mellitus over 25 years.", "content": "Deaths over the past 25 years associated with diabetes mellitus under the age of 15 years are reviewed. Information is derived from the Registrar General's figures for England and Wales and from the records of a large paediatric diabetic unit.", "contents": "Mortality in juvenile diabetes mellitus over 25 years. Deaths over the past 25 years associated with diabetes mellitus under the age of 15 years are reviewed. Information is derived from the Registrar General's figures for England and Wales and from the records of a large paediatric diabetic unit."} {"id": "PMID:1275544", "title": "Cystic fibrosis screening in the newborn.", "content": "A new technique of measuring stool enzyme activity on dry specimens of faeces from newborn children at 4-5 days of age has detected 3 cases of cystic fibrosis in the first 6000 tests. No known cases of cystic fibrosis have been missed. Additionally, one case of pancreatic achylia of at least 4 months' duration has been detected. It is proposed that the detection of cystic fibrosis by this technique is sufficiently practical to be acceptable as a worthwhile newborn screening programme. The screening test has been in use in Auckland for over a year and is now being set up in Hamilton, Wellington, and Dunedin (New Zealand), and Sydney (Australia).", "contents": "Cystic fibrosis screening in the newborn. A new technique of measuring stool enzyme activity on dry specimens of faeces from newborn children at 4-5 days of age has detected 3 cases of cystic fibrosis in the first 6000 tests. No known cases of cystic fibrosis have been missed. Additionally, one case of pancreatic achylia of at least 4 months' duration has been detected. It is proposed that the detection of cystic fibrosis by this technique is sufficiently practical to be acceptable as a worthwhile newborn screening programme. The screening test has been in use in Auckland for over a year and is now being set up in Hamilton, Wellington, and Dunedin (New Zealand), and Sydney (Australia)."} {"id": "PMID:1275545", "title": "Thyrotoxicosis in a neonate of a mother with no history of thyroid disease.", "content": "A newborn infant had rectal prolapse, congenital lactase deficiency, and temporary neonatal thyrotoxicosis. The thyrotoxicosis was associated with a raised long-acting thyroid stimulator index in a mother with no personal or family history of thyroid or related autoimmune disease. The parents were first cousins.", "contents": "Thyrotoxicosis in a neonate of a mother with no history of thyroid disease. A newborn infant had rectal prolapse, congenital lactase deficiency, and temporary neonatal thyrotoxicosis. The thyrotoxicosis was associated with a raised long-acting thyroid stimulator index in a mother with no personal or family history of thyroid or related autoimmune disease. The parents were first cousins."} {"id": "PMID:1275546", "title": "Problems in anlysis of faecal sugar.", "content": "Significant amounts of sugar were found in 22% of 180 faecal samples from 135 children with acute or chronic diarrhoea. The methods used were the Clinitest method and paper chromatography. There was very good correlation between the results of these methods. Screening by Ph was less reliable. Various di- and monosaccharides were found. However, a disaccharide was never found without the simultaneous finding of its component monosaccharides. In vitro studies showed that the faecal flora has the ability to split disaccharides very rapidly. Within a few minutes much of the disaccharide had been split and no traces could be found after 30 minutes. Since the same process is assumed to take place in the lower gut, children with disacchardase deficency cannot be expected to excrete disaccharide alone in their faeces without the corresponding monosaccharides. The lack of a disaccharide in the faeces does not exclude the possibility of disaccharidase deficiency. Acid hydrolysis of faecal samples in cases of suspected sucrase deficiency seems not to be necessary.", "contents": "Problems in anlysis of faecal sugar. Significant amounts of sugar were found in 22% of 180 faecal samples from 135 children with acute or chronic diarrhoea. The methods used were the Clinitest method and paper chromatography. There was very good correlation between the results of these methods. Screening by Ph was less reliable. Various di- and monosaccharides were found. However, a disaccharide was never found without the simultaneous finding of its component monosaccharides. In vitro studies showed that the faecal flora has the ability to split disaccharides very rapidly. Within a few minutes much of the disaccharide had been split and no traces could be found after 30 minutes. Since the same process is assumed to take place in the lower gut, children with disacchardase deficency cannot be expected to excrete disaccharide alone in their faeces without the corresponding monosaccharides. The lack of a disaccharide in the faeces does not exclude the possibility of disaccharidase deficiency. Acid hydrolysis of faecal samples in cases of suspected sucrase deficiency seems not to be necessary."} {"id": "PMID:1275547", "title": "Effect of gestational length on albumin content of meconium.", "content": "During a screening programme for the detection of CF using the meconium albumin technique, the overall false-positive rate was found to be approximately 1%. When the gestational age of the infants was taken into account the false-positive rate was found to be significantly higher in preterm (8%) as compared to term infants (0.55%). This was due largely but not solely to the presence of occult blood. Possible explanations for these findings are discussed and attention drawn to the limitation of meconium albumin content as a screening technique for CF in preterm infants.", "contents": "Effect of gestational length on albumin content of meconium. During a screening programme for the detection of CF using the meconium albumin technique, the overall false-positive rate was found to be approximately 1%. When the gestational age of the infants was taken into account the false-positive rate was found to be significantly higher in preterm (8%) as compared to term infants (0.55%). This was due largely but not solely to the presence of occult blood. Possible explanations for these findings are discussed and attention drawn to the limitation of meconium albumin content as a screening technique for CF in preterm infants."} {"id": "PMID:1275550", "title": "Chrysanthemum allergy III. Identification of the allergens.", "content": "Experimental and chemical studies in guinea pigs on contact allergy caused by Chrysanthemum indicum L. (Chrysanthemum of the florists) led to the isolation of several sesquiterpene lactones. From the crude extract of dried flowers 12 fractions were obtained of which four gave strong reactions on epicutaneous application to guinea pigs sensitized with an extract of C. indicum L. One of these allergens was identified as a sesquiterpene lactone of the guaianolide type. It is identical to Arteglasin-A derived from Artemisia douglasiana Bess. The occurrence of Arteglasin-A in Chrysanthemum indicum L. as well as its allergenic properties are described forthe first time. These findings give rise to the assumption that the other, as yet unidentified sesquiterpene lactones of this flower also belong to the guaianolide type.", "contents": "Chrysanthemum allergy III. Identification of the allergens. Experimental and chemical studies in guinea pigs on contact allergy caused by Chrysanthemum indicum L. (Chrysanthemum of the florists) led to the isolation of several sesquiterpene lactones. From the crude extract of dried flowers 12 fractions were obtained of which four gave strong reactions on epicutaneous application to guinea pigs sensitized with an extract of C. indicum L. One of these allergens was identified as a sesquiterpene lactone of the guaianolide type. It is identical to Arteglasin-A derived from Artemisia douglasiana Bess. The occurrence of Arteglasin-A in Chrysanthemum indicum L. as well as its allergenic properties are described forthe first time. These findings give rise to the assumption that the other, as yet unidentified sesquiterpene lactones of this flower also belong to the guaianolide type."} {"id": "PMID:1275551", "title": "[Accident in treatment of porphyria cutanea tarda by chloroquine (Resochin) (author's transl)].", "content": "About a 65-year old patient with the typical clinical and biochemical characteristics of porphyria cutanea tarda (Pct) is reported. After treatment with Resochin in an erroneously high dosage (1.250 mg instead of 125 mg) an acute crisis set in with a triple increase of porphyrin excretion, fever, tachycardia, hypertension and joint-discomfort. Despite the rise in excretion of total porphyrines in urine to approximately 18.00 mcg/l there was no change in the amount of the porphyrin precursors (ALA, PBG). The pattern of the porphyrin-metabolites (URO-, HEPTA,- HEXA-, PENTA-, COPRO-porphyrin)-expressed in rel.%-does not change during the excessive rise of porphyrin excretion. The duration Resochin-therapy could obviously not be shortened by an initial too high dosage of chloroquine. The mechanism of action of chloroquine in Pct is not clear. It is discussed that a change in the permeability of the liver mitochondria leads to a continuously increased excretion of porphyrin and to an exhaustion of the hepatic porphyrin pool.", "contents": "[Accident in treatment of porphyria cutanea tarda by chloroquine (Resochin) (author's transl)]. About a 65-year old patient with the typical clinical and biochemical characteristics of porphyria cutanea tarda (Pct) is reported. After treatment with Resochin in an erroneously high dosage (1.250 mg instead of 125 mg) an acute crisis set in with a triple increase of porphyrin excretion, fever, tachycardia, hypertension and joint-discomfort. Despite the rise in excretion of total porphyrines in urine to approximately 18.00 mcg/l there was no change in the amount of the porphyrin precursors (ALA, PBG). The pattern of the porphyrin-metabolites (URO-, HEPTA,- HEXA-, PENTA-, COPRO-porphyrin)-expressed in rel.%-does not change during the excessive rise of porphyrin excretion. The duration Resochin-therapy could obviously not be shortened by an initial too high dosage of chloroquine. The mechanism of action of chloroquine in Pct is not clear. It is discussed that a change in the permeability of the liver mitochondria leads to a continuously increased excretion of porphyrin and to an exhaustion of the hepatic porphyrin pool."} {"id": "PMID:1275552", "title": "Investigative studies of the dermatitis caused by the larva of the brown-tail moth (Euproctis chrysorrhoea Linn.) II. Histopathology of skin lesions and scanning electron microscopy of their causative setae.", "content": "Two different aspects related to the dermatitis caused by the so-called nettling hairs of the larva of the brown-tail moth, Euproctis chrysorrhoea L., are documented. The first part describes the sequence of histopathologic changes associated with the inflammatory process in the human skin induced by epicutaneous application untreated (UT-N) and heat treated (HT-N) nettling hairs. The penetration of untreated and heat treated nettling hairs into the epidermis is evident from their presence in 12 out of 29 UT-N lesions and 5 out of 10 HT-N lesions respectively. The introduction of nettling hairs into the skin leads to damage and bulla formation of the surface epithelium and early inflammatory signs consisting of edematous changes of the dermis and pervascular infiltration of neutrophils, eosinophils and mononuclear leucocytes. After few hours the intensity of the dermal infiltrate has increased and spongiotic changes appear. After 48--72 h the perivascular infiltrate is mainly composed of mononuclear cells, while along with increased spongiosis the damaged surface epithelium may show repair. The traumatic changes of the surface epithelium in HT-N lesions appear less prominent in comparison with the UT-N lesions. The second part describes the findings obtained by scanning electron microscopy of the nettling hairs. Evidence is brought forward to support the view that the offending setae may be looked upon as tapering, hollow microcapillaries which are open at both ends. The present findings are consistent with the idea that the nettling hairs may serve as microneedles from which irritant substances may be liberated when penetrating into the skin, and that the resulting inflammatory reactions are attributable to combined mechanical and toxic effects.", "contents": "Investigative studies of the dermatitis caused by the larva of the brown-tail moth (Euproctis chrysorrhoea Linn.) II. Histopathology of skin lesions and scanning electron microscopy of their causative setae. Two different aspects related to the dermatitis caused by the so-called nettling hairs of the larva of the brown-tail moth, Euproctis chrysorrhoea L., are documented. The first part describes the sequence of histopathologic changes associated with the inflammatory process in the human skin induced by epicutaneous application untreated (UT-N) and heat treated (HT-N) nettling hairs. The penetration of untreated and heat treated nettling hairs into the epidermis is evident from their presence in 12 out of 29 UT-N lesions and 5 out of 10 HT-N lesions respectively. The introduction of nettling hairs into the skin leads to damage and bulla formation of the surface epithelium and early inflammatory signs consisting of edematous changes of the dermis and pervascular infiltration of neutrophils, eosinophils and mononuclear leucocytes. After few hours the intensity of the dermal infiltrate has increased and spongiotic changes appear. After 48--72 h the perivascular infiltrate is mainly composed of mononuclear cells, while along with increased spongiosis the damaged surface epithelium may show repair. The traumatic changes of the surface epithelium in HT-N lesions appear less prominent in comparison with the UT-N lesions. The second part describes the findings obtained by scanning electron microscopy of the nettling hairs. Evidence is brought forward to support the view that the offending setae may be looked upon as tapering, hollow microcapillaries which are open at both ends. The present findings are consistent with the idea that the nettling hairs may serve as microneedles from which irritant substances may be liberated when penetrating into the skin, and that the resulting inflammatory reactions are attributable to combined mechanical and toxic effects."} {"id": "PMID:1275553", "title": "[Structural changes of the basement tubule membrane in the so-called Sertoli cell syndrome (author's transl)].", "content": "In the so-called Sertoli cell syndrome nearly always club shaped invaginations of the basement tubule membrane with intact cellule membrane can be seen. These protuberatons ultrastructurally prove to be multiplicated piles of the lamina densa of the basement membrane. The cells in the Sertoli cell syndrome show a quantitatively and qualitatively reduced pattern of enzymes in contrast with the active Sertoli cells.", "contents": "[Structural changes of the basement tubule membrane in the so-called Sertoli cell syndrome (author's transl)]. In the so-called Sertoli cell syndrome nearly always club shaped invaginations of the basement tubule membrane with intact cellule membrane can be seen. These protuberatons ultrastructurally prove to be multiplicated piles of the lamina densa of the basement membrane. The cells in the Sertoli cell syndrome show a quantitatively and qualitatively reduced pattern of enzymes in contrast with the active Sertoli cells."} {"id": "PMID:1275554", "title": "[Cellular immunity in melanomalignome (author's transl)].", "content": "Cellular immunological reactivity was examined in 20 patients having melanomalignoma at different clinical stages, using Leukocyte-Migration-Inhibition-Test. As antigens three homologous melanoma-extracts were used, produced by our own method. Independent from the clinical stages cell-migration inhibition could be established in 15 out of the 20 patients. In this way, these tumor extracts have been shown to contain melanoma-associated antigens. Regardless of the clinical stage of the disease, the melanomalignomas patient produces cellular immunity against those tumor-antigens. It is note-worthy that the actual course of the disease seems not to be influenced by immun-mechanisms.", "contents": "[Cellular immunity in melanomalignome (author's transl)]. Cellular immunological reactivity was examined in 20 patients having melanomalignoma at different clinical stages, using Leukocyte-Migration-Inhibition-Test. As antigens three homologous melanoma-extracts were used, produced by our own method. Independent from the clinical stages cell-migration inhibition could be established in 15 out of the 20 patients. In this way, these tumor extracts have been shown to contain melanoma-associated antigens. Regardless of the clinical stage of the disease, the melanomalignomas patient produces cellular immunity against those tumor-antigens. It is note-worthy that the actual course of the disease seems not to be influenced by immun-mechanisms."} {"id": "PMID:1275555", "title": "Lung cancer following exposure to chloromethyl methyl ether. An epidemiological study.", "content": "A historical prospective epidemiological study was conducted on workers exposed to chloromethyl methyl ether (CMME) containing 0.5% to 4% bis(chloromethyl) ether (BCME) as an impurity. The study period was 1948 to 1972. Follow-up procedures located 98.9% of the cohort, including those separated from the plant. The cause of death was established for 95.3% of the 278 known deceased men. A CMME exposure rating system was established from employees' work histories and recollections of supervisors. This system approximated relative exposure concentrations and duration times. Analysis on an age-specific basis revealed a relative risk of lung cancer 3.8 times higher in 669 exposed vs 1,616 unexposed workers, a significant increase. Although limited by lack of quantitative environmental sampling data, dose-response relationships were established between lung cancer an intensity and/or duration of exposure.", "contents": "Lung cancer following exposure to chloromethyl methyl ether. An epidemiological study. A historical prospective epidemiological study was conducted on workers exposed to chloromethyl methyl ether (CMME) containing 0.5% to 4% bis(chloromethyl) ether (BCME) as an impurity. The study period was 1948 to 1972. Follow-up procedures located 98.9% of the cohort, including those separated from the plant. The cause of death was established for 95.3% of the 278 known deceased men. A CMME exposure rating system was established from employees' work histories and recollections of supervisors. This system approximated relative exposure concentrations and duration times. Analysis on an age-specific basis revealed a relative risk of lung cancer 3.8 times higher in 669 exposed vs 1,616 unexposed workers, a significant increase. Although limited by lack of quantitative environmental sampling data, dose-response relationships were established between lung cancer an intensity and/or duration of exposure."} {"id": "PMID:1275556", "title": "Respiratory tract deposition of smoke particles using a nasal bypass device.", "content": "In order to avoid nasal absorption, an intralaryngeal cannula was tested as a device for bypassing the nose in delivering smoke into the lungs of hamsters. The intralaryngeal cannula increased lung deposition of radiolabeled smoke particles twofold to threefold over that in nose-breathing controls. Stabilization of respiration (absence of avoidance reaction), rather than prevention of nasal absorption of smoke, was demonstrated to be the cannula's major mechanism of action. Although suitable for acute exposures, the device is of limited use for chronic exposures that require daily insertion of the cannula during an extended period of time.", "contents": "Respiratory tract deposition of smoke particles using a nasal bypass device. In order to avoid nasal absorption, an intralaryngeal cannula was tested as a device for bypassing the nose in delivering smoke into the lungs of hamsters. The intralaryngeal cannula increased lung deposition of radiolabeled smoke particles twofold to threefold over that in nose-breathing controls. Stabilization of respiration (absence of avoidance reaction), rather than prevention of nasal absorption of smoke, was demonstrated to be the cannula's major mechanism of action. Although suitable for acute exposures, the device is of limited use for chronic exposures that require daily insertion of the cannula during an extended period of time."} {"id": "PMID:1275557", "title": "Studies of respiratory morbidity in rubber workers. Part III. Respiratory morbidity in processing workers.", "content": "Respiratory questionnaires and pulmonary function tests were administered to sixty-five men exposed to dust in the processing are from three rubber tire manufacturing plants. Similar tests were done on 189 \"control\" workers. Compared with the controls, the processing workers had a higher prevalence of chronic productive cough. Overall, the processing group showed a decrease in the ratio of FEV to FVC. The processing workers with more than ten years of exposure showed a significant decrease in the ratio of FEV1.0/FVC, the FEV1.0, the residual FEV1.0, and the flow rates at 50% and 25% of the forced vital capacity. None of the pulmonary function effects could be solely explained on the basis of smoking, age, ethnic, or socioeconomic factors: all were related to the length of exposure. Based on these results we conclude that exposure in the processing area produces pulmonary disease.", "contents": "Studies of respiratory morbidity in rubber workers. Part III. Respiratory morbidity in processing workers. Respiratory questionnaires and pulmonary function tests were administered to sixty-five men exposed to dust in the processing are from three rubber tire manufacturing plants. Similar tests were done on 189 \"control\" workers. Compared with the controls, the processing workers had a higher prevalence of chronic productive cough. Overall, the processing group showed a decrease in the ratio of FEV to FVC. The processing workers with more than ten years of exposure showed a significant decrease in the ratio of FEV1.0/FVC, the FEV1.0, the residual FEV1.0, and the flow rates at 50% and 25% of the forced vital capacity. None of the pulmonary function effects could be solely explained on the basis of smoking, age, ethnic, or socioeconomic factors: all were related to the length of exposure. Based on these results we conclude that exposure in the processing area produces pulmonary disease."} {"id": "PMID:1275559", "title": "Increased life span and decreased weight in hamsters exposed to cigarette smoke.", "content": "Five groups of fifty-one 2-month-old male Syrian golden hamsters received three 10-minute exposures to cigarette smoke per day, 5 days per week, for the duration of their lives. Three of the groups were also chronically exposed to aerosols of chrysotile asbestos, cobalt oxide, and nickel oxides, respectively. The fourth group received twelve weekly injections of 0.25 mg of diethylnitrosamine. The smoke-exposed groups lived significantly (P less than .01) longer than their sham-exposed cohorts and untreated controls. Their mean body weights were significantly (P less than .01) lower than in the sham-exposed groups. The hypothesis is proposed that delayed onset of amyloidosis and lower body weight in the smoke-exposed hamsters may have been responsible for their increased life spans. It is hypothesized that cigarette smoke affected the immune system of the animals, resulting in retardation of amyloidosis, a frequent cause of death in hamsters.", "contents": "Increased life span and decreased weight in hamsters exposed to cigarette smoke. Five groups of fifty-one 2-month-old male Syrian golden hamsters received three 10-minute exposures to cigarette smoke per day, 5 days per week, for the duration of their lives. Three of the groups were also chronically exposed to aerosols of chrysotile asbestos, cobalt oxide, and nickel oxides, respectively. The fourth group received twelve weekly injections of 0.25 mg of diethylnitrosamine. The smoke-exposed groups lived significantly (P less than .01) longer than their sham-exposed cohorts and untreated controls. Their mean body weights were significantly (P less than .01) lower than in the sham-exposed groups. The hypothesis is proposed that delayed onset of amyloidosis and lower body weight in the smoke-exposed hamsters may have been responsible for their increased life spans. It is hypothesized that cigarette smoke affected the immune system of the animals, resulting in retardation of amyloidosis, a frequent cause of death in hamsters."} {"id": "PMID:1275558", "title": "Morbidity studies of workers exposed to whole body vibration.", "content": "Insurance claims for medical services submitted on behalf of a group of workers in the construction industry were collected over a 20-month period. The morbidity experience of those workers exposed to whole body vibration was contrasted with that of an unexposed control group eligible for benefits under the same plan. Using Mantel-Haenszel adjustment for age and experience, a significantly elevated relative risk was found among the exposed group in three of the thirty disease categories studied. In no disease category did the control group possess a significantly higher risk of requiring medical services. A striking proportion of the disease categories showed an initial increase in risk for exposed workers followed by a decrease with experience. This pattern suggests a selection process in which workers leave exposed-group jobs as they become afflicted with certain disease conditions.", "contents": "Morbidity studies of workers exposed to whole body vibration. Insurance claims for medical services submitted on behalf of a group of workers in the construction industry were collected over a 20-month period. The morbidity experience of those workers exposed to whole body vibration was contrasted with that of an unexposed control group eligible for benefits under the same plan. Using Mantel-Haenszel adjustment for age and experience, a significantly elevated relative risk was found among the exposed group in three of the thirty disease categories studied. In no disease category did the control group possess a significantly higher risk of requiring medical services. A striking proportion of the disease categories showed an initial increase in risk for exposed workers followed by a decrease with experience. This pattern suggests a selection process in which workers leave exposed-group jobs as they become afflicted with certain disease conditions."} {"id": "PMID:1275561", "title": "Mercury and selenium distribution in a defined area and in its population.", "content": "In the Amiata Mountain area of Tuscany, Italy, a survey has examined the concentrations of mercury and selenium in the environment, in the food chain, and in human biological samples of blood, urine, and hair. This area was selected for study because of its large mineral deposits and concentration of elements, e.g., iron, copper, silver, antimony, and particularly mercury. Subjects consisted of a group with high occupational exposure to mercury vapor, a group randomly exposed to mercury dust, and a group nonoccupationally exposed to mercury. The selenium and mercury contents in all samples were determined by nondestructive neutron activation analysis, and results showed that the human metabolism of mercury is different from that of selenium and that the selenium retention in man could be influenced by the mercury intake. Furthermore, a great part of selenium introduced through the diet passes into the blood, where it is mainly associated with blood cells.", "contents": "Mercury and selenium distribution in a defined area and in its population. In the Amiata Mountain area of Tuscany, Italy, a survey has examined the concentrations of mercury and selenium in the environment, in the food chain, and in human biological samples of blood, urine, and hair. This area was selected for study because of its large mineral deposits and concentration of elements, e.g., iron, copper, silver, antimony, and particularly mercury. Subjects consisted of a group with high occupational exposure to mercury vapor, a group randomly exposed to mercury dust, and a group nonoccupationally exposed to mercury. The selenium and mercury contents in all samples were determined by nondestructive neutron activation analysis, and results showed that the human metabolism of mercury is different from that of selenium and that the selenium retention in man could be influenced by the mercury intake. Furthermore, a great part of selenium introduced through the diet passes into the blood, where it is mainly associated with blood cells."} {"id": "PMID:1275560", "title": "Hypoxia and induced mutations in Syrian (golden) hamsters. The origin and perpetuation of a species.", "content": "We were able to identify anomalous chromosome patterns-monosomy, trisomy, and polyploidy-in metaphase plates prepared from embryos of Syrian hamsters (Mesocricetus auratus) whose mothers had been exposed to low-pressure hypoxia during the hours after copulation. These females were exposed in a low-pressure chamber for 4 hours at pressures equivalent to 30,000 feet of altitude before (estimated) ovulation to create acid shifts of pH equilibrium in the milieu of newly released eggs during passage of sperm upward, during fertilization itself, and during early cleavage stages. The D group chromosomes were most frequently involved in both monosomy and hyperdiploidy. The easily identifiable X chromosome also appeared to be susceptible to aneuploid formation. Chromosomally abnormal patterns most frequently among sibling embryos conceived by aging mothers exposed to low-pressure hypoxia. The significance of induced mutations is discussed.", "contents": "Hypoxia and induced mutations in Syrian (golden) hamsters. The origin and perpetuation of a species. We were able to identify anomalous chromosome patterns-monosomy, trisomy, and polyploidy-in metaphase plates prepared from embryos of Syrian hamsters (Mesocricetus auratus) whose mothers had been exposed to low-pressure hypoxia during the hours after copulation. These females were exposed in a low-pressure chamber for 4 hours at pressures equivalent to 30,000 feet of altitude before (estimated) ovulation to create acid shifts of pH equilibrium in the milieu of newly released eggs during passage of sperm upward, during fertilization itself, and during early cleavage stages. The D group chromosomes were most frequently involved in both monosomy and hyperdiploidy. The easily identifiable X chromosome also appeared to be susceptible to aneuploid formation. Chromosomally abnormal patterns most frequently among sibling embryos conceived by aging mothers exposed to low-pressure hypoxia. The significance of induced mutations is discussed."} {"id": "PMID:1275563", "title": "Reducing sample sizes when comparing experimental and control groups.", "content": "In comparing rates for two groups (one control and the other experimental), one may use an historical control to reduce the sample size needed for a test of significance to one-fourth that required if the control is not historical. If there is some doubt as to whether one's control is comparable to the historical control, a test showing the equality of the historical and experimental controls can lead to a halving of the sample required for significance testing. This same argument also applies to the comparison of two means.", "contents": "Reducing sample sizes when comparing experimental and control groups. In comparing rates for two groups (one control and the other experimental), one may use an historical control to reduce the sample size needed for a test of significance to one-fourth that required if the control is not historical. If there is some doubt as to whether one's control is comparable to the historical control, a test showing the equality of the historical and experimental controls can lead to a halving of the sample required for significance testing. This same argument also applies to the comparison of two means."} {"id": "PMID:1275562", "title": "Management of acute sulfide poisoning. Effects of oxygen, thiosulfate, and nitrite.", "content": "Oxygen (100% at 1 atmosphere) did not protect mice against death from acute sulfide poisoning as compared with animals maintained under air at 1 atmosphere. Sodium thiosulfate had a small, but statistically significant (P less than .05) protective effect against death due to sodium sulfide, whether the mice were maintained under air or oxygen. Pretreatment with sodium nitrite, however, increased the acute intraperitoneal lethal dose for 50% survival of the group (LD50) of sodium sulfide 2.5 times. Neither oxygen, thiosulfate, nor the combination potentiated the protective effects of nitrite against sulfide poisoning. Antidotal effects of nitrite in acute sulfide poisoning were demonstrated in rats. The therapeutic efficacy of nitrite in acute poisoning is clearly superior to that of oxygen, which is the more widely recommended antidote.", "contents": "Management of acute sulfide poisoning. Effects of oxygen, thiosulfate, and nitrite. Oxygen (100% at 1 atmosphere) did not protect mice against death from acute sulfide poisoning as compared with animals maintained under air at 1 atmosphere. Sodium thiosulfate had a small, but statistically significant (P less than .05) protective effect against death due to sodium sulfide, whether the mice were maintained under air or oxygen. Pretreatment with sodium nitrite, however, increased the acute intraperitoneal lethal dose for 50% survival of the group (LD50) of sodium sulfide 2.5 times. Neither oxygen, thiosulfate, nor the combination potentiated the protective effects of nitrite against sulfide poisoning. Antidotal effects of nitrite in acute sulfide poisoning were demonstrated in rats. The therapeutic efficacy of nitrite in acute poisoning is clearly superior to that of oxygen, which is the more widely recommended antidote."} {"id": "PMID:1275575", "title": "Preliminary observations on an isolate from synvoial fluid of patients with rheumatoid arthritis.", "content": "A very slow-growing micro-organism has been isolated from the synovial fluid of patients suffering from rheumatoid arthritis. This organism exhibits some of the properties of a mycoplasma such as growth in the presence of penicillin, and the requirement of serum and yeast, but generally does not behave like any known species of this group. Colonies resemble some types of T-mycoplasma in morphology and size. Scanning electron microscopy showed that the size of the components of these colonies was exceedingly small.", "contents": "Preliminary observations on an isolate from synvoial fluid of patients with rheumatoid arthritis. A very slow-growing micro-organism has been isolated from the synovial fluid of patients suffering from rheumatoid arthritis. This organism exhibits some of the properties of a mycoplasma such as growth in the presence of penicillin, and the requirement of serum and yeast, but generally does not behave like any known species of this group. Colonies resemble some types of T-mycoplasma in morphology and size. Scanning electron microscopy showed that the size of the components of these colonies was exceedingly small."} {"id": "PMID:1275576", "title": "Arthritis of mice induced by Mycoplasma arthritidis. Humoral antibody and lymphocyte responses of CBA mice.", "content": "Peak arthritis occurred 7 days after intravenous injection of CBA mice with Mycoplasma arthritidis and persisted in some animals for 84 days. A marked leucocytosis was apparent for the first 21 days. Complement-fixing antibodies reached a peak 14 days after injection of the organisms and persisted at high levels for 84 days. Metabolic-inhibiting and mycoplasmacidal antibodies were present but at much lower titres.", "contents": "Arthritis of mice induced by Mycoplasma arthritidis. Humoral antibody and lymphocyte responses of CBA mice. Peak arthritis occurred 7 days after intravenous injection of CBA mice with Mycoplasma arthritidis and persisted in some animals for 84 days. A marked leucocytosis was apparent for the first 21 days. Complement-fixing antibodies reached a peak 14 days after injection of the organisms and persisted at high levels for 84 days. Metabolic-inhibiting and mycoplasmacidal antibodies were present but at much lower titres."} {"id": "PMID:1275577", "title": "Thermoanalytical and histological study of intra-articular papain-induced degradation and repair of rabbit cartilage. II. Mature animals.", "content": "The effect of papain treatment on the cartilage tissue of the knee joint of mature rabbits was studied by histological and thermoanalytical methods. Changes taking place in the composition of cartilage in the course of ageing were shown. As a result of papain treatment a significant irreversible destruction of the ground substance took place. Papain-induced loss of proteoglycans and the intensity of repair reactions and age-related differences are discussed.", "contents": "Thermoanalytical and histological study of intra-articular papain-induced degradation and repair of rabbit cartilage. II. Mature animals. The effect of papain treatment on the cartilage tissue of the knee joint of mature rabbits was studied by histological and thermoanalytical methods. Changes taking place in the composition of cartilage in the course of ageing were shown. As a result of papain treatment a significant irreversible destruction of the ground substance took place. Papain-induced loss of proteoglycans and the intensity of repair reactions and age-related differences are discussed."} {"id": "PMID:1275578", "title": "Antibody-mediated leucocyte cytotoxicity to Chang human liver cells in rheumatoid arthritis and other diseases.", "content": "The incidence of an IgG-antibody which induces lymphocyte cytotoxicity to Chang human liver cells in culture was estimated in the sera of patients with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and in healthy controls. It was found in 4.1% of control subjects and in 31% of patients with rheumatoid arthritis. None of the other patient groups differed from the control group. This may be the first demonstration of an antibody response to an antigen or antigens which is almost entirely confined to patients with rheumatoid arthritis. The possibility that an antigenic similarity exists between the rheumatoid synovial membrane and Chang cells is currently under investigation.", "contents": "Antibody-mediated leucocyte cytotoxicity to Chang human liver cells in rheumatoid arthritis and other diseases. The incidence of an IgG-antibody which induces lymphocyte cytotoxicity to Chang human liver cells in culture was estimated in the sera of patients with rheumatoid arthritis, systemic lupus erythematosus, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, ulcerative colitis, and in healthy controls. It was found in 4.1% of control subjects and in 31% of patients with rheumatoid arthritis. None of the other patient groups differed from the control group. This may be the first demonstration of an antibody response to an antigen or antigens which is almost entirely confined to patients with rheumatoid arthritis. The possibility that an antigenic similarity exists between the rheumatoid synovial membrane and Chang cells is currently under investigation."} {"id": "PMID:1275579", "title": "Serum immunoreactive gastrin: specificity for rheumatoid arthritis, bimodality of distribution, and failure of effect of anti-inflammatory drugs.", "content": "A significant rise in immunoreactive gastrin in a proportion of patients with rheumatoid arthritis is confirmed. Such a rise does not seem to occur in other inflammatory or tissue destructive diseases. The patients with raised immunoreactive gastrin appear to form a separate population but the factors determining this separation remain obscure. Anti-inflammatory drugs, at least during short-term administration have no influence on immunoreactive gastrin concentrations.", "contents": "Serum immunoreactive gastrin: specificity for rheumatoid arthritis, bimodality of distribution, and failure of effect of anti-inflammatory drugs. A significant rise in immunoreactive gastrin in a proportion of patients with rheumatoid arthritis is confirmed. Such a rise does not seem to occur in other inflammatory or tissue destructive diseases. The patients with raised immunoreactive gastrin appear to form a separate population but the factors determining this separation remain obscure. Anti-inflammatory drugs, at least during short-term administration have no influence on immunoreactive gastrin concentrations."} {"id": "PMID:1275580", "title": "Early abnormalities of pisiform and triquetrum in rheumatoid arthritis.", "content": "Erosions on the triquetrum and pisiform are frequent in early rheumatoid arthritis and occur characteristically at 3 sites. (a) A shallow erosion on the proximal medial triquetral \"bare\" area is related to synovial proliferation at the margin of the radiocarpal cavity, although compressive forces from an adjacent long ulnar styloid may be contributory; (b) an erosive abnormality on the distal medial triquetrum is related to synovial proliferation along the margin of the midcarpal joint; and (c) ring-like erosions on apposing surfaces of the triquetrum and pisiform are produced by pannus within the pisiform-triquetral compartment.", "contents": "Early abnormalities of pisiform and triquetrum in rheumatoid arthritis. Erosions on the triquetrum and pisiform are frequent in early rheumatoid arthritis and occur characteristically at 3 sites. (a) A shallow erosion on the proximal medial triquetral \"bare\" area is related to synovial proliferation at the margin of the radiocarpal cavity, although compressive forces from an adjacent long ulnar styloid may be contributory; (b) an erosive abnormality on the distal medial triquetrum is related to synovial proliferation along the margin of the midcarpal joint; and (c) ring-like erosions on apposing surfaces of the triquetrum and pisiform are produced by pannus within the pisiform-triquetral compartment."} {"id": "PMID:1275581", "title": "Surface strain distribution in isolated single lumbar vertebrae.", "content": "The surface strains of isolated single lumbar vertebrae under compressive load were examined by the techniques of brittlecoat and photoelastic analysis. Directions of principal strain components have been determined. Areas of stress concentration were found around the vertebral rims, near the pedicles, and around the foramina of the basivertebral veins.", "contents": "Surface strain distribution in isolated single lumbar vertebrae. The surface strains of isolated single lumbar vertebrae under compressive load were examined by the techniques of brittlecoat and photoelastic analysis. Directions of principal strain components have been determined. Areas of stress concentration were found around the vertebral rims, near the pedicles, and around the foramina of the basivertebral veins."} {"id": "PMID:1275582", "title": "Lubrication of synovial membrane.", "content": "(1) An apparatus has been constructed to measure the coefficient of friction of synovial membrane against a glass slider. (2) Provision was made to vary the load on the specimens. (3) The coefficient of friction varied from 0-006 to 0-07. (4) A presentation similar to that used in the Sommerfeld analysis of journal bearings indicated that in these experiments synovial membrane was lubricated in the hydrodynamic regimen.", "contents": "Lubrication of synovial membrane. (1) An apparatus has been constructed to measure the coefficient of friction of synovial membrane against a glass slider. (2) Provision was made to vary the load on the specimens. (3) The coefficient of friction varied from 0-006 to 0-07. (4) A presentation similar to that used in the Sommerfeld analysis of journal bearings indicated that in these experiments synovial membrane was lubricated in the hydrodynamic regimen."} {"id": "PMID:1275583", "title": "Effect of yttrium 90 on experimental allergic arthritis in rabbits.", "content": "Seventeen rabbits were immunized with complete Freund's adjuvant and bovine serum albumin by the method of Dumonde and Glynn (1962), as modified by Cooke and Jasin (1972). Fifteen weeks after allergic arthritis developed in the knee joint, 8 animals were given an injection of 20 muCi yttrium 90 (90Y) into the left joint cavity; 7 were injected with 400 muCi. The animals were sacrificed at 2, 4, 8, 12, and 16 weeks and at 6 and 12 months after the injection. The right knee joint served as control for assessment of untreated allergic arthritis. Morphological control of the severity of the arthritis was provided by sacrificing 2 uninjected animals 13 weeks after immunization.", "contents": "Effect of yttrium 90 on experimental allergic arthritis in rabbits. Seventeen rabbits were immunized with complete Freund's adjuvant and bovine serum albumin by the method of Dumonde and Glynn (1962), as modified by Cooke and Jasin (1972). Fifteen weeks after allergic arthritis developed in the knee joint, 8 animals were given an injection of 20 muCi yttrium 90 (90Y) into the left joint cavity; 7 were injected with 400 muCi. The animals were sacrificed at 2, 4, 8, 12, and 16 weeks and at 6 and 12 months after the injection. The right knee joint served as control for assessment of untreated allergic arthritis. Morphological control of the severity of the arthritis was provided by sacrificing 2 uninjected animals 13 weeks after immunization."} {"id": "PMID:1275584", "title": "Single daily dose corticosteroid treatment.", "content": "Thirteen patients with rheumatoid or psoriatic arthritis who had not previously received corticosteroids were treated with prednisolone in a single-dose each morning. Insulin-hypoglycaemia tests were performed before starting steroids in each patient, and again at the conclusion of the study in twelve of the thirteen (duration of steroid treatment 8-40 m). There was no difference in the mean basal or peak levels of corticosteroids, or the mean peak of growth hormone (GH) in the tests done before or during treatment, although one patient lost GH responsiveness. There was thus no evidence of hypothalamo-pituitary-adrenal (HPA) suppression in any of the twelve patients, and there was a good therapeutic response in twelve out of thirteen. One patient was dropped from the trial because treatment failed. In contrast, of seven patients who had received a similar total dose of prednisolone twice daily, three showed HPA suppression and two had lost GH responsiveness.", "contents": "Single daily dose corticosteroid treatment. Thirteen patients with rheumatoid or psoriatic arthritis who had not previously received corticosteroids were treated with prednisolone in a single-dose each morning. Insulin-hypoglycaemia tests were performed before starting steroids in each patient, and again at the conclusion of the study in twelve of the thirteen (duration of steroid treatment 8-40 m). There was no difference in the mean basal or peak levels of corticosteroids, or the mean peak of growth hormone (GH) in the tests done before or during treatment, although one patient lost GH responsiveness. There was thus no evidence of hypothalamo-pituitary-adrenal (HPA) suppression in any of the twelve patients, and there was a good therapeutic response in twelve out of thirteen. One patient was dropped from the trial because treatment failed. In contrast, of seven patients who had received a similar total dose of prednisolone twice daily, three showed HPA suppression and two had lost GH responsiveness."} {"id": "PMID:1275585", "title": "Serum uric acid concentrations in a Xhosa community in the Transkei of Southern Africa.", "content": "Serum uric acid (SUA) concentrations were measured in specimens obtained from 479 respondents aged 15 and over during an epidemiological survey of bone and joint conditions in a tribal Xhosa community living in the Transkei, Southern Africa. Population SUA levels in the Xhosa were significantly lower than those previously observed in South Africa Negro groups in rural and urban environments. This finding agrees with the observations that population SUA concentrations tend to rise with increasing complexity of life style.", "contents": "Serum uric acid concentrations in a Xhosa community in the Transkei of Southern Africa. Serum uric acid (SUA) concentrations were measured in specimens obtained from 479 respondents aged 15 and over during an epidemiological survey of bone and joint conditions in a tribal Xhosa community living in the Transkei, Southern Africa. Population SUA levels in the Xhosa were significantly lower than those previously observed in South Africa Negro groups in rural and urban environments. This finding agrees with the observations that population SUA concentrations tend to rise with increasing complexity of life style."} {"id": "PMID:1275586", "title": "Objective measurement of rheumatoid arthritis using technetium index.", "content": "The technetium index was measured in 22 patients with rheumatoid arthritis, before and after 6 months' treatment either with penicillamine or with anti-inflammatory drugs. The index was calculated by dividing the sum of the count rates over both knees and both wrists by the dose of technetium given. In the penicillamine group there was a significant reduction in the technetium index and the changes correlated well with some clinical measurements of improvement. It is suggested that the technetium index is a useful objective measure of the effects of drugs with a specific activity in rheumatoid arthritis.", "contents": "Objective measurement of rheumatoid arthritis using technetium index. The technetium index was measured in 22 patients with rheumatoid arthritis, before and after 6 months' treatment either with penicillamine or with anti-inflammatory drugs. The index was calculated by dividing the sum of the count rates over both knees and both wrists by the dose of technetium given. In the penicillamine group there was a significant reduction in the technetium index and the changes correlated well with some clinical measurements of improvement. It is suggested that the technetium index is a useful objective measure of the effects of drugs with a specific activity in rheumatoid arthritis."} {"id": "PMID:1275587", "title": "Evaluation of dominant thyroid masses.", "content": "Controversy exists concerning the management of solitary thryoid nodules because of conflicting information converning the high clinical incidence of thyroid nodules, the varying incidence of cancer reported in those surgically excised and the infrequency of death from thyroid cancer. During the past several years, a plan for evaluating patients with dominant thyroid masses has evolved. The objective is to avoid unnecessary operations by identifying patients with a high risk of cancer. The criteria which are used are the age and sex of the patient, the duration of the mass, 125I or 99mTc scans, 75Selenomethionine scans, B-mode ultrasonography and the response of the mass to suppressive therapy. This is a report of the findings in 222 patients who have been studied employing this approach. Thirty per cent of the patients were operated upon. Forty per cent had neoplasms (well differentiated cancer--28.8%, adenoma--12.1%), 47.0%--nodular goiter, 6.1% cysts, and 6.1% chronic thyroiditis. The incidence of cancer in the 222 patients was 8.6% and adenoma 3.6%. Patients at greatest risk of having cancer are those with solid nonfunctioning nodules which fail to regress with suppressive therapy. This study indicates that the approach described above is effective in selecting for surgical excision those individuals at greatest risk of having thyroid cancer.", "contents": "Evaluation of dominant thyroid masses. Controversy exists concerning the management of solitary thryoid nodules because of conflicting information converning the high clinical incidence of thyroid nodules, the varying incidence of cancer reported in those surgically excised and the infrequency of death from thyroid cancer. During the past several years, a plan for evaluating patients with dominant thyroid masses has evolved. The objective is to avoid unnecessary operations by identifying patients with a high risk of cancer. The criteria which are used are the age and sex of the patient, the duration of the mass, 125I or 99mTc scans, 75Selenomethionine scans, B-mode ultrasonography and the response of the mass to suppressive therapy. This is a report of the findings in 222 patients who have been studied employing this approach. Thirty per cent of the patients were operated upon. Forty per cent had neoplasms (well differentiated cancer--28.8%, adenoma--12.1%), 47.0%--nodular goiter, 6.1% cysts, and 6.1% chronic thyroiditis. The incidence of cancer in the 222 patients was 8.6% and adenoma 3.6%. Patients at greatest risk of having cancer are those with solid nonfunctioning nodules which fail to regress with suppressive therapy. This study indicates that the approach described above is effective in selecting for surgical excision those individuals at greatest risk of having thyroid cancer."} {"id": "PMID:1275588", "title": "Myxoma of the heart: clinical and experimental observations.", "content": "During the past 12 years, 13 patients with atrial (10 left and 3 right) myxoma have been treated. The tumors of the left atrium produced signs and symptoms of mitral valve obstruction and/or subacute bacterial endocarditis and those of the right atrium manifestations of tricuspid valve disease or of pulmonary embolus or hypertension. The diagnosis was established by angiocardiography in 8 patients, at surgery performed for suspected mitral stenosis in 3 patients, and at autopsy in 2 patients. Resection of the atrial myxoma alone in 5 patients or with atrial septum where the atrial myxoma was attached in 4 or with the whole right atrial wall where the atrial myxoma was attached in one patient was performed and all are doing well without evidence of recurrence. Studies of experimentally produced 1.5-3 cm in diameter left atrial thrombus in 30 dogs divided into 5 groups and followed cineangiocardiographically and sacrificed from 14 days to 6 months indicated that the implanted thrombus is absorbed over a 3 to 6 month period. These experimental and human left atrial thrombi were found to be histologically and histochemically different from human atrial myxomas. The electron microscopic studies performed on some of the resected atrial myxomas suggested that the atrial myxoma cells are active cells of endotheilial origin. These observations suggest that atrial myxoma is a primary tumor of the heart which can mimic other clinical entities, and the results of its surgical treatment are gratifying and long lasting.", "contents": "Myxoma of the heart: clinical and experimental observations. During the past 12 years, 13 patients with atrial (10 left and 3 right) myxoma have been treated. The tumors of the left atrium produced signs and symptoms of mitral valve obstruction and/or subacute bacterial endocarditis and those of the right atrium manifestations of tricuspid valve disease or of pulmonary embolus or hypertension. The diagnosis was established by angiocardiography in 8 patients, at surgery performed for suspected mitral stenosis in 3 patients, and at autopsy in 2 patients. Resection of the atrial myxoma alone in 5 patients or with atrial septum where the atrial myxoma was attached in 4 or with the whole right atrial wall where the atrial myxoma was attached in one patient was performed and all are doing well without evidence of recurrence. Studies of experimentally produced 1.5-3 cm in diameter left atrial thrombus in 30 dogs divided into 5 groups and followed cineangiocardiographically and sacrificed from 14 days to 6 months indicated that the implanted thrombus is absorbed over a 3 to 6 month period. These experimental and human left atrial thrombi were found to be histologically and histochemically different from human atrial myxomas. The electron microscopic studies performed on some of the resected atrial myxomas suggested that the atrial myxoma cells are active cells of endotheilial origin. These observations suggest that atrial myxoma is a primary tumor of the heart which can mimic other clinical entities, and the results of its surgical treatment are gratifying and long lasting."} {"id": "PMID:1275589", "title": "Sphincteroplasty and choledochoduodenostomy for benign biliary obstructions.", "content": "Both sphincteroplasty and choledochoduodenostomy are valuable for choledocholithiasis, stenosis of the terminal bile duct, and occasional cases of pancreatitis. Selection of patients, technical details, and advantages and limitations of both operative procedures are presented. In a personal series of 600 benign biliary operations 73 patients had a sphincteroplasty or choledochoduodenostomy. Sixty of these had a sphincteroplasty without operative mortality, serious complication, or recurrence of biliary problems although 5 still have pain. A positive morphine-prostigmine test was a prime indication for surgery in these 5 patients. The evocative tests are now negative. Thirteen patients had a choledochonduodenostomy without mortality or significant complication. Twelve are symptom free but one has a \"sump syndrome.\" Sphincteroplasty has been preferred because it gives dependent drainage, direct inspection of the ampullary area, and facilitates removal of impacted stones and debris. It is not always applicable and choledochoduodenostomy has been chosen in elderly poor risk patients or in those with pancreatic inflammation or periampullary duodenal diverticula. Both operations have specific advantages and limitations such that the surgeon should not use one to the exclusion of the other.", "contents": "Sphincteroplasty and choledochoduodenostomy for benign biliary obstructions. Both sphincteroplasty and choledochoduodenostomy are valuable for choledocholithiasis, stenosis of the terminal bile duct, and occasional cases of pancreatitis. Selection of patients, technical details, and advantages and limitations of both operative procedures are presented. In a personal series of 600 benign biliary operations 73 patients had a sphincteroplasty or choledochoduodenostomy. Sixty of these had a sphincteroplasty without operative mortality, serious complication, or recurrence of biliary problems although 5 still have pain. A positive morphine-prostigmine test was a prime indication for surgery in these 5 patients. The evocative tests are now negative. Thirteen patients had a choledochonduodenostomy without mortality or significant complication. Twelve are symptom free but one has a \"sump syndrome.\" Sphincteroplasty has been preferred because it gives dependent drainage, direct inspection of the ampullary area, and facilitates removal of impacted stones and debris. It is not always applicable and choledochoduodenostomy has been chosen in elderly poor risk patients or in those with pancreatic inflammation or periampullary duodenal diverticula. Both operations have specific advantages and limitations such that the surgeon should not use one to the exclusion of the other."} {"id": "PMID:1275590", "title": "Long term transhepatic intubation for hilar hepatic duct strictures.", "content": "A technique for repairing benign hilar hepatic duct strictures using transhepatic intubation with a large bore silastic stent is described. This procedure has been used in 10 patients. In 9 instances the stricture involved the common hepatic duct, and in one patient the right and left hepatic ducts. Nine of the strictures followed cholecystectomy; one followed the primary repair of a gun shot wound to the hepatic duct. Hepaticojejunostomies were created and the transhepatic silastic stent was left in place for 6 months in one patient, and for 12 months in 8 patients. In one patient the silastic stents are still in place. There have been no treatment failures. All patients are healthy and at full activity from one year, 3 months to 6 years, 6 months from the time of repair (average 3 years, 5 months). In the 9 patients whose stents have been removed, the serum bilirubin levels are normal There have been no episodes of cholangitis following repair. This method of repair using long term transhepatic silastic stents is recommended for all high hilar hepatic duct strictures.", "contents": "Long term transhepatic intubation for hilar hepatic duct strictures. A technique for repairing benign hilar hepatic duct strictures using transhepatic intubation with a large bore silastic stent is described. This procedure has been used in 10 patients. In 9 instances the stricture involved the common hepatic duct, and in one patient the right and left hepatic ducts. Nine of the strictures followed cholecystectomy; one followed the primary repair of a gun shot wound to the hepatic duct. Hepaticojejunostomies were created and the transhepatic silastic stent was left in place for 6 months in one patient, and for 12 months in 8 patients. In one patient the silastic stents are still in place. There have been no treatment failures. All patients are healthy and at full activity from one year, 3 months to 6 years, 6 months from the time of repair (average 3 years, 5 months). In the 9 patients whose stents have been removed, the serum bilirubin levels are normal There have been no episodes of cholangitis following repair. This method of repair using long term transhepatic silastic stents is recommended for all high hilar hepatic duct strictures."} {"id": "PMID:1275591", "title": "The fate of esophageal varices following selective distal splenorenal shunt.", "content": "Esophagographic evaluation of the fate of esophageal varices after distal splenorenal shunt was obtained. The radiologist-observer was blinded as to the surgical status of the films under study. The results indicate that varices are likely to persist after surgery. However, the sizes of the varices are clearly diminished following selective distal splenorenal shunt. The incidence of postoperative bleeding has been low, 3.7% (2/54) or one episode for each 441 months of postoperative survival.", "contents": "The fate of esophageal varices following selective distal splenorenal shunt. Esophagographic evaluation of the fate of esophageal varices after distal splenorenal shunt was obtained. The radiologist-observer was blinded as to the surgical status of the films under study. The results indicate that varices are likely to persist after surgery. However, the sizes of the varices are clearly diminished following selective distal splenorenal shunt. The incidence of postoperative bleeding has been low, 3.7% (2/54) or one episode for each 441 months of postoperative survival."} {"id": "PMID:1275592", "title": "Unified approach to carcinoma of the esophagus.", "content": "The reversed gastric tube is advocated as a technique to be used in all patients who have carcinomas of the esophagus, whether the lesion is located in the upper, middle or lower esophagus. The tube, constructed out of the greater curvature of the stomach and supplied by the gastroepiploic vessels, invariably has adequate length and sufficient blood supply to heal per primum or to close anastomotic leaks spontaneously when they occur. Since the procedure requires a celiotomy and an incision in the neck, the presence and extent of metastatic disease below the diaphragm and above the clavicle can be evaluated. With prompt resumption of eating, the patients' nutritional status rapidly improves so that they can maintain weight during postoperative irradiation or further surgical procedures, e.g. esophagectomy. It is also effective as a palliative procedure since the patients handle their saliva and other secretions adequately after the procedure.", "contents": "Unified approach to carcinoma of the esophagus. The reversed gastric tube is advocated as a technique to be used in all patients who have carcinomas of the esophagus, whether the lesion is located in the upper, middle or lower esophagus. The tube, constructed out of the greater curvature of the stomach and supplied by the gastroepiploic vessels, invariably has adequate length and sufficient blood supply to heal per primum or to close anastomotic leaks spontaneously when they occur. Since the procedure requires a celiotomy and an incision in the neck, the presence and extent of metastatic disease below the diaphragm and above the clavicle can be evaluated. With prompt resumption of eating, the patients' nutritional status rapidly improves so that they can maintain weight during postoperative irradiation or further surgical procedures, e.g. esophagectomy. It is also effective as a palliative procedure since the patients handle their saliva and other secretions adequately after the procedure."} {"id": "PMID:1275593", "title": "Malignant melanoma in the American Black.", "content": "Malignant melanoma in the American Black is an uncommon disease. Scattered reports have appeared in the literature indicating a somewhat different behavior and distribution from melanoma in the White patient. The last published report prior to the organization of the Tumor Registry at Charity Hospital of Louisiana on melanoma in the Black was in 1948 by Muelling when 28 cases were reported. From 1948 through 1974, 96 additional patients have been recorded in the Charity Hospital Registry which represents the largest reported experience in the American Literature. The average age at diagnosis is 57.8 years as opposed to 53 years for White patients observed over the same time period. The ratio by sex is essentially equal in Blacks. The disease usually presents on the palmar or plantar surfaces of the hands or feet in the Black. In the registry data 51% occurred on the lower limb, 11% on the upper limb, 6% on the trunk, 6% on the genitalia, 1% on the head or neck, 13% were of extradermal origin, and 10% had unknown primary sites. The 5-year cumulative survival for all Black patients in this series is 27%. In contrast to the poor overall survival, a 78% 5-year survival has been achieved in Stage I patients treated with perfusion, wide excision, and regional lymph node dissection.", "contents": "Malignant melanoma in the American Black. Malignant melanoma in the American Black is an uncommon disease. Scattered reports have appeared in the literature indicating a somewhat different behavior and distribution from melanoma in the White patient. The last published report prior to the organization of the Tumor Registry at Charity Hospital of Louisiana on melanoma in the Black was in 1948 by Muelling when 28 cases were reported. From 1948 through 1974, 96 additional patients have been recorded in the Charity Hospital Registry which represents the largest reported experience in the American Literature. The average age at diagnosis is 57.8 years as opposed to 53 years for White patients observed over the same time period. The ratio by sex is essentially equal in Blacks. The disease usually presents on the palmar or plantar surfaces of the hands or feet in the Black. In the registry data 51% occurred on the lower limb, 11% on the upper limb, 6% on the trunk, 6% on the genitalia, 1% on the head or neck, 13% were of extradermal origin, and 10% had unknown primary sites. The 5-year cumulative survival for all Black patients in this series is 27%. In contrast to the poor overall survival, a 78% 5-year survival has been achieved in Stage I patients treated with perfusion, wide excision, and regional lymph node dissection."} {"id": "PMID:1275594", "title": "The surgical treatment of carcinoma of the colon and rectum: an index of quality care and sociologic and geographic distribution.", "content": "A comparative experience of 474 patients with primary carcinoma of the colon and rectum has been evaluated in several hospital settings, with particular respect to patient populations, geographic distribution, and surgical characteristics. The differences and similarities are interpreted with caution but may provide a format by which significant objective determinants become the basis for subsequent assessment of quality care in an illness which is prevalent and amenable to relatively standardized operative management. No difference in quality of medical care provided was detectable across the sociologic and geographic boundaries studied. Notable increases in extent of neoplasm and severity of co-existent illness in the urban, \"indigent\" population adversely influenced both short and long-term mortality rates.", "contents": "The surgical treatment of carcinoma of the colon and rectum: an index of quality care and sociologic and geographic distribution. A comparative experience of 474 patients with primary carcinoma of the colon and rectum has been evaluated in several hospital settings, with particular respect to patient populations, geographic distribution, and surgical characteristics. The differences and similarities are interpreted with caution but may provide a format by which significant objective determinants become the basis for subsequent assessment of quality care in an illness which is prevalent and amenable to relatively standardized operative management. No difference in quality of medical care provided was detectable across the sociologic and geographic boundaries studied. Notable increases in extent of neoplasm and severity of co-existent illness in the urban, \"indigent\" population adversely influenced both short and long-term mortality rates."} {"id": "PMID:1275595", "title": "The curative treatment of carcinoma of the sigmoid, rectosigmoid, and rectum.", "content": "This retrospective series comprises 902 patients who underwent curative resection of the sigmoid colon, rectosigmoid, and upper rectum at the Mayo Clinic during the years 1959 to 1969. Lesions were divided according to the location from the dentate line, with 346 patients having had a lesion located more than 20 cm from the dentate line; in the remaining 556 patients, the lesion was between 6 and 20 cm distant. A thorough analysis was undertaken comparing these two groups of patients on the basis of operative mortality and morbidity, including anastomotic complications, 5- and 10-year survival, and incidence of local recurrence. Overall operative mortality was 1.9%, with an 8.1% incidence of anastomotic complications. The overall 5-year survival rate was 72% and the 10-year survival rate was 55%. The incidence of anastomotic recurrence for anastomosis performed with the use of extraperitoneal rectum was 5.8%; recurrence at the suture line developed in 2.9% of patients who underwent anastomosis to serosa-covered bowel. In addition to the above data, information will be presented which demonstrates the effect of the patient's height and weight on the surgeon's ability to perform a low-anterior anastomosis. Finally, the incidence of anastomotic complications and of local recurrence were analyzed according to the intestinal preparation employed, the use of parenteral antibiotics , and the method of drainage used near the anastomosis.", "contents": "The curative treatment of carcinoma of the sigmoid, rectosigmoid, and rectum. This retrospective series comprises 902 patients who underwent curative resection of the sigmoid colon, rectosigmoid, and upper rectum at the Mayo Clinic during the years 1959 to 1969. Lesions were divided according to the location from the dentate line, with 346 patients having had a lesion located more than 20 cm from the dentate line; in the remaining 556 patients, the lesion was between 6 and 20 cm distant. A thorough analysis was undertaken comparing these two groups of patients on the basis of operative mortality and morbidity, including anastomotic complications, 5- and 10-year survival, and incidence of local recurrence. Overall operative mortality was 1.9%, with an 8.1% incidence of anastomotic complications. The overall 5-year survival rate was 72% and the 10-year survival rate was 55%. The incidence of anastomotic recurrence for anastomosis performed with the use of extraperitoneal rectum was 5.8%; recurrence at the suture line developed in 2.9% of patients who underwent anastomosis to serosa-covered bowel. In addition to the above data, information will be presented which demonstrates the effect of the patient's height and weight on the surgeon's ability to perform a low-anterior anastomosis. Finally, the incidence of anastomotic complications and of local recurrence were analyzed according to the intestinal preparation employed, the use of parenteral antibiotics , and the method of drainage used near the anastomosis."} {"id": "PMID:1275596", "title": "Long-term ventilatory support by diaphragm pacing in quadriplegia.", "content": "Thirty-seven quadriplegic patients with respiratory paralysis were treated by electrical stimulation of the phrenic nerves to pace the diaphragm. Full-time ventilatory support by diaphragm pacing was accomplished in 13 patients. At least half-time support was achieved in 10 others. There were two deaths unrelated to pacing in these two groups. Fourteen patients could not be paced satisfactorily, and 8 of these patients died, most of them from respiratory infections. The average time the 13 patients on total ventilatory support have had bilateral diaphragm pacemakers is 26 months. The longest is 60 months. Many of these patients are out of the hospital and several are in school or working. Injury to the phrenic nerves either by the initial trauma to the cervical cord or during operation for implantation of the nerve cuff was the most significant complication. Nerve damage from prolonged electrical stimulation has not been a problem thus far. A description of the pacemaker, the technique of its implantation, and the pacing schedule are reported.", "contents": "Long-term ventilatory support by diaphragm pacing in quadriplegia. Thirty-seven quadriplegic patients with respiratory paralysis were treated by electrical stimulation of the phrenic nerves to pace the diaphragm. Full-time ventilatory support by diaphragm pacing was accomplished in 13 patients. At least half-time support was achieved in 10 others. There were two deaths unrelated to pacing in these two groups. Fourteen patients could not be paced satisfactorily, and 8 of these patients died, most of them from respiratory infections. The average time the 13 patients on total ventilatory support have had bilateral diaphragm pacemakers is 26 months. The longest is 60 months. Many of these patients are out of the hospital and several are in school or working. Injury to the phrenic nerves either by the initial trauma to the cervical cord or during operation for implantation of the nerve cuff was the most significant complication. Nerve damage from prolonged electrical stimulation has not been a problem thus far. A description of the pacemaker, the technique of its implantation, and the pacing schedule are reported."} {"id": "PMID:1275597", "title": "Pheochromocytoma: present diagnosis and management.", "content": "In the 25-year period 1950-1975 forty-four patients with pheochromocytoma were observed at Vanderbilt University Affiliated Hospitals. Bilateral adrenal tumors occurred in 3 patients (6.8%) and extra-adrenal tumors occurred in 7 others (16%), 33 patients (75%) had single tumors arising in one of the adrenal glands; in one of these 5 years after operation, a malignant tumor developed in the same renal fossa. Five of the 44 patients (11.3%) proved to have malignant tumors and died with metastases. In 11 patients in the earlier years of this study the clinical diagnosis was not made and the tumor was identified by the pathologist at autopsy. There was a single postoperative fatality among the 33 patients in whom the clinical diagnosis was made. Seventy per cent of all survivors with benign tumors have remained normotensive during followup periods of one to 20 years.", "contents": "Pheochromocytoma: present diagnosis and management. In the 25-year period 1950-1975 forty-four patients with pheochromocytoma were observed at Vanderbilt University Affiliated Hospitals. Bilateral adrenal tumors occurred in 3 patients (6.8%) and extra-adrenal tumors occurred in 7 others (16%), 33 patients (75%) had single tumors arising in one of the adrenal glands; in one of these 5 years after operation, a malignant tumor developed in the same renal fossa. Five of the 44 patients (11.3%) proved to have malignant tumors and died with metastases. In 11 patients in the earlier years of this study the clinical diagnosis was not made and the tumor was identified by the pathologist at autopsy. There was a single postoperative fatality among the 33 patients in whom the clinical diagnosis was made. Seventy per cent of all survivors with benign tumors have remained normotensive during followup periods of one to 20 years."} {"id": "PMID:1275598", "title": "Predicted survival in peptic ulcer patients based on computer analysis of preoperative variables.", "content": "A prospective study designed to emphasize and quantitate the operative risk of patients preparing to undergo surgery for the treatment of complicated peptic ulcer disease is presented. Data were gathered from 347 consecutive patients operated on with benign gastric and/or duodenal ulcers in a Veterans Hospital over an 8-year period. Resident surgeons performed all operations and for the most part decided on the operative procedure used, with advice from attending faculty. Preoperative factors influencing the operative mortality in 34 patients were compared with those in surviving patients and subjected to a multivariant discriminant function analysis by computer. Ten variables were identified as being significantly different (P less than 0.05-P less than 0.01) between the survivor and non-survivor groups. Using the discriminant weights of these variables, a computer program was written to calculate the 30-day operative mortality of any preoperative patient based on this past experience. The accuracy of the program is excellent in good risk patients; i.e., a predicted greater than 90% chance of survival was correct 98.9% of the time with 3 deaths in 279 patients. Patients at the low end of the scale (less than 10%) were predicted with 85% accuracy. In the last 8 months, 29 patients have undergone surgery after prospective computer assessment of their operativ risk. All have survived with a predicted chance of greater than 50%. Four patients died with survival chances predicted at 4, 2, 1, and 1%. The computer may be used as an educational vehicle for sharpening our preoperative assessment of a patient with ulcer disease, particularly regarding operative risk.", "contents": "Predicted survival in peptic ulcer patients based on computer analysis of preoperative variables. A prospective study designed to emphasize and quantitate the operative risk of patients preparing to undergo surgery for the treatment of complicated peptic ulcer disease is presented. Data were gathered from 347 consecutive patients operated on with benign gastric and/or duodenal ulcers in a Veterans Hospital over an 8-year period. Resident surgeons performed all operations and for the most part decided on the operative procedure used, with advice from attending faculty. Preoperative factors influencing the operative mortality in 34 patients were compared with those in surviving patients and subjected to a multivariant discriminant function analysis by computer. Ten variables were identified as being significantly different (P less than 0.05-P less than 0.01) between the survivor and non-survivor groups. Using the discriminant weights of these variables, a computer program was written to calculate the 30-day operative mortality of any preoperative patient based on this past experience. The accuracy of the program is excellent in good risk patients; i.e., a predicted greater than 90% chance of survival was correct 98.9% of the time with 3 deaths in 279 patients. Patients at the low end of the scale (less than 10%) were predicted with 85% accuracy. In the last 8 months, 29 patients have undergone surgery after prospective computer assessment of their operativ risk. All have survived with a predicted chance of greater than 50%. Four patients died with survival chances predicted at 4, 2, 1, and 1%. The computer may be used as an educational vehicle for sharpening our preoperative assessment of a patient with ulcer disease, particularly regarding operative risk."} {"id": "PMID:1275599", "title": "The effects on gastrin and gastric secretion of five current operations for duodenal ulcer.", "content": "We have measured serum gastrin and gastric acid secretion in 66 duodenal ulcer patients before and after vagotomy and pyloroplasty (V + P--15 patients), selective proximal vagotomy without drainage (SPV - D--11 patients), and with drainage (SPV + D--19 patients), and vagotomy, antrectomy, and either gastroduodenostomy (V + BI--15 patients) or gastrojejunostomy (V + BII--6 patients). Basal and peak postprandial gastrin levels were increased in postoperative V + P, SPV - D, and SPV + D patients. Basal and peak postprandial levels of gastrin were unchanged after V + BII, indicative of duodenal release of gastrin. Gastrin response to food was abolished in V + BII patients. Acid output was reliably reduced after all five operations; reduction was greatest in patients after antrectomy and least in patients after SPV. No beneficial results were found with drainage in SPV patients. Acid secretion increased with time in SPV patients, especially those with drainage.", "contents": "The effects on gastrin and gastric secretion of five current operations for duodenal ulcer. We have measured serum gastrin and gastric acid secretion in 66 duodenal ulcer patients before and after vagotomy and pyloroplasty (V + P--15 patients), selective proximal vagotomy without drainage (SPV - D--11 patients), and with drainage (SPV + D--19 patients), and vagotomy, antrectomy, and either gastroduodenostomy (V + BI--15 patients) or gastrojejunostomy (V + BII--6 patients). Basal and peak postprandial gastrin levels were increased in postoperative V + P, SPV - D, and SPV + D patients. Basal and peak postprandial levels of gastrin were unchanged after V + BII, indicative of duodenal release of gastrin. Gastrin response to food was abolished in V + BII patients. Acid output was reliably reduced after all five operations; reduction was greatest in patients after antrectomy and least in patients after SPV. No beneficial results were found with drainage in SPV patients. Acid secretion increased with time in SPV patients, especially those with drainage."} {"id": "PMID:1275600", "title": "Late clinical problems with Beall model 103 and 104 mitral valve prostheses: hemolysis and valve wear.", "content": "The purpose of this study was to determine the influence on hemolysis of the spatial orientation of the struts in the Beall mitral valve prosthesis, Models 103 and 104. Thirteen pairs of patients were selected to match struts oriented parallel and perpendicular to the left ventricular outflow tract axis. The average time after operation was 3.73 years. Complete blood counts and relative serum chemistry values were determined.", "contents": "Late clinical problems with Beall model 103 and 104 mitral valve prostheses: hemolysis and valve wear. The purpose of this study was to determine the influence on hemolysis of the spatial orientation of the struts in the Beall mitral valve prosthesis, Models 103 and 104. Thirteen pairs of patients were selected to match struts oriented parallel and perpendicular to the left ventricular outflow tract axis. The average time after operation was 3.73 years. Complete blood counts and relative serum chemistry values were determined."} {"id": "PMID:1275601", "title": "Successful closure of ventricular septal defect through a left-sided ventriculotomy in corrected transposition of the great vessels.", "content": "Corrected transposition of the great vessels is often associated with other cardiac anomalies. Ventricular septal defect (VSD) is the most common among them. Closure of a VSD is usually performed through a right-sided ventriculotomy. We had previously closed the VSD through the right-sided ventricle in 2 patients with corrected transposition of the great vessels and in 2 others with double-outlet right ventricle with ventricular inversion, which resulted in complete heart block. Recently we have closed the VSD through the left-sided ventricle in 3 patients with corrected transposition, and no block resulted.", "contents": "Successful closure of ventricular septal defect through a left-sided ventriculotomy in corrected transposition of the great vessels. Corrected transposition of the great vessels is often associated with other cardiac anomalies. Ventricular septal defect (VSD) is the most common among them. Closure of a VSD is usually performed through a right-sided ventriculotomy. We had previously closed the VSD through the right-sided ventricle in 2 patients with corrected transposition of the great vessels and in 2 others with double-outlet right ventricle with ventricular inversion, which resulted in complete heart block. Recently we have closed the VSD through the left-sided ventricle in 3 patients with corrected transposition, and no block resulted."} {"id": "PMID:1275602", "title": "Operative repair for tricuspid atresia.", "content": "Twelve patients with tricuspid atresia underwent physiological operative repair. The criteria for their selection for operation included normal pulmonary vascular resistance and normal left atrial and left ventricular end-diastolic pressures. Four patients died (30% mortality). The 8 surviving patients developed pleural effusion, ascites, and hepatomegaly, which markedly improved in the subsequent weeks. Five of the 8 survivors underwent cardiac catheterization. The arterial oxygen saturation in these patients averaged 82% preoperatively, 89% immediately postoperatively, and 94% or better six months later. All had improved subjectively and developed increased exercise tolerance.", "contents": "Operative repair for tricuspid atresia. Twelve patients with tricuspid atresia underwent physiological operative repair. The criteria for their selection for operation included normal pulmonary vascular resistance and normal left atrial and left ventricular end-diastolic pressures. Four patients died (30% mortality). The 8 surviving patients developed pleural effusion, ascites, and hepatomegaly, which markedly improved in the subsequent weeks. Five of the 8 survivors underwent cardiac catheterization. The arterial oxygen saturation in these patients averaged 82% preoperatively, 89% immediately postoperatively, and 94% or better six months later. All had improved subjectively and developed increased exercise tolerance."} {"id": "PMID:1275603", "title": "Atherosclerosis of the internal mammary artery.", "content": "To better evaluate the incidence of atherosclerosis in the internal mammary artery (IMA), 215 IMA segments from routine postmortem examinations were evaluated microscopically. Significant atherosclerotic narrowing was seen in 9 patients (4.2%). No patient had more than a 50% reduction in lumen diameter. The degree of incipient atherosclerosis correlated well with age, hypertension, diabetes, and peripheral vascular disease.", "contents": "Atherosclerosis of the internal mammary artery. To better evaluate the incidence of atherosclerosis in the internal mammary artery (IMA), 215 IMA segments from routine postmortem examinations were evaluated microscopically. Significant atherosclerotic narrowing was seen in 9 patients (4.2%). No patient had more than a 50% reduction in lumen diameter. The degree of incipient atherosclerosis correlated well with age, hypertension, diabetes, and peripheral vascular disease."} {"id": "PMID:1275604", "title": "Direct diagnostic thoracoscopy.", "content": "Direct diagnostic thoracoscopy under general anesthesia using the mediastinoscope or bronchoscope has been done in 40 patients. No deaths or serious morbidity occurred. We recommend the use of this technique when other efforts fail to establish a diagnosis in patients with pleural disease.", "contents": "Direct diagnostic thoracoscopy. Direct diagnostic thoracoscopy under general anesthesia using the mediastinoscope or bronchoscope has been done in 40 patients. No deaths or serious morbidity occurred. We recommend the use of this technique when other efforts fail to establish a diagnosis in patients with pleural disease."} {"id": "PMID:1275605", "title": "Pulmonary giant cell carcinoma.", "content": "Pulmonary giant cell carcinoma is one of the most highly malignant neoplasms of the lung. Eighteen patients with this tumor are presented. Histologically the neoplasm is composed of a preponderance of multinucleated giant cells, round cells, and spindle cells. Some of the most differentiated tumors show adenocarcinomatous foci and ultrastructural features of secretory epithelium favoring its classification as a variant of pulmonary adenocarcinoma. The giant cells of this neoplasm can be differentiated from those encountered in undifferentiated large cell carcinoma and epidermoid carcinoma by the abundant cytoplasm, the presence of more nuclei and nucleoli, and the significant degree of phagocytosis. The clinical picture and roentgenographic findings present no pathognomonic features.", "contents": "Pulmonary giant cell carcinoma. Pulmonary giant cell carcinoma is one of the most highly malignant neoplasms of the lung. Eighteen patients with this tumor are presented. Histologically the neoplasm is composed of a preponderance of multinucleated giant cells, round cells, and spindle cells. Some of the most differentiated tumors show adenocarcinomatous foci and ultrastructural features of secretory epithelium favoring its classification as a variant of pulmonary adenocarcinoma. The giant cells of this neoplasm can be differentiated from those encountered in undifferentiated large cell carcinoma and epidermoid carcinoma by the abundant cytoplasm, the presence of more nuclei and nucleoli, and the significant degree of phagocytosis. The clinical picture and roentgenographic findings present no pathognomonic features."} {"id": "PMID:1275606", "title": "Direct monitoring of arterial pressure in the newborn and infant: a difficult procedure made easy.", "content": "Accurate continuous measurement of arterial blood pressure, especially during and following operation, is indispensable for optimal management of the seriously ill newborn or infant. Conventional indirect techniques (flush technique, auscultation, Doppler monitoring device) for assessing the circulatory status in this age group are not reliable, and a direct method would be preferable. Arterial cannulation in such patients has been discouraged by the technical problems related to former techniques.", "contents": "Direct monitoring of arterial pressure in the newborn and infant: a difficult procedure made easy. Accurate continuous measurement of arterial blood pressure, especially during and following operation, is indispensable for optimal management of the seriously ill newborn or infant. Conventional indirect techniques (flush technique, auscultation, Doppler monitoring device) for assessing the circulatory status in this age group are not reliable, and a direct method would be preferable. Arterial cannulation in such patients has been discouraged by the technical problems related to former techniques."} {"id": "PMID:1275608", "title": "Removal of intraaortic balloon without vascular complications.", "content": "A technique for inserting and removing the intraaortic balloon pump without vascular complications is descirbed. Prevention of clot formation at the graft-arterial junction, preservation of collateral circulation by insertion in the common femoral artery, removal of potentially infected graft material, and enlargement of the common femoral artery by patch angioplasty are important factors.", "contents": "Removal of intraaortic balloon without vascular complications. A technique for inserting and removing the intraaortic balloon pump without vascular complications is descirbed. Prevention of clot formation at the graft-arterial junction, preservation of collateral circulation by insertion in the common femoral artery, removal of potentially infected graft material, and enlargement of the common femoral artery by patch angioplasty are important factors."} {"id": "PMID:1275609", "title": "Transaortic cannulation for balloon pumping: report of a patient undergoing closed chest decannulation.", "content": "A technique is described for introduction of an intraaortic balloon (for circulatory augmentation) through the transverse aorta using a crimped Dacron arterial graft brought out through a lateral skin incision. When balloon pumping is discontinued, the balloon catheter is withdrawn through the percutaneous graft without reopening the chest. The graft is amputated and buried without ill effect.", "contents": "Transaortic cannulation for balloon pumping: report of a patient undergoing closed chest decannulation. A technique is described for introduction of an intraaortic balloon (for circulatory augmentation) through the transverse aorta using a crimped Dacron arterial graft brought out through a lateral skin incision. When balloon pumping is discontinued, the balloon catheter is withdrawn through the percutaneous graft without reopening the chest. The graft is amputated and buried without ill effect."} {"id": "PMID:1275614", "title": "Effects of diphenylhydantoin on cardiac arrhythmias induced by carotid occlusion in the cat.", "content": "The effects of diphenylhydantoin (DPH) on cardiac arrhythmias induced by occlusion of the common carotid arteries were studied in vagotomized cats under light chloralose anesthesia. It was found that the mean effective dose of DPH via the i.v. route was 11.0 mg/kg. When DPH was injected into the vertebral artery, the carotid artery or the 4th cerebral ventricle, the mean effective dose was 0.8, 1.2 and 0.32 mg/kg, respectively, When DPH was injected directly into the posterior hypothalamic regions, the mean effective dose was even smaller, i.e., 0.14 mg/kg. On the other hand, when DPH was injected into the left ventricle of the heart, the mean effective dose was 1.7 mg/kg and the dose was significantly increased to 4.4 mg/kg when cerebral circulation was temporarily occluded. The data suggest that DPH exerts a potent antiarrhythmic effect through its action on the central nervous system. For the cardiac arrhythmias induced by occlusion of the common carotid arteries, it appears likely that DPH acts on the posterior hypothalamus.", "contents": "Effects of diphenylhydantoin on cardiac arrhythmias induced by carotid occlusion in the cat. The effects of diphenylhydantoin (DPH) on cardiac arrhythmias induced by occlusion of the common carotid arteries were studied in vagotomized cats under light chloralose anesthesia. It was found that the mean effective dose of DPH via the i.v. route was 11.0 mg/kg. When DPH was injected into the vertebral artery, the carotid artery or the 4th cerebral ventricle, the mean effective dose was 0.8, 1.2 and 0.32 mg/kg, respectively, When DPH was injected directly into the posterior hypothalamic regions, the mean effective dose was even smaller, i.e., 0.14 mg/kg. On the other hand, when DPH was injected into the left ventricle of the heart, the mean effective dose was 1.7 mg/kg and the dose was significantly increased to 4.4 mg/kg when cerebral circulation was temporarily occluded. The data suggest that DPH exerts a potent antiarrhythmic effect through its action on the central nervous system. For the cardiac arrhythmias induced by occlusion of the common carotid arteries, it appears likely that DPH acts on the posterior hypothalamus."} {"id": "PMID:1275615", "title": "Effects of some dopamine analogs and haloperidol on response to stimulation of adrenergic nerves using cat atria in vitro.", "content": "Dopamine analogs, N, N-dimethyldopamine, apomorphine and 5,6-dihydroxy-2-dimethylaminotetralin (M-7) produced inhibition of positive chronotropic and inotropic responses to transmural stimulation of isolated right atria of cats. Haloperidol antagonized inhibitory effects of dopamine analogs. Also haloperidol increased atrial responses during transmural stimulation. N,N-dimethyldopamine, M-7 and apomorphine did not alter responses to exogenous norepinephrine. Haloperidol did not antagonize the inhibitory effect of clonidine.", "contents": "Effects of some dopamine analogs and haloperidol on response to stimulation of adrenergic nerves using cat atria in vitro. Dopamine analogs, N, N-dimethyldopamine, apomorphine and 5,6-dihydroxy-2-dimethylaminotetralin (M-7) produced inhibition of positive chronotropic and inotropic responses to transmural stimulation of isolated right atria of cats. Haloperidol antagonized inhibitory effects of dopamine analogs. Also haloperidol increased atrial responses during transmural stimulation. N,N-dimethyldopamine, M-7 and apomorphine did not alter responses to exogenous norepinephrine. Haloperidol did not antagonize the inhibitory effect of clonidine."} {"id": "PMID:1275616", "title": "Direct renal effects of sodium acetate in the dog.", "content": "Sodium acetate (AC) is used in clinical medicine as it provides a ready source of fixed base. The direct renal dynamics of this buffer salt are not well known. In anesthetized dogs the left renal artery was infused with solutions of AC. In concentrations of 0.1 to 0.5 muEq/min, the acetate ion was always immediately detected in the urine. There were no demonstrable renal changes in volume, PAH clearance, creatinine clearance or electrolytes during the perfusion periods. Direct infusion of AC into the renal artery did not cause any change in blood pressure. We conclude that AC in the conditions of our experiments did not cause renal vasodilation or changes in renal excretions patterns and appears to have a zero renal threshold.", "contents": "Direct renal effects of sodium acetate in the dog. Sodium acetate (AC) is used in clinical medicine as it provides a ready source of fixed base. The direct renal dynamics of this buffer salt are not well known. In anesthetized dogs the left renal artery was infused with solutions of AC. In concentrations of 0.1 to 0.5 muEq/min, the acetate ion was always immediately detected in the urine. There were no demonstrable renal changes in volume, PAH clearance, creatinine clearance or electrolytes during the perfusion periods. Direct infusion of AC into the renal artery did not cause any change in blood pressure. We conclude that AC in the conditions of our experiments did not cause renal vasodilation or changes in renal excretions patterns and appears to have a zero renal threshold."} {"id": "PMID:1275617", "title": "Hyperaemic responses in two vascular beds of the anaesthetised cat.", "content": "In the chloralosed cat reactive hyperaemia to vessel occlusion, and vascular escape associated with vasoconstriction produced by drugs, have been examined in the hindquarters and splanchnic region, and following periaterial mesenteric nerve stimulation in the splanchnic region. The hyperaemic responses were not of a purinergic nature or mediated by an acetylcholine, histamine, dopamine or beta-adrenoceptor stimulant-like substance, and were independent of adrenergic innervation. These responses may respresent a local mechanism by which the vasculature produces vasodilation in response to reduced blood flow.", "contents": "Hyperaemic responses in two vascular beds of the anaesthetised cat. In the chloralosed cat reactive hyperaemia to vessel occlusion, and vascular escape associated with vasoconstriction produced by drugs, have been examined in the hindquarters and splanchnic region, and following periaterial mesenteric nerve stimulation in the splanchnic region. The hyperaemic responses were not of a purinergic nature or mediated by an acetylcholine, histamine, dopamine or beta-adrenoceptor stimulant-like substance, and were independent of adrenergic innervation. These responses may respresent a local mechanism by which the vasculature produces vasodilation in response to reduced blood flow."} {"id": "PMID:1275618", "title": "Drugs and PGO waves in the lateral geniculate body of the curarized cat. II. PGO wave activity and brain 5-hydroxytryptamine.", "content": "Ponto-geniculo-occipital (PCO) waves induced either by the benzoquinolizine derivative, Ro 4-1284 (=PGO(CPA), were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in the preceding communication. The effect of various drugs interacting with central 5-hydroxytryptaminergic mechanisms on the density (number hr(-1) or number 0.5 hr(-1) of PGO waves was investigated. The density of PGO waves was dose-dependently decreased and the waves were eventually abolished by the precursors of 5-hydroxytryptamine (5-HT), L-tryptophan and 5-hydroxytryptophan. 5-HT itself, injected intracerebroventricularly, tended to diminish the density. Lysergic acid diethylamide (LSD) was an extremely potent depressor of PGO(1284) and PGO(PCPA); psilocybine was almost as potent as LSD, whereas higher doses of N,N-dimethyltryptamine, bufotenine and yohimbine were required for the reduction of PGO waves. A number of tricyclic antidepressants reduced the density of PGO waves, their order of potency corresponding to that reported for their inhibitory effect on the uptake of 5-HT; tertiary amines were more potent than secondary amines. Desipramine was more potent on PGO(PCPA) THAN ON PGO(1284). Two dibenzothiepine antipsychotics, methiothepin and octoclothepin, increased the density of PGO(1284) and PGO(PCPA) and also induced PGO waves in untreated cats; the evidence suggests that these two compounds antagonize the effect of endogenous 5-HT in the brain. These results confirm some earlier findings and augment the pharmacological pieces of evidence for the stron inhibitory influence of 5-HT neurones on the generation ofPGO waves.", "contents": "Drugs and PGO waves in the lateral geniculate body of the curarized cat. II. PGO wave activity and brain 5-hydroxytryptamine. Ponto-geniculo-occipital (PCO) waves induced either by the benzoquinolizine derivative, Ro 4-1284 (=PGO(CPA), were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in the preceding communication. The effect of various drugs interacting with central 5-hydroxytryptaminergic mechanisms on the density (number hr(-1) or number 0.5 hr(-1) of PGO waves was investigated. The density of PGO waves was dose-dependently decreased and the waves were eventually abolished by the precursors of 5-hydroxytryptamine (5-HT), L-tryptophan and 5-hydroxytryptophan. 5-HT itself, injected intracerebroventricularly, tended to diminish the density. Lysergic acid diethylamide (LSD) was an extremely potent depressor of PGO(1284) and PGO(PCPA); psilocybine was almost as potent as LSD, whereas higher doses of N,N-dimethyltryptamine, bufotenine and yohimbine were required for the reduction of PGO waves. A number of tricyclic antidepressants reduced the density of PGO waves, their order of potency corresponding to that reported for their inhibitory effect on the uptake of 5-HT; tertiary amines were more potent than secondary amines. Desipramine was more potent on PGO(PCPA) THAN ON PGO(1284). Two dibenzothiepine antipsychotics, methiothepin and octoclothepin, increased the density of PGO(1284) and PGO(PCPA) and also induced PGO waves in untreated cats; the evidence suggests that these two compounds antagonize the effect of endogenous 5-HT in the brain. These results confirm some earlier findings and augment the pharmacological pieces of evidence for the stron inhibitory influence of 5-HT neurones on the generation ofPGO waves."} {"id": "PMID:1275619", "title": "Drugs and PGO waves in the lateral geniculate body of the curarized cat. III. PGO wave activity and brain catecholamines.", "content": "The possible implication of central catecholamines in the phasic phenomenon of ponto-geniculo-occipital (PGO) waves was investigated using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 (=PGO(1284), and the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (=PGO(PCPA); they were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in a previous report. The effect on PGO(1284) and PGO(PCPA) of various drugs interacting with the different steps of catecholaminergic transmission was studie. Injections of noradrenaline (NA) and of dopamine (DA) into the lateral brain ventricle tended to decrease the density of PGO(1284). The stimulant of central alpha-adrenoceptors, clonidine, suppressed PGO(1284) and PGO(PCPA) in very small doses. Apomorphine in high doses had inconsistent depressant effects which were probably not related to its stimulant action on DA receptors. Release of brain NA by dexamphetamine and beta-tetrahydronaphthylamine decreased the density of PGO waves, alpha-Methyldopa diminished PGO(PCPA) but not PGO(1284. The MAO-inhibitor, nialamide, depressed PGO(PCPA) more than PCO(1284), whereas pheniprazine was inactive. The inhibitor of catechol-O-methyltransferase, tropolone, reduced the density of bially blocks the uptake of NA, was more potent on PGO(PCPA) than on PGO(1284). The alpha-adrenoceptor blocking agent, phenosybenzamine, markedly increased the density of PGO(PCPA). Similar effects were obtained with thioridazine and clozapine, which aare also known to be blockers of central alpha-adrenoceptors. Inhibition of tyrosine hydroxylase (by alpha-methyltyrosine) and of DA-beta-hydroxylase (by disulfiram or Ro 8-1981), in addition to the inhibition of tryptophan hydroxylase by PCPA, induced PGO waves comparable in density and temporal distribution to those occurring following the application of Ro 4-1284. The acute bilateral lesion of the dorsal and caudal parts of thel ocus coeruleus increased the density of PGO(PCPA). The results strongly suggest that, in addition to the 5-hydroxytryptaminergic system, noradrenergic neurones, probably originating in the locus coeruleus, depress the neurones in the pontine reticular formation involved in the generation of PGO waves.", "contents": "Drugs and PGO waves in the lateral geniculate body of the curarized cat. III. PGO wave activity and brain catecholamines. The possible implication of central catecholamines in the phasic phenomenon of ponto-geniculo-occipital (PGO) waves was investigated using PGO waves induced by the benzoquinolizine derivative, Ro 4-1284 (=PGO(1284), and the inhibitor of tryptophan hydroxylase, p-chlorophenylalanine (=PGO(PCPA); they were continuously recorded and counted in the lateral geniculate bodies of unanaesthetized immobilized cats as described in a previous report. The effect on PGO(1284) and PGO(PCPA) of various drugs interacting with the different steps of catecholaminergic transmission was studie. Injections of noradrenaline (NA) and of dopamine (DA) into the lateral brain ventricle tended to decrease the density of PGO(1284). The stimulant of central alpha-adrenoceptors, clonidine, suppressed PGO(1284) and PGO(PCPA) in very small doses. Apomorphine in high doses had inconsistent depressant effects which were probably not related to its stimulant action on DA receptors. Release of brain NA by dexamphetamine and beta-tetrahydronaphthylamine decreased the density of PGO waves, alpha-Methyldopa diminished PGO(PCPA) but not PGO(1284. The MAO-inhibitor, nialamide, depressed PGO(PCPA) more than PCO(1284), whereas pheniprazine was inactive. The inhibitor of catechol-O-methyltransferase, tropolone, reduced the density of bially blocks the uptake of NA, was more potent on PGO(PCPA) than on PGO(1284). The alpha-adrenoceptor blocking agent, phenosybenzamine, markedly increased the density of PGO(PCPA). Similar effects were obtained with thioridazine and clozapine, which aare also known to be blockers of central alpha-adrenoceptors. Inhibition of tyrosine hydroxylase (by alpha-methyltyrosine) and of DA-beta-hydroxylase (by disulfiram or Ro 8-1981), in addition to the inhibition of tryptophan hydroxylase by PCPA, induced PGO waves comparable in density and temporal distribution to those occurring following the application of Ro 4-1284. The acute bilateral lesion of the dorsal and caudal parts of thel ocus coeruleus increased the density of PGO(PCPA). The results strongly suggest that, in addition to the 5-hydroxytryptaminergic system, noradrenergic neurones, probably originating in the locus coeruleus, depress the neurones in the pontine reticular formation involved in the generation of PGO waves."} {"id": "PMID:1275620", "title": "Triamterene-induced changes in aldosterone and renin values in essential hypertension. Evidence of a role for aldosterone in preventing blood pressure reduction.", "content": "The effect of triamterene, a potassium-retaining natriuretic and diuretic agent, on arterial blood pressure was studied in 31 patients with essential hypertension; there were seven patients with low plasma renin activity and 24 patients with normal plasma renin activity. Triamterene exhibited mild antihypertensive action, somewhat more pronounced in the low-renin group. The patients were also analyzed by considering them in terms of their blood pressure response. Of the 21 patients in the nonresponder group, no blood pressure decrease occurred, despite induced volume depletion accompanied by an increased plasma renin activity and a concomitant rise in the aldosterone excretion. In contrast, the ten patients in the responder group exhibited a fall in blood pressure, but the aldosterone excretion rate did not change significantly, even though plasma renin activity increased significantly. Moreover, only in the nonresponder group did the stimulated aldosterone excretion rate correlate significantly with the stimulated plasma renin activity. Thus, the failure of triamterene to lower blood pressure in the nonresponder group can be closely related to a significant increase in aldosterone excretion rate. The data suggest the operation of a reactive pressor action mediated by aldosterone, independent of its sodium-retaining effect.", "contents": "Triamterene-induced changes in aldosterone and renin values in essential hypertension. Evidence of a role for aldosterone in preventing blood pressure reduction. The effect of triamterene, a potassium-retaining natriuretic and diuretic agent, on arterial blood pressure was studied in 31 patients with essential hypertension; there were seven patients with low plasma renin activity and 24 patients with normal plasma renin activity. Triamterene exhibited mild antihypertensive action, somewhat more pronounced in the low-renin group. The patients were also analyzed by considering them in terms of their blood pressure response. Of the 21 patients in the nonresponder group, no blood pressure decrease occurred, despite induced volume depletion accompanied by an increased plasma renin activity and a concomitant rise in the aldosterone excretion. In contrast, the ten patients in the responder group exhibited a fall in blood pressure, but the aldosterone excretion rate did not change significantly, even though plasma renin activity increased significantly. Moreover, only in the nonresponder group did the stimulated aldosterone excretion rate correlate significantly with the stimulated plasma renin activity. Thus, the failure of triamterene to lower blood pressure in the nonresponder group can be closely related to a significant increase in aldosterone excretion rate. The data suggest the operation of a reactive pressor action mediated by aldosterone, independent of its sodium-retaining effect."} {"id": "PMID:1275621", "title": "Delay in the prehospital phase of acute myocardial infarction. Lack of influence on incidence of sudden death.", "content": "Prehospital delay is considered to be an important cause of out-of-hospital coronary mortality. Behavior of patients and physicians in response to the symptoms of myocardial infarction (MI) or impending out-of-hospital death (OHD) was studied for 107 consecutive acute coronary events in Framingham, Mass. Delay due to inappropriate patient behavior was the most important component of total delay. Delay related to patient-physician contact occurred in two thirds of MI cases and was more than 30 minutes in half of these. Office visits and inappropriate triage by nurses and receptionists were important factors in physician delay. However, 60% to 75% of OHDs occur so rapidly that their prevention by reduction of prehospital delay seems impossible. A strategy for reduction of delay that might be of benefit in preventing some of the remaining OHDs is described.", "contents": "Delay in the prehospital phase of acute myocardial infarction. Lack of influence on incidence of sudden death. Prehospital delay is considered to be an important cause of out-of-hospital coronary mortality. Behavior of patients and physicians in response to the symptoms of myocardial infarction (MI) or impending out-of-hospital death (OHD) was studied for 107 consecutive acute coronary events in Framingham, Mass. Delay due to inappropriate patient behavior was the most important component of total delay. Delay related to patient-physician contact occurred in two thirds of MI cases and was more than 30 minutes in half of these. Office visits and inappropriate triage by nurses and receptionists were important factors in physician delay. However, 60% to 75% of OHDs occur so rapidly that their prevention by reduction of prehospital delay seems impossible. A strategy for reduction of delay that might be of benefit in preventing some of the remaining OHDs is described."} {"id": "PMID:1275622", "title": "Endoscopy - related bacteremia. Incidence of positive blood cultures after endoscopy of upper gastrointestinal tract.", "content": "A prospective study was undertaken to determine the frequency of bacteremia after endoscopy of the upper gastrointestinal tract. Three of 100 patients (3%) demonstrated positive blood cultures after the endoscopic procedure. Bacteriologic surveys disclosed that routine cleansing procedures of the endoscopy room and the endoscope itself frequently failed to achieve optimal sterile conditions. Particularly noteworthy was the growth of Enterobacter liquefaciens and Candida albicans on one occasion from the endoscope tip. We conclude that, although the incidence of postendoscopy positive blood cultures is low, a more vigorous approach to using clean equipment in clean surroundings is needed when dealing with a potentially susceptible host.", "contents": "Endoscopy - related bacteremia. Incidence of positive blood cultures after endoscopy of upper gastrointestinal tract. A prospective study was undertaken to determine the frequency of bacteremia after endoscopy of the upper gastrointestinal tract. Three of 100 patients (3%) demonstrated positive blood cultures after the endoscopic procedure. Bacteriologic surveys disclosed that routine cleansing procedures of the endoscopy room and the endoscope itself frequently failed to achieve optimal sterile conditions. Particularly noteworthy was the growth of Enterobacter liquefaciens and Candida albicans on one occasion from the endoscope tip. We conclude that, although the incidence of postendoscopy positive blood cultures is low, a more vigorous approach to using clean equipment in clean surroundings is needed when dealing with a potentially susceptible host."} {"id": "PMID:1275623", "title": "Aminocaproic acid in prolonged hematuria of patients with sicklemia.", "content": "Forty-four episodes of sicklemic hematuria occurring in 40 patients during a 12-year period were reviewed. Seven of seven patients had evidence of a hyperactive fibrinolytic system. Fifteen of 38 pyelograms demonstrated obstruction of some portion of the collecting system by blood clots that cleared on follow-up studies (nine patients) in 2 to 37 days. Hematuria subsided spontaneously in 20 episodes. Aminocaproic acid was used in 22 patients whose hematuria prior to aminocaproic acid administration averaged twice as long as the total duration in patients undergoint spontaneous remission. Hematuria subsided in 2.2 +/- 0.3 days in the group treated with aminocaproic acid. Therapy with aminocaproic acid in this study was not associated with an increased incidence of thrombosis. Because of its potential untoward effects, however, EACA therapy in this disorder should be limited to patients with severe or prolonged hematuria.", "contents": "Aminocaproic acid in prolonged hematuria of patients with sicklemia. Forty-four episodes of sicklemic hematuria occurring in 40 patients during a 12-year period were reviewed. Seven of seven patients had evidence of a hyperactive fibrinolytic system. Fifteen of 38 pyelograms demonstrated obstruction of some portion of the collecting system by blood clots that cleared on follow-up studies (nine patients) in 2 to 37 days. Hematuria subsided spontaneously in 20 episodes. Aminocaproic acid was used in 22 patients whose hematuria prior to aminocaproic acid administration averaged twice as long as the total duration in patients undergoint spontaneous remission. Hematuria subsided in 2.2 +/- 0.3 days in the group treated with aminocaproic acid. Therapy with aminocaproic acid in this study was not associated with an increased incidence of thrombosis. Because of its potential untoward effects, however, EACA therapy in this disorder should be limited to patients with severe or prolonged hematuria."} {"id": "PMID:1275624", "title": "Lymphocyte blastogenesis in patients receiving hemodialysis.", "content": "Lymphocyte blastogenic transformation in response to plant lectins and allogenic cells was studied in patients with nonuremic, far-advanced, chronic renal failure and in healthy controls. Cell cultures were studied in the presence of normal sera, patient's sera, and with media of different buffering capacities. Minimal blastogenic depression was observed when patient's lymphocytes were cultured in indifferent plasma with effective bicarbonate buffering compared with the use of pooled patient's plasma or HEPES buffer. Fresh plasma in culture depressed concanavalin A (Con A) blastogenesis. The data suggest that, under optimal conditions, lymphocytes from patients with chronic severe renal insufficiency are more responsive to stimuli than previously reported and as a group are near normal control values. Further, the defect observed may be a result of intracellular acidosis.", "contents": "Lymphocyte blastogenesis in patients receiving hemodialysis. Lymphocyte blastogenic transformation in response to plant lectins and allogenic cells was studied in patients with nonuremic, far-advanced, chronic renal failure and in healthy controls. Cell cultures were studied in the presence of normal sera, patient's sera, and with media of different buffering capacities. Minimal blastogenic depression was observed when patient's lymphocytes were cultured in indifferent plasma with effective bicarbonate buffering compared with the use of pooled patient's plasma or HEPES buffer. Fresh plasma in culture depressed concanavalin A (Con A) blastogenesis. The data suggest that, under optimal conditions, lymphocytes from patients with chronic severe renal insufficiency are more responsive to stimuli than previously reported and as a group are near normal control values. Further, the defect observed may be a result of intracellular acidosis."} {"id": "PMID:1275625", "title": "Hypocalcemia after therapeutic use of magnesium sulfate.", "content": "It is now recognized that magnesium plays an important role in calcium homeostasis. Although the effects of hypomagnesemia have been frequently reported, little has been written to suggest a clinically important role for hypermagnesemia. A case is reported in which severe hypocalcemia, with a low plasma parathyroid hormone (PTH) concentration, resulted from the therapeutic use of magnesium sulfate for toxemia of pregnancy. Following recovery, the parathyroid glands were shown to respond normally to a phosphate load. It is suggested that the hypermagnesemia directly suppressed PTH secretion, resulting in symptomatic hypocalcemia.", "contents": "Hypocalcemia after therapeutic use of magnesium sulfate. It is now recognized that magnesium plays an important role in calcium homeostasis. Although the effects of hypomagnesemia have been frequently reported, little has been written to suggest a clinically important role for hypermagnesemia. A case is reported in which severe hypocalcemia, with a low plasma parathyroid hormone (PTH) concentration, resulted from the therapeutic use of magnesium sulfate for toxemia of pregnancy. Following recovery, the parathyroid glands were shown to respond normally to a phosphate load. It is suggested that the hypermagnesemia directly suppressed PTH secretion, resulting in symptomatic hypocalcemia."} {"id": "PMID:1275626", "title": "Incidence of acute exertional rhabdomyolysis. Serum myoglobin and enzyme levels as indicators of muscle injury.", "content": "This study was conducted to determine, on a prospective basis, the incidence of acute exertional rhabdomyolysis (AER) among recruits at the Marine Corps Recruit Depot, San Diego, Calif. Blood samples were taken from each of 337 volunteer recruits on each of their first six days of regularly scheduled training. Serum myoglobin, serum creatine phosphokinase, lactic dehydrogenase, and serum glutamic oxaloacetic transaminase values were used as indicators of muscle injury. Substantial elevations of serum enzyme activity were observed throughout the study population. Of the study population, 39.2% had serum myoglobin levels that ranged from 0.37 mug/ml to 21.9 mug/ml during the study interval. Six subjects had serum myoglobin levels consistent with those reported in clinical cases of AER. It is concluded that, in a recruit population, large numbers of men may have myoglobinemia but not be seen initially as clinical cases.", "contents": "Incidence of acute exertional rhabdomyolysis. Serum myoglobin and enzyme levels as indicators of muscle injury. This study was conducted to determine, on a prospective basis, the incidence of acute exertional rhabdomyolysis (AER) among recruits at the Marine Corps Recruit Depot, San Diego, Calif. Blood samples were taken from each of 337 volunteer recruits on each of their first six days of regularly scheduled training. Serum myoglobin, serum creatine phosphokinase, lactic dehydrogenase, and serum glutamic oxaloacetic transaminase values were used as indicators of muscle injury. Substantial elevations of serum enzyme activity were observed throughout the study population. Of the study population, 39.2% had serum myoglobin levels that ranged from 0.37 mug/ml to 21.9 mug/ml during the study interval. Six subjects had serum myoglobin levels consistent with those reported in clinical cases of AER. It is concluded that, in a recruit population, large numbers of men may have myoglobinemia but not be seen initially as clinical cases."} {"id": "PMID:1275627", "title": "Beh\u00e7et syndrome with \"aphthous colitis\".", "content": "A 46-year-old man with Beh\u00e7et syndrome and a long history of recurrent bouts of colitis was studied by sigmoidoscopy, barium enema x-ray film, and colon biopsy. A nonspecific colitis characterized by shallow mucosal ulcerations and submucosal mononuclear infiltration in the absence of meaningful roentgenolographic changes was seen. A histopathological comparison was made between the oral and colonic lesions. The aphthous colitis appears, therefore, to be a colonic manifestation of Beh\u00e7et syndrome, differing from typical chronic nonspecific ulcerative colitis in terms of clinical course, severity, and histologic appearance. The simultaneous occurrence of Beh\u00e7et syndrome and inflammatory disease of the colon was discussed in terms of the differential diagnosis of colitis.", "contents": "Beh\u00e7et syndrome with \"aphthous colitis\". A 46-year-old man with Beh\u00e7et syndrome and a long history of recurrent bouts of colitis was studied by sigmoidoscopy, barium enema x-ray film, and colon biopsy. A nonspecific colitis characterized by shallow mucosal ulcerations and submucosal mononuclear infiltration in the absence of meaningful roentgenolographic changes was seen. A histopathological comparison was made between the oral and colonic lesions. The aphthous colitis appears, therefore, to be a colonic manifestation of Beh\u00e7et syndrome, differing from typical chronic nonspecific ulcerative colitis in terms of clinical course, severity, and histologic appearance. The simultaneous occurrence of Beh\u00e7et syndrome and inflammatory disease of the colon was discussed in terms of the differential diagnosis of colitis."} {"id": "PMID:1275628", "title": "Derman necrosis due to thrombosis in severe secondary hyperparathyroidism.", "content": "Two patients had gangrenous dermal necrosis associated with chronic renal disease and secondary hyperparathyroidism. Thromobosed and heavily calcified small arteries were underlying the infarcted areas. One patient had severe hypotension secondary to hemorrhage, which immediately preceded the appearance of dermal lesions. Both patients had notably elevated serum parathyroid hormone and serum alkaline phosphatase levels, as well as severe hyperphosphatemia. Therapy with phosphate binders and calcium and vitamin D supplementation corrected the hyperphosphatemia and reduced serum alkaline phosphatase levels. One patient died; the other patient's dermal lesions healed completely. Localized thrombosis, rather than obliterative intimal proliferation, represents a unique cause of dermal necrosis in this condition.", "contents": "Derman necrosis due to thrombosis in severe secondary hyperparathyroidism. Two patients had gangrenous dermal necrosis associated with chronic renal disease and secondary hyperparathyroidism. Thromobosed and heavily calcified small arteries were underlying the infarcted areas. One patient had severe hypotension secondary to hemorrhage, which immediately preceded the appearance of dermal lesions. Both patients had notably elevated serum parathyroid hormone and serum alkaline phosphatase levels, as well as severe hyperphosphatemia. Therapy with phosphate binders and calcium and vitamin D supplementation corrected the hyperphosphatemia and reduced serum alkaline phosphatase levels. One patient died; the other patient's dermal lesions healed completely. Localized thrombosis, rather than obliterative intimal proliferation, represents a unique cause of dermal necrosis in this condition."} {"id": "PMID:1275629", "title": "Cerebral embolization resulting from esophageal-atrial fistula.", "content": "A rare but catastrophic complication of nontraumatic esophageal perforation is the formation of an esophageal-left atrial fistula. Although surgical correction of this condition should be possible, failure to recognize it antemortem has thus far prevented such intervention. A woman with long-standing severe esophagitis, was admitted with hematemesis and acute neurologic abnormalities that progressed to coma and death. A similar picture of chronic esophagitis terminating in uppergastrointestinal-tract bleeding accompanied by neurologic signs was seen in the three previously reported cases as well. Recognition of this symptom complex should permit future cases to be diagnosed clinically, and, it is hoped, corrected.", "contents": "Cerebral embolization resulting from esophageal-atrial fistula. A rare but catastrophic complication of nontraumatic esophageal perforation is the formation of an esophageal-left atrial fistula. Although surgical correction of this condition should be possible, failure to recognize it antemortem has thus far prevented such intervention. A woman with long-standing severe esophagitis, was admitted with hematemesis and acute neurologic abnormalities that progressed to coma and death. A similar picture of chronic esophagitis terminating in uppergastrointestinal-tract bleeding accompanied by neurologic signs was seen in the three previously reported cases as well. Recognition of this symptom complex should permit future cases to be diagnosed clinically, and, it is hoped, corrected."} {"id": "PMID:1275630", "title": "Editorial: The crisis in access.", "content": "During the last 50 years, great changes have occurred in the patterns of medical care in the United States. These changes have seriously affected physician geographic and specialty distribution and have escalated costs. New forces are developing that may have great effects on the actions of the health professions and the content of their educational programs. Orientation will change from cure to that of total health care and prevention. Today's emphasis seems directed toward comprehensive family health care, using the expertise of many new health professionals as members of a joint effort. The patient must become part of this health program by assuming an active role in the health maintenance of the individual and society. Such responsibility can be assumed by the patient only if health professionals provide access to information and knowledge.", "contents": "Editorial: The crisis in access. During the last 50 years, great changes have occurred in the patterns of medical care in the United States. These changes have seriously affected physician geographic and specialty distribution and have escalated costs. New forces are developing that may have great effects on the actions of the health professions and the content of their educational programs. Orientation will change from cure to that of total health care and prevention. Today's emphasis seems directed toward comprehensive family health care, using the expertise of many new health professionals as members of a joint effort. The patient must become part of this health program by assuming an active role in the health maintenance of the individual and society. Such responsibility can be assumed by the patient only if health professionals provide access to information and knowledge."} {"id": "PMID:1275633", "title": "[Determination of folates in food. Comparative and critical study].", "content": "A study on the microbiologic method for folate determination in natural products was carried out. The variables that must be considered were analyzed previous to the application of this technique, that is: nature of combinations of the compounds with vitamin activity, function and distribution of the conjugases, capacity of absorption of the polyglutamates present in foods, natural inhibitors of the conjugases and the importance of the selection of the microorganism used. Based on the preliminary investigations a modified microbiological microtechnique is proposed and its importance for some nutricional aspects is discussed.", "contents": "[Determination of folates in food. Comparative and critical study]. A study on the microbiologic method for folate determination in natural products was carried out. The variables that must be considered were analyzed previous to the application of this technique, that is: nature of combinations of the compounds with vitamin activity, function and distribution of the conjugases, capacity of absorption of the polyglutamates present in foods, natural inhibitors of the conjugases and the importance of the selection of the microorganism used. Based on the preliminary investigations a modified microbiological microtechnique is proposed and its importance for some nutricional aspects is discussed."} {"id": "PMID:1275634", "title": "[Coffee pulp and hulls. XI. Chemical characteristics of silaged coffee pulp with Napier grass (Pennisetum purpurem) and corn plant (Zea mays)].", "content": "Various physical and chemical changes that occur during the process of preparation of coffee pulp silage with the addition of molasses and forage, were identified and measured quantitatively. Three types of silage were prepared in duplicate in laboratory concrete silos, 45 cm wide and 50 cm high. The silages contained the following components: coffee pulp (EPC), pulp and Napier grass (EPCN), and pulp with corn fodder (EPCM). On a fresh basis, the last two contained equal proportions of coffee pulp and forage. Around 16% molasses were aded to all silages. Time of ensiling was 132 to 141 days. In order to determine the physical changes, the silage was weighed at the start and end of the ensiling period; the pH was determined at the end of same, and the drained liquids were measured during the experimental period. To determine the chemical changes, analyses were carried out on the various components used and on the mixtures ensiled at the start and at the end of the experimental period. The pH of the silage was 4.5, 4.3, and 3.8, and the losses of dry matter 10.6, 25.2, and 33.3% for the three types of silages, respectively. These percentages suggest that a better fermentation took place in those silages containing forages. The better fermentation of EPCN over EPC was due to the Napier grass which provided greater amounts of chemical components susceptible of fermentation than those found in coffee pulp. The quality of EPCM was superior due not only to the presence of corn fodder, which produced an effect similar to that of Napier grass, but also due to the fact that the coffee pulp used in this case contained the greater concentrations of soluble carbohydrates and lower levels of lignin than the coffee pulp used alone or with Napier grass. As a result of the fermentation process, in all three types of silage a decrease in dry matter content, of cellular contents and soluble carbohydrates was observed, as well as an increase in cellular walls and its components, and of protein. The magnitude of these changes was found to be directly related to the losses in dry matter. From the results of this research, it was concluded that the addition of forage improves the chemical characteristics of silage prepared from coffee pulp.", "contents": "[Coffee pulp and hulls. XI. Chemical characteristics of silaged coffee pulp with Napier grass (Pennisetum purpurem) and corn plant (Zea mays)]. Various physical and chemical changes that occur during the process of preparation of coffee pulp silage with the addition of molasses and forage, were identified and measured quantitatively. Three types of silage were prepared in duplicate in laboratory concrete silos, 45 cm wide and 50 cm high. The silages contained the following components: coffee pulp (EPC), pulp and Napier grass (EPCN), and pulp with corn fodder (EPCM). On a fresh basis, the last two contained equal proportions of coffee pulp and forage. Around 16% molasses were aded to all silages. Time of ensiling was 132 to 141 days. In order to determine the physical changes, the silage was weighed at the start and end of the ensiling period; the pH was determined at the end of same, and the drained liquids were measured during the experimental period. To determine the chemical changes, analyses were carried out on the various components used and on the mixtures ensiled at the start and at the end of the experimental period. The pH of the silage was 4.5, 4.3, and 3.8, and the losses of dry matter 10.6, 25.2, and 33.3% for the three types of silages, respectively. These percentages suggest that a better fermentation took place in those silages containing forages. The better fermentation of EPCN over EPC was due to the Napier grass which provided greater amounts of chemical components susceptible of fermentation than those found in coffee pulp. The quality of EPCM was superior due not only to the presence of corn fodder, which produced an effect similar to that of Napier grass, but also due to the fact that the coffee pulp used in this case contained the greater concentrations of soluble carbohydrates and lower levels of lignin than the coffee pulp used alone or with Napier grass. As a result of the fermentation process, in all three types of silage a decrease in dry matter content, of cellular contents and soluble carbohydrates was observed, as well as an increase in cellular walls and its components, and of protein. The magnitude of these changes was found to be directly related to the losses in dry matter. From the results of this research, it was concluded that the addition of forage improves the chemical characteristics of silage prepared from coffee pulp."} {"id": "PMID:1275635", "title": "[Socioeconomic level of the family and nutrition in the rural area of Central America and Panama].", "content": "During the nutrition survey carried out in Central America and Panama in 1965-1967, information was obtained on the diets and nutrient intake of the rural populations, and on their anthropometric and nutritional-biochemical characteristics. Simultaneously, data were collected for each family studied, which permitted their categorization according to a scale of socioeconomic index. The findings of these studies demonstrate a direct relationship between the socioeconomic level of the families and their dietary and nutritional characteristics. The different types of data, that is, dietary, biochemical, anthropometric and socioeconomic, were all collected at the same time in order to avoid seasonal differences as a confounding factor. Restriction of the sample studied to the rural area of the six countries makes each population rather homogeneous with respect to environmental, genetic and cultural characteristics. Under these conditions, the direct association found between the socioeconomic index of the families and nutritional status acquires more meaning. The design of the study does not permit to determine the direction of a cause-effect relationship, that is, which is the cause of the other. Nevertheless, the findings lend themselves to interesting speculation in this regard.", "contents": "[Socioeconomic level of the family and nutrition in the rural area of Central America and Panama]. During the nutrition survey carried out in Central America and Panama in 1965-1967, information was obtained on the diets and nutrient intake of the rural populations, and on their anthropometric and nutritional-biochemical characteristics. Simultaneously, data were collected for each family studied, which permitted their categorization according to a scale of socioeconomic index. The findings of these studies demonstrate a direct relationship between the socioeconomic level of the families and their dietary and nutritional characteristics. The different types of data, that is, dietary, biochemical, anthropometric and socioeconomic, were all collected at the same time in order to avoid seasonal differences as a confounding factor. Restriction of the sample studied to the rural area of the six countries makes each population rather homogeneous with respect to environmental, genetic and cultural characteristics. Under these conditions, the direct association found between the socioeconomic index of the families and nutritional status acquires more meaning. The design of the study does not permit to determine the direction of a cause-effect relationship, that is, which is the cause of the other. Nevertheless, the findings lend themselves to interesting speculation in this regard."} {"id": "PMID:1275636", "title": "Malnutrition, kidney size and composition.", "content": "Kidneys from 42 infants were analysed for protein, fat, water, DNA and RNA. No significant differences in composition could be found between groups of children with different degrees of weight deficit. However, in a larger series of 200, it was shown that increasing degrees of weight deficit were associated with a reduction in kidney size. In the older children with the greatest degree of weight deficit, the kidney formed a significantly higher percentage of the body weight. The general conclusion is that in the most severely malnourished children kidneys are smaller than normal.", "contents": "Malnutrition, kidney size and composition. Kidneys from 42 infants were analysed for protein, fat, water, DNA and RNA. No significant differences in composition could be found between groups of children with different degrees of weight deficit. However, in a larger series of 200, it was shown that increasing degrees of weight deficit were associated with a reduction in kidney size. In the older children with the greatest degree of weight deficit, the kidney formed a significantly higher percentage of the body weight. The general conclusion is that in the most severely malnourished children kidneys are smaller than normal."} {"id": "PMID:1275637", "title": "[Composition of bean broth].", "content": "Bean broth is used as weaning food. Six samples were studied as well as the respective residues and the raw beans from which they were obtained. The proportion of components found in the broths expressed as percentage of that in the raw beans was 11.9% for proteins, 9.4% for triptophane, 4.7% for lysine, 5.6% for methionine, 3.2% for cystine, 13.1% for thiamin, 26.5% for riboflavin and 24.1% for niacin. Cooking losses were greatest in cystine, thiamin and niacin. According to these results, the broths proteins have a lower nutritive values than the cooked beans.", "contents": "[Composition of bean broth]. Bean broth is used as weaning food. Six samples were studied as well as the respective residues and the raw beans from which they were obtained. The proportion of components found in the broths expressed as percentage of that in the raw beans was 11.9% for proteins, 9.4% for triptophane, 4.7% for lysine, 5.6% for methionine, 3.2% for cystine, 13.1% for thiamin, 26.5% for riboflavin and 24.1% for niacin. Cooking losses were greatest in cystine, thiamin and niacin. According to these results, the broths proteins have a lower nutritive values than the cooked beans."} {"id": "PMID:1275638", "title": "The end products of the metabolism of aromatic amino acids by Clostridia.", "content": "The end products of the metabolism of phenylalanine, tyrosine and tryptophan by growing cultures of clostridia have been identified. The species used were Clostridium aminovalericum; C. bifermentans; C. botulinum proteolytic type A; C. botulinum proteolytic type B; C. cochlearium; C. difficile; C. ghoni; C. histolyticum; C. lentoputrescens; C. limosum; C. lituseburense; C. malenomenatum; C. mangenoti; C. propionicum; C. putrefaciens; C. sordellii; C. sporogenes; C. sporosphaeroides; C. sticklandii; C. subterminale; C. tetani; C. tetanomorphum. The mixture of aromatic compounds formed, which depended upon the species, included phenyl acetic acid, phenyl propionic acid, phenyl lactic acid, phenol, p-cresol, p-hydroxy phenyl acetic acid, p-hydroxy phenyl propionic acid, indole, indole acetic acid and indole propionic acid.", "contents": "The end products of the metabolism of aromatic amino acids by Clostridia. The end products of the metabolism of phenylalanine, tyrosine and tryptophan by growing cultures of clostridia have been identified. The species used were Clostridium aminovalericum; C. bifermentans; C. botulinum proteolytic type A; C. botulinum proteolytic type B; C. cochlearium; C. difficile; C. ghoni; C. histolyticum; C. lentoputrescens; C. limosum; C. lituseburense; C. malenomenatum; C. mangenoti; C. propionicum; C. putrefaciens; C. sordellii; C. sporogenes; C. sporosphaeroides; C. sticklandii; C. subterminale; C. tetani; C. tetanomorphum. The mixture of aromatic compounds formed, which depended upon the species, included phenyl acetic acid, phenyl propionic acid, phenyl lactic acid, phenol, p-cresol, p-hydroxy phenyl acetic acid, p-hydroxy phenyl propionic acid, indole, indole acetic acid and indole propionic acid."} {"id": "PMID:1275639", "title": "The cryopreservation of Chlorella. 2. Effect of growth temperature on freezing tolerance.", "content": "The temperature at which Chlorella 211/8h was grown determined the response to a subsequent stress of freezing to and thawing from-196 degrees C. Cells cultured at 20 degrees C were the most sensitive to freezing injury; at both higher and lower growth temperatures resistance to damage induced by freezing developed. At all culture temperatures examined the freezing tolerance varied with the age of culture.", "contents": "The cryopreservation of Chlorella. 2. Effect of growth temperature on freezing tolerance. The temperature at which Chlorella 211/8h was grown determined the response to a subsequent stress of freezing to and thawing from-196 degrees C. Cells cultured at 20 degrees C were the most sensitive to freezing injury; at both higher and lower growth temperatures resistance to damage induced by freezing developed. At all culture temperatures examined the freezing tolerance varied with the age of culture."} {"id": "PMID:1275640", "title": "The fine structure of Micrococcus radiophilus and Micrococcus radioproteolyticus.", "content": "The radiation resistant bacteria Micrococcus radiophilus and M. radioproteolyticus were studied by thin sectioning and freez-etching techniques and the two species were found to be similar in the fine structure. The only significant difference was in the appearance of the surfaces of the cell walls in freeze-etched preparations. Since the two species, together with M. radiodurans, possess a unique cell wall structure and a cell wall peptidoglycan, which is different from that of other micrococci and Gram-positive cocci, it is recommended that they be reclassified into a new genus.", "contents": "The fine structure of Micrococcus radiophilus and Micrococcus radioproteolyticus. The radiation resistant bacteria Micrococcus radiophilus and M. radioproteolyticus were studied by thin sectioning and freez-etching techniques and the two species were found to be similar in the fine structure. The only significant difference was in the appearance of the surfaces of the cell walls in freeze-etched preparations. Since the two species, together with M. radiodurans, possess a unique cell wall structure and a cell wall peptidoglycan, which is different from that of other micrococci and Gram-positive cocci, it is recommended that they be reclassified into a new genus."} {"id": "PMID:1275641", "title": "Origin of sclerotia-like cells in submerged Claviceps purpurea producing clavine alkaloids.", "content": "Ultrathin sectioning of submerged mycelium of Claviceps purpurea Tul. producing clavine alkaloids revealed yeast-like budding resulting in asexual spores-blastospores. These deciduous spores were born by extended hyphal cells and retained the same ultrastructure of cell organelles. Both the extended hyphae and the blastospores resembled the cells of ergot sclerotial tissue. A surface culture of C. purpurea Tul. producing no alkaloids was used as a reference.", "contents": "Origin of sclerotia-like cells in submerged Claviceps purpurea producing clavine alkaloids. Ultrathin sectioning of submerged mycelium of Claviceps purpurea Tul. producing clavine alkaloids revealed yeast-like budding resulting in asexual spores-blastospores. These deciduous spores were born by extended hyphal cells and retained the same ultrastructure of cell organelles. Both the extended hyphae and the blastospores resembled the cells of ergot sclerotial tissue. A surface culture of C. purpurea Tul. producing no alkaloids was used as a reference."} {"id": "PMID:1275642", "title": "[On the essential oil of green algae. I. The oils of the genus Chlorella (author's transl)].", "content": "Unicellular green algae of the genus Chlorella are able to synthesize essential oils. Some guajanolides (i.e., proazulenes) were shown to be its main components. Certain species produce as much oil as do higher plants. Formation of essential oils can serve as a taxonomic character in the genus Chlorella.", "contents": "[On the essential oil of green algae. I. The oils of the genus Chlorella (author's transl)]. Unicellular green algae of the genus Chlorella are able to synthesize essential oils. Some guajanolides (i.e., proazulenes) were shown to be its main components. Certain species produce as much oil as do higher plants. Formation of essential oils can serve as a taxonomic character in the genus Chlorella."} {"id": "PMID:1275643", "title": "[The metabolic interactions between Paramecium bursaria Ehrbg. and Chlorella spec. in the Paramecium bursaria-symbiosis. I. The nitrogen and the carbon metabolism (author's transl)].", "content": "Symbiotic Chlorellae have been isolated from Paramecium bursaria Ehrbg. and cultivated under conditions of nitrogen deficiency. Reinfection of Chlorella-free Paramecium bursaria with these nitrogen-deficient algae resulted in a complete regeneration and multiplication of the algae within the host cells. The endosymbiotic algal cells of the Paramecium bursaria-symbiosis can be supplied by their host with nitrogen. The inhibition of photosynthesis by 3-(3,4-Dichlorophenyl)-1,1-dimethylurea (DCMU) leads in green Paramecium bursaria to a breakdown of the symbiotic steady state-system resulting in a loss of algal cells. Obviously the endosymbiotic algae cannot be fed heterotrophically by their host to such an extent that a stable symbiosis is maintained. The application of 3-(3,4-Dichlorophenyl)-1,1-dimethylurea (DCMU) can be used as a new method for culturing Chlorella-free Paramecium bursaria.", "contents": "[The metabolic interactions between Paramecium bursaria Ehrbg. and Chlorella spec. in the Paramecium bursaria-symbiosis. I. The nitrogen and the carbon metabolism (author's transl)]. Symbiotic Chlorellae have been isolated from Paramecium bursaria Ehrbg. and cultivated under conditions of nitrogen deficiency. Reinfection of Chlorella-free Paramecium bursaria with these nitrogen-deficient algae resulted in a complete regeneration and multiplication of the algae within the host cells. The endosymbiotic algal cells of the Paramecium bursaria-symbiosis can be supplied by their host with nitrogen. The inhibition of photosynthesis by 3-(3,4-Dichlorophenyl)-1,1-dimethylurea (DCMU) leads in green Paramecium bursaria to a breakdown of the symbiotic steady state-system resulting in a loss of algal cells. Obviously the endosymbiotic algae cannot be fed heterotrophically by their host to such an extent that a stable symbiosis is maintained. The application of 3-(3,4-Dichlorophenyl)-1,1-dimethylurea (DCMU) can be used as a new method for culturing Chlorella-free Paramecium bursaria."} {"id": "PMID:1275644", "title": "Effect of 5-fluorouracil and cycloheximide on the early development of Phycomyces blakesleeanus spores and the activity of N-acetylglucosamine synthesizing enzymes.", "content": "The development of germinating Phycomyces spores was not inhibited by 5-fluorouracil (1mM) until the emergence of the germination tube. Fluorouracil was incorporated into RNA as efficiently as uracil; it did not inhibit the synthesis of proteins and the increase in respiratory activity during early development. Cycloheximide inhibited development as well as the increase in respiration and protein synthesis. This suggested that protein synthesis or some other cycloheximide dependent process, but no mRNA synthesis, was needed for the first developmental stages. The activity of two enzymes involved in the synthesis of N-acetylglucosamine increased markedly during germination. THis increase was inhibited by both 5-fluorouracil and cycloheximide; this suggested that those enzymes were synthesized on mRNA formed during germination.", "contents": "Effect of 5-fluorouracil and cycloheximide on the early development of Phycomyces blakesleeanus spores and the activity of N-acetylglucosamine synthesizing enzymes. The development of germinating Phycomyces spores was not inhibited by 5-fluorouracil (1mM) until the emergence of the germination tube. Fluorouracil was incorporated into RNA as efficiently as uracil; it did not inhibit the synthesis of proteins and the increase in respiratory activity during early development. Cycloheximide inhibited development as well as the increase in respiration and protein synthesis. This suggested that protein synthesis or some other cycloheximide dependent process, but no mRNA synthesis, was needed for the first developmental stages. The activity of two enzymes involved in the synthesis of N-acetylglucosamine increased markedly during germination. THis increase was inhibited by both 5-fluorouracil and cycloheximide; this suggested that those enzymes were synthesized on mRNA formed during germination."} {"id": "PMID:1275645", "title": "Cytology of Thamnidium elegans Link. II. Distribution and behaviour of nuclei in hyphae, sporangiophores and sporangiospores.", "content": "The resting nuclei in hyphae, sporangiophores and sporangiospores of sporangia and sporangiola of Thamnidium elegans consist of a large centrals nucleolus and a shell of chromatin surrounding the nucleolus. Division of the nucleus in hyphae and sporangiospores is achieved by elongation and constriction.", "contents": "Cytology of Thamnidium elegans Link. II. Distribution and behaviour of nuclei in hyphae, sporangiophores and sporangiospores. The resting nuclei in hyphae, sporangiophores and sporangiospores of sporangia and sporangiola of Thamnidium elegans consist of a large centrals nucleolus and a shell of chromatin surrounding the nucleolus. Division of the nucleus in hyphae and sporangiospores is achieved by elongation and constriction."} {"id": "PMID:1275646", "title": "Identification and physiological characterization of the nitrogen fixing bacterium Corynebacterium autotrophicum GZ 29.", "content": "The coryneform hydrogen bacterium strain GZ 29, assigned to Corynebacterium autotrophicum fixed molecular nitrogen under autotrophic (H2, CO2) as well as under heterotrophic (sucrose) conditions. Physiological parameters of nitrogen fixation were measured under heterotrophic conditions. The optimal dissolved oxygen concentration for cells grown in a fermenter with N2 was rather low (0.14 mg O2/l) compared with cells grown in the presence of NH+4 (4.45 mg O2/l). C. autotrophicum GZ 29 had a doubling time of 3.7 h at 30 degrees C with N2 as N-source and sucrose as carbon source and at optimal pO2. Acetylene reduction reached values of 12 nmoles of ethylene produced/min X mg protein. Although the oxygen concentration in the growing culture was kept constant, the optimal dissolved oxygen tension for the acetylene reduction assay shifted to higher pO2-values. The overall efficiency of nitrogen fixation amounted to 22 mg N fixed/g sucrose consumed; it reached a maximal value of 65 mg N fixed/g sucrose consumed at the beginning of the exponential growth phase. Intact cells reduced acetylene even under anaerobic test conditions; further anaerobic metabolic activity could not be ascertained so far.", "contents": "Identification and physiological characterization of the nitrogen fixing bacterium Corynebacterium autotrophicum GZ 29. The coryneform hydrogen bacterium strain GZ 29, assigned to Corynebacterium autotrophicum fixed molecular nitrogen under autotrophic (H2, CO2) as well as under heterotrophic (sucrose) conditions. Physiological parameters of nitrogen fixation were measured under heterotrophic conditions. The optimal dissolved oxygen concentration for cells grown in a fermenter with N2 was rather low (0.14 mg O2/l) compared with cells grown in the presence of NH+4 (4.45 mg O2/l). C. autotrophicum GZ 29 had a doubling time of 3.7 h at 30 degrees C with N2 as N-source and sucrose as carbon source and at optimal pO2. Acetylene reduction reached values of 12 nmoles of ethylene produced/min X mg protein. Although the oxygen concentration in the growing culture was kept constant, the optimal dissolved oxygen tension for the acetylene reduction assay shifted to higher pO2-values. The overall efficiency of nitrogen fixation amounted to 22 mg N fixed/g sucrose consumed; it reached a maximal value of 65 mg N fixed/g sucrose consumed at the beginning of the exponential growth phase. Intact cells reduced acetylene even under anaerobic test conditions; further anaerobic metabolic activity could not be ascertained so far."} {"id": "PMID:1275647", "title": "Hyphal wall chemistry in Apodachlya.", "content": "Hyphal walls were isolated from the Oomycete, Apodachlya sp. Microscope examination of wall preparations showed that they were clean and relatively free of cellulin granules. The principal wall constituents, accounting for more than half of wall weight, were beta-glucans with 1,3- and 1,6-glucosidic linkages. Apparently chitin was the second most abundant wall constituent (18%) and cellulose accounted for less than 10% of wall weight. Protein was a significant wall constituent (6.4%), and protein hydrolysis demonstrated nearly all common amino acids plus hydroxyproline; additionally, the unusual amino acid, hydroxylysine was tentatively identified. The lipid and ash constituents were small (1.7and 0.4%, respectively) and no particular significance was assigned to them. The possible occurrence of wall glycoproteins and the relationship between wall chemistry and systematics in Apodachlya and related genera were discussed.", "contents": "Hyphal wall chemistry in Apodachlya. Hyphal walls were isolated from the Oomycete, Apodachlya sp. Microscope examination of wall preparations showed that they were clean and relatively free of cellulin granules. The principal wall constituents, accounting for more than half of wall weight, were beta-glucans with 1,3- and 1,6-glucosidic linkages. Apparently chitin was the second most abundant wall constituent (18%) and cellulose accounted for less than 10% of wall weight. Protein was a significant wall constituent (6.4%), and protein hydrolysis demonstrated nearly all common amino acids plus hydroxyproline; additionally, the unusual amino acid, hydroxylysine was tentatively identified. The lipid and ash constituents were small (1.7and 0.4%, respectively) and no particular significance was assigned to them. The possible occurrence of wall glycoproteins and the relationship between wall chemistry and systematics in Apodachlya and related genera were discussed."} {"id": "PMID:1275648", "title": "Hyphal walls of isolated lichen fungi: autoradiographic localization of precursor incorporation and binding of fluorescein-conjugated lectins.", "content": "The hyphal walls of three mycobionts, isolated from the lichens Xanthoria parietina, Tornabenia intricata and Sarcogyne sp. were investigated by two techniques: microautoradiography of fungal colonies exposed to radioactive carbohydrate precursors: and binding, in vivo, of fluorescein conjugated lectins to hyphal walls of such colonies. N-[3H] acetylglucosamine was readily incorporated into tips, young hyphal walls and septa of the three mycobionts and the free-living fungus Trichoderma viride, but not into Phytophthora citrophthora, indicating that chitin is a major component of the mycobionts' hyphal walls. All three mycobionts, but neither of the free-living fungi, incorporated [3H] mannose and [3H] mannitol into their hyphal walls. Fluorescein-conjugated wheat germ agglutinin was bound to the hyphal walls of the three mycobionts and T. viride, but not to the walls of P. citrophthora; the binding pattern was similar to the grain pattern obtained in autoradiographs after short N-[3H]acetylglucosamine labelling. As wheat germ agglutinin binds specifically to chitin oligomers, the lectin binding tests further confirmed that chitin is a mycobiont hyphal wall component. Binding characteristics of several fluorescein-conjugated lectins to the three mycobionts indicated that this technique can yield useful information concerning the chemical composition of hyphal wall surfaces.", "contents": "Hyphal walls of isolated lichen fungi: autoradiographic localization of precursor incorporation and binding of fluorescein-conjugated lectins. The hyphal walls of three mycobionts, isolated from the lichens Xanthoria parietina, Tornabenia intricata and Sarcogyne sp. were investigated by two techniques: microautoradiography of fungal colonies exposed to radioactive carbohydrate precursors: and binding, in vivo, of fluorescein conjugated lectins to hyphal walls of such colonies. N-[3H] acetylglucosamine was readily incorporated into tips, young hyphal walls and septa of the three mycobionts and the free-living fungus Trichoderma viride, but not into Phytophthora citrophthora, indicating that chitin is a major component of the mycobionts' hyphal walls. All three mycobionts, but neither of the free-living fungi, incorporated [3H] mannose and [3H] mannitol into their hyphal walls. Fluorescein-conjugated wheat germ agglutinin was bound to the hyphal walls of the three mycobionts and T. viride, but not to the walls of P. citrophthora; the binding pattern was similar to the grain pattern obtained in autoradiographs after short N-[3H]acetylglucosamine labelling. As wheat germ agglutinin binds specifically to chitin oligomers, the lectin binding tests further confirmed that chitin is a mycobiont hyphal wall component. Binding characteristics of several fluorescein-conjugated lectins to the three mycobionts indicated that this technique can yield useful information concerning the chemical composition of hyphal wall surfaces."} {"id": "PMID:1275649", "title": "Polyphosphate granules in encysted zoospores of Rozella allomycis.", "content": "Methods of ultracytochemistry and of X-ray energy dispersive analysis have been used to demonstrate that the \"gamma-like\" granules in encysted zoospores of the chytrid Rozella allomycis contain polyphosphate. The possibility that cysts contain two classes of polyphosphate granules which differ in structure, in function, and in origin is discussed.", "contents": "Polyphosphate granules in encysted zoospores of Rozella allomycis. Methods of ultracytochemistry and of X-ray energy dispersive analysis have been used to demonstrate that the \"gamma-like\" granules in encysted zoospores of the chytrid Rozella allomycis contain polyphosphate. The possibility that cysts contain two classes of polyphosphate granules which differ in structure, in function, and in origin is discussed."} {"id": "PMID:1275650", "title": "[Formation of bactericidal substances by Cosmarium impressulum (author's transl)].", "content": "1. An already published test method for detecting bactericidal substances in paper chromatograms was further improved. 2. In cultures of Cosmarium impressulum free from bacteria, two bactericidal substances were found in the ether extracts from the algae and two others in the extracts of the culture medium. The are active against some or all bacteria testes (Serratia marcescens, Pseudomonas fluorescens; Aerobacter aerogenes or Bacillus pumilus). 3. If the culture medium of Cosmarium or another desmidiale was inoculated with the test bacteria, a clear bactericidal effect was never observed. 4. Because the activity of the bactericidal substances of Cosmarium is only small and the formation is not constant, it is concluded that the water-soluble bactericidal substances of the alga are not the cause that epiphytic bacteria do not grow normally on Cosmarium.", "contents": "[Formation of bactericidal substances by Cosmarium impressulum (author's transl)]. 1. An already published test method for detecting bactericidal substances in paper chromatograms was further improved. 2. In cultures of Cosmarium impressulum free from bacteria, two bactericidal substances were found in the ether extracts from the algae and two others in the extracts of the culture medium. The are active against some or all bacteria testes (Serratia marcescens, Pseudomonas fluorescens; Aerobacter aerogenes or Bacillus pumilus). 3. If the culture medium of Cosmarium or another desmidiale was inoculated with the test bacteria, a clear bactericidal effect was never observed. 4. Because the activity of the bactericidal substances of Cosmarium is only small and the formation is not constant, it is concluded that the water-soluble bactericidal substances of the alga are not the cause that epiphytic bacteria do not grow normally on Cosmarium."} {"id": "PMID:1275651", "title": "Unusual cell structures in tumor-like formations of Gracilaria (Rhodophyta).", "content": "This paper deals with electron microscopic observations on cultivated plants of the marine red alga Gracilaria verrucosa which developed simple galla; also sea collected material, without galls, had been studied. The galls showed unusual but characteristic cell structured, caterpillar-like bodies, containing rows of fusiform bodies. These were found mostly in the cytoplasm near the plastids, in one case connected with the endoplasmic reticulum, occasionally even inside the nucleus, and are described here, as far as we know, for the first time. It does not seem probably that the caterpillar-like bodies represent mitochondria or bacteria, but the hypothesis that fusiform bodies are related to virus-like structures is discussed. The normal tissues as well as the gall tissue of the laboratory plants contained, besides plastids typical for the red algae, another type of plastids characterized by tubular thylakoids.", "contents": "Unusual cell structures in tumor-like formations of Gracilaria (Rhodophyta). This paper deals with electron microscopic observations on cultivated plants of the marine red alga Gracilaria verrucosa which developed simple galla; also sea collected material, without galls, had been studied. The galls showed unusual but characteristic cell structured, caterpillar-like bodies, containing rows of fusiform bodies. These were found mostly in the cytoplasm near the plastids, in one case connected with the endoplasmic reticulum, occasionally even inside the nucleus, and are described here, as far as we know, for the first time. It does not seem probably that the caterpillar-like bodies represent mitochondria or bacteria, but the hypothesis that fusiform bodies are related to virus-like structures is discussed. The normal tissues as well as the gall tissue of the laboratory plants contained, besides plastids typical for the red algae, another type of plastids characterized by tubular thylakoids."} {"id": "PMID:1275652", "title": "Synchronized cultures of a cell wall-less mutant of Chylamydomonas reinhardii.", "content": "Synchronization and synchronous growth of a cell wall-less mutant of Chlamydomonas reinhardii have been described. The following growth conditions were used: A modified Sueokas' \"high salt minimal medium\", 14:10 h light-dark cycle, growth temperature 30 degrees C, light intensity 12-18 Klux and dilution of the culture at the end of the dark to a constant density of 1.0 . 10(6) cells/ml. The time course of increase and distribution of cell volume, cytopla-smic and nuclear division, release of motile cells after the division period and accumulation of DNA, RNA and protein are reported. These mutant cells did not make any sporangium in which the dividing cells were kept as a unit inside a mother cell wall. However, they usually adhered during the period of division, thus making clumps containing 2, 4 and 8 cells. Several of these cell clumps dissolved releasing either single or couples of 2 and 4 cells. After the end of division the cells became fl", "contents": "Synchronized cultures of a cell wall-less mutant of Chylamydomonas reinhardii. Synchronization and synchronous growth of a cell wall-less mutant of Chlamydomonas reinhardii have been described. The following growth conditions were used: A modified Sueokas' \"high salt minimal medium\", 14:10 h light-dark cycle, growth temperature 30 degrees C, light intensity 12-18 Klux and dilution of the culture at the end of the dark to a constant density of 1.0 . 10(6) cells/ml. The time course of increase and distribution of cell volume, cytopla-smic and nuclear division, release of motile cells after the division period and accumulation of DNA, RNA and protein are reported. These mutant cells did not make any sporangium in which the dividing cells were kept as a unit inside a mother cell wall. However, they usually adhered during the period of division, thus making clumps containing 2, 4 and 8 cells. Several of these cell clumps dissolved releasing either single or couples of 2 and 4 cells. After the end of division the cells became fl"} {"id": "PMID:1275653", "title": "Physical properties and metabolite regulation of ribulose bisphosphate carboxylase from Thiobacillus A2.", "content": "Purified ribulose-bisphosphate carboxylase (EC 4.1.1.39) was strongly and equally inhibited either by ADP or GDP and to a lesser extent by IDP. AMP or ATP exerted little effect on activity. Inhibition by the nucleotide diphosphates was competitive with respect to RuBP and non-competitive with respect to \"CO2\" and Mg2+, respectively. Treatment of the enzyme with urea or guanidine-HCl resulted in rapid loss of activity that was not restored by dialysis even in the presence of Mg2+ and cysteine. Sodium dodecyl sulfate electrophoresis of 8.0 M urea treated enzyme revealed the presence of a fast-moving (small) sub-unit with molecular weight 14150 and a slower moving (large) sub-unit with molecular weight 68000. Examination of native enzyme by sodium dodecyl sulfate electrophoresis gave sub-units of 13700 and 55500 respectively. The amino acid content standardized to phenylalanine was essentially similar to that from other sources. Arrhenius plots showed a \"break\" at 29 degrees C with an Ea of 12.34 kcal per mole for the steeper part of the curve and a deltaH of 11.43 kcal per mole while for the less steep region, the Ea was 1.04 kcal per mole and the deltaH 1.92 kcal per mole.", "contents": "Physical properties and metabolite regulation of ribulose bisphosphate carboxylase from Thiobacillus A2. Purified ribulose-bisphosphate carboxylase (EC 4.1.1.39) was strongly and equally inhibited either by ADP or GDP and to a lesser extent by IDP. AMP or ATP exerted little effect on activity. Inhibition by the nucleotide diphosphates was competitive with respect to RuBP and non-competitive with respect to \"CO2\" and Mg2+, respectively. Treatment of the enzyme with urea or guanidine-HCl resulted in rapid loss of activity that was not restored by dialysis even in the presence of Mg2+ and cysteine. Sodium dodecyl sulfate electrophoresis of 8.0 M urea treated enzyme revealed the presence of a fast-moving (small) sub-unit with molecular weight 14150 and a slower moving (large) sub-unit with molecular weight 68000. Examination of native enzyme by sodium dodecyl sulfate electrophoresis gave sub-units of 13700 and 55500 respectively. The amino acid content standardized to phenylalanine was essentially similar to that from other sources. Arrhenius plots showed a \"break\" at 29 degrees C with an Ea of 12.34 kcal per mole for the steeper part of the curve and a deltaH of 11.43 kcal per mole while for the less steep region, the Ea was 1.04 kcal per mole and the deltaH 1.92 kcal per mole."} {"id": "PMID:1275657", "title": "Light and scanning electron microscopic studies on the esophageal spines in the Pacific ridley turtle, Lepidochelys olivacea.", "content": "The peculairly specialized esophagus of the Pacific ridley turtle, Lepidochelys olivacea, was described by light and scanning electron microscopic studies. The esophagus is lined by a stratified squamous epithelium with remarkable keratinization, and its major part forms a number of large spines which have been called \"pharyngeal teeth.\" The epithelium consists of three strate: stratum germinativum, stratum spinosum and stratum corneum. The surface of the spine is covered by a scaly keratin of possibly sloughing cells, and the cornified layer on the spine is very thick (more than 100 mu), reaching 3 to 7 times the depth of the corresponding layer in other parts. This peculiar structure in the marine turtle without toothed jaws prabably is used for breaking food into small pieces.", "contents": "Light and scanning electron microscopic studies on the esophageal spines in the Pacific ridley turtle, Lepidochelys olivacea. The peculairly specialized esophagus of the Pacific ridley turtle, Lepidochelys olivacea, was described by light and scanning electron microscopic studies. The esophagus is lined by a stratified squamous epithelium with remarkable keratinization, and its major part forms a number of large spines which have been called \"pharyngeal teeth.\" The epithelium consists of three strate: stratum germinativum, stratum spinosum and stratum corneum. The surface of the spine is covered by a scaly keratin of possibly sloughing cells, and the cornified layer on the spine is very thick (more than 100 mu), reaching 3 to 7 times the depth of the corresponding layer in other parts. This peculiar structure in the marine turtle without toothed jaws prabably is used for breaking food into small pieces."} {"id": "PMID:1275658", "title": "Kinetics of protein synthesis and release in the STH-cell of the mouse anterior pituitary as revealed by electron microscopic autoradiography of 3H-amino acids.", "content": "In order to investigate the kinetics of the synthesis and release of the secretory protein in the STH-secreting cell of the pituitary anterior lobe, studies were made using the electron microscopic autoradiography of 3H-amino acids. Each mouse received an intravenous injection of 2.8 mCi of 3H-amino acids consisting of equal amounts of 3H-leucine, 3H-tyrosine, 3H-lysine, 3H-histidine and 3H-glycine. The animal was sacrificed at 3, 5, 15 and 30 min, 1, 2, 4, 8 and 24 hrs after the injection. Although the whole silver grains are very few 3 min after the injection, half of the grains are recognized over the r-ER (47.1%); the Golgi apparatus already shows a few grains (5.9%). Total silver grains over the STH-cell increase in number with the lapse of time; the ratio of the grain number over the r-ER to the total grains over the whole cell decreases gradually, while the ratio of the grain number over the Golgi apparatus increases to reach a peak about 30 min after the injection (40.1%) and then decreases gradually. The ratio of the number of labelled granules to that of total granules increases slowly until 24 hrs after the injection (3 min: 0%, 5 min: 0.8%, 30 min: 3.9%, 2 hrs: 5.0%, 8 hrs: 8.0%, 24 hrs: 12.3%). It is concluded that the turnover in synthesis and release of exportable protein in the mouse STH-cell is very slow as compared with that of the thyroid and parathyroid cell.", "contents": "Kinetics of protein synthesis and release in the STH-cell of the mouse anterior pituitary as revealed by electron microscopic autoradiography of 3H-amino acids. In order to investigate the kinetics of the synthesis and release of the secretory protein in the STH-secreting cell of the pituitary anterior lobe, studies were made using the electron microscopic autoradiography of 3H-amino acids. Each mouse received an intravenous injection of 2.8 mCi of 3H-amino acids consisting of equal amounts of 3H-leucine, 3H-tyrosine, 3H-lysine, 3H-histidine and 3H-glycine. The animal was sacrificed at 3, 5, 15 and 30 min, 1, 2, 4, 8 and 24 hrs after the injection. Although the whole silver grains are very few 3 min after the injection, half of the grains are recognized over the r-ER (47.1%); the Golgi apparatus already shows a few grains (5.9%). Total silver grains over the STH-cell increase in number with the lapse of time; the ratio of the grain number over the r-ER to the total grains over the whole cell decreases gradually, while the ratio of the grain number over the Golgi apparatus increases to reach a peak about 30 min after the injection (40.1%) and then decreases gradually. The ratio of the number of labelled granules to that of total granules increases slowly until 24 hrs after the injection (3 min: 0%, 5 min: 0.8%, 30 min: 3.9%, 2 hrs: 5.0%, 8 hrs: 8.0%, 24 hrs: 12.3%). It is concluded that the turnover in synthesis and release of exportable protein in the mouse STH-cell is very slow as compared with that of the thyroid and parathyroid cell."} {"id": "PMID:1275659", "title": "An electron microscopic study of the olfactory mucosa in the bat and rabbit.", "content": "The olfactory epithelium and the olfactory gland were electron microscopically observed in the bat and rabbit. 1. In spite of abundant tubular components of sER, the supporting cells show no cytological signs of secretory activity. Numerous long irregular microvilli which are protruded from the supporting cells into the mucous film covering the olfactory epithelium contain no axial filaments. From the outer leaflet of the plasma membrane covering these cells and their microvilli, numerous polypoid processes are projected into the mucous film. These newly identified delicate processes with an apical vesicular swelling about 200 A in diameter may be involved in an extension of surface area or in a microapocrine release of unknown substance. 2. Olfactory cell perikaryon extends an apical dendrite forming an olfactory vesicle (better to be called \"dendritic bulb\") and a basal neurite or axon. Basal bodies of olfactory cilia are contained in the dendritic bulb and provided with 3 types of appendages: one or occasionally 2 striated conical basal feet directed toward the center of the dendritic bulb, an occasional 1.2 mu long striated rootlet and 9 spokes which extend between the distal end of each of 9 triplets of the basal body and the surface plasma membrane. 3. The present study has first disclosed the so-called \"large dense-cored vesicles\" about 750-1,000 A in diameter in the perikaryons and axons of olfactory cells. The dendrite and axon contain numerous neurotubules and mitochondria, but no neurofilaments. Cytological differences between dendrite and axon consist in that the former contains scattering free ribosomes but no large dense-cored vesicles, while the latter contains no free ribosomes but some large dense-cored vesicles. 4. Undifferentiated basal cells containing no tonofilaments, which are supposed to differentiate through mitosis into \"intercalated cells,\" are proposed in this paper. Electron-lucent intercalated cells show cytological characteristics of undifferentiated cells, and may probably be precursors of both olfactory and supporting cells. 5. In the bat and rabbit olfactory gland, the presence of an intraepithelial excretory duct surrounded by proper epithelial cells lacking in secretory function seems doubtful. The olfactory gland seems to lack a basement membrane. Secretory cells are in various stages of the secretory cycle, but no distinct cell types have been distinguished. Secretory granules of low density with dense cores support, together with their histochemical properties, the mucous nature of the olfactory gland in both species, though the rich tubular elements of sER may suggest a possible peculiar nature of their secretions. Rabbit secretory cells contain \"dense rodlets,\" which are probably derived from the tubular sER. They are discharged by apocrine process into the glandular lumen.", "contents": "An electron microscopic study of the olfactory mucosa in the bat and rabbit. The olfactory epithelium and the olfactory gland were electron microscopically observed in the bat and rabbit. 1. In spite of abundant tubular components of sER, the supporting cells show no cytological signs of secretory activity. Numerous long irregular microvilli which are protruded from the supporting cells into the mucous film covering the olfactory epithelium contain no axial filaments. From the outer leaflet of the plasma membrane covering these cells and their microvilli, numerous polypoid processes are projected into the mucous film. These newly identified delicate processes with an apical vesicular swelling about 200 A in diameter may be involved in an extension of surface area or in a microapocrine release of unknown substance. 2. Olfactory cell perikaryon extends an apical dendrite forming an olfactory vesicle (better to be called \"dendritic bulb\") and a basal neurite or axon. Basal bodies of olfactory cilia are contained in the dendritic bulb and provided with 3 types of appendages: one or occasionally 2 striated conical basal feet directed toward the center of the dendritic bulb, an occasional 1.2 mu long striated rootlet and 9 spokes which extend between the distal end of each of 9 triplets of the basal body and the surface plasma membrane. 3. The present study has first disclosed the so-called \"large dense-cored vesicles\" about 750-1,000 A in diameter in the perikaryons and axons of olfactory cells. The dendrite and axon contain numerous neurotubules and mitochondria, but no neurofilaments. Cytological differences between dendrite and axon consist in that the former contains scattering free ribosomes but no large dense-cored vesicles, while the latter contains no free ribosomes but some large dense-cored vesicles. 4. Undifferentiated basal cells containing no tonofilaments, which are supposed to differentiate through mitosis into \"intercalated cells,\" are proposed in this paper. Electron-lucent intercalated cells show cytological characteristics of undifferentiated cells, and may probably be precursors of both olfactory and supporting cells. 5. In the bat and rabbit olfactory gland, the presence of an intraepithelial excretory duct surrounded by proper epithelial cells lacking in secretory function seems doubtful. The olfactory gland seems to lack a basement membrane. Secretory cells are in various stages of the secretory cycle, but no distinct cell types have been distinguished. Secretory granules of low density with dense cores support, together with their histochemical properties, the mucous nature of the olfactory gland in both species, though the rich tubular elements of sER may suggest a possible peculiar nature of their secretions. Rabbit secretory cells contain \"dense rodlets,\" which are probably derived from the tubular sER. They are discharged by apocrine process into the glandular lumen."} {"id": "PMID:1275661", "title": "Histologic and histochemical changes in the aorta and myocardium of rats under the influence of atherogenic diet and phosphatidylcholine (EPL).", "content": "The prophylactic and therapeutic action of EPL on arteriosclerotic changes induced with fat-rich diet in the aorta and myocardium of white rats was studied. Histologic and histochemical studies showed that EPL administered prophylactically in doses of 280 mg/kg and 900 mg/kg body weight does not significantly inhibit development of arteriosclerotic lesions if fat-rich diet is continued. A distinct prophylactic action of EPL was first seen at a dosage of 2800 mg/kg. The therapeutic action of EPL on pathologic changes in the blood vessels also depends on dosage. The higher the dosage of EPL, the less pronounced the changes. At a dosage level of 2800 mg/kg, changes are slight and sporadic.", "contents": "Histologic and histochemical changes in the aorta and myocardium of rats under the influence of atherogenic diet and phosphatidylcholine (EPL). The prophylactic and therapeutic action of EPL on arteriosclerotic changes induced with fat-rich diet in the aorta and myocardium of white rats was studied. Histologic and histochemical studies showed that EPL administered prophylactically in doses of 280 mg/kg and 900 mg/kg body weight does not significantly inhibit development of arteriosclerotic lesions if fat-rich diet is continued. A distinct prophylactic action of EPL was first seen at a dosage of 2800 mg/kg. The therapeutic action of EPL on pathologic changes in the blood vessels also depends on dosage. The higher the dosage of EPL, the less pronounced the changes. At a dosage level of 2800 mg/kg, changes are slight and sporadic."} {"id": "PMID:1275662", "title": "A search for antitumor compounds. XI. Biologic studies. Antitumor properties of 19 new 9-aminoacridine and 1-or 3-nitro-9-aminoacridine derivatives.", "content": "Results of studies on the antitumor activity of six 9-aminoacridine derivatives, four 3-nitro-9-aminoacridine derivatives, four 1-nitro-9-aminoacridine derivatives and five N-oxide of 1-nitro-9-aminoacridine derivatives in mice bearing Sa-180 of compound C-709 requires confirmation by further tests with Sa-180. The remaining 15 compounds were inactive. Some other general effects in the mice and some aspects of the structure-activity relationship are discussed.", "contents": "A search for antitumor compounds. XI. Biologic studies. Antitumor properties of 19 new 9-aminoacridine and 1-or 3-nitro-9-aminoacridine derivatives. Results of studies on the antitumor activity of six 9-aminoacridine derivatives, four 3-nitro-9-aminoacridine derivatives, four 1-nitro-9-aminoacridine derivatives and five N-oxide of 1-nitro-9-aminoacridine derivatives in mice bearing Sa-180 of compound C-709 requires confirmation by further tests with Sa-180. The remaining 15 compounds were inactive. Some other general effects in the mice and some aspects of the structure-activity relationship are discussed."} {"id": "PMID:1275663", "title": "Glycogenolysis in the heart and skeletal muscle during stimulation and blocking of cholinergic receptors. I. Action of parasympathicotonic compounds.", "content": "In vitro changes in enzymatic activities during phosphorolytic and hydrolytic glycogenolysis in the working heart and resting skeletal muscle were studied after intravenous injection of parasympathicotonic compounds. Acetylcholine increased phosphorolytic activity in both muscles and at the same time decreased hydrolytic activity. Since administration of selectively parasympathicotonic compounds such as pilocarpine, furmethide and bethanechol did not produce similar effects, the observed action of acetylcholine does not seem to be connected with the muscarinic receptor. Experiments with isolated muscles (cardiac, skeletal) incubated with acetylcholine gave no results indicating a direct action of acetylcholine on the investigated enzymatic processes.", "contents": "Glycogenolysis in the heart and skeletal muscle during stimulation and blocking of cholinergic receptors. I. Action of parasympathicotonic compounds. In vitro changes in enzymatic activities during phosphorolytic and hydrolytic glycogenolysis in the working heart and resting skeletal muscle were studied after intravenous injection of parasympathicotonic compounds. Acetylcholine increased phosphorolytic activity in both muscles and at the same time decreased hydrolytic activity. Since administration of selectively parasympathicotonic compounds such as pilocarpine, furmethide and bethanechol did not produce similar effects, the observed action of acetylcholine does not seem to be connected with the muscarinic receptor. Experiments with isolated muscles (cardiac, skeletal) incubated with acetylcholine gave no results indicating a direct action of acetylcholine on the investigated enzymatic processes."} {"id": "PMID:1275664", "title": "Glycogenolysis in the heart and skeletal muscle during stimulation and blocking of cholinergic receptors. II. Action of cholinolytic compounds.", "content": "In Part I of this study it was found that slow injection of acetylcholine causes an increase in phosphorolytic activity in the working heart and resting skeletal muscle, and at the same time decreases hydrolytic activity. At present, it is shown that atropine and tubocurarine do not inhibit this activity of acetylcholine, but that it is inhibited by blocking the N1 receptor with hexamethonium. These findings indicate that neither the muscarinic receptor in the heart nor the nicotinic N2 receptor in skeletal muscle take part in regulation of glycogenolysis, which is connected with the action of acetylcholine on the cholinergic N1 receptor. Ganglioplegic compounds stimulate hydrolytic activity (hexamethonium, atropine in large doses).", "contents": "Glycogenolysis in the heart and skeletal muscle during stimulation and blocking of cholinergic receptors. II. Action of cholinolytic compounds. In Part I of this study it was found that slow injection of acetylcholine causes an increase in phosphorolytic activity in the working heart and resting skeletal muscle, and at the same time decreases hydrolytic activity. At present, it is shown that atropine and tubocurarine do not inhibit this activity of acetylcholine, but that it is inhibited by blocking the N1 receptor with hexamethonium. These findings indicate that neither the muscarinic receptor in the heart nor the nicotinic N2 receptor in skeletal muscle take part in regulation of glycogenolysis, which is connected with the action of acetylcholine on the cholinergic N1 receptor. Ganglioplegic compounds stimulate hydrolytic activity (hexamethonium, atropine in large doses)."} {"id": "PMID:1275665", "title": "Pharmacological analysis of regulation of phosphocreatine and ATP metabolism in resting skeletal muscle.", "content": "Phosphocreatine and ATP metabolism in the gastrocnemius muscle of rats was studied using 32P. Infusion of acetylcholine decreased utilization of energy in the resting muscle, probably as a result of lowered tonus of the resting muscle in analogy to the changes following muscle relaxation with tubocurarine or denervation. Isoprenaline, adrenaline and noradrenaline accelerated incorporation of 32P in phosphocreatine and ATP and depleted their reserves, and phenylephrine had an opposite effect. Ligation of the adrenals slowed the rate of this metabolism. Presumably regulation of energetic metabolism and energy consumption in resting skeletal muscle is dependent on two mechanisms, one of which is connected witly with liberation of adrenaline and its access to the muscle.", "contents": "Pharmacological analysis of regulation of phosphocreatine and ATP metabolism in resting skeletal muscle. Phosphocreatine and ATP metabolism in the gastrocnemius muscle of rats was studied using 32P. Infusion of acetylcholine decreased utilization of energy in the resting muscle, probably as a result of lowered tonus of the resting muscle in analogy to the changes following muscle relaxation with tubocurarine or denervation. Isoprenaline, adrenaline and noradrenaline accelerated incorporation of 32P in phosphocreatine and ATP and depleted their reserves, and phenylephrine had an opposite effect. Ligation of the adrenals slowed the rate of this metabolism. Presumably regulation of energetic metabolism and energy consumption in resting skeletal muscle is dependent on two mechanisms, one of which is connected witly with liberation of adrenaline and its access to the muscle."} {"id": "PMID:1275666", "title": "Interaction of basic polyvalent trypsin inhibitor before and after acetylation with DNA and carboxymethylcellulose.", "content": "1. The interaction of soluble complexes of DNA with basic polyvalent trypsin inhibitor of Kunitz's type before and after acetylation was studied. The ORD and CD spectra indicate that the secondary structure of DNA in complexes with protein undergoes marked alteration. 2. The Raman, ORD, CD and IR spectra showed that secondary structure of unmodified and acetylated polyvalent inhibitor in complexes with polyanoin undergoes marked alteration. Its content of alpha-spirals decreases, and content of beta-structure increases.", "contents": "Interaction of basic polyvalent trypsin inhibitor before and after acetylation with DNA and carboxymethylcellulose. 1. The interaction of soluble complexes of DNA with basic polyvalent trypsin inhibitor of Kunitz's type before and after acetylation was studied. The ORD and CD spectra indicate that the secondary structure of DNA in complexes with protein undergoes marked alteration. 2. The Raman, ORD, CD and IR spectra showed that secondary structure of unmodified and acetylated polyvalent inhibitor in complexes with polyanoin undergoes marked alteration. Its content of alpha-spirals decreases, and content of beta-structure increases."} {"id": "PMID:1275667", "title": "The effect of carboxymethylcellulose on antiproteolytic activity of unmodified, guanidylated and acetylated BPTI.", "content": "Acetylated BPTI loses its antitrypsin activity, but retains antichymotrypsin activity. Guanidylation diminishes the inhibitor's antitrypsin activity without affecting its antichymotrypsin activity. Acetylated inhibitor in complex with sodium salt of carboxymethylcellulose recovers antitrypsin activity which it did not have in the free state. Unmodified and guanidylated inhibitor in complex with CM-cellulose shows weaker antitrypsin as well as antichymotrypisn activity in comparison with free inhibitors.", "contents": "The effect of carboxymethylcellulose on antiproteolytic activity of unmodified, guanidylated and acetylated BPTI. Acetylated BPTI loses its antitrypsin activity, but retains antichymotrypsin activity. Guanidylation diminishes the inhibitor's antitrypsin activity without affecting its antichymotrypsin activity. Acetylated inhibitor in complex with sodium salt of carboxymethylcellulose recovers antitrypsin activity which it did not have in the free state. Unmodified and guanidylated inhibitor in complex with CM-cellulose shows weaker antitrypsin as well as antichymotrypisn activity in comparison with free inhibitors."} {"id": "PMID:1275669", "title": "Head injury in children and teenagers; functional recovery correlated with the duration of coma.", "content": "Residual impairments and mortality were assessed in 48 patients under 20 years of age at least two years after a traumatic head injury had caused coma lasting more than seven days. In this study the duration of coma was defined as the period of time when it is impossible to establish intellectual contact with the patient. A classification of functional levels 1 to 8 was used to identify the residual impairment and relate this impairment to the duration of coma for each patient. Of 30 patients who remained in coma less than three month, only one did not have independent ambulation with or without equipment at the time of his last follow-up evaluation. This was one parameter among others to show that the prognosis for recovery in this age group is much better than expected following severe head injury. These follow-up data, correlated with the duration of coma, can assist rehabilitation personnel in the prognostic planning for younger people with severe head injuries. Rehabilitation medicine needs to be involved in patient care during the period of coma to prevent contractures and other complications which often interfere with and delay later rehabilitation programs, making them more costly and less successful.", "contents": "Head injury in children and teenagers; functional recovery correlated with the duration of coma. Residual impairments and mortality were assessed in 48 patients under 20 years of age at least two years after a traumatic head injury had caused coma lasting more than seven days. In this study the duration of coma was defined as the period of time when it is impossible to establish intellectual contact with the patient. A classification of functional levels 1 to 8 was used to identify the residual impairment and relate this impairment to the duration of coma for each patient. Of 30 patients who remained in coma less than three month, only one did not have independent ambulation with or without equipment at the time of his last follow-up evaluation. This was one parameter among others to show that the prognosis for recovery in this age group is much better than expected following severe head injury. These follow-up data, correlated with the duration of coma, can assist rehabilitation personnel in the prognostic planning for younger people with severe head injuries. Rehabilitation medicine needs to be involved in patient care during the period of coma to prevent contractures and other complications which often interfere with and delay later rehabilitation programs, making them more costly and less successful."} {"id": "PMID:1275670", "title": "Electrodiagnosis of ulnar nerve lesions at the elbow.", "content": "To determine electrical criteria which might be helpful in the diagnosis of ulnar nerve entrapment at the elbow, clinical and electrodiagnostic features in 78 patients with suspected ulnar nerve entrapment at the elbow are described and compared to the results of sensory and motor conduction in the ulnar nerve in a control group of normal persons. These criteria include (1) absent or abnormal evoked sensory nerve action potential in the little finger, (2) motor conduction velocity of less than 45.0 meters/sec in across elbow segment of the ulnar nerve with elbow flexed at 35 degrees, and (3) abnormal electromyographic findings including the presence of increased insertional activity or signs of denervation in the first dorsal interosseous, abductor digiti minimi, and/or flexor carpi ulnaris muscles. Electromyographic abnormality was seen in 77.5% of patients with ulnar motor conduction velocity of less than 45.0 meters/sec across the elbow. The first dorsal interosseous was the most commonly affected muscle. A study of certain important anatomic and histologic factors, such as the arrangement and relative concentration of the motor and sensory fibers at certain key points inthe course of the ulnar nerve trunk, is necessary to understand the correlation between the clinicopathologic and electrodiagnostic features in patients with ulnar nerve entrapment at the elbow.", "contents": "Electrodiagnosis of ulnar nerve lesions at the elbow. To determine electrical criteria which might be helpful in the diagnosis of ulnar nerve entrapment at the elbow, clinical and electrodiagnostic features in 78 patients with suspected ulnar nerve entrapment at the elbow are described and compared to the results of sensory and motor conduction in the ulnar nerve in a control group of normal persons. These criteria include (1) absent or abnormal evoked sensory nerve action potential in the little finger, (2) motor conduction velocity of less than 45.0 meters/sec in across elbow segment of the ulnar nerve with elbow flexed at 35 degrees, and (3) abnormal electromyographic findings including the presence of increased insertional activity or signs of denervation in the first dorsal interosseous, abductor digiti minimi, and/or flexor carpi ulnaris muscles. Electromyographic abnormality was seen in 77.5% of patients with ulnar motor conduction velocity of less than 45.0 meters/sec across the elbow. The first dorsal interosseous was the most commonly affected muscle. A study of certain important anatomic and histologic factors, such as the arrangement and relative concentration of the motor and sensory fibers at certain key points inthe course of the ulnar nerve trunk, is necessary to understand the correlation between the clinicopathologic and electrodiagnostic features in patients with ulnar nerve entrapment at the elbow."} {"id": "PMID:1275671", "title": "Ultrasound coupling media: their relative transmissivity.", "content": "The relative transmissivities of several commonly used ultrasonic coupling agents were measured to determine if there were significant differences in their effectiveness. Coupling media were evaluated in thin films to simulate clinical use. In order to minimize experimental error in this determination, transmitted energy was measured in the far field of the sonating transducer; the receiving transducer was angled slightly to minimize standing waves; and the sonating chamber was made as anechoic as possible. It was found that there is no practical difference in the transmissivities of the common coupling agents, except that hydrocortisone ointments and creams had lower transmissivities, probably due to microscopically entrapped air. When used as a thin film, absorption of ultrasound in the media was insignificant, and variation in transducer pressure was found to cause differences in energy transmitted greater than those found between the common coupling media. Consequently, it was concluded that coupling media can be chosen primarily on the basis of cost and convenience.", "contents": "Ultrasound coupling media: their relative transmissivity. The relative transmissivities of several commonly used ultrasonic coupling agents were measured to determine if there were significant differences in their effectiveness. Coupling media were evaluated in thin films to simulate clinical use. In order to minimize experimental error in this determination, transmitted energy was measured in the far field of the sonating transducer; the receiving transducer was angled slightly to minimize standing waves; and the sonating chamber was made as anechoic as possible. It was found that there is no practical difference in the transmissivities of the common coupling agents, except that hydrocortisone ointments and creams had lower transmissivities, probably due to microscopically entrapped air. When used as a thin film, absorption of ultrasound in the media was insignificant, and variation in transducer pressure was found to cause differences in energy transmitted greater than those found between the common coupling media. Consequently, it was concluded that coupling media can be chosen primarily on the basis of cost and convenience."} {"id": "PMID:1275672", "title": "Fast and slow skeletal muscles: simultaneous in vitro study.", "content": "Simultaneous study of the function of fast and slow twitch skeletal muscles in the same in vitro preparation has obvious advantages. Equipment, method and technique are described for study of the soleus (slow) and extensor digitorum longus (fast) muscles from the mouse, and the problems involved in preparing and standardizing these studies are discussed. For nearly maximum function to be obtained from both muscles, careful attention must be given to the stimulus parameters used. Three separate studies were necessary to determine the appropriate stimulus duration, frequency and rest interval between the stimulus trains. The results indicate that for study of tetanic tension and rate of tension development of these muscles from the C57 NAB strain of mice at 20C the most satisfactory stimulus parameters are : duration 2 msec, frequency 100 pulses per second and duration of the stimulus train 700 msec. Rest interval between stimulus trains was two minutes as problems developed with rest intervals less than two minutes or greater than four minutes.", "contents": "Fast and slow skeletal muscles: simultaneous in vitro study. Simultaneous study of the function of fast and slow twitch skeletal muscles in the same in vitro preparation has obvious advantages. Equipment, method and technique are described for study of the soleus (slow) and extensor digitorum longus (fast) muscles from the mouse, and the problems involved in preparing and standardizing these studies are discussed. For nearly maximum function to be obtained from both muscles, careful attention must be given to the stimulus parameters used. Three separate studies were necessary to determine the appropriate stimulus duration, frequency and rest interval between the stimulus trains. The results indicate that for study of tetanic tension and rate of tension development of these muscles from the C57 NAB strain of mice at 20C the most satisfactory stimulus parameters are : duration 2 msec, frequency 100 pulses per second and duration of the stimulus train 700 msec. Rest interval between stimulus trains was two minutes as problems developed with rest intervals less than two minutes or greater than four minutes."} {"id": "PMID:1275673", "title": "Electrical stimulation and feedback training: effects on the voluntary control of paretic muscles.", "content": "The carry-over effect of gait-synchronized stimulation of the peroneal nerve on voluntary dorsiflexion of the paretic foot was evaluated in hemiplegic patients. The influence of providing audiovisual feedback of performance on voluntary control was also evaluated. Each patient received three test sessions separated at least one week apart. In each session, measurement of isometric torque from voluntary effort was repeated four times: before, and at 0, 30 and 60 minutes after a 20-minute walk period. Session 2 involved both peroneal stimulation during walking and performance feedback during voluntary efforts. Session 1 had stimulation only. Session 3 had feedback only. The results were inconsistent among the patients. Where increase of voluntary dorsiflexion was obtained, it was more a consequence of performance feedback than peroneal stimulation. General problems of using isometric torque produced by voluntary dorsiflexion as a measure of the carry-over effect are discussed.", "contents": "Electrical stimulation and feedback training: effects on the voluntary control of paretic muscles. The carry-over effect of gait-synchronized stimulation of the peroneal nerve on voluntary dorsiflexion of the paretic foot was evaluated in hemiplegic patients. The influence of providing audiovisual feedback of performance on voluntary control was also evaluated. Each patient received three test sessions separated at least one week apart. In each session, measurement of isometric torque from voluntary effort was repeated four times: before, and at 0, 30 and 60 minutes after a 20-minute walk period. Session 2 involved both peroneal stimulation during walking and performance feedback during voluntary efforts. Session 1 had stimulation only. Session 3 had feedback only. The results were inconsistent among the patients. Where increase of voluntary dorsiflexion was obtained, it was more a consequence of performance feedback than peroneal stimulation. General problems of using isometric torque produced by voluntary dorsiflexion as a measure of the carry-over effect are discussed."} {"id": "PMID:1275674", "title": "Conditioning program for amputees with significant heart disease.", "content": "A program has been developed for training amputees with significant heart disease. In seven patients, a stress test was performed to evaluate cardiac functional capacity and heart rate response, utilizing both invasive and noninvasive techniques. Following this test, a conditioning program was instituted to improve cardiovascular function. At discharge and six week follow-up, all patients were able to ambulate at least 90 feet (27.4 meters) without excessive pulse rise or cardiac symptoms. This study demonstrates that by proper application of the principles of exercise physiology and cardiac pathophysiology, one should not necessarily deny a disabled patient wiith significant heart disease the opportunity to participate in a rehabilitation program.", "contents": "Conditioning program for amputees with significant heart disease. A program has been developed for training amputees with significant heart disease. In seven patients, a stress test was performed to evaluate cardiac functional capacity and heart rate response, utilizing both invasive and noninvasive techniques. Following this test, a conditioning program was instituted to improve cardiovascular function. At discharge and six week follow-up, all patients were able to ambulate at least 90 feet (27.4 meters) without excessive pulse rise or cardiac symptoms. This study demonstrates that by proper application of the principles of exercise physiology and cardiac pathophysiology, one should not necessarily deny a disabled patient wiith significant heart disease the opportunity to participate in a rehabilitation program."} {"id": "PMID:1275675", "title": "Medical recommendations--followed or ignored? Factors influencing compliance in arthritis.", "content": "Physiatrists are frequently confronted by the failure of patients to follow medical advice, with resultant adverse effects on rehabilitation outcomes. This paper examines the compliance of arthritis patients with an exercise regimen. A number of factors are examined in this study in assessing elements related to patient compliance. Included are patient attributes and perceptions, professional home visits and form of instruction in the regimen and selected features of the patient's social environment. Age, activity status and marital status, use of medications, patient understanding of arthritis and professional home visits appear to have a bearing upon patient compliance. Careful attention to factors likely to influence patient compliance will prove helpful in efforts designed to enhance rehabilitative progress and, ultimately, improve the lives of patients.", "contents": "Medical recommendations--followed or ignored? Factors influencing compliance in arthritis. Physiatrists are frequently confronted by the failure of patients to follow medical advice, with resultant adverse effects on rehabilitation outcomes. This paper examines the compliance of arthritis patients with an exercise regimen. A number of factors are examined in this study in assessing elements related to patient compliance. Included are patient attributes and perceptions, professional home visits and form of instruction in the regimen and selected features of the patient's social environment. Age, activity status and marital status, use of medications, patient understanding of arthritis and professional home visits appear to have a bearing upon patient compliance. Careful attention to factors likely to influence patient compliance will prove helpful in efforts designed to enhance rehabilitative progress and, ultimately, improve the lives of patients."} {"id": "PMID:1275677", "title": "Bio-behavioral monitoring: a method for remote health measurement.", "content": "The treatment of chronic disease has been severely limited by the failure to develop a technology of self-measurement. To examine and validate remotely acquired data from ambulatory patients, 13 cirrhotic subjects were asked to make daily measurements of medically and behaviorally significant variables. Subjects transmitted data for six months on variables such as weight, alcohol consumption, medications, hours worked, liquid consumed and general activity, complying with 90.4% (10,078) of the requests for data. Highly significant relationships were found between patients' reports and criterion measures of weight data and alcohol consumption. Significant negative relationships between hours worked and alcohol consumption were found for several patients (P less than 0.001). The results suggest that ambulatory patients can systematically measure and communicate medically and behaviorally significant information.", "contents": "Bio-behavioral monitoring: a method for remote health measurement. The treatment of chronic disease has been severely limited by the failure to develop a technology of self-measurement. To examine and validate remotely acquired data from ambulatory patients, 13 cirrhotic subjects were asked to make daily measurements of medically and behaviorally significant variables. Subjects transmitted data for six months on variables such as weight, alcohol consumption, medications, hours worked, liquid consumed and general activity, complying with 90.4% (10,078) of the requests for data. Highly significant relationships were found between patients' reports and criterion measures of weight data and alcohol consumption. Significant negative relationships between hours worked and alcohol consumption were found for several patients (P less than 0.001). The results suggest that ambulatory patients can systematically measure and communicate medically and behaviorally significant information."} {"id": "PMID:1275678", "title": "Hand orthotic device influence on fine neuromuscular control.", "content": "With the aid of electromyography, voluntary control of fine neuromuscular activity of deltoid and extensor digitorum communis muscles was studied in patients with motor dysfunction of the upper limb. A sequential training procedure was carried out both while the patient was wearing and not wearing a hand orthosis, during a static posture and dynamic hand movements. There was no difference between the levels of neuromuscular control achieved while wearing and not wearing the orthotic device, but the quality of the neuromuscular control was superior in the proximal limb muscle to that in the more distal muscle.", "contents": "Hand orthotic device influence on fine neuromuscular control. With the aid of electromyography, voluntary control of fine neuromuscular activity of deltoid and extensor digitorum communis muscles was studied in patients with motor dysfunction of the upper limb. A sequential training procedure was carried out both while the patient was wearing and not wearing a hand orthosis, during a static posture and dynamic hand movements. There was no difference between the levels of neuromuscular control achieved while wearing and not wearing the orthotic device, but the quality of the neuromuscular control was superior in the proximal limb muscle to that in the more distal muscle."} {"id": "PMID:1275679", "title": "Sweating responses of normal, paraplegic and anhidrotic subjects.", "content": "Dynamic sudomotor response to changing ambient temperatures (30 C to 45 C) was measured on eight unacclimatized subjects including five normals, two paraplegics and one anhidrotic patient. Mean sweating rates, computed from five simultaneously observed local rates, were used to compare the overall sudomotor response to heat exposure of the three groups. In the normal subjects, an average rise of 0.34 C in oral temperature and 2.5 C in mean skin temperature was found in a period of 65 minutes. The paraplegics developed a higher rise in both oral and skin temperatures due to a lower sweating rate in the insentinent region. (Insentient describes the sensory state of the skin below the level of the lesion where the subject has no awareness of surface stimulation). A relatively higher sweating rate was observed on the forehead and the cyclic sweating behavior of the insentient skin was not synchronous with that in the sentient. (Sentient describes the state where partial or total awareness is elicited by stimulation). The anhidrotic patient showed a twofold increase of moisture loss from the skin but no cyclic pattern of sweat gland activity on exposure to heat. In this case, hyperthermia developed with a rise in oral temperature of 1.1 C in 52 minutes versus 0.4 C rise in the controls in a period of 63 minutes.", "contents": "Sweating responses of normal, paraplegic and anhidrotic subjects. Dynamic sudomotor response to changing ambient temperatures (30 C to 45 C) was measured on eight unacclimatized subjects including five normals, two paraplegics and one anhidrotic patient. Mean sweating rates, computed from five simultaneously observed local rates, were used to compare the overall sudomotor response to heat exposure of the three groups. In the normal subjects, an average rise of 0.34 C in oral temperature and 2.5 C in mean skin temperature was found in a period of 65 minutes. The paraplegics developed a higher rise in both oral and skin temperatures due to a lower sweating rate in the insentinent region. (Insentient describes the sensory state of the skin below the level of the lesion where the subject has no awareness of surface stimulation). A relatively higher sweating rate was observed on the forehead and the cyclic sweating behavior of the insentient skin was not synchronous with that in the sentient. (Sentient describes the state where partial or total awareness is elicited by stimulation). The anhidrotic patient showed a twofold increase of moisture loss from the skin but no cyclic pattern of sweat gland activity on exposure to heat. In this case, hyperthermia developed with a rise in oral temperature of 1.1 C in 52 minutes versus 0.4 C rise in the controls in a period of 63 minutes."} {"id": "PMID:1275681", "title": "Hip abnormalities in cerebral palsy: radiological study.", "content": "A total of 237 hips of children with cerebral palsy were examined annually for three years. The severely involved spastic children and those who had never stood were more susceptible to hip abnormality. Apparent coxa valga (whose phenotype consists more of anteversion and less of true coxa valga) is closely related to the hip abnormality.", "contents": "Hip abnormalities in cerebral palsy: radiological study. A total of 237 hips of children with cerebral palsy were examined annually for three years. The severely involved spastic children and those who had never stood were more susceptible to hip abnormality. Apparent coxa valga (whose phenotype consists more of anteversion and less of true coxa valga) is closely related to the hip abnormality."} {"id": "PMID:1275682", "title": "Sexual loss in relation to other functional losses for spinal cord injured males.", "content": "To understand more fully the importance of sexual loss for spinal cord injured patients, paraplegic and quadriplegic men were asked to rank order functional losses associated with their respective injuries. In addition, staff members of the rehabilitation team were asked to predict the relative importance of these functional losses to their cord injured patients. The data indicate that relative to actual patient perceptions, staff predictions tended to overemphasize the relative importance of normal genital sexual functioning. Some implications of these findings for comprehensive rehabilitation programs are discussed.", "contents": "Sexual loss in relation to other functional losses for spinal cord injured males. To understand more fully the importance of sexual loss for spinal cord injured patients, paraplegic and quadriplegic men were asked to rank order functional losses associated with their respective injuries. In addition, staff members of the rehabilitation team were asked to predict the relative importance of these functional losses to their cord injured patients. The data indicate that relative to actual patient perceptions, staff predictions tended to overemphasize the relative importance of normal genital sexual functioning. Some implications of these findings for comprehensive rehabilitation programs are discussed."} {"id": "PMID:1275683", "title": "A miniaturized load cell for lower extremity amputees.", "content": "The PRS-Moore Load Cell for below-knee and above-knee amputees that gives an audible warning when the wearer applies more than the predetermined weight on the affected limb is described. The sensing unit is a screw-adjustable compression spring that is enclosed in a machined housing that fits inside a machined base. Several prototypes have been produced and are now undergoing clinical analysis.", "contents": "A miniaturized load cell for lower extremity amputees. The PRS-Moore Load Cell for below-knee and above-knee amputees that gives an audible warning when the wearer applies more than the predetermined weight on the affected limb is described. The sensing unit is a screw-adjustable compression spring that is enclosed in a machined housing that fits inside a machined base. Several prototypes have been produced and are now undergoing clinical analysis."} {"id": "PMID:1275684", "title": "Body composition changes in women: effects of high and low exercise intensity.", "content": "Twenty college-age women participated in a ten-week physical training program involving two intensities of exercise. Eleven women trained at a relatively high exercise intensity (HI) of 840 kgm/min while nine women trained at a low exercise intensity (LI) of 420 kgm/min. Body composition and residual lung volume changes were analyzed before and after the training program for both groups. There were no significant changes in body weight, body density, percent body fat, lean body weight and residual lung volume for the HI group. The LI group exhibited a significant increase in body density (0.0026 density units) and significant decreases in percent fat (1.1%) and residual lung volume (67 ml). Closed circuit metabolic measures indicated that the HI group was working anaerobically for at least a portion of each minute. Results of the study support the contention that to reduce body fat stores an exercise program of low intensity and long duration is required.", "contents": "Body composition changes in women: effects of high and low exercise intensity. Twenty college-age women participated in a ten-week physical training program involving two intensities of exercise. Eleven women trained at a relatively high exercise intensity (HI) of 840 kgm/min while nine women trained at a low exercise intensity (LI) of 420 kgm/min. Body composition and residual lung volume changes were analyzed before and after the training program for both groups. There were no significant changes in body weight, body density, percent body fat, lean body weight and residual lung volume for the HI group. The LI group exhibited a significant increase in body density (0.0026 density units) and significant decreases in percent fat (1.1%) and residual lung volume (67 ml). Closed circuit metabolic measures indicated that the HI group was working anaerobically for at least a portion of each minute. Results of the study support the contention that to reduce body fat stores an exercise program of low intensity and long duration is required."} {"id": "PMID:1275687", "title": "Cultural factors affecting urban Mexican male homosexual behavior.", "content": "Some aspects of the mestizoized urban culture in Mexico are linked to male homosexuality in support of the theory that cultural factors play an important role in the kind of life styles and sex practices of males involved in homosexual behavior. The following factors are considered relevant: the sharp dichotomization of gender roles, dual categorization of females as good or bad, separate social networks maintained by males before and after marriage, proportion of unmarried males, and distribution of income. One result of the sharp dichotomization of male and female gender roles is the widely held belief that effeminate males generally prefer to play the female role rather than the male. Effeminacy and homosexuality are also linked by the belief that as a result of this role preference effeminate males are sexually interested only in masculine males with whom they play the passive sex role. The participation of masculine males in homosexual encounters is related in part to a relatively high level of sexual awareness in combination with the lack of stigmatization of the insertor sex role and in part to the restraints placed on alternative sexual outlets by available income and/or marital status. Males involved in homosexual behavior in Mexico operate in a sociocultural environment which gives rise to expectations that they should play either the insertee or insertor sex role but not both and that they should obtain ultimate sexual satisfaction with anal intercourse rather than fellatio. In spite of cultural imperatives, however, individual preferences stemming from other variables such as personality needs, sexual gratification, desires of wanted partners, and amount of involvement may override the imperatives with resulting variations in sexual behavior patterns.", "contents": "Cultural factors affecting urban Mexican male homosexual behavior. Some aspects of the mestizoized urban culture in Mexico are linked to male homosexuality in support of the theory that cultural factors play an important role in the kind of life styles and sex practices of males involved in homosexual behavior. The following factors are considered relevant: the sharp dichotomization of gender roles, dual categorization of females as good or bad, separate social networks maintained by males before and after marriage, proportion of unmarried males, and distribution of income. One result of the sharp dichotomization of male and female gender roles is the widely held belief that effeminate males generally prefer to play the female role rather than the male. Effeminacy and homosexuality are also linked by the belief that as a result of this role preference effeminate males are sexually interested only in masculine males with whom they play the passive sex role. The participation of masculine males in homosexual encounters is related in part to a relatively high level of sexual awareness in combination with the lack of stigmatization of the insertor sex role and in part to the restraints placed on alternative sexual outlets by available income and/or marital status. Males involved in homosexual behavior in Mexico operate in a sociocultural environment which gives rise to expectations that they should play either the insertee or insertor sex role but not both and that they should obtain ultimate sexual satisfaction with anal intercourse rather than fellatio. In spite of cultural imperatives, however, individual preferences stemming from other variables such as personality needs, sexual gratification, desires of wanted partners, and amount of involvement may override the imperatives with resulting variations in sexual behavior patterns."} {"id": "PMID:1275688", "title": "Orgasmic frequency and plasma testosterone levels in normal human males.", "content": "Twenty males participated in a 2-month study examining the relationship between 8 a.m. plasma testosterone levels and orgasmic frequency. Within subjects, higher levels of testosterone are associated with periods of sexual activity. Over subjects, however, the direction of the relationship is reversed. Mean testosterone levels were higher for sexually less active individuals.", "contents": "Orgasmic frequency and plasma testosterone levels in normal human males. Twenty males participated in a 2-month study examining the relationship between 8 a.m. plasma testosterone levels and orgasmic frequency. Within subjects, higher levels of testosterone are associated with periods of sexual activity. Over subjects, however, the direction of the relationship is reversed. Mean testosterone levels were higher for sexually less active individuals."} {"id": "PMID:1275689", "title": "Masturbation and sexual fantasies in married couples.", "content": "This article reports some aspects of sociosexual behavior, as a small part of an intensive study of 38 married couples. The persons' experiences and formulations are the primary material in an effort to humanize sexological research. This article reflects the Danish psychological-psychiatric tradition with emphasis on personal interviews instead of questionnaires, inventories, or tests. The analyses are based on differences between husband and wife and between men and women as groups. A number of qualitative thematic differences in personal experience with respect to masturbation and sexual fantasies are reported. Attention is drawn to thematic differences in the psychological significance of these aspects of sexuality which are, in part, dependent on the sex of the subject.", "contents": "Masturbation and sexual fantasies in married couples. This article reports some aspects of sociosexual behavior, as a small part of an intensive study of 38 married couples. The persons' experiences and formulations are the primary material in an effort to humanize sexological research. This article reflects the Danish psychological-psychiatric tradition with emphasis on personal interviews instead of questionnaires, inventories, or tests. The analyses are based on differences between husband and wife and between men and women as groups. A number of qualitative thematic differences in personal experience with respect to masturbation and sexual fantasies are reported. Attention is drawn to thematic differences in the psychological significance of these aspects of sexuality which are, in part, dependent on the sex of the subject."} {"id": "PMID:1275690", "title": "Personality correlates of male sexual arousal and behavior.", "content": "This study explores the relationship between male sexual behavior and personality factors, as measured by the MMPI and Sensation Seeking Scale. Subjects were 20 male volunteers, ages 19-58, with a history of long-term sexual relationships. Subjects kept a daily record of sexual behaviors. Frequency of these behaviors was correlated with MMPI and Sensation Seeking (SSS) subscales. Results indicate that both introversion and depression show significant correlations with autoerotic stimulation and arousal, but not with heterosexual activity. There is no significant correlation demonstrated between hypomania and sexual activity. The Boredom Susceptibility subscale of the SSS correlated significantly with the number of sexual partners.", "contents": "Personality correlates of male sexual arousal and behavior. This study explores the relationship between male sexual behavior and personality factors, as measured by the MMPI and Sensation Seeking Scale. Subjects were 20 male volunteers, ages 19-58, with a history of long-term sexual relationships. Subjects kept a daily record of sexual behaviors. Frequency of these behaviors was correlated with MMPI and Sensation Seeking (SSS) subscales. Results indicate that both introversion and depression show significant correlations with autoerotic stimulation and arousal, but not with heterosexual activity. There is no significant correlation demonstrated between hypomania and sexual activity. The Boredom Susceptibility subscale of the SSS correlated significantly with the number of sexual partners."} {"id": "PMID:1275691", "title": "Women among men: females in the male homosexual community.", "content": "The study uses empirical data to generate a preliminary theoretical analysis of the types of interaction and relationships that exist between male homosexuals on the one hand and lesbians and female heterosexuals on the other. Both males' and females' accounts of why they associate with one another in the male gay community are also examined. Methods appropriate to the description of interaction and the collection of accounts of behavior were used: participant observation and interviewing.", "contents": "Women among men: females in the male homosexual community. The study uses empirical data to generate a preliminary theoretical analysis of the types of interaction and relationships that exist between male homosexuals on the one hand and lesbians and female heterosexuals on the other. Both males' and females' accounts of why they associate with one another in the male gay community are also examined. Methods appropriate to the description of interaction and the collection of accounts of behavior were used: participant observation and interviewing."} {"id": "PMID:1275692", "title": "Bisexuality in women.", "content": "In-depth interviews with women having a history of bisexual behavior and/or a bisexual self-identification revealed only moderate correspondence between behavior and identity. A general description is provided of the sexual relationships of the respondents. The major focus is on the wide diversity of self-identified bisexual women, especially in terms of self-perceived sexual and emotional needs, circumstances precipitating heterosexual and homosexual behavior, and ideological supports for a bisexual life style. Heterosexual behavior among homosexual women is discussed in terms of economic necessity, experimentation, and the response of the lesbian community. Homosexual behavior among heterosexual women is discussed in terms of responses to different kinds of situational exigencies and the rationalizations used to deal with the experience while insulating the heterosexual self-identification.", "contents": "Bisexuality in women. In-depth interviews with women having a history of bisexual behavior and/or a bisexual self-identification revealed only moderate correspondence between behavior and identity. A general description is provided of the sexual relationships of the respondents. The major focus is on the wide diversity of self-identified bisexual women, especially in terms of self-perceived sexual and emotional needs, circumstances precipitating heterosexual and homosexual behavior, and ideological supports for a bisexual life style. Heterosexual behavior among homosexual women is discussed in terms of economic necessity, experimentation, and the response of the lesbian community. Homosexual behavior among heterosexual women is discussed in terms of responses to different kinds of situational exigencies and the rationalizations used to deal with the experience while insulating the heterosexual self-identification."} {"id": "PMID:1275695", "title": "Cervical spine injuries. Diagnosis and classification.", "content": "Roentogenographic techniques in the evaluation of the patient with a cervical spine injury entail several considerations that should be respected in defining and classifying the lesion according to the mechanism of injury. Unilateral or bilateral facet dislocation with separation of posterior elements usually implies disruptive flexion injury. Anterior wedging of a vertebral body indicates flexion with some degree of compression. Comminution of the vertebral body indicates a predominant compressive element to the injury. An anterior-inferior marginal fracture indicates extension injury. Impaction of the inferior articulating processes or fracture of the pedicle producing a more horizontal appearance of the facet indicates disruption of interspinous ligaments and the probability that significant instability exists. Studies should not be terminated until complete visualization of all cervical segments has been obtained, including the cervico-thoracic junction.", "contents": "Cervical spine injuries. Diagnosis and classification. Roentogenographic techniques in the evaluation of the patient with a cervical spine injury entail several considerations that should be respected in defining and classifying the lesion according to the mechanism of injury. Unilateral or bilateral facet dislocation with separation of posterior elements usually implies disruptive flexion injury. Anterior wedging of a vertebral body indicates flexion with some degree of compression. Comminution of the vertebral body indicates a predominant compressive element to the injury. An anterior-inferior marginal fracture indicates extension injury. Impaction of the inferior articulating processes or fracture of the pedicle producing a more horizontal appearance of the facet indicates disruption of interspinous ligaments and the probability that significant instability exists. Studies should not be terminated until complete visualization of all cervical segments has been obtained, including the cervico-thoracic junction."} {"id": "PMID:1275696", "title": "Surgical stabilization of the cervical spine after trauma.", "content": "Surgical stabilization should be individualized for each patient. The procedure used should provide both immediate and prolonged stability at the site of instability. The choice of procedure depends on knowledge of the structures providing stability and of the mechanism of injury. Pure flexon injuries without comminution or disruption of ligaments are stable and do not require surgical treatment. Flexion-rotation dislocations, with either unilateral or bilateral facet dislocation, should be treated by posterior open reduction and fusion if they cannot be reduced by a closed method or if there is demonstratable motion on three-month flexion-extension roentgenograms. A comminuted burst (\"teardrop\") fracture produced by axial loading of the vertebral bodies should be stabilized by an anterior cortical strut graft for early mobilization and realignment of the spinal column to prevent progressive deformity.", "contents": "Surgical stabilization of the cervical spine after trauma. Surgical stabilization should be individualized for each patient. The procedure used should provide both immediate and prolonged stability at the site of instability. The choice of procedure depends on knowledge of the structures providing stability and of the mechanism of injury. Pure flexon injuries without comminution or disruption of ligaments are stable and do not require surgical treatment. Flexion-rotation dislocations, with either unilateral or bilateral facet dislocation, should be treated by posterior open reduction and fusion if they cannot be reduced by a closed method or if there is demonstratable motion on three-month flexion-extension roentgenograms. A comminuted burst (\"teardrop\") fracture produced by axial loading of the vertebral bodies should be stabilized by an anterior cortical strut graft for early mobilization and realignment of the spinal column to prevent progressive deformity."} {"id": "PMID:1275697", "title": "Congenital causes of duodenal ulcers in adults.", "content": "In seven cases of congenital anomalies in adults, duodenal obstruction and peptic ulcer disease developed. There were two cases of congenital duodenal web, two of hypertrophic pyloric stenosis, two of annular pancreas, and one of a preduodenal portal vein. The diagnosis is seldom made preoperatively. In the four patients who had preoperative gastric analysis, the acid secretions were increased. Those patients who underwent endoscopy had changes consistent with hypertrophic secretory gastrophy and duodenitis. We believe that treatment should be directed toward relief of the duodenal obstruction and the reduction of basal acid secretion by truncal vagotomy in all such cases.", "contents": "Congenital causes of duodenal ulcers in adults. In seven cases of congenital anomalies in adults, duodenal obstruction and peptic ulcer disease developed. There were two cases of congenital duodenal web, two of hypertrophic pyloric stenosis, two of annular pancreas, and one of a preduodenal portal vein. The diagnosis is seldom made preoperatively. In the four patients who had preoperative gastric analysis, the acid secretions were increased. Those patients who underwent endoscopy had changes consistent with hypertrophic secretory gastrophy and duodenitis. We believe that treatment should be directed toward relief of the duodenal obstruction and the reduction of basal acid secretion by truncal vagotomy in all such cases."} {"id": "PMID:1275698", "title": "Esophageal disruption from blunt and penetrating external trauma.", "content": "Eleven patients suffered esophageal perforations from external trauma. This series includes the first report of esophageal perforation that resulted from a cervical flexion-hyperextension injury. The other ten patient had penetrating trauma. Early signs were subtle. Small amounts of mediastinal and cervical air tended to be overlooked or erroneously attributed to other causes, such as associated pneumothorax. Once suspected, the possibility of esophageal disruption was not always pursued with optimum vigor. There was undue reliance on contrast media radiography. There were two patients with falsely normal esophagograms. All patients healed well when treated witreatment of choice.", "contents": "Esophageal disruption from blunt and penetrating external trauma. Eleven patients suffered esophageal perforations from external trauma. This series includes the first report of esophageal perforation that resulted from a cervical flexion-hyperextension injury. The other ten patient had penetrating trauma. Early signs were subtle. Small amounts of mediastinal and cervical air tended to be overlooked or erroneously attributed to other causes, such as associated pneumothorax. Once suspected, the possibility of esophageal disruption was not always pursued with optimum vigor. There was undue reliance on contrast media radiography. There were two patients with falsely normal esophagograms. All patients healed well when treated witreatment of choice."} {"id": "PMID:1275699", "title": "The pros and cons of outpatient breast biopsy.", "content": "A review of the 130 breast biopsies performed on women during the past three years at the Martin Luther King, Jr, General Hospital showed that 90 were performed on outpatients and 40 on inpatients. Of the 90 outpatient procedures, 61 were under local anesthesia and 29 under general. Only three outpatient biopsy specimens were malignant and required subsequent patient admission to the hospital for mastectomy at an interval of 9 to 14 days. In all three, the axillary nodes were uninvolved. In two, no residual tumor was found in the mastectomy specimen.", "contents": "The pros and cons of outpatient breast biopsy. A review of the 130 breast biopsies performed on women during the past three years at the Martin Luther King, Jr, General Hospital showed that 90 were performed on outpatients and 40 on inpatients. Of the 90 outpatient procedures, 61 were under local anesthesia and 29 under general. Only three outpatient biopsy specimens were malignant and required subsequent patient admission to the hospital for mastectomy at an interval of 9 to 14 days. In all three, the axillary nodes were uninvolved. In two, no residual tumor was found in the mastectomy specimen."} {"id": "PMID:1275700", "title": "Delayed vein repositioning. A procedure for improving inadequate radial-cephalic arteriovenous fistulas.", "content": "Patients undergoing hemodialysis, whose radial-cephalic arteriovenous fistulas (RCAVFs) were unsatisfactory because of poor accessibility, were treated by surgical repositioning of the full length of arterialized cephalic vein in the forearm. Marked improvement in accessibility for more than one year was achieved in 15 of 18 delayed venous repositioning operations. This procedure is recommended for improving certain types of inadequate RCAVF.", "contents": "Delayed vein repositioning. A procedure for improving inadequate radial-cephalic arteriovenous fistulas. Patients undergoing hemodialysis, whose radial-cephalic arteriovenous fistulas (RCAVFs) were unsatisfactory because of poor accessibility, were treated by surgical repositioning of the full length of arterialized cephalic vein in the forearm. Marked improvement in accessibility for more than one year was achieved in 15 of 18 delayed venous repositioning operations. This procedure is recommended for improving certain types of inadequate RCAVF."} {"id": "PMID:1275701", "title": "Carcinoma of the colon and rectum. A review of results of surgical treatment in 164 patients.", "content": "This report is a retrospective review of the authors' experience with colonic and rectal carcinoma in 164 patients from 1954 to 1968 with a five-year follow-up. The operative approach utilized principles of early vascular isolation, wied-colon and mesenteric reseciton, and minimal tumor manipulation in curative operations; palliative procedures were aggressively employed. Of the 164 patients, 104 with lesions almost equally divided between colon and rectum had resections with curative intent. The overall five-year survival rate after curative resection was 55%, and included eight hospital deaths that were usually related to cardiopulmonary complications. Lymph node involvement appreciably decreased the survival rate from 72% without node involvement to 39% with node involvement. Patients with rectal lesions experienced more favorable results than those with colonic lesions. Palliative procedures in 46 patients enhanced comfort, but few patients survived longer than one year. Wound and anastomotic complications were infrequent.", "contents": "Carcinoma of the colon and rectum. A review of results of surgical treatment in 164 patients. This report is a retrospective review of the authors' experience with colonic and rectal carcinoma in 164 patients from 1954 to 1968 with a five-year follow-up. The operative approach utilized principles of early vascular isolation, wied-colon and mesenteric reseciton, and minimal tumor manipulation in curative operations; palliative procedures were aggressively employed. Of the 164 patients, 104 with lesions almost equally divided between colon and rectum had resections with curative intent. The overall five-year survival rate after curative resection was 55%, and included eight hospital deaths that were usually related to cardiopulmonary complications. Lymph node involvement appreciably decreased the survival rate from 72% without node involvement to 39% with node involvement. Patients with rectal lesions experienced more favorable results than those with colonic lesions. Palliative procedures in 46 patients enhanced comfort, but few patients survived longer than one year. Wound and anastomotic complications were infrequent."} {"id": "PMID:1275702", "title": "Traumatic rupture of thoracic aorta. Diagnosis and management.", "content": "Of six cases of thoracic aortic rupture, four were acute and two were chronic. In the four acute cases, suspicious findings were an appreciably widened mediastinum, upper-extremity hypertension, change in pulse amplitude, or, more hopefully, generalized hypertension, left intraclavicular systolic murmur, and loss of posterior aortic shadow on chest x-ray film. Preoperative angiography was essential. Three of four acute aortic transections (one with aortic arch involvement) had complicated associated injuries that necessitated delay in aortic surgical repair; antihypertensive drugs, including propranolol hydrochloride, were used for support in the interval. Perfusion by femoral vein-femoral artery cardiopulmonary bypass was used. All four patients were operated on successfully without residual complications. Two patients with chronic conditions were recommended for surgery; one was successfully operated on, using aorto-aortic bypass. Another patient, 27 years postinjury, refused operation. Postoperative arteriograms were performed for baseline observations of graft and suture-line characteristics in all cases.", "contents": "Traumatic rupture of thoracic aorta. Diagnosis and management. Of six cases of thoracic aortic rupture, four were acute and two were chronic. In the four acute cases, suspicious findings were an appreciably widened mediastinum, upper-extremity hypertension, change in pulse amplitude, or, more hopefully, generalized hypertension, left intraclavicular systolic murmur, and loss of posterior aortic shadow on chest x-ray film. Preoperative angiography was essential. Three of four acute aortic transections (one with aortic arch involvement) had complicated associated injuries that necessitated delay in aortic surgical repair; antihypertensive drugs, including propranolol hydrochloride, were used for support in the interval. Perfusion by femoral vein-femoral artery cardiopulmonary bypass was used. All four patients were operated on successfully without residual complications. Two patients with chronic conditions were recommended for surgery; one was successfully operated on, using aorto-aortic bypass. Another patient, 27 years postinjury, refused operation. Postoperative arteriograms were performed for baseline observations of graft and suture-line characteristics in all cases."} {"id": "PMID:1275703", "title": "An evaluation of mediastinoscopy as a guide to diagnosis and therapy.", "content": "A retrospective study was made of 230 consecutive unselected mediastinoscopies done during the years 1969 through 1975 in an attempt to identify guidelines for selective use of mediastinoscopy. Findings at mediastinoscopy were correlated with pathologic diagnosis, location and size of the lesion, presence or absence of enlarged lymph nodes on chest x-ray film, and findings at subsequent thoractomy when performed. On the basis of this review, the following lesions seem amenable to diagnosis at mediastinoscopy: bilateral hilar adenopathy (24 of 25 in this study); central lesions (30 of 45); peripheral lesions with adenopathy seen on x-ray film (nine of 22); and infiltrates (eight of 24). Mediastinoscopy is not recommended for peripheral lesions without adenopathy seen on x-ray film.", "contents": "An evaluation of mediastinoscopy as a guide to diagnosis and therapy. A retrospective study was made of 230 consecutive unselected mediastinoscopies done during the years 1969 through 1975 in an attempt to identify guidelines for selective use of mediastinoscopy. Findings at mediastinoscopy were correlated with pathologic diagnosis, location and size of the lesion, presence or absence of enlarged lymph nodes on chest x-ray film, and findings at subsequent thoractomy when performed. On the basis of this review, the following lesions seem amenable to diagnosis at mediastinoscopy: bilateral hilar adenopathy (24 of 25 in this study); central lesions (30 of 45); peripheral lesions with adenopathy seen on x-ray film (nine of 22); and infiltrates (eight of 24). Mediastinoscopy is not recommended for peripheral lesions without adenopathy seen on x-ray film."} {"id": "PMID:1275704", "title": "Permanent atrial pacing. Epicardial approach - \"pinch-on\" electrodes.", "content": "Atrial pacing, while recognized to have therapeutic indications, has not been easily accomplished because there have been no simple and reliable electrodes available. A short parasternal mediastinotomy provides sufficient exposure for easy application of \"pinch-on\" electrodes to the presenting fold of the right atrium. Special attention is given to the recording of electrical indexes of the pulse generator and electrodes (voltage threshold, calculated impedance, and intrinsic amplitude of the P wave) with testing apparatus, most of which is conveniently brought to the operative table. Less than ideal results are not accepted, and immediate replacement of the electrodes into adjacent areas of the atrial myocardium is performed with ease. Five patients have tolerated the procedure without complication. These electrodes and this operative procedure have proved to have been successful over a six-month term of observation.", "contents": "Permanent atrial pacing. Epicardial approach - \"pinch-on\" electrodes. Atrial pacing, while recognized to have therapeutic indications, has not been easily accomplished because there have been no simple and reliable electrodes available. A short parasternal mediastinotomy provides sufficient exposure for easy application of \"pinch-on\" electrodes to the presenting fold of the right atrium. Special attention is given to the recording of electrical indexes of the pulse generator and electrodes (voltage threshold, calculated impedance, and intrinsic amplitude of the P wave) with testing apparatus, most of which is conveniently brought to the operative table. Less than ideal results are not accepted, and immediate replacement of the electrodes into adjacent areas of the atrial myocardium is performed with ease. Five patients have tolerated the procedure without complication. These electrodes and this operative procedure have proved to have been successful over a six-month term of observation."} {"id": "PMID:1275705", "title": "Division of the pyriformis muscle for the treatment of sciatica. Postlaminectomy syndrome and osteoarthritis of the spine.", "content": "Division of the pyriformis muscle at its tendinous insertion was employed for the treatment of sciatica in 14 patients with postlaminectomy syndrome and osteoarthritis of the spine. Of these patients, 85% had satisfactory results. It is logical that the pyriformis muscle can play an important role in the production of sciatic associated with intraspinal lesions. Tension on the sciatic nerve, which passes in close approximation to the pyriformis muscle anteriorly, can be relieved by division of the pyriformis muscle.", "contents": "Division of the pyriformis muscle for the treatment of sciatica. Postlaminectomy syndrome and osteoarthritis of the spine. Division of the pyriformis muscle at its tendinous insertion was employed for the treatment of sciatica in 14 patients with postlaminectomy syndrome and osteoarthritis of the spine. Of these patients, 85% had satisfactory results. It is logical that the pyriformis muscle can play an important role in the production of sciatic associated with intraspinal lesions. Tension on the sciatic nerve, which passes in close approximation to the pyriformis muscle anteriorly, can be relieved by division of the pyriformis muscle."} {"id": "PMID:1275709", "title": "Inhibition of influenza RNA synthesis by virazole (ribavirin).", "content": "Virazole (ribavirin) inhibits the RNA synthesis of an influenza A virus (fowl plague). Neither virion RNA nor complementary RNA are produced. Although the effect of virazole can be counteracted by guanosine the inhibitor does not interfere with the uptake or incorporation of labelled guanosine into chick embryo cells, nor does replacement of glucose by mannose amplify the effect of virazole. Thus virazole seems not to act via an interference with the GTP pool. Synthesis of Semliki Forest virus RNA is not affected by virazole.", "contents": "Inhibition of influenza RNA synthesis by virazole (ribavirin). Virazole (ribavirin) inhibits the RNA synthesis of an influenza A virus (fowl plague). Neither virion RNA nor complementary RNA are produced. Although the effect of virazole can be counteracted by guanosine the inhibitor does not interfere with the uptake or incorporation of labelled guanosine into chick embryo cells, nor does replacement of glucose by mannose amplify the effect of virazole. Thus virazole seems not to act via an interference with the GTP pool. Synthesis of Semliki Forest virus RNA is not affected by virazole."} {"id": "PMID:1275710", "title": "[The topography of Gomori positive neurosecretory elements of the hypothalamus of the lemmings Dicrostonyx torquatus and Lemmus sibiricus].", "content": "Under study was the structure of the hypothalamo-hypophyseal neurosecretory system in two species of lemmings of the Wrangel island: the collared lemming, (Dicrostonyx torquatus) and the Ob lemming (Lemmus sibiricus). Inspite of the similarity in the general organization of this system in all rodents, certain species features were found in the topography of neurosecretory elements in the animals studied. In the Ob lemming there is a great similarity in the structures of the neurosecretory system with the albino rat than in the collared lemming. In both species of lemmings, and in the collared lemming in particular, the supraoptic nucleus is located more dorso-caudally and the paraventricular one-more dorsally. A greater amount of neurosecretory cells is found which from additional groups. The hypothalamo-hypophyseal and extrahypothalamic pathways are well pronounced. The postoptical nucleus is considerably developed. In the collared lemming it is almost equal to the supraoptic one in the amount of cells composing it. The ratio of the cells in the supraoptic and postoptic nuclei is suggested to be related to the level of the water-salt metabolism and the specific ecology of lemmings.", "contents": "[The topography of Gomori positive neurosecretory elements of the hypothalamus of the lemmings Dicrostonyx torquatus and Lemmus sibiricus]. Under study was the structure of the hypothalamo-hypophyseal neurosecretory system in two species of lemmings of the Wrangel island: the collared lemming, (Dicrostonyx torquatus) and the Ob lemming (Lemmus sibiricus). Inspite of the similarity in the general organization of this system in all rodents, certain species features were found in the topography of neurosecretory elements in the animals studied. In the Ob lemming there is a great similarity in the structures of the neurosecretory system with the albino rat than in the collared lemming. In both species of lemmings, and in the collared lemming in particular, the supraoptic nucleus is located more dorso-caudally and the paraventricular one-more dorsally. A greater amount of neurosecretory cells is found which from additional groups. The hypothalamo-hypophyseal and extrahypothalamic pathways are well pronounced. The postoptical nucleus is considerably developed. In the collared lemming it is almost equal to the supraoptic one in the amount of cells composing it. The ratio of the cells in the supraoptic and postoptic nuclei is suggested to be related to the level of the water-salt metabolism and the specific ecology of lemmings."} {"id": "PMID:1275711", "title": "[Morphometric and electron microscopic studies of the secretory granules of neurosecretory cells of the supraoptic and paraventricular nuclei of white rats and mice].", "content": "The morphometrical and electron microscopic analysis of secretory granules in the perikaryons of neurosecretory cells of the supraoptic and paraventricular nuclei in male rats and mice has shown than in the cells of these nuclei in both species of animals there occur secretory granules of the same kind and size. Therefore this method fails to determine which of them contain oxytocin and which of them contain vasorpressin. The neurosecretory granules located in the Golgi apparatus zone are of a less size and have more osmiophilic cnetral material than the granules localized on the periphery which mainly have granular central material and are of a greater size. The distinctions in the size and type of secretory granules are associated with certain stages of their \"maturation\". Granular particles appear to be \"swallen\", more active forms of storing neurohormones. The presence of larger granular particles in the supraoptic nucleus of mice allows to suggest greater reactivity of this nucleus than in rats which is likely to be associated with a higher ability of mice, as compared with rats, to adaptate to disturbances in water-salt metabolism.", "contents": "[Morphometric and electron microscopic studies of the secretory granules of neurosecretory cells of the supraoptic and paraventricular nuclei of white rats and mice]. The morphometrical and electron microscopic analysis of secretory granules in the perikaryons of neurosecretory cells of the supraoptic and paraventricular nuclei in male rats and mice has shown than in the cells of these nuclei in both species of animals there occur secretory granules of the same kind and size. Therefore this method fails to determine which of them contain oxytocin and which of them contain vasorpressin. The neurosecretory granules located in the Golgi apparatus zone are of a less size and have more osmiophilic cnetral material than the granules localized on the periphery which mainly have granular central material and are of a greater size. The distinctions in the size and type of secretory granules are associated with certain stages of their \"maturation\". Granular particles appear to be \"swallen\", more active forms of storing neurohormones. The presence of larger granular particles in the supraoptic nucleus of mice allows to suggest greater reactivity of this nucleus than in rats which is likely to be associated with a higher ability of mice, as compared with rats, to adaptate to disturbances in water-salt metabolism."} {"id": "PMID:1275712", "title": "[Severbal new problems in evolutionary histology].", "content": "The classical evolutionary histology as a most important section of theoretical morphology created by workd of A.A. Zavarzin, N.G. Khlopin and A.V. Rumiantsev needs a revision on the basis of achievements of modern morphology, first of all the experimental morphology which have accumulated a vast factual material on a repeated (regenerative, transplantational, inflammatory) morphogenesis, brought about on the basis of the constructive (plastic) activity of tissues which escaped the researchers' attention in the classical period of development of evolutionary histology. A demand to create a new system of the tissue, based on characteristics of their plastic (constructive) activity became urgent. The proposed attempt of the evolutionary classification of tissues comes from the experience of researches of the constructive (plastic) activity of tissues, with the Darwin--Severtsov rule of the dependence of every individual and phylogenetic change of the organization of its pre-existing state taken into consideration.", "contents": "[Severbal new problems in evolutionary histology]. The classical evolutionary histology as a most important section of theoretical morphology created by workd of A.A. Zavarzin, N.G. Khlopin and A.V. Rumiantsev needs a revision on the basis of achievements of modern morphology, first of all the experimental morphology which have accumulated a vast factual material on a repeated (regenerative, transplantational, inflammatory) morphogenesis, brought about on the basis of the constructive (plastic) activity of tissues which escaped the researchers' attention in the classical period of development of evolutionary histology. A demand to create a new system of the tissue, based on characteristics of their plastic (constructive) activity became urgent. The proposed attempt of the evolutionary classification of tissues comes from the experience of researches of the constructive (plastic) activity of tissues, with the Darwin--Severtsov rule of the dependence of every individual and phylogenetic change of the organization of its pre-existing state taken into consideration."} {"id": "PMID:1275713", "title": "[A brief outline of the evolution of lymphoid tissue and its immunocellular reactivity in vertebrates].", "content": "The steps of the phylogenetic development of the lymphoid tissue and its immunolcellular reactivity were studied. It was shown that a gradual change from lymphoid multifunctional cells disposed diffusely in primitive lower vertebrates to the concentration of lymphoid cells into complicatedly arranged lymph nodes was taking place. Common features and species (group) peculiarities of the structure of the lymphoid tissue and its immunological reactivity were studied. The similar succession of immunocellular reactions has the phagocyte reaction as the first link. Then goes the lymphocyte reaction with a following transformation of lymphocytes to blasts and their further differentiation and proliferation into young forms of cells of the plasmocyte row. The antibody-forming cells were found in all the vertebrates studied and their morphology was under research. Species peculiarities of lymphoid cells and their immunoreactivity were studied.", "contents": "[A brief outline of the evolution of lymphoid tissue and its immunocellular reactivity in vertebrates]. The steps of the phylogenetic development of the lymphoid tissue and its immunolcellular reactivity were studied. It was shown that a gradual change from lymphoid multifunctional cells disposed diffusely in primitive lower vertebrates to the concentration of lymphoid cells into complicatedly arranged lymph nodes was taking place. Common features and species (group) peculiarities of the structure of the lymphoid tissue and its immunological reactivity were studied. The similar succession of immunocellular reactions has the phagocyte reaction as the first link. Then goes the lymphocyte reaction with a following transformation of lymphocytes to blasts and their further differentiation and proliferation into young forms of cells of the plasmocyte row. The antibody-forming cells were found in all the vertebrates studied and their morphology was under research. Species peculiarities of lymphoid cells and their immunoreactivity were studied."} {"id": "PMID:1275714", "title": "[Comparison of the histochemical bases of epidermis differentiation in vertebrates].", "content": "It was been shown that in the line of forms of amphibia, reptiles, mammals, including man, the histochemical differentiation of the epidermis is related with changes in protective and transitory zones. For instance, in amphibia the accomodation to the terranian medium is accompanied by establishment of the vertical histochemical gradient in the epidermis which is manifested by accumulation of a protein rich in cationic and sulfhydril groups in the protective zone. The epidermis of reptiles is characterized by presence of high concentrations of a protein rich in cystine in the protective zone. The transient zone is formed on the border of the protective and germinative zones. The epidermis of mammals retains in general features the histochemical type of differentiation of the protective zone which had appeared in reptiles. However, the transient zone of the mammalian epidermis has a high concentration of proteins rich in histidine and arginin. The histochemical differentiation of the human epidermis is related with the distribution of the hairy integument.", "contents": "[Comparison of the histochemical bases of epidermis differentiation in vertebrates]. It was been shown that in the line of forms of amphibia, reptiles, mammals, including man, the histochemical differentiation of the epidermis is related with changes in protective and transitory zones. For instance, in amphibia the accomodation to the terranian medium is accompanied by establishment of the vertical histochemical gradient in the epidermis which is manifested by accumulation of a protein rich in cationic and sulfhydril groups in the protective zone. The epidermis of reptiles is characterized by presence of high concentrations of a protein rich in cystine in the protective zone. The transient zone is formed on the border of the protective and germinative zones. The epidermis of mammals retains in general features the histochemical type of differentiation of the protective zone which had appeared in reptiles. However, the transient zone of the mammalian epidermis has a high concentration of proteins rich in histidine and arginin. The histochemical differentiation of the human epidermis is related with the distribution of the hairy integument."} {"id": "PMID:1275715", "title": "[Endocrine cells of the mucous membrane of the fundus region of the stomach of hibernating rodents].", "content": "The gastric mucous membrane was studied in the hibernating animal Citellus erythrogenys in different seasons (during 7-8 months a year the animal is in hibernation and its digestive tract is not functioning). During hibernation the general amount of enterochromaffin-like cells decreases and their composition changes: the number of active cells diminishes and that of less active cells grows. Such dynamics of cells suggests the participation of enterochromaffin-like cells of Citellus erythrogenys in the regulation of gastric secretion (in rats and mice these cells contain histamine stimulating the mucous membrane glands). The amount of true enterochromaffin cells is not sufficiently changed and they seem to be not directly related with digestion but to be producers of serotonin which (together with serotonin of the brain) takes part in sustaining the mechanisms of appearance and supporting of winter hibernation.", "contents": "[Endocrine cells of the mucous membrane of the fundus region of the stomach of hibernating rodents]. The gastric mucous membrane was studied in the hibernating animal Citellus erythrogenys in different seasons (during 7-8 months a year the animal is in hibernation and its digestive tract is not functioning). During hibernation the general amount of enterochromaffin-like cells decreases and their composition changes: the number of active cells diminishes and that of less active cells grows. Such dynamics of cells suggests the participation of enterochromaffin-like cells of Citellus erythrogenys in the regulation of gastric secretion (in rats and mice these cells contain histamine stimulating the mucous membrane glands). The amount of true enterochromaffin cells is not sufficiently changed and they seem to be not directly related with digestion but to be producers of serotonin which (together with serotonin of the brain) takes part in sustaining the mechanisms of appearance and supporting of winter hibernation."} {"id": "PMID:1275716", "title": "[Anatomo-histologic findings clarifying the phylogenetic relationships between salmonoid fish (Salmonoidei)].", "content": "The comparative anatomo-histological analysis of the medial gut of Osmeridae and Plecoglossidae after Iwai (1962) has revealed a great similarity in the structure of this entosomatic organ suggesting their phylogenetically close nature. On the contrary, the fine structure of the medial gut in these two families substantially differs from the structure of this organ in Salmonoidee. Pronounced distinctions were found between the structure of the medial gut of smelts and that of the pike (Esox lucius Linn\u00e9). The complicatedly differentiated medial gut of the pike is so different from the primitive gut of modern smelts that the hypothesis (Starks, 1930; Berg, 1940) on the origin of Ecosoidei from ancient Osmeridae does not seem probable. The data obtained by the anatomo-histological analysis in combination with data of other sciences should be taken into consideration when creating the natural system of Salmonoidei, since they contribute to more exact character of their phylogenetic relations.", "contents": "[Anatomo-histologic findings clarifying the phylogenetic relationships between salmonoid fish (Salmonoidei)]. The comparative anatomo-histological analysis of the medial gut of Osmeridae and Plecoglossidae after Iwai (1962) has revealed a great similarity in the structure of this entosomatic organ suggesting their phylogenetically close nature. On the contrary, the fine structure of the medial gut in these two families substantially differs from the structure of this organ in Salmonoidee. Pronounced distinctions were found between the structure of the medial gut of smelts and that of the pike (Esox lucius Linn\u00e9). The complicatedly differentiated medial gut of the pike is so different from the primitive gut of modern smelts that the hypothesis (Starks, 1930; Berg, 1940) on the origin of Ecosoidei from ancient Osmeridae does not seem probable. The data obtained by the anatomo-histological analysis in combination with data of other sciences should be taken into consideration when creating the natural system of Salmonoidei, since they contribute to more exact character of their phylogenetic relations."} {"id": "PMID:1275717", "title": "[Ultrastructure of pigeon peripheral blood cells].", "content": "The ultrastructural organization of erythrocytes, thrombocytes and white cells (pseudoeosinophils, eosinophils, basophils, lymphocytes, monocytes) of the peripheral blood was studied in the pigeon Columba livia. The specific granules of eosinophils do not contain crystalloid structures characteristic of eosinophilic granules of certain respresentatives of fishes and mammals. Specific basophilic granules are of a large size and have homogeneous osmophilic matrix. The ultrastructure of agranulocytes (lymphocytes and monocytes) have no substantial distinctions from the similar cells of other representatives of vertebrates.", "contents": "[Ultrastructure of pigeon peripheral blood cells]. The ultrastructural organization of erythrocytes, thrombocytes and white cells (pseudoeosinophils, eosinophils, basophils, lymphocytes, monocytes) of the peripheral blood was studied in the pigeon Columba livia. The specific granules of eosinophils do not contain crystalloid structures characteristic of eosinophilic granules of certain respresentatives of fishes and mammals. Specific basophilic granules are of a large size and have homogeneous osmophilic matrix. The ultrastructure of agranulocytes (lymphocytes and monocytes) have no substantial distinctions from the similar cells of other representatives of vertebrates."} {"id": "PMID:1275718", "title": "[An experimental-morphologic study of the regenerative capacity of the nematode Pontonema vulgaris (Bastian, 1865)].", "content": "In free esea nematodas Pontonema vulgaris (Bast). end portions were cut off and internal organs were damaged without disturbing the integrity of the cuticle (at the level of the oesophagus, anterior and medial parts of the gut and at the tail level). Reparative processes were registrated under conditions of \"closed\" traumas only. Removal of degenerating cells and a closure of the wound in the gut was brought about due to the active shift of the intestinal epithelium edges towards one another. The rest of degenerating cells found themselves in the gut lumen and were gradually adsorbed by entodermal cells. A deficiency of the intestinal epithelium cells is made up due to mitotic division of these cells in the epithelium areas adjacent to the site of the trauma. Regeneration in females was found to be more rapid than in males.", "contents": "[An experimental-morphologic study of the regenerative capacity of the nematode Pontonema vulgaris (Bastian, 1865)]. In free esea nematodas Pontonema vulgaris (Bast). end portions were cut off and internal organs were damaged without disturbing the integrity of the cuticle (at the level of the oesophagus, anterior and medial parts of the gut and at the tail level). Reparative processes were registrated under conditions of \"closed\" traumas only. Removal of degenerating cells and a closure of the wound in the gut was brought about due to the active shift of the intestinal epithelium edges towards one another. The rest of degenerating cells found themselves in the gut lumen and were gradually adsorbed by entodermal cells. A deficiency of the intestinal epithelium cells is made up due to mitotic division of these cells in the epithelium areas adjacent to the site of the trauma. Regeneration in females was found to be more rapid than in males."} {"id": "PMID:1275719", "title": "[Morphodynamics of the nervous system in the regenerative processes of Convoluta convoluta (Turbellaria, Acoela)].", "content": "By means of the method for revealing cholinesterases the alterations in the nervous system of Convoluta convoluta after mechanical lesion were studied. After a transversal transection of the animal into two pieces the anterior part of the body acquired the normal form within 3-4 days; the nervous system underwent inconsiderable transformations associated with a formation of a plexus in the injured area. The posterior parts of the body regenerated slowly. During the first days disintegration of the resting parts of the nervous system was observed. Later on the diffuse cholinesterase activity suggesting the beginning of the brain formation was manifested in the wound field. Plexus strands \"grow\" in the caudal direction from the brain in parallel with its development. Within three weeks the nervous system of the animals which had restored their mouth opening, body shape and normal behaviour consists of the brain and plexus not arranged in nervous trunks. The reaction of the nervous system to the ablation of a part of the brain and to a continuous mechanical injury were studied. The data obtained show a high morphological lability of the nervous system of Convoluta convoluta, its ability to radical structural rearrangements.", "contents": "[Morphodynamics of the nervous system in the regenerative processes of Convoluta convoluta (Turbellaria, Acoela)]. By means of the method for revealing cholinesterases the alterations in the nervous system of Convoluta convoluta after mechanical lesion were studied. After a transversal transection of the animal into two pieces the anterior part of the body acquired the normal form within 3-4 days; the nervous system underwent inconsiderable transformations associated with a formation of a plexus in the injured area. The posterior parts of the body regenerated slowly. During the first days disintegration of the resting parts of the nervous system was observed. Later on the diffuse cholinesterase activity suggesting the beginning of the brain formation was manifested in the wound field. Plexus strands \"grow\" in the caudal direction from the brain in parallel with its development. Within three weeks the nervous system of the animals which had restored their mouth opening, body shape and normal behaviour consists of the brain and plexus not arranged in nervous trunks. The reaction of the nervous system to the ablation of a part of the brain and to a continuous mechanical injury were studied. The data obtained show a high morphological lability of the nervous system of Convoluta convoluta, its ability to radical structural rearrangements."} {"id": "PMID:1275720", "title": "[Vascular-nervous relationships in the valves of the heart].", "content": "Method of silver nitrate impregnation was used in order to study 50 preparations of not-changed atrioventricular valves of the heart of domestic bulls and 30 preparations of the same valves of adult humans. It has been shown that in heart valves there are certain relationships between striated muscle fibres, blood vessels and nerve elements. The nerve structures of the valves are represented by nerve bundles of different thickness. In their composition there are comparatively thin non-myelinated and thicker myelinated fibres. Towards the free edge of cusps the nerve bundles become thinner and the nerve trunks give off separate thin nerve fibres disposed along the vessels of a capillary type and in some places getting around them. In certain portions of cusps the nerve bundles, some of which have zigzag sinuosity, cross blood vessels in different directions. In man the major mass of blood vessels and nerve elements are disposed near the base of the valve cusps, accompanying the muscle fibre bundles penetrating from the base side. In the bull heart valves an amount of blood vessels and nerve elements is found in considerable portions of the cusps not connected with muscle fibres.", "contents": "[Vascular-nervous relationships in the valves of the heart]. Method of silver nitrate impregnation was used in order to study 50 preparations of not-changed atrioventricular valves of the heart of domestic bulls and 30 preparations of the same valves of adult humans. It has been shown that in heart valves there are certain relationships between striated muscle fibres, blood vessels and nerve elements. The nerve structures of the valves are represented by nerve bundles of different thickness. In their composition there are comparatively thin non-myelinated and thicker myelinated fibres. Towards the free edge of cusps the nerve bundles become thinner and the nerve trunks give off separate thin nerve fibres disposed along the vessels of a capillary type and in some places getting around them. In certain portions of cusps the nerve bundles, some of which have zigzag sinuosity, cross blood vessels in different directions. In man the major mass of blood vessels and nerve elements are disposed near the base of the valve cusps, accompanying the muscle fibre bundles penetrating from the base side. In the bull heart valves an amount of blood vessels and nerve elements is found in considerable portions of the cusps not connected with muscle fibres."} {"id": "PMID:1275723", "title": "[The segmental structure of human kidneys].", "content": "The architectonics of renal arteries and veins and the structure of the calyx-pelvis complex were studied by the method of polychromic injection of tubular systems of the kidney followed by corrosion (200 kidneys). Basing on specific features in the structure of the systems in question, 4 sectors and 4-12 segments were found. In many segments two-six subsegments can be revealed (usually 2-3). The segmentary arteries and veins are described.", "contents": "[The segmental structure of human kidneys]. The architectonics of renal arteries and veins and the structure of the calyx-pelvis complex were studied by the method of polychromic injection of tubular systems of the kidney followed by corrosion (200 kidneys). Basing on specific features in the structure of the systems in question, 4 sectors and 4-12 segments were found. In many segments two-six subsegments can be revealed (usually 2-3). The segmentary arteries and veins are described."} {"id": "PMID:1275724", "title": "[Innervation of the human internal carotid arteries under normal conditions and in stenosis].", "content": "The neurohistological investigation of a portion of the internal carotid artery removed in operation on the occasion of occlusion revealed afferent, cholinergic and adrenergic nerve elements randomly located in the examined area. The histochemical and electronmicroscopic investigation of the superior cervical sympathetic ganglion removed from 42 patient operated on the occasion of occlusion of the carotid artery revealed a depletion in the ganglia of synaptic active zones, focal absence of catecholamines and neurohistological materials suggests that a substantial role in the process of stenosing of vascular walls is played by sophisticated effects of innervation connections upon the vessel sheaths.", "contents": "[Innervation of the human internal carotid arteries under normal conditions and in stenosis]. The neurohistological investigation of a portion of the internal carotid artery removed in operation on the occasion of occlusion revealed afferent, cholinergic and adrenergic nerve elements randomly located in the examined area. The histochemical and electronmicroscopic investigation of the superior cervical sympathetic ganglion removed from 42 patient operated on the occasion of occlusion of the carotid artery revealed a depletion in the ganglia of synaptic active zones, focal absence of catecholamines and neurohistological materials suggests that a substantial role in the process of stenosing of vascular walls is played by sophisticated effects of innervation connections upon the vessel sheaths."} {"id": "PMID:1275725", "title": "[A functional-morphologic analysis of reactive changes in nerve fibers during development of collateral circulation in nerves].", "content": "After stopping the blood circulation along the femoral artery the collateral blood circulation is developing unevenly in different nerves. It depends on the architectonics of blood vessels of the zone. In time the intravenous anastomosis in the distal part of the ischiatic nerve sharply increases. It is pulsing and compressing the nerve bundles and may have a negative influence on nerve fibres. Reactive morphological changes of the axis cylinder, myelin incisions and Ranvier's constrictions are found in such a nerve. The analysis has shown that the changes noted have a character of local non-specific process accompanying physiological manifestations of parabiosis.", "contents": "[A functional-morphologic analysis of reactive changes in nerve fibers during development of collateral circulation in nerves]. After stopping the blood circulation along the femoral artery the collateral blood circulation is developing unevenly in different nerves. It depends on the architectonics of blood vessels of the zone. In time the intravenous anastomosis in the distal part of the ischiatic nerve sharply increases. It is pulsing and compressing the nerve bundles and may have a negative influence on nerve fibres. Reactive morphological changes of the axis cylinder, myelin incisions and Ranvier's constrictions are found in such a nerve. The analysis has shown that the changes noted have a character of local non-specific process accompanying physiological manifestations of parabiosis."} {"id": "PMID:1275726", "title": "[New findings on the innervation of nerves proper].", "content": "The study by the author and his co-workers of the innervation of the sheaths of extraorganic (spinal and cerebral) and intraorganic nerves has shown that their nervous apparatus is differentiated in accordance with differentiation of epi-, peri- and endoneurium. The peculiar features of the innervation of sheaths of different nerves correspond to their functions and pathoplastical individuality and manifest themselves by uneven complexity, concentration and microtopography of nerve structures in the sheaths and by distinctions in the development and reactivity. Interrelationships and correlation was established between the specific functional readiness of nerve conductors and the structural organization of their sheaths' nervous apparatus. The phenomenon of reciprocal innervation of nerves was established in experiment as well as earlier reactive and compensatory-reparative processes in the nervous apparatus of nerve sheaths as compared with their conductors.", "contents": "[New findings on the innervation of nerves proper]. The study by the author and his co-workers of the innervation of the sheaths of extraorganic (spinal and cerebral) and intraorganic nerves has shown that their nervous apparatus is differentiated in accordance with differentiation of epi-, peri- and endoneurium. The peculiar features of the innervation of sheaths of different nerves correspond to their functions and pathoplastical individuality and manifest themselves by uneven complexity, concentration and microtopography of nerve structures in the sheaths and by distinctions in the development and reactivity. Interrelationships and correlation was established between the specific functional readiness of nerve conductors and the structural organization of their sheaths' nervous apparatus. The phenomenon of reciprocal innervation of nerves was established in experiment as well as earlier reactive and compensatory-reparative processes in the nervous apparatus of nerve sheaths as compared with their conductors."} {"id": "PMID:1275727", "title": "[Changes in the microcirculatory bed of the compact substance of bones following local mechanical pressure, gravitational stress and hypokinesia].", "content": "Effects of different stimuli upon the structure of the microcirculatory bed of the compact substance of long tubular bones were studied in 89 animals (rabbits and cats). Prolonged local pressure on the bone resulted in transformations characterized by lacunar resorption of the compact substance in the site of application of the force and endosteal bone-formation on the opposite side of the same part of the bone. Hypergravitation caused a considerable transformation of the microcirculatory bed and the histoarchitectonics of the bone compact substance. Smooth and linear perivascular resorption took place around dilated vessels in osteon canals. It resulted information of resorption cavities. In addition, processes of bone formation took place. Due to effects of hypokinesia the transformation of the compact substance is of a regressive character. The fibrous structures of the bony tissue and blood vessels lose their regular orientation and acquire chaotic direction.", "contents": "[Changes in the microcirculatory bed of the compact substance of bones following local mechanical pressure, gravitational stress and hypokinesia]. Effects of different stimuli upon the structure of the microcirculatory bed of the compact substance of long tubular bones were studied in 89 animals (rabbits and cats). Prolonged local pressure on the bone resulted in transformations characterized by lacunar resorption of the compact substance in the site of application of the force and endosteal bone-formation on the opposite side of the same part of the bone. Hypergravitation caused a considerable transformation of the microcirculatory bed and the histoarchitectonics of the bone compact substance. Smooth and linear perivascular resorption took place around dilated vessels in osteon canals. It resulted information of resorption cavities. In addition, processes of bone formation took place. Due to effects of hypokinesia the transformation of the compact substance is of a regressive character. The fibrous structures of the bony tissue and blood vessels lose their regular orientation and acquire chaotic direction."} {"id": "PMID:1275728", "title": "[The system of bony canals as the basis for the angioarchitectonics of bones].", "content": "The spatial interrelationships of osteon canals were studied in corrosion preparations with the help of rastral electron microscopy. The structure of microvessels, their belonging to a definite link of the microcirculatory bed, the interaction of vessels and their position with respect to the osseous matrix were studied in bone sections impregnated with silver nitrate after V. V. Kuprijanov. Haversian canals in the compact substance of the bone are longitudinally oriented, can duplicate and form a single system of canals. The neighbouring canals of osteons might be bound by means of Volkmann's canals. The investigation of the Haversian canals in serial sections has shown that the diameter of the same canals of osteons can change at different levels, the diameter of the osteons themselves remaining unchanged. This seems to speak of uneven development of osteons in their different parts. In the Haversian canal there are one-two or occasionally three vessels having all three links of the morphocirculatory bed. The course and ramification of the vessel are identical to the shape of the osteon canal which includes them. The vessels are closely connected with the bony matrix by means of connective tissue bundles directed from the canal wall to the vessel wall. These bundles appear to serve as a peculiar anchor or amortizing apparatus and its elasticity might be a factor of a change of the shape and direction of the canal vessels in the bone development process.", "contents": "[The system of bony canals as the basis for the angioarchitectonics of bones]. The spatial interrelationships of osteon canals were studied in corrosion preparations with the help of rastral electron microscopy. The structure of microvessels, their belonging to a definite link of the microcirculatory bed, the interaction of vessels and their position with respect to the osseous matrix were studied in bone sections impregnated with silver nitrate after V. V. Kuprijanov. Haversian canals in the compact substance of the bone are longitudinally oriented, can duplicate and form a single system of canals. The neighbouring canals of osteons might be bound by means of Volkmann's canals. The investigation of the Haversian canals in serial sections has shown that the diameter of the same canals of osteons can change at different levels, the diameter of the osteons themselves remaining unchanged. This seems to speak of uneven development of osteons in their different parts. In the Haversian canal there are one-two or occasionally three vessels having all three links of the morphocirculatory bed. The course and ramification of the vessel are identical to the shape of the osteon canal which includes them. The vessels are closely connected with the bony matrix by means of connective tissue bundles directed from the canal wall to the vessel wall. These bundles appear to serve as a peculiar anchor or amortizing apparatus and its elasticity might be a factor of a change of the shape and direction of the canal vessels in the bone development process."} {"id": "PMID:1275729", "title": "[The disposition of the apices of the roots of multirooted teeth in the alveolar processes of the upper jaw].", "content": "Specific features of the disposition of root apexes of premolars and molars in the alveolar process of the upper jaw were studied in 148 skulls and 67 tooth-jaw cuts. The least thickness of the alveolar process was found to be at the level of the first premolar (10,41 +/- 0,33 mm), and the greatest--at the level of the first molar (14,075 +/- +/- 0,456 mm). Strong correlation of the alveolar process was established between the levels of the premolars and the last two molars. The distance from the apexes of cheek roots of the first molar to the bottom of the maxillary sinus is 2,05--2,92 mm, and the palatal roots -- 2,02 mm. On roentgenograms the molar roots are often projected on the sinus bottom.", "contents": "[The disposition of the apices of the roots of multirooted teeth in the alveolar processes of the upper jaw]. Specific features of the disposition of root apexes of premolars and molars in the alveolar process of the upper jaw were studied in 148 skulls and 67 tooth-jaw cuts. The least thickness of the alveolar process was found to be at the level of the first premolar (10,41 +/- 0,33 mm), and the greatest--at the level of the first molar (14,075 +/- +/- 0,456 mm). Strong correlation of the alveolar process was established between the levels of the premolars and the last two molars. The distance from the apexes of cheek roots of the first molar to the bottom of the maxillary sinus is 2,05--2,92 mm, and the palatal roots -- 2,02 mm. On roentgenograms the molar roots are often projected on the sinus bottom."} {"id": "PMID:1275730", "title": "[Experimental morphologic findings serving as a basis for use of xenogenic dura mater for plastic surgery of blood vessels].", "content": "Heterotransplants of the human dura mater were used to replace circular and lateral defects of the thoracic and abdominal aortas, carotid and iliac arteries in experiment. Operations were performed in 106 dogs. Observations of permeability of the vessels, morphological and histochemical studies were carried out at different periods after operation (from 1 day to 2 years). The xenogenous dura mater has well pronounced plastic properties--it is solid, elastic, characterized by low antigenicity. During transplantation there appear no hard inflammatory--destructive changes in reconstructed vessels and the surrounding tissues. The transplant is gradually substituted by recipients tissues characterized by high specialization. They are rich in elastic and smooth muscle fibres, have good blood supply and innervation. The dura mater is a good material for plastics of vascular wall defects.", "contents": "[Experimental morphologic findings serving as a basis for use of xenogenic dura mater for plastic surgery of blood vessels]. Heterotransplants of the human dura mater were used to replace circular and lateral defects of the thoracic and abdominal aortas, carotid and iliac arteries in experiment. Operations were performed in 106 dogs. Observations of permeability of the vessels, morphological and histochemical studies were carried out at different periods after operation (from 1 day to 2 years). The xenogenous dura mater has well pronounced plastic properties--it is solid, elastic, characterized by low antigenicity. During transplantation there appear no hard inflammatory--destructive changes in reconstructed vessels and the surrounding tissues. The transplant is gradually substituted by recipients tissues characterized by high specialization. They are rich in elastic and smooth muscle fibres, have good blood supply and innervation. The dura mater is a good material for plastics of vascular wall defects."} {"id": "PMID:1275732", "title": "[Changes in nerve structure on one side of the body following section of the inferior alveolar and sciatic nerves on the opposite side of the body in dogs].", "content": "The author describes changes of the lower alveolar and ischiadic nerves on the non-operated side after cutting such nerves on the opposite side of dogs, as well as changes in the organs innervated by them. The observed dystrophic changes in the nerve fibres on the non-operated side turn into more severe and non-reversible changes due to abnormal stimulation. Changes of masticatory organs appearing after cutting the lower alveolar nerve have bilateral manifestations being more pronounced on the same side especially in the case of a simultaneous dissection of the lower alveolar artery. These investigations contribute to possible interpretation of cases of symmetrical caries, development of dento-maxillary deformations on both sides.", "contents": "[Changes in nerve structure on one side of the body following section of the inferior alveolar and sciatic nerves on the opposite side of the body in dogs]. The author describes changes of the lower alveolar and ischiadic nerves on the non-operated side after cutting such nerves on the opposite side of dogs, as well as changes in the organs innervated by them. The observed dystrophic changes in the nerve fibres on the non-operated side turn into more severe and non-reversible changes due to abnormal stimulation. Changes of masticatory organs appearing after cutting the lower alveolar nerve have bilateral manifestations being more pronounced on the same side especially in the case of a simultaneous dissection of the lower alveolar artery. These investigations contribute to possible interpretation of cases of symmetrical caries, development of dento-maxillary deformations on both sides."} {"id": "PMID:1275733", "title": "[The effect of portal hypertension on the structure of the pancreas in rats during the early periods of the experiment].", "content": "The model of Hiari disease obtained by a 50% constriction of the rat's posterior portal vein under the diaphragm was used in order to study the response of different structures of the pancreas on the 1st, 3, 5, 7, 15th days of experiment. The arterial vessels were found to have fairly active responses to venous congestion. The greatest load in sustaining microcirculation falls to large arteries, so they are more subjected to dystrophies, the severeness of which is proportional to the thickness of the vessels walls. In later terms of the experiment smaller arterial vessels are involved. Within a month blood circulation in the organ deteriorates and there appear small hemorrhages. The venous congestion results in a change of the structure and secretion of the acinous and insular cells of the pancreas.", "contents": "[The effect of portal hypertension on the structure of the pancreas in rats during the early periods of the experiment]. The model of Hiari disease obtained by a 50% constriction of the rat's posterior portal vein under the diaphragm was used in order to study the response of different structures of the pancreas on the 1st, 3, 5, 7, 15th days of experiment. The arterial vessels were found to have fairly active responses to venous congestion. The greatest load in sustaining microcirculation falls to large arteries, so they are more subjected to dystrophies, the severeness of which is proportional to the thickness of the vessels walls. In later terms of the experiment smaller arterial vessels are involved. Within a month blood circulation in the organ deteriorates and there appear small hemorrhages. The venous congestion results in a change of the structure and secretion of the acinous and insular cells of the pancreas."} {"id": "PMID:1275734", "title": "[Duration of synostosis of the ischiopubic synchondrosis].", "content": "A table of the developmental rate of synostosing pubic-ischiatic synchondrosis is made on the basis of analysis of 305 pelvis roentgenograms of children from 2 till 14 years of age. The obtained data may be used in clinical differential diagnosing between such process and osteochondropathy of pubic-ischiatic synchondrosis as well as for determining the bone age of children", "contents": "[Duration of synostosis of the ischiopubic synchondrosis]. A table of the developmental rate of synostosing pubic-ischiatic synchondrosis is made on the basis of analysis of 305 pelvis roentgenograms of children from 2 till 14 years of age. The obtained data may be used in clinical differential diagnosing between such process and osteochondropathy of pubic-ischiatic synchondrosis as well as for determining the bone age of children"} {"id": "PMID:1275773", "title": "[Carcinoids of the rectum].", "content": "A total of 8 carcinoids of the rectum were investigated. The group of carcinoids was not uniform even when their anatomical localization was the same. Depending upon the histological structure of carcinoids two main morphological variants were singled out: cellular-alveolar and band-solid. In some part of the tumoral cells of all carcinoids there were revealed lipids, mucus, at the same time in no case argentaffine granulation was observed. Muculent stromas were characteristic of all carcinoids of this localization. Invasion of the muscular layer, their size being more than 2 cm, should be considered as a sign of malignancy of carcinoids. The presence of fat and mucus the absence of argentaffine granulation in cells of the tumour cannot be regarded as proofs of malignancy of carcinoids.", "contents": "[Carcinoids of the rectum]. A total of 8 carcinoids of the rectum were investigated. The group of carcinoids was not uniform even when their anatomical localization was the same. Depending upon the histological structure of carcinoids two main morphological variants were singled out: cellular-alveolar and band-solid. In some part of the tumoral cells of all carcinoids there were revealed lipids, mucus, at the same time in no case argentaffine granulation was observed. Muculent stromas were characteristic of all carcinoids of this localization. Invasion of the muscular layer, their size being more than 2 cm, should be considered as a sign of malignancy of carcinoids. The presence of fat and mucus the absence of argentaffine granulation in cells of the tumour cannot be regarded as proofs of malignancy of carcinoids."} {"id": "PMID:1275774", "title": "[The chief types of calcinosis of the coronary arteries of the heart].", "content": "On the basis of histological and some histochemical investigations of the coronary arteries of 150 persons who had died in the age of 10-79 year it was established that the main types of calcification of these arteries were the following: calcification of the inner elastic membrane (it can be determined only in a histological investigation); microgranular calcifications observed, as a rule, in the region of atherosclerotic plaques; laminar calcification which develops on places of necrotic areas in the fibrotically-changed intima of the arteries. Laminar calcification is responsible for the gravest forms of calcinosis. Calcification of atherosclerotic plaques, identified in macroscopic investigations of the arteries as microgranular, was closely connected with the evolution of atherosclerotic plaques and not infrequently progressed with their sclerosing. Vascularization of the changed vascular wall and the degree of its calcinosis were found as a rule to be inversely proportional.", "contents": "[The chief types of calcinosis of the coronary arteries of the heart]. On the basis of histological and some histochemical investigations of the coronary arteries of 150 persons who had died in the age of 10-79 year it was established that the main types of calcification of these arteries were the following: calcification of the inner elastic membrane (it can be determined only in a histological investigation); microgranular calcifications observed, as a rule, in the region of atherosclerotic plaques; laminar calcification which develops on places of necrotic areas in the fibrotically-changed intima of the arteries. Laminar calcification is responsible for the gravest forms of calcinosis. Calcification of atherosclerotic plaques, identified in macroscopic investigations of the arteries as microgranular, was closely connected with the evolution of atherosclerotic plaques and not infrequently progressed with their sclerosing. Vascularization of the changed vascular wall and the degree of its calcinosis were found as a rule to be inversely proportional."} {"id": "PMID:1275775", "title": "[Postmortem changes in the endothelial contour of the surface of large human arteries].", "content": "Changes in the relief of the endothelial surface of the common carotid artery common iliac artery in man in the postmortem period were studied by the method of scanning electron microscopy. It is established that the normal relief of the inner surface of the vessels could be studied only during the first few hours after death. Rapidly developing postmortem changes lead to drastic distortion of the stratified endothelial surface and to desquamation of the endothelial lining. On the 2nd and 3rd day of the postmortem period the relief of the inner surface of the vessel is determined by the elements which are incorporated into the composition of the subendothelial layer of the intima.", "contents": "[Postmortem changes in the endothelial contour of the surface of large human arteries]. Changes in the relief of the endothelial surface of the common carotid artery common iliac artery in man in the postmortem period were studied by the method of scanning electron microscopy. It is established that the normal relief of the inner surface of the vessels could be studied only during the first few hours after death. Rapidly developing postmortem changes lead to drastic distortion of the stratified endothelial surface and to desquamation of the endothelial lining. On the 2nd and 3rd day of the postmortem period the relief of the inner surface of the vessel is determined by the elements which are incorporated into the composition of the subendothelial layer of the intima."} {"id": "PMID:1275776", "title": "[Histochemical properties of the heparin-protein complex of mast cells and the state of the blood coagulating system in a primary lesion focus of non-specific ulcerative colitis].", "content": "Histochemical characteristics of polyanionic-cationic complex of mast cells, morphology of the microcirculatory bed of the large intestine, and a functional state of the coagulating blood system in the general blood flow and in the focus of primary inflammation were studied in patients with nonspecific ulcerative colitis. In the mast cells of the diseases intestine there was found a heparin-albuminous complex, saline resistance of the latter considerably exceed that in the norm. In the focus of primary inflammation deficit of active heparin and rise in coagulating characteristics of the blood were revealed. In the microcirculatory bed of the intestine angioniatosis, stasis, and thrombosis were observed. Impairment of complex-formation in the mast cells with appearance in their cytoplasm of the resistant heparin-albuminous complex apparently caused the local deficit of heparin and initiated the thrombogenesis in the microcirculatory bed. Thrombosis of the vessels led to hemorrhages, bleeding, disorder of the vascular wall feeding and its necrosis.", "contents": "[Histochemical properties of the heparin-protein complex of mast cells and the state of the blood coagulating system in a primary lesion focus of non-specific ulcerative colitis]. Histochemical characteristics of polyanionic-cationic complex of mast cells, morphology of the microcirculatory bed of the large intestine, and a functional state of the coagulating blood system in the general blood flow and in the focus of primary inflammation were studied in patients with nonspecific ulcerative colitis. In the mast cells of the diseases intestine there was found a heparin-albuminous complex, saline resistance of the latter considerably exceed that in the norm. In the focus of primary inflammation deficit of active heparin and rise in coagulating characteristics of the blood were revealed. In the microcirculatory bed of the intestine angioniatosis, stasis, and thrombosis were observed. Impairment of complex-formation in the mast cells with appearance in their cytoplasm of the resistant heparin-albuminous complex apparently caused the local deficit of heparin and initiated the thrombogenesis in the microcirculatory bed. Thrombosis of the vessels led to hemorrhages, bleeding, disorder of the vascular wall feeding and its necrosis."} {"id": "PMID:1275777", "title": "[The morphology and morphogenesis of alcoholic cirrhosis of the liver].", "content": "A total of 42 biopsy specimens of the liver (blind and spot) in 32 patients with alcoholic cirrhosis of the liver were investigated. Morphological, portal, postnecrotic, and mixed types of cirrhosis were established. The portal type of cirrhosis is most common. On the basis of repeated analyses of biopsy materials of the liver it may be assumed that the development of cirrhosis of the liver of alcoholic etiology is connected with multiple attacks of acute alcoholic hepatitis. Abstention from alcohol consumption resulted in stifestations of exacerbation of cirrhosis. On the other hand, continuation of alcohol consumption contributed to progressing of cirrhosis, which following several attacks of alcoholic hepatitis, may change its morphological type: portal cirrhosis \"transforms\" into the postnecrotic or mixed type. The data obtained clarified the role of ethanol in progressing alcoholic cirrhosis of the liver, which according to the initial mecranisms of its development in postnecrotic, since every attack of acute alcoholic hepatitis is accompanied by coagulative (fields of alcoholic hyaline, or Mallory's bodies), or by colliquative (balloon dystrophy) necrosis of hepacytes.", "contents": "[The morphology and morphogenesis of alcoholic cirrhosis of the liver]. A total of 42 biopsy specimens of the liver (blind and spot) in 32 patients with alcoholic cirrhosis of the liver were investigated. Morphological, portal, postnecrotic, and mixed types of cirrhosis were established. The portal type of cirrhosis is most common. On the basis of repeated analyses of biopsy materials of the liver it may be assumed that the development of cirrhosis of the liver of alcoholic etiology is connected with multiple attacks of acute alcoholic hepatitis. Abstention from alcohol consumption resulted in stifestations of exacerbation of cirrhosis. On the other hand, continuation of alcohol consumption contributed to progressing of cirrhosis, which following several attacks of alcoholic hepatitis, may change its morphological type: portal cirrhosis \"transforms\" into the postnecrotic or mixed type. The data obtained clarified the role of ethanol in progressing alcoholic cirrhosis of the liver, which according to the initial mecranisms of its development in postnecrotic, since every attack of acute alcoholic hepatitis is accompanied by coagulative (fields of alcoholic hyaline, or Mallory's bodies), or by colliquative (balloon dystrophy) necrosis of hepacytes."} {"id": "PMID:1275778", "title": "[Esthesioblastoma of the nose].", "content": "Morphological investigations of biopsy materials in 8 cases of esthesioblastomas of the nasal cavity were carried out. The three morphological variants of the tumour are described: esthesioneuroepithelioma, esthesioneurocytoma, and esthesioneuroblastoma. Rare occurrence of esthesioblastomas, peculiar features of their histological structure and difficulties of diagnosis in histological verification are emphasized. Lymphosarcoma is recommended to be differentiated from nondifferentiated cancer and sympathoblastoma. An important differentially-diagnostic procedure is considered to be a positive reaction to argentation (for identifying neurofibrils).", "contents": "[Esthesioblastoma of the nose]. Morphological investigations of biopsy materials in 8 cases of esthesioblastomas of the nasal cavity were carried out. The three morphological variants of the tumour are described: esthesioneuroepithelioma, esthesioneurocytoma, and esthesioneuroblastoma. Rare occurrence of esthesioblastomas, peculiar features of their histological structure and difficulties of diagnosis in histological verification are emphasized. Lymphosarcoma is recommended to be differentiated from nondifferentiated cancer and sympathoblastoma. An important differentially-diagnostic procedure is considered to be a positive reaction to argentation (for identifying neurofibrils)."} {"id": "PMID:1275779", "title": "[Pathologic anatomy and morphogenesis of the \"pagoda\" syndrome].", "content": "A rare case of congenital intestinal obstruction of hereditary nature, the so-called \"pagoda\" syndrome, is described. This syndrome consists in atresia of the initial department of the jejunum, considerable shortening of the intestine and in a peculiar deformation of the remaining part of the small intestine and its mesentery. The pattern of the blood supply of the intestine and its morphology support the suggestion that this syndrome is underlayed by agensia of the anterior knee of the middle intestine of the embryo, and its teratogenetic termination period does not exceed the first four weeks of embryogenesis.", "contents": "[Pathologic anatomy and morphogenesis of the \"pagoda\" syndrome]. A rare case of congenital intestinal obstruction of hereditary nature, the so-called \"pagoda\" syndrome, is described. This syndrome consists in atresia of the initial department of the jejunum, considerable shortening of the intestine and in a peculiar deformation of the remaining part of the small intestine and its mesentery. The pattern of the blood supply of the intestine and its morphology support the suggestion that this syndrome is underlayed by agensia of the anterior knee of the middle intestine of the embryo, and its teratogenetic termination period does not exceed the first four weeks of embryogenesis."} {"id": "PMID:1275780", "title": "[Congenital adrenocortical hyperplasia].", "content": "The authors report about 3 cases of the congenital adreno-genital syndrome in first-born children with a high weight at birth (3900, 3600, and 4200 g) who perished in early infancy. One child, who was considered to be a boy, died of septic postoperative complications; during the operation the uterus, ovaries, tubes, phenomena of pseudofemale hemaphroditis were observed. The considerably enlarged adrenals were gyral, goffered and their cortex consisted of cells of the fetal zone. Two other boys, who perished at the age of 3 1/2 and 2 1/2 months, were sick from the birth. In the clinical picture there prevailed anorexia, dehydration, regurgitation, periodic vomiting, convulsions, clonic spasms, Hyponatrema, hyperkalemia, sudden arrest of the heart, rose no suspicion in pediatricians with respect to the salt-losing form of the adreno-genital syndrome. Post-mortem examination revealed congenital hyperplasia of the adrenals, whose cortex consisted of the fetal zone cells.", "contents": "[Congenital adrenocortical hyperplasia]. The authors report about 3 cases of the congenital adreno-genital syndrome in first-born children with a high weight at birth (3900, 3600, and 4200 g) who perished in early infancy. One child, who was considered to be a boy, died of septic postoperative complications; during the operation the uterus, ovaries, tubes, phenomena of pseudofemale hemaphroditis were observed. The considerably enlarged adrenals were gyral, goffered and their cortex consisted of cells of the fetal zone. Two other boys, who perished at the age of 3 1/2 and 2 1/2 months, were sick from the birth. In the clinical picture there prevailed anorexia, dehydration, regurgitation, periodic vomiting, convulsions, clonic spasms, Hyponatrema, hyperkalemia, sudden arrest of the heart, rose no suspicion in pediatricians with respect to the salt-losing form of the adreno-genital syndrome. Post-mortem examination revealed congenital hyperplasia of the adrenals, whose cortex consisted of the fetal zone cells."} {"id": "PMID:1275781", "title": "[Classification of tumors of the blood systems--hemoblastoses].", "content": "The article presents a review of new concepts of pathogenesis of leukemia and changes in the schemic of hemopoiesis, which lead to the need to re-examine the existing classification of leukemia. In view of the fact that histogenetic independence of stromal and hemopoietic elements has been proved, there is no need any more for the generalizing term \"reticulosis\". The authors substantiate the need for differentiation between some acute an chronic leukemias and to consider them as independent nosological forms grouped according to morphological and pathogenetic characteristics and a specific treatment required. These forms, for example, include acute lymphoblast leukemia in children, among acute leukemias - hair cell leukemia, and among chronic leukemias- diseases of heavy chains. Criteria for their identification, as well as probable sources of separate forms of leukemias are described.", "contents": "[Classification of tumors of the blood systems--hemoblastoses]. The article presents a review of new concepts of pathogenesis of leukemia and changes in the schemic of hemopoiesis, which lead to the need to re-examine the existing classification of leukemia. In view of the fact that histogenetic independence of stromal and hemopoietic elements has been proved, there is no need any more for the generalizing term \"reticulosis\". The authors substantiate the need for differentiation between some acute an chronic leukemias and to consider them as independent nosological forms grouped according to morphological and pathogenetic characteristics and a specific treatment required. These forms, for example, include acute lymphoblast leukemia in children, among acute leukemias - hair cell leukemia, and among chronic leukemias- diseases of heavy chains. Criteria for their identification, as well as probable sources of separate forms of leukemias are described."} {"id": "PMID:1275782", "title": "[Cells secreting hydrogen ions into the renal tubules].", "content": "The ultrastructure of the epithelial cells of the renal tubules and of parietal cells of the stomach in intact rats was compared with that in animals with acute metabolic acidosis and animals kept on dry food. The studies were conducted on white male rats weighing 120-150 g. Acute metabolic acidosis was induced by a single intraperitoneal injection of 1 ml of a 1% solution of ammonium chloride. Pieces of the tissue for electron microscopy were fixed with OsO4 and poured with araldit and epon-812. The studies conducted revealed the ultrastructural similarity between the dark cells of the distal gyrous tubule and collecting tubes with parietal cells of the stomach. This similarity was seen from the one-type distribution of mitochondria of the smooth-walled vesicules and appearance in acidosis of intracellular and intercellular tubules. Such cells were not revealed in the proximal tubules, however, consideration of the results obtained and the literature data makes it possible to suggest that all cells of the proximal part of the nephron secret H+-ions, this being one of their functions. In the distal gyrous tubules and in the collecting tube this function is realized by specialized dark cells.", "contents": "[Cells secreting hydrogen ions into the renal tubules]. The ultrastructure of the epithelial cells of the renal tubules and of parietal cells of the stomach in intact rats was compared with that in animals with acute metabolic acidosis and animals kept on dry food. The studies were conducted on white male rats weighing 120-150 g. Acute metabolic acidosis was induced by a single intraperitoneal injection of 1 ml of a 1% solution of ammonium chloride. Pieces of the tissue for electron microscopy were fixed with OsO4 and poured with araldit and epon-812. The studies conducted revealed the ultrastructural similarity between the dark cells of the distal gyrous tubule and collecting tubes with parietal cells of the stomach. This similarity was seen from the one-type distribution of mitochondria of the smooth-walled vesicules and appearance in acidosis of intracellular and intercellular tubules. Such cells were not revealed in the proximal tubules, however, consideration of the results obtained and the literature data makes it possible to suggest that all cells of the proximal part of the nephron secret H+-ions, this being one of their functions. In the distal gyrous tubules and in the collecting tube this function is realized by specialized dark cells."} {"id": "PMID:1275783", "title": "[Epithelial tumors of the urinary bladder].", "content": "Morphological, electron-microscopy, and histochemical investigations of the normal human mucous membrane of the bladder and 450 vocus epithelial tumours of the same localization were carried out, which made it possible to work out additional criteria for determining the degree of differentiation of tumourous cells. The structural-functional features of tumourous cells observed were used as histochemical and ultrastructural markers of the degree of maturity of different transitional-cell tumours and were taken into account in the course of the development of the pathoanatomic classification of epithelial tumours of the bladder in man.", "contents": "[Epithelial tumors of the urinary bladder]. Morphological, electron-microscopy, and histochemical investigations of the normal human mucous membrane of the bladder and 450 vocus epithelial tumours of the same localization were carried out, which made it possible to work out additional criteria for determining the degree of differentiation of tumourous cells. The structural-functional features of tumourous cells observed were used as histochemical and ultrastructural markers of the degree of maturity of different transitional-cell tumours and were taken into account in the course of the development of the pathoanatomic classification of epithelial tumours of the bladder in man."} {"id": "PMID:1275784", "title": "[Morphologic changes in the kidneys of calves with respiratory mycoplasmosis].", "content": "The kidneys of 144 naturally diseased calves and those of 47 experimentally infected with Mycoplasma bovirhinis calves were investigated by histological and immunomorphological methods. The kidneys of calves with respiratory mycoplasmosis were often found to be involved in the pathological process, and at the initial stage of the disease and at its height prolifirative, membranous-prolifirative glomerulonephritis, and at later stages proliferative-fibroplastic glomerulonephritis developed. The secondary glanular kidney is a most often outcome of glomerulonephritis. The authors hold that lesions of glomerules were caused by immunopathological mechanisms.", "contents": "[Morphologic changes in the kidneys of calves with respiratory mycoplasmosis]. The kidneys of 144 naturally diseased calves and those of 47 experimentally infected with Mycoplasma bovirhinis calves were investigated by histological and immunomorphological methods. The kidneys of calves with respiratory mycoplasmosis were often found to be involved in the pathological process, and at the initial stage of the disease and at its height prolifirative, membranous-prolifirative glomerulonephritis, and at later stages proliferative-fibroplastic glomerulonephritis developed. The secondary glanular kidney is a most often outcome of glomerulonephritis. The authors hold that lesions of glomerules were caused by immunopathological mechanisms."} {"id": "PMID:1275785", "title": "[A change in the dendrite apparatus of the central nervous system under the influence of several extreme factors].", "content": "Electron-microscopy studies of the lateral dendrite processes of the pyramidal cells of the cerebral cortex hemispheres in rabbits exposed to thermal effects, total irradiation, and to combination of these two factors, were carried out. Destructive changes in the lateral dendrite processes, consisting in their smoothing, translocation of the dendrite apparatus into the dendrite trunk, desorganization of the dendrite apparatus, were noted. The above mentioned changes in the dendrites were not accompanied by any marked impairment of the axodendrite synapses, which testified to a relative stability of the axodendrite synapses in the cerebral cortex hemispheres.", "contents": "[A change in the dendrite apparatus of the central nervous system under the influence of several extreme factors]. Electron-microscopy studies of the lateral dendrite processes of the pyramidal cells of the cerebral cortex hemispheres in rabbits exposed to thermal effects, total irradiation, and to combination of these two factors, were carried out. Destructive changes in the lateral dendrite processes, consisting in their smoothing, translocation of the dendrite apparatus into the dendrite trunk, desorganization of the dendrite apparatus, were noted. The above mentioned changes in the dendrites were not accompanied by any marked impairment of the axodendrite synapses, which testified to a relative stability of the axodendrite synapses in the cerebral cortex hemispheres."} {"id": "PMID:1275786", "title": "[Intrauterine destruction of the brain by molds].", "content": "Pathohistological changes in the brain of 15 fetuses and newborns caused by intrauterine damage with mouldy fungi, identified according to their morphological characteristics as aspergillas, are described. The predominant localization of the mycotic foci was the periventricular zone of the lateral ventricles. Special attention is given to grave lesions of the brain's vessels and the ependyma of the lateral ventricles. A collation of pathomorphological data with the results of clinical examination of the mothers and children was carried out.", "contents": "[Intrauterine destruction of the brain by molds]. Pathohistological changes in the brain of 15 fetuses and newborns caused by intrauterine damage with mouldy fungi, identified according to their morphological characteristics as aspergillas, are described. The predominant localization of the mycotic foci was the periventricular zone of the lateral ventricles. Special attention is given to grave lesions of the brain's vessels and the ependyma of the lateral ventricles. A collation of pathomorphological data with the results of clinical examination of the mothers and children was carried out."} {"id": "PMID:1275787", "title": "[Mucoepidermoid tumors of the bronchi].", "content": "A total of 14 observations on mucoepidermoid tumours of the bronchi were studied. Patients were of the age of 29-75 years. Nine tumours were exophytic, 3-- endobronchial, 2--of the type \"Iceberg\". A definite interdependence was observed between the anatomic form of the tumours and histological structure thereof. All the variants of the multi-stratified structures (pseudoepidermoid, spindle-cellular, clear-cellular, and others) were characterized by the absence of cornification, and they fully comply with the notion of ateleplasia suggested by V.G. Garshin. Similarly, in mucigenesis there was not observed metaplasia, but maturation of cells in the direction natural for the respiratory epithelium. Mucigenesis could be realized in two ways: in glandular tubes or by mucification of individual cells of the pseudoepidermoid layers. In the latter case the polar differentiation of cells was absent. Mucoepidermoid tumours may develop both from mucous glands and from tegmental epithelium of the bronchi.", "contents": "[Mucoepidermoid tumors of the bronchi]. A total of 14 observations on mucoepidermoid tumours of the bronchi were studied. Patients were of the age of 29-75 years. Nine tumours were exophytic, 3-- endobronchial, 2--of the type \"Iceberg\". A definite interdependence was observed between the anatomic form of the tumours and histological structure thereof. All the variants of the multi-stratified structures (pseudoepidermoid, spindle-cellular, clear-cellular, and others) were characterized by the absence of cornification, and they fully comply with the notion of ateleplasia suggested by V.G. Garshin. Similarly, in mucigenesis there was not observed metaplasia, but maturation of cells in the direction natural for the respiratory epithelium. Mucigenesis could be realized in two ways: in glandular tubes or by mucification of individual cells of the pseudoepidermoid layers. In the latter case the polar differentiation of cells was absent. Mucoepidermoid tumours may develop both from mucous glands and from tegmental epithelium of the bronchi."} {"id": "PMID:1275788", "title": "[The structure of the mucous membrane of the human duodenum with aging].", "content": "Features of the duodenal mucosa structure in aging were studied. Investigations were carried out on the basis of aspiration biopsy materials taken from 30 elderly (60-74 years) and 9 senile persons. The duodenal mucosa in persons aged 20-26 years was studied as controls. No gastrointestinal disorders were recorded in the anamnesis of all the persons under study. It is established that with advancing age in the duodenal mucosa atrophy processes start to develop. The number of goblet cells in the crypts and on the villi decreases. The function of Paneth's cells and that of duodenal glands weakens. The epithelium still retains considerable mitotic and amitotic activities, however, possibilities for replacing the rapidly wearing out epithelium of villi in old age are limited.", "contents": "[The structure of the mucous membrane of the human duodenum with aging]. Features of the duodenal mucosa structure in aging were studied. Investigations were carried out on the basis of aspiration biopsy materials taken from 30 elderly (60-74 years) and 9 senile persons. The duodenal mucosa in persons aged 20-26 years was studied as controls. No gastrointestinal disorders were recorded in the anamnesis of all the persons under study. It is established that with advancing age in the duodenal mucosa atrophy processes start to develop. The number of goblet cells in the crypts and on the villi decreases. The function of Paneth's cells and that of duodenal glands weakens. The epithelium still retains considerable mitotic and amitotic activities, however, possibilities for replacing the rapidly wearing out epithelium of villi in old age are limited."} {"id": "PMID:1275789", "title": "[Acute renal failure in the so-called myorenal syndrome].", "content": "Post-mortem morphological studies of the kidneys from 2 patients, who due to complications occurring in the post-operative period (operation cryothalamectomy) developed the myorenal syndrome and acute renal insufficiency, were carried out. Changes were noted in all parts of the nephron, stroma and vessels of the kidneys. The most characteristic of the myorenal syndrome was accumulation of a great number of pigmental cylinders in the lower parts of the nephrom with focal delatation of the departments located above. In pathogenesis of acute renal insufficiency in the myorenal syndrome along with impairment of the renal hemodynamics a mechanical block of the tubules with decomposition products of myoglobin is also of importance.", "contents": "[Acute renal failure in the so-called myorenal syndrome]. Post-mortem morphological studies of the kidneys from 2 patients, who due to complications occurring in the post-operative period (operation cryothalamectomy) developed the myorenal syndrome and acute renal insufficiency, were carried out. Changes were noted in all parts of the nephron, stroma and vessels of the kidneys. The most characteristic of the myorenal syndrome was accumulation of a great number of pigmental cylinders in the lower parts of the nephrom with focal delatation of the departments located above. In pathogenesis of acute renal insufficiency in the myorenal syndrome along with impairment of the renal hemodynamics a mechanical block of the tubules with decomposition products of myoglobin is also of importance."} {"id": "PMID:1275790", "title": "[A microphotometric study of the kinetics of the histochemical reaction to lactate dehydrogenase].", "content": "The aim of the work--to ascertain and substantiate concentrations of the main components of the incubation medium used for identification and quantitative evaluation of the activity of lactate dehydrogenase in cryostat sections. Studies were conducted using cryostat sections of the rat's liver as thick as 5, 10, 15 mcM with concentration in the incubation medium of lactate 25--125 mM, NAD 2--12 mM, nitrobleu and tetranitrobleu tetrazoles 0.3--5 mM, and also under conditions with addition of pyruvate in concentrations from 0.3 to 100 mM. The cytospectrophotometric method was used for evaluation of kinetic parameters of the histochemical reaction. The data on the dependence of the rate of tetrazole reduction upon the concentration of substrate, cofactor, thickness of the section and the level of the end product of the pyruvate reaction in the incubation medium were obtained. The main kinetic parameters of the enzymatic reaction in liver sections--value of Michaelis' constant and the concentration of the substrate at which the maximal rate of the reaction was observed--were calculated. Recommendations for selection of an optimal composition of the incubation medium, ensuring the strictly quantitative evaluation of the activity of an enzyme in cryostate sections are suggested.", "contents": "[A microphotometric study of the kinetics of the histochemical reaction to lactate dehydrogenase]. The aim of the work--to ascertain and substantiate concentrations of the main components of the incubation medium used for identification and quantitative evaluation of the activity of lactate dehydrogenase in cryostat sections. Studies were conducted using cryostat sections of the rat's liver as thick as 5, 10, 15 mcM with concentration in the incubation medium of lactate 25--125 mM, NAD 2--12 mM, nitrobleu and tetranitrobleu tetrazoles 0.3--5 mM, and also under conditions with addition of pyruvate in concentrations from 0.3 to 100 mM. The cytospectrophotometric method was used for evaluation of kinetic parameters of the histochemical reaction. The data on the dependence of the rate of tetrazole reduction upon the concentration of substrate, cofactor, thickness of the section and the level of the end product of the pyruvate reaction in the incubation medium were obtained. The main kinetic parameters of the enzymatic reaction in liver sections--value of Michaelis' constant and the concentration of the substrate at which the maximal rate of the reaction was observed--were calculated. Recommendations for selection of an optimal composition of the incubation medium, ensuring the strictly quantitative evaluation of the activity of an enzyme in cryostate sections are suggested."} {"id": "PMID:1275791", "title": "[The gnotobiologic approach to the study of the body's non-specific resistance to infection].", "content": "A new methodological approach to the study of the organism resistance to infection with the use of experimental animals with controlled microflora (germfree and other categories of gnotobiotic animals) is considered. Characteristics of the state of natural resistance of germfree animals, revealing considerable defects of cellular and humoral protection mechanisms, are given. Findings of experimental studies into inflammation, phagocytosis and other reactions of nonspecific resistance in gnotobiotic animals, disclosing complex mechanisms of formation of these reactions under the influence of microflora, are presented. The etiological and pathogenetic role of the microbial factor in the development of infectious diseases and in the formation of mechanisms of protective reactions at various levels of integration of the organism are discussed. Conclusions concerning prospects of the gnotobiological approach in investigating the role of the microbic factor in pathology are set forth.", "contents": "[The gnotobiologic approach to the study of the body's non-specific resistance to infection]. A new methodological approach to the study of the organism resistance to infection with the use of experimental animals with controlled microflora (germfree and other categories of gnotobiotic animals) is considered. Characteristics of the state of natural resistance of germfree animals, revealing considerable defects of cellular and humoral protection mechanisms, are given. Findings of experimental studies into inflammation, phagocytosis and other reactions of nonspecific resistance in gnotobiotic animals, disclosing complex mechanisms of formation of these reactions under the influence of microflora, are presented. The etiological and pathogenetic role of the microbial factor in the development of infectious diseases and in the formation of mechanisms of protective reactions at various levels of integration of the organism are discussed. Conclusions concerning prospects of the gnotobiological approach in investigating the role of the microbic factor in pathology are set forth."} {"id": "PMID:1275792", "title": "Anterior floor meningoencephaloceles surgical treatment. Experience based on eleven cases.", "content": "The authors relate their experience in the anterior floor meningoencephaloceles surgical treatment, excised by the intracranial pathway and extradural approach. They compare their results on five cases operated according to this technique, with other six cases treated in the same Department using other surgical procedures and with those in the literature.", "contents": "Anterior floor meningoencephaloceles surgical treatment. Experience based on eleven cases. The authors relate their experience in the anterior floor meningoencephaloceles surgical treatment, excised by the intracranial pathway and extradural approach. They compare their results on five cases operated according to this technique, with other six cases treated in the same Department using other surgical procedures and with those in the literature."} {"id": "PMID:1275793", "title": "[Intracranial cerebral herniations and secondary lesions in the brain stem].", "content": "Intracranial cerebral herniations with secondary lesions in the brain stem are reported. The secondary lesions founded on the upper brain stem of 23 encephala with cerebral herniations are described. Hemorrhages in arteries were seen in all the brains. The lesions points to a mechanical etiology, the caudal displacement of the brain stem being the most important factor. Areas of ischemic infarction were found in the brain stem in all the cases; it is suggested that they were produced by factors other than the causative of the hemorrhagic lesions.", "contents": "[Intracranial cerebral herniations and secondary lesions in the brain stem]. Intracranial cerebral herniations with secondary lesions in the brain stem are reported. The secondary lesions founded on the upper brain stem of 23 encephala with cerebral herniations are described. Hemorrhages in arteries were seen in all the brains. The lesions points to a mechanical etiology, the caudal displacement of the brain stem being the most important factor. Areas of ischemic infarction were found in the brain stem in all the cases; it is suggested that they were produced by factors other than the causative of the hemorrhagic lesions."} {"id": "PMID:1275794", "title": "[Recovery of voluntary motion in the upper extremity following hemiplegia in patients with cerebrovascular accident. Prognostic evaluation].", "content": "The study aims the registration and anlaysis of the main facts which occur during recovery of the voluntary movements in the upper extremity, in patients with hemiplegia following cerebrovascular accident, and it also intends to evaluate the prognosis. Of particular interest was the comparative recognition of the spontaneous recovery of voluntary motricity in different segments of the upper extremity in 88 patients, not previously selected, with hemiplegia after cerebrovascular accident, admitted to the hospital at the acute stage. Of the 88 hemiplegic patients studied whose further evolution has been fairly followed 56 cases (group 1) experienced clinical improvement, either with partial or total remission of neurological manifestations and complete recovery of all voluntary movements in the different upper extremity joints, while 32 patients (group 2) with persistent neurological symptoms, particularly spasticity, showed a slighter clinical improvement, as well as only partial recovery of upper extremity movements. The clinical quantification of neurological signs applied in this study, has made possible to report the main significant changes developed during the 88 patients recovery. This criteria has allowed to emphasize the degree of the spontaneous remission of symptoms and the determination of the critical level of stabilization \"plateau\". The analysis of the data supplied by the two groups led to the following conclusions: a) the critical level of remission of symptoms and the spontaneous recovery of voluntary movements ocurred around the 70th day after the installation of hemiplegia; b) the 256 average score acquired 70 days after the onset of the hemiplegia represents the critical level stabilization (plateau); c) although the presence of early initial movements, immediately after the installation of hemiplegia, is a valuable data for the prognosis, the characterization of early movement patterns is of most important meaning; d) patients with hemiplegia after cerebrovascular acident who present the thumb flexion-extension and opposition movements showed a better prognosis than those whose initial movements were represented by the elbow flexion and/or arm flexion-adduction.", "contents": "[Recovery of voluntary motion in the upper extremity following hemiplegia in patients with cerebrovascular accident. Prognostic evaluation]. The study aims the registration and anlaysis of the main facts which occur during recovery of the voluntary movements in the upper extremity, in patients with hemiplegia following cerebrovascular accident, and it also intends to evaluate the prognosis. Of particular interest was the comparative recognition of the spontaneous recovery of voluntary motricity in different segments of the upper extremity in 88 patients, not previously selected, with hemiplegia after cerebrovascular accident, admitted to the hospital at the acute stage. Of the 88 hemiplegic patients studied whose further evolution has been fairly followed 56 cases (group 1) experienced clinical improvement, either with partial or total remission of neurological manifestations and complete recovery of all voluntary movements in the different upper extremity joints, while 32 patients (group 2) with persistent neurological symptoms, particularly spasticity, showed a slighter clinical improvement, as well as only partial recovery of upper extremity movements. The clinical quantification of neurological signs applied in this study, has made possible to report the main significant changes developed during the 88 patients recovery. This criteria has allowed to emphasize the degree of the spontaneous remission of symptoms and the determination of the critical level of stabilization \"plateau\". The analysis of the data supplied by the two groups led to the following conclusions: a) the critical level of remission of symptoms and the spontaneous recovery of voluntary movements ocurred around the 70th day after the installation of hemiplegia; b) the 256 average score acquired 70 days after the onset of the hemiplegia represents the critical level stabilization (plateau); c) although the presence of early initial movements, immediately after the installation of hemiplegia, is a valuable data for the prognosis, the characterization of early movement patterns is of most important meaning; d) patients with hemiplegia after cerebrovascular acident who present the thumb flexion-extension and opposition movements showed a better prognosis than those whose initial movements were represented by the elbow flexion and/or arm flexion-adduction."} {"id": "PMID:1275795", "title": "[Chronic depression and temporal lobe dysrhythmia].", "content": "Making a bibliographic review about epileptic depression, the Author found that ictal, pre, post-ictal and inter-ictal forms are described. The last one, named by Grecu and Kalman \"Episodic temporal depression\", is accepted as lasting for hours, days or weeks. The present work analyses two patients with episodic depression, one with permanent (3 years) and later episodic form and another with permanent depression only (13 years). The comparative study of the 4 patients, the EEG results and the effect of antiepileptic treatment permise to conclude that even the episodic and the permanent depression were of epileptic etiology, with temporal lobe localisation. Based on the symptomatology found in the 4 patients, the Author admits the hypothesis that the epileptic depression is characteristic and that it should be possible to distinguish it, clinically, from other depressions. It is suggested, for this permanent form, the name \"permanent temporal depression\".", "contents": "[Chronic depression and temporal lobe dysrhythmia]. Making a bibliographic review about epileptic depression, the Author found that ictal, pre, post-ictal and inter-ictal forms are described. The last one, named by Grecu and Kalman \"Episodic temporal depression\", is accepted as lasting for hours, days or weeks. The present work analyses two patients with episodic depression, one with permanent (3 years) and later episodic form and another with permanent depression only (13 years). The comparative study of the 4 patients, the EEG results and the effect of antiepileptic treatment permise to conclude that even the episodic and the permanent depression were of epileptic etiology, with temporal lobe localisation. Based on the symptomatology found in the 4 patients, the Author admits the hypothesis that the epileptic depression is characteristic and that it should be possible to distinguish it, clinically, from other depressions. It is suggested, for this permanent form, the name \"permanent temporal depression\"."} {"id": "PMID:1275796", "title": "[Intermittent claudication by the narrowing of the spinal canal].", "content": "The cases of four patients with intermittent claudication due to compression of the cauda equina are reported. The cause of this syndrome is considered to be a compression of the cauda equina by a thickening of the ligamentum flavum. The clinical, neuro-radiological and surgical characteristics are discussed.", "contents": "[Intermittent claudication by the narrowing of the spinal canal]. The cases of four patients with intermittent claudication due to compression of the cauda equina are reported. The cause of this syndrome is considered to be a compression of the cauda equina by a thickening of the ligamentum flavum. The clinical, neuro-radiological and surgical characteristics are discussed."} {"id": "PMID:1275797", "title": "[Leber's disease. Genetic study of a family].", "content": "In this paper it is done the genetic study of a large family that segregates the hereditary optical atrophy gene. The modality of the hereditary transmission is the sex-linked recessive form (Leber's form). Five generations were studied, with a total of 134 individuals. Thirteen are affected (12 men: 1 woman). The study of the heredogram allows the observation of the high occurrence of women carriers and the affected men with descendents (2 married men in the heredogram) exhibit normal offspring (22 individuals, being 16 men and 6 women). One affected woman carrier is also observed. Such observations are in accordance with the literature. This study allows one to conclude by the high importance of genetic counselling, considering that the normal women carriers, which occur in great number, segregate the gene to individuals who will manifest the atrophy.", "contents": "[Leber's disease. Genetic study of a family]. In this paper it is done the genetic study of a large family that segregates the hereditary optical atrophy gene. The modality of the hereditary transmission is the sex-linked recessive form (Leber's form). Five generations were studied, with a total of 134 individuals. Thirteen are affected (12 men: 1 woman). The study of the heredogram allows the observation of the high occurrence of women carriers and the affected men with descendents (2 married men in the heredogram) exhibit normal offspring (22 individuals, being 16 men and 6 women). One affected woman carrier is also observed. Such observations are in accordance with the literature. This study allows one to conclude by the high importance of genetic counselling, considering that the normal women carriers, which occur in great number, segregate the gene to individuals who will manifest the atrophy."} {"id": "PMID:1275798", "title": "[Mental deficiency and malformations in a child with 5/13 chromosome translocation].", "content": "An unusual case of mental retardation and physical malformations with chromosome abnormalities in a 9 year old boy is reported. Chromosomal analysis showed either breakage and delation from some gens to 5p and/or 13q; genic mutation or, perhaps, efect of position in re-adjusted chromosomic segments.", "contents": "[Mental deficiency and malformations in a child with 5/13 chromosome translocation]. An unusual case of mental retardation and physical malformations with chromosome abnormalities in a 9 year old boy is reported. Chromosomal analysis showed either breakage and delation from some gens to 5p and/or 13q; genic mutation or, perhaps, efect of position in re-adjusted chromosomic segments."} {"id": "PMID:1275799", "title": "Total hearing rehabilitation.", "content": "The history and development of the hearing and dispensing system in this country is outlined in relation to the status of dispensing today. We enumerate the problems within the traditional system, various attempts to correct them, and advantages of variations of the traditional system. This article presents a concept of total hearing rehabilitation, including the direct dispensing of aids based on the professional otolaryngological-audiological team working together within the clinic setting. Based on the results of 20-months' experience in dispensing, we advocate a reexamination of professional roles involved in provision for hearing aids.", "contents": "Total hearing rehabilitation. The history and development of the hearing and dispensing system in this country is outlined in relation to the status of dispensing today. We enumerate the problems within the traditional system, various attempts to correct them, and advantages of variations of the traditional system. This article presents a concept of total hearing rehabilitation, including the direct dispensing of aids based on the professional otolaryngological-audiological team working together within the clinic setting. Based on the results of 20-months' experience in dispensing, we advocate a reexamination of professional roles involved in provision for hearing aids."} {"id": "PMID:1275800", "title": "Tympanic neurectomy for parotid fistula.", "content": "Complete excision of the trophic secretomotor parasympathetic nerve supply of the parotid gland produces abolition of its salivary secretion and ends in atrophy of the gland units. We report 20 patients treated by tympanic neurectomy to relieve the distressing problem of parotid fistulas. The tympanic nerve was identified and excised at its appearance through the hypotympanic floor. In seven of our cases, we found an early division of the main nerve that crossed the promontory anteriorly-hence, the importance of excising the tympanic nerve as proximal as possible. All patients observed for more than two years had complete dryness and cure of their fistulas. We describe the basis of tympanic neurectomy and its results compared with other forms of treatment.", "contents": "Tympanic neurectomy for parotid fistula. Complete excision of the trophic secretomotor parasympathetic nerve supply of the parotid gland produces abolition of its salivary secretion and ends in atrophy of the gland units. We report 20 patients treated by tympanic neurectomy to relieve the distressing problem of parotid fistulas. The tympanic nerve was identified and excised at its appearance through the hypotympanic floor. In seven of our cases, we found an early division of the main nerve that crossed the promontory anteriorly-hence, the importance of excising the tympanic nerve as proximal as possible. All patients observed for more than two years had complete dryness and cure of their fistulas. We describe the basis of tympanic neurectomy and its results compared with other forms of treatment."} {"id": "PMID:1275801", "title": "Functional eustachian tuboplasty: a new surgical technique.", "content": "Until recently, there was no answer for the \"physiologic\" stenosis of the Eustachian tube (occurring in 20% of all cases of tubal occlusion). We describe a newly devised surgical procedure-tensor palati tendon \"strengthening\"-for the management of physiologic stenosis of the Eustachian tube. After the initial dissection of 20 cadavers, the basic surgical procedure was worked out. Then, the experimental study was conducted in four dogs to evaluate the effects of this new operation on the Eustachian tube functions as well as on the soft palate movements. Finally, four patients with physiologic tubal stenosis were treated successfully. The follow-up period ranged from 16 to 20 months. Strict selection of patients is encouraged.", "contents": "Functional eustachian tuboplasty: a new surgical technique. Until recently, there was no answer for the \"physiologic\" stenosis of the Eustachian tube (occurring in 20% of all cases of tubal occlusion). We describe a newly devised surgical procedure-tensor palati tendon \"strengthening\"-for the management of physiologic stenosis of the Eustachian tube. After the initial dissection of 20 cadavers, the basic surgical procedure was worked out. Then, the experimental study was conducted in four dogs to evaluate the effects of this new operation on the Eustachian tube functions as well as on the soft palate movements. Finally, four patients with physiologic tubal stenosis were treated successfully. The follow-up period ranged from 16 to 20 months. Strict selection of patients is encouraged."} {"id": "PMID:1275802", "title": "The air caloric test. A parametric study.", "content": "We studied the normal air caloric response's intensity and variability. Intensities of \"preliminary standard\" (47 C, 25 C, 60 seconds, 10 liters/min) air and standard bithermal water responses were the same, but the air responses were more variable. Control experiments suggested that the tendency of the air stream to equilibrate toward ambient may account for much of air's relatively high variability. Increasing the air irrigation's duration, flow rate, and separation from body temperature increased response intensity. Air's test-retest variability decreased when flow rate and duration increased and when temperature approached ambient. Therefore, we suggested that irrigating temperatures be chosen as close to ambient as possible and duration and flow rate be made as large as possible. From a table equating air and standard bithermal water responses, we selected tentative clinical air irrigation parameters of 27.5 C, 45.5 C, 100 seconds, and 13 liters/min.", "contents": "The air caloric test. A parametric study. We studied the normal air caloric response's intensity and variability. Intensities of \"preliminary standard\" (47 C, 25 C, 60 seconds, 10 liters/min) air and standard bithermal water responses were the same, but the air responses were more variable. Control experiments suggested that the tendency of the air stream to equilibrate toward ambient may account for much of air's relatively high variability. Increasing the air irrigation's duration, flow rate, and separation from body temperature increased response intensity. Air's test-retest variability decreased when flow rate and duration increased and when temperature approached ambient. Therefore, we suggested that irrigating temperatures be chosen as close to ambient as possible and duration and flow rate be made as large as possible. From a table equating air and standard bithermal water responses, we selected tentative clinical air irrigation parameters of 27.5 C, 45.5 C, 100 seconds, and 13 liters/min."} {"id": "PMID:1275803", "title": "Primary squamous cell carcinoma of the parotid gland.", "content": "Primary squamous cell carcinoma of the parotid gland occurs infrequently. A retrospective study at the University of Michigan indicates an incidence of 0.3% for all parotid tumors during a 25-year period. This conforms to the data presented by other large series. Before a diagnosis of primary squamous cell carcinoma can be made, mucoepidermoid carcinomas and metastic squamous cell carcinomas must be excluded.", "contents": "Primary squamous cell carcinoma of the parotid gland. Primary squamous cell carcinoma of the parotid gland occurs infrequently. A retrospective study at the University of Michigan indicates an incidence of 0.3% for all parotid tumors during a 25-year period. This conforms to the data presented by other large series. Before a diagnosis of primary squamous cell carcinoma can be made, mucoepidermoid carcinomas and metastic squamous cell carcinomas must be excluded."} {"id": "PMID:1275804", "title": "Collapsing ears and acoustic reflex measurement with circumaural ear cushions.", "content": "Ears that collapse from audiometer ear cushion pressure may show elevated stapedial reflex thresholds. In such cases, erroneous judgments about the status of a patient's hearing are possible. Experiments on 15 normal ears suggest that the use of a circumaural ear cushion on the impedance audiometer headset is an effective method of eliminating outer ear closure and the resulting spurious thresholds, when the proper correction values by frequency are applied to the audiometer dial reading. In this study, correction values for reflex-eliciting stimuli are established and their use in a child with collapsing ears is reported.", "contents": "Collapsing ears and acoustic reflex measurement with circumaural ear cushions. Ears that collapse from audiometer ear cushion pressure may show elevated stapedial reflex thresholds. In such cases, erroneous judgments about the status of a patient's hearing are possible. Experiments on 15 normal ears suggest that the use of a circumaural ear cushion on the impedance audiometer headset is an effective method of eliminating outer ear closure and the resulting spurious thresholds, when the proper correction values by frequency are applied to the audiometer dial reading. In this study, correction values for reflex-eliciting stimuli are established and their use in a child with collapsing ears is reported."} {"id": "PMID:1275805", "title": "Dilator naris function: a useful test of facial nerve integrity.", "content": "The dilator naris muscle is an active participant of respiration in man. Its level of function appears to vary directly with ventilatory resistance. Three cases are reported to illustrate the use of the respiratory function of this muscle as a clinical test of seventh nerve integrity when its volitional function cannot be elicited.", "contents": "Dilator naris function: a useful test of facial nerve integrity. The dilator naris muscle is an active participant of respiration in man. Its level of function appears to vary directly with ventilatory resistance. Three cases are reported to illustrate the use of the respiratory function of this muscle as a clinical test of seventh nerve integrity when its volitional function cannot be elicited."} {"id": "PMID:1275806", "title": "M\u00e9ni\u00e8re disease and cerebral impairment.", "content": "A recent series of findings based on psychological test patterns suggests that the behavioral disturbance seen in M\u00e9ni\u00e8re disease is, in many instances, predicated on organic cerebral impairment. If this proves to be the case, an important source would have been uncovered that could account for some of the behavioral difficulties associated with M\u00e9ni\u00e8re disease. The present study challenges the previous reports, suggesting that these findings emerged because of imprecise methodologic procedures. The results based on our psychological test patterns reject prior conclusions that there is demonstrable evidence for organic cerebral impairment in patients with M\u00e9ni\u00e8re disease.", "contents": "M\u00e9ni\u00e8re disease and cerebral impairment. A recent series of findings based on psychological test patterns suggests that the behavioral disturbance seen in M\u00e9ni\u00e8re disease is, in many instances, predicated on organic cerebral impairment. If this proves to be the case, an important source would have been uncovered that could account for some of the behavioral difficulties associated with M\u00e9ni\u00e8re disease. The present study challenges the previous reports, suggesting that these findings emerged because of imprecise methodologic procedures. The results based on our psychological test patterns reject prior conclusions that there is demonstrable evidence for organic cerebral impairment in patients with M\u00e9ni\u00e8re disease."} {"id": "PMID:1275807", "title": "Maggot therapy for subacute mastoiditis.", "content": "We describe a patient with intractable subacute mastoiditis who was treated successfully by maggot therapy. Maggot debridement of intractable wounds was very successful before the introduction of antibiotics. We describe the indications for use, materials and methods for the rearing of sterile larvae, the modes of action, and the complications of maggot debridement.", "contents": "Maggot therapy for subacute mastoiditis. We describe a patient with intractable subacute mastoiditis who was treated successfully by maggot therapy. Maggot debridement of intractable wounds was very successful before the introduction of antibiotics. We describe the indications for use, materials and methods for the rearing of sterile larvae, the modes of action, and the complications of maggot debridement."} {"id": "PMID:1275814", "title": "Masking level differences encountered in clinical populations.", "content": "Methods for measuring masking level differences (MLDs) at 500 Hz and for spondees were used with 290 subjects: 50 persons with normal hearing and 240 patients with various diseases. Of particular interest was whether techniques currently in clinical use could be used with ease, dispatch, and profit in determining MLD size. The methods selected, which were variations of B\u00e9k\u00e9sy audiometry and speech reception threshold procedures, proved clinically feasible. Results revealed differences in behavior from one group of subjects to another. Although MLDs were not affected by cortical lesions, they were very often abnormally small for patients with eight-nerve tumor, Meni\u00e9re's disease, or multiple sclerosis. The high incidence of abnormally small MLDs in populations with normal sensitivity to pure tones and speech but with evidence of subcortical central lesions, such as patients with multiple sclerosis, suggests that the MLD tasks can be of diagnostic value in detecting retrocochlear lesions. However, in persons with hearing loss or significant interaural differences in threshold sensitivity, or both, the MLD tests are not always reliable in differentiating cochlear from retrocochlear disease.", "contents": "Masking level differences encountered in clinical populations. Methods for measuring masking level differences (MLDs) at 500 Hz and for spondees were used with 290 subjects: 50 persons with normal hearing and 240 patients with various diseases. Of particular interest was whether techniques currently in clinical use could be used with ease, dispatch, and profit in determining MLD size. The methods selected, which were variations of B\u00e9k\u00e9sy audiometry and speech reception threshold procedures, proved clinically feasible. Results revealed differences in behavior from one group of subjects to another. Although MLDs were not affected by cortical lesions, they were very often abnormally small for patients with eight-nerve tumor, Meni\u00e9re's disease, or multiple sclerosis. The high incidence of abnormally small MLDs in populations with normal sensitivity to pure tones and speech but with evidence of subcortical central lesions, such as patients with multiple sclerosis, suggests that the MLD tasks can be of diagnostic value in detecting retrocochlear lesions. However, in persons with hearing loss or significant interaural differences in threshold sensitivity, or both, the MLD tests are not always reliable in differentiating cochlear from retrocochlear disease."} {"id": "PMID:1275815", "title": "Studies in infant behavioural audiometry. II. Six-week-old infants.", "content": "The behaviour of 90 clinically normal 6-week-old babies previously studied as neonates was video-recorded while they were presented with sequences of sound stimuli. The stimuli varied in sound pressure level, bandwidth and rise time, and included two voice signals and a no-sound (control) trial. Video records were made both for the whole body aspect and for a 3 1/2 X 'close-up' of the head. Later, the video records were shown to 6 observers who were allowed to see the babies for 10 s at each trial. The first 5 s was a prestimulus observation period, and the second 5 s usually contained a sound stimulus. Between the trials, the observers were given 20 s in which to record (i) prestimulus activity, (ii) confidence in response, and (iii) movement details (data for [iii] not reported here). Different segments of the baby's body were observed on different occasions as detailed in our neonatal report. The response confidence ratings were analysed, using aspects of signal detection theory, to show differences amongst various body segments (p less than 0.001), sound pressure levels (SPL) (p less than 0.001), band widths (BW) (p less than 0.001), and rise times (RT) (p less than 0.001). There were significant interactions between SPL and BW (p less than 0.05) and SPL X RT (p less than 0.001). The 3 factor interaction (SPL X BW X RT) was also significant (p less than 0.001). A 90-dB broad-spectrum noise band was by far the most effective stimulus. The response to different sound stimuli was affected by the baby's posture (lying or sitting) and by prestimulus activity state. The results are discussed in relation to our previous neonatal study.", "contents": "Studies in infant behavioural audiometry. II. Six-week-old infants. The behaviour of 90 clinically normal 6-week-old babies previously studied as neonates was video-recorded while they were presented with sequences of sound stimuli. The stimuli varied in sound pressure level, bandwidth and rise time, and included two voice signals and a no-sound (control) trial. Video records were made both for the whole body aspect and for a 3 1/2 X 'close-up' of the head. Later, the video records were shown to 6 observers who were allowed to see the babies for 10 s at each trial. The first 5 s was a prestimulus observation period, and the second 5 s usually contained a sound stimulus. Between the trials, the observers were given 20 s in which to record (i) prestimulus activity, (ii) confidence in response, and (iii) movement details (data for [iii] not reported here). Different segments of the baby's body were observed on different occasions as detailed in our neonatal report. The response confidence ratings were analysed, using aspects of signal detection theory, to show differences amongst various body segments (p less than 0.001), sound pressure levels (SPL) (p less than 0.001), band widths (BW) (p less than 0.001), and rise times (RT) (p less than 0.001). There were significant interactions between SPL and BW (p less than 0.05) and SPL X RT (p less than 0.001). The 3 factor interaction (SPL X BW X RT) was also significant (p less than 0.001). A 90-dB broad-spectrum noise band was by far the most effective stimulus. The response to different sound stimuli was affected by the baby's posture (lying or sitting) and by prestimulus activity state. The results are discussed in relation to our previous neonatal study."} {"id": "PMID:1275816", "title": "Children's perception of temporally distorted sentential approximations of varying length.", "content": "The purpose of this study was to investigate the abilities of second-grade and fourth-grade children to auditorially process three orders of three- and five-word sentential approximations, which had normal interstimulus intervals (ISI) and ISIs of 200 and 400 ms. Results showed that percent correct scores decreased as a function of increasing sentence length and ISI, and decreasing order of sentential approximation and grade level. The results are discussed relative to theoretical notions of short-term memory and auditory perceptual processing as well as potential clinical applications.", "contents": "Children's perception of temporally distorted sentential approximations of varying length. The purpose of this study was to investigate the abilities of second-grade and fourth-grade children to auditorially process three orders of three- and five-word sentential approximations, which had normal interstimulus intervals (ISI) and ISIs of 200 and 400 ms. Results showed that percent correct scores decreased as a function of increasing sentence length and ISI, and decreasing order of sentential approximation and grade level. The results are discussed relative to theoretical notions of short-term memory and auditory perceptual processing as well as potential clinical applications."} {"id": "PMID:1275820", "title": "Lower body negative pressure: the second manned Skylab mission.", "content": "Results of orthostatic evaluations of the crew of Skylab 3 with lower body negative pressure (LNBP) stress tests during their 59-d mission are reported. The test protocol was identical to that used in the first manned Skylab mission and the latter Apollo flights. Except for an inflight increase (rather than a decrease) in resting heart rates, results were essentially parallel to those observed in crewmen of the shorter Skylab 2 mission. Exaggerated elevations in heart rate and decreases in pulse pressure during LBNP stress inflight and immediately postflight corresponded to lowered orthostatic tolerance. Large decrements in resting calf size inflight and in total leg volume postflight indicated significant headward fluid shifts as had already been seen in the Skylab 2 crewmen. In addition, decreases in calf circumference gave no certain indication of a plateau over the 59 d inflight. On the other hand, percentage volume increase in calf size during LBNP stress inflight was greater than those in either preflight or postflight tests. Hypotheses elaborated after the Skylab 2 mission seem to have been substantiated, but several enigmas await data from the last and longer mission for clarification.", "contents": "Lower body negative pressure: the second manned Skylab mission. Results of orthostatic evaluations of the crew of Skylab 3 with lower body negative pressure (LNBP) stress tests during their 59-d mission are reported. The test protocol was identical to that used in the first manned Skylab mission and the latter Apollo flights. Except for an inflight increase (rather than a decrease) in resting heart rates, results were essentially parallel to those observed in crewmen of the shorter Skylab 2 mission. Exaggerated elevations in heart rate and decreases in pulse pressure during LBNP stress inflight and immediately postflight corresponded to lowered orthostatic tolerance. Large decrements in resting calf size inflight and in total leg volume postflight indicated significant headward fluid shifts as had already been seen in the Skylab 2 crewmen. In addition, decreases in calf circumference gave no certain indication of a plateau over the 59 d inflight. On the other hand, percentage volume increase in calf size during LBNP stress inflight was greater than those in either preflight or postflight tests. Hypotheses elaborated after the Skylab 2 mission seem to have been substantiated, but several enigmas await data from the last and longer mission for clarification."} {"id": "PMID:1275817", "title": "Intelligibility of distorted speech sounds shifted in frequency and time in normal children.", "content": "Distorted speech sounds were presented to normal children aged 4-11 years and to young adults in such a way that 20 monosyllables were distorted with a 'speech stretcher' which produced frequency expansion and compression and also time expansion and compression. The experiment was performed to observe the intelligibility of such distorted speech sounds and the development of the discrimination ability in normal children. The results were as follows: (1) discrimination decreased sharply with increasing frequency change in both frequency-expanded and frequency-compressed speech; (2) discrimination was relatively unaffected by time expansion. However, with time compression there was a gradual decrease in discrimination at 50% time compression followed by a rapid deterioration at 75% time compression; (3) for a given percentage of distortion, frequency shift degraded intelligibility of speech sounds more severely than time shift, and (4) discrimination ability clearly increased with age in normal children. There was no significant difference between boys and girls.", "contents": "Intelligibility of distorted speech sounds shifted in frequency and time in normal children. Distorted speech sounds were presented to normal children aged 4-11 years and to young adults in such a way that 20 monosyllables were distorted with a 'speech stretcher' which produced frequency expansion and compression and also time expansion and compression. The experiment was performed to observe the intelligibility of such distorted speech sounds and the development of the discrimination ability in normal children. The results were as follows: (1) discrimination decreased sharply with increasing frequency change in both frequency-expanded and frequency-compressed speech; (2) discrimination was relatively unaffected by time expansion. However, with time compression there was a gradual decrease in discrimination at 50% time compression followed by a rapid deterioration at 75% time compression; (3) for a given percentage of distortion, frequency shift degraded intelligibility of speech sounds more severely than time shift, and (4) discrimination ability clearly increased with age in normal children. There was no significant difference between boys and girls."} {"id": "PMID:1275821", "title": "Quantitative electrocardiography during extended space flight: the second manned Skylab mission.", "content": "To assess the effects of space flight on cardiac electrical properties, vectorcardiograms (VCG) were obtained on the Skylab crew at regular intervals during the 59-d flight (SL3) and during the pre- and postflight periods. The Frank lead system was used and observations were made at rest; during 25%, 50%, and 75% of maximum exercise; during a short pulse of exercise (150 W, 2 min); and after exercise. Data from 47 in-flight tests were analyzed by computer and compared to preflight and postflight values. A statistically significant increase in QRS maximum vector magnitude (all SL3 crewman); and an increase in resting PR interval (all SL3 crewmen) occurred. During exercise, the PR interval did not differ from preflight. Exercise heart rates in flight were same as preflight, but increased in the immediate postflight period. No major changes in QRS, T, or ST vector direction occurred. The scientist pilot had premature ventricular beats sporadically during the flight. This astronaut also had intermittent periods of atrioventricular junctional rhythm throughout the flight. The increase in QRS maximum vector magnitude resembles the electrocardiographic changes associated with athletic conditioning and may be related to increased ventricular volume secondary to centripetal shifts of fluid and/or the in-flight isotonic exercise program. Prolongation of the PR interval at rest with normalization of exercise suggests that there was increased vagal tone or suppressed sympathetic influence during the flight.", "contents": "Quantitative electrocardiography during extended space flight: the second manned Skylab mission. To assess the effects of space flight on cardiac electrical properties, vectorcardiograms (VCG) were obtained on the Skylab crew at regular intervals during the 59-d flight (SL3) and during the pre- and postflight periods. The Frank lead system was used and observations were made at rest; during 25%, 50%, and 75% of maximum exercise; during a short pulse of exercise (150 W, 2 min); and after exercise. Data from 47 in-flight tests were analyzed by computer and compared to preflight and postflight values. A statistically significant increase in QRS maximum vector magnitude (all SL3 crewman); and an increase in resting PR interval (all SL3 crewmen) occurred. During exercise, the PR interval did not differ from preflight. Exercise heart rates in flight were same as preflight, but increased in the immediate postflight period. No major changes in QRS, T, or ST vector direction occurred. The scientist pilot had premature ventricular beats sporadically during the flight. This astronaut also had intermittent periods of atrioventricular junctional rhythm throughout the flight. The increase in QRS maximum vector magnitude resembles the electrocardiographic changes associated with athletic conditioning and may be related to increased ventricular volume secondary to centripetal shifts of fluid and/or the in-flight isotonic exercise program. Prolongation of the PR interval at rest with normalization of exercise suggests that there was increased vagal tone or suppressed sympathetic influence during the flight."} {"id": "PMID:1275818", "title": "Most comfortable listening level presentation versus maximum discrimination for word discrimination material.", "content": "The purpose of the present study was to determine if most comfortable listening level (MCL) presentation of word discrimination material would yield maximum discrimination for normal and sensorineural hearing loss subjects. The results of the study indicated that normally hearing listeners do obtain maximum discrimination at MCL, while presentation of word discrimination material at MCL to sensorineural hearing loss listeners does not yield maximum discrimination. Further examination of the results would also contraindicate the use of any other method which incorporates single or dual presentation levels as a means of determining maximum discrimination for the sensorineural hearing loss listener.", "contents": "Most comfortable listening level presentation versus maximum discrimination for word discrimination material. The purpose of the present study was to determine if most comfortable listening level (MCL) presentation of word discrimination material would yield maximum discrimination for normal and sensorineural hearing loss subjects. The results of the study indicated that normally hearing listeners do obtain maximum discrimination at MCL, while presentation of word discrimination material at MCL to sensorineural hearing loss listeners does not yield maximum discrimination. Further examination of the results would also contraindicate the use of any other method which incorporates single or dual presentation levels as a means of determining maximum discrimination for the sensorineural hearing loss listener."} {"id": "PMID:1275822", "title": "Pre- and postflight systolic time intervals during LBNP: the second manned Skylab mission.", "content": "After space flight of 59 d, Skylab 3 astronauts were stressed with lower body negative pressure (LBNP). During this stress procedure vectorcardiograms, pneumograms, phonocardiograms, and carotid pulse tracings were monitored and recorded onto analog tape. Accepted techniques were used to measure the intervals of systole. The postflight results were compared to multiple preflight tests and each of the three crewmen served as his own control. Immediately postflight, there were elevations in heart rate and blood pressure in response to a fixed level (-50 mm Hg) of LBNP. Total electromechanical systole, (Q-S2) I, was unchanged. Ejection time index (ETI) was depressed at rest and during stress, while pre-ejection period was elevated compared with preflight values. Systolic time intervals (STI) were within preflight limits after 1 month on earth in all crewmen. Resting STI returned sooner than did stressed STI. The magnitude and direction of STI in the postflight period were similar to those obtained from patients with moderate heart disease, although signs and symptoms were absent in the astronauts. However, the abnormality of the stressed STI persisted after both blood volume repletion and lowered afterload. These findings suggest a compromise in cardiac function, peripheral circulatory integrity, or both after exposure to long-duration space flight, and are consistent with findings reported after 3 weeks of absolute bedrest.", "contents": "Pre- and postflight systolic time intervals during LBNP: the second manned Skylab mission. After space flight of 59 d, Skylab 3 astronauts were stressed with lower body negative pressure (LBNP). During this stress procedure vectorcardiograms, pneumograms, phonocardiograms, and carotid pulse tracings were monitored and recorded onto analog tape. Accepted techniques were used to measure the intervals of systole. The postflight results were compared to multiple preflight tests and each of the three crewmen served as his own control. Immediately postflight, there were elevations in heart rate and blood pressure in response to a fixed level (-50 mm Hg) of LBNP. Total electromechanical systole, (Q-S2) I, was unchanged. Ejection time index (ETI) was depressed at rest and during stress, while pre-ejection period was elevated compared with preflight values. Systolic time intervals (STI) were within preflight limits after 1 month on earth in all crewmen. Resting STI returned sooner than did stressed STI. The magnitude and direction of STI in the postflight period were similar to those obtained from patients with moderate heart disease, although signs and symptoms were absent in the astronauts. However, the abnormality of the stressed STI persisted after both blood volume repletion and lowered afterload. These findings suggest a compromise in cardiac function, peripheral circulatory integrity, or both after exposure to long-duration space flight, and are consistent with findings reported after 3 weeks of absolute bedrest."} {"id": "PMID:1275819", "title": "Speech intelligibility and the use of hearing protectors.", "content": "On theoretical grounds, it is usually assumed that the use of hearing protectors in a noisy working environment has no influence upon speech intelligibility - in fact, may even increase it. In practice, however, people often do not wear hearing protectors, since these are widely believed to reduce speech intelligibility. In the present article, a description is given of an investigation, carried out among 537 subjects, into the influence of hearing protectors upon the speech intelligibility of people suffering from noise-induced hearing loss. From this analysis, it has become clear that the use of ear-muffs only leads to an improvement in speech intelligibility in persons who, according to their pure-tone audiogram, suffer from relatively small hearing losses. In general, it may be said that an increase in the severity of hearing losses will result in a reduced speech intelligibility.", "contents": "Speech intelligibility and the use of hearing protectors. On theoretical grounds, it is usually assumed that the use of hearing protectors in a noisy working environment has no influence upon speech intelligibility - in fact, may even increase it. In practice, however, people often do not wear hearing protectors, since these are widely believed to reduce speech intelligibility. In the present article, a description is given of an investigation, carried out among 537 subjects, into the influence of hearing protectors upon the speech intelligibility of people suffering from noise-induced hearing loss. From this analysis, it has become clear that the use of ear-muffs only leads to an improvement in speech intelligibility in persons who, according to their pure-tone audiogram, suffer from relatively small hearing losses. In general, it may be said that an increase in the severity of hearing losses will result in a reduced speech intelligibility."} {"id": "PMID:1275823", "title": "Determination of cardiac size following space missions of different durations: the second manned Skylab mission.", "content": "A simple method to estimate cardiac size from single frontal plane chest roentgenograms has been described. Pre- and postflight chest X-rays from Apollo 17, and Skylab 2 and 3 have been analyzed for changes in the cardiac silhouette size. The data obtained from the computed cardiothoracic areal ratios compared well with the clinical cardiothoracic diametral ratios (r = .86). Though an overall postflight decrease in cardiac size is evident, the mean difference was not statistically significant (n = 8). The individual decreases in the cardiac silhouette size postflight are thought to be due to decrements in intracardiac chamber volumes rather than in myocardial muscle mass.", "contents": "Determination of cardiac size following space missions of different durations: the second manned Skylab mission. A simple method to estimate cardiac size from single frontal plane chest roentgenograms has been described. Pre- and postflight chest X-rays from Apollo 17, and Skylab 2 and 3 have been analyzed for changes in the cardiac silhouette size. The data obtained from the computed cardiothoracic areal ratios compared well with the clinical cardiothoracic diametral ratios (r = .86). Though an overall postflight decrease in cardiac size is evident, the mean difference was not statistically significant (n = 8). The individual decreases in the cardiac silhouette size postflight are thought to be due to decrements in intracardiac chamber volumes rather than in myocardial muscle mass."} {"id": "PMID:1275824", "title": "Exercise cardiac output following Skylab missions: the second manned Skylab mission.", "content": "Cardiac output was measured during preflight and postflight exercise-stress tests on the Skylab astronauts. In the postflight tests immediately following the 28-, 59-, and 84-d earth orbital missions, the astronauts exhibited an approximate 30% decrease in cardiac output coupled with an approximate 50% decrease in cardiac stroke volume during exercise. These changes were accompanied by elevated heart rates and significant (p less than 0.01) increases in total systemic peripheral vascular resistance. Mean arterial pressure was unchanged. The hemodynamic alterations were transient in that all parameters returned to normal preflight values within 30 d of the end of the orbital period. Duration of the zero-G exposure did not appear to influence either the magnitude of the hemodynamic changes or the time-course of their return to normal. These results are discussed in relation to other cardiovascular findings and possible mechanisms responsible for the observations are outlined.", "contents": "Exercise cardiac output following Skylab missions: the second manned Skylab mission. Cardiac output was measured during preflight and postflight exercise-stress tests on the Skylab astronauts. In the postflight tests immediately following the 28-, 59-, and 84-d earth orbital missions, the astronauts exhibited an approximate 30% decrease in cardiac output coupled with an approximate 50% decrease in cardiac stroke volume during exercise. These changes were accompanied by elevated heart rates and significant (p less than 0.01) increases in total systemic peripheral vascular resistance. Mean arterial pressure was unchanged. The hemodynamic alterations were transient in that all parameters returned to normal preflight values within 30 d of the end of the orbital period. Duration of the zero-G exposure did not appear to influence either the magnitude of the hemodynamic changes or the time-course of their return to normal. These results are discussed in relation to other cardiovascular findings and possible mechanisms responsible for the observations are outlined."} {"id": "PMID:1275825", "title": "Hematology and immunology studies: the second manned Skylab mission.", "content": "The hematologic and immunologic functions of the Skylab 3 (second manned mission) astronauts were examined during the preflight, inflight, and postflight phases of the 59-d mission in order to evaluate the response to and/or the influence of the space flight environment. Most changes observed were subtle and did not represent a threat to the health and safety of the crewmen during orbital flight. Even the most significant change observed, a reduction in the circulating red cell mass, did not have a detrimental influence on the astronaut cardiovascular or exercise responses as evaluated by other experiment protocols. Considering the facts that the data were not collected under ideally controlled conditions and that the astronauts were in excellent physical condition, the results of these studies would seem to indicate that man can function quite well in the space flight environment of the Skylab orbiting workshop for extended periods of time.", "contents": "Hematology and immunology studies: the second manned Skylab mission. The hematologic and immunologic functions of the Skylab 3 (second manned mission) astronauts were examined during the preflight, inflight, and postflight phases of the 59-d mission in order to evaluate the response to and/or the influence of the space flight environment. Most changes observed were subtle and did not represent a threat to the health and safety of the crewmen during orbital flight. Even the most significant change observed, a reduction in the circulating red cell mass, did not have a detrimental influence on the astronaut cardiovascular or exercise responses as evaluated by other experiment protocols. Considering the facts that the data were not collected under ideally controlled conditions and that the astronauts were in excellent physical condition, the results of these studies would seem to indicate that man can function quite well in the space flight environment of the Skylab orbiting workshop for extended periods of time."} {"id": "PMID:1275826", "title": "Mineral and nitrogen balance study observations: the second manned Skylab mission.", "content": "A metabolic study of the effects of space flight on various chemical elements, particularly those with special revelance to the musculoskeletal system, was carried out on the three astronauts of the SL-3 mission for 21 d preflight, during the 60 d flight phase, and for 17 d postflight. The study required of the cooperating crewmen quite constant dietary intake, continuous 24-hour urine collections and total fecal collections. Urinary calcium was significantly increased during flight in all three crewmen with man-to-man variation in pattern and amount; the degree of calcium loss was, in general, similar to that in the prior study of the 28-d Skylab flight (SL-2). The similarity to bedrest immobilization in the pattern of urinary calcium increases and of total calcium shifts suggested that calcium losses would continue for a very long time. Significant losses of nitrogen and phosphorus occurred that were associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite vigorous exercise regimens during flight. It was concluded that these studies give warning that capable musculoskeletal function may be significantly impaired during prolonged space flights lasting 1.5 to 3 years unless protective measures are developed.", "contents": "Mineral and nitrogen balance study observations: the second manned Skylab mission. A metabolic study of the effects of space flight on various chemical elements, particularly those with special revelance to the musculoskeletal system, was carried out on the three astronauts of the SL-3 mission for 21 d preflight, during the 60 d flight phase, and for 17 d postflight. The study required of the cooperating crewmen quite constant dietary intake, continuous 24-hour urine collections and total fecal collections. Urinary calcium was significantly increased during flight in all three crewmen with man-to-man variation in pattern and amount; the degree of calcium loss was, in general, similar to that in the prior study of the 28-d Skylab flight (SL-2). The similarity to bedrest immobilization in the pattern of urinary calcium increases and of total calcium shifts suggested that calcium losses would continue for a very long time. Significant losses of nitrogen and phosphorus occurred that were associated with observed reduction in muscle tissue. Both mineral and muscle losses occurred despite vigorous exercise regimens during flight. It was concluded that these studies give warning that capable musculoskeletal function may be significantly impaired during prolonged space flights lasting 1.5 to 3 years unless protective measures are developed."} {"id": "PMID:1275827", "title": "Bone mineral changes: the second manned Skylab mission.", "content": "The mineral content of the central os calcis, and distal radius and ulna was measured by the monoenergetic photon absorptiometric technique pre- and postflight on the the SL-3 crewmen. No significant changes were observed in the radius and ulna. Only the SPT showed a loss in calcaneal mineral which slowly returned to preflight levels by the 87th postflight day.", "contents": "Bone mineral changes: the second manned Skylab mission. The mineral content of the central os calcis, and distal radius and ulna was measured by the monoenergetic photon absorptiometric technique pre- and postflight on the the SL-3 crewmen. No significant changes were observed in the radius and ulna. Only the SPT showed a loss in calcaneal mineral which slowly returned to preflight levels by the 87th postflight day."} {"id": "PMID:1275828", "title": "Measurement of a single tendon reflex in conjunction with a myogram: the second manned Skylab mission.", "content": "A generalized hyperreflexia was observed in Skylab 2 crewmembers during the immediate postflight clinical evaluations. Unfortunately, no provisions had been made to quantitate the observed phenomenon. The cause of the hyperreflexia was not readily apparent at the time of the observation. Reflex changes have been noted in several of the Russian cosmonauts after extended spaceflight. Prior to the launch of Skylab 3, it was decided to measure and record a single tendon reflex and, if possible, the associated muscle potential. Duration of the Achilles reflex immediately postflight showed a significant (p greater than 0.01) shortening for all three crewmen. The reflex duration exhibited further significant shortening from preflight values on the fourth day after recovery. At the 16th day measurement, there was a signficant lengthening of the reflex for crewmenber 2 and 3 while crewmember 1 showed some lengthening which was not significant. By 29 d postrecovery, the reflex time of crewmember 1 had returned to his preflight value while the other two crewmen continued to show a significant lengthening of the reflex, although both were showing trends toward their preflight values. The muscle potential intervals were shortened immediately postflight and remained shortened during the 29 d of postflight evaluation. Currently, work is in progress to correlate these findings with other observed anatomical, physical, and biochemical changes. Final conclusions and an in-depth statistical analysis will be presented at a later date.", "contents": "Measurement of a single tendon reflex in conjunction with a myogram: the second manned Skylab mission. A generalized hyperreflexia was observed in Skylab 2 crewmembers during the immediate postflight clinical evaluations. Unfortunately, no provisions had been made to quantitate the observed phenomenon. The cause of the hyperreflexia was not readily apparent at the time of the observation. Reflex changes have been noted in several of the Russian cosmonauts after extended spaceflight. Prior to the launch of Skylab 3, it was decided to measure and record a single tendon reflex and, if possible, the associated muscle potential. Duration of the Achilles reflex immediately postflight showed a significant (p greater than 0.01) shortening for all three crewmen. The reflex duration exhibited further significant shortening from preflight values on the fourth day after recovery. At the 16th day measurement, there was a signficant lengthening of the reflex for crewmenber 2 and 3 while crewmember 1 showed some lengthening which was not significant. By 29 d postrecovery, the reflex time of crewmember 1 had returned to his preflight value while the other two crewmen continued to show a significant lengthening of the reflex, although both were showing trends toward their preflight values. The muscle potential intervals were shortened immediately postflight and remained shortened during the 29 d of postflight evaluation. Currently, work is in progress to correlate these findings with other observed anatomical, physical, and biochemical changes. Final conclusions and an in-depth statistical analysis will be presented at a later date."} {"id": "PMID:1275829", "title": "Biostereometric analysis of body form: the second manned Skylab mission.", "content": "Biostereometrics is the measurement and the mathematical description of the three-dimensional form of biological objects. Stereophotogrammetry was used to derive the Cartesian coordinates of numerous points on the body surface of the Skylab crewmen, both before and after flight, on all three Skylab missions. Mathematical analysis of the coordinate description allows the computation of surface area and volume of the body, as well as the volume of body segments, and the area and shape of cross sections. Loss of body weight in the first two Skylab flight crews was accompanied by comparable loss of volume and little change in density. Volume loss wad divided about equally between the trunk and the legs; however, because the volume of the legs is less than that of the trunk, this finding represented a greater proportional volume loss in the legs. Comparison of cross-sectional areas suggests that the calf undergoes shrinkage to a greater extent than does the thigh. The suggested interpretation of these changes is that, during flight, a reduction in bulk of many of the body tissues occurs. This reduction is probably caused, at least in part, by disuse atrophy of skeletal muscles in the absence of gravity. The atrophy is lessened to some extent by the in-flight exercise program. The stereoscopic images of the crewmen from a permanent archival record of body form on which more detailed measurements may be made in the future.", "contents": "Biostereometric analysis of body form: the second manned Skylab mission. Biostereometrics is the measurement and the mathematical description of the three-dimensional form of biological objects. Stereophotogrammetry was used to derive the Cartesian coordinates of numerous points on the body surface of the Skylab crewmen, both before and after flight, on all three Skylab missions. Mathematical analysis of the coordinate description allows the computation of surface area and volume of the body, as well as the volume of body segments, and the area and shape of cross sections. Loss of body weight in the first two Skylab flight crews was accompanied by comparable loss of volume and little change in density. Volume loss wad divided about equally between the trunk and the legs; however, because the volume of the legs is less than that of the trunk, this finding represented a greater proportional volume loss in the legs. Comparison of cross-sectional areas suggests that the calf undergoes shrinkage to a greater extent than does the thigh. The suggested interpretation of these changes is that, during flight, a reduction in bulk of many of the body tissues occurs. This reduction is probably caused, at least in part, by disuse atrophy of skeletal muscles in the absence of gravity. The atrophy is lessened to some extent by the in-flight exercise program. The stereoscopic images of the crewmen from a permanent archival record of body form on which more detailed measurements may be made in the future."} {"id": "PMID:1275830", "title": "Crew health status and monitoring summary: the second manned Skylab mission.", "content": "We have attempted to show that objective data used to assess crew health comes to the responsible physicians from the laboratories of the experimenters in sporadic and overwhelming amounts, but rarely in the real-time or near real-time frame which is preferred. The crew surgeon generates little hard data by his own efforts. Because of these factors, whenever an over-all clinical assessment of a particular crewman's fitness to continue a mission is an immediate necessity, it must too often be given on what the clinician would consider less than adequate data. Beginning on MD 28, weekly conferences were held with senior NASA management to make a \"Go\" or \"No-Go\" recommendation to continue or terminate the mission. In the absence of absolute indications of an unacceptable declining crew health, a clinical judgment was required. To tighten the criteria for decision-making, the authors selected factors that seemed indicative of overall health and plotted them both as real-time and percentage changes from preflight means. Other plots of the most readily available real-time and near real-time data were also developed for this purpose. The major success of this effort was the initiation of a method which indicated interesting and worthwhile possibilities if continued, refined, and computerized for more rapid availability. Correlation of actual post-flight findings with results anticipated from this method was gratifying but not statistically defensible. Whether or not this method would have forewarned of a serious decrement in crewmen's health cannot be known because, in fact, they were healthy and remain healthy.", "contents": "Crew health status and monitoring summary: the second manned Skylab mission. We have attempted to show that objective data used to assess crew health comes to the responsible physicians from the laboratories of the experimenters in sporadic and overwhelming amounts, but rarely in the real-time or near real-time frame which is preferred. The crew surgeon generates little hard data by his own efforts. Because of these factors, whenever an over-all clinical assessment of a particular crewman's fitness to continue a mission is an immediate necessity, it must too often be given on what the clinician would consider less than adequate data. Beginning on MD 28, weekly conferences were held with senior NASA management to make a \"Go\" or \"No-Go\" recommendation to continue or terminate the mission. In the absence of absolute indications of an unacceptable declining crew health, a clinical judgment was required. To tighten the criteria for decision-making, the authors selected factors that seemed indicative of overall health and plotted them both as real-time and percentage changes from preflight means. Other plots of the most readily available real-time and near real-time data were also developed for this purpose. The major success of this effort was the initiation of a method which indicated interesting and worthwhile possibilities if continued, refined, and computerized for more rapid availability. Correlation of actual post-flight findings with results anticipated from this method was gratifying but not statistically defensible. Whether or not this method would have forewarned of a serious decrement in crewmen's health cannot be known because, in fact, they were healthy and remain healthy."} {"id": "PMID:1275831", "title": "Laboratory investigation of \"biorhythms\".", "content": "Three subjects were tested on an information processing task on a daily basis for a period of 70 d. Performance measurement included reaction time, movement time, and information processing rate. The data set obtained was subjected to Fast Fourier Transforms (FFT) in an attempt to identify periodicities in performance. Twelve significant harmonics were identified and nine were found to be within 1 d of at least one of the cycles hypothesized by the theory of \"biorhythms.\" The probability of this occurring by chance is remote (p less than 0.05), assuming a uniform distribution of significant amplitude. The results were interpreted as suggesting the possibility of a biorhythmic influence in the performance of the task.", "contents": "Laboratory investigation of \"biorhythms\". Three subjects were tested on an information processing task on a daily basis for a period of 70 d. Performance measurement included reaction time, movement time, and information processing rate. The data set obtained was subjected to Fast Fourier Transforms (FFT) in an attempt to identify periodicities in performance. Twelve significant harmonics were identified and nine were found to be within 1 d of at least one of the cycles hypothesized by the theory of \"biorhythms.\" The probability of this occurring by chance is remote (p less than 0.05), assuming a uniform distribution of significant amplitude. The results were interpreted as suggesting the possibility of a biorhythmic influence in the performance of the task."} {"id": "PMID:1275832", "title": "Review of the effects of infrasound on man.", "content": "Claims that infrasound adversely affects human performance, makes people \"drunk,\" and directly elicits nystagmus, have not been clearly demonstrated in any experimental study. The effects obtained at low intensity levels of 105 to 120 dB, if they can be substantiated at all, have been exaggerated. Recent well-designed studies conducted at higher intensity levels have found no adverse effects of infrasound on reaction time or human equilibrium. The levels at which infrasound becomes a hazard to man are still unknown. However, the hazardous levels are certain to be much higher than have been suggested in some of the literature. The preliminary exposure limits which were proposed several years ago for use in the U.S.A. are still considered safe and adequate based on present knowledge. Caution is necessary in future research because artifacts produced by faulty experimental procedures can suggest genuine psychological or physiological effects.", "contents": "Review of the effects of infrasound on man. Claims that infrasound adversely affects human performance, makes people \"drunk,\" and directly elicits nystagmus, have not been clearly demonstrated in any experimental study. The effects obtained at low intensity levels of 105 to 120 dB, if they can be substantiated at all, have been exaggerated. Recent well-designed studies conducted at higher intensity levels have found no adverse effects of infrasound on reaction time or human equilibrium. The levels at which infrasound becomes a hazard to man are still unknown. However, the hazardous levels are certain to be much higher than have been suggested in some of the literature. The preliminary exposure limits which were proposed several years ago for use in the U.S.A. are still considered safe and adequate based on present knowledge. Caution is necessary in future research because artifacts produced by faulty experimental procedures can suggest genuine psychological or physiological effects."} {"id": "PMID:1275833", "title": "Braking saccade--a new fast eye movement.", "content": "A new type of fast eye movement (FEM) is described whose main function is to stop a runaway slow eye movement (SEM). It conforms to the velocity-amplitude relationship characteristic of other types of saccades. The identification of this FEM is the result of examination of the many waveforms manifested by subjects with congenital nystagmus. It is a common, repeatable phenomenon present in all subjects with any of six different types of nystagmus waveform. The fact that braking saccades reset SEM to zero velocity, whereas no other type of saccade interacts with SEM, indicates a developmental mechanism in such subjects.", "contents": "Braking saccade--a new fast eye movement. A new type of fast eye movement (FEM) is described whose main function is to stop a runaway slow eye movement (SEM). It conforms to the velocity-amplitude relationship characteristic of other types of saccades. The identification of this FEM is the result of examination of the many waveforms manifested by subjects with congenital nystagmus. It is a common, repeatable phenomenon present in all subjects with any of six different types of nystagmus waveform. The fact that braking saccades reset SEM to zero velocity, whereas no other type of saccade interacts with SEM, indicates a developmental mechanism in such subjects."} {"id": "PMID:1275834", "title": "Visual accommodation variations during trans-atlantic cockpit duties.", "content": "Twenty airline pilots measured their near point of accommodation employing a modified Princes' Rule. Measurements were performed periodically travelling east- and west-bound. Five clerical control subjects performed the same measurements over 2 consecutive days. The ranges of variability of the nearpoint of accommodation were compared between the two groups, directions and days. No statistically significant differences in the variability of accommodation were found in the comparisons.", "contents": "Visual accommodation variations during trans-atlantic cockpit duties. Twenty airline pilots measured their near point of accommodation employing a modified Princes' Rule. Measurements were performed periodically travelling east- and west-bound. Five clerical control subjects performed the same measurements over 2 consecutive days. The ranges of variability of the nearpoint of accommodation were compared between the two groups, directions and days. No statistically significant differences in the variability of accommodation were found in the comparisons."} {"id": "PMID:1275835", "title": "ECG monitoring of heart failure and pilot load/overload by the Vesla seat pad.", "content": "Heart failure has caused sudden incapacitation of pilots in command of commerical airliners. These fatal episodes have occurred in connection with takeoffs and landings, and have resulted in incidents as well as major accidents in which more than 300 people have been killed. Coronary attack may be verified later at autopsy. Sudden cardiac arrest or serious episodes, such as ventricular tachycardia, usually cannot be detected at autopsy. A number of accidents due to unknown reasons or to \"pilot error\" can be due to, and some probably are, cardiac breakdown. It is today possible, with the Vesla Seat Pad, to monitor the pilot's ECG. The Vesla Seat Pad is a device for biomedical monitoring of ECG signals from human subjects without attachment to the subjects of any leads or sensor devices. The Vesla pad on which a human subject may rest, requires no power source. It is capable of obtaining appropriate ECG signals, transmitted to the pad through the medium of the subject's perspiration, for monitoring the subject's heart action. ECG signals, together with other data, can be electronically processed and used to warn the co-pilot and tower of impending hazard. The \"dead man's button\" with an OVERLOAD warning system could greatly, when taken into use, improve flying safety.", "contents": "ECG monitoring of heart failure and pilot load/overload by the Vesla seat pad. Heart failure has caused sudden incapacitation of pilots in command of commerical airliners. These fatal episodes have occurred in connection with takeoffs and landings, and have resulted in incidents as well as major accidents in which more than 300 people have been killed. Coronary attack may be verified later at autopsy. Sudden cardiac arrest or serious episodes, such as ventricular tachycardia, usually cannot be detected at autopsy. A number of accidents due to unknown reasons or to \"pilot error\" can be due to, and some probably are, cardiac breakdown. It is today possible, with the Vesla Seat Pad, to monitor the pilot's ECG. The Vesla Seat Pad is a device for biomedical monitoring of ECG signals from human subjects without attachment to the subjects of any leads or sensor devices. The Vesla pad on which a human subject may rest, requires no power source. It is capable of obtaining appropriate ECG signals, transmitted to the pad through the medium of the subject's perspiration, for monitoring the subject's heart action. ECG signals, together with other data, can be electronically processed and used to warn the co-pilot and tower of impending hazard. The \"dead man's button\" with an OVERLOAD warning system could greatly, when taken into use, improve flying safety."} {"id": "PMID:1275836", "title": "Simulated aircraft disaster instructional exercise at Baltimore-Washington International Airport.", "content": "A major, simulated aircraft disaster exercise was held in September of 1974 at the Baltimore-Washington International Airport in Maryland. The significant aspects of community involvement and specialized airport emergency planning were tested during this simulation. This paper presents an evaluation of the experience of the various elements in this exercise. The critical matter of having a system of runners to substitute for a failure within the mobile command post is stressed. Also, the importance of adequate telephone facilities for communication with the fire/rescue stations and community hospitals is highlighted. Many other small and seemingly unimportant items are found to be of considerable significance during the handling of disasters. A strong case is made for periodic disaster simulations to maintain an efficient broadly-based apparatus for handling such disasters, should they occur.", "contents": "Simulated aircraft disaster instructional exercise at Baltimore-Washington International Airport. A major, simulated aircraft disaster exercise was held in September of 1974 at the Baltimore-Washington International Airport in Maryland. The significant aspects of community involvement and specialized airport emergency planning were tested during this simulation. This paper presents an evaluation of the experience of the various elements in this exercise. The critical matter of having a system of runners to substitute for a failure within the mobile command post is stressed. Also, the importance of adequate telephone facilities for communication with the fire/rescue stations and community hospitals is highlighted. Many other small and seemingly unimportant items are found to be of considerable significance during the handling of disasters. A strong case is made for periodic disaster simulations to maintain an efficient broadly-based apparatus for handling such disasters, should they occur."} {"id": "PMID:1275837", "title": "Economical oxygen-delivery system.", "content": "The conservation of aircraft oxygen supplies is becoming of considerable interest to the Air Force. Onboard oxygen-generating systems are being developed which could support an aircrew if oxygen produced by these systems were used conservatively. These experiments studied the conservation potential of a rebreather bag placed in a vented container near the regulator in an oxygen-delivery system. The bag's volume was close to that of the subject's physiologic dead space. When the subject exhaled, oxygen in the mouth, trachea, and mask dead space went to the rebreather bag, to be rebreathed with the next breath. The CO2-contaminated oxygen from the alveoli was vented to the cabin. The dead-space oxygen could be separated from contaminated oxygen because dead-space air is exhaled first with each breath. When the rebreather-bag volume matched the subject's physiologic dead space so that no CO2 accumulated, a 30% oxygen savings was realized. When the bag was large enough to realize a 50% savings, CO2 accumulation was only 2%.", "contents": "Economical oxygen-delivery system. The conservation of aircraft oxygen supplies is becoming of considerable interest to the Air Force. Onboard oxygen-generating systems are being developed which could support an aircrew if oxygen produced by these systems were used conservatively. These experiments studied the conservation potential of a rebreather bag placed in a vented container near the regulator in an oxygen-delivery system. The bag's volume was close to that of the subject's physiologic dead space. When the subject exhaled, oxygen in the mouth, trachea, and mask dead space went to the rebreather bag, to be rebreathed with the next breath. The CO2-contaminated oxygen from the alveoli was vented to the cabin. The dead-space oxygen could be separated from contaminated oxygen because dead-space air is exhaled first with each breath. When the rebreather-bag volume matched the subject's physiologic dead space so that no CO2 accumulated, a 30% oxygen savings was realized. When the bag was large enough to realize a 50% savings, CO2 accumulation was only 2%."} {"id": "PMID:1275838", "title": "Study of the microbiological environment within long- and medium-range Canadian Forces aircraft.", "content": "Because of a possible requirement to carry patients with highly virulent communicable diseases, a study was undertaken to observe smoke patterns within Canadian Forces transport aircraft. This was followed by the quantitative evaluation of the spread on non-pathogenic organisms disseminated within a Boeing 707 and a C13OE (Hercules). Thirdly, an attempt to recover respiratory tract viruses during transatlantic flights was made. Smoke patterns showed that an infected patient should be placed at the rear of the aircraft. The spread of the nonpathogenic organisms in a 707 indicated that contamination was largely confined to the rear, except when the aircraft was in an unpressurized mode. In the C13OE, contamination was shown to occur throughout the whole aircraft. No respiratory tract viruses were recovered during the transatlantic flights. It is essential that a 707 should be utilized for aeromedical evacuations. If a C13OE is being considered, then a portable self-contained isolation care unit is mandatory.", "contents": "Study of the microbiological environment within long- and medium-range Canadian Forces aircraft. Because of a possible requirement to carry patients with highly virulent communicable diseases, a study was undertaken to observe smoke patterns within Canadian Forces transport aircraft. This was followed by the quantitative evaluation of the spread on non-pathogenic organisms disseminated within a Boeing 707 and a C13OE (Hercules). Thirdly, an attempt to recover respiratory tract viruses during transatlantic flights was made. Smoke patterns showed that an infected patient should be placed at the rear of the aircraft. The spread of the nonpathogenic organisms in a 707 indicated that contamination was largely confined to the rear, except when the aircraft was in an unpressurized mode. In the C13OE, contamination was shown to occur throughout the whole aircraft. No respiratory tract viruses were recovered during the transatlantic flights. It is essential that a 707 should be utilized for aeromedical evacuations. If a C13OE is being considered, then a portable self-contained isolation care unit is mandatory."} {"id": "PMID:1275839", "title": "Bradycardia induced by negative acceleration.", "content": "Four volunteers were subjected to negative acceleration in a human centrifuge for the purpose of testing a standard lap belt. Three subjects developed a sinus bradycardia. The fourth developed a sinus arrest with a junctional rhythm at -2 G. With return to +1 G, the sinus mechanism recovered with a prolonged P-R interval. Within 2 h, the P-R interval returned to normal. Negative acceleration maneuvers, well within the capabilities of high-performance aircraft, can effect marked changes in the cardiac rhythm. This phenomenon appears to be vagally induced and is remarkably well tolerated.", "contents": "Bradycardia induced by negative acceleration. Four volunteers were subjected to negative acceleration in a human centrifuge for the purpose of testing a standard lap belt. Three subjects developed a sinus bradycardia. The fourth developed a sinus arrest with a junctional rhythm at -2 G. With return to +1 G, the sinus mechanism recovered with a prolonged P-R interval. Within 2 h, the P-R interval returned to normal. Negative acceleration maneuvers, well within the capabilities of high-performance aircraft, can effect marked changes in the cardiac rhythm. This phenomenon appears to be vagally induced and is remarkably well tolerated."} {"id": "PMID:1275840", "title": "Potassium losses in sweat under heat stress.", "content": "Six healthy, heat-acclimatized subjects were exposed to different hot and humid environments in a climatic chamber and sodium, potassium, and chloride concentrations in their sweat, urine, and blood were determined. The concentration of potassium in sweat was found to be considerably higher than that in the plasma, whereas that of sodium and chloride was very much lower. The concentration of potassium in urine was also 8-12 times higher than that in the plasma as compared to 0.5 to 1.5 times higher for sodium and chloride. The total daily computed losses of potassium in sweat and urine, of a person working in severe heat in the tropics, can be about 116 mEq as against a dietary intake of 97 mEq/d, thereby resulting in negative potassium balance. The potassium depletion in sweat, even in acclimatized Indians, is thus heavy and is likely to play an important role in the causation of heat-illness.", "contents": "Potassium losses in sweat under heat stress. Six healthy, heat-acclimatized subjects were exposed to different hot and humid environments in a climatic chamber and sodium, potassium, and chloride concentrations in their sweat, urine, and blood were determined. The concentration of potassium in sweat was found to be considerably higher than that in the plasma, whereas that of sodium and chloride was very much lower. The concentration of potassium in urine was also 8-12 times higher than that in the plasma as compared to 0.5 to 1.5 times higher for sodium and chloride. The total daily computed losses of potassium in sweat and urine, of a person working in severe heat in the tropics, can be about 116 mEq as against a dietary intake of 97 mEq/d, thereby resulting in negative potassium balance. The potassium depletion in sweat, even in acclimatized Indians, is thus heavy and is likely to play an important role in the causation of heat-illness."} {"id": "PMID:1275841", "title": "Amelioration of the symptoms of acute mountain sickness by staging and acetazolamide.", "content": "Treatment by 4 d of residence at 1600 m plus the administration of 500 mg acetazolamide b.i.d. for the last 2 d at 1600 m and the first 2 d at 4300 m was compared with no treatment prior to ascent to 4300 m for prophylaxis of acute mountain sickness. The treatment successfully prevented almost all symptoms of acute mountain sickness. It had no effect on the diminished capacity for maximal or prolonged heavy physical work. The treatment produced a relative acidosis and a comparatively greater arterial oxygen tension at 4300 m.", "contents": "Amelioration of the symptoms of acute mountain sickness by staging and acetazolamide. Treatment by 4 d of residence at 1600 m plus the administration of 500 mg acetazolamide b.i.d. for the last 2 d at 1600 m and the first 2 d at 4300 m was compared with no treatment prior to ascent to 4300 m for prophylaxis of acute mountain sickness. The treatment successfully prevented almost all symptoms of acute mountain sickness. It had no effect on the diminished capacity for maximal or prolonged heavy physical work. The treatment produced a relative acidosis and a comparatively greater arterial oxygen tension at 4300 m."} {"id": "PMID:1275842", "title": "Mechanism of lung damage in explosive decompression.", "content": "It is known that pressure equalization via the trachea may diminish or prevent lung damage in explosive decompression. In this report, evidence is presented which demonstrates that closure of the trachea does not affect lethality in mice exposed to maximally rapid decompression. This observation suggests that in maximally rapid decompression the lungs and thorax may be treated as a closed system to which Boyle's Law might be applicable.", "contents": "Mechanism of lung damage in explosive decompression. It is known that pressure equalization via the trachea may diminish or prevent lung damage in explosive decompression. In this report, evidence is presented which demonstrates that closure of the trachea does not affect lethality in mice exposed to maximally rapid decompression. This observation suggests that in maximally rapid decompression the lungs and thorax may be treated as a closed system to which Boyle's Law might be applicable."} {"id": "PMID:1275843", "title": "Algorithm for analyses of saccadic eye movements using a digital computer.", "content": "An algorithm for digital computer analyses of electro-oculographically recorded saccardic eye movements is presented. From a brief, 4-min recording session detailed statistical information about saccade velocity, accuracy, and delay time can be obtained. Since this data is not significantly altered by practice of motivational factors, it provides a sensitive functional test of the extra-ocular muscles and their brain control system.", "contents": "Algorithm for analyses of saccadic eye movements using a digital computer. An algorithm for digital computer analyses of electro-oculographically recorded saccardic eye movements is presented. From a brief, 4-min recording session detailed statistical information about saccade velocity, accuracy, and delay time can be obtained. Since this data is not significantly altered by practice of motivational factors, it provides a sensitive functional test of the extra-ocular muscles and their brain control system."} {"id": "PMID:1275844", "title": "Method for determining pilot stress through analysis of voice communication.", "content": "Factors inherent in aircraft communication systems hinder customary approaches to voice analysis in the determination of the degree of stress experienced by a pilot during an inflight emergency. By means of a sound spectrogram, the mean vibration space of a voice can be analyzed if the space between the vertical deflections of the vowel sounds is calculated in micrometers. The vibration space shift rate (VSSR) is calculated by comparing the widest vibration space of the voice during the normal phase of the same flight (standard vibration space: SVS) with that encountered during the emergency situation (EVS) by the following formula: VSSR = ((SUS-EVS)/SUS) X 100%. The number of measuring points in each case differs in regard to the length of communication during the emergency. The VSSR can be divided into three phases - normal, urgent, and emergency - each with three grades of 0.5 S.D. apiece.", "contents": "Method for determining pilot stress through analysis of voice communication. Factors inherent in aircraft communication systems hinder customary approaches to voice analysis in the determination of the degree of stress experienced by a pilot during an inflight emergency. By means of a sound spectrogram, the mean vibration space of a voice can be analyzed if the space between the vertical deflections of the vowel sounds is calculated in micrometers. The vibration space shift rate (VSSR) is calculated by comparing the widest vibration space of the voice during the normal phase of the same flight (standard vibration space: SVS) with that encountered during the emergency situation (EVS) by the following formula: VSSR = ((SUS-EVS)/SUS) X 100%. The number of measuring points in each case differs in regard to the length of communication during the emergency. The VSSR can be divided into three phases - normal, urgent, and emergency - each with three grades of 0.5 S.D. apiece."} {"id": "PMID:1275845", "title": "Comparative muscular strength of men and women: a review of the literature.", "content": "The results from nine separate studies reporting comparable static and dynamic muscle strength measurements between men and women have been reviewed. The statistical data from these studies are presented in graphical and tabular form illustrating, when appropriate, the mean +/- 1 S.D., and the mean percentage difference between men and women for the given measurement.", "contents": "Comparative muscular strength of men and women: a review of the literature. The results from nine separate studies reporting comparable static and dynamic muscle strength measurements between men and women have been reviewed. The statistical data from these studies are presented in graphical and tabular form illustrating, when appropriate, the mean +/- 1 S.D., and the mean percentage difference between men and women for the given measurement."} {"id": "PMID:1275846", "title": "Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping.", "content": "Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping.", "contents": "Prolactin, thyrotropin, and growth hormone release during stress associated with parachute jumping. Prolactin, growth hormone, and thyrotropin (TSH) release during the stress of parachute jumping has been evaluated in 14 male subjects. Subjects were studied at several times before and immediately after their first military parachute jump. All three hormones had risen significantly 1 to 14 min after the jump, compared to mean levels measured immediately beforehand. Earlier studies of physical exercise by ourselves and others would suggest that emotional stress played a role in producing changes of this magnitude. We conclude that prolactin, TSH, and growth hormone are released in physiologically significant amounts in association with the stress of parachute jumping."} {"id": "PMID:1275847", "title": "Cerebral air embolism and cerebral edema: one regimen of treatment.", "content": "A case of cerebral air embolism responding immediately to compression to 6 atm is described. The patient, however, developed apparent cerebral edema while being decompressed. Subsequent recompression on oxygen was carried out twice daily at 60 ft (18 m, 2.8 ATA) for 60 min until the patient's symptoms had nearly cleared. While a number of other medications known to affect intracranial pressure were used, objective clinical improvement was noted only after hyperbaric oxygen. A question is raised of whether there is an association between the development of cerebral edema and the administration of intravenous 5% glucose in water.", "contents": "Cerebral air embolism and cerebral edema: one regimen of treatment. A case of cerebral air embolism responding immediately to compression to 6 atm is described. The patient, however, developed apparent cerebral edema while being decompressed. Subsequent recompression on oxygen was carried out twice daily at 60 ft (18 m, 2.8 ATA) for 60 min until the patient's symptoms had nearly cleared. While a number of other medications known to affect intracranial pressure were used, objective clinical improvement was noted only after hyperbaric oxygen. A question is raised of whether there is an association between the development of cerebral edema and the administration of intravenous 5% glucose in water."} {"id": "PMID:1275848", "title": "Planning an airport disaster drill.", "content": "The authors have prepared this paper to serve as a guide for planning airport disaster drills, particularly at the major air carrier airports. Their recommendations are subject to change according to the needs of the individual airport and the particular circumstances that may be present. Basically, the recommendations are founded on the experience gained by participation in planning and carrying out five separate emergency or disaster drills (Oakland International Airport 1, San Francisco International Airport 2, Los Angeles International Airport 2). The authors also have been involved in a total of three additional disaster drills in California and have been involved in one way or another in an additional 19 airport disaster drills throughout the United States. The presentation is divided into segments according to activity. However, it should be noted that there is a cohesiveness necessary for disaster planning if the drill is to be successful.", "contents": "Planning an airport disaster drill. The authors have prepared this paper to serve as a guide for planning airport disaster drills, particularly at the major air carrier airports. Their recommendations are subject to change according to the needs of the individual airport and the particular circumstances that may be present. Basically, the recommendations are founded on the experience gained by participation in planning and carrying out five separate emergency or disaster drills (Oakland International Airport 1, San Francisco International Airport 2, Los Angeles International Airport 2). The authors also have been involved in a total of three additional disaster drills in California and have been involved in one way or another in an additional 19 airport disaster drills throughout the United States. The presentation is divided into segments according to activity. However, it should be noted that there is a cohesiveness necessary for disaster planning if the drill is to be successful."} {"id": "PMID:1275858", "title": "Nuclear size and chromatin concentration in transitional cell carcinoma of the human urinary bladder.", "content": "Feulgen-stained cell nuclei from 25 specimens from transitional cell carcinoma of the human bladder were examined by means of cytophotometric scanning measurements. The mean values of nuclear area, DNA-content and chromatin concentration after scanning of a hundred nuclei per specimen were compared with those from a control group consisting of 10 specimens of normal transitional cell epithelium. Within the same ploidy class the more differentiated carcinoma cells showed nuclear enlargement and decrease of mean chromatin concentration. Undifferentiated tumours could have the same or higher mean chromatin concentration as the control group owing to the many highpolyploid nuclei. Undifferentiated tumours contained numerous giant nuclei, whereas these were rare in well differentiated carcinoma. When allowances were made for variations due to fixation and staining measurement of the nuclear area could serve as means of differentiating between normal and cancer nuclei with a high degree of statistic probability. The question whether nuclear enlargement and decreased chromatin concentration represent physiological changes or are entirely or partly the result of chemical carcinogenesis is discussed.", "contents": "Nuclear size and chromatin concentration in transitional cell carcinoma of the human urinary bladder. Feulgen-stained cell nuclei from 25 specimens from transitional cell carcinoma of the human bladder were examined by means of cytophotometric scanning measurements. The mean values of nuclear area, DNA-content and chromatin concentration after scanning of a hundred nuclei per specimen were compared with those from a control group consisting of 10 specimens of normal transitional cell epithelium. Within the same ploidy class the more differentiated carcinoma cells showed nuclear enlargement and decrease of mean chromatin concentration. Undifferentiated tumours could have the same or higher mean chromatin concentration as the control group owing to the many highpolyploid nuclei. Undifferentiated tumours contained numerous giant nuclei, whereas these were rare in well differentiated carcinoma. When allowances were made for variations due to fixation and staining measurement of the nuclear area could serve as means of differentiating between normal and cancer nuclei with a high degree of statistic probability. The question whether nuclear enlargement and decreased chromatin concentration represent physiological changes or are entirely or partly the result of chemical carcinogenesis is discussed."} {"id": "PMID:1275859", "title": "The significance of random sample size in flow-through photometric prescreening in cervical cytology.", "content": "The determination of nuclear DNA content by flow-through photometry is employed as a prescreening procedure in cervical cytology. The goal of a prescreening procedure is to obtain the smallest possible number of false negative findings with an economically acceptable number of false positive findings, which must be retested. False negative findings result from the often low relative frequency of atypical cells in a mixed population of normal and atypical cells. Only between 10,000 and 50,000 cells are contained in a random sample from the total suspended smear material. It was the purpose of this study to investigate whether a flow-through photometric study of the entire suspension and thus the larger absolute frequency of atypical cells mught lead to a decrease in false negative results. Flow-through photometric evaluation of the entire smear material is not superior to measurement of a random sample of 10,000-50,000 cells. 1. The relative frequency of atypical cells is unchanged, and thus also the proportion of false negative findings. 2. The number of false positive findings increases by 10% due to the inclusion of aggregates at the bottom of the preparation. 3. The measuring time is increased 10-fold, thus making the prescreening procedure uneconomical.", "contents": "The significance of random sample size in flow-through photometric prescreening in cervical cytology. The determination of nuclear DNA content by flow-through photometry is employed as a prescreening procedure in cervical cytology. The goal of a prescreening procedure is to obtain the smallest possible number of false negative findings with an economically acceptable number of false positive findings, which must be retested. False negative findings result from the often low relative frequency of atypical cells in a mixed population of normal and atypical cells. Only between 10,000 and 50,000 cells are contained in a random sample from the total suspended smear material. It was the purpose of this study to investigate whether a flow-through photometric study of the entire suspension and thus the larger absolute frequency of atypical cells mught lead to a decrease in false negative results. Flow-through photometric evaluation of the entire smear material is not superior to measurement of a random sample of 10,000-50,000 cells. 1. The relative frequency of atypical cells is unchanged, and thus also the proportion of false negative findings. 2. The number of false positive findings increases by 10% due to the inclusion of aggregates at the bottom of the preparation. 3. The measuring time is increased 10-fold, thus making the prescreening procedure uneconomical."} {"id": "PMID:1275860", "title": "[Influence of calcitonin on the quantitative cytoarchitecture of juvenile rats, a morphometric study on rat hepatocytes (author's transl)].", "content": "1. Using ultrastructural-morphometric analysis of liver parenchymal cells, following long term calcitonin administration, the suggestion that calcitonin influences intermediate as well as calcium metabolism has been strengthened. 2. The experiments were performed with 10 young male Wiatar rats. 5 animals received salmon calcitonin intraperitoneally every day for 6 weeks, 5 untreated animals served as controls. All animals had free access to water and Altromin-R-standard diet. The morphometric investigations were carried out by a method analogous to that of Weibel (1969). 3. By comparison with controls smaller cells and nuclei were seen. Following calcitonin treatment the mitochondrial content of liver parenchymal cells was markedly reduced. On the other hand the surface of cristae was doubled. A proportional membrane and enzyme production in the sense of an adaption, or a disproportional membrane and enzyme synthesis as a misadaption is discussed as the pathogenetic mechanism. Furthermore the number as well as the volume of peroxisome, and lysosomes was reduced. Total liver calcium decreased, whereas serum calcium concentration increased slightly. This can be explained through raised renal reabsorption as a compensatory effect of parathyroid hormone.", "contents": "[Influence of calcitonin on the quantitative cytoarchitecture of juvenile rats, a morphometric study on rat hepatocytes (author's transl)]. 1. Using ultrastructural-morphometric analysis of liver parenchymal cells, following long term calcitonin administration, the suggestion that calcitonin influences intermediate as well as calcium metabolism has been strengthened. 2. The experiments were performed with 10 young male Wiatar rats. 5 animals received salmon calcitonin intraperitoneally every day for 6 weeks, 5 untreated animals served as controls. All animals had free access to water and Altromin-R-standard diet. The morphometric investigations were carried out by a method analogous to that of Weibel (1969). 3. By comparison with controls smaller cells and nuclei were seen. Following calcitonin treatment the mitochondrial content of liver parenchymal cells was markedly reduced. On the other hand the surface of cristae was doubled. A proportional membrane and enzyme production in the sense of an adaption, or a disproportional membrane and enzyme synthesis as a misadaption is discussed as the pathogenetic mechanism. Furthermore the number as well as the volume of peroxisome, and lysosomes was reduced. Total liver calcium decreased, whereas serum calcium concentration increased slightly. This can be explained through raised renal reabsorption as a compensatory effect of parathyroid hormone."} {"id": "PMID:1275861", "title": "Effect of alcohol on ganglion cells in the superior cervical ganglia of young rats.", "content": "Light and electron microscopic studies on the superior cervical ganglia of young albino rats after 4 weeks of 32% alcohol ingestion indicate striking degenerative changes in sympathetic nerve cells.", "contents": "Effect of alcohol on ganglion cells in the superior cervical ganglia of young rats. Light and electron microscopic studies on the superior cervical ganglia of young albino rats after 4 weeks of 32% alcohol ingestion indicate striking degenerative changes in sympathetic nerve cells."} {"id": "PMID:1275862", "title": "Intracerebral metastatic malignant teratoma in the region of the optic chiasm.", "content": "An intracerebral metastatic teratoma in a 10-year-old girl is described. This is only the third case that has been reported in literature. Autopsy revealed a cystic tumour measuring 4 cm in diameter in the region of the optic chiasm. Microscopic examination showed that it contained all 3 germinal layers. It was classified in accordance with the criteria of Collins and Pugh as a malignant teratoma intermediate A (M.T.I.A.). Metastases had developed upstream and downstream of the CSF flow in the rostral segment of the pons, the medulla oblongata and the cerebellum as well as in the region of the posterior commissure above the lamina quadrigemina and the pineal body. In addition, there were also leptomeningeal metastases in the region of the left Sylvian furrow. The different opinions of various authors regarding the malignant potency of intracranial teratomas are raised and discussed.", "contents": "Intracerebral metastatic malignant teratoma in the region of the optic chiasm. An intracerebral metastatic teratoma in a 10-year-old girl is described. This is only the third case that has been reported in literature. Autopsy revealed a cystic tumour measuring 4 cm in diameter in the region of the optic chiasm. Microscopic examination showed that it contained all 3 germinal layers. It was classified in accordance with the criteria of Collins and Pugh as a malignant teratoma intermediate A (M.T.I.A.). Metastases had developed upstream and downstream of the CSF flow in the rostral segment of the pons, the medulla oblongata and the cerebellum as well as in the region of the posterior commissure above the lamina quadrigemina and the pineal body. In addition, there were also leptomeningeal metastases in the region of the left Sylvian furrow. The different opinions of various authors regarding the malignant potency of intracranial teratomas are raised and discussed."} {"id": "PMID:1275865", "title": "The fine structure of dense lysosomes isolated from rat spleen.", "content": "A dense fraction from rat spleen was shown to consist of membrane bound organelles of varying shape and size which were packed with electron dense particles with the appearance of ferritin. Electron microscope microanalysis confirmed that iron was present in the organelles and the amount correlated with the density as noted in transmission electron microscopy. The organelles also stained, positively for acid phosphatase and, therefore, confirmed the biochemical findings that dense lysosomes (L30) had been isolated. The role lysosomes play in the degradation of red blood cells, and as possible sites of iron storage, are briefly discussed.", "contents": "The fine structure of dense lysosomes isolated from rat spleen. A dense fraction from rat spleen was shown to consist of membrane bound organelles of varying shape and size which were packed with electron dense particles with the appearance of ferritin. Electron microscope microanalysis confirmed that iron was present in the organelles and the amount correlated with the density as noted in transmission electron microscopy. The organelles also stained, positively for acid phosphatase and, therefore, confirmed the biochemical findings that dense lysosomes (L30) had been isolated. The role lysosomes play in the degradation of red blood cells, and as possible sites of iron storage, are briefly discussed."} {"id": "PMID:1275866", "title": "Dysgerminoma in Turner's syndrome.", "content": "The importance of the Y-chromosome for the germ cell tumour development in gonadal dysgenesis has been emphasized many times. In contrast, only two cases of dysgerminoma or gonadoblastoma had been published so far in the XO-Turner's syndrome. With this report, another case of Turner's syndrome developing a dysgerminoma in a gonadal streak is presented. No Y-chromosome containing stemline could be detected in the patient nor in the tumour. A primary genetic etiology or a mechanism related to early secondary regression or dysgenesis of the gonad are discussed as causative factors in germ cell tumour development within gonadal streaks.", "contents": "Dysgerminoma in Turner's syndrome. The importance of the Y-chromosome for the germ cell tumour development in gonadal dysgenesis has been emphasized many times. In contrast, only two cases of dysgerminoma or gonadoblastoma had been published so far in the XO-Turner's syndrome. With this report, another case of Turner's syndrome developing a dysgerminoma in a gonadal streak is presented. No Y-chromosome containing stemline could be detected in the patient nor in the tumour. A primary genetic etiology or a mechanism related to early secondary regression or dysgenesis of the gonad are discussed as causative factors in germ cell tumour development within gonadal streaks."} {"id": "PMID:1275867", "title": "[Influence of industrialization on trace element concentration in human lungs].", "content": "People who spend their entire lives in highly industrialized regions are in danger of accumulating trace elements by inhalation as a result of the increased amounts of factory-produced smoke. In order to test the environmentally accumulated trace elements in lungs, lung samples of patients who lived their entire lives in the industrial area of Duisburg were compared with those of patients from the less industrialized areas of Cologne and surroundings. Five patients were studied who lived in Duisburg and died at 50-68 years but not primarily as a result of lung diseases. From each patient five samples of the left lung were removed at autopsy. Lungs from 18 patients who died in Cologne were also examined. From each of the latter 2 samples were removed from the left lung. All samples were studied by means of neutron activation analysis and the following elements analysed: Co, Fe, Rb, Se, Cr, Cs, Sb, Sc, Zn and Al. The Al-concentration was analysed only in patients aged 50-68 years. The values of the non-essential Sc, Al and Cs and of the essential trace elements Co were found to be appreciably higher in the samples from Duisburg than in those from Cologne. Sc in the samples from the highly industrialized area was increased up to a factor of 100, Cs, Al and Co to a factor of 10. In the lungs of adults in Duisburg, aged 50-68 years, the concentration of Sc was more than 1,000 times greater than in lungs of children in Cologne, aged 0-10 years. In all samples from Duisburg, the rare element Eu was detectable by means of neutron activation analysis but could not be detected in a sample from Cologne. It is likely that the different uptakes of trace elements in the lungs depend on correspondingly different concentrations of the elements in the air. The extensive accumulation, especially of the non-essential elements, in the lungs should be an incentive to examine possible detrimental effects on human health in the future. The element Sc which was strikingly accumulated in the lungs and which can be easily measured by neutron activation analysis might be used as a standard for estimating the extent of environmental pollution.", "contents": "[Influence of industrialization on trace element concentration in human lungs]. People who spend their entire lives in highly industrialized regions are in danger of accumulating trace elements by inhalation as a result of the increased amounts of factory-produced smoke. In order to test the environmentally accumulated trace elements in lungs, lung samples of patients who lived their entire lives in the industrial area of Duisburg were compared with those of patients from the less industrialized areas of Cologne and surroundings. Five patients were studied who lived in Duisburg and died at 50-68 years but not primarily as a result of lung diseases. From each patient five samples of the left lung were removed at autopsy. Lungs from 18 patients who died in Cologne were also examined. From each of the latter 2 samples were removed from the left lung. All samples were studied by means of neutron activation analysis and the following elements analysed: Co, Fe, Rb, Se, Cr, Cs, Sb, Sc, Zn and Al. The Al-concentration was analysed only in patients aged 50-68 years. The values of the non-essential Sc, Al and Cs and of the essential trace elements Co were found to be appreciably higher in the samples from Duisburg than in those from Cologne. Sc in the samples from the highly industrialized area was increased up to a factor of 100, Cs, Al and Co to a factor of 10. In the lungs of adults in Duisburg, aged 50-68 years, the concentration of Sc was more than 1,000 times greater than in lungs of children in Cologne, aged 0-10 years. In all samples from Duisburg, the rare element Eu was detectable by means of neutron activation analysis but could not be detected in a sample from Cologne. It is likely that the different uptakes of trace elements in the lungs depend on correspondingly different concentrations of the elements in the air. The extensive accumulation, especially of the non-essential elements, in the lungs should be an incentive to examine possible detrimental effects on human health in the future. The element Sc which was strikingly accumulated in the lungs and which can be easily measured by neutron activation analysis might be used as a standard for estimating the extent of environmental pollution."} {"id": "PMID:1275868", "title": "[Malignant melanoma: depth of invasion and histologic typing].", "content": "In classifying a malignant melanoma Clark et al. (1969) have suggested histologic typing (lentigo maligna-melanoma, superficial spreading melanoma, nodular melanoma) as well as the determination of the depth of invasion. The experiences made so far need further confirmation through respective research in additional material. This applies to the frequency of histologic types of melanoma and the microstages and primarily to the prognostic significance. There appear to be correlations whether the depth of invasion or the type of melanoma is decisive for prognosis or whether both have to be considered. Between 1967 and 1974 the depth of invasion and the type of melanoma were determined according to Clark et al. (1969) in 139 invasive malignant melanomas. This classification has been carried out routinely following the excision of the tumor since Jan 1st, 1973; in previously operated tumors it was carried out in retrospect without knowledge of the follow-up. Without exception multiple sections of several blocks were used. Uncorrected survival curves and survival rates were drawn up using the acturaial method. Results 1. Of 139 malignant melanomas 3 (2%) were found to be in microstage 2, 50 (36%) in microstage 3, 71 (51%) in microstage 4 and is (11%) in microstage 5. 2. The type of 2 melanomas could not be defined. Among the remaining invasive malignant melanomas 17 (12%) were lentigo maligna melanomas, 48 (35%) were superficial spreading melanomas and 72 (53%) nodular melanomas. 3. Of the 72 nodular melanomas 53 (74%) were found in microstage 4 or 5; of the 65 other melanomas (lentigo maligna melanomas or superficial spreading melanomas), however, only 34 (52%) p less than 0,001) were in this stage. 4. The uncorrected 5-year survival rate was 100% in microstage 2 and 3 and in tumours diameter of 0.76 mm or more, 55% in microstage 4 and 31% in microstage 5. 5. At equal depth of invasion there are no significant prognostic differences between the various types of melanomas. It was possible to reproduce the type classification of melanomas as introduced by Clark et al. (1969) in our own material from 139 patients. Tumors of microstage 2 were less frequent in our material (2%) than in American and Australian series (17-28%). As far as the frequency of the types of melanoma and the correlation between the type of melanoma and depth of invasion are concerned, the Erlangen material does not show considerable deviation from the reports in the literature on the subject. Among tumors of equal depth of invasion the type of melanoma has little prognostic impact. The depth of invasion is decisive for the prognosis. It can be determined with little effort to a high degree of reliability.", "contents": "[Malignant melanoma: depth of invasion and histologic typing]. In classifying a malignant melanoma Clark et al. (1969) have suggested histologic typing (lentigo maligna-melanoma, superficial spreading melanoma, nodular melanoma) as well as the determination of the depth of invasion. The experiences made so far need further confirmation through respective research in additional material. This applies to the frequency of histologic types of melanoma and the microstages and primarily to the prognostic significance. There appear to be correlations whether the depth of invasion or the type of melanoma is decisive for prognosis or whether both have to be considered. Between 1967 and 1974 the depth of invasion and the type of melanoma were determined according to Clark et al. (1969) in 139 invasive malignant melanomas. This classification has been carried out routinely following the excision of the tumor since Jan 1st, 1973; in previously operated tumors it was carried out in retrospect without knowledge of the follow-up. Without exception multiple sections of several blocks were used. Uncorrected survival curves and survival rates were drawn up using the acturaial method. Results 1. Of 139 malignant melanomas 3 (2%) were found to be in microstage 2, 50 (36%) in microstage 3, 71 (51%) in microstage 4 and is (11%) in microstage 5. 2. The type of 2 melanomas could not be defined. Among the remaining invasive malignant melanomas 17 (12%) were lentigo maligna melanomas, 48 (35%) were superficial spreading melanomas and 72 (53%) nodular melanomas. 3. Of the 72 nodular melanomas 53 (74%) were found in microstage 4 or 5; of the 65 other melanomas (lentigo maligna melanomas or superficial spreading melanomas), however, only 34 (52%) p less than 0,001) were in this stage. 4. The uncorrected 5-year survival rate was 100% in microstage 2 and 3 and in tumours diameter of 0.76 mm or more, 55% in microstage 4 and 31% in microstage 5. 5. At equal depth of invasion there are no significant prognostic differences between the various types of melanomas. It was possible to reproduce the type classification of melanomas as introduced by Clark et al. (1969) in our own material from 139 patients. Tumors of microstage 2 were less frequent in our material (2%) than in American and Australian series (17-28%). As far as the frequency of the types of melanoma and the correlation between the type of melanoma and depth of invasion are concerned, the Erlangen material does not show considerable deviation from the reports in the literature on the subject. Among tumors of equal depth of invasion the type of melanoma has little prognostic impact. The depth of invasion is decisive for the prognosis. It can be determined with little effort to a high degree of reliability."} {"id": "PMID:1275869", "title": "[Reversible hyperplasia and hypertrophy of the mouse liver induced by a functional charge with phenobarbital].", "content": "Administration of phenobarbital to rats and mice is well known to cause enlargement of the liver, where the drug is metabolized by hydroxylation and oxydation. The increase of the liver weight is thought to be due to and enlargement of the individual hepatocytes (hypertrophy) caused by an augmentation of the smooth endoplasmic reticulum, as well as to cell multiplication (hyperplasia). The present investigation deals with the nuclear DNA content of mouse hepatocytes during and after administration of different doses of phenobarbital. The data are related to liver weight with due consideration of mitotic activity and cell loss by necrobiosis. 172 five to six weeks old male albino NMRI mice with a body weight of 23 to 33 gms were randomly divided into four groups, one of which served as the controls. The three test groups received 75 mg and 150 mg phenobarbital per 1 kg body weight intraperitoneally once every day for a total of 10 days. Thereafter the administration of the drug was discontinued. Beginning with the third day of the experiment 3 animals of each group were sacrificed by exsanguination every secound day after their body weight had been carefully determined. Then the liver weights were measured. The nuclear DNA content of the hepatocytes was determined from liver smears by means of acriflavine-Feulgen fluorescence cytophotometry. The number of mitotic figures and of necrobiotic liver cells was counted in histologic sections. With animals receiving 150 mg and 100 mg phenobarbital per 1 kg body weight a rapid increase of the relative liver weight (up to 74% above the controls) was observed, which was reduced back to normal levels within 10 days after discontinuation of the drug. Parallel with the increase of the liver weight a striking DNA-polyploidisation of the liver nuclei occurred which proved to be reversible during the reduction phase. Mitotic figures were found only in the initial phase of the experiment (third to fifth day), while the number of necrobiotic hepatocytes was increased after the drug was discontinued. Similar but markedly less pronounced effects were encountered with animals of the 75 group. It is concluded that the increase of the liver weight of mice after phenobarbital administration is partly due to cell multiplication (hyperplasia) - as is shown by a high number of mitotic figures in the initial phase of the experiment-, partly due to the enlargement of hepatocytes with concommitant polyploidisation of the muclei (hypertrophy). When the drug administration is discontinued the liver weights return to normal levels within 10 days. Since at the same time the number of high-ploidy nuclei is reduced with no evidence of an increased mitotic activity, the reduction of the liver weight should be partly caused by an elimination of high-ploidy hepatocytes, which are no longer required after the hyperfunctional stimulus has ceased...", "contents": "[Reversible hyperplasia and hypertrophy of the mouse liver induced by a functional charge with phenobarbital]. Administration of phenobarbital to rats and mice is well known to cause enlargement of the liver, where the drug is metabolized by hydroxylation and oxydation. The increase of the liver weight is thought to be due to and enlargement of the individual hepatocytes (hypertrophy) caused by an augmentation of the smooth endoplasmic reticulum, as well as to cell multiplication (hyperplasia). The present investigation deals with the nuclear DNA content of mouse hepatocytes during and after administration of different doses of phenobarbital. The data are related to liver weight with due consideration of mitotic activity and cell loss by necrobiosis. 172 five to six weeks old male albino NMRI mice with a body weight of 23 to 33 gms were randomly divided into four groups, one of which served as the controls. The three test groups received 75 mg and 150 mg phenobarbital per 1 kg body weight intraperitoneally once every day for a total of 10 days. Thereafter the administration of the drug was discontinued. Beginning with the third day of the experiment 3 animals of each group were sacrificed by exsanguination every secound day after their body weight had been carefully determined. Then the liver weights were measured. The nuclear DNA content of the hepatocytes was determined from liver smears by means of acriflavine-Feulgen fluorescence cytophotometry. The number of mitotic figures and of necrobiotic liver cells was counted in histologic sections. With animals receiving 150 mg and 100 mg phenobarbital per 1 kg body weight a rapid increase of the relative liver weight (up to 74% above the controls) was observed, which was reduced back to normal levels within 10 days after discontinuation of the drug. Parallel with the increase of the liver weight a striking DNA-polyploidisation of the liver nuclei occurred which proved to be reversible during the reduction phase. Mitotic figures were found only in the initial phase of the experiment (third to fifth day), while the number of necrobiotic hepatocytes was increased after the drug was discontinued. Similar but markedly less pronounced effects were encountered with animals of the 75 group. It is concluded that the increase of the liver weight of mice after phenobarbital administration is partly due to cell multiplication (hyperplasia) - as is shown by a high number of mitotic figures in the initial phase of the experiment-, partly due to the enlargement of hepatocytes with concommitant polyploidisation of the muclei (hypertrophy). When the drug administration is discontinued the liver weights return to normal levels within 10 days. Since at the same time the number of high-ploidy nuclei is reduced with no evidence of an increased mitotic activity, the reduction of the liver weight should be partly caused by an elimination of high-ploidy hepatocytes, which are no longer required after the hyperfunctional stimulus has ceased..."} {"id": "PMID:1275882", "title": "Properties of the testicular lactate dehydrogenase isoenzyme.", "content": "1. Studies were carried out with pure lactate dehydrogenase isoenzymes C4 (LDH isoenzyme X), B4, (LDH isoenzyme 1) and A4 (LDH isoenzyme 5) isolated from mouse testis, heart and muscle tissue respectively; with LDH isoenzyme X purified from pigeon testes and with crude lysates of spermatozoa from man, bull and rabbit. 2. LDH isoenzyme X from all species showed greater ability than the other isoenzymes to catalyse the NAD+-linked interconversions of 2-oxobutanoate into 2-hydroxybutanoate and of 2-oxopentanoate into 2-hydroxypentanoate. 3. Mouse LDH isoenzyme X presented the broadest spectrum of substrate specificity. It exhibited very similar Km values for a variety of 2-oxo acids: 2-oxopropanoate (pyruvate), 2-oxobutanoate, 2-oxo-3-methylbutanoate, 2-oxopentanoate, 2-oxo-3-methylpentanoate, 2-oxo-4-methylpentanoate, 2-oxohexanoate and 2-oxo-3-phenylpropanoate (phenylpyruvate). The corresponding 2-hydroxy acids were also readily utilized in the reverse reaction. A strong inhibition by substrate and product was demonstrated for the direct reaction. 4. Intracellular distribution of LDH isoenzyme X was investigated in mouse testes. LDH isoenzyme X activity was located in the fraction of \"heavy mitochondria\" and in the soluble phase. 5. A possible functional role for LDH isoenzyme X is proposed: the redox couple-2-oxo acid-2-hydroxy acid could integrate a shuttle system transferring reducing equivalents from cytoplasm to mitochondria.", "contents": "Properties of the testicular lactate dehydrogenase isoenzyme. 1. Studies were carried out with pure lactate dehydrogenase isoenzymes C4 (LDH isoenzyme X), B4, (LDH isoenzyme 1) and A4 (LDH isoenzyme 5) isolated from mouse testis, heart and muscle tissue respectively; with LDH isoenzyme X purified from pigeon testes and with crude lysates of spermatozoa from man, bull and rabbit. 2. LDH isoenzyme X from all species showed greater ability than the other isoenzymes to catalyse the NAD+-linked interconversions of 2-oxobutanoate into 2-hydroxybutanoate and of 2-oxopentanoate into 2-hydroxypentanoate. 3. Mouse LDH isoenzyme X presented the broadest spectrum of substrate specificity. It exhibited very similar Km values for a variety of 2-oxo acids: 2-oxopropanoate (pyruvate), 2-oxobutanoate, 2-oxo-3-methylbutanoate, 2-oxopentanoate, 2-oxo-3-methylpentanoate, 2-oxo-4-methylpentanoate, 2-oxohexanoate and 2-oxo-3-phenylpropanoate (phenylpyruvate). The corresponding 2-hydroxy acids were also readily utilized in the reverse reaction. A strong inhibition by substrate and product was demonstrated for the direct reaction. 4. Intracellular distribution of LDH isoenzyme X was investigated in mouse testes. LDH isoenzyme X activity was located in the fraction of \"heavy mitochondria\" and in the soluble phase. 5. A possible functional role for LDH isoenzyme X is proposed: the redox couple-2-oxo acid-2-hydroxy acid could integrate a shuttle system transferring reducing equivalents from cytoplasm to mitochondria."} {"id": "PMID:1275883", "title": "Chemical nature and sequence of alamethicin.", "content": "An n.m.r. spectroscopy study of pure alamethicin shows it to be a linear polypeptide of 19 residues. The N-terminus is blocked by an acetyl group, and the eighteenth residue, glutamic acid, is linked by an amide bond on its side chain to phenylalaninol (Fig. 6). The new formula is confirmed by a comparison between pure chemical compounds and the products of partial hydrolysis.", "contents": "Chemical nature and sequence of alamethicin. An n.m.r. spectroscopy study of pure alamethicin shows it to be a linear polypeptide of 19 residues. The N-terminus is blocked by an acetyl group, and the eighteenth residue, glutamic acid, is linked by an amide bond on its side chain to phenylalaninol (Fig. 6). The new formula is confirmed by a comparison between pure chemical compounds and the products of partial hydrolysis."} {"id": "PMID:1275884", "title": "Mobility of sodium dodecyl sulphate - protein complexes.", "content": "Reduced and unreduced lysozyme aggregates formed by formaldehyde cross-linking comprise a set of model compounds for studying the effects of protein conformation on the electrophoretic mobilities of sodium dodecyl sulphate-protein complexes. The reduced aggregates were indistinguisable from normal proteins, but the unreduced aggregates migrated anomalously fast by about 14%. Contrary to expectations, plots of logarithm Rf versus Kr (retardation coefficient) failed to reveal an unusual conformation for the unreduced aggregates. Thus the anomalous mobility caused by several intramolecular disulphide bonds escaped detection by the above two diagnostic plots. Also included in this paper is a discussion of the implications of these results with regard to current models for sodium dodecyl sulphate-protein complexes.", "contents": "Mobility of sodium dodecyl sulphate - protein complexes. Reduced and unreduced lysozyme aggregates formed by formaldehyde cross-linking comprise a set of model compounds for studying the effects of protein conformation on the electrophoretic mobilities of sodium dodecyl sulphate-protein complexes. The reduced aggregates were indistinguisable from normal proteins, but the unreduced aggregates migrated anomalously fast by about 14%. Contrary to expectations, plots of logarithm Rf versus Kr (retardation coefficient) failed to reveal an unusual conformation for the unreduced aggregates. Thus the anomalous mobility caused by several intramolecular disulphide bonds escaped detection by the above two diagnostic plots. Also included in this paper is a discussion of the implications of these results with regard to current models for sodium dodecyl sulphate-protein complexes."} {"id": "PMID:1275885", "title": "Preparation and activity of guanidinated or acetylated erabutoxins.", "content": "1. Erabutoxins, a, b and c, neurotoxic proteins of a sea snake Lacticauda semifasciata, were guanidinated with O-methylisourea. The amino groups of all the lysine residues and those at the N-termini of the toxins were modified. The lethal activity of the toxins decreased to 50% (erabutoxins a and b) or 17% (erabutoxin c) of the original value on the modification. The c.d. (circular dichroism) maximum at 227 nm of the modified toxins became lower, whereas the whole profile of the c.d. curve remained unchanged. 2. The amino groups of erabutoxin b were acetylated with acetic anhydride. All the five monoacetyl derivatives were isolated from the reaction products by CM-cellulose and Bio-Rex 70 column chromatography. [1-Nalpha-acetylarginine]-, [15-N6-acetyl-lysine]- and [51-N6-acetyl-lysine]-erabutoxin b retained the toxicity of the native toxin, whereas [27-N6-acetyl-lysine] and [47-N6-acetyl-lysine]-erabutoxin b were 17 and 8% active respectively. The overall profile of c.d. spectrum of erabutoxin b remained unchanged on the monoacetylation.", "contents": "Preparation and activity of guanidinated or acetylated erabutoxins. 1. Erabutoxins, a, b and c, neurotoxic proteins of a sea snake Lacticauda semifasciata, were guanidinated with O-methylisourea. The amino groups of all the lysine residues and those at the N-termini of the toxins were modified. The lethal activity of the toxins decreased to 50% (erabutoxins a and b) or 17% (erabutoxin c) of the original value on the modification. The c.d. (circular dichroism) maximum at 227 nm of the modified toxins became lower, whereas the whole profile of the c.d. curve remained unchanged. 2. The amino groups of erabutoxin b were acetylated with acetic anhydride. All the five monoacetyl derivatives were isolated from the reaction products by CM-cellulose and Bio-Rex 70 column chromatography. [1-Nalpha-acetylarginine]-, [15-N6-acetyl-lysine]- and [51-N6-acetyl-lysine]-erabutoxin b retained the toxicity of the native toxin, whereas [27-N6-acetyl-lysine] and [47-N6-acetyl-lysine]-erabutoxin b were 17 and 8% active respectively. The overall profile of c.d. spectrum of erabutoxin b remained unchanged on the monoacetylation."} {"id": "PMID:1275886", "title": "Triterpenoid carotenoids and related lipids. Triterpenoid carotenoid aldehydes from Streptococcus faecium UNH 564P.", "content": "1. The identification of two novel triterpenoid xanthophylls from Streptococcus faecium UNH 564P is described. 2. Both are aldehydes and were identified as 4,4'-diaponeurosporen-4-al and 4,4'-diapolycopen-4-al. 3. A pathway is presented for the biosynthesis of these and other triterpenoid carotenoids in S. faecium.", "contents": "Triterpenoid carotenoids and related lipids. Triterpenoid carotenoid aldehydes from Streptococcus faecium UNH 564P. 1. The identification of two novel triterpenoid xanthophylls from Streptococcus faecium UNH 564P is described. 2. Both are aldehydes and were identified as 4,4'-diaponeurosporen-4-al and 4,4'-diapolycopen-4-al. 3. A pathway is presented for the biosynthesis of these and other triterpenoid carotenoids in S. faecium."} {"id": "PMID:1275887", "title": "The theory of the deoxyribonucleic acid - ribonucleic acid hybridization reaction.", "content": "A general equation is derived describing data of DNA-RNA hybridization in the presence of a competing self-annealing reaction of RNA. The well known double-reciprocal relation and the Scatchard equation are shown to be limiting cases of this general equation. Some new hybridization data at various temperatures are presented and analysed by using the new equation. The results can only be explained if we assume that the behavior of DNA towards single RNA molecules is the same as that towards the annealed form, (RNA12. The variation of the equilibrium constant of the hybridization reaction with temperature is small, indicating a small heat of reaction. The maximum amount of hybridized RNA at equilibrium appears to be independent of temperature.", "contents": "The theory of the deoxyribonucleic acid - ribonucleic acid hybridization reaction. A general equation is derived describing data of DNA-RNA hybridization in the presence of a competing self-annealing reaction of RNA. The well known double-reciprocal relation and the Scatchard equation are shown to be limiting cases of this general equation. Some new hybridization data at various temperatures are presented and analysed by using the new equation. The results can only be explained if we assume that the behavior of DNA towards single RNA molecules is the same as that towards the annealed form, (RNA12. The variation of the equilibrium constant of the hybridization reaction with temperature is small, indicating a small heat of reaction. The maximum amount of hybridized RNA at equilibrium appears to be independent of temperature."} {"id": "PMID:1275888", "title": "A new subunit of horse liver alcohol dehydrogenase and subunit composition of the polymorphic form.", "content": "The most cathodal (on starch-gel electrophoresis), steroid-active band of horse liver alcohol dehydrogenase, whose catalytic properties were shown to be dependent on the livers used as a starting material [Pietruszko (1974) Biochem. Biophys. Res. Commun. 60, 687-694], has been prepared from A-type and S-type horse livers by identical methods. Results presented here show that different isoenzymes are present in these preparations.", "contents": "A new subunit of horse liver alcohol dehydrogenase and subunit composition of the polymorphic form. The most cathodal (on starch-gel electrophoresis), steroid-active band of horse liver alcohol dehydrogenase, whose catalytic properties were shown to be dependent on the livers used as a starting material [Pietruszko (1974) Biochem. Biophys. Res. Commun. 60, 687-694], has been prepared from A-type and S-type horse livers by identical methods. Results presented here show that different isoenzymes are present in these preparations."} {"id": "PMID:1275889", "title": "A method for the direct demonstration of the lectin-binding components of the human erythrocyte membrane.", "content": "1. A method which allows the characterization of lectin-binding components is described. This method should be useful in defining the nature and heterogeneity of these components in cell membranes. 2. The method, which we have used on erythrocyte \"ghosts\", involves the fixation of \"ghost\" components after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and incubation with purified 125I-labelled lectins. 3. Each of the four lectins used shows an individual pattern of reactivity towards \"ghosts\" components. Band 3, the major membrane-penetrating glycoprotein, is bound by the lectins from Ricinus communis and Phaseolus vulgaris (phytohaemagglutinin) and by concanavalin A. The major erythrocyte sialoglycoprotein is bound by the lectins from R. communis, P. vulgaris and Maclura aurantiaca. 4. Three of the lectins displays binding for other membrane components, some of which are not demonstratable by conventional protein- and carbohydrate-staining techniques.", "contents": "A method for the direct demonstration of the lectin-binding components of the human erythrocyte membrane. 1. A method which allows the characterization of lectin-binding components is described. This method should be useful in defining the nature and heterogeneity of these components in cell membranes. 2. The method, which we have used on erythrocyte \"ghosts\", involves the fixation of \"ghost\" components after sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and incubation with purified 125I-labelled lectins. 3. Each of the four lectins used shows an individual pattern of reactivity towards \"ghosts\" components. Band 3, the major membrane-penetrating glycoprotein, is bound by the lectins from Ricinus communis and Phaseolus vulgaris (phytohaemagglutinin) and by concanavalin A. The major erythrocyte sialoglycoprotein is bound by the lectins from R. communis, P. vulgaris and Maclura aurantiaca. 4. Three of the lectins displays binding for other membrane components, some of which are not demonstratable by conventional protein- and carbohydrate-staining techniques."} {"id": "PMID:1275890", "title": "The membrane change in En(a-) human erythrocytes. Absence of the major erythrocyte sialoglycoprotein.", "content": "We investigated the membrane of En(a-) human erythrocytes as part of a study of the structure and biochemical function of the surface glycoproteins of the mammalian cell. 2. En(a-) erythrocytes were selected because they have more extensive changes at the cell surface than any other known erythrocyte variant. 3. Our results show that in En(a-) erythrocytes: (a) the major membrane sialoglycoprotein is lacking; (b) the other major membrane-penetrating glycoprotein (band 3) has an altered electrophoretic mobility. 4. The apparent clinical normality of En(a-) cells suggests that the change in band 3 may compensate for the loss of the membrane sialoglycoproteins. It is clear that a viable erythrocyte can exist despite the absence of one of its major surface components.", "contents": "The membrane change in En(a-) human erythrocytes. Absence of the major erythrocyte sialoglycoprotein. We investigated the membrane of En(a-) human erythrocytes as part of a study of the structure and biochemical function of the surface glycoproteins of the mammalian cell. 2. En(a-) erythrocytes were selected because they have more extensive changes at the cell surface than any other known erythrocyte variant. 3. Our results show that in En(a-) erythrocytes: (a) the major membrane sialoglycoprotein is lacking; (b) the other major membrane-penetrating glycoprotein (band 3) has an altered electrophoretic mobility. 4. The apparent clinical normality of En(a-) cells suggests that the change in band 3 may compensate for the loss of the membrane sialoglycoproteins. It is clear that a viable erythrocyte can exist despite the absence of one of its major surface components."} {"id": "PMID:1275891", "title": "Further evidence for an allosteric model for ribonuclease.", "content": "Evidence is presented from three experimental systems to support the allosteric model of Walker et al. (1975) (Biochem. J. 147, 425-433) which explains the substrate-concentration-dependent transition observed in the RNAase (ribonuclease)-catalysed hydrolysis of 2':3'-cyclic CMP (cytidine 2':3'-cyclic monophosphate). 1. Kinetic studies of the initial rate of hydrolysis of 2':3'-cyclic CMP show that the midpoint of the transition shifts to lower concentrations of 2':3'-cyclic CMP in the presence of the substrate analogues 3'-CMP, 5'-CMP, 3'-AMP, 3'-UMP and Pi; 2'-CMP and 2'-UMP do not cause such a shift. 2. Trypsin-digestion studies show that a conformational change in RNAase to a form less susceptible to tryptic inactivation is induced in the presence of the substrate analogues 3'-CMP, 5'-CMP, 3'-AMP, and 3'-UMP. 2'-CMP, 2'-AMP and 2'-UMP do not induce this conformational change. 3. Equilibrium-dialysis experiments demonstrate the multiple binding of molecules of 3'-CMP, 3'-AMP and 5'-AMP to a molecule of RNAase. 2'-CMP binds the ratio 1:1 over the analogue concentration range studied.", "contents": "Further evidence for an allosteric model for ribonuclease. Evidence is presented from three experimental systems to support the allosteric model of Walker et al. (1975) (Biochem. J. 147, 425-433) which explains the substrate-concentration-dependent transition observed in the RNAase (ribonuclease)-catalysed hydrolysis of 2':3'-cyclic CMP (cytidine 2':3'-cyclic monophosphate). 1. Kinetic studies of the initial rate of hydrolysis of 2':3'-cyclic CMP show that the midpoint of the transition shifts to lower concentrations of 2':3'-cyclic CMP in the presence of the substrate analogues 3'-CMP, 5'-CMP, 3'-AMP, 3'-UMP and Pi; 2'-CMP and 2'-UMP do not cause such a shift. 2. Trypsin-digestion studies show that a conformational change in RNAase to a form less susceptible to tryptic inactivation is induced in the presence of the substrate analogues 3'-CMP, 5'-CMP, 3'-AMP, and 3'-UMP. 2'-CMP, 2'-AMP and 2'-UMP do not induce this conformational change. 3. Equilibrium-dialysis experiments demonstrate the multiple binding of molecules of 3'-CMP, 3'-AMP and 5'-AMP to a molecule of RNAase. 2'-CMP binds the ratio 1:1 over the analogue concentration range studied."} {"id": "PMID:1275892", "title": "Beta-amylase-resistant amylose. Effect of urea on the limited hydrolysis of amylose by beta-amylase.", "content": "Amylose prepared from starch dispersed in 10M-urea, pH6.2, was found to be resistant to the action of beta-amylase and phosphorylase, though it was degraded by alpha-amylase. Amylose isolated by conventional methods was similarly refractory after urea treatment, and was hydrolysed by beta-amylase to the extent of 32-35%; it had no inhibitory effect towards beta-amylase. The physical and chemical properties of the modified amylose were in general comparable with those of normal amylose with a beta-amylolysis limit of 94-98%. Starch and amylopectin were unaffected by urea treatment, i.e. the presence of amylopectin protected amylose against changes induced in it by urea. It is speculated that urea treatment \"freezes\" amylose molecules in a conformation that renders non-reducing termini inaccessible to the active site of the exo-enzymes. Such changes may limit the degradative action of beta-amylase and phosphorylase.", "contents": "Beta-amylase-resistant amylose. Effect of urea on the limited hydrolysis of amylose by beta-amylase. Amylose prepared from starch dispersed in 10M-urea, pH6.2, was found to be resistant to the action of beta-amylase and phosphorylase, though it was degraded by alpha-amylase. Amylose isolated by conventional methods was similarly refractory after urea treatment, and was hydrolysed by beta-amylase to the extent of 32-35%; it had no inhibitory effect towards beta-amylase. The physical and chemical properties of the modified amylose were in general comparable with those of normal amylose with a beta-amylolysis limit of 94-98%. Starch and amylopectin were unaffected by urea treatment, i.e. the presence of amylopectin protected amylose against changes induced in it by urea. It is speculated that urea treatment \"freezes\" amylose molecules in a conformation that renders non-reducing termini inaccessible to the active site of the exo-enzymes. Such changes may limit the degradative action of beta-amylase and phosphorylase."} {"id": "PMID:1275893", "title": "Studies on the use of sepharose-N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucopyranose for the large-scale purification of hepatic glucokinase.", "content": "The synthesis of N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucose is described and it was shown to be a competitive inhibitor (Ki, 0.75 mM) with respect to glucose of rat hepatic glucokinase (EC 2.7.1.2). After attachment to CNBr-activated Sepharose 4B, this derivative was able to remove glucokinase quantitatively from crude liver extracts and release it when the columns were developed with glucose, glucosamine, N-acetyl-glucosamine or KC1. Repeated exposure of the columns to liver extracts led to rapid loss in their effectiveness as affinity matrices because proteins other than glucokinase are bound to the columns. The nature of such protein binding and methods for the rejuvenation of \"used\" columns are discussed along with the effect of the mode of preparation of the Sepharose-ligand conjugate and the concentration of bound ligand on the purification of glucokinase. Glucose 6-phosphate dehydrogenase is cited as an example of both non-specific protein binding to the affinity column and of the importance of the control of ligand concentration in removing such non-specifically bound proteins. Some guidelines emerged that should be generally applicable to other systems, particularly those which involve affinity chromatography of enzymes that are present in tissue extracts in very low amounts and possess only a relatively low association constant for the immobilized ligand.", "contents": "Studies on the use of sepharose-N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucopyranose for the large-scale purification of hepatic glucokinase. The synthesis of N-(6-aminohexanoyl)-2-amino-2-deoxy-D-glucose is described and it was shown to be a competitive inhibitor (Ki, 0.75 mM) with respect to glucose of rat hepatic glucokinase (EC 2.7.1.2). After attachment to CNBr-activated Sepharose 4B, this derivative was able to remove glucokinase quantitatively from crude liver extracts and release it when the columns were developed with glucose, glucosamine, N-acetyl-glucosamine or KC1. Repeated exposure of the columns to liver extracts led to rapid loss in their effectiveness as affinity matrices because proteins other than glucokinase are bound to the columns. The nature of such protein binding and methods for the rejuvenation of \"used\" columns are discussed along with the effect of the mode of preparation of the Sepharose-ligand conjugate and the concentration of bound ligand on the purification of glucokinase. Glucose 6-phosphate dehydrogenase is cited as an example of both non-specific protein binding to the affinity column and of the importance of the control of ligand concentration in removing such non-specifically bound proteins. Some guidelines emerged that should be generally applicable to other systems, particularly those which involve affinity chromatography of enzymes that are present in tissue extracts in very low amounts and possess only a relatively low association constant for the immobilized ligand."} {"id": "PMID:1275894", "title": "The purification in high yield and characterization of rat hepatic glucokinase.", "content": "A new improved procedure for the purification of rat hepatic glucokinase (ATP-d-glucose 6-phosphotransferase, EC 2.7.1.2) is given. A key step is affinity chromatography on Sepharose-N-(6-aminohexanoyl)-2-amino-2-deoxy-d-glucopyranose. A homogeneous enzyme, specific activity 150 units/mg of protein, is obtained in about 40% yield. The molecular weight of the pure enzyme was determined by several procedures. In particular, sedimentation-equilibrium studies under a variety of conditions indicate a molecular weight of 48000 and no evidence for dimerization; reports in the literature of other values are discussed in the light of this evidence on the pure enzyme. The amino acid composition suggests that hepatic glucokinase is closely related to rat brain hexokinase and also the wheat \"light\" hexokinases.", "contents": "The purification in high yield and characterization of rat hepatic glucokinase. A new improved procedure for the purification of rat hepatic glucokinase (ATP-d-glucose 6-phosphotransferase, EC 2.7.1.2) is given. A key step is affinity chromatography on Sepharose-N-(6-aminohexanoyl)-2-amino-2-deoxy-d-glucopyranose. A homogeneous enzyme, specific activity 150 units/mg of protein, is obtained in about 40% yield. The molecular weight of the pure enzyme was determined by several procedures. In particular, sedimentation-equilibrium studies under a variety of conditions indicate a molecular weight of 48000 and no evidence for dimerization; reports in the literature of other values are discussed in the light of this evidence on the pure enzyme. The amino acid composition suggests that hepatic glucokinase is closely related to rat brain hexokinase and also the wheat \"light\" hexokinases."} {"id": "PMID:1275895", "title": "A study of the supposed hydroxylation of tyrosine catalysed by peroxidase.", "content": "The claim that peroxidase (rather than tyrosinase) is the enzyme responsible for the conversion of tyrosine into dopa (3,4-dihydroxyphenylalanine) in melanogenesis was investigated. The spectral changes that occurred during the action of horseradish peroxidase in the presence of H2O2 on dopa, tyrosine and mixtures of dopa with tyrosine or other phenolic compounds were studied. The effect of ascorbic acid or dihydroxyfumaric acid on some of these changes was also investigated. No evidence was found that tyrosine was hydroxylated by peroxidase in the presence of H2O2 and dopa as cofactor, although tyrosine or other phenolic compounds increased the rate of oxidation of dopa to dopachrome (indoline-5,6-quinone-2-carboxylic acid). Peroxidase was, however, effective in oxidizing tyrosine to dopa in the presence of dihydroxyfumaric acid and oxygen.", "contents": "A study of the supposed hydroxylation of tyrosine catalysed by peroxidase. The claim that peroxidase (rather than tyrosinase) is the enzyme responsible for the conversion of tyrosine into dopa (3,4-dihydroxyphenylalanine) in melanogenesis was investigated. The spectral changes that occurred during the action of horseradish peroxidase in the presence of H2O2 on dopa, tyrosine and mixtures of dopa with tyrosine or other phenolic compounds were studied. The effect of ascorbic acid or dihydroxyfumaric acid on some of these changes was also investigated. No evidence was found that tyrosine was hydroxylated by peroxidase in the presence of H2O2 and dopa as cofactor, although tyrosine or other phenolic compounds increased the rate of oxidation of dopa to dopachrome (indoline-5,6-quinone-2-carboxylic acid). Peroxidase was, however, effective in oxidizing tyrosine to dopa in the presence of dihydroxyfumaric acid and oxygen."} {"id": "PMID:1275896", "title": "Purification and properties of a kininogenin from the venom of Vipera ammodytes ammodytes.", "content": "A kininogenin (EC 3.4.21.8) was purified from the venom of Vipera ammodytes ammodytes (European sand viper) by a combination of gel filtration and ion-exchange chromatography. The enzyme is approximately six times more active than bovine trypsin in its ability to release vasoactive peptides from a plasma precursor. The kininogenin is a glycoprotein containing 18-20% by weight of carbohydrate. It showed a mol. wt. of 40500 on gel filtration. Gel electrophoresis of the reduced sample in the presence of sodium dodecyl sulphate and 2-mercaptoethanol revealed the presence of two major components of mol.wt. 34300 and 31300. The heterogeneity, which was also observed on disc electrophoresis, was removed by incubation with neuraminidase. After incubation with neuraminidase the kininogenin retained full enzymic activity and possessed an isoelectric point of pH7.2. The carbohydrate content has been decreased to 10% by weight, and the single component seen on electrophoresis in the presence of sodium dodecyl sulphate and 2-mercaptoethanol corresponded to a mol.wt. of 29500.", "contents": "Purification and properties of a kininogenin from the venom of Vipera ammodytes ammodytes. A kininogenin (EC 3.4.21.8) was purified from the venom of Vipera ammodytes ammodytes (European sand viper) by a combination of gel filtration and ion-exchange chromatography. The enzyme is approximately six times more active than bovine trypsin in its ability to release vasoactive peptides from a plasma precursor. The kininogenin is a glycoprotein containing 18-20% by weight of carbohydrate. It showed a mol. wt. of 40500 on gel filtration. Gel electrophoresis of the reduced sample in the presence of sodium dodecyl sulphate and 2-mercaptoethanol revealed the presence of two major components of mol.wt. 34300 and 31300. The heterogeneity, which was also observed on disc electrophoresis, was removed by incubation with neuraminidase. After incubation with neuraminidase the kininogenin retained full enzymic activity and possessed an isoelectric point of pH7.2. The carbohydrate content has been decreased to 10% by weight, and the single component seen on electrophoresis in the presence of sodium dodecyl sulphate and 2-mercaptoethanol corresponded to a mol.wt. of 29500."} {"id": "PMID:1275897", "title": "The heterogeneity of arginases in rat tissues.", "content": "Arginase reactions in rat tissues were shown to be catalysed by three isoenzymes which can be separated by bidirectional electrophoresis on polyacrylamide gels. Anodic electrophoresis reveals a migrating band (isoenzyme I) present in all-non-hepatic tissues except submaxillary gland and a non-migrating band found in all tissues. The latter is resolved by cathodic electrophoresis into isoenzymes III (characteristic of liver and submaxillary gland) and a non-moving band (isoenzyme II), present in kidney, intestine and pancreas. Sequential electrophoresis, in the two directions, of mixture of liver and kidney extracts in the same gel columns separated all three isoenzymes. Differences in the solubilization properties, heat-sensitivity and substrate specificity of arginases from different tissues could be correlated with their electrophoretic behaviour. L-Canavanine could replace arginine as substrate in extracts of kidney but not of liver. Both kidney isoenzymes hydrolysed L-canavanine equally well, whereas isoenzyme III from submaxillary gland showed only very low activity. Antiserum against liver arginase interacted with the enzyme with submaxillary gland, but did not inactivate or adsorb arginase from kidney, intestine or pancreas. The distribution of arginase among 16 normal adult rat tissues is presented; the improved, sensitive, assay method was applicable to tissues containing as little as 0.1% of the hepatic activity.", "contents": "The heterogeneity of arginases in rat tissues. Arginase reactions in rat tissues were shown to be catalysed by three isoenzymes which can be separated by bidirectional electrophoresis on polyacrylamide gels. Anodic electrophoresis reveals a migrating band (isoenzyme I) present in all-non-hepatic tissues except submaxillary gland and a non-migrating band found in all tissues. The latter is resolved by cathodic electrophoresis into isoenzymes III (characteristic of liver and submaxillary gland) and a non-moving band (isoenzyme II), present in kidney, intestine and pancreas. Sequential electrophoresis, in the two directions, of mixture of liver and kidney extracts in the same gel columns separated all three isoenzymes. Differences in the solubilization properties, heat-sensitivity and substrate specificity of arginases from different tissues could be correlated with their electrophoretic behaviour. L-Canavanine could replace arginine as substrate in extracts of kidney but not of liver. Both kidney isoenzymes hydrolysed L-canavanine equally well, whereas isoenzyme III from submaxillary gland showed only very low activity. Antiserum against liver arginase interacted with the enzyme with submaxillary gland, but did not inactivate or adsorb arginase from kidney, intestine or pancreas. The distribution of arginase among 16 normal adult rat tissues is presented; the improved, sensitive, assay method was applicable to tissues containing as little as 0.1% of the hepatic activity."} {"id": "PMID:1275898", "title": "The structure of haem in pyridine/water mixtures and its implication in studies of haem catabolism.", "content": "1. A study of haem spectra in pyridine/water mixtures at low pyridine concentrations revealed changes in haemochrome structure consistent with an aggregation process. No corresponding change in the structure of the haemichrome species was observed. 2. This aggregation has been correlated with a previously observed sharp decrease in the rate of coupled oxidation (degradation) of haem as pyridine concentration is decreased. The decrease appears to be due primarily to haem aggregation and not to changes in the hydrophobic nature of the solvent. The effect of ethanol and butanone addition was examined and supports this conclusion. 3. Evidence is presented that coupled oxidation occurs via the iron (II) species (haemochrome).", "contents": "The structure of haem in pyridine/water mixtures and its implication in studies of haem catabolism. 1. A study of haem spectra in pyridine/water mixtures at low pyridine concentrations revealed changes in haemochrome structure consistent with an aggregation process. No corresponding change in the structure of the haemichrome species was observed. 2. This aggregation has been correlated with a previously observed sharp decrease in the rate of coupled oxidation (degradation) of haem as pyridine concentration is decreased. The decrease appears to be due primarily to haem aggregation and not to changes in the hydrophobic nature of the solvent. The effect of ethanol and butanone addition was examined and supports this conclusion. 3. Evidence is presented that coupled oxidation occurs via the iron (II) species (haemochrome)."} {"id": "PMID:1275899", "title": "Chiral recognition of prochiral centres and general acid-base catalysis. Necessarily interrelated manifestations of active-site structure.", "content": "On the basis of Ogston's [(1948) Nature (London) 162, 963] argument, the following conclusions are indicated by the stereochemistry of the reversible oxidation of glycollate by lactate dehydrogenase: (1) general acid-base catalysis is involved in the reaction; (2) the transformation of enzyme-bound (tetrahedral) substrate into enzyme-bound (trigonal) product involves a conformational transition of the enzyme-coenzyme complex.", "contents": "Chiral recognition of prochiral centres and general acid-base catalysis. Necessarily interrelated manifestations of active-site structure. On the basis of Ogston's [(1948) Nature (London) 162, 963] argument, the following conclusions are indicated by the stereochemistry of the reversible oxidation of glycollate by lactate dehydrogenase: (1) general acid-base catalysis is involved in the reaction; (2) the transformation of enzyme-bound (tetrahedral) substrate into enzyme-bound (trigonal) product involves a conformational transition of the enzyme-coenzyme complex."} {"id": "PMID:1275900", "title": "Activities of citrate synthase and other enzymes of Acetobacter xylinum in situ and in vitro.", "content": "The activities of a number of enzymes, extracted from Acetobacter xylinum, that are involved in carbohydrate metabolism may be accounted for in situ in permeabilized cells. The kinetic properties of citrate synthase and glycerokinase observed in vitro are also retained in situ. So is the regulatory sensitivity of these enzymes. Both in vitro and in situ, (a) citrate synthase, in contrast with the enzyme for other Gram-negative bacteria, is inhibited by ATP and is insensitive to NADH, and (b) glycerokinase is inhibited by fructose diphosphate and the ratio of its activities towards glycerol and dihydroxyacetone is the same.", "contents": "Activities of citrate synthase and other enzymes of Acetobacter xylinum in situ and in vitro. The activities of a number of enzymes, extracted from Acetobacter xylinum, that are involved in carbohydrate metabolism may be accounted for in situ in permeabilized cells. The kinetic properties of citrate synthase and glycerokinase observed in vitro are also retained in situ. So is the regulatory sensitivity of these enzymes. Both in vitro and in situ, (a) citrate synthase, in contrast with the enzyme for other Gram-negative bacteria, is inhibited by ATP and is insensitive to NADH, and (b) glycerokinase is inhibited by fructose diphosphate and the ratio of its activities towards glycerol and dihydroxyacetone is the same."} {"id": "PMID:1275901", "title": "Artifacts in the centrifugation of ribosomal and heterogenous ribonucleic acid in \"99%-dimethyl sulphoxide\" gradients.", "content": "Increasing the total quantity of RNA located on 99%-dimethyl sulphoxide gradients profoundly altered the sedimentation pattern of heterogenous RNA and (to a smaller extent) that of rRNA. Aggregation of small quantities of rRNA with fast-sedimenting heterogenous RNA was also found to occur in these gradients.", "contents": "Artifacts in the centrifugation of ribosomal and heterogenous ribonucleic acid in \"99%-dimethyl sulphoxide\" gradients. Increasing the total quantity of RNA located on 99%-dimethyl sulphoxide gradients profoundly altered the sedimentation pattern of heterogenous RNA and (to a smaller extent) that of rRNA. Aggregation of small quantities of rRNA with fast-sedimenting heterogenous RNA was also found to occur in these gradients."} {"id": "PMID:1275902", "title": "The metabolism of the phosphonium analogue of choline in cultured cells. A useful nuclear-magnetic-resonance probe for membrane phosphatidylcholine.", "content": "1. Replacement of choline by the phosphonium analogue does not affect the growth rate of P815Y, NIL, 3T3, and SV40/3T3 cells in culture. 2. The fatty acid composition of the resulting phosphonium phosphatidylcholine is similar to that of phosphatidylcholine. 3. The rate of synthesis and degradation of phosphatidylcholine and of the phosphonium analogue are similar. 4. Phospholipid-exchange protein does not distinguish between phosphatidylcholine and the phosphonium analogue. 5. By contrast, incorporation of phosphonium choline into sphingomyelin occurs to only a minor extent. 6. It is concluded that, since the enzymes involved in the turnover of phosphatidylcholine do not discriminate between quaternary N and quaternary P in the polar head-group region, phosphonium choline should prove to be a useful probe for 31P nuclear-magnetic-resonance (n.m.r.) studies of natural membranes.", "contents": "The metabolism of the phosphonium analogue of choline in cultured cells. A useful nuclear-magnetic-resonance probe for membrane phosphatidylcholine. 1. Replacement of choline by the phosphonium analogue does not affect the growth rate of P815Y, NIL, 3T3, and SV40/3T3 cells in culture. 2. The fatty acid composition of the resulting phosphonium phosphatidylcholine is similar to that of phosphatidylcholine. 3. The rate of synthesis and degradation of phosphatidylcholine and of the phosphonium analogue are similar. 4. Phospholipid-exchange protein does not distinguish between phosphatidylcholine and the phosphonium analogue. 5. By contrast, incorporation of phosphonium choline into sphingomyelin occurs to only a minor extent. 6. It is concluded that, since the enzymes involved in the turnover of phosphatidylcholine do not discriminate between quaternary N and quaternary P in the polar head-group region, phosphonium choline should prove to be a useful probe for 31P nuclear-magnetic-resonance (n.m.r.) studies of natural membranes."} {"id": "PMID:1275903", "title": "Variants of hamster fibroblasts resistant to Ricinus communis toxin (ricin).", "content": "1. Variant baby-hamster kidney (BHK) cell lines were isolated that grow in the presence of high concentrations of ricin, the toxic lectin of castor beans (Ricinus communis). The variant lines were independently derived from several cultures of normal BHK cells which had been exposed to the mutagen, methyl-N-nitro-N-nitrosoguanidine, before selection by ricin. 2. The cell lines maintain a high degree of resistance to ricin after growth in lectin-free medium for prolonged periods and therefore exhibit stable phenotypes that are different from normal BHK cells. 3. A preliminary classification of the phenotypes was made. Several cell lines bind normal amounts of 125I-labelled ricin, whereas other bind the lectin poorly. 4. A loss of surface receptors for two other lectins, R. communis RCA and Axinella polyploides, which have specificities similar to ricin, was also found in some but not all of the cell lines showing decreased surface concentrations of ricin receptors. 5. The binding to the ricin-resistant cells of lectins of different sugar specificity, namely Lens culinaris lectin and concanavalin A, was similar to, or higher than, to normal BHK cells. 6. Several of the ricin-resistant cell lines were shown to be cross-resistant to the weak cytotoxicity of Phaseolus vulgaris lectin. By contrast, some cell lines were more sensitive to concanavalin A than were normal BHK cells.", "contents": "Variants of hamster fibroblasts resistant to Ricinus communis toxin (ricin). 1. Variant baby-hamster kidney (BHK) cell lines were isolated that grow in the presence of high concentrations of ricin, the toxic lectin of castor beans (Ricinus communis). The variant lines were independently derived from several cultures of normal BHK cells which had been exposed to the mutagen, methyl-N-nitro-N-nitrosoguanidine, before selection by ricin. 2. The cell lines maintain a high degree of resistance to ricin after growth in lectin-free medium for prolonged periods and therefore exhibit stable phenotypes that are different from normal BHK cells. 3. A preliminary classification of the phenotypes was made. Several cell lines bind normal amounts of 125I-labelled ricin, whereas other bind the lectin poorly. 4. A loss of surface receptors for two other lectins, R. communis RCA and Axinella polyploides, which have specificities similar to ricin, was also found in some but not all of the cell lines showing decreased surface concentrations of ricin receptors. 5. The binding to the ricin-resistant cells of lectins of different sugar specificity, namely Lens culinaris lectin and concanavalin A, was similar to, or higher than, to normal BHK cells. 6. Several of the ricin-resistant cell lines were shown to be cross-resistant to the weak cytotoxicity of Phaseolus vulgaris lectin. By contrast, some cell lines were more sensitive to concanavalin A than were normal BHK cells."} {"id": "PMID:1275904", "title": "Arterio-venous differences of choline and choline lipids across the brain of rat and rabbit.", "content": "The concentration of unesterified choline in the plasma in the jugular vein of the rat (0.85 nmol/ml) was found to be three times that of the arterial supply to the brain (0.25 nmol/ml), indicating a higher efflux than uptake of unesterified choline by the brain. No such difference was found for the rabbit and no arterio-venous difference for phosphatidylcholine or lysophosphatidylcholine was observed in either species. No arterio-venous difference was found for choline in blood cells. The infusion of [Me-3H]choline into the circulation of the rat or rabbit indicated an uptake of radioactive choline by the brain and an efflux of non-radioactive choline. In the rabbit such an infusion produced a steady rise in the labelling of phosphatidylcholine and lysophosphatidylcholine in the plasma. When [14C2]ethanolamine was injected intraperitoneally into the rat there was a labelling of phosphatidylcholine, lysophosphatidylcholine and sphingomyelin in the plasma and cells of blood from the jugular vein and the arterial supply, as well as in the brain tissue. However, no labelling of unesterified choline in these tissues could be detected. Unesterified choline was shown to be liberated into the plasma when whole blood from the rat or man, but not the rabbit, was incubated for short periods at 30 degrees C.", "contents": "Arterio-venous differences of choline and choline lipids across the brain of rat and rabbit. The concentration of unesterified choline in the plasma in the jugular vein of the rat (0.85 nmol/ml) was found to be three times that of the arterial supply to the brain (0.25 nmol/ml), indicating a higher efflux than uptake of unesterified choline by the brain. No such difference was found for the rabbit and no arterio-venous difference for phosphatidylcholine or lysophosphatidylcholine was observed in either species. No arterio-venous difference was found for choline in blood cells. The infusion of [Me-3H]choline into the circulation of the rat or rabbit indicated an uptake of radioactive choline by the brain and an efflux of non-radioactive choline. In the rabbit such an infusion produced a steady rise in the labelling of phosphatidylcholine and lysophosphatidylcholine in the plasma. When [14C2]ethanolamine was injected intraperitoneally into the rat there was a labelling of phosphatidylcholine, lysophosphatidylcholine and sphingomyelin in the plasma and cells of blood from the jugular vein and the arterial supply, as well as in the brain tissue. However, no labelling of unesterified choline in these tissues could be detected. Unesterified choline was shown to be liberated into the plasma when whole blood from the rat or man, but not the rabbit, was incubated for short periods at 30 degrees C."} {"id": "PMID:1275905", "title": "Lipid synthesis in vivo by tissues of the maternal and foetal guinea pig.", "content": "The rate of lipid biosynthesis in vivo was determined in pregnant guinea pigs after maternal and foetal injections of 3H2O. Synthesis in the maternal tissues was low and in the foetal liver and adipose tissues relatively high. In the foetal liver it reached a peak at about two-thirds of gestation, whereas that in the foetal adipose tissue occurred later. These results were used to support the view that lipid synthesis in the foetal guinea-pig liver at two-thirds of gestation is largely from short-chain fatty acids, whereas in foetal adipose tissue glucose is probably the major substrate.", "contents": "Lipid synthesis in vivo by tissues of the maternal and foetal guinea pig. The rate of lipid biosynthesis in vivo was determined in pregnant guinea pigs after maternal and foetal injections of 3H2O. Synthesis in the maternal tissues was low and in the foetal liver and adipose tissues relatively high. In the foetal liver it reached a peak at about two-thirds of gestation, whereas that in the foetal adipose tissue occurred later. These results were used to support the view that lipid synthesis in the foetal guinea-pig liver at two-thirds of gestation is largely from short-chain fatty acids, whereas in foetal adipose tissue glucose is probably the major substrate."} {"id": "PMID:1275906", "title": "Inhibition of protein synthesis in reticulocyte lysates by trichodermin.", "content": "1. The effect of trichodermin as an inhibitor of eukaryotic protein synthesis was studied in a reticulocyte cell-free system. 2. Trichodermin at a concentration of 25 mug/ml inhibits total protein synthesis instantaneously and stabilizes polyribosome profiles. Conversely, at a concentration of 0.25 mug/ml the drug inhibits total protein synthesis by only 70-75% and allows 30-35% breakdown of the polyribosomes in the system. These effects were compared with those produced by two other drugs (pactamycin and anisomycin) examined under conditions identical with those used for trichodermin.", "contents": "Inhibition of protein synthesis in reticulocyte lysates by trichodermin. 1. The effect of trichodermin as an inhibitor of eukaryotic protein synthesis was studied in a reticulocyte cell-free system. 2. Trichodermin at a concentration of 25 mug/ml inhibits total protein synthesis instantaneously and stabilizes polyribosome profiles. Conversely, at a concentration of 0.25 mug/ml the drug inhibits total protein synthesis by only 70-75% and allows 30-35% breakdown of the polyribosomes in the system. These effects were compared with those produced by two other drugs (pactamycin and anisomycin) examined under conditions identical with those used for trichodermin."} {"id": "PMID:1275907", "title": "Studies on the catabolism of Ng-methylarginine, Ng, Ng-dimethylarginine and Ng, Ng-dimethylarginine in the rabbit.", "content": "1. The routes of elimination of Ng-methylarginine, Ng, Ng-dimethylarginine and Ng, Ng-dimethylarginine were investigated in the rabbit. 2. Analyses showed low plasma concentrations of these amino acids (around 1 nmol/ml) and ratios similar to those found in tissue proteins. The concentrations of these amino acids in extracts of brain, kidney, liver and spleen were similar except that liver had a lower concentration of Ng-methylarginine and Ng, Ng-dimethylarginine. Cerebrospinal fluid contained traces of each amino acid.", "contents": "Studies on the catabolism of Ng-methylarginine, Ng, Ng-dimethylarginine and Ng, Ng-dimethylarginine in the rabbit. 1. The routes of elimination of Ng-methylarginine, Ng, Ng-dimethylarginine and Ng, Ng-dimethylarginine were investigated in the rabbit. 2. Analyses showed low plasma concentrations of these amino acids (around 1 nmol/ml) and ratios similar to those found in tissue proteins. The concentrations of these amino acids in extracts of brain, kidney, liver and spleen were similar except that liver had a lower concentration of Ng-methylarginine and Ng, Ng-dimethylarginine. Cerebrospinal fluid contained traces of each amino acid."} {"id": "PMID:1275908", "title": "The action of phosphatidylinositol-specific phospholipases C on membranes.", "content": "A phospholipase C prepared from lymphocytes readily hydrolysed pure phosphatidyl-inositol but was relatively ineffective against phosphatidylinositol in erythrocyte \"ghosts\" and rat liver microsomal fraction and also against sonicated lipid extracts from these membranes. In contrast, a phospholipase C prepared from Staphylcoccus aureus readily hydrolysed phosphatidylinositol in sonicated lipid extracts but had only low activity against purified phosphatidylinositol. Unlike the enzyme from lymphocytes, the S. aureus phospholipase C did not require Ca2+ for its activity and was inhibited by cations. The previously reported specificity of this enzyme was confirmed by our observation of hydrolysis of approx. 75% of the phosphatidylinositol in ox, sheep and cat erythrocyte \"ghosts\" together with no detectable effect on the major erythrocyte membrane phospholipids. The phosphatidylinositol of rat liver microsomal fraction was hydrolysed only to a maximum of 15%. Some preliminary experiments showed that approx. 60% of the phosphatidylinositol of ox or sheep erythrocytes could be hydrolysed without causing substantial haemolysis.", "contents": "The action of phosphatidylinositol-specific phospholipases C on membranes. A phospholipase C prepared from lymphocytes readily hydrolysed pure phosphatidyl-inositol but was relatively ineffective against phosphatidylinositol in erythrocyte \"ghosts\" and rat liver microsomal fraction and also against sonicated lipid extracts from these membranes. In contrast, a phospholipase C prepared from Staphylcoccus aureus readily hydrolysed phosphatidylinositol in sonicated lipid extracts but had only low activity against purified phosphatidylinositol. Unlike the enzyme from lymphocytes, the S. aureus phospholipase C did not require Ca2+ for its activity and was inhibited by cations. The previously reported specificity of this enzyme was confirmed by our observation of hydrolysis of approx. 75% of the phosphatidylinositol in ox, sheep and cat erythrocyte \"ghosts\" together with no detectable effect on the major erythrocyte membrane phospholipids. The phosphatidylinositol of rat liver microsomal fraction was hydrolysed only to a maximum of 15%. Some preliminary experiments showed that approx. 60% of the phosphatidylinositol of ox or sheep erythrocytes could be hydrolysed without causing substantial haemolysis."} {"id": "PMID:1275909", "title": "Effect of vitamin A nutritional status on the growth of oestrogen-primed chick oviduct.", "content": "Growth and development of the oestrogen-primed oviduct of immature chicks in terms of weight, length, total protein, total RNA, total DNA and total phospholipids are markedly arrested on deprivation of vitamin A; supplementation with retinyl acetate reversed the effect of the deficiency almost fully, whereas retinoic acid was only partly effective.", "contents": "Effect of vitamin A nutritional status on the growth of oestrogen-primed chick oviduct. Growth and development of the oestrogen-primed oviduct of immature chicks in terms of weight, length, total protein, total RNA, total DNA and total phospholipids are markedly arrested on deprivation of vitamin A; supplementation with retinyl acetate reversed the effect of the deficiency almost fully, whereas retinoic acid was only partly effective."} {"id": "PMID:1275910", "title": "Role of oxygen on growth rate and gene activity in cultured chick-embryo heart cells.", "content": "Environmental oxygen is shown to have a regulatory role in growth rate and the mechanism of gene de-repression in chick-embryo heart cells; it modulates the intracellular concentration of polyamines, and this appears to be closely related to histone acetylation.", "contents": "Role of oxygen on growth rate and gene activity in cultured chick-embryo heart cells. Environmental oxygen is shown to have a regulatory role in growth rate and the mechanism of gene de-repression in chick-embryo heart cells; it modulates the intracellular concentration of polyamines, and this appears to be closely related to histone acetylation."} {"id": "PMID:1275911", "title": "The conversion of 3-Hydroxy-2,4,5-trihydroxymethylpyridine into pyridoxine by Kloeckera apiculata.", "content": "Kloeckera apiculata, a vitamin B-6-dependent yeast, grows in the presence of 3-hydroxy-2,4,5-trihydroxymethylpyridine in vitamin B-6-free media. On a molar basis the growth-promoting activity of this compound is approximately one-tenth that of other forms of vitamin B-6. [G-3H]3-Hydroxy-2,4,5-trihydroxymethylpyridine is converted into radioactive vitamin B-6 compounds of the same specific radioactivity by growing cultures of K. apiculata.", "contents": "The conversion of 3-Hydroxy-2,4,5-trihydroxymethylpyridine into pyridoxine by Kloeckera apiculata. Kloeckera apiculata, a vitamin B-6-dependent yeast, grows in the presence of 3-hydroxy-2,4,5-trihydroxymethylpyridine in vitamin B-6-free media. On a molar basis the growth-promoting activity of this compound is approximately one-tenth that of other forms of vitamin B-6. [G-3H]3-Hydroxy-2,4,5-trihydroxymethylpyridine is converted into radioactive vitamin B-6 compounds of the same specific radioactivity by growing cultures of K. apiculata."} {"id": "PMID:1275912", "title": "Amino acid transport in normal and glutathione-deficient sheep erythrocytes.", "content": "1. Uptake rates for 23 amino acids were measured for both normal (high-GSH) and GSH-deficient (low-GSH) erythrocytes from Finnish Landrace sheep. 2. Compared with high-GSH cells, low-GSH cells had a markedly diminished permeability to D-alanine, L-alanine, alpha-amino-n-butyrate, valine, cysteine, serine, threonine, asparagine, lysine and ornithine. Smaller differences were observed for glycine and proline, whereas uptake of the other amino acids was not significantly different in the two cell types.", "contents": "Amino acid transport in normal and glutathione-deficient sheep erythrocytes. 1. Uptake rates for 23 amino acids were measured for both normal (high-GSH) and GSH-deficient (low-GSH) erythrocytes from Finnish Landrace sheep. 2. Compared with high-GSH cells, low-GSH cells had a markedly diminished permeability to D-alanine, L-alanine, alpha-amino-n-butyrate, valine, cysteine, serine, threonine, asparagine, lysine and ornithine. Smaller differences were observed for glycine and proline, whereas uptake of the other amino acids was not significantly different in the two cell types."} {"id": "PMID:1275913", "title": "Synthesis and turnover of plasma-membrane proteins and glycoproteins in a neuroblastoma cell line.", "content": "A kinetic analysis of the appearance of 14C-labelled proteins in the surface membranes isolated from exponentially growing neuroblastoma cells (N2a) showed that the total membrane proteins reached a steady-state specific radioactivity in 18-20 h. However, examination of individual protein bands resolved by sodium dodecyl sulphate-urea-polyacrylamide-gel electrophoresis illustrated that differences in the kinetics of specific surface-membrane proteins could be detected. Although most of the protein bands reached a steady-state specific radioactivity at a time similar to that for total membrane proteins, at least two bands (mol. wt. 180000 and 130000) attained the steady-state within 8-10 h. It was shown by the use of dual-labelling techniques that these two protein bands turned over in the surface membranes of neuroblastoma N2a cells at least 180 and 150% faster than the total membrane protein. These two proteins were glycosylated and located on the outer surface of the cells, since they were labelled with radioactive carbohydrates and readily removed by treatment of the intact neuroblastoma cell with proteinases.", "contents": "Synthesis and turnover of plasma-membrane proteins and glycoproteins in a neuroblastoma cell line. A kinetic analysis of the appearance of 14C-labelled proteins in the surface membranes isolated from exponentially growing neuroblastoma cells (N2a) showed that the total membrane proteins reached a steady-state specific radioactivity in 18-20 h. However, examination of individual protein bands resolved by sodium dodecyl sulphate-urea-polyacrylamide-gel electrophoresis illustrated that differences in the kinetics of specific surface-membrane proteins could be detected. Although most of the protein bands reached a steady-state specific radioactivity at a time similar to that for total membrane proteins, at least two bands (mol. wt. 180000 and 130000) attained the steady-state within 8-10 h. It was shown by the use of dual-labelling techniques that these two protein bands turned over in the surface membranes of neuroblastoma N2a cells at least 180 and 150% faster than the total membrane protein. These two proteins were glycosylated and located on the outer surface of the cells, since they were labelled with radioactive carbohydrates and readily removed by treatment of the intact neuroblastoma cell with proteinases."} {"id": "PMID:1275914", "title": "Subcellular distribution and activity in different rat tissues of a deoxyinosine-activated nucleotidase.", "content": "A nucleotidase (EC 3.1.3.31) isolated previously from rat liver cytosol was specifically measured in 14 different rat tissues and in subcellular fractions of liver and spleen, taking advantage of the stimulation exerted on it by deoxyinosine. The intracellular distribution studies showed that the enzyme is located almost entirely in the soluble cytoplasm except for the possible presence of 1-2% of the enzyme in the nucleus. The enzyme was present in various amounts in all the tissues studied. Spleen, thymus, and intestinal mucosa showed higher specific activities than any other tissue. On a per cell basis spleen, liver and intestinal mucosa had the highest enzyme activity, whereas bone marrow, brain, thymus, heart and skeletal muscle had activities in the lower range. The results may suggest that the enzyme plays a role in the recovery of endogenous nuclear material for nucleic acid synthesis.", "contents": "Subcellular distribution and activity in different rat tissues of a deoxyinosine-activated nucleotidase. A nucleotidase (EC 3.1.3.31) isolated previously from rat liver cytosol was specifically measured in 14 different rat tissues and in subcellular fractions of liver and spleen, taking advantage of the stimulation exerted on it by deoxyinosine. The intracellular distribution studies showed that the enzyme is located almost entirely in the soluble cytoplasm except for the possible presence of 1-2% of the enzyme in the nucleus. The enzyme was present in various amounts in all the tissues studied. Spleen, thymus, and intestinal mucosa showed higher specific activities than any other tissue. On a per cell basis spleen, liver and intestinal mucosa had the highest enzyme activity, whereas bone marrow, brain, thymus, heart and skeletal muscle had activities in the lower range. The results may suggest that the enzyme plays a role in the recovery of endogenous nuclear material for nucleic acid synthesis."} {"id": "PMID:1275915", "title": "The regulation of haemoglobin synthesis in cultured chick blastoderms by steroids related to 5beta-androstane.", "content": "1. After 24h of incubation, the blastoderm may be dissected from the early developing chick embryo and successfully maintained under conditions of organ culture in vitro. 2. Low concentrations of steroids related to 5beta-androstane stimulate the synthesis of foetal haemoglobins, types E and P, in a highly steroid- and tissue-specific manner.", "contents": "The regulation of haemoglobin synthesis in cultured chick blastoderms by steroids related to 5beta-androstane. 1. After 24h of incubation, the blastoderm may be dissected from the early developing chick embryo and successfully maintained under conditions of organ culture in vitro. 2. Low concentrations of steroids related to 5beta-androstane stimulate the synthesis of foetal haemoglobins, types E and P, in a highly steroid- and tissue-specific manner."} {"id": "PMID:1275916", "title": "Synthesis of hepatic polyamines, ribonucleic acid and S-adenosylmethionine in normal and oestrogen-treated chicks.", "content": "1. The hepatic synthesis and accumulation of polyamines, RNA and S-adenosylmethionine were studied in normal and oestrogen-treated immature male chicks. 2. Ornithine decarboxylase activity in chick liver and in whole chick embryo homogenate was preferentially located in the soluble supernatant fraction. 3. In general the activities of the enzymes involved in the synthesis of polyamines and S-adenosylmethionine decreased with increasing age.", "contents": "Synthesis of hepatic polyamines, ribonucleic acid and S-adenosylmethionine in normal and oestrogen-treated chicks. 1. The hepatic synthesis and accumulation of polyamines, RNA and S-adenosylmethionine were studied in normal and oestrogen-treated immature male chicks. 2. Ornithine decarboxylase activity in chick liver and in whole chick embryo homogenate was preferentially located in the soluble supernatant fraction. 3. In general the activities of the enzymes involved in the synthesis of polyamines and S-adenosylmethionine decreased with increasing age."} {"id": "PMID:1275956", "title": "[Evaluation of the use of sodium bicarbonate in a group of children with diarrhea, 10 per cent dehydration and metabolic acidosis].", "content": "Considering the disparity of criteria regarding the use of sodium bicarbonate in the management of infants with diarrhea, dehydration and metabolic acidosis, a prospective study was done in 25 infants (13 managed without and 12 with bicarbonate) where it was demonstrated; a) The use of bicarbonate does not lead to a more rapid correction of the metabolic acidosis. b) Bicarbonate should not be used in patients with serum bicarbonate levels of 5 mEq/1. or over. c) Patients with dehydration and metabolic acidosis show hyperglycemia that returns to normal when the dehydration is corrected. This fact is of great interest because these children should not be considered nor managed as diabetics.", "contents": "[Evaluation of the use of sodium bicarbonate in a group of children with diarrhea, 10 per cent dehydration and metabolic acidosis]. Considering the disparity of criteria regarding the use of sodium bicarbonate in the management of infants with diarrhea, dehydration and metabolic acidosis, a prospective study was done in 25 infants (13 managed without and 12 with bicarbonate) where it was demonstrated; a) The use of bicarbonate does not lead to a more rapid correction of the metabolic acidosis. b) Bicarbonate should not be used in patients with serum bicarbonate levels of 5 mEq/1. or over. c) Patients with dehydration and metabolic acidosis show hyperglycemia that returns to normal when the dehydration is corrected. This fact is of great interest because these children should not be considered nor managed as diabetics."} {"id": "PMID:1275957", "title": "Gonadal changes in nephrological patients treated with cyclophosphamide.", "content": "Therapeutic use of immunosupressive drugs in progressive renal diseases has increased during the last decade. Information concerned severe gonadal damage after such therapy, stresses the need for careful evaluation in each particular case before deciding to use these drugs. Gonadal lesions were investigated in 18 patients who were treated with cyclophosphamide and in one who received chlorambucil at variable doses and length of time; there were frequent relapses in patients with idiopathic nephrotic syndrome and with progressive forms of glomerulonephritis. Nine patients were females and received cyclophosphamide therapy at the ages of 11 a 16 years, being evaluated from 11 to 22 years of age with vaginal smears, gonadotropins and 17-ketosteroids. No alterations were found in these parameters and two of the girls became pregnant and had successful deliveries of healthy babies. Ten patients were males; one of them received chlorambucil and all the others received cyclophosphamide at the ages of 8 to 15 years; they were evaluated from 9 to 19 years of age. Because of their ages, gonadal function was not studied in 3 children, but the other 7 showed azoospermia, testicular atrophy was present in four out of these patients in whom testicular biopsy was performed. The patient who received chlorambucil was among this group. From these results and from the literature, we conclude: 1) immunosuppressive therapy is less risky in girls than in boys; 2) it is imperative to evaluate the risk/benefit ratio before deciding this therapy in any case and 3) doses not above 2 mg/kg/day and for periods no longer than 6 weeks may be considered safe.", "contents": "Gonadal changes in nephrological patients treated with cyclophosphamide. Therapeutic use of immunosupressive drugs in progressive renal diseases has increased during the last decade. Information concerned severe gonadal damage after such therapy, stresses the need for careful evaluation in each particular case before deciding to use these drugs. Gonadal lesions were investigated in 18 patients who were treated with cyclophosphamide and in one who received chlorambucil at variable doses and length of time; there were frequent relapses in patients with idiopathic nephrotic syndrome and with progressive forms of glomerulonephritis. Nine patients were females and received cyclophosphamide therapy at the ages of 11 a 16 years, being evaluated from 11 to 22 years of age with vaginal smears, gonadotropins and 17-ketosteroids. No alterations were found in these parameters and two of the girls became pregnant and had successful deliveries of healthy babies. Ten patients were males; one of them received chlorambucil and all the others received cyclophosphamide at the ages of 8 to 15 years; they were evaluated from 9 to 19 years of age. Because of their ages, gonadal function was not studied in 3 children, but the other 7 showed azoospermia, testicular atrophy was present in four out of these patients in whom testicular biopsy was performed. The patient who received chlorambucil was among this group. From these results and from the literature, we conclude: 1) immunosuppressive therapy is less risky in girls than in boys; 2) it is imperative to evaluate the risk/benefit ratio before deciding this therapy in any case and 3) doses not above 2 mg/kg/day and for periods no longer than 6 weeks may be considered safe."} {"id": "PMID:1275958", "title": "[Megaloblastic anemia in the recovery of the malnourished child].", "content": "With the purpose of analyzing the evolution in weight before and after treatment of megaloblastic anemia with folic acid, we studied the clinical changes and the evolution in weight in 8 malnourished children who developed this type of anemia during their recovery. Seven out of the 8 cases were less than 20 months of age; 5 of them came from mothers who had had five or more pregnancies; in 7 a history of diarrhea of prolonged course was presented and 2 cases had been given sodium diphenylhydantoin. Increase in weight before treatment of anemia with folic acid was lesser than the one for the days following treatment in seven of the patients. Simultaneously, an important change in behavior was appreciated, without being possible to atribute this change or the increase in weight to a quantitative change favorable to the ingestion of proteins and calories.", "contents": "[Megaloblastic anemia in the recovery of the malnourished child]. With the purpose of analyzing the evolution in weight before and after treatment of megaloblastic anemia with folic acid, we studied the clinical changes and the evolution in weight in 8 malnourished children who developed this type of anemia during their recovery. Seven out of the 8 cases were less than 20 months of age; 5 of them came from mothers who had had five or more pregnancies; in 7 a history of diarrhea of prolonged course was presented and 2 cases had been given sodium diphenylhydantoin. Increase in weight before treatment of anemia with folic acid was lesser than the one for the days following treatment in seven of the patients. Simultaneously, an important change in behavior was appreciated, without being possible to atribute this change or the increase in weight to a quantitative change favorable to the ingestion of proteins and calories."} {"id": "PMID:1275959", "title": "[Iron and transferrin metabolism].", "content": "The study comprised 36 patients who were divided into two groups. In the first one, there were acute or chronic infectious diseases and the second was a control group. In all of them, the following laboratory counts were done: hemoglobin, hematocrit, leukocyte; also, measurement of protein electrophoresis, of serum iron and of total fixation capacity of iron (transferrin). The procedure was that of a blind study, so that the laboratories responsible for the measurements were not given any clinical information on the different patients. Hypochromic anemia of different degrees of severeness was reported in all infected patients and was attributted to nutritional and infectious factors. In spite of decreased levels of hemoglobin and iron, it was shown that transferrin did not rise, but otherwise, dropped in these patients; therefore, the capacity to convey and fix iron is decreased. This would be a fact resulting in a greater susceptibility, to suffer infections, as has been confirmed in previous studies. A close relationship was found at pediatric level among hypochromic anemia, drop in transferrin levels, poor nutrition and increase of infectious diseases.", "contents": "[Iron and transferrin metabolism]. The study comprised 36 patients who were divided into two groups. In the first one, there were acute or chronic infectious diseases and the second was a control group. In all of them, the following laboratory counts were done: hemoglobin, hematocrit, leukocyte; also, measurement of protein electrophoresis, of serum iron and of total fixation capacity of iron (transferrin). The procedure was that of a blind study, so that the laboratories responsible for the measurements were not given any clinical information on the different patients. Hypochromic anemia of different degrees of severeness was reported in all infected patients and was attributted to nutritional and infectious factors. In spite of decreased levels of hemoglobin and iron, it was shown that transferrin did not rise, but otherwise, dropped in these patients; therefore, the capacity to convey and fix iron is decreased. This would be a fact resulting in a greater susceptibility, to suffer infections, as has been confirmed in previous studies. A close relationship was found at pediatric level among hypochromic anemia, drop in transferrin levels, poor nutrition and increase of infectious diseases."} {"id": "PMID:1275960", "title": "[Liver hydatidosis in an eight-year-old child].", "content": "The first pediatric case of hepatic hydatidosis diagnosed in Mexico is reported. Previous to surgery, the diagnosis was established, based on a cystic tumor of the liver, the X ray findings, defects in the liver uptake, eosinophilia and Casoni's positive intradermal reaction. Besides, the immunoelectrophoresis test showed specific antibodies. Clinical and epidemiological considerations, related with the pathology and treatment of hydatidic disease are made, stressing the importance to know the symtoms of the illness, in order to establish the diagnosis and treatment. Likewise, the prognosis is evaluated considering the remaining cysts of the liver and the possible seeding of the parasite into the peritoneal cavity. Pertinent literature on the subject is reviewed.", "contents": "[Liver hydatidosis in an eight-year-old child]. The first pediatric case of hepatic hydatidosis diagnosed in Mexico is reported. Previous to surgery, the diagnosis was established, based on a cystic tumor of the liver, the X ray findings, defects in the liver uptake, eosinophilia and Casoni's positive intradermal reaction. Besides, the immunoelectrophoresis test showed specific antibodies. Clinical and epidemiological considerations, related with the pathology and treatment of hydatidic disease are made, stressing the importance to know the symtoms of the illness, in order to establish the diagnosis and treatment. Likewise, the prognosis is evaluated considering the remaining cysts of the liver and the possible seeding of the parasite into the peritoneal cavity. Pertinent literature on the subject is reviewed."} {"id": "PMID:1275961", "title": "[Medullary carcinoma of the thyroid gland. Report of a case].", "content": "The case of a twelve years old boy with unilateral medullary carcinoma of the thyroid gland, whose main symptoms were cough, hemoptisis, fever and weight loss is reported. The diagnosis was made by lymph node biopsy, high levels of serum calcitonin and a positive skin test for histaminase. The main clinical, anatomical and genetic features of this tumor are discussed. The familial study did not show any other affected member. Therefore, it was considered as a sporadic case. Emphasis is made on the diagnostic methodolgy.", "contents": "[Medullary carcinoma of the thyroid gland. Report of a case]. The case of a twelve years old boy with unilateral medullary carcinoma of the thyroid gland, whose main symptoms were cough, hemoptisis, fever and weight loss is reported. The diagnosis was made by lymph node biopsy, high levels of serum calcitonin and a positive skin test for histaminase. The main clinical, anatomical and genetic features of this tumor are discussed. The familial study did not show any other affected member. Therefore, it was considered as a sporadic case. Emphasis is made on the diagnostic methodolgy."} {"id": "PMID:1275963", "title": "[Electrocardiography and central venous pressure during exchange transfusion].", "content": "Electrocardiographic and central venous pressure (CVP) records were taken during 30 exchange transfusions practiced to 26 newborns. The technique of two vessels was employed in 26 cases. Operations lasted 84.8 minutes as an average. There was only one death and the transfusion was discontinued in another case because of clinical aggravation and many disorders in the ECG. These disorders reached 40% of the cases with marked predominance of hypocalcemia which appeared as \"initial\" in three babies with previous history of transfusion. CVP was usually higher than reported for normal newborns and was equal to values found in a similar group of isoimmuned infants. It was high in seven cases, out of which, four complained of severe hemolytic disease and obviously, of anemia. Initial removal of 10 to 20 ml. of blood in these cases, allowed a drop of 3 to 4 cm. of H2O in CVP and its further maintenance at stable levels.", "contents": "[Electrocardiography and central venous pressure during exchange transfusion]. Electrocardiographic and central venous pressure (CVP) records were taken during 30 exchange transfusions practiced to 26 newborns. The technique of two vessels was employed in 26 cases. Operations lasted 84.8 minutes as an average. There was only one death and the transfusion was discontinued in another case because of clinical aggravation and many disorders in the ECG. These disorders reached 40% of the cases with marked predominance of hypocalcemia which appeared as \"initial\" in three babies with previous history of transfusion. CVP was usually higher than reported for normal newborns and was equal to values found in a similar group of isoimmuned infants. It was high in seven cases, out of which, four complained of severe hemolytic disease and obviously, of anemia. Initial removal of 10 to 20 ml. of blood in these cases, allowed a drop of 3 to 4 cm. of H2O in CVP and its further maintenance at stable levels."} {"id": "PMID:1275965", "title": "[Development and prognosis of diffuse endocapillary and focal extracapillary proliferative glomerulonephritis].", "content": "Early renal biopsies performed in children with primary nephritic syndrome of acute onset have identified various glomerular pathological patterns with distinct evolution. Complete recovery has been observed in those cases with diffuse endocapillary proliferation. However, progressive disease has resulted from most of the other forms. A histological type characterized by diffuse glomerular endocapillary proliferation with a variable number of glomeruli affected by extracapillary proliferation with crescents, has been observed. A diffuse form of this entity, that is, crescents in 80 to 100 per cent of the glomeruli, has been described in the so-called \"rapidly progressive glomerulonephritis\". This lesion usually progresses to renal insufficiency in less than six months. Information concerning the focal form, that is, the presence of crescents in less than 80 per cent of the glomeruli, is limited and the long-term prognosis of this morphological finding has not been conclusively established. This communication deals with: 1) history and initial clinical features in 48 patients with focal endo and extracapillary glomerulonephritis, and 2) the correlations between streptococcal etiology, initial features, percentage of glomeruli with crescents and the final outcome, in 27 cases followed for more than two years. Age of patients at the onset of the disease was between 11 months and 14 years; 63 percent of the patients were male. Streptococcal infection was documented in 20 out of the 48 cases. Nephritic syndrome at onset was found in all the 48 cases. Twenty-nine patients had significant proteinuria and in 16 of these, the characteristics of the nephrotic syndrome were also present; 10 patients presented severe arterial hypertension and in other 6, acute renal failure was an initial feature.", "contents": "[Development and prognosis of diffuse endocapillary and focal extracapillary proliferative glomerulonephritis]. Early renal biopsies performed in children with primary nephritic syndrome of acute onset have identified various glomerular pathological patterns with distinct evolution. Complete recovery has been observed in those cases with diffuse endocapillary proliferation. However, progressive disease has resulted from most of the other forms. A histological type characterized by diffuse glomerular endocapillary proliferation with a variable number of glomeruli affected by extracapillary proliferation with crescents, has been observed. A diffuse form of this entity, that is, crescents in 80 to 100 per cent of the glomeruli, has been described in the so-called \"rapidly progressive glomerulonephritis\". This lesion usually progresses to renal insufficiency in less than six months. Information concerning the focal form, that is, the presence of crescents in less than 80 per cent of the glomeruli, is limited and the long-term prognosis of this morphological finding has not been conclusively established. This communication deals with: 1) history and initial clinical features in 48 patients with focal endo and extracapillary glomerulonephritis, and 2) the correlations between streptococcal etiology, initial features, percentage of glomeruli with crescents and the final outcome, in 27 cases followed for more than two years. Age of patients at the onset of the disease was between 11 months and 14 years; 63 percent of the patients were male. Streptococcal infection was documented in 20 out of the 48 cases. Nephritic syndrome at onset was found in all the 48 cases. Twenty-nine patients had significant proteinuria and in 16 of these, the characteristics of the nephrotic syndrome were also present; 10 patients presented severe arterial hypertension and in other 6, acute renal failure was an initial feature."} {"id": "PMID:1275966", "title": "[Recurrent hematuria of glomerular origin].", "content": "Nine hundred and forty children with hematuria were admitted to the nephrology service from 1958 to 1973. Percutaneous renal biopsies were performed in all of them. Thirty cases out of this group had recurrent hematuria and constitute the clinical material of this study. The clinical picture was: acute nephrotic syndrome in 19; monosymptomatic hematuria in 8, anaphylactoid purpura nephritis in 2, and hematuria associated with nephrotic syndrome in one patient. All patients with nephritic syndrome showed in their biopsies various types of glomerular lesions; most of the patients with monosymptomatic hematuria had normal glomeruli; at the light microscopy, the immunofluorescence was positive in some of them. Both patients with anaphylactoid nephritis showed diffuse endocapillary and focal extracapillary proliferation and in the only one with nephrotic syndrome, the hematuria was familial and the biopsy showed features of Alport's syndrome. Twenty-four patients who were followed for over two years showed no relationship between the age of onset, sex, initial significant proteinuria, hypertension, frequency of bouts of hematuria and the clinical evolution. At the end of the study, 7 patients had prolonged remission: the light microscopy showed normal glomeruli, endocapillary proliferation and endo and extracapillary proliferation with less than 30% of the glomeruli affected by \"crescents\". The remaining cases were still active and one of them with endo and extracapillary glomerulonephritis with more than 30% of the glomeruli affected by \"crescents\", developed chronic renal insufficiency. In conclusion, the prognosis of recurrent hematuria of glomerular origen is related with the type of glomerular lesions and constitutes an indication for renal biopsy. Renal specimens must be studied under light microscopy and immunofluorescence techniques; electromicroscopy is required when hematuria is present in more than one member of the family.", "contents": "[Recurrent hematuria of glomerular origin]. Nine hundred and forty children with hematuria were admitted to the nephrology service from 1958 to 1973. Percutaneous renal biopsies were performed in all of them. Thirty cases out of this group had recurrent hematuria and constitute the clinical material of this study. The clinical picture was: acute nephrotic syndrome in 19; monosymptomatic hematuria in 8, anaphylactoid purpura nephritis in 2, and hematuria associated with nephrotic syndrome in one patient. All patients with nephritic syndrome showed in their biopsies various types of glomerular lesions; most of the patients with monosymptomatic hematuria had normal glomeruli; at the light microscopy, the immunofluorescence was positive in some of them. Both patients with anaphylactoid nephritis showed diffuse endocapillary and focal extracapillary proliferation and in the only one with nephrotic syndrome, the hematuria was familial and the biopsy showed features of Alport's syndrome. Twenty-four patients who were followed for over two years showed no relationship between the age of onset, sex, initial significant proteinuria, hypertension, frequency of bouts of hematuria and the clinical evolution. At the end of the study, 7 patients had prolonged remission: the light microscopy showed normal glomeruli, endocapillary proliferation and endo and extracapillary proliferation with less than 30% of the glomeruli affected by \"crescents\". The remaining cases were still active and one of them with endo and extracapillary glomerulonephritis with more than 30% of the glomeruli affected by \"crescents\", developed chronic renal insufficiency. In conclusion, the prognosis of recurrent hematuria of glomerular origen is related with the type of glomerular lesions and constitutes an indication for renal biopsy. Renal specimens must be studied under light microscopy and immunofluorescence techniques; electromicroscopy is required when hematuria is present in more than one member of the family."} {"id": "PMID:1275964", "title": "[D-xylose absorption and weight increase during treatment of celiac disease].", "content": "Four patients were studied during the early phase of celiac disease treatment, observing a close correlation between weight increase and the ability to absorb d-xylose.", "contents": "[D-xylose absorption and weight increase during treatment of celiac disease]. Four patients were studied during the early phase of celiac disease treatment, observing a close correlation between weight increase and the ability to absorb d-xylose."} {"id": "PMID:1275967", "title": "[Evaluation of the urinary and plasma urea ratio and osmolarity in newborn infants and malnourished children with pathological and normal renal function].", "content": "Previous evaluation of diagnostic tests for acute renal failure in children demonstrated that osmolality urine/plasms (U/P) ratio below 1.3, urea ratio below 4.8 and a negative mannitol test (absence of a diurteic response within one hour after intravenous administration of 60 ml/m2 of 12.5% mannitol solution) may be considered as valuable factors in this diagnosis. However, the validity of those ratios were in doubt in selected populations such as newborns and in severe malnourished children in whom an impairment in concentrating urine capacity can be anticipated. With the purpose to test the validity of these parameters, a group of 53 newborns and 68 children with severe malnutrition were studied. They were admitted to the hospital with dehydration secondary to acute diarrhea presenting oliguria and hyperpnea and before any treatment was given, urine and blood samples were taken to determine urea and osmolality U/P ratios besides routine chemistries. Mannitol test was performed when urine could not be obtained and in some cases in whom U/P results deserved confirmation with the biological test. Seven of the 53 newborn patients developed acute renal failure with negative mannitol test and further clinical course of persistent oliguria. Urea and osmolality U/P ratios were 3.0 +/- 1.5 and 1.07 +/- 0.01 respectively, whereas the remaining 46 newborns had afterwards an uneventful recovery presenting U/P ratios of 12.4 +/- 8.5 for urea and 1.32 +/- 0.57 for osmolality. The difference between the average values of urea U/P ratio of the patients with acute renal failure and those with functional oliguria, were statistically significant at the level of p less than 0.01, but there was no significant difference between osmolality ratio values.", "contents": "[Evaluation of the urinary and plasma urea ratio and osmolarity in newborn infants and malnourished children with pathological and normal renal function]. Previous evaluation of diagnostic tests for acute renal failure in children demonstrated that osmolality urine/plasms (U/P) ratio below 1.3, urea ratio below 4.8 and a negative mannitol test (absence of a diurteic response within one hour after intravenous administration of 60 ml/m2 of 12.5% mannitol solution) may be considered as valuable factors in this diagnosis. However, the validity of those ratios were in doubt in selected populations such as newborns and in severe malnourished children in whom an impairment in concentrating urine capacity can be anticipated. With the purpose to test the validity of these parameters, a group of 53 newborns and 68 children with severe malnutrition were studied. They were admitted to the hospital with dehydration secondary to acute diarrhea presenting oliguria and hyperpnea and before any treatment was given, urine and blood samples were taken to determine urea and osmolality U/P ratios besides routine chemistries. Mannitol test was performed when urine could not be obtained and in some cases in whom U/P results deserved confirmation with the biological test. Seven of the 53 newborn patients developed acute renal failure with negative mannitol test and further clinical course of persistent oliguria. Urea and osmolality U/P ratios were 3.0 +/- 1.5 and 1.07 +/- 0.01 respectively, whereas the remaining 46 newborns had afterwards an uneventful recovery presenting U/P ratios of 12.4 +/- 8.5 for urea and 1.32 +/- 0.57 for osmolality. The difference between the average values of urea U/P ratio of the patients with acute renal failure and those with functional oliguria, were statistically significant at the level of p less than 0.01, but there was no significant difference between osmolality ratio values."} {"id": "PMID:1275968", "title": "[S-beta thalassemia hemoglobinopathy. Report of 2 cases in a Mexican family].", "content": "Two new cases of hemoglobin S-beta thalassemia are being reported. Twenty-six relatives are studied. The two cases were classified as Mediterranean variety. The diagnostic problem and the therapeutical possibilities are considered.", "contents": "[S-beta thalassemia hemoglobinopathy. Report of 2 cases in a Mexican family]. Two new cases of hemoglobin S-beta thalassemia are being reported. Twenty-six relatives are studied. The two cases were classified as Mediterranean variety. The diagnostic problem and the therapeutical possibilities are considered."} {"id": "PMID:1275969", "title": "[The pediatrician and the intersexuality problems. I. Classification].", "content": "The author discusses the classification of human intersexuality and considers chromosomic sex, genetic sex, type of sex apparent in the newborn, legal sex, social sex and psychological sex.", "contents": "[The pediatrician and the intersexuality problems. I. Classification]. The author discusses the classification of human intersexuality and considers chromosomic sex, genetic sex, type of sex apparent in the newborn, legal sex, social sex and psychological sex."} {"id": "PMID:1275971", "title": "[Effect of furosemide on water and sodium excretion in apparently normal infants].", "content": "Nine infants without evidence of nephropathy were studied. After a control period, furosemide, 1.0 mg/kg. of body weight, was administered intravenously and urine was collected. In all patients, urinary volume increased from a mean of 0.15 ml/min. during the control period, to 0.69 ml/min. after furosemide and urinary sodium excretion rose from 1.77 micro Eq/min. in the first period, to 50.13 micro Eq/min. in the second. There was no significant change in urinary osmolarity and in serum electrolytes. Three hours after furosemide, all children showed dehydration from light to moderate and saline infusion was necessary. No correlation was found between age and weight of the infants with the response to furosemide. Because this diuretic has an energetic action in infants as in children and adults, it must be used carefully and it is proposed that the initial dose of furosemide in infants be 0.5 mg/kg.", "contents": "[Effect of furosemide on water and sodium excretion in apparently normal infants]. Nine infants without evidence of nephropathy were studied. After a control period, furosemide, 1.0 mg/kg. of body weight, was administered intravenously and urine was collected. In all patients, urinary volume increased from a mean of 0.15 ml/min. during the control period, to 0.69 ml/min. after furosemide and urinary sodium excretion rose from 1.77 micro Eq/min. in the first period, to 50.13 micro Eq/min. in the second. There was no significant change in urinary osmolarity and in serum electrolytes. Three hours after furosemide, all children showed dehydration from light to moderate and saline infusion was necessary. No correlation was found between age and weight of the infants with the response to furosemide. Because this diuretic has an energetic action in infants as in children and adults, it must be used carefully and it is proposed that the initial dose of furosemide in infants be 0.5 mg/kg."} {"id": "PMID:1275973", "title": "[The pediatrician and social sciences].", "content": "The social aspects of child health have been emphasized recently. A better understanding requires of Humanities, Behavioral and Social Sciences, Public Health and Health Sciences. The application of these is requested in the pediatric activities.", "contents": "[The pediatrician and social sciences]. The social aspects of child health have been emphasized recently. A better understanding requires of Humanities, Behavioral and Social Sciences, Public Health and Health Sciences. The application of these is requested in the pediatric activities."} {"id": "PMID:1275974", "title": "[SI units in medicine].", "content": "The current concepts of a standarized reporting system in medicine and in clinical pathology (Systeme International d'Unites. SI); is reviewed. SI units in medicine permit a better physiological approach to the understanding of biochemical alterations of disease. The usefulness of the SI system in different areas of clinical pathology, and a report form of the laboratory are outlined.", "contents": "[SI units in medicine]. The current concepts of a standarized reporting system in medicine and in clinical pathology (Systeme International d'Unites. SI); is reviewed. SI units in medicine permit a better physiological approach to the understanding of biochemical alterations of disease. The usefulness of the SI system in different areas of clinical pathology, and a report form of the laboratory are outlined."} {"id": "PMID:1275984", "title": "Clinical, haemodynamic, and angiographic findings in L\u00f6ffler's eosinophilic endocarditis.", "content": "Detailed haemodynamic and angiographic findings in L\u00f6ffler's endocarditis are presented for the first time in a report of 3 cases of this rare disease. In 2 of the cases the right ventricular cavity was obliterated; in one of them this was shown by biopsy to be caused by organized thrombus. In the third case, there was progressive mitral regurgitation.", "contents": "Clinical, haemodynamic, and angiographic findings in L\u00f6ffler's eosinophilic endocarditis. Detailed haemodynamic and angiographic findings in L\u00f6ffler's endocarditis are presented for the first time in a report of 3 cases of this rare disease. In 2 of the cases the right ventricular cavity was obliterated; in one of them this was shown by biopsy to be caused by organized thrombus. In the third case, there was progressive mitral regurgitation."} {"id": "PMID:1275985", "title": "Vectorcardiographic study of aberrant conduction anterior displacement of QRS: another form of intraventricular block.", "content": "Aberrant ventricular conduction was induced in 44 subjects by introduction of atrial premature beats through a transvenous catheter-electrode. Multiple patterns of aberrant ventricular conduction were obtained in 32 patients and, in the whole group, 116 different configurations were recorded. Of these, 104 showed a classical pattern of mono- or biventricular conduction disturbance. The pattern frequencies were as follows: right bundle-branch block, 28; left anterior hemiblock combined with right bundle-branch block, 21; left anterior hemiblock, 17; left posterior hemiblock combined with right bundle-branch block, 12; left posterior hemiblock, 10; complete left bundle-branch block, 10; and incomplete left bundle-branch block, 6. The remaining 12 configurations could not be classified into the usual categories of intraventricular blocks. In 7 of them, the alterations only consisted of trivial modifications of the QRS contour. In the other 5 instances, aberrant conduction manifested itself by a conspicuous anterior displacement of the QRS loop, with increased duration of anterior forces. The latter observation is worthy of notice, as it indicates that, in the differential diagnosis of the vectorcardiographic pattern characterized by prominent anterior forces, conduction disturbances should be considered a possible aetiological factor in addition to right ventricular hypertrophy, and true posterior wall myocardial infarction.", "contents": "Vectorcardiographic study of aberrant conduction anterior displacement of QRS: another form of intraventricular block. Aberrant ventricular conduction was induced in 44 subjects by introduction of atrial premature beats through a transvenous catheter-electrode. Multiple patterns of aberrant ventricular conduction were obtained in 32 patients and, in the whole group, 116 different configurations were recorded. Of these, 104 showed a classical pattern of mono- or biventricular conduction disturbance. The pattern frequencies were as follows: right bundle-branch block, 28; left anterior hemiblock combined with right bundle-branch block, 21; left anterior hemiblock, 17; left posterior hemiblock combined with right bundle-branch block, 12; left posterior hemiblock, 10; complete left bundle-branch block, 10; and incomplete left bundle-branch block, 6. The remaining 12 configurations could not be classified into the usual categories of intraventricular blocks. In 7 of them, the alterations only consisted of trivial modifications of the QRS contour. In the other 5 instances, aberrant conduction manifested itself by a conspicuous anterior displacement of the QRS loop, with increased duration of anterior forces. The latter observation is worthy of notice, as it indicates that, in the differential diagnosis of the vectorcardiographic pattern characterized by prominent anterior forces, conduction disturbances should be considered a possible aetiological factor in addition to right ventricular hypertrophy, and true posterior wall myocardial infarction."} {"id": "PMID:1275986", "title": "Morphogenesis of univentricular hearts.", "content": "Two main theories exist for the explanation of univentricular hearts. One states that the bulboventricular septum becomes realigned to form the interventricular septum, and that univentricular hearts are a consequence of failure of this realignment. The other states that bulboventricular and interventricular septa are different structures, and that the univentricular heart results from failure of formation of the posterior interventricular septum. Four hearts are described in which both the posterior septum and an anterior bulboventricular septum are present. In each heart, therefore, the right ventricular sinus is separated both from the left ventricular sinus and from a discrete outlet chamber which supports the pulmonary artery. It is argued that these findings militate strongly against theories proposing reorientation of the bulboventricular septum to form the definitive interventricular septum. They support strongly the concept that the definitive right ventricle is formed in part from the bulbus and in part from the primitive ventricle. On the basis of these findings, it is suggested that the distinctive feature of the univentricular heart is absence of the posterior septum. Such hearts can properly be termed 'primitive ventricle'. It is also suggested that hearts with atretic or straddling valves should be included within this category.", "contents": "Morphogenesis of univentricular hearts. Two main theories exist for the explanation of univentricular hearts. One states that the bulboventricular septum becomes realigned to form the interventricular septum, and that univentricular hearts are a consequence of failure of this realignment. The other states that bulboventricular and interventricular septa are different structures, and that the univentricular heart results from failure of formation of the posterior interventricular septum. Four hearts are described in which both the posterior septum and an anterior bulboventricular septum are present. In each heart, therefore, the right ventricular sinus is separated both from the left ventricular sinus and from a discrete outlet chamber which supports the pulmonary artery. It is argued that these findings militate strongly against theories proposing reorientation of the bulboventricular septum to form the definitive interventricular septum. They support strongly the concept that the definitive right ventricle is formed in part from the bulbus and in part from the primitive ventricle. On the basis of these findings, it is suggested that the distinctive feature of the univentricular heart is absence of the posterior septum. Such hearts can properly be termed 'primitive ventricle'. It is also suggested that hearts with atretic or straddling valves should be included within this category."} {"id": "PMID:1275987", "title": "Regional pulmonary blood flow in mitral disease studied by xenon radiospirometry.", "content": "Regional lung perfusion was measured in the sitting position by 4 external detectors after intravenous injection of 133Xe in 24 patients with mitral valve disease and in 8 people with no cardiopulmonary disease acting as normal controls. Right- and left-sided heart catheterization was carried out on the patients on the following day. Mitral valve stenosis was found in 9, mitral valve regurgitation in 8, and both stenosis and regurgitation in the remaining 7. Regional lung perfusion in the normal people fell linearly from the basal to the apical sections of the lungs. The perfusion distribution in patients with mitral valve disease and a pulmonary capillary vein (PCV) pressure lower than 15 mmHg (2-0 kPa) did not differ significantly from that of the controls. A redistribution of the regional perfusion, with an increase in the apical perfusion and a fall in the basal perfusion of the lungs, was seen in patients with a raised PCV pressure. The hyperperfusion of the apical lung sections correlated with the mean pressure in the pulmonary artery (r=+0-795, P less than 0-001), while the basal hypoperfusion correlated with the PCV pressure (r=0-842, P less than 0-001). The PCV pressure can be predicted with an exactitude of +/- 7 mmHg (0-9 kPa) (95% confidence limits). Neither the cardiac index nor the pulmonary vascular resistance correlated with the changes in perfusion. Xenon radiospirometry is a rapid and reliable method for evaluating PCV pressure before or after operation in patients with mitral valve disease.", "contents": "Regional pulmonary blood flow in mitral disease studied by xenon radiospirometry. Regional lung perfusion was measured in the sitting position by 4 external detectors after intravenous injection of 133Xe in 24 patients with mitral valve disease and in 8 people with no cardiopulmonary disease acting as normal controls. Right- and left-sided heart catheterization was carried out on the patients on the following day. Mitral valve stenosis was found in 9, mitral valve regurgitation in 8, and both stenosis and regurgitation in the remaining 7. Regional lung perfusion in the normal people fell linearly from the basal to the apical sections of the lungs. The perfusion distribution in patients with mitral valve disease and a pulmonary capillary vein (PCV) pressure lower than 15 mmHg (2-0 kPa) did not differ significantly from that of the controls. A redistribution of the regional perfusion, with an increase in the apical perfusion and a fall in the basal perfusion of the lungs, was seen in patients with a raised PCV pressure. The hyperperfusion of the apical lung sections correlated with the mean pressure in the pulmonary artery (r=+0-795, P less than 0-001), while the basal hypoperfusion correlated with the PCV pressure (r=0-842, P less than 0-001). The PCV pressure can be predicted with an exactitude of +/- 7 mmHg (0-9 kPa) (95% confidence limits). Neither the cardiac index nor the pulmonary vascular resistance correlated with the changes in perfusion. Xenon radiospirometry is a rapid and reliable method for evaluating PCV pressure before or after operation in patients with mitral valve disease."} {"id": "PMID:1275988", "title": "Immunological studies in congestive cardiomyopathy in Cameroon.", "content": "Significantly higher levels of immunoconglutinin were found in the sera of 40 Cameroonian patients aged between 15 and 80 years with congestive cardiomyopathy than in a matched group of normal Cameroonian controls. C3 values were also abnormal in the group with congestive cardiomyopathy, and a negative correlation was found between the C3 and immunoconglutinin values, indicating complement incorporation into immune complexes. Further, the levels of immunoglobulins G, M, and A were all raised, the most striking increase being of IgM, which was greater than in the normal controls and in a group with 'other cardiac disease' studied for comparison. Complement-fixing autoantibodies to cardiac muscle of the class IgG and IgM were found by immunofluorescence techniques in a significant proportion of the patients with congestive cardiomyopathy. Finally, evidence of trypanosomiasis was found by immunofluorescence tests in 27-5 per cent of patients with congestive cardiomyopathy, compared with 8-5 per cent of patients with other cardiac disease, and 1-9 per cent of normal Cameroonian controls selected randomly. We think that some cases of congestive cardiomyopathy in Cameroon may be caused by untreated subclinical attacks of African trypanosomiasis which produce immune complexes that damage the cardiac tissue where the parasite is lodged. Secondary autoimmune carditis modifies the course of the disease, with the resulting end-stage picture.", "contents": "Immunological studies in congestive cardiomyopathy in Cameroon. Significantly higher levels of immunoconglutinin were found in the sera of 40 Cameroonian patients aged between 15 and 80 years with congestive cardiomyopathy than in a matched group of normal Cameroonian controls. C3 values were also abnormal in the group with congestive cardiomyopathy, and a negative correlation was found between the C3 and immunoconglutinin values, indicating complement incorporation into immune complexes. Further, the levels of immunoglobulins G, M, and A were all raised, the most striking increase being of IgM, which was greater than in the normal controls and in a group with 'other cardiac disease' studied for comparison. Complement-fixing autoantibodies to cardiac muscle of the class IgG and IgM were found by immunofluorescence techniques in a significant proportion of the patients with congestive cardiomyopathy. Finally, evidence of trypanosomiasis was found by immunofluorescence tests in 27-5 per cent of patients with congestive cardiomyopathy, compared with 8-5 per cent of patients with other cardiac disease, and 1-9 per cent of normal Cameroonian controls selected randomly. We think that some cases of congestive cardiomyopathy in Cameroon may be caused by untreated subclinical attacks of African trypanosomiasis which produce immune complexes that damage the cardiac tissue where the parasite is lodged. Secondary autoimmune carditis modifies the course of the disease, with the resulting end-stage picture."} {"id": "PMID:1275989", "title": "A comparison of cardiovascular effects of dobutamine and isoprenaline after open heart surgery.", "content": "In a cross-over study, the cardiovascular effects of dobutamine were assessed in 11 patients who had undergone operation for replacement of the mitral or aortic valve approximately four hours earlier. In 9 of these the effects of isoprenaline were assessed for comparison. Dose-response curves were obtained using four dose levels of dobutamine in the range 1.25-10 mug/kg per min and of isoprenaline in the range of 0.005-0.04 mug/kg per min. Both drugs produced similar dose-dependent increases in heart rate and cardiac output and a dose-dependent decrease in peripheral resistance. Mean arterial pressure was only slightly increased by either drug. The positive inotropic effect of dobutamine was confirmed, but the chronotropic effect was not significantly different from that of isoprenaline. This contrasts with the findings of previous studies, and possible reasons for this are discussed.", "contents": "A comparison of cardiovascular effects of dobutamine and isoprenaline after open heart surgery. In a cross-over study, the cardiovascular effects of dobutamine were assessed in 11 patients who had undergone operation for replacement of the mitral or aortic valve approximately four hours earlier. In 9 of these the effects of isoprenaline were assessed for comparison. Dose-response curves were obtained using four dose levels of dobutamine in the range 1.25-10 mug/kg per min and of isoprenaline in the range of 0.005-0.04 mug/kg per min. Both drugs produced similar dose-dependent increases in heart rate and cardiac output and a dose-dependent decrease in peripheral resistance. Mean arterial pressure was only slightly increased by either drug. The positive inotropic effect of dobutamine was confirmed, but the chronotropic effect was not significantly different from that of isoprenaline. This contrasts with the findings of previous studies, and possible reasons for this are discussed."} {"id": "PMID:1275990", "title": "Echocardiographic diagnosis of left atrial myxoma. Usefulness of suprasternal approach.", "content": "Three cases of left atrial myxoma were studied by echocardiography. In one case the atrial tumour was prolapsing through the mitral orifice into the left ventricular cavity; in the other two cases it was not. The angiocardiographic and operative findings correlated well with those from echocardiography. A systematic echocardiographic study is important; the suprasternal approach is useful in the echocardiographic exploration of the left atriu, especially for nonprolapsing tumours.", "contents": "Echocardiographic diagnosis of left atrial myxoma. Usefulness of suprasternal approach. Three cases of left atrial myxoma were studied by echocardiography. In one case the atrial tumour was prolapsing through the mitral orifice into the left ventricular cavity; in the other two cases it was not. The angiocardiographic and operative findings correlated well with those from echocardiography. A systematic echocardiographic study is important; the suprasternal approach is useful in the echocardiographic exploration of the left atriu, especially for nonprolapsing tumours."} {"id": "PMID:1275991", "title": "Left anterior descending coronary artery obstruction. Clinical, electrocardiographic, and angiographic correlates.", "content": "Seventy-six patients with severe (greater than 80%) occlusive left anterior descending coronary artery disease by coronary angiography were examined for the electrocardiographic characteristics of this disease in the presence (group A 59 patients) or the absence (group B 17 patients) of anterior wall asynergy (akinesis or dyskinesis). The incidence of clinically documented anterior myocardial infarction in these two groups of patients was examined. The collateral circulation to the left anterior descending coronary artery was also examined in the groups of patients with and without anterior wall asynergy. Thirty-eight of 59 (64%) patients with anterior wall asynergy (group A) showed electrocardiographic signs of anterior myocardial infarction, 17 per cent showed probable electrocardiographic signs of anterior myocardial infarction and 19 per cent showed no electrocardiographic signs. None of the 17 patients without anterior wall asynergy (group B) showed electrocardiographic signs of anterior myocardial infarction. In group A 74.6 per cent had documented clinical evidence of previous anterior myocardial infarction. Collateral filling of the distal left anterior descending coronary artery was seen in 71 per cent of group A and 100 per cent of group B patients. There was a significantly higher incidence (P = 0.02) of collateral filling in the patients without electrocardiographic evidence of definite anterior myocardial infarction (93% of 28 patients), than in those who showed definite electrocardiographic evidence of anterior myocardial infarction (66% of 38 patients).it is concluded that severe occlusive left anterior descending coronary artery disease with anterior wall myocardial asynergy is usually associated with electrocardiographic signs of anterior myocardial infarction, whereas equally severe left anterior descending coronary artery disease without anterior wall asynergy is rarely associated with electrocardiographic abnormalities of anterior myocardial infarction. Severe left anterior descending coronary artery obstruction without electrocardiographic and angiographic evidence of anterior myocardial infarction is usually associated with collateral circulation to the left anterior descending coronary artery and collateral circulation to the left anterior descending coronary artery is present less frequently when obstruction is associated with anterior myocardial infarction.", "contents": "Left anterior descending coronary artery obstruction. Clinical, electrocardiographic, and angiographic correlates. Seventy-six patients with severe (greater than 80%) occlusive left anterior descending coronary artery disease by coronary angiography were examined for the electrocardiographic characteristics of this disease in the presence (group A 59 patients) or the absence (group B 17 patients) of anterior wall asynergy (akinesis or dyskinesis). The incidence of clinically documented anterior myocardial infarction in these two groups of patients was examined. The collateral circulation to the left anterior descending coronary artery was also examined in the groups of patients with and without anterior wall asynergy. Thirty-eight of 59 (64%) patients with anterior wall asynergy (group A) showed electrocardiographic signs of anterior myocardial infarction, 17 per cent showed probable electrocardiographic signs of anterior myocardial infarction and 19 per cent showed no electrocardiographic signs. None of the 17 patients without anterior wall asynergy (group B) showed electrocardiographic signs of anterior myocardial infarction. In group A 74.6 per cent had documented clinical evidence of previous anterior myocardial infarction. Collateral filling of the distal left anterior descending coronary artery was seen in 71 per cent of group A and 100 per cent of group B patients. There was a significantly higher incidence (P = 0.02) of collateral filling in the patients without electrocardiographic evidence of definite anterior myocardial infarction (93% of 28 patients), than in those who showed definite electrocardiographic evidence of anterior myocardial infarction (66% of 38 patients).it is concluded that severe occlusive left anterior descending coronary artery disease with anterior wall myocardial asynergy is usually associated with electrocardiographic signs of anterior myocardial infarction, whereas equally severe left anterior descending coronary artery disease without anterior wall asynergy is rarely associated with electrocardiographic abnormalities of anterior myocardial infarction. Severe left anterior descending coronary artery obstruction without electrocardiographic and angiographic evidence of anterior myocardial infarction is usually associated with collateral circulation to the left anterior descending coronary artery and collateral circulation to the left anterior descending coronary artery is present less frequently when obstruction is associated with anterior myocardial infarction."} {"id": "PMID:1275992", "title": "Idiopathic aortitis with calcification of ascending aorta, and aortic and mitral valves.", "content": "A young woman with unexplained radiographic calcification of the ascending aorta was found at necropsy to have healed idiopathic aorititis. Calcification also involved the aortic valve which was stenosed and the mitral valve. Death was the result of infective endocarditis of these valves with aortic ring abscess, rupture of aortic root, and cardiac tamponade.", "contents": "Idiopathic aortitis with calcification of ascending aorta, and aortic and mitral valves. A young woman with unexplained radiographic calcification of the ascending aorta was found at necropsy to have healed idiopathic aorititis. Calcification also involved the aortic valve which was stenosed and the mitral valve. Death was the result of infective endocarditis of these valves with aortic ring abscess, rupture of aortic root, and cardiac tamponade."} {"id": "PMID:1275995", "title": "Pharmacokinetics of halothane in the dog. Comparison of theory and measurement in individuals.", "content": "After surgical preparation under pentobarbitone anaesthesia seven dogs of mean body weight 31 kg were ventilated with 1% halothane for 80 min. At 1, 2, 5, 10, 20, 40 and 80 min after the start of the halothane administration blood samples were taken from the femoral artery and pulmonary artery and from a cerebral, a renal and a femoral vein. At 80 min a biopsy sample of skeletal muscle (psoas) was taken. The halothane tension in all samples was determined by extraction into carbon tetrachloride followed by gas chromatographic analysis using chloroform as an internal standard. The measured tensions were compared with tensions computed from a multi-compartment model of the uptake and distribution of halothane in the body. The model was quantified by measurements, in each individual, of total body mass, the masses of the major organs and the solubility of halothane in the major organs and tissues; by measurements of blood volume and solubility in blood at the start and finish of the halothane administration; and by repeated measurements of alveolar ventilation, cardiac output and body temperature. For the original version of the model, the computed tensions deviated from the measured tensions to an extent greater than could be attributed to experimental error and in a manner which could be attributed to metabolism of halothane and probably to direct diffusion of halothane from well-perfused organs and lean tissues into fat. Direct experimental evidence of diffusion into perirenal fat was obtained in supplementary experiments. With the quantitation of the model distorted to mimic the processes of metabolism and diffusion, measured arterial tensions could be predicted with a mean error of -0.2 mm Hg (SD 0.6 mm Hg). The mean measured arterial tension was 3.5 mm Hg.", "contents": "Pharmacokinetics of halothane in the dog. Comparison of theory and measurement in individuals. After surgical preparation under pentobarbitone anaesthesia seven dogs of mean body weight 31 kg were ventilated with 1% halothane for 80 min. At 1, 2, 5, 10, 20, 40 and 80 min after the start of the halothane administration blood samples were taken from the femoral artery and pulmonary artery and from a cerebral, a renal and a femoral vein. At 80 min a biopsy sample of skeletal muscle (psoas) was taken. The halothane tension in all samples was determined by extraction into carbon tetrachloride followed by gas chromatographic analysis using chloroform as an internal standard. The measured tensions were compared with tensions computed from a multi-compartment model of the uptake and distribution of halothane in the body. The model was quantified by measurements, in each individual, of total body mass, the masses of the major organs and the solubility of halothane in the major organs and tissues; by measurements of blood volume and solubility in blood at the start and finish of the halothane administration; and by repeated measurements of alveolar ventilation, cardiac output and body temperature. For the original version of the model, the computed tensions deviated from the measured tensions to an extent greater than could be attributed to experimental error and in a manner which could be attributed to metabolism of halothane and probably to direct diffusion of halothane from well-perfused organs and lean tissues into fat. Direct experimental evidence of diffusion into perirenal fat was obtained in supplementary experiments. With the quantitation of the model distorted to mimic the processes of metabolism and diffusion, measured arterial tensions could be predicted with a mean error of -0.2 mm Hg (SD 0.6 mm Hg). The mean measured arterial tension was 3.5 mm Hg."} {"id": "PMID:1275996", "title": "Porcine malignant hyperthermia. I: Metabolic and physiological changes.", "content": "Porcine malignant hyperthermia was studied in seven Pietrain pigs under standardized experimental conditions. In five animals malignant hyperthermia was triggered with suxamethonium and halothane, but in two pigs suxamethonium alone was used. Characteristic metabolic and physiological changes were found and these are discussed with regard to a possible mechanism to explain the malignant nature of the syndrome.", "contents": "Porcine malignant hyperthermia. I: Metabolic and physiological changes. Porcine malignant hyperthermia was studied in seven Pietrain pigs under standardized experimental conditions. In five animals malignant hyperthermia was triggered with suxamethonium and halothane, but in two pigs suxamethonium alone was used. Characteristic metabolic and physiological changes were found and these are discussed with regard to a possible mechanism to explain the malignant nature of the syndrome."} {"id": "PMID:1275997", "title": "Porcine malignant hyperthermia. II: Heat production.", "content": "The contributions of aerobic and anaerobic muscle metabolism to the heat produced in porcine malignant hyperthermia were studied in seven Pietrain pigs. Oxygen consumption measurements were used to calculate the increase in muscle temperature as a result of aerobic metabolism and this was compared with the observed muscle temperature. The results show that in the initial stage of porcine malignant hyperthermia heat production is largely aerobic in origin. Terminally, aerobic metabolism can account for about half the observed temperature increase.", "contents": "Porcine malignant hyperthermia. II: Heat production. The contributions of aerobic and anaerobic muscle metabolism to the heat produced in porcine malignant hyperthermia were studied in seven Pietrain pigs. Oxygen consumption measurements were used to calculate the increase in muscle temperature as a result of aerobic metabolism and this was compared with the observed muscle temperature. The results show that in the initial stage of porcine malignant hyperthermia heat production is largely aerobic in origin. Terminally, aerobic metabolism can account for about half the observed temperature increase."} {"id": "PMID:1275998", "title": "Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. I: Halothane dose-response studies.", "content": "The effect of pretreatment for 3 weeks with propranolol 20 mg/kg/day on cardiovascular function during increasing depths of halothane anaesthesia (range 1.0-2.5% inspired halothane with IPPV and normocapnia) were studied in a group of seven closed-chest dogs which had been implanted previously with cardiovascular flow- and pressure-measuring instruments. The results were compared with those observed in a similar group of five untreated dogs. Propranolol pretreatment resulted in a small degree of additional cardiac depression at any inspired halothane concentration. The cardiac depressant effects of propranolol and halothane were found to be simply additive and therefore predictable. The presence of propranolol did not result in morbidity or mortality at any depth of halothane anaesthesia.", "contents": "Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. I: Halothane dose-response studies. The effect of pretreatment for 3 weeks with propranolol 20 mg/kg/day on cardiovascular function during increasing depths of halothane anaesthesia (range 1.0-2.5% inspired halothane with IPPV and normocapnia) were studied in a group of seven closed-chest dogs which had been implanted previously with cardiovascular flow- and pressure-measuring instruments. The results were compared with those observed in a similar group of five untreated dogs. Propranolol pretreatment resulted in a small degree of additional cardiac depression at any inspired halothane concentration. The cardiac depressant effects of propranolol and halothane were found to be simply additive and therefore predictable. The presence of propranolol did not result in morbidity or mortality at any depth of halothane anaesthesia."} {"id": "PMID:1275999", "title": "Effects on ionized calcium of a correction of acidosis with alkalinizing agents. A rational basis for the administration of calcium in cardiac resuscitation.", "content": "The effects on the ionized calcium concentration of a correction of various forms of acidosis with sodium bicarbonate or (tris-hydroxymethyl)aminomethane (THAM) were investigated in vitro in human plasma. Calculation of least square regression equations of ionized calcium (m mol) on pH yielded the following regression coefficients: hydrochloric acidosis: -0.65 +/- 0.06; lactic acidosis: -0.27 +/- 0.05; hydrochloric acidosis corrected with sodium bicarbonate: -0.65 +/- 0.02; lactic acidosis corrected with sodium bicarbonate: -0.51 +/- 0.03. The results indicate that after correction of lactic acidosis the ionized calcium concentration will be below the control values while pH is restored to the normal range. This effect is even more pronounced when THAM is used. The findings point to the need for calcium administration in cardiac resuscitation.", "contents": "Effects on ionized calcium of a correction of acidosis with alkalinizing agents. A rational basis for the administration of calcium in cardiac resuscitation. The effects on the ionized calcium concentration of a correction of various forms of acidosis with sodium bicarbonate or (tris-hydroxymethyl)aminomethane (THAM) were investigated in vitro in human plasma. Calculation of least square regression equations of ionized calcium (m mol) on pH yielded the following regression coefficients: hydrochloric acidosis: -0.65 +/- 0.06; lactic acidosis: -0.27 +/- 0.05; hydrochloric acidosis corrected with sodium bicarbonate: -0.65 +/- 0.02; lactic acidosis corrected with sodium bicarbonate: -0.51 +/- 0.03. The results indicate that after correction of lactic acidosis the ionized calcium concentration will be below the control values while pH is restored to the normal range. This effect is even more pronounced when THAM is used. The findings point to the need for calcium administration in cardiac resuscitation."} {"id": "PMID:1276000", "title": "Pharmacokinetics of pancuronium in patients with normal and impaired renal function.", "content": "Plasma concentrations of pancuronium were measured using a fluorimetric method in six patients with normal renal function and seven patients in chronic renal failure. A tow-compartment open model was used in the pharmacokinetic analysis of the data. With this model, the clearance of pancuronium was found to be reduced significantly in the patients with renal failure, and in these individuals the volume of the central (distribution) compartment was increased significantly. The clinical implications of these findings are discussed.", "contents": "Pharmacokinetics of pancuronium in patients with normal and impaired renal function. Plasma concentrations of pancuronium were measured using a fluorimetric method in six patients with normal renal function and seven patients in chronic renal failure. A tow-compartment open model was used in the pharmacokinetic analysis of the data. With this model, the clearance of pancuronium was found to be reduced significantly in the patients with renal failure, and in these individuals the volume of the central (distribution) compartment was increased significantly. The clinical implications of these findings are discussed."} {"id": "PMID:1276001", "title": "A foreign body in the larynx. A case report.", "content": "A young patient with a head injury inhaled a dental plate 60 hr after injury.", "contents": "A foreign body in the larynx. A case report. A young patient with a head injury inhaled a dental plate 60 hr after injury."} {"id": "PMID:1276002", "title": "Tracheal intubation with a Robertshaw tube via a tracheostomy.", "content": "A patient who had a permanent tracheostomy needed to be anaesthetized for thoracotomy. Anticipated difficulty with airway and lung control did not occur following successful intubation via the tracheostomy with a Robertshaw double-lumen tube.", "contents": "Tracheal intubation with a Robertshaw tube via a tracheostomy. A patient who had a permanent tracheostomy needed to be anaesthetized for thoracotomy. Anticipated difficulty with airway and lung control did not occur following successful intubation via the tracheostomy with a Robertshaw double-lumen tube."} {"id": "PMID:1276003", "title": "Urban mobile resuscitation: training and service.", "content": "The establishment of a Mobile Resuscitation Unit based on a District General Hospital is described. The Unit is manned by hospital-trained ambulance men and by an anaesthetist when necessary. The training of the ambulance men, organization of the service and the results are discussed. The authors recommend the establishment of such a unit in association with an urban district general hospital for the immediate care of all patients who suddenly become seriously ill, regardless of the cause of their illness or accident.", "contents": "Urban mobile resuscitation: training and service. The establishment of a Mobile Resuscitation Unit based on a District General Hospital is described. The Unit is manned by hospital-trained ambulance men and by an anaesthetist when necessary. The training of the ambulance men, organization of the service and the results are discussed. The authors recommend the establishment of such a unit in association with an urban district general hospital for the immediate care of all patients who suddenly become seriously ill, regardless of the cause of their illness or accident."} {"id": "PMID:1276004", "title": "The influence of carrier gas on the output of automatic plenum vaporizers.", "content": "The effect of the physical characteristics of the carrier gas on the output of automatic plenum vaporizers was studied. The Vapor and Fluomatic halothane output at all dial settings was highest with oxygen as the carrier gas, as compared with helium and nitrous oxide and was a function of carrier gas viscosity at all dial settings. The output of the Fluotec Mark 2 at the 0.5 and 1% settings was highest with nitrous oxide as the carrier gas, but at 2, 3 and 4% settings it was highest with oxygen; at the 0.5% and 1% dial settings it was a function of carrier gas density, but at 2%, 3% and 4% it was a function of carrier gas viscosity.", "contents": "The influence of carrier gas on the output of automatic plenum vaporizers. The effect of the physical characteristics of the carrier gas on the output of automatic plenum vaporizers was studied. The Vapor and Fluomatic halothane output at all dial settings was highest with oxygen as the carrier gas, as compared with helium and nitrous oxide and was a function of carrier gas viscosity at all dial settings. The output of the Fluotec Mark 2 at the 0.5 and 1% settings was highest with nitrous oxide as the carrier gas, but at 2, 3 and 4% settings it was highest with oxygen; at the 0.5% and 1% dial settings it was a function of carrier gas density, but at 2%, 3% and 4% it was a function of carrier gas viscosity."} {"id": "PMID:1276012", "title": "Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. II: The effects of acute arterial hypoxaemia at increasing depths of halothane anaesthesia.", "content": "Beta-adrenergic blockade may impair the normal cardiovascular response to hypoxia occurring during general anaesthesia. The haemodynamic effects of acute hypoxia, induced by a 90-s period of ventilation with nitrogen, were studied during increasing depths of halothane anaesthesia up to a maximum of 2.5% inspired halothane in dogs chronically implanted with intracardiac catheters, a left-ventricular pressure transducer and an aortic blood flow transducer. An untreated group of dogs and a group which had been treated for 3 weeks with propranolol 20 mg/kg/day were compared. The beta-blocked group had lesser cardiac output values, left-ventricular contractility indices, external left-ventricular work and peak left-ventricular power at all depths of anaesthesia except 2.5% halothane, but both groups responded to hypoxia similarly at each depth of anaesthesia. Cardiac performance was enhanced in both groups during acute hypoxia. No adverse haemodynamic effect of the combination of propranolol, halothane and hypoxia was demonstrated.", "contents": "Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. II: The effects of acute arterial hypoxaemia at increasing depths of halothane anaesthesia. Beta-adrenergic blockade may impair the normal cardiovascular response to hypoxia occurring during general anaesthesia. The haemodynamic effects of acute hypoxia, induced by a 90-s period of ventilation with nitrogen, were studied during increasing depths of halothane anaesthesia up to a maximum of 2.5% inspired halothane in dogs chronically implanted with intracardiac catheters, a left-ventricular pressure transducer and an aortic blood flow transducer. An untreated group of dogs and a group which had been treated for 3 weeks with propranolol 20 mg/kg/day were compared. The beta-blocked group had lesser cardiac output values, left-ventricular contractility indices, external left-ventricular work and peak left-ventricular power at all depths of anaesthesia except 2.5% halothane, but both groups responded to hypoxia similarly at each depth of anaesthesia. Cardiac performance was enhanced in both groups during acute hypoxia. No adverse haemodynamic effect of the combination of propranolol, halothane and hypoxia was demonstrated."} {"id": "PMID:1276013", "title": "Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. III: The effects of haemorrhage during halothane and trichloroethylene anaesthesia.", "content": "We have examined the haemodynamic effects of 0.8% trichloroethylene and 1% halothane anaesthesia in a control group of five dogs, chronically implanted with cardiovascular flow- and pressure-measuring apparatus and compared them with a similar group of six dogs pretreated for 3 weeks with oral propranolol (20 mg/kg/day). The effects of graded haemorrhage of 25% of the estimated blood volume and re-transfusion were studied. Cardiovascular function was satisfactory at all stages of the study except during trichloroethylene anaesthesia in the beta-blocked dogs when the response to blood loss was impaired severely. Therefore the use of trichloroethylene in the presence of propranolol may not be advisable in clinical practice.", "contents": "Haemodynamic interactions of high-dose propranolol pretreatment and anaesthesia in the dog. III: The effects of haemorrhage during halothane and trichloroethylene anaesthesia. We have examined the haemodynamic effects of 0.8% trichloroethylene and 1% halothane anaesthesia in a control group of five dogs, chronically implanted with cardiovascular flow- and pressure-measuring apparatus and compared them with a similar group of six dogs pretreated for 3 weeks with oral propranolol (20 mg/kg/day). The effects of graded haemorrhage of 25% of the estimated blood volume and re-transfusion were studied. Cardiovascular function was satisfactory at all stages of the study except during trichloroethylene anaesthesia in the beta-blocked dogs when the response to blood loss was impaired severely. Therefore the use of trichloroethylene in the presence of propranolol may not be advisable in clinical practice."} {"id": "PMID:1276014", "title": "Hepatic pathology and skin test reactions to trifluoro-acetylated autologous protein after repeated halothane anaesthesia in the guineapig.", "content": "The aetiology of the rare hepatic failure following halothane anaesthesia is not known. In an attempt to develop an experimental model, three groups of guineapigs were exposed to air or oxygen, a single 1% halothane administration, or five exposures of 1% halothane at weekly intervals. In an attempt to identify a hypersensitivity reaction, all animals were skin-tested with the common final metabolite of halothane, fluroxene and isoflurane: trifluoroacetic acid, prepared as a complex with autologous serum protein. Hepatic necrosis was found in all groups and did not correlate with positive skin reactions. There was an increase in fatty changes in the liver in animals anaesthetized with halothane.", "contents": "Hepatic pathology and skin test reactions to trifluoro-acetylated autologous protein after repeated halothane anaesthesia in the guineapig. The aetiology of the rare hepatic failure following halothane anaesthesia is not known. In an attempt to develop an experimental model, three groups of guineapigs were exposed to air or oxygen, a single 1% halothane administration, or five exposures of 1% halothane at weekly intervals. In an attempt to identify a hypersensitivity reaction, all animals were skin-tested with the common final metabolite of halothane, fluroxene and isoflurane: trifluoroacetic acid, prepared as a complex with autologous serum protein. Hepatic necrosis was found in all groups and did not correlate with positive skin reactions. There was an increase in fatty changes in the liver in animals anaesthetized with halothane."} {"id": "PMID:1276015", "title": "Pain during continuous nitrous oxide administration.", "content": "The continuous administration of nitrous oxide, in subjects who remain conscious, caused only a relatively small increase in the threshold of appreciation of pain, induced experimentally by tibial pressure and a hot wire applied to the thenar eminence. The threshold reached a maximum at 10 min. A concentration of 50% nitrous oxide caused only a marginally greater effect than 33%. In some subjects pain thresholds returned to control values during administration of the gas. In contrast, when a concentration of 50% nitrous oxide was approached in step changes of 7-10% over a period of 45 min, the effect on the pain threshold was more than doubled. It was concluded that, with respect to analgesia, adaptation of the nervous system to a constant concentration of nitrous oxide can occur in some subjects.", "contents": "Pain during continuous nitrous oxide administration. The continuous administration of nitrous oxide, in subjects who remain conscious, caused only a relatively small increase in the threshold of appreciation of pain, induced experimentally by tibial pressure and a hot wire applied to the thenar eminence. The threshold reached a maximum at 10 min. A concentration of 50% nitrous oxide caused only a marginally greater effect than 33%. In some subjects pain thresholds returned to control values during administration of the gas. In contrast, when a concentration of 50% nitrous oxide was approached in step changes of 7-10% over a period of 45 min, the effect on the pain threshold was more than doubled. It was concluded that, with respect to analgesia, adaptation of the nervous system to a constant concentration of nitrous oxide can occur in some subjects."} {"id": "PMID:1276016", "title": "A theoretical study of gaseous homeostasis in the Magill circuit.", "content": "Equations have been derived to determine the alveolar gas concentrations which occur when the Magill (Mapleson A) circuit is used with a low fresh gas flow. Alveolar oxygen and carbon dioxide concentrations are determined by the fresh gas flow and composition, carbon dioxide output and oxygen uptake. Gas mixing within the circuit and alterations in the inspired gas concentrations do not affect the final equilibrium. If oxygen uptake and carbon dioxide output are constant, the alveolar gas concentrations are unaffected by alterations in ventilation.", "contents": "A theoretical study of gaseous homeostasis in the Magill circuit. Equations have been derived to determine the alveolar gas concentrations which occur when the Magill (Mapleson A) circuit is used with a low fresh gas flow. Alveolar oxygen and carbon dioxide concentrations are determined by the fresh gas flow and composition, carbon dioxide output and oxygen uptake. Gas mixing within the circuit and alterations in the inspired gas concentrations do not affect the final equilibrium. If oxygen uptake and carbon dioxide output are constant, the alveolar gas concentrations are unaffected by alterations in ventilation."} {"id": "PMID:1276017", "title": "An experimental study of gaseous homeostasis and the Magill circuit using low fresh gas flows.", "content": "Gas concentrations and ventilation levels have been measured within a conventional Magill circuit when conscious volunteers breathed a non-narcotic gas mixture at varying fresh gas flows. When evidence of rebreathing of alveolar gas was detected, the fresh gas flow was kept constant until a steady state developed. All subjects showed evidence of rebreathing when the fresh gas flow approached the predicted alveolar ventilation levels. A variety of subject-circuit interactions was seen and shown to be precipitated by naturally occurring breath-to-breath variations in ventilation. A single large breath could perturb the system. This could have a temporary effect, when the fresh gas flow was sufficient to wash the increased aliquot of expired carbon dioxide from the circuit. At other times a progressive response occurred as ventilatory stimulation as a result of the increased inspired carbon dioxide concentrations caused alveolar gas to reach the reservoir bag and converted the system behaviour from that of a simple added deadspace to that of a total mixing device. Whilst marked changes occurred commonly in both ventilation and inspired gas concentrations, only slight changes in end-tidal gas concentrations occurred.", "contents": "An experimental study of gaseous homeostasis and the Magill circuit using low fresh gas flows. Gas concentrations and ventilation levels have been measured within a conventional Magill circuit when conscious volunteers breathed a non-narcotic gas mixture at varying fresh gas flows. When evidence of rebreathing of alveolar gas was detected, the fresh gas flow was kept constant until a steady state developed. All subjects showed evidence of rebreathing when the fresh gas flow approached the predicted alveolar ventilation levels. A variety of subject-circuit interactions was seen and shown to be precipitated by naturally occurring breath-to-breath variations in ventilation. A single large breath could perturb the system. This could have a temporary effect, when the fresh gas flow was sufficient to wash the increased aliquot of expired carbon dioxide from the circuit. At other times a progressive response occurred as ventilatory stimulation as a result of the increased inspired carbon dioxide concentrations caused alveolar gas to reach the reservoir bag and converted the system behaviour from that of a simple added deadspace to that of a total mixing device. Whilst marked changes occurred commonly in both ventilation and inspired gas concentrations, only slight changes in end-tidal gas concentrations occurred."} {"id": "PMID:1276018", "title": "Identification and quantitation of hypersensitivity reactions to intravenous anaesthetic agents.", "content": "It is not possible to distinguish between direct pharmacological effects and immune-mediated hypersensitivity reactions by clinical observation alone and errors may occur in the absence of laboratory tests. A convenient and simple test is the measurement of plasma complement C3 consumption and conversion in sequential blood samples taken at intervals over the 24 h following an adverse response.", "contents": "Identification and quantitation of hypersensitivity reactions to intravenous anaesthetic agents. It is not possible to distinguish between direct pharmacological effects and immune-mediated hypersensitivity reactions by clinical observation alone and errors may occur in the absence of laboratory tests. A convenient and simple test is the measurement of plasma complement C3 consumption and conversion in sequential blood samples taken at intervals over the 24 h following an adverse response."} {"id": "PMID:1276019", "title": "Alterations in response to somatic pain associated with anaesthesia. XXIII: Further study of naloxone.", "content": "Tibial pressure analgesimetry has been employed to study the antagonistic effects of small doses of naloxone in pethidine-induced analgesia. The dose of pethidine was 100 mg and the doses of naloxone 0.2, 0.1, 0.05 and 0.025 mg/60 kg body weight, and all drugs were given i.v. These doses of naloxone reduced the analgesia produced by pethidine and the degree of antagonism was probably dose-related. It was also found that naloxone antagonized the side-effects of pethidine, especially nausea.", "contents": "Alterations in response to somatic pain associated with anaesthesia. XXIII: Further study of naloxone. Tibial pressure analgesimetry has been employed to study the antagonistic effects of small doses of naloxone in pethidine-induced analgesia. The dose of pethidine was 100 mg and the doses of naloxone 0.2, 0.1, 0.05 and 0.025 mg/60 kg body weight, and all drugs were given i.v. These doses of naloxone reduced the analgesia produced by pethidine and the degree of antagonism was probably dose-related. It was also found that naloxone antagonized the side-effects of pethidine, especially nausea."} {"id": "PMID:1276020", "title": "A possible means of rapid cooling in the emergency treatment of malignant hyperpyrexia.", "content": "A possible means of rapid cooling in the emergency treatment of malignant hyperpyrexia, peritoneal dialysis using a cold dialysate, is described. Experimental observations in a young man on a regular peritoneal dialysis regime showed that significant heat extraction can be obtained when either a cool (20 degrees C) or cold (9 degrees C) dialysis fluid is used. The maximum heat exchange observed was 17.5 kJ/min when 2 litre of cold dialysis was instilled for a mean time of 10 min. This rate of heat exchange is within the 10--40 kJ/min range of excess heat production that occurs in malignant hyperpyrexia. Since peritoneal dialysis is, technically, a very quick and simple procedure, it is suggested that it might play a very useful role in the emergency treatment of malignant hyperpyrexia. The dialysis treatment would also correct some of the biochemical disturbances that occur in this condition.", "contents": "A possible means of rapid cooling in the emergency treatment of malignant hyperpyrexia. A possible means of rapid cooling in the emergency treatment of malignant hyperpyrexia, peritoneal dialysis using a cold dialysate, is described. Experimental observations in a young man on a regular peritoneal dialysis regime showed that significant heat extraction can be obtained when either a cool (20 degrees C) or cold (9 degrees C) dialysis fluid is used. The maximum heat exchange observed was 17.5 kJ/min when 2 litre of cold dialysis was instilled for a mean time of 10 min. This rate of heat exchange is within the 10--40 kJ/min range of excess heat production that occurs in malignant hyperpyrexia. Since peritoneal dialysis is, technically, a very quick and simple procedure, it is suggested that it might play a very useful role in the emergency treatment of malignant hyperpyrexia. The dialysis treatment would also correct some of the biochemical disturbances that occur in this condition."} {"id": "PMID:1276021", "title": "A comparison of oesophageal and central venous pressures in the measurement of transpulmonary pressure change.", "content": "Oesophageal (oes) and central venous pressure (CVP) were compared as indices of transpulmonary pressure change (deltap). The mean increase of deltaPoes over deltapCVP was 2.8 cm H2O. The size and variability of the increase were similar to the expected difference between oesophageal and pleural pressure fluctuations occurring in the supine patient. Central venous pressure may be more accurate and reliable than oesophageal pressure for estimations of transpulmonary pressure change in the supine position.", "contents": "A comparison of oesophageal and central venous pressures in the measurement of transpulmonary pressure change. Oesophageal (oes) and central venous pressure (CVP) were compared as indices of transpulmonary pressure change (deltap). The mean increase of deltaPoes over deltapCVP was 2.8 cm H2O. The size and variability of the increase were similar to the expected difference between oesophageal and pleural pressure fluctuations occurring in the supine patient. Central venous pressure may be more accurate and reliable than oesophageal pressure for estimations of transpulmonary pressure change in the supine position."} {"id": "PMID:1276022", "title": "Foetal bradycardia during caudal analgesia: A discussion of possible causative factors.", "content": "A 31-year-old female had caudal analgesia during labour, using 0.5% bupivacaine. Nine minutes after the block, the foetus developed severe bradycardia which lasted for 9 min but recovered spontaneously. Thereafter the foetal heart rate was within the normal range until the end of labour when variable decreases in rate occurred, suggesting cord compression. At the time of delivery there was a knot of the umbilical cord which was also forming a loop around the neck of the baby. There was no abnormality of the Apgar scores or blood-gases in the baby; the plasma bupivacaine concentrations in both mother and child were within the expected range. The possible causative factors for this bradycardia are explained.", "contents": "Foetal bradycardia during caudal analgesia: A discussion of possible causative factors. A 31-year-old female had caudal analgesia during labour, using 0.5% bupivacaine. Nine minutes after the block, the foetus developed severe bradycardia which lasted for 9 min but recovered spontaneously. Thereafter the foetal heart rate was within the normal range until the end of labour when variable decreases in rate occurred, suggesting cord compression. At the time of delivery there was a knot of the umbilical cord which was also forming a loop around the neck of the baby. There was no abnormality of the Apgar scores or blood-gases in the baby; the plasma bupivacaine concentrations in both mother and child were within the expected range. The possible causative factors for this bradycardia are explained."} {"id": "PMID:1276023", "title": "Intravenous regional anaesthesia in children.", "content": "Fifty children, aged 3-12 yr, received intravenous regional anaesthesia for the treatment of either simple forearm fractures or elbow injuries. The technique obviated delays in treatment and allowed the child to be discharged from hospital immediately after treatment. There were no complications resulting from anaesthesia, but there was one anaesthetic failure.", "contents": "Intravenous regional anaesthesia in children. Fifty children, aged 3-12 yr, received intravenous regional anaesthesia for the treatment of either simple forearm fractures or elbow injuries. The technique obviated delays in treatment and allowed the child to be discharged from hospital immediately after treatment. There were no complications resulting from anaesthesia, but there was one anaesthetic failure."} {"id": "PMID:1276024", "title": "Towards blood-gas autoanalysis an evaluation of the radiometer ABL.", "content": "The performance of the Radiometer ABL 1 blood-gas analyser has been evaluated using tonometered blood samples of known PO2 and PCO2. The pH electrode was compared with two other pH electrode systems and the haemoglobin estimations were compared with measurements made by the standard cyanmethaemoglobin method. The accuracy of the machine compared well with standard blood-gas equipment, but the haemoglobin values had a small error because of a zero offset in the machine. The analyzer is simple to operate and has low running costs.", "contents": "Towards blood-gas autoanalysis an evaluation of the radiometer ABL. The performance of the Radiometer ABL 1 blood-gas analyser has been evaluated using tonometered blood samples of known PO2 and PCO2. The pH electrode was compared with two other pH electrode systems and the haemoglobin estimations were compared with measurements made by the standard cyanmethaemoglobin method. The accuracy of the machine compared well with standard blood-gas equipment, but the haemoglobin values had a small error because of a zero offset in the machine. The analyzer is simple to operate and has low running costs."} {"id": "PMID:1276030", "title": "Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells.", "content": "The cytocidal properties of metronidazole against hypoxic mammalian cells are described. This chemotherapeutic action has been shown to be dependent on drug concentration and duration of exposure. The x-ray TCD50 for a murine anaplastic carcinoma was reduced from 6081 rad to 4643 rad when animals were given metronidazole orally for 36 h before radiation treatment. The effect is attributed to the direct killing of hypoxic tumour cells by a mechanism analogous to that proposed for the action of the drug on anaerobic micro-organisms. It is concluded that further work with metronidazole as a cytotoxin specific for hypoxic cells is warranted, particularly in view of the reported lack of toxicity associated with the preliminary clinical use of the drug as a radiosensitizer in man.", "contents": "Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells. The cytocidal properties of metronidazole against hypoxic mammalian cells are described. This chemotherapeutic action has been shown to be dependent on drug concentration and duration of exposure. The x-ray TCD50 for a murine anaplastic carcinoma was reduced from 6081 rad to 4643 rad when animals were given metronidazole orally for 36 h before radiation treatment. The effect is attributed to the direct killing of hypoxic tumour cells by a mechanism analogous to that proposed for the action of the drug on anaerobic micro-organisms. It is concluded that further work with metronidazole as a cytotoxin specific for hypoxic cells is warranted, particularly in view of the reported lack of toxicity associated with the preliminary clinical use of the drug as a radiosensitizer in man."} {"id": "PMID:1276031", "title": "Effect of C. Parvum on immunization with irradiated tumour cells.", "content": "S.c. injection of tumour cells or small pieces of tumour irradiated to a dose of 22,000 rad evoked resistance to live challenge with the same tumour (a CBA strain fibrosarcoma induced with methylcholanthrene) 14 days later. This resistance was, however, over-ridden if the challenging inoculum was sufficiently large, and did not develop if the cells were irradiated to 100,000 rad. The resistance evoked by injection of 10(6) irradiated tumour cells was impaired by i.p. injection of 1-4 mg C. parvum 5 days before, and virtually abolished by a similar injection 11 days after, the irradiated cells. The effect of s.c. injection of a mixture of 10(6) irradiated cells and C. parvum 14 days before live challenge depended on the dose of C. parvum. With 0-7 mg the development of resistance was largely but not completely abrogated; 0-35 mg resulted in a lesser degree of abrogation, and 0-09 mg or 0-02 mg had little or no effect.", "contents": "Effect of C. Parvum on immunization with irradiated tumour cells. S.c. injection of tumour cells or small pieces of tumour irradiated to a dose of 22,000 rad evoked resistance to live challenge with the same tumour (a CBA strain fibrosarcoma induced with methylcholanthrene) 14 days later. This resistance was, however, over-ridden if the challenging inoculum was sufficiently large, and did not develop if the cells were irradiated to 100,000 rad. The resistance evoked by injection of 10(6) irradiated tumour cells was impaired by i.p. injection of 1-4 mg C. parvum 5 days before, and virtually abolished by a similar injection 11 days after, the irradiated cells. The effect of s.c. injection of a mixture of 10(6) irradiated cells and C. parvum 14 days before live challenge depended on the dose of C. parvum. With 0-7 mg the development of resistance was largely but not completely abrogated; 0-35 mg resulted in a lesser degree of abrogation, and 0-09 mg or 0-02 mg had little or no effect."} {"id": "PMID:1276032", "title": "Changes in the structuredness of cytoplasmic matrix (SCM) in human lymphocytes induced by PHA and cancer basic protein as measured in single cells.", "content": "The method of measuring changes in the structuredness of cytoplasmic matrix (SCM) in single cells is described. Data on SCM distributions and fractions of human lymphocyte populations which respond to stimulations with PHA and CaBP in healthy donors and patients with malignant disorders are presented.", "contents": "Changes in the structuredness of cytoplasmic matrix (SCM) in human lymphocytes induced by PHA and cancer basic protein as measured in single cells. The method of measuring changes in the structuredness of cytoplasmic matrix (SCM) in single cells is described. Data on SCM distributions and fractions of human lymphocyte populations which respond to stimulations with PHA and CaBP in healthy donors and patients with malignant disorders are presented."} {"id": "PMID:1276033", "title": "Incidence of oral leucoplakias among 20,358 Indian villagers in a 7-year period.", "content": "A group of 20,358 villagers in two districts of India has been followed for 7 years to study the incidence of oral leucoplakia. The follow-up rate of the population in two districts ranged from 61% to 71%. In one of the districts (Bhavnagar) no new cases of leucoplakia were found among females in the 7-year period. Among males 105 cases developed (4-0/1000/year). The incidence was highest among hookli (clay pipe) smokers. In the Ernakulam district the incidence among males was 3-3/1000/year whereas among females it was 1-9/1000/year. The mixed habits group had the highest incidence of oral leucoplakias (7-2 and 9-9/1000/year among males and females respectively).", "contents": "Incidence of oral leucoplakias among 20,358 Indian villagers in a 7-year period. A group of 20,358 villagers in two districts of India has been followed for 7 years to study the incidence of oral leucoplakia. The follow-up rate of the population in two districts ranged from 61% to 71%. In one of the districts (Bhavnagar) no new cases of leucoplakia were found among females in the 7-year period. Among males 105 cases developed (4-0/1000/year). The incidence was highest among hookli (clay pipe) smokers. In the Ernakulam district the incidence among males was 3-3/1000/year whereas among females it was 1-9/1000/year. The mixed habits group had the highest incidence of oral leucoplakias (7-2 and 9-9/1000/year among males and females respectively)."} {"id": "PMID:1276034", "title": "Childhood Kaposi's sarcoma: clinical features and therapy.", "content": "Twelve cases of childhood Kaposi's sarcoma seen at the Uganda Cancer Institute over the last 7 years are reported. The disease presents mainly as generalized lymphadenopathy, with sparsely and anomalously distributed cutaneous nodules, and has a higher proportion of females with the disease than in the adult form. The histology is usually of mixed cell type. If not treated, childhood Kaposi's sarcoma runs a fulminating course, but disease control with chemotherapy is associated with prolonged survival.", "contents": "Childhood Kaposi's sarcoma: clinical features and therapy. Twelve cases of childhood Kaposi's sarcoma seen at the Uganda Cancer Institute over the last 7 years are reported. The disease presents mainly as generalized lymphadenopathy, with sparsely and anomalously distributed cutaneous nodules, and has a higher proportion of females with the disease than in the adult form. The histology is usually of mixed cell type. If not treated, childhood Kaposi's sarcoma runs a fulminating course, but disease control with chemotherapy is associated with prolonged survival."} {"id": "PMID:1276079", "title": "Disseminated intravascular coagulation caused by the carpet viper (Echis carinatus): trial of heparin.", "content": "Heparin has been advocated for the treatment of poisoning by Echis carinatus, a snake whose venom causes disseminated intravascular coagulation. Fourteen patients with proven E. carinatus bite who had incoagulable blood were treated with specific Echis antivenom. Seven of them were also given low-dose heparin, initially 50 units/kg body weight by i.v. injection, followed by 10 units/kg/h by i.v. infusion for 22 h. Response to treatment was assessed clinically and by repeated tests of blood coagulation. All patients showed a rapid return to normal blood coagulability after treatment and the heparinized group were not significantly different in any respect from the group given antivenom alone. Heparin did not reduce the local effects of envenoming. There appears to be no place for heparin in the treatment of E. carinatus poisoning provided that potent antivenom is available. The in vivo results were supported by in vitro studies in which it was found that Echis-induced thrombin was less sensitive to the inhibitory effect of heparin than physiological thrombin.", "contents": "Disseminated intravascular coagulation caused by the carpet viper (Echis carinatus): trial of heparin. Heparin has been advocated for the treatment of poisoning by Echis carinatus, a snake whose venom causes disseminated intravascular coagulation. Fourteen patients with proven E. carinatus bite who had incoagulable blood were treated with specific Echis antivenom. Seven of them were also given low-dose heparin, initially 50 units/kg body weight by i.v. injection, followed by 10 units/kg/h by i.v. infusion for 22 h. Response to treatment was assessed clinically and by repeated tests of blood coagulation. All patients showed a rapid return to normal blood coagulability after treatment and the heparinized group were not significantly different in any respect from the group given antivenom alone. Heparin did not reduce the local effects of envenoming. There appears to be no place for heparin in the treatment of E. carinatus poisoning provided that potent antivenom is available. The in vivo results were supported by in vitro studies in which it was found that Echis-induced thrombin was less sensitive to the inhibitory effect of heparin than physiological thrombin."} {"id": "PMID:1276080", "title": "Haemolytic anaemia due to glucose-6-phosphate dehydrogenase (G6PD) deficiency: demonstration of two new biochemical variants, G6PD Hamm and G6PD Tarsus.", "content": "Two new variants of erythrocytic glucose-6-phosphate dehydrogenase have been found in one German patient and in another patient of Turkish origin. The enzymes were partially purified 165-fold and 111-fold respectively. Both revealed reduced activity, increased thermolability and a pH-optimum in the alkaline region (8.5 and 9.0). One variant (G6PD Hamm) had a low Km-value for glucose-6-phosphate, the other (G6PD Tarsus) exhibited an increased affinity for glucose-6-phosphate and a reduced affinity for NADP+. This enzyme showed an increased inhibitor constant for NADPH with respect to NADP+. Electrophoretic mobility was normal in both cases. 2-Desoxy glucose-6-phosphate was utilized to an increased rate by both variant enzymes (46% and 33%). Also galactose-6-phosphate (29% and 25%) and deamino-NADP+ (230% and 261%) gave increased utilization rates. The mothers of both patients could be identified as heterozygous for this enzyme deficiency.", "contents": "Haemolytic anaemia due to glucose-6-phosphate dehydrogenase (G6PD) deficiency: demonstration of two new biochemical variants, G6PD Hamm and G6PD Tarsus. Two new variants of erythrocytic glucose-6-phosphate dehydrogenase have been found in one German patient and in another patient of Turkish origin. The enzymes were partially purified 165-fold and 111-fold respectively. Both revealed reduced activity, increased thermolability and a pH-optimum in the alkaline region (8.5 and 9.0). One variant (G6PD Hamm) had a low Km-value for glucose-6-phosphate, the other (G6PD Tarsus) exhibited an increased affinity for glucose-6-phosphate and a reduced affinity for NADP+. This enzyme showed an increased inhibitor constant for NADPH with respect to NADP+. Electrophoretic mobility was normal in both cases. 2-Desoxy glucose-6-phosphate was utilized to an increased rate by both variant enzymes (46% and 33%). Also galactose-6-phosphate (29% and 25%) and deamino-NADP+ (230% and 261%) gave increased utilization rates. The mothers of both patients could be identified as heterozygous for this enzyme deficiency."} {"id": "PMID:1276081", "title": "The role of disulphide bonds in Heinz body attachment to membranes.", "content": "The mechanism of binding of oxidant-induced Heinz bodies to red cell membrane was studied. Heinz bodies induced by acetylphenylhydrazine in intact cells or in the presence of membrane remained attached to membrane when separated by a sucrose gradient. Incubation with sulphydryl reagents failed to free intact Heinz bodies from or prevent attachment to membranes, although the amount of haem was reduced. Thus disulphide bonds do not appear to be a major mechanism of attachment of Heinz bodies to red cell membrane.", "contents": "The role of disulphide bonds in Heinz body attachment to membranes. The mechanism of binding of oxidant-induced Heinz bodies to red cell membrane was studied. Heinz bodies induced by acetylphenylhydrazine in intact cells or in the presence of membrane remained attached to membrane when separated by a sucrose gradient. Incubation with sulphydryl reagents failed to free intact Heinz bodies from or prevent attachment to membranes, although the amount of haem was reduced. Thus disulphide bonds do not appear to be a major mechanism of attachment of Heinz bodies to red cell membrane."} {"id": "PMID:1276082", "title": "The effects of acute bleeding on acid-base balance erythropoietin (Ep) production and in vivo P50 in the rat.", "content": "The mechanism of erythropoietin (Ep) production after acute haemorrhage has been thought to be due to a reduction in blood volume and tissue perfusion leading to tissue hypoxia. In the present study we have evaluated the effect of acute haemorrhage in the rat on the acid-base status, the red cell affinity for oxygen in vivo, and Ep production. Within a few hours after acute blood loss there was a respiratory alkalosis with an increase in blood pH, a decrease in pCO2 and an increase in the red cell affinity of Hb for oxygen in vivo that was temporally related to an increase in Ep production. Within 24 h after the acute haemorrhage, the blood pH AND PCO2, red cell affinity for oxygen in vivo, and Ep level returned towards normal. The decrease in in vivo red cell affinity for oxygen was associated with an increase in red cell 2,3-DPG levels and a decrease in Ep production.", "contents": "The effects of acute bleeding on acid-base balance erythropoietin (Ep) production and in vivo P50 in the rat. The mechanism of erythropoietin (Ep) production after acute haemorrhage has been thought to be due to a reduction in blood volume and tissue perfusion leading to tissue hypoxia. In the present study we have evaluated the effect of acute haemorrhage in the rat on the acid-base status, the red cell affinity for oxygen in vivo, and Ep production. Within a few hours after acute blood loss there was a respiratory alkalosis with an increase in blood pH, a decrease in pCO2 and an increase in the red cell affinity of Hb for oxygen in vivo that was temporally related to an increase in Ep production. Within 24 h after the acute haemorrhage, the blood pH AND PCO2, red cell affinity for oxygen in vivo, and Ep level returned towards normal. The decrease in in vivo red cell affinity for oxygen was associated with an increase in red cell 2,3-DPG levels and a decrease in Ep production."} {"id": "PMID:1276083", "title": "Haemopoietic progenitor cells in prenatal congenitally anaemic 'flexed-tailed' (f/f) mice.", "content": "The incidences of erythroid colony forming cells (CFUe) and granulocyte-macrophage colony forming cells (CFUc) have been measured in 11-18 d prenatal livers of mice of genotype f/f and nearly congenic +/+ controls. In normal fetal livers numbers of CFUe (cells able to form colonies of 16 or more cells after 72 h in vitro) rise to a maximum on day 14 of gestation and represent c 1% of total fetal liver cells. In f/f fetal livers, peak values for numbers and proportions of CFUe are 50% of normal. The f/f lesion does not reduce the numbers of CFUc in fetal liver. Since this deficiency in CFUe parallels deficiencies of similar magnitude in spleen-colony forming units (CFUs) and erythroblasts in the liver, and erythrocytes in the blood, of f/f fetuses it is concluded that the f/f lesion is expressed at an early stage of haemopoietic development in prenatal life. The possibility that restricted haem synthesis is the primary effect of the f/f genotype and responsible for disturbances of both haemopoietic cellular proliferation and haemoglobin synthesis is examined.", "contents": "Haemopoietic progenitor cells in prenatal congenitally anaemic 'flexed-tailed' (f/f) mice. The incidences of erythroid colony forming cells (CFUe) and granulocyte-macrophage colony forming cells (CFUc) have been measured in 11-18 d prenatal livers of mice of genotype f/f and nearly congenic +/+ controls. In normal fetal livers numbers of CFUe (cells able to form colonies of 16 or more cells after 72 h in vitro) rise to a maximum on day 14 of gestation and represent c 1% of total fetal liver cells. In f/f fetal livers, peak values for numbers and proportions of CFUe are 50% of normal. The f/f lesion does not reduce the numbers of CFUc in fetal liver. Since this deficiency in CFUe parallels deficiencies of similar magnitude in spleen-colony forming units (CFUs) and erythroblasts in the liver, and erythrocytes in the blood, of f/f fetuses it is concluded that the f/f lesion is expressed at an early stage of haemopoietic development in prenatal life. The possibility that restricted haem synthesis is the primary effect of the f/f genotype and responsible for disturbances of both haemopoietic cellular proliferation and haemoglobin synthesis is examined."} {"id": "PMID:1276084", "title": "Control of haemopoietic stem cell proliferation by cells in DNA synthesis.", "content": "It has been demonstrated that for the slowly proliferating population of the haemopoietic pluripotent stem cells (CFUs) the response after damage by hydroxyurea to cells synthesizing DNA differs from that after damage by colchicine to cells entering mitosis. The killing of DNA synthesizing cells elicits increased proliferation in the CFUs population. From this it has been inferred that cells in the S phase may inhibit the entry of nonproliferating GO cells into the cell cycle and in this way control cellular proliferation.", "contents": "Control of haemopoietic stem cell proliferation by cells in DNA synthesis. It has been demonstrated that for the slowly proliferating population of the haemopoietic pluripotent stem cells (CFUs) the response after damage by hydroxyurea to cells synthesizing DNA differs from that after damage by colchicine to cells entering mitosis. The killing of DNA synthesizing cells elicits increased proliferation in the CFUs population. From this it has been inferred that cells in the S phase may inhibit the entry of nonproliferating GO cells into the cell cycle and in this way control cellular proliferation."} {"id": "PMID:1276085", "title": "In vivo plasma and urine folate binding after ingestation of 3H-folic acid and 14C-methyl-folate.", "content": "After simultaneous ingestion of equivalent amounts of [3H]folic acid (3H-PteGlu) and [14C]N5-methyl-tetrahydrofolic acid (14C-CH3-H4PteGlu) we were able to demonstrate progressive macromolecular binding of radiofolate in plasma, which appeared to be near maximal at 6 h. Bound radiofolate was predominantly of 14C-CH3H4PteGlu origin, and only at 24 h could 3H incorporation be demonstrated. The binder eluted with albumin from Sephadex DEAE-A50 columns. In urine a smaller bound radiofolate fraction, with approximately equal amounts of 3H and 14C, appeared after 5.5 h. Plasma chromatography showed radio-PteGlu (peak 1) to be rapidly converted to CH3-H4PteGlu (peak 2), with subsequent appearance of two further radiofolate peaks (peaks 3 and 4) the nature of which is as yet unclear. Urine showed similarly placed fractions but their magnitude differed, and urinary peak 3 in particular was much more prominent than its plasma counterpart.", "contents": "In vivo plasma and urine folate binding after ingestation of 3H-folic acid and 14C-methyl-folate. After simultaneous ingestion of equivalent amounts of [3H]folic acid (3H-PteGlu) and [14C]N5-methyl-tetrahydrofolic acid (14C-CH3-H4PteGlu) we were able to demonstrate progressive macromolecular binding of radiofolate in plasma, which appeared to be near maximal at 6 h. Bound radiofolate was predominantly of 14C-CH3H4PteGlu origin, and only at 24 h could 3H incorporation be demonstrated. The binder eluted with albumin from Sephadex DEAE-A50 columns. In urine a smaller bound radiofolate fraction, with approximately equal amounts of 3H and 14C, appeared after 5.5 h. Plasma chromatography showed radio-PteGlu (peak 1) to be rapidly converted to CH3-H4PteGlu (peak 2), with subsequent appearance of two further radiofolate peaks (peaks 3 and 4) the nature of which is as yet unclear. Urine showed similarly placed fractions but their magnitude differed, and urinary peak 3 in particular was much more prominent than its plasma counterpart."} {"id": "PMID:1276086", "title": "Patterns of food iron absorption in iron-deficient white and indian subjects and in venesected haemochromatotic patients.", "content": "The absorption of radioactive iron from a solution of ferrous ascorbate, and from a standard meal containing intrinsically labelled haemoglobin and wheat, was measured in 12 Indian housewives, 18 white hospital patients and 12 subjects with idiopathic haemochromatosis. Eight of the latter had been fully treated by multiple venesections, so that their serum ferritin concentrations were below 25 mug/1. Since the serum ferritin concentrations of the housewives and the hospital patients were comparable, their body iron stores were considered to be depleted to a similar degree. There were no significant differences between the absorptions of ferrous ascorbate or of the haem iron in the standard meal by each group, but the housewives and the hospital patients absorbed significantly less of the non-haem food iron. The mean non-haem food iron absorptions were 36.4%, 5.8% and 18.9% for the treated haemochromatotic subjects, the Indian housewives and the white hospital patients respectively. The discrepancies between the absorptions of the different forms of food iron were highlighted by calculating the ratios between them. The mean non-haem: haem food iron absorption ratio for the group of treated haemochromatotic subjects was 0.98, and for the Indian housewives only 0.18. The white hospital patients did not form a homogenous population: the ratios of the five males and three of the females were greater than 1.0, whereas those of the remaining 10 females were less than 0.5. The results of this study suggest that mal-absorption of non-haem iron from a meal containing bread, presumably due to a defect at the luminal level, may be an important factor in the pathogenesis of iron deficiency in some subjects. The abnormality appears to be particularly prevalent among Indian women living in Durban.", "contents": "Patterns of food iron absorption in iron-deficient white and indian subjects and in venesected haemochromatotic patients. The absorption of radioactive iron from a solution of ferrous ascorbate, and from a standard meal containing intrinsically labelled haemoglobin and wheat, was measured in 12 Indian housewives, 18 white hospital patients and 12 subjects with idiopathic haemochromatosis. Eight of the latter had been fully treated by multiple venesections, so that their serum ferritin concentrations were below 25 mug/1. Since the serum ferritin concentrations of the housewives and the hospital patients were comparable, their body iron stores were considered to be depleted to a similar degree. There were no significant differences between the absorptions of ferrous ascorbate or of the haem iron in the standard meal by each group, but the housewives and the hospital patients absorbed significantly less of the non-haem food iron. The mean non-haem food iron absorptions were 36.4%, 5.8% and 18.9% for the treated haemochromatotic subjects, the Indian housewives and the white hospital patients respectively. The discrepancies between the absorptions of the different forms of food iron were highlighted by calculating the ratios between them. The mean non-haem: haem food iron absorption ratio for the group of treated haemochromatotic subjects was 0.98, and for the Indian housewives only 0.18. The white hospital patients did not form a homogenous population: the ratios of the five males and three of the females were greater than 1.0, whereas those of the remaining 10 females were less than 0.5. The results of this study suggest that mal-absorption of non-haem iron from a meal containing bread, presumably due to a defect at the luminal level, may be an important factor in the pathogenesis of iron deficiency in some subjects. The abnormality appears to be particularly prevalent among Indian women living in Durban."} {"id": "PMID:1276087", "title": "The abundance of ferritin in yolk-sac derived red blood cells of the embryonic mouse.", "content": "Circulating red blood cells formed early in development have several distinctive properties which include retention of the nucleus (mammals), large size and characteristic haemoglobin type (mammals, birds, amphibia). The primitive or embryonic red cells of early development are replaced by the definitive red cells which contain fetal or adult haemoglobin; a second developmental change occurs in the haemoglobin of some mammals (man, cattle, sheep) but does not involve a cell replacement. Circulating yolk-sac derived red cells from embryonic mice are siderocytes; elevated ferritin levels are associated with the circulating red cells of bullfrog tadpoles, but not with those of the adult frog, again indicating that red cell iron metabolism can change during development. In order to extend the observations made on an amphibian to a mammal, the ferritin content of circulating red cells from embryonic mice was determined and found to be 0.65 mg/100 mg of soluble protein; no ferritin (less than or equal to 0.007 mg/100 mg of soluble protein) was detected in adult mouse red cells. Elevated ferritin levels appeared to be specifically associated with the yolk-sac derived population of red cells since a decline in red-cell ferritin content coincided with the replacement of yolk-sac derived red cells by definitive red cells derived from the liver. Fractionation of mixtures of yolk-sac derived and liver derived red cells showed that fractions rich in the definitive red cells contained less ferritin than the mixture. The results suggest that elevated ferritin levels may be a general characteristic of the circulating, haemoglobinized red cells formed early in development.", "contents": "The abundance of ferritin in yolk-sac derived red blood cells of the embryonic mouse. Circulating red blood cells formed early in development have several distinctive properties which include retention of the nucleus (mammals), large size and characteristic haemoglobin type (mammals, birds, amphibia). The primitive or embryonic red cells of early development are replaced by the definitive red cells which contain fetal or adult haemoglobin; a second developmental change occurs in the haemoglobin of some mammals (man, cattle, sheep) but does not involve a cell replacement. Circulating yolk-sac derived red cells from embryonic mice are siderocytes; elevated ferritin levels are associated with the circulating red cells of bullfrog tadpoles, but not with those of the adult frog, again indicating that red cell iron metabolism can change during development. In order to extend the observations made on an amphibian to a mammal, the ferritin content of circulating red cells from embryonic mice was determined and found to be 0.65 mg/100 mg of soluble protein; no ferritin (less than or equal to 0.007 mg/100 mg of soluble protein) was detected in adult mouse red cells. Elevated ferritin levels appeared to be specifically associated with the yolk-sac derived population of red cells since a decline in red-cell ferritin content coincided with the replacement of yolk-sac derived red cells by definitive red cells derived from the liver. Fractionation of mixtures of yolk-sac derived and liver derived red cells showed that fractions rich in the definitive red cells contained less ferritin than the mixture. The results suggest that elevated ferritin levels may be a general characteristic of the circulating, haemoglobinized red cells formed early in development."} {"id": "PMID:1276088", "title": "Absorption of cumene through the respiratory tract and excretion of dimethylphenylcarbinol in urine.", "content": "Experiments on the absorption of cumene and the excretion of dimethylphenylcarbinol were made on 10 healthy volunteers, five men and five women aged between 20 and 35 years. They were exposed to cumene vapours 240, 480, 720 mg/m3 under controlled conditions. It was found that the average retention of cumene vapours was about 50% which tended to diminish at the end of each exposure. Based on these results, an exposure test that allows one to calculate the absorbed cumene dose during eight hours' work with a precision of about +/- 13.5% was achieved.", "contents": "Absorption of cumene through the respiratory tract and excretion of dimethylphenylcarbinol in urine. Experiments on the absorption of cumene and the excretion of dimethylphenylcarbinol were made on 10 healthy volunteers, five men and five women aged between 20 and 35 years. They were exposed to cumene vapours 240, 480, 720 mg/m3 under controlled conditions. It was found that the average retention of cumene vapours was about 50% which tended to diminish at the end of each exposure. Based on these results, an exposure test that allows one to calculate the absorbed cumene dose during eight hours' work with a precision of about +/- 13.5% was achieved."} {"id": "PMID:1276089", "title": "Ostwald solubility coefficients of some industrially important substances.", "content": "Solubility coefficients in blood for benzene, toluene, and xylene were determined as 6.5, 16, and 42 respectively. In lard and olive oil, which were taken to represent human fat, corresponding values were about 450, 1300, and 3900. The coefficient for vinyl chloride in lard and olive oil was 20; the value in blood was too low to be determined by the technique used. Trichloroethylene, used as a marker, was found to have a coefficient in lard of 660, and in olive oil of 710, rather lower values than have been accepted for fat.", "contents": "Ostwald solubility coefficients of some industrially important substances. Solubility coefficients in blood for benzene, toluene, and xylene were determined as 6.5, 16, and 42 respectively. In lard and olive oil, which were taken to represent human fat, corresponding values were about 450, 1300, and 3900. The coefficient for vinyl chloride in lard and olive oil was 20; the value in blood was too low to be determined by the technique used. Trichloroethylene, used as a marker, was found to have a coefficient in lard of 660, and in olive oil of 710, rather lower values than have been accepted for fat."} {"id": "PMID:1276090", "title": "A proportional study of cancer registrations of dockyard workers.", "content": "Evidence of an occupational effect due to asbestos exposure was sought by comparing cancer registrations for dockyard workers with those for Plymouth men in the same age groups for 1960-69. The results show a significant excess of pleural tumours in the dockyard group but no significant excesses at other sites. Registrations for pleural mesothelioma were recorded for men with many dockyard occupations and the observed mean interval between first exposure to asbestos and registration for a pleural tumour (37.6 years) indicates that cases of pleural mesothelioma may be expected to occur among these workers for many years, even though crocidolite is no longer used in naval ships. A trend of increasing annual excess of stomach and gastrointestinal registrations was observed in the dockyard group. No cases of peritoneal mesothelioma were recorded but it is likely that some did occur which were diagnosed as cancers arising from other sites. This may account for some of the excess of gastrointestinal registrations.", "contents": "A proportional study of cancer registrations of dockyard workers. Evidence of an occupational effect due to asbestos exposure was sought by comparing cancer registrations for dockyard workers with those for Plymouth men in the same age groups for 1960-69. The results show a significant excess of pleural tumours in the dockyard group but no significant excesses at other sites. Registrations for pleural mesothelioma were recorded for men with many dockyard occupations and the observed mean interval between first exposure to asbestos and registration for a pleural tumour (37.6 years) indicates that cases of pleural mesothelioma may be expected to occur among these workers for many years, even though crocidolite is no longer used in naval ships. A trend of increasing annual excess of stomach and gastrointestinal registrations was observed in the dockyard group. No cases of peritoneal mesothelioma were recorded but it is likely that some did occur which were diagnosed as cancers arising from other sites. This may account for some of the excess of gastrointestinal registrations."} {"id": "PMID:1276091", "title": "Thirty-two cases of mesothelioma in Victoria, Australia: a retrospective survey related to occupational asbestos exposure.", "content": "Mesotheliomas have been reported in four states in Australia. Crocidolite has been mined and milled at Wittenoom in West Australia where five cases of mesothelioma were reported after exposure of high intensity. The 32 cases of mesothelioma reported in this paper occurred during a period of 11 years in Victoria; 29 were pleural and three peritoneal. There were 22 autopsies. End occupations were misleading in 66% of cases. Two of the three subjects with peritoneal mesothelioma were siblings, and there was no evidence of occupational or other exposure to asbestos in either. There was a significant prevalence of pulmonary asbestos bodies in the tumour series as compared with an unselected consecutive series of 200 routine autopsies (0.01 greater than P greater than 0.001). The occupational history was as effective a method of assessing 'true' asbestos exposure as the pulmonary asbestos body count. Five cases had had a duration of exposure of one year or less, but they had had heavy exposure. The latent interval before tumour development was 25 years or longer in each case. There was no known exposure to asbestos in five cases (16%). The rare association of mesothelioma with types of asbestos other than crocikolite may not exist and could be explicable on the basis of the proportion (16%) of these tumours arising randomly in the population.", "contents": "Thirty-two cases of mesothelioma in Victoria, Australia: a retrospective survey related to occupational asbestos exposure. Mesotheliomas have been reported in four states in Australia. Crocidolite has been mined and milled at Wittenoom in West Australia where five cases of mesothelioma were reported after exposure of high intensity. The 32 cases of mesothelioma reported in this paper occurred during a period of 11 years in Victoria; 29 were pleural and three peritoneal. There were 22 autopsies. End occupations were misleading in 66% of cases. Two of the three subjects with peritoneal mesothelioma were siblings, and there was no evidence of occupational or other exposure to asbestos in either. There was a significant prevalence of pulmonary asbestos bodies in the tumour series as compared with an unselected consecutive series of 200 routine autopsies (0.01 greater than P greater than 0.001). The occupational history was as effective a method of assessing 'true' asbestos exposure as the pulmonary asbestos body count. Five cases had had a duration of exposure of one year or less, but they had had heavy exposure. The latent interval before tumour development was 25 years or longer in each case. There was no known exposure to asbestos in five cases (16%). The rare association of mesothelioma with types of asbestos other than crocikolite may not exist and could be explicable on the basis of the proportion (16%) of these tumours arising randomly in the population."} {"id": "PMID:1276094", "title": "The in vitro effect of zinc on the inhibition of human delta-aminolevulinic acid dehydratase by lead.", "content": "The antagonistic effect of zinc on inhibibition of human aminolevulinic acid dehydratase (ALAD) by lead was examined in vitro. The phenomenon was studied at pH 6.5-7.5 . Zinc and lead were added at concentrations ranging from physiological levels to levels far in excess of those expected in heavy industrial exposure. ALAD activity of normal blood assayed in the presence of zinc was unaffected by exogenous lead if the added zinc concentration was above 0.53 mmol/l blood, or double the normal endogenous level, and was of the order found in heavy industrial exposure to zinc. In this case, ALAD assay values were appreciably raised and might have fallen into the normal range in spite of a dangerous total blood lead of over 0.0048 mmol/l. When zinc was added in vitro to blood from a worker with a blood lead level of 0.0043 mmol/l the ALAD values obtained were also raised and did not reflect the dangerous level of lead in the patient.", "contents": "The in vitro effect of zinc on the inhibition of human delta-aminolevulinic acid dehydratase by lead. The antagonistic effect of zinc on inhibibition of human aminolevulinic acid dehydratase (ALAD) by lead was examined in vitro. The phenomenon was studied at pH 6.5-7.5 . Zinc and lead were added at concentrations ranging from physiological levels to levels far in excess of those expected in heavy industrial exposure. ALAD activity of normal blood assayed in the presence of zinc was unaffected by exogenous lead if the added zinc concentration was above 0.53 mmol/l blood, or double the normal endogenous level, and was of the order found in heavy industrial exposure to zinc. In this case, ALAD assay values were appreciably raised and might have fallen into the normal range in spite of a dangerous total blood lead of over 0.0048 mmol/l. When zinc was added in vitro to blood from a worker with a blood lead level of 0.0043 mmol/l the ALAD values obtained were also raised and did not reflect the dangerous level of lead in the patient."} {"id": "PMID:1276095", "title": "Different behaviour of inorganic and organic mercury in renal excretion with reference to effects of D-penicillamine.", "content": "Inorganic and organic mercury was measured in the red cells, plasma, and urine of five laboratory workers to examine the effect of D-penicillamine. The workers had had no particular exposure to mercurials. Before and during administration of D-penicillamine, inorganic mercury levels in plasma were significantly correlated with those in urine or 24-hour urinary outputs, but no significant correlation was found for organic mercury. Administration of D-penicillamine enhanced 24-hour urinary output to a much greater extent in organic than inorganic mercury. All the organic mercury levels in blood, red cells, and plasma were increased by D-penicillamine. This contrasted with the decrease of inorganic mercury levels in plasma.", "contents": "Different behaviour of inorganic and organic mercury in renal excretion with reference to effects of D-penicillamine. Inorganic and organic mercury was measured in the red cells, plasma, and urine of five laboratory workers to examine the effect of D-penicillamine. The workers had had no particular exposure to mercurials. Before and during administration of D-penicillamine, inorganic mercury levels in plasma were significantly correlated with those in urine or 24-hour urinary outputs, but no significant correlation was found for organic mercury. Administration of D-penicillamine enhanced 24-hour urinary output to a much greater extent in organic than inorganic mercury. All the organic mercury levels in blood, red cells, and plasma were increased by D-penicillamine. This contrasted with the decrease of inorganic mercury levels in plasma."} {"id": "PMID:1276096", "title": "Shoe-makers' polyneuropathy in Italy: the aetiological problem.", "content": "Since 1957, when the first cases of the so-called shoe-makers' toxic polyneuropathy were reported, nearly 400 cases have been described in the Italian literature. The substance that was considered to be responsible for the disease was triorthocresylphosphate (TOCP) contained in glues, artificial leathers, and some types of paints. However numerous chemical analyses of glues and leathers taken from factories where cases of the disease occurred have shown that in almost all instances little or no TOCP was present. In addition the disease manifests itself more frequently during winter and spring and this is not consistent with the absorption of the causative agent through the skin and/or gastrointestinal tract. In order to clarify the aetiology of the disease 122 workers in the shoe industry affected by toxic polymeuropathy during the period 1971-74 were studied. Workplaces where cases of polyneuropathy had occurred were visited and samples of glues and solvents were taken for chemical analysis. The polyneuropathy chiefly affects workers engaged in glueing and in the cleaning process, but it also affects those who do not have direct contact with glues or solvents. The disease is more common in women (68%) than in men (32%) and, in its more severe form begins with overwhelming prevalence during winter and early spring regardless of the job performed. No direct relationship has been found between the severity of the disease and the number of years of work in the shoe industry or of specific exposure (that is the number of years of work in the activity performed at the onset of the disease). The polyneuropathy is found almost exclusively among workers of the artisam type in small shoe factories, where standards of hygiene are low. Chemical analysis of glues and cleaning fluids collected from five different factories, where 20 cases of polyneuropathy occurred, showed the presence of paraffin hydrocarbons with a low boiling point (pentane, 2-methyl-pentane, 3-methyl-pentane, n-hexane, etc.) in concentrations of more than 80% by weight.", "contents": "Shoe-makers' polyneuropathy in Italy: the aetiological problem. Since 1957, when the first cases of the so-called shoe-makers' toxic polyneuropathy were reported, nearly 400 cases have been described in the Italian literature. The substance that was considered to be responsible for the disease was triorthocresylphosphate (TOCP) contained in glues, artificial leathers, and some types of paints. However numerous chemical analyses of glues and leathers taken from factories where cases of the disease occurred have shown that in almost all instances little or no TOCP was present. In addition the disease manifests itself more frequently during winter and spring and this is not consistent with the absorption of the causative agent through the skin and/or gastrointestinal tract. In order to clarify the aetiology of the disease 122 workers in the shoe industry affected by toxic polymeuropathy during the period 1971-74 were studied. Workplaces where cases of polyneuropathy had occurred were visited and samples of glues and solvents were taken for chemical analysis. The polyneuropathy chiefly affects workers engaged in glueing and in the cleaning process, but it also affects those who do not have direct contact with glues or solvents. The disease is more common in women (68%) than in men (32%) and, in its more severe form begins with overwhelming prevalence during winter and early spring regardless of the job performed. No direct relationship has been found between the severity of the disease and the number of years of work in the shoe industry or of specific exposure (that is the number of years of work in the activity performed at the onset of the disease). The polyneuropathy is found almost exclusively among workers of the artisam type in small shoe factories, where standards of hygiene are low. Chemical analysis of glues and cleaning fluids collected from five different factories, where 20 cases of polyneuropathy occurred, showed the presence of paraffin hydrocarbons with a low boiling point (pentane, 2-methyl-pentane, 3-methyl-pentane, n-hexane, etc.) in concentrations of more than 80% by weight."} {"id": "PMID:1276097", "title": "The ultrasonic measurement of fetal crown-rump length as a method of assessing gestational age.", "content": "The fetal crown-rump length (CRL) was measured by means of pulsed ultrasound, and the normal values between 47 and 101 days from the onset of the last menstrual period were determined from cross-sectional data in 253 patients. For any given CRL, the range was found to be within three days of the menstrual age with a maximum variation for a given occasion of three days. Detailed statistical analysis showed that the acceleration in the rate of change in the CRL was a constant and that the intrapatient variability, where measured, was low. A close correlation between the measurement and the date of ovulation was demonstrated in a further 40 patients.", "contents": "The ultrasonic measurement of fetal crown-rump length as a method of assessing gestational age. The fetal crown-rump length (CRL) was measured by means of pulsed ultrasound, and the normal values between 47 and 101 days from the onset of the last menstrual period were determined from cross-sectional data in 253 patients. For any given CRL, the range was found to be within three days of the menstrual age with a maximum variation for a given occasion of three days. Detailed statistical analysis showed that the acceleration in the rate of change in the CRL was a constant and that the intrapatient variability, where measured, was low. A close correlation between the measurement and the date of ovulation was demonstrated in a further 40 patients."} {"id": "PMID:1276098", "title": "Urinary oestriol measurement in the management of antepartum haemorrhage.", "content": "In 51 patients with antepartum haemorrhage, 24-hour urinary oestriol was measured continuously until delivery. A total of 765 24-hour urinary oestriol measurements was obtained and there were two stillbirths, one neonatal death and three cases of intrauterine growth retardation in this group of patients. It was felt that none of the fetal deaths would have been prevented by obstetrical treatment based on 24-hour urinary oestriol measurements and that these have little practical value in the management of patients with antepartum haemorrhage.", "contents": "Urinary oestriol measurement in the management of antepartum haemorrhage. In 51 patients with antepartum haemorrhage, 24-hour urinary oestriol was measured continuously until delivery. A total of 765 24-hour urinary oestriol measurements was obtained and there were two stillbirths, one neonatal death and three cases of intrauterine growth retardation in this group of patients. It was felt that none of the fetal deaths would have been prevented by obstetrical treatment based on 24-hour urinary oestriol measurements and that these have little practical value in the management of patients with antepartum haemorrhage."} {"id": "PMID:1276099", "title": "Plasma oestriol in normal pregnancy in an Asian population.", "content": "Serial plasma oestriol levels were measured by a radioimmunoassay in 49 normal pregnancies, Plasma oestriol rose from 43 ng/ml (149-1 nmol/l) at 22 weeks to 357 ng/ml (1237-91 nmol/l) at 40 weeks. The rise was gradual between 22 and 32 weeks and steep between 32 and 40 weeks. No significant relationship could be found between plasma oestriol and parity, maternal age, maternal height, maternal weight or fetal sex. However, a significant but low correlation was found between birth weight and plasma oestriol prior to labour and also oestriol increments from 30 weeks to delivery. The average day to day coefficient of variation of plasma oestriol in 11 patients was found to be 16-2 per cent.", "contents": "Plasma oestriol in normal pregnancy in an Asian population. Serial plasma oestriol levels were measured by a radioimmunoassay in 49 normal pregnancies, Plasma oestriol rose from 43 ng/ml (149-1 nmol/l) at 22 weeks to 357 ng/ml (1237-91 nmol/l) at 40 weeks. The rise was gradual between 22 and 32 weeks and steep between 32 and 40 weeks. No significant relationship could be found between plasma oestriol and parity, maternal age, maternal height, maternal weight or fetal sex. However, a significant but low correlation was found between birth weight and plasma oestriol prior to labour and also oestriol increments from 30 weeks to delivery. The average day to day coefficient of variation of plasma oestriol in 11 patients was found to be 16-2 per cent."} {"id": "PMID:1276100", "title": "Lung function tests in bronchial asthma during and after pregnancy.", "content": "Respiratory function tests (forced vital capacity and forced expiratory volume in one second) were performed serially in pregnancy, the puerperium, and at least six weeks post partum in 27 patients with a history of asthma and in 12 control subjects. Eleven asthmatic patients with spirometric evidence of respiratory obstruction in pregnancy on at least one occasion were considered to have active disease. This group had significantly impaired respiratory function tests when compared to controls. The remaining 16 asthmatic patients were considered to be in remission. No changes in respiratory function tests attributable to pregnancy could be demonstrated in the asthma or control groups. Patients with active asthma tended to have smaller babies than patients with asthma in remission or the control patients.", "contents": "Lung function tests in bronchial asthma during and after pregnancy. Respiratory function tests (forced vital capacity and forced expiratory volume in one second) were performed serially in pregnancy, the puerperium, and at least six weeks post partum in 27 patients with a history of asthma and in 12 control subjects. Eleven asthmatic patients with spirometric evidence of respiratory obstruction in pregnancy on at least one occasion were considered to have active disease. This group had significantly impaired respiratory function tests when compared to controls. The remaining 16 asthmatic patients were considered to be in remission. No changes in respiratory function tests attributable to pregnancy could be demonstrated in the asthma or control groups. Patients with active asthma tended to have smaller babies than patients with asthma in remission or the control patients."} {"id": "PMID:1276101", "title": "The response of lymphocytes to phytohaemagglutinin in women with pre-eclampsia.", "content": "The response of maternal lymphocytes to phytohaemagglutinin was determined during and after pregnancy in patients with severe pre-eclampsia and in controls. The patients with pre-eclampsia showed a greater degree of immunosuppression during pregnancy than the normotensive controls. This was apparent in the presence and absence of maternal serum. In pre-eclampsia there may be an abnormality affecting the T cell subpopulation of lymphocytes and also a decreased immunosuppressive effect of maternal serum.", "contents": "The response of lymphocytes to phytohaemagglutinin in women with pre-eclampsia. The response of maternal lymphocytes to phytohaemagglutinin was determined during and after pregnancy in patients with severe pre-eclampsia and in controls. The patients with pre-eclampsia showed a greater degree of immunosuppression during pregnancy than the normotensive controls. This was apparent in the presence and absence of maternal serum. In pre-eclampsia there may be an abnormality affecting the T cell subpopulation of lymphocytes and also a decreased immunosuppressive effect of maternal serum."} {"id": "PMID:1276102", "title": "The use of the amniotic fluid lecithin/sphingomyelin (L/S) ratio, creatinine concentration and nile blue sulphate tests, individually and in combination, in the assessment of fetal lung maturity.", "content": "The lecithin-sphingomyelin (LS) ratio is a good, but not absolute, test of fetal lung maturity. A total of 373 infants was delivered within 72 hours of amniotic fluid collection for assessment of the L/S ratio. Five of 43 infants (11-6 per cent) with an L/S ratio of 2-2 or less developed the respiratory distress syndrome (RDS), whereas only one of 320 infants (0-31 per cent) with a higher L/S ratio developed RDS. The risk of RDS could be further defined by using the creatinine concentration (critical value 19 mg/1) and the Nile blue sulphate test (critical value 4 per cent) in combination with the L/S ratio. All three tests were performed in 320 pregnancies and in each instance delivery took place within 72 hours. When all three test results were low, 3 of 5 infants (60 per cent) developed RDS, whereas when all three results were high, none of 175 infants developed RDS. When one or two results were low, 2 of 140 infants (1-4 per cent) developed RDS.", "contents": "The use of the amniotic fluid lecithin/sphingomyelin (L/S) ratio, creatinine concentration and nile blue sulphate tests, individually and in combination, in the assessment of fetal lung maturity. The lecithin-sphingomyelin (LS) ratio is a good, but not absolute, test of fetal lung maturity. A total of 373 infants was delivered within 72 hours of amniotic fluid collection for assessment of the L/S ratio. Five of 43 infants (11-6 per cent) with an L/S ratio of 2-2 or less developed the respiratory distress syndrome (RDS), whereas only one of 320 infants (0-31 per cent) with a higher L/S ratio developed RDS. The risk of RDS could be further defined by using the creatinine concentration (critical value 19 mg/1) and the Nile blue sulphate test (critical value 4 per cent) in combination with the L/S ratio. All three tests were performed in 320 pregnancies and in each instance delivery took place within 72 hours. When all three test results were low, 3 of 5 infants (60 per cent) developed RDS, whereas when all three results were high, none of 175 infants developed RDS. When one or two results were low, 2 of 140 infants (1-4 per cent) developed RDS."} {"id": "PMID:1276103", "title": "The lecithin/sphingomyelin (L/S) ratio in twin pregnancies.", "content": "The lecithin/sphingomyelin (L/S) ratio has been estimated in the amniotic fluid from 20 patients with a twin pregnancy. The values in each pair of amniotic fluids were closely related. If amniotic fluid from one sac only is available, it is suggested that a ratio of 2-5:1 is taken as the lower limit to predict the functional lung maturity of both twins.", "contents": "The lecithin/sphingomyelin (L/S) ratio in twin pregnancies. The lecithin/sphingomyelin (L/S) ratio has been estimated in the amniotic fluid from 20 patients with a twin pregnancy. The values in each pair of amniotic fluids were closely related. If amniotic fluid from one sac only is available, it is suggested that a ratio of 2-5:1 is taken as the lower limit to predict the functional lung maturity of both twins."} {"id": "PMID:1276104", "title": "The effect of membrane rupture on fetal heart rate in induced labour.", "content": "The influence of the state of the membranes on the fetal heart rate was studied in a group of twelve women whose membranes were electively ruptured for oxytocin induction of labour. The results have been compared with a group of eight women of similar gestation and parity whose membranes were kept intact. While membranes were ruptured, there was an increase in the frequency and amplitude of early decelerations thorughout labour. The significance and practical implications of the results are discussed.", "contents": "The effect of membrane rupture on fetal heart rate in induced labour. The influence of the state of the membranes on the fetal heart rate was studied in a group of twelve women whose membranes were electively ruptured for oxytocin induction of labour. The results have been compared with a group of eight women of similar gestation and parity whose membranes were kept intact. While membranes were ruptured, there was an increase in the frequency and amplitude of early decelerations thorughout labour. The significance and practical implications of the results are discussed."} {"id": "PMID:1276105", "title": "Changes in the oral glucose tolerance test during the puerperium.", "content": "Oral glucose tolerance tests were performed during late pregnancy, on the second and fifth days of the puerperium and finally six weeks after delivery in a group of 12 healthy women. The glucose response showed no significant change from the pregnancy values on the second and fifth days of the puerperium but each woman had returned to 'normal' by the sixth week post partum. In contrast, the insulin response had returned to the non-pregnant value by the second day of the puerperium.", "contents": "Changes in the oral glucose tolerance test during the puerperium. Oral glucose tolerance tests were performed during late pregnancy, on the second and fifth days of the puerperium and finally six weeks after delivery in a group of 12 healthy women. The glucose response showed no significant change from the pregnancy values on the second and fifth days of the puerperium but each woman had returned to 'normal' by the sixth week post partum. In contrast, the insulin response had returned to the non-pregnant value by the second day of the puerperium."} {"id": "PMID:1276106", "title": "Monoamine oxidase activity in the fetal lung and liver.", "content": "Monoamine oxidase (MAO) in lung and liver is important in the degradation of circulating 5-hydroxytryptamine. These sites of MAO activity have been investigated histochemically in the human fetus of 12 to 18 weeks gestation. Enzyme activity could be demonstrated in the liver by both tryptamine and adrenaline oxidation. In the lung, MAO activity was present only when adrenaline was used to substrate. It may be, therefore, that in the premature baby the capacity of MAO to metabolize 5-hydroxytryptamine is not fully developed, which could lead to deleterious effects on pulmonary function.", "contents": "Monoamine oxidase activity in the fetal lung and liver. Monoamine oxidase (MAO) in lung and liver is important in the degradation of circulating 5-hydroxytryptamine. These sites of MAO activity have been investigated histochemically in the human fetus of 12 to 18 weeks gestation. Enzyme activity could be demonstrated in the liver by both tryptamine and adrenaline oxidation. In the lung, MAO activity was present only when adrenaline was used to substrate. It may be, therefore, that in the premature baby the capacity of MAO to metabolize 5-hydroxytryptamine is not fully developed, which could lead to deleterious effects on pulmonary function."} {"id": "PMID:1276107", "title": "Scanning electron microscope appearances of normal human amnion and umbilical cord at term.", "content": "The surface morphology of normal term amnion was studied by scanning electron microscopy. Four patterns were observed. Two of the patterns showed distinctive minority populations of cells. In one, there were cells surrounded by intracellular channels; in the other, there were large flat cells. The microvilli in all four patterns showed variable morphology in different samples. Possible functional implications of the findings are discussed.", "contents": "Scanning electron microscope appearances of normal human amnion and umbilical cord at term. The surface morphology of normal term amnion was studied by scanning electron microscopy. Four patterns were observed. Two of the patterns showed distinctive minority populations of cells. In one, there were cells surrounded by intracellular channels; in the other, there were large flat cells. The microvilli in all four patterns showed variable morphology in different samples. Possible functional implications of the findings are discussed."} {"id": "PMID:1276108", "title": "Intramuscular administration of 15-methyl-prostaglandin F(2alpha) for induction of labour in patients with intrauterine fetal death or an anencephalic fetus.", "content": "The 15-methyl analogue of PGF2alpha was administered intramuscularly between 23 and 36 weeks of gestation, to induce labour in 11 mothers with intrauterine fetal death and two with anencephaly. All were delivered within 20 hours (mean 7 hours). The mean dose of 15-me-PGF2alpha was 400 mug (range 100 to 700) given by a mean of 3-1 (range 1 to 7) injections. Diarrhoea was the most frequent side-effect.", "contents": "Intramuscular administration of 15-methyl-prostaglandin F(2alpha) for induction of labour in patients with intrauterine fetal death or an anencephalic fetus. The 15-methyl analogue of PGF2alpha was administered intramuscularly between 23 and 36 weeks of gestation, to induce labour in 11 mothers with intrauterine fetal death and two with anencephaly. All were delivered within 20 hours (mean 7 hours). The mean dose of 15-me-PGF2alpha was 400 mug (range 100 to 700) given by a mean of 3-1 (range 1 to 7) injections. Diarrhoea was the most frequent side-effect."} {"id": "PMID:1276109", "title": "Avulsion injury of uterovaginal prolapse and bladder.", "content": "A 40-year-old postmenopausal female with complete uterine prolapse received an avulsion injury when her sari was caught in the fast-moving belt of a flour mill machine. Part of the prolapsed anterior vaginal wall with underlying bladder wall was torn off. Primary repair together with vaginal hysterectomy led to an uneventful recovery.", "contents": "Avulsion injury of uterovaginal prolapse and bladder. A 40-year-old postmenopausal female with complete uterine prolapse received an avulsion injury when her sari was caught in the fast-moving belt of a flour mill machine. Part of the prolapsed anterior vaginal wall with underlying bladder wall was torn off. Primary repair together with vaginal hysterectomy led to an uneventful recovery."} {"id": "PMID:1276111", "title": "Effects of fast neutrons on the eye.", "content": "The study of 93 eyes receiving neutron irradiation establishes the character of the ophthalmic complications of neutron. Significant changes are produced in the eyelids, conjunctiva, and cornea, but the production of cataract is relatively unimportant. No reaction was seen after neutron treatment that had not already been seen after chi or gamma radiation. That the unavoidable damage is similar to that reported with other forms of radiation, and not worse, is an important finding in view of the statistically significant benefit of neutron treatment to patients in a controlled clinical trial of advanced tumours of the head and neck (Catterall and others, 1975). The observations indicate that the improved cure rates with neutrons are not obtained at the expense of inflicting greater damage to normal structures. This investigation has also shown that the neutron effects of treating these very extensive tumours are acceptable and that, with carefully measured doses, they are predictable. The dose-response relationship in categories of clinical effect for a smaller series of patients, reported in Table 1 of our preliminary communication (Brown and other, 1976), is confirmed.", "contents": "Effects of fast neutrons on the eye. The study of 93 eyes receiving neutron irradiation establishes the character of the ophthalmic complications of neutron. Significant changes are produced in the eyelids, conjunctiva, and cornea, but the production of cataract is relatively unimportant. No reaction was seen after neutron treatment that had not already been seen after chi or gamma radiation. That the unavoidable damage is similar to that reported with other forms of radiation, and not worse, is an important finding in view of the statistically significant benefit of neutron treatment to patients in a controlled clinical trial of advanced tumours of the head and neck (Catterall and others, 1975). The observations indicate that the improved cure rates with neutrons are not obtained at the expense of inflicting greater damage to normal structures. This investigation has also shown that the neutron effects of treating these very extensive tumours are acceptable and that, with carefully measured doses, they are predictable. The dose-response relationship in categories of clinical effect for a smaller series of patients, reported in Table 1 of our preliminary communication (Brown and other, 1976), is confirmed."} {"id": "PMID:1276112", "title": "Severe endemic trachoma in Tunisia.", "content": "In two villages in southern Tunisia where trachoma was endemic 7 per cent and 14 per cent of adults respectively had visual acuity of 20/400 or less. In both villages active trachoma affected most children under the age of two, reached a peak in two- to five-year-olds, then declined to age 15. The chronic inflammatory disease in childhood appeared to produce irreversible scarring of the eyelids, and loss of vision occurred in adult life due to corneal scarring caused by inturned eye lashes and loss of tears (dry-eyed syndrome). Economic development in one village was associated with a decline in active, infectious disease. In the second village, whose traditional economy was unchanged, there was the same prevalence of active disease over a three-year period. Unless economic development or public health control programmes reduce the prevalence of severe and moderate trachoma children now affected will develop the same blinding lesions as their parents. With the increasing numbers of children who survive there will probably be a dramatic increase in the numbers of the blind from trachoma in 10 to 20 years. Since active inflammatory trachoma in childhood responds to tetracyclines, erythromycin, and sulphonamides the disease should be attacked in those undeveloped rural areas where it continues to lead to blindness.", "contents": "Severe endemic trachoma in Tunisia. In two villages in southern Tunisia where trachoma was endemic 7 per cent and 14 per cent of adults respectively had visual acuity of 20/400 or less. In both villages active trachoma affected most children under the age of two, reached a peak in two- to five-year-olds, then declined to age 15. The chronic inflammatory disease in childhood appeared to produce irreversible scarring of the eyelids, and loss of vision occurred in adult life due to corneal scarring caused by inturned eye lashes and loss of tears (dry-eyed syndrome). Economic development in one village was associated with a decline in active, infectious disease. In the second village, whose traditional economy was unchanged, there was the same prevalence of active disease over a three-year period. Unless economic development or public health control programmes reduce the prevalence of severe and moderate trachoma children now affected will develop the same blinding lesions as their parents. With the increasing numbers of children who survive there will probably be a dramatic increase in the numbers of the blind from trachoma in 10 to 20 years. Since active inflammatory trachoma in childhood responds to tetracyclines, erythromycin, and sulphonamides the disease should be attacked in those undeveloped rural areas where it continues to lead to blindness."} {"id": "PMID:1276113", "title": "Simple method of determining the axial length of the eye.", "content": "By photographing the corneal reflex in two positions of gaze and measuring the radius of curvature of the cornea it is possible to calculate the radius of rotation of the eye. The measurements obtained in this way showed a high correlation with refraction in a series of 80 eyes. The axial length obtained by this method was about 3 mm greater than that obtained by ultrasonographic or x-ray methods, and the reasons for the discrepancy are discussed.", "contents": "Simple method of determining the axial length of the eye. By photographing the corneal reflex in two positions of gaze and measuring the radius of curvature of the cornea it is possible to calculate the radius of rotation of the eye. The measurements obtained in this way showed a high correlation with refraction in a series of 80 eyes. The axial length obtained by this method was about 3 mm greater than that obtained by ultrasonographic or x-ray methods, and the reasons for the discrepancy are discussed."} {"id": "PMID:1276114", "title": "Early and late results of fascia lata transplantation in high myopia.", "content": "Transplantation of a strip of fascia lata to strengthen the posterior sclera in high progressive myopia was performed on 184 eyes of 108 patients with myopia ranging from 7 to 39 D. Three weeks after surgery visual acuity with correction had improved by 0-1 to 0-5 in 151 eyes (82 per cent) and refractive power had decreased by 1 to 8 D in 169 eyes (92 per cent). In 105 eyes (67 patients) that were followed-up for periods of from 1 to 9 years myopia increased in six by 0-5 to 3 D. In 29 patients who had an operation on only one eye and were then followed-up for periods of from 1 to 7 years the degree of myopia in the fellow eye increased by 1-5 to 6 D in 24 (83 per cent), and of the eyes that were operated on myopia increased by 0-5 to 3 D in only 5 (17 per cent).", "contents": "Early and late results of fascia lata transplantation in high myopia. Transplantation of a strip of fascia lata to strengthen the posterior sclera in high progressive myopia was performed on 184 eyes of 108 patients with myopia ranging from 7 to 39 D. Three weeks after surgery visual acuity with correction had improved by 0-1 to 0-5 in 151 eyes (82 per cent) and refractive power had decreased by 1 to 8 D in 169 eyes (92 per cent). In 105 eyes (67 patients) that were followed-up for periods of from 1 to 9 years myopia increased in six by 0-5 to 3 D. In 29 patients who had an operation on only one eye and were then followed-up for periods of from 1 to 7 years the degree of myopia in the fellow eye increased by 1-5 to 6 D in 24 (83 per cent), and of the eyes that were operated on myopia increased by 0-5 to 3 D in only 5 (17 per cent)."} {"id": "PMID:1276115", "title": "Visually evoked cortical potentials in the evaluation of homonymous and bitemporal visual field defects.", "content": "Visually evoked cortical potentials were studied in six patients with a homonymous and six with a bitemporal hemianopia by presenting a pattern-reversal stimulus separately to a temporal or nasal retinal area and by recording the responses from leads over the hemispheres. Homonymous visual field defects are characterized by a reduction of VECPs from the affected hemisphere. The disturbance of VECPs in bitemporal hemianopia is more serious, since the fibres from both retinal halves may be damaged by a chiasm tumour.", "contents": "Visually evoked cortical potentials in the evaluation of homonymous and bitemporal visual field defects. Visually evoked cortical potentials were studied in six patients with a homonymous and six with a bitemporal hemianopia by presenting a pattern-reversal stimulus separately to a temporal or nasal retinal area and by recording the responses from leads over the hemispheres. Homonymous visual field defects are characterized by a reduction of VECPs from the affected hemisphere. The disturbance of VECPs in bitemporal hemianopia is more serious, since the fibres from both retinal halves may be damaged by a chiasm tumour."} {"id": "PMID:1276117", "title": "Senile cataract extraction and diabetes.", "content": "A study of hospital discharge diagnoses from both national data and data from a local medical centre indicates that diabetes substantially increases the probability of cataract extraction at age 40-49, about doubles or triples the probability for age 50-69, and has little effect on risk at age 70 and over. Strengths and weaknesses of the data are discussed. Other reports, generally estimating a much stronger association between diabetes and probability of cataract extraction, at least at age 50 and above, are critically evaluated.", "contents": "Senile cataract extraction and diabetes. A study of hospital discharge diagnoses from both national data and data from a local medical centre indicates that diabetes substantially increases the probability of cataract extraction at age 40-49, about doubles or triples the probability for age 50-69, and has little effect on risk at age 70 and over. Strengths and weaknesses of the data are discussed. Other reports, generally estimating a much stronger association between diabetes and probability of cataract extraction, at least at age 50 and above, are critically evaluated."} {"id": "PMID:1276118", "title": "Pigmented lens striae.", "content": "The clinical features of pigmented lens striae were studied biomicroscopically in seven patients. The lenses of three of these, obtained by cataract surgery, were examined by electron microscopy to determine the structure of the striae. We concluded that the striae are not formed by remnants of tunica vasculosa lentis, as earlier workers believed, but consist of fine fibrils of zonular bundles entrapping pigment granules of uveal origin.", "contents": "Pigmented lens striae. The clinical features of pigmented lens striae were studied biomicroscopically in seven patients. The lenses of three of these, obtained by cataract surgery, were examined by electron microscopy to determine the structure of the striae. We concluded that the striae are not formed by remnants of tunica vasculosa lentis, as earlier workers believed, but consist of fine fibrils of zonular bundles entrapping pigment granules of uveal origin."} {"id": "PMID:1276120", "title": "Immunoglobulins in endogenous uveitis.", "content": "Examination of 300 patients suffering from endogenous uveitis revealed raised levels of IgG in 24 per cent, IgA in 17 per cent, and IgM in 10 per cent. A raised level of one or more immunoglobulins was found more frequently in anterior uveitis than in the posterior form (44 compared with 24 per cent), in bilateral cases (47 compared with 35 per cent), and in relation to certain general diseases. No differences were demonstrated within the individual types of uveitis (fibrinous, nodular, etc.), nor was there any difference in prognosis (recurrence rate, visual impairment). Immunoglobulin levels were raised most often in elderly patients.", "contents": "Immunoglobulins in endogenous uveitis. Examination of 300 patients suffering from endogenous uveitis revealed raised levels of IgG in 24 per cent, IgA in 17 per cent, and IgM in 10 per cent. A raised level of one or more immunoglobulins was found more frequently in anterior uveitis than in the posterior form (44 compared with 24 per cent), in bilateral cases (47 compared with 35 per cent), and in relation to certain general diseases. No differences were demonstrated within the individual types of uveitis (fibrinous, nodular, etc.), nor was there any difference in prognosis (recurrence rate, visual impairment). Immunoglobulin levels were raised most often in elderly patients."} {"id": "PMID:1276121", "title": "Immunoglobulins in tears of normal Indian people.", "content": "Immunoglobulin concentrations in tears from 50 healthy Indians aged from 14 to 50 years were measured by a standard immunodiffusion method. The levels of IgA were substantial; those of IgG were very low; and IgD and IgM were not present. The mean IgA level was 24-6 mg/100 ml.", "contents": "Immunoglobulins in tears of normal Indian people. Immunoglobulin concentrations in tears from 50 healthy Indians aged from 14 to 50 years were measured by a standard immunodiffusion method. The levels of IgA were substantial; those of IgG were very low; and IgD and IgM were not present. The mean IgA level was 24-6 mg/100 ml."} {"id": "PMID:1276122", "title": "Interactions between arginine-rich histones and deoxyribonucleic acids. I. Thermal denaturation.", "content": "Physical properties of histone-DNA complexes very often depend upon the method of complex formation. In an attempt to make the studies of histone-DNA interactions more relevant to biological systems, results from thermal denaturation of native chromatin were used as references for determining how closely a given histone-DNA complex approaches its native state in chromatin. In the case of arginine-rich histones H3 (III or f3) and H4 (IV or f2a1), four methods were used for making complexes with calf thymus DNA: (A) NaCl gradient dialysis with urea; (B) NaCl gradient dialysis without urea; (C) direct mixing in 2.5 x 10(-4) EDTA, pH 8.0; and (D) direct mixing in 0.01 M sodium phosphate, pH 7.0. It was observed that a complex made by direct mixing in phosphate (method D) is closer to the native than is one made by direct mixing in EDTA (method C) than the one made by gradient dialysis with urea (method A) or without urea (method B). Regardless of the method used for complex formation, no substantial differences were observed between complexes with histone H3 dimer with disulfide bond(s) and a reduced H3 without disulfide bond, implying that perhaps a dimer with or without disulfide bond is a natural fundamental subunit in our experimental conditions. When the method of direct mixing in EDTA is used, the melting properties of the complexes vary only slightly with any one of the following H3 histones: from calf thymus, H3 without disulfide bond, H3 dimer, and H3 oligomer with disulfide bonds, also, from duck erythrocyte, H3 monomer and dimer. The complexes formed between DNA and a mixture of H3 and H4 by method D have melting properties similar to those of native chromatin. Since an equimolar mixture of histone H3 and H4 in 0.01 M phosphate, pH 7.0, was shown to form a tetramer (D'Anna, J.A., and Isenberg, I. (1974), Biochem. Biophys. Res. Commun. 61, 343), our results suggest that, a tetramer of H3 and H4, likely to be (H3)2(H4)2, formed from one H3 dimer and one H4 dimer, can bind DNA in a manner similar to that in native chromatin.", "contents": "Interactions between arginine-rich histones and deoxyribonucleic acids. I. Thermal denaturation. Physical properties of histone-DNA complexes very often depend upon the method of complex formation. In an attempt to make the studies of histone-DNA interactions more relevant to biological systems, results from thermal denaturation of native chromatin were used as references for determining how closely a given histone-DNA complex approaches its native state in chromatin. In the case of arginine-rich histones H3 (III or f3) and H4 (IV or f2a1), four methods were used for making complexes with calf thymus DNA: (A) NaCl gradient dialysis with urea; (B) NaCl gradient dialysis without urea; (C) direct mixing in 2.5 x 10(-4) EDTA, pH 8.0; and (D) direct mixing in 0.01 M sodium phosphate, pH 7.0. It was observed that a complex made by direct mixing in phosphate (method D) is closer to the native than is one made by direct mixing in EDTA (method C) than the one made by gradient dialysis with urea (method A) or without urea (method B). Regardless of the method used for complex formation, no substantial differences were observed between complexes with histone H3 dimer with disulfide bond(s) and a reduced H3 without disulfide bond, implying that perhaps a dimer with or without disulfide bond is a natural fundamental subunit in our experimental conditions. When the method of direct mixing in EDTA is used, the melting properties of the complexes vary only slightly with any one of the following H3 histones: from calf thymus, H3 without disulfide bond, H3 dimer, and H3 oligomer with disulfide bonds, also, from duck erythrocyte, H3 monomer and dimer. The complexes formed between DNA and a mixture of H3 and H4 by method D have melting properties similar to those of native chromatin. Since an equimolar mixture of histone H3 and H4 in 0.01 M phosphate, pH 7.0, was shown to form a tetramer (D'Anna, J.A., and Isenberg, I. (1974), Biochem. Biophys. Res. Commun. 61, 343), our results suggest that, a tetramer of H3 and H4, likely to be (H3)2(H4)2, formed from one H3 dimer and one H4 dimer, can bind DNA in a manner similar to that in native chromatin."} {"id": "PMID:1276123", "title": "Modification of histone binding in calf thymus chromatin and in the chromatin-protamine complex by acetic anhydride.", "content": "A relationship between side-chain modification of histones and their displaceability from DNA has been investigated using calf thymus chromatin which was chemically acetylated with acetic anhydride. When the chromatin is treated with increasingly higher concentrations of the reagent, histones become acetylated to an increasingly greater extent, attaining the modification at 23-24 sites for histone I, 5-6 for IIb1, 9-10 for IIb2, 5-6 for III and 3-4 for IV. As the chromatin becomes more acetylated, NaCl concentrations required for histone removal are lowered. Saturation binding of protamine does not bring about either an increase in the number of acetylation sites of histones in chromatin or a decrease of the NaCl requirement for dissociation of the acetylated chromatins. A comparison of the present results with the extents of histone acetylation known to occur enzymatically in vivo indicates that the complete removal of somatic histones during transformation of chromatin in spermiogenesis cannot be explained on the basis of decreased binding of the histone to DNA by acetylation or by a combination of acetylation and protamine binding, suggesting that the displacement process may require some additional processes.", "contents": "Modification of histone binding in calf thymus chromatin and in the chromatin-protamine complex by acetic anhydride. A relationship between side-chain modification of histones and their displaceability from DNA has been investigated using calf thymus chromatin which was chemically acetylated with acetic anhydride. When the chromatin is treated with increasingly higher concentrations of the reagent, histones become acetylated to an increasingly greater extent, attaining the modification at 23-24 sites for histone I, 5-6 for IIb1, 9-10 for IIb2, 5-6 for III and 3-4 for IV. As the chromatin becomes more acetylated, NaCl concentrations required for histone removal are lowered. Saturation binding of protamine does not bring about either an increase in the number of acetylation sites of histones in chromatin or a decrease of the NaCl requirement for dissociation of the acetylated chromatins. A comparison of the present results with the extents of histone acetylation known to occur enzymatically in vivo indicates that the complete removal of somatic histones during transformation of chromatin in spermiogenesis cannot be explained on the basis of decreased binding of the histone to DNA by acetylation or by a combination of acetylation and protamine binding, suggesting that the displacement process may require some additional processes."} {"id": "PMID:1276124", "title": "Complete displacement of somatic histones during transformation of spermatid chromatin: a model experiment.", "content": "Displacement of histones from calf thymus chromatin has been studied in an attempt to postulate the mechanisms involved in the total removal of somatic-type histones during transformation of spermatid chromatin. When chromatin is saturated with protamine (protamine/DNA, 0.5), histone I becomes displaceable at 0.15-0.3 M NaCl, suggesting that direct replacement by highly basic sperm histone could be a mechanism for its removal. While histone I is the only histone which is extensively degraded upon incubation of chromatin and, therefore, proteolysis might provide an additional mechanism for the removal of this histone, acetylation of chromatin by acetic anhydride greatly increases suscpetibility of histones IIb1, IIb2, and III to the chromosomally associated protease. These histones are extensively degraded and displaced from the DNA upon incubation of the acetylated chromatin. Although histone IV is not appreciably degraded, the proteolytic removal of acetylated histone III from chromatin weakens the interaction of acetylated histone IV to the DNA, and this histone becomes dissociable at 0.3 M NaCl. A comparison of the extent of chemical acetylation of individual histones observed in this investigation with that of enzymatic acetylation which can be achieved in vivo suggests that acetylation and proteolysis could be a mechanism for the removal of histone IIb2 and III. The displacement of histones IIb1 and IV could be explained on the basis of decreased binding to DNA as a result of their acetylation together with the proteolytic removal of their respective partner histones, IIb2 and III.", "contents": "Complete displacement of somatic histones during transformation of spermatid chromatin: a model experiment. Displacement of histones from calf thymus chromatin has been studied in an attempt to postulate the mechanisms involved in the total removal of somatic-type histones during transformation of spermatid chromatin. When chromatin is saturated with protamine (protamine/DNA, 0.5), histone I becomes displaceable at 0.15-0.3 M NaCl, suggesting that direct replacement by highly basic sperm histone could be a mechanism for its removal. While histone I is the only histone which is extensively degraded upon incubation of chromatin and, therefore, proteolysis might provide an additional mechanism for the removal of this histone, acetylation of chromatin by acetic anhydride greatly increases suscpetibility of histones IIb1, IIb2, and III to the chromosomally associated protease. These histones are extensively degraded and displaced from the DNA upon incubation of the acetylated chromatin. Although histone IV is not appreciably degraded, the proteolytic removal of acetylated histone III from chromatin weakens the interaction of acetylated histone IV to the DNA, and this histone becomes dissociable at 0.3 M NaCl. A comparison of the extent of chemical acetylation of individual histones observed in this investigation with that of enzymatic acetylation which can be achieved in vivo suggests that acetylation and proteolysis could be a mechanism for the removal of histone IIb2 and III. The displacement of histones IIb1 and IV could be explained on the basis of decreased binding to DNA as a result of their acetylation together with the proteolytic removal of their respective partner histones, IIb2 and III."} {"id": "PMID:1276125", "title": "Secondary structure of ovalbumin messenger RNA.", "content": "The secondary structure of highly purified ovalbumin mRNA was studied by automated thermal denaturation techniques and the data were subjected to computer processing. Comparative studies with 20 natural and synthetic model nucleic acids suggested that the secondary structure of ovalbumin mRNA possesses the following features: the extent of base pairing of ovalbumin mRNA is similar to that found in tRNAs or ribosomal RNAs; the secondary structure of ovalbumin mRNA is more thermolabile than any of the model compounds tested, including the copolymer poly(A-U); ovalbumin mRNA does not have extensive G-C rich stems as found in tRNAs or ribosomal RNAs; the base composition of the double-stranded regions reveals 54% G-C residues which was significantly higher than that noted in the whole molecule (approximately 41.5% G-C). The presence of 46% A-U pairs in short stems of about five base pairs would have a very large destabilizing effect on the secondary structure of ovalbumin mRNA. However, at 0.175 M monovalent cations and 36 degrees C most of the secondary structure of ovalbumin mRNA is preserved. These data suggest that the double-stranded regions in ovalbumin mRNA are of sufficient length to provide the necessary stability for maintaining the open loop regions in an appropriate conformation which may be required for the biological function of ovalbumin mRNA. Furthermore, the lability of the double-stranded regions in ovalbumin mRNA may also be important for the biological function of this mRNA.", "contents": "Secondary structure of ovalbumin messenger RNA. The secondary structure of highly purified ovalbumin mRNA was studied by automated thermal denaturation techniques and the data were subjected to computer processing. Comparative studies with 20 natural and synthetic model nucleic acids suggested that the secondary structure of ovalbumin mRNA possesses the following features: the extent of base pairing of ovalbumin mRNA is similar to that found in tRNAs or ribosomal RNAs; the secondary structure of ovalbumin mRNA is more thermolabile than any of the model compounds tested, including the copolymer poly(A-U); ovalbumin mRNA does not have extensive G-C rich stems as found in tRNAs or ribosomal RNAs; the base composition of the double-stranded regions reveals 54% G-C residues which was significantly higher than that noted in the whole molecule (approximately 41.5% G-C). The presence of 46% A-U pairs in short stems of about five base pairs would have a very large destabilizing effect on the secondary structure of ovalbumin mRNA. However, at 0.175 M monovalent cations and 36 degrees C most of the secondary structure of ovalbumin mRNA is preserved. These data suggest that the double-stranded regions in ovalbumin mRNA are of sufficient length to provide the necessary stability for maintaining the open loop regions in an appropriate conformation which may be required for the biological function of ovalbumin mRNA. Furthermore, the lability of the double-stranded regions in ovalbumin mRNA may also be important for the biological function of this mRNA."} {"id": "PMID:1276126", "title": "Statistical interpretation of fluorescence energy transfer measurements in macromolecular systems.", "content": "A statistical method is presented for the interpretation of intramolecular distance measurements by the fluorescence energy transfer technique in systems for which the detailed geometries of the donor-acceptor pairs are unknown. This method enables calculation of the probability that a specified distance range corresponds to the actual distance to be measured. It makes use of the numerically calculated probability density function for the distance of interest. The two general systems considered are the single donor-acceptor pair and the multi-donor-single-acceptor transfer. In both systems, the statistical method incorporates the uncertainty in the orientation of the donor and acceptor dipoles. In addition, it can take into account the rotational mobility of the donor dipoles determined by time-dependent emission anisotropy measurements. When more than one donor is involved in the transfer process, the uncertainties associated with the number and location of individual donors and the size and shape of the donor distribution are also incorporated in calculating the distance ranges. Application of the method was demonstrated for a wide range of transfer efficiency and Ro values for the single donor-acceptor system. Specific examples are also presented for interpretation of both single donor-acceptor and multi-donor-single-acceptor energy transfer measurements performed in order to reveal the spatial relationship of the sigma subunit and the rifampicin binding site in the Escherichia coli RNA polymerase (see Wu, C.-W., Yarbrough, L. R., Wu, F. Y.-H., and Hillel, Z. (1976), Biochemistry, preceding paper in this issue). Analysis of these energy transfer data by methods which use average values of the unknown geometrical parameters of the system yielded results similar to those obtained by the statistical method. However, the statistical method represents a more realistic approach to the interpretation of energy transfer measurements since it provides information concerning the entire range of possible distances and their relative likelihood.", "contents": "Statistical interpretation of fluorescence energy transfer measurements in macromolecular systems. A statistical method is presented for the interpretation of intramolecular distance measurements by the fluorescence energy transfer technique in systems for which the detailed geometries of the donor-acceptor pairs are unknown. This method enables calculation of the probability that a specified distance range corresponds to the actual distance to be measured. It makes use of the numerically calculated probability density function for the distance of interest. The two general systems considered are the single donor-acceptor pair and the multi-donor-single-acceptor transfer. In both systems, the statistical method incorporates the uncertainty in the orientation of the donor and acceptor dipoles. In addition, it can take into account the rotational mobility of the donor dipoles determined by time-dependent emission anisotropy measurements. When more than one donor is involved in the transfer process, the uncertainties associated with the number and location of individual donors and the size and shape of the donor distribution are also incorporated in calculating the distance ranges. Application of the method was demonstrated for a wide range of transfer efficiency and Ro values for the single donor-acceptor system. Specific examples are also presented for interpretation of both single donor-acceptor and multi-donor-single-acceptor energy transfer measurements performed in order to reveal the spatial relationship of the sigma subunit and the rifampicin binding site in the Escherichia coli RNA polymerase (see Wu, C.-W., Yarbrough, L. R., Wu, F. Y.-H., and Hillel, Z. (1976), Biochemistry, preceding paper in this issue). Analysis of these energy transfer data by methods which use average values of the unknown geometrical parameters of the system yielded results similar to those obtained by the statistical method. However, the statistical method represents a more realistic approach to the interpretation of energy transfer measurements since it provides information concerning the entire range of possible distances and their relative likelihood."} {"id": "PMID:1276127", "title": "Structure in the polar head region of phospholipid bilayers: A 31P [1H] nuclear Overhauser effect study.", "content": "The structure of the head-group region of some phospholipid bilayers in vesicle form has been studied and an intermolecular association of the N-methyl protons of phosphatidylcholine (PC) with the phosphate of phosphatidylethanolamine (PE) in mixed vesicles has been identified. Observation of a 31P[1H] nuclear Overhauser effect (NOE) in the phosphorus nuclear magnetic resonances of both PC and PE in mixed vesicles demonstrates an intimate dipolar interaction between some protons and the phosphorus nuclei. Substitution of deuterium for the N-methyl protons of PC eliminated the majority of the effect and necessitated the construction of a model of the bilayer surface in which the N-methyl protons of PC could interact closely with the phosphates of neighboring PE molecules. The predominant orientation of the head group must then be parallel to the bilayer surface. The amino protons of PE do not contribute significantly to the observed NOE. A corollary of these results is that there is little if any tendency for either PC or PE in the mixed vesicles to segregate into separate domains. A decrease in NOE in sphingomyelin vesicles on going from H2O to D2O suggests that an exchangeable proton contributes to the NOE. In addition the low value of the NOE observed in D2O suggests that the head-group conformation of sphingomyelin differs from that of PC.", "contents": "Structure in the polar head region of phospholipid bilayers: A 31P [1H] nuclear Overhauser effect study. The structure of the head-group region of some phospholipid bilayers in vesicle form has been studied and an intermolecular association of the N-methyl protons of phosphatidylcholine (PC) with the phosphate of phosphatidylethanolamine (PE) in mixed vesicles has been identified. Observation of a 31P[1H] nuclear Overhauser effect (NOE) in the phosphorus nuclear magnetic resonances of both PC and PE in mixed vesicles demonstrates an intimate dipolar interaction between some protons and the phosphorus nuclei. Substitution of deuterium for the N-methyl protons of PC eliminated the majority of the effect and necessitated the construction of a model of the bilayer surface in which the N-methyl protons of PC could interact closely with the phosphates of neighboring PE molecules. The predominant orientation of the head group must then be parallel to the bilayer surface. The amino protons of PE do not contribute significantly to the observed NOE. A corollary of these results is that there is little if any tendency for either PC or PE in the mixed vesicles to segregate into separate domains. A decrease in NOE in sphingomyelin vesicles on going from H2O to D2O suggests that an exchangeable proton contributes to the NOE. In addition the low value of the NOE observed in D2O suggests that the head-group conformation of sphingomyelin differs from that of PC."} {"id": "PMID:1276128", "title": "C55-Dolichol: occurrence in pig liver and preparation by hydrogenation of plant undecaprenol.", "content": "Apart from the long-chain dolichols (C80-C110), pig liver contains also a family of much shorter polyprenols with dominating C55-polyprenol. This compound was identified as cis/trans-dihydroundecaprenol in which the OH-terminal isoprene residue was saturated. The number of internal trans isoprene residues in this compound was three in comparison with two such residues in long-chain C95-dolichol. Chemical preparation of dihydroundecaprenol with a selectively saturated OH-terminal isoprene residue from fully unsaturated plant undecaprenol is presented.", "contents": "C55-Dolichol: occurrence in pig liver and preparation by hydrogenation of plant undecaprenol. Apart from the long-chain dolichols (C80-C110), pig liver contains also a family of much shorter polyprenols with dominating C55-polyprenol. This compound was identified as cis/trans-dihydroundecaprenol in which the OH-terminal isoprene residue was saturated. The number of internal trans isoprene residues in this compound was three in comparison with two such residues in long-chain C95-dolichol. Chemical preparation of dihydroundecaprenol with a selectively saturated OH-terminal isoprene residue from fully unsaturated plant undecaprenol is presented."} {"id": "PMID:1276129", "title": "Isolation of an inhibitor of 25-hydroxyvitamin D3-1-hydroxylase from rat serum.", "content": "An inhibitor of chick kidney mitochondrial 25-hydroxyvitamin D3-1-hydroxylase has been isolated from rat serum by ammonium sulfate precipitation, gel filtration, ionexchange chromatography, and preparative polyacrylamide disc gel electrophoresis. The purified protein was shown to contain iron and has a mol wt of 52 000. The protein is indistinguishable on gel electrophoresis from a similar inhibitor found in rat kidney tissue. The physiological significance of the inhibitor is not known; however, it seems possible that it is responsible for the failure to demonstrate in vitro 25-hydroxyvitamin D3-l-hydroxylation with rat and other mammalian tissues.", "contents": "Isolation of an inhibitor of 25-hydroxyvitamin D3-1-hydroxylase from rat serum. An inhibitor of chick kidney mitochondrial 25-hydroxyvitamin D3-1-hydroxylase has been isolated from rat serum by ammonium sulfate precipitation, gel filtration, ionexchange chromatography, and preparative polyacrylamide disc gel electrophoresis. The purified protein was shown to contain iron and has a mol wt of 52 000. The protein is indistinguishable on gel electrophoresis from a similar inhibitor found in rat kidney tissue. The physiological significance of the inhibitor is not known; however, it seems possible that it is responsible for the failure to demonstrate in vitro 25-hydroxyvitamin D3-l-hydroxylation with rat and other mammalian tissues."} {"id": "PMID:1276130", "title": "A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Purification from porcine muscle.", "content": "Ca2+-activated Z-disk-removing activity in the P0-40 crude muscle extracts described by Busch et al. (Busch, W. A., Stromer, M. H., Goll, D. E., and Suzuki, A. (1972), J. Cell Biol. 52, 367) was purified from porcine skeletal muscle extracts by using five column chromatographic procedures in succession: (1) 6% agarose; (2) DEAE-cellulose; (3) Sephadex G-200; (4) DEAE-cellulose with a very shallow gradient; (5) Sephadex G-150. All Z-disk-removing activity eluted in a single peak off each column. Z-disk-removing activity always coeluted with Ca2+-activated proteolytic activity, so Z-disk-removing activity in the P0-40 crude muscle extract is due to a single Ca2+-activated protease (CAF). The five column chromatographic procedures produced a 140-fold increase in specific activity of the Ca2+-activated proteolytic enzymic activity; because preparation of the P0-40 crude CAF fraction before chromatography produced a 127-fold increase in specific activity, the entire procedure described here produces a 17 800-fold increase in specific activity of CAF. This increase in specific activity suggests that muscle contains 3.4 mug of CAF per g of muscle fresh weight; this content is in reasonably good agreement with our yields of 0.25-0.76 mug of purified CAF per g of muscle. Purified CAF migrated as a single band during polyacrylamide gel electrophoresis in pH 7.5 Tris-HC1 buffer but migrated as two bands with molecular weights of 80 000 and 30 000 during polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Densitometric scans of sodium dodecyl sulfate-polyacrylamide gels show that the 80 000- and 30 000-dalton subunits make up 85 to 90% of the protein in purified CAF preparations and that these subunits are present in equimolar ratios.", "contents": "A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Purification from porcine muscle. Ca2+-activated Z-disk-removing activity in the P0-40 crude muscle extracts described by Busch et al. (Busch, W. A., Stromer, M. H., Goll, D. E., and Suzuki, A. (1972), J. Cell Biol. 52, 367) was purified from porcine skeletal muscle extracts by using five column chromatographic procedures in succession: (1) 6% agarose; (2) DEAE-cellulose; (3) Sephadex G-200; (4) DEAE-cellulose with a very shallow gradient; (5) Sephadex G-150. All Z-disk-removing activity eluted in a single peak off each column. Z-disk-removing activity always coeluted with Ca2+-activated proteolytic activity, so Z-disk-removing activity in the P0-40 crude muscle extract is due to a single Ca2+-activated protease (CAF). The five column chromatographic procedures produced a 140-fold increase in specific activity of the Ca2+-activated proteolytic enzymic activity; because preparation of the P0-40 crude CAF fraction before chromatography produced a 127-fold increase in specific activity, the entire procedure described here produces a 17 800-fold increase in specific activity of CAF. This increase in specific activity suggests that muscle contains 3.4 mug of CAF per g of muscle fresh weight; this content is in reasonably good agreement with our yields of 0.25-0.76 mug of purified CAF per g of muscle. Purified CAF migrated as a single band during polyacrylamide gel electrophoresis in pH 7.5 Tris-HC1 buffer but migrated as two bands with molecular weights of 80 000 and 30 000 during polyacrylamide gel electrophoresis in sodium dodecyl sulfate. Densitometric scans of sodium dodecyl sulfate-polyacrylamide gels show that the 80 000- and 30 000-dalton subunits make up 85 to 90% of the protein in purified CAF preparations and that these subunits are present in equimolar ratios."} {"id": "PMID:1276131", "title": "A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Partial characterization of the purified enzyme.", "content": "The purified Ca2+-activated protease (CAF) isolated from porcine skeletal muscle and capable of removing Z-disks from intact myofibrils is optimally active on either myofibril or casein substrates at pH 7.5 and in the presence of 1 mM Ca2+ and at least 2 mM 2-mercaptoethanol. No CAF activity is detected when 1 mM Mg2+, Mn2+, Ba2+, Co2+, Ni2+, and Fe2+ are added singly. When added with 1 mM Ca2+, Co2+, Cu2+, Ni2+, and Fe2+ inhibit, whereas Mg2+, Mn2+, and Ba2+ have no effect on CAF activity. CAF is irreversibly inhibited by iodoacetate but is unaffected by soybean trypsin inhibitor. S0/20,W=5.90 S, and sedimentation equilibrium molecular weight - 112 000 for purified CAF. Because purified CAF migrates as two polypeptide chains with molecular weights of 80 000 and 30 000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the CAF molecule must consist of one each of these two polypeptide chains. Approximate molecular dimensions of 38 X 220 A can be calculated for CAF from calibrated gel permeation column data or from S0/20,W and the molecular weight. Amino acid composition and physical properties of purified CAF distinguish it from the known catheptic enzymes and from other proteases found in blood or in granulocytes. Purified CAF removes Z-disks the 400-A periodicity associated with troponin in the I band and partly degrades M lines but causes no other ultrastructurally detectable effects when incubated with myofibrils. These results agree with the earlier finding that purified CAF degrades troponin, tropomyosin, and C-protein but has no effect on myosin, actin, or alpha-actinin, and suggest that CAF may have a physiological role in disassembly of intact myofibrils during metabolic turnover of myofibrillar proteins.", "contents": "A Ca2+-activated protease possibly involved in myofibrillar protein turnover. Partial characterization of the purified enzyme. The purified Ca2+-activated protease (CAF) isolated from porcine skeletal muscle and capable of removing Z-disks from intact myofibrils is optimally active on either myofibril or casein substrates at pH 7.5 and in the presence of 1 mM Ca2+ and at least 2 mM 2-mercaptoethanol. No CAF activity is detected when 1 mM Mg2+, Mn2+, Ba2+, Co2+, Ni2+, and Fe2+ are added singly. When added with 1 mM Ca2+, Co2+, Cu2+, Ni2+, and Fe2+ inhibit, whereas Mg2+, Mn2+, and Ba2+ have no effect on CAF activity. CAF is irreversibly inhibited by iodoacetate but is unaffected by soybean trypsin inhibitor. S0/20,W=5.90 S, and sedimentation equilibrium molecular weight - 112 000 for purified CAF. Because purified CAF migrates as two polypeptide chains with molecular weights of 80 000 and 30 000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the CAF molecule must consist of one each of these two polypeptide chains. Approximate molecular dimensions of 38 X 220 A can be calculated for CAF from calibrated gel permeation column data or from S0/20,W and the molecular weight. Amino acid composition and physical properties of purified CAF distinguish it from the known catheptic enzymes and from other proteases found in blood or in granulocytes. Purified CAF removes Z-disks the 400-A periodicity associated with troponin in the I band and partly degrades M lines but causes no other ultrastructurally detectable effects when incubated with myofibrils. These results agree with the earlier finding that purified CAF degrades troponin, tropomyosin, and C-protein but has no effect on myosin, actin, or alpha-actinin, and suggest that CAF may have a physiological role in disassembly of intact myofibrils during metabolic turnover of myofibrillar proteins."} {"id": "PMID:1276132", "title": "Kinetics of the action of papain on fluorescent peptide substrates.", "content": "Kinetic measurements have been performed on the action of papain on mansyl-Gly-Val-Glu-Leu-Gly and on mansyl-Gly-Gly-Val-Glu-Leu-Gly, both of which are cleaved solely at the Glu-Leu bond under the conditions of our experiments. Stopped-flow experiments have shown that, under conditions of enzyme excess, the enhancement of the fluorescence of the mansyl group upon association of each of the oligopeptide substrates with papain is a biphasic process. A very rapid initial increase in fluorescence is followed by a slower first-order fluorescence enhancement. The observed rate constant for the latter process is greater with the mansyl pentapeptide than with the mansyl hexapeptide. A similar biphasic fluorescence change is seen upon the interaction of the mansyl peptides with mercuripapain, but the second step is much slower than in the case of the active enzyme. The rate of the second step in the association of active papain with the mansyl paptides shows saturation with increasing enzyme concentration, supporting the view that an initial enzyme-substrate complex (ES) is converted in a first-order process to the complex (ES) that undergoes cleavage to form products. The hydrolysis of the Glu-Leu bond is associated with a first-order decrease in fluorescence, as a consequence of the formation of the mansyl peptide product, which is bound less strongly than the substrate. The rate constant for this process is about 140 times greater with the mansyl hexapeptide than with the mansyl pentapeptide, thus giving further indication of the importance of secondary enzyme-substrate interactions in the efficiency of papain catalysis. For each of the two mansyl peptides, the values of the rate constants and the apparent Michaelis constants associated with the cleavage of the Glu-Leu bond, as determined by stopped-flow measurements under conditions of enzyme excess, were the same, within the precision of the data, as those estimated from experiments under conditions of substrate excess, where the formation of Leu-Gly was determined by means of the fluorescamine reaction. This indicates that, with these substrates, the rate-limiting step in the overall catalytic process is associated with the breakdown of ES. Estimates are given of the dissociation constant of ES and of the rate constants in the interconversion of ES and ES.", "contents": "Kinetics of the action of papain on fluorescent peptide substrates. Kinetic measurements have been performed on the action of papain on mansyl-Gly-Val-Glu-Leu-Gly and on mansyl-Gly-Gly-Val-Glu-Leu-Gly, both of which are cleaved solely at the Glu-Leu bond under the conditions of our experiments. Stopped-flow experiments have shown that, under conditions of enzyme excess, the enhancement of the fluorescence of the mansyl group upon association of each of the oligopeptide substrates with papain is a biphasic process. A very rapid initial increase in fluorescence is followed by a slower first-order fluorescence enhancement. The observed rate constant for the latter process is greater with the mansyl pentapeptide than with the mansyl hexapeptide. A similar biphasic fluorescence change is seen upon the interaction of the mansyl peptides with mercuripapain, but the second step is much slower than in the case of the active enzyme. The rate of the second step in the association of active papain with the mansyl paptides shows saturation with increasing enzyme concentration, supporting the view that an initial enzyme-substrate complex (ES) is converted in a first-order process to the complex (ES) that undergoes cleavage to form products. The hydrolysis of the Glu-Leu bond is associated with a first-order decrease in fluorescence, as a consequence of the formation of the mansyl peptide product, which is bound less strongly than the substrate. The rate constant for this process is about 140 times greater with the mansyl hexapeptide than with the mansyl pentapeptide, thus giving further indication of the importance of secondary enzyme-substrate interactions in the efficiency of papain catalysis. For each of the two mansyl peptides, the values of the rate constants and the apparent Michaelis constants associated with the cleavage of the Glu-Leu bond, as determined by stopped-flow measurements under conditions of enzyme excess, were the same, within the precision of the data, as those estimated from experiments under conditions of substrate excess, where the formation of Leu-Gly was determined by means of the fluorescamine reaction. This indicates that, with these substrates, the rate-limiting step in the overall catalytic process is associated with the breakdown of ES. Estimates are given of the dissociation constant of ES and of the rate constants in the interconversion of ES and ES."} {"id": "PMID:1276133", "title": "Carbamoylated hemoglobins A and S: physical properties.", "content": "Dimer-tetramer association constants (K2,4) of derivatives of CO-hemoglobins A and S specifically carbamoylated at the NH2-terminal valine residues were measured. Reactivites of the beta-93 sulfhydryls of the hemoglobin A derivatives were also investigated. As compared with the association constants of the parent molecules, the values of K2,4 of both hemoglobin types are raised by carbamoylation of the alpha-chain NH2 terminus, lowered by carbamoylation of the beta-chain NH2 terminus, and raised by carbamoylation of both termini. The apparent second-order rate constant for reaction of p-mercuribenzoate (PMB) with the beta-93 sulfhydryls is, however, unchanged by carbamoylation. These two observations are interpreted to indicate that in the liganded molecule structural changes are produced at the interface between dimers but not in the region of the beta-93 sulfhydryls. From the combination of the K2,4 measurements with ligand-binding data for the same derivatives (Kilmartin, J. V., et al. (1973), J. Biol. Chem. 248, 4039; Nigen, A. M., et al. (1974), J. Biol. Chem. 249, 6611) the carbamoylation-induced changes in the dimer-tetramer association constants of the unliganded derivatives were estimated to be of magnitude equal to or smaller than those in K2,4. It is concluded that much of the change in oxygen affinity that occurs upon carbamoylation of hemoglobins A and S can be accounted for without invoking extensive structural changes in the unliganded molecule.", "contents": "Carbamoylated hemoglobins A and S: physical properties. Dimer-tetramer association constants (K2,4) of derivatives of CO-hemoglobins A and S specifically carbamoylated at the NH2-terminal valine residues were measured. Reactivites of the beta-93 sulfhydryls of the hemoglobin A derivatives were also investigated. As compared with the association constants of the parent molecules, the values of K2,4 of both hemoglobin types are raised by carbamoylation of the alpha-chain NH2 terminus, lowered by carbamoylation of the beta-chain NH2 terminus, and raised by carbamoylation of both termini. The apparent second-order rate constant for reaction of p-mercuribenzoate (PMB) with the beta-93 sulfhydryls is, however, unchanged by carbamoylation. These two observations are interpreted to indicate that in the liganded molecule structural changes are produced at the interface between dimers but not in the region of the beta-93 sulfhydryls. From the combination of the K2,4 measurements with ligand-binding data for the same derivatives (Kilmartin, J. V., et al. (1973), J. Biol. Chem. 248, 4039; Nigen, A. M., et al. (1974), J. Biol. Chem. 249, 6611) the carbamoylation-induced changes in the dimer-tetramer association constants of the unliganded derivatives were estimated to be of magnitude equal to or smaller than those in K2,4. It is concluded that much of the change in oxygen affinity that occurs upon carbamoylation of hemoglobins A and S can be accounted for without invoking extensive structural changes in the unliganded molecule."} {"id": "PMID:1276134", "title": "Infrared spectroscopic studies of carbonyl horseradish peroxidases.", "content": "Infrared difference spectra, FeIIICO vs. FeIII of horseradish peroxidase isoenzymes A2 and C were recorded from 2000 to 1800 cm-1. Under alkaline conditions, pH 9, both isoenzymes exhibit two CO stretching bands, at 1938 and 1925 cm-1 for A2 and at 1933 and 1929 cm-1 for C. As the pH is lowered the low-frequency band for each isoenzyme decreases in intensity with a concommitant appearance and increase in intensity of a band at 1906 and 1905 cm-1 for the A2 and C isoenzymes, respectively. These changes conform to pK values of 6.7 for the A2 and 8.8 for the C isoenzymes of horseradish peroxidase. The interpretation of the infrared results was simplified by the observation that a linear relationship exists between the redox potential, Em7, for the FeIII/FeII system vs. the infrared CO stretching frequency, vCO, for cytochrome a3, hemoglobin, myoglobin, and cytochrome P-450 cam with substrate. This relationship suggests that the primary force altering vCO in these heme proteins is a variation in electron density at the heme iron and not direct protein interactions with the CO ligand. The horseradish peroxidase infrared bands in the 1930-cm-1 region correlate well with this relationship. The large deviation of the 1905-cm-1 band from the linear relationship and its dependence upon hydrogen ion concentration are consistent with horseradish peroxidase having a single CO binding site which can hold in two geometries, one of which contains an amino acid moiety capable of forming a hydrogen bond to the carbonyl oxygen.", "contents": "Infrared spectroscopic studies of carbonyl horseradish peroxidases. Infrared difference spectra, FeIIICO vs. FeIII of horseradish peroxidase isoenzymes A2 and C were recorded from 2000 to 1800 cm-1. Under alkaline conditions, pH 9, both isoenzymes exhibit two CO stretching bands, at 1938 and 1925 cm-1 for A2 and at 1933 and 1929 cm-1 for C. As the pH is lowered the low-frequency band for each isoenzyme decreases in intensity with a concommitant appearance and increase in intensity of a band at 1906 and 1905 cm-1 for the A2 and C isoenzymes, respectively. These changes conform to pK values of 6.7 for the A2 and 8.8 for the C isoenzymes of horseradish peroxidase. The interpretation of the infrared results was simplified by the observation that a linear relationship exists between the redox potential, Em7, for the FeIII/FeII system vs. the infrared CO stretching frequency, vCO, for cytochrome a3, hemoglobin, myoglobin, and cytochrome P-450 cam with substrate. This relationship suggests that the primary force altering vCO in these heme proteins is a variation in electron density at the heme iron and not direct protein interactions with the CO ligand. The horseradish peroxidase infrared bands in the 1930-cm-1 region correlate well with this relationship. The large deviation of the 1905-cm-1 band from the linear relationship and its dependence upon hydrogen ion concentration are consistent with horseradish peroxidase having a single CO binding site which can hold in two geometries, one of which contains an amino acid moiety capable of forming a hydrogen bond to the carbonyl oxygen."} {"id": "PMID:1276135", "title": "Trifluoroacetylated peptides as substrates and inhibitors of elastase: a nuclear magnetic resonance study.", "content": "Trifluoroacetyl di- and tripeptides have been synthesized in order to investigate their interactions with elastase by proton and fluorine magnetic resonance. These substituted peptides behave as substrates or inhibitors of the enzyme, depending upon their length. They are hydrolyzed with production of trifluoracetic acid and unsubstituted parent peptides exclusively. The amino acid specificity observed and the absence of hydrolysis in the presence of an enzyme substituted at the serine residue of the active site indicate that the trifluoracetic hydrolysis occurs at this site. It requires the fixation of the C-terminal amino acids at the two S' subsites, as does the peptidic hydrolysis of unsubstituted or acetylated oligoalanines. Trifluoracetyl tripeptides exhibit a much higher affinity for the protein, as compared with the unsubstituted or acetylated peptides as well as compared with the trifluoroacetyl dipeptides, and they act as powerful inhibitors of the enzyme. The inhibitory binding mode has been shown to involve the fixation of the trifluoroacetyl group at subsite S4 or in its vicinity, allowing for the cooperative fixation of the C-terminal alanine at S1 and the accommodation of a transproline at S2.", "contents": "Trifluoroacetylated peptides as substrates and inhibitors of elastase: a nuclear magnetic resonance study. Trifluoroacetyl di- and tripeptides have been synthesized in order to investigate their interactions with elastase by proton and fluorine magnetic resonance. These substituted peptides behave as substrates or inhibitors of the enzyme, depending upon their length. They are hydrolyzed with production of trifluoracetic acid and unsubstituted parent peptides exclusively. The amino acid specificity observed and the absence of hydrolysis in the presence of an enzyme substituted at the serine residue of the active site indicate that the trifluoracetic hydrolysis occurs at this site. It requires the fixation of the C-terminal amino acids at the two S' subsites, as does the peptidic hydrolysis of unsubstituted or acetylated oligoalanines. Trifluoracetyl tripeptides exhibit a much higher affinity for the protein, as compared with the unsubstituted or acetylated peptides as well as compared with the trifluoroacetyl dipeptides, and they act as powerful inhibitors of the enzyme. The inhibitory binding mode has been shown to involve the fixation of the trifluoroacetyl group at subsite S4 or in its vicinity, allowing for the cooperative fixation of the C-terminal alanine at S1 and the accommodation of a transproline at S2."} {"id": "PMID:1276136", "title": "Topography of human plasma alpha1-acid glycoprotein.", "content": "Human plasma alpha1-acid glycoprotein, whose linear amino acid sequence has recently been elucidated (Schmid et al. (1973), Biochemistry 12, 2711), was further investigated with regard to its topography. Nitration of this protein and subsequent elucidation of the structures of the peptides containing modified tyrosine indicated that residues 27, 37, 78, 115, 127, and 157 are free, 50 and 91 are in an intermediate state, and 65, 74, 110, and 142 are buried. CD measurements between pH 10 and 12 demonstrated that the buried tyrosines are strongly hydrogen bonded and are probably responsible to a considerable extent for the stability of this protein. Of the three tryptophans of this protein, residue 122 proved to be partially reactive with Koshland reagent while the other two (25 and 160) were found to be unreactive. The state of the two disulfide bonds, established by differential reduction and alkylation with specific reagents, was shown to be of an intermediate type. Using carboxymethylation with bromoacetate at pH 7.0 for 8 days, the three histidines (97, 100, and 171) and methionine 111 could be shown to be in intermediate states. All lysines were treated with trinitrobenzenesulfonate and thus were assumed to be free. Of the 40 carboxylic groups, which were amidated with glycine methyl ester, 32 including the 14 sialyl residues were found to be free, six in an intermediate and the remaining two in a buried state. The present study describes the states of almost half of the amino acid residues of alpha1-acid glycoprotein, a knowledge important for the construction of a preliminary three-dimensional model of this conjugated protein.", "contents": "Topography of human plasma alpha1-acid glycoprotein. Human plasma alpha1-acid glycoprotein, whose linear amino acid sequence has recently been elucidated (Schmid et al. (1973), Biochemistry 12, 2711), was further investigated with regard to its topography. Nitration of this protein and subsequent elucidation of the structures of the peptides containing modified tyrosine indicated that residues 27, 37, 78, 115, 127, and 157 are free, 50 and 91 are in an intermediate state, and 65, 74, 110, and 142 are buried. CD measurements between pH 10 and 12 demonstrated that the buried tyrosines are strongly hydrogen bonded and are probably responsible to a considerable extent for the stability of this protein. Of the three tryptophans of this protein, residue 122 proved to be partially reactive with Koshland reagent while the other two (25 and 160) were found to be unreactive. The state of the two disulfide bonds, established by differential reduction and alkylation with specific reagents, was shown to be of an intermediate type. Using carboxymethylation with bromoacetate at pH 7.0 for 8 days, the three histidines (97, 100, and 171) and methionine 111 could be shown to be in intermediate states. All lysines were treated with trinitrobenzenesulfonate and thus were assumed to be free. Of the 40 carboxylic groups, which were amidated with glycine methyl ester, 32 including the 14 sialyl residues were found to be free, six in an intermediate and the remaining two in a buried state. The present study describes the states of almost half of the amino acid residues of alpha1-acid glycoprotein, a knowledge important for the construction of a preliminary three-dimensional model of this conjugated protein."} {"id": "PMID:1276137", "title": "Anion-induced increases in the rate of colchicine binding to tubulin.", "content": "The rate of binding of colchicine to tubulin to tubulin is enhanced by certain anions. Among the inorganic anions tested, only sulfate was effective. The organic anions include mostly dicarboxylic acids, among which tartrate was the most effective. This effect occurs onlt at low concentrations of colchicine (less than 0.6 X 10(-5) M). The rate increase dor sulfate and L-(+)-tartrate is ca. 2.5-fold at 1.0 mM and plateaus at a limiting value of ca. 4-fold at 100mM. The overall dissociation rate of the colchicine from the complex, which includes both the true rate of dissociation and the rate of irreversible denaturation of tubulin, is not influenced by 1.0 mM tartrate. The affinity constants for colchicine determined from the rate constants are 8.7 X 10(6) and 2.1 X 10(7) M-1 in the absence and the presence of 1.0 mM L-(+)-tartrate. The limiting value is 3.2 X 10(7) M-1. The affinity constant calculated from steady-state measurements is 3.2 X 10(6) M-1 with or without anions. The binding of other ligands like podophyllotoxin, vinblastine, and 1 -anilino-8-naphthalenesulfonate to tubulin is not affected by tartrate. No major conformational changes resulting from anion treatment could be detected by circular dichroism or intrinsic fluorescence. However, the ability of tubulin to polymerize is inhibited by L-(+)-tartrate at concentrations that increase the rate of colchicine binding. We conclude that anions must have a local effect at or near the binding site which enhances the binding rate of colchicine and which may be related to inhibition of polymerization.", "contents": "Anion-induced increases in the rate of colchicine binding to tubulin. The rate of binding of colchicine to tubulin to tubulin is enhanced by certain anions. Among the inorganic anions tested, only sulfate was effective. The organic anions include mostly dicarboxylic acids, among which tartrate was the most effective. This effect occurs onlt at low concentrations of colchicine (less than 0.6 X 10(-5) M). The rate increase dor sulfate and L-(+)-tartrate is ca. 2.5-fold at 1.0 mM and plateaus at a limiting value of ca. 4-fold at 100mM. The overall dissociation rate of the colchicine from the complex, which includes both the true rate of dissociation and the rate of irreversible denaturation of tubulin, is not influenced by 1.0 mM tartrate. The affinity constants for colchicine determined from the rate constants are 8.7 X 10(6) and 2.1 X 10(7) M-1 in the absence and the presence of 1.0 mM L-(+)-tartrate. The limiting value is 3.2 X 10(7) M-1. The affinity constant calculated from steady-state measurements is 3.2 X 10(6) M-1 with or without anions. The binding of other ligands like podophyllotoxin, vinblastine, and 1 -anilino-8-naphthalenesulfonate to tubulin is not affected by tartrate. No major conformational changes resulting from anion treatment could be detected by circular dichroism or intrinsic fluorescence. However, the ability of tubulin to polymerize is inhibited by L-(+)-tartrate at concentrations that increase the rate of colchicine binding. We conclude that anions must have a local effect at or near the binding site which enhances the binding rate of colchicine and which may be related to inhibition of polymerization."} {"id": "PMID:1276138", "title": "Interaction of (3H) bongkrekic acid with the mitochondrial adenine nucleotide translocator.", "content": "Chemical labeling by 3H and biosynthetic labeling by 14C of bongkrekic acid (BA) are described. In the rat liver cell, mitochondria are the only subcellular particles to bind [3H]BA with high affinity. The high affinity sites for BA in mitochondria are located in the inner membrane. High affinity binding sites for BA are only displayed at pH below 7; they amount to 0.15-0.20 nmol/mg of protein in rat liver mitochondria and to 1.1-1.3 nmol/mg of protein in rat heart mitochondria. These values are similar to those found for the high affinity atractyloside binding sites and for the carboxyatractyloside binding sites. The kinetic parameters for BA binding to rat heart mitochondria at 20 degrees C are Kd = 10-40 X 10(-9) M, k+1 = 0.7 X 10(5) M-1 s-1, k-1 = 1.4 X 10(-3) M s-1. Binding assays carried out with rat heart mitochondria, under equilibrium conditions, showed that the amount of BA bound to high affinity sites increases with temperature and reaches the maximum value of 1.1-1.3 nmol/mg of protein at 32-35 degrees C. At lower temperatures, and under equilibrium conditions, a significant fraction of high affinity sites remains masked and is not titrated by BA; these masked BA sites are revealed by addition of micromolar concentrations of ADP or by energization of the mitochondria. Carboxyatractyloside added to rat heart mitochondria preloaded with [3H]BA is able to displace part of the bound [3H]BA. Displacement of the bound BA is enhanced by simultaneous additions of carboxyatractyloside plus ADP, or by energization of the mitochondria. The synergistic effect of carboxyatractyloside and ADP on displacement of bound [3H]BA is also observed in isolated inner membrane vesicles from rat liver mitochondria. When BA is preincubated with rat heart mitochondria before addition of [14C]ADP for assay of ADP transport, the inhibition of ADP transport is a mixed-type inhibition. When BA is preincubated with the mitochondria together with a very small concentration of ADP (less than 0.5 muM), the inhibition of [14C]ADP transport is markedly increased (up to ten times) and it becomes typically uncompetitive, which suggests the formation of a ternary complex, carrier-ADP-BA. The transition from a mixed-type inhibition, with high Ki value, to an uncompetitive type of inhibition, with low Ki value, upon addition of ADP, is explained by an ADP-induced conformational change of the ADP translocator.", "contents": "Interaction of (3H) bongkrekic acid with the mitochondrial adenine nucleotide translocator. Chemical labeling by 3H and biosynthetic labeling by 14C of bongkrekic acid (BA) are described. In the rat liver cell, mitochondria are the only subcellular particles to bind [3H]BA with high affinity. The high affinity sites for BA in mitochondria are located in the inner membrane. High affinity binding sites for BA are only displayed at pH below 7; they amount to 0.15-0.20 nmol/mg of protein in rat liver mitochondria and to 1.1-1.3 nmol/mg of protein in rat heart mitochondria. These values are similar to those found for the high affinity atractyloside binding sites and for the carboxyatractyloside binding sites. The kinetic parameters for BA binding to rat heart mitochondria at 20 degrees C are Kd = 10-40 X 10(-9) M, k+1 = 0.7 X 10(5) M-1 s-1, k-1 = 1.4 X 10(-3) M s-1. Binding assays carried out with rat heart mitochondria, under equilibrium conditions, showed that the amount of BA bound to high affinity sites increases with temperature and reaches the maximum value of 1.1-1.3 nmol/mg of protein at 32-35 degrees C. At lower temperatures, and under equilibrium conditions, a significant fraction of high affinity sites remains masked and is not titrated by BA; these masked BA sites are revealed by addition of micromolar concentrations of ADP or by energization of the mitochondria. Carboxyatractyloside added to rat heart mitochondria preloaded with [3H]BA is able to displace part of the bound [3H]BA. Displacement of the bound BA is enhanced by simultaneous additions of carboxyatractyloside plus ADP, or by energization of the mitochondria. The synergistic effect of carboxyatractyloside and ADP on displacement of bound [3H]BA is also observed in isolated inner membrane vesicles from rat liver mitochondria. When BA is preincubated with rat heart mitochondria before addition of [14C]ADP for assay of ADP transport, the inhibition of ADP transport is a mixed-type inhibition. When BA is preincubated with the mitochondria together with a very small concentration of ADP (less than 0.5 muM), the inhibition of [14C]ADP transport is markedly increased (up to ten times) and it becomes typically uncompetitive, which suggests the formation of a ternary complex, carrier-ADP-BA. The transition from a mixed-type inhibition, with high Ki value, to an uncompetitive type of inhibition, with low Ki value, upon addition of ADP, is explained by an ADP-induced conformational change of the ADP translocator."} {"id": "PMID:1276139", "title": "Isobongkrekic acid, a new inhibitor of mitochondrial ADP-ATP transport: radioactive labeling and chemical and biological properties.", "content": "An isomer of bongkrekic acid, designated as isobongkrekic acid, has been isolated from ethereal extracts of Pseudomonas cocovenenans grown on defatted coconut. Isobongkrekic acid was also obtained by alkaline treatment of bongkrekic acid. Isobongkrekic acid possesses the same ultraviolet spectrum and the same molecular weight as bongkrekic acid; it has a similar infrared spectrum but not the same nuclear magnetic resonance (NMR) spectrum. The differences in NMR data were interpreted to mean that isobongkrekic acid differs from bongkrekic acid by the configuration of the dicarboxylic end; whereas the two carboxylic groups of the dicarboxylic end have the trans configuration in bongkrekic acid, they have the cis configuration in isobongkrekic acid. Differences between bongkrekic and isobongkrekic acids are lost after catalytic hydrogenation of the molecules. Isobongkrekic acid, like bongkrekic acid, is an uncompetitive inhibitor of ADP transport in mitochondria, provided the mitochondria are preincubated in the presence of the inhibitor and a minute concentration of ADP. The inhibitory and binding efficiency of isobongkrekic acid is considerably increased below pH 7. The number of high affinity sites for [3H] isobongkrekic acid is 0.13 to 0.20 nmol/mg protein in rat liver mitochondria and about 1 nmol/mg protein in rat heart mitochondria, i.e., similar to the number of high affinity sites for [3H] bongkrekic acid. Isobongkrekic and bongkrekic acids compete for the same site, but the affinity of isobongkrekic acid for mitochondria is one-half to one-fourth that of bongkrekic acid.", "contents": "Isobongkrekic acid, a new inhibitor of mitochondrial ADP-ATP transport: radioactive labeling and chemical and biological properties. An isomer of bongkrekic acid, designated as isobongkrekic acid, has been isolated from ethereal extracts of Pseudomonas cocovenenans grown on defatted coconut. Isobongkrekic acid was also obtained by alkaline treatment of bongkrekic acid. Isobongkrekic acid possesses the same ultraviolet spectrum and the same molecular weight as bongkrekic acid; it has a similar infrared spectrum but not the same nuclear magnetic resonance (NMR) spectrum. The differences in NMR data were interpreted to mean that isobongkrekic acid differs from bongkrekic acid by the configuration of the dicarboxylic end; whereas the two carboxylic groups of the dicarboxylic end have the trans configuration in bongkrekic acid, they have the cis configuration in isobongkrekic acid. Differences between bongkrekic and isobongkrekic acids are lost after catalytic hydrogenation of the molecules. Isobongkrekic acid, like bongkrekic acid, is an uncompetitive inhibitor of ADP transport in mitochondria, provided the mitochondria are preincubated in the presence of the inhibitor and a minute concentration of ADP. The inhibitory and binding efficiency of isobongkrekic acid is considerably increased below pH 7. The number of high affinity sites for [3H] isobongkrekic acid is 0.13 to 0.20 nmol/mg protein in rat liver mitochondria and about 1 nmol/mg protein in rat heart mitochondria, i.e., similar to the number of high affinity sites for [3H] bongkrekic acid. Isobongkrekic and bongkrekic acids compete for the same site, but the affinity of isobongkrekic acid for mitochondria is one-half to one-fourth that of bongkrekic acid."} {"id": "PMID:1276140", "title": "Kinetics of ATP-dependent Mg2+ flux in mitochondria.", "content": "ATP-dependent Mg2+ accumulation in isolated mitochondria occurs predominantly in the matrix and inner membrane compartments. In mitochondria contaminated with lysosomes, the time course and magnitude of ATP-dependent Mg2+ accumulation are influenced by various cytoplasmic substances, besides substrates of the citric acid cycle. Removal of lysosomes by treatment of the mitochondrial preparation with low concentrations of digitonin, which does not damage the mitoplast, eliminates the modifying influence of cytoplasmic components on Mg2+ flux. In lysosome-free mitochondria, the kinetics of Mg2+ flux is dependent only on the concentration of ATP, of Mg2+, and on the availability of site specific reducing substrates of the electron transport system. Oligomycin at concentrations sufficient to inhibit phosphorylation coupled electron transport and ATP synthesis does not modify Mg2+ flux, which is dependent on added ATP. Site specific inhibitors of the electron transport system inhibit the augmenting effect of oxidizable substrates on Mg2+ uptake, even when electron transfer is inhibited by oligomycin. Atractyloside, by inhibiting the action of externally added ATP, diminishes Mg2+ flux. Ruthenium red is a powerful inhibitor of ATP dependent Mg2+ flux. Uncouplers not only inhibit Mg2+ uptake, but induce Mg2+ efflux. From the time course of Mg2+ flux, a first-order rate constant of egress of Mg2+ and other kinetic constants were calculated and a kinetic model was derived which describes the bi-directional movement of Mg 2+ in mitoplasts.", "contents": "Kinetics of ATP-dependent Mg2+ flux in mitochondria. ATP-dependent Mg2+ accumulation in isolated mitochondria occurs predominantly in the matrix and inner membrane compartments. In mitochondria contaminated with lysosomes, the time course and magnitude of ATP-dependent Mg2+ accumulation are influenced by various cytoplasmic substances, besides substrates of the citric acid cycle. Removal of lysosomes by treatment of the mitochondrial preparation with low concentrations of digitonin, which does not damage the mitoplast, eliminates the modifying influence of cytoplasmic components on Mg2+ flux. In lysosome-free mitochondria, the kinetics of Mg2+ flux is dependent only on the concentration of ATP, of Mg2+, and on the availability of site specific reducing substrates of the electron transport system. Oligomycin at concentrations sufficient to inhibit phosphorylation coupled electron transport and ATP synthesis does not modify Mg2+ flux, which is dependent on added ATP. Site specific inhibitors of the electron transport system inhibit the augmenting effect of oxidizable substrates on Mg2+ uptake, even when electron transfer is inhibited by oligomycin. Atractyloside, by inhibiting the action of externally added ATP, diminishes Mg2+ flux. Ruthenium red is a powerful inhibitor of ATP dependent Mg2+ flux. Uncouplers not only inhibit Mg2+ uptake, but induce Mg2+ efflux. From the time course of Mg2+ flux, a first-order rate constant of egress of Mg2+ and other kinetic constants were calculated and a kinetic model was derived which describes the bi-directional movement of Mg 2+ in mitoplasts."} {"id": "PMID:1276141", "title": "Iodination of a tyrosyl residue in staphylococcal alpha-toxin.", "content": "Iodination of staphylococcal alpha-toxin by the lactoperoxidase method resulted in the maximal incorporation of about 2.5 atoms of iodine per molecule of alpha-toxin. The iodination primarily involved a single tyrosine residue as shown by analysis of both cyanogen bromide and tryptic peptides. Iodination at a level of 1.2 iodine atoms per alpha-toxin molecule led to a dramatic decrease in the hemolytic and lethal activities, although no decrease in the binding of iodinated toxin to rabbit erythrocytes was observed (Cassidy and Harshman (1976), Biochemistry, the following paper in this issue). Monoiodinated alpha-toxin was found to have 15% of the specific hemolytic activity of native alpha-toxin. Incubation of rabbit erythrocytes with iodinated alpha-toxin led to a significant protection from the hemolytic activity of native alpha-toxin added later. The results show the modification of a single unique tyrosyl residue in alpha-toxin permits the resolution of alpha-toxin's biological activities from its cell binding activity.", "contents": "Iodination of a tyrosyl residue in staphylococcal alpha-toxin. Iodination of staphylococcal alpha-toxin by the lactoperoxidase method resulted in the maximal incorporation of about 2.5 atoms of iodine per molecule of alpha-toxin. The iodination primarily involved a single tyrosine residue as shown by analysis of both cyanogen bromide and tryptic peptides. Iodination at a level of 1.2 iodine atoms per alpha-toxin molecule led to a dramatic decrease in the hemolytic and lethal activities, although no decrease in the binding of iodinated toxin to rabbit erythrocytes was observed (Cassidy and Harshman (1976), Biochemistry, the following paper in this issue). Monoiodinated alpha-toxin was found to have 15% of the specific hemolytic activity of native alpha-toxin. Incubation of rabbit erythrocytes with iodinated alpha-toxin led to a significant protection from the hemolytic activity of native alpha-toxin added later. The results show the modification of a single unique tyrosyl residue in alpha-toxin permits the resolution of alpha-toxin's biological activities from its cell binding activity."} {"id": "PMID:1276142", "title": "Studies on the binding of staphylococcal 125I-labeled alpha-toxin to rabbit erythrocytes.", "content": "Staphylococcal alpha-toxin, a hemolytic exotoxin, can be iodinated using the lactoperoxidase method. 125 I-Labeled alpha-toxin binds to rabbit erythrocytes in an apparently irreversible and highly specific manner. The binding of 125 I-labeled alpha-toxin to erythrocytes of rabbit and human reflects the species specificity of native alpha-toxin. Binding of 125I-labeled alpha-toxin is blocked by the presence of native alpha-toxin, 127I-labeled alpha-toxin, or anti-alpha-toxin antibody. Simultaneous assays of 125I-labeled alpha-toxin binding and leakage of intracellular 86Rb+ suggest that toxin binding and membrane damage are separate, sequential functions. Both the rate and extent of binding are temperature dependent. Rabbit erythrocytes possess 5 X 10(3) binding sites/cell, while human erythrocytes possess no detectable binding sites. Treatment of rabbit erythrocytes with 125I-labeled alpha-toxin appears to decrease the number of unoccupied binding sites. Chaotropic ions can inhibit 125I-labeled alpha-toxin binding and cause bound 125I-labeled alpha-toxin to dissociate from rabbit erythrocyte membranes. Treatment of intact rabbit erythrocytes with pronase reduces both the binding capacity of the cells for 125I-labeled alpha-toxin, and the cells' sensitivity to hemolysis by native alpha-toxin. It is proposed that the primary binding site for alpha-toxin in biomembranes is a surface membrane protein.", "contents": "Studies on the binding of staphylococcal 125I-labeled alpha-toxin to rabbit erythrocytes. Staphylococcal alpha-toxin, a hemolytic exotoxin, can be iodinated using the lactoperoxidase method. 125 I-Labeled alpha-toxin binds to rabbit erythrocytes in an apparently irreversible and highly specific manner. The binding of 125 I-labeled alpha-toxin to erythrocytes of rabbit and human reflects the species specificity of native alpha-toxin. Binding of 125I-labeled alpha-toxin is blocked by the presence of native alpha-toxin, 127I-labeled alpha-toxin, or anti-alpha-toxin antibody. Simultaneous assays of 125I-labeled alpha-toxin binding and leakage of intracellular 86Rb+ suggest that toxin binding and membrane damage are separate, sequential functions. Both the rate and extent of binding are temperature dependent. Rabbit erythrocytes possess 5 X 10(3) binding sites/cell, while human erythrocytes possess no detectable binding sites. Treatment of rabbit erythrocytes with 125I-labeled alpha-toxin appears to decrease the number of unoccupied binding sites. Chaotropic ions can inhibit 125I-labeled alpha-toxin binding and cause bound 125I-labeled alpha-toxin to dissociate from rabbit erythrocyte membranes. Treatment of intact rabbit erythrocytes with pronase reduces both the binding capacity of the cells for 125I-labeled alpha-toxin, and the cells' sensitivity to hemolysis by native alpha-toxin. It is proposed that the primary binding site for alpha-toxin in biomembranes is a surface membrane protein."} {"id": "PMID:1276143", "title": "Transbilayer phospholipid asymmetry and its maintenance in the membrane of influenza virus.", "content": "Two phospholipid exchange proteins and two phospholipases C have been employed to determine the phospholipid composition of the outer surface of the membrane of influenza virus. These four protein probes have defined the same accessible and inaccessible pool for each viral phospholipid. Phospholipids which are exchangeable or hydrolyzable are located on the outer surface, whereas the inaccessible pool is located at the inner surface of the viral bilayer. The two pools are unequal in size, with ca. 30% of the total phospholipid accessible to the four proteins, and ca. 70% inaccessible. The membrane is thus highly asymmetric with regard to the amount of phospholipid on each side of the membrane. There is also a marked asymmetry of phospholipid composition. Phosphatidylcholine and phosphatidylinositol are enriched in the outer surface, and sphingomyelim is enriched in the inner surface, whereas phosphatidylethanolamine and phosphatidylserine are present in similar proportions in each surface. This distribution is qualitatively different from that previously reported for the human erythrocyte. The close agreement between results obtained with excahnge proteins and phospholipases C demonstrates that the hydrolytic action of these enzymes does not alter phospholipid asymmetry. The nonperturbing nature of the exchange proteins has permitted the rate of transmembrane movement of phospholipids (flip-flop) in the intact virion to be studied. This process could not be detected after 2 days at 37 degrees C. It was estimated that the half-time for flip-flop is indeterminately in excess of 30 days for sphingomyelin and 10 days for phosphatidylcholine at 37 degrees C. These extremely long times provide a simple explanation for the maintenance of transbilayer asymmetry in influenza virions and possibly, other membranes. Since the viral membrane is acquired by budding through the host cell plasma membrane, the transbilayer distribution of phospholipids observed in the virions presumably reflects a similar asymmetric distribution of phospholipids in the host cell surface membrane. Because animal cells in culture do not incorporate extracellular phospholipid, our results demonstrate that individual cells have the capacity to generate asymmetric membranes.", "contents": "Transbilayer phospholipid asymmetry and its maintenance in the membrane of influenza virus. Two phospholipid exchange proteins and two phospholipases C have been employed to determine the phospholipid composition of the outer surface of the membrane of influenza virus. These four protein probes have defined the same accessible and inaccessible pool for each viral phospholipid. Phospholipids which are exchangeable or hydrolyzable are located on the outer surface, whereas the inaccessible pool is located at the inner surface of the viral bilayer. The two pools are unequal in size, with ca. 30% of the total phospholipid accessible to the four proteins, and ca. 70% inaccessible. The membrane is thus highly asymmetric with regard to the amount of phospholipid on each side of the membrane. There is also a marked asymmetry of phospholipid composition. Phosphatidylcholine and phosphatidylinositol are enriched in the outer surface, and sphingomyelim is enriched in the inner surface, whereas phosphatidylethanolamine and phosphatidylserine are present in similar proportions in each surface. This distribution is qualitatively different from that previously reported for the human erythrocyte. The close agreement between results obtained with excahnge proteins and phospholipases C demonstrates that the hydrolytic action of these enzymes does not alter phospholipid asymmetry. The nonperturbing nature of the exchange proteins has permitted the rate of transmembrane movement of phospholipids (flip-flop) in the intact virion to be studied. This process could not be detected after 2 days at 37 degrees C. It was estimated that the half-time for flip-flop is indeterminately in excess of 30 days for sphingomyelin and 10 days for phosphatidylcholine at 37 degrees C. These extremely long times provide a simple explanation for the maintenance of transbilayer asymmetry in influenza virions and possibly, other membranes. Since the viral membrane is acquired by budding through the host cell plasma membrane, the transbilayer distribution of phospholipids observed in the virions presumably reflects a similar asymmetric distribution of phospholipids in the host cell surface membrane. Because animal cells in culture do not incorporate extracellular phospholipid, our results demonstrate that individual cells have the capacity to generate asymmetric membranes."} {"id": "PMID:1276144", "title": "Acetylcholine receptor oligomers from electroplax of Torpedo species.", "content": "Sedimentation in sucrose gradients of alpha-bungarotoxin-labeled crude and pure acetycholine receptor preparations from Torpedo californica showed two major oligomers. The molecular weights, corrected for the bound Triton X-100 by comparing sedimentation in H2O and in D2O, were 330 000 for the heavy (H) oligomer and 190 000 for the light (L) oligomer. Lesser peaks found in preparations of T. marmorata and purified preparations of T. californica with molecular weights of 500 000 (HH) and 80 000 (LL). These molecular weights are based upon the assumption of globularity, and may require adjustment if the assumption is wrong. The H and L peaks have similar drug sensitivities, but at pH 10 the L peak was stable whereas the H peak dissociated to components sedimenting as LL. Treatments with p-chloromercuribenzoate, which blocks acetylcholine binding partially without affecting alpha-bungarotoxin binding, had no effect upon the pattern of sedimentation. This and other evidence suggested that the heterogeneity of oligomers was unrelated to the heterogeneity of site affinities for acetylcholine and nicotinic drugs.", "contents": "Acetylcholine receptor oligomers from electroplax of Torpedo species. Sedimentation in sucrose gradients of alpha-bungarotoxin-labeled crude and pure acetycholine receptor preparations from Torpedo californica showed two major oligomers. The molecular weights, corrected for the bound Triton X-100 by comparing sedimentation in H2O and in D2O, were 330 000 for the heavy (H) oligomer and 190 000 for the light (L) oligomer. Lesser peaks found in preparations of T. marmorata and purified preparations of T. californica with molecular weights of 500 000 (HH) and 80 000 (LL). These molecular weights are based upon the assumption of globularity, and may require adjustment if the assumption is wrong. The H and L peaks have similar drug sensitivities, but at pH 10 the L peak was stable whereas the H peak dissociated to components sedimenting as LL. Treatments with p-chloromercuribenzoate, which blocks acetylcholine binding partially without affecting alpha-bungarotoxin binding, had no effect upon the pattern of sedimentation. This and other evidence suggested that the heterogeneity of oligomers was unrelated to the heterogeneity of site affinities for acetylcholine and nicotinic drugs."} {"id": "PMID:1276145", "title": "Hydrophobic chromatography and fractionation of enzymes from extremely halophilic bacteria using decreasing concentration gradients of ammonium sulfate.", "content": "Ammonium sulfate fractionation of proteins from extremely halophilic bacteria on Sepharose 4B, carboxymethylcellulose, diethylaminoethylcellulose, and hexamethylenediamine-Agarose is described. Halophilic proteins are absorbed on these gels at 2.5 M ammonium sulfate and eluted by decreasing concentration gradients of this salt. The method has enabled the separation of malate dehydrogenase from glutamate dehydrogenase and aspartate aminotransferase on Sepharose 4B and the additional 15-fold purification of glutamate dehydrogenase on DEAE-cellulose. The technique is simple and convenient, operates at low cost, and possesses great power of resolution. The mechanism of adsorption is discussed and compared to previous instances of \"hydrophobic chromatography\". It is concluded that the retention of halophilic proteins on the polysaccharide gels at 2.5 M ammonium sulfate is due to hydrophobic interactions.", "contents": "Hydrophobic chromatography and fractionation of enzymes from extremely halophilic bacteria using decreasing concentration gradients of ammonium sulfate. Ammonium sulfate fractionation of proteins from extremely halophilic bacteria on Sepharose 4B, carboxymethylcellulose, diethylaminoethylcellulose, and hexamethylenediamine-Agarose is described. Halophilic proteins are absorbed on these gels at 2.5 M ammonium sulfate and eluted by decreasing concentration gradients of this salt. The method has enabled the separation of malate dehydrogenase from glutamate dehydrogenase and aspartate aminotransferase on Sepharose 4B and the additional 15-fold purification of glutamate dehydrogenase on DEAE-cellulose. The technique is simple and convenient, operates at low cost, and possesses great power of resolution. The mechanism of adsorption is discussed and compared to previous instances of \"hydrophobic chromatography\". It is concluded that the retention of halophilic proteins on the polysaccharide gels at 2.5 M ammonium sulfate is due to hydrophobic interactions."} {"id": "PMID:1276146", "title": "Resonance Raman evidence for substrate reorginization in the active site of papain.", "content": "Resonance Raman spectra were obtained for the acylenzyme 4-dimethylamino-3-nitro(alpha-benzamido)cinnamoyl-papain prepared using the chromophoric substrate methyl 4-dimethylamino-3-nitro(alpha-benzamido)cinnamate. These spectra contained vibrational spectral data of the acyl residue while covalently attached to the active site and could be used to follow directly acylation and deacylation kinetics. Spectra were obtained at pH values ranging from those where the acyl-enzyme is relatively stable (pH 3.0, tau 1/2 congruent to 800 s) to those where it is relatively unstable (pH 9.2, tau 1/2 congruent to 223 s). Throughout this range acyl-enzyme spectra differed completely from that of the free substrate or the product (4-dimethylamino-3-nitro(alpha-benzamido)cinnamic acid) indicating that a structural change occurred on combination with the active site. The spectra are consistent with rearrangement of the alpha-benzamido group in the bound substrate, -NH--C(==O)Ph becoming --N==C(--OX)Ph, where the bonding to oxygen is unknown. Superimposed on these large differences, small changes in acyl-enzyme spectra also occurred as pH was raised to decrease the half-life. All of the above spectral perturbations are consistent with a structural change in the acyl-enzyme which precedes the rate-determining step in deacylation. Thus, deacylation proceeds from an acyl residue structure differing from that of the substrate in solution. Upon acid denaturation the spectrum characteristic of the intermediate reverts to one closely resembling the substrate, demonstrating that a functioning active site is necessary to produce the observed differences. Spectra in D2O of native acyl-enzyme were identical with those in H2O, indicating that the observed differences in rate constant were not due to solvent-induced structural changes. Activated papain purified by crystallization or by affinity chromatography formed the acyl-enzyme. However, the kinetics of formation and deacylation differed between these materials, as did the spectral properties. Small differences in active-site structure are considered to be responsible for this effect, and it is suggested that such spectral perturbations may be useful in directly relating small differences in structure of the substrate in the active site with corresponding differences in kinetics.", "contents": "Resonance Raman evidence for substrate reorginization in the active site of papain. Resonance Raman spectra were obtained for the acylenzyme 4-dimethylamino-3-nitro(alpha-benzamido)cinnamoyl-papain prepared using the chromophoric substrate methyl 4-dimethylamino-3-nitro(alpha-benzamido)cinnamate. These spectra contained vibrational spectral data of the acyl residue while covalently attached to the active site and could be used to follow directly acylation and deacylation kinetics. Spectra were obtained at pH values ranging from those where the acyl-enzyme is relatively stable (pH 3.0, tau 1/2 congruent to 800 s) to those where it is relatively unstable (pH 9.2, tau 1/2 congruent to 223 s). Throughout this range acyl-enzyme spectra differed completely from that of the free substrate or the product (4-dimethylamino-3-nitro(alpha-benzamido)cinnamic acid) indicating that a structural change occurred on combination with the active site. The spectra are consistent with rearrangement of the alpha-benzamido group in the bound substrate, -NH--C(==O)Ph becoming --N==C(--OX)Ph, where the bonding to oxygen is unknown. Superimposed on these large differences, small changes in acyl-enzyme spectra also occurred as pH was raised to decrease the half-life. All of the above spectral perturbations are consistent with a structural change in the acyl-enzyme which precedes the rate-determining step in deacylation. Thus, deacylation proceeds from an acyl residue structure differing from that of the substrate in solution. Upon acid denaturation the spectrum characteristic of the intermediate reverts to one closely resembling the substrate, demonstrating that a functioning active site is necessary to produce the observed differences. Spectra in D2O of native acyl-enzyme were identical with those in H2O, indicating that the observed differences in rate constant were not due to solvent-induced structural changes. Activated papain purified by crystallization or by affinity chromatography formed the acyl-enzyme. However, the kinetics of formation and deacylation differed between these materials, as did the spectral properties. Small differences in active-site structure are considered to be responsible for this effect, and it is suggested that such spectral perturbations may be useful in directly relating small differences in structure of the substrate in the active site with corresponding differences in kinetics."} {"id": "PMID:1276147", "title": "The pyridoxal 5' -phosphate site in rabbit skeletal muscle glycogen phosphorylase b: an ultraviolet and 1H and 31P nuclear magnetic resonance spectroscopic study.", "content": "1 H NMR spectra of the 3-0-methylpyridoxal 5'-phosphate-n-butylamine reaction product indicated that this analogue forms a Schiff base in aprotic solvent. The uv spectral properties of 3-0-methylpyridoxal-5'-phosphate phosphorylase b correspond to those of the n-butylamine Schiff base derivative in dimethyl sulfoxide. On the basis of that and auxiliary uv and 1H NMR spectra of pyridoxal and pyridoxal 5'-phosphate and the corresponding Schiff base derivatives we have verified that pyridoxal 5' -phosphate is also bound as a Schiff base to phosphorylase and not as an aldamine. Since 3-0-methylpyridoxal-5'-phosphate phosphorylase is active, a proton shuttle between the 3-hydroxyl group and the pyridine nitrogen is excluded. This directs attention to the 5' -phosphate group of the cofactor as a candidate for a catalytic function. 31P NMR spectra of pyridoxal 5' -phosphate in phosphorylase b indicated that deprotonation of the 5' -phosphate group was unresponsive to external pH. Interaction of phosphorylase b with adenosine 5' -monophosphate, the allosteric effector required activity, and arsenate, which substitutes for phosphate as substrate, triggered a conformational change which resulted in deprotonation of the 5' -phosphate group of pyridoxal 5' at pH 7.6. It now behaved like in the pyridoxal-phosphate-epsilon-aminocaproate Schiff base in aqueous buffer, where the diionized form is dominant at this pH. Differences of line widths of the adenosine 5' -monophosphate signal point to different life times of the allosteric effector- enzyme complexes in the presence and absence of substrate (arsenate).", "contents": "The pyridoxal 5' -phosphate site in rabbit skeletal muscle glycogen phosphorylase b: an ultraviolet and 1H and 31P nuclear magnetic resonance spectroscopic study. 1 H NMR spectra of the 3-0-methylpyridoxal 5'-phosphate-n-butylamine reaction product indicated that this analogue forms a Schiff base in aprotic solvent. The uv spectral properties of 3-0-methylpyridoxal-5'-phosphate phosphorylase b correspond to those of the n-butylamine Schiff base derivative in dimethyl sulfoxide. On the basis of that and auxiliary uv and 1H NMR spectra of pyridoxal and pyridoxal 5'-phosphate and the corresponding Schiff base derivatives we have verified that pyridoxal 5' -phosphate is also bound as a Schiff base to phosphorylase and not as an aldamine. Since 3-0-methylpyridoxal-5'-phosphate phosphorylase is active, a proton shuttle between the 3-hydroxyl group and the pyridine nitrogen is excluded. This directs attention to the 5' -phosphate group of the cofactor as a candidate for a catalytic function. 31P NMR spectra of pyridoxal 5' -phosphate in phosphorylase b indicated that deprotonation of the 5' -phosphate group was unresponsive to external pH. Interaction of phosphorylase b with adenosine 5' -monophosphate, the allosteric effector required activity, and arsenate, which substitutes for phosphate as substrate, triggered a conformational change which resulted in deprotonation of the 5' -phosphate group of pyridoxal 5' at pH 7.6. It now behaved like in the pyridoxal-phosphate-epsilon-aminocaproate Schiff base in aqueous buffer, where the diionized form is dominant at this pH. Differences of line widths of the adenosine 5' -monophosphate signal point to different life times of the allosteric effector- enzyme complexes in the presence and absence of substrate (arsenate)."} {"id": "PMID:1276148", "title": "A DNA binding protein from human placenta specific for ultraviolet damaged DNA.", "content": "A DNA-binding protein specific for ultraviolet irradiated DNA has been purified extensively from human placenta. The binding preparation is free of exonuclease, polymerase, endonuclease, and N-glycosidase activity. The binding activity is salt dependent and is specific for double-stranded irradiated DNA. DNA from which the pyrimidine dimers have been monomerized by the action of photolyase (photoreactivating enzyme) remains an effective substrate for the binding protein, suggesting that the protein recognizes photoproducts other than pyrimidine dimers. This is supported by the finding that DNA irradiated under conditions which introduce only pyrimidine dimers is not a substrate for the binding protein. Examination of three of the xeroderma pigmentosum complementation groups has revealed no deficiency in this binding activity.", "contents": "A DNA binding protein from human placenta specific for ultraviolet damaged DNA. A DNA-binding protein specific for ultraviolet irradiated DNA has been purified extensively from human placenta. The binding preparation is free of exonuclease, polymerase, endonuclease, and N-glycosidase activity. The binding activity is salt dependent and is specific for double-stranded irradiated DNA. DNA from which the pyrimidine dimers have been monomerized by the action of photolyase (photoreactivating enzyme) remains an effective substrate for the binding protein, suggesting that the protein recognizes photoproducts other than pyrimidine dimers. This is supported by the finding that DNA irradiated under conditions which introduce only pyrimidine dimers is not a substrate for the binding protein. Examination of three of the xeroderma pigmentosum complementation groups has revealed no deficiency in this binding activity."} {"id": "PMID:1276149", "title": "A mammalian nicking endonuclease.", "content": "Purification and properties are described for an endonuclease isolated from calf thymus which attacks double-stranded, unmodified DNA, primarily by making single-strand breaks. No detectable acid-soluble products arise from the reaction. Double-strand breaks may occasionally be produced by the introduction of single-strand breaks on opposite strands in close proximity. The enzyme does not attack denatured DNA and is not inhibited by tRNA. Although added divalent cations are not required for activity, the enzyme is inhibited by EDTA, which suggests an essential role for bound cations; reaction is inhibited by Ca2+. The endonuclease has a broad pH optimum and is inactivated by preincubation at temperatures of 45 degrees C and higher. The molecular weight as determined by gel chromatography is about 30 000. Analysis of the products of reaction on a defined substrate, bacteriophage T3 DNA, by sedimentation in alkaline sucrose density gradients indicates limit products with chain lengths of about 0.8 X 10(6) daltons. On electrophoresis in agarose gels these products were shown to be heterogeneous in size. The endonuclease appears to generate 3'-hydroxyl and 5'-phosphate ends. The ability of the endonuclease to utilize bovine DNA as substrate argues against a restriction role for this enzyme.", "contents": "A mammalian nicking endonuclease. Purification and properties are described for an endonuclease isolated from calf thymus which attacks double-stranded, unmodified DNA, primarily by making single-strand breaks. No detectable acid-soluble products arise from the reaction. Double-strand breaks may occasionally be produced by the introduction of single-strand breaks on opposite strands in close proximity. The enzyme does not attack denatured DNA and is not inhibited by tRNA. Although added divalent cations are not required for activity, the enzyme is inhibited by EDTA, which suggests an essential role for bound cations; reaction is inhibited by Ca2+. The endonuclease has a broad pH optimum and is inactivated by preincubation at temperatures of 45 degrees C and higher. The molecular weight as determined by gel chromatography is about 30 000. Analysis of the products of reaction on a defined substrate, bacteriophage T3 DNA, by sedimentation in alkaline sucrose density gradients indicates limit products with chain lengths of about 0.8 X 10(6) daltons. On electrophoresis in agarose gels these products were shown to be heterogeneous in size. The endonuclease appears to generate 3'-hydroxyl and 5'-phosphate ends. The ability of the endonuclease to utilize bovine DNA as substrate argues against a restriction role for this enzyme."} {"id": "PMID:1276150", "title": "Relationship between nuclear and cytoplasmic RNA in Drosophilia cells.", "content": "Polyadenylated RNA was isolated from nuclei of cultured Drosophila cells, Schneider's line 2, and used as a template to synthesize a complementary DNA probe. Hybridization experiments were performed to study the relationship between nuclear and cytoplasmic RNA. About two-thirds of the nuclear polyadenylated RNA sequences exist in the cytoplasm. Experiments with fractionated cDNA probes demonstrated that RNA sequences that are frequent in the nucleus are also abundant in the cytoplasm. These findings are consistent with a precursor-product relationship in which some polyadenylated molecules in the nucleus are destined for the cytoplasm while other sequences are polyadenylated but not transferred.", "contents": "Relationship between nuclear and cytoplasmic RNA in Drosophilia cells. Polyadenylated RNA was isolated from nuclei of cultured Drosophila cells, Schneider's line 2, and used as a template to synthesize a complementary DNA probe. Hybridization experiments were performed to study the relationship between nuclear and cytoplasmic RNA. About two-thirds of the nuclear polyadenylated RNA sequences exist in the cytoplasm. Experiments with fractionated cDNA probes demonstrated that RNA sequences that are frequent in the nucleus are also abundant in the cytoplasm. These findings are consistent with a precursor-product relationship in which some polyadenylated molecules in the nucleus are destined for the cytoplasm while other sequences are polyadenylated but not transferred."} {"id": "PMID:1276151", "title": "Metabolism of 1,25-dihydroxyvitamin D3: evidence for side-chain oxidation.", "content": "Approximately 7% of a 650-pmol dose of 25-hydroxyl[26,27-14C]vitamin D3 and 25% of a 325-pmol dose of 1,25-dihydroxyl[26,27-14C]vitamin D3 are metabolized to 14CO2 by vitamin D deficient rats. Nephrectomy prevents the metabolism of 25-hydroxy[26,27-14C]vitamin D3 to 14CO2 but not that of 1,25-dihydroxy[26,27-14C]vitamin D3. Less than 5% of the 14C from 24,25-dihydroxy[26,27-14C]vitamin D3 is metabolized to 14CO2. Feeding diets high in calcium and supplemented with vitamin D3 markedly diminishes the amount of 14CO2 formed from 25-hydroxy[26,27-14C]vitamin D3 but not that from 1,25-dihydroxyl[26,27-14C]vitamin D3. These results provide strong evidence that only 1-hydroxylated vitamin D compounds and especially 1,25-dihydroxyvitamin D3 undergo side-chain oxidation and cleavage to yield an unknown metabolite and CO2.", "contents": "Metabolism of 1,25-dihydroxyvitamin D3: evidence for side-chain oxidation. Approximately 7% of a 650-pmol dose of 25-hydroxyl[26,27-14C]vitamin D3 and 25% of a 325-pmol dose of 1,25-dihydroxyl[26,27-14C]vitamin D3 are metabolized to 14CO2 by vitamin D deficient rats. Nephrectomy prevents the metabolism of 25-hydroxy[26,27-14C]vitamin D3 to 14CO2 but not that of 1,25-dihydroxy[26,27-14C]vitamin D3. Less than 5% of the 14C from 24,25-dihydroxy[26,27-14C]vitamin D3 is metabolized to 14CO2. Feeding diets high in calcium and supplemented with vitamin D3 markedly diminishes the amount of 14CO2 formed from 25-hydroxy[26,27-14C]vitamin D3 but not that from 1,25-dihydroxyl[26,27-14C]vitamin D3. These results provide strong evidence that only 1-hydroxylated vitamin D compounds and especially 1,25-dihydroxyvitamin D3 undergo side-chain oxidation and cleavage to yield an unknown metabolite and CO2."} {"id": "PMID:1276152", "title": "Polymorphism of Sporothrix schenckii surface polysaccharides as a function of morphological differentiation.", "content": "The alkali-extractable polysaccharides from different morphological types of two Sporothrix schenckii strains (1099.12 and 1099.18) were investigated. Dissociation of morphological phase transition and temperature effects was possible in a synthetic medium which produced cultures with 100% yeast forms either at 25 or at 37 degrees C. Only rhamnomannans with single-unit alpha-L-rhamnopyranosyl side chains were formed by the yeast forms irrespective of the incubation temperature. The higher temperature inhibited formation of 4-O- and 2,4-di-O-substituted alpha-D-mannopyranose units in the rhamnomannan. An apparently unsporulated mycelium culture of one S. schenckii strain (1099.12) synthesized a galactomannan whose structure was partially determined by methylation analysis and by proton and 13C nuclear magnetic resonance spectroscopy. In another strain (1099.18), a mannan was excreted in the medium of an apparently conidia-less mycelial form at 25 degrees C with short incubation. Its structure was also partially determined. An apparent mixture of this mannan and a rhamnomannan rich in alpha-L-rhamnopyranosyl-(1 leads to 2)-alpha-L-rhamnopyranose side chains formed in these cultures on prolonged incubation. The proportion of the excreted rhamnomannan increased as the mycelium sporulated and conidia were more numerous. Mannans or galactomannans may be transient polysaccharides in the young mycelium of S. schenckii. As the culture develops, rhamnomannans are formed in amounts usually masking the presence of other mannose-containing polysaccharides. It is suggested that in S. schenckii different polysaccharides are formed with side chains containing different proportions of rhamnose, mannose, or galactose, as a function of morphological differentiation.", "contents": "Polymorphism of Sporothrix schenckii surface polysaccharides as a function of morphological differentiation. The alkali-extractable polysaccharides from different morphological types of two Sporothrix schenckii strains (1099.12 and 1099.18) were investigated. Dissociation of morphological phase transition and temperature effects was possible in a synthetic medium which produced cultures with 100% yeast forms either at 25 or at 37 degrees C. Only rhamnomannans with single-unit alpha-L-rhamnopyranosyl side chains were formed by the yeast forms irrespective of the incubation temperature. The higher temperature inhibited formation of 4-O- and 2,4-di-O-substituted alpha-D-mannopyranose units in the rhamnomannan. An apparently unsporulated mycelium culture of one S. schenckii strain (1099.12) synthesized a galactomannan whose structure was partially determined by methylation analysis and by proton and 13C nuclear magnetic resonance spectroscopy. In another strain (1099.18), a mannan was excreted in the medium of an apparently conidia-less mycelial form at 25 degrees C with short incubation. Its structure was also partially determined. An apparent mixture of this mannan and a rhamnomannan rich in alpha-L-rhamnopyranosyl-(1 leads to 2)-alpha-L-rhamnopyranose side chains formed in these cultures on prolonged incubation. The proportion of the excreted rhamnomannan increased as the mycelium sporulated and conidia were more numerous. Mannans or galactomannans may be transient polysaccharides in the young mycelium of S. schenckii. As the culture develops, rhamnomannans are formed in amounts usually masking the presence of other mannose-containing polysaccharides. It is suggested that in S. schenckii different polysaccharides are formed with side chains containing different proportions of rhamnose, mannose, or galactose, as a function of morphological differentiation."} {"id": "PMID:1276153", "title": "A calorimetric study of the thermotropic behavior of aqueous dispersions of natural and synthetic sphingomyelins.", "content": "A recently developed differential scanning calorimeter has been used to characterize the thermotropic behavior of aqueous dispersions of liposomes containing sphingomyelin. Liposomes derived from sheep brain sphingomyelin exhibit a broad gel-liquid crystalline phase transition in the temperature range of 20-45 degrees C. The transition is characterized by maxima in the heat capacity function at 31.2 and 37.1 degrees C and a total enthalpy change of 7.2 +/-0.4 kcal/mol. Beef brain sphingomyelin liposomes behave similarly but exhibit heat capacity maxima at 30, 32, and 38 degrees C and a total enthalpy change of 6.9 kcal/mol. The thermotropic behavior of four pure synthetic sphingomyelins is reminiscent of multilamellar lecithin liposomes in that a single, sharp, main transition is observed. Results obtained for liposomes containing mixtures of different sphingomyelins are complex. A colyophilized mixture of N-palmitoylsphingosinephosphorylcholine, N-stearoylsphingosinephosphorylcholine, and N-lignocerylsphingosinephosphorylcholine in a 1 : 1 : 1 mol ratio exhibits a single transition with a Tm below that observed for the individual components. On the other hand a 1 : 1 mixture of N-stearoylsphingosinephosphorylcholine and 1-palmitoyl-2-oleylphosphatidylcholine exhibits three maxima in the heat capacity function. It is clear from these results that the thermotropic behavior of sphingomyelin-containing liposomes is a complex function of the exact composition. Furthermore, it appears that the behavior of the liposomes derived from natural sphingomyelins cannot be explained in terms of phase separation of the individual components.", "contents": "A calorimetric study of the thermotropic behavior of aqueous dispersions of natural and synthetic sphingomyelins. A recently developed differential scanning calorimeter has been used to characterize the thermotropic behavior of aqueous dispersions of liposomes containing sphingomyelin. Liposomes derived from sheep brain sphingomyelin exhibit a broad gel-liquid crystalline phase transition in the temperature range of 20-45 degrees C. The transition is characterized by maxima in the heat capacity function at 31.2 and 37.1 degrees C and a total enthalpy change of 7.2 +/-0.4 kcal/mol. Beef brain sphingomyelin liposomes behave similarly but exhibit heat capacity maxima at 30, 32, and 38 degrees C and a total enthalpy change of 6.9 kcal/mol. The thermotropic behavior of four pure synthetic sphingomyelins is reminiscent of multilamellar lecithin liposomes in that a single, sharp, main transition is observed. Results obtained for liposomes containing mixtures of different sphingomyelins are complex. A colyophilized mixture of N-palmitoylsphingosinephosphorylcholine, N-stearoylsphingosinephosphorylcholine, and N-lignocerylsphingosinephosphorylcholine in a 1 : 1 : 1 mol ratio exhibits a single transition with a Tm below that observed for the individual components. On the other hand a 1 : 1 mixture of N-stearoylsphingosinephosphorylcholine and 1-palmitoyl-2-oleylphosphatidylcholine exhibits three maxima in the heat capacity function. It is clear from these results that the thermotropic behavior of sphingomyelin-containing liposomes is a complex function of the exact composition. Furthermore, it appears that the behavior of the liposomes derived from natural sphingomyelins cannot be explained in terms of phase separation of the individual components."} {"id": "PMID:1276154", "title": "Interactions between anesthetics and lipid mixtures. Normal alcohols.", "content": "The effects of normal alcohols up to 1-dodecanol on phase transitions in phosphatidylcholines and phosphatidylethanolamines have been studied using chlorophyll a as fluorescent probe. With the phosphatidylcholines, alcohols up to octanol cause a lowering of the transition temperature, and a broadening of the transition, whereas for dipalmitoylphosphatidylethanolamine, only a lowering of the transition is observed. The lowering of the phase transition temperature in dipalmitoylphosphatidylcholine by butanol and hexanol is close to that expected for ideal behavior, but the behavior of the longer chain alcohols becomes less ideal. The effects of these alcohols on mixtures of lipids have been studied, and they illustrate the care necessary if these plots of temperatures of onset and completion of gel phase formation are to be called \"phase diagrams\". The effect of 1 -octanol on mixtures of lipids is to increase the proportion of lipid present in the lipid-crystalline state. In contrast, 1-decanol causes an increase in the phase transition temperature for dimyristoylphosphatidylcholine, although it lowers the transition temperature for dipalmitoylphosphatidylcholine, and 1 -dodecanol raises the transition temperature for both of these phosphatidylcholines, although it lowers that for dipalmitoylphosphatidylethanolamine. Dodecanol appears to behave in these lipid bilayer membranes as a lipid with a phase transition temperature of ca. 55 degrees C. Anesthesia is discussed as a phenomenon of liquidus extension: alcohols up to 1 -octanol increase the proportion of lipid in the liquidus state and result in anesthesia, whereas the longer alcohols do not, and result in catalepsy.", "contents": "Interactions between anesthetics and lipid mixtures. Normal alcohols. The effects of normal alcohols up to 1-dodecanol on phase transitions in phosphatidylcholines and phosphatidylethanolamines have been studied using chlorophyll a as fluorescent probe. With the phosphatidylcholines, alcohols up to octanol cause a lowering of the transition temperature, and a broadening of the transition, whereas for dipalmitoylphosphatidylethanolamine, only a lowering of the transition is observed. The lowering of the phase transition temperature in dipalmitoylphosphatidylcholine by butanol and hexanol is close to that expected for ideal behavior, but the behavior of the longer chain alcohols becomes less ideal. The effects of these alcohols on mixtures of lipids have been studied, and they illustrate the care necessary if these plots of temperatures of onset and completion of gel phase formation are to be called \"phase diagrams\". The effect of 1 -octanol on mixtures of lipids is to increase the proportion of lipid present in the lipid-crystalline state. In contrast, 1-decanol causes an increase in the phase transition temperature for dimyristoylphosphatidylcholine, although it lowers the transition temperature for dipalmitoylphosphatidylcholine, and 1 -dodecanol raises the transition temperature for both of these phosphatidylcholines, although it lowers that for dipalmitoylphosphatidylethanolamine. Dodecanol appears to behave in these lipid bilayer membranes as a lipid with a phase transition temperature of ca. 55 degrees C. Anesthesia is discussed as a phenomenon of liquidus extension: alcohols up to 1 -octanol increase the proportion of lipid in the liquidus state and result in anesthesia, whereas the longer alcohols do not, and result in catalepsy."} {"id": "PMID:1276155", "title": "Intramolecular microdynamical and conformational parameters of peptides from 1H and 13C NMR spin-lattice relaxation. Tetragastrin.", "content": "Measurements of 1H and 13C spin-lattice relaxation and 13C nuclear Overhauser enhancement factors are reported for dimethyl sulfoxide solutions of tetragastrin, a pharmacologically active tetrapeptide. The use of the dipolar formalism for predicting 1H and quaternary 13C relaxation rates is discussed. Furthermore, the prospect is opened for the use of quaternary 13C and 1H relaxation times to obtain information on the peptide torsion angles phi, psi, and chi in a way supplementing NMR coupling constant methods presently in use.", "contents": "Intramolecular microdynamical and conformational parameters of peptides from 1H and 13C NMR spin-lattice relaxation. Tetragastrin. Measurements of 1H and 13C spin-lattice relaxation and 13C nuclear Overhauser enhancement factors are reported for dimethyl sulfoxide solutions of tetragastrin, a pharmacologically active tetrapeptide. The use of the dipolar formalism for predicting 1H and quaternary 13C relaxation rates is discussed. Furthermore, the prospect is opened for the use of quaternary 13C and 1H relaxation times to obtain information on the peptide torsion angles phi, psi, and chi in a way supplementing NMR coupling constant methods presently in use."} {"id": "PMID:1276156", "title": "Dual labeling in standard DNA-RNA hybridization studies using 125 I-labeled nuclear RNA and 3H-labeled DNA.", "content": "Standard DNA-RNA hybridization studies, using nucleic acids isolated from mammalian tissues, are frequently hindered by relatively low levels of radioactivity in pulse-labeled RNA and in an inability to reliably estimate the amount of DNA present in the hybrid. In the method described here nuclear RNA is labeled in vitro with 125I to 400 000- 800 000 cpm/mug and DNA is obtained from a rat glial tumor line grown in culture and labeled to specific activities of 42 000-79 000 cpm/mug. DNA-RNA hybridization is conducted in an all solution system at RNA:DNA ratios of 3.5:1 to 18:1. Assay background is controlled by pretreatment of the hybrid and free RNA at the conclusion of the annealing study with RNase, then isolation of the hybrid together with a small fraction of free RNA oligonucleotides on hydroxyapatite. The partially purified hybrids are then trapped on Millipore filters. Assay background id 0.004% of total counts present in the annealing reaction. Comparison of the annealing reactions of pulse-labeled liver nuclear RNA and in vitro 125I-labeled nuclear RNA in saturation, kinetic, and competitive hybridization studies shows them to be essentially the same. Nuclear RNA labeled by either tritium or iodine shows a 10-20-fold greater concentration of the annealing sequences over that found in the microsomal RNA. Minor differences are noted between the nuclear RNAs in the initial rates of reaction and in the magnitude of the decrease in percent hybridization at low levels of unlabeled competitor RNA. This may be due to preferential labeling in pulse-labeled RNA of molecules which are present in lower concentrations or are transcribed from more frequently repeated DNA sequences than the average population of annealing RNA molecules. The technique has application in systems where the amount of tissue for RNA extraction is small or where the system does not permit the obtaining of pulse-labeled RNA, as in experimental rodent skin carcinogenesis or in dealing with RNA from the tissues of large mammals or humans.", "contents": "Dual labeling in standard DNA-RNA hybridization studies using 125 I-labeled nuclear RNA and 3H-labeled DNA. Standard DNA-RNA hybridization studies, using nucleic acids isolated from mammalian tissues, are frequently hindered by relatively low levels of radioactivity in pulse-labeled RNA and in an inability to reliably estimate the amount of DNA present in the hybrid. In the method described here nuclear RNA is labeled in vitro with 125I to 400 000- 800 000 cpm/mug and DNA is obtained from a rat glial tumor line grown in culture and labeled to specific activities of 42 000-79 000 cpm/mug. DNA-RNA hybridization is conducted in an all solution system at RNA:DNA ratios of 3.5:1 to 18:1. Assay background is controlled by pretreatment of the hybrid and free RNA at the conclusion of the annealing study with RNase, then isolation of the hybrid together with a small fraction of free RNA oligonucleotides on hydroxyapatite. The partially purified hybrids are then trapped on Millipore filters. Assay background id 0.004% of total counts present in the annealing reaction. Comparison of the annealing reactions of pulse-labeled liver nuclear RNA and in vitro 125I-labeled nuclear RNA in saturation, kinetic, and competitive hybridization studies shows them to be essentially the same. Nuclear RNA labeled by either tritium or iodine shows a 10-20-fold greater concentration of the annealing sequences over that found in the microsomal RNA. Minor differences are noted between the nuclear RNAs in the initial rates of reaction and in the magnitude of the decrease in percent hybridization at low levels of unlabeled competitor RNA. This may be due to preferential labeling in pulse-labeled RNA of molecules which are present in lower concentrations or are transcribed from more frequently repeated DNA sequences than the average population of annealing RNA molecules. The technique has application in systems where the amount of tissue for RNA extraction is small or where the system does not permit the obtaining of pulse-labeled RNA, as in experimental rodent skin carcinogenesis or in dealing with RNA from the tissues of large mammals or humans."} {"id": "PMID:1276157", "title": "Calculation of s20,w values using ultracentrifuge sedimentation data from linear sucrose gradients, an improved, simplified method.", "content": "A mathematical method is described for calculating the sedimentation coefficient (S20,W) with ultracentrifuge data from linear sucrose gradients. Gradient density and viscosity functions are precisely described by regression equations, which permit continuous evaluation (by integration) of the effects of gradient geometry on particle sedimentation. The results agree with previously used and more complex methods.", "contents": "Calculation of s20,w values using ultracentrifuge sedimentation data from linear sucrose gradients, an improved, simplified method. A mathematical method is described for calculating the sedimentation coefficient (S20,W) with ultracentrifuge data from linear sucrose gradients. Gradient density and viscosity functions are precisely described by regression equations, which permit continuous evaluation (by integration) of the effects of gradient geometry on particle sedimentation. The results agree with previously used and more complex methods."} {"id": "PMID:1276158", "title": "Protein-polynucleotide scattering centers as a protein structure probe.", "content": "When certain basic globular proteins are mixed with nucleic acids near a critical concentration ratio, large, low density scattering centers of about 10(9) particle weight are created. Scattering from these complexes is altered when thermally inactivated proteins are substituted for enzymes in their native, globular conformation. Scattering data from heat-treated ribonuclease and lysozyme mixed with four different synthetic homopolyribonucleotides are reported. The concentration of nucleic acid necessary to produce maximum scattering from a heat-treated protein sample is shown to be a direct indication of the amount of enzyme that remains biologically active after being heated.", "contents": "Protein-polynucleotide scattering centers as a protein structure probe. When certain basic globular proteins are mixed with nucleic acids near a critical concentration ratio, large, low density scattering centers of about 10(9) particle weight are created. Scattering from these complexes is altered when thermally inactivated proteins are substituted for enzymes in their native, globular conformation. Scattering data from heat-treated ribonuclease and lysozyme mixed with four different synthetic homopolyribonucleotides are reported. The concentration of nucleic acid necessary to produce maximum scattering from a heat-treated protein sample is shown to be a direct indication of the amount of enzyme that remains biologically active after being heated."} {"id": "PMID:1276159", "title": "Low temperature photodissociation studies of ferrous hemoglobin and myoglobin complexes by M\u00f6ssbauer spectroscopy.", "content": "57Fe-enriched complexes of hemoglobin and myoglobin with CO and O2 were photodissociated at 4.2 degrees K, and the resulting spectra were compared with those of the deoxy forms. Differences in both quadrupole splitting and isomer shift were noted for each protein, the photoproducts having smaller isomer shift and larger quadrupole splitting than the deoxy forms. The photoproducts of HbCO and HbO2 had narrow absorption lines, indicating a well-defined iron environment. The corresponding myoglobin species had broader absorption lines, as did both deoxy forms. The weak absorption lines of photodissociated NO complexes appeared to be wide, possibly indicating magnetic interaction with the unpaired electron of the nearby NO.", "contents": "Low temperature photodissociation studies of ferrous hemoglobin and myoglobin complexes by M\u00f6ssbauer spectroscopy. 57Fe-enriched complexes of hemoglobin and myoglobin with CO and O2 were photodissociated at 4.2 degrees K, and the resulting spectra were compared with those of the deoxy forms. Differences in both quadrupole splitting and isomer shift were noted for each protein, the photoproducts having smaller isomer shift and larger quadrupole splitting than the deoxy forms. The photoproducts of HbCO and HbO2 had narrow absorption lines, indicating a well-defined iron environment. The corresponding myoglobin species had broader absorption lines, as did both deoxy forms. The weak absorption lines of photodissociated NO complexes appeared to be wide, possibly indicating magnetic interaction with the unpaired electron of the nearby NO."} {"id": "PMID:1276160", "title": "Water proton magnetic resonance studies of normal and sickle erythrocytes. Temperature and volume dependence.", "content": "The temperature and cell volume dependence of the NMR water proton line-width, spin-lattice, and spin-spin relaxation times have been studied for normal and sickle erythrocytes as well as hemoglobin A and hemoglobin S solutions. Upon deoxygenation, the spin-spin relaxation time (T2) decreases by a factor of 2 for sickle cells and hemoglobin S solutions but remains relatively constant for normal cells and hemoglobin A solutions. The spin-lattice relaxation time (T1) shows no significant change upon deoxygenation for normal or sickle packed red cells. Studies of the change in the NMR linewidth, T1 and T2 as the cell hydration is changed indicate that these parameters are affected only slightly by a 10-20% cell dehydration. This result suggests that the reported 10% cell dehydration observed with sickling is not important in the altered NMR properties. Low temperature studies of the linewidth and T1 for oxy and deoxy hemoglobin A and hemoglobin S solutions suggest that the \"bound\" water possesses similar properties for all four species. The low temperature linewidth ranges from about 250 Hz at -15 degrees C to 500 Hz at -36 degrees C and analysis of the NMR curves yield hydration values near 0.4 g water/g hemoglobin for all four species. The low temperature T1 data go through a minimum at -35 degrees C for measurements at 44.4 MHz and -50 degrees C for measurements at 17.1 MHz and are similar for oxy and deoxy hemoglobin A and hemoglobin S. These similarities in the low temperature NMR data for oxy and deoxy hemoglobin A and hemoglobin S suggest a hydrophobically driven sickling mechanism. The room temperature and low temperature relaxation time data for normal and sickle cells are interpreted in terms of a three-state model for intracellular water. In the context of this model the relaxation time data imply that type III, or irrotationally bound water, is altered during the sickling process.", "contents": "Water proton magnetic resonance studies of normal and sickle erythrocytes. Temperature and volume dependence. The temperature and cell volume dependence of the NMR water proton line-width, spin-lattice, and spin-spin relaxation times have been studied for normal and sickle erythrocytes as well as hemoglobin A and hemoglobin S solutions. Upon deoxygenation, the spin-spin relaxation time (T2) decreases by a factor of 2 for sickle cells and hemoglobin S solutions but remains relatively constant for normal cells and hemoglobin A solutions. The spin-lattice relaxation time (T1) shows no significant change upon deoxygenation for normal or sickle packed red cells. Studies of the change in the NMR linewidth, T1 and T2 as the cell hydration is changed indicate that these parameters are affected only slightly by a 10-20% cell dehydration. This result suggests that the reported 10% cell dehydration observed with sickling is not important in the altered NMR properties. Low temperature studies of the linewidth and T1 for oxy and deoxy hemoglobin A and hemoglobin S solutions suggest that the \"bound\" water possesses similar properties for all four species. The low temperature linewidth ranges from about 250 Hz at -15 degrees C to 500 Hz at -36 degrees C and analysis of the NMR curves yield hydration values near 0.4 g water/g hemoglobin for all four species. The low temperature T1 data go through a minimum at -35 degrees C for measurements at 44.4 MHz and -50 degrees C for measurements at 17.1 MHz and are similar for oxy and deoxy hemoglobin A and hemoglobin S. These similarities in the low temperature NMR data for oxy and deoxy hemoglobin A and hemoglobin S suggest a hydrophobically driven sickling mechanism. The room temperature and low temperature relaxation time data for normal and sickle cells are interpreted in terms of a three-state model for intracellular water. In the context of this model the relaxation time data imply that type III, or irrotationally bound water, is altered during the sickling process."} {"id": "PMID:1276161", "title": "Water diffusion permeability of human erythrocytes studied by a pulsed gradient NMR technique.", "content": "Water diffusion permeability of human erythrocytes has been measured by NMR using a pulsed magnetic field gradient technique. The measurement of exchange rates was based on restricted diffusion of water molecules within red blood cells. This method avoids addition of paramagnetic ions, such as Mn2+, and is used in vivo. The mean lifetime of water insed human erythrocytes was found to be 17 ms at 24 degrees C. A sulfhydryl reagent, known to inhibit water osmotic permeability, reduced significantly water diffusion across the red cell membrane.", "contents": "Water diffusion permeability of human erythrocytes studied by a pulsed gradient NMR technique. Water diffusion permeability of human erythrocytes has been measured by NMR using a pulsed magnetic field gradient technique. The measurement of exchange rates was based on restricted diffusion of water molecules within red blood cells. This method avoids addition of paramagnetic ions, such as Mn2+, and is used in vivo. The mean lifetime of water insed human erythrocytes was found to be 17 ms at 24 degrees C. A sulfhydryl reagent, known to inhibit water osmotic permeability, reduced significantly water diffusion across the red cell membrane."} {"id": "PMID:1276162", "title": "Chemical reactivity of labile sulfur of iron-sulfur proteins. The reaction of triphenyl phosphine.", "content": "The reaction of triphenyl phosphine to iron-sulfur proteins from adrenal cortex mitochondria, spinach chloroplasts, and Clostridium pasteurianum was investigated. As ethanol concentrations in the reaction mixture increased, the rate of the reaction decreased. In the simultaneous presence of 1 M KC1 and 5 M urea, the reaction rate reached at maximum. Under these conditions the initial rates of the decolorization reaction by the phosphine were found to be 8.7, 0.88, and 1.8 nmol of ferredoxin per min at 25 degrees C for adrenal, spinach, and clostridial ferredoxins, respectively. The kinetic curves for the reaction of the phosphine sulfide formation, the loss of labile sulfur, and the deterioriation of visible absorption showed a similar pattern with a comparable rate. During this reaction, the complete reduction of ferric ions present in ferredoxin was observed with a fast rate under either aerobic or anaerobic conditions. These results suggest that the iron atoms in ferredoxin are first reduced by the intramolecular reductants in the presence of triphenyl phosphine with the concomitant formation of S2-2, which then reacts with triphenyl phosphine resulting in the formation of triphenyl phosphine sulfide.", "contents": "Chemical reactivity of labile sulfur of iron-sulfur proteins. The reaction of triphenyl phosphine. The reaction of triphenyl phosphine to iron-sulfur proteins from adrenal cortex mitochondria, spinach chloroplasts, and Clostridium pasteurianum was investigated. As ethanol concentrations in the reaction mixture increased, the rate of the reaction decreased. In the simultaneous presence of 1 M KC1 and 5 M urea, the reaction rate reached at maximum. Under these conditions the initial rates of the decolorization reaction by the phosphine were found to be 8.7, 0.88, and 1.8 nmol of ferredoxin per min at 25 degrees C for adrenal, spinach, and clostridial ferredoxins, respectively. The kinetic curves for the reaction of the phosphine sulfide formation, the loss of labile sulfur, and the deterioriation of visible absorption showed a similar pattern with a comparable rate. During this reaction, the complete reduction of ferric ions present in ferredoxin was observed with a fast rate under either aerobic or anaerobic conditions. These results suggest that the iron atoms in ferredoxin are first reduced by the intramolecular reductants in the presence of triphenyl phosphine with the concomitant formation of S2-2, which then reacts with triphenyl phosphine resulting in the formation of triphenyl phosphine sulfide."} {"id": "PMID:1276163", "title": "Studies on cephalopod rhodopsin: photoisomerization of the chromophore.", "content": "Photoisomerization of the chromophore of squid rhodopsin is dependent upon the irradiation temperature. Above 0 degrees C, only 11-cis in equilibrium all-trans reaction proceeds and the all-trans leads to 9-cis reaction is limited to extremely low efficiency. At liquid nitrogen temperature, 11 cis in equilibrium all-trans in equilibrium 9-cis reaction takes place. At intermediary low temperatures (-80 degrees C to -15 degrees C) another isomer of retinal may be produced by the irradiation, which forms a pigment having an absorbance maximum at 465 nm (P-465). The formation of P-465 decreases remarkably in the narrow temperature range from -30 degrees C to 0 degrees C where mesorhodopsin converts to metarhodopsin. Medsorhodopsin is quite different from metarhodopsin in the photoisomerization of the chromophore because P-465 is produced from the former but not from the latter. No P-465 is produced both at liquid nitrogen temperature and above 0 degrees C. P-465 is more labile than any of the other photoproducts so far known, that is isorhodopsin, alkaline and acid metarhodopsins. P-465 is converted to metarhodopsin by irradiation.", "contents": "Studies on cephalopod rhodopsin: photoisomerization of the chromophore. Photoisomerization of the chromophore of squid rhodopsin is dependent upon the irradiation temperature. Above 0 degrees C, only 11-cis in equilibrium all-trans reaction proceeds and the all-trans leads to 9-cis reaction is limited to extremely low efficiency. At liquid nitrogen temperature, 11 cis in equilibrium all-trans in equilibrium 9-cis reaction takes place. At intermediary low temperatures (-80 degrees C to -15 degrees C) another isomer of retinal may be produced by the irradiation, which forms a pigment having an absorbance maximum at 465 nm (P-465). The formation of P-465 decreases remarkably in the narrow temperature range from -30 degrees C to 0 degrees C where mesorhodopsin converts to metarhodopsin. Medsorhodopsin is quite different from metarhodopsin in the photoisomerization of the chromophore because P-465 is produced from the former but not from the latter. No P-465 is produced both at liquid nitrogen temperature and above 0 degrees C. P-465 is more labile than any of the other photoproducts so far known, that is isorhodopsin, alkaline and acid metarhodopsins. P-465 is converted to metarhodopsin by irradiation."} {"id": "PMID:1276164", "title": "Metabolic aspects of the secretion of stored compounds from blood platelets. IV. Effects of ionophore X537A on washed platelets.", "content": "1. X537A at concentrations below 10 muM can liberate platelet serotonin from washed human platelets without inducing the platelet release reaction. Up to 100% of serotonin preabsorbed by the platelets can be liberated before initiation of the release reaction. 2. Concentrations of X537A above 10muM initiate the platelet release reaction, with a maximum release of adenine nucleotides and platelet factor 4 antigen comparable to that obtained with 1.25 units thrombin/ml. 3. The changes in ATP metabolism at the concentration necessary for X537A-induced release are more profound than those in platelets exposed to concentrations of thrombin or A23187 giving the same degree of release, and approach those seen with high concentrations of A23187. At concentrations where serotonin is liberated but no adenine nucleotide or platelet factor 4 antigen is released, short time incubation causes no change in the level of metabolic ATP.", "contents": "Metabolic aspects of the secretion of stored compounds from blood platelets. IV. Effects of ionophore X537A on washed platelets. 1. X537A at concentrations below 10 muM can liberate platelet serotonin from washed human platelets without inducing the platelet release reaction. Up to 100% of serotonin preabsorbed by the platelets can be liberated before initiation of the release reaction. 2. Concentrations of X537A above 10muM initiate the platelet release reaction, with a maximum release of adenine nucleotides and platelet factor 4 antigen comparable to that obtained with 1.25 units thrombin/ml. 3. The changes in ATP metabolism at the concentration necessary for X537A-induced release are more profound than those in platelets exposed to concentrations of thrombin or A23187 giving the same degree of release, and approach those seen with high concentrations of A23187. At concentrations where serotonin is liberated but no adenine nucleotide or platelet factor 4 antigen is released, short time incubation causes no change in the level of metabolic ATP."} {"id": "PMID:1276165", "title": "Antivitamin B-6 effect of 1-aminoproline on rats.", "content": "By intraperitoneal injection of 1-aminoproline, death after severe convulsion was observed in rats (LD50 of 1-amino-L-proline, 26 mg per kg of body weight for young male rats fed a normal diet). The vitamin B-6-deficient rats were more sensitive to this hydrazino acid than the normal rats. The toxic effect was completely prevented by the administration of pyridoxine. 1-Amino-D-proline was less toxic than the L-isomer. By the 1-aminoproline treatment, the most remarkable changes in the free amino acid levels were the striking increases in the concentrations of alpha-aminoadipic acid, citrulline and cystathionine in all the tissues tested, except in brain. Some unidentified ninhydrin-positive substances appeared. These results indicate that 1-aminoproline greatly disturbed the amino acid pattern, i.e. the amino acid metabolism in rats.", "contents": "Antivitamin B-6 effect of 1-aminoproline on rats. By intraperitoneal injection of 1-aminoproline, death after severe convulsion was observed in rats (LD50 of 1-amino-L-proline, 26 mg per kg of body weight for young male rats fed a normal diet). The vitamin B-6-deficient rats were more sensitive to this hydrazino acid than the normal rats. The toxic effect was completely prevented by the administration of pyridoxine. 1-Amino-D-proline was less toxic than the L-isomer. By the 1-aminoproline treatment, the most remarkable changes in the free amino acid levels were the striking increases in the concentrations of alpha-aminoadipic acid, citrulline and cystathionine in all the tissues tested, except in brain. Some unidentified ninhydrin-positive substances appeared. These results indicate that 1-aminoproline greatly disturbed the amino acid pattern, i.e. the amino acid metabolism in rats."} {"id": "PMID:1276166", "title": "The murine sublingual and submandibular mucins. Their isolation and characterization.", "content": "From the mouse sublingual and submandibular glands high-molecular weight glycoproteins (mucins) were isolated. These mucins appeared to be homogeneous in polyacrylamide gel electrophoresis and in the analytical ultracentrifuge. S20,W values of 10.9 and 5.5 were found for the sublingual and submandibular mucin respectively. With sodium dodecyl sulfate or N-acetylcysteine no subunits could be detected. Both mucins consisted for about 1/3 of protein and 2/3 carbohydrate. Their mucin character was also denoted by the high content of serine plus threonine. Respectively 42 mol% and 34 mol% of the protein core of the sublingual and submandibular mucins consisted of these amino acids. The main sugars in these mucins were sialic acid, galactosamine, galactose, glucosamine and mannose. The molar ratio for the sublingual and submandibular mucin being 1.00 : 1.03 : 1.08 : 0.26 : 0.23 and 1.00 : 0.71 : 1.10 : 0.65 : 0.53, respectively. The sialic acid content of both mucins was about 25%. Fucose and sulfate, on the other hand, were less than 1%. The presence of sulfate was also indicated by preliminary studies in vivo on the incorporation of [35SO4] sulfate.", "contents": "The murine sublingual and submandibular mucins. Their isolation and characterization. From the mouse sublingual and submandibular glands high-molecular weight glycoproteins (mucins) were isolated. These mucins appeared to be homogeneous in polyacrylamide gel electrophoresis and in the analytical ultracentrifuge. S20,W values of 10.9 and 5.5 were found for the sublingual and submandibular mucin respectively. With sodium dodecyl sulfate or N-acetylcysteine no subunits could be detected. Both mucins consisted for about 1/3 of protein and 2/3 carbohydrate. Their mucin character was also denoted by the high content of serine plus threonine. Respectively 42 mol% and 34 mol% of the protein core of the sublingual and submandibular mucins consisted of these amino acids. The main sugars in these mucins were sialic acid, galactosamine, galactose, glucosamine and mannose. The molar ratio for the sublingual and submandibular mucin being 1.00 : 1.03 : 1.08 : 0.26 : 0.23 and 1.00 : 0.71 : 1.10 : 0.65 : 0.53, respectively. The sialic acid content of both mucins was about 25%. Fucose and sulfate, on the other hand, were less than 1%. The presence of sulfate was also indicated by preliminary studies in vivo on the incorporation of [35SO4] sulfate."} {"id": "PMID:1276167", "title": "Physical studies on glycoproteins from ascitic fluid of Ehrlich ascites tumor.", "content": "Three glycoproteins, designated as F, M and S glycoproteins were identified in the HCIO4-soluble fraction of ascitic fluid of Ehrlich ascites tumor by 8% polyacrylamide disc gel electrophoresis. They were separated and purified as described previously (Reznick, A.Z. and Winzler, R.J. (1973) Fed. Proc. 32, 368 and Reznick, A.Z., Allen, H.J. and Winzler, R.J. (1973) Anal. Biochem. 52, 395-401) and subjected to physical characterization. Several physical properties such as molecular weights, sedimentation and diffusion coefficients, partial specific volumes, Stoke's radii and frictional ratios were determined. The physical parameters of F and S glycoproteins resemble data that have been reported for orosomucoid and haptoglobin-like glycoproteins, respectively. Properties of M glycoprotein could not be associated with a known glycoprotein.", "contents": "Physical studies on glycoproteins from ascitic fluid of Ehrlich ascites tumor. Three glycoproteins, designated as F, M and S glycoproteins were identified in the HCIO4-soluble fraction of ascitic fluid of Ehrlich ascites tumor by 8% polyacrylamide disc gel electrophoresis. They were separated and purified as described previously (Reznick, A.Z. and Winzler, R.J. (1973) Fed. Proc. 32, 368 and Reznick, A.Z., Allen, H.J. and Winzler, R.J. (1973) Anal. Biochem. 52, 395-401) and subjected to physical characterization. Several physical properties such as molecular weights, sedimentation and diffusion coefficients, partial specific volumes, Stoke's radii and frictional ratios were determined. The physical parameters of F and S glycoproteins resemble data that have been reported for orosomucoid and haptoglobin-like glycoproteins, respectively. Properties of M glycoprotein could not be associated with a known glycoprotein."} {"id": "PMID:1276168", "title": "Evidence for mannolipids as intermediates in mannose transfer to thyroid rough microsomal glycoproteins.", "content": "Thyroid rough microsomes catalyzed the transfer of mannose from GDP-mannose to endogeneous glycoprotein(s) and to glycolipids comprising a recently described dolichol phosphomannose extractable with usual organic solvents and a material tentatively identified as an oligosaccharide lipid. The labeling of the two lipids was consistent with a role in mannose transfer to glycoprotein(s). When partially purified dolichol phospho[14C] mannose was incubated with rough microsomes, a part of the label appeared in the second lipid, suggesting a role as intermediate, and less rapidly in glycoprotein(s). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis did not allow to ascertain whether or not the glycoproteins receiving label from these sugar lipids comprised thyroglobulin precursors.", "contents": "Evidence for mannolipids as intermediates in mannose transfer to thyroid rough microsomal glycoproteins. Thyroid rough microsomes catalyzed the transfer of mannose from GDP-mannose to endogeneous glycoprotein(s) and to glycolipids comprising a recently described dolichol phosphomannose extractable with usual organic solvents and a material tentatively identified as an oligosaccharide lipid. The labeling of the two lipids was consistent with a role in mannose transfer to glycoprotein(s). When partially purified dolichol phospho[14C] mannose was incubated with rough microsomes, a part of the label appeared in the second lipid, suggesting a role as intermediate, and less rapidly in glycoprotein(s). Sodium dodecyl sulfate/polyacrylamide gel electrophoresis did not allow to ascertain whether or not the glycoproteins receiving label from these sugar lipids comprised thyroglobulin precursors."} {"id": "PMID:1276169", "title": "Early labeled heme synthesis in normal rats and rats with iron deficiency anemia.", "content": "Heme synthesis from [2-14C]glycine was studied in liver and red blood cells. In normal rats liver contained two early [14C] heme peaks maximal at 1 and 4.5 h, followed by a long plateau of heme labeling. These phases were present in both microsomes and mitochondria. Cycloheximide suppressed formation of the first but not the second heme component. All phases of hepatic heme labeling were reduced in iron-deficient rats, with better preservation ofthe microsomal fraction. In iron-deficient rats responding to iron therapy, the first peak merged with an enlarged and premature second component; the increase was most marked in mitochondria. Thus, labeled heme metabolism was less perturbed in microsomes than mitochondria in both of these conditions. Peripheral blood also contained a [14C] heme peak at 1 h in all experimental groups. This was highest with the increased eythroid response observed in iron-treated rats. The first heme peak, present in both hepatic and erythroid cells, may represent a pool of free or unassigned heme. The later heme component may reflect formation of hemoproteins, which could be related directly or in directly to the initial, rapid turnover heme component.", "contents": "Early labeled heme synthesis in normal rats and rats with iron deficiency anemia. Heme synthesis from [2-14C]glycine was studied in liver and red blood cells. In normal rats liver contained two early [14C] heme peaks maximal at 1 and 4.5 h, followed by a long plateau of heme labeling. These phases were present in both microsomes and mitochondria. Cycloheximide suppressed formation of the first but not the second heme component. All phases of hepatic heme labeling were reduced in iron-deficient rats, with better preservation ofthe microsomal fraction. In iron-deficient rats responding to iron therapy, the first peak merged with an enlarged and premature second component; the increase was most marked in mitochondria. Thus, labeled heme metabolism was less perturbed in microsomes than mitochondria in both of these conditions. Peripheral blood also contained a [14C] heme peak at 1 h in all experimental groups. This was highest with the increased eythroid response observed in iron-treated rats. The first heme peak, present in both hepatic and erythroid cells, may represent a pool of free or unassigned heme. The later heme component may reflect formation of hemoproteins, which could be related directly or in directly to the initial, rapid turnover heme component."} {"id": "PMID:1276170", "title": "Alterations of mitochondrial protein metabolism in liver, brown adipose tissue and skeletal muscle. During cold-acclimation.", "content": "Incorporation of L-[U-14C] leucine into liver, brown adipose tissue and skeletal muscle mitochondrial proteins was determined in vivo and in vitro during cold-acclimation. Major alterations in mitochondrial protein metabolism were observed in brown adipose tissue and skeletal muscle but not in liver. Immediate cold-exposure is accompanied by an inhibition of the in vivo incorporation of L-[U-14C] leucine into mitochondrial proteins of all tissues. However, during cold-acclimation the incorporation of leucine increases markedly in brown adipose tissue, continues to decrease in skeletal muscle, nut does not change appreciably in the liver. Because increased incorporation of L-[U-14C]-leucine into brown adipose tissue mitochondrial proteins was observed both in vivo and in vitro, it can be concluded that the mitochondrial protein-synthesizing system of this tissue is directly affected by the acclimation process. The observed changes in mitochondrial protein metabolism of brown adipose tissue and skeletal muscle might be responsible for the development of several morphological and biochemical alterations that characterize the establishment in these tissues of the cold-acclimated state.", "contents": "Alterations of mitochondrial protein metabolism in liver, brown adipose tissue and skeletal muscle. During cold-acclimation. Incorporation of L-[U-14C] leucine into liver, brown adipose tissue and skeletal muscle mitochondrial proteins was determined in vivo and in vitro during cold-acclimation. Major alterations in mitochondrial protein metabolism were observed in brown adipose tissue and skeletal muscle but not in liver. Immediate cold-exposure is accompanied by an inhibition of the in vivo incorporation of L-[U-14C] leucine into mitochondrial proteins of all tissues. However, during cold-acclimation the incorporation of leucine increases markedly in brown adipose tissue, continues to decrease in skeletal muscle, nut does not change appreciably in the liver. Because increased incorporation of L-[U-14C]-leucine into brown adipose tissue mitochondrial proteins was observed both in vivo and in vitro, it can be concluded that the mitochondrial protein-synthesizing system of this tissue is directly affected by the acclimation process. The observed changes in mitochondrial protein metabolism of brown adipose tissue and skeletal muscle might be responsible for the development of several morphological and biochemical alterations that characterize the establishment in these tissues of the cold-acclimated state."} {"id": "PMID:1276171", "title": "Enzymes of ornithine metabolism in adult and developing rat intestine.", "content": "The levels of 11 enzymes, most of them involved in the metabolism of ornithine, were measured in whole upper intestine, or in duodenum, small intestine and colon of adult rats. The developmental formations in small intestine of arginase, ornithine aminotransferase, and ornithine transcarbamylase were compared with those in liver. Changes with age (late gestation of adult) of the intestinal activities of pyrroline-5-carboxylate reductase, proline oxidase and glutamyl transpeptidase are also described. The results suggest that the proximal part of the intestine is well endowed with enzymes involved in the conversion of ornithine to proline as well as to citrulline. Fetal intestine is rich in proline oxidase and pyrroline-5-carboxylate reductase. The peak levels of ornithine aminotransferase found in intestine in the first 3 postnatal weeks were higher than seen in any other rat tissue. Some of the properties of arginase, ornithine aminotransferase and pyrroline-5-carboxylate reductase in small intestine were compared with those in liver. Isozymes of arginase in small intestine differed from those in liver; the kinetic properties of ornithine aminotransferase were similar in the two tissues. In intestine of 14-day-old rats, the ornithine aminotransferase reaction was reversible, forming ornithine from pyrroline-5-carboxylate. The intestinal pyrroline-5-carboxylate reductase was cold-labile as was the hepatic enzyme in rat.", "contents": "Enzymes of ornithine metabolism in adult and developing rat intestine. The levels of 11 enzymes, most of them involved in the metabolism of ornithine, were measured in whole upper intestine, or in duodenum, small intestine and colon of adult rats. The developmental formations in small intestine of arginase, ornithine aminotransferase, and ornithine transcarbamylase were compared with those in liver. Changes with age (late gestation of adult) of the intestinal activities of pyrroline-5-carboxylate reductase, proline oxidase and glutamyl transpeptidase are also described. The results suggest that the proximal part of the intestine is well endowed with enzymes involved in the conversion of ornithine to proline as well as to citrulline. Fetal intestine is rich in proline oxidase and pyrroline-5-carboxylate reductase. The peak levels of ornithine aminotransferase found in intestine in the first 3 postnatal weeks were higher than seen in any other rat tissue. Some of the properties of arginase, ornithine aminotransferase and pyrroline-5-carboxylate reductase in small intestine were compared with those in liver. Isozymes of arginase in small intestine differed from those in liver; the kinetic properties of ornithine aminotransferase were similar in the two tissues. In intestine of 14-day-old rats, the ornithine aminotransferase reaction was reversible, forming ornithine from pyrroline-5-carboxylate. The intestinal pyrroline-5-carboxylate reductase was cold-labile as was the hepatic enzyme in rat."} {"id": "PMID:1276172", "title": "The effect of ethanol ingestion on the aldehyde dehydrogenases of rat liver.", "content": "The effect of ethanol ingestion on aldehyde dehydrogenase activity in the subcellular fractions of livers from 14 pair-fed male Sprague-Dawley rats was tested. Enzymatic assays were performed at two different concentrations of propionaldehyde (0.068 and 13.6 mM) sufficient to saturate enzymes with high and low affinities for propionaldehyde, respectively. The effect of alcohol ingestion varied depending on the subcellular fraction tested and the propionaldehyde concentration used in the assay. There was a 60% increase in the activity of aldehyde dehydrogenase with high affinity for propionaldehyde in the mitochondrial membranes. Conversely there was a 50% decrease in the activity of aldehyde dehydrogenases with high affinity for propionaldehyde in the microsomal fraction. There was also a 58% decrease in the activity of enzymes from the mitochondrial matrix with low affinity for propionaldehyde. The results suggest that differences in the assay systems employed may account for the conflicting results obtained by previous investigators of the effect of ethanol feeding.", "contents": "The effect of ethanol ingestion on the aldehyde dehydrogenases of rat liver. The effect of ethanol ingestion on aldehyde dehydrogenase activity in the subcellular fractions of livers from 14 pair-fed male Sprague-Dawley rats was tested. Enzymatic assays were performed at two different concentrations of propionaldehyde (0.068 and 13.6 mM) sufficient to saturate enzymes with high and low affinities for propionaldehyde, respectively. The effect of alcohol ingestion varied depending on the subcellular fraction tested and the propionaldehyde concentration used in the assay. There was a 60% increase in the activity of aldehyde dehydrogenase with high affinity for propionaldehyde in the mitochondrial membranes. Conversely there was a 50% decrease in the activity of aldehyde dehydrogenases with high affinity for propionaldehyde in the microsomal fraction. There was also a 58% decrease in the activity of enzymes from the mitochondrial matrix with low affinity for propionaldehyde. The results suggest that differences in the assay systems employed may account for the conflicting results obtained by previous investigators of the effect of ethanol feeding."} {"id": "PMID:1276173", "title": "Effect of estradiol and progesterone on UDPgalactose pyrophosphatase activity in the endometrium of ovariectomized rats.", "content": "Rat endometrium was found to contain a UDPgalactose pyrophosphatase for the hydrolysis of UDPgalactose into galactose 1-phosphate and UMP. The adminstration of 17beta-estradiol to ovariectomized rats resulted in a significant decrease in the activity of the enzyme in endometrium while have little effect on that in myometrium. The response was linear with the dose of estradiol and as little as 0.07 mug per 100 g body weight produced maximum inhibition of the enzyme. Progesterone on its own had little effect on the enzyme activity but in combination with estradiol, it effectively prevented the inhibitory effect of estradiol. This inhibitory effect of estradiol on the activity of UDPgalactose pyrophosphatase may function in the regulation of glycoprotein biosynthesis in endometrium.", "contents": "Effect of estradiol and progesterone on UDPgalactose pyrophosphatase activity in the endometrium of ovariectomized rats. Rat endometrium was found to contain a UDPgalactose pyrophosphatase for the hydrolysis of UDPgalactose into galactose 1-phosphate and UMP. The adminstration of 17beta-estradiol to ovariectomized rats resulted in a significant decrease in the activity of the enzyme in endometrium while have little effect on that in myometrium. The response was linear with the dose of estradiol and as little as 0.07 mug per 100 g body weight produced maximum inhibition of the enzyme. Progesterone on its own had little effect on the enzyme activity but in combination with estradiol, it effectively prevented the inhibitory effect of estradiol. This inhibitory effect of estradiol on the activity of UDPgalactose pyrophosphatase may function in the regulation of glycoprotein biosynthesis in endometrium."} {"id": "PMID:1276174", "title": "Haem-binding proteins of the rat liver cytosol.", "content": "Gel filtration of soluble supernatant fraction obtained from livers of rats 10 min after an injection of the haem precursor 5-amino[3H]laevulinic acid shows the presence of a major radioactive fraction which upon gel filtration is similar in elution volume to ligandin. 20 min after administration of the precursor four previously minor components also come into prominence. This pattern is a characteristic of in vivo binding since a different elution pattern is obtained if soluble supernatant fraction from rat liver is labelled in vitro by incubation either with [3H]haem-labelled mitochondria, [3H]haem-labelled microsomes or with [3H]haemin. These results are discussed with particular reference to ligandin.", "contents": "Haem-binding proteins of the rat liver cytosol. Gel filtration of soluble supernatant fraction obtained from livers of rats 10 min after an injection of the haem precursor 5-amino[3H]laevulinic acid shows the presence of a major radioactive fraction which upon gel filtration is similar in elution volume to ligandin. 20 min after administration of the precursor four previously minor components also come into prominence. This pattern is a characteristic of in vivo binding since a different elution pattern is obtained if soluble supernatant fraction from rat liver is labelled in vitro by incubation either with [3H]haem-labelled mitochondria, [3H]haem-labelled microsomes or with [3H]haemin. These results are discussed with particular reference to ligandin."} {"id": "PMID:1276175", "title": "Effect of clofibrate treatment on carnitine acyltransferases in different subcellular fractions of rat liver.", "content": "The subcellular distribution of carnitine acetyl-, octanoyl-, and palmitoyl- transferase in the livers of normal and clofibrate-treated male rats was studied with isopycnic sucrose density gradient fractionation. In normal liver 48% of total carnitine acetyltransferase activity was peroxisomal, 36% of the activity located in mitochondria and 16% in a membranous fraction containing microsomes. Carnitine octanoyltransferase and carnitine palmitoyltransferase were confined almost totally (77--81%) to mitochondria in normal liver. Clofibrate treatment increased the total activity of carnitine acetyltransferase over 30 times, whereas the total activities of the other two transferases were increased only 5-fold. From the three different subcellular carnitine acetyltransferases the mitochondrial one was most responsive to clofibrate treatment, i.e. the rise in mitochondrial activity was over 70-fold as contrasted to the 6- and 14-fold rises in peroxisomal and microsomal activities, respectively. After treatment mitochondria contained 79% of total activity. It is concluded that the clofibrate-induced increase of carnitine acetyltransferase activity is not due to the peroxisomal proliferation that occurs during clofibrate treatment. The rise in peroxisomal activity contributed only 8% to the total increase. After clofibrate treatment the greatest part of carnitine octanoyl- and palmitoyltransferase activities were located in mitochondria but a considerable amount of both activities was found also in the soluble fraction of liver.", "contents": "Effect of clofibrate treatment on carnitine acyltransferases in different subcellular fractions of rat liver. The subcellular distribution of carnitine acetyl-, octanoyl-, and palmitoyl- transferase in the livers of normal and clofibrate-treated male rats was studied with isopycnic sucrose density gradient fractionation. In normal liver 48% of total carnitine acetyltransferase activity was peroxisomal, 36% of the activity located in mitochondria and 16% in a membranous fraction containing microsomes. Carnitine octanoyltransferase and carnitine palmitoyltransferase were confined almost totally (77--81%) to mitochondria in normal liver. Clofibrate treatment increased the total activity of carnitine acetyltransferase over 30 times, whereas the total activities of the other two transferases were increased only 5-fold. From the three different subcellular carnitine acetyltransferases the mitochondrial one was most responsive to clofibrate treatment, i.e. the rise in mitochondrial activity was over 70-fold as contrasted to the 6- and 14-fold rises in peroxisomal and microsomal activities, respectively. After treatment mitochondria contained 79% of total activity. It is concluded that the clofibrate-induced increase of carnitine acetyltransferase activity is not due to the peroxisomal proliferation that occurs during clofibrate treatment. The rise in peroxisomal activity contributed only 8% to the total increase. After clofibrate treatment the greatest part of carnitine octanoyl- and palmitoyltransferase activities were located in mitochondria but a considerable amount of both activities was found also in the soluble fraction of liver."} {"id": "PMID:1276176", "title": "Effect of triamcinolone administration on content of flavins in rabbit liver.", "content": "Triamcinoline acetonide (10 mg per kg of body weight a day) was administered to rabbit fed on a laboratory chow diet. The content of flavins in liver but not in kidney, muscle and brain started to decrease 24 h after a single dose. The activities of enzymes in the liver were determined: the activities of pyruvate dehydrogenase complex, lipoamide dehydrogenase (NADH:lipoamide oxidoreductase EC 1.6.4.3), NADH dehydrogenase (NADH : (acceptor) oxidoreductase EC 1.6.99.3) and D-amino acid oxidase (D-amino acid: oxygen oxidoreductase (deaminating) EC 1.4.3.3) were decreased but those of succinate dehydrogenase (succinate : (acceptor) oxidoreductase EC 1.3.99.1) and xanthine oxidase (xanthine : oxygen oxidoreductase EC 1.2.3.2) remained unchanged. The activities of enzymes in the kidney, however, remained unchanged except the decrease in the activity of pyruvate dehydrogenase complex.", "contents": "Effect of triamcinolone administration on content of flavins in rabbit liver. Triamcinoline acetonide (10 mg per kg of body weight a day) was administered to rabbit fed on a laboratory chow diet. The content of flavins in liver but not in kidney, muscle and brain started to decrease 24 h after a single dose. The activities of enzymes in the liver were determined: the activities of pyruvate dehydrogenase complex, lipoamide dehydrogenase (NADH:lipoamide oxidoreductase EC 1.6.4.3), NADH dehydrogenase (NADH : (acceptor) oxidoreductase EC 1.6.99.3) and D-amino acid oxidase (D-amino acid: oxygen oxidoreductase (deaminating) EC 1.4.3.3) were decreased but those of succinate dehydrogenase (succinate : (acceptor) oxidoreductase EC 1.3.99.1) and xanthine oxidase (xanthine : oxygen oxidoreductase EC 1.2.3.2) remained unchanged. The activities of enzymes in the kidney, however, remained unchanged except the decrease in the activity of pyruvate dehydrogenase complex."} {"id": "PMID:1276177", "title": "Protein-lipid interactions in the sialic acid incorporating system of liver microsomes.", "content": "The conditions for the incorporation of sialic acid (N-acetylneuraminic acid) from CMP-sialic acid into endogenous acceptors of rat liver microsomes has been studied. It is shown that the incorporating activity can be solubilized by extraction of the microsomes with a mild detergent, Triton X-100. The specific activity of the soluble system is about sixfold compared to the original microsomes. Removal of lipids from the system greatly reduces its ability to incorporate sialic acid. Recombination with phospholipids prepared from liver microsomes restores the activity. Other lipids are ineffective, and single phospholipid fractions are less effective than the phospholipid mixture. It is concluded that the system studied, comprising both sialyl transferase and sialyl acceptor-protein is a typical intrinsic membrane protein system, dependent on a hydrophobic environment for full activity.", "contents": "Protein-lipid interactions in the sialic acid incorporating system of liver microsomes. The conditions for the incorporation of sialic acid (N-acetylneuraminic acid) from CMP-sialic acid into endogenous acceptors of rat liver microsomes has been studied. It is shown that the incorporating activity can be solubilized by extraction of the microsomes with a mild detergent, Triton X-100. The specific activity of the soluble system is about sixfold compared to the original microsomes. Removal of lipids from the system greatly reduces its ability to incorporate sialic acid. Recombination with phospholipids prepared from liver microsomes restores the activity. Other lipids are ineffective, and single phospholipid fractions are less effective than the phospholipid mixture. It is concluded that the system studied, comprising both sialyl transferase and sialyl acceptor-protein is a typical intrinsic membrane protein system, dependent on a hydrophobic environment for full activity."} {"id": "PMID:1276178", "title": "The distribution of serum albumin in human normal and degenerate articular cartilage.", "content": "A method for studying the distribution of a high molecular weight solute (serum albumin) between physiological saline and human articular cartilage is described. Samples of normal and fibrillated articular cartilage from both femoral condyles and femoral heads have been studied. Limited studies have also been performed where the glycosaminoglycan content of normal cartilage has been reduced by chemical or enzymic methods. With naturally occurring cartilage a wide range of partition coefficients (0.3 to less than 0.002) was obtained. The partition coefficients are very dependent upon proteoglycan concentration, with the partition coefficient decreasing with increasing fixed charge density. An attempt is made to interpret the observed partitioning in terms of the steric exclusion by the proteoglycans.", "contents": "The distribution of serum albumin in human normal and degenerate articular cartilage. A method for studying the distribution of a high molecular weight solute (serum albumin) between physiological saline and human articular cartilage is described. Samples of normal and fibrillated articular cartilage from both femoral condyles and femoral heads have been studied. Limited studies have also been performed where the glycosaminoglycan content of normal cartilage has been reduced by chemical or enzymic methods. With naturally occurring cartilage a wide range of partition coefficients (0.3 to less than 0.002) was obtained. The partition coefficients are very dependent upon proteoglycan concentration, with the partition coefficient decreasing with increasing fixed charge density. An attempt is made to interpret the observed partitioning in terms of the steric exclusion by the proteoglycans."} {"id": "PMID:1276179", "title": "The effects of proteolytic enzymes on the mechanical properties of adult human articular cartilage.", "content": "The effects of the lysosomal proteinase cathepsin D on the mechanical properties of adult human articular cartilage were examined in detail in 7 joints within the age range 21 to 72 years. The results of a preliminary study on the effects of the lysosomal proteinase cathepsin B1 and clostridial collagenase on the mechanical properties of cartilage are also presented. Cartilage which had been incubated with either cathepsin D or cathepsin B1 showed increased deformation in uniaxial compression perpendicular to the articular surface. The enzyme-treated cartilage also showed decreased tensile stiffness at low values of stress. This effect was more pronounced in specimens from the deeper zone of cartilage than in specimens from the superficial zone. It was also more pronounced in specimens which were aligned perpendicular to the predominant alignment of the collagen fibres in the superficial zone than in specimens which were parallel to the collagen fibres. At higher stresses the tensile stiffness of the treated cartilage was not significantly different from that of the untreated tissue. The tensile fracture stress of the cartilage was also not significantly reduced by the action of cathepsin D. In contrast to the effects observed with the cathepsins, the preliminary results obtained by incubating cartilage for 24 h with clostridial collagenase showed that both the tensile stiffness and the fracture stress were considerably lower than the corresponding values for the untreated tissue. Biochemical analysis of the incubation media, and the specimens, revealed that a large proportion of the proteoglycans was released from the cartilage by each of the three enzymes. The proportion of the total collagen which was released from the cartilage was different for each enzyme: cathepsin D released between 0 and 1.5 per cent, cathepsin B1 released between 2.3 and 4.3 per cent and collagenase released between 5.3 and 27.8 per cent of the collagen after 24 h.", "contents": "The effects of proteolytic enzymes on the mechanical properties of adult human articular cartilage. The effects of the lysosomal proteinase cathepsin D on the mechanical properties of adult human articular cartilage were examined in detail in 7 joints within the age range 21 to 72 years. The results of a preliminary study on the effects of the lysosomal proteinase cathepsin B1 and clostridial collagenase on the mechanical properties of cartilage are also presented. Cartilage which had been incubated with either cathepsin D or cathepsin B1 showed increased deformation in uniaxial compression perpendicular to the articular surface. The enzyme-treated cartilage also showed decreased tensile stiffness at low values of stress. This effect was more pronounced in specimens from the deeper zone of cartilage than in specimens from the superficial zone. It was also more pronounced in specimens which were aligned perpendicular to the predominant alignment of the collagen fibres in the superficial zone than in specimens which were parallel to the collagen fibres. At higher stresses the tensile stiffness of the treated cartilage was not significantly different from that of the untreated tissue. The tensile fracture stress of the cartilage was also not significantly reduced by the action of cathepsin D. In contrast to the effects observed with the cathepsins, the preliminary results obtained by incubating cartilage for 24 h with clostridial collagenase showed that both the tensile stiffness and the fracture stress were considerably lower than the corresponding values for the untreated tissue. Biochemical analysis of the incubation media, and the specimens, revealed that a large proportion of the proteoglycans was released from the cartilage by each of the three enzymes. The proportion of the total collagen which was released from the cartilage was different for each enzyme: cathepsin D released between 0 and 1.5 per cent, cathepsin B1 released between 2.3 and 4.3 per cent and collagenase released between 5.3 and 27.8 per cent of the collagen after 24 h."} {"id": "PMID:1276180", "title": "Refractoriness of ovarian adenylate cyclase to continued hormonal stimulation.", "content": "Culture of preovulatory rat follicles with luteinizing hormone, follicle-stimulating hormone or prostaglandin E2 for 24 h reduced the subsequent response of adenylate cyclase to the homologous by 80, 50 and 90%, respectively; yet follicles refractory to luteinizing hormone fully responded to follicle-stimulating hormone responded to luteinizing hormone and prostaglandin E2, and those refractory to prostaglandin E2 could be stimulated by either gonadotropin. Desensitization of the adenylate cyclase system by luteinizing hormone was achieved by hormone concentrations of 0.8--2.0 mug/ml in the medium; a lower dose of luteinizing hormone (0.4 mug/ml), though effective in stimulating adenylate cyclase, did not induce refractoriness. Prostaglandin E2 caused partial refractoriness at dose levels of 0.1--0.25 mug/ml; higher dose levels were more effective. These findings suggest that continued exposure to the preovulatory follicle to elevated levels of hormones may cause perturbations in either the interaction between the hormone and its specific receptor or in a subsequent step essential for activation of adenylate cyclase.", "contents": "Refractoriness of ovarian adenylate cyclase to continued hormonal stimulation. Culture of preovulatory rat follicles with luteinizing hormone, follicle-stimulating hormone or prostaglandin E2 for 24 h reduced the subsequent response of adenylate cyclase to the homologous by 80, 50 and 90%, respectively; yet follicles refractory to luteinizing hormone fully responded to follicle-stimulating hormone responded to luteinizing hormone and prostaglandin E2, and those refractory to prostaglandin E2 could be stimulated by either gonadotropin. Desensitization of the adenylate cyclase system by luteinizing hormone was achieved by hormone concentrations of 0.8--2.0 mug/ml in the medium; a lower dose of luteinizing hormone (0.4 mug/ml), though effective in stimulating adenylate cyclase, did not induce refractoriness. Prostaglandin E2 caused partial refractoriness at dose levels of 0.1--0.25 mug/ml; higher dose levels were more effective. These findings suggest that continued exposure to the preovulatory follicle to elevated levels of hormones may cause perturbations in either the interaction between the hormone and its specific receptor or in a subsequent step essential for activation of adenylate cyclase."} {"id": "PMID:1276181", "title": "Drop weight variation in an automated collection procedure and its relationship to apparent surface tension.", "content": "A drop counter-regulated fraction collector yields samples containing equal numbers of drops. Such fractions vary slightly in weight depending on experimental conditions such as surface tension. Provided that variables such as flow rate and eluate density remain constant, apparent surface tension may be estimated directly from the weights of eluate fractions obtained from gel filtration experiments. The detergents sodium cholate and sodium lauryl sulphate significantly decreased drop weights in this system. Following gel filtration on Sepharose 4B, sodium cholate eluted in the fractions containing low molecular weight material. It eluted in the same position when pre-mixed with human plasma. Normal plasma was found to contain two surface tension-reducing components with apparent molecular weights of 3-10(6) and 1-10(5). The apparent surface tension of whole human plasma was found to be time dependent and decreased as the flow rate was reduced.", "contents": "Drop weight variation in an automated collection procedure and its relationship to apparent surface tension. A drop counter-regulated fraction collector yields samples containing equal numbers of drops. Such fractions vary slightly in weight depending on experimental conditions such as surface tension. Provided that variables such as flow rate and eluate density remain constant, apparent surface tension may be estimated directly from the weights of eluate fractions obtained from gel filtration experiments. The detergents sodium cholate and sodium lauryl sulphate significantly decreased drop weights in this system. Following gel filtration on Sepharose 4B, sodium cholate eluted in the fractions containing low molecular weight material. It eluted in the same position when pre-mixed with human plasma. Normal plasma was found to contain two surface tension-reducing components with apparent molecular weights of 3-10(6) and 1-10(5). The apparent surface tension of whole human plasma was found to be time dependent and decreased as the flow rate was reduced."} {"id": "PMID:1276182", "title": "Functional consequences of ligand-linked dissociation in hemoglobin from the sea cucumber Molpadia arenicola.", "content": "It has been established that Molpadia hemoglobin tends to dissociate into subunits as oxygen is bound. The kinetics and equilibria of carbon monoxide and ethylisocyanide binding reported here show a dependence on protein concentration that supports the conclusion that the aggregated hemoglobin has a lower ligand affinity than the dissociated subunits. This is true for the isolated D-chain as well as for the unfractionated hemolysate that contains four distinct polypeptide chains (A-D). This indicates that even homopolymers of Molpadia hemoglobin have lower ligand affinity than the dissociated subunits. At high protein concentration hemolysates of Molpadia hemoglobin show slight cooperativity. The time course of ligand binding to the deoxy D-chain also suggests cooperative interactions. The low affinity of the aggregated state may have a different molecular explanation than in human hemoglobin where tetramers of identical subunits (as in Hb H) show high oxygen affinity. The absence of tyrosine and histidine at the C-terminal of the Molpadia D-chains also suggests a different stabilization of the low affinity deoxy state. An additional functional difference between Molpadia hemoglobin and human hemoglobin is that organic phosphates do not alter the ligand affinity of the sea cucumber hemoglobin.", "contents": "Functional consequences of ligand-linked dissociation in hemoglobin from the sea cucumber Molpadia arenicola. It has been established that Molpadia hemoglobin tends to dissociate into subunits as oxygen is bound. The kinetics and equilibria of carbon monoxide and ethylisocyanide binding reported here show a dependence on protein concentration that supports the conclusion that the aggregated hemoglobin has a lower ligand affinity than the dissociated subunits. This is true for the isolated D-chain as well as for the unfractionated hemolysate that contains four distinct polypeptide chains (A-D). This indicates that even homopolymers of Molpadia hemoglobin have lower ligand affinity than the dissociated subunits. At high protein concentration hemolysates of Molpadia hemoglobin show slight cooperativity. The time course of ligand binding to the deoxy D-chain also suggests cooperative interactions. The low affinity of the aggregated state may have a different molecular explanation than in human hemoglobin where tetramers of identical subunits (as in Hb H) show high oxygen affinity. The absence of tyrosine and histidine at the C-terminal of the Molpadia D-chains also suggests a different stabilization of the low affinity deoxy state. An additional functional difference between Molpadia hemoglobin and human hemoglobin is that organic phosphates do not alter the ligand affinity of the sea cucumber hemoglobin."} {"id": "PMID:1276183", "title": "Mechanism for the interaction of thiols with methylcobalamin.", "content": "The reaction between methylcobalamin and ethane-thiol sulfonic acid (Co-enzyme M) has been studied under aerobic conditions. For this reaction evidence is presented for a catalytic cycle which promotes homolytic cleavage of the Cobalt-carbon sigma-bond to give Cob(II)alamin (B12-r) and methylcoenzyme M as the products. This reaction is especially pertinent to our understanding of the mechanism of methane-biosynthesis. In addition, we have used 220 MHZ 1H NMR and 13C NMR to show that thiols do not react with methylcorrinoids by displacing the base trans-axial to the cobalt-carbon bond. This NMR study is especially important since the co-ordination of thiols to cobalt has previously been reported to occur by a number of research groups including our own.", "contents": "Mechanism for the interaction of thiols with methylcobalamin. The reaction between methylcobalamin and ethane-thiol sulfonic acid (Co-enzyme M) has been studied under aerobic conditions. For this reaction evidence is presented for a catalytic cycle which promotes homolytic cleavage of the Cobalt-carbon sigma-bond to give Cob(II)alamin (B12-r) and methylcoenzyme M as the products. This reaction is especially pertinent to our understanding of the mechanism of methane-biosynthesis. In addition, we have used 220 MHZ 1H NMR and 13C NMR to show that thiols do not react with methylcorrinoids by displacing the base trans-axial to the cobalt-carbon bond. This NMR study is especially important since the co-ordination of thiols to cobalt has previously been reported to occur by a number of research groups including our own."} {"id": "PMID:1276184", "title": "Correlation between flash-induced oxygen evolution and fluorescence yield kinetics in the 0 to 16 mus range in Chlorella pyyrenoidosa during incubation with hydroxylamine.", "content": "Following flash excitation, oxygen pulses and fluorescence kinetics in the time range 0-16 mus were studied in the alga Chlorella pyrenoidosa during incubation with various concentrations of hydroxylamine. The obtained results could be explained considering four effects of hydroxylamine. 1. Hydroxylamine removes (reduces) oxidizing equivalents, generated in the water-splitting system by flash excitation. This process does not markedly affect the fluorescence yield kinetics between 0 and 16 mus following the ignition of a flash and reaches a constant rate within a few minutes, but possibly within a few seconds, after addition of hydroxylamine. In a sequence of flashes separated by dark time td, the steady-state oxygen yield in the flashes is exp(-ktd), the yield at td=0 being taken equal to 1, where k=(0.1 + beta[NH2OH])s-1, with [NH2OH] in mM and beta=0.6 mM-1, provided [NH2OH]greater than or equal to 0.5 mM. 2. An inhibition between Z, the physiological donor and the oxidized reaction center pigment P+ occurs, proceeding as exp (-kiti)where ti is the incubation time with hydroxylamine and ki=(alpha[NH2OH]) min-1, with [NH2OH] in mM and alpha=0.14 mM-1. This process not only inhibits oxygen evolution capability, but also decreases the amplitude of the fluorescence yield difference deltaphi=phi(16 mus)-phi(2 mus) induced by a flesh in the steady state. In a fraction of the reaction centers this inhibition occurs \"immediately\" after the addition of hydroxylamine. These observations, combined with the conslusion of Cheniae and Martin (1971, Plant Physiol. 47, 568-575) that the inhibition of the Hill reaction is related to the extraction of bound manganese indicate that the reaction between Z and P+ requires bound manganese. 3. In the inhibited centers a second donor for P+, D, connected to an entry site for the artificial electron donor hydroxylamine becomes apparent. 4. A flash-induced oxygen uptake signal was observed in the presence of hydroxylamine, which was shown to be caused by a system II reaction. The effects under (1) and (4) were reversed in the dark if hydroxylamine was removed by washing. The effects under (2) and (3) were reversed during illumination of a washed sample.", "contents": "Correlation between flash-induced oxygen evolution and fluorescence yield kinetics in the 0 to 16 mus range in Chlorella pyyrenoidosa during incubation with hydroxylamine. Following flash excitation, oxygen pulses and fluorescence kinetics in the time range 0-16 mus were studied in the alga Chlorella pyrenoidosa during incubation with various concentrations of hydroxylamine. The obtained results could be explained considering four effects of hydroxylamine. 1. Hydroxylamine removes (reduces) oxidizing equivalents, generated in the water-splitting system by flash excitation. This process does not markedly affect the fluorescence yield kinetics between 0 and 16 mus following the ignition of a flash and reaches a constant rate within a few minutes, but possibly within a few seconds, after addition of hydroxylamine. In a sequence of flashes separated by dark time td, the steady-state oxygen yield in the flashes is exp(-ktd), the yield at td=0 being taken equal to 1, where k=(0.1 + beta[NH2OH])s-1, with [NH2OH] in mM and beta=0.6 mM-1, provided [NH2OH]greater than or equal to 0.5 mM. 2. An inhibition between Z, the physiological donor and the oxidized reaction center pigment P+ occurs, proceeding as exp (-kiti)where ti is the incubation time with hydroxylamine and ki=(alpha[NH2OH]) min-1, with [NH2OH] in mM and alpha=0.14 mM-1. This process not only inhibits oxygen evolution capability, but also decreases the amplitude of the fluorescence yield difference deltaphi=phi(16 mus)-phi(2 mus) induced by a flesh in the steady state. In a fraction of the reaction centers this inhibition occurs \"immediately\" after the addition of hydroxylamine. These observations, combined with the conslusion of Cheniae and Martin (1971, Plant Physiol. 47, 568-575) that the inhibition of the Hill reaction is related to the extraction of bound manganese indicate that the reaction between Z and P+ requires bound manganese. 3. In the inhibited centers a second donor for P+, D, connected to an entry site for the artificial electron donor hydroxylamine becomes apparent. 4. A flash-induced oxygen uptake signal was observed in the presence of hydroxylamine, which was shown to be caused by a system II reaction. The effects under (1) and (4) were reversed in the dark if hydroxylamine was removed by washing. The effects under (2) and (3) were reversed during illumination of a washed sample."} {"id": "PMID:1276185", "title": "Enhancement studies on algae and isolated chloroplasts. Part I. Variability of photosynthetic enhancement in Chlorella pyrenoidosa.", "content": "Studies of the variability of enhancement in Chlorella pyrenoidosa confirm the existence of two types of variability: a very slow diurnal variation linked to the growth cycle and a much more rapid adaptive response to the immediate incident light conditions (State I-State II transitions). Measurements of the wavelength dependencies and relative contributions of these two types of variability suggest that they may be linked. A close examination of the enhancement signals associated with the State I-State II transition reveals that the transitions can take place in any one of three ways: by a change in Photosystem II efficiency alone, by a change in Photosystem I efficiency alone or by a simultaneous change in the efficiencies of both photo systems. Measurements of the rates of transition between State I, State II and the dark adapted state, Dark, suggest that the behaviour of State II and Dark are normally, but not always, identical. The transitions between the three states were found to be first order. For those samples exhibiting the same behaviour in Dark and State II, the rate of the State I-State II transition was found to be independent of the wavelength of Light II, suggesting that the return from State I to State II is essentially a dark process and that the driving force for the adaptive transition is the over-stimulation of Photosystem I. Finally, a model is proposed, involving an antagonistic control of the quantum yields of photochemistry of the two photosystems, that is capable of explaining the links between the two types of variability, their wavelength dependencies and the shapes of the individual enhancement signals.", "contents": "Enhancement studies on algae and isolated chloroplasts. Part I. Variability of photosynthetic enhancement in Chlorella pyrenoidosa. Studies of the variability of enhancement in Chlorella pyrenoidosa confirm the existence of two types of variability: a very slow diurnal variation linked to the growth cycle and a much more rapid adaptive response to the immediate incident light conditions (State I-State II transitions). Measurements of the wavelength dependencies and relative contributions of these two types of variability suggest that they may be linked. A close examination of the enhancement signals associated with the State I-State II transition reveals that the transitions can take place in any one of three ways: by a change in Photosystem II efficiency alone, by a change in Photosystem I efficiency alone or by a simultaneous change in the efficiencies of both photo systems. Measurements of the rates of transition between State I, State II and the dark adapted state, Dark, suggest that the behaviour of State II and Dark are normally, but not always, identical. The transitions between the three states were found to be first order. For those samples exhibiting the same behaviour in Dark and State II, the rate of the State I-State II transition was found to be independent of the wavelength of Light II, suggesting that the return from State I to State II is essentially a dark process and that the driving force for the adaptive transition is the over-stimulation of Photosystem I. Finally, a model is proposed, involving an antagonistic control of the quantum yields of photochemistry of the two photosystems, that is capable of explaining the links between the two types of variability, their wavelength dependencies and the shapes of the individual enhancement signals."} {"id": "PMID:1276186", "title": "Enhancement studies on algae and isolated chloroplasts. Part II. Enhancement of oxygen evolution in intact chloroplasts.", "content": "Intact isolated chloroplasts were shown to exhibit a characteristic three-phase pattern of development of oxygen evolution activity. The first phase, Phase I, appeared to be an equilibration phase in which the isolated chloroplasts adapted to the conditions on the electrode surface. It was characterised by a rapidly increasing rate of oxygen evolution accompanied by decreasing enhancement signals. The second phase, Phase II, was an intermediate phase in which the rate of oxygen evolution was maximal and no enhancement was observed. In the last phase, Phase III, the rate of oxygen fell again, normal enhancement was still missing, but the samples appeared to undergo slow adaptive changes closely related to the State I-State II changes previously reported for whole cell systems. The concentrations of Mg2+ within the chloroplast were shown to play an important role in the control of the development of both the oxygen evolution and enhancement signals. It was shown how these signals could be explained in terms of a model that was consistent with that developed in Part I of this investigation to account for the variability of enhancement of the alga Chlorella pyrenoidosa.", "contents": "Enhancement studies on algae and isolated chloroplasts. Part II. Enhancement of oxygen evolution in intact chloroplasts. Intact isolated chloroplasts were shown to exhibit a characteristic three-phase pattern of development of oxygen evolution activity. The first phase, Phase I, appeared to be an equilibration phase in which the isolated chloroplasts adapted to the conditions on the electrode surface. It was characterised by a rapidly increasing rate of oxygen evolution accompanied by decreasing enhancement signals. The second phase, Phase II, was an intermediate phase in which the rate of oxygen evolution was maximal and no enhancement was observed. In the last phase, Phase III, the rate of oxygen fell again, normal enhancement was still missing, but the samples appeared to undergo slow adaptive changes closely related to the State I-State II changes previously reported for whole cell systems. The concentrations of Mg2+ within the chloroplast were shown to play an important role in the control of the development of both the oxygen evolution and enhancement signals. It was shown how these signals could be explained in terms of a model that was consistent with that developed in Part I of this investigation to account for the variability of enhancement of the alga Chlorella pyrenoidosa."} {"id": "PMID:1276187", "title": "Photoinduction kinetics of electrical potential in a single chloroplast as studied with micro-electrode technique.", "content": "1. Using single chloroplasts of Peperomia metallica the kinetics of light-induced potential changes were studied. Three kinetic components (the initial fast rise, the decay in the light and the decay in the dark) were found to be characterized by time constants 4, 220 and 60 ms, respectively at light intensity 5000 1x and temperature 18 degrees C. After flash excitation the potential kept on rising for about 10 ms. Cooling of the medium down to 5 degrees C had no effect on the duration of potential rise after the flash. 2. Variations in the medium temperature in the range 2-23 degrees C had little effect on photoresponse magnitude but resulted in significant acceleration of decay in the light. 3. Addition of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (5-)0(-6) M) resulted in suppression of the magnitude of the photoresponse but was not accompanied by any change in the rate of initial rise of potential. 3-(3,4-Dichlorophenyl)-1,1-dimethylurea-inhibited photoresponse could be restored and even enhanced by subsequent addition of N-methylphenazonium methosulfate (10(-4) M). N-Methylphenazonium methosulfate essentially influenced the time course and light-intensity curves of photoresponse. 4. The chloroplast photoresponses were of different time-courses when elicited by red (640 nm) or far red (712 nm) light. This fact as well as an enhancement effect of combined illumination by two intermittent light beams indicate on the interaction of two photosynthetic pigment systems when the photoelectric response was formed. 5. An imposed electrical field resulted in stimulation or suppression of chloroplast photoresponse depending on the polarity of the field. No indications for the existance of \"reversal potential\" for photoelectric response were obtained. 6. A kinetic scheme of photoresponse formation is proposed, which includes two sequential photochemical reactions of photosynthesis.", "contents": "Photoinduction kinetics of electrical potential in a single chloroplast as studied with micro-electrode technique. 1. Using single chloroplasts of Peperomia metallica the kinetics of light-induced potential changes were studied. Three kinetic components (the initial fast rise, the decay in the light and the decay in the dark) were found to be characterized by time constants 4, 220 and 60 ms, respectively at light intensity 5000 1x and temperature 18 degrees C. After flash excitation the potential kept on rising for about 10 ms. Cooling of the medium down to 5 degrees C had no effect on the duration of potential rise after the flash. 2. Variations in the medium temperature in the range 2-23 degrees C had little effect on photoresponse magnitude but resulted in significant acceleration of decay in the light. 3. Addition of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (5-)0(-6) M) resulted in suppression of the magnitude of the photoresponse but was not accompanied by any change in the rate of initial rise of potential. 3-(3,4-Dichlorophenyl)-1,1-dimethylurea-inhibited photoresponse could be restored and even enhanced by subsequent addition of N-methylphenazonium methosulfate (10(-4) M). N-Methylphenazonium methosulfate essentially influenced the time course and light-intensity curves of photoresponse. 4. The chloroplast photoresponses were of different time-courses when elicited by red (640 nm) or far red (712 nm) light. This fact as well as an enhancement effect of combined illumination by two intermittent light beams indicate on the interaction of two photosynthetic pigment systems when the photoelectric response was formed. 5. An imposed electrical field resulted in stimulation or suppression of chloroplast photoresponse depending on the polarity of the field. No indications for the existance of \"reversal potential\" for photoelectric response were obtained. 6. A kinetic scheme of photoresponse formation is proposed, which includes two sequential photochemical reactions of photosynthesis."} {"id": "PMID:1276188", "title": "Further evidence for a phycobilisome model from selective dissociation, fluorescence emission, immunoprecipitation, and electron microscopy.", "content": "Phycobilisomes, isolated in 500 mM Sorensen's phosphate buffer pH 6.8 from the red alga, Porphyridium cruetum, were analyzed by selective dissociation at various phosphate concentrations. The results are consistent with a structural model consisting of an allophycocyanin core, surrounding by a hemispherical layer of R-phycocyanin, with phycoerythrin being on the periphery. Such a structure also allows maximum energy transfer. Intact phycobilisomes transfer excitation energy ultimately to a pigment with a fluorescence emission maximum at 675 nm. This pigment is presumed to be allophycocyanin in an aggreagated state. Uncoupling of energy transfer among the pigments, and physical release of the phycobiliproteins from the phycobilisome follow a parallel time-course; phycoerythrin is released first, followed by R-phycocyanin, and then allophycocyanin. In 55 mM phosphate buffer, the times at which 50% of each phycobiliprotein has dissociated are: phycoerythrin 40 min, R-phycocyanin 75 min, and allophycocyanin 140 min. The proposed arrangement of phycobiliproteins within phycobilisomes is also consistent with the results from precipitation reactions with monospecific antisera on intact and dissociated phycobilisomes. Anti-phycoertythrin reacts almost immediately with intact phycobilisomes, but reactivity with anti-R-phycocyanin and anti-allophycocyanin is considerably delayed, suggesting that the antigens are not accessible until a loosening of the phycobilsome structure occurs. Reaction wbilisomes, but is much more rapid in phycobilisomes of Nostoc sp. which contains 6-8 times more allophycocyanin. It is proposed that allophycocyanin is partially exposed on the base of isolated intact phycobilisomes of both algae, but that in P. cruentum there are too few accessible sites to permit a rapid formation of a precipitate with anti-allophyocyanin.", "contents": "Further evidence for a phycobilisome model from selective dissociation, fluorescence emission, immunoprecipitation, and electron microscopy. Phycobilisomes, isolated in 500 mM Sorensen's phosphate buffer pH 6.8 from the red alga, Porphyridium cruetum, were analyzed by selective dissociation at various phosphate concentrations. The results are consistent with a structural model consisting of an allophycocyanin core, surrounding by a hemispherical layer of R-phycocyanin, with phycoerythrin being on the periphery. Such a structure also allows maximum energy transfer. Intact phycobilisomes transfer excitation energy ultimately to a pigment with a fluorescence emission maximum at 675 nm. This pigment is presumed to be allophycocyanin in an aggreagated state. Uncoupling of energy transfer among the pigments, and physical release of the phycobiliproteins from the phycobilisome follow a parallel time-course; phycoerythrin is released first, followed by R-phycocyanin, and then allophycocyanin. In 55 mM phosphate buffer, the times at which 50% of each phycobiliprotein has dissociated are: phycoerythrin 40 min, R-phycocyanin 75 min, and allophycocyanin 140 min. The proposed arrangement of phycobiliproteins within phycobilisomes is also consistent with the results from precipitation reactions with monospecific antisera on intact and dissociated phycobilisomes. Anti-phycoertythrin reacts almost immediately with intact phycobilisomes, but reactivity with anti-R-phycocyanin and anti-allophycocyanin is considerably delayed, suggesting that the antigens are not accessible until a loosening of the phycobilsome structure occurs. Reaction wbilisomes, but is much more rapid in phycobilisomes of Nostoc sp. which contains 6-8 times more allophycocyanin. It is proposed that allophycocyanin is partially exposed on the base of isolated intact phycobilisomes of both algae, but that in P. cruentum there are too few accessible sites to permit a rapid formation of a precipitate with anti-allophyocyanin."} {"id": "PMID:1276189", "title": "Phase transitions of phospholipid single-wall vesicles and multilayers. Measurement by vibrational Raman spectroscopic frequency differences.", "content": "Raman spectroscopic frequency differences between selected carbon-carbon stretching modes of lipid hydrocarbon chains were determined as a function of temperature for use in monitoring lipid phase transition behavior and acyl chain disorder in both multilamellar and single-wall vesicles. Transition temperatures detected by this procedure for pure dipalmitoyl phosphatidylcholine and dimyristoyl phosphatidylcholine multilayers were observed at 39 +/- 1 degrees C and 23 +/- 1 degrees C, respectively. Although the phase transition for unilamellar vesicles of dipalmitoyl phosphatidylcholine occurred at nearly the same temperature as the multilayers, the crystal-liquid crystalline transition for the single-shell vesicles appeared to span a slightly broader temperature range, a characteristic consistent with irregularities in the packing arrangement of the hydrocarbon chains. Within the precision of the Raman spectroscopic method, however, the temperature behavior of both the multilamellar and the unilamellar dimyristoyl phosphatidylcholine assemblies appeared nearly identical. The temperature profile for the Raman frequency differences of an excess water sonicate of 25 mol percent cholesterol in dipalmitoyl phosphatidylcholine served as an example of the effect upon lipid phase transition characteristics of a bilayer component intercalated between the acyl chains. For this particular cholesterol-lipid system the phase transition was broadened over a 30 degrees C temperature range, in contrast to the marrow 2-4 degrees C range observed for pure multilayer and single-shell vesicle particles.", "contents": "Phase transitions of phospholipid single-wall vesicles and multilayers. Measurement by vibrational Raman spectroscopic frequency differences. Raman spectroscopic frequency differences between selected carbon-carbon stretching modes of lipid hydrocarbon chains were determined as a function of temperature for use in monitoring lipid phase transition behavior and acyl chain disorder in both multilamellar and single-wall vesicles. Transition temperatures detected by this procedure for pure dipalmitoyl phosphatidylcholine and dimyristoyl phosphatidylcholine multilayers were observed at 39 +/- 1 degrees C and 23 +/- 1 degrees C, respectively. Although the phase transition for unilamellar vesicles of dipalmitoyl phosphatidylcholine occurred at nearly the same temperature as the multilayers, the crystal-liquid crystalline transition for the single-shell vesicles appeared to span a slightly broader temperature range, a characteristic consistent with irregularities in the packing arrangement of the hydrocarbon chains. Within the precision of the Raman spectroscopic method, however, the temperature behavior of both the multilamellar and the unilamellar dimyristoyl phosphatidylcholine assemblies appeared nearly identical. The temperature profile for the Raman frequency differences of an excess water sonicate of 25 mol percent cholesterol in dipalmitoyl phosphatidylcholine served as an example of the effect upon lipid phase transition characteristics of a bilayer component intercalated between the acyl chains. For this particular cholesterol-lipid system the phase transition was broadened over a 30 degrees C temperature range, in contrast to the marrow 2-4 degrees C range observed for pure multilayer and single-shell vesicle particles."} {"id": "PMID:1276190", "title": "Enzymic solubilization of the human intestinal brush border membrane enzymes.", "content": "The releases of proteins, maltase, lactase, sucrase, trehalase, alkaline phosphatase, gamma-glutamyltransferase and leucylnaphthylamide-hydrolyzing activity from human intestinal brush bborder membrane vesicles by various enzymes (especially pancreatic proteases) have been studied. The brush border membrane enzymes are not solubilized by digestion with trypsin and chymotrypsin but are largely released after treatment with papain or elastase. Most of the enzymes are fully active after the proteolytic treatment. All proteins released by papain and elastase have been identified by electrophoresis to already known intestinal hydrolases. Electron microscopy of brush border membrane vesicles demonstrates \"knob-like\" structures (particles) attached to the external side of the membrane. During papain treatment, enzyme removal runs parallel with the disappearance of the particles. During elastase treatment it is not possible to correlate the release of the enzymic activities with the removal of the particles. The results indicate that most of the intestinal hydrolases are surface components attached to the external side of the membrane. They are in accord with the concept that the brush border membrane enzymes are organized within the membrane in a mosaic-like pattern.", "contents": "Enzymic solubilization of the human intestinal brush border membrane enzymes. The releases of proteins, maltase, lactase, sucrase, trehalase, alkaline phosphatase, gamma-glutamyltransferase and leucylnaphthylamide-hydrolyzing activity from human intestinal brush bborder membrane vesicles by various enzymes (especially pancreatic proteases) have been studied. The brush border membrane enzymes are not solubilized by digestion with trypsin and chymotrypsin but are largely released after treatment with papain or elastase. Most of the enzymes are fully active after the proteolytic treatment. All proteins released by papain and elastase have been identified by electrophoresis to already known intestinal hydrolases. Electron microscopy of brush border membrane vesicles demonstrates \"knob-like\" structures (particles) attached to the external side of the membrane. During papain treatment, enzyme removal runs parallel with the disappearance of the particles. During elastase treatment it is not possible to correlate the release of the enzymic activities with the removal of the particles. The results indicate that most of the intestinal hydrolases are surface components attached to the external side of the membrane. They are in accord with the concept that the brush border membrane enzymes are organized within the membrane in a mosaic-like pattern."} {"id": "PMID:1276191", "title": "Distribution of protein-bound sugar residues in microsomal subfractions and Golgi membranes.", "content": "Liver microsomal subfractions and Golgi membranes free from adsorbed and secretory proteins have a characteristic sugar composition. The ratio of mannose to galactose is largest in rough microsomes, smaller in smooth I microsomes, still smaller in smooth II microsomes, and smallest in Golgi membranes. There is about twice as much glucosamine in Golgi membranes and 3 times as much in smooth II microsomes as in the other microsomal subfractions. Golgi membranes are rich in sialic acid in comparison to rough microsomes and it is present at even higher levels in the two smooth microsomal subfractions. Increasing concentrations of deoxycholate preferentially remove protein-bound mannose and glucosamine, while releasing significantly less galactose. About half of the microsomal mannose and galactose can be liberated from the surface of intact microsomal vesicles by treatment with trypsin. When trypsin is added to permeable vesicles where the inside surface can be also attacked, an additional 20% of the total mannose but no additional galactose is liberated.", "contents": "Distribution of protein-bound sugar residues in microsomal subfractions and Golgi membranes. Liver microsomal subfractions and Golgi membranes free from adsorbed and secretory proteins have a characteristic sugar composition. The ratio of mannose to galactose is largest in rough microsomes, smaller in smooth I microsomes, still smaller in smooth II microsomes, and smallest in Golgi membranes. There is about twice as much glucosamine in Golgi membranes and 3 times as much in smooth II microsomes as in the other microsomal subfractions. Golgi membranes are rich in sialic acid in comparison to rough microsomes and it is present at even higher levels in the two smooth microsomal subfractions. Increasing concentrations of deoxycholate preferentially remove protein-bound mannose and glucosamine, while releasing significantly less galactose. About half of the microsomal mannose and galactose can be liberated from the surface of intact microsomal vesicles by treatment with trypsin. When trypsin is added to permeable vesicles where the inside surface can be also attacked, an additional 20% of the total mannose but no additional galactose is liberated."} {"id": "PMID:1276192", "title": "The ATP dependence of a ouabain-sensitive sodium efflux activated by external sodium, potassium and lithium in human red cells.", "content": "The stimulation of ouabain-sensitive Na+ efflux by external Na+, K+ and Li+ was studied in control and ATP-depleted human red cells. In the presence of 5 mM Na+, with control and depleted cells, Li+ stimulated with a lower apparent affinity than K+, and gave a smaller maximal activation than K+. The ability of Na+, K+ and Li+ to activate Na+ efflux was a function of the ATP content of the cells. Relative to K+ both Na+ and Li+ became more effective activators when the ATP was reduced to about one tenth of the control values. At this low ATP concentration Na+ was absolutely more effective than K+.", "contents": "The ATP dependence of a ouabain-sensitive sodium efflux activated by external sodium, potassium and lithium in human red cells. The stimulation of ouabain-sensitive Na+ efflux by external Na+, K+ and Li+ was studied in control and ATP-depleted human red cells. In the presence of 5 mM Na+, with control and depleted cells, Li+ stimulated with a lower apparent affinity than K+, and gave a smaller maximal activation than K+. The ability of Na+, K+ and Li+ to activate Na+ efflux was a function of the ATP content of the cells. Relative to K+ both Na+ and Li+ became more effective activators when the ATP was reduced to about one tenth of the control values. At this low ATP concentration Na+ was absolutely more effective than K+."} {"id": "PMID:1276193", "title": "Transport of 3-O-methyl D-glucose and beta-methyl D-glucoside by rabbit ileum.", "content": "The intestinal transport of three actively transported sugars has been studied in order to determine mechanistic features that, (a) can be attributed to stereo-specific affinity and (b) are common. The apparent affinity constants at the brush-border indicate that sugars are selected in the order, beta-methyl glucose greater than D-galactose greater than 3-O-methyl glucose, (the Km values are 1.23, 5.0 and 18.1 mM, respectively.) At low substrate concentrations the Kt values for Na+ activation of sugar entry across the brush-border are: 27, 25, and 140 mequiv. for beta-methyl glucose, galactose and 3-O-methyl glucose, respectively. These kinetic parameters suggest that Na+, water, sugar and membrane-binding groups are all factors which determine selective affinity. In spite of these differences in operational affinity, all three sugars show a reciprocal change in brush-border entry and exit permeability as Ringer (Na) or (sugar) is increased. Estimates of the changes in convective velocity and in the diffusive velocity when the sugar concentration in the Ringer is raised reveal that with all three sugars, the fractional reduction in convective velocity is approximately equal to the (reduction of diffusive velocity)2. This is consistent with the view that the sugars move via pores in the brush-border by convective diffusion. Theophylline reduces the serosal border permeability to beta-methyl glucose and to 3-O-methyl glucose relatively by the same extent and consequently, increase the intracellular accumulation of these sugars. The permeability of the serosal border to beta-methyl glucose entry is lower than permeability of the serosal border to beta-methyl glucose exit, which suggested that beta-methyl glucose may be convected out of the cell across the lateral serosal border.", "contents": "Transport of 3-O-methyl D-glucose and beta-methyl D-glucoside by rabbit ileum. The intestinal transport of three actively transported sugars has been studied in order to determine mechanistic features that, (a) can be attributed to stereo-specific affinity and (b) are common. The apparent affinity constants at the brush-border indicate that sugars are selected in the order, beta-methyl glucose greater than D-galactose greater than 3-O-methyl glucose, (the Km values are 1.23, 5.0 and 18.1 mM, respectively.) At low substrate concentrations the Kt values for Na+ activation of sugar entry across the brush-border are: 27, 25, and 140 mequiv. for beta-methyl glucose, galactose and 3-O-methyl glucose, respectively. These kinetic parameters suggest that Na+, water, sugar and membrane-binding groups are all factors which determine selective affinity. In spite of these differences in operational affinity, all three sugars show a reciprocal change in brush-border entry and exit permeability as Ringer (Na) or (sugar) is increased. Estimates of the changes in convective velocity and in the diffusive velocity when the sugar concentration in the Ringer is raised reveal that with all three sugars, the fractional reduction in convective velocity is approximately equal to the (reduction of diffusive velocity)2. This is consistent with the view that the sugars move via pores in the brush-border by convective diffusion. Theophylline reduces the serosal border permeability to beta-methyl glucose and to 3-O-methyl glucose relatively by the same extent and consequently, increase the intracellular accumulation of these sugars. The permeability of the serosal border to beta-methyl glucose entry is lower than permeability of the serosal border to beta-methyl glucose exit, which suggested that beta-methyl glucose may be convected out of the cell across the lateral serosal border."} {"id": "PMID:1276194", "title": "Effect of alkali ions on the active transport of neutral amino acids into Streptomyces hydrogenans.", "content": "The active transport of neutral amino acids into Streptomyces hydrogenans is inhibited by external Na+. There is no indication that in these cells amino acid accumulation is driven by an inward gradient of Na+. The extent of transport inhibition by Na+ depends on the nature of the amino acid. It decreases with increasing chain length of the amino acid molecules i.e. with increasing non-polar properties of the side chain. Kinetic studies show that Na+ competes with the amino acid for a binding site at the amino acid carrier. There is a close relation between the Ki values for Na+ and the number of C atoms of the amino acids. Other cations also inhibit neutral amino acid uptake competitively; the effectiveness decreases in the order Li+ greater than Na+ greater than K+ greater than Rb+ greater than Cs+. Anions do not have a significant effect on the uptake of neutral amino acids. After prolonged incubation of the cells with 150 mM Na+, in addition to the competitive inhibition of transport Na+ induces an increase in membrane permeability for amino acids.", "contents": "Effect of alkali ions on the active transport of neutral amino acids into Streptomyces hydrogenans. The active transport of neutral amino acids into Streptomyces hydrogenans is inhibited by external Na+. There is no indication that in these cells amino acid accumulation is driven by an inward gradient of Na+. The extent of transport inhibition by Na+ depends on the nature of the amino acid. It decreases with increasing chain length of the amino acid molecules i.e. with increasing non-polar properties of the side chain. Kinetic studies show that Na+ competes with the amino acid for a binding site at the amino acid carrier. There is a close relation between the Ki values for Na+ and the number of C atoms of the amino acids. Other cations also inhibit neutral amino acid uptake competitively; the effectiveness decreases in the order Li+ greater than Na+ greater than K+ greater than Rb+ greater than Cs+. Anions do not have a significant effect on the uptake of neutral amino acids. After prolonged incubation of the cells with 150 mM Na+, in addition to the competitive inhibition of transport Na+ induces an increase in membrane permeability for amino acids."} {"id": "PMID:1276195", "title": "Changes in amino acid transport in the rat pancreas in response to fasting and feeding.", "content": "Transport of amino acids (in vitro) in the rat pancreas is affected by the nutritional state of the animal. A fast of 24 h (young animals) or 48 h (adult animals) reduces the rate of amino acid uptake in the isolated rat pancreas in vitro. In contrast, refeeding of animals after a fast shows an increase in transport in young as well as adult animals. The effects of refeeding after a fast are mimicked to a significant extent by injection of mixtures of pancreozymin and carbamylcholine. Addition of these agents in vitro has no effect. The incorporation of amino acids into the total proteins of the rat pancreas follows the pattern of amino acid uptake. Even at high external levels of glycine (5 mM), incorporation increases although the glycine level in the cell is in excess of 25 mM. Reduction of glycine uptake by ouabain by 75% results in a substantial (44%) diminution of amino acid incorporation into proteins. The data suggest that inhibition of amino acid incorporation under the various metabolic conditions examined is due largely to a decreased availability of amino acids.", "contents": "Changes in amino acid transport in the rat pancreas in response to fasting and feeding. Transport of amino acids (in vitro) in the rat pancreas is affected by the nutritional state of the animal. A fast of 24 h (young animals) or 48 h (adult animals) reduces the rate of amino acid uptake in the isolated rat pancreas in vitro. In contrast, refeeding of animals after a fast shows an increase in transport in young as well as adult animals. The effects of refeeding after a fast are mimicked to a significant extent by injection of mixtures of pancreozymin and carbamylcholine. Addition of these agents in vitro has no effect. The incorporation of amino acids into the total proteins of the rat pancreas follows the pattern of amino acid uptake. Even at high external levels of glycine (5 mM), incorporation increases although the glycine level in the cell is in excess of 25 mM. Reduction of glycine uptake by ouabain by 75% results in a substantial (44%) diminution of amino acid incorporation into proteins. The data suggest that inhibition of amino acid incorporation under the various metabolic conditions examined is due largely to a decreased availability of amino acids."} {"id": "PMID:1276196", "title": "Changes of nonelectrolyte permeability in cholesterol-loaded erythrocytes.", "content": "Membrane cholesterol in porcine and bovine erythrocytes was elevated up to 165% of its normal value by incubation of the cells in cholesterol/phosphatidylcholine dispersions with or without serum. This alteration of membrane lipid composition brought about only a minor (10-40%) decrease of the permeability to glycerol, erythritol and to organic acids penetrating by non-ionic diffusion, although additional cholesterol had actually been incorporated into the lipid bilayer, as indicated by determinations of cell surface area from the critical hemolytic volume, in combination with quantitative evaluation of freeze-etch electron micrographs. On the basis of this finding and of the previously demonstrated (Grunze, M. and Deuticke, B. (1974) Biochim. Biophys. Acta 356, 125-130) considerable increase of permeability in cholesterol-depleted cells, it is proposed that in the erythrocyte membrane a pronounced \"specific\" reduction of permeability by cholesterol occurs only up to a molar ratio cholesterol/polar lipid of 0.6. At higher ratios cholesterol affects permeability only slightly, owing to an \"unspecific\" rigidifying effect on the membrane lipid phase.", "contents": "Changes of nonelectrolyte permeability in cholesterol-loaded erythrocytes. Membrane cholesterol in porcine and bovine erythrocytes was elevated up to 165% of its normal value by incubation of the cells in cholesterol/phosphatidylcholine dispersions with or without serum. This alteration of membrane lipid composition brought about only a minor (10-40%) decrease of the permeability to glycerol, erythritol and to organic acids penetrating by non-ionic diffusion, although additional cholesterol had actually been incorporated into the lipid bilayer, as indicated by determinations of cell surface area from the critical hemolytic volume, in combination with quantitative evaluation of freeze-etch electron micrographs. On the basis of this finding and of the previously demonstrated (Grunze, M. and Deuticke, B. (1974) Biochim. Biophys. Acta 356, 125-130) considerable increase of permeability in cholesterol-depleted cells, it is proposed that in the erythrocyte membrane a pronounced \"specific\" reduction of permeability by cholesterol occurs only up to a molar ratio cholesterol/polar lipid of 0.6. At higher ratios cholesterol affects permeability only slightly, owing to an \"unspecific\" rigidifying effect on the membrane lipid phase."} {"id": "PMID:1276197", "title": "Saturable binding to cell membranes of the presynaptic neurotoxin, beta-bungarotoxin.", "content": "Brief exposure to the protein neurotoxin, beta-bungarotoxin, is known to disrupt neuromuscular transmission irreversibly by blocking the release of transmitter from the nerve terminal. This neurotoxin also has a phospholipase A2 activity, although phospholipases in general are not very toxic. To determine if the toxicity of this molecule might result from specific binding to neural tissue, we have looked for high affinity, saturable binding using 125I-labelled toxin. At low membrane protein concentration 125I-labeled toxin binding was directly proportional to the amount of membrane; at fixed membrane concentration 125I-labeled toxin showed saturable binding. It was unlikely that iodination markedly changed the toxin's properties since the iodinated toxin had a comparable binding affinity to that of native toxin as judged by competition experiments. Comparison of toxin binding to brain, liver and red blood cell membranes showed that all had high affinity binding sites with dissociation constants between one and two nanomolar. This is comparable to the concentrations previously shown to inhibit mitochondrial function. However, the density of these sites showed marked variation such that the density of sites was 13.0 pmol/mg protein for a brain membrane preparation, 2.4 pmol/mg for liver and 0.25 pmol/mg for red blood cell membranes. In earlier work we had shown that calcium uptake by brain mitochondria is inhibited at much lower toxin concentrations than is liver mitochondrial uptake. Both liver and brain mitochondria bind toxin specifically, but the density of 125I-labeled toxin binding sites on brain mitochondrial preparations (3.3 +/- 0.3 pmol/mg) exceeded by a factor of ten the density on liver mitochondrial preparations (0.3 +/- 0.05 pmol/mg). It is also shown that labeled toxin does not cross synaptosomal membranes, suggesting that mitochondria may not be the site of action of the toxin in vivo. We conclude that beta-bungarotoxin is an enzyme which can bind specifically with high affinity to cell membranes.", "contents": "Saturable binding to cell membranes of the presynaptic neurotoxin, beta-bungarotoxin. Brief exposure to the protein neurotoxin, beta-bungarotoxin, is known to disrupt neuromuscular transmission irreversibly by blocking the release of transmitter from the nerve terminal. This neurotoxin also has a phospholipase A2 activity, although phospholipases in general are not very toxic. To determine if the toxicity of this molecule might result from specific binding to neural tissue, we have looked for high affinity, saturable binding using 125I-labelled toxin. At low membrane protein concentration 125I-labeled toxin binding was directly proportional to the amount of membrane; at fixed membrane concentration 125I-labeled toxin showed saturable binding. It was unlikely that iodination markedly changed the toxin's properties since the iodinated toxin had a comparable binding affinity to that of native toxin as judged by competition experiments. Comparison of toxin binding to brain, liver and red blood cell membranes showed that all had high affinity binding sites with dissociation constants between one and two nanomolar. This is comparable to the concentrations previously shown to inhibit mitochondrial function. However, the density of these sites showed marked variation such that the density of sites was 13.0 pmol/mg protein for a brain membrane preparation, 2.4 pmol/mg for liver and 0.25 pmol/mg for red blood cell membranes. In earlier work we had shown that calcium uptake by brain mitochondria is inhibited at much lower toxin concentrations than is liver mitochondrial uptake. Both liver and brain mitochondria bind toxin specifically, but the density of 125I-labeled toxin binding sites on brain mitochondrial preparations (3.3 +/- 0.3 pmol/mg) exceeded by a factor of ten the density on liver mitochondrial preparations (0.3 +/- 0.05 pmol/mg). It is also shown that labeled toxin does not cross synaptosomal membranes, suggesting that mitochondria may not be the site of action of the toxin in vivo. We conclude that beta-bungarotoxin is an enzyme which can bind specifically with high affinity to cell membranes."} {"id": "PMID:1276198", "title": "Anti-actomyosin. Influence on adhesive behaviour of eukaryotic cells and of Cuvierian tubules.", "content": "The effect of antisera against chicken gizzard smooth-muscle actomyosin and against pectoralis striated-muscle actomyosin on adhesive behaviour of eukaryotic cells (from sea urchin embryos and from a silicious sponge) and of Cuvierian tubules has been studied. The results with sea urchin cells, which require divalent cations for aggregation, showed that antiserum to chicken gizzard smooth-muscle actomyosin inhibited reaggreagation of trypsin-treated cells better than mechanically dissociated cells, while anti-chicken pectoralis striated-muscle had no effect. Primary reaggreagation of trypsin-dissociated sponge cells, in the presence of calcium and magnesium, is also inhibitable by anti-gizzard smooth-muscle but not by anti-pectoralis straited muscle. Anti-gizzard smooth-muscle had no effect on secondary reaggregation of sponge cells mediated by a soluble aggregation factor. Anti-gizzard smooth-muscle inhibited Cuvierian tubule adhesion.", "contents": "Anti-actomyosin. Influence on adhesive behaviour of eukaryotic cells and of Cuvierian tubules. The effect of antisera against chicken gizzard smooth-muscle actomyosin and against pectoralis striated-muscle actomyosin on adhesive behaviour of eukaryotic cells (from sea urchin embryos and from a silicious sponge) and of Cuvierian tubules has been studied. The results with sea urchin cells, which require divalent cations for aggregation, showed that antiserum to chicken gizzard smooth-muscle actomyosin inhibited reaggreagation of trypsin-treated cells better than mechanically dissociated cells, while anti-chicken pectoralis striated-muscle had no effect. Primary reaggreagation of trypsin-dissociated sponge cells, in the presence of calcium and magnesium, is also inhibitable by anti-gizzard smooth-muscle but not by anti-pectoralis straited muscle. Anti-gizzard smooth-muscle had no effect on secondary reaggregation of sponge cells mediated by a soluble aggregation factor. Anti-gizzard smooth-muscle inhibited Cuvierian tubule adhesion."} {"id": "PMID:1276199", "title": "Testicular chromatin activation in hypophysectomized rats.", "content": "Incorporation of labeled thymidine into testicular DNA of hypophysectomized rats began to increase after the administration of testosterone propionate and choriogenic gonadotrophin. While the thymidine incorporation reached maximum in 4 days, the DNA polymerase activity did not culminate until 8 days after the initiation of hormone treatment. The high molecular weight (6--8 S), presumably cytoplasmic DNA polymerase accounted almost entirely for this increase. Administration of testosterone propionate and chorionic gonadotrophin to hypophysectomized rats results in an increase of testicular RNA polymerase and chromatin templating activity. Chain elongation and initiation studies revealed that the increased templating capacity of androgen-stimulated testicular chromatin was almost entirely caused by the increase in the number of initiation sites. While the nuclear polymerase I responded relatively rapidly to hormone stimulation and reached a prominent maximum in about three days, the activity of polymerase II was more sluggish and not as prominent. The in vivo incorporation of ortho[32P]phosphate into chromosomal phosphoproteins occurred early during the androgen treatment and reached a maximum in about 20 h. The protein phosphokinase activity peaked later, approx. 72 h after the first administration of hormones.", "contents": "Testicular chromatin activation in hypophysectomized rats. Incorporation of labeled thymidine into testicular DNA of hypophysectomized rats began to increase after the administration of testosterone propionate and choriogenic gonadotrophin. While the thymidine incorporation reached maximum in 4 days, the DNA polymerase activity did not culminate until 8 days after the initiation of hormone treatment. The high molecular weight (6--8 S), presumably cytoplasmic DNA polymerase accounted almost entirely for this increase. Administration of testosterone propionate and chorionic gonadotrophin to hypophysectomized rats results in an increase of testicular RNA polymerase and chromatin templating activity. Chain elongation and initiation studies revealed that the increased templating capacity of androgen-stimulated testicular chromatin was almost entirely caused by the increase in the number of initiation sites. While the nuclear polymerase I responded relatively rapidly to hormone stimulation and reached a prominent maximum in about three days, the activity of polymerase II was more sluggish and not as prominent. The in vivo incorporation of ortho[32P]phosphate into chromosomal phosphoproteins occurred early during the androgen treatment and reached a maximum in about 20 h. The protein phosphokinase activity peaked later, approx. 72 h after the first administration of hormones."} {"id": "PMID:1276200", "title": "Increased synthesis of ribonucleic acids in mouse liver after treatment with a nonionic detergent.", "content": "A single injection of Tween 40 (polyoxyethylene(20)sorbitan monohexanoate) in the dose range of 600--800 mg/kg body weight induced an increased short-term labeling especially of poly(A)-containing mRNAs in mouse liver (using either [3H]orotic acid or [32P]orthophosphate as RNA precursors), and apparently increased the turnover rates of both rRNAs and mRNAs in this organ over a period of 24 h. In the early period (4 h) after the injection of Tween 40, there was also a significant increase in the content of 32P-labeled adenylic acid in microsomal poly(A)-mRNA fraction. The activity of DNA-dependent RNA polymerases in the nuclei of treated animals was stimulated up to 60% over that in control nuclei in the same period after detergent injection.", "contents": "Increased synthesis of ribonucleic acids in mouse liver after treatment with a nonionic detergent. A single injection of Tween 40 (polyoxyethylene(20)sorbitan monohexanoate) in the dose range of 600--800 mg/kg body weight induced an increased short-term labeling especially of poly(A)-containing mRNAs in mouse liver (using either [3H]orotic acid or [32P]orthophosphate as RNA precursors), and apparently increased the turnover rates of both rRNAs and mRNAs in this organ over a period of 24 h. In the early period (4 h) after the injection of Tween 40, there was also a significant increase in the content of 32P-labeled adenylic acid in microsomal poly(A)-mRNA fraction. The activity of DNA-dependent RNA polymerases in the nuclei of treated animals was stimulated up to 60% over that in control nuclei in the same period after detergent injection."} {"id": "PMID:1276201", "title": "Defective protein synthesis of S-30 fraction of reticulocytes of anemic b/b rats.", "content": "The preincubated S-30 fraction from reticulocytes of anemic b/b rats is not able to promote the synthesis of proteins in the presence of hemoglobin RNA provided either from the reticulocytes of phenylhydrazine-treated rats or from the reticulocytes of anemic b/b rats. It was observed that poly(U)-directed polyphenylalanine synthesis is negligible in the same system, suggesting the existence of some alteration in regulatory machinery for protein synthesis in the reticulocytes of the anemic b/b rats.", "contents": "Defective protein synthesis of S-30 fraction of reticulocytes of anemic b/b rats. The preincubated S-30 fraction from reticulocytes of anemic b/b rats is not able to promote the synthesis of proteins in the presence of hemoglobin RNA provided either from the reticulocytes of phenylhydrazine-treated rats or from the reticulocytes of anemic b/b rats. It was observed that poly(U)-directed polyphenylalanine synthesis is negligible in the same system, suggesting the existence of some alteration in regulatory machinery for protein synthesis in the reticulocytes of the anemic b/b rats."} {"id": "PMID:1276202", "title": "The binding of poly(rI) - poly(rC) to human fibroblasts and the induction of interferon.", "content": "Human embryonic fibroblasts produce interferon when incubated at 37 degrees C after being treated at 4 degrees C with poly(rI) - poly(rC), either by addition of the double-stranded duplex or by sequential addition of the constitutent single-stranded polynucleotides. Cells which have been incubated with double-stranded poly(rI) - poly(rC) can be prevented from forming interferon by washing the cells with high concentrations of salt, immediately after adsorption of polynucleotides, or by incubation of the cells with single-stranded polynucleotides. The inhibition is probably due to displacement of the inducing molecule from the cell surface. Interferon production by cells treated sequentially with poly(rI) and poly(rC) is not inhibited by either of these treatments and the polynucleotides are not easily displaced from the cell surface.", "contents": "The binding of poly(rI) - poly(rC) to human fibroblasts and the induction of interferon. Human embryonic fibroblasts produce interferon when incubated at 37 degrees C after being treated at 4 degrees C with poly(rI) - poly(rC), either by addition of the double-stranded duplex or by sequential addition of the constitutent single-stranded polynucleotides. Cells which have been incubated with double-stranded poly(rI) - poly(rC) can be prevented from forming interferon by washing the cells with high concentrations of salt, immediately after adsorption of polynucleotides, or by incubation of the cells with single-stranded polynucleotides. The inhibition is probably due to displacement of the inducing molecule from the cell surface. Interferon production by cells treated sequentially with poly(rI) and poly(rC) is not inhibited by either of these treatments and the polynucleotides are not easily displaced from the cell surface."} {"id": "PMID:1276203", "title": "The divergence between human and baboon globin genes.", "content": "Complementary DNA (cDNA) was prepared with viral RNA-directed DNA polymerase from purified baboon globin messenger RNA (mRNA). Homologous and heterologous hybrids between human and baboon mRNAs and cDNAs were compared for extent of hybridisation and thermal stability. Higher mRNA inputs to the hybridizations were required to reach saturation in the heterologous cases. The melting temperature of the heterologous hybrid was 5 degrees C lower than the homologous hybrid. Between these two primates, divergence has occurred in the globin gene to a smaller extent than that possible from third position changes in the coding sequences of the divergence of total DNA. Globin cDNA prepared from baboon will not in general be useful as a probe for human globin mRNA or human globin gene sequences.", "contents": "The divergence between human and baboon globin genes. Complementary DNA (cDNA) was prepared with viral RNA-directed DNA polymerase from purified baboon globin messenger RNA (mRNA). Homologous and heterologous hybrids between human and baboon mRNAs and cDNAs were compared for extent of hybridisation and thermal stability. Higher mRNA inputs to the hybridizations were required to reach saturation in the heterologous cases. The melting temperature of the heterologous hybrid was 5 degrees C lower than the homologous hybrid. Between these two primates, divergence has occurred in the globin gene to a smaller extent than that possible from third position changes in the coding sequences of the divergence of total DNA. Globin cDNA prepared from baboon will not in general be useful as a probe for human globin mRNA or human globin gene sequences."} {"id": "PMID:1276204", "title": "Estradiol-induced synthesis of vitellogenin. I. The isolation of large polysomes from estrogenized rooster liver.", "content": "Conventional procedures for the isolation of polysomes, applied to estrogenized rooster liver, fail to yield polysomes containing 30 or more ribosomes, the size expected for polysomes synthesizing the estradiol-induced protein vitellogenin. A new procedure characterized by early and selective removal of cell components ribonucleases allowed the isolation of polysomes with up to 55 ribosomes. Electron microscopy was used for the determination of polysome size and showed that the large polysomes were not aggregates.", "contents": "Estradiol-induced synthesis of vitellogenin. I. The isolation of large polysomes from estrogenized rooster liver. Conventional procedures for the isolation of polysomes, applied to estrogenized rooster liver, fail to yield polysomes containing 30 or more ribosomes, the size expected for polysomes synthesizing the estradiol-induced protein vitellogenin. A new procedure characterized by early and selective removal of cell components ribonucleases allowed the isolation of polysomes with up to 55 ribosomes. Electron microscopy was used for the determination of polysome size and showed that the large polysomes were not aggregates."} {"id": "PMID:1276206", "title": "DNA-protein cross-linking by ultraviolet radiation in normal human and xeroderma pigmentosum fibroblasts.", "content": "DNA-protein cross-linking by ultraviolet radiation was measured in human fibroblasts by an adaptation of the method of DNA alkaline elution. To measure cross-linking, a controlled frequency of DNA single-strand breaks was introduced by exposing the cells to a low dose of X-ray at 0 degrees C prior to analysis by alkaline elution. The effect of prior exposure of the cells to ultraviolet radiation was to reduce the rate and/or extent of DNA elution from X-irradiated cells. This effect was attributed to DNA-protein cross-linking, since the effect was reversed by treatment of the cell lysates with proteinase-K. Cross-linking in normal human fibroblasts occurred immediately after ultraviolet irradiation, prior to the appearance of DNA single-strand breaks due to excision repair. Upon incubation of normal cells after exposure, to ultraviolet radiation, the cross-linking was partially repaired. In xeroderma pigmentosum cells, cross-links appeared as in normal cells, but there was no repair. Instead, the extent of cross-linking appeared to increase upon incubation after ultraviolet irradiation.", "contents": "DNA-protein cross-linking by ultraviolet radiation in normal human and xeroderma pigmentosum fibroblasts. DNA-protein cross-linking by ultraviolet radiation was measured in human fibroblasts by an adaptation of the method of DNA alkaline elution. To measure cross-linking, a controlled frequency of DNA single-strand breaks was introduced by exposing the cells to a low dose of X-ray at 0 degrees C prior to analysis by alkaline elution. The effect of prior exposure of the cells to ultraviolet radiation was to reduce the rate and/or extent of DNA elution from X-irradiated cells. This effect was attributed to DNA-protein cross-linking, since the effect was reversed by treatment of the cell lysates with proteinase-K. Cross-linking in normal human fibroblasts occurred immediately after ultraviolet irradiation, prior to the appearance of DNA single-strand breaks due to excision repair. Upon incubation of normal cells after exposure, to ultraviolet radiation, the cross-linking was partially repaired. In xeroderma pigmentosum cells, cross-links appeared as in normal cells, but there was no repair. Instead, the extent of cross-linking appeared to increase upon incubation after ultraviolet irradiation."} {"id": "PMID:1276207", "title": "Phosphorylation and dephosphorylation of membrane proteins as a possible mechanism for structural rearrangement of membrane components.", "content": "A correlation was found between dephosphorylation of chicken erythrocyte membrane proteins, aggregation of intramembrane particles, increase in the lipid bilayer phase of the membrane and exposure of membrane phospholipids toward phospholipase A and trinitrobenzene sulfonic acid. Most of the covalently bound phosphate of the membrane proteins turns over and is associated with 5 major bands. It is suggested that phosphorylation and dephosphorylation of these proteins causes changes in their charge and conformation. Such changes might affect the interaction of these proteins with the neighbouring lipids or lipoprotein complexes and results in the aggregation of intramembrane particles and relative increase in the exposed free lipid bilayer phase of the membrane.", "contents": "Phosphorylation and dephosphorylation of membrane proteins as a possible mechanism for structural rearrangement of membrane components. A correlation was found between dephosphorylation of chicken erythrocyte membrane proteins, aggregation of intramembrane particles, increase in the lipid bilayer phase of the membrane and exposure of membrane phospholipids toward phospholipase A and trinitrobenzene sulfonic acid. Most of the covalently bound phosphate of the membrane proteins turns over and is associated with 5 major bands. It is suggested that phosphorylation and dephosphorylation of these proteins causes changes in their charge and conformation. Such changes might affect the interaction of these proteins with the neighbouring lipids or lipoprotein complexes and results in the aggregation of intramembrane particles and relative increase in the exposed free lipid bilayer phase of the membrane."} {"id": "PMID:1276208", "title": "The interaction of secretin with pancreatic membranes.", "content": "1. 125I-labelled secretin bound rapidly and specifically to membranes from cat pancreas. Binding of labelled hormone was competitively inhibited by unlabelled secretin in the same range of concentrations that stimulated pancreatic adenylate cyclase in these membranes. The dissociation constant of the membrane binding sites for unlabelled secretin as evaluated by these displacement experiments was 4.1-10(-9) M and the number of binding sites 1.0 pmol per mg of membrane protein. 2. Studies using different concentrations of [125I]secretin (at a constant ratio of labelled to unlabelled hormone) revealed a similar value of 4-4-10(-9) M for the dissociation constant. 3. Both the association and dissociation rate constants of [125I]secretin binding were temperature sensitive; the dissociation rate constant increased more rapidly with increase in temperature. The ratio k-1/k+1 (at 22 degrees C) gave a dissociation constant of 3.7-10(-9)M which agrees closely with the figure obtained from equilibrium data. These data indicate that 125I-labelled secretin and unlabelled secretin bind to the same binding site on pancreatic membranes, with high affinity. 4. Unlabelled secretin stimulated pancreatic adenylate cyclase with an apparent Km of 8.4-10(-9) M, while [125I]secretin apparently did not stimulate the adenylate cyclase. Together with the binding data this might suggest that different portions of the secretin molecule are responsible for binding and adenylate cyclase activation. 5. Studies on the specificity of [125I]secretin binding carried out with various peptide hormones (glucagon, human gastrin, pancreozymin and caerulein) which are all inefficient in stimulating pancreatic fluid secretin, showed that these hormones have no influence on the binding of [125I]secretin. In contrast, vasoactive intestinal polypeptide, which stimulates pancreatic fluid and bicarbonate secretion, showed a competitive inhibition of secretin binding to the plasma membrane preparation.", "contents": "The interaction of secretin with pancreatic membranes. 1. 125I-labelled secretin bound rapidly and specifically to membranes from cat pancreas. Binding of labelled hormone was competitively inhibited by unlabelled secretin in the same range of concentrations that stimulated pancreatic adenylate cyclase in these membranes. The dissociation constant of the membrane binding sites for unlabelled secretin as evaluated by these displacement experiments was 4.1-10(-9) M and the number of binding sites 1.0 pmol per mg of membrane protein. 2. Studies using different concentrations of [125I]secretin (at a constant ratio of labelled to unlabelled hormone) revealed a similar value of 4-4-10(-9) M for the dissociation constant. 3. Both the association and dissociation rate constants of [125I]secretin binding were temperature sensitive; the dissociation rate constant increased more rapidly with increase in temperature. The ratio k-1/k+1 (at 22 degrees C) gave a dissociation constant of 3.7-10(-9)M which agrees closely with the figure obtained from equilibrium data. These data indicate that 125I-labelled secretin and unlabelled secretin bind to the same binding site on pancreatic membranes, with high affinity. 4. Unlabelled secretin stimulated pancreatic adenylate cyclase with an apparent Km of 8.4-10(-9) M, while [125I]secretin apparently did not stimulate the adenylate cyclase. Together with the binding data this might suggest that different portions of the secretin molecule are responsible for binding and adenylate cyclase activation. 5. Studies on the specificity of [125I]secretin binding carried out with various peptide hormones (glucagon, human gastrin, pancreozymin and caerulein) which are all inefficient in stimulating pancreatic fluid secretin, showed that these hormones have no influence on the binding of [125I]secretin. In contrast, vasoactive intestinal polypeptide, which stimulates pancreatic fluid and bicarbonate secretion, showed a competitive inhibition of secretin binding to the plasma membrane preparation."} {"id": "PMID:1276209", "title": "Defective ion regulation in a class of membrane-excitation mutants in Paramecium.", "content": "The \"paranoiac\" mutants of Paramecium aurelia show prolonged backward swimming in solutions containing Na+, unlike wild-type paramecia, which jerk back and forth in Na+ solutions. The paranoiac mutants in Na+ solutions also show large losses of cellular K+ and large influxes of Na+. Three different paranoiac mutants all show similar defects in ion regulation but to different degrees. Wild-type Paramecium, in contrast, shows no Na+ -dependent loss of cellular K+ and a much smaller Na+ influx. In K+ -containing solutions, there is no difference between wild-type and paranoiac paramecia with respect to their cellular K+ content. The Na+ influx, the K+ loss, and the duration of backward swimming are all proportional to the extracellular Na+ concentration. Electrophysiologically, the backward swimming of the paranoiac mutants corresponds to a prolonged depolarization of the membrane potential, while the backward jerks of wild-type Paramecium correspond to a series of transient depolarizations. We propose that the large Na+ influxes and the large K+ effluxes in paranoiacs occur during the periods of backward swimming, while the membrane is depolarized.", "contents": "Defective ion regulation in a class of membrane-excitation mutants in Paramecium. The \"paranoiac\" mutants of Paramecium aurelia show prolonged backward swimming in solutions containing Na+, unlike wild-type paramecia, which jerk back and forth in Na+ solutions. The paranoiac mutants in Na+ solutions also show large losses of cellular K+ and large influxes of Na+. Three different paranoiac mutants all show similar defects in ion regulation but to different degrees. Wild-type Paramecium, in contrast, shows no Na+ -dependent loss of cellular K+ and a much smaller Na+ influx. In K+ -containing solutions, there is no difference between wild-type and paranoiac paramecia with respect to their cellular K+ content. The Na+ influx, the K+ loss, and the duration of backward swimming are all proportional to the extracellular Na+ concentration. Electrophysiologically, the backward swimming of the paranoiac mutants corresponds to a prolonged depolarization of the membrane potential, while the backward jerks of wild-type Paramecium correspond to a series of transient depolarizations. We propose that the large Na+ influxes and the large K+ effluxes in paranoiacs occur during the periods of backward swimming, while the membrane is depolarized."} {"id": "PMID:1276210", "title": "Permeability properties and intracellular ion concentrations of epithelial cells in rat duodenum.", "content": "Effects of the K+ concentration in the bathing fluid ([K+]l) on the intracellular K+, Na+ and Cl- concentrations ([K+]i [Na+]i and [Cl-]i) as well as on the electrical potential were studied in rat duodenum. Changes in the mucosal K+ concentration ([K+]m), bringing the sum of Na+ and K+ concentrations to 147.2 mM constant, had little effect on the transmural potential difference (PDt), but did induce marked changes in the mucosal membrane potential (Vm). As [K+]m increased, Vm was depolarized gradually and obeyed the Nernst equation for a potassium electrode in the range of [K+]m greater than approx. 60 mM. Experiments of ion analyses were carried out on strips of duodenum to determine the effect of changing the external K+ concentrations on [K+] i, [Na+]i and [Cl-]i. An increase in [K+]o resulted in increases in [K+]i and [Cl-]i and a decrease in [Na+]i, [K+]i approaching its maximum at [K+]o greater than 70 mM. Such changes in [K+]i and [Na+]i seem to correlate quantitatively with the changes in [K+]o and [Na+]o. The values of the ratio of permeability coefficients, Pna+/PK+ were estimated using the Vm values and intracellular ion concentrations measured in these experiments. The results suggested that there appeared a rather abrupt increase in the PNa+/PK+ ratio from 0 to approx. 0.1, as [K+]m decreased.", "contents": "Permeability properties and intracellular ion concentrations of epithelial cells in rat duodenum. Effects of the K+ concentration in the bathing fluid ([K+]l) on the intracellular K+, Na+ and Cl- concentrations ([K+]i [Na+]i and [Cl-]i) as well as on the electrical potential were studied in rat duodenum. Changes in the mucosal K+ concentration ([K+]m), bringing the sum of Na+ and K+ concentrations to 147.2 mM constant, had little effect on the transmural potential difference (PDt), but did induce marked changes in the mucosal membrane potential (Vm). As [K+]m increased, Vm was depolarized gradually and obeyed the Nernst equation for a potassium electrode in the range of [K+]m greater than approx. 60 mM. Experiments of ion analyses were carried out on strips of duodenum to determine the effect of changing the external K+ concentrations on [K+] i, [Na+]i and [Cl-]i. An increase in [K+]o resulted in increases in [K+]i and [Cl-]i and a decrease in [Na+]i, [K+]i approaching its maximum at [K+]o greater than 70 mM. Such changes in [K+]i and [Na+]i seem to correlate quantitatively with the changes in [K+]o and [Na+]o. The values of the ratio of permeability coefficients, Pna+/PK+ were estimated using the Vm values and intracellular ion concentrations measured in these experiments. The results suggested that there appeared a rather abrupt increase in the PNa+/PK+ ratio from 0 to approx. 0.1, as [K+]m decreased."} {"id": "PMID:1276211", "title": "Sugar transport in reversibly hemolyzed avian erythrocytes.", "content": "The technique of reversible hemolysis represents one approach which may be used to study transport regulation in nucleated red cells. After 1 h of incubation at 37 degrees C, 88% of the ghosts regained their permeability barrier to L-glucose. In these ghosts, the carrier-mediated rate of entry of 3-O-methylglucose was more than 10-fold greater than the rate in intact cells. Glyceraldehyde-3-phosphate dehydrogenase prevented ghosts from resealing when it was present at the time of hemolysis. Albumin, lactic dehydrogenase and peroxidase did not have this effect. Sugar transport rate could not be tested in the unsealed ghosts. Two possible mechanisms for the effect of hypotonic hemolysis on sugar transport rate were discussed: (1) altered membrane organization and (2) loss of intracellular compounds which bind to the membrane and inhibit transport in intact cells.", "contents": "Sugar transport in reversibly hemolyzed avian erythrocytes. The technique of reversible hemolysis represents one approach which may be used to study transport regulation in nucleated red cells. After 1 h of incubation at 37 degrees C, 88% of the ghosts regained their permeability barrier to L-glucose. In these ghosts, the carrier-mediated rate of entry of 3-O-methylglucose was more than 10-fold greater than the rate in intact cells. Glyceraldehyde-3-phosphate dehydrogenase prevented ghosts from resealing when it was present at the time of hemolysis. Albumin, lactic dehydrogenase and peroxidase did not have this effect. Sugar transport rate could not be tested in the unsealed ghosts. Two possible mechanisms for the effect of hypotonic hemolysis on sugar transport rate were discussed: (1) altered membrane organization and (2) loss of intracellular compounds which bind to the membrane and inhibit transport in intact cells."} {"id": "PMID:1276212", "title": "An analysis of the adequacy of the asymmetric carrier model for sugar transport.", "content": "In 1972, Lieb, W. R. and Stein, W. D. (Biochim, Biophys. Acta 265, 187-207) in their review of sugar transport in human erythrocytes concluded that the conventional two-state carrier model was inconsistent with the experimental data available at that time. Since then, other papers have appeared which question the validity of the model. In this paper, we give a brief derivation of the equations describing the two-state carrier model, and analyze the predictions of the model in the classical experiments, i.e. zero-trans, infinite-cis, and equilibrium exchange. We show that the estimate of the half saturation constant of 2.8 mM for glucose at the inner face of the human red cell membrane for the infinite-cis procedure reported by Hankin, B.L., Liev, W.R. and Stein, W.D ((1972) Biochim. Biophys. Acta 288, 114-126) is unreliable. We note that all of the other experimental findings are consistent with the asymmetric carrier model.", "contents": "An analysis of the adequacy of the asymmetric carrier model for sugar transport. In 1972, Lieb, W. R. and Stein, W. D. (Biochim, Biophys. Acta 265, 187-207) in their review of sugar transport in human erythrocytes concluded that the conventional two-state carrier model was inconsistent with the experimental data available at that time. Since then, other papers have appeared which question the validity of the model. In this paper, we give a brief derivation of the equations describing the two-state carrier model, and analyze the predictions of the model in the classical experiments, i.e. zero-trans, infinite-cis, and equilibrium exchange. We show that the estimate of the half saturation constant of 2.8 mM for glucose at the inner face of the human red cell membrane for the infinite-cis procedure reported by Hankin, B.L., Liev, W.R. and Stein, W.D ((1972) Biochim. Biophys. Acta 288, 114-126) is unreliable. We note that all of the other experimental findings are consistent with the asymmetric carrier model."} {"id": "PMID:1276213", "title": "Permeability of rabbit polymorphonuclear leukocyte membranes to urea and other nonelectrolytes.", "content": "The diffusional permeability coefficients of rabbit polymorphonuclear leukocyte membranes to urea, methylurea and thiourea have been measured. It was found that the permeability coefficient of these membranes to urea is very low and that thiourea was more permeable than methylurea which was, in turn, more permeable than urea. These results suggest that there is no need to postulate a carrier-mediated mechanism for urea transport across biological membranes and that the concept of \"aqueous pores\" is not a general property of biological membranes but restricted only to certain cases.", "contents": "Permeability of rabbit polymorphonuclear leukocyte membranes to urea and other nonelectrolytes. The diffusional permeability coefficients of rabbit polymorphonuclear leukocyte membranes to urea, methylurea and thiourea have been measured. It was found that the permeability coefficient of these membranes to urea is very low and that thiourea was more permeable than methylurea which was, in turn, more permeable than urea. These results suggest that there is no need to postulate a carrier-mediated mechanism for urea transport across biological membranes and that the concept of \"aqueous pores\" is not a general property of biological membranes but restricted only to certain cases."} {"id": "PMID:1276214", "title": "On the structure of agglutinated sheep red blood cell membranes.", "content": "Specimens of isolated sheep red blood cell membranes are prepared by an agglutination technique in which membranes are stacked in regular arrays. X-ray diffraction patterns are recorded from such specimens which show meridional and equatorial diffraction phenomena. The meridional reflections correspond to single lamellar repeat periods of 160-186 A. It is concluded that two asymmetric membranes are contained in the elementary period. Lipid phases with preferentially oriented hydrocarbon chains are part of the membrane structure. The stacking of the membranes is also demonstrated in the electron microscope. The X-ray scattering curve of intracellular hemoglobin of intact sheep red blood cells is recorded to a spacing of about 8 A-1. The broad diffraction rings of this scattering curve are replaced by a series of rather sharp rings, when the red blood cells are agglutinated and placed in a hypertonic medium. Both the presence of a functioning membrane and the agglutination appear to be essential for the full expression of this phenomenon.", "contents": "On the structure of agglutinated sheep red blood cell membranes. Specimens of isolated sheep red blood cell membranes are prepared by an agglutination technique in which membranes are stacked in regular arrays. X-ray diffraction patterns are recorded from such specimens which show meridional and equatorial diffraction phenomena. The meridional reflections correspond to single lamellar repeat periods of 160-186 A. It is concluded that two asymmetric membranes are contained in the elementary period. Lipid phases with preferentially oriented hydrocarbon chains are part of the membrane structure. The stacking of the membranes is also demonstrated in the electron microscope. The X-ray scattering curve of intracellular hemoglobin of intact sheep red blood cells is recorded to a spacing of about 8 A-1. The broad diffraction rings of this scattering curve are replaced by a series of rather sharp rings, when the red blood cells are agglutinated and placed in a hypertonic medium. Both the presence of a functioning membrane and the agglutination appear to be essential for the full expression of this phenomenon."} {"id": "PMID:1276215", "title": "Detergent extraction of erythrocyte ghosts. Comparison of residues after cholate and Triton X-100 treatments.", "content": "1. Human erythrocyte ghosts were extracted with individual free and conjugated bile salts and, for comparison, with Triton X-100 under conditions approximating to physiological temperature, pH and tonicity. 2. Treatment with cholate, glycocholate, taurocholate, or with Triton X-100 gave lipid-depleted residues. These could still be seen as ghost-like profiles by phase contrast microscopy. Deopxycholate brought about complete membrane dissolutiom. 3. The cholate residue gave a trilamellar image by electron microscopy and in condensed form gave a smaller membrane repeat than untreated membranes. It had a polypeptide composition representing mainly integral proteins. 4. The Triton X-100 residue had a granular profile in the electron microscope and a polypeptide composition largely representing peripheral proteins.", "contents": "Detergent extraction of erythrocyte ghosts. Comparison of residues after cholate and Triton X-100 treatments. 1. Human erythrocyte ghosts were extracted with individual free and conjugated bile salts and, for comparison, with Triton X-100 under conditions approximating to physiological temperature, pH and tonicity. 2. Treatment with cholate, glycocholate, taurocholate, or with Triton X-100 gave lipid-depleted residues. These could still be seen as ghost-like profiles by phase contrast microscopy. Deopxycholate brought about complete membrane dissolutiom. 3. The cholate residue gave a trilamellar image by electron microscopy and in condensed form gave a smaller membrane repeat than untreated membranes. It had a polypeptide composition representing mainly integral proteins. 4. The Triton X-100 residue had a granular profile in the electron microscope and a polypeptide composition largely representing peripheral proteins."} {"id": "PMID:1276216", "title": "Enzymatic and chemical analyses of pig platelet membrane subfractions isolated by zonal centrifugation.", "content": "1. A mixed membrane fraction prepared from pig platelets was subfractionated, using the \"B 14\" zonal rotor, into two distinct subpopulations of membrane vesicles, each associated with a different phosphodiesterase activity. 2. The lighter subfraction (MI) was enriched 7-8 fold with bis-(p-nitrophenyl) phosphate phosphodiesterase activity and the denser subfraction (MII) showed a similar degree of enrichment of 5'dTMP-p-nitrophenyl ester phosphodiesterase activity. 3. Assays for other enzyme activities revealed slight enrichement (approx. 2 fold) of acid phosphatase, 3'-dTMP-p-nitrophenyl ester phosphodiesterase and beta-glucuronidase activities in MI, and beta-galactosidase in MII. Cyclic AMP phosphodiesterase, lactate dehydrogenase and N-acetyl-beta-glucosaminidase showed negligible activity in both MI and MII, and succinate dehydrogenase activity could not be detected in either subfraction. 4. Chemical analyses of the membrane subfractions demonstrated that MI contained approx. twice as much cholesterol, phospholipid, sialic acid and hexosamine per unit weight of protein than MII. These results are consistent with our previously reported observations from surface-labelling experiments, which indicated that MI was derived principally from the platelet surface-exposed membranes and that MII was probably intracellular in origin. 5. Analysis of the membrane polypeptides by sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed the presence of 12-15 components, in each subfraction, in the mol. wt. range 12000-200000, including a prominent band of approx. mol. wt. 46000, which has beeen identified to be actin. Qualitative as well as possible quantitative differences were apparent in that MII contained three components in addition to those present in MI. 6. Analysis of the periodate-Schiff staining components by sodium dodecyl sulphate-polyacrylamide gel electrophoresis demonstrated the presence of 4 major glycoproteins in both subfractions with apparent mol. wt. ranging from approx. 95000 to 150000; in addition two minor components were also present. Further, a very fast-migrating band, which did not stain with Coomassie blue, was observed in both MI and MII and probably represents lipid material.", "contents": "Enzymatic and chemical analyses of pig platelet membrane subfractions isolated by zonal centrifugation. 1. A mixed membrane fraction prepared from pig platelets was subfractionated, using the \"B 14\" zonal rotor, into two distinct subpopulations of membrane vesicles, each associated with a different phosphodiesterase activity. 2. The lighter subfraction (MI) was enriched 7-8 fold with bis-(p-nitrophenyl) phosphate phosphodiesterase activity and the denser subfraction (MII) showed a similar degree of enrichment of 5'dTMP-p-nitrophenyl ester phosphodiesterase activity. 3. Assays for other enzyme activities revealed slight enrichement (approx. 2 fold) of acid phosphatase, 3'-dTMP-p-nitrophenyl ester phosphodiesterase and beta-glucuronidase activities in MI, and beta-galactosidase in MII. Cyclic AMP phosphodiesterase, lactate dehydrogenase and N-acetyl-beta-glucosaminidase showed negligible activity in both MI and MII, and succinate dehydrogenase activity could not be detected in either subfraction. 4. Chemical analyses of the membrane subfractions demonstrated that MI contained approx. twice as much cholesterol, phospholipid, sialic acid and hexosamine per unit weight of protein than MII. These results are consistent with our previously reported observations from surface-labelling experiments, which indicated that MI was derived principally from the platelet surface-exposed membranes and that MII was probably intracellular in origin. 5. Analysis of the membrane polypeptides by sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed the presence of 12-15 components, in each subfraction, in the mol. wt. range 12000-200000, including a prominent band of approx. mol. wt. 46000, which has beeen identified to be actin. Qualitative as well as possible quantitative differences were apparent in that MII contained three components in addition to those present in MI. 6. Analysis of the periodate-Schiff staining components by sodium dodecyl sulphate-polyacrylamide gel electrophoresis demonstrated the presence of 4 major glycoproteins in both subfractions with apparent mol. wt. ranging from approx. 95000 to 150000; in addition two minor components were also present. Further, a very fast-migrating band, which did not stain with Coomassie blue, was observed in both MI and MII and probably represents lipid material."} {"id": "PMID:1276217", "title": "Light scattering and turbidity measurements on lipid vesicles.", "content": "The dynamic behaviour of model membranes in the form of sonicated liposomes in excess water was studied by means of 90 degrees C light scattering and turbidity measurements. Computer calculations based on the Rayleigh-Gans theory of light scattering were used to estimate the average size of lipid vesicles dispersed in water, taking into account the various structures of the vesicles. Normal reversible changes in the scattered light intensity and turbidity with temperature could be accounted for mainly by the changes in the refractive index of the lipid and irreversible anomalous changes were explained on the basis of fusion of smaller aggregated vesicles.", "contents": "Light scattering and turbidity measurements on lipid vesicles. The dynamic behaviour of model membranes in the form of sonicated liposomes in excess water was studied by means of 90 degrees C light scattering and turbidity measurements. Computer calculations based on the Rayleigh-Gans theory of light scattering were used to estimate the average size of lipid vesicles dispersed in water, taking into account the various structures of the vesicles. Normal reversible changes in the scattered light intensity and turbidity with temperature could be accounted for mainly by the changes in the refractive index of the lipid and irreversible anomalous changes were explained on the basis of fusion of smaller aggregated vesicles."} {"id": "PMID:1276219", "title": "Solubilization of the Semliki Forest virus membrane with sodium deoxycholate.", "content": "The effects of increasing concentrations of sodium deoxycholate on Semliki Forest have been studied. Sodium deoxycholate begins to bind to the virus at less than 0.1 mM free equilibrium concentration and causes lysis of the viral membrane at 0.9 +/- 0.1 mM free equilibrium concentration when 2.2 +/- 0.2 - 103 mol of sodium deoxycholate are bound per mol of virus. Liberation of proteins from the membrane begins at 1.5 +/- 0.1 mM sodium deoxycholate and the proteins released are virtually free from phospholipid above 2.0 mM sodium deoxycholate. The overall mechanism of sodium deoxycholate solubilization of the viral membrane resembles that of Triton X-100 and sodium dodecyl sulphate except that with sodium deoxycholate the various stages of membrane disruption occur at about 10-fold higher equilibrium free detergent concentrations. At sodium deoxycholate concentrations higher than 2.3 mM the viral spike glycoproteins can be separated by sucrose gradient centrifugation or gel filtration into constituent polypeptides E1, E2 and E3. E1 carries the haemagglutinating activity of the virus.", "contents": "Solubilization of the Semliki Forest virus membrane with sodium deoxycholate. The effects of increasing concentrations of sodium deoxycholate on Semliki Forest have been studied. Sodium deoxycholate begins to bind to the virus at less than 0.1 mM free equilibrium concentration and causes lysis of the viral membrane at 0.9 +/- 0.1 mM free equilibrium concentration when 2.2 +/- 0.2 - 103 mol of sodium deoxycholate are bound per mol of virus. Liberation of proteins from the membrane begins at 1.5 +/- 0.1 mM sodium deoxycholate and the proteins released are virtually free from phospholipid above 2.0 mM sodium deoxycholate. The overall mechanism of sodium deoxycholate solubilization of the viral membrane resembles that of Triton X-100 and sodium dodecyl sulphate except that with sodium deoxycholate the various stages of membrane disruption occur at about 10-fold higher equilibrium free detergent concentrations. At sodium deoxycholate concentrations higher than 2.3 mM the viral spike glycoproteins can be separated by sucrose gradient centrifugation or gel filtration into constituent polypeptides E1, E2 and E3. E1 carries the haemagglutinating activity of the virus."} {"id": "PMID:1276220", "title": "Possible relationship between membrane proteins and phospholipid asymmetry in the human erythrocyte membrane.", "content": "After incubation of human erythrocytes at 37 degrees C in the absence of glucose (A) for 24 h, (B) for 4 h with 8 mM hexanol or (C) for 3 h with SH reagents, phosphatidylethanolamine becomes partly susceptible to hydrolysis by phospholipase A2 from Naja naja. The presence of glucose during the pretreatments suppresses this effect, except in the case of SH reagents that inhibit glycolysis. After incubation with tetrathionate, up to 45% of the phosphatidylethanolamine is degraded by the enzyme, an amount considerably in excess of the 20% attacked in fresh erythrocytes. Pancreatic phospholipase A2, an enzyme unable to hydrolyse the phospholipids of intact erythrocytes, partially degrades phosphatidylcholine and phosphatidylethanolamine of erythrocytes pretreated with hexanol or SH reagents. Reagents capable of oxidizing SH groups to disulfides (tetrathionate, o-iodosobenzoate and hydroquinone) even render susceptible to pancreatic phospholipase A2 phosphatidylserine, a phospholipid supposed to be entirely located in the inner lipid layer of the membrane. Alkylating or acylating SH reagents have no such effect. It is postulated that disulfide bond formation between membrane protein SH groups leads to an alteration in protein-phospholipid interactions and consequently induces a reorientation of phospholipids between the inner and the outer membrane lipid layer.", "contents": "Possible relationship between membrane proteins and phospholipid asymmetry in the human erythrocyte membrane. After incubation of human erythrocytes at 37 degrees C in the absence of glucose (A) for 24 h, (B) for 4 h with 8 mM hexanol or (C) for 3 h with SH reagents, phosphatidylethanolamine becomes partly susceptible to hydrolysis by phospholipase A2 from Naja naja. The presence of glucose during the pretreatments suppresses this effect, except in the case of SH reagents that inhibit glycolysis. After incubation with tetrathionate, up to 45% of the phosphatidylethanolamine is degraded by the enzyme, an amount considerably in excess of the 20% attacked in fresh erythrocytes. Pancreatic phospholipase A2, an enzyme unable to hydrolyse the phospholipids of intact erythrocytes, partially degrades phosphatidylcholine and phosphatidylethanolamine of erythrocytes pretreated with hexanol or SH reagents. Reagents capable of oxidizing SH groups to disulfides (tetrathionate, o-iodosobenzoate and hydroquinone) even render susceptible to pancreatic phospholipase A2 phosphatidylserine, a phospholipid supposed to be entirely located in the inner lipid layer of the membrane. Alkylating or acylating SH reagents have no such effect. It is postulated that disulfide bond formation between membrane protein SH groups leads to an alteration in protein-phospholipid interactions and consequently induces a reorientation of phospholipids between the inner and the outer membrane lipid layer."} {"id": "PMID:1276221", "title": "The fusion of abnormal plasma lipoprotein (LP-X) and the erythrocyte membrane in patients with cholestasis studied by electronmicroscopy.", "content": "Adhesion followed by fusion of LP-X vesicles with the erythrocyte membrane is an important contribution to the erythrocyte enlargement in patients with intra or extra hepatic cholestasis. Adhesion of LP-X vesicles is demonstrated by thin section and freeze-etch electronmicroscopy. Fusion of LP-X with the erythrocyte membrane is deduced from biochemical data and freeze-etch electronmicroscopy in that the uptake of cholesterol and lecithin coincides with the increase in smooth areas on the fracture faces of the erythrocyte membrane.", "contents": "The fusion of abnormal plasma lipoprotein (LP-X) and the erythrocyte membrane in patients with cholestasis studied by electronmicroscopy. Adhesion followed by fusion of LP-X vesicles with the erythrocyte membrane is an important contribution to the erythrocyte enlargement in patients with intra or extra hepatic cholestasis. Adhesion of LP-X vesicles is demonstrated by thin section and freeze-etch electronmicroscopy. Fusion of LP-X with the erythrocyte membrane is deduced from biochemical data and freeze-etch electronmicroscopy in that the uptake of cholesterol and lecithin coincides with the increase in smooth areas on the fracture faces of the erythrocyte membrane."} {"id": "PMID:1276222", "title": "Characterization of the membrane matrix derived from the microsomal fraction of rat hepatocytes.", "content": "A highly purified membrane preparation derived from the microsomal fraction of rat hepatocytes has been chemically characterized and fractionated by means of gel filtration. The preparation has been freed of ribosomes and intravesicular protein and has a composition on a w/w basis of 52.1% protein, 45.0% phospholipid, 2.9% carbohydrate and no RNA. 97 +/- 2% of the total membrane phosphorus is accounted for as phospholipid phosphorus. Determination of the molecular weight distribution of the constituent polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave values ranging from 171 000 to 16 000 for the major classes of proteins. Although several membrane glycoproteins have been indentified, the most prominent species has an apparent molecular weight of 171 000, 40% of the total microsomal protein is present in the 49 000-60 000 molecular weight region. Examination of the intrinsic polypeptide composition of membranes obtained from smooth and degranulated rough endoplasmic reticulum revealed no detectable qualitative differences. Sodium dodecyl sulfate-solubilized microsomal membrane proteins were separated by gel filtration into much simplified molecular weight classes, some of which showed predominantly a single electrophoretic component. Amino acid analysis of individual fractions showed a noticeable trend toward a decreasing ratio of acidic to basic residues with decreasing molecular weight. Membrane phosphorus was distributed between two chromatographic fractions: one containing membrane phospholipid (97% of the total) as well as essentially all the cholesterol, the other, at the inclusion volume of the gel filtration system, containing small molecular weight species (3% of the total phosphorus). The absence of a ribonuclease-resistant RNA component eluting near the void volume clearly distinguishes the microsomal membrane from the nuclear envelope.", "contents": "Characterization of the membrane matrix derived from the microsomal fraction of rat hepatocytes. A highly purified membrane preparation derived from the microsomal fraction of rat hepatocytes has been chemically characterized and fractionated by means of gel filtration. The preparation has been freed of ribosomes and intravesicular protein and has a composition on a w/w basis of 52.1% protein, 45.0% phospholipid, 2.9% carbohydrate and no RNA. 97 +/- 2% of the total membrane phosphorus is accounted for as phospholipid phosphorus. Determination of the molecular weight distribution of the constituent polypeptides by sodium dodecyl sulfate-polyacrylamide gel electrophoresis gave values ranging from 171 000 to 16 000 for the major classes of proteins. Although several membrane glycoproteins have been indentified, the most prominent species has an apparent molecular weight of 171 000, 40% of the total microsomal protein is present in the 49 000-60 000 molecular weight region. Examination of the intrinsic polypeptide composition of membranes obtained from smooth and degranulated rough endoplasmic reticulum revealed no detectable qualitative differences. Sodium dodecyl sulfate-solubilized microsomal membrane proteins were separated by gel filtration into much simplified molecular weight classes, some of which showed predominantly a single electrophoretic component. Amino acid analysis of individual fractions showed a noticeable trend toward a decreasing ratio of acidic to basic residues with decreasing molecular weight. Membrane phosphorus was distributed between two chromatographic fractions: one containing membrane phospholipid (97% of the total) as well as essentially all the cholesterol, the other, at the inclusion volume of the gel filtration system, containing small molecular weight species (3% of the total phosphorus). The absence of a ribonuclease-resistant RNA component eluting near the void volume clearly distinguishes the microsomal membrane from the nuclear envelope."} {"id": "PMID:1276223", "title": "Thiamine transport in thiamine-deficient rats. Role of the unstirred water layer.", "content": "As part of a systematic study of alcoholism and thiamine absorption, the effect of diet-induced thiamine deficiency and the role of the unstirred water layer on the thiamine transport were investigated. Using 3H-labeled dextran as a marker of adherent mucosal volume, jejunal uptake of 14C-labeled thiamine hydrochloride was measured, in vitro, in thiamine-deficient rats and pair-fed controls. Uptake of low thiamine concentrations (0.2 and 0.5 muM) was greater in the thiamine-deficient rats than in the controls. In contrast, uptake rates for high thiamine concentrations (20 and 50 muM) were similar in both groups. While Jmax was unaltered, Km was decreased in thiamine deficiency, suggesting a decrease in unstirred water layer thickness. Accordingly, the thickness of the water layer was measured in both groups of animals and correlated with Jmax and Km under unstirred and stirred conditions. Without stirring, there was no difference in Jmax between the two groups. In contrast, both Km and the water layer were reduced in the thiamine-deficient rats. With stirring, Jmax was not affected, but both Km and the water layer thickness were reduced to similar values in both groups. Reversal of thiamine deficiency resulted in the return of thiamine uptake and the unstirred water layer thickness to control values. These data support the concept of a dual system of thiamine transport and emphasize the role of the unstirred water layer as an important determinant of transport kinetics not only under physiologic situations but also in diet-induced rat thiamine deficiency, a model for a clinical patholigical state. The decrease in the unstirred water layer thickness in thiamine deficiency may be also viewed as a possible adaptive mechanism to facilitate absorption of meager supplies of thiamine.", "contents": "Thiamine transport in thiamine-deficient rats. Role of the unstirred water layer. As part of a systematic study of alcoholism and thiamine absorption, the effect of diet-induced thiamine deficiency and the role of the unstirred water layer on the thiamine transport were investigated. Using 3H-labeled dextran as a marker of adherent mucosal volume, jejunal uptake of 14C-labeled thiamine hydrochloride was measured, in vitro, in thiamine-deficient rats and pair-fed controls. Uptake of low thiamine concentrations (0.2 and 0.5 muM) was greater in the thiamine-deficient rats than in the controls. In contrast, uptake rates for high thiamine concentrations (20 and 50 muM) were similar in both groups. While Jmax was unaltered, Km was decreased in thiamine deficiency, suggesting a decrease in unstirred water layer thickness. Accordingly, the thickness of the water layer was measured in both groups of animals and correlated with Jmax and Km under unstirred and stirred conditions. Without stirring, there was no difference in Jmax between the two groups. In contrast, both Km and the water layer were reduced in the thiamine-deficient rats. With stirring, Jmax was not affected, but both Km and the water layer thickness were reduced to similar values in both groups. Reversal of thiamine deficiency resulted in the return of thiamine uptake and the unstirred water layer thickness to control values. These data support the concept of a dual system of thiamine transport and emphasize the role of the unstirred water layer as an important determinant of transport kinetics not only under physiologic situations but also in diet-induced rat thiamine deficiency, a model for a clinical patholigical state. The decrease in the unstirred water layer thickness in thiamine deficiency may be also viewed as a possible adaptive mechanism to facilitate absorption of meager supplies of thiamine."} {"id": "PMID:1276224", "title": "Enzyme loading of electrically homogeneous human red blood cell ghosts prepared by dielelctric breakdown.", "content": "Human red blood cell ghosts were prepared by electrical haemolysis at 0 degrees C in isotonic solutions using a discharge chamber which was part of a high voltage circuit. The size distribution of the ghosts was normally distributed, the modal (=mean) volume was approx. 115 mum3, performing the electrical haemolysis in the following solution: 105 mM KCI, 20 mM NaCL, 4mM MgCl2, 7.6 mM Na2HPO4, 2.94 mM NaH2PO4, 10 mM glucose, pH 7.2. Resealing was carried out at o degrees C for 10 min (after the haemolytic step) and then for further 20 min at 37 degrees C. The mean volume of the ghost preparation could be changed by variation of the phosphate concentration in the above solution replacing a part of NaCl by phosphate (5 mM phosphate: 94 mum3, 15 mM phosphate: 135 mum3). The breakdown voltage of the ghost cell membranes measured with a hydrodynamic focusing Coulter Counter depends on the mean volume (94 mum3 = 1.04 V, 134 mum3 = 1.36 V). On the other hand, the breakdown voltage is constant throughout each size distribution pointing to an \"electrically homogeneous\" ghost preparation. The sensitiviity of the Coulter Counter to detect electrical inhomogeneities in the membranes of a ghost population is demonstrated by dielectric breakdown measurements of an apparently normally distributed ghost preparation containing two different \"electrically homogeneous\" ghost population i.e. with two different breakdown voltages. The ghost cells obtained by electrical haemolysis in the above solution containing 10mM phosphate were fairly impermeable to sucrose and behave like an ideal osometer. It is further demonstrated that ghost cells can be loaded with enzymes (e.g. urease) and drugs using this technique and that these loaded ghost cells can be used as bioactive capsules for clinical application.", "contents": "Enzyme loading of electrically homogeneous human red blood cell ghosts prepared by dielelctric breakdown. Human red blood cell ghosts were prepared by electrical haemolysis at 0 degrees C in isotonic solutions using a discharge chamber which was part of a high voltage circuit. The size distribution of the ghosts was normally distributed, the modal (=mean) volume was approx. 115 mum3, performing the electrical haemolysis in the following solution: 105 mM KCI, 20 mM NaCL, 4mM MgCl2, 7.6 mM Na2HPO4, 2.94 mM NaH2PO4, 10 mM glucose, pH 7.2. Resealing was carried out at o degrees C for 10 min (after the haemolytic step) and then for further 20 min at 37 degrees C. The mean volume of the ghost preparation could be changed by variation of the phosphate concentration in the above solution replacing a part of NaCl by phosphate (5 mM phosphate: 94 mum3, 15 mM phosphate: 135 mum3). The breakdown voltage of the ghost cell membranes measured with a hydrodynamic focusing Coulter Counter depends on the mean volume (94 mum3 = 1.04 V, 134 mum3 = 1.36 V). On the other hand, the breakdown voltage is constant throughout each size distribution pointing to an \"electrically homogeneous\" ghost preparation. The sensitiviity of the Coulter Counter to detect electrical inhomogeneities in the membranes of a ghost population is demonstrated by dielectric breakdown measurements of an apparently normally distributed ghost preparation containing two different \"electrically homogeneous\" ghost population i.e. with two different breakdown voltages. The ghost cells obtained by electrical haemolysis in the above solution containing 10mM phosphate were fairly impermeable to sucrose and behave like an ideal osometer. It is further demonstrated that ghost cells can be loaded with enzymes (e.g. urease) and drugs using this technique and that these loaded ghost cells can be used as bioactive capsules for clinical application."} {"id": "PMID:1276225", "title": "Monitoring membrane potentials in Ehrlich ascites tumor cells by means of a fluorescent dye.", "content": "1. The fluorescent intensity of the dye 3,3'-dipropylthiodicarbocyanine iodide was measured in suspensions of Ehrlich ascites tumor cells in an attempt to monitor their membrane potentials under a variety of different ionic and metabolic conditions. 2. In the presence of valinomycin, fluorescent intensity is dependent on log [K+]medium (the fluorescent intensity increased with increasing [K+]medium) where K+ replaced Na+ in the medium. Cellular K+ content also influenced fluorescent intensity in the presence of valinomycin. With lower cellular K+, fluorescent intensity in the presence of valinomycin for any given concentration was increased. 3. In the presence of gramicidin fluorescent intensity was highest in Krebs-Ringer and decreased with the substitution of choline+ for Na+. 4. The observations with ionophores are consistent with the hypothesis that the dye monitors membrane potential in these cells with an increase in fluorescence indicating membrane depolarization (internal becomes more positive). 5. The estimated membrane potentials were influenced by the way in which the cells were treated. Upon dilution of the cells from 1 in 20 to 1 in 300 the initial estimations were between -50 and -60 mV. With incubation at 1 in 300 dilution for 1 h at room temperature or a 37 degrees C, the membrane potentials ranged from -18 to -42 mV. 6. Estimations of membrane potential on the basis of chloride distribution (Cl-cell/Cl-medium) in equilibrated cells ranged from -13 to -32 mV. 7. Addition of glucose to cells equilibrated at 37 degrees C for 30 min in the presence of rotenone led to a decrease in fluorescent intensity indicating hyperpolarization. Addition of ouabain in turn led to a 70 to 100% reversal of fluorescent intensity. This hyperpolarization is therefore probably due to the electrogenic activity of the sodium pump. 8. The addition of amino acids known to require external Na+ for transport increased fluorescent intensity (depolarization) reaching a maximum at higher concentrations of amino acids. Plots of 1/deltafluorescence vs. 1/[glycine] were linear with an apparent Km of 2-3 mM. The increase in fluorescence with amino acids always required external Na+. Plots of 1/fluorescence vs. 1/[Na+]medium were also linear with an apparent Km of 29 mM. These apparent Km values compare favorably with those derived from amino acid transport studies using tracers. These data indicate that the Na+-dependent transport of amino acids in these cells is electrogenic.", "contents": "Monitoring membrane potentials in Ehrlich ascites tumor cells by means of a fluorescent dye. 1. The fluorescent intensity of the dye 3,3'-dipropylthiodicarbocyanine iodide was measured in suspensions of Ehrlich ascites tumor cells in an attempt to monitor their membrane potentials under a variety of different ionic and metabolic conditions. 2. In the presence of valinomycin, fluorescent intensity is dependent on log [K+]medium (the fluorescent intensity increased with increasing [K+]medium) where K+ replaced Na+ in the medium. Cellular K+ content also influenced fluorescent intensity in the presence of valinomycin. With lower cellular K+, fluorescent intensity in the presence of valinomycin for any given concentration was increased. 3. In the presence of gramicidin fluorescent intensity was highest in Krebs-Ringer and decreased with the substitution of choline+ for Na+. 4. The observations with ionophores are consistent with the hypothesis that the dye monitors membrane potential in these cells with an increase in fluorescence indicating membrane depolarization (internal becomes more positive). 5. The estimated membrane potentials were influenced by the way in which the cells were treated. Upon dilution of the cells from 1 in 20 to 1 in 300 the initial estimations were between -50 and -60 mV. With incubation at 1 in 300 dilution for 1 h at room temperature or a 37 degrees C, the membrane potentials ranged from -18 to -42 mV. 6. Estimations of membrane potential on the basis of chloride distribution (Cl-cell/Cl-medium) in equilibrated cells ranged from -13 to -32 mV. 7. Addition of glucose to cells equilibrated at 37 degrees C for 30 min in the presence of rotenone led to a decrease in fluorescent intensity indicating hyperpolarization. Addition of ouabain in turn led to a 70 to 100% reversal of fluorescent intensity. This hyperpolarization is therefore probably due to the electrogenic activity of the sodium pump. 8. The addition of amino acids known to require external Na+ for transport increased fluorescent intensity (depolarization) reaching a maximum at higher concentrations of amino acids. Plots of 1/deltafluorescence vs. 1/[glycine] were linear with an apparent Km of 2-3 mM. The increase in fluorescence with amino acids always required external Na+. Plots of 1/fluorescence vs. 1/[Na+]medium were also linear with an apparent Km of 29 mM. These apparent Km values compare favorably with those derived from amino acid transport studies using tracers. These data indicate that the Na+-dependent transport of amino acids in these cells is electrogenic."} {"id": "PMID:1276226", "title": "Modulation of 2,3-diphosphoglycerate 31P-NMR resonance positions by red cell membrane shape.", "content": "Na+ transport in the red cells of the dog is dependent on cell volume, a 20% change in cell volume leading to a 25-fold increase in apparent Na+ flux; the effect is dependent upon metabolic energy. We have found that swelling and shrinking dog red cells causes a shift in the 31P-NMR peak of 2,3-diphosphoglycerate, which is present in dog red cells at 5.5 mM. Control experiments indicate that the 2,3-diphosphoglycerate resonance peak shifts may not be attributed to: interaction with hemoglobin, changes in cell pH, ionic strength, diamagnetic susceptibility or small changes in the Mg2+/2,3-diphosphoglycerate ratio. Experiments with chlorpromazine and pentanol which alter red cell membrane area by a mechanism different from osmotic swelling suggest that 2,3-diphosphoglycerate interacts with a binding site in the cell that is dependent upon the physical condition of the dog red cell membrane.", "contents": "Modulation of 2,3-diphosphoglycerate 31P-NMR resonance positions by red cell membrane shape. Na+ transport in the red cells of the dog is dependent on cell volume, a 20% change in cell volume leading to a 25-fold increase in apparent Na+ flux; the effect is dependent upon metabolic energy. We have found that swelling and shrinking dog red cells causes a shift in the 31P-NMR peak of 2,3-diphosphoglycerate, which is present in dog red cells at 5.5 mM. Control experiments indicate that the 2,3-diphosphoglycerate resonance peak shifts may not be attributed to: interaction with hemoglobin, changes in cell pH, ionic strength, diamagnetic susceptibility or small changes in the Mg2+/2,3-diphosphoglycerate ratio. Experiments with chlorpromazine and pentanol which alter red cell membrane area by a mechanism different from osmotic swelling suggest that 2,3-diphosphoglycerate interacts with a binding site in the cell that is dependent upon the physical condition of the dog red cell membrane."} {"id": "PMID:1276227", "title": "Carbodiimide-intermediated esterification of the inorganic phosphates and the effect of tertiary amine base.", "content": "Detailed analysis of appropriate 31P nuclear-magnetic-resonance spectra shows that under the usual laboratory conditions, carbodiimide-induced condensation of orthophosphoric acid in a number of solvents leads to condensation only slightly beyond the metaphosphate composition in the presence of strong tertiary amines; whereas in the absence of amine, the condensation proceeds into the ultraphosphate region about halfway between the metaphosphate and phosphoric anhydride compositions. With amine, the principal product consists of the cyclic trimetaphosphate anion, with one of the nonbridging oxygen atoms substituted by the urea resulting from hydration of the carboiimide, i.e., (O2-) P-O-P(O2-) -O-P(O) [N[CH(CH3)2] see article [C(O)NHCH(CH3)2]] for the condensation with diisopropylcarbodiimide. Without amine, the major product is the 1,5-mu-oxotetrametaphosphate anion see article. The well-known carbodiimide-mediated phosphorylation of alcohols with orthophosphoric acid is shown to be directly attributable to the high reactivity of the phosphate branch groups of the carbodiimide-generated ultraphosphates.", "contents": "Carbodiimide-intermediated esterification of the inorganic phosphates and the effect of tertiary amine base. Detailed analysis of appropriate 31P nuclear-magnetic-resonance spectra shows that under the usual laboratory conditions, carbodiimide-induced condensation of orthophosphoric acid in a number of solvents leads to condensation only slightly beyond the metaphosphate composition in the presence of strong tertiary amines; whereas in the absence of amine, the condensation proceeds into the ultraphosphate region about halfway between the metaphosphate and phosphoric anhydride compositions. With amine, the principal product consists of the cyclic trimetaphosphate anion, with one of the nonbridging oxygen atoms substituted by the urea resulting from hydration of the carboiimide, i.e., (O2-) P-O-P(O2-) -O-P(O) [N[CH(CH3)2] see article [C(O)NHCH(CH3)2]] for the condensation with diisopropylcarbodiimide. Without amine, the major product is the 1,5-mu-oxotetrametaphosphate anion see article. The well-known carbodiimide-mediated phosphorylation of alcohols with orthophosphoric acid is shown to be directly attributable to the high reactivity of the phosphate branch groups of the carbodiimide-generated ultraphosphates."} {"id": "PMID:1276228", "title": "Micellar catalysis of the alkylation of mercuric ions by alkyl cobalt(III) complexes.", "content": "Anionic micelles of sodium lauryl sulfate, NaLS, catalyze the monoalkylation of Hg2+ in dilute acid by alkyl aquobis-(dimethyl glyoximato) cobalt (III), RCo(DH)2(H2O) degrees and the related propane derivatives RCo(DOH) DOpn (H2O)+, where R = Me, Et, n-C5H11. Nonionic micelles of Igepal do not catalyze the reaction. In the absence of micelles RCo(DH)2(H2O) degrees is considerably more reactive than RCo(DOH)DOpn(H2O)+, but this higher reactivity is offset in part by its higher basicity. Anionic micelles markedly increase the basicity of RCo(DOH)DOpn(H2O)+ and slightly increase that of RCo(DH)2(H2O) degrees. For reactions of the unprotonated Co(III) complexes the maximum rate enhancements by micelles of NaLS are: R = Me, 19(131); Et, 58 (65); n-C5H11, 46 (32). (The values in parentheses are for RCo(DOH)DOpn(H2O)+.)", "contents": "Micellar catalysis of the alkylation of mercuric ions by alkyl cobalt(III) complexes. Anionic micelles of sodium lauryl sulfate, NaLS, catalyze the monoalkylation of Hg2+ in dilute acid by alkyl aquobis-(dimethyl glyoximato) cobalt (III), RCo(DH)2(H2O) degrees and the related propane derivatives RCo(DOH) DOpn (H2O)+, where R = Me, Et, n-C5H11. Nonionic micelles of Igepal do not catalyze the reaction. In the absence of micelles RCo(DH)2(H2O) degrees is considerably more reactive than RCo(DOH)DOpn(H2O)+, but this higher reactivity is offset in part by its higher basicity. Anionic micelles markedly increase the basicity of RCo(DOH)DOpn(H2O)+ and slightly increase that of RCo(DH)2(H2O) degrees. For reactions of the unprotonated Co(III) complexes the maximum rate enhancements by micelles of NaLS are: R = Me, 19(131); Et, 58 (65); n-C5H11, 46 (32). (The values in parentheses are for RCo(DOH)DOpn(H2O)+.)"} {"id": "PMID:1276230", "title": "Stereoselective binding of copper(II), zinc(II), cobalt(II), and ni(II) to the optically active amino acids beta-(2-pyridyl)-alpha-alanine and beta-(6-methyl-2-pyridyl)-alpha-alanine, analogs of histidine and phenylalanine.", "content": "In order to study the metal ion binding of optically active beta-(2-pyridyl)-alpha-alanine, NH2CH(CH2C5H4N)CO2H, Pyala, and beta-(6-methyl-2-pyridyl)-alpha-alanine, NH2CH(CH2C5H3NCH3)CO2H, Mepyala, these pyridine analogs of histidine were synthesized and resolved; absolute configurations were determined for the isolated enatiomers. Protonation constants and formation constants for the binding of L-Pyala, D,L-Pyala, D-Mepyala, and D,L-Mepyala with Cu(II), Ni(II), Co(II), and Zn(II) were determined by potentiometrictitration. They show that the formation constant (Kx) for the reaction, M(L-Pyala) + D-Pyala in equilibrium M(L-Pyala)(D-pyala), is larger (up to 8.7 times larger) than that (K2) for the coordination of the same enantiomer, M(L-Pyala) + L-Pyala in equilibrium M(L-Pyala)2. Although the difference between Kx and K2 can be explained on a statistical basis for Cu(II), the larger differences for Ni(II), Co(II), and Zn(II) demonstrate that their M(L-Pyala)complexes bind D-Pyala more favorably than they do L-Pyala. A similar trend was found for the optical isomers of Mepyala except that the stereoselectivity is less than in the Pyala system. This presumably results from the reduced coordinating ability of the 6-methylpyridyl group as compared to the less crowded pyridyl donor. Using ideas previously applied to the analogous histidine system, the observed stereoselectivities may be explained in terms of the structures of the complexes.", "contents": "Stereoselective binding of copper(II), zinc(II), cobalt(II), and ni(II) to the optically active amino acids beta-(2-pyridyl)-alpha-alanine and beta-(6-methyl-2-pyridyl)-alpha-alanine, analogs of histidine and phenylalanine. In order to study the metal ion binding of optically active beta-(2-pyridyl)-alpha-alanine, NH2CH(CH2C5H4N)CO2H, Pyala, and beta-(6-methyl-2-pyridyl)-alpha-alanine, NH2CH(CH2C5H3NCH3)CO2H, Mepyala, these pyridine analogs of histidine were synthesized and resolved; absolute configurations were determined for the isolated enatiomers. Protonation constants and formation constants for the binding of L-Pyala, D,L-Pyala, D-Mepyala, and D,L-Mepyala with Cu(II), Ni(II), Co(II), and Zn(II) were determined by potentiometrictitration. They show that the formation constant (Kx) for the reaction, M(L-Pyala) + D-Pyala in equilibrium M(L-Pyala)(D-pyala), is larger (up to 8.7 times larger) than that (K2) for the coordination of the same enantiomer, M(L-Pyala) + L-Pyala in equilibrium M(L-Pyala)2. Although the difference between Kx and K2 can be explained on a statistical basis for Cu(II), the larger differences for Ni(II), Co(II), and Zn(II) demonstrate that their M(L-Pyala)complexes bind D-Pyala more favorably than they do L-Pyala. A similar trend was found for the optical isomers of Mepyala except that the stereoselectivity is less than in the Pyala system. This presumably results from the reduced coordinating ability of the 6-methylpyridyl group as compared to the less crowded pyridyl donor. Using ideas previously applied to the analogous histidine system, the observed stereoselectivities may be explained in terms of the structures of the complexes."} {"id": "PMID:1276231", "title": "The reactions of oxo-osmium ligand complexes with isopentenyl adenine and its nucleoside.", "content": "We report syntheses of oxo-osmium(VI)bis(ligand) esters of N6-(delta2-isopentenyl) adenine (6-ipAde) and its nucleoside (IPA) which result from the addition of OsO4 to the double bond of the isopentenyl group. A study of the kinetics of these reactions shows that under typical conditions the rates of reaction relative to thymidine are as follows: for OsO4-pyridine: thymidine = 1; 6-ipAde = 4600: for OsO4-2,2'-bipyridyl: thymidine = 380; 6-ipAde = 8600; IPA = 8600. We also report syntheses of osmate esters of IPA in which the osmium is bonded through the 2'-and 3'-hydroxyl groups of the ribose residue.", "contents": "The reactions of oxo-osmium ligand complexes with isopentenyl adenine and its nucleoside. We report syntheses of oxo-osmium(VI)bis(ligand) esters of N6-(delta2-isopentenyl) adenine (6-ipAde) and its nucleoside (IPA) which result from the addition of OsO4 to the double bond of the isopentenyl group. A study of the kinetics of these reactions shows that under typical conditions the rates of reaction relative to thymidine are as follows: for OsO4-pyridine: thymidine = 1; 6-ipAde = 4600: for OsO4-2,2'-bipyridyl: thymidine = 380; 6-ipAde = 8600; IPA = 8600. We also report syntheses of osmate esters of IPA in which the osmium is bonded through the 2'-and 3'-hydroxyl groups of the ribose residue."} {"id": "PMID:1276232", "title": "Carbon-13 magnetic resonance spectra of nucleosides and their Pd(II) complexes.", "content": "Chemical shifts occurring in carbon-13 magnetic resonance spectroscopy are utilized to assess the site of complexation of nucleosides to enPdC12 in neutral aqueous solutions. Binding occurs at N3 in cytidine, thymidine, and uridien, at N7 in 1-methylguanosine, and at N1 in guanosine. For most carbon atoms adjacent to N3 in the pyrimidine nucleosides the complexation shifts of the basic ligand are about 30% of the corresponding upfield protonation shifts. All complexes are of the form enPdL2 indicating that the ligands are unidentate and that the tendency to chelation is weak. Carbon-13 magnetic resonance spectroscopy appears to be the best method for delineating these complexes in solution. Due to the high avidity of chloride ion for Pt(II), cis dichloro Pd(II) complexes may be better models for intracellular action of the corresponding Pt(II) complexes than the Pt(II) complexes themselves.", "contents": "Carbon-13 magnetic resonance spectra of nucleosides and their Pd(II) complexes. Chemical shifts occurring in carbon-13 magnetic resonance spectroscopy are utilized to assess the site of complexation of nucleosides to enPdC12 in neutral aqueous solutions. Binding occurs at N3 in cytidine, thymidine, and uridien, at N7 in 1-methylguanosine, and at N1 in guanosine. For most carbon atoms adjacent to N3 in the pyrimidine nucleosides the complexation shifts of the basic ligand are about 30% of the corresponding upfield protonation shifts. All complexes are of the form enPdL2 indicating that the ligands are unidentate and that the tendency to chelation is weak. Carbon-13 magnetic resonance spectroscopy appears to be the best method for delineating these complexes in solution. Due to the high avidity of chloride ion for Pt(II), cis dichloro Pd(II) complexes may be better models for intracellular action of the corresponding Pt(II) complexes than the Pt(II) complexes themselves."} {"id": "PMID:1276234", "title": "Interaction of copper(II) with the fungal metabolite, citrinin.", "content": "Copper(II) reacts with citrinin to form 1:1 and 1:2 chelates. The formation constants of these copper(II) chelates have been determined in the solvent 50% (v/v) dioxane-water. Citrinin in the solid state is a p-quinone methide. It may exist as an equilibrium mixture of the p-quinone and o-quinone methides in solution. The experimental evidence indicates that upon chelate formation it exists predominantly in the o-quinone form.", "contents": "Interaction of copper(II) with the fungal metabolite, citrinin. Copper(II) reacts with citrinin to form 1:1 and 1:2 chelates. The formation constants of these copper(II) chelates have been determined in the solvent 50% (v/v) dioxane-water. Citrinin in the solid state is a p-quinone methide. It may exist as an equilibrium mixture of the p-quinone and o-quinone methides in solution. The experimental evidence indicates that upon chelate formation it exists predominantly in the o-quinone form."} {"id": "PMID:1276235", "title": "[Phenylalanyl-tRNA synthetase of wheat embryos. Purification, molecular weight, structure, properties].", "content": "From wheat germ, a phenylalanyl-tRNA synthetase (E.C.6.1.1.20) has been isolated and purified 187 fold by means of ammonium sulfate fractionation (40-50 per cent) followed by Sephadex G-200 gel filtration, chromatographies on DEAE-cellulose and hydroxyapatite. The enzyme appears to be homogeneous on Sephadex G-200 molecular filtration and polyacrylamide gel electrophoresis. Molecular weight determinations by sucrose gradient centrifugation, gel filtration and gel electrophoresis give an average of 250 00 daltons. The enzyme is dissociated in 1 per cent sodium dodecyl sulfate into two different equimolar components of 80 000 and 50 000 daltons ; this result suggests that the phenylalanyl-tRNA synthetase has a subunit structure : alpha2 beta2. Dissociation with sodium dodecyl sulfate and dithiothreitol gives four other components, probably resulting from the breakdown of the subunits. Optima values of pH, Mg2+ and K+ concentrations, effect of SH-compnents, kinetic parameters have been determined in the aminoacylation reaction. Physical and catalytic properties of wheat germ phenylalanyl-tRNA synthetase appear very similar to those of the yeast and E. coli enzymes.", "contents": "[Phenylalanyl-tRNA synthetase of wheat embryos. Purification, molecular weight, structure, properties]. From wheat germ, a phenylalanyl-tRNA synthetase (E.C.6.1.1.20) has been isolated and purified 187 fold by means of ammonium sulfate fractionation (40-50 per cent) followed by Sephadex G-200 gel filtration, chromatographies on DEAE-cellulose and hydroxyapatite. The enzyme appears to be homogeneous on Sephadex G-200 molecular filtration and polyacrylamide gel electrophoresis. Molecular weight determinations by sucrose gradient centrifugation, gel filtration and gel electrophoresis give an average of 250 00 daltons. The enzyme is dissociated in 1 per cent sodium dodecyl sulfate into two different equimolar components of 80 000 and 50 000 daltons ; this result suggests that the phenylalanyl-tRNA synthetase has a subunit structure : alpha2 beta2. Dissociation with sodium dodecyl sulfate and dithiothreitol gives four other components, probably resulting from the breakdown of the subunits. Optima values of pH, Mg2+ and K+ concentrations, effect of SH-compnents, kinetic parameters have been determined in the aminoacylation reaction. Physical and catalytic properties of wheat germ phenylalanyl-tRNA synthetase appear very similar to those of the yeast and E. coli enzymes."} {"id": "PMID:1276236", "title": "[Perparation and comparative analytical study of cat liver microsomes].", "content": "Cat liver homogenates have been fractionated by differential centrifugation. Four particulate fractions (1 000 X g, 10 000 X g, and 145 000 X g) and a supernatant have been obtained. The biochemical composition of these fractions has been established from the assay and distribution pattern of 22 enzymatic and chemical constituents including marker enzymes for mitochondria, lysosomes, peroxisomes, plasma membranes, endoplasmic reticulum, Golgi apparatus and cell sap. The microsomal fraction was characterized by a moderate contamination with large cytoplasmic granules and by a low yield in protein and cholesterol. It contained 50 per cent of Golgi complex and about 40 per cent of plasma membranes. Morphological analysis of subcellular fractions was performed and confirmed biochemical results.", "contents": "[Perparation and comparative analytical study of cat liver microsomes]. Cat liver homogenates have been fractionated by differential centrifugation. Four particulate fractions (1 000 X g, 10 000 X g, and 145 000 X g) and a supernatant have been obtained. The biochemical composition of these fractions has been established from the assay and distribution pattern of 22 enzymatic and chemical constituents including marker enzymes for mitochondria, lysosomes, peroxisomes, plasma membranes, endoplasmic reticulum, Golgi apparatus and cell sap. The microsomal fraction was characterized by a moderate contamination with large cytoplasmic granules and by a low yield in protein and cholesterol. It contained 50 per cent of Golgi complex and about 40 per cent of plasma membranes. Morphological analysis of subcellular fractions was performed and confirmed biochemical results."} {"id": "PMID:1276237", "title": "[Properties of histones on hydrophobic chromatography].", "content": "The hydrophobic chromatography on alkylated Sepharose allows to separate the histones into three groups which exhibit an increasing affinity for the support HI less than H2A-H2B less than H3-H4. In this fractionation procedure, the behaviour of the histones taken separately or pair-associated, is discussed in relation with the ability of these proteins to complex each other in vitro and in vivo.", "contents": "[Properties of histones on hydrophobic chromatography]. The hydrophobic chromatography on alkylated Sepharose allows to separate the histones into three groups which exhibit an increasing affinity for the support HI less than H2A-H2B less than H3-H4. In this fractionation procedure, the behaviour of the histones taken separately or pair-associated, is discussed in relation with the ability of these proteins to complex each other in vitro and in vivo."} {"id": "PMID:1276238", "title": "A comparative study by sucrose gradient electrophoresis of messenger ribonucleoprotein complexes.", "content": "The recently developed method of sucrose gradient electrophoresis has been used in the investigation of mRNA containing particles prepared in an undenatured state. The particles containing messenger RNA migrate as a homogeneous fraction with a mobility different from that of ribosomal praticles. Informosomes and polysomal mRNPs have about the same mobility. On the contrary artificial complexes, formed by the reaction of cytoplasmic binding factor with RNA, migrate as a heterogeneous fraction. The particles carrying mRNA are drastically and irreversibly affected by a treatment with EDTA. Sodium deoxycholate removes some proteins but seems also to denature them. After treatment by high salt or Sodium deoxycholate the mRNPs migrate as a homogeneous fraction showing that all particles are equally affected.", "contents": "A comparative study by sucrose gradient electrophoresis of messenger ribonucleoprotein complexes. The recently developed method of sucrose gradient electrophoresis has been used in the investigation of mRNA containing particles prepared in an undenatured state. The particles containing messenger RNA migrate as a homogeneous fraction with a mobility different from that of ribosomal praticles. Informosomes and polysomal mRNPs have about the same mobility. On the contrary artificial complexes, formed by the reaction of cytoplasmic binding factor with RNA, migrate as a heterogeneous fraction. The particles carrying mRNA are drastically and irreversibly affected by a treatment with EDTA. Sodium deoxycholate removes some proteins but seems also to denature them. After treatment by high salt or Sodium deoxycholate the mRNPs migrate as a homogeneous fraction showing that all particles are equally affected."} {"id": "PMID:1276239", "title": "[Demonstration of 2 phosphate transport systems in Candida tropicalis].", "content": "Candida tropicalis has two phosphate transport systems, one of which is constitutive and has a low affinity for its substrate (Kmapp 1.2.10(-3) M). The other one characterized by a high affinity for H2PO4- (Kmapp = 4.5.10(-6) M) appears only under phosphate starvation conditions. The regulation of the latter would act on the one hand on the synthesis of binding proteins for P1 (repression-derepression) and on the other on the activation or inactivation of the carriers.", "contents": "[Demonstration of 2 phosphate transport systems in Candida tropicalis]. Candida tropicalis has two phosphate transport systems, one of which is constitutive and has a low affinity for its substrate (Kmapp 1.2.10(-3) M). The other one characterized by a high affinity for H2PO4- (Kmapp = 4.5.10(-6) M) appears only under phosphate starvation conditions. The regulation of the latter would act on the one hand on the synthesis of binding proteins for P1 (repression-derepression) and on the other on the activation or inactivation of the carriers."} {"id": "PMID:1276240", "title": "[In vivo metabolism of rat submaxillary gland phospholipids].", "content": "The metabolism of the phospholipids of the submaxillary gland are studied after intraperitoneal injections of [32P]-orthophosphate in several groups of rats. The gland contains mainly phosphatidylcholines and phosphatidylethanolamines and in smaller quantities phosphatidylinositols, phosphatidylserines, sphingomyelins, polyglycerophosphatides, lysophosphatidylcholines and phosphatidic acids. The specific activities of the phospholipids measured in relation to the time (1/2 hour, 1, 2 and 3 hours) show a strong incorporation in the phosphatidylinositols then in the phosphatidylcholines. The other phospholipids have lower activities. The specific activities of the phospholipids measured one hour after injection of different pharmacodynamic agents show the phosphatidylinositols, phosphatidylcholines, sphingomyelins and lysophosphatidylcholines are altered. Acetylcholine increases their turnover, Atropine reduces it, and the addition of atropine counteracts the effect of acetylcholine in all these phospholipids.", "contents": "[In vivo metabolism of rat submaxillary gland phospholipids]. The metabolism of the phospholipids of the submaxillary gland are studied after intraperitoneal injections of [32P]-orthophosphate in several groups of rats. The gland contains mainly phosphatidylcholines and phosphatidylethanolamines and in smaller quantities phosphatidylinositols, phosphatidylserines, sphingomyelins, polyglycerophosphatides, lysophosphatidylcholines and phosphatidic acids. The specific activities of the phospholipids measured in relation to the time (1/2 hour, 1, 2 and 3 hours) show a strong incorporation in the phosphatidylinositols then in the phosphatidylcholines. The other phospholipids have lower activities. The specific activities of the phospholipids measured one hour after injection of different pharmacodynamic agents show the phosphatidylinositols, phosphatidylcholines, sphingomyelins and lysophosphatidylcholines are altered. Acetylcholine increases their turnover, Atropine reduces it, and the addition of atropine counteracts the effect of acetylcholine in all these phospholipids."} {"id": "PMID:1276252", "title": "[The mechanism of action of the deoxyribonuclease of rat liver chromatin on DNA].", "content": "A mechanism of action of DNAase, isolated by chromatin extraction with 0.4 M NaCl, on DNA is described. The enzyme is an endonuclease, it does not require the presence of double-stranded regions in the DNA molecule, does not distinct single-stranded breaks in DNA, and it preferably attacks single-stranded DNA. It hydrolyses DNA for 3'-phosphodiester bonds to octane nucleotides which are resistant to the enzyme activity. The action of the enzyme on DNA does not depend on the position of terminal phosphates. Chromatin DNAase is not specific to DNAs from different origins.", "contents": "[The mechanism of action of the deoxyribonuclease of rat liver chromatin on DNA]. A mechanism of action of DNAase, isolated by chromatin extraction with 0.4 M NaCl, on DNA is described. The enzyme is an endonuclease, it does not require the presence of double-stranded regions in the DNA molecule, does not distinct single-stranded breaks in DNA, and it preferably attacks single-stranded DNA. It hydrolyses DNA for 3'-phosphodiester bonds to octane nucleotides which are resistant to the enzyme activity. The action of the enzyme on DNA does not depend on the position of terminal phosphates. Chromatin DNAase is not specific to DNAs from different origins."} {"id": "PMID:1276253", "title": "[Comparison of the properties of L-threonine dehydratase isolated from the livers of intact, adrenalectomized or cortisol-treated rats].", "content": "L-Threonine dehydratase preparations were isolated from liver of intact, treated with hydrocortisone and adrenalectomized rats. These preparations had different properties in stability, sensitivity to proteases and kinetic patterns. The preparations possessed also serine dehydratase activity, and the ratio threonine: serine activities was modified during the procedure of enzyme purification. It appears that the hormones affect not only the amount of enzyme proteins, but the qualitative properties of these proteins.", "contents": "[Comparison of the properties of L-threonine dehydratase isolated from the livers of intact, adrenalectomized or cortisol-treated rats]. L-Threonine dehydratase preparations were isolated from liver of intact, treated with hydrocortisone and adrenalectomized rats. These preparations had different properties in stability, sensitivity to proteases and kinetic patterns. The preparations possessed also serine dehydratase activity, and the ratio threonine: serine activities was modified during the procedure of enzyme purification. It appears that the hormones affect not only the amount of enzyme proteins, but the qualitative properties of these proteins."} {"id": "PMID:1276254", "title": "[The effect of polyene antibiotics on fractions of DNP both bound and not bound to dog kidney nuclear membranes].", "content": "Effects of amphotericine B and nistatine on nuclear membrane-bound DNP (DNPm) and free DNP (DNPf) from dog kidney are studied. Intravenous injection of amphotericine B resulted in the increase of binding of DNP particles with nuclear membrane: the content of DNA in DNPm fraction was 50-fold increased. The injection of nistatine did not affect DNP binding with nuclear membrane. Amphotericine B alone increased the protein-DNA ratio and decreased the RNA/DNA ratio in DNPf fraction. Both amphotericine B and nistatine sharply increased the protein/DNA ratio and practically did not change the RNA/DNA ratio in DNPm fraction. Amphotericine B produced considerable changes in temperature denaturation of DNA in DNPo, while nistatine produced no effect. Both antibiotics considerably changed the composition of acid soluble proteins in DNPm and DNPf, non-histone proteins in DNPf, and also they caused the changed and quantitative redistribution of separate lipid components in DNPm lipids. Polyene antibiotics are suggested to effect on animal cell nuclear structures.", "contents": "[The effect of polyene antibiotics on fractions of DNP both bound and not bound to dog kidney nuclear membranes]. Effects of amphotericine B and nistatine on nuclear membrane-bound DNP (DNPm) and free DNP (DNPf) from dog kidney are studied. Intravenous injection of amphotericine B resulted in the increase of binding of DNP particles with nuclear membrane: the content of DNA in DNPm fraction was 50-fold increased. The injection of nistatine did not affect DNP binding with nuclear membrane. Amphotericine B alone increased the protein-DNA ratio and decreased the RNA/DNA ratio in DNPf fraction. Both amphotericine B and nistatine sharply increased the protein/DNA ratio and practically did not change the RNA/DNA ratio in DNPm fraction. Amphotericine B produced considerable changes in temperature denaturation of DNA in DNPo, while nistatine produced no effect. Both antibiotics considerably changed the composition of acid soluble proteins in DNPm and DNPf, non-histone proteins in DNPf, and also they caused the changed and quantitative redistribution of separate lipid components in DNPm lipids. Polyene antibiotics are suggested to effect on animal cell nuclear structures."} {"id": "PMID:1276255", "title": "[Manganese content in chlorophyll-protein complexes of higher plants].", "content": "The incorporation of manganese in pigment-protein lamellae complexes was studied. Manganese content was estimated by radioisotopic technique after the precipitation by ammonium sulfate, gel filtration, and polyacrylamide gel electrophoresis of isolated complexes. None of isolated complexes showed manganese content more than 10(-10) g/mg of protein. Possible reason of such a low manganese binding in pigment-protein complexes is discussed.", "contents": "[Manganese content in chlorophyll-protein complexes of higher plants]. The incorporation of manganese in pigment-protein lamellae complexes was studied. Manganese content was estimated by radioisotopic technique after the precipitation by ammonium sulfate, gel filtration, and polyacrylamide gel electrophoresis of isolated complexes. None of isolated complexes showed manganese content more than 10(-10) g/mg of protein. Possible reason of such a low manganese binding in pigment-protein complexes is discussed."} {"id": "PMID:1276256", "title": "[The role of ribosomal proteins in in vitro ribosome-membrane interactions].", "content": "The in vitro binding of total ribosomal proteins with rough endoplasmic membranes, from which 70% of ribosomes are eliminated by EDTA (ME) is studied. It is found that in conditions of specific interaction of ribosomes with membranes about 75% of total ribosomal proteins are bound with ME. Membranes, heterogenous in their content (different protein/lipid ratio), became homogenous in their buyoant density after the binding with proteins. The ability of membrane-ribosomal protein complex to bind ribosomes is not decreased, as it can be expected, but is considerablly increased, thus indicating on a non-specific character of ribosome binding. Ribosomal subunits lacking about half of structural protein are capable to bind with ribosome-binding membrane receptors and with some additional sites. This binding is also non-specific, because the binding efficiency of large and small subunits is the same.", "contents": "[The role of ribosomal proteins in in vitro ribosome-membrane interactions]. The in vitro binding of total ribosomal proteins with rough endoplasmic membranes, from which 70% of ribosomes are eliminated by EDTA (ME) is studied. It is found that in conditions of specific interaction of ribosomes with membranes about 75% of total ribosomal proteins are bound with ME. Membranes, heterogenous in their content (different protein/lipid ratio), became homogenous in their buyoant density after the binding with proteins. The ability of membrane-ribosomal protein complex to bind ribosomes is not decreased, as it can be expected, but is considerablly increased, thus indicating on a non-specific character of ribosome binding. Ribosomal subunits lacking about half of structural protein are capable to bind with ribosome-binding membrane receptors and with some additional sites. This binding is also non-specific, because the binding efficiency of large and small subunits is the same."} {"id": "PMID:1276257", "title": "[Use of differences in substrate inhibition for determination of the interrelationship between molar fractions of lactate dehydrogenase subunits].", "content": "A kinetic method of estimating the ratio of mole quota of H and M human lactate dehydrogenase (LDG) subunits is proposed, based on changes in substrate inhibition of LDG isoenzymes with lactate. Stability of kinetic constants for a long period of time is demonstrated. The dependency of activities ratio under low and high substrate concentration on the contribution of mole quota of LDG M subunits is studied. The correlation of experimental and theoretical values is shown to be: r=0.998 p less than 0.001. A comparison is carried out of the content of LDG subunits molar quotas in artificial mixtures with electrophoretic experimental data, a good coinsidence of these values being registered. The informative importance of the method described with standard methods of the estimation of LDG isoenzyme systems is discussed. No effect of components of human diploid cells homogenate and an insignificant effect of blood serum components on kinetic constants of LDG isoenzymes is registered. A dependency of variation coefficients on the enzyme activity is studied, minimal omegan value being 0.6%. The applicability of the method described for the calculation of quantitative content of both LDG subunits in natural objects (blood serum, diploid cell homogenate etc.) is demonstrated.", "contents": "[Use of differences in substrate inhibition for determination of the interrelationship between molar fractions of lactate dehydrogenase subunits]. A kinetic method of estimating the ratio of mole quota of H and M human lactate dehydrogenase (LDG) subunits is proposed, based on changes in substrate inhibition of LDG isoenzymes with lactate. Stability of kinetic constants for a long period of time is demonstrated. The dependency of activities ratio under low and high substrate concentration on the contribution of mole quota of LDG M subunits is studied. The correlation of experimental and theoretical values is shown to be: r=0.998 p less than 0.001. A comparison is carried out of the content of LDG subunits molar quotas in artificial mixtures with electrophoretic experimental data, a good coinsidence of these values being registered. The informative importance of the method described with standard methods of the estimation of LDG isoenzyme systems is discussed. No effect of components of human diploid cells homogenate and an insignificant effect of blood serum components on kinetic constants of LDG isoenzymes is registered. A dependency of variation coefficients on the enzyme activity is studied, minimal omegan value being 0.6%. The applicability of the method described for the calculation of quantitative content of both LDG subunits in natural objects (blood serum, diploid cell homogenate etc.) is demonstrated."} {"id": "PMID:1276258", "title": "[Structure and protein composition of the bacteriophage T2L connector].", "content": "Methods of isolating structural bacteriophage T2 fragments containing: 1. a fragment consisting of a connector, tail tube and contracted sheath; 2. a fragment consisting of a free head, a connector and contracted sheath; 3. a fraction of some free tail tube and some free connectors; 4. a fraction of some free tail, free connectors and free fibers. The following parameters of connector consisting from a neck and a sleeve, which in its turn consists of a cap and a leg, are determined by means of electrone microscopy: 1) the length and the diameter of a cap and a sleeve being 45 and 145 A respectively; 2) the length and the diameter of a sleeve leg being 45 and 85 A respectively; 3) the length and the diameter of a connector neck being 85 and 70 A respectively. Polyacrylamide gel electrophoresis revealed in connectors proteins having molecular weight of 14 000, 15 000, 26 000 and 35 000 daltons.", "contents": "[Structure and protein composition of the bacteriophage T2L connector]. Methods of isolating structural bacteriophage T2 fragments containing: 1. a fragment consisting of a connector, tail tube and contracted sheath; 2. a fragment consisting of a free head, a connector and contracted sheath; 3. a fraction of some free tail tube and some free connectors; 4. a fraction of some free tail, free connectors and free fibers. The following parameters of connector consisting from a neck and a sleeve, which in its turn consists of a cap and a leg, are determined by means of electrone microscopy: 1) the length and the diameter of a cap and a sleeve being 45 and 145 A respectively; 2) the length and the diameter of a sleeve leg being 45 and 85 A respectively; 3) the length and the diameter of a connector neck being 85 and 70 A respectively. Polyacrylamide gel electrophoresis revealed in connectors proteins having molecular weight of 14 000, 15 000, 26 000 and 35 000 daltons."} {"id": "PMID:1276259", "title": "[Study of carnosine complexes with nucleotides by the method of high resolution nuclear magnetic resonance].", "content": "It is shown that the formation of a carnosine--nucleotide complex (ATP, ADP, AMP) takes place. The stability of the complex mainly depends on: 1) the staking interaction between the heterocyclic rings of carnosine and nucleotides; 2) the electrostatic interaction between the phosphate groups of nucleotide and the positive charged amino group NH3+ of the beta-alanine part of carnosine. The formation of the hydrogen bond between dipeptide COO- group and N1 or N7 of nucleotide is also possible. The complex stability strongly depends on the charge-state of the components and little on the number of the phosphate groups of nucleotide (ATP greater than or equal to ADP greater than AMP).", "contents": "[Study of carnosine complexes with nucleotides by the method of high resolution nuclear magnetic resonance]. It is shown that the formation of a carnosine--nucleotide complex (ATP, ADP, AMP) takes place. The stability of the complex mainly depends on: 1) the staking interaction between the heterocyclic rings of carnosine and nucleotides; 2) the electrostatic interaction between the phosphate groups of nucleotide and the positive charged amino group NH3+ of the beta-alanine part of carnosine. The formation of the hydrogen bond between dipeptide COO- group and N1 or N7 of nucleotide is also possible. The complex stability strongly depends on the charge-state of the components and little on the number of the phosphate groups of nucleotide (ATP greater than or equal to ADP greater than AMP)."} {"id": "PMID:1276261", "title": "[Preparative isolation and study of the reassociation kinetics of a T2 phage DNA fraction containing readily melting regions].", "content": "A DNA fraction comprising 6% of total DNA and containing readily-melting regions is isolated from phage T2 DNA using preparative chromatography on MAK columns at T congruent to T m--3 degrees C. Two denaturation regions, differing in the stability for 7 degrees, were observed on this DNA melting curve. A sharp increase of the reassociation rate at initial moments under reassociation temperatures T r approximately less than m --25 degrees C was observed. Thermodynamic characteristics obtained under the repeated melting of DNA fragments after reassociation confirm the fact, that under these reassociation temperatures the incorporation of readily-melting regions into spiral duplexes takes place.", "contents": "[Preparative isolation and study of the reassociation kinetics of a T2 phage DNA fraction containing readily melting regions]. A DNA fraction comprising 6% of total DNA and containing readily-melting regions is isolated from phage T2 DNA using preparative chromatography on MAK columns at T congruent to T m--3 degrees C. Two denaturation regions, differing in the stability for 7 degrees, were observed on this DNA melting curve. A sharp increase of the reassociation rate at initial moments under reassociation temperatures T r approximately less than m --25 degrees C was observed. Thermodynamic characteristics obtained under the repeated melting of DNA fragments after reassociation confirm the fact, that under these reassociation temperatures the incorporation of readily-melting regions into spiral duplexes takes place."} {"id": "PMID:1276262", "title": "[Isolation of RNA containing a polyadenylic acid sequence by chromatography on unmodified cellulose].", "content": "A new modification of the procedure of the isolation of polyA-containing RNAs is worked out, which makes possible to isolate this RNA fraction free of considerable contamination with rRNA. The administration of 0.0001 M EDTA-Na2 provides the absence of RNA aggregation and prevents non-specific RNA binding on cellulose columns, which takes place when more high EDTA-Na2 concentrations in elution solutions are applied. Under these conditions synthetic polyA in model experiments practically completely binds with cellulose in a broad range of concentrations. It permits to use the procedure described for the preparative isolation of RNA fractions, containing polyA sequences.", "contents": "[Isolation of RNA containing a polyadenylic acid sequence by chromatography on unmodified cellulose]. A new modification of the procedure of the isolation of polyA-containing RNAs is worked out, which makes possible to isolate this RNA fraction free of considerable contamination with rRNA. The administration of 0.0001 M EDTA-Na2 provides the absence of RNA aggregation and prevents non-specific RNA binding on cellulose columns, which takes place when more high EDTA-Na2 concentrations in elution solutions are applied. Under these conditions synthetic polyA in model experiments practically completely binds with cellulose in a broad range of concentrations. It permits to use the procedure described for the preparative isolation of RNA fractions, containing polyA sequences."} {"id": "PMID:1276263", "title": "[Electrophoresis and electrofocusing of rhodopsin solubilized by triton X-100].", "content": "Detergent-rhodopsin micells (component I) were separated from other fast and slow migrating protein components under electrophoresis of triton X-100 solubilized bovine rod outer segments (ROS). Treatment of ROS by alum caused a complete disappearance of non-rhodopsin proteins and the appearance of slow migrating band (component II). Preliminary bleaching of dark extracts did not affect the migration rate of the component I. The addition of urea to solubilizing mixture caused the increase of component I content and the diffusity components I and II bands. The rate of electrophoretic migration and the content of components I and II sharply decreased together with the appearance of fast migrating pink-brown band after the addition of 2-mercaptoethanol. The extracts from alum-treated ROS were separated into 15-20 protein bands under acrylamide gel isoelectric focusing. Such protein heterogeneity probably depended on the ability of triton X-100 to form micells with different isoelectric points during the interaction with ampholines in the electric field. These micells, having different isoelectric points, are shown to contain one and the same protein--opsin.", "contents": "[Electrophoresis and electrofocusing of rhodopsin solubilized by triton X-100]. Detergent-rhodopsin micells (component I) were separated from other fast and slow migrating protein components under electrophoresis of triton X-100 solubilized bovine rod outer segments (ROS). Treatment of ROS by alum caused a complete disappearance of non-rhodopsin proteins and the appearance of slow migrating band (component II). Preliminary bleaching of dark extracts did not affect the migration rate of the component I. The addition of urea to solubilizing mixture caused the increase of component I content and the diffusity components I and II bands. The rate of electrophoretic migration and the content of components I and II sharply decreased together with the appearance of fast migrating pink-brown band after the addition of 2-mercaptoethanol. The extracts from alum-treated ROS were separated into 15-20 protein bands under acrylamide gel isoelectric focusing. Such protein heterogeneity probably depended on the ability of triton X-100 to form micells with different isoelectric points during the interaction with ampholines in the electric field. These micells, having different isoelectric points, are shown to contain one and the same protein--opsin."} {"id": "PMID:1276264", "title": "[Chlorophyll a and b biosynthesis in the dark in etiolated leaves infiltrated by exogenous chlorophyllide a].", "content": "Exogenous chlorophyllide a was introduced into etiolated rye leaves by the vacuum-infiltration technique. Appearance and accumulation of chlorophylls a and b within the leaves are observed during continued darkening, protochlorophyllide photoreduction being avoided. The pigments are identified by the solubility in petroleum ether, paper chromatograms, the fluorescence maxima, the peculiarities of exciting light 430 and 460 nm effects on fluorescence intensity, the specific interaction with hydrochloric hydroxylamine. The conclusion is made that before illumination etioplasts already contain enzyme systems and substrates which provide esterification of chlorophyllide a to chlorophyll a and conversion of chlorophyll a into chlorophyll b.", "contents": "[Chlorophyll a and b biosynthesis in the dark in etiolated leaves infiltrated by exogenous chlorophyllide a]. Exogenous chlorophyllide a was introduced into etiolated rye leaves by the vacuum-infiltration technique. Appearance and accumulation of chlorophylls a and b within the leaves are observed during continued darkening, protochlorophyllide photoreduction being avoided. The pigments are identified by the solubility in petroleum ether, paper chromatograms, the fluorescence maxima, the peculiarities of exciting light 430 and 460 nm effects on fluorescence intensity, the specific interaction with hydrochloric hydroxylamine. The conclusion is made that before illumination etioplasts already contain enzyme systems and substrates which provide esterification of chlorophyllide a to chlorophyll a and conversion of chlorophyll a into chlorophyll b."} {"id": "PMID:1276265", "title": "[Photochemical properties of fucoxanthine].", "content": "The ability of fucoxantine for photooxidation by oxygen in a number of organic solvents and for photoreduction by oxorbic acid and phenylhydrazine in pyridine is demonstrated. The reactions are irreversible under common conditions. At the same time fucoxanthine possesses a pronounced ability for photosensitization of red-ox reaction between methyl red and ascorbic acid or phenylhydrazine, which suggests a formation of reversible very labile intermediate pigment compounds at initial steps of photoreaction.", "contents": "[Photochemical properties of fucoxanthine]. The ability of fucoxantine for photooxidation by oxygen in a number of organic solvents and for photoreduction by oxorbic acid and phenylhydrazine in pyridine is demonstrated. The reactions are irreversible under common conditions. At the same time fucoxanthine possesses a pronounced ability for photosensitization of red-ox reaction between methyl red and ascorbic acid or phenylhydrazine, which suggests a formation of reversible very labile intermediate pigment compounds at initial steps of photoreaction."} {"id": "PMID:1276266", "title": "[Rat liver methylation of nuclear DNA following hydrocortisone induction].", "content": "After intravenous hydrocortisone injection (2 mg per 100 g of animal weight) DNA methylase activity in rat liver increases 1.5-2 times. Rat liver DNA is capable of being methylated in vitro by homologous and heterologous (from rat spleen and ascite carcinoma cells) enzymes. Rat liver DNA isolated 40 min after hydrocortisone injection contains 1.5 times more 5-methylcytosine and is able to accept 1.5 times less methyl groups from (3H-methyl)-S-adenosylmethionine in the in vitro methylation reaction by enzymes from rat spleen as compared to liver DNA isolated from nontreated rats. Thus, there is DNA supermethylation in rat liver cells occurring under the action of the hormone. This induced change in the methylation level of DNA in rat liver is reversible: 6 hours after a single hydrocortisone injection the amount of 5-methylcytosine in DNA decreases to normal, and the DNA ability to accept methyl groups in the in vitro methylation is the same as compared to that of liver DNA from control animals. The induced reversible DNA methylation is to be considered as a mechanism for the regulation of DNA transcription and cell genetic activity.", "contents": "[Rat liver methylation of nuclear DNA following hydrocortisone induction]. After intravenous hydrocortisone injection (2 mg per 100 g of animal weight) DNA methylase activity in rat liver increases 1.5-2 times. Rat liver DNA is capable of being methylated in vitro by homologous and heterologous (from rat spleen and ascite carcinoma cells) enzymes. Rat liver DNA isolated 40 min after hydrocortisone injection contains 1.5 times more 5-methylcytosine and is able to accept 1.5 times less methyl groups from (3H-methyl)-S-adenosylmethionine in the in vitro methylation reaction by enzymes from rat spleen as compared to liver DNA isolated from nontreated rats. Thus, there is DNA supermethylation in rat liver cells occurring under the action of the hormone. This induced change in the methylation level of DNA in rat liver is reversible: 6 hours after a single hydrocortisone injection the amount of 5-methylcytosine in DNA decreases to normal, and the DNA ability to accept methyl groups in the in vitro methylation is the same as compared to that of liver DNA from control animals. The induced reversible DNA methylation is to be considered as a mechanism for the regulation of DNA transcription and cell genetic activity."} {"id": "PMID:1276267", "title": "[Isolation of phospholipase D from cotton seeds].", "content": "A method of isolating homogenous phospholipase D from cotton seeds is described. The homogeneity of the enzyme preparation is demonstrated by means of polyacrylamide disc electrophoresis, gel filtration through Sephadex G-200 and determination of N-terminal amino acid residue, which turned to be glutamic acid. Molecular weight of the enzyme is found to be 71000 +/- 3000. Several equilibrium forms of the enzyme are observed.", "contents": "[Isolation of phospholipase D from cotton seeds]. A method of isolating homogenous phospholipase D from cotton seeds is described. The homogeneity of the enzyme preparation is demonstrated by means of polyacrylamide disc electrophoresis, gel filtration through Sephadex G-200 and determination of N-terminal amino acid residue, which turned to be glutamic acid. Molecular weight of the enzyme is found to be 71000 +/- 3000. Several equilibrium forms of the enzyme are observed."} {"id": "PMID:1276268", "title": "[Preparatory extraction of 5'-oligoribonucleotides using ribonuclease from cobra venom].", "content": "Cobra (Naja oxiana) venom ribonuclease, which catalyses hydrolysis of polyribonucleotides to 5'-oligonucleotides, was used to obtain preparatively isoplit oligonucleotide fractions, containing 2-30 nucleotides. The yield of hydrolysis products varied depending on the degree of hydrolysis. Hydrolysis rates of different polynucleotides were studied. Hydrolysis rate of polyadenylic acid was 20 times as high as that for polyuridylic acid. Quantitative ratios of isoplit fractions did not vary significantly under similar degree of hydrolysis of polyadenylic and polyuridilic acids. Chromatography on QAE-Sepahdex in ammonium bicarbonate concentration gradient containing 15% dioxan was used to separate enzymatic hydrolysates of polynucleotides, which permitted to bring the fraction isolation to simple evaporation.", "contents": "[Preparatory extraction of 5'-oligoribonucleotides using ribonuclease from cobra venom]. Cobra (Naja oxiana) venom ribonuclease, which catalyses hydrolysis of polyribonucleotides to 5'-oligonucleotides, was used to obtain preparatively isoplit oligonucleotide fractions, containing 2-30 nucleotides. The yield of hydrolysis products varied depending on the degree of hydrolysis. Hydrolysis rates of different polynucleotides were studied. Hydrolysis rate of polyadenylic acid was 20 times as high as that for polyuridylic acid. Quantitative ratios of isoplit fractions did not vary significantly under similar degree of hydrolysis of polyadenylic and polyuridilic acids. Chromatography on QAE-Sepahdex in ammonium bicarbonate concentration gradient containing 15% dioxan was used to separate enzymatic hydrolysates of polynucleotides, which permitted to bring the fraction isolation to simple evaporation."} {"id": "PMID:1276269", "title": "[Kinetics of enzymatic hydrolysis of quaternary aminoalkyl esters of aromatic mono- and dicarboxylic acids by butyrylcholinesterase from horse serum].", "content": "Enzymatic hydrolysis kinetics of benzoylcholine (BzCh), phehylpropionic acid choline ester (PK-157), suberic acid dicholine ester (D-6) and p-phenylenediacetic (PK-139), p-phenylenedipropionic (PK-154 and PK-155), p-phenylenediacryc (PK-150 and PK-151) and phtalic (PK-105) acids diaminoalkyl esters by horse blood serum butyrylcholinesterase (BuChE) was studied. Hydrolysis constants Km, V and Kss were estimated by means of different graphic methods. PK-157 ester turned to be highly specific selective substrate for BuChE, its V being 20 times as high and Km -- 20 times as low as those for acetylcholine (ACh). The highest V value was found for D-6 in the case of diesters. Hydrolysis of aromatic dicarbonic acids diesters was characterized with significantly lower V values (0.6-10.% of V for ACh) and extremely low Km values (approximately 10(-5) -- 10(-6) M). Substrate inhibition was observed under the hydrolysis of BzCh, PK-157, D-6 and all aromatic dicarbonic acids esters by BuChE. Formal kinetic analysis revealed that inactive complex, which formed in this case, corresponded to ES2 composition. The appearance of substrate inhibition for BuChE and its increasing are supposed to be due to the increase in the size and in the rigidity of the acyl part of the molecule in the number of substrates studied.", "contents": "[Kinetics of enzymatic hydrolysis of quaternary aminoalkyl esters of aromatic mono- and dicarboxylic acids by butyrylcholinesterase from horse serum]. Enzymatic hydrolysis kinetics of benzoylcholine (BzCh), phehylpropionic acid choline ester (PK-157), suberic acid dicholine ester (D-6) and p-phenylenediacetic (PK-139), p-phenylenedipropionic (PK-154 and PK-155), p-phenylenediacryc (PK-150 and PK-151) and phtalic (PK-105) acids diaminoalkyl esters by horse blood serum butyrylcholinesterase (BuChE) was studied. Hydrolysis constants Km, V and Kss were estimated by means of different graphic methods. PK-157 ester turned to be highly specific selective substrate for BuChE, its V being 20 times as high and Km -- 20 times as low as those for acetylcholine (ACh). The highest V value was found for D-6 in the case of diesters. Hydrolysis of aromatic dicarbonic acids diesters was characterized with significantly lower V values (0.6-10.% of V for ACh) and extremely low Km values (approximately 10(-5) -- 10(-6) M). Substrate inhibition was observed under the hydrolysis of BzCh, PK-157, D-6 and all aromatic dicarbonic acids esters by BuChE. Formal kinetic analysis revealed that inactive complex, which formed in this case, corresponded to ES2 composition. The appearance of substrate inhibition for BuChE and its increasing are supposed to be due to the increase in the size and in the rigidity of the acyl part of the molecule in the number of substrates studied."} {"id": "PMID:1276271", "title": "[The effect of cycloheximide on incorporation of newly formed mRNA into membrane-bound polyribosomes in rat liver cells].", "content": "Incorporation kinetics of new synthesized mRNA into free and endoplasmic membrane-bound polyribosomes in the absence of normal translation (when protein synthesis in inhibited by 98% with cycloheximide) is studied. mRNA is found to incorporate into both free and bound polyribosomes. Relative content of new synthesized membrane-bound polyribosomes in the presence of cycloheximide within 2.5-4.5 hours is by 30-40% lower as compared with the control. This fact can be explained either by the absence of a growing peptide of a sufficient length, which is necessary for the formation of a part of membrane-bound polyribosomes, or by a restricted number of attachment sites on membranes as a result of delayed translation of mRNA in pre-existed polyribosomes. It is suggested that 1) the growing peptide in liver cells is responsible for the recognition of a membrane only under the formation of only one type of membrane-bound polyribosomes, or 2) the formation of all bound polyribosomes has a single mechanism and the growing peptide does not participates in the membrane recognition.", "contents": "[The effect of cycloheximide on incorporation of newly formed mRNA into membrane-bound polyribosomes in rat liver cells]. Incorporation kinetics of new synthesized mRNA into free and endoplasmic membrane-bound polyribosomes in the absence of normal translation (when protein synthesis in inhibited by 98% with cycloheximide) is studied. mRNA is found to incorporate into both free and bound polyribosomes. Relative content of new synthesized membrane-bound polyribosomes in the presence of cycloheximide within 2.5-4.5 hours is by 30-40% lower as compared with the control. This fact can be explained either by the absence of a growing peptide of a sufficient length, which is necessary for the formation of a part of membrane-bound polyribosomes, or by a restricted number of attachment sites on membranes as a result of delayed translation of mRNA in pre-existed polyribosomes. It is suggested that 1) the growing peptide in liver cells is responsible for the recognition of a membrane only under the formation of only one type of membrane-bound polyribosomes, or 2) the formation of all bound polyribosomes has a single mechanism and the growing peptide does not participates in the membrane recognition."} {"id": "PMID:1276272", "title": "[Changes in rabbit skeletal muscle histone concentration at different periods following denervation].", "content": "Dynamics of changes in histone fractions isolated from nuclei of rabbit skeletal muscles after the denervation is investigated by means of ion-exchange chromatography on CM-cellulose and polyacrylamide gel electrophoresis. It is shown that the content of arginine-rich histone fraction F2a1 is significantly increased, and that of lysine-rich histone fraction F1 is decreased on the sixth day after the denervation. Pre-operational injections of actinomycin D prevented these changes. The early suggestion about nervous control of transcription in rabbit skeletal muscles is confirmed.", "contents": "[Changes in rabbit skeletal muscle histone concentration at different periods following denervation]. Dynamics of changes in histone fractions isolated from nuclei of rabbit skeletal muscles after the denervation is investigated by means of ion-exchange chromatography on CM-cellulose and polyacrylamide gel electrophoresis. It is shown that the content of arginine-rich histone fraction F2a1 is significantly increased, and that of lysine-rich histone fraction F1 is decreased on the sixth day after the denervation. Pre-operational injections of actinomycin D prevented these changes. The early suggestion about nervous control of transcription in rabbit skeletal muscles is confirmed."} {"id": "PMID:1276273", "title": "[Autodegradation of rat liver polyribosomes in vitro].", "content": "In vihro decay of rat liver polyribosomes is studied under conditions of occuring phosphorolytic activity of polynucleotidephosphorylase (PNPase) and, in contrast, excluding PNPase activity (in the absence of orthophosphate). The rate of polyribosome degradation is found to be higher in the presence of orthophosphate, than in its absence. Sedimentation coefficient of ribosomes formed from degraded polyribosomes in the absence of orthophosphate is 70S, while that of ribosomes formed under phosphorolysis is 67S. It is suggested that polyribosome degradation in the presence of orthophosphate is carried out by the combined action of 5'-RNase and PNPase. 5'-RNase degrades mRNA and rRNA without disturbing the integrity of ribosomal complexes, while PNPase phosphorolyzes the fragments formed from the 3'-OH terminal, successively releasing ribosomes. The rate of polysome inactivation in the presence of orthophosphate (half-life period being approximately 17 min) is considerably higher than that in the absence of orthophosphate (half-life period being 37 min). The amount of active polysomes in samples incubated for 3 hours both in the presence and in the absence of orthophosphate is 16% and 24% of the total amount of active polysomes, respectively. It is suggested that there are a certain type of polyribosomes, which comprise about 8% of polyribosomes that can be inactivated only by PNPase.", "contents": "[Autodegradation of rat liver polyribosomes in vitro]. In vihro decay of rat liver polyribosomes is studied under conditions of occuring phosphorolytic activity of polynucleotidephosphorylase (PNPase) and, in contrast, excluding PNPase activity (in the absence of orthophosphate). The rate of polyribosome degradation is found to be higher in the presence of orthophosphate, than in its absence. Sedimentation coefficient of ribosomes formed from degraded polyribosomes in the absence of orthophosphate is 70S, while that of ribosomes formed under phosphorolysis is 67S. It is suggested that polyribosome degradation in the presence of orthophosphate is carried out by the combined action of 5'-RNase and PNPase. 5'-RNase degrades mRNA and rRNA without disturbing the integrity of ribosomal complexes, while PNPase phosphorolyzes the fragments formed from the 3'-OH terminal, successively releasing ribosomes. The rate of polysome inactivation in the presence of orthophosphate (half-life period being approximately 17 min) is considerably higher than that in the absence of orthophosphate (half-life period being 37 min). The amount of active polysomes in samples incubated for 3 hours both in the presence and in the absence of orthophosphate is 16% and 24% of the total amount of active polysomes, respectively. It is suggested that there are a certain type of polyribosomes, which comprise about 8% of polyribosomes that can be inactivated only by PNPase."} {"id": "PMID:1276274", "title": "[A kinetic study of the reactive capabilities of xanthine oxidase sulfhydryl groups with regard to n-chlormercuribenzoate].", "content": "Kinetic characteristics for reactivity of SH-groups of milk xanthine oxidase were obtained under different conditions. Two types of SH-groups with rate constant values, differing by a factor of about 50, were found in a phosphate buffer at pH 7.0. The slow stage of reaction is followed by protein precipitation. The number of fast- (12) and slowly-reacting (60) groups were calculated from the kinetic data. The blocking of the fast-reacting groups occurs without loss of the enzyme activity. The values of activation energy for the fast- and slowly-reacting groups are 15 and 48 kcal/mol respectively. The formation of the enzyme-substrate complex stabilizes the enzyme molecule; the number of fast-reacting SH-groups and the rate constant values for both types of groups remain unchanged, whereas the number of slowly-reacting SH-groups markedly decreases (37). The values of activation energy for both types of SH-groups show no changes in the presence of substrate. Conformations of the enzyme in different denaturating solvents were characterized by a number of SH-groups, reacting with p-chloromercurybenzoate. 54 groups are exposed in solutions of groups exposed in 7.0-8.5 M urea solutions is 35-38. In all solvents studied the protein molecule is probably not completely unfolded, since the number of exposed SH-groups is less than the full number of SH-groups determined by the amino acid analysis. Only 42 SH-groups reacted with 5,5'-dithiobis-(2-nitrobenzoic acid) under the same conditions.", "contents": "[A kinetic study of the reactive capabilities of xanthine oxidase sulfhydryl groups with regard to n-chlormercuribenzoate]. Kinetic characteristics for reactivity of SH-groups of milk xanthine oxidase were obtained under different conditions. Two types of SH-groups with rate constant values, differing by a factor of about 50, were found in a phosphate buffer at pH 7.0. The slow stage of reaction is followed by protein precipitation. The number of fast- (12) and slowly-reacting (60) groups were calculated from the kinetic data. The blocking of the fast-reacting groups occurs without loss of the enzyme activity. The values of activation energy for the fast- and slowly-reacting groups are 15 and 48 kcal/mol respectively. The formation of the enzyme-substrate complex stabilizes the enzyme molecule; the number of fast-reacting SH-groups and the rate constant values for both types of groups remain unchanged, whereas the number of slowly-reacting SH-groups markedly decreases (37). The values of activation energy for both types of SH-groups show no changes in the presence of substrate. Conformations of the enzyme in different denaturating solvents were characterized by a number of SH-groups, reacting with p-chloromercurybenzoate. 54 groups are exposed in solutions of groups exposed in 7.0-8.5 M urea solutions is 35-38. In all solvents studied the protein molecule is probably not completely unfolded, since the number of exposed SH-groups is less than the full number of SH-groups determined by the amino acid analysis. Only 42 SH-groups reacted with 5,5'-dithiobis-(2-nitrobenzoic acid) under the same conditions."} {"id": "PMID:1276275", "title": "[Determination of pyrimidine nucleotide sequences of DNA].", "content": "A modification of the Burton method for determination of pyrimidine nucleotide blocks (isopliths) of DNA, providing a higher yield of large-sized nucleotide isopliths, is described. The amount of side products (interisopliths) does not exceed their amount upon DNA hydrolysis according to the Burton method. Another advantage of the technique recommended is a considerable shortening of hudrolysis time (20 min instead of 18 hours). The modification described has been successfully used to determine the pyrimidine nucleotide blocks of some warm-blooded animals DNAs. It has been found that the DNA of animals with higher sensitivity to ionised irradiation contains more oligothymidylic sequences as compared to the DNA of animals, less sensitive to irradiation.", "contents": "[Determination of pyrimidine nucleotide sequences of DNA]. A modification of the Burton method for determination of pyrimidine nucleotide blocks (isopliths) of DNA, providing a higher yield of large-sized nucleotide isopliths, is described. The amount of side products (interisopliths) does not exceed their amount upon DNA hydrolysis according to the Burton method. Another advantage of the technique recommended is a considerable shortening of hudrolysis time (20 min instead of 18 hours). The modification described has been successfully used to determine the pyrimidine nucleotide blocks of some warm-blooded animals DNAs. It has been found that the DNA of animals with higher sensitivity to ionised irradiation contains more oligothymidylic sequences as compared to the DNA of animals, less sensitive to irradiation."} {"id": "PMID:1276276", "title": "[The effect of several 2-alkyl- and 4'-O-methylanalogs of pyridoxol on mouse liver pyridoxal kinase activity].", "content": "A simple method of isolation of partially purified puridoxal kinase preparation from mouse liver, having specific activity of 600-700 E/mg protein and a 30% yield is described. It is demonstrated that of all number of 2-alkyl- and 4'-O-methyl pyridoxol analogs synthesized, 4'-O-methyl-pyridoxol (Ki=0.2-10(-5) M, Km(pyridoxal)=4-10(-5) M) is the most active competitive inhibitor of pyridoxal kinase. 3-Deoxy-4'-O-methylpyridoxol is a non-competitive inhibitor of pyridoxal kinase, the latter having an affinity for the enzyme 16 times lower than that of 4'-O-methylpyridoxol. 2-Alkyl analogs of pyridoxol exhibit properties of competitive inhibitors; the affinity of 2'-ethylpyridoxol for the enzyme is 5 times lower than that of 2'-methylpyridoxol; corresponding 2-alkyl derivatives of dimethyl ethers of 3-hydroxycinchomeronic acids have no pronounced affinity for the enzyme. The study of the toxic effects of pyridoxol analogs on the central nervous system has revealed inverse dependence between the neurotoxic dose of the compound and its efficiency as an inhibitor of pyridoxal kinase (Km/Ki value).", "contents": "[The effect of several 2-alkyl- and 4'-O-methylanalogs of pyridoxol on mouse liver pyridoxal kinase activity]. A simple method of isolation of partially purified puridoxal kinase preparation from mouse liver, having specific activity of 600-700 E/mg protein and a 30% yield is described. It is demonstrated that of all number of 2-alkyl- and 4'-O-methyl pyridoxol analogs synthesized, 4'-O-methyl-pyridoxol (Ki=0.2-10(-5) M, Km(pyridoxal)=4-10(-5) M) is the most active competitive inhibitor of pyridoxal kinase. 3-Deoxy-4'-O-methylpyridoxol is a non-competitive inhibitor of pyridoxal kinase, the latter having an affinity for the enzyme 16 times lower than that of 4'-O-methylpyridoxol. 2-Alkyl analogs of pyridoxol exhibit properties of competitive inhibitors; the affinity of 2'-ethylpyridoxol for the enzyme is 5 times lower than that of 2'-methylpyridoxol; corresponding 2-alkyl derivatives of dimethyl ethers of 3-hydroxycinchomeronic acids have no pronounced affinity for the enzyme. The study of the toxic effects of pyridoxol analogs on the central nervous system has revealed inverse dependence between the neurotoxic dose of the compound and its efficiency as an inhibitor of pyridoxal kinase (Km/Ki value)."} {"id": "PMID:1276277", "title": "[Kinetics of reversible inhibition of cholinesterases by quaternary diaminoalkyl esters of aromatic dicarboxylic acids].", "content": "Reversible inhibition of acetylcholinesterase (AChE) from bovine erythrocytes and butyrylcholinesterase (BuChE) from horse blood serum by quaternary diaminoalkyl esters of suberic (D-6), p-phenylenediacetic (PK-139), p-phenylenedipropionic (PK-154 and PK-155), p-phenylenediacrylic (PK-150 and PK-151) and phthalic (PK-105) acids, was studied under the following incubation conditions: pH 7.5, 25 degrees C, 0.1 M KCl. The inhibition kinetics were of a mixed competitive-incompetitive type, the incompetitive component alpha'-having higher values for AChE (0.26-0.60) than for BuChE (0.10-0.20). Diester PK-150 selectively inhibited BuChE (Ki=3.0-10(-6) M); its Ki value for AChE was 4.0-10(-4) M. The other diesters had a stronger inhibitory effect on AChE than on BuChE. High values of alpha' observed during AChE inhibition cannot be interpreted in terms of interaction of those bisquaternary compounds with the anionic site of the acetylated active centre and are probably due to their sorbtion at the peripheral anionic sites. Incompetitive inhibition constants (K'i=Ki/alpha') of BuChE by the diesters PK-139, PK-154 and PK-150 were found to be values of the same order as substrate inhibition constants determined in the course of BuChE hydrolysis of these diesters. Incompetitive inhibition found for the esters studied and substrate inhibition during hydrolysis of these compounds are presumably due to the same mechanism.", "contents": "[Kinetics of reversible inhibition of cholinesterases by quaternary diaminoalkyl esters of aromatic dicarboxylic acids]. Reversible inhibition of acetylcholinesterase (AChE) from bovine erythrocytes and butyrylcholinesterase (BuChE) from horse blood serum by quaternary diaminoalkyl esters of suberic (D-6), p-phenylenediacetic (PK-139), p-phenylenedipropionic (PK-154 and PK-155), p-phenylenediacrylic (PK-150 and PK-151) and phthalic (PK-105) acids, was studied under the following incubation conditions: pH 7.5, 25 degrees C, 0.1 M KCl. The inhibition kinetics were of a mixed competitive-incompetitive type, the incompetitive component alpha'-having higher values for AChE (0.26-0.60) than for BuChE (0.10-0.20). Diester PK-150 selectively inhibited BuChE (Ki=3.0-10(-6) M); its Ki value for AChE was 4.0-10(-4) M. The other diesters had a stronger inhibitory effect on AChE than on BuChE. High values of alpha' observed during AChE inhibition cannot be interpreted in terms of interaction of those bisquaternary compounds with the anionic site of the acetylated active centre and are probably due to their sorbtion at the peripheral anionic sites. Incompetitive inhibition constants (K'i=Ki/alpha') of BuChE by the diesters PK-139, PK-154 and PK-150 were found to be values of the same order as substrate inhibition constants determined in the course of BuChE hydrolysis of these diesters. Incompetitive inhibition found for the esters studied and substrate inhibition during hydrolysis of these compounds are presumably due to the same mechanism."} {"id": "PMID:1276278", "title": "[Several properties of cotton seed phospholipase D].", "content": "Properties of phospholipase D were studied using purified enzyme preparation from cotton seeds. The results obtained differ from those described in literature. It has been shown that the promoting action is exerted not only by diethyl ether and sodium dodecyl sulfate commonly used as initiators, but by some organic solvents in the presence of calcium ions as well. The activation of phospholipase D is also possible in the presence of other bivalent cations, e.g. Sr2+, Ba2+, Mn2+ and Mg2+. It is assumed that the enzyme activation occurs only in the presence of the stable heterogenous system: water-soluble enzyme--phospholipid--non-aqueous phase. Another important factor is the type of modification of the surface of the phospholipid phase, responsible for the enzyme adsorption and its subsequent activation. Comparison is made of the properties of phospholipases D isolated from cotton seeds and some other sources.", "contents": "[Several properties of cotton seed phospholipase D]. Properties of phospholipase D were studied using purified enzyme preparation from cotton seeds. The results obtained differ from those described in literature. It has been shown that the promoting action is exerted not only by diethyl ether and sodium dodecyl sulfate commonly used as initiators, but by some organic solvents in the presence of calcium ions as well. The activation of phospholipase D is also possible in the presence of other bivalent cations, e.g. Sr2+, Ba2+, Mn2+ and Mg2+. It is assumed that the enzyme activation occurs only in the presence of the stable heterogenous system: water-soluble enzyme--phospholipid--non-aqueous phase. Another important factor is the type of modification of the surface of the phospholipid phase, responsible for the enzyme adsorption and its subsequent activation. Comparison is made of the properties of phospholipases D isolated from cotton seeds and some other sources."} {"id": "PMID:1276279", "title": "[Intranuclear distribution of rat liver ribosomal RNA].", "content": "A method is described for the isolation of pure liver nuclei with minimal cytoplasmic contaminants, loss of nuclear RNA and degradation of nuclear RNA. The RNA components are extracted in three distinct fractions by subsequent treatment with phenol at 4 degrees, 50 degrees and 85 degrees C. The total and 14C-orotate labelled RNA components in the three nuclear RNA fractions are characterized by nucleotide composition, poly(A)-RNA content and agar-gel electrophoresis. The results show that the RNA in three fractions correspond to the nucleosol, nucleolus and chromatin compartments of the nucleus. The nuclear HnRNA components are exclusively in the 85 degrees C RNA. Nuclear ribosomal RNA is extracted in the 4 degrees C and 50 degrees C RNA fractions. These two nuclear RNA fractions are distinct in constituent pre-rRNA species and the rate of labelling of their rRNA components. The amount of the pre-rRNA and rRNA species is determined. The results show that the nucleolus-nucleosol and nucleosol-cytoplasm transitions of ribosomal subparticles are markedly slower processes than the preceeding steps of ribosome biogenesis.", "contents": "[Intranuclear distribution of rat liver ribosomal RNA]. A method is described for the isolation of pure liver nuclei with minimal cytoplasmic contaminants, loss of nuclear RNA and degradation of nuclear RNA. The RNA components are extracted in three distinct fractions by subsequent treatment with phenol at 4 degrees, 50 degrees and 85 degrees C. The total and 14C-orotate labelled RNA components in the three nuclear RNA fractions are characterized by nucleotide composition, poly(A)-RNA content and agar-gel electrophoresis. The results show that the RNA in three fractions correspond to the nucleosol, nucleolus and chromatin compartments of the nucleus. The nuclear HnRNA components are exclusively in the 85 degrees C RNA. Nuclear ribosomal RNA is extracted in the 4 degrees C and 50 degrees C RNA fractions. These two nuclear RNA fractions are distinct in constituent pre-rRNA species and the rate of labelling of their rRNA components. The amount of the pre-rRNA and rRNA species is determined. The results show that the nucleolus-nucleosol and nucleosol-cytoplasm transitions of ribosomal subparticles are markedly slower processes than the preceeding steps of ribosome biogenesis."} {"id": "PMID:1276280", "title": "[A proteolytic enzyme bound to the aspartate transaminase of swine heart cytosol].", "content": "Purified preparations of aspartate transaminase from pig heart cytosol contain a tightly bound proteolytic enzyme (approximately 2, 5%). The enzyme was separated from aspartate transaminase by gel-filtration on Sephadex G-100 in the presence of sodium dodecyl sulfate and by affinity chromatography on the column with Sepharose, containing covalently bound denaturated aspartate transaminase. Protease has a pH optimum of 9.0 and molecular weight of about 23.000-25.000. The proteolysis rates of different subforms of aspartate transaminase depend on their denaturation lability. A more stable choloenzyme is split at a slower rate than the apoenzyme. An enriched preparation of protease was also shown to split glutamate decarboxylase from E. coli and had no effect on cysteinlyase from hen egg, as well as on lactate dehydrogenase and albumin.", "contents": "[A proteolytic enzyme bound to the aspartate transaminase of swine heart cytosol]. Purified preparations of aspartate transaminase from pig heart cytosol contain a tightly bound proteolytic enzyme (approximately 2, 5%). The enzyme was separated from aspartate transaminase by gel-filtration on Sephadex G-100 in the presence of sodium dodecyl sulfate and by affinity chromatography on the column with Sepharose, containing covalently bound denaturated aspartate transaminase. Protease has a pH optimum of 9.0 and molecular weight of about 23.000-25.000. The proteolysis rates of different subforms of aspartate transaminase depend on their denaturation lability. A more stable choloenzyme is split at a slower rate than the apoenzyme. An enriched preparation of protease was also shown to split glutamate decarboxylase from E. coli and had no effect on cysteinlyase from hen egg, as well as on lactate dehydrogenase and albumin."} {"id": "PMID:1276281", "title": "[Substrate specificity of Aspergillus clavatus intracellular acid RNAase].", "content": "Substrate specificity of intracellular acid RNAse from Aspergillus clavatus, has been studied using different RNAs, synthetic polynucleotides and diribonucleoside monophosphates as substrates. The enzyme was shown to be a RNAse, non-specific to the chemical nature of bases adjacent to the disrupted phosphodiesther bonds in the molecules of RNA. It has been demonstrated that the order of nucleotide release from RNA coincides with the order of weakening of the enzyme binding to substrates XpY, depending on the base X. Purine bases increase substrates XpY binding with the enzyme and hamper their splitting. The effect of pyrimidine bases on adsorption and catalytic functions of the enzyme is contrary to that of purine bases cited above.", "contents": "[Substrate specificity of Aspergillus clavatus intracellular acid RNAase]. Substrate specificity of intracellular acid RNAse from Aspergillus clavatus, has been studied using different RNAs, synthetic polynucleotides and diribonucleoside monophosphates as substrates. The enzyme was shown to be a RNAse, non-specific to the chemical nature of bases adjacent to the disrupted phosphodiesther bonds in the molecules of RNA. It has been demonstrated that the order of nucleotide release from RNA coincides with the order of weakening of the enzyme binding to substrates XpY, depending on the base X. Purine bases increase substrates XpY binding with the enzyme and hamper their splitting. The effect of pyrimidine bases on adsorption and catalytic functions of the enzyme is contrary to that of purine bases cited above."} {"id": "PMID:1276282", "title": "[Interaction of steroid hormones with glutamate dehydrogenase].", "content": "The inhibitory action of sex hormones on the glutamate dehydrogenase activity is due to their binding to the enzyme protein. No binding of sex hormones to glutamate dehydrogenase is observed in the presence of L-amino acids, preventing the enzyme dissociation. Under those conditions the enzyme sensitivity to the inhibitory action of the hormones sharply decreases.", "contents": "[Interaction of steroid hormones with glutamate dehydrogenase]. The inhibitory action of sex hormones on the glutamate dehydrogenase activity is due to their binding to the enzyme protein. No binding of sex hormones to glutamate dehydrogenase is observed in the presence of L-amino acids, preventing the enzyme dissociation. Under those conditions the enzyme sensitivity to the inhibitory action of the hormones sharply decreases."} {"id": "PMID:1276283", "title": "[Two forms of pea leaf ferredoxin].", "content": "Some causative factors resulting in the appearance of two components of ferredoxin (Fd) isolated from the pea leaves preparations have been studied by 15% PAG electrophoresis. It has been shown that the composition of the buffer systems (tris-glycine buffer, pH 8,3; veronal buffer, pH 7.0) does not cause Fd separation into two components. Study of the effects of the modifying agents on the active centre and apoprotein of Fd. Showed that the destruction of the active centre does not affect Fd separation and modification of the Fd protein part results in greater amount of the bands on the electrophoregrams. It has been concluded that heterogeneity of Fd is possibly of the genetic nature. The following facts can be regarded as an evidence for existence of both forms of Fd in pea leaves: occurrence of two forms of Fd in chloroplasts isolated in organic media, differing in Fd content during pea ontogenesis and upon varying illumination conditions during their growth.", "contents": "[Two forms of pea leaf ferredoxin]. Some causative factors resulting in the appearance of two components of ferredoxin (Fd) isolated from the pea leaves preparations have been studied by 15% PAG electrophoresis. It has been shown that the composition of the buffer systems (tris-glycine buffer, pH 8,3; veronal buffer, pH 7.0) does not cause Fd separation into two components. Study of the effects of the modifying agents on the active centre and apoprotein of Fd. Showed that the destruction of the active centre does not affect Fd separation and modification of the Fd protein part results in greater amount of the bands on the electrophoregrams. It has been concluded that heterogeneity of Fd is possibly of the genetic nature. The following facts can be regarded as an evidence for existence of both forms of Fd in pea leaves: occurrence of two forms of Fd in chloroplasts isolated in organic media, differing in Fd content during pea ontogenesis and upon varying illumination conditions during their growth."} {"id": "PMID:1276284", "title": "[A spectrophotometric study of Penicillium brevicompactum RNAase complex formation with adenine nucleotides].", "content": "Spectrophotometric study of extracellular Pen. brevicompactum RNAse interaction with adenyl nucleotides and constituents have been carried out. It is states that: 1) complex RNAse--nucleotide is formed by association of one enzyme molecule with one nucleotide molecule; 2) all the nucleotide components base sugar and phosphate, take part in the formation of this complex; 3) for the effective association of this complex it is necessary to have a high correspondence (complementaryty) of nucleotide geometric configuration to the space composition of the active site of RNAse.", "contents": "[A spectrophotometric study of Penicillium brevicompactum RNAase complex formation with adenine nucleotides]. Spectrophotometric study of extracellular Pen. brevicompactum RNAse interaction with adenyl nucleotides and constituents have been carried out. It is states that: 1) complex RNAse--nucleotide is formed by association of one enzyme molecule with one nucleotide molecule; 2) all the nucleotide components base sugar and phosphate, take part in the formation of this complex; 3) for the effective association of this complex it is necessary to have a high correspondence (complementaryty) of nucleotide geometric configuration to the space composition of the active site of RNAse."} {"id": "PMID:1276285", "title": "[Comparative characteristics of the \"ultrasonic\" fractions of rabbit leukocyte (neutrophil) and brain chromatin].", "content": "Ratios and composition of \"ultrasonic\" fractions of chromatin in cells with different transcription intensity were studied. The hardly extracted residual fraction of chromatin makes up to about 80% DNA in leukocytes (neutrophils) and about 20% in brain tissue. Comparative characterization of fractions showed that residual DNP of brain and liver include, in addition to fragments of inactive condensed chromatin, the sites actively involved in the synthesis of RNA. The residual DNP of leukocytes, on the contrary, possesses a number of characteristics of inactive chromatin. A hypothesis is discussed of the necessity of close contacts between the most intensively transcribed RNAs and nuclear membrane lipid components, resulting in the incorporation of transcribed sites into the residual fraction.", "contents": "[Comparative characteristics of the \"ultrasonic\" fractions of rabbit leukocyte (neutrophil) and brain chromatin]. Ratios and composition of \"ultrasonic\" fractions of chromatin in cells with different transcription intensity were studied. The hardly extracted residual fraction of chromatin makes up to about 80% DNA in leukocytes (neutrophils) and about 20% in brain tissue. Comparative characterization of fractions showed that residual DNP of brain and liver include, in addition to fragments of inactive condensed chromatin, the sites actively involved in the synthesis of RNA. The residual DNP of leukocytes, on the contrary, possesses a number of characteristics of inactive chromatin. A hypothesis is discussed of the necessity of close contacts between the most intensively transcribed RNAs and nuclear membrane lipid components, resulting in the incorporation of transcribed sites into the residual fraction."} {"id": "PMID:1276286", "title": "[Positional distribution of fatty acids in the phospholipids of regenerating rat liver].", "content": "The fatty acid composition and positioning in the glycerophospholipids from regenerating rat liver were investigated at different stages of the regeneration process. In the lecithins and phosphatidylethanolamines of the regenerating liver the content of arachidonic acid is lower and that of linoleic acid is higher than in the corresponding lipid fractions of normal rat liver. These deviations are maximal at 24 hours after hepatectomy i.e. at the onset of the mitosis. At any stage of the regeneration the high specifity of the fatty acid positioning characteristical for the normal liver is retained completely. The fatty acid composition of cardiolipin is not changed during the regeneration process.", "contents": "[Positional distribution of fatty acids in the phospholipids of regenerating rat liver]. The fatty acid composition and positioning in the glycerophospholipids from regenerating rat liver were investigated at different stages of the regeneration process. In the lecithins and phosphatidylethanolamines of the regenerating liver the content of arachidonic acid is lower and that of linoleic acid is higher than in the corresponding lipid fractions of normal rat liver. These deviations are maximal at 24 hours after hepatectomy i.e. at the onset of the mitosis. At any stage of the regeneration the high specifity of the fatty acid positioning characteristical for the normal liver is retained completely. The fatty acid composition of cardiolipin is not changed during the regeneration process."} {"id": "PMID:1276287", "title": "[The anticoagulant property of a lipoid anticoagulant and the mechanism of its influence on hemocoagulation].", "content": "A lipoid anticoagulant (LA) from human brain tissue was shown to possess a higher anticoagulant activity than previously obtained preparations. It has been established that out of four phospholipids present in LA, only phosphatidyl serine inhibits the coagulant activity of plasma. In isolated hemocoagulating systems LA and phosphatidyl serine were shown to inhibit prothrombin conversion catalyzed by thrombokinase and to exert the antithrombic action in the system thrombin--fibrinogen. Kinetic study of phosphatidyl serine- and LA-induced inhibition of thrombine formation and the thrombine--fibrinogen reaction by conjugated inhibition. Similar kinetic behaviour, observed upon inhibition of both processes by phosphatidyl serine and LA suggest that phosphatidyl serine is a main anticoagulant agent of LA.", "contents": "[The anticoagulant property of a lipoid anticoagulant and the mechanism of its influence on hemocoagulation]. A lipoid anticoagulant (LA) from human brain tissue was shown to possess a higher anticoagulant activity than previously obtained preparations. It has been established that out of four phospholipids present in LA, only phosphatidyl serine inhibits the coagulant activity of plasma. In isolated hemocoagulating systems LA and phosphatidyl serine were shown to inhibit prothrombin conversion catalyzed by thrombokinase and to exert the antithrombic action in the system thrombin--fibrinogen. Kinetic study of phosphatidyl serine- and LA-induced inhibition of thrombine formation and the thrombine--fibrinogen reaction by conjugated inhibition. Similar kinetic behaviour, observed upon inhibition of both processes by phosphatidyl serine and LA suggest that phosphatidyl serine is a main anticoagulant agent of LA."} {"id": "PMID:1276288", "title": "[The photoelectrochemical effect in solid films of flucoxanthine].", "content": "A negative photopotential was shown to appear upon illumination on a fucoxanthin solid film-covered platinum electrode, immersed into an electrolyte solution. The effects of electrolyte pH and the reducing and oxidyzing agents on the photopotential value and its kinetic behaviour upon illumination and in the dark were studied. The data obtained are indicative of the ability of fucoxanthin to perform photochemical reactions at the level of electron transfers, which accounts for its photosensitizing activity.", "contents": "[The photoelectrochemical effect in solid films of flucoxanthine]. A negative photopotential was shown to appear upon illumination on a fucoxanthin solid film-covered platinum electrode, immersed into an electrolyte solution. The effects of electrolyte pH and the reducing and oxidyzing agents on the photopotential value and its kinetic behaviour upon illumination and in the dark were studied. The data obtained are indicative of the ability of fucoxanthin to perform photochemical reactions at the level of electron transfers, which accounts for its photosensitizing activity."} {"id": "PMID:1276295", "title": "Amniotic fluid surface tension during pregnancy.", "content": "A good correlation between the amniotic fluid surface tension and gestational age was found in 51 amniotic fluid samples from normal pregnancies. The samples were obtained between the 20th and 43rd week of gestation. A good relation also exists between amniotic fluid lecithin concentration and fluid surface tension, and between said surface tension and the foam test carried out according to Clements et al. (4).", "contents": "Amniotic fluid surface tension during pregnancy. A good correlation between the amniotic fluid surface tension and gestational age was found in 51 amniotic fluid samples from normal pregnancies. The samples were obtained between the 20th and 43rd week of gestation. A good relation also exists between amniotic fluid lecithin concentration and fluid surface tension, and between said surface tension and the foam test carried out according to Clements et al. (4)."} {"id": "PMID:1276296", "title": "A micropuncture study of the development of renal function in the young rat.", "content": "Total kidney function and function of individual surface nephrons were measured under hypotonic saline load conditions in young rats 22-, 30- and 42-days old. The highest values of urine flow rate and GFR were found in 30-day-old rats. The water reabsorption was higher in 42-day-old rats than in two younger groups. This decreased fractional reabsorption of water in younger animals was detectable already in the late proximal tubule and in the early distal tubule. Fractional reabsorption of sodium was significantly lower at the age of 22 and 30 days than at the age of 42 days in both late proximal tubule and in the early distal one.", "contents": "A micropuncture study of the development of renal function in the young rat. Total kidney function and function of individual surface nephrons were measured under hypotonic saline load conditions in young rats 22-, 30- and 42-days old. The highest values of urine flow rate and GFR were found in 30-day-old rats. The water reabsorption was higher in 42-day-old rats than in two younger groups. This decreased fractional reabsorption of water in younger animals was detectable already in the late proximal tubule and in the early distal tubule. Fractional reabsorption of sodium was significantly lower at the age of 22 and 30 days than at the age of 42 days in both late proximal tubule and in the early distal one."} {"id": "PMID:1276297", "title": "Changes in the organs of pigs in response to feeding for the first 24 h after birth. III. Fluorescence histochemistry of the carbohydrates of the intestine.", "content": "The duodenum, jejunum, ileum and large intestine of newborn, and 24-hour-old fed and unfed piglets, and of 10-day-old piglets have been studied by new histochemical methods. At birth Meissner's plexus was most developed in the duodenum. There was little change during the first 24 h, but by 10 days it had become elaborated. Goblet cells were present at birth in all parts of the intestine. After 24 h a large proportion of those in the duodenum had discharged and were being replaced with a new generation. Similar changes took place more slowly in the jejunum and ileum and very much more slowly in the large intestine. Feeding increased the rate of turnover.", "contents": "Changes in the organs of pigs in response to feeding for the first 24 h after birth. III. Fluorescence histochemistry of the carbohydrates of the intestine. The duodenum, jejunum, ileum and large intestine of newborn, and 24-hour-old fed and unfed piglets, and of 10-day-old piglets have been studied by new histochemical methods. At birth Meissner's plexus was most developed in the duodenum. There was little change during the first 24 h, but by 10 days it had become elaborated. Goblet cells were present at birth in all parts of the intestine. After 24 h a large proportion of those in the duodenum had discharged and were being replaced with a new generation. Similar changes took place more slowly in the jejunum and ileum and very much more slowly in the large intestine. Feeding increased the rate of turnover."} {"id": "PMID:1276298", "title": "Amino acid pools in the feto-maternal system.", "content": "The determinations of the amino acid pools, including tryptophan (by fluorescence spectrometry), in the arterial and venous blood of the mother, the arterial and venous blood of the fetus (cord blood), the amniotic fluid and the placenta was done in eight women at the moment of delivery. Only nine amino acids (asp, try, met, phe, ser, cys, lys, gly, thr) were significantly retained and four (arg, glu, pro and glu-NH2) were significantly released by the fetal tissues. In contrast with this behavior most amino acids were retained by the maternal tissue, try, phe and hist showing the highest retention. When the amino acids are grouped as essential and nonessentials, the maternal tissues retained both categories without apparent discrimination, while the fetal tissues retained essential amino acids preferentially. Our results emphasize the importance of the placenta as the regulating system of the fetal milieu under normal conditions. Thus human fetal blood levels of amino acids are patterned after the placental ones and not after the maternal values obtained at the same time. It is apparent that the placenta seems to function as a nonspecific retention filter for outgoing amino acids, but that its function is selective in respect to the release of amino acids into the fetal circulation.", "contents": "Amino acid pools in the feto-maternal system. The determinations of the amino acid pools, including tryptophan (by fluorescence spectrometry), in the arterial and venous blood of the mother, the arterial and venous blood of the fetus (cord blood), the amniotic fluid and the placenta was done in eight women at the moment of delivery. Only nine amino acids (asp, try, met, phe, ser, cys, lys, gly, thr) were significantly retained and four (arg, glu, pro and glu-NH2) were significantly released by the fetal tissues. In contrast with this behavior most amino acids were retained by the maternal tissue, try, phe and hist showing the highest retention. When the amino acids are grouped as essential and nonessentials, the maternal tissues retained both categories without apparent discrimination, while the fetal tissues retained essential amino acids preferentially. Our results emphasize the importance of the placenta as the regulating system of the fetal milieu under normal conditions. Thus human fetal blood levels of amino acids are patterned after the placental ones and not after the maternal values obtained at the same time. It is apparent that the placenta seems to function as a nonspecific retention filter for outgoing amino acids, but that its function is selective in respect to the release of amino acids into the fetal circulation."} {"id": "PMID:1276299", "title": "Influence of early weaning on the activity of several enzymes in the liver of rat.", "content": "In normally weaned rats the activity of two enzymes in rat liver, i.e. ATP citrate lyase and malic enzyme, gradually increases between the end of the third and the beginning of the fourth postnatal week. The activity of mitochondrial alpha-glycerophosphate oxidase remains unchanged during this period. Early weaning on the 18th postnatal day causes a rapid increase in activity of these enzymes. The impulse for this increase is very probably the change from high fat milk diet to high carbohydrate standard laboratory diet, the decrease of blood lipids, the activation of thyroid gland and changes of sensitivity of hepatic cells towards thyroid hormones. These results showed that early weaning modifies to the known picture of physiological weaning to a great extent.", "contents": "Influence of early weaning on the activity of several enzymes in the liver of rat. In normally weaned rats the activity of two enzymes in rat liver, i.e. ATP citrate lyase and malic enzyme, gradually increases between the end of the third and the beginning of the fourth postnatal week. The activity of mitochondrial alpha-glycerophosphate oxidase remains unchanged during this period. Early weaning on the 18th postnatal day causes a rapid increase in activity of these enzymes. The impulse for this increase is very probably the change from high fat milk diet to high carbohydrate standard laboratory diet, the decrease of blood lipids, the activation of thyroid gland and changes of sensitivity of hepatic cells towards thyroid hormones. These results showed that early weaning modifies to the known picture of physiological weaning to a great extent."} {"id": "PMID:1276300", "title": "The effect of litter size on the growth, survival and behaviour of neonatal bulbectomised mice.", "content": "Bilateral lesions of the olfactory bulbs in 1-day-old mice led to a slow rate of growth both before and after weaning and the growth changes were positively associated with the size of the lesion. Mothers continued to care for the bulbectomised mice which showed no evidence of retarded motor development though their eyes opened later and they were less active when exposed to an artificial perfume. Bulbectomised mice failed to survive in litters of two where both infants were bulbectomised and in litters with a large number of unoperated littermates. Keeping litters small and having both bulbectomised and control mice present enhanced the chances of survival and the presence of infant control mice is a necessary condition for the maintenance of lactation and the survival of the bulbectomised babies. Failure to respond to the odours( pheromones) of the mothers may be responsible for the infrequent suckling and the slow growth and development.", "contents": "The effect of litter size on the growth, survival and behaviour of neonatal bulbectomised mice. Bilateral lesions of the olfactory bulbs in 1-day-old mice led to a slow rate of growth both before and after weaning and the growth changes were positively associated with the size of the lesion. Mothers continued to care for the bulbectomised mice which showed no evidence of retarded motor development though their eyes opened later and they were less active when exposed to an artificial perfume. Bulbectomised mice failed to survive in litters of two where both infants were bulbectomised and in litters with a large number of unoperated littermates. Keeping litters small and having both bulbectomised and control mice present enhanced the chances of survival and the presence of infant control mice is a necessary condition for the maintenance of lactation and the survival of the bulbectomised babies. Failure to respond to the odours( pheromones) of the mothers may be responsible for the infrequent suckling and the slow growth and development."} {"id": "PMID:1276301", "title": "Triglyceride mobilization in cultured adipocytes of human infants.", "content": "Cultured adipocytes of human infants, in the absence of known lipolytic agents, are capable of mobilizing their own stored triglycerides as showed by a decrease in the content of stored triglycerides with time. The medium used is synthetic, fortified with 20% fetal calf serum and contains adequate amount of glucose. It is suggested that lipolysis occurs because the metabolic balance favors lipolysis in the absence of adequate amount of free fatty acids in the medium. Conversely lipogenesis is favored in the presence of such fatty acids.", "contents": "Triglyceride mobilization in cultured adipocytes of human infants. Cultured adipocytes of human infants, in the absence of known lipolytic agents, are capable of mobilizing their own stored triglycerides as showed by a decrease in the content of stored triglycerides with time. The medium used is synthetic, fortified with 20% fetal calf serum and contains adequate amount of glucose. It is suggested that lipolysis occurs because the metabolic balance favors lipolysis in the absence of adequate amount of free fatty acids in the medium. Conversely lipogenesis is favored in the presence of such fatty acids."} {"id": "PMID:1276302", "title": "Post-natal development of factor II (pre-prothrombin and prothrombin) in man.", "content": "Postnatal development of factor II molecule has been evaluated by three different methods in infants and children from 15 days to 7 years of age. The immunochemical determination of factor II showed that the plasma levels of this factor reached the lowest adult values between 4-7 months of age and rose slowly for all the first year; after this age the plasma concentration was steady. The adult range was reached from 15 to 120 days of age when the factor II was evaluated by the method of Owren and Aas (19) and by staphylocoagulase reagent.", "contents": "Post-natal development of factor II (pre-prothrombin and prothrombin) in man. Postnatal development of factor II molecule has been evaluated by three different methods in infants and children from 15 days to 7 years of age. The immunochemical determination of factor II showed that the plasma levels of this factor reached the lowest adult values between 4-7 months of age and rose slowly for all the first year; after this age the plasma concentration was steady. The adult range was reached from 15 to 120 days of age when the factor II was evaluated by the method of Owren and Aas (19) and by staphylocoagulase reagent."} {"id": "PMID:1276303", "title": "Sex differences in patterns of EEG asymmetry.", "content": "This paper reports three studies showing sex differences in EEG asymmetry during self-generated cognitive and affective tasks. In the first experiment, bilateral EEG, quantified for alpha on-line, was recorded from right-handed subjects while they either whistled, sang or recited lyrics of familiar songs. The results revealed significant asymmetry between the whistle and talk conditions only for subjects with no familial left-handedness and, within this group, only for females and not for males. In the second experiment, bilateral EEG was recorded while right-handed subjects (with no familial left-handedness) self-induced covert affective and non-affective states. Results revealed significantly greater relative right-hemisphere activation during emotion versus non-emotion trials only in females; males showed no significant task-dependent shifts in asymmetry between conditions. The third experiment was designed to test the hypothesis that females show greater percent time asymmetry than males during biofeedback training for symmetrical and asymmetrical EEG patterns. Results confirmed this prediction as well as indicating that females show better control of such asymmetrical cortical patterning. These findings provide new neuropsychological support for the hypothesis of greater bilateral flexibility in females during self-generation tasks.", "contents": "Sex differences in patterns of EEG asymmetry. This paper reports three studies showing sex differences in EEG asymmetry during self-generated cognitive and affective tasks. In the first experiment, bilateral EEG, quantified for alpha on-line, was recorded from right-handed subjects while they either whistled, sang or recited lyrics of familiar songs. The results revealed significant asymmetry between the whistle and talk conditions only for subjects with no familial left-handedness and, within this group, only for females and not for males. In the second experiment, bilateral EEG was recorded while right-handed subjects (with no familial left-handedness) self-induced covert affective and non-affective states. Results revealed significantly greater relative right-hemisphere activation during emotion versus non-emotion trials only in females; males showed no significant task-dependent shifts in asymmetry between conditions. The third experiment was designed to test the hypothesis that females show greater percent time asymmetry than males during biofeedback training for symmetrical and asymmetrical EEG patterns. Results confirmed this prediction as well as indicating that females show better control of such asymmetrical cortical patterning. These findings provide new neuropsychological support for the hypothesis of greater bilateral flexibility in females during self-generation tasks."} {"id": "PMID:1276304", "title": "Effects of warning-signal modality on the contingent negative variation (CNV).", "content": "CNVs were recorded during the S1-S2 interval of a prolonged simple reaction task. In the task, a warning stimulus S1 is followed by an imperative stimulus S2, to which the subject makes a motor response. The differential effects of a visual and an auditory S1 were investigated under two interstimulus interval (ISI) durations (1 and 3 sec). Under the 3 sec ISI condition, the form of the slow negative wave demonstrated clearly a biphasic character: an orientation wave (O wave) following S1 with a peak latency at about 650 msec and an expectancy wave (E wave), which reaches its largest amplitude towards the end of the ISI. Under the 1 sec ISI condition the two components of the CNV are confounded. The O wave had a fronto-central distribution, while the E wave was located precentrally. The O wave was enhanced after an auditory S1, as compared to a visual S1.", "contents": "Effects of warning-signal modality on the contingent negative variation (CNV). CNVs were recorded during the S1-S2 interval of a prolonged simple reaction task. In the task, a warning stimulus S1 is followed by an imperative stimulus S2, to which the subject makes a motor response. The differential effects of a visual and an auditory S1 were investigated under two interstimulus interval (ISI) durations (1 and 3 sec). Under the 3 sec ISI condition, the form of the slow negative wave demonstrated clearly a biphasic character: an orientation wave (O wave) following S1 with a peak latency at about 650 msec and an expectancy wave (E wave), which reaches its largest amplitude towards the end of the ISI. Under the 1 sec ISI condition the two components of the CNV are confounded. The O wave had a fronto-central distribution, while the E wave was located precentrally. The O wave was enhanced after an auditory S1, as compared to a visual S1."} {"id": "PMID:1276305", "title": "The effects of controlled muscle tension on performance and learning of heart-rate control.", "content": "Thirty female subjects were divided in three groups and instructed in group I to increase their HRs with the aid of continuous feedback of performance, while they tensed their right forearm muscles 20% of maximal voluntary contraction. In the last session only feedback was used, Group II were trained with feedback only. Group III for the first two sessions tensed their muscles only, and in the last session trained HR increases with feedback only. Group I was superior in HR performance in the first two sessions. In the third session they deteriorated significantly and could not be distinguished from the other two groups. The results were interpreted in terms of relations between somatic and autonomic events and transfer between different states of somatic involvement during learning. Electrodermal activity and respiration were included as control variables.", "contents": "The effects of controlled muscle tension on performance and learning of heart-rate control. Thirty female subjects were divided in three groups and instructed in group I to increase their HRs with the aid of continuous feedback of performance, while they tensed their right forearm muscles 20% of maximal voluntary contraction. In the last session only feedback was used, Group II were trained with feedback only. Group III for the first two sessions tensed their muscles only, and in the last session trained HR increases with feedback only. Group I was superior in HR performance in the first two sessions. In the third session they deteriorated significantly and could not be distinguished from the other two groups. The results were interpreted in terms of relations between somatic and autonomic events and transfer between different states of somatic involvement during learning. Electrodermal activity and respiration were included as control variables."} {"id": "PMID:1276306", "title": "Heart-rate decelerative Pavlovian conditioning with tilt as UCS: towards behavioural control of cardiac dysfunction.", "content": "As part of a programme the ultimate goal of which is to teach behavioural control of stress-induced maladaptive cardiac accelerations through Pavlovian decelerative conditioning, this study was directed at examining the feasibility of using tilting of the body from a head-up to a head-down position as the unconditional stimulus (UCS) to elicit phasic cardiac deceleration as the unconditional response (UCR). Experiment I assessed the reflexive features of the cardiac response to 32 tilt UCS trials delivered at mean intervals of 75 sec. The results yielded a large-magnitude (over 30 BsPM) cardiac decelerative UCR with fast recruitment and complete resistance to habituation. Experiment II examined the feasibility of using the tilt UCS to demonstrate associative control over decelerative responding to a tone as the conditional stimulus (CS). Relative to a control 'backward' UCS-CS group with an interstimulus interval (ISI) of 14.5 sec, a 0.5 sec ISI CS-UCS experimental group demonstrated both orderly acquisition and extinction performance. The magnitude of the conditional deceleration of some 4 BsPM is greater than the extent of control generally achieved with biofeedback, but still constitutes a problem for theoretical accounts of classical conditioning framed in terms of stimulus substitution, and is still only of borderline clinical significance.", "contents": "Heart-rate decelerative Pavlovian conditioning with tilt as UCS: towards behavioural control of cardiac dysfunction. As part of a programme the ultimate goal of which is to teach behavioural control of stress-induced maladaptive cardiac accelerations through Pavlovian decelerative conditioning, this study was directed at examining the feasibility of using tilting of the body from a head-up to a head-down position as the unconditional stimulus (UCS) to elicit phasic cardiac deceleration as the unconditional response (UCR). Experiment I assessed the reflexive features of the cardiac response to 32 tilt UCS trials delivered at mean intervals of 75 sec. The results yielded a large-magnitude (over 30 BsPM) cardiac decelerative UCR with fast recruitment and complete resistance to habituation. Experiment II examined the feasibility of using the tilt UCS to demonstrate associative control over decelerative responding to a tone as the conditional stimulus (CS). Relative to a control 'backward' UCS-CS group with an interstimulus interval (ISI) of 14.5 sec, a 0.5 sec ISI CS-UCS experimental group demonstrated both orderly acquisition and extinction performance. The magnitude of the conditional deceleration of some 4 BsPM is greater than the extent of control generally achieved with biofeedback, but still constitutes a problem for theoretical accounts of classical conditioning framed in terms of stimulus substitution, and is still only of borderline clinical significance."} {"id": "PMID:1276331", "title": "Shear-induced hemolysis: effects of blood chemistry (including aging in storage) and shearing surfaces.", "content": "Rotating disks were used to hemolyze blood under low-stress laminar flow conditions. In the first sequence of tests, kinetic hemolysis curves (KHC) were obtained with polyethylene disks for three well-characterized bloods and repeated over a period of four weeks. Each blood had a KHC with different shape, which maintained its characteristics while aging. Correlations were sought between D6000 (percent of complete hemolysis, after 6000 sec of shear) and D0 (measured before shear) by two means of data analysis, in terms of blood chemistry. It was found that uric acid and very-low-density lipoprotein levels were most useful in predicting the characteristic D6000 vs. D0 relation for each blood, and that glucose levels correlated the rate of aging as measured by hemolysis. Other chemical factors are also displayed in terms of their influence on D0. The second series of tests consisted of comparing the KHC for four disk materials using a fourth blood, then repeating with a fifth blood. Hemolytic rankings of the materials were the same with these two blood, although the KHC shapes differed. The rankings were: polyvinyl chloride greater than Silastic approximately equal to polyethylene greater than polyether urethane, with PVC most hemolytic. In another sequence for examining materials effects, five different bloods were used to compare the hemolytic properties of Teflon, nylon, and polyethylene disks. Although the KHC for the three disks bore different relationships to each other with each different blood, extrapolation of data beyond 6000 sec suggests a ranking of Teflon greater than nylon greater than polyethylene.", "contents": "Shear-induced hemolysis: effects of blood chemistry (including aging in storage) and shearing surfaces. Rotating disks were used to hemolyze blood under low-stress laminar flow conditions. In the first sequence of tests, kinetic hemolysis curves (KHC) were obtained with polyethylene disks for three well-characterized bloods and repeated over a period of four weeks. Each blood had a KHC with different shape, which maintained its characteristics while aging. Correlations were sought between D6000 (percent of complete hemolysis, after 6000 sec of shear) and D0 (measured before shear) by two means of data analysis, in terms of blood chemistry. It was found that uric acid and very-low-density lipoprotein levels were most useful in predicting the characteristic D6000 vs. D0 relation for each blood, and that glucose levels correlated the rate of aging as measured by hemolysis. Other chemical factors are also displayed in terms of their influence on D0. The second series of tests consisted of comparing the KHC for four disk materials using a fourth blood, then repeating with a fifth blood. Hemolytic rankings of the materials were the same with these two blood, although the KHC shapes differed. The rankings were: polyvinyl chloride greater than Silastic approximately equal to polyethylene greater than polyether urethane, with PVC most hemolytic. In another sequence for examining materials effects, five different bloods were used to compare the hemolytic properties of Teflon, nylon, and polyethylene disks. Although the KHC for the three disks bore different relationships to each other with each different blood, extrapolation of data beyond 6000 sec suggests a ranking of Teflon greater than nylon greater than polyethylene."} {"id": "PMID:1276332", "title": "Intra-uterine devices, A SEM study on the Dalkon Shield.", "content": "A SEM study carried on intra-uterine devices (Dalkon Shield) is reported. The poor manufacturing of the devices is stressed, which could increase their efficiency but also the risks of penetration, or worse, perforation. The solution for the future could be copper bearing intra-uterine devices coated by hydrogels. This should maintain efficiency and improve security.", "contents": "Intra-uterine devices, A SEM study on the Dalkon Shield. A SEM study carried on intra-uterine devices (Dalkon Shield) is reported. The poor manufacturing of the devices is stressed, which could increase their efficiency but also the risks of penetration, or worse, perforation. The solution for the future could be copper bearing intra-uterine devices coated by hydrogels. This should maintain efficiency and improve security."} {"id": "PMID:1276333", "title": "Home care: a biomedical engineering challenge.", "content": "The contributions of biomedical engineering to health care delivery have focused on techniques for acquiring and processing patient data, primarily in the high technology setting of modern hospitals. The increased sophistication of hospitals is responsible in large measure for the soaring costs of health care. The current trend toward both ambulatory and home care provides new and challenging opportunities for biomedical engineering to bear on problems of great social and economic consequence in facilitating safe and effective care of the chronically ill in the security and comfort of their own homes. Techniques which are refined for use by the expanding population of both aged and handicapped individuals are also of potential value for the home care of younger patients with broader life expectancy. Projections into the future prospects for home care elicit a wide diversity of opportunities of great significance to the future of the health professions and society as a whole.", "contents": "Home care: a biomedical engineering challenge. The contributions of biomedical engineering to health care delivery have focused on techniques for acquiring and processing patient data, primarily in the high technology setting of modern hospitals. The increased sophistication of hospitals is responsible in large measure for the soaring costs of health care. The current trend toward both ambulatory and home care provides new and challenging opportunities for biomedical engineering to bear on problems of great social and economic consequence in facilitating safe and effective care of the chronically ill in the security and comfort of their own homes. Techniques which are refined for use by the expanding population of both aged and handicapped individuals are also of potential value for the home care of younger patients with broader life expectancy. Projections into the future prospects for home care elicit a wide diversity of opportunities of great significance to the future of the health professions and society as a whole."} {"id": "PMID:1276334", "title": "Ultrasonic assessment of early callus formation.", "content": "A 0.5 MHz pulse-transmission ultrasonic device is described and results obtained with an animal model presented. Two waveform components have been identified which correlate with the healing process. The \"bone wave\" is indicative of endosteal callus formation and the strength of cortical union. The \"callus wave\" is indicative of early periosteal callus formation. Recordings are presented to demonstrate the nature of the in vivo recordings, and the changes seen during the early stages of healing. In vitro recordings are presented to demonstrate that the signals are indicative of the properties of the bone and fracture, and are not soft tissue artifacts.", "contents": "Ultrasonic assessment of early callus formation. A 0.5 MHz pulse-transmission ultrasonic device is described and results obtained with an animal model presented. Two waveform components have been identified which correlate with the healing process. The \"bone wave\" is indicative of endosteal callus formation and the strength of cortical union. The \"callus wave\" is indicative of early periosteal callus formation. Recordings are presented to demonstrate the nature of the in vivo recordings, and the changes seen during the early stages of healing. In vitro recordings are presented to demonstrate that the signals are indicative of the properties of the bone and fracture, and are not soft tissue artifacts."} {"id": "PMID:1276335", "title": "A system for rapid analysis of long-term recordings of heart rate and other physiological parameters.", "content": "Using miniature cassette tape recorders, measurement of ECG and other physiological measures is possible in industrial or working situations. The development of a semi-automatic high speed processing system for analysis of the tape recorded data is described. This system decodes the signals on the tape, converts ECG to heart rate and presents a listing of the heart rate variation over the recording period, which may be up to 24 hours. A punched paper tape copy of the listing is used for input into a mainframe computer for subsequent analysis. The recorders and processing system have been used extensively for three years on a study of industrial work stress, and have proved reliable, accurate, and of sufficient sensitivity for in-depth analysis. They allow considerable data to be collected, permitting the thorough statistical analysis necessary for the interpretation of complex physiological responses.", "contents": "A system for rapid analysis of long-term recordings of heart rate and other physiological parameters. Using miniature cassette tape recorders, measurement of ECG and other physiological measures is possible in industrial or working situations. The development of a semi-automatic high speed processing system for analysis of the tape recorded data is described. This system decodes the signals on the tape, converts ECG to heart rate and presents a listing of the heart rate variation over the recording period, which may be up to 24 hours. A punched paper tape copy of the listing is used for input into a mainframe computer for subsequent analysis. The recorders and processing system have been used extensively for three years on a study of industrial work stress, and have proved reliable, accurate, and of sufficient sensitivity for in-depth analysis. They allow considerable data to be collected, permitting the thorough statistical analysis necessary for the interpretation of complex physiological responses."} {"id": "PMID:1276336", "title": "Microprocessors in health care: panacea or more effervescent technology?", "content": "The impact of microprocessors on medical instrumentation is explored, with particular reference to their role within a health care system that has finite resources. The authors present two examples of microprocessor use from their own experience and attempt to highlight both the merits and the disadvantages of the use of such technology by the hospital medical engineer.", "contents": "Microprocessors in health care: panacea or more effervescent technology? The impact of microprocessors on medical instrumentation is explored, with particular reference to their role within a health care system that has finite resources. The authors present two examples of microprocessor use from their own experience and attempt to highlight both the merits and the disadvantages of the use of such technology by the hospital medical engineer."} {"id": "PMID:1276337", "title": "A bioengineering analysis of force actions at the knee in normal and pathological gait.", "content": "The paper describes a simplified bioengineering analysis for the determination of force actions at the knee joint for normal and pathological gaits. The stance phase of the gait cycle only is considered, and gravitational and inertia forces are excluded from the analysis. The anatomical and functional assumptions required for analysis are discussed. Force actions transmitted at the knee joint by the bearing surfaces, muscles and ligaments for normal individuals are presented with reference to magnitude and phasic relationship for the activity of level walking. Bearing loads transmitted at the knee joints of pathological limbs are also discussed.", "contents": "A bioengineering analysis of force actions at the knee in normal and pathological gait. The paper describes a simplified bioengineering analysis for the determination of force actions at the knee joint for normal and pathological gaits. The stance phase of the gait cycle only is considered, and gravitational and inertia forces are excluded from the analysis. The anatomical and functional assumptions required for analysis are discussed. Force actions transmitted at the knee joint by the bearing surfaces, muscles and ligaments for normal individuals are presented with reference to magnitude and phasic relationship for the activity of level walking. Bearing loads transmitted at the knee joints of pathological limbs are also discussed."} {"id": "PMID:1276338", "title": "Development of a valve for internal drainage of ascites into the venous system.", "content": "A valve for transfer of ascites into the inferior vena caval system, has been developed. The valve answers the specific problems of this pathological condition, namely chemical composition and quantity of fluid and pressure gradient. The valve has been used in preliminary experiments carried out on dogs. The results obtained were encouraging.", "contents": "Development of a valve for internal drainage of ascites into the venous system. A valve for transfer of ascites into the inferior vena caval system, has been developed. The valve answers the specific problems of this pathological condition, namely chemical composition and quantity of fluid and pressure gradient. The valve has been used in preliminary experiments carried out on dogs. The results obtained were encouraging."} {"id": "PMID:1276339", "title": "A calibration system for catheter transducer pressure measurement.", "content": "A patient-isolated calibration system is described for use with catheter transducer physiological pressure measuring apparatus. A subatmospheric calibration pressure is applied to the rear of the transducer diaphragm, the latter isolating the patient hydraulic circuit from the calibration system. The calibration system need not therefore be sterile and remains assembled to the transducer table. Risk of air embolus in the patient and of over-pressurising the transducer during calibration are minimised. Simplification of the hydraulic circuit reduces the chance of air entrapment, improving frequency response and reproducability of results and preparation time is greatly reduced. The system is easy to make and has proved simple, rugged and reliable in use.", "contents": "A calibration system for catheter transducer pressure measurement. A patient-isolated calibration system is described for use with catheter transducer physiological pressure measuring apparatus. A subatmospheric calibration pressure is applied to the rear of the transducer diaphragm, the latter isolating the patient hydraulic circuit from the calibration system. The calibration system need not therefore be sterile and remains assembled to the transducer table. Risk of air embolus in the patient and of over-pressurising the transducer during calibration are minimised. Simplification of the hydraulic circuit reduces the chance of air entrapment, improving frequency response and reproducability of results and preparation time is greatly reduced. The system is easy to make and has proved simple, rugged and reliable in use."} {"id": "PMID:1276365", "title": "Data analysis problems in the area of pharmacokinetics research.", "content": "Of interest in compartment analysis is the estimation of kinetic first order rate constants and quantification of the amount of drug present in each compartment at every point in time. From the data pertaining to only one compartment, it is not always possible to estimate all the first order rate parameters of linear and non-linear compartment systems. When multiple varying doses are administered at different intervals of time, the equations quantifying the maximum and minimum amount of drug accumulated in each interval may be used. To obtain estimates of kinetic parameters, statistical adjustments may be used in the kinetic equations.", "contents": "Data analysis problems in the area of pharmacokinetics research. Of interest in compartment analysis is the estimation of kinetic first order rate constants and quantification of the amount of drug present in each compartment at every point in time. From the data pertaining to only one compartment, it is not always possible to estimate all the first order rate parameters of linear and non-linear compartment systems. When multiple varying doses are administered at different intervals of time, the equations quantifying the maximum and minimum amount of drug accumulated in each interval may be used. To obtain estimates of kinetic parameters, statistical adjustments may be used in the kinetic equations."} {"id": "PMID:1276366", "title": "Estimating mean time to reach a milestone, using retrospective data.", "content": "In surveys to estimate the mean age at menarche (or another milestone reached by the whole population), interviewed girls in the age range can respond that menarche (a) has not occurred or (b) has occurred or (c) occurred at a certain age t. Answers of type (a) and (b) are called status quo data. Answers of type (a) and (c) are called retrospective data.One kind of data is assumed. The distribution of age at menarche may also be assumed to be normal or not necessarily normal. This gives four possible sets of assumptions. Estimators, with their asymptotic distributions and optimal sampling allocations, are found for the case of retrospective data and non-normal distribution. These estimators are compared in examples with previously proposed estimators based on the other sets of assumptions. In these examples, retrospective data should certainly be used if available and reliable.", "contents": "Estimating mean time to reach a milestone, using retrospective data. In surveys to estimate the mean age at menarche (or another milestone reached by the whole population), interviewed girls in the age range can respond that menarche (a) has not occurred or (b) has occurred or (c) occurred at a certain age t. Answers of type (a) and (b) are called status quo data. Answers of type (a) and (c) are called retrospective data.One kind of data is assumed. The distribution of age at menarche may also be assumed to be normal or not necessarily normal. This gives four possible sets of assumptions. Estimators, with their asymptotic distributions and optimal sampling allocations, are found for the case of retrospective data and non-normal distribution. These estimators are compared in examples with previously proposed estimators based on the other sets of assumptions. In these examples, retrospective data should certainly be used if available and reliable."} {"id": "PMID:1276367", "title": "An exact test of the Hardy-Weinberg law.", "content": "An exact distribution of a finite sample drawn from an infinite population in Hardy-Weinberg Equilibrium is described for k-alleles. Accordingly, an exact test of the law is presented and compared with two x2-tests for two and three alleles. For two alleles, it is shown that the \"classical\" c2-test is very adequate for sample sizes as small as ten. For three alleles, it is shown that a simpler formulation based on Leven's distribution approximates the exact test of this paper rather closely. However, it is recommended that researchers continue to employ the standard x2-test for all sample sizes and abide by it if the corresponding probability value is not \"too close\" to the critical level; otherwise, an exact test should be used.", "contents": "An exact test of the Hardy-Weinberg law. An exact distribution of a finite sample drawn from an infinite population in Hardy-Weinberg Equilibrium is described for k-alleles. Accordingly, an exact test of the law is presented and compared with two x2-tests for two and three alleles. For two alleles, it is shown that the \"classical\" c2-test is very adequate for sample sizes as small as ten. For three alleles, it is shown that a simpler formulation based on Leven's distribution approximates the exact test of this paper rather closely. However, it is recommended that researchers continue to employ the standard x2-test for all sample sizes and abide by it if the corresponding probability value is not \"too close\" to the critical level; otherwise, an exact test should be used."} {"id": "PMID:1276369", "title": "Parameter estimation in studying circadian rhythms.", "content": "In the model under consideration for the circadian rhythm study there are three unknown physiological parameters involved: the level, the amplitude and the phase. This paper concerns the estimation of the group level, group amplitude and group phase of a certain group of individuals based on their time series data. Special attention is paid to the amplitude and phase parameters, and solutions are obtained for both the small-sample and the large-sample cases.", "contents": "Parameter estimation in studying circadian rhythms. In the model under consideration for the circadian rhythm study there are three unknown physiological parameters involved: the level, the amplitude and the phase. This paper concerns the estimation of the group level, group amplitude and group phase of a certain group of individuals based on their time series data. Special attention is paid to the amplitude and phase parameters, and solutions are obtained for both the small-sample and the large-sample cases."} {"id": "PMID:1276370", "title": "[The influence of glucagon on post-heparin plasma lipolytic activity in normal rats and in rats with diabetes induced by alloxan injection].", "content": "The authors compared the effect of glucagon on the post-heparinic lipolytic activity in normal and alloxan induced diabetic rats. Within their experimental conditions, it was considered that an injury of the cell stimulates a decrease of the glucagon-stimulating activity on the lipoprotein lipase: this hormone does not seem to have a direct action on the PHLA but an indirect one by the way of the insulin secretion it induces.", "contents": "[The influence of glucagon on post-heparin plasma lipolytic activity in normal rats and in rats with diabetes induced by alloxan injection]. The authors compared the effect of glucagon on the post-heparinic lipolytic activity in normal and alloxan induced diabetic rats. Within their experimental conditions, it was considered that an injury of the cell stimulates a decrease of the glucagon-stimulating activity on the lipoprotein lipase: this hormone does not seem to have a direct action on the PHLA but an indirect one by the way of the insulin secretion it induces."} {"id": "PMID:1276371", "title": "[Perfecting of a technic for the in vivo study of intestinal absorption of monosaccharides in rats].", "content": "A method for in vivo perfusion of isolated jejunal and ileal loops with catheterisation of the efferent veins is described in the rat. The haemodynamical, histological results and the steadiness of D-glucose absorption showed that there functional ability was preserved at least during one hour. D-glucose is absorbed faster by the jejunal than the ileal portion in the rat.", "contents": "[Perfecting of a technic for the in vivo study of intestinal absorption of monosaccharides in rats]. A method for in vivo perfusion of isolated jejunal and ileal loops with catheterisation of the efferent veins is described in the rat. The haemodynamical, histological results and the steadiness of D-glucose absorption showed that there functional ability was preserved at least during one hour. D-glucose is absorbed faster by the jejunal than the ileal portion in the rat."} {"id": "PMID:1276372", "title": "[The geography of leukemias and hematosarcomas].", "content": "The geography of leukemias and haematosarcomas is comprised of two parts 1) The study of geographic lymphomas, Burkitt tumor, and alpha heavy chain disease. 2) The general geography of leukemias and haematosarcomas a) leukemias: variations of frequency according to the country, variations of the frequency of different forms of leukemia, temporal variations b) haematosarcomas, increased frequency in hot countries, unequal distribution of Hodgkin's disease in children and adults. Geography of animal and human leukemias. First description of \"ethnologic hematology\".", "contents": "[The geography of leukemias and hematosarcomas]. The geography of leukemias and haematosarcomas is comprised of two parts 1) The study of geographic lymphomas, Burkitt tumor, and alpha heavy chain disease. 2) The general geography of leukemias and haematosarcomas a) leukemias: variations of frequency according to the country, variations of the frequency of different forms of leukemia, temporal variations b) haematosarcomas, increased frequency in hot countries, unequal distribution of Hodgkin's disease in children and adults. Geography of animal and human leukemias. First description of \"ethnologic hematology\"."} {"id": "PMID:1276373", "title": "A study of protoplasmic streaming in Nitella by laser Doppler spectroscopy.", "content": "Laser light scattered from particles in the streaming protoplasm of a living cell is shifted in frequency by the Doppler effect. The spectrum of the scattered light can be measured and interpreted to infer details of the velocity distribution in the protoplasm. We have developed this approach to study the protoplasmic streaming in the fresh-water alga Nitella. Our results indicate a characteristic flow pattern to which diffusion makes a negligible contribution. No difference in the velocity of particles of different size is indicated. The streaming velocity linearly with temperature with a supraoptimal temperature of 34 degrees C, and the velocity distribution becomes narrower at high temperatures. The protoplasmic streaming can be inhibited by laser light, and this effect has been used to study the photoresponse of the algae. Using beam diameters of about 50 mum, we have shown that the inhibition is very local, becoming minimal at a displacement of about 200 mum in the upstream direction and 400 mum in the downstream direction. Prolonged exposure produces a bleached area free of chloroplasts, which is three orders of magnitude less sensitive to photoinhibition.", "contents": "A study of protoplasmic streaming in Nitella by laser Doppler spectroscopy. Laser light scattered from particles in the streaming protoplasm of a living cell is shifted in frequency by the Doppler effect. The spectrum of the scattered light can be measured and interpreted to infer details of the velocity distribution in the protoplasm. We have developed this approach to study the protoplasmic streaming in the fresh-water alga Nitella. Our results indicate a characteristic flow pattern to which diffusion makes a negligible contribution. No difference in the velocity of particles of different size is indicated. The streaming velocity linearly with temperature with a supraoptimal temperature of 34 degrees C, and the velocity distribution becomes narrower at high temperatures. The protoplasmic streaming can be inhibited by laser light, and this effect has been used to study the photoresponse of the algae. Using beam diameters of about 50 mum, we have shown that the inhibition is very local, becoming minimal at a displacement of about 200 mum in the upstream direction and 400 mum in the downstream direction. Prolonged exposure produces a bleached area free of chloroplasts, which is three orders of magnitude less sensitive to photoinhibition."} {"id": "PMID:1276374", "title": "Distribution of bacteria in the velocity gradient centrifuge.", "content": "Cells in different parts of the cell cycle can be separated by brief centrifugation in a density stabilized gradient: the Mitchison-Vincent technique. The position of a cell in the tube depends upon its size, shape, and density, upon the gradients of density, viscosity, and centrifugal force through which it sediments, and upon time. A program to compute the velocities and integrate the velocity profile for particles of a particular size class is presented. Because enteric bacteria are a form intermediate between right cylinders and prolate ellipsoids of revolution, the program uses values for the frictional coefficient intermediate between those calculated for ellipsoids and for cylinders. The formula f=6pietab(a/b)1/2 possesses this property and because of its simplicity greatly speeds the calculations. A second program computes the distribution of masses and then of sedimentation constants for a bacterial population, expressed either as a frequency distribution or as total mass per s-class. The effect of the known variation in cell size at division is included in these calculations, which apply to organisms undergoing balanced, asynchronous growth in which mass increase is proportional to cell size. The two programs in conjunction compute the mass or cell-number profile in an arbitrary gradient. The programs have been used to design gradients to maximize the resolution of the technique.", "contents": "Distribution of bacteria in the velocity gradient centrifuge. Cells in different parts of the cell cycle can be separated by brief centrifugation in a density stabilized gradient: the Mitchison-Vincent technique. The position of a cell in the tube depends upon its size, shape, and density, upon the gradients of density, viscosity, and centrifugal force through which it sediments, and upon time. A program to compute the velocities and integrate the velocity profile for particles of a particular size class is presented. Because enteric bacteria are a form intermediate between right cylinders and prolate ellipsoids of revolution, the program uses values for the frictional coefficient intermediate between those calculated for ellipsoids and for cylinders. The formula f=6pietab(a/b)1/2 possesses this property and because of its simplicity greatly speeds the calculations. A second program computes the distribution of masses and then of sedimentation constants for a bacterial population, expressed either as a frequency distribution or as total mass per s-class. The effect of the known variation in cell size at division is included in these calculations, which apply to organisms undergoing balanced, asynchronous growth in which mass increase is proportional to cell size. The two programs in conjunction compute the mass or cell-number profile in an arbitrary gradient. The programs have been used to design gradients to maximize the resolution of the technique."} {"id": "PMID:1276375", "title": "A diffusion driven instability in systems that separate particles by velocity sedimentation.", "content": "Velocity sedimentation has been used extensively to separate particles according to the magnitude of their sedimentation velocity in suitable media. This technique has been used over a wide range of particle size from protein molecules, viruses, subcellular particles to whole cells. Successful separation demands that collective particle motion should not occur. In practice it is observed that such systems may, under certain circumstances, suffer from a particular type of instability which destroys the normal dependence of sedimentation velocity on particle size and density. The aim of this paper is to identify the critical parameters that determine the development of this instability. Stability criteria are deduced and predictions of the theory compared with published observations. Satisfactory agreement between theory and observation is obtained. It is concluded that the simple stability criterion, namely that stable sedimentation will occur if the total density gradient is in the direction of the sedimenting force, grossly overestimates the particle load that can be separated in practice. Some specific recommendations for optimum particle loading are included. Earlier theoretical and experimental works are briefly reviewed.", "contents": "A diffusion driven instability in systems that separate particles by velocity sedimentation. Velocity sedimentation has been used extensively to separate particles according to the magnitude of their sedimentation velocity in suitable media. This technique has been used over a wide range of particle size from protein molecules, viruses, subcellular particles to whole cells. Successful separation demands that collective particle motion should not occur. In practice it is observed that such systems may, under certain circumstances, suffer from a particular type of instability which destroys the normal dependence of sedimentation velocity on particle size and density. The aim of this paper is to identify the critical parameters that determine the development of this instability. Stability criteria are deduced and predictions of the theory compared with published observations. Satisfactory agreement between theory and observation is obtained. It is concluded that the simple stability criterion, namely that stable sedimentation will occur if the total density gradient is in the direction of the sedimenting force, grossly overestimates the particle load that can be separated in practice. Some specific recommendations for optimum particle loading are included. Earlier theoretical and experimental works are briefly reviewed."} {"id": "PMID:1276376", "title": "Absence of biomagnetic effects in Nitella.", "content": "The ability of N. flexilis and N. translucens to survive exposure to magnetic fields up to 1.6 T for extended periods of time was tested. Internodal cells subjected to such fields for as long as 72 h showed no evidence of damage. The active response of internodal cells was studied using an especially constructed sample chamber which allowed the use of intracellular microelectrodes. Action potentials in longitudinal and transverse fields as large as 2.0 T appeared identical to those in zero field. The results are in sharp contrast to observations reported by Arajs et al. (1975, Proceedings of the International Conference on Magnetism and Magnetic Materials).", "contents": "Absence of biomagnetic effects in Nitella. The ability of N. flexilis and N. translucens to survive exposure to magnetic fields up to 1.6 T for extended periods of time was tested. Internodal cells subjected to such fields for as long as 72 h showed no evidence of damage. The active response of internodal cells was studied using an especially constructed sample chamber which allowed the use of intracellular microelectrodes. Action potentials in longitudinal and transverse fields as large as 2.0 T appeared identical to those in zero field. The results are in sharp contrast to observations reported by Arajs et al. (1975, Proceedings of the International Conference on Magnetism and Magnetic Materials)."} {"id": "PMID:1276377", "title": "Temperature dependency of the rate of electron transport as a monitor of protein motion.", "content": "The temperature dependency of the rate of biological electron transport is interpreted as evolving from a contraction of the electron transport components. A theoretical expression for this temperature dependency is derived in terms of the coefficient of linear expansion (a) of the protein components. Using this expression alpha is calculated for several electron transport systems and shown to be similar to alpha-values of synthetic polymers. A discontinuity in alpha is shown to be present in all biological electron transport reactions at ca. 150 K. This discontinuity is interpreted as a change in the intramolecular bonding of the electron transport protein units.", "contents": "Temperature dependency of the rate of electron transport as a monitor of protein motion. The temperature dependency of the rate of biological electron transport is interpreted as evolving from a contraction of the electron transport components. A theoretical expression for this temperature dependency is derived in terms of the coefficient of linear expansion (a) of the protein components. Using this expression alpha is calculated for several electron transport systems and shown to be similar to alpha-values of synthetic polymers. A discontinuity in alpha is shown to be present in all biological electron transport reactions at ca. 150 K. This discontinuity is interpreted as a change in the intramolecular bonding of the electron transport protein units."} {"id": "PMID:1276378", "title": "Formation of planar bilayer membranes from lipid monolayers. A critique.", "content": "The formation of planar bilayer membranes from lipid monolayers as described by Montal and Mueller (Proc. Natl. Acad. Sci. 1972. 69:3561) is analyzed. Bilayers absolutely free of alkane solvents or other nonpolar hydrocarbons can be formed on polytetrafluoroethylene (PTFE) (e.g. Teflon) septa only if certain boundary conditions are satisfied. Measurements have been made of the contact angles between monolayer-coated water and PTFE in the presence and absence of alkane solvents. The measurement suggest that the boundary conditions for formation of stable bilayers can be satisfied only when a nonpolar solvent is present. We conclude that the bilayer must be surrounded by a torus of alkane solvent, petroleum jelly, or silicone grease depending upon the details of technique used to form the bilayer. The non-polar solvent used in the formation of the bilayer may or may not be present in the bilayer depending upon the water solubility and size of the solvent molecule relative to the size of the alkyl chain of the lipid. Detailed sketches describing the formation of bilayers from monolayers are presented.", "contents": "Formation of planar bilayer membranes from lipid monolayers. A critique. The formation of planar bilayer membranes from lipid monolayers as described by Montal and Mueller (Proc. Natl. Acad. Sci. 1972. 69:3561) is analyzed. Bilayers absolutely free of alkane solvents or other nonpolar hydrocarbons can be formed on polytetrafluoroethylene (PTFE) (e.g. Teflon) septa only if certain boundary conditions are satisfied. Measurements have been made of the contact angles between monolayer-coated water and PTFE in the presence and absence of alkane solvents. The measurement suggest that the boundary conditions for formation of stable bilayers can be satisfied only when a nonpolar solvent is present. We conclude that the bilayer must be surrounded by a torus of alkane solvent, petroleum jelly, or silicone grease depending upon the details of technique used to form the bilayer. The non-polar solvent used in the formation of the bilayer may or may not be present in the bilayer depending upon the water solubility and size of the solvent molecule relative to the size of the alkyl chain of the lipid. Detailed sketches describing the formation of bilayers from monolayers are presented."} {"id": "PMID:1276379", "title": "Phase determination of x-ray reflections for membrane-type systems with constant fluid density.", "content": "A new technique for phase determination of X-ray reflections from symmetric structures is presented. This method, involving comparison of intensity data from structures with variable fluid layer thickness and constant fluid electron density, permits computation of phase angles, scaling factors, and origin reflection values independently. Possible sources of error inherent in other methods of phase determination are thereby eliminated. Results of the application of this method to model structures and to myelin data are reported. Advantages of the technique, which tests all possible phase angle combinations in a rapid fashion, are discussed.", "contents": "Phase determination of x-ray reflections for membrane-type systems with constant fluid density. A new technique for phase determination of X-ray reflections from symmetric structures is presented. This method, involving comparison of intensity data from structures with variable fluid layer thickness and constant fluid electron density, permits computation of phase angles, scaling factors, and origin reflection values independently. Possible sources of error inherent in other methods of phase determination are thereby eliminated. Results of the application of this method to model structures and to myelin data are reported. Advantages of the technique, which tests all possible phase angle combinations in a rapid fashion, are discussed."} {"id": "PMID:1276380", "title": "Effects of ultraviolet irradiation on the rate and sequence of DNA replication in synchronized Chinese hamster cells.", "content": "The effects of ultraviolet light (UV) irradiation on the rate of DNA replication in synchronized Chinese hamster ovary (CHO) cells were investigated. A technique for measuring semiconservative DNA replication was employed that involved growing the cells in medium containing 5-bromodeoxyuridine and subsequently determining the amount of DNA that acquired hybrid buoyant density in CsCl density gradients. One of the advantages of this technique was that it allowed a characterization of the extent of DNA replication as well as rate after irradiation. It was found that while there was a dose-dependent reduction in the rate of DNA replication following UV-irradiation, doses of up to 10 J/m2 (which produce many dimers per replication) did not prevent the ultimate replication of the entire genome. Hence, we conclude that dimers cannot be absolute blocks to DNA replication. In order to account for the total genome replication observed, a mechanism must exist that allows genome replication between dimers. The degree of reduction in the rate of replication by UV was the same whether the cells were irradiated at the G1-S boundary or 1 h into S-phase. Previous work had shown that cells in early S-phase are considerably more sensitive to UV than cells at the G1-S boundary. Experiments specifically designed to test for reiterative replication showed that UV does not induce a second round of DNA replication within the same S-phase.", "contents": "Effects of ultraviolet irradiation on the rate and sequence of DNA replication in synchronized Chinese hamster cells. The effects of ultraviolet light (UV) irradiation on the rate of DNA replication in synchronized Chinese hamster ovary (CHO) cells were investigated. A technique for measuring semiconservative DNA replication was employed that involved growing the cells in medium containing 5-bromodeoxyuridine and subsequently determining the amount of DNA that acquired hybrid buoyant density in CsCl density gradients. One of the advantages of this technique was that it allowed a characterization of the extent of DNA replication as well as rate after irradiation. It was found that while there was a dose-dependent reduction in the rate of DNA replication following UV-irradiation, doses of up to 10 J/m2 (which produce many dimers per replication) did not prevent the ultimate replication of the entire genome. Hence, we conclude that dimers cannot be absolute blocks to DNA replication. In order to account for the total genome replication observed, a mechanism must exist that allows genome replication between dimers. The degree of reduction in the rate of replication by UV was the same whether the cells were irradiated at the G1-S boundary or 1 h into S-phase. Previous work had shown that cells in early S-phase are considerably more sensitive to UV than cells at the G1-S boundary. Experiments specifically designed to test for reiterative replication showed that UV does not induce a second round of DNA replication within the same S-phase."} {"id": "PMID:1276381", "title": "A possible mechanism for concentrating sodium and potassium in the cell nucleus.", "content": "A dynamic, nonequilibrium mechanism is proposed for concentrating both Na+ and K+ in the cell nucleus. The model is consistent with experiment observations and with known properties of cell membranes. This model could explaing the high nucleoplasm to cytoplasm ratios of Na+ and/or K+ reported for liver kidney, thymus, frog skin, ascites cells, and amphibian oocytes.", "contents": "A possible mechanism for concentrating sodium and potassium in the cell nucleus. A dynamic, nonequilibrium mechanism is proposed for concentrating both Na+ and K+ in the cell nucleus. The model is consistent with experiment observations and with known properties of cell membranes. This model could explaing the high nucleoplasm to cytoplasm ratios of Na+ and/or K+ reported for liver kidney, thymus, frog skin, ascites cells, and amphibian oocytes."} {"id": "PMID:1276382", "title": "Application of splines to the calculation of bacterial swimming speed distributions.", "content": "A new method of extracting information about bacterial speeds from photon correlation spectroscopy is presented. This method has the advantage that an estimation of the translational speed distribution is directly varied so as to achieve a best least-squares fit to the experimental autocorrelation function. The theory of spline approximations to continuous functions is briefly outlined. The importance of the previously disregarded diffusional component of bacterial motion is discussed. Experimental data from Salmonella at a low scattering angle is analyzed by this method of spline approximation and the distribution of translational speeds is obtained.", "contents": "Application of splines to the calculation of bacterial swimming speed distributions. A new method of extracting information about bacterial speeds from photon correlation spectroscopy is presented. This method has the advantage that an estimation of the translational speed distribution is directly varied so as to achieve a best least-squares fit to the experimental autocorrelation function. The theory of spline approximations to continuous functions is briefly outlined. The importance of the previously disregarded diffusional component of bacterial motion is discussed. Experimental data from Salmonella at a low scattering angle is analyzed by this method of spline approximation and the distribution of translational speeds is obtained."} {"id": "PMID:1276383", "title": "Picosecond kinetics of the fluorescence from the chromophore of the purple membrane protein of Halobacterium halobium.", "content": "The fluorescence emission kinetics at 740 nm of the retinylidence chromophore of the purple membrane protein of Halobacterium halobium have been studied. Using picosecond laser pulses and an optical Kerr gate, the fluorescence risetime is found to be less than 8 ps and its lifetime is 40 +/- 5 ps at 90 degrees K and is estimated to be less than 3 ps at room temperature.", "contents": "Picosecond kinetics of the fluorescence from the chromophore of the purple membrane protein of Halobacterium halobium. The fluorescence emission kinetics at 740 nm of the retinylidence chromophore of the purple membrane protein of Halobacterium halobium have been studied. Using picosecond laser pulses and an optical Kerr gate, the fluorescence risetime is found to be less than 8 ps and its lifetime is 40 +/- 5 ps at 90 degrees K and is estimated to be less than 3 ps at room temperature."} {"id": "PMID:1276384", "title": "Effect of a phase transition on the binding of 1-anilino-8-naphthalenesulfonate to phospholipid membranes.", "content": "The binding of 1-anilino-8-naphthalenesulfonate (ANS) to dipalmitoyl-phosphatidycholine (DPPC)-sonicated vesicles was measured by a fluorimetric method in the vicinity of the gel-to-liquid crystalline phase transition temperature (Tm). A similar measurement was performed on large multimellar DPPC vesicles through equilibrium dialysis. Both measurements demonstrated anomalous dye binding in the temperature region of the Tm and slightly above (prefreezing region). The amount of ANS bound at this temperature region was in excess of what would be expected based on extrapolation of the high temperature binding data; just below the Tm, the amount of bound dye decreased abruptly. The fluorimetric studies on vesicles also indicated that inner monolayer binding of ANS was markedly inhibited below the Tm. The possibility that the increase in bound dye in the prefreezing region was caused by enhanced lateral compressibility, density fluctuations, or additional binding sites at the boundary of transient gel-like clusters is discussed and the general topic of anomalous increases in various membrane processes in the vicinity of a phase transition is briefly reviewed.", "contents": "Effect of a phase transition on the binding of 1-anilino-8-naphthalenesulfonate to phospholipid membranes. The binding of 1-anilino-8-naphthalenesulfonate (ANS) to dipalmitoyl-phosphatidycholine (DPPC)-sonicated vesicles was measured by a fluorimetric method in the vicinity of the gel-to-liquid crystalline phase transition temperature (Tm). A similar measurement was performed on large multimellar DPPC vesicles through equilibrium dialysis. Both measurements demonstrated anomalous dye binding in the temperature region of the Tm and slightly above (prefreezing region). The amount of ANS bound at this temperature region was in excess of what would be expected based on extrapolation of the high temperature binding data; just below the Tm, the amount of bound dye decreased abruptly. The fluorimetric studies on vesicles also indicated that inner monolayer binding of ANS was markedly inhibited below the Tm. The possibility that the increase in bound dye in the prefreezing region was caused by enhanced lateral compressibility, density fluctuations, or additional binding sites at the boundary of transient gel-like clusters is discussed and the general topic of anomalous increases in various membrane processes in the vicinity of a phase transition is briefly reviewed."} {"id": "PMID:1276385", "title": "Heat transfer from spheres and other animal forms.", "content": "A general predictive relation for the convection heat transfer from animal forms is developed. This relation is based on the convection equation for a sphere, and employs a simple, unique characteristic dimension to represent the animal which is the cube root of the animal volume. The accuracy of this relation is established through comparison with available convection results from animal shapes ranging in size and shape from spiders to cows. This relation allows an extrapolation to animal shapes for which data are not available. Results are also presented for the enhancement of convection heat transfer due to natural turbulence. A procedure is outlined for estimating the convecture heat loss from an animal in the natural outdoor environment.", "contents": "Heat transfer from spheres and other animal forms. A general predictive relation for the convection heat transfer from animal forms is developed. This relation is based on the convection equation for a sphere, and employs a simple, unique characteristic dimension to represent the animal which is the cube root of the animal volume. The accuracy of this relation is established through comparison with available convection results from animal shapes ranging in size and shape from spiders to cows. This relation allows an extrapolation to animal shapes for which data are not available. Results are also presented for the enhancement of convection heat transfer due to natural turbulence. A procedure is outlined for estimating the convecture heat loss from an animal in the natural outdoor environment."} {"id": "PMID:1276386", "title": "Elastic area compressibility modulus of red cell membrane.", "content": "Micropipette measurements of isotropic tension vs. area expansion in pre-swollen single human red cells gave a value of 288 +/- 50 SD dyn/cm for the elastic, area compressibility modulus of the total membrane at 25 degrees C. This elastic constant, characterizing the resistance to area expansion or compression, is about 4 X 10(4) times greater than the elastic modulus for shear rigidity; therefore, in situations where deformation of the membrane does not require large isotropic tensions (e.g., in passage through normal capillaries), the membrane can be treated by a simple constitutive relation for a two-dimensionally, incompressible material (i.e. fixed area). The tension was found to be linear and reversible for the range of area changes observed (within the experimental system resolution of 10%). The maximum fractional area expansion required to produce lysis was uniformly distributed between 2 and 4% with 3% average and 0.7% SD. By heating the cells to 50 degrees C, it appears that the structural matrix (responsible for the shear rigidity and most of the strength in isotropic tension) is disrupted and primarily the lipid bilayer resists lysis. Therefore, the relative contributions of the structural matrix and lipid bilayer to the elastic, area compressibility could be estimated. The maximum isotropic tension at 25 degrees C is 10-12 dyn/cm and at 50 degrees C is between 3 and 4 dyn/cm. From this data, the respective compressibilities are estimated at 193 dyn/cm and 95 dyn/cm for structural network and bilayer. The latter value correlates well with data on in vitro, monolayer surface pressure versus area curves at oil-water interfaces.", "contents": "Elastic area compressibility modulus of red cell membrane. Micropipette measurements of isotropic tension vs. area expansion in pre-swollen single human red cells gave a value of 288 +/- 50 SD dyn/cm for the elastic, area compressibility modulus of the total membrane at 25 degrees C. This elastic constant, characterizing the resistance to area expansion or compression, is about 4 X 10(4) times greater than the elastic modulus for shear rigidity; therefore, in situations where deformation of the membrane does not require large isotropic tensions (e.g., in passage through normal capillaries), the membrane can be treated by a simple constitutive relation for a two-dimensionally, incompressible material (i.e. fixed area). The tension was found to be linear and reversible for the range of area changes observed (within the experimental system resolution of 10%). The maximum fractional area expansion required to produce lysis was uniformly distributed between 2 and 4% with 3% average and 0.7% SD. By heating the cells to 50 degrees C, it appears that the structural matrix (responsible for the shear rigidity and most of the strength in isotropic tension) is disrupted and primarily the lipid bilayer resists lysis. Therefore, the relative contributions of the structural matrix and lipid bilayer to the elastic, area compressibility could be estimated. The maximum isotropic tension at 25 degrees C is 10-12 dyn/cm and at 50 degrees C is between 3 and 4 dyn/cm. From this data, the respective compressibilities are estimated at 193 dyn/cm and 95 dyn/cm for structural network and bilayer. The latter value correlates well with data on in vitro, monolayer surface pressure versus area curves at oil-water interfaces."} {"id": "PMID:1276387", "title": "Constitutive relation for red cell membrane. Correction.", "content": "The intention of this note is to correct a subtle and somewhat esoteric error that the author discovered in his previous publications on membrane elastic behavior. The consitutive relation between membrane force resultants and large, elastic deformations of a membrane surface involves a strain tensor, characterizing the finite deformations. The original strain tensor that appeared in the equations was the Lagrangian strain tensor; however, the proper strain representation (also Lagrangian in nature because it is \"measured\" relative to the undeformed material state) is transformed by rotations of coordinates in the deformed material state (whereas the Lagrangian strain tensor is transformed by rotations of coordinates in the undeformed state). The principal membrane tensions are unchanged by this correction; the material elastic constants remain the same; and therefore, the material behavior in shear and isotropic tension is the same. However, the tensor, constitutive relation can be properly applied to coordinate systems other than the principal axis system.", "contents": "Constitutive relation for red cell membrane. Correction. The intention of this note is to correct a subtle and somewhat esoteric error that the author discovered in his previous publications on membrane elastic behavior. The consitutive relation between membrane force resultants and large, elastic deformations of a membrane surface involves a strain tensor, characterizing the finite deformations. The original strain tensor that appeared in the equations was the Lagrangian strain tensor; however, the proper strain representation (also Lagrangian in nature because it is \"measured\" relative to the undeformed material state) is transformed by rotations of coordinates in the deformed material state (whereas the Lagrangian strain tensor is transformed by rotations of coordinates in the undeformed state). The principal membrane tensions are unchanged by this correction; the material elastic constants remain the same; and therefore, the material behavior in shear and isotropic tension is the same. However, the tensor, constitutive relation can be properly applied to coordinate systems other than the principal axis system."} {"id": "PMID:1276388", "title": "Analysis of freeze-fracture electron micrographs by a computer-based technique.", "content": "A procedure is described for deriving a numerical characterization of membrane particle patterns revealed in freeze-fracture electron micrographs. Rectangular coordinates of the particles are obtained with high precision by means of an electronic digitizing device. These coordinates are fed into a large computer and analyzed in terms of (alpha) a local particle density function in terms of variable subdivisions of the membrane, and (beta) an interparticle distance function describing describing all particle pairs within the membrane. It is found that the particle density function gives the most useful description of clustering provided that particle-free patches are monitored along with nonvanishing particle densities. Theoretical particle patterns are generated with the computer by means of a random number generator to provide defined aggregation states which serve as standards of comparison for observed particle patterns.", "contents": "Analysis of freeze-fracture electron micrographs by a computer-based technique. A procedure is described for deriving a numerical characterization of membrane particle patterns revealed in freeze-fracture electron micrographs. Rectangular coordinates of the particles are obtained with high precision by means of an electronic digitizing device. These coordinates are fed into a large computer and analyzed in terms of (alpha) a local particle density function in terms of variable subdivisions of the membrane, and (beta) an interparticle distance function describing describing all particle pairs within the membrane. It is found that the particle density function gives the most useful description of clustering provided that particle-free patches are monitored along with nonvanishing particle densities. Theoretical particle patterns are generated with the computer by means of a random number generator to provide defined aggregation states which serve as standards of comparison for observed particle patterns."} {"id": "PMID:1276389", "title": "Action currents, internodal potentials, and extracellular records of myelinated mammalian nerve fibers derived from node potentials.", "content": "The potential distribution within the internodal axon of mammalian nerve fibers is derived by applying known node potential waveforms to the ends of an equivalent circuit model of the internode. The complete spatial/temporal profile of action potentials synthesized from the internodal profiles is used to compute the node current waveforn, and the extracellular action potential around fibers captured within a tubular electrode. For amphibia, the results agreed with empirical values. For mammals, the amplitude of the node currents plotted against conduction velocity was fitted by a straight line. The extracellular potential waveform depended on the location of the nodes within the tube. For tubes of length from 2 to 8 internodes, extracellular wave amplitude (mammals) was about one-third of the product of peak node current and tube resistance (center to ends). The extracellular potentials developed by longitudinal and radial currents in an anisotropic medium (fiber bundle) are compared.", "contents": "Action currents, internodal potentials, and extracellular records of myelinated mammalian nerve fibers derived from node potentials. The potential distribution within the internodal axon of mammalian nerve fibers is derived by applying known node potential waveforms to the ends of an equivalent circuit model of the internode. The complete spatial/temporal profile of action potentials synthesized from the internodal profiles is used to compute the node current waveforn, and the extracellular action potential around fibers captured within a tubular electrode. For amphibia, the results agreed with empirical values. For mammals, the amplitude of the node currents plotted against conduction velocity was fitted by a straight line. The extracellular potential waveform depended on the location of the nodes within the tube. For tubes of length from 2 to 8 internodes, extracellular wave amplitude (mammals) was about one-third of the product of peak node current and tube resistance (center to ends). The extracellular potentials developed by longitudinal and radial currents in an anisotropic medium (fiber bundle) are compared."} {"id": "PMID:1276390", "title": "Experimental measurement of the stiffness of the cupula.", "content": "An experimental procedure is described which consists of cutting the canal duct, inserting a micropipette and administering known volumetric displacements to the cupula. The cupula is made visible by dying the endolymph. Known displacements are administered to the cupula, and the time constant of the return to its equilibrium position is measured. With this information, the stiffness of the cupula is calculated. The experiment was successfully carried out on five White King pigeons. The mean stiffness found in somewhat less than other results reported in the literature, and reasons for this discrepancy are noted.", "contents": "Experimental measurement of the stiffness of the cupula. An experimental procedure is described which consists of cutting the canal duct, inserting a micropipette and administering known volumetric displacements to the cupula. The cupula is made visible by dying the endolymph. Known displacements are administered to the cupula, and the time constant of the return to its equilibrium position is measured. With this information, the stiffness of the cupula is calculated. The experiment was successfully carried out on five White King pigeons. The mean stiffness found in somewhat less than other results reported in the literature, and reasons for this discrepancy are noted."} {"id": "PMID:1276391", "title": "Liquid membrane potential in nonisothermal systems.", "content": "Electrical membrane potential equations for liquid ion exchange membranes, characterized by the presence of uncharged associated species and by exclusion of co-ions (no electrolyte uptake) have been derived. The irreversible thermodynamic theories already developed for solid membranes with fixed charged site density have been extended to include the different physicochemical aspects of the liquid membranes. To this purpose the dissipation function has been written with reference to the fluxes of all the species present in the membrane. It has been found that the mobile charged site, the counterions, and the uncharged associated species contribute to the electrical membrane potential through their phenomenological coefficients. The electrical membrane potential equations have been integrated in isothermal and nonisothermal conditions for monoionic and biionic systems. The theoretical predictions have been experimentally tested by studying the electrical potential of liquid membranes formed with solutions of tetraheptylammonium salts in omicron-dichlorobenzene.", "contents": "Liquid membrane potential in nonisothermal systems. Electrical membrane potential equations for liquid ion exchange membranes, characterized by the presence of uncharged associated species and by exclusion of co-ions (no electrolyte uptake) have been derived. The irreversible thermodynamic theories already developed for solid membranes with fixed charged site density have been extended to include the different physicochemical aspects of the liquid membranes. To this purpose the dissipation function has been written with reference to the fluxes of all the species present in the membrane. It has been found that the mobile charged site, the counterions, and the uncharged associated species contribute to the electrical membrane potential through their phenomenological coefficients. The electrical membrane potential equations have been integrated in isothermal and nonisothermal conditions for monoionic and biionic systems. The theoretical predictions have been experimentally tested by studying the electrical potential of liquid membranes formed with solutions of tetraheptylammonium salts in omicron-dichlorobenzene."} {"id": "PMID:1276392", "title": "The kinetics of cholesterol oxidase synthesis by Nocardia rhodocrous.", "content": "The production of cholesterol oxidase by 3 liter batch cultures of Nocardia rhodocrous growing on a glycerol/yeast extract medium was investigated. Cholesterol was shown to be a good inducer of the enzyme. The optimum time for cholesterol addition and the quantity to be added were determined, resulting in a 15-fold yield increase. Cholesterol oxidase synthesis was influenced by the dissolved oxygen tension. Maximum cholesterol oxidase production was obtained at 30-40% air saturation. The effect of growth conditions on the extraction of cholesterol oxidase by Triton X-100 was investigated. The scale-up of the fermentation to 800 liters in a pilot-plant fermenter is described.", "contents": "The kinetics of cholesterol oxidase synthesis by Nocardia rhodocrous. The production of cholesterol oxidase by 3 liter batch cultures of Nocardia rhodocrous growing on a glycerol/yeast extract medium was investigated. Cholesterol was shown to be a good inducer of the enzyme. The optimum time for cholesterol addition and the quantity to be added were determined, resulting in a 15-fold yield increase. Cholesterol oxidase synthesis was influenced by the dissolved oxygen tension. Maximum cholesterol oxidase production was obtained at 30-40% air saturation. The effect of growth conditions on the extraction of cholesterol oxidase by Triton X-100 was investigated. The scale-up of the fermentation to 800 liters in a pilot-plant fermenter is described."} {"id": "PMID:1276393", "title": "A model for enzymatic isomerization of D-glucose to D-fructose in a batch reactor.", "content": "Using whole cells containing glucose isomerase, mathematical models for the enzymatic conversion of D-glucose to D-fructose and for the inactivation of the enzyme catalyst have been postulated and verified experimentally. The heat of reaction, the equilibrium constant, and the individual rate constants and their activation energies have been estimated. The model can be used to predict the time course for the enzymatic production of fructose in a batch reactor within the tested experimental range of 40-80 degrees C.", "contents": "A model for enzymatic isomerization of D-glucose to D-fructose in a batch reactor. Using whole cells containing glucose isomerase, mathematical models for the enzymatic conversion of D-glucose to D-fructose and for the inactivation of the enzyme catalyst have been postulated and verified experimentally. The heat of reaction, the equilibrium constant, and the individual rate constants and their activation energies have been estimated. The model can be used to predict the time course for the enzymatic production of fructose in a batch reactor within the tested experimental range of 40-80 degrees C."} {"id": "PMID:1276394", "title": "Effects of immobilization on the kinetics of enzyme-catalyzed reactions. I. Glucose oxidase in a recirculation reactor system.", "content": "Glucose oxidase from Aspergillus niger was immobilized on nonporous glass beads by covalent bonding and its kinetics were studied in a packed-column recycle reactor. The optimum pH of the immobilized enzyme was the same as that of soluble enzyme; however, immobilized glucose oxidase showed a sharper pH-activity profile than that of the soluble enzyme. The kinetic behavior of immobilized glucose oxidase at optimum pH and 25 degrees C was similar to that of the soluble enzyme, but the immobilized material showed increased temperature sensitivity. Immobilized glucose oxidase showed no loss in activity on storage at 4 degrees C for nearly ten weeks. On continuous use for 60 hr, the immobilized enzyme showed about a 40% loss in activity but no change in the kinetic constant.", "contents": "Effects of immobilization on the kinetics of enzyme-catalyzed reactions. I. Glucose oxidase in a recirculation reactor system. Glucose oxidase from Aspergillus niger was immobilized on nonporous glass beads by covalent bonding and its kinetics were studied in a packed-column recycle reactor. The optimum pH of the immobilized enzyme was the same as that of soluble enzyme; however, immobilized glucose oxidase showed a sharper pH-activity profile than that of the soluble enzyme. The kinetic behavior of immobilized glucose oxidase at optimum pH and 25 degrees C was similar to that of the soluble enzyme, but the immobilized material showed increased temperature sensitivity. Immobilized glucose oxidase showed no loss in activity on storage at 4 degrees C for nearly ten weeks. On continuous use for 60 hr, the immobilized enzyme showed about a 40% loss in activity but no change in the kinetic constant."} {"id": "PMID:1276395", "title": "Effects of immobilization on the kinetics of enzyme-catalyzed reactions. II. Urease in a packed-column differential reactor system.", "content": "Urease from Jack bean was immobilized on nonporous glass beads by covalent bonding and its kinetics were studied in a packed-column differential reactor. To facilitate comparison, the urease was immobilized by both diazo and glutaraldehyde coupling. The kinetic properties of immobilized urease were similar to those of the soluble enzyme and different immobilization methods did not appreciably alter the kinetic properties. The affects of three different amino acid activators appear to follow predictions obtained from a relatively simple competitive model, except at very low substrate levels.", "contents": "Effects of immobilization on the kinetics of enzyme-catalyzed reactions. II. Urease in a packed-column differential reactor system. Urease from Jack bean was immobilized on nonporous glass beads by covalent bonding and its kinetics were studied in a packed-column differential reactor. To facilitate comparison, the urease was immobilized by both diazo and glutaraldehyde coupling. The kinetic properties of immobilized urease were similar to those of the soluble enzyme and different immobilization methods did not appreciably alter the kinetic properties. The affects of three different amino acid activators appear to follow predictions obtained from a relatively simple competitive model, except at very low substrate levels."} {"id": "PMID:1276398", "title": "[A histochemical study of the distribution of plasminogen activator in myocardial tissue in experimental ischemia].", "content": "The level of plasminogen activator activity studied by histochemical method in the myocardial tissue of rats during experimental ischemia was decreased if compared with control animals. The maximal decrease was seen the next day after the occlusion of the coronary artery, particularly in the necrotic zone. Plasminogen activator activity level began to increase in 3 days. Histochemical data were confirmed biochemically.", "contents": "[A histochemical study of the distribution of plasminogen activator in myocardial tissue in experimental ischemia]. The level of plasminogen activator activity studied by histochemical method in the myocardial tissue of rats during experimental ischemia was decreased if compared with control animals. The maximal decrease was seen the next day after the occlusion of the coronary artery, particularly in the necrotic zone. Plasminogen activator activity level began to increase in 3 days. Histochemical data were confirmed biochemically."} {"id": "PMID:1276399", "title": "[The influence of several surface-active substances on neuromuscular transmission of excitation].", "content": "Microelectrode method was applied to the study of the influence of sodium bile salts (BS), saponin and between-80 on the end-plate potentials (EPP) of m. sartorius of Rana ridibunda. Bile salts in a concentration of 10(-5) g/ml did not change these potentials significantly. With increase of the BS concentration up to 10(-4) g/ml the amplitude of EPP increased 1.5- 3 times. The action of these substances in a concentration up to 10(-3) g/ml caused similar, but more rapid, increase in the EPP amplitude, and then the amplitude decreased. Saponin and tween-80 were less efffective in their action on EPP, but evoked muscle contraction. It is suggested that an increase in the EPP amplitude as a result of the action of the mentioned agents was chiefly connected with stimulation of the acetylcholine release by the nerve terminals.", "contents": "[The influence of several surface-active substances on neuromuscular transmission of excitation]. Microelectrode method was applied to the study of the influence of sodium bile salts (BS), saponin and between-80 on the end-plate potentials (EPP) of m. sartorius of Rana ridibunda. Bile salts in a concentration of 10(-5) g/ml did not change these potentials significantly. With increase of the BS concentration up to 10(-4) g/ml the amplitude of EPP increased 1.5- 3 times. The action of these substances in a concentration up to 10(-3) g/ml caused similar, but more rapid, increase in the EPP amplitude, and then the amplitude decreased. Saponin and tween-80 were less efffective in their action on EPP, but evoked muscle contraction. It is suggested that an increase in the EPP amplitude as a result of the action of the mentioned agents was chiefly connected with stimulation of the acetylcholine release by the nerve terminals."} {"id": "PMID:1276400", "title": "[Elastic properties of the atria and characteristics of atrial mechanoreceptors].", "content": "Acute experiments were conducted on cats; a recording was made of the sum total activity of the mechanoreceptors of the right auricle, pressure in the auricle and its extension. It was demonstrated that extensibility of the auricles sharpely decreased with the pressure of over 5mm Hg, whereas with high pressure there was seen a marked increase in the sensitivity of the mechanoreceptors to the auricular extension. Due to this linear relationship between the pressure in the auricle and the activity of the mechanoreceptors was etained this permitting them to supply information to the rcentral nervous system concerning the auricular pressur with its change within a wide range.", "contents": "[Elastic properties of the atria and characteristics of atrial mechanoreceptors]. Acute experiments were conducted on cats; a recording was made of the sum total activity of the mechanoreceptors of the right auricle, pressure in the auricle and its extension. It was demonstrated that extensibility of the auricles sharpely decreased with the pressure of over 5mm Hg, whereas with high pressure there was seen a marked increase in the sensitivity of the mechanoreceptors to the auricular extension. Due to this linear relationship between the pressure in the auricle and the activity of the mechanoreceptors was etained this permitting them to supply information to the rcentral nervous system concerning the auricular pressur with its change within a wide range."} {"id": "PMID:1276401", "title": "[Experimental vestibulopathy produced as a result of formation of a generator of pathologically enhanced excitation in the vestibular nuclei (phenomenon of a determinative dispatch station)].", "content": "A possibility of formation of a generator of pathologically enhanced excitation in the system of the vestibular nuclei of the medulla oblongata by disturbance of their inhibitory processes (resulting in development of contralateral rotatory motions in animals) was shown. Experiments with electrical stimulation of the lateral vestibular nucleus and its coagulation showed the system of the vestibular neurons organizing the synchronous message by the vestibulo-spinal pathways to underlie the generator of the pathologically enhanced excitation. It was concluded that the generator of the pathologically enhanced excitation formed in the lateral vestibular nucleus as a result of disturbed inhibition underlied the hyperactive determinative dispatch station causing the syndrome of vestibulopathy", "contents": "[Experimental vestibulopathy produced as a result of formation of a generator of pathologically enhanced excitation in the vestibular nuclei (phenomenon of a determinative dispatch station)]. A possibility of formation of a generator of pathologically enhanced excitation in the system of the vestibular nuclei of the medulla oblongata by disturbance of their inhibitory processes (resulting in development of contralateral rotatory motions in animals) was shown. Experiments with electrical stimulation of the lateral vestibular nucleus and its coagulation showed the system of the vestibular neurons organizing the synchronous message by the vestibulo-spinal pathways to underlie the generator of the pathologically enhanced excitation. It was concluded that the generator of the pathologically enhanced excitation formed in the lateral vestibular nucleus as a result of disturbed inhibition underlied the hyperactive determinative dispatch station causing the syndrome of vestibulopathy"} {"id": "PMID:1276402", "title": "[Dynamics of the responsiveness of the mesenteric microvessels of rats with experimental renal and hormonal hypertension].", "content": "Reactivity of mesenteric arterioles (10- 30 mu in diameter) was studied in vivo after the application of histamine 100- 500 gamma), adrenaline, noradrenaline, and acetylcholine (1- 10 mug) in normal rats and in the animals with renal and hormonal hypertension. Sensitivity of microvessels to the action of vasoactive substances proved to change depending on the stage of hypertension.", "contents": "[Dynamics of the responsiveness of the mesenteric microvessels of rats with experimental renal and hormonal hypertension]. Reactivity of mesenteric arterioles (10- 30 mu in diameter) was studied in vivo after the application of histamine 100- 500 gamma), adrenaline, noradrenaline, and acetylcholine (1- 10 mug) in normal rats and in the animals with renal and hormonal hypertension. Sensitivity of microvessels to the action of vasoactive substances proved to change depending on the stage of hypertension."} {"id": "PMID:1276403", "title": "[External respiration and the functional state of the respiratory center in hypoxia developing against a background of inactivated carbonic anhydrase].", "content": "Experiments were conducted on cats; inactivation of carboanhydrase with diamox prevented developmento f hypocapnia and disturbances of the rhythmic activity of the respiratory neurons associated with it in acute hypoxia. However, comparision of electrophysiological data, external respiration indices, of the acid-base balance, pO2 and pCO2 of arterial blood demonstrated that, preventing development of pathological Cheyne-Stokes respiration under conditions of hypoxia, inactivation of carboanhydrase with diamox caused dissociation of the thoracic and abdominal respiration and dyspnea. The latter led to shifts in the metabolic processes and to disturbance of the electrolyte metabolism at the cell level.", "contents": "[External respiration and the functional state of the respiratory center in hypoxia developing against a background of inactivated carbonic anhydrase]. Experiments were conducted on cats; inactivation of carboanhydrase with diamox prevented developmento f hypocapnia and disturbances of the rhythmic activity of the respiratory neurons associated with it in acute hypoxia. However, comparision of electrophysiological data, external respiration indices, of the acid-base balance, pO2 and pCO2 of arterial blood demonstrated that, preventing development of pathological Cheyne-Stokes respiration under conditions of hypoxia, inactivation of carboanhydrase with diamox caused dissociation of the thoracic and abdominal respiration and dyspnea. The latter led to shifts in the metabolic processes and to disturbance of the electrolyte metabolism at the cell level."} {"id": "PMID:1276404", "title": "[The influence of oxygen barotherapy on erythropoiesis in the recuperative period of hemorrhagic collapse].", "content": "Under the effect of high-pressure oxygen therapy (2 atm of O2 for 40 min) in anemic rats (blood loss - 2,8% of body weight in the course of 30 min) erythropoiesis in the bone marrow was more intense and led to effective restoration of erythrocytes and hemoglobin in the peripheral blood. Biphasic character of accumulation of erythropoientins in the blood serum of rats was seen on the 1st and the 10th days after acute blood loss. Erythropoiesis inhibitor was revealed in the blood serum of rats on the 15th day. A conclusion was drawn on the importance of erythropoietins and high pressure oxygen therapy in the mechanism of blood regeneration following the loss of blood.", "contents": "[The influence of oxygen barotherapy on erythropoiesis in the recuperative period of hemorrhagic collapse]. Under the effect of high-pressure oxygen therapy (2 atm of O2 for 40 min) in anemic rats (blood loss - 2,8% of body weight in the course of 30 min) erythropoiesis in the bone marrow was more intense and led to effective restoration of erythrocytes and hemoglobin in the peripheral blood. Biphasic character of accumulation of erythropoientins in the blood serum of rats was seen on the 1st and the 10th days after acute blood loss. Erythropoiesis inhibitor was revealed in the blood serum of rats on the 15th day. A conclusion was drawn on the importance of erythropoietins and high pressure oxygen therapy in the mechanism of blood regeneration following the loss of blood."} {"id": "PMID:1276405", "title": "[The effect of intravenous novocaine administration on the outcome of hemorrhagic reactions].", "content": "Experiments conducted on 48 dogs and 50 rabbits showed that intravenous injection of novocain at various periods of the organism reaction to acute massive hemorrhage promoted an increase of survival and of the life span of the animals. Administration of the preparation increase the rate of flow, cardiac stroke and minute volume, and, on the whole, prevented the occurrence of late period of hemorrhagic shock. A conclusion was drawn that intravenous injections of novocain delayed the rate of development of the pathological process, and thus promoted more complete mobilization of the compensatory reactions.", "contents": "[The effect of intravenous novocaine administration on the outcome of hemorrhagic reactions]. Experiments conducted on 48 dogs and 50 rabbits showed that intravenous injection of novocain at various periods of the organism reaction to acute massive hemorrhage promoted an increase of survival and of the life span of the animals. Administration of the preparation increase the rate of flow, cardiac stroke and minute volume, and, on the whole, prevented the occurrence of late period of hemorrhagic shock. A conclusion was drawn that intravenous injections of novocain delayed the rate of development of the pathological process, and thus promoted more complete mobilization of the compensatory reactions."} {"id": "PMID:1276406", "title": "[Neurospecific protein S-100 in the synaptosomes of rat cerebral cortex].", "content": "Neurospecific S-100 protein was revealed by the methods of microelectrophoresis in the 15% polyacrylamide gel with a 0.1% sodium dodecylsulfate and by a highly purified S-100 protein \"marker\" in the composition of low molecular acidic proteins of the rat brain synaptosomes. The S-100 protein conten constitutes about 15-2o% of the low molecular acidic synaptosomal porteins in the rat brain.", "contents": "[Neurospecific protein S-100 in the synaptosomes of rat cerebral cortex]. Neurospecific S-100 protein was revealed by the methods of microelectrophoresis in the 15% polyacrylamide gel with a 0.1% sodium dodecylsulfate and by a highly purified S-100 protein \"marker\" in the composition of low molecular acidic proteins of the rat brain synaptosomes. The S-100 protein conten constitutes about 15-2o% of the low molecular acidic synaptosomal porteins in the rat brain."} {"id": "PMID:1276407", "title": "[Possible role of adenine nucleotide transport in regulating the respiration of rat liver mitochondria].", "content": "Studies with liver mitochondria from rats which starved for 48 hours showed the rate of ADP-stimulated respiration to be 20% lower than in the presence of an uncoupler. This effect was eliminated by preincubation of mitochondria with carnitine. Mitochondria from fed rats were characterized by a considerable decrease of states 3 and 4 respiration. In this case carnitine produced no effect. Preincubation of mitochondria from the liver of fed rats with alpha-ketoglutarate resulted in a substantial increase of the states 3 and 4 respiratory rates. There proved to exist at least two types of regulation of adenine nucleotide transport through the inner mitochondrial membrane depending on the metabolic state of the organism, i.e. by inhibition of adenine-nucleotide translocase by cytoplasmic acyl-CoAs and by control of intramitochondrial adenine nucleotide pool.", "contents": "[Possible role of adenine nucleotide transport in regulating the respiration of rat liver mitochondria]. Studies with liver mitochondria from rats which starved for 48 hours showed the rate of ADP-stimulated respiration to be 20% lower than in the presence of an uncoupler. This effect was eliminated by preincubation of mitochondria with carnitine. Mitochondria from fed rats were characterized by a considerable decrease of states 3 and 4 respiration. In this case carnitine produced no effect. Preincubation of mitochondria from the liver of fed rats with alpha-ketoglutarate resulted in a substantial increase of the states 3 and 4 respiratory rates. There proved to exist at least two types of regulation of adenine nucleotide transport through the inner mitochondrial membrane depending on the metabolic state of the organism, i.e. by inhibition of adenine-nucleotide translocase by cytoplasmic acyl-CoAs and by control of intramitochondrial adenine nucleotide pool."} {"id": "PMID:1276408", "title": "[The dynamics of serotonin in tissues in acute hypoxia (the phenomenon and its possible significance].", "content": "Serotonin (5HT) decreased in the bone marrow and renal cortex, and hyperserotoninemia developed immediately after one-hour hypoxia. Six-hour hypoxia was followed by an additional decrease of 5-HT in the kidney, medulla, spleen and thymus. Phasic changes of the 5-HT TOOK PLACE at the posthypoxic period. Apparently hypoxia led to the 5-HT mobilization and an increase of its biosynthesis. A possible significance of the 5-HT for the control of hemopoiesis both at the level of the kidney and directly al the level of hemopoietic cells is discussed.", "contents": "[The dynamics of serotonin in tissues in acute hypoxia (the phenomenon and its possible significance]. Serotonin (5HT) decreased in the bone marrow and renal cortex, and hyperserotoninemia developed immediately after one-hour hypoxia. Six-hour hypoxia was followed by an additional decrease of 5-HT in the kidney, medulla, spleen and thymus. Phasic changes of the 5-HT TOOK PLACE at the posthypoxic period. Apparently hypoxia led to the 5-HT mobilization and an increase of its biosynthesis. A possible significance of the 5-HT for the control of hemopoiesis both at the level of the kidney and directly al the level of hemopoietic cells is discussed."} {"id": "PMID:1276409", "title": "[Changes in the creatine kinase activity of the brain, heart, liver and plasma of rats subjected to oxygen starvation].", "content": "The action of hypoxic and cytotoxic hypoxia on the creatine phosphokinase activity in the blood plasma, cardiac and hepatic tissue, cerebral tissue, as well as on the nuclear and mitochondrial cerebral fractions was investigated. Oxygen deficiency was followed by significant changes of the creatine kinase activity in all the tissues and cell fractions under investigation. The type of changes depended on the isoenzyme tissue perculiarities, as well as on the state of the enzyme oxidative phosphorylation systems and membrane permeability.", "contents": "[Changes in the creatine kinase activity of the brain, heart, liver and plasma of rats subjected to oxygen starvation]. The action of hypoxic and cytotoxic hypoxia on the creatine phosphokinase activity in the blood plasma, cardiac and hepatic tissue, cerebral tissue, as well as on the nuclear and mitochondrial cerebral fractions was investigated. Oxygen deficiency was followed by significant changes of the creatine kinase activity in all the tissues and cell fractions under investigation. The type of changes depended on the isoenzyme tissue perculiarities, as well as on the state of the enzyme oxidative phosphorylation systems and membrane permeability."} {"id": "PMID:1276410", "title": "[The concentration and bisynthesis of ubiquinone-9 in the liver of white rats adapted to altitude hypoxia].", "content": "The content and biosynthesis of ubiquinone-9 in the thin slices of the liver of rats was studied during altitude adaptation. There was a three-fold acceleration of ubiquinone biosynthesis during the first period of altitude adaptation. Acceleration of biosynthesis of ubiquinone-9 in rat liver was insignificant after two weeks of adaptation. The content of ubiquinone-9 in rat liver changed but insignificantly in the course of one month of altitude adaptation.", "contents": "[The concentration and bisynthesis of ubiquinone-9 in the liver of white rats adapted to altitude hypoxia]. The content and biosynthesis of ubiquinone-9 in the thin slices of the liver of rats was studied during altitude adaptation. There was a three-fold acceleration of ubiquinone biosynthesis during the first period of altitude adaptation. Acceleration of biosynthesis of ubiquinone-9 in rat liver was insignificant after two weeks of adaptation. The content of ubiquinone-9 in rat liver changed but insignificantly in the course of one month of altitude adaptation."} {"id": "PMID:1276411", "title": "[Hepatic and myocardial glucokinase, hexokinase and glucose-6-phosphate dehydrogenase activity in rabbits with pyrogenal fever].", "content": "The activity of glucokinase, hexokinase and glucose-6- phosphoric dehydrogenase of the liver and myocardium of rabbits was tested at different stages of pyrogenal fever with the aid of spectrophotometry. A marked decrease in the activity of the enzymes under study was observed in fever. After the subsidence of fever the activity of the enzymes became normal.", "contents": "[Hepatic and myocardial glucokinase, hexokinase and glucose-6-phosphate dehydrogenase activity in rabbits with pyrogenal fever]. The activity of glucokinase, hexokinase and glucose-6- phosphoric dehydrogenase of the liver and myocardium of rabbits was tested at different stages of pyrogenal fever with the aid of spectrophotometry. A marked decrease in the activity of the enzymes under study was observed in fever. After the subsidence of fever the activity of the enzymes became normal."} {"id": "PMID:1276412", "title": "[Protein biosynthesis in the fibrillating perfused heart during normal oxygenation and following anoxia].", "content": "Methionine incorporation into proteins of the fibrillating dog heart perfused by donor circulation was investigated. In the heart in which fibrillation was induced by electric current under conditions of adequate oxygen supply a 50-55% increase of methionine S35 incorporation into the contractile protein fraction of both ventricles was observed. In the heart in which fibrillation appeared after anoxia, methionine S35 incorporation into the sum total proteins of the atria showed 40-60% depression, into the sarcoplasmic - 36 -53%, and into the contractile proteins of both ventricles - 18 -30% decrease.", "contents": "[Protein biosynthesis in the fibrillating perfused heart during normal oxygenation and following anoxia]. Methionine incorporation into proteins of the fibrillating dog heart perfused by donor circulation was investigated. In the heart in which fibrillation was induced by electric current under conditions of adequate oxygen supply a 50-55% increase of methionine S35 incorporation into the contractile protein fraction of both ventricles was observed. In the heart in which fibrillation appeared after anoxia, methionine S35 incorporation into the sum total proteins of the atria showed 40-60% depression, into the sarcoplasmic - 36 -53%, and into the contractile proteins of both ventricles - 18 -30% decrease."} {"id": "PMID:1276413", "title": "[The influence of rabies immunization of gamma-aminobutyric acid metabolism in the brains of animals].", "content": "Subcutaneous injection to albino rats (100-120 g) of lived fixed rabies virus was accompanied by a brief marked decrease in the content of gamma-aminobutryic acid in the animals' brain. There was also an increase in the activity of gamma-aminobutyric acid alpha-ketoglutaric acid transaminase in the brain tissue of animals vaccinated with live fixed rabies virus.", "contents": "[The influence of rabies immunization of gamma-aminobutyric acid metabolism in the brains of animals]. Subcutaneous injection to albino rats (100-120 g) of lived fixed rabies virus was accompanied by a brief marked decrease in the content of gamma-aminobutryic acid in the animals' brain. There was also an increase in the activity of gamma-aminobutyric acid alpha-ketoglutaric acid transaminase in the brain tissue of animals vaccinated with live fixed rabies virus."} {"id": "PMID:1276414", "title": "[The effect of long-term nitrazepam administration on sleep cycles in rats].", "content": "Single and chronic administration of a low dose of nitrazepam (1 mg/kg) had no effect on sleep cycles in rats. A single injection of a high dose (10 mg/kg) of nitrazepam resulted in prolongation of the total duration of synchronized sleep with a corresponding shortening of desynchronized (paradoxical) sleep. The number of sleep cycles was reduced. Chronic injections of nitrazepam (for 7-14 days) in a dose of 10 mg/kg evoked a gradual prolongation of the duration of paradoxical sleep and an increase in number of sleep cycles. After discontinuance of a long-term administration of nitrazepam (1 mg/kg or 10 mg/kg) prolongation of desynchronized sleep and an increase in the number of sleep cycles were more pronounced in comparison with the last day of chronic administration of the drug.", "contents": "[The effect of long-term nitrazepam administration on sleep cycles in rats]. Single and chronic administration of a low dose of nitrazepam (1 mg/kg) had no effect on sleep cycles in rats. A single injection of a high dose (10 mg/kg) of nitrazepam resulted in prolongation of the total duration of synchronized sleep with a corresponding shortening of desynchronized (paradoxical) sleep. The number of sleep cycles was reduced. Chronic injections of nitrazepam (for 7-14 days) in a dose of 10 mg/kg evoked a gradual prolongation of the duration of paradoxical sleep and an increase in number of sleep cycles. After discontinuance of a long-term administration of nitrazepam (1 mg/kg or 10 mg/kg) prolongation of desynchronized sleep and an increase in the number of sleep cycles were more pronounced in comparison with the last day of chronic administration of the drug."} {"id": "PMID:1276415", "title": "[Correlation analysis in studying the mechanism of action of smooth muscle stimulants].", "content": "The presence of correlation between the value of the maximal effects of acetylcholine and other cholinomimetics, as well as serotonin, barium chloride and depolarizing solution was studied on an isolated strip of rat stomach. It was shown that the effect of acetylcholine closely correlated with the effects of other cholinomimetics, to a lesser degree with the effects of barium chloride and depolarizing solution, and least of all with the effect of serotonin. It is proposed to use the degree of this correlation to analyze the point of action of different drugs and processes of coupling the receptor stimulation with the observed effect. It was shown that the point of convergence of the ways of coupling of the three latter influences preceded the convergence of their common way with the way of coupling of the cholinomimetic effects.", "contents": "[Correlation analysis in studying the mechanism of action of smooth muscle stimulants]. The presence of correlation between the value of the maximal effects of acetylcholine and other cholinomimetics, as well as serotonin, barium chloride and depolarizing solution was studied on an isolated strip of rat stomach. It was shown that the effect of acetylcholine closely correlated with the effects of other cholinomimetics, to a lesser degree with the effects of barium chloride and depolarizing solution, and least of all with the effect of serotonin. It is proposed to use the degree of this correlation to analyze the point of action of different drugs and processes of coupling the receptor stimulation with the observed effect. It was shown that the point of convergence of the ways of coupling of the three latter influences preceded the convergence of their common way with the way of coupling of the cholinomimetic effects."} {"id": "PMID:1276416", "title": "[The influence of the thermal factor on the antigenic properties of skin].", "content": "Results of immunochemical studies of normal and thermally-treated human skin in vitro showed at least 2 of 4-5 organospecific dermal antigens to be thermostable-they withstood heating at 100 degrees C for 3 minutes; 2 or 3 antigens were thermolabile. The thermostable antigens possessed electrophoretic migration in the field of alpha1- and gamma-globulins. The burn eschar was found to retain one of the two thermostable oranospecific antigens together with the loss of thermolabile antigen.", "contents": "[The influence of the thermal factor on the antigenic properties of skin]. Results of immunochemical studies of normal and thermally-treated human skin in vitro showed at least 2 of 4-5 organospecific dermal antigens to be thermostable-they withstood heating at 100 degrees C for 3 minutes; 2 or 3 antigens were thermolabile. The thermostable antigens possessed electrophoretic migration in the field of alpha1- and gamma-globulins. The burn eschar was found to retain one of the two thermostable oranospecific antigens together with the loss of thermolabile antigen."} {"id": "PMID:1276418", "title": "[The effect of specific sensitization and corticosteroid hormones on the course of experimental antimycotic infection].", "content": "Infection of mice and rats with actinomycetes against the background of hydrocortisone administration led to acute actinosepsis of animals to actinomycetes or extracellularly-secreted products of microbial activity contributed to the transformation of an acute infectious process into chronic, with the formation of actinomycetes hyphae in the organs. Chronic actinomycosis courses in the presence of the circulating antibodies mainly against the extracellularly-secreted products of actinomycetes vital activity.", "contents": "[The effect of specific sensitization and corticosteroid hormones on the course of experimental antimycotic infection]. Infection of mice and rats with actinomycetes against the background of hydrocortisone administration led to acute actinosepsis of animals to actinomycetes or extracellularly-secreted products of microbial activity contributed to the transformation of an acute infectious process into chronic, with the formation of actinomycetes hyphae in the organs. Chronic actinomycosis courses in the presence of the circulating antibodies mainly against the extracellularly-secreted products of actinomycetes vital activity."} {"id": "PMID:1276419", "title": "[Changes in resistance to the tumor process subserved by the presence of a focus of tuberculosis mycobacteria in the lungs].", "content": "Tumours were induced in rats with the aid of 20-methylcholantrene. Preliminary (11 to 13 days before) administration into the lung tissue of Mycobacteria tuberculosis in the composition of the water-oil emulsion decreased the animal resistance to the tumour origination. This effect is supposed to be caused by an intensification of the autoimmune processes as a result of mycobacteria administration.", "contents": "[Changes in resistance to the tumor process subserved by the presence of a focus of tuberculosis mycobacteria in the lungs]. Tumours were induced in rats with the aid of 20-methylcholantrene. Preliminary (11 to 13 days before) administration into the lung tissue of Mycobacteria tuberculosis in the composition of the water-oil emulsion decreased the animal resistance to the tumour origination. This effect is supposed to be caused by an intensification of the autoimmune processes as a result of mycobacteria administration."} {"id": "PMID:1276420", "title": "[The sensitivity of human melanoma heterotransplants to chemotherapeutic action].", "content": "There were revealed considerable individual differences in the sensitivity of human melanomas cultivated in diffusion chambers in the abdominal cavity of mice and the explants into the cheek pouches of Cricetus auratus W. to the combined action of three drugs: vincristin (or vinblastin), nitrosomethylurea, and dactinomycin. In comparing the results obtained in these two variants of investigations they proved to coincide in 3 of 5 cases. In 2 cases a negative result obtained in experimentas with Cricetus auratus W. corresponded to the positive result in experiments with diffuse chambers.", "contents": "[The sensitivity of human melanoma heterotransplants to chemotherapeutic action]. There were revealed considerable individual differences in the sensitivity of human melanomas cultivated in diffusion chambers in the abdominal cavity of mice and the explants into the cheek pouches of Cricetus auratus W. to the combined action of three drugs: vincristin (or vinblastin), nitrosomethylurea, and dactinomycin. In comparing the results obtained in these two variants of investigations they proved to coincide in 3 of 5 cases. In 2 cases a negative result obtained in experimentas with Cricetus auratus W. corresponded to the positive result in experiments with diffuse chambers."} {"id": "PMID:1276421", "title": "[Circadian rhythm of the mitotic activity of pulmonary interalveolar septum cells in rats of different ages].", "content": "The daily rhythm of mitotic activity in the lungs of the 20-day-dd embryo coincides with the rhythm of the adult organism. The mitotic activity of the 1-, 3- and 10-day-old animals was the maximum in the evening and the minimum-in the morning hours. A definitive rhythm of cells division (with the maximal mitotic activity in the morning and the minimal-in the evening) is established beginning from the 17th day of the postnatal development. The average mitotic activity is very high in the embryos, but it falls immediately after birth. It rises on the 3rd day, and begins to decrease again from the 7th day after birth.", "contents": "[Circadian rhythm of the mitotic activity of pulmonary interalveolar septum cells in rats of different ages]. The daily rhythm of mitotic activity in the lungs of the 20-day-dd embryo coincides with the rhythm of the adult organism. The mitotic activity of the 1-, 3- and 10-day-old animals was the maximum in the evening and the minimum-in the morning hours. A definitive rhythm of cells division (with the maximal mitotic activity in the morning and the minimal-in the evening) is established beginning from the 17th day of the postnatal development. The average mitotic activity is very high in the embryos, but it falls immediately after birth. It rises on the 3rd day, and begins to decrease again from the 7th day after birth."} {"id": "PMID:1276422", "title": "[Circadian rhythms in connective tissue].", "content": "A study of circadian rhythms in the connective tissue showed cell elements (particularly histiocytes) to be characterized by circadian rhythms of the metabolic processes. This is expressed in a distinct diurnal activity of the succinic dehydrogenase (SDH) and lactic dehydrogenase (LDH). In the processes of adaptation to the high altitude hypoxia the activity of SDH and LDH was higher than in control, but dynamics of the changes of their activity repeated the changes in control group. It is concluded that circadian rhythms of the metabolic processes in the connective tissue were sufficiently stable: no visible changes were observed during adaptation to high altitudes.", "contents": "[Circadian rhythms in connective tissue]. A study of circadian rhythms in the connective tissue showed cell elements (particularly histiocytes) to be characterized by circadian rhythms of the metabolic processes. This is expressed in a distinct diurnal activity of the succinic dehydrogenase (SDH) and lactic dehydrogenase (LDH). In the processes of adaptation to the high altitude hypoxia the activity of SDH and LDH was higher than in control, but dynamics of the changes of their activity repeated the changes in control group. It is concluded that circadian rhythms of the metabolic processes in the connective tissue were sufficiently stable: no visible changes were observed during adaptation to high altitudes."} {"id": "PMID:1276423", "title": "[Physiologic regeneration of jejunal epithelium following bilateral subdiaphragmatic vagotomy in rats].", "content": "Seven days after vagotomy in rats there was an increase of the mitotic activity of the epithelium of the small intestine; this index was about 1.5 greater in the experimental ats in comparison with control animals. Daily rhythm of the mitotic activity was constant under these conditions, but the amplitude of daily fluctuations was levelled. Vagotomy failed to alter the stable regimen of renovation of the cell population of the \"crypt-villus\" system.", "contents": "[Physiologic regeneration of jejunal epithelium following bilateral subdiaphragmatic vagotomy in rats]. Seven days after vagotomy in rats there was an increase of the mitotic activity of the epithelium of the small intestine; this index was about 1.5 greater in the experimental ats in comparison with control animals. Daily rhythm of the mitotic activity was constant under these conditions, but the amplitude of daily fluctuations was levelled. Vagotomy failed to alter the stable regimen of renovation of the cell population of the \"crypt-villus\" system."} {"id": "PMID:1276424", "title": "[Changes in the mitotic regime of a cell culture under the influence of sensitins].", "content": "A study of the effect of three types of lyophilized sensitin preparations on cell culture of human amnion showed an increase in the amount of pathological mitoses, arrest of division at the metaphase and the appearance of chromosome adhesions absent in the control culture. These changes pointed to destructive action of the preparations under consideration on chromosomes and achromatine spindle, and from the author's point of view, characterized toxic properties of sensitin.", "contents": "[Changes in the mitotic regime of a cell culture under the influence of sensitins]. A study of the effect of three types of lyophilized sensitin preparations on cell culture of human amnion showed an increase in the amount of pathological mitoses, arrest of division at the metaphase and the appearance of chromosome adhesions absent in the control culture. These changes pointed to destructive action of the preparations under consideration on chromosomes and achromatine spindle, and from the author's point of view, characterized toxic properties of sensitin."} {"id": "PMID:1276425", "title": "[Self-maintenance of induced bone tissue].", "content": "The capacity for self-maintenance of the bone marrow osteogenic precursor cells from the skeletal bones and from the bones induced by implantation of decalcified bone matrix is compared. Transplantation in diffusion chambers is employed as the test system. Osteogenesis in the bone marrow transplants isolated from the skeletal bone lasts several months, whereas osteogenesis in the bone marrow transplants isolated from induced bone stops after the second month. Fibroblasts arising in the monolayer cultures of the skeletal bone marrow retained their osteogenic potencies after repeated passages. On the contrary, fibroblasts from the monolayer cultures of induced bone marrow lost their osteogenic capacity after the second passage. Thus, contrary to osteogenic precursors of the skeletal bone, osteogenic precursors of induced bone tissue had a very limited self-maintaining capacity after the cessation of induction.", "contents": "[Self-maintenance of induced bone tissue]. The capacity for self-maintenance of the bone marrow osteogenic precursor cells from the skeletal bones and from the bones induced by implantation of decalcified bone matrix is compared. Transplantation in diffusion chambers is employed as the test system. Osteogenesis in the bone marrow transplants isolated from the skeletal bone lasts several months, whereas osteogenesis in the bone marrow transplants isolated from induced bone stops after the second month. Fibroblasts arising in the monolayer cultures of the skeletal bone marrow retained their osteogenic potencies after repeated passages. On the contrary, fibroblasts from the monolayer cultures of induced bone marrow lost their osteogenic capacity after the second passage. Thus, contrary to osteogenic precursors of the skeletal bone, osteogenic precursors of induced bone tissue had a very limited self-maintaining capacity after the cessation of induction."} {"id": "PMID:1276426", "title": "[A cytochemical study of binaurally converging connections in the nuclei of the cat superior olive].", "content": "Experiments of binaurally converging connections on the level of the superior olive nuclei was carried out on anesthetized cats by the method of quantitative cytospectrometry. A considerable increase in the cytoplasmic RNA content in the neurons of the ipsi- and contralateral medial and lateral nuclei was observed following a 2-hour monaural stimulation by rhythmical sound (noise) signals. The volume of the functioning neurons of the nuclei under study showed either no significant change or increased. The data obtained demonstrated the nature of functional organization of the binaurally converging connections.", "contents": "[A cytochemical study of binaurally converging connections in the nuclei of the cat superior olive]. Experiments of binaurally converging connections on the level of the superior olive nuclei was carried out on anesthetized cats by the method of quantitative cytospectrometry. A considerable increase in the cytoplasmic RNA content in the neurons of the ipsi- and contralateral medial and lateral nuclei was observed following a 2-hour monaural stimulation by rhythmical sound (noise) signals. The volume of the functioning neurons of the nuclei under study showed either no significant change or increased. The data obtained demonstrated the nature of functional organization of the binaurally converging connections."} {"id": "PMID:1276427", "title": "[Effector innervation of melanophores of the arteries of the base of the brain].", "content": "Melanophores in the arteries of the base of the brain of kittens displayed pronounced variations in size and shape in response to the peripheral electrical stimulation of the vagus and the sympathetic nerves. These melanophores changed their size and shape under the influence of acetylcholine and noradrenaline solutions in vitro too. The present experiments showed melanophores to have a double effector innervation.", "contents": "[Effector innervation of melanophores of the arteries of the base of the brain]. Melanophores in the arteries of the base of the brain of kittens displayed pronounced variations in size and shape in response to the peripheral electrical stimulation of the vagus and the sympathetic nerves. These melanophores changed their size and shape under the influence of acetylcholine and noradrenaline solutions in vitro too. The present experiments showed melanophores to have a double effector innervation."} {"id": "PMID:1276428", "title": "[The vesicular system of the endothelium in the blood-carrying capillaries of the diaphragm with different functional states].", "content": "Micropinocytotic vesicles were counted in the endothelial cells of blood capillaries in the muscle of the diaphragm in its indirect rhythmic stimulation at a frequency of 50 imp/s after section of the phrenic nerve, and also in natural contraction and relaxation of the muscle during respiration. A change in the total count of the vesicles and even more pronounced changes in the ratio of the vesicles bound with plasmic membranes and freely located in the cytoplasm of the cells were revealed; this pointed to the change in the transendothelial transfer of substances. It appeared that the state of the process of vesicle formation could influence the method of fixation applied.", "contents": "[The vesicular system of the endothelium in the blood-carrying capillaries of the diaphragm with different functional states]. Micropinocytotic vesicles were counted in the endothelial cells of blood capillaries in the muscle of the diaphragm in its indirect rhythmic stimulation at a frequency of 50 imp/s after section of the phrenic nerve, and also in natural contraction and relaxation of the muscle during respiration. A change in the total count of the vesicles and even more pronounced changes in the ratio of the vesicles bound with plasmic membranes and freely located in the cytoplasm of the cells were revealed; this pointed to the change in the transendothelial transfer of substances. It appeared that the state of the process of vesicle formation could influence the method of fixation applied."} {"id": "PMID:1276429", "title": "[Metabolic disorders and plasmorrhagia in myocardial cells following adrenalin damage].", "content": "The authors examined serial sections of the myocardium of rats sacrificed at periods of from 1 to 24 hours after adrenalin administration. The results of histoenzymatic reaction to succinic dehydrogenase (a test for cell injury) were compared with the data obtained in fibrin detection by Coons' method. Plasmorrhagia into the irreversibly injured muscle cells had a characteristic appearance in the test with nitro-BT; there proved to be no fibrin in the fibers with fatty dystrophy marked by macrogranular depositions of formazan. A supposition was put forward on different pathogenesis of the reversible and irreversible injuries of the myocardium caused by adrenalin administration.", "contents": "[Metabolic disorders and plasmorrhagia in myocardial cells following adrenalin damage]. The authors examined serial sections of the myocardium of rats sacrificed at periods of from 1 to 24 hours after adrenalin administration. The results of histoenzymatic reaction to succinic dehydrogenase (a test for cell injury) were compared with the data obtained in fibrin detection by Coons' method. Plasmorrhagia into the irreversibly injured muscle cells had a characteristic appearance in the test with nitro-BT; there proved to be no fibrin in the fibers with fatty dystrophy marked by macrogranular depositions of formazan. A supposition was put forward on different pathogenesis of the reversible and irreversible injuries of the myocardium caused by adrenalin administration."} {"id": "PMID:1276431", "title": "[Electrophysiological analysis of the effect of cortisone on the rat neuromuscular apparatus].", "content": "The influence of cortisone (1.5 mg per 100 g of body weight, daily, for 10 days) on the neuro-muscular system was studied in rats in situ. The action potentials of the nerve and muscle were recorded with the extracellular electrodes. The rest potentials (RP) of the muscle fibers and the miniature end-plate potentials (MEPP) were recorded with the intracellular glass microelectrodes. A decrease of the RP and the MEPP amplitude, and an increase of the MEPP frequency and prolongation of the neuromuscular transmission time were revealed in rats given daily doses of cortisone, 1.5 mg/100 g of body weight, during 10 days; reliability of the neuro-muscular transmission (acceleration of the fall of the muscle action potential amplitude during tetanus) proved to decrease under the action of cortisone.", "contents": "[Electrophysiological analysis of the effect of cortisone on the rat neuromuscular apparatus]. The influence of cortisone (1.5 mg per 100 g of body weight, daily, for 10 days) on the neuro-muscular system was studied in rats in situ. The action potentials of the nerve and muscle were recorded with the extracellular electrodes. The rest potentials (RP) of the muscle fibers and the miniature end-plate potentials (MEPP) were recorded with the intracellular glass microelectrodes. A decrease of the RP and the MEPP amplitude, and an increase of the MEPP frequency and prolongation of the neuromuscular transmission time were revealed in rats given daily doses of cortisone, 1.5 mg/100 g of body weight, during 10 days; reliability of the neuro-muscular transmission (acceleration of the fall of the muscle action potential amplitude during tetanus) proved to decrease under the action of cortisone."} {"id": "PMID:1276432", "title": "[Urea and amino acid transport by an isolated human placenta].", "content": "A method of bilateral perfusion of the isolated human placenta was used to study the urea transport from the fetal placental stream into the maternal one, and of amino acid transport in the opposite direction. Experiments demonstrated that the method provided a sufficiently full perfusion of the intervillous space and offered possibilities for studying the placental transport. With equal amino nitrogen concentration in both circulations, its content in the fetal stream increased during the experiment. This elevation was more expressed when amino acid was added to the maternal circulation. The idea of amino acid \"secretion\" by the trophoblast cell elements into the fetal circulation was confirmed by the above experiments.", "contents": "[Urea and amino acid transport by an isolated human placenta]. A method of bilateral perfusion of the isolated human placenta was used to study the urea transport from the fetal placental stream into the maternal one, and of amino acid transport in the opposite direction. Experiments demonstrated that the method provided a sufficiently full perfusion of the intervillous space and offered possibilities for studying the placental transport. With equal amino nitrogen concentration in both circulations, its content in the fetal stream increased during the experiment. This elevation was more expressed when amino acid was added to the maternal circulation. The idea of amino acid \"secretion\" by the trophoblast cell elements into the fetal circulation was confirmed by the above experiments."} {"id": "PMID:1276433", "title": "[Participation of adrenal hormones in the genesis of arterial hypertension of hypothalamic origin].", "content": "Continuous many-hour stimulation of the hypothalamic negative emotiogenic centres (ventromedial nuclei) evoked a stable arterial hypertension with a peculiar phasic dynamics of the adrenal secretory activity in waking immobilized rabbits. Bilateral extirpation of the adrenal glands decreased the initial level of the average arterial pressure, inhibiting development of stable arterial hypertension. Many-hour stimulation of the mentioned structures also produced stable arterial hypertension in adrenalectomized rabbits if preceded by the administration of hydrocortisone together with adrenaline. Against the background of separate administration of hydrocortisone and adrenaline to adrenalectomized rabbits, many-hour stimulation of the ventromedial hypothalamus evoked a short-term rise in the arterial pressure. A conclusion was drawn that activation of hormones of the adrenal cortical and medullary layers played an important part in the formation of stable arterial hypertension in rabbits under continuous many-hour stimulation of the hypothalamic negative emotiogenic centres.", "contents": "[Participation of adrenal hormones in the genesis of arterial hypertension of hypothalamic origin]. Continuous many-hour stimulation of the hypothalamic negative emotiogenic centres (ventromedial nuclei) evoked a stable arterial hypertension with a peculiar phasic dynamics of the adrenal secretory activity in waking immobilized rabbits. Bilateral extirpation of the adrenal glands decreased the initial level of the average arterial pressure, inhibiting development of stable arterial hypertension. Many-hour stimulation of the mentioned structures also produced stable arterial hypertension in adrenalectomized rabbits if preceded by the administration of hydrocortisone together with adrenaline. Against the background of separate administration of hydrocortisone and adrenaline to adrenalectomized rabbits, many-hour stimulation of the ventromedial hypothalamus evoked a short-term rise in the arterial pressure. A conclusion was drawn that activation of hormones of the adrenal cortical and medullary layers played an important part in the formation of stable arterial hypertension in rabbits under continuous many-hour stimulation of the hypothalamic negative emotiogenic centres."} {"id": "PMID:1276434", "title": "[Tissue respiration of rat internal organs and skin during prolonged exposure to high ambient temperature].", "content": "Oxygen consumption by tissues of various organs was studied in acute experiments on albino rats in Warburg apparatus at a temperature of 37 degrees C. High environmental temperature proved to decrease the tissue gas exchange level. Participation of different organs in the reduction of total metabolic level varied and depended on the number of actions of the thermal factor. A more active inclusion of the majority of the organs into the adaptive reactions of the organism to the high temperature occurred during the third week.", "contents": "[Tissue respiration of rat internal organs and skin during prolonged exposure to high ambient temperature]. Oxygen consumption by tissues of various organs was studied in acute experiments on albino rats in Warburg apparatus at a temperature of 37 degrees C. High environmental temperature proved to decrease the tissue gas exchange level. Participation of different organs in the reduction of total metabolic level varied and depended on the number of actions of the thermal factor. A more active inclusion of the majority of the organs into the adaptive reactions of the organism to the high temperature occurred during the third week."} {"id": "PMID:1276435", "title": "[Hemodynamic analysis of the hypotensive effect of portacaval transposition of vessels in vasorenal hypertension].", "content": "Experiments were conducted on unanesthetized dogs; the influence of portocaval transposition on the systemic hemodynamics of the intact dogs and dogs with experimental vasorenal hypertension was studied. Arterial pressure was decreased in dogs with vasorenal hypertension after portocaval transposition mainly by means of reduction of the total peripheral resistance. There was no considerable change of hemodynamics in the intact dogs after the portocaval transposition.", "contents": "[Hemodynamic analysis of the hypotensive effect of portacaval transposition of vessels in vasorenal hypertension]. Experiments were conducted on unanesthetized dogs; the influence of portocaval transposition on the systemic hemodynamics of the intact dogs and dogs with experimental vasorenal hypertension was studied. Arterial pressure was decreased in dogs with vasorenal hypertension after portocaval transposition mainly by means of reduction of the total peripheral resistance. There was no considerable change of hemodynamics in the intact dogs after the portocaval transposition."} {"id": "PMID:1276436", "title": "[Absorptive-excretory function of isolated dog liver during its perfusion].", "content": "Twenty experiments were performed on mongrel dogs. The absorptive and excretory function of the liver in the intact organism and during its isolated perfusion through the portal vein with the use of extracorporeal circulation was studied by means of the bromsulfaline test. The absorptive function of the perfused liver proved to decrease by 50-60 per cent. The rate of bile elimination and plasma clearance was 5-6 times higher at the beginning of the experiment in the intact organism. Later on, the difference in the degree of retention of the hepatic excretory function was reduced. Hypoxia connected with denervation, hepatectomy and the isolated perfusion proper apparently served as the principal cause of reduction of the absorptive-excretory function of the isolated liver.", "contents": "[Absorptive-excretory function of isolated dog liver during its perfusion]. Twenty experiments were performed on mongrel dogs. The absorptive and excretory function of the liver in the intact organism and during its isolated perfusion through the portal vein with the use of extracorporeal circulation was studied by means of the bromsulfaline test. The absorptive function of the perfused liver proved to decrease by 50-60 per cent. The rate of bile elimination and plasma clearance was 5-6 times higher at the beginning of the experiment in the intact organism. Later on, the difference in the degree of retention of the hepatic excretory function was reduced. Hypoxia connected with denervation, hepatectomy and the isolated perfusion proper apparently served as the principal cause of reduction of the absorptive-excretory function of the isolated liver."} {"id": "PMID:1276437", "title": "[Heparin and mast cells in the dynamics of experimental extrahepatic cholestasis].", "content": "The content of heparin in the blood and mast cell count in rat tissues were studied during different periods of experimental extrahepatic cholestasis induced in rats by ligation of the common bile duct. During cholestasis the blood heparin level proved to increase and the mast cell count fell on the 3rd day, increased on the 7th day and fell again on the 14th day. Correlation between the degranulated and nondegranulated forms of mast cells altered in favour of the latter. The fluctuation of mast cell counts and increase of degranulated forms is considered to be the best result of mast cell irritation produced by bile acids and pigments which accumulated in the organism.", "contents": "[Heparin and mast cells in the dynamics of experimental extrahepatic cholestasis]. The content of heparin in the blood and mast cell count in rat tissues were studied during different periods of experimental extrahepatic cholestasis induced in rats by ligation of the common bile duct. During cholestasis the blood heparin level proved to increase and the mast cell count fell on the 3rd day, increased on the 7th day and fell again on the 14th day. Correlation between the degranulated and nondegranulated forms of mast cells altered in favour of the latter. The fluctuation of mast cell counts and increase of degranulated forms is considered to be the best result of mast cell irritation produced by bile acids and pigments which accumulated in the organism."} {"id": "PMID:1276438", "title": "[Use of DNA in cytopenia induced by myelosan].", "content": "Wistar rats weighing 180-190 g received myleran per os in a single dose of 10 mg/kg, or fractionally (total dose of 25 mg/kg) for 18 days. After myleran administration the animals were injected 4-5 times (every other day) with a homologous DNA in a dose of 2 mg per rat or with a standard salt citrate. The DNA injection reduced the duration of leukopenia. With the least dose of myleran leukocyte count returned to the normal in 6 days in the treated animals and in 25 days in the untreated controls and with the highest dose -- in 15 and in 25 days, respectively, from the beginning of the treatment. The differences in the leukocyte count between the treated and control rats in both experiments were mainly due to the dynamics of neutrophils, the content of which in the treated animals exceeded that in the untreated animals by 54-110% in the course of 6-15 days in the first, and by 23-38% in the course of 10-23 days in the second experiment.", "contents": "[Use of DNA in cytopenia induced by myelosan]. Wistar rats weighing 180-190 g received myleran per os in a single dose of 10 mg/kg, or fractionally (total dose of 25 mg/kg) for 18 days. After myleran administration the animals were injected 4-5 times (every other day) with a homologous DNA in a dose of 2 mg per rat or with a standard salt citrate. The DNA injection reduced the duration of leukopenia. With the least dose of myleran leukocyte count returned to the normal in 6 days in the treated animals and in 25 days in the untreated controls and with the highest dose -- in 15 and in 25 days, respectively, from the beginning of the treatment. The differences in the leukocyte count between the treated and control rats in both experiments were mainly due to the dynamics of neutrophils, the content of which in the treated animals exceeded that in the untreated animals by 54-110% in the course of 6-15 days in the first, and by 23-38% in the course of 10-23 days in the second experiment."} {"id": "PMID:1276439", "title": "[Regulation of mitochondrial membrane permeability by a factor from mitochondrial interaction].", "content": "It was shown that a factor from the thyroxine-injured mitochondria caused inhibition of mitochondrial swelling in isotonic KNO3 and NH4NO3 solutions in the presence of rotenone. These data were interpreted as permeability inhibition for K+ and H+ ions.", "contents": "[Regulation of mitochondrial membrane permeability by a factor from mitochondrial interaction]. It was shown that a factor from the thyroxine-injured mitochondria caused inhibition of mitochondrial swelling in isotonic KNO3 and NH4NO3 solutions in the presence of rotenone. These data were interpreted as permeability inhibition for K+ and H+ ions."} {"id": "PMID:1276440", "title": "[Change in the content of ATP and 2,3-diphosphoglycerate in the erythrocytes of rats adapted to hypoxia].", "content": "It was shown that on the 30th-60th days of training rats to hypoxia under conditions of pressure chamber there was an increase in ATP and 2,3-diphosphoglycerate content in erythrocytes. By changing the affinity of hemoglobin to oxygen the mentioned shifts could play an important role in the improvement of oxygen supply to the tissues.", "contents": "[Change in the content of ATP and 2,3-diphosphoglycerate in the erythrocytes of rats adapted to hypoxia]. It was shown that on the 30th-60th days of training rats to hypoxia under conditions of pressure chamber there was an increase in ATP and 2,3-diphosphoglycerate content in erythrocytes. By changing the affinity of hemoglobin to oxygen the mentioned shifts could play an important role in the improvement of oxygen supply to the tissues."} {"id": "PMID:1276441", "title": "[Induction of liver microsomal monoxygenases in experimental cholestasis].", "content": "The dependence of expressiveness of microsomal mono-oxygenase induction by phenobarbital upon the amount of binding sites at cytochrome P-450 active center(s) has been studied. The experimental cholestasis is accompanied by accumulation of hydroxylated derivatives of cholesterol, which possess the detergent characteristics and destruct the substrate binding sites in P-450 molecule. The possibility has been demonstrated of phenobarbital induction under conditions when the inducer-monooxygenase primary binding and metabolic steps are not involved. It is assumed that the activation of de novo microsomal protein synthesis is effected by the molecule of phenobarbital itself and not by the products of its primary hydroxylation in the microsomes.", "contents": "[Induction of liver microsomal monoxygenases in experimental cholestasis]. The dependence of expressiveness of microsomal mono-oxygenase induction by phenobarbital upon the amount of binding sites at cytochrome P-450 active center(s) has been studied. The experimental cholestasis is accompanied by accumulation of hydroxylated derivatives of cholesterol, which possess the detergent characteristics and destruct the substrate binding sites in P-450 molecule. The possibility has been demonstrated of phenobarbital induction under conditions when the inducer-monooxygenase primary binding and metabolic steps are not involved. It is assumed that the activation of de novo microsomal protein synthesis is effected by the molecule of phenobarbital itself and not by the products of its primary hydroxylation in the microsomes."} {"id": "PMID:1276442", "title": "[Participation of thyroid hormones in realization of the action of diphtheria toxin on oxidative phosphorylation in rabbit liver mitochondria].", "content": "Experiments were conducted on rats with an experimental hypo- and hyperthyroidism. In hypothyroidism there was no disturbance of the capacity to phosphorylation conjugated with respiration in the mitochondria from the liver in intravenous injection of diphtheria toxin, but in hyperthyroidism sensitivity of mitochondria of the liver to the uncoupling action of diphtheria toxin was much increased. It is supposed that of great significance for the uncoupling action of diphtheria toxin on the oxidative phosphorylation was the incretory function of the thyroid gland.", "contents": "[Participation of thyroid hormones in realization of the action of diphtheria toxin on oxidative phosphorylation in rabbit liver mitochondria]. Experiments were conducted on rats with an experimental hypo- and hyperthyroidism. In hypothyroidism there was no disturbance of the capacity to phosphorylation conjugated with respiration in the mitochondria from the liver in intravenous injection of diphtheria toxin, but in hyperthyroidism sensitivity of mitochondria of the liver to the uncoupling action of diphtheria toxin was much increased. It is supposed that of great significance for the uncoupling action of diphtheria toxin on the oxidative phosphorylation was the incretory function of the thyroid gland."} {"id": "PMID:1276443", "title": "[Physicochemical changes in DNA and deoxyribonucleoprotein caused by potassium cyanate].", "content": "The influence of KNCO on the structural integrity of the DNP salt solutions was studied. By the methods of sedimentation, viscosimetry, spectrophotometry and circular dichroism it was shown that KNCO failed to induce degrading the polynucleotide DNA strands and weakened the bonds between the DNA and protein.", "contents": "[Physicochemical changes in DNA and deoxyribonucleoprotein caused by potassium cyanate]. The influence of KNCO on the structural integrity of the DNP salt solutions was studied. By the methods of sedimentation, viscosimetry, spectrophotometry and circular dichroism it was shown that KNCO failed to induce degrading the polynucleotide DNA strands and weakened the bonds between the DNA and protein."} {"id": "PMID:1276444", "title": "[Increase in the concentration of RNA in the blood erythrocytes of women in the ovulation period].", "content": "It was revealed that there was an increase (by an average of 58%) of the RNA concentration in the blood erythrocytes of women during ovulation. Measurement of the RNA content in erythrocytes can serve as an ovulation test.", "contents": "[Increase in the concentration of RNA in the blood erythrocytes of women in the ovulation period]. It was revealed that there was an increase (by an average of 58%) of the RNA concentration in the blood erythrocytes of women during ovulation. Measurement of the RNA content in erythrocytes can serve as an ovulation test."} {"id": "PMID:1276445", "title": "[Adenylate cyclase activity in human nasal polyps under conditions of stimulation of serotonin biosynthesis (in vitro)].", "content": "Nasal polyp tissue possess adenylatecyclase activity. Under conditions of incubation of nasal polyps with the use of reserpine (an activator of serotonin synthesis in this tissue) there can be observed a statistically significant increase of adenylatecyclase activity. During the first minutes of the polyp incubation with reserpine the activity of the enzyme rose ten-fold. Participation of the adenylatecyclase system at the initial stages of morphological and biochemical differentiation, accompanying serotonin biosynthesis in human nose polyps was confirmed.", "contents": "[Adenylate cyclase activity in human nasal polyps under conditions of stimulation of serotonin biosynthesis (in vitro)]. Nasal polyp tissue possess adenylatecyclase activity. Under conditions of incubation of nasal polyps with the use of reserpine (an activator of serotonin synthesis in this tissue) there can be observed a statistically significant increase of adenylatecyclase activity. During the first minutes of the polyp incubation with reserpine the activity of the enzyme rose ten-fold. Participation of the adenylatecyclase system at the initial stages of morphological and biochemical differentiation, accompanying serotonin biosynthesis in human nose polyps was confirmed."} {"id": "PMID:1276446", "title": "[Effect of blood serum from schizophrenic patients and from normal donors on DNA synthesis in lymphocytes].", "content": "The number of DNA-synthesizing lymphocytes in the phytohemagglutinin (PHA)-stimulated cultures of the peripheral blood of schizophrenic patients was determined. Under the mentioned conditions the number of DNA-synthesizing lymphocytes of the schizophrenic patients was 18% less than in the cultures of healthy donors. When the PHA-treated lymphocytes of normal donors were incubated with the serum of schizophrenic patients the number of lymphocytes capable of synthesizing DNA in the presence of PHA fell by 21%.", "contents": "[Effect of blood serum from schizophrenic patients and from normal donors on DNA synthesis in lymphocytes]. The number of DNA-synthesizing lymphocytes in the phytohemagglutinin (PHA)-stimulated cultures of the peripheral blood of schizophrenic patients was determined. Under the mentioned conditions the number of DNA-synthesizing lymphocytes of the schizophrenic patients was 18% less than in the cultures of healthy donors. When the PHA-treated lymphocytes of normal donors were incubated with the serum of schizophrenic patients the number of lymphocytes capable of synthesizing DNA in the presence of PHA fell by 21%."} {"id": "PMID:1276447", "title": "[Localization and possible development cycle of mycoplasmas and bacterial L-forms in cell cultures].", "content": "Using vital stain chlorazol-black E the authors studied the localization and behaviour of 5 mycoplasma species and the stable L-form of beta-hemolytic streptococcus of group A in various continuous cell lines. Mycoplasmas and L-forms had a definite evolution cycle in the cells. At first they are arranged extracellularly and on the surface of the cells, and then intracellularly where they multiply intensively; later they are again localized on the surface of the cells and extracellularly. This cycle proved to depend on the type of infection. The character of the localization depended on the type of the causative agent and of the culture.", "contents": "[Localization and possible development cycle of mycoplasmas and bacterial L-forms in cell cultures]. Using vital stain chlorazol-black E the authors studied the localization and behaviour of 5 mycoplasma species and the stable L-form of beta-hemolytic streptococcus of group A in various continuous cell lines. Mycoplasmas and L-forms had a definite evolution cycle in the cells. At first they are arranged extracellularly and on the surface of the cells, and then intracellularly where they multiply intensively; later they are again localized on the surface of the cells and extracellularly. This cycle proved to depend on the type of infection. The character of the localization depended on the type of the causative agent and of the culture."} {"id": "PMID:1276448", "title": "[Reduction of the biological activity of Vibrio cholerae culture filtrates exposed to neuraminidase inhibitors].", "content": "Experiments were conducted on a model of edema of albino mouse paws; a study was made of the effect of neuraminidase inhibitors on the cholerogenic effect of a filtrate of cholera vibrio culture. It appeared that addition to the filtrate of inhibitors depressed its biological activity. Since no cholerogenic action was possessed by the purified neuraminidase preparations from the cholera vibrios it was suggested that there existed a chemical affinity between the region of cholerogen responsible for fixation on the cell membranes and the active neuraminidase centre.", "contents": "[Reduction of the biological activity of Vibrio cholerae culture filtrates exposed to neuraminidase inhibitors]. Experiments were conducted on a model of edema of albino mouse paws; a study was made of the effect of neuraminidase inhibitors on the cholerogenic effect of a filtrate of cholera vibrio culture. It appeared that addition to the filtrate of inhibitors depressed its biological activity. Since no cholerogenic action was possessed by the purified neuraminidase preparations from the cholera vibrios it was suggested that there existed a chemical affinity between the region of cholerogen responsible for fixation on the cell membranes and the active neuraminidase centre."} {"id": "PMID:1276449", "title": "[Analysis of water-soluble antigens of chick iris].", "content": "Three serum and twelve tissue antigens were revealed in adult chick iris by immunodiffusion and immunoelectrophoresis. Among the tissue antigens five were characteristic of the eye tissues alone: a specific iris antigen, an antigen revealed in the iris and the retina, and three antigens characteristic of the lens (the alpha-, beta- and delta-crystallines). The rest seven antigens were interorganic differing by their distribution in the tissues and organs investigated; among them one was specific of muscle tissue.", "contents": "[Analysis of water-soluble antigens of chick iris]. Three serum and twelve tissue antigens were revealed in adult chick iris by immunodiffusion and immunoelectrophoresis. Among the tissue antigens five were characteristic of the eye tissues alone: a specific iris antigen, an antigen revealed in the iris and the retina, and three antigens characteristic of the lens (the alpha-, beta- and delta-crystallines). The rest seven antigens were interorganic differing by their distribution in the tissues and organs investigated; among them one was specific of muscle tissue."} {"id": "PMID:1276450", "title": "[Study of antibodies to heterologous connective tissue, isolated from sera of patients with rheumatism].", "content": "Antibodies against connective tissue elements of various bovine organs were isolated from the sera of rheumatic fever patients with the aid of immunosorbents (bovine connective tissue extract and erythrocyte stroma). The antibody preparations obtained were not identical and contained antibodies against different antigens of bovine connective tissue. The antibody preparations failed to react with human connective tissue components.", "contents": "[Study of antibodies to heterologous connective tissue, isolated from sera of patients with rheumatism]. Antibodies against connective tissue elements of various bovine organs were isolated from the sera of rheumatic fever patients with the aid of immunosorbents (bovine connective tissue extract and erythrocyte stroma). The antibody preparations obtained were not identical and contained antibodies against different antigens of bovine connective tissue. The antibody preparations failed to react with human connective tissue components."} {"id": "PMID:1276451", "title": "[Cytotoxic action of immune lymphocytes on \"adherent\" cells (macrophages) of autologous system lymph nodes during delayed hypersensitivity].", "content": "A study was made in the autologous system of the cytotoxic action of immune lymphocytes on the \"adherent\" cells (macrophages) of the lymph nodes of guinea pigs in delayed hypersensitivity (DH) to the streptococcus antigens and tuberculoproteins. Death of a considerable number of the \"adherent\" cells in cultivation of a suspension of cells of the lymph nodes of animals sensitized with the culture of streptococcus or BCG in the presence of specific antigen (thermo-stable streptococcus fraction or tuberculin, respectively) alone. Detection of death of the \"adherent\" cells in the autologous system can be used as one of specific and sensitive tests in studying the DH.", "contents": "[Cytotoxic action of immune lymphocytes on \"adherent\" cells (macrophages) of autologous system lymph nodes during delayed hypersensitivity]. A study was made in the autologous system of the cytotoxic action of immune lymphocytes on the \"adherent\" cells (macrophages) of the lymph nodes of guinea pigs in delayed hypersensitivity (DH) to the streptococcus antigens and tuberculoproteins. Death of a considerable number of the \"adherent\" cells in cultivation of a suspension of cells of the lymph nodes of animals sensitized with the culture of streptococcus or BCG in the presence of specific antigen (thermo-stable streptococcus fraction or tuberculin, respectively) alone. Detection of death of the \"adherent\" cells in the autologous system can be used as one of specific and sensitive tests in studying the DH."} {"id": "PMID:1276452", "title": "[Carcinoembryonic antigen in rat blood serum in nonspecific intestinal disease].", "content": "Sera of rats in which an extensive injury of the caecum was inflicted were studied by precipitation in agar. The carcino-embryonic antigen appeared in the sera of 84% of the animals 24 hours after the damage, and persisted in the majority of the animals for a period of 15-20 days; this corresponded to the period of the most pronounced regeneration of the intestinal mucosa.", "contents": "[Carcinoembryonic antigen in rat blood serum in nonspecific intestinal disease]. Sera of rats in which an extensive injury of the caecum was inflicted were studied by precipitation in agar. The carcino-embryonic antigen appeared in the sera of 84% of the animals 24 hours after the damage, and persisted in the majority of the animals for a period of 15-20 days; this corresponded to the period of the most pronounced regeneration of the intestinal mucosa."} {"id": "PMID:1276453", "title": "[Change in the sensitivity to methotrexate of neoplastic cells cultivated in the presence of folic acid].", "content": "Cultivation of tumour L-cells in the presence of increasing folic acid concentrations led to the rise in the resistance of these cells population to metotrexate. With the subsequent cultivation, when the folic acid concentration was not increased the population of such cells became more sensitive to metotrexate even in comparison with the initial L-cells.", "contents": "[Change in the sensitivity to methotrexate of neoplastic cells cultivated in the presence of folic acid]. Cultivation of tumour L-cells in the presence of increasing folic acid concentrations led to the rise in the resistance of these cells population to metotrexate. With the subsequent cultivation, when the folic acid concentration was not increased the population of such cells became more sensitive to metotrexate even in comparison with the initial L-cells."} {"id": "PMID:1276454", "title": "Cloning of canine hematopoietic cells in vitro.", "content": "A modified cloning method of the agar culture of canine bone marrow cells was described. A high efficiency of colony formation was seen only after addition to the agar medium of the colony-stimulating activity (CSA) from different sources. Dog serum in a 20% concentration was used in this case. With the optimal CSA concentration there was seen a linear relationship between the number of explanted cells and the number of produced colonies. This method is suitable for determination of committed granulocyte precursor cells, as well as for the study of potential humoral regulators of granulocytopoiesis in dogs.", "contents": "Cloning of canine hematopoietic cells in vitro. A modified cloning method of the agar culture of canine bone marrow cells was described. A high efficiency of colony formation was seen only after addition to the agar medium of the colony-stimulating activity (CSA) from different sources. Dog serum in a 20% concentration was used in this case. With the optimal CSA concentration there was seen a linear relationship between the number of explanted cells and the number of produced colonies. This method is suitable for determination of committed granulocyte precursor cells, as well as for the study of potential humoral regulators of granulocytopoiesis in dogs."} {"id": "PMID:1276455", "title": "[Characteristics of liver regeneration and growth in 3-week-old mice of different strains].", "content": "Three-week mice of C57BL strain are characterized by low proliferative activity of hepatocytes during normal growth of the liver. Hepatocytes of mice of this strain also had low proliferative activity 44 hours after partial hepatectomy (16%). Mice of the same age, but of other strains (mongrel, CBA, CC57BR) had higher mitotic indices both during normal growth and during regeneration (42; 70 and 60%, respectively). This peculiarity in the mitotic activity of hepatocytes of mice of different strains was also present 7 days after the beginning of the experiment. The data obtained indicated the genetic determination of the level of proliferative activity of hepatocytes.", "contents": "[Characteristics of liver regeneration and growth in 3-week-old mice of different strains]. Three-week mice of C57BL strain are characterized by low proliferative activity of hepatocytes during normal growth of the liver. Hepatocytes of mice of this strain also had low proliferative activity 44 hours after partial hepatectomy (16%). Mice of the same age, but of other strains (mongrel, CBA, CC57BR) had higher mitotic indices both during normal growth and during regeneration (42; 70 and 60%, respectively). This peculiarity in the mitotic activity of hepatocytes of mice of different strains was also present 7 days after the beginning of the experiment. The data obtained indicated the genetic determination of the level of proliferative activity of hepatocytes."} {"id": "PMID:1276456", "title": "[Skin regeneration and metabolic level on administration of thyrostimulin].", "content": "A study was made of the effect of thyrostimulating hormone of the adenohypophysis on the metabolism level and the repair process of the covering tissue depending on the topography of the injuries. Under the effect of the mentioned hormone there was an increase in the level of metabolism; thus favourable conditions were created for the accelerated healing of skin wounds. Stimulation of repair process was the most distinct at the early periods of regeneration. The stimulating effect was revealed irrespective of the topography of the injuries, but was more distinct in the animals in which the wounds were inflicted on the lateral surface of the body.", "contents": "[Skin regeneration and metabolic level on administration of thyrostimulin]. A study was made of the effect of thyrostimulating hormone of the adenohypophysis on the metabolism level and the repair process of the covering tissue depending on the topography of the injuries. Under the effect of the mentioned hormone there was an increase in the level of metabolism; thus favourable conditions were created for the accelerated healing of skin wounds. Stimulation of repair process was the most distinct at the early periods of regeneration. The stimulating effect was revealed irrespective of the topography of the injuries, but was more distinct in the animals in which the wounds were inflicted on the lateral surface of the body."} {"id": "PMID:1276457", "title": "[Morphological and histochemical changes in the rabbit aorta during exogenous and endogenous hyperglycemia].", "content": "Alimentary hyperglycemia and insulin deficiency were accompanied in rats by atherosclerotic affection of the aorta whose degree increased in feeding of cholesterol to such animals. The detected morphological and histochemical changes in the wall of the aorta correlated with the biochemical atherogenic shifts in the blood serum of the corresponding animals groups established earlier.", "contents": "[Morphological and histochemical changes in the rabbit aorta during exogenous and endogenous hyperglycemia]. Alimentary hyperglycemia and insulin deficiency were accompanied in rats by atherosclerotic affection of the aorta whose degree increased in feeding of cholesterol to such animals. The detected morphological and histochemical changes in the wall of the aorta correlated with the biochemical atherogenic shifts in the blood serum of the corresponding animals groups established earlier."} {"id": "PMID:1276458", "title": "[Mitoses in hypertrophied smooth muscle tissue of the rat posterior vena cava].", "content": "Injection of colchicin to rats exposed mitotic dividing leukomyocytes in the hypertrophied muscle tissue of the posterior vena cava. Under these conditions mitotic index didn't exceed 1:1000-1:10000. Many of the cells were in the prophase, this being apparently associated with prolonged mitosis in the leiomyocytes of the vein.", "contents": "[Mitoses in hypertrophied smooth muscle tissue of the rat posterior vena cava]. Injection of colchicin to rats exposed mitotic dividing leukomyocytes in the hypertrophied muscle tissue of the posterior vena cava. Under these conditions mitotic index didn't exceed 1:1000-1:10000. Many of the cells were in the prophase, this being apparently associated with prolonged mitosis in the leiomyocytes of the vein."} {"id": "PMID:1276459", "title": "[Enzymatic heterogeneity of the rat myocardium].", "content": "The histoenzymatic method was applied to the study of distribution of the activity of the redox enzymes in the myocardium of the ventricles in rats; distribution of the activity of lactic and malic dehydrogenase and of alpha-glycerophosphate proved to be the most manifest near the apex of the heart and was expressed in the presence of \"spotty\" areas of increased activity against the general homogeneous background of formazan deposits. The activity of mitochondrial upsilon-glycerophoric dehydrogenase was seen in all the portions of the ventricles and was characterized by an uneven distribution in the sarcoplasm with increase in the direction from the interdisc to the nucleus. Unevenness of distribution of the beta-oxybutyric dehydrogenase activity was detected in some of the animals and was pronounced in all the portions of the myocardium. The intensity of the reaction in detection of succinic dehydrogenase, NAD- and NADP-diaphorases varied but insignificantly.", "contents": "[Enzymatic heterogeneity of the rat myocardium]. The histoenzymatic method was applied to the study of distribution of the activity of the redox enzymes in the myocardium of the ventricles in rats; distribution of the activity of lactic and malic dehydrogenase and of alpha-glycerophosphate proved to be the most manifest near the apex of the heart and was expressed in the presence of \"spotty\" areas of increased activity against the general homogeneous background of formazan deposits. The activity of mitochondrial upsilon-glycerophoric dehydrogenase was seen in all the portions of the ventricles and was characterized by an uneven distribution in the sarcoplasm with increase in the direction from the interdisc to the nucleus. Unevenness of distribution of the beta-oxybutyric dehydrogenase activity was detected in some of the animals and was pronounced in all the portions of the myocardium. The intensity of the reaction in detection of succinic dehydrogenase, NAD- and NADP-diaphorases varied but insignificantly."} {"id": "PMID:1276460", "title": "[Ultrastructural changes in the gallbladder mucous membrane during temporary experimental ischemia].", "content": "Temporary ischemia of the gall bladder was induced in rabbits by ligation of the gall bladder artery with silk. Histological examination revealed vascular disorders, such as hyperemia, blood stasis and focal hemorrhages. Electron microscopic studies showed the presence of increased number dark epithelial cells, expansion of intercellular area, loosening of the basal membrane and defects in it with invagination of the epithelial cells into the submucous layer. The most striking changes were discovered after a thrice-repeated 30-minute occlusion of the gall bladder artery. The degree of destructive changes proved to depend on the number of stimulated spasms (occlusions) and not on the duration of ischemia. This gives grounds to believe that multiple circulatory disorders participated in the complicated pathogenesis of cholecystitis.", "contents": "[Ultrastructural changes in the gallbladder mucous membrane during temporary experimental ischemia]. Temporary ischemia of the gall bladder was induced in rabbits by ligation of the gall bladder artery with silk. Histological examination revealed vascular disorders, such as hyperemia, blood stasis and focal hemorrhages. Electron microscopic studies showed the presence of increased number dark epithelial cells, expansion of intercellular area, loosening of the basal membrane and defects in it with invagination of the epithelial cells into the submucous layer. The most striking changes were discovered after a thrice-repeated 30-minute occlusion of the gall bladder artery. The degree of destructive changes proved to depend on the number of stimulated spasms (occlusions) and not on the duration of ischemia. This gives grounds to believe that multiple circulatory disorders participated in the complicated pathogenesis of cholecystitis."} {"id": "PMID:1276461", "title": "[Morphofunctional state of the cholinergic innervation of the rat pancreas during vagotomy].", "content": "Cholinergic innervation of the albino rat pancreas was investigated under normal conditions and after bilateral subdiaphragmatic vagotomy (one, three, seven, twenty one days and two months after the operation). In control animals cholinergic nerve fibers were found in all the organ structures -- both in the vascular and in the gland-duct systems. Vagotomy resulted in a short-term increase in the nerve fibers revealed at the end of the first day, followed by their decrease on the seventh day; but in two months the number of detectable nerve fibers approached the initial level.", "contents": "[Morphofunctional state of the cholinergic innervation of the rat pancreas during vagotomy]. Cholinergic innervation of the albino rat pancreas was investigated under normal conditions and after bilateral subdiaphragmatic vagotomy (one, three, seven, twenty one days and two months after the operation). In control animals cholinergic nerve fibers were found in all the organ structures -- both in the vascular and in the gland-duct systems. Vagotomy resulted in a short-term increase in the nerve fibers revealed at the end of the first day, followed by their decrease on the seventh day; but in two months the number of detectable nerve fibers approached the initial level."} {"id": "PMID:1276462", "title": "[Toxic action of influenza virus on lymphoid-macrophagal reactions in guinea pigs].", "content": "Influenza viruses with different degrees of virulence for the human being produced various reactions of the lymphoid-macrophagal elements in the peritoneal exudate of guinea pigs inoculated intraperitoneally. The higher the virulence of the strain for the human being -- the deeper the inhibition of the lymphoid and macrophagal cells of guinea pigs. Low virulent strains of influenza virus induced a considerable functional activity of macrophages, but were devoid of the lympholytic activity. Because of close corrleation between the virulence of the virus and the cellular content of the exudate the lymphocytic-macrophagal reaction in the animals resistant to influenza virus could serve for determination of the toxic activity of the viruses under study.", "contents": "[Toxic action of influenza virus on lymphoid-macrophagal reactions in guinea pigs]. Influenza viruses with different degrees of virulence for the human being produced various reactions of the lymphoid-macrophagal elements in the peritoneal exudate of guinea pigs inoculated intraperitoneally. The higher the virulence of the strain for the human being -- the deeper the inhibition of the lymphoid and macrophagal cells of guinea pigs. Low virulent strains of influenza virus induced a considerable functional activity of macrophages, but were devoid of the lympholytic activity. Because of close corrleation between the virulence of the virus and the cellular content of the exudate the lymphocytic-macrophagal reaction in the animals resistant to influenza virus could serve for determination of the toxic activity of the viruses under study."} {"id": "PMID:1276463", "title": "[Venous stasis and state of the microcirculatory bed in the synovial membranes].", "content": "Microcirculatory bed of the synovial membranes was investigated in experiments on dogs during venous stasis. Ligation of the femoral vein and circulatory disturbances led to the alteration of the microcirculatory bed of the synovial membranes, to the overfilling of the venules. Capillary walls became thinner and there developed swellings and protrusions. The extent of the vascular wall changes depended on the calibre of the vessels. One month after the ligation of the vein congestive phenomena in the tissue of the joint capsule proved to decline. This indicated development of collateral venous circulation.", "contents": "[Venous stasis and state of the microcirculatory bed in the synovial membranes]. Microcirculatory bed of the synovial membranes was investigated in experiments on dogs during venous stasis. Ligation of the femoral vein and circulatory disturbances led to the alteration of the microcirculatory bed of the synovial membranes, to the overfilling of the venules. Capillary walls became thinner and there developed swellings and protrusions. The extent of the vascular wall changes depended on the calibre of the vessels. One month after the ligation of the vein congestive phenomena in the tissue of the joint capsule proved to decline. This indicated development of collateral venous circulation."} {"id": "PMID:1276464", "title": "[Role of interstitial cells in prostaglandin synthesis in the kidney medulla].", "content": "An electron-microscopic study of the interstitial cells of the medulla of the kidneys was carried out after the administration of the inhibitor of prostaglandine synthesis -- indometacine. Under these conditions the amount of lipid granules in the interstitial cells increased significantly. The authors consider the results of study to be an evident proof of participation of lipid granules in the synthetic function of the interstitial cells as a \"dep\u00f4t\" of a chemical precursor of prostaglandines synthesized by the interstitial cells.", "contents": "[Role of interstitial cells in prostaglandin synthesis in the kidney medulla]. An electron-microscopic study of the interstitial cells of the medulla of the kidneys was carried out after the administration of the inhibitor of prostaglandine synthesis -- indometacine. Under these conditions the amount of lipid granules in the interstitial cells increased significantly. The authors consider the results of study to be an evident proof of participation of lipid granules in the synthetic function of the interstitial cells as a \"dep\u00f4t\" of a chemical precursor of prostaglandines synthesized by the interstitial cells."} {"id": "PMID:1276465", "title": "[Multichannel recording of gastric electric activity from the surface of the human body].", "content": "Technique of synchronous multichannel stomach biopotential recording from the anterior abdominal wall surface was elaborated. Multichannel electrogastrography permitted to record selective electric oscillation of various portions of the stomach from the surface of the anterior abdominal wall. Space-time and correlation tests of the electric activity of different portions of the stomach were carried out in the course of digestion.", "contents": "[Multichannel recording of gastric electric activity from the surface of the human body]. Technique of synchronous multichannel stomach biopotential recording from the anterior abdominal wall surface was elaborated. Multichannel electrogastrography permitted to record selective electric oscillation of various portions of the stomach from the surface of the anterior abdominal wall. Space-time and correlation tests of the electric activity of different portions of the stomach were carried out in the course of digestion."} {"id": "PMID:1276466", "title": "[Cation-exchange method of determining the state of magnesium, calcium and strontium in blood plasma].", "content": "A method of cation metabolism on cationite KY=2X8 in the balanced-salt form was applied to the study of sorption of Mg2+, Ca2+ and Sr2+ ions from physiological solutions and solutions containing blood plasma of dogs and physiological saline in different ratio. Balance constants, which permitted to determine mol fractions (or the content percentage), of \"free\" and \"bound\" ions of the corresponding metals were calculated from the experiments.", "contents": "[Cation-exchange method of determining the state of magnesium, calcium and strontium in blood plasma]. A method of cation metabolism on cationite KY=2X8 in the balanced-salt form was applied to the study of sorption of Mg2+, Ca2+ and Sr2+ ions from physiological solutions and solutions containing blood plasma of dogs and physiological saline in different ratio. Balance constants, which permitted to determine mol fractions (or the content percentage), of \"free\" and \"bound\" ions of the corresponding metals were calculated from the experiments."} {"id": "PMID:1276467", "title": "Increase in circulating stem cells following chemotherapy in man.", "content": "The number of circulating granulocytic stem cells (CFU-C) was determined by the in vitro methylcellulose technique in cancer patients receiving intermittent chemotherapy. In 17 patients studied prior to therapy, the median CFU-C concentration per 2 X 10(5) mononuclear cells plated was six, compared to a posttreatment median of 23 in 21 patients (p less than 0.001). Large numbers of stem cells were obtained by leukopheresis and cryopreserved with a 99.5% median CFU-C recovery. Cyclical changes in the concentration of stem cells with maximum values of 20 times baseline were demonstrated in a patient studied at weekly intervals during multiple courses of treatment. It was estimated that, at peak CFU-C concentrations, a quantity of stem cells equivalent to that present in a bulk bone marrow harvest could be obtained from the peripheral blood by a 17-liter pheresis. These results suggest that it may be practical to obtain an adequate number of stem cells from the peripheral blood to study autologous stem cell infusion as a means of averting myelosuppression in patients receiving intensive chemotherapy.", "contents": "Increase in circulating stem cells following chemotherapy in man. The number of circulating granulocytic stem cells (CFU-C) was determined by the in vitro methylcellulose technique in cancer patients receiving intermittent chemotherapy. In 17 patients studied prior to therapy, the median CFU-C concentration per 2 X 10(5) mononuclear cells plated was six, compared to a posttreatment median of 23 in 21 patients (p less than 0.001). Large numbers of stem cells were obtained by leukopheresis and cryopreserved with a 99.5% median CFU-C recovery. Cyclical changes in the concentration of stem cells with maximum values of 20 times baseline were demonstrated in a patient studied at weekly intervals during multiple courses of treatment. It was estimated that, at peak CFU-C concentrations, a quantity of stem cells equivalent to that present in a bulk bone marrow harvest could be obtained from the peripheral blood by a 17-liter pheresis. These results suggest that it may be practical to obtain an adequate number of stem cells from the peripheral blood to study autologous stem cell infusion as a means of averting myelosuppression in patients receiving intensive chemotherapy."} {"id": "PMID:1276468", "title": "Assessment of erythrocytic and granulocytic colony formation in an in vivo plasma clot diffusion chamber culture system.", "content": "Normal rat bone marrow cells seeded into a plasma clot diffusion chamber culture developed into erythrocytic and granulocytic colonies in vivo. Chambers implanted into the peritoneal cavity of normal hosts showed erythrocytic colony numbers reaching an initial peak on day 2, declining on days 3--5, and increasing in a secondary growth phase on day 7. Day 2 colonies were evenly dispersed; day 7 colonies were grouped into discrete areas of bursts. Granulocytic colony numbers reached a peak on day 4 and gradually declined through day 7. Cells in various stages of differentiation could be detected in both colony types. Colony numbers were proportional to the number of marrow cells seeded into the chamber. Host animals treated with phenylhydrazine induced a marked increase in erythrocytic colony numbers and size and a decrease in granulocytic colony formation. Host animals treated with endotoxin suppressed erythrocytic colonies while increasing granulocytic colony size. This method may prove advantageous for the study of hematopoietic colony formation in a physiologic environment.", "contents": "Assessment of erythrocytic and granulocytic colony formation in an in vivo plasma clot diffusion chamber culture system. Normal rat bone marrow cells seeded into a plasma clot diffusion chamber culture developed into erythrocytic and granulocytic colonies in vivo. Chambers implanted into the peritoneal cavity of normal hosts showed erythrocytic colony numbers reaching an initial peak on day 2, declining on days 3--5, and increasing in a secondary growth phase on day 7. Day 2 colonies were evenly dispersed; day 7 colonies were grouped into discrete areas of bursts. Granulocytic colony numbers reached a peak on day 4 and gradually declined through day 7. Cells in various stages of differentiation could be detected in both colony types. Colony numbers were proportional to the number of marrow cells seeded into the chamber. Host animals treated with phenylhydrazine induced a marked increase in erythrocytic colony numbers and size and a decrease in granulocytic colony formation. Host animals treated with endotoxin suppressed erythrocytic colonies while increasing granulocytic colony size. This method may prove advantageous for the study of hematopoietic colony formation in a physiologic environment."} {"id": "PMID:1276470", "title": "Decreased alpha globine mRNA in nucleated red cell precursors in alpha thalassemia.", "content": "The alpha thalassemias are associated with a decrease in alpha chain synthesis. Hemoglobin H (HbH) disease is a moderately severe form of alpha thalassemia characterized by the production of 5%--20% of HbH, while alpha thalassemia trait is a milder form of alpha thalassemia. In two patients with HbH disease, the ratio of alpha chain synthesis to beta chain synthesis (alpha/beta ratio) was decreased in both bone marrow cells and reticulocytes. When isolated mRNA from bone marrow cells and reticulocytes was translated in a heterologous cell-free system, the alpha/beta ratios were lower than the intact cell ratios. These findings were confirmed by hybridization of the mRNA of both marrow cells and reticulocytes using purified alpha and beta cDNA probes. In the intact cells of two patients with alpha thalassemia trait, the alpha/beta ratios were also decreased and were similar in marrow cells and reticulocytes. Cell-free studies of translatable mRNA also demonstrated decreased alpha/beta ratios, but, unlike the HbH studies, the cell-free alpha/beta ratios were similar to the intact cell ratios. One hybridization study utilizing peripheral blood mRNA had an alpha/beta ratio consistent with the cell-free ratios. These results indicated that, in both HbH disease and alpha thalassemia trait, there was decreased alpha globin mRNA present in both nucleated red cell precursors and reticulocytes. In addition, the data suggested that there may be translational mechanisms that operate in intact HbH cells which attempt to balance globin chain production. In alpha thalassemia trait cells, no such controls appeared to be active and globin chain synthesis was directly proportional to the amount of alpha and beta globin mRNA in the cells.", "contents": "Decreased alpha globine mRNA in nucleated red cell precursors in alpha thalassemia. The alpha thalassemias are associated with a decrease in alpha chain synthesis. Hemoglobin H (HbH) disease is a moderately severe form of alpha thalassemia characterized by the production of 5%--20% of HbH, while alpha thalassemia trait is a milder form of alpha thalassemia. In two patients with HbH disease, the ratio of alpha chain synthesis to beta chain synthesis (alpha/beta ratio) was decreased in both bone marrow cells and reticulocytes. When isolated mRNA from bone marrow cells and reticulocytes was translated in a heterologous cell-free system, the alpha/beta ratios were lower than the intact cell ratios. These findings were confirmed by hybridization of the mRNA of both marrow cells and reticulocytes using purified alpha and beta cDNA probes. In the intact cells of two patients with alpha thalassemia trait, the alpha/beta ratios were also decreased and were similar in marrow cells and reticulocytes. Cell-free studies of translatable mRNA also demonstrated decreased alpha/beta ratios, but, unlike the HbH studies, the cell-free alpha/beta ratios were similar to the intact cell ratios. One hybridization study utilizing peripheral blood mRNA had an alpha/beta ratio consistent with the cell-free ratios. These results indicated that, in both HbH disease and alpha thalassemia trait, there was decreased alpha globin mRNA present in both nucleated red cell precursors and reticulocytes. In addition, the data suggested that there may be translational mechanisms that operate in intact HbH cells which attempt to balance globin chain production. In alpha thalassemia trait cells, no such controls appeared to be active and globin chain synthesis was directly proportional to the amount of alpha and beta globin mRNA in the cells."} {"id": "PMID:1276471", "title": "Decreased life span and membrane damage of carbamylated erythrocytes in vitro.", "content": "Red blood cells exposed to cyanate (CNO) in vitro have a concentration-dependent decreased cell survival time associated with an inhibition of the ability of the cell membrane to synthesize lipids. The t1/2 of rabbit erythrocytes exposed to 30 mM or 50 mM cyanate for 1 hr at 37 degrees C is reduced from the normal 24 days to 15 and 9 days, respectively. The cyanate-induced defect in membrane lipid metabolism is irreversible. Carbamylation of membrane proteins and damage to metabolism are minimized by limiting exposure in vitro to 15 mM cyanate at 4 degrees C for 30 min. Cells carbamylated under these conditions do not have a shortened life span. Levels of globin carbamylation of 0.5 moles CNO/mole hemoglobin, shown to be clinically effective in prolonging the life span of sickle erythrocytes, are obtained under these conditions and reach maximal levels after only 30 min of incubation. Carbamylation of blood in CPD anticoagulant is inferior to either ACD or heparin. The findings indicate that adequate carbamylation of sickle erythrocytes with minimal red cell membrane damage can be achieved without significant modification of the standard plasmapheresis procedure utilized by the working blood bank.", "contents": "Decreased life span and membrane damage of carbamylated erythrocytes in vitro. Red blood cells exposed to cyanate (CNO) in vitro have a concentration-dependent decreased cell survival time associated with an inhibition of the ability of the cell membrane to synthesize lipids. The t1/2 of rabbit erythrocytes exposed to 30 mM or 50 mM cyanate for 1 hr at 37 degrees C is reduced from the normal 24 days to 15 and 9 days, respectively. The cyanate-induced defect in membrane lipid metabolism is irreversible. Carbamylation of membrane proteins and damage to metabolism are minimized by limiting exposure in vitro to 15 mM cyanate at 4 degrees C for 30 min. Cells carbamylated under these conditions do not have a shortened life span. Levels of globin carbamylation of 0.5 moles CNO/mole hemoglobin, shown to be clinically effective in prolonging the life span of sickle erythrocytes, are obtained under these conditions and reach maximal levels after only 30 min of incubation. Carbamylation of blood in CPD anticoagulant is inferior to either ACD or heparin. The findings indicate that adequate carbamylation of sickle erythrocytes with minimal red cell membrane damage can be achieved without significant modification of the standard plasmapheresis procedure utilized by the working blood bank."} {"id": "PMID:1276472", "title": "A family with red cell pyrimidine 5'-nucleotidase deficiency.", "content": "Congenital hemolytic anemia associated with pyrimidine 5'-nucleotidase deficiency is reported in two siblings. Both have had moderate chronic hemolytic anemia, splenomegaly, and jaundice since early infancy. The peripheral blood smear is characterized by striking red cell basophilic stippling. As this feature has been found in all previously reported cases, it should be the clue to the diagnosis.", "contents": "A family with red cell pyrimidine 5'-nucleotidase deficiency. Congenital hemolytic anemia associated with pyrimidine 5'-nucleotidase deficiency is reported in two siblings. Both have had moderate chronic hemolytic anemia, splenomegaly, and jaundice since early infancy. The peripheral blood smear is characterized by striking red cell basophilic stippling. As this feature has been found in all previously reported cases, it should be the clue to the diagnosis."} {"id": "PMID:1276473", "title": "Protein-mediated uptake of vitamin B12 by isolated mitochondria.", "content": "Protein-mediated B12 uptake by isolated rat liver mitochondria has been shown to be enhanced by plasma transcobalamin (TC-II) but not by salivary R binder in vitro. The process is enhanced by calcium and depends on active mitochondrial respiration. Following uptake, cyanocobalamin is converted to adenosyl and methylcobalamins and released from the mitochondria. TC-II appears to be required for both cellular and mitochondrial uptake of vitamin B12.", "contents": "Protein-mediated uptake of vitamin B12 by isolated mitochondria. Protein-mediated B12 uptake by isolated rat liver mitochondria has been shown to be enhanced by plasma transcobalamin (TC-II) but not by salivary R binder in vitro. The process is enhanced by calcium and depends on active mitochondrial respiration. Following uptake, cyanocobalamin is converted to adenosyl and methylcobalamins and released from the mitochondria. TC-II appears to be required for both cellular and mitochondrial uptake of vitamin B12."} {"id": "PMID:1276474", "title": "Complement-mediated granulocyte dysfunction in paroxysmal nocturnal hemoglobinuria.", "content": "In paroxysmal nocturnal hemoglobinuria (PNH), infection, both viral and bacterial, disproportionate to the mild neutropenia seen in many such patients is responsible for significant morbidity. We report impaired granulocyte chemotaxis efficiency which may contribute to the problems induced by bacterial infections. PNH (but not normal) granulocytes, after exposure to very small concentrations of activated serum complement components, migrate poorly, as documented by their inhibited chemotaxis toward bacterial products or activated complement components in Boyden chambers. The granulocytes remain intact, excluding trypan blue, phagocytosing, and killing bacteria, despite this activated complement exposure. It is also suggested that this chemotactic defect may involve only a clone of cells, analogous to the clonal lysis of PNH erythrocytes; those few granulocytes capable of migration after exposure to activated complement contain normal quantities of leukocyte alkaline phosphatase (LAP), in contrast to the LAP deficiency of the overall PNH granulocyte population. Since bacterial infection may initiate or potentiate hemolysis, one of the major symptoms of the disease, these results could explain much of the morbidity of PNH.", "contents": "Complement-mediated granulocyte dysfunction in paroxysmal nocturnal hemoglobinuria. In paroxysmal nocturnal hemoglobinuria (PNH), infection, both viral and bacterial, disproportionate to the mild neutropenia seen in many such patients is responsible for significant morbidity. We report impaired granulocyte chemotaxis efficiency which may contribute to the problems induced by bacterial infections. PNH (but not normal) granulocytes, after exposure to very small concentrations of activated serum complement components, migrate poorly, as documented by their inhibited chemotaxis toward bacterial products or activated complement components in Boyden chambers. The granulocytes remain intact, excluding trypan blue, phagocytosing, and killing bacteria, despite this activated complement exposure. It is also suggested that this chemotactic defect may involve only a clone of cells, analogous to the clonal lysis of PNH erythrocytes; those few granulocytes capable of migration after exposure to activated complement contain normal quantities of leukocyte alkaline phosphatase (LAP), in contrast to the LAP deficiency of the overall PNH granulocyte population. Since bacterial infection may initiate or potentiate hemolysis, one of the major symptoms of the disease, these results could explain much of the morbidity of PNH."} {"id": "PMID:1276475", "title": "Platelet function in the Chediak-Higashi syndrome.", "content": "Platelet function studies were performed on two patients with the Chediak-Higashi syndrome, one of whom had a history of easy bruising unrelated to thrombocytopenia. Both patients had prolonged bleeding times, abnormal platelet aggregation, and a defect of platelet storage granules, manifested by reduced platelet ADP, an increased ATP/ADP ratio, increased adenine nucleotide specific radioactivity after 3H-adenine labeling, and decreased platelet uptake of radioactive 5-hydroxytryptamine. These findings confirm preliminary data in animals with the Chediak-Higashi syndrome, provide and explanation for impaired primary hemostasis in these patients, and illustrate another disorder in which platelet storage-pool deficiency occurs.", "contents": "Platelet function in the Chediak-Higashi syndrome. Platelet function studies were performed on two patients with the Chediak-Higashi syndrome, one of whom had a history of easy bruising unrelated to thrombocytopenia. Both patients had prolonged bleeding times, abnormal platelet aggregation, and a defect of platelet storage granules, manifested by reduced platelet ADP, an increased ATP/ADP ratio, increased adenine nucleotide specific radioactivity after 3H-adenine labeling, and decreased platelet uptake of radioactive 5-hydroxytryptamine. These findings confirm preliminary data in animals with the Chediak-Higashi syndrome, provide and explanation for impaired primary hemostasis in these patients, and illustrate another disorder in which platelet storage-pool deficiency occurs."} {"id": "PMID:1276476", "title": "Defective platelet function following the administration of penicillin compounds.", "content": "Platelet function and blood coagulation were studied in five human volunteers receiving penicillin-G in incremental doses of 1.2--48 million U/day, in six volunteers receiving ampicillin in incremental doses of 60--300 mg/kg/day (4--20 g/day), and in six volunteers receiving methicillin in incremental doses of 60--300 mg/kg/day. Coagulation tests remained normal in all 17 volunteers. However, ADP-induced platelet aggregation became abnormal in every subject except one receiving ampicillin and one receiving methicillin. Defective aggregation occurred with predictability with the following doses: penicillin-G, 24 million U/day; ampicillin, 300 mg/kg/day; methicillin, 300 mg/kg/day. All volunteers given penicillin-G and all given ampicillin experienced dose-related prolongation of bleeding time which did not occur with methicillin. Striking prolongation of bleeding time occurred only with penicillin-G in doses of 48 million U/day. Other tests of platelet function including clot retraction, platelet factor 3 availability, and collagen-induced or epinephrine-induced aggregation remained normal during the administration of these drugs. Measurement of intracellular adenine nucleotides revealed that the ADP and ATP content of platelets was unaffected. It appears that at least one mechanism by which the penicillin compounds alter platelet behavior is by interfering with activation of these cells by ADP.", "contents": "Defective platelet function following the administration of penicillin compounds. Platelet function and blood coagulation were studied in five human volunteers receiving penicillin-G in incremental doses of 1.2--48 million U/day, in six volunteers receiving ampicillin in incremental doses of 60--300 mg/kg/day (4--20 g/day), and in six volunteers receiving methicillin in incremental doses of 60--300 mg/kg/day. Coagulation tests remained normal in all 17 volunteers. However, ADP-induced platelet aggregation became abnormal in every subject except one receiving ampicillin and one receiving methicillin. Defective aggregation occurred with predictability with the following doses: penicillin-G, 24 million U/day; ampicillin, 300 mg/kg/day; methicillin, 300 mg/kg/day. All volunteers given penicillin-G and all given ampicillin experienced dose-related prolongation of bleeding time which did not occur with methicillin. Striking prolongation of bleeding time occurred only with penicillin-G in doses of 48 million U/day. Other tests of platelet function including clot retraction, platelet factor 3 availability, and collagen-induced or epinephrine-induced aggregation remained normal during the administration of these drugs. Measurement of intracellular adenine nucleotides revealed that the ADP and ATP content of platelets was unaffected. It appears that at least one mechanism by which the penicillin compounds alter platelet behavior is by interfering with activation of these cells by ADP."} {"id": "PMID:1276477", "title": "Platelet inhibition by sodium nitroprusside, a smooth muscle inhibitor.", "content": "The effects of sodium nitroprusside (N.P.), a pure smooth muscle inhibitor, on platelet function were studied. Platelet-rich plasmas (PRP) from normal controls and from patients receiving N.P. were studied in vitro for aggregation in response to adenosine diphosphate (ADP), epinephrine, and collagen. Platelet ADP release (release reaction) was also investigated. Normal platelets demonstrated marked inhibition of aggregation when incubated with N.P. for 3 min. Prolonging the incubation was without additional effect. ADP and ATP release from platelets in response to collagen was also inhibited. PRP from patients receiving nitroprusside at concentrations between 25 mug/min an 165 mug/min showed inhibition of aggregation when compared to findings prior to the administration of N.P. N.P. acts by inhibiting contractile proteins and thus platelet ADP release and aggregation may depend on contraction of platelet smooth muscle-like protein, thrombosthenin.", "contents": "Platelet inhibition by sodium nitroprusside, a smooth muscle inhibitor. The effects of sodium nitroprusside (N.P.), a pure smooth muscle inhibitor, on platelet function were studied. Platelet-rich plasmas (PRP) from normal controls and from patients receiving N.P. were studied in vitro for aggregation in response to adenosine diphosphate (ADP), epinephrine, and collagen. Platelet ADP release (release reaction) was also investigated. Normal platelets demonstrated marked inhibition of aggregation when incubated with N.P. for 3 min. Prolonging the incubation was without additional effect. ADP and ATP release from platelets in response to collagen was also inhibited. PRP from patients receiving nitroprusside at concentrations between 25 mug/min an 165 mug/min showed inhibition of aggregation when compared to findings prior to the administration of N.P. N.P. acts by inhibiting contractile proteins and thus platelet ADP release and aggregation may depend on contraction of platelet smooth muscle-like protein, thrombosthenin."} {"id": "PMID:1276478", "title": "Distribution of phospholipids, fatty acids, and platelet factor 3 activity among subcellular fractions of human platelets.", "content": "As compared with other methods, our recently reported method for subcellular fractionation of human platelets improves the separation of mitochondria, alpha granules, and lysosomal enzyme activities. The relative purity of these fractions has led us to undertake the present study to compare the subcellular distribution of phospholipids, fatty acids, and platelet factor 3 (clot-promoting) activity. Two findings pertaining to distribution of phospholipids were entirely new. (1) In the alpha granule zone, plasmalogen phosphatidyl ethanolamine peaked at the expense of diacyl phosphatidyl ethanolamine. (2) The fatty acid composition of the membrane lysophosphatidyl choline suggested that it may have been formed by the action of platelet phospholipase A2 activity. The fatty acids of the membranes showed a markedly asymmetrical distribution in noncholine versus choline phospholipids. The latter held 94%, 72%, and 85%, respectively, of the total content of 16:0, 18:1, and 18:2 fatty acids, whereas 55% of the 18:0, 72% of 20:4, and 67% of higher polyenoic acids other than 20:4 were esterified to the noncholine group. The most important new information related to clot-promoting activity, which, on the basis of protein content, was highest in the membrane fractions, but on the basis of phospholipid content in the nonmembranous fractions. The discussion centers on possible explanations for this novel finding.", "contents": "Distribution of phospholipids, fatty acids, and platelet factor 3 activity among subcellular fractions of human platelets. As compared with other methods, our recently reported method for subcellular fractionation of human platelets improves the separation of mitochondria, alpha granules, and lysosomal enzyme activities. The relative purity of these fractions has led us to undertake the present study to compare the subcellular distribution of phospholipids, fatty acids, and platelet factor 3 (clot-promoting) activity. Two findings pertaining to distribution of phospholipids were entirely new. (1) In the alpha granule zone, plasmalogen phosphatidyl ethanolamine peaked at the expense of diacyl phosphatidyl ethanolamine. (2) The fatty acid composition of the membrane lysophosphatidyl choline suggested that it may have been formed by the action of platelet phospholipase A2 activity. The fatty acids of the membranes showed a markedly asymmetrical distribution in noncholine versus choline phospholipids. The latter held 94%, 72%, and 85%, respectively, of the total content of 16:0, 18:1, and 18:2 fatty acids, whereas 55% of the 18:0, 72% of 20:4, and 67% of higher polyenoic acids other than 20:4 were esterified to the noncholine group. The most important new information related to clot-promoting activity, which, on the basis of protein content, was highest in the membrane fractions, but on the basis of phospholipid content in the nonmembranous fractions. The discussion centers on possible explanations for this novel finding."} {"id": "PMID:1276479", "title": "Antibodies to factor VIII. V. Patterns of immune response to factor VIII in hemophilia A.", "content": "The natural history of factor VIII antibodies was studied in 20 severe, multitransfused hemophiliacs. Two patterns of humoral immune reactivity were observed. In one group of ten, who developed antibodies after an average of 22 cumulative exposure days to factor VIII, the antibody titers increased after each antigenic stimulation or persisted for years in the absence of transfusion. These patients were designated as high-responding hemophiliacs. In the second group of ten patients, the factor VIII neutralizing activity appeared after a longer exposure period (48 days). Antibody titers remained low, and there was no significant difference in individual titers before and 8--20 days following transfusion. Antibody affinity did not increase after renewed antigenic challenge. This pattern characterized low-responding hemophiliacs. The latter group of patients benefited from repeated placement therapy required by the clinical situation.", "contents": "Antibodies to factor VIII. V. Patterns of immune response to factor VIII in hemophilia A. The natural history of factor VIII antibodies was studied in 20 severe, multitransfused hemophiliacs. Two patterns of humoral immune reactivity were observed. In one group of ten, who developed antibodies after an average of 22 cumulative exposure days to factor VIII, the antibody titers increased after each antigenic stimulation or persisted for years in the absence of transfusion. These patients were designated as high-responding hemophiliacs. In the second group of ten patients, the factor VIII neutralizing activity appeared after a longer exposure period (48 days). Antibody titers remained low, and there was no significant difference in individual titers before and 8--20 days following transfusion. Antibody affinity did not increase after renewed antigenic challenge. This pattern characterized low-responding hemophiliacs. The latter group of patients benefited from repeated placement therapy required by the clinical situation."} {"id": "PMID:1276480", "title": "Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII.", "content": "The course and treatment of a life-threatening hemorrhagic episode in a patient with hemophilia A whose plasma contained a high concentration of an inhibitor of factor VIII activity is presented. The inhibitor of factor VIII was localized to the most anodal fractions of immunoglobulin G on electrophoresis, and was thus presumed to be an antibody directed against factor VIII. No therapeutic benefit occurred with infusions of massive amounts of fresh blood and factor VIII concentrates, or with a brief course of immunosuppressive therapy. Administration of standard and activated prothrombin complex concentrates resulted in reduction of the partial thromboplastin time to almost normal values and control of hemorrhage. Eight months later, another hemorrhagic episode occurred. Although a higher titer of inhibitor of factor VIII activity was still present in the patient's plasma, a beneficial therapeutic response was again achieved with standard prothrombin complex infusions.", "contents": "Use of prothrombin complex concentrates in the treatment of a hemophilic patient with an inhibitor of factor VIII. The course and treatment of a life-threatening hemorrhagic episode in a patient with hemophilia A whose plasma contained a high concentration of an inhibitor of factor VIII activity is presented. The inhibitor of factor VIII was localized to the most anodal fractions of immunoglobulin G on electrophoresis, and was thus presumed to be an antibody directed against factor VIII. No therapeutic benefit occurred with infusions of massive amounts of fresh blood and factor VIII concentrates, or with a brief course of immunosuppressive therapy. Administration of standard and activated prothrombin complex concentrates resulted in reduction of the partial thromboplastin time to almost normal values and control of hemorrhage. Eight months later, another hemorrhagic episode occurred. Although a higher titer of inhibitor of factor VIII activity was still present in the patient's plasma, a beneficial therapeutic response was again achieved with standard prothrombin complex infusions."} {"id": "PMID:1276481", "title": "Combined deficiency of factor V and factor VIII. A report of another case.", "content": "A patient with combined factor V and factor VIII deficiency is presented. The bleeding manifestations were: easy bruising, post-traumatic bleeding, bleeding after tooth extractions. The main laboratory feature was a prolonged partial thromboplastin time which was corrected by the addition of adsorbed normal plasma but not by the addition of normal serum, hemophilia A plasma of another patient with combined factor V and factor VIII deficiency. The thromboplastin generation test was clearly abnormal and was corrected by the addition of adsorbed normal plasma but not by addition of normal serum. Prothrombin consumption was also defective. Prothrombin time was slightly prolonged too, Thrombin time, platelet and vascular tests were within normal limits and there was no hyperfibrinolysis. Factor VIII was 8% of normal, whereas factor V was 14% of normal. Factor VIII associated antigen was normal. All other clotting factors were within normal limits. The parents of the propositus were consanguineous (first cousins) but had normal factor V and factor VIII activity and normal factor VIII antigen. The same was true for other family members. The hereditary transmission of the condition appears autosomal recessive.", "contents": "Combined deficiency of factor V and factor VIII. A report of another case. A patient with combined factor V and factor VIII deficiency is presented. The bleeding manifestations were: easy bruising, post-traumatic bleeding, bleeding after tooth extractions. The main laboratory feature was a prolonged partial thromboplastin time which was corrected by the addition of adsorbed normal plasma but not by the addition of normal serum, hemophilia A plasma of another patient with combined factor V and factor VIII deficiency. The thromboplastin generation test was clearly abnormal and was corrected by the addition of adsorbed normal plasma but not by addition of normal serum. Prothrombin consumption was also defective. Prothrombin time was slightly prolonged too, Thrombin time, platelet and vascular tests were within normal limits and there was no hyperfibrinolysis. Factor VIII was 8% of normal, whereas factor V was 14% of normal. Factor VIII associated antigen was normal. All other clotting factors were within normal limits. The parents of the propositus were consanguineous (first cousins) but had normal factor V and factor VIII activity and normal factor VIII antigen. The same was true for other family members. The hereditary transmission of the condition appears autosomal recessive."} {"id": "PMID:1276482", "title": "[Malformations, anomalies and variations in patients with severe iron deficiency].", "content": "In severe iron deficiency which frequently occurs in the population of Turkey, malformations, anomalies and variations are often observed. In 190 patients with severe iron deficiency of long duration such abnormalities could be found in 107 cases. The abnormal changes were of different character and occured in various parts of the body. In the majority multiple changes, ranging from 2 to 7 and more could be registered. 100 persons showing no iron deficiency and no anemia presented a much lower incidence of the same changes; in a second group of 54 patients suffering from a severe anemia without iron deficiency the incidence was still lower. These observations suggest that the occurrence of the abnormalities is closely connected with the iron deficiency. The character of the abnormal changes which are not susceptible to iron treatment are pointing to a prenatal origin. The diversity of the changes, the occurrence in various parts of the body and skeleton as well as the multiplicity of incidence are showing that they are due to impairment of the process of development in the embryonic organism. This view is supported by the results of the examination of the chromosomes. A distinct relation could be established between the incidence of the malformations and the occurrence of the chromosomal aberrations. As the iron deficiency in the Turkish population is mainly caused by an insufficient supply of iron with the food it is likely that by sufficient iron supply in pregnant women the incidence of malformations and anomalies caused by the iron deficiency can be prevented and by a general amelioration of the nutrition their occurrence in the population markedly reduced.", "contents": "[Malformations, anomalies and variations in patients with severe iron deficiency]. In severe iron deficiency which frequently occurs in the population of Turkey, malformations, anomalies and variations are often observed. In 190 patients with severe iron deficiency of long duration such abnormalities could be found in 107 cases. The abnormal changes were of different character and occured in various parts of the body. In the majority multiple changes, ranging from 2 to 7 and more could be registered. 100 persons showing no iron deficiency and no anemia presented a much lower incidence of the same changes; in a second group of 54 patients suffering from a severe anemia without iron deficiency the incidence was still lower. These observations suggest that the occurrence of the abnormalities is closely connected with the iron deficiency. The character of the abnormal changes which are not susceptible to iron treatment are pointing to a prenatal origin. The diversity of the changes, the occurrence in various parts of the body and skeleton as well as the multiplicity of incidence are showing that they are due to impairment of the process of development in the embryonic organism. This view is supported by the results of the examination of the chromosomes. A distinct relation could be established between the incidence of the malformations and the occurrence of the chromosomal aberrations. As the iron deficiency in the Turkish population is mainly caused by an insufficient supply of iron with the food it is likely that by sufficient iron supply in pregnant women the incidence of malformations and anomalies caused by the iron deficiency can be prevented and by a general amelioration of the nutrition their occurrence in the population markedly reduced."} {"id": "PMID:1276483", "title": "Haematological values for the Finnish reindeer.", "content": "Red blood cell counts, haemoglobin, packed cell volumes and total and differential leucocyte counts as well as E-MCHC, E-MCH, E-MCV values and the osmotic fragility of erythrocytes are described for the Finnish reindeer. The samples were taken in early autumn from 52 reindeer of varying ages.", "contents": "Haematological values for the Finnish reindeer. Red blood cell counts, haemoglobin, packed cell volumes and total and differential leucocyte counts as well as E-MCHC, E-MCH, E-MCV values and the osmotic fragility of erythrocytes are described for the Finnish reindeer. The samples were taken in early autumn from 52 reindeer of varying ages."} {"id": "PMID:1276484", "title": "[Biologic activity of various intrinsic factor preparations in Schilling's test].", "content": "In 16 patients with pernicious anaemia investigations concerning the biological activity of 7 different Intrinsic-factor praeparations by means of the urinary excretion test were performed. Oral longterm-pretreatment with IF and biologically inactive IF-praeparations may cause false pathologic results.", "contents": "[Biologic activity of various intrinsic factor preparations in Schilling's test]. In 16 patients with pernicious anaemia investigations concerning the biological activity of 7 different Intrinsic-factor praeparations by means of the urinary excretion test were performed. Oral longterm-pretreatment with IF and biologically inactive IF-praeparations may cause false pathologic results."} {"id": "PMID:1276485", "title": "[Experimental studies on population genetics of complement 3 (C3) and serum component transferin (Tf) in the population of Northern Bavaria].", "content": "Within a population sample concerning 2500 blood donors of Northern Bavaria, the population genetics of the Systems C3 and Tf have been investigated. The calculated gene frequencies are: C3S = 0,789; C3F = 0,2028; C3Var. = 0,0082; TfC = 0,9960; TfVar. = 0,0040. As a \"new\" variant C3F1,55 has been found.", "contents": "[Experimental studies on population genetics of complement 3 (C3) and serum component transferin (Tf) in the population of Northern Bavaria]. Within a population sample concerning 2500 blood donors of Northern Bavaria, the population genetics of the Systems C3 and Tf have been investigated. The calculated gene frequencies are: C3S = 0,789; C3F = 0,2028; C3Var. = 0,0082; TfC = 0,9960; TfVar. = 0,0040. As a \"new\" variant C3F1,55 has been found."} {"id": "PMID:1276491", "title": "A study of the inhalation of pentachlorophenol by rats. Part I. A method for the determination of pentachlorophenol in rat plasma, urine and tissue and in aerosol samples.", "content": "Simple and flexible methods have been designed for the determination of pentachlorophenol in animal tissue, blood plasma, urine, and aerosol. The isolation of the pesticide is achieved through its extraction with benzene or hexane after acidification, derivatization, and its subsequent purification through florosil columns. A brief describption of the sampling methods is included. The described procedures are especially suited for exposure experiments where different types of samples with a large variety of PCP concentrations are encountered.", "contents": "A study of the inhalation of pentachlorophenol by rats. Part I. A method for the determination of pentachlorophenol in rat plasma, urine and tissue and in aerosol samples. Simple and flexible methods have been designed for the determination of pentachlorophenol in animal tissue, blood plasma, urine, and aerosol. The isolation of the pesticide is achieved through its extraction with benzene or hexane after acidification, derivatization, and its subsequent purification through florosil columns. A brief describption of the sampling methods is included. The described procedures are especially suited for exposure experiments where different types of samples with a large variety of PCP concentrations are encountered."} {"id": "PMID:1276492", "title": "A study of the inhalation of pentachlorophenol by rats. Part II. A new inhalation exposure system for high doses in short exposure time.", "content": "An exposure system has been designed which is applicable for short time, acute exposures of rats to the aerosol of pesticides. The aerosol is generated by compressed air aspiration. Larger droplets are removed by a cyclone separation. The exposure chamber has 12 inhalation sites separated from the animal containers by rubber seals which insure inhalation as the only route of exposure.", "contents": "A study of the inhalation of pentachlorophenol by rats. Part II. A new inhalation exposure system for high doses in short exposure time. An exposure system has been designed which is applicable for short time, acute exposures of rats to the aerosol of pesticides. The aerosol is generated by compressed air aspiration. Larger droplets are removed by a cyclone separation. The exposure chamber has 12 inhalation sites separated from the animal containers by rubber seals which insure inhalation as the only route of exposure."} {"id": "PMID:1276511", "title": "New library buildings. Part VI: Sciences Library, Brown University.", "content": "Brown was one of the first universities in the nation to combine its science collections into a single library in the interest of aiding interdisciplinary teaching and research. This paper discusses the evolution of the Sciences Library and its resources, the development of the medical education program, and the physical aspects of the new library building. A fifteen-story tower, housing the collections of the physical, biological, and medical sciences, symbolizes the interdisciplinary approach to teaching and research at Brown University.", "contents": "New library buildings. Part VI: Sciences Library, Brown University. Brown was one of the first universities in the nation to combine its science collections into a single library in the interest of aiding interdisciplinary teaching and research. This paper discusses the evolution of the Sciences Library and its resources, the development of the medical education program, and the physical aspects of the new library building. A fifteen-story tower, housing the collections of the physical, biological, and medical sciences, symbolizes the interdisciplinary approach to teaching and research at Brown University."} {"id": "PMID:1276512", "title": "The art of planning for library personnel.", "content": "A review of the planning process for personnel at the University of Cincinnati's new Health Sciences Library is discussed. The staff of two libraries were involved in the plan. The final organizational pattern encompassed present staff plus justification for additional staff who would be necessary in the expanded facility.", "contents": "The art of planning for library personnel. A review of the planning process for personnel at the University of Cincinnati's new Health Sciences Library is discussed. The staff of two libraries were involved in the plan. The final organizational pattern encompassed present staff plus justification for additional staff who would be necessary in the expanded facility."} {"id": "PMID:1276513", "title": "The PHILSOM system--one user's experience.", "content": "The University of Texas Health Science Center at San Antonio joined the PHILSOM system, a comprehensive serials control network, in 1971. The experiences of the library in using the system are described. The major benefit of the system has been multiple copies of the holdings list which have made the serial records publicly accessible and significantly increased their value. Tallies of these lists' use indicate that more than half of serials-related questions are now answered directly by the users. The effects of PHILSOM on the procedures of the serials department--processing, claiming, bindery, and personnel are described. Costs to the network and the UTHSCSA Library are briefly summarized.", "contents": "The PHILSOM system--one user's experience. The University of Texas Health Science Center at San Antonio joined the PHILSOM system, a comprehensive serials control network, in 1971. The experiences of the library in using the system are described. The major benefit of the system has been multiple copies of the holdings list which have made the serial records publicly accessible and significantly increased their value. Tallies of these lists' use indicate that more than half of serials-related questions are now answered directly by the users. The effects of PHILSOM on the procedures of the serials department--processing, claiming, bindery, and personnel are described. Costs to the network and the UTHSCSA Library are briefly summarized."} {"id": "PMID:1276521", "title": "Secondary repair of bilateral cleft lip deformities. A two-stage approach.", "content": "A two-stage procedure using previously described principles has been designed to achieve muscle-to-muscle union, narrowing of the philtrum and lengthening of the columella. In addition fistulas may be corrected simultaneously.", "contents": "Secondary repair of bilateral cleft lip deformities. A two-stage approach. A two-stage procedure using previously described principles has been designed to achieve muscle-to-muscle union, narrowing of the philtrum and lengthening of the columella. In addition fistulas may be corrected simultaneously."} {"id": "PMID:1276524", "title": "Reduction of very large breasts: the inferior flap technique of Robertson.", "content": "The Robertson technique of reducing very large breast is decribed. In 24 patients it has proved to be a simple, reliable, reproducible procedure without complications, which provides well-shaped breasts of a normal size.", "contents": "Reduction of very large breasts: the inferior flap technique of Robertson. The Robertson technique of reducing very large breast is decribed. In 24 patients it has proved to be a simple, reliable, reproducible procedure without complications, which provides well-shaped breasts of a normal size."} {"id": "PMID:1276525", "title": "The size of the human omentum and methods of lengthening it for transplantation.", "content": "The size of the omentum is variable and can only be predicted within the standard deviations. However, the lower limits of its size have now been ascertained over a large series and it is clear that it could be lengthened sufficiently to reach the vault of skull, mid-leg or mid-forearm levels in all cases. Of course, to do so will decrease its width. An alternative to pedicle transfer is to use the whole omentum as a free transplant by vascular anastomosis.", "contents": "The size of the human omentum and methods of lengthening it for transplantation. The size of the omentum is variable and can only be predicted within the standard deviations. However, the lower limits of its size have now been ascertained over a large series and it is clear that it could be lengthened sufficiently to reach the vault of skull, mid-leg or mid-forearm levels in all cases. Of course, to do so will decrease its width. An alternative to pedicle transfer is to use the whole omentum as a free transplant by vascular anastomosis."} {"id": "PMID:1276528", "title": "A traumatic fistula of the submandibular gland.", "content": "A salivary fistula of a submandibular gland was successfully treated by excision of that gland.", "contents": "A traumatic fistula of the submandibular gland. A salivary fistula of a submandibular gland was successfully treated by excision of that gland."} {"id": "PMID:1276529", "title": "Tryptophan metabolism in the isolated perfused liver of the rat: effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation.", "content": "1 The effect of tryptophan concentration on the rate of kynurenine appearance and tryptophan disappearance in the medium perfused through the isolated liver of the rat has been investigated. The effect of pretreatment of the rat with hydrocortisone or allopurinol was also examined, together with the effects of these treatments on liver tryptophan pyrrolase activity measured in vitro at the beginning and end of perfusion. 2 Hydrocortisone (5 mg/kg) injection 3 h before perfusion resulted in a four-fold increase in kynurenine production by the liver during perfusion with a medium containing either 0.1 mmol/1 or 1.0 mmol/1 tryptophan. Injection of allopurinol (20 mg/kg) together with hydrocortisone and addition of allopurinol (4 mg/100 ml) to the medium abolished the hydrocortisone-induced rise of kynurenine in the 0.1 mmol/tryptophan medium but not the 1.0 mmol/1 tryptophan medium. 3 Injection of cycloheximide (30 mg/kg) with hydrocortisone (5 mg/kg) 3 h before perfusion inhibited the hydrocortisone-induced rise of kynurenine production and the increase in pyrrolase activity measured in vitro both before and at the end of perfusion with 1.0 mmol/1 tryptophan. This last result suggests that protein synthesis is involved not only in hydrocortisone induction of pyrrolase but also in substrate induction. 4 Kynurenine production in the 1.0 mmol/1 tryptophan medium was less in both saline- and hydrocortisone-treated older rats (335-450 g) compared to younger rats (180-220 g). In agreement with a previous study, pyrrolase activity in vitro was also lower in both saline- and hydrocortisone- treated older rats at the beginning of the perfusion although activity had risen equally in both young and older rats at the end of perfusion. 5 There was little correlation between the rate of tryptophan disappearance from the medium and the activity of tryptophan pyrrolase either as measured in vitro or as indicated by the rate of kynurenine production. 6 In general, the production of kynurenine in the medium at the end of the 60 min perfusion was indicative of in vitro pyrrolase activity at the start of the perfusion. 7 It is concluded that while in vitro pyrrolase assay does not give a quantitative index of kynurenne production, it does provide a qualitative index. Furthermore, if kynurenine production in the isolated perfused liver of the rat is indicative of in vivo pyrrolase activity, then hydrocortisone must induce pyrrolase activity in vivo.", "contents": "Tryptophan metabolism in the isolated perfused liver of the rat: effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation. 1 The effect of tryptophan concentration on the rate of kynurenine appearance and tryptophan disappearance in the medium perfused through the isolated liver of the rat has been investigated. The effect of pretreatment of the rat with hydrocortisone or allopurinol was also examined, together with the effects of these treatments on liver tryptophan pyrrolase activity measured in vitro at the beginning and end of perfusion. 2 Hydrocortisone (5 mg/kg) injection 3 h before perfusion resulted in a four-fold increase in kynurenine production by the liver during perfusion with a medium containing either 0.1 mmol/1 or 1.0 mmol/1 tryptophan. Injection of allopurinol (20 mg/kg) together with hydrocortisone and addition of allopurinol (4 mg/100 ml) to the medium abolished the hydrocortisone-induced rise of kynurenine in the 0.1 mmol/tryptophan medium but not the 1.0 mmol/1 tryptophan medium. 3 Injection of cycloheximide (30 mg/kg) with hydrocortisone (5 mg/kg) 3 h before perfusion inhibited the hydrocortisone-induced rise of kynurenine production and the increase in pyrrolase activity measured in vitro both before and at the end of perfusion with 1.0 mmol/1 tryptophan. This last result suggests that protein synthesis is involved not only in hydrocortisone induction of pyrrolase but also in substrate induction. 4 Kynurenine production in the 1.0 mmol/1 tryptophan medium was less in both saline- and hydrocortisone-treated older rats (335-450 g) compared to younger rats (180-220 g). In agreement with a previous study, pyrrolase activity in vitro was also lower in both saline- and hydrocortisone- treated older rats at the beginning of the perfusion although activity had risen equally in both young and older rats at the end of perfusion. 5 There was little correlation between the rate of tryptophan disappearance from the medium and the activity of tryptophan pyrrolase either as measured in vitro or as indicated by the rate of kynurenine production. 6 In general, the production of kynurenine in the medium at the end of the 60 min perfusion was indicative of in vitro pyrrolase activity at the start of the perfusion. 7 It is concluded that while in vitro pyrrolase assay does not give a quantitative index of kynurenne production, it does provide a qualitative index. Furthermore, if kynurenine production in the isolated perfused liver of the rat is indicative of in vivo pyrrolase activity, then hydrocortisone must induce pyrrolase activity in vivo."} {"id": "PMID:1276530", "title": "Mechanism of the indirect sympathomimetic effect of 5-hydroxytrypt-amine on the isolated heart of the rabbit.", "content": "1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP). 2 The cardiac stimulant effects of 5-HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist. 3 Responses to 5-HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6-hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated. 4 Rapid, reversible and selective tachyphylaxis to 5-HT was demonstrated during perfusion with 5-HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5-HT were also reduced. 5 Perfusion of hearts with colchicine inhibited stimulant responses to 5-HT and DMPP but had little effect on responses to noradrenaline or tyramine. 6 Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5-HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine. 7 Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5-HT and DMPP unaffected. 8 5-HT, tyramine and DMPP evoked 3H-release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3H]-(-)-noradrenaline. The pattern of release evoked by 5-HT was similar to that of DMPP but differed from that of tyramine. 9 Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/1 did not affect 3H-overflow after tyramine but greatly inhibited that evoked by 5-HT and DMPP. 10 The results confirm that the stimulatn effects of 5-HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium-dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement).", "contents": "Mechanism of the indirect sympathomimetic effect of 5-hydroxytrypt-amine on the isolated heart of the rabbit. 1 Rabbit isolated hearts, perfused by the Langendorff technique, were used to investigate the indirect sympathomimetic effects of 5-hydroxytryptamine (5-HT). Comparisons were made with noradrenaline and with two indirectly acting sympathomimetic agents with entirely different mechanisms of action, tyramine and dimethylphenylpiperazinium (DMPP). 2 The cardiac stimulant effects of 5-HT, tyramine and DMPP were inhibited by propranolol and practolol and the pA2 values obtained were similar to those obtained with noradrenaline as the agonist. 3 Responses to 5-HT, tyramine and DMPP were greatly reduced on hearts from rabbits pretreated with 6-hydroxydopamine. Such hearts had less than 7% of their normal catecholamine concentration and no fluorescence characteristic of noradrenaline in the cardiac sympathetic nerves could be demonstrated. 4 Rapid, reversible and selective tachyphylaxis to 5-HT was demonstrated during perfusion with 5-HT. In hearts desensitized to DMPP by perfusion with DMPP, responses to 5-HT were also reduced. 5 Perfusion of hearts with colchicine inhibited stimulant responses to 5-HT and DMPP but had little effect on responses to noradrenaline or tyramine. 6 Desmethylimipramine enhanced cardiac stimulant responses to noradrenaline and to a lesser extent, those to 5-HT and DMPP. Responses to tyramine were consistently inhibited by desmethylimipramine. 7 Tetrodotoxin abolished responses of the heart to electrical nerve stimulation but left responses to noradrenaline, 5-HT and DMPP unaffected. 8 5-HT, tyramine and DMPP evoked 3H-release from hearts whose neuronal noradrenaline stores had been labelled by perfusion with [3H]-(-)-noradrenaline. The pattern of release evoked by 5-HT was similar to that of DMPP but differed from that of tyramine. 9 Reducing the calcium concentration in the Tyrode solution from 3.6 to 0.2 mEq/1 did not affect 3H-overflow after tyramine but greatly inhibited that evoked by 5-HT and DMPP. 10 The results confirm that the stimulatn effects of 5-HT on the rabbit isolated heart are the result of noradrenaline release. They further suggest that the site of the release is the terminal sympathetic nerve network. The mechanism of release shows more similarities to that of DMPP (calcium-dependent depolarization and exocytosis) than to that of tyramine (neuronal uptake and stoichiometric displacement)."} {"id": "PMID:1276531", "title": "The different effects of D-600 (methoxyverapamil) on the release of adrenal catecholamines induced by acetylcholine, high potassium or sodium deprivation.", "content": "1 Bovine adrenal glands were perfused with Locke solution and catecholamine release was induced by acetylcholine, by a depolarizing concentration of potassium, or by omission of sodium from the perfusion fluid. 2 D-600 (methoxyverapamil) at the concentration of 30 muM produced a 23% inhibition of catecholamine release evoked by acetylcholine (0.1 mM) in the presence of physostigmine (10 muM). 3 A concentration of D-600 of 0.3 mM produced 86% and 85% inhibition in the output of catecholamines in response to acetylcholine and high potassium respectively. 4 D-600 (0.3 mM) failed to block the release of catecholamines evoked by sodium deprivation. 5 The results suggest the involvement of intracellular calcium in the exocytotic release of catecholamines induced by sodium omission.", "contents": "The different effects of D-600 (methoxyverapamil) on the release of adrenal catecholamines induced by acetylcholine, high potassium or sodium deprivation. 1 Bovine adrenal glands were perfused with Locke solution and catecholamine release was induced by acetylcholine, by a depolarizing concentration of potassium, or by omission of sodium from the perfusion fluid. 2 D-600 (methoxyverapamil) at the concentration of 30 muM produced a 23% inhibition of catecholamine release evoked by acetylcholine (0.1 mM) in the presence of physostigmine (10 muM). 3 A concentration of D-600 of 0.3 mM produced 86% and 85% inhibition in the output of catecholamines in response to acetylcholine and high potassium respectively. 4 D-600 (0.3 mM) failed to block the release of catecholamines evoked by sodium deprivation. 5 The results suggest the involvement of intracellular calcium in the exocytotic release of catecholamines induced by sodium omission."} {"id": "PMID:1276532", "title": "On the actions of compounds related to dopamine at a neurosecretory synapse.", "content": "1 The effects of a number of substances related to dopamine, including all its methylated derivatives, were investigated on the membrane potential and response to nerve stimulation of cockroach salivary gland cells. 2 Only N-methyldopamine (epinine), N,N-dimethyldopamine and N,N-dimethylnoradrenaline, all with unsubstituted hydroxyl groups, directly resembled dopamine in producing a hyperpolarization which could be as large as that caused by maximal nerve stimulation. During the continued presence of these substances the hyperpolarization waned and responses to nerve stimulation declined. 3 Many of the compounds caused one or both of two other effects, namely an increase in the rate of 'spontaneous miniature hyperpolarizations' and an enhancement of the submaximal responses to single nerve stimuli. There were no obvious structural requirements for these effects.", "contents": "On the actions of compounds related to dopamine at a neurosecretory synapse. 1 The effects of a number of substances related to dopamine, including all its methylated derivatives, were investigated on the membrane potential and response to nerve stimulation of cockroach salivary gland cells. 2 Only N-methyldopamine (epinine), N,N-dimethyldopamine and N,N-dimethylnoradrenaline, all with unsubstituted hydroxyl groups, directly resembled dopamine in producing a hyperpolarization which could be as large as that caused by maximal nerve stimulation. During the continued presence of these substances the hyperpolarization waned and responses to nerve stimulation declined. 3 Many of the compounds caused one or both of two other effects, namely an increase in the rate of 'spontaneous miniature hyperpolarizations' and an enhancement of the submaximal responses to single nerve stimuli. There were no obvious structural requirements for these effects."} {"id": "PMID:1276533", "title": "Evidence concerning the involvement of 5-hydroxytryptamine in the locomotor activity produced by amphetamine or tranylcypromine plus L-DOPA.", "content": "1 Pretreatment of rats with p-chlorophenylalanine (PCPA; 2 X 200 mg/kg) decreased the concentration of 5-hydroxytryptamine (5-HT) in the brain. It also decreased the locomotor activity produced by tranylcypromine plus L-DOPA administration 24 h after the second dose of PCPA. 2 Pretreatment with p-chloroamphetamine, which produced a similar decrease in brain 5-HT concentrations did not decrease the locomotor response to tranylcypromine and L-DOPA. 3 PCPA pretreatment decreased the rise in the concentration of DOPA and dopamine in the brain following tranylcypromine and L-DOPA, suggesting its effect on the dopamine-induced locomotor activity was the result of this drug diminishing dopamine formation in the brain, probably by inhibiting L-DOPA uptake. 4 The locomotor activity produced by tranylcypromine and L-DOPA was not decreased by pretreatment 6 h earlier with disulfiram (400 mg/kg). This argues against the locomotor activity being due to noradrenergic stimulation. 5 PCPA pretreatment did not alter amphetamine-induced stereotypy or the circling behaviour in unilateral nigro-striatal lesioned rats.", "contents": "Evidence concerning the involvement of 5-hydroxytryptamine in the locomotor activity produced by amphetamine or tranylcypromine plus L-DOPA. 1 Pretreatment of rats with p-chlorophenylalanine (PCPA; 2 X 200 mg/kg) decreased the concentration of 5-hydroxytryptamine (5-HT) in the brain. It also decreased the locomotor activity produced by tranylcypromine plus L-DOPA administration 24 h after the second dose of PCPA. 2 Pretreatment with p-chloroamphetamine, which produced a similar decrease in brain 5-HT concentrations did not decrease the locomotor response to tranylcypromine and L-DOPA. 3 PCPA pretreatment decreased the rise in the concentration of DOPA and dopamine in the brain following tranylcypromine and L-DOPA, suggesting its effect on the dopamine-induced locomotor activity was the result of this drug diminishing dopamine formation in the brain, probably by inhibiting L-DOPA uptake. 4 The locomotor activity produced by tranylcypromine and L-DOPA was not decreased by pretreatment 6 h earlier with disulfiram (400 mg/kg). This argues against the locomotor activity being due to noradrenergic stimulation. 5 PCPA pretreatment did not alter amphetamine-induced stereotypy or the circling behaviour in unilateral nigro-striatal lesioned rats."} {"id": "PMID:1276534", "title": "The effect of aspirin on 5-hydroxytryptamine uptake and release by human platelets.", "content": "The influence of aspirin on 5-hydroxytryptamine (5-HT) uptake and storage by human blood platelets has been investigated. Uptake of 5-HT was strongly inhibited. In 30 min aspirin released 50% of the 5-HT that had been incorporated into the platelets prior to the addition of the aspirin. These results are discussed in terms of possible interference with a 5-HT membrane receptor and the impairment of 5-HT storage in the dense granules.", "contents": "The effect of aspirin on 5-hydroxytryptamine uptake and release by human platelets. The influence of aspirin on 5-hydroxytryptamine (5-HT) uptake and storage by human blood platelets has been investigated. Uptake of 5-HT was strongly inhibited. In 30 min aspirin released 50% of the 5-HT that had been incorporated into the platelets prior to the addition of the aspirin. These results are discussed in terms of possible interference with a 5-HT membrane receptor and the impairment of 5-HT storage in the dense granules."} {"id": "PMID:1276535", "title": "Potentiation by desipramine of neuronal responses to mescaline.", "content": "The effect of desipramine on responses of single cortical neurones to mescaline was studied by the microelectrophoretic technique. Both potentiation and antagonism of responses to mescaline by desipramine were observed. The antagonism may be related to the alpha-adrenolytic action of desipramine. The potentiation is unlikely to reflect the uptake blocking action of desipramine, since desipramine does not block the uptake of mescaline in the cerebral cortex. It is suggested that the potentiation may be due to a post-synaptic action of desipramine.", "contents": "Potentiation by desipramine of neuronal responses to mescaline. The effect of desipramine on responses of single cortical neurones to mescaline was studied by the microelectrophoretic technique. Both potentiation and antagonism of responses to mescaline by desipramine were observed. The antagonism may be related to the alpha-adrenolytic action of desipramine. The potentiation is unlikely to reflect the uptake blocking action of desipramine, since desipramine does not block the uptake of mescaline in the cerebral cortex. It is suggested that the potentiation may be due to a post-synaptic action of desipramine."} {"id": "PMID:1276536", "title": "Calcitonin: antagonism at intestinal muscarinic receptors.", "content": "The action of calcitonin was studied on the motility of isolated innervated segments of rabbit and guinea-pig intestines as well as longitudinal muscle with adherent myenteric plexus dissected from the guinea-pig ileum. Calcitonin (0.25 muM) antagonized contractile responses to acetylcholine and the cholinergic response to electrical field stimulation. This hormonal effect was relatively specific since it was not observed at nicotinic receptors or adrenoceptors, nor did calcitonin act as a local anaesthetic or directly on the contractile machinery of smooth muscle. Perivascular adrenergic and intrinsic non-adrenergic inhibitory responses also were unaffected by calcitonin. However, calcitonin did have antihistaminic properties directed against H1-receptors. The concentration of calcitonin required to achieve muscarinic antagonism in our experiments is not reached at the resting level of circulating hormone.", "contents": "Calcitonin: antagonism at intestinal muscarinic receptors. The action of calcitonin was studied on the motility of isolated innervated segments of rabbit and guinea-pig intestines as well as longitudinal muscle with adherent myenteric plexus dissected from the guinea-pig ileum. Calcitonin (0.25 muM) antagonized contractile responses to acetylcholine and the cholinergic response to electrical field stimulation. This hormonal effect was relatively specific since it was not observed at nicotinic receptors or adrenoceptors, nor did calcitonin act as a local anaesthetic or directly on the contractile machinery of smooth muscle. Perivascular adrenergic and intrinsic non-adrenergic inhibitory responses also were unaffected by calcitonin. However, calcitonin did have antihistaminic properties directed against H1-receptors. The concentration of calcitonin required to achieve muscarinic antagonism in our experiments is not reached at the resting level of circulating hormone."} {"id": "PMID:1276537", "title": "Effects of sympathomimetic amines on 45Ca efflux from liver slices.", "content": "The efflux of 45Ca from slices of guinea-pig and rabbit liver is greatly increased by alpha-adrenoceptor agonists. Isoprenaline is much less effective. The effects of these agents on the efflux of 45Ca mirror their actions on 42K loss and suggest that the two may be related. Glucose release from both rabbit and guinea-pig liver slices is increased to a similar extent by either alpha- or beta-receptor agonists. The possible relationship between Ca and K movements and the production of glucose is discussed.", "contents": "Effects of sympathomimetic amines on 45Ca efflux from liver slices. The efflux of 45Ca from slices of guinea-pig and rabbit liver is greatly increased by alpha-adrenoceptor agonists. Isoprenaline is much less effective. The effects of these agents on the efflux of 45Ca mirror their actions on 42K loss and suggest that the two may be related. Glucose release from both rabbit and guinea-pig liver slices is increased to a similar extent by either alpha- or beta-receptor agonists. The possible relationship between Ca and K movements and the production of glucose is discussed."} {"id": "PMID:1276538", "title": "The relationship between cardiotoxicity and plasma digoxin concentration in conscious dogs.", "content": "1 The tendency of a given oral dose of digoxin to induce cardiac dysrhythmia was determined indirectly at various times after its administration to eight conscious dogs by measurement of the intravenous dose of acetylstrophanthidin necessary to induce toxic changes in the ECG. Acetyl-strophanthidin was used because its rapid elimination from the body permitted estimates to be made 45, 180 and 360 min after digoxin administration. 2 Each dog underwent four studies in which doses of 0.05, 0.1, 0.2 and 0.4 mg/kg digoxin were used in a randomized sequence allowing at least ten days between each dose. 3 Digoxin reduced the amount of acetylstrophanthidin required to cause toxic changes in the ECG; this increase in cardiac sensitivity was dose-dependent. 4 There was no correlation between plasma levels of digoxin and the tendency to dysrhythmia, since peak plasma concentrations of digoxin were reached at about 60 min after dosing whereas maximal sensitivity to acetylstrophanthidin was found 3 to 6 h after administration of digoxin. 5 These results suggest that there is little or no increased risk of cardiotoxicity during periods of transient increase in plasma levels of digoxin.", "contents": "The relationship between cardiotoxicity and plasma digoxin concentration in conscious dogs. 1 The tendency of a given oral dose of digoxin to induce cardiac dysrhythmia was determined indirectly at various times after its administration to eight conscious dogs by measurement of the intravenous dose of acetylstrophanthidin necessary to induce toxic changes in the ECG. Acetyl-strophanthidin was used because its rapid elimination from the body permitted estimates to be made 45, 180 and 360 min after digoxin administration. 2 Each dog underwent four studies in which doses of 0.05, 0.1, 0.2 and 0.4 mg/kg digoxin were used in a randomized sequence allowing at least ten days between each dose. 3 Digoxin reduced the amount of acetylstrophanthidin required to cause toxic changes in the ECG; this increase in cardiac sensitivity was dose-dependent. 4 There was no correlation between plasma levels of digoxin and the tendency to dysrhythmia, since peak plasma concentrations of digoxin were reached at about 60 min after dosing whereas maximal sensitivity to acetylstrophanthidin was found 3 to 6 h after administration of digoxin. 5 These results suggest that there is little or no increased risk of cardiotoxicity during periods of transient increase in plasma levels of digoxin."} {"id": "PMID:1276539", "title": "Emetine myopathy in the rat.", "content": "1 (-)Emetine (0.25-2.0 mg/kg i.p.) was administered to rats for up to 220 days. 2 At doses of 1.0 mg/kg or less, the animals continued to gain weight but more slowly than the untreated control animals. The physiological changes in the muscles from these animals were minimal; there was a small reduction in both the resting membrane potential and in the maximum rate of rise of the action potential. There was no atrophy or loss of muscle fibres although in the occasional muscle, hyaline fibres, necrotic fibres and split fibres were observed. There was a focal loss of myofibrillar adenosine triphosphatase (ATPase) and nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) in Type II and Type III fibres, but no such loss in Type I fibres. 3 The animals receiving 2.0 mg/kg of (-)emetine gained weight slowly for up to 20 days but then rapidly lost weight and by 30 days they were weak and emaciated. The muscles from these animals were severly atrophied and the total muscle wet weight was reduced by almost 20%. 4 The strength of the muscles from these animals was measured in vitro using direct stimulation. They were weaker than normal both in absolute terms and when expressed in terms of tension developed/unit wet weight. 5 There was no evidence of either functional or structural denervation but surgically denervated muscles from animals in this group were indistinguishable from denervated muscles from normal rats. 6 Severe structural damage was obvious in the fibres of both extensor digitorum longus and soleus. Necrotic, hyaline and splitting fibres were common and the focal loss of myofibrillar ATPase and NADH-TR activity was extensive and occurred in Type I fibres as well as in Type II and Type II fibres. 7 It is concluded that the muscular weakness induced by (-)-emetine is due to a direct effect on the muscle fibres and that this occurs at a subcellular level. There is no evidence that functional or structural denervation plays any role in the aetiology of emetine myopathy in the rat.", "contents": "Emetine myopathy in the rat. 1 (-)Emetine (0.25-2.0 mg/kg i.p.) was administered to rats for up to 220 days. 2 At doses of 1.0 mg/kg or less, the animals continued to gain weight but more slowly than the untreated control animals. The physiological changes in the muscles from these animals were minimal; there was a small reduction in both the resting membrane potential and in the maximum rate of rise of the action potential. There was no atrophy or loss of muscle fibres although in the occasional muscle, hyaline fibres, necrotic fibres and split fibres were observed. There was a focal loss of myofibrillar adenosine triphosphatase (ATPase) and nicotinamide adenine dinucleotide tetrazolium reductase (NADH-TR) in Type II and Type III fibres, but no such loss in Type I fibres. 3 The animals receiving 2.0 mg/kg of (-)emetine gained weight slowly for up to 20 days but then rapidly lost weight and by 30 days they were weak and emaciated. The muscles from these animals were severly atrophied and the total muscle wet weight was reduced by almost 20%. 4 The strength of the muscles from these animals was measured in vitro using direct stimulation. They were weaker than normal both in absolute terms and when expressed in terms of tension developed/unit wet weight. 5 There was no evidence of either functional or structural denervation but surgically denervated muscles from animals in this group were indistinguishable from denervated muscles from normal rats. 6 Severe structural damage was obvious in the fibres of both extensor digitorum longus and soleus. Necrotic, hyaline and splitting fibres were common and the focal loss of myofibrillar ATPase and NADH-TR activity was extensive and occurred in Type I fibres as well as in Type II and Type II fibres. 7 It is concluded that the muscular weakness induced by (-)-emetine is due to a direct effect on the muscle fibres and that this occurs at a subcellular level. There is no evidence that functional or structural denervation plays any role in the aetiology of emetine myopathy in the rat."} {"id": "PMID:1276540", "title": "Effects of amino acids and convulsants on spontaneous action potentials in cerebellar cortex slices.", "content": "1 Picrotoxin selectively and reversibly suppressed the inhibitory action of gamma-aminobutyric acid (GABA), but not that of glycine, taurine or beta-alanine, on the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or beta-alanine but had no effect on that of GABA. 2 GABA, glycine, taurine and beta-alanine showed an early excitatory effect that was unaffected by picrotoxin or strychnine. 3 Studies of the dose-response relations indicated a competition between the amino acid and the convulsant at a common receptor site. 4 Kinetic analyses of the dose-response relations for the amino acids in the presence or absence of picrotoxin or strychnine indicated that the number of molecules of amino acid combining with the receptor site in order to produce a response (inhibition or excitation) was 3 for GABA, 2 for glycine, 3 for taurine and 4 for beta-alanine. There appeared to be no evidence that the response was due to the cooperativity between the amino acid receptor complexes. The number of molecules of convulsant that combined with the receptor site was 1 for either strychnine or picrotoxin. 5 Mixtures of glycine with taurine or beta-alanine, in contrast to those with GABA, appeared not to give additive inhibitory effects.", "contents": "Effects of amino acids and convulsants on spontaneous action potentials in cerebellar cortex slices. 1 Picrotoxin selectively and reversibly suppressed the inhibitory action of gamma-aminobutyric acid (GABA), but not that of glycine, taurine or beta-alanine, on the frequency of spontaneous spike discharges in guinea-pig cerebellar slices. Strychnine reversibly suppressed the inhibitory action of glycine, taurine or beta-alanine but had no effect on that of GABA. 2 GABA, glycine, taurine and beta-alanine showed an early excitatory effect that was unaffected by picrotoxin or strychnine. 3 Studies of the dose-response relations indicated a competition between the amino acid and the convulsant at a common receptor site. 4 Kinetic analyses of the dose-response relations for the amino acids in the presence or absence of picrotoxin or strychnine indicated that the number of molecules of amino acid combining with the receptor site in order to produce a response (inhibition or excitation) was 3 for GABA, 2 for glycine, 3 for taurine and 4 for beta-alanine. There appeared to be no evidence that the response was due to the cooperativity between the amino acid receptor complexes. The number of molecules of convulsant that combined with the receptor site was 1 for either strychnine or picrotoxin. 5 Mixtures of glycine with taurine or beta-alanine, in contrast to those with GABA, appeared not to give additive inhibitory effects."} {"id": "PMID:1276541", "title": "Effects of some purine derivatives on the guinea-pig trachea and their interaction with drugs that block adenosine uptake.", "content": "1 Adenosine, adenosine 5'-triphosphate (ATP), adenine, inosine and guanosine all caused concentration-dependent relaxations of guinea-pig tracheal smooth muscle in vitro. The relative potencies in descending order were: adenine greater than or equal to guanosine greater than inosine greater than or equal to adenosine greater than or equal to ATP. 2 Responses to the purine compounds were unaffected by propranolol (1 mug/ml). 3 The spasmolytic potencies of adenosine and ATP were greatly enhanced in the presence of the adenosine uptake blocking drugs dipyridamole, hexobendine or Dilazep, whereas responses to adenine were unaffected and those to inosine and guanosine were reduced. 4 The spasmolytic potencies of noradrenaline, aminophylline, prostaglandin E2 and glyceryl trinitrate were unaffected by dipyridamole, hexobendine and Dilazep. 5 It is suggested that an adenosine uptake process may exist in the trachea of the guinea-pig and that this process is inhibited by dipyridamole, hexobendine and Dilazep.", "contents": "Effects of some purine derivatives on the guinea-pig trachea and their interaction with drugs that block adenosine uptake. 1 Adenosine, adenosine 5'-triphosphate (ATP), adenine, inosine and guanosine all caused concentration-dependent relaxations of guinea-pig tracheal smooth muscle in vitro. The relative potencies in descending order were: adenine greater than or equal to guanosine greater than inosine greater than or equal to adenosine greater than or equal to ATP. 2 Responses to the purine compounds were unaffected by propranolol (1 mug/ml). 3 The spasmolytic potencies of adenosine and ATP were greatly enhanced in the presence of the adenosine uptake blocking drugs dipyridamole, hexobendine or Dilazep, whereas responses to adenine were unaffected and those to inosine and guanosine were reduced. 4 The spasmolytic potencies of noradrenaline, aminophylline, prostaglandin E2 and glyceryl trinitrate were unaffected by dipyridamole, hexobendine and Dilazep. 5 It is suggested that an adenosine uptake process may exist in the trachea of the guinea-pig and that this process is inhibited by dipyridamole, hexobendine and Dilazep."} {"id": "PMID:1276542", "title": "Concentration of (+/-)-propranolol in isolated, perfused lungs of rat.", "content": "1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation.", "contents": "Concentration of (+/-)-propranolol in isolated, perfused lungs of rat. 1 The metabolism and the accumulation of (+/-)-propranolol have been studied in isolated lungs of the rat, perfused with an artificial medium. 2 Little or no metabolism took place during the perfusion periods (up to 10 minutes). 3 Accumulation was observed with high tissue/medium ratios for substrate concentrations of 0.2 muM to 1 mM; there was evidence for saturability, but no real plateau could be seen. The presence of two binding sites with different affinities was established. 4 Cold greatly inhibited the accumulation process at low substrate concentrations, but had no effect at 1 mM propranolol. 5 Inhibition of accumulation was measured in the presence of imipramine, desmethylimipramine, nortryptiline, chlorpromazine and of Na+-free medium. Cocaine, 5-hydroxytryptamine and noradrenaline had no effect. Lidocaine enhanced the accumulation process. Release of previously bound propranolol was accelerated in the presence of propranolol and imipramine, unaffected by a Na+-free medium and decreased by cold and by lidocaine. 6 Experiments on lung tissue slices yielded qualitatively similar results to those obtained with perfused lungs. Ouabain and KCN had no or little effect on propranolol accumulation."} {"id": "PMID:1276543", "title": "Indirect effects of amino-acids on sympathetic ganglion cells mediated through the release of gamma-aminobutyric acid from glial cells.", "content": "1 All experiments were performed on rat isolated desheathed superior cervical ganglia maintained in Krebs solution containing amino-oxyacetic acid (10 muM) at 25 degrees C. 2 Influx rates of gamma-amino-n-butyric acid (GABA) were measured by incubating ganglia in 0.5 muM [3H]-GABA for 30 minutes. Influx was inhibited by 50% on adding 14.3 muM unlabelled GABA, 59.2 muM beta-alanine (BALA) or 424 muM beta-amino-n-butyric acid (BABA). 3 Efflux of [3H]-GABA into non-radioactive solution superfused over ganglia previously incubated for 60 min in 1 muM [3H]-GABA was measured. The mean resting efflux rate coefficient (k) was 0.64 +/- 0.05 X 10(-3) min-1. Addition of high concentrations of unlabelled GABA, BABA or BALA to the superfusing solution increased k by (maximally) 3.6-4.3 times; half-maximal increases occurred at the following concentrations: GABA, 16 muM; BALA, 85 muM; BABA, 606 muM. Replacement of external Na+ with Li+ or TRIS increased the resting value of k and inhibited acceleration by external amino acids. Prior incubation in 1 muM [3H]-GABA with 1 mM unlabelled GABA increased resting k 1.5 times, but did not alter the peak rate coefficient produced by external amino acids. 4 Neuronal depolarization produced by the amino acids was measured with surface electrodes. Pre-incubation in 1 mM GABA for 60 min potentiated low-amplitude responses to BALA or BABA but not those to GABA or 3-aminopropanesulphonic acid (a potent agonist with low affinity for the GABA carrier). Omission of external Na+ reduced responses to BABA but increased those to GABA. 5 Incubation in 1 mM GABA for 60 min (as required to potentiate BABA or BALA actions) increased the amount of GABA in the tissue from 0.21 to 0.73 mmol/kg wet weight. Autoradiographs in which labelled GABA was used indicated that uptake into neuroglial cells was responsible for this accumulation. 6 It is suggested that: (i) BALA and BABA are substrates for the inward GABA carrier responsible for GABA entry into ganglionic glial cells; (ii) they accelerate efflux by inhibiting carrier-mediated reaccumulation of effluent GABA by the glial cells; (iii) interstitial GABA concentrations are thereby increased to a level capable of depolarizing adjacent neurones; and (iv) this, rather than direct GABA-receptor activation, accounts for the depolarization produced by low concentrations of BALA and BABA. Potentiation of their depolarizing action after pre-incubation in 1 mM GABA is suggested to result from the increased amount of intracellular GABA available for release, and is quantitatively compatible with this increase; inhibition in Na+-free solution is due to their inability to inhibit reaccumulation of GABA under these conditions. 7 A model for the action of carrier substrates is described in an Appendix. Calculations based thereon yield increments in interstitial GABA concentration in the presence of carrier substrates compatible with those determined experimentally (up to 1 muM at rest or 3.4 muM after pre-incubation in GABA).", "contents": "Indirect effects of amino-acids on sympathetic ganglion cells mediated through the release of gamma-aminobutyric acid from glial cells. 1 All experiments were performed on rat isolated desheathed superior cervical ganglia maintained in Krebs solution containing amino-oxyacetic acid (10 muM) at 25 degrees C. 2 Influx rates of gamma-amino-n-butyric acid (GABA) were measured by incubating ganglia in 0.5 muM [3H]-GABA for 30 minutes. Influx was inhibited by 50% on adding 14.3 muM unlabelled GABA, 59.2 muM beta-alanine (BALA) or 424 muM beta-amino-n-butyric acid (BABA). 3 Efflux of [3H]-GABA into non-radioactive solution superfused over ganglia previously incubated for 60 min in 1 muM [3H]-GABA was measured. The mean resting efflux rate coefficient (k) was 0.64 +/- 0.05 X 10(-3) min-1. Addition of high concentrations of unlabelled GABA, BABA or BALA to the superfusing solution increased k by (maximally) 3.6-4.3 times; half-maximal increases occurred at the following concentrations: GABA, 16 muM; BALA, 85 muM; BABA, 606 muM. Replacement of external Na+ with Li+ or TRIS increased the resting value of k and inhibited acceleration by external amino acids. Prior incubation in 1 muM [3H]-GABA with 1 mM unlabelled GABA increased resting k 1.5 times, but did not alter the peak rate coefficient produced by external amino acids. 4 Neuronal depolarization produced by the amino acids was measured with surface electrodes. Pre-incubation in 1 mM GABA for 60 min potentiated low-amplitude responses to BALA or BABA but not those to GABA or 3-aminopropanesulphonic acid (a potent agonist with low affinity for the GABA carrier). Omission of external Na+ reduced responses to BABA but increased those to GABA. 5 Incubation in 1 mM GABA for 60 min (as required to potentiate BABA or BALA actions) increased the amount of GABA in the tissue from 0.21 to 0.73 mmol/kg wet weight. Autoradiographs in which labelled GABA was used indicated that uptake into neuroglial cells was responsible for this accumulation. 6 It is suggested that: (i) BALA and BABA are substrates for the inward GABA carrier responsible for GABA entry into ganglionic glial cells; (ii) they accelerate efflux by inhibiting carrier-mediated reaccumulation of effluent GABA by the glial cells; (iii) interstitial GABA concentrations are thereby increased to a level capable of depolarizing adjacent neurones; and (iv) this, rather than direct GABA-receptor activation, accounts for the depolarization produced by low concentrations of BALA and BABA. Potentiation of their depolarizing action after pre-incubation in 1 mM GABA is suggested to result from the increased amount of intracellular GABA available for release, and is quantitatively compatible with this increase; inhibition in Na+-free solution is due to their inability to inhibit reaccumulation of GABA under these conditions. 7 A model for the action of carrier substrates is described in an Appendix. Calculations based thereon yield increments in interstitial GABA concentration in the presence of carrier substrates compatible with those determined experimentally (up to 1 muM at rest or 3.4 muM after pre-incubation in GABA)."} {"id": "PMID:1276544", "title": "The inhibition by glucagon of the vasoconstrictor actions of noradrenaline, angiotensin and vasopressin on the hepatic arterial vascular bed of the dog.", "content": "1 The hepatic artery of the anaesthetized dog was cannulated and perfused from a femoral artery, the blood flow and perfusion pressure being monitored continuously. The sympathetic periarterial nerves were divided. 2 Dose-dependent increases in hepatic arterial vascular resistance (HAVR) resulted from intra-arterial injections of noradrenaline, angiotensin and vasopressin. 3 Single injections of glucagon (100 mug, i.a.) caused a transient significant fall in HAVR of 19.9 +/- 3.2%, and infusions of 25 mug/min of glucagon intra-arterially caused maintained reductions in HAVR of 16.9 +/- 4.2%. 4 After single injections of 100 mug glucagon intra-arterially the vasoconstrictor responses to noradrenaline, angiotensin, and vasopressin were reduced by about 85-95%. Recovery occurred in 8-10 minutes. 5 Intra-arterial infusions of glucagon, 2.5-50.0 mug/min, reduced the effects of test doses of noradrenaline, angiotensin and vasopressin throughout the period of the infusions. 6 Dose-response curves to the constrictor agents were constructed before, during and after intra-arterial infusions of 25 mug/min of glucagon. Glucagon caused a parallel shift of the curves for noradrenaline and angiotensin to the right, with no suppression of the maximum response. 7 Infusions of glucagon shifted the dose-response curve for vasopressin to the right, but, in contrast to noradrenaline and angiotensin, the shift was nonparallel and there was a suppression of the maximum response by about one-half. 8 A large dose of insulin, 10 iu, transiently reduced HAVR and caused a weak and very transient inhibition of the effect of test doses of noradrenaline. The characteristics of these effects were quite different from those of glucagon. 9 It is possible that the antagonism by glucagon of the vasoconstrictor responses of the hepatic arterial vasculature may be important in protecting this vascular bed from the effects of concomitantly released vasoconstrictor agents.", "contents": "The inhibition by glucagon of the vasoconstrictor actions of noradrenaline, angiotensin and vasopressin on the hepatic arterial vascular bed of the dog. 1 The hepatic artery of the anaesthetized dog was cannulated and perfused from a femoral artery, the blood flow and perfusion pressure being monitored continuously. The sympathetic periarterial nerves were divided. 2 Dose-dependent increases in hepatic arterial vascular resistance (HAVR) resulted from intra-arterial injections of noradrenaline, angiotensin and vasopressin. 3 Single injections of glucagon (100 mug, i.a.) caused a transient significant fall in HAVR of 19.9 +/- 3.2%, and infusions of 25 mug/min of glucagon intra-arterially caused maintained reductions in HAVR of 16.9 +/- 4.2%. 4 After single injections of 100 mug glucagon intra-arterially the vasoconstrictor responses to noradrenaline, angiotensin, and vasopressin were reduced by about 85-95%. Recovery occurred in 8-10 minutes. 5 Intra-arterial infusions of glucagon, 2.5-50.0 mug/min, reduced the effects of test doses of noradrenaline, angiotensin and vasopressin throughout the period of the infusions. 6 Dose-response curves to the constrictor agents were constructed before, during and after intra-arterial infusions of 25 mug/min of glucagon. Glucagon caused a parallel shift of the curves for noradrenaline and angiotensin to the right, with no suppression of the maximum response. 7 Infusions of glucagon shifted the dose-response curve for vasopressin to the right, but, in contrast to noradrenaline and angiotensin, the shift was nonparallel and there was a suppression of the maximum response by about one-half. 8 A large dose of insulin, 10 iu, transiently reduced HAVR and caused a weak and very transient inhibition of the effect of test doses of noradrenaline. The characteristics of these effects were quite different from those of glucagon. 9 It is possible that the antagonism by glucagon of the vasoconstrictor responses of the hepatic arterial vasculature may be important in protecting this vascular bed from the effects of concomitantly released vasoconstrictor agents."} {"id": "PMID:1276546", "title": "Heroin misuse and delinquency in a new town.", "content": "The subjects of this study were eighty misusers of heroin who lived in the New Town of Crawley, West Sussex. The relationship between their criminal histories and their histories of drug misuse were examined. It was found that more of the heroin misusers than would be expected had been convicted of criminal offenses before they began to misuse drugs, while the reduction or cessation of heroin use during a four-year follow-up period was accompanied by a reduction in convictions. Some social characteristics of the male heroin misusers were compared with those of two other Crawley groups--a group of juvenile offenders who did not misuse heroin and their control group of non-delinquents. Characteristics commonly associated with maladjustment did not distinguish the heroin misusers from the juvenile offenders, nor were they found to be associated with the continued use of heroin. Analysis of the data in epidemiological terms suggested that among the necessary conditions for an outbreak of drug misuse in a particular community the availability of drugs together with socializing drug users were more important than the presence of predisposed individuals.", "contents": "Heroin misuse and delinquency in a new town. The subjects of this study were eighty misusers of heroin who lived in the New Town of Crawley, West Sussex. The relationship between their criminal histories and their histories of drug misuse were examined. It was found that more of the heroin misusers than would be expected had been convicted of criminal offenses before they began to misuse drugs, while the reduction or cessation of heroin use during a four-year follow-up period was accompanied by a reduction in convictions. Some social characteristics of the male heroin misusers were compared with those of two other Crawley groups--a group of juvenile offenders who did not misuse heroin and their control group of non-delinquents. Characteristics commonly associated with maladjustment did not distinguish the heroin misusers from the juvenile offenders, nor were they found to be associated with the continued use of heroin. Analysis of the data in epidemiological terms suggested that among the necessary conditions for an outbreak of drug misuse in a particular community the availability of drugs together with socializing drug users were more important than the presence of predisposed individuals."} {"id": "PMID:1276547", "title": "Psychiatric problems in systemic lupus erythematosus.", "content": "Four patients with systemic lupus erythematosus (SLE) are described in whom there were major psychiatric complications. Two of these patients had cerebral lupus with psychiatric manifestations of the disease together with other features of disease activity and responding to treatment with high dose steroids. The first of these had had a ten-year history of recurrent episodes of depression before other features of the disease became evident; in the second patient recurrent psychotic episodes occurred after the onset of typical multi-system disease. The third patient had had a minor cerebro-vascular accident four years before other features of SLE became manifest, and cerebral deterioration later on in her life was probably due to hypertensive cerebro-vascular disease secondary to the renal disease of SLE. The fourth patient, a young man, had had recurrent episodes of depression and aggressive behaviour for several years and committed suicide at the age of 33.", "contents": "Psychiatric problems in systemic lupus erythematosus. Four patients with systemic lupus erythematosus (SLE) are described in whom there were major psychiatric complications. Two of these patients had cerebral lupus with psychiatric manifestations of the disease together with other features of disease activity and responding to treatment with high dose steroids. The first of these had had a ten-year history of recurrent episodes of depression before other features of the disease became evident; in the second patient recurrent psychotic episodes occurred after the onset of typical multi-system disease. The third patient had had a minor cerebro-vascular accident four years before other features of SLE became manifest, and cerebral deterioration later on in her life was probably due to hypertensive cerebro-vascular disease secondary to the renal disease of SLE. The fourth patient, a young man, had had recurrent episodes of depression and aggressive behaviour for several years and committed suicide at the age of 33."} {"id": "PMID:1276548", "title": "Crohn's disease: a psychosomatic illness?", "content": "We investigated the psychological status of Crohn's disease patients because 10 such patients had been referred to our psychiatric out-patient department over a period of six years, whereas if there were no association between the disease and psychiatric morbidity, the expected referral rate would be one case in 20 to 100 years. We found an association between episodes of psychiatric and physical symptoms in the case histories. We administered the Eysenck Personality Inventory and the Manifest Anxiety Scale to 28 out-patients with Crohn's disease (8 psychiatrically and 20 non-psychiatrically referred), 17 with chronic non-psychosomatic medical diseases, 43 with psychosomatic diseases and 100 with neurosis. Crohn's disease patients were significantly more anxious, neurotic and introverted than both the test norms and the non-psychosomatic medical out-patients and did not differ appreciably from the psychosomatic patients in these respect.", "contents": "Crohn's disease: a psychosomatic illness? We investigated the psychological status of Crohn's disease patients because 10 such patients had been referred to our psychiatric out-patient department over a period of six years, whereas if there were no association between the disease and psychiatric morbidity, the expected referral rate would be one case in 20 to 100 years. We found an association between episodes of psychiatric and physical symptoms in the case histories. We administered the Eysenck Personality Inventory and the Manifest Anxiety Scale to 28 out-patients with Crohn's disease (8 psychiatrically and 20 non-psychiatrically referred), 17 with chronic non-psychosomatic medical diseases, 43 with psychosomatic diseases and 100 with neurosis. Crohn's disease patients were significantly more anxious, neurotic and introverted than both the test norms and the non-psychosomatic medical out-patients and did not differ appreciably from the psychosomatic patients in these respect."} {"id": "PMID:1276549", "title": "'Filtering' and the cognitive deficit in schizophrenia.", "content": "This study attempted to clarify the nature of dysfunction in the selective attention of schizophrenics. Within the framework of Broadbent's (1971) theory of information processing it was argued that 'filtering' inefficiency should be reflected in a reduction in the discrepancy in performance on a short-term memory task between the condition of pre-instruction as to the relevant material and that of post-instruction. Three groups of subjects, 10 schizophrenics, 10 depressives, and 10 normals, matched for age and intelligence were tested on such a task. While the overall performance of normal subjects was superior to that of both psychiatric groups, depressives and schizophrenics did not differ. The normal group also showed a significantly greater improvement with pre-instruction than the psychiatric groups; again, the schizophrenics and depressives did not differ significantly, though there was a tendency for schizophrenics to benefit less than depressives from pre-instruction. It appears that 'filtering' difficulties as here defined may not be specific to schizophrenia. Alternative conceptualizations of the cognitive abnormalities shown by schizophrenics, such as slowness of information processing and difficulties in response selection, may be more useful.", "contents": "'Filtering' and the cognitive deficit in schizophrenia. This study attempted to clarify the nature of dysfunction in the selective attention of schizophrenics. Within the framework of Broadbent's (1971) theory of information processing it was argued that 'filtering' inefficiency should be reflected in a reduction in the discrepancy in performance on a short-term memory task between the condition of pre-instruction as to the relevant material and that of post-instruction. Three groups of subjects, 10 schizophrenics, 10 depressives, and 10 normals, matched for age and intelligence were tested on such a task. While the overall performance of normal subjects was superior to that of both psychiatric groups, depressives and schizophrenics did not differ. The normal group also showed a significantly greater improvement with pre-instruction than the psychiatric groups; again, the schizophrenics and depressives did not differ significantly, though there was a tendency for schizophrenics to benefit less than depressives from pre-instruction. It appears that 'filtering' difficulties as here defined may not be specific to schizophrenia. Alternative conceptualizations of the cognitive abnormalities shown by schizophrenics, such as slowness of information processing and difficulties in response selection, may be more useful."} {"id": "PMID:1276550", "title": "A job rating scale for use in psychiatric rehabilitation.", "content": "Work has been a highly valued feature of psychiatric rehabilitation programmes. The performance of patients has often been the object of scrutiny and assessment, but the jobs performed by these patients have not been so assessed. This paper describes the development and use of a job rating scale which parallels the use of patient assessment instruments.", "contents": "A job rating scale for use in psychiatric rehabilitation. Work has been a highly valued feature of psychiatric rehabilitation programmes. The performance of patients has often been the object of scrutiny and assessment, but the jobs performed by these patients have not been so assessed. This paper describes the development and use of a job rating scale which parallels the use of patient assessment instruments."} {"id": "PMID:1276551", "title": "Influence of coroners' officers and pathologists on suicide verdicts.", "content": "Three-hundred-and-thirty cases of unnatural death, leading to 110 open verdicts, 110 verdicts of suicide and 110 of accident, from the Inner West London Coroner's District have been examined to see if particular coroner's officers or pathologists were associated with disproportionate numbers of suicide verdicts. No significant deviations from the expected numbers were found. Coroner's officers probably share common ideas about the features defining suicide, and so do pathologists.", "contents": "Influence of coroners' officers and pathologists on suicide verdicts. Three-hundred-and-thirty cases of unnatural death, leading to 110 open verdicts, 110 verdicts of suicide and 110 of accident, from the Inner West London Coroner's District have been examined to see if particular coroner's officers or pathologists were associated with disproportionate numbers of suicide verdicts. No significant deviations from the expected numbers were found. Coroner's officers probably share common ideas about the features defining suicide, and so do pathologists."} {"id": "PMID:1276552", "title": "Monosymptomatic hypochondriasis, abnormal illness behaviour and suicide.", "content": "Two cases of chronic monosymptomatic psychogenic eye pain with abnormal illness behaviour are presented. Both failed to respond to a wide variety of treatments, and despite the accepted low suicidal risk in hypochondriasis both killed themselves. The origin, prognosis and therapy of such behaviour are discussed in this context.", "contents": "Monosymptomatic hypochondriasis, abnormal illness behaviour and suicide. Two cases of chronic monosymptomatic psychogenic eye pain with abnormal illness behaviour are presented. Both failed to respond to a wide variety of treatments, and despite the accepted low suicidal risk in hypochondriasis both killed themselves. The origin, prognosis and therapy of such behaviour are discussed in this context."} {"id": "PMID:1276553", "title": "A comparison between the Hamilton Rating Scale and the Beck Inventory in the measurement of depression.", "content": "Correlations were made between ratings on the Hamilton Rating Scale for depression and the Inventory for measuring depression devised by Beck. Satisfactory and significant correlations were observed in only two-thirds of the patients, and often very divergent results were found in the remaining third.", "contents": "A comparison between the Hamilton Rating Scale and the Beck Inventory in the measurement of depression. Correlations were made between ratings on the Hamilton Rating Scale for depression and the Inventory for measuring depression devised by Beck. Satisfactory and significant correlations were observed in only two-thirds of the patients, and often very divergent results were found in the remaining third."} {"id": "PMID:1276554", "title": "Dyskinesias associated with tricyclic antidepressants.", "content": "Hyperkinetic movement disorders may occur as side effects of antipsychotic drugs; and a hyperdopaminergic state induced by the neuroleptic compounds is thought to be a cause of extrapyramidal disorders such as tardive dyskinesia. We have observed two cases of the dyskinetic syndrome in patients receiving tricyclic antidepressants (TCA). Because the TCA are known to have little effect on striatal dopamine but do share with the neuroleptics potent anticholinergic activity, these cases appear to support the hypothesis that the drug-induced hyperkinetic disorders are related to a diminution of CNS acetylcholine activity as well as to an increase in dopamine activity.", "contents": "Dyskinesias associated with tricyclic antidepressants. Hyperkinetic movement disorders may occur as side effects of antipsychotic drugs; and a hyperdopaminergic state induced by the neuroleptic compounds is thought to be a cause of extrapyramidal disorders such as tardive dyskinesia. We have observed two cases of the dyskinetic syndrome in patients receiving tricyclic antidepressants (TCA). Because the TCA are known to have little effect on striatal dopamine but do share with the neuroleptics potent anticholinergic activity, these cases appear to support the hypothesis that the drug-induced hyperkinetic disorders are related to a diminution of CNS acetylcholine activity as well as to an increase in dopamine activity."} {"id": "PMID:1276559", "title": "Psychiatric priorities in developing countries.", "content": "Many psychiatrists assert that an expansion of mental health services in the developing countries is overdue. This will only take place if: (i) the tasks of mental health care are undertaken by a wide range of non-specialist health workers, including those responsible for primary health care; and (ii) services are directed initially at a very limited range of priority conditions. The method of priority selection is discussed, and the process required for translation of priority decisions into health action is exemplified by two illustrations.", "contents": "Psychiatric priorities in developing countries. Many psychiatrists assert that an expansion of mental health services in the developing countries is overdue. This will only take place if: (i) the tasks of mental health care are undertaken by a wide range of non-specialist health workers, including those responsible for primary health care; and (ii) services are directed initially at a very limited range of priority conditions. The method of priority selection is discussed, and the process required for translation of priority decisions into health action is exemplified by two illustrations."} {"id": "PMID:1276560", "title": "A clinical evaluation of depressives found in a rural survey in India.", "content": "Those who were labelled as depressives in a rural survey were randomly divided into a Medicine group (who received antidepressive drug treatment), a Placebo group (who received placebo) and a Natural Process group (who received no treatment). The depth of their depression was assessed by Hamilton's Depressive Rating Scale before the beginning of the trial, on the 14th day and on the 28th day of trial. They were compared with a matched group of healthy controls and again with a matched group of depressives who attended an urban clinic for treatment. The results indicate that the rural depressives who never sought treatment voluntarily were not different from those who sought treatment in clinics, so far as their response to treatment is concerned.", "contents": "A clinical evaluation of depressives found in a rural survey in India. Those who were labelled as depressives in a rural survey were randomly divided into a Medicine group (who received antidepressive drug treatment), a Placebo group (who received placebo) and a Natural Process group (who received no treatment). The depth of their depression was assessed by Hamilton's Depressive Rating Scale before the beginning of the trial, on the 14th day and on the 28th day of trial. They were compared with a matched group of healthy controls and again with a matched group of depressives who attended an urban clinic for treatment. The results indicate that the rural depressives who never sought treatment voluntarily were not different from those who sought treatment in clinics, so far as their response to treatment is concerned."} {"id": "PMID:1276561", "title": "Attempted suicide among Asian immigrants in Birmingham.", "content": "This retrospective study describes the epidemiology of attempted suicide among Asian (Bangladesh, India and Pakistan) immigrants in Birmingham during the period 1969-1972. The hypothesis of no difference in the distribution of attempted suicide among native and immigrant groups was not upheld. The immigrant group was under-represented among all the admissions to Birmingham's hospitals. It is estimated that the crude adjusted rates for attempted suicide among the male and female Asian immigrants aged 15-64 years are 57 and 126 per 100,000 population per annum respectively. These are lower than the rates found among natives in Britain, but the female immigrant rate is higher than that found in India. Asian patients who attempt suicide in India and Birmingham are younger than 45 years of age, rarely abuse drugs and alcohol, and make repeated attempts infrequently. In Birmingham, however, immigrants and native patients swallow similar, mostly psychotropic, tablets and not insecticides as in India. It is noteworthy that an interpersonal dispute precedes attempted suicide more frequently among immigrant patients than among native ones in either area.", "contents": "Attempted suicide among Asian immigrants in Birmingham. This retrospective study describes the epidemiology of attempted suicide among Asian (Bangladesh, India and Pakistan) immigrants in Birmingham during the period 1969-1972. The hypothesis of no difference in the distribution of attempted suicide among native and immigrant groups was not upheld. The immigrant group was under-represented among all the admissions to Birmingham's hospitals. It is estimated that the crude adjusted rates for attempted suicide among the male and female Asian immigrants aged 15-64 years are 57 and 126 per 100,000 population per annum respectively. These are lower than the rates found among natives in Britain, but the female immigrant rate is higher than that found in India. Asian patients who attempt suicide in India and Birmingham are younger than 45 years of age, rarely abuse drugs and alcohol, and make repeated attempts infrequently. In Birmingham, however, immigrants and native patients swallow similar, mostly psychotropic, tablets and not insecticides as in India. It is noteworthy that an interpersonal dispute precedes attempted suicide more frequently among immigrant patients than among native ones in either area."} {"id": "PMID:1276562", "title": "Attempted suicide among the Irish-born population in birmingham.", "content": "The epidemiology of attempted suicide among Irish immigrants in Birmingham is described from data concerning 352 (138 male, 214 female) hospital admissions made during the period 1969 to 1972. Admissions from the Irish Republic and from Northern Ireland were similarly distributed, but were both grossly over-represented. The average annual rate of admission (222 male, 362 female) was probably higher than the rates in Dublin, Belfast and Edinburgh. The female patient rate (286) was greater than that of Edinburgh, but the male rate (143) was not. Fewer Irish than British admissions gave a history of previous attempted suicide or repeated this attempt. Indices of stress among immigrants were, however, greater. The importance of socio-cultural factors is discussed.", "contents": "Attempted suicide among the Irish-born population in birmingham. The epidemiology of attempted suicide among Irish immigrants in Birmingham is described from data concerning 352 (138 male, 214 female) hospital admissions made during the period 1969 to 1972. Admissions from the Irish Republic and from Northern Ireland were similarly distributed, but were both grossly over-represented. The average annual rate of admission (222 male, 362 female) was probably higher than the rates in Dublin, Belfast and Edinburgh. The female patient rate (286) was greater than that of Edinburgh, but the male rate (143) was not. Fewer Irish than British admissions gave a history of previous attempted suicide or repeated this attempt. Indices of stress among immigrants were, however, greater. The importance of socio-cultural factors is discussed."} {"id": "PMID:1276563", "title": "How common is anorexia nervosa? A prevalence study.", "content": "During 1972-74 nine populations of schoolgirls were surveyed in respect of the occurrence of anorexia nervosa. As well as the current school year, previous years (going back variously 3-6 years) were also carefully studied within seven of the schools. Anorexia nervosa was only identified as present or having been present if the diagnosis was unequivocal: for instance, seemingly evident and severe cases which could not be traced were excluded. The condition in severe form was found to be relatively common in the independent sector of education, probably implying a social class factor. In all such schools, the prevalence was one severe case in approximately every 200 girls. In those aged 16 and over it amounted to one severe case in about every 100 girls. Overall, these schools encountered one 'new' severe case in every 250 pupils aged 16 years and over. The condition is likely to be even more common than this study allows because of the stringent limits set here on inclusion of cases and the age-bands studied. It is concluded that severe anorexia nervosa is a common condition and is probably getting more common.", "contents": "How common is anorexia nervosa? A prevalence study. During 1972-74 nine populations of schoolgirls were surveyed in respect of the occurrence of anorexia nervosa. As well as the current school year, previous years (going back variously 3-6 years) were also carefully studied within seven of the schools. Anorexia nervosa was only identified as present or having been present if the diagnosis was unequivocal: for instance, seemingly evident and severe cases which could not be traced were excluded. The condition in severe form was found to be relatively common in the independent sector of education, probably implying a social class factor. In all such schools, the prevalence was one severe case in approximately every 200 girls. In those aged 16 and over it amounted to one severe case in about every 100 girls. Overall, these schools encountered one 'new' severe case in every 250 pupils aged 16 years and over. The condition is likely to be even more common than this study allows because of the stringent limits set here on inclusion of cases and the age-bands studied. It is concluded that severe anorexia nervosa is a common condition and is probably getting more common."} {"id": "PMID:1276564", "title": "Anorexia nervosa after the menopause.", "content": "A patient is described who developed the classical syndrome of anorexia nervosa at the age of 52. Her illness occurred in relation to the marriages of her daughters and showed an extreme preoccupation with her body shape and a determination to slim by diet, purging and vomiting, and the hiding of food to the extent of rendering herself too weak to cope with the demands of her life. It is suggested that anorexia nervosa, though predominantly a disease of onset in adolescence, may present at any age and should be considered in the differential diagnosis of anorexia in patients over the age of 50.", "contents": "Anorexia nervosa after the menopause. A patient is described who developed the classical syndrome of anorexia nervosa at the age of 52. Her illness occurred in relation to the marriages of her daughters and showed an extreme preoccupation with her body shape and a determination to slim by diet, purging and vomiting, and the hiding of food to the extent of rendering herself too weak to cope with the demands of her life. It is suggested that anorexia nervosa, though predominantly a disease of onset in adolescence, may present at any age and should be considered in the differential diagnosis of anorexia in patients over the age of 50."} {"id": "PMID:1276565", "title": "Anxiety and depression after infectious mononucleosis.", "content": "Thirty-six patients who had had infectious mononucleosis (IM) were followed up a year later and assessed by the Middlesex Hospital Questionnaire and by interview or (in five cases) by postal questionnaire. The results support the view that IM leads to depression in a considerable number of cases, but in this series only women were so affected.", "contents": "Anxiety and depression after infectious mononucleosis. Thirty-six patients who had had infectious mononucleosis (IM) were followed up a year later and assessed by the Middlesex Hospital Questionnaire and by interview or (in five cases) by postal questionnaire. The results support the view that IM leads to depression in a considerable number of cases, but in this series only women were so affected."} {"id": "PMID:1276566", "title": "Psychiatric aspects of narcolepsy.", "content": "Among twenty patients with narcolepsy intelligence was normal and no characteristic personality or psychopathology was found. A family history of psychiatric disorder was present in five and a past personal history in ten. Eight had a current psychiatric disorder and twelve either a current or past psychiatric disorder. Chronic sexual disorder was present in eleven. Arousal appeared to be the mechanism by which emotions precipitated symptoms. Ten patients were found to have had difficulties at work, in marriage or in social life.", "contents": "Psychiatric aspects of narcolepsy. Among twenty patients with narcolepsy intelligence was normal and no characteristic personality or psychopathology was found. A family history of psychiatric disorder was present in five and a past personal history in ten. Eight had a current psychiatric disorder and twelve either a current or past psychiatric disorder. Chronic sexual disorder was present in eleven. Arousal appeared to be the mechanism by which emotions precipitated symptoms. Ten patients were found to have had difficulties at work, in marriage or in social life."} {"id": "PMID:1276568", "title": "An intensive case-study of a therapeutic group.", "content": "A therapeutic group with eight members was studied, using psychometric tests, improvement ratings based on pre-treatment statements of patients' hopes, and of therapists' aims rated for achievement on the basis of post-treatment interviews, and two forms of repertory grid testing. The In-Group Grid yielded a number of measures relating to outcome and to aspects of the group process. Most patients improved by some criteria, and most measures of improvement intercorrelated positively but not, in most cases, highly. Few clear relations between process and outcome measures were demonstrated.", "contents": "An intensive case-study of a therapeutic group. A therapeutic group with eight members was studied, using psychometric tests, improvement ratings based on pre-treatment statements of patients' hopes, and of therapists' aims rated for achievement on the basis of post-treatment interviews, and two forms of repertory grid testing. The In-Group Grid yielded a number of measures relating to outcome and to aspects of the group process. Most patients improved by some criteria, and most measures of improvement intercorrelated positively but not, in most cases, highly. Few clear relations between process and outcome measures were demonstrated."} {"id": "PMID:1276569", "title": "Women senior registrars in psychiatry: background and career intentions.", "content": "An inquiry was made of all women senior registrats in general psychiatry who were known to be planning to remain in psychiatry in this country. Most were hoping to work full or maximum part-time, and all except one were aiming for a consultant appointment in general psychiatry or one of the specialties. Many anticipated difficulties in realizing their ambitions because of being tied to one particular area on account of their husbands' employment. A number of solutions to this problem are suggested.", "contents": "Women senior registrars in psychiatry: background and career intentions. An inquiry was made of all women senior registrats in general psychiatry who were known to be planning to remain in psychiatry in this country. Most were hoping to work full or maximum part-time, and all except one were aiming for a consultant appointment in general psychiatry or one of the specialties. Many anticipated difficulties in realizing their ambitions because of being tied to one particular area on account of their husbands' employment. A number of solutions to this problem are suggested."} {"id": "PMID:1276570", "title": "Women senior registrars in psychiatry: background and career intentions.", "content": "An inquiry was made of all women senior registrars in general psychiatry who were known to be planning to remain in psychiatry in this country. Most were hoping to work full or maximum part-time, and all except one were aiming for a consultant appointment in general psychiatry or one of the specialties. Many anticipated difficulties in realizing their ambitions because of being tied to one particular area on account of their husbands' employment. A number of solutions to this problem are suggested.", "contents": "Women senior registrars in psychiatry: background and career intentions. An inquiry was made of all women senior registrars in general psychiatry who were known to be planning to remain in psychiatry in this country. Most were hoping to work full or maximum part-time, and all except one were aiming for a consultant appointment in general psychiatry or one of the specialties. Many anticipated difficulties in realizing their ambitions because of being tied to one particular area on account of their husbands' employment. A number of solutions to this problem are suggested."} {"id": "PMID:1276572", "title": "The detection and significance of calcifications in the breast: a radiological and pathological study.", "content": "The radiological detection of calcification is compared using xeroradiography, non-screen film and a film-screen combination. The \"threshold\" values of the smallest detectable size of calcification, under simulated clinical conditions, are found to be approximately 100 mum for xeroradiography and 400 mum for both the film techniques in this study. The incidence of calcification seen on the preoperative mammograms of patients with carcinoma of the breast is 48-5 per cent. Further calcification revealed by histological examination raises the overall incidence of calcification in mammary carcinomas to 63 per cent. The incidence on preoperative mammograms in benign breast disease is 20 per cent. The radiological features of calcification occurring in malignant and benign breast lesions are recorded, and no definitive distinguishing features are established. The histological appearance of calcification in malignant and benign breast disease is discussed.", "contents": "The detection and significance of calcifications in the breast: a radiological and pathological study. The radiological detection of calcification is compared using xeroradiography, non-screen film and a film-screen combination. The \"threshold\" values of the smallest detectable size of calcification, under simulated clinical conditions, are found to be approximately 100 mum for xeroradiography and 400 mum for both the film techniques in this study. The incidence of calcification seen on the preoperative mammograms of patients with carcinoma of the breast is 48-5 per cent. Further calcification revealed by histological examination raises the overall incidence of calcification in mammary carcinomas to 63 per cent. The incidence on preoperative mammograms in benign breast disease is 20 per cent. The radiological features of calcification occurring in malignant and benign breast lesions are recorded, and no definitive distinguishing features are established. The histological appearance of calcification in malignant and benign breast disease is discussed."} {"id": "PMID:1276573", "title": "Congenital aganglionosis of the entire colon in neonates.", "content": "A report of six cases and their radiological diagnosis in neonates. Total colonic aganglionosis (TCA) is a variety of what is commonly known as long segment Hirschsprung's disease. This is not a rare condition, but is often unrecognized. It has a high mortality, frequently with a complicating enterocolitis. Aganglionosis of some part of the colon should be suspected in all babies who show obstructive plain film changes. In TCA the barium enema changes may easily be passed as unremarkable. However, free ileal reflux during the examination, with a transition point in the ileum, and retention of barium in the entire colon after the examination, are diagnostic.", "contents": "Congenital aganglionosis of the entire colon in neonates. A report of six cases and their radiological diagnosis in neonates. Total colonic aganglionosis (TCA) is a variety of what is commonly known as long segment Hirschsprung's disease. This is not a rare condition, but is often unrecognized. It has a high mortality, frequently with a complicating enterocolitis. Aganglionosis of some part of the colon should be suspected in all babies who show obstructive plain film changes. In TCA the barium enema changes may easily be passed as unremarkable. However, free ileal reflux during the examination, with a transition point in the ileum, and retention of barium in the entire colon after the examination, are diagnostic."} {"id": "PMID:1276574", "title": "The \"central lucency\" sign of lobar dysmorphism (pseudotumour of the kidney).", "content": "A proved case of pseudotumour of the kidney due to lobar dysmorphism showed a \"central lucency\" sign, differentiating this developmental variant from an enlarged column of Bertin. This sign is described in a further case.", "contents": "The \"central lucency\" sign of lobar dysmorphism (pseudotumour of the kidney). A proved case of pseudotumour of the kidney due to lobar dysmorphism showed a \"central lucency\" sign, differentiating this developmental variant from an enlarged column of Bertin. This sign is described in a further case."} {"id": "PMID:1276575", "title": "Factors involved in the detection of pulmonary emboli by labelling techniques.", "content": "Experiments were set up to assess quantitatively the problem of detecting, by scanning and gamma-camera, labelled pulmonary emboli in the presence of background radioactivity. In vitro, a relative concentration of radioactivity of 2:1 was required to detect a 1-1 cm diameter \"hot spot\". The results in vivo suggest that the level of radioactivity of a pulmonary embolus situated in the centre of the lung field should be at least six times that of the circulating blood.", "contents": "Factors involved in the detection of pulmonary emboli by labelling techniques. Experiments were set up to assess quantitatively the problem of detecting, by scanning and gamma-camera, labelled pulmonary emboli in the presence of background radioactivity. In vitro, a relative concentration of radioactivity of 2:1 was required to detect a 1-1 cm diameter \"hot spot\". The results in vivo suggest that the level of radioactivity of a pulmonary embolus situated in the centre of the lung field should be at least six times that of the circulating blood."} {"id": "PMID:1276576", "title": "Intestinal cell proliferation during fractionated abdominal irradiation.", "content": "In the mouse, at normal steady state of cell proliferation, the compensatory proliferative response to intestinal irradiation is such that when radiation exposures totalling 1,000 R are concentrated over the first few days of the week, summated proliferative activity for the entire week is near control levels. Symmetrically distributed exposures over a five-day treatment week (200 R daily, and especially 333 R on Monday, Wednesday and Friday) result in depressed levels of overall weekly proliferation. In these instances, the weekend break is particularly crucial. Similar results were obtained when the one-week measurement period was inserted between the third and fifth week of abdominal therapy, except in this instance, 200 R per day did not result in sub-control levels of proliferation, whereas 333 R on M, W and F, continued to do so. The intestine seems able to maintain its barrier epithelium for extended periods of diminished cell input, provided such is not too severe and that it seems from decreased cell production rate per crypt rather than from crypt attrition. A partial explanation for this relative tolerance is given by the finding that the vast majority of proliferative cells, even those irradiated and rendered permanently incapable of further division, succeed in migrating up the villus and hence help to maintain a barrier epithelium. In that sense, nearly all cell divisions become useful, even in the face of repeated exposures.", "contents": "Intestinal cell proliferation during fractionated abdominal irradiation. In the mouse, at normal steady state of cell proliferation, the compensatory proliferative response to intestinal irradiation is such that when radiation exposures totalling 1,000 R are concentrated over the first few days of the week, summated proliferative activity for the entire week is near control levels. Symmetrically distributed exposures over a five-day treatment week (200 R daily, and especially 333 R on Monday, Wednesday and Friday) result in depressed levels of overall weekly proliferation. In these instances, the weekend break is particularly crucial. Similar results were obtained when the one-week measurement period was inserted between the third and fifth week of abdominal therapy, except in this instance, 200 R per day did not result in sub-control levels of proliferation, whereas 333 R on M, W and F, continued to do so. The intestine seems able to maintain its barrier epithelium for extended periods of diminished cell input, provided such is not too severe and that it seems from decreased cell production rate per crypt rather than from crypt attrition. A partial explanation for this relative tolerance is given by the finding that the vast majority of proliferative cells, even those irradiated and rendered permanently incapable of further division, succeed in migrating up the villus and hence help to maintain a barrier epithelium. In that sense, nearly all cell divisions become useful, even in the face of repeated exposures."} {"id": "PMID:1276577", "title": "A practical approach to transverse-section gamma-ray imaging.", "content": "The object of transverse-section gamma-ray imaging is to display the concentration of radioactive material in a thin transverse slice of the body. The technique is essentially that of reconstructing a density distribution from its projections, and many methods have been developed to perform the reconstruction. This report describes the realization of three such methods, using a small digital computer PDP8 I, and their application to experimental and clinical data obtained from the Aberdeen Section Scanner: (1) simple back projection; (2) the convolution method of Bracewell and Riddle; (3) the linear integral transform method of Radon. The problems of sensitivity variation and attenuation are examined. An approximate attenuation correction procedure is described. The reconstruction method of Bracewell and Riddle was found convenient since then the data were manipulated in a manner where smoothing to reduce statistical noise and correction for absorption could both be readily incorporated.", "contents": "A practical approach to transverse-section gamma-ray imaging. The object of transverse-section gamma-ray imaging is to display the concentration of radioactive material in a thin transverse slice of the body. The technique is essentially that of reconstructing a density distribution from its projections, and many methods have been developed to perform the reconstruction. This report describes the realization of three such methods, using a small digital computer PDP8 I, and their application to experimental and clinical data obtained from the Aberdeen Section Scanner: (1) simple back projection; (2) the convolution method of Bracewell and Riddle; (3) the linear integral transform method of Radon. The problems of sensitivity variation and attenuation are examined. An approximate attenuation correction procedure is described. The reconstruction method of Bracewell and Riddle was found convenient since then the data were manipulated in a manner where smoothing to reduce statistical noise and correction for absorption could both be readily incorporated."} {"id": "PMID:1276578", "title": "A modified geometric factor approach to internal gamma ray dosimetry.", "content": "In internal gamma-ray dosimetry, the conventional geometric factor approach, where the \"effective absorption coefficient\" is taken as 0 or 0-028 cm-1, irrespective of source energy, leads to significant errors especially in the low energy region. An ettempt has been made in this paper to modify the approach to increase the accuracy of calculation and to extend its usefulness to low energies while retaining its inherent simplicity. The modification consists in replacing the effective absorption coefficient by the attenuation coefficients appropriate to the source energies and taking into account the effects due to multiple scattering by using point source build-up factor. The method has been applied for the particular case of dosimetry of a sphere. Comparison of the results obtained by this method with those got from Monte Carlo computations indicates excellent agreement at higher energies and a departure of around 15 per cent only at lower energies (as against a variation of 400 per cent when conventional geometric factor approach is used).", "contents": "A modified geometric factor approach to internal gamma ray dosimetry. In internal gamma-ray dosimetry, the conventional geometric factor approach, where the \"effective absorption coefficient\" is taken as 0 or 0-028 cm-1, irrespective of source energy, leads to significant errors especially in the low energy region. An ettempt has been made in this paper to modify the approach to increase the accuracy of calculation and to extend its usefulness to low energies while retaining its inherent simplicity. The modification consists in replacing the effective absorption coefficient by the attenuation coefficients appropriate to the source energies and taking into account the effects due to multiple scattering by using point source build-up factor. The method has been applied for the particular case of dosimetry of a sphere. Comparison of the results obtained by this method with those got from Monte Carlo computations indicates excellent agreement at higher energies and a departure of around 15 per cent only at lower energies (as against a variation of 400 per cent when conventional geometric factor approach is used)."} {"id": "PMID:1276579", "title": "Radiosensitization of C3H mouse mammary tumours using fractionated doses of x rays with the drug Ro-07-0582.", "content": "Three fractionated X-ray schedules were used, with and without the electron-affinic radiosensitizer of hypoxic cells, Ro-07-0582, to determine the local control of first-generation transplants of spontaneous mammary tumours in C3H mice. Three or five fractions were given in either four or nine days overall time. The results were compared with acute skin reactions in other mice caused by the same treatment schedules. For a given skin reaction, the local control of tumours varied widely, from good to bad, when different X-ray only schedules were used. All three schedules using Ro-07-0582 however yielded good results. It appears that the use of the hypoxic-cell radiosensitizer took the unreliability out of these short fractionated treatments.", "contents": "Radiosensitization of C3H mouse mammary tumours using fractionated doses of x rays with the drug Ro-07-0582. Three fractionated X-ray schedules were used, with and without the electron-affinic radiosensitizer of hypoxic cells, Ro-07-0582, to determine the local control of first-generation transplants of spontaneous mammary tumours in C3H mice. Three or five fractions were given in either four or nine days overall time. The results were compared with acute skin reactions in other mice caused by the same treatment schedules. For a given skin reaction, the local control of tumours varied widely, from good to bad, when different X-ray only schedules were used. All three schedules using Ro-07-0582 however yielded good results. It appears that the use of the hypoxic-cell radiosensitizer took the unreliability out of these short fractionated treatments."} {"id": "PMID:1276589", "title": "Late effects of x irradiation in patients treated for metropathia haemorrhagica.", "content": "We have previously reported on the causes of death among 2,068 patients treated with X irradiation for metropathia haemorrhagica at three Scottish radiotherapy centres between 1940 and 1960 (Doll and Smith, 1968). This cohort of women has now been followed up for a further seven years. 500 (24 per cent) women have now died, 78 (3-8 per cent) have emigrated and 25 (1-2 per cent) could not be traced. The numbers of deaths from different causes have been compared with the numbers expected in a population of similar age and sex exposed to the Scottish national mortality rates over the same period. An excess of deaths from leukaemia (seven observed, 2-3 expected) and of cancers of the heavily irradiated sites (59 observed, 40-1 expected) continues to be observed five or more years after treatment. There is no indication of any change in the excess death rate, due to cancers of sites in the radiation field, with time since treatment up to at least 20 years after the radiation exposure. Over the same period the number of deaths from cancer of the breast was below expectation (ten observed, 22-3 expected) and no increased mortality from coronary disease was seen (102 observed, 100-9 expected). The mean dose of radiation to the bone marrow has been determined for each woman ant it is estimated that the excess rate of leukaemia in the first 20 years after treatment is about 1-1 per million women per year per rad. This figure is in accord with the estimates derived from the survivors of the atomic bomb explosions in Hiroshima and Nagasaki and among patients with ankylosing spondylitis treated with X irradiation. However, the finding of no excess risk of leukemia among women treated with irradiation for cancer of the cervix (Hutchison, 1968) suggests that the simple assumption of a linear dose-response relationship for leukaemia is incorrect, at least when high doses of radiation are delivered to a small volume of marrow.", "contents": "Late effects of x irradiation in patients treated for metropathia haemorrhagica. We have previously reported on the causes of death among 2,068 patients treated with X irradiation for metropathia haemorrhagica at three Scottish radiotherapy centres between 1940 and 1960 (Doll and Smith, 1968). This cohort of women has now been followed up for a further seven years. 500 (24 per cent) women have now died, 78 (3-8 per cent) have emigrated and 25 (1-2 per cent) could not be traced. The numbers of deaths from different causes have been compared with the numbers expected in a population of similar age and sex exposed to the Scottish national mortality rates over the same period. An excess of deaths from leukaemia (seven observed, 2-3 expected) and of cancers of the heavily irradiated sites (59 observed, 40-1 expected) continues to be observed five or more years after treatment. There is no indication of any change in the excess death rate, due to cancers of sites in the radiation field, with time since treatment up to at least 20 years after the radiation exposure. Over the same period the number of deaths from cancer of the breast was below expectation (ten observed, 22-3 expected) and no increased mortality from coronary disease was seen (102 observed, 100-9 expected). The mean dose of radiation to the bone marrow has been determined for each woman ant it is estimated that the excess rate of leukaemia in the first 20 years after treatment is about 1-1 per million women per year per rad. This figure is in accord with the estimates derived from the survivors of the atomic bomb explosions in Hiroshima and Nagasaki and among patients with ankylosing spondylitis treated with X irradiation. However, the finding of no excess risk of leukemia among women treated with irradiation for cancer of the cervix (Hutchison, 1968) suggests that the simple assumption of a linear dose-response relationship for leukaemia is incorrect, at least when high doses of radiation are delivered to a small volume of marrow."} {"id": "PMID:1276590", "title": "Ultrasonic echo imaging of tissues: instrumentation.", "content": "The ultrasonic pulse-echo principle is capable of providing detailed information, of considerable potential diagnostic value, on the structure of soft tissues in relation to pathology, but the present generation of ultrasonic scanners does not fully exploit this possibility. The paper discusses the principal measures necessary to achieve tissue structure visualization and quantitative characterization and describes a clinically functioning system that has been built for this purpose with particular relation to cancer diagnosis. Examples of the application of the system are given in this and an accompanying paper.", "contents": "Ultrasonic echo imaging of tissues: instrumentation. The ultrasonic pulse-echo principle is capable of providing detailed information, of considerable potential diagnostic value, on the structure of soft tissues in relation to pathology, but the present generation of ultrasonic scanners does not fully exploit this possibility. The paper discusses the principal measures necessary to achieve tissue structure visualization and quantitative characterization and describes a clinically functioning system that has been built for this purpose with particular relation to cancer diagnosis. Examples of the application of the system are given in this and an accompanying paper."} {"id": "PMID:1276591", "title": "A clinical evaluation of grey-scale ultrasonography.", "content": "Recent technical improvements in grey-scale ultrasound imaging have resulted in the visualization of the internal consistency of soft tissues. This permits the diagnosis of diffuse pathology and detection of small space-occupying lesions. The new technique can be used with advantage in the currently accepted obstetrical applications for ultrasound imaging as well as for new non-obstetrical applications. The method has been found to be a most informative, non-intrusive means for investigating hepatobiliary disease and for the differential diagnosis of chronic splenomegaly.", "contents": "A clinical evaluation of grey-scale ultrasonography. Recent technical improvements in grey-scale ultrasound imaging have resulted in the visualization of the internal consistency of soft tissues. This permits the diagnosis of diffuse pathology and detection of small space-occupying lesions. The new technique can be used with advantage in the currently accepted obstetrical applications for ultrasound imaging as well as for new non-obstetrical applications. The method has been found to be a most informative, non-intrusive means for investigating hepatobiliary disease and for the differential diagnosis of chronic splenomegaly."} {"id": "PMID:1276592", "title": "Radiation exposure to the patient in xeroradiography.", "content": "The paper presents measurements of the radiation exposure required in xeroradiography of the breast and of the extremities. The nature of the radiation hazard and the most appropriate quantity by which to assess it are discussed, and it is shown that for a number of radiological procedures xeroradiographs can be taken for about the same radiation exposure to the patient as that required by conventional film techniques.", "contents": "Radiation exposure to the patient in xeroradiography. The paper presents measurements of the radiation exposure required in xeroradiography of the breast and of the extremities. The nature of the radiation hazard and the most appropriate quantity by which to assess it are discussed, and it is shown that for a number of radiological procedures xeroradiographs can be taken for about the same radiation exposure to the patient as that required by conventional film techniques."} {"id": "PMID:1276593", "title": "The measurement of the performance of the display system of radioisotope imaging device: the multi-element band display.", "content": "An assessment has been made of the performance of the type of display system in which each display signal intensity, i.e. grey shade or colour, represents a range of count densities or counting rates. In the particular commercially available system used in this investigation eight different grey shades are used to display the image, a range of count densities beingallocated to each grey shade. It is shown experimentally that changes in the distribution of radioisotope can fail to be detected solely due to the manner in which the display is used, viz. The way in which the count density is allocated to the available grey shades. Also, it is shown experimentally that the best display performance can be achieved by using one in which the range of count densities represented by each grey shade is less than three standard deviations of the mean background [corrected] count density.", "contents": "The measurement of the performance of the display system of radioisotope imaging device: the multi-element band display. An assessment has been made of the performance of the type of display system in which each display signal intensity, i.e. grey shade or colour, represents a range of count densities or counting rates. In the particular commercially available system used in this investigation eight different grey shades are used to display the image, a range of count densities beingallocated to each grey shade. It is shown experimentally that changes in the distribution of radioisotope can fail to be detected solely due to the manner in which the display is used, viz. The way in which the count density is allocated to the available grey shades. Also, it is shown experimentally that the best display performance can be achieved by using one in which the range of count densities represented by each grey shade is less than three standard deviations of the mean background [corrected] count density."} {"id": "PMID:1276623", "title": "Gas myelography in the investigation of occult spinal dysraphism.", "content": "In patients presenting with suspected spinal dysraphism of the occult type, particularly children, cisternal gas myelography is coming to be accepted as the radiological investigation of choice. The technique of the examination as performed on 40 such patients is described in detail. There have been no complications. Twenty-five patients showed abnormalities of the cord together with low termination and abnormal fixation of the conus. The visualization was excellent in terms both of reliability and detail. The reasons for the difficulties in demonstrating these lesions using positive contrast and for preferring gas myelography are discussed.", "contents": "Gas myelography in the investigation of occult spinal dysraphism. In patients presenting with suspected spinal dysraphism of the occult type, particularly children, cisternal gas myelography is coming to be accepted as the radiological investigation of choice. The technique of the examination as performed on 40 such patients is described in detail. There have been no complications. Twenty-five patients showed abnormalities of the cord together with low termination and abnormal fixation of the conus. The visualization was excellent in terms both of reliability and detail. The reasons for the difficulties in demonstrating these lesions using positive contrast and for preferring gas myelography are discussed."} {"id": "PMID:1276624", "title": "Xerotomography of pulmonary lesions.", "content": "Xerography in combination with tomography is a useful modality in evaluating pulmonary lesions. Comparison is made between this technique and conventional film tomography. Xerotomography is felt to be preferable although it requires considerably higher radiation exposure to the patient.", "contents": "Xerotomography of pulmonary lesions. Xerography in combination with tomography is a useful modality in evaluating pulmonary lesions. Comparison is made between this technique and conventional film tomography. Xerotomography is felt to be preferable although it requires considerably higher radiation exposure to the patient."} {"id": "PMID:1276625", "title": "Differential diagnosis of chronic splenomegaly by grey-scale ultrasonography: Clinical observations and digital A-scan analysis.", "content": "Hitherto, ultrasound examination of the spleen has been limited to the determination of size and position. Grey-scale ultrasonography involves enhanced signal-to-noise ratio so that the soft-tissue texture is displayed, and this permits the recognition of diffusely abnormal consistency. This facility was used to predict lymphomatous involvement of the spleen in patients coming to laparotomy in whom an accuracy of 77-8 per cent was achieved. Three types of splenic consistency are described in a series of 60 patients presenting with chronic splenomegaly: Very low-level echoes emanate from malignantly involved spleens. Medium-level echoes are found in various benign conditions and high-level echoes occur in various chronic inflammatory conditions. These differences were confirmed and quantitated by computerized A-scan analysis.", "contents": "Differential diagnosis of chronic splenomegaly by grey-scale ultrasonography: Clinical observations and digital A-scan analysis. Hitherto, ultrasound examination of the spleen has been limited to the determination of size and position. Grey-scale ultrasonography involves enhanced signal-to-noise ratio so that the soft-tissue texture is displayed, and this permits the recognition of diffusely abnormal consistency. This facility was used to predict lymphomatous involvement of the spleen in patients coming to laparotomy in whom an accuracy of 77-8 per cent was achieved. Three types of splenic consistency are described in a series of 60 patients presenting with chronic splenomegaly: Very low-level echoes emanate from malignantly involved spleens. Medium-level echoes are found in various benign conditions and high-level echoes occur in various chronic inflammatory conditions. These differences were confirmed and quantitated by computerized A-scan analysis."} {"id": "PMID:1276626", "title": "Report on treatment of cancer of the ovary.", "content": "A malignant ovarian tumour has been diagnosed in 373 patients referred to the R.R.T.I. from January 1966 to Jun 1972. Serious ovarian carcinoma was the commonest type and occurred in 254 patients. The results in these patients are studied in detail after staging according to F.I.G.O. recommendations. Following surgery and postoperative radiotherapy, chemotherapy was started immediately in all patients with progressive disease and after randomization also in 50 per cent of the others. The three-year survival rate in Stage II patients tended to be more favourable following irridation ofthe pelvis and lumboaortic nodes (55 per cent ) than following radiotherapy restricted to the pelvic area (40 per cent). The dose should be 5-6 krad. The five-year survival was 68 per cent for Stage I, 26 per cent for Stage II and nearly zero for Stages III and IV, as well as for patients referred for treatment of a recurrence. In spite of whole-abdomen irradiation 50 per cent of the patients in the latter three groups were deceased within eight months; therefore chemotherapy should be preferred. The main problem in ovarian cancer is late diagnosis. Evaluation of results is difficult because numerous variable factors concerning pathology and treatment make it necessary to sub-divide the patients into groups too small for statistically reliable conclusions. Each treatment factor should be studied by a group of hospitals.", "contents": "Report on treatment of cancer of the ovary. A malignant ovarian tumour has been diagnosed in 373 patients referred to the R.R.T.I. from January 1966 to Jun 1972. Serious ovarian carcinoma was the commonest type and occurred in 254 patients. The results in these patients are studied in detail after staging according to F.I.G.O. recommendations. Following surgery and postoperative radiotherapy, chemotherapy was started immediately in all patients with progressive disease and after randomization also in 50 per cent of the others. The three-year survival rate in Stage II patients tended to be more favourable following irridation ofthe pelvis and lumboaortic nodes (55 per cent ) than following radiotherapy restricted to the pelvic area (40 per cent). The dose should be 5-6 krad. The five-year survival was 68 per cent for Stage I, 26 per cent for Stage II and nearly zero for Stages III and IV, as well as for patients referred for treatment of a recurrence. In spite of whole-abdomen irradiation 50 per cent of the patients in the latter three groups were deceased within eight months; therefore chemotherapy should be preferred. The main problem in ovarian cancer is late diagnosis. Evaluation of results is difficult because numerous variable factors concerning pathology and treatment make it necessary to sub-divide the patients into groups too small for statistically reliable conclusions. Each treatment factor should be studied by a group of hospitals."} {"id": "PMID:1276627", "title": "Calculation by computer of dose distributions for superficial gold-198 implants and the derivation of optimized distribution rules.", "content": "A computer program has been written which provides two-dimensional visualization of the radiation dose distributions in the treatment surfaces aroung single-plane gold seed implants. The program was modified in order to investigate the uniformity of dose resulting from various patterns of seed arrangements, and, for a number of sizes of circular implants, practical loading schemes to produce minimum dose variations have been tabulated. Comparisons are made between dose distributions obtained from application of the derived data and those arising from application of the Paterson-Parker rules.", "contents": "Calculation by computer of dose distributions for superficial gold-198 implants and the derivation of optimized distribution rules. A computer program has been written which provides two-dimensional visualization of the radiation dose distributions in the treatment surfaces aroung single-plane gold seed implants. The program was modified in order to investigate the uniformity of dose resulting from various patterns of seed arrangements, and, for a number of sizes of circular implants, practical loading schemes to produce minimum dose variations have been tabulated. Comparisons are made between dose distributions obtained from application of the derived data and those arising from application of the Paterson-Parker rules."} {"id": "PMID:1276656", "title": "Treatment of thyroid cancer in 293 patients.", "content": "Two hundred and ninety-three patients with thyroid cancer were treated at The Royal Marsden Hospital, London, between 1931 and 1963. Thirty-six per cent of the tumours were papillary, 21 per cent follicular, 1 per cent medullary and 42 per cent anaplastic. Surgery combined with radiotherapy formed the commonest treatment regime. Thirty-six per cent of the patients with papillary carcinoma survived for 20 years, 20 per cent with follicular tumour and 4 per cent with anaplastic carcinoma. The present series indicates that treatment influences the survival time, confirms the prognostic value of histology and age and shows that papillary node metastases do not prejudice survival.", "contents": "Treatment of thyroid cancer in 293 patients. Two hundred and ninety-three patients with thyroid cancer were treated at The Royal Marsden Hospital, London, between 1931 and 1963. Thirty-six per cent of the tumours were papillary, 21 per cent follicular, 1 per cent medullary and 42 per cent anaplastic. Surgery combined with radiotherapy formed the commonest treatment regime. Thirty-six per cent of the patients with papillary carcinoma survived for 20 years, 20 per cent with follicular tumour and 4 per cent with anaplastic carcinoma. The present series indicates that treatment influences the survival time, confirms the prognostic value of histology and age and shows that papillary node metastases do not prejudice survival."} {"id": "PMID:1276657", "title": "Total three-stage oesophagectomy for cancer of the oesophagus.", "content": "The technique of total three-stage oesophagectomy is described fully. Points of detail in the procedure of the abdominal, thoracic and cervical phases are emphasized. A brief note is made regarding the management of the respiratory situation at the end of the operation.", "contents": "Total three-stage oesophagectomy for cancer of the oesophagus. The technique of total three-stage oesophagectomy is described fully. Points of detail in the procedure of the abdominal, thoracic and cervical phases are emphasized. A brief note is made regarding the management of the respiratory situation at the end of the operation."} {"id": "PMID:1276658", "title": "Liver abnormalities and gallstones: a prospective combined clinical, histological and surgical study.", "content": "In a prospective study of 57 patients coming to elective cholecystectomy for gallstone disease, clinical, biochemical and immunological features have been correlated with the histological changes in core biopsies of the liver obtained at surgery. Only 13 liver biopsies were normal. Ten biopsies showed changes of acute duct obstruction, 16 showed minimal portal tract abnormalities and 10 showed moderate portal tract inflammation and scarring. Histological changes were more marked in male patients. Clinical and biochemical investigations were not useful in predicting histological appearance, apart from cases with jaundice at the time of operation where changes of acute duct obstruction were usually, but not invariably, seen. Atuo-antibodies were present in 50 per cent of cases tested and all persisted for at least 6 months after operation. They were commoner in patients with more marked histological changes. Operative cholangiography was of little use in predicting histological change. These findings suggest that the possibility of gallstones should be considered in the interpretation of any abnormal liver biopsy irrespective of clinical symptoms or biochemical investigations.", "contents": "Liver abnormalities and gallstones: a prospective combined clinical, histological and surgical study. In a prospective study of 57 patients coming to elective cholecystectomy for gallstone disease, clinical, biochemical and immunological features have been correlated with the histological changes in core biopsies of the liver obtained at surgery. Only 13 liver biopsies were normal. Ten biopsies showed changes of acute duct obstruction, 16 showed minimal portal tract abnormalities and 10 showed moderate portal tract inflammation and scarring. Histological changes were more marked in male patients. Clinical and biochemical investigations were not useful in predicting histological appearance, apart from cases with jaundice at the time of operation where changes of acute duct obstruction were usually, but not invariably, seen. Atuo-antibodies were present in 50 per cent of cases tested and all persisted for at least 6 months after operation. They were commoner in patients with more marked histological changes. Operative cholangiography was of little use in predicting histological change. These findings suggest that the possibility of gallstones should be considered in the interpretation of any abnormal liver biopsy irrespective of clinical symptoms or biochemical investigations."} {"id": "PMID:1276659", "title": "Brucellosis of the spine.", "content": "Three cases of spinal brucellosis are presented, demonstrating involvement of the cervical, thoracic and lumbar regions respectively, and the management is discussed. Particular reference is made to the problems of establishing the diagnosis, and also the differentiation of this condition from tuberculosis of the spine.", "contents": "Brucellosis of the spine. Three cases of spinal brucellosis are presented, demonstrating involvement of the cervical, thoracic and lumbar regions respectively, and the management is discussed. Particular reference is made to the problems of establishing the diagnosis, and also the differentiation of this condition from tuberculosis of the spine."} {"id": "PMID:1276660", "title": "Fluid-filled intestinal obstruction.", "content": "Three cases of intestinal obstruction are described in which the diagnosis was delayed because of the absence of gas in the bowel. The obstructed bowel was entirely fluid-filled and so abdominal distension was not marked, peristaltic sounds were not accentuated and the abdominal X-rays did not show air-fluid levels.", "contents": "Fluid-filled intestinal obstruction. Three cases of intestinal obstruction are described in which the diagnosis was delayed because of the absence of gas in the bowel. The obstructed bowel was entirely fluid-filled and so abdominal distension was not marked, peristaltic sounds were not accentuated and the abdominal X-rays did not show air-fluid levels."} {"id": "PMID:1276661", "title": "The effects of Corynebacterium parvum and surgery on the Lewis lung carcinoma and its metastases.", "content": "The effects of Corynebacterium parvum on the mouse primary Lewis lung carcinoma and its metastases were studied. C. parvum was given at the same time as subcutaneous inoculation of tumour or in combination with surgical excision of the primary after 10 days' growth. When intravenous C. parvum was given at the same time as tumour there was a reduction in the primary tumour growth rate. There was a similar reduction in growth if the drug was given intravenously 7 days after tumour inoculation. Intraperitoneal and subcutaneous administration of C. parvum had no effect on the primary tumour. The number of pulmonary metastases were significantly reduced after intravenous or intraperitoneal C. parvum given at the same time as tumour. When C. parvum and surgery were combined and C. parvum was given not more than 2 days before operation there was only a slight reduction in metastases, but when the injection was given intravenously or intraperitoneally 3-4 days before operation the number of metastases was significantly reduced. Subcutaneous administration of C. parvum had little effect on metastases. There was no difference in the number of metastases in C. parvum-treated mice were killed after 21 or 28 days. C. parvum given on the same day as surgery was more effective if tumour excision was performed before day 10 when the metastases were less well established. It was concluded that in well-defined conditions C. parvum is effective against metastases of the Lewis lung carcinoma.", "contents": "The effects of Corynebacterium parvum and surgery on the Lewis lung carcinoma and its metastases. The effects of Corynebacterium parvum on the mouse primary Lewis lung carcinoma and its metastases were studied. C. parvum was given at the same time as subcutaneous inoculation of tumour or in combination with surgical excision of the primary after 10 days' growth. When intravenous C. parvum was given at the same time as tumour there was a reduction in the primary tumour growth rate. There was a similar reduction in growth if the drug was given intravenously 7 days after tumour inoculation. Intraperitoneal and subcutaneous administration of C. parvum had no effect on the primary tumour. The number of pulmonary metastases were significantly reduced after intravenous or intraperitoneal C. parvum given at the same time as tumour. When C. parvum and surgery were combined and C. parvum was given not more than 2 days before operation there was only a slight reduction in metastases, but when the injection was given intravenously or intraperitoneally 3-4 days before operation the number of metastases was significantly reduced. Subcutaneous administration of C. parvum had little effect on metastases. There was no difference in the number of metastases in C. parvum-treated mice were killed after 21 or 28 days. C. parvum given on the same day as surgery was more effective if tumour excision was performed before day 10 when the metastases were less well established. It was concluded that in well-defined conditions C. parvum is effective against metastases of the Lewis lung carcinoma."} {"id": "PMID:1276662", "title": "Colitis and diarrhoea: a problem with antibiotic therapy.", "content": "During a 19-month study the incidence of diarrhoea and colitis was estimated in 1158 orthopaedic inpatients admitted to the Guy's group of hospitals. The highest incidence of diarrhoea followed the use of lincomycin (22.2 per cent), ampicillin with cloxacillin (17.2 per cent), clindamycin (15.3 per cent) and combined therapy with cloxacillin and tetracycline (12.5 per cent). There were 3 documented cases of colitis; 2 followed lincomycin and 1 clindamycin. The incidence and relationship of antibiotic-related diarrhoea and colitis to possible aetiological factors are discussed. In orthopaedic inpatients, in whom lincomycin and clindamycin are often the antibiotics of choice, their continued use appears to be fully justified by the low incidence of colitis. However, if a patient receiving treatment with either of these antibiotics does develop diarrhoea, the antibiotic should be discontinued immediately, to reduce the risk of subsequent colitis.", "contents": "Colitis and diarrhoea: a problem with antibiotic therapy. During a 19-month study the incidence of diarrhoea and colitis was estimated in 1158 orthopaedic inpatients admitted to the Guy's group of hospitals. The highest incidence of diarrhoea followed the use of lincomycin (22.2 per cent), ampicillin with cloxacillin (17.2 per cent), clindamycin (15.3 per cent) and combined therapy with cloxacillin and tetracycline (12.5 per cent). There were 3 documented cases of colitis; 2 followed lincomycin and 1 clindamycin. The incidence and relationship of antibiotic-related diarrhoea and colitis to possible aetiological factors are discussed. In orthopaedic inpatients, in whom lincomycin and clindamycin are often the antibiotics of choice, their continued use appears to be fully justified by the low incidence of colitis. However, if a patient receiving treatment with either of these antibiotics does develop diarrhoea, the antibiotic should be discontinued immediately, to reduce the risk of subsequent colitis."} {"id": "PMID:1276663", "title": "Fatal pseudomembranous enterocolitis following clindamycin therapy.", "content": "A fatal case of pseudomembranous enterocolitis following oral and parenteral clindamycin therapy is presented. Interesting features in this case are involvement of the small bowel and complete sparing of the large bowel distal to a defunctioning transverse colostomy. The significance of the absence of disease in the defunctioned bowel is discussed in terms of aetiology and diagnosis of pseudomembranous enterocolitis.", "contents": "Fatal pseudomembranous enterocolitis following clindamycin therapy. A fatal case of pseudomembranous enterocolitis following oral and parenteral clindamycin therapy is presented. Interesting features in this case are involvement of the small bowel and complete sparing of the large bowel distal to a defunctioning transverse colostomy. The significance of the absence of disease in the defunctioned bowel is discussed in terms of aetiology and diagnosis of pseudomembranous enterocolitis."} {"id": "PMID:1276664", "title": "Distal colomyotomy: follow-up of 37 cases.", "content": "The 3-7-year follow-up results of 37 patients undergoing the operation of distal colomyotomy are reported. Twenty-five underwent surgery for uncomplicated diverticular disease; there was no mortality but 40 per cent of patients had recurrent symptoms. Twelve patients underwent surgery for complicated diverticular disease, with an operative mortality of 16-6 per cent and a recurrent symptom rate of 37-5 per cent.", "contents": "Distal colomyotomy: follow-up of 37 cases. The 3-7-year follow-up results of 37 patients undergoing the operation of distal colomyotomy are reported. Twenty-five underwent surgery for uncomplicated diverticular disease; there was no mortality but 40 per cent of patients had recurrent symptoms. Twelve patients underwent surgery for complicated diverticular disease, with an operative mortality of 16-6 per cent and a recurrent symptom rate of 37-5 per cent."} {"id": "PMID:1276665", "title": "Typhoid ileal perforations: why such mortalities?", "content": "The average mortality of 25 per cent in typhoid perforations of the ileum treated operatively could be reduced, because only half of the cases die of the lethal complications of myocarditis and toxaemia. The results of the present study show important differences between the preoperative fluid and electrolyte therapy of survivors and non-survivors as well as differences in the urinary output per hour. The perforation-operation interval as well as duration of the illness also have prognostic significance. The problem of enteric fever must ultimately be solved by preventive measures, but the results of this review indicate that attention to these factors could halve the present mortality.", "contents": "Typhoid ileal perforations: why such mortalities? The average mortality of 25 per cent in typhoid perforations of the ileum treated operatively could be reduced, because only half of the cases die of the lethal complications of myocarditis and toxaemia. The results of the present study show important differences between the preoperative fluid and electrolyte therapy of survivors and non-survivors as well as differences in the urinary output per hour. The perforation-operation interval as well as duration of the illness also have prognostic significance. The problem of enteric fever must ultimately be solved by preventive measures, but the results of this review indicate that attention to these factors could halve the present mortality."} {"id": "PMID:1276666", "title": "A retrospective analysis of the accuracy of immediate frozen section diagnosis in surgical pathology.", "content": "An evaluation of the accuracy of 3556 frozen section diagnoses over a 10-year period has been carried out. The overall accuracy rate was 97.4 per cent, with umimportant discrepancies present in a further 1.8 per cent. In only 28 cases (0.8 per cent) was a false negative or positive diagnosis of malignancy made. Of these, 4 patients underwent an unnecessary radical operation, while in 9 patients further surgery had to be carried out at a later date. The essential accuracy of the frozen section technique is confirmed.", "contents": "A retrospective analysis of the accuracy of immediate frozen section diagnosis in surgical pathology. An evaluation of the accuracy of 3556 frozen section diagnoses over a 10-year period has been carried out. The overall accuracy rate was 97.4 per cent, with umimportant discrepancies present in a further 1.8 per cent. In only 28 cases (0.8 per cent) was a false negative or positive diagnosis of malignancy made. Of these, 4 patients underwent an unnecessary radical operation, while in 9 patients further surgery had to be carried out at a later date. The essential accuracy of the frozen section technique is confirmed."} {"id": "PMID:1276667", "title": "Intermittent non-sterile self-catheterization.", "content": "Fourteen patients suffering from voiding disorders of various aetiologies were taught the art of intermittent self-catheterization. The rationale of this form of treatment is discussed and it is suggested that this regime may play a useful role in the management of patients who are not amenable to surgery or other forms of treatment.", "contents": "Intermittent non-sterile self-catheterization. Fourteen patients suffering from voiding disorders of various aetiologies were taught the art of intermittent self-catheterization. The rationale of this form of treatment is discussed and it is suggested that this regime may play a useful role in the management of patients who are not amenable to surgery or other forms of treatment."} {"id": "PMID:1276668", "title": "Cancer prognosis predicted by preoperative lymphocyte responsiveness in vitro.", "content": "The prognosis in cancer patients was studied in relation to their preoperative cell-mediated immune status. Thirty patients with various types of operable cancer were studied. Transformation of the lymphocytes in response to phytohaemagglutinin (PHA) in vitro was measured preoperatively. All the patients were followed up for 3 years. Those with normal preoperative lymphocyte responsiveness had a far better prognosis than those in whom this test was subnormal.", "contents": "Cancer prognosis predicted by preoperative lymphocyte responsiveness in vitro. The prognosis in cancer patients was studied in relation to their preoperative cell-mediated immune status. Thirty patients with various types of operable cancer were studied. Transformation of the lymphocytes in response to phytohaemagglutinin (PHA) in vitro was measured preoperatively. All the patients were followed up for 3 years. Those with normal preoperative lymphocyte responsiveness had a far better prognosis than those in whom this test was subnormal."} {"id": "PMID:1276669", "title": "Assessment of portasystemic shunt patency by estimation of D-xylose excretion.", "content": "The D-xylose excretion test appears to be a useful method of monitoring shunt patency after a portasystemic venous anastomsis for portal hypertension. A 5-hour urinary excretion greater than 6 g appears an acceptable indicator that the shunt is patent. A second criterion of patency is an increase of 4 g or more over the result of preoperative tests. If the excretion rate falls in the postoperative period or remains less than 4-2 g/5 h, the anastomosis may be assumed to be occluded.", "contents": "Assessment of portasystemic shunt patency by estimation of D-xylose excretion. The D-xylose excretion test appears to be a useful method of monitoring shunt patency after a portasystemic venous anastomsis for portal hypertension. A 5-hour urinary excretion greater than 6 g appears an acceptable indicator that the shunt is patent. A second criterion of patency is an increase of 4 g or more over the result of preoperative tests. If the excretion rate falls in the postoperative period or remains less than 4-2 g/5 h, the anastomosis may be assumed to be occluded."} {"id": "PMID:1276670", "title": "A comparison of operative cholangiographic technique.", "content": "The accuracy and postoperative morbidity of cannulation of the cystic duct in routine operative cholangiography were compared with those of needle puncture of the common bile duct. The results are comparable and a case is made for the simpler procedure of needle puncture of the common duct.", "contents": "A comparison of operative cholangiographic technique. The accuracy and postoperative morbidity of cannulation of the cystic duct in routine operative cholangiography were compared with those of needle puncture of the common bile duct. The results are comparable and a case is made for the simpler procedure of needle puncture of the common duct."} {"id": "PMID:1276671", "title": "An experimental evaluation of the types of material used for bile duct drainage tubes.", "content": "A comparison has been carried out of the properties of latex, silicone, red rubber and polyvinyl chloride (PVC) T tubes draining the common bile duct in dogs. The tubes remained in the animals for 15-98 days. Bile cultures, liver function tests, cholangiograms and the histology of the common bile ducts were studied, and the changes in the physical properties of tubes implanted in the experimental animals, and of those after 1 month's incubation in human bile, were assessed. The elasticity of the tubes was also measured and the tissue reaction around them observed. Finally, the tissue reaction following implantation in mice of tubes which had been incubated in human bile for 1 month was investigated, and compared with that when new tubes were used. Polyvinyl chloride tubes caused the least reaction in both the common bile duct and the peritoneal cavity. However, the lack of tissue tract formation around them, owing to their inertness, and their rapid development of rigidity make them unsuitable for use in biliary surgery. Red rubber tubes were found to be the most irritant. While silicone tubes proved to have desirable physical properties compared with latex tubes, they did, however, disintegrate easily with improper handling on suturing and were slow to produce a satisfactory tract, the latter fact suggesting that they would be unsuitable for short term biliary drainage. It appears that the latex tube is the tube of choice for drainage periods of up to 3 months, while silicone tubes are preferable when intubation for longer periods is necessary. Red rubber tubes may be the alternative for routine short term drainage if a latex tube is not available.", "contents": "An experimental evaluation of the types of material used for bile duct drainage tubes. A comparison has been carried out of the properties of latex, silicone, red rubber and polyvinyl chloride (PVC) T tubes draining the common bile duct in dogs. The tubes remained in the animals for 15-98 days. Bile cultures, liver function tests, cholangiograms and the histology of the common bile ducts were studied, and the changes in the physical properties of tubes implanted in the experimental animals, and of those after 1 month's incubation in human bile, were assessed. The elasticity of the tubes was also measured and the tissue reaction around them observed. Finally, the tissue reaction following implantation in mice of tubes which had been incubated in human bile for 1 month was investigated, and compared with that when new tubes were used. Polyvinyl chloride tubes caused the least reaction in both the common bile duct and the peritoneal cavity. However, the lack of tissue tract formation around them, owing to their inertness, and their rapid development of rigidity make them unsuitable for use in biliary surgery. Red rubber tubes were found to be the most irritant. While silicone tubes proved to have desirable physical properties compared with latex tubes, they did, however, disintegrate easily with improper handling on suturing and were slow to produce a satisfactory tract, the latter fact suggesting that they would be unsuitable for short term biliary drainage. It appears that the latex tube is the tube of choice for drainage periods of up to 3 months, while silicone tubes are preferable when intubation for longer periods is necessary. Red rubber tubes may be the alternative for routine short term drainage if a latex tube is not available."} {"id": "PMID:1276672", "title": "Spontaneous perforation of the common hepatic duct.", "content": "A case of spontaneous calculous perforation of the common hepatic duct is presented. The late result of duct repair, that of stricture formation, is illustrated.", "contents": "Spontaneous perforation of the common hepatic duct. A case of spontaneous calculous perforation of the common hepatic duct is presented. The late result of duct repair, that of stricture formation, is illustrated."} {"id": "PMID:1276673", "title": "Double intussusception of the small bowel through a patent vitello-intestinal duct.", "content": "A case of double intussusception through a patent vitello-intestinal duct is reported. The rarity of this condition is the reason for this short report.", "contents": "Double intussusception of the small bowel through a patent vitello-intestinal duct. A case of double intussusception through a patent vitello-intestinal duct is reported. The rarity of this condition is the reason for this short report."} {"id": "PMID:1276674", "title": "Bilharzial polyposis of the rectum and sigmoid colon.", "content": "The case is reported of a 10-year-old boy who had severe diarrhoea with blood and muscus for 1 year which was found to be due to bilharzial polyposis of the rectum and sigmoid colon. He was treated first with antibilharzial drugs. Later, because of multiple polyps and secondary infection, local surgical resection was performed.", "contents": "Bilharzial polyposis of the rectum and sigmoid colon. The case is reported of a 10-year-old boy who had severe diarrhoea with blood and muscus for 1 year which was found to be due to bilharzial polyposis of the rectum and sigmoid colon. He was treated first with antibilharzial drugs. Later, because of multiple polyps and secondary infection, local surgical resection was performed."} {"id": "PMID:1276675", "title": "An instrumental method of performing Lord's procedure for haemorrhoids.", "content": "An instrument has been designed for carrying out Lord's procedure in the treatment of haemorrhoids. This permits standardization of the procedure with less likelihood of mucosal trauma. The inflatable dilator is covered by a disposable plastic cover. The efficacy of the instrument has been established.", "contents": "An instrumental method of performing Lord's procedure for haemorrhoids. An instrument has been designed for carrying out Lord's procedure in the treatment of haemorrhoids. This permits standardization of the procedure with less likelihood of mucosal trauma. The inflatable dilator is covered by a disposable plastic cover. The efficacy of the instrument has been established."} {"id": "PMID:1276676", "title": "Outpatient treatment of haemorrhoids by cryotherapy.", "content": "The treatment of haemorrhoids by cryosurgery is fairly new. One hundred cases have been analysed and the results presented as a preliminary report. Although the maximum follow-up is only 18 months, so far the results have been encouraging, and should they be maintained this method of outpatient haemorrhoidectomy could dramatically alter the management of this condition.", "contents": "Outpatient treatment of haemorrhoids by cryotherapy. The treatment of haemorrhoids by cryosurgery is fairly new. One hundred cases have been analysed and the results presented as a preliminary report. Although the maximum follow-up is only 18 months, so far the results have been encouraging, and should they be maintained this method of outpatient haemorrhoidectomy could dramatically alter the management of this condition."} {"id": "PMID:1276677", "title": "Congenital absence of the vas deferns.", "content": "A case is presented of congenital absence of the left vas deferens, kidney and ureter, and the literature relating to this anomaly is reviewed.", "contents": "Congenital absence of the vas deferns. A case is presented of congenital absence of the left vas deferens, kidney and ureter, and the literature relating to this anomaly is reviewed."} {"id": "PMID:1276678", "title": "Factors determining the rate of disappearance of sperm from the ejaculate after vasectomy.", "content": "The relative importance of age and frequency of coitus in determining the time needed for the semen count to become negative after vasectomy was studied in a group of 831 men. Irrespective of the frequency of coitus, there was a highly significant positive correlation between a patient's age and the time taken to become aspermic. This has implications for general practice: the older patient should be warned that he will take longer than a younger man to become sterile.", "contents": "Factors determining the rate of disappearance of sperm from the ejaculate after vasectomy. The relative importance of age and frequency of coitus in determining the time needed for the semen count to become negative after vasectomy was studied in a group of 831 men. Irrespective of the frequency of coitus, there was a highly significant positive correlation between a patient's age and the time taken to become aspermic. This has implications for general practice: the older patient should be warned that he will take longer than a younger man to become sterile."} {"id": "PMID:1276679", "title": "Fournier's gangrene: a report of 5 cases.", "content": "A report of 5 cases of infective gangrene of the genitalia and adjacent tissues occuring within a 1 1/4-year period is presented. Of these, 4 cases occurred within 5 months. All the patients were adult males. During the same period no similar pathology was observed in any female or child. Such a large number of cases occuring in so short a time is intriguing but we are unable to explain it. The treatment in all cases was with general supportive drugs, blood transfusion when needed and specific antibiotics. Local excision of the dead tissues and dressing with hydrogen peroxide and eusol gave satisfactory results.", "contents": "Fournier's gangrene: a report of 5 cases. A report of 5 cases of infective gangrene of the genitalia and adjacent tissues occuring within a 1 1/4-year period is presented. Of these, 4 cases occurred within 5 months. All the patients were adult males. During the same period no similar pathology was observed in any female or child. Such a large number of cases occuring in so short a time is intriguing but we are unable to explain it. The treatment in all cases was with general supportive drugs, blood transfusion when needed and specific antibiotics. Local excision of the dead tissues and dressing with hydrogen peroxide and eusol gave satisfactory results."} {"id": "PMID:1276680", "title": "A report on missile injuries in Cyprus 1974.", "content": "This paper details the experiences of the Princess Mary's Royal Air Force Hospital, Akrotiri (TPMH), during the last 6 months of 1974. TPMH was at that time a small hospital (120 beds) with a clinical staff of 17 situated in the south of Cyprus (fig. 1). The series comprises 71 patients injured by bullets, shrapnel, bomb-blasts or mines, drawn from British personnel, United Nations Forces and the local Cypriot military and civilian population, resulting from the coup d'\u00e9tat of 15 July 1974 and the subsequent Turkish invasion and air attacks. The casualties were often severely wounded beyound the capabilities of the local hospitals. They were mostly admitted during a 2-week period, but many required multiple operations extending over the next 3 or 4 months, and altogether 119 operations were carried out on 41 patients at TPMH. The organization of the limited resources of the medical, nursing and supporting staff is outlined. The correct treatment of missile wounds is emphasized. Resuscitation, wound excision, splintage and delayed suture or grafting are essential. Minimal morbidity and mortality are gained by a practised approach to the compounded results of violence.", "contents": "A report on missile injuries in Cyprus 1974. This paper details the experiences of the Princess Mary's Royal Air Force Hospital, Akrotiri (TPMH), during the last 6 months of 1974. TPMH was at that time a small hospital (120 beds) with a clinical staff of 17 situated in the south of Cyprus (fig. 1). The series comprises 71 patients injured by bullets, shrapnel, bomb-blasts or mines, drawn from British personnel, United Nations Forces and the local Cypriot military and civilian population, resulting from the coup d'\u00e9tat of 15 July 1974 and the subsequent Turkish invasion and air attacks. The casualties were often severely wounded beyound the capabilities of the local hospitals. They were mostly admitted during a 2-week period, but many required multiple operations extending over the next 3 or 4 months, and altogether 119 operations were carried out on 41 patients at TPMH. The organization of the limited resources of the medical, nursing and supporting staff is outlined. The correct treatment of missile wounds is emphasized. Resuscitation, wound excision, splintage and delayed suture or grafting are essential. Minimal morbidity and mortality are gained by a practised approach to the compounded results of violence."} {"id": "PMID:1276681", "title": "Sternoclavicular joint enlargement following block dissection.", "content": "The sternoclavicular joint may become enlarged subsequent to block dissection of the neck. It should be managed conservatively and does not require removal, although both clinical and X-ray appearances may give rise to suspicion of metastasis in the head of the clavicle. A hypothesis of the pathology of this unfamiliar condition is proposed.", "contents": "Sternoclavicular joint enlargement following block dissection. The sternoclavicular joint may become enlarged subsequent to block dissection of the neck. It should be managed conservatively and does not require removal, although both clinical and X-ray appearances may give rise to suspicion of metastasis in the head of the clavicle. A hypothesis of the pathology of this unfamiliar condition is proposed."} {"id": "PMID:1276683", "title": "Cryosurgical haemorrhoidectomy.", "content": "One hundred consecutive cases of haemorrhoids were treated by cryosurgery. The cryoprobe used is a convenient and simple instrument and gave a satisfactory result in 94 of the patients. The technique and complications are described. The patients were treated as outpatients, usually without anaesthesia.", "contents": "Cryosurgical haemorrhoidectomy. One hundred consecutive cases of haemorrhoids were treated by cryosurgery. The cryoprobe used is a convenient and simple instrument and gave a satisfactory result in 94 of the patients. The technique and complications are described. The patients were treated as outpatients, usually without anaesthesia."} {"id": "PMID:1276692", "title": "Non-accidental injury in children: what we do in Derby.", "content": "A scheme for dealing with cases of non-accidental injury in children in the Derby clinical area has been operating since 1971. A stable team of doctors, policemen, and social workers deal with each case. The parents are told at once that battering is suspected, and the police and social services department co-operate closely in establishing the facts, supporting the family, and protecting the child. A psychiatric assessment of the parents may help social workers decide on the long-term care of the child, and the forensic physician is invaluable if the case has to go to court. The team has made three recommendations about prevention and management of these cases: a specialist social service team should be set up to deal with these children and regain the skills and knowledge lost when children's departments were abolished in 1971; babies should be routinely weighed naked in infant welfare clinics; and juvenile courts should be able to order a psychiatric report on the parents in care proceedings.", "contents": "Non-accidental injury in children: what we do in Derby. A scheme for dealing with cases of non-accidental injury in children in the Derby clinical area has been operating since 1971. A stable team of doctors, policemen, and social workers deal with each case. The parents are told at once that battering is suspected, and the police and social services department co-operate closely in establishing the facts, supporting the family, and protecting the child. A psychiatric assessment of the parents may help social workers decide on the long-term care of the child, and the forensic physician is invaluable if the case has to go to court. The team has made three recommendations about prevention and management of these cases: a specialist social service team should be set up to deal with these children and regain the skills and knowledge lost when children's departments were abolished in 1971; babies should be routinely weighed naked in infant welfare clinics; and juvenile courts should be able to order a psychiatric report on the parents in care proceedings."} {"id": "PMID:1276693", "title": "Measurement of cardiac muscle relaxation in hypothyroidism.", "content": "The isovolumetric relaxation time of the left ventricle (IRT) in 20 hypothyroid patients (133 +/- (SE of mean) 4 ms) was significantly longer than that in 23 normal subjects (95 +/- 3 ms). During a trial of thyroxine replacement the IRT in 12 hypothyroid patients fell from 143 +/- 4 ms to 107 +/- 4 ms. The IRT seems to be a useful index of end-organ function in hypothyroidism.", "contents": "Measurement of cardiac muscle relaxation in hypothyroidism. The isovolumetric relaxation time of the left ventricle (IRT) in 20 hypothyroid patients (133 +/- (SE of mean) 4 ms) was significantly longer than that in 23 normal subjects (95 +/- 3 ms). During a trial of thyroxine replacement the IRT in 12 hypothyroid patients fell from 143 +/- 4 ms to 107 +/- 4 ms. The IRT seems to be a useful index of end-organ function in hypothyroidism."} {"id": "PMID:1276694", "title": "Relation between blood pressure, weight, and plasma sugar and serum insulin levels in schoolchildren aged 9-12 years in Westland, Holland.", "content": "In 2388 schoolchildren aged 9-12 years who took part in a study of cardiovascular risk factors in Westland, Holland, plasma sugar concentrations were found to be positively correlated with systolic and diastolic blood pressure, independently of weight. Serum cholesterol levels were also related to systolic blood pressure in boys, but much less strongly than plasma sugar levels. The relation between serum insulin and blood pressure, independent of plasma sugar, was weak. The relation between plasma sugar and systolic pressure existed for both sexes and regardless of whether measurements were made in the morning or afternoon; its association with diastolic pressure was weaker, and was not so consistent over all groups. These findings suggest that the relations between risk factors for coronary heart disease that exist in adults are already evident in childhood.", "contents": "Relation between blood pressure, weight, and plasma sugar and serum insulin levels in schoolchildren aged 9-12 years in Westland, Holland. In 2388 schoolchildren aged 9-12 years who took part in a study of cardiovascular risk factors in Westland, Holland, plasma sugar concentrations were found to be positively correlated with systolic and diastolic blood pressure, independently of weight. Serum cholesterol levels were also related to systolic blood pressure in boys, but much less strongly than plasma sugar levels. The relation between serum insulin and blood pressure, independent of plasma sugar, was weak. The relation between plasma sugar and systolic pressure existed for both sexes and regardless of whether measurements were made in the morning or afternoon; its association with diastolic pressure was weaker, and was not so consistent over all groups. These findings suggest that the relations between risk factors for coronary heart disease that exist in adults are already evident in childhood."} {"id": "PMID:1276695", "title": "Growth, behaviour, and educational achievement of Jamaican children with sickle-cell trait.", "content": "A longitudinal study of the mental and physical development of 200 children with normal haemoglobin and 21 with the sickle-cell trait was carried out in a small rural community in Jamaica. At about 2 and 10 years of age heights and weights showed no significant differences. At about 10 years of age classroom behaviour, sociability, and educational achievement were similar. The results suggest that the sickle-cell trait does not affect growth and mental development.", "contents": "Growth, behaviour, and educational achievement of Jamaican children with sickle-cell trait. A longitudinal study of the mental and physical development of 200 children with normal haemoglobin and 21 with the sickle-cell trait was carried out in a small rural community in Jamaica. At about 2 and 10 years of age heights and weights showed no significant differences. At about 10 years of age classroom behaviour, sociability, and educational achievement were similar. The results suggest that the sickle-cell trait does not affect growth and mental development."} {"id": "PMID:1276696", "title": "Comparison of intra-amniotic prostaglandin F2 alpha and hypertonic saline for induction of second-trimester abortion.", "content": "The efficacy and safety of intra-amniotic prostaglandin (PG) F2 alpha (25 mg repeated in six hours) and hypertonic saline (200 ml 20% NaC1) were compared in an international multicentre randomised study organised by the World Health Organisation's prostaglandin task force. Both hypertonic saline and PGF2alpha were found to be effective in terminating second-trimester pregnancy. The main advantage of PGF2alpha however, was its greater efficacy, with significantly higher success rates in the first 48 hours. Out of 717 women given PGF2alpha 614 (85-6%) aborted within 48 hours; by 24 hours 439 (61-2%) had aborted, and by 36 hours 574 (80-1%) had aborted. Out of 796 women given hypertonic saline 641 (80-5%) aborted within 48 hours; however, by 24 and 36 hours, respectively, only 161 (20-2%) and 462 (58%) had aborted. Although PGF2alpha was associated with a somewhat higher frequency of minor side effects than hypertonic saline, notably vomiting and diarrhoea, these were within acceptable limits. Only 59 women (8-2%) in the prostaglandin group had more than four episodes of vomiting and 11 (1-5%) more than four episodes of diarrhoea. Ohter side effects occurred only occasionally. No difference was found between the two groups in the frequency of incomplete abortion or excessive bleeding.", "contents": "Comparison of intra-amniotic prostaglandin F2 alpha and hypertonic saline for induction of second-trimester abortion. The efficacy and safety of intra-amniotic prostaglandin (PG) F2 alpha (25 mg repeated in six hours) and hypertonic saline (200 ml 20% NaC1) were compared in an international multicentre randomised study organised by the World Health Organisation's prostaglandin task force. Both hypertonic saline and PGF2alpha were found to be effective in terminating second-trimester pregnancy. The main advantage of PGF2alpha however, was its greater efficacy, with significantly higher success rates in the first 48 hours. Out of 717 women given PGF2alpha 614 (85-6%) aborted within 48 hours; by 24 hours 439 (61-2%) had aborted, and by 36 hours 574 (80-1%) had aborted. Out of 796 women given hypertonic saline 641 (80-5%) aborted within 48 hours; however, by 24 and 36 hours, respectively, only 161 (20-2%) and 462 (58%) had aborted. Although PGF2alpha was associated with a somewhat higher frequency of minor side effects than hypertonic saline, notably vomiting and diarrhoea, these were within acceptable limits. Only 59 women (8-2%) in the prostaglandin group had more than four episodes of vomiting and 11 (1-5%) more than four episodes of diarrhoea. Ohter side effects occurred only occasionally. No difference was found between the two groups in the frequency of incomplete abortion or excessive bleeding."} {"id": "PMID:1276735", "title": "Asthma deaths in Cardiff 1963-74: 90 deaths outside hospital.", "content": "In a detailed study of factors associated with death from bronchial asthma outside hospital 90 patients were investigated. The fatal attack was typically short and was most likely to occur in patients with a long history. Deaths often occurred before effective medical help was obtainable, but occasionally the patient or the doctor underestimated the severity of the attack. Patients especially at risk were those recently discharged from hospital after a previous attack. These deaths might be prevented by better patient education, a self-admission service for selected asthmatics, and by doctors using objective measurements of severity of asthma for the control of treatment. The underuse of corticosteroids is an important factor associated with death.", "contents": "Asthma deaths in Cardiff 1963-74: 90 deaths outside hospital. In a detailed study of factors associated with death from bronchial asthma outside hospital 90 patients were investigated. The fatal attack was typically short and was most likely to occur in patients with a long history. Deaths often occurred before effective medical help was obtainable, but occasionally the patient or the doctor underestimated the severity of the attack. Patients especially at risk were those recently discharged from hospital after a previous attack. These deaths might be prevented by better patient education, a self-admission service for selected asthmatics, and by doctors using objective measurements of severity of asthma for the control of treatment. The underuse of corticosteroids is an important factor associated with death."} {"id": "PMID:1276736", "title": "A relation between HLA antigens and clinical features in patients with acquired valvular heart disease.", "content": "Analysis of the HLA antigen patterns in patients with acquired valvular heart disease showed that antigens A29 and AW30/31 occurred more often in those patients whose valvular disease was not preceeded by a history of rheumatic fever or chorea. Patients with no rheumatic history but with antigen A29 or AW30/31 had clinical features that distinguished them from others with valvular disease--namely, (a) isolated mitral valve disease and (b) the need for surgery, often at an early age, after a relatively short duration of symptoms.", "contents": "A relation between HLA antigens and clinical features in patients with acquired valvular heart disease. Analysis of the HLA antigen patterns in patients with acquired valvular heart disease showed that antigens A29 and AW30/31 occurred more often in those patients whose valvular disease was not preceeded by a history of rheumatic fever or chorea. Patients with no rheumatic history but with antigen A29 or AW30/31 had clinical features that distinguished them from others with valvular disease--namely, (a) isolated mitral valve disease and (b) the need for surgery, often at an early age, after a relatively short duration of symptoms."} {"id": "PMID:1276737", "title": "Explanations for weight loss after ileojejunal bypass in gross obesity.", "content": "Twenty grossly obese patients underwent ileojejunal bypass operations. Measurements of calories lost in faeces showed that the malabsorption could not account for the weight loss. Furthermore, the malabsorption was not decreased two years after bypass, when weight was no longer being lost. Dietary restriction is therefore largely responsible for the weight loss and increased food intake for weight maintenance.", "contents": "Explanations for weight loss after ileojejunal bypass in gross obesity. Twenty grossly obese patients underwent ileojejunal bypass operations. Measurements of calories lost in faeces showed that the malabsorption could not account for the weight loss. Furthermore, the malabsorption was not decreased two years after bypass, when weight was no longer being lost. Dietary restriction is therefore largely responsible for the weight loss and increased food intake for weight maintenance."} {"id": "PMID:1276745", "title": "Prognosis and early management of birth injuries to the brachial plexus.", "content": "Twenty-four cases of birth injury to the brachial plexus were seen in 21 infants over 15 years. Obstetric complications were common, and in 11 cases traction was needed to deliver the shoulders. Three out of every four arms fully recovered after exercises. Splints were not needed. Reconstructive procedures were performed on three permanently paralysed arms when the children were aged about 4. There was no way of predicting which patients would recover. The muscles supplied by the suprascapular nerve were paralysed in all patients, and this paralysis persisted in those whose arms failed to recover fully.", "contents": "Prognosis and early management of birth injuries to the brachial plexus. Twenty-four cases of birth injury to the brachial plexus were seen in 21 infants over 15 years. Obstetric complications were common, and in 11 cases traction was needed to deliver the shoulders. Three out of every four arms fully recovered after exercises. Splints were not needed. Reconstructive procedures were performed on three permanently paralysed arms when the children were aged about 4. There was no way of predicting which patients would recover. The muscles supplied by the suprascapular nerve were paralysed in all patients, and this paralysis persisted in those whose arms failed to recover fully."} {"id": "PMID:1276746", "title": "Reducing outpatient attendances.", "content": "Outpatient attendances can be reduced by indirect contact by letter and telephone; this frees the consultant to concentrate on patients attending for the first time. Such methods have not yet been fully exploited in the National Health Service.", "contents": "Reducing outpatient attendances. Outpatient attendances can be reduced by indirect contact by letter and telephone; this frees the consultant to concentrate on patients attending for the first time. Such methods have not yet been fully exploited in the National Health Service."} {"id": "PMID:1276769", "title": "Course of patients discharged early after myocardial infarction.", "content": "Two hundred and seventy-one (76%) out of 358 survivors of infarction were discharged by the eighth hospital day, and 251 (93%) of them survived to six weeks after discharge. Six of the 20 patients who died between discharge and six weeks did so after readmission and 14 died as outpatients. All these patients who died at home had transmural infarction and four had diabetes. In inpatients successful resuscitation occurred mainly within the first 48 hours, with only three successful long-term results from all the patients who suffered arrest later. This suggests that more prolonged inpatient care would not have reduced the late mortality. These figures justify continuing with an early discharge policy for most patients, but coronary care should probably be more prolonged for patients with diabetes.", "contents": "Course of patients discharged early after myocardial infarction. Two hundred and seventy-one (76%) out of 358 survivors of infarction were discharged by the eighth hospital day, and 251 (93%) of them survived to six weeks after discharge. Six of the 20 patients who died between discharge and six weeks did so after readmission and 14 died as outpatients. All these patients who died at home had transmural infarction and four had diabetes. In inpatients successful resuscitation occurred mainly within the first 48 hours, with only three successful long-term results from all the patients who suffered arrest later. This suggests that more prolonged inpatient care would not have reduced the late mortality. These figures justify continuing with an early discharge policy for most patients, but coronary care should probably be more prolonged for patients with diabetes."} {"id": "PMID:1276770", "title": "Comparative study of short-term recovery of mental efficiency after anaesthesia.", "content": "Two common general anaesthetic techniques were compared to evaluate the time taken for the patient's mental efficiency to recover sufficiently for him to be escorted home after inguinal herniorrhaphy. Recovery in performance efficiency to at least 60% of the patient's own maximum is suggested as a criterion for discharge, and this needs a stay in hospital of seven to nine hours.", "contents": "Comparative study of short-term recovery of mental efficiency after anaesthesia. Two common general anaesthetic techniques were compared to evaluate the time taken for the patient's mental efficiency to recover sufficiently for him to be escorted home after inguinal herniorrhaphy. Recovery in performance efficiency to at least 60% of the patient's own maximum is suggested as a criterion for discharge, and this needs a stay in hospital of seven to nine hours."} {"id": "PMID:1276771", "title": "Study of reticuloendothelial phagocytic capacity in patients with cholestasis.", "content": "The phagocytic capacity of the reticuloendothelial system was studied by the clearance from the plasma of microaggregated iodinated human serum albumin. About half of the patients with cholestasis showed impaired Kupffer-cell phagocytosis. The finding may be relevant to the occurrence of surgical complications in patients with obstructive jaundice.", "contents": "Study of reticuloendothelial phagocytic capacity in patients with cholestasis. The phagocytic capacity of the reticuloendothelial system was studied by the clearance from the plasma of microaggregated iodinated human serum albumin. About half of the patients with cholestasis showed impaired Kupffer-cell phagocytosis. The finding may be relevant to the occurrence of surgical complications in patients with obstructive jaundice."} {"id": "PMID:1276774", "title": "Hepatitis B in retreat from dialysis units in United Kingdom in 1973. Public Health Laboratory Service Survey.", "content": "A prospective study of hepatitis in over two-thirds of the dialysis units in the United Kingdom has continued since 1968. After the introduction of a control and preventive programme in 1970 there was a sustained decline in the incidence of hepatitis B to the low level of 0-3% among patients and 0-1% among staff in 1973--a greater than tenfold decrease in four years. Comparisons with data from other countries suggest that the almost complete elimination of hepatitis B from dialysis units in the UK was due to the preventive programme.", "contents": "Hepatitis B in retreat from dialysis units in United Kingdom in 1973. Public Health Laboratory Service Survey. A prospective study of hepatitis in over two-thirds of the dialysis units in the United Kingdom has continued since 1968. After the introduction of a control and preventive programme in 1970 there was a sustained decline in the incidence of hepatitis B to the low level of 0-3% among patients and 0-1% among staff in 1973--a greater than tenfold decrease in four years. Comparisons with data from other countries suggest that the almost complete elimination of hepatitis B from dialysis units in the UK was due to the preventive programme."} {"id": "PMID:1276775", "title": "Out-of-hours calls in a Leicestershire practice.", "content": "In one year, 920 \"out-of-hours\" calls were received by a partnership of three general practitioners working from a health centre in semi-rural Leicestershire. The partners on duty saw 588 patients. Out of 898 patients on whom information was available only 75 (8-5%) were referred to hospital, mainly as casualties. The results are compared with a study of deputising services, and it is concluded that a partnership covering its own out-of-hours calls can provide a more personal service and appears to make fewer demands on NHS resources.", "contents": "Out-of-hours calls in a Leicestershire practice. In one year, 920 \"out-of-hours\" calls were received by a partnership of three general practitioners working from a health centre in semi-rural Leicestershire. The partners on duty saw 588 patients. Out of 898 patients on whom information was available only 75 (8-5%) were referred to hospital, mainly as casualties. The results are compared with a study of deputising services, and it is concluded that a partnership covering its own out-of-hours calls can provide a more personal service and appears to make fewer demands on NHS resources."} {"id": "PMID:1276818", "title": "High-dose corticosteroids in severe acute asthma.", "content": "Twenty-six patients admitted to hospital for treatment of severe exacerbations of asthma unresponsive to bronchodilators were assigned to high-, medium-, or low-dose corticosteroid treatment regimens. The rates of recovery were assessed by changes in pulse rate, peak expiratory flow rate, and spirometric measurements and were not related to the dose of corticosteroids given. Very high systemic doses of corticosteroids do not offer significant advantages in treating severe exacerbations of asthma.", "contents": "High-dose corticosteroids in severe acute asthma. Twenty-six patients admitted to hospital for treatment of severe exacerbations of asthma unresponsive to bronchodilators were assigned to high-, medium-, or low-dose corticosteroid treatment regimens. The rates of recovery were assessed by changes in pulse rate, peak expiratory flow rate, and spirometric measurements and were not related to the dose of corticosteroids given. Very high systemic doses of corticosteroids do not offer significant advantages in treating severe exacerbations of asthma."} {"id": "PMID:1276819", "title": "Superficial carcinoma of the stomach.", "content": "Nine cases of superficial gastric carcinoma have been detected with upper gastrointestinal endoscopy in Bristol in the past two years. This contrasted with only six cases found from postoperative gastrectomy specimens examined in the previous eight years. It is often difficult to distinguish a superficial carcinoma from a benign ulcer, and endoscopic diagnosis is effective only if multiple biopsy specimens are taken. Endoscopy should also be repeated and multiple specimens taken until the lesion has healed; even malignant ulcers may heal, and any healed area that is depressed with interrupted mucosal folds should be suspected of malignancy. The endoscopic and histological appearances, the age of the patients, and the clinical behaviour of the disease resembled descriptions of the disease, principally from Japan. Superficial gastric carcinoma is probably under-diagnosed in Britain.", "contents": "Superficial carcinoma of the stomach. Nine cases of superficial gastric carcinoma have been detected with upper gastrointestinal endoscopy in Bristol in the past two years. This contrasted with only six cases found from postoperative gastrectomy specimens examined in the previous eight years. It is often difficult to distinguish a superficial carcinoma from a benign ulcer, and endoscopic diagnosis is effective only if multiple biopsy specimens are taken. Endoscopy should also be repeated and multiple specimens taken until the lesion has healed; even malignant ulcers may heal, and any healed area that is depressed with interrupted mucosal folds should be suspected of malignancy. The endoscopic and histological appearances, the age of the patients, and the clinical behaviour of the disease resembled descriptions of the disease, principally from Japan. Superficial gastric carcinoma is probably under-diagnosed in Britain."} {"id": "PMID:1276820", "title": "Whole-body in-vivo neutron activation analysis in assessing treatment of renal osteodystrophy with 1-alpha-hydroxycholecalciferol.", "content": "Four selected adults with different patterns of osteodystrophy receiving regular dialysis were treated with 1-alpha-hydroxycholecalciferol (1-alpha-OHD3) 0-5-2 mug/day for 10 to 12 months. In two patients, one with osteitis fibrosa and the other with osteomalacia, significant biochemical, radiological, and histological improvements occurred, and total body calcium measured by in-vivo neutron activation analysis increased. In two patients, in whom there were no increases of whole-body calcium, neither biochemical improvement nor healing of bone lesions occurred during the study; in one of these patients the effect of 1-alpha-OHD3 on bone resorption may have contributed to loss of body calcium and deterioration of bone disease. 1-alpha-OHD3 may therefore be a valuable adjunct in the treatment of only some patients with renal osteodystrophy. Whole-body in-vivo neutron activation seems to provide a sensitive and non-invasive index of early response to treatment.", "contents": "Whole-body in-vivo neutron activation analysis in assessing treatment of renal osteodystrophy with 1-alpha-hydroxycholecalciferol. Four selected adults with different patterns of osteodystrophy receiving regular dialysis were treated with 1-alpha-hydroxycholecalciferol (1-alpha-OHD3) 0-5-2 mug/day for 10 to 12 months. In two patients, one with osteitis fibrosa and the other with osteomalacia, significant biochemical, radiological, and histological improvements occurred, and total body calcium measured by in-vivo neutron activation analysis increased. In two patients, in whom there were no increases of whole-body calcium, neither biochemical improvement nor healing of bone lesions occurred during the study; in one of these patients the effect of 1-alpha-OHD3 on bone resorption may have contributed to loss of body calcium and deterioration of bone disease. 1-alpha-OHD3 may therefore be a valuable adjunct in the treatment of only some patients with renal osteodystrophy. Whole-body in-vivo neutron activation seems to provide a sensitive and non-invasive index of early response to treatment."} {"id": "PMID:1276821", "title": "Headache after carotid endarterectomy.", "content": "Forty-eight hours after undergoing a successful right carotid endarectomy a patient complained of headache in and behind the right eye radiating to the temple and forehead. The onset of headache was sudden, and the pain was severe and throbbing. After three weeks of regular four- to eight-hour attacks each day the headaches gradually became less frequent. Two months after operation they had disappeared completely. Headache as a complication of endarterectomy is rare, but typically it is vascular and subsides spontaneously in one to six months. If a predisposition to migraine were a precipitating factor many more cases would be expected. No possible explanation for for headache after carotid prearterectomy can account adequately for its apparent rarity.", "contents": "Headache after carotid endarterectomy. Forty-eight hours after undergoing a successful right carotid endarectomy a patient complained of headache in and behind the right eye radiating to the temple and forehead. The onset of headache was sudden, and the pain was severe and throbbing. After three weeks of regular four- to eight-hour attacks each day the headaches gradually became less frequent. Two months after operation they had disappeared completely. Headache as a complication of endarterectomy is rare, but typically it is vascular and subsides spontaneously in one to six months. If a predisposition to migraine were a precipitating factor many more cases would be expected. No possible explanation for for headache after carotid prearterectomy can account adequately for its apparent rarity."} {"id": "PMID:1276825", "title": "Programmed investigation unit.", "content": "The programmed investigation unit (PIU) is a inpatient unit where a full range of investigational medicine can be organised. It provides the basic minimum nursing care and is suitable for ambulant patients who can care for themselves. Requests for admission to the PIU at the Royal Victoria Infirmary, Newcastle upon Tyne, come directly from clinical units, and the staff of these units perform some of the tests and remain responsible for the patient while she is in the unit. At present the unit caters only for female medical patients. The average waiting time for admission is three weeks, and because the unit now deals with most investigations the waiting time for admission to the female general medical wards has fallen considerably. The staff of the unit have gained expertise in diagnostic methods, while the nurses of general medical wards have been free to concentrate on nursing those patients who need it. Separating patients who need investigations from those on general medical wards seems a logical way of using resources and staff to best effect.", "contents": "Programmed investigation unit. The programmed investigation unit (PIU) is a inpatient unit where a full range of investigational medicine can be organised. It provides the basic minimum nursing care and is suitable for ambulant patients who can care for themselves. Requests for admission to the PIU at the Royal Victoria Infirmary, Newcastle upon Tyne, come directly from clinical units, and the staff of these units perform some of the tests and remain responsible for the patient while she is in the unit. At present the unit caters only for female medical patients. The average waiting time for admission is three weeks, and because the unit now deals with most investigations the waiting time for admission to the female general medical wards has fallen considerably. The staff of the unit have gained expertise in diagnostic methods, while the nurses of general medical wards have been free to concentrate on nursing those patients who need it. Separating patients who need investigations from those on general medical wards seems a logical way of using resources and staff to best effect."} {"id": "PMID:1276833", "title": "Hypophosphataemic osteomalacia in patients receiving haemodialysis.", "content": "Four patients had symptomless osteomalacia at the time of starting regular haemodialysis. After 21-40 months they became hypophosphataemic and developed disabling skeletal symptoms. In each case an exacerbation of histological osteomalacia was shown. Symptoms improved after measures designed to raise serum inorganic phosphate concentrations or vitamin D administration, or both. Patients undergoing maintenance haemodialysis should have their serum phosphate and alkaline phosphatase levels monitored every month. Predialysis phosphate levels below 1 mmol/1 (3 mg/100 ml) and rising serum alkaline phosphatase concentrations are danger signals. If the diagnosis is confirmed early aggressive treatment should be started.", "contents": "Hypophosphataemic osteomalacia in patients receiving haemodialysis. Four patients had symptomless osteomalacia at the time of starting regular haemodialysis. After 21-40 months they became hypophosphataemic and developed disabling skeletal symptoms. In each case an exacerbation of histological osteomalacia was shown. Symptoms improved after measures designed to raise serum inorganic phosphate concentrations or vitamin D administration, or both. Patients undergoing maintenance haemodialysis should have their serum phosphate and alkaline phosphatase levels monitored every month. Predialysis phosphate levels below 1 mmol/1 (3 mg/100 ml) and rising serum alkaline phosphatase concentrations are danger signals. If the diagnosis is confirmed early aggressive treatment should be started."} {"id": "PMID:1276834", "title": "Immediate plasma renin response to propranolol: differentiation between essential and renal hypertension.", "content": "The immediate short-term effect on plasma renin activity of intravenous injection of propranolol was studied in 31 normal subjects and 166 hypertensive patients. In patients with essential hypertension and normal subjects plasma renin activity fell considerably within 15 minutes; the fall was directly proportional to initial plasma renin levels. In contrast, in patients with renal hypertension the fall was much less pronounced or totally absent. These differences in response to propranolol provide, though presently only on a group basis, a biochemical means of differentiating between patients with renal hypertension and those with essential hypertension. The observations also indicate that, unlike normal subjects and patients with essential hypertension, in patients with renal hypertension sympathetic activity plays no part in the control of basal plasma renin levels.", "contents": "Immediate plasma renin response to propranolol: differentiation between essential and renal hypertension. The immediate short-term effect on plasma renin activity of intravenous injection of propranolol was studied in 31 normal subjects and 166 hypertensive patients. In patients with essential hypertension and normal subjects plasma renin activity fell considerably within 15 minutes; the fall was directly proportional to initial plasma renin levels. In contrast, in patients with renal hypertension the fall was much less pronounced or totally absent. These differences in response to propranolol provide, though presently only on a group basis, a biochemical means of differentiating between patients with renal hypertension and those with essential hypertension. The observations also indicate that, unlike normal subjects and patients with essential hypertension, in patients with renal hypertension sympathetic activity plays no part in the control of basal plasma renin levels."} {"id": "PMID:1276835", "title": "Enhanced drug metabolism in cigarette smokers.", "content": "The effect of cigarette smoking on salivary antipyrine disappearance rate, and as an index of hepatic drug metabolism, was studied in 42 healthy subjects. Antipyrine half life was significantly shorter in smokers compared with non-smokers. To determine whether this difference was due solely to tobacco consumption eight subjects were restudied two months after they stopped smoking. The mean antipyrine disappearance rate in this group increased by 23% in contrast to that of a control group, which did not alter. Cigarette smoking contributes to the considerable variation in interindividual rates of drug metabolism.", "contents": "Enhanced drug metabolism in cigarette smokers. The effect of cigarette smoking on salivary antipyrine disappearance rate, and as an index of hepatic drug metabolism, was studied in 42 healthy subjects. Antipyrine half life was significantly shorter in smokers compared with non-smokers. To determine whether this difference was due solely to tobacco consumption eight subjects were restudied two months after they stopped smoking. The mean antipyrine disappearance rate in this group increased by 23% in contrast to that of a control group, which did not alter. Cigarette smoking contributes to the considerable variation in interindividual rates of drug metabolism."} {"id": "PMID:1276841", "title": "Adder bites in Britain.", "content": "Ninety-five cases of adder bite that have occurred in Britain over the past 100 years are reviewed. Most bites occurred in men who foolishly picked up the adder. Three-quarters of the victims reached hospital within two hours of the bite. When venom is injected the early symptoms include local swelling and discoloration, vomiting, diarrhoea, and early collapse, which often resolves spontaneously. In severe poisoning persistent or recurrent shock is the main feature. Children recover quickly but adults may take weeks or months to recover, during which there may be considerable disability in the bitten limb. Deaths are rare: only 14 deaths from poisoning were recorded in the past 100 years. In England and Wales only one death from adder bite was recorded in 1950-72, but there were 61 deaths from bee or wasp stings. In most cases simple symptomatic treatment is enough, but all patients should be carefully monitored. With persistent or recurrent shock Zagreb antivenom is indicated; and it should also be considered in adults seen within two hours of the bite to minimise morbidity from local effects.", "contents": "Adder bites in Britain. Ninety-five cases of adder bite that have occurred in Britain over the past 100 years are reviewed. Most bites occurred in men who foolishly picked up the adder. Three-quarters of the victims reached hospital within two hours of the bite. When venom is injected the early symptoms include local swelling and discoloration, vomiting, diarrhoea, and early collapse, which often resolves spontaneously. In severe poisoning persistent or recurrent shock is the main feature. Children recover quickly but adults may take weeks or months to recover, during which there may be considerable disability in the bitten limb. Deaths are rare: only 14 deaths from poisoning were recorded in the past 100 years. In England and Wales only one death from adder bite was recorded in 1950-72, but there were 61 deaths from bee or wasp stings. In most cases simple symptomatic treatment is enough, but all patients should be carefully monitored. With persistent or recurrent shock Zagreb antivenom is indicated; and it should also be considered in adults seen within two hours of the bite to minimise morbidity from local effects."} {"id": "PMID:1276844", "title": "The elderly mentally ill--whose responsibility?", "content": "The elderly mentally ill make considerable demands on health and social services. To evaluate the need for these services a one-day census of all people aged 65 and over was carried out in an area containing 220 000 people (40 000 over 65). Data were obtained on the nursing needs and psychiatric state of the 2162 elderly people in hospital or local authority residential homes for the elderly, or living at home receiving care from the community nursing service. One-third were classified as having psychiatric problems, more than half of them being outside hospital. Residential homes and community nurses play a significant part in caring for the elderly mentally ill, and an integrated but flexible manpower policy is important.", "contents": "The elderly mentally ill--whose responsibility? The elderly mentally ill make considerable demands on health and social services. To evaluate the need for these services a one-day census of all people aged 65 and over was carried out in an area containing 220 000 people (40 000 over 65). Data were obtained on the nursing needs and psychiatric state of the 2162 elderly people in hospital or local authority residential homes for the elderly, or living at home receiving care from the community nursing service. One-third were classified as having psychiatric problems, more than half of them being outside hospital. Residential homes and community nurses play a significant part in caring for the elderly mentally ill, and an integrated but flexible manpower policy is important."} {"id": "PMID:1276863", "title": "Some characteristics of homosexual men.", "content": "Although recognition of homosexuals is often important, many doctors lack the necessary skill or experience, so to assist them a group of 5,302 men was surveyed using a computer-based data system and 9-1 per cent. were recorded as homosexual. Analysis showed a relatively high proportion of homosexuals among men with syphilis and gonorrhoea, and a low proportion among men with nonspecific genital infection (non-specific urethritis and proctitis) and other infections. All men with secondary syphilis were homosexual. A relatively high proportion of men born in Eire, Spain, and North America were homosexual and a relatively high proportion of men living in the West End of London were homosexual. While these findings will be of most value to those working in STD clinics in London they may also be helpful to those working elsewhere and in other disciplines.", "contents": "Some characteristics of homosexual men. Although recognition of homosexuals is often important, many doctors lack the necessary skill or experience, so to assist them a group of 5,302 men was surveyed using a computer-based data system and 9-1 per cent. were recorded as homosexual. Analysis showed a relatively high proportion of homosexuals among men with syphilis and gonorrhoea, and a low proportion among men with nonspecific genital infection (non-specific urethritis and proctitis) and other infections. All men with secondary syphilis were homosexual. A relatively high proportion of men born in Eire, Spain, and North America were homosexual and a relatively high proportion of men living in the West End of London were homosexual. While these findings will be of most value to those working in STD clinics in London they may also be helpful to those working elsewhere and in other disciplines."} {"id": "PMID:1276864", "title": "Changing pattern of male homosexual registrations in a venereal disease clinic, 1964-1974.", "content": "Registrations of heterosexual and homosexual men, with and without gonorrhoea, as recorded at Ward 34, Newcastle General Hospital, from 1964 to 1974, show substantial rises. During this time, the number of cases of gonorrhoea in men, both heterosexually and homosecually acquired, has approximately doubled. However, the incidence of individual gonococcal re-infection would not appear to have changed significantly. More men attend with non-venereal conditions and show an increasing willingness to return. A greater co-operation between homosexuals with gonorrhoea and the social unit has evolved and a greater number of sexual contacts are now traced and examined.", "contents": "Changing pattern of male homosexual registrations in a venereal disease clinic, 1964-1974. Registrations of heterosexual and homosexual men, with and without gonorrhoea, as recorded at Ward 34, Newcastle General Hospital, from 1964 to 1974, show substantial rises. During this time, the number of cases of gonorrhoea in men, both heterosexually and homosecually acquired, has approximately doubled. However, the incidence of individual gonococcal re-infection would not appear to have changed significantly. More men attend with non-venereal conditions and show an increasing willingness to return. A greater co-operation between homosexuals with gonorrhoea and the social unit has evolved and a greater number of sexual contacts are now traced and examined."} {"id": "PMID:1276865", "title": "Pharyngeal gonorrhoea in homosexuals.", "content": "In a prospective survey of 106 male homosexuals, investigations included smears and cultures of material taken from the tonsillar areas. A diagnosis of gonococcal pharyngitis was made in six cases. This is the largest series so far reported from England. The prevalence of gonorrhoea nd less conventional sexual practices must prompt us to investigate gonococcal infection in sites remote from the ano-genital region.", "contents": "Pharyngeal gonorrhoea in homosexuals. In a prospective survey of 106 male homosexuals, investigations included smears and cultures of material taken from the tonsillar areas. A diagnosis of gonococcal pharyngitis was made in six cases. This is the largest series so far reported from England. The prevalence of gonorrhoea nd less conventional sexual practices must prompt us to investigate gonococcal infection in sites remote from the ano-genital region."} {"id": "PMID:1276866", "title": "Single oral dose of 1-5g. talampicillin in the treatment of gonorrhoea.", "content": "81 patients have been treated with single oral doses of 1-5 g. (6 tablets) of talampicillin without probenecid. The failure rate amongst those followed was only 4-2 per cent. No side-effects were reported. These results were superior to those obtained with 2-0g. or equivalent of ampicillin, amoxycillin, or pivampicillin with probenecid. Talampicillin is thus the most potent ampicillin-like antibiotic so far available for the treatment of gonorrhoea and is capable of curing the disease with a smaller single dose without probenecid than is necessary for other preparations.", "contents": "Single oral dose of 1-5g. talampicillin in the treatment of gonorrhoea. 81 patients have been treated with single oral doses of 1-5 g. (6 tablets) of talampicillin without probenecid. The failure rate amongst those followed was only 4-2 per cent. No side-effects were reported. These results were superior to those obtained with 2-0g. or equivalent of ampicillin, amoxycillin, or pivampicillin with probenecid. Talampicillin is thus the most potent ampicillin-like antibiotic so far available for the treatment of gonorrhoea and is capable of curing the disease with a smaller single dose without probenecid than is necessary for other preparations."} {"id": "PMID:1276867", "title": "Prostitution in Sheffield.", "content": "Prostitution in Sheffield, a city with over half a million population, has been reviewed in its legal, social work, and medical aspects. The years studied were 1960-73. The medical studies were confined to the years 1968-72. Prosecutions for soliciting increased steadily during the study period. The trend was more marked locally than nationally and was associated both with increased police activity and, more recently, with the pursuit of a socially-aware sentencing, probationary, and social work policy. During the 5-year medical study, sixty prostitutes were seen. Using gonorrhoea as an index they were found to hazard the health of both themselves and others. Recurrent infection was the rule amongst them and 40 per cent. suffered salpingitis. In epidemiological terms our findings show that the vector role of prostitutes continues undiminished. The alleged decline in their role is relative only and not real. They accounted for one in six of locally acquired gonococcal infections in heterosexual men. The study indicates the need for the regular monitoring of the social phenomenon or prostitution and for the detailed study of all its aspects on a national basis.", "contents": "Prostitution in Sheffield. Prostitution in Sheffield, a city with over half a million population, has been reviewed in its legal, social work, and medical aspects. The years studied were 1960-73. The medical studies were confined to the years 1968-72. Prosecutions for soliciting increased steadily during the study period. The trend was more marked locally than nationally and was associated both with increased police activity and, more recently, with the pursuit of a socially-aware sentencing, probationary, and social work policy. During the 5-year medical study, sixty prostitutes were seen. Using gonorrhoea as an index they were found to hazard the health of both themselves and others. Recurrent infection was the rule amongst them and 40 per cent. suffered salpingitis. In epidemiological terms our findings show that the vector role of prostitutes continues undiminished. The alleged decline in their role is relative only and not real. They accounted for one in six of locally acquired gonococcal infections in heterosexual men. The study indicates the need for the regular monitoring of the social phenomenon or prostitution and for the detailed study of all its aspects on a national basis."} {"id": "PMID:1276869", "title": "The effects of centrifugation on the morphology of the lateral vestibular nucleus in the rat: a light and electron microscopic study.", "content": "Very little is known about structural changes in the central nervous system following exposure to increased g forces. Sprague-Dawley rats were centrifuged at Ames Research Center at 2.76-4.15 x g for periods ranging from 4 days to 21 months. The lateral vestibular nuclei were processed for electron microscopy and examined for evidence of structural alteration as a result of centrifugation. The number of filamentous nuclear inclusions, varicosities, and relative number of axosomatic synaptic terminals containing flattened vesicles (presumed inhibitory in function) increased in centrifuged rats. Altered mitochondria also were noted in that cell bodies of Deiters' neurons. Neuroaxonal dystrophy (NAD) was found in long-term centrifuged rats and was characterized by axons filled with reticulated mitochondria. The NAD found in the lateral vestibular nuclei of centrifuged rats is different from that seen in the dorsal column nuclei of aged mice.", "contents": "The effects of centrifugation on the morphology of the lateral vestibular nucleus in the rat: a light and electron microscopic study. Very little is known about structural changes in the central nervous system following exposure to increased g forces. Sprague-Dawley rats were centrifuged at Ames Research Center at 2.76-4.15 x g for periods ranging from 4 days to 21 months. The lateral vestibular nuclei were processed for electron microscopy and examined for evidence of structural alteration as a result of centrifugation. The number of filamentous nuclear inclusions, varicosities, and relative number of axosomatic synaptic terminals containing flattened vesicles (presumed inhibitory in function) increased in centrifuged rats. Altered mitochondria also were noted in that cell bodies of Deiters' neurons. Neuroaxonal dystrophy (NAD) was found in long-term centrifuged rats and was characterized by axons filled with reticulated mitochondria. The NAD found in the lateral vestibular nuclei of centrifuged rats is different from that seen in the dorsal column nuclei of aged mice."} {"id": "PMID:1276870", "title": "Postnatal development of acetylcholinesterase in the caudate-putamen nucleus and substantia nigra of rats.", "content": "The postnatal development of acetylcholinesterase (AChE, EC 3.1.1.7) and NADH-diaphorase was examined in the caudate-putamen nucleus and substantia nigra of rats ranging from 3 to 90 days in age. From 3 to 15 days post partum islands of AChE and NADH-diaphorase activity were observed in the caudate-putamen nucleus. Individual neuronal somata could also be seen in AChE-stained sections up to 15 days. At later ages neuropil staining became increasingly dense, and this presumably accounted for the infrequent visualization of cell bodies in the brains of older animals. During development AChE appeared in the caudate-putamen nucleus in a lateral to medial topographic order; analogously, enzyme staining in the neostriatum reappeared in the same lateral to medial topographic order in adult rats following irreversible AChE inhibition by intramuscularly injected bis-(1-methylethyl)phosphorofluoridate (di-isopropylfluorophosphate: DFP). Furthermore, DFP treatment in mature animals revealed the presence of AChE in striatal neurons having morphologies similar to those observed in newborn rats. A similar time-course of postnatal AChE development was observed in the substantia nigra. In both the pars compacta and pars reticulata individual cell bodies, which were visible at early ages (3-10 days), became increasingly obscured at later times after birth by extra-somata staining. Between the 6th and 15th postnatal days AChE-containing fibers were seen projecting apparently from pars compacta into pars reticulata. Comparison of the present results with histochemical data of other investigators on the postnatal development of monoamines indicated the likelihood of cholinergicmonoaminergic interactions in the neostriatum and substantia nigra.", "contents": "Postnatal development of acetylcholinesterase in the caudate-putamen nucleus and substantia nigra of rats. The postnatal development of acetylcholinesterase (AChE, EC 3.1.1.7) and NADH-diaphorase was examined in the caudate-putamen nucleus and substantia nigra of rats ranging from 3 to 90 days in age. From 3 to 15 days post partum islands of AChE and NADH-diaphorase activity were observed in the caudate-putamen nucleus. Individual neuronal somata could also be seen in AChE-stained sections up to 15 days. At later ages neuropil staining became increasingly dense, and this presumably accounted for the infrequent visualization of cell bodies in the brains of older animals. During development AChE appeared in the caudate-putamen nucleus in a lateral to medial topographic order; analogously, enzyme staining in the neostriatum reappeared in the same lateral to medial topographic order in adult rats following irreversible AChE inhibition by intramuscularly injected bis-(1-methylethyl)phosphorofluoridate (di-isopropylfluorophosphate: DFP). Furthermore, DFP treatment in mature animals revealed the presence of AChE in striatal neurons having morphologies similar to those observed in newborn rats. A similar time-course of postnatal AChE development was observed in the substantia nigra. In both the pars compacta and pars reticulata individual cell bodies, which were visible at early ages (3-10 days), became increasingly obscured at later times after birth by extra-somata staining. Between the 6th and 15th postnatal days AChE-containing fibers were seen projecting apparently from pars compacta into pars reticulata. Comparison of the present results with histochemical data of other investigators on the postnatal development of monoamines indicated the likelihood of cholinergicmonoaminergic interactions in the neostriatum and substantia nigra."} {"id": "PMID:1276871", "title": "Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways.", "content": "The behavior of rats with selective lesions of either the dorsal (B7), median (B8), or lateral (B9) raphe nuclei was compared to that of sham-lesioned controls in a variety of experimental situations. As described previously, the extent of damage to the midbrain raphe nuclei was determined by fluorescence histochemistry, and the tryptophan hydroxylase and tyrosine hydroxylase activities of 6 forebrain regions were measured for each rat. None of the lesions affected tyrosine hydroxylase activity. Lesions of B7, which reduced tryptophan hydroxylase in the striatum, thalamus, cortex, and hypothalamus, had no significant effect on any of the behavioral measures. Lesions of B9, although twice as large, neither reduced forebrain tryptophan hydroxylase significantly nor affected any of the behavioral variables. However, B8 lesions, which reduced hippocampal, septal, cortical, and hypothalamic tryptophan hydroxylase, had behavioral effects similar to those reported after combined raphe lesions parachlorophenylalanine. Median raphe-lesioned rats were hyperactive when placed in a novel environment and throughout the dark phase of the light/dark cycle. With respect to locomotor activity, B8-lesioned rats were also hyper-responsive to amphetamine. When placed in a stabilimeter and subjected to repeated air puff stimuli, rats with B8 lesions exhibited larger startle responses. Furthermore, only B8-lesioned animals perseverated when given two unreinforced trials in a Y-maze. All these histologic, biochemical, and behavioral variables were assessed individually for all 39 animals, and a multivariate correlational analysis incorporating the data of this and the preceding paper is presented here. These experiments suggest that the mesolimbic serotonergic pathway originating in B8 subserves some of the inhibition necessary to dampen behavioral responsivity.", "contents": "Behavioral studies following lesions of the mesolimbic and mesostriatal serotonergic pathways. The behavior of rats with selective lesions of either the dorsal (B7), median (B8), or lateral (B9) raphe nuclei was compared to that of sham-lesioned controls in a variety of experimental situations. As described previously, the extent of damage to the midbrain raphe nuclei was determined by fluorescence histochemistry, and the tryptophan hydroxylase and tyrosine hydroxylase activities of 6 forebrain regions were measured for each rat. None of the lesions affected tyrosine hydroxylase activity. Lesions of B7, which reduced tryptophan hydroxylase in the striatum, thalamus, cortex, and hypothalamus, had no significant effect on any of the behavioral measures. Lesions of B9, although twice as large, neither reduced forebrain tryptophan hydroxylase significantly nor affected any of the behavioral variables. However, B8 lesions, which reduced hippocampal, septal, cortical, and hypothalamic tryptophan hydroxylase, had behavioral effects similar to those reported after combined raphe lesions parachlorophenylalanine. Median raphe-lesioned rats were hyperactive when placed in a novel environment and throughout the dark phase of the light/dark cycle. With respect to locomotor activity, B8-lesioned rats were also hyper-responsive to amphetamine. When placed in a stabilimeter and subjected to repeated air puff stimuli, rats with B8 lesions exhibited larger startle responses. Furthermore, only B8-lesioned animals perseverated when given two unreinforced trials in a Y-maze. All these histologic, biochemical, and behavioral variables were assessed individually for all 39 animals, and a multivariate correlational analysis incorporating the data of this and the preceding paper is presented here. These experiments suggest that the mesolimbic serotonergic pathway originating in B8 subserves some of the inhibition necessary to dampen behavioral responsivity."} {"id": "PMID:1276872", "title": "Ontogeny of leg motor output in the chick embryo: a neural analysis.", "content": "The motor output of the leg of the chick embryo during hatching (20 days of incubation) was characterized using electromyographic (EMG) recordings from identified knee and ankle muscles. A highly coordinated pattern of motor output was found. It was therefore used as a standard against which to compare the motor output from younger embryos (7, 9, 13, 17 and 19 days of incubation). Despite large differences in some aspects of the EMG records from embryos of different ages, consistent patterns of muscle activation were observed. Quantitative analysis of phase and latency relationships between pairs of muscles indicated that at least some elements of the neural circuitry involved in generating the hatching motor output may be laid down very early in development. Duration vs. latency plots revealed that there is a gradual refinement in the temporal pattern of alternation between antagonist muscles during development.", "contents": "Ontogeny of leg motor output in the chick embryo: a neural analysis. The motor output of the leg of the chick embryo during hatching (20 days of incubation) was characterized using electromyographic (EMG) recordings from identified knee and ankle muscles. A highly coordinated pattern of motor output was found. It was therefore used as a standard against which to compare the motor output from younger embryos (7, 9, 13, 17 and 19 days of incubation). Despite large differences in some aspects of the EMG records from embryos of different ages, consistent patterns of muscle activation were observed. Quantitative analysis of phase and latency relationships between pairs of muscles indicated that at least some elements of the neural circuitry involved in generating the hatching motor output may be laid down very early in development. Duration vs. latency plots revealed that there is a gradual refinement in the temporal pattern of alternation between antagonist muscles during development."} {"id": "PMID:1276873", "title": "Neuronal activity with relation to cardiac rhythm in the lower brain stem of the dog.", "content": "Extracellular recordings of reticular neurons in the lower brain stem were performed in anesthetized dogs. Thirty out of 131 neurons showed rhythms of about 2-4 c/sec which were similar to heart or to EEG rhythms. By means of post-event-time histograms, correlations to the EEG delta-theta rhythm could be found in some neurons. These results were published elsewhere. Fixed relations of the neuronal activity to the cardiac rhythm could be verified in 7 neurons. Two neurons showed maxima 70 msec and 120 msec, respectively, after the beginning of the pulse wave. Two neurons showed minima after 110 msec and 130 msec, respectively. Three pulse-rhythmical neurons could not be classified in this way. This rhythmicity was changing or vanishing during the course of registration, but it could be strengthened experimentally by blood-pressure increase. It was shown that these neurons receive inputs from cardiovascular afferents and therefore are blood-pressure dependent neurons. From the finding that pulse-rhythmical modulation is different at different times under the same blood-pressure levels, it is assumed that there are varying strong influences from other systems to these neurons. The fact that these neurons are influenced by cardiovascular afferents does not mean, however, that they are cardiovascular neurons exclusively. It is suggested that blood-pressure reticular neurons may belong to the cardiovascular system as well as to other brain stem systems.", "contents": "Neuronal activity with relation to cardiac rhythm in the lower brain stem of the dog. Extracellular recordings of reticular neurons in the lower brain stem were performed in anesthetized dogs. Thirty out of 131 neurons showed rhythms of about 2-4 c/sec which were similar to heart or to EEG rhythms. By means of post-event-time histograms, correlations to the EEG delta-theta rhythm could be found in some neurons. These results were published elsewhere. Fixed relations of the neuronal activity to the cardiac rhythm could be verified in 7 neurons. Two neurons showed maxima 70 msec and 120 msec, respectively, after the beginning of the pulse wave. Two neurons showed minima after 110 msec and 130 msec, respectively. Three pulse-rhythmical neurons could not be classified in this way. This rhythmicity was changing or vanishing during the course of registration, but it could be strengthened experimentally by blood-pressure increase. It was shown that these neurons receive inputs from cardiovascular afferents and therefore are blood-pressure dependent neurons. From the finding that pulse-rhythmical modulation is different at different times under the same blood-pressure levels, it is assumed that there are varying strong influences from other systems to these neurons. The fact that these neurons are influenced by cardiovascular afferents does not mean, however, that they are cardiovascular neurons exclusively. It is suggested that blood-pressure reticular neurons may belong to the cardiovascular system as well as to other brain stem systems."} {"id": "PMID:1276874", "title": "Metabolic regulations of the rhythmic activity in pacemaker neurons. III. Neutralization of the pentylenetetrazol effect in regularly beating Aplysia neurons by metabolic modifiers.", "content": "In regular beating pacemaker neurons isolated from the sea hare Aplysia californica, 30-50 mM pentylenetetrazol (PTZ) induces spike doublets and triplets, multi-spike bursts, and paroxysmal depolarizing shifts. The development of the characteristic PTZ-induced changes in impluse pattern is preceded by a transient increase in discharge frequency and a reduction in after-hyperpolarization. According to earlier findings, the rhythmic spike activity of pacemaker neurons is governed by a phosphofructokinase-fructose-1,6-diphosphatase-mediated substrate cycle, the activation of which leads to the appearance of spike bursts. Inhibitory modifiers of this neuronal substrate cycle, such as citrate, ATP, and 3-phosphoglycerate, are able to neutralize the changes in the impluse characteristics occurring as the result of PTZ action. Since the reinitiated single-spike trains reverted again to the PTZ pattern following the further addition of activating modifiers, such as fructose-1,6-diphosphate or fructose-6-phosphate, it appears likely that PTZ exerts an influence on the metabolic reactions driving the rhythmic spike activity. In contrast to the reversible effects of the metabolic modifiers the conventional anti-convulsants, phenobarbital and pentobarbital, merely block all spike activity.", "contents": "Metabolic regulations of the rhythmic activity in pacemaker neurons. III. Neutralization of the pentylenetetrazol effect in regularly beating Aplysia neurons by metabolic modifiers. In regular beating pacemaker neurons isolated from the sea hare Aplysia californica, 30-50 mM pentylenetetrazol (PTZ) induces spike doublets and triplets, multi-spike bursts, and paroxysmal depolarizing shifts. The development of the characteristic PTZ-induced changes in impluse pattern is preceded by a transient increase in discharge frequency and a reduction in after-hyperpolarization. According to earlier findings, the rhythmic spike activity of pacemaker neurons is governed by a phosphofructokinase-fructose-1,6-diphosphatase-mediated substrate cycle, the activation of which leads to the appearance of spike bursts. Inhibitory modifiers of this neuronal substrate cycle, such as citrate, ATP, and 3-phosphoglycerate, are able to neutralize the changes in the impluse characteristics occurring as the result of PTZ action. Since the reinitiated single-spike trains reverted again to the PTZ pattern following the further addition of activating modifiers, such as fructose-1,6-diphosphate or fructose-6-phosphate, it appears likely that PTZ exerts an influence on the metabolic reactions driving the rhythmic spike activity. In contrast to the reversible effects of the metabolic modifiers the conventional anti-convulsants, phenobarbital and pentobarbital, merely block all spike activity."} {"id": "PMID:1276875", "title": "Eye movements evoked by superior colliculus stimulation in the alert cat.", "content": "(1) The electrical stimulation of the superior colliculus (SC) in the cat evokes exclusively conjugate and contraversive eye saccades. (2) Their maximum velocity is markedly higher than that of spontaneous saccades. (3) The stimulus parameters (intensity, frequency, pulse width) have but little effect on the characteristics of the saccades. (4) In the anterior half of the SC, corresponding to the projection of the 12-15 central degrees of the retina, amplitude and direction of saccades depend exclusively on the position of the electrode. (5) In the posterior half, corresponding to the projection of the peripheral retina, saccades are 'goal directed' and the position of the goal is determined by the location of the electrode. (6) An increase in stimulus train length produces, in the anterior part, a succession of identical saccades and, in the posterior part, a goal fixation. (7) Taking all these data into consideration, a model of the foveation process in the cat is proposed.", "contents": "Eye movements evoked by superior colliculus stimulation in the alert cat. (1) The electrical stimulation of the superior colliculus (SC) in the cat evokes exclusively conjugate and contraversive eye saccades. (2) Their maximum velocity is markedly higher than that of spontaneous saccades. (3) The stimulus parameters (intensity, frequency, pulse width) have but little effect on the characteristics of the saccades. (4) In the anterior half of the SC, corresponding to the projection of the 12-15 central degrees of the retina, amplitude and direction of saccades depend exclusively on the position of the electrode. (5) In the posterior half, corresponding to the projection of the peripheral retina, saccades are 'goal directed' and the position of the goal is determined by the location of the electrode. (6) An increase in stimulus train length produces, in the anterior part, a succession of identical saccades and, in the posterior part, a goal fixation. (7) Taking all these data into consideration, a model of the foveation process in the cat is proposed."} {"id": "PMID:1276882", "title": "Thermoregulatory responses to intraventricular norepinephrine in normal and hypothalamic-damaged rats.", "content": "We examined the effects of intraventricular injection of low doses of norepinephrine (NE) on internal temperature and on behavioral and reflexive thermoregulatory responses in unrestrained rats. NE lowered the body temperature of the rats in cold and neutral environments but had little effect in the heat. The hypothermia was blocked by alpha-adrenergic antagonists but unchanged by beta-adrenergic antagonists. In the cold, the hypothermia was caused primarily by a lowered metabolic rate. At ambient temperature 25 degrees C, it was caused primarily by vasodilatation while metabolic rate increased. Thus, reflexive responses were not integrated to lower body temperature. Behavioral responding compensated for the hypothermia. In the cold, rats increased responding to get heat after NE. In a warm environment, they did not increase responding to escape heat. Thus, both reflexive and behavioral results support the idea that the set-point is unchanged after intraventricular NE. Wherever in the brain the NE may be acting, it is not in the preoptic-anterior hypothalamic area, because when this area was ablated, the hypothermia in response to intraventricular NE was greatly exaggerated.", "contents": "Thermoregulatory responses to intraventricular norepinephrine in normal and hypothalamic-damaged rats. We examined the effects of intraventricular injection of low doses of norepinephrine (NE) on internal temperature and on behavioral and reflexive thermoregulatory responses in unrestrained rats. NE lowered the body temperature of the rats in cold and neutral environments but had little effect in the heat. The hypothermia was blocked by alpha-adrenergic antagonists but unchanged by beta-adrenergic antagonists. In the cold, the hypothermia was caused primarily by a lowered metabolic rate. At ambient temperature 25 degrees C, it was caused primarily by vasodilatation while metabolic rate increased. Thus, reflexive responses were not integrated to lower body temperature. Behavioral responding compensated for the hypothermia. In the cold, rats increased responding to get heat after NE. In a warm environment, they did not increase responding to escape heat. Thus, both reflexive and behavioral results support the idea that the set-point is unchanged after intraventricular NE. Wherever in the brain the NE may be acting, it is not in the preoptic-anterior hypothalamic area, because when this area was ablated, the hypothermia in response to intraventricular NE was greatly exaggerated."} {"id": "PMID:1276890", "title": "Striatal afferent connections in the turtle (Chrysemys picta) as revealed by retrograde axonal transport of horseradish peroxidase.", "content": "Horseradish peroxidase (HRP, 30% solution, 0.1-0.3 mul, 72 h) was injected unilaterally into the basal striatum (STR) and the dorsal ventricular ridge (DVR) of adult turtles (Chrysemys picta) in order to demonstrate the cells of origin of some afferents to these telencephalic structures. After selective STR injection, HRP-labeled cells were visualized in the dorsal thalamus and midbrain tegmentum, ipsilaterally. At thalamic level, HRP-positive neurons were located around nucleus rotundus, i.e., mainly within nuclei dorsomedialis anterior, dorsolateralis anterior and less abundantly in nuclei ventralis and reuniens. At midbrain level, a large population of labeled neurons was disclosed within the ventrolateral portion of rostral tegmentum. Other HRP-positive neuronal somata were found scattered throughout the lateral portion of the caudal midbrain tegmentum. In addition, labeled axons were visualized in both peduncles of the lateral forebrain bundle (LFB) after STR injection. The HRP-positive fibers of the dorsal peduncle of the LFB were followed up to the ipsilateral labeled thalamic cells where they appear to arise, whereas the HRP-containing axons of the ventral peduncle were traced down to the lateral midbrain tegmentum where they appear to arborize. Most of the HRP injections into the DVR were confined to the mediodorsal quadrant of the rostral half of the DVR. In such a case, a very large number of HRP-positive cells were disclosed within all thalamic nuclei surrounding nucleus rotundus, ipsilaterally. In addition, numerous labeled neurons were also found in nucleus rotundus itself and within nucleus reuniens. No HRP-positive cells were disclosed caudally to the meso-diencephalic junction after DVR injection.", "contents": "Striatal afferent connections in the turtle (Chrysemys picta) as revealed by retrograde axonal transport of horseradish peroxidase. Horseradish peroxidase (HRP, 30% solution, 0.1-0.3 mul, 72 h) was injected unilaterally into the basal striatum (STR) and the dorsal ventricular ridge (DVR) of adult turtles (Chrysemys picta) in order to demonstrate the cells of origin of some afferents to these telencephalic structures. After selective STR injection, HRP-labeled cells were visualized in the dorsal thalamus and midbrain tegmentum, ipsilaterally. At thalamic level, HRP-positive neurons were located around nucleus rotundus, i.e., mainly within nuclei dorsomedialis anterior, dorsolateralis anterior and less abundantly in nuclei ventralis and reuniens. At midbrain level, a large population of labeled neurons was disclosed within the ventrolateral portion of rostral tegmentum. Other HRP-positive neuronal somata were found scattered throughout the lateral portion of the caudal midbrain tegmentum. In addition, labeled axons were visualized in both peduncles of the lateral forebrain bundle (LFB) after STR injection. The HRP-positive fibers of the dorsal peduncle of the LFB were followed up to the ipsilateral labeled thalamic cells where they appear to arise, whereas the HRP-containing axons of the ventral peduncle were traced down to the lateral midbrain tegmentum where they appear to arborize. Most of the HRP injections into the DVR were confined to the mediodorsal quadrant of the rostral half of the DVR. In such a case, a very large number of HRP-positive cells were disclosed within all thalamic nuclei surrounding nucleus rotundus, ipsilaterally. In addition, numerous labeled neurons were also found in nucleus rotundus itself and within nucleus reuniens. No HRP-positive cells were disclosed caudally to the meso-diencephalic junction after DVR injection."} {"id": "PMID:1276891", "title": "The rodent neostriatum: a Golgi analysis.", "content": "In the adult rodent, coronal sections of Golgi impregnations of the neostriatum display a compact segregation of axon fascicles, neuronal clusters, and dendritic bundles thus forming an areolar configuration. Isolated neurons are rarely seen. The dorsomedial region of the neostriatum appears free of axon fascicles and dendritic bundles. Horizontal and sagittal sections of the neostriatum show clusters of cells parallel to axon fascicles. The neurons exhibit spine-laden dendrites with an initial spine-free segment. Neonatal impregnations exhibit a different configuration. Neonatally, cells tend to cluster but there is no bundling of dendrites. Neurons are spine-free or have protospines on the soma and the dendrites, including the initial segment. Transition from neonate to adult configuration is discernible at about 15 days after birth. The neostriatum of carnivores exhibits a different structure from the rodent neostriatum. This difference is associated with a developed anterior limb of the internal capsule in the carnivore. The axon fascicle-free portion of the carnivore neostriatum lacks dendritic bundles and pallisades. Portions near the capsule with axon fascicles appear similar to the rodent neostriatum with dendritic bundlings and pallisading. Such findings emphasize the importance of total neuronal configuration (neuronal-architectonics) in morphologic analyses.", "contents": "The rodent neostriatum: a Golgi analysis. In the adult rodent, coronal sections of Golgi impregnations of the neostriatum display a compact segregation of axon fascicles, neuronal clusters, and dendritic bundles thus forming an areolar configuration. Isolated neurons are rarely seen. The dorsomedial region of the neostriatum appears free of axon fascicles and dendritic bundles. Horizontal and sagittal sections of the neostriatum show clusters of cells parallel to axon fascicles. The neurons exhibit spine-laden dendrites with an initial spine-free segment. Neonatal impregnations exhibit a different configuration. Neonatally, cells tend to cluster but there is no bundling of dendrites. Neurons are spine-free or have protospines on the soma and the dendrites, including the initial segment. Transition from neonate to adult configuration is discernible at about 15 days after birth. The neostriatum of carnivores exhibits a different structure from the rodent neostriatum. This difference is associated with a developed anterior limb of the internal capsule in the carnivore. The axon fascicle-free portion of the carnivore neostriatum lacks dendritic bundles and pallisades. Portions near the capsule with axon fascicles appear similar to the rodent neostriatum with dendritic bundlings and pallisading. Such findings emphasize the importance of total neuronal configuration (neuronal-architectonics) in morphologic analyses."} {"id": "PMID:1276892", "title": "Trans-glial channel-facilitated translocation of tracer protein across ventral nerve root sheaths of crayfish.", "content": "Trans-glial channels, which traverse the multilamellate glial sheath of crayfish nerves, are easily recognized in freeze-fracture preparations. Their structure and position in the glial layers of the sheath strongly supports the suggestion that they serve to facilitate rapid movement of molecules and fluids from outside the sheath to the surface of axons contained within. Segments of ventral ganglion nerve roots, which were ligated at their free ends, were immersed in crayfish Ringer solution containing 10 mg/ml horseradish peroxidase (HRP). Electron microscopic examination of the nerve sheath 30 sec after exposure to peroxidase showed that the protein had passed across the sheath and was present near the axon surface. Reaction product was present in trans-glial channels as well as in extracellular clefts and adaxonal tubular lattices thereby supporting the notion that these structures constitute a specialized conduit traversing the sheath. Often, 'fronts' of reaction product were observed across the sheath from its exterior to the interior reflecting a gradual accumulation of protein in extracellular clefts toward the axon. After 5 min in HRP-Ringer, protein appeared in all channels, extracellular clefts, and tubular lattices. With increased length of exposure of ligated nerve segments to HRP-Ringer, reaction product was found in vesicles in glial cytoplasm adjacent to axons. Results from this study suggest that trans-glial channels constitute an efficient system for rapid solute movement across nerve sheaths and may represent a mechanism whereby ions and nutrients are made available to nerves isolated in an avascular sheath.", "contents": "Trans-glial channel-facilitated translocation of tracer protein across ventral nerve root sheaths of crayfish. Trans-glial channels, which traverse the multilamellate glial sheath of crayfish nerves, are easily recognized in freeze-fracture preparations. Their structure and position in the glial layers of the sheath strongly supports the suggestion that they serve to facilitate rapid movement of molecules and fluids from outside the sheath to the surface of axons contained within. Segments of ventral ganglion nerve roots, which were ligated at their free ends, were immersed in crayfish Ringer solution containing 10 mg/ml horseradish peroxidase (HRP). Electron microscopic examination of the nerve sheath 30 sec after exposure to peroxidase showed that the protein had passed across the sheath and was present near the axon surface. Reaction product was present in trans-glial channels as well as in extracellular clefts and adaxonal tubular lattices thereby supporting the notion that these structures constitute a specialized conduit traversing the sheath. Often, 'fronts' of reaction product were observed across the sheath from its exterior to the interior reflecting a gradual accumulation of protein in extracellular clefts toward the axon. After 5 min in HRP-Ringer, protein appeared in all channels, extracellular clefts, and tubular lattices. With increased length of exposure of ligated nerve segments to HRP-Ringer, reaction product was found in vesicles in glial cytoplasm adjacent to axons. Results from this study suggest that trans-glial channels constitute an efficient system for rapid solute movement across nerve sheaths and may represent a mechanism whereby ions and nutrients are made available to nerves isolated in an avascular sheath."} {"id": "PMID:1276893", "title": "The effect of subfornical organ lesions and ventricular blockade on drinking induced by angiotensin II.", "content": "The role of the subfornical organ (SFO) as the unique receptor site for the drinking behavior induced by intracranial injections of angiotensin II (AII) was investigated. It was found that: (1) drinking in response to intraventricular (IVT) injections of AII was reduced in 6 rats but was unchanged after 80-100% damage of the SFO in 4 cases; (2) reduction of drinking to lateral ventricular application of AII was seen with no apparent SFO damage in 4 rats; (3) recovery of the AII induced drinking deficit was consistently observed within a short time interval (14 days), even in those animals with complete SFO lesions: (4) the presence of ventricular debris was correlated with deficits in water intake to IVT angiotensin injections. In a second experiment artificial blockade of the ventricular space was produced by a plugging technique. Plugging the anterior third ventricle simulated the effects of SFO lesioning. It was concluded that the SFO is not a unique receptor area since the ventral anterior third ventricle is also sensitive for AII (IVT) induced drinking. If the SFO is a receptor site for AII circulating in the CSF it is probably not the only periventricular receptor site. Access of AII to the anterior ventral third ventricle appears to be essential for inducement of drinking.", "contents": "The effect of subfornical organ lesions and ventricular blockade on drinking induced by angiotensin II. The role of the subfornical organ (SFO) as the unique receptor site for the drinking behavior induced by intracranial injections of angiotensin II (AII) was investigated. It was found that: (1) drinking in response to intraventricular (IVT) injections of AII was reduced in 6 rats but was unchanged after 80-100% damage of the SFO in 4 cases; (2) reduction of drinking to lateral ventricular application of AII was seen with no apparent SFO damage in 4 rats; (3) recovery of the AII induced drinking deficit was consistently observed within a short time interval (14 days), even in those animals with complete SFO lesions: (4) the presence of ventricular debris was correlated with deficits in water intake to IVT angiotensin injections. In a second experiment artificial blockade of the ventricular space was produced by a plugging technique. Plugging the anterior third ventricle simulated the effects of SFO lesioning. It was concluded that the SFO is not a unique receptor area since the ventral anterior third ventricle is also sensitive for AII (IVT) induced drinking. If the SFO is a receptor site for AII circulating in the CSF it is probably not the only periventricular receptor site. Access of AII to the anterior ventral third ventricle appears to be essential for inducement of drinking."} {"id": "PMID:1276894", "title": "Activity, avoidance learning and regional 5-hydroxytryptamine following intra-brain stem 5,7-dihydroxytryptamine and electrolytic midbrain raphe lesions in the rat.", "content": "Rats underwent one of the following treatments: (1) electrocoagulation of both the dorsal and median midbrain raphe nuclei; (2) 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) injection (10 mug, as the salt, in 5 mul vehicle) into the vicinity of each midbrain raphe nucleus; (3) intra-brain stem vehicle (5 mul of 0.2% ascorbic acid in isotonic saline) injections; or, (4) a control operation. Open field activity and one-way avoidance conditioning were examined on postoperative days 16-23. Regional central 5-hydroxytryptamine (5-HT) and catecholamine (CA) concentrations were determined 25-27 days postoperatively. Regional 5-HT levels were greatly reduced following 5,7-DHT administration and electrolytic raphe lesions. The 5,7-DHT rats also showed a reduction in spinal 5-HT content. Central CA concentrations were not affected. Variation in the pattern of regional 5-HT changes after 5,7-DHT treatment was observed but appeared to be related to the adequacy of the dorsal raphe (B7) injection. Only the electrolytic raphe lesion animals, however, showed increased locomotor activity and retarded acquisition and forced-extinction of the one-way avoidance response. In contrast, no significant differences were observed in the open field and avoidance behavior of the 5,7-DHT, vehicle, and control groups. The hyperactivity and impaired one-way avoidance performance observed after electrolytic midbrain raphe lesions are not related simply to reductions in regional forebrain 5-HT and may well be due to damage of non-serotonergic neural systems. Clearly, the behavioral effects of central 5-HT depletion depend on the method employed. The role of 5-HT in regulating activity level and mediating avoidance behavior, furthermore, remains to be determined.", "contents": "Activity, avoidance learning and regional 5-hydroxytryptamine following intra-brain stem 5,7-dihydroxytryptamine and electrolytic midbrain raphe lesions in the rat. Rats underwent one of the following treatments: (1) electrocoagulation of both the dorsal and median midbrain raphe nuclei; (2) 5,7-dihydroxytryptamine creatinine sulfate (5,7-DHT) injection (10 mug, as the salt, in 5 mul vehicle) into the vicinity of each midbrain raphe nucleus; (3) intra-brain stem vehicle (5 mul of 0.2% ascorbic acid in isotonic saline) injections; or, (4) a control operation. Open field activity and one-way avoidance conditioning were examined on postoperative days 16-23. Regional central 5-hydroxytryptamine (5-HT) and catecholamine (CA) concentrations were determined 25-27 days postoperatively. Regional 5-HT levels were greatly reduced following 5,7-DHT administration and electrolytic raphe lesions. The 5,7-DHT rats also showed a reduction in spinal 5-HT content. Central CA concentrations were not affected. Variation in the pattern of regional 5-HT changes after 5,7-DHT treatment was observed but appeared to be related to the adequacy of the dorsal raphe (B7) injection. Only the electrolytic raphe lesion animals, however, showed increased locomotor activity and retarded acquisition and forced-extinction of the one-way avoidance response. In contrast, no significant differences were observed in the open field and avoidance behavior of the 5,7-DHT, vehicle, and control groups. The hyperactivity and impaired one-way avoidance performance observed after electrolytic midbrain raphe lesions are not related simply to reductions in regional forebrain 5-HT and may well be due to damage of non-serotonergic neural systems. Clearly, the behavioral effects of central 5-HT depletion depend on the method employed. The role of 5-HT in regulating activity level and mediating avoidance behavior, furthermore, remains to be determined."} {"id": "PMID:1276895", "title": "[The Schmidt-Lantermann incisures of the myelin sheath of Mauthner axons: site of longitudinal myelin growth].", "content": "The myelin sheath of the Mauthner axons in the spinal cord of young and adult fish belonging to the family Cyprinidae was examined by phase and electron microscopy. The sheath thickened considerably with age, the number of lamellae increasing from 200-230 in young fish (length 2--4 cm) to 250-300 in adult animals (length 20-25 cm). During this growth, the myelin sheath remained fairly compact and of optimal thickness for impulse propagation, the axon/fiber thickness ratio being 0.67-0.72 in young and 0.76-0.78 in adult fish. As already observed by previous investigators, the Mauthner axons lacked nodes of Ranvier. However, Schmidt-Lantermann's clefts (SLC) were present at irregular intervals. Within the SLC, parallel arranged osmiophilic bands of variable length and with a thickness of approx. 42-44 nm were observed to form a transitional zone between the cytoplasmic areas of the oligodendrocyte and the typical myelin structure. Between such adjacent 'D-bands', which thinned out to build up the major dense lines, an electron translucent area measuring approx. 25--26 nm in width contained a thin 'I-band' (8--10 nm) which was continuous with the intraperiod line. It is speculated that, in the Mauthner axon, the SLCs may be sites where freshly synthesized myelin is added to the lamellae already present, thus permitting their longitudinal growth.", "contents": "[The Schmidt-Lantermann incisures of the myelin sheath of Mauthner axons: site of longitudinal myelin growth]. The myelin sheath of the Mauthner axons in the spinal cord of young and adult fish belonging to the family Cyprinidae was examined by phase and electron microscopy. The sheath thickened considerably with age, the number of lamellae increasing from 200-230 in young fish (length 2--4 cm) to 250-300 in adult animals (length 20-25 cm). During this growth, the myelin sheath remained fairly compact and of optimal thickness for impulse propagation, the axon/fiber thickness ratio being 0.67-0.72 in young and 0.76-0.78 in adult fish. As already observed by previous investigators, the Mauthner axons lacked nodes of Ranvier. However, Schmidt-Lantermann's clefts (SLC) were present at irregular intervals. Within the SLC, parallel arranged osmiophilic bands of variable length and with a thickness of approx. 42-44 nm were observed to form a transitional zone between the cytoplasmic areas of the oligodendrocyte and the typical myelin structure. Between such adjacent 'D-bands', which thinned out to build up the major dense lines, an electron translucent area measuring approx. 25--26 nm in width contained a thin 'I-band' (8--10 nm) which was continuous with the intraperiod line. It is speculated that, in the Mauthner axon, the SLCs may be sites where freshly synthesized myelin is added to the lamellae already present, thus permitting their longitudinal growth."} {"id": "PMID:1276896", "title": "Ultrastructural changes in the developing nucleolus following axotomy.", "content": "A large, basophilic, Feulgen-negative structure has been observed within the nucleoli of golden hamster facial motor neurons. This 'intranucleolar body' was seen, at the electron microscopic level, to be composed of granules which are thought to be ribonucleoprotein particles. At 15 days postnatal age, this aggregation of granules had not yet be appeared. However, by 20--24 days, a small intranucleolar body had developed. At maturity, the intranucleolar body had a diameter of up to 2 mum. Facial nerve axotomy at 15 days did not appreciably alter the nucleolar morphology at 19 days; neither control (opposite side) nor experimental nucleoli contained intranucleolar bodies. Normal nucleoli developed intranucleolar bodies, however, between the ages of 20 and 24 days. After axotomy at 20 days and sacrifice at 24 days, a comparison of facial neuronal nucleoli demonstrated that while an intranucleolar body formed in the control, axotomy prevented this structure from forming at its normal time. Also, when the facial nerve of an adult hamster was axotomized and observed 4 days postoperatively, an intact intranucleolar body was not seen. Instead, the granular portions of the nucleolus appeared to have been dispersed into several small aggregates. We believe that the changes observed in granule distribution, both with development and after axotomy, are morphological indications of a qualitative and/or a quantitative change in rRNA synthesis.", "contents": "Ultrastructural changes in the developing nucleolus following axotomy. A large, basophilic, Feulgen-negative structure has been observed within the nucleoli of golden hamster facial motor neurons. This 'intranucleolar body' was seen, at the electron microscopic level, to be composed of granules which are thought to be ribonucleoprotein particles. At 15 days postnatal age, this aggregation of granules had not yet be appeared. However, by 20--24 days, a small intranucleolar body had developed. At maturity, the intranucleolar body had a diameter of up to 2 mum. Facial nerve axotomy at 15 days did not appreciably alter the nucleolar morphology at 19 days; neither control (opposite side) nor experimental nucleoli contained intranucleolar bodies. Normal nucleoli developed intranucleolar bodies, however, between the ages of 20 and 24 days. After axotomy at 20 days and sacrifice at 24 days, a comparison of facial neuronal nucleoli demonstrated that while an intranucleolar body formed in the control, axotomy prevented this structure from forming at its normal time. Also, when the facial nerve of an adult hamster was axotomized and observed 4 days postoperatively, an intact intranucleolar body was not seen. Instead, the granular portions of the nucleolus appeared to have been dispersed into several small aggregates. We believe that the changes observed in granule distribution, both with development and after axotomy, are morphological indications of a qualitative and/or a quantitative change in rRNA synthesis."} {"id": "PMID:1276897", "title": "Type 1 and 2 synaptic junctions: differences in distribution of concanavalin A binding sites and stability of the junctional adhesion.", "content": "Two classes of synaptosomes have been distinguished in subcellular fractions from rat forebrain. They differ in morphology and distribution of concanavalin A binding sites. Morphological examination suggests that the two classes correspond to the type 1 (excitatory) and type 2 (inhibitory) synapses of intact brain tissue. Under the conditions of incubation employed in this study, type 1 synaptosomes show splitting of the synaptic junctions, but the type 2 junctions are apparently stable. The chemical differences illustrated by the differences in concanavalin A binding sites suggest that type 1 and type 2 synaptic junctions differ fundamentally in supramolecular structure rather than being superficial variants of basically similar structures.", "contents": "Type 1 and 2 synaptic junctions: differences in distribution of concanavalin A binding sites and stability of the junctional adhesion. Two classes of synaptosomes have been distinguished in subcellular fractions from rat forebrain. They differ in morphology and distribution of concanavalin A binding sites. Morphological examination suggests that the two classes correspond to the type 1 (excitatory) and type 2 (inhibitory) synapses of intact brain tissue. Under the conditions of incubation employed in this study, type 1 synaptosomes show splitting of the synaptic junctions, but the type 2 junctions are apparently stable. The chemical differences illustrated by the differences in concanavalin A binding sites suggest that type 1 and type 2 synaptic junctions differ fundamentally in supramolecular structure rather than being superficial variants of basically similar structures."} {"id": "PMID:1276898", "title": "Electrophysiological study on the postnatal development of neuronal mechanisms in the rat cerebellar cortex.", "content": "(1) Functional commencements of the neuronal elements in the cerebellar cortex of young rats were studied electrophysiologically by means of laminar field potential analyses in the cortex on stimulation of the cerebellar surface (Loc) and the white matter (WM). (2) The antidromic action potential of Purkinje cells on the WM stimulation was observed at one day after birth. The climbing fiber excitation of Purkinje cells on the stimulation was noted at 3 days after birth. (3) The mossy fiber-granule cell synapses were found to function at 10 days after birth and the Golgi cell inhibition of granule cells could be proved at the same time. The excitatory action of parallel fibers and the inhibitory action of basket-stellate cells on Purkinje cells appeared simultaneously at about 12 days after birth. The transverse distribution across the cerebellar folium of the basket-stellate cell inhibitory action on Purkinje cells was found to be narrow up to 60 days after birth. (4) These results concerning the dates of commencement of excitatory and inhibitory synaptic actions in the cerebellar cortex were compared with those of synaptogenesis studied morphologically, and some implications of the dates in the functional development of the cerebellar cortex were discussed.", "contents": "Electrophysiological study on the postnatal development of neuronal mechanisms in the rat cerebellar cortex. (1) Functional commencements of the neuronal elements in the cerebellar cortex of young rats were studied electrophysiologically by means of laminar field potential analyses in the cortex on stimulation of the cerebellar surface (Loc) and the white matter (WM). (2) The antidromic action potential of Purkinje cells on the WM stimulation was observed at one day after birth. The climbing fiber excitation of Purkinje cells on the stimulation was noted at 3 days after birth. (3) The mossy fiber-granule cell synapses were found to function at 10 days after birth and the Golgi cell inhibition of granule cells could be proved at the same time. The excitatory action of parallel fibers and the inhibitory action of basket-stellate cells on Purkinje cells appeared simultaneously at about 12 days after birth. The transverse distribution across the cerebellar folium of the basket-stellate cell inhibitory action on Purkinje cells was found to be narrow up to 60 days after birth. (4) These results concerning the dates of commencement of excitatory and inhibitory synaptic actions in the cerebellar cortex were compared with those of synaptogenesis studied morphologically, and some implications of the dates in the functional development of the cerebellar cortex were discussed."} {"id": "PMID:1276899", "title": "Visual receptive field types in the nucleus dorsolateralis anterior of the pigeon's thalamus.", "content": "Extracellular recordings were made from cells in the dorsolateral thalamus (DLLv, DLLd, DLAmc) of the pigeon, and their receptive field properties analyzed with stationary and moving visual stimuli. One hundred and ten cells were classified as follows on the basis of their responses. I. On-center and off-center cells (56%). Most of the units in this class had a powerful inhibitory surround which decreased the activity generated at the field center and in some cases gave rise to firing when stimulated alone. II. On-off center cells (16%). These gave on-off responses to static stimulation. More than half of them had an inhibitory surround which suppressed both on and off discharge, or in other cases either the on or the off burst of the center response. This group of cells also responded strongly to motion independently of direction. III. Cells sensitive only to motion (28%). The discharges to movements of units in this class were not affected by the direction of motion. The visual properties of the thalamic units are discussed in conjunction with previous results in the optic tectum of the pigeon.", "contents": "Visual receptive field types in the nucleus dorsolateralis anterior of the pigeon's thalamus. Extracellular recordings were made from cells in the dorsolateral thalamus (DLLv, DLLd, DLAmc) of the pigeon, and their receptive field properties analyzed with stationary and moving visual stimuli. One hundred and ten cells were classified as follows on the basis of their responses. I. On-center and off-center cells (56%). Most of the units in this class had a powerful inhibitory surround which decreased the activity generated at the field center and in some cases gave rise to firing when stimulated alone. II. On-off center cells (16%). These gave on-off responses to static stimulation. More than half of them had an inhibitory surround which suppressed both on and off discharge, or in other cases either the on or the off burst of the center response. This group of cells also responded strongly to motion independently of direction. III. Cells sensitive only to motion (28%). The discharges to movements of units in this class were not affected by the direction of motion. The visual properties of the thalamic units are discussed in conjunction with previous results in the optic tectum of the pigeon."} {"id": "PMID:1276900", "title": "Differential effects of brain lesions on thirst induced by the administration of angiotensin-II to the preoptic region, subfornical organ and anterior third ventricle.", "content": "(1) The possibility that water intake elicited by the administration of angiotensin-II to the preoptic region (POA), subfornical organ and anterior third ventricle is mediated by separate neural systems was investigated in 58 male Wistar rats using electrolytic lesion techniques. (2) Lesions of the midlateral hypothalamus and paramedial rostral midbrain produced a significant reduction in water intake to angiotensin-II microinjected into the POA but did not affect drinking following administration of angiotensin-II to the subfornical organ or anterior third ventricle. (3) Ablation of the midlateral hypothalamus, paramedial rostral midbrain, habenular nucleus or interpeduncular nucleus had no significant effect on water intake elicited in response to microinjection of carbachol or hypertonic saline into the preoptic region, subfornical organ or anterior third ventricle. (4) In a second series of 12 animals lesions of the subfornical organ attenuated water intake in response to a peripheral injection of renin or isoproteronol without disrupting drinking to peripheral administration of hypertonic saline or polyethylene glycol or to 24 h water deprivation. (5) It is concluded that separate neural systems mediate water intake elicited by administration of angiotensin-II to the preoptic area, subfornical organ and anterior third ventricle. The possible physiological significance of independent and parallel peripheral and cerebral renin-angiotensin systems for the control of drinking behavior mediated by angiotensin-II is discussed. (6) The present results are in agreement with previous work which indicates that water intake induced by central administration of angiotensin-II, carbachol and hypertonic saline is subserved by different neural substrates.", "contents": "Differential effects of brain lesions on thirst induced by the administration of angiotensin-II to the preoptic region, subfornical organ and anterior third ventricle. (1) The possibility that water intake elicited by the administration of angiotensin-II to the preoptic region (POA), subfornical organ and anterior third ventricle is mediated by separate neural systems was investigated in 58 male Wistar rats using electrolytic lesion techniques. (2) Lesions of the midlateral hypothalamus and paramedial rostral midbrain produced a significant reduction in water intake to angiotensin-II microinjected into the POA but did not affect drinking following administration of angiotensin-II to the subfornical organ or anterior third ventricle. (3) Ablation of the midlateral hypothalamus, paramedial rostral midbrain, habenular nucleus or interpeduncular nucleus had no significant effect on water intake elicited in response to microinjection of carbachol or hypertonic saline into the preoptic region, subfornical organ or anterior third ventricle. (4) In a second series of 12 animals lesions of the subfornical organ attenuated water intake in response to a peripheral injection of renin or isoproteronol without disrupting drinking to peripheral administration of hypertonic saline or polyethylene glycol or to 24 h water deprivation. (5) It is concluded that separate neural systems mediate water intake elicited by administration of angiotensin-II to the preoptic area, subfornical organ and anterior third ventricle. The possible physiological significance of independent and parallel peripheral and cerebral renin-angiotensin systems for the control of drinking behavior mediated by angiotensin-II is discussed. (6) The present results are in agreement with previous work which indicates that water intake induced by central administration of angiotensin-II, carbachol and hypertonic saline is subserved by different neural substrates."} {"id": "PMID:1276901", "title": "The projections of the A8, A9 and A10 dopaminergic cell bodies: evidence for a nigral-hypothalamic-median eminence dopaminergic pathway.", "content": "Using the microdissection method of Palkovits and a sensitive microassay for dopamine (DA) and norepinephrine (NE), the CNS projections of the nigral A8, A9 and A10 dopaminergic cell bodies have been determined in rat brain. Following bilateral electrolytic lesions of the A8-A9-A10 region, DA levels fell significantly in the following areas: dorsal septal nucleus (85%), olfactory tubercle (75%), lateral amygdaloid nucleus (75%), habenula (75%), parietal cortex (75%), cingulate cortex (70%), cerebellum (50%), thalamic paraventricular nucleus (50%), and preoptic suprachiasmatic nucleus (45%). Of particular interest was the finding of a 40% fall in the dopamine levels of the median eminence after such lesions. Concentrations of NE in these same areas following lesions of the A8-A9-A10 region were unchanged. These findings suggest that the nigral A8, A9 and A10 dopaminergic cell bodies, project diffusely to many different areas of cortex, hypothalamus, and brain stem, and, more importantly, provide evidence for a previously unsuspected dopaminergic pathway from substantia nigra to median eminence, an area intimately concerned with neuroendocrine regulation.", "contents": "The projections of the A8, A9 and A10 dopaminergic cell bodies: evidence for a nigral-hypothalamic-median eminence dopaminergic pathway. Using the microdissection method of Palkovits and a sensitive microassay for dopamine (DA) and norepinephrine (NE), the CNS projections of the nigral A8, A9 and A10 dopaminergic cell bodies have been determined in rat brain. Following bilateral electrolytic lesions of the A8-A9-A10 region, DA levels fell significantly in the following areas: dorsal septal nucleus (85%), olfactory tubercle (75%), lateral amygdaloid nucleus (75%), habenula (75%), parietal cortex (75%), cingulate cortex (70%), cerebellum (50%), thalamic paraventricular nucleus (50%), and preoptic suprachiasmatic nucleus (45%). Of particular interest was the finding of a 40% fall in the dopamine levels of the median eminence after such lesions. Concentrations of NE in these same areas following lesions of the A8-A9-A10 region were unchanged. These findings suggest that the nigral A8, A9 and A10 dopaminergic cell bodies, project diffusely to many different areas of cortex, hypothalamus, and brain stem, and, more importantly, provide evidence for a previously unsuspected dopaminergic pathway from substantia nigra to median eminence, an area intimately concerned with neuroendocrine regulation."} {"id": "PMID:1276902", "title": "Distribution of glutamate decarboxylase in discrete brain nuclei.", "content": "The L-glutamate decarboxylase (GAD) levels of 70 rat brain nuclei were determined. The distribution of GAD is uneven. High AAD activity was found in the substantia nigra, the colliculi, some hypothalamic nuclei (e.g. dorsomedial) some nuclei of the limbic system (e.g. tractus diagonalis and accumbens) and the medial forebrain bundle. The reticular part of the substantia nigra had the highest activity, two-fold higher than any other nucleus. Low GAD activity was found in the nuclei of the pons, the hypothalamic median eminence and the reticular formation. Moderate activity was measured in most areas studied. The biochemical mapping of GAD is discussed in relation to possible GABA pathways in the brain.", "contents": "Distribution of glutamate decarboxylase in discrete brain nuclei. The L-glutamate decarboxylase (GAD) levels of 70 rat brain nuclei were determined. The distribution of GAD is uneven. High AAD activity was found in the substantia nigra, the colliculi, some hypothalamic nuclei (e.g. dorsomedial) some nuclei of the limbic system (e.g. tractus diagonalis and accumbens) and the medial forebrain bundle. The reticular part of the substantia nigra had the highest activity, two-fold higher than any other nucleus. Low GAD activity was found in the nuclei of the pons, the hypothalamic median eminence and the reticular formation. Moderate activity was measured in most areas studied. The biochemical mapping of GAD is discussed in relation to possible GABA pathways in the brain."} {"id": "PMID:1276905", "title": "The application of network analysis to the study of branching patterns of large dendritic fields.", "content": "Network analysis of dendritic fields not only defines the topology and connectivity of segments of an arborescence, but offers a means of discovering how networks grow. An important theory has recently been formulated29 suggesting that dendritic branching patterns may be established by synaptogenic interaction of dendritic growth cones with growing axons. This thesis may be verified through network analysis since the theory predicts that growth at pendant vertices will predominate in dendritic networks, that dendritic growth will be directed into areas of maximal synaptogenic activity and that arc lengths will be inversely related, and the order of branching at vertices directly related, to the magnitude of the synaptogenic activity operating about growing dendritic terminals. The possibility of a preponderance of terminal growth may be detected by comparing the topologies in an observed dendritic network with those of a series of hypothetical growth models. This paper provides the frequency table for models grown by monochotomous, dichotomous and trichotomous branching on random pendant vertices and random arcs for large networks in which 'set theory' contingencies are included. The paper also describes a method of calculating branching probabilities from the measurement of segment lengths, which is a means of testing the last mentioned prediction of the synaptogenic theory of denddritic growth. The method of network analysis is then discussed in relation to probable dendritic growth patterns, the constancy of segment lengths and the interaction of extrinsic and intrinsic factors in determining branching probabilities.", "contents": "The application of network analysis to the study of branching patterns of large dendritic fields. Network analysis of dendritic fields not only defines the topology and connectivity of segments of an arborescence, but offers a means of discovering how networks grow. An important theory has recently been formulated29 suggesting that dendritic branching patterns may be established by synaptogenic interaction of dendritic growth cones with growing axons. This thesis may be verified through network analysis since the theory predicts that growth at pendant vertices will predominate in dendritic networks, that dendritic growth will be directed into areas of maximal synaptogenic activity and that arc lengths will be inversely related, and the order of branching at vertices directly related, to the magnitude of the synaptogenic activity operating about growing dendritic terminals. The possibility of a preponderance of terminal growth may be detected by comparing the topologies in an observed dendritic network with those of a series of hypothetical growth models. This paper provides the frequency table for models grown by monochotomous, dichotomous and trichotomous branching on random pendant vertices and random arcs for large networks in which 'set theory' contingencies are included. The paper also describes a method of calculating branching probabilities from the measurement of segment lengths, which is a means of testing the last mentioned prediction of the synaptogenic theory of denddritic growth. The method of network analysis is then discussed in relation to probable dendritic growth patterns, the constancy of segment lengths and the interaction of extrinsic and intrinsic factors in determining branching probabilities."} {"id": "PMID:1276906", "title": "The effects of reduced climbing and parallel fibre input on Purkinje cell dendritic growth.", "content": "The effects of afferent fibre depletion on the development of the dendritic trees of Purkinje cells in the cerbellum were investigated. Parallel fibres were reduced by postnatal administration of a schedule of low level X-irradiation. Climbing fibers were prevented from innervating the cerebellum by lesioning the olivo-cerebellar tract. Network analysis was performed on Purkinje cells in Golgi-Cox preparations of the vermis of 30-day-old animals. tin the irradiated cerebella Purkinje cells with a 'weeping willow' type morphology predominated. Purkinje cells devoid of their climbing fibre contact exhibited large spines on their main dendritic trunks. In both experimental situations the size of the dendritic tree was reduced. This diminution was the result of a decrease in the total number of dendritic segemnts. Individual segment lengths were largely unalteral. Topological type analysis revealed that the trees had arisen in a manner indistinguishable from terminal dichotomous branching and that the 'weep-willow' pattern was produced by a deviation of branching from a purely random form. The interaction of intrinsic and extrinsic factors in the formation of segments and on the nature of branching were discussed.", "contents": "The effects of reduced climbing and parallel fibre input on Purkinje cell dendritic growth. The effects of afferent fibre depletion on the development of the dendritic trees of Purkinje cells in the cerbellum were investigated. Parallel fibres were reduced by postnatal administration of a schedule of low level X-irradiation. Climbing fibers were prevented from innervating the cerebellum by lesioning the olivo-cerebellar tract. Network analysis was performed on Purkinje cells in Golgi-Cox preparations of the vermis of 30-day-old animals. tin the irradiated cerebella Purkinje cells with a 'weeping willow' type morphology predominated. Purkinje cells devoid of their climbing fibre contact exhibited large spines on their main dendritic trunks. In both experimental situations the size of the dendritic tree was reduced. This diminution was the result of a decrease in the total number of dendritic segemnts. Individual segment lengths were largely unalteral. Topological type analysis revealed that the trees had arisen in a manner indistinguishable from terminal dichotomous branching and that the 'weep-willow' pattern was produced by a deviation of branching from a purely random form. The interaction of intrinsic and extrinsic factors in the formation of segments and on the nature of branching were discussed."} {"id": "PMID:1276912", "title": "Effects of one-stage or serial transections of the lateral olfactory tracts on behavior and plasma testosterone levels in male hamsters.", "content": "Bilateral transections of the later olfactory (LOT) in male hamsters at the rostral border of the olfactory tubercle or anterior to the tubercle produced severe deficits in mounting, scent marking, food hoarding and nesting behaviors. There were no impairments of these behaviors following unilateral transections. Cutting of the LOT in two stages, and provision of additional experience in sexual and territorial behaviors during the interval between the first and second transection, did not alleviate the behavioral deficits. Impairments in mounting and scent marking were dissociated in some subjects, indicating individual differences in the hamsters' dependence on chemosensory cues for the regulation of these two types of social behavior. It is suggested that the apparent sparing of behavioral function which has been associated with gradual destruction of nervous tissue is due to the development of alternate mechanisms of response to environmental cues, and may be more difficult when brain damage is in structures which initially process these cues. Although sexual and territorial behaviors in the hamster are dependent on gonadal hormones, the observed impairments of these behaviors could not be explained as indirect consequences of lesion effects on the hypophysiogonadal axis. Circulating testosterone (T) levels in experimental subjects were not different from levels in control (sham-operated) subjects. An inverse correlation was observed between the control subjects' circulating T levels and their incidence of scent marking. A similar correlation was observed between postoperative T levels and preoperative marking rates in experimental subjects, despite the fact that most subjects failed to scent mark after bilateral LOT transections. The latter observation strengthens the inference that the bilateral deficits were independent of changes in basal hormone levels.", "contents": "Effects of one-stage or serial transections of the lateral olfactory tracts on behavior and plasma testosterone levels in male hamsters. Bilateral transections of the later olfactory (LOT) in male hamsters at the rostral border of the olfactory tubercle or anterior to the tubercle produced severe deficits in mounting, scent marking, food hoarding and nesting behaviors. There were no impairments of these behaviors following unilateral transections. Cutting of the LOT in two stages, and provision of additional experience in sexual and territorial behaviors during the interval between the first and second transection, did not alleviate the behavioral deficits. Impairments in mounting and scent marking were dissociated in some subjects, indicating individual differences in the hamsters' dependence on chemosensory cues for the regulation of these two types of social behavior. It is suggested that the apparent sparing of behavioral function which has been associated with gradual destruction of nervous tissue is due to the development of alternate mechanisms of response to environmental cues, and may be more difficult when brain damage is in structures which initially process these cues. Although sexual and territorial behaviors in the hamster are dependent on gonadal hormones, the observed impairments of these behaviors could not be explained as indirect consequences of lesion effects on the hypophysiogonadal axis. Circulating testosterone (T) levels in experimental subjects were not different from levels in control (sham-operated) subjects. An inverse correlation was observed between the control subjects' circulating T levels and their incidence of scent marking. A similar correlation was observed between postoperative T levels and preoperative marking rates in experimental subjects, despite the fact that most subjects failed to scent mark after bilateral LOT transections. The latter observation strengthens the inference that the bilateral deficits were independent of changes in basal hormone levels."} {"id": "PMID:1276913", "title": "A primitive gigantopyramidal field buried in the depth of the cingulate sulcus of the human brain.", "content": "By stereomicroscopical examination of a complete series of pigment preparations up to 1000 mum thick, a gigantopyramidal area in the brain of man is described, which lies in front of the primary motor field on the medial surface of the hemisphere and is almost totally buried in the depth of the cingulate sulcus extending in both length and width over about 15 mm. Serial sections cut in the transverse plane display the field approximately within the limits of the commissura anterior on the one hand and the corpora mamillaria on the other, where it occupies large parts of the dorsal wall of the gyrus cinguli (lower bank of sulcus cinguli) and a small area of the adjacent superior frontal gyrus. The sharply outlined field does not fuse with the primary motor area and is evidently more primitively organized than the precentral motor field. Structural details betray an intimate relationship between this gigantopyramidal field and the archipallial proisocortex. We could clearly trace a gradation, that is, a stepwise change of architectonic features in constant orientation from the limbic proisocortex over a small paralimbic transition zone to the gigantopyramidal field, accounting for the numerous limbic traits recognizable within it, such as, for instance, an accentuated external granular layer, a dense and broad lamina pyramidalis, and a band-like appearance of Va.", "contents": "A primitive gigantopyramidal field buried in the depth of the cingulate sulcus of the human brain. By stereomicroscopical examination of a complete series of pigment preparations up to 1000 mum thick, a gigantopyramidal area in the brain of man is described, which lies in front of the primary motor field on the medial surface of the hemisphere and is almost totally buried in the depth of the cingulate sulcus extending in both length and width over about 15 mm. Serial sections cut in the transverse plane display the field approximately within the limits of the commissura anterior on the one hand and the corpora mamillaria on the other, where it occupies large parts of the dorsal wall of the gyrus cinguli (lower bank of sulcus cinguli) and a small area of the adjacent superior frontal gyrus. The sharply outlined field does not fuse with the primary motor area and is evidently more primitively organized than the precentral motor field. Structural details betray an intimate relationship between this gigantopyramidal field and the archipallial proisocortex. We could clearly trace a gradation, that is, a stepwise change of architectonic features in constant orientation from the limbic proisocortex over a small paralimbic transition zone to the gigantopyramidal field, accounting for the numerous limbic traits recognizable within it, such as, for instance, an accentuated external granular layer, a dense and broad lamina pyramidalis, and a band-like appearance of Va."} {"id": "PMID:1276914", "title": "Retinofugal pathways in normal and albino axolotls.", "content": "The retinofugal pathways of normal and albino axolotls have been studied by tracing the transport of radioactive materials after tritiated proline was injected into one eye. The pathways demonstrated by this method include crossed projections to the diencephalon, pretectum, and tectum, and a small component that goes to the midbrain tegmentum in the basal optic root. Ipsilaterally, radioactive label was found in all of the same cerebral regions, but in much smaller quantities. Although on the basis of earlier fiber degeneration studies most of the label could be interpreted as evidence for direct retinofugal pathways, some of the label, especially that in the ipsilateral tectum, does not correspond to a known pathway and may represent a small new component or have been produced by transneuronal transport mechanisms. The pattern of labeling was the same in the albino as in the normally pigmented axolotls. Thus, it appears that the abnormality of the chiasmatic pathway, which has been found in albinos of many different mammalian species, does not occur in axolotls.", "contents": "Retinofugal pathways in normal and albino axolotls. The retinofugal pathways of normal and albino axolotls have been studied by tracing the transport of radioactive materials after tritiated proline was injected into one eye. The pathways demonstrated by this method include crossed projections to the diencephalon, pretectum, and tectum, and a small component that goes to the midbrain tegmentum in the basal optic root. Ipsilaterally, radioactive label was found in all of the same cerebral regions, but in much smaller quantities. Although on the basis of earlier fiber degeneration studies most of the label could be interpreted as evidence for direct retinofugal pathways, some of the label, especially that in the ipsilateral tectum, does not correspond to a known pathway and may represent a small new component or have been produced by transneuronal transport mechanisms. The pattern of labeling was the same in the albino as in the normally pigmented axolotls. Thus, it appears that the abnormality of the chiasmatic pathway, which has been found in albinos of many different mammalian species, does not occur in axolotls."} {"id": "PMID:1276915", "title": "Influence of hippocampectomy on gastric ulcer in rats.", "content": "Hippocampectomized male rats were prepared, and the incidence as well as severity of gastric ulceration upon restraint were compared with those of normal control animals and controls with localized damage to the cortex over the hippocampus. In another experiment, observations on gastric ulceration were made without restraint in hippocampectomized animals, normal controls, controls with cortical damage, vagotomized animals and animals that received hippocampectomy as well as vagotomy. Both in restrained and unrestrained states, the incidence of animals with ulcer as well as the number and the total area of ulcers per stomach were significantly larger in the hippocampal animals than they were in the other animal groups. Vagotomy abolished the effect of hippocampectomy upon gastric ulceration in the unrestrained state. We infer that the hippocampus helps to protect the stomach from ulceration partly by controlling vagal activity.", "contents": "Influence of hippocampectomy on gastric ulcer in rats. Hippocampectomized male rats were prepared, and the incidence as well as severity of gastric ulceration upon restraint were compared with those of normal control animals and controls with localized damage to the cortex over the hippocampus. In another experiment, observations on gastric ulceration were made without restraint in hippocampectomized animals, normal controls, controls with cortical damage, vagotomized animals and animals that received hippocampectomy as well as vagotomy. Both in restrained and unrestrained states, the incidence of animals with ulcer as well as the number and the total area of ulcers per stomach were significantly larger in the hippocampal animals than they were in the other animal groups. Vagotomy abolished the effect of hippocampectomy upon gastric ulceration in the unrestrained state. We infer that the hippocampus helps to protect the stomach from ulceration partly by controlling vagal activity."} {"id": "PMID:1276916", "title": "Central generation of locomotion in the spinal dogfish.", "content": "After a transection of the spinal cord a dogfish performs continuous swimming movements with a phase lag between adjacent segments. It is shown that the intersegmental coordination remains after an extensive dorsal root transection as well as after curarization. In the former case the motor activity was recorded electromyographically in several segments along the body, in the latter case the intersegmental coordination was evaluated by recording the efferent activity in different ventral roots along the body. It was concluded that a spinal central network can account for the phase lag observed between successive segments during swimming. It was also shown that the efferent activity from parts of the spinal cord with no dorsal roots intact could be influenced by peripheral stimuli such as pressure on the pelvic fins; this result suggests that some afferent fibres reach the spinal cord via the ventral roots.", "contents": "Central generation of locomotion in the spinal dogfish. After a transection of the spinal cord a dogfish performs continuous swimming movements with a phase lag between adjacent segments. It is shown that the intersegmental coordination remains after an extensive dorsal root transection as well as after curarization. In the former case the motor activity was recorded electromyographically in several segments along the body, in the latter case the intersegmental coordination was evaluated by recording the efferent activity in different ventral roots along the body. It was concluded that a spinal central network can account for the phase lag observed between successive segments during swimming. It was also shown that the efferent activity from parts of the spinal cord with no dorsal roots intact could be influenced by peripheral stimuli such as pressure on the pelvic fins; this result suggests that some afferent fibres reach the spinal cord via the ventral roots."} {"id": "PMID:1276917", "title": "Glial cells and extracellular potassium: their relationship in mammalian cortex.", "content": "Simultaneous recordings were made of glial cell potentials and the extracellular potassium concentration ([K+]O) in cat cortex in an attempt to provide more quantitative information about the sensitivity of mammalian neuroglia to changes in [K+]O. A penicillin epileptogenic focus served to generate both transient and sustained elevations in [K+]O, thus allowing measurement of glial membrane potential (Vm) at both resting and increased [K+]O levels many times during the same experiment. Resting Vm averaged--92.6 +/- 10.9 mV for 33 glial cells. With each surface interictal spike, glial cells exhibited slow depolarizations averaging 18.4 +/- 6.5 mV which mirrored rises in [K+]O in many respects. Several discrepancies were found, however, between transient and focal rises in [K+]O and the associated glial cell depolarizations which made it difficult to determine accurately the effect of changes in [K+]O on glial Vm. For example, the amplitude of the glial depolarization caused by a single interictal discharge showed no constant relationship to depth below the cortical surface in contrast to the consistent laminar profile recorded by the K+ electrode. Thus, large glial membrane depolarizations could be recorded at times when there was little or no increase in measured [K+]O. Agreement between changes in [K+]O and glial cell depolarizations was closer to that predicted by the Nernst equation during sustained elevations in [K+]O such as occurred during ictal episodes ('seizures'). These findings may be related in part to methodology as a consequence of the different spatial relationships which exist between glial membrane, K+-electrode tip and released K+. In addition, though, they may indicate the presence of a functional glial syncytium.", "contents": "Glial cells and extracellular potassium: their relationship in mammalian cortex. Simultaneous recordings were made of glial cell potentials and the extracellular potassium concentration ([K+]O) in cat cortex in an attempt to provide more quantitative information about the sensitivity of mammalian neuroglia to changes in [K+]O. A penicillin epileptogenic focus served to generate both transient and sustained elevations in [K+]O, thus allowing measurement of glial membrane potential (Vm) at both resting and increased [K+]O levels many times during the same experiment. Resting Vm averaged--92.6 +/- 10.9 mV for 33 glial cells. With each surface interictal spike, glial cells exhibited slow depolarizations averaging 18.4 +/- 6.5 mV which mirrored rises in [K+]O in many respects. Several discrepancies were found, however, between transient and focal rises in [K+]O and the associated glial cell depolarizations which made it difficult to determine accurately the effect of changes in [K+]O on glial Vm. For example, the amplitude of the glial depolarization caused by a single interictal discharge showed no constant relationship to depth below the cortical surface in contrast to the consistent laminar profile recorded by the K+ electrode. Thus, large glial membrane depolarizations could be recorded at times when there was little or no increase in measured [K+]O. Agreement between changes in [K+]O and glial cell depolarizations was closer to that predicted by the Nernst equation during sustained elevations in [K+]O such as occurred during ictal episodes ('seizures'). These findings may be related in part to methodology as a consequence of the different spatial relationships which exist between glial membrane, K+-electrode tip and released K+. In addition, though, they may indicate the presence of a functional glial syncytium."} {"id": "PMID:1276918", "title": "Subcellular distribution of LDH isoenzymes in neuronal- and glial-enriched fractions.", "content": "The LDH isoenzymes of cell organelles (nuclei, mitochondria, microsomes, cytosol) obtained from neuronal- and glial-enriched fractions were determined by disc polyacrylamide electrophoresis and stained for enzyme activity. The quantitative estimation was made either by elution of isoenzymes or by densitometric measurements. The neuronal fraction was found to contain mainly H forms of LDH. The glial fraction also contained H forms but its M/H ratio was higher than that of the neuronal fraction. The cell organelles displayed some specificities with respect to the LDH isoenzymes distribution. The nuclei contained mainly M forms, the mitochondria H forms and the glial microsomal fraction M forms. It is suggested that the different LDH isoenzymes are related to the specific function of the different cell organelles.", "contents": "Subcellular distribution of LDH isoenzymes in neuronal- and glial-enriched fractions. The LDH isoenzymes of cell organelles (nuclei, mitochondria, microsomes, cytosol) obtained from neuronal- and glial-enriched fractions were determined by disc polyacrylamide electrophoresis and stained for enzyme activity. The quantitative estimation was made either by elution of isoenzymes or by densitometric measurements. The neuronal fraction was found to contain mainly H forms of LDH. The glial fraction also contained H forms but its M/H ratio was higher than that of the neuronal fraction. The cell organelles displayed some specificities with respect to the LDH isoenzymes distribution. The nuclei contained mainly M forms, the mitochondria H forms and the glial microsomal fraction M forms. It is suggested that the different LDH isoenzymes are related to the specific function of the different cell organelles."} {"id": "PMID:1276919", "title": "The uptake of delta9-tetrahydrocannabinol in choroid plexus and brain cortex in vitro and in vivo.", "content": "[3H]delta9 Tetrahydrocannabinol (delta9-THC) was actively transported by the choroid plexus and cerebral cortical slices of the rabbit when incubated as a BSA-microsuspension in artificial rabbit CSF. The transport system for delta9-THC in choroid plexus had a V max of 174 nmoles/mg tissue/h, approximately 9-fold greater than that observed for cortical slices. In vivo experiments demonstrated a preferential distribution of delta9-THC in choroid plexus at 1 h after intravenous injection. These results indicate that delta9-THC is actively accumulated by choroidal epithelium and may also be transported across the epithelial stroma into the capillary circulation. This suggests that the choroid plexus participates in the regulation of delta9-THC concentration in CSF and indirectly in brain by means of the \"sink\" function of the CSF.", "contents": "The uptake of delta9-tetrahydrocannabinol in choroid plexus and brain cortex in vitro and in vivo. [3H]delta9 Tetrahydrocannabinol (delta9-THC) was actively transported by the choroid plexus and cerebral cortical slices of the rabbit when incubated as a BSA-microsuspension in artificial rabbit CSF. The transport system for delta9-THC in choroid plexus had a V max of 174 nmoles/mg tissue/h, approximately 9-fold greater than that observed for cortical slices. In vivo experiments demonstrated a preferential distribution of delta9-THC in choroid plexus at 1 h after intravenous injection. These results indicate that delta9-THC is actively accumulated by choroidal epithelium and may also be transported across the epithelial stroma into the capillary circulation. This suggests that the choroid plexus participates in the regulation of delta9-THC concentration in CSF and indirectly in brain by means of the \"sink\" function of the CSF."} {"id": "PMID:1276920", "title": "Norepinephrine levels in traumatized spinal cord of catecholamine-depleted cats.", "content": "This study was designed to elucidate the origin of norepinephrine (NE) measured in spinal cord following trauma. In normal cats the NE concentration at the lesion site increased 63% over control 1 h following experimentally produced blunt trauma (400 g-cm). Spinal cords of adrenalectomized cats were also traumatized, but there was no increase in NE levels 1 h post-trauma. Spinal cord NE levels in these animals were not significantly different from normal or adrenalectomized non-injured controls. In the absence of one of the major peripheral sources of catecholamine, the adrenal medulla, our decreased NE levels prompt us to disagree with the hypothesis that NE measured in injured spinal cord is liberated from intrinsic neuronal systems. It is likely that the mechanism of NE accumulation is directly related to increased circulating levels of NE. The authors speculate on a possible reason for the conflicting results obtained by different laboratories in this area of research.", "contents": "Norepinephrine levels in traumatized spinal cord of catecholamine-depleted cats. This study was designed to elucidate the origin of norepinephrine (NE) measured in spinal cord following trauma. In normal cats the NE concentration at the lesion site increased 63% over control 1 h following experimentally produced blunt trauma (400 g-cm). Spinal cords of adrenalectomized cats were also traumatized, but there was no increase in NE levels 1 h post-trauma. Spinal cord NE levels in these animals were not significantly different from normal or adrenalectomized non-injured controls. In the absence of one of the major peripheral sources of catecholamine, the adrenal medulla, our decreased NE levels prompt us to disagree with the hypothesis that NE measured in injured spinal cord is liberated from intrinsic neuronal systems. It is likely that the mechanism of NE accumulation is directly related to increased circulating levels of NE. The authors speculate on a possible reason for the conflicting results obtained by different laboratories in this area of research."} {"id": "PMID:1276931", "title": "Possible relation between structure and spike shapes of neurones in guinea pig cochlear ganglion.", "content": "A two-component positive single unit spike could be recorded extracellularly from neurones in the acoustic ganglion of the guinea pig cochlea. Light and electron microscopy showed that the bipolar afferent neurones and their processes were myelinated except at nodes of Ranvier on either side of the cell soma, about 40 mum from the point of emergence of the myelinated processes. This anatomical finding and the properties of the two-component spike suggest that impulse conduction in these cells is achieved by rapid successive activation of the low threshold nodes on either side of the cell soma. The possible advantages of such a conduction system are discussed.", "contents": "Possible relation between structure and spike shapes of neurones in guinea pig cochlear ganglion. A two-component positive single unit spike could be recorded extracellularly from neurones in the acoustic ganglion of the guinea pig cochlea. Light and electron microscopy showed that the bipolar afferent neurones and their processes were myelinated except at nodes of Ranvier on either side of the cell soma, about 40 mum from the point of emergence of the myelinated processes. This anatomical finding and the properties of the two-component spike suggest that impulse conduction in these cells is achieved by rapid successive activation of the low threshold nodes on either side of the cell soma. The possible advantages of such a conduction system are discussed."} {"id": "PMID:1276932", "title": "The effect of activation history on tension production by individual muscle units.", "content": "Isometric responses of individual gastrocnemius muscle units of both fast (F) and slow (S) twitch type were studied during repetitive intracellular stimulation of the innervating motoneurons in anesthetized cats. Paired stimuli usually produced maximum responses (measured in terms of tension-time area) with interpulse intervals between 5 and 10 msec. However, longer pulse trains produced maximum tension-time area per pulse with relatively long interpulse intervals (referred to as the optimum interval). For each unit, stimulus intervals around the optimum produced maximum modulation of tension during unfused tetani. Post-activation potentiation produced shifts in the optimum toward longer intervals. The optimum intervals for type F units were shorter (mean 49.4 msec) than those for type S units (mean 86.9 msec), but there was no difference between the groups when the mean intervals were expressed in ratio with the twitch contraction time, Tc (F units: 1.42 X Tc; S units: 1.31 X Tc). The range of optimum intervals for all gastrocnemius muscle units corresponded to motoneuron firing frequencies of 7-40 pulses/sec, well within the frequency ranges observed for gastrocnemius motoneurons firing under natural synaptic drive. Insertion of a single short interval (5--10 msec) at the onset of a relatively low frequency stimulus train produced a prolonged 'catch-like' enhancement of tension output, particularly in type S units. The duration of the catch-like effect depended on the interval between pulses in the underlying basic train, and was maximum for intervals between 1 and 2 X Tc. The catch-like effect was also seen in type F units but its duration was curtailed by another process called the 'sag' property. The 'sag' property occurred in type F units over a wide range of stimulus intervals (usually 0.5-3 X Tc) but was present in type S units only with relatively long intervals (greater than 2 X Tc). The 'sag' property appears to represent a disenhancement process intrinsic to muscle unit fibers activated in unfused tetani.", "contents": "The effect of activation history on tension production by individual muscle units. Isometric responses of individual gastrocnemius muscle units of both fast (F) and slow (S) twitch type were studied during repetitive intracellular stimulation of the innervating motoneurons in anesthetized cats. Paired stimuli usually produced maximum responses (measured in terms of tension-time area) with interpulse intervals between 5 and 10 msec. However, longer pulse trains produced maximum tension-time area per pulse with relatively long interpulse intervals (referred to as the optimum interval). For each unit, stimulus intervals around the optimum produced maximum modulation of tension during unfused tetani. Post-activation potentiation produced shifts in the optimum toward longer intervals. The optimum intervals for type F units were shorter (mean 49.4 msec) than those for type S units (mean 86.9 msec), but there was no difference between the groups when the mean intervals were expressed in ratio with the twitch contraction time, Tc (F units: 1.42 X Tc; S units: 1.31 X Tc). The range of optimum intervals for all gastrocnemius muscle units corresponded to motoneuron firing frequencies of 7-40 pulses/sec, well within the frequency ranges observed for gastrocnemius motoneurons firing under natural synaptic drive. Insertion of a single short interval (5--10 msec) at the onset of a relatively low frequency stimulus train produced a prolonged 'catch-like' enhancement of tension output, particularly in type S units. The duration of the catch-like effect depended on the interval between pulses in the underlying basic train, and was maximum for intervals between 1 and 2 X Tc. The catch-like effect was also seen in type F units but its duration was curtailed by another process called the 'sag' property. The 'sag' property occurred in type F units over a wide range of stimulus intervals (usually 0.5-3 X Tc) but was present in type S units only with relatively long intervals (greater than 2 X Tc). The 'sag' property appears to represent a disenhancement process intrinsic to muscle unit fibers activated in unfused tetani."} {"id": "PMID:1276933", "title": "Specific angiotensin II receptive neurons in the cat subfornical organ.", "content": "To test if neurons in the subfornical organ (SFO) are specifically sensitive to angiotensin II (AII) we have applied the AII analog sar1-ala8-AII (P113) directly on to cells in the SFO by microiontophoresis. Adult cats were anesthetized and the SFO exposed for penetration by a 5-barreled micropipette electrode. Of 22 units which responded positively to AII, 7 were also positive to acetylcholine. P113 alone produced either no effect or a decrease in unit firing. P113 plus AII produced antagonism in 17 of 18 units. P113 plus acetylcholine produced antagonistic effects in 5 of 14 cases. Only two units were completely antagonized and 5 units showed agonistic interaction. The most sensitive antagonism with respect to dose of P113 was on neurons responsive only to AII and not to both AII and acetylcholine. We conclude that there are specific AII neurons in the SFO.", "contents": "Specific angiotensin II receptive neurons in the cat subfornical organ. To test if neurons in the subfornical organ (SFO) are specifically sensitive to angiotensin II (AII) we have applied the AII analog sar1-ala8-AII (P113) directly on to cells in the SFO by microiontophoresis. Adult cats were anesthetized and the SFO exposed for penetration by a 5-barreled micropipette electrode. Of 22 units which responded positively to AII, 7 were also positive to acetylcholine. P113 alone produced either no effect or a decrease in unit firing. P113 plus AII produced antagonism in 17 of 18 units. P113 plus acetylcholine produced antagonistic effects in 5 of 14 cases. Only two units were completely antagonized and 5 units showed agonistic interaction. The most sensitive antagonism with respect to dose of P113 was on neurons responsive only to AII and not to both AII and acetylcholine. We conclude that there are specific AII neurons in the SFO."} {"id": "PMID:1276934", "title": "Evidence for sar1-ala8-angiotensin crossing the blood cerebrospinal fluid barrier to antagonize central effects of angiotensin II.", "content": "Injections of angiotensin II into the cerebral ventricles of the rat produces both a drinking and a pressor response. We have measured both responses simultaneously in conscious animals. The effect of saralasin acetate (P113), a specific angiotensin II competitive antagonist, has been studied on these angiotensin II induced responses. The results show that: (1) P113 given intravenously (i.v.) in doses of 500 ng/min or 1800 ng/min has no observable effect on 50 ng angiotensin given intraventricularly (IVT). At 72 mug/min, however, there was a 55% reduction in the drinking and pressor responses to 50 ng angiotensin II (IVT); (2) 500 ng of P113 given IVT abolished the effects of 50 ng angiotensin II also given IVT and (3) P113 given i.v. at all doses antagonized the pressor effects of angiotensin II (i.v.) responses. The data indicate that both the drinking and pressor responses to angiotensin II (IVT) injections are centrally mediated and show that when a high enough dose of P113 is given peripherally the central effects of angiotensin II can be reduced. This suggests that a fraction of the P113 injected i.v. may pass across the blood-CSF barrier. Since P113 has a similar structure to angiotensin II the results have implications for studies in which high peripheral doses of angiotensin II are used.", "contents": "Evidence for sar1-ala8-angiotensin crossing the blood cerebrospinal fluid barrier to antagonize central effects of angiotensin II. Injections of angiotensin II into the cerebral ventricles of the rat produces both a drinking and a pressor response. We have measured both responses simultaneously in conscious animals. The effect of saralasin acetate (P113), a specific angiotensin II competitive antagonist, has been studied on these angiotensin II induced responses. The results show that: (1) P113 given intravenously (i.v.) in doses of 500 ng/min or 1800 ng/min has no observable effect on 50 ng angiotensin given intraventricularly (IVT). At 72 mug/min, however, there was a 55% reduction in the drinking and pressor responses to 50 ng angiotensin II (IVT); (2) 500 ng of P113 given IVT abolished the effects of 50 ng angiotensin II also given IVT and (3) P113 given i.v. at all doses antagonized the pressor effects of angiotensin II (i.v.) responses. The data indicate that both the drinking and pressor responses to angiotensin II (IVT) injections are centrally mediated and show that when a high enough dose of P113 is given peripherally the central effects of angiotensin II can be reduced. This suggests that a fraction of the P113 injected i.v. may pass across the blood-CSF barrier. Since P113 has a similar structure to angiotensin II the results have implications for studies in which high peripheral doses of angiotensin II are used."} {"id": "PMID:1276935", "title": "Effects of glutamate and sulphur containing amino acids on ammonia toxicity and methionine sulphoximine convulsions in mice.", "content": "Arginine and large doses of glutamate (greater than 500 mg/kg) were found to reduce ammonia toxicity transiently in mice. Smaller doses of glutamate (greater than or equal to 200 mg/kg) were effective when administered with glucose. Cysteic acid, homocysteine and methionine, but not taurine reduced ammonia toxicity. All 4 amino acids reduced the number of convulsions induced by methionine sulphoximine. It is proposed that taurine has a general anticonvulsant action and that cysteic acid, homocysteine and methionine may have a specific effect on the action of ammonia on the central nervous system.", "contents": "Effects of glutamate and sulphur containing amino acids on ammonia toxicity and methionine sulphoximine convulsions in mice. Arginine and large doses of glutamate (greater than 500 mg/kg) were found to reduce ammonia toxicity transiently in mice. Smaller doses of glutamate (greater than or equal to 200 mg/kg) were effective when administered with glucose. Cysteic acid, homocysteine and methionine, but not taurine reduced ammonia toxicity. All 4 amino acids reduced the number of convulsions induced by methionine sulphoximine. It is proposed that taurine has a general anticonvulsant action and that cysteic acid, homocysteine and methionine may have a specific effect on the action of ammonia on the central nervous system."} {"id": "PMID:1276942", "title": "Cerebellar corticonuclear projection in the cat. The vermis of the anterior and posterior lobes.", "content": "The projection of the vermis of the anterior and posterior lobes of the cerebellum to the fastigial nucleus was studied. It was attempted to obtain lesions restricted to the lobules and this was achieved for the posterior lobe only. The extent of lesions and of additional encroachments were determined by mapping degenerated descending cortical fibers in serial sections. Evidence was obtained that the projection of the vermis is restricted to the fastigial nucleus, without a contribution to the interposed nuclei, in the posterior lobe. Indirect evidence supports the existence of a similar arrangement in the anterior lobe. The projection appears to be distributed ipsilaterally. There is a topographical distribution of the cortical lobules in the different regions of the fastigial nucleus: each lobule projects to the nearest region of the nucleus. There is a divergence of the terminal ramifications of the axons originating from a given lobule within their area of termination. There is also an overlap between the borders of adjacent termination sites. It is concluded that there is a sequential representation of the cerebellar cortex in the fastigial nucleus.", "contents": "Cerebellar corticonuclear projection in the cat. The vermis of the anterior and posterior lobes. The projection of the vermis of the anterior and posterior lobes of the cerebellum to the fastigial nucleus was studied. It was attempted to obtain lesions restricted to the lobules and this was achieved for the posterior lobe only. The extent of lesions and of additional encroachments were determined by mapping degenerated descending cortical fibers in serial sections. Evidence was obtained that the projection of the vermis is restricted to the fastigial nucleus, without a contribution to the interposed nuclei, in the posterior lobe. Indirect evidence supports the existence of a similar arrangement in the anterior lobe. The projection appears to be distributed ipsilaterally. There is a topographical distribution of the cortical lobules in the different regions of the fastigial nucleus: each lobule projects to the nearest region of the nucleus. There is a divergence of the terminal ramifications of the axons originating from a given lobule within their area of termination. There is also an overlap between the borders of adjacent termination sites. It is concluded that there is a sequential representation of the cerebellar cortex in the fastigial nucleus."} {"id": "PMID:1276943", "title": "On glutaminase activity in mammalian synaptosomes.", "content": "A large proportion (30%) of tissue glutaminase activity was found localized in synaptosome fractions as well as purified mitochondrial fractions, where it is also enriched on a protein basis (2-fold). Sulphate was more effective (2-8-fold) than phosphate or chloride in activating the enzyme at concentrations above 10-12 mM, but equivalent to phosphate at lower concentrations (1-3 mM). At CSF levels (0.5 mM), glutamine is readily used by synaptosomes as a substrate in the presence of 10 mM glucose. It constitutes at least 50% to the carbon of aspartate, glutamate and GABA. Pool sizes of these amino acids are maintained in the presence of glutamine and glucose at CSF levels, but not by glucose alone. Ammonium ion at 1 mM substantially (30%) inhibits glutaminase utilisation by synaptosomes. It is suggested that CSF glutamine is a major substrate for the nerve ending in situ.", "contents": "On glutaminase activity in mammalian synaptosomes. A large proportion (30%) of tissue glutaminase activity was found localized in synaptosome fractions as well as purified mitochondrial fractions, where it is also enriched on a protein basis (2-fold). Sulphate was more effective (2-8-fold) than phosphate or chloride in activating the enzyme at concentrations above 10-12 mM, but equivalent to phosphate at lower concentrations (1-3 mM). At CSF levels (0.5 mM), glutamine is readily used by synaptosomes as a substrate in the presence of 10 mM glucose. It constitutes at least 50% to the carbon of aspartate, glutamate and GABA. Pool sizes of these amino acids are maintained in the presence of glutamine and glucose at CSF levels, but not by glucose alone. Ammonium ion at 1 mM substantially (30%) inhibits glutaminase utilisation by synaptosomes. It is suggested that CSF glutamine is a major substrate for the nerve ending in situ."} {"id": "PMID:1276944", "title": "Relative cerebral glucose uptake of neuronal perikarya and neuropil determined with 2-deoxyglucose in resting and swimming rat.", "content": "An autoradiographic method using tracer amounts of [14C]-2-deoxy-D-glucose (2-DG) was used to detect areas of the brain in which glucose consumption was altered in swimming as compared to resting rats. Areas in which changes occurred in the swimming rat were widespread in gray matter, being greatest in the cerebellar vermis and least in portions of the cerebellar hemispheres and the inferior colliculi. Improved resolution was obtained with an autoradiographic method for [3H]-2-DG. The number of grains per unit area over neuronal perikarya was either slightly greater or equal to that over the immediately surrounding neuropil in both resting and swimming rats. This indicated that the glucose consumption of neuronal perikarya and the immediately surrounding neuropil per unit volume were similar. Since gray matter is composed predominantly of neuropil, the present results indicate that the bulk of the total brain gray matter glucose consumption is accounted for by neuropil in both the resting and swimming states.", "contents": "Relative cerebral glucose uptake of neuronal perikarya and neuropil determined with 2-deoxyglucose in resting and swimming rat. An autoradiographic method using tracer amounts of [14C]-2-deoxy-D-glucose (2-DG) was used to detect areas of the brain in which glucose consumption was altered in swimming as compared to resting rats. Areas in which changes occurred in the swimming rat were widespread in gray matter, being greatest in the cerebellar vermis and least in portions of the cerebellar hemispheres and the inferior colliculi. Improved resolution was obtained with an autoradiographic method for [3H]-2-DG. The number of grains per unit area over neuronal perikarya was either slightly greater or equal to that over the immediately surrounding neuropil in both resting and swimming rats. This indicated that the glucose consumption of neuronal perikarya and the immediately surrounding neuropil per unit volume were similar. Since gray matter is composed predominantly of neuropil, the present results indicate that the bulk of the total brain gray matter glucose consumption is accounted for by neuropil in both the resting and swimming states."} {"id": "PMID:1276945", "title": "Rotation induced increases of glucose uptake in rat vestibular nuclei and vestibulocerebellum.", "content": "A new technique for the autoradiographic measurement of regional cerebral glucose consumption using tracer amounts of radioactive 2-deoxyglucose (2-DG) was employed to study the effects of vestibular inputs on local cerebral glucose metabolism. Rats rotated in the vertical plane showed localized increases of glucose utilization in the vestibular nuclei and several areas of the cerebellum: flocculus, nodulus, ventral uvula, and accessory paraflocculus. The changes in the cerebellum occurred both in the neuronal perikarya-rich granular layer and the neuropil-rich molecular layer. Differential changes resulting from rotation occurred within the granular layer of the nodulus, where at least 7 separate longitudinal zones of differing glucose consumption were seen. This type of longitudinal organization has been described previously in other areas of the vermis with other techniques.", "contents": "Rotation induced increases of glucose uptake in rat vestibular nuclei and vestibulocerebellum. A new technique for the autoradiographic measurement of regional cerebral glucose consumption using tracer amounts of radioactive 2-deoxyglucose (2-DG) was employed to study the effects of vestibular inputs on local cerebral glucose metabolism. Rats rotated in the vertical plane showed localized increases of glucose utilization in the vestibular nuclei and several areas of the cerebellum: flocculus, nodulus, ventral uvula, and accessory paraflocculus. The changes in the cerebellum occurred both in the neuronal perikarya-rich granular layer and the neuropil-rich molecular layer. Differential changes resulting from rotation occurred within the granular layer of the nodulus, where at least 7 separate longitudinal zones of differing glucose consumption were seen. This type of longitudinal organization has been described previously in other areas of the vermis with other techniques."} {"id": "PMID:1276951", "title": "Changes in the distribution of the dentate gyrus associational system following unilateral or bilateral entorhinal lesions in the adult rat.", "content": "The distribution of the dentate gyrus associational system was analyzed in naive adult rats and in those with either unilateral or bilateral lesions of the entorhinal cortex. Horseradish peroxidase histochemistry was used to trace the origin and course of this intrinsic fiber system. The fibers originated in the CA3-4 pyramidal cell field, apparently medial to the origin of the Schaffer collateral system, and followed a trajectory which was essentially identical to that described for this system by Zimmer36. The associational terminal field occupied the inner 26% of the dentate gyrus molecular layer in normal rats and 35-38% of the normal width of that layer following either ipsilateral or bilateral entorhinal lesion. These measurements are quite similar to those previously obtained on the commissural system terminal field in the normal and partially deafferented dentate gyrus. These results are interpreted to reflect axon sprouting by the associational fibers into the adjacent deafferented dendritic field.", "contents": "Changes in the distribution of the dentate gyrus associational system following unilateral or bilateral entorhinal lesions in the adult rat. The distribution of the dentate gyrus associational system was analyzed in naive adult rats and in those with either unilateral or bilateral lesions of the entorhinal cortex. Horseradish peroxidase histochemistry was used to trace the origin and course of this intrinsic fiber system. The fibers originated in the CA3-4 pyramidal cell field, apparently medial to the origin of the Schaffer collateral system, and followed a trajectory which was essentially identical to that described for this system by Zimmer36. The associational terminal field occupied the inner 26% of the dentate gyrus molecular layer in normal rats and 35-38% of the normal width of that layer following either ipsilateral or bilateral entorhinal lesion. These measurements are quite similar to those previously obtained on the commissural system terminal field in the normal and partially deafferented dentate gyrus. These results are interpreted to reflect axon sprouting by the associational fibers into the adjacent deafferented dendritic field."} {"id": "PMID:1276952", "title": "Evidence for the local synthesis of a transmitter enzyme (glutamic acid decarboxylase) in crayfish peripheral nerve.", "content": "The activities of three enzymes of neurotransmitter metabolism (choline acetyl-transferase, CAT; acetylcholinesterase, AChE; and glutamic acid decarboxylase, GAD) were studied in normal, transected, and organ cultured crayfish nerves. CAT (to a lesses extent AChE) was dramatically decreased in activity when the nerve was cut proximal to the nerve cell bodies. GAD activity was unaffected by such procedures. In organ cultured nerve, where both motor and sensory axons degenerated, the CAT and AChE activities were virtually absent, whereas GAD activity remained close to normal levels. Inhibition of protein synthesis in cultured nerve caused the GAD activity to decrease rapidly. In view of these data, and the well documented fact that motor axons survive axotomy whereas sensory axons do not, a hypothesis that GAD is synthesized in the peripheral nerve is presented.", "contents": "Evidence for the local synthesis of a transmitter enzyme (glutamic acid decarboxylase) in crayfish peripheral nerve. The activities of three enzymes of neurotransmitter metabolism (choline acetyl-transferase, CAT; acetylcholinesterase, AChE; and glutamic acid decarboxylase, GAD) were studied in normal, transected, and organ cultured crayfish nerves. CAT (to a lesses extent AChE) was dramatically decreased in activity when the nerve was cut proximal to the nerve cell bodies. GAD activity was unaffected by such procedures. In organ cultured nerve, where both motor and sensory axons degenerated, the CAT and AChE activities were virtually absent, whereas GAD activity remained close to normal levels. Inhibition of protein synthesis in cultured nerve caused the GAD activity to decrease rapidly. In view of these data, and the well documented fact that motor axons survive axotomy whereas sensory axons do not, a hypothesis that GAD is synthesized in the peripheral nerve is presented."} {"id": "PMID:1276967", "title": "The protein requirement of laying pullets with changing seasons in the tropics.", "content": "1. The protein requirements of White Leghorn laying pullets were evaluated in summer and winter using isocaloric diets containing 12-8, 15-0, 16-6, 18-5 and 21-6% protein. 2. The age at 50% production of summer-raised pullets was about 2 weeks later than that of winter-raised pullets irrespective of the concentration of dietary protein. 3. Egg production in summer-increased with increasing concentrations of protein up to 18-5%; further increases had no significant effect: in winter, egg production was similar provided the diet contained at least 15-0%. 4. The data on egg production, food consumption and egg weight indicated that the protein requirement of White Leghorn pullets is met by diets containing about 19% protein in summer and 15% in winter.", "contents": "The protein requirement of laying pullets with changing seasons in the tropics. 1. The protein requirements of White Leghorn laying pullets were evaluated in summer and winter using isocaloric diets containing 12-8, 15-0, 16-6, 18-5 and 21-6% protein. 2. The age at 50% production of summer-raised pullets was about 2 weeks later than that of winter-raised pullets irrespective of the concentration of dietary protein. 3. Egg production in summer-increased with increasing concentrations of protein up to 18-5%; further increases had no significant effect: in winter, egg production was similar provided the diet contained at least 15-0%. 4. The data on egg production, food consumption and egg weight indicated that the protein requirement of White Leghorn pullets is met by diets containing about 19% protein in summer and 15% in winter."} {"id": "PMID:1276968", "title": "Chick embryo heart rate during the last week of incubation: population studies.", "content": "1. A technique has been developed for the study of embryonic heart rate during the last week of incubation in a population of 84 embryos. 2. Heart rate is characteristic for a particular embryo but there are clear differences between individuals. 3. The population mean heart rate decreased from 262 beats/min at 14 d to a minimum of 250 beats/min at 19-5 d and then increased rapidly to more than 270 beats/min before hatching. 4. This pattern was repeatable and independent of the flock age. 5. Embryonic heart rate was also independent of egg size and hatching time. 6. The heart rate of male embryos was one to two beats/min lower than that of females.", "contents": "Chick embryo heart rate during the last week of incubation: population studies. 1. A technique has been developed for the study of embryonic heart rate during the last week of incubation in a population of 84 embryos. 2. Heart rate is characteristic for a particular embryo but there are clear differences between individuals. 3. The population mean heart rate decreased from 262 beats/min at 14 d to a minimum of 250 beats/min at 19-5 d and then increased rapidly to more than 270 beats/min before hatching. 4. This pattern was repeatable and independent of the flock age. 5. Embryonic heart rate was also independent of egg size and hatching time. 6. The heart rate of male embryos was one to two beats/min lower than that of females."} {"id": "PMID:1276969", "title": "Effects of different rates of inbreeding on the body weight and rate of gain of Japanese quail.", "content": "1. The effect of regular full-sib and double first cousin mating on body weight and rate of gain over six generations of Japanese quail was determined. 2. The depression of characters was more pronounced in the full-sib than in the double first cousin mating system, the relative depression due to parental inbreeding and offspring inbreeding depending on the magnitude of parental effect and individual's own genotypic effect on the character. 3. The body weight and rate of gain taken at an early age showed greater depression due to parental inbreeding whereas that taken near sexual maturity was depressed mainly due to individual's own inbreeding.", "contents": "Effects of different rates of inbreeding on the body weight and rate of gain of Japanese quail. 1. The effect of regular full-sib and double first cousin mating on body weight and rate of gain over six generations of Japanese quail was determined. 2. The depression of characters was more pronounced in the full-sib than in the double first cousin mating system, the relative depression due to parental inbreeding and offspring inbreeding depending on the magnitude of parental effect and individual's own genotypic effect on the character. 3. The body weight and rate of gain taken at an early age showed greater depression due to parental inbreeding whereas that taken near sexual maturity was depressed mainly due to individual's own inbreeding."} {"id": "PMID:1276970", "title": "Purification of p-hydroxyphenylpyruvate hydroxylase from rat liver--requirement for cofactors.", "content": "The enzyme p-hydroxyphenylpyruvate hydroxylase (EC 1.13.11.27) from rat liver was studied with the assay method which measures the release of 14CO2 from p-hydroxyphenyl [carboxy-14C]pyruvate. Extensive dialysis of the crude enzyme extract against Tris buffer or purification involving ammonium sulfate, gel filtration, and ion exchange results in loss of enzyme activity that can be reactivated by Fe2+, dichlorophenolindophenol, and various other agents. The effect of these activators depends critically on their final concentration in the assay media. A 70-fold purification of the enzyme fraction yielded a preparation which behaved as a single protein band in Sephadex G-150. It had an isoelectric point at 5.85 and molecular weight of 63 000. The enzyme obtained appears to be different in some respects from those described by other workers from the liver of dog, human, chicken, and frog.", "contents": "Purification of p-hydroxyphenylpyruvate hydroxylase from rat liver--requirement for cofactors. The enzyme p-hydroxyphenylpyruvate hydroxylase (EC 1.13.11.27) from rat liver was studied with the assay method which measures the release of 14CO2 from p-hydroxyphenyl [carboxy-14C]pyruvate. Extensive dialysis of the crude enzyme extract against Tris buffer or purification involving ammonium sulfate, gel filtration, and ion exchange results in loss of enzyme activity that can be reactivated by Fe2+, dichlorophenolindophenol, and various other agents. The effect of these activators depends critically on their final concentration in the assay media. A 70-fold purification of the enzyme fraction yielded a preparation which behaved as a single protein band in Sephadex G-150. It had an isoelectric point at 5.85 and molecular weight of 63 000. The enzyme obtained appears to be different in some respects from those described by other workers from the liver of dog, human, chicken, and frog."} {"id": "PMID:1276971", "title": "Studies related to antitumor antibiotics. Part VIII. Cleavage of DNA by streptonigrin analogues and the relationship to antineoplastic activity.", "content": "A group of substituted 5,8-quinolinequinones which exhibit antineoplastic activity and which are structurally related to the antitumor antibiotic streptonigrin induce single strand cleavage of PM2 covalently-closed circular-DNA (ccc-DNA) when reductively activated. The cleavage which is detected by an ethidium fluorescence assay is specifically enhanced by cuprous and ferrous ion and is selectively inhibited by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) and by free radical scavengers. Independent generation of the superoxide ion by xanthine-xanthine oxidase (EC 1.2.3.2) also cleaves PM2 DNA and therefore a chemical mechanism for the scission process induced by the streptonigrin analogues is formulated. A correlation between rate of PM2 ccc-DNA cleavage and inhibition of Walker carcinosarcoma 256 is observed.", "contents": "Studies related to antitumor antibiotics. Part VIII. Cleavage of DNA by streptonigrin analogues and the relationship to antineoplastic activity. A group of substituted 5,8-quinolinequinones which exhibit antineoplastic activity and which are structurally related to the antitumor antibiotic streptonigrin induce single strand cleavage of PM2 covalently-closed circular-DNA (ccc-DNA) when reductively activated. The cleavage which is detected by an ethidium fluorescence assay is specifically enhanced by cuprous and ferrous ion and is selectively inhibited by superoxide dismutase (EC 1.15.1.1) and catalase (EC 1.11.1.6) and by free radical scavengers. Independent generation of the superoxide ion by xanthine-xanthine oxidase (EC 1.2.3.2) also cleaves PM2 DNA and therefore a chemical mechanism for the scission process induced by the streptonigrin analogues is formulated. A correlation between rate of PM2 ccc-DNA cleavage and inhibition of Walker carcinosarcoma 256 is observed."} {"id": "PMID:1276972", "title": "Purification and properties of a carboxylesterase from the liver of tiger shark (Galeocerdo cuvier).", "content": "A procedure is described for the purification of a carboxylesterase from shark liver, using a chloroform-acetone powder prepared from the liver as the starting material. The yield of purified enzyme is approximately 50 mg from 530 g of chloroform-acetone powder. The preparation is electrophoretically homogeneous. Active-site titrations with paraoxon gave an equivalent weight of approximately 83 000. The molecular weight, found from sedimentation equilibrium experiments, is approximately 80 000. There is no evidence of any association or dissociation of this species. The enzyme shows a marked preference for aryl esters over alkyl esters, in contrast to other carboxylesterases so far studied. The amino acid composition of the purified enzyme is reported.", "contents": "Purification and properties of a carboxylesterase from the liver of tiger shark (Galeocerdo cuvier). A procedure is described for the purification of a carboxylesterase from shark liver, using a chloroform-acetone powder prepared from the liver as the starting material. The yield of purified enzyme is approximately 50 mg from 530 g of chloroform-acetone powder. The preparation is electrophoretically homogeneous. Active-site titrations with paraoxon gave an equivalent weight of approximately 83 000. The molecular weight, found from sedimentation equilibrium experiments, is approximately 80 000. There is no evidence of any association or dissociation of this species. The enzyme shows a marked preference for aryl esters over alkyl esters, in contrast to other carboxylesterases so far studied. The amino acid composition of the purified enzyme is reported."} {"id": "PMID:1276973", "title": "Identification of liver plasma membrane glycoproteins which bind to 125I-labelled concanavalin A following electrophoresis in sodium dodecyl sulfate.", "content": "Following electrophoresis of ovalbumin in sodium dodecyl sulfate (SDS) this glycoprotein bound 125I-labelled concanavalin A (Con A). The reaction was specific and proportional to the amount of glycoprotein present on the gel. This technique was used to study the Con-A-binding glycoproteins of liver cell surfaces. Mouse liver plasma membranes were purified and subfractionated to yield two fractions corresponding to the bile canalicular surface and the surface between adjacent hepatocytes (Evans, W.H. (1970) Biochem. J. 116, 833-842). Both fractions bound 125I-labelled Con A, the former binding two to three times more lectin than the latter. Following SDS gel electrophoresis individual membrane glycoproteins reacted with 125I-labelled Con A. Both membrane subfractions yielded qualitatively similar Con A binding profiles, seven binding proteins being present in each. The results are consistent with a generally uniform distribution of glycoproteins over the hepatocyte surface. The reaction of lectins with glycoproteins following SDS gel electrophoresis should find general application in the study of membrane composition.", "contents": "Identification of liver plasma membrane glycoproteins which bind to 125I-labelled concanavalin A following electrophoresis in sodium dodecyl sulfate. Following electrophoresis of ovalbumin in sodium dodecyl sulfate (SDS) this glycoprotein bound 125I-labelled concanavalin A (Con A). The reaction was specific and proportional to the amount of glycoprotein present on the gel. This technique was used to study the Con-A-binding glycoproteins of liver cell surfaces. Mouse liver plasma membranes were purified and subfractionated to yield two fractions corresponding to the bile canalicular surface and the surface between adjacent hepatocytes (Evans, W.H. (1970) Biochem. J. 116, 833-842). Both fractions bound 125I-labelled Con A, the former binding two to three times more lectin than the latter. Following SDS gel electrophoresis individual membrane glycoproteins reacted with 125I-labelled Con A. Both membrane subfractions yielded qualitatively similar Con A binding profiles, seven binding proteins being present in each. The results are consistent with a generally uniform distribution of glycoproteins over the hepatocyte surface. The reaction of lectins with glycoproteins following SDS gel electrophoresis should find general application in the study of membrane composition."} {"id": "PMID:1276974", "title": "Lipogenesis in muscle, liver, and adipose tissue of normal and dystrophic chickens.", "content": "The in vitro rate of oxidation and incorporation of [U-14C]glucose into lipids of muscle, liver, and adipose tissue of dystrophic and control chickens at 1 week, 1, 6, and 12 months of age were determined. The muscle and liver from dystrophic birds showed a high rate of [U-14C]glucose oxidation and incorporation into lipids during 1 week, 6 and 12 months. Insulin did not have any consistent stimulatory effect in all the tissues on the rate of glucose oxidation and incorporation into lipids. The contributory role played by the liver in the accumulation of lipids in dystrophic muscle is discussed.", "contents": "Lipogenesis in muscle, liver, and adipose tissue of normal and dystrophic chickens. The in vitro rate of oxidation and incorporation of [U-14C]glucose into lipids of muscle, liver, and adipose tissue of dystrophic and control chickens at 1 week, 1, 6, and 12 months of age were determined. The muscle and liver from dystrophic birds showed a high rate of [U-14C]glucose oxidation and incorporation into lipids during 1 week, 6 and 12 months. Insulin did not have any consistent stimulatory effect in all the tissues on the rate of glucose oxidation and incorporation into lipids. The contributory role played by the liver in the accumulation of lipids in dystrophic muscle is discussed."} {"id": "PMID:1276975", "title": "The synthesis and some pharmacological properties of (2-L-DOPA)-oxytocin.", "content": "The first reported synthetic analogue of a naturally occurring peptide with a residue of L-3,4-dihydroxyphenylalanine (L-DOPA) was prepared by coupling N-carbobenzoxy-S-benzylcysteinyl-L-DOPA azide with isoleucylglutaminylasparaginyl-S-benzylcysteinylprolylleuclglycinamide. The protecting groups were removed from the resultant nonapeptide derivative by sodium in liquid ammonia and the peptide analogue was formed by short term oxidation of the dithiol-containing compound. It was isolated by sequential partition chromatography and exclusion chromatography on Sephadex G-25. It was unstable at neutral or alkaline pH. [2-L-DOPA]-oxytocin was found to possess a minimum milk-ejection-like activity of 54 +/- 9 U/mg and uterotonic activity of 26 +/- 4 U/mg. These potencies are approximately 12% and 5% of the corresponding potencies of oxytocin.", "contents": "The synthesis and some pharmacological properties of (2-L-DOPA)-oxytocin. The first reported synthetic analogue of a naturally occurring peptide with a residue of L-3,4-dihydroxyphenylalanine (L-DOPA) was prepared by coupling N-carbobenzoxy-S-benzylcysteinyl-L-DOPA azide with isoleucylglutaminylasparaginyl-S-benzylcysteinylprolylleuclglycinamide. The protecting groups were removed from the resultant nonapeptide derivative by sodium in liquid ammonia and the peptide analogue was formed by short term oxidation of the dithiol-containing compound. It was isolated by sequential partition chromatography and exclusion chromatography on Sephadex G-25. It was unstable at neutral or alkaline pH. [2-L-DOPA]-oxytocin was found to possess a minimum milk-ejection-like activity of 54 +/- 9 U/mg and uterotonic activity of 26 +/- 4 U/mg. These potencies are approximately 12% and 5% of the corresponding potencies of oxytocin."} {"id": "PMID:1276976", "title": "Synthesis and some pharmacological properties of (2-tryptophan)-oxytocin.", "content": "Previous studies have suggested that an aromatic amino acid residue at position 2 in oxytocin facilitates the expression of the hormone's biolgocial activities. [2-Tryptophan]-oxytocin, in which a residue of tryptophan has replaced that of tyrosine in oxytocin, has been synthesized by the method of azide coupling of the N-terminal dipeptide and C-terminal heptapeptide amide. It was found to have approximately 0.1% of the potency of oxytocin in milk ejection and uterotonic biological activities.", "contents": "Synthesis and some pharmacological properties of (2-tryptophan)-oxytocin. Previous studies have suggested that an aromatic amino acid residue at position 2 in oxytocin facilitates the expression of the hormone's biolgocial activities. [2-Tryptophan]-oxytocin, in which a residue of tryptophan has replaced that of tyrosine in oxytocin, has been synthesized by the method of azide coupling of the N-terminal dipeptide and C-terminal heptapeptide amide. It was found to have approximately 0.1% of the potency of oxytocin in milk ejection and uterotonic biological activities."} {"id": "PMID:1276978", "title": "Sulfhydryl analogues of adenosine diphosphate: chemical synthesis and activity as platelet-aggregating agents.", "content": "2-Thioadenosine 5'-diphosphate (2-SH ADP), 2,2'-dithiobisadenosine 5'-diphosphate (2,2'-(S-ADP)2), 8-thioadenosine 5' diphosphate (8-SH ADP), and 6-mercaptopurine riboside 5'-disphosphate (6-MPRDP) were synthesized as potential affinity labels for ADP receptors on the blood-platelet membrane. The mean relative activities of these compounds in aggregating human platelets suspended in homologous plasma were 155% (2,2'-(S-ADP)2), 74% (2-SH ADP), 0.65% (8-SH ADP), and 0.08% (6-MPRDP). The mean relative activities against washed platelets were 249% (2,2\"-(S-ADP)2) and 115% (2-SH ADP), whereas no aggregation occurred with 8-SH ADP or 6-MPRDP. The last two compounds were found to be weak inhibitors of ADP-induced aggregation. Therefore, thio-substitution at postition 2 followed by oxidation to a disulfide appears to be the most promising approach to further studies of affinity labelling of membrane ADP-receptors.", "contents": "Sulfhydryl analogues of adenosine diphosphate: chemical synthesis and activity as platelet-aggregating agents. 2-Thioadenosine 5'-diphosphate (2-SH ADP), 2,2'-dithiobisadenosine 5'-diphosphate (2,2'-(S-ADP)2), 8-thioadenosine 5' diphosphate (8-SH ADP), and 6-mercaptopurine riboside 5'-disphosphate (6-MPRDP) were synthesized as potential affinity labels for ADP receptors on the blood-platelet membrane. The mean relative activities of these compounds in aggregating human platelets suspended in homologous plasma were 155% (2,2'-(S-ADP)2), 74% (2-SH ADP), 0.65% (8-SH ADP), and 0.08% (6-MPRDP). The mean relative activities against washed platelets were 249% (2,2\"-(S-ADP)2) and 115% (2-SH ADP), whereas no aggregation occurred with 8-SH ADP or 6-MPRDP. The last two compounds were found to be weak inhibitors of ADP-induced aggregation. Therefore, thio-substitution at postition 2 followed by oxidation to a disulfide appears to be the most promising approach to further studies of affinity labelling of membrane ADP-receptors."} {"id": "PMID:1276979", "title": "Pyruvate dehydrogenase activity in liver and brown fat of the developing rat.", "content": "The total activity of pyruvate dehydrogenase (EC 1.2.4.1) and the fraction of the enzyme in the active form were assayed in brown fat and liver throughout the development of the rat. In brown adipose tissue, the total activity increased until the late suckling period. After weaning, a decrease was noted. The fraction of the enzyme in the active form did not increase until after 10 days of age, reached its highest level in the late suckling period and remained at this level after weaning. Pyruvate dehydrogenase in liver decreased in both total activity and percentage activity in the early neonatal period. Both parameters increased after this period, reaching their highest levels in the late suckling period. In both fetal liver and fetal brown fat, the total activity of pyruvate dehydrogenase was increased by in vitro incubation with insulin.", "contents": "Pyruvate dehydrogenase activity in liver and brown fat of the developing rat. The total activity of pyruvate dehydrogenase (EC 1.2.4.1) and the fraction of the enzyme in the active form were assayed in brown fat and liver throughout the development of the rat. In brown adipose tissue, the total activity increased until the late suckling period. After weaning, a decrease was noted. The fraction of the enzyme in the active form did not increase until after 10 days of age, reached its highest level in the late suckling period and remained at this level after weaning. Pyruvate dehydrogenase in liver decreased in both total activity and percentage activity in the early neonatal period. Both parameters increased after this period, reaching their highest levels in the late suckling period. In both fetal liver and fetal brown fat, the total activity of pyruvate dehydrogenase was increased by in vitro incubation with insulin."} {"id": "PMID:1276980", "title": "The isolation and characterization of the tropomyosin binding component (TN-T) of bovine cardiac troponin.", "content": "The tropomyosin binding component (TN-T) of troponin was purified from bovine cardiac muscle using a combination of ion exchange chromatographies in the presence of urea. Sedimentation equilibrium experiments suggest a molecular weight for cardiac TN-T of 36 300 +/- 2 000, consistent with a value of 37 000 +/- 1 000 determining by polyacrylamide gel electrophoresis. Calculations based upon circular dichroism spectra indicate an apparent alpha-helical content of 43 +/- 3% for TN-T. Polyacrylamide gel electrophoresis and the effects of the calcium binding component (TN-C) upon the solubility of TN-T suggest that the two cardiac troponin components can interact with each other. Cosedimentation analysis of solutions containing cardiac tropomyosin and TN-T provide evidence for complex formation involving these two proteins. The data presented on the physical and chemical properties of TN-T, as well as the interaction studies indicate that the cardiac muscle regulatory system operates in a manner similar to that proposed for skeletal muscle.", "contents": "The isolation and characterization of the tropomyosin binding component (TN-T) of bovine cardiac troponin. The tropomyosin binding component (TN-T) of troponin was purified from bovine cardiac muscle using a combination of ion exchange chromatographies in the presence of urea. Sedimentation equilibrium experiments suggest a molecular weight for cardiac TN-T of 36 300 +/- 2 000, consistent with a value of 37 000 +/- 1 000 determining by polyacrylamide gel electrophoresis. Calculations based upon circular dichroism spectra indicate an apparent alpha-helical content of 43 +/- 3% for TN-T. Polyacrylamide gel electrophoresis and the effects of the calcium binding component (TN-C) upon the solubility of TN-T suggest that the two cardiac troponin components can interact with each other. Cosedimentation analysis of solutions containing cardiac tropomyosin and TN-T provide evidence for complex formation involving these two proteins. The data presented on the physical and chemical properties of TN-T, as well as the interaction studies indicate that the cardiac muscle regulatory system operates in a manner similar to that proposed for skeletal muscle."} {"id": "PMID:1276981", "title": "Properties of the citrate transporter in rat heart: implications for regulation of glycolysis by cytosolic citrate.", "content": "The efflux of [14C]citrate from rat heart mitochondria was significantly greater with L-malate as the extramitochondrial substrate as compared with [12C]citrate, isocitrate or phosphoenolpyruvate. The concentration of L-malate required for half-maximal rate of efflux of citrate was 0.45 mM and the maximum velocity was 0.36 nmol min-1 mg-1 mitochondrial protein at 23 degrees C. This citrate transporter was inhibited by 1,2,3-benzenetricarboxylate and palmitoyl-CoA but not to the same extent as these compounds inhibit the tricarboxylate carrier in rat liver mitochondria. The apparent inability of these mitochondria to transport citrate in the inward direction necessitates the presence of a cytosolic citrate removal pathway. We propose that the enzymes of this pathway in rat heart could be ATP citrate (pro-3S)-lyase (EC 4.1.3.a) and carnitine acetyltransferase (EC 2.3.1.7), both of which we demonstrate to have adequate activity in both the fed and fasted state. An hypothesis has been put forward to account for the inhibition of rat heart phosphofructokinase by citrate in the fasted state incorporating these properties of the citrate transporter and ATP citrate (pro-3S)-lyase.", "contents": "Properties of the citrate transporter in rat heart: implications for regulation of glycolysis by cytosolic citrate. The efflux of [14C]citrate from rat heart mitochondria was significantly greater with L-malate as the extramitochondrial substrate as compared with [12C]citrate, isocitrate or phosphoenolpyruvate. The concentration of L-malate required for half-maximal rate of efflux of citrate was 0.45 mM and the maximum velocity was 0.36 nmol min-1 mg-1 mitochondrial protein at 23 degrees C. This citrate transporter was inhibited by 1,2,3-benzenetricarboxylate and palmitoyl-CoA but not to the same extent as these compounds inhibit the tricarboxylate carrier in rat liver mitochondria. The apparent inability of these mitochondria to transport citrate in the inward direction necessitates the presence of a cytosolic citrate removal pathway. We propose that the enzymes of this pathway in rat heart could be ATP citrate (pro-3S)-lyase (EC 4.1.3.a) and carnitine acetyltransferase (EC 2.3.1.7), both of which we demonstrate to have adequate activity in both the fed and fasted state. An hypothesis has been put forward to account for the inhibition of rat heart phosphofructokinase by citrate in the fasted state incorporating these properties of the citrate transporter and ATP citrate (pro-3S)-lyase."} {"id": "PMID:1276982", "title": "In vitro biosynthesis of gamma-lipotropic hormone.", "content": "Sheep gamma-lipotropic hormone (gamma-LPH) is a pituitary polypeptide made of 58 amino acids and is formed of the first 58 residues of beta-lipotropic hormone (beta-LPH). The C-terminal portion (41-58) of gamma-LPH is identical with the structure of beta-melanophore-stimulating hormone (beta-MSH). We hypothetized in 1967 that beta-LPH could be the biological precursor of beta-MSH and that gamma-LPH could be an intermediate compound. We demonstrated in 1974 that beta-LPH is actively synthesized in the bovine pituitaries. We now studied the biosynthesis of gamma-LPH by monitoring the incorporation of radioactive amino acids in beef pituitary slices. We separated gamma-LPH from the other radioactive proteins with a method previously described. We characterized the radioactive proteins by ion-exchange chromatography, gel filtration and polyacrylamide gel electrophoresis. Our results show that radioactive gamma-LPH was actively synthesized. This gamma-LPH has all the chemical characteristics of nonradioactive gamma-LPH. However, in the conditions used, we were unable to demonstrate biosynthesis of beta-MSH. These results suggest that gamma-LPH is biosynthesized more slowly than beta-LPH and that the conversion into beta-MSH, if it exists, is a slow or subactive process in the species studied.", "contents": "In vitro biosynthesis of gamma-lipotropic hormone. Sheep gamma-lipotropic hormone (gamma-LPH) is a pituitary polypeptide made of 58 amino acids and is formed of the first 58 residues of beta-lipotropic hormone (beta-LPH). The C-terminal portion (41-58) of gamma-LPH is identical with the structure of beta-melanophore-stimulating hormone (beta-MSH). We hypothetized in 1967 that beta-LPH could be the biological precursor of beta-MSH and that gamma-LPH could be an intermediate compound. We demonstrated in 1974 that beta-LPH is actively synthesized in the bovine pituitaries. We now studied the biosynthesis of gamma-LPH by monitoring the incorporation of radioactive amino acids in beef pituitary slices. We separated gamma-LPH from the other radioactive proteins with a method previously described. We characterized the radioactive proteins by ion-exchange chromatography, gel filtration and polyacrylamide gel electrophoresis. Our results show that radioactive gamma-LPH was actively synthesized. This gamma-LPH has all the chemical characteristics of nonradioactive gamma-LPH. However, in the conditions used, we were unable to demonstrate biosynthesis of beta-MSH. These results suggest that gamma-LPH is biosynthesized more slowly than beta-LPH and that the conversion into beta-MSH, if it exists, is a slow or subactive process in the species studied."} {"id": "PMID:1276983", "title": "The absence of cell-specific histone in erythroid cell from rabbit marrow.", "content": "The histone complements of erythroid cells from anemic rabbit marrow and cell fractions enriched in orthochromatic erythroblasts were examined using a variety of techniques. None of these methods revealed the presence of a histone comparable to H5, the erythrocyte-specific histone of birds and fish. Purified histones H1, H2A, H2B, H3 and H4 from rabbit marrow nuclei showed no unusual amino acid compositions.", "contents": "The absence of cell-specific histone in erythroid cell from rabbit marrow. The histone complements of erythroid cells from anemic rabbit marrow and cell fractions enriched in orthochromatic erythroblasts were examined using a variety of techniques. None of these methods revealed the presence of a histone comparable to H5, the erythrocyte-specific histone of birds and fish. Purified histones H1, H2A, H2B, H3 and H4 from rabbit marrow nuclei showed no unusual amino acid compositions."} {"id": "PMID:1276984", "title": "Lipid composition of developing Xenopus laevis embryos.", "content": "The total lipid content, amount of phospholipid, proportions of major polar and neutral lipid classes, and the overall fatty acid composition were examined in Xenopus laevis embryos. No obvious differences were observed in any of the parameters between fertilization and hatching or between eggs produced by different females. The average lipid content per egg was 113 mug, 31.6 mug of which was phospholipid. The major phospholipids were phosphatidylcholine and sphingomyelin. The major fatty acids were palmitic and oleic acids, but polyunsaturated fatty acids were also present in substantial amounts. The results suggest that significant de novo synthesis of lipids does not occur until after hatching.", "contents": "Lipid composition of developing Xenopus laevis embryos. The total lipid content, amount of phospholipid, proportions of major polar and neutral lipid classes, and the overall fatty acid composition were examined in Xenopus laevis embryos. No obvious differences were observed in any of the parameters between fertilization and hatching or between eggs produced by different females. The average lipid content per egg was 113 mug, 31.6 mug of which was phospholipid. The major phospholipids were phosphatidylcholine and sphingomyelin. The major fatty acids were palmitic and oleic acids, but polyunsaturated fatty acids were also present in substantial amounts. The results suggest that significant de novo synthesis of lipids does not occur until after hatching."} {"id": "PMID:1276985", "title": "Observations on the effect of salicylate in fever and the regulation of body temperature against cold.", "content": "Prostaglandins appear to be mediators, within the hypothalamus, of heat production and conservation during fever. We have investigated a possible role of prostaglandins in the nonfebrile rabbit during thermoregulation in the cold. Shorn rabbits were placed in an environment of 20 degrees C, and rectal and ear skin temperatures, shivering and respiratory rates were measured. A continuous intravenous infusion of leucocyte pyrogen was given to establish a constant fever of approximately 1 degree C, and after observation of a stable febrile temperature for 90 min, a single injection of 300 mg of sodium salicylate, followed by a 1.5 mg/min infusion was then given. After the salicylate infusion was begun, rectal temperature began to fall, and reached nonfebrile levels within 90 min. Shivering activity ceased, respiratory rates increased, and in two animals, ear skin temperature increased. When these same rabbits were placed in an environment of 10 degrees C, at a time they were not febrile, and an identical amount of salicylate was given, rectal and ear skin temperatures, shivering and respiratory rates did not change. These results indicate that prostagladins do not appear to be involved in heat production and conservation in the nonfebrile rabbit.", "contents": "Observations on the effect of salicylate in fever and the regulation of body temperature against cold. Prostaglandins appear to be mediators, within the hypothalamus, of heat production and conservation during fever. We have investigated a possible role of prostaglandins in the nonfebrile rabbit during thermoregulation in the cold. Shorn rabbits were placed in an environment of 20 degrees C, and rectal and ear skin temperatures, shivering and respiratory rates were measured. A continuous intravenous infusion of leucocyte pyrogen was given to establish a constant fever of approximately 1 degree C, and after observation of a stable febrile temperature for 90 min, a single injection of 300 mg of sodium salicylate, followed by a 1.5 mg/min infusion was then given. After the salicylate infusion was begun, rectal temperature began to fall, and reached nonfebrile levels within 90 min. Shivering activity ceased, respiratory rates increased, and in two animals, ear skin temperature increased. When these same rabbits were placed in an environment of 10 degrees C, at a time they were not febrile, and an identical amount of salicylate was given, rectal and ear skin temperatures, shivering and respiratory rates did not change. These results indicate that prostagladins do not appear to be involved in heat production and conservation in the nonfebrile rabbit."} {"id": "PMID:1276986", "title": "Longitudinal extension of the pulmonary trunk during breathing in young rabbits: a possible factor in elastin fragmentation.", "content": "Corrosion casts of the pulmonary trunk and major branches of the pulmonary arteries of 39 rabbits were made from a silicone polymer. In half of the rabbits the casts were made with the lungs expanded and half with the lungs collapsed. The length of various segments of the casts were measured from magnified photographs. It was found that in rabbits less than 23 days old the pulmonary trunk is significantly longer when the lungs are expanded than when they are collapsed. This suggests that a repeated longitudinal extension of the vessel occurs during breathing. This effect disappears after 30 days of age, possibly because of elastin fragmentation. Between the ages of 23 and 30 days the growth in length and diameter of the pulmonary trunk undergoes a rapid acceleration. This may also be the result of elastin fragmentation. Whereas it may be that repeated longitudinal stress in the pulmonary trunk during breathing causes elastin in its media to fragment, one cannot exclude the possibility that other factors such as growth are responsible.", "contents": "Longitudinal extension of the pulmonary trunk during breathing in young rabbits: a possible factor in elastin fragmentation. Corrosion casts of the pulmonary trunk and major branches of the pulmonary arteries of 39 rabbits were made from a silicone polymer. In half of the rabbits the casts were made with the lungs expanded and half with the lungs collapsed. The length of various segments of the casts were measured from magnified photographs. It was found that in rabbits less than 23 days old the pulmonary trunk is significantly longer when the lungs are expanded than when they are collapsed. This suggests that a repeated longitudinal extension of the vessel occurs during breathing. This effect disappears after 30 days of age, possibly because of elastin fragmentation. Between the ages of 23 and 30 days the growth in length and diameter of the pulmonary trunk undergoes a rapid acceleration. This may also be the result of elastin fragmentation. Whereas it may be that repeated longitudinal stress in the pulmonary trunk during breathing causes elastin in its media to fragment, one cannot exclude the possibility that other factors such as growth are responsible."} {"id": "PMID:1276987", "title": "Dexclamol, a candidate for neuroleptanalgesia.", "content": "Dexclamol, a potent neuroleptic, was found to potentiate the anesthetic actions of halothane when given at relatively small dose to albino rats. This effect was further enhanced by the addition of phenoperidine, a potent analgesic, at doses that per se did not influence the effects of halothane. Droperidol was used as a standard. In potentiating the effects of halothane, dexclamol behaved both qualitatively and quantitatively in a manner similar to droperidol. Dexclamol, however, was approximately 37 times less potent than droperidol in antagonizing the vasopressor effects of epinephrine.", "contents": "Dexclamol, a candidate for neuroleptanalgesia. Dexclamol, a potent neuroleptic, was found to potentiate the anesthetic actions of halothane when given at relatively small dose to albino rats. This effect was further enhanced by the addition of phenoperidine, a potent analgesic, at doses that per se did not influence the effects of halothane. Droperidol was used as a standard. In potentiating the effects of halothane, dexclamol behaved both qualitatively and quantitatively in a manner similar to droperidol. Dexclamol, however, was approximately 37 times less potent than droperidol in antagonizing the vasopressor effects of epinephrine."} {"id": "PMID:1276988", "title": "Effective vascular compliance and venous diameter in dogs.", "content": "Total effective vascular compliance was measured repeatedly in open-chest dogs without circulatory arrest, utilizing a closed-circuit venous bypass system with a constant cardiac output. Mutual inductance coils were used to measure the diameter of the inferior vena cava above the diaphragm at the position where the pressure change was recorded during a volume load (lambde V). In all experiments, there was a relationship which tended to be curvilinear between the diameter of the inferior vena cava and the venous pressure before lambde V. No relationship was demonstrated between the initial diameter or pressure and the calculated effective vascular compliance. During aortic constriction or infusion of noradrenaline, the effective compliance was reduced in value at any given initial venous diameter and pressure. An unaltered venous diameter and plasma volume excluded the possibility of a large change in initial venous volume as a cause of the observed changes in compliance during aortic constriction or during infusion of noradrenaline. A relationship was observed between compliance and calculated venous wall tension so that as the wall tension, developed during a fixed volume load, increased, there was an associated reduction in compliance. These results demonstrate that the measurement of effective compliance provides an assessment of combined active and passive venous wall tension and venous tone.", "contents": "Effective vascular compliance and venous diameter in dogs. Total effective vascular compliance was measured repeatedly in open-chest dogs without circulatory arrest, utilizing a closed-circuit venous bypass system with a constant cardiac output. Mutual inductance coils were used to measure the diameter of the inferior vena cava above the diaphragm at the position where the pressure change was recorded during a volume load (lambde V). In all experiments, there was a relationship which tended to be curvilinear between the diameter of the inferior vena cava and the venous pressure before lambde V. No relationship was demonstrated between the initial diameter or pressure and the calculated effective vascular compliance. During aortic constriction or infusion of noradrenaline, the effective compliance was reduced in value at any given initial venous diameter and pressure. An unaltered venous diameter and plasma volume excluded the possibility of a large change in initial venous volume as a cause of the observed changes in compliance during aortic constriction or during infusion of noradrenaline. A relationship was observed between compliance and calculated venous wall tension so that as the wall tension, developed during a fixed volume load, increased, there was an associated reduction in compliance. These results demonstrate that the measurement of effective compliance provides an assessment of combined active and passive venous wall tension and venous tone."} {"id": "PMID:1276989", "title": "Unmasking of sympathetic vasoconstruction of the coronary vessels after acute administration of reserpine to dogs.", "content": "Acute intravenous administration of reserpine or pretreatment of dogs with Segontin selectively abolished coronary vasodilation and unmasked a constrictor response to stimulation of the cardiac sympathetics. In view of earlier findings of separate coronary vasomotor and cardiostimulatory sympathetic innervation, the results are interpreted to indicate the existence of reserpine-resistant short (vasomotor) and reserpine-sensitive long (cardiostimulatory) sympathetic postganglionic neurons.", "contents": "Unmasking of sympathetic vasoconstruction of the coronary vessels after acute administration of reserpine to dogs. Acute intravenous administration of reserpine or pretreatment of dogs with Segontin selectively abolished coronary vasodilation and unmasked a constrictor response to stimulation of the cardiac sympathetics. In view of earlier findings of separate coronary vasomotor and cardiostimulatory sympathetic innervation, the results are interpreted to indicate the existence of reserpine-resistant short (vasomotor) and reserpine-sensitive long (cardiostimulatory) sympathetic postganglionic neurons."} {"id": "PMID:1276990", "title": "Effect of 6-hydroxydopamine on diet-induced hyperlipidemia and atherosclerosis in the rat.", "content": "The effect of 6-hydroxydopamine (6-OH-dopamine) and of a cholesterol rich diet on the plasma and aortic cholesterol of female rats were studied. Both the diet and the 6-OH-dopamine produced an important increase in plasmatic and aortic cholesterol. A synergistic effect of these two treatments was observed on the plasma but not on the aortic cholesterol. The mechanism by which 6-OH-dopamine produces hypercholesterolemia and a increase in aortic cholesterol remains to be explained.", "contents": "Effect of 6-hydroxydopamine on diet-induced hyperlipidemia and atherosclerosis in the rat. The effect of 6-hydroxydopamine (6-OH-dopamine) and of a cholesterol rich diet on the plasma and aortic cholesterol of female rats were studied. Both the diet and the 6-OH-dopamine produced an important increase in plasmatic and aortic cholesterol. A synergistic effect of these two treatments was observed on the plasma but not on the aortic cholesterol. The mechanism by which 6-OH-dopamine produces hypercholesterolemia and a increase in aortic cholesterol remains to be explained."} {"id": "PMID:1276991", "title": "Species differences in the reactivation of organophosphate-inhibited plasma esterases by diacetylmonoxime.", "content": "A study was conducted to assess whether the protection afforded to organophosphatepoisoned animals by diacetylmonoxime (DAM) was correlated with the reactivation of non-essential aliesterases (AliE). In vitro, the DAM-catalyzed reactivation of plasma AliE and cholinesterases (psi ChE) of rat, rabbit and guinea pig inhibited by 10-5 M diisopropylphosphorofluoridate (DFP) and O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP) was investigated. Marked reactivation of the rat plasma enzymes was achieved with 10mM DAM. Higher concentrations (30 mM) were necessary for the slow reactivation of rabbit and guinea pig plasma AliE. Reactivation of the psiChE of these species was comparatively slow. Reactivation of DDVP-inhibited esterases proceeded in all species at a more rapid rate than those inhibited by DFP. The dependence of psiChE reactivation upon concomitant more rapid reactivation of AliE by DAM was demonstrated using Sephadex fractionated AliE and psiChE but only a marked effect was observed with the rat, suggesting that the plasma AliE of this species is functionally different. The in vitro observations were confirmed by in vivo studies in rats and rabbits. DAM (50 or 150 mg/kg), administered to atropinized rats 15 min before a lethal dose of DFP, protected the animals. Few severe toxic signs were observed and reactivation of both plasma AliE and psiChE occurred. In contrast, DAM protected the rabbit against a lethal dose of DFP but only reactivation of the erythrocyte acetylcholinesterase was observed.", "contents": "Species differences in the reactivation of organophosphate-inhibited plasma esterases by diacetylmonoxime. A study was conducted to assess whether the protection afforded to organophosphatepoisoned animals by diacetylmonoxime (DAM) was correlated with the reactivation of non-essential aliesterases (AliE). In vitro, the DAM-catalyzed reactivation of plasma AliE and cholinesterases (psi ChE) of rat, rabbit and guinea pig inhibited by 10-5 M diisopropylphosphorofluoridate (DFP) and O,O-dimethyl-2,2-dichlorovinyl phosphate (DDVP) was investigated. Marked reactivation of the rat plasma enzymes was achieved with 10mM DAM. Higher concentrations (30 mM) were necessary for the slow reactivation of rabbit and guinea pig plasma AliE. Reactivation of the psiChE of these species was comparatively slow. Reactivation of DDVP-inhibited esterases proceeded in all species at a more rapid rate than those inhibited by DFP. The dependence of psiChE reactivation upon concomitant more rapid reactivation of AliE by DAM was demonstrated using Sephadex fractionated AliE and psiChE but only a marked effect was observed with the rat, suggesting that the plasma AliE of this species is functionally different. The in vitro observations were confirmed by in vivo studies in rats and rabbits. DAM (50 or 150 mg/kg), administered to atropinized rats 15 min before a lethal dose of DFP, protected the animals. Few severe toxic signs were observed and reactivation of both plasma AliE and psiChE occurred. In contrast, DAM protected the rabbit against a lethal dose of DFP but only reactivation of the erythrocyte acetylcholinesterase was observed."} {"id": "PMID:1276992", "title": "Characteristics of accumulation of ephedrine in rabbit atria.", "content": "The characteristics of uptake of (not equal to)-(beta-14C)ephedrine were studied in isolated rabbit atria. Ephedrine was rapidly accumulated against the concentration gradient. From 5 X 10-7 to 10-2 M, uptake occurred at a uniform initial rate. Uptake was slightly inhibited by high concentrations of ouabain, cocaine, desipramine, lidocaine and phenethylamines, and by a reduction in the external Na+ concentration. Uptake was not, however, reduced by omission of K+ from the medium, by metabolic inhibitors or by a variety of drugs known to inhibit the extraneuronal uptake and binding of noradrenaline. Pretreatment of animals with 6-hydroxydopamine very significantly reduced the uptake of (not equal to)-(3H)metaraminol, but did not alter the uptake of ephedrine. It was concluded that the uptake of ephedrine in rabbit atria occurred predominantly in extraneuronal tissues possibly as a result of passive diffusion followed by binding.", "contents": "Characteristics of accumulation of ephedrine in rabbit atria. The characteristics of uptake of (not equal to)-(beta-14C)ephedrine were studied in isolated rabbit atria. Ephedrine was rapidly accumulated against the concentration gradient. From 5 X 10-7 to 10-2 M, uptake occurred at a uniform initial rate. Uptake was slightly inhibited by high concentrations of ouabain, cocaine, desipramine, lidocaine and phenethylamines, and by a reduction in the external Na+ concentration. Uptake was not, however, reduced by omission of K+ from the medium, by metabolic inhibitors or by a variety of drugs known to inhibit the extraneuronal uptake and binding of noradrenaline. Pretreatment of animals with 6-hydroxydopamine very significantly reduced the uptake of (not equal to)-(3H)metaraminol, but did not alter the uptake of ephedrine. It was concluded that the uptake of ephedrine in rabbit atria occurred predominantly in extraneuronal tissues possibly as a result of passive diffusion followed by binding."} {"id": "PMID:1276993", "title": "The growth of nitrogen-fixing Azotobacter chroococcum in continuous culture under intense aeration.", "content": "Azotobacter chroococcum (ATCC 7493) was grown in continuous culture with intense vortex aeration (stirring rate 1750 rpm) with up to 50% O2 in the gas phase. Under these conditions the dissolved O2 generally remained at zero while the cell growth rose to about twice the normally accepted value. The meaning of the term \"O2-limitation\" in N2-fixing A. chroococcum cultures is critically examined.", "contents": "The growth of nitrogen-fixing Azotobacter chroococcum in continuous culture under intense aeration. Azotobacter chroococcum (ATCC 7493) was grown in continuous culture with intense vortex aeration (stirring rate 1750 rpm) with up to 50% O2 in the gas phase. Under these conditions the dissolved O2 generally remained at zero while the cell growth rose to about twice the normally accepted value. The meaning of the term \"O2-limitation\" in N2-fixing A. chroococcum cultures is critically examined."} {"id": "PMID:1276994", "title": "[The Palmier date palm and Fusarium infection. II. Report on the stereochemistry of monosaccharides and their various derivatives and the growth of Fusarium oxysporum f.sp. albedinis (Killian et Maire) Gordon].", "content": "Fusarium oxysporum albedinis was grown in the presence of 20 different sugars or their derivatives. The results obtained were correlated with the stereochemical structure of the main oses. Osmotic phenomena as well as active and selective transport were used to explain differences in utilization of oses of very near structure. Based on the affinity of the fungus for mannose, a hypothesis is formulated concerning the fungus action in the host.", "contents": "[The Palmier date palm and Fusarium infection. II. Report on the stereochemistry of monosaccharides and their various derivatives and the growth of Fusarium oxysporum f.sp. albedinis (Killian et Maire) Gordon]. Fusarium oxysporum albedinis was grown in the presence of 20 different sugars or their derivatives. The results obtained were correlated with the stereochemical structure of the main oses. Osmotic phenomena as well as active and selective transport were used to explain differences in utilization of oses of very near structure. Based on the affinity of the fungus for mannose, a hypothesis is formulated concerning the fungus action in the host."} {"id": "PMID:1276995", "title": "Effect of chemicals used as nitrification inhibitors on the denitrification process.", "content": "Several chemicals used as nitrification inhibitors were tested to determine their effect on dentrification by a Pseudomonas sp. and in soil. Denitrification by the bacterium was suppressed by 2-chloro-6(-trichloromethyl)-pyridine (N-Serve) at a concentration of 50 ppm, while 2,5-dichloroaniline caused the accumulation of nitrite in the culture medium. The nitrification inhibitors had little effect on the denitrifying activity in soil under anaerobic conditions. 2-Sulfanilamidothiazole inhibited denitrification to some extent and samples supplied with potassium azide produced N2O rather than N2 as the predominant gas.", "contents": "Effect of chemicals used as nitrification inhibitors on the denitrification process. Several chemicals used as nitrification inhibitors were tested to determine their effect on dentrification by a Pseudomonas sp. and in soil. Denitrification by the bacterium was suppressed by 2-chloro-6(-trichloromethyl)-pyridine (N-Serve) at a concentration of 50 ppm, while 2,5-dichloroaniline caused the accumulation of nitrite in the culture medium. The nitrification inhibitors had little effect on the denitrifying activity in soil under anaerobic conditions. 2-Sulfanilamidothiazole inhibited denitrification to some extent and samples supplied with potassium azide produced N2O rather than N2 as the predominant gas."} {"id": "PMID:1276996", "title": "Urease-negative strains of Clostridium sordellii.", "content": "Twenty-seven of 37 non-toxigenic, urease-negative strains originally identified as Clostridium bifermentans that were isolated in the Antarctic are reidentified as C. sordellii by the tests for DNA-DNA homology, by the absence of mannose in the cell wall, and by growth inhibition of mannose. The test for cell wall sugar components of urease-negative and -positive strains of C. sordellii revealed that glucose, mannose, and rhamnose could not be detected in any of eight urease-negative strains used by galactose was detectable in seven of the eight strains and that glucose or galactose or both of the two sugars were present in the urease-positive strains tested.", "contents": "Urease-negative strains of Clostridium sordellii. Twenty-seven of 37 non-toxigenic, urease-negative strains originally identified as Clostridium bifermentans that were isolated in the Antarctic are reidentified as C. sordellii by the tests for DNA-DNA homology, by the absence of mannose in the cell wall, and by growth inhibition of mannose. The test for cell wall sugar components of urease-negative and -positive strains of C. sordellii revealed that glucose, mannose, and rhamnose could not be detected in any of eight urease-negative strains used by galactose was detectable in seven of the eight strains and that glucose or galactose or both of the two sugars were present in the urease-positive strains tested."} {"id": "PMID:1276997", "title": "Preparation and chemical properties of the outer membrane of a moderately halophilic gram-negative bacterium.", "content": "Outer membranes, almost free from peptidoglycan components, were prepared from a moderately halophilic gram-negative bacterium grown in a medium containing 2 M NaCl. The outer membrane was easily released, leaving mureinoplasts, by mild desalting in a 20% sucrose solution containing 50 mM tris(hydroxymethyl)aminomethane-HCl buffer, pH 7.8. The membrane was recovered by treatment with DNase I and CsCl buoyant density centrifugation. Chemical analyses revealed that the outer membrane was mainly composed of 31% protein, about 20% extractable lipids (mainly phospholipids), and lipopolysaccharides. The proteins had about 18 mol % excess of acidic over basic amino acids. The phospholipids comprised phosphatidyl ethanolamine, phosphatidyl glycerol, cardiolipin, and an unidentified phospholipid containing glucose, which seemed mainly associated with the outer membrane. The content of lipopolysaccharides in the outer membrane was calculated arbitrarily as 30% from the heptose content. A unique feature of these lipopolysaccharides seemed to be higher lipid content than found in lipopolysaccharides of other gram-negative bacteria. The major fatty acids of bound lipids of the outer membrane resembled those of the lipopolysaccharides obtained from cell envelope preparation and contained high concentrations of 3-hydroxy lauric acid.", "contents": "Preparation and chemical properties of the outer membrane of a moderately halophilic gram-negative bacterium. Outer membranes, almost free from peptidoglycan components, were prepared from a moderately halophilic gram-negative bacterium grown in a medium containing 2 M NaCl. The outer membrane was easily released, leaving mureinoplasts, by mild desalting in a 20% sucrose solution containing 50 mM tris(hydroxymethyl)aminomethane-HCl buffer, pH 7.8. The membrane was recovered by treatment with DNase I and CsCl buoyant density centrifugation. Chemical analyses revealed that the outer membrane was mainly composed of 31% protein, about 20% extractable lipids (mainly phospholipids), and lipopolysaccharides. The proteins had about 18 mol % excess of acidic over basic amino acids. The phospholipids comprised phosphatidyl ethanolamine, phosphatidyl glycerol, cardiolipin, and an unidentified phospholipid containing glucose, which seemed mainly associated with the outer membrane. The content of lipopolysaccharides in the outer membrane was calculated arbitrarily as 30% from the heptose content. A unique feature of these lipopolysaccharides seemed to be higher lipid content than found in lipopolysaccharides of other gram-negative bacteria. The major fatty acids of bound lipids of the outer membrane resembled those of the lipopolysaccharides obtained from cell envelope preparation and contained high concentrations of 3-hydroxy lauric acid."} {"id": "PMID:1276998", "title": "Two toxic indole alkaloids from Penicillium islandicum.", "content": "Two new isomeric metabolites, toxins A and B, were isolated from culture extracts of Penicillium islandicum. Both toxins had a molecular formula of C16H15O2N2Cl, and physical and chemical analyses indicated that they were indole alkaloids. LD50 of toxin A was about 75-125 mg/kg in day-old cockerels. Insufficient toxin B was available to determine accurate LD50 values. Toxin A moderately inhibited growth of wheat coleoptiles but did not inhibit growth of week-old intact corn and bean plants. Toxin B showed no plant-growth inhibition.", "contents": "Two toxic indole alkaloids from Penicillium islandicum. Two new isomeric metabolites, toxins A and B, were isolated from culture extracts of Penicillium islandicum. Both toxins had a molecular formula of C16H15O2N2Cl, and physical and chemical analyses indicated that they were indole alkaloids. LD50 of toxin A was about 75-125 mg/kg in day-old cockerels. Insufficient toxin B was available to determine accurate LD50 values. Toxin A moderately inhibited growth of wheat coleoptiles but did not inhibit growth of week-old intact corn and bean plants. Toxin B showed no plant-growth inhibition."} {"id": "PMID:1276999", "title": "Nematophagous fungi: three new species of Myzocytium.", "content": "Three species of Myzocytium parasitic on nematodes are described as new. In M. papillatum the zoospores encyst directly on the host cuticle before penetration. This species produces smooth, spherical oospores. In M. glutinosporum the biflagellate zoospores do not attack the host directly; after encystment they produce a spherical adhesive bud which allows the spores to adhere to the cuticle of passing nematodes. This species produces echinulate, spherical oospores. In M. anomalum the primary spores are aplanospores. After a dormant phase, and when suitably stimulated, these aplanospores change into biflagellate zoospores and the latter encyst on the host cuticle. No sexual state is known in this species. Persistence is by means of thick-walled, spherical chlamydospores.", "contents": "Nematophagous fungi: three new species of Myzocytium. Three species of Myzocytium parasitic on nematodes are described as new. In M. papillatum the zoospores encyst directly on the host cuticle before penetration. This species produces smooth, spherical oospores. In M. glutinosporum the biflagellate zoospores do not attack the host directly; after encystment they produce a spherical adhesive bud which allows the spores to adhere to the cuticle of passing nematodes. This species produces echinulate, spherical oospores. In M. anomalum the primary spores are aplanospores. After a dormant phase, and when suitably stimulated, these aplanospores change into biflagellate zoospores and the latter encyst on the host cuticle. No sexual state is known in this species. Persistence is by means of thick-walled, spherical chlamydospores."} {"id": "PMID:1277000", "title": "Release of bacterial alkaline phosphatase in the rumen of cattle fed a feedlot bloat-provoking diet or a hay diet.", "content": "Alkaline phosphatase (APase) was present in the bovine rumen in both cell-free and cell-associated states and levels of the enzyme varied with dietary regime. Reaction product deposition showed that the enzyme was associated with the mixed bacterial population. No enzyme was observed to be associated with protozoa. Trace activity of APase was also detected in the saliva. The presence of large amounts of APase in cell-free rumen fluid of cattle fed fine concentrate feed is believed to be due, in part, to the breakage of bacterial cells that occurs in the rumen.", "contents": "Release of bacterial alkaline phosphatase in the rumen of cattle fed a feedlot bloat-provoking diet or a hay diet. Alkaline phosphatase (APase) was present in the bovine rumen in both cell-free and cell-associated states and levels of the enzyme varied with dietary regime. Reaction product deposition showed that the enzyme was associated with the mixed bacterial population. No enzyme was observed to be associated with protozoa. Trace activity of APase was also detected in the saliva. The presence of large amounts of APase in cell-free rumen fluid of cattle fed fine concentrate feed is believed to be due, in part, to the breakage of bacterial cells that occurs in the rumen."} {"id": "PMID:1277002", "title": "Comparative zone electrophoresis of esterases of Staphylococcus species isolated from mammalian skin.", "content": "The electrophoretic mobilities of non-specific esterases in vertical polyacrylamide slab gels were determined for 184 strains of staphylococci, representing a total of 18 proposed species and subspecies. Markedly uniform esterase patterns were seen within species demonstrating a high degree of human host specificity, while those species demonstrating a wide host range were polytypic and often showed considerable polymorphism. The unique banding patterns found in several species indicate that this technique may serve as a valuable aid to existing taxonomic schemes. Starch gel electrophoresis of representative strains usually produced sharper esterase bands than were found with polyacrylamide electrophoresis. However, the additional molecular-sieving effect produced by the polyacrylamide gels differentiated esterases to a greater extent.", "contents": "Comparative zone electrophoresis of esterases of Staphylococcus species isolated from mammalian skin. The electrophoretic mobilities of non-specific esterases in vertical polyacrylamide slab gels were determined for 184 strains of staphylococci, representing a total of 18 proposed species and subspecies. Markedly uniform esterase patterns were seen within species demonstrating a high degree of human host specificity, while those species demonstrating a wide host range were polytypic and often showed considerable polymorphism. The unique banding patterns found in several species indicate that this technique may serve as a valuable aid to existing taxonomic schemes. Starch gel electrophoresis of representative strains usually produced sharper esterase bands than were found with polyacrylamide electrophoresis. However, the additional molecular-sieving effect produced by the polyacrylamide gels differentiated esterases to a greater extent."} {"id": "PMID:1277003", "title": "Some properties of an unidentified halophile: growth characteristics, internal salt concentration, and morphology.", "content": "An unidentified halophile isolated from plates of a complex agar medium containing 4.25 M NaCl showed optimum growth in broths containing 0.5-1.0 M NaCl but exhibited a wide range of growth from 0.045-4.5 M. The organism can be classified as a facultative halophile with wide salt tolerance. Logarithmic phase cells grown in media containing 0.5 M NaCl were rod-shaped in long chains which changed to smaller, single, or paired cells in stationary growth. The internal Na+ and K+ concentrations were 0.05 M and 0.34 M for logarithmic phase cells and 0.29 and 0.32 M for stationary phase cells. In 4.3 M NaCl media the cells were rod-shaped throughout the growth cycle, occurring primarily in pairs. The internal Na+ K\" concentrations in cells in logarithmic phase growth were 0.62 M and 0.58 M while in stationary phase growth these values were 1.01 M and 0.66 M respectively. In contrast, logarithmic phase cells of the extreme halophile Halobacterium cutirubrum had internal Na+ and K+ concentrations of 0.80 M and 5.32 M when grown in 3.3 M NaCl. The internal Na+ and K+ concentrations, therefore, in the unidentified halophile do not resemble those found in H. cutirubrum but are much closer to those present in Escherichia coli.", "contents": "Some properties of an unidentified halophile: growth characteristics, internal salt concentration, and morphology. An unidentified halophile isolated from plates of a complex agar medium containing 4.25 M NaCl showed optimum growth in broths containing 0.5-1.0 M NaCl but exhibited a wide range of growth from 0.045-4.5 M. The organism can be classified as a facultative halophile with wide salt tolerance. Logarithmic phase cells grown in media containing 0.5 M NaCl were rod-shaped in long chains which changed to smaller, single, or paired cells in stationary growth. The internal Na+ and K+ concentrations were 0.05 M and 0.34 M for logarithmic phase cells and 0.29 and 0.32 M for stationary phase cells. In 4.3 M NaCl media the cells were rod-shaped throughout the growth cycle, occurring primarily in pairs. The internal Na+ K\" concentrations in cells in logarithmic phase growth were 0.62 M and 0.58 M while in stationary phase growth these values were 1.01 M and 0.66 M respectively. In contrast, logarithmic phase cells of the extreme halophile Halobacterium cutirubrum had internal Na+ and K+ concentrations of 0.80 M and 5.32 M when grown in 3.3 M NaCl. The internal Na+ and K+ concentrations, therefore, in the unidentified halophile do not resemble those found in H. cutirubrum but are much closer to those present in Escherichia coli."} {"id": "PMID:1277004", "title": "The effect of ribonuclease on the penetration of R17 phage A-protein and RNA.", "content": "In an attempt to throw further light on the relationship of R17 phage RNA and A-protein during the early stages of infection, studies were carried out to determine the effect of ribonuclease (ribonuclease I, EC 3.1.4.22) on the ability of these two phage components to penetrate into host bacteria. It was found that the penetration of phage RNA is affected by ribonuclease concentrations as low as 0.1 mug/ml, while the penetration of phage A-protein was unaffected by ribonuclease concentrations as high as 20 mug/ml. In addition, it was found that a significant fraction of the phage RNA is resistant to the ribonuclease effect. This RNase-resistant portion of the phage population increased with increasing phage concentrations, and gave rise to the penetration of intact, 28S RNA molecules that produced the expected number of infectious centers. These findings are discussed in terms of a model for phage RNA injection in which the A-protein functions both as an attachment organelle and a pilot protein that guides the RNA from the capsid to the exterior surface of the F pilus, and thence into the host bacterium.", "contents": "The effect of ribonuclease on the penetration of R17 phage A-protein and RNA. In an attempt to throw further light on the relationship of R17 phage RNA and A-protein during the early stages of infection, studies were carried out to determine the effect of ribonuclease (ribonuclease I, EC 3.1.4.22) on the ability of these two phage components to penetrate into host bacteria. It was found that the penetration of phage RNA is affected by ribonuclease concentrations as low as 0.1 mug/ml, while the penetration of phage A-protein was unaffected by ribonuclease concentrations as high as 20 mug/ml. In addition, it was found that a significant fraction of the phage RNA is resistant to the ribonuclease effect. This RNase-resistant portion of the phage population increased with increasing phage concentrations, and gave rise to the penetration of intact, 28S RNA molecules that produced the expected number of infectious centers. These findings are discussed in terms of a model for phage RNA injection in which the A-protein functions both as an attachment organelle and a pilot protein that guides the RNA from the capsid to the exterior surface of the F pilus, and thence into the host bacterium."} {"id": "PMID:1277005", "title": "Effects of temperature on the growth of psychrophilic bacteria from glaciers.", "content": "Growth of five strains of psychrophilic bacteria (four Arthrobacter and one Pseudomonas) isolated from glacial deposits was studied at different temperatures. Three strains were facultative psychrophiles, having an optimum temperature for growth at about 25-28 degrees C and a maximum at about 32-34 degrees C. The two Arthrobacter glacialis strains were found to be obligate psychrophiles with an optimum at 13-15 degrees C and a maximum at 18 degrees C. Arrhenius plots showed that A. glacialis could compete with the facultative psychrophilic bacteria only at 0 degrees C, that is, the temperature of its natural environment. The psychrophilic Arthrobacter species studied here are more resistant to thermal stress than are marine psychrophilic bacteria. For Arthrobacter, in contrast to Pseudomonas, temperatures above the optimum induced formation of filaments and abnormal cells. The culture turbidity increased 10 to 30 times, whereas viable count tended to decrease. The thermal block seems to prevent cell wall synthesis and septation, but at a different step for each species.", "contents": "Effects of temperature on the growth of psychrophilic bacteria from glaciers. Growth of five strains of psychrophilic bacteria (four Arthrobacter and one Pseudomonas) isolated from glacial deposits was studied at different temperatures. Three strains were facultative psychrophiles, having an optimum temperature for growth at about 25-28 degrees C and a maximum at about 32-34 degrees C. The two Arthrobacter glacialis strains were found to be obligate psychrophiles with an optimum at 13-15 degrees C and a maximum at 18 degrees C. Arrhenius plots showed that A. glacialis could compete with the facultative psychrophilic bacteria only at 0 degrees C, that is, the temperature of its natural environment. The psychrophilic Arthrobacter species studied here are more resistant to thermal stress than are marine psychrophilic bacteria. For Arthrobacter, in contrast to Pseudomonas, temperatures above the optimum induced formation of filaments and abnormal cells. The culture turbidity increased 10 to 30 times, whereas viable count tended to decrease. The thermal block seems to prevent cell wall synthesis and septation, but at a different step for each species."} {"id": "PMID:1277006", "title": "The fine structure of conidial development in the genus Torula. III. T. graminis Desm.", "content": "Torula graminis produced blastoconidia in acropetalous chains after the evagination of a characteristic conidiogenous cell. Conidia consisted of up to 15 cells and their cell wall was differentiated into an outer melanized zone and an inner hyaline zone. A consistent cytoplasmic feature of conidial cells was the presence of dictyosomal-like membranous stacks often closely associated with the nucleus. Vesicles that developed from the dictyosomal-like cisternae were probably involved in conidial wall synthesis.", "contents": "The fine structure of conidial development in the genus Torula. III. T. graminis Desm. Torula graminis produced blastoconidia in acropetalous chains after the evagination of a characteristic conidiogenous cell. Conidia consisted of up to 15 cells and their cell wall was differentiated into an outer melanized zone and an inner hyaline zone. A consistent cytoplasmic feature of conidial cells was the presence of dictyosomal-like membranous stacks often closely associated with the nucleus. Vesicles that developed from the dictyosomal-like cisternae were probably involved in conidial wall synthesis."} {"id": "PMID:1277007", "title": "Repression of the acid phosphatase of Saccharomyces bisporus in relation to the polyphosphate content of the cells.", "content": "The relationship between the level of stored polyphosphate in growing cells of Saccharomyces bisporus and the repressing or derepression of the synthesis of the enzyme acid phosphatase (EC 3.1.3.2) was investigated. Time-course studies showed that there is no correlation between the cellular concentrations of either polyphosphate or orthophosphate and the ability of the cells to form this enzyme. The only compound investigated that was capable of repressing acid phosphatase synthesis was orthophosphate in the growth medium (i.e. orthophosphate outside the cell).", "contents": "Repression of the acid phosphatase of Saccharomyces bisporus in relation to the polyphosphate content of the cells. The relationship between the level of stored polyphosphate in growing cells of Saccharomyces bisporus and the repressing or derepression of the synthesis of the enzyme acid phosphatase (EC 3.1.3.2) was investigated. Time-course studies showed that there is no correlation between the cellular concentrations of either polyphosphate or orthophosphate and the ability of the cells to form this enzyme. The only compound investigated that was capable of repressing acid phosphatase synthesis was orthophosphate in the growth medium (i.e. orthophosphate outside the cell)."} {"id": "PMID:1277008", "title": "[Antibacterial effect of various mycotoxins and fungal metabolites against Bacillus thuringiensis (Berliner) strains sensitive or resistant to aflatoxin B1].", "content": "Antimicrobial activity of pure preparations of mycotoxins and fungal metabolites was studied against strains of Bacillus thuringiensis (Berliner). Two resistant strains, called stable-variant, were isolated after treatment with high concentrations of aflatoxin B1. These strains were then resistant also towards compounds with a double furan system (aflatoxins B1, B2, G1, G2, and sterigmatocystin).", "contents": "[Antibacterial effect of various mycotoxins and fungal metabolites against Bacillus thuringiensis (Berliner) strains sensitive or resistant to aflatoxin B1]. Antimicrobial activity of pure preparations of mycotoxins and fungal metabolites was studied against strains of Bacillus thuringiensis (Berliner). Two resistant strains, called stable-variant, were isolated after treatment with high concentrations of aflatoxin B1. These strains were then resistant also towards compounds with a double furan system (aflatoxins B1, B2, G1, G2, and sterigmatocystin)."} {"id": "PMID:1277009", "title": "Long-chain n-alkanes occurring during microbial degradation of petroleum.", "content": "Five axenic cultures and a mixed culture were examined for ability to degrade South Louisiana, Brass River Nigerian, Anaco Venezuelan, and Altamont crude oils. A wax was observed during microbial degradation of Altamont crude oil, but not during weathering of the oil. The high-boiling n-alkanes in the wax were associated with microbial degradation of the oil and appeared to be similar to components of tarballs found in the open ocean.", "contents": "Long-chain n-alkanes occurring during microbial degradation of petroleum. Five axenic cultures and a mixed culture were examined for ability to degrade South Louisiana, Brass River Nigerian, Anaco Venezuelan, and Altamont crude oils. A wax was observed during microbial degradation of Altamont crude oil, but not during weathering of the oil. The high-boiling n-alkanes in the wax were associated with microbial degradation of the oil and appeared to be similar to components of tarballs found in the open ocean."} {"id": "PMID:1277010", "title": "Electron microscopy of antibody-labelled cells of Streptococcus mutans.", "content": "Examination of immune complexes between cells of Streptococcus mutans and homologous antiserum by the techniques of thin-sectioning and freeze-etching revealed that the cells were embedded within and extensive matrix 80-90 nm thick with defined boundaries.", "contents": "Electron microscopy of antibody-labelled cells of Streptococcus mutans. Examination of immune complexes between cells of Streptococcus mutans and homologous antiserum by the techniques of thin-sectioning and freeze-etching revealed that the cells were embedded within and extensive matrix 80-90 nm thick with defined boundaries."} {"id": "PMID:1277014", "title": "Distension arthrography of the shoulder joint.", "content": "Pain and stiffness resulting from degenerative disease of the rotator cuff of the glenohumeral joint is not always self-limiting. In a few patients, the symptoms persist despite medication and physiotherapy. Distension arthrography, a method of hydrostatic manipulation, has been used in six such patients; five recovered full range of abduction and rotation and the sixth was improved. It is concluded that distension arthrography should be part of the treatment of intractable pain stiffness of the shoulder joint.", "contents": "Distension arthrography of the shoulder joint. Pain and stiffness resulting from degenerative disease of the rotator cuff of the glenohumeral joint is not always self-limiting. In a few patients, the symptoms persist despite medication and physiotherapy. Distension arthrography, a method of hydrostatic manipulation, has been used in six such patients; five recovered full range of abduction and rotation and the sixth was improved. It is concluded that distension arthrography should be part of the treatment of intractable pain stiffness of the shoulder joint."} {"id": "PMID:1277015", "title": "Knee arthrodesis: long-term results.", "content": "A review of 41 patients in whom knee fusion was performed mainly for degenerative arthritis and sepsis disclosed that only 15% of patients were without complications. Complications were numerous and appeared both early and late - persistent knee and back pain were the most common. Many patients were unable to return to work or to participate in social activities. The optimal position for fusion is 15 to 20 degrees of flexion, which results in a smoother gait and less difficulty for the patient in driving a car. Because of the continued refinement in total knee joint replacement, the indications for knee arthrodesis should be confined to the treatment of chronic infection and failed total joint replacement.", "contents": "Knee arthrodesis: long-term results. A review of 41 patients in whom knee fusion was performed mainly for degenerative arthritis and sepsis disclosed that only 15% of patients were without complications. Complications were numerous and appeared both early and late - persistent knee and back pain were the most common. Many patients were unable to return to work or to participate in social activities. The optimal position for fusion is 15 to 20 degrees of flexion, which results in a smoother gait and less difficulty for the patient in driving a car. Because of the continued refinement in total knee joint replacement, the indications for knee arthrodesis should be confined to the treatment of chronic infection and failed total joint replacement."} {"id": "PMID:1277016", "title": "Value of intraoperative arteriography in arterial embolectomy surgery.", "content": "Clinical assessment of the adequacy of arterial embolectomy and reconstruction is often unsatisfactory and inadequate. Objective information on the state of the distal circulation can be readily obtained at the time of surgery by arteriography. Illustrative cases demonstrating the usefulness of control arteriography obtained during the surgical procedure are presented.", "contents": "Value of intraoperative arteriography in arterial embolectomy surgery. Clinical assessment of the adequacy of arterial embolectomy and reconstruction is often unsatisfactory and inadequate. Objective information on the state of the distal circulation can be readily obtained at the time of surgery by arteriography. Illustrative cases demonstrating the usefulness of control arteriography obtained during the surgical procedure are presented."} {"id": "PMID:1277018", "title": "Fatal cerebral embolus - a complication of left ventricular venting.", "content": "A 3-year-old child died following a routine tetralogy of Fallot repair. Death was caused by a cerebral embolus. Injury to the left ventricle during left ventricular venting resulted in an apical myocardial infarct. The embolic source was a mural thrombus covering the area of infarction. A technique is described whereby left ventricular venting can be avoided during open-heart surgery in small patients.", "contents": "Fatal cerebral embolus - a complication of left ventricular venting. A 3-year-old child died following a routine tetralogy of Fallot repair. Death was caused by a cerebral embolus. Injury to the left ventricle during left ventricular venting resulted in an apical myocardial infarct. The embolic source was a mural thrombus covering the area of infarction. A technique is described whereby left ventricular venting can be avoided during open-heart surgery in small patients."} {"id": "PMID:1277019", "title": "Surgical rates in the Canadian provinces, 1968 to 1972.", "content": "Canadian and provincial rates for eight elective and seven nonelective operations were determined from 1968 through 1972. Of the elective procedures considered, the Canadian tonsillectomy rate decreased substantially and rates for hysterectomy and cholecystectomy showed large increases. The provinces reflected national trends for these three operations. Except for coletomy, which increased 36%, rates for the nonelective procedures showed little change. Correlations between the numbers of surgical personnel and the elective surgery rates in the provinces were demonstrated in 3 of the 5 years; these are best shown at the extremes. Newfoundland had the fewest surgeons, a bed: population ratio below the national average and the lowest combined elective surgical rate; Alberta ranked high in all three categories. In the seven other provinces, there was less variation in the number of surgeons, hospital beds and elective surgical rates. Provinces with extensive insurance coverage prior to universal medical insurance reduced their combined elective surgery rate, while provinces where fewer people were insured showed increases. In the absence of different methods of payment for surgical services and marginal changes in the number of hospital beds and the number of surgeons, more insured persons produced more elective surgery.", "contents": "Surgical rates in the Canadian provinces, 1968 to 1972. Canadian and provincial rates for eight elective and seven nonelective operations were determined from 1968 through 1972. Of the elective procedures considered, the Canadian tonsillectomy rate decreased substantially and rates for hysterectomy and cholecystectomy showed large increases. The provinces reflected national trends for these three operations. Except for coletomy, which increased 36%, rates for the nonelective procedures showed little change. Correlations between the numbers of surgical personnel and the elective surgery rates in the provinces were demonstrated in 3 of the 5 years; these are best shown at the extremes. Newfoundland had the fewest surgeons, a bed: population ratio below the national average and the lowest combined elective surgical rate; Alberta ranked high in all three categories. In the seven other provinces, there was less variation in the number of surgeons, hospital beds and elective surgical rates. Provinces with extensive insurance coverage prior to universal medical insurance reduced their combined elective surgery rate, while provinces where fewer people were insured showed increases. In the absence of different methods of payment for surgical services and marginal changes in the number of hospital beds and the number of surgeons, more insured persons produced more elective surgery."} {"id": "PMID:1277020", "title": "Technique for cardiopulmonary bypass in the goat.", "content": "The goat is an ideal animal for intracardiac surgical investigation. The animal is docile and easy to care for; it has an ideal heart size, a high cardiac output and a long life expectancy. The animal tolerates cardiopulmonary bypass well and does not require blood transfusion. Anoxic cardiac arrest is tolerated for up to 35 minutes. Initial experience in 36 animals with operations on the right side of the heart resulted in a 72% long-term survival.", "contents": "Technique for cardiopulmonary bypass in the goat. The goat is an ideal animal for intracardiac surgical investigation. The animal is docile and easy to care for; it has an ideal heart size, a high cardiac output and a long life expectancy. The animal tolerates cardiopulmonary bypass well and does not require blood transfusion. Anoxic cardiac arrest is tolerated for up to 35 minutes. Initial experience in 36 animals with operations on the right side of the heart resulted in a 72% long-term survival."} {"id": "PMID:1277021", "title": "Sudden hemolysis indicating prosthetic valve dysfunction.", "content": "Ten months after aortic valve replacement (Bj\u00f6rk-Shiley prosthesis) a 57-year-old man had thrombotic encapsulation of his prosthetic valve. The only clinical manifestation of this serious complication was gross hemoglobinuria. The management of the patient is described. The slightest change in the condition of a patient after prosthetic valve replacement should be viewed as a possible sign of thrombosis.", "contents": "Sudden hemolysis indicating prosthetic valve dysfunction. Ten months after aortic valve replacement (Bj\u00f6rk-Shiley prosthesis) a 57-year-old man had thrombotic encapsulation of his prosthetic valve. The only clinical manifestation of this serious complication was gross hemoglobinuria. The management of the patient is described. The slightest change in the condition of a patient after prosthetic valve replacement should be viewed as a possible sign of thrombosis."} {"id": "PMID:1277044", "title": "Gallium-67-citrate scintiscanning in the search for occult primary malignant tumours.", "content": "Fifty consecutive patients in whom occult primary malignant disease was suspected underwent scintiscanning of the head, neck and trunk with gallium-67-citrate. In 17 patients a carcinoma was correctly identified as to presence and approximate location. In another seven patients the site of the primary tumour was identified from the scan and confirmed by radiologic study but no histopathological diagnosis, except for metastatic anaplastic carcinoma, was made. In another five patients the many abnormalities on the scan did not permit identification of a possible site of the primary tumour. Eleven patients had normal scintiscans and no evidence of malignant disease on follow-up. In seven patients with proven carcinoma false-negative results were obtained: no uptake of the radioisotope was detected, even at the sites of known disease. In three patients false-positive uptake of the radiotracer was observed; two had benign disease and one had a malignant tumour remote from the scan abnormality.", "contents": "Gallium-67-citrate scintiscanning in the search for occult primary malignant tumours. Fifty consecutive patients in whom occult primary malignant disease was suspected underwent scintiscanning of the head, neck and trunk with gallium-67-citrate. In 17 patients a carcinoma was correctly identified as to presence and approximate location. In another seven patients the site of the primary tumour was identified from the scan and confirmed by radiologic study but no histopathological diagnosis, except for metastatic anaplastic carcinoma, was made. In another five patients the many abnormalities on the scan did not permit identification of a possible site of the primary tumour. Eleven patients had normal scintiscans and no evidence of malignant disease on follow-up. In seven patients with proven carcinoma false-negative results were obtained: no uptake of the radioisotope was detected, even at the sites of known disease. In three patients false-positive uptake of the radiotracer was observed; two had benign disease and one had a malignant tumour remote from the scan abnormality."} {"id": "PMID:1277057", "title": "Evaluation of the normal range of values for uptake of radioactive iodine by the thyroid gland.", "content": "Uptake of radioactive iodine by the thyroid gland after oral administration of 75 muCi was determined in 1971-72 in 60 euthyroid female volunteers from the North Shore of Vancouver. Values were as low as 3% at 4 hours and 7% at 24 hours in subjects otherwise proven to be euthyroid. The highest values found were 13 and 26% at 4 and 24 hours. The effective thyroxine ratios were all within the accepted normal range. However, more than half of the volunteers showed some enlargement of the thyroid gland. These results suggest an increased iodine pool in the subjects, the likley source being iodine in mild, dairy products and erythrosine, a colouring agent in foods and pharmaceutical products. Potassium iodate, used sometimes in bread baking, contributed little to this pool in our sample. Subjects were, on the average, 9 to 25% heavier than their peers 20 years ago.", "contents": "Evaluation of the normal range of values for uptake of radioactive iodine by the thyroid gland. Uptake of radioactive iodine by the thyroid gland after oral administration of 75 muCi was determined in 1971-72 in 60 euthyroid female volunteers from the North Shore of Vancouver. Values were as low as 3% at 4 hours and 7% at 24 hours in subjects otherwise proven to be euthyroid. The highest values found were 13 and 26% at 4 and 24 hours. The effective thyroxine ratios were all within the accepted normal range. However, more than half of the volunteers showed some enlargement of the thyroid gland. These results suggest an increased iodine pool in the subjects, the likley source being iodine in mild, dairy products and erythrosine, a colouring agent in foods and pharmaceutical products. Potassium iodate, used sometimes in bread baking, contributed little to this pool in our sample. Subjects were, on the average, 9 to 25% heavier than their peers 20 years ago."} {"id": "PMID:1277058", "title": "Application of special diagnostic techniques in the management of nodular goitre.", "content": "The primary challenge in the management of nodular goitre is to establish which thyroid nodules are malignant. Since selection of patients for operation on the basis of palpation of nodules alone gives a low yield of malignant disease, physicians have sought criteria for selection that combine the information obtained from special laboratory procedures with thoughtful clinical appraisal. Such special procedures, which include radioisotope scintiscanning, echography by B-mode ultrasonography, and either large- or fine-needle aspiration and cytologic examination of the aspirate, are considered valuable in a proposed clinical approach to the management of thyroid nodules.", "contents": "Application of special diagnostic techniques in the management of nodular goitre. The primary challenge in the management of nodular goitre is to establish which thyroid nodules are malignant. Since selection of patients for operation on the basis of palpation of nodules alone gives a low yield of malignant disease, physicians have sought criteria for selection that combine the information obtained from special laboratory procedures with thoughtful clinical appraisal. Such special procedures, which include radioisotope scintiscanning, echography by B-mode ultrasonography, and either large- or fine-needle aspiration and cytologic examination of the aspirate, are considered valuable in a proposed clinical approach to the management of thyroid nodules."} {"id": "PMID:1277059", "title": "A functioning pleomorphic carcinoma of the thyroid.", "content": "A metastasizing functioning pleomorphic carcinoma of the thyroid displayed a morphologic piture ranging from follicular to sarcomatous and carcinoid-like patterns. Spindle-cell elements were believed to be the result of metaplasia of the follicular epithelium. Development of carcinoid-like lesions in the secondary deposits of tumour supported the contention that so-called parafollicular or c-cells may be a phenomenon of metaplasia and not a histologic entity. The tumour was associated with a chromophobe adenoma of the pituitary and a benign schwannoma of the stomach. Clinically the patient did not show any other endocrinologic abnormalities and lived for 4 years from the time of diagnosis of the thyroid tumour.", "contents": "A functioning pleomorphic carcinoma of the thyroid. A metastasizing functioning pleomorphic carcinoma of the thyroid displayed a morphologic piture ranging from follicular to sarcomatous and carcinoid-like patterns. Spindle-cell elements were believed to be the result of metaplasia of the follicular epithelium. Development of carcinoid-like lesions in the secondary deposits of tumour supported the contention that so-called parafollicular or c-cells may be a phenomenon of metaplasia and not a histologic entity. The tumour was associated with a chromophobe adenoma of the pituitary and a benign schwannoma of the stomach. Clinically the patient did not show any other endocrinologic abnormalities and lived for 4 years from the time of diagnosis of the thyroid tumour."} {"id": "PMID:1277060", "title": "False left ventricular aneurysm as a complication of open heart surgery.", "content": "A false aneurysm developed at the site of left ventricular venting in an 8-year-old boy who had undergone aortic valve commissurotomy under cardiopulmonary bypass. The diagnosis was made by clinical examination and chest radiography and confirmed by left ventricular cineangiography. The aneurysm was successfully resected.", "contents": "False left ventricular aneurysm as a complication of open heart surgery. A false aneurysm developed at the site of left ventricular venting in an 8-year-old boy who had undergone aortic valve commissurotomy under cardiopulmonary bypass. The diagnosis was made by clinical examination and chest radiography and confirmed by left ventricular cineangiography. The aneurysm was successfully resected."} {"id": "PMID:1277061", "title": "Yellow-nail syndrome: report of three cases.", "content": "The yellow nail syndrome, a combination of yellow discolouration of and dystrophic changes in the nails, pleural effusions and lymphedema, is thought to be relatively rare; to date 44 cases have been reported. Of a further three patients with this syndrome, one had all three features, one had the yellow nails alone and the other had pleural effusions and lymphedema without classic nail changes. Each had recurrent lower respiratory tract infections; and of all 47, chronic pulmonary infections occurred in approximately one quarter and were frequently associated with chronic sinus infections. The underlying abnormality is presumed to be a congenital defect of the lymphatics, but so far this has not been demonstrated to be the cause of the nail changes, the pathogenesis of which remains obscure.", "contents": "Yellow-nail syndrome: report of three cases. The yellow nail syndrome, a combination of yellow discolouration of and dystrophic changes in the nails, pleural effusions and lymphedema, is thought to be relatively rare; to date 44 cases have been reported. Of a further three patients with this syndrome, one had all three features, one had the yellow nails alone and the other had pleural effusions and lymphedema without classic nail changes. Each had recurrent lower respiratory tract infections; and of all 47, chronic pulmonary infections occurred in approximately one quarter and were frequently associated with chronic sinus infections. The underlying abnormality is presumed to be a congenital defect of the lymphatics, but so far this has not been demonstrated to be the cause of the nail changes, the pathogenesis of which remains obscure."} {"id": "PMID:1277062", "title": "Forty years of stress research: principal remaining problems and misconceptions.", "content": "An overview of the main problems and misconceptions in the clinical application and theoretic evaluation of the stress concept reveals that the same 10 problems appear to cause the greatest difficulties in its application, irrespective of the specialty in which it is used: (1) the correct definition of stress, stressors and the general adaptation syndrome; (2) the concept of nonspecificity in biology and medicine; (3) the conditioning of stress responses by diverse endogenous (mainly genetically determined) and exogenous (environmental) factors; (4) the relation between the genral and the local adaptation syndromes; (5) the difference between direct and indirect pathogens; (6) the definition of the morbid lesions in whose pathogenesis stress plays a particularly prominent role--the so-called diseases of adaptation; (7) the role of genetics versus that of factors under voluntary self-control in mastering biologic stress; (8) the mode of action of syntoxic and catatoxic hormones, drugs and behavioural attitudes; (9) the so-called first mediator of the stress response, which carries the message that a state of stress exists from the directly affected area to the neurohormonal regulatory centres; and (10) the prophylaxis and treatment of stress-induced damage by pharmacologic and behavioural techniques.", "contents": "Forty years of stress research: principal remaining problems and misconceptions. An overview of the main problems and misconceptions in the clinical application and theoretic evaluation of the stress concept reveals that the same 10 problems appear to cause the greatest difficulties in its application, irrespective of the specialty in which it is used: (1) the correct definition of stress, stressors and the general adaptation syndrome; (2) the concept of nonspecificity in biology and medicine; (3) the conditioning of stress responses by diverse endogenous (mainly genetically determined) and exogenous (environmental) factors; (4) the relation between the genral and the local adaptation syndromes; (5) the difference between direct and indirect pathogens; (6) the definition of the morbid lesions in whose pathogenesis stress plays a particularly prominent role--the so-called diseases of adaptation; (7) the role of genetics versus that of factors under voluntary self-control in mastering biologic stress; (8) the mode of action of syntoxic and catatoxic hormones, drugs and behavioural attitudes; (9) the so-called first mediator of the stress response, which carries the message that a state of stress exists from the directly affected area to the neurohormonal regulatory centres; and (10) the prophylaxis and treatment of stress-induced damage by pharmacologic and behavioural techniques."} {"id": "PMID:1277075", "title": "Care of the terminally ill at home.", "content": "Care of the terminally ill at home demands the attention of the medical and paramedical community. Patients who choose to remain at home while death approaches must be given full physical, emotional and psychological support by the attending physician and home care services personnel. In 1974 the Vancouver early hospital discharge home care service provided such care to 47 patients. Generally both patient and family were happy with the program. A few families were unable to cope for more than a few days but most continued the care almost to the end, a large number (14) keeping the patient at home until death occurred. Added benefits are the lower costs and the freeing of hospital beds.", "contents": "Care of the terminally ill at home. Care of the terminally ill at home demands the attention of the medical and paramedical community. Patients who choose to remain at home while death approaches must be given full physical, emotional and psychological support by the attending physician and home care services personnel. In 1974 the Vancouver early hospital discharge home care service provided such care to 47 patients. Generally both patient and family were happy with the program. A few families were unable to cope for more than a few days but most continued the care almost to the end, a large number (14) keeping the patient at home until death occurred. Added benefits are the lower costs and the freeing of hospital beds."} {"id": "PMID:1277076", "title": "A numerical method of evaluating and categorizing hospital emergency departments.", "content": "The capabilities of individual hospital emergency departments participating in an emergency medical services system must be evaluated as the first step im improving the services in the region. By means of a weighted point-scoring method, personnel, facilities, equipment and organization can be assessed and the department categorized. This not only provides an evaluation of the present status of the department but also sets standards for improvement. Categorization provides the basis for regionalization of services, whereby each department has a defined responsibility to provide treatment of specified sophistication.", "contents": "A numerical method of evaluating and categorizing hospital emergency departments. The capabilities of individual hospital emergency departments participating in an emergency medical services system must be evaluated as the first step im improving the services in the region. By means of a weighted point-scoring method, personnel, facilities, equipment and organization can be assessed and the department categorized. This not only provides an evaluation of the present status of the department but also sets standards for improvement. Categorization provides the basis for regionalization of services, whereby each department has a defined responsibility to provide treatment of specified sophistication."} {"id": "PMID:1277077", "title": "Normal-pressure hydrocephalus due to tentorial meningioma.", "content": "Normal-pressure hydrocephalus and the associated triad of dementia, apraxic gait and urinary incontinence may be casued by various, sometimes unsuspected, lesions, usually those that block the flow of cerebrospinal fluid (CSF) around the tentorium. A 58-year-old woman with insidious onset of behaviour and gait problems had occult, normal-pressure hydrocephalus and a tentorial meningioma, resection of which produced complete recovery. This case demonstrates that a distinction must be made between the syndrome of normal-pressure hydrocephalus resulting from disturbance in CSF dynamics and the pathophysiologic features of the underlying lesion.", "contents": "Normal-pressure hydrocephalus due to tentorial meningioma. Normal-pressure hydrocephalus and the associated triad of dementia, apraxic gait and urinary incontinence may be casued by various, sometimes unsuspected, lesions, usually those that block the flow of cerebrospinal fluid (CSF) around the tentorium. A 58-year-old woman with insidious onset of behaviour and gait problems had occult, normal-pressure hydrocephalus and a tentorial meningioma, resection of which produced complete recovery. This case demonstrates that a distinction must be made between the syndrome of normal-pressure hydrocephalus resulting from disturbance in CSF dynamics and the pathophysiologic features of the underlying lesion."} {"id": "PMID:1277100", "title": "Diagnosis and management of microinvasive (stage IA) carcinoma of the uterine cervix.", "content": "One hundred and sixty-two cases of Stage IA microinvasive carcinoma of the cervix are presented. These patients represent the combined experience at the University of Miami School of Medicine, Miami, Florida, and Downstate Medical Center, Brooklyn, New York. The criteria used in both institutions are 1) penetration of invasive carcinoma beneath the basement membrane of less than 1 mm and 2) absence of invasion of blood vessel or lymphatic spaces. All tissue specimens have been measured accurately by use of calibrated optics. The literature has been reviewed for criteria of diagnosis of microinvasive cancer, as well as methods of management. Our method of accurately determining depth of penetration is described and the evolution of microinvasive cancer is presented in a series of photomicrographs in which measurements are accurate to 0.1 mm. In the literature, when depth of penetration of up to 5 mm is used as criterion for microinvasive carcinoma, the incidence of nodal metastasis may be as high as 3.5%. Since, in our combined institutions, the mortality rate with radical hysterectomy is less than 1% and the incidence of ureterovaginal fistulas is 1.2%, we conclude that simple hysterectomy is not adequate therapy for lesions with stromal invasion to a depth of 5 mm.", "contents": "Diagnosis and management of microinvasive (stage IA) carcinoma of the uterine cervix. One hundred and sixty-two cases of Stage IA microinvasive carcinoma of the cervix are presented. These patients represent the combined experience at the University of Miami School of Medicine, Miami, Florida, and Downstate Medical Center, Brooklyn, New York. The criteria used in both institutions are 1) penetration of invasive carcinoma beneath the basement membrane of less than 1 mm and 2) absence of invasion of blood vessel or lymphatic spaces. All tissue specimens have been measured accurately by use of calibrated optics. The literature has been reviewed for criteria of diagnosis of microinvasive cancer, as well as methods of management. Our method of accurately determining depth of penetration is described and the evolution of microinvasive cancer is presented in a series of photomicrographs in which measurements are accurate to 0.1 mm. In the literature, when depth of penetration of up to 5 mm is used as criterion for microinvasive carcinoma, the incidence of nodal metastasis may be as high as 3.5%. Since, in our combined institutions, the mortality rate with radical hysterectomy is less than 1% and the incidence of ureterovaginal fistulas is 1.2%, we conclude that simple hysterectomy is not adequate therapy for lesions with stromal invasion to a depth of 5 mm."} {"id": "PMID:1277101", "title": "The stilbestrol-adenosis-carcinoma syndrome.", "content": "This disease complex is one of the few entirely new and previously unsuspected discoveries of the recent past. The first case, seen in 1966, ushered in an era of suspicion. A study and report on the first seven cases published in 1970 inaugurated the era of hot pursuit which culminated in 1971 in an epidemiologically structured and controlled investigation of possible etiologic factors. With the establishment of the stilbestrol association a Registry of Cases was initiated. , heralding the era of verification. This Registry, while accelerating and embossing confirmation of the suspected relationship, served an even more useful purpose by collecting under one roof and in front of one cluster of observers all the necessary and relevant data on a sufficiently large number of cases to enable rapid (1973-1974) wide dissemination of knowledge about the occurrence and behavior of the disease and its response to treatment. The behavior of these tumors is comparable to that of other cancers at this location. When they are still localized, cure is possible by either surgery or radiation therapy. Since all the individuals at risk can be identified by their clinical history, screening examination for presymptomatic cancer is entirely feasible. At the same time we can and should note the presence and nature of any morphologic anomalies of the kind, which are seen in a very high proportion of the women exposed before the 18th week of fetal life.", "contents": "The stilbestrol-adenosis-carcinoma syndrome. This disease complex is one of the few entirely new and previously unsuspected discoveries of the recent past. The first case, seen in 1966, ushered in an era of suspicion. A study and report on the first seven cases published in 1970 inaugurated the era of hot pursuit which culminated in 1971 in an epidemiologically structured and controlled investigation of possible etiologic factors. With the establishment of the stilbestrol association a Registry of Cases was initiated. , heralding the era of verification. This Registry, while accelerating and embossing confirmation of the suspected relationship, served an even more useful purpose by collecting under one roof and in front of one cluster of observers all the necessary and relevant data on a sufficiently large number of cases to enable rapid (1973-1974) wide dissemination of knowledge about the occurrence and behavior of the disease and its response to treatment. The behavior of these tumors is comparable to that of other cancers at this location. When they are still localized, cure is possible by either surgery or radiation therapy. Since all the individuals at risk can be identified by their clinical history, screening examination for presymptomatic cancer is entirely feasible. At the same time we can and should note the presence and nature of any morphologic anomalies of the kind, which are seen in a very high proportion of the women exposed before the 18th week of fetal life."} {"id": "PMID:1277102", "title": "Colposcopy.", "content": "The main clinical value of colposcopy in modern gynecology is in the clinical diagnosis of patients with abnormal cytology. In colposcopically directed biopsies it is possible for an experienced colposcopist to sample with a high degree of accuracy the most advanced histopathologic changes. This significantly decreases the frequency of diagnostic conization. Colposcopy can efficiently select patients for outpatient treatment of cervical intraepithelial neoplasia, since it precisely defines the size and localization of epithelial changes. A new application of colposcopy is in the evaluation of young girls who have been exposed to stilbestrol in utero. In these patients colposcopy can improve the diagnosis of changes in cervical-vaginal epithelium.", "contents": "Colposcopy. The main clinical value of colposcopy in modern gynecology is in the clinical diagnosis of patients with abnormal cytology. In colposcopically directed biopsies it is possible for an experienced colposcopist to sample with a high degree of accuracy the most advanced histopathologic changes. This significantly decreases the frequency of diagnostic conization. Colposcopy can efficiently select patients for outpatient treatment of cervical intraepithelial neoplasia, since it precisely defines the size and localization of epithelial changes. A new application of colposcopy is in the evaluation of young girls who have been exposed to stilbestrol in utero. In these patients colposcopy can improve the diagnosis of changes in cervical-vaginal epithelium."} {"id": "PMID:1277103", "title": "Screening techniques in endometrial cancer.", "content": "Carcinoma of the uterus is the most frequently seen malignancy of female genital tract. Screening techniques have lowered the incidence and morbidity of cervical neoplasia. Attempts to identify premalignant and silent cancers of the uterus have been made. A single diagnostic procedure has not been uniformly successful. It would appear that multiple techniques, using both cytologic and histologic material, would increase the possibility of achieving the goal of early diagnosis in uterine disease.", "contents": "Screening techniques in endometrial cancer. Carcinoma of the uterus is the most frequently seen malignancy of female genital tract. Screening techniques have lowered the incidence and morbidity of cervical neoplasia. Attempts to identify premalignant and silent cancers of the uterus have been made. A single diagnostic procedure has not been uniformly successful. It would appear that multiple techniques, using both cytologic and histologic material, would increase the possibility of achieving the goal of early diagnosis in uterine disease."} {"id": "PMID:1277104", "title": "Use of diagnostic ultrasound in trophoblastic neoplasms and ovarian tumors.", "content": "Analyses of the data on the ultrasonic diagnostic accuracies are presented for the cases of hydatidiform mole and ovarian tumors. These data are derived from two sources: the State University of New York Downstate Medical Center (SUNY-DMC) and the Chiba University School of Medicine (Chiba U.), Japan. Diagnosis of hydatidiform mole was correct in 47 (92.2%) of 51 (SUNY-DMC) and 66 (91.6%) of 72 cases (Chiba U.). The incidences of lutein cysts were 29.4% (SUNY-DMC) and 18.1%. (Chiba U.). Ultrasound plays an important role in the postmolar follow-up: increased intrauterine echoes in the subinvoluted uterus may signal a developing invasive mole or choriocarcinoma. Ultrasonic diagnoses of 223 (SUNY-DMC) and 183 (Chiba U.) ovarian tumors have been analyzed and the rates of diagnostic errors for the individual tumors are presented. Solid ovarian tumors appear to be more difficult to diagnose than cystic ovarian tumors.", "contents": "Use of diagnostic ultrasound in trophoblastic neoplasms and ovarian tumors. Analyses of the data on the ultrasonic diagnostic accuracies are presented for the cases of hydatidiform mole and ovarian tumors. These data are derived from two sources: the State University of New York Downstate Medical Center (SUNY-DMC) and the Chiba University School of Medicine (Chiba U.), Japan. Diagnosis of hydatidiform mole was correct in 47 (92.2%) of 51 (SUNY-DMC) and 66 (91.6%) of 72 cases (Chiba U.). The incidences of lutein cysts were 29.4% (SUNY-DMC) and 18.1%. (Chiba U.). Ultrasound plays an important role in the postmolar follow-up: increased intrauterine echoes in the subinvoluted uterus may signal a developing invasive mole or choriocarcinoma. Ultrasonic diagnoses of 223 (SUNY-DMC) and 183 (Chiba U.) ovarian tumors have been analyzed and the rates of diagnostic errors for the individual tumors are presented. Solid ovarian tumors appear to be more difficult to diagnose than cystic ovarian tumors."} {"id": "PMID:1277105", "title": "Pretreatment staging.", "content": "Renewed emphasis on pretreatment staging of gynecologic malignancies has resulted from a number of reports on surgical staging of malignant cervical, endometrial, and ovarian lesions. These reports have shown that by pretreatment staging, in significant numbers of patients, more advanced disease was detectable than by the usual clinical methods. From 32% to 46% of patients with stage III cervical carcicarcicarcinoma have been found to have metastatic disease in the para-aortic nodes. Diaphragmatic and para-aortic node metastases have been reported in patients with ovarian carcinoma recently in significantly higher incidences than as previously detected. The pelvic lymph nodes have been shown to be involved in 11% to 13.5% of patients with stage I endometrial carcinoma. Twelve and one-half percent had metastases to the para-aortic nodes. These data suggest the need for more accurate definition of extent of disease prior to treatment. Improvement in survival rates will not necessarily follow, but modifications in treatment must be tried.", "contents": "Pretreatment staging. Renewed emphasis on pretreatment staging of gynecologic malignancies has resulted from a number of reports on surgical staging of malignant cervical, endometrial, and ovarian lesions. These reports have shown that by pretreatment staging, in significant numbers of patients, more advanced disease was detectable than by the usual clinical methods. From 32% to 46% of patients with stage III cervical carcicarcicarcinoma have been found to have metastatic disease in the para-aortic nodes. Diaphragmatic and para-aortic node metastases have been reported in patients with ovarian carcinoma recently in significantly higher incidences than as previously detected. The pelvic lymph nodes have been shown to be involved in 11% to 13.5% of patients with stage I endometrial carcinoma. Twelve and one-half percent had metastases to the para-aortic nodes. These data suggest the need for more accurate definition of extent of disease prior to treatment. Improvement in survival rates will not necessarily follow, but modifications in treatment must be tried."} {"id": "PMID:1277108", "title": "Cryosurgery. Its use for the abnormal Pap smear.", "content": "During a two-and-one-half year period, 317 women were seen in the Colposcopy Clinic for evaluation of an abnormal Pap smear. Seventy-four (23%) desired to maintain their childbearing potential and were treated conservatively. Ten (14%) had inadequate colposcopy and underwent cold knife conization of the cervx. The remaining 64 were treated by adequate colposcopy, combined with cryosurgery; they are discussed in detail. All were managed economically as outpatients without anesthesia and no serious complications occurred. To date, only four have recurrent abnormal cervical cytology and several have delivered children. Adequate colposcopic examination combined with biopsies must proceed all cryosurgical procedures performed for abnormal cervical cytology.", "contents": "Cryosurgery. Its use for the abnormal Pap smear. During a two-and-one-half year period, 317 women were seen in the Colposcopy Clinic for evaluation of an abnormal Pap smear. Seventy-four (23%) desired to maintain their childbearing potential and were treated conservatively. Ten (14%) had inadequate colposcopy and underwent cold knife conization of the cervx. The remaining 64 were treated by adequate colposcopy, combined with cryosurgery; they are discussed in detail. All were managed economically as outpatients without anesthesia and no serious complications occurred. To date, only four have recurrent abnormal cervical cytology and several have delivered children. Adequate colposcopic examination combined with biopsies must proceed all cryosurgical procedures performed for abnormal cervical cytology."} {"id": "PMID:1277109", "title": "Pelvic exenterative therapy for gynecologic malignancy: an analysis of 70 cases.", "content": "During the 10-year period from June 1, 1965 to June 1, 1975 70 patients with gynecologic malignancy were treated with some type of pelvic exenteration at the University of Michigan Medical Center. Total pelvic exenteration was performed in over 75% of the cases. The most recent figures suggest a 3-year and 5-year survival rate of over 60%. The surgical mortality is 1.4%: the hospital mortality is 1.4%. Those patients with squamous cell disease, such as recurrent carcinoma of the cervix, vagina or vulva, have a better prognosis than do those patients with gland cell disease. Regional lymph node involvement gives a bad prognosis. Advances in therapeutic techniques during this 10-year period, including: 1) use of prophylactic antibiotics: 2) transverse abdominal incision; 3) so-called \"ski-position\" on the operating table; 4) prophylactic compartmentalization of the inferior vena cava; 5) uretero-sigmoid conduit for urinary diversion; 6) peritoneal graft as a \"lid\" over the pelvic vault' and 7) split-thickness skin graft vaginoplasty as part of the rehabilitation program, are discussed.", "contents": "Pelvic exenterative therapy for gynecologic malignancy: an analysis of 70 cases. During the 10-year period from June 1, 1965 to June 1, 1975 70 patients with gynecologic malignancy were treated with some type of pelvic exenteration at the University of Michigan Medical Center. Total pelvic exenteration was performed in over 75% of the cases. The most recent figures suggest a 3-year and 5-year survival rate of over 60%. The surgical mortality is 1.4%: the hospital mortality is 1.4%. Those patients with squamous cell disease, such as recurrent carcinoma of the cervix, vagina or vulva, have a better prognosis than do those patients with gland cell disease. Regional lymph node involvement gives a bad prognosis. Advances in therapeutic techniques during this 10-year period, including: 1) use of prophylactic antibiotics: 2) transverse abdominal incision; 3) so-called \"ski-position\" on the operating table; 4) prophylactic compartmentalization of the inferior vena cava; 5) uretero-sigmoid conduit for urinary diversion; 6) peritoneal graft as a \"lid\" over the pelvic vault' and 7) split-thickness skin graft vaginoplasty as part of the rehabilitation program, are discussed."} {"id": "PMID:1277110", "title": "Current status of the treatment of epidermoid cancer of the vulva.", "content": "Epidermoid cancer accounts for 81% of the malignancies of the vulva. Although the etiology has not been delineated, chronic vulvitis is associated with cancer in almost one-third of the patients. The staging system should utilize the most precise and accurate parameters delineated for improved treatment. A new staging system is utilized. Proven treatment is primarily surgical.", "contents": "Current status of the treatment of epidermoid cancer of the vulva. Epidermoid cancer accounts for 81% of the malignancies of the vulva. Although the etiology has not been delineated, chronic vulvitis is associated with cancer in almost one-third of the patients. The staging system should utilize the most precise and accurate parameters delineated for improved treatment. A new staging system is utilized. Proven treatment is primarily surgical."} {"id": "PMID:1277111", "title": "Clinical studies with adjunctive surgery and irradiation therapy in the treatment of carcinoma of the cervix.", "content": "The majority of patients with cancer of the cervix are treated adequately by irradiation alone, and surgery is not necessary. A role for operation developsin certain patients with Stage I-II cancer of the cervix, who are prone to develop central recurrence if treated by irradiation alone. In these patients the primary lesion is massive. The vasculature to the center of these bulky or barrel-shaped cancer is insufficient, and a population of the cancer cells, perhaps related to anoxia, is more resistant to irradiation. The postirradiation conservative hysterectomy was incorporated into the treatment plan for 212 selected patients and the number of local recurrences was reduced. Incomplete cure of the peripheral component of the disease is another mechanism of treatment failure. This may occur, even though the primary lesion is cured. Patients with cervical cancers greater than 5 cm diameter have a high incidence of node metastasis, regardless of clinical stage. In those patients with positive nodes, the standard portals for external irradiation were expanded to include nodes at higher levels. The site of metastases was established by pretreatment laparotomy and the irradiation portals were then extended to include the involved nodes. Survival rates were not improved, because recurrences were not prevented, and death from treatment complications were high.", "contents": "Clinical studies with adjunctive surgery and irradiation therapy in the treatment of carcinoma of the cervix. The majority of patients with cancer of the cervix are treated adequately by irradiation alone, and surgery is not necessary. A role for operation developsin certain patients with Stage I-II cancer of the cervix, who are prone to develop central recurrence if treated by irradiation alone. In these patients the primary lesion is massive. The vasculature to the center of these bulky or barrel-shaped cancer is insufficient, and a population of the cancer cells, perhaps related to anoxia, is more resistant to irradiation. The postirradiation conservative hysterectomy was incorporated into the treatment plan for 212 selected patients and the number of local recurrences was reduced. Incomplete cure of the peripheral component of the disease is another mechanism of treatment failure. This may occur, even though the primary lesion is cured. Patients with cervical cancers greater than 5 cm diameter have a high incidence of node metastasis, regardless of clinical stage. In those patients with positive nodes, the standard portals for external irradiation were expanded to include nodes at higher levels. The site of metastases was established by pretreatment laparotomy and the irradiation portals were then extended to include the involved nodes. Survival rates were not improved, because recurrences were not prevented, and death from treatment complications were high."} {"id": "PMID:1277112", "title": "The evolution of modern treatment of corpus cancer.", "content": "The treatment of endometrial cancer has been surgical, traditionally, with preoperative radiation gaining favor in the past three decades. This surgical treatment has been confined to simple hysterectomy and bilateral salpingo-oophorectomy in most clinics because of the pattern of spread of corpus cancer and the alleged benignity of this disease. Even now, the role of radical surgery, the timing of radiation therapy and its mode, and the place of hormonal treatment for primary disease are still the subject of discussion and clinical investigation. The definition of virulence factors and an appropriate staging dependent upon these factors has helped to clarify some of these problems and will help the analysis of cure rates when we can understand the selection of the material. With such a prospect for quality control and establishment of a protocol of individualization of treatment, we have a right to expect that appropriate surgical and radiotherapeutic measures will gain their proper priority and adjuvant hormonal therapy and chemotherapy may be incorporated.", "contents": "The evolution of modern treatment of corpus cancer. The treatment of endometrial cancer has been surgical, traditionally, with preoperative radiation gaining favor in the past three decades. This surgical treatment has been confined to simple hysterectomy and bilateral salpingo-oophorectomy in most clinics because of the pattern of spread of corpus cancer and the alleged benignity of this disease. Even now, the role of radical surgery, the timing of radiation therapy and its mode, and the place of hormonal treatment for primary disease are still the subject of discussion and clinical investigation. The definition of virulence factors and an appropriate staging dependent upon these factors has helped to clarify some of these problems and will help the analysis of cure rates when we can understand the selection of the material. With such a prospect for quality control and establishment of a protocol of individualization of treatment, we have a right to expect that appropriate surgical and radiotherapeutic measures will gain their proper priority and adjuvant hormonal therapy and chemotherapy may be incorporated."} {"id": "PMID:1277113", "title": "Current status of the treatment of gynecologic cancer by site: ovary.", "content": "Cancer of the ovary is the leading cause of death from gynecologic cancer. The constant challenge presented by ovarian cancer is that about 11,000 women die from ovarian cancer each year and the results in 1974 are no better than have been achieved in the previous two decades. Standard practice of treatment for truly invasive common epithelial ovarian cancer includes total hysterectomy, bilateral salpingo-oophorectomy, appendectomy, omentectomy, and post-surgical insertion of tubes and administration of P32 (if the disease is of limited extent). Although it is occasionally necessary to resect isolated segments of bowel, exenterative or ultraradical surgery in the management of ovarian cancer is not usually chosen because of the natural history of the disease. However, aggressive surgery is indicated not so much because it is curative, but because it potentiates other forms of treatment. All stages I through IV are treated surgically, to remove as much tumor as possible without running a risk of a gastrointestinal or genitourinary fistula. Radiation therapy has been utilized in addition to the surgical therapy in stage IV to control supraclavicular and/or inguinal node involvement. Single agent alkylating chemotherapy is chosen for the treatment of common epithelial ovarian cancers. Combination chemotherapy does not produce better results at this time, except in the treatment of embryonal tumors. The treatment of the common epithelial tumors by stage is outlined. The treatment of germ cell tumors, gonadal stromal tumors, ovarian tumors in childhood, ovarian tumors in pregnancy, as well as tumors not specific for the ovary, will also be discussed.", "contents": "Current status of the treatment of gynecologic cancer by site: ovary. Cancer of the ovary is the leading cause of death from gynecologic cancer. The constant challenge presented by ovarian cancer is that about 11,000 women die from ovarian cancer each year and the results in 1974 are no better than have been achieved in the previous two decades. Standard practice of treatment for truly invasive common epithelial ovarian cancer includes total hysterectomy, bilateral salpingo-oophorectomy, appendectomy, omentectomy, and post-surgical insertion of tubes and administration of P32 (if the disease is of limited extent). Although it is occasionally necessary to resect isolated segments of bowel, exenterative or ultraradical surgery in the management of ovarian cancer is not usually chosen because of the natural history of the disease. However, aggressive surgery is indicated not so much because it is curative, but because it potentiates other forms of treatment. All stages I through IV are treated surgically, to remove as much tumor as possible without running a risk of a gastrointestinal or genitourinary fistula. Radiation therapy has been utilized in addition to the surgical therapy in stage IV to control supraclavicular and/or inguinal node involvement. Single agent alkylating chemotherapy is chosen for the treatment of common epithelial ovarian cancers. Combination chemotherapy does not produce better results at this time, except in the treatment of embryonal tumors. The treatment of the common epithelial tumors by stage is outlined. The treatment of germ cell tumors, gonadal stromal tumors, ovarian tumors in childhood, ovarian tumors in pregnancy, as well as tumors not specific for the ovary, will also be discussed."} {"id": "PMID:1277114", "title": "Monitoring central venous pressure: principles, procedures and problems.", "content": "When caring for patients with CVP lines, nursing assessments are aided by knowledge of the interdependence of physiological factors such as cardiovascular volume and flow, cardiac efficiency and central vein capacity. Comprehension of the underlying principles facilitates adaptation of the procedure to patient needs and to the available resources.", "contents": "Monitoring central venous pressure: principles, procedures and problems. When caring for patients with CVP lines, nursing assessments are aided by knowledge of the interdependence of physiological factors such as cardiovascular volume and flow, cardiac efficiency and central vein capacity. Comprehension of the underlying principles facilitates adaptation of the procedure to patient needs and to the available resources."} {"id": "PMID:1277115", "title": "Coping with the aggressive patient: an alternative to punishment.", "content": "Extremely aggressive patients in mental institutions constitute a threat to staff and other patients that usually necessitates the use of physical restraints. With chronically aggressive patients this cycle of behaviors is defeating for both the staff and the patient. In this case history the authors describe how positive and negative reinforcement and shaping were used to alter the previously unmanageable aggression of a 36-year-old male psychiatric patient.", "contents": "Coping with the aggressive patient: an alternative to punishment. Extremely aggressive patients in mental institutions constitute a threat to staff and other patients that usually necessitates the use of physical restraints. With chronically aggressive patients this cycle of behaviors is defeating for both the staff and the patient. In this case history the authors describe how positive and negative reinforcement and shaping were used to alter the previously unmanageable aggression of a 36-year-old male psychiatric patient."} {"id": "PMID:1277116", "title": "Understanding the patient in emergency.", "content": "Psychological care should be integrated with physical care even when one works in a busy 'acute care' environment, be it an emergency department, an intensive care unit, or at the roadside as a member of the ambulance team. The quality of care is enhanced by awareness of psychological needs. Initially a conscious effort is needed to remember to have cues verified and to be open to noting subtle changes in behavior. If a continuous effort is made by each health team member, this verification process will become automatic without being time-consuming. All members of the health team must be aware that they are individuals with a multiplicity of factors affecting their thinking, feeling and behavior. They care for individuals who are also unique. A form of support proving successful with one patient may not be effective with another. Each patient must be assessed as an individual before appropriate psychological care can be effectively given. By being open to cues given by the patient and his relatives, and by having perceptions of these cues verified, an important step is taken in deciding on appropriate psychological care. With an increased awareness of the total psychological impact of the 'emergency' situation on the patient, his relatives--in fact, on the entire health team--individualized patient care will be administered in a more thorough and understanding way.", "contents": "Understanding the patient in emergency. Psychological care should be integrated with physical care even when one works in a busy 'acute care' environment, be it an emergency department, an intensive care unit, or at the roadside as a member of the ambulance team. The quality of care is enhanced by awareness of psychological needs. Initially a conscious effort is needed to remember to have cues verified and to be open to noting subtle changes in behavior. If a continuous effort is made by each health team member, this verification process will become automatic without being time-consuming. All members of the health team must be aware that they are individuals with a multiplicity of factors affecting their thinking, feeling and behavior. They care for individuals who are also unique. A form of support proving successful with one patient may not be effective with another. Each patient must be assessed as an individual before appropriate psychological care can be effectively given. By being open to cues given by the patient and his relatives, and by having perceptions of these cues verified, an important step is taken in deciding on appropriate psychological care. With an increased awareness of the total psychological impact of the 'emergency' situation on the patient, his relatives--in fact, on the entire health team--individualized patient care will be administered in a more thorough and understanding way."} {"id": "PMID:1277122", "title": "Effect of combination treatment with cyclophosphamide and nonspecific passive immunization on a transplantable tumor in WKA rats.", "content": "Combination of cyclophosphamide (CY) and passive immunization with lymphoid cells sensitized to allogeneic tumor was studied in the treatment of a methylcholanthrene-induced transplantable fibrosarcoma in WKA rats. For determination of the most effective timing of combination treatment, rats given an injection of CY on Day 3 received passive transfer of the sensitized lymphoid cells on Day 0, 1, 2, 3, 4, or 6. A remarkable therapeutic effect was observed only when the passive transfer was combined on Day 4 with CY on Day 3. Rats inoculated with tumor succumbed in all cases without any treatment. After i.v. injection of CY on Day 3, 2 of 28 rats were cured (7.1%). Passive immunization with the sensitized lymphoid cells on Day 4 resulted in no therapeutic effect. After combination of CY on Day 3 and transfer of nonsensitized normal lymphoid cells on Day 4, 2 of 15 rats survived (13.3%). However, combination of CY and passive transfer of the nonspecifically sensitized lymphoid cells resulted in 23 survivors of 29 rats (79.3%).", "contents": "Effect of combination treatment with cyclophosphamide and nonspecific passive immunization on a transplantable tumor in WKA rats. Combination of cyclophosphamide (CY) and passive immunization with lymphoid cells sensitized to allogeneic tumor was studied in the treatment of a methylcholanthrene-induced transplantable fibrosarcoma in WKA rats. For determination of the most effective timing of combination treatment, rats given an injection of CY on Day 3 received passive transfer of the sensitized lymphoid cells on Day 0, 1, 2, 3, 4, or 6. A remarkable therapeutic effect was observed only when the passive transfer was combined on Day 4 with CY on Day 3. Rats inoculated with tumor succumbed in all cases without any treatment. After i.v. injection of CY on Day 3, 2 of 28 rats were cured (7.1%). Passive immunization with the sensitized lymphoid cells on Day 4 resulted in no therapeutic effect. After combination of CY on Day 3 and transfer of nonsensitized normal lymphoid cells on Day 4, 2 of 15 rats survived (13.3%). However, combination of CY and passive transfer of the nonspecifically sensitized lymphoid cells resulted in 23 survivors of 29 rats (79.3%)."} {"id": "PMID:1277123", "title": "Comparison of in vitro methods to determine drug-induced cell lethality.", "content": "In proliferating cell populations, the inability to reproduce indefinitely is the only relevant criterion to assess cell lethality. The in vitro colony formation technique (CF) used to determine reproductive death is, however, too slow and has several technical limitations. For finding suitable, more rapid techniques that assessed drug-induced cell killing, a human lymphoma cell line was exposed in vitro to increasing concentrations of adriamycin, bleomycin, and 1,3-bis(2-chloroethyl)-1-nitrosourea for 1 hr. Survival was assayed immediately after treatment and at regular intervals thereafter. Data from CF were compared to those resulting from the following tests: doubling time, labeling index, dye exclusion, 51Cr release, and rate of [3H]thymidine uptake (scintillation index). Dye exclusion and 51Cr release failed to demonstrate any killing effect for the 3 drugs. The percentage of killing calculated from doubling time determinations, although dose dependent, failed to correlate with CF. Scintillation and labeling index values displayed similar temporal fluctuations but were not clearly dose dependent and did not correlate with CF. Thus, CF appears as the most reliable, dose-dependent index of cell lethality. Tests that measure metabolic death grossly overestimate or underestimate killing activity induced by 3 of the most effective antitumor drugs.", "contents": "Comparison of in vitro methods to determine drug-induced cell lethality. In proliferating cell populations, the inability to reproduce indefinitely is the only relevant criterion to assess cell lethality. The in vitro colony formation technique (CF) used to determine reproductive death is, however, too slow and has several technical limitations. For finding suitable, more rapid techniques that assessed drug-induced cell killing, a human lymphoma cell line was exposed in vitro to increasing concentrations of adriamycin, bleomycin, and 1,3-bis(2-chloroethyl)-1-nitrosourea for 1 hr. Survival was assayed immediately after treatment and at regular intervals thereafter. Data from CF were compared to those resulting from the following tests: doubling time, labeling index, dye exclusion, 51Cr release, and rate of [3H]thymidine uptake (scintillation index). Dye exclusion and 51Cr release failed to demonstrate any killing effect for the 3 drugs. The percentage of killing calculated from doubling time determinations, although dose dependent, failed to correlate with CF. Scintillation and labeling index values displayed similar temporal fluctuations but were not clearly dose dependent and did not correlate with CF. Thus, CF appears as the most reliable, dose-dependent index of cell lethality. Tests that measure metabolic death grossly overestimate or underestimate killing activity induced by 3 of the most effective antitumor drugs."} {"id": "PMID:1277124", "title": "Interaction of the carcinogen 3,3-dimethyl-1-phenyltriazene with nucleic acids of various rat tissues and the effect of a protein-free diet.", "content": "The methylation by 3,3-[14C]dimethyl-1-phenyltriazene of nucleic acids in various rat tissues was investigated. Following a single s.c. injection of 3,3-[14C]dimethyl-1-phenyltriazene (50 mg/kg), approximately 40% of the radioactivity was subsequently exhaled as 14CO2. Expiration of 14CO2, metabolic 14C labeling of liver proteins, and formation of 7-[14C]methylguanine, the major reaction product with nucleic acid bases, were completed within about 15 hr. Minor alkylation products detectable in DNA were O6-methylguanine and 3-methyladenine. In cytoplasmic RNA, 1-methyladenosine, 3-methylcytidine, and O6-methylguanosine were present in addition to 7-methylguanosine. Concentrations of 7-methylguanine were highest in nucleic acids of kidney and liver. Among the other organs investigated (brain, lung, spleen, small intestine), 7-methylguanine levels showed little variation but were 4 to 7 times lower than those in liver and kidney. Feeding of a protein-free diet prior to 3,3-[14C]dimethyl-1-phenyltriazene administration reduced the formation of 7-methylguanine in liver and kidney RNA, whereas in the remaining organs the extent of methylation was markedly increased. The results are discussed with respect to the significance of methylation at specific sites in nucleic acids for the initiation of malignant transformation and the possible role of 3-methyl-1-phenyltriazene as the systemically distributed proximate carcinogen of 3,3-dimethyl-1-phenyltriazene.", "contents": "Interaction of the carcinogen 3,3-dimethyl-1-phenyltriazene with nucleic acids of various rat tissues and the effect of a protein-free diet. The methylation by 3,3-[14C]dimethyl-1-phenyltriazene of nucleic acids in various rat tissues was investigated. Following a single s.c. injection of 3,3-[14C]dimethyl-1-phenyltriazene (50 mg/kg), approximately 40% of the radioactivity was subsequently exhaled as 14CO2. Expiration of 14CO2, metabolic 14C labeling of liver proteins, and formation of 7-[14C]methylguanine, the major reaction product with nucleic acid bases, were completed within about 15 hr. Minor alkylation products detectable in DNA were O6-methylguanine and 3-methyladenine. In cytoplasmic RNA, 1-methyladenosine, 3-methylcytidine, and O6-methylguanosine were present in addition to 7-methylguanosine. Concentrations of 7-methylguanine were highest in nucleic acids of kidney and liver. Among the other organs investigated (brain, lung, spleen, small intestine), 7-methylguanine levels showed little variation but were 4 to 7 times lower than those in liver and kidney. Feeding of a protein-free diet prior to 3,3-[14C]dimethyl-1-phenyltriazene administration reduced the formation of 7-methylguanine in liver and kidney RNA, whereas in the remaining organs the extent of methylation was markedly increased. The results are discussed with respect to the significance of methylation at specific sites in nucleic acids for the initiation of malignant transformation and the possible role of 3-methyl-1-phenyltriazene as the systemically distributed proximate carcinogen of 3,3-dimethyl-1-phenyltriazene."} {"id": "PMID:1277125", "title": "Fine structural changes in hepatocytes after simultaneous treatment with single doses of 3'-methyl-4-dimethylaminoazobenzene and cycloheximide.", "content": "Male rats were given single doses p.o. of 3'-methyl-4-dimethylaminoazobenzne (3'-MeDAB), either alone or at the same time as single s.c. injections of cycloheximide. They were killed either 24 or 48 hr after treatment or at intervals up to 21 months, and their hepatic tissues were examined by electron density, combined treatment with both chemicals failed to produce this acute toxic effect. However, the fine structure of the hepatic cells of rats given this combined treatment with cycloheximide and 3'-MeDAB closely resembled that obtained by chronic exposure to carcinogenic azo dyes. Of the changes thus produced, the granular endoplasmic reticulum in particular became permanently altered, both quantitatively and morphologically. Other persistent changes included mitochondrial abnormalities and glycogen depletion. Cycloheximide appears to protect the liver cell against the nonspecific acute toxic action of 3'-MeDAB, while facilitating the expression of effects that may possibly be associated with the carcinogenic action of this azo dye. Although this experimental model does not result in the appearance of tumors, it demonstrates that a single exposure to a carcinogen may induce permanent changes that are similar to those observed during carcinogenesis.", "contents": "Fine structural changes in hepatocytes after simultaneous treatment with single doses of 3'-methyl-4-dimethylaminoazobenzene and cycloheximide. Male rats were given single doses p.o. of 3'-methyl-4-dimethylaminoazobenzne (3'-MeDAB), either alone or at the same time as single s.c. injections of cycloheximide. They were killed either 24 or 48 hr after treatment or at intervals up to 21 months, and their hepatic tissues were examined by electron density, combined treatment with both chemicals failed to produce this acute toxic effect. However, the fine structure of the hepatic cells of rats given this combined treatment with cycloheximide and 3'-MeDAB closely resembled that obtained by chronic exposure to carcinogenic azo dyes. Of the changes thus produced, the granular endoplasmic reticulum in particular became permanently altered, both quantitatively and morphologically. Other persistent changes included mitochondrial abnormalities and glycogen depletion. Cycloheximide appears to protect the liver cell against the nonspecific acute toxic action of 3'-MeDAB, while facilitating the expression of effects that may possibly be associated with the carcinogenic action of this azo dye. Although this experimental model does not result in the appearance of tumors, it demonstrates that a single exposure to a carcinogen may induce permanent changes that are similar to those observed during carcinogenesis."} {"id": "PMID:1277126", "title": "Relationship between nucleolar microspherule formation by urethan and inhibition of RNA and protein synthesis.", "content": "Liver tissues of suckling C3Hf mice treated with urethan, a carcinogen and inhibitor of RNA synthesis, and with cycloheximide, an inhibitor of protein synthesis, were studied by electron microscopy and by light microscope radioautography. At 4 and 12 hr after treatment with a single dose of urethan (1 mg/g body weight). [3H]uridine incorporation in hepatocyte nuclei was 38 and 9% lower than in controls and became 32% higher at 24 hr. Nucleolar microspherules were found 1.5 and 4 hr after the treatment, increased considerably in number at 10 and 12 hr, and decreased at 24 hr. These results suggest an inverse relationship between RNA synthesis and formation of microspherules. Cycloheximide alone (3 mg/kg body weight) produced microspherules, whereas in combination with a dose of 1 or 2 mg of urethan per g body weight it partially prevented or potentiated, respectively, the microspherule production.", "contents": "Relationship between nucleolar microspherule formation by urethan and inhibition of RNA and protein synthesis. Liver tissues of suckling C3Hf mice treated with urethan, a carcinogen and inhibitor of RNA synthesis, and with cycloheximide, an inhibitor of protein synthesis, were studied by electron microscopy and by light microscope radioautography. At 4 and 12 hr after treatment with a single dose of urethan (1 mg/g body weight). [3H]uridine incorporation in hepatocyte nuclei was 38 and 9% lower than in controls and became 32% higher at 24 hr. Nucleolar microspherules were found 1.5 and 4 hr after the treatment, increased considerably in number at 10 and 12 hr, and decreased at 24 hr. These results suggest an inverse relationship between RNA synthesis and formation of microspherules. Cycloheximide alone (3 mg/kg body weight) produced microspherules, whereas in combination with a dose of 1 or 2 mg of urethan per g body weight it partially prevented or potentiated, respectively, the microspherule production."} {"id": "PMID:1277127", "title": "Two forms of thymidine kinase in normal and tumor tissues of animals.", "content": "The thymidine kinases extracted from the spleen of mice infected with Friend virus and from Yoshida sarcoma in rats were separated into two active peaks by diethylaminoethyl cellulose column chromatography, while those of normal tissues have been found to consist of only the first peak (P-1). The second peak (P-II) was also found in the enzyme from the extract of the spleen when the animals were treated by i.p. injections of 1-acetyl 2-phenylhydrazine. The two P-II peaks from tumor tissue and from spleen enlarged by anemia-inducing agents were indistinguishable on the chromatographic profile. On the other hand, the thymidine kinase extracted with Triton X-100 from a mitochondrial fraction of normal liver was found to consist of only one peak in the same position as the above P-II's on the chromatogram, but its faculty for deoxythymidine triphosphate inhibition was not identical to that of tumor tissue. This treatment with the detergent might cause dissociation of a certain component from the enzyme complex to make the extra peak (P-IIb), but it eventually shifts to P-II on the chromatogram.", "contents": "Two forms of thymidine kinase in normal and tumor tissues of animals. The thymidine kinases extracted from the spleen of mice infected with Friend virus and from Yoshida sarcoma in rats were separated into two active peaks by diethylaminoethyl cellulose column chromatography, while those of normal tissues have been found to consist of only the first peak (P-1). The second peak (P-II) was also found in the enzyme from the extract of the spleen when the animals were treated by i.p. injections of 1-acetyl 2-phenylhydrazine. The two P-II peaks from tumor tissue and from spleen enlarged by anemia-inducing agents were indistinguishable on the chromatographic profile. On the other hand, the thymidine kinase extracted with Triton X-100 from a mitochondrial fraction of normal liver was found to consist of only one peak in the same position as the above P-II's on the chromatogram, but its faculty for deoxythymidine triphosphate inhibition was not identical to that of tumor tissue. This treatment with the detergent might cause dissociation of a certain component from the enzyme complex to make the extra peak (P-IIb), but it eventually shifts to P-II on the chromatogram."} {"id": "PMID:1277128", "title": "Karyotypes of vasoformative sarcomas arising from BALB/3T3 cells attached to polycarbonate plates.", "content": "Four vasoformative sarcoma in vivo tumor lines arising from the s.c. implantation of 3 X 10(4) BALB/3T3 cells attached to a 1- X 5- X 10-mm polycarbonate platelet were shown to be quite similar in chromosome constitution to the parental 3T3 line. All tumors contained the same marker chromosomes that were present in the parent BALB/3T3 cells. The findings conclusively showed that the tumors had derived from BALB/3T3 cells and not from host cells or from the in vivo fusion of the inoculated 3T3 cells with host cells. Each tumor line had a unique karyotype that was markedly more homogeneous than that of the parental BALB/3T3 cells, strongly suggesting that each tumor represented a separate clone. An M1 marker chromosome was consistently present in each of the four tumor lines but was present in only about 50% of the parent BALB/3T3 cells; it therefore appeared to be a distinct and stable feature of the tumors.", "contents": "Karyotypes of vasoformative sarcomas arising from BALB/3T3 cells attached to polycarbonate plates. Four vasoformative sarcoma in vivo tumor lines arising from the s.c. implantation of 3 X 10(4) BALB/3T3 cells attached to a 1- X 5- X 10-mm polycarbonate platelet were shown to be quite similar in chromosome constitution to the parental 3T3 line. All tumors contained the same marker chromosomes that were present in the parent BALB/3T3 cells. The findings conclusively showed that the tumors had derived from BALB/3T3 cells and not from host cells or from the in vivo fusion of the inoculated 3T3 cells with host cells. Each tumor line had a unique karyotype that was markedly more homogeneous than that of the parental BALB/3T3 cells, strongly suggesting that each tumor represented a separate clone. An M1 marker chromosome was consistently present in each of the four tumor lines but was present in only about 50% of the parent BALB/3T3 cells; it therefore appeared to be a distinct and stable feature of the tumors."} {"id": "PMID:1277129", "title": "Correlation of antitumor chemoimmunotherapy with bone marrow macrophage precursor cell stimulation and macrophage cytotoxicity.", "content": "The present investigations have assessed the effects of prolonged cyclophosphamide (CY) and Corynebacterium (CP) treatment on the production of bone marrow macrophage precursors [colony-forming cells (CFC)] and on the cytotoxicity of macrophages comprising colonies produced by the CFC. The findings have been correlated with tumor growth in animals receiving the immunochemotherapy. In addition, studies have been directed toward ascertaining whether the administration of CP with CY might lessen the myelosuppressive effects of the latter. Following each consecutive weekly dose of CY (even after as many as 11), there was a significant depression in the number of bone marrow cells (BMC's) but, by the next injection, marrow cellularity had returned to normal. When the number of BMC's was reduced, the proportion of the remaining cells, which consisted of CFC, was increased. Upon reconstitution of the marrow, the proportion of CFC returned to the level of the controls. The total number of CFC in marrow was at no time following CY therapy significantly less than the number in marrow of untreated mice. The addition of CP to the treatment regimen with CY resulted in an absolute as well as relative increase in CFC at all times during administration of the combined therapy, i.e., when there was a depression in total numbers of marrow cells, as well as when marrow restoration had occurred. Although CP stimulated the number of cells entering into differentiation, it failed to affect the total numbers of marrow cells, as well as when marrow restoration had occurred. Although CP stimulated the number of cells entering into differentiation, it failed to affect the total BMC's had been neither increased nor prevented from decreasing, by CP administration, indicating that the use of total cellularity as an index of the CP marrow-sparing effect is without merit. The present results relative to cytotoxicity of macrophages derived from the CFC concur with and extend our previous findings indicating that the cytotoxic property of macrophages originates in its ancestral stem cell or CFC and that factors responsible for increasing the CFC population do not selectively stimulate precursor cells responsible for production of the cytotoxic macrophage. Although the proportion of cytotoxic macrophages was not altered by CP when administered with CY, the absolute number of such cells was increased. Since the increase in macrophage colony production and, consequently, in cytotoxic macrophages correlates with increased inhibition of tumor growth when CP was used with CY, it is suggested that macrophage precursors are the cells of primacy in CP immunopotentiation. Their stimulation, resulting in enhanced cytotoxic macrophage formation, could be responsible for the inhibition of tumor growth observed in our model system. The findings also suggest that when myelosuppression is a limiting factor in the use of a chemotherapeutic agent, the concomitant use of CP may be advantageous.", "contents": "Correlation of antitumor chemoimmunotherapy with bone marrow macrophage precursor cell stimulation and macrophage cytotoxicity. The present investigations have assessed the effects of prolonged cyclophosphamide (CY) and Corynebacterium (CP) treatment on the production of bone marrow macrophage precursors [colony-forming cells (CFC)] and on the cytotoxicity of macrophages comprising colonies produced by the CFC. The findings have been correlated with tumor growth in animals receiving the immunochemotherapy. In addition, studies have been directed toward ascertaining whether the administration of CP with CY might lessen the myelosuppressive effects of the latter. Following each consecutive weekly dose of CY (even after as many as 11), there was a significant depression in the number of bone marrow cells (BMC's) but, by the next injection, marrow cellularity had returned to normal. When the number of BMC's was reduced, the proportion of the remaining cells, which consisted of CFC, was increased. Upon reconstitution of the marrow, the proportion of CFC returned to the level of the controls. The total number of CFC in marrow was at no time following CY therapy significantly less than the number in marrow of untreated mice. The addition of CP to the treatment regimen with CY resulted in an absolute as well as relative increase in CFC at all times during administration of the combined therapy, i.e., when there was a depression in total numbers of marrow cells, as well as when marrow restoration had occurred. Although CP stimulated the number of cells entering into differentiation, it failed to affect the total numbers of marrow cells, as well as when marrow restoration had occurred. Although CP stimulated the number of cells entering into differentiation, it failed to affect the total BMC's had been neither increased nor prevented from decreasing, by CP administration, indicating that the use of total cellularity as an index of the CP marrow-sparing effect is without merit. The present results relative to cytotoxicity of macrophages derived from the CFC concur with and extend our previous findings indicating that the cytotoxic property of macrophages originates in its ancestral stem cell or CFC and that factors responsible for increasing the CFC population do not selectively stimulate precursor cells responsible for production of the cytotoxic macrophage. Although the proportion of cytotoxic macrophages was not altered by CP when administered with CY, the absolute number of such cells was increased. Since the increase in macrophage colony production and, consequently, in cytotoxic macrophages correlates with increased inhibition of tumor growth when CP was used with CY, it is suggested that macrophage precursors are the cells of primacy in CP immunopotentiation. Their stimulation, resulting in enhanced cytotoxic macrophage formation, could be responsible for the inhibition of tumor growth observed in our model system. The findings also suggest that when myelosuppression is a limiting factor in the use of a chemotherapeutic agent, the concomitant use of CP may be advantageous."} {"id": "PMID:1277130", "title": "Heterotopic urinary bladder with a communicating reservoir.", "content": "A heterotopic bladder attached to an Ommaya reservoir was transplanted to the back of a syngeneic rat. Following transplantation, the mucosa underwent ischemic necrosis. However, it was rapidly reepithelialized in 2 weeks as a result of spreading of the epithelium originating from the ureterotrigonal region. By light microscopy the regenerated epithelium was indistinguishable from the normal transitional epithelium, and the cannula connecting the reservoir to the bladder remained patent throughout the observation period of 22 weeks. One bladder, when examined at 22 weeks, contained a transitional cell papilloma with squamous metaplasia. Although further study is needed, this model is potentially useful in studies related to bladder carcinogenesis.", "contents": "Heterotopic urinary bladder with a communicating reservoir. A heterotopic bladder attached to an Ommaya reservoir was transplanted to the back of a syngeneic rat. Following transplantation, the mucosa underwent ischemic necrosis. However, it was rapidly reepithelialized in 2 weeks as a result of spreading of the epithelium originating from the ureterotrigonal region. By light microscopy the regenerated epithelium was indistinguishable from the normal transitional epithelium, and the cannula connecting the reservoir to the bladder remained patent throughout the observation period of 22 weeks. One bladder, when examined at 22 weeks, contained a transitional cell papilloma with squamous metaplasia. Although further study is needed, this model is potentially useful in studies related to bladder carcinogenesis."} {"id": "PMID:1277131", "title": "Developmental phase-specific alkaline phosphatase isoenzymes of human placenta and their occurrence in human cancer.", "content": "Alkaline phosphatase electrophoretic patterns characteristic of three phases in early human trophoblast development are described in this preliminary communication. Phase 1 (6 to 10 weeks) consists entirely of two heat-sensitive, L-homoarginine-inhibited bands, the slower one of which possesses antigenic determinants of live-bone-type alkaline phosphatase, whereas the fast band lacks any of the known alkaline phosphatase antigenic determinants. Phase 2 pattern (11 to 13 weeks) is that of a mixture of Phase 1 and Phase 3 isozyme components, the latter exhibiting two isozyme bands with the characteristics of term placental alkaline phosphatases correspond in order to non-Regan isoenzyme, a mixture of Regan and non-Regan isoenzymes and Regan isoenzyme in a variety of human cancer tissues. The biochemical profile characteristic of trophoblast developmental Phase 1 alkaline phosphatase is expressed as 78.5% heat-sensitive inhibition (5 min at 65 degrees), 66.3% L-homoarginine inhibition, and 17.3% L-phenylalanine inhibition where n = 12. It is hypothesized that the alkaline phosphatase of human tumor tissues reflects the expression of placental genes corresponding to one or more phases of trophoblastic development.", "contents": "Developmental phase-specific alkaline phosphatase isoenzymes of human placenta and their occurrence in human cancer. Alkaline phosphatase electrophoretic patterns characteristic of three phases in early human trophoblast development are described in this preliminary communication. Phase 1 (6 to 10 weeks) consists entirely of two heat-sensitive, L-homoarginine-inhibited bands, the slower one of which possesses antigenic determinants of live-bone-type alkaline phosphatase, whereas the fast band lacks any of the known alkaline phosphatase antigenic determinants. Phase 2 pattern (11 to 13 weeks) is that of a mixture of Phase 1 and Phase 3 isozyme components, the latter exhibiting two isozyme bands with the characteristics of term placental alkaline phosphatases correspond in order to non-Regan isoenzyme, a mixture of Regan and non-Regan isoenzymes and Regan isoenzyme in a variety of human cancer tissues. The biochemical profile characteristic of trophoblast developmental Phase 1 alkaline phosphatase is expressed as 78.5% heat-sensitive inhibition (5 min at 65 degrees), 66.3% L-homoarginine inhibition, and 17.3% L-phenylalanine inhibition where n = 12. It is hypothesized that the alkaline phosphatase of human tumor tissues reflects the expression of placental genes corresponding to one or more phases of trophoblastic development."} {"id": "PMID:1277132", "title": "Alterations in the transcriptional capacity of hepatic DNA-dependent RNA polymerase I and II by N-hydroxy-2-acetylaminofluorene.", "content": "Using hepatic RNA polymerases I and II, acetylaminofluorene modification of DNA in vitro results in reduction of RNA elongation but not in an altered frequency of incorporation of [alpha32P]ribonucleotides. In contrast, in vivo modification of RNA polymerases by a single dose of N-2-hydroxy-2-acetylaminofluorene results in an alteration of their capacity for transcribing a normal RNA product but does not affect the product size transcribed from normal or carcinogen-modified templates.", "contents": "Alterations in the transcriptional capacity of hepatic DNA-dependent RNA polymerase I and II by N-hydroxy-2-acetylaminofluorene. Using hepatic RNA polymerases I and II, acetylaminofluorene modification of DNA in vitro results in reduction of RNA elongation but not in an altered frequency of incorporation of [alpha32P]ribonucleotides. In contrast, in vivo modification of RNA polymerases by a single dose of N-2-hydroxy-2-acetylaminofluorene results in an alteration of their capacity for transcribing a normal RNA product but does not affect the product size transcribed from normal or carcinogen-modified templates."} {"id": "PMID:1277133", "title": "The effect of a growing tumor and its removal on the cytotoxicity of macrophages from cultured bone marrow cells.", "content": "Previous investigations by us have demonstrated that there is a significant but transient (4 to 14 days) increase of colony-forming cells (CFC) in bone marrow following implanation of a syngeneic mammary tumor in C3H mice. Those CFC gave rise to enhanced macrophage colony production when cultured in semisolid medium. The present studies have for the first time demonstrated that macrophages from the colonies were cytotoxic to cells from the immunizing tumor, and they continued to possess that characteristic for as long as a tumor was present in the animal from which bone marrow was derived. By 21 days after tumor removal cytotoxicity was no longer evident. The findings provide evidence to suggest that the cytotoxicity displayed by the macrophage originates in its ancestral CFC or in the antecedent stem cell. They also suggest that receptor sites of the CFC (or stem cell) that respond to a stimulus for self-replication are probably different from those sites that, when activated, result in cytotoxic properties of their progeny. The present findings also indicate not only that quantitation of macrophage production is of relevance in determining the efficacy of a therapeutic regimen but also that knowledge concerning the specific properties, i.e., ctytotoxicity, of such cells is of equal or greater importance.", "contents": "The effect of a growing tumor and its removal on the cytotoxicity of macrophages from cultured bone marrow cells. Previous investigations by us have demonstrated that there is a significant but transient (4 to 14 days) increase of colony-forming cells (CFC) in bone marrow following implanation of a syngeneic mammary tumor in C3H mice. Those CFC gave rise to enhanced macrophage colony production when cultured in semisolid medium. The present studies have for the first time demonstrated that macrophages from the colonies were cytotoxic to cells from the immunizing tumor, and they continued to possess that characteristic for as long as a tumor was present in the animal from which bone marrow was derived. By 21 days after tumor removal cytotoxicity was no longer evident. The findings provide evidence to suggest that the cytotoxicity displayed by the macrophage originates in its ancestral CFC or in the antecedent stem cell. They also suggest that receptor sites of the CFC (or stem cell) that respond to a stimulus for self-replication are probably different from those sites that, when activated, result in cytotoxic properties of their progeny. The present findings also indicate not only that quantitation of macrophage production is of relevance in determining the efficacy of a therapeutic regimen but also that knowledge concerning the specific properties, i.e., ctytotoxicity, of such cells is of equal or greater importance."} {"id": "PMID:1277134", "title": "Comparison of the products of the reaction of 7-methylbenz(a)anthracene 5,6-oxide and RNA, with those formed in 7-methylbenz(a)anthracene-treated cells.", "content": "RNA was isolated by a phenol extraction method from mouse embryo cells treated in culture with either [G-3H]-7-methylbenz(a)anthracene or [G-3H]-7-methylbenz(a)anthracene 5,6-oxide (the K-region epoxide). The RNA was degraded to ribonucleosides, mixed with ultraviolet-absorbing quantities of the epoxide ribonucleoside products isolated from RNA that had reacted with 7-methylbenz(a)anthracene 5,6-oxide in aqueous ethanol solution, and chromatographed on a column of Sephadex LH-20 eluted with a methanol:water gradient. The 7-methyl-benz(a)anthracene 5,6-oxide ribonucleoside products formed in cells were identical to those formed in aqueous solution, although the relative amounts of the products varied. The majority of these epoxide-ribonucleoside products were not identical to the products formed in cells treated with the parent hydrocarbon. These results suggest that the major reactive form of 7-methylbenz(a)anthracene that binds to RNA in mouse embryo cells is not the K-region epoxide of this hydrocarbon.", "contents": "Comparison of the products of the reaction of 7-methylbenz(a)anthracene 5,6-oxide and RNA, with those formed in 7-methylbenz(a)anthracene-treated cells. RNA was isolated by a phenol extraction method from mouse embryo cells treated in culture with either [G-3H]-7-methylbenz(a)anthracene or [G-3H]-7-methylbenz(a)anthracene 5,6-oxide (the K-region epoxide). The RNA was degraded to ribonucleosides, mixed with ultraviolet-absorbing quantities of the epoxide ribonucleoside products isolated from RNA that had reacted with 7-methylbenz(a)anthracene 5,6-oxide in aqueous ethanol solution, and chromatographed on a column of Sephadex LH-20 eluted with a methanol:water gradient. The 7-methyl-benz(a)anthracene 5,6-oxide ribonucleoside products formed in cells were identical to those formed in aqueous solution, although the relative amounts of the products varied. The majority of these epoxide-ribonucleoside products were not identical to the products formed in cells treated with the parent hydrocarbon. These results suggest that the major reactive form of 7-methylbenz(a)anthracene that binds to RNA in mouse embryo cells is not the K-region epoxide of this hydrocarbon."} {"id": "PMID:1277135", "title": "Growth of HeLa cells in diffusion chamber cultures in vivo.", "content": "In order to investigate some characteristics of Millipore diffusion chamber cultures (DCC) and their potential for the quantitation of tumor cell growth kinetics, HeLa S-3-cells were grown in diffusion chambers implanted i.p. in mice. HeLa cells grew pseudologarithmically in DCC with a population-doubling time of approximately 2.8 days when 9.2 to 12.0 X 10(5) cells were placed in the chambers initially. The population-doubling time varied as a function of the initial innocula size but was always longer than the in vitro population-doubling time of 1.2 days. Comparable harvests of cells from experiment to experiment varied quantitatively by no more than a factor 1.8. This variaton somewhat limits the use of DCC for the quantitation of subtle effects. The fate and morphology of HeLa cells in DCC were determined from scanning electron microscopy. DCC might be exploited in clinical studies of the growth of patients' tumors and the effects of various therapies in a host-mediated system.", "contents": "Growth of HeLa cells in diffusion chamber cultures in vivo. In order to investigate some characteristics of Millipore diffusion chamber cultures (DCC) and their potential for the quantitation of tumor cell growth kinetics, HeLa S-3-cells were grown in diffusion chambers implanted i.p. in mice. HeLa cells grew pseudologarithmically in DCC with a population-doubling time of approximately 2.8 days when 9.2 to 12.0 X 10(5) cells were placed in the chambers initially. The population-doubling time varied as a function of the initial innocula size but was always longer than the in vitro population-doubling time of 1.2 days. Comparable harvests of cells from experiment to experiment varied quantitatively by no more than a factor 1.8. This variaton somewhat limits the use of DCC for the quantitation of subtle effects. The fate and morphology of HeLa cells in DCC were determined from scanning electron microscopy. DCC might be exploited in clinical studies of the growth of patients' tumors and the effects of various therapies in a host-mediated system."} {"id": "PMID:1277136", "title": "Guanine-specific DNA repair after treatment of mouse skin cells with N-methyl-N'-nitro-N-nitrosoguanidine.", "content": "The incorporation of [3H]thymidine and [3H]deoxyguanosine into DNA was studied during DNA repair in mouse skin cells treated with the skin tumor initiator N-methyl-N'-nitro-N-nitrosoganidine. At high, toxic levels of N-methyl-N'-nitro-N-nitrosoguanidine, repair (incorporation of the precursor into DNA which had not replicated) was demonstrated with both precursors. At lower, less toxic doses of the carcinogen, repair could not be demonstrated with [3H]-thymidine, but it was clearly demonstrable with [3H]deoxyguanosine. Thus, we are apparently observing two kinds of DNA repair, one in which a single base (in this case, guanine) replaces a base lost by chemical or enzymatic depurination and the second in which more than one base is replaced, indicating synthesis of longer stretches DNA after extensive enzymatic excision. The guanine-specific repair shown at relatively nontoxic dose levels of N-methyl-N'-nitro-N-nitrosouanidine may be more relevant to the survival of cells than the repair demonstrated with [3H]thymidine at higher doses.", "contents": "Guanine-specific DNA repair after treatment of mouse skin cells with N-methyl-N'-nitro-N-nitrosoguanidine. The incorporation of [3H]thymidine and [3H]deoxyguanosine into DNA was studied during DNA repair in mouse skin cells treated with the skin tumor initiator N-methyl-N'-nitro-N-nitrosoganidine. At high, toxic levels of N-methyl-N'-nitro-N-nitrosoguanidine, repair (incorporation of the precursor into DNA which had not replicated) was demonstrated with both precursors. At lower, less toxic doses of the carcinogen, repair could not be demonstrated with [3H]-thymidine, but it was clearly demonstrable with [3H]deoxyguanosine. Thus, we are apparently observing two kinds of DNA repair, one in which a single base (in this case, guanine) replaces a base lost by chemical or enzymatic depurination and the second in which more than one base is replaced, indicating synthesis of longer stretches DNA after extensive enzymatic excision. The guanine-specific repair shown at relatively nontoxic dose levels of N-methyl-N'-nitro-N-nitrosouanidine may be more relevant to the survival of cells than the repair demonstrated with [3H]thymidine at higher doses."} {"id": "PMID:1277137", "title": "Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor.", "content": "Singlet oxygen, a metastable state of normal triplet oxygen, has been identified as the cytotoxic agent that is probably responsible for in vitro inactivation of TA-3 mouse mammary carcinoma cells following incorporation of hematoporphyrin and exposure to red light. This photodynamic inactivation can be completely inhibited by intracellular 1,3-diphenylisobenzofuran. This very efficient singlet oxygen trap is not toxic to the cells nor does it absorb the light responsible for hematoporphyrin activation. We have found that the singlet oxygen-trapping product, o-dibenzoylbenzene, is formed nearly quantitatively intracellularly when both the furan and hematoporphyrin are present during illumination but not when only the furan is present during illumination. The protective effect against photodynamic inactivation of the TA-3 cells afforded by 1,3-diphenylisobenzofuran coupled with the nearly quantitative formation of the singlet oxygen-trapping product indicates that singlet oxygen is the probable agent responsible for toxicity in this system.", "contents": "Identification of singlet oxygen as the cytotoxic agent in photoinactivation of a murine tumor. Singlet oxygen, a metastable state of normal triplet oxygen, has been identified as the cytotoxic agent that is probably responsible for in vitro inactivation of TA-3 mouse mammary carcinoma cells following incorporation of hematoporphyrin and exposure to red light. This photodynamic inactivation can be completely inhibited by intracellular 1,3-diphenylisobenzofuran. This very efficient singlet oxygen trap is not toxic to the cells nor does it absorb the light responsible for hematoporphyrin activation. We have found that the singlet oxygen-trapping product, o-dibenzoylbenzene, is formed nearly quantitatively intracellularly when both the furan and hematoporphyrin are present during illumination but not when only the furan is present during illumination. The protective effect against photodynamic inactivation of the TA-3 cells afforded by 1,3-diphenylisobenzofuran coupled with the nearly quantitative formation of the singlet oxygen-trapping product indicates that singlet oxygen is the probable agent responsible for toxicity in this system."} {"id": "PMID:1277138", "title": "Energetics and efficiency of photoinactivation of murine tumor cells containing hematoporphyrin.", "content": "Hematoporphryrin derivative at an intracellular concentration in TA-3 mouse mammary carcinoma cells of 0.6 or 0.9 mM required input of 3.0 X 3.6 X 10(9) quanta/cell of red light (620 nm) to achieve a 90% kill. At an intracellular concentration of 1.2 mM, this light requirement drops to 1.5 X 10(9)quanta/cell. The energy for this photodynamic process is about 100 times higher than that required for ionizing radiation to achieve the same level of kill for these cells. The quantum yield for singlet oxygen formation (the cytotoxic agent in most photodynamic processes) from hematoporphyrin derivative is 0.75 +/- 0.07 in ethanol but only 0.16 +/- 0.07 within TA-3 cells, indicating possible intracellular complexing and quenching.", "contents": "Energetics and efficiency of photoinactivation of murine tumor cells containing hematoporphyrin. Hematoporphryrin derivative at an intracellular concentration in TA-3 mouse mammary carcinoma cells of 0.6 or 0.9 mM required input of 3.0 X 3.6 X 10(9) quanta/cell of red light (620 nm) to achieve a 90% kill. At an intracellular concentration of 1.2 mM, this light requirement drops to 1.5 X 10(9)quanta/cell. The energy for this photodynamic process is about 100 times higher than that required for ionizing radiation to achieve the same level of kill for these cells. The quantum yield for singlet oxygen formation (the cytotoxic agent in most photodynamic processes) from hematoporphyrin derivative is 0.75 +/- 0.07 in ethanol but only 0.16 +/- 0.07 within TA-3 cells, indicating possible intracellular complexing and quenching."} {"id": "PMID:1277139", "title": "Effect of avitaminosis A and hypervitaminosis A on urinary bladder carcinogenicity of N-(4-(5-Nitro-2-furyl)-2-thiazolyl)formamide.", "content": "The effect of vitamin A deficiency and hypervitaminosis A on the urothelial carcinogenicity of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formanmide (FANFT) was determined in female weanling Sprague-Dawley rats. Vitamin A deficiency resulted in squamous metaplasia of the urinary bladder and high incidences of cystitis, ureteritis, and pyelonephritis. Administration of FANFT to vitamin A-deficient rats appeared to accelerate the carcinogenic process, with earlier appearance of urinary bladder tumors and the development of ureteral and renal pelvic carcinomas. Most of these tumors were squamous cell, occasionally with transitional cell foci. Hypervitaminosis A prevented the appearance of squamous metaplasia and squamous cell neoplasia in rats fed FANFT, but it did not inhibit the formation of transitional cell hyperplasia or neoplasia in comparison to rats receiving normal levels of vitamin A and FANFT.", "contents": "Effect of avitaminosis A and hypervitaminosis A on urinary bladder carcinogenicity of N-(4-(5-Nitro-2-furyl)-2-thiazolyl)formamide. The effect of vitamin A deficiency and hypervitaminosis A on the urothelial carcinogenicity of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formanmide (FANFT) was determined in female weanling Sprague-Dawley rats. Vitamin A deficiency resulted in squamous metaplasia of the urinary bladder and high incidences of cystitis, ureteritis, and pyelonephritis. Administration of FANFT to vitamin A-deficient rats appeared to accelerate the carcinogenic process, with earlier appearance of urinary bladder tumors and the development of ureteral and renal pelvic carcinomas. Most of these tumors were squamous cell, occasionally with transitional cell foci. Hypervitaminosis A prevented the appearance of squamous metaplasia and squamous cell neoplasia in rats fed FANFT, but it did not inhibit the formation of transitional cell hyperplasia or neoplasia in comparison to rats receiving normal levels of vitamin A and FANFT."} {"id": "PMID:1277140", "title": "Distribution and disposition of platinum following intravenous administration of cis-diamminedichloroplatinum(II) (NSC 119875) to dogs.", "content": "cis-Diamminedichloroplatinum(II) is an antineoplastic drug that is undergoing a renewed clinical interest as a drug for use in combination regimens. In order to increase the understanding of the pharmacokinetics of this drug, the plasma clearance and organ distribution of platinum were followed in female beagle dogs treated with a single i.v. dose of cis-diamminedichloroplatinum(II). Plasma levels of platinum were determined by flameless atomic absorption spectrometry and showed a distinctly biphasic clearance pattern with a rapid-phase half-time of considerably less than 1 hr and a slow-phase half-time of nearly 5 days. During the first 4 hr after treatment, plasma levels fell by 90% while 60 to 70% of the applied dose was recovered in the urine. Sixteen tissues plus plasma, bile, and urine were routinely analyzed for platinum content. An easily measurable plasma concentration of platinum was still detectable 12 days after treatment, with no significant change in plasma concentration between Days 4 and 12. Initial concentrations of platinum were highest in organs of excretion, gonads, spleen, and adrenals but remained significantly elevated only in kidney, liver, ovary, and uterus, where a tissue: plasma ratio of 3 to 4 was maintained for as long as 6 days posttreatment. The apparent in vitro binding of platinum to dog plasma and to bovine serum albumin was studied by ultrafiltration and increased progressively during 48 hr of incubation at 37 degrees.", "contents": "Distribution and disposition of platinum following intravenous administration of cis-diamminedichloroplatinum(II) (NSC 119875) to dogs. cis-Diamminedichloroplatinum(II) is an antineoplastic drug that is undergoing a renewed clinical interest as a drug for use in combination regimens. In order to increase the understanding of the pharmacokinetics of this drug, the plasma clearance and organ distribution of platinum were followed in female beagle dogs treated with a single i.v. dose of cis-diamminedichloroplatinum(II). Plasma levels of platinum were determined by flameless atomic absorption spectrometry and showed a distinctly biphasic clearance pattern with a rapid-phase half-time of considerably less than 1 hr and a slow-phase half-time of nearly 5 days. During the first 4 hr after treatment, plasma levels fell by 90% while 60 to 70% of the applied dose was recovered in the urine. Sixteen tissues plus plasma, bile, and urine were routinely analyzed for platinum content. An easily measurable plasma concentration of platinum was still detectable 12 days after treatment, with no significant change in plasma concentration between Days 4 and 12. Initial concentrations of platinum were highest in organs of excretion, gonads, spleen, and adrenals but remained significantly elevated only in kidney, liver, ovary, and uterus, where a tissue: plasma ratio of 3 to 4 was maintained for as long as 6 days posttreatment. The apparent in vitro binding of platinum to dog plasma and to bovine serum albumin was studied by ultrafiltration and increased progressively during 48 hr of incubation at 37 degrees."} {"id": "PMID:1277141", "title": "Comparative adduct formation of 4-aminobiphenyl and 2-aminofluorene derivatives with macromolecules of isolated liver parenchymal cells.", "content": "Isolated parenchymal cells of rat liver have been used in a study of the metabolic activation of derivatives of the carcinogens 4-aminobiphenyl and 2-aminofluorene. The formation of adducts of these compounds with cellular RNA and protein has been taken as evidence of their transformation to metabolites that are capable of spontaneous reaction with tissue macromolecules. The hydroxamic acid N-hydroxy-N-4-acetylaminobiphenyl was bound to RNA to a greater extent than were the amino-, hydroxylamino-, nitroso-, nitro-, acetylamino-, or azoxybiphenyl derivatives. RNA adducts of the hydroxamic acid retained little of the acetyl group. The structural requirements for binding and the nature of the bound derivatives are consistent with the activation of N-hydroxy-N-4-acetylaminobiphenyl by N leads to O acyltransfer. Approximately equal quantities of 4-nitrosobiphenyl and the hydroxamic acid were bound to protein, but far less of the nitroso derivative was incorporated into RNA. Adduct formation of N-hydroxy-N-2-acetylaminofluorene with RNA occurred with retention of the acetyl group and was dependent on the concentration of sulfate in the media. Consequently, reaction of the fluorenyl derivative with RNA probably resulted from conjugation of the hydroxamic acid with sulfate.", "contents": "Comparative adduct formation of 4-aminobiphenyl and 2-aminofluorene derivatives with macromolecules of isolated liver parenchymal cells. Isolated parenchymal cells of rat liver have been used in a study of the metabolic activation of derivatives of the carcinogens 4-aminobiphenyl and 2-aminofluorene. The formation of adducts of these compounds with cellular RNA and protein has been taken as evidence of their transformation to metabolites that are capable of spontaneous reaction with tissue macromolecules. The hydroxamic acid N-hydroxy-N-4-acetylaminobiphenyl was bound to RNA to a greater extent than were the amino-, hydroxylamino-, nitroso-, nitro-, acetylamino-, or azoxybiphenyl derivatives. RNA adducts of the hydroxamic acid retained little of the acetyl group. The structural requirements for binding and the nature of the bound derivatives are consistent with the activation of N-hydroxy-N-4-acetylaminobiphenyl by N leads to O acyltransfer. Approximately equal quantities of 4-nitrosobiphenyl and the hydroxamic acid were bound to protein, but far less of the nitroso derivative was incorporated into RNA. Adduct formation of N-hydroxy-N-2-acetylaminofluorene with RNA occurred with retention of the acetyl group and was dependent on the concentration of sulfate in the media. Consequently, reaction of the fluorenyl derivative with RNA probably resulted from conjugation of the hydroxamic acid with sulfate."} {"id": "PMID:1277142", "title": "Effect of 6-hydroxydopamine on tumor growth.", "content": "The growth of C-1300 neuroblastoma was markedly slowed in 6-hydroxydopamine-treated mice. The growth of the A-10 breast adenocarcinoma was also significantly retarded in 6-hydroxydopamine-treated mice but the growth of B-16 melanoma was not affected. In mice axotomized by pretreatment with 6-hydroxydopamine, the growth of C-1300 neuroblastoma was slowed but the growth of the A-10 tumor was not affected. It is suggested that an intact functional sympathetic nervous system may be a factor that determines the rate of growth of certain tumors in vivo.", "contents": "Effect of 6-hydroxydopamine on tumor growth. The growth of C-1300 neuroblastoma was markedly slowed in 6-hydroxydopamine-treated mice. The growth of the A-10 breast adenocarcinoma was also significantly retarded in 6-hydroxydopamine-treated mice but the growth of B-16 melanoma was not affected. In mice axotomized by pretreatment with 6-hydroxydopamine, the growth of C-1300 neuroblastoma was slowed but the growth of the A-10 tumor was not affected. It is suggested that an intact functional sympathetic nervous system may be a factor that determines the rate of growth of certain tumors in vivo."} {"id": "PMID:1277143", "title": "Alteration of mammalian cells by interaction with artificial lipid vesicles.", "content": "Artificial lipid vesicles interact with a variety of mammalian cells, including blood cells, spleen cells, and tumor cells, and during this interaction components can be transferred from the vesicle to the cell and from the cell to the vesicle. Transfer of intravesicular material is observed when artificial lipid vesicles carrying an intravesicular marker, 99mTc (as TcO4- ion), are incubated with mammalian cells. When vesicles prepared with [14C] phospholipid are incubated with mammalian cells, the labeled lipid is also transferable to mammalian cells. Conversely, if the mammalian cell surface is radiolabeled (with 125I), the cell marker is in part transferable to the vesicles. Thus, interaction of mammalian cells with vesicles alters the characteristics of the cell in several ways. There is a loss of some cell surface components, a gain of vesicle lipid components, and an acquisition of intravesicular contents. Such alteration may affect the biological behavior of the cell in vivo. Thus, the in vivo distribution in the mouse of isologous red blood cells is altered after interaction with vesicles; the liver and spleen remove large proportions of such cells in comparison to control erythrocytes labeled with 51Cr. The behavior of vesicle survivors from a cell interaction is also altered. Upon reexposure of such vesicles to a fresh population of cells, the intravesicular marker is no longer transferable to cells; and upon injection of such vesicles into mice, the liver accumulation of vesicular label is reduced as compared with that of nonincubated vesicles.", "contents": "Alteration of mammalian cells by interaction with artificial lipid vesicles. Artificial lipid vesicles interact with a variety of mammalian cells, including blood cells, spleen cells, and tumor cells, and during this interaction components can be transferred from the vesicle to the cell and from the cell to the vesicle. Transfer of intravesicular material is observed when artificial lipid vesicles carrying an intravesicular marker, 99mTc (as TcO4- ion), are incubated with mammalian cells. When vesicles prepared with [14C] phospholipid are incubated with mammalian cells, the labeled lipid is also transferable to mammalian cells. Conversely, if the mammalian cell surface is radiolabeled (with 125I), the cell marker is in part transferable to the vesicles. Thus, interaction of mammalian cells with vesicles alters the characteristics of the cell in several ways. There is a loss of some cell surface components, a gain of vesicle lipid components, and an acquisition of intravesicular contents. Such alteration may affect the biological behavior of the cell in vivo. Thus, the in vivo distribution in the mouse of isologous red blood cells is altered after interaction with vesicles; the liver and spleen remove large proportions of such cells in comparison to control erythrocytes labeled with 51Cr. The behavior of vesicle survivors from a cell interaction is also altered. Upon reexposure of such vesicles to a fresh population of cells, the intravesicular marker is no longer transferable to cells; and upon injection of such vesicles into mice, the liver accumulation of vesicular label is reduced as compared with that of nonincubated vesicles."} {"id": "PMID:1277144", "title": "Chemically induced smooth muscle tumors of the mouse urinary bladder.", "content": "Occasional submucosal tumors of indeterminate origin and without definite connection to the overlying mucosa have been reported in mice given various carcinogenic agents. Two Swiss mice fed niridazole developed such tumors. Electron microscopy of 1 of the tumors revealed thin myofilaments with oval dense bodies, marginal dense plaques, and gap junctions, identifying the tumor as originating from smooth muscle cells. No desmosomes, tonofilaments, secretory granules, striated muscle, or collagen were present in the tumor cells. Since the biology of these lesions is unknown, classification as benign or malignant cannot be made at this time. Their recognition is important in evaluating possible bladder carcinogens in mice.", "contents": "Chemically induced smooth muscle tumors of the mouse urinary bladder. Occasional submucosal tumors of indeterminate origin and without definite connection to the overlying mucosa have been reported in mice given various carcinogenic agents. Two Swiss mice fed niridazole developed such tumors. Electron microscopy of 1 of the tumors revealed thin myofilaments with oval dense bodies, marginal dense plaques, and gap junctions, identifying the tumor as originating from smooth muscle cells. No desmosomes, tonofilaments, secretory granules, striated muscle, or collagen were present in the tumor cells. Since the biology of these lesions is unknown, classification as benign or malignant cannot be made at this time. Their recognition is important in evaluating possible bladder carcinogens in mice."} {"id": "PMID:1277145", "title": "The effects of prolonged feeding with aflatoxin B1 on adult rat liver.", "content": "The effects of feeding adult rats for 6 weeks with a carcinogenic regimen of aflatoxin-contaminated diet are described. Effects on the histological appearance of liver sections are related to changes observed in nuclear separations carried out using zonal centrifugation. Changes in the levels of nuclear RNA and DNA synthesis have been studied in the populations of hepatic nuclei separated in the zonal rotor. The first 3 weeks of the feeding period was accompanied by continuing inhibitions of nucleic acid synthesis, terminating in a loss of the majority of the tetraploid hepatocyte nuclear population. The subsequent 3 weeks of feeding was predominantly a period of proliferation, restoration of the lobular architecture, and recovery of nucleic acid-synthetic activity. The possible bases of these two opposite effects, inhibition followed by stimulation, which occurred sequentially during the continued feeding of the toxic diet, are discussed.", "contents": "The effects of prolonged feeding with aflatoxin B1 on adult rat liver. The effects of feeding adult rats for 6 weeks with a carcinogenic regimen of aflatoxin-contaminated diet are described. Effects on the histological appearance of liver sections are related to changes observed in nuclear separations carried out using zonal centrifugation. Changes in the levels of nuclear RNA and DNA synthesis have been studied in the populations of hepatic nuclei separated in the zonal rotor. The first 3 weeks of the feeding period was accompanied by continuing inhibitions of nucleic acid synthesis, terminating in a loss of the majority of the tetraploid hepatocyte nuclear population. The subsequent 3 weeks of feeding was predominantly a period of proliferation, restoration of the lobular architecture, and recovery of nucleic acid-synthetic activity. The possible bases of these two opposite effects, inhibition followed by stimulation, which occurred sequentially during the continued feeding of the toxic diet, are discussed."} {"id": "PMID:1277146", "title": "The metabolism of rhodium(II) acetate in tumor-bearing mice.", "content": "Rhodium(II) acetate has been shown to have carcinostatic activity in Swiss mice bearing Ehrlich ascites tumors. For metabolic studies, single therapeutic doses of rhodium(II) [1-14C]acetate that had been given i.p. implantations 3 days previously of 50-fold 10(6) Ehrlich ascites tumor cells. The tissue distribution and excretion of the rhodium (measured by atomic absorption spectrometry) and the acetate (measured by 14C label) were followed at designated time intervals up to 24 hr after injection. Rhodium(II) acetate, a neutral cage complex, breaks down to rhodium and acetate ionic species within 2 hr after i.p. injection, as measured by the rapid exhalation of 14CO2. Both the rhodium and 14C label disappear rapidly from the ascites fluid, with a small but variable amount of each species being incorporated into the tumor cells. Both species were detected mainly in the blood plasma, and the primary organ of deposition was the liver. No measurable quantity of rhodium was found in the brain tissue. During the first 24 hr following drug administration, only 5% rhodium was eliminated in the urine.", "contents": "The metabolism of rhodium(II) acetate in tumor-bearing mice. Rhodium(II) acetate has been shown to have carcinostatic activity in Swiss mice bearing Ehrlich ascites tumors. For metabolic studies, single therapeutic doses of rhodium(II) [1-14C]acetate that had been given i.p. implantations 3 days previously of 50-fold 10(6) Ehrlich ascites tumor cells. The tissue distribution and excretion of the rhodium (measured by atomic absorption spectrometry) and the acetate (measured by 14C label) were followed at designated time intervals up to 24 hr after injection. Rhodium(II) acetate, a neutral cage complex, breaks down to rhodium and acetate ionic species within 2 hr after i.p. injection, as measured by the rapid exhalation of 14CO2. Both the rhodium and 14C label disappear rapidly from the ascites fluid, with a small but variable amount of each species being incorporated into the tumor cells. Both species were detected mainly in the blood plasma, and the primary organ of deposition was the liver. No measurable quantity of rhodium was found in the brain tissue. During the first 24 hr following drug administration, only 5% rhodium was eliminated in the urine."} {"id": "PMID:1277147", "title": "Estimation of tumor growth fraction in murine tumors by the primer-available DNA-dependent DNA polymerase assay.", "content": "The tumor growth fraction measured by the percentage labeled mitoses method has been determined in transplantable solid and ascites murine tumors, the latter being measured at different times after transplantation. These values were compared to an in vitro, autoradiographic assay that determines the fraction of cells in a given population (primer-available DNA-dependent DNA polymerase index) that have both nuclear DNA-dependent DNA polymerase and DNA capable of acting as primer-template. It appears that almost all cells with a short G1 phase duration (less than 19 hr) that are within the proliferative cycle are primer-available DNA-dependent DNA polymerase positive. The results of the comparison indicate that the primer-available DNA-dependent DNA polymerase index estimation of growth fraction is very nearly identical to the growth fraction measured by the percentage labeled mitoses method.", "contents": "Estimation of tumor growth fraction in murine tumors by the primer-available DNA-dependent DNA polymerase assay. The tumor growth fraction measured by the percentage labeled mitoses method has been determined in transplantable solid and ascites murine tumors, the latter being measured at different times after transplantation. These values were compared to an in vitro, autoradiographic assay that determines the fraction of cells in a given population (primer-available DNA-dependent DNA polymerase index) that have both nuclear DNA-dependent DNA polymerase and DNA capable of acting as primer-template. It appears that almost all cells with a short G1 phase duration (less than 19 hr) that are within the proliferative cycle are primer-available DNA-dependent DNA polymerase positive. The results of the comparison indicate that the primer-available DNA-dependent DNA polymerase index estimation of growth fraction is very nearly identical to the growth fraction measured by the percentage labeled mitoses method."} {"id": "PMID:1277148", "title": "Covalent interaction of metabolites of the carcinogen trichloroethylene in rat hepatic microsomes.", "content": "Trichloroethylene (TCE), a structural analog of vinyl chloride, is known to induce hepatocellular carcinoma and other tumors in C57BL/6 X C3H/He F1 (hereafter known as B6C3F1) hybrid mice. TCE epoxide, a possible metabolite, is expected to be highly reactive toward cellular nucleophiles, e.g., proteins and nucleic acids. Hence, the microsomal metabolism of TCE and its covalent binding to microsomal protein were examined. Rat liver microsomes were incubated in vitro with [14C]TCE. The results showed that TCE binds covalently to microsomal protein since extensive organic extractions and Pronase digestion do not dissociate the TCE-protein complex. The binding was decreased by 7,8-benzoflavone, blocked by SKF-525A, and enhanced by i.p. administration of phenobarbital. The possibility that TCE epoxide, once formed, could be converted to water-soluble products through enzymatic hydrolysis by epoxide hydrase was also investigated. Addition of 3,3,3-trichloropropene oxide, a potent inhibitor of epoxide hydrase, to the incubation system markedly enhanced the binding of TCE. These observations support the view that, in order to bind to protein, it is necessary for TCE to be metabolized to its epoxide, a reactive intermediate that is most likely involved in TCE carcinogenesis and toxicity.", "contents": "Covalent interaction of metabolites of the carcinogen trichloroethylene in rat hepatic microsomes. Trichloroethylene (TCE), a structural analog of vinyl chloride, is known to induce hepatocellular carcinoma and other tumors in C57BL/6 X C3H/He F1 (hereafter known as B6C3F1) hybrid mice. TCE epoxide, a possible metabolite, is expected to be highly reactive toward cellular nucleophiles, e.g., proteins and nucleic acids. Hence, the microsomal metabolism of TCE and its covalent binding to microsomal protein were examined. Rat liver microsomes were incubated in vitro with [14C]TCE. The results showed that TCE binds covalently to microsomal protein since extensive organic extractions and Pronase digestion do not dissociate the TCE-protein complex. The binding was decreased by 7,8-benzoflavone, blocked by SKF-525A, and enhanced by i.p. administration of phenobarbital. The possibility that TCE epoxide, once formed, could be converted to water-soluble products through enzymatic hydrolysis by epoxide hydrase was also investigated. Addition of 3,3,3-trichloropropene oxide, a potent inhibitor of epoxide hydrase, to the incubation system markedly enhanced the binding of TCE. These observations support the view that, in order to bind to protein, it is necessary for TCE to be metabolized to its epoxide, a reactive intermediate that is most likely involved in TCE carcinogenesis and toxicity."} {"id": "PMID:1277149", "title": "Pulmonary carcinogenesis by derivatives of polynuclear aromatic alkylating agents.", "content": "Simple alkylating derivatives of polycyclic aromatic hydrocarbons have been found to be much more carcinogenic in the Strain A mouse than are the parent hydrocarbons. It has also been shown that the carcinogenicity of these halomethyl hydrocarbons is not a function of the first-order solvolysis rate. The acridine antitumor agent and mutagen ICR 170, 2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]acridine dihydrochloride, has been shown to be a potent carcinogen in the same system when administered i.v., superseding data in the literature indicating inactivity when the drug is administered i.p. Stimulation of the immune system has been shown to have a marked inhibitory effect on the carcinogenic activity of this compound.", "contents": "Pulmonary carcinogenesis by derivatives of polynuclear aromatic alkylating agents. Simple alkylating derivatives of polycyclic aromatic hydrocarbons have been found to be much more carcinogenic in the Strain A mouse than are the parent hydrocarbons. It has also been shown that the carcinogenicity of these halomethyl hydrocarbons is not a function of the first-order solvolysis rate. The acridine antitumor agent and mutagen ICR 170, 2-methoxy-6-chloro-9-[3-(ethyl-2-chloroethyl)aminopropylamino]acridine dihydrochloride, has been shown to be a potent carcinogen in the same system when administered i.v., superseding data in the literature indicating inactivity when the drug is administered i.p. Stimulation of the immune system has been shown to have a marked inhibitory effect on the carcinogenic activity of this compound."} {"id": "PMID:1277150", "title": "Molecular structures of the chemical carcinogens 7-chloromethylbenz(a)anthracene and 7-chloromethyl-12-methylbenz(a)anthracene.", "content": "The three-dimensional structures of two carcinogens, 7-chloromethyl-12-methylbenz[a]anthracene and 7-chloromethylbenz[ai1anthracene, have been determined by X-ray crystallographic techniques. Both compounds are carcinogenic and are believed to act by alkylating DNA. However, the first has a nonplanar ring system, whereas the second has a planar ring system. The nonplanarity of 7-chloromethyl-12-methylbenz[a]anthracene results from steric hindrance between a hydrogen atom of the 12-methyl group and a hydrogen atom on the [a] ring. This molecule cannot be made planar unless the 12-methyl group or the [a] ring is removed. It is concluded that the carcinogenic activity of these compounds does not correlate with planarity of the ring system. This implies that, if DNA is the critical target of attack by these carcinogens, complete intercalation of the aromatic ring system of the carcinogen between the bases of DNA is not a likely mechanism of carcinogenic action in this system of compounds. The results presented here and those of others are more consistent with a model for a common interaction of the carcinogens 7-chloromethyl-12-methylbenz[a]anthracene and 7-chloromethylbenz[a]anthracene with DNA, in which they alkylate the bases of DNA and then lie with their long axes approximately parallel to the helix axis, probably in the major groove.", "contents": "Molecular structures of the chemical carcinogens 7-chloromethylbenz(a)anthracene and 7-chloromethyl-12-methylbenz(a)anthracene. The three-dimensional structures of two carcinogens, 7-chloromethyl-12-methylbenz[a]anthracene and 7-chloromethylbenz[ai1anthracene, have been determined by X-ray crystallographic techniques. Both compounds are carcinogenic and are believed to act by alkylating DNA. However, the first has a nonplanar ring system, whereas the second has a planar ring system. The nonplanarity of 7-chloromethyl-12-methylbenz[a]anthracene results from steric hindrance between a hydrogen atom of the 12-methyl group and a hydrogen atom on the [a] ring. This molecule cannot be made planar unless the 12-methyl group or the [a] ring is removed. It is concluded that the carcinogenic activity of these compounds does not correlate with planarity of the ring system. This implies that, if DNA is the critical target of attack by these carcinogens, complete intercalation of the aromatic ring system of the carcinogen between the bases of DNA is not a likely mechanism of carcinogenic action in this system of compounds. The results presented here and those of others are more consistent with a model for a common interaction of the carcinogens 7-chloromethyl-12-methylbenz[a]anthracene and 7-chloromethylbenz[a]anthracene with DNA, in which they alkylate the bases of DNA and then lie with their long axes approximately parallel to the helix axis, probably in the major groove."} {"id": "PMID:1277151", "title": "Elevation of dihydrofolate reductase, thymidylate synthetase, and thymidine kinase in cultured mammalian cells after exposure to folate antagonists.", "content": "Roswell Park Memorial Institute 4265 human lymphoblasts were grown with three dihydrofolate reductase inhibitors: a 2,4-diaminopteridine, methotrexate; a 2,4-diaminoquinazoline, chlorasquin; and, a 2,4-diaminotriazine, triazinate. In the absence of inhibitor, dihydrofolate reductase activity increased to a peak at mid-log growth and then declined during the later growth stages. When cells were grown with 10(-8) M antifolate, cell growth was not affected, but dihydrofolate reductase activity (assayed at pH 7.0) remained at approximately initial levels throughout the growth cycle. This represented 60 to 70% less activity at the mid-log stage of growth, as compared to control cells. Dihydrofolate reductase activity in cells grown with 10(-8) M methotrexate, when assayed at pH 8.5, reached levels twice those in control cells. Enzyme activity in cells grown with 10(-8) M chlorasquin, when assayed at pH 8.5, was also higher than at pH 7.0, but it was not as high as that observed in methotrexate-treated cells. Activity in cells grown with 10(-8) M triazinate was approximately the same when assayed at either pH 7.0 or 8.5. At 10(-8) M, the three antifolates had no effect on the activities of thymidylate synthetase, thymidine kinase, serine trans-hydroxymethylase, 5,10-methylenetetrahydrofolate dehydrogenase, 10-formyltetrahydrofolate synthetase, and thymidylate kinase. However, when concentrations were used which completely inhibited growth (10(-7) to 10(-5) M methotrexate or chlorasuin; 10(-6) to 10(-5) M triazinate), dihydrofolate reductase was progressively inhibited, and there was a two- and a threefold elevation of thymidylate synthetase and thymidine kinase activity, respectively. Quantitatively, the elevation of either enzyme was similar over the range of growth-inhibitory concentrations studied. The activities of the other enzymes were unaffected. Methotrexate and chlorasquin inhibited thymidylate synthetase in a noncompetitive manner (with respect to 5,10-methylenetetrahydrofolate) with approximate Ki values of 4.5 X 10(-5) M and 4.9 X 10(-6) M, respectively. Triazinate, at 10(-3) M, had no significant effect on thymidylate synthetase activity. At 10(-3) M, the antifolates produced a negligible inhibition of thymidine kinase. Deoxyuridine 5'-monophosphate (10(-5) M) effectively protected thymidylate synthetase from heat inactivation in vitro. Dihydrofolate or 5,10-methylenetetrahydrofolate, at 10(-3) M, only partially protected thymidylate synthetase. Concentrations of methotrexate (10(-7) to 10(-6) M), chlorasquin (10(-7) M), and triazinate (10(-6) to 10(-5) M), which produced thymidylate synthetase elevation in vivo, did not protect the enzyme from heat inactivation in vitro. Methotrexate at 10(-5) M and chlorasquin at 10(-6) M gave slight protection. Thymidine kinase was stabilized only by thymidine.", "contents": "Elevation of dihydrofolate reductase, thymidylate synthetase, and thymidine kinase in cultured mammalian cells after exposure to folate antagonists. Roswell Park Memorial Institute 4265 human lymphoblasts were grown with three dihydrofolate reductase inhibitors: a 2,4-diaminopteridine, methotrexate; a 2,4-diaminoquinazoline, chlorasquin; and, a 2,4-diaminotriazine, triazinate. In the absence of inhibitor, dihydrofolate reductase activity increased to a peak at mid-log growth and then declined during the later growth stages. When cells were grown with 10(-8) M antifolate, cell growth was not affected, but dihydrofolate reductase activity (assayed at pH 7.0) remained at approximately initial levels throughout the growth cycle. This represented 60 to 70% less activity at the mid-log stage of growth, as compared to control cells. Dihydrofolate reductase activity in cells grown with 10(-8) M methotrexate, when assayed at pH 8.5, reached levels twice those in control cells. Enzyme activity in cells grown with 10(-8) M chlorasquin, when assayed at pH 8.5, was also higher than at pH 7.0, but it was not as high as that observed in methotrexate-treated cells. Activity in cells grown with 10(-8) M triazinate was approximately the same when assayed at either pH 7.0 or 8.5. At 10(-8) M, the three antifolates had no effect on the activities of thymidylate synthetase, thymidine kinase, serine trans-hydroxymethylase, 5,10-methylenetetrahydrofolate dehydrogenase, 10-formyltetrahydrofolate synthetase, and thymidylate kinase. However, when concentrations were used which completely inhibited growth (10(-7) to 10(-5) M methotrexate or chlorasuin; 10(-6) to 10(-5) M triazinate), dihydrofolate reductase was progressively inhibited, and there was a two- and a threefold elevation of thymidylate synthetase and thymidine kinase activity, respectively. Quantitatively, the elevation of either enzyme was similar over the range of growth-inhibitory concentrations studied. The activities of the other enzymes were unaffected. Methotrexate and chlorasquin inhibited thymidylate synthetase in a noncompetitive manner (with respect to 5,10-methylenetetrahydrofolate) with approximate Ki values of 4.5 X 10(-5) M and 4.9 X 10(-6) M, respectively. Triazinate, at 10(-3) M, had no significant effect on thymidylate synthetase activity. At 10(-3) M, the antifolates produced a negligible inhibition of thymidine kinase. Deoxyuridine 5'-monophosphate (10(-5) M) effectively protected thymidylate synthetase from heat inactivation in vitro. Dihydrofolate or 5,10-methylenetetrahydrofolate, at 10(-3) M, only partially protected thymidylate synthetase. Concentrations of methotrexate (10(-7) to 10(-6) M), chlorasquin (10(-7) M), and triazinate (10(-6) to 10(-5) M), which produced thymidylate synthetase elevation in vivo, did not protect the enzyme from heat inactivation in vitro. Methotrexate at 10(-5) M and chlorasquin at 10(-6) M gave slight protection. Thymidine kinase was stabilized only by thymidine."} {"id": "PMID:1277154", "title": "Kinetic response of human lymphoid cells to adriamycin-DNA complex in vitro.", "content": "The lysosomotropic agent adriamycin-DNA complex was analyzed for its effect on cell cycle progression of human lymphoid cells in culture by means of pulse cytophotometry. Complexing to DNA slightly reduced the perturbation effects previously reported for adriamycin alone. The major kinetic response was a G2 block, the magnitude and duration of which was dependent on drug concentration and duration of treatment. When high drug concentrations were maintained for a prolonged period of time, an additional, completely reversible block in G1 phase or at the G1-S boundary was observed, accounting for two-step G2 accumulation curves. Cell age markedly influenced the magnitude of G2 accumulation in that treatment of cells in S and early G2 phase was most effective.", "contents": "Kinetic response of human lymphoid cells to adriamycin-DNA complex in vitro. The lysosomotropic agent adriamycin-DNA complex was analyzed for its effect on cell cycle progression of human lymphoid cells in culture by means of pulse cytophotometry. Complexing to DNA slightly reduced the perturbation effects previously reported for adriamycin alone. The major kinetic response was a G2 block, the magnitude and duration of which was dependent on drug concentration and duration of treatment. When high drug concentrations were maintained for a prolonged period of time, an additional, completely reversible block in G1 phase or at the G1-S boundary was observed, accounting for two-step G2 accumulation curves. Cell age markedly influenced the magnitude of G2 accumulation in that treatment of cells in S and early G2 phase was most effective."} {"id": "PMID:1277156", "title": "Morphological and clinical observations of patients with early bladder cancer treated with total cystectomy.", "content": "In 21 cases, early bladder cancer was detected by urine cytology, although not by cystoscopy, and was treated by total cystectomy. The neoplasms, all transitional cell carcinomas of moderate to high degrees of anaplasia, were entirely in situ in 17 of the 21 patients; in 4, although mainly in situ, the tumors showed additional minimal microinvasion. Widespread mucosal involvement was demonstrated in every case by step-sectioning, and extension into the prostatic ducts occurred in 7 of the 19 male patients and into the mucosa of one or both distal ureters in 12 patients. Premalignant atypia of the mucosa was also widespread and direct intramucosal spread of cancer cells was a significant factor, particularly along the prostatic ducts and ureters. The duration of significant symptoms (follow-up for 9 years before cystectomy in several cases and for 8 years in 1 histologically proved case) suggests that the evolution of these tumors may be considerably longer than previously documented.", "contents": "Morphological and clinical observations of patients with early bladder cancer treated with total cystectomy. In 21 cases, early bladder cancer was detected by urine cytology, although not by cystoscopy, and was treated by total cystectomy. The neoplasms, all transitional cell carcinomas of moderate to high degrees of anaplasia, were entirely in situ in 17 of the 21 patients; in 4, although mainly in situ, the tumors showed additional minimal microinvasion. Widespread mucosal involvement was demonstrated in every case by step-sectioning, and extension into the prostatic ducts occurred in 7 of the 19 male patients and into the mucosa of one or both distal ureters in 12 patients. Premalignant atypia of the mucosa was also widespread and direct intramucosal spread of cancer cells was a significant factor, particularly along the prostatic ducts and ureters. The duration of significant symptoms (follow-up for 9 years before cystectomy in several cases and for 8 years in 1 histologically proved case) suggests that the evolution of these tumors may be considerably longer than previously documented."} {"id": "PMID:1277157", "title": "Membrane changes during urothelial hyperplasia and neoplasia.", "content": "Normal mammalian urothelium has a complex pattern of morphogenesis and cell differentiation. The luminal face of the polyploid, superficial cells is limited by a morphologically unique plasma membrane with a highly ordered substructure. This membrane is a convenient marker for normal differentiation in the urothelium. In reversible, benign hyperplasia, following cytotoxic damage, the luminal face of the most superficial layer of cells is limited by an undifferentiated membrane which is comparable to the plasma membrane of normal basal cells. When the hyperplasia regresses, normal differentiation of the urothelium is reestablished, and the normal, specialized surface membrane is again produced. In both preneoplastic hyperplasia and early neoplasia induced by various carcinogenic regimens, a novel form of differentiation affecting the surface membrane is seen in some superficial cells. Microvilli form on their free luminal face and are limited by a membrane with an unusual, structured glycocalyx, which is not found in normal urothelium or benign hyperplasia. This glycocalyx also develops on some cells in transitional cell carcinoma of the bladder in man. This novel glycocalyx may be a morphological marker for neoplastic transformation in the urothelium.", "contents": "Membrane changes during urothelial hyperplasia and neoplasia. Normal mammalian urothelium has a complex pattern of morphogenesis and cell differentiation. The luminal face of the polyploid, superficial cells is limited by a morphologically unique plasma membrane with a highly ordered substructure. This membrane is a convenient marker for normal differentiation in the urothelium. In reversible, benign hyperplasia, following cytotoxic damage, the luminal face of the most superficial layer of cells is limited by an undifferentiated membrane which is comparable to the plasma membrane of normal basal cells. When the hyperplasia regresses, normal differentiation of the urothelium is reestablished, and the normal, specialized surface membrane is again produced. In both preneoplastic hyperplasia and early neoplasia induced by various carcinogenic regimens, a novel form of differentiation affecting the surface membrane is seen in some superficial cells. Microvilli form on their free luminal face and are limited by a membrane with an unusual, structured glycocalyx, which is not found in normal urothelium or benign hyperplasia. This glycocalyx also develops on some cells in transitional cell carcinoma of the bladder in man. This novel glycocalyx may be a morphological marker for neoplastic transformation in the urothelium."} {"id": "PMID:1277158", "title": "Early lesions in experimental bladder cancer: experimental design and light microscopic findings.", "content": "N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT) fed to male and female Fischer rats at a dose of 0.2% of the diet induces lesions of the urinary bladder which progress from mild hyperplasia at 2 to 4 weeks, to moderate hyperplasia at 6 to 8 weeks, severe nodular and papillary hyperplasia at 10 to 14 weeks, and microinvasive carcinomas by 25 weeks as observed by light microscopy. Male Fischer rats fed FANFT for 2 to 4 weeks and then maintained on control diet show regression of the bladder lesions within 2 weeks to normal-appearing mucosa which persists through 50 weeks. Rats fed FANFT for 6 weeks show regression of the moderately hyperplastic epithelium to normal within 4 weeks after being placed on control diet which persists through 50 weeks. Rats fed FANFT for 8 to 10 weeks show regression of the hyperplastic bladder epithelium within 2 weeks of receiving control diet, but focal areas of mild hyperplasia are detectable through the 20th week of the experiment. By the 50th week the rats fed FANFT for 8 weeks all had moderate to marked hyperplasia, but the rats fed FANFT for 10 weeks had transitional cell tumors, one of which was invasive through the entire thickness of the bladder wall. The lesions present in rats fed FANFT for 12, 14, or 20 weeks continued to progress to invasive tumors (microinvasive or invasion of muscle) after the rats had been maintained on control diet through 50 weeks. Thus, the hyperplastic lesions developing through 6 weeks of FANFT administration appear to be reversible if FANFT is discontinued, but later lesions appear to be irreversible.", "contents": "Early lesions in experimental bladder cancer: experimental design and light microscopic findings. N-[4-(5-Nitro-2-furyl)-2-thiazolyl]formamide (FANFT) fed to male and female Fischer rats at a dose of 0.2% of the diet induces lesions of the urinary bladder which progress from mild hyperplasia at 2 to 4 weeks, to moderate hyperplasia at 6 to 8 weeks, severe nodular and papillary hyperplasia at 10 to 14 weeks, and microinvasive carcinomas by 25 weeks as observed by light microscopy. Male Fischer rats fed FANFT for 2 to 4 weeks and then maintained on control diet show regression of the bladder lesions within 2 weeks to normal-appearing mucosa which persists through 50 weeks. Rats fed FANFT for 6 weeks show regression of the moderately hyperplastic epithelium to normal within 4 weeks after being placed on control diet which persists through 50 weeks. Rats fed FANFT for 8 to 10 weeks show regression of the hyperplastic bladder epithelium within 2 weeks of receiving control diet, but focal areas of mild hyperplasia are detectable through the 20th week of the experiment. By the 50th week the rats fed FANFT for 8 weeks all had moderate to marked hyperplasia, but the rats fed FANFT for 10 weeks had transitional cell tumors, one of which was invasive through the entire thickness of the bladder wall. The lesions present in rats fed FANFT for 12, 14, or 20 weeks continued to progress to invasive tumors (microinvasive or invasion of muscle) after the rats had been maintained on control diet through 50 weeks. Thus, the hyperplastic lesions developing through 6 weeks of FANFT administration appear to be reversible if FANFT is discontinued, but later lesions appear to be irreversible."} {"id": "PMID:1277159", "title": "Early lesions in experimental bladder cancer: scanning electron microscopy of cell surface markers.", "content": "The administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) at a dose of 0.2% of the diet to male Fischer rats results in the appearance of urinary bladder epithelial lesions progressing from hyperplasia to invasive transitional cell carcinomas. These progressive epithelial alterations have been observed by scanning electron microscopy at 2-week intervals with special attention paid to cells covering the luminal surface. After 2 to 4 weeks of FANFT administration there is mild pleomorphism and moderate swelling of the surface cells giving a cobblestone appearance. The normal pattern of microridges of superficial transitional cells is still present, although occasional cells by 4 weeks of FANFT feeding are covered by small uniform microvilli. By 6 weeks these changes are more extensive and more cells are covered with uniform microvilli. By 8 weeks, cells covered with pleomorphic microvilli are found in discrete foci, and by 10 weeks nodular or papillary lesions are present. The 2- and 4-week lesions regress to normal within 2 to 4 weeks of discontinuing FANFT administration, and the 6- and 8-week lesions regress toward normal in 4 to 6 weeks of being fed control diet. The 6-week lesions have regressed entirely to normal 44 weeks after FANFT was stopped, but the 8-week lesions have progressed to moderate or marked hyperplastic lesions by 42 weeks of control diet with pleomorphic cells covered with pleomorphic microvilli. The results of this study suggest that lesions are reversible up to and including 6 weeks of 0.2% FANFT in the diet, and that, by 8 weeks of 0.2% FANFT, irreversible lesions result which do not revert to normal after 42 weeks of control diet.", "contents": "Early lesions in experimental bladder cancer: scanning electron microscopy of cell surface markers. The administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT) at a dose of 0.2% of the diet to male Fischer rats results in the appearance of urinary bladder epithelial lesions progressing from hyperplasia to invasive transitional cell carcinomas. These progressive epithelial alterations have been observed by scanning electron microscopy at 2-week intervals with special attention paid to cells covering the luminal surface. After 2 to 4 weeks of FANFT administration there is mild pleomorphism and moderate swelling of the surface cells giving a cobblestone appearance. The normal pattern of microridges of superficial transitional cells is still present, although occasional cells by 4 weeks of FANFT feeding are covered by small uniform microvilli. By 6 weeks these changes are more extensive and more cells are covered with uniform microvilli. By 8 weeks, cells covered with pleomorphic microvilli are found in discrete foci, and by 10 weeks nodular or papillary lesions are present. The 2- and 4-week lesions regress to normal within 2 to 4 weeks of discontinuing FANFT administration, and the 6- and 8-week lesions regress toward normal in 4 to 6 weeks of being fed control diet. The 6-week lesions have regressed entirely to normal 44 weeks after FANFT was stopped, but the 8-week lesions have progressed to moderate or marked hyperplastic lesions by 42 weeks of control diet with pleomorphic cells covered with pleomorphic microvilli. The results of this study suggest that lesions are reversible up to and including 6 weeks of 0.2% FANFT in the diet, and that, by 8 weeks of 0.2% FANFT, irreversible lesions result which do not revert to normal after 42 weeks of control diet."} {"id": "PMID:1277160", "title": "Changes in plasma membrane structure associated with malignant transformation in human urinary bladder epithelium.", "content": "Integral membrane proteins are visualized as intramembrane particles (IMP; also called membrane-associated particles) at the cleaved surfaces of freeze-fractured plasma membranes. Topographical distributions of the IMP of urothelial cell membranes in normal human bladder and for a small series of low-grade noninvasive transitional cell carcinomas and invasive transtional cell carcinomas are shown to be significantly different. Using several statistical methods that test IMP topography via \u00e0 vis the random (Poisson) hypothesis, it is demonstrated that IMP are mildly aggregated in plasma membranes of normal human urothelial cells and that, in noninvasive carcinomas, IMP aggregation is increased. In invasive transitional cell carcinomas, IMP are statistically nonaggregated and are in a random distribution in the plane of the membrane. IMP numerical densities are also altered in the course of neoplastic transformation. IMP are significantly increased in number in plasma membranes in human noninvasive transitional cell carcinomas but are similar to control values in invasive tumors. Loss of IMP and changes in IMP topography may be related to tumor invasiveness or they may represent an epiphenomenon.", "contents": "Changes in plasma membrane structure associated with malignant transformation in human urinary bladder epithelium. Integral membrane proteins are visualized as intramembrane particles (IMP; also called membrane-associated particles) at the cleaved surfaces of freeze-fractured plasma membranes. Topographical distributions of the IMP of urothelial cell membranes in normal human bladder and for a small series of low-grade noninvasive transitional cell carcinomas and invasive transtional cell carcinomas are shown to be significantly different. Using several statistical methods that test IMP topography via \u00e0 vis the random (Poisson) hypothesis, it is demonstrated that IMP are mildly aggregated in plasma membranes of normal human urothelial cells and that, in noninvasive carcinomas, IMP aggregation is increased. In invasive transitional cell carcinomas, IMP are statistically nonaggregated and are in a random distribution in the plane of the membrane. IMP numerical densities are also altered in the course of neoplastic transformation. IMP are significantly increased in number in plasma membranes in human noninvasive transitional cell carcinomas but are similar to control values in invasive tumors. Loss of IMP and changes in IMP topography may be related to tumor invasiveness or they may represent an epiphenomenon."} {"id": "PMID:1277161", "title": "Organ culture of normal and carcinogen-treated rat bladder.", "content": "A system for organ culture of rat bladder in defined medium, without serum, is described. Transitional epithelial morphology of normal bladder was well maintained in Waymouth's Medium MB 752/1, while Ham's Medium F12 caused marked epithelial hyperplasia. Hyperplastic epithelial states induced by in vivo administration of the carcinogen, N-methyl-N-nitrosourea, were well maintained in vitro during organ culture in Medium MB 752/1. The combination of hydrocortisone and insulin markedly inhibited the proliferative response of normal bladder epithelium grown in Medium F12.", "contents": "Organ culture of normal and carcinogen-treated rat bladder. A system for organ culture of rat bladder in defined medium, without serum, is described. Transitional epithelial morphology of normal bladder was well maintained in Waymouth's Medium MB 752/1, while Ham's Medium F12 caused marked epithelial hyperplasia. Hyperplastic epithelial states induced by in vivo administration of the carcinogen, N-methyl-N-nitrosourea, were well maintained in vitro during organ culture in Medium MB 752/1. The combination of hydrocortisone and insulin markedly inhibited the proliferative response of normal bladder epithelium grown in Medium F12."} {"id": "PMID:1277164", "title": "Sequential phenotypic changes in hyperplastic areas during hepatocarcinogenesis in the rat.", "content": "Sequential phenotypic changes in hyperplastic areas of rat liver during N-2-fluorenylacetamide feeding were studied by enzyme and immunohistochemical methods combined with radioautography. Hyperplastic area showed a marked deficiency of beta-glucuronidase and serine dehydratase during their developing phase, the 6th through the 9th experimental weeks, and were fairly specifically labeled by injections of tritiated thymidine after partial hepatectomy performed at the 9th week. A sequential observation on these labeled hyperplastic areas revealed a considerable elevation of the levels of these marker enzymes in the majority of the labeled areas in 3 to 18 weeks after labeling. On the other hand, there was a small group of hyperplastic areas in which the enzyme deficiency persisted during the observation period. This type of lesion was generally larger than those showing enzymic maturation. Labeled cells were not detectable either in distinct hyperplastic nodules at late phase or in carcinomas. The metabolic regulation in the cells comprising hyperplastic areas was studied by checking the induction and repression of serine dehydratase after dietary stimuli. Serine dehydratase was not inducible in hyperplastic areas during the developing phase or in areas with persistent enzyme deficiency, but it was clearly induced and repressed in areas where there was an elevation of the endogenous enzyme level. The areas of hyperplasia with persistent enzyme deficiency and growth appeared to be more important than the ones of phenotypic maturation in relation to the later development of carcinoma. The phenotypic maturation in hyperplastic areas might represent reversion of altered cells towards normalcy from the condition related with neoplastic transformation.", "contents": "Sequential phenotypic changes in hyperplastic areas during hepatocarcinogenesis in the rat. Sequential phenotypic changes in hyperplastic areas of rat liver during N-2-fluorenylacetamide feeding were studied by enzyme and immunohistochemical methods combined with radioautography. Hyperplastic area showed a marked deficiency of beta-glucuronidase and serine dehydratase during their developing phase, the 6th through the 9th experimental weeks, and were fairly specifically labeled by injections of tritiated thymidine after partial hepatectomy performed at the 9th week. A sequential observation on these labeled hyperplastic areas revealed a considerable elevation of the levels of these marker enzymes in the majority of the labeled areas in 3 to 18 weeks after labeling. On the other hand, there was a small group of hyperplastic areas in which the enzyme deficiency persisted during the observation period. This type of lesion was generally larger than those showing enzymic maturation. Labeled cells were not detectable either in distinct hyperplastic nodules at late phase or in carcinomas. The metabolic regulation in the cells comprising hyperplastic areas was studied by checking the induction and repression of serine dehydratase after dietary stimuli. Serine dehydratase was not inducible in hyperplastic areas during the developing phase or in areas with persistent enzyme deficiency, but it was clearly induced and repressed in areas where there was an elevation of the endogenous enzyme level. The areas of hyperplasia with persistent enzyme deficiency and growth appeared to be more important than the ones of phenotypic maturation in relation to the later development of carcinoma. The phenotypic maturation in hyperplastic areas might represent reversion of altered cells towards normalcy from the condition related with neoplastic transformation."} {"id": "PMID:1277165", "title": "Cytology and cytogenesis of neoplastic (hyperplastic) hepatic nodules.", "content": "Cytochemical and electron microscopic investigations of neoplastic nodules induced in the rat liver by nitrosomorpholine or thioacetamide show that most neoplastic nodules are comprised of a rather heterogeneous cell population. At least four different types of altered hepatocytes can be distinguished: (a) \"clear\" glycogen storage cells with a dislocation and relative reduction of the granular endoplasmic reticulum; (b) \"acidophilic\" glycogen storage cells with a hypertrophy of the agranular endoplasmic reticulum; (c) fat-storing cells; and (d) basophilic cells poor in glycogen and rich in ribosomes. In addition, there are diverse intermediate cell types. The cytochemically demonstrable activity of glucose-6-phosphatase is reduced in most neoplastic nodules, but it may also be normal or even increased. The clear and the acidophilic cells precede the development of the neoplastic nodules by weeks and months. They usually form foci which are taken to be preneoplastic lesions. During the formation of neoplastic nodules and hepatocellular carcinomas originating for such foci the glycogen of the clear and the acidophilic cells is progressively reduced, whereas the number of ribosomes (basophilia) increases. This process, which may be accompanied by a transitory accumulation of fat, leads to the evolution of basophilic carcinoma cells. We conclude from these observations that the majority of the neoplastic nodules consist of a mixture of precancerous, definitely cancerous, and diverse intermediate cells. Neoplastic nodules in which basophilic cells prevail may already be carcinomas. Although the neoplastic nodules seem to be a frequent precursor of hepatocellular carcinomas, the latter may also develop without going through the nodule stage.", "contents": "Cytology and cytogenesis of neoplastic (hyperplastic) hepatic nodules. Cytochemical and electron microscopic investigations of neoplastic nodules induced in the rat liver by nitrosomorpholine or thioacetamide show that most neoplastic nodules are comprised of a rather heterogeneous cell population. At least four different types of altered hepatocytes can be distinguished: (a) \"clear\" glycogen storage cells with a dislocation and relative reduction of the granular endoplasmic reticulum; (b) \"acidophilic\" glycogen storage cells with a hypertrophy of the agranular endoplasmic reticulum; (c) fat-storing cells; and (d) basophilic cells poor in glycogen and rich in ribosomes. In addition, there are diverse intermediate cell types. The cytochemically demonstrable activity of glucose-6-phosphatase is reduced in most neoplastic nodules, but it may also be normal or even increased. The clear and the acidophilic cells precede the development of the neoplastic nodules by weeks and months. They usually form foci which are taken to be preneoplastic lesions. During the formation of neoplastic nodules and hepatocellular carcinomas originating for such foci the glycogen of the clear and the acidophilic cells is progressively reduced, whereas the number of ribosomes (basophilia) increases. This process, which may be accompanied by a transitory accumulation of fat, leads to the evolution of basophilic carcinoma cells. We conclude from these observations that the majority of the neoplastic nodules consist of a mixture of precancerous, definitely cancerous, and diverse intermediate cells. Neoplastic nodules in which basophilic cells prevail may already be carcinomas. Although the neoplastic nodules seem to be a frequent precursor of hepatocellular carcinomas, the latter may also develop without going through the nodule stage."} {"id": "PMID:1277166", "title": "Sequential phenotypic and biochemical alterations during chemical hepatocarcinogenesis.", "content": "Chronic exposure to chemical carcinogens induces in the target tissue a series of complex morphological and biochemical alterations that precede the appearance of overt cancer. Three types of experiments are described: (a) exposure of livers that had received subcarcinogenic doses of N-2-fluorenylacetamide to a subcarcinogenic dose of dimethylnitrosamine resulted in a 100% yield of neoplastic nodules and hepatocellular carcinoma: (b) neither normal hepatocytes nor those obtained from neoplastic nodules were agglutinated by any of the lectins tested. This finding was also true for slowly growing cells from carcinomas, while those of rapidly growing carcinomas were agglutinated by several lectins; (c) analysis of nonhistone proteins isolated from neoplastic nodules demonstrated the appearance of many new species in euchromatin when compared with normal liver. Carcinomas demonstrated an even greater number of new species and they were demonstrated in heterochromatin as well.", "contents": "Sequential phenotypic and biochemical alterations during chemical hepatocarcinogenesis. Chronic exposure to chemical carcinogens induces in the target tissue a series of complex morphological and biochemical alterations that precede the appearance of overt cancer. Three types of experiments are described: (a) exposure of livers that had received subcarcinogenic doses of N-2-fluorenylacetamide to a subcarcinogenic dose of dimethylnitrosamine resulted in a 100% yield of neoplastic nodules and hepatocellular carcinoma: (b) neither normal hepatocytes nor those obtained from neoplastic nodules were agglutinated by any of the lectins tested. This finding was also true for slowly growing cells from carcinomas, while those of rapidly growing carcinomas were agglutinated by several lectins; (c) analysis of nonhistone proteins isolated from neoplastic nodules demonstrated the appearance of many new species in euchromatin when compared with normal liver. Carcinomas demonstrated an even greater number of new species and they were demonstrated in heterochromatin as well."} {"id": "PMID:1277167", "title": "Preneoplastic lesions of the human mammary gland transplanted into the nude athymic mouse.", "content": "Morphologically normal lobules and atypical lobules postulated precancerous to ductal carcinoma were transplanted to test their biological behavior. Supravital staining disclosed the 1 to 4-mm microorgans. \"Cleared\" mammary fat pads of nude mice were optimal transplantation sites. Of the total of 217 transplants from 19 cancer-associated and 13 non-cancer-associated breast, 151 survived after 2 to 27 weeks. Of 61 surviving normal-appearing lobules from cancer-associated breasts transplanted without prior in vitro maintenance, 20 (30%) dedifferentiated, and of 48 surviving lobules from noncancerous breasts, 11 (20%) dedifferentiated. Fifteen of 28 histologically normal-appearing lobules (60%) obtained from cancer-associated breasts after age 50 dedifferentiated. Thirty of 36 atypical lobules isolated from the breast tissue were obtained from cancer-associated breasts and the 5 of those that dedifferentiated came from cancer-associated breasts. Twenty of 22 (90%) dedifferentiating transplants from cancer-associated breasts showed a vascularization response, whereas 3 of 7 (43%) from noncancer-associated breasts did so. If dedifferentiation in this experimental setting is indicative of a precancerous potential, the data on normal-appearing lobules obtained from cancer-associated breasts from women over age 50 suggest that these lobules carry the greatest precancerous potential. Such lobules probably belong to a type persisting after menopause and they may be hormonally autonomous. Such lobules might undergo further atypia in vivo and, eventually, cancerous transformation.", "contents": "Preneoplastic lesions of the human mammary gland transplanted into the nude athymic mouse. Morphologically normal lobules and atypical lobules postulated precancerous to ductal carcinoma were transplanted to test their biological behavior. Supravital staining disclosed the 1 to 4-mm microorgans. \"Cleared\" mammary fat pads of nude mice were optimal transplantation sites. Of the total of 217 transplants from 19 cancer-associated and 13 non-cancer-associated breast, 151 survived after 2 to 27 weeks. Of 61 surviving normal-appearing lobules from cancer-associated breasts transplanted without prior in vitro maintenance, 20 (30%) dedifferentiated, and of 48 surviving lobules from noncancerous breasts, 11 (20%) dedifferentiated. Fifteen of 28 histologically normal-appearing lobules (60%) obtained from cancer-associated breasts after age 50 dedifferentiated. Thirty of 36 atypical lobules isolated from the breast tissue were obtained from cancer-associated breasts and the 5 of those that dedifferentiated came from cancer-associated breasts. Twenty of 22 (90%) dedifferentiating transplants from cancer-associated breasts showed a vascularization response, whereas 3 of 7 (43%) from noncancer-associated breasts did so. If dedifferentiation in this experimental setting is indicative of a precancerous potential, the data on normal-appearing lobules obtained from cancer-associated breasts from women over age 50 suggest that these lobules carry the greatest precancerous potential. Such lobules probably belong to a type persisting after menopause and they may be hormonally autonomous. Such lobules might undergo further atypia in vivo and, eventually, cancerous transformation."} {"id": "PMID:1277168", "title": "Angiogenic capacity of preneoplastic lesions of the murine mammary gland as a marker of neoplastic transformation.", "content": "The angiogenic capacity of normal, preneoplastic, and neoplastic murine mammary tissues from high-tumor-incidence strains (C3H, C3H-AVV, C3H-AVVfB) was compared by implanting small biopsies on the iris surface in New Zealand White rabbits. Proliferation of iris blood vessels was studied by: (a) in vivo slit-lamp stereomicroscopy and fluorescein angiography; (b) colloidal carbon injection of the microvasculature; and (c) histological examination. Ninety % of mammary tumor implants elicited neovascular changes after 48 to 72 hr, regardless of their histological classification or the presence or absence of mammary tumor virus. Corticosteroid treatment did not abolish this response. In contrast, only 6% of implants from normal mammary glands caused any vasoproliferation. Thirty % of implants from premalignant hyperplastic alveolar nodules produced a pattern of vessel growth similar to tumor implants. D-2 line (hyperplastic alveolar nodule outgrowth) tissues, which have a high predicted tumor incidence, induced significantly more neovascular responses (p less than 0.002) than do morphologically and biochemically similar D-1 line tissues, which have a low predicted tumor incidence. These data suggest that angiogenic capacity is expressed during the malignant progression of murine mammary tissues; this property may provide a means for identifying those preneoplastic tissues that are most at risk for cancer.", "contents": "Angiogenic capacity of preneoplastic lesions of the murine mammary gland as a marker of neoplastic transformation. The angiogenic capacity of normal, preneoplastic, and neoplastic murine mammary tissues from high-tumor-incidence strains (C3H, C3H-AVV, C3H-AVVfB) was compared by implanting small biopsies on the iris surface in New Zealand White rabbits. Proliferation of iris blood vessels was studied by: (a) in vivo slit-lamp stereomicroscopy and fluorescein angiography; (b) colloidal carbon injection of the microvasculature; and (c) histological examination. Ninety % of mammary tumor implants elicited neovascular changes after 48 to 72 hr, regardless of their histological classification or the presence or absence of mammary tumor virus. Corticosteroid treatment did not abolish this response. In contrast, only 6% of implants from normal mammary glands caused any vasoproliferation. Thirty % of implants from premalignant hyperplastic alveolar nodules produced a pattern of vessel growth similar to tumor implants. D-2 line (hyperplastic alveolar nodule outgrowth) tissues, which have a high predicted tumor incidence, induced significantly more neovascular responses (p less than 0.002) than do morphologically and biochemically similar D-1 line tissues, which have a low predicted tumor incidence. These data suggest that angiogenic capacity is expressed during the malignant progression of murine mammary tissues; this property may provide a means for identifying those preneoplastic tissues that are most at risk for cancer."} {"id": "PMID:1277169", "title": "Prophylaxis of early preneoplastic lesions of the mammary gland.", "content": "Daily treatment (for 12 to 14 months) of 2-month-old nulliparous or 8-month-old multiparous C3H/HeJ mice with 0.1 mg of 2-bromo-alpha-ergocryptine (CB-154) or 6-methyl-8-beta-ergoline-acetonitrile, efficacious inhibitors of prolactin secretion, markedly reduced the incidence of spontaneous mammary hyperplastic nodules and mammary tumors. CB-154 appeared to be more effective than 6-methyl-8-beta-ergoline-acetonitrile in suppressing the incidence of mammary tumors; the ergot virtually prevented the appearance of mammary tumors in nulliparous mice. Daily treatment of 5-month-old estrogen-treated, ovariectomized-hysterectomized C3H/HeJ mice for 12 months with CB-154 also significantly reduced the incidence of hyperplastic nodules and mammary tumors when compared with ovariectomized-hysterectomized mice treated with steroid alone. Daily treatment of multiparous C3H/HeJ mammary tumor-bearing mice with CB-154 or 6-methyl-8-beta-ergoline-acetonitrile generally failed, however, to promote regression of the mammary tumors. Thus significant prophylaxis of early preneoplastic lesions by drug-induced hormone (prolactin) suppression, resulting in a marked reduction in mammary tumor incidence, has been demonstrated in this study.", "contents": "Prophylaxis of early preneoplastic lesions of the mammary gland. Daily treatment (for 12 to 14 months) of 2-month-old nulliparous or 8-month-old multiparous C3H/HeJ mice with 0.1 mg of 2-bromo-alpha-ergocryptine (CB-154) or 6-methyl-8-beta-ergoline-acetonitrile, efficacious inhibitors of prolactin secretion, markedly reduced the incidence of spontaneous mammary hyperplastic nodules and mammary tumors. CB-154 appeared to be more effective than 6-methyl-8-beta-ergoline-acetonitrile in suppressing the incidence of mammary tumors; the ergot virtually prevented the appearance of mammary tumors in nulliparous mice. Daily treatment of 5-month-old estrogen-treated, ovariectomized-hysterectomized C3H/HeJ mice for 12 months with CB-154 also significantly reduced the incidence of hyperplastic nodules and mammary tumors when compared with ovariectomized-hysterectomized mice treated with steroid alone. Daily treatment of multiparous C3H/HeJ mammary tumor-bearing mice with CB-154 or 6-methyl-8-beta-ergoline-acetonitrile generally failed, however, to promote regression of the mammary tumors. Thus significant prophylaxis of early preneoplastic lesions by drug-induced hormone (prolactin) suppression, resulting in a marked reduction in mammary tumor incidence, has been demonstrated in this study."} {"id": "PMID:1277171", "title": "Precursor lesions of bronchogenic carcinoma.", "content": "Clinical investigations and experimental studies concerned with preneoplastic and early neoplastic lesions in the respiratory tract are discussed. The occurrence of preinvasive states of carcinoma in the bronchus has been recognized for over 20 years. Histopathological and cytological studies suggest that it might become possible to identify even earlier preneoplastic precursor lesions provided the proper tissue or cell markers can be found. Experimental models that could be useful in establishing a better understanding of the evolution of the neoplastic diseases in the respiratory tract are now available.", "contents": "Precursor lesions of bronchogenic carcinoma. Clinical investigations and experimental studies concerned with preneoplastic and early neoplastic lesions in the respiratory tract are discussed. The occurrence of preinvasive states of carcinoma in the bronchus has been recognized for over 20 years. Histopathological and cytological studies suggest that it might become possible to identify even earlier preneoplastic precursor lesions provided the proper tissue or cell markers can be found. Experimental models that could be useful in establishing a better understanding of the evolution of the neoplastic diseases in the respiratory tract are now available."} {"id": "PMID:1277172", "title": "Early proliferative changes in intestinal cells.", "content": "Early lesions in the colonic mucosa of humans and rodents are characterized by similar proliferative changes within their epithelial cell population. Progressive phases of abnormal cell development appear during the evolution of neoplastic transformation in colonic cells of rodents exposed to chemical carcinogens and in humans highly susceptible to gastrointestinal cancer. Identification and classification by phenotype of cells of these individuals at increased risk for colon cancer are leading to new methods to improve the detection and diagnosis of neoplasia in high risk individuals and families. An analytical system of precise numerical definitions is aiding an approach to modify the evolution of advanced stages of neoplasia.", "contents": "Early proliferative changes in intestinal cells. Early lesions in the colonic mucosa of humans and rodents are characterized by similar proliferative changes within their epithelial cell population. Progressive phases of abnormal cell development appear during the evolution of neoplastic transformation in colonic cells of rodents exposed to chemical carcinogens and in humans highly susceptible to gastrointestinal cancer. Identification and classification by phenotype of cells of these individuals at increased risk for colon cancer are leading to new methods to improve the detection and diagnosis of neoplasia in high risk individuals and families. An analytical system of precise numerical definitions is aiding an approach to modify the evolution of advanced stages of neoplasia."} {"id": "PMID:1277173", "title": "The precursor tissue of ordinary large bowel cancer.", "content": "Hyperplastic polyps are 10 times as common as adenomas and must be distinguished from them since they are unrelated as a precursor tissue to either adenomas or carcinomas. Only adenomas are relevant to the development of the common moderately and well-differentiated large bowel cancer. Depending on three related factors (increasing size, a sessile rather than pedunculated mode of growth, and a villous rather than tubular microscopic architecture), one may find minute (1 to 2-mm) or microcancer with increasing frequency in adenomas. However, despite unlimited opportunity to do so, minute or microcancer has not been observed in normal mucosa, i.e., unassociated with adenomatous tissue. The same findings obtain in familial polyposis. In this condition, in grossly normal areas of mucosa, adenomas (but not carcinomas) as small as one or two crypts have been found. Direct one-step transformation from normal crypt cells to cancer, without formation of adenomatous epithelium, does not seem to be the usual pathway.", "contents": "The precursor tissue of ordinary large bowel cancer. Hyperplastic polyps are 10 times as common as adenomas and must be distinguished from them since they are unrelated as a precursor tissue to either adenomas or carcinomas. Only adenomas are relevant to the development of the common moderately and well-differentiated large bowel cancer. Depending on three related factors (increasing size, a sessile rather than pedunculated mode of growth, and a villous rather than tubular microscopic architecture), one may find minute (1 to 2-mm) or microcancer with increasing frequency in adenomas. However, despite unlimited opportunity to do so, minute or microcancer has not been observed in normal mucosa, i.e., unassociated with adenomatous tissue. The same findings obtain in familial polyposis. In this condition, in grossly normal areas of mucosa, adenomas (but not carcinomas) as small as one or two crypts have been found. Direct one-step transformation from normal crypt cells to cancer, without formation of adenomatous epithelium, does not seem to be the usual pathway."} {"id": "PMID:1277174", "title": "Characteristic complements of nuclear nonhistone proteins in colonic epithelial tumors.", "content": "Nuclei were isolated from colonic epithelial tumors induced in rats by the administration of 1,2-dimethylhydrazine. The nuclei were fractionated according to buoyant density by centrifugation in discontinuous sucrose density gradients. Nuclei differing in density differ in size, nonhistone protein-to-DNA ratio, and DNA synthetic activity. Their distribution in a density gradient also reflects their histological localization in the layers of the intestinal mucosa, as judged by the nuclear capacity for [3H]thymidine incorporation into DNA in vivo. Different nuclear classes isolated from the tumors contain characteristic complements of nuclear nonhistone proteins. Particularly striking accumulations of two protein classes with molecular weights of ca. 44,000 and 62,000 occur during carcinogenesis. These proteins are not uniformly distributed throughout all nuclear classes derived from the tumors. They are not at all prominent in normal colonic epithelial nuclei or in epithelial cells surroundign the tumors, or in the liver nuclei of animals treated with 1,2-dimethylhydrazine. Procedures for the differential extraction of these protein classes are described. Similar nuclear proteins have been detected in human colonic tumors and in a human cell line (HT-29) derived from an adenocarcinoma of the colon. The selective accumulation of such proteins in colonic tumor nuclei may have diagnostic value.", "contents": "Characteristic complements of nuclear nonhistone proteins in colonic epithelial tumors. Nuclei were isolated from colonic epithelial tumors induced in rats by the administration of 1,2-dimethylhydrazine. The nuclei were fractionated according to buoyant density by centrifugation in discontinuous sucrose density gradients. Nuclei differing in density differ in size, nonhistone protein-to-DNA ratio, and DNA synthetic activity. Their distribution in a density gradient also reflects their histological localization in the layers of the intestinal mucosa, as judged by the nuclear capacity for [3H]thymidine incorporation into DNA in vivo. Different nuclear classes isolated from the tumors contain characteristic complements of nuclear nonhistone proteins. Particularly striking accumulations of two protein classes with molecular weights of ca. 44,000 and 62,000 occur during carcinogenesis. These proteins are not uniformly distributed throughout all nuclear classes derived from the tumors. They are not at all prominent in normal colonic epithelial nuclei or in epithelial cells surroundign the tumors, or in the liver nuclei of animals treated with 1,2-dimethylhydrazine. Procedures for the differential extraction of these protein classes are described. Similar nuclear proteins have been detected in human colonic tumors and in a human cell line (HT-29) derived from an adenocarcinoma of the colon. The selective accumulation of such proteins in colonic tumor nuclei may have diagnostic value."} {"id": "PMID:1277175", "title": "Biochemical changes in preneoplastic rodent intestines.", "content": "Two enzymes were examined as potential indicators of early precancerous changes. Ornithine decarboxylase, an enzyme normally associated with rapid cell division, is low in the rapidly dividing, cancer-susceptible colon. The level of this enzyme was also very high in the nondividing cells of the small intestines. Administration of an intestinal carcinogen, dimethylhydrazine, led to a large increase in colonic ornithine decarboxylase but did not affect the enzyme in liver. A liver carcinogen, acetylaminofluorene, induced manyfold increases in ornithine decarboxylase of the liver but not of the colon. Studies of thymidine kinase of the gut showed that this enzyme changed quantitatively and qualitatively throughout the life of the animal, from fetal rat to newborn and adult. The tumor enzyme has many fetal-like properties. Long-term treatment with dimethylhydrazine led to changes in thymidine kinase reminiscent of the fetal enzyme. Short-term treatment caused sharp increases in the thymidine kinase of nondividing cells of the jejunum and the proximal end of the colon; similar changes in the distal end of the colon were slower in appearing and less pronounced.", "contents": "Biochemical changes in preneoplastic rodent intestines. Two enzymes were examined as potential indicators of early precancerous changes. Ornithine decarboxylase, an enzyme normally associated with rapid cell division, is low in the rapidly dividing, cancer-susceptible colon. The level of this enzyme was also very high in the nondividing cells of the small intestines. Administration of an intestinal carcinogen, dimethylhydrazine, led to a large increase in colonic ornithine decarboxylase but did not affect the enzyme in liver. A liver carcinogen, acetylaminofluorene, induced manyfold increases in ornithine decarboxylase of the liver but not of the colon. Studies of thymidine kinase of the gut showed that this enzyme changed quantitatively and qualitatively throughout the life of the animal, from fetal rat to newborn and adult. The tumor enzyme has many fetal-like properties. Long-term treatment with dimethylhydrazine led to changes in thymidine kinase reminiscent of the fetal enzyme. Short-term treatment caused sharp increases in the thymidine kinase of nondividing cells of the jejunum and the proximal end of the colon; similar changes in the distal end of the colon were slower in appearing and less pronounced."} {"id": "PMID:1277176", "title": "Morphological lesions associated with human primary invasive nonendocrine pancreas cancer.", "content": "In 227 cases of human pancreas cancer (100 pancreatectomy specimens and 127 autopsies), pancreas duct epithelium not involved by invasive cancer was examined. Pancreas duct epithelium from 100 autopsies of patients with nonpancreatic cancer, matched by age and sex to the pancreas cancer autopsy cases, was used for control studies. The prevalence of squamous metaplasia, pyloric gland metaplasia, mucous hypertrophy, and focal epithelial hyperplasia was not greatly different in the two groups. Ductal papillary hyperplasia was three times more prevalent in pancrease cancer than in controls. Marked atypia occurred in 20%, and carcinoma in situ, in 18% of the pancreas cancer cases, but neither change was seen in the control cases. It is possible that focal epithelial hyperplasia was a precursor change but that it was overgrown by the cancer. Papillary hyperplasia could not be properly evaluated as a precursor lesion because of duct obstruction, but practically all cases of marked atypia and carcinoma in situ occurred in papillary lesions. Marked atypia and carcinoma in situ, by analogy to other cancers, would appear to be precursor lesions, and their presence in association with invasive cancer lends hope to the possibility that there is a significant, recognizable, in situ phase of the disease before invasive cancer occurs.", "contents": "Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. In 227 cases of human pancreas cancer (100 pancreatectomy specimens and 127 autopsies), pancreas duct epithelium not involved by invasive cancer was examined. Pancreas duct epithelium from 100 autopsies of patients with nonpancreatic cancer, matched by age and sex to the pancreas cancer autopsy cases, was used for control studies. The prevalence of squamous metaplasia, pyloric gland metaplasia, mucous hypertrophy, and focal epithelial hyperplasia was not greatly different in the two groups. Ductal papillary hyperplasia was three times more prevalent in pancrease cancer than in controls. Marked atypia occurred in 20%, and carcinoma in situ, in 18% of the pancreas cancer cases, but neither change was seen in the control cases. It is possible that focal epithelial hyperplasia was a precursor change but that it was overgrown by the cancer. Papillary hyperplasia could not be properly evaluated as a precursor lesion because of duct obstruction, but practically all cases of marked atypia and carcinoma in situ occurred in papillary lesions. Marked atypia and carcinoma in situ, by analogy to other cancers, would appear to be precursor lesions, and their presence in association with invasive cancer lends hope to the possibility that there is a significant, recognizable, in situ phase of the disease before invasive cancer occurs."} {"id": "PMID:1277177", "title": "Approaches to prevention of epithelial cancer during the preneoplastic period.", "content": "The development of epithelial cancer is a disease process that takes many years to reach its final, invasive stage in humans. This disease process has the potential to be controlled by physiological or pharmacological means during its preneoplastic stages. Mechanisms whereby the progression of preneoplastic lesions can be stabilized, arrested, or reversed are discussed. Pharmacological enhancement of such mechanisms by synthetic vitamin A analogs (retinoids) offers a possible means for prevention of invasive epithelial cancer.", "contents": "Approaches to prevention of epithelial cancer during the preneoplastic period. The development of epithelial cancer is a disease process that takes many years to reach its final, invasive stage in humans. This disease process has the potential to be controlled by physiological or pharmacological means during its preneoplastic stages. Mechanisms whereby the progression of preneoplastic lesions can be stabilized, arrested, or reversed are discussed. Pharmacological enhancement of such mechanisms by synthetic vitamin A analogs (retinoids) offers a possible means for prevention of invasive epithelial cancer."} {"id": "PMID:1277179", "title": "Differential inhibition of embryonic cell aggregation by cultured human cells with \"malignant\" of \"normal\" characteristics.", "content": "The effect that cultured human cells have on chick embryonic neural retina cell aggregation was examined. Different types of human cultured cells inhibited aggregation of chick neural retinal cells to differetn degrees when mixed at a human cell:retina cell ration of 1:60. It appeared from the eleven cell lines studied that cells with \"malignant\" characteristics inhibited retinal cell aggregation to a greater extent than those with more \"normal\" characteristics. The assay could be used as a further test for abnormality of cell types and also as a method for studying the interactions of malignant cells with cultured cells.", "contents": "Differential inhibition of embryonic cell aggregation by cultured human cells with \"malignant\" of \"normal\" characteristics. The effect that cultured human cells have on chick embryonic neural retina cell aggregation was examined. Different types of human cultured cells inhibited aggregation of chick neural retinal cells to differetn degrees when mixed at a human cell:retina cell ration of 1:60. It appeared from the eleven cell lines studied that cells with \"malignant\" characteristics inhibited retinal cell aggregation to a greater extent than those with more \"normal\" characteristics. The assay could be used as a further test for abnormality of cell types and also as a method for studying the interactions of malignant cells with cultured cells."} {"id": "PMID:1277180", "title": "Effect of vincristine on sister chromatid exchanges of normal human lymphocytes.", "content": "In vitro analysis of the mitosis from 3-day lymphocyte cultures from two normal males and two normal females treated with bromodeoxyuridine and stained with acridine orange after addition of vincristine during different times demonstrated that vincristine inhibits the progression of the second division. When the second division progressed, the number of sister chromatid exchanges was significantly decreased. Vincristine could act by inhibiting the copying of DNA. A dosage effect is demonstrated when vincristine is added to the cultures during the first 24 hr.", "contents": "Effect of vincristine on sister chromatid exchanges of normal human lymphocytes. In vitro analysis of the mitosis from 3-day lymphocyte cultures from two normal males and two normal females treated with bromodeoxyuridine and stained with acridine orange after addition of vincristine during different times demonstrated that vincristine inhibits the progression of the second division. When the second division progressed, the number of sister chromatid exchanges was significantly decreased. Vincristine could act by inhibiting the copying of DNA. A dosage effect is demonstrated when vincristine is added to the cultures during the first 24 hr."} {"id": "PMID:1277181", "title": "The effect of Corynebacterium parvum in combination with 5-fluorouracil, L-phenylalanine mustard, or methotrexate on the inhibition of tumor growth.", "content": "Previous reports from this laboratory have demonstrated conclusively that cyclophosphamide administered asynchronously with Corynebacterium parvum (CP) results in greater C3H mammary tumor inhibition than that observed with either agent alone. An analysis of this combination has revelaed that the chemotherapeutic component contributes more significantly to tumor inhibition than does the immunotherapeutic one. This study was conducted to investigate the inhibition of C3H mammary tumors by other chemotherapeutic agents when used with CP. The results have demonstrated that 60 mg of cyclophosphamide per kg, 90 mg of 5-fluorouracil per kg, and 10 mg of L-phenylalanine mustard per kg administrated weekly have similar tumor-inhibiting properties. The addition of CP enhanced the tumor-inhibiting properties of each agent but to differing degrees. The effect of the immunopotentiator when used in combination with alkylating agents was greater than that seen when it was used with the antimetabolite 5-fluorouracil. The tumor inhibition observed when cyclophosphamide was administered asynchronously with CP was significantly greater than that observed when L-phenylalanine mustard was similarly used. Of particular interest was the finding that the addition of CP to a combination of chemotherapeutic agents resulted in no greater tumor growth inhibition than that which occurred when CP was used along with the most effective single agent in the combination. The data have indicated that, contrary to clinical impression, there is no evidence that CP through its toxicity-sparing effect permits the utilization of larger doses of chemotherapy. Consideration has been given to the mechanisms that might account for the differences in tumor growth inhibition encountered when CP was used with different chemotherapeutic agents.", "contents": "The effect of Corynebacterium parvum in combination with 5-fluorouracil, L-phenylalanine mustard, or methotrexate on the inhibition of tumor growth. Previous reports from this laboratory have demonstrated conclusively that cyclophosphamide administered asynchronously with Corynebacterium parvum (CP) results in greater C3H mammary tumor inhibition than that observed with either agent alone. An analysis of this combination has revelaed that the chemotherapeutic component contributes more significantly to tumor inhibition than does the immunotherapeutic one. This study was conducted to investigate the inhibition of C3H mammary tumors by other chemotherapeutic agents when used with CP. The results have demonstrated that 60 mg of cyclophosphamide per kg, 90 mg of 5-fluorouracil per kg, and 10 mg of L-phenylalanine mustard per kg administrated weekly have similar tumor-inhibiting properties. The addition of CP enhanced the tumor-inhibiting properties of each agent but to differing degrees. The effect of the immunopotentiator when used in combination with alkylating agents was greater than that seen when it was used with the antimetabolite 5-fluorouracil. The tumor inhibition observed when cyclophosphamide was administered asynchronously with CP was significantly greater than that observed when L-phenylalanine mustard was similarly used. Of particular interest was the finding that the addition of CP to a combination of chemotherapeutic agents resulted in no greater tumor growth inhibition than that which occurred when CP was used along with the most effective single agent in the combination. The data have indicated that, contrary to clinical impression, there is no evidence that CP through its toxicity-sparing effect permits the utilization of larger doses of chemotherapy. Consideration has been given to the mechanisms that might account for the differences in tumor growth inhibition encountered when CP was used with different chemotherapeutic agents."} {"id": "PMID:1277182", "title": "Antitumor activities of newly synthesized N4-acyl-1-beta-D-arabinofuranosylcytosine.", "content": "New derivatives of 1-beta-D-arabinofuranosylcytosine were synthesized and their antitumor activities were tested against mouse leukemia L1210. Among the 50 compounds investigated, a series of N4-acyl derivatives with long-chain saturated fatty acids were found to be highly active. The most active derivatives were N4-stearoly-1-beta-D-arabinofuranosylcytosine, which was administered in the form of suspension, and N4-behenoyl-1-beta-D-arabinofuranosylcytosine given in the form of solution. They were superior to the parent compound, 1-beta-D-arabinofuranosylcytosine, in that smaller dosages exhibited strong activities regardless of the treatment schedule, and they were also resistant to cytidine deaminase.", "contents": "Antitumor activities of newly synthesized N4-acyl-1-beta-D-arabinofuranosylcytosine. New derivatives of 1-beta-D-arabinofuranosylcytosine were synthesized and their antitumor activities were tested against mouse leukemia L1210. Among the 50 compounds investigated, a series of N4-acyl derivatives with long-chain saturated fatty acids were found to be highly active. The most active derivatives were N4-stearoly-1-beta-D-arabinofuranosylcytosine, which was administered in the form of suspension, and N4-behenoyl-1-beta-D-arabinofuranosylcytosine given in the form of solution. They were superior to the parent compound, 1-beta-D-arabinofuranosylcytosine, in that smaller dosages exhibited strong activities regardless of the treatment schedule, and they were also resistant to cytidine deaminase."} {"id": "PMID:1277183", "title": "Mammary neoplasia in a closed beagle colony.", "content": "The incidence rate of mammary neoplasia in a large colony of beagles and the relationship to internal skeletal and/or liver radiation, age, relatively late ovariectomy (4 years and older), endometritis, parity status, and adrenal weight were examined. Of these various factors, age was the only condition that was clearly correlated with changes in the mammary tumor incidence. The rate became significant at approximately eight years of age and increased progressively throughout the older age classes. Among the female dogs, the incidence of mammary cancer was higher than that of any other form of spontaneous malignancy.", "contents": "Mammary neoplasia in a closed beagle colony. The incidence rate of mammary neoplasia in a large colony of beagles and the relationship to internal skeletal and/or liver radiation, age, relatively late ovariectomy (4 years and older), endometritis, parity status, and adrenal weight were examined. Of these various factors, age was the only condition that was clearly correlated with changes in the mammary tumor incidence. The rate became significant at approximately eight years of age and increased progressively throughout the older age classes. Among the female dogs, the incidence of mammary cancer was higher than that of any other form of spontaneous malignancy."} {"id": "PMID:1277184", "title": "Flow microfluorimetric analysis of sensitive and resistant leukemia L1210 following 1-beta-D-arabinofuranosylcytosine in vivo.", "content": "Two groups of BALB/c X DBA/S F1 mice with sensitive and 1-beta-D-arabinofuranosylcytosine-resistant L1210 ascites, respectively, were used to study the cytokinetic effects of a single dose of 750 mg of 1-beta-D-arabinofuranosylcytosine per kg. Sequential DNA histograms, labeling indices, and mitotic indices were obtained from each of five mice at timed intervals from 0 to 72 hr. Each histogram was obtained by flow microfluorimetry, using the DNA-specific fluorochrome, mithramycin. The histograms were then integrated for cell cycle analysis. Cytokinetic perturbations occurred in both groups, but they were greater in the sensitive population where there was a relative accumulation of cells, mainly in early S phase, at 16 hr. This was followed by a relative depletion of S-phase cells. In the resistant population, there were relative accumulation of cells in early S phase at 8 and 24 hr and in mid-S phase at 32 hr, but there was no subsequent relative depletion of S-phase cells. The labeling index was rapidly reduced in both groups but was recovered in the resistant population within 4 hr. In the sensitive population, there was a transient rise in the labeling index at 8 and 16 hr. Sensitive and resistant populations of L1210 cells were rapidly and reliably distinguished by DNA content cell cycle analysis of a single sample taken between 24 and 72 hr following a large dose of 1-beta-D-arabinofuranosylcytosine. This technique has potential clinical application in the rational design and monitoring of chemotherapy.", "contents": "Flow microfluorimetric analysis of sensitive and resistant leukemia L1210 following 1-beta-D-arabinofuranosylcytosine in vivo. Two groups of BALB/c X DBA/S F1 mice with sensitive and 1-beta-D-arabinofuranosylcytosine-resistant L1210 ascites, respectively, were used to study the cytokinetic effects of a single dose of 750 mg of 1-beta-D-arabinofuranosylcytosine per kg. Sequential DNA histograms, labeling indices, and mitotic indices were obtained from each of five mice at timed intervals from 0 to 72 hr. Each histogram was obtained by flow microfluorimetry, using the DNA-specific fluorochrome, mithramycin. The histograms were then integrated for cell cycle analysis. Cytokinetic perturbations occurred in both groups, but they were greater in the sensitive population where there was a relative accumulation of cells, mainly in early S phase, at 16 hr. This was followed by a relative depletion of S-phase cells. In the resistant population, there were relative accumulation of cells in early S phase at 8 and 24 hr and in mid-S phase at 32 hr, but there was no subsequent relative depletion of S-phase cells. The labeling index was rapidly reduced in both groups but was recovered in the resistant population within 4 hr. In the sensitive population, there was a transient rise in the labeling index at 8 and 16 hr. Sensitive and resistant populations of L1210 cells were rapidly and reliably distinguished by DNA content cell cycle analysis of a single sample taken between 24 and 72 hr following a large dose of 1-beta-D-arabinofuranosylcytosine. This technique has potential clinical application in the rational design and monitoring of chemotherapy."} {"id": "PMID:1277185", "title": "Determination of carbocyanine dye-binding polyanions in malignant and nonmalignant disease states.", "content": "Cancer-related changes in the serum seromucoid fraction are well known. Last year Woodman published an interesting carbocyanine dye binding method for determination of serum carbohydrate polyanions in sera of normal, traumatized, and tumor-bearing mice. The usefulness of this method for clinical practice has been investigated in this study. Carbocyanine dye-binding polyanion (CPA) and the sialidase-sensitive fraction of this polyanion (SPA) have been determined in sera of 705 human subjects including healthy normal individuals and patients suffering from a broad spectrum of malignant and nonmalignant disease states. Overall, in malignant diseases the CPA and SPA values, in mg pectin equivalents per liter (mean +/-2 S.D.) (292 +/- 111 and 135 +/- 68, respectively) were significantly higher than in the serum from normal controls (166 +/- 33; 74 +/- 18) and patients hospitalized with a variety of nonmalignant disease (195 +/- 56; 92 +/- 36). The highest CPA and SPA values were found in gynecological (331 +/- 117; 149 +/- 69), bronchial (294 +/- 72; 137 +/- 51), and gastrointestinal cancers (316 +/- 111; 154 +/- 69). Elevated CPA values were found in 59.9% and elevated SPA values in 52.8% of patients suffering from malignant diseases. Successfully, radically treated cancer patients with no detectable residues or metastases for at least 1 year had values (186 +/- 39; 76 +/-24) almost within the normal ranges (93 to 250 mg pectin equivalents per liter for CPA and 35 to 120 mg pectin equivalents per liter for SPA).", "contents": "Determination of carbocyanine dye-binding polyanions in malignant and nonmalignant disease states. Cancer-related changes in the serum seromucoid fraction are well known. Last year Woodman published an interesting carbocyanine dye binding method for determination of serum carbohydrate polyanions in sera of normal, traumatized, and tumor-bearing mice. The usefulness of this method for clinical practice has been investigated in this study. Carbocyanine dye-binding polyanion (CPA) and the sialidase-sensitive fraction of this polyanion (SPA) have been determined in sera of 705 human subjects including healthy normal individuals and patients suffering from a broad spectrum of malignant and nonmalignant disease states. Overall, in malignant diseases the CPA and SPA values, in mg pectin equivalents per liter (mean +/-2 S.D.) (292 +/- 111 and 135 +/- 68, respectively) were significantly higher than in the serum from normal controls (166 +/- 33; 74 +/- 18) and patients hospitalized with a variety of nonmalignant disease (195 +/- 56; 92 +/- 36). The highest CPA and SPA values were found in gynecological (331 +/- 117; 149 +/- 69), bronchial (294 +/- 72; 137 +/- 51), and gastrointestinal cancers (316 +/- 111; 154 +/- 69). Elevated CPA values were found in 59.9% and elevated SPA values in 52.8% of patients suffering from malignant diseases. Successfully, radically treated cancer patients with no detectable residues or metastases for at least 1 year had values (186 +/- 39; 76 +/-24) almost within the normal ranges (93 to 250 mg pectin equivalents per liter for CPA and 35 to 120 mg pectin equivalents per liter for SPA)."} {"id": "PMID:1277186", "title": "Lipid hydroperoxide activation of N-hydroxy-N-acetylaminofluorene via a free radical route.", "content": "The data presented here demonstrate that linoleic acid hydroperoxide in the presence of methemoglobin or hematin activated the carcinogen N-hydroxy-N-acetyl-2-amino-fluorene via the nitroxyl free radical intermediate into 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene. Ascorbate inhibited the activation, in which case the free radical intermediate was replaced by the ascorbate free radical. On the basis of optical kinetics, we have established that the rate of linoleic acid hydroperoxide decrease paraleled the rate of N-hydroxy-N-acetyl-2-aminofluorene decrease and also the rate of 2-nitrosofluorene increase. The stoichiometry of the reaction was such that, for every 2 linoleic acid hydroperoxide molecules consumed, 2 N-hydroxy-N-acetyl-2-aminofluorene molecules were oxidized and 1 2-nitrosofluorene and 1 N-acetoxy-N-acetyl-2 aminofluorene molecule was formed.", "contents": "Lipid hydroperoxide activation of N-hydroxy-N-acetylaminofluorene via a free radical route. The data presented here demonstrate that linoleic acid hydroperoxide in the presence of methemoglobin or hematin activated the carcinogen N-hydroxy-N-acetyl-2-amino-fluorene via the nitroxyl free radical intermediate into 2-nitrosofluorene and N-acetoxy-N-acetyl-2-aminofluorene. Ascorbate inhibited the activation, in which case the free radical intermediate was replaced by the ascorbate free radical. On the basis of optical kinetics, we have established that the rate of linoleic acid hydroperoxide decrease paraleled the rate of N-hydroxy-N-acetyl-2-aminofluorene decrease and also the rate of 2-nitrosofluorene increase. The stoichiometry of the reaction was such that, for every 2 linoleic acid hydroperoxide molecules consumed, 2 N-hydroxy-N-acetyl-2-aminofluorene molecules were oxidized and 1 2-nitrosofluorene and 1 N-acetoxy-N-acetyl-2 aminofluorene molecule was formed."} {"id": "PMID:1277187", "title": "Folate deficiency in the livers of diethylnitrosaminetreated rats.", "content": "The effects of diethylnitrosamine on the metabolism of folic acid and related compounds in rat liver were investigated. The administration, in the drinking water, of diethynitrosamine to rats for 3 weeks led to decreased hepatic levels of folate, S-adenosylmethionine, and 5-methyltetrahydrofolate:homocysteine methyltransferase. Liver methylenetetrahydrofolate reductase levels were unaffected by administration of diethylnitrosamine. The polyglutamate fraction of hepatic folates obtained from rats treated with diethylnitrosamine for 3 weeks prior to injection with [3H]folate contained less radioactivity than did the polyglutamate fraction obtained from the livers of control rats treated with [3H]folate alone. Similarly, the polyglutamate folate fraction of rat livers that were simultaneously perfused with both diethylnitrosamine and [3H]folate contained less label than the polyglutamate fraction of rat livers perfused with [3H]folate only. Livers perfused with [2-14C]histidine and diethylnitrosamine produced more formiminoglutamate and less CO2 than livers treated with [2-14C]histidine only. The changes noted in the hepatic folate metabolism of diethylnitrosamine-treated rats resemble those seen in the livers of methyl-deficient rats.", "contents": "Folate deficiency in the livers of diethylnitrosaminetreated rats. The effects of diethylnitrosamine on the metabolism of folic acid and related compounds in rat liver were investigated. The administration, in the drinking water, of diethynitrosamine to rats for 3 weeks led to decreased hepatic levels of folate, S-adenosylmethionine, and 5-methyltetrahydrofolate:homocysteine methyltransferase. Liver methylenetetrahydrofolate reductase levels were unaffected by administration of diethylnitrosamine. The polyglutamate fraction of hepatic folates obtained from rats treated with diethylnitrosamine for 3 weeks prior to injection with [3H]folate contained less radioactivity than did the polyglutamate fraction obtained from the livers of control rats treated with [3H]folate alone. Similarly, the polyglutamate folate fraction of rat livers that were simultaneously perfused with both diethylnitrosamine and [3H]folate contained less label than the polyglutamate fraction of rat livers perfused with [3H]folate only. Livers perfused with [2-14C]histidine and diethylnitrosamine produced more formiminoglutamate and less CO2 than livers treated with [2-14C]histidine only. The changes noted in the hepatic folate metabolism of diethylnitrosamine-treated rats resemble those seen in the livers of methyl-deficient rats."} {"id": "PMID:1277188", "title": "The effect of phenobarbital on cyclophosphamide antitumor activity.", "content": "We have used the spleen colony assay system and survival duration studies in male DBA/2 mice with P388 leukemia to study the effects of microsomal enzyme induction by phenobarbital on the antileukemic activity and bone marrow toxicity of cyclophosphamide. Phenobarbital drinking water (0.5 mg/ml) was given for 7 days prior to cyclophosphamide (10 to 200 mg/kg i.p.). Average daily phenobarbital intake per mouse was 1.25 mg (equivalent to 4 mg/kg/day human dosage). Dose-response curves with and without phenobarbital pretreatment showed a constant 90% (1-log) reduction in the toxicity of cyclophosphamide to leukemic colony-forming units, whereas enzyme induction had no effect on the toxicity of the drug to normal bone marrow colony-forming units. Parallel survival studies confirmed the 1-log diminution in the antileukemic activity of cyclophosphamide in phenobarbital-pretreated mice. This phenobarbital-induced change in the antitumor activity of cyclophosphamide appears explainable on a pharmacokinetic basis. The Friedman and Boger assay for plasma alkylating metabolites showed that the reduction in the area under the plasma metabolite curve caused by enzyme induction exactly predicted the observed reduction in cyclophosphamide antitumor effect.", "contents": "The effect of phenobarbital on cyclophosphamide antitumor activity. We have used the spleen colony assay system and survival duration studies in male DBA/2 mice with P388 leukemia to study the effects of microsomal enzyme induction by phenobarbital on the antileukemic activity and bone marrow toxicity of cyclophosphamide. Phenobarbital drinking water (0.5 mg/ml) was given for 7 days prior to cyclophosphamide (10 to 200 mg/kg i.p.). Average daily phenobarbital intake per mouse was 1.25 mg (equivalent to 4 mg/kg/day human dosage). Dose-response curves with and without phenobarbital pretreatment showed a constant 90% (1-log) reduction in the toxicity of cyclophosphamide to leukemic colony-forming units, whereas enzyme induction had no effect on the toxicity of the drug to normal bone marrow colony-forming units. Parallel survival studies confirmed the 1-log diminution in the antileukemic activity of cyclophosphamide in phenobarbital-pretreated mice. This phenobarbital-induced change in the antitumor activity of cyclophosphamide appears explainable on a pharmacokinetic basis. The Friedman and Boger assay for plasma alkylating metabolites showed that the reduction in the area under the plasma metabolite curve caused by enzyme induction exactly predicted the observed reduction in cyclophosphamide antitumor effect."} {"id": "PMID:1277189", "title": "The effect of allopurinol on cyclophosphamide antitumor activity.", "content": "We have used the spleen colony assay system and survival duration studies in male DBA/2 mice with P388 leukemia to study the effects of allopurinol pretreatment on the antileukemic activity of cyclophosphamide and its bone marrow toxicity. Allopurinol drinking water (0.5 mg/ml) was given for 7 days prior to cyclophosphamide (10 to 200 mg/kg i.p.). Average daily allopurinol intake per mouse was 1.25 mg (equivalent to 4 mg/kg/day human dosage). Dose-response curves with and without allopurinol pretreatment showed an almost constant 0.9-log increase in the toxicity of cyclophosphamide to leukemic colony-forming units, whereas allopurinol had no effect on the toxicity of cyclophosphamide to normal bone marrow colony-forming units. Parallel survival studies revealed no difference in the antileukemic activity of cyclophosphamide as a result of allopurinol pretreatment. The allopurinol-induced change in the antitumor activity of cyclophosphamide as seen in the spleen colony assay was not explainable on the pharmacokinetic basis. Flow microfluorometric analysis of P388 leukemia tumor cell cycle parameters revealed no change in the blockading effects of cyclophosphamide as a result of allopurinol preexposure. Although we have failed to explain the underlying mechanism of this drug interaction, our data suggest that allopurinol may increase the antitumor activity of cyclophosphamide without increasing its bone marrow toxicity.", "contents": "The effect of allopurinol on cyclophosphamide antitumor activity. We have used the spleen colony assay system and survival duration studies in male DBA/2 mice with P388 leukemia to study the effects of allopurinol pretreatment on the antileukemic activity of cyclophosphamide and its bone marrow toxicity. Allopurinol drinking water (0.5 mg/ml) was given for 7 days prior to cyclophosphamide (10 to 200 mg/kg i.p.). Average daily allopurinol intake per mouse was 1.25 mg (equivalent to 4 mg/kg/day human dosage). Dose-response curves with and without allopurinol pretreatment showed an almost constant 0.9-log increase in the toxicity of cyclophosphamide to leukemic colony-forming units, whereas allopurinol had no effect on the toxicity of cyclophosphamide to normal bone marrow colony-forming units. Parallel survival studies revealed no difference in the antileukemic activity of cyclophosphamide as a result of allopurinol pretreatment. The allopurinol-induced change in the antitumor activity of cyclophosphamide as seen in the spleen colony assay was not explainable on the pharmacokinetic basis. Flow microfluorometric analysis of P388 leukemia tumor cell cycle parameters revealed no change in the blockading effects of cyclophosphamide as a result of allopurinol preexposure. Although we have failed to explain the underlying mechanism of this drug interaction, our data suggest that allopurinol may increase the antitumor activity of cyclophosphamide without increasing its bone marrow toxicity."} {"id": "PMID:1277190", "title": "Histological comparison of the growth of rat bladder carcinoma R-4909 observed for two years in vitro and in vivo.", "content": "A transplantable bladder tumor (Chapman R-4909) of the rat, when first received in our laboratory, grew with a complex histopathology. The predominant component was transitional cell carcinoma, but there were foci of keratinization, including pearl formation, and foci of a less well-defined cystic appearance. We report here observations made during the first 2 years of an ongoing study on the divergent histopathology of R-4909 under several conditions of propagation. During the entire period, the tumor has been maintained by serial passage in rats (Fischer 344) and by serial passage in vitro. At intervals, cells of the tissue culture series were inoculated into rats to compare the histopathology of animal- and culture-passed strains. We obtained several clones from the stock cultures and these also were maintained continuously in vitro. At intervals, cells from two of these lineages, clone A and clone B, were inoculated into rats. After 2 years, cells maintained in stock culture, on injection into new rats, produced growths similar to the original in that all three epithelial patterns, transitional, squamous, and adenomatous, were perpetuated. In contrast, the tumor passed exclusively in vivo lost its squamous component completely. It became anaplastic, with tissue architecture almost entirely adenomatous and cystic. Unlike the stock tissue culture line, the clonal isolates following prolonged culture produced adenomatous tumors only. In a related preliminary study, we inoculated into rats R-4909 cells that had been cultivated for up to 2 months under aerobic and anaerobic conditions. Tumors grew in most of the animals, and those of the aerobic group were more cystic than the others.", "contents": "Histological comparison of the growth of rat bladder carcinoma R-4909 observed for two years in vitro and in vivo. A transplantable bladder tumor (Chapman R-4909) of the rat, when first received in our laboratory, grew with a complex histopathology. The predominant component was transitional cell carcinoma, but there were foci of keratinization, including pearl formation, and foci of a less well-defined cystic appearance. We report here observations made during the first 2 years of an ongoing study on the divergent histopathology of R-4909 under several conditions of propagation. During the entire period, the tumor has been maintained by serial passage in rats (Fischer 344) and by serial passage in vitro. At intervals, cells of the tissue culture series were inoculated into rats to compare the histopathology of animal- and culture-passed strains. We obtained several clones from the stock cultures and these also were maintained continuously in vitro. At intervals, cells from two of these lineages, clone A and clone B, were inoculated into rats. After 2 years, cells maintained in stock culture, on injection into new rats, produced growths similar to the original in that all three epithelial patterns, transitional, squamous, and adenomatous, were perpetuated. In contrast, the tumor passed exclusively in vivo lost its squamous component completely. It became anaplastic, with tissue architecture almost entirely adenomatous and cystic. Unlike the stock tissue culture line, the clonal isolates following prolonged culture produced adenomatous tumors only. In a related preliminary study, we inoculated into rats R-4909 cells that had been cultivated for up to 2 months under aerobic and anaerobic conditions. Tumors grew in most of the animals, and those of the aerobic group were more cystic than the others."} {"id": "PMID:1277191", "title": "Prolonged tumor dormancy by prevention of neovascularization in the vitreous.", "content": "Tumors release a diffusible substance that stimulates neovascularization. To study the neovascularization that occurs in diabetic retinopathy, we implanted V2 carcinomas and mouse ependymoblastomas into the vitreous of experimental animals. In the vitreous, unlike previous sites, the tumors failed to stimulate neovascularization. They grew for weeks as small, unvascularized, three-dimensional aggregates of cells. Explosive growth into a large, vascularized mass occurred when the avascular tumors reached the retinal surface. The vitreous proved to be a valuable model for observing the in vivo growth of small, solid tumors. Xenografts survived for months without evidence of immune rejection. The consequence of the prolonged avascular state is the restriction of tumor size. The normal vitreous may act to inhibit capillary proliferation. An understanding of the mechanism for maintaining the avascular state may lead to therapeutic blockade of neovascularization. This would be important in the management of diabetic retinopathy and neoplasia.", "contents": "Prolonged tumor dormancy by prevention of neovascularization in the vitreous. Tumors release a diffusible substance that stimulates neovascularization. To study the neovascularization that occurs in diabetic retinopathy, we implanted V2 carcinomas and mouse ependymoblastomas into the vitreous of experimental animals. In the vitreous, unlike previous sites, the tumors failed to stimulate neovascularization. They grew for weeks as small, unvascularized, three-dimensional aggregates of cells. Explosive growth into a large, vascularized mass occurred when the avascular tumors reached the retinal surface. The vitreous proved to be a valuable model for observing the in vivo growth of small, solid tumors. Xenografts survived for months without evidence of immune rejection. The consequence of the prolonged avascular state is the restriction of tumor size. The normal vitreous may act to inhibit capillary proliferation. An understanding of the mechanism for maintaining the avascular state may lead to therapeutic blockade of neovascularization. This would be important in the management of diabetic retinopathy and neoplasia."} {"id": "PMID:1277192", "title": "The sensitivities of human and murine hemopoietic cells exposed to cytotoxic drugs in an in vivo culture system.", "content": "An agar diffusion chamber technique has been used to measure the sensitivities of human and murine hemopoietic colony-forming cells to cytotoxic drugs. The cells were held in i.p. diffusion chambers and exposed to the cytotoxic drugs by i.v. injection of the host mice. This method allows some account to be taken of the continuous changes in activity during the metabolic degradation of the drug. To determine how far this system provides a valid measure of the sensitivity of the cells in hemopoietic tissue, the responses of mouse bone marrow exposed to the drugs in situ in the donor mouse were compared with those of mouse cells exposed in diffusion chambers. The dose-response curves for cyclophosphamide and 5-fluorouracil were exponential in all cases. Exponential survival curves were also seen when human and mouse colony-forming cells were exposed to vinblastine or methotrexate in diffusion chambers. The plateaus seen when mouse cells were exposed to these drugs in situ could, however, be regained by omitting agar from the chambers during the exposure period. The results indicate that there are differences between the sensitivities of human and mouse marrow cells to cytotoxic drugs and that any extrapolation from mouse to humans must be viewed with caution.", "contents": "The sensitivities of human and murine hemopoietic cells exposed to cytotoxic drugs in an in vivo culture system. An agar diffusion chamber technique has been used to measure the sensitivities of human and murine hemopoietic colony-forming cells to cytotoxic drugs. The cells were held in i.p. diffusion chambers and exposed to the cytotoxic drugs by i.v. injection of the host mice. This method allows some account to be taken of the continuous changes in activity during the metabolic degradation of the drug. To determine how far this system provides a valid measure of the sensitivity of the cells in hemopoietic tissue, the responses of mouse bone marrow exposed to the drugs in situ in the donor mouse were compared with those of mouse cells exposed in diffusion chambers. The dose-response curves for cyclophosphamide and 5-fluorouracil were exponential in all cases. Exponential survival curves were also seen when human and mouse colony-forming cells were exposed to vinblastine or methotrexate in diffusion chambers. The plateaus seen when mouse cells were exposed to these drugs in situ could, however, be regained by omitting agar from the chambers during the exposure period. The results indicate that there are differences between the sensitivities of human and mouse marrow cells to cytotoxic drugs and that any extrapolation from mouse to humans must be viewed with caution."} {"id": "PMID:1277193", "title": "Spontaneous extracellular synthesis of DNA released by human blood lymphocytes.", "content": "Human lymphocytes were shown to release, in vitro and in the absence of any stimulation, a complex containing DNA. It has also been reported that the release process is unrelated to cell death and is regulated by a homeostatic mechanism. Some properties of the extracellular DNA were investigated. When a phosphorylated precursor was added to the cell-free supernatant, the DNA recovered from the medium was labeled. Evidence that DNA lebeling represented true precursor incorporation and not simple attachment was obtained from nearest neighbor analysis data. When [alpha-32P]thymidine triphosphate was added to the supernatant and the labeled DNA was completely hydrolyzed to 3'-deoxyribonucleotides, radioactivity was found in all four nucleotides. Although the exact kind of synthesis cannot be determined at this stage, the possibility of a terminal transferase system in which the enzyme would merely add a nucleotide at the end of the chain was eliminated since comparative digestion with DNase and venom phosphodiesterase showed that labeling was located along the whole length of the chain. Precursor incorporation into the DNA was inhibited by DNase, RNase, Pronase, and actinomycin D. This extracellular synthesis was not affected by cell death rate. The renaturation curve of the extracellular [3H]DNA synthesized in the cell-free medium showed a lack of gene reiteration suggesting a preferential synthesis of unique sequences.", "contents": "Spontaneous extracellular synthesis of DNA released by human blood lymphocytes. Human lymphocytes were shown to release, in vitro and in the absence of any stimulation, a complex containing DNA. It has also been reported that the release process is unrelated to cell death and is regulated by a homeostatic mechanism. Some properties of the extracellular DNA were investigated. When a phosphorylated precursor was added to the cell-free supernatant, the DNA recovered from the medium was labeled. Evidence that DNA lebeling represented true precursor incorporation and not simple attachment was obtained from nearest neighbor analysis data. When [alpha-32P]thymidine triphosphate was added to the supernatant and the labeled DNA was completely hydrolyzed to 3'-deoxyribonucleotides, radioactivity was found in all four nucleotides. Although the exact kind of synthesis cannot be determined at this stage, the possibility of a terminal transferase system in which the enzyme would merely add a nucleotide at the end of the chain was eliminated since comparative digestion with DNase and venom phosphodiesterase showed that labeling was located along the whole length of the chain. Precursor incorporation into the DNA was inhibited by DNase, RNase, Pronase, and actinomycin D. This extracellular synthesis was not affected by cell death rate. The renaturation curve of the extracellular [3H]DNA synthesized in the cell-free medium showed a lack of gene reiteration suggesting a preferential synthesis of unique sequences."} {"id": "PMID:1277194", "title": "A galactosidase immunosorbent test for carcinoembryonic antigen.", "content": "A galactosidase immunosorbent test for carcinoembryonic antigen (CEA) is described in which the amount of galactosidase adsorbed to a cellulose disc is a hyperbolic function of CEA concentration. Thus, molecules with CEA-like activity can be characterized by mathematical analysis of data obtained from the galactosidase immunosorbent test. By such analysis, CEA-reactive molecules in normal human plasma were distinguished from normal cross-reacting antigen and from authentic CEA. Variation of the amount of antibody-enzyme conjugate used in the galactosidase immunosorbent test permitted CEA-reactive material in plasma of a patient with rectal carcinoma to be antigenically distinguished from the CEA-reactive material in urine of a patient with bladder carcinoma. The galactosidase immunosorbent test is a useful tool for analysis of CEA-reactive molecules.", "contents": "A galactosidase immunosorbent test for carcinoembryonic antigen. A galactosidase immunosorbent test for carcinoembryonic antigen (CEA) is described in which the amount of galactosidase adsorbed to a cellulose disc is a hyperbolic function of CEA concentration. Thus, molecules with CEA-like activity can be characterized by mathematical analysis of data obtained from the galactosidase immunosorbent test. By such analysis, CEA-reactive molecules in normal human plasma were distinguished from normal cross-reacting antigen and from authentic CEA. Variation of the amount of antibody-enzyme conjugate used in the galactosidase immunosorbent test permitted CEA-reactive material in plasma of a patient with rectal carcinoma to be antigenically distinguished from the CEA-reactive material in urine of a patient with bladder carcinoma. The galactosidase immunosorbent test is a useful tool for analysis of CEA-reactive molecules."} {"id": "PMID:1277195", "title": "Application of a galactosidase immunosorbent test to carcinoembryonic antigen in plasma.", "content": "The galactosidase immunosorbent test for carcinoembryonic antigen is simple to perform, uses stable reagents, does not require radioactive reagents, and is adaptable to large numbers of samples. Concentration of carcinoembryonic antigen in sera or plasma was determined by the galactosidase immunosorbent test and by the Egan-Todd double antibody assay (93% agreement), indirect Z-gel (83% agreement), and direct Z-gel assay (ps = 0.97). The galactosidase immunosorbent test has potential as a clinically useful nonisotopic assay for carcinoembryonic antigen.", "contents": "Application of a galactosidase immunosorbent test to carcinoembryonic antigen in plasma. The galactosidase immunosorbent test for carcinoembryonic antigen is simple to perform, uses stable reagents, does not require radioactive reagents, and is adaptable to large numbers of samples. Concentration of carcinoembryonic antigen in sera or plasma was determined by the galactosidase immunosorbent test and by the Egan-Todd double antibody assay (93% agreement), indirect Z-gel (83% agreement), and direct Z-gel assay (ps = 0.97). The galactosidase immunosorbent test has potential as a clinically useful nonisotopic assay for carcinoembryonic antigen."} {"id": "PMID:1277196", "title": "In vitro correlates of transformation in C3H/10T1/2 clone 8 mouse cells.", "content": "Various potential in vitro correlates of malignancy were studied in four chemically transformed C3H/10T1/2 Clone 8 mouse cell lines and were compared with controls cells. The degree of tumorigenicity was best predicted by the relative plating efficiencies of the morphologically transformed cells in soft agar. All transformed cells also showed an increase in extracellular fibrinolytic activity which may be an additional marker for transformation. Intracellular fibrinolytic activity and loss of 125I-labeled cell surface protein (M.W. 250,000) were not correlated with morphological transformation or tumorigenicity in these cells.", "contents": "In vitro correlates of transformation in C3H/10T1/2 clone 8 mouse cells. Various potential in vitro correlates of malignancy were studied in four chemically transformed C3H/10T1/2 Clone 8 mouse cell lines and were compared with controls cells. The degree of tumorigenicity was best predicted by the relative plating efficiencies of the morphologically transformed cells in soft agar. All transformed cells also showed an increase in extracellular fibrinolytic activity which may be an additional marker for transformation. Intracellular fibrinolytic activity and loss of 125I-labeled cell surface protein (M.W. 250,000) were not correlated with morphological transformation or tumorigenicity in these cells."} {"id": "PMID:1277197", "title": "Colon carcinogenesis in germ-free rats with intrarectal 1,2-dimethylhydrazine and subcutaneous azoxymethane.", "content": "The effect of intestinal microflora on colon carcinogenesis by 1,2-dimethylhydrazine and azoxymethane was studied, with the use of germ-free and conventional female Fischer rats. At 7 weeks of age, germ-free and conventional rats were treated with 20 weekly intrarectal 1,2-dimethylhydrazine (20 mg per kg body weight per week) or subcutaneous azoxymethane (10 mg per kg body weight per week) doses and were autopsied 15 weeks later. Tumors were induced in the small intestine and colon of germ-free and conventional rats treated with intrarectal 1,2-dimethylhydrazine; the number of rats with colon tumors and the multiplicity of tumors were decreased in germ-free rats, compared with conventional animals. Azoxymethane given subcutaneously increased the incidence and multiplicity of colon tumors in germ-free rats, compared with conventional controls. It is concluded that the intestinal microflora alter the carcinogenic and/or cocarcinogenic effect of different compounds in the large intestine.", "contents": "Colon carcinogenesis in germ-free rats with intrarectal 1,2-dimethylhydrazine and subcutaneous azoxymethane. The effect of intestinal microflora on colon carcinogenesis by 1,2-dimethylhydrazine and azoxymethane was studied, with the use of germ-free and conventional female Fischer rats. At 7 weeks of age, germ-free and conventional rats were treated with 20 weekly intrarectal 1,2-dimethylhydrazine (20 mg per kg body weight per week) or subcutaneous azoxymethane (10 mg per kg body weight per week) doses and were autopsied 15 weeks later. Tumors were induced in the small intestine and colon of germ-free and conventional rats treated with intrarectal 1,2-dimethylhydrazine; the number of rats with colon tumors and the multiplicity of tumors were decreased in germ-free rats, compared with conventional animals. Azoxymethane given subcutaneously increased the incidence and multiplicity of colon tumors in germ-free rats, compared with conventional controls. It is concluded that the intestinal microflora alter the carcinogenic and/or cocarcinogenic effect of different compounds in the large intestine."} {"id": "PMID:1277198", "title": "N-nitroso-bis(2-acetoxypropyl)amine as a further pancreatic carcinogen in Syrian golden hamsters.", "content": "N-Nitroso-bis(2-acetoxypropyl)amine, a possible beta metabolite of N-nitroso-di-n-propylamine, was shown to be a potent carcinogen in the Syrian golden hamster. After a single s.c. treatment, the pancreas was the most affected organ, followed by the liver, respiratory tract, and kidneys. However, repeated application resulted in a higher incidence of neoplasms of the respiratory tract than of the pancreas and kidneys. The effect of N-nitroso-bis(2-acetoxypropyl)amine on toxicity, target tissues, and carcinogenicity was similar to that of N-nitroso-bis(2-hydroxypropyl)amine. The assumption that these two compounds may have similar metabolic pathways was confirmed; N-nitroso-bis(2-acetoxypropyl)amine was readily deesterified to N-nitroso-bis(2-hydroxypropyl)amine in vivo and in vitro.", "contents": "N-nitroso-bis(2-acetoxypropyl)amine as a further pancreatic carcinogen in Syrian golden hamsters. N-Nitroso-bis(2-acetoxypropyl)amine, a possible beta metabolite of N-nitroso-di-n-propylamine, was shown to be a potent carcinogen in the Syrian golden hamster. After a single s.c. treatment, the pancreas was the most affected organ, followed by the liver, respiratory tract, and kidneys. However, repeated application resulted in a higher incidence of neoplasms of the respiratory tract than of the pancreas and kidneys. The effect of N-nitroso-bis(2-acetoxypropyl)amine on toxicity, target tissues, and carcinogenicity was similar to that of N-nitroso-bis(2-hydroxypropyl)amine. The assumption that these two compounds may have similar metabolic pathways was confirmed; N-nitroso-bis(2-acetoxypropyl)amine was readily deesterified to N-nitroso-bis(2-hydroxypropyl)amine in vivo and in vitro."} {"id": "PMID:1277199", "title": "Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells.", "content": "The effect of adriamycin on DNA, RNA, and protein synthesis was investigated in cell-free systems and intact cells. In studies with purified mammalian cell enzymes, adriamycin produced a greater inhibition of DNA-dependent DNA polymerase than of RNA polymerase. The extent of inhibition of both these enzymes was decreased by increasing the concentration of the DNA template in the reaction mixture. In studies with isolated nuclei, adriamycin was also a more potent inhibitor of DNA synthesis than RNA synthesis. However, with intact cells, adriamycin inhibited both DNA and RNA synthesis to about the same extent. The inhibition produced by adriamycin on RNA synthesis in intact cells was greater than that observed in the cell-free systems. Adriamycin inhibited protein synthesis in a cell-free system consisting of polyribosomes, transfer RNA, and enzymes but did not inhibit protein synthesis in intact cells. These differences in the pattern of inhibition may be due to biotransformation of the drug and/or preferential binding to chromosomal DNA in the intact cell.", "contents": "Effect of adriamycin on DNA, RNA, and protein synthesis in cell-free systems and intact cells. The effect of adriamycin on DNA, RNA, and protein synthesis was investigated in cell-free systems and intact cells. In studies with purified mammalian cell enzymes, adriamycin produced a greater inhibition of DNA-dependent DNA polymerase than of RNA polymerase. The extent of inhibition of both these enzymes was decreased by increasing the concentration of the DNA template in the reaction mixture. In studies with isolated nuclei, adriamycin was also a more potent inhibitor of DNA synthesis than RNA synthesis. However, with intact cells, adriamycin inhibited both DNA and RNA synthesis to about the same extent. The inhibition produced by adriamycin on RNA synthesis in intact cells was greater than that observed in the cell-free systems. Adriamycin inhibited protein synthesis in a cell-free system consisting of polyribosomes, transfer RNA, and enzymes but did not inhibit protein synthesis in intact cells. These differences in the pattern of inhibition may be due to biotransformation of the drug and/or preferential binding to chromosomal DNA in the intact cell."} {"id": "PMID:1277200", "title": "Separation and characterization of transcriptionally active and inactive nuclear subfractions of AKR mouse embryo cells.", "content": "This study was initiated with the objective of separating and characterizing two or more nuclear subfractions, which could then be compared with respect to their relative propensity for binding carcinogenic polycyclic aromatic hydrocarbons. Nuclei were isolated from cloned AKR-2B mouse embryo cells, which are susceptible to transformation by chemical carcinogens. The nuclei were mechanically sheared and subfractions were separated by sedimentation through a 0.17 to 1.7 M sucrose gradient. When the cells were treated with [3H]uridine for 30 min, most of the label incorporated into RNA was recovered in the top region of the gradients, which represented Nuclear Subfraction I. The majority of the chromatin DNA, however was localized in the bottom region (Subfraction II) and the pellet (Subfraction III). Precipitation (with CaCl2) of the rapidly labeled RNA of Subfraction I along with the chromatin DNA suggested that the label was present in nascent RNA chains still attached to the chromatin. Thus, the transcripitionally active chromatin seemed to be localized in Nuclear Subfraction I. The chromatin of Subfraction I was also the best template for RNA synthesis in vitro with exogenous bacterial polymerase. The protein and RNA content of subfraction I was greater than that of the other two subfractions and whole chromatin. Electron microscopy revealed the presence of membrane material in Subfraction I and II, with little such material in Subfraction III. Subfraction I differed from Subfractions II and II and whole chromation with respect to thermal denaturation of the DNA and histone composition (as determined by gel electrophoresis). The acidic protein composition (as determined by gel electrophoresis) differed for the chromatin of all three nuclear subfractions.", "contents": "Separation and characterization of transcriptionally active and inactive nuclear subfractions of AKR mouse embryo cells. This study was initiated with the objective of separating and characterizing two or more nuclear subfractions, which could then be compared with respect to their relative propensity for binding carcinogenic polycyclic aromatic hydrocarbons. Nuclei were isolated from cloned AKR-2B mouse embryo cells, which are susceptible to transformation by chemical carcinogens. The nuclei were mechanically sheared and subfractions were separated by sedimentation through a 0.17 to 1.7 M sucrose gradient. When the cells were treated with [3H]uridine for 30 min, most of the label incorporated into RNA was recovered in the top region of the gradients, which represented Nuclear Subfraction I. The majority of the chromatin DNA, however was localized in the bottom region (Subfraction II) and the pellet (Subfraction III). Precipitation (with CaCl2) of the rapidly labeled RNA of Subfraction I along with the chromatin DNA suggested that the label was present in nascent RNA chains still attached to the chromatin. Thus, the transcripitionally active chromatin seemed to be localized in Nuclear Subfraction I. The chromatin of Subfraction I was also the best template for RNA synthesis in vitro with exogenous bacterial polymerase. The protein and RNA content of subfraction I was greater than that of the other two subfractions and whole chromatin. Electron microscopy revealed the presence of membrane material in Subfraction I and II, with little such material in Subfraction III. Subfraction I differed from Subfractions II and II and whole chromation with respect to thermal denaturation of the DNA and histone composition (as determined by gel electrophoresis). The acidic protein composition (as determined by gel electrophoresis) differed for the chromatin of all three nuclear subfractions."} {"id": "PMID:1277201", "title": "Binding of polycyclic aromatic hydrocarbons to transcriptionally active nuclear subfractions of AKR mouse embryo cells.", "content": "The objective of this study was to examine the binding of carcinogenic polycyclic aromatic hydrocarbons in well-characterized nuclear subfractions from transformable cells in culture. A cloned line of AKR mouse embryo cells was exposed to culture medium containing [3H]-3-methyl-cholanthrene (MC) (0.4 mug/ml) 670 Ci/mole). Cellular uptake and nuclear binding were determined after 4 hr of exposure. The addition of unlabeled MC up to 10 mug/ml did not cause reduction of [3H]MC cellular uptake or nuclear binding. From 2 to 5% of the total cellular MC was localized in the nuclei. All nuclear subfractions obtained from mechanically sheared nuclei and separated on sucrose gradients showed some MC binding; however, a high-affinity, high-specific-activity binding of MC was associated only with the slower-sedimenting component shown to represent that fraction of nuclear chromatin that is transcriptionally active. Conditions that caused the precipitation of this chromatin also resulted in the precipitation of the radioactive compound, thus suggesting that the MC was physically bound to the chromatin. Unlabeled MC (10 mug/ml) saturated this high-affinity MC binding to the transcripitionally active chromatin but did not saturate the binding to the other nuclear fractions. The binding of another potent carcinogen, [3H]-1,2,5,6-dibenzanthracene, and the \"weak\" carcinogen, [3H]-1,2,3,4-dibenzanthracene (3,4-DBA), to whole nuclei and nuclear subfractions was also determined. The concentration, specific activity, and time of treatment were identical with those used for MC. The level of binding of [3H]-1,2,5,6-dibenzanthracene was approximately 3-fold greater in whole nuclei on a per mass DNA basis than in those of either the MC or the 3,4-DBA. The binding of MC and 3,4-DBA to whole nuclei was approximately equal. As with MC, the [3H]-1,2,5,6-dibenzanthracene demonstrated a peak of high specific activity binding to the slower-sedimenting fraction of chromatin while the 3,4-DBA displayed considerably less binding to this fraction.", "contents": "Binding of polycyclic aromatic hydrocarbons to transcriptionally active nuclear subfractions of AKR mouse embryo cells. The objective of this study was to examine the binding of carcinogenic polycyclic aromatic hydrocarbons in well-characterized nuclear subfractions from transformable cells in culture. A cloned line of AKR mouse embryo cells was exposed to culture medium containing [3H]-3-methyl-cholanthrene (MC) (0.4 mug/ml) 670 Ci/mole). Cellular uptake and nuclear binding were determined after 4 hr of exposure. The addition of unlabeled MC up to 10 mug/ml did not cause reduction of [3H]MC cellular uptake or nuclear binding. From 2 to 5% of the total cellular MC was localized in the nuclei. All nuclear subfractions obtained from mechanically sheared nuclei and separated on sucrose gradients showed some MC binding; however, a high-affinity, high-specific-activity binding of MC was associated only with the slower-sedimenting component shown to represent that fraction of nuclear chromatin that is transcriptionally active. Conditions that caused the precipitation of this chromatin also resulted in the precipitation of the radioactive compound, thus suggesting that the MC was physically bound to the chromatin. Unlabeled MC (10 mug/ml) saturated this high-affinity MC binding to the transcripitionally active chromatin but did not saturate the binding to the other nuclear fractions. The binding of another potent carcinogen, [3H]-1,2,5,6-dibenzanthracene, and the \"weak\" carcinogen, [3H]-1,2,3,4-dibenzanthracene (3,4-DBA), to whole nuclei and nuclear subfractions was also determined. The concentration, specific activity, and time of treatment were identical with those used for MC. The level of binding of [3H]-1,2,5,6-dibenzanthracene was approximately 3-fold greater in whole nuclei on a per mass DNA basis than in those of either the MC or the 3,4-DBA. The binding of MC and 3,4-DBA to whole nuclei was approximately equal. As with MC, the [3H]-1,2,5,6-dibenzanthracene demonstrated a peak of high specific activity binding to the slower-sedimenting fraction of chromatin while the 3,4-DBA displayed considerably less binding to this fraction."} {"id": "PMID:1277202", "title": "Antitumor and immunosuppressive effects of mycophenolic acid derivatives.", "content": "Thirth-three derivatives of mycophenolic acid obtained by modifying phenolic hydroxyl and/or carboxyl groups were examined for antitumor and immunosuppressive activities. Some compounds showed more potent antitumor activities to L1210 leukemia and Ehrlich solid tumor than did mycophenolic acid. Most of these suppressed the production of antibody against sheep red blood cells in mice as strongly as did the parent substance. Correlation between antitumor and immunosuppressive activities was generally observed. However, a few compounds possessed a potent antitumor activity with less or no immunosuppressive activity.", "contents": "Antitumor and immunosuppressive effects of mycophenolic acid derivatives. Thirth-three derivatives of mycophenolic acid obtained by modifying phenolic hydroxyl and/or carboxyl groups were examined for antitumor and immunosuppressive activities. Some compounds showed more potent antitumor activities to L1210 leukemia and Ehrlich solid tumor than did mycophenolic acid. Most of these suppressed the production of antibody against sheep red blood cells in mice as strongly as did the parent substance. Correlation between antitumor and immunosuppressive activities was generally observed. However, a few compounds possessed a potent antitumor activity with less or no immunosuppressive activity."} {"id": "PMID:1277203", "title": "Reduction of ifosfamide toxicity using dose fractionation.", "content": "Ifosfamide was given in i.v. doses of 600 to 1200 mg/sq m/day for 5 days to 32 cancer patients, refractory to prior therapy, in an attempt to investigate the possibility of reducing toxicity by dose fractionation. Microscopic hematuria occurred in 14% and gross hematuria in only 10% of the patient trials. Azotemia did not occur in any patient on this study. Reversible myelosuppression was comparable to that found by other investigators. Other side effects such as nausea and mental confusion occurred infrequently. Ifosfamide produced antitumor effect in 7 of 27 evaluable patients. This study indicates that the renal and bladder toxicity of ifosfamide can be substantially reduced if the drug is administered in i.v. infusions of 1 to 2 hr daily for 5 days.", "contents": "Reduction of ifosfamide toxicity using dose fractionation. Ifosfamide was given in i.v. doses of 600 to 1200 mg/sq m/day for 5 days to 32 cancer patients, refractory to prior therapy, in an attempt to investigate the possibility of reducing toxicity by dose fractionation. Microscopic hematuria occurred in 14% and gross hematuria in only 10% of the patient trials. Azotemia did not occur in any patient on this study. Reversible myelosuppression was comparable to that found by other investigators. Other side effects such as nausea and mental confusion occurred infrequently. Ifosfamide produced antitumor effect in 7 of 27 evaluable patients. This study indicates that the renal and bladder toxicity of ifosfamide can be substantially reduced if the drug is administered in i.v. infusions of 1 to 2 hr daily for 5 days."} {"id": "PMID:1277204", "title": "Delayed and progressive myocardial lesions after adriamycin administration in the rabbit.", "content": "A cardiomyopathy similar to that observed in cancer patients after prolonged chemotherapy with adriamycin can be produced in the rabbit, characterized by mitochondrial and myofilamentous degeneration with noninflammatory myolysis and connective tissue repair. The progressive and delayed myocardial lesions produced in rabbits receiving increasing total doses of adriamycin were studied after 23, 35, 43, and 77 days of continuous treatment and in posttreatment periods up to 150 to 180 days after the last administration of adriamycin. Total adriamycin doses that produced increased serum enzyme, myocardial sodium, and calcium levels but that failed to elicit serious myocardial morphological lesions during the period of drug administration resulted in a delayed cardiomyopathy leaving focal areas of fibrosis and progressive lesions that became more severe after discontinuation of drug administration. These findings suggest that the myocardial effects of adriamycin are cumulative and potentially nonreversible.", "contents": "Delayed and progressive myocardial lesions after adriamycin administration in the rabbit. A cardiomyopathy similar to that observed in cancer patients after prolonged chemotherapy with adriamycin can be produced in the rabbit, characterized by mitochondrial and myofilamentous degeneration with noninflammatory myolysis and connective tissue repair. The progressive and delayed myocardial lesions produced in rabbits receiving increasing total doses of adriamycin were studied after 23, 35, 43, and 77 days of continuous treatment and in posttreatment periods up to 150 to 180 days after the last administration of adriamycin. Total adriamycin doses that produced increased serum enzyme, myocardial sodium, and calcium levels but that failed to elicit serious myocardial morphological lesions during the period of drug administration resulted in a delayed cardiomyopathy leaving focal areas of fibrosis and progressive lesions that became more severe after discontinuation of drug administration. These findings suggest that the myocardial effects of adriamycin are cumulative and potentially nonreversible."} {"id": "PMID:1277205", "title": "Comparative pharmacologic study in vitro and in vivo with cyclophosphamide (NSC-26271), cyclophosphamide metabolites, and plain nitrogen mustard compounds.", "content": "This paper deals with the problem of the relative selectivity of the antitumor effect of cyclophosphamide (CP). CP and its metabolites are pharmacologically characterized by determining their chemical and biological activities in vitro and their pharmacotherapeutic properties in vivo. Of particular importance is the specificity of the cytotoxic activity (cytostatic units/mumol) in vitro and the margin of safety (therapeutic index) in vivo. The pharmacologic data reveal: a. Of the various metabolites of CP only 4-hydroxycyclophosphamide, the primary activation product, exerts a highly specific cytotoxic activity in vitro and has a wide margin of safety in vivo. b. The decisive step in toxication is the formation of the alkylating N,N-bis(2-chloroethyl)phosphorodiamidic acid after acrolein has been split off.", "contents": "Comparative pharmacologic study in vitro and in vivo with cyclophosphamide (NSC-26271), cyclophosphamide metabolites, and plain nitrogen mustard compounds. This paper deals with the problem of the relative selectivity of the antitumor effect of cyclophosphamide (CP). CP and its metabolites are pharmacologically characterized by determining their chemical and biological activities in vitro and their pharmacotherapeutic properties in vivo. Of particular importance is the specificity of the cytotoxic activity (cytostatic units/mumol) in vitro and the margin of safety (therapeutic index) in vivo. The pharmacologic data reveal: a. Of the various metabolites of CP only 4-hydroxycyclophosphamide, the primary activation product, exerts a highly specific cytotoxic activity in vitro and has a wide margin of safety in vivo. b. The decisive step in toxication is the formation of the alkylating N,N-bis(2-chloroethyl)phosphorodiamidic acid after acrolein has been split off."} {"id": "PMID:1277206", "title": "The problem of oncostatic specificity of cyclophosphamide (NSC-26271): Studies on reactions that control the alkylating and cytotoxic activity.", "content": "The relatively high oncostatic specificity of cyclophosphamide (CP) in vivo is shown to be due to the cytotoxic specificity of 4-hydroxycyclophosphamide (4-hydroxy-CP), the first product of metabolic activation of CP in the liver. This specificity can be evaluated not only in vivo by measuring the therapeutic index, but also in vitro by determining its cytotoxicity against Yoshida ascites tumor cells. Evidence is given that 4-hydroxy-CP is not an alkylating agent itself, but attains this property only by release of an alkylating N,N-(2-chloroethyl)phosphorodiamic acid moiety and acrolein. The energetic source for this rate-limiting toxication results from the resonance stabilization of the released acrolein. Reactions at the cryptoaldehyde group of 4-hydroxy-CP, which reduce or prevent the resonance stabilization of the 3-carbon unit to be released, lead to a deactivation of the primary metabolite of CP thus reducing or even preventing toxication, and hence influencing both the alkylating and cytotoxic activities of the molecule. Accordingly, it could be demonstrated by the reaction of 4-hydroxy-CP with thiols yielding 4-(S-R)-mercapto CP derivatives that the toxication of 4-hydroxy-CP can be controlled under physiologic conditions of pH and temperature. In the case of free protein sulfhydryl groups, this reaction also leads to fixation onto a macromolecule of the CP metabolite. On the basis of these peculiar reactivities of the oxazaphosphorine ring of 4-hydroxy-CP and of the partial reaction kinetics involved during toxication or deactivation, the significance of these findings to the problem of CP specificity is discussed.", "contents": "The problem of oncostatic specificity of cyclophosphamide (NSC-26271): Studies on reactions that control the alkylating and cytotoxic activity. The relatively high oncostatic specificity of cyclophosphamide (CP) in vivo is shown to be due to the cytotoxic specificity of 4-hydroxycyclophosphamide (4-hydroxy-CP), the first product of metabolic activation of CP in the liver. This specificity can be evaluated not only in vivo by measuring the therapeutic index, but also in vitro by determining its cytotoxicity against Yoshida ascites tumor cells. Evidence is given that 4-hydroxy-CP is not an alkylating agent itself, but attains this property only by release of an alkylating N,N-(2-chloroethyl)phosphorodiamic acid moiety and acrolein. The energetic source for this rate-limiting toxication results from the resonance stabilization of the released acrolein. Reactions at the cryptoaldehyde group of 4-hydroxy-CP, which reduce or prevent the resonance stabilization of the 3-carbon unit to be released, lead to a deactivation of the primary metabolite of CP thus reducing or even preventing toxication, and hence influencing both the alkylating and cytotoxic activities of the molecule. Accordingly, it could be demonstrated by the reaction of 4-hydroxy-CP with thiols yielding 4-(S-R)-mercapto CP derivatives that the toxication of 4-hydroxy-CP can be controlled under physiologic conditions of pH and temperature. In the case of free protein sulfhydryl groups, this reaction also leads to fixation onto a macromolecule of the CP metabolite. On the basis of these peculiar reactivities of the oxazaphosphorine ring of 4-hydroxy-CP and of the partial reaction kinetics involved during toxication or deactivation, the significance of these findings to the problem of CP specificity is discussed."} {"id": "PMID:1277207", "title": "Aldophosphamide: synthesis, characterization, and comparison with \"Hohorst's aldophosphamide\".", "content": "Synthesis of aldophosphamide was attempted by many standard aldehyde-forming reactions under a variety of conditions. Trace amounts of aldophosphamide were produced in several of the reactions, as judged by mass-spectral evidence. A stabilized derivative, aldophosphamide semicarbazone, was prepared and characterized by infrared and proton magnetic resonance, and mass spectral analysis) of \"Hohorst's aldophosphamide\" failed to reveal any evidence for the existence of an aldehyde moiety, and thin-layer chromatographic comparison with the synthetic analogs diethylaldophosphamide and diethylhomoaldophosphamide indicated radical differences in migration rates between those of the analogs and that of \"Hohorst's aldophosphamide.\" It is suggested that \"Hohorst's aldophosphamide\" is perhaps a diastereoisomer of 4-hydroxycyclophosphamide or an aldehyde hydrate or hemiacetal with 1,3-propanediol.", "contents": "Aldophosphamide: synthesis, characterization, and comparison with \"Hohorst's aldophosphamide\". Synthesis of aldophosphamide was attempted by many standard aldehyde-forming reactions under a variety of conditions. Trace amounts of aldophosphamide were produced in several of the reactions, as judged by mass-spectral evidence. A stabilized derivative, aldophosphamide semicarbazone, was prepared and characterized by infrared and proton magnetic resonance, and mass spectral analysis) of \"Hohorst's aldophosphamide\" failed to reveal any evidence for the existence of an aldehyde moiety, and thin-layer chromatographic comparison with the synthetic analogs diethylaldophosphamide and diethylhomoaldophosphamide indicated radical differences in migration rates between those of the analogs and that of \"Hohorst's aldophosphamide.\" It is suggested that \"Hohorst's aldophosphamide\" is perhaps a diastereoisomer of 4-hydroxycyclophosphamide or an aldehyde hydrate or hemiacetal with 1,3-propanediol."} {"id": "PMID:1277208", "title": "Studies on the in vivo formation of acrolein: 3-hydroxy-propylmercapturic acid as an index of cyclophosphamide (NSC-26271) activation.", "content": "3-Hydroxypropylmercapturic acid (MCA) has been quantitatively determined in the urine of rats given cyclophosphamide (CP), related antineoplastic agents, allyl alcohol, or acrolein, with a simple procedure involving the use of an amino-acid analyzer. Male rats (300-400 g) injected with CP (50mg [179.1 mumols]/kg of body weight) excreted 16.7 mumols of MCA/kg in their 24-hour urine. Equivalent amounts of isophosphamide produced 9.0; triphosphamide, 16.1; ASTA-5607, 7.2; ASTA-5122, 4.1; and cytoxyl alcohol, 0.4mumols of MCA/kg. From allyl alcohol and acrolein, 26.3 and 19.7 mumols of MCA/kg were obtained respectively. MCA values were directly proportional to drug dose levels. Since acrolein and phosphorodiamidic acid mustard are the toxic decomposition products of aldophosphamide, and acrolein conjugation appears to be the first step for MCA formation values for MCA would reflect active CP levels. The in vitro interaction of acrolein with glutathione, other sulfhydryl compounds, and a few amino acids at concentrations of 0.15 mumols/ml was also studied. The decrease of acrolein's main absorption peak at 209 nm was used to follow its reaction rate. The faster interactions observed were with the sulfhydryl compounds, where a 50% decrease of absorption in interactions with glutathione and cysteine (at pH 7.4 and 23 degrees C) took place in 111 and 30 seconds respectively. Incubation of these adducts at 37 degrees C and 100 degrees C generated acrolein with a maximum recovery yield of 83% at 100 degrees C. Five patients given 1 g of CP iv excreted 6.4-50 mumols of MCA in their urine in 6 hours.", "contents": "Studies on the in vivo formation of acrolein: 3-hydroxy-propylmercapturic acid as an index of cyclophosphamide (NSC-26271) activation. 3-Hydroxypropylmercapturic acid (MCA) has been quantitatively determined in the urine of rats given cyclophosphamide (CP), related antineoplastic agents, allyl alcohol, or acrolein, with a simple procedure involving the use of an amino-acid analyzer. Male rats (300-400 g) injected with CP (50mg [179.1 mumols]/kg of body weight) excreted 16.7 mumols of MCA/kg in their 24-hour urine. Equivalent amounts of isophosphamide produced 9.0; triphosphamide, 16.1; ASTA-5607, 7.2; ASTA-5122, 4.1; and cytoxyl alcohol, 0.4mumols of MCA/kg. From allyl alcohol and acrolein, 26.3 and 19.7 mumols of MCA/kg were obtained respectively. MCA values were directly proportional to drug dose levels. Since acrolein and phosphorodiamidic acid mustard are the toxic decomposition products of aldophosphamide, and acrolein conjugation appears to be the first step for MCA formation values for MCA would reflect active CP levels. The in vitro interaction of acrolein with glutathione, other sulfhydryl compounds, and a few amino acids at concentrations of 0.15 mumols/ml was also studied. The decrease of acrolein's main absorption peak at 209 nm was used to follow its reaction rate. The faster interactions observed were with the sulfhydryl compounds, where a 50% decrease of absorption in interactions with glutathione and cysteine (at pH 7.4 and 23 degrees C) took place in 111 and 30 seconds respectively. Incubation of these adducts at 37 degrees C and 100 degrees C generated acrolein with a maximum recovery yield of 83% at 100 degrees C. Five patients given 1 g of CP iv excreted 6.4-50 mumols of MCA in their urine in 6 hours."} {"id": "PMID:1277209", "title": "Cyclophosphamide (NSC-26271)-related phosphoramide mustards- recent advances and historical perspective.", "content": "The antitumor activity of three of the most phosphoramide mustards, NSC-69947, NSC-72505, and NSC-72510, was compared with that of phosphoramide mustard (NSC-69945), the apparent active metabolite of cyclophosphamide (CP), against the L1210, P388, B16, and Lewis lung tumor systems. This comparison did not reveal any significant differences in the patterns of inhibitory activity predictive of significant advantages in the clinic of any of these compounds over CP or NSC-69945. Attempts to prepare aldophosphamide, the key intermediate in CP metabolism, by oxidation of hydroxyphosphamide under the Sarett reaction conditions lead primarily to 4-ketocyclophosphamide. Under milder conditions the product isolated appears to be the elusive aldophosphamide on the basis of positive alkylating and aldehyde tests, Rf and infrared data, and the formation and characterization of a semicarbazone. The possibility that this product is an equilibrium mixture with the tautomeric 4-hydroxycyclophosphamide has not been as yet defintely ruled out. Sarett oxidation of homohydroxyphosphamide straightforwardly gives the stable analog, homoaldophosphamide. Biologic testing of this putative aldophosphamide in direct comparison with homoaldophosphamide, CP, and NSC-69945 reveals that aldophosphamide is a potent antitumor agent indistinguishable in activity from CP and NSC-69945, whereas homoaldophosphamide is inactive. These results provide confirmatory evidence for the postulated role of aldophosphamide as an intermediate in CP metabolism and suggest, furthermore, that aldophosphamide itself is not active in vivo, requiring transformation to NSC-69945 via beta-elimination of acrolein to exert its antitumor effects. An historical account of the development of the phosphoramide mustard field is also given.", "contents": "Cyclophosphamide (NSC-26271)-related phosphoramide mustards- recent advances and historical perspective. The antitumor activity of three of the most phosphoramide mustards, NSC-69947, NSC-72505, and NSC-72510, was compared with that of phosphoramide mustard (NSC-69945), the apparent active metabolite of cyclophosphamide (CP), against the L1210, P388, B16, and Lewis lung tumor systems. This comparison did not reveal any significant differences in the patterns of inhibitory activity predictive of significant advantages in the clinic of any of these compounds over CP or NSC-69945. Attempts to prepare aldophosphamide, the key intermediate in CP metabolism, by oxidation of hydroxyphosphamide under the Sarett reaction conditions lead primarily to 4-ketocyclophosphamide. Under milder conditions the product isolated appears to be the elusive aldophosphamide on the basis of positive alkylating and aldehyde tests, Rf and infrared data, and the formation and characterization of a semicarbazone. The possibility that this product is an equilibrium mixture with the tautomeric 4-hydroxycyclophosphamide has not been as yet defintely ruled out. Sarett oxidation of homohydroxyphosphamide straightforwardly gives the stable analog, homoaldophosphamide. Biologic testing of this putative aldophosphamide in direct comparison with homoaldophosphamide, CP, and NSC-69945 reveals that aldophosphamide is a potent antitumor agent indistinguishable in activity from CP and NSC-69945, whereas homoaldophosphamide is inactive. These results provide confirmatory evidence for the postulated role of aldophosphamide as an intermediate in CP metabolism and suggest, furthermore, that aldophosphamide itself is not active in vivo, requiring transformation to NSC-69945 via beta-elimination of acrolein to exert its antitumor effects. An historical account of the development of the phosphoramide mustard field is also given."} {"id": "PMID:1277210", "title": "Cyclic phosphoramide mustard (NSC-69945) derivatives of amino acids and peptides.", "content": "The possibilities offered by a combination of the \"latency\" and \"carrier\" principles were studied by joining the phosphoramide mustard group with amino acids. The structures of the resulting derivatives are reminiscent of cyclophosphamide, but they provide feasibility for stereoisomeric modifications and for incorporation into synthetic peptides. Modlel peptides with a different ring system containing cyclic diesters of the N,N-bis(2-chloroethyl)phosphoramidic acid were also constructed. The relative intensities of antitumor activity, toxicity, and antitumor spectrum can be influenced by these molecular manipulations, indicating that the pharmacokinetics, and probably even the enzymatic activation, are markedly dependent upon the overall physiochemical properties and stereochemistry of the molecule. Another approach has been to use larger molecular weight materials as carriers either of the phosphoramide mustard group or the cyclic amino acid derivatives. Both noncovalent and covalent linkages were tried; based on stability properties, conjugates must be regarded as more adequate potential candidates for lysosomotropism.", "contents": "Cyclic phosphoramide mustard (NSC-69945) derivatives of amino acids and peptides. The possibilities offered by a combination of the \"latency\" and \"carrier\" principles were studied by joining the phosphoramide mustard group with amino acids. The structures of the resulting derivatives are reminiscent of cyclophosphamide, but they provide feasibility for stereoisomeric modifications and for incorporation into synthetic peptides. Modlel peptides with a different ring system containing cyclic diesters of the N,N-bis(2-chloroethyl)phosphoramidic acid were also constructed. The relative intensities of antitumor activity, toxicity, and antitumor spectrum can be influenced by these molecular manipulations, indicating that the pharmacokinetics, and probably even the enzymatic activation, are markedly dependent upon the overall physiochemical properties and stereochemistry of the molecule. Another approach has been to use larger molecular weight materials as carriers either of the phosphoramide mustard group or the cyclic amino acid derivatives. Both noncovalent and covalent linkages were tried; based on stability properties, conjugates must be regarded as more adequate potential candidates for lysosomotropism."} {"id": "PMID:1277211", "title": "Deactivation of cyclophosphamide (NSC-26271) metabolites by sulfhydryl compounds.", "content": "The reaction of 4-hydroxycyclophosphamide (4-hydroxy-CP) with sulfhydryl (SH) compounds was studied, and although the cytotoxic activity was lost a significant stabilization of the alkylating capacity was observed at the same time. We were able to show that the reaction of 4-hydroxy-CP with thiols lead to an equilibrium between the reaction product and the starting substrates. On the basis of this equilibrium the increased stabilization of the alkylating capacity of the 4-hydroxy-CP derivatives by raising the SH concentration can be explained. The different degrees of stabilization depending on the structure of the thiol results from different equilibria. the effect on the toxification reaction resulting from this equilibrium, in connection with the tautomeric equilibrium between 4-hydroxy-CP and aldophosphamide, is discussed.", "contents": "Deactivation of cyclophosphamide (NSC-26271) metabolites by sulfhydryl compounds. The reaction of 4-hydroxycyclophosphamide (4-hydroxy-CP) with sulfhydryl (SH) compounds was studied, and although the cytotoxic activity was lost a significant stabilization of the alkylating capacity was observed at the same time. We were able to show that the reaction of 4-hydroxy-CP with thiols lead to an equilibrium between the reaction product and the starting substrates. On the basis of this equilibrium the increased stabilization of the alkylating capacity of the 4-hydroxy-CP derivatives by raising the SH concentration can be explained. The different degrees of stabilization depending on the structure of the thiol results from different equilibria. the effect on the toxification reaction resulting from this equilibrium, in connection with the tautomeric equilibrium between 4-hydroxy-CP and aldophosphamide, is discussed."} {"id": "PMID:1277212", "title": "Stereochemistry, metabolism, and antitumor activity of 4-hydroperoxyisophosphamide (NSC-227114) and its stereoisomer.", "content": "An acid-catalyzed isomerization of 4-hydroperoxyisophosphamide, a synthetic compound with potential antitumor activity, produced a new crystalline epimer having an inverted stereochemistry at the phosphorus atom. The stereochemistry of these epimeric hydroperoxides is discussed on the basis of their chemical and nuclear magnetic resonance properties. The epimers show essentially the same metabolic behavior. This behavior is, however, different from that of isophosphamide (IP) which is metabolized in part via pathways ineffective for its activation. The newly isolated epimer shows slightly higher activity against some kinds of experimental tumors than the original hydroperoxide, suggesting that the inverted stereochemistry of the alkylating group at the phosphorus atom is effective in promoting the antitumor activity of the activated species of IP.", "contents": "Stereochemistry, metabolism, and antitumor activity of 4-hydroperoxyisophosphamide (NSC-227114) and its stereoisomer. An acid-catalyzed isomerization of 4-hydroperoxyisophosphamide, a synthetic compound with potential antitumor activity, produced a new crystalline epimer having an inverted stereochemistry at the phosphorus atom. The stereochemistry of these epimeric hydroperoxides is discussed on the basis of their chemical and nuclear magnetic resonance properties. The epimers show essentially the same metabolic behavior. This behavior is, however, different from that of isophosphamide (IP) which is metabolized in part via pathways ineffective for its activation. The newly isolated epimer shows slightly higher activity against some kinds of experimental tumors than the original hydroperoxide, suggesting that the inverted stereochemistry of the alkylating group at the phosphorus atom is effective in promoting the antitumor activity of the activated species of IP."} {"id": "PMID:1277213", "title": "Importance of pharmacokinetic studies on cyclophosphamide (NSC-26271) in understanding its cytotoxic effect.", "content": "Pharmacokinetic studies on cyclophosphamide (CP) and its alkylating metabolites produced by hepatic biotransformation have been performed in vivo in animals and in vitro in the perfused liver. CP levels were determined by a gas-chromatographic method combined with mass-spectrometry, and production of alkylating metabolites was assayed by the 4-(4-nitrobenzyl)pyridine reaction for alkylating compounds. Differenes in serum drug levels between normal rats and rats bearing Walker 256 carcinosarcoma were observed in vivo and were confirmed by the liver-perfusion technique. Pharmacokinetic parameters and enzyme kinetic data both in normal and in tumor-bearing animals will be presented. The disappearance of CP and the corresponding formation of CP metabolites was significantly modified when (a) CP was given after previous treatment with a compound which alters its biotransformation (ie, phenobarbital, an inducer of microsomal metabolism), (b) CP was given after previous treatment with CP (which inhibits microsomal metablism), or (c) CP was given with competitive substrates of aldehyde oxidase or dehydrogenase (glyceraldehyde, chloral hydrate, and disulfiram). Results obtained in animals or in the perfused liver will be discussed. The significance of this modified CP metabolism in influencing its cytotoxic effect will be discussed and correlations between drug levels and activity will be presented.", "contents": "Importance of pharmacokinetic studies on cyclophosphamide (NSC-26271) in understanding its cytotoxic effect. Pharmacokinetic studies on cyclophosphamide (CP) and its alkylating metabolites produced by hepatic biotransformation have been performed in vivo in animals and in vitro in the perfused liver. CP levels were determined by a gas-chromatographic method combined with mass-spectrometry, and production of alkylating metabolites was assayed by the 4-(4-nitrobenzyl)pyridine reaction for alkylating compounds. Differenes in serum drug levels between normal rats and rats bearing Walker 256 carcinosarcoma were observed in vivo and were confirmed by the liver-perfusion technique. Pharmacokinetic parameters and enzyme kinetic data both in normal and in tumor-bearing animals will be presented. The disappearance of CP and the corresponding formation of CP metabolites was significantly modified when (a) CP was given after previous treatment with a compound which alters its biotransformation (ie, phenobarbital, an inducer of microsomal metabolism), (b) CP was given after previous treatment with CP (which inhibits microsomal metablism), or (c) CP was given with competitive substrates of aldehyde oxidase or dehydrogenase (glyceraldehyde, chloral hydrate, and disulfiram). Results obtained in animals or in the perfused liver will be discussed. The significance of this modified CP metabolism in influencing its cytotoxic effect will be discussed and correlations between drug levels and activity will be presented."} {"id": "PMID:1277214", "title": "Approaches to the pharmacokinetics of cyclophosphamide (NSC 26271): Quantitation of metabolites.", "content": "Recent evidence has implicated phosphoramide mustard as a highly active metabolite of cyclophosphamide (CP). This compound has been shown to be produced from CP both in vitro and in vivo. To further study the role of this active metabolite we have devised methods to quantitate the compound in human serum and urine using gas chromatography-chemical ionization mass spectrometry. Tetradeuterated phosphoramide mustard has been synthesized and is used as an internal standard. CP and nor-nitrogen mustard have also been quantitated in human samples using analogous tetradeuterated internal standards.", "contents": "Approaches to the pharmacokinetics of cyclophosphamide (NSC 26271): Quantitation of metabolites. Recent evidence has implicated phosphoramide mustard as a highly active metabolite of cyclophosphamide (CP). This compound has been shown to be produced from CP both in vitro and in vivo. To further study the role of this active metabolite we have devised methods to quantitate the compound in human serum and urine using gas chromatography-chemical ionization mass spectrometry. Tetradeuterated phosphoramide mustard has been synthesized and is used as an internal standard. CP and nor-nitrogen mustard have also been quantitated in human samples using analogous tetradeuterated internal standards."} {"id": "PMID:1277215", "title": "Sparing effect of cyclophosphamide (NSC-26271) pretreatment on animals lethally treated with gamma-irradiation.", "content": "Cyclophosphamide (CP) can protect mice from gamma-irradiation-induced lethality, the timing of the dose of CP in relation to the irradiation being the critical factor. The most sparing effect is achieved when CP is injected 3 days before irradiation. The protection is mediated by enhanced hemopoietic recovery seen in animals given the most favorable combination ofCP and gamma-irradiation. This rapid recovery cannot be explained by the reduced sensitivity of hemopoietic stem cells after CP treatment to subsequent irradiation although survival of a few radioresistant stem cells cannot be ruled out. Stimulus to repopulate by nonspecific depletion of the bone marrow is not the explanation either, since CP itself appears to play an important role in this effect. The role of the spleen is not critical in this phenomenon and attempts have failed to demonstrate the presence of a humoral factor which can restore bone marrow depleted by gamma-irradiation in the serum of animals treated with CP. CP given 3 days before irradiation appears to result in a purely additive effect against malignant tissue in mice, providing a useful differential kill on tumor tissue at the same time that it provides the maximum protection of normal tissue.", "contents": "Sparing effect of cyclophosphamide (NSC-26271) pretreatment on animals lethally treated with gamma-irradiation. Cyclophosphamide (CP) can protect mice from gamma-irradiation-induced lethality, the timing of the dose of CP in relation to the irradiation being the critical factor. The most sparing effect is achieved when CP is injected 3 days before irradiation. The protection is mediated by enhanced hemopoietic recovery seen in animals given the most favorable combination ofCP and gamma-irradiation. This rapid recovery cannot be explained by the reduced sensitivity of hemopoietic stem cells after CP treatment to subsequent irradiation although survival of a few radioresistant stem cells cannot be ruled out. Stimulus to repopulate by nonspecific depletion of the bone marrow is not the explanation either, since CP itself appears to play an important role in this effect. The role of the spleen is not critical in this phenomenon and attempts have failed to demonstrate the presence of a humoral factor which can restore bone marrow depleted by gamma-irradiation in the serum of animals treated with CP. CP given 3 days before irradiation appears to result in a purely additive effect against malignant tissue in mice, providing a useful differential kill on tumor tissue at the same time that it provides the maximum protection of normal tissue."} {"id": "PMID:1277216", "title": "Identification and pharmacokinetics of cyclophosphamide (NSC-26271) metabolites in vivo.", "content": "The existence of the cyclophosphamide (CP) metabolites, 4-hydroxycyclophosphamide and aldophosphamide, in vivo after application of CP to mice and rats has been demonstrated. The metabolite pattern in the serum and urine of rats at different times after CP application was determined. For this purpose, thin-layer chromatograpic procedure was developed which allows separation of the metabolites without decomposition. Because considerable amounts of radioactivity are bound to serum proteins after 3H-CP application, protein binding studies with CP and CP metabolites were carried out. It was found that 4-hydroxycyclophosphamide is bound to thiol groups of bovine serum albumin yielding a rather stable product which could be isolated by column chromatography on Sephadex.", "contents": "Identification and pharmacokinetics of cyclophosphamide (NSC-26271) metabolites in vivo. The existence of the cyclophosphamide (CP) metabolites, 4-hydroxycyclophosphamide and aldophosphamide, in vivo after application of CP to mice and rats has been demonstrated. The metabolite pattern in the serum and urine of rats at different times after CP application was determined. For this purpose, thin-layer chromatograpic procedure was developed which allows separation of the metabolites without decomposition. Because considerable amounts of radioactivity are bound to serum proteins after 3H-CP application, protein binding studies with CP and CP metabolites were carried out. It was found that 4-hydroxycyclophosphamide is bound to thiol groups of bovine serum albumin yielding a rather stable product which could be isolated by column chromatography on Sephadex."} {"id": "PMID:1277217", "title": "Permeation of cyclophosphamide (NSC-26271) metabolites into tumor cells.", "content": "The permeation kinetics of cyclophosphamide and its metabolites were studied with Ehrlich ascites tumor cells, murine L1210 leukemia cells, and mouse L929 fibroblasts at 1 degrees C. In contrast to carboxyphosphamide and nor-nitrogen mustard, an equipartition of cyclophosphamide and 4-hydroperoxycyclophosphamide was observed in these cells. First experiments have been done to study the efflux of cyclophosphamide and 4-hydroperoxycyclophosphamide after incubation until saturation with Ehrlich ascites tumor cells. Cyclophosphamide could be washed out completely, whereas, 4-hydroperoxyclophosphamide shows an apparent retention in the cell at 37 degrees C.", "contents": "Permeation of cyclophosphamide (NSC-26271) metabolites into tumor cells. The permeation kinetics of cyclophosphamide and its metabolites were studied with Ehrlich ascites tumor cells, murine L1210 leukemia cells, and mouse L929 fibroblasts at 1 degrees C. In contrast to carboxyphosphamide and nor-nitrogen mustard, an equipartition of cyclophosphamide and 4-hydroperoxycyclophosphamide was observed in these cells. First experiments have been done to study the efflux of cyclophosphamide and 4-hydroperoxycyclophosphamide after incubation until saturation with Ehrlich ascites tumor cells. Cyclophosphamide could be washed out completely, whereas, 4-hydroperoxyclophosphamide shows an apparent retention in the cell at 37 degrees C."} {"id": "PMID:1277218", "title": "Studies on 4-hydroperoxycyclophosphamide (NSC-181815): a simple preparation method and its application for the synthesis of a new class of \"activated\" sulfur-containing cyclophosphamide (NSC-26271) derivatives.", "content": "4-Hydroperoxycyclophosphamide was obtained in approximately 20% yield by ozonization of cyclophosphamide in acetone/water at 0 degrees C. It was reduced to 4-hydroxycyclophosphamide, which was treated with several mercaptans to yield compounds of the type 4-(S-R)-mercapto-cyclophosphamide. In the solid state these compounds are stable at room temperature; in aqueous solution they are hydrolyzed to 4-hydroxycyclophosphamide or its tautomer, aldophosphamide. One of the 4-(S-R)-mercapto-cyclophosphamide compounds was tested biologically in vitro against Yoshida ascites tumor cells and showed the same cytotoxic activity as 4-hydroxycyclophosphamide.", "contents": "Studies on 4-hydroperoxycyclophosphamide (NSC-181815): a simple preparation method and its application for the synthesis of a new class of \"activated\" sulfur-containing cyclophosphamide (NSC-26271) derivatives. 4-Hydroperoxycyclophosphamide was obtained in approximately 20% yield by ozonization of cyclophosphamide in acetone/water at 0 degrees C. It was reduced to 4-hydroxycyclophosphamide, which was treated with several mercaptans to yield compounds of the type 4-(S-R)-mercapto-cyclophosphamide. In the solid state these compounds are stable at room temperature; in aqueous solution they are hydrolyzed to 4-hydroxycyclophosphamide or its tautomer, aldophosphamide. One of the 4-(S-R)-mercapto-cyclophosphamide compounds was tested biologically in vitro against Yoshida ascites tumor cells and showed the same cytotoxic activity as 4-hydroxycyclophosphamide."} {"id": "PMID:1277219", "title": "Studies on the metabolism of isopnosphamide (NSC-109724) in man.", "content": "A method is described for the quantitative determination of cyclophosphamide, isophosphamide, and trophosphamide and their stable alkylating metabolites on thin-layer chromatography plates with the aid of 4-pyridinealdehydr-2-benzothiazolylhydrazone (PBH). The method requires only 0.01-0.02 ml of urine from patients treated with high doses of cyclophosphamide of isophosphamide, but a careful standarization is required by using reference substances. In the urine of patients treated with isophosphamide, the 4-carboxy derivative and two different dechloroethyl derivatives resulting from side-chain oxidation are the predominant metabolites determined, next to isophosphamide. Side-chain oxidation may be prevalent. Determination of isophosphamide and its stable alkylating metabolites in the urine of 25 patients shows that the ratio of unchanged isophosphamide to its metabolites varies widely. The mean value of the total amount of PBH-reactive compounds exceeded 50% of the given dose, whereas less than 1% was found to be converted to urine metabolites which release acrolein.", "contents": "Studies on the metabolism of isopnosphamide (NSC-109724) in man. A method is described for the quantitative determination of cyclophosphamide, isophosphamide, and trophosphamide and their stable alkylating metabolites on thin-layer chromatography plates with the aid of 4-pyridinealdehydr-2-benzothiazolylhydrazone (PBH). The method requires only 0.01-0.02 ml of urine from patients treated with high doses of cyclophosphamide of isophosphamide, but a careful standarization is required by using reference substances. In the urine of patients treated with isophosphamide, the 4-carboxy derivative and two different dechloroethyl derivatives resulting from side-chain oxidation are the predominant metabolites determined, next to isophosphamide. Side-chain oxidation may be prevalent. Determination of isophosphamide and its stable alkylating metabolites in the urine of 25 patients shows that the ratio of unchanged isophosphamide to its metabolites varies widely. The mean value of the total amount of PBH-reactive compounds exceeded 50% of the given dose, whereas less than 1% was found to be converted to urine metabolites which release acrolein."} {"id": "PMID:1277221", "title": "Studies on the human pharmacokinetics of isophosphamide (NSC-109724).", "content": "The pharmacokinetics of isophosphamide (IP) in man has been studied using 14C-labeled drug and differential extraction of unchanged drug from metabolites by CHCl3 extraction of plasma and urine. The plasma decay of IP is biphasic with a terminal half-life of 15.2 hours which is twice that reported for cyclophosphamide (CP). The fraction of drug metabolized is 49% for IP compared to 88% reported for CP. This is consistent with the six-times larger pseudometabolic pharmacokinetic rate constant reported for CP (0.26 hr-1) than found by us for IP (0.04 hr-1). The renal clearance for IP (21.3 ml/min) is two times that of CP (10.7 ml/min). In addition to an analysis of the kinetics of disposition and elimination of unchanged IP, an analysis of the pharmacokinetics of total metabolite of IP in plasma and urine was made. A nonlinear pharmacokinetic model which includes a term for biotransformation according to Michaelis and Menten revealed that the total metabolites do not diffuse from a small plasma space of 2.1 liters but are excreted directly via the urine. In contrast to the biexponential plasma decay of single, high-dose IP (5 g/m2), multiple-dose IP (2.4 g/m2/day X 3) shows a monoexponential decay with a half-life of 6.9 hours, a pseudometabolic rate constant of 0.08 hour-1, and a renal clearance of 18.7 ml/minute. The fraction of drug metabolized (79.7%) calculated from the pharmacokinetic parameters agrees with the fraction of drug recovered in urine as total metabolites (72.8%). This is distinctly different from high-dose IP (48.6%) but similar to the fraction of drug metabolized as reported for CP (88.0%). This suggests that the pharmacokinetic transfer constant for IP metabolism is dose dependent, an observation that may be useful in developing new IP regimens.", "contents": "Studies on the human pharmacokinetics of isophosphamide (NSC-109724). The pharmacokinetics of isophosphamide (IP) in man has been studied using 14C-labeled drug and differential extraction of unchanged drug from metabolites by CHCl3 extraction of plasma and urine. The plasma decay of IP is biphasic with a terminal half-life of 15.2 hours which is twice that reported for cyclophosphamide (CP). The fraction of drug metabolized is 49% for IP compared to 88% reported for CP. This is consistent with the six-times larger pseudometabolic pharmacokinetic rate constant reported for CP (0.26 hr-1) than found by us for IP (0.04 hr-1). The renal clearance for IP (21.3 ml/min) is two times that of CP (10.7 ml/min). In addition to an analysis of the kinetics of disposition and elimination of unchanged IP, an analysis of the pharmacokinetics of total metabolite of IP in plasma and urine was made. A nonlinear pharmacokinetic model which includes a term for biotransformation according to Michaelis and Menten revealed that the total metabolites do not diffuse from a small plasma space of 2.1 liters but are excreted directly via the urine. In contrast to the biexponential plasma decay of single, high-dose IP (5 g/m2), multiple-dose IP (2.4 g/m2/day X 3) shows a monoexponential decay with a half-life of 6.9 hours, a pseudometabolic rate constant of 0.08 hour-1, and a renal clearance of 18.7 ml/minute. The fraction of drug metabolized (79.7%) calculated from the pharmacokinetic parameters agrees with the fraction of drug recovered in urine as total metabolites (72.8%). This is distinctly different from high-dose IP (48.6%) but similar to the fraction of drug metabolized as reported for CP (88.0%). This suggests that the pharmacokinetic transfer constant for IP metabolism is dose dependent, an observation that may be useful in developing new IP regimens."} {"id": "PMID:1277222", "title": "Some studies on the distribution and effects of cyclophosphamide (NSC-26271) in normal and neoplastic tissue.", "content": "The gross uptake and intracellula distribution of 32P-cyclophosphamide has been studied in normal and neoplastic rat and mouse tissues. Prolonged alkylation of DNA and RNA occurs over periods of 24 hours in the mouse and 48 hours in the rat, and it is suggested that this may involve slow release of active metabolites from a drug-macromolecule complex. The survival of cells in pulmonary and sc tumors after cyclophosphamide treatment has been studied in situ using a biochemical assay, and the influence of environmental factors at the tumor site has been assessed. The pattern of drug distribution has been studied in large sc tumors, and in one tumor line the drug concentration achieved has been related to estimated cell survival.", "contents": "Some studies on the distribution and effects of cyclophosphamide (NSC-26271) in normal and neoplastic tissue. The gross uptake and intracellula distribution of 32P-cyclophosphamide has been studied in normal and neoplastic rat and mouse tissues. Prolonged alkylation of DNA and RNA occurs over periods of 24 hours in the mouse and 48 hours in the rat, and it is suggested that this may involve slow release of active metabolites from a drug-macromolecule complex. The survival of cells in pulmonary and sc tumors after cyclophosphamide treatment has been studied in situ using a biochemical assay, and the influence of environmental factors at the tumor site has been assessed. The pattern of drug distribution has been studied in large sc tumors, and in one tumor line the drug concentration achieved has been related to estimated cell survival."} {"id": "PMID:1277223", "title": "Distinctive effects of mechlorethamine (NSC-762), cyclophosphamide (NSC-26271), and BCNU (NSC-409962) on transcription in Ehrlich cells.", "content": "Comparisons have been made between mechlorethamine, cyclophosphamide (CP), and BCNU as to the effects of chemotherapeutic drug levels on the transcription of RNA in vivo in Ehrlich cells. Mechlorethamine causes a dose-dependent depression in the synthesis of large Hn RNA transcripts in the nucleus and in the amount of large polysomal mRNA in the cytoplasm without apparent disturbance of polyadenylation and transport. Because of compensating increases in smaller Hn RNA and mRNA chains there is no inhibition of total RNA synthesis. CP seems to accelerate total Hn RNA and mRNA formation but inhibits polyadenylation. CP also produces an excess of short chains with only a minor depression of the synthesis of longer transcripts and messages. BCNU inhibits both RNA synthesis and polyadenylation but without disturbance of the size distribution of the polynucleotide chains. The results with mechlorethamine, in particular, are not easily explained on the basis of premature chain termination at the sites of DNA alkylation.", "contents": "Distinctive effects of mechlorethamine (NSC-762), cyclophosphamide (NSC-26271), and BCNU (NSC-409962) on transcription in Ehrlich cells. Comparisons have been made between mechlorethamine, cyclophosphamide (CP), and BCNU as to the effects of chemotherapeutic drug levels on the transcription of RNA in vivo in Ehrlich cells. Mechlorethamine causes a dose-dependent depression in the synthesis of large Hn RNA transcripts in the nucleus and in the amount of large polysomal mRNA in the cytoplasm without apparent disturbance of polyadenylation and transport. Because of compensating increases in smaller Hn RNA and mRNA chains there is no inhibition of total RNA synthesis. CP seems to accelerate total Hn RNA and mRNA formation but inhibits polyadenylation. CP also produces an excess of short chains with only a minor depression of the synthesis of longer transcripts and messages. BCNU inhibits both RNA synthesis and polyadenylation but without disturbance of the size distribution of the polynucleotide chains. The results with mechlorethamine, in particular, are not easily explained on the basis of premature chain termination at the sites of DNA alkylation."} {"id": "PMID:1277224", "title": "Aspects of the teratology of cyclophosphamide (NSC-26271).", "content": "Wistar-derived rat embryos were most sensitive to maternally administered cyclophosphamide on Days 9.5 and 10.5 of gestation and to chlorambucil on Day 9.5 of gestation. The spectrum of malformations and the dose-response behavior of both drugs were similar. Chlorambucil was three times more potent than cyclophosphamide on an mg/kg basis. The drugs showed additive behavior when administered in combination. The teratogenic effects of the individual or combined drugs were reduced by protective doses of cysteine or glutathione. Studies with analogs of cyclophosphamide have suggested that the whole molecule is involved in teratogenesis.", "contents": "Aspects of the teratology of cyclophosphamide (NSC-26271). Wistar-derived rat embryos were most sensitive to maternally administered cyclophosphamide on Days 9.5 and 10.5 of gestation and to chlorambucil on Day 9.5 of gestation. The spectrum of malformations and the dose-response behavior of both drugs were similar. Chlorambucil was three times more potent than cyclophosphamide on an mg/kg basis. The drugs showed additive behavior when administered in combination. The teratogenic effects of the individual or combined drugs were reduced by protective doses of cysteine or glutathione. Studies with analogs of cyclophosphamide have suggested that the whole molecule is involved in teratogenesis."} {"id": "PMID:1277225", "title": "The use of deuterated analogs in qualitative and quantitative investigations of the metabolism of cyclophosphamide (NSC-26271).", "content": "Ring-deuterated analogs of cyclophosphamide (CP) (4-d2, 5-d, 4,6-d4, and 4,5,6-d6 derivatives) have been used to study the influence of deuterium substitution on the rates of metabolic pathways involving oxidation at C-4, and on the rate of elimination of acrolein from aldophosphamide. The magnitude of the deuterium isotope effect (kH/kD) associated with appropriate C-deuteration has been related to antitumor activity against the ADJ/PC6 murine plasma cell tumor. Isotope effects of 2.2 and 1.8 respectively, for the formation of 4-ketocyclophosphamide (4-keto-CP) and carboxyphosphamide, caused little or no change in antitumor activity (4-d2 and 4,6-d4 analogs compared with CP), but an isotope effect of about 5.3 for the beta-elimination pathway, consequent on 5,5-dideuteration, was paralleled by a marked drop in potency (7-13-fold increase in ED90) of 5,5-dideuterated analogs compared with that of CP. Analogs tetradeuterated in the bis(2-chloroethyl)amino function were used to quantitate CP and 4-keto-CP in human plasma and urine using stable-isotope dilution and direct-insertion electron impact mass spectrometry. The negative optical rotation of CP recovered from human urine after administration of the racemlc drug gave evidence for stereoselectivity in the metabolism.", "contents": "The use of deuterated analogs in qualitative and quantitative investigations of the metabolism of cyclophosphamide (NSC-26271). Ring-deuterated analogs of cyclophosphamide (CP) (4-d2, 5-d, 4,6-d4, and 4,5,6-d6 derivatives) have been used to study the influence of deuterium substitution on the rates of metabolic pathways involving oxidation at C-4, and on the rate of elimination of acrolein from aldophosphamide. The magnitude of the deuterium isotope effect (kH/kD) associated with appropriate C-deuteration has been related to antitumor activity against the ADJ/PC6 murine plasma cell tumor. Isotope effects of 2.2 and 1.8 respectively, for the formation of 4-ketocyclophosphamide (4-keto-CP) and carboxyphosphamide, caused little or no change in antitumor activity (4-d2 and 4,6-d4 analogs compared with CP), but an isotope effect of about 5.3 for the beta-elimination pathway, consequent on 5,5-dideuteration, was paralleled by a marked drop in potency (7-13-fold increase in ED90) of 5,5-dideuterated analogs compared with that of CP. Analogs tetradeuterated in the bis(2-chloroethyl)amino function were used to quantitate CP and 4-keto-CP in human plasma and urine using stable-isotope dilution and direct-insertion electron impact mass spectrometry. The negative optical rotation of CP recovered from human urine after administration of the racemlc drug gave evidence for stereoselectivity in the metabolism."} {"id": "PMID:1277226", "title": "Studies on the disposition of cyclophosphamide (NSC-26271) in tumor-bearing mice by means of gas chromatography-chemical ionization-mass fragmentography.", "content": "The disposition of cyclophosphamide (CP) in mice bearing Lewis lung tumor has been studied by chemical ionization-mass fragmentography using isophosphamide as the internal standard. The drugs were analyzed as their N-trifluoroacetyl derivatives in order to increase sensitivity and to avoid column adsorption and decomposition phenomena. The minimum detectable amount was 500 pg/injection. Linearity was found up to microgram amounts of the substance without any interference of endogenous compounds.", "contents": "Studies on the disposition of cyclophosphamide (NSC-26271) in tumor-bearing mice by means of gas chromatography-chemical ionization-mass fragmentography. The disposition of cyclophosphamide (CP) in mice bearing Lewis lung tumor has been studied by chemical ionization-mass fragmentography using isophosphamide as the internal standard. The drugs were analyzed as their N-trifluoroacetyl derivatives in order to increase sensitivity and to avoid column adsorption and decomposition phenomena. The minimum detectable amount was 500 pg/injection. Linearity was found up to microgram amounts of the substance without any interference of endogenous compounds."} {"id": "PMID:1277227", "title": "Qualitative and quantitative investigations of cyclophosphamide (NSC-26271), cyclophosphamide metabolites, and related compounds by field-desorption mass spectrometry.", "content": "The potential of field-desorption mass spectrometry (FD-MS) coupled with photoplate detection for qualitative and quantitative studies on cyclophosphamide (CP) and its metabolites is reviewed. The characteristic features of this ionization mode are minimal fragmentation of the molecular ion coupled with the capacity to produce such ions from thermally unstable or nonvolatile samples. Since CP is itself extensively fragmented in the electron-impact ionization mode, and since it possesses both thermally unstable (eg, 4-hydroxycyclophosphamide, carboxyphosphamide) as well as ionic and hence nonvolatile metabolites (eg, phosphorodiamidic acid), the FD technique has potential value for the detection and quantitation of the drug and its metabolites in underviatized mixtures. Some of the factors which influence the reproducibility of FD spectra are enumerated. In order to improve the FD technique for quantitative results a device for emission-controlled FD was constructed and its use is described. Three different modes of operation are discussed using the FD spectra of CP conjugates typical for each. Preliminary investigations into the use of the d6 analog of CP for quantitation of the drug by FD-MS are also reported.", "contents": "Qualitative and quantitative investigations of cyclophosphamide (NSC-26271), cyclophosphamide metabolites, and related compounds by field-desorption mass spectrometry. The potential of field-desorption mass spectrometry (FD-MS) coupled with photoplate detection for qualitative and quantitative studies on cyclophosphamide (CP) and its metabolites is reviewed. The characteristic features of this ionization mode are minimal fragmentation of the molecular ion coupled with the capacity to produce such ions from thermally unstable or nonvolatile samples. Since CP is itself extensively fragmented in the electron-impact ionization mode, and since it possesses both thermally unstable (eg, 4-hydroxycyclophosphamide, carboxyphosphamide) as well as ionic and hence nonvolatile metabolites (eg, phosphorodiamidic acid), the FD technique has potential value for the detection and quantitation of the drug and its metabolites in underviatized mixtures. Some of the factors which influence the reproducibility of FD spectra are enumerated. In order to improve the FD technique for quantitative results a device for emission-controlled FD was constructed and its use is described. Three different modes of operation are discussed using the FD spectra of CP conjugates typical for each. Preliminary investigations into the use of the d6 analog of CP for quantitation of the drug by FD-MS are also reported."} {"id": "PMID:1277228", "title": "Characterization of cyclophosphamide (NSC-26271) metabolites and related derivatives by field-desorption and electron-impact mass spectrometry.", "content": "Several important metabolites of cyclophosphamide (CP), such as 4-hydroxycyclophosphamide and phosphoramide mustard, some 4-alkyl(aryl)thio derivatives have been investigated by field-desorption and electron-impact mass spectrometry. The structural identification of synthetic compounds and of derivatives, isolated by thin-layer chromatography in vitro, was possible since complementary information can be obtained using the two ionization techniques. Whereas only the field-desorption mass spectra showed more abundant molecular ions, the electron-impact technique revealed a characteristic fragmentation pattern for most of the compounds studied. Examples are given which demonstrate the existence of stereoisomers of CP derivatives using thin-layer chromatography and field-desorption mass spectrometry. The results indicate that field-desorption mass spectrometry is also a particularly appropriate method for the characterization of unstable CP metabolites in vivo.", "contents": "Characterization of cyclophosphamide (NSC-26271) metabolites and related derivatives by field-desorption and electron-impact mass spectrometry. Several important metabolites of cyclophosphamide (CP), such as 4-hydroxycyclophosphamide and phosphoramide mustard, some 4-alkyl(aryl)thio derivatives have been investigated by field-desorption and electron-impact mass spectrometry. The structural identification of synthetic compounds and of derivatives, isolated by thin-layer chromatography in vitro, was possible since complementary information can be obtained using the two ionization techniques. Whereas only the field-desorption mass spectra showed more abundant molecular ions, the electron-impact technique revealed a characteristic fragmentation pattern for most of the compounds studied. Examples are given which demonstrate the existence of stereoisomers of CP derivatives using thin-layer chromatography and field-desorption mass spectrometry. The results indicate that field-desorption mass spectrometry is also a particularly appropriate method for the characterization of unstable CP metabolites in vivo."} {"id": "PMID:1277229", "title": "X-ray crystallographic studies of cyclophosphamide (NSC-26271) derivatives.", "content": "Molecular structures of 4-hydroperoxycyclophosphamide (4-hydroperoxy-CP) and of two stereoisomers of 4-hydroperoxyisophosphamide (4-hydroperoxy-IP) have been determined by X-ray crystallography. All compounds, synthesized by Dr. A. Takamizawa by ozonolysis of appropriate open-chain precursors, demonstrate in vivo and in vitro cytotoxicity. The structure results show that for 4-hydroperoxy-CP and both isomers of 4-hydroperoxy-IP the 4-hydroperoxy group is situated axial to the ring. In 4-hydroperoxy-CP and the isomer of 4-hydroperoxy-IP which is the major product of the ozonolysis, the phosphoryl oxygen is equatorial to the ring and trans to the C4-oxygen. A scheme is presented to account for the interconversion of the two 4-hydroperoxy-IP configurations. Since a stereoisomer with a hydroperoxy or hydroxy group equatorial has not been isolated from the ozonolysis synthesis or from the Fenton oxidation of cyclophosphamide (CP), the configuration with C4-oxygen axial which is found in 4-hydroperoxy-CP and both isomers of 4-hydroperoxy-I is probably more stable and may be the configuration of 4-hydroxy compounds formed by the in vivo oxidation of CP, isophosphamide, and trophosphamide (TP). The molecular structure of TP has also been elucidated. Comparison of the conformations of the three chloroethyl alkylating groups of this molecule with those of the two chloroethyl groups of other CP derivatives indicates that these groups are highly flexible and do not assume one favored conformation.", "contents": "X-ray crystallographic studies of cyclophosphamide (NSC-26271) derivatives. Molecular structures of 4-hydroperoxycyclophosphamide (4-hydroperoxy-CP) and of two stereoisomers of 4-hydroperoxyisophosphamide (4-hydroperoxy-IP) have been determined by X-ray crystallography. All compounds, synthesized by Dr. A. Takamizawa by ozonolysis of appropriate open-chain precursors, demonstrate in vivo and in vitro cytotoxicity. The structure results show that for 4-hydroperoxy-CP and both isomers of 4-hydroperoxy-IP the 4-hydroperoxy group is situated axial to the ring. In 4-hydroperoxy-CP and the isomer of 4-hydroperoxy-IP which is the major product of the ozonolysis, the phosphoryl oxygen is equatorial to the ring and trans to the C4-oxygen. A scheme is presented to account for the interconversion of the two 4-hydroperoxy-IP configurations. Since a stereoisomer with a hydroperoxy or hydroxy group equatorial has not been isolated from the ozonolysis synthesis or from the Fenton oxidation of cyclophosphamide (CP), the configuration with C4-oxygen axial which is found in 4-hydroperoxy-CP and both isomers of 4-hydroperoxy-I is probably more stable and may be the configuration of 4-hydroxy compounds formed by the in vivo oxidation of CP, isophosphamide, and trophosphamide (TP). The molecular structure of TP has also been elucidated. Comparison of the conformations of the three chloroethyl alkylating groups of this molecule with those of the two chloroethyl groups of other CP derivatives indicates that these groups are highly flexible and do not assume one favored conformation."} {"id": "PMID:1277263", "title": "The influence of dietary protein deficiency on haemopoietic cells in the mouse.", "content": "These experiments examined the effect of a diet limited only in protein (4% by weight) on haemopoietic stem cells in mice. This diet places severe restrictions on growth and cell proliferation and this was reflected in lower numbers of colony forming units (CFUs) and in vitro colony forming cells (CFCs). Differences were apparent in the response of different organs to this stress; for instance, the incidence of spleen CFUs fell sharply from around 40/mg spleen tissue to 1-4/mg spleen tissue after 3 weeks on a low protein diet. This selective loss did not occur in bone marrow where total CFUs remained proportional to cellular content. Yet a third pattern was shown by thymus CFUs--although the numbers were low these increased from 16/thymus in normal mice to 132/thymus in deprived mice. This was the only organ examined which showed an increase. The effects of a return to a high protein (18%) diet showed that the spleen was the most responsive organ. By day 5 after the return to 18% protein the spleen contained as many CFUs per million cells as the bone marrow. During this time the content of CFU in the spleen had increased some 50-fold whereas bone marrow CFUs only doubled. The spleen assumes the major reconstructive role during the refeeding process.", "contents": "The influence of dietary protein deficiency on haemopoietic cells in the mouse. These experiments examined the effect of a diet limited only in protein (4% by weight) on haemopoietic stem cells in mice. This diet places severe restrictions on growth and cell proliferation and this was reflected in lower numbers of colony forming units (CFUs) and in vitro colony forming cells (CFCs). Differences were apparent in the response of different organs to this stress; for instance, the incidence of spleen CFUs fell sharply from around 40/mg spleen tissue to 1-4/mg spleen tissue after 3 weeks on a low protein diet. This selective loss did not occur in bone marrow where total CFUs remained proportional to cellular content. Yet a third pattern was shown by thymus CFUs--although the numbers were low these increased from 16/thymus in normal mice to 132/thymus in deprived mice. This was the only organ examined which showed an increase. The effects of a return to a high protein (18%) diet showed that the spleen was the most responsive organ. By day 5 after the return to 18% protein the spleen contained as many CFUs per million cells as the bone marrow. During this time the content of CFU in the spleen had increased some 50-fold whereas bone marrow CFUs only doubled. The spleen assumes the major reconstructive role during the refeeding process."} {"id": "PMID:1277264", "title": "A technique for determining the proportion of the clonogenic cells in S phase in ENT6 cell cultures and tumors.", "content": "The survival of cultured EMT6 cells was examined after treatment with hydroxyurea (HU) or high specific activity tritiated thymidine (3H-TdR). The concentrations of the agents, duration of exposure to the agents, and post-exposure treatment of the cultures were found to influence the cell survival; the effects of these factors are reported. Conditions were defined under which the proportions of cells killed by HU and by 3H-TdR were the same and were also the same as the proportion of labeled cells seen on autoradiographs of cultures labeled with small doses of 3H-TdR. Under these conditions, either 3H-TdR or HU could be used to determine the proportion of the clonogenic cells in S phase. Single cell suspensions prepared from solid EMT6 tumors were treated in vitro with HU or 3H-TdR, using the conditions found optimal for each agent with cultured cells. The proportion of the tumor cells killed by treatment with HU in vitro was the same as the proportion killed by HU in vivo and as the proportion labeled by 3H-TdR in vivo, and incubation of tumor cell suspensions with HU in vitro appeared to provide a valid measurement of the proportion of clonogeneic tumor cells in S phase. Incubation of tumor cell suspensions with 3H-TdR in vitro proved difficult to perform and the results were relatively unreliable because of severe problems with reutilization of 3H-TdR during the incubation for colony formation.", "contents": "A technique for determining the proportion of the clonogenic cells in S phase in ENT6 cell cultures and tumors. The survival of cultured EMT6 cells was examined after treatment with hydroxyurea (HU) or high specific activity tritiated thymidine (3H-TdR). The concentrations of the agents, duration of exposure to the agents, and post-exposure treatment of the cultures were found to influence the cell survival; the effects of these factors are reported. Conditions were defined under which the proportions of cells killed by HU and by 3H-TdR were the same and were also the same as the proportion of labeled cells seen on autoradiographs of cultures labeled with small doses of 3H-TdR. Under these conditions, either 3H-TdR or HU could be used to determine the proportion of the clonogenic cells in S phase. Single cell suspensions prepared from solid EMT6 tumors were treated in vitro with HU or 3H-TdR, using the conditions found optimal for each agent with cultured cells. The proportion of the tumor cells killed by treatment with HU in vitro was the same as the proportion killed by HU in vivo and as the proportion labeled by 3H-TdR in vivo, and incubation of tumor cell suspensions with HU in vitro appeared to provide a valid measurement of the proportion of clonogeneic tumor cells in S phase. Incubation of tumor cell suspensions with 3H-TdR in vitro proved difficult to perform and the results were relatively unreliable because of severe problems with reutilization of 3H-TdR during the incubation for colony formation."} {"id": "PMID:1277265", "title": "Alterations in 3H-thymidine incorporation into DNA induced by methyl CCNU (1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea) in normal and tumorous tissues in vivo.", "content": "Methyl CCNU produces a suppression of tritiated thymidine (3H-TdR) incorporation into DNA in vivo in normal bone marrow and gastrointestinal tissues which is different in magnitude and duration from that seen in L1210 ascites tumor in the same animals. This suppression and recovery pattern is not seen in animals bearing L1210 ascites tumor resistant to MeCCNU. Where a different pattern of recovery is seen between normal host target tissues and tumor, the pattern can be exploited to increase the cure rate of animals bearing advanced L1210 ascites tumor with properly spaced second doses of MeCCNU. Additional information on the potential toxicity of second doses of MeCCNU can be predicted from knowledge of the time of recovery of DNA synthesis in the normal host target tissues.", "contents": "Alterations in 3H-thymidine incorporation into DNA induced by methyl CCNU (1-(2-chloroethyl)-3-(4-methyl cyclohexyl)-1-nitrosourea) in normal and tumorous tissues in vivo. Methyl CCNU produces a suppression of tritiated thymidine (3H-TdR) incorporation into DNA in vivo in normal bone marrow and gastrointestinal tissues which is different in magnitude and duration from that seen in L1210 ascites tumor in the same animals. This suppression and recovery pattern is not seen in animals bearing L1210 ascites tumor resistant to MeCCNU. Where a different pattern of recovery is seen between normal host target tissues and tumor, the pattern can be exploited to increase the cure rate of animals bearing advanced L1210 ascites tumor with properly spaced second doses of MeCCNU. Additional information on the potential toxicity of second doses of MeCCNU can be predicted from knowledge of the time of recovery of DNA synthesis in the normal host target tissues."} {"id": "PMID:1277266", "title": "The migration of lymphocytes across specialized vascular endothelium. II. The contrasting consequences of treating lymphocytes with tryspin or neuraminidase.", "content": "Lymphocytes were exposed in vitro to either trypsin or neuraminidase. The ability of the treated cells to migrate into tissues were measured (a) by i.v. injection into intact recipients and (b) by vascular perfusion through an isolated lymph-node preparation. The localization of trypsinized cells in the lymph-nodes of recipients was deficient when compared to untreated lymphocytes and there was a surplus of trypsinized cells in blood. Trypsinized cells migrated into the isolated nodes in reduced numbers. By contrast, neuraminidase treated lymphocytes were markedly deficient in the blood of recipients early after injection; their localization in the spleen and lymph-nodes was also deficient but they were in surplus in the liver. Moreover they migrated into the isolated nodes in slightly increased numbers. By 24 hr after injection the perturbed localization pattern produced by either enzyme was partly restored to normal. In conclusion, tryspin interfered with the capacity of lymphocytes to migrate into lymph-nodes but neuraminidase did not; the latter promoted the hepatic sequestration of cells and the reduced localization in the blood and tissues was a consequence of this. The hypothesis that lymphocytes adhere to specialized endothelia in lymph-nodes because of specific glycoside sequences on their surface lacks experimental support.", "contents": "The migration of lymphocytes across specialized vascular endothelium. II. The contrasting consequences of treating lymphocytes with tryspin or neuraminidase. Lymphocytes were exposed in vitro to either trypsin or neuraminidase. The ability of the treated cells to migrate into tissues were measured (a) by i.v. injection into intact recipients and (b) by vascular perfusion through an isolated lymph-node preparation. The localization of trypsinized cells in the lymph-nodes of recipients was deficient when compared to untreated lymphocytes and there was a surplus of trypsinized cells in blood. Trypsinized cells migrated into the isolated nodes in reduced numbers. By contrast, neuraminidase treated lymphocytes were markedly deficient in the blood of recipients early after injection; their localization in the spleen and lymph-nodes was also deficient but they were in surplus in the liver. Moreover they migrated into the isolated nodes in slightly increased numbers. By 24 hr after injection the perturbed localization pattern produced by either enzyme was partly restored to normal. In conclusion, tryspin interfered with the capacity of lymphocytes to migrate into lymph-nodes but neuraminidase did not; the latter promoted the hepatic sequestration of cells and the reduced localization in the blood and tissues was a consequence of this. The hypothesis that lymphocytes adhere to specialized endothelia in lymph-nodes because of specific glycoside sequences on their surface lacks experimental support."} {"id": "PMID:1277267", "title": "The effects of colcemid on mouse bone marrow.", "content": "Following Colcemid administration, mitoses accumulate preferentially in the subendosteal region of the bone marrow of the mouse. This finding suggests that the most rapidly proliferating cells are localized to the subendosteal region, and complements previous radioautographic studies which have demonstrated a corresponding labelling gradient in the marrow. Quantitative estimates of cell cycle time by the stathmokinetic method were precluded by the presence of significant Colcemid induced interphase cell loss. Colcemid also affected cell differentiation in the marrow. Following Colcemid administration there was a fall in mature granulocytes in the marrow, and a concommitant rise in marrow megakaryocytes.", "contents": "The effects of colcemid on mouse bone marrow. Following Colcemid administration, mitoses accumulate preferentially in the subendosteal region of the bone marrow of the mouse. This finding suggests that the most rapidly proliferating cells are localized to the subendosteal region, and complements previous radioautographic studies which have demonstrated a corresponding labelling gradient in the marrow. Quantitative estimates of cell cycle time by the stathmokinetic method were precluded by the presence of significant Colcemid induced interphase cell loss. Colcemid also affected cell differentiation in the marrow. Following Colcemid administration there was a fall in mature granulocytes in the marrow, and a concommitant rise in marrow megakaryocytes."} {"id": "PMID:1277268", "title": "Properties of Go cells: variations in the proliferative response following isoprenaline.", "content": "The proliferative behaviour induced in the acinar cells of the rat submaxillary gland in response to isoprenaline has been used to examine the transit time of cells from a quiescent (Go) state into the S phase. Cumulative 3H-TdR labelling index curves were constructed to determine the mean time interval (Gis time) between stimulation with isoprenaline and entry into the S phase. Data were collected for the proliferative wave induced by three sequential injections of isoprenaline, and the effects of varying the interval between the second and third injections of isoprenaline, and of changing the dose of the drug, were examined. Intervals of 28, 52 and 76 hr between isoprenaline injections resulted in mean Gis times of 16-2, 20-9 and 25-6 hr respectively. It was concluded that the Gis time depended on the recent history of cells with respect to stimulation, but not division. The results are considered in terms of two models, in one of which the time to leave Go is variable, whilst in the other the cells leave Go immediately the stimulus is applied.", "contents": "Properties of Go cells: variations in the proliferative response following isoprenaline. The proliferative behaviour induced in the acinar cells of the rat submaxillary gland in response to isoprenaline has been used to examine the transit time of cells from a quiescent (Go) state into the S phase. Cumulative 3H-TdR labelling index curves were constructed to determine the mean time interval (Gis time) between stimulation with isoprenaline and entry into the S phase. Data were collected for the proliferative wave induced by three sequential injections of isoprenaline, and the effects of varying the interval between the second and third injections of isoprenaline, and of changing the dose of the drug, were examined. Intervals of 28, 52 and 76 hr between isoprenaline injections resulted in mean Gis times of 16-2, 20-9 and 25-6 hr respectively. It was concluded that the Gis time depended on the recent history of cells with respect to stimulation, but not division. The results are considered in terms of two models, in one of which the time to leave Go is variable, whilst in the other the cells leave Go immediately the stimulus is applied."} {"id": "PMID:1277269", "title": "The 'transition probability model' and the regulation of proliferation of human diploid cell cultures during aging.", "content": "Genealogies derived from time-lapse cinemicrophotographic studies of aging human diploid cell cultures were analysed in terms of the 'transition probability' model. It was found that the distribution of intermitotic times obtained from middle passage cells deviated only slightly from that predicted by the model. In contrast, the plot for late passage cultures did not fit the predicted pattern and appeared to be composed of multiple curves. These changes are discussed in reference to cellular senescence as expressed by normal human diploid cells in vitro.", "contents": "The 'transition probability model' and the regulation of proliferation of human diploid cell cultures during aging. Genealogies derived from time-lapse cinemicrophotographic studies of aging human diploid cell cultures were analysed in terms of the 'transition probability' model. It was found that the distribution of intermitotic times obtained from middle passage cells deviated only slightly from that predicted by the model. In contrast, the plot for late passage cultures did not fit the predicted pattern and appeared to be composed of multiple curves. These changes are discussed in reference to cellular senescence as expressed by normal human diploid cells in vitro."} {"id": "PMID:1277270", "title": "Morphology and distribution of supraependymal cells in the third ventricle of the albino rat.", "content": "The supraependymal cells (SEC) are a normal component of the wall of the cerebral ventricles. In the hypothalamic area of the third ventricle they are restricted, in healthy animals, to the ependymal projection of the hypophyseotropic area. Here the SEC show great polymorphism. In addition to bipolar, multipolar and stellate or spider-like cells, transitional forms between these types can be seen. Their perikarya and processes can either remain at some distance from the ependyma or be in close contact with it. The processes may protrude between the ependymal cells or show surface differentiations that resemble the thin cytoplasmic folds of the mesenchymal wandering cells. Considering this and the variations in the number of cells, for example during the ovarian cycle, the SEC can be interpreted as mesenchymal cells, probably related to microglial cells of the subependymal layer. It is suggested that the SEC have a phagocytotic function and may be involved in the normal renewal of the ependyma. A definitive explanation for the restriction of the SEC to the hypophyseotropic area as well as the elucidation of their function remain to be found.", "contents": "Morphology and distribution of supraependymal cells in the third ventricle of the albino rat. The supraependymal cells (SEC) are a normal component of the wall of the cerebral ventricles. In the hypothalamic area of the third ventricle they are restricted, in healthy animals, to the ependymal projection of the hypophyseotropic area. Here the SEC show great polymorphism. In addition to bipolar, multipolar and stellate or spider-like cells, transitional forms between these types can be seen. Their perikarya and processes can either remain at some distance from the ependyma or be in close contact with it. The processes may protrude between the ependymal cells or show surface differentiations that resemble the thin cytoplasmic folds of the mesenchymal wandering cells. Considering this and the variations in the number of cells, for example during the ovarian cycle, the SEC can be interpreted as mesenchymal cells, probably related to microglial cells of the subependymal layer. It is suggested that the SEC have a phagocytotic function and may be involved in the normal renewal of the ependyma. A definitive explanation for the restriction of the SEC to the hypophyseotropic area as well as the elucidation of their function remain to be found."} {"id": "PMID:1277271", "title": "Ultrastructure of the compound eye of the haploid male beetle, Xyleborus ferrugineus.", "content": "The compound eye of male (haploid) Xyleborus ferrugineus beetles was examined with scanning and transmission electron microscopy. The eye externally consists of ca. 19 to 33 facets. Each ommatidium is composed of a thickly biconvex lenslet with about 50 electron dense and rare layers, but at the junction area between two lenslets there are only about 35 to 37 layers that can be distinguished. A very short (3.4-4.0 mum) acone type crystalline cone is located directly beneath the lenslet. Each ommatidium is surrounded by pigment cells, and pigment granules also appear throughout the cytoplasm of the retinular cells. Some pigment granules are even present below the basement membrane. there are 8 retinular cells. The rhabdomeres of 2 centrally situated photoreceptor cells fuse into a rhabdom which is enveloped by the rhabdomeres of 6 peripheral retinular cells. The rhabdomeres of the 6 peripheral retinular cells join laterally to form a rhabdomeric ring around the central rhabdom. No tracheation was observed among the retinular cells. Virus-like particles are evident near the nucleus in each Semper cell of the crystalline cone.", "contents": "Ultrastructure of the compound eye of the haploid male beetle, Xyleborus ferrugineus. The compound eye of male (haploid) Xyleborus ferrugineus beetles was examined with scanning and transmission electron microscopy. The eye externally consists of ca. 19 to 33 facets. Each ommatidium is composed of a thickly biconvex lenslet with about 50 electron dense and rare layers, but at the junction area between two lenslets there are only about 35 to 37 layers that can be distinguished. A very short (3.4-4.0 mum) acone type crystalline cone is located directly beneath the lenslet. Each ommatidium is surrounded by pigment cells, and pigment granules also appear throughout the cytoplasm of the retinular cells. Some pigment granules are even present below the basement membrane. there are 8 retinular cells. The rhabdomeres of 2 centrally situated photoreceptor cells fuse into a rhabdom which is enveloped by the rhabdomeres of 6 peripheral retinular cells. The rhabdomeres of the 6 peripheral retinular cells join laterally to form a rhabdomeric ring around the central rhabdom. No tracheation was observed among the retinular cells. Virus-like particles are evident near the nucleus in each Semper cell of the crystalline cone."} {"id": "PMID:1277272", "title": "Transport of material between the nucleus, the chromatoid body and the Golgi complex in the early spermatids of the rat.", "content": "The movement and transport of material between intranuclear dense particles, the chromatoid body and the Golgi complex have been studied in early spermatids of the rat. The analyses involved observation of living accurately identified cells, time-lapse cinemicrography and electron microscopy. The chromatoid body establishes transient contacts with intranuclear material during early spermiogenesis. The chromatoid body also makes contacts with the Golgi complex. It is suggested that the chromatoid body receives material from the nucleus during the postmeiotic period and particites in the early formation of the acrosomic system.", "contents": "Transport of material between the nucleus, the chromatoid body and the Golgi complex in the early spermatids of the rat. The movement and transport of material between intranuclear dense particles, the chromatoid body and the Golgi complex have been studied in early spermatids of the rat. The analyses involved observation of living accurately identified cells, time-lapse cinemicrography and electron microscopy. The chromatoid body establishes transient contacts with intranuclear material during early spermiogenesis. The chromatoid body also makes contacts with the Golgi complex. It is suggested that the chromatoid body receives material from the nucleus during the postmeiotic period and particites in the early formation of the acrosomic system."} {"id": "PMID:1277273", "title": "Retinohypothalamic pathway in the duck (Anas platyrhynchos).", "content": "Retinohypothalamic connections were studied in the duck after unilateral optic nerve transection using both light and electron microscopic techniques. Degenerated endings of optic fibers were found only in a circumscribed part of the anterior hypothalamic area, i.e. the ventral region of the contralateral suprachiasmatic nucleus. Images of degenerating boutons were observed in frozen sections (method according to Johnstone-Bowsher), and their presence confirmed by electron microscopic examination. These degenerating boutons make synaptic contacts with dendrites or dendritic spines of neurons of the suprachiasmatic nucleus. In the same material, the decussation of the optic chiasma was studied with the light microscope. Uncrossed retinal fibers were found in the marginal optic tract, the basal optic root and occasionally also inthe isthmo-optic tract.", "contents": "Retinohypothalamic pathway in the duck (Anas platyrhynchos). Retinohypothalamic connections were studied in the duck after unilateral optic nerve transection using both light and electron microscopic techniques. Degenerated endings of optic fibers were found only in a circumscribed part of the anterior hypothalamic area, i.e. the ventral region of the contralateral suprachiasmatic nucleus. Images of degenerating boutons were observed in frozen sections (method according to Johnstone-Bowsher), and their presence confirmed by electron microscopic examination. These degenerating boutons make synaptic contacts with dendrites or dendritic spines of neurons of the suprachiasmatic nucleus. In the same material, the decussation of the optic chiasma was studied with the light microscope. Uncrossed retinal fibers were found in the marginal optic tract, the basal optic root and occasionally also inthe isthmo-optic tract."} {"id": "PMID:1277274", "title": "Effect of calcium depletion and subsequent repletion on parathyroids, parafollicular (C) cells and bone in the growing pig.", "content": "The ultrastructure of the chief cells of the parathroid gland and thyroid parafollicular (C) cells and the morphology of bone in calcium depletion and subsequent repletion were examined in young growing pigs. A low calcium diet resulted in osteopenia, increased removal of the cartilaginous core, osteoclasia and osteocytic osteolysis. Subsequent repletion quickly returned bone to normal. In pigs fed the low calcium diet, there was a marked depletion of secretory granules but a striking increase in the number of microtubules in chief cells. Increasing the calcium content of the diet to normal quickly returned the ultrastructural appearance of chief cells to apparent normal. In the initial response to calcium repletion, chief cells exhibited large number of lysosomes and occasionally prominent paracrystalloid bodies. Electron microscopic examination of parafollicular (C) cells of the thyroid gland failed to reveal differences in ultrastructure between test and control pigs. These findings support the view that bone resorption following calcium deficiency may be the result of a secondary hyperparathyroidism rather than of calcium deficiency per se.", "contents": "Effect of calcium depletion and subsequent repletion on parathyroids, parafollicular (C) cells and bone in the growing pig. The ultrastructure of the chief cells of the parathroid gland and thyroid parafollicular (C) cells and the morphology of bone in calcium depletion and subsequent repletion were examined in young growing pigs. A low calcium diet resulted in osteopenia, increased removal of the cartilaginous core, osteoclasia and osteocytic osteolysis. Subsequent repletion quickly returned bone to normal. In pigs fed the low calcium diet, there was a marked depletion of secretory granules but a striking increase in the number of microtubules in chief cells. Increasing the calcium content of the diet to normal quickly returned the ultrastructural appearance of chief cells to apparent normal. In the initial response to calcium repletion, chief cells exhibited large number of lysosomes and occasionally prominent paracrystalloid bodies. Electron microscopic examination of parafollicular (C) cells of the thyroid gland failed to reveal differences in ultrastructure between test and control pigs. These findings support the view that bone resorption following calcium deficiency may be the result of a secondary hyperparathyroidism rather than of calcium deficiency per se."} {"id": "PMID:1277275", "title": "Fine structure of neurons of the arcuate nucleus and median eminence of the hypothalamus of the golden hamster following immobilization.", "content": "The fine structure of arcuate neurons of the arcuate nucleus, the ependymal tanycytes and the contact zone of the median eminence was examined following immobilization, an acute stress which significantly activated the hypothalamo-pituitary-adrenal (HPA) axis. Arcuate neurons of immobilized adult male hamsters displayed morphological indications of heightened activity; the number of lysosomes and dense core vesicles (80-120nm) was increased. A markedly greater number of dense core vesicles was present in axon terminals of the contact zone of the mid-central median eminence and the ventral proximal stalk. Tanycytes of the median eminence exhibited an augmented number of electron dense bodies in both perikarya and end processes. These results indicate that the arcuate neurons, the axons of the contact zone, and the ependymal tanycytes of the hamster medial basal hypothalamus (MBH) may be involved in the response to immobilization.", "contents": "Fine structure of neurons of the arcuate nucleus and median eminence of the hypothalamus of the golden hamster following immobilization. The fine structure of arcuate neurons of the arcuate nucleus, the ependymal tanycytes and the contact zone of the median eminence was examined following immobilization, an acute stress which significantly activated the hypothalamo-pituitary-adrenal (HPA) axis. Arcuate neurons of immobilized adult male hamsters displayed morphological indications of heightened activity; the number of lysosomes and dense core vesicles (80-120nm) was increased. A markedly greater number of dense core vesicles was present in axon terminals of the contact zone of the mid-central median eminence and the ventral proximal stalk. Tanycytes of the median eminence exhibited an augmented number of electron dense bodies in both perikarya and end processes. These results indicate that the arcuate neurons, the axons of the contact zone, and the ependymal tanycytes of the hamster medial basal hypothalamus (MBH) may be involved in the response to immobilization."} {"id": "PMID:1277276", "title": "Ultrastructural studies on the vitellogenesis of Tetrodontophora bielanensis (Waga) (Collembola).", "content": "Vitellogenesis in Tetrodontophora bielanensis (Waga) is of the \"mixed\" type. Part of the yolk material is produced inside the oocyte (autosynthesis), while part is absorbed by micropinocytosis. During antosynthesis polyribosomes, rough endoplasmic reticulum and dictyosomes take part. Regardless of their origin, mature yolk spheres are constructed identically and are composed of three elements: cortex layer, matrix and crystals. Histochemical tests show that polysaccharides are present in the yolk spheres. Lipid droplets have been observed in the ooplasm; they develop without visible contact with any of the organelles. Among the reserve materials the following have been found: rough endoplasmic reticulum, dictyosomes, polyribosomes, mitochondria and a few microtubules.", "contents": "Ultrastructural studies on the vitellogenesis of Tetrodontophora bielanensis (Waga) (Collembola). Vitellogenesis in Tetrodontophora bielanensis (Waga) is of the \"mixed\" type. Part of the yolk material is produced inside the oocyte (autosynthesis), while part is absorbed by micropinocytosis. During antosynthesis polyribosomes, rough endoplasmic reticulum and dictyosomes take part. Regardless of their origin, mature yolk spheres are constructed identically and are composed of three elements: cortex layer, matrix and crystals. Histochemical tests show that polysaccharides are present in the yolk spheres. Lipid droplets have been observed in the ooplasm; they develop without visible contact with any of the organelles. Among the reserve materials the following have been found: rough endoplasmic reticulum, dictyosomes, polyribosomes, mitochondria and a few microtubules."} {"id": "PMID:1277277", "title": "Sperm development in the teleost Oryzias latipes.", "content": "In Oryzias latipes the processes of spermatogenesis and spermiogenesis occur within testicular or germinal cysts which are delimited by a single layer of lobule boundary cells. These cells, in addition to comprising the structural component of the cyst wall, ingest residual bodies cast off by developing spermatids. Therefore, they are deemed to be the homologue of mammalian Sertoli cells. The germ cells within a cyst develop synchronously owing to the presence of intercellular bridges connecting adjacent cells. Since bridges also connect spermatogonia, it seems probable that all of the germ cells within a cyst may form a single syncytium and do not exist as individual cells until the completion of spermiogenesis when the residual bodies are cast off. Significant differences between spermiogenesis in O. latipes and in the related poeciliid teleosts are discussed.", "contents": "Sperm development in the teleost Oryzias latipes. In Oryzias latipes the processes of spermatogenesis and spermiogenesis occur within testicular or germinal cysts which are delimited by a single layer of lobule boundary cells. These cells, in addition to comprising the structural component of the cyst wall, ingest residual bodies cast off by developing spermatids. Therefore, they are deemed to be the homologue of mammalian Sertoli cells. The germ cells within a cyst develop synchronously owing to the presence of intercellular bridges connecting adjacent cells. Since bridges also connect spermatogonia, it seems probable that all of the germ cells within a cyst may form a single syncytium and do not exist as individual cells until the completion of spermiogenesis when the residual bodies are cast off. Significant differences between spermiogenesis in O. latipes and in the related poeciliid teleosts are discussed."} {"id": "PMID:1277278", "title": "Fine structure of the interplatelet area in the gills of the macrophthalmia stage of the river lamprey, Lampetra fluviatilis (L.).", "content": "The interplatelet epithelium of the gills of freshwater and seawater adapted macrophthalmia stages of the river lamprey, Lampetra fluviatilis, was studied by electron microscopy. Three main cell types: basal, ion-excretory and superficial cells were identified and described. Ion-excretory cells were exposed to the environment in sea water but covered by a layer of superficial cells in fresh water. Electron-dense secretory granules in the apex of the cell were more abundant in fresh water. In fresh water, a few of the superficial cells contained numerous mitochondria and were identified as ion-uptake cells. In view of the scarcity of ion-uptake cells, the possibility that the ion-excretory cells are also responsible for ion-uptake in fresh water is discussed. Phagocytic removal of degenerating ion-excretory cells may be an important mechanism for the conservation of materials in a starving animal.", "contents": "Fine structure of the interplatelet area in the gills of the macrophthalmia stage of the river lamprey, Lampetra fluviatilis (L.). The interplatelet epithelium of the gills of freshwater and seawater adapted macrophthalmia stages of the river lamprey, Lampetra fluviatilis, was studied by electron microscopy. Three main cell types: basal, ion-excretory and superficial cells were identified and described. Ion-excretory cells were exposed to the environment in sea water but covered by a layer of superficial cells in fresh water. Electron-dense secretory granules in the apex of the cell were more abundant in fresh water. In fresh water, a few of the superficial cells contained numerous mitochondria and were identified as ion-uptake cells. In view of the scarcity of ion-uptake cells, the possibility that the ion-excretory cells are also responsible for ion-uptake in fresh water is discussed. Phagocytic removal of degenerating ion-excretory cells may be an important mechanism for the conservation of materials in a starving animal."} {"id": "PMID:1277279", "title": "Fine structural observations on the protonephridium of the terrestrial triclad Geoplana pasipha.", "content": "The protonephridial system of the terrestrial triclad Geoplana pasipha was studied by electron microscopy. In general construction it conforms to that of the freshwater planarian Dugesia tigrina (McKanna, 1968, 1968a). Ultrastructural details permit the identification of proximal, collecting, osmoregulatory and nephridiopore regions. Intralumenal material is frequently observed within the tubules, whose cells are always joined by septate junctions. Cilia are numerous and possibly contribute to the flow of water and solutes along the system. Proximal tubules have a peculiar, particulate membrane coat, while a continuous coat, densely stainable with ruthenium red lines the more distal, unciliated tubules.", "contents": "Fine structural observations on the protonephridium of the terrestrial triclad Geoplana pasipha. The protonephridial system of the terrestrial triclad Geoplana pasipha was studied by electron microscopy. In general construction it conforms to that of the freshwater planarian Dugesia tigrina (McKanna, 1968, 1968a). Ultrastructural details permit the identification of proximal, collecting, osmoregulatory and nephridiopore regions. Intralumenal material is frequently observed within the tubules, whose cells are always joined by septate junctions. Cilia are numerous and possibly contribute to the flow of water and solutes along the system. Proximal tubules have a peculiar, particulate membrane coat, while a continuous coat, densely stainable with ruthenium red lines the more distal, unciliated tubules."} {"id": "PMID:1277280", "title": "Further histophysiological observations on the lower esophagus of the rabbit.", "content": "Previous neurohistological studies have been extended to include the structures contained solely or mainly within the junctional esophageal segment which may play an important role in the sphincter mechanism. The main findings were: 1) a progressive cranio-caudal thickening of the muscularis mucosae; 2) a conspicuous thickening of the circular muscle layer; 3) abundant and close interconnections between the esophageal striated fibres and gastric smooth muscle cells; 4) presence of annulo-spiral elastic fibres coiled around bundles of striated musculature; 5) increase of the intramural nerve component, particularly Auerbach's plexus, which consisted of a continuous nervous layer containing twice as many neurocytes as found in the upper esophageal segments; 6) presence of numerous interconnected motor endplates often possessing ultraexpansional fibres and secondary endplates. The findings are discussed with emphasis on functional correlations in order to attain a unitary morpho-functional view.", "contents": "Further histophysiological observations on the lower esophagus of the rabbit. Previous neurohistological studies have been extended to include the structures contained solely or mainly within the junctional esophageal segment which may play an important role in the sphincter mechanism. The main findings were: 1) a progressive cranio-caudal thickening of the muscularis mucosae; 2) a conspicuous thickening of the circular muscle layer; 3) abundant and close interconnections between the esophageal striated fibres and gastric smooth muscle cells; 4) presence of annulo-spiral elastic fibres coiled around bundles of striated musculature; 5) increase of the intramural nerve component, particularly Auerbach's plexus, which consisted of a continuous nervous layer containing twice as many neurocytes as found in the upper esophageal segments; 6) presence of numerous interconnected motor endplates often possessing ultraexpansional fibres and secondary endplates. The findings are discussed with emphasis on functional correlations in order to attain a unitary morpho-functional view."} {"id": "PMID:1277281", "title": "The discrimination of nine different types of synaptic boutons in the fundus striati (Nucleus accumbens septi).", "content": "An attempt has been made to discriminate additional types of synapses than have been previously described in the nucleus accumbens septi of the cat, which can, according to Brockhaus (1942), justifiably be termed the fundus striati due to the fact that it possesses all of the morphological and some of the neurochemical features of the striatum. This was undertaken in order to correlate at least one type of synapse with each different afferent pathway. Nine distinct types of synapses could be differentiated electron microscopically: Type I: axo-spinous synapses with sparse, small, round vesicles which seemed to be the nigro-striatal endings (35%). Type II: axo-somatic or axo-dendritic en passant synapses containing small, round vesicles (3%). Type III: axo-spinous synapses filled with densely-packed, small, round vesicles displaying strong postsynaptic thickenings which seem to be cortico-striatal (17%). Type IV: large axo-spinous synapses with densely-arranged, small, round vesicles contacting larger spines branching off a pedicle (9%). Type V: axo-somatic or axo-dendritic synapses containing large pleomorphic vesicles, probably axon collaterals (1%). Type VI: axo-somatic or axo-dendritic synapses with elongated small vesicles (20 X 45 nm) (3%). Type VII: large axo-somatic or axo-dendritic synapses filled by densely-packed, small, round vesicles (11%). Type VIII: large axo-somatic or axo-dendritic synapses containing loosely-arranged, small, round vesicles (8%). Type IX: axo-somatic or axo-dendritic synapses containing large, round vesicles in a translucent axoplasm (13%).", "contents": "The discrimination of nine different types of synaptic boutons in the fundus striati (Nucleus accumbens septi). An attempt has been made to discriminate additional types of synapses than have been previously described in the nucleus accumbens septi of the cat, which can, according to Brockhaus (1942), justifiably be termed the fundus striati due to the fact that it possesses all of the morphological and some of the neurochemical features of the striatum. This was undertaken in order to correlate at least one type of synapse with each different afferent pathway. Nine distinct types of synapses could be differentiated electron microscopically: Type I: axo-spinous synapses with sparse, small, round vesicles which seemed to be the nigro-striatal endings (35%). Type II: axo-somatic or axo-dendritic en passant synapses containing small, round vesicles (3%). Type III: axo-spinous synapses filled with densely-packed, small, round vesicles displaying strong postsynaptic thickenings which seem to be cortico-striatal (17%). Type IV: large axo-spinous synapses with densely-arranged, small, round vesicles contacting larger spines branching off a pedicle (9%). Type V: axo-somatic or axo-dendritic synapses containing large pleomorphic vesicles, probably axon collaterals (1%). Type VI: axo-somatic or axo-dendritic synapses with elongated small vesicles (20 X 45 nm) (3%). Type VII: large axo-somatic or axo-dendritic synapses filled by densely-packed, small, round vesicles (11%). Type VIII: large axo-somatic or axo-dendritic synapses containing loosely-arranged, small, round vesicles (8%). Type IX: axo-somatic or axo-dendritic synapses containing large, round vesicles in a translucent axoplasm (13%)."} {"id": "PMID:1277282", "title": "Ultrastructure and permeability of lymph node microvasculature in the mouse.", "content": "The microvasculature of lymph nodes and Peyer's patches consists of arterioles, capillaries and venules. The postcapillary segment comprises high-endothelial venules (HE venules) as well as ordinary venules. In order to study the ultrastructure of the microvasculature, particularly with respect to the nature of intercellular junctions, lanthanum and ruthenium red were used as tracers. Furthermore, to evaluate the permeability properties of the different segments of the microvasculature, intravenously injected horseradish peroxidase (HRP; MW: 40,000) was used. All segments of the microvasculature are permeable to HRP. However, the mechanism of transport across the vascular wall varies in the different segments, apparently correlated with a gradual decrease in number of transport vesicles and a gradual attenuation in the sealing of the endothelial cells. Tight junctions are present in arterioles, and it is assumed that HRP reach the basal lamina exclusively by vesicular transport. Incomplete or focal tight junctions are present in the capillaries, and both intercellular and vesicular pathways are observed. In the venules the intercellular pathway seems to be the dominant one, while vesicular transfer is negligible. However, some micropinocytic vesicles in the HE venule endothelial cells probably represent the initial stage of an intracellular digestion.", "contents": "Ultrastructure and permeability of lymph node microvasculature in the mouse. The microvasculature of lymph nodes and Peyer's patches consists of arterioles, capillaries and venules. The postcapillary segment comprises high-endothelial venules (HE venules) as well as ordinary venules. In order to study the ultrastructure of the microvasculature, particularly with respect to the nature of intercellular junctions, lanthanum and ruthenium red were used as tracers. Furthermore, to evaluate the permeability properties of the different segments of the microvasculature, intravenously injected horseradish peroxidase (HRP; MW: 40,000) was used. All segments of the microvasculature are permeable to HRP. However, the mechanism of transport across the vascular wall varies in the different segments, apparently correlated with a gradual decrease in number of transport vesicles and a gradual attenuation in the sealing of the endothelial cells. Tight junctions are present in arterioles, and it is assumed that HRP reach the basal lamina exclusively by vesicular transport. Incomplete or focal tight junctions are present in the capillaries, and both intercellular and vesicular pathways are observed. In the venules the intercellular pathway seems to be the dominant one, while vesicular transfer is negligible. However, some micropinocytic vesicles in the HE venule endothelial cells probably represent the initial stage of an intracellular digestion."} {"id": "PMID:1277283", "title": "Effects of cystic fibrosis serum on the rat parotid gland.", "content": "Injections of serum from human patients with cystic fibrosis into adult rats caused pronounced structural modifications and increased mitotic rate in the parotid gland. Mitotic rate was increased from a low level of 0.02/1,000 acinar cells in parotid glands of adult rats to 6.5/1,000 acinar cells after 2 or 3 days of serum injection. At the light and electron microscopic levels, significant acinar cell atrophy and degranulation were observed. Cellular necrosis, and increases in quantity of lysosome-like dense bodies, mast cells, and macrophages were also detected. These changes are suggestive of tissue response to injurious foreign protein. Furthermore, the fact that normal sera pronounced the same kind of effects (but greatly reduced in extent) strengthens the view that these effects result from the immunologic response of the host organ to foreign antigen. Since, however, the responses of the rat parotid to cystic fibrosis serum were considerably more marked than those elicited by normal serum, the rat parotid may thus have potential usefulness in assaying for the presence of human cystic fibrosis factor.", "contents": "Effects of cystic fibrosis serum on the rat parotid gland. Injections of serum from human patients with cystic fibrosis into adult rats caused pronounced structural modifications and increased mitotic rate in the parotid gland. Mitotic rate was increased from a low level of 0.02/1,000 acinar cells in parotid glands of adult rats to 6.5/1,000 acinar cells after 2 or 3 days of serum injection. At the light and electron microscopic levels, significant acinar cell atrophy and degranulation were observed. Cellular necrosis, and increases in quantity of lysosome-like dense bodies, mast cells, and macrophages were also detected. These changes are suggestive of tissue response to injurious foreign protein. Furthermore, the fact that normal sera pronounced the same kind of effects (but greatly reduced in extent) strengthens the view that these effects result from the immunologic response of the host organ to foreign antigen. Since, however, the responses of the rat parotid to cystic fibrosis serum were considerably more marked than those elicited by normal serum, the rat parotid may thus have potential usefulness in assaying for the presence of human cystic fibrosis factor."} {"id": "PMID:1277284", "title": "Changes in the fine structure of venous endothelium in the rabbit following adrenaline infusion.", "content": "The fine structure of the endothelium lining the femoral and mesenteric veins in the rabbit was examined following the infusion of concentrations of adrenaline varying from 0.5 to 5.0 mug/kg. Control animals were infused with saline. Vesiculation of the endothelial cells was observed following each infusion of adrenaline, the effect being most marked with the highest dose used. It is suggested that this vesiculation may be associated with the release of antihaemophilic globulin and/or plasminogen activator from the endothelial cells.", "contents": "Changes in the fine structure of venous endothelium in the rabbit following adrenaline infusion. The fine structure of the endothelium lining the femoral and mesenteric veins in the rabbit was examined following the infusion of concentrations of adrenaline varying from 0.5 to 5.0 mug/kg. Control animals were infused with saline. Vesiculation of the endothelial cells was observed following each infusion of adrenaline, the effect being most marked with the highest dose used. It is suggested that this vesiculation may be associated with the release of antihaemophilic globulin and/or plasminogen activator from the endothelial cells."} {"id": "PMID:1277285", "title": "Microtubule fascicles in the stem processes of cultured sensory ganglion cells.", "content": "Microtubule fascicles, resembling those characterizing the initial segment of multipolar neurons, have been observed by electron microscopy within and close to the origin of the stem process of some unipolar ganglion cells in explant cultures of embryonic chick dorsal root ganglia. Each fascile comprised 2-6 closely spaced parallel microtubules linked by electron dense cross-bridges. Since similar observations have been made on stem processes in vivo, the possibility that linked microtubules occur commonly in this site is considered. The observations are discussed in relation to a possible correlation between the presence of microtubule fascicles and the initiation of action potentials.", "contents": "Microtubule fascicles in the stem processes of cultured sensory ganglion cells. Microtubule fascicles, resembling those characterizing the initial segment of multipolar neurons, have been observed by electron microscopy within and close to the origin of the stem process of some unipolar ganglion cells in explant cultures of embryonic chick dorsal root ganglia. Each fascile comprised 2-6 closely spaced parallel microtubules linked by electron dense cross-bridges. Since similar observations have been made on stem processes in vivo, the possibility that linked microtubules occur commonly in this site is considered. The observations are discussed in relation to a possible correlation between the presence of microtubule fascicles and the initiation of action potentials."} {"id": "PMID:1277286", "title": "A light and electron microscopic study of the ciliated urn of Phasolosoma agassizii (Sipunculida).", "content": "The free swimming ciliated urn found in the coelomic fluid of Phascolosoma agassizii has been studied by electron microscopy. The urn is a multicellular structure composed of three cell types: (a) ciliated cells which possibly function in capturing cell debris and foreign particles; (b) cupola cells which are capable of phagocytozing latex particles; and (c) lobe cells which are capable of phagocytozing carbon particles. The lobes are separated from the ciliated cells by a semilunar area, with mucoprotein staining characteristics, containing fibrils which appear to be the structural support for the urn. Ciliated cells and lobes are attached to the semilunar area by hemidesmosomes.", "contents": "A light and electron microscopic study of the ciliated urn of Phasolosoma agassizii (Sipunculida). The free swimming ciliated urn found in the coelomic fluid of Phascolosoma agassizii has been studied by electron microscopy. The urn is a multicellular structure composed of three cell types: (a) ciliated cells which possibly function in capturing cell debris and foreign particles; (b) cupola cells which are capable of phagocytozing latex particles; and (c) lobe cells which are capable of phagocytozing carbon particles. The lobes are separated from the ciliated cells by a semilunar area, with mucoprotein staining characteristics, containing fibrils which appear to be the structural support for the urn. Ciliated cells and lobes are attached to the semilunar area by hemidesmosomes."} {"id": "PMID:1277287", "title": "The ultrastructure of the human fetal pineal gland. II. Innervation and cell junctions.", "content": "The innervation of the pineal gland, the cell junctions in this organ and junctions between ependymal cells in the pineal recess were investigated in 27 human fetuses (crown-rump length 30-190 mm). Free nerve boutons containing clear and a few dense core vesicles were present in the pineal parenchyma and in the perivascular spaces. The boutons did not make \"synaptic\" contacts with the pinealocytes. No evidence for the presence of noradrenaline in the vesicles of nerve boutons was found. Gap junctions, intermediate-like junctions and desmosomes were frequently seen between the pinealocytes. Ruthenium red was used in three fetuses as an extracellular marker. The continuous endothelial cells surrounding the capillary lumen were connected by tight junctions. This indicates the presence of a blood-brain barrier. Tight junctions were present between the ependymal cells in the pineal recess. These junctions constitute an extracellular barrier between the pineal and the cerebrospinal fluid.", "contents": "The ultrastructure of the human fetal pineal gland. II. Innervation and cell junctions. The innervation of the pineal gland, the cell junctions in this organ and junctions between ependymal cells in the pineal recess were investigated in 27 human fetuses (crown-rump length 30-190 mm). Free nerve boutons containing clear and a few dense core vesicles were present in the pineal parenchyma and in the perivascular spaces. The boutons did not make \"synaptic\" contacts with the pinealocytes. No evidence for the presence of noradrenaline in the vesicles of nerve boutons was found. Gap junctions, intermediate-like junctions and desmosomes were frequently seen between the pinealocytes. Ruthenium red was used in three fetuses as an extracellular marker. The continuous endothelial cells surrounding the capillary lumen were connected by tight junctions. This indicates the presence of a blood-brain barrier. Tight junctions were present between the ependymal cells in the pineal recess. These junctions constitute an extracellular barrier between the pineal and the cerebrospinal fluid."} {"id": "PMID:1277288", "title": "Studies on silk secretion in the Trichoptera (F. Limmephilidae). II. Structure and amino acid composition of the silk.", "content": "The ultrastructure and amino acid composition of the secreted silk of two species of trichopteran larvae, Pycnopsyche guttifer (Walk.) and Neophylax concinnus McL., were investigated. The spinnerets of these two animals were also examined by scanning electron microscopy. The silk consists of double-stranded, flat ribbons (1-4 mu wide), composed of bundles of 15-25 A filaments. There are two components of the silk: the fiber proper and a surrounding coat thought to be a silk \"gum\". Only the outer coat is positive to the EM PATP technique of Thiery (1967), which indicated the presence of neutral sugars. Amino acid analyses of Pycnopsyche silk show that, like other silks, two predominant amino acids are glycine and serine. Arginine, unexpectedly, is the third most abundant and there are a large number of basic and long side-chain amino acids. X-ray diffraction studies of the silk indicate that it has a less crystalline, more amorphous structure than that of other silks.", "contents": "Studies on silk secretion in the Trichoptera (F. Limmephilidae). II. Structure and amino acid composition of the silk. The ultrastructure and amino acid composition of the secreted silk of two species of trichopteran larvae, Pycnopsyche guttifer (Walk.) and Neophylax concinnus McL., were investigated. The spinnerets of these two animals were also examined by scanning electron microscopy. The silk consists of double-stranded, flat ribbons (1-4 mu wide), composed of bundles of 15-25 A filaments. There are two components of the silk: the fiber proper and a surrounding coat thought to be a silk \"gum\". Only the outer coat is positive to the EM PATP technique of Thiery (1967), which indicated the presence of neutral sugars. Amino acid analyses of Pycnopsyche silk show that, like other silks, two predominant amino acids are glycine and serine. Arginine, unexpectedly, is the third most abundant and there are a large number of basic and long side-chain amino acids. X-ray diffraction studies of the silk indicate that it has a less crystalline, more amorphous structure than that of other silks."} {"id": "PMID:1277289", "title": "The ultrastructure of the cells of Leydig in the white-crowned sparrow (Zonotrichia leucophrys gambelii) in relation to plasma levels of luteinizing hormone and testosterone.", "content": "In male White-crowned Sparrows subjected to 20 h daily photoperiods there is an approximately 3-fold increase in the plasma concentration of luteinizing hormone (LH) on the first long day after which a quasi-stable level is maintained for at least 42 days. This increase is followed by an increase in numbers of cells of Leydig and an enhancement of their steroidogenic features, a decrease in transitional interstitial cells, and an increase in plasma level of testosterone. With the decline in plasma LH, as photorefractoriness develops, the steroidogenic features of the cells of Leydig undergo disorganization. For as yet unexplainable reasons the plasma levels of testosterone decline before the decrease in plasma LH and before the degeneration of the steroidogenic features of the cells of Leydig.", "contents": "The ultrastructure of the cells of Leydig in the white-crowned sparrow (Zonotrichia leucophrys gambelii) in relation to plasma levels of luteinizing hormone and testosterone. In male White-crowned Sparrows subjected to 20 h daily photoperiods there is an approximately 3-fold increase in the plasma concentration of luteinizing hormone (LH) on the first long day after which a quasi-stable level is maintained for at least 42 days. This increase is followed by an increase in numbers of cells of Leydig and an enhancement of their steroidogenic features, a decrease in transitional interstitial cells, and an increase in plasma level of testosterone. With the decline in plasma LH, as photorefractoriness develops, the steroidogenic features of the cells of Leydig undergo disorganization. For as yet unexplainable reasons the plasma levels of testosterone decline before the decrease in plasma LH and before the degeneration of the steroidogenic features of the cells of Leydig."} {"id": "PMID:1277400", "title": "Limitations of the double sucrose gap voltage clamp technique in tension-voltage determinations on frog atrial muscle.", "content": "The purpose of this study was to evaluate the limitations of the double sucrose gap voltage clamp technique in the determination of tension-voltage relationships for frog atrial muscle. Tension-voltage relationships were determined under two conditions. In one case we determined both the tension response and slow inward current associated with an apparent step depolarization (step-clamp) as a function of the magnitude of the step depolarization. In the second case, an action potential was elicited, the voltage clamp was applied early during the plateau phase of the action potential, and the tension response was determined as a function of the clamp potential (action potential-clamp). Under both step-clamp and action potential-clamp conditions, the waveform of the tension response rose to a peak value (Tp) and then decayed with time to a tension that was maintained for the duration of the depolarization. The Tp-clamp potential relationships obtained under step-clamp and action potential-clamp conditions were similar. Microelectrode measurements of transmembrane potential of cells in the \"voltage-clamped\" region of the preparation demonstrated the lack of temporal and spatial voltage control under both step-clamp and action potential-clamp conditions, and also demonstrated that acquisition of spatial voltage control occurred at about the same time that the tension response reached its peak value. These data indicate that this voltage clamp technique does not allow an accurate determination of the so-called phasic tension-voltage relationship in frog atrial muscle because of a lack of temporal and spatial control of voltage during the rising phase of the tension response.", "contents": "Limitations of the double sucrose gap voltage clamp technique in tension-voltage determinations on frog atrial muscle. The purpose of this study was to evaluate the limitations of the double sucrose gap voltage clamp technique in the determination of tension-voltage relationships for frog atrial muscle. Tension-voltage relationships were determined under two conditions. In one case we determined both the tension response and slow inward current associated with an apparent step depolarization (step-clamp) as a function of the magnitude of the step depolarization. In the second case, an action potential was elicited, the voltage clamp was applied early during the plateau phase of the action potential, and the tension response was determined as a function of the clamp potential (action potential-clamp). Under both step-clamp and action potential-clamp conditions, the waveform of the tension response rose to a peak value (Tp) and then decayed with time to a tension that was maintained for the duration of the depolarization. The Tp-clamp potential relationships obtained under step-clamp and action potential-clamp conditions were similar. Microelectrode measurements of transmembrane potential of cells in the \"voltage-clamped\" region of the preparation demonstrated the lack of temporal and spatial voltage control under both step-clamp and action potential-clamp conditions, and also demonstrated that acquisition of spatial voltage control occurred at about the same time that the tension response reached its peak value. These data indicate that this voltage clamp technique does not allow an accurate determination of the so-called phasic tension-voltage relationship in frog atrial muscle because of a lack of temporal and spatial control of voltage during the rising phase of the tension response."} {"id": "PMID:1277401", "title": "Measurements of disordered flows distal to subtotal vascular stenoses in the thoracic aortas of dogs.", "content": "Instantaneous blood velocity measurements employing a constant temperature hot film anemometer were obtained in the region distal to externally enforced, subtotal vascular stenoses in the descending thoracic aortas of anesthetized dogs. Our objectives were to determine alterations in velocity waveforms and energy spectra as the degree of stenosis was increased. We paid particular attention to distinguishing features of the flow which were characteristic of turbulence. Our results indicate that, for the vessels studied, disturbances in the velocity waveforms occur for very minor localized constrictions. The energy spectra follow certain similarity parameters within a restricted region of the distal velocity field. For severe stenoses relatively high levels of energy exist in frequency ranges which previously have been found to produce poststenotic dilation. The measurements suggest that velocity waveforms and energy spectra provide a very early clue to the existence of localized occlusive vascular disease in larger vessels and that, within a limited region distal to a stenosis, the degree of constriction may be estimated by similarity analysis of the energy spectra.", "contents": "Measurements of disordered flows distal to subtotal vascular stenoses in the thoracic aortas of dogs. Instantaneous blood velocity measurements employing a constant temperature hot film anemometer were obtained in the region distal to externally enforced, subtotal vascular stenoses in the descending thoracic aortas of anesthetized dogs. Our objectives were to determine alterations in velocity waveforms and energy spectra as the degree of stenosis was increased. We paid particular attention to distinguishing features of the flow which were characteristic of turbulence. Our results indicate that, for the vessels studied, disturbances in the velocity waveforms occur for very minor localized constrictions. The energy spectra follow certain similarity parameters within a restricted region of the distal velocity field. For severe stenoses relatively high levels of energy exist in frequency ranges which previously have been found to produce poststenotic dilation. The measurements suggest that velocity waveforms and energy spectra provide a very early clue to the existence of localized occlusive vascular disease in larger vessels and that, within a limited region distal to a stenosis, the degree of constriction may be estimated by similarity analysis of the energy spectra."} {"id": "PMID:1277402", "title": "Neurogenic sympathetic vasoconstriction of the rabbit basilar artery.", "content": "When examined by fluorescence microscopy the rabbit basilar artery contains a rich adrenergic-like plexus at the adventitiomedial junction. The fluorescence disappears upon chronic reserpinization and bilateral superior cervical ganglionectomy. Transmural stimulation of intramural nerves a results in a response which is predominantly constrictor but also contains a small, inconstant dilator component. The constrictor response is abolished by chronic reserpinization, bilateral superior cervical ganglionectomy, and cold storage of the preparation. The constriction is prevented by the adrenergic neuron blocking agents guanethidine and bretylium but not by such alpha-adrenergic receptor blocking agents as phenoxybenzamine (PBZ), phentolamine, and tolazoline. Our results show that doses of the three latter agents sufficient to abolish contractions to norepinephrine (NE) in concentrations of up to 10(-2) M only potentiate and prolong the contractile response to nerve stimulation. The beta-adrenergic receptor blocking agent, propranolol, and inhibitors of NE neuronal uptake, such as desipramine (desmethylimipramine, DMI) and cocaine, do not influence the size of the neurogenic response. These results suggest that the vasoconstrictor component of the rabbit basilar artery response to transmural nerve stimulation (TNS) is mediated via sympathetic adrenergic-like neurons, but at the same time also raise the question whether the transmission process is typical of classic adrenergic neuroeffector mechanisms.", "contents": "Neurogenic sympathetic vasoconstriction of the rabbit basilar artery. When examined by fluorescence microscopy the rabbit basilar artery contains a rich adrenergic-like plexus at the adventitiomedial junction. The fluorescence disappears upon chronic reserpinization and bilateral superior cervical ganglionectomy. Transmural stimulation of intramural nerves a results in a response which is predominantly constrictor but also contains a small, inconstant dilator component. The constrictor response is abolished by chronic reserpinization, bilateral superior cervical ganglionectomy, and cold storage of the preparation. The constriction is prevented by the adrenergic neuron blocking agents guanethidine and bretylium but not by such alpha-adrenergic receptor blocking agents as phenoxybenzamine (PBZ), phentolamine, and tolazoline. Our results show that doses of the three latter agents sufficient to abolish contractions to norepinephrine (NE) in concentrations of up to 10(-2) M only potentiate and prolong the contractile response to nerve stimulation. The beta-adrenergic receptor blocking agent, propranolol, and inhibitors of NE neuronal uptake, such as desipramine (desmethylimipramine, DMI) and cocaine, do not influence the size of the neurogenic response. These results suggest that the vasoconstrictor component of the rabbit basilar artery response to transmural nerve stimulation (TNS) is mediated via sympathetic adrenergic-like neurons, but at the same time also raise the question whether the transmission process is typical of classic adrenergic neuroeffector mechanisms."} {"id": "PMID:1277403", "title": "Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier.", "content": "Acute hypertension was induced in 19 anesthetized cats by the intravenous administration of angiotensin. The caliber of pial arteries was measured by a television image-splitting technique and local cerebral blood flow by the hydrogen clearance technique. As the blood pressure was increased, pail arterioles constricted and cerebral blood flow remained relatively constant, showing that autoregulation of cerebral blood flow was intact. At mean arterial pressures of more than 170 mm Hg arteriolar dilation appeared. In smaller arterioles (initial diameter less than 100 mum) a segmental dilation (the \"sausage'string\" phenomenon) frequently preceded uniform dilation. This arteriolar dilation was associated with a marked increase in local cerebral blood flow indicating that the upper level of autoregulation had been breached. In no cat was vasospasm or a decrease in blood flow observed during induced hypertension. Hypertension also caused dysfunction of the bloodbrain barrier since, in 17 out of 19 of the cats examined, there was extravasation of protein-bound Evans blue into brain tissue. In only one of the 19 cats subjected to neuropathological analysis was ischemic brain damage identified and this was restricted to minimal ischemic cell change. The results indicate that severe, induced hypertension in cats produces cerebral arteriolar dilation, an increase of cerebral blood flow, and dysfunction of the blood-brain barrier. These observations may be of importance in understanding the pathogenesis of hypertensive encephalopathy.", "contents": "Effects of acutely induced hypertension in cats on pial arteriolar caliber, local cerebral blood flow, and the blood-brain barrier. Acute hypertension was induced in 19 anesthetized cats by the intravenous administration of angiotensin. The caliber of pial arteries was measured by a television image-splitting technique and local cerebral blood flow by the hydrogen clearance technique. As the blood pressure was increased, pail arterioles constricted and cerebral blood flow remained relatively constant, showing that autoregulation of cerebral blood flow was intact. At mean arterial pressures of more than 170 mm Hg arteriolar dilation appeared. In smaller arterioles (initial diameter less than 100 mum) a segmental dilation (the \"sausage'string\" phenomenon) frequently preceded uniform dilation. This arteriolar dilation was associated with a marked increase in local cerebral blood flow indicating that the upper level of autoregulation had been breached. In no cat was vasospasm or a decrease in blood flow observed during induced hypertension. Hypertension also caused dysfunction of the bloodbrain barrier since, in 17 out of 19 of the cats examined, there was extravasation of protein-bound Evans blue into brain tissue. In only one of the 19 cats subjected to neuropathological analysis was ischemic brain damage identified and this was restricted to minimal ischemic cell change. The results indicate that severe, induced hypertension in cats produces cerebral arteriolar dilation, an increase of cerebral blood flow, and dysfunction of the blood-brain barrier. These observations may be of importance in understanding the pathogenesis of hypertensive encephalopathy."} {"id": "PMID:1277404", "title": "Physiological loading of isolated mammalian cardiac muscle.", "content": "Cat papillary muscles were subjected to a complex loading function resulting from an analysis of the heart as a pump. The papillary muscle was assumed to be a hypothetical bundle of circumferential muscle fibers in the wall of a simplified cylindrical ventricle. The loading included inertial, resistive, and capacitive components of the cardiovascular system. Changes of ventricular dimensions were taken into account by application of a Laplace relationship. When this complex dynamic loading function was imposed on a shortening muscle by means of an electromagnetic feedback system, the developed force continuously changed with time. The time course of this changing force corresponded to the time course of calculated stress in the intact ejecting heart. Directly displayed force-velocity loops also were similar to loops obtained for the intact heart. Loads proportional to velocity of shortening (damping), acceleration of shortening (inertia), and to the square of shortening velocity (Bernoulli) were investigated separately. Cardiac muscle appeared rather insensitive to inertial loads, and the contribution of inertial loads in the early phase of a contraction under physiological pump loading was minimal. Moreover, during all these dynamic loadings, as long as loading was dynamically increasing or decreasing, velocity of shortening was respectively lower or higher at any muscle length and total load, when compared to velocity at the same length and load under static (constant preload and afterload only) loading.", "contents": "Physiological loading of isolated mammalian cardiac muscle. Cat papillary muscles were subjected to a complex loading function resulting from an analysis of the heart as a pump. The papillary muscle was assumed to be a hypothetical bundle of circumferential muscle fibers in the wall of a simplified cylindrical ventricle. The loading included inertial, resistive, and capacitive components of the cardiovascular system. Changes of ventricular dimensions were taken into account by application of a Laplace relationship. When this complex dynamic loading function was imposed on a shortening muscle by means of an electromagnetic feedback system, the developed force continuously changed with time. The time course of this changing force corresponded to the time course of calculated stress in the intact ejecting heart. Directly displayed force-velocity loops also were similar to loops obtained for the intact heart. Loads proportional to velocity of shortening (damping), acceleration of shortening (inertia), and to the square of shortening velocity (Bernoulli) were investigated separately. Cardiac muscle appeared rather insensitive to inertial loads, and the contribution of inertial loads in the early phase of a contraction under physiological pump loading was minimal. Moreover, during all these dynamic loadings, as long as loading was dynamically increasing or decreasing, velocity of shortening was respectively lower or higher at any muscle length and total load, when compared to velocity at the same length and load under static (constant preload and afterload only) loading."} {"id": "PMID:1277405", "title": "Compression of the coronary arteries by the fibrillating canine heart.", "content": "We performed experiments to test whether the subendocardial ischemia which reportedly accompanies elective ventricular fibrillation (VF) during cardiopulmonary bypass might be the result of mechanical compression of the coronary vessels. The left coronary artery of the open-chest, anesthetized dog was cannulated and perfused with arterial blood through an extracorporeal circuit. Coronary inflow rate was held constant with a pump and the coronary vessels were dilated maximally by infusing adenosine. Any change in perfusion pressure or the transmural distribution of flow in these hearts would have been due to changes in compression. When the hearts were stopped in diastole by vagal stimulation, infusion of microspheres 15 mum in diameter revealed a subendocardial to subepicardial (inner to outer) flow ratio (I/O) of 1.2. When the same hearts were caused to fibrillate spontaneously (not electrically maintained) the I/O fell to 0.9. Little change in coronary perfusion pressure occurred between arrest and VF. When the contractile activity during VF was attenuated by intracoronary sodium pentobarbital (120 mg) the I/O rose toward that seen during arrest. However, augmentation of muscle activity by infusion of isoproterenol during VF failed to change the I/O. Finally the I/O fell in proportion to the degree of distention in the fibrillating ventricle. The results that we observed indicate that muscular contraction during VF preferentially inhibits subendocardial flow through vascular compression.", "contents": "Compression of the coronary arteries by the fibrillating canine heart. We performed experiments to test whether the subendocardial ischemia which reportedly accompanies elective ventricular fibrillation (VF) during cardiopulmonary bypass might be the result of mechanical compression of the coronary vessels. The left coronary artery of the open-chest, anesthetized dog was cannulated and perfused with arterial blood through an extracorporeal circuit. Coronary inflow rate was held constant with a pump and the coronary vessels were dilated maximally by infusing adenosine. Any change in perfusion pressure or the transmural distribution of flow in these hearts would have been due to changes in compression. When the hearts were stopped in diastole by vagal stimulation, infusion of microspheres 15 mum in diameter revealed a subendocardial to subepicardial (inner to outer) flow ratio (I/O) of 1.2. When the same hearts were caused to fibrillate spontaneously (not electrically maintained) the I/O fell to 0.9. Little change in coronary perfusion pressure occurred between arrest and VF. When the contractile activity during VF was attenuated by intracoronary sodium pentobarbital (120 mg) the I/O rose toward that seen during arrest. However, augmentation of muscle activity by infusion of isoproterenol during VF failed to change the I/O. Finally the I/O fell in proportion to the degree of distention in the fibrillating ventricle. The results that we observed indicate that muscular contraction during VF preferentially inhibits subendocardial flow through vascular compression."} {"id": "PMID:1277406", "title": "Studies on the nature of a prostaglandin receptor in canine and rabbit vascular smooth muscle.", "content": "The contractile response of rabbit renal arteries and canine tibial arteries to prostaglandins A2, B2, F2alpha, E1, E2, D2, and B1 was associated with a reduction in total sulfhydryl group content of smooth muscle. The total sulfhydryl content of rabbit renal and canine tibial arteries and was not affected by norepinephrine or potassium chloride. Reduction of disulfide groups with dithiothreitol (DTT) selectively inhibited contractile responses to angiotensin and prostaglandins; 5,5'-Dithiobisnitrobenzoic acid (DTNB), a sulfhydryl group-oxidizing agent, reversed the inhibitory effect of DTT on the contractile responses to prostaglandins. Alkylation of free sulfhydryl groups with ethacrynic acid did not affect the contractile response of isolated canine tibial or rabbit renal arteries to any agonist studied. Ethacrynic acid added to muscle strips exposed to DTT resulted in alkylation of sulfhydryl groups produced by reduction of disulfide bonds and irreversibly prevented DTNB-induced reversal of DTT inhibition of contractile responses to prostaglandins. However, addition of ethacrynic acid to muscle strips contracted by prostaglandins did not inhibit subsequent responses to these acidic lipids. These findings support the hypothesis that contractile responses of rabbit renal and canine tibial arteries to prostaglandins are dependent on interactions between prostaglandins and disulfide groups located in or on the vascular smooth muscle cell, and the concept that membrane disulfide groups may be integral components of vascular smooth muscle receptors for prostaglandins.", "contents": "Studies on the nature of a prostaglandin receptor in canine and rabbit vascular smooth muscle. The contractile response of rabbit renal arteries and canine tibial arteries to prostaglandins A2, B2, F2alpha, E1, E2, D2, and B1 was associated with a reduction in total sulfhydryl group content of smooth muscle. The total sulfhydryl content of rabbit renal and canine tibial arteries and was not affected by norepinephrine or potassium chloride. Reduction of disulfide groups with dithiothreitol (DTT) selectively inhibited contractile responses to angiotensin and prostaglandins; 5,5'-Dithiobisnitrobenzoic acid (DTNB), a sulfhydryl group-oxidizing agent, reversed the inhibitory effect of DTT on the contractile responses to prostaglandins. Alkylation of free sulfhydryl groups with ethacrynic acid did not affect the contractile response of isolated canine tibial or rabbit renal arteries to any agonist studied. Ethacrynic acid added to muscle strips exposed to DTT resulted in alkylation of sulfhydryl groups produced by reduction of disulfide bonds and irreversibly prevented DTNB-induced reversal of DTT inhibition of contractile responses to prostaglandins. However, addition of ethacrynic acid to muscle strips contracted by prostaglandins did not inhibit subsequent responses to these acidic lipids. These findings support the hypothesis that contractile responses of rabbit renal and canine tibial arteries to prostaglandins are dependent on interactions between prostaglandins and disulfide groups located in or on the vascular smooth muscle cell, and the concept that membrane disulfide groups may be integral components of vascular smooth muscle receptors for prostaglandins."} {"id": "PMID:1277407", "title": "Spontaneous action potentials of cells in the canine sinus node.", "content": "Right atria were excised from the hearts of 20 young dogs (15 +/- 5 weeks old) and maintained in vitro in order to perform microelectrode impalements. The atria contracted spontaneously for at least 6 hours at a stable rate of 127/min when they were perfused with Krebs-Ringer bicarbonate solution through the sinus node artery. Cells within a small area near the sinus node artery and between the superior vena cava and right atrium consistently yielded transmembrane potentials typical of pacemaker cells. This area was verified histologically to be the midportion of the sinus node. Electrical characteristics of these sinus node pacemaker cells were: maximum diastolic potential, -56 +/- 7 mV (mean +/- 1 SD); action potential amplitude, 56 +/- 8 mV; overshoot, 0 +/- 2 mV. Smooth transitions from phase 4 to phase 0 were always present. From these experiments we conclude that the excised perfused canine right atrium provides a useful new experimental cardiac preparation because it maintains stable spontaneous activity for many hours in vitro and the sinus node within it is readily accessible for study by intracellular microelectrodes.", "contents": "Spontaneous action potentials of cells in the canine sinus node. Right atria were excised from the hearts of 20 young dogs (15 +/- 5 weeks old) and maintained in vitro in order to perform microelectrode impalements. The atria contracted spontaneously for at least 6 hours at a stable rate of 127/min when they were perfused with Krebs-Ringer bicarbonate solution through the sinus node artery. Cells within a small area near the sinus node artery and between the superior vena cava and right atrium consistently yielded transmembrane potentials typical of pacemaker cells. This area was verified histologically to be the midportion of the sinus node. Electrical characteristics of these sinus node pacemaker cells were: maximum diastolic potential, -56 +/- 7 mV (mean +/- 1 SD); action potential amplitude, 56 +/- 8 mV; overshoot, 0 +/- 2 mV. Smooth transitions from phase 4 to phase 0 were always present. From these experiments we conclude that the excised perfused canine right atrium provides a useful new experimental cardiac preparation because it maintains stable spontaneous activity for many hours in vitro and the sinus node within it is readily accessible for study by intracellular microelectrodes."} {"id": "PMID:1277408", "title": "Evidence for an adenosine receptor on the surface of dog coronary myocytes.", "content": "Adenosine and theophylline were linked covalently to oxidized stachyose to produce compounds too large to penetrate cell membranes. These compounds were used in two conscious and six open-chest anesthetized dogs to test the hypothesis that there is an adenosine receptor on the surface of the coronary myocyte. Intracoronary infusions of the adenosine derivative produced dose-dependent coronary vasodilation which was antagonized by theophylline; two types of theophylline derivative antagonized the coronary vasodilatory action of adenosine. Although these results show that both adenosine and theophylline exert their coronary effects at the surface of the smooth muscle cells, this evidence does not establish that they are competing for a common receptor.", "contents": "Evidence for an adenosine receptor on the surface of dog coronary myocytes. Adenosine and theophylline were linked covalently to oxidized stachyose to produce compounds too large to penetrate cell membranes. These compounds were used in two conscious and six open-chest anesthetized dogs to test the hypothesis that there is an adenosine receptor on the surface of the coronary myocyte. Intracoronary infusions of the adenosine derivative produced dose-dependent coronary vasodilation which was antagonized by theophylline; two types of theophylline derivative antagonized the coronary vasodilatory action of adenosine. Although these results show that both adenosine and theophylline exert their coronary effects at the surface of the smooth muscle cells, this evidence does not establish that they are competing for a common receptor."} {"id": "PMID:1277409", "title": "Action potentials in chick atria. Ontogenetic changes in the dependence of tetrodotoxin-resistant action potentials on calcium, strontium, barium.", "content": "Action potentials were recorded from chick embryo atrial muscle cells bathed in Tyrode's solution. Tetrodotoxin (TTX), 3.1 muM, was added to block the early, transient, Na+-dependent conductance system. Rectangular stimuli were used to evoke action potentials the peak amplitude (Ep) of which depend on the external concentration of divalent cations, [Me2+]0. The relationship between Ep and [Me2+]0 shifted to the right with increasing age. For example, the slope of Ep was 33 +/- 2,22 +/- 1 and 11 +/- 3 mV per 10-fold change in [Ca2+]0 on the 9th, 12th, and 18th incubation days, respectively. In solutions with reduced [Ca2+]0, Ep increased when Ba2+ or Sr2+ was added to the bath. The potency of Me2+ in generating action potentials was Ba2+ greater than Sr2+ greater than Ca2+ and this sequence did not change during development. Action potential amplitude, which was reduced in 18-day preparations, was increased by isoproterenol (increased Ca2+ conductance, gCa2+) and by tetraethylammonium (TEA) ion (decreased K+ conductance, gK). The results show that (1) Me2+-dependent action potentials support membrane excitation in chick atrial cells treated with TTX, and (2) the ability of Me2+ to support action potentials decreases during ontogenesis. We conclude from these experiments that the ontogenetically related decrease in Me2+-induced action potentials is the result of a reduction in gMe2+/gK+ during stimulation.", "contents": "Action potentials in chick atria. Ontogenetic changes in the dependence of tetrodotoxin-resistant action potentials on calcium, strontium, barium. Action potentials were recorded from chick embryo atrial muscle cells bathed in Tyrode's solution. Tetrodotoxin (TTX), 3.1 muM, was added to block the early, transient, Na+-dependent conductance system. Rectangular stimuli were used to evoke action potentials the peak amplitude (Ep) of which depend on the external concentration of divalent cations, [Me2+]0. The relationship between Ep and [Me2+]0 shifted to the right with increasing age. For example, the slope of Ep was 33 +/- 2,22 +/- 1 and 11 +/- 3 mV per 10-fold change in [Ca2+]0 on the 9th, 12th, and 18th incubation days, respectively. In solutions with reduced [Ca2+]0, Ep increased when Ba2+ or Sr2+ was added to the bath. The potency of Me2+ in generating action potentials was Ba2+ greater than Sr2+ greater than Ca2+ and this sequence did not change during development. Action potential amplitude, which was reduced in 18-day preparations, was increased by isoproterenol (increased Ca2+ conductance, gCa2+) and by tetraethylammonium (TEA) ion (decreased K+ conductance, gK). The results show that (1) Me2+-dependent action potentials support membrane excitation in chick atrial cells treated with TTX, and (2) the ability of Me2+ to support action potentials decreases during ontogenesis. We conclude from these experiments that the ontogenetically related decrease in Me2+-induced action potentials is the result of a reduction in gMe2+/gK+ during stimulation."} {"id": "PMID:1277411", "title": "Esophageal echocardiography.", "content": "Esophageal echocardiography has been developed for use in patients with chronic obstructive pulmonary disease and is a safe diagnostic procedure which provides high resolution mirror image echoes of many cardiac structures. Conventional anterior and esophageal echocardiograms were performed in 38 subjects. Esophageal echoes were of diagnostic quality in all 38 subjects, anterior echoes were of diagnostic quality in only 18. Measurements from anterior and esophageal echocardiograms correlated well for aortic valve diameter (r = 0.87), left atrium diameter (r = 0.96), mitral valve EF slope (r = 0.97) and less well for aortic root diameter (r = 0.69).", "contents": "Esophageal echocardiography. Esophageal echocardiography has been developed for use in patients with chronic obstructive pulmonary disease and is a safe diagnostic procedure which provides high resolution mirror image echoes of many cardiac structures. Conventional anterior and esophageal echocardiograms were performed in 38 subjects. Esophageal echoes were of diagnostic quality in all 38 subjects, anterior echoes were of diagnostic quality in only 18. Measurements from anterior and esophageal echocardiograms correlated well for aortic valve diameter (r = 0.87), left atrium diameter (r = 0.96), mitral valve EF slope (r = 0.97) and less well for aortic root diameter (r = 0.69)."} {"id": "PMID:1277412", "title": "The natural history of truncus arteriosus.", "content": "The cases of 23 patients whose condition was diagnosed as truncus arteriosus, type I or II, and who were seen at the Mayo Clinic during the decade preceding 1967, that is, before corrective operation became feasible, were reviewed. Ten were infants (through one year of age), and all ten have died. Eight ranged in age from more than one year through seven years of age, and all are living, except one, who diet 11 years after diagnosis. Five were older than seven years, and all had severe pulmonary vascular obstructive disease; three have died. Thus, 14 of the 23 have died, and all but one surviving patient have mild to moderate disability. The generally grave prognosis for patients with truncus arteriosus warrants continued use of corrective operation, but suggests that the greatest benefit can be realized by successful correction in the infant with congestive heart failure and in early childhood before the development of severe pulmonary vascular obstructive disease.", "contents": "The natural history of truncus arteriosus. The cases of 23 patients whose condition was diagnosed as truncus arteriosus, type I or II, and who were seen at the Mayo Clinic during the decade preceding 1967, that is, before corrective operation became feasible, were reviewed. Ten were infants (through one year of age), and all ten have died. Eight ranged in age from more than one year through seven years of age, and all are living, except one, who diet 11 years after diagnosis. Five were older than seven years, and all had severe pulmonary vascular obstructive disease; three have died. Thus, 14 of the 23 have died, and all but one surviving patient have mild to moderate disability. The generally grave prognosis for patients with truncus arteriosus warrants continued use of corrective operation, but suggests that the greatest benefit can be realized by successful correction in the infant with congestive heart failure and in early childhood before the development of severe pulmonary vascular obstructive disease."} {"id": "PMID:1277413", "title": "The surgical management of discrete and diffuse supravalvar aortic stenosis.", "content": "Between 1956 and 1976, 18 patients underwent surgery for supravar aortic stenosis at the The Children's Hospital Medical Center, Boston. Discrete obstruction, present in 11, was treated by insertion of a prosthetic gusset placed across the area of narrowing and extending into the noncoronary sinus of Valsalva. There was one operative death. Residual gradients (measured in five patients) ranged from 4-55 mm Hg, one of which was supravalvar in location. Significant aortic regurgitation was not common preoperatively. The diffuse form of supravalvar obstruction, a more difficult surgical problem, was present in seven patients. There were three operative deaths. Complete relief of the pressure gradient was achieved only in one instance by insertion of a left ventricular-aortic bypass shunt diverting the majority of the cardiac output into the descending thoracic aorta. This patient is now asymptomatic 20 months following operation. On the basis of this experience, it is suggested that patients with the diffuse form of supravalvar obstruction, and perhaps even those with a hypoplastic annulus alone, would benefit from a left ventricular-aortic bypass shunt.", "contents": "The surgical management of discrete and diffuse supravalvar aortic stenosis. Between 1956 and 1976, 18 patients underwent surgery for supravar aortic stenosis at the The Children's Hospital Medical Center, Boston. Discrete obstruction, present in 11, was treated by insertion of a prosthetic gusset placed across the area of narrowing and extending into the noncoronary sinus of Valsalva. There was one operative death. Residual gradients (measured in five patients) ranged from 4-55 mm Hg, one of which was supravalvar in location. Significant aortic regurgitation was not common preoperatively. The diffuse form of supravalvar obstruction, a more difficult surgical problem, was present in seven patients. There were three operative deaths. Complete relief of the pressure gradient was achieved only in one instance by insertion of a left ventricular-aortic bypass shunt diverting the majority of the cardiac output into the descending thoracic aorta. This patient is now asymptomatic 20 months following operation. On the basis of this experience, it is suggested that patients with the diffuse form of supravalvar obstruction, and perhaps even those with a hypoplastic annulus alone, would benefit from a left ventricular-aortic bypass shunt."} {"id": "PMID:1277414", "title": "Transatrial resection of the obstructed right ventricular infundibulum.", "content": "Obstructions of the right ventricular infundibulum were resected through the orifice of the tricuspid valve in 21 patients, 15 of whom had tetralogy of Fallot. At operation the systolic pressure difference between the right ventricle and pulmonary artery after repair averaged 18 mm Hg (range 0-40 mm Hg). In patients with tetralogy, cardiac index four hours after operation averaged 2.8 L/M2/min. One patient with tetralogy and severe pulmonary hypertension died. Twelve patients with tetralogy were recatheterized 10 to 186 days after operation. The mean systolic pressure difference between right ventricle and pulmonary artery was 23 mm Hg. Residual obstructions were in the pulmonary valvular annulus. Cineangiograms did not show paradoxical motion of the right ventricular wall. Transatrial resection of right ventricular infundibular obstructions carries with it none of the consequences that often follow right ventriculotomy and this surgical approach satisfactorily relieves infundibular obstructions.", "contents": "Transatrial resection of the obstructed right ventricular infundibulum. Obstructions of the right ventricular infundibulum were resected through the orifice of the tricuspid valve in 21 patients, 15 of whom had tetralogy of Fallot. At operation the systolic pressure difference between the right ventricle and pulmonary artery after repair averaged 18 mm Hg (range 0-40 mm Hg). In patients with tetralogy, cardiac index four hours after operation averaged 2.8 L/M2/min. One patient with tetralogy and severe pulmonary hypertension died. Twelve patients with tetralogy were recatheterized 10 to 186 days after operation. The mean systolic pressure difference between right ventricle and pulmonary artery was 23 mm Hg. Residual obstructions were in the pulmonary valvular annulus. Cineangiograms did not show paradoxical motion of the right ventricular wall. Transatrial resection of right ventricular infundibular obstructions carries with it none of the consequences that often follow right ventriculotomy and this surgical approach satisfactorily relieves infundibular obstructions."} {"id": "PMID:1277415", "title": "Intracardiac repair of cardiac malformations with atrioventricular discordance.", "content": "Twenty-six patients with atrioventricular discordance and a variety of ventriculo-arterial connections have had appropriate intracardiac repairs. Seven of 26 patients (26.9%) died early postoperatively, but only two (11.1%) of 18 patients operated upon since May 1972 have died. Ten patients (40%) developed permanent complete heart block. Two patients died late postoperatively; 16 (84.1% of those surviving the early postoperative period) were in NYHA Class I or II at late follow-up. Seventeen of the patients had \"corrected transposition.\" Six developed tricuspid incompetence with regurgitation into the left atrium after repair. Two patients with atrioventricular discordance and double outlet right ventricle survived operation and are asymptomatic but have permanent pacemakers. One patient died after repair of double outlet left ventricle with atrioventricular discordance. Three of four patients with atrioventricular discordance and \"pseudotruncus arteriosus\" survived repair with valved external conduits and are well. One of two patients is well after repair of \"isolated ventricular inversion\" and ventricular septal defect.", "contents": "Intracardiac repair of cardiac malformations with atrioventricular discordance. Twenty-six patients with atrioventricular discordance and a variety of ventriculo-arterial connections have had appropriate intracardiac repairs. Seven of 26 patients (26.9%) died early postoperatively, but only two (11.1%) of 18 patients operated upon since May 1972 have died. Ten patients (40%) developed permanent complete heart block. Two patients died late postoperatively; 16 (84.1% of those surviving the early postoperative period) were in NYHA Class I or II at late follow-up. Seventeen of the patients had \"corrected transposition.\" Six developed tricuspid incompetence with regurgitation into the left atrium after repair. Two patients with atrioventricular discordance and double outlet right ventricle survived operation and are asymptomatic but have permanent pacemakers. One patient died after repair of double outlet left ventricle with atrioventricular discordance. Three of four patients with atrioventricular discordance and \"pseudotruncus arteriosus\" survived repair with valved external conduits and are well. One of two patients is well after repair of \"isolated ventricular inversion\" and ventricular septal defect."} {"id": "PMID:1277416", "title": "Failure of demand pacing with small surface area electrodes.", "content": "As pacemaker electrode myocardial contact area is reduced, the energy required to stimulate the heart decreases; but the effect of surface area on an electrode's ability to transmit R-wave potentials has not been well documented. Endocardial and intramyocardial R-wave potentials were measured in ten dogs with seven commercially available pacemaker electrodes of different surface area. With a load impedance of 1000 ohms, there was a direct correlation between surface area and the R-wave potentials measured. The amplitude of the R-wave that resulted from conduction from the heart to the sensor via the electrode system decreased with decreasing surface area. A similar direct correlation was seen between the R-wave potentials measured and the threshold current and energy requirements. With the present trend toward utilization of small surface area electrodes to reduce pacemaker cell drain, care must be taken to optimize pacemaker circuit impedance if sensing problems are to be avoided.", "contents": "Failure of demand pacing with small surface area electrodes. As pacemaker electrode myocardial contact area is reduced, the energy required to stimulate the heart decreases; but the effect of surface area on an electrode's ability to transmit R-wave potentials has not been well documented. Endocardial and intramyocardial R-wave potentials were measured in ten dogs with seven commercially available pacemaker electrodes of different surface area. With a load impedance of 1000 ohms, there was a direct correlation between surface area and the R-wave potentials measured. The amplitude of the R-wave that resulted from conduction from the heart to the sensor via the electrode system decreased with decreasing surface area. A similar direct correlation was seen between the R-wave potentials measured and the threshold current and energy requirements. With the present trend toward utilization of small surface area electrodes to reduce pacemaker cell drain, care must be taken to optimize pacemaker circuit impedance if sensing problems are to be avoided."} {"id": "PMID:1277417", "title": "Effects of perhexiline maleate on coronary flow distribution in the ischemic canine myocardium.", "content": "Intravenous perhexiline maleate in a canine preparation with fixed coronary flow increases coronary diastolic pressure. It also redistributes coronary flow so as to preserve endocardial flow. Myocardial oxygen consumption was reduced and lactate uptake enhanced by the drug. It had no effect upon the threshold for ischemic-induced left ventricular failure.", "contents": "Effects of perhexiline maleate on coronary flow distribution in the ischemic canine myocardium. Intravenous perhexiline maleate in a canine preparation with fixed coronary flow increases coronary diastolic pressure. It also redistributes coronary flow so as to preserve endocardial flow. Myocardial oxygen consumption was reduced and lactate uptake enhanced by the drug. It had no effect upon the threshold for ischemic-induced left ventricular failure."} {"id": "PMID:1277418", "title": "Valve ring abscess in active infective endocarditis. Frequency, location, and clues to clinical diagnosis from the study of 95 necropsy patients.", "content": "Analysis of 95 necropsy patients with active infective endocarditis (AIE) involving 128 native cardiac valves (aortic = 59, mitral = 48, tricuspid = 20, and pulmomic = 1) disclosed 27 patients with ring abscesses involving 30 valves: the aortic valve ring was infected in 24 patients and only an atrioventricular valve ring (mitral in two, and tricuspid in one) in three patients. Comparison of the following parameters showed no significant differences between the 27 patients with and the 68 patients without ring abscess: age, sex, antibiotic treatment or length of treatment, status of the cardiac valve(s) before infection, and the kind of infecting organism. Comparison of the following parameters, however, showed significant (P less than 0.05) differences between the 27 patients with and the 68 patients without valve ring abscess: 1) infection of the aortic valve; 2) occurrence of valvular regurgitation of recent origin; 3) presence of pericarditis; 4) presence of high degree of atrioventricular block; and 5) short duration of symptoms leading to severe debility or death. These five features, therefore, serve as a clinical clues to the presence of valve ring abscess in patients with AIE.", "contents": "Valve ring abscess in active infective endocarditis. Frequency, location, and clues to clinical diagnosis from the study of 95 necropsy patients. Analysis of 95 necropsy patients with active infective endocarditis (AIE) involving 128 native cardiac valves (aortic = 59, mitral = 48, tricuspid = 20, and pulmomic = 1) disclosed 27 patients with ring abscesses involving 30 valves: the aortic valve ring was infected in 24 patients and only an atrioventricular valve ring (mitral in two, and tricuspid in one) in three patients. Comparison of the following parameters showed no significant differences between the 27 patients with and the 68 patients without ring abscess: age, sex, antibiotic treatment or length of treatment, status of the cardiac valve(s) before infection, and the kind of infecting organism. Comparison of the following parameters, however, showed significant (P less than 0.05) differences between the 27 patients with and the 68 patients without valve ring abscess: 1) infection of the aortic valve; 2) occurrence of valvular regurgitation of recent origin; 3) presence of pericarditis; 4) presence of high degree of atrioventricular block; and 5) short duration of symptoms leading to severe debility or death. These five features, therefore, serve as a clinical clues to the presence of valve ring abscess in patients with AIE."} {"id": "PMID:1277426", "title": "The cortisol response during heart-lung bypass.", "content": "The response patterns of plasma cortisol and plasma free cortisol have been studied in 20 consecutive patients undergoing cardiac surgery involving the use of heart-lung bypass. Sixteen consecutive patients undergoing closed mitral valvotomy have been used as controls. Total plasma cortisol levels fell at the onset of extracorporeal circulation (ECC) and did not rise significantly throughout the period of ECC. The peak cortisol level in the bypass patients occurred at 24 hours postoperatively with elevated levels still present at 48 hours. This pattern was significantly different from the control patients (P less than 0.001) who exhibited the typical cortisol stress response pattern. Synthetic ACTH stimulation of the adrenal cortex during heart-lung bypass produced a positive response (i.e., a rise in plasma cortisol greater than 7.5 mug/100 ml) in all six patients studied while the six mitral valvotomy patients had no response to synthetic ACTH administration during operation (P less than 0.01). Plasma free cortisol estimations indicate that a rapid and significant rise in % free cortisol occurred at the onset of ECC, but that despite the rise in percentage free, the overall plasma free cortisol concentration (i.e., total plasma cortisol X % free) was significantly lower during ECC in the bypass patients when compared with control (P less than 0.01). Twenty-four hours postoperatively these concentrations were significantly higher in the bypass patients (P less than 0.001).", "contents": "The cortisol response during heart-lung bypass. The response patterns of plasma cortisol and plasma free cortisol have been studied in 20 consecutive patients undergoing cardiac surgery involving the use of heart-lung bypass. Sixteen consecutive patients undergoing closed mitral valvotomy have been used as controls. Total plasma cortisol levels fell at the onset of extracorporeal circulation (ECC) and did not rise significantly throughout the period of ECC. The peak cortisol level in the bypass patients occurred at 24 hours postoperatively with elevated levels still present at 48 hours. This pattern was significantly different from the control patients (P less than 0.001) who exhibited the typical cortisol stress response pattern. Synthetic ACTH stimulation of the adrenal cortex during heart-lung bypass produced a positive response (i.e., a rise in plasma cortisol greater than 7.5 mug/100 ml) in all six patients studied while the six mitral valvotomy patients had no response to synthetic ACTH administration during operation (P less than 0.01). Plasma free cortisol estimations indicate that a rapid and significant rise in % free cortisol occurred at the onset of ECC, but that despite the rise in percentage free, the overall plasma free cortisol concentration (i.e., total plasma cortisol X % free) was significantly lower during ECC in the bypass patients when compared with control (P less than 0.01). Twenty-four hours postoperatively these concentrations were significantly higher in the bypass patients (P less than 0.001)."} {"id": "PMID:1277427", "title": "Effect of hypertonic mannitol and isoproterenol on regional coronary flow following right ventriculotomy.", "content": "We studied the changes which occurred in regional coronary blood flow after right ventriculotomy and the subsequent effects of hypertonic mannitol or isoproterenol infusion. Regional coronary flows were measured with radioactive microspheres (9 micron) in open-chest anesthetized dogs. Either hypertonic mannitol (25%) was infused at 3.2 ml/min or 7.6 ml/min for 30 minutes, or normal saline at 7.6 ml/min for 30 minutes followed by isoproterenol at 0.05-0.10 mug/kg/min. In the mannitol treated animals right ventricular, left artrial and aortic pressures, heart rate, and cardiac output did not change significantly following vertical ventriculotomy, whereas in the saline-isoproterenol treated animals aortic pressures fell significantly. Coronary flow to the peri-incisional area fell from 41 to 24 ml/min-100 g (P less than 0.05) following ventriculotomy, increased by 34% (P less than 0.05) when osmolality rose after mannitol by 37 mOsm, but was unchanged with isoproterenol. The data indicate that a vertical ventriculotomy reduces flow to adjacent myocardium and that subsequent infusion of hypertonic mannitol at moderate rates significantly increases coronary flow to this region.", "contents": "Effect of hypertonic mannitol and isoproterenol on regional coronary flow following right ventriculotomy. We studied the changes which occurred in regional coronary blood flow after right ventriculotomy and the subsequent effects of hypertonic mannitol or isoproterenol infusion. Regional coronary flows were measured with radioactive microspheres (9 micron) in open-chest anesthetized dogs. Either hypertonic mannitol (25%) was infused at 3.2 ml/min or 7.6 ml/min for 30 minutes, or normal saline at 7.6 ml/min for 30 minutes followed by isoproterenol at 0.05-0.10 mug/kg/min. In the mannitol treated animals right ventricular, left artrial and aortic pressures, heart rate, and cardiac output did not change significantly following vertical ventriculotomy, whereas in the saline-isoproterenol treated animals aortic pressures fell significantly. Coronary flow to the peri-incisional area fell from 41 to 24 ml/min-100 g (P less than 0.05) following ventriculotomy, increased by 34% (P less than 0.05) when osmolality rose after mannitol by 37 mOsm, but was unchanged with isoproterenol. The data indicate that a vertical ventriculotomy reduces flow to adjacent myocardium and that subsequent infusion of hypertonic mannitol at moderate rates significantly increases coronary flow to this region."} {"id": "PMID:1277428", "title": "The protective effect of glucose-insulin-potassium on the response to atrial pacing.", "content": "The effects of glucose-insulin-potassium infusion (GIK) on atrial pacing-induced angina, ST depression, abnormal left ventricular end-diastolic pressure during pacing interruption (LVEDPi) and lactate metabolism (L), were studied in 18 patients: ten had angina during pacing = Ischemic group, and eight (5 normals and 3 with coronary artery disease) remained asymptomatic = Nonischemic group. The study consisted of 8-10 minute periods of control, pacing and recovery, before and after GIK. No untoward effects were observed. Comparison of the pacing responses (GIK vs pre-GIK states) showed that during GIK, angina occurred in only 4 patients, while significantly less severe changes were observed in ST depression (1.4 +/-0.5 vs 2.4 +/- 0.4 mm) and LVEDPi (16 +/- 3 vs 23 +/- 3 mm Hg). Lactate extraction was also higher (8.1 +/- 10.9 vs -5.2 +/- 11.1%), but not significantly so, although L became normal in 4 subjects and improved in another. These results indicate that GIK infusion was well tolerated and had a beneficial effect on pacing-induced myocardial ischemia.", "contents": "The protective effect of glucose-insulin-potassium on the response to atrial pacing. The effects of glucose-insulin-potassium infusion (GIK) on atrial pacing-induced angina, ST depression, abnormal left ventricular end-diastolic pressure during pacing interruption (LVEDPi) and lactate metabolism (L), were studied in 18 patients: ten had angina during pacing = Ischemic group, and eight (5 normals and 3 with coronary artery disease) remained asymptomatic = Nonischemic group. The study consisted of 8-10 minute periods of control, pacing and recovery, before and after GIK. No untoward effects were observed. Comparison of the pacing responses (GIK vs pre-GIK states) showed that during GIK, angina occurred in only 4 patients, while significantly less severe changes were observed in ST depression (1.4 +/-0.5 vs 2.4 +/- 0.4 mm) and LVEDPi (16 +/- 3 vs 23 +/- 3 mm Hg). Lactate extraction was also higher (8.1 +/- 10.9 vs -5.2 +/- 11.1%), but not significantly so, although L became normal in 4 subjects and improved in another. These results indicate that GIK infusion was well tolerated and had a beneficial effect on pacing-induced myocardial ischemia."} {"id": "PMID:1277429", "title": "A study of comparative blood pressure measures in predicting risk of coronary heart disease.", "content": "The Western Collaborative Group Study is a prospective study of 3,154 employed men, aged 39-59 years. Coronary heart disease (CHD) occurred in 257 subjects during 8.5 years of follow-up. The multiple logistic risk model was used to assess the comparative strength of systolic, diastolic, mean arterial and pulse pressure for the prediction of CHD in two age decades after adjustment for age, serum cholesterol, cigarette smoking, behavior pattern and weight. The risk of CHD was more strongly associated with the systolic than the diastolic pressure. The general practice of assessing the importance of blood pressure based only on the diastolic component should be reassessed.", "contents": "A study of comparative blood pressure measures in predicting risk of coronary heart disease. The Western Collaborative Group Study is a prospective study of 3,154 employed men, aged 39-59 years. Coronary heart disease (CHD) occurred in 257 subjects during 8.5 years of follow-up. The multiple logistic risk model was used to assess the comparative strength of systolic, diastolic, mean arterial and pulse pressure for the prediction of CHD in two age decades after adjustment for age, serum cholesterol, cigarette smoking, behavior pattern and weight. The risk of CHD was more strongly associated with the systolic than the diastolic pressure. The general practice of assessing the importance of blood pressure based only on the diastolic component should be reassessed."} {"id": "PMID:1277430", "title": "The early posthospital phase of myocardial infarction. Prognostic stratification.", "content": "Prognostic stratification was carried out on 518 patients less than or equal to 65 years of age who were discharged from the hospital following a definite or probable acute myocardial infarction and followed for four months. The total population was made up of 272 patients hospitalzed in 1973 and 246 patients hospitalized in 1974; one hundred and forty-two variables were collected on each patient. The clinical characteristics of the 1973 and 1974 populations were remarkably similar, and both groups had a four-month posthospital cardiac mortality rate of 4%. Two prognostic stratification schemes were developed on the 1973 population which identified low and high risk groups with meaningfully different four-month cardiac death rates. Both stratification schemes were tested on the 1974 population, and one of the two schemes was validated as identifying a significantly increased cardiac mortality rate in the high as opposed to the low risk group. The four-month posthospital cardiac mortality rate was 3% in the low and 14% in the high risk group (Z = 2.70, P less than 0.003). The high risk group was characterized by two or more of the following characteristics: 1) history of angina at ordinary levels of activity or at rest; 2) CCU hypotension and/or congestive heart failure; 3) ventricular premature beat frequency greater than or equal to 20/hr on a six-hour electrocardiographic tape recording. The low risk group had none or only one of the above characteristcis. The prognostic power of this stratification scheme is such that sixteen percent of the posthospital population can be identified as high risk, and this subgroup contains forty-six percent of the patients who die of cardiac cause in the four-month posthospital interval.", "contents": "The early posthospital phase of myocardial infarction. Prognostic stratification. Prognostic stratification was carried out on 518 patients less than or equal to 65 years of age who were discharged from the hospital following a definite or probable acute myocardial infarction and followed for four months. The total population was made up of 272 patients hospitalzed in 1973 and 246 patients hospitalized in 1974; one hundred and forty-two variables were collected on each patient. The clinical characteristics of the 1973 and 1974 populations were remarkably similar, and both groups had a four-month posthospital cardiac mortality rate of 4%. Two prognostic stratification schemes were developed on the 1973 population which identified low and high risk groups with meaningfully different four-month cardiac death rates. Both stratification schemes were tested on the 1974 population, and one of the two schemes was validated as identifying a significantly increased cardiac mortality rate in the high as opposed to the low risk group. The four-month posthospital cardiac mortality rate was 3% in the low and 14% in the high risk group (Z = 2.70, P less than 0.003). The high risk group was characterized by two or more of the following characteristics: 1) history of angina at ordinary levels of activity or at rest; 2) CCU hypotension and/or congestive heart failure; 3) ventricular premature beat frequency greater than or equal to 20/hr on a six-hour electrocardiographic tape recording. The low risk group had none or only one of the above characteristcis. The prognostic power of this stratification scheme is such that sixteen percent of the posthospital population can be identified as high risk, and this subgroup contains forty-six percent of the patients who die of cardiac cause in the four-month posthospital interval."} {"id": "PMID:1277431", "title": "Functional significance of regional ischemic contraction abnormalities.", "content": "To evaluate the progression of segment function following induction of ischemia, the left anterior descending coronary artery was ligated (eight dogs) or cannulated and perfused at various pressures via a bypass-oxygenator (six dogs). Mercury-in-silastic length gauges were sutured to the anterior left ventricle, and pressure was recorded by a catheter-tipped transducer. Segment function was determined from the area of the pressure-length loop by plotting instantaneous left ventricular pressure against segment length and by evaluation of the degree of systolic shortening. Segment function decreased linearly as flow in the left anterior descending artery was decreased in a stepwise fashion by reduction in perfusion pressures from 100 to 20 mm Hg. With both left anterior descending coronary artery ligation and stepwise flow reduction, the pressure-length loop invariably showed four clearly identifiable morphologic patterns which relate conceptually to the specific left ventricular contraction patterns: dyssynchrony, hypokinesis, akinesis, and paradoxic systolic expansion. Re-oxygenation following occlusion invariably revealed return to a normal pattern in reverse order. This study demonstrates that a consistent and predictable progression of segmental contraction abnormalities occurs with ischemia.", "contents": "Functional significance of regional ischemic contraction abnormalities. To evaluate the progression of segment function following induction of ischemia, the left anterior descending coronary artery was ligated (eight dogs) or cannulated and perfused at various pressures via a bypass-oxygenator (six dogs). Mercury-in-silastic length gauges were sutured to the anterior left ventricle, and pressure was recorded by a catheter-tipped transducer. Segment function was determined from the area of the pressure-length loop by plotting instantaneous left ventricular pressure against segment length and by evaluation of the degree of systolic shortening. Segment function decreased linearly as flow in the left anterior descending artery was decreased in a stepwise fashion by reduction in perfusion pressures from 100 to 20 mm Hg. With both left anterior descending coronary artery ligation and stepwise flow reduction, the pressure-length loop invariably showed four clearly identifiable morphologic patterns which relate conceptually to the specific left ventricular contraction patterns: dyssynchrony, hypokinesis, akinesis, and paradoxic systolic expansion. Re-oxygenation following occlusion invariably revealed return to a normal pattern in reverse order. This study demonstrates that a consistent and predictable progression of segmental contraction abnormalities occurs with ischemia."} {"id": "PMID:1277432", "title": "Echocardiographic assessment of left-to-right shunt volume in children with ventricular septal defect.", "content": "Echocardiograms were performed in 20 infants and children with isolated ventricular septal defects (VSD) undergoing cardiac catheterization. The magnitude of the left-to-right shunt was expressed as the pulmonary-to-systemic flow ratio (Qp/Os) and was compared to a ratio of the echographic left atrial (LA) diameter to the aortic root (Ao) diameter (LA/Ao). The Qp/Qs was also compared to LA/m2. Thirty-three normal children served as controls. The LA/m2 and Ao/m2 were significantly larger in normal infants under one year of age than in children above one year. The LA/Ao, however, was not influenced by age or size. A strong linear relationship was found between Qp/Qs and the LA/Ao (r = 0.96). The LA/Ao measurement appears to be helpful in the noninvasive assessment of the left-to-right shunt in patients with VSD.", "contents": "Echocardiographic assessment of left-to-right shunt volume in children with ventricular septal defect. Echocardiograms were performed in 20 infants and children with isolated ventricular septal defects (VSD) undergoing cardiac catheterization. The magnitude of the left-to-right shunt was expressed as the pulmonary-to-systemic flow ratio (Qp/Os) and was compared to a ratio of the echographic left atrial (LA) diameter to the aortic root (Ao) diameter (LA/Ao). The Qp/Qs was also compared to LA/m2. Thirty-three normal children served as controls. The LA/m2 and Ao/m2 were significantly larger in normal infants under one year of age than in children above one year. The LA/Ao, however, was not influenced by age or size. A strong linear relationship was found between Qp/Qs and the LA/Ao (r = 0.96). The LA/Ao measurement appears to be helpful in the noninvasive assessment of the left-to-right shunt in patients with VSD."} {"id": "PMID:1277433", "title": "Determinants of ventricular septal motion. Influence of relative right and left ventricular size.", "content": "To test the hypothesis that the ventricular septum moves during systole toward the center of the ventricular mass (so that the end-diastolic position of the septum within the heart should determine both the direction and the magnitude of septal motion during systole), echocardiograms from patients with several different hemodynamic burdens were analyzed. A linear relation was noted between the end-diastolic intracardiac position of the ventricular septum and the direction and magnitude of systolic septal motion in 1) forty three patients with an atrial septal defect )regression coefficient r = 0.80), 2) fourteen patients with other causes of right ventricular volume overload (r = 0.82), 3) nineteen patients with left ventricular volume overload (r = 0.74), 4) ten patients with right ventricular pressure overload (r = 0.93), 5) ten patients with left ventricular pressure overload (r = 0.80), 6) twenty-eight normal subjects (r = 0.82). We conclude that, in the presence of normal ventricular activation and contraction, the direction and magnitude of sepatal motion during systole is determined by the intracardiac position of the septum at enddiastole.", "contents": "Determinants of ventricular septal motion. Influence of relative right and left ventricular size. To test the hypothesis that the ventricular septum moves during systole toward the center of the ventricular mass (so that the end-diastolic position of the septum within the heart should determine both the direction and the magnitude of septal motion during systole), echocardiograms from patients with several different hemodynamic burdens were analyzed. A linear relation was noted between the end-diastolic intracardiac position of the ventricular septum and the direction and magnitude of systolic septal motion in 1) forty three patients with an atrial septal defect )regression coefficient r = 0.80), 2) fourteen patients with other causes of right ventricular volume overload (r = 0.82), 3) nineteen patients with left ventricular volume overload (r = 0.74), 4) ten patients with right ventricular pressure overload (r = 0.93), 5) ten patients with left ventricular pressure overload (r = 0.80), 6) twenty-eight normal subjects (r = 0.82). We conclude that, in the presence of normal ventricular activation and contraction, the direction and magnitude of sepatal motion during systole is determined by the intracardiac position of the septum at enddiastole."} {"id": "PMID:1277434", "title": "Echocardiographic evaluation of the stent mounted aortic bioprosthetic valve in the mitral position. In vitro and in vivo studies.", "content": "Echocardiograms were performed on 20 clinically stable patients following mitral valve replacement with glutaraldehyde-preserved porcine aortic heterografts and three patients with antibiotic sterilized aortic homografts mounted in the mitral position. Such valves were evaluated in a test chamber at varied flow rates resulting in improved understanding of movements seen with the echocardiogram in vivo. The technique for recording the valvular stent and leaflets is described and a method for measuring several parameters is demonstrated. Initial diastolic slope averaged 2.4 +/- 0.5 cm/sec (range 1.9 to 3.3 cm/sec). Left ventricular outflow tract measured from the anterior portion of the stent to the interventricular septum averaged 1.5 +/- 0.5 cm at end-diastole and 1.3 +/- 0.6 cm at end-systole. Leaflet excursion averaged 1.5 +/- 0.3 cm (with a range from 1.0 to 2.1 cm). The ratio of internal to external stent diameters averaged 0.66 +/- 0.05 (with a range from 0.56 to 0.74).", "contents": "Echocardiographic evaluation of the stent mounted aortic bioprosthetic valve in the mitral position. In vitro and in vivo studies. Echocardiograms were performed on 20 clinically stable patients following mitral valve replacement with glutaraldehyde-preserved porcine aortic heterografts and three patients with antibiotic sterilized aortic homografts mounted in the mitral position. Such valves were evaluated in a test chamber at varied flow rates resulting in improved understanding of movements seen with the echocardiogram in vivo. The technique for recording the valvular stent and leaflets is described and a method for measuring several parameters is demonstrated. Initial diastolic slope averaged 2.4 +/- 0.5 cm/sec (range 1.9 to 3.3 cm/sec). Left ventricular outflow tract measured from the anterior portion of the stent to the interventricular septum averaged 1.5 +/- 0.5 cm at end-diastole and 1.3 +/- 0.6 cm at end-systole. Leaflet excursion averaged 1.5 +/- 0.3 cm (with a range from 1.0 to 2.1 cm). The ratio of internal to external stent diameters averaged 0.66 +/- 0.05 (with a range from 0.56 to 0.74)."} {"id": "PMID:1277435", "title": "Asthma due to inhaled chemical agents--amprolium hydrochloride.", "content": "A man with no previous history of allergy or chest disease developed asthma after exposure to a heavy atmospheric concentration of amprolium hydrochloride which is a constituent of a poultry-food additive. Subsequent experimental exposure produced an immediate asthmatic reaction which was inhibited by sodium cromoglycate.", "contents": "Asthma due to inhaled chemical agents--amprolium hydrochloride. A man with no previous history of allergy or chest disease developed asthma after exposure to a heavy atmospheric concentration of amprolium hydrochloride which is a constituent of a poultry-food additive. Subsequent experimental exposure produced an immediate asthmatic reaction which was inhibited by sodium cromoglycate."} {"id": "PMID:1277436", "title": "Investigation of a respiratory disease associated with an air-conditioning system.", "content": "This paper describes the investigation of respiratory disease presenting in a group of men employed on the printing floor of a factory. The air-conditioning units supplying this floor were found to be contaminated with a variety of micro-organisms. The specific cause of the disease was not identified but an alteration in the system of humidification led to the complete resolution of symptoms.", "contents": "Investigation of a respiratory disease associated with an air-conditioning system. This paper describes the investigation of respiratory disease presenting in a group of men employed on the printing floor of a factory. The air-conditioning units supplying this floor were found to be contaminated with a variety of micro-organisms. The specific cause of the disease was not identified but an alteration in the system of humidification led to the complete resolution of symptoms."} {"id": "PMID:1277437", "title": "Hypersensitivity to acetylsalicylic acid (ASA) and tartrazine in patients with asthma.", "content": "One-hundred and forty asthmatics were tested perorally with acetylsalicylic acid (ASA), and/or with the azo-colour tartrazine; a fall in PEF of more than 20% was accepted as a positive result. About one quarter of the patients displayed a positive reaction to one of the two tested agents. No significant correlation was found between the reactions of these, and the presence of atopy, nasal polyposis, sinusitis, rhinitis, sensitivity to cold air, the age at onset, duration of asthma, or history of sensitivity to alcoholic drinks. The history suggested sensitivity to ingested, possibly coloured, food and drink, in only about one third of the tartrazine-positive cases. The ASA provocation tests were mainly applied to patients with doubtful or negative histories of sensitivity to ASA-containing drugs. The frequency of cross-reactivity between the two tested agents was statistically significant; patients reacting to tartrazine were for the most part, also sensitive to ASA. Tests for sensitivity to analgesics and food additives should be conducted as a routine measure in asthmatics, and sensitive patients should be given information on suitable medication and dietary control.", "contents": "Hypersensitivity to acetylsalicylic acid (ASA) and tartrazine in patients with asthma. One-hundred and forty asthmatics were tested perorally with acetylsalicylic acid (ASA), and/or with the azo-colour tartrazine; a fall in PEF of more than 20% was accepted as a positive result. About one quarter of the patients displayed a positive reaction to one of the two tested agents. No significant correlation was found between the reactions of these, and the presence of atopy, nasal polyposis, sinusitis, rhinitis, sensitivity to cold air, the age at onset, duration of asthma, or history of sensitivity to alcoholic drinks. The history suggested sensitivity to ingested, possibly coloured, food and drink, in only about one third of the tartrazine-positive cases. The ASA provocation tests were mainly applied to patients with doubtful or negative histories of sensitivity to ASA-containing drugs. The frequency of cross-reactivity between the two tested agents was statistically significant; patients reacting to tartrazine were for the most part, also sensitive to ASA. Tests for sensitivity to analgesics and food additives should be conducted as a routine measure in asthmatics, and sensitive patients should be given information on suitable medication and dietary control."} {"id": "PMID:1277438", "title": "IgE antibodies to house dust, mite, animal allergens and moulds in house dust hypersensitivity.", "content": "Fifty-three patients were investigated by intradermal tests and Phadebas RAST and, in most cases, the serum IgE level was determined. They were tested for sensitivity to house dust, Dermatophagoides pteronyssinus, cat, dog, horse and mould allergens. All cases with IgE antibodies to house dust were found to have specific IgE to other tested allergens as well. Eighty-nine per cent of the patients being RAST positive for house dust were also positive for D. pteronyssinus and in the majority of those cases IgE antibodies to other allergens were detected. The results reaffirm previous findings that the mite is not the only allergen in house dust and that extract of house dust is a mixture of several allergenic substances, which make it less suitable for differential testing. It is concluded that serum IgE determination is of value as a screening procedure in the diagnosis and that the use of a number of specific allergens in RAST is valuable in pinpointing the offending allergen in house dust hypersensitivity.", "contents": "IgE antibodies to house dust, mite, animal allergens and moulds in house dust hypersensitivity. Fifty-three patients were investigated by intradermal tests and Phadebas RAST and, in most cases, the serum IgE level was determined. They were tested for sensitivity to house dust, Dermatophagoides pteronyssinus, cat, dog, horse and mould allergens. All cases with IgE antibodies to house dust were found to have specific IgE to other tested allergens as well. Eighty-nine per cent of the patients being RAST positive for house dust were also positive for D. pteronyssinus and in the majority of those cases IgE antibodies to other allergens were detected. The results reaffirm previous findings that the mite is not the only allergen in house dust and that extract of house dust is a mixture of several allergenic substances, which make it less suitable for differential testing. It is concluded that serum IgE determination is of value as a screening procedure in the diagnosis and that the use of a number of specific allergens in RAST is valuable in pinpointing the offending allergen in house dust hypersensitivity."} {"id": "PMID:1277439", "title": "Pulmonary responses to particulate materials capable of activating the alternative pathway of complement.", "content": "The cellular sequence of events evoked by the intratracheal injection of both respirable mouldy hay dust and zymosan in unsensitized rats and rabbits was markedly similar and contained many features seen in lung biopsies from farmer's lung cases. It is considered that a combination of ability to activate the alternative pathway of complement and the particulate nature of mouldy hay dust and zymosan produced the pulmonary response seen and as such, considerable insight has been gained into mechanisms by which unsensitized individuals respond to dust inhalation. It is suggested that alternative pathway activation may produce an attack of farmer's lung in the absence of precipitins or other forms of hypersensitivity to the dust or its components and that cases designated as 'pulmonary mycotoxicosis' are more rationally explained by this mechanism.", "contents": "Pulmonary responses to particulate materials capable of activating the alternative pathway of complement. The cellular sequence of events evoked by the intratracheal injection of both respirable mouldy hay dust and zymosan in unsensitized rats and rabbits was markedly similar and contained many features seen in lung biopsies from farmer's lung cases. It is considered that a combination of ability to activate the alternative pathway of complement and the particulate nature of mouldy hay dust and zymosan produced the pulmonary response seen and as such, considerable insight has been gained into mechanisms by which unsensitized individuals respond to dust inhalation. It is suggested that alternative pathway activation may produce an attack of farmer's lung in the absence of precipitins or other forms of hypersensitivity to the dust or its components and that cases designated as 'pulmonary mycotoxicosis' are more rationally explained by this mechanism."} {"id": "PMID:1277440", "title": "Dependence of immediate hypersensitivity on the month of birth.", "content": "This report describes a retrospective study of 1421 patients allergic to pollens and 728 patients allergic to animal epithelia. In males, but not in females, the month-of-birth distribution differed significantly from that in the total population of Finland (P less than 0-01 in pollen allergy and P less than 0-05 in epithelium allergy). The phenomenon was most clearly apparent in boys aged 10-14 born in 1960-4 (P less than 0-01 in pollen allergy and P less than 0-001 in epithelium allergy). When the relative risk of immediate hypersensitivity was plotted as a function of the month of birth, a two-phasic curve with maxima in March-May and September-November was obtained for both pollen allergy and animal epithelium allergy. The results indicate that boys, but perhaps not girls, have a sensitive period early in life during which one or more environmental factor and seasonal variations in this factor influence the development of subsequent immediate hypersensitivity.", "contents": "Dependence of immediate hypersensitivity on the month of birth. This report describes a retrospective study of 1421 patients allergic to pollens and 728 patients allergic to animal epithelia. In males, but not in females, the month-of-birth distribution differed significantly from that in the total population of Finland (P less than 0-01 in pollen allergy and P less than 0-05 in epithelium allergy). The phenomenon was most clearly apparent in boys aged 10-14 born in 1960-4 (P less than 0-01 in pollen allergy and P less than 0-001 in epithelium allergy). When the relative risk of immediate hypersensitivity was plotted as a function of the month of birth, a two-phasic curve with maxima in March-May and September-November was obtained for both pollen allergy and animal epithelium allergy. The results indicate that boys, but perhaps not girls, have a sensitive period early in life during which one or more environmental factor and seasonal variations in this factor influence the development of subsequent immediate hypersensitivity."} {"id": "PMID:1277441", "title": "The diagnosis of aspirin idiosyncrasy by analgesic challenge.", "content": "Analgesic challenge was employed to identify fifty patients with aspirin idiosyncrasy. No serious reactions were observed using the method described. Patients with a history of the condition were highly sensitive and reacted to small doses of aspirin or to paracetamol. Patients with a positive challenge test, but previously unaware of aspirin idiosyncrasy, were less sensitive: they required larger challenge doses of aspirin and did not respond to paracetamol challenge. In the absence of an in vitro test, analgesic challenge is the only means of confirming the presence of aspirin idiosyncrasy.", "contents": "The diagnosis of aspirin idiosyncrasy by analgesic challenge. Analgesic challenge was employed to identify fifty patients with aspirin idiosyncrasy. No serious reactions were observed using the method described. Patients with a history of the condition were highly sensitive and reacted to small doses of aspirin or to paracetamol. Patients with a positive challenge test, but previously unaware of aspirin idiosyncrasy, were less sensitive: they required larger challenge doses of aspirin and did not respond to paracetamol challenge. In the absence of an in vitro test, analgesic challenge is the only means of confirming the presence of aspirin idiosyncrasy."} {"id": "PMID:1277442", "title": "Immediate (type I) allergic responses to platinum compounds.", "content": "A series of platinum complexes has been used for allergy tests in a number of platinum refinery workers who are known to be sensitive to hexachloroplatinate ([PtCl6]2-) salts. The results show that the allergy-eliciting compounds are confined to a very small group of ionic complexes containing reactive halogen ligands. Neutral complexes and those containing more strongly bound ligands are totally inactive. These variations in activity are interpreted in terms of established kinetic and thermodynamic parameters.", "contents": "Immediate (type I) allergic responses to platinum compounds. A series of platinum complexes has been used for allergy tests in a number of platinum refinery workers who are known to be sensitive to hexachloroplatinate ([PtCl6]2-) salts. The results show that the allergy-eliciting compounds are confined to a very small group of ionic complexes containing reactive halogen ligands. Neutral complexes and those containing more strongly bound ligands are totally inactive. These variations in activity are interpreted in terms of established kinetic and thermodynamic parameters."} {"id": "PMID:1277444", "title": "Curve prediction in automated analyses in routine laboratories.", "content": "1. The hydraulics of first- and second-generation AutoAnalyzers introduce lag and exponential deformations of the square wave signal expected from the colorimeter. These factors limit sampling rates by causing sample interaction. Curve regeneration carried out on Technicon Flame IV modules, using a digital approach, with a Hewlett-Packard 2100A computer, has successfully compensated for exponential deformation of sodium, potassium, chloride and carbon dioxide channels in routine laboratory use for one year. A sampling rate of 138/hr has been used; faster rates are possible. 2. Reduced sample and reagent consumption are benefits in addition to the increased analysis rate.", "contents": "Curve prediction in automated analyses in routine laboratories. 1. The hydraulics of first- and second-generation AutoAnalyzers introduce lag and exponential deformations of the square wave signal expected from the colorimeter. These factors limit sampling rates by causing sample interaction. Curve regeneration carried out on Technicon Flame IV modules, using a digital approach, with a Hewlett-Packard 2100A computer, has successfully compensated for exponential deformation of sodium, potassium, chloride and carbon dioxide channels in routine laboratory use for one year. A sampling rate of 138/hr has been used; faster rates are possible. 2. Reduced sample and reagent consumption are benefits in addition to the increased analysis rate."} {"id": "PMID:1277445", "title": "Intestinal absorption of water and electrolytes.", "content": "1. Recent advances in knowledge of intestinal physiology have provided some insight into disturbed mechanisms and their clinical effects; for example, diarrhoea can now be defined biochemically as excessive fluid and electrolyte loss due to their malabsorption or excessive secretion. 2. Because of differences in structure and in absorptive and secretory mechanisms, the various parts of the gut perform different functions. In the jejunum, transport activity is extensive and the rapid equilibration of its content provides the optimal absorptive mixture. Functionally, the ileum and colon are similar; compared with the jejunum, they have greater absorptive capacity for electrolytes and generate significantly higher transmural electrical potentials. In the colon, some transport mechanisms are potentiated by adrenocortical steroids. 3. Water and electrolyte absorption and secretion are the end-products of bidirectional fluxes across the intestinal wall that are several times greater than net movement in either direction. Secretion is the surplus of negative flux (into the lumen) and absorption the surplus of positive flux (out of it). 4. Many electrolyte transport mechanisms require the absorption of other electrolytes or non-electrolytes, and some are concerned with electrolyte exchange. Water transport is always passive, in the direction of solute flow, but its solvent drag can move solutes across the intestinal membrane.", "contents": "Intestinal absorption of water and electrolytes. 1. Recent advances in knowledge of intestinal physiology have provided some insight into disturbed mechanisms and their clinical effects; for example, diarrhoea can now be defined biochemically as excessive fluid and electrolyte loss due to their malabsorption or excessive secretion. 2. Because of differences in structure and in absorptive and secretory mechanisms, the various parts of the gut perform different functions. In the jejunum, transport activity is extensive and the rapid equilibration of its content provides the optimal absorptive mixture. Functionally, the ileum and colon are similar; compared with the jejunum, they have greater absorptive capacity for electrolytes and generate significantly higher transmural electrical potentials. In the colon, some transport mechanisms are potentiated by adrenocortical steroids. 3. Water and electrolyte absorption and secretion are the end-products of bidirectional fluxes across the intestinal wall that are several times greater than net movement in either direction. Secretion is the surplus of negative flux (into the lumen) and absorption the surplus of positive flux (out of it). 4. Many electrolyte transport mechanisms require the absorption of other electrolytes or non-electrolytes, and some are concerned with electrolyte exchange. Water transport is always passive, in the direction of solute flow, but its solvent drag can move solutes across the intestinal membrane."} {"id": "PMID:1277446", "title": "Diagnosis of chronic pancreatic disease.", "content": "The diagnosis of pancreatic disease is difficult. The first step is clinical suspicion, based on the symptoms and signs. If pancreatic disease is suspected, investigation is necessary to prove this diagnosis. Investigation aims to answer two questions: a) is there pancreatic disease and b) if so, what type? The first question may be answered by demonstrating abnormal pancreatic function, using pancreatic function tests, whereas the second is answered by using techniques to demonstrate structural (anatomical) abnormalities of the pancreas. a) The methods to establish abnormal pancreatic function consist of 1. tests to demonstrate abnormal digestive capability, 2. tests to study pancreatic exocrine secretion, and 3. tests to study endocrine secretion. The tests of group 1 are: chemical fat balance study before and during enzyme replacement therapy, faecal nitrogen balance study, and the demonstration of either the malabsorption of vitamins A, D and K or the sequelae of their malabsorption (low serum calcium, high alkaline phosphatase, prolonged prothrombin time, etc.). Abnormal vitamin B12 absorption also may be present. 2. The tests designed to study pancreatic exocrine secretion are determination of the presence or absence of proteolytic enzymes in the stool, the secretion test, the pancreozymin stimulation test and the Lundh test. The serum amylase and lipase values are of little help in assessment of pancreatic function. 3. The tests to study endocrine function are the glucose tolerances test (which frequently gives abnormal results in pancreatic disease), and radioimmunoassays for insulin and gastrointestinal hormones (which may be increased in patients with functioning tumours of the islet cells). b) The techniques used to establish structural abnormalities of the pancreas are: duodenal cytology (during secretin tests), radiological techniques (abdominal survey films, barium meal, hypotonic duodenography, roentgenography of the biliary tract, barium enema, and angiography,) gastroscopy, duodensocopy, endoscopy and retrograde pancreatography, echography, scan and laparotomy. The relative value of these tests is discussed.", "contents": "Diagnosis of chronic pancreatic disease. The diagnosis of pancreatic disease is difficult. The first step is clinical suspicion, based on the symptoms and signs. If pancreatic disease is suspected, investigation is necessary to prove this diagnosis. Investigation aims to answer two questions: a) is there pancreatic disease and b) if so, what type? The first question may be answered by demonstrating abnormal pancreatic function, using pancreatic function tests, whereas the second is answered by using techniques to demonstrate structural (anatomical) abnormalities of the pancreas. a) The methods to establish abnormal pancreatic function consist of 1. tests to demonstrate abnormal digestive capability, 2. tests to study pancreatic exocrine secretion, and 3. tests to study endocrine secretion. The tests of group 1 are: chemical fat balance study before and during enzyme replacement therapy, faecal nitrogen balance study, and the demonstration of either the malabsorption of vitamins A, D and K or the sequelae of their malabsorption (low serum calcium, high alkaline phosphatase, prolonged prothrombin time, etc.). Abnormal vitamin B12 absorption also may be present. 2. The tests designed to study pancreatic exocrine secretion are determination of the presence or absence of proteolytic enzymes in the stool, the secretion test, the pancreozymin stimulation test and the Lundh test. The serum amylase and lipase values are of little help in assessment of pancreatic function. 3. The tests to study endocrine function are the glucose tolerances test (which frequently gives abnormal results in pancreatic disease), and radioimmunoassays for insulin and gastrointestinal hormones (which may be increased in patients with functioning tumours of the islet cells). b) The techniques used to establish structural abnormalities of the pancreas are: duodenal cytology (during secretin tests), radiological techniques (abdominal survey films, barium meal, hypotonic duodenography, roentgenography of the biliary tract, barium enema, and angiography,) gastroscopy, duodensocopy, endoscopy and retrograde pancreatography, echography, scan and laparotomy. The relative value of these tests is discussed."} {"id": "PMID:1277447", "title": "Tests of intestinal function.", "content": "The most important tests for investigating the functions of the small bowel are faecal-fat analysis, the determination of xylose tolerance, vitamin-B12 absorption, and 14C-glycoholate transport, barium examination of the small bowel, and small bowel biopsy. With these tests, most disorders of digestion and of absorption can be adequately investigated and diagnosed.", "contents": "Tests of intestinal function. The most important tests for investigating the functions of the small bowel are faecal-fat analysis, the determination of xylose tolerance, vitamin-B12 absorption, and 14C-glycoholate transport, barium examination of the small bowel, and small bowel biopsy. With these tests, most disorders of digestion and of absorption can be adequately investigated and diagnosed."} {"id": "PMID:1277448", "title": "Xylose absorption and its clinical significance.", "content": "1. Xylose absorption by the small intestine probably includes an active process. 2. For xylose testing, the 25-g dose appears to be preferable to 5 g. 3. Factors that influence the test result include intestinal bacterial overgrowth, reduced xylose metabolism in cases of liver disease, sequestration into ascites, age, and the state of renal function. 4. The test results differentiate patients with extensive disease of the upper small intestine from normal subjects, and from patients with steatorrhoea due to pancreatic insufficiency, in most but not all instances. Blood xylose levels combined with urinary xylose output aids discrimination.", "contents": "Xylose absorption and its clinical significance. 1. Xylose absorption by the small intestine probably includes an active process. 2. For xylose testing, the 25-g dose appears to be preferable to 5 g. 3. Factors that influence the test result include intestinal bacterial overgrowth, reduced xylose metabolism in cases of liver disease, sequestration into ascites, age, and the state of renal function. 4. The test results differentiate patients with extensive disease of the upper small intestine from normal subjects, and from patients with steatorrhoea due to pancreatic insufficiency, in most but not all instances. Blood xylose levels combined with urinary xylose output aids discrimination."} {"id": "PMID:1277449", "title": "Bile-acid metabolism and the liver.", "content": "Primary bile acids are exclusively synthesize, and all bile acids are conjugated, in the liver. When hepatic function is altered by disease, not surprisingly the bile-acid metabolism reflects this change. 1. In chronic liver disorders the glycine: taurine ratio of serum and bile is reduced. 2. In cases of relapsing acute hepatitis and relapsing chronic active hepatitis the serum bile acids are increased, providing an aid to early diagnosis. Their pattern often distinguishes chronic cholestatic conditions from Laennec's cirrhosis. 3. In chronic liver disease, the concentration of intraduodenal bile acids is reduced; when the reduction is severe, this probably accounts for co-existent steatorrhoea. 4. In Laennec's cirrhosis, both the synthesis and pool size of cholic acid are markedly depressed; in primary biliary cirrhosis, however, preliminary data indicate a decrease in the chenodeoxycholic acid component.", "contents": "Bile-acid metabolism and the liver. Primary bile acids are exclusively synthesize, and all bile acids are conjugated, in the liver. When hepatic function is altered by disease, not surprisingly the bile-acid metabolism reflects this change. 1. In chronic liver disorders the glycine: taurine ratio of serum and bile is reduced. 2. In cases of relapsing acute hepatitis and relapsing chronic active hepatitis the serum bile acids are increased, providing an aid to early diagnosis. Their pattern often distinguishes chronic cholestatic conditions from Laennec's cirrhosis. 3. In chronic liver disease, the concentration of intraduodenal bile acids is reduced; when the reduction is severe, this probably accounts for co-existent steatorrhoea. 4. In Laennec's cirrhosis, both the synthesis and pool size of cholic acid are markedly depressed; in primary biliary cirrhosis, however, preliminary data indicate a decrease in the chenodeoxycholic acid component."} {"id": "PMID:1277450", "title": "How an enzyme works.", "content": "The structure of enzyme active sites and the nature of the catalytic process are reviewed. The impressive efficiency of these protein catalysts appears to stem from such factors as proximity and orientation of enzyme and substrate moieties, strain, and the occurrence of distinctive microenvironments within catalytic centres. Carboxypeptidase, lysozyme, and aspartate transcarbamylase, which have been extensively investigated by many techniques, serve to illustrate the application of these concepts.", "contents": "How an enzyme works. The structure of enzyme active sites and the nature of the catalytic process are reviewed. The impressive efficiency of these protein catalysts appears to stem from such factors as proximity and orientation of enzyme and substrate moieties, strain, and the occurrence of distinctive microenvironments within catalytic centres. Carboxypeptidase, lysozyme, and aspartate transcarbamylase, which have been extensively investigated by many techniques, serve to illustrate the application of these concepts."} {"id": "PMID:1277451", "title": "Errors in measuring enzyme activity by reaction-rate methods.", "content": "1. The two types of assay used in clinical enzymology -- reaction-rate and two-point assays -- are usually performed with different types of analyzers. A third type, the multi-point analyzer, has been introduced recently. 2. Reaction-rate and two-point enzyme assays have sources of error inherent in their methodologies. There are also major errors due to the analytical system itself; these are considered systematically.", "contents": "Errors in measuring enzyme activity by reaction-rate methods. 1. The two types of assay used in clinical enzymology -- reaction-rate and two-point assays -- are usually performed with different types of analyzers. A third type, the multi-point analyzer, has been introduced recently. 2. Reaction-rate and two-point enzyme assays have sources of error inherent in their methodologies. There are also major errors due to the analytical system itself; these are considered systematically."} {"id": "PMID:1277452", "title": "Demographic and analytic factors affecting the normal range of serum enzyme activities.", "content": "1. The effect of demographic variables such as age, sex, body weight, social class and blood pressure upon the activity of serum enzymes in healthy humans is reviewed. A system developed by the author and his colleagues, which automatically adjusts the results of enzyme activity measurements to allow for demographic influences, is described. This allows derivation of a \"demographically corrected\" normal range; for most enzymes this range is much narrower than that provided by the conventional mean +/- 2 SD approach. 2. The influence of precision and analytical factors upon the normal range for serum enzymes is discussed. Data from a British national quality-control survey reveal a depressing picture of interlaboratory precision for commonly determined enzyme estimations. Examples are given (serum aspartate aminotransferase and guanase) which illustrate the influence that precision of a method may have on the normal range for that enzyme.", "contents": "Demographic and analytic factors affecting the normal range of serum enzyme activities. 1. The effect of demographic variables such as age, sex, body weight, social class and blood pressure upon the activity of serum enzymes in healthy humans is reviewed. A system developed by the author and his colleagues, which automatically adjusts the results of enzyme activity measurements to allow for demographic influences, is described. This allows derivation of a \"demographically corrected\" normal range; for most enzymes this range is much narrower than that provided by the conventional mean +/- 2 SD approach. 2. The influence of precision and analytical factors upon the normal range for serum enzymes is discussed. Data from a British national quality-control survey reveal a depressing picture of interlaboratory precision for commonly determined enzyme estimations. Examples are given (serum aspartate aminotransferase and guanase) which illustrate the influence that precision of a method may have on the normal range for that enzyme."} {"id": "PMID:1277454", "title": "Analytical toxicology: Applications of element-selective electrolytic conductivity detection for gas chromatography.", "content": "We applied a commercially available microelectrolytic conductivity detector to toxicological problems of qualitative and quantitative analysis by gas chromatography. The detector can be used for the sensitive and selective detection of halogen-, nitrogen-, and sulfur-containing compounds. Relative response in different element-selective detector variables such as reaction gas, reaction catalyst, and furnace temperature can be used to further improve qualitative identification by gas chromatography.", "contents": "Analytical toxicology: Applications of element-selective electrolytic conductivity detection for gas chromatography. We applied a commercially available microelectrolytic conductivity detector to toxicological problems of qualitative and quantitative analysis by gas chromatography. The detector can be used for the sensitive and selective detection of halogen-, nitrogen-, and sulfur-containing compounds. Relative response in different element-selective detector variables such as reaction gas, reaction catalyst, and furnace temperature can be used to further improve qualitative identification by gas chromatography."} {"id": "PMID:1277455", "title": "Radioimmunoassay, enzyme immunoassay, spectrophotometry, and gas-liquid chromatography compared for determination of phenobarbital and diphenylhydantoin.", "content": "Sera from epileptic patients were assayed for phenobarbital and diphenylhydantoin by four different analytical procedures. Quantitative results obtained by radioimmunoassay (I) and enzyme immunoassay (II) were compared to each other and to the results obtained on aliquots of the same sample by gas-liquid chromatography (III) and ultraviolet spectrophotometry (IV). For phenobarbital the correlation coefficients were I vs. II, 0.909; I vs. III, 0.947; II vs. III, 0.917; I vs. IV, 0.950; II vs. IV, 0.953. For diphenylhydantoin the correlation coefficients were I vs. II, 0.953; I vs. III, 0.951; II vs. III, 0.957; I vs. IV, 0.862; II vs. IV, 0.898. The immunoassays can be substituted for liquid chromatography or ultraviolet spectrophotometry without changing the resulting clinical interpretations.", "contents": "Radioimmunoassay, enzyme immunoassay, spectrophotometry, and gas-liquid chromatography compared for determination of phenobarbital and diphenylhydantoin. Sera from epileptic patients were assayed for phenobarbital and diphenylhydantoin by four different analytical procedures. Quantitative results obtained by radioimmunoassay (I) and enzyme immunoassay (II) were compared to each other and to the results obtained on aliquots of the same sample by gas-liquid chromatography (III) and ultraviolet spectrophotometry (IV). For phenobarbital the correlation coefficients were I vs. II, 0.909; I vs. III, 0.947; II vs. III, 0.917; I vs. IV, 0.950; II vs. IV, 0.953. For diphenylhydantoin the correlation coefficients were I vs. II, 0.953; I vs. III, 0.951; II vs. III, 0.957; I vs. IV, 0.862; II vs. IV, 0.898. The immunoassays can be substituted for liquid chromatography or ultraviolet spectrophotometry without changing the resulting clinical interpretations."} {"id": "PMID:1277456", "title": "Efficacy of activated charcoal hemoperfusion in removing lethal doses of barbiturates and salicylate from the blood of rats and dogs.", "content": "Rats were injected intraperitoneally with lethal doses of sodium pentobarbital (115 mg/kg) or a lethal mixture of sodium salicylate (500 mg/kg) and sodium acetazolamide (25 mg/kg). Within about 20 min, part of each group was connected to an extracorporeal circuit containing uncoated activated charcoal and part to an empty control circuit. After a 90-min hemoperfusion, the treated groups showed a significantly decreased mortality (58% to 14% for pentobarbital; 100% to 0% for salicylate). Dogs were injected intravenously with lethal doses of sodium phenobarbital (175 mg/kg). One group was treated by hemoperfusion through an empty device in a control extracorporeal circuit, a second group was treated with loose-bed activated charcoal devices, and a third group with fixed-bed activated charcoal devices. For both the fixed and loose-bed devices, a 5-h hemoperfusion markedly decreased mortality (100% to less than or equal to 15%). The lethal combination of salicylate and closed-circuit methoxyflurane anesthesia was also successfully treated in dogs. This study clearly demonstrates the lifesaving potential of uncoated activated charcoal hemoperfusion.", "contents": "Efficacy of activated charcoal hemoperfusion in removing lethal doses of barbiturates and salicylate from the blood of rats and dogs. Rats were injected intraperitoneally with lethal doses of sodium pentobarbital (115 mg/kg) or a lethal mixture of sodium salicylate (500 mg/kg) and sodium acetazolamide (25 mg/kg). Within about 20 min, part of each group was connected to an extracorporeal circuit containing uncoated activated charcoal and part to an empty control circuit. After a 90-min hemoperfusion, the treated groups showed a significantly decreased mortality (58% to 14% for pentobarbital; 100% to 0% for salicylate). Dogs were injected intravenously with lethal doses of sodium phenobarbital (175 mg/kg). One group was treated by hemoperfusion through an empty device in a control extracorporeal circuit, a second group was treated with loose-bed activated charcoal devices, and a third group with fixed-bed activated charcoal devices. For both the fixed and loose-bed devices, a 5-h hemoperfusion markedly decreased mortality (100% to less than or equal to 15%). The lethal combination of salicylate and closed-circuit methoxyflurane anesthesia was also successfully treated in dogs. This study clearly demonstrates the lifesaving potential of uncoated activated charcoal hemoperfusion."} {"id": "PMID:1277457", "title": "Rapid radioisotopic procedure for determination of nortriptyline in plasma.", "content": "With the widespread use of tricyclic antidepressant drugs, the relationship between the concentration of the drug in the plasma and the therapeutic response is of considerable interest. We describe a double-isotope derivative dilution procedure for measuring plasma nortriptyline. In the method, [14C]nortriptyline is used for estimating procedural losses and [3H]acetic anhydride for derivative formation. The assay is rapid and adequately specific, sensitive, precies, and reproducible for routine clinical use. We used it to investigate the variation in steady-state drug concentrations in plasma of persons who were on a 150 mg/day dose of nortriptyline. Intra-individual variation from day to day was 10-14%. This variation was not significantly affected by the dosage schedule, the time of sampling after an oral dose, or the storage of the plasma samples. For 19 patients on 150 mg of nortriptyline per day, the mean concentration in plasma was 181 +/- 22 (SE) mug/liter, a value that compares well with our previous findings and those of other groups.", "contents": "Rapid radioisotopic procedure for determination of nortriptyline in plasma. With the widespread use of tricyclic antidepressant drugs, the relationship between the concentration of the drug in the plasma and the therapeutic response is of considerable interest. We describe a double-isotope derivative dilution procedure for measuring plasma nortriptyline. In the method, [14C]nortriptyline is used for estimating procedural losses and [3H]acetic anhydride for derivative formation. The assay is rapid and adequately specific, sensitive, precies, and reproducible for routine clinical use. We used it to investigate the variation in steady-state drug concentrations in plasma of persons who were on a 150 mg/day dose of nortriptyline. Intra-individual variation from day to day was 10-14%. This variation was not significantly affected by the dosage schedule, the time of sampling after an oral dose, or the storage of the plasma samples. For 19 patients on 150 mg of nortriptyline per day, the mean concentration in plasma was 181 +/- 22 (SE) mug/liter, a value that compares well with our previous findings and those of other groups."} {"id": "PMID:1277458", "title": "Gas-chromatographic micro-scale procedure for theophylline, with use of a nitrogen-sensitive detector.", "content": "We report a micro-scale procedure for determination of theophylline by use of gas chromatography with nitrogen-sensitive detection. The procedure requires only 10 mul of serum, plasma, or saliva. This sample size makes the determination especially appropriate for monitoring in a pediatric population. With the sample volume used, background interference is equivalent to about 0.1 mg/liter and 0.5 mg of theophylline per liter can easily be measured. The new method correlates well with our earlier flame ionization gas-chromatographic procedure that required 1 ml of sample [Clin. Chem. 21, 1038 (1975)]. The selectiviey of the nitrogen detector allows a simplified extraction procedure. Between-run precision (CV) is 2.8% at a theophylline concentration of 14.8 mg/liter.", "contents": "Gas-chromatographic micro-scale procedure for theophylline, with use of a nitrogen-sensitive detector. We report a micro-scale procedure for determination of theophylline by use of gas chromatography with nitrogen-sensitive detection. The procedure requires only 10 mul of serum, plasma, or saliva. This sample size makes the determination especially appropriate for monitoring in a pediatric population. With the sample volume used, background interference is equivalent to about 0.1 mg/liter and 0.5 mg of theophylline per liter can easily be measured. The new method correlates well with our earlier flame ionization gas-chromatographic procedure that required 1 ml of sample [Clin. Chem. 21, 1038 (1975)]. The selectiviey of the nitrogen detector allows a simplified extraction procedure. Between-run precision (CV) is 2.8% at a theophylline concentration of 14.8 mg/liter."} {"id": "PMID:1277459", "title": "Simultaneous gas-chromatographic analysis for phenobarbital, diphenylhydantoin, carbamazepine, and primidone in serum.", "content": "We describe a simple, sensitive determination of phenobarbital, diphenylhydantoin, carbamazepine, and primidone in serum, by use of gas-liquid chromatography with temperature programming. The methylated derivatives of these anticonvulsants are well resolved, as was 5-(p-methyl-phenyl)-5-phenylhydantoin, the internal standard. The proposed procedure requires only 0.20 ml of serum and can be done in less than 30 min. The lower limit of detection for each of the drugs is 0.5 mg/liter. Analytical recoveries of drug from serum were excellent and peak height and concentration were linearly related up to twice the toxic concentration for serum.", "contents": "Simultaneous gas-chromatographic analysis for phenobarbital, diphenylhydantoin, carbamazepine, and primidone in serum. We describe a simple, sensitive determination of phenobarbital, diphenylhydantoin, carbamazepine, and primidone in serum, by use of gas-liquid chromatography with temperature programming. The methylated derivatives of these anticonvulsants are well resolved, as was 5-(p-methyl-phenyl)-5-phenylhydantoin, the internal standard. The proposed procedure requires only 0.20 ml of serum and can be done in less than 30 min. The lower limit of detection for each of the drugs is 0.5 mg/liter. Analytical recoveries of drug from serum were excellent and peak height and concentration were linearly related up to twice the toxic concentration for serum."} {"id": "PMID:1277460", "title": "Gas-chromatographic determination of 5-fluorocytosine in human serum.", "content": "We describe a sensitive and precise gas-chromatographic method, in which cytosine is used as the internal standard, for determination of an antifungal agent, 5-fluorocytosine, in serum. The trimethylsilyl derivative of this drug is well separated from the internal standard and from normal serum constituents. Amphotericin B does not interfere with the determination of 5-fluorocytosine. The lower limit of detection for 5-fluorocytosine is 1 mg/liter when 200 mul of serum is analyzed. Within-run precision (CV), established by analysis of 10 replicates, was 4.5% at a concentration of 19.9 mg/liter. Twenty-five serum samples were analyzed for 5-fluorocytosine by a microbiological assay and by the gas-chromatographic method. Mean value observed with the bioassay was 78.5 mg/liter and with our procedure was 69.4 mg/liter. When values for our assay were regressed against values for the bioassay, slope of the least-squares line was 0.85, intercept was 2.7 mg/liter, and r was 0.93.", "contents": "Gas-chromatographic determination of 5-fluorocytosine in human serum. We describe a sensitive and precise gas-chromatographic method, in which cytosine is used as the internal standard, for determination of an antifungal agent, 5-fluorocytosine, in serum. The trimethylsilyl derivative of this drug is well separated from the internal standard and from normal serum constituents. Amphotericin B does not interfere with the determination of 5-fluorocytosine. The lower limit of detection for 5-fluorocytosine is 1 mg/liter when 200 mul of serum is analyzed. Within-run precision (CV), established by analysis of 10 replicates, was 4.5% at a concentration of 19.9 mg/liter. Twenty-five serum samples were analyzed for 5-fluorocytosine by a microbiological assay and by the gas-chromatographic method. Mean value observed with the bioassay was 78.5 mg/liter and with our procedure was 69.4 mg/liter. When values for our assay were regressed against values for the bioassay, slope of the least-squares line was 0.85, intercept was 2.7 mg/liter, and r was 0.93."} {"id": "PMID:1277461", "title": "Gas-chromatographic analysis for therapeutic concentrations of amitriptyline and nortriptyline in plasma, with use of a nitrogen detector.", "content": "We describe a gas-chromatographic procedure for the simultaneous determination of amitriptyline and its active metabolite, nortriptyline, in therapeutic concentrations in human plasma, with use of a nitrogen detector. Both drugs are extracted at pH 10.5 into hexane/isoamyl alcohol, back-extracted into dilute HCl, and re-extracted into hexane/isoamyl alcohol after alkalinization of the HCl. The solvent is evaporated and the residue gas-chromatographed. Protriptyline is used as the internal standard. As little as 5 mug of amitriptyline or nortriptyline can be detected per liter of plasma. The coefficients of variation, for a concentration of 200 mug/liter, are 4.6% and 4.3% within-day and 8.6% and 3.4% day-to-day for amitriptyline and nortriptyline, respectively. The procedure was applied to patients receiving therapeutic doses of both drugs and also to patients who had taken overdoses of amitriptyline.", "contents": "Gas-chromatographic analysis for therapeutic concentrations of amitriptyline and nortriptyline in plasma, with use of a nitrogen detector. We describe a gas-chromatographic procedure for the simultaneous determination of amitriptyline and its active metabolite, nortriptyline, in therapeutic concentrations in human plasma, with use of a nitrogen detector. Both drugs are extracted at pH 10.5 into hexane/isoamyl alcohol, back-extracted into dilute HCl, and re-extracted into hexane/isoamyl alcohol after alkalinization of the HCl. The solvent is evaporated and the residue gas-chromatographed. Protriptyline is used as the internal standard. As little as 5 mug of amitriptyline or nortriptyline can be detected per liter of plasma. The coefficients of variation, for a concentration of 200 mug/liter, are 4.6% and 4.3% within-day and 8.6% and 3.4% day-to-day for amitriptyline and nortriptyline, respectively. The procedure was applied to patients receiving therapeutic doses of both drugs and also to patients who had taken overdoses of amitriptyline."} {"id": "PMID:1277462", "title": "Liquid chromatographic method for monitoring therapeutic concentrations of L-dopa and dopamine in serum.", "content": "We describe a new method for the simultaneous assay of 3,4-dihydroxyphenylalanine (L-dopa) and dopamine in serum. Both compounds have been determined quantitatively at concentrations as low as 10 mug/liter with a coefficient of variation of less than 4%. Peak heights were linearly related to concentration up to 10 mg/liter for each compound. Assay of human sera gave within-run and day-to-day coefficients of variation of 2.8% and 3.1% for L-dopa, and 2.9% and 3.7% for dopamine. The linear relationship between readings nA, y-axis) and concentration (mug/liter) is described by the following equations: y = (21.0 +/- 0.082)x + (0.46 +/- 0.31 SD) for L-dopa and y = (17.0 +/- 0.10)x + (0.08 +/- 0.04 SD) for dopamine. The procedure combines liquid/solid extraction, liquid chromatography, and controlled-potential electrochemistry. The simplicity, sensitivity, and accuracy of this method make it suitable for routine clinical analysis of serum samples to optimize bioavailability for individual patients. After the extraction procedure is completed, samples can be analyzed at the rate of 10/h.", "contents": "Liquid chromatographic method for monitoring therapeutic concentrations of L-dopa and dopamine in serum. We describe a new method for the simultaneous assay of 3,4-dihydroxyphenylalanine (L-dopa) and dopamine in serum. Both compounds have been determined quantitatively at concentrations as low as 10 mug/liter with a coefficient of variation of less than 4%. Peak heights were linearly related to concentration up to 10 mg/liter for each compound. Assay of human sera gave within-run and day-to-day coefficients of variation of 2.8% and 3.1% for L-dopa, and 2.9% and 3.7% for dopamine. The linear relationship between readings nA, y-axis) and concentration (mug/liter) is described by the following equations: y = (21.0 +/- 0.082)x + (0.46 +/- 0.31 SD) for L-dopa and y = (17.0 +/- 0.10)x + (0.08 +/- 0.04 SD) for dopamine. The procedure combines liquid/solid extraction, liquid chromatography, and controlled-potential electrochemistry. The simplicity, sensitivity, and accuracy of this method make it suitable for routine clinical analysis of serum samples to optimize bioavailability for individual patients. After the extraction procedure is completed, samples can be analyzed at the rate of 10/h."} {"id": "PMID:1277463", "title": "Relative merits of some methods for amphetamine assay in biological fluids.", "content": "We describe principles and details that we use for amphetamine determination in blood and urine by photometric, thin-layer chromatographic, gas-chromatographic, and immunologic (EMIT and radioimmunoassay) procedures. Results, interferences, stabilities, and economic considerations are intercompared and recommendations are made.", "contents": "Relative merits of some methods for amphetamine assay in biological fluids. We describe principles and details that we use for amphetamine determination in blood and urine by photometric, thin-layer chromatographic, gas-chromatographic, and immunologic (EMIT and radioimmunoassay) procedures. Results, interferences, stabilities, and economic considerations are intercompared and recommendations are made."} {"id": "PMID:1277464", "title": "Automated enzymic determination of ethanol in blood, serum, and urine with a miniature centrifugal analyzer.", "content": "We describe an automated spectrophotometric reaction-rate method for determination of ethanol in serum and urine with a miniature centrifugal analyzer. The theanol is selectively oxidized in the presence of alcochol dehydrogenase and NAD+ to form NADH, which is measured by the rate of change of its absorbance. Reaction rates are determined automatically, and unknown concentrations are calculated from a computer-generated working curve based on aqueous ethanol standards. Blood, serum, or urine specimens need not be deproteinized. The method permits duplicate analysis of at least 30 samples per hour. Coefficients of variation and relative errors are about 2-3% for ethanol concentrations of 0.3-3.0 mug per 2 mul of sample. Analytical recovery of ethanol added to serum is 92-103% (average, 98.5%). Comparisons with distillation-oxidation, gas-chromatographic, and conventional enzymic procedures give satisfactory agreement.", "contents": "Automated enzymic determination of ethanol in blood, serum, and urine with a miniature centrifugal analyzer. We describe an automated spectrophotometric reaction-rate method for determination of ethanol in serum and urine with a miniature centrifugal analyzer. The theanol is selectively oxidized in the presence of alcochol dehydrogenase and NAD+ to form NADH, which is measured by the rate of change of its absorbance. Reaction rates are determined automatically, and unknown concentrations are calculated from a computer-generated working curve based on aqueous ethanol standards. Blood, serum, or urine specimens need not be deproteinized. The method permits duplicate analysis of at least 30 samples per hour. Coefficients of variation and relative errors are about 2-3% for ethanol concentrations of 0.3-3.0 mug per 2 mul of sample. Analytical recovery of ethanol added to serum is 92-103% (average, 98.5%). Comparisons with distillation-oxidation, gas-chromatographic, and conventional enzymic procedures give satisfactory agreement."} {"id": "PMID:1277465", "title": "Gas-chromatographic determination of an antifibrinolytic drug, epsilon-aminocaproic acid.", "content": "We describe a modified method for assay of epsilon-aminocaproic acid. Serum or cerebrospinal fluid is deproteinized, followed by cation-exchange column-chromatography, and N-trifluoroacetyl-n-butyl derivatives of amino acids are formed and separated by gas chromatography. Tranexamic acid, a nonprotein amino acid, was used as an internal standard. The assay is sensitive and precise, and results correlate adequately with those obtained with an automated amino acid analyzer (ion-exchange chromatography).", "contents": "Gas-chromatographic determination of an antifibrinolytic drug, epsilon-aminocaproic acid. We describe a modified method for assay of epsilon-aminocaproic acid. Serum or cerebrospinal fluid is deproteinized, followed by cation-exchange column-chromatography, and N-trifluoroacetyl-n-butyl derivatives of amino acids are formed and separated by gas chromatography. Tranexamic acid, a nonprotein amino acid, was used as an internal standard. The assay is sensitive and precise, and results correlate adequately with those obtained with an automated amino acid analyzer (ion-exchange chromatography)."} {"id": "PMID:1277466", "title": "Serum quinidine concentrations: comparison of fluorescence, gas-chromatographic, and gas-chromatographic/mass-spectrometric methods.", "content": "Serum quinidine concentrations were determined in patients on chronic therapeutic doses. Although results were higher by a protein precipitate-fluorescence method as compared to a specific extraction fluorescence method, there was substantial correlation between results by the two methods (r = 0.945, P less than 0.001). We established the specificity of the extraction method by a methylation gas-chromatographic method in which the base peak in the mass spectra of the methylated products of both quinidine and cinchonidine, the internal standard, was monitored. We conclude that the protein precipitate method should be discarded.", "contents": "Serum quinidine concentrations: comparison of fluorescence, gas-chromatographic, and gas-chromatographic/mass-spectrometric methods. Serum quinidine concentrations were determined in patients on chronic therapeutic doses. Although results were higher by a protein precipitate-fluorescence method as compared to a specific extraction fluorescence method, there was substantial correlation between results by the two methods (r = 0.945, P less than 0.001). We established the specificity of the extraction method by a methylation gas-chromatographic method in which the base peak in the mass spectra of the methylated products of both quinidine and cinchonidine, the internal standard, was monitored. We conclude that the protein precipitate method should be discarded."} {"id": "PMID:1277467", "title": "Simultaneous measurement of phenobarbital, diphenylhydantoin, and primidone in blood by high-pressure liquid chromatography.", "content": "We describe a sensitive, precise high-pressure liquid chromatographic method in which 5-(p-methylphenyl)-5-phenylhydantoin is used as the internal standard for simultaneous determination of diphenylhydantoin, phenobarbital, and primidone in whole blood and plasma. These anticonvulsant drugs are well separated from each other and from normal blood constituents in less than 10 min. The lower limit of detection for each drug is 100 ng for primidone, 200 ng for dilantin, and 300 ng for phenobarbital. The eluted drugs were detected by their absorption at 254 nm, and evaluated from their peak heights as compared to internal standard. The method was successfully adapted for pediatric samples (100 to 500 mul of whole blood or plasma). Fifty specimens were analyzed for phenobarbital and diphenylhydantoin and 25 specimens for primidone by a standard gas-chromatographic method and by our liquid-chromatographic method; the resulting correlation coefficient was greater than 0.98.", "contents": "Simultaneous measurement of phenobarbital, diphenylhydantoin, and primidone in blood by high-pressure liquid chromatography. We describe a sensitive, precise high-pressure liquid chromatographic method in which 5-(p-methylphenyl)-5-phenylhydantoin is used as the internal standard for simultaneous determination of diphenylhydantoin, phenobarbital, and primidone in whole blood and plasma. These anticonvulsant drugs are well separated from each other and from normal blood constituents in less than 10 min. The lower limit of detection for each drug is 100 ng for primidone, 200 ng for dilantin, and 300 ng for phenobarbital. The eluted drugs were detected by their absorption at 254 nm, and evaluated from their peak heights as compared to internal standard. The method was successfully adapted for pediatric samples (100 to 500 mul of whole blood or plasma). Fifty specimens were analyzed for phenobarbital and diphenylhydantoin and 25 specimens for primidone by a standard gas-chromatographic method and by our liquid-chromatographic method; the resulting correlation coefficient was greater than 0.98."} {"id": "PMID:1277468", "title": "Radioimmunoassay for clindamycin.", "content": "We describe a radioimmunoassay for measuring clindamycin in serum extracts that is more accurate than the microbiological assay because of the minimal response of the matabolite, N-demethylclindamycin. The assay is not affected by the presence of other antiobiotics. As described it is as sensitive as the microbiological assay, but can be made more sensitive.", "contents": "Radioimmunoassay for clindamycin. We describe a radioimmunoassay for measuring clindamycin in serum extracts that is more accurate than the microbiological assay because of the minimal response of the matabolite, N-demethylclindamycin. The assay is not affected by the presence of other antiobiotics. As described it is as sensitive as the microbiological assay, but can be made more sensitive."} {"id": "PMID:1277469", "title": "Assessment of interference by aspirin with some assays commonly done in the clinical laboratory.", "content": "We have assessed the interference of acetylsalicylic acid (aspirin) with some common clinical laboratory assays, because of its widespread use and reported interference. The therapeutic regimens involved ingestion of 10 325-mg tablets daily for three days or eight tablets for five days or two weeks. Twenty-one commonly done determinations were run on control sera, and sera were collected during and after drug therapy. Significant changes in t-test values, indicating the significance of the standard deviation of the difference between controls and specimens drawn after drug therapy, were observed for chloride (increased), and for total protein, calcium, cholesterol, uric acid, bilirubin, and thyroxine (decreased). Aspirin therapy depressed the apparent concentrations of these constituents progressively in the three-day regimen and initially in the long-term regimens, followed by recovery toward zero t-values at the end of the longer regimens.", "contents": "Assessment of interference by aspirin with some assays commonly done in the clinical laboratory. We have assessed the interference of acetylsalicylic acid (aspirin) with some common clinical laboratory assays, because of its widespread use and reported interference. The therapeutic regimens involved ingestion of 10 325-mg tablets daily for three days or eight tablets for five days or two weeks. Twenty-one commonly done determinations were run on control sera, and sera were collected during and after drug therapy. Significant changes in t-test values, indicating the significance of the standard deviation of the difference between controls and specimens drawn after drug therapy, were observed for chloride (increased), and for total protein, calcium, cholesterol, uric acid, bilirubin, and thyroxine (decreased). Aspirin therapy depressed the apparent concentrations of these constituents progressively in the three-day regimen and initially in the long-term regimens, followed by recovery toward zero t-values at the end of the longer regimens."} {"id": "PMID:1277470", "title": "Results of a nine-laboratory survey of forensic toxicology proficiency.", "content": "Toxicological determinations are crucial to coroners' or medical examiners' judgments that drugs are significantly involved in a death. However, differences in laboratory procedures, thoroughness of screening, and limits of detection may result in artifactual differences in the toxicological results and the subsequent interpretations of them. To test this possibility, we conducted a toxicology proficiency-testing survey of nine collaborating laboratories. The results for the proficiency samples point out starting interlaboratory differences in accuracy and precision of detection of drugs. These observed variations in toxicological proficiency may introduce a significant source of error in drug-death statistics and in epidemiological deductions based on these statistics.", "contents": "Results of a nine-laboratory survey of forensic toxicology proficiency. Toxicological determinations are crucial to coroners' or medical examiners' judgments that drugs are significantly involved in a death. However, differences in laboratory procedures, thoroughness of screening, and limits of detection may result in artifactual differences in the toxicological results and the subsequent interpretations of them. To test this possibility, we conducted a toxicology proficiency-testing survey of nine collaborating laboratories. The results for the proficiency samples point out starting interlaboratory differences in accuracy and precision of detection of drugs. These observed variations in toxicological proficiency may introduce a significant source of error in drug-death statistics and in epidemiological deductions based on these statistics."} {"id": "PMID:1277471", "title": "Analysis of results of toxicological examinations performed by coroners' or medical examiners' laboratories in 2000 drug-involved deaths in nine major U. S. cities.", "content": "Data were collected on 2000 deaths in which psychoactive drugs were involved. The data were submitted by medical examiners or coroners in nine U. S. cities from their case files. The 2000 cases comprise a representative sample from each of these cities of deaths from psychoactive drugs between 1972 through 1974. This report details inter-city differences in methods and practices of the toxicological examination as well as the type and numbers of drugs reported. Even when the same analytical method was used in various cities, there were differences in extraction solvent and extraction pH. Of the 3909 drugs detected, 2945 were quantitated; the number of drugs quantitatively measured per case studied ranged from a low of 0.82 for New York to a high of 2.20 for Washington, D.C. The number of different drugs quantitatively measured varied from 16 for New York to 30 for San Francisco; however, New York qualitatively assayed for the presence of a total of 25 drugs. The number and type of drugs found per case varied. Methadone, for example, was found in 60% of the cases reported by New York and in 49% of the cases from Washington, D.C., but in only about 10% of cases reported by Philadelphia, Dallas, Miami, and San Francisco, and in less than 1% of Los Angeles and Cleveland cases; it was not reported by Chicago. Phenmetrazine-caused deaths were reported only by Dallas (one case) and Washington, D.C. (29 cases). From the data as a whole, information is presented for 33 drugs as to the concentration in physiological tissues and fluids. Analysis of single psychoactive drug cases and single-drug-plus-ethanol cases shows that, in the presence of ethanol, the toxic blood concentration of imipramine, amytriptyline, meprobamate, thioridazine, morphine, propoxyphene, methaqualone, and all barbiturates was decreased by an average of 50%.", "contents": "Analysis of results of toxicological examinations performed by coroners' or medical examiners' laboratories in 2000 drug-involved deaths in nine major U. S. cities. Data were collected on 2000 deaths in which psychoactive drugs were involved. The data were submitted by medical examiners or coroners in nine U. S. cities from their case files. The 2000 cases comprise a representative sample from each of these cities of deaths from psychoactive drugs between 1972 through 1974. This report details inter-city differences in methods and practices of the toxicological examination as well as the type and numbers of drugs reported. Even when the same analytical method was used in various cities, there were differences in extraction solvent and extraction pH. Of the 3909 drugs detected, 2945 were quantitated; the number of drugs quantitatively measured per case studied ranged from a low of 0.82 for New York to a high of 2.20 for Washington, D.C. The number of different drugs quantitatively measured varied from 16 for New York to 30 for San Francisco; however, New York qualitatively assayed for the presence of a total of 25 drugs. The number and type of drugs found per case varied. Methadone, for example, was found in 60% of the cases reported by New York and in 49% of the cases from Washington, D.C., but in only about 10% of cases reported by Philadelphia, Dallas, Miami, and San Francisco, and in less than 1% of Los Angeles and Cleveland cases; it was not reported by Chicago. Phenmetrazine-caused deaths were reported only by Dallas (one case) and Washington, D.C. (29 cases). From the data as a whole, information is presented for 33 drugs as to the concentration in physiological tissues and fluids. Analysis of single psychoactive drug cases and single-drug-plus-ethanol cases shows that, in the presence of ethanol, the toxic blood concentration of imipramine, amytriptyline, meprobamate, thioridazine, morphine, propoxyphene, methaqualone, and all barbiturates was decreased by an average of 50%."} {"id": "PMID:1277472", "title": "Serum theophylline analysis by high-pressure liquid chromatography.", "content": "We have developed and evaluated a rapid, high-pressure liquid-chromatographic method for theophylline in serum. Only 0.2 ml of serum is required for each determination, and the sensitivity of this method is 0.5 mg/liter. This method, involving liquid extraction and silica adsorption chromatography, provides adequate selectivity, accuracy, and precision for routine or research applications. Little sample preparation is required before chromatography. We found no endogenous or exogenous interferences. Use of beta-hydroxypropyl theophylline as the internal standard provides reproducible results for this micro-scale method.", "contents": "Serum theophylline analysis by high-pressure liquid chromatography. We have developed and evaluated a rapid, high-pressure liquid-chromatographic method for theophylline in serum. Only 0.2 ml of serum is required for each determination, and the sensitivity of this method is 0.5 mg/liter. This method, involving liquid extraction and silica adsorption chromatography, provides adequate selectivity, accuracy, and precision for routine or research applications. Little sample preparation is required before chromatography. We found no endogenous or exogenous interferences. Use of beta-hydroxypropyl theophylline as the internal standard provides reproducible results for this micro-scale method."} {"id": "PMID:1277473", "title": "Rapid micromethod for measuring anticonvulsant drugs in serum by high-performance liquid chromatography.", "content": "We describe an assay system for measuring phenobarbital, diphenylhydantoin, primidone, ethosuximide, and carbamazepine in 25 mul of serum. The procedure involves precipitation of proteins with an acetonitrile solution containing cyheptamide as an internal standard, and reverse-phase chromatography on a 4 mm X 30 cm column containing \"muBondapak C18.\" The anticonvulsants are eluted with an equivolume mixture of potassium phosphate buffer (10 mmol/liter, pH 8.0) and acetonitrile at a flow rate of 0.8 ml/min, detected by their absorbance at 200 nm, and quantitated by measuring peak areas. When measurement of primidone is not required, a 254-nm detector may be used. Each analysis requires 10 min. Optimum column temperature has been found to decrease with use. Analytical recoveries for the five drugs varied from 92% to 102% with good precision (coefficients of variation between 2.8% and 9.2% for therapeutic and toxic concentrations). The results obtained with this method compare favorably with results obtained by gas-liquid chromatography (correlation coefficients between 0.77 and 0.98). In over 1300 patients' samples analyzed to date, the only drugs known to have interfered with the assay are gentamicin, diazoxide, and mephobarbital.", "contents": "Rapid micromethod for measuring anticonvulsant drugs in serum by high-performance liquid chromatography. We describe an assay system for measuring phenobarbital, diphenylhydantoin, primidone, ethosuximide, and carbamazepine in 25 mul of serum. The procedure involves precipitation of proteins with an acetonitrile solution containing cyheptamide as an internal standard, and reverse-phase chromatography on a 4 mm X 30 cm column containing \"muBondapak C18.\" The anticonvulsants are eluted with an equivolume mixture of potassium phosphate buffer (10 mmol/liter, pH 8.0) and acetonitrile at a flow rate of 0.8 ml/min, detected by their absorbance at 200 nm, and quantitated by measuring peak areas. When measurement of primidone is not required, a 254-nm detector may be used. Each analysis requires 10 min. Optimum column temperature has been found to decrease with use. Analytical recoveries for the five drugs varied from 92% to 102% with good precision (coefficients of variation between 2.8% and 9.2% for therapeutic and toxic concentrations). The results obtained with this method compare favorably with results obtained by gas-liquid chromatography (correlation coefficients between 0.77 and 0.98). In over 1300 patients' samples analyzed to date, the only drugs known to have interfered with the assay are gentamicin, diazoxide, and mephobarbital."} {"id": "PMID:1277474", "title": "Rapid gas-chromatographic measurement of anticonvulsant drugs in serum.", "content": "We describe a rapid method for precisely measuring concentrations of anticonvulsant drugs in serum. The simple procedure, adaptable to the clinical laboratory, can be used for the routine simultaneous measurement in sera of phenobarbital, primidone, dephenylhydantoin, and (or) ethosuximide. The extraction procedure requires no solvent evaporation and gives a good yield for primidone and quantitative extraction for the other drugs. The relatively small amount of \"early phenobarbital\" formed during on-column methylation permits a precise analysis of phenobarbital based on a single peak. Results can be made available directly, without manual measurements or calculations.", "contents": "Rapid gas-chromatographic measurement of anticonvulsant drugs in serum. We describe a rapid method for precisely measuring concentrations of anticonvulsant drugs in serum. The simple procedure, adaptable to the clinical laboratory, can be used for the routine simultaneous measurement in sera of phenobarbital, primidone, dephenylhydantoin, and (or) ethosuximide. The extraction procedure requires no solvent evaporation and gives a good yield for primidone and quantitative extraction for the other drugs. The relatively small amount of \"early phenobarbital\" formed during on-column methylation permits a precise analysis of phenobarbital based on a single peak. Results can be made available directly, without manual measurements or calculations."} {"id": "PMID:1277475", "title": "Method for alcohol determination in biological liquids by sensing with a solid-state detector.", "content": "I describe a new method for quantitative alcohol determination in equilibrated headspace gas of biological liquids by means of a solid-state metal-oxide semiconductor (MOS) detector. After equilibration of the NaCl-saturated specimen at 40 degrees C or other convenient temperature in a closed vessel, a Taguchi MOS sensor is momentarily exposed to the headspace vapor. The resulting dc voltage change from the baseline conditions accurately reflects the alcohol concentration of the liquid specimen, and can be read in direct alcohol-concentration units. Calibration is linear to 3.00 g/liter (300 mg/dl). Values for analytical recovery ranged from 98 to 102%. Correlation of results for blood alcohol concentration by this method (yi) and an automated gas-chromatographic reference method (xi) was y, g/liter = 0.991x + 0.014, with r = 0.997 for 103 blood specimens having concentrations ranging from 0 to 2.89 g/liter (0-289 mg/dl), with a mean difference (xi - yi) - -6 mg/liter (0.6 mg/dl). The method is sensitive to 0.01 g/liter (1 mg/dl) and can be readily automated. An internal standard is not required.", "contents": "Method for alcohol determination in biological liquids by sensing with a solid-state detector. I describe a new method for quantitative alcohol determination in equilibrated headspace gas of biological liquids by means of a solid-state metal-oxide semiconductor (MOS) detector. After equilibration of the NaCl-saturated specimen at 40 degrees C or other convenient temperature in a closed vessel, a Taguchi MOS sensor is momentarily exposed to the headspace vapor. The resulting dc voltage change from the baseline conditions accurately reflects the alcohol concentration of the liquid specimen, and can be read in direct alcohol-concentration units. Calibration is linear to 3.00 g/liter (300 mg/dl). Values for analytical recovery ranged from 98 to 102%. Correlation of results for blood alcohol concentration by this method (yi) and an automated gas-chromatographic reference method (xi) was y, g/liter = 0.991x + 0.014, with r = 0.997 for 103 blood specimens having concentrations ranging from 0 to 2.89 g/liter (0-289 mg/dl), with a mean difference (xi - yi) - -6 mg/liter (0.6 mg/dl). The method is sensitive to 0.01 g/liter (1 mg/dl) and can be readily automated. An internal standard is not required."} {"id": "PMID:1277476", "title": "Gas-chromatographic method for acetaminophen (N-acetyl-p-aminophenol) based on sequential alkylation.", "content": "A gas-chromatographic procedure for acetaminophen is described in which the drug is chromatographed as the O-heptyl-N-methyl derivative. This derivative is prepared by a sequential alkylation procedure in which the phenolic hydroxyl group of the parent compound is alkylated off-column with heptyl iodide and the amide group is derivatized on-column by reaction with trimethylanilinium hydroxide. The internal standard, N-propionyl-p-aminophenol, is subjected to the same derivatization procedure. This gas-chromatographic procedure correlates well with conventional colorimetric and spectrophotometric procedures for acetaminophen and is more sensitive. Within-run precision (CV) was 2.0% at a serum concentration of 10.0 mg/liter (n = 10) and between-run precision was 4.0% over a period of eight months. This method is particularly applicable to studies of the pharmacokinetics of acetaminophen.", "contents": "Gas-chromatographic method for acetaminophen (N-acetyl-p-aminophenol) based on sequential alkylation. A gas-chromatographic procedure for acetaminophen is described in which the drug is chromatographed as the O-heptyl-N-methyl derivative. This derivative is prepared by a sequential alkylation procedure in which the phenolic hydroxyl group of the parent compound is alkylated off-column with heptyl iodide and the amide group is derivatized on-column by reaction with trimethylanilinium hydroxide. The internal standard, N-propionyl-p-aminophenol, is subjected to the same derivatization procedure. This gas-chromatographic procedure correlates well with conventional colorimetric and spectrophotometric procedures for acetaminophen and is more sensitive. Within-run precision (CV) was 2.0% at a serum concentration of 10.0 mg/liter (n = 10) and between-run precision was 4.0% over a period of eight months. This method is particularly applicable to studies of the pharmacokinetics of acetaminophen."} {"id": "PMID:1277477", "title": "Quantitative gas-chromatographic flame-ionization method for p-chlorophenoxyisobutyric acid in human serum and saliva.", "content": "We describe a gas-chromatographic method for p-chlorophenoxyisobutyric acid (I) the active metabolite of clofibrate. The drug and internal standards are separated from either serum or saliva by a double extraction procedure and converted to the corresponding butyl esters by reaction with iodobutane in a mixture of methanol and N,N-di-methylacetamide containing tetramethylammonium hydroxide. Within-run CV of this assay at a serum I concentration of 79.2 mg/liter was 2.3% and at a salivary I concentration of 2.5 mg/liter was 2.1%. Precision during four months of the serum and salivary assays at these concentrations was 4.1% and 6.2%, respectively. The mean serum concentration of I (12 h after dose) in patients receiving the drug at an average dose of 28.0 mg/kg per day was 109.6 mg/liter. Serum and salivary concentrations of I as determined by our procedure were used to calculate the unbound fraction of drug in human serum. Such measurements can be used to monitor therapy in patients with renal disease, where drug toxicity may arise from high concentrations of unbound I.", "contents": "Quantitative gas-chromatographic flame-ionization method for p-chlorophenoxyisobutyric acid in human serum and saliva. We describe a gas-chromatographic method for p-chlorophenoxyisobutyric acid (I) the active metabolite of clofibrate. The drug and internal standards are separated from either serum or saliva by a double extraction procedure and converted to the corresponding butyl esters by reaction with iodobutane in a mixture of methanol and N,N-di-methylacetamide containing tetramethylammonium hydroxide. Within-run CV of this assay at a serum I concentration of 79.2 mg/liter was 2.3% and at a salivary I concentration of 2.5 mg/liter was 2.1%. Precision during four months of the serum and salivary assays at these concentrations was 4.1% and 6.2%, respectively. The mean serum concentration of I (12 h after dose) in patients receiving the drug at an average dose of 28.0 mg/kg per day was 109.6 mg/liter. Serum and salivary concentrations of I as determined by our procedure were used to calculate the unbound fraction of drug in human serum. Such measurements can be used to monitor therapy in patients with renal disease, where drug toxicity may arise from high concentrations of unbound I."} {"id": "PMID:1277478", "title": "Measurement of clomipramine, N-desmethyl-clomipramine, imipramine, and dehydroimipramine in biological fluids by selective ion monitoring, and pharmacokinetics of clomipramine.", "content": "To quantitatively determine tricyclic antidepressant agents, we used a combined gas chromatograph/mass spectrometer system, and deuterium-labeled internal standards. Recovery exceeds 95% and the coefficient of variation is less than 4% for human whole-blood samples supplemented with 5 to 15 ng of clomipramine hydrochloride or 20 to 60 ng of dehydroimipramine hydrogen fumarate per milliliter. For both amines, the detection limit is 0.3 mug/liter; Six healthy volunteers who received a single oral dose of 50 mg of clomipramine hydrochloride showed peak drug concentrations in the blood 3 to 5 h after administration, ranging between 14.4 and 30.1 mug/liter. Plasma/whole blood concentration ratios varied from 0.70 to 1.20, and the cumulative renal elimination from 0 to 72 h is less than 0.2% of the dose. This method is suitable for in vivo bioavailability studies of unchanged clomipramine, dehydroimipramine, and imipramine after a single oral dose of as little as 25 mg.", "contents": "Measurement of clomipramine, N-desmethyl-clomipramine, imipramine, and dehydroimipramine in biological fluids by selective ion monitoring, and pharmacokinetics of clomipramine. To quantitatively determine tricyclic antidepressant agents, we used a combined gas chromatograph/mass spectrometer system, and deuterium-labeled internal standards. Recovery exceeds 95% and the coefficient of variation is less than 4% for human whole-blood samples supplemented with 5 to 15 ng of clomipramine hydrochloride or 20 to 60 ng of dehydroimipramine hydrogen fumarate per milliliter. For both amines, the detection limit is 0.3 mug/liter; Six healthy volunteers who received a single oral dose of 50 mg of clomipramine hydrochloride showed peak drug concentrations in the blood 3 to 5 h after administration, ranging between 14.4 and 30.1 mug/liter. Plasma/whole blood concentration ratios varied from 0.70 to 1.20, and the cumulative renal elimination from 0 to 72 h is less than 0.2% of the dose. This method is suitable for in vivo bioavailability studies of unchanged clomipramine, dehydroimipramine, and imipramine after a single oral dose of as little as 25 mg."} {"id": "PMID:1277479", "title": "Gas-chromatographic quantitation of theophylline in small volumes of plasma.", "content": "We describe a rapid procedure for quantitating theophylline in 100-mul plasma samples by use of a gas-liquid chromatograph equipped with a flame ionization detector. This methos is especially useful for monitoring theophylline concentrations in serum or plasma of infants, because sufficiently large blood samples can be readily obtained from a heel prick. The method is specific for theophylline in the presence of caffeine, theobromine and phenobarbital. For plasma concentrations equal to or greater than 5 mg/liter the average daily coefficient of variation was less than 7% while the coefficient of variation from day to day was less than 11%. The same approach can also be used to measure concentrations of phenobarbital in small volumes of plasma or serum, and is readily adapted to determination of theophylline and phenobarbital in larger samples.", "contents": "Gas-chromatographic quantitation of theophylline in small volumes of plasma. We describe a rapid procedure for quantitating theophylline in 100-mul plasma samples by use of a gas-liquid chromatograph equipped with a flame ionization detector. This methos is especially useful for monitoring theophylline concentrations in serum or plasma of infants, because sufficiently large blood samples can be readily obtained from a heel prick. The method is specific for theophylline in the presence of caffeine, theobromine and phenobarbital. For plasma concentrations equal to or greater than 5 mg/liter the average daily coefficient of variation was less than 7% while the coefficient of variation from day to day was less than 11%. The same approach can also be used to measure concentrations of phenobarbital in small volumes of plasma or serum, and is readily adapted to determination of theophylline and phenobarbital in larger samples."} {"id": "PMID:1277480", "title": "Primidone analyses: correlation of gas-chromatographic assay with enzyme immunoassay.", "content": "Serum specimens from patients on primidone therapy were assayed by two currently available procedures: a commercially available enzyme immunoassay (EMIT) and a published gas-chromatographic procedure. Both procedures were done with commercially available materials and equipment. Results by the two procedures agreed well, which suggests that the two methods could be used interchangeably. For the 94 specimens studied, the correlation coefficient was 0.98, and the least-squares values of slope and intercept were, respectively, 0.97 and 0.51 mg/liter.", "contents": "Primidone analyses: correlation of gas-chromatographic assay with enzyme immunoassay. Serum specimens from patients on primidone therapy were assayed by two currently available procedures: a commercially available enzyme immunoassay (EMIT) and a published gas-chromatographic procedure. Both procedures were done with commercially available materials and equipment. Results by the two procedures agreed well, which suggests that the two methods could be used interchangeably. For the 94 specimens studied, the correlation coefficient was 0.98, and the least-squares values of slope and intercept were, respectively, 0.97 and 0.51 mg/liter."} {"id": "PMID:1277481", "title": "Improved micro-radioimmunoassay of digoxin in serum, with use of 125I-labeled digoxin.", "content": "A micro-radioimmunoassay of 125I-labeled digoxin is described in which 10-mul rather than 50-mul aliquots of sera are required. The method is a modification of a simplified, rapid, and accurate procedure, which is commercially available as a kit. There is excellent correlation between results by these two methods, in which lyophilized digoxin standards and insoluble antibody polymer are used. The digoxin concentration in capillary sera was not significantly different from that in the corresponding venous blood. It is clinically useful to monitor digoxin therapy in capillary sera, particularly in patients in whom blood sampling by venipuncture is inconvenient or difficult.", "contents": "Improved micro-radioimmunoassay of digoxin in serum, with use of 125I-labeled digoxin. A micro-radioimmunoassay of 125I-labeled digoxin is described in which 10-mul rather than 50-mul aliquots of sera are required. The method is a modification of a simplified, rapid, and accurate procedure, which is commercially available as a kit. There is excellent correlation between results by these two methods, in which lyophilized digoxin standards and insoluble antibody polymer are used. The digoxin concentration in capillary sera was not significantly different from that in the corresponding venous blood. It is clinically useful to monitor digoxin therapy in capillary sera, particularly in patients in whom blood sampling by venipuncture is inconvenient or difficult."} {"id": "PMID:1277482", "title": "Adaptation of \"EMIT\" technique for serum phenobarbital and diphenylhydantoin assays to the miniature centrifugal analyzer.", "content": "We used a miniature centrifugal analyzer in a spectrophotometric rate-measurement mode to determine the anticonvulsant drugs phenobarbital and diphenylhydantoin in serum, by use of a modified enzyme immunoassay (\"EMIT\", Syva Corp.) We decreased reagent cost per determination by at least sixfold by means of microscale techniques. Also, the analysis rate is increased by measuring multiple samples simultaneously. Our method requires only 3 mul of serum for duplicate determinations. Replicate analyses of sera containing phenobarbital and diphenylhydantoin gave reaction rates with a CV of 1.5%. Run-to-run CV was 15%. Analytical recovery for drug-supplemented serum samples was 98%, and results for a series of samples compared well with results obtained by gas chromatography (for phenobarbital, r = 0.95; for diphenylhydantoin, r = 0.91).", "contents": "Adaptation of \"EMIT\" technique for serum phenobarbital and diphenylhydantoin assays to the miniature centrifugal analyzer. We used a miniature centrifugal analyzer in a spectrophotometric rate-measurement mode to determine the anticonvulsant drugs phenobarbital and diphenylhydantoin in serum, by use of a modified enzyme immunoassay (\"EMIT\", Syva Corp.) We decreased reagent cost per determination by at least sixfold by means of microscale techniques. Also, the analysis rate is increased by measuring multiple samples simultaneously. Our method requires only 3 mul of serum for duplicate determinations. Replicate analyses of sera containing phenobarbital and diphenylhydantoin gave reaction rates with a CV of 1.5%. Run-to-run CV was 15%. Analytical recovery for drug-supplemented serum samples was 98%, and results for a series of samples compared well with results obtained by gas chromatography (for phenobarbital, r = 0.95; for diphenylhydantoin, r = 0.91)."} {"id": "PMID:1277483", "title": "Simplified fluorometric assay for diphenylhydantoin in plasma.", "content": "The fluorometric benzophenone procedure for diphenylhydantoin has been simplified by eliminating the need for preliminary extraction of plasma with an organic solvent. Assays are done directly on 0.2 ml of plasma by treating it with alkaline permanganate to form benzophenone, extracting the benzophenone with heptane, and then shaking the heptane layer with sulfuric acid and measuring the fluorescence of the acid layer. The assay is highly reproducible, and adequately sensitive to detect 1 mug of the drug per milliliter of plasma. Fluorometric and gas-liquid chromatographic assays of 154 plasmas gave results that were not significantly different, even in the presence of phenobarbital, other barbiturates and anticonvulsant drugs, or of various tranquilizers and other commonly used drugs. The assay is rapid, the unit cost per assay low.", "contents": "Simplified fluorometric assay for diphenylhydantoin in plasma. The fluorometric benzophenone procedure for diphenylhydantoin has been simplified by eliminating the need for preliminary extraction of plasma with an organic solvent. Assays are done directly on 0.2 ml of plasma by treating it with alkaline permanganate to form benzophenone, extracting the benzophenone with heptane, and then shaking the heptane layer with sulfuric acid and measuring the fluorescence of the acid layer. The assay is highly reproducible, and adequately sensitive to detect 1 mug of the drug per milliliter of plasma. Fluorometric and gas-liquid chromatographic assays of 154 plasmas gave results that were not significantly different, even in the presence of phenobarbital, other barbiturates and anticonvulsant drugs, or of various tranquilizers and other commonly used drugs. The assay is rapid, the unit cost per assay low."} {"id": "PMID:1277485", "title": "Beta-carotene content of certain organs from two patients receiving high doses of beta-carotene.", "content": "We measured carotene in the livers of two patients receiving beta-carotene therapy for photosensitivity. In both patients, the amount of carotene was within reported ranges for patients on normal diets; no abnormal amounts of beta-carotene had accumulated in the livers after oral administration of large amounts of beta-carotene. Light-microscopic examination of the liver (specimen obtained at cholecystectomy) of one patient with erythropoietic protoporphyria and cholesterosis showed findings characteristic of these conditions. Electron-microscopically, semicrystalline inclusions were seen in the mitochondria of the hepatocytes; such inclusions have been reported in several conditions, including erythropoietic protoporphyria and porphyria cutanea tarda, and in control subjects. Microscopic examination of the liver of the other patient, who had Rothmund-Rhomson syndrome and died of acute bacterial meningitis, revealed no abnormalities. The cerebrum of the latter patient contained 13 mug of carotene per kilogram (wet weight) of brain. No previous report of analysis of human brain for carotenoids could be found.", "contents": "Beta-carotene content of certain organs from two patients receiving high doses of beta-carotene. We measured carotene in the livers of two patients receiving beta-carotene therapy for photosensitivity. In both patients, the amount of carotene was within reported ranges for patients on normal diets; no abnormal amounts of beta-carotene had accumulated in the livers after oral administration of large amounts of beta-carotene. Light-microscopic examination of the liver (specimen obtained at cholecystectomy) of one patient with erythropoietic protoporphyria and cholesterosis showed findings characteristic of these conditions. Electron-microscopically, semicrystalline inclusions were seen in the mitochondria of the hepatocytes; such inclusions have been reported in several conditions, including erythropoietic protoporphyria and porphyria cutanea tarda, and in control subjects. Microscopic examination of the liver of the other patient, who had Rothmund-Rhomson syndrome and died of acute bacterial meningitis, revealed no abnormalities. The cerebrum of the latter patient contained 13 mug of carotene per kilogram (wet weight) of brain. No previous report of analysis of human brain for carotenoids could be found."} {"id": "PMID:1277496", "title": "Anomalous behavior of glutathione reductase on dilution.", "content": "Serum glutathione reductase activity decreases on standing at room temperature. Dilution of the sample slows this decay in sera from patients with a variety of clinical disorders, and reverses the inactivation in sera from patients with liver or biliary tract disease. Prolonged contact with dithioeythritol or acetate buffer, pH 6.4, at 4 degrees C prevents spontaneous inactivation of the native serum and abolishes the effect of dilution. These hitherto unreported phenomena are a source of potential inaccuracy in assays for this enzyme. The inactivation may be the result of conformational folding with \"burying\" of active sites, or of molecular aggregation brought about by hydrogen bonding or disulfide bond formation.", "contents": "Anomalous behavior of glutathione reductase on dilution. Serum glutathione reductase activity decreases on standing at room temperature. Dilution of the sample slows this decay in sera from patients with a variety of clinical disorders, and reverses the inactivation in sera from patients with liver or biliary tract disease. Prolonged contact with dithioeythritol or acetate buffer, pH 6.4, at 4 degrees C prevents spontaneous inactivation of the native serum and abolishes the effect of dilution. These hitherto unreported phenomena are a source of potential inaccuracy in assays for this enzyme. The inactivation may be the result of conformational folding with \"burying\" of active sites, or of molecular aggregation brought about by hydrogen bonding or disulfide bond formation."} {"id": "PMID:1277497", "title": "Evaluation of a new system (\"Corvac\") for separating serum from blood for routine laboratory procedures.", "content": "We evaluated the suitability of a new system (\"Corvac,\" Corning) for rapid, complete separation of cell-free serum from whole blood. Twenty-one different clinical chemical procedures were performed on about 1150 paired blood samples, several by more than one method, to afford a more comprehensive evaluation. The tube of clotted blood collected in the conventional manner (\"Vacutainer\") underwent a double centrifugation and served as the control sample, while its paired specimen collected in the new system was processed by a single centrifugation. We evaluated significant differences between the means of the paired samples, the standard deviations of the differences between the means, and the bias of the means for the values of each constituent for each collection method. For several tests we observed differences that were statistically but not clinically significant. Only in the case of lactate dehydrogenase were large differences consistently demonstrated.", "contents": "Evaluation of a new system (\"Corvac\") for separating serum from blood for routine laboratory procedures. We evaluated the suitability of a new system (\"Corvac,\" Corning) for rapid, complete separation of cell-free serum from whole blood. Twenty-one different clinical chemical procedures were performed on about 1150 paired blood samples, several by more than one method, to afford a more comprehensive evaluation. The tube of clotted blood collected in the conventional manner (\"Vacutainer\") underwent a double centrifugation and served as the control sample, while its paired specimen collected in the new system was processed by a single centrifugation. We evaluated significant differences between the means of the paired samples, the standard deviations of the differences between the means, and the bias of the means for the values of each constituent for each collection method. For several tests we observed differences that were statistically but not clinically significant. Only in the case of lactate dehydrogenase were large differences consistently demonstrated."} {"id": "PMID:1277498", "title": "Immobilized glucose oxidase used in the continuous-flow determination of serum glucose.", "content": "We used a tubular glucose-oxidase wall reactor in the \"AutoAnalyzer II\" continuous-flow analytical system to determine glucose in blood serum. Sensitivity was high and wash characteristics were satisfactory with use of a 30-cm tube containing immobilized glucose oxidase. Results compared favorably with those of the conventional free-enzyme method. More than 25000 such assays can be performed with a single enzyme tube, which also shows long-term storage stability. Because of the steady-state chemistry 60 samples can be analyzed per hour. The linearity of the method is excellent and sample interaction from 5.0 to 1.0 g/liter is less than 5%. Results correlate well (greater than 0.993) with those obtained with both the neocuproine method used in the \"SMA 12/60\" multichannel analytical system and the free glucose oxidase method used in the AutoAnalyzer.", "contents": "Immobilized glucose oxidase used in the continuous-flow determination of serum glucose. We used a tubular glucose-oxidase wall reactor in the \"AutoAnalyzer II\" continuous-flow analytical system to determine glucose in blood serum. Sensitivity was high and wash characteristics were satisfactory with use of a 30-cm tube containing immobilized glucose oxidase. Results compared favorably with those of the conventional free-enzyme method. More than 25000 such assays can be performed with a single enzyme tube, which also shows long-term storage stability. Because of the steady-state chemistry 60 samples can be analyzed per hour. The linearity of the method is excellent and sample interaction from 5.0 to 1.0 g/liter is less than 5%. Results correlate well (greater than 0.993) with those obtained with both the neocuproine method used in the \"SMA 12/60\" multichannel analytical system and the free glucose oxidase method used in the AutoAnalyzer."} {"id": "PMID:1277499", "title": "Lactate dehydrogenase activities in serum and plasma.", "content": "We investigated lactate dehydrogenase activity in serum and plasma because of the conflicting data found in the literature. We assayed serum, platelet-rich, and platelet-poor plasma by two colorimetric endpoint methods and by an ultraviolet kinetic procedure. Platelet-poor plasma and serum had essentially the same activities by all three methods, whereas the activity in platelet-rich plasma plasma averaged fourfold that in platelet-poor plasma or serum when the assay was performed under conditions that result in lysis of platelets and release of their lactate dehydrogenase. When measurements were performed in platelet-rich plasma under conditions that prevented lysis of platelets, all three types of specimens gave the same results. This occurred when the osmolality of the reaction mixture was about 240 mOsm/kg of water. At an osmolality of about 120 mOsm, the activity of platelet-rich plasma was substantially lower than that of platelet-poor plasma or serum. If plasma must be used, the sample must first be centrifuged (3000 X g, 15 min) to provide a platelet-free plasma.", "contents": "Lactate dehydrogenase activities in serum and plasma. We investigated lactate dehydrogenase activity in serum and plasma because of the conflicting data found in the literature. We assayed serum, platelet-rich, and platelet-poor plasma by two colorimetric endpoint methods and by an ultraviolet kinetic procedure. Platelet-poor plasma and serum had essentially the same activities by all three methods, whereas the activity in platelet-rich plasma plasma averaged fourfold that in platelet-poor plasma or serum when the assay was performed under conditions that result in lysis of platelets and release of their lactate dehydrogenase. When measurements were performed in platelet-rich plasma under conditions that prevented lysis of platelets, all three types of specimens gave the same results. This occurred when the osmolality of the reaction mixture was about 240 mOsm/kg of water. At an osmolality of about 120 mOsm, the activity of platelet-rich plasma was substantially lower than that of platelet-poor plasma or serum. If plasma must be used, the sample must first be centrifuged (3000 X g, 15 min) to provide a platelet-free plasma."} {"id": "PMID:1277500", "title": "Studies of the reliability of constituent target values established in a large inter-laboratory survey.", "content": "Lyophilized serum specimens were manufactured in such a way that fixed quantitative interspecimen relationships were established. The specimens were analyzed for about twenty constituents by several thousand laboratories in 1971, 1972, and 1973. Most of the consensus mean values derived from these analyses were found to relect accurately the relationships established in the manufacture of the specimens. In addition, analyses of some of the specimens for calcium by the National Bureau of Standards confirmed the relationships. I conclude that the consensus mean values derived for most constituents are reproducible and any biases that may be present are consistent from survey to survey.", "contents": "Studies of the reliability of constituent target values established in a large inter-laboratory survey. Lyophilized serum specimens were manufactured in such a way that fixed quantitative interspecimen relationships were established. The specimens were analyzed for about twenty constituents by several thousand laboratories in 1971, 1972, and 1973. Most of the consensus mean values derived from these analyses were found to relect accurately the relationships established in the manufacture of the specimens. In addition, analyses of some of the specimens for calcium by the National Bureau of Standards confirmed the relationships. I conclude that the consensus mean values derived for most constituents are reproducible and any biases that may be present are consistent from survey to survey."} {"id": "PMID:1277501", "title": "Derivatives of 1-naphthyl ethylenediamine dihydrochloride for standardization of direct-bilirubin assays done with the Technicon \"SMAC\".", "content": "The Jendrassik--Groff assay for direct bilirubin was adapted for analysis rates of 150/h on the Technicon \"SMAC\" continuous-flow analyzer. This requires development of a standard that is compatible with the other 19 channels on this analyzer. N-1-Naphthyl ethylenediamine dihydrochloride has been used for standardization of direct bilirubin assays, but we found it to be unsuitable because values for potassium are falsely elevated when potassium is determined with a valinomycin ion-selective electrode. This interference can be eliminated by alkylating the aliphatic amine group in the standard. The resulting compounds undergo the coupling reaction in the same way as the original compound and function equally well as standards for the direct bilirubin reaction. The only limitation of these analogs is their decreased solubility at physiological pH in some cases. Thus only certain alkyl groups are suitable.", "contents": "Derivatives of 1-naphthyl ethylenediamine dihydrochloride for standardization of direct-bilirubin assays done with the Technicon \"SMAC\". The Jendrassik--Groff assay for direct bilirubin was adapted for analysis rates of 150/h on the Technicon \"SMAC\" continuous-flow analyzer. This requires development of a standard that is compatible with the other 19 channels on this analyzer. N-1-Naphthyl ethylenediamine dihydrochloride has been used for standardization of direct bilirubin assays, but we found it to be unsuitable because values for potassium are falsely elevated when potassium is determined with a valinomycin ion-selective electrode. This interference can be eliminated by alkylating the aliphatic amine group in the standard. The resulting compounds undergo the coupling reaction in the same way as the original compound and function equally well as standards for the direct bilirubin reaction. The only limitation of these analogs is their decreased solubility at physiological pH in some cases. Thus only certain alkyl groups are suitable."} {"id": "PMID:1277502", "title": "Separation of folate binding protein from human serum by DEAE-cellulose column chromatography.", "content": "On diethylaminoethyl-cellulose column chromatography, the folate binding protein in the serum of 21 patients eluted in the early effluents as a single sharply defined peak. The chromatographic behavior of the folate binder remained unchanged whether or not the serum was, before chromatography, complexed with tritium-labeled pteroylglutamic acid ([3H]PGA), dialyzed, or charcoal-adsorbed. Heating to 100 degrees C for 10 min dissociated the [3H]PGA-binder complex while destroying the folate binding property. The presence or appearance of this folate binder in increased amounts in the serum of patients with various diseases may be related to conditions of increased tissue turnover.", "contents": "Separation of folate binding protein from human serum by DEAE-cellulose column chromatography. On diethylaminoethyl-cellulose column chromatography, the folate binding protein in the serum of 21 patients eluted in the early effluents as a single sharply defined peak. The chromatographic behavior of the folate binder remained unchanged whether or not the serum was, before chromatography, complexed with tritium-labeled pteroylglutamic acid ([3H]PGA), dialyzed, or charcoal-adsorbed. Heating to 100 degrees C for 10 min dissociated the [3H]PGA-binder complex while destroying the folate binding property. The presence or appearance of this folate binder in increased amounts in the serum of patients with various diseases may be related to conditions of increased tissue turnover."} {"id": "PMID:1277503", "title": "Methotrexate in blood, urine, and cerebrospinal fluid of children receiving high doses by infusion.", "content": "Methotrexate was determined in plasma (31 patients), urine (eight patients), and cerebrospinal fluid (two patients) after high doses (35 to 150 mg/kg) by infusion, with citrovorum factor rescue. Concentrations in plasma were proportional to dose at 6, 24, 72 h after beginning treatment, but this trend was very minimal for samples obtained at 48 h. Clinical toxicity probably will not be serious if the methotrexate concentration in the serum is less than 4.5 X 10(-6) mol/liter at 48 h after the start of a 6-h infusion. In both of the two patients so examined, therapeutic concentrations appeared in cerebrospinal fluid after intravenous infusion of the drug. A kinetic enzymic method, radioassay, and radioimmunoassay all yielded similar results for drug concentrations.", "contents": "Methotrexate in blood, urine, and cerebrospinal fluid of children receiving high doses by infusion. Methotrexate was determined in plasma (31 patients), urine (eight patients), and cerebrospinal fluid (two patients) after high doses (35 to 150 mg/kg) by infusion, with citrovorum factor rescue. Concentrations in plasma were proportional to dose at 6, 24, 72 h after beginning treatment, but this trend was very minimal for samples obtained at 48 h. Clinical toxicity probably will not be serious if the methotrexate concentration in the serum is less than 4.5 X 10(-6) mol/liter at 48 h after the start of a 6-h infusion. In both of the two patients so examined, therapeutic concentrations appeared in cerebrospinal fluid after intravenous infusion of the drug. A kinetic enzymic method, radioassay, and radioimmunoassay all yielded similar results for drug concentrations."} {"id": "PMID:1277504", "title": "Ultramicro gas-chromatographic analysis for anticonvulsants, with use of a nitrogen-selective detector.", "content": "We describe a procedure for determining phenobarbital, primidone, and diphenylhydantoin simultaneously in 50-mul volumes of serum by use of gas chromatography and a detector with heightened sensitivity and selectivity for nitrogenous compounds. The drugs, together with an internal standard, 5-allyl-5-phenyl barbituric acid, are extracted from serum by the procedure of MacGee [Anal. Chem. 42, 421 (1970)]. The drugs are converted to their methyl derivatives by a modification of the procedure of Greeley [Clin. Chem. 20, 192 (1974)] and then analyzed on a column containing 3% OV-1, with a temperature program, and detected by a nitrogen-selective detector. The method is reproducible to about 7%. Sensitivities of 0.5 mg/liter for 50-mul serum samples are attained routinely. Mephobarbital interferes with the analysis because methylation yields the same product as methylated phenobarbital. Total analysis time for a single sample is 15 min.", "contents": "Ultramicro gas-chromatographic analysis for anticonvulsants, with use of a nitrogen-selective detector. We describe a procedure for determining phenobarbital, primidone, and diphenylhydantoin simultaneously in 50-mul volumes of serum by use of gas chromatography and a detector with heightened sensitivity and selectivity for nitrogenous compounds. The drugs, together with an internal standard, 5-allyl-5-phenyl barbituric acid, are extracted from serum by the procedure of MacGee [Anal. Chem. 42, 421 (1970)]. The drugs are converted to their methyl derivatives by a modification of the procedure of Greeley [Clin. Chem. 20, 192 (1974)] and then analyzed on a column containing 3% OV-1, with a temperature program, and detected by a nitrogen-selective detector. The method is reproducible to about 7%. Sensitivities of 0.5 mg/liter for 50-mul serum samples are attained routinely. Mephobarbital interferes with the analysis because methylation yields the same product as methylated phenobarbital. Total analysis time for a single sample is 15 min."} {"id": "PMID:1277505", "title": "Simple determination of 3alpha-hydroxy fraction and 3beta-hydroxy fraction of urinary 17-ketosteroids.", "content": "We describe a method for determination of the 3alpha-hydroxysteroid fraction and 3beta-hydroxysteroid fraction of 17-ketosteroids in urine. The method includes enzymatic hydrolysis with beta-glucuronidase and extraction with ethyl acetate and color development of 3beta-hydroxysteroids by 3beta-hydroxysteroid oxidase and of total 17-ketosteroids by the Zimmermann reaction. The value for 3alpha-hydroxysteroids is calculated by subtracting the value for 3beta-hydroxysteroids from the value for total 17-ketosteroids. Recovery was assessed and results compared with those by an accepted method. Results were satisfactory for measuring these fractions of 17-ketosteroids.", "contents": "Simple determination of 3alpha-hydroxy fraction and 3beta-hydroxy fraction of urinary 17-ketosteroids. We describe a method for determination of the 3alpha-hydroxysteroid fraction and 3beta-hydroxysteroid fraction of 17-ketosteroids in urine. The method includes enzymatic hydrolysis with beta-glucuronidase and extraction with ethyl acetate and color development of 3beta-hydroxysteroids by 3beta-hydroxysteroid oxidase and of total 17-ketosteroids by the Zimmermann reaction. The value for 3alpha-hydroxysteroids is calculated by subtracting the value for 3beta-hydroxysteroids from the value for total 17-ketosteroids. Recovery was assessed and results compared with those by an accepted method. Results were satisfactory for measuring these fractions of 17-ketosteroids."} {"id": "PMID:1277506", "title": "Determination of carbamazepine in blood or plasma by high-pressure liquid chromatography.", "content": "We described a sensitive and precise high-pressure liquid-chromatographic method in which 5-(p-methylphenyl)-5-phenylhydantoin is used as the internal standard in determining carbamazepine in whole blood or plasma. Carbamazepine is well separated from normal blood constituents in less than 8 min, and other commonly used anticonvulsants do not interfere with the analysis. The sensitivity of this method is adequate to quantitate 0.25 mg of carbamazepine per liter in 2 ml of sample, and the lower limit of detection is 100 ng. Twenty specimens were analyzed by a gas-chromatographic method and by the present method; the resulting correlation coefficient was greater than .980.", "contents": "Determination of carbamazepine in blood or plasma by high-pressure liquid chromatography. We described a sensitive and precise high-pressure liquid-chromatographic method in which 5-(p-methylphenyl)-5-phenylhydantoin is used as the internal standard in determining carbamazepine in whole blood or plasma. Carbamazepine is well separated from normal blood constituents in less than 8 min, and other commonly used anticonvulsants do not interfere with the analysis. The sensitivity of this method is adequate to quantitate 0.25 mg of carbamazepine per liter in 2 ml of sample, and the lower limit of detection is 100 ng. Twenty specimens were analyzed by a gas-chromatographic method and by the present method; the resulting correlation coefficient was greater than .980."} {"id": "PMID:1277507", "title": "Equilibrium binding studies of insulin antibodies in diabetic subjects.", "content": "Equilibrium binding of insulin to human insulin antibodies from diabetic subjects has been studied by two methods. Results obtained by using a nondissociating gel filtration assay differed from those obtained by a conventional competitive binding method. Both methods yield data consistent with two classes of insulin binding site, having association constants of approximately 10(9) and 10(7) liter/mol. The principal differences are the higher association constant and lower number of binding sites for the high-affinity binding component, observed with the gel filtration method. In the conventional competitive binding assay, damaged radioligand, dissociation of the binding complex, or limitations of ligand availability may be responsible for the erroneous results. Data from nine diabetic patients indicate that insulin resistance and stability of diabetes cannot be explained by the binding properties of insulin antibodies alone.", "contents": "Equilibrium binding studies of insulin antibodies in diabetic subjects. Equilibrium binding of insulin to human insulin antibodies from diabetic subjects has been studied by two methods. Results obtained by using a nondissociating gel filtration assay differed from those obtained by a conventional competitive binding method. Both methods yield data consistent with two classes of insulin binding site, having association constants of approximately 10(9) and 10(7) liter/mol. The principal differences are the higher association constant and lower number of binding sites for the high-affinity binding component, observed with the gel filtration method. In the conventional competitive binding assay, damaged radioligand, dissociation of the binding complex, or limitations of ligand availability may be responsible for the erroneous results. Data from nine diabetic patients indicate that insulin resistance and stability of diabetes cannot be explained by the binding properties of insulin antibodies alone."} {"id": "PMID:1277508", "title": "Rate of decay and distribution volume of MB isoenzyme of creatine kinase, intravenously injected into the baboon.", "content": "We determined the decay constant and distribution space of the MB isoenzyme of creatine kinase after intravenous injection of 440 to 720 U, in a group of seven adult baboons. The rate of decay of the isoenzyme was monoexponential, with a mean decay constant of 0.00175 min-1 (SD, 0.00019). The mean distribution volume obtained by extrapolation of the monoexponential curve to zero time was 5.22% (SD, 1.06) of body weight. We have determined these parameters with the purpose of using this isoenzyme in the baboon as an experimental model for measuring myocardial infarct size.", "contents": "Rate of decay and distribution volume of MB isoenzyme of creatine kinase, intravenously injected into the baboon. We determined the decay constant and distribution space of the MB isoenzyme of creatine kinase after intravenous injection of 440 to 720 U, in a group of seven adult baboons. The rate of decay of the isoenzyme was monoexponential, with a mean decay constant of 0.00175 min-1 (SD, 0.00019). The mean distribution volume obtained by extrapolation of the monoexponential curve to zero time was 5.22% (SD, 1.06) of body weight. We have determined these parameters with the purpose of using this isoenzyme in the baboon as an experimental model for measuring myocardial infarct size."} {"id": "PMID:1277511", "title": "Direct use of ion-exchange papers in hemagglutination-inhibition tests for drug abuse.", "content": "I modified a procedure for screening urine specimens for evidence of drug abuse, to permit direct use of commercially available ion-exchange papers in hemagglutination-inhibition assay for drug detection. Small circles punched out of the papers, which previously had been impregnated with drug-containing urine, were used in the detection step, leaving the remainder of the specimens on paper available for confirmatory analyses. The procedure is useful in screening for the presence of opiates, methadone, and (or) barbiturates.", "contents": "Direct use of ion-exchange papers in hemagglutination-inhibition tests for drug abuse. I modified a procedure for screening urine specimens for evidence of drug abuse, to permit direct use of commercially available ion-exchange papers in hemagglutination-inhibition assay for drug detection. Small circles punched out of the papers, which previously had been impregnated with drug-containing urine, were used in the detection step, leaving the remainder of the specimens on paper available for confirmatory analyses. The procedure is useful in screening for the presence of opiates, methadone, and (or) barbiturates."} {"id": "PMID:1277512", "title": "Reduction of sample size on the Technicon SMA 6/60 continuous-flow analyzer.", "content": "The manifold of the Sequential Multiple Analyzer SMA 6/60 (4 + 2) has been modified to decrease serum sample size to 90 mul, by using a common diluent for all six channels and recycling the discard of each dialyzer into the next one. The modification can be made in less than 4 h without the need for any additional parts; the modified manifold requires one-third fewer pump lines and fewer reagents, thus reducing operating costs and simplifying instrument maintenance, while retaining the same precision, speed, low carryover, and linearity of the production model.", "contents": "Reduction of sample size on the Technicon SMA 6/60 continuous-flow analyzer. The manifold of the Sequential Multiple Analyzer SMA 6/60 (4 + 2) has been modified to decrease serum sample size to 90 mul, by using a common diluent for all six channels and recycling the discard of each dialyzer into the next one. The modification can be made in less than 4 h without the need for any additional parts; the modified manifold requires one-third fewer pump lines and fewer reagents, thus reducing operating costs and simplifying instrument maintenance, while retaining the same precision, speed, low carryover, and linearity of the production model."} {"id": "PMID:1277525", "title": "Ultramicromethod for determination of plasma uric acid.", "content": "We describe an ultramicromethod for determination of uric acid by a manual procedure. Hydrogen peroxide, formed when uric acid is oxidized in the presence of uricase, oxidatively couples two molecules of p-hydroxyphenylacetic acid in the presence of peroxidase to produce a highly fluorescent compound. The specificity of the uricase reaction is retained, and the fluorometry results in a higher sensitivity (but a lower precision) than that obtained by applying spectrophotometric methods. As little as 50 ng of uric acid can be determined, and only 10 mul of plasma is required. Values obtained for human plasma are higher than those obtained by the spectrophotometric method.", "contents": "Ultramicromethod for determination of plasma uric acid. We describe an ultramicromethod for determination of uric acid by a manual procedure. Hydrogen peroxide, formed when uric acid is oxidized in the presence of uricase, oxidatively couples two molecules of p-hydroxyphenylacetic acid in the presence of peroxidase to produce a highly fluorescent compound. The specificity of the uricase reaction is retained, and the fluorometry results in a higher sensitivity (but a lower precision) than that obtained by applying spectrophotometric methods. As little as 50 ng of uric acid can be determined, and only 10 mul of plasma is required. Values obtained for human plasma are higher than those obtained by the spectrophotometric method."} {"id": "PMID:1277526", "title": "Evaluation of benefits of screening tests done immediately on admission to hospital.", "content": "Evidence was sought of improved inpatient progress and reduced hospital costs when a battery of investigations were done at the time a patient was admitted to hospital. The outcome in 500 admission-tested patients was compared with that in two other groups of 500 control patients. No significant differences were found among the three groups in a variety of indices of inpatient progress. Because of an estimated 64% increase in the cost of investigating inpatients with admission testing, the total cost of hospital care was increased by about 5%. Under the conditions of this study, admission testing added to the cost of hospitalization, without associated evidence of benefit to the patient.", "contents": "Evaluation of benefits of screening tests done immediately on admission to hospital. Evidence was sought of improved inpatient progress and reduced hospital costs when a battery of investigations were done at the time a patient was admitted to hospital. The outcome in 500 admission-tested patients was compared with that in two other groups of 500 control patients. No significant differences were found among the three groups in a variety of indices of inpatient progress. Because of an estimated 64% increase in the cost of investigating inpatients with admission testing, the total cost of hospital care was increased by about 5%. Under the conditions of this study, admission testing added to the cost of hospitalization, without associated evidence of benefit to the patient."} {"id": "PMID:1277527", "title": "Alkaline phosphatase. II. Conditions affecting determination of total activity in serum.", "content": "Results of previous experiments on isolated purified isoenzymes of alkaline phosphatase from humans have been confirmed on sera containing relatively large activities of the different isoenzymes. The most remarkable finding is that activation by N-ethylaminoethanol is much more pronounced, in the case of the intestinal and placental isoenzymes, than is activation by diethanolamine. For several reasons, it is suggested that N-ethylaminoethanol is the buffer of choice, 0.1 mol/liter concentration for routine measurements and 1 mol/liter in those cases where the determination of the intestinal or placental isoenzymes is important. Mg2+ could be omitted because its addition increases the activity only marginally. Normal values for adults with use of 0.1 mol/liter N-ethylaminoethanol are 59 +/- 36 (2 SD) U/liter (n = 126).", "contents": "Alkaline phosphatase. II. Conditions affecting determination of total activity in serum. Results of previous experiments on isolated purified isoenzymes of alkaline phosphatase from humans have been confirmed on sera containing relatively large activities of the different isoenzymes. The most remarkable finding is that activation by N-ethylaminoethanol is much more pronounced, in the case of the intestinal and placental isoenzymes, than is activation by diethanolamine. For several reasons, it is suggested that N-ethylaminoethanol is the buffer of choice, 0.1 mol/liter concentration for routine measurements and 1 mol/liter in those cases where the determination of the intestinal or placental isoenzymes is important. Mg2+ could be omitted because its addition increases the activity only marginally. Normal values for adults with use of 0.1 mol/liter N-ethylaminoethanol are 59 +/- 36 (2 SD) U/liter (n = 126)."} {"id": "PMID:1277528", "title": "Analysis of variation in automated determination of sodium, potassium and calcium ions in human serum.", "content": "The concentration of sodium ion (Na+), potassium ion (K+) and calcium ion (Ca2+) in patient sera were assayed simultaneously on two separate flame photometers and then evaluated by analysis of variance (ANOVA). Two different experimental designs were devised in order to separate the error components assignable to pipetting, dilution, and instrumental measurement. Within-series variability was compared with the between-series variability. Similar statistical treatment of results from quality control samples gave estimates of variances between days, between dilutions, between instruments, and between channels, as well as the interaction terms and instrumental measurement errors. The total (overall) coefficients of variation (CV) were 1.15, 1.60, and 1.38% for Na+, K+, and Ca2+, respectively. The adequacy of the quality-control system to predict expected variation in patient specimens was verified by comparing errors from patient-sample duplicates and from control samples.", "contents": "Analysis of variation in automated determination of sodium, potassium and calcium ions in human serum. The concentration of sodium ion (Na+), potassium ion (K+) and calcium ion (Ca2+) in patient sera were assayed simultaneously on two separate flame photometers and then evaluated by analysis of variance (ANOVA). Two different experimental designs were devised in order to separate the error components assignable to pipetting, dilution, and instrumental measurement. Within-series variability was compared with the between-series variability. Similar statistical treatment of results from quality control samples gave estimates of variances between days, between dilutions, between instruments, and between channels, as well as the interaction terms and instrumental measurement errors. The total (overall) coefficients of variation (CV) were 1.15, 1.60, and 1.38% for Na+, K+, and Ca2+, respectively. The adequacy of the quality-control system to predict expected variation in patient specimens was verified by comparing errors from patient-sample duplicates and from control samples."} {"id": "PMID:1277535", "title": "A new rapid assay of oestrogens in pregnancy urine using the substrate native fluorescence.", "content": "A simple and rapid method is described for the quantitative determinations of free and conjugated oestrogens in pregnancy urine. The oestrogens are precipitated with ammonium sulphate and freed from non-oestrogenic compounds by solvent extraction. The conjugated oestrogens are hydrolysed by a beta-glucuronidase from Escherichia coli, and the total free oestrogens are extracted into ether and their fluorescence intensity at 310 nm in this solvent is determined. The method is rapid and precise for oestrogen levels at concentrations greater than 2 mug/ml (7 mumol/1). It is proposed that this method, which measures oestradiol and oestriol levels, be applied routinely to monitor feto-placental function in pregnancy. It offers advantages over other currently used assays in that less manipulative and technical skill is required to give a high level of precision and accuracy. An accurate estimate can be produced within 30-60 min of receipt of a 24-h uring specimen. Two variations of the method are also described. In one the ammonium sulphate precipitation step is omitted so as to give an even quicker assay procedure which determines conjugated oestrogens in the urine, and in the other oestriol only is determined.", "contents": "A new rapid assay of oestrogens in pregnancy urine using the substrate native fluorescence. A simple and rapid method is described for the quantitative determinations of free and conjugated oestrogens in pregnancy urine. The oestrogens are precipitated with ammonium sulphate and freed from non-oestrogenic compounds by solvent extraction. The conjugated oestrogens are hydrolysed by a beta-glucuronidase from Escherichia coli, and the total free oestrogens are extracted into ether and their fluorescence intensity at 310 nm in this solvent is determined. The method is rapid and precise for oestrogen levels at concentrations greater than 2 mug/ml (7 mumol/1). It is proposed that this method, which measures oestradiol and oestriol levels, be applied routinely to monitor feto-placental function in pregnancy. It offers advantages over other currently used assays in that less manipulative and technical skill is required to give a high level of precision and accuracy. An accurate estimate can be produced within 30-60 min of receipt of a 24-h uring specimen. Two variations of the method are also described. In one the ammonium sulphate precipitation step is omitted so as to give an even quicker assay procedure which determines conjugated oestrogens in the urine, and in the other oestriol only is determined."} {"id": "PMID:1277536", "title": "A novel specific assay of 25-hydroxy vitamin D.", "content": "The synthesis of 25-hydroxy-[26-2H3]vitamin D3 is described. A fixed amount of this compound (usually 250 ng) is added to a fixed amount of serum (usually 2.5 ml) and the mixture is extracted with a chloroform/methanol mixture. The extract is chromatographed on a Sephadex LH-20 column together with a trace amount of 25-hydroxy-[263H3]vitamin D3. The chromatographic fraction corresponding to 25-hydroxy vitamin D3 is converted into trimethylsilyl ether and the amount of unlabeled 25hydroxy vitamin D3 is determined from the ratio between the mass fragmentographic recording at m/e 131 (base peak of unlabeled 25-hydroxy vitamin D3) and m/e 134 (base peak 25-hydroxy-[26-2H3]vitamin D3). The relative standard deviation of the method was about 5%.", "contents": "A novel specific assay of 25-hydroxy vitamin D. The synthesis of 25-hydroxy-[26-2H3]vitamin D3 is described. A fixed amount of this compound (usually 250 ng) is added to a fixed amount of serum (usually 2.5 ml) and the mixture is extracted with a chloroform/methanol mixture. The extract is chromatographed on a Sephadex LH-20 column together with a trace amount of 25-hydroxy-[263H3]vitamin D3. The chromatographic fraction corresponding to 25-hydroxy vitamin D3 is converted into trimethylsilyl ether and the amount of unlabeled 25hydroxy vitamin D3 is determined from the ratio between the mass fragmentographic recording at m/e 131 (base peak of unlabeled 25-hydroxy vitamin D3) and m/e 134 (base peak 25-hydroxy-[26-2H3]vitamin D3). The relative standard deviation of the method was about 5%."} {"id": "PMID:1277537", "title": "Determination of plasma cholesterol: comparison of gas-liquid chromatographic, colorimetric and enzymatic analyses.", "content": "The efficacy of methods for plasma cholesterol analyses based on gas-liquid chromatographic (GLC) or enzymatic cholesterol determinations was tested on commercially available standard serum, plasma obtained in a study of an age stratum of the population and on plasma from a number of patients from an out-patient department. These results were compared with colorimetric cholesterol determinations on chloroform/methanol extracts from plasma using the ferric chloride/sulphuric acid reagent. The GLC-based procedure gave values 12% lower than the colorimetric determinations. This discrepancy seemed to be explained, to a marked extent, by the fact that cholesterol metabolites interfere with the colorimetric determinations. The GLC-based method was apparently accurate since it has the advantage of specificity and is easy to standardize with the internal standard technique. Enzymatic total cholesterol analyses gave slightly (2%) lower values than the GLC-based analyses, apparently because of an incomplete hydrolysis of cholesterol esters. Enzymatic analyses of free cholesterol gave similar results to those of the GLC-based method.", "contents": "Determination of plasma cholesterol: comparison of gas-liquid chromatographic, colorimetric and enzymatic analyses. The efficacy of methods for plasma cholesterol analyses based on gas-liquid chromatographic (GLC) or enzymatic cholesterol determinations was tested on commercially available standard serum, plasma obtained in a study of an age stratum of the population and on plasma from a number of patients from an out-patient department. These results were compared with colorimetric cholesterol determinations on chloroform/methanol extracts from plasma using the ferric chloride/sulphuric acid reagent. The GLC-based procedure gave values 12% lower than the colorimetric determinations. This discrepancy seemed to be explained, to a marked extent, by the fact that cholesterol metabolites interfere with the colorimetric determinations. The GLC-based method was apparently accurate since it has the advantage of specificity and is easy to standardize with the internal standard technique. Enzymatic total cholesterol analyses gave slightly (2%) lower values than the GLC-based analyses, apparently because of an incomplete hydrolysis of cholesterol esters. Enzymatic analyses of free cholesterol gave similar results to those of the GLC-based method."} {"id": "PMID:1277538", "title": "Abnormal serum lactate dehydrogenase isoenzyme in a case of laryngeal carcinoma and thyrotoxicosis.", "content": "An abnormal lactate dehydrogenase (LDH) isoenzyme was found in the serum of a patient with laryngeal carcinoma and hyperthyroidism. On electrophoresis it migrated as an additional band between LDH-1 and LDH-2. Follow-up studies suggested that this higher molecular weight, rather thermostable LDH isoenzyme, might have originated from the cancer tissue, though a possible relationship with the thyrotoxic state cannot be excluded.", "contents": "Abnormal serum lactate dehydrogenase isoenzyme in a case of laryngeal carcinoma and thyrotoxicosis. An abnormal lactate dehydrogenase (LDH) isoenzyme was found in the serum of a patient with laryngeal carcinoma and hyperthyroidism. On electrophoresis it migrated as an additional band between LDH-1 and LDH-2. Follow-up studies suggested that this higher molecular weight, rather thermostable LDH isoenzyme, might have originated from the cancer tissue, though a possible relationship with the thyrotoxic state cannot be excluded."} {"id": "PMID:1277539", "title": "Seasonal variation of urinary excretion of total metanephrines.", "content": "Results of 1414 measurements of urinary excretion of free and conjugated (total) metanephrine and normetanephrine (total metanephrines, tMN) and of 1630 measurements of vanilmandelic acid (VMA) excretion were analysed according to the month of sample collection. These collections had been carried out as a part of a study of hypertension at out institute over the 5-year period between 1970 and 1975. The means and scatters of tMN were significantly varied depending on the season of the year; the mean during 3 months of summer was 380 mug/day and the mean for 3 winter months 800 mug/day. The scatter of tMN in winter months was wider. A minor seasonal variation was observed for VMA: the means of summer and winter months were 3.8 mg/day and 4.5 mg/day, respectively. The results suggest a seasonal difference of catecholamine catabolism.", "contents": "Seasonal variation of urinary excretion of total metanephrines. Results of 1414 measurements of urinary excretion of free and conjugated (total) metanephrine and normetanephrine (total metanephrines, tMN) and of 1630 measurements of vanilmandelic acid (VMA) excretion were analysed according to the month of sample collection. These collections had been carried out as a part of a study of hypertension at out institute over the 5-year period between 1970 and 1975. The means and scatters of tMN were significantly varied depending on the season of the year; the mean during 3 months of summer was 380 mug/day and the mean for 3 winter months 800 mug/day. The scatter of tMN in winter months was wider. A minor seasonal variation was observed for VMA: the means of summer and winter months were 3.8 mg/day and 4.5 mg/day, respectively. The results suggest a seasonal difference of catecholamine catabolism."} {"id": "PMID:1277540", "title": "Molecular alterations in congenital erythrocyte pyruvate kinase deficiencies.", "content": "The molecular heterogeneity of congenital pyruvate kinase deficiencies becomes apparent from the results of immunological studies. In one case, a quantitative defect is plausible; in the second case, the most likely hypothesis is a molecular alteration of the binding site for the activator, with preservation of the antigenic specificity; in the third case an abnormal protein, extremely unstable and devoid of antigenic reactivity, carries catalytic activity. In no case can any cross-reacting material be detected.", "contents": "Molecular alterations in congenital erythrocyte pyruvate kinase deficiencies. The molecular heterogeneity of congenital pyruvate kinase deficiencies becomes apparent from the results of immunological studies. In one case, a quantitative defect is plausible; in the second case, the most likely hypothesis is a molecular alteration of the binding site for the activator, with preservation of the antigenic specificity; in the third case an abnormal protein, extremely unstable and devoid of antigenic reactivity, carries catalytic activity. In no case can any cross-reacting material be detected."} {"id": "PMID:1277541", "title": "Molecular sieving by glomerular basement membrane isolated from normal and nephrotic rabbits.", "content": "Analog chromatography with glomerular basement membrane isolated from normal and nephrotic rabbits was performed to see if there was a molecular sieving effect by the basement membrane. In a normal glomerular basement membrane column, 125I-labeled human serum globulin and 131I-labeled human serum albumin were eluted at the same position, probably at the void volume of the column. However, 125I-labeled insulin and tritiated water appeared with a delay and gave separated peaks. In nephrotic glomerular basement membrane, 125I-labeled human globulin, 131I-labeled serum albumin, 125I-labeled insulin and tritiated water gave four distinctly separated peaks in that order. By analogy with Sephadex, the sieving effect of glomerular basement membrane was demonstrated.", "contents": "Molecular sieving by glomerular basement membrane isolated from normal and nephrotic rabbits. Analog chromatography with glomerular basement membrane isolated from normal and nephrotic rabbits was performed to see if there was a molecular sieving effect by the basement membrane. In a normal glomerular basement membrane column, 125I-labeled human serum globulin and 131I-labeled human serum albumin were eluted at the same position, probably at the void volume of the column. However, 125I-labeled insulin and tritiated water appeared with a delay and gave separated peaks. In nephrotic glomerular basement membrane, 125I-labeled human globulin, 131I-labeled serum albumin, 125I-labeled insulin and tritiated water gave four distinctly separated peaks in that order. By analogy with Sephadex, the sieving effect of glomerular basement membrane was demonstrated."} {"id": "PMID:1277542", "title": "Glyceride content of amniotic fluid cells as an index of fetal maturity.", "content": "A simple biochemical method has been used to determine the content of neutral lipid of washed cell pellets prepared from 114 samples of amniotic fluid. This was done to improve the large standard deviation of the conventional orange fat cell measurements. By relating the content of neutral lipids to the total protein content of the pellet, the error of cell counting is minimized. The resultant glyceride/protein ratio increases 20 times within the last 8 weeks of pregnancy. The results are not altered by associated diabetes, hydramnios or Rh isoimmunization.", "contents": "Glyceride content of amniotic fluid cells as an index of fetal maturity. A simple biochemical method has been used to determine the content of neutral lipid of washed cell pellets prepared from 114 samples of amniotic fluid. This was done to improve the large standard deviation of the conventional orange fat cell measurements. By relating the content of neutral lipids to the total protein content of the pellet, the error of cell counting is minimized. The resultant glyceride/protein ratio increases 20 times within the last 8 weeks of pregnancy. The results are not altered by associated diabetes, hydramnios or Rh isoimmunization."} {"id": "PMID:1277545", "title": "Simple solid-phase radioimmunoassays for total tri-iodothyronine and thyroxine in serum, and their clinical evaluation.", "content": "1. Simple solid-phase radioimmunoassay methods for total tri-iodothyronine and thyroxine in serum or plasma are described. By using antibodies that are covalently coupled to microcrystalline cellulose, virtually identical assay procedures can be used for the determination of both hormones. An alkaline sodium glycinate buffer provides better assay conditions than the buffers often recommended for thyroid hormone radioimmunoassay. 2. Assay results are unaffected by moderate sample haemolysis. Plasma samples stored at room temperature for more than nine days often show an apparent increase in concentration of both thyroid hormones. 3. Serum tri-iodothyronine and thyroxine concentrations in healthy euthyroid subjects, and in euthyroid pregnant women are reported. In a series of 100 consecutive patients referred to a thyroid clinic the tri-iodothyronine assay discriminated better than the thyroxine assay between hyperthyroid and euthyroid patients. The thyroxine assay was much better than the tri-iodothyronine assay in discriminating between hypothyroid and euthyroid patients.", "contents": "Simple solid-phase radioimmunoassays for total tri-iodothyronine and thyroxine in serum, and their clinical evaluation. 1. Simple solid-phase radioimmunoassay methods for total tri-iodothyronine and thyroxine in serum or plasma are described. By using antibodies that are covalently coupled to microcrystalline cellulose, virtually identical assay procedures can be used for the determination of both hormones. An alkaline sodium glycinate buffer provides better assay conditions than the buffers often recommended for thyroid hormone radioimmunoassay. 2. Assay results are unaffected by moderate sample haemolysis. Plasma samples stored at room temperature for more than nine days often show an apparent increase in concentration of both thyroid hormones. 3. Serum tri-iodothyronine and thyroxine concentrations in healthy euthyroid subjects, and in euthyroid pregnant women are reported. In a series of 100 consecutive patients referred to a thyroid clinic the tri-iodothyronine assay discriminated better than the thyroxine assay between hyperthyroid and euthyroid patients. The thyroxine assay was much better than the tri-iodothyronine assay in discriminating between hypothyroid and euthyroid patients."} {"id": "PMID:1277546", "title": "Direct measurement of serum non-caeruloplasmin copper in liver disease.", "content": "The serum non-caeruloplasmin copper concentrations were measured in normal subjects and patients with various types of liver disease by a sensitive direct method involving complexing the copper and measurement by atomic absorption spectrophotometry. In normal subjects the mean concentration (+/- S.D.) was 10.1 +/- 1.6 mug/100 ml, males having a slightly higher value (10.7 +/- 1.3 mug/100 ml) than females (9.2 +/- 1.8 mug/100 ml). In patients with various non-hepatic diseases concentrations were raised (15.8 +/- 8.9 mug/100 ml), as also in hepatitis (14.7 +/- 4.3 mug/100 ml), cholestasis (16.1 +/- 6.4 mug/100 ml) and cirrhosis (16.3 +/- 8.7 mug/100 ml). Heterozygotes for Wilson's disease and patients treated for Wilson's disease had concentrations (12.9 +/- 5.9 and 9.8 +/- 3.7 mug/100 ml, respectively) which did not differ significantly from normal whereas untreated patients had very significantly raised concentrations (22.9 +/- 4.5 mug/100 ml). Direct measurement of serum non-caeruloplasmin copper is more accurate than indirect measurement and may help in assessing the effect of treatment but it is concluded that measurement of this fraction of serum copper will not enable Wilson's disease to be differentiated from other forms of liver disease.", "contents": "Direct measurement of serum non-caeruloplasmin copper in liver disease. The serum non-caeruloplasmin copper concentrations were measured in normal subjects and patients with various types of liver disease by a sensitive direct method involving complexing the copper and measurement by atomic absorption spectrophotometry. In normal subjects the mean concentration (+/- S.D.) was 10.1 +/- 1.6 mug/100 ml, males having a slightly higher value (10.7 +/- 1.3 mug/100 ml) than females (9.2 +/- 1.8 mug/100 ml). In patients with various non-hepatic diseases concentrations were raised (15.8 +/- 8.9 mug/100 ml), as also in hepatitis (14.7 +/- 4.3 mug/100 ml), cholestasis (16.1 +/- 6.4 mug/100 ml) and cirrhosis (16.3 +/- 8.7 mug/100 ml). Heterozygotes for Wilson's disease and patients treated for Wilson's disease had concentrations (12.9 +/- 5.9 and 9.8 +/- 3.7 mug/100 ml, respectively) which did not differ significantly from normal whereas untreated patients had very significantly raised concentrations (22.9 +/- 4.5 mug/100 ml). Direct measurement of serum non-caeruloplasmin copper is more accurate than indirect measurement and may help in assessing the effect of treatment but it is concluded that measurement of this fraction of serum copper will not enable Wilson's disease to be differentiated from other forms of liver disease."} {"id": "PMID:1277549", "title": "The relationship between serum creatine kinase and thyroid hormones: in vivo and in vitro studies.", "content": "Creatine kinase activity was measured in sera submitted for thyroid investigations. Although, as groups, hypothyroid and hyperthyroid subjects had higher and lower creatine kinase results than normal, the assay was not satisfactory as a screening test for predicting thyroid status in the individual. Attempts to inhibit the serum enzyme in vitro using high concentrations of thyroxine and tri-iodothyronine were unsuccessful. The inverse relation between serum creatine kinase and thyroid status is unlikely, therefore, to be due to a direct inhibitory effect of the hormones on the enzyme.", "contents": "The relationship between serum creatine kinase and thyroid hormones: in vivo and in vitro studies. Creatine kinase activity was measured in sera submitted for thyroid investigations. Although, as groups, hypothyroid and hyperthyroid subjects had higher and lower creatine kinase results than normal, the assay was not satisfactory as a screening test for predicting thyroid status in the individual. Attempts to inhibit the serum enzyme in vitro using high concentrations of thyroxine and tri-iodothyronine were unsuccessful. The inverse relation between serum creatine kinase and thyroid status is unlikely, therefore, to be due to a direct inhibitory effect of the hormones on the enzyme."} {"id": "PMID:1277553", "title": "Evaluation of the specificity of a luteinizing hormone beta and alpha subunit assay.", "content": "A non-specific antihuman FSH antiserum which is able to bind 125I-labelled FSH, LH, LHbeta and LHalpha subunits, has been shown to contain at least three different antibody populations directed against different parts of the LH and FSH molecule. This antiserum has been used to develop a rather specific radio-immunoassay for determination of the common alpha subunit. Further, by gel filtration it is shown that the LH IRC2/69 preparation contains about 30% of intact LH and about 10% of alpha and LHbeta subunit, respectively. In contrast, the LH 68/40 preparation contains about 96% of intact LH and only small amounts of alpha and LHbeta subunit. Also, a considerable difference in the content of the alpha sub-unit was found between two different FSH preparations. The contamination of the preparations of the intact hormones is shown to have a marked influence on the cross-reactivity of the substances in an LHbeta and alpha subunit radioimmuno-assay.", "contents": "Evaluation of the specificity of a luteinizing hormone beta and alpha subunit assay. A non-specific antihuman FSH antiserum which is able to bind 125I-labelled FSH, LH, LHbeta and LHalpha subunits, has been shown to contain at least three different antibody populations directed against different parts of the LH and FSH molecule. This antiserum has been used to develop a rather specific radio-immunoassay for determination of the common alpha subunit. Further, by gel filtration it is shown that the LH IRC2/69 preparation contains about 30% of intact LH and about 10% of alpha and LHbeta subunit, respectively. In contrast, the LH 68/40 preparation contains about 96% of intact LH and only small amounts of alpha and LHbeta subunit. Also, a considerable difference in the content of the alpha sub-unit was found between two different FSH preparations. The contamination of the preparations of the intact hormones is shown to have a marked influence on the cross-reactivity of the substances in an LHbeta and alpha subunit radioimmuno-assay."} {"id": "PMID:1277554", "title": "Isoelectrofocusing: a method of multiple applications for hemoglobin studies.", "content": "A microanalytical screening of hemoglobins by isoelectric focusing on acryl-amide gel columns is described. Addition of this technique to our regular analytical procedures revealed many mutants, praticularly some neutral ones which were not resolved by other conventional procedures. Extension of this technique to a quantitative scale permitted rapid isolation of some unstable mutants in an almost pure form ready for functional studies. The natural color of the separated components is often indicative of their nature and in cases like the sulfhemoglobin, Hbs M, they are of diagnostic value. The heme-losing, abnormal, unstable mutants, on the addition of external cyanhemin, take them up and change their isoelectric pH. This is an attractive visible procedure for their diagnosis. From all these results, it appears that isoelectric focusing as a single method brings more information than the other conventional procedures and hence can be considered as a semi-routine investigation for hemoglobin studies before deciding on a much longer procedure.", "contents": "Isoelectrofocusing: a method of multiple applications for hemoglobin studies. A microanalytical screening of hemoglobins by isoelectric focusing on acryl-amide gel columns is described. Addition of this technique to our regular analytical procedures revealed many mutants, praticularly some neutral ones which were not resolved by other conventional procedures. Extension of this technique to a quantitative scale permitted rapid isolation of some unstable mutants in an almost pure form ready for functional studies. The natural color of the separated components is often indicative of their nature and in cases like the sulfhemoglobin, Hbs M, they are of diagnostic value. The heme-losing, abnormal, unstable mutants, on the addition of external cyanhemin, take them up and change their isoelectric pH. This is an attractive visible procedure for their diagnosis. From all these results, it appears that isoelectric focusing as a single method brings more information than the other conventional procedures and hence can be considered as a semi-routine investigation for hemoglobin studies before deciding on a much longer procedure."} {"id": "PMID:1277556", "title": "Automated assay of ceruloplasmin by kinetic analysis of o-dianisidine oxidation.", "content": "Automated procedures for the kinetic assay of serum ceruloplasmin activity using a bichromatic and a centrifugal analyzer are described. The method is based on the oxidase activity of ceruloplasmin at pH 5.0 with o-dianisidine as substrate. Enzyme activity is reported in I.U./l, based on the molar absorption coefficient of o-dianisidine consumed. The substrate is stable and is not subject to non-enzymatic oxidation. Comparison with a manual reference end-point assay using the same substrate indicates good correlation of the bichromatic and centrifugal methods. The analytical precision is comparable to the manual assay for both methods.", "contents": "Automated assay of ceruloplasmin by kinetic analysis of o-dianisidine oxidation. Automated procedures for the kinetic assay of serum ceruloplasmin activity using a bichromatic and a centrifugal analyzer are described. The method is based on the oxidase activity of ceruloplasmin at pH 5.0 with o-dianisidine as substrate. Enzyme activity is reported in I.U./l, based on the molar absorption coefficient of o-dianisidine consumed. The substrate is stable and is not subject to non-enzymatic oxidation. Comparison with a manual reference end-point assay using the same substrate indicates good correlation of the bichromatic and centrifugal methods. The analytical precision is comparable to the manual assay for both methods."} {"id": "PMID:1277557", "title": "Simultaneous estimation of urinary steroids by semi-automated gas chromatography. Investigation of neo-natal infants and children with abnormal steroid synthesis.", "content": "Development of a method for multicomponent analysis of urinary steroids on open-tubular columns is described. The urinary steroid conjugates were hydrolysed enzymatically, extracted on Amberlite XAD-2 columns, purified on columns of Sephadex LH-20, then analysed as methyloxime trimethylsilyl ethers on a gas chromatograph on which up to 24 samples may be automatically injected. All major urinary steroids from 17-oxosteroids to cortisol metabolites were analysed and these were quantified relative to internal standards, 5alpha-androstane-3alpha, 17alpha-diol and cholesteryl butyrate added to the samples prior to derivatisation. The precision of the full technique and reproducibility of repetitive automatic solid injection was found to be acceptable for the purpose of profile analysis. Examples of urinary steroid profiles in normal infants and infants with disorders of adrenal steroid production and excretion are given.", "contents": "Simultaneous estimation of urinary steroids by semi-automated gas chromatography. Investigation of neo-natal infants and children with abnormal steroid synthesis. Development of a method for multicomponent analysis of urinary steroids on open-tubular columns is described. The urinary steroid conjugates were hydrolysed enzymatically, extracted on Amberlite XAD-2 columns, purified on columns of Sephadex LH-20, then analysed as methyloxime trimethylsilyl ethers on a gas chromatograph on which up to 24 samples may be automatically injected. All major urinary steroids from 17-oxosteroids to cortisol metabolites were analysed and these were quantified relative to internal standards, 5alpha-androstane-3alpha, 17alpha-diol and cholesteryl butyrate added to the samples prior to derivatisation. The precision of the full technique and reproducibility of repetitive automatic solid injection was found to be acceptable for the purpose of profile analysis. Examples of urinary steroid profiles in normal infants and infants with disorders of adrenal steroid production and excretion are given."} {"id": "PMID:1277558", "title": "An evaluation of three commercially prepared anion-exchange resin columns for separation of tetraiodothryonine in serum.", "content": "Three different commercially prepared anion-exchange resin columns for thyroxine (T4) separation from serum for the \"T4 by column\" assay were evaluated using the protocol of the supplier. The claims by the suppliers for the distribution and recovery of T4 in the first and second thyroxine-containing eluates were experimentally evaluated by the addition of a tracer quantity of purified [125I]T4. The average experimentally determined elution ratios of recoverable T4 (sum of T4 in first and second eluates) with these commercial columns were: Bio-Rad, 92.2:7.8 (90:10 claimed); Oxford, 87.8:12.2 (94:6 claimed); and Curtis Nuclear, 88.7:11.3 (80:20 claimed). The percent recoveries of T4 in the first thyroxine-containing eluate were: Oxford, 82.3 + 9.70 (x +/- 1 S.D.); Bio-Rad, 91.75 +/- 2.09; and Curtis Nuclear, 74.20 +/- 6.14. Mean serum T4 values obtained by the column method with all commercial columns tested were lower than competitive protein binding radio-assay (CPBR) values if the former values were not corrected for recovery. When individual recovery correction factors were applied to column results, improved correlation and better correspondence of \"T4 by column\" mean values with the CPBR values were noted. It is concluded that the largest part of the total variability of the \"T4 by column\" assay is contributed by the chromatographic step when the colorimetric step is performed with an automated technique.", "contents": "An evaluation of three commercially prepared anion-exchange resin columns for separation of tetraiodothryonine in serum. Three different commercially prepared anion-exchange resin columns for thyroxine (T4) separation from serum for the \"T4 by column\" assay were evaluated using the protocol of the supplier. The claims by the suppliers for the distribution and recovery of T4 in the first and second thyroxine-containing eluates were experimentally evaluated by the addition of a tracer quantity of purified [125I]T4. The average experimentally determined elution ratios of recoverable T4 (sum of T4 in first and second eluates) with these commercial columns were: Bio-Rad, 92.2:7.8 (90:10 claimed); Oxford, 87.8:12.2 (94:6 claimed); and Curtis Nuclear, 88.7:11.3 (80:20 claimed). The percent recoveries of T4 in the first thyroxine-containing eluate were: Oxford, 82.3 + 9.70 (x +/- 1 S.D.); Bio-Rad, 91.75 +/- 2.09; and Curtis Nuclear, 74.20 +/- 6.14. Mean serum T4 values obtained by the column method with all commercial columns tested were lower than competitive protein binding radio-assay (CPBR) values if the former values were not corrected for recovery. When individual recovery correction factors were applied to column results, improved correlation and better correspondence of \"T4 by column\" mean values with the CPBR values were noted. It is concluded that the largest part of the total variability of the \"T4 by column\" assay is contributed by the chromatographic step when the colorimetric step is performed with an automated technique."} {"id": "PMID:1277559", "title": "Semi-automated competitive protein binding analysis of serum thyroxine on reusable Sephadex columns and its advantages over radioimmunoassay.", "content": "Competitive protein-binding analysis of serum thyroxine on small, reusable, Sephadex columns has been further studied and improved. The improved, semi-automated procedure results in reduced working time and costs. It has also been established that triiodothyronine crossreacts only 1/6 to 1/9 as well as thyroxine, and can be ignored because it represents only about 1/80 of the total serum iodothyronine content. The economic and methodological advantages of the improved method over radioammunoassay and other displacement assays are discussed.", "contents": "Semi-automated competitive protein binding analysis of serum thyroxine on reusable Sephadex columns and its advantages over radioimmunoassay. Competitive protein-binding analysis of serum thyroxine on small, reusable, Sephadex columns has been further studied and improved. The improved, semi-automated procedure results in reduced working time and costs. It has also been established that triiodothyronine crossreacts only 1/6 to 1/9 as well as thyroxine, and can be ignored because it represents only about 1/80 of the total serum iodothyronine content. The economic and methodological advantages of the improved method over radioammunoassay and other displacement assays are discussed."} {"id": "PMID:1277561", "title": "A quantitation of lactate dehydrogenase non-linearity.", "content": "It was the objective of this study to quantitative the non-linearity seen in the lactate dehydrogenase reaction and relate these findings to the wide variation between reported values from various sources. Data are based upon two sample groupings: 1200 routine samples and 200 selected elevated specimens rangingg from 200 to 2000 I.U. (LD-L). This sample population demonstrated a rate of activity decrease rangin from 2% to 13% per minute, dependent upon activity level.", "contents": "A quantitation of lactate dehydrogenase non-linearity. It was the objective of this study to quantitative the non-linearity seen in the lactate dehydrogenase reaction and relate these findings to the wide variation between reported values from various sources. Data are based upon two sample groupings: 1200 routine samples and 200 selected elevated specimens rangingg from 200 to 2000 I.U. (LD-L). This sample population demonstrated a rate of activity decrease rangin from 2% to 13% per minute, dependent upon activity level."} {"id": "PMID:1277562", "title": "Metabolism of alpha-aminoadipic and alpha-ketoadipic acids: studies using rat and beef liver, and human leukocytes.", "content": "The reported studies have shown that alpha-DL-amino [1-14C]adipic acid is metabolized to radioactive alpha-ketoadipic acid and then to 14CO2 in rat and beef liver homogenates. It was also demonstrated that alpha-keto [1-14C]adipic acid is decarboxylated to 14CO2. The effects of several co-factors and other variables, i.e. alpha-ketoglutarate, pyridoxal phosphate, NAD, thiamine pyrophosphate (TPP), FAD, LA, and pH have also been delimited. These reactions and the effects of the co-factors were also established in freshly drawn leukocytes. Using the methods outlined, a technique for studying the metabolism of alpha-amino-adipate and alpha-ketoadipate in the leukocytes from 10 ml of blood was developed.", "contents": "Metabolism of alpha-aminoadipic and alpha-ketoadipic acids: studies using rat and beef liver, and human leukocytes. The reported studies have shown that alpha-DL-amino [1-14C]adipic acid is metabolized to radioactive alpha-ketoadipic acid and then to 14CO2 in rat and beef liver homogenates. It was also demonstrated that alpha-keto [1-14C]adipic acid is decarboxylated to 14CO2. The effects of several co-factors and other variables, i.e. alpha-ketoglutarate, pyridoxal phosphate, NAD, thiamine pyrophosphate (TPP), FAD, LA, and pH have also been delimited. These reactions and the effects of the co-factors were also established in freshly drawn leukocytes. Using the methods outlined, a technique for studying the metabolism of alpha-amino-adipate and alpha-ketoadipate in the leukocytes from 10 ml of blood was developed."} {"id": "PMID:1277563", "title": "The effects of therapy for mild hypertension on circulating level of dopamine beta-hydroxylase.", "content": "Circulating dopamine beta-hydroxylase levels and norepinephrine excretion were measured in 76 mild hypertensive patients. Levels of dopamine beta-hydroxylase, norepinephrine excretion and blood pressure were obtained both before and after the initiation of therapy. Data from 20 patients exhibiting a diastolic blood pressure decrease of 10 mmHg or more were compared with data from 10 normotensive individuals. Changes in dopamine beta-hydroxylase levels were similar for the two groups and were not related to blood pressure changes. Intra-individual variation was small in both groups. There were no detectable functional relationships between diastolic pressure and urinary norepinephrine, norepinephrine and dopamine beta-hydroxylase or dopamine beta-hydroxylase and diastolic pressure. It dose not seem likely that dopamine beta-hydroxylase levels can replace urinary catecholamines as a commonly used index of sympathetic activity.", "contents": "The effects of therapy for mild hypertension on circulating level of dopamine beta-hydroxylase. Circulating dopamine beta-hydroxylase levels and norepinephrine excretion were measured in 76 mild hypertensive patients. Levels of dopamine beta-hydroxylase, norepinephrine excretion and blood pressure were obtained both before and after the initiation of therapy. Data from 20 patients exhibiting a diastolic blood pressure decrease of 10 mmHg or more were compared with data from 10 normotensive individuals. Changes in dopamine beta-hydroxylase levels were similar for the two groups and were not related to blood pressure changes. Intra-individual variation was small in both groups. There were no detectable functional relationships between diastolic pressure and urinary norepinephrine, norepinephrine and dopamine beta-hydroxylase or dopamine beta-hydroxylase and diastolic pressure. It dose not seem likely that dopamine beta-hydroxylase levels can replace urinary catecholamines as a commonly used index of sympathetic activity."} {"id": "PMID:1277564", "title": "Membrane permeability in normal human lymphocytes and lymphocytes from patients with chronic lymphatic leukaemia.", "content": "The rate of release of intracellular enzymes from the lymphocytes of patients with chronic lymphatic leukaemia has been shown to be slower than that from normal lymphocytes, despite their lower enzyme contents. Addition of ATP, ADP and AMP to the medium reduces enzyme efflux in a manner similar to that in normal lymphocytes. Iodoacetate, however, causes a marked increase in enzyme leakage from both normal and leukaemic cells. It appears therefore that the membrane permeability of leukaemic lymphocytes is at least partly dependent upon the intracellular energy content. Since the ATP contents of the leukaemic cells were lower than those of normal lymphocytes, however, it is concluded that some additional factor is concerned in reducing permeability to enzymes in chronic lymphatic leukaemia. The possibility that the immunoglobulin associated with the cell membrane of leukaemic cells may play a part in reducing its permeability has been explored, but washed and unwashed cells were found to lose enzymes at similar rates. The lower permeability of the membranes of such cells may partly explain their longer lifespan in chronic lymphatic leukaemia.", "contents": "Membrane permeability in normal human lymphocytes and lymphocytes from patients with chronic lymphatic leukaemia. The rate of release of intracellular enzymes from the lymphocytes of patients with chronic lymphatic leukaemia has been shown to be slower than that from normal lymphocytes, despite their lower enzyme contents. Addition of ATP, ADP and AMP to the medium reduces enzyme efflux in a manner similar to that in normal lymphocytes. Iodoacetate, however, causes a marked increase in enzyme leakage from both normal and leukaemic cells. It appears therefore that the membrane permeability of leukaemic lymphocytes is at least partly dependent upon the intracellular energy content. Since the ATP contents of the leukaemic cells were lower than those of normal lymphocytes, however, it is concluded that some additional factor is concerned in reducing permeability to enzymes in chronic lymphatic leukaemia. The possibility that the immunoglobulin associated with the cell membrane of leukaemic cells may play a part in reducing its permeability has been explored, but washed and unwashed cells were found to lose enzymes at similar rates. The lower permeability of the membranes of such cells may partly explain their longer lifespan in chronic lymphatic leukaemia."} {"id": "PMID:1277568", "title": "A simple and rapid procedure for the preparation of human LDH-1 and LDH-5 using an ion-exchange mini-column.", "content": "A simple and rapid preparation of LDH-1 and LDH-5 from heart and liver homogenates is described. The preparation is carried out on a 3 ml mini-column of DEAE-Sephadex A-50. The fractions of heart homogenate containing LDH-1 were eluted with an NaCl gradient after salt elution of other isoenzymes. This semi-purified fraction was re-applied to a second column and the whole cycle was repeated. This procedure takes less than 90 min to complete and a 70% yield of LDH-1 can be obtained. The fractions of liver homogenate containing LDH-5 were eluted by simple washing of the gel column with Tris-HCl buffer. The semi-purified fraction was re-applied to a second column and the wash procedure was repeated. This preparation took less than 30 min to complete and a 70% yield was obtained. No apparatus other than a small mini-column is required for this purification.", "contents": "A simple and rapid procedure for the preparation of human LDH-1 and LDH-5 using an ion-exchange mini-column. A simple and rapid preparation of LDH-1 and LDH-5 from heart and liver homogenates is described. The preparation is carried out on a 3 ml mini-column of DEAE-Sephadex A-50. The fractions of heart homogenate containing LDH-1 were eluted with an NaCl gradient after salt elution of other isoenzymes. This semi-purified fraction was re-applied to a second column and the whole cycle was repeated. This procedure takes less than 90 min to complete and a 70% yield of LDH-1 can be obtained. The fractions of liver homogenate containing LDH-5 were eluted by simple washing of the gel column with Tris-HCl buffer. The semi-purified fraction was re-applied to a second column and the wash procedure was repeated. This preparation took less than 30 min to complete and a 70% yield was obtained. No apparatus other than a small mini-column is required for this purification."} {"id": "PMID:1277569", "title": "A new device for ultrafiltration. The ultrafiltrability of calcium and inorganic phosphate in human serum.", "content": "The various problems concerning the ultrafiltration of blood serum are outlined, and a novel ultrafiltration device, which overcomes all these problems is presented. Its main advantages are the following: (1) The deposition of protein on the filter is prevented by producing a flow across the filter surface. (2) The pCO2 remains constant, since the fluid is not in contact with a gas space. (3) The minimum serum volume is only 0.4 ml (4) Six samples can be processed simultaneously. (5) All commercially available filter types can be used. The machine, tested by measuring the ultrafiltrability of calcium, inorganic phosphate, sodium and chloride in human serum, proved to be a reliable laboratory tool. The precision of the determinations were comparable to respective serum analyses. The ultrafiltrabilities obtained, without correction for water content of serum, were 55.6 +/- 2.9% for calcium, 88.3 +/- 5.0% for inorganic phosphate, 95 +/- 1.7% for sodium, and 103 +/- 0.7% for chloride (means +/- S.D.).", "contents": "A new device for ultrafiltration. The ultrafiltrability of calcium and inorganic phosphate in human serum. The various problems concerning the ultrafiltration of blood serum are outlined, and a novel ultrafiltration device, which overcomes all these problems is presented. Its main advantages are the following: (1) The deposition of protein on the filter is prevented by producing a flow across the filter surface. (2) The pCO2 remains constant, since the fluid is not in contact with a gas space. (3) The minimum serum volume is only 0.4 ml (4) Six samples can be processed simultaneously. (5) All commercially available filter types can be used. The machine, tested by measuring the ultrafiltrability of calcium, inorganic phosphate, sodium and chloride in human serum, proved to be a reliable laboratory tool. The precision of the determinations were comparable to respective serum analyses. The ultrafiltrabilities obtained, without correction for water content of serum, were 55.6 +/- 2.9% for calcium, 88.3 +/- 5.0% for inorganic phosphate, 95 +/- 1.7% for sodium, and 103 +/- 0.7% for chloride (means +/- S.D.)."} {"id": "PMID:1277570", "title": "Specific 5alpha-dihydrotestosterone binding in labial skin fibroblasts cultured from patients.with male pseudohermaphroditism.", "content": "The cytoplasm of skin fibroblasts serially subcultured from the labium majus of normal human females binds 5alpha-dihydrotestosterone (5alpha-DHT) with high affinity and low capacity. Such binding was absent from the strains of two male pseudohermaphrodites with unambiguous female external genitalia: one of these was from a patient with the clinical features and a family history typical of complete testicular feminization; the other merited the same diagnosis on anatomic and endocrine grounds, but had an XYY karyotype in multiple tissues, including the testes. Normal cytoplasmic binding was found in strains from two prepubertal male pseudohermaphrodites with bilateral inguinal testes: one had unambiguous female external genitalia, the other had clitoromegaly; the former had normal specific nuclear binding of 5alpha-DHT, and thereby the target cell capacity for pubertal masculinization. Measurement of specific 5alpha-DHT binding by cultured labial skin fibroblasts should be an early step in the investigation of male pseudohermaphroditism with female external genitalia.", "contents": "Specific 5alpha-dihydrotestosterone binding in labial skin fibroblasts cultured from patients.with male pseudohermaphroditism. The cytoplasm of skin fibroblasts serially subcultured from the labium majus of normal human females binds 5alpha-dihydrotestosterone (5alpha-DHT) with high affinity and low capacity. Such binding was absent from the strains of two male pseudohermaphrodites with unambiguous female external genitalia: one of these was from a patient with the clinical features and a family history typical of complete testicular feminization; the other merited the same diagnosis on anatomic and endocrine grounds, but had an XYY karyotype in multiple tissues, including the testes. Normal cytoplasmic binding was found in strains from two prepubertal male pseudohermaphrodites with bilateral inguinal testes: one had unambiguous female external genitalia, the other had clitoromegaly; the former had normal specific nuclear binding of 5alpha-DHT, and thereby the target cell capacity for pubertal masculinization. Measurement of specific 5alpha-DHT binding by cultured labial skin fibroblasts should be an early step in the investigation of male pseudohermaphroditism with female external genitalia."} {"id": "PMID:1277571", "title": "Partial deletions and trisomies of chromosome 13; mapping of bands associated with particular malformations.", "content": "New techniques of human karyotyping have allowed us to define accurately the banding pattern of six new cases with partial duplication of deficiency of chromosome 13. It now seems possible to draw a rough map of chromosome 13, correlating observed malformations and phenotypic features with specific chromosome regions. Partial monosomy shows clinical features which are the antithesis of the corresponding trisomic phenotype (Lejeune 1966).", "contents": "Partial deletions and trisomies of chromosome 13; mapping of bands associated with particular malformations. New techniques of human karyotyping have allowed us to define accurately the banding pattern of six new cases with partial duplication of deficiency of chromosome 13. It now seems possible to draw a rough map of chromosome 13, correlating observed malformations and phenotypic features with specific chromosome regions. Partial monosomy shows clinical features which are the antithesis of the corresponding trisomic phenotype (Lejeune 1966)."} {"id": "PMID:1277573", "title": "The distribution of the third complement component and other polymorphic traits in rheumatoid arthritis.", "content": "The distribution of C'3 phenotypes in 61 seropositive rheumatoid arthritis patients and 464 normal blood donors in Tokyo was examined by high-voltage agarose gel electrophoresis. The allele of the common European variant, C3(F), is absent in Japanese, but another F allels, C3(Frare), is present with a frequency of 0.025 and 0.013 in RA patients and blood donors, respectively; the difference is not statistically significant. The distribution of phenotypes for several other enzyme systems was also determined in an attempt to detect association with RA Again, no statistically significant differences were found.", "contents": "The distribution of the third complement component and other polymorphic traits in rheumatoid arthritis. The distribution of C'3 phenotypes in 61 seropositive rheumatoid arthritis patients and 464 normal blood donors in Tokyo was examined by high-voltage agarose gel electrophoresis. The allele of the common European variant, C3(F), is absent in Japanese, but another F allels, C3(Frare), is present with a frequency of 0.025 and 0.013 in RA patients and blood donors, respectively; the difference is not statistically significant. The distribution of phenotypes for several other enzyme systems was also determined in an attempt to detect association with RA Again, no statistically significant differences were found."} {"id": "PMID:1277574", "title": "Mental retardation, malformation syndrome andpartial 7p monosomy [45, XX, tdic (7;15) (p21;p11)].", "content": "A mentally retarded and malformed girl is described. Her karyotype was 45,XX,tdic (7;15) (p21;p11), i.e. she was monosomic for bands 7p22 and a part of 7p21. Only one of the two centromeres of the dicentric chromosome appeared to be functioning. The C-band positive material was retained by both centromeres (or adjacent to them). However, the Cd-band positive structure was absent in the presumably nonfunctioning centromere region.", "contents": "Mental retardation, malformation syndrome andpartial 7p monosomy [45, XX, tdic (7;15) (p21;p11)]. A mentally retarded and malformed girl is described. Her karyotype was 45,XX,tdic (7;15) (p21;p11), i.e. she was monosomic for bands 7p22 and a part of 7p21. Only one of the two centromeres of the dicentric chromosome appeared to be functioning. The C-band positive material was retained by both centromeres (or adjacent to them). However, the Cd-band positive structure was absent in the presumably nonfunctioning centromere region."} {"id": "PMID:1277576", "title": "Familial partial trisomy 6q syndromes resulting from inherited ins (5;6) (q33;q15q27).", "content": "Two cases are reported of familial partial trisomy 6q syndrome due to segregation of ins(5;6) (q33;q15q27) in three generations. The common clinical features include growth and mental retardation, feeding difficulty during infancy, microcephaly with downward slanting palpebral fissures, flattened nasal bridge with anteverted and flared nares, long philtrum, high arched palate, partially opened and protruding mouth with receding chin, deep transverse creases of the ears, three creases on the 4th fingers, clinodactyly of the 5th fingers with a single crease, and other dermatoglyphic findings. These characteristic features of two patients appear to make partial trisomy 6q a clinically recognizable syndrome.", "contents": "Familial partial trisomy 6q syndromes resulting from inherited ins (5;6) (q33;q15q27). Two cases are reported of familial partial trisomy 6q syndrome due to segregation of ins(5;6) (q33;q15q27) in three generations. The common clinical features include growth and mental retardation, feeding difficulty during infancy, microcephaly with downward slanting palpebral fissures, flattened nasal bridge with anteverted and flared nares, long philtrum, high arched palate, partially opened and protruding mouth with receding chin, deep transverse creases of the ears, three creases on the 4th fingers, clinodactyly of the 5th fingers with a single crease, and other dermatoglyphic findings. These characteristic features of two patients appear to make partial trisomy 6q a clinically recognizable syndrome."} {"id": "PMID:1277577", "title": "Specific removal of DNA antibodies in vivo with an extracorporeal immuno-adsorbent.", "content": "The selective removal of circulating antibody specific for DNA was affected with an immuno-absorbent consisting of DNA-cellulose incorporated into agar gel. Antisera to DNA obtained from patient with systemic lupus erythematosus was circulated in vitro through experimental and control columns by a dual channel haemodialysis pump and serial aliquots were withdrawn and assayed for antibody. A 65% reduction in DNA binding of serum was achieved at a flow rate of 210 ml/min over a 4-hr period with no release of 125I-labelled DNA from the column into the serum. For in vivo studies, 2-6-3-8 kg rabbits were actively immunized with methylated bovine serum albumin conjugated to single-stranded DNA (MBSA-ssDNA). Whole blood was pumped from the femoral artery through an immuno-adsorbent composed of ssDNA-cellulose in an agar matrix. Results showed significant reductions in ssDNA binding activity over various periods after connection of the rabbit's circulation to the immuno-adsorbent with only minimal changes in BSA binding during the same period. Little release of incorporated 125I-labelled DNA from the column as assayed in the blood and tissues of the experimental animals occurred during the procedure. The immuno-adsorbent columns showed no residual cellular debris or thrombotic material. These results suggest that this immuno-adsorbent system may be used to specifically withdraw circulating DNA antibodies in vivo. Such a system may have clinical potential for specific therapy of systemic lupus erythematosus.", "contents": "Specific removal of DNA antibodies in vivo with an extracorporeal immuno-adsorbent. The selective removal of circulating antibody specific for DNA was affected with an immuno-absorbent consisting of DNA-cellulose incorporated into agar gel. Antisera to DNA obtained from patient with systemic lupus erythematosus was circulated in vitro through experimental and control columns by a dual channel haemodialysis pump and serial aliquots were withdrawn and assayed for antibody. A 65% reduction in DNA binding of serum was achieved at a flow rate of 210 ml/min over a 4-hr period with no release of 125I-labelled DNA from the column into the serum. For in vivo studies, 2-6-3-8 kg rabbits were actively immunized with methylated bovine serum albumin conjugated to single-stranded DNA (MBSA-ssDNA). Whole blood was pumped from the femoral artery through an immuno-adsorbent composed of ssDNA-cellulose in an agar matrix. Results showed significant reductions in ssDNA binding activity over various periods after connection of the rabbit's circulation to the immuno-adsorbent with only minimal changes in BSA binding during the same period. Little release of incorporated 125I-labelled DNA from the column as assayed in the blood and tissues of the experimental animals occurred during the procedure. The immuno-adsorbent columns showed no residual cellular debris or thrombotic material. These results suggest that this immuno-adsorbent system may be used to specifically withdraw circulating DNA antibodies in vivo. Such a system may have clinical potential for specific therapy of systemic lupus erythematosus."} {"id": "PMID:1277578", "title": "Cell-mediated immunity to gluten fraction III in adult coeliac disease.", "content": "Peripheral blood lymphocytes were obtained from twenty-seven healthy control subjects, twenty-one coeliac patients on a gluten-free diet and fourteen patients on a normal diet. When the cells were cultured in vitro in the presence of 2 and 4 mg of gluten fraction III, there were significant increases in the mean ratios of response for lymphocytes from gluten-free coeliacs compared to healthy controls after 4, 5 and 6 days of culture, but for those on a normal diet significant increases were found only when using 4 mg of gluten on the 4th and 5th days of culture. When three further patients were changed from a normal to a gluten-free diet, the ratios of response for their lymphocytes increased. The results suggest that certain coeliacs may exhibit a weak delayed hypersensitivity reaction to gluten. Its more ready demonstration in patients on a gluten-free diet could be explained on the release of sensitized lymphocytes from the intestinal mucosa into the peripheral circulation after gluten withdrawal.", "contents": "Cell-mediated immunity to gluten fraction III in adult coeliac disease. Peripheral blood lymphocytes were obtained from twenty-seven healthy control subjects, twenty-one coeliac patients on a gluten-free diet and fourteen patients on a normal diet. When the cells were cultured in vitro in the presence of 2 and 4 mg of gluten fraction III, there were significant increases in the mean ratios of response for lymphocytes from gluten-free coeliacs compared to healthy controls after 4, 5 and 6 days of culture, but for those on a normal diet significant increases were found only when using 4 mg of gluten on the 4th and 5th days of culture. When three further patients were changed from a normal to a gluten-free diet, the ratios of response for their lymphocytes increased. The results suggest that certain coeliacs may exhibit a weak delayed hypersensitivity reaction to gluten. Its more ready demonstration in patients on a gluten-free diet could be explained on the release of sensitized lymphocytes from the intestinal mucosa into the peripheral circulation after gluten withdrawal."} {"id": "PMID:1277579", "title": "Human sperm antigens and antisperm antibodies. III. Studies on acrosomal antigens.", "content": "Acrosome of human sperm possesses two distinct antigens that are immunogenic, and will elicit autoantibodies that are detectable by immunofluorescence (IF). The first antigen, Acl, diffuse in distribution, is probably glycoprotein in nature since it is removed by trypsin and periodate. It is readily removed from cells after incubation in acid buffer or phosphate-buffered saline (PBS), stable at 60 degrees C and not affected by trypsin inhibitor. The second antigen, Ac2, discrete in distribution, is resistant to trypsin treatment. It remains stable after incubation in acid buffer or PBS, is unstable at 60 degrees C and becomes more diffuse in distribution when incubated in acid buffer or trypsin inhibitor. The use of spermatozoa pretreated with acid buffer permits detection of anti-Ac2 antibody that coexists with anti-Ac1 antibody in the same serum sample. Both Ac1 and Ac2 antigens are demonstrable in spermatozoa from the ejaculate, epididymis and the testis; in spermatids and spermatocytes. Ac1 antigen appears to show extensive cross-reaction with micro-organisms and with antigen(s) of human adrenal gland; and anti-Ac1 antibody is found frequently in the serum of men before vasectomy. In contrast, Ac2 antigen does not show cross-reaction with micro-organisms or tissue antigens tested; and its antibody is found mainly in the male and primarily after vasectomy. Thus, anti-Ac2 antibody may be more indicative of an immune response to sperm, and should be sought in diseases related to sperm immunity.", "contents": "Human sperm antigens and antisperm antibodies. III. Studies on acrosomal antigens. Acrosome of human sperm possesses two distinct antigens that are immunogenic, and will elicit autoantibodies that are detectable by immunofluorescence (IF). The first antigen, Acl, diffuse in distribution, is probably glycoprotein in nature since it is removed by trypsin and periodate. It is readily removed from cells after incubation in acid buffer or phosphate-buffered saline (PBS), stable at 60 degrees C and not affected by trypsin inhibitor. The second antigen, Ac2, discrete in distribution, is resistant to trypsin treatment. It remains stable after incubation in acid buffer or PBS, is unstable at 60 degrees C and becomes more diffuse in distribution when incubated in acid buffer or trypsin inhibitor. The use of spermatozoa pretreated with acid buffer permits detection of anti-Ac2 antibody that coexists with anti-Ac1 antibody in the same serum sample. Both Ac1 and Ac2 antigens are demonstrable in spermatozoa from the ejaculate, epididymis and the testis; in spermatids and spermatocytes. Ac1 antigen appears to show extensive cross-reaction with micro-organisms and with antigen(s) of human adrenal gland; and anti-Ac1 antibody is found frequently in the serum of men before vasectomy. In contrast, Ac2 antigen does not show cross-reaction with micro-organisms or tissue antigens tested; and its antibody is found mainly in the male and primarily after vasectomy. Thus, anti-Ac2 antibody may be more indicative of an immune response to sperm, and should be sought in diseases related to sperm immunity."} {"id": "PMID:1277580", "title": "Cell-mediated immune response of patients with meningiomas defined in vitro by a [3H]proline microcytotoxicity test.", "content": "Cell-mediated cytotoxicity (CTX) of meningioma patients was assessed postoperatively by a [3H]proline microcytotoxicity test. Autologous and allogeneic tumour cells were used for prelabelling with isotope and peripheral blood lymphocytes added in a ratio of 200:1. After 60 hg the plates were washed and residual CMP counted. Control target cells consisted of normal skin fibroblasts. CTX was calculated in percentage reduction compared to cultures incubated with control lymphocytes. Specific CTX on meningioma cells (i.e. not destroying control cells) greater than 20% was considered 'positive' if significant at P less than 0-05. Fifteen of twenty-three meningiomas showed specific CTX (65%). Among eight CNS tumours of different type and thirteen non-malignant diseases and normals only three (14%) were specifically cytotoxic for meningioma cells. A cross-reaction could be demonstrated between autologous and allogeneic meningioma target cells. However, no activity of lymphocytes from patients with meningiomas on glioblastoma cells and foetal brain tissue could be found at the ratio used for evaluation. Evidence is presented indicating that a cellular immune response as measured in the microcytotoxic test may be dependent on a residual or recurrent tumour in the body.", "contents": "Cell-mediated immune response of patients with meningiomas defined in vitro by a [3H]proline microcytotoxicity test. Cell-mediated cytotoxicity (CTX) of meningioma patients was assessed postoperatively by a [3H]proline microcytotoxicity test. Autologous and allogeneic tumour cells were used for prelabelling with isotope and peripheral blood lymphocytes added in a ratio of 200:1. After 60 hg the plates were washed and residual CMP counted. Control target cells consisted of normal skin fibroblasts. CTX was calculated in percentage reduction compared to cultures incubated with control lymphocytes. Specific CTX on meningioma cells (i.e. not destroying control cells) greater than 20% was considered 'positive' if significant at P less than 0-05. Fifteen of twenty-three meningiomas showed specific CTX (65%). Among eight CNS tumours of different type and thirteen non-malignant diseases and normals only three (14%) were specifically cytotoxic for meningioma cells. A cross-reaction could be demonstrated between autologous and allogeneic meningioma target cells. However, no activity of lymphocytes from patients with meningiomas on glioblastoma cells and foetal brain tissue could be found at the ratio used for evaluation. Evidence is presented indicating that a cellular immune response as measured in the microcytotoxic test may be dependent on a residual or recurrent tumour in the body."} {"id": "PMID:1277581", "title": "Variations of blood lymphocytes during work studied by cell surface markers, DNA synthesis and cytotoxicity.", "content": "Highly purified peripheral blood lymphocytes from healthy individuals were obtained from samples collected before and after a standardized bicycle ergometer test. The physical activity resulted in a marked increase of circulating lymphocytes. The proportion of T lymphocytes estimated as cells forming rosettes with sheep red blood cells after incubation in the cold decreased, whereas a corresponding increase of cells with receptors for C3, IgG-Fc or surface immunoglobulin was noted. Moreover, after work an increase of cells simultaneously reacting with cell surface markers usually designed as T- or B-cell markers occurred. The reactivity of lymphocytes collected after work in response to Con A, PHA, PWM and PPD was impaired, whereas the slight response to LPS was unchanged. The K-cell cytotoxicity of lymphocytes collected after work increased. The data indicate that physical activity leads to the mobilization of lymphocytes from as yet undetermined sites and with changed composition and reactivity.", "contents": "Variations of blood lymphocytes during work studied by cell surface markers, DNA synthesis and cytotoxicity. Highly purified peripheral blood lymphocytes from healthy individuals were obtained from samples collected before and after a standardized bicycle ergometer test. The physical activity resulted in a marked increase of circulating lymphocytes. The proportion of T lymphocytes estimated as cells forming rosettes with sheep red blood cells after incubation in the cold decreased, whereas a corresponding increase of cells with receptors for C3, IgG-Fc or surface immunoglobulin was noted. Moreover, after work an increase of cells simultaneously reacting with cell surface markers usually designed as T- or B-cell markers occurred. The reactivity of lymphocytes collected after work in response to Con A, PHA, PWM and PPD was impaired, whereas the slight response to LPS was unchanged. The K-cell cytotoxicity of lymphocytes collected after work increased. The data indicate that physical activity leads to the mobilization of lymphocytes from as yet undetermined sites and with changed composition and reactivity."} {"id": "PMID:1277582", "title": "Time course studies on rat IgE production in N. Brasiliensis infection.", "content": "We present here a study of the relationship in time between the elevation of total serum IgE, the parasite-specific IgE response, and the potentiated IgE response to unrelated antigen which occurs in rats following infection with the worm parasite N. brasiliensis. During a first infection the potentiated IgE response (to egg albumin) and elevation of total IgE occur synchronously rising to a peak on days 12-14 after infection, with the fastest rate of increase occurring between days 8 and 10. N. brasiliensis-specific IgE rises to a peak some 2-3 weeks later when both total IgE and the potentiated response have largely declined. A strain difference is shown in that Wistar rats produce far lower levels of total and parasite-specific IgE than Hooded Listers. Events following reinfection differ in that total IgE rises more rapidly, very high levels being reached 6 days after reinfected together with a secondary specific IgE response to N. brasiliensis. The total IgE level, however, rises by a far greater factor than parasite-specific IgE and declines rapidly while the parasite-specific response declines slowly over many weeks. The egg albumin response is not repotentiated. It is proposed that the total IgE response and the potentiated IgE response which forms a small component of it results from the release of a non-specific IgE-stimulating factor produced by N. brasiliensis-specific T cells. In this scheme the same or similar cells are involved in the production of N. brasiliensis-specific IgE through a separate specific helper function.", "contents": "Time course studies on rat IgE production in N. Brasiliensis infection. We present here a study of the relationship in time between the elevation of total serum IgE, the parasite-specific IgE response, and the potentiated IgE response to unrelated antigen which occurs in rats following infection with the worm parasite N. brasiliensis. During a first infection the potentiated IgE response (to egg albumin) and elevation of total IgE occur synchronously rising to a peak on days 12-14 after infection, with the fastest rate of increase occurring between days 8 and 10. N. brasiliensis-specific IgE rises to a peak some 2-3 weeks later when both total IgE and the potentiated response have largely declined. A strain difference is shown in that Wistar rats produce far lower levels of total and parasite-specific IgE than Hooded Listers. Events following reinfection differ in that total IgE rises more rapidly, very high levels being reached 6 days after reinfected together with a secondary specific IgE response to N. brasiliensis. The total IgE level, however, rises by a far greater factor than parasite-specific IgE and declines rapidly while the parasite-specific response declines slowly over many weeks. The egg albumin response is not repotentiated. It is proposed that the total IgE response and the potentiated IgE response which forms a small component of it results from the release of a non-specific IgE-stimulating factor produced by N. brasiliensis-specific T cells. In this scheme the same or similar cells are involved in the production of N. brasiliensis-specific IgE through a separate specific helper function."} {"id": "PMID:1277583", "title": "Surface immunoglobulins of lymphocytes in plasmacytoma. V. The effect of RNA-rich extract from mouse plasmacytoma MOPC 104E on the immune response.", "content": "BALB/c mice with the plasmacytoma MOPC 104E producing monoclonal IgM-lambda with antibody activity to alpha-1,3 dextran were found to have B lymphocytes with surface immunoglobulins with the immunochemical characteristics of 104E IgM capable of binding alpha-1,3 dextran. RNA extracted from this plasmacytoma induced the synthesis of such surface immunoglobulins on normal B lymphocytes in vitro and in vivo. Injection of 200 mug of MOPC 104E RNA into normal mice 72 hr prior to the administration of the antigen kept the immune response to dextran-S intact, but suppressed that to other antigens, such as DNP-Ficoll and LPS, T cell-independent antigens, and SRBC and BSA which are T cell-dependent. The effect of the RNA was abolished by RNase but not by pronase and DNase. RNA extracted from LPC-1 tumour (gamma2a-k without known antibody activity) significantly suppressed the immune response to dextran-S and to other antigens in normal mice. Thus, opposite effects of MOPC 104E RNA on the response to specific and non-specific antigens strengthen the hypothesis that the immune deficiency in plasmacytoma bearing mice is due to the conversion of normal surface immunoglobulin of a population of B lymphocytes to the idiotype of the respective myeloma globulin.", "contents": "Surface immunoglobulins of lymphocytes in plasmacytoma. V. The effect of RNA-rich extract from mouse plasmacytoma MOPC 104E on the immune response. BALB/c mice with the plasmacytoma MOPC 104E producing monoclonal IgM-lambda with antibody activity to alpha-1,3 dextran were found to have B lymphocytes with surface immunoglobulins with the immunochemical characteristics of 104E IgM capable of binding alpha-1,3 dextran. RNA extracted from this plasmacytoma induced the synthesis of such surface immunoglobulins on normal B lymphocytes in vitro and in vivo. Injection of 200 mug of MOPC 104E RNA into normal mice 72 hr prior to the administration of the antigen kept the immune response to dextran-S intact, but suppressed that to other antigens, such as DNP-Ficoll and LPS, T cell-independent antigens, and SRBC and BSA which are T cell-dependent. The effect of the RNA was abolished by RNase but not by pronase and DNase. RNA extracted from LPC-1 tumour (gamma2a-k without known antibody activity) significantly suppressed the immune response to dextran-S and to other antigens in normal mice. Thus, opposite effects of MOPC 104E RNA on the response to specific and non-specific antigens strengthen the hypothesis that the immune deficiency in plasmacytoma bearing mice is due to the conversion of normal surface immunoglobulin of a population of B lymphocytes to the idiotype of the respective myeloma globulin."} {"id": "PMID:1277584", "title": "Autoimmune implications of vasectomy in man.", "content": "The frequent development of sperm antibodies following vasectomy does not appear to be related to the formation of other autoantibodies. We have examined serum taken from 346 men before and 6 months after vasectomy for seven different autoantibodies. The occurrence of positive results is comparable to any normal population.", "contents": "Autoimmune implications of vasectomy in man. The frequent development of sperm antibodies following vasectomy does not appear to be related to the formation of other autoantibodies. We have examined serum taken from 346 men before and 6 months after vasectomy for seven different autoantibodies. The occurrence of positive results is comparable to any normal population."} {"id": "PMID:1277585", "title": "Injurious effect on rat liver mitochondria by lymphocytes from patients with primary biliary cirrhosis.", "content": "Lymphocytes from primary biliary cirrhosis (PBC) patients were shown to have an injurious effect on rat liver mitochondria, as was demonstrated by the inhibition of mitochondrial respiratory control by these cells. The incubation of the PBC patients' lymphocytes with isolated rat liver mitochondria produced a significant inhibition of mitochondrial respiration in the presence of ADP. However, no significant effect on respiration was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis and miscellaneous liver diseases. The results suggest that this injurious effect of PBC lymphocytes on mitochondria might be a consequence of sensitization in vivo of the PBC patients' lymphocytes by the mitochondrial antigens.", "contents": "Injurious effect on rat liver mitochondria by lymphocytes from patients with primary biliary cirrhosis. Lymphocytes from primary biliary cirrhosis (PBC) patients were shown to have an injurious effect on rat liver mitochondria, as was demonstrated by the inhibition of mitochondrial respiratory control by these cells. The incubation of the PBC patients' lymphocytes with isolated rat liver mitochondria produced a significant inhibition of mitochondrial respiration in the presence of ADP. However, no significant effect on respiration was seen with control lymphocytes of normal persons or with lymphocytes from patients with alcoholic cirrhosis and miscellaneous liver diseases. The results suggest that this injurious effect of PBC lymphocytes on mitochondria might be a consequence of sensitization in vivo of the PBC patients' lymphocytes by the mitochondrial antigens."} {"id": "PMID:1277595", "title": "Determination of endogenous middle molecules in normal and uremic body fluids.", "content": "Methods have been developed which allow the separation and quantitation of middle molecules in biological fluids. The methods involve a newly developed high speed gel filtration technique (HSGF) combined with gradient ion exchange chromatography (GEC). The solutes were detected at 254 an 206 nm. The molecular weight range of the fractions isolated by HSGF was assessed with standards of known molecular weight. By the HSGF method normal and uremic plasma and urine were separted into 10 to 11 peaks based upon differences in molecular size. One of these peaks, no.7, which was present in uremic plasma but not detected in non-uremic plasma contained middle molecules (mol wt 1000-2000). Amino-acid analysis before and after acid hydrolysis showed this peak to contain a mixture of peptides. Using the GEC method peak 7 was further separated into 7-8 new peaks (7a,b,c, etc.). Plasma from six normal subjects and six non-uremic patients with various diseases yielded only two peaks, 7f and g, whereas urine from normal subjects, and plasma and urine from uremic patients contained all or most of these peaks. Amino-acid analysis of peak 7c, which was frequently found prominent in severly uremic patients indicates that it consists of a small peptide chain containing 8-10 amino acids.", "contents": "Determination of endogenous middle molecules in normal and uremic body fluids. Methods have been developed which allow the separation and quantitation of middle molecules in biological fluids. The methods involve a newly developed high speed gel filtration technique (HSGF) combined with gradient ion exchange chromatography (GEC). The solutes were detected at 254 an 206 nm. The molecular weight range of the fractions isolated by HSGF was assessed with standards of known molecular weight. By the HSGF method normal and uremic plasma and urine were separted into 10 to 11 peaks based upon differences in molecular size. One of these peaks, no.7, which was present in uremic plasma but not detected in non-uremic plasma contained middle molecules (mol wt 1000-2000). Amino-acid analysis before and after acid hydrolysis showed this peak to contain a mixture of peptides. Using the GEC method peak 7 was further separated into 7-8 new peaks (7a,b,c, etc.). Plasma from six normal subjects and six non-uremic patients with various diseases yielded only two peaks, 7f and g, whereas urine from normal subjects, and plasma and urine from uremic patients contained all or most of these peaks. Amino-acid analysis of peak 7c, which was frequently found prominent in severly uremic patients indicates that it consists of a small peptide chain containing 8-10 amino acids."} {"id": "PMID:1277597", "title": "Absence of glomerular renal tubular epithelial antigen in membranous glomerulonephritis.", "content": "Renal biopsies from 24 patients with membranous glomerulonephritis were examined by indirect immunofluorescence for the presence of autologous renal tubular epithelial antigen (RTE). Staining of the luminal layer of proximal tubular epithelium was found in all cases, as with normal human kidney, but granular staining along glomerular capillary walls was not observed. The role of RTE in the genesis of human membranous glomerulonephritis has not been confirmed.", "contents": "Absence of glomerular renal tubular epithelial antigen in membranous glomerulonephritis. Renal biopsies from 24 patients with membranous glomerulonephritis were examined by indirect immunofluorescence for the presence of autologous renal tubular epithelial antigen (RTE). Staining of the luminal layer of proximal tubular epithelium was found in all cases, as with normal human kidney, but granular staining along glomerular capillary walls was not observed. The role of RTE in the genesis of human membranous glomerulonephritis has not been confirmed."} {"id": "PMID:1277598", "title": "Clinical evaluation of an automated cleaning device for dialyzers.", "content": "This paper describes the clinical evaluation of dialyzer efficiency after cleaning and sterilization using an automated dialyzer cleaner. In vivo clearance measurements of small molecules and an in vitro measurement of BSP showed no diminution after 5 uses, and ultrafiltration rate did not decrease with an increase in dialyzer use. Scanning and transmission electron microscopy of the membrane showed an increase in accumulation of cellular debris and fibrin with increasing use. Our experience using the automated dialyzer clearner for more than one year leads us to conclude that it is an effective way to clean dialyzers and that no patient ill-health occurs as a result of re-using dialyzers cleaned by this technique.", "contents": "Clinical evaluation of an automated cleaning device for dialyzers. This paper describes the clinical evaluation of dialyzer efficiency after cleaning and sterilization using an automated dialyzer cleaner. In vivo clearance measurements of small molecules and an in vitro measurement of BSP showed no diminution after 5 uses, and ultrafiltration rate did not decrease with an increase in dialyzer use. Scanning and transmission electron microscopy of the membrane showed an increase in accumulation of cellular debris and fibrin with increasing use. Our experience using the automated dialyzer clearner for more than one year leads us to conclude that it is an effective way to clean dialyzers and that no patient ill-health occurs as a result of re-using dialyzers cleaned by this technique."} {"id": "PMID:1277599", "title": "Sodium polystyrene sulfonate resin candy for control of potassium in chronic dialysis patients.", "content": "A stable candy with 5.0 g sodium polystyrene sulfonate resin per piece was developed. In vitro testing indicated decrease in potassium concentration of 1.0 mEq per gram of resin. Six chronic dialysis patients with predialysis serum potassium of 5.2 mEq per liter or greater participated in a two week blind trial. No change in diet or dialysis routine was made during the study. Analysis of serum potassium by paired \"t\" test showed mean potassium decrease of 0.7 mEq per liter during treatment (P less than 0.001). Patient compliance and acceptance was excellent during the trial. Use in the treatment of chronic hyperkalemia may be worthwhile in the care of long-term dialysis patients.", "contents": "Sodium polystyrene sulfonate resin candy for control of potassium in chronic dialysis patients. A stable candy with 5.0 g sodium polystyrene sulfonate resin per piece was developed. In vitro testing indicated decrease in potassium concentration of 1.0 mEq per gram of resin. Six chronic dialysis patients with predialysis serum potassium of 5.2 mEq per liter or greater participated in a two week blind trial. No change in diet or dialysis routine was made during the study. Analysis of serum potassium by paired \"t\" test showed mean potassium decrease of 0.7 mEq per liter during treatment (P less than 0.001). Patient compliance and acceptance was excellent during the trial. Use in the treatment of chronic hyperkalemia may be worthwhile in the care of long-term dialysis patients."} {"id": "PMID:1277600", "title": "Development of renal scarring in an adult with recurrent urinary tract infection.", "content": "An adult patient is described with recurrent urinary tract infections who developed renal scarring while under observation. Intravenous urography (I.V.U.) and renal arteriography were performed during an initial attack of pyelonephritis and I.V.U.s were repeated at intervals during follow-up, when the patient was having recurrent infections. Over 2 years the right kidney size diminished from 10.5 to 7.0 cm, the cortex became irregular and calyceal clubbing occurred. During a further 2 years, when on regular treatment, attacks became less frequent but left-sided symptoms predominated. Repeat I.V.U. at the end of this period showed that the left kidney size had reduced from 12 to 10 cm, again with the development of cortical irregularity and calyceal clubbing. Biochemical evidence of renal impairment developed. At no time were obstruction, reflux or associated pathology demonstrated and there was no history of analgesic abuse. Recurrent infection is suggested as the etiology of the scarring.", "contents": "Development of renal scarring in an adult with recurrent urinary tract infection. An adult patient is described with recurrent urinary tract infections who developed renal scarring while under observation. Intravenous urography (I.V.U.) and renal arteriography were performed during an initial attack of pyelonephritis and I.V.U.s were repeated at intervals during follow-up, when the patient was having recurrent infections. Over 2 years the right kidney size diminished from 10.5 to 7.0 cm, the cortex became irregular and calyceal clubbing occurred. During a further 2 years, when on regular treatment, attacks became less frequent but left-sided symptoms predominated. Repeat I.V.U. at the end of this period showed that the left kidney size had reduced from 12 to 10 cm, again with the development of cortical irregularity and calyceal clubbing. Biochemical evidence of renal impairment developed. At no time were obstruction, reflux or associated pathology demonstrated and there was no history of analgesic abuse. Recurrent infection is suggested as the etiology of the scarring."} {"id": "PMID:1277601", "title": "An automated cleaning device for dialyzers: machine design and technology.", "content": "The expansion of dialysis services and the introduction of disposable dialyzers have led to an increase in cost of hemodialysis. Many centers have attempted to reduce the cost of dialysis by using dialyzers on multiple occasions after cleaning and sterilization. Manual techniques for cleaning dialyzers are tedious, using valuable technician time and possibly leading to an increase in exposure to Hepatitis B surface antigen. These disadvantages can be avoided by the use of the automated device in this paper. We have also evaluated the dependability of the machine and the reduction in dialysis costs realized from its use.", "contents": "An automated cleaning device for dialyzers: machine design and technology. The expansion of dialysis services and the introduction of disposable dialyzers have led to an increase in cost of hemodialysis. Many centers have attempted to reduce the cost of dialysis by using dialyzers on multiple occasions after cleaning and sterilization. Manual techniques for cleaning dialyzers are tedious, using valuable technician time and possibly leading to an increase in exposure to Hepatitis B surface antigen. These disadvantages can be avoided by the use of the automated device in this paper. We have also evaluated the dependability of the machine and the reduction in dialysis costs realized from its use."} {"id": "PMID:1277602", "title": "Techniques of EEG frequency analysis for evaluation of uremic encephalopathy.", "content": "In an effort to provide nephrologists with practical, objective, and quantitative methods for evaluating uremic encephalopathy and the severity of uremia, we investigated five techniques for EEG frequency analysis, the selection of EEG samples for analysis, and the normal values for dominant frequency and the percent of EEG power from one through six Hz. The five techniques consisted of 1. handcounting, 2. use of a tape recorder and sonic analysis system to determine EEG power versus frequency, 3. use of the tape recorder and sonic analysis system to determine EEG voltage versus frequency, 4. on-line measurement of % EEG voltage from one through six Hz, and 5. use of base line crossovers to count the number of waves occurring at each frequency. All techniques were found to be satisfactory. The most significant difference between techniques depended on whether wave amplitude influenced the analysis (techniques 2, 3, and 4) or did not (techniques 1 and 5); in the former case slow wave activity was more evident than in the latter case. Our experience indicated that the determination of relative EEG power from each frequency (EEG power versus frequency or power spectral density) was the most practical and revealing mode of analysis, but any of these techniques would be valid and useful if employed with awareness of the difference in the normal range obtained by different techniques.", "contents": "Techniques of EEG frequency analysis for evaluation of uremic encephalopathy. In an effort to provide nephrologists with practical, objective, and quantitative methods for evaluating uremic encephalopathy and the severity of uremia, we investigated five techniques for EEG frequency analysis, the selection of EEG samples for analysis, and the normal values for dominant frequency and the percent of EEG power from one through six Hz. The five techniques consisted of 1. handcounting, 2. use of a tape recorder and sonic analysis system to determine EEG power versus frequency, 3. use of the tape recorder and sonic analysis system to determine EEG voltage versus frequency, 4. on-line measurement of % EEG voltage from one through six Hz, and 5. use of base line crossovers to count the number of waves occurring at each frequency. All techniques were found to be satisfactory. The most significant difference between techniques depended on whether wave amplitude influenced the analysis (techniques 2, 3, and 4) or did not (techniques 1 and 5); in the former case slow wave activity was more evident than in the latter case. Our experience indicated that the determination of relative EEG power from each frequency (EEG power versus frequency or power spectral density) was the most practical and revealing mode of analysis, but any of these techniques would be valid and useful if employed with awareness of the difference in the normal range obtained by different techniques."} {"id": "PMID:1277611", "title": "Psychological aspects of chronic pelvic pain.", "content": "The patient with chronic pelvic pain represents a real challenge to the physician. The challenge is not primarily to relieve the pain, but to form a relationship with the patient and to try to learn about and help her with psychosocial distress. In this process the physician must use himself or herself as a human instrument to try to relieve suffering in the global aspect of the word.", "contents": "Psychological aspects of chronic pelvic pain. The patient with chronic pelvic pain represents a real challenge to the physician. The challenge is not primarily to relieve the pain, but to form a relationship with the patient and to try to learn about and help her with psychosocial distress. In this process the physician must use himself or herself as a human instrument to try to relieve suffering in the global aspect of the word."} {"id": "PMID:1277612", "title": "Psychophysiologic infertility: an overview.", "content": "It has been recognized for centuries that commotion in the mind very often is reflected in the functions of the body. A few years ago 50% of cases of infertility were classified as emotionally determined. Today only about 5% are so classified because the identification of defects in chemistry or physiology rules out the diagnosis. Many infertile women with physical defects have significant emotional disorders, and many infertile women with no demonstrable physical defect have no significant emotional disorders. The diagnosis of psychophysiologic infertility can be made only after identification of intrapsychic conflicts arising from cultural, environmental, or experiential factors that have modified function, chemistry, or structure. The gradual elucidation of the functions of the limbic system and more understanding of the roles of the neurotransmitter amines have led to the present understanding of the psychophysiology of infertility. It has been shown that the neurotransmitter amines influence the production of reproductive hormones and hormone-releasing factors. Many types of stress change the concentration, production, and modification of these transmitter compounds. Investigators have tried without success to identify specific emotional problems that eventually produce infertility. Infertile women do have more emotional disorders, however, and some seem to be cause-effect related. Infertility protects some women against significant psychic conflicts and becomes a defensive process. Removal of this defensive process without quieting the internal commotion can have deleterious effects. When one or both members of a marriage desire children, the identification of one as infertile puts a significant stress on the relationship. Interpersonal and intrapsychic turmoil results, which may require professional help to quiet. The treatment of psychophysiologic infertility should include identifying specific areas of conflict and then attempting to modify responses, attitudes, and affects that cause or intensify the conflicts. Through a learning experience, anxious and insecure patients can be helped to tolerate the anticipation of pregnancy and parenthood. Even those who do not achieve pregnancy can be helped to maintain their feelings of self-worth and self-esteem.", "contents": "Psychophysiologic infertility: an overview. It has been recognized for centuries that commotion in the mind very often is reflected in the functions of the body. A few years ago 50% of cases of infertility were classified as emotionally determined. Today only about 5% are so classified because the identification of defects in chemistry or physiology rules out the diagnosis. Many infertile women with physical defects have significant emotional disorders, and many infertile women with no demonstrable physical defect have no significant emotional disorders. The diagnosis of psychophysiologic infertility can be made only after identification of intrapsychic conflicts arising from cultural, environmental, or experiential factors that have modified function, chemistry, or structure. The gradual elucidation of the functions of the limbic system and more understanding of the roles of the neurotransmitter amines have led to the present understanding of the psychophysiology of infertility. It has been shown that the neurotransmitter amines influence the production of reproductive hormones and hormone-releasing factors. Many types of stress change the concentration, production, and modification of these transmitter compounds. Investigators have tried without success to identify specific emotional problems that eventually produce infertility. Infertile women do have more emotional disorders, however, and some seem to be cause-effect related. Infertility protects some women against significant psychic conflicts and becomes a defensive process. Removal of this defensive process without quieting the internal commotion can have deleterious effects. When one or both members of a marriage desire children, the identification of one as infertile puts a significant stress on the relationship. Interpersonal and intrapsychic turmoil results, which may require professional help to quiet. The treatment of psychophysiologic infertility should include identifying specific areas of conflict and then attempting to modify responses, attitudes, and affects that cause or intensify the conflicts. Through a learning experience, anxious and insecure patients can be helped to tolerate the anticipation of pregnancy and parenthood. Even those who do not achieve pregnancy can be helped to maintain their feelings of self-worth and self-esteem."} {"id": "PMID:1277627", "title": "Is scoliosis reversible? In Vivo observations of reversible morphological changes in the production of scoliosis in mice.", "content": "Without altering the osseous or muscular structure of Balb/c mice, the author was able to produce and reverse scoliotic deformation during the period of growth and development. Two series of investigations were performed, each involving extensive histological, morphological, and roentgenographic documentation: (1) control mice were maintained and sacrificed for examination at designated intervals and (2) experimental mice, whose right hind- and forequarters were surgically bound to allow only unilateral motion, were sacrificed and examined at corresponding intervals. The unilateral restriction of experimental animals were released at scheduled 5-day intervals during the 45-day period. These mice were then examined for restoration of normal histological and roentgenographic appearance. Changes in vertebral morphology were apparent after 35 days of restriction. Release at this time allowed restoration of normal vetebral appearance with the exception of a slight, measurable reduction in size. The results indicate that (1) limited activity retarded growth and (2) unilateral restriction caused geometrical variations (structural and morphological). Both of these alterations proved reversible once normal function (reciprocal motion) was restored to the murine spine.", "contents": "Is scoliosis reversible? In Vivo observations of reversible morphological changes in the production of scoliosis in mice. Without altering the osseous or muscular structure of Balb/c mice, the author was able to produce and reverse scoliotic deformation during the period of growth and development. Two series of investigations were performed, each involving extensive histological, morphological, and roentgenographic documentation: (1) control mice were maintained and sacrificed for examination at designated intervals and (2) experimental mice, whose right hind- and forequarters were surgically bound to allow only unilateral motion, were sacrificed and examined at corresponding intervals. The unilateral restriction of experimental animals were released at scheduled 5-day intervals during the 45-day period. These mice were then examined for restoration of normal histological and roentgenographic appearance. Changes in vertebral morphology were apparent after 35 days of restriction. Release at this time allowed restoration of normal vetebral appearance with the exception of a slight, measurable reduction in size. The results indicate that (1) limited activity retarded growth and (2) unilateral restriction caused geometrical variations (structural and morphological). Both of these alterations proved reversible once normal function (reciprocal motion) was restored to the murine spine."} {"id": "PMID:1277628", "title": "Fracture of a vertebral body end plate and disk protrusion causing subarachnoid block in an adolescent.", "content": "An apparently unique case of retroprotrusion of a portion of the vertebral end plate plus L4 disk in a 16-year-old boy demonstrated a complete myelographic block. The block was produced by a large fragment of bone which had broken off the inferior end plate of the body of L4 and was protruding into the spinal canal. Removal of the bony block and protruding disk resulted in complete resolution of symptoms.", "contents": "Fracture of a vertebral body end plate and disk protrusion causing subarachnoid block in an adolescent. An apparently unique case of retroprotrusion of a portion of the vertebral end plate plus L4 disk in a 16-year-old boy demonstrated a complete myelographic block. The block was produced by a large fragment of bone which had broken off the inferior end plate of the body of L4 and was protruding into the spinal canal. Removal of the bony block and protruding disk resulted in complete resolution of symptoms."} {"id": "PMID:1277629", "title": "The treatment of developmental coxa vara by abduction subtrochanteric and intertrochanteric femoral osteotomy with special reference to the role of adductor tenotomy.", "content": "Regardless of the method of fixation, results were good in 84.5 per cent of abduction trochanter osteotomies for developmental coxa vara in 32 hips. Operative treatment is recommended after 18 years of age. Inadequate correction occurred only in children in whom an adductor tenotomy had been omitted. Unsatisfactory correction was caused more frequently by faulty surgical technique than by bony remodelling. The latter was not seen after the age of 6 years.", "contents": "The treatment of developmental coxa vara by abduction subtrochanteric and intertrochanteric femoral osteotomy with special reference to the role of adductor tenotomy. Regardless of the method of fixation, results were good in 84.5 per cent of abduction trochanter osteotomies for developmental coxa vara in 32 hips. Operative treatment is recommended after 18 years of age. Inadequate correction occurred only in children in whom an adductor tenotomy had been omitted. Unsatisfactory correction was caused more frequently by faulty surgical technique than by bony remodelling. The latter was not seen after the age of 6 years."} {"id": "PMID:1277630", "title": "Traumatic coxa vera. A case report of spontaneous correction in a child.", "content": "Residual coxa vara is a common complication of femoral neck fracture in a child. Factors favoring the development of this complication are delayed reduction and avascular necrosis. The present case report is a 10-year follow-up of spontaneous correction of traumatic coxa vara in a child. This is of interest because residual coxa vara following a hip fracture in an adult is a deformity in which there is little if any corrective remodeling.", "contents": "Traumatic coxa vera. A case report of spontaneous correction in a child. Residual coxa vara is a common complication of femoral neck fracture in a child. Factors favoring the development of this complication are delayed reduction and avascular necrosis. The present case report is a 10-year follow-up of spontaneous correction of traumatic coxa vara in a child. This is of interest because residual coxa vara following a hip fracture in an adult is a deformity in which there is little if any corrective remodeling."} {"id": "PMID:1277631", "title": "Traumatic anterior dislocation of hip joint with vascular damage.", "content": "Closed reduction of an anterior dislocation of the hip joint in a 15-year-old boy failed because of interposition of capsule, iliopsoas and rectus femoris muscles. The immediate complications were compression of the common femoral artery, tear of the femoral vein, and fat embolism 24 hours after the injury. The sequelae were periarticular ossification and avascular necrosis of the femoral head. The definitive treatment was a Charnley total hip arthroplasty.", "contents": "Traumatic anterior dislocation of hip joint with vascular damage. Closed reduction of an anterior dislocation of the hip joint in a 15-year-old boy failed because of interposition of capsule, iliopsoas and rectus femoris muscles. The immediate complications were compression of the common femoral artery, tear of the femoral vein, and fat embolism 24 hours after the injury. The sequelae were periarticular ossification and avascular necrosis of the femoral head. The definitive treatment was a Charnley total hip arthroplasty."} {"id": "PMID:1277632", "title": "A case of cerivco-thoracic anomaly simulating traumatic fracture-dislocation.", "content": "A patient who sustained severe head trauma had a simulated C7, T1 fracture dislocation. Anteroposterior tomography of the cervico-thoracic junction disclosed anomalous vertebral-costal articulations. The rotation of the spine and the abnormal posterior articulations were secondary to anterior costal bridging. Tomography of the costo-vertebral facets in patients with unusual rib configurations may help delineate cases of thoracic spine rotation.", "contents": "A case of cerivco-thoracic anomaly simulating traumatic fracture-dislocation. A patient who sustained severe head trauma had a simulated C7, T1 fracture dislocation. Anteroposterior tomography of the cervico-thoracic junction disclosed anomalous vertebral-costal articulations. The rotation of the spine and the abnormal posterior articulations were secondary to anterior costal bridging. Tomography of the costo-vertebral facets in patients with unusual rib configurations may help delineate cases of thoracic spine rotation."} {"id": "PMID:1277633", "title": "Surgery of the clavicle in Sprengle's deformity.", "content": "Surgery for Sprengel's deformity can produce less lowering of the scapula than desired and occasionally can result in an injury to the brachial plexus or brachial artery. The method used to produce better correction and to avoid complications was a softening of a clavicle by the morcellization technique of Robinson et al. We feel that the procedure is a simple one which helps to improve the degree of correction and to avoid neurovascular complications. The procedure should be combined with the Woodward correction for Sprengel's deformity.", "contents": "Surgery of the clavicle in Sprengle's deformity. Surgery for Sprengel's deformity can produce less lowering of the scapula than desired and occasionally can result in an injury to the brachial plexus or brachial artery. The method used to produce better correction and to avoid complications was a softening of a clavicle by the morcellization technique of Robinson et al. We feel that the procedure is a simple one which helps to improve the degree of correction and to avoid neurovascular complications. The procedure should be combined with the Woodward correction for Sprengel's deformity."} {"id": "PMID:1277634", "title": "The influence of age on the results of open sternomastoid tenotomy in muscular torticollis.", "content": "The ideal age for surgery for muscular torticollis, the complications and results of open sternomastoid tenotomy were investigated in 60 patients operated on at different age-groups. Under the age of 1, tethering of the scar to the deeper structures was common and was mainly responsible for the lower percentage of good results (42.1 per cent). In the age-group 1 to 4 years, satisfactory correction of facial asymmetry, head and tilt and limitation of neck movements, was achieved with overall 66.7 per cent good results. However, in patients above the age of 5, not only was the correction of the secondary deformities uncertain but the late complications like loss of sternomastoid column, disfiguring scar and presence of lateral bands were more common. Only 33.3 per cent had good results in the 5 to 8 year age-group and none in the above 9 years age-group. The best time for surgery in muscular torticollis is in the patient between 1 and 4 years of age.", "contents": "The influence of age on the results of open sternomastoid tenotomy in muscular torticollis. The ideal age for surgery for muscular torticollis, the complications and results of open sternomastoid tenotomy were investigated in 60 patients operated on at different age-groups. Under the age of 1, tethering of the scar to the deeper structures was common and was mainly responsible for the lower percentage of good results (42.1 per cent). In the age-group 1 to 4 years, satisfactory correction of facial asymmetry, head and tilt and limitation of neck movements, was achieved with overall 66.7 per cent good results. However, in patients above the age of 5, not only was the correction of the secondary deformities uncertain but the late complications like loss of sternomastoid column, disfiguring scar and presence of lateral bands were more common. Only 33.3 per cent had good results in the 5 to 8 year age-group and none in the above 9 years age-group. The best time for surgery in muscular torticollis is in the patient between 1 and 4 years of age."} {"id": "PMID:1277635", "title": "The upper limb-cardiovascular syndrome, (Holt-Oram syndrome).", "content": "Two families recently studied demonstrate the variability of expression of upper limb-cardiovascular syndrome. Four other patients with upper limb and cardiac anomalies and no significant family history may represent spontaneous mutations or examples impenetrance in antecedent generations, rather than phenocopies of the syndrome. Children under the care of the orthopedist for congenital anomalies of the upper limb should have a complete cardiac assessment.", "contents": "The upper limb-cardiovascular syndrome, (Holt-Oram syndrome). Two families recently studied demonstrate the variability of expression of upper limb-cardiovascular syndrome. Four other patients with upper limb and cardiac anomalies and no significant family history may represent spontaneous mutations or examples impenetrance in antecedent generations, rather than phenocopies of the syndrome. Children under the care of the orthopedist for congenital anomalies of the upper limb should have a complete cardiac assessment."} {"id": "PMID:1277636", "title": "A valgus angulation fracture of the proximal humeral epiphysis.", "content": "The case presented illustrates a previously unreported form of valgus angulation of a proximal humeral epiphyseal fracture. For reduction this fracture requires traction and adduction, not abduction, of the arm.", "contents": "A valgus angulation fracture of the proximal humeral epiphysis. The case presented illustrates a previously unreported form of valgus angulation of a proximal humeral epiphyseal fracture. For reduction this fracture requires traction and adduction, not abduction, of the arm."} {"id": "PMID:1277637", "title": "Osteoid osteoma of the trapezium. First case report of roentgenographically demonstrated progression in the trapezium.", "content": "Osteoid osteoma in the trapezium seems not to have been reported previously. This occurred in a 16-year-old boy who had complete and instant relief of pain following excision. There was progression of the lesion from roentgenographically normal appearing bone to bone with typical changes of osteoid osteoma.", "contents": "Osteoid osteoma of the trapezium. First case report of roentgenographically demonstrated progression in the trapezium. Osteoid osteoma in the trapezium seems not to have been reported previously. This occurred in a 16-year-old boy who had complete and instant relief of pain following excision. There was progression of the lesion from roentgenographically normal appearing bone to bone with typical changes of osteoid osteoma."} {"id": "PMID:1277638", "title": "Congenital flexion and ulnar deviation of the metacarpophalangeal joints of the hand. A case report.", "content": "A 2-year-old boy with congenital ulnar deviation and flexion deformity of the metacarpophalangeal joints (incidentally associated with ipsilateral metatarsus varus) was treated by surgical centralization of the extensor tendons. The operation improved function. Early splintage in infancy may avoid the need for surgical treatment in many cases.", "contents": "Congenital flexion and ulnar deviation of the metacarpophalangeal joints of the hand. A case report. A 2-year-old boy with congenital ulnar deviation and flexion deformity of the metacarpophalangeal joints (incidentally associated with ipsilateral metatarsus varus) was treated by surgical centralization of the extensor tendons. The operation improved function. Early splintage in infancy may avoid the need for surgical treatment in many cases."} {"id": "PMID:1277639", "title": "Open reduction of fractures of the neck of the proximal phalanx in children.", "content": "Fractures through phalangeal necks of proximal phalanges in children, which are angled so as to produce a dislocation or subluxation at the next distal joint, require open reduction. The technique includes a zigzag incision, a splitting of the extensor tendon, and the use of crossed Kirschner wires of .035 mm. Infections have not occurred from allowing the wires to protrude through the skin. The end results are better than those reported from conservative management of this fracture. The earlier the surgery the better the end results.", "contents": "Open reduction of fractures of the neck of the proximal phalanx in children. Fractures through phalangeal necks of proximal phalanges in children, which are angled so as to produce a dislocation or subluxation at the next distal joint, require open reduction. The technique includes a zigzag incision, a splitting of the extensor tendon, and the use of crossed Kirschner wires of .035 mm. Infections have not occurred from allowing the wires to protrude through the skin. The end results are better than those reported from conservative management of this fracture. The earlier the surgery the better the end results."} {"id": "PMID:1277640", "title": "Osgood-Schlatter's disease and tibial tuberosity development.", "content": "The growth plate of the tibial tuberosity does not develop until several months after birth and is structurally different than most growth plates that are loaded primarily in compression. Histologically, it is particularly different from the juxtaposed proximal tibial growth plate. The physis of the tibial tuberosity is composed primarily of fibrocartilage and fibrous tissue, with bone being added to the anterior portion of the tibial metaphysis by membranous bone formation. Initially very little of the growth plate is comprised of columnated cells, but by the time of maturation of the tuberosity, with the exception being the most distal region, the columnar portion has extended distally and is found under most of the tuberosity. These structural features would be an adaptation to the strong tensile forces exerted in this region. That human \"traction\" apophyses may be histologically different from \"compression\" epiphyses seems not to have been demonstrated previously. Osgood-Schlatter's disease would appear to be an inability of the developing secondary ossification center to withstand tensile forces, resulting in avulsion of segments of the ossification center, and eventual formation of extra bone(s) between the fragments.", "contents": "Osgood-Schlatter's disease and tibial tuberosity development. The growth plate of the tibial tuberosity does not develop until several months after birth and is structurally different than most growth plates that are loaded primarily in compression. Histologically, it is particularly different from the juxtaposed proximal tibial growth plate. The physis of the tibial tuberosity is composed primarily of fibrocartilage and fibrous tissue, with bone being added to the anterior portion of the tibial metaphysis by membranous bone formation. Initially very little of the growth plate is comprised of columnated cells, but by the time of maturation of the tuberosity, with the exception being the most distal region, the columnar portion has extended distally and is found under most of the tuberosity. These structural features would be an adaptation to the strong tensile forces exerted in this region. That human \"traction\" apophyses may be histologically different from \"compression\" epiphyses seems not to have been demonstrated previously. Osgood-Schlatter's disease would appear to be an inability of the developing secondary ossification center to withstand tensile forces, resulting in avulsion of segments of the ossification center, and eventual formation of extra bone(s) between the fragments."} {"id": "PMID:1277641", "title": "The accessory soleus muscle.", "content": "This is a report on the EMG diagnosis and surgical treatment of a tumor-like mass in the ankle of a 13-year-old boy with an accessory soleus muscle.", "contents": "The accessory soleus muscle. This is a report on the EMG diagnosis and surgical treatment of a tumor-like mass in the ankle of a 13-year-old boy with an accessory soleus muscle."} {"id": "PMID:1277642", "title": "Ewing's sarcoma of the great toe. A case report.", "content": "A case of Ewing's Sarcoma originating the great toe is reported. Because of the rarity of its appearance outside the pelvis and long tubular bones, Ewing's Sarcoma is often misdiagnosed when it occurs in the distal portion of the extremities. Ewing's Sarcoma may be difficult to distinguish from infection. Biopsy is recommended for any indolent or refractory lesions presumed to be infectious. Bone scanning with Technetium Polyphosphate is a useful tool for diagnosis and evaluation of this tumor. Vigorous integrated chemotherapy and radiotherapy had little effect in this patient with metastatic disease.", "contents": "Ewing's sarcoma of the great toe. A case report. A case of Ewing's Sarcoma originating the great toe is reported. Because of the rarity of its appearance outside the pelvis and long tubular bones, Ewing's Sarcoma is often misdiagnosed when it occurs in the distal portion of the extremities. Ewing's Sarcoma may be difficult to distinguish from infection. Biopsy is recommended for any indolent or refractory lesions presumed to be infectious. Bone scanning with Technetium Polyphosphate is a useful tool for diagnosis and evaluation of this tumor. Vigorous integrated chemotherapy and radiotherapy had little effect in this patient with metastatic disease."} {"id": "PMID:1277643", "title": "The development of a total wrist arthroplasty.", "content": "For many individuals the preservation of wrist motion is essential for augmentation of fine motor control of the hand and fingers. When significant functional disability exists at the wrist, currently available surgical treatment includes soft tissue arthroplasty, carpectomy, or arthrodesis. A total wrist joint arthroplasty offers the patient the potential of a pain-free, stable, and mobile wrist. Based upon the principles of total joint replacement as applied to the hip and knee, the prosthesis is secured to the carpus and radius with methylmethacrylate cement, following removal of the navicular, lunate, and head of the capitate. The design of the prosthesis provides for the two planes of motion normally seen at the wrist; 90 degrees of flexion and extension and 50 degrees of radial ulnar deviation are permitted by the design. Candidates for total wrist arthroplasty are patients who exhibit far-advanced disease at the wrist and who might be considered as candidates for arthrodesis, but in whom the permanent loss of motion would represent a significant handicap. To date 17 arthroplasties have been performed in 14 patients. The longest follow-up is 14 months. All but 2 patients have gained a useful range of motion. All patients have noted dramatic relief of pain and deformity, permitting them to perform tasks which were preoperatively impossible.", "contents": "The development of a total wrist arthroplasty. For many individuals the preservation of wrist motion is essential for augmentation of fine motor control of the hand and fingers. When significant functional disability exists at the wrist, currently available surgical treatment includes soft tissue arthroplasty, carpectomy, or arthrodesis. A total wrist joint arthroplasty offers the patient the potential of a pain-free, stable, and mobile wrist. Based upon the principles of total joint replacement as applied to the hip and knee, the prosthesis is secured to the carpus and radius with methylmethacrylate cement, following removal of the navicular, lunate, and head of the capitate. The design of the prosthesis provides for the two planes of motion normally seen at the wrist; 90 degrees of flexion and extension and 50 degrees of radial ulnar deviation are permitted by the design. Candidates for total wrist arthroplasty are patients who exhibit far-advanced disease at the wrist and who might be considered as candidates for arthrodesis, but in whom the permanent loss of motion would represent a significant handicap. To date 17 arthroplasties have been performed in 14 patients. The longest follow-up is 14 months. All but 2 patients have gained a useful range of motion. All patients have noted dramatic relief of pain and deformity, permitting them to perform tasks which were preoperatively impossible."} {"id": "PMID:1277644", "title": "K\u00fcntscher intramedullary reaming and nail fixation for nonunion of the forearm.", "content": "Twenty cases of nonunion of forearm fractures were treated by the K\u00fcntscher method of intramedullary reaming and nailing. Fifteen fractures healed per primam; 2 required renailing; 2 did not heal but the patients benefited from the stabilizing effect of the nail; 1 was lost to follow-up. Even infected cases could be treated successfully by this method, but extensive experience with all the details of the surgical technique may constitute the difference between catastrophic failure and success. Excision of sinus tracts and sequestrectomy were done as a preliminary procedure.", "contents": "K\u00fcntscher intramedullary reaming and nail fixation for nonunion of the forearm. Twenty cases of nonunion of forearm fractures were treated by the K\u00fcntscher method of intramedullary reaming and nailing. Fifteen fractures healed per primam; 2 required renailing; 2 did not heal but the patients benefited from the stabilizing effect of the nail; 1 was lost to follow-up. Even infected cases could be treated successfully by this method, but extensive experience with all the details of the surgical technique may constitute the difference between catastrophic failure and success. Excision of sinus tracts and sequestrectomy were done as a preliminary procedure."} {"id": "PMID:1277645", "title": "K\u00fcntscher intramedullary reaming and nail fixation for nonunion of the humerus.", "content": "Thirteen cases of nonunion of the humerus were treated by intramedullary reaming and nail fixation. Rigid stabilization which was usual after operating upon other long bones was not always secured in these cases, and supplementary plaster immobilization was necessary. Seven fractures healed and 3 fractures required re-nailing before healing. Three fractures did not heal in spite of reoperation, but in 2 of these cases the nail provided stability and controlled pain and motion at fracture site. Nonunion of the humerus is a difficult problem, irrespective of the method of treatment.", "contents": "K\u00fcntscher intramedullary reaming and nail fixation for nonunion of the humerus. Thirteen cases of nonunion of the humerus were treated by intramedullary reaming and nail fixation. Rigid stabilization which was usual after operating upon other long bones was not always secured in these cases, and supplementary plaster immobilization was necessary. Seven fractures healed and 3 fractures required re-nailing before healing. Three fractures did not heal in spite of reoperation, but in 2 of these cases the nail provided stability and controlled pain and motion at fracture site. Nonunion of the humerus is a difficult problem, irrespective of the method of treatment."} {"id": "PMID:1277646", "title": "Dyschondrosteosis and Madelung's deformity. Report of three kindreds and review of the literature.", "content": "Dyschondrosteosis is a syndrome of Madelung's deformity, mesomelia and mild short stature that is transmitted by autosomal dominant inheritance. Most examples of Madelung's deformity are due to Dyschondrosteosis. Three affected kindreds are described, two having radiographically proven male to male transmission. A possible association with mental retardation has been postulated on the basis of its presence in four of eleven affected individuals in three kindreds. Dyschondrosteosis exhibits little functional impairment or cosmetic deformity suggesting that therapy is usually unnecessary.", "contents": "Dyschondrosteosis and Madelung's deformity. Report of three kindreds and review of the literature. Dyschondrosteosis is a syndrome of Madelung's deformity, mesomelia and mild short stature that is transmitted by autosomal dominant inheritance. Most examples of Madelung's deformity are due to Dyschondrosteosis. Three affected kindreds are described, two having radiographically proven male to male transmission. A possible association with mental retardation has been postulated on the basis of its presence in four of eleven affected individuals in three kindreds. Dyschondrosteosis exhibits little functional impairment or cosmetic deformity suggesting that therapy is usually unnecessary."} {"id": "PMID:1277647", "title": "Fat embolism syndrome: A comparison of hematologic coagulation and lipid changes in two animal models.", "content": "In considering intravenous injection of lipid as a model of fat embolism, contamination is frequent and purity must be demonstrated. Musculoskeletal trauma causes mild arterial hypoxia whereas intravenous pure triolein 0.1 mg/kg does not. Trauma produced a leukocytosis and elevated sedimentation rate not found in the lipid injected dogs. Evidence for consumptive coagulopathy was found in the trauma group but only a mild thrombocytopenia resulted from intravenous triolein. The traumatized dogs demonstrated an increase in the triglyceride level, an increase in the cholesterol phopholipid ratio and an increase in the cholesterol containing beta and prebeta lipoprotein fractions, all of which could lead to formation of pulmonary fat emboli containing cholesterol.", "contents": "Fat embolism syndrome: A comparison of hematologic coagulation and lipid changes in two animal models. In considering intravenous injection of lipid as a model of fat embolism, contamination is frequent and purity must be demonstrated. Musculoskeletal trauma causes mild arterial hypoxia whereas intravenous pure triolein 0.1 mg/kg does not. Trauma produced a leukocytosis and elevated sedimentation rate not found in the lipid injected dogs. Evidence for consumptive coagulopathy was found in the trauma group but only a mild thrombocytopenia resulted from intravenous triolein. The traumatized dogs demonstrated an increase in the triglyceride level, an increase in the cholesterol phopholipid ratio and an increase in the cholesterol containing beta and prebeta lipoprotein fractions, all of which could lead to formation of pulmonary fat emboli containing cholesterol."} {"id": "PMID:1277648", "title": "The femoral stem/cement interface in total hip replacement.", "content": "A study of the cement prosthesis interface has been carried out on the femoral component of 5 total hip relacements which had been in place between 7 weeks and 5 years. In every case a thin layer of connective tissue at varying stages of organization was present between the prosthesis and the cement. This suggests that the prosthesis is not rigidly fixed to the cement and is capable of micromovement. The gap presumably comes about by a combination of factors which include thermal expansion of the femoral stem, shrinkage of the cement and organization of the film of blood or tissue fluid present on the stem at the time of implantation. This information must be used when construction mathematical models of joint replacements, but its clinical significance is not yet fully clear.", "contents": "The femoral stem/cement interface in total hip replacement. A study of the cement prosthesis interface has been carried out on the femoral component of 5 total hip relacements which had been in place between 7 weeks and 5 years. In every case a thin layer of connective tissue at varying stages of organization was present between the prosthesis and the cement. This suggests that the prosthesis is not rigidly fixed to the cement and is capable of micromovement. The gap presumably comes about by a combination of factors which include thermal expansion of the femoral stem, shrinkage of the cement and organization of the film of blood or tissue fluid present on the stem at the time of implantation. This information must be used when construction mathematical models of joint replacements, but its clinical significance is not yet fully clear."} {"id": "PMID:1277649", "title": "Camptomelic dwarfism. Report of a case and review of the salient features.", "content": "A typical case of camptomelic dwarfism exhibits the characteristic clinical features of: rhizomelic dwarfism, anterior bowing of the tibia with cutaneous dimpling, talipes equinovarus, peculiar facies with micrognathia and characteristically death in the first 6 weeks of life.", "contents": "Camptomelic dwarfism. Report of a case and review of the salient features. A typical case of camptomelic dwarfism exhibits the characteristic clinical features of: rhizomelic dwarfism, anterior bowing of the tibia with cutaneous dimpling, talipes equinovarus, peculiar facies with micrognathia and characteristically death in the first 6 weeks of life."} {"id": "PMID:1277650", "title": "Dysplasia epiphysealis hemimelica. A case report.", "content": "Experience with a 9-year-old girl with Dysplasia Epiphysealis Hemimelica in the right lower extremity demonstrates that avoidance of confusion leading to medical--legal problems and promotion of effective management would have been possible by early recognition of the condition.", "contents": "Dysplasia epiphysealis hemimelica. A case report. Experience with a 9-year-old girl with Dysplasia Epiphysealis Hemimelica in the right lower extremity demonstrates that avoidance of confusion leading to medical--legal problems and promotion of effective management would have been possible by early recognition of the condition."} {"id": "PMID:1277651", "title": "The effects of phosphate and vitamin D therapy on osteopenic, hypophosphatemic osteomalacia of childhood.", "content": "Two severely osteopenic adolescent males with clinical manifestations of adult onset hypophosphatemic osteomalacia were resistant respectively to physiological and pharmacological doses of vitamin D. Clinical improvement ensued following initiation of pharmacological doses of vitamin D and phosphate. Non-decalcified bone biopsies obtained before and during therapy exhibited correction of an isolated mineralization in the second. The response to treatment was reflected in striking changes in tetracycline-labelled calcification fronts in both patients.", "contents": "The effects of phosphate and vitamin D therapy on osteopenic, hypophosphatemic osteomalacia of childhood. Two severely osteopenic adolescent males with clinical manifestations of adult onset hypophosphatemic osteomalacia were resistant respectively to physiological and pharmacological doses of vitamin D. Clinical improvement ensued following initiation of pharmacological doses of vitamin D and phosphate. Non-decalcified bone biopsies obtained before and during therapy exhibited correction of an isolated mineralization in the second. The response to treatment was reflected in striking changes in tetracycline-labelled calcification fronts in both patients."} {"id": "PMID:1277652", "title": "The Guillain-Barre syndrome in children. Orthopedic management and patterns of recovery.", "content": "Eleven cases of Guillain-Barre Syndrome in children between 1955 and 1973 demonstrate clinical course and residual permanent motor deficits. The rate of recovery from muscle paralysis and the long-term permanent muscle loss, and the resultant paralytic deficits may require treatment: tendon transfers, opponensplasties, spinal fusions, and Lambrinudi operations. The late permanent motor paralysis and residual joint deformities secondary to GBS in children has a higher incidence and severity than in adults, and an intensive rehabilitation program in imperative. Frequent, extended follow-up, and muscle testing records are absolutely essential in children.", "contents": "The Guillain-Barre syndrome in children. Orthopedic management and patterns of recovery. Eleven cases of Guillain-Barre Syndrome in children between 1955 and 1973 demonstrate clinical course and residual permanent motor deficits. The rate of recovery from muscle paralysis and the long-term permanent muscle loss, and the resultant paralytic deficits may require treatment: tendon transfers, opponensplasties, spinal fusions, and Lambrinudi operations. The late permanent motor paralysis and residual joint deformities secondary to GBS in children has a higher incidence and severity than in adults, and an intensive rehabilitation program in imperative. Frequent, extended follow-up, and muscle testing records are absolutely essential in children."} {"id": "PMID:1277653", "title": "Operative and non-operative treatment of rachitic lower extremity deformities. A long term study with forty-six year average follow-up.", "content": "The long term sequelae of rachitic deformities includes degenerative arthritis. Surgery at an early age will be beneficial in preventing degenerative arthritis in children with severe deformities. Of the many metabolic processes involved with Vitamin D, there must be some that vary quantitatively so that a small alteration may produce rickets in one child, go completely unnoticed in another, and persist in still another as a subclinical disease. Furthermore, it is entirely probable that some children then diagnosed as having classical D-deficiency rickets, in fact, would now be found to have D-resistant states.", "contents": "Operative and non-operative treatment of rachitic lower extremity deformities. A long term study with forty-six year average follow-up. The long term sequelae of rachitic deformities includes degenerative arthritis. Surgery at an early age will be beneficial in preventing degenerative arthritis in children with severe deformities. Of the many metabolic processes involved with Vitamin D, there must be some that vary quantitatively so that a small alteration may produce rickets in one child, go completely unnoticed in another, and persist in still another as a subclinical disease. Furthermore, it is entirely probable that some children then diagnosed as having classical D-deficiency rickets, in fact, would now be found to have D-resistant states."} {"id": "PMID:1277654", "title": "Multifocal subacute pyogenic osteomyelitis in a child. A case report.", "content": "The clinical features of multifocal subacute pyogenic osteomyelitis are: insidious onset; the absence of toxic reaction; radiographic appearance of a bone neoplasm. In a 14-year-old boy, immobilization and appropriate antibiotics produced symptomatic improvement and radiographic evidence of healing reactive bone above both bone lesions.", "contents": "Multifocal subacute pyogenic osteomyelitis in a child. A case report. The clinical features of multifocal subacute pyogenic osteomyelitis are: insidious onset; the absence of toxic reaction; radiographic appearance of a bone neoplasm. In a 14-year-old boy, immobilization and appropriate antibiotics produced symptomatic improvement and radiographic evidence of healing reactive bone above both bone lesions."} {"id": "PMID:1277655", "title": "Skeletal growth and development of the achondroplastic dwarf.", "content": "Certain patterns in growth and development can be seen in the typical achondroplastic dwarf. Height is approximatley 5 standard deviations below average size for age through the age of 14. Sitting height is within normal limits at all ages. On the average the femur is 8 standard deviations and the tibia 7 standard deviations below normal size. Compared to normal, both femur and tibia exhibit approximately a 50 per cent inhibition in growth. A slight decrease in the deviance from the norm is observed for all parameters during growth until the time of the adolescent growth spurt when an increased deviance is seen. Related to normal children of the same sex and age, females are more severely affected than male achondroplastic dwarfs. The skeletal development of the hand is irregular, often having extra metacarpal epiphyses and a wide variance in skeletal maturation assessment between the carpals and the rest of the hand. The skeletal age is generally below chronological age until the adolescent growth spurt when a rapid maturation pattern occurs. Standard skeletal age assessment techniques cannot be applied to the achondroplastic individual.", "contents": "Skeletal growth and development of the achondroplastic dwarf. Certain patterns in growth and development can be seen in the typical achondroplastic dwarf. Height is approximatley 5 standard deviations below average size for age through the age of 14. Sitting height is within normal limits at all ages. On the average the femur is 8 standard deviations and the tibia 7 standard deviations below normal size. Compared to normal, both femur and tibia exhibit approximately a 50 per cent inhibition in growth. A slight decrease in the deviance from the norm is observed for all parameters during growth until the time of the adolescent growth spurt when an increased deviance is seen. Related to normal children of the same sex and age, females are more severely affected than male achondroplastic dwarfs. The skeletal development of the hand is irregular, often having extra metacarpal epiphyses and a wide variance in skeletal maturation assessment between the carpals and the rest of the hand. The skeletal age is generally below chronological age until the adolescent growth spurt when a rapid maturation pattern occurs. Standard skeletal age assessment techniques cannot be applied to the achondroplastic individual."} {"id": "PMID:1277656", "title": "Iliac apophyses. Prognostic value in idiopathic schliosis.", "content": "Fusion of the iliac apophyses with the crests of the ilium is of greater prognostic value than completion of excursion of the iliac apophyses. Completion of fusion of the vertebral ring apophyses coincides with fusion of the iliac apophyses to the crests. For accurate evaluation of the progression of the scoliotic curve, patients should be followed a few years after fusion of the iliac apophyses although progression after this stage is rare.", "contents": "Iliac apophyses. Prognostic value in idiopathic schliosis. Fusion of the iliac apophyses with the crests of the ilium is of greater prognostic value than completion of excursion of the iliac apophyses. Completion of fusion of the vertebral ring apophyses coincides with fusion of the iliac apophyses to the crests. For accurate evaluation of the progression of the scoliotic curve, patients should be followed a few years after fusion of the iliac apophyses although progression after this stage is rare."} {"id": "PMID:1277657", "title": "Scoliosis treated by cast correction and spine fusion.", "content": "The foregoing long term follow-up examinations of 8 cases demonstrate that the increase of the scoliotic deformity can be prevented by spinal fusion. Correction can be maintained by fusion. One of the best methods of correction is a combination of traction and lateral bend. Spinal pain can be eliminated by fusion. Corrective holding casts can prevent increasing deformity during during the period of vertebral growth and may maintain some correction of the deformity.", "contents": "Scoliosis treated by cast correction and spine fusion. The foregoing long term follow-up examinations of 8 cases demonstrate that the increase of the scoliotic deformity can be prevented by spinal fusion. Correction can be maintained by fusion. One of the best methods of correction is a combination of traction and lateral bend. Spinal pain can be eliminated by fusion. Corrective holding casts can prevent increasing deformity during during the period of vertebral growth and may maintain some correction of the deformity."} {"id": "PMID:1277658", "title": "A biplane radiographic method of determining vertebral rotation in postmortem specimens.", "content": "Vertebral axial rotation can be measured by accurate identification of three bony landmarks: the tips of the superior articular facets; the inferior bases of the pedicles; the tips of the inferior articular facets. Geometric solution for the movement of these three points in space does not require an initial unrotated view, and can be proved with accuracy of up to 4 degrees in the thoracic spine and 3 degrees in the lumbar spine under experimental conditions. The method is applicable to the problem of measurement of structural scoliotic deformities on routine clinical roentgenograms.", "contents": "A biplane radiographic method of determining vertebral rotation in postmortem specimens. Vertebral axial rotation can be measured by accurate identification of three bony landmarks: the tips of the superior articular facets; the inferior bases of the pedicles; the tips of the inferior articular facets. Geometric solution for the movement of these three points in space does not require an initial unrotated view, and can be proved with accuracy of up to 4 degrees in the thoracic spine and 3 degrees in the lumbar spine under experimental conditions. The method is applicable to the problem of measurement of structural scoliotic deformities on routine clinical roentgenograms."} {"id": "PMID:1277659", "title": "Adolescent scoliosis patients. Personality patterns and effects of corrective surgery.", "content": "Personality patterns of 84 adolescent scoliosis patients were assessed and an evaluation made of certain psychological effects of corrective surgery. Results indicate the following: Scoliosis has fewer psychologically debilitating effects on younger adolescents (those under 16) than it does on older adolescents; scoliotic boys show comparatively better general personality integration than girls; scoliotic girls are less disturbed in psychosexual development than are boys. Postoperatively, boys can be expected to show less overt incapacitation than girls; psychologically, boys will require a longer period of recuperation than will girls; boys can be expected to present fewer immediate management problems than girls; the internalization of a sense of \"difference\" from the normal in adolescent scoliotics increases in direct relation to age. Consequently, the eariler surgical correction can be undertaken the better. Important differences exist between the psychological \"set\" of male and female adolescent patients. For boys, self-acceptance is at the core. Postoperative surgical care should thus focus on reinforcing characteristics of personal adequacy, namely, the ability to compete, and fulfill reasonable goals. For girls, acceptance by others is paramount. Postoperative care is best directed toward strengthening feelings of attractiveness (of any personal characteristic), worth, and, above all, future interpersonal possibilities.", "contents": "Adolescent scoliosis patients. Personality patterns and effects of corrective surgery. Personality patterns of 84 adolescent scoliosis patients were assessed and an evaluation made of certain psychological effects of corrective surgery. Results indicate the following: Scoliosis has fewer psychologically debilitating effects on younger adolescents (those under 16) than it does on older adolescents; scoliotic boys show comparatively better general personality integration than girls; scoliotic girls are less disturbed in psychosexual development than are boys. Postoperatively, boys can be expected to show less overt incapacitation than girls; psychologically, boys will require a longer period of recuperation than will girls; boys can be expected to present fewer immediate management problems than girls; the internalization of a sense of \"difference\" from the normal in adolescent scoliotics increases in direct relation to age. Consequently, the eariler surgical correction can be undertaken the better. Important differences exist between the psychological \"set\" of male and female adolescent patients. For boys, self-acceptance is at the core. Postoperative surgical care should thus focus on reinforcing characteristics of personal adequacy, namely, the ability to compete, and fulfill reasonable goals. For girls, acceptance by others is paramount. Postoperative care is best directed toward strengthening feelings of attractiveness (of any personal characteristic), worth, and, above all, future interpersonal possibilities."} {"id": "PMID:1277660", "title": "Surgical treatment for spondylolisthesis in the adult.", "content": "There are 3 common types of spondylolisthesis: dysplastic; isthmic; degenerative. This classification, presented anew in an article published in this volume, evolved from a discussion by the members of the International Society for the Study of the Lumbar spine. The surgical treatment is designed to correct a combination of symptomatic and mechanical abnormalities characteristic of each type.", "contents": "Surgical treatment for spondylolisthesis in the adult. There are 3 common types of spondylolisthesis: dysplastic; isthmic; degenerative. This classification, presented anew in an article published in this volume, evolved from a discussion by the members of the International Society for the Study of the Lumbar spine. The surgical treatment is designed to correct a combination of symptomatic and mechanical abnormalities characteristic of each type."} {"id": "PMID:1277661", "title": "Late results of removal of the loose posterior element (Gill's operation) in the treatment of lytic lumbar spondylolisthesis.", "content": "This study presents the late results of the Gill operation for the treatment of lytic lumbar spondylolisthesis in 75 patients. The observation time ranged for 5 to 20 years, averaging 12 years. Primary results were excellent, good or fair in 83 per cent at the end of 1 year. However, the figures dropped to 75 per cent when the cases were evaluated 5 or more years after operation. The worsening of the results during the observation time seems to depend on the degeneration of the intervertebral disk. Progression of olisthesis was observed in 27 per cent of the patients, usually in connection with progression of disk degeneration. This progression did not affect the clinical result of treatment. Nine patients had a lumbar disk herniation, 8 from a segment above the level of defect and 1 at that level. On 9 patients a fusion was later performed as a secondary operation. In these the late result was still unsatisfactory in all but 2. The operation is contraindicated in adolescents except in exceptional cases with signs of compression of the cauda equina. It is not recommended for patients below the age of 30 years. The main indication for the Gill operation is painful spondylolisthesis with nerve root symptoms in patients over 40 years of age.", "contents": "Late results of removal of the loose posterior element (Gill's operation) in the treatment of lytic lumbar spondylolisthesis. This study presents the late results of the Gill operation for the treatment of lytic lumbar spondylolisthesis in 75 patients. The observation time ranged for 5 to 20 years, averaging 12 years. Primary results were excellent, good or fair in 83 per cent at the end of 1 year. However, the figures dropped to 75 per cent when the cases were evaluated 5 or more years after operation. The worsening of the results during the observation time seems to depend on the degeneration of the intervertebral disk. Progression of olisthesis was observed in 27 per cent of the patients, usually in connection with progression of disk degeneration. This progression did not affect the clinical result of treatment. Nine patients had a lumbar disk herniation, 8 from a segment above the level of defect and 1 at that level. On 9 patients a fusion was later performed as a secondary operation. In these the late result was still unsatisfactory in all but 2. The operation is contraindicated in adolescents except in exceptional cases with signs of compression of the cauda equina. It is not recommended for patients below the age of 30 years. The main indication for the Gill operation is painful spondylolisthesis with nerve root symptoms in patients over 40 years of age."} {"id": "PMID:1277662", "title": "Guidelines for the management of lumbosacral spondylolisthesis associated with scoliosis.", "content": "Lumbosacral spondylolisthesis, when it is associated with scoliosis, presents special problems which require special consideration in management. Lumbosacral spondylosisthesis associated with a major thoracic curve, presents two separate problems. Treatment of the lumbosacral spondylolisthesis depends upon the severity of the lesion and symptoms. The thoracic curve is treated as required, depending upon the severity of the scoliosis and the stage of spinal maturation. Lumbosacral spondylolisthesis associated with a thoracolumbar or lumbar curve requires treatment of the curves above, along with the spondylolisthesis. Do not fuse the lumbosacral joint in an uncorrected position.", "contents": "Guidelines for the management of lumbosacral spondylolisthesis associated with scoliosis. Lumbosacral spondylolisthesis, when it is associated with scoliosis, presents special problems which require special consideration in management. Lumbosacral spondylosisthesis associated with a major thoracic curve, presents two separate problems. Treatment of the lumbosacral spondylolisthesis depends upon the severity of the lesion and symptoms. The thoracic curve is treated as required, depending upon the severity of the scoliosis and the stage of spinal maturation. Lumbosacral spondylolisthesis associated with a thoracolumbar or lumbar curve requires treatment of the curves above, along with the spondylolisthesis. Do not fuse the lumbosacral joint in an uncorrected position."} {"id": "PMID:1277663", "title": "Spinal instrumentation in the treatment of severe progressive spondylolisthesis.", "content": "By using A-frame instrumentation and direct distraction force, an exceptional correction can be obtained in patients with severe spondylolisthesis. Adolescent progressive spondylolisthesis should be considered as an entity separate from the lumbosacral anomalies such as spondylolysis and grades 0 and 1 spondylolisthesis without progression. An aplastic relationship appears to exist between the sacrum and the posterior superior wing of the ilium in the adolescent with progressive spondylolisthesis. Complications have been minimal but long-term observations of patients are necessary to evaluate the contribution of instrumentation in the treatment for severe progressive spondylolisthesis.", "contents": "Spinal instrumentation in the treatment of severe progressive spondylolisthesis. By using A-frame instrumentation and direct distraction force, an exceptional correction can be obtained in patients with severe spondylolisthesis. Adolescent progressive spondylolisthesis should be considered as an entity separate from the lumbosacral anomalies such as spondylolysis and grades 0 and 1 spondylolisthesis without progression. An aplastic relationship appears to exist between the sacrum and the posterior superior wing of the ilium in the adolescent with progressive spondylolisthesis. Complications have been minimal but long-term observations of patients are necessary to evaluate the contribution of instrumentation in the treatment for severe progressive spondylolisthesis."} {"id": "PMID:1277664", "title": "Spondylolisthesis following surgical fusion for scoliosis: a case report.", "content": "This is a case report of a 25-year-old woman who developed spondylolisthesis following surgical spine fusion for treatment of congenital scoliosis. Increased biomechanical stresses and the possibility of an undetected pars interarticularis defect existing prior to fusion are considered as etiological factors in this progressive lesion.", "contents": "Spondylolisthesis following surgical fusion for scoliosis: a case report. This is a case report of a 25-year-old woman who developed spondylolisthesis following surgical spine fusion for treatment of congenital scoliosis. Increased biomechanical stresses and the possibility of an undetected pars interarticularis defect existing prior to fusion are considered as etiological factors in this progressive lesion."} {"id": "PMID:1277665", "title": "Long term follow-up of patients with idiopathic scoliosis treated surgically: a preliminary subjective study.", "content": "An 8 to 14-year follow-up study of 51 surgically-treated patients with idiopathic scoliosis was performed to determine the impact upon their total life styles, and the differences in comparable but non-surgically-treated patients. Forty-nine per cent were already married and raising families and 70 per cent had been educated beyond high school. Ninety-four per cent were actively employed although 20 per cent had met with some type of job discrimination. None of the unemployed was rejected because of back symptoms. Eighty-six per cent of the patients experienced either no back symptoms or just an annoying but nonrestrictive type of low back pain. Most of the patients experiencing significant back pain were found to have tight hamstrings. Only 4 per cent of the patients required hospitalization for back symptoms and another 4 per cent relied on the use of a lumbar corset to relieve their back strain. Seventy-eight per cent of the patients were quite active in sports and other strenuous activities. Fifty-one per cent of the patients were motivated for cosmetic reasons to undergo the corrective surgery. Postoperatively, 33 per cent were still self-conscious of their scar and 43 per cent were bothered with a residual deformity. Only 10 per cent, however, expressed an overall dissatisfaction with the total result.", "contents": "Long term follow-up of patients with idiopathic scoliosis treated surgically: a preliminary subjective study. An 8 to 14-year follow-up study of 51 surgically-treated patients with idiopathic scoliosis was performed to determine the impact upon their total life styles, and the differences in comparable but non-surgically-treated patients. Forty-nine per cent were already married and raising families and 70 per cent had been educated beyond high school. Ninety-four per cent were actively employed although 20 per cent had met with some type of job discrimination. None of the unemployed was rejected because of back symptoms. Eighty-six per cent of the patients experienced either no back symptoms or just an annoying but nonrestrictive type of low back pain. Most of the patients experiencing significant back pain were found to have tight hamstrings. Only 4 per cent of the patients required hospitalization for back symptoms and another 4 per cent relied on the use of a lumbar corset to relieve their back strain. Seventy-eight per cent of the patients were quite active in sports and other strenuous activities. Fifty-one per cent of the patients were motivated for cosmetic reasons to undergo the corrective surgery. Postoperatively, 33 per cent were still self-conscious of their scar and 43 per cent were bothered with a residual deformity. Only 10 per cent, however, expressed an overall dissatisfaction with the total result."} {"id": "PMID:1277667", "title": "Compression fixation of subtrochanteric fractures.", "content": "Compression fixation with a blade plate was used in the treatment of 11 fresh and 9 nonunited subtrochanteric fractures. Fifteen fractures united as fixed. Three settled into varus with eventual union in 2 and a fibrous nonunion with metal failure in one. One fracture became infected and the patient died of metastatic fibrosarcoma and one was lost to accurate long-term follow-up. The average Harris Hip Rating for 18 patients was 84, an average of 24 postoperatively. In each instance, technical errors accounted for suboptimal results. Compression fixation is designed for the subtrochanteric region for either fresh or nonunited fractures.", "contents": "Compression fixation of subtrochanteric fractures. Compression fixation with a blade plate was used in the treatment of 11 fresh and 9 nonunited subtrochanteric fractures. Fifteen fractures united as fixed. Three settled into varus with eventual union in 2 and a fibrous nonunion with metal failure in one. One fracture became infected and the patient died of metastatic fibrosarcoma and one was lost to accurate long-term follow-up. The average Harris Hip Rating for 18 patients was 84, an average of 24 postoperatively. In each instance, technical errors accounted for suboptimal results. Compression fixation is designed for the subtrochanteric region for either fresh or nonunited fractures."} {"id": "PMID:1277668", "title": "Heterotopic bone formation after total hip arthroplasty.", "content": "Heterotopic bone formation is a common complication of total hip arthroplasty. A certain degree of heterotopic bone formation occurs in about one-half of the patients in degrees ranging from very mild to moderate involvement. The patients do not necessarily have any clinical disability; only 2 per cent of the patients developed severe heterotopic bone radiographically, and unsatisfactory functional results. There is no sex predilection for heterotopic bone formation except that the condition appears more severe in females. All ages are equally affected. The underlying disease process in the hip does not influence the occurrence of heterotopic bone. The incidence was significantly greater in patients who developed postoperative hematomas, prolonged wound drainage, or superficial infection. When surgical exposure is difficult and retraction of soft tissue aand soft tissue damage takes place, the incidence is much greater. Patients who have undergone previous surgical procedures about the hip present a greater risk in regards to development of disabling heterotopic bone formation. The etiology of heterotopic bone formation is not known. The following steps should be taken to avoid or greatly minimize the development of heterotopic bone: meticulous exposure with most careful retraction, copious irrigation with antibiotic solution, debridement of devitalized tissue prior to closure, instillation of drainage tubes, intraoperative and postoperative antibiotics, and carefully controlled postoperative anticoagulation.", "contents": "Heterotopic bone formation after total hip arthroplasty. Heterotopic bone formation is a common complication of total hip arthroplasty. A certain degree of heterotopic bone formation occurs in about one-half of the patients in degrees ranging from very mild to moderate involvement. The patients do not necessarily have any clinical disability; only 2 per cent of the patients developed severe heterotopic bone radiographically, and unsatisfactory functional results. There is no sex predilection for heterotopic bone formation except that the condition appears more severe in females. All ages are equally affected. The underlying disease process in the hip does not influence the occurrence of heterotopic bone. The incidence was significantly greater in patients who developed postoperative hematomas, prolonged wound drainage, or superficial infection. When surgical exposure is difficult and retraction of soft tissue aand soft tissue damage takes place, the incidence is much greater. Patients who have undergone previous surgical procedures about the hip present a greater risk in regards to development of disabling heterotopic bone formation. The etiology of heterotopic bone formation is not known. The following steps should be taken to avoid or greatly minimize the development of heterotopic bone: meticulous exposure with most careful retraction, copious irrigation with antibiotic solution, debridement of devitalized tissue prior to closure, instillation of drainage tubes, intraoperative and postoperative antibiotics, and carefully controlled postoperative anticoagulation."} {"id": "PMID:1277669", "title": "Classification of spondylolisis and spondylolisthesis.", "content": "A working classification of spondylolysis and spondylolisthesis which encompasses the salient features of the disorder, has been presented. It is based on both etiological and anatomical factors.", "contents": "Classification of spondylolisis and spondylolisthesis. A working classification of spondylolysis and spondylolisthesis which encompasses the salient features of the disorder, has been presented. It is based on both etiological and anatomical factors."} {"id": "PMID:1277670", "title": "Combined trochanteric and ipsilateral shaft fractures of the femur treated with the Zickel device: a case report.", "content": "An unusual double fracture of the femur in the trochanteric and shaft areas of a 39-year-old clerical worker has been successfully treated by open reduction and internal fixation with the Zickel device. Only one other instance of the application of this method to a double fracture seems to have been reported previously. Recovery was uneventful, prompt, and the patient showed good evidence of healing at the 10-month followup examination. The described case represents the seventh report of this unusual lesion in the literature.", "contents": "Combined trochanteric and ipsilateral shaft fractures of the femur treated with the Zickel device: a case report. An unusual double fracture of the femur in the trochanteric and shaft areas of a 39-year-old clerical worker has been successfully treated by open reduction and internal fixation with the Zickel device. Only one other instance of the application of this method to a double fracture seems to have been reported previously. Recovery was uneventful, prompt, and the patient showed good evidence of healing at the 10-month followup examination. The described case represents the seventh report of this unusual lesion in the literature."} {"id": "PMID:1277671", "title": "Pycnodysostosis presenting with bilateral subtrachanteric fractures: case report.", "content": "A 50-year-old woman had bilateral subtrochanteric fractures over a period of 9 months; both fractures were found to be in osteosclerotic femora. The patient was multiparous with 5 normal children. Since subtrochanteric fractures represent only 5 per cent of all femoral neck fractures the occurrence of bilateral subtrochanteric fractures in a relatively young woman suggested an unsuspected underlying disease. Clinical and laboratory investigations showed no evidence of systemic, metabolic, infective or malignant disease. The patient's short stature, peculiar facies in association with osteosclerosis in medullated long bones and typical radiographic findings: hypoplastic claviculae, absent ungual tufts of distal phalanges, hypoplastic paranasal sinuses, and obtuse mandibular angles suggested the proposed diagnosis of pycnodysostosis, a rare autosomal recessive osteosclerotic condition, that has been described in less than 50 cases, including only one Jew. Despite 2 technically difficult surgical hip operations, a 3-year follow-up showed good remedullarization of both fractured femora and no limitation in the patient's daily activities.", "contents": "Pycnodysostosis presenting with bilateral subtrachanteric fractures: case report. A 50-year-old woman had bilateral subtrochanteric fractures over a period of 9 months; both fractures were found to be in osteosclerotic femora. The patient was multiparous with 5 normal children. Since subtrochanteric fractures represent only 5 per cent of all femoral neck fractures the occurrence of bilateral subtrochanteric fractures in a relatively young woman suggested an unsuspected underlying disease. Clinical and laboratory investigations showed no evidence of systemic, metabolic, infective or malignant disease. The patient's short stature, peculiar facies in association with osteosclerosis in medullated long bones and typical radiographic findings: hypoplastic claviculae, absent ungual tufts of distal phalanges, hypoplastic paranasal sinuses, and obtuse mandibular angles suggested the proposed diagnosis of pycnodysostosis, a rare autosomal recessive osteosclerotic condition, that has been described in less than 50 cases, including only one Jew. Despite 2 technically difficult surgical hip operations, a 3-year follow-up showed good remedullarization of both fractured femora and no limitation in the patient's daily activities."} {"id": "PMID:1277672", "title": "The use of banked autologous blood in total hip replacement surgery.", "content": "Fifty patients anticipating total hip replacement, with an average age of 63, donated 125 units of blood in an organized autologous transfusion program. All but 3 patients demonstrated the ability to respond to oral iron and maintain adequate hemoglobin levels for subsequent phlebotomies. No complications were encountered and the program was well received by the participating patients. The advantages of autologous transfusion are numerous, including the avoidance of the risk of serum hepatitis, blood reactions, blood incompatibilities. Autologous transfusion constitutes a source of blood availability in the elective procedure of total hip replacement. This procedure is safe, practical and well tolerated.", "contents": "The use of banked autologous blood in total hip replacement surgery. Fifty patients anticipating total hip replacement, with an average age of 63, donated 125 units of blood in an organized autologous transfusion program. All but 3 patients demonstrated the ability to respond to oral iron and maintain adequate hemoglobin levels for subsequent phlebotomies. No complications were encountered and the program was well received by the participating patients. The advantages of autologous transfusion are numerous, including the avoidance of the risk of serum hepatitis, blood reactions, blood incompatibilities. Autologous transfusion constitutes a source of blood availability in the elective procedure of total hip replacement. This procedure is safe, practical and well tolerated."} {"id": "PMID:1277673", "title": "Indicators of recovery from fractures of the hip.", "content": "Patients with similar injuries who were at a similar level of function before the injury differ in the extent of recovery. In an attempt to identify important factors that affect recovery, we collected extensive physical, psychological and sociological data on a group of 108 elderly people with fractures of the hip in order to study the influence of the many variables on their recovery. We found that of all the items studied, those that best indicated the degree of recovery were: (1) the physical therapist's rating of functional ability; (2) how often the patient got outside the home prior to injury; (3) the patient's mental clarity.", "contents": "Indicators of recovery from fractures of the hip. Patients with similar injuries who were at a similar level of function before the injury differ in the extent of recovery. In an attempt to identify important factors that affect recovery, we collected extensive physical, psychological and sociological data on a group of 108 elderly people with fractures of the hip in order to study the influence of the many variables on their recovery. We found that of all the items studied, those that best indicated the degree of recovery were: (1) the physical therapist's rating of functional ability; (2) how often the patient got outside the home prior to injury; (3) the patient's mental clarity."} {"id": "PMID:1277674", "title": "Ligament length patterns, strength, and rotational axes of the knee joint.", "content": "Using intact fresh specimens, the cruciate ligament lengths for positions of flexion and internal-external rotation were computed using a non-invasive technique; using photographic methods, the centers of transverse rotation on the tibia and the direction of the flexion axis were also obtained. The anterior cruciate was found to be particularly effective in restraining internal tibial rotation; the ability of the posterior cruciate to restrain external rotation, however, depended strongly on the transverse axis location. Ligament length changes during flexion were found to be small in the absence of rotary torque and anteroposterior forces. The average internal rotation occurring during flexion was 37 degrees, half of which took place during the first 15 degrees of flexion. Ultimate rupture strengths of approximately 60 kh for the cruciates were measured, with stiffnesses of 16 kg/mm.", "contents": "Ligament length patterns, strength, and rotational axes of the knee joint. Using intact fresh specimens, the cruciate ligament lengths for positions of flexion and internal-external rotation were computed using a non-invasive technique; using photographic methods, the centers of transverse rotation on the tibia and the direction of the flexion axis were also obtained. The anterior cruciate was found to be particularly effective in restraining internal tibial rotation; the ability of the posterior cruciate to restrain external rotation, however, depended strongly on the transverse axis location. Ligament length changes during flexion were found to be small in the absence of rotary torque and anteroposterior forces. The average internal rotation occurring during flexion was 37 degrees, half of which took place during the first 15 degrees of flexion. Ultimate rupture strengths of approximately 60 kh for the cruciates were measured, with stiffnesses of 16 kg/mm."} {"id": "PMID:1277675", "title": "Solitary intraosseous neurilemmoma of the tibia: review of intraosseous neurilemmoma and neurofibroma.", "content": "This is a case report of a 59-year-old woman with a neurilemmoma involving the tibia, a site not previously reported for this tumor. Neurilemmoma, a benign neoplasm which rarely involves bone, arises from the Schwann cells in the nerve sheath. It is a distinct pathological entity separate from solitary neurofibroma, and arises from the connective tissue coats of nerves, but which also involves bone. The incidence of the 2 types of nerve sheath tumors is obscured by the tendency of some authors to use the terms interchangeably. Forty-eight cases of true intraosseous neurilemmoma have been reported in the literature. Of 18 cases of solitary intraosseous neurofibroma primary in bone, all were in the jaw and 6 were malignant. The diagnosis of intraosseous neurilemmoma may be missed because of its rarity and roentgenologic appearance of cystic bone disease which is not distinctive except that it resembles other commonly encountered bone lesions. A positive diagnosis is based only on the microscopic pathology. Complete local resection generally produces an excellent result without recurrence.", "contents": "Solitary intraosseous neurilemmoma of the tibia: review of intraosseous neurilemmoma and neurofibroma. This is a case report of a 59-year-old woman with a neurilemmoma involving the tibia, a site not previously reported for this tumor. Neurilemmoma, a benign neoplasm which rarely involves bone, arises from the Schwann cells in the nerve sheath. It is a distinct pathological entity separate from solitary neurofibroma, and arises from the connective tissue coats of nerves, but which also involves bone. The incidence of the 2 types of nerve sheath tumors is obscured by the tendency of some authors to use the terms interchangeably. Forty-eight cases of true intraosseous neurilemmoma have been reported in the literature. Of 18 cases of solitary intraosseous neurofibroma primary in bone, all were in the jaw and 6 were malignant. The diagnosis of intraosseous neurilemmoma may be missed because of its rarity and roentgenologic appearance of cystic bone disease which is not distinctive except that it resembles other commonly encountered bone lesions. A positive diagnosis is based only on the microscopic pathology. Complete local resection generally produces an excellent result without recurrence."} {"id": "PMID:1277676", "title": "Total elbow replacement.", "content": "This is a report of a total elbow low friction arthroplasty consisting of a vitallium humeral component and a high density polyethylene ulnar component equipped with a special snap-lock fit joint. The immediate results in 16 patients are most encouraging.", "contents": "Total elbow replacement. This is a report of a total elbow low friction arthroplasty consisting of a vitallium humeral component and a high density polyethylene ulnar component equipped with a special snap-lock fit joint. The immediate results in 16 patients are most encouraging."} {"id": "PMID:1277677", "title": "Flexion and extension contracture of the elbow: surgical management.", "content": "In those cases in which a contracted capsule at the elbow limits flexion or extension, surgical treatment is warranted. A wide exposure is necessary to identify vital structures and perform an adequate anterior capsulectomy. A direct approach through the triceps is recommended for posterior capsulectomy. In 6 cases, the results were good when the contracture of the capsule was not associated with skin contracture or bony deformity.", "contents": "Flexion and extension contracture of the elbow: surgical management. In those cases in which a contracted capsule at the elbow limits flexion or extension, surgical treatment is warranted. A wide exposure is necessary to identify vital structures and perform an adequate anterior capsulectomy. A direct approach through the triceps is recommended for posterior capsulectomy. In 6 cases, the results were good when the contracture of the capsule was not associated with skin contracture or bony deformity."} {"id": "PMID:1277678", "title": "Corrective surgery for the deforming hand arthropathy of systemic lupus erythematosus.", "content": "A 33-year-old woman with deforming but non-erosive hand arthropathy typical of SLE had recurring digital subluxations and swan neck deformities after soft tissue procedures. Stronger grip and pinch as well as improved appearance were achieved with thumb MCP fusion and finger MCP silastic implants.", "contents": "Corrective surgery for the deforming hand arthropathy of systemic lupus erythematosus. A 33-year-old woman with deforming but non-erosive hand arthropathy typical of SLE had recurring digital subluxations and swan neck deformities after soft tissue procedures. Stronger grip and pinch as well as improved appearance were achieved with thumb MCP fusion and finger MCP silastic implants."} {"id": "PMID:1277679", "title": "Acute hematogenous osteomyelitis complicating closed fractures.", "content": "Five cases of acute hematogenous osteomyelitis occurring at the site of closed fractures are reported. This is a serious and potentially lethal complication resulting in directly in the death of 3 of the 5 patients. This is an unusual occurrence seen infrequently, and subsequent delay in diagnosis is frequent. An awareness of this complication (which usually occurs in the face of decreased resistance to infection) coupled with careful inspection of the fracture site, evaluation of the patient as a whole, and a high index of suspicion will allow earlier diagnosis and possibly more successful early treatment. Because of the pathophysiology of this lesion and the usual delay in diagnosis, initial treatment should include wide surgical drainage of the abscess with proper debridement and bony resection. This may involve procedures which at first glance may appear to be mutilating. In these patients with decreased resistance to infection, the initial appropriate choice of antibiotics is essential.", "contents": "Acute hematogenous osteomyelitis complicating closed fractures. Five cases of acute hematogenous osteomyelitis occurring at the site of closed fractures are reported. This is a serious and potentially lethal complication resulting in directly in the death of 3 of the 5 patients. This is an unusual occurrence seen infrequently, and subsequent delay in diagnosis is frequent. An awareness of this complication (which usually occurs in the face of decreased resistance to infection) coupled with careful inspection of the fracture site, evaluation of the patient as a whole, and a high index of suspicion will allow earlier diagnosis and possibly more successful early treatment. Because of the pathophysiology of this lesion and the usual delay in diagnosis, initial treatment should include wide surgical drainage of the abscess with proper debridement and bony resection. This may involve procedures which at first glance may appear to be mutilating. In these patients with decreased resistance to infection, the initial appropriate choice of antibiotics is essential."} {"id": "PMID:1277680", "title": "Etiology of spondylolisthesis.", "content": "The etiology of spondylolisthesis is multiple according to the type of the vertebral slipping. In fact all the following basic pathological processes may be involved: congenital malformation of the upper sacrum in the dysplastic spondylolisthesis; growth dysplasia of the vertebral arch in the \"isthmic spondylolisthesis\" where an hereditary background and mechanical stresses play a determining role; degenerative conditions of the intervertebral joints in \"degenerative spondylolisthesis\" of Newman or the \"pseudospondylolisthesis\" of Junghanns; infections and benign or malignant tumors destroying the articular bolt maintaining the vertebral line; traumatic lesions such as multiple fractures of the bony hook or much more rarely an isolated bilateral fracture of the pars interarticularis.", "contents": "Etiology of spondylolisthesis. The etiology of spondylolisthesis is multiple according to the type of the vertebral slipping. In fact all the following basic pathological processes may be involved: congenital malformation of the upper sacrum in the dysplastic spondylolisthesis; growth dysplasia of the vertebral arch in the \"isthmic spondylolisthesis\" where an hereditary background and mechanical stresses play a determining role; degenerative conditions of the intervertebral joints in \"degenerative spondylolisthesis\" of Newman or the \"pseudospondylolisthesis\" of Junghanns; infections and benign or malignant tumors destroying the articular bolt maintaining the vertebral line; traumatic lesions such as multiple fractures of the bony hook or much more rarely an isolated bilateral fracture of the pars interarticularis."} {"id": "PMID:1277681", "title": "Evaluation of microbial contamination of surgical gloves during actual use.", "content": "The contamination rate of gloves is about the same for all scrubbed personnel, be they single or double gloves (33%). More holes are noted in the gloves of personnel who use their hands more strenuously. A double pair of gloves does not reduce the amount of contamination but does reduce the number of holes. The contamination could not be associated with the hole in the glove in our study. The amount of contamination beneath the glove does not influence its exterior contamination. Contamination generally comes from somewhere else in the operative field environment.", "contents": "Evaluation of microbial contamination of surgical gloves during actual use. The contamination rate of gloves is about the same for all scrubbed personnel, be they single or double gloves (33%). More holes are noted in the gloves of personnel who use their hands more strenuously. A double pair of gloves does not reduce the amount of contamination but does reduce the number of holes. The contamination could not be associated with the hole in the glove in our study. The amount of contamination beneath the glove does not influence its exterior contamination. Contamination generally comes from somewhere else in the operative field environment."} {"id": "PMID:1277682", "title": "Metabolic balances of strontium in man.", "content": "Stable strontium balances were determined in man under strictly controlled dietary conditions in control studies and during both oral and intravenous administration of stable strontium. The diet contained about 1 mg strontium per day and most of this (88%) was excreted in stool while 17.5 per cent was excreted in urine, so that the balance was very slightly negative. During the oral intake of 1536 mg strontium per day, given as the lactate, the urinary and the fecal strontium excretions increased markedly and the balance became strongly positive. During the 6-day periods of intravenous infusions of stable strontium as the gluconate, 30-40 per cent of the infused amount was excreted in the urine and 5-10 per cent in stool. A high percentage of the strontium retained during both oral and intravenous administration was excreted in 30 days after the discontinuation of the strontium administration and there was no evidence of long term retention. The administration of stable strontium, given either orally or intravenously, was associated with an increase of the urinary calcium excretion.", "contents": "Metabolic balances of strontium in man. Stable strontium balances were determined in man under strictly controlled dietary conditions in control studies and during both oral and intravenous administration of stable strontium. The diet contained about 1 mg strontium per day and most of this (88%) was excreted in stool while 17.5 per cent was excreted in urine, so that the balance was very slightly negative. During the oral intake of 1536 mg strontium per day, given as the lactate, the urinary and the fecal strontium excretions increased markedly and the balance became strongly positive. During the 6-day periods of intravenous infusions of stable strontium as the gluconate, 30-40 per cent of the infused amount was excreted in the urine and 5-10 per cent in stool. A high percentage of the strontium retained during both oral and intravenous administration was excreted in 30 days after the discontinuation of the strontium administration and there was no evidence of long term retention. The administration of stable strontium, given either orally or intravenously, was associated with an increase of the urinary calcium excretion."} {"id": "PMID:1277683", "title": "The relation between densitometric and quantitative histological analysis of bone specimens from the iliac crest.", "content": "Roentgendensitometric measurements were correlated with quantitative histological analysis of cortical and cancellous bone from a standard anatomical site on the iliac crest. The point-count method was used to quantitate spongy bone in 8 mu thick sections. Measurements of the thickness of the cortices were made with a micrometric eyepiece. The reproducibility of the method for the roentgendensitometric analysis was found to be about 1 per cent of the mean for all variables. The correlation between roentgendensitometric and histological analysis was found to be low (r=0.44) and could be ascribed mainly to variation in the thickness of the cortices which again was only slightly correlated with the percentage of spongy bone (r=0.39). Both the determination of the amount of bone mineral and of bone by quantitative histometric analysis are required for diagnosis of skeletal system disorders.", "contents": "The relation between densitometric and quantitative histological analysis of bone specimens from the iliac crest. Roentgendensitometric measurements were correlated with quantitative histological analysis of cortical and cancellous bone from a standard anatomical site on the iliac crest. The point-count method was used to quantitate spongy bone in 8 mu thick sections. Measurements of the thickness of the cortices were made with a micrometric eyepiece. The reproducibility of the method for the roentgendensitometric analysis was found to be about 1 per cent of the mean for all variables. The correlation between roentgendensitometric and histological analysis was found to be low (r=0.44) and could be ascribed mainly to variation in the thickness of the cortices which again was only slightly correlated with the percentage of spongy bone (r=0.39). Both the determination of the amount of bone mineral and of bone by quantitative histometric analysis are required for diagnosis of skeletal system disorders."} {"id": "PMID:1277685", "title": "The mechanical etiology of spondylolysis and spondylolisthesis.", "content": "There are 3 mechanisms that may result in failure of the neural arch with or without displacement of the vertebral body of the pathological vertebral: flexion overload, unbalanced shear forces and forced rotation. It is understood that all types of overload may be applied simultaneously and in various combinations. Of all the forces acting on the lumbar spine torsional violence is the most disruptive of the neural arch. Besides causing olisthesis, it is also capable of producing lysis of the pars especially if the dorsal spine has the added restraint of high tensile stresses in the posterior ligamentous system. Under normal conditions, the L5-S1 intervertebral joint is subject to the highest forces and it therefore receives the first damage. However, in the presence of antiverse process, damaging stress occurs in the next higher joint. While the antitorsional large transverse process may protect the L5-S1 joint from torsion, it may not protect the L5 vertebra from excessive flexional strains that may fracture the pars. Though lysis may occur in both instances, paradoxically spondylolysis and spondylolisthesis are mutually exclusive conditions. It has long been thought that shear force imbalance was the causative agent in olisthesis. This mechanism remains unconvincing except possibly in instances where there is a pathological condition affecting the skeletal tissue.", "contents": "The mechanical etiology of spondylolysis and spondylolisthesis. There are 3 mechanisms that may result in failure of the neural arch with or without displacement of the vertebral body of the pathological vertebral: flexion overload, unbalanced shear forces and forced rotation. It is understood that all types of overload may be applied simultaneously and in various combinations. Of all the forces acting on the lumbar spine torsional violence is the most disruptive of the neural arch. Besides causing olisthesis, it is also capable of producing lysis of the pars especially if the dorsal spine has the added restraint of high tensile stresses in the posterior ligamentous system. Under normal conditions, the L5-S1 intervertebral joint is subject to the highest forces and it therefore receives the first damage. However, in the presence of antiverse process, damaging stress occurs in the next higher joint. While the antitorsional large transverse process may protect the L5-S1 joint from torsion, it may not protect the L5 vertebra from excessive flexional strains that may fracture the pars. Though lysis may occur in both instances, paradoxically spondylolysis and spondylolisthesis are mutually exclusive conditions. It has long been thought that shear force imbalance was the causative agent in olisthesis. This mechanism remains unconvincing except possibly in instances where there is a pathological condition affecting the skeletal tissue."} {"id": "PMID:1277686", "title": "Effect of lordosis on the stress in the lumbar spine.", "content": "A simple mathematical model is used to explore the influence of lordosis on the stress in the human spine. It is shown that flatter spines would tend to fail by flexion while spines with more lordosis would tend to fail by torsion.", "contents": "Effect of lordosis on the stress in the lumbar spine. A simple mathematical model is used to explore the influence of lordosis on the stress in the human spine. It is shown that flatter spines would tend to fail by flexion while spines with more lordosis would tend to fail by torsion."} {"id": "PMID:1277687", "title": "Mechanical factors in spondylolisthesis and spondylolysis.", "content": "Anterior displacement in spondylolisthesis is a slow process. The forces contributing to anterior shear arise from the vertical load on the spine above the lesion, from activity in the muscles of the spine and trunk, and from the effects of movements. The shear is normally resisted by the annulus fibrosus, compression of the facets at the apophyseal joints, and by tension in the anterolateral layers of cortical bone in the pars interarticularis. The anterior shear-strength of the disk is not known though Cyron and Hutton have shown that it is a major contributor to the total stiffness; in the early stages of spondylolysis it provides the only resistance. The capacity of the pars for resisting tensile forces anteriorly has been studied in tests of single vertebrae in which posterior forces were applied to the inferior articular processes. Forces at failure at L4 and L5 have been reported at up to 2500 N by Cyron et al. and up to 5800 N by Lamy et al. with means of 1800 N and 3200 N respectively. The mean posterior displacement of the inferior facets reported by Cyron et al. was 6.5 mm at failure. Too little is known of the mechanical factors in the etiology of spondylolysis for a definition of the postures and movements of the body which put the lumbar neural arch at greatest risk. While a combination of fatigue-failure and high strain-rate of forces induced in extended postures seems likely, further investigations are needed to elucidate the pathogenesis in many cases.", "contents": "Mechanical factors in spondylolisthesis and spondylolysis. Anterior displacement in spondylolisthesis is a slow process. The forces contributing to anterior shear arise from the vertical load on the spine above the lesion, from activity in the muscles of the spine and trunk, and from the effects of movements. The shear is normally resisted by the annulus fibrosus, compression of the facets at the apophyseal joints, and by tension in the anterolateral layers of cortical bone in the pars interarticularis. The anterior shear-strength of the disk is not known though Cyron and Hutton have shown that it is a major contributor to the total stiffness; in the early stages of spondylolysis it provides the only resistance. The capacity of the pars for resisting tensile forces anteriorly has been studied in tests of single vertebrae in which posterior forces were applied to the inferior articular processes. Forces at failure at L4 and L5 have been reported at up to 2500 N by Cyron et al. and up to 5800 N by Lamy et al. with means of 1800 N and 3200 N respectively. The mean posterior displacement of the inferior facets reported by Cyron et al. was 6.5 mm at failure. Too little is known of the mechanical factors in the etiology of spondylolysis for a definition of the postures and movements of the body which put the lumbar neural arch at greatest risk. While a combination of fatigue-failure and high strain-rate of forces induced in extended postures seems likely, further investigations are needed to elucidate the pathogenesis in many cases."} {"id": "PMID:1277688", "title": "Standing roentgenograms in spondylolisthesis.", "content": "Lateral roentgenograms of 50 patients with spondylolisthesis were made in the recumbent and standing positions and compared. Thirteen (26%) showed an increase in the percentage of displacement on standing. Those patients with demonstrable change appeared to have a higher incidence of severe symptomatology. Apparent spondylolysis on recumbent roentgenograms may change to spondylolisthesis on standing lateral roentgenograms. Degenerative spondylolisthesis may be more apparent on standing lateral roentgenograms.", "contents": "Standing roentgenograms in spondylolisthesis. Lateral roentgenograms of 50 patients with spondylolisthesis were made in the recumbent and standing positions and compared. Thirteen (26%) showed an increase in the percentage of displacement on standing. Those patients with demonstrable change appeared to have a higher incidence of severe symptomatology. Apparent spondylolysis on recumbent roentgenograms may change to spondylolisthesis on standing lateral roentgenograms. Degenerative spondylolisthesis may be more apparent on standing lateral roentgenograms."} {"id": "PMID:1277689", "title": "Operative treatment of spondylolisthesis in young patients.", "content": "In a series of 91 patients under 20 years of age with lytic spondylolisthesis treated by different operations, 66 (73%) showed a displacement of more than 30 per cent at admission. If the displacement exceeds 30 per cent, it often progresses to a subtotal olisthesis. Spinal fusion should be performed before the displacement exceeds a third of the length of the vertebra. A posterior fusion with two massive tibial grafts was carried out in 78 patients (87.5%). Concurrent with fusion laminectomy was performed in 18 patients. Anterior vertebral body fusion was performed in 3 patients and posterolateral fusion in 10, in 4 of these as a secondary operation. Laminectomy alone was carried out in 4 patients, 3 of these having a total olisthesis. Laminectomy without fusion should be performed only in exceptional cases in young patients. Non-union or uncertain union after the primary operations occurred in 17 cases (19.5%); 15 reoperations were performed in 13 patients. The degree of displacement at operation did not influence the results. A progression of displacement despite dorsal fusion was observed in 14 patients. The final results of operative treatment were: good in 55 patients (60.4%); satisfactory in 23 (24.1%); unsatisfactory in 13 (15.5%). Posterolateral fusion seems to be preferable to posterior fusion.", "contents": "Operative treatment of spondylolisthesis in young patients. In a series of 91 patients under 20 years of age with lytic spondylolisthesis treated by different operations, 66 (73%) showed a displacement of more than 30 per cent at admission. If the displacement exceeds 30 per cent, it often progresses to a subtotal olisthesis. Spinal fusion should be performed before the displacement exceeds a third of the length of the vertebra. A posterior fusion with two massive tibial grafts was carried out in 78 patients (87.5%). Concurrent with fusion laminectomy was performed in 18 patients. Anterior vertebral body fusion was performed in 3 patients and posterolateral fusion in 10, in 4 of these as a secondary operation. Laminectomy alone was carried out in 4 patients, 3 of these having a total olisthesis. Laminectomy without fusion should be performed only in exceptional cases in young patients. Non-union or uncertain union after the primary operations occurred in 17 cases (19.5%); 15 reoperations were performed in 13 patients. The degree of displacement at operation did not influence the results. A progression of displacement despite dorsal fusion was observed in 14 patients. The final results of operative treatment were: good in 55 patients (60.4%); satisfactory in 23 (24.1%); unsatisfactory in 13 (15.5%). Posterolateral fusion seems to be preferable to posterior fusion."} {"id": "PMID:1277690", "title": "Treatment of spondylolisthesis and spondylolysis in children.", "content": "There are 2 fairly common types of spondylolisthesis in children - dysplastic and isthmic. The dysplastic type is secondary to congenital defects at the lumbosacral joint. The isthmic is usually due to a fatigue fracture of the pars interarticularis but there is also an hereditary element in this type. Most children with spondylolisthesis never develop significant symptoms and even of those who do, the vast majority can be treated without surgery. If symptoms persist or if further olisthesis is occurring, a one-level spinal fusion done through a paraspinal approach is recommended. It is most important not to allow olisthesis to develop to the point that the child shows the cosmetically undesirable stigmata characteristic of the condition. Solid fusion can be obtained in every case and will stop further slip.", "contents": "Treatment of spondylolisthesis and spondylolysis in children. There are 2 fairly common types of spondylolisthesis in children - dysplastic and isthmic. The dysplastic type is secondary to congenital defects at the lumbosacral joint. The isthmic is usually due to a fatigue fracture of the pars interarticularis but there is also an hereditary element in this type. Most children with spondylolisthesis never develop significant symptoms and even of those who do, the vast majority can be treated without surgery. If symptoms persist or if further olisthesis is occurring, a one-level spinal fusion done through a paraspinal approach is recommended. It is most important not to allow olisthesis to develop to the point that the child shows the cosmetically undesirable stigmata characteristic of the condition. Solid fusion can be obtained in every case and will stop further slip."} {"id": "PMID:1277693", "title": "Hemolytic anemia and edema as the initial signs in infants with cystic fibrosis. Consider this diagnosis even in absence of pulmonary symptoms.", "content": "This is a report of five infants eventually proven to have cystic fibrosis of the pancreas, who presented with hemolytic anemia and edema. Since the sweat test is often unreliable in edematous states, the possibility of cystic fibrosis should be considered. Use of either a protein hydrolysate or addition of pancreatic enzymes will improve nutritional status, and when edema disappears, a definite sweat test can be performed. Evidence of vitamin E deficiency in some of the cases is presented, and the possibility of this as a cause of anemia is raised.", "contents": "Hemolytic anemia and edema as the initial signs in infants with cystic fibrosis. Consider this diagnosis even in absence of pulmonary symptoms. This is a report of five infants eventually proven to have cystic fibrosis of the pancreas, who presented with hemolytic anemia and edema. Since the sweat test is often unreliable in edematous states, the possibility of cystic fibrosis should be considered. Use of either a protein hydrolysate or addition of pancreatic enzymes will improve nutritional status, and when edema disappears, a definite sweat test can be performed. Evidence of vitamin E deficiency in some of the cases is presented, and the possibility of this as a cause of anemia is raised."} {"id": "PMID:1277696", "title": "The susceptibility of adolescent girls to rubella. Observations on 297 girls in Toronto.", "content": "Since serum rubella H-I antibody titers of 297 adolescent girls showed 25.3 per cent to be susceptible, we support the recommendation that all susceptible girls be immunized, provided of course that after individual evaluation there is no risk of pregnancy at the time of immunization or in the ensuing two months.", "contents": "The susceptibility of adolescent girls to rubella. Observations on 297 girls in Toronto. Since serum rubella H-I antibody titers of 297 adolescent girls showed 25.3 per cent to be susceptible, we support the recommendation that all susceptible girls be immunized, provided of course that after individual evaluation there is no risk of pregnancy at the time of immunization or in the ensuing two months."} {"id": "PMID:1277700", "title": "Lead on painted handles of kitchen utensils.", "content": "The lead content of paint on wooden handles of kitchen utensils ranged from 0 to 9.7 per cent (97,000 ppm). Yellow paint showed the highest concentration of lead followed by green and red colors. The values of lead often exceeded the legal limit on toys and paint for use indoors.", "contents": "Lead on painted handles of kitchen utensils. The lead content of paint on wooden handles of kitchen utensils ranged from 0 to 9.7 per cent (97,000 ppm). Yellow paint showed the highest concentration of lead followed by green and red colors. The values of lead often exceeded the legal limit on toys and paint for use indoors."} {"id": "PMID:1277705", "title": "Adverse drug reactions-a matter of opinion.", "content": "The accurate identification of adverse drug reactions (ADRs) is difficult because ADRs usually present no unique clinical or laboratory findings that demarcate them from the manifestations of concurrent illnesses. The identification of ADRs depends on the clinical assessments of physicians-sometimes the clinician treating the patient and at other times a clinical pharmacologist. Considering the complex and subjective nature of clinically identifying ADRs, how accurately are ADRs identified? To answer this question, three clinical pharmacologists each independently evaluated 60 selected cases to determine if medication, alcohol, or \"recreational\" drugs had caused the hospitalization. The three clinical pharmacologists agreed on only 30 cases (50%), and 27 of these were thought to be unrelated to medications. In 19 of the 30 cases about which the clinical pharmacologists disagreed, they disagreed on whether or not a medication-or alcohol-related event had occurred at all. The clinical pharmacologists disagreed with the physicians treating the patient in 22% to 37% of the cases, but because of the differences among the pharmacologists, the treating physicians agreed with at least one of them in 95% of the cases. Complete agreement between the clinical pharmacologists and the treating physicians occurred in 47% of the cases. This degree of disparity in the clinical identification of ADRs shows that the evaluation of ADRs is subjective and imprecise. The accurate identification of ADRs awaits the development of an objective technique for recognizing ADRs.", "contents": "Adverse drug reactions-a matter of opinion. The accurate identification of adverse drug reactions (ADRs) is difficult because ADRs usually present no unique clinical or laboratory findings that demarcate them from the manifestations of concurrent illnesses. The identification of ADRs depends on the clinical assessments of physicians-sometimes the clinician treating the patient and at other times a clinical pharmacologist. Considering the complex and subjective nature of clinically identifying ADRs, how accurately are ADRs identified? To answer this question, three clinical pharmacologists each independently evaluated 60 selected cases to determine if medication, alcohol, or \"recreational\" drugs had caused the hospitalization. The three clinical pharmacologists agreed on only 30 cases (50%), and 27 of these were thought to be unrelated to medications. In 19 of the 30 cases about which the clinical pharmacologists disagreed, they disagreed on whether or not a medication-or alcohol-related event had occurred at all. The clinical pharmacologists disagreed with the physicians treating the patient in 22% to 37% of the cases, but because of the differences among the pharmacologists, the treating physicians agreed with at least one of them in 95% of the cases. Complete agreement between the clinical pharmacologists and the treating physicians occurred in 47% of the cases. This degree of disparity in the clinical identification of ADRs shows that the evaluation of ADRs is subjective and imprecise. The accurate identification of ADRs awaits the development of an objective technique for recognizing ADRs."} {"id": "PMID:1277706", "title": "Effect of lidocaine on right ventricular muscle refractoriness.", "content": "The effect of clinical doses of lidocaine on ventricular refractoriness was investigated in man. Effective refractory period (ERP) and functional refractory period (FRP) were determined in 11 normokalemic patients via a catheter at the right ventricular apex using programmed extra-stimuli and a ventricular electrogram recorded from the pacing catheter. No subject had recent ischemia or infarction. Measurements were repeated after clinical doses of lidocaine that produced therapeutic blood levels. Lidocaine caused no significant change in ERP or FRP during ventricular or atrial drive, or sinus rhythm with unchanged cycle length (CL). During sinus rhythm ERP/CL was unchanged. In 4 of 5 patients, lidocaine did not abolish echo phenomena observed during ventricular drive. This study demonstrates that ventricular refractoriness can be safely measured in man. Clinical doses of lidocaine did not alter right ventricular refractory periods. Lidocaine action is not explained by alteration of ventricular refractoriness, at least in muscle remote from the site of acute infarction.", "contents": "Effect of lidocaine on right ventricular muscle refractoriness. The effect of clinical doses of lidocaine on ventricular refractoriness was investigated in man. Effective refractory period (ERP) and functional refractory period (FRP) were determined in 11 normokalemic patients via a catheter at the right ventricular apex using programmed extra-stimuli and a ventricular electrogram recorded from the pacing catheter. No subject had recent ischemia or infarction. Measurements were repeated after clinical doses of lidocaine that produced therapeutic blood levels. Lidocaine caused no significant change in ERP or FRP during ventricular or atrial drive, or sinus rhythm with unchanged cycle length (CL). During sinus rhythm ERP/CL was unchanged. In 4 of 5 patients, lidocaine did not abolish echo phenomena observed during ventricular drive. This study demonstrates that ventricular refractoriness can be safely measured in man. Clinical doses of lidocaine did not alter right ventricular refractory periods. Lidocaine action is not explained by alteration of ventricular refractoriness, at least in muscle remote from the site of acute infarction."} {"id": "PMID:1277707", "title": "Serum triiodothyronine levels in patients receiving L-thyroxine.", "content": "Serum triiodothyronine (T3) and thyroxine (T4) levels were measured in 103 adult patients receiving sodium L-thyroxine (Synthroid), 0.2 or 0.3 mg daily for at least 3 mo, as suppression or replacement therapy. All were judged to be clinically euthyroid at the time of the measurements. The mean +/-SD T3 level during treatment was 130.3 +/-47.5 ng% and the mean T4 level was 11.0 +/-2.0 mug%. In normal untreated euthyroid subjects, the mean T3 level was 115.4 +/-26.0 ng% and the mean T4 level was 8.0 +/-1.7mug%. When sodium L-thyroxine was added in vitro to the stored sera of 10 hypothyroid patients to produce serum T4 levels equivalent to those that the patients later showed in vivo while on therapy, the cross-reaction was 0.85%. Thus at a mean T4 level of 11.0 mug%, there was a mean T3 level of 93.5 ng% that could be attributed to the added thyroxine itself. This cross-reaction was found to be due to contamination of the added sodium L-thyroxine with T3 and not due to cross-reactivity of the T3 antibody in the immunoassay system with T4. For 3 other brands of sodium L-thyroxine, the T3 contamination of the added T4 was 0.75%, 0.55%, and 0.40%. When 6 hypothyroid patients were given 5 mug of L-triiodothyronine (Cytomel) daily for 4 wk, there was no rise in serum T3 levels. When the same patients were switched to sodium L-thyroxine, 0.2 mg daily, serum T3 levels rose from a mean +/-SD of 60.0 +/-16.3 ng% to a mean of 130.0 +/-38.0 ng%. It would thus appear that in patients receiving sodium L-throxine therapy, the resulting serum T3 levels are due to extrathyroidal conversion of the administered T4 to T3, and not to the T3 present in the L-thyroxine administered.", "contents": "Serum triiodothyronine levels in patients receiving L-thyroxine. Serum triiodothyronine (T3) and thyroxine (T4) levels were measured in 103 adult patients receiving sodium L-thyroxine (Synthroid), 0.2 or 0.3 mg daily for at least 3 mo, as suppression or replacement therapy. All were judged to be clinically euthyroid at the time of the measurements. The mean +/-SD T3 level during treatment was 130.3 +/-47.5 ng% and the mean T4 level was 11.0 +/-2.0 mug%. In normal untreated euthyroid subjects, the mean T3 level was 115.4 +/-26.0 ng% and the mean T4 level was 8.0 +/-1.7mug%. When sodium L-thyroxine was added in vitro to the stored sera of 10 hypothyroid patients to produce serum T4 levels equivalent to those that the patients later showed in vivo while on therapy, the cross-reaction was 0.85%. Thus at a mean T4 level of 11.0 mug%, there was a mean T3 level of 93.5 ng% that could be attributed to the added thyroxine itself. This cross-reaction was found to be due to contamination of the added sodium L-thyroxine with T3 and not due to cross-reactivity of the T3 antibody in the immunoassay system with T4. For 3 other brands of sodium L-thyroxine, the T3 contamination of the added T4 was 0.75%, 0.55%, and 0.40%. When 6 hypothyroid patients were given 5 mug of L-triiodothyronine (Cytomel) daily for 4 wk, there was no rise in serum T3 levels. When the same patients were switched to sodium L-thyroxine, 0.2 mg daily, serum T3 levels rose from a mean +/-SD of 60.0 +/-16.3 ng% to a mean of 130.0 +/-38.0 ng%. It would thus appear that in patients receiving sodium L-throxine therapy, the resulting serum T3 levels are due to extrathyroidal conversion of the administered T4 to T3, and not to the T3 present in the L-thyroxine administered."} {"id": "PMID:1277708", "title": "Absorption, metabolism, and excretion of hydrochlorothiazide.", "content": "14C-hydrochlorothiazide (hct) was administered orally (n=4) and iv (n = 2 to healthy subjects. The gastrointestinal absorption ranged between 60% and 80%, most of it took place in the duodenum and the upper jejunum. The radioactivity was eliminated mainly in the urine, while no sigificant biliary excretion was observed. Chromatographic analysis of the urinary radioactivity demonstrated that greater than 95% of the absorbed or injected 14C-hct was excreted unchanged. The radioactivity in plasma during the first 10 hr after oral administration declined with a fast phase but the levels of label thereafter suggested a slow phase. The existence of such a phase was verified in 1 subject given 75 mg hct orally. His plasma levels of hct (determined with gas-liquid chromatography) declined according to a 2-compartment model, the half-lives of the alpha-and beta-phases being 1.7 and 13.1 hr, respectively. Hct accumulated in the blood cells and the ratio between the radioactivity in cells and that in plasma averaged 3.5. The fate of a single dose of 14C-hct in 2 hypertensive patients treated with the drug chronically was similar to that in the healthy subjects. A third patient, who had slightly elevated serum creatinine, eliminated hct more slowly than the others. Like the healthy subjects, the patients eliminated hct to greater than 95% in unchanged form.", "contents": "Absorption, metabolism, and excretion of hydrochlorothiazide. 14C-hydrochlorothiazide (hct) was administered orally (n=4) and iv (n = 2 to healthy subjects. The gastrointestinal absorption ranged between 60% and 80%, most of it took place in the duodenum and the upper jejunum. The radioactivity was eliminated mainly in the urine, while no sigificant biliary excretion was observed. Chromatographic analysis of the urinary radioactivity demonstrated that greater than 95% of the absorbed or injected 14C-hct was excreted unchanged. The radioactivity in plasma during the first 10 hr after oral administration declined with a fast phase but the levels of label thereafter suggested a slow phase. The existence of such a phase was verified in 1 subject given 75 mg hct orally. His plasma levels of hct (determined with gas-liquid chromatography) declined according to a 2-compartment model, the half-lives of the alpha-and beta-phases being 1.7 and 13.1 hr, respectively. Hct accumulated in the blood cells and the ratio between the radioactivity in cells and that in plasma averaged 3.5. The fate of a single dose of 14C-hct in 2 hypertensive patients treated with the drug chronically was similar to that in the healthy subjects. A third patient, who had slightly elevated serum creatinine, eliminated hct more slowly than the others. Like the healthy subjects, the patients eliminated hct to greater than 95% in unchanged form."} {"id": "PMID:1277709", "title": "Furosemide and bumetanide: a study of responses in normal English and German subjects.", "content": "Diuretic responses to oral administration of 1 mg bumetanide and 40 mg furosemide were determined in double-blind, crossover balanced trials in 10 normal English subjects and 6 normal German subjects. In each experiment the 0- to 8-hr urine volume and sodium excretion were significantly higher after bumetanide, potassium excretion did not differ, and the Na/K ratio, although higher after bumetanide, was not significantly different by analysis of variance. In German subjects the diuretic and natriuretic responses to both drugs were greater and the potassium excretion less than in English subjects. In the English, the pretreatment 24-hr urinary Na/K ratio correlated with the urinary Na/K ratio response to both drugs and with the potassium excretion after furosemide. The mean plasma uric acid before treatment correlated with the Na/K ratio and potassium excretion after furosemide. Aldosterone excretion did not correlate with response to either diuretic. The mean pretreatment 24-hr log10 Na/K ratio in the two treatment periods of the English and German subjects correlated with the mean sodium excretion, potassium excretion, and log10 Na/K after the two diuretics, thus providing a partial explanation for intersubject and interstudy variation. Pretreatment log10 Na/K could also explain intrasubject variation, justifying its use as a covariate in covariance analysis. This demonstrated that at this dose ratio the urinary log10 Na/K ratio response to bumetanide was significantly higher than that to furosemide.", "contents": "Furosemide and bumetanide: a study of responses in normal English and German subjects. Diuretic responses to oral administration of 1 mg bumetanide and 40 mg furosemide were determined in double-blind, crossover balanced trials in 10 normal English subjects and 6 normal German subjects. In each experiment the 0- to 8-hr urine volume and sodium excretion were significantly higher after bumetanide, potassium excretion did not differ, and the Na/K ratio, although higher after bumetanide, was not significantly different by analysis of variance. In German subjects the diuretic and natriuretic responses to both drugs were greater and the potassium excretion less than in English subjects. In the English, the pretreatment 24-hr urinary Na/K ratio correlated with the urinary Na/K ratio response to both drugs and with the potassium excretion after furosemide. The mean plasma uric acid before treatment correlated with the Na/K ratio and potassium excretion after furosemide. Aldosterone excretion did not correlate with response to either diuretic. The mean pretreatment 24-hr log10 Na/K ratio in the two treatment periods of the English and German subjects correlated with the mean sodium excretion, potassium excretion, and log10 Na/K after the two diuretics, thus providing a partial explanation for intersubject and interstudy variation. Pretreatment log10 Na/K could also explain intrasubject variation, justifying its use as a covariate in covariance analysis. This demonstrated that at this dose ratio the urinary log10 Na/K ratio response to bumetanide was significantly higher than that to furosemide."} {"id": "PMID:1277710", "title": "Effect of smoking on theophylline disposition.", "content": "The pharmacokinetics of theophylline were examined in a group of nonsmokers and in heavy smokers (1 to 2 packs/day) before and 3 to 4 mo after cessation of cigarette smoking. The half-life of theophylline in smokers averaged 4.3 (SD = 1.4) hr, significantly shorter than the mean value in nonsmokers (7.0, SD =1.7 hr). The apparent volume of distribution of theophylline was somewhat larger in smokers (0.50 +/-0.12 L/kg) than in nonsmokers (0.38 +/-0.04 L/kg). The body clearance of theophylline was appreciably larger and relatively more variable in smokers (100 +/-44 ml/min/1.73 m2) than in nonsmokers (45 +/-13 ml/min/1.73 m2). Serum concentrations of thiocyanate, a biotransformation product of cyanide which is inhaled with smoke, were used to monitor the smoking status of the subjects. The body clearances of theophylline showed a good correlation (r = 0.785, p less than 0.001) with the serum thiocyanate concentrations. Of the 8 smokers, only 4 managed to refrain from smoking for at least 3 mo, and these subjects showed no significant change in theophylline elimination. The increase in theophylline clearance caused by smoking is probably the result of induction of drug-metabolizing enzymes that do not readily normalize after cessation of smoking.", "contents": "Effect of smoking on theophylline disposition. The pharmacokinetics of theophylline were examined in a group of nonsmokers and in heavy smokers (1 to 2 packs/day) before and 3 to 4 mo after cessation of cigarette smoking. The half-life of theophylline in smokers averaged 4.3 (SD = 1.4) hr, significantly shorter than the mean value in nonsmokers (7.0, SD =1.7 hr). The apparent volume of distribution of theophylline was somewhat larger in smokers (0.50 +/-0.12 L/kg) than in nonsmokers (0.38 +/-0.04 L/kg). The body clearance of theophylline was appreciably larger and relatively more variable in smokers (100 +/-44 ml/min/1.73 m2) than in nonsmokers (45 +/-13 ml/min/1.73 m2). Serum concentrations of thiocyanate, a biotransformation product of cyanide which is inhaled with smoke, were used to monitor the smoking status of the subjects. The body clearances of theophylline showed a good correlation (r = 0.785, p less than 0.001) with the serum thiocyanate concentrations. Of the 8 smokers, only 4 managed to refrain from smoking for at least 3 mo, and these subjects showed no significant change in theophylline elimination. The increase in theophylline clearance caused by smoking is probably the result of induction of drug-metabolizing enzymes that do not readily normalize after cessation of smoking."} {"id": "PMID:1277711", "title": "Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect.", "content": "The serum protein binding and elimination kinetics of warfarin were determined in 31 patients with cardiovascular disease who were taking warfarin regularly. The free fraction of warfarin in the serum ranged from 0.00436 to 0.0189, indicating 98.11% to 99.56% protein binding. There was no apparent relationship between the extent of protein binding of warfarin and the concentration of albumin or total protein in the serum. The estimated total body clearance of warfarin in the patients ranged from 1.16 to 4.35ml/hr/kg of body weight and correlated significantly with the free fraction of warfarin in serum. This correlation has been predicted on theoretical grounds and shows that serum protein binding is a major determinant of the elimination kinetics of warfarin in man and an important cause of interindividual variations in its body clearance. The interindividual variation of free warfarin concentrations in the serum of patients with similar prothrombin times was somewhat smaller than the variations in total serum-warfarin concentrations and in the daily dose of warfarin. There was no correlation between prothrombin time and the concentration of free warfarin in serum, indicating that variables other than protein binding also affect the anticoagulant response of patients.", "contents": "Serum protein binding as a determinant of warfarin body clearance and anticoagulant effect. The serum protein binding and elimination kinetics of warfarin were determined in 31 patients with cardiovascular disease who were taking warfarin regularly. The free fraction of warfarin in the serum ranged from 0.00436 to 0.0189, indicating 98.11% to 99.56% protein binding. There was no apparent relationship between the extent of protein binding of warfarin and the concentration of albumin or total protein in the serum. The estimated total body clearance of warfarin in the patients ranged from 1.16 to 4.35ml/hr/kg of body weight and correlated significantly with the free fraction of warfarin in serum. This correlation has been predicted on theoretical grounds and shows that serum protein binding is a major determinant of the elimination kinetics of warfarin in man and an important cause of interindividual variations in its body clearance. The interindividual variation of free warfarin concentrations in the serum of patients with similar prothrombin times was somewhat smaller than the variations in total serum-warfarin concentrations and in the daily dose of warfarin. There was no correlation between prothrombin time and the concentration of free warfarin in serum, indicating that variables other than protein binding also affect the anticoagulant response of patients."} {"id": "PMID:1277712", "title": "Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levels.", "content": "The influence of various test meals and ingested fluid volumes on the bioavailability and pharmacokinetics of propoxyphene and its major metabolite norporpoxyphene has been studied in healthy human subjects. The absorption of drug was delayed by all test meals, but the overall efficiency of absorption was either not affected or was slightly increased. Increased fluid volume intake decreased propoxyphene bioavailability. Plasma levels of metabolite correlated well with levels of unchanged drug, particularly in the first 2 hr after dosing, but were not markedly influenced by treatments.", "contents": "Propoxyphene and norpropoxyphene: influence of diet and fluid on plasma levels. The influence of various test meals and ingested fluid volumes on the bioavailability and pharmacokinetics of propoxyphene and its major metabolite norporpoxyphene has been studied in healthy human subjects. The absorption of drug was delayed by all test meals, but the overall efficiency of absorption was either not affected or was slightly increased. Increased fluid volume intake decreased propoxyphene bioavailability. Plasma levels of metabolite correlated well with levels of unchanged drug, particularly in the first 2 hr after dosing, but were not markedly influenced by treatments."} {"id": "PMID:1277713", "title": "Disposition kinetics of two oral forms of quinidine.", "content": "There are relatively few studies on the disposition properties of quinidine. We have studied in 10 normal subjects conventional quinidine sulfate and a slow-release quinidine bisulfate. Single and repetitive doses were given; blood and urine concentrations were measured by the method of Cramer and Isaakson. After a single dose of two tablets of quinidine sulfate (400 mg), the average peak concentration was 2.13 +/-0.22 mug/ml (+/-SEM); following two tablets of the slow-release form, the average peak concentration was 1.17 +/-0.12 mug/ml. T-max was approximately 2 hr with quinidine sulfate and 4 hr with quinidine bisulfate. One fourth of both forms of the drug was recovered in the urine. Total body clearance was 0.36 L/kg-hr and renal clearance was 117 +/-22ml/min for both. With multiple dosing the serum quinidine concentration was higher than these predicted from the results of the single-dose study. Based on the mean estimates of quinidine half-life of 6 hr, a rapid method for achieving steady-state levels of quinidine would be to give an initial dose twice that of the maintenance dose. With the slow-release product if an equivalent dose was given every 12 hr, the mean steady-state quinidine serum concentration would be approximately the same.", "contents": "Disposition kinetics of two oral forms of quinidine. There are relatively few studies on the disposition properties of quinidine. We have studied in 10 normal subjects conventional quinidine sulfate and a slow-release quinidine bisulfate. Single and repetitive doses were given; blood and urine concentrations were measured by the method of Cramer and Isaakson. After a single dose of two tablets of quinidine sulfate (400 mg), the average peak concentration was 2.13 +/-0.22 mug/ml (+/-SEM); following two tablets of the slow-release form, the average peak concentration was 1.17 +/-0.12 mug/ml. T-max was approximately 2 hr with quinidine sulfate and 4 hr with quinidine bisulfate. One fourth of both forms of the drug was recovered in the urine. Total body clearance was 0.36 L/kg-hr and renal clearance was 117 +/-22ml/min for both. With multiple dosing the serum quinidine concentration was higher than these predicted from the results of the single-dose study. Based on the mean estimates of quinidine half-life of 6 hr, a rapid method for achieving steady-state levels of quinidine would be to give an initial dose twice that of the maintenance dose. With the slow-release product if an equivalent dose was given every 12 hr, the mean steady-state quinidine serum concentration would be approximately the same."} {"id": "PMID:1277714", "title": "Intestinal absorption, demethylation, and enterohepatic circulation of imipramine.", "content": "The intestinal absorption and metabolism of single oral doses of imipramine (ip) have been studied in man by portal catheterization. The concentration of ip and the formed desipramine (dmi) was followed in blood-plasma obtained from the portal and cubital veins. The absorption of ip seemed to be completed 80 min after the administration of the drug. There was no sign of demethylation of ip during the passage across the intestinal wall. Evidence was found of an enterohepatic circulation of both ip and dmi.", "contents": "Intestinal absorption, demethylation, and enterohepatic circulation of imipramine. The intestinal absorption and metabolism of single oral doses of imipramine (ip) have been studied in man by portal catheterization. The concentration of ip and the formed desipramine (dmi) was followed in blood-plasma obtained from the portal and cubital veins. The absorption of ip seemed to be completed 80 min after the administration of the drug. There was no sign of demethylation of ip during the passage across the intestinal wall. Evidence was found of an enterohepatic circulation of both ip and dmi."} {"id": "PMID:1277715", "title": "Pivampicillin and ampicillin in bile, portal and peripheral blood.", "content": "In 7 patients with a catheter in the portal vein and a T tube in the common bile duct, the concentration of unhydrolyzed pivampicillin and of ampicillin was measured simultaneously in portal and peripheral blood and in bile after oral administration of 700 mg pivampicillin. In both portal and peripheral circulation of concentration of unhydrolyzed pivampicillin was always less than 1% of the levels of ampicillin, indicating the effectiveness of the intestinal mucosa in the hydrolysis of pivampicillin. Evidence for the ability of the liver to excrete ampicillin against a concentration gradient into the bile was established by direct measurements. Only about 1% of the dose given could be recovered in the bile. There was an unexplained reduction of about 70% in the absorption of the drug induced by the catheter itself.", "contents": "Pivampicillin and ampicillin in bile, portal and peripheral blood. In 7 patients with a catheter in the portal vein and a T tube in the common bile duct, the concentration of unhydrolyzed pivampicillin and of ampicillin was measured simultaneously in portal and peripheral blood and in bile after oral administration of 700 mg pivampicillin. In both portal and peripheral circulation of concentration of unhydrolyzed pivampicillin was always less than 1% of the levels of ampicillin, indicating the effectiveness of the intestinal mucosa in the hydrolysis of pivampicillin. Evidence for the ability of the liver to excrete ampicillin against a concentration gradient into the bile was established by direct measurements. Only about 1% of the dose given could be recovered in the bile. There was an unexplained reduction of about 70% in the absorption of the drug induced by the catheter itself."} {"id": "PMID:1277718", "title": "Anorectal pruritus after intravenous hydrocortisone sodium succinate and sodium phosphate.", "content": "A double-blind study demonstrated that single intravenous doses of 100, 200, or 400 mg of hydrocortisone sodium succinate and hydrocortisone sodium phosphate were similar in eosinophil suppression, elevation of glucose, white blood count differential shifts (polymorphonuclear cells, lymphocytes, and monocytes), and urinary excretion of sodium and potassium but not in incidence of side effects. More subjects receiving hydrocortisone sodium phosphate experienced systemic or localized adverse effects than those receiving hydrocortisone sodium succinate. The most common side effect was burning or itching in the anorectal area, which occurred in 16 of 18 subjects medicated with hydrocortisone sodium phosphate, in 1 subject of 6 treated with placebo (saline), and in none who received the sodium succinate. The effect is attributed to the phosphate steroid and appears to last as long as it takes to convert to cortisol.", "contents": "Anorectal pruritus after intravenous hydrocortisone sodium succinate and sodium phosphate. A double-blind study demonstrated that single intravenous doses of 100, 200, or 400 mg of hydrocortisone sodium succinate and hydrocortisone sodium phosphate were similar in eosinophil suppression, elevation of glucose, white blood count differential shifts (polymorphonuclear cells, lymphocytes, and monocytes), and urinary excretion of sodium and potassium but not in incidence of side effects. More subjects receiving hydrocortisone sodium phosphate experienced systemic or localized adverse effects than those receiving hydrocortisone sodium succinate. The most common side effect was burning or itching in the anorectal area, which occurred in 16 of 18 subjects medicated with hydrocortisone sodium phosphate, in 1 subject of 6 treated with placebo (saline), and in none who received the sodium succinate. The effect is attributed to the phosphate steroid and appears to last as long as it takes to convert to cortisol."} {"id": "PMID:1277722", "title": "Studies on digitalis. VI. The effect of heparin on serum protein binding of digitoxin and digoxin.", "content": "The aim of the present study was to investigate the nature of the previously reported changes in the serum protein binding of digitoxin and digoxin in uremic patients under treatment with hemodialysis. Kinetic studies on protein binding during hemodialysis showed that the free fraction of digitoxin rose from 2.6% to 6.9% after 5 min of hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from 78.3% to 87.1% during the same period. In vitro hemodialysis experiments showed that such changes occurred only in vivo. Injection of heparin (5,000 IU) to control subjects produced similar kinetic changes in the protein binding of digitoxin and digoxin. Free fatty acids changed in the same way. These results indicate that the heparin-induced release of free fatty acids causes displacement of digitoxin and digoxin from their albumin-binding sites. Patients on hemodialysis have lower serum levels of digitoxin and cardioactive metabolites (mean, 8.9 ng/ml) than control patients (mean, 16.7 ng/ml) (p less than 0.005) on similar doses (mean, 0.085 mg/day). They should be maintained on the same digotoxin doses as uremic and control patients, but serum digitoxin levels should be adjusted to 10 to 15 ng/ml in hemodialysis patients compared to 15 to 25 ng/ml in uremic patients and in patients with normal renal function.", "contents": "Studies on digitalis. VI. The effect of heparin on serum protein binding of digitoxin and digoxin. The aim of the present study was to investigate the nature of the previously reported changes in the serum protein binding of digitoxin and digoxin in uremic patients under treatment with hemodialysis. Kinetic studies on protein binding during hemodialysis showed that the free fraction of digitoxin rose from 2.6% to 6.9% after 5 min of hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from hemodialysis and remained elevated during the dialyzing period. Free digoxin rose from 78.3% to 87.1% during the same period. In vitro hemodialysis experiments showed that such changes occurred only in vivo. Injection of heparin (5,000 IU) to control subjects produced similar kinetic changes in the protein binding of digitoxin and digoxin. Free fatty acids changed in the same way. These results indicate that the heparin-induced release of free fatty acids causes displacement of digitoxin and digoxin from their albumin-binding sites. Patients on hemodialysis have lower serum levels of digitoxin and cardioactive metabolites (mean, 8.9 ng/ml) than control patients (mean, 16.7 ng/ml) (p less than 0.005) on similar doses (mean, 0.085 mg/day). They should be maintained on the same digotoxin doses as uremic and control patients, but serum digitoxin levels should be adjusted to 10 to 15 ng/ml in hemodialysis patients compared to 15 to 25 ng/ml in uremic patients and in patients with normal renal function."} {"id": "PMID:1277723", "title": "Cardiovascular effects of a new inotropic drug in dog and normal man.", "content": "Cardiovascular effects of 1-butyl-3(1-(6,7-dimethoxyquinazolin-4-yl) piperidin 4 yl urea) (BDPU) were studied in 16 anesthetized dogs and in 7 healthy male volunteers. In animal experiments intravenous doses of 100, 250, and 500 mug/kg/min produced dose-related, significant increases in cardiac output and peak left ventricular dp/dt. No changes in heart rate and blood pressure occurred at 100 mug/kg/min, whereas higher doses caused falls in both systolic and diastolic blood pressures, accompanied by significant rises in heart rate. Inotropic effects could also be demonstrated in man. Changes of the systolic time intervals were dose-related and began at 64 mug/kg/min. At 250 mug/kg/min, the highest dose administered, the pre-ejection period decreased by 14.8 +/- 4.42 msec and its ratio with left ventricular ejection time by 0.049 +/- 0.017 against their respective control values (p less than 0.01). In contrast to animal experiments, no hypotension or tachycardia was observed in any subject. Pharmacokinetic studies showed a plasma elimination half-life of 76 +/- 3 min (mean +/- SE). There were no subjective side effects and standard laboratory tests were not altered, but there was a slight but significant rise in the urinary enzymes, lactic dehydrogenase (LDH) and glutamic oxaloacetic transaminase (GOT), which persisted up to 7 days.", "contents": "Cardiovascular effects of a new inotropic drug in dog and normal man. Cardiovascular effects of 1-butyl-3(1-(6,7-dimethoxyquinazolin-4-yl) piperidin 4 yl urea) (BDPU) were studied in 16 anesthetized dogs and in 7 healthy male volunteers. In animal experiments intravenous doses of 100, 250, and 500 mug/kg/min produced dose-related, significant increases in cardiac output and peak left ventricular dp/dt. No changes in heart rate and blood pressure occurred at 100 mug/kg/min, whereas higher doses caused falls in both systolic and diastolic blood pressures, accompanied by significant rises in heart rate. Inotropic effects could also be demonstrated in man. Changes of the systolic time intervals were dose-related and began at 64 mug/kg/min. At 250 mug/kg/min, the highest dose administered, the pre-ejection period decreased by 14.8 +/- 4.42 msec and its ratio with left ventricular ejection time by 0.049 +/- 0.017 against their respective control values (p less than 0.01). In contrast to animal experiments, no hypotension or tachycardia was observed in any subject. Pharmacokinetic studies showed a plasma elimination half-life of 76 +/- 3 min (mean +/- SE). There were no subjective side effects and standard laboratory tests were not altered, but there was a slight but significant rise in the urinary enzymes, lactic dehydrogenase (LDH) and glutamic oxaloacetic transaminase (GOT), which persisted up to 7 days."} {"id": "PMID:1277724", "title": "Impaired plasma protein binding of phenytoin in uremia and displacement effect of salicylic acid.", "content": "The plasma protein binding of phenytoin (DPH) was studied by equilibrium dialysis at 37 degrees C in plasma from uremic patients and healthy subjects. Scatchard plot analyses demonstrated a decreased association constant Ka for the DPH-albumin interaction in the uremic plasma (mean 1.76 - 10(3) M-1 +/-SD 0.12 and a mean 4.10 - 10(3) M-1 +/- SD 0.24 in normal plasma). Studies on separated fractions of serum did not indicate any significant binding of DPH to proteins other than albumin. The nonlinear mathematical relationship between bound DPH and serum albumin could be linearized at low drug concentrations by plotting the ratio of bound/unbound DPH against albumin concentration. The displacement effect of salicylic acid at a concentration of 276 mug/ml (2mM) and DPH was considerable in plasma from normal subjects. In uremic plasma the effect was of much smaller magnitude.", "contents": "Impaired plasma protein binding of phenytoin in uremia and displacement effect of salicylic acid. The plasma protein binding of phenytoin (DPH) was studied by equilibrium dialysis at 37 degrees C in plasma from uremic patients and healthy subjects. Scatchard plot analyses demonstrated a decreased association constant Ka for the DPH-albumin interaction in the uremic plasma (mean 1.76 - 10(3) M-1 +/-SD 0.12 and a mean 4.10 - 10(3) M-1 +/- SD 0.24 in normal plasma). Studies on separated fractions of serum did not indicate any significant binding of DPH to proteins other than albumin. The nonlinear mathematical relationship between bound DPH and serum albumin could be linearized at low drug concentrations by plotting the ratio of bound/unbound DPH against albumin concentration. The displacement effect of salicylic acid at a concentration of 276 mug/ml (2mM) and DPH was considerable in plasma from normal subjects. In uremic plasma the effect was of much smaller magnitude."} {"id": "PMID:1277725", "title": "Kinetics and dose calculations of amikacin in the newborn.", "content": "The pharmacokinetics of a new aminoglycoside, amikacin, was evaluated in 37 infants between 1 and 34 days old. Fifteen were below 2,500 gm in weight. Initial studies, including intravenous infusion in some of the infants, indicated that the disposition of amikacin was best described by a 2 compartment model. The absorption was evaluated in 8 of the infants after intramuscular injection of 7.5 mg amikacin per kilogram of body weight. The absorption rate, estimated by the tmax, was significantly faster than reported in adults. The total body clearance and apparent volume of distribution were studied in 22 infants after the same dose of amikacin intramuscularly. The body clearance expressed in relation to body surface or body weight was significantly less than in adults and correlated with the postnatal age. No correlation could be demonstrated between clearance and gestational age or birth weight. The volume of distribution per kilogram was significantly greater than in adults. On the basis of the derived kinetic parameters, a dose schedule is presented. In 5 children there was a reasonable agreement between the measured and predicted serum levels.", "contents": "Kinetics and dose calculations of amikacin in the newborn. The pharmacokinetics of a new aminoglycoside, amikacin, was evaluated in 37 infants between 1 and 34 days old. Fifteen were below 2,500 gm in weight. Initial studies, including intravenous infusion in some of the infants, indicated that the disposition of amikacin was best described by a 2 compartment model. The absorption was evaluated in 8 of the infants after intramuscular injection of 7.5 mg amikacin per kilogram of body weight. The absorption rate, estimated by the tmax, was significantly faster than reported in adults. The total body clearance and apparent volume of distribution were studied in 22 infants after the same dose of amikacin intramuscularly. The body clearance expressed in relation to body surface or body weight was significantly less than in adults and correlated with the postnatal age. No correlation could be demonstrated between clearance and gestational age or birth weight. The volume of distribution per kilogram was significantly greater than in adults. On the basis of the derived kinetic parameters, a dose schedule is presented. In 5 children there was a reasonable agreement between the measured and predicted serum levels."} {"id": "PMID:1277726", "title": "Pentobarbital elimination in patients with poor renal function.", "content": "Drug oxidation is slowed in experimental uremia in animals but has been reported to be normal or accelerated in uremic patients. Eleven normal subjects and 9 uremic patients were each given 100 mg pantobarbital orally. Several blood samples were drawn over a 36-hr period starting on the morning after the dose. Plasma pentobarbital concentration was measured by GLC. The log concentration values were graphed against time elapsed after dose for each patient, and the plasma T/2 and extrapolated value of concentration at the time of drug administration (Co) were determined. The T/2 values in normals ranged from 18 to 48 hr; mean, 26.5 +/- 9.2 (SD). In uremic patients, T/2 values are 10 to 38 hr, mean, 21.3 +/- 8.7. Four of the uremic patients had T/2 values below 18 hr (which was the lowest in the normals). The apparent volumes of distribution of pentobarbital (aVD = dose divided by Co) were 62 +/- 25 L in the normal subjects and 58 +/- 24 L in the uremic patients. The four uremic patients with the short T/2 values tended to have small apparent volumes of distribution so that the metabolic clearnce rates (aVd X 0.693 divided by half-life) were normal in 3 of them. We conclude that pentobarbital elimination is normal in renal failure. Some uremic patients have short plasma T/2 values for pentobarbital, and these more likely result from low apparent volumes of distribution with normal metabolic clearance rates than from accelerated metabolism of pentobarbital.", "contents": "Pentobarbital elimination in patients with poor renal function. Drug oxidation is slowed in experimental uremia in animals but has been reported to be normal or accelerated in uremic patients. Eleven normal subjects and 9 uremic patients were each given 100 mg pantobarbital orally. Several blood samples were drawn over a 36-hr period starting on the morning after the dose. Plasma pentobarbital concentration was measured by GLC. The log concentration values were graphed against time elapsed after dose for each patient, and the plasma T/2 and extrapolated value of concentration at the time of drug administration (Co) were determined. The T/2 values in normals ranged from 18 to 48 hr; mean, 26.5 +/- 9.2 (SD). In uremic patients, T/2 values are 10 to 38 hr, mean, 21.3 +/- 8.7. Four of the uremic patients had T/2 values below 18 hr (which was the lowest in the normals). The apparent volumes of distribution of pentobarbital (aVD = dose divided by Co) were 62 +/- 25 L in the normal subjects and 58 +/- 24 L in the uremic patients. The four uremic patients with the short T/2 values tended to have small apparent volumes of distribution so that the metabolic clearnce rates (aVd X 0.693 divided by half-life) were normal in 3 of them. We conclude that pentobarbital elimination is normal in renal failure. Some uremic patients have short plasma T/2 values for pentobarbital, and these more likely result from low apparent volumes of distribution with normal metabolic clearance rates than from accelerated metabolism of pentobarbital."} {"id": "PMID:1277727", "title": "Elimination of antipyrine and benzo[a]pyrene metabolism in cultured human lymphocytes.", "content": "A strong correlation was found in a carefully selected homogenous population (n = 57) between antipyrine plasma half-life and the percent induction of aryl hydrocarbon hydroxylase by 3-methylcholanthrene in mitogen-stimulated lymphocytes from the same individual. The correlation coefficient of r = 0.923 indicates that antipyrine and benzo[a]pyrene share one or several common determinants that are responsible for the observed interindividual variation in the oxidation rates of the two compounds. When a heterogenous population (n = 80) was studied, the above correlation was not found (r = 0.425).", "contents": "Elimination of antipyrine and benzo[a]pyrene metabolism in cultured human lymphocytes. A strong correlation was found in a carefully selected homogenous population (n = 57) between antipyrine plasma half-life and the percent induction of aryl hydrocarbon hydroxylase by 3-methylcholanthrene in mitogen-stimulated lymphocytes from the same individual. The correlation coefficient of r = 0.923 indicates that antipyrine and benzo[a]pyrene share one or several common determinants that are responsible for the observed interindividual variation in the oxidation rates of the two compounds. When a heterogenous population (n = 80) was studied, the above correlation was not found (r = 0.425)."} {"id": "PMID:1277728", "title": "The clearance of antipyrine and indocyanine green in normal subjects and in patients with chronic lever disease.", "content": "The pharmacokinetics after oral administration of 1,200 mg antipyrine and intravenous administration of 0.5 mg/kg indocyanine green have been investigated in 6 normal subjects and in 20 patients with chronic liver disease of varying etiology. Severe impairment of liver function associated with a decrease in serum albumin, elevation in serum bilirubin, or prolongation in prothrombin time correlated with a fall in the clearance of both drugs. The clearance of the two drugs correlated well in normal subjects and in patients with chronic liver disease. The presence of a surgical portacaval anastomosis was associated with a lower indocyanine green clearance for comparable clearance of antipyrine. The concept of functioning hepatic parenchymal mass is proposed as a common rate-limiting parameter for the elimination of the two drugs.", "contents": "The clearance of antipyrine and indocyanine green in normal subjects and in patients with chronic lever disease. The pharmacokinetics after oral administration of 1,200 mg antipyrine and intravenous administration of 0.5 mg/kg indocyanine green have been investigated in 6 normal subjects and in 20 patients with chronic liver disease of varying etiology. Severe impairment of liver function associated with a decrease in serum albumin, elevation in serum bilirubin, or prolongation in prothrombin time correlated with a fall in the clearance of both drugs. The clearance of the two drugs correlated well in normal subjects and in patients with chronic liver disease. The presence of a surgical portacaval anastomosis was associated with a lower indocyanine green clearance for comparable clearance of antipyrine. The concept of functioning hepatic parenchymal mass is proposed as a common rate-limiting parameter for the elimination of the two drugs."} {"id": "PMID:1277729", "title": "Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin.", "content": "Five patients received a small oral dose of warfarin during and after recovery from acute viral hepatitis. Mean (+/- SD) clearance, volume of distribution, and half-life of the drug were 6.1 +/- 0.9 ml/hr/kg, 0.09 +/- 0.04 L/kg, and 23 +/- 5 hr, respectively, during the acute period. After apparent recovery, observed values were 6.1 +/- 0.7 ml/hr/kg, 0.21 +/- 0.02 L/kg, and 25 +/- 3 hr. These differences were not significant. Pattern of renal elimination of warfarin metabolites and drug protein binding did not change between the two phases. During the acute period of illness, prothrombin time increased in 2 of the 5 subjects, but remained within normal limits in all participants during the recovery period. This study shows that warfarin disposition may not change as a consequence of mild or moderate hepatic impairment.", "contents": "Influence of acute viral hepatitis on disposition and pharmacologic effect of warfarin. Five patients received a small oral dose of warfarin during and after recovery from acute viral hepatitis. Mean (+/- SD) clearance, volume of distribution, and half-life of the drug were 6.1 +/- 0.9 ml/hr/kg, 0.09 +/- 0.04 L/kg, and 23 +/- 5 hr, respectively, during the acute period. After apparent recovery, observed values were 6.1 +/- 0.7 ml/hr/kg, 0.21 +/- 0.02 L/kg, and 25 +/- 3 hr. These differences were not significant. Pattern of renal elimination of warfarin metabolites and drug protein binding did not change between the two phases. During the acute period of illness, prothrombin time increased in 2 of the 5 subjects, but remained within normal limits in all participants during the recovery period. This study shows that warfarin disposition may not change as a consequence of mild or moderate hepatic impairment."} {"id": "PMID:1277730", "title": "Dicloxacillin and cloxacillin: pharmacokinetics in healthy and hemodialysis subjects.", "content": "Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 gm dicloxacillin or 2 gm cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 gm dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 gm in patients is good (75.9% of the dose).", "contents": "Dicloxacillin and cloxacillin: pharmacokinetics in healthy and hemodialysis subjects. Differences in the elimination, distribution, and absorption of dicloxacillin and cloxacillin were studied in a group of healthy individuals with the use of a 2-compartment model. In patients on chronic intermittent hemodialysis, only dicloxacillin was investigated and the results were compared with data obtained in earlier studies on cloxacillin and flucloxacillin. In healthy volunteers the bioavailability after oral administration of 2 gm dicloxacillin or 2 gm cloxacillin amounted to 48.8% and 36.9% of the dose, respectively, when calculated from the area under the serum concentration-time curve, and to 74.1% and 48.5%, respectively, when calculated from the urinary excretion. Individual variation in bioavailability after oral administration was slightly lower for docloxacillin than for cloxacillin. The higher serum concentrations of dicloxacillin, as compared with cloxacillin, are also attributable to slower (renal) elimination (T 1/2: 42 and 33 min, respectively). Analysis of serum concentrations after intravenous administration of 1 and 2 gm dicloxacillin to healthy subjects revealed concentration-dependent kinetics with respect ot renal elimination. In hemodialysis patients the elimination rate of dicloxacillin (T 1/2: 129 min) corresponds with the extrarenal elimination rate in healthy subjects. The bioavailability after oral administration of 1 gm in patients is good (75.9% of the dose)."} {"id": "PMID:1277731", "title": "Skin reaction. A quantitative system for measurement of radiosensitisation in man.", "content": "Areas of skin have been irradiated using a radio-strontium plaque giving 800 to 1100 rad. Visual ranking of the reactions produced proved to be the best method of measuring the response. Erythema was poorly related to dose but in most cases the amount of pigmentation produced was directly related to it. This system, for use in the testing of radiosensitisers, allows a quantitative estimate of enhancement of response to be made.", "contents": "Skin reaction. A quantitative system for measurement of radiosensitisation in man. Areas of skin have been irradiated using a radio-strontium plaque giving 800 to 1100 rad. Visual ranking of the reactions produced proved to be the best method of measuring the response. Erythema was poorly related to dose but in most cases the amount of pigmentation produced was directly related to it. This system, for use in the testing of radiosensitisers, allows a quantitative estimate of enhancement of response to be made."} {"id": "PMID:1277732", "title": "Clinical testing of the radiosensitiser Ro-07-0582. II. Radiosensitisation of normal and hypoxic skin.", "content": "The effectiveness of the radiosensitiser Ro-07-0582 has been tested in man by observing the skin reaction after irradiation using a radio-strontium source with and without administration of the drug. The skin reaction technique has been extended so that skin was irradiated when at low oxygen tension (hypoxic) as well as when fully oxygenated (oxic). Limbs have been made hypoxic by occlusion of the circulation using a sphygmomanometer cuff. To this has been added the prior use of an Esmarch's bandage to reduce the volume of blood in the skin and the enclosing of the limb in a bag of nitrogen. The Oxygen Enhancement Ratios obtained without the sensitiser in nine studies using this system ranged from 1-64 to 2-46. Using Ro-07-0582 skin reactions after oxic exposures were not enhanced but those after hypoxic exposures were markedly increased. The Relative Sensitising Efficiency expresses, as a percentage, the restoration of the sensitivity of cells protected by hypoxia. In six cases where Ro-07-0582 was given in doses ranging from 81 to 165 mg/kg, efficiencies ranged from 27 to 71%. These results can be compared with three studies using metronidazole where efficiencies ranged from 11 to 15%. Using comparable dosage Ro-07-0582 seems approximately three times more effective than metronidazole. In this first study in man, Ro-07-0582 appears to be a highly effective radiosensitiser of hypoxic cells.", "contents": "Clinical testing of the radiosensitiser Ro-07-0582. II. Radiosensitisation of normal and hypoxic skin. The effectiveness of the radiosensitiser Ro-07-0582 has been tested in man by observing the skin reaction after irradiation using a radio-strontium source with and without administration of the drug. The skin reaction technique has been extended so that skin was irradiated when at low oxygen tension (hypoxic) as well as when fully oxygenated (oxic). Limbs have been made hypoxic by occlusion of the circulation using a sphygmomanometer cuff. To this has been added the prior use of an Esmarch's bandage to reduce the volume of blood in the skin and the enclosing of the limb in a bag of nitrogen. The Oxygen Enhancement Ratios obtained without the sensitiser in nine studies using this system ranged from 1-64 to 2-46. Using Ro-07-0582 skin reactions after oxic exposures were not enhanced but those after hypoxic exposures were markedly increased. The Relative Sensitising Efficiency expresses, as a percentage, the restoration of the sensitivity of cells protected by hypoxia. In six cases where Ro-07-0582 was given in doses ranging from 81 to 165 mg/kg, efficiencies ranged from 27 to 71%. These results can be compared with three studies using metronidazole where efficiencies ranged from 11 to 15%. Using comparable dosage Ro-07-0582 seems approximately three times more effective than metronidazole. In this first study in man, Ro-07-0582 appears to be a highly effective radiosensitiser of hypoxic cells."} {"id": "PMID:1277733", "title": "The effect of immobilisation on localisation error in the radiotherapy of head and neck cancer.", "content": "With the use of treatment verification films for the detection of localisation error (LE), a study was undertaken to determine the effect of change in position and immobilisation on LE in the radiotherapy of patients with head and neck cancer. For those patients not immobilised and treated in the lateral position, 28 errors were recorded in a review of 172 films, giving an error incidence of 16%. For patients immobilised by bite block and treated in the supine position, a total of four errors were recorded on review of 382 films, giving an error incidence of 1%. The reduction of LE from 16% to 1% by supine positioning and bite block immobilisation was significant with a P value of less than 0.001. The potential significance of LE in relation to CNS injury and tumour recurrence is discussed.", "contents": "The effect of immobilisation on localisation error in the radiotherapy of head and neck cancer. With the use of treatment verification films for the detection of localisation error (LE), a study was undertaken to determine the effect of change in position and immobilisation on LE in the radiotherapy of patients with head and neck cancer. For those patients not immobilised and treated in the lateral position, 28 errors were recorded in a review of 172 films, giving an error incidence of 16%. For patients immobilised by bite block and treated in the supine position, a total of four errors were recorded on review of 382 films, giving an error incidence of 1%. The reduction of LE from 16% to 1% by supine positioning and bite block immobilisation was significant with a P value of less than 0.001. The potential significance of LE in relation to CNS injury and tumour recurrence is discussed."} {"id": "PMID:1277734", "title": "Keloid scars: a new method of treatment combining surgery with interstitial radiotherapy.", "content": "A method is described for the treatment of the linear keloid scar, by surgical excision and post-operative irradiation delivered locally to the base of the sutured edges of the scar, by an iridium-192 wire. The wire is after-loaded into a plastic tube using the technique described by Paine (1972). A dose of 2000 rad is delivered at a point 2-5 mm from the axis of the wire, opposite its mid-point. Thirty cases have been treated by this method with a follow-up period of two years or longer; five recurrences were found at six months, and a further one by two years. No complications were observed. It is suggested that this represents a rather lower recurrence rate than has been achieved by other methods, and that the dose to the tissue surrounding the scar is less than that which would be the case with conventional superficial radiotherapy - an important consideration in the treatment of young patients, with benign conditions, by irradiation.", "contents": "Keloid scars: a new method of treatment combining surgery with interstitial radiotherapy. A method is described for the treatment of the linear keloid scar, by surgical excision and post-operative irradiation delivered locally to the base of the sutured edges of the scar, by an iridium-192 wire. The wire is after-loaded into a plastic tube using the technique described by Paine (1972). A dose of 2000 rad is delivered at a point 2-5 mm from the axis of the wire, opposite its mid-point. Thirty cases have been treated by this method with a follow-up period of two years or longer; five recurrences were found at six months, and a further one by two years. No complications were observed. It is suggested that this represents a rather lower recurrence rate than has been achieved by other methods, and that the dose to the tissue surrounding the scar is less than that which would be the case with conventional superficial radiotherapy - an important consideration in the treatment of young patients, with benign conditions, by irradiation."} {"id": "PMID:1277735", "title": "On long-term survivals in non-Hodgkin's lymphoma with 'gentle' treatment.", "content": "Eighty-seven cases of non-Hodgkin's lymphomas from the Southern California Permanente Medical Group have been reviewed. The patients were treated between 1953 and 1960, all in an era of 'minimal' radiotherapeutic and chemotherapeutic treatment. The favourable prognostic factors for long-term survival using gentle treatment are, firstly, nodular pattern, presenting in clinically localised Stages I and II and, secondly, diffuse well-differentiated lymphocytic lymphoma (DLWD) presenting either in a localised or generalised fashion. In this series moderate dose irradiation (2500 rad) to involved areas with or without modest chemotherapy has resulted in the survival of 26 out of 32 DLWD patients for more than five years and in most cases for over ten years.", "contents": "On long-term survivals in non-Hodgkin's lymphoma with 'gentle' treatment. Eighty-seven cases of non-Hodgkin's lymphomas from the Southern California Permanente Medical Group have been reviewed. The patients were treated between 1953 and 1960, all in an era of 'minimal' radiotherapeutic and chemotherapeutic treatment. The favourable prognostic factors for long-term survival using gentle treatment are, firstly, nodular pattern, presenting in clinically localised Stages I and II and, secondly, diffuse well-differentiated lymphocytic lymphoma (DLWD) presenting either in a localised or generalised fashion. In this series moderate dose irradiation (2500 rad) to involved areas with or without modest chemotherapy has resulted in the survival of 26 out of 32 DLWD patients for more than five years and in most cases for over ten years."} {"id": "PMID:1277736", "title": "Scleroderma and carcinoma of the lung.", "content": "Two cases of scleroderma and carcinoma of the lung are reported. The 16 previously reported cases in the English literature are reviewed and tabulated in an attempt to determine the pathological and clinical presentation of carcinoma of the lung superimposed on the sclerodermal lung. When patients with scleroderma develop a change in pulmonary symptoms, a superimposed cancer of the lung should be suspected. The relationship between interstitial pulmonary inflammatory disease and cancer of the lung is discussed.", "contents": "Scleroderma and carcinoma of the lung. Two cases of scleroderma and carcinoma of the lung are reported. The 16 previously reported cases in the English literature are reviewed and tabulated in an attempt to determine the pathological and clinical presentation of carcinoma of the lung superimposed on the sclerodermal lung. When patients with scleroderma develop a change in pulmonary symptoms, a superimposed cancer of the lung should be suspected. The relationship between interstitial pulmonary inflammatory disease and cancer of the lung is discussed."} {"id": "PMID:1277737", "title": "Destroyed lung. A report of cases in West Indians and Australian Aborigines.", "content": "A series of patients with total destruction of one lung by bronchiectasis and a normal contralateral lung is reported. Eight cases were West Indians of Negro race and four were Australian Aborigines. The bronchiectasis appears to be of post-infective type and is related to the poor social conditions under which the affected people live. It has also been noted in other developing countries or in under-privileged races in developed countries.", "contents": "Destroyed lung. A report of cases in West Indians and Australian Aborigines. A series of patients with total destruction of one lung by bronchiectasis and a normal contralateral lung is reported. Eight cases were West Indians of Negro race and four were Australian Aborigines. The bronchiectasis appears to be of post-infective type and is related to the poor social conditions under which the affected people live. It has also been noted in other developing countries or in under-privileged races in developed countries."} {"id": "PMID:1277738", "title": "131I Rose Bengal scanning and clearance ratios in the investigation of jaundiced patients.", "content": "It may be difficult to distinguish between obstructive and non-obstructive jaundice despite the use of clinical, biochemical and radiographic tests. Endoscopic cannulation tests promise to be the most accurate means of separating the two groups, but they are not yet widely available, and are not entirely safe. In contrast, the 131I-Rose Bengal test is simple, safe and comparatively widely available. Its accuracy in 70 jaundiced patients is reviewed to determine whether it still has a place in the investigation of jaundiced patients. Blood clearance traces, intestinal radioactivity traces and serial abdominal scans were done during a period of 3 h. The blood clearance ratios were not helpful discriminators, and the most helpful information was the timing of intestinal radioactivity. Its rapid appearance excluded mechanical obstruction. A delay of up to 3 h in its appearance was characteristic of cholestasis. A delay of more than 3 h was found in all cases of mechanical obstruction, but also in ten cases of severe cholestasis which could not be distinguished from those with mechanical obstruction. A follow-up examination within another ten days was of diagnostic value in two of these cases and the overall accuracy of the test was 86%. The potential value of prolonging the test to 24 h is discussed. It is concluded that the 131I-Rose Bengal test is a helpful diagnostic discriminator in the great majority of patients with jaundice. It is offered as a screening procedure for specialised techniques.", "contents": "131I Rose Bengal scanning and clearance ratios in the investigation of jaundiced patients. It may be difficult to distinguish between obstructive and non-obstructive jaundice despite the use of clinical, biochemical and radiographic tests. Endoscopic cannulation tests promise to be the most accurate means of separating the two groups, but they are not yet widely available, and are not entirely safe. In contrast, the 131I-Rose Bengal test is simple, safe and comparatively widely available. Its accuracy in 70 jaundiced patients is reviewed to determine whether it still has a place in the investigation of jaundiced patients. Blood clearance traces, intestinal radioactivity traces and serial abdominal scans were done during a period of 3 h. The blood clearance ratios were not helpful discriminators, and the most helpful information was the timing of intestinal radioactivity. Its rapid appearance excluded mechanical obstruction. A delay of up to 3 h in its appearance was characteristic of cholestasis. A delay of more than 3 h was found in all cases of mechanical obstruction, but also in ten cases of severe cholestasis which could not be distinguished from those with mechanical obstruction. A follow-up examination within another ten days was of diagnostic value in two of these cases and the overall accuracy of the test was 86%. The potential value of prolonging the test to 24 h is discussed. It is concluded that the 131I-Rose Bengal test is a helpful diagnostic discriminator in the great majority of patients with jaundice. It is offered as a screening procedure for specialised techniques."} {"id": "PMID:1277739", "title": "Thermography and radiology complimentary methods for the study of inflammatory diseases.", "content": "The authors have correlated the findings of thermography and radiology in some inflammatory lesions. The two investigations are complementary. Thermography demonstrates changes of vascularity in the acute phase of a lesion whereas radiology is of value in showing structural changes.", "contents": "Thermography and radiology complimentary methods for the study of inflammatory diseases. The authors have correlated the findings of thermography and radiology in some inflammatory lesions. The two investigations are complementary. Thermography demonstrates changes of vascularity in the acute phase of a lesion whereas radiology is of value in showing structural changes."} {"id": "PMID:1277740", "title": "Single bolus versus drip infusion for intravenous cholangiography.", "content": "Biliary tract visualisation in 50 patients examined by infusion of methylglucamine iodipamide was compared, by double-blind technique, to cholangiograms obtained in 50 other patients by a single bolus injection. The infusion technique did not give better results than the single bolus method. In another group of 20 patients, each individual was examined by both methods. The radiographs, read in a double-blind manner, showed both methods to be comparable in demonstrating the biliary system. It seems that other means have to be designed and employed in order to improve the radiographic delineation of the biliary tract.", "contents": "Single bolus versus drip infusion for intravenous cholangiography. Biliary tract visualisation in 50 patients examined by infusion of methylglucamine iodipamide was compared, by double-blind technique, to cholangiograms obtained in 50 other patients by a single bolus injection. The infusion technique did not give better results than the single bolus method. In another group of 20 patients, each individual was examined by both methods. The radiographs, read in a double-blind manner, showed both methods to be comparable in demonstrating the biliary system. It seems that other means have to be designed and employed in order to improve the radiographic delineation of the biliary tract."} {"id": "PMID:1277741", "title": "Gas contrast studies of the biliary tract following reconstructive surgery.", "content": "Forty-seven patients who had previously undergone reconstructive surgery were examined on 70 occasions by gas contrast cholangiography after drinking carbonified water in order to outline the biliary tract. In the light of subsequent clinical and operative findings the radiological appearances are analysed and the value of the technique assessed. There was a close correlation between failure to visualise the biliary tract and obstruction of the anastomosis (85% accurate).", "contents": "Gas contrast studies of the biliary tract following reconstructive surgery. Forty-seven patients who had previously undergone reconstructive surgery were examined on 70 occasions by gas contrast cholangiography after drinking carbonified water in order to outline the biliary tract. In the light of subsequent clinical and operative findings the radiological appearances are analysed and the value of the technique assessed. There was a close correlation between failure to visualise the biliary tract and obstruction of the anastomosis (85% accurate)."} {"id": "PMID:1277742", "title": "The microvasculature of the spleen.", "content": "A method for examining the microvasculature of the dog spleen by angiography is described and the findings are related to morphological studies. The marginal sinus of the lymphoid follicle has been shown to be an important part of the vascular pathway in the spleen. It allows intimate mixing of blood elements and spleen cells and it is suggested that this plays an important immunological role. The control of blood flow to the lymphoid follicle is discussed but requires further elucidation.", "contents": "The microvasculature of the spleen. A method for examining the microvasculature of the dog spleen by angiography is described and the findings are related to morphological studies. The marginal sinus of the lymphoid follicle has been shown to be an important part of the vascular pathway in the spleen. It allows intimate mixing of blood elements and spleen cells and it is suggested that this plays an important immunological role. The control of blood flow to the lymphoid follicle is discussed but requires further elucidation."} {"id": "PMID:1277743", "title": "Angiographic anatomy of the right heart.", "content": "Casts of human hearts were prepared and photographed to illustrate the anatomy of the right heart chambers and ventricular septum. The casts were used to illustrate the anatomy of certain common pathological abnormalities of the ventricular septum and the appearances compared to angiocardiograms.", "contents": "Angiographic anatomy of the right heart. Casts of human hearts were prepared and photographed to illustrate the anatomy of the right heart chambers and ventricular septum. The casts were used to illustrate the anatomy of certain common pathological abnormalities of the ventricular septum and the appearances compared to angiocardiograms."} {"id": "PMID:1277744", "title": "The effect of repeated phlebotomy on bilirubin turnover, bilirubin clearance and unconjugated hyperbilirubinaemia in the Crigler-Najjar syndrome and the jaundiced Gunn rat: application of computers to experimental design.", "content": "1. A multicompartmental model of erythrokinetics and bilirubin production has been developed to predict the consequences of chronic phlebotomy on daily bilirubin turnover. 2. Control values for four physiological variables including bilirubin turnover were determined in a 20-year-old woman with type I congenital nonhaemolytic jaundice (Crigler-Najjar syndrome). With these base-line data, the model predicted the following changes during phlebotomy: a 34% fall in bilirubin turnover; a 240% increase in the haemoglobin content of bone-marrow erythroid precursors; a 25% fall in the half-life of 51Cr-labelled erythrocytes; a characteristic alteration of the erythrocyte survival curve after labelling with [2-14C]glycine. 3. On the assumption, previously validated in normal volunteer subjects and patients with Gilbert's syndrome, that hepatic bilirubin clearance was independent of turnover and would therefore remain unchanged, a fall in plasma unconjugated bilirubin concentration during phlebotomy from 436 to 282 mumol/1 was expected. 4. Accordingly, the patient underwent phlebotomy 350 ml/week for 2 months, and 500 ml/week during an additional 3 months. Appropriate studies during phlebotomy confirmed each of the predictions in paragraph 2 above. In particular, turnover fell by 31%. Unexpectedly, plasma unconjugated bilirubin remained essentially unchanged. Analogous results were observed in phlebotomized jaundiced Gunn rats. 5. Kinetic studies in both the patient and the rats demonstrated that the failure of plasma unconjugated bilirubin to fall in parallel with bilirubin turnover resulted from a prolongation of the terminal half-life of radioactively labelled bilirubin and a fall in bilirubin clearance in every instance. 6. These studies indicate that (a) in congenital non-haemolytic jaundice, bilirubin clearance is uniquely influenced by bilirubin turnover and (b) compartmental modelling and kinetic studies are useful for predicting and interpreting the results of both physiological experiments and experimental therapeutic regimens.", "contents": "The effect of repeated phlebotomy on bilirubin turnover, bilirubin clearance and unconjugated hyperbilirubinaemia in the Crigler-Najjar syndrome and the jaundiced Gunn rat: application of computers to experimental design. 1. A multicompartmental model of erythrokinetics and bilirubin production has been developed to predict the consequences of chronic phlebotomy on daily bilirubin turnover. 2. Control values for four physiological variables including bilirubin turnover were determined in a 20-year-old woman with type I congenital nonhaemolytic jaundice (Crigler-Najjar syndrome). With these base-line data, the model predicted the following changes during phlebotomy: a 34% fall in bilirubin turnover; a 240% increase in the haemoglobin content of bone-marrow erythroid precursors; a 25% fall in the half-life of 51Cr-labelled erythrocytes; a characteristic alteration of the erythrocyte survival curve after labelling with [2-14C]glycine. 3. On the assumption, previously validated in normal volunteer subjects and patients with Gilbert's syndrome, that hepatic bilirubin clearance was independent of turnover and would therefore remain unchanged, a fall in plasma unconjugated bilirubin concentration during phlebotomy from 436 to 282 mumol/1 was expected. 4. Accordingly, the patient underwent phlebotomy 350 ml/week for 2 months, and 500 ml/week during an additional 3 months. Appropriate studies during phlebotomy confirmed each of the predictions in paragraph 2 above. In particular, turnover fell by 31%. Unexpectedly, plasma unconjugated bilirubin remained essentially unchanged. Analogous results were observed in phlebotomized jaundiced Gunn rats. 5. Kinetic studies in both the patient and the rats demonstrated that the failure of plasma unconjugated bilirubin to fall in parallel with bilirubin turnover resulted from a prolongation of the terminal half-life of radioactively labelled bilirubin and a fall in bilirubin clearance in every instance. 6. These studies indicate that (a) in congenital non-haemolytic jaundice, bilirubin clearance is uniquely influenced by bilirubin turnover and (b) compartmental modelling and kinetic studies are useful for predicting and interpreting the results of both physiological experiments and experimental therapeutic regimens."} {"id": "PMID:1277745", "title": "The relation between functioning parietal cell and gastrin cell masses in two groups of duodenal ulcer patients.", "content": "1. Serum gastrin concentrations before and after a standardized meal were determined in twenty-eight patients with duodenal ulcer and in ten normal control subjects. 2. In response to pentagastrin, thirteen of the duodenal ulcer subjects secreted acid within the limits of normal and fifteen secreted in excess. 3. The differences in the basal serum gastrin concentrations between the three groups, normal subjects, acid \"normosecretors\" and hypersecretors were not statistically significant but that of the hypersecretors was suggestively low. 4. The integrated gastrin response and peak gastrin responses to meals were higher in duodenal ulcer patients with normal acid secretion than in the hyper-secretors but the values for the latter were not different from normal subjects. 5. Stabilization of intragastric pH by infusion into the antrum of sodium bicarbonate during the test meal response period did not alter these differences between the two ulcer patient groups. 6. A significant inverse correlation exists between the maximal acid output and the integrated gastrin response in both normal subjects and hypersecreting duodenal ulcer patients. 7. The evidence (a) supports the existence of an inverse relationship between the functioning parietal cell and gastrin cell masses, (b) shows the gastrin response in normosecreting ulcer subjects to be inappropriately high, and (c) suggests that excessive vagotonia exerts trophic effects upon both parietal cell mass and gastrin cell mass.", "contents": "The relation between functioning parietal cell and gastrin cell masses in two groups of duodenal ulcer patients. 1. Serum gastrin concentrations before and after a standardized meal were determined in twenty-eight patients with duodenal ulcer and in ten normal control subjects. 2. In response to pentagastrin, thirteen of the duodenal ulcer subjects secreted acid within the limits of normal and fifteen secreted in excess. 3. The differences in the basal serum gastrin concentrations between the three groups, normal subjects, acid \"normosecretors\" and hypersecretors were not statistically significant but that of the hypersecretors was suggestively low. 4. The integrated gastrin response and peak gastrin responses to meals were higher in duodenal ulcer patients with normal acid secretion than in the hyper-secretors but the values for the latter were not different from normal subjects. 5. Stabilization of intragastric pH by infusion into the antrum of sodium bicarbonate during the test meal response period did not alter these differences between the two ulcer patient groups. 6. A significant inverse correlation exists between the maximal acid output and the integrated gastrin response in both normal subjects and hypersecreting duodenal ulcer patients. 7. The evidence (a) supports the existence of an inverse relationship between the functioning parietal cell and gastrin cell masses, (b) shows the gastrin response in normosecreting ulcer subjects to be inappropriately high, and (c) suggests that excessive vagotonia exerts trophic effects upon both parietal cell mass and gastrin cell mass."} {"id": "PMID:1277746", "title": "Disappearance of 125I-labelled and unlabelled insulins from blood in normal and injured rats.", "content": "1. The disappearance from blood of either 125I-labelled bovine insulin or unlabelled rat insulin after a single intravenous injection has been studied in rats. 2. The disappearance of the labelled insulin was slower than that of native insulin. 3. Ether anaesthesia produced a significant impairment, and bilateral nephrectomy a very marked impairment, of disappearance of the labelled insulin, suggesting that changes in the removal of this tracer may nevertheless parallel changes in the metabolism of native insulin. 4. Simultaneous intravenous injection of unlabelled bovine insulin (1 unit/kg) did not affect disappearance of the labelled insulin. 5. A 20% full-thickness scald injury, produced 2 h previously, had no significant effect on disappearance of the labelled insulin, either with or without the simultaneous administration of unlabelled bovine insulin. 6. The disappearance of unlabelled rat insulin from plasma was also similar in control and scalded rats. 7. It was concluded that the half-life of plasma insulin in the rat, as estimated by either of the techniques used, is not significantly affected by this severe non-haemorrhagic injury.", "contents": "Disappearance of 125I-labelled and unlabelled insulins from blood in normal and injured rats. 1. The disappearance from blood of either 125I-labelled bovine insulin or unlabelled rat insulin after a single intravenous injection has been studied in rats. 2. The disappearance of the labelled insulin was slower than that of native insulin. 3. Ether anaesthesia produced a significant impairment, and bilateral nephrectomy a very marked impairment, of disappearance of the labelled insulin, suggesting that changes in the removal of this tracer may nevertheless parallel changes in the metabolism of native insulin. 4. Simultaneous intravenous injection of unlabelled bovine insulin (1 unit/kg) did not affect disappearance of the labelled insulin. 5. A 20% full-thickness scald injury, produced 2 h previously, had no significant effect on disappearance of the labelled insulin, either with or without the simultaneous administration of unlabelled bovine insulin. 6. The disappearance of unlabelled rat insulin from plasma was also similar in control and scalded rats. 7. It was concluded that the half-life of plasma insulin in the rat, as estimated by either of the techniques used, is not significantly affected by this severe non-haemorrhagic injury."} {"id": "PMID:1277747", "title": "Turnover of plasma glucose and free fatty acids in patients on the first day after myocardial infarction.", "content": "1. The turnover of plasma glucose and free fatty acids was measured in ten patients within 24 h of the onset of symptoms of acute myocardial infarction and in two with symptoms of acute myocardial ischaemia. The measurements were repeated in seven of the patients 12-40 weeks after the acute episode. 2. Both for the patients with acute myocardial infarction alone and for all the individuals studied the turnover of glucose increased with plasma glucose concentration but was not related to the turnover of free fatty acids or the plasma concentrations of free fatty acids, insulin or total catecholamines. There was no obvious difference in the nature of the glucose turnover-concentration relationship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination. 3. For all the individuals studied the turnover of free fatty acids increased with the concentration of these but was not related to the turnover of glucose or the plasma concentrations of glucose, insulin or total catecholamines. There was no obvious difference in the nature of the free fatty acids turnover-concentration relaionship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination.", "contents": "Turnover of plasma glucose and free fatty acids in patients on the first day after myocardial infarction. 1. The turnover of plasma glucose and free fatty acids was measured in ten patients within 24 h of the onset of symptoms of acute myocardial infarction and in two with symptoms of acute myocardial ischaemia. The measurements were repeated in seven of the patients 12-40 weeks after the acute episode. 2. Both for the patients with acute myocardial infarction alone and for all the individuals studied the turnover of glucose increased with plasma glucose concentration but was not related to the turnover of free fatty acids or the plasma concentrations of free fatty acids, insulin or total catecholamines. There was no obvious difference in the nature of the glucose turnover-concentration relationship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination. 3. For all the individuals studied the turnover of free fatty acids increased with the concentration of these but was not related to the turnover of glucose or the plasma concentrations of glucose, insulin or total catecholamines. There was no obvious difference in the nature of the free fatty acids turnover-concentration relaionship between the patients with acute myocardial infarction, with acute myocardial ischaemia and on re-examination."} {"id": "PMID:1277748", "title": "Renal haemodynamics and plasma renin in patients with essential hypertension.", "content": "1. Blood pressure, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in twenty-three patients with essential hypertension and in twenty-one control subjects. Plasma renin concentration was measured in all the hypertensive patients and in fifteen control subjects. 2. GFR and RPF were similar in the hypertensive group and in the control group, whereas the renal vascular resistance was significantly higher in the hypertensive patients. GFR and RPF decreased with increasing blood pressure in both groups. Increasing age induced a further reduction in GFR and RPF in the control subjects but not in the hypertensive patients. 3. Plasma renin concentration in the hypertensive group did not differ from that in the control subjects. The concentration was not correlated to age in either the hypertensive or normal group. 4. Plasma renin index was positively correlated to GFR and RPF and inversely correlated to filtration fraction and renal vascular resistance. 5. It is concluded that GFR and RPF depend on blood pressure in both hypertensive patients and normotensive control subjects. In contrast to the control group, the age effect was negligible in the hypertensive group. It is suggested that renin release depends on changes in renal vascular resistance in the arterioles at the glomerulus and the results support the baroreceptor theory of renin release.", "contents": "Renal haemodynamics and plasma renin in patients with essential hypertension. 1. Blood pressure, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured in twenty-three patients with essential hypertension and in twenty-one control subjects. Plasma renin concentration was measured in all the hypertensive patients and in fifteen control subjects. 2. GFR and RPF were similar in the hypertensive group and in the control group, whereas the renal vascular resistance was significantly higher in the hypertensive patients. GFR and RPF decreased with increasing blood pressure in both groups. Increasing age induced a further reduction in GFR and RPF in the control subjects but not in the hypertensive patients. 3. Plasma renin concentration in the hypertensive group did not differ from that in the control subjects. The concentration was not correlated to age in either the hypertensive or normal group. 4. Plasma renin index was positively correlated to GFR and RPF and inversely correlated to filtration fraction and renal vascular resistance. 5. It is concluded that GFR and RPF depend on blood pressure in both hypertensive patients and normotensive control subjects. In contrast to the control group, the age effect was negligible in the hypertensive group. It is suggested that renin release depends on changes in renal vascular resistance in the arterioles at the glomerulus and the results support the baroreceptor theory of renin release."} {"id": "PMID:1277749", "title": "Effect of vasopressin on plasma volume and renin release in man.", "content": "1. Arginine vasopressin was infused into seven healthy young male volunteers at 12-5 and 25 units/min for 1 h at each dose. Plasma renin activity fell sharply and progressively in each subject. The mean fall was 47% and 66% of the initial value at the end of the lower and higher rates of arginine vasopressin infusion respectively; over 70% of the observed fall in plasma renin activity occurred at the end of the first infusion period. 2. The majority of the plasma arginine vasopressin concentrations achieved were within the physiological range observed after fluid deprivation and orthostatic stress in man, particularly at the lower rate of infusion. 3. There was no change of arterial pressure, despite a slight bradycardia at the lower rate of infusion; at the higher rate of infusion, there was only a very slight pressor response. 4. There was a concomitant and significant fall of plasma protein concentration and peripheral venous packed cell volume without any significant change of plasma sodium concentration or plasma osmolality, implying an expansion of plasma volume. 5. The results indicate that, in man, physiologically relevant amounts of arginine vasopressin suppress the rate of renin secretion indirectly by increasing the plasma volume at the expense of the extravascular fluid volume.", "contents": "Effect of vasopressin on plasma volume and renin release in man. 1. Arginine vasopressin was infused into seven healthy young male volunteers at 12-5 and 25 units/min for 1 h at each dose. Plasma renin activity fell sharply and progressively in each subject. The mean fall was 47% and 66% of the initial value at the end of the lower and higher rates of arginine vasopressin infusion respectively; over 70% of the observed fall in plasma renin activity occurred at the end of the first infusion period. 2. The majority of the plasma arginine vasopressin concentrations achieved were within the physiological range observed after fluid deprivation and orthostatic stress in man, particularly at the lower rate of infusion. 3. There was no change of arterial pressure, despite a slight bradycardia at the lower rate of infusion; at the higher rate of infusion, there was only a very slight pressor response. 4. There was a concomitant and significant fall of plasma protein concentration and peripheral venous packed cell volume without any significant change of plasma sodium concentration or plasma osmolality, implying an expansion of plasma volume. 5. The results indicate that, in man, physiologically relevant amounts of arginine vasopressin suppress the rate of renin secretion indirectly by increasing the plasma volume at the expense of the extravascular fluid volume."} {"id": "PMID:1277750", "title": "Biochemical and morphological studies on human jejunal mucosa maintained in culture.", "content": "1. The combination of a wire-mesh support with the roller-tube technique is described as a procedure for the culture of human jejunal mucosa in vitro. 2. The technique has been applied to fragments (approximately 10 mg) of jejunal biopsies from both normal subjects and patients with coeliac disease. 3. The cultured tissue has been shown by radio-autography to incorporate [3H]leucine into proteins of the villus epithelial cells and [3H]thymidine into nucleic acid, predominantly by the enteroblasts. 4. Although the tissue protein DNA contents fall during culture, it was found that the combined tissue and medium DNA content remained constant during culture and may be used as a reference for enzyme and biochemical studies on cultured intestinal biopsies.", "contents": "Biochemical and morphological studies on human jejunal mucosa maintained in culture. 1. The combination of a wire-mesh support with the roller-tube technique is described as a procedure for the culture of human jejunal mucosa in vitro. 2. The technique has been applied to fragments (approximately 10 mg) of jejunal biopsies from both normal subjects and patients with coeliac disease. 3. The cultured tissue has been shown by radio-autography to incorporate [3H]leucine into proteins of the villus epithelial cells and [3H]thymidine into nucleic acid, predominantly by the enteroblasts. 4. Although the tissue protein DNA contents fall during culture, it was found that the combined tissue and medium DNA content remained constant during culture and may be used as a reference for enzyme and biochemical studies on cultured intestinal biopsies."} {"id": "PMID:1277751", "title": "The porphyrinogenic effects of kryptopyrrole in the rat and the occurrence of urinary kryptopyrrole in human hereditary hepatic porphyria.", "content": "1. Kryptopyrrole (2,4-dimethyl-3-ethyl pyrrole) was shown to elevate the urinary porphyrin excretion and the hepatic content of porphyrins in the rat. The simultaneous administration of sigma-aminolaevulinic acid increased these effects. 2. Kryptopyrrole was present in the urine of patients with hereditary hepatic porphyria, in attack and in remission, but not in those with latent porphyria.", "contents": "The porphyrinogenic effects of kryptopyrrole in the rat and the occurrence of urinary kryptopyrrole in human hereditary hepatic porphyria. 1. Kryptopyrrole (2,4-dimethyl-3-ethyl pyrrole) was shown to elevate the urinary porphyrin excretion and the hepatic content of porphyrins in the rat. The simultaneous administration of sigma-aminolaevulinic acid increased these effects. 2. Kryptopyrrole was present in the urine of patients with hereditary hepatic porphyria, in attack and in remission, but not in those with latent porphyria."} {"id": "PMID:1277752", "title": "The renal handling of insulin and thyroid hormones in normal man.", "content": "1. The renal extraction of insulin and thyroid hormones T3 and T4 was studied in man by right renal vein catheterization. 2. The mean renal extraction of insulin was 0-46, suggesting that the right renal vein should be utilized in comparable studies. 3. No renal extraction of thyroid hormones was detected.", "contents": "The renal handling of insulin and thyroid hormones in normal man. 1. The renal extraction of insulin and thyroid hormones T3 and T4 was studied in man by right renal vein catheterization. 2. The mean renal extraction of insulin was 0-46, suggesting that the right renal vein should be utilized in comparable studies. 3. No renal extraction of thyroid hormones was detected."} {"id": "PMID:1277753", "title": "The effect of anaesthesia of the airway in dog and man: a study of respiratory reflexes, sensations and lung mechanics.", "content": "1. The effect of breathing an anaesthetic aerosol of 5% bupivacaine hydrochloride has been assessed in dog and man. 2. In the dog, the cough reflex was abolished and the Hering-Breuer inflation reflex severely impaired or abolished; breathing became slower and deeper; no pathological changes were found in the lungs of these dogs. 3. In man, no untoward effects resulted from a 10 min period of aerosol inhalation; there were no systematic effects on airway resistance or lung volumes and the cough reflex in response to either tactile or chemical (citric acid aerosol) stimulation was invariably abolished. The Hering-Breuer inflation reflex was impaired, but this was not associated with any change in resting ventilation. The Ve/CO2 response was enhanced after aerosol anaesthesia; subjects felt an exaggerated dyspnoea. The aerosol anaesthesia abolished the afferent pathway of a reflexly elicited bronchoconstriction in one subject. There was no effect on the ability to hold the breath, or on the quality of the associated sensation. 4. Control aerosols of sodium chloride solution or phosphate buffer produced no effects. Control experiments with intravenous infusions of bupivacaine proved that none of the effects could have been produced by systemic effects of the absorbed anaesthetic. 5. Plasma concentrations of bupivacaine in man did not exceed a recognized toxic level. The experiments demonstrate a safe reversible anaesthesia of the airways in man lasting for a period of 10-20 min.", "contents": "The effect of anaesthesia of the airway in dog and man: a study of respiratory reflexes, sensations and lung mechanics. 1. The effect of breathing an anaesthetic aerosol of 5% bupivacaine hydrochloride has been assessed in dog and man. 2. In the dog, the cough reflex was abolished and the Hering-Breuer inflation reflex severely impaired or abolished; breathing became slower and deeper; no pathological changes were found in the lungs of these dogs. 3. In man, no untoward effects resulted from a 10 min period of aerosol inhalation; there were no systematic effects on airway resistance or lung volumes and the cough reflex in response to either tactile or chemical (citric acid aerosol) stimulation was invariably abolished. The Hering-Breuer inflation reflex was impaired, but this was not associated with any change in resting ventilation. The Ve/CO2 response was enhanced after aerosol anaesthesia; subjects felt an exaggerated dyspnoea. The aerosol anaesthesia abolished the afferent pathway of a reflexly elicited bronchoconstriction in one subject. There was no effect on the ability to hold the breath, or on the quality of the associated sensation. 4. Control aerosols of sodium chloride solution or phosphate buffer produced no effects. Control experiments with intravenous infusions of bupivacaine proved that none of the effects could have been produced by systemic effects of the absorbed anaesthetic. 5. Plasma concentrations of bupivacaine in man did not exceed a recognized toxic level. The experiments demonstrate a safe reversible anaesthesia of the airways in man lasting for a period of 10-20 min."} {"id": "PMID:1277754", "title": "The relation between potassium in body fluids and total body potassium in healthy and diabetic subjects.", "content": "1. The concentration of potassium in the erythrocytes and the plasma of forty-one normal subjects and twenty-five diabetic patients was measured and the results were used to calculate the total amount of potassium in the erythrocyte mass and the total amount of potassium in the plasma. The total body potassium was measured in a whole-body monitor. 2. In normal subjects a close correlation was found between total erythrocyte potassium and total body potassium and also between total plasma potassium and total body potassium. 3. The regression relation between total body potassium and total erythrocyte potassium in normal subjects was used to predict the total body potassium in diabetic patients. There was reasonable agreement between the measured and predicted total body potassium but there was poor agreement between the measured total body potassium and that predicted from the patient's height and age or height and age or height, weight and age.", "contents": "The relation between potassium in body fluids and total body potassium in healthy and diabetic subjects. 1. The concentration of potassium in the erythrocytes and the plasma of forty-one normal subjects and twenty-five diabetic patients was measured and the results were used to calculate the total amount of potassium in the erythrocyte mass and the total amount of potassium in the plasma. The total body potassium was measured in a whole-body monitor. 2. In normal subjects a close correlation was found between total erythrocyte potassium and total body potassium and also between total plasma potassium and total body potassium. 3. The regression relation between total body potassium and total erythrocyte potassium in normal subjects was used to predict the total body potassium in diabetic patients. There was reasonable agreement between the measured and predicted total body potassium but there was poor agreement between the measured total body potassium and that predicted from the patient's height and age or height and age or height, weight and age."} {"id": "PMID:1277755", "title": "The encephalopathic action of five-carbon-atom fatty acids in the rabbit.", "content": "1. Five-carbon-atom organic acids (C-5 acids) have been administered intravenously to rabbits with ventriculocisternal perfusion and continuous electroencephalographic recording (EEG). The concentration of the acids in the cerebrospinal fluid (CSF) perfusate have been compared with changes in integrated low-frequency activity in the EEG. 2. The C-5 acids investigated were those accumulating in inborn errors of metabolism, i.e. isovaleric acid, beta-methylcrotonic acid, tiglic acid and alpha-keto- and alpha-hydroxy-isovaleric acid. There activity was compared with that of valeric acid. 3. Valeric acid and isovaleric acid produced coma and pronounced increase in slow-wave electrical activity and these changes paralleled the increase in concentration of the acids in the CSF perfusate. 4. The concentration of beta-methylcrotonic acid and tiglic acid in the CSF perfusate reached values comparable with valeric acid and isovaleric acid but showed less encephalopathic activity. An interaction between beta-methylcrotonic acid and isovaleric acid was observed. 5. Although the concentrations of alpha-ketoisovaleric acid and alpha-hydroxyisovaleric acid rose to the lesser extent in the CSF perfusate, changes in rousability of the animal and in the EEG recording were demonstrated. 6. It is concluded that all the C-5 acids tested have encephalopathic activity although this is lessened by the presence of either a double bond or an oxygenated functional group.", "contents": "The encephalopathic action of five-carbon-atom fatty acids in the rabbit. 1. Five-carbon-atom organic acids (C-5 acids) have been administered intravenously to rabbits with ventriculocisternal perfusion and continuous electroencephalographic recording (EEG). The concentration of the acids in the cerebrospinal fluid (CSF) perfusate have been compared with changes in integrated low-frequency activity in the EEG. 2. The C-5 acids investigated were those accumulating in inborn errors of metabolism, i.e. isovaleric acid, beta-methylcrotonic acid, tiglic acid and alpha-keto- and alpha-hydroxy-isovaleric acid. There activity was compared with that of valeric acid. 3. Valeric acid and isovaleric acid produced coma and pronounced increase in slow-wave electrical activity and these changes paralleled the increase in concentration of the acids in the CSF perfusate. 4. The concentration of beta-methylcrotonic acid and tiglic acid in the CSF perfusate reached values comparable with valeric acid and isovaleric acid but showed less encephalopathic activity. An interaction between beta-methylcrotonic acid and isovaleric acid was observed. 5. Although the concentrations of alpha-ketoisovaleric acid and alpha-hydroxyisovaleric acid rose to the lesser extent in the CSF perfusate, changes in rousability of the animal and in the EEG recording were demonstrated. 6. It is concluded that all the C-5 acids tested have encephalopathic activity although this is lessened by the presence of either a double bond or an oxygenated functional group."} {"id": "PMID:1277756", "title": "Effect of inhibition of gluconeogenesis on ammonia production in the perfused rat kidney.", "content": "1. Gluconeogenesis from lactate or from glutamine is inhibited by 90-100% by sodium quinolinate (1 mmol/l) or 3-mercaptopicolinate (150 nmol/l) in the perfused rat kidney. L-Tryptophan is not metabolized and is without effect. 2. Lactate uptake and glucose production are inhibited to the same degree by 3-mercaptopicolinate in the kidneys of well-fed or starved rats. 3. Inhibition of gluconeogenesis from glutamine (1 mmol/l) by 3-mercaptopicolinate is accompanied by 50% inhibition of ammonia production, and 34% inhibition of glutamine uptake, in the kidneys of acidotic rats. Ammonia production from glutamine was not inhibited in kidneys from non-acidotic rats. 4. It is concluded that the increased rate of gluconeogenesis from glutamine which occurs in acidotic rats is an essential and primary event regulating all of the increase in ammonia formation.", "contents": "Effect of inhibition of gluconeogenesis on ammonia production in the perfused rat kidney. 1. Gluconeogenesis from lactate or from glutamine is inhibited by 90-100% by sodium quinolinate (1 mmol/l) or 3-mercaptopicolinate (150 nmol/l) in the perfused rat kidney. L-Tryptophan is not metabolized and is without effect. 2. Lactate uptake and glucose production are inhibited to the same degree by 3-mercaptopicolinate in the kidneys of well-fed or starved rats. 3. Inhibition of gluconeogenesis from glutamine (1 mmol/l) by 3-mercaptopicolinate is accompanied by 50% inhibition of ammonia production, and 34% inhibition of glutamine uptake, in the kidneys of acidotic rats. Ammonia production from glutamine was not inhibited in kidneys from non-acidotic rats. 4. It is concluded that the increased rate of gluconeogenesis from glutamine which occurs in acidotic rats is an essential and primary event regulating all of the increase in ammonia formation."} {"id": "PMID:1277757", "title": "Absorption of galactose by the rat small intestine in vivo: proximal-distal kinetic gradients and a new method to express absorption per enterocyte.", "content": "1. The absorption in vivo of D-galactose by the rat small intestine has been examined in proximal jejunum and distal ileum by use of a recirculation-perfusion technique. 2. Multiple sequential perfusions over 4 h produced no subsequent functional or morphological damage in the perfused segments. 3. Absorption of galactose from 8 and 64 mmol/l solutions was found to be independent of flow rate over the range 1-0-6-5 ml/min. 4. Galactose absorption in both the jejunum and the ileum exhibited saturation kinetics of the Michaelis-Menten type, and phlorrhizin sensitivity. Sorbose was only absorbed minimally. These observations demonstrate that galactose is absorbed by carrier-mediated transport and that there is no significant passive diffusive component in vivo. 5. Under the stated experimental conditions, the maximum absorptive capacity was 4-5 times greater in the jejunum than in the ileum. The Michaelis constant for galactose was higher in the jejunum than in the ileum. 6. Enterocytes were isolated from perfused segments and quantified by DNA assay with a correction for yield. In this manner, the absorptive capacity per enterocyte was calculated. 7. The maximum absorptive capacity per enterocyte was 3-5 times greater in the jejunum than in the ileum.", "contents": "Absorption of galactose by the rat small intestine in vivo: proximal-distal kinetic gradients and a new method to express absorption per enterocyte. 1. The absorption in vivo of D-galactose by the rat small intestine has been examined in proximal jejunum and distal ileum by use of a recirculation-perfusion technique. 2. Multiple sequential perfusions over 4 h produced no subsequent functional or morphological damage in the perfused segments. 3. Absorption of galactose from 8 and 64 mmol/l solutions was found to be independent of flow rate over the range 1-0-6-5 ml/min. 4. Galactose absorption in both the jejunum and the ileum exhibited saturation kinetics of the Michaelis-Menten type, and phlorrhizin sensitivity. Sorbose was only absorbed minimally. These observations demonstrate that galactose is absorbed by carrier-mediated transport and that there is no significant passive diffusive component in vivo. 5. Under the stated experimental conditions, the maximum absorptive capacity was 4-5 times greater in the jejunum than in the ileum. The Michaelis constant for galactose was higher in the jejunum than in the ileum. 6. Enterocytes were isolated from perfused segments and quantified by DNA assay with a correction for yield. In this manner, the absorptive capacity per enterocyte was calculated. 7. The maximum absorptive capacity per enterocyte was 3-5 times greater in the jejunum than in the ileum."} {"id": "PMID:1277758", "title": "Studies of amino acid and protein metabolism in normal man with L-[U-14C]tyrosine.", "content": "1. Six men were infused intravenously for 10 h with a tracer amount of L-[U-14C]tyrosine while on a standardized food intake. 2. Measurements of plasma L-[14C]-tyrosine specific radioactivity and the excretion rate of 14CO2 were made at frequent intervals and showed plateau labelling of plasma and expired carbon dioxide within 6-8 h. The tyrosine flux was calculated from the specific radioactivity in plasma at plateau value. 3. The excretion rate of 14CO2, corrected for retention of label within the bicarbonate pool, showed that oxidation accounted for 20% of the tyrosine flux. Urinary excretion of label was negligible. 4. Rates of protein synthesis were calculated from the flux of tyrosine after subtracting the proportion oxidized. Although the mean rate of synthesis was consistent with other measurements of protein turnover, the individual values ranged from 284 to 387 g/day. The variation was not reduced by relating turnover to body weight, lean body mass or energy expenditure. 5. Estimating the rates of protein breakdown from the tyrosine flux involved some assumptions about pathways of phenylalanine metabolism. The use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover.", "contents": "Studies of amino acid and protein metabolism in normal man with L-[U-14C]tyrosine. 1. Six men were infused intravenously for 10 h with a tracer amount of L-[U-14C]tyrosine while on a standardized food intake. 2. Measurements of plasma L-[14C]-tyrosine specific radioactivity and the excretion rate of 14CO2 were made at frequent intervals and showed plateau labelling of plasma and expired carbon dioxide within 6-8 h. The tyrosine flux was calculated from the specific radioactivity in plasma at plateau value. 3. The excretion rate of 14CO2, corrected for retention of label within the bicarbonate pool, showed that oxidation accounted for 20% of the tyrosine flux. Urinary excretion of label was negligible. 4. Rates of protein synthesis were calculated from the flux of tyrosine after subtracting the proportion oxidized. Although the mean rate of synthesis was consistent with other measurements of protein turnover, the individual values ranged from 284 to 387 g/day. The variation was not reduced by relating turnover to body weight, lean body mass or energy expenditure. 5. Estimating the rates of protein breakdown from the tyrosine flux involved some assumptions about pathways of phenylalanine metabolism. The use of a labelled essential amino acid would therefore give more accurate values for short-term measurements of whole body protein turnover."} {"id": "PMID:1277759", "title": "Haemodynamic studies in dogs with chronic bile-duct ligation.", "content": "1. Dogs with bile-duct ligation retain salt and water and form ascites. The present study was under-taken to examine the role of haemodynamic factors in the aetiology of this sodium retention. 2. Haemodynamic studies were performed in five dogs before and 5 weeks after bile-duct ligation. 3. After the operation there was an insignificant fall in mean arterial pressure, a significant rise in mean cardiac index and significant fall in mean total peripheral resistance. 4. It is concluded that heart failure is not a factor in renal sodium retention of the dog with bile-duct ligation, since the central venous pressure was not elevated. 5. The haemodynamic pattern and the tendency to salt retention in the dog with chronic bile-duct ligation closely resemble findings reported in patients with cirrhosis of the liver, and it is suggested that oedema formation in patients with cirrhosis of the liver and dogs with chronic bile-duct ligation shares a common aetiology.", "contents": "Haemodynamic studies in dogs with chronic bile-duct ligation. 1. Dogs with bile-duct ligation retain salt and water and form ascites. The present study was under-taken to examine the role of haemodynamic factors in the aetiology of this sodium retention. 2. Haemodynamic studies were performed in five dogs before and 5 weeks after bile-duct ligation. 3. After the operation there was an insignificant fall in mean arterial pressure, a significant rise in mean cardiac index and significant fall in mean total peripheral resistance. 4. It is concluded that heart failure is not a factor in renal sodium retention of the dog with bile-duct ligation, since the central venous pressure was not elevated. 5. The haemodynamic pattern and the tendency to salt retention in the dog with chronic bile-duct ligation closely resemble findings reported in patients with cirrhosis of the liver, and it is suggested that oedema formation in patients with cirrhosis of the liver and dogs with chronic bile-duct ligation shares a common aetiology."} {"id": "PMID:1277760", "title": "The effect of active immunization against aldosterone on the colonic potential response and sodium excretion in rabbits.", "content": "1. A group of rabbits was actively immunized against aldosterone and their subsequent response to infused aldosterone and to dietary sodium restriction was compared with that of a control group. 2. Colonic electrical potential difference (CP) was used as an index of relative mineralocorticoid activity in both groups of animals. 3. Infusion of aldosterone produced a rise in CP to a maximum of -50 to -70 mV at rates of infusion of 55-270 pmol min-1 kg-1. In contrast, the immune group showed no change until infusion dose rates of 2700 pmol min-1 kg-1 were used. 4. During dietary sodium restriction, CP increased in normal rabbits to a significantly greater degree than in immune animals although cumulative urinary sodium losses were the same in both groups. 5. The ability of the immune animals to remain in sodium balance despite physiological aldosterone blockade suggests that aldosterone is not an essential component of their sodium-conservation mechanisms.", "contents": "The effect of active immunization against aldosterone on the colonic potential response and sodium excretion in rabbits. 1. A group of rabbits was actively immunized against aldosterone and their subsequent response to infused aldosterone and to dietary sodium restriction was compared with that of a control group. 2. Colonic electrical potential difference (CP) was used as an index of relative mineralocorticoid activity in both groups of animals. 3. Infusion of aldosterone produced a rise in CP to a maximum of -50 to -70 mV at rates of infusion of 55-270 pmol min-1 kg-1. In contrast, the immune group showed no change until infusion dose rates of 2700 pmol min-1 kg-1 were used. 4. During dietary sodium restriction, CP increased in normal rabbits to a significantly greater degree than in immune animals although cumulative urinary sodium losses were the same in both groups. 5. The ability of the immune animals to remain in sodium balance despite physiological aldosterone blockade suggests that aldosterone is not an essential component of their sodium-conservation mechanisms."} {"id": "PMID:1277768", "title": "\"Bicarbonate resistant\" metabolic acidosis in association with ethylene glycol intoxication.", "content": "A case of massive ingestion of ethylene glycol is described. The clinical characteristics of this disorder such as persistent metabolic acidosis and oxaluria as well as changes in serum osmolality that may accompany ingestion of certain toxins are emphasized. The rapid clearance of ethylene glycol from the blood during hemodialysis is noted and the use of ethyl alcohol to block metabolic conversion of ethylene glycol to oxalic acid, which is also a toxin, is described. The importance of early diagnosis and therapy is stressed.", "contents": "\"Bicarbonate resistant\" metabolic acidosis in association with ethylene glycol intoxication. A case of massive ingestion of ethylene glycol is described. The clinical characteristics of this disorder such as persistent metabolic acidosis and oxaluria as well as changes in serum osmolality that may accompany ingestion of certain toxins are emphasized. The rapid clearance of ethylene glycol from the blood during hemodialysis is noted and the use of ethyl alcohol to block metabolic conversion of ethylene glycol to oxalic acid, which is also a toxin, is described. The importance of early diagnosis and therapy is stressed."} {"id": "PMID:1277769", "title": "Salicylate poisoning complicated by fluid retention.", "content": "We have presented two cases of salicylate poisoning that demonstrate fluid retention in the face of adequate hydration, resembling the syndrome of inappropriate secretion of ADH. These cases necessitated marked alterations from normal fluid therapy. Mannitol was found to be an effective, albeit transient, diuretic for treating the acute symptoms associated with fluid retention, but only strict fluid restriction resulted in a prompt and satisfactory diuresis.", "contents": "Salicylate poisoning complicated by fluid retention. We have presented two cases of salicylate poisoning that demonstrate fluid retention in the face of adequate hydration, resembling the syndrome of inappropriate secretion of ADH. These cases necessitated marked alterations from normal fluid therapy. Mannitol was found to be an effective, albeit transient, diuretic for treating the acute symptoms associated with fluid retention, but only strict fluid restriction resulted in a prompt and satisfactory diuresis."} {"id": "PMID:1277770", "title": "1,1,1-trichloroethane: report of a fatal intoxication.", "content": "TCE was indicated in the accidental death of a woman cleaning up a paint spill in an enclosed, poorly ventilated room. Blood and tissue concentrations of TCE were measured by head-space gas chromatography. The concentrations found were compared with previously reported concentrations concluding that the demonstrable presence of TCE in blood at a concentration above 1.0 to 1.5 mg/100 ml would be consistent with death. However, the rapid dissipation of TCE from blood dictates that its presence in post mortem samples at any concentration must be considered as a factor in determining the cause of death.", "contents": "1,1,1-trichloroethane: report of a fatal intoxication. TCE was indicated in the accidental death of a woman cleaning up a paint spill in an enclosed, poorly ventilated room. Blood and tissue concentrations of TCE were measured by head-space gas chromatography. The concentrations found were compared with previously reported concentrations concluding that the demonstrable presence of TCE in blood at a concentration above 1.0 to 1.5 mg/100 ml would be consistent with death. However, the rapid dissipation of TCE from blood dictates that its presence in post mortem samples at any concentration must be considered as a factor in determining the cause of death."} {"id": "PMID:1277771", "title": "Cadmium, lead, and copper blood levels in normal children.", "content": "Cadmium, lead, and copper levels were measured in duplicate whole blood samples from 60 apparently normal children, ranging in age from 2 months to 13 years, who were hospitalized for elective surgery. Metals were measured by atomic absorption spectroscopy after the samples were chemically oxidized and digested. Cadmium was concentrated by dithizone extraction before analysis. Blood cadmium averaged 0.66 mug/100 gm, with a standard deviation of 0.25. No samples had cadmium concentrations less than could be detectable. The average concentration of lead was 15.7 mug/100 gm with a standard deviation of 6.33. Copper averaged 123 mug/100 gm with a standard deviation of 35.5. Tolerance intervals were calculated for each metal in order to estimate the bounds of whole blood metal values in normal children. The intervals containing 95% of normal values with a probability of .95 were 0.22-1.70 mug Cd/100 gm, 0.87-30.5 mug Pb/100 gm, and 40.0-206 mug Cu/100 gm.", "contents": "Cadmium, lead, and copper blood levels in normal children. Cadmium, lead, and copper levels were measured in duplicate whole blood samples from 60 apparently normal children, ranging in age from 2 months to 13 years, who were hospitalized for elective surgery. Metals were measured by atomic absorption spectroscopy after the samples were chemically oxidized and digested. Cadmium was concentrated by dithizone extraction before analysis. Blood cadmium averaged 0.66 mug/100 gm, with a standard deviation of 0.25. No samples had cadmium concentrations less than could be detectable. The average concentration of lead was 15.7 mug/100 gm with a standard deviation of 6.33. Copper averaged 123 mug/100 gm with a standard deviation of 35.5. Tolerance intervals were calculated for each metal in order to estimate the bounds of whole blood metal values in normal children. The intervals containing 95% of normal values with a probability of .95 were 0.22-1.70 mug Cd/100 gm, 0.87-30.5 mug Pb/100 gm, and 40.0-206 mug Cu/100 gm."} {"id": "PMID:1277772", "title": "Influence of \"thickening\" agents on the antidotal efficacy of activated charcoal.", "content": "The addition of \"thickening\" agents such as bentonite and carboxymethylcellulose to activated charcoal slurries considerably improves the palatability of this antidote yet does not reduce the efficacy of the activated charcoal in reducing the gastrointestinal absorption of aspirin. Flavoring of such preparations may further enhance this palatability.", "contents": "Influence of \"thickening\" agents on the antidotal efficacy of activated charcoal. The addition of \"thickening\" agents such as bentonite and carboxymethylcellulose to activated charcoal slurries considerably improves the palatability of this antidote yet does not reduce the efficacy of the activated charcoal in reducing the gastrointestinal absorption of aspirin. Flavoring of such preparations may further enhance this palatability."} {"id": "PMID:1277776", "title": "Community absorption of the mentally ill: the new challenge.", "content": "In 1975, twelve years after enactment of the Community Mental Health Centers Act, we find one of the greatest obstacles to fulfillment of our hopes to be pervasive hostility to acceptance of the mentally ill in many communities. The River Region Program has hurdled this obstacle by breaking the artificially large mental health catchment areas into manageable segments of 16 smaller service areas close to the people it serves in seven counties of Kentucky. In each of these service areas it has involved a broad spectrum of citizens in the planning of every service. All of this is of particular relevance today in light of the supreme Court's Donaldson decision, that mentally ill persons cannot be confined involuntarily if they are not dangerous and can live safely in the outside world. The \"outside world\" must be prepared to receive these people, and we in the mental health field must do our job in this vital preparation.", "contents": "Community absorption of the mentally ill: the new challenge. In 1975, twelve years after enactment of the Community Mental Health Centers Act, we find one of the greatest obstacles to fulfillment of our hopes to be pervasive hostility to acceptance of the mentally ill in many communities. The River Region Program has hurdled this obstacle by breaking the artificially large mental health catchment areas into manageable segments of 16 smaller service areas close to the people it serves in seven counties of Kentucky. In each of these service areas it has involved a broad spectrum of citizens in the planning of every service. All of this is of particular relevance today in light of the supreme Court's Donaldson decision, that mentally ill persons cannot be confined involuntarily if they are not dangerous and can live safely in the outside world. The \"outside world\" must be prepared to receive these people, and we in the mental health field must do our job in this vital preparation."} {"id": "PMID:1277777", "title": "Crisis intervention: effects of crisis intervention on family survivors of sudden death situations.", "content": "A controlled study that examined the effects of a short-term crisis service given to a group of families recently bereaved through a sudden death within the family is reported. The results reveal that sudden death does have a major impact on recently bereaved families in terms of increased risk of ill health, poor coping behavior, and disturbed social functioning when compared to nonbereaved families. However, the short-term crisis service appeared to have no major impact upon postbereavement adjustment. Discussion centered around possible reasons for failure of the short-term crisis services.", "contents": "Crisis intervention: effects of crisis intervention on family survivors of sudden death situations. A controlled study that examined the effects of a short-term crisis service given to a group of families recently bereaved through a sudden death within the family is reported. The results reveal that sudden death does have a major impact on recently bereaved families in terms of increased risk of ill health, poor coping behavior, and disturbed social functioning when compared to nonbereaved families. However, the short-term crisis service appeared to have no major impact upon postbereavement adjustment. Discussion centered around possible reasons for failure of the short-term crisis services."} {"id": "PMID:1277778", "title": "A mental health interaction program in a community college.", "content": "This paper presents an interaction program between a community college and two community mental health resources in the college's geographical area as viewed from the vantage point of the college. As described in a complementary paper written by the same authors viewing the interaction from the vantage point of one of the mental health agencies, the primary aim in these interactions is to provide improved mental health services through cooperative training of college counselors and psychiatric residents. In addition, from the college's view a secondary aim has been the freeing of counselors for more functions of an educational and outreach nature.", "contents": "A mental health interaction program in a community college. This paper presents an interaction program between a community college and two community mental health resources in the college's geographical area as viewed from the vantage point of the college. As described in a complementary paper written by the same authors viewing the interaction from the vantage point of one of the mental health agencies, the primary aim in these interactions is to provide improved mental health services through cooperative training of college counselors and psychiatric residents. In addition, from the college's view a secondary aim has been the freeing of counselors for more functions of an educational and outreach nature."} {"id": "PMID:1277779", "title": "A study of paraprofessionals in mental health.", "content": "This article summarizes data gathered on 15 paraprofessional training programs sponsored by the National Institute of Mental Health (NIMH). Data on the backgrounds of trainees working as paraprofessionals are presented along with a breakdown of the kinds of tasks in which they are employed, as well as characteristics linked with ratings of success and retention in the programs. Trainees tended to be employed in a wide variety of tasks, often at rather sophisticated levels. Analysis of the tasks indicates that projects are fulfilling the NIMH New Careers goal of contributing to greater community impact in mental health. Results corroborate earlier findings that para professionals have been accepted both by professionals and clients.", "contents": "A study of paraprofessionals in mental health. This article summarizes data gathered on 15 paraprofessional training programs sponsored by the National Institute of Mental Health (NIMH). Data on the backgrounds of trainees working as paraprofessionals are presented along with a breakdown of the kinds of tasks in which they are employed, as well as characteristics linked with ratings of success and retention in the programs. Trainees tended to be employed in a wide variety of tasks, often at rather sophisticated levels. Analysis of the tasks indicates that projects are fulfilling the NIMH New Careers goal of contributing to greater community impact in mental health. Results corroborate earlier findings that para professionals have been accepted both by professionals and clients."} {"id": "PMID:1277780", "title": "The Alabama \"right to treatment\" case: an opportunity not to be missed.", "content": "Recent pessimistic criticism of right to treatment decisions is unwarranted. The developing law contains a great deal of flexibility, and this can be creatively utilized to secure resources for community-based services. Courts' emphasis on the physical framework of care is an intentional effort to avoid interfering with program decisions and thus represents a reaffirmation of confidence that professionals can, if provided adequate resources, be relied on to make program decisions. Time should not be spent decrying the effect of an undesirable development of right to treatment law, but rather in formulating and stimulating development of the law in a manner consistent with current trends in the delivery of services.", "contents": "The Alabama \"right to treatment\" case: an opportunity not to be missed. Recent pessimistic criticism of right to treatment decisions is unwarranted. The developing law contains a great deal of flexibility, and this can be creatively utilized to secure resources for community-based services. Courts' emphasis on the physical framework of care is an intentional effort to avoid interfering with program decisions and thus represents a reaffirmation of confidence that professionals can, if provided adequate resources, be relied on to make program decisions. Time should not be spent decrying the effect of an undesirable development of right to treatment law, but rather in formulating and stimulating development of the law in a manner consistent with current trends in the delivery of services."} {"id": "PMID:1277781", "title": "Two studies of comparative stigma: employer attitudes and practices toward rehabilitated convicts, mental and tuberculosis patients.", "content": "Two studies compared the effects of stigmatization on two questionnaire measures of social distance and on offers of employment in retail sales. Employers' questionnaire responses revealed less social distance only with tuberculosis patients, compared to exconvicts, exmental patients or marginally adjusted individuals, all of whom did not differ among themselves. There were no differences in the number or conditions of retail sales job offers obtained by six competent experimenters role playing each of three stigmatizing conditions. The results of the studies are seen as reducing concern over the recent changes in California mental health laws which make involuntary commitment in mental hospitals more difficult and may increase the number of convicts who would otherwise become mental patients. Satisfactory employment, often related to low prisoner and mental patient recidivism rates, may be equally accessible to competent exmental patients and felons.", "contents": "Two studies of comparative stigma: employer attitudes and practices toward rehabilitated convicts, mental and tuberculosis patients. Two studies compared the effects of stigmatization on two questionnaire measures of social distance and on offers of employment in retail sales. Employers' questionnaire responses revealed less social distance only with tuberculosis patients, compared to exconvicts, exmental patients or marginally adjusted individuals, all of whom did not differ among themselves. There were no differences in the number or conditions of retail sales job offers obtained by six competent experimenters role playing each of three stigmatizing conditions. The results of the studies are seen as reducing concern over the recent changes in California mental health laws which make involuntary commitment in mental hospitals more difficult and may increase the number of convicts who would otherwise become mental patients. Satisfactory employment, often related to low prisoner and mental patient recidivism rates, may be equally accessible to competent exmental patients and felons."} {"id": "PMID:1277782", "title": "A profile of the rural community mental health center.", "content": "This paper-part of a national study of community mental health worker role activism-compares community mental health center with their counterparts in other geographic areas. Rural workers were most likely to view their centers as being most like social agencies. Their endorsement of community mental health ideology was also significantly higher. Role was measured from two perspectives: organizational and personal. Again, staff at rural community mental health centers were significantly different: They endorsed the highest levels of both organizational and personal activism and showed the least discrepancy between the two. It is concluded that rural community mental health centers and their staff represent an important and unique response to the problem of community mental health services delivery.", "contents": "A profile of the rural community mental health center. This paper-part of a national study of community mental health worker role activism-compares community mental health center with their counterparts in other geographic areas. Rural workers were most likely to view their centers as being most like social agencies. Their endorsement of community mental health ideology was also significantly higher. Role was measured from two perspectives: organizational and personal. Again, staff at rural community mental health centers were significantly different: They endorsed the highest levels of both organizational and personal activism and showed the least discrepancy between the two. It is concluded that rural community mental health centers and their staff represent an important and unique response to the problem of community mental health services delivery."} {"id": "PMID:1277783", "title": "Teaching nuns' perceptions of white and black pupils as a function of authoritarianism and other factors.", "content": "A sample of 283 teching nuns described the White Pupil, the Black Pupil, and the Ideal Pupil on an adjective description form. A Prejudice score was computed by subtracting the Ideal minus Black differences summed across 52 items from the Ideal minus White differences. Analyses based on 269 subjects revealed that neither age nor amount of prior contact with minorities predicted level of prejiduce. However, high and low-F-scale scorers differed significantly on the Prejudice score and on selected pupil perception factors. Implications in regard to training programs on racial attitudes were discussed.", "contents": "Teaching nuns' perceptions of white and black pupils as a function of authoritarianism and other factors. A sample of 283 teching nuns described the White Pupil, the Black Pupil, and the Ideal Pupil on an adjective description form. A Prejudice score was computed by subtracting the Ideal minus Black differences summed across 52 items from the Ideal minus White differences. Analyses based on 269 subjects revealed that neither age nor amount of prior contact with minorities predicted level of prejiduce. However, high and low-F-scale scorers differed significantly on the Prejudice score and on selected pupil perception factors. Implications in regard to training programs on racial attitudes were discussed."} {"id": "PMID:1277784", "title": "Effectiveness of college students in an incentive community program for chronic hospitalized patients.", "content": "The study describes and assesses an incentive community program implemented by college students for all of the chronic hospitalized patients living in a locked ward. Behavioral ratings of ward behavior and discharge rates were significantly higher for the experimental than for matched control patients. Bed-wetting was eliminated in 70% of the bed-wetting patients. Students rated the incentive community program more effective in changing the behavior of patients than students' ratings of a case-aide program. No differences in patient behaviors were found between the incentive community and case-aide program.", "contents": "Effectiveness of college students in an incentive community program for chronic hospitalized patients. The study describes and assesses an incentive community program implemented by college students for all of the chronic hospitalized patients living in a locked ward. Behavioral ratings of ward behavior and discharge rates were significantly higher for the experimental than for matched control patients. Bed-wetting was eliminated in 70% of the bed-wetting patients. Students rated the incentive community program more effective in changing the behavior of patients than students' ratings of a case-aide program. No differences in patient behaviors were found between the incentive community and case-aide program."} {"id": "PMID:1277785", "title": "Evaluation of televised anticipatory guidance to primiparae.", "content": "In a controlled study, programs offering televised anticipatory guidance to primiparae during the immediate postpartum period were shown to have a beneficial effect on a mother's perceptions of her infant as measured by the Neonatal Perception Inventory (NPI). Among mothers viewing the programs, a significant increase occurred (P less than .01) in the number having a positive perception of their infants at age 1 month. Since the Neonatal Perception Inventory has proved a reliable indicator of a child's emotional well-being at age 4 1/2, televised guidance is recommended as an effective, economical measure with a potential for reducing the incidence of emotional disorder in children.", "contents": "Evaluation of televised anticipatory guidance to primiparae. In a controlled study, programs offering televised anticipatory guidance to primiparae during the immediate postpartum period were shown to have a beneficial effect on a mother's perceptions of her infant as measured by the Neonatal Perception Inventory (NPI). Among mothers viewing the programs, a significant increase occurred (P less than .01) in the number having a positive perception of their infants at age 1 month. Since the Neonatal Perception Inventory has proved a reliable indicator of a child's emotional well-being at age 4 1/2, televised guidance is recommended as an effective, economical measure with a potential for reducing the incidence of emotional disorder in children."} {"id": "PMID:1277786", "title": "Community mental health ideology scale: social work norms.", "content": "The present study reports mean scores obtained by two groups of professionals deeply involved in the community mental health movement on the Community Mental Health Ideology Scale. Professional social workers and social work graduate students were not included in the scale makers original criterion group. The high mean scores obtained by these groups led the authors to the conclusion that social workers show the potential for a strong role in the \"third phase\" of mental health care and delivery.", "contents": "Community mental health ideology scale: social work norms. The present study reports mean scores obtained by two groups of professionals deeply involved in the community mental health movement on the Community Mental Health Ideology Scale. Professional social workers and social work graduate students were not included in the scale makers original criterion group. The high mean scores obtained by these groups led the authors to the conclusion that social workers show the potential for a strong role in the \"third phase\" of mental health care and delivery."} {"id": "PMID:1277787", "title": "An evaluative paradigm for community mental health centers using an automated data system.", "content": "A methodology is presented for the evaluation of community mental health centers using data routinely collected by an automated patient management system (Multistate Information System). Four community mental health centers whose catchment areas were widely diverse in composition participated in the study. A generalized evaluation paradigm was developed with measures and objectives formulated to analyze various stages of care as patients progressed through the community mental health center system. The stages covered were admission, initial modality of service, service delivery in terms of types and amounts of services rendered and termination. Each other was analyzed independently of the others and it was ascertained that the methodology produced useful and informative evaluative data across all four centers.", "contents": "An evaluative paradigm for community mental health centers using an automated data system. A methodology is presented for the evaluation of community mental health centers using data routinely collected by an automated patient management system (Multistate Information System). Four community mental health centers whose catchment areas were widely diverse in composition participated in the study. A generalized evaluation paradigm was developed with measures and objectives formulated to analyze various stages of care as patients progressed through the community mental health center system. The stages covered were admission, initial modality of service, service delivery in terms of types and amounts of services rendered and termination. Each other was analyzed independently of the others and it was ascertained that the methodology produced useful and informative evaluative data across all four centers."} {"id": "PMID:1277788", "title": "[Use of sulfonylurea preparations in the treatment of children with diabetes mellitus].", "content": "Compensation with normoglycemia and aglycoseurea for periods of from 6 months to 6 years was reached in 53 patients suffering from manifest diabetes mellitus, as a result of application of sulphanilurea preparations. Of this number 34 children were under insulin therapy before the beginning of sulphanilamide treatment. In 8 cases sulphanilurea preparations were cancelled with persistence of stable compensation; in 5 of them there occured normalization of GTT and in 2 GTT became doubtful. A necessity of using insulin occurred later in 21 of 53 patients (in 3 temporarily and in 18 -- constantly) as a result of intercurrent diseases, stress situations or frequent coarse breaks in the diet.", "contents": "[Use of sulfonylurea preparations in the treatment of children with diabetes mellitus]. Compensation with normoglycemia and aglycoseurea for periods of from 6 months to 6 years was reached in 53 patients suffering from manifest diabetes mellitus, as a result of application of sulphanilurea preparations. Of this number 34 children were under insulin therapy before the beginning of sulphanilamide treatment. In 8 cases sulphanilurea preparations were cancelled with persistence of stable compensation; in 5 of them there occured normalization of GTT and in 2 GTT became doubtful. A necessity of using insulin occurred later in 21 of 53 patients (in 3 temporarily and in 18 -- constantly) as a result of intercurrent diseases, stress situations or frequent coarse breaks in the diet."} {"id": "PMID:1277848", "title": "On bleeding and clotting problems in post-traumatic states.", "content": "The most common bleeding and clotting problems in post-traumatic states are reviewed. The normal response of the coagulation system and the fibrinolytic system to trauma is described; this response must be considered when studying the abnormal situations. The laboratory tests need not be numerous or sophisticated but they must be repeated often enough to understand and interpret the data. A proper understanding of these abnormalities forms the rational basis for the correct choice of therapy, and is of utmost importance in the management of post-traumatic patients.", "contents": "On bleeding and clotting problems in post-traumatic states. The most common bleeding and clotting problems in post-traumatic states are reviewed. The normal response of the coagulation system and the fibrinolytic system to trauma is described; this response must be considered when studying the abnormal situations. The laboratory tests need not be numerous or sophisticated but they must be repeated often enough to understand and interpret the data. A proper understanding of these abnormalities forms the rational basis for the correct choice of therapy, and is of utmost importance in the management of post-traumatic patients."} {"id": "PMID:1277850", "title": "Thromboembolic disease: prophylaxis and treatment.", "content": "Thromboembolic disease ranks among the most dangerous and common complication in the postoperative or post-traumatic patient. As previously mentioned, the incidence is increasing and fatalities from this complication have also risen substantially. The pathogenesis of thromboembolic disease and the predictability of its occurrence remain elusive. Based upon evidence suggesting that the thrombotic process may begin during surgery, greater attention should be given to the use of prophylactic agents before as well as during the operative procedure. The search continues for a safe, oral agent uniformly effective in preventing thromboembolism.", "contents": "Thromboembolic disease: prophylaxis and treatment. Thromboembolic disease ranks among the most dangerous and common complication in the postoperative or post-traumatic patient. As previously mentioned, the incidence is increasing and fatalities from this complication have also risen substantially. The pathogenesis of thromboembolic disease and the predictability of its occurrence remain elusive. Based upon evidence suggesting that the thrombotic process may begin during surgery, greater attention should be given to the use of prophylactic agents before as well as during the operative procedure. The search continues for a safe, oral agent uniformly effective in preventing thromboembolism."} {"id": "PMID:1277851", "title": "Blood viscosity changes after trauma. Use of dextran-40 in correction of microcirculatory insufficiency.", "content": "Trauma causes a definite increase in packed cell viscosity and intravascular cellular aggregation. As a result, total body oxygen consumption decreases markedly. When packed cell viscosity is lowered by infusion of dextran-40, total body oxygen consumption progressively increases to normal values. It does not appear unreasonable to conclude that in traumatized patients, restoration of microcirculatory blood flow is of great importance in reestablishing an effective circulating blood volume and that normalization of blood viscosity after trauma may be of considerable benefit.", "contents": "Blood viscosity changes after trauma. Use of dextran-40 in correction of microcirculatory insufficiency. Trauma causes a definite increase in packed cell viscosity and intravascular cellular aggregation. As a result, total body oxygen consumption decreases markedly. When packed cell viscosity is lowered by infusion of dextran-40, total body oxygen consumption progressively increases to normal values. It does not appear unreasonable to conclude that in traumatized patients, restoration of microcirculatory blood flow is of great importance in reestablishing an effective circulating blood volume and that normalization of blood viscosity after trauma may be of considerable benefit."} {"id": "PMID:1277853", "title": "Acute respiratory failure.", "content": "There appears to be a great similarity between all of the various types of Adult Respiratory Distress Syndromes (ARDS) in that they are all characterized by progressively increasing interstitial edema in the lungs and a reduced functional residual capacity. Early diagnosis is mandatory and therapy should be started as soon as there is a reasonable suspicion, based on the patient's injury or illness and the previous condition of his lungs, that acute respiratory failure is developing. Sepsis, shock, CNS or thoracic disease and trauma are important associated factors. Blood gas changes usually cannot be appreciated clinically until the respiratory problem is quite severe. Accordingly, serial blood gas analyses should be performed on any patient who has a reasonable chance of developing ARDS. We have found that changes in the estimated AaDO2 on room air are especially helpful. Any deterioration in the patient's clinical condition, blood gases or ventilatory effort should be considered as an indication for early ventilatory assistance. Control of the primary process, careful dehydration, high tidal volumes, and PEEP are the mainstays of therapy. Serial blood gases and careful observation of the patient's effective compliance are essential to determine the optimal ventilator setting and the optimal amount of PEEP. Recently intermittent mandatory ventilation (IMV) with very large amounts of PEEP have been reported to be of value. Early administration of massive steroids should be considered if the patient fails to respond promptly to correction of the underlying etiologic problem, particularly sepsis, careful progressive dehydration and optimal expansion of the alveoli, with high tidal volumes and PEEP.", "contents": "Acute respiratory failure. There appears to be a great similarity between all of the various types of Adult Respiratory Distress Syndromes (ARDS) in that they are all characterized by progressively increasing interstitial edema in the lungs and a reduced functional residual capacity. Early diagnosis is mandatory and therapy should be started as soon as there is a reasonable suspicion, based on the patient's injury or illness and the previous condition of his lungs, that acute respiratory failure is developing. Sepsis, shock, CNS or thoracic disease and trauma are important associated factors. Blood gas changes usually cannot be appreciated clinically until the respiratory problem is quite severe. Accordingly, serial blood gas analyses should be performed on any patient who has a reasonable chance of developing ARDS. We have found that changes in the estimated AaDO2 on room air are especially helpful. Any deterioration in the patient's clinical condition, blood gases or ventilatory effort should be considered as an indication for early ventilatory assistance. Control of the primary process, careful dehydration, high tidal volumes, and PEEP are the mainstays of therapy. Serial blood gases and careful observation of the patient's effective compliance are essential to determine the optimal ventilator setting and the optimal amount of PEEP. Recently intermittent mandatory ventilation (IMV) with very large amounts of PEEP have been reported to be of value. Early administration of massive steroids should be considered if the patient fails to respond promptly to correction of the underlying etiologic problem, particularly sepsis, careful progressive dehydration and optimal expansion of the alveoli, with high tidal volumes and PEEP."} {"id": "PMID:1277854", "title": "The acutely dypsneic patient.", "content": "The limited variation of pulmonary responses to disease--dyspnea, cough, production of adventitious sounds, sputum production, and hemoptysis--complicates the differential diagnosis of the acutely ill patient with obvious severe pulmonary disease. This paper attempts to reinforce and redefine this problem: acute cardiac and pulmonary dyspnea can generally be separated by quick but careful clinical analysis; mis-diagnosis may lead to disaster since effective treatment of one is frequently harmful to the other.", "contents": "The acutely dypsneic patient. The limited variation of pulmonary responses to disease--dyspnea, cough, production of adventitious sounds, sputum production, and hemoptysis--complicates the differential diagnosis of the acutely ill patient with obvious severe pulmonary disease. This paper attempts to reinforce and redefine this problem: acute cardiac and pulmonary dyspnea can generally be separated by quick but careful clinical analysis; mis-diagnosis may lead to disaster since effective treatment of one is frequently harmful to the other."} {"id": "PMID:1277877", "title": "Hypocalcaemia of acute pancreatitis: the effect of hypoalbuminaemia.", "content": "Hypoalbuminaemia has been consistently observed in a prospective study of 130 patients with acute pancreatitis. A study was initiated, therefore, to find out if the hypocalcaemia of acute pancreatitis could be explained by the associated hypoalbuminaemia. 64.4% of all serum calcium results were in the apparently hypocalcaemic range. A comparable incidence of hypoalbuminaemia was observed. The 'uncorrected' total serum calcium and serum albumin showed a similar pattern in their daily changes and also a significant correlation overall. When correction of serum calcium was made for albumin levels, only 10.9% of all results represented varying degrees of 'true' hypocalcaemia. Mortality and severity of acute pancreatitis related as closely to hypoalbuminaemia as to uncorrected hypocalcaemia. It is concluded that a low serum albumin should be regarded as the most common cause of a low serum calcium in acute pancreatitis. Routine albumin administration is proposed, a procedure which has been shown to be associated with improved mortality rate and morbidity in this disease.", "contents": "Hypocalcaemia of acute pancreatitis: the effect of hypoalbuminaemia. Hypoalbuminaemia has been consistently observed in a prospective study of 130 patients with acute pancreatitis. A study was initiated, therefore, to find out if the hypocalcaemia of acute pancreatitis could be explained by the associated hypoalbuminaemia. 64.4% of all serum calcium results were in the apparently hypocalcaemic range. A comparable incidence of hypoalbuminaemia was observed. The 'uncorrected' total serum calcium and serum albumin showed a similar pattern in their daily changes and also a significant correlation overall. When correction of serum calcium was made for albumin levels, only 10.9% of all results represented varying degrees of 'true' hypocalcaemia. Mortality and severity of acute pancreatitis related as closely to hypoalbuminaemia as to uncorrected hypocalcaemia. It is concluded that a low serum albumin should be regarded as the most common cause of a low serum calcium in acute pancreatitis. Routine albumin administration is proposed, a procedure which has been shown to be associated with improved mortality rate and morbidity in this disease."} {"id": "PMID:1277878", "title": "Patient tolerance of long-term diuretic/potassium supplement therapy.", "content": "Forty patients with congestive heart failure or hypertensive heart disease were given long-term maintenance treatment with a combined bumetanide/slow-release potassium supplement preparation ('Burinex K'). Stabilised doses ranged from 0.5 mg to 2 mg bumetanide with from 7.7 mmol to 30.8 mmol potassium. Patients took doses either at 9 a.m. or at 5 p.m. daily during a series of alternate 2 to 4-weekly treatment periods. Analysis of patient preference for morning or evening diuresis showed that the majority (72.5%), including all 18 patients who went out to work, preferred the evening regimen. Bumetanide proved to be a highly effective diuretic, irrespective of time of administration. Evening diuresis was associated with a statistically significant increase in the 24-hour excretion of sodium. Serial laboratory analyses showed no clinically significant changes in serum potassium or other parameters examined an in contrast to other diuretics bumetanide produced no significant hyperuricaemic effects.", "contents": "Patient tolerance of long-term diuretic/potassium supplement therapy. Forty patients with congestive heart failure or hypertensive heart disease were given long-term maintenance treatment with a combined bumetanide/slow-release potassium supplement preparation ('Burinex K'). Stabilised doses ranged from 0.5 mg to 2 mg bumetanide with from 7.7 mmol to 30.8 mmol potassium. Patients took doses either at 9 a.m. or at 5 p.m. daily during a series of alternate 2 to 4-weekly treatment periods. Analysis of patient preference for morning or evening diuresis showed that the majority (72.5%), including all 18 patients who went out to work, preferred the evening regimen. Bumetanide proved to be a highly effective diuretic, irrespective of time of administration. Evening diuresis was associated with a statistically significant increase in the 24-hour excretion of sodium. Serial laboratory analyses showed no clinically significant changes in serum potassium or other parameters examined an in contrast to other diuretics bumetanide produced no significant hyperuricaemic effects."} {"id": "PMID:1277879", "title": "Treatment of hay fever in general practice by hyposensitization, using 'Pollinex'.", "content": "Twenty-six patients from a general practice suffering with clear-cut seasonal rhinitis due to grass pollen were treated with 3 injections, at 10 to 14 day intervals, of a modified grass pollen allergens tyrosine adsorbate ('Pollinex'), prior to the 1975 pollen season. Of the 26 patients, only 6 had previously had variable forms of hyposensitization. Despite the very high pollen counts in the 1975 pollen season the overall success rate of the hyposensitization was 73% and results were better in the patients who had not been previously hyposensitized. There was only one adverse local reaction to the injection which was not severe enough to discontinue the treatment.", "contents": "Treatment of hay fever in general practice by hyposensitization, using 'Pollinex'. Twenty-six patients from a general practice suffering with clear-cut seasonal rhinitis due to grass pollen were treated with 3 injections, at 10 to 14 day intervals, of a modified grass pollen allergens tyrosine adsorbate ('Pollinex'), prior to the 1975 pollen season. Of the 26 patients, only 6 had previously had variable forms of hyposensitization. Despite the very high pollen counts in the 1975 pollen season the overall success rate of the hyposensitization was 73% and results were better in the patients who had not been previously hyposensitized. There was only one adverse local reaction to the injection which was not severe enough to discontinue the treatment."} {"id": "PMID:1277880", "title": "An ophthalmic study of ibuprofen in rheumatoid conditions.", "content": "A total of 247 patients suffering from rheumatoid arthritis and allied conditions were referred for routine ophthalmological examination with particular reference to ocular rheumatoid involvement. Of these, 197 were already receiving ibuprofen before their first assessment while 50 had a baseline assessment before commencement of ibrupofen therapy. All patients were examined on at least two occasions. No macular lesions were discovered which could be directly attributed to ibuprofen therapy.", "contents": "An ophthalmic study of ibuprofen in rheumatoid conditions. A total of 247 patients suffering from rheumatoid arthritis and allied conditions were referred for routine ophthalmological examination with particular reference to ocular rheumatoid involvement. Of these, 197 were already receiving ibuprofen before their first assessment while 50 had a baseline assessment before commencement of ibrupofen therapy. All patients were examined on at least two occasions. No macular lesions were discovered which could be directly attributed to ibuprofen therapy."} {"id": "PMID:1277881", "title": "Intravenous fusidic acid ('Fucidin') in the management of severe staphylococcal infections: a review of 46 cases.", "content": "Case reports are reviewed of 46 patients with severe, life-threatening infections, mainly staphylococcal, who were treated with intravenous fusidic acid. Overall, 22 (48%) patients survived and 24 died, 10 of these within 24 hours of commencing treatment with fusidic acid. Thirty-nine patients received unsuccessful antibiotic therapy prior to the administration of fusidic acid. It was not possible to relate prior antibiotic treatment to outcome, and, in such severe infections, complicating diseases had an adverse effect upon survival. It is concluded that intravenous fusidic acid ('Fucidin') has an important place in the treatment of severe staphylococcal infections.", "contents": "Intravenous fusidic acid ('Fucidin') in the management of severe staphylococcal infections: a review of 46 cases. Case reports are reviewed of 46 patients with severe, life-threatening infections, mainly staphylococcal, who were treated with intravenous fusidic acid. Overall, 22 (48%) patients survived and 24 died, 10 of these within 24 hours of commencing treatment with fusidic acid. Thirty-nine patients received unsuccessful antibiotic therapy prior to the administration of fusidic acid. It was not possible to relate prior antibiotic treatment to outcome, and, in such severe infections, complicating diseases had an adverse effect upon survival. It is concluded that intravenous fusidic acid ('Fucidin') has an important place in the treatment of severe staphylococcal infections."} {"id": "PMID:1277882", "title": "Cephradine in the treatment of chronic recurrent infections of the urinary tract.", "content": "Twenty-two patients with chronic recurrent bacterial urinary tract infection, most of whom had underlying physical abnormalities of the tract, were treated with 500 mg cephradine 4-times daily for 10 to 15 days. Eight patients remained completely clear of infection after 2 to 3 months of treatment. This was regarded as a satisfactory result in view of the difficulty in treating this type of case and considering previous unsuccessful courses of antibacterial therapy.", "contents": "Cephradine in the treatment of chronic recurrent infections of the urinary tract. Twenty-two patients with chronic recurrent bacterial urinary tract infection, most of whom had underlying physical abnormalities of the tract, were treated with 500 mg cephradine 4-times daily for 10 to 15 days. Eight patients remained completely clear of infection after 2 to 3 months of treatment. This was regarded as a satisfactory result in view of the difficulty in treating this type of case and considering previous unsuccessful courses of antibacterial therapy."} {"id": "PMID:1277887", "title": "Isosorbide dinitrate and intra-aortic balloon pumping in preinfarctional angina. Effects on central circulatory dynamics.", "content": "The dynamics of the central circulation were measured by a radionuclidic technique in 18 men with high-risk preinfarctional angina who received therapy with isosorbide dinitrate (n equals 18), intra-aortic balloon pumping (n equals 8), or both (n equals 8). Administration of 5 mg of isosorbide dinitrate sublinqually was associated with a reduction in stroke volume index (SVI), cardiac index (CI), systemic arterial blood pressure, and left ventricular end-diastolic volume (LVEDV) and with increased left ventricular ejection fraction (LVEF). Intra-aortic balloon pumping did not alter SVI or CI, but decreased systolic blood pressure and LVEDV and increased LVEF and diastolic blood pressure. The combination of therapy with isosorbide dinitrate and intraaortic balloon pumping resulted in decreased SVI, systolic blood pressure, and LVEDV and increased LVEF. Thus, therapy with isosorbide dinitrate reduced left ventricular preload, and intra-aortic balloon pumping reduced blood pressure, which resulted in a decreased LVEDV and an increase in LVEF. Therapy with isosorbide dinitrate and intra-aortic balloon pumping act to alter central circulatory dynamics in favor of reducing myocardial oxygen demand.", "contents": "Isosorbide dinitrate and intra-aortic balloon pumping in preinfarctional angina. Effects on central circulatory dynamics. The dynamics of the central circulation were measured by a radionuclidic technique in 18 men with high-risk preinfarctional angina who received therapy with isosorbide dinitrate (n equals 18), intra-aortic balloon pumping (n equals 8), or both (n equals 8). Administration of 5 mg of isosorbide dinitrate sublinqually was associated with a reduction in stroke volume index (SVI), cardiac index (CI), systemic arterial blood pressure, and left ventricular end-diastolic volume (LVEDV) and with increased left ventricular ejection fraction (LVEF). Intra-aortic balloon pumping did not alter SVI or CI, but decreased systolic blood pressure and LVEDV and increased LVEF and diastolic blood pressure. The combination of therapy with isosorbide dinitrate and intraaortic balloon pumping resulted in decreased SVI, systolic blood pressure, and LVEDV and increased LVEF. Thus, therapy with isosorbide dinitrate reduced left ventricular preload, and intra-aortic balloon pumping reduced blood pressure, which resulted in a decreased LVEDV and an increase in LVEF. Therapy with isosorbide dinitrate and intra-aortic balloon pumping act to alter central circulatory dynamics in favor of reducing myocardial oxygen demand."} {"id": "PMID:1277888", "title": "A trial of aerosolized theophylline in relieving bronchospasm.", "content": "Theophylline was administered as an aerosol to nine patients with known bronchospastic disease. No significant improvement in the forced expiratory volume in one second was observed after administration of aerosolized theophylline, although improvement did occur following administration of aerosolized isoproterenol. The theoretic mechanisms of bronchodilator aerosols are discussed, as well as the possible reasons for not obtaining a response with administration of theophylline.", "contents": "A trial of aerosolized theophylline in relieving bronchospasm. Theophylline was administered as an aerosol to nine patients with known bronchospastic disease. No significant improvement in the forced expiratory volume in one second was observed after administration of aerosolized theophylline, although improvement did occur following administration of aerosolized isoproterenol. The theoretic mechanisms of bronchodilator aerosols are discussed, as well as the possible reasons for not obtaining a response with administration of theophylline."} {"id": "PMID:1277889", "title": "Marked depth of ST-segment depression during treadmill exercise testing; indicator of severe coronary artery disease.", "content": "This study was designed to evaluate whether treadmill stress testing would facilitate selection of patients with advanced coronary artery disease and, specifically, whether markedly abnormal ischemic responses could be used as indicators of severity of disease. Among 59 consecutive patients with documented coronary artery disease having both maximal treadmill testing and coronary angiographic studies, 15 (group 1) had normal responses to exercise, 18 (group 2) showed 1 to 2.9 mm \"ischemic\" (flat or downward-sloping) ST-segment depression, and 26 (group 3) demonstrated marked (or equal to 3 mm) ischemic responses. Group 3 had statistically significant higher incidences of triple-vessel disease (18/26; 69 percent) and proximal lesions of the left anterior descending coronary artery (24/26; 92 percent), compared with group 1 (2/15 and 10/15, respectively) and group 2 (6/18 and 12/18, respectively). Group 3 also manifested more extensive disease than groups 1 and 2 (judged by scoring system of Friesinger et al), with a score of 11 or more in 18 of 26 patients. We conclude that marked depth of \"ischemic\" ST-segment depression aids in identifying that subgroup of the coronary population with severe coronary artery disease and, therefore, serves as a useful means of culling out patients with a potentially serious prognosis who might benefit from intensive diagnostic or therapeutic interventions.", "contents": "Marked depth of ST-segment depression during treadmill exercise testing; indicator of severe coronary artery disease. This study was designed to evaluate whether treadmill stress testing would facilitate selection of patients with advanced coronary artery disease and, specifically, whether markedly abnormal ischemic responses could be used as indicators of severity of disease. Among 59 consecutive patients with documented coronary artery disease having both maximal treadmill testing and coronary angiographic studies, 15 (group 1) had normal responses to exercise, 18 (group 2) showed 1 to 2.9 mm \"ischemic\" (flat or downward-sloping) ST-segment depression, and 26 (group 3) demonstrated marked (or equal to 3 mm) ischemic responses. Group 3 had statistically significant higher incidences of triple-vessel disease (18/26; 69 percent) and proximal lesions of the left anterior descending coronary artery (24/26; 92 percent), compared with group 1 (2/15 and 10/15, respectively) and group 2 (6/18 and 12/18, respectively). Group 3 also manifested more extensive disease than groups 1 and 2 (judged by scoring system of Friesinger et al), with a score of 11 or more in 18 of 26 patients. We conclude that marked depth of \"ischemic\" ST-segment depression aids in identifying that subgroup of the coronary population with severe coronary artery disease and, therefore, serves as a useful means of culling out patients with a potentially serious prognosis who might benefit from intensive diagnostic or therapeutic interventions."} {"id": "PMID:1277890", "title": "Postinfarctional ventricular septal rupture. Clinical approach and surgical results.", "content": "This study represents an analysis of 13 cases of ruptured interventricular septum occurring as a complication of myocardial infarction. The cases considered appeared to divide themselves into two groups. One group survived the septal rupture for weeks or months and underwent surgery in the chronic stage. The patients in the other group were diagnosed and underwent surgery in the acute stage because of clinical indications of a rapidly deteriorating situation. There were four serious complications resulting from extensive cardiac catheterization and angiographic procedures. Those patients who were diagnosed using bedside balloon-directed catheterization techniques had no serious complications. The data indicate that: (1) the diagnostic approach should be executed quickly and by simple methods; (2) it is possible to operate successfully upon these patients in the acute phase of their disease; and (3) because of the unpredictable course and rapid deterioration, these alternatives should be strongly considered.", "contents": "Postinfarctional ventricular septal rupture. Clinical approach and surgical results. This study represents an analysis of 13 cases of ruptured interventricular septum occurring as a complication of myocardial infarction. The cases considered appeared to divide themselves into two groups. One group survived the septal rupture for weeks or months and underwent surgery in the chronic stage. The patients in the other group were diagnosed and underwent surgery in the acute stage because of clinical indications of a rapidly deteriorating situation. There were four serious complications resulting from extensive cardiac catheterization and angiographic procedures. Those patients who were diagnosed using bedside balloon-directed catheterization techniques had no serious complications. The data indicate that: (1) the diagnostic approach should be executed quickly and by simple methods; (2) it is possible to operate successfully upon these patients in the acute phase of their disease; and (3) because of the unpredictable course and rapid deterioration, these alternatives should be strongly considered."} {"id": "PMID:1277891", "title": "Retroperitoneal air dissection associated with mechanical ventilation.", "content": "The radiologic patterns, etiology, and possible consequences of gas dissection into the retroperitoneal space from pulmonary sources are reviewed in three patients requiring mechanical ventilation. Airway disruption appears to be related to peak airway pressures, underlying pulmonary disease, and the patient's hemodynamic condition and may cause different forms of interstitial emphysema and air embolization, which may lead to severe respiratory or circulatory dysfunction. Gas migration to the retroperitoneum and, secondarily, into the peritoneal cavity should be considered in the differential diagnosis of free intra-abdominal gas.", "contents": "Retroperitoneal air dissection associated with mechanical ventilation. The radiologic patterns, etiology, and possible consequences of gas dissection into the retroperitoneal space from pulmonary sources are reviewed in three patients requiring mechanical ventilation. Airway disruption appears to be related to peak airway pressures, underlying pulmonary disease, and the patient's hemodynamic condition and may cause different forms of interstitial emphysema and air embolization, which may lead to severe respiratory or circulatory dysfunction. Gas migration to the retroperitoneum and, secondarily, into the peritoneal cavity should be considered in the differential diagnosis of free intra-abdominal gas."} {"id": "PMID:1277892", "title": "Treatment of anaerobic pulmonary infections; carbenicillin compared to clindamycin and gentamicin.", "content": "Twenty-three patients with anaerobic infections of the lung were treated with either two antibiotics, clindamycin and gentamicin (11 patients) or with a single antibiotic, carbenicillin (12 patients). Cultures were obtained prior to therapy, either by transtracheal needle aspiration (17 patients) or thoracocentesis (six patients). Anaerobic bacteria were found in all. Fifteen patients had aerobic and facultative bacteria in addition. The anerobic isolates were peptostreptococci (12), peptococci (12), Bacteroides organisms (eight), clostridia (three), actinomycetes (two), eubacteria (one), and fusobacteria (one). Aerobes included streptococci (nine), enterococci (seven), Neisseria organisms (two), Klebsiella organisms (one), Citrobacter organisms (one), Pseudomonas organisms (one), Mycobacterium tuberculosis (two), and Nocardia (one). The two patients with pulmonary tuberculosis with anaerobic and superinfection received antituberculosis chemotherapy in addition. Therapeutic response was considered excellent in both groups. This suggests that carbenicillin may be used as a single antibiotic in the treatment of anaerobic and mixed infections of the lung.", "contents": "Treatment of anaerobic pulmonary infections; carbenicillin compared to clindamycin and gentamicin. Twenty-three patients with anaerobic infections of the lung were treated with either two antibiotics, clindamycin and gentamicin (11 patients) or with a single antibiotic, carbenicillin (12 patients). Cultures were obtained prior to therapy, either by transtracheal needle aspiration (17 patients) or thoracocentesis (six patients). Anaerobic bacteria were found in all. Fifteen patients had aerobic and facultative bacteria in addition. The anerobic isolates were peptostreptococci (12), peptococci (12), Bacteroides organisms (eight), clostridia (three), actinomycetes (two), eubacteria (one), and fusobacteria (one). Aerobes included streptococci (nine), enterococci (seven), Neisseria organisms (two), Klebsiella organisms (one), Citrobacter organisms (one), Pseudomonas organisms (one), Mycobacterium tuberculosis (two), and Nocardia (one). The two patients with pulmonary tuberculosis with anaerobic and superinfection received antituberculosis chemotherapy in addition. Therapeutic response was considered excellent in both groups. This suggests that carbenicillin may be used as a single antibiotic in the treatment of anaerobic and mixed infections of the lung."} {"id": "PMID:1277893", "title": "Deaths and complications associated with fiberoptic bronchoscopy.", "content": "A questionnaire was sent to 1,041 owners of fiberoptic bronchoscopes requesting data about complications of bronchoscopic examination; 323 (31 percent) of the questionnaires were returned. From approximately 48,000 procedures, ten deaths were reported and are described. Information about two additional deaths not obtained from data on the questionnaires is also included. All patients who died had either myocardial disease, severe chronic pulmonary disease, serious pneumonia, or cancer. Two deaths were associated with evidence on necropsy of fresh myocardial infarctions that had been unsuspected prior to the procedure. Two deaths occurred after administration of local anesthesia prior to bronchoscopic examination. Two were patients who previously had slowly hemorrhaging tumors that hemorrhaged massively following, respectively, forceps biopsy and saline lavage. Four brushes broke off in bronchi. Ten cardiac arrests and 41 life-threatening reactions to anesthesia also occurred.", "contents": "Deaths and complications associated with fiberoptic bronchoscopy. A questionnaire was sent to 1,041 owners of fiberoptic bronchoscopes requesting data about complications of bronchoscopic examination; 323 (31 percent) of the questionnaires were returned. From approximately 48,000 procedures, ten deaths were reported and are described. Information about two additional deaths not obtained from data on the questionnaires is also included. All patients who died had either myocardial disease, severe chronic pulmonary disease, serious pneumonia, or cancer. Two deaths were associated with evidence on necropsy of fresh myocardial infarctions that had been unsuspected prior to the procedure. Two deaths occurred after administration of local anesthesia prior to bronchoscopic examination. Two were patients who previously had slowly hemorrhaging tumors that hemorrhaged massively following, respectively, forceps biopsy and saline lavage. Four brushes broke off in bronchi. Ten cardiac arrests and 41 life-threatening reactions to anesthesia also occurred."} {"id": "PMID:1277894", "title": "Diagnostic accuracy in lung cancer; comparison of techniques used in association with flexible fiberoptic bronchoscopy.", "content": "Flexible fiberoptic bronchoscopic examination was performed 254 times in 228 patients in a prospective study to determine what specimens would give the greatest yield in the diagnosis of lung cancer. In addition, we questioned whether postbronchoscopic sputum specimens were still the most accurate method of diagnosing lung cancer, as they had been when only the rigid bronchoscope was available. Material for cytopathologic examination was obtained from bronchial brushings, bronchial biopsy, bronchial brushings in saline solution, bronchial washings, and three postbronchoscopie sputum specimens. In the latter part of the study, patients with peripheral tumors were studied with the aid of biplane fluoroscopic techniques. Bronchial brushings and bronchial biopsy each yielded the highest percentage of positive specimens (65 percent); postbronchoscopic sputum specimens were less frequently positive (40 percent). The combination of bronchial brushings and bronchial biopsies gave the optimum overall accuracy (79 percent). Bronchial washings and postbronchoscopic sputum specimens did not add significantly to diagnostic yield, and we conclude that they should no longer be part of the diagnostic procedures routinely ordered. In peripheral lesions, diagnostic accuracy was greatly enhanced in the cases where biplane fluoroscopic techniques were employed.", "contents": "Diagnostic accuracy in lung cancer; comparison of techniques used in association with flexible fiberoptic bronchoscopy. Flexible fiberoptic bronchoscopic examination was performed 254 times in 228 patients in a prospective study to determine what specimens would give the greatest yield in the diagnosis of lung cancer. In addition, we questioned whether postbronchoscopic sputum specimens were still the most accurate method of diagnosing lung cancer, as they had been when only the rigid bronchoscope was available. Material for cytopathologic examination was obtained from bronchial brushings, bronchial biopsy, bronchial brushings in saline solution, bronchial washings, and three postbronchoscopie sputum specimens. In the latter part of the study, patients with peripheral tumors were studied with the aid of biplane fluoroscopic techniques. Bronchial brushings and bronchial biopsy each yielded the highest percentage of positive specimens (65 percent); postbronchoscopic sputum specimens were less frequently positive (40 percent). The combination of bronchial brushings and bronchial biopsies gave the optimum overall accuracy (79 percent). Bronchial washings and postbronchoscopic sputum specimens did not add significantly to diagnostic yield, and we conclude that they should no longer be part of the diagnostic procedures routinely ordered. In peripheral lesions, diagnostic accuracy was greatly enhanced in the cases where biplane fluoroscopic techniques were employed."} {"id": "PMID:1277895", "title": "Superimposition of transmural infarction following acute subendocardial infarction; how frequent?", "content": "Thirty-five consecutive patients with acute subendocardial infarction admitted to the coronary care unit during a 15-month period were identified and analyzed for location of infarction, and for the in-hospital course in terms of recurrent chest pain, the occurrence of a second infarction, and the clinical status at the end of hospitalization. Thirteen patients developed a transmural infarction sometime between 3 and 21 days (average, ten days) after the initial subendocardial infarction. The transmural infarction was defined by a separate episode of severe and prolonged chest pain, late development of QRS alteration, and an appropriate elevation of the creatine phosphokinase concentration. Our experience with acute subendocardial infarction, hertofore regarded as a relatively benign event, indicates that the immediate prognosis of the patient who sustains his first episode of subendocardial infarction is not at all benign, and, indeed, subendocardial infarction frequently heralds transmural infarction within the acute phase of the disease.", "contents": "Superimposition of transmural infarction following acute subendocardial infarction; how frequent? Thirty-five consecutive patients with acute subendocardial infarction admitted to the coronary care unit during a 15-month period were identified and analyzed for location of infarction, and for the in-hospital course in terms of recurrent chest pain, the occurrence of a second infarction, and the clinical status at the end of hospitalization. Thirteen patients developed a transmural infarction sometime between 3 and 21 days (average, ten days) after the initial subendocardial infarction. The transmural infarction was defined by a separate episode of severe and prolonged chest pain, late development of QRS alteration, and an appropriate elevation of the creatine phosphokinase concentration. Our experience with acute subendocardial infarction, hertofore regarded as a relatively benign event, indicates that the immediate prognosis of the patient who sustains his first episode of subendocardial infarction is not at all benign, and, indeed, subendocardial infarction frequently heralds transmural infarction within the acute phase of the disease."} {"id": "PMID:1277896", "title": "Influence of alterations in the hematocrit upon the P wave and the QRS complex.", "content": "The net effect of intracavitary blood mass on cardiac dipole is believed to augment its radial components and reduce the tangential components. Commonly known as the Brody effect, it results from the lower resistivity of intracavitary blood mass as compared to the surrounding tissues (the short-circuiting effect). Thus, an increase in hematocrit should reduce and a decrease in hematocrit augment the Brody effect. It has generally been assumed that the initial portion of the process of ventricular depolarization and the left maximal spatial vector (LMSV) represent the radial components, while the terminal portion of the process of ventricular depolarization and the right maximal spatial vector (RMSV) represents the tangential components of cardiac dipole. Furthermore, the atrial accession is believed to be tangential. Based on this Brody effect, it is anticipated that an improvement of anemia, as indicated by an increase in hematocrit, would tend to reduce the initial portion of the QRS, and LMSV, but enhance the terminal portion of the QRS, and the P-wave amplitude; however, the results of this study were not in agreement with such predictions. With an improvement of anemia, a significant number of cases showed no essential changes in these electrocardiographic factors or even showed reactions oppisite to the Brody effect. This probably indicates that there are many other factors which might modify the Brody effect.", "contents": "Influence of alterations in the hematocrit upon the P wave and the QRS complex. The net effect of intracavitary blood mass on cardiac dipole is believed to augment its radial components and reduce the tangential components. Commonly known as the Brody effect, it results from the lower resistivity of intracavitary blood mass as compared to the surrounding tissues (the short-circuiting effect). Thus, an increase in hematocrit should reduce and a decrease in hematocrit augment the Brody effect. It has generally been assumed that the initial portion of the process of ventricular depolarization and the left maximal spatial vector (LMSV) represent the radial components, while the terminal portion of the process of ventricular depolarization and the right maximal spatial vector (RMSV) represents the tangential components of cardiac dipole. Furthermore, the atrial accession is believed to be tangential. Based on this Brody effect, it is anticipated that an improvement of anemia, as indicated by an increase in hematocrit, would tend to reduce the initial portion of the QRS, and LMSV, but enhance the terminal portion of the QRS, and the P-wave amplitude; however, the results of this study were not in agreement with such predictions. With an improvement of anemia, a significant number of cases showed no essential changes in these electrocardiographic factors or even showed reactions oppisite to the Brody effect. This probably indicates that there are many other factors which might modify the Brody effect."} {"id": "PMID:1277897", "title": "Recurrent reciprocating tachycardias in the Wolff-Parkinson-White syndrome; control by the use of a scanning pacemaker.", "content": "Frequent episodes of arrhythmias in patients with the Wolff-Parkinson-White syndrome are sometimes unresponsive to medical management. Recent emphasis has been placed on the role of surgery as a means of effectively controlling these patients' tachyarrhythmias; however, in some patients the use of permanent pacing has been espoused as an effective means of controlling arrhythmias. This report documents the efficacy of a new pacemaker with rate-scanning features, which offers significant technical advantages. Subsequent follow-up has documented the efficacy of this unit in the management of a young woman with type-A Wolff-Parkinson-White syndrome and previously intractable arrhythmias.", "contents": "Recurrent reciprocating tachycardias in the Wolff-Parkinson-White syndrome; control by the use of a scanning pacemaker. Frequent episodes of arrhythmias in patients with the Wolff-Parkinson-White syndrome are sometimes unresponsive to medical management. Recent emphasis has been placed on the role of surgery as a means of effectively controlling these patients' tachyarrhythmias; however, in some patients the use of permanent pacing has been espoused as an effective means of controlling arrhythmias. This report documents the efficacy of a new pacemaker with rate-scanning features, which offers significant technical advantages. Subsequent follow-up has documented the efficacy of this unit in the management of a young woman with type-A Wolff-Parkinson-White syndrome and previously intractable arrhythmias."} {"id": "PMID:1277899", "title": "Intraventricular free wall dissection causing acute interventricular communication with intact septum in myocardial infarction.", "content": "This report delineates a previously unrecognized complication of acute myocardial infarction, an intraventricular wall dissection producing interventricular communication without septal perforation. The clinical, hemodynamic, and pathologic features of this unique condition are documented, as well as the factors important in the mechanism of its production.", "contents": "Intraventricular free wall dissection causing acute interventricular communication with intact septum in myocardial infarction. This report delineates a previously unrecognized complication of acute myocardial infarction, an intraventricular wall dissection producing interventricular communication without septal perforation. The clinical, hemodynamic, and pathologic features of this unique condition are documented, as well as the factors important in the mechanism of its production."} {"id": "PMID:1277900", "title": "Patent ductus arteriosus with hypoplastic lung.", "content": "A median sternotomy approach was used for closure of patent ductus arteriosus associated with a hypoplastic right lung. The anterior approach to the left ductus is indicated if left thoracotomy is contraindicated.", "contents": "Patent ductus arteriosus with hypoplastic lung. A median sternotomy approach was used for closure of patent ductus arteriosus associated with a hypoplastic right lung. The anterior approach to the left ductus is indicated if left thoracotomy is contraindicated."} {"id": "PMID:1277901", "title": "Nocardia infection in a bronchopulmonary sequestration.", "content": "A case of intralobar bronchopulmonary sequestration is reported in which the sequestered lung was infected with Nocardia sp. Although recurrent pyogenic infections are common in pulmonary sequestrations, this is the first case report with documented nocardiosis.", "contents": "Nocardia infection in a bronchopulmonary sequestration. A case of intralobar bronchopulmonary sequestration is reported in which the sequestered lung was infected with Nocardia sp. Although recurrent pyogenic infections are common in pulmonary sequestrations, this is the first case report with documented nocardiosis."} {"id": "PMID:1277902", "title": "Detection of covert myocardial sarcoidosis by scalene node biopsy.", "content": "The antemortem diagnosis of myocardial sarcoidosis is rare in patients without overt signs of the disease. Two patients are presented to alert physicians to the value of early scalene node biopsy when sarcoidosis could be the cause of marked disturbances in cardiac conduction. The first patient, aged 29 years, had first, second, and third degree atrioventricular block and intermittent left and right bundle-branch block; the second, aged 59 years, had second degree atrioventricular block and complete right bundle-branch block. Both had diagnoses of sarcoidosis based on scalene node biopsy. The cardiac conductive disturbance improved, and the symptoms disappeared with steroid therapy.", "contents": "Detection of covert myocardial sarcoidosis by scalene node biopsy. The antemortem diagnosis of myocardial sarcoidosis is rare in patients without overt signs of the disease. Two patients are presented to alert physicians to the value of early scalene node biopsy when sarcoidosis could be the cause of marked disturbances in cardiac conduction. The first patient, aged 29 years, had first, second, and third degree atrioventricular block and intermittent left and right bundle-branch block; the second, aged 59 years, had second degree atrioventricular block and complete right bundle-branch block. Both had diagnoses of sarcoidosis based on scalene node biopsy. The cardiac conductive disturbance improved, and the symptoms disappeared with steroid therapy."} {"id": "PMID:1277903", "title": "Penetrating injury of the chest and coronary arteriovenous fistula.", "content": "An unusual case of coronary artery fistula, due to a stab wound in the chest in a 17-year-old male patient, with a resultant acute inferior myocardial infarction is presented. At surgery, complete transection of the right coronary artery was found, which formed a fistulous communication with both the right atrium and the right ventricle. The development of a continuous murmur in the period immediately after the injury, the absence of hemopericardium, and multiple cardiac-chamber involvements were unique features of the case. The inferior myocardial wall was akinetic due to infarction and did not improve following revascularization surgery. A brief review of the literature is also presented.", "contents": "Penetrating injury of the chest and coronary arteriovenous fistula. An unusual case of coronary artery fistula, due to a stab wound in the chest in a 17-year-old male patient, with a resultant acute inferior myocardial infarction is presented. At surgery, complete transection of the right coronary artery was found, which formed a fistulous communication with both the right atrium and the right ventricle. The development of a continuous murmur in the period immediately after the injury, the absence of hemopericardium, and multiple cardiac-chamber involvements were unique features of the case. The inferior myocardial wall was akinetic due to infarction and did not improve following revascularization surgery. A brief review of the literature is also presented."} {"id": "PMID:1277904", "title": "Esophagopleural fistula after pneumonectomy.", "content": "Rupture of the esophagus into the space left after pneumonectomy is a rare and often fatal complication. Esophagopleural fistulas occurred in three patients following pneumonectomy. After previous methods failed, two patients were successfully treated by using a one-stage procedure which included (1) suture closure of the fistula, (2) buttressing the repair with a viable, pedicled, two-rib intercostal-muscle flap, and (3) performing an extensive thoracoplasty with a continuous drip infusion of neomycin. Such a procedure offers the maximum opportunity for successful treatment of this catastrophic lesion.", "contents": "Esophagopleural fistula after pneumonectomy. Rupture of the esophagus into the space left after pneumonectomy is a rare and often fatal complication. Esophagopleural fistulas occurred in three patients following pneumonectomy. After previous methods failed, two patients were successfully treated by using a one-stage procedure which included (1) suture closure of the fistula, (2) buttressing the repair with a viable, pedicled, two-rib intercostal-muscle flap, and (3) performing an extensive thoracoplasty with a continuous drip infusion of neomycin. Such a procedure offers the maximum opportunity for successful treatment of this catastrophic lesion."} {"id": "PMID:1277905", "title": "Alternation of left ventricular performance with electrical alternans.", "content": "Systolic time intervals (STIs) were measured in a patient with massive pericardial effusion and electrical alternans. The total electromechanical systole and the left ventricular ejection time (LVET) were significantly shorter in beats following the smaller QRS complexes, while the pre-ejection time (PEP) was longer and the ratio of PEP/LVET larger. This beat-to-beat difference in the STIs suggests than an alternation in left ventricular performance accompanied the electrical alternans. After evacuation of the pericardial fluid, electrical alternans and STI alternation disappeared.", "contents": "Alternation of left ventricular performance with electrical alternans. Systolic time intervals (STIs) were measured in a patient with massive pericardial effusion and electrical alternans. The total electromechanical systole and the left ventricular ejection time (LVET) were significantly shorter in beats following the smaller QRS complexes, while the pre-ejection time (PEP) was longer and the ratio of PEP/LVET larger. This beat-to-beat difference in the STIs suggests than an alternation in left ventricular performance accompanied the electrical alternans. After evacuation of the pericardial fluid, electrical alternans and STI alternation disappeared."} {"id": "PMID:1277906", "title": "Mycobacterium szulgai; a new pathogen causing infection of the lung.", "content": "A case of infection with a newly described scotochromogenic mycobacterial species, Mycobacterium szulgai, is presented, and all the reported cases are summarized. The disease is characterized by its predominance in middle-aged men, the occurrence of cavitary pulmonary lesions, and a good response to triple-drug therapy. Sputum samples are usually positive on smear. Drug susceptibility studies show a greater degree of susceptibility to several antituberculosis drugs than the usual scotochromogen. Mycobacterium szulgai has frequently been confused with other atypical mycobacteria, but serologic and other laboratory characteristics are distinct and should allow proper identification.", "contents": "Mycobacterium szulgai; a new pathogen causing infection of the lung. A case of infection with a newly described scotochromogenic mycobacterial species, Mycobacterium szulgai, is presented, and all the reported cases are summarized. The disease is characterized by its predominance in middle-aged men, the occurrence of cavitary pulmonary lesions, and a good response to triple-drug therapy. Sputum samples are usually positive on smear. Drug susceptibility studies show a greater degree of susceptibility to several antituberculosis drugs than the usual scotochromogen. Mycobacterium szulgai has frequently been confused with other atypical mycobacteria, but serologic and other laboratory characteristics are distinct and should allow proper identification."} {"id": "PMID:1277907", "title": "Serial echocardiographic abnormalities in nonbacterial thrombotic endocarditis of the mitral valve.", "content": "This report describes the clinical course and serial echocardiographic abnormalities in a patient with nonbacterial thrombotic endocarditis and repeated embolic episodes. Serial echocardiograms revealed a mass of abnormal echoes on the anterior mitral leaflet and progressive restriction of mitral valvular motion. Cineangiographic studies demonstrated a large filling defect in the area of the mitral valve. Surgical intervention confirmed the presence of a large vegetation on the mitral valve. The surgical specimen consisted of a sterile, partially organized fibrin thrombus. The echocardiographic abnormalities are described and discussed in relation to the clinical and pathologic findings.", "contents": "Serial echocardiographic abnormalities in nonbacterial thrombotic endocarditis of the mitral valve. This report describes the clinical course and serial echocardiographic abnormalities in a patient with nonbacterial thrombotic endocarditis and repeated embolic episodes. Serial echocardiograms revealed a mass of abnormal echoes on the anterior mitral leaflet and progressive restriction of mitral valvular motion. Cineangiographic studies demonstrated a large filling defect in the area of the mitral valve. Surgical intervention confirmed the presence of a large vegetation on the mitral valve. The surgical specimen consisted of a sterile, partially organized fibrin thrombus. The echocardiographic abnormalities are described and discussed in relation to the clinical and pathologic findings."} {"id": "PMID:1277914", "title": "Persistence of the third heart sound after resection of the native mitral and tricuspid valves. Evidence against the valvular theory of third sound origin.", "content": "A patient is described with severe rheumatic mitral and tricuspid insufficiency in whom both atrioventricular valves with their chordae tendineae and papillary muscles were resected and replaced with Hancock porcine grafts. This would appear to be the second such patient reported and the first described in detail in whom the third heart sound persisted postoperation. This occurrence documents the fact that a third heart sound can occur in the absence of native atrioventricular valve leaflets and the major portions of the subvalvular supporting apparatus, and argues against the theory that the third heart sound is generated by either the valvular leaflets of the subvalvular apparatus.", "contents": "Persistence of the third heart sound after resection of the native mitral and tricuspid valves. Evidence against the valvular theory of third sound origin. A patient is described with severe rheumatic mitral and tricuspid insufficiency in whom both atrioventricular valves with their chordae tendineae and papillary muscles were resected and replaced with Hancock porcine grafts. This would appear to be the second such patient reported and the first described in detail in whom the third heart sound persisted postoperation. This occurrence documents the fact that a third heart sound can occur in the absence of native atrioventricular valve leaflets and the major portions of the subvalvular supporting apparatus, and argues against the theory that the third heart sound is generated by either the valvular leaflets of the subvalvular apparatus."} {"id": "PMID:1277922", "title": "Late thrombosis of the aortic Bjork-Shiley prosthesis. Its clinical recognition and management.", "content": "Seven cases of massive thrombosis of an aortic Bjork-Shiley prosthesis were encountered among 433 valvular implants. Four patients died before treatment could be instituted, and three underwent repeat surgery successfully. Anticoagulation therapy was probably well maintained in four, and poorly maintained in three patients. These cases illustrated the need for a high index of suspicion and prompt recognition of this complication in patients with Bjork-Shiley prostheses. The diagnosis of massive thrombosis should be suspected with the rapid onset of (1) signs of congestive heart failure, (2) absence or attenuation of valvular clicks, (3) aortic regurgitation, or (4) hemolytic anemia. Salvage of these patients requires emergency replacement of the thrombosed prosthesis or removal of the thrombus.", "contents": "Late thrombosis of the aortic Bjork-Shiley prosthesis. Its clinical recognition and management. Seven cases of massive thrombosis of an aortic Bjork-Shiley prosthesis were encountered among 433 valvular implants. Four patients died before treatment could be instituted, and three underwent repeat surgery successfully. Anticoagulation therapy was probably well maintained in four, and poorly maintained in three patients. These cases illustrated the need for a high index of suspicion and prompt recognition of this complication in patients with Bjork-Shiley prostheses. The diagnosis of massive thrombosis should be suspected with the rapid onset of (1) signs of congestive heart failure, (2) absence or attenuation of valvular clicks, (3) aortic regurgitation, or (4) hemolytic anemia. Salvage of these patients requires emergency replacement of the thrombosed prosthesis or removal of the thrombus."} {"id": "PMID:1277923", "title": "A comparison of spirometric values with subjects in standing and sitting positions.", "content": "Spirograms obtained from 235 subjects in standing and sitting positions revealed small differences for the forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). No statistically significant differences were found for the mean forced expiratory flow during the middle half of the FVC (FEF25-75%, or maximal midexpiratory flow) and FEV1/FVC. Sitting values were, on the average, higher for determinations greater than FVC of 2.14 L, FEV1 of 1.68 L, FEF25-75% of 2.16 L/sec, and FEV1/FVC of 75.7 percent. On the average, subjects with less than these values performed slightly better in the standing position.", "contents": "A comparison of spirometric values with subjects in standing and sitting positions. Spirograms obtained from 235 subjects in standing and sitting positions revealed small differences for the forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). No statistically significant differences were found for the mean forced expiratory flow during the middle half of the FVC (FEF25-75%, or maximal midexpiratory flow) and FEV1/FVC. Sitting values were, on the average, higher for determinations greater than FVC of 2.14 L, FEV1 of 1.68 L, FEF25-75% of 2.16 L/sec, and FEV1/FVC of 75.7 percent. On the average, subjects with less than these values performed slightly better in the standing position."} {"id": "PMID:1277925", "title": "Quantitative levels of immunoglobulin E in advanced tuberculosis.", "content": "Quantitative levels of immunoglobulin E (IgE) were determined in samples of sera obtained from 29 patients with proven moderate to far-advanced tuberculosis. The sensitive radioimmunoassay test for IgE was used. Statistical analysis of the results revealed no difference in IgE values as compared to a control group of normal sera. In contrast to other chronic pulmonary infections, such as bronchopulmonary aspergillosis, the IgE level in pulmonary tuberculous infection is of no diagnostic significance. Simultaneous determination of levels of immunoglobulins G, A, M, and D (IgG, IgA, IgM, IgD) in these same sera by radial immunodiffusion showed elevated IgG and lowered IgM levels in the tuberculous patients, confirming previous studies. The significance of these alterations in immunoglobulin levels is unclear and may represent a secondary phenomenon rather than a primary host response.", "contents": "Quantitative levels of immunoglobulin E in advanced tuberculosis. Quantitative levels of immunoglobulin E (IgE) were determined in samples of sera obtained from 29 patients with proven moderate to far-advanced tuberculosis. The sensitive radioimmunoassay test for IgE was used. Statistical analysis of the results revealed no difference in IgE values as compared to a control group of normal sera. In contrast to other chronic pulmonary infections, such as bronchopulmonary aspergillosis, the IgE level in pulmonary tuberculous infection is of no diagnostic significance. Simultaneous determination of levels of immunoglobulins G, A, M, and D (IgG, IgA, IgM, IgD) in these same sera by radial immunodiffusion showed elevated IgG and lowered IgM levels in the tuberculous patients, confirming previous studies. The significance of these alterations in immunoglobulin levels is unclear and may represent a secondary phenomenon rather than a primary host response."} {"id": "PMID:1277926", "title": "Both direct and neurally mediated components of the chronotropic actions of aminophylline.", "content": "Aminophylline was selectively perfused through either the sinus node or through the AV (atrioventricular) junction of 35 intact canine hearts in situ. The positive chronotropic action observed was equally powerful in accelerating either sinus rhythm (50 +/- 8 percent increment) or AV junctional rhythm (55 +/- 10 percent increment). This positive chronotropic effect has at least three distinct components: a major direct action on autonomic centers, a lesser effect due to local catecholamine release, and a part due to peripheral vagolytic action.", "contents": "Both direct and neurally mediated components of the chronotropic actions of aminophylline. Aminophylline was selectively perfused through either the sinus node or through the AV (atrioventricular) junction of 35 intact canine hearts in situ. The positive chronotropic action observed was equally powerful in accelerating either sinus rhythm (50 +/- 8 percent increment) or AV junctional rhythm (55 +/- 10 percent increment). This positive chronotropic effect has at least three distinct components: a major direct action on autonomic centers, a lesser effect due to local catecholamine release, and a part due to peripheral vagolytic action."} {"id": "PMID:1277928", "title": "The diagnosis of pleural effusion by ultrasonic and radiologic techniques.", "content": "The value of the A-mode ultrasonic technique and the radiologic method in the diagnosis of pleural effusion was assessed in 116 patients with diseases of the pleura. Ultrasonic and radiologic examinations, as well as needle punctures, were performed, and the results were compared statistically. The pleural fluid was detected by ultrasound in 93 percent (74) and by radiologic examination in 83 percent (66) of the 80 cases with such fluid. The absence of fluid was established by ultrasound in 89 percent (32/36) and by radiologic examination in 61 percent (22/36). For the first time the superiority of the ultrasonic method over the radiologic one was demonstrated, and the difference was most obvious in cases of small pleural effusion. Ultrasound permitted the detection of very small amounts (even 3 to 5 ml) of loculated pleural fluid. In contrast to the radiologic method, ultrasound permitted easy differentiation between loculated pleural fluid and pleural thickenings. The ultrasonic method appeared especially useful in the accurate localization and precise indicating of the site for needle aspiration of even the smallest fluid collections. It made possible thoracocentesis in 94 percent (154) of 163 instances. The practical value of the ultrasonic method, both in establishing diagnosis and in treatment, is emphasized.", "contents": "The diagnosis of pleural effusion by ultrasonic and radiologic techniques. The value of the A-mode ultrasonic technique and the radiologic method in the diagnosis of pleural effusion was assessed in 116 patients with diseases of the pleura. Ultrasonic and radiologic examinations, as well as needle punctures, were performed, and the results were compared statistically. The pleural fluid was detected by ultrasound in 93 percent (74) and by radiologic examination in 83 percent (66) of the 80 cases with such fluid. The absence of fluid was established by ultrasound in 89 percent (32/36) and by radiologic examination in 61 percent (22/36). For the first time the superiority of the ultrasonic method over the radiologic one was demonstrated, and the difference was most obvious in cases of small pleural effusion. Ultrasound permitted the detection of very small amounts (even 3 to 5 ml) of loculated pleural fluid. In contrast to the radiologic method, ultrasound permitted easy differentiation between loculated pleural fluid and pleural thickenings. The ultrasonic method appeared especially useful in the accurate localization and precise indicating of the site for needle aspiration of even the smallest fluid collections. It made possible thoracocentesis in 94 percent (154) of 163 instances. The practical value of the ultrasonic method, both in establishing diagnosis and in treatment, is emphasized."} {"id": "PMID:1277930", "title": "Pleural calcification associated with exposure to chrysotile asbestos in southeast Turkey.", "content": "In this study, pleural calcifications prevailing in the inhabitants of some villages and towns around Diyarbakir, a city in southeast Turkey, have been found to be caused by the inhalation of chrysotile asbestos, the mineral commonly used indiscriminately to paint the walls and floors of houses. There were no industrial establishments in the area, except some local mining, and asbestos deposits were even not included on the mining map of the country. Chest roentgenograms from the Chest Hospital and the tuberculosis dispensaries were screened: and, additionally, 15,239 photofluorograms were obtained during a survey. Of all these, 511 patients were found to have pleural calcifications, some with pericardial and diaphragmatic involvement. Forty-four percent (28) of the 64 patients who had examinations of samples of their sputa had asbestos bodies, and asbestosis was also induced in rabbits by administration of the raw material.", "contents": "Pleural calcification associated with exposure to chrysotile asbestos in southeast Turkey. In this study, pleural calcifications prevailing in the inhabitants of some villages and towns around Diyarbakir, a city in southeast Turkey, have been found to be caused by the inhalation of chrysotile asbestos, the mineral commonly used indiscriminately to paint the walls and floors of houses. There were no industrial establishments in the area, except some local mining, and asbestos deposits were even not included on the mining map of the country. Chest roentgenograms from the Chest Hospital and the tuberculosis dispensaries were screened: and, additionally, 15,239 photofluorograms were obtained during a survey. Of all these, 511 patients were found to have pleural calcifications, some with pericardial and diaphragmatic involvement. Forty-four percent (28) of the 64 patients who had examinations of samples of their sputa had asbestos bodies, and asbestosis was also induced in rabbits by administration of the raw material."} {"id": "PMID:1277931", "title": "Doppler ultrasonic assessment of aortic stenosis by analysis of axillary arterial blood velocity upstroke time.", "content": "Rate-corrected velocity upstroke time (VUT) was calculated from analogue Doppler ultrasound recordings of axillary artery blood flow velocity in 25 patients with aortic stenosis documented by cardiac catheterization and in 14 normal individuals. The mean VUT in normal individuals was 0.11 +/- 0.02 second (+/- 1 SD), which was significantly lower than that of patients with aortic stenosis: 0.15 +/- 0.05 second (P less than 0.005). The VUT correlated with the aortic valve index and the aortic valve mean pressure gradient with correlation coefficients of 0.62 and 0.64, respectively (P less than 0.005). Arterial blood flow velocity assessment by Doppler ultrasound may be a useful noninvasive technique to evaluate patients with aortic valve disease.", "contents": "Doppler ultrasonic assessment of aortic stenosis by analysis of axillary arterial blood velocity upstroke time. Rate-corrected velocity upstroke time (VUT) was calculated from analogue Doppler ultrasound recordings of axillary artery blood flow velocity in 25 patients with aortic stenosis documented by cardiac catheterization and in 14 normal individuals. The mean VUT in normal individuals was 0.11 +/- 0.02 second (+/- 1 SD), which was significantly lower than that of patients with aortic stenosis: 0.15 +/- 0.05 second (P less than 0.005). The VUT correlated with the aortic valve index and the aortic valve mean pressure gradient with correlation coefficients of 0.62 and 0.64, respectively (P less than 0.005). Arterial blood flow velocity assessment by Doppler ultrasound may be a useful noninvasive technique to evaluate patients with aortic valve disease."} {"id": "PMID:1277936", "title": "Aortico-left ventricular tunnel. Recognition and repair in infancy.", "content": "An infant with an aortico-left ventricular tunnel underwent surgery at the age of five months. There was clinical and electrocardiographic improvement, and postoperative cardiac catheterization demonstrated obliteration of the aortic end of the tunnel, normalization of systemic pulse pressure, mild residual aortic valvular insufficiency, and a decrease in the left ventricular end-diastolic volume index. Early surgery may limit the progression of aortic valvular insufficiency secondary to turbulent aortic-root blood flow.", "contents": "Aortico-left ventricular tunnel. Recognition and repair in infancy. An infant with an aortico-left ventricular tunnel underwent surgery at the age of five months. There was clinical and electrocardiographic improvement, and postoperative cardiac catheterization demonstrated obliteration of the aortic end of the tunnel, normalization of systemic pulse pressure, mild residual aortic valvular insufficiency, and a decrease in the left ventricular end-diastolic volume index. Early surgery may limit the progression of aortic valvular insufficiency secondary to turbulent aortic-root blood flow."} {"id": "PMID:1277937", "title": "Severe coarctation of the aorta with pulmonary edema. An unusual presentation of a traumatic aortic aneurysm.", "content": "A patient with an unrecognized rupture of the ascending aorta developed severe pulmonary edema three weeks following the initial injury. This is a distinctly unusual manifestation of this injury. Emergency resection of the traumatic aneurysm was required to reverse the rapidly deteriorating clinical situation. The early recognition and surgical treatment of this lesion would have avoided this complication.", "contents": "Severe coarctation of the aorta with pulmonary edema. An unusual presentation of a traumatic aortic aneurysm. A patient with an unrecognized rupture of the ascending aorta developed severe pulmonary edema three weeks following the initial injury. This is a distinctly unusual manifestation of this injury. Emergency resection of the traumatic aneurysm was required to reverse the rapidly deteriorating clinical situation. The early recognition and surgical treatment of this lesion would have avoided this complication."} {"id": "PMID:1277938", "title": "Esophagocolic anastomotic stricture repaired twelve years after original interposition.", "content": "Successful resection of a long, tight, unyielding cervical esophagocolic anastomosis with mobilization of the colon interposition transplant through a sternal splitting incision 12 years after the primary surgery is reported. The colon transplant with its vascular bundle was dissected with less difficulty than expected and 5 cm of increased length was obtained to make a new neck anastomosis without tension.", "contents": "Esophagocolic anastomotic stricture repaired twelve years after original interposition. Successful resection of a long, tight, unyielding cervical esophagocolic anastomosis with mobilization of the colon interposition transplant through a sternal splitting incision 12 years after the primary surgery is reported. The colon transplant with its vascular bundle was dissected with less difficulty than expected and 5 cm of increased length was obtained to make a new neck anastomosis without tension."} {"id": "PMID:1277939", "title": "Atrial fibrillation developing in the acute phase of myocardial infarction. Prognostic implications.", "content": "Atrial fibrillation was observed in 39 (11 percent) of 350 instances of acute myocardial infarction. The mortality among these patients was 41 percent (16/39). Atrial fibrillation was more common in patients with undetermined infarctions and in older people. As opposed to death rates close to 50 percent among patients with anterior, combined, and undetermined infarctions, the presence of atrial fibrillation did not affect the mortality among patients with inferior infarctions (10 percent, 1/10). Ventricular rates higher than 120 beats per minute and duration of the arrhythmia longer than six hours were not associated with increased mortality. Hemodynamic failure was present in almost all of the cases and preceded the arrhythmia in most of them. It is concluded that different mechanisms are responsible for the production of atrial fibrillation in the setting of acute myocardial infarction, and the prognosis of the patient is related to the mechanism of production and not to the arrhythmia itself.", "contents": "Atrial fibrillation developing in the acute phase of myocardial infarction. Prognostic implications. Atrial fibrillation was observed in 39 (11 percent) of 350 instances of acute myocardial infarction. The mortality among these patients was 41 percent (16/39). Atrial fibrillation was more common in patients with undetermined infarctions and in older people. As opposed to death rates close to 50 percent among patients with anterior, combined, and undetermined infarctions, the presence of atrial fibrillation did not affect the mortality among patients with inferior infarctions (10 percent, 1/10). Ventricular rates higher than 120 beats per minute and duration of the arrhythmia longer than six hours were not associated with increased mortality. Hemodynamic failure was present in almost all of the cases and preceded the arrhythmia in most of them. It is concluded that different mechanisms are responsible for the production of atrial fibrillation in the setting of acute myocardial infarction, and the prognosis of the patient is related to the mechanism of production and not to the arrhythmia itself."} {"id": "PMID:1277940", "title": "Subepicardial infarction, myocardial impression, and ventricular penetration by sutureless electrode and leads.", "content": "Postmortem examination two weeks following implantation of a demand pacemaker with sutureless electrodes demonstrated that (1) the loops of intrapericardial electrode leads indented the myocardium and produced a circumscribed area of subepicardial necrosis, and (2) one of the electrode coils protruded into the right ventricular cavity. The use of extrapericardial electrode leads and left ventricular implantation sites should avoid these problems.", "contents": "Subepicardial infarction, myocardial impression, and ventricular penetration by sutureless electrode and leads. Postmortem examination two weeks following implantation of a demand pacemaker with sutureless electrodes demonstrated that (1) the loops of intrapericardial electrode leads indented the myocardium and produced a circumscribed area of subepicardial necrosis, and (2) one of the electrode coils protruded into the right ventricular cavity. The use of extrapericardial electrode leads and left ventricular implantation sites should avoid these problems."} {"id": "PMID:1277941", "title": "Systemic arteriovenous fistula simulating severe valvular aortic stenosis.", "content": "A patient with a renal arteriovenous fistula is described. She was though to have valvular aortic stenosis because of a history of rheumatic fever, symptoms of congestive heart failure and syncope, and the presence of a harsh systolic murmur with a thrill in the aortic area. Cardiac catheterization revealed a left-to-right shunt of 8.7 L/min. Ligation of the fistula resulted in complete relief of the symptoms and attenuation of the murmur.", "contents": "Systemic arteriovenous fistula simulating severe valvular aortic stenosis. A patient with a renal arteriovenous fistula is described. She was though to have valvular aortic stenosis because of a history of rheumatic fever, symptoms of congestive heart failure and syncope, and the presence of a harsh systolic murmur with a thrill in the aortic area. Cardiac catheterization revealed a left-to-right shunt of 8.7 L/min. Ligation of the fistula resulted in complete relief of the symptoms and attenuation of the murmur."} {"id": "PMID:1277942", "title": "Pneumonitis due to Corynebacterium equi.", "content": "Corynebacterium equi, a known cause of pneumonitis in foals, calves, and swine, was isolated from the sputum and bronchial washings of a child with pneumonitis and leukemia. Clinical improvement followed the administration of chloramphenicol, and cultures of sputum specimens were sterile until relapse occurred after antibiotic therapy was terminated. Cure was achieved with a second course of chloramphenicol therapy. Corynebacterium equi was not isolated from 1,181 samples of sputum from other immunosuppressed children with cancer.", "contents": "Pneumonitis due to Corynebacterium equi. Corynebacterium equi, a known cause of pneumonitis in foals, calves, and swine, was isolated from the sputum and bronchial washings of a child with pneumonitis and leukemia. Clinical improvement followed the administration of chloramphenicol, and cultures of sputum specimens were sterile until relapse occurred after antibiotic therapy was terminated. Cure was achieved with a second course of chloramphenicol therapy. Corynebacterium equi was not isolated from 1,181 samples of sputum from other immunosuppressed children with cancer."} {"id": "PMID:1277943", "title": "Echocardiographic diagnosis of a stuck Bjork-Shiley aortic valve prosthesis.", "content": "A 55-year-old man who had been asymptomatic after replacement of his aortic valve with a Bjork-Shiley prosthesis, suddenly developed heart failure. The clinical suspicion of prosthetic malfunction was not only confirmed, but specified as being a stuck disc secondary to a large thrombus. Surgical removal of the clot resulted in restoration of normal function and return to the expected findings on echocardiogram. The value of echocardiography in such instances, as well as in routinely following-up patients with prostheses postoperatively, is emphasized.", "contents": "Echocardiographic diagnosis of a stuck Bjork-Shiley aortic valve prosthesis. A 55-year-old man who had been asymptomatic after replacement of his aortic valve with a Bjork-Shiley prosthesis, suddenly developed heart failure. The clinical suspicion of prosthetic malfunction was not only confirmed, but specified as being a stuck disc secondary to a large thrombus. Surgical removal of the clot resulted in restoration of normal function and return to the expected findings on echocardiogram. The value of echocardiography in such instances, as well as in routinely following-up patients with prostheses postoperatively, is emphasized."} {"id": "PMID:1277947", "title": "Periodic review of foster care: a brief national assessment.", "content": "A survey of statewide public agencies shows that a majority of states have some form of judicial or administrative periodic review, although few have both. The organizational level of authority and degree of foster care specialization of agencies are positively correlated with administrative review and negatively correlated with judicial review.", "contents": "Periodic review of foster care: a brief national assessment. A survey of statewide public agencies shows that a majority of states have some form of judicial or administrative periodic review, although few have both. The organizational level of authority and degree of foster care specialization of agencies are positively correlated with administrative review and negatively correlated with judicial review."} {"id": "PMID:1277950", "title": "Percutaneous third ventriculostomy: experience and technique.", "content": "A series of stereotaxic percutaneous third ventriculostomies has been carried out on 46 shunt-dependent hydrocephalic children. The technique and results are presented. The advantages of this procedure over the open craniotomy type are discussed. There has been low morbidity and one mortality. The necessity of preoperative shunting to provide a 'slack brain' is emphasized.", "contents": "Percutaneous third ventriculostomy: experience and technique. A series of stereotaxic percutaneous third ventriculostomies has been carried out on 46 shunt-dependent hydrocephalic children. The technique and results are presented. The advantages of this procedure over the open craniotomy type are discussed. There has been low morbidity and one mortality. The necessity of preoperative shunting to provide a 'slack brain' is emphasized."} {"id": "PMID:1277951", "title": "Measurement of respiration in Arnold-Chiari malformation.", "content": "Respiratory distress occurs in infants with myelomeningocele and Arnold-Chiari malformation. It is difficult to measure it because of the small volume exchanged and the lack of cooperation of infants. Existing equipment had to be modified to do so by decreasing the dead space and reducing the bulkiness of the sensing device. In infants with tracheostomies, a continuous flow of gas was applied to reduce the dead space. In infants without tracheostomies, a continuous flow of gas was applied, but the mask was too bulky to seal around the baby's face. A nose-piece pneumotachograph was developed to alleviate the problem. Respiration was measured in 15 patients with myelomeningocele and hydrocephalus from 1 day to 5 months of age. After gas was administered, they breathed 38.5 times a minute with a tidal volume of 6.25 ml/kg, producing a minute ventilation of 0.2541/min/kg. After administration of 5 per cent CO2-95 per cent O2, respiratory frequency rose to 47 breaths a minute, with a tidal volume of 8.8 ml/kg, producing a minute ventilation of 0.4101/min/kg, comparable to that of normal infants.", "contents": "Measurement of respiration in Arnold-Chiari malformation. Respiratory distress occurs in infants with myelomeningocele and Arnold-Chiari malformation. It is difficult to measure it because of the small volume exchanged and the lack of cooperation of infants. Existing equipment had to be modified to do so by decreasing the dead space and reducing the bulkiness of the sensing device. In infants with tracheostomies, a continuous flow of gas was applied to reduce the dead space. In infants without tracheostomies, a continuous flow of gas was applied, but the mask was too bulky to seal around the baby's face. A nose-piece pneumotachograph was developed to alleviate the problem. Respiration was measured in 15 patients with myelomeningocele and hydrocephalus from 1 day to 5 months of age. After gas was administered, they breathed 38.5 times a minute with a tidal volume of 6.25 ml/kg, producing a minute ventilation of 0.2541/min/kg. After administration of 5 per cent CO2-95 per cent O2, respiratory frequency rose to 47 breaths a minute, with a tidal volume of 8.8 ml/kg, producing a minute ventilation of 0.4101/min/kg, comparable to that of normal infants."} {"id": "PMID:1277952", "title": "Diagnosis and management of skeletal metastases from cerebellar medulloblastoma.", "content": "Four cases of cerebellar medulloblastoma with skeletal metastases have been described. Extracranial metastases from this tumour are extremely rare but the skeleton is the site most commonly involved. The metastases did not occur after ventriculo-atrial shunting, but in one of the cases, the diagnosis was made from the check X-ray taken on the day a shunt was introduced. The influence of vincristine sulphate and cyclophosphamide on the radiological appearances and management of the cases has been described. After the diagnosis of skeletal involvement was made three of the children survived over a year with cytotoxic drug treatment; the other case did not respond satisfactory and died from widely disseminated metastases of the central nervous system, 4 months after starting treatment.", "contents": "Diagnosis and management of skeletal metastases from cerebellar medulloblastoma. Four cases of cerebellar medulloblastoma with skeletal metastases have been described. Extracranial metastases from this tumour are extremely rare but the skeleton is the site most commonly involved. The metastases did not occur after ventriculo-atrial shunting, but in one of the cases, the diagnosis was made from the check X-ray taken on the day a shunt was introduced. The influence of vincristine sulphate and cyclophosphamide on the radiological appearances and management of the cases has been described. After the diagnosis of skeletal involvement was made three of the children survived over a year with cytotoxic drug treatment; the other case did not respond satisfactory and died from widely disseminated metastases of the central nervous system, 4 months after starting treatment."} {"id": "PMID:1277953", "title": "Computerised axial tomography. Particular applications and advantages in paediatric neurosurgery.", "content": "The first year's experience of computerised axial tomography (the EMI scanner) in a department of neurosurgery is described, and those features of particular importance in the younger age group are emphasised.", "contents": "Computerised axial tomography. Particular applications and advantages in paediatric neurosurgery. The first year's experience of computerised axial tomography (the EMI scanner) in a department of neurosurgery is described, and those features of particular importance in the younger age group are emphasised."} {"id": "PMID:1277954", "title": "Midline commissurotomy for the treatment of some cases of intractable epilepsy. Preliminary report.", "content": "When epilepsy is localized, limited excisions can be very effective for control of seizures without increased neurological deficit. Van Wagenen found that a seizure discharge confined to one hemosphere would not produce an unconscious state, so he treated his patients with partial or complete sections of the corpus callosum with more success with complete sectioning. Erickson showed that total callosal section was necessary to stop the spread of cortically induced seizures from one hemisphere to the other. Luessenhop reported on four patients treated by divisions of the corpus callosum. Midline commissurotomy is an effective operation for the control of major seizures when the seizure discharge begins in the cortex of one hemisphere and becomes generalized. The procedure is equally applicable to patients with or without major neurological deficit.", "contents": "Midline commissurotomy for the treatment of some cases of intractable epilepsy. Preliminary report. When epilepsy is localized, limited excisions can be very effective for control of seizures without increased neurological deficit. Van Wagenen found that a seizure discharge confined to one hemosphere would not produce an unconscious state, so he treated his patients with partial or complete sections of the corpus callosum with more success with complete sectioning. Erickson showed that total callosal section was necessary to stop the spread of cortically induced seizures from one hemisphere to the other. Luessenhop reported on four patients treated by divisions of the corpus callosum. Midline commissurotomy is an effective operation for the control of major seizures when the seizure discharge begins in the cortex of one hemisphere and becomes generalized. The procedure is equally applicable to patients with or without major neurological deficit."} {"id": "PMID:1277955", "title": "Intracranial pressure monitoring in Reye's syndrome.", "content": "Reye's syndrome is difined as fatty degeneration of the viscera with encephalopathy. The signs are change in consciousness after recovery of a viral illness, vomiting, high fever, and progresseve deterioration of the level of consciousness. Signs of brain stem involvement quickly follow. The clinical findings are: mild elevations of serum transaminases (SGOT and SGPT), normal to slightly elevated bilirubin, abnormal blood-clotting functions, normal to low blood glucose, high blood ammonia, and normal cerebrospinal fluid which may be under increased pressure. Death is due to increased intracranial pressure. Therapy is used to stabilize these signs. It includes: infusion of hypertonic glucose followed by insulin, peritoneal dialysis, and exchange transfusion. Intracranial pressure was monitored continually to determine when therapy should be administered.", "contents": "Intracranial pressure monitoring in Reye's syndrome. Reye's syndrome is difined as fatty degeneration of the viscera with encephalopathy. The signs are change in consciousness after recovery of a viral illness, vomiting, high fever, and progresseve deterioration of the level of consciousness. Signs of brain stem involvement quickly follow. The clinical findings are: mild elevations of serum transaminases (SGOT and SGPT), normal to slightly elevated bilirubin, abnormal blood-clotting functions, normal to low blood glucose, high blood ammonia, and normal cerebrospinal fluid which may be under increased pressure. Death is due to increased intracranial pressure. Therapy is used to stabilize these signs. It includes: infusion of hypertonic glucose followed by insulin, peritoneal dialysis, and exchange transfusion. Intracranial pressure was monitored continually to determine when therapy should be administered."} {"id": "PMID:1277956", "title": "Pinealoma in children.", "content": "The author has a high incidence of pinealoma in his series of intracranial neoplasms. In order to make a diagnosis of pinealoma of the pineal region and of the chiasmal region, pneumoencephalography or ventriculography is very useful in addition to the neurological findings and the plain radiographic findings. The author emphasizes the usefulness of the Millipore filter-cell culture of the cerebrospinal fluid and of the ventriculofiberscopy for the diagnosis of pinealomas in children. The reported cases were treated by a combination of radiation and surgery.", "contents": "Pinealoma in children. The author has a high incidence of pinealoma in his series of intracranial neoplasms. In order to make a diagnosis of pinealoma of the pineal region and of the chiasmal region, pneumoencephalography or ventriculography is very useful in addition to the neurological findings and the plain radiographic findings. The author emphasizes the usefulness of the Millipore filter-cell culture of the cerebrospinal fluid and of the ventriculofiberscopy for the diagnosis of pinealomas in children. The reported cases were treated by a combination of radiation and surgery."} {"id": "PMID:1277957", "title": "Development of a liposarcoma out of the capsules of a hygroma.", "content": "We treated a patient who had a very rare finding: the development of a malignoma out of the capsules of the subdural hygroma covering the right occipitotemporal brain. Lumbar encephalography and arteriography confirmed the fact that surgery was necessary. A subdural-auricular shunt was performed and revised 2 years later. During the second operation, the external and internal capsules were removed in addition to the shunt. 3 years later the hygroma and large capsules were removed again and a ventricular-subdural drainage performed. 1 year later once more a subdural-auricular shunt was performed. 10 months later a tumour was found to be a pseudomucinous liposarcoma with large hyperchromatic nuclei and oval cells with large vacuoles of neutral fat. Renewed growth of the tumour led to the child's death. The histological and macroscopic findings of the capsules suggest the development of a malignoma within the last 3 years.", "contents": "Development of a liposarcoma out of the capsules of a hygroma. We treated a patient who had a very rare finding: the development of a malignoma out of the capsules of the subdural hygroma covering the right occipitotemporal brain. Lumbar encephalography and arteriography confirmed the fact that surgery was necessary. A subdural-auricular shunt was performed and revised 2 years later. During the second operation, the external and internal capsules were removed in addition to the shunt. 3 years later the hygroma and large capsules were removed again and a ventricular-subdural drainage performed. 1 year later once more a subdural-auricular shunt was performed. 10 months later a tumour was found to be a pseudomucinous liposarcoma with large hyperchromatic nuclei and oval cells with large vacuoles of neutral fat. Renewed growth of the tumour led to the child's death. The histological and macroscopic findings of the capsules suggest the development of a malignoma within the last 3 years."} {"id": "PMID:1277958", "title": "Transient loss of recent memory following deep midline cerebral operations.", "content": "We have drawn attention to a post-operative complication of deep midline cerebral operations where operative manipulation occurs to structures associated with memory mechanisms. In the cases presented, the deficit was not permanent probably because the lesions were unilateral, or in conduction pathways.", "contents": "Transient loss of recent memory following deep midline cerebral operations. We have drawn attention to a post-operative complication of deep midline cerebral operations where operative manipulation occurs to structures associated with memory mechanisms. In the cases presented, the deficit was not permanent probably because the lesions were unilateral, or in conduction pathways."} {"id": "PMID:1277960", "title": "[Clinical aspects and diagnosis of the occlusion of upper mesenteric arteries].", "content": "Acute mesenteric vascular occlusion is associated with an extremely high mortality. Only the early diagnosis may be helpful in this condition. A directed anamnesis and close observation of clinical signs and symptoms associated with metabolic acidosis, significant base deficit, elevated white blood count, and arteriography could shorten the time period between vascular occlusion and operation. This is the way, which possibly leads to more gratifying results.", "contents": "[Clinical aspects and diagnosis of the occlusion of upper mesenteric arteries]. Acute mesenteric vascular occlusion is associated with an extremely high mortality. Only the early diagnosis may be helpful in this condition. A directed anamnesis and close observation of clinical signs and symptoms associated with metabolic acidosis, significant base deficit, elevated white blood count, and arteriography could shorten the time period between vascular occlusion and operation. This is the way, which possibly leads to more gratifying results."} {"id": "PMID:1277961", "title": "[Diffuse, nodular-polypous lipomatosis of the small intestine].", "content": "One case of diffuse nodular lipomatosis of the small intestine is reported. Four other cases from the literature are revied. Symptomes and signs, diagnosis and differential diagnosis, as well as surgical treament, are discussed.", "contents": "[Diffuse, nodular-polypous lipomatosis of the small intestine]. One case of diffuse nodular lipomatosis of the small intestine is reported. Four other cases from the literature are revied. Symptomes and signs, diagnosis and differential diagnosis, as well as surgical treament, are discussed."} {"id": "PMID:1277962", "title": "[Cryosurgical treatment of tumors].", "content": "In 84 out of 164 carcinoma patients, admitted from June 1974 to September 1975 -- altogether 98 cryosurgical operations were performed according to the stage of the tumors. This was done as additional treatment to radical operation, as monotherapy, as additional treatment to palliative resection, or as a mono-palliative-therapy. After a discussion of the method, and a critical evaluation of the advantages and disadvantages (including new application areas) cryosurgery is proved to be superior to the conventional method in the destruction of tumor, e.g. in the liver, pancreas, roof of mesentery, and iliac region. The same is true when it is used as a palliative treatment in processes where access is difficult. On the other hand it seems that tumor-freezing shortens the life of patients, weakened through inanition.", "contents": "[Cryosurgical treatment of tumors]. In 84 out of 164 carcinoma patients, admitted from June 1974 to September 1975 -- altogether 98 cryosurgical operations were performed according to the stage of the tumors. This was done as additional treatment to radical operation, as monotherapy, as additional treatment to palliative resection, or as a mono-palliative-therapy. After a discussion of the method, and a critical evaluation of the advantages and disadvantages (including new application areas) cryosurgery is proved to be superior to the conventional method in the destruction of tumor, e.g. in the liver, pancreas, roof of mesentery, and iliac region. The same is true when it is used as a palliative treatment in processes where access is difficult. On the other hand it seems that tumor-freezing shortens the life of patients, weakened through inanition."} {"id": "PMID:1277963", "title": "[Results of spincteromyotomy in anal-spincter achalasia. Histology and postoperative continence].", "content": "Electromanometric studies were performed in a serie of 149 chronically constipated children. One third of the cases showed manometrically an organic and spincter achalasia. In the other two thirds the constipation was functional or psychogenic. In 73 patients a sphincter myotomy was performed. In 50 of these cases the histology of the internal anal sphincter taken by biopsy revealed a close relationship to the electromanometric results. Patients electromanometrically diagnosed at having an organic cause of the achalasia showed histologically in all except one, severe chronic inflammation, fibrosis, hyperplasia of the smooth muscle, or an absence of the ganglion cells in the upper part of the sphincter muscle. In 17 cases with a functional or psychogenic cause only one showed histopathologic findings. Of the 73 patients who were operated upon, 66 had excellent results. In 7 cases encopresis and constipation persisted. The reasons for this are discussed. Pre- and postoperative electromanometric measurements were performed in 30 children, postoperative measurements alone in 59 others. The most important electromanometrically criteria in evaluating the results of the sphincteromyotomy are normalisation of the anorectal pressure profile and the return of regular anorectal fluctuations. Signs of incontinence could not be observed.", "contents": "[Results of spincteromyotomy in anal-spincter achalasia. Histology and postoperative continence]. Electromanometric studies were performed in a serie of 149 chronically constipated children. One third of the cases showed manometrically an organic and spincter achalasia. In the other two thirds the constipation was functional or psychogenic. In 73 patients a sphincter myotomy was performed. In 50 of these cases the histology of the internal anal sphincter taken by biopsy revealed a close relationship to the electromanometric results. Patients electromanometrically diagnosed at having an organic cause of the achalasia showed histologically in all except one, severe chronic inflammation, fibrosis, hyperplasia of the smooth muscle, or an absence of the ganglion cells in the upper part of the sphincter muscle. In 17 cases with a functional or psychogenic cause only one showed histopathologic findings. Of the 73 patients who were operated upon, 66 had excellent results. In 7 cases encopresis and constipation persisted. The reasons for this are discussed. Pre- and postoperative electromanometric measurements were performed in 30 children, postoperative measurements alone in 59 others. The most important electromanometrically criteria in evaluating the results of the sphincteromyotomy are normalisation of the anorectal pressure profile and the return of regular anorectal fluctuations. Signs of incontinence could not be observed."} {"id": "PMID:1277965", "title": "Chronobiology in 1975.", "content": "A spectrum of rhythms with several frequencies importantly characterizes not only the central nervous system but also the neuroendocrines and endocrines, other structures and organs, beyond the level of the cell to subcellular structures; it has a wide bearing since chronobiologic methods and facts relate to both basic research and its bearing on major problems of our day. Perhaps most important, computer analysis of data series allows study of temporal structure, progressive and rhythmic variations in life processes and in their responses to environment and drugs. By such methods coupled to modern data collection and/or self-measurement, chronobiology is particularly promising in the following areas, cited as illustrative rather than comprehensive examples: 1. Work hygiene: optimization of work schedules by adjustment of regular schedules and in particular of shift-work to the individuals' physical and mental rhythms. Experimentally, differences in manner of schedule change can account for the difference between the life span shortening and lengthening. 2. Population control: improved methods for detecting the neural as well as neurohormonal regulation of ovulatory cycles should aid efficient family planning by the recognition of a spectrum of rhythms and its synchronization with socio-ecologic factors acting, perhaps, via olfactory and/or other sensory modalities; 3. Nutrition: optimizing the utilization of ever scarcer food supplies and also the benefit from both oral and parenteral medications by meal timing; 4. Education: providing a do-it-yourself system for monitoring individual health in the context of secondary and adult education and as the basis for preventive health care; and, in another context, taking individual mental rhythms as well as morningness-eveningness into account in teaching and learning; 5. Health care: Any risk, e.g., from blood pressure rhythm alteration (perhaps preceding by years intermittent labile elevation) will be detected earlier and more efficiently by multiple measurements readily obtained by autorhythmometry. Results of such an endeavor provide at any one time indices that can be compared with an individualized rhythmometric reference standard as well as peer group rhythm parameters. The rhythm-determined average is more reliable than the single measurement. Other individualized characteristics of a rhythm, such as measures of extent of change or timing of change, may constitute an early warning signal and could be monitored by self-measured or preferably automatically-collected data. Timely and timed treatment can then be sought to prevent, in the case of blood pressure, elevation and consequent debilitating disease such as coronary infarction and stroke. 6. One can strive toward the more specific correction of any pathogenic rhythm alteration when such can be recognized by modern methods of data collection and data analysis...", "contents": "Chronobiology in 1975. A spectrum of rhythms with several frequencies importantly characterizes not only the central nervous system but also the neuroendocrines and endocrines, other structures and organs, beyond the level of the cell to subcellular structures; it has a wide bearing since chronobiologic methods and facts relate to both basic research and its bearing on major problems of our day. Perhaps most important, computer analysis of data series allows study of temporal structure, progressive and rhythmic variations in life processes and in their responses to environment and drugs. By such methods coupled to modern data collection and/or self-measurement, chronobiology is particularly promising in the following areas, cited as illustrative rather than comprehensive examples: 1. Work hygiene: optimization of work schedules by adjustment of regular schedules and in particular of shift-work to the individuals' physical and mental rhythms. Experimentally, differences in manner of schedule change can account for the difference between the life span shortening and lengthening. 2. Population control: improved methods for detecting the neural as well as neurohormonal regulation of ovulatory cycles should aid efficient family planning by the recognition of a spectrum of rhythms and its synchronization with socio-ecologic factors acting, perhaps, via olfactory and/or other sensory modalities; 3. Nutrition: optimizing the utilization of ever scarcer food supplies and also the benefit from both oral and parenteral medications by meal timing; 4. Education: providing a do-it-yourself system for monitoring individual health in the context of secondary and adult education and as the basis for preventive health care; and, in another context, taking individual mental rhythms as well as morningness-eveningness into account in teaching and learning; 5. Health care: Any risk, e.g., from blood pressure rhythm alteration (perhaps preceding by years intermittent labile elevation) will be detected earlier and more efficiently by multiple measurements readily obtained by autorhythmometry. Results of such an endeavor provide at any one time indices that can be compared with an individualized rhythmometric reference standard as well as peer group rhythm parameters. The rhythm-determined average is more reliable than the single measurement. Other individualized characteristics of a rhythm, such as measures of extent of change or timing of change, may constitute an early warning signal and could be monitored by self-measured or preferably automatically-collected data. Timely and timed treatment can then be sought to prevent, in the case of blood pressure, elevation and consequent debilitating disease such as coronary infarction and stroke. 6. One can strive toward the more specific correction of any pathogenic rhythm alteration when such can be recognized by modern methods of data collection and data analysis..."} {"id": "PMID:1277966", "title": "Chronobiologic and inbred strain differences in blood hemoglobin of the mouse.", "content": "Hemoglobin concentration in mouse blood exhibits differences as a function of inbred strain, age and circadian rhythm. The detection of an age-effect can depend upon the circadian stage chosen for sampling.", "contents": "Chronobiologic and inbred strain differences in blood hemoglobin of the mouse. Hemoglobin concentration in mouse blood exhibits differences as a function of inbred strain, age and circadian rhythm. The detection of an age-effect can depend upon the circadian stage chosen for sampling."} {"id": "PMID:1277967", "title": "Effect of fasting on the circadian rhythm of serum insulin levels.", "content": "The effects of 29 hrs of fast on gastric content, serum glucose and IRI levels were studied twice in normal mice. Both experiments showed a circadian rhythm of all parameters studied in control animals. Fasting in both experiments was unable to modify the circadian rhythm of gastric content and serum glucose levels, in spite of substantial modifications in their absolute values. Conversely, while the rhythm of serum IRI levels was not changed in one experiment, the other showed a variation with no level of significance. The latter coincides with the greatest decrease of both gastric content and serum glucose levels. Therefore, circadian IRI levels should be only within some range under the control of food intake. This suggests the possible existence of a threshold for absolute glucose and/or gastric content variation under which serum IRI level rhythm is unable to reach the level of significance.", "contents": "Effect of fasting on the circadian rhythm of serum insulin levels. The effects of 29 hrs of fast on gastric content, serum glucose and IRI levels were studied twice in normal mice. Both experiments showed a circadian rhythm of all parameters studied in control animals. Fasting in both experiments was unable to modify the circadian rhythm of gastric content and serum glucose levels, in spite of substantial modifications in their absolute values. Conversely, while the rhythm of serum IRI levels was not changed in one experiment, the other showed a variation with no level of significance. The latter coincides with the greatest decrease of both gastric content and serum glucose levels. Therefore, circadian IRI levels should be only within some range under the control of food intake. This suggests the possible existence of a threshold for absolute glucose and/or gastric content variation under which serum IRI level rhythm is unable to reach the level of significance."} {"id": "PMID:1277968", "title": "The 24-h pattern of human prolactin in serum.", "content": "Radioimmunoassay determinations of serum prolactin every 2 hrs in twelve healthy subjects (six women and six men), aged between 22 and 34, reveal that several episodes of hormone secretion occur over a 24-h period. The two episodes displaying significant oscillations have 24-h and 8-h periods, with maxima occurring respectively at 04(30) and at 07(00), 15(00) and 23(00). Accordingly, the highest prolactin levels in serum occur during the night, but oscillations are present throughout the day. The observation schedule adopted leads us to conclude that the main secretory rhythm is synchronized with sleep. The 8-h periods seem to be rather dependent on the course of time.", "contents": "The 24-h pattern of human prolactin in serum. Radioimmunoassay determinations of serum prolactin every 2 hrs in twelve healthy subjects (six women and six men), aged between 22 and 34, reveal that several episodes of hormone secretion occur over a 24-h period. The two episodes displaying significant oscillations have 24-h and 8-h periods, with maxima occurring respectively at 04(30) and at 07(00), 15(00) and 23(00). Accordingly, the highest prolactin levels in serum occur during the night, but oscillations are present throughout the day. The observation schedule adopted leads us to conclude that the main secretory rhythm is synchronized with sleep. The 8-h periods seem to be rather dependent on the course of time."} {"id": "PMID:1277969", "title": "Circadian rhythms in blood, urine and gastric acid secretion of presumably healthy volunteers.", "content": "The mean conisor technique reveals statistically significant circadian rhythms for serum concentrations of iron, chloride, cortisol, PBI, the fibrinolytic activity of blood, urinary iron excretion and gastric acid secretion in studies covering a 24-h span for presumably healthy subjects. Quantification of these rhythms provides internationally comparable reference values both for the conventional clinical laboratory and for any special chronobiologic applications.", "contents": "Circadian rhythms in blood, urine and gastric acid secretion of presumably healthy volunteers. The mean conisor technique reveals statistically significant circadian rhythms for serum concentrations of iron, chloride, cortisol, PBI, the fibrinolytic activity of blood, urinary iron excretion and gastric acid secretion in studies covering a 24-h span for presumably healthy subjects. Quantification of these rhythms provides internationally comparable reference values both for the conventional clinical laboratory and for any special chronobiologic applications."} {"id": "PMID:1277974", "title": "Volvulus of the colon--a continuing surgical problem.", "content": "Twenty-six cases of colonic volvulus from the University of Kentucky Medical Center and the Lexington Veterans Administration Hospital, covering a ten-year period, are presented. Overall mortality was 19 per cent (5 of 26 patients). Cecal volvulus carried the greatest mortality, 30 per cent (3 of 10 patients), whereas sigmoidal volvulus had relatively low mortality rate of 7 per cent (1 or 15). A single patient who had volvulus of the transverse colon died. The most significant factor leading to death was not necrotic bowel but the necessity for emergency operation in these generally debilitated patients. A plan of management with the major aim to convert emergency situations into elective or urgent ones is presented with the expectation that the mortality rate can be improved.", "contents": "Volvulus of the colon--a continuing surgical problem. Twenty-six cases of colonic volvulus from the University of Kentucky Medical Center and the Lexington Veterans Administration Hospital, covering a ten-year period, are presented. Overall mortality was 19 per cent (5 of 26 patients). Cecal volvulus carried the greatest mortality, 30 per cent (3 of 10 patients), whereas sigmoidal volvulus had relatively low mortality rate of 7 per cent (1 or 15). A single patient who had volvulus of the transverse colon died. The most significant factor leading to death was not necrotic bowel but the necessity for emergency operation in these generally debilitated patients. A plan of management with the major aim to convert emergency situations into elective or urgent ones is presented with the expectation that the mortality rate can be improved."} {"id": "PMID:1277975", "title": "Intraoperative Chaffin sump recto-colonic irrigation.", "content": "A simple method for intraoperative rectocolonic irrigation using the time-honored Chaffin sump drain is recommended. It assures an empty particulate matter-free bowel for anastomosis, washes out malignant cells, and provides proof of the integrity of anastomosis and decompression of the proximal bowel when indicated.", "contents": "Intraoperative Chaffin sump recto-colonic irrigation. A simple method for intraoperative rectocolonic irrigation using the time-honored Chaffin sump drain is recommended. It assures an empty particulate matter-free bowel for anastomosis, washes out malignant cells, and provides proof of the integrity of anastomosis and decompression of the proximal bowel when indicated."} {"id": "PMID:1277976", "title": "Management of focally malignant pedunculated adenomatous colorectal polyps.", "content": "A hospital record review identified 59 patients whose sole colorectal pathology was a pedunculated, adenomatous polyp with a focus of malignancy confined to the head of the tumor. Thirty-one patients had polyps with in-situ carcinoma, and 28 patients had foci of invasive carcinoma. Sixteen patients who had lesions in situ underwent laparotomy, and not a single instance of metastasis was found. Twenty patients who had carcinoma in situ received only local treatment, and 15 are alive and well. None of the patients treated locally has developed subsequent colorectal cancer, and 12 have survived at least five years following treatment. Of the 28 patients who had invasive carcinoma confined to the head of an adenoma, 19 are alive and well, and 17 have lived five years or more following treatment. There was one instance of lymph-node metastasis, which occurred in a patient who had a malignant lesion extending to the neck of the tumor and tumor cells in the lymphatics in the head of the polyp. All of the eight patients treated locally are alive and well, and five have lived at least five years following treatment. The results of this study, coupled with the rarity of reported metastasis from focally malignant, pedunculated, adenomatous colorectal polyps, strongly suggest that local treatment is sufficient for the vast majority of these lesions. Evidence from the literature suggests that resective therapy should be considered when 1) lymphatics within the head of the polyp contain tumor cells; 2) the cancer is highly undifferentiated; 3) the pedicle is extremely short and malignant changes extend to the neck of the adenoma.", "contents": "Management of focally malignant pedunculated adenomatous colorectal polyps. A hospital record review identified 59 patients whose sole colorectal pathology was a pedunculated, adenomatous polyp with a focus of malignancy confined to the head of the tumor. Thirty-one patients had polyps with in-situ carcinoma, and 28 patients had foci of invasive carcinoma. Sixteen patients who had lesions in situ underwent laparotomy, and not a single instance of metastasis was found. Twenty patients who had carcinoma in situ received only local treatment, and 15 are alive and well. None of the patients treated locally has developed subsequent colorectal cancer, and 12 have survived at least five years following treatment. Of the 28 patients who had invasive carcinoma confined to the head of an adenoma, 19 are alive and well, and 17 have lived five years or more following treatment. There was one instance of lymph-node metastasis, which occurred in a patient who had a malignant lesion extending to the neck of the tumor and tumor cells in the lymphatics in the head of the polyp. All of the eight patients treated locally are alive and well, and five have lived at least five years following treatment. The results of this study, coupled with the rarity of reported metastasis from focally malignant, pedunculated, adenomatous colorectal polyps, strongly suggest that local treatment is sufficient for the vast majority of these lesions. Evidence from the literature suggests that resective therapy should be considered when 1) lymphatics within the head of the polyp contain tumor cells; 2) the cancer is highly undifferentiated; 3) the pedicle is extremely short and malignant changes extend to the neck of the adenoma."} {"id": "PMID:1277977", "title": "A comparison of the results of extraperitoneal and intraperitoneal techniques for construction of terminal iliac colostomies.", "content": "In a series of 251 patients followed for at least two years after abdominoperineal excision for carcinoma of the rectum, those given extraperitoneal iliac colostomies were found to have significantly lower incidences of pericolostomy herniation, prolapse, and recession than those given intraperitoneal colostomies. There was no difference between the frequencies of mechanical intestinal obstruction.", "contents": "A comparison of the results of extraperitoneal and intraperitoneal techniques for construction of terminal iliac colostomies. In a series of 251 patients followed for at least two years after abdominoperineal excision for carcinoma of the rectum, those given extraperitoneal iliac colostomies were found to have significantly lower incidences of pericolostomy herniation, prolapse, and recession than those given intraperitoneal colostomies. There was no difference between the frequencies of mechanical intestinal obstruction."} {"id": "PMID:1277978", "title": "The pathology of the appendix in ulcerative colitis.", "content": "Sixty-five patients who had the documented histologic diagnosis of chronic ulcerative colitis were selected in order to study appendiceal involvement in this disease. There were 28 males and 37 female patients with an average age of 30 years. The incidence of appendiceal involvement involving the right colon was found to be 47 per cent. In all of these cases the appendiceal involvement occurred in association with the disease process in the cecum or the right colon. In seven patients a classic picture of ulcerative appendicitis in active phase was found. In 78 per cent of patients a similarity between the disease stages in the colon and in the appendix was observed.", "contents": "The pathology of the appendix in ulcerative colitis. Sixty-five patients who had the documented histologic diagnosis of chronic ulcerative colitis were selected in order to study appendiceal involvement in this disease. There were 28 males and 37 female patients with an average age of 30 years. The incidence of appendiceal involvement involving the right colon was found to be 47 per cent. In all of these cases the appendiceal involvement occurred in association with the disease process in the cecum or the right colon. In seven patients a classic picture of ulcerative appendicitis in active phase was found. In 78 per cent of patients a similarity between the disease stages in the colon and in the appendix was observed."} {"id": "PMID:1277982", "title": "Motor neuron disease: retrospective study of associated abnormalities.", "content": "In a retrospective study of the charts of 39 patients who had motor neuron disease we found that over 50 percent of patients had radiographic abnormalities of bone and over 20 percent had serum calcium concentrations out of the range observed in normal controls. Statistical analysis indicated that, in respect to serum calcium levels, patients who have motor neuron disease are a separate population. These findings, which might reflect a disturbance in bone or calcium metabolism in patients with motor neuron disease, are of interest in view of the known ability of divalent ions other than calcium, such as lead and mercury, to simulate motor neuron disease, and the discovery that patients with proven primary and secondary hyperparathyroidism may have features of amyotrophic lateral sclerosis.", "contents": "Motor neuron disease: retrospective study of associated abnormalities. In a retrospective study of the charts of 39 patients who had motor neuron disease we found that over 50 percent of patients had radiographic abnormalities of bone and over 20 percent had serum calcium concentrations out of the range observed in normal controls. Statistical analysis indicated that, in respect to serum calcium levels, patients who have motor neuron disease are a separate population. These findings, which might reflect a disturbance in bone or calcium metabolism in patients with motor neuron disease, are of interest in view of the known ability of divalent ions other than calcium, such as lead and mercury, to simulate motor neuron disease, and the discovery that patients with proven primary and secondary hyperparathyroidism may have features of amyotrophic lateral sclerosis."} {"id": "PMID:1277983", "title": "Intravenous chlorimipramine and depressive subtypes.", "content": "An open clinical trial with intravenous chlorimipramine was carried out on twenty depressed inpatients, diagnosed as primary or secondary affective disorders following a classificatory scheme for use in psychiatric research. Eleven of twelve patients with primary affective disorders had a significant decrease in symptoms of depression at the end of two weeks. In contrast, eight patients with secondary affective disorders did not show such significant improvement. Changes in physiological parameters (systolic blood pressure) were significantly greater in the primary affective disorders than in the secondary ones. It is inferred from the results of this trial, that intravenous administration of chlorimipramine is a safe and feasible procedure, which may compare to electroconvulsive therapy in the treatment of severe unipolar and bipolar depressions.", "contents": "Intravenous chlorimipramine and depressive subtypes. An open clinical trial with intravenous chlorimipramine was carried out on twenty depressed inpatients, diagnosed as primary or secondary affective disorders following a classificatory scheme for use in psychiatric research. Eleven of twelve patients with primary affective disorders had a significant decrease in symptoms of depression at the end of two weeks. In contrast, eight patients with secondary affective disorders did not show such significant improvement. Changes in physiological parameters (systolic blood pressure) were significantly greater in the primary affective disorders than in the secondary ones. It is inferred from the results of this trial, that intravenous administration of chlorimipramine is a safe and feasible procedure, which may compare to electroconvulsive therapy in the treatment of severe unipolar and bipolar depressions."} {"id": "PMID:1277984", "title": "Ballistic movements of the arm in systemic lupus erythematosis.", "content": "The case of a 24-year old woman with systemic lupus erythematosis and central nervous system disease manifested by ballistic movements of the left arm is presented. She also had bilateral cerebral infarcts with pseudobulbar palsy. Ballismus is not generally known to be a manifestation of systemic lupus although there have been been reports of chorea in this disease which has responded to treatment with corticosteroids. In the present case, the ballismus disappeared when very large doses of steroids were given. This suggests that massive doses of corticosteroids may be needed for effective treatment of central nervous system lupus.", "contents": "Ballistic movements of the arm in systemic lupus erythematosis. The case of a 24-year old woman with systemic lupus erythematosis and central nervous system disease manifested by ballistic movements of the left arm is presented. She also had bilateral cerebral infarcts with pseudobulbar palsy. Ballismus is not generally known to be a manifestation of systemic lupus although there have been been reports of chorea in this disease which has responded to treatment with corticosteroids. In the present case, the ballismus disappeared when very large doses of steroids were given. This suggests that massive doses of corticosteroids may be needed for effective treatment of central nervous system lupus."} {"id": "PMID:1277980", "title": "Deviation of the rectosigmoid colon simulating a presacral tumor: report of a case.", "content": "The rectosigmoid colon has a potential for a great deal of mobility and variation of position. This is partially due to the wide variation in length and distal attachment of the sigmoid mesocolon. When anterior or lateral deviations of the distal sigmoid and rectum are found on barium-enema examinations, the possibility of anomalous fixation of the rectosigmoid should be considered.", "contents": "Deviation of the rectosigmoid colon simulating a presacral tumor: report of a case. The rectosigmoid colon has a potential for a great deal of mobility and variation of position. This is partially due to the wide variation in length and distal attachment of the sigmoid mesocolon. When anterior or lateral deviations of the distal sigmoid and rectum are found on barium-enema examinations, the possibility of anomalous fixation of the rectosigmoid should be considered."} {"id": "PMID:1277985", "title": "Further examination of a biochemical test for suicide potential.", "content": "The use of biological data, especially adrenal cortical activity, to enhance the assessment of suicide potential has been suggested and briefly argued in the literature. In this report data is presented on two suicide patients. One patient suicided 8 months after her 4-month hospitalization during which time her 17-hydroxycorticosteroid (17-OHCS) excretion remained at low levels. The second patient suicided on his thirteenth hospital day; his 17-OHCS excretion was moderately elevated, but consistent with his high anxiety and depression ratings. One case is used to support the previous findings that low 17-OHCS affords the clinician no reassurance regarding suicidal risk in the future. The other case illustrates the difficulty in interpreting moderate elevation in arousal sensitive endocrine systems in light of clinically manifest anxiety and/or depression.", "contents": "Further examination of a biochemical test for suicide potential. The use of biological data, especially adrenal cortical activity, to enhance the assessment of suicide potential has been suggested and briefly argued in the literature. In this report data is presented on two suicide patients. One patient suicided 8 months after her 4-month hospitalization during which time her 17-hydroxycorticosteroid (17-OHCS) excretion remained at low levels. The second patient suicided on his thirteenth hospital day; his 17-OHCS excretion was moderately elevated, but consistent with his high anxiety and depression ratings. One case is used to support the previous findings that low 17-OHCS affords the clinician no reassurance regarding suicidal risk in the future. The other case illustrates the difficulty in interpreting moderate elevation in arousal sensitive endocrine systems in light of clinically manifest anxiety and/or depression."} {"id": "PMID:1277986", "title": "New developments in electroconvulsive therapy.", "content": "Recent legal limitations on the availability of electroconvulsive therapy (ECT) are discussed in relation to the constitutional rights of the doctor-patient relationship. Technical factors which may contribute to the debate about ECT are presented. Improved methods of administration and documentation are proposed.", "contents": "New developments in electroconvulsive therapy. Recent legal limitations on the availability of electroconvulsive therapy (ECT) are discussed in relation to the constitutional rights of the doctor-patient relationship. Technical factors which may contribute to the debate about ECT are presented. Improved methods of administration and documentation are proposed."} {"id": "PMID:1277987", "title": "Hyperpyrexia in catatonic states.", "content": "A patient with an underlying brain disease and catatonia associated with fever of unknown origin, who responded to ECT is presented. The role of dopamine in the basal ganglia in the etiology of catatonic states and its possible relationship to the symptomatology of the patient and his response to ECT is discussed.", "contents": "Hyperpyrexia in catatonic states. A patient with an underlying brain disease and catatonia associated with fever of unknown origin, who responded to ECT is presented. The role of dopamine in the basal ganglia in the etiology of catatonic states and its possible relationship to the symptomatology of the patient and his response to ECT is discussed."} {"id": "PMID:1278006", "title": "[Investigations into urea elimination in patients with advanced chronic renal failure during forced diuresis].", "content": "Controlled balance studies were performed in 12 oedema-free patients with advanced chronic renal failure with optimal dietary pretreatment. Forced water diuresis did not result in a significantly increased urea excretion as compared with spontaneous diuresis. Furosemide diuresis resulted in a significant increase (P less than 0.05) which was irrelevant therapeutically. The serum urea may even increase slightly under furosemide due to massive fluid loss. During thirst-regulated diuresis of advanced chronic renal failure urea back-diffusion is probably already reduced to a minimum. Normal hydration provided, forced water diuresis (oral or parenteral fluid) is useless and irresponsible as it poses additional risks in such patients. Furosemide in high dosage in over-hydrated patients is an effective diuretic even in advanced renal failure. The slightly significant increase in urea excretion during furosemide treatment does not result in important benefits in dietetically well treated patients.", "contents": "[Investigations into urea elimination in patients with advanced chronic renal failure during forced diuresis]. Controlled balance studies were performed in 12 oedema-free patients with advanced chronic renal failure with optimal dietary pretreatment. Forced water diuresis did not result in a significantly increased urea excretion as compared with spontaneous diuresis. Furosemide diuresis resulted in a significant increase (P less than 0.05) which was irrelevant therapeutically. The serum urea may even increase slightly under furosemide due to massive fluid loss. During thirst-regulated diuresis of advanced chronic renal failure urea back-diffusion is probably already reduced to a minimum. Normal hydration provided, forced water diuresis (oral or parenteral fluid) is useless and irresponsible as it poses additional risks in such patients. Furosemide in high dosage in over-hydrated patients is an effective diuretic even in advanced renal failure. The slightly significant increase in urea excretion during furosemide treatment does not result in important benefits in dietetically well treated patients."} {"id": "PMID:1278007", "title": "[Scanning in progessive pulmonary failure (shock-lung): preliminary results of a clinical study].", "content": "Lung scanning was performed on five patients with shock lung. It gave no evidence of morphological (pre-capillary) arterio-venous shunts or of increased pulmonary arterial pressure. Nor was there evidence of perfusion-ventilation inequality in the scan. The cause of the progressive pulmonary insufficiency was most likely due to maldistribution of gases in the microscopic region and to diffusion abnormalities.", "contents": "[Scanning in progessive pulmonary failure (shock-lung): preliminary results of a clinical study]. Lung scanning was performed on five patients with shock lung. It gave no evidence of morphological (pre-capillary) arterio-venous shunts or of increased pulmonary arterial pressure. Nor was there evidence of perfusion-ventilation inequality in the scan. The cause of the progressive pulmonary insufficiency was most likely due to maldistribution of gases in the microscopic region and to diffusion abnormalities."} {"id": "PMID:1278008", "title": "[Use of muscle aspiration biopsy needle for diagnostic purposes].", "content": "The needle for aspiration biopsy of skeletal muscle, previously developed for biochemical and physiological purposes, has been introduced in the diagnosis of muscular and vascular diseases. Evidence is presented that this needle is a useful tool for routine evaluation of such disorders.", "contents": "[Use of muscle aspiration biopsy needle for diagnostic purposes]. The needle for aspiration biopsy of skeletal muscle, previously developed for biochemical and physiological purposes, has been introduced in the diagnosis of muscular and vascular diseases. Evidence is presented that this needle is a useful tool for routine evaluation of such disorders."} {"id": "PMID:1278014", "title": "[Normal cholesterol and triglyceride levels in serum: comparison of enzymatic and colorimetric methods (author's transl)].", "content": "Three methods were used to determine the normal ranges for cholesterol and triglyceride in serum of 385 blood donors (289 men, 96 women, aged 18-50 years). Enzymatically determined cholesterol levels had an upper normal range to 6.73-6.99 mmol/l (2.6-2.7 g/l), i.e. lower than with the colorimetric method. The upper range for the triglycerides was 2.28-2.85 mmol/l (2.0-2.5 g/l). Both variables were age and sex-dependent. It is suggested that in assessing lipid levels they should be divided into normal, border-line and definitely abnormal values.", "contents": "[Normal cholesterol and triglyceride levels in serum: comparison of enzymatic and colorimetric methods (author's transl)]. Three methods were used to determine the normal ranges for cholesterol and triglyceride in serum of 385 blood donors (289 men, 96 women, aged 18-50 years). Enzymatically determined cholesterol levels had an upper normal range to 6.73-6.99 mmol/l (2.6-2.7 g/l), i.e. lower than with the colorimetric method. The upper range for the triglycerides was 2.28-2.85 mmol/l (2.0-2.5 g/l). Both variables were age and sex-dependent. It is suggested that in assessing lipid levels they should be divided into normal, border-line and definitely abnormal values."} {"id": "PMID:1278023", "title": "[Intragastric titration, a method for clinically testing the effect of antacids].", "content": "Intragastric titration can be used not only for the quantiative assessment of gastric secretion in healthy subjects and patients with peptic ulcer, but also for differentiating disorders in the regulation of HCI secretion. It is useful foe evaluating the effect of antacids after stimulation of acid secretion with a test meal. The duration of action of an antacid taken about one hour after a meal was much greater than when taken on an empty stomach. Results in 12 healthy subjects indicate that frequent small meals (6 to 8 daily) and antacids between meals greatly reduce gastric acidity. Whether these findings hold true for patients with peptic ulcer remains to be determined.", "contents": "[Intragastric titration, a method for clinically testing the effect of antacids]. Intragastric titration can be used not only for the quantiative assessment of gastric secretion in healthy subjects and patients with peptic ulcer, but also for differentiating disorders in the regulation of HCI secretion. It is useful foe evaluating the effect of antacids after stimulation of acid secretion with a test meal. The duration of action of an antacid taken about one hour after a meal was much greater than when taken on an empty stomach. Results in 12 healthy subjects indicate that frequent small meals (6 to 8 daily) and antacids between meals greatly reduce gastric acidity. Whether these findings hold true for patients with peptic ulcer remains to be determined."} {"id": "PMID:1278024", "title": "[Embolic occlusion of the left renal artery with a non-functioning right kidney].", "content": "In a 69-year-old patient with absolute arrhythmia and a rightsided non-functioning kidney embolism occurred in the left renal artery. Despite 2 1/2 days of anuria embolectomy was successful. Fastest possible restoration of renal perfusion is critical for organ preservation.", "contents": "[Embolic occlusion of the left renal artery with a non-functioning right kidney]. In a 69-year-old patient with absolute arrhythmia and a rightsided non-functioning kidney embolism occurred in the left renal artery. Despite 2 1/2 days of anuria embolectomy was successful. Fastest possible restoration of renal perfusion is critical for organ preservation."} {"id": "PMID:1278031", "title": "[Isoenzymes of creatine kinase in extracardiac disease and after various diagnostic and therapeutic procedures].", "content": "Creatine kinase MB isoenzyme was measured (using antibody inhibition) in serum of patients with exogenous intoxication, acute pancreatitis, cerebrovascular accidents, meningitis, encephalitis, skeletal muscle disease, shock, postoperative states and after coronary arteriography, cardiac catherisation of cardioversion. CK-MB activity was revealed only in sera of patients with exogenous intoxication (severity III and IV), polymyositis, scleroderma, after operation or after coronary arteriography, cardiac catherisation or cardioversion. As it is not possible to differentiate between CK-MB and CK-BB using inhibiting antibodies against CK-M subunit, CK-isoenzyme activity was determined in parallel, using precipitating antibodies. No CK-BB was found in any case. The determination of CK-MB isoenzyme after blocking of the CK-MB subunit by means of inhibiting antibodies is suitable for clinical diagnosis. The method significantly increases the value of creatine kinase measurement.", "contents": "[Isoenzymes of creatine kinase in extracardiac disease and after various diagnostic and therapeutic procedures]. Creatine kinase MB isoenzyme was measured (using antibody inhibition) in serum of patients with exogenous intoxication, acute pancreatitis, cerebrovascular accidents, meningitis, encephalitis, skeletal muscle disease, shock, postoperative states and after coronary arteriography, cardiac catherisation of cardioversion. CK-MB activity was revealed only in sera of patients with exogenous intoxication (severity III and IV), polymyositis, scleroderma, after operation or after coronary arteriography, cardiac catherisation or cardioversion. As it is not possible to differentiate between CK-MB and CK-BB using inhibiting antibodies against CK-M subunit, CK-isoenzyme activity was determined in parallel, using precipitating antibodies. No CK-BB was found in any case. The determination of CK-MB isoenzyme after blocking of the CK-MB subunit by means of inhibiting antibodies is suitable for clinical diagnosis. The method significantly increases the value of creatine kinase measurement."} {"id": "PMID:1278032", "title": "[Regional contraction of the left ventricle in congestive cardiomyopathy].", "content": "Regional analysis of ventricular angiograms obtained at diagnostic cardiac investigation was undertaken in 22 patients with congestive cardiomyopathy and 16 healthy subjects. Applying the concept of radial motion, directed towards the centre of the left ventricle, akinetic zones of 20 to 50% of left ventricle circumference were found in more than half the cases of congestive myopathy. The greater the area of regional abnormal motion, the greater the reduction in haemodynamic variables and left ventricular function. The clinical status of nearly all patients with large akinetic areas deteriorated in the subsequent period of observation (6-48 months, averaging 26 months). But in patients without additional abnormal regional wall motion the clinical condition remained stable. A large akinetic area in congestive myopathy indicates severe reduction in left ventricular function and is an unfavourable prognostic sign.", "contents": "[Regional contraction of the left ventricle in congestive cardiomyopathy]. Regional analysis of ventricular angiograms obtained at diagnostic cardiac investigation was undertaken in 22 patients with congestive cardiomyopathy and 16 healthy subjects. Applying the concept of radial motion, directed towards the centre of the left ventricle, akinetic zones of 20 to 50% of left ventricle circumference were found in more than half the cases of congestive myopathy. The greater the area of regional abnormal motion, the greater the reduction in haemodynamic variables and left ventricular function. The clinical status of nearly all patients with large akinetic areas deteriorated in the subsequent period of observation (6-48 months, averaging 26 months). But in patients without additional abnormal regional wall motion the clinical condition remained stable. A large akinetic area in congestive myopathy indicates severe reduction in left ventricular function and is an unfavourable prognostic sign."} {"id": "PMID:1278033", "title": "[Recto-vaginal fistulae: causes, treatment, results (author's transl)].", "content": "Among recto-vaginal fistulae in 41 patients 22 were due to radiotherapy, 6 to inflammatory disease, 4 occurred as a postoperative complication and 9 were carcinomatous fistulous tracts. Passage of stool or air per vaginam is a pathognomonic sign. The fistula can usually be diagnosed by routine gynaecological examination. Barium enema, barium meal with follow-through or colpography often demonstrate the fistula. Except for a few cases in which the fistula closes spontaneously (most frequently those which occur postoperatively), treatment is surgical. Intestinal resection is often necessary in the inflammatory fistulae and those after radiotherapy. In fistulae due to carcinoma colostomy will improve symptoms: radical removal of the tumour is rarely possible. 31 of the 44 women are cured, while in two a fistula has persisted.", "contents": "[Recto-vaginal fistulae: causes, treatment, results (author's transl)]. Among recto-vaginal fistulae in 41 patients 22 were due to radiotherapy, 6 to inflammatory disease, 4 occurred as a postoperative complication and 9 were carcinomatous fistulous tracts. Passage of stool or air per vaginam is a pathognomonic sign. The fistula can usually be diagnosed by routine gynaecological examination. Barium enema, barium meal with follow-through or colpography often demonstrate the fistula. Except for a few cases in which the fistula closes spontaneously (most frequently those which occur postoperatively), treatment is surgical. Intestinal resection is often necessary in the inflammatory fistulae and those after radiotherapy. In fistulae due to carcinoma colostomy will improve symptoms: radical removal of the tumour is rarely possible. 31 of the 44 women are cured, while in two a fistula has persisted."} {"id": "PMID:1278034", "title": "[Pathological perfusion scintigram of the myocardium in angina pectoris patients with normal coronary angiograms (author's transl)].", "content": "In patients aged 24 to 45 years with angina pectoris, pathological changes in the exercise electrocardiogram and a normal coronary angiogram, a disturbance of the pattern of myocardial perfusion could be demonstrated in addition by scintigraphy. The cause of this disturbance of myocardial perfusion is unknown. Myocardial scintigraphy is indicated (1) to demonstrate an otherwise undetectable disturbance in the blood flow of the myocardium with a morphologically normal coronary system, (2) in subtotal coronary stenosis before the decision to perform a coronary bypass operation is made, (3) in cases of anginal syndrome with normal coronary angiograms.", "contents": "[Pathological perfusion scintigram of the myocardium in angina pectoris patients with normal coronary angiograms (author's transl)]. In patients aged 24 to 45 years with angina pectoris, pathological changes in the exercise electrocardiogram and a normal coronary angiogram, a disturbance of the pattern of myocardial perfusion could be demonstrated in addition by scintigraphy. The cause of this disturbance of myocardial perfusion is unknown. Myocardial scintigraphy is indicated (1) to demonstrate an otherwise undetectable disturbance in the blood flow of the myocardium with a morphologically normal coronary system, (2) in subtotal coronary stenosis before the decision to perform a coronary bypass operation is made, (3) in cases of anginal syndrome with normal coronary angiograms."} {"id": "PMID:1278035", "title": "[A new method of demonstrating the regional lymph nodes of the urinary bladder (author's transl)].", "content": "Pedal lymphography as used up to now does not fully demonstrate the lymphatic drainage of the bladder. A new method is presented in which Lipiodol-Ultra-Fluid is injected into the submucosal layer of the bladder wall under endoscopic vision. In 27 endovesical lymphographies the following lymph nodes could be demonstrated: the anterior, lateral and posterior vesical, the obturator, the external and internal iliac and the common iliac nodes.", "contents": "[A new method of demonstrating the regional lymph nodes of the urinary bladder (author's transl)]. Pedal lymphography as used up to now does not fully demonstrate the lymphatic drainage of the bladder. A new method is presented in which Lipiodol-Ultra-Fluid is injected into the submucosal layer of the bladder wall under endoscopic vision. In 27 endovesical lymphographies the following lymph nodes could be demonstrated: the anterior, lateral and posterior vesical, the obturator, the external and internal iliac and the common iliac nodes."} {"id": "PMID:1278043", "title": "[Diabetes mellitus in idiopathic haemochromatosis (author's transl)].", "content": "In 28 out of 40 patients with idiopathic haemochromatosis manifest diabetes mellitus could be demonstrated 19 patients required insulin. Treatment of diabetes with or without insulin was problem-free. In only two patients there was an insulin resistance which required high doses of insulin some of the time. There was a family history of diabetes in eleven patients. Minimal diabetic retinopathy in two patients was the only typical complication specific to diabetes. Severe forms of microangiopathy are seldom seen in haemochromatosis diabetes. This form of diabetes is probably mainly of genetic origin. Liver cirrhosis and fibrosis and possibly pancreatic siderosis are additional factors to be considered. A sufficiently long and intensive venesection treatment leads to clinical improvement in the diabetes in only a small fraction of the haemochromatosis patients.", "contents": "[Diabetes mellitus in idiopathic haemochromatosis (author's transl)]. In 28 out of 40 patients with idiopathic haemochromatosis manifest diabetes mellitus could be demonstrated 19 patients required insulin. Treatment of diabetes with or without insulin was problem-free. In only two patients there was an insulin resistance which required high doses of insulin some of the time. There was a family history of diabetes in eleven patients. Minimal diabetic retinopathy in two patients was the only typical complication specific to diabetes. Severe forms of microangiopathy are seldom seen in haemochromatosis diabetes. This form of diabetes is probably mainly of genetic origin. Liver cirrhosis and fibrosis and possibly pancreatic siderosis are additional factors to be considered. A sufficiently long and intensive venesection treatment leads to clinical improvement in the diabetes in only a small fraction of the haemochromatosis patients."} {"id": "PMID:1278044", "title": "[On amnesic episodes (author's transl)].", "content": "Amnesic episodes occur suddenly out of full health and pass off spontaneously after about three to six hours. Consciousness and customary speech and action are maintained during these periods, but powers of acute observation and memory for preceding weeks are lost. But amnesia persists only for the events during the amnesic episode. Temporary and circumscribed ischaemia in the limbic system is thought to be the case. Three case reports are presented to illustrate precipitating circumstances.", "contents": "[On amnesic episodes (author's transl)]. Amnesic episodes occur suddenly out of full health and pass off spontaneously after about three to six hours. Consciousness and customary speech and action are maintained during these periods, but powers of acute observation and memory for preceding weeks are lost. But amnesia persists only for the events during the amnesic episode. Temporary and circumscribed ischaemia in the limbic system is thought to be the case. Three case reports are presented to illustrate precipitating circumstances."} {"id": "PMID:1278049", "title": "[Liver damage in chronic alcoholics with and without delirium tremens (author's transl)].", "content": "371 males admitted to a special hospital for withdrawal treatment of alcoholics were investigated on admission and repeatedly controlled during a follow-up of 3-6 months. In only 15% of all patients without delirium tremens there were no signs of liver disease on admission. 62% showed evidence of moderate or severe liver disease. 2-6 months after admission the percentage with moderate or severe liver disease had decreased (26%) while normal findings were obtained in 49%. On admission no correlation between frequency or degree of liver damage and the duration of alcohol abuse or daily intake of alcohol was demonstrated. Following abstinence of 2 months or more incidence of severe liver changes was nearly unchanged (16%) in patients drinking for more than 20 years, while it dropped distinctly in the groups with shorter duration of abuse (abuse less than 10 years: 5%). Histological alterations were distinctly more frequent in patients with abuse of more than 15 years (pronounced fibrosis 26%, cirrhosis 20%), as compared to alcoholics who drank less than 15 years (5 and 9%, respectively). In the patients with delirium tremens signs of severe liver disease were more frequent than in those without delirium. The trend towards normalisation of liver function tests was less in the former than in the latter (marked pathological findings following 2 months of alcohol abstinence in alcoholics with delirium tremens: duration of alcoholism less than 10 years: 16%; 11-20 years: 33%).", "contents": "[Liver damage in chronic alcoholics with and without delirium tremens (author's transl)]. 371 males admitted to a special hospital for withdrawal treatment of alcoholics were investigated on admission and repeatedly controlled during a follow-up of 3-6 months. In only 15% of all patients without delirium tremens there were no signs of liver disease on admission. 62% showed evidence of moderate or severe liver disease. 2-6 months after admission the percentage with moderate or severe liver disease had decreased (26%) while normal findings were obtained in 49%. On admission no correlation between frequency or degree of liver damage and the duration of alcohol abuse or daily intake of alcohol was demonstrated. Following abstinence of 2 months or more incidence of severe liver changes was nearly unchanged (16%) in patients drinking for more than 20 years, while it dropped distinctly in the groups with shorter duration of abuse (abuse less than 10 years: 5%). Histological alterations were distinctly more frequent in patients with abuse of more than 15 years (pronounced fibrosis 26%, cirrhosis 20%), as compared to alcoholics who drank less than 15 years (5 and 9%, respectively). In the patients with delirium tremens signs of severe liver disease were more frequent than in those without delirium. The trend towards normalisation of liver function tests was less in the former than in the latter (marked pathological findings following 2 months of alcohol abstinence in alcoholics with delirium tremens: duration of alcoholism less than 10 years: 16%; 11-20 years: 33%)."} {"id": "PMID:1278050", "title": "[Results of 201thallium myocardial scanning in coronary heart disease (author's transl)].", "content": "Quantifiable 201Tl scanning of the myocardium was performed in 23 patients with coronary heart disease and 10 without heart disease. Taking into consideration normal relative minimal storage of 201Tl in different regions of the myocardium (five projections), decreased 201Tl uptake in underperfused myocardium (acute myocardial infarction, coronary artery stenoses with hypo-, dys-, and akinesia) was recognizable according to extent and localisation (iso-impulse rate scan). The lowest relative 201Tl storage was found in dyskinesia or akinesia (37.6-54.1%) in the region of the anterior wall, as well as in acute myocardial infarction (50%). In the period after myocardial infarction persistence and normalisation of underperfusion could both be demonstrated. 201Tl scan as a non-invasive test is an appropriate means for demonstrating relative regional perfusion in the myocardium, with myocardial capacity for active uptake of potassium-like thallium being determined at the same time.", "contents": "[Results of 201thallium myocardial scanning in coronary heart disease (author's transl)]. Quantifiable 201Tl scanning of the myocardium was performed in 23 patients with coronary heart disease and 10 without heart disease. Taking into consideration normal relative minimal storage of 201Tl in different regions of the myocardium (five projections), decreased 201Tl uptake in underperfused myocardium (acute myocardial infarction, coronary artery stenoses with hypo-, dys-, and akinesia) was recognizable according to extent and localisation (iso-impulse rate scan). The lowest relative 201Tl storage was found in dyskinesia or akinesia (37.6-54.1%) in the region of the anterior wall, as well as in acute myocardial infarction (50%). In the period after myocardial infarction persistence and normalisation of underperfusion could both be demonstrated. 201Tl scan as a non-invasive test is an appropriate means for demonstrating relative regional perfusion in the myocardium, with myocardial capacity for active uptake of potassium-like thallium being determined at the same time."} {"id": "PMID:1278051", "title": "[Human coronary arterial patterns (author's transl)].", "content": "Limits of the supply area of the three large coronary arteries (right, left descending and left circumscribed branches) were determined by post-mortem angiography of 400 human hearts. The largest variation was demonstrated in the region of the posterior ventricular wall and the apex. Most frequently the border of the supply region between right and left circumflex branches extended across the middle of the left posterior wall. Hearts in which the left ventricular posterior wall was supplied from both right and left circumflex branches (normal type) constituted 82% of all cases. In the right-coronary dominant type (10%) the left ventricular posterior wall, at least at the base, was supplied by the right coronary artery, while in the left-dominant type (8%) the right coronary artery did not supply any part of the left posterior wall. At the apex the left descending branch rose dorsally by about 0.2-5.0 cm in 70% of cases, while the posterior interventricular branch only rarely supplied the apex (1.1%). The left coronary artery showed most variations in the anterior wall. It divided into two in 41%, into three with an additional diagonal branch in 53% and into four in 6%.", "contents": "[Human coronary arterial patterns (author's transl)]. Limits of the supply area of the three large coronary arteries (right, left descending and left circumscribed branches) were determined by post-mortem angiography of 400 human hearts. The largest variation was demonstrated in the region of the posterior ventricular wall and the apex. Most frequently the border of the supply region between right and left circumflex branches extended across the middle of the left posterior wall. Hearts in which the left ventricular posterior wall was supplied from both right and left circumflex branches (normal type) constituted 82% of all cases. In the right-coronary dominant type (10%) the left ventricular posterior wall, at least at the base, was supplied by the right coronary artery, while in the left-dominant type (8%) the right coronary artery did not supply any part of the left posterior wall. At the apex the left descending branch rose dorsally by about 0.2-5.0 cm in 70% of cases, while the posterior interventricular branch only rarely supplied the apex (1.1%). The left coronary artery showed most variations in the anterior wall. It divided into two in 41%, into three with an additional diagonal branch in 53% and into four in 6%."} {"id": "PMID:1278055", "title": "[Acute febrile neutrophilic dermatosis Sweet's syndrome].", "content": "Acute febrile neutrophilic dermatosis was diagnosed in three middle-aged women. It started characteristically one to three weeks after infection of the upper respiratory tract with sudden fever and painful, inflammatory, multiform skin lesions. There was marked leucocytosis and neutrophilia. The disease is characterized by dense, perivascular, neutrophil-granulocytic infiltrates associated with lymphocytic-histocytic reactions at the margins. Site and dynamics of the histological changes suggest an immune-complex disease. However, direct immunofluorescence has not given any characteristic findings. In general the prognosis is good, the disease rapidly responding to systemic glucocorticoids. But there are also spontaneous remissions, as in two of the described cases.", "contents": "[Acute febrile neutrophilic dermatosis Sweet's syndrome]. Acute febrile neutrophilic dermatosis was diagnosed in three middle-aged women. It started characteristically one to three weeks after infection of the upper respiratory tract with sudden fever and painful, inflammatory, multiform skin lesions. There was marked leucocytosis and neutrophilia. The disease is characterized by dense, perivascular, neutrophil-granulocytic infiltrates associated with lymphocytic-histocytic reactions at the margins. Site and dynamics of the histological changes suggest an immune-complex disease. However, direct immunofluorescence has not given any characteristic findings. In general the prognosis is good, the disease rapidly responding to systemic glucocorticoids. But there are also spontaneous remissions, as in two of the described cases."} {"id": "PMID:1278056", "title": "[Plasma aldosterone during haemodialysis in patients with terminal renal failure].", "content": "In 14 patients with terminal renal failure who underwent dialysis with a solution containing potassium in a concentration of 2 mmol/l, the aldosterone concentration in plasma decreased significantly during haemodialysis. On the other hand a clear increase of plasma aldosterone was observed during haemodialysis in two patients who were dialysed with a solution containing potassium in a concentration of 4 mmol/l. This observation demonstrates the importance of plasma potassium for the regulation of plasma aldosterone concentration during haemodialysis. It suggests that the renin-angiotensin system has no major role in the regulation of aldosterone despite sodium and fluid losses.", "contents": "[Plasma aldosterone during haemodialysis in patients with terminal renal failure]. In 14 patients with terminal renal failure who underwent dialysis with a solution containing potassium in a concentration of 2 mmol/l, the aldosterone concentration in plasma decreased significantly during haemodialysis. On the other hand a clear increase of plasma aldosterone was observed during haemodialysis in two patients who were dialysed with a solution containing potassium in a concentration of 4 mmol/l. This observation demonstrates the importance of plasma potassium for the regulation of plasma aldosterone concentration during haemodialysis. It suggests that the renin-angiotensin system has no major role in the regulation of aldosterone despite sodium and fluid losses."} {"id": "PMID:1278057", "title": "[Allergic agranulocytosis due to promethazine].", "content": "An allergic agranulocytosis developed after promethazine administration to a 34-year-old man with a compulsion neurosis. Promethazine-specific leucocyte antibodies were demonstrated in the antiglobulin consumption test. Four similar cases, reported in the literature, are discussed in relation to this personal case. The findings are contrasted to the majority of cases of toxic \"phenothiazine agranulocytosis\".", "contents": "[Allergic agranulocytosis due to promethazine]. An allergic agranulocytosis developed after promethazine administration to a 34-year-old man with a compulsion neurosis. Promethazine-specific leucocyte antibodies were demonstrated in the antiglobulin consumption test. Four similar cases, reported in the literature, are discussed in relation to this personal case. The findings are contrasted to the majority of cases of toxic \"phenothiazine agranulocytosis\"."} {"id": "PMID:1278060", "title": "The prevalence of hypertension in the United States today.", "content": "The simplest response to the question, what is the prevalence of hypertension in the United States today?, is given by a currently popular slogan: 23,000,000 Americans have hypertension. It is clear that the problem is large in scale, but this figure alone is an insufficient guide to many practical issues. The prevalence ratio underlying this estimate is about 15% for adults 18 to 79 years of age. Actual prevalence ratios may vary widely in specific sub-groups of the population and in accordance with differing methods and criteria of ascertainment. For example, the actual numbers of hypertensives in the general population of the US, detectable by two-stage screening, may be closer to 8 or 9 million. On the other hand, the current failure generally of detection of hypertension would suggest that the entire adult population must be screened periodically - and this number is greater than 126 million. The implications of these considerations for undertaking screening and management programmes are discussed briefly.", "contents": "The prevalence of hypertension in the United States today. The simplest response to the question, what is the prevalence of hypertension in the United States today?, is given by a currently popular slogan: 23,000,000 Americans have hypertension. It is clear that the problem is large in scale, but this figure alone is an insufficient guide to many practical issues. The prevalence ratio underlying this estimate is about 15% for adults 18 to 79 years of age. Actual prevalence ratios may vary widely in specific sub-groups of the population and in accordance with differing methods and criteria of ascertainment. For example, the actual numbers of hypertensives in the general population of the US, detectable by two-stage screening, may be closer to 8 or 9 million. On the other hand, the current failure generally of detection of hypertension would suggest that the entire adult population must be screened periodically - and this number is greater than 126 million. The implications of these considerations for undertaking screening and management programmes are discussed briefly."} {"id": "PMID:1278059", "title": "Clinical use of immunosuppressive drugs: part II.", "content": "In haematological diseases, insufficient data has been accumulated to evaluate the efficacy of immunosuppressive drug treatment in patients with erythroid aplasia or sideroblastic anaemia. Cyclophosphamide may be efficacious in inhibiting circulating anticoagulants in patients who need continued replacement of clotting factors. Azathioprine, 6-mercaptopurine, cyclophosphamide and vincristine have been used successfully in treating patients with idiopathic thrombocytopenic purpura, and some patients with auto-immune haemolytic anaemia may benefit from the addition of purine analogues. However, the use of immunosuppressive therapy seems to accelerate the presence of haematological malignancies in patients with macroglobulinaemia. In gastro-intestinal diseases, uncontrolled studies have shown nitrogen mustard, 6-mercaptopurine and azathioprine to be of modest benefit to patients with ulcerative colitis and Crohn's disease. In a controlled trial azathioprine plus prednisone proved more effective than prednisone alone in sustaining remission in patients with Crohn's disease. In patients with either chronic active hepatitis or primary biliary cirrhosis, however, there seems to be no benefit from immunosuppressive therapy for primary treatment of these diseases. Cyclophosphamide, azathioprine and methotrexate have all been used with some success in treating patient with uveitis, and in a controlled trial cytarabine has been shown to be beneficial to patients with herpes ophthalmicus. However, no benefit has been shown to patients with the eye changes of Graves' disease with either azathioprine or methotrexate. Patients with Paget's disease appear to be helped by mithramycin. Cyclophosphamide, chlorambucil and azathioprine are ineffective in treating patients with multiple sclerosis. 6-Mercaptopurine, azathioprine, methotrexate and cyclophosphamide have all produced some benefit in patients with myasthenia gravis, and some patients with idiopathic pulmonary haemosiderosis have responded to azathioprine, 6-mercaptopurine and cyclophosphamide. Alkylating agents have proved useful in treating some patients with asthma and in treating frequent relapsers among children with the nephrotic syndrome. In adults with membrano-proliferative glomerulonephritis some patients have responded to combination therapy with cyclophosphamide, azathioprine and corticosteroids. Immunosuppressive therapy is also indicated in prolonging graft survivals in patients receiving organ transplants. Drug toxicities of immunosuppressive agents are discussed. Their long-term effects, including mutagenic potential, have as yet not been fully elucidated.", "contents": "Clinical use of immunosuppressive drugs: part II. In haematological diseases, insufficient data has been accumulated to evaluate the efficacy of immunosuppressive drug treatment in patients with erythroid aplasia or sideroblastic anaemia. Cyclophosphamide may be efficacious in inhibiting circulating anticoagulants in patients who need continued replacement of clotting factors. Azathioprine, 6-mercaptopurine, cyclophosphamide and vincristine have been used successfully in treating patients with idiopathic thrombocytopenic purpura, and some patients with auto-immune haemolytic anaemia may benefit from the addition of purine analogues. However, the use of immunosuppressive therapy seems to accelerate the presence of haematological malignancies in patients with macroglobulinaemia. In gastro-intestinal diseases, uncontrolled studies have shown nitrogen mustard, 6-mercaptopurine and azathioprine to be of modest benefit to patients with ulcerative colitis and Crohn's disease. In a controlled trial azathioprine plus prednisone proved more effective than prednisone alone in sustaining remission in patients with Crohn's disease. In patients with either chronic active hepatitis or primary biliary cirrhosis, however, there seems to be no benefit from immunosuppressive therapy for primary treatment of these diseases. Cyclophosphamide, azathioprine and methotrexate have all been used with some success in treating patient with uveitis, and in a controlled trial cytarabine has been shown to be beneficial to patients with herpes ophthalmicus. However, no benefit has been shown to patients with the eye changes of Graves' disease with either azathioprine or methotrexate. Patients with Paget's disease appear to be helped by mithramycin. Cyclophosphamide, chlorambucil and azathioprine are ineffective in treating patients with multiple sclerosis. 6-Mercaptopurine, azathioprine, methotrexate and cyclophosphamide have all produced some benefit in patients with myasthenia gravis, and some patients with idiopathic pulmonary haemosiderosis have responded to azathioprine, 6-mercaptopurine and cyclophosphamide. Alkylating agents have proved useful in treating some patients with asthma and in treating frequent relapsers among children with the nephrotic syndrome. In adults with membrano-proliferative glomerulonephritis some patients have responded to combination therapy with cyclophosphamide, azathioprine and corticosteroids. Immunosuppressive therapy is also indicated in prolonging graft survivals in patients receiving organ transplants. Drug toxicities of immunosuppressive agents are discussed. Their long-term effects, including mutagenic potential, have as yet not been fully elucidated."} {"id": "PMID:1278061", "title": "Action of propranolol on arterial pressure and on cardiovascular reflexes.", "content": "In the rabbit, administration of 500 mug (+/-) propranolol into the lateral cerebral ventricle resulted in rapid leakage of drug into the blood. The drug produced a small reduction in blood pressure at 2 and 4 hours after injection but because of the rapid leakage, this could have been due to its peripheral actions. To investigate possible central mechanisms of action which were independent of peripheral effects, we tested the action of intravenously administered propranolol on the reflex rise in TPR evoked in rabbits by graded Valsalva-like manoeuvres. This was performed in unanaesthetised rabbits with Doppler flowmeters for measuring cardiac output. Graded expiratory pressures (EP) were applied to the inlet and outlet tubes of the tracheotomised animal's respiratory valve and to the cuff around their thorax and abdomen. Administration of propranolol at two levels (168 +/- 35 ng/ml, and 240 +/- 33 ng/ml) for 1 hour had no effect on slope and threshold of the EP-TPR relationship. By contrast to the minimal effects on the reflex with propranolol, the EP-related rise in TPR was attenuated by clonidine. We conclude that propranolol does not lower blood pressure in the rabbit by attenuating sympathetic constrictor activity.", "contents": "Action of propranolol on arterial pressure and on cardiovascular reflexes. In the rabbit, administration of 500 mug (+/-) propranolol into the lateral cerebral ventricle resulted in rapid leakage of drug into the blood. The drug produced a small reduction in blood pressure at 2 and 4 hours after injection but because of the rapid leakage, this could have been due to its peripheral actions. To investigate possible central mechanisms of action which were independent of peripheral effects, we tested the action of intravenously administered propranolol on the reflex rise in TPR evoked in rabbits by graded Valsalva-like manoeuvres. This was performed in unanaesthetised rabbits with Doppler flowmeters for measuring cardiac output. Graded expiratory pressures (EP) were applied to the inlet and outlet tubes of the tracheotomised animal's respiratory valve and to the cuff around their thorax and abdomen. Administration of propranolol at two levels (168 +/- 35 ng/ml, and 240 +/- 33 ng/ml) for 1 hour had no effect on slope and threshold of the EP-TPR relationship. By contrast to the minimal effects on the reflex with propranolol, the EP-related rise in TPR was attenuated by clonidine. We conclude that propranolol does not lower blood pressure in the rabbit by attenuating sympathetic constrictor activity."} {"id": "PMID:1278062", "title": "Blood pressure in middle-aged people in Albury and Melbourne - implications for screening.", "content": "Prevalence rates of hypertension and its treatment in two population samples of middle-aged people, one in Albury and one in Melbourne, are described. On average, Italian-born subjects had lower pressures than their Australian-born neighbours. The proportions of Australian-born people in the two centres who had been previously diagnosed were respectively 22% and 32% and the proportions with diastolic blood pressure greater than or equal to 110 mm Hg were 13% and 9%. About one half of the latter had never been told they had high blood pressure. Postal follow-up in the second post-survey year indicated that treatment rates had nearly doubled, many people with relatively low survey pressures stating they were now on therapy. Screening may precipitate over-use of antihypertensive drugs. The recent finding that 80% of middle-aged people in Albury had been to a doctor in the previous 12 months and that in a high proportion the blood pressure had been measured suggests that control of hypertension in Australia may be best achieved by developing surveillance in the context of ordinary medical practice.", "contents": "Blood pressure in middle-aged people in Albury and Melbourne - implications for screening. Prevalence rates of hypertension and its treatment in two population samples of middle-aged people, one in Albury and one in Melbourne, are described. On average, Italian-born subjects had lower pressures than their Australian-born neighbours. The proportions of Australian-born people in the two centres who had been previously diagnosed were respectively 22% and 32% and the proportions with diastolic blood pressure greater than or equal to 110 mm Hg were 13% and 9%. About one half of the latter had never been told they had high blood pressure. Postal follow-up in the second post-survey year indicated that treatment rates had nearly doubled, many people with relatively low survey pressures stating they were now on therapy. Screening may precipitate over-use of antihypertensive drugs. The recent finding that 80% of middle-aged people in Albury had been to a doctor in the previous 12 months and that in a high proportion the blood pressure had been measured suggests that control of hypertension in Australia may be best achieved by developing surveillance in the context of ordinary medical practice."} {"id": "PMID:1278063", "title": "Morbidity and mortality in hypertension.", "content": "There is substantial evidence of increased mortality and morbidity in hypertension. There is also clear evidence that antihypertensive treatment reduces the incidence of stroke and reduces the incidence of heart failure, but leaves myocardial infarction as a major cause of death and disability.", "contents": "Morbidity and mortality in hypertension. There is substantial evidence of increased mortality and morbidity in hypertension. There is also clear evidence that antihypertensive treatment reduces the incidence of stroke and reduces the incidence of heart failure, but leaves myocardial infarction as a major cause of death and disability."} {"id": "PMID:1278064", "title": "Hypertension and strokes.", "content": "Strokes are the third major cause of death in developed countries and are probably the major cause of severe chronic disability. Hypertension is the most important condition predisposing to strokes, and treatment of hypertension is of great importance in stroke prevention. The relationship of strokes to the degree of hypertension, and to age, sex, race and drug treatment is discussed.", "contents": "Hypertension and strokes. Strokes are the third major cause of death in developed countries and are probably the major cause of severe chronic disability. Hypertension is the most important condition predisposing to strokes, and treatment of hypertension is of great importance in stroke prevention. The relationship of strokes to the degree of hypertension, and to age, sex, race and drug treatment is discussed."} {"id": "PMID:1278065", "title": "Morbidity and mortality in untreated and treated hypertension: results from the G\u00f6teborg 50-year-old men study.", "content": "Total mortality, and mortality and morbidity from myocardial infarction, have been followed in one-thrid (n = 855) of a totoal male population from the age of 50 to the age of 60. An initial screening examination was performed in 1963 when the participants were 50 years old. Mortality data were gathered from death certificates and autopsies. Fatal and non-fatal myocardial infarction was followed by means of an infarction register. The participants were divided into four groups according to blood pressure in 1963 and the mortality and morbidity data in these 4 groups were compared with those who had been on antihypertensive treatment from 1963 to 1973.", "contents": "Morbidity and mortality in untreated and treated hypertension: results from the G\u00f6teborg 50-year-old men study. Total mortality, and mortality and morbidity from myocardial infarction, have been followed in one-thrid (n = 855) of a totoal male population from the age of 50 to the age of 60. An initial screening examination was performed in 1963 when the participants were 50 years old. Mortality data were gathered from death certificates and autopsies. Fatal and non-fatal myocardial infarction was followed by means of an infarction register. The participants were divided into four groups according to blood pressure in 1963 and the mortality and morbidity data in these 4 groups were compared with those who had been on antihypertensive treatment from 1963 to 1973."} {"id": "PMID:1278066", "title": "Mortality patterns in treated hypertension: results from Sydney Hospital.", "content": "A group of hypertensive patients, diastolic blood pressure 110 mm Hg or more and under the age of 60 years at the time of presentation, has been followed at the Cardiovascular Clinic, Sydney Hospital since 1955. Changes in the causes of death have been observed during the twenty-year period of observation. Patients with severe and treatment-resistant hypertension are likely to die of cerebro-vascular accidents, patients presenting with advanced retinopathy with papilloedema and established renal failure die predominantly of uraemia. The fate of patients with moderate degrees of blood pressure elevation, without papilloedema and with normal renal function, seems to be to succumb to the complications of ischaemic heart disease.", "contents": "Mortality patterns in treated hypertension: results from Sydney Hospital. A group of hypertensive patients, diastolic blood pressure 110 mm Hg or more and under the age of 60 years at the time of presentation, has been followed at the Cardiovascular Clinic, Sydney Hospital since 1955. Changes in the causes of death have been observed during the twenty-year period of observation. Patients with severe and treatment-resistant hypertension are likely to die of cerebro-vascular accidents, patients presenting with advanced retinopathy with papilloedema and established renal failure die predominantly of uraemia. The fate of patients with moderate degrees of blood pressure elevation, without papilloedema and with normal renal function, seems to be to succumb to the complications of ischaemic heart disease."} {"id": "PMID:1278067", "title": "New instruments for measuring blood pressure.", "content": "The development of the conventional indirect method of blood pressure measurement was essentially complete by 1905, 70 years ago. The method has certain shortcomings, but these can be offset to a large degree by control over conditions of measurement, provision of proper apparatus, and intensive training of observers. Still, there are potential advantages which might be met by an acceptable automated device. An experimental evaluation of five such devices led to rejection of each of them on grounds of inadequate measurement performance, mechanical failures, or both. Only the Random-Zero device (Hawksley) among the instruments tested, gave good performance in comparison with the conventional method and was free of serious mechanical disadvantages. Evaluation of new devices will continue to be of great importance, and proposed guidelines for such studies are reviewed.", "contents": "New instruments for measuring blood pressure. The development of the conventional indirect method of blood pressure measurement was essentially complete by 1905, 70 years ago. The method has certain shortcomings, but these can be offset to a large degree by control over conditions of measurement, provision of proper apparatus, and intensive training of observers. Still, there are potential advantages which might be met by an acceptable automated device. An experimental evaluation of five such devices led to rejection of each of them on grounds of inadequate measurement performance, mechanical failures, or both. Only the Random-Zero device (Hawksley) among the instruments tested, gave good performance in comparison with the conventional method and was free of serious mechanical disadvantages. Evaluation of new devices will continue to be of great importance, and proposed guidelines for such studies are reviewed."} {"id": "PMID:1278068", "title": "Pre-treatment workup for antihypertensive treatment.", "content": "The prevalence of primary and secondary hypertension and of heart and kidney involvement was thoroughly studied in 689 hypertensive subjects derived from a blood pressure screening examination of a total population sample of Swedish men (n = 7,452). The prevalence of secondary hypertension was found to be only 5%, the prevalence of surgically curable hypertension being even lower. Left ventricular hypertrophy and slight heart enlargement were each found in about one-third of the hypertensive patients, while severe heart enlargement, left ventricular hypertrophy on ECG, proteinuria, abnormal serum creatinine and urinary sediment were each found in about 5%. On the basis of these findings, a minimum pre-treatment workup in uncomplicated hypertension is proposed.", "contents": "Pre-treatment workup for antihypertensive treatment. The prevalence of primary and secondary hypertension and of heart and kidney involvement was thoroughly studied in 689 hypertensive subjects derived from a blood pressure screening examination of a total population sample of Swedish men (n = 7,452). The prevalence of secondary hypertension was found to be only 5%, the prevalence of surgically curable hypertension being even lower. Left ventricular hypertrophy and slight heart enlargement were each found in about one-third of the hypertensive patients, while severe heart enlargement, left ventricular hypertrophy on ECG, proteinuria, abnormal serum creatinine and urinary sediment were each found in about 5%. On the basis of these findings, a minimum pre-treatment workup in uncomplicated hypertension is proposed."} {"id": "PMID:1278069", "title": "The problem of non-compliance in long-term antihypertensive therapy.", "content": "Of 1,593 subjects admitted to the Australian National Blood Pressure Study 1 to 2 years ago, a substantial number (391 or 24.5%) ceased attending, in 85% of cases voluntarily. Withdrawal rates were very high in the first 4 months, settling to 5% per annum by the second year. Extrapolation to clinical practice is hazardous but contibutory factors elicited by questionnaire suggest certain management strategies: maximisation of efforts to enlist subject co-operation at the onset of treatment; management of treatment by family doctor or health centre with appointments flexible in time and infrequent in number; minimisation of doctors' ambivalence about treatment effectiveness and the withholding of information from the subject. It is inevitable that a proportion of subjects will reject long-term drug treatment. This adds further weight to the need for research on alternatives such as low salt diets.", "contents": "The problem of non-compliance in long-term antihypertensive therapy. Of 1,593 subjects admitted to the Australian National Blood Pressure Study 1 to 2 years ago, a substantial number (391 or 24.5%) ceased attending, in 85% of cases voluntarily. Withdrawal rates were very high in the first 4 months, settling to 5% per annum by the second year. Extrapolation to clinical practice is hazardous but contibutory factors elicited by questionnaire suggest certain management strategies: maximisation of efforts to enlist subject co-operation at the onset of treatment; management of treatment by family doctor or health centre with appointments flexible in time and infrequent in number; minimisation of doctors' ambivalence about treatment effectiveness and the withholding of information from the subject. It is inevitable that a proportion of subjects will reject long-term drug treatment. This adds further weight to the need for research on alternatives such as low salt diets."} {"id": "PMID:1278080", "title": "[Epithelial proliferations in organ cultures of mouse lung treated with urethane and 3,4-benzopyrene].", "content": "The authors carried out some series of experiments under the conditions of organ cultures of lungs of mice, treated with urethane and 3,4-benzpirene. They succeeded lung culturinf up to 14-th and 21-th day. Growths of bronchial and bronciolar epithelium manifested at various degree were obtained in the lung extracts from mice, treated with urethane and 3,4-benzpirene. The most manifested proliferation was observed in extracts, treated with urethane at a dose of 10 mg/ml and 3,4-benzpirene -- 64 gamma/ml.", "contents": "[Epithelial proliferations in organ cultures of mouse lung treated with urethane and 3,4-benzopyrene]. The authors carried out some series of experiments under the conditions of organ cultures of lungs of mice, treated with urethane and 3,4-benzpirene. They succeeded lung culturinf up to 14-th and 21-th day. Growths of bronchial and bronciolar epithelium manifested at various degree were obtained in the lung extracts from mice, treated with urethane and 3,4-benzpirene. The most manifested proliferation was observed in extracts, treated with urethane at a dose of 10 mg/ml and 3,4-benzpirene -- 64 gamma/ml."} {"id": "PMID:1278081", "title": "[Comparative studies of the vascularization of the posterior vena cava in some laboratory animals].", "content": "The author examined the posterior caval vena in four various areas in a rat, guinea pig, rabbit, cat and dog by applying Indian inkgelatine injection and subsequent preparation of histologic and total brighter preparations. The established differences in the vascularization were determined by the thickness of the true venous wall. The later increased with an increase of the body of the examined kind of animal on behalf of the adventitial longitudinal muscular layer at comparatively small differences in the thickness of the circular muscular layer in the media. There were no capilearies in the adventicial muscular layer of a rat and guinea pig. This layer was vascular, when the thickness of the true venous wall surpassed 70 microns. The most deeply penetrated capillaries were located almost equaly from the vascular lumen: 25 microns in the rabbit and 30 microns in the cat and dog.", "contents": "[Comparative studies of the vascularization of the posterior vena cava in some laboratory animals]. The author examined the posterior caval vena in four various areas in a rat, guinea pig, rabbit, cat and dog by applying Indian inkgelatine injection and subsequent preparation of histologic and total brighter preparations. The established differences in the vascularization were determined by the thickness of the true venous wall. The later increased with an increase of the body of the examined kind of animal on behalf of the adventitial longitudinal muscular layer at comparatively small differences in the thickness of the circular muscular layer in the media. There were no capilearies in the adventicial muscular layer of a rat and guinea pig. This layer was vascular, when the thickness of the true venous wall surpassed 70 microns. The most deeply penetrated capillaries were located almost equaly from the vascular lumen: 25 microns in the rabbit and 30 microns in the cat and dog."} {"id": "PMID:1278082", "title": "[Method for obtaining bile from rats in a chronic experiment].", "content": "The authors make a critical review of the methods, described in the literature for multiple samples of bile from rats under the conditions of a chronic experiment. They present their own method. The results from the follow-up of the dynamics in the bile cholinesterase activity in one of the rats canulated by this method are described.", "contents": "[Method for obtaining bile from rats in a chronic experiment]. The authors make a critical review of the methods, described in the literature for multiple samples of bile from rats under the conditions of a chronic experiment. They present their own method. The results from the follow-up of the dynamics in the bile cholinesterase activity in one of the rats canulated by this method are described."} {"id": "PMID:1278083", "title": "[Effect of cardiac glycosides on isoprenaline-induced heart changes].", "content": "The authors carried out studies on rats to examine the influence of preliminary treatment with strophanitine G on myocardial necrosis, induced by isoprenaline, evaluated by the changes in the number of leucocytes, erythrocyte sedimentation rate and the activity of SGPT in the peripheral blood, by the changes in the cardiac frequency and ECG as well as by the histologic and histochemical changes in the myocardium. It was established that strophanitine G potentiated the cardiotoxic action of isoprenaline, evaluated by hamatological, biochemical, electrocardiographic and histologic changes. The authors discuss the possible mechanisms of this interaction between digitalis glucoside and isoprenaline.", "contents": "[Effect of cardiac glycosides on isoprenaline-induced heart changes]. The authors carried out studies on rats to examine the influence of preliminary treatment with strophanitine G on myocardial necrosis, induced by isoprenaline, evaluated by the changes in the number of leucocytes, erythrocyte sedimentation rate and the activity of SGPT in the peripheral blood, by the changes in the cardiac frequency and ECG as well as by the histologic and histochemical changes in the myocardium. It was established that strophanitine G potentiated the cardiotoxic action of isoprenaline, evaluated by hamatological, biochemical, electrocardiographic and histologic changes. The authors discuss the possible mechanisms of this interaction between digitalis glucoside and isoprenaline."} {"id": "PMID:1278084", "title": "[Determination of the noradrenaline content and the noradrenaline metabolic rate in the brain of rats treated with lonetil].", "content": "Lonethyl1,2-methyl-3(para-etoxy-phanyl)-hynasolone-4, is an original Bulgarian preparation from the group of the tranquilizers. The authors examined its influence on the content of brain noradrenaline as well as on the velocity of noradrenaline exchange, which was the best index of sympathicus tonus. They used nonisotopic method of examining the velocity of noradrenaline exchange, which was based on measuring dimnution of the enodgenous mediator after blocking its biosynthesis. The studies were caried out on rats. The authors did not find changes both in the tissue concentration and in the velocity of noradrenaline exchange of animals, treated with lonethyl, which gave them foundation to include the preparation into the group of tranquilizers.", "contents": "[Determination of the noradrenaline content and the noradrenaline metabolic rate in the brain of rats treated with lonetil]. Lonethyl1,2-methyl-3(para-etoxy-phanyl)-hynasolone-4, is an original Bulgarian preparation from the group of the tranquilizers. The authors examined its influence on the content of brain noradrenaline as well as on the velocity of noradrenaline exchange, which was the best index of sympathicus tonus. They used nonisotopic method of examining the velocity of noradrenaline exchange, which was based on measuring dimnution of the enodgenous mediator after blocking its biosynthesis. The studies were caried out on rats. The authors did not find changes both in the tissue concentration and in the velocity of noradrenaline exchange of animals, treated with lonethyl, which gave them foundation to include the preparation into the group of tranquilizers."} {"id": "PMID:1278085", "title": "[Phagocytic function of the macrophages in leukemic animals].", "content": "The author carried out studies on 292 mice with transplantation leucosis. It was established that after alogenic transplantated leucosis the phagocytosis and digestion of the phaged objects by the peritoneal macrophages were enhanced. This effect lacked under syngenic conditions. The peritoneal cells of leucemic animals had higher phagocytosis of the purified peritoneal macrophages.", "contents": "[Phagocytic function of the macrophages in leukemic animals]. The author carried out studies on 292 mice with transplantation leucosis. It was established that after alogenic transplantated leucosis the phagocytosis and digestion of the phaged objects by the peritoneal macrophages were enhanced. This effect lacked under syngenic conditions. The peritoneal cells of leucemic animals had higher phagocytosis of the purified peritoneal macrophages."} {"id": "PMID:1278086", "title": "[Scanning electron microscopy of the lung in experimental collapse].", "content": "The author induced experimental lung collapse by means of ligating a bronch of a dog. The material was divided into six groups and was examined by a scanning electrone microscopy. Two phases in the development of the collapse were found. She indicated the advantages of the scanning electrone microscope in comparison with the light and the remaining electrone optical systems.", "contents": "[Scanning electron microscopy of the lung in experimental collapse]. The author induced experimental lung collapse by means of ligating a bronch of a dog. The material was divided into six groups and was examined by a scanning electrone microscopy. Two phases in the development of the collapse were found. She indicated the advantages of the scanning electrone microscope in comparison with the light and the remaining electrone optical systems."} {"id": "PMID:1278087", "title": "[Electron microscope studies of the kidney after its preservation at low temperatures].", "content": "Fragments the renal cortical part of white rats were frozened in two solutions: saline and 15% of glycerol. The preservation was made in liquid nitrogen (--196 degrees) for a period of 24 hours. The obtained results from the electrone microscopic examination showed that when freezing was performed without protective media, the intactness of the cells and their ultrastructural organization were destroyed. The nuclei preserved their intactness. When protective media (15% of glycerol) was used, then greater stability to low temperatures revealed the epitheleal cells, forming the glomerulus and intersticial tubules, but the most sensitive were the epithelial cells in the main part of the nephrone.", "contents": "[Electron microscope studies of the kidney after its preservation at low temperatures]. Fragments the renal cortical part of white rats were frozened in two solutions: saline and 15% of glycerol. The preservation was made in liquid nitrogen (--196 degrees) for a period of 24 hours. The obtained results from the electrone microscopic examination showed that when freezing was performed without protective media, the intactness of the cells and their ultrastructural organization were destroyed. The nuclei preserved their intactness. When protective media (15% of glycerol) was used, then greater stability to low temperatures revealed the epitheleal cells, forming the glomerulus and intersticial tubules, but the most sensitive were the epithelial cells in the main part of the nephrone."} {"id": "PMID:1278088", "title": "[Clinical and biochemical considerations on depressive states occuring during parkinsonian syndrome treated by L-Dopa].", "content": "From 17 observations of depressive illness occuring to parkinsonians treated with L. Dopa alone or associated with an inhibitor of peripheral decarboxylase, several types of depressive illness can be distinguished according to their date of appearance, their evolution with or without tricyclic anti-depressant drugs tertiary amine. According to the characteristics of these depressive illness, to the related locomotive state and to various monoamingeric hypothesises that are suggested both in the genesis of affective disorders and the mechanism of action of two biochemically related depressive aspects, a distinction already considered by other authors for endogeneous depressions.", "contents": "[Clinical and biochemical considerations on depressive states occuring during parkinsonian syndrome treated by L-Dopa]. From 17 observations of depressive illness occuring to parkinsonians treated with L. Dopa alone or associated with an inhibitor of peripheral decarboxylase, several types of depressive illness can be distinguished according to their date of appearance, their evolution with or without tricyclic anti-depressant drugs tertiary amine. According to the characteristics of these depressive illness, to the related locomotive state and to various monoamingeric hypothesises that are suggested both in the genesis of affective disorders and the mechanism of action of two biochemically related depressive aspects, a distinction already considered by other authors for endogeneous depressions."} {"id": "PMID:1278089", "title": "[Ectoparasites delusions in old age (Ekbom syndrome)].", "content": "The writers present the case of a patient diagnosed as suffering from a typical delusion of parasitosis which is also called \"Ekbom's Syndrom\". They remind the characteristics of an encapsulated delusional system. They try to show the particular role of semantic significations played by the words \"parasitis\" and \"skin\" as a defense against a death or inferiority anxiety in old patients.", "contents": "[Ectoparasites delusions in old age (Ekbom syndrome)]. The writers present the case of a patient diagnosed as suffering from a typical delusion of parasitosis which is also called \"Ekbom's Syndrom\". They remind the characteristics of an encapsulated delusional system. They try to show the particular role of semantic significations played by the words \"parasitis\" and \"skin\" as a defense against a death or inferiority anxiety in old patients."} {"id": "PMID:1278090", "title": "Effects of bone in vitro of bovine parathyroid hormone and synthetic fragments representing residues 1-34, 2-34 and 3-34.", "content": "The biological activities of bovine parathyroid hormone (BPTH) and fragments comprising portions of its amino-terminal sequence have been compared in three different assay systems using embryonic rat bone in vitro. Whereas the 3-34 fragment was without significant activity the 1-34 fragment caused all the actions characteristic of BPTH 1-84, extending to bone previous evidence that the amino-terminal residues are sufficient for expression of the biological effects of intact parathyroid hormone. However, the relative potencies of the fragment and the intact hormone were different in the various systems. BPTH 1-34 showed relatively low osteolytic activity and induced anabolic effects in both osteoblasts and cartilage cells of cultivated embryonic mouse radii which were not evoked by the intact hormone. Further work is required to determine the mechanisms responsible for these interesting alterations in relative potency of fragment and native hormone.", "contents": "Effects of bone in vitro of bovine parathyroid hormone and synthetic fragments representing residues 1-34, 2-34 and 3-34. The biological activities of bovine parathyroid hormone (BPTH) and fragments comprising portions of its amino-terminal sequence have been compared in three different assay systems using embryonic rat bone in vitro. Whereas the 3-34 fragment was without significant activity the 1-34 fragment caused all the actions characteristic of BPTH 1-84, extending to bone previous evidence that the amino-terminal residues are sufficient for expression of the biological effects of intact parathyroid hormone. However, the relative potencies of the fragment and the intact hormone were different in the various systems. BPTH 1-34 showed relatively low osteolytic activity and induced anabolic effects in both osteoblasts and cartilage cells of cultivated embryonic mouse radii which were not evoked by the intact hormone. Further work is required to determine the mechanisms responsible for these interesting alterations in relative potency of fragment and native hormone."} {"id": "PMID:1278091", "title": "The differential response of prostatic nucleolar and extra-nucleolar protein phosphokinase activities following androgen deprivation.", "content": "Protein phosphokinase activities of nucleolar and extra-nucleolar compartments of rat ventral prostate nuclei were measured using the model acidic phosphoprotein, dephosphophosvitin, as substrate. Following orchiectomy, the activity in both of these fractions declined; however, the kinase activity of the nucleolus decreased at a much greater rate than that in the extra-nucleolar portion of the nucleus. Testosterone maintenance of castrated animals prevented this decline in activity. The regulation of protein phosphokinases which phosphorylate prostatic nucleolar acidic proteins may be an important mechanism in the androgen mediated activation of the nucleolus in this target tissue.", "contents": "The differential response of prostatic nucleolar and extra-nucleolar protein phosphokinase activities following androgen deprivation. Protein phosphokinase activities of nucleolar and extra-nucleolar compartments of rat ventral prostate nuclei were measured using the model acidic phosphoprotein, dephosphophosvitin, as substrate. Following orchiectomy, the activity in both of these fractions declined; however, the kinase activity of the nucleolus decreased at a much greater rate than that in the extra-nucleolar portion of the nucleus. Testosterone maintenance of castrated animals prevented this decline in activity. The regulation of protein phosphokinases which phosphorylate prostatic nucleolar acidic proteins may be an important mechanism in the androgen mediated activation of the nucleolus in this target tissue."} {"id": "PMID:1278092", "title": "Rapid chromatography for quantitation of radioimmunoassayable 5alpha-androstane-17beta-ol-3-one and testesterone in ram, bull and boar serum.", "content": "A rapid technique for the simultaneous determination of serum 5alpha-androstane-17beta-0l-3-one (DHT) and testosterone (T) was developed and validated. The procedure incorporates a chromatographic step prior to binding with a T-3BSA antiserum. Anakrom columns used to separate DHT from T also isolate other steroids quickly and efficiently. Utilizing this procedure, levels of both androgens have been measured in the intact ram, bull and boar. Concentrations of DHT and T expressed as mean +/- SE in ng/ml were respectively: ram, 0.14 +/- 0.03 and 4.96 +/- 0.80; bull, 0.10 +/- 0.01 and 3.92 +/- 0.80; boar, 0.71 +/- 0.11 and 5.58 +/- 0.64. Whether these minute quantities of serum DHT play important physiological roles, particularly in the boar, is unresolved. Monitoring DHT under varying experimental or pathological conditions may allude to its importance in the domestic male.", "contents": "Rapid chromatography for quantitation of radioimmunoassayable 5alpha-androstane-17beta-ol-3-one and testesterone in ram, bull and boar serum. A rapid technique for the simultaneous determination of serum 5alpha-androstane-17beta-0l-3-one (DHT) and testosterone (T) was developed and validated. The procedure incorporates a chromatographic step prior to binding with a T-3BSA antiserum. Anakrom columns used to separate DHT from T also isolate other steroids quickly and efficiently. Utilizing this procedure, levels of both androgens have been measured in the intact ram, bull and boar. Concentrations of DHT and T expressed as mean +/- SE in ng/ml were respectively: ram, 0.14 +/- 0.03 and 4.96 +/- 0.80; bull, 0.10 +/- 0.01 and 3.92 +/- 0.80; boar, 0.71 +/- 0.11 and 5.58 +/- 0.64. Whether these minute quantities of serum DHT play important physiological roles, particularly in the boar, is unresolved. Monitoring DHT under varying experimental or pathological conditions may allude to its importance in the domestic male."} {"id": "PMID:1278093", "title": "The mechanism of action of the thioureylene antithyroid drugs.", "content": "A model incubation system containing purified thyroid peroxidase (TPO) was used to study the mechanism of action of the thioureylene anti-thyroid drugs--propylthiouracil (PTU), methylmercapto imidazole (MMI) and carbimazole. Two general types of experiments were performed: a) measurement of the inhibitory effects of the drugs on TPO-catalyzed iodination and on TPO-catalyzed oxidation of guaiacol, and b) studies of the metabolism of PTU and MMI by the TPO model system. The major observations can be summarized as follows: 1) The thioureylene drugs are potent inhibitors of TPO-catalyzed iodination of protein and tyrosine. Their potency increases greatly as the concentration of I- decreases. 2) The thioureylene drugs are also potent inhibitors of TPO-catalyzed oxidation of guaiacol, a reaction that does not involve iodide. 3) MMI and PTU are readily oxidized in the model incubation system when iodide is present but not in the absence of iodide. The rate of oxidation increased as the iodide concentration was increased from 10 to 100 muM. 4) Oxidation of PTU and MMI by the model incubation system is inhibited by relatively slight increases in the concentration of PTU and MMI. These drugs are capable of inhibiting their own and each other's metabolism. 5) Inhibition of iodination is competitively antagonized by iodide at low drug concentrations, but not at higher drug concentrations. 6) Inhibition of iodination by MMI and PTU may be either reversible (low ratio of drug to iodide), or irreversible (higher ratio of drug to iodide). In reversible inhibition the iodination is inhibited for a period which may be as brief as 2 min or as long as 20 min, but thereafter, iodination begins, and there is escape from inhibition. During the lag-period there is extensive metabolism of the drug. In the case of irreversible inhibition of iodination is inhibited completely or almost completely for 60 min, and drug oxidation during this period is relatively low. 7) Irreversible inhibition may be transformed into reversible inhibition by increasing the concentration of TPO or the concentration of iodide. However, increasing the concentration of H2O2 or of tyrosine does not overcome irreversible inhibition. On the basis of these findings and of current views concerning the mechanism of enzymatic iodination, a scheme is proposed for the mechanism of inhibition by thioureylene drugs of TPO-catalyzed iodination of protein and tyrosine.", "contents": "The mechanism of action of the thioureylene antithyroid drugs. A model incubation system containing purified thyroid peroxidase (TPO) was used to study the mechanism of action of the thioureylene anti-thyroid drugs--propylthiouracil (PTU), methylmercapto imidazole (MMI) and carbimazole. Two general types of experiments were performed: a) measurement of the inhibitory effects of the drugs on TPO-catalyzed iodination and on TPO-catalyzed oxidation of guaiacol, and b) studies of the metabolism of PTU and MMI by the TPO model system. The major observations can be summarized as follows: 1) The thioureylene drugs are potent inhibitors of TPO-catalyzed iodination of protein and tyrosine. Their potency increases greatly as the concentration of I- decreases. 2) The thioureylene drugs are also potent inhibitors of TPO-catalyzed oxidation of guaiacol, a reaction that does not involve iodide. 3) MMI and PTU are readily oxidized in the model incubation system when iodide is present but not in the absence of iodide. The rate of oxidation increased as the iodide concentration was increased from 10 to 100 muM. 4) Oxidation of PTU and MMI by the model incubation system is inhibited by relatively slight increases in the concentration of PTU and MMI. These drugs are capable of inhibiting their own and each other's metabolism. 5) Inhibition of iodination is competitively antagonized by iodide at low drug concentrations, but not at higher drug concentrations. 6) Inhibition of iodination by MMI and PTU may be either reversible (low ratio of drug to iodide), or irreversible (higher ratio of drug to iodide). In reversible inhibition the iodination is inhibited for a period which may be as brief as 2 min or as long as 20 min, but thereafter, iodination begins, and there is escape from inhibition. During the lag-period there is extensive metabolism of the drug. In the case of irreversible inhibition of iodination is inhibited completely or almost completely for 60 min, and drug oxidation during this period is relatively low. 7) Irreversible inhibition may be transformed into reversible inhibition by increasing the concentration of TPO or the concentration of iodide. However, increasing the concentration of H2O2 or of tyrosine does not overcome irreversible inhibition. On the basis of these findings and of current views concerning the mechanism of enzymatic iodination, a scheme is proposed for the mechanism of inhibition by thioureylene drugs of TPO-catalyzed iodination of protein and tyrosine."} {"id": "PMID:1278094", "title": "The influence of cholinergic, adrenergic, and serotonergic drugs on the afternoon surge of plasma prolactin in ovariectomized, estrogen-treated rats.", "content": "The effects of systemic administration of cholinergic, adrenergic, and serotonergic drugs on the afternoon surge of plasma prolactin was investigated using ovariectomized, polyestradiol phosphate (PEP)-injected rats bearing aortic catheters. Basal prolactin levels were elevated and similar after PEP administration for a period of 5 weeks, and an afternoon surge in plasma prolactin persisted for a period of 3 weeks before the magnitude of the surge diminished. The plasma estradiol levels were significantly higher for the 1100 and 1300 h samples than for the 1500 and 1700 h samples. Cornified vaginal epithelia were predominant in the vaginal smears of all animals throughout the 49-day experimental period. The cholinergic agonists arecoline, nicotine, and carbachol significantly inhibited the afternoon surge of prolactin. The muscarinic antagonist atropine resulted in a partial inhibition of the surge while the nicotinic antagonist mecamylamine did not have any inhibitory effect. The alpha-adrenergic blockers phenoxybenzamine and phentolamine and the beta-blocker propranolol inhibited the prolactin surge, with phenoxybenzamine being most effective. The administration of the serotonergic antagonist methysergide resulted in only a partial blockade of the afternoon prolactin surge. The data suggest that both the adrenergic and serotonergic systems may have a positive input in the afternoon surge of plasma prolactin. It appears that the cholinergic system does not play a significant role in the afternoon surge.", "contents": "The influence of cholinergic, adrenergic, and serotonergic drugs on the afternoon surge of plasma prolactin in ovariectomized, estrogen-treated rats. The effects of systemic administration of cholinergic, adrenergic, and serotonergic drugs on the afternoon surge of plasma prolactin was investigated using ovariectomized, polyestradiol phosphate (PEP)-injected rats bearing aortic catheters. Basal prolactin levels were elevated and similar after PEP administration for a period of 5 weeks, and an afternoon surge in plasma prolactin persisted for a period of 3 weeks before the magnitude of the surge diminished. The plasma estradiol levels were significantly higher for the 1100 and 1300 h samples than for the 1500 and 1700 h samples. Cornified vaginal epithelia were predominant in the vaginal smears of all animals throughout the 49-day experimental period. The cholinergic agonists arecoline, nicotine, and carbachol significantly inhibited the afternoon surge of prolactin. The muscarinic antagonist atropine resulted in a partial inhibition of the surge while the nicotinic antagonist mecamylamine did not have any inhibitory effect. The alpha-adrenergic blockers phenoxybenzamine and phentolamine and the beta-blocker propranolol inhibited the prolactin surge, with phenoxybenzamine being most effective. The administration of the serotonergic antagonist methysergide resulted in only a partial blockade of the afternoon prolactin surge. The data suggest that both the adrenergic and serotonergic systems may have a positive input in the afternoon surge of plasma prolactin. It appears that the cholinergic system does not play a significant role in the afternoon surge."} {"id": "PMID:1278095", "title": "Progesterone and estrogen control of uterine prostaglandin dehydrogenase activity during deciduomal growth.", "content": "Prostaglandin, dehydrogenase activity was determined in deciduomal and myometrial tissues during growth and regression of the deciduoma during pseudopregnancy. The hormonal control of prostaglandin dehydrogenase activity in these tissues was determined in experiments with ovariectomized pseudopregnant rats. Prostaglandin dehydrogenase activity for both prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in deciduomal and myometrial tissues increased during the growth of the deciduoma and decreased during the regression phase. No prostaglandin dehydrogenase activity was detected in non-decidualized pseudopregnant rat uteri. In ovarictomized pseudopregnant rats, progesterone and estrogen increased prostaglandin dehydrogenase activity for PGE1 in the deciduoma and myometrium; no synergistic action of the hormones was observed. Progesterone increased prostaglandin dehydrogenase activity for PGF2alpha in the deciduoma, but had no effect in the myometrium. The increases during decidualization in dehydrogenase activity for PGE1 and PGF2alpha, and the enhanced inactivation of these luteolytic substances would provide an explantation for the prolonged pseudopregnancy which results from decidualization of the uterus.", "contents": "Progesterone and estrogen control of uterine prostaglandin dehydrogenase activity during deciduomal growth. Prostaglandin, dehydrogenase activity was determined in deciduomal and myometrial tissues during growth and regression of the deciduoma during pseudopregnancy. The hormonal control of prostaglandin dehydrogenase activity in these tissues was determined in experiments with ovariectomized pseudopregnant rats. Prostaglandin dehydrogenase activity for both prostaglandin E1 (PGE1) and prostaglandin F2alpha (PGF2alpha) in deciduomal and myometrial tissues increased during the growth of the deciduoma and decreased during the regression phase. No prostaglandin dehydrogenase activity was detected in non-decidualized pseudopregnant rat uteri. In ovarictomized pseudopregnant rats, progesterone and estrogen increased prostaglandin dehydrogenase activity for PGE1 in the deciduoma and myometrium; no synergistic action of the hormones was observed. Progesterone increased prostaglandin dehydrogenase activity for PGF2alpha in the deciduoma, but had no effect in the myometrium. The increases during decidualization in dehydrogenase activity for PGE1 and PGF2alpha, and the enhanced inactivation of these luteolytic substances would provide an explantation for the prolonged pseudopregnancy which results from decidualization of the uterus."} {"id": "PMID:1278096", "title": "Relaxin concentrations in pig plasma following the administration of prostaglandin F2alpha during late pregnancy.", "content": "Concentrations of relaxin in peripheral plasma were measured following the injection of 10 mg of PGF2alpha to pregnant sows on day 112 of gestation. The mean concentrations of relaxin before injection of PGF2alpha were less than 13 ng/ml. Relaxin concentrations increased sharply to a mean of 104 ng/ml by 45 min following injection of PGF2alpha and then fell rapidly to a mean of 40 ng/ml 4 h later. Following this initial peak of relaxin, there was a gradual rise and fall of relaxin concentrations during the day preceding parturition. The levels of relaxin during this period were also influenced by PGF2alpha administration since the mean levels of relaxin were significantly lower from the 22nd through the 10th h before parturition in pigs given PGF2alpha, than in pigs given saline.", "contents": "Relaxin concentrations in pig plasma following the administration of prostaglandin F2alpha during late pregnancy. Concentrations of relaxin in peripheral plasma were measured following the injection of 10 mg of PGF2alpha to pregnant sows on day 112 of gestation. The mean concentrations of relaxin before injection of PGF2alpha were less than 13 ng/ml. Relaxin concentrations increased sharply to a mean of 104 ng/ml by 45 min following injection of PGF2alpha and then fell rapidly to a mean of 40 ng/ml 4 h later. Following this initial peak of relaxin, there was a gradual rise and fall of relaxin concentrations during the day preceding parturition. The levels of relaxin during this period were also influenced by PGF2alpha administration since the mean levels of relaxin were significantly lower from the 22nd through the 10th h before parturition in pigs given PGF2alpha, than in pigs given saline."} {"id": "PMID:1278097", "title": "Actions of angiotensin II antagonists upon aldosterone production by isolated adrenal glomerulosa cells.", "content": "The biological activities of angiotensin II antagonists upon basal and angiotensin II-stimulated aldosterone production were evaluated in an isolated canine glomerulosa cell preparation. The most potent competitive antagonist of angiotensin II-stimulated aldosterone production was the [Sar1, Ile8]derivative of angiotensin II. However, this peptide was also a partial agonist at concentrations required to inhibit the steroidogenic effect of angiotensin II on dog adrenal cells, and never reduced aldosterone production to basal levels. On a molar basis, the [Sar1, Ala8] and [Sar1, Gly8]derivatives of angiotensin II were relatively less potent as competitive inhibitors of angiotensin II-stimulated aldosterone production. However, the [Ala8] and [Gly8]-analogues did not exhibit significant agonist activity and were therefore more effective antagonists of angiontensin II-stimulated aldosterone production. These results suggest that increased length of the aliphatic side chain at the C-terminus of angiotensin II antagonists is accompanied by enhanced affinity for the receptor site, but also by increased agonist activity upon aldosterone synthesis. The actions of angiotensin II and [Des-Asp1]angiotensin II upon aldosterone production were inhibited identically and completely by [Sar1, Ala8]angiotensin II, and identically, though incompletely, by lower concentrations of [Sar1, Ile8]angiotensin II. The heptapeptide antagonist [Des-Asp1, Ile8]angiotensin II was much less potent than [Sar1, Ile8]angiotensin II as an inhibitor of the actions of both the heptapeptide and octapeptide agonists. The antagonist activity of six angiotensin II analogues at the adrenal level, determined by the concentration required for 50% inhibition of maximum aldosterone secretion, correlated well with their antagonist activity measured upon isolated smooth muscle. These observations demonstrate that the octapeptide antagonists are more effective than the heptapeptide antagonists upon angiotensin II-stimulated aldosterone production, and that angiotensin II receptors in smooth muscle and adrenal cortex exhibit generally similar responses to angiotensin II antagonists. Also, these results do not support the proposal that the [Des-Asp1]heptapeptide is an important intermediate in the action of angiotensin II upon adolesterone production in the adrenal glomerulosa cells. The production of aldosterone by dispersed zona glomerulosa cells in vitro provides a highly sensitive and biologically appropriate response for evaluation of the agonist and antagonist properties of angiotensin II analogues upon the adrenal gland.", "contents": "Actions of angiotensin II antagonists upon aldosterone production by isolated adrenal glomerulosa cells. The biological activities of angiotensin II antagonists upon basal and angiotensin II-stimulated aldosterone production were evaluated in an isolated canine glomerulosa cell preparation. The most potent competitive antagonist of angiotensin II-stimulated aldosterone production was the [Sar1, Ile8]derivative of angiotensin II. However, this peptide was also a partial agonist at concentrations required to inhibit the steroidogenic effect of angiotensin II on dog adrenal cells, and never reduced aldosterone production to basal levels. On a molar basis, the [Sar1, Ala8] and [Sar1, Gly8]derivatives of angiotensin II were relatively less potent as competitive inhibitors of angiotensin II-stimulated aldosterone production. However, the [Ala8] and [Gly8]-analogues did not exhibit significant agonist activity and were therefore more effective antagonists of angiontensin II-stimulated aldosterone production. These results suggest that increased length of the aliphatic side chain at the C-terminus of angiotensin II antagonists is accompanied by enhanced affinity for the receptor site, but also by increased agonist activity upon aldosterone synthesis. The actions of angiotensin II and [Des-Asp1]angiotensin II upon aldosterone production were inhibited identically and completely by [Sar1, Ala8]angiotensin II, and identically, though incompletely, by lower concentrations of [Sar1, Ile8]angiotensin II. The heptapeptide antagonist [Des-Asp1, Ile8]angiotensin II was much less potent than [Sar1, Ile8]angiotensin II as an inhibitor of the actions of both the heptapeptide and octapeptide agonists. The antagonist activity of six angiotensin II analogues at the adrenal level, determined by the concentration required for 50% inhibition of maximum aldosterone secretion, correlated well with their antagonist activity measured upon isolated smooth muscle. These observations demonstrate that the octapeptide antagonists are more effective than the heptapeptide antagonists upon angiotensin II-stimulated aldosterone production, and that angiotensin II receptors in smooth muscle and adrenal cortex exhibit generally similar responses to angiotensin II antagonists. Also, these results do not support the proposal that the [Des-Asp1]heptapeptide is an important intermediate in the action of angiotensin II upon adolesterone production in the adrenal glomerulosa cells. The production of aldosterone by dispersed zona glomerulosa cells in vitro provides a highly sensitive and biologically appropriate response for evaluation of the agonist and antagonist properties of angiotensin II analogues upon the adrenal gland."} {"id": "PMID:1278098", "title": "Lack of gonadotropic activity in the rabbit blastocyst prior to implantation.", "content": "Recent reports of an LH-like hormone in the rabbit preimplantation blastocyst and of elevated serum progesterone levels in the presence of unimplanted blastocysts prompted us to characterized further the biological activity of the presumed gonadotropin. Progesterone was measured by a highly specific radioimmunoassay in sera obtained from pregnant and pseudopregnant rabbits after mating (day 0) to fertile or vasectomized males. On days 3, 4, 5, and 6, which represent the preimplantation period, mean progesterone concentrations (ng/ml +/- SE) were 4.3 +/- 0.7, 5.1 +/- 0.5, 6.8 +/- 1.1, and 9.0 +/- 1.9 in 5 pseudopregnant rabbits and 4.1 +/- 0.4, 6.7 +/- 0.6, 5.9 +/- 0.9, and 7.0 +/- 0.8 in 7 pregnant rabbits. In a separate experiment, serum progesterone concentrations in 6 pseudopregnant and 8 pregnant rabbits were 10.1 +/- 0.7 ng/ml and 13.7 +/- 1.1 (P less than 0.02), respectively on days 11-12. Thus, serum progesterone concentrations were not different in pregnant and pseudopregnant rabbits before the time of implantation (day 7), but were higher in pregnant rabbits after implantation. Blastocysts obtained on day 6 and incubated with a cell suspension of immature rat ovaries failed to stimulate the accumulation of progesterone in medium, in contrast to hCG, which was active even in the presence of blastocysts. Day-6 blastocysts also failed to stimulate the accumulation of testosterone from decapsulated rat testes and of progesterone from rabbit ovarian tissues in vitro. A gonadotropic effect of the conceptus can be observed in the rabbit within 4 to 5 days after implantation. However, we find no evidence for the existence of an LH-like hormone in the preimplantation blastocyst which stimulates the rabbit ovary to secrete progesterone.", "contents": "Lack of gonadotropic activity in the rabbit blastocyst prior to implantation. Recent reports of an LH-like hormone in the rabbit preimplantation blastocyst and of elevated serum progesterone levels in the presence of unimplanted blastocysts prompted us to characterized further the biological activity of the presumed gonadotropin. Progesterone was measured by a highly specific radioimmunoassay in sera obtained from pregnant and pseudopregnant rabbits after mating (day 0) to fertile or vasectomized males. On days 3, 4, 5, and 6, which represent the preimplantation period, mean progesterone concentrations (ng/ml +/- SE) were 4.3 +/- 0.7, 5.1 +/- 0.5, 6.8 +/- 1.1, and 9.0 +/- 1.9 in 5 pseudopregnant rabbits and 4.1 +/- 0.4, 6.7 +/- 0.6, 5.9 +/- 0.9, and 7.0 +/- 0.8 in 7 pregnant rabbits. In a separate experiment, serum progesterone concentrations in 6 pseudopregnant and 8 pregnant rabbits were 10.1 +/- 0.7 ng/ml and 13.7 +/- 1.1 (P less than 0.02), respectively on days 11-12. Thus, serum progesterone concentrations were not different in pregnant and pseudopregnant rabbits before the time of implantation (day 7), but were higher in pregnant rabbits after implantation. Blastocysts obtained on day 6 and incubated with a cell suspension of immature rat ovaries failed to stimulate the accumulation of progesterone in medium, in contrast to hCG, which was active even in the presence of blastocysts. Day-6 blastocysts also failed to stimulate the accumulation of testosterone from decapsulated rat testes and of progesterone from rabbit ovarian tissues in vitro. A gonadotropic effect of the conceptus can be observed in the rabbit within 4 to 5 days after implantation. However, we find no evidence for the existence of an LH-like hormone in the preimplantation blastocyst which stimulates the rabbit ovary to secrete progesterone."} {"id": "PMID:1278099", "title": "Feminization of hepatic steroid metabolism in male rats following electrothermic lesion of the hypothalamus.", "content": "The metabolism of [4-14C]androst-4-ene-3,17-dione, [4-14C]5alpha-androstane-3alpha,17beta-diol and [1,2-3H]5alpha-androstane-3alpha,17beta-diol, 3,17-disulfate in the 105,000 X g supernatant and microsomal fractions of liver was studied in male and female rats after electrothermic lesion of the hypothalamus including the median eminence. Following electrothermic lesion, hepatic steroid metabolism in male rats was generally \"feminized\" (increased 5alpha-reduction and decreased 6beta- and 16alpha-hydroxylation of 4-androstene-3,17-dione, decreased 2alpha-, 2beta-, 18- and 7beta-hydroxylation of 5alpha-androstane-3alpha, 17beta-diol and induced 15beta-hydroxylation of 5alpha-androstane-3alpha,17beta-diol,3,17-disulfate), whereas hepatic metabolism in female rats remained essentially unchanged. Previous investigations have pointed to the occurrence of a sex-specific secretion of \"feminizing factor\" from the female pituitary that is responsible for the \"feminization\" of the basically \"masculine\" type of metabolism characterizing the rat liver. Taken together with these findings, the present results indicate that the release of the pituitary \"feminizing factor\" is controlled by means of a release-inhibiting factor from the hypothalamus. This factor is not secreted in female rats; it is suggested that its secretion in male rats is turned on as a result of neonatal imprinting by testicular androgens.", "contents": "Feminization of hepatic steroid metabolism in male rats following electrothermic lesion of the hypothalamus. The metabolism of [4-14C]androst-4-ene-3,17-dione, [4-14C]5alpha-androstane-3alpha,17beta-diol and [1,2-3H]5alpha-androstane-3alpha,17beta-diol, 3,17-disulfate in the 105,000 X g supernatant and microsomal fractions of liver was studied in male and female rats after electrothermic lesion of the hypothalamus including the median eminence. Following electrothermic lesion, hepatic steroid metabolism in male rats was generally \"feminized\" (increased 5alpha-reduction and decreased 6beta- and 16alpha-hydroxylation of 4-androstene-3,17-dione, decreased 2alpha-, 2beta-, 18- and 7beta-hydroxylation of 5alpha-androstane-3alpha, 17beta-diol and induced 15beta-hydroxylation of 5alpha-androstane-3alpha,17beta-diol,3,17-disulfate), whereas hepatic metabolism in female rats remained essentially unchanged. Previous investigations have pointed to the occurrence of a sex-specific secretion of \"feminizing factor\" from the female pituitary that is responsible for the \"feminization\" of the basically \"masculine\" type of metabolism characterizing the rat liver. Taken together with these findings, the present results indicate that the release of the pituitary \"feminizing factor\" is controlled by means of a release-inhibiting factor from the hypothalamus. This factor is not secreted in female rats; it is suggested that its secretion in male rats is turned on as a result of neonatal imprinting by testicular androgens."} {"id": "PMID:1278100", "title": "Effects of ovariectomy and season on plasma luteinizing hormone in mares.", "content": "Six pony mares were ovariectomized (OVX) on day 16 of diestrus during June and July, 1972, to study short term changes in plasma luteinizing hormone (LH) concentrations. Plasma LH was higher (P less than .05) 3 days after OVX (1.76 ng/ml) than the day after OVX (1.01 ng/ml), and a gradual increase occurred over the first 2 weeks. Elevated plasma LH concentrations similar to mid-estrus levels were present from the 2nd to 11th week post-OVX. In another experiment, the same 6 OVX mares were bled once a month from February, 1973, to January, 1974, to study long-term changes in plasma LH in relation to the anestrous (November-April) and breeding seasons (May-October). Mean monthly plasma LH concentrations in OVX mares during all months of the anestrous season were lower (P less than .05) than mean monthly plasma LH during the months of June-September of the breeding season. During the transition from anestrous to breeding seasons (April, May) and breeding to anestrous seasons October, November), mean plasma LH concentrations were not significantly different between April and May (1.39 vs 1.84 ng/ml) and between October and November (3.02 vs 2.56 ng/ml), but April and May levels were lower (P less than .05) than October and November levels. Mean monthly plasma LH levels in OVX mares during the anestrous season were similar to those in intact mares during the anestrous season and at mid-diestrus during the breeding season. Mean monthly plasma LH levels in OVX mares during the breeding season were similar to plasma LH levels at mild-estrus in intact mares. These data indicate the presence of inhibitory (most likely progesterone) and stimulatory (most likely estrogen) influences from the ovary which modulate the endogenous LH pattern in mares during the breeding season.", "contents": "Effects of ovariectomy and season on plasma luteinizing hormone in mares. Six pony mares were ovariectomized (OVX) on day 16 of diestrus during June and July, 1972, to study short term changes in plasma luteinizing hormone (LH) concentrations. Plasma LH was higher (P less than .05) 3 days after OVX (1.76 ng/ml) than the day after OVX (1.01 ng/ml), and a gradual increase occurred over the first 2 weeks. Elevated plasma LH concentrations similar to mid-estrus levels were present from the 2nd to 11th week post-OVX. In another experiment, the same 6 OVX mares were bled once a month from February, 1973, to January, 1974, to study long-term changes in plasma LH in relation to the anestrous (November-April) and breeding seasons (May-October). Mean monthly plasma LH concentrations in OVX mares during all months of the anestrous season were lower (P less than .05) than mean monthly plasma LH during the months of June-September of the breeding season. During the transition from anestrous to breeding seasons (April, May) and breeding to anestrous seasons October, November), mean plasma LH concentrations were not significantly different between April and May (1.39 vs 1.84 ng/ml) and between October and November (3.02 vs 2.56 ng/ml), but April and May levels were lower (P less than .05) than October and November levels. Mean monthly plasma LH levels in OVX mares during the anestrous season were similar to those in intact mares during the anestrous season and at mid-diestrus during the breeding season. Mean monthly plasma LH levels in OVX mares during the breeding season were similar to plasma LH levels at mild-estrus in intact mares. These data indicate the presence of inhibitory (most likely progesterone) and stimulatory (most likely estrogen) influences from the ovary which modulate the endogenous LH pattern in mares during the breeding season."} {"id": "PMID:1278101", "title": "Enzymatic sulfation of steroids: I. The enzymatic basis for the sex difference in cortisol sulfation by rat liver preparations.", "content": "Liver cytosols from female rats contained 6-8 times as much cortisol sulfotransferase activity as those from males. The reaction product, with both sexes, appeared to be cortisol-21 sulfate. Liver cytosols from male and female rats showed different substrate preferences when tested with cortisol, estradiol-17beta, testosterone, and dehydroepiandrosterone, suggesting that they contained different steroid sulfotransferases. Fractionation of cytosols from female rats on DEAE Sephadex A-50 columns resolved 3 steroid sulfotransferases, or families of steroid sulfotransferases (STI, STII, and STIII). These enzymes exhibited different substrate preferences. STI and STIII had the greatest preferences for cortisol, although none of the enzymes was restricted to the glucocorticoid. Fractionation of cytosols from males resolved 2 sulfotransferases which eluted at salt concentrations identical to STII and STIII from females. Study of the development of cortisol sulfotransferase activity with age showed little enzyme activity in rats of either sex at 2 days after birth. Enzyme activity developed in parallel in both sexes until 30 days after birth. Then the sulfotransferase activity began to rise in females and to drop in males. By day 50-55 both sexes attained adult enzyme levels. STII was the major enzyme in all immature animals. STIII was also present, but STI was absent. In male rats STIII activity began to rise by day 30. Soon after, STII activity began to drop. By day 55 adult male patterns developed. STI was the major enzyme in females by day 30. In ensuing days all 3 enzyme levels rose, until by day 50 adult enzyme patterns and levels were attained. The data suggest that the ovaries stimulated production of all 3 sulfotransferases and that the testes suppressed production of STII (and perhaps STI). Preliminary studies with gonadectomized rats supported the suppressive role of the testes, but suggested that the ovaries were not the only factor controlling sulfotransferase production in female rats.", "contents": "Enzymatic sulfation of steroids: I. The enzymatic basis for the sex difference in cortisol sulfation by rat liver preparations. Liver cytosols from female rats contained 6-8 times as much cortisol sulfotransferase activity as those from males. The reaction product, with both sexes, appeared to be cortisol-21 sulfate. Liver cytosols from male and female rats showed different substrate preferences when tested with cortisol, estradiol-17beta, testosterone, and dehydroepiandrosterone, suggesting that they contained different steroid sulfotransferases. Fractionation of cytosols from female rats on DEAE Sephadex A-50 columns resolved 3 steroid sulfotransferases, or families of steroid sulfotransferases (STI, STII, and STIII). These enzymes exhibited different substrate preferences. STI and STIII had the greatest preferences for cortisol, although none of the enzymes was restricted to the glucocorticoid. Fractionation of cytosols from males resolved 2 sulfotransferases which eluted at salt concentrations identical to STII and STIII from females. Study of the development of cortisol sulfotransferase activity with age showed little enzyme activity in rats of either sex at 2 days after birth. Enzyme activity developed in parallel in both sexes until 30 days after birth. Then the sulfotransferase activity began to rise in females and to drop in males. By day 50-55 both sexes attained adult enzyme levels. STII was the major enzyme in all immature animals. STIII was also present, but STI was absent. In male rats STIII activity began to rise by day 30. Soon after, STII activity began to drop. By day 55 adult male patterns developed. STI was the major enzyme in females by day 30. In ensuing days all 3 enzyme levels rose, until by day 50 adult enzyme patterns and levels were attained. The data suggest that the ovaries stimulated production of all 3 sulfotransferases and that the testes suppressed production of STII (and perhaps STI). Preliminary studies with gonadectomized rats supported the suppressive role of the testes, but suggested that the ovaries were not the only factor controlling sulfotransferase production in female rats."} {"id": "PMID:1278102", "title": "Sex differences in the effects of surgical isolation of the medial basal hypothalamus on linear growth and plasma growth hormone levels in the rat.", "content": "The effects of surgical isolation of the medial basal hypothalamus (MBH) on linear growth and plasma growth hormone (GH) levels were studied in adult male and female rats. Whereas MBH isolation resulted in reduced linear growth in males, increased growth resulted in females. These effects were apparent in males 4 weeks after surgery and in females at 10 weeks. The altered growth rates persisted throughout the 28 weeks of the study. MBH isolation in both sexes led to increased food intake, obesity, and atrophy of reproductive tract organs. Non-stress plasma GH levels were unchanged at 4 weeks in both sexes but were elevated at 10 and 26 weeks in females and at 19 and 26 weeks in males. Serial samples of tail vein blood were obtained at 4-h intervals for 44 h from MBH-isolated and shamoperated females at 17 weeks postoperatively, and from similar groups of males at 19 weeks. GH levels were elevated in MBH-isolated rats of both sexes during the afternoons and evenings. Only sham-operated females showed evidence of a 24-h rhythmicity in circulating GH levels. The amplitudes of trough to peak excursions were similar in MBH-isolated and control females, but these excursions were reduced in MBH-isolated males. Although opposite effects on linear growth were noted in the two sexes, the resulting growth rates of operated males and females were similar, suggesting that MBH isolation disrupts mechanisms that normally regulate sex-specific growth patterns. Despite the sex difference in growth responses, MBH isolation caused an eventual increase in plasma GH levels in both sexes. Therefore, it is unlikely that the sex difference in growth responses is attributable exclusively to corresponding changes in circulating GH levels. A reduction in levels of circulating gonadal steroids may be an important factor. The elevations in plasma GH levels observed in both sexes suggest that MBH isolation interferes with mechanisms which inhibit GH secretion.", "contents": "Sex differences in the effects of surgical isolation of the medial basal hypothalamus on linear growth and plasma growth hormone levels in the rat. The effects of surgical isolation of the medial basal hypothalamus (MBH) on linear growth and plasma growth hormone (GH) levels were studied in adult male and female rats. Whereas MBH isolation resulted in reduced linear growth in males, increased growth resulted in females. These effects were apparent in males 4 weeks after surgery and in females at 10 weeks. The altered growth rates persisted throughout the 28 weeks of the study. MBH isolation in both sexes led to increased food intake, obesity, and atrophy of reproductive tract organs. Non-stress plasma GH levels were unchanged at 4 weeks in both sexes but were elevated at 10 and 26 weeks in females and at 19 and 26 weeks in males. Serial samples of tail vein blood were obtained at 4-h intervals for 44 h from MBH-isolated and shamoperated females at 17 weeks postoperatively, and from similar groups of males at 19 weeks. GH levels were elevated in MBH-isolated rats of both sexes during the afternoons and evenings. Only sham-operated females showed evidence of a 24-h rhythmicity in circulating GH levels. The amplitudes of trough to peak excursions were similar in MBH-isolated and control females, but these excursions were reduced in MBH-isolated males. Although opposite effects on linear growth were noted in the two sexes, the resulting growth rates of operated males and females were similar, suggesting that MBH isolation disrupts mechanisms that normally regulate sex-specific growth patterns. Despite the sex difference in growth responses, MBH isolation caused an eventual increase in plasma GH levels in both sexes. Therefore, it is unlikely that the sex difference in growth responses is attributable exclusively to corresponding changes in circulating GH levels. A reduction in levels of circulating gonadal steroids may be an important factor. The elevations in plasma GH levels observed in both sexes suggest that MBH isolation interferes with mechanisms which inhibit GH secretion."} {"id": "PMID:1278103", "title": "Pulsatile growth hormone release in the rat: failure to demonstrate a correlation with sleep phases.", "content": "Concurrent 5-hour profiles of growth hormone (GH) secretion and sleep phases were obtained in 7 rats chronically implanted with right atrial cannulae, and electroencephalographic electromyographic, and electroculographic electrodes. Hormone profiles confirmed pulsatile secretion of GH. Secretory GH episodes occurred every 3 to 4 hours and peaks generally exceeded 100 ng/ml, and, in 14 of the 21 troughs recorded, GH was unmeasurable (less than 1 ng/ml). The comparison of hormone profiles and concurrent sleep patterns excluded a temporal relationship between episodic GH secretion and sleep cycles, while scattergrams of hormone values plotted against preceding sleep phase durations also failed to demonstrate a relationship.", "contents": "Pulsatile growth hormone release in the rat: failure to demonstrate a correlation with sleep phases. Concurrent 5-hour profiles of growth hormone (GH) secretion and sleep phases were obtained in 7 rats chronically implanted with right atrial cannulae, and electroencephalographic electromyographic, and electroculographic electrodes. Hormone profiles confirmed pulsatile secretion of GH. Secretory GH episodes occurred every 3 to 4 hours and peaks generally exceeded 100 ng/ml, and, in 14 of the 21 troughs recorded, GH was unmeasurable (less than 1 ng/ml). The comparison of hormone profiles and concurrent sleep patterns excluded a temporal relationship between episodic GH secretion and sleep cycles, while scattergrams of hormone values plotted against preceding sleep phase durations also failed to demonstrate a relationship."} {"id": "PMID:1278104", "title": "Selective suppression of FSH by testicular extracts.", "content": "Studies were undertaken to determine the effects of intravenous infusions of bovine testicular extracts on plasma levels of FSH and LH in castrate male sheep. Decapsulated bovine testes were homogenized with phosphate buffer, the homogenates centrifuged at 30,000 X g for 30 min, and the supernatants extracted with diethyl ether. The aqueous extracts were filtered using Diaflo XM-100 membranes and the ultra-filtrates lyophilized. The extracts were infused over 24 hours, and plasma FSH and LH were measured prior to, during, and after the infusion. Control studies using infusions of saline and liver extracts demonstrated no decrease in FSH levels in 6 out of 7 controls, while LH levels tended to rise. Following infusions with the testicular extracts, the levels of FSH were selectively decreased to between 42% and 85% of baseline levels, and they subsequently remained suppressed for at least 24 hours. These results suggest that the testis is the site of production of a water-soluble, non-steroidal substance which exerts an inhibitory effect on the production and/or release of FSH.", "contents": "Selective suppression of FSH by testicular extracts. Studies were undertaken to determine the effects of intravenous infusions of bovine testicular extracts on plasma levels of FSH and LH in castrate male sheep. Decapsulated bovine testes were homogenized with phosphate buffer, the homogenates centrifuged at 30,000 X g for 30 min, and the supernatants extracted with diethyl ether. The aqueous extracts were filtered using Diaflo XM-100 membranes and the ultra-filtrates lyophilized. The extracts were infused over 24 hours, and plasma FSH and LH were measured prior to, during, and after the infusion. Control studies using infusions of saline and liver extracts demonstrated no decrease in FSH levels in 6 out of 7 controls, while LH levels tended to rise. Following infusions with the testicular extracts, the levels of FSH were selectively decreased to between 42% and 85% of baseline levels, and they subsequently remained suppressed for at least 24 hours. These results suggest that the testis is the site of production of a water-soluble, non-steroidal substance which exerts an inhibitory effect on the production and/or release of FSH."} {"id": "PMID:1278105", "title": "Influence of sodium intake on vascular and adrenal angiotensin II receptors.", "content": "The restriction of sodium intake reduces the sensitivity of vascular smooth muscle to angiotensin II, but enhances its influence on the adrenal glomerulosa cell. A competitive antagonist to angiotensin II, the Sar1, Ala8 derivative (P113), which shows affinity for the same receptor as angiotensin II, was used to examine the role of receptor affinity in the effect of sodium intake on these two systems in vitro. A threshold P113 concentration reduced the response to angiotensin of aortas derived from rabbits on a high, but not on a low, salt intake. Similarly, a threshold P113 concentration inhibited aldosterone response to angiotensin in glomerulosa cells obtained from sodium-loaded, but not sodium-restricted, rats. Large doses of P113 reduced the response to angiotensin in both preparations on either diet. The competitive antagonist presumably shares affinity for the same receptor on the basis of structural similarities; thus, the results suggest that sodium restriction blunts the vasoactive effects of angiotensin by reducing the affinity of its receptor for angiotensin. In contrast, the enhanced adrenal response to angiotensin with sodium restriction cannot be explained by an altered receptor-agonist interaction, but must reside in a change in an intracellular biochemical process, sufficient to overcome the influence of reduced receptor affinity.", "contents": "Influence of sodium intake on vascular and adrenal angiotensin II receptors. The restriction of sodium intake reduces the sensitivity of vascular smooth muscle to angiotensin II, but enhances its influence on the adrenal glomerulosa cell. A competitive antagonist to angiotensin II, the Sar1, Ala8 derivative (P113), which shows affinity for the same receptor as angiotensin II, was used to examine the role of receptor affinity in the effect of sodium intake on these two systems in vitro. A threshold P113 concentration reduced the response to angiotensin of aortas derived from rabbits on a high, but not on a low, salt intake. Similarly, a threshold P113 concentration inhibited aldosterone response to angiotensin in glomerulosa cells obtained from sodium-loaded, but not sodium-restricted, rats. Large doses of P113 reduced the response to angiotensin in both preparations on either diet. The competitive antagonist presumably shares affinity for the same receptor on the basis of structural similarities; thus, the results suggest that sodium restriction blunts the vasoactive effects of angiotensin by reducing the affinity of its receptor for angiotensin. In contrast, the enhanced adrenal response to angiotensin with sodium restriction cannot be explained by an altered receptor-agonist interaction, but must reside in a change in an intracellular biochemical process, sufficient to overcome the influence of reduced receptor affinity."} {"id": "PMID:1278106", "title": "Reproductive hormonal function in the genetically obese (ob/ob) mouse.", "content": "Reproductive function is impaired in the genetically obese (C57 B1/6J) ob/ob mouse. Serum LH, FSH, and testosterone concentrations were assessed in male ob/ob and lean littermates from 39 to 78 days of age. The lean animals demonstrated a three-fold rise in serum LH between 39 and 45 days of age that preceded a steep increase in serum testosterone which peaked at age 70 days. The obese animals did not demonstrate this LH rise; serum testosterone levels were low and had a blunted increase with age that paralleled that of normal animals. Serum FSH was lower than normal at all ages in the obese mice. The ventral prostrate and testes were small in the ob/ob mice. The castration of adult animals resulted in increased serum concentrations of both LH and FSH, with higher levels attained in the lean animals. Fifty-four-day-old castrated lean and obese mice were treated with testosterone for 15 days. Measurements of serum LH and FSH after 8 and 15 days of treatment demonstrated a marked sensitivity in the ob/ob animals to feedback inhibition of gonadotropins. This finding suggested persistent immaturity of the hypothalamic-pituitary axis in obese mice. These studies indicate that the hypogonadism of the ob/ob mouse is the result of altered hypothalamic-pituitary function.", "contents": "Reproductive hormonal function in the genetically obese (ob/ob) mouse. Reproductive function is impaired in the genetically obese (C57 B1/6J) ob/ob mouse. Serum LH, FSH, and testosterone concentrations were assessed in male ob/ob and lean littermates from 39 to 78 days of age. The lean animals demonstrated a three-fold rise in serum LH between 39 and 45 days of age that preceded a steep increase in serum testosterone which peaked at age 70 days. The obese animals did not demonstrate this LH rise; serum testosterone levels were low and had a blunted increase with age that paralleled that of normal animals. Serum FSH was lower than normal at all ages in the obese mice. The ventral prostrate and testes were small in the ob/ob mice. The castration of adult animals resulted in increased serum concentrations of both LH and FSH, with higher levels attained in the lean animals. Fifty-four-day-old castrated lean and obese mice were treated with testosterone for 15 days. Measurements of serum LH and FSH after 8 and 15 days of treatment demonstrated a marked sensitivity in the ob/ob animals to feedback inhibition of gonadotropins. This finding suggested persistent immaturity of the hypothalamic-pituitary axis in obese mice. These studies indicate that the hypogonadism of the ob/ob mouse is the result of altered hypothalamic-pituitary function."} {"id": "PMID:1278107", "title": "Secretion cells in the gastrointestinal tract.", "content": "The morphology and distribution of secretin (S) cells were investigated in the human and the dog. S cells were well-visualized by the indired immunofluorescence antibody technique, using a highly specific rabbit anti-secretin sera. The fluorescence reaction was not blocked by an excess amount of gastrin, cholecystokinin, glucagon, vasoactive intestinal polypeptide, or motilin, whereas secretin blocked the reaction. S cells were seen in the mucosa of the antrum and duodenum in both humans and dogs, and throughout the entire length of the canine small intestine. They were not found in the mucosa of the esophagus, fundus of the stomach, or rectum. These cells were either pyramidal in shape or pearshaped and were one-third of the size of gastrin cells. The possible significance of S-cell distribution in the antrum and small intestine is discussed.", "contents": "Secretion cells in the gastrointestinal tract. The morphology and distribution of secretin (S) cells were investigated in the human and the dog. S cells were well-visualized by the indired immunofluorescence antibody technique, using a highly specific rabbit anti-secretin sera. The fluorescence reaction was not blocked by an excess amount of gastrin, cholecystokinin, glucagon, vasoactive intestinal polypeptide, or motilin, whereas secretin blocked the reaction. S cells were seen in the mucosa of the antrum and duodenum in both humans and dogs, and throughout the entire length of the canine small intestine. They were not found in the mucosa of the esophagus, fundus of the stomach, or rectum. These cells were either pyramidal in shape or pearshaped and were one-third of the size of gastrin cells. The possible significance of S-cell distribution in the antrum and small intestine is discussed."} {"id": "PMID:1278108", "title": "Further study of the mechanism of thyroid hormone secretion in an in vitro model system: direct evidence for fusion of lysosomes with thyroglobulin liposomes.", "content": "The interaction between thyroglobulin liposomes, as a model of colloid droplets, and thyroidal lysosomes was studied in an in vitro system. On sucrose density gradient centrifugation analysis, particulate lysosomes were distributed in a high density region and were apparently clearly separated from the liposomal peak. However, when the liposomes and lysosomes were incubated together and then analyzed, the liposomes were found to migrate with the lysosomal peak. The extent of this translocation of liposomes depended on the incubation temperature: after incubations at 37 C and 0 C, 56% and 35%, respectively, of the radioactivity of liposomes was found in the lysosomal peak. This phenomenon was inhibited by 50% in the presence of 10(-3)M chlorpromazine. Matrix-labeled liposomes [125I]thyroglobulin liposomes), and membrane labeled lipolomes ([14C]-cholesterol-labeled thyroglobulin liposomes) showed similar distribution patterns in the lysosomal peak on gradient centrifugation. The liposomal thyroglobulin was hydrolyzed in a time-dependent manner in the fraction showing both radioactivity and acid phosphatase activity. These results provide direct evidence of liposome-lysosome fusion, or formation of phagolysosomes.", "contents": "Further study of the mechanism of thyroid hormone secretion in an in vitro model system: direct evidence for fusion of lysosomes with thyroglobulin liposomes. The interaction between thyroglobulin liposomes, as a model of colloid droplets, and thyroidal lysosomes was studied in an in vitro system. On sucrose density gradient centrifugation analysis, particulate lysosomes were distributed in a high density region and were apparently clearly separated from the liposomal peak. However, when the liposomes and lysosomes were incubated together and then analyzed, the liposomes were found to migrate with the lysosomal peak. The extent of this translocation of liposomes depended on the incubation temperature: after incubations at 37 C and 0 C, 56% and 35%, respectively, of the radioactivity of liposomes was found in the lysosomal peak. This phenomenon was inhibited by 50% in the presence of 10(-3)M chlorpromazine. Matrix-labeled liposomes [125I]thyroglobulin liposomes), and membrane labeled lipolomes ([14C]-cholesterol-labeled thyroglobulin liposomes) showed similar distribution patterns in the lysosomal peak on gradient centrifugation. The liposomal thyroglobulin was hydrolyzed in a time-dependent manner in the fraction showing both radioactivity and acid phosphatase activity. These results provide direct evidence of liposome-lysosome fusion, or formation of phagolysosomes."} {"id": "PMID:1278109", "title": "Oxytocin content of microdissected areas of rat hypothalamus.", "content": "Oxytocin content has been measured by radioimmunoassay in microdissected hypothalamic nuclei. Equal concentrations of oxytocin were found in the supraoptic and the paraventricular nuclei, indicating that both are major sources of the hormone. The concentration of oxytocin in the median eminence was more than three times that in either the supraoptic or the paraventricular nuclei, and significant amounts of oxytocin were also found in the arcuate nucleus and in tow anterior hypothalamic nuclei.", "contents": "Oxytocin content of microdissected areas of rat hypothalamus. Oxytocin content has been measured by radioimmunoassay in microdissected hypothalamic nuclei. Equal concentrations of oxytocin were found in the supraoptic and the paraventricular nuclei, indicating that both are major sources of the hormone. The concentration of oxytocin in the median eminence was more than three times that in either the supraoptic or the paraventricular nuclei, and significant amounts of oxytocin were also found in the arcuate nucleus and in tow anterior hypothalamic nuclei."} {"id": "PMID:1278110", "title": "Postnatal development of mouse plasma and brain corticosterone levels: new findings contingent upon the use of a competitive protein-binding assay.", "content": "A competitive protein-binding (CPB) assay, suitable for measuring corticosterone levels in 20 mul of mouse plasma or 100 mg of brain, is described. The postnatal development of adrenocortical function was determined in C57BL/10 and DBA/1 mice by CPB assay of basal and stressinduced levels of plasma corticosterone and resting levels of brain corticosterone. Marked increases in both basal and stressed levels of plasma corticosterone were found beginning at day 12 after birth: mean basal levels rose from about 1 mug/u99 ml on day 12 to peak values of about 10-15 mug/100 ml on days 18-20, and then declined by day 30 to the 13-day level of 2.6 mug/100 ml. This pattern differs significantly from results obtained with standard fluorometric assays for corticosterone; it was determined that a major part of this discrepancy is due to the lack of specificity of the fluorometric assay. The developmental change in brain corticosterone was similar to the pattern found in plasma. Only the stress-induced levels of plasma corticosterone showed significant genetic variation, and this did not appear until about one week after the end of the relative stress-nonresponsive period. These findings should be useful in evaluating hypotheses concerning the developmental regulation of adrenocortical function and the action of glucocorticoids in regulating the biochemical differentiation of other tissues.", "contents": "Postnatal development of mouse plasma and brain corticosterone levels: new findings contingent upon the use of a competitive protein-binding assay. A competitive protein-binding (CPB) assay, suitable for measuring corticosterone levels in 20 mul of mouse plasma or 100 mg of brain, is described. The postnatal development of adrenocortical function was determined in C57BL/10 and DBA/1 mice by CPB assay of basal and stressinduced levels of plasma corticosterone and resting levels of brain corticosterone. Marked increases in both basal and stressed levels of plasma corticosterone were found beginning at day 12 after birth: mean basal levels rose from about 1 mug/u99 ml on day 12 to peak values of about 10-15 mug/100 ml on days 18-20, and then declined by day 30 to the 13-day level of 2.6 mug/100 ml. This pattern differs significantly from results obtained with standard fluorometric assays for corticosterone; it was determined that a major part of this discrepancy is due to the lack of specificity of the fluorometric assay. The developmental change in brain corticosterone was similar to the pattern found in plasma. Only the stress-induced levels of plasma corticosterone showed significant genetic variation, and this did not appear until about one week after the end of the relative stress-nonresponsive period. These findings should be useful in evaluating hypotheses concerning the developmental regulation of adrenocortical function and the action of glucocorticoids in regulating the biochemical differentiation of other tissues."} {"id": "PMID:1278111", "title": "A model system for studying inhibin.", "content": "We report here a sensitive model for studying inhibin-like activity in crude ovine testicular extracts (CoTE). The administration of CoTE in 25-100 mg amounts to 35-day-old immature male rats, orchidectomized just prior to use, resulted in the prevention of a rise in plasma FSH levels, seen 10 h post-treatment. In a second model, CoTE was injected at 1000 h of day 35 to a group of rats that was castrated 12-24 h prior to injection, and the animals were sacrificed 6 h later; plasma FSH levels were found to be significantly suppressed. CoTE, administered subcutaneously, both in multiple doses and as a single injection, was found to be equally effective. A single injection suppressed FSH levels within 3-6 h while LH levels were unaffected. The suppressive effect was dose-dependent, reaching a maximum value at doses of 100 mg CoTE and above. FSH levels could not be suppressed below the tonic level, either by the administration of a single large dose of CoTE, or by repetitive injections of maximal doses of CoTE at 3 h intervals. The suppression in FSH levels caused by a single injection of CoTE waned with time and totally disappeared by 36h. CoTE was prepared by the heat treatment (55 C for 30 min) of an aqueous extract of ovine testis, followed by centrifugation and ether extraction of the supernatant. The aqueous layer was then dialyzed and lyophilized. The lyophilized material was found to be free of testosterone, as measured by a specific radioimmunoassay, indicating that the active factor is a heat-stable, lyophilizable, nondialyzable material, free of contamination by testosterone and probably by other steroids.", "contents": "A model system for studying inhibin. We report here a sensitive model for studying inhibin-like activity in crude ovine testicular extracts (CoTE). The administration of CoTE in 25-100 mg amounts to 35-day-old immature male rats, orchidectomized just prior to use, resulted in the prevention of a rise in plasma FSH levels, seen 10 h post-treatment. In a second model, CoTE was injected at 1000 h of day 35 to a group of rats that was castrated 12-24 h prior to injection, and the animals were sacrificed 6 h later; plasma FSH levels were found to be significantly suppressed. CoTE, administered subcutaneously, both in multiple doses and as a single injection, was found to be equally effective. A single injection suppressed FSH levels within 3-6 h while LH levels were unaffected. The suppressive effect was dose-dependent, reaching a maximum value at doses of 100 mg CoTE and above. FSH levels could not be suppressed below the tonic level, either by the administration of a single large dose of CoTE, or by repetitive injections of maximal doses of CoTE at 3 h intervals. The suppression in FSH levels caused by a single injection of CoTE waned with time and totally disappeared by 36h. CoTE was prepared by the heat treatment (55 C for 30 min) of an aqueous extract of ovine testis, followed by centrifugation and ether extraction of the supernatant. The aqueous layer was then dialyzed and lyophilized. The lyophilized material was found to be free of testosterone, as measured by a specific radioimmunoassay, indicating that the active factor is a heat-stable, lyophilizable, nondialyzable material, free of contamination by testosterone and probably by other steroids."} {"id": "PMID:1278112", "title": "Isolation of renin granules from rat kidney cortex and evidence for an inactive form of renin (prorenin) in granules and plasma.", "content": "Renin was demonstrated in particles having a sedimentation velocity similar to that of mitochondria during differential centrifugation separated renin granules from the bulk of mitochondria and lyosomes, as well as from microsomes and cytoplasm. The density of renin granules was 1.202, which differed from the mean equilibrium densities of mitochondria (1.175) and lysosomes (1.170 and 1.230) in the heavy granule fraction. In studies involving gel filtration and polyacrylamide gel electrophoreis, renin granules appeared to contain an inactive form of renin that could be activated by acid treatment, had a higher apparent molecular weight than renin, and may be a more basic molecule. Inactive renin was also studied in plasma by electrophoresis and may originate from renin granules after exocytosis by the juxtaglomerular cells. Inactive renin may be a biosynthetic precursor (prorenin) and may be activated within the cell by a specific protease consequent upon the fusion of renin granules with lysosomes, thus providing a mechanism for the rapid regulation of renin activity prior to secretion.", "contents": "Isolation of renin granules from rat kidney cortex and evidence for an inactive form of renin (prorenin) in granules and plasma. Renin was demonstrated in particles having a sedimentation velocity similar to that of mitochondria during differential centrifugation separated renin granules from the bulk of mitochondria and lyosomes, as well as from microsomes and cytoplasm. The density of renin granules was 1.202, which differed from the mean equilibrium densities of mitochondria (1.175) and lysosomes (1.170 and 1.230) in the heavy granule fraction. In studies involving gel filtration and polyacrylamide gel electrophoreis, renin granules appeared to contain an inactive form of renin that could be activated by acid treatment, had a higher apparent molecular weight than renin, and may be a more basic molecule. Inactive renin was also studied in plasma by electrophoresis and may originate from renin granules after exocytosis by the juxtaglomerular cells. Inactive renin may be a biosynthetic precursor (prorenin) and may be activated within the cell by a specific protease consequent upon the fusion of renin granules with lysosomes, thus providing a mechanism for the rapid regulation of renin activity prior to secretion."} {"id": "PMID:1278113", "title": "Hepatic glucocorticoid binders in mature and senescent C57BL/6J male mice.", "content": "Because of prominent age-related changes in the responses to stress and in steroid metabolism and excretion, the effect of age on fractionated liver glucocorticoid-binding proteins was studied in C57BL/6J male mice. When cytosol, pre-labeled with [3H]corticosterone, was chromatographed on Sephadex G-100, 4 peaks were obtained. Peak 1 (excluded), peak 2 (corresponding to plasma transcortin), and peak 3 corresponding to glucocorticoid receptors isolated from nuclei) showed no significant age differences. This finding is consistent with reports that glucocorticoid-mediated induction of hepatic tyrosine aminotransferase is not altered by aging in rodents. However, there was a striking age-related decrease (80%) in peak 4 (apparent MW 29,000). Competition studies imply that peak 4 binds aldosterone, testosterone, progesterone, and corticosterone (delta4-3-keto steroids), but not estradiol or dt a plasma component. Although the function of peak 4 is not identified, the pattern of highest competition with delta4-3-keto steroids suggests that it is a steroid ring \"A\" reductase.", "contents": "Hepatic glucocorticoid binders in mature and senescent C57BL/6J male mice. Because of prominent age-related changes in the responses to stress and in steroid metabolism and excretion, the effect of age on fractionated liver glucocorticoid-binding proteins was studied in C57BL/6J male mice. When cytosol, pre-labeled with [3H]corticosterone, was chromatographed on Sephadex G-100, 4 peaks were obtained. Peak 1 (excluded), peak 2 (corresponding to plasma transcortin), and peak 3 corresponding to glucocorticoid receptors isolated from nuclei) showed no significant age differences. This finding is consistent with reports that glucocorticoid-mediated induction of hepatic tyrosine aminotransferase is not altered by aging in rodents. However, there was a striking age-related decrease (80%) in peak 4 (apparent MW 29,000). Competition studies imply that peak 4 binds aldosterone, testosterone, progesterone, and corticosterone (delta4-3-keto steroids), but not estradiol or dt a plasma component. Although the function of peak 4 is not identified, the pattern of highest competition with delta4-3-keto steroids suggests that it is a steroid ring \"A\" reductase."} {"id": "PMID:1278114", "title": "A sensitive radioenzymatic assay for dopamine, norepinephrine, and epinephrine in plasma and tissue.", "content": "A double-isotope, radioenzymatic assay for measuring dopamine, norepinephrine, and epinephrine in one sample is described. The assay procedure includes incubation, solvent extraction, and thin-layer chromatography. Dopamine, norepinephrine, and epinephrine were incubated with catechol-O-methyl transferase (COMT) and [3H]S-acenosyl methionine ([3H]SAM) and were converted to the O-methylated tritiated derivatives: [3H]methoxytyramine, [3H]normetanephrine, and [3H]metanephrine, respectively. After several extraction steps the O-methylated products were purified by means of two-dimensional, thin-layer chromatography using silica gel. The thin-layer chromatographic system resulted complete separation of the three O-methylated compounds with an overlap of only 1-2%. The assay was linear from 0 to 5 ng for each catecholamine and had a sensitivity of 10-30 pg. The addition of large amounts of plasma reduced the activity of COMT, but increasing the magnesium concentration in the incubation mixture and the addition of EGTA to plasma samples improved the recoveries. Each sample was corrected for losses incurred during extraction and chromatography by using [14C]methoxytyramine, [14C]normetanephrine, and [14Ci1metanephrine that were added at the end of incubation. Several catechol compounds known to be O-methylated by COMT were examined for crossreactivity. Of the substances tested, only dihydroxyphenylalanine (DOPA) exhibited cross-reactivity. However, the apparent 30% cross-reactivity of DOPA with dopamine was due to the presence of decarboxylase activity in the COMT preparation. As little as 50 mul of trunk plasma from decapitated rats was sufficient for the determination of the three catecholamines.", "contents": "A sensitive radioenzymatic assay for dopamine, norepinephrine, and epinephrine in plasma and tissue. A double-isotope, radioenzymatic assay for measuring dopamine, norepinephrine, and epinephrine in one sample is described. The assay procedure includes incubation, solvent extraction, and thin-layer chromatography. Dopamine, norepinephrine, and epinephrine were incubated with catechol-O-methyl transferase (COMT) and [3H]S-acenosyl methionine ([3H]SAM) and were converted to the O-methylated tritiated derivatives: [3H]methoxytyramine, [3H]normetanephrine, and [3H]metanephrine, respectively. After several extraction steps the O-methylated products were purified by means of two-dimensional, thin-layer chromatography using silica gel. The thin-layer chromatographic system resulted complete separation of the three O-methylated compounds with an overlap of only 1-2%. The assay was linear from 0 to 5 ng for each catecholamine and had a sensitivity of 10-30 pg. The addition of large amounts of plasma reduced the activity of COMT, but increasing the magnesium concentration in the incubation mixture and the addition of EGTA to plasma samples improved the recoveries. Each sample was corrected for losses incurred during extraction and chromatography by using [14C]methoxytyramine, [14C]normetanephrine, and [14Ci1metanephrine that were added at the end of incubation. Several catechol compounds known to be O-methylated by COMT were examined for crossreactivity. Of the substances tested, only dihydroxyphenylalanine (DOPA) exhibited cross-reactivity. However, the apparent 30% cross-reactivity of DOPA with dopamine was due to the presence of decarboxylase activity in the COMT preparation. As little as 50 mul of trunk plasma from decapitated rats was sufficient for the determination of the three catecholamines."} {"id": "PMID:1278115", "title": "Medroxyprogesterone acetate: a steroid with potent progestational activity but low receptor affinity in the guinea pig uterus.", "content": "The guinea pig progestin receptor appears to be unique among mammalian receptors studied to date in that it displays a low binding affinity for some biologically potent 17 alpha-substituted progestinss. [3H]Medroxyprogesterone acetate (MPA) was synthesized and used to investigate this dichotomy between binding affinity and biological activity. The comparison of cytoplasmic and nuclear receptor binding characteristics suggested that progesterone and MPA were bound to the same receptor but with different affinities. Following an intravenous injection of 3H-steroids, the plasma level of progesterone was lower than that of MPA at all time points. Correspondingly, for up to 6 hours following steroid administration, progesterone levels were lower in uterine cytoplasm and higher in nuclei than those of MPA. However, by 24 hours, MPA nuclear levels were higher than those of progesterone, in accordance with plasma levels. We conclude that the potent biological activity of MPA relative to progesterone is due in part to its slower rate of metabolism and longer nuclear retention.", "contents": "Medroxyprogesterone acetate: a steroid with potent progestational activity but low receptor affinity in the guinea pig uterus. The guinea pig progestin receptor appears to be unique among mammalian receptors studied to date in that it displays a low binding affinity for some biologically potent 17 alpha-substituted progestinss. [3H]Medroxyprogesterone acetate (MPA) was synthesized and used to investigate this dichotomy between binding affinity and biological activity. The comparison of cytoplasmic and nuclear receptor binding characteristics suggested that progesterone and MPA were bound to the same receptor but with different affinities. Following an intravenous injection of 3H-steroids, the plasma level of progesterone was lower than that of MPA at all time points. Correspondingly, for up to 6 hours following steroid administration, progesterone levels were lower in uterine cytoplasm and higher in nuclei than those of MPA. However, by 24 hours, MPA nuclear levels were higher than those of progesterone, in accordance with plasma levels. We conclude that the potent biological activity of MPA relative to progesterone is due in part to its slower rate of metabolism and longer nuclear retention."} {"id": "PMID:1278116", "title": "Effect of sexual maturation and androgens on prostaglandin levels in tissues of the male reproductive system in mice.", "content": "Prostaglandins E and F were measured in the testis, epididymis, vas deferens, and seminal vesicles of CD-1 mice from 2 to 8 weeks of age. The concentration of PGF was higher than that of PGE in all organs studied, except for the vas deferens. The concentration of prostaglandins (PGs) was age-dependent, showing a progressive decline from immaturity to adulthood. However, in the testis, there was an apparent transient increase in the concentration of PGs in the seminal vesicle changed very little between the ages of 5 and 8 weeks. The vas deferens had a significantly higher PG concentration than any of the organs studied, and a unique pattern of changes in the levels of PGE and PGF with age. In the vas deferens of two- and three-week-old mice, the concentration of PGF was higher than the concentration of PGE, but after 4 weeks of age PGE became somewhat more abundant than PGF. Treatment of immature mice with testosterone propionate (TP) produced significant changes in PG concentrations, resulting in PG levels resembling those of adult animals. The treatment also changed the ratio of PGE to PGF in the vas deferens (from 1:2 to 1:1). Hereditary dwarf mice had higher levels of PGs in the tissues of the male reproductive system than did their normal littermates. The treatment of dwarf mice with TP generally reduced the concentration of PGs in their reproductive system and resulted in a PG pattern more characteristic of normal adult males of the same strain. The data demonstrate pronounced changes in PG levels in the tissues of the male reporductive system of mice during sexual maturation. From the present study and from previous findings, it can be concluded that these changes can be accounted for by an increase in testicular testosterone secretion.", "contents": "Effect of sexual maturation and androgens on prostaglandin levels in tissues of the male reproductive system in mice. Prostaglandins E and F were measured in the testis, epididymis, vas deferens, and seminal vesicles of CD-1 mice from 2 to 8 weeks of age. The concentration of PGF was higher than that of PGE in all organs studied, except for the vas deferens. The concentration of prostaglandins (PGs) was age-dependent, showing a progressive decline from immaturity to adulthood. However, in the testis, there was an apparent transient increase in the concentration of PGs in the seminal vesicle changed very little between the ages of 5 and 8 weeks. The vas deferens had a significantly higher PG concentration than any of the organs studied, and a unique pattern of changes in the levels of PGE and PGF with age. In the vas deferens of two- and three-week-old mice, the concentration of PGF was higher than the concentration of PGE, but after 4 weeks of age PGE became somewhat more abundant than PGF. Treatment of immature mice with testosterone propionate (TP) produced significant changes in PG concentrations, resulting in PG levels resembling those of adult animals. The treatment also changed the ratio of PGE to PGF in the vas deferens (from 1:2 to 1:1). Hereditary dwarf mice had higher levels of PGs in the tissues of the male reproductive system than did their normal littermates. The treatment of dwarf mice with TP generally reduced the concentration of PGs in their reproductive system and resulted in a PG pattern more characteristic of normal adult males of the same strain. The data demonstrate pronounced changes in PG levels in the tissues of the male reporductive system of mice during sexual maturation. From the present study and from previous findings, it can be concluded that these changes can be accounted for by an increase in testicular testosterone secretion."} {"id": "PMID:1278117", "title": "Content of LH, FSH, and growth hormone in the pituitaries of pregnant and anestrous sheep.", "content": "The total content of LH, FSH, and growth hormone was measured in pituitaries from anestrous ewes and from ewes at known stages of pregnancy. LH content was lower in the pregnant ewes than in the anestrous group. Compared with the anestrous group, a significant drop in mean LH content was seen by days 40-50 of pregnancy (894 vs 350 mug, P less than 0.001), and it reached its lowest value by 120-135 days of pregnancy (43 mug, P less than 0.001). In sheep 148 days of pregnant, mean LH content was higher than in the latter group (155 mug). The correlation coefficient between the stage of gestation and the LH content was 0.63 (P less than 0.01). There was no significant change in mean FSH content in ewes up to 135 days pregnant (range 1196-1550 mug) compared with anestrous ewes (1023 mug). In the group 148 days pregnant (531 mug), a significant decrease was seen compared with ewes at other stages of pregnancy (P less than 0.05). Stage of gestation and FSH content were poorly correlated (r = 0.07). No significant differences in growth hormone content were seen in any of the groups. The results suggest that the progressive reduction in LH response to synthetic GnRH which has been reported for pregnant sheep may be due to selective inhibition of LH biosynthesis.", "contents": "Content of LH, FSH, and growth hormone in the pituitaries of pregnant and anestrous sheep. The total content of LH, FSH, and growth hormone was measured in pituitaries from anestrous ewes and from ewes at known stages of pregnancy. LH content was lower in the pregnant ewes than in the anestrous group. Compared with the anestrous group, a significant drop in mean LH content was seen by days 40-50 of pregnancy (894 vs 350 mug, P less than 0.001), and it reached its lowest value by 120-135 days of pregnancy (43 mug, P less than 0.001). In sheep 148 days of pregnant, mean LH content was higher than in the latter group (155 mug). The correlation coefficient between the stage of gestation and the LH content was 0.63 (P less than 0.01). There was no significant change in mean FSH content in ewes up to 135 days pregnant (range 1196-1550 mug) compared with anestrous ewes (1023 mug). In the group 148 days pregnant (531 mug), a significant decrease was seen compared with ewes at other stages of pregnancy (P less than 0.05). Stage of gestation and FSH content were poorly correlated (r = 0.07). No significant differences in growth hormone content were seen in any of the groups. The results suggest that the progressive reduction in LH response to synthetic GnRH which has been reported for pregnant sheep may be due to selective inhibition of LH biosynthesis."} {"id": "PMID:1278118", "title": "A fast in vitro effect of glucocorticoids on hepatic lipolysis.", "content": "A fast and direct effect of dexamethasone on liver metabolism is reported. In the perfused rat liver, addition of dexamethasone directly to the perfusate is followed by an increase in the level of free fatty acids (FFA) and glycerol. These effects of dexamethasone are evident within 30 minutes of hormone administration. The response to dexamethasone in livers from normal and adrenalectomized rats is similar. While dexamethasone and glucagon both had a lipolytic effect, these effects are not additive.", "contents": "A fast in vitro effect of glucocorticoids on hepatic lipolysis. A fast and direct effect of dexamethasone on liver metabolism is reported. In the perfused rat liver, addition of dexamethasone directly to the perfusate is followed by an increase in the level of free fatty acids (FFA) and glycerol. These effects of dexamethasone are evident within 30 minutes of hormone administration. The response to dexamethasone in livers from normal and adrenalectomized rats is similar. While dexamethasone and glucagon both had a lipolytic effect, these effects are not additive."} {"id": "PMID:1278119", "title": "Effects of microinjection of various prostaglandins into the 3rd ventricle, median eminence and pituitary on plasma LH in rats.", "content": "The effects of microinjection of PG'S (PGE1, E2, F2a) into the 3rd ventricle, median eminence (ME) and anterior pituitary on plasma LH in rats were investigated. Blood samples were obtained by jugular puncture before, and 10 and 45 min after the injection of PGS (50 or 100 mug), plasma LH was measured by radioimmunoassay. In the 3rd ventricle microinjection, PGE2 prodiced a significant rise in plasma LH. PGE1 and F2a did not significantly after plasma LH levels. In the median eminence, PGE2 and E1 produced a significant rise in plasma LH. PGF2a did not alter plasma LH levels. In the pituitary, PGE2 and E1 produced a significant rise in plasma LH. PGF2a did not alter plasma LH levels. These observations indicate that PGs act directly on the hypothalamic-pituitary axis, and that particular PG may be involved in the release of particular horomones from the hypothalamus and pituitary.", "contents": "Effects of microinjection of various prostaglandins into the 3rd ventricle, median eminence and pituitary on plasma LH in rats. The effects of microinjection of PG'S (PGE1, E2, F2a) into the 3rd ventricle, median eminence (ME) and anterior pituitary on plasma LH in rats were investigated. Blood samples were obtained by jugular puncture before, and 10 and 45 min after the injection of PGS (50 or 100 mug), plasma LH was measured by radioimmunoassay. In the 3rd ventricle microinjection, PGE2 prodiced a significant rise in plasma LH. PGE1 and F2a did not significantly after plasma LH levels. In the median eminence, PGE2 and E1 produced a significant rise in plasma LH. PGF2a did not alter plasma LH levels. In the pituitary, PGE2 and E1 produced a significant rise in plasma LH. PGF2a did not alter plasma LH levels. These observations indicate that PGs act directly on the hypothalamic-pituitary axis, and that particular PG may be involved in the release of particular horomones from the hypothalamus and pituitary."} {"id": "PMID:1278120", "title": "Origin of prolactin cells in the pituitary autografts in the renal capsule of young male and female rats.", "content": "Origin of the prolactin cells in the pituitary grafts autotransplanted into the renal capsule was electron microscopically investigated in young male and female rats. Prolactin cells may mainly originate from the completely degranulated acidophils after grafting in both sexes. The comprehensive degranulation of acidophils may be essential condition for the development of prolactin cells. Formation of initial prolactin granules is related to the Golgi apparatus in 3 and 6 days in the males. Even prolonged transplantation for the duration of 10 and 20 days failed to develop the typical prolactin cells storing large polymorphic granules in the grafts in the males. In the females, however, the population of prolactin cells became higher (20-30%) and their granulation was more rapidly advanced than in the male. Nine and 16 days after grafting quite numerous typical prolactin cells, characterized by the pronounced vesiculation of ER stored large polymorphic granules in the females. Progressive vesiculation of ER in degranulated acidophils may be the second necessary condition for establishing the prolactin cells. Thus, the entire course of cell conversion of acidophils into prolactin cells was observed in this study. All the graft cells including prolactin cells finally turned into the cells losing the respective individuality (10 days in the males; 32 days in the females). This fine structural similarity was striking in the males. We could not, however, deny the possibility of origination of prolactin cells from the follicular cells or their adjoining undifferentiated cells.", "contents": "Origin of prolactin cells in the pituitary autografts in the renal capsule of young male and female rats. Origin of the prolactin cells in the pituitary grafts autotransplanted into the renal capsule was electron microscopically investigated in young male and female rats. Prolactin cells may mainly originate from the completely degranulated acidophils after grafting in both sexes. The comprehensive degranulation of acidophils may be essential condition for the development of prolactin cells. Formation of initial prolactin granules is related to the Golgi apparatus in 3 and 6 days in the males. Even prolonged transplantation for the duration of 10 and 20 days failed to develop the typical prolactin cells storing large polymorphic granules in the grafts in the males. In the females, however, the population of prolactin cells became higher (20-30%) and their granulation was more rapidly advanced than in the male. Nine and 16 days after grafting quite numerous typical prolactin cells, characterized by the pronounced vesiculation of ER stored large polymorphic granules in the females. Progressive vesiculation of ER in degranulated acidophils may be the second necessary condition for establishing the prolactin cells. Thus, the entire course of cell conversion of acidophils into prolactin cells was observed in this study. All the graft cells including prolactin cells finally turned into the cells losing the respective individuality (10 days in the males; 32 days in the females). This fine structural similarity was striking in the males. We could not, however, deny the possibility of origination of prolactin cells from the follicular cells or their adjoining undifferentiated cells."} {"id": "PMID:1278121", "title": "Sterilization of female rats by neonatal placement of estradiol micropellets in anterior hypothalamus.", "content": "A pair of micropellets of a 1% or 10% estradiol (E2)-paraffin mixture (containing 0.2 or 2 mug E2, respectively) or paraffin alone were implanted subcutaneously or intracerebrally in 5-day-old female rats. Animals given 10% E2 pellets became sterilized regardless of loci of the pellets. Of those which had received 1% E2 pellets, only animals with micropellets in the anterior hypothalamus became sterilized. It is suggested that neuronal components which are affected irreversibly by neonatal estrogen treatment are localized in the anterior hypothalamus.", "contents": "Sterilization of female rats by neonatal placement of estradiol micropellets in anterior hypothalamus. A pair of micropellets of a 1% or 10% estradiol (E2)-paraffin mixture (containing 0.2 or 2 mug E2, respectively) or paraffin alone were implanted subcutaneously or intracerebrally in 5-day-old female rats. Animals given 10% E2 pellets became sterilized regardless of loci of the pellets. Of those which had received 1% E2 pellets, only animals with micropellets in the anterior hypothalamus became sterilized. It is suggested that neuronal components which are affected irreversibly by neonatal estrogen treatment are localized in the anterior hypothalamus."} {"id": "PMID:1278122", "title": "Alterations of insulin-secreting response to glucose in human infants during the early postnatal period.", "content": "Oral glucose tolerance tests were performed in healthy infants, aged one to 29 days. Capillary blood samples were obtained from heel stabs for estimation of glucose and insulin immediately before and 30, 60 and 120 minutes after the administration of glucose (2.0g per kg body weight). The younger infants tended to have delayed and diminished insulin responses to a glucose load than did older infants. The ratio of the increment of insulin concentration to the increment of glucose concentration at 30 minutes following a glucose load in younger infants, aged one to 20 days, was below 0.4. The ratio in infants older than 20 days was above 0.5. From these results it is evident that the pancreas of human infants begins to respond to the stimulation by glucose during the early postnatal period and this response becomes even obvious after 20 days of age.", "contents": "Alterations of insulin-secreting response to glucose in human infants during the early postnatal period. Oral glucose tolerance tests were performed in healthy infants, aged one to 29 days. Capillary blood samples were obtained from heel stabs for estimation of glucose and insulin immediately before and 30, 60 and 120 minutes after the administration of glucose (2.0g per kg body weight). The younger infants tended to have delayed and diminished insulin responses to a glucose load than did older infants. The ratio of the increment of insulin concentration to the increment of glucose concentration at 30 minutes following a glucose load in younger infants, aged one to 20 days, was below 0.4. The ratio in infants older than 20 days was above 0.5. From these results it is evident that the pancreas of human infants begins to respond to the stimulation by glucose during the early postnatal period and this response becomes even obvious after 20 days of age."} {"id": "PMID:1278123", "title": "In vitro biosynthesis of human chorionic follicle stimulating hormone.", "content": "In order to explore the possibility that human chorionic FSH (hCFSH) may be synthesized in vitro by the placenta and secreted into the culture media, chorionic tissue of the first trimester was cultivated in the radioactive medium prepared byadding 3H-proline and/or 14C-glutamic acid. Purification of biosynthesized hCFSH from the media was carried out by a combination of Sephadex G-100 gel filtration, DEAE-cellulose chromatography and polyacrylamide disc-gel electrophoresis...", "contents": "In vitro biosynthesis of human chorionic follicle stimulating hormone. In order to explore the possibility that human chorionic FSH (hCFSH) may be synthesized in vitro by the placenta and secreted into the culture media, chorionic tissue of the first trimester was cultivated in the radioactive medium prepared byadding 3H-proline and/or 14C-glutamic acid. Purification of biosynthesized hCFSH from the media was carried out by a combination of Sephadex G-100 gel filtration, DEAE-cellulose chromatography and polyacrylamide disc-gel electrophoresis..."} {"id": "PMID:1278124", "title": "Radioimmunoassay for secretin using Nalpha-tyrosylsecretin and [Tyr1]-secretin.", "content": "Sensitive radioimmunoassay for secretin was developed by using synthetic preparation of porcine secretin and its related analogs. The secretin-specific antisera with titers ranging 1: 20,000-1 : 150,000 were generated in rabbits against highly purified synthetic secretin. The labeled antigen was prepared by radioiodinating by the chloramine-T method synthetic secretin analog, Nalpha-tyrosylsecretin or [Tyr1]-secretin, both of which were proved to have almost identical immunoreactivities with that of secretin itself. The immunoassay was performed by the double-antibody method using synthetic secretin as standard. The lowest detectable amount of secretin in the present assays was 5-10pg/tube. Human duodenum extract with hot water contained secretin or secretin-like material that shows a parallel displacement curve to the standard in the immunoassay system used. Serum levels of secretin immunoreactivity in man rose up to 250 pg/ml by intraduodenal infusion of HCl and to 800-1,000 pg/ml by i.v. injection of 1 cu/kg of Boots natural secretin.", "contents": "Radioimmunoassay for secretin using Nalpha-tyrosylsecretin and [Tyr1]-secretin. Sensitive radioimmunoassay for secretin was developed by using synthetic preparation of porcine secretin and its related analogs. The secretin-specific antisera with titers ranging 1: 20,000-1 : 150,000 were generated in rabbits against highly purified synthetic secretin. The labeled antigen was prepared by radioiodinating by the chloramine-T method synthetic secretin analog, Nalpha-tyrosylsecretin or [Tyr1]-secretin, both of which were proved to have almost identical immunoreactivities with that of secretin itself. The immunoassay was performed by the double-antibody method using synthetic secretin as standard. The lowest detectable amount of secretin in the present assays was 5-10pg/tube. Human duodenum extract with hot water contained secretin or secretin-like material that shows a parallel displacement curve to the standard in the immunoassay system used. Serum levels of secretin immunoreactivity in man rose up to 250 pg/ml by intraduodenal infusion of HCl and to 800-1,000 pg/ml by i.v. injection of 1 cu/kg of Boots natural secretin."} {"id": "PMID:1278134", "title": "Differential effects of glucagon on induction of rat liver glucose-6-phosphate dehydrogenase by liver injury and dietary change.", "content": "Glucagon effectively prevented the increase in glucose-6-phosphate dehodrogenase activity of rat liver following the administration of a glucose-casein mixture without altering the amount of the diet consumed. However, the increase of the enzyme level in carbon tetrachloride-injured rat liver was virtually insensitive to glucagon. The results obtained gave further evidence for the difference between these two induction mechanisms of glucose-6-phosphate dehydrogenase.", "contents": "Differential effects of glucagon on induction of rat liver glucose-6-phosphate dehydrogenase by liver injury and dietary change. Glucagon effectively prevented the increase in glucose-6-phosphate dehodrogenase activity of rat liver following the administration of a glucose-casein mixture without altering the amount of the diet consumed. However, the increase of the enzyme level in carbon tetrachloride-injured rat liver was virtually insensitive to glucagon. The results obtained gave further evidence for the difference between these two induction mechanisms of glucose-6-phosphate dehydrogenase."} {"id": "PMID:1278135", "title": "Serum enolase and pyruvate kinase activities in the diagnosis of myocardial infarction.", "content": "Sequential determinations of serum enolase and pyruvate kinase (PK) activities were carried out in addition to routine enzyme assays on 191 patients admitted to a coronary care unit. The upper reference values established in 61 healthy laboratory staff members were 21 U/1 for enolase and 76 U/1 for PK. Of 99 patients with a confirmed diagnosis of myocardial infarction (MI), 97 manifested raised serum enolase during the period of observation; 85 of these patients had raised serum PK. The incidence of raised values for serum PK among patients considered not to have sustained infarction was similar to that shown by the routine enzymes, but serum enolase activity was much more frequently raised in these patients. The time-course of elevation of serum enolase and also that of PK are discussed in relation to the changes in other serum enzymes routinely measured for MI.", "contents": "Serum enolase and pyruvate kinase activities in the diagnosis of myocardial infarction. Sequential determinations of serum enolase and pyruvate kinase (PK) activities were carried out in addition to routine enzyme assays on 191 patients admitted to a coronary care unit. The upper reference values established in 61 healthy laboratory staff members were 21 U/1 for enolase and 76 U/1 for PK. Of 99 patients with a confirmed diagnosis of myocardial infarction (MI), 97 manifested raised serum enolase during the period of observation; 85 of these patients had raised serum PK. The incidence of raised values for serum PK among patients considered not to have sustained infarction was similar to that shown by the routine enzymes, but serum enolase activity was much more frequently raised in these patients. The time-course of elevation of serum enolase and also that of PK are discussed in relation to the changes in other serum enzymes routinely measured for MI."} {"id": "PMID:1278136", "title": "Red cell metabolism in high and low glutathione goats.", "content": "The following biochemical features were measured in the red blood cells of high and low glutathione goats: reduced glutathione (GSH) stability; GSH regeneration; glucose consumption; lactate production; levels of adenosine triphosphate and 2,3-diphosphoglycerate, and the activities of nine different enzymes of Embden-Meyerhof and pentose phosphate pathways of glucose metabolism. Apart from significant differences in the GSH stability the results of all the tests were found to be similar in the two groups.", "contents": "Red cell metabolism in high and low glutathione goats. The following biochemical features were measured in the red blood cells of high and low glutathione goats: reduced glutathione (GSH) stability; GSH regeneration; glucose consumption; lactate production; levels of adenosine triphosphate and 2,3-diphosphoglycerate, and the activities of nine different enzymes of Embden-Meyerhof and pentose phosphate pathways of glucose metabolism. Apart from significant differences in the GSH stability the results of all the tests were found to be similar in the two groups."} {"id": "PMID:1278137", "title": "Effect of ethanol and zinc on ALA-dehydratase activity in red blood cells.", "content": "Subcutaneous injection of zinc as sulphate to rats activates sigma-aminolaevulinic acid dehydratase (ALA-D) in red blood cells within few days of injection. This activation counteracts the inhibitory effect of orally administered ethanol.", "contents": "Effect of ethanol and zinc on ALA-dehydratase activity in red blood cells. Subcutaneous injection of zinc as sulphate to rats activates sigma-aminolaevulinic acid dehydratase (ALA-D) in red blood cells within few days of injection. This activation counteracts the inhibitory effect of orally administered ethanol."} {"id": "PMID:1278138", "title": "Phenacetin and the liver. The influence of phenacetin in acute and chronic doses on membrane-bound mitochondrial enzymes in the rat.", "content": "Following the administration of phenacetin in single and in multiple high doses, enzymes bound to the inner mitochondrial membrane of the liver were determined. Acute doses of phenacetin (75% of oral LD50) failed to produce any effect. The chronic administration of phenacetin provoked a small but statistically significant decrease in the TD-trnashydrogenase activity. This observation indicates that liver damage may occur in patients with phenacetin abuse.", "contents": "Phenacetin and the liver. The influence of phenacetin in acute and chronic doses on membrane-bound mitochondrial enzymes in the rat. Following the administration of phenacetin in single and in multiple high doses, enzymes bound to the inner mitochondrial membrane of the liver were determined. Acute doses of phenacetin (75% of oral LD50) failed to produce any effect. The chronic administration of phenacetin provoked a small but statistically significant decrease in the TD-trnashydrogenase activity. This observation indicates that liver damage may occur in patients with phenacetin abuse."} {"id": "PMID:1278149", "title": "The structure of kinetoplast DNA. 1. The mini-circles of Crithidia lucilae are heterogeneous in base sequence.", "content": "We have analysed limit digests of mini-circles from kinetoplast DNA of Crithidia luciliae by gel electrophoresis. Endonucleases HapII and AluI cut the circles into at least 37 and 21 fragments, respectively, and leave no circles intact. In both cases the added molecular weights of the fragments, estimated from mobility in gels, exceeds 18 X 10(6), i.e. more than 12 times the molecular weight of the mini-circle DNA. Endonucleases HindII + III, EcoRI and HpaI cut only part of the circles. These results show that the mini-circles are heterogeneous in base sequence. Different sequence classes are present in different amounts. DNA-DNA renaturation analysis of mini-circle DNA yields a complexity of about 3 X 10(6), i.e. twice the molecular weight on one mini-circle. The delta tm of native and renatured duplexes is about 1 degree C, showing that the sequence heterogeneity is a micro-heterogeneity. Electron microscopy, gel electrophoresis and sedimentation analysis show that the circles that are not cut by endonucleases HindII + III remain catenated in very large associations. These associations lack the 'rosette' structures and the long edge loops characteristic of intact kinetoplast DNA. This suggests that the mini-circle classes cut by endonucleases HindII + III are present throughout the network and that the maxi-circle component of the network (see accompanying paper) is not essential to hold the network together. Prolonged electrophoresis on 1.5% or 2% agarose gels resolves the open mini-circles into three and linearized mini-circles into four bands, present in different amounts. We conclude that the mini-circles are also heterogeneous in size, the difference in size between the two extreme size classes being 4% of the contour length. Digestion with endonuclease HapII shows that at least three out of these four bands differ in sequence. Possible mechanisms that could account for the micro-heterogeneity in sequence of mini-circles are discussed.", "contents": "The structure of kinetoplast DNA. 1. The mini-circles of Crithidia lucilae are heterogeneous in base sequence. We have analysed limit digests of mini-circles from kinetoplast DNA of Crithidia luciliae by gel electrophoresis. Endonucleases HapII and AluI cut the circles into at least 37 and 21 fragments, respectively, and leave no circles intact. In both cases the added molecular weights of the fragments, estimated from mobility in gels, exceeds 18 X 10(6), i.e. more than 12 times the molecular weight of the mini-circle DNA. Endonucleases HindII + III, EcoRI and HpaI cut only part of the circles. These results show that the mini-circles are heterogeneous in base sequence. Different sequence classes are present in different amounts. DNA-DNA renaturation analysis of mini-circle DNA yields a complexity of about 3 X 10(6), i.e. twice the molecular weight on one mini-circle. The delta tm of native and renatured duplexes is about 1 degree C, showing that the sequence heterogeneity is a micro-heterogeneity. Electron microscopy, gel electrophoresis and sedimentation analysis show that the circles that are not cut by endonucleases HindII + III remain catenated in very large associations. These associations lack the 'rosette' structures and the long edge loops characteristic of intact kinetoplast DNA. This suggests that the mini-circle classes cut by endonucleases HindII + III are present throughout the network and that the maxi-circle component of the network (see accompanying paper) is not essential to hold the network together. Prolonged electrophoresis on 1.5% or 2% agarose gels resolves the open mini-circles into three and linearized mini-circles into four bands, present in different amounts. We conclude that the mini-circles are also heterogeneous in size, the difference in size between the two extreme size classes being 4% of the contour length. Digestion with endonuclease HapII shows that at least three out of these four bands differ in sequence. Possible mechanisms that could account for the micro-heterogeneity in sequence of mini-circles are discussed."} {"id": "PMID:1278150", "title": "Translation of the mRNA for rabbit uteroglobin in cell-free systems. Evidence for a precursor protein.", "content": "Uteroglobin, an hormonally induced protein composed of two similar subunits, represents around 50% of the proteins synthesized and secreted into the uterine lumen of rabbits treated sequentially with estradiol and progesterone. The endometrium of these animals was used as a source for the isolation of the mRNA for uteroglobin. Poly(A)-rich RNA, extracted from purified polysomes with phenol chloroform and isolated on oligo(dT)-cellulose columns, contains one fourth of the total protein coding activity of the endometrium. Between 20--25% of the polypeptides synthesized by this RNA in cell-free systems derived from Krebs II ascites cells or wheat germs react with a monospecific antiserum prepared in guinea pigs against uteroglobin. The material bound to the antibody was identified as a precursor of uteroglobin according to the following criteria. 1. The product synthesized in vitro can be displaced from the complex with the specific immunoglobulin by purified uteroglobin. 2. Analysis of the immunoprecipitate on polyacrylamide gels containing urea and dodecylsulfate demonstrate the existence of a single labelled polypeptide with an apparent molecular weight larger than the uteroglobin subunits. 3. The tryptic digest of this polypeptide, labelled in vitro with [3H]lysine, shares seven peptides with mature uteroglobin labelled with the same amino acid in perfused uteri, and exhibits and additional peptide not present in uteroglobin. 4. Injection of the same mRNA preparation into Xenopus oocytes results in the production of uteroglobin. The endometrium of intact animals treated with estradiol alone also contains the same mRNA bound to polysomes but in a smaller proportion, indicating that the progesterone-induced synthesis of uteroglobin is accompanied by an accumulation of the specific mRNA in the polysomes.", "contents": "Translation of the mRNA for rabbit uteroglobin in cell-free systems. Evidence for a precursor protein. Uteroglobin, an hormonally induced protein composed of two similar subunits, represents around 50% of the proteins synthesized and secreted into the uterine lumen of rabbits treated sequentially with estradiol and progesterone. The endometrium of these animals was used as a source for the isolation of the mRNA for uteroglobin. Poly(A)-rich RNA, extracted from purified polysomes with phenol chloroform and isolated on oligo(dT)-cellulose columns, contains one fourth of the total protein coding activity of the endometrium. Between 20--25% of the polypeptides synthesized by this RNA in cell-free systems derived from Krebs II ascites cells or wheat germs react with a monospecific antiserum prepared in guinea pigs against uteroglobin. The material bound to the antibody was identified as a precursor of uteroglobin according to the following criteria. 1. The product synthesized in vitro can be displaced from the complex with the specific immunoglobulin by purified uteroglobin. 2. Analysis of the immunoprecipitate on polyacrylamide gels containing urea and dodecylsulfate demonstrate the existence of a single labelled polypeptide with an apparent molecular weight larger than the uteroglobin subunits. 3. The tryptic digest of this polypeptide, labelled in vitro with [3H]lysine, shares seven peptides with mature uteroglobin labelled with the same amino acid in perfused uteri, and exhibits and additional peptide not present in uteroglobin. 4. Injection of the same mRNA preparation into Xenopus oocytes results in the production of uteroglobin. The endometrium of intact animals treated with estradiol alone also contains the same mRNA bound to polysomes but in a smaller proportion, indicating that the progesterone-induced synthesis of uteroglobin is accompanied by an accumulation of the specific mRNA in the polysomes."} {"id": "PMID:1278151", "title": "The structure of kinetoplast DNA. 2. Characterization of a novel component of high complexity present in the kinetoplast DNA network of Crithidia luciliae.", "content": "1. Degradation of highly purified kinetoplast DNA (kDNA) networks with restriction endonucleases yields \"extra\" bands in agarose gels that are absent from digests of mini-circles. Each of the five endonucleases tested, i.e. AluI, HapII, EcoRI, Hsu and HindII + III, yields a unique set of \"extra\" bands. The \"extra\" bands consist of linear DNA; they are not mini-circle oligomers and their added molecular weight, calculated from mobility in gels, are around 2 X 10(7). Double digests with two restriction endonucleases yield a new set of \"extra\" bands, showing that the \"extra\" bands obtained with different enzymes are all derived from the same complex component of kDNA. In digests of 32P-labelled kDNA an average of 2.3% of the radioactivity is recovered in the \"extra\" bands. 2. Treatment of kDNA networks with the single-strand-specific S1 nuclease of Aspergillus oryzae preferentially releases a linear DNA with a molecular weight of 26 X 10(6), calculated from mobility in gels. We present evidence that the 'extra' bands obtained with restriction endonucleases are derived from this component. 3. DNA-DNA renaturation analysis of fragmented kDNA shows the presence of a minor complex component with a complexity of about 3 X 10(7), making up less than 10% of the total kDNA. 4. From these results we conclude that 3--5% of the kDNA consists of a homogeneous class of maxi-circles catenated in the mini-circle network. The molecular weight of these maxi-circles is about 26 X 10(6) and they contain a unique, non-repetitive, non-mini-circle nucleotide sequence. This component is a prime candidate for the true mitochondrial DNA of trypanosomes.", "contents": "The structure of kinetoplast DNA. 2. Characterization of a novel component of high complexity present in the kinetoplast DNA network of Crithidia luciliae. 1. Degradation of highly purified kinetoplast DNA (kDNA) networks with restriction endonucleases yields \"extra\" bands in agarose gels that are absent from digests of mini-circles. Each of the five endonucleases tested, i.e. AluI, HapII, EcoRI, Hsu and HindII + III, yields a unique set of \"extra\" bands. The \"extra\" bands consist of linear DNA; they are not mini-circle oligomers and their added molecular weight, calculated from mobility in gels, are around 2 X 10(7). Double digests with two restriction endonucleases yield a new set of \"extra\" bands, showing that the \"extra\" bands obtained with different enzymes are all derived from the same complex component of kDNA. In digests of 32P-labelled kDNA an average of 2.3% of the radioactivity is recovered in the \"extra\" bands. 2. Treatment of kDNA networks with the single-strand-specific S1 nuclease of Aspergillus oryzae preferentially releases a linear DNA with a molecular weight of 26 X 10(6), calculated from mobility in gels. We present evidence that the 'extra' bands obtained with restriction endonucleases are derived from this component. 3. DNA-DNA renaturation analysis of fragmented kDNA shows the presence of a minor complex component with a complexity of about 3 X 10(7), making up less than 10% of the total kDNA. 4. From these results we conclude that 3--5% of the kDNA consists of a homogeneous class of maxi-circles catenated in the mini-circle network. The molecular weight of these maxi-circles is about 26 X 10(6) and they contain a unique, non-repetitive, non-mini-circle nucleotide sequence. This component is a prime candidate for the true mitochondrial DNA of trypanosomes."} {"id": "PMID:1278152", "title": "The incorporation of newly synthesized RNA into nuclear ribonucleoprotein particles after oestrogen administration to immature rats.", "content": "Ribonucleoprotein particles, known as informofers or heterogeneous nuclear ribonucleoprotein particles (hnRNA - protein), have been extracted from rat uterine nuclei and found to have properties similar to those characterized from other tissues. Incorporation of RNA precursors into the RNA of these particles is stimulated up to 8-fold by oestrogen administration to rats. When uteri are dissected from oestrogen-treated rats and incubated in vitro with radioactive RNA precursor, only the RNA in the ribonucleoprotein particles is synthesized at a rate faster than can be accounted for by increase in the uptake of precursor. This contrasts with previous studies where both hormone treatment an incorporation of radioactive precursor were performed in vivo and the synthesis of all RNA species was stimulated [Knowler, J.T. and Smellie, R.M.S. (1971) Biochem. J. 125, 605--614; Knowler, J.T. and Smellie, R.M.S. (1973) Biochem. J. 131, 689--697].", "contents": "The incorporation of newly synthesized RNA into nuclear ribonucleoprotein particles after oestrogen administration to immature rats. Ribonucleoprotein particles, known as informofers or heterogeneous nuclear ribonucleoprotein particles (hnRNA - protein), have been extracted from rat uterine nuclei and found to have properties similar to those characterized from other tissues. Incorporation of RNA precursors into the RNA of these particles is stimulated up to 8-fold by oestrogen administration to rats. When uteri are dissected from oestrogen-treated rats and incubated in vitro with radioactive RNA precursor, only the RNA in the ribonucleoprotein particles is synthesized at a rate faster than can be accounted for by increase in the uptake of precursor. This contrasts with previous studies where both hormone treatment an incorporation of radioactive precursor were performed in vivo and the synthesis of all RNA species was stimulated [Knowler, J.T. and Smellie, R.M.S. (1971) Biochem. J. 125, 605--614; Knowler, J.T. and Smellie, R.M.S. (1973) Biochem. J. 131, 689--697]."} {"id": "PMID:1278153", "title": "Simultaneous translation of structural and nonstructural proteins from Semliki-forest-virus RNA in two eukaryotic systems in vitro.", "content": "The Semliki Forest virus genome, 42-S RNA, and the virus-specific intracellular 26-S RNA were translated in two cell-free protein-synthesising systems, the wheat germ extract, and a partially purified system from mammalian tissues. The 26-S RNA directed the synthesis of structual proteins only, as revealed by tryptic peptide mapping. About 75--80% of the radioactivity in the products comigrated with capsid and about 4--8% with envelope protein peptides. All the capsid peptides and the full-sized capsid protein were found in the products in vitro, no complete envelope protein was formed and fewer than half of the envelope peptides were detected. This result is consistent with reports that there is only one initiation site for the translation of virus structural proteins, and that the capsid protein is N-terminal in the polyprotein followed by envelope proteins. The systems programmed with 42-S RNA yielded virtually the same structural peptides. However, the bulk of the radioactivity was in peptides which did not comigrate with the structural ones. These peptides were mostly associated with relatively small-sized products. This shows that Semliki Forest virus 42-S RNA has at least two initiation sites, one for the structural proteins and the other(s) for the nonstructural proteins.", "contents": "Simultaneous translation of structural and nonstructural proteins from Semliki-forest-virus RNA in two eukaryotic systems in vitro. The Semliki Forest virus genome, 42-S RNA, and the virus-specific intracellular 26-S RNA were translated in two cell-free protein-synthesising systems, the wheat germ extract, and a partially purified system from mammalian tissues. The 26-S RNA directed the synthesis of structual proteins only, as revealed by tryptic peptide mapping. About 75--80% of the radioactivity in the products comigrated with capsid and about 4--8% with envelope protein peptides. All the capsid peptides and the full-sized capsid protein were found in the products in vitro, no complete envelope protein was formed and fewer than half of the envelope peptides were detected. This result is consistent with reports that there is only one initiation site for the translation of virus structural proteins, and that the capsid protein is N-terminal in the polyprotein followed by envelope proteins. The systems programmed with 42-S RNA yielded virtually the same structural peptides. However, the bulk of the radioactivity was in peptides which did not comigrate with the structural ones. These peptides were mostly associated with relatively small-sized products. This shows that Semliki Forest virus 42-S RNA has at least two initiation sites, one for the structural proteins and the other(s) for the nonstructural proteins."} {"id": "PMID:1278154", "title": "The selective blocking of the polymerization reaction of striated muscle actin leading to a derivative suitable for crystallization. Modification of Tyr-53 by 5-diazonium-(1H)tetrazole.", "content": "The polymerization reaction of rabbit muscle actin was completely inhibited by reaction of one amino acid side chain per protein monomer with 5-diazonium-(1H)[14C]tetrazole. A tryptic peptide fingerprint showed a single peptide labeled by the reagent. The peptide was isolated and the labeled amino acid identified by amino acid analysis as Tyr-53. This side chain is not accessible to the reagent in F-actin. The modification is compared to similar inhibitions by other reagents.", "contents": "The selective blocking of the polymerization reaction of striated muscle actin leading to a derivative suitable for crystallization. Modification of Tyr-53 by 5-diazonium-(1H)tetrazole. The polymerization reaction of rabbit muscle actin was completely inhibited by reaction of one amino acid side chain per protein monomer with 5-diazonium-(1H)[14C]tetrazole. A tryptic peptide fingerprint showed a single peptide labeled by the reagent. The peptide was isolated and the labeled amino acid identified by amino acid analysis as Tyr-53. This side chain is not accessible to the reagent in F-actin. The modification is compared to similar inhibitions by other reagents."} {"id": "PMID:1278155", "title": "Snake venom toxins. The amino-acid sequences of three toxins (CM-8, CM-11 and CM-13a) from Naja haje annulifera (Egyptian cobra) venom.", "content": "Three toxins (CM-8, CM-11, and CM-13a) were purified from the venom of Naja haje annulifera by gel filtration on Sephadex G-50 and by ion-exchange chromatography on CM-cellulose. Whereas toxin CM-8 and CM-11 comprise 60 amino acid residues, toxin CM-13a contains 61 residues. All three toxins are cross-linked by four intrachain disulphide bridges. The complete amino acid sequences of these toxins have been elucidated. The reduced and S-carboxymethylated toxins were digested with trypsin and chymotrypsin and the peptides purified by ion-exchange chromatography, gel filtration and chromatography or electrophoresis on paper. The Edman procedure, either through the use of the automatic sequencer or by manual manipulation, was employed to obtain the sequence of the intact toxins and the pure peptides. The chymotryptic digests provided the necessary overlapping peptides which allowed the alignment of the tryptic peptides. The properties of the three toxins were compared with those of the cytotoxin group. The toxicities the serological properties, the sequences and the invariant amino acid residues of toxin CM-8 and CM-11 resemble the corresponding properties of the cytotoxin group. The sequence and serological properties of toxin CM-13a show that it is related to the cytotoxin group, but its toxicity is much lower than those encountered in the cytotoxin group.", "contents": "Snake venom toxins. The amino-acid sequences of three toxins (CM-8, CM-11 and CM-13a) from Naja haje annulifera (Egyptian cobra) venom. Three toxins (CM-8, CM-11, and CM-13a) were purified from the venom of Naja haje annulifera by gel filtration on Sephadex G-50 and by ion-exchange chromatography on CM-cellulose. Whereas toxin CM-8 and CM-11 comprise 60 amino acid residues, toxin CM-13a contains 61 residues. All three toxins are cross-linked by four intrachain disulphide bridges. The complete amino acid sequences of these toxins have been elucidated. The reduced and S-carboxymethylated toxins were digested with trypsin and chymotrypsin and the peptides purified by ion-exchange chromatography, gel filtration and chromatography or electrophoresis on paper. The Edman procedure, either through the use of the automatic sequencer or by manual manipulation, was employed to obtain the sequence of the intact toxins and the pure peptides. The chymotryptic digests provided the necessary overlapping peptides which allowed the alignment of the tryptic peptides. The properties of the three toxins were compared with those of the cytotoxin group. The toxicities the serological properties, the sequences and the invariant amino acid residues of toxin CM-8 and CM-11 resemble the corresponding properties of the cytotoxin group. The sequence and serological properties of toxin CM-13a show that it is related to the cytotoxin group, but its toxicity is much lower than those encountered in the cytotoxin group."} {"id": "PMID:1278156", "title": "The enzyme complex citramalate lyase from Clostridium tetanomorphum.", "content": "1. The enzyme citramalate from Clostridium tetanomorphum is not stable in crude extracts. However, the inactive enzyme can be reactivated by incubation with dithioerythritol followed by acetylation with acetic anhydride. Reactivation was also obtained with acetate, ATP, MgCl2 and acetate : SH-enzyme ligases (AMP) from C. tetanomorphum or Klebsiella aerogenes. 2. Incubation of the inactive enzyme with iodoacetate resulted in rapid loss of enzymic activity as determined by reactivation with acetic anhydride whereas the active enzyme was stable in the presence of iodoacetate. Using ido[2-(14)C]acetate the sites of carboxymethylation and acetylation where identified as cysteamine residues of the enzyme. The results demonstrate that the active enzyme contains acetyl thiolester residues which play the central role in the catalytic mechanism. 3. Citramalate lyase was purified by a procedure almost identical to that already described for citrate lyase from K. aerogenes. The molecular weight of citramalate lyase is equal to that of citrate lyase (Mr = 5.2--5.8 X 10(5)) as estimated by gel chromatography and sucrose gradient centrifugation. Polyacrylamide gel elctrophoresis of citramalate lyase in sodium dodecylsulfate yielded three polypeptide chains (Mr: alpha 5.3--5.6 X 10(4); beta 3.3--3.6 X 10(4); gamma 1.0--1.2 X 10(4)) in probably equal molar amounts. These data lead to a hexameric structure (alpha,beta,gamma)6 of the complete enzyme. 4. Pantothenate (5 mol/mol of enzyme) and the essential cysteamine residues were exclusively present in the gamma-chain, the acyl carrier protein of citramalate lyase. The acyl exchange and cleavage functions, probably catalysed by the alpha and beta-subunits, were measured with acyl-CoA derivatives which were able to substitute for the natural acyl carrier. 5. The results demonstrate that citramalate lyase is an enzyme complex with structure and functions closely resembling those of citrate lyase. Although the similarity between citramalate lyase and citrate lyases from various organisms suggests a close evolutionary relationship, these occur in very different, unrelated bacteria. A parallel situation found in the distribution of the nitrogenase system among procaryotes is discussed.", "contents": "The enzyme complex citramalate lyase from Clostridium tetanomorphum. 1. The enzyme citramalate from Clostridium tetanomorphum is not stable in crude extracts. However, the inactive enzyme can be reactivated by incubation with dithioerythritol followed by acetylation with acetic anhydride. Reactivation was also obtained with acetate, ATP, MgCl2 and acetate : SH-enzyme ligases (AMP) from C. tetanomorphum or Klebsiella aerogenes. 2. Incubation of the inactive enzyme with iodoacetate resulted in rapid loss of enzymic activity as determined by reactivation with acetic anhydride whereas the active enzyme was stable in the presence of iodoacetate. Using ido[2-(14)C]acetate the sites of carboxymethylation and acetylation where identified as cysteamine residues of the enzyme. The results demonstrate that the active enzyme contains acetyl thiolester residues which play the central role in the catalytic mechanism. 3. Citramalate lyase was purified by a procedure almost identical to that already described for citrate lyase from K. aerogenes. The molecular weight of citramalate lyase is equal to that of citrate lyase (Mr = 5.2--5.8 X 10(5)) as estimated by gel chromatography and sucrose gradient centrifugation. Polyacrylamide gel elctrophoresis of citramalate lyase in sodium dodecylsulfate yielded three polypeptide chains (Mr: alpha 5.3--5.6 X 10(4); beta 3.3--3.6 X 10(4); gamma 1.0--1.2 X 10(4)) in probably equal molar amounts. These data lead to a hexameric structure (alpha,beta,gamma)6 of the complete enzyme. 4. Pantothenate (5 mol/mol of enzyme) and the essential cysteamine residues were exclusively present in the gamma-chain, the acyl carrier protein of citramalate lyase. The acyl exchange and cleavage functions, probably catalysed by the alpha and beta-subunits, were measured with acyl-CoA derivatives which were able to substitute for the natural acyl carrier. 5. The results demonstrate that citramalate lyase is an enzyme complex with structure and functions closely resembling those of citrate lyase. Although the similarity between citramalate lyase and citrate lyases from various organisms suggests a close evolutionary relationship, these occur in very different, unrelated bacteria. A parallel situation found in the distribution of the nitrogenase system among procaryotes is discussed."} {"id": "PMID:1278157", "title": "Acetic anhydride: an intermediate analogue in the acyl-exchange reaction of citramalate lyase.", "content": "1. Reactivation of deacetyl citramalate lyase by acetic anhydride proceeds through an enzyme-anhydride complex prior to actual acetylation. The reaction is inhibited by citramalate which is competitive with acetic anhydride. 2. A corresponding complex is an intermediate in the carboxymethylation of deacetyl enzyme by iodoacetate. However, the inhibition of this reaction by S-citramalate appears to be non-competitive with iodoacetate. 3. The results lead to the conclusion that acetic anhydride can be regarded as a structural analogue of citramalic acetic anhydride, the proposed intermediate in the acyl exchange reaction on citramalate lyase. 4. The formation of 6-citryl thiolester from the 1-thiolester via the cyclic citric anhydride provides a chemicla model for enzymic acyl exchange. 5. The data suggest that anhydrides are of general importance in acyl exchange reactions of thiolesters.", "contents": "Acetic anhydride: an intermediate analogue in the acyl-exchange reaction of citramalate lyase. 1. Reactivation of deacetyl citramalate lyase by acetic anhydride proceeds through an enzyme-anhydride complex prior to actual acetylation. The reaction is inhibited by citramalate which is competitive with acetic anhydride. 2. A corresponding complex is an intermediate in the carboxymethylation of deacetyl enzyme by iodoacetate. However, the inhibition of this reaction by S-citramalate appears to be non-competitive with iodoacetate. 3. The results lead to the conclusion that acetic anhydride can be regarded as a structural analogue of citramalic acetic anhydride, the proposed intermediate in the acyl exchange reaction on citramalate lyase. 4. The formation of 6-citryl thiolester from the 1-thiolester via the cyclic citric anhydride provides a chemicla model for enzymic acyl exchange. 5. The data suggest that anhydrides are of general importance in acyl exchange reactions of thiolesters."} {"id": "PMID:1278158", "title": "Studies on the role of uncharged tRNA in pleiotypic response of animal cells.", "content": "Experiments were carried out to assess the physiological significance of the charging level of tRNA. Histidinol, a competitve inhibitor of charging of tRNAHis, was used to induce uncharged tRNA in mammalian cells. It is demonstrated that both in the presence of histidinol and under histidine depletion about 40% of the tRNAHis is uncharged. Concomitant with this appearance of uncharged tRNA(a) the pools of GTP and ATP are decreased rapidly by 25--30%; (b) the synthesis of both protein and ribosomal RNA is inhibited, whereas that of nucleoplasmic RNA is not affected; (c) the uptake of 2-deoxyglucose, phosphate, Ca2+; uridine and adenosine is inhibited; and (d) the growth of 3T6 fibroblasts is arrested. It is suggested that the appearence of uncharged tRNA is one of the earliest events occurring under conditions of amino acid starvation, which in turn causes the various metabolic changes observed.", "contents": "Studies on the role of uncharged tRNA in pleiotypic response of animal cells. Experiments were carried out to assess the physiological significance of the charging level of tRNA. Histidinol, a competitve inhibitor of charging of tRNAHis, was used to induce uncharged tRNA in mammalian cells. It is demonstrated that both in the presence of histidinol and under histidine depletion about 40% of the tRNAHis is uncharged. Concomitant with this appearance of uncharged tRNA(a) the pools of GTP and ATP are decreased rapidly by 25--30%; (b) the synthesis of both protein and ribosomal RNA is inhibited, whereas that of nucleoplasmic RNA is not affected; (c) the uptake of 2-deoxyglucose, phosphate, Ca2+; uridine and adenosine is inhibited; and (d) the growth of 3T6 fibroblasts is arrested. It is suggested that the appearence of uncharged tRNA is one of the earliest events occurring under conditions of amino acid starvation, which in turn causes the various metabolic changes observed."} {"id": "PMID:1278159", "title": "On the mechanism of malonyl-CoA-independent fatty-acid synthesis. Different properties of the mitochondrial chain elongation and enoylCoA reductase in various tissues.", "content": "1. NADPH-specific mitochondrial enoyl-CoA reductase can be assayed by a sensitive radioactive test, employing tritium-labelled NADPH, synthesized in a prefixed reaction from D-[1-3H]-glucose via the hexokinase and glucose-6-phosphate dehydrogenase reactions. 2. Liver, kidney cortex, heart muscle, skeletal muscle, brown adipose tissue, brain cortex, and aortic intimal tissue are investigated concerning chain lengths specificity of the chain elongation and the enoyl-CoA reductase. Medium-chain acyl-CoA compounds prove to be the best primers for the chain elongation. Enoyl-CoA reductases still show large incorporation rates with hexadecenoyl-CoA. 3. The differences in the chain lengths specificity of the chain elongation and enoyl-CoA reductase can be explained by the inhibitory effect of long-chain acyl-CoA derivatives on the 3-hydroxyacyl-CoA dehydrogenase. 4. The nucleotide specificity in the different tissues reveals two types of chain elongation: In addition to liver and kidney cortex, mitochondria of brown adipose tissue need NADH + NADPH for optimal chain elongation, whereas heart muscle, skeletal muscle and aortic intimal mitochondria only need NADH. 5. Different physiological roles are proposed for the two types. The \"heart type\" may be of importance in the conservation of reducing equivalents or acetate units in the anaerobic state, the \"liver type\" may play a role in the transfer of hydrogen from NADPH to the respiratory chain. In addition, the mitochondrial chain elongation may serve as bypass of the first part of the respiratory chain.", "contents": "On the mechanism of malonyl-CoA-independent fatty-acid synthesis. Different properties of the mitochondrial chain elongation and enoylCoA reductase in various tissues. 1. NADPH-specific mitochondrial enoyl-CoA reductase can be assayed by a sensitive radioactive test, employing tritium-labelled NADPH, synthesized in a prefixed reaction from D-[1-3H]-glucose via the hexokinase and glucose-6-phosphate dehydrogenase reactions. 2. Liver, kidney cortex, heart muscle, skeletal muscle, brown adipose tissue, brain cortex, and aortic intimal tissue are investigated concerning chain lengths specificity of the chain elongation and the enoyl-CoA reductase. Medium-chain acyl-CoA compounds prove to be the best primers for the chain elongation. Enoyl-CoA reductases still show large incorporation rates with hexadecenoyl-CoA. 3. The differences in the chain lengths specificity of the chain elongation and enoyl-CoA reductase can be explained by the inhibitory effect of long-chain acyl-CoA derivatives on the 3-hydroxyacyl-CoA dehydrogenase. 4. The nucleotide specificity in the different tissues reveals two types of chain elongation: In addition to liver and kidney cortex, mitochondria of brown adipose tissue need NADH + NADPH for optimal chain elongation, whereas heart muscle, skeletal muscle and aortic intimal mitochondria only need NADH. 5. Different physiological roles are proposed for the two types. The \"heart type\" may be of importance in the conservation of reducing equivalents or acetate units in the anaerobic state, the \"liver type\" may play a role in the transfer of hydrogen from NADPH to the respiratory chain. In addition, the mitochondrial chain elongation may serve as bypass of the first part of the respiratory chain."} {"id": "PMID:1278160", "title": "The binding of tritiated elongation-factors 1 and 2 to ribosomes from Krebs II mouse ascites-tumore cells. The influence of various antibiotics and toxins.", "content": "The effect of a number of different antibiotics and toxins on the capacity of Krebs II mouse ascites ribosomes to bind 3H-labelled elongation factors (EF-1 and EF-2) has been examined. It was found that abrin and ricin inhibit the binding of EF-2, while diphtheria toxin, sparsomycin, streptovitacin A, and cycloheximide had essentially no effect on its binding. Of the other compounds examined, sparsomycin was unique in its capacity, under some circumstances, to significantly affect the binding of aminoacyl-tRNA and EF-1 to ribosomes. Fusidic acid appears to nonspecifically enhance the binding of both EF-1 and EF-2.", "contents": "The binding of tritiated elongation-factors 1 and 2 to ribosomes from Krebs II mouse ascites-tumore cells. The influence of various antibiotics and toxins. The effect of a number of different antibiotics and toxins on the capacity of Krebs II mouse ascites ribosomes to bind 3H-labelled elongation factors (EF-1 and EF-2) has been examined. It was found that abrin and ricin inhibit the binding of EF-2, while diphtheria toxin, sparsomycin, streptovitacin A, and cycloheximide had essentially no effect on its binding. Of the other compounds examined, sparsomycin was unique in its capacity, under some circumstances, to significantly affect the binding of aminoacyl-tRNA and EF-1 to ribosomes. Fusidic acid appears to nonspecifically enhance the binding of both EF-1 and EF-2."} {"id": "PMID:1278161", "title": "Kinetic isotope effects on the catalytic activity of pig-plasma benzylamine oxidase.", "content": "1. Isotope effects on the catalytic activity of benzylamine oxidase at pH 7 and 9 have been studied by steady-state and transient-state kinetics methods, using [alpha,alpha-2H]benzylamine as the substrate. 2. Replacement of the alpha-hydrogen atoms in benzylamine by deuterium has no significant effect on substrate-binding to benzylamine oxidase, neither does it affect the rate of reoxidation of the reduced form of the enzyme. Conversion of the primarily formed enzyme-substrate complex into the reduced enzyme species, however, exhibits an isotope effect of about 3. 3. The data obtained are consistent with a mechanism in which reduction of benzylamine oxidase takes place by a rapid pre-equilibration between enzyme and substrate to form an amine-pyridoxal Schiff-base, which is then tautomerized by a comparatively slow prototropic shift to an amino aldehyde-pyridoxamine Schiff-base from which there is a rapid hydrolytic release of the aldehyde product corresponding to the amine substrate. Proton abstraction from the alpha-carbon of the amine moiety in the primary Schiff-base appears to be at least partially rate-limiting for the tautomerization step, and hence for the entire process of enzyme reduction.", "contents": "Kinetic isotope effects on the catalytic activity of pig-plasma benzylamine oxidase. 1. Isotope effects on the catalytic activity of benzylamine oxidase at pH 7 and 9 have been studied by steady-state and transient-state kinetics methods, using [alpha,alpha-2H]benzylamine as the substrate. 2. Replacement of the alpha-hydrogen atoms in benzylamine by deuterium has no significant effect on substrate-binding to benzylamine oxidase, neither does it affect the rate of reoxidation of the reduced form of the enzyme. Conversion of the primarily formed enzyme-substrate complex into the reduced enzyme species, however, exhibits an isotope effect of about 3. 3. The data obtained are consistent with a mechanism in which reduction of benzylamine oxidase takes place by a rapid pre-equilibration between enzyme and substrate to form an amine-pyridoxal Schiff-base, which is then tautomerized by a comparatively slow prototropic shift to an amino aldehyde-pyridoxamine Schiff-base from which there is a rapid hydrolytic release of the aldehyde product corresponding to the amine substrate. Proton abstraction from the alpha-carbon of the amine moiety in the primary Schiff-base appears to be at least partially rate-limiting for the tautomerization step, and hence for the entire process of enzyme reduction."} {"id": "PMID:1278162", "title": "Action of thrombin on ovine, bovine and human pituitary growth hormones.", "content": "1. This communication reports the action of bovine thrombin on ovine, bovine and human growth hormones. Thrombin cleavage was shown to be restricted to a single homologous peptide bond in all three growth hormones (at sequence positions 133--134 of the ovine and bovine hormones). 2. Ovine growth hormone was the most sensitive to the action of thrombin, bovine growth hormone was attacked to a relatively less extent, and human growth hormone was the most resistant to the enzyme. 3. After reduction and carbamidomethylation of the disulfide bonds in thrombin modified ovine growth hormone, the two fragments (residues 1--133 and 134--191) were isolated. The large NH2-terminal thrombin fragment of the hormone (residues 1--133) was found to be inactive in the rat tibia test, whereas a tryptic fragment (residues 96--133) isolated in an independent way gave measurable responses.", "contents": "Action of thrombin on ovine, bovine and human pituitary growth hormones. 1. This communication reports the action of bovine thrombin on ovine, bovine and human growth hormones. Thrombin cleavage was shown to be restricted to a single homologous peptide bond in all three growth hormones (at sequence positions 133--134 of the ovine and bovine hormones). 2. Ovine growth hormone was the most sensitive to the action of thrombin, bovine growth hormone was attacked to a relatively less extent, and human growth hormone was the most resistant to the enzyme. 3. After reduction and carbamidomethylation of the disulfide bonds in thrombin modified ovine growth hormone, the two fragments (residues 1--133 and 134--191) were isolated. The large NH2-terminal thrombin fragment of the hormone (residues 1--133) was found to be inactive in the rat tibia test, whereas a tryptic fragment (residues 96--133) isolated in an independent way gave measurable responses."} {"id": "PMID:1278163", "title": "The use of metrizamide as a density-gradient medium in studies of rat-liver polysomes.", "content": "The behaviour of rat liver cytoplasmic ribonucleoproteins in metrizamide has been studied to determine whether the iodinated compound would offer any advantage over other centrifugation media for studies of polysome structure and function. 1. Polysomes had a density of 1.295--1.300 g/cm3 in metrizamide gradients which was also the density of glycogen. However, the polysaccharide reached its equilibrium more rapidly than the polysomes. Thus a short centrifugation of a polysome suspension from non-starved rats over a 40% metrizamide cushion was sufficient to eliminate more than 85% of the glycogen with a polysome yield of about 75%. 2. Ribosomal subunits had neighbouring densities (1.23 and 1.20 g/cm3 for large and small EDTA-derived subunits; 1.23 and 1.21 g/cm3 for large and small KCl/puromycin-derived subunits, respectively). Polysomal messenger ribonucleoproteins were heterogeneously distributed (phi = 1.12 to 1.23 g/cm3) and overlapped with subunits in a similar manner as in sucrose gradients. 3. Analysis of a post-mitochondrial supernatant in metrizamide showed a clear separation of free polysomes, rough membranes and the soluble phase.", "contents": "The use of metrizamide as a density-gradient medium in studies of rat-liver polysomes. The behaviour of rat liver cytoplasmic ribonucleoproteins in metrizamide has been studied to determine whether the iodinated compound would offer any advantage over other centrifugation media for studies of polysome structure and function. 1. Polysomes had a density of 1.295--1.300 g/cm3 in metrizamide gradients which was also the density of glycogen. However, the polysaccharide reached its equilibrium more rapidly than the polysomes. Thus a short centrifugation of a polysome suspension from non-starved rats over a 40% metrizamide cushion was sufficient to eliminate more than 85% of the glycogen with a polysome yield of about 75%. 2. Ribosomal subunits had neighbouring densities (1.23 and 1.20 g/cm3 for large and small EDTA-derived subunits; 1.23 and 1.21 g/cm3 for large and small KCl/puromycin-derived subunits, respectively). Polysomal messenger ribonucleoproteins were heterogeneously distributed (phi = 1.12 to 1.23 g/cm3) and overlapped with subunits in a similar manner as in sucrose gradients. 3. Analysis of a post-mitochondrial supernatant in metrizamide showed a clear separation of free polysomes, rough membranes and the soluble phase."} {"id": "PMID:1278164", "title": "Binding of human hemoglobin and its polypeptide chains with haptoglobin coupled to an agarose matrix.", "content": "The interactions of human haptoglobin covalently linked to agarose with human hemoglobin and with p-chloromercuribenzoic-acid-treated alpha and beta chains (alpha* and beta* chains) were studied by flow chromatography and equilibrium binding. The results indicate that in solid state, haptoglobin maintains the same binding characteristics as in solution, the order of binding affinities being: hemoglobin greater than alpha* chain greater than beta* chain. The study of the binding parameters of the alpha* chain shows an heterogeneity of binding sites on the haptoglobin and an average affinity constant Ka of 3.6 X 10(4)l/mol.", "contents": "Binding of human hemoglobin and its polypeptide chains with haptoglobin coupled to an agarose matrix. The interactions of human haptoglobin covalently linked to agarose with human hemoglobin and with p-chloromercuribenzoic-acid-treated alpha and beta chains (alpha* and beta* chains) were studied by flow chromatography and equilibrium binding. The results indicate that in solid state, haptoglobin maintains the same binding characteristics as in solution, the order of binding affinities being: hemoglobin greater than alpha* chain greater than beta* chain. The study of the binding parameters of the alpha* chain shows an heterogeneity of binding sites on the haptoglobin and an average affinity constant Ka of 3.6 X 10(4)l/mol."} {"id": "PMID:1278165", "title": "Immunochemical detection of the Thomsen-Friedenreich antigen (T-antigen) on the pig lymphocyte plasma membrane.", "content": "A method for the isolation of lymphocytes from pig peripheral blood and preparation of plasma membranes was developed. The method resulted in a ten-fold increase in 5'-nucleotidase activity and neuraminic acid, relative to protein. A cholesterol/phospholipid ratio of 0.93 was obtained. Alkaline borohydride treatment of isolated plasma membrane, after desialylation, released the disaccharide beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol (the immunodominant group of the T-antigen), which was identified by gas chromatography using a crystalline standard. The disaccharide was not found without prior desialylation, indicating that all the disaccharide units were substituted by neuraminic acid. Serological evidence using the agglutinins from Arachis hypogoea and Helix pomatia confirmed the presence of this disaccharide (T-antigen) in the lymphocyte membrane and indicated that it was the major alkali-labile oligosaccharide of the pig lymphocyte membrane.", "contents": "Immunochemical detection of the Thomsen-Friedenreich antigen (T-antigen) on the pig lymphocyte plasma membrane. A method for the isolation of lymphocytes from pig peripheral blood and preparation of plasma membranes was developed. The method resulted in a ten-fold increase in 5'-nucleotidase activity and neuraminic acid, relative to protein. A cholesterol/phospholipid ratio of 0.93 was obtained. Alkaline borohydride treatment of isolated plasma membrane, after desialylation, released the disaccharide beta-D-galactosyl-(1 leads to 3)-N-acetyl-D-galactosaminitol (the immunodominant group of the T-antigen), which was identified by gas chromatography using a crystalline standard. The disaccharide was not found without prior desialylation, indicating that all the disaccharide units were substituted by neuraminic acid. Serological evidence using the agglutinins from Arachis hypogoea and Helix pomatia confirmed the presence of this disaccharide (T-antigen) in the lymphocyte membrane and indicated that it was the major alkali-labile oligosaccharide of the pig lymphocyte membrane."} {"id": "PMID:1278166", "title": "Interaction between membrane functions and protein synthesis in reticulocytes. A membrane constituent which inhibits protein synthesis in cell-free system.", "content": "The reticulocyte cell membrane was investigated for the role that it plays in cellular protein synthesis. It was found that a strong inhibition in protein synthesis occurred when a membranal extract was added to a cell-free protein-synthesizing system. The membranal extract was obtained by disrupting and then sulubilizing cell membranes with the non-ionic detergent Triton X-100. The inhibition in protein synthesis could neither be attributed to an RNAse-type action nor to a reduction in the energy level of the system. Preliminary results show that the principal site of action occurs at the elongation or/and termination stages of protein synthesis. Initial purification of the inhibitory component was achieved.", "contents": "Interaction between membrane functions and protein synthesis in reticulocytes. A membrane constituent which inhibits protein synthesis in cell-free system. The reticulocyte cell membrane was investigated for the role that it plays in cellular protein synthesis. It was found that a strong inhibition in protein synthesis occurred when a membranal extract was added to a cell-free protein-synthesizing system. The membranal extract was obtained by disrupting and then sulubilizing cell membranes with the non-ionic detergent Triton X-100. The inhibition in protein synthesis could neither be attributed to an RNAse-type action nor to a reduction in the energy level of the system. Preliminary results show that the principal site of action occurs at the elongation or/and termination stages of protein synthesis. Initial purification of the inhibitory component was achieved."} {"id": "PMID:1278167", "title": "Determination of molecular weight and molecular structure of rat-liver pyruvate carboxylase.", "content": "The molecular weight of pyruvate carboxylase isolated from pigeon and rat liver mitochondria was examined using analytical ultracentrifugation and electron microscopy. The enzyme molecule appeared as a tetramer with the four subunits arranged at the corners of a square. Sedimentation studies in the analytical ultracentrifuge, extrapolated to infinite dilution, showed the tetramer to have a molecular weight Mc=0r of 280 000 and an So20,w of 12.7 S. The tetramer could be dissociated into trimers and dimers of lower specific enzymic activity by storage at 4 degrees C or incubation at -- 20 degrees C at low protein concentrations. The isolated trimers and dimers had a molecular weight Mc=0r of 210 000 and 140 000, respectively, and an So20,w of 10.85 S and 7.55 S, respectively. Incubation with 2 M urea at 20 degrees C yielded enzymically inactive subunits (Mc=0r = 70 000; So20,w = 4.95 S). The molecular weights (for pyruvate carboxylase and its subunits), as calculated from the subunit diameter observed in the electron microscope, were consistent with the values obtained from sedimentation studies.", "contents": "Determination of molecular weight and molecular structure of rat-liver pyruvate carboxylase. The molecular weight of pyruvate carboxylase isolated from pigeon and rat liver mitochondria was examined using analytical ultracentrifugation and electron microscopy. The enzyme molecule appeared as a tetramer with the four subunits arranged at the corners of a square. Sedimentation studies in the analytical ultracentrifuge, extrapolated to infinite dilution, showed the tetramer to have a molecular weight Mc=0r of 280 000 and an So20,w of 12.7 S. The tetramer could be dissociated into trimers and dimers of lower specific enzymic activity by storage at 4 degrees C or incubation at -- 20 degrees C at low protein concentrations. The isolated trimers and dimers had a molecular weight Mc=0r of 210 000 and 140 000, respectively, and an So20,w of 10.85 S and 7.55 S, respectively. Incubation with 2 M urea at 20 degrees C yielded enzymically inactive subunits (Mc=0r = 70 000; So20,w = 4.95 S). The molecular weights (for pyruvate carboxylase and its subunits), as calculated from the subunit diameter observed in the electron microscope, were consistent with the values obtained from sedimentation studies."} {"id": "PMID:1278168", "title": "Absolute configuration of 3-hydroxy fatty acids present in lipopolysaccharides from various bacterial groups.", "content": "The absolute configuration of 3-hydroxy fatty acids has been studied, which are present in the lipopolysaccharides of the following bacteria: Phodopseudomonas gelatinosa, Rh. viridis, Rhodospirillum tenue, Chromobacterium violaceum, Pseudomonas aeruginosa, Bordetella pertussis, Vibrio metchnikovii, Vibrio cholerae, Salmonella spp., Escherichia coli, Shigella flexneri, Proteus mirabilis, Yersinia enterocolitica and Fusobacterium nucleatum. The 3-hydroxy acids were liberated by strong alkaline hydrolysis, converted to 3-methoxy acid L-phenylethylamides and analyzed by gas-liquid chromatography. With the aid of authentic D-3-hydroxy fatty acids it was shown for all lipopolysaccharides that the 3-hydroxy acids, regardless of chain lengths, branching, 3-O-substitution or type of linkage, possess the D-configuration. 2-Hydroxydodecanoic acid, which is present in some lipopolysaccharides, was analyzed in an analogous way and shown to possess the L-configuration.", "contents": "Absolute configuration of 3-hydroxy fatty acids present in lipopolysaccharides from various bacterial groups. The absolute configuration of 3-hydroxy fatty acids has been studied, which are present in the lipopolysaccharides of the following bacteria: Phodopseudomonas gelatinosa, Rh. viridis, Rhodospirillum tenue, Chromobacterium violaceum, Pseudomonas aeruginosa, Bordetella pertussis, Vibrio metchnikovii, Vibrio cholerae, Salmonella spp., Escherichia coli, Shigella flexneri, Proteus mirabilis, Yersinia enterocolitica and Fusobacterium nucleatum. The 3-hydroxy acids were liberated by strong alkaline hydrolysis, converted to 3-methoxy acid L-phenylethylamides and analyzed by gas-liquid chromatography. With the aid of authentic D-3-hydroxy fatty acids it was shown for all lipopolysaccharides that the 3-hydroxy acids, regardless of chain lengths, branching, 3-O-substitution or type of linkage, possess the D-configuration. 2-Hydroxydodecanoic acid, which is present in some lipopolysaccharides, was analyzed in an analogous way and shown to possess the L-configuration."} {"id": "PMID:1278169", "title": "Protective effect of elongation factor 2 on the inactivation of ribosomes by the toxic lectins abrin and ricin.", "content": "The inactivation of rabbit reticulocyte ribosomes by abrin and ricin A-chains was studied by incubating ribosomes with the A-chains and testing, after various periods of time, aliquots of the ribosomes for their ability to polymerize phenylalanine. The presence of elongation factor 2 (EF-2) reduced the rate of inactivation of ribosomes by the A-chains. The protective effect of EF-2 was strongly enhanced by GTP and, to a lesser extent, also by GDP or dGTP. Other nucleotides had no demonstrable effect. Much less protection was found after binding of Phe-tRNA to ribosomes in the presence of EF-1 (enzymic binding) or in the presence of high Mg2+ concentration (non-enzymic binding). The data indicate that when EF-2 binds to the ribosomes it completely or partially covers the target site for abrin and ricin A-chains. The possibility that EF-1 also binds to this site is discussed.", "contents": "Protective effect of elongation factor 2 on the inactivation of ribosomes by the toxic lectins abrin and ricin. The inactivation of rabbit reticulocyte ribosomes by abrin and ricin A-chains was studied by incubating ribosomes with the A-chains and testing, after various periods of time, aliquots of the ribosomes for their ability to polymerize phenylalanine. The presence of elongation factor 2 (EF-2) reduced the rate of inactivation of ribosomes by the A-chains. The protective effect of EF-2 was strongly enhanced by GTP and, to a lesser extent, also by GDP or dGTP. Other nucleotides had no demonstrable effect. Much less protection was found after binding of Phe-tRNA to ribosomes in the presence of EF-1 (enzymic binding) or in the presence of high Mg2+ concentration (non-enzymic binding). The data indicate that when EF-2 binds to the ribosomes it completely or partially covers the target site for abrin and ricin A-chains. The possibility that EF-1 also binds to this site is discussed."} {"id": "PMID:1278170", "title": "Variable stabilities and recoveries of rat-liver RNA polymerases A and B according to growth status of the tissue.", "content": "1. The effect of growth status on the relative levels and recoveries of DNA-dependent RNA polymerase in rat liver nuclei was determined by two independent procedures: (a) measurement of RNA polymerase A and B activities in fraction IV [Roeder, R. G. and Rutter, W. J. (1970) Proc. Natl Acad. Sci. U.S.A. 65, 675--682] in the presence and absence of low concentrations of alpha-amanitin; (b) DEAE-Sephadex chromatography of fraction IV to resolve RNA polymerases A and B (and possibly other forms of the enzyme). 2. Growth was arrested in young rats (less than 100 g body weight) by hypophysectomy and stimulated by the administration of growth hormone or triiodothyronine. Under these conditions the rate of RNA synthesis in vivo or in isolated nuclei is known to be markedly depressed or stimulated relatively soon after hypophysectomy or hormone administration, respectively. RNA polymerases were obtained from animals under different growth conditions. There were no differences in the activities of nuclear RNA ploymerases per se, when these were separated from their endogenous template and assayed with heterologous denatured DNA. These reports contrast with earlier reports [Smuckler, E. A. and Tata, J. R. (1971) Nat. New Biol. 234, 37--39; Sajdel, E. M. and Jacob, S. T. (1971) Biochem. Biophys. Res. Commun. 45, 707--715]. 3. The discrepancy was resolved when a 'balance sheet' of enzyme recovery was established. Cessation of growth by hypophysectomy led to a marked reduction in the recovery of both forms A and B of the enzyme (less than 20% of the input RNA polymerase activity in fraction iv) following chromatography on DEAE-Sephadex. This effect was reversed within a short time after the administration of growth hormone (3--9 h) or triiodothyronine (18--24 h), leading to a doubling of the enzyme recoveries. These alterations which were more marked for RNA polymerase A, resulted in different elution profiles for RNA polymerases A and B upon chromatography. 4. It is concluded that the use of DEAE-Sephadex chromatography to compare the levels of RNA polymerases A and B isolated from tissues of different growth rate can give rise to over-estimates of apparent changes in their relative activities and that the measurement of enzyme activity in fraction IV is a better index of RNA polymerase levels. The relationship between growth rate of cells, the stability of RNA polymerases, and the importance of determining enzyme recoveries upon chromatography, are discussed.", "contents": "Variable stabilities and recoveries of rat-liver RNA polymerases A and B according to growth status of the tissue. 1. The effect of growth status on the relative levels and recoveries of DNA-dependent RNA polymerase in rat liver nuclei was determined by two independent procedures: (a) measurement of RNA polymerase A and B activities in fraction IV [Roeder, R. G. and Rutter, W. J. (1970) Proc. Natl Acad. Sci. U.S.A. 65, 675--682] in the presence and absence of low concentrations of alpha-amanitin; (b) DEAE-Sephadex chromatography of fraction IV to resolve RNA polymerases A and B (and possibly other forms of the enzyme). 2. Growth was arrested in young rats (less than 100 g body weight) by hypophysectomy and stimulated by the administration of growth hormone or triiodothyronine. Under these conditions the rate of RNA synthesis in vivo or in isolated nuclei is known to be markedly depressed or stimulated relatively soon after hypophysectomy or hormone administration, respectively. RNA polymerases were obtained from animals under different growth conditions. There were no differences in the activities of nuclear RNA ploymerases per se, when these were separated from their endogenous template and assayed with heterologous denatured DNA. These reports contrast with earlier reports [Smuckler, E. A. and Tata, J. R. (1971) Nat. New Biol. 234, 37--39; Sajdel, E. M. and Jacob, S. T. (1971) Biochem. Biophys. Res. Commun. 45, 707--715]. 3. The discrepancy was resolved when a 'balance sheet' of enzyme recovery was established. Cessation of growth by hypophysectomy led to a marked reduction in the recovery of both forms A and B of the enzyme (less than 20% of the input RNA polymerase activity in fraction iv) following chromatography on DEAE-Sephadex. This effect was reversed within a short time after the administration of growth hormone (3--9 h) or triiodothyronine (18--24 h), leading to a doubling of the enzyme recoveries. These alterations which were more marked for RNA polymerase A, resulted in different elution profiles for RNA polymerases A and B upon chromatography. 4. It is concluded that the use of DEAE-Sephadex chromatography to compare the levels of RNA polymerases A and B isolated from tissues of different growth rate can give rise to over-estimates of apparent changes in their relative activities and that the measurement of enzyme activity in fraction IV is a better index of RNA polymerase levels. The relationship between growth rate of cells, the stability of RNA polymerases, and the importance of determining enzyme recoveries upon chromatography, are discussed."} {"id": "PMID:1278171", "title": "Large-scale purification and some properties of the mitochondrial aspartate aminotransferase from pig heart.", "content": "A method has been developed which allows isolation of 0.3--0.5 g of mitochondrial aspartate aminotransferase in five days starting from 10 pig hearts; the method does not involve initial preparation of mitochondria. Mitochondrial malate dehydrogenase and the cytoplasmic aspartate aminotransferase may conveniently be recovered from side fractions. The product mitochondrial aspartate aminotransferase is homogeneous as judged by various electrophoretic techniques and by N-terminal analysis. Crystals of the enzyme have been obtained both from concentrated, essentially salt-free, solutions and from solutions of ammonium sulphate. The amino acid composition, N and C-terminal amino acid sequences and subunit molecular weight have been determined; these characteristic properties are compared with those of the cytoplasmic isozyme from the same source.", "contents": "Large-scale purification and some properties of the mitochondrial aspartate aminotransferase from pig heart. A method has been developed which allows isolation of 0.3--0.5 g of mitochondrial aspartate aminotransferase in five days starting from 10 pig hearts; the method does not involve initial preparation of mitochondria. Mitochondrial malate dehydrogenase and the cytoplasmic aspartate aminotransferase may conveniently be recovered from side fractions. The product mitochondrial aspartate aminotransferase is homogeneous as judged by various electrophoretic techniques and by N-terminal analysis. Crystals of the enzyme have been obtained both from concentrated, essentially salt-free, solutions and from solutions of ammonium sulphate. The amino acid composition, N and C-terminal amino acid sequences and subunit molecular weight have been determined; these characteristic properties are compared with those of the cytoplasmic isozyme from the same source."} {"id": "PMID:1278172", "title": "Separate pyrimidine-nucleotide pools for messenger-RNA and ribosomal-RNA synthesis in HeLa S3 cells.", "content": "Kinetic analyses of mRNA and 28-S RNA labeling [3H]uridine revealed distinctly different steady-state specific radioactivities finally reached for uridine in mRNA and 28-S RNA when exogenous [3H]uridine was kept constant for several cell doubling times. While the steady-state label of (total) UTP and of uridine in mRNA responded to the same extent to a suppression of pyrimidine synthesis de novo by high uridine concentrations in the culture medium, uridine in 28-S RNA was scarcely influenced. Similar findings were obtained with respect to labeling of cytidine in the various RNA species due to an equilibration of UTP with CTP [5-3H]Uridine is also incorporated into deoxycytidine of DNA, presumably via dCTP. The specific radioactivity of this nucleosidase attained the same steady-state value as UTP, uridine in mRNA and cytidine in mRNA. The data indicate the existence of two pyrimidine nucleotide pools. One is a large, general UTP pool comprising the bulk of the cellular UTP and serving nucleoplasmic nucleic acid formation (uridine and cytidine in mRNA, deoxycytidine in DNA). Its replenishment by de novo synthesis can be suppressed completely by exogenous uridine above 100 muM concentrations. A second, very small UTP (and CTP) pool with a high turnover provides most of the precursors for nucleolar RNA formation (rRNA). This pool is not subject to feedback inhibition by extracellular uridine to an appreciable extent. Determinations of (total) UTP turnover also show that the bulk of cellular RNA (rRNA) cannot be derived from the large UTP pool.", "contents": "Separate pyrimidine-nucleotide pools for messenger-RNA and ribosomal-RNA synthesis in HeLa S3 cells. Kinetic analyses of mRNA and 28-S RNA labeling [3H]uridine revealed distinctly different steady-state specific radioactivities finally reached for uridine in mRNA and 28-S RNA when exogenous [3H]uridine was kept constant for several cell doubling times. While the steady-state label of (total) UTP and of uridine in mRNA responded to the same extent to a suppression of pyrimidine synthesis de novo by high uridine concentrations in the culture medium, uridine in 28-S RNA was scarcely influenced. Similar findings were obtained with respect to labeling of cytidine in the various RNA species due to an equilibration of UTP with CTP [5-3H]Uridine is also incorporated into deoxycytidine of DNA, presumably via dCTP. The specific radioactivity of this nucleosidase attained the same steady-state value as UTP, uridine in mRNA and cytidine in mRNA. The data indicate the existence of two pyrimidine nucleotide pools. One is a large, general UTP pool comprising the bulk of the cellular UTP and serving nucleoplasmic nucleic acid formation (uridine and cytidine in mRNA, deoxycytidine in DNA). Its replenishment by de novo synthesis can be suppressed completely by exogenous uridine above 100 muM concentrations. A second, very small UTP (and CTP) pool with a high turnover provides most of the precursors for nucleolar RNA formation (rRNA). This pool is not subject to feedback inhibition by extracellular uridine to an appreciable extent. Determinations of (total) UTP turnover also show that the bulk of cellular RNA (rRNA) cannot be derived from the large UTP pool."} {"id": "PMID:1278173", "title": "Coordinated action of pectinesterase and polygalacturonate lyase complex of Clostridium multifermentans.", "content": "The polygalacturonate lyase and pectinesterase activities of Clostridium multifermentans, both produced extracellularly when the organism grows on pectin or polygalacturonate, have been suggested to be associated in a single complex. Both enzymic sites act on their respective substrates by single-chain action patterns, as shown by equivalent release of terminal tritium label and total product throughout the reaction. From these results, the Km and V of the lyase, and the amount of lyase activity present, we calculate the steady-state concentration of lyase substrate expected during action of the two sites on pectin if the sites are independent. No such steady-state concentration of lyase substrate was observed. Therefore, we conclude that the two types of active site act in a coordinated manner; the polysaccharide chain passes from the esterase site to the lyase site without intermediate dissociation and rebinding. This 'molecular disassembly line' constituted by the two sites may represent a system of general significance in synthesis and degradation of biological polymers.", "contents": "Coordinated action of pectinesterase and polygalacturonate lyase complex of Clostridium multifermentans. The polygalacturonate lyase and pectinesterase activities of Clostridium multifermentans, both produced extracellularly when the organism grows on pectin or polygalacturonate, have been suggested to be associated in a single complex. Both enzymic sites act on their respective substrates by single-chain action patterns, as shown by equivalent release of terminal tritium label and total product throughout the reaction. From these results, the Km and V of the lyase, and the amount of lyase activity present, we calculate the steady-state concentration of lyase substrate expected during action of the two sites on pectin if the sites are independent. No such steady-state concentration of lyase substrate was observed. Therefore, we conclude that the two types of active site act in a coordinated manner; the polysaccharide chain passes from the esterase site to the lyase site without intermediate dissociation and rebinding. This 'molecular disassembly line' constituted by the two sites may represent a system of general significance in synthesis and degradation of biological polymers."} {"id": "PMID:1278174", "title": "Hepatic 15-hydroxylation of corticosteroids in the rat. Substrate specificity studied in the isolated perfused liver.", "content": "The substrate specificity of a sex-specific hepatic 15-hydroxylase active on different C21O2 and C21O3 steroids was studied in the isolated perfused liver from female rats. Liquid-chromatographic separation methods in combination with computerized gas chromatography-mass spectrometry was employed to identify the metabolites formed. The majority (between 75-90%) of 15-hydroxylated compounds isolated were present as monosulphate conjugates while smaller amounts of disulphates were also detected. Hydroxylation was found to take place exclusively at position 15 beta. A certain number of 11-deoxy-21-hydroxy, 11-oxo-21-hydroxy and 11,21-dihydroxy steroids with a 3-keto-delta4-, 3-keto-5 alpha(5 beta)-, 3alpha, 5alpha- or 3 beta, 5 beta-structure were readily converted to 15 beta-hydroxylated metabolites. Depending on the structure of the substrate, between 20 and 87% of the total metabolites formed were 15 beta-hydroxylated. 5 alpha-Reduced steroids were better substrates for the hydroxylase than the corresponding 3-keto-delta4- or 5 beta-reduced compounds. The configuration of the hydroxylgroup at C-3 did not affect the degree of 15-hydroxylation. 11 beta-Hydroxylated steroids served as better substrates than the corresponding 11-dehydro-, 11-deoxy- or 11 alpha-hydroxy compounds. 5 alpha-Dihydrocorticosterone and 3 alpha, 5 alpha-tetrahydrocorticosterone were the best substrates for the 15 beta-hydroxylase.", "contents": "Hepatic 15-hydroxylation of corticosteroids in the rat. Substrate specificity studied in the isolated perfused liver. The substrate specificity of a sex-specific hepatic 15-hydroxylase active on different C21O2 and C21O3 steroids was studied in the isolated perfused liver from female rats. Liquid-chromatographic separation methods in combination with computerized gas chromatography-mass spectrometry was employed to identify the metabolites formed. The majority (between 75-90%) of 15-hydroxylated compounds isolated were present as monosulphate conjugates while smaller amounts of disulphates were also detected. Hydroxylation was found to take place exclusively at position 15 beta. A certain number of 11-deoxy-21-hydroxy, 11-oxo-21-hydroxy and 11,21-dihydroxy steroids with a 3-keto-delta4-, 3-keto-5 alpha(5 beta)-, 3alpha, 5alpha- or 3 beta, 5 beta-structure were readily converted to 15 beta-hydroxylated metabolites. Depending on the structure of the substrate, between 20 and 87% of the total metabolites formed were 15 beta-hydroxylated. 5 alpha-Reduced steroids were better substrates for the hydroxylase than the corresponding 3-keto-delta4- or 5 beta-reduced compounds. The configuration of the hydroxylgroup at C-3 did not affect the degree of 15-hydroxylation. 11 beta-Hydroxylated steroids served as better substrates than the corresponding 11-dehydro-, 11-deoxy- or 11 alpha-hydroxy compounds. 5 alpha-Dihydrocorticosterone and 3 alpha, 5 alpha-tetrahydrocorticosterone were the best substrates for the 15 beta-hydroxylase."} {"id": "PMID:1278175", "title": "The complete amino-acid sequence of rat thyrocalcitonin.", "content": "The complete amino acid sequence of rat thyrocalcitonin has been determined by automated Edman degradations of the intact molecule, a cyanogen bromide fragment, and by degradations of mixtures of peptides produced by hydrolysis of the hormone with trypsin and chymotrypsin. The sequence determined was H2N-Cys-Gly-Asn-Leu-Ser-Thr-Cys-Met-Leu-Gly-Thr-Tyr-Thr-Gln-Asp-Leu-Asn-Lys-Phe-His-Thr-Phe-Pro-Gln-Thr-Ser-Ile-Gly-Val-Gly-Ala-Pro-NH2. This sequence differs in only two positions from that found in the human hormone, i.e. leucine-16 in the rat vs phenylalanine-16 in the human, and serine-26 in the rat vs alanine-26 in the human. These similarities and differences are consistent with the previously reported immunological properties of the hormones isolated from these two species.", "contents": "The complete amino-acid sequence of rat thyrocalcitonin. The complete amino acid sequence of rat thyrocalcitonin has been determined by automated Edman degradations of the intact molecule, a cyanogen bromide fragment, and by degradations of mixtures of peptides produced by hydrolysis of the hormone with trypsin and chymotrypsin. The sequence determined was H2N-Cys-Gly-Asn-Leu-Ser-Thr-Cys-Met-Leu-Gly-Thr-Tyr-Thr-Gln-Asp-Leu-Asn-Lys-Phe-His-Thr-Phe-Pro-Gln-Thr-Ser-Ile-Gly-Val-Gly-Ala-Pro-NH2. This sequence differs in only two positions from that found in the human hormone, i.e. leucine-16 in the rat vs phenylalanine-16 in the human, and serine-26 in the rat vs alanine-26 in the human. These similarities and differences are consistent with the previously reported immunological properties of the hormones isolated from these two species."} {"id": "PMID:1278176", "title": "Partial characterization of hog renin purified by affinity chromatography.", "content": "A method has been set up to purify renin on a large scale by affinity chromatography using Pepstatin, a potent inhibitor of renin, as a ligand. Pepstatin was covalently coupled to Sepharose via six different spacer 'arms'. The Sepharose-hexamethylenediamino-Pepstatin appeared to be the better derivative for renin purification even at a concentration as low as 160 nmol of Pepstatin/ml of moist gel. Renin was extracted from 100 kg of hog kidneys and semi-purified by ammonium sulfate precipitations and chromatography on DEAE-cellulose. The active fraction (48.5 g of proteins) was applied on a 500-ml affinity column. Renin was eluted in the starting buffer containing 6 M urea. Renin was purified 120-fold by the affinity chromatography step with a 79% recovery. Physico-chemical characterization of highly purified renin was performed. Isoelectrofocusing on a pH gradient from 3 to 6 showed a major peak with an isoelectric point (pI) of 4.95 and a minor peak (pI = 4.70). Polyacrylamide gel electrophoresis, pH 7.8, at different gel concentrations, showed a single peak of renin activity which was found in the major protein band. Molecular size estimated on agarose-acrylamide gel filtration was 40 000. All these physical parameters were similar before and after purification.", "contents": "Partial characterization of hog renin purified by affinity chromatography. A method has been set up to purify renin on a large scale by affinity chromatography using Pepstatin, a potent inhibitor of renin, as a ligand. Pepstatin was covalently coupled to Sepharose via six different spacer 'arms'. The Sepharose-hexamethylenediamino-Pepstatin appeared to be the better derivative for renin purification even at a concentration as low as 160 nmol of Pepstatin/ml of moist gel. Renin was extracted from 100 kg of hog kidneys and semi-purified by ammonium sulfate precipitations and chromatography on DEAE-cellulose. The active fraction (48.5 g of proteins) was applied on a 500-ml affinity column. Renin was eluted in the starting buffer containing 6 M urea. Renin was purified 120-fold by the affinity chromatography step with a 79% recovery. Physico-chemical characterization of highly purified renin was performed. Isoelectrofocusing on a pH gradient from 3 to 6 showed a major peak with an isoelectric point (pI) of 4.95 and a minor peak (pI = 4.70). Polyacrylamide gel electrophoresis, pH 7.8, at different gel concentrations, showed a single peak of renin activity which was found in the major protein band. Molecular size estimated on agarose-acrylamide gel filtration was 40 000. All these physical parameters were similar before and after purification."} {"id": "PMID:1278179", "title": "Enzymic generation of chiral acetates. A quantitative evaluation of their configurational assay.", "content": "1. R-Acetate was generated enzymically from R-acetate in the sequence acetate leads to malate leads to oxaloacetate leads to acetate, and S-acetate likewise from S-acetate. It was concluded that the formation of malate on malate synthase involves the operation of a normal isotopic effect combined with inversion of configuration. The malate synthase kH/k2H was determined as 3.7 +/- 0.5 by a method which yields results independently of the stereochemical purity of the chiral acetates used initially. 2. R-Acetate was also generated from R-acetate in the sequence acetate leads to citrate leads to malate leads to oxaloacetate leads to acetate, and S-acetate likewise from S-acetate. The conclusion is the same as given above, but refers to the formation of citrate on the re-synthase. 3. 2S,3R-[2-2H1,3-2H1,3H1]Malate and 2S,3S-[2-2H1,3-2H1]malate were prepared from 2S-[2,3-2H3]malate by treatment with fumarase in tritiated water and normal water, respectively. It was assumed that these malate specimens were pure with respect to chirality as generated by isotopic labelling. 4. These two malate specimens were partially converted (about 9%) to acetates in conditions where no racemization at the level of transiently formed oxaloacetate occurred. That no racemization took place was demonstrated experimentally. Oxidative enzymic hydrolysis of 2S,3R-[2-2H1,3-2H1,3H1]malate in normal water and of 2S,3S-[2-2H1,3-2H1]malate in tritiated water produced S-[2H1,3H1]acetate and R-[2H1,3H1]acetate, respectively. 5. The isolated R-[2H1,3H1]acetate and S-[2H1,3H1]acetate on configurational analysis yielded malates which in the presence of fumarase retained 79.7 +/- 0.7% and 20.3 +/- 0.9%, respectively, of their total tritium content. The symmetric deviation from the 50% value found with [3H1]acetate strengthens the conclusion that stereochemically pure chiral acetates were analyzed. The malate synthase kH/k2H was determined from the data of this study as 3.9 +/- 0.2. 6. The average of the values given under paragraphs 1 and 5 for the isotopic discrimination on malate synthase corresponds to kH/k2H=3.8 +/- 0.1. It was concluded that the configurational analysis of stereochemically pure R-[2H1,3H1]acetate and S-[2H1,3H1]acetate yields malates which in the presence of fumarase retain 79 +/- 2% and 21 +/- 2%, respectively, of their total tritium content. Hence, a deviation of 29 +/- 2% from the 50% value represents the actual amplitude of the configurational assay. 7. Outlines are given for an enzymic generation of chiral acetates in preparative scale.", "contents": "Enzymic generation of chiral acetates. A quantitative evaluation of their configurational assay. 1. R-Acetate was generated enzymically from R-acetate in the sequence acetate leads to malate leads to oxaloacetate leads to acetate, and S-acetate likewise from S-acetate. It was concluded that the formation of malate on malate synthase involves the operation of a normal isotopic effect combined with inversion of configuration. The malate synthase kH/k2H was determined as 3.7 +/- 0.5 by a method which yields results independently of the stereochemical purity of the chiral acetates used initially. 2. R-Acetate was also generated from R-acetate in the sequence acetate leads to citrate leads to malate leads to oxaloacetate leads to acetate, and S-acetate likewise from S-acetate. The conclusion is the same as given above, but refers to the formation of citrate on the re-synthase. 3. 2S,3R-[2-2H1,3-2H1,3H1]Malate and 2S,3S-[2-2H1,3-2H1]malate were prepared from 2S-[2,3-2H3]malate by treatment with fumarase in tritiated water and normal water, respectively. It was assumed that these malate specimens were pure with respect to chirality as generated by isotopic labelling. 4. These two malate specimens were partially converted (about 9%) to acetates in conditions where no racemization at the level of transiently formed oxaloacetate occurred. That no racemization took place was demonstrated experimentally. Oxidative enzymic hydrolysis of 2S,3R-[2-2H1,3-2H1,3H1]malate in normal water and of 2S,3S-[2-2H1,3-2H1]malate in tritiated water produced S-[2H1,3H1]acetate and R-[2H1,3H1]acetate, respectively. 5. The isolated R-[2H1,3H1]acetate and S-[2H1,3H1]acetate on configurational analysis yielded malates which in the presence of fumarase retained 79.7 +/- 0.7% and 20.3 +/- 0.9%, respectively, of their total tritium content. The symmetric deviation from the 50% value found with [3H1]acetate strengthens the conclusion that stereochemically pure chiral acetates were analyzed. The malate synthase kH/k2H was determined from the data of this study as 3.9 +/- 0.2. 6. The average of the values given under paragraphs 1 and 5 for the isotopic discrimination on malate synthase corresponds to kH/k2H=3.8 +/- 0.1. It was concluded that the configurational analysis of stereochemically pure R-[2H1,3H1]acetate and S-[2H1,3H1]acetate yields malates which in the presence of fumarase retain 79 +/- 2% and 21 +/- 2%, respectively, of their total tritium content. Hence, a deviation of 29 +/- 2% from the 50% value represents the actual amplitude of the configurational assay. 7. Outlines are given for an enzymic generation of chiral acetates in preparative scale."} {"id": "PMID:1278181", "title": "Glutamine transaminase from brain tissue. Further studies on kinetic properties and specificity of the enzyme.", "content": "Glutamine transaminase, highly purified from rat brain, was studied. In the first series of experiments, the kinetics of the transamination reaction between 2-oxoglutaramate and phenylalanine were examined in order to determine the type of reaction mechanism. This proved to be of the ping-pont type, as can be expected for a transamination. The specificity of the enzyme for various amino acids and 2-oxo acids was then studied in detail. The most active substrates were glutamine, methionine and ethionine as amino-group donors, and phenylpyruvate, glyoxalate and 2-oxo-4-methiobutyrate as amino-group acceptors. For these and several other substrates, the kinetic constants, V and Km, were determined.", "contents": "Glutamine transaminase from brain tissue. Further studies on kinetic properties and specificity of the enzyme. Glutamine transaminase, highly purified from rat brain, was studied. In the first series of experiments, the kinetics of the transamination reaction between 2-oxoglutaramate and phenylalanine were examined in order to determine the type of reaction mechanism. This proved to be of the ping-pont type, as can be expected for a transamination. The specificity of the enzyme for various amino acids and 2-oxo acids was then studied in detail. The most active substrates were glutamine, methionine and ethionine as amino-group donors, and phenylpyruvate, glyoxalate and 2-oxo-4-methiobutyrate as amino-group acceptors. For these and several other substrates, the kinetic constants, V and Km, were determined."} {"id": "PMID:1278182", "title": "Complementation of subunits from glycogen phosphorylases of frog and rabbit skeletal muscle and rabbit liver.", "content": "Activity can be induced in potentially active rabbit skeletal muscle phosphorylase monomers covalently bound to Sepharose by noncovalent interaction with soluble subunits carrying inactive pyridoxal 5'-phosphate analogs or even salicyladlehyde. These analogs are themselves incapable of reconstituting active holophorphorylase from apophosphorylase. Phosphorylases with one intrinsically inactive and one potentially active subunit have about one half of the activity of the native phosphorylase dimer. The usefulness of this technique for subunit complementation was demonstrated by forming hybrid phosphorylases with inactive Sepharose-bound rabbit skeletal muscle subunits containing pyridoxal 5'-phosphate monomethylester and soluble activatable frog muscle and rabbit liver phosphorylase monomers. The inactive Sepharose-bound subunit induced in each case activity in the soluble subunit. But whereas the inactive rabbit muscle phosphorylase subunit even transmitted its characteristic temperature dependence of the rate of the reaction to the frog muscle subunit, it could not propagate its control properties to the liver enzyme. Differences of hybrid phosphorylases are related to immunological and amino acid divergencies among the component enzymes.", "contents": "Complementation of subunits from glycogen phosphorylases of frog and rabbit skeletal muscle and rabbit liver. Activity can be induced in potentially active rabbit skeletal muscle phosphorylase monomers covalently bound to Sepharose by noncovalent interaction with soluble subunits carrying inactive pyridoxal 5'-phosphate analogs or even salicyladlehyde. These analogs are themselves incapable of reconstituting active holophorphorylase from apophosphorylase. Phosphorylases with one intrinsically inactive and one potentially active subunit have about one half of the activity of the native phosphorylase dimer. The usefulness of this technique for subunit complementation was demonstrated by forming hybrid phosphorylases with inactive Sepharose-bound rabbit skeletal muscle subunits containing pyridoxal 5'-phosphate monomethylester and soluble activatable frog muscle and rabbit liver phosphorylase monomers. The inactive Sepharose-bound subunit induced in each case activity in the soluble subunit. But whereas the inactive rabbit muscle phosphorylase subunit even transmitted its characteristic temperature dependence of the rate of the reaction to the frog muscle subunit, it could not propagate its control properties to the liver enzyme. Differences of hybrid phosphorylases are related to immunological and amino acid divergencies among the component enzymes."} {"id": "PMID:1278183", "title": "Cooperative binding of concanavalin A to thymocytes at 4 degrees C and micro-redistribution of concanavalin A receptors.", "content": "The mode of binding of 125I-labelled concanavalin A and succinyl-concanavalin A to rat thymocytes at 4 degrees C was investigated. Simultaneously, the free binding sites of the cell-bound lectin molecules were quantified by horseradish peroxidase binding. Concanavalin A showed cooperative binding while succinyl-concanavalin A did not. The number of molecules of concanavalin A bound to the cell surface when it was saturated was twice the number of molecules of succinyl-concanavalin A. We interpret these results as showing that the binding of native concanavalin A to thymocytes at 4 degrees C brings about a cooperative modification of the membrane which leads to appearance of new receptors. Divalent succinyl-concanavalin A has no such effect. Horseradish peroxidase binding to cell-bound lectin was shown to be related to the immobilization of membrane receptors; the more they are immobilized, the more receptor-associated lectin can bind horseradish peroxidase. This allowed us to establish that post-binding events, which we called micro-redistribution, occurred at 4 degrees C when either concanavalin A or succinyl-concanavalin A binds to cells. A cooperative restriction of the micromobility of cell receptors is produced by increasing concentrations of concanavalin A. Succinyl-concanavalin A does not restrict cell receptor mobility at any concentration tested. The results are discussed in terms of cell stimulation and cell agglutination.", "contents": "Cooperative binding of concanavalin A to thymocytes at 4 degrees C and micro-redistribution of concanavalin A receptors. The mode of binding of 125I-labelled concanavalin A and succinyl-concanavalin A to rat thymocytes at 4 degrees C was investigated. Simultaneously, the free binding sites of the cell-bound lectin molecules were quantified by horseradish peroxidase binding. Concanavalin A showed cooperative binding while succinyl-concanavalin A did not. The number of molecules of concanavalin A bound to the cell surface when it was saturated was twice the number of molecules of succinyl-concanavalin A. We interpret these results as showing that the binding of native concanavalin A to thymocytes at 4 degrees C brings about a cooperative modification of the membrane which leads to appearance of new receptors. Divalent succinyl-concanavalin A has no such effect. Horseradish peroxidase binding to cell-bound lectin was shown to be related to the immobilization of membrane receptors; the more they are immobilized, the more receptor-associated lectin can bind horseradish peroxidase. This allowed us to establish that post-binding events, which we called micro-redistribution, occurred at 4 degrees C when either concanavalin A or succinyl-concanavalin A binds to cells. A cooperative restriction of the micromobility of cell receptors is produced by increasing concentrations of concanavalin A. Succinyl-concanavalin A does not restrict cell receptor mobility at any concentration tested. The results are discussed in terms of cell stimulation and cell agglutination."} {"id": "PMID:1278184", "title": "Acrodermatitis enteropathica: recent findings concerning clinical features, pathogenesis, diagnosis and therapy.", "content": "Acrodermatitis enteropathica (AE) was diagnosed in 2 siblings, boy and girl, at the age of 10 and 6 weeks. The family history is unremarkable except for consanguinity 5 generations previously. The clinical symptoms of the 2 patients conformed to the known features of AE, the gastrointestinal involvement loosing its significance with increasing age. In one patient in a stage of exacerbation the serum level of oleic acid (18:1) was lowered and of linoleic (18:2) acid slightly increased while that of arachidonic acid was decreased (Fig. 4). In both patients the serum zinc levels were significantly lowered. Under substitution with ZnSO4 the clinical condition improved and the serum zinc levels returned to normal. Histologically the small bowel mucosa was practically normal. Ultrastructural examination of jejunal biopsies revealed rather unspecific changes in the enterocytes in the form of numerous multivesicular bodies. The Paneth cells sometimes contained irregularly formed inhomogeneous structures within their cytoplasm. In addition the secretory granules varied in size and displayed a granular heteromorphic matrix. Frequently they were confluent and formed giant granules.", "contents": "Acrodermatitis enteropathica: recent findings concerning clinical features, pathogenesis, diagnosis and therapy. Acrodermatitis enteropathica (AE) was diagnosed in 2 siblings, boy and girl, at the age of 10 and 6 weeks. The family history is unremarkable except for consanguinity 5 generations previously. The clinical symptoms of the 2 patients conformed to the known features of AE, the gastrointestinal involvement loosing its significance with increasing age. In one patient in a stage of exacerbation the serum level of oleic acid (18:1) was lowered and of linoleic (18:2) acid slightly increased while that of arachidonic acid was decreased (Fig. 4). In both patients the serum zinc levels were significantly lowered. Under substitution with ZnSO4 the clinical condition improved and the serum zinc levels returned to normal. Histologically the small bowel mucosa was practically normal. Ultrastructural examination of jejunal biopsies revealed rather unspecific changes in the enterocytes in the form of numerous multivesicular bodies. The Paneth cells sometimes contained irregularly formed inhomogeneous structures within their cytoplasm. In addition the secretory granules varied in size and displayed a granular heteromorphic matrix. Frequently they were confluent and formed giant granules."} {"id": "PMID:1278185", "title": "[Intestinal disaccharidase and alkaline phosphatase activities of jejunal biopsies in small bowel diseases of children (author's transl)].", "content": "Intestinal disaccharidase activities were determined in 294 jejunal biopsies obtained from 254 children with various disorders of the small bowel, and alkaline phosphatase activity was measured in 251 biopsies. In normal mucosa a broad range of enzyme activity was found corresponding with the data in the literature. A primary disaccharidase deficiency was observed in 5 children with congenital sucrase-isomaltase deficiency and in a 12-year-old Egyptian boy with acquired lactase deficiency. A secondary generalized depression of disaccharidase activity and a diminution of alkaline phosphatase activity existed chiefly in patients who had severe or moderate mucosal damage, also in active coeliac disease and during gluten loading, in protracted diarrhoea of infancy, chronic malabsorption of unknown origin and agammaglobulinemia. During remissions enzyme activities recovered together with mucosal improvement. Low levels of enzyme activities were also seen in some cases of protracted diarrhoea of infancy and chronic malabsorption of unknown origin although only mild mucosal lesions were demonstrated.", "contents": "[Intestinal disaccharidase and alkaline phosphatase activities of jejunal biopsies in small bowel diseases of children (author's transl)]. Intestinal disaccharidase activities were determined in 294 jejunal biopsies obtained from 254 children with various disorders of the small bowel, and alkaline phosphatase activity was measured in 251 biopsies. In normal mucosa a broad range of enzyme activity was found corresponding with the data in the literature. A primary disaccharidase deficiency was observed in 5 children with congenital sucrase-isomaltase deficiency and in a 12-year-old Egyptian boy with acquired lactase deficiency. A secondary generalized depression of disaccharidase activity and a diminution of alkaline phosphatase activity existed chiefly in patients who had severe or moderate mucosal damage, also in active coeliac disease and during gluten loading, in protracted diarrhoea of infancy, chronic malabsorption of unknown origin and agammaglobulinemia. During remissions enzyme activities recovered together with mucosal improvement. Low levels of enzyme activities were also seen in some cases of protracted diarrhoea of infancy and chronic malabsorption of unknown origin although only mild mucosal lesions were demonstrated."} {"id": "PMID:1278186", "title": "[Tryptic and chymotryptic activity in the faeces of children of different age groups (author's transl)].", "content": "Measurement of tryptic and chymotryptic activity in the faeces was not disturbed by bacterial proteolytic activity of different bacteria such as proteus, pseudomonas, coli, enterococci, bacteroides. Both activities within a group follow a logarithmic normal distribution. Lower limit of the standard deviation is 51% upper limit 129% for tryptic activity, respectively 60 and 170% for chymotryptic activity. There were no differences in chymotryptic activity between the 10 age groups comprising 157 healthy children, whereas a significant difference could be found for tryptic activity between premature and older children. Daily fluctuations of the enzyme activities are quite high in the same individual, and only reduced in \"bottlefed\" infants with constant nutrition. In prematures and very young infants chymotryptic activity predominates, later tryptic activity. Influence of increased and decreased bowel movements on deviation of the data was tested. There was, however, no real alteration of enzyme activity due to the bowel dysfunction beyond the standard deviation of the control groups. But passage time and nutrition have to be considered beside other factors in the wide distribution of the enzyme activities and the latter limits the value of this method.", "contents": "[Tryptic and chymotryptic activity in the faeces of children of different age groups (author's transl)]. Measurement of tryptic and chymotryptic activity in the faeces was not disturbed by bacterial proteolytic activity of different bacteria such as proteus, pseudomonas, coli, enterococci, bacteroides. Both activities within a group follow a logarithmic normal distribution. Lower limit of the standard deviation is 51% upper limit 129% for tryptic activity, respectively 60 and 170% for chymotryptic activity. There were no differences in chymotryptic activity between the 10 age groups comprising 157 healthy children, whereas a significant difference could be found for tryptic activity between premature and older children. Daily fluctuations of the enzyme activities are quite high in the same individual, and only reduced in \"bottlefed\" infants with constant nutrition. In prematures and very young infants chymotryptic activity predominates, later tryptic activity. Influence of increased and decreased bowel movements on deviation of the data was tested. There was, however, no real alteration of enzyme activity due to the bowel dysfunction beyond the standard deviation of the control groups. But passage time and nutrition have to be considered beside other factors in the wide distribution of the enzyme activities and the latter limits the value of this method."} {"id": "PMID:1278187", "title": "[Leucine sensitive hypoglycemia. Follow-up studies under treatment with diazoxide (author's transl)].", "content": "Since 1969 leucine sensitive hypoglycemia has been diagnosed in 4 infants. Elevated serum insulin levels suggested hyperinsulinism; in 1 infant islet cell hyperplasia was demonstrated by morphological examination of pancreatic tissue. All cases were treated with diazoxide and have been followed under therapy for periods ranging from 4 months to 6 1/4 years. The upper limit of dosage was 15 mg/kg. The blood glucose values promptly became normal in 2 infants under this regimen. The development of these patients was normal. In the 2 other infants treatment was effective only after the additional restriction of daily protein intake to 2-2.5 g/kg. Severe cerebral damage occurred in one of these infants due to recurrent episodes of hypoglycemia, causing further development to be considerably restricted; the other one developed satisfactorily but with moderate mental retardation. Both children are suffering from cerebral convulsions. In all patients hypertrichosis was the only side effect.", "contents": "[Leucine sensitive hypoglycemia. Follow-up studies under treatment with diazoxide (author's transl)]. Since 1969 leucine sensitive hypoglycemia has been diagnosed in 4 infants. Elevated serum insulin levels suggested hyperinsulinism; in 1 infant islet cell hyperplasia was demonstrated by morphological examination of pancreatic tissue. All cases were treated with diazoxide and have been followed under therapy for periods ranging from 4 months to 6 1/4 years. The upper limit of dosage was 15 mg/kg. The blood glucose values promptly became normal in 2 infants under this regimen. The development of these patients was normal. In the 2 other infants treatment was effective only after the additional restriction of daily protein intake to 2-2.5 g/kg. Severe cerebral damage occurred in one of these infants due to recurrent episodes of hypoglycemia, causing further development to be considerably restricted; the other one developed satisfactorily but with moderate mental retardation. Both children are suffering from cerebral convulsions. In all patients hypertrichosis was the only side effect."} {"id": "PMID:1278188", "title": "[HGH secretion after oral application of L-dopa and L-carbidopa (author's transl)].", "content": "The stimulatory effect of L-Dopa and L-Carbidopa (Nacom) on HGH secretion was determined in 12 children of normal height aged from 6 to 14 years. Each child received a standard dose of 250 mg L-Dopa and 25 mg L-Carbidopa p.o. HGH concentration in the serum was determined at standard intervals. All subjects showed a sufficient increase of HGH. The mean value was 19.6 ng/ml. According to the maximum values of the HGH concentration the sample can be divided into two groups; the first group reached the highest values after 20--40 min, the second one after 60--90 min. On evaluation of the curve of the mean values it appears that 2 blood samples taken 40 and 90 min after the ingestion of L-Dopa and L-Carbidopa are sufficient in order to exclude HGH deficiency. The theoretical background for HGH secretion after stimulation by L-Dopa and L-Carbidopa is discussed.", "contents": "[HGH secretion after oral application of L-dopa and L-carbidopa (author's transl)]. The stimulatory effect of L-Dopa and L-Carbidopa (Nacom) on HGH secretion was determined in 12 children of normal height aged from 6 to 14 years. Each child received a standard dose of 250 mg L-Dopa and 25 mg L-Carbidopa p.o. HGH concentration in the serum was determined at standard intervals. All subjects showed a sufficient increase of HGH. The mean value was 19.6 ng/ml. According to the maximum values of the HGH concentration the sample can be divided into two groups; the first group reached the highest values after 20--40 min, the second one after 60--90 min. On evaluation of the curve of the mean values it appears that 2 blood samples taken 40 and 90 min after the ingestion of L-Dopa and L-Carbidopa are sufficient in order to exclude HGH deficiency. The theoretical background for HGH secretion after stimulation by L-Dopa and L-Carbidopa is discussed."} {"id": "PMID:1278189", "title": "Insulin antibodies in 104 children with diabetes mellitus.", "content": "Binding capacity for porcine, bovine, and human insulin was estimated in 104 diabetic children using homologous systems of iodinated and noniodinated insulin. All patient sera bound porcine and bovine insulin whilst 11.5% did not bind human insulin. There was no clear correlation between duration of insulin treatment and binding capacity. However, some patients with only short duration of treatment had high capacity for porcine insulin. The binding capacity for human insulin was low in most patients. High insulin requirement was on average combined with high binding for bovine insulin. Cases of diabetes, which are difficult to control, treated with individual mixtures of porcine and bovine insulin, often showed high binding for porcine and also for human insuline. The value of estimations of insulin-binding capacity in diabetic children is debatable. However, the high incidence of antibodies seems to justify the use of low immunogenic (monocomponent) insulin preparations.", "contents": "Insulin antibodies in 104 children with diabetes mellitus. Binding capacity for porcine, bovine, and human insulin was estimated in 104 diabetic children using homologous systems of iodinated and noniodinated insulin. All patient sera bound porcine and bovine insulin whilst 11.5% did not bind human insulin. There was no clear correlation between duration of insulin treatment and binding capacity. However, some patients with only short duration of treatment had high capacity for porcine insulin. The binding capacity for human insulin was low in most patients. High insulin requirement was on average combined with high binding for bovine insulin. Cases of diabetes, which are difficult to control, treated with individual mixtures of porcine and bovine insulin, often showed high binding for porcine and also for human insuline. The value of estimations of insulin-binding capacity in diabetic children is debatable. However, the high incidence of antibodies seems to justify the use of low immunogenic (monocomponent) insulin preparations."} {"id": "PMID:1278190", "title": "[On the validity of W170 as a measure of physical performance capacity in the assessment of children with heart disease (author's transl)].", "content": "W170, i.e., the work rate at a heart frequency of 170 beats per minute, and maximal oxygen uptake were determined in one performance in 20 boys and 23 girls from 6 to 16 years of age on a bicycle ergometer. The results were related to normal values according to age and height. In different age and sex groups correlation coefficients between W170 and maximal oxygen uptake amounted to values between 0.36 and 0.66. Accordingly only 13--44% of the variance of maximal oxygen uptake were covered by W170. The imperfect conformity between indirectly and directly measured cardiovascular performance capacity was due to the considerable variability of the maximal heart rate. Accordingly we found correlation coefficients from 0.28 to 0.69 for the relations between maximal heart rate on the one hand and the difference between percentage values of maximal oxygen uptake and W170 on the other hand. That means that the error of an indirect determination by means of the W170 is mostly higher, the more the maximal heart rate differs from the mean value of the group. The estimation of cardiovascular performance capacity by means of the W170 yielded higher relative values than by means of maximal oxygen uptake. The reason for this is probably that in our present investigations we used another type of ergometer than that we had used earlier for determination of normal values of W170, to which we referred in our present investigations. We suggest that the different gyrating mass of different types of ergometers in spite of identical calibration may influence the results via a different mechanical efficiency.", "contents": "[On the validity of W170 as a measure of physical performance capacity in the assessment of children with heart disease (author's transl)]. W170, i.e., the work rate at a heart frequency of 170 beats per minute, and maximal oxygen uptake were determined in one performance in 20 boys and 23 girls from 6 to 16 years of age on a bicycle ergometer. The results were related to normal values according to age and height. In different age and sex groups correlation coefficients between W170 and maximal oxygen uptake amounted to values between 0.36 and 0.66. Accordingly only 13--44% of the variance of maximal oxygen uptake were covered by W170. The imperfect conformity between indirectly and directly measured cardiovascular performance capacity was due to the considerable variability of the maximal heart rate. Accordingly we found correlation coefficients from 0.28 to 0.69 for the relations between maximal heart rate on the one hand and the difference between percentage values of maximal oxygen uptake and W170 on the other hand. That means that the error of an indirect determination by means of the W170 is mostly higher, the more the maximal heart rate differs from the mean value of the group. The estimation of cardiovascular performance capacity by means of the W170 yielded higher relative values than by means of maximal oxygen uptake. The reason for this is probably that in our present investigations we used another type of ergometer than that we had used earlier for determination of normal values of W170, to which we referred in our present investigations. We suggest that the different gyrating mass of different types of ergometers in spite of identical calibration may influence the results via a different mechanical efficiency."} {"id": "PMID:1278191", "title": "Increased intracranial pressure in so-called 'normal-pressure hydrocephalus'.", "content": "Five patients exhibited an apparently communicating hydrocephalus -- type of disorder, with ventricular reflux on the cisternograms, lack of air-encephalographic parasagittal air-filling and clearly enlarged temporal horns. The group seemed heterogeneous, with regard to age distribution; possible etiological factors and duration of the hydrocephalic process. In all 5 patients increased intracranial/intrathecal pressure was observed: in 2 patients, only with intrathecal measurement in the lumbar area, but in the remaining 3 patients with epidural/ventricular fluid pressure monitoring. Continuously increased pressure extending over 1 or more days was observed in these patients. This pressure increase may seem different from the episodic pressure increase previously reported in normal-pressure hydrocephalus. These patients seem to be cases of so-called normal-pressure hydrocephalus according to the commonly accepted criteria. It is therefore suggested that the term normal-pressure hydrocephalus should be abandoned, and replaced by, e.g., low-pressure hydrocephalus, malresorptive or malabsorptive hydrocephalus.", "contents": "Increased intracranial pressure in so-called 'normal-pressure hydrocephalus'. Five patients exhibited an apparently communicating hydrocephalus -- type of disorder, with ventricular reflux on the cisternograms, lack of air-encephalographic parasagittal air-filling and clearly enlarged temporal horns. The group seemed heterogeneous, with regard to age distribution; possible etiological factors and duration of the hydrocephalic process. In all 5 patients increased intracranial/intrathecal pressure was observed: in 2 patients, only with intrathecal measurement in the lumbar area, but in the remaining 3 patients with epidural/ventricular fluid pressure monitoring. Continuously increased pressure extending over 1 or more days was observed in these patients. This pressure increase may seem different from the episodic pressure increase previously reported in normal-pressure hydrocephalus. These patients seem to be cases of so-called normal-pressure hydrocephalus according to the commonly accepted criteria. It is therefore suggested that the term normal-pressure hydrocephalus should be abandoned, and replaced by, e.g., low-pressure hydrocephalus, malresorptive or malabsorptive hydrocephalus."} {"id": "PMID:1278192", "title": "Brain tumors simulating purulent meningitis.", "content": "Three cases of primary brain tumors simulating purulent meningitis have been described. Two patients were infants suffering from ependymoma of the posterior fossa, while the third was a 35-year-old man with astrocytoma of the temporal lobe. All cases were characterized by acute onset with fever, signs of meningeal irritation without any other neurological signs, and marked CSF pleocytosis. The diagnosis in 2 cases was made only at necropsy, and the third case was correctly diagnosed only after a delay. The possible occurrence of brain tumor and meningitis simultaneously was considered and seemed unlikely in our cases. A possible explanation for the clinical and CSF findings was irritation of the leptomeninges by the tumor and its breakdown products.", "contents": "Brain tumors simulating purulent meningitis. Three cases of primary brain tumors simulating purulent meningitis have been described. Two patients were infants suffering from ependymoma of the posterior fossa, while the third was a 35-year-old man with astrocytoma of the temporal lobe. All cases were characterized by acute onset with fever, signs of meningeal irritation without any other neurological signs, and marked CSF pleocytosis. The diagnosis in 2 cases was made only at necropsy, and the third case was correctly diagnosed only after a delay. The possible occurrence of brain tumor and meningitis simultaneously was considered and seemed unlikely in our cases. A possible explanation for the clinical and CSF findings was irritation of the leptomeninges by the tumor and its breakdown products."} {"id": "PMID:1278193", "title": "Progressive multifocal leucoencephalopathy and Rosenthal fibres.", "content": "The present paper is the study of a case of progressive multifocal leucoencephalopathy that appeared in the course of a malignant reticulosis accompanied by paraproteinosis. Due to the lesions in the brain stem and cerebellum, the case evolved clinically as a pure cerebellar form. The particularity of the morphologic aspect, not as yet described, was the abundant presence of Rosenthal fibres in the older demyelination foci. These fibres exhibited a typical structure both in the electron and optic microscope. Emphasis is laid on the connection between the formation of Rosenthal fibres and blastic cellular transformation of the glial system.", "contents": "Progressive multifocal leucoencephalopathy and Rosenthal fibres. The present paper is the study of a case of progressive multifocal leucoencephalopathy that appeared in the course of a malignant reticulosis accompanied by paraproteinosis. Due to the lesions in the brain stem and cerebellum, the case evolved clinically as a pure cerebellar form. The particularity of the morphologic aspect, not as yet described, was the abundant presence of Rosenthal fibres in the older demyelination foci. These fibres exhibited a typical structure both in the electron and optic microscope. Emphasis is laid on the connection between the formation of Rosenthal fibres and blastic cellular transformation of the glial system."} {"id": "PMID:1278194", "title": "Absence of relationships between L-dopa plasma levels and therapeutic effect in Parkinson's disease treated with L-dopa.", "content": "The plasma concentration of dopa was studied in 15 parkinsonian patients after a single administration of L-dopa. The study was undertaken in order to determine if correlation between plasma dopa concentration and clinical performance as a result of the tests carried out before and after a single dose of dopa, was present. Our data confirm the absolute absence of correlation between dopa levels in plasma and clinical improvement during long-term treatment. Moreover, clinical responses to the performance tests were not related to the concentration of circulating L-dopa in the plasma. Therefore dopa levels cannot be useful in clinical practice but only for the prevention of too high concentrations of plasma L-dopa which often cause a few side-effects.", "contents": "Absence of relationships between L-dopa plasma levels and therapeutic effect in Parkinson's disease treated with L-dopa. The plasma concentration of dopa was studied in 15 parkinsonian patients after a single administration of L-dopa. The study was undertaken in order to determine if correlation between plasma dopa concentration and clinical performance as a result of the tests carried out before and after a single dose of dopa, was present. Our data confirm the absolute absence of correlation between dopa levels in plasma and clinical improvement during long-term treatment. Moreover, clinical responses to the performance tests were not related to the concentration of circulating L-dopa in the plasma. Therefore dopa levels cannot be useful in clinical practice but only for the prevention of too high concentrations of plasma L-dopa which often cause a few side-effects."} {"id": "PMID:1278195", "title": "Effects of long-term L-dopa therapy on carbohydrate metabolism in patients with Parkinson's disease.", "content": "Carbohydrate metabolism and insulin secretion were investigated in 26 patients with Parkinson's disease before and during L-dopa treatment. Oral glucose tolerance tests were performed on 13 patients treated with L-dopa alone and on 7 patients treated with L-dopa combined with Carbidopa. Intravenous glucose tolerance tests were performed on additional 6 patients treated with L-dopa alone. Results indicate that chronic L-dopa administration does not modify glucose metabolism. It was observed only a significant decrease of insulin secretion after oral glucose in the early phase (15th day) of treatment with L-dopa alone. This temporary effect may be related to the peripheral conversion of L-dopa to dopamine since insulin secretion during combined therapy was normal. The mechanism by which L-dopa transiently inhibits insulin release is not clear. Perhaps the oral administration of L-dopa alone causes an alteration in some gastrointestinal functions which are involved in the handling of oral glucose.", "contents": "Effects of long-term L-dopa therapy on carbohydrate metabolism in patients with Parkinson's disease. Carbohydrate metabolism and insulin secretion were investigated in 26 patients with Parkinson's disease before and during L-dopa treatment. Oral glucose tolerance tests were performed on 13 patients treated with L-dopa alone and on 7 patients treated with L-dopa combined with Carbidopa. Intravenous glucose tolerance tests were performed on additional 6 patients treated with L-dopa alone. Results indicate that chronic L-dopa administration does not modify glucose metabolism. It was observed only a significant decrease of insulin secretion after oral glucose in the early phase (15th day) of treatment with L-dopa alone. This temporary effect may be related to the peripheral conversion of L-dopa to dopamine since insulin secretion during combined therapy was normal. The mechanism by which L-dopa transiently inhibits insulin release is not clear. Perhaps the oral administration of L-dopa alone causes an alteration in some gastrointestinal functions which are involved in the handling of oral glucose."} {"id": "PMID:1278204", "title": "Sarcoidosis with incomplete bilateral bundle branch block pattern disappearing following steroid therapy: an electrophysiological study.", "content": "A man with a 30-year history of pulmonary sarcoidosis, confirmed by lymph node biopsy and a positive Kveim reaction, developed an incomplete bilateral bundle branch block pattern. Cardiac catherization and angiography revealed normal pressures, hemodynamic parameters and left ventricular contractile pattern; the coronary arteries were patent. His bundle electrograms demonstrated a normal H-V interval that was not altered by atrial pacing. After four weeks of steroid therapy the electrocardiographic abnormality disappeared. However, when restudied at this time, incomplete bilateral bundle branch block pattern could be elicited on atrial pacing and with the extrastimulus technique. Other electrophysiological observations suggested the presence of an AV nodal bypass tract and demonstrated changing intraventricular conduction patterns. The implications of these findings are discussed.", "contents": "Sarcoidosis with incomplete bilateral bundle branch block pattern disappearing following steroid therapy: an electrophysiological study. A man with a 30-year history of pulmonary sarcoidosis, confirmed by lymph node biopsy and a positive Kveim reaction, developed an incomplete bilateral bundle branch block pattern. Cardiac catherization and angiography revealed normal pressures, hemodynamic parameters and left ventricular contractile pattern; the coronary arteries were patent. His bundle electrograms demonstrated a normal H-V interval that was not altered by atrial pacing. After four weeks of steroid therapy the electrocardiographic abnormality disappeared. However, when restudied at this time, incomplete bilateral bundle branch block pattern could be elicited on atrial pacing and with the extrastimulus technique. Other electrophysiological observations suggested the presence of an AV nodal bypass tract and demonstrated changing intraventricular conduction patterns. The implications of these findings are discussed."} {"id": "PMID:1278205", "title": "Sequential hemodynamic studies following mitral fascia lata valve replacement.", "content": "Sequential hemodynamic studies were performed at mean intervals of 6 and 38 months following mitral valve replacement in 10 patients who had angiographically competent fascia lata valves and in whom preoperative hemodynamic studies were available. The cardiac index did not change significantly during postoperative studies as compared with the preoperative values, and its response in relation to oxygen uptake during exercise remained impaired. The mean pulmonary wedge and pulmonary artery pressures showed significant reduction at the first and the second postoperative studies, both at rest and during exercise. Progressive reduction in the pulmonary vascular resistance occurred in patients with high initial values, although the group mean did not alter significantly. The mean diastolic gradient across the mitral fascial valves averaged 8.1 +/- 1.3 mm Hg at rest rising to 22.5 +/- 2.4 mm Hg during exercise (P less than 0.001), and the calculated mitral valve area was 1.9 +/- 0.22 cm2 at rest and 2.36 +/- 0.3 cm2 during exercise (P less than 0.02). This study indicates that the insertion of stented mitral fascia lata valves results in significant hemodynamic improvement, which is maintained at least for 3 years after surgery, in patients with competent valves. However, a degree of obstruction to the forward flow is apparent especially during exercise, despite the central flow design of the valve.", "contents": "Sequential hemodynamic studies following mitral fascia lata valve replacement. Sequential hemodynamic studies were performed at mean intervals of 6 and 38 months following mitral valve replacement in 10 patients who had angiographically competent fascia lata valves and in whom preoperative hemodynamic studies were available. The cardiac index did not change significantly during postoperative studies as compared with the preoperative values, and its response in relation to oxygen uptake during exercise remained impaired. The mean pulmonary wedge and pulmonary artery pressures showed significant reduction at the first and the second postoperative studies, both at rest and during exercise. Progressive reduction in the pulmonary vascular resistance occurred in patients with high initial values, although the group mean did not alter significantly. The mean diastolic gradient across the mitral fascial valves averaged 8.1 +/- 1.3 mm Hg at rest rising to 22.5 +/- 2.4 mm Hg during exercise (P less than 0.001), and the calculated mitral valve area was 1.9 +/- 0.22 cm2 at rest and 2.36 +/- 0.3 cm2 during exercise (P less than 0.02). This study indicates that the insertion of stented mitral fascia lata valves results in significant hemodynamic improvement, which is maintained at least for 3 years after surgery, in patients with competent valves. However, a degree of obstruction to the forward flow is apparent especially during exercise, despite the central flow design of the valve."} {"id": "PMID:1278206", "title": "Hemodynamic effects of lidoflazine during graded levels of bicycle exercise in normal subjects.", "content": "The hemodynamic effects of lidoflazine were studied in 12 young healthy subjects who received the drug orally (240 mg daily) for 8 weeks. During exercise after lidoflazine, heart rate (-2.6%), mean arterial pressure (-3.1%), arterio-venous oxygen (A-V02) difference (-3.4%), pressure rate product (-6.2%), and systemic vascular resistance (-8.6%) were significantly lower, while cardiac output (+5.4%) and stroke volume (+8.3%) were significantly greater. The maximal heart rate was lower after lidoflazine (-6 beats/min) but the maximal oxygen intake (VO2max) was not affected by the drug. The major hemodynamic effects of lidoflazine appear to be, on the one hand, an unexplained decrease in heart rate, and on the other, a decrease in systemic vascular resistance; the latter, which was expected from a vasodilator, could account for the greater stroke volume and contributes to the decrease of the pressure rate product. Lidoflazine has another unexplained effect, i.e. a decrease of the A-VO2 difference, suggesting a decreased peripheral extraction of oxygen at rest as well as during submaximal and maximal exercise.", "contents": "Hemodynamic effects of lidoflazine during graded levels of bicycle exercise in normal subjects. The hemodynamic effects of lidoflazine were studied in 12 young healthy subjects who received the drug orally (240 mg daily) for 8 weeks. During exercise after lidoflazine, heart rate (-2.6%), mean arterial pressure (-3.1%), arterio-venous oxygen (A-V02) difference (-3.4%), pressure rate product (-6.2%), and systemic vascular resistance (-8.6%) were significantly lower, while cardiac output (+5.4%) and stroke volume (+8.3%) were significantly greater. The maximal heart rate was lower after lidoflazine (-6 beats/min) but the maximal oxygen intake (VO2max) was not affected by the drug. The major hemodynamic effects of lidoflazine appear to be, on the one hand, an unexplained decrease in heart rate, and on the other, a decrease in systemic vascular resistance; the latter, which was expected from a vasodilator, could account for the greater stroke volume and contributes to the decrease of the pressure rate product. Lidoflazine has another unexplained effect, i.e. a decrease of the A-VO2 difference, suggesting a decreased peripheral extraction of oxygen at rest as well as during submaximal and maximal exercise."} {"id": "PMID:1278207", "title": "Assessment of immediate prognosis in acute myocardial infarction by a new noninvasive hemodynamic index.", "content": "A prognostic index for acute myocardial infarction was developed from noninvasively accessible parameters, gathered prospectively within 24 h from the onset of symptoms in 185 consecutive patients. Of the 35 patients who died in hospital, 30 had power failure. The items subjected to discriminant function analysis were: sex, age, number of previous infarctions, present infarction transor nontransmural, heart rate, systolic arterial pressure (SAP), left ventricular ejection time (LVET), cardiothoracic ratio, and grade of pulmonary venous congestion scored 0-3 (PVC0-3). The items possessing the best predictive power were, in the order of their strength: age, SAP, LVET and PVCO-3; i.e., hemodynamically, afterload, stroke volume and preload. The discriminant function (DF) giving the prognostic score was: DF=3.9Xage(yr)-1.3X SAP (mm Hg) - 1.4 X LVET (msec) + 25.3 X PVC0-3 + 775.3 Score 550 was exceeded by 87% of the patients dying of power failure and only 16% of the survivors, and it was less in 84% of the survivors and 13% of those dying. To test the validity of the index it was applied to another series consisting of 100 consecutive patients and very similar results were obtained, suggesting that the index is of practical value in predicting hemodynamic deterioration early and by simple noninvasive means.", "contents": "Assessment of immediate prognosis in acute myocardial infarction by a new noninvasive hemodynamic index. A prognostic index for acute myocardial infarction was developed from noninvasively accessible parameters, gathered prospectively within 24 h from the onset of symptoms in 185 consecutive patients. Of the 35 patients who died in hospital, 30 had power failure. The items subjected to discriminant function analysis were: sex, age, number of previous infarctions, present infarction transor nontransmural, heart rate, systolic arterial pressure (SAP), left ventricular ejection time (LVET), cardiothoracic ratio, and grade of pulmonary venous congestion scored 0-3 (PVC0-3). The items possessing the best predictive power were, in the order of their strength: age, SAP, LVET and PVCO-3; i.e., hemodynamically, afterload, stroke volume and preload. The discriminant function (DF) giving the prognostic score was: DF=3.9Xage(yr)-1.3X SAP (mm Hg) - 1.4 X LVET (msec) + 25.3 X PVC0-3 + 775.3 Score 550 was exceeded by 87% of the patients dying of power failure and only 16% of the survivors, and it was less in 84% of the survivors and 13% of those dying. To test the validity of the index it was applied to another series consisting of 100 consecutive patients and very similar results were obtained, suggesting that the index is of practical value in predicting hemodynamic deterioration early and by simple noninvasive means."} {"id": "PMID:1278208", "title": "Transcutaneous aortovelography: reproducibility in adults and children.", "content": "Transcutaneous aortovelography (TAV), a new ultrasonic technique for measuring instantaneous mainstream blood velocity in the aorta, is described. The technique uses the Doppler shift principle. The highest local blood velocity within the aortic arch can be recorded from a transducer placed in the suprasternal notch. Inspection of the systolic complexes recorded allows measurement of peak velocity, systolic complex area (proportional to ejected stroke volume), mean (time averaged) blood velocity and initial systolic acceleration. Formal analysis of variance was performed on measurements made by the five observers on 11 healthy adults and by 2 observers on 10 healthy children. Coefficients of variation of from 4 to 8% were found of all variables other than acceleration where the variation was up to 16%. Peak velocities in adults ranged from 97 to 130 cm/sec and were higher in children.", "contents": "Transcutaneous aortovelography: reproducibility in adults and children. Transcutaneous aortovelography (TAV), a new ultrasonic technique for measuring instantaneous mainstream blood velocity in the aorta, is described. The technique uses the Doppler shift principle. The highest local blood velocity within the aortic arch can be recorded from a transducer placed in the suprasternal notch. Inspection of the systolic complexes recorded allows measurement of peak velocity, systolic complex area (proportional to ejected stroke volume), mean (time averaged) blood velocity and initial systolic acceleration. Formal analysis of variance was performed on measurements made by the five observers on 11 healthy adults and by 2 observers on 10 healthy children. Coefficients of variation of from 4 to 8% were found of all variables other than acceleration where the variation was up to 16%. Peak velocities in adults ranged from 97 to 130 cm/sec and were higher in children."} {"id": "PMID:1278209", "title": "Radiation pericarditis and myocardial fibrosis.", "content": "The case of a 45-yr-old man with constrictive pericarditis due to radiation for Hodgkin's disease is described. After pericardiectomy and clinical condition did not improve. At necropsy an extensive fibrosis of the myocardium especially located in the anterior part of the heart was found. The clinical consequences of this finding with respect to surgical treatment are briefly discussed.", "contents": "Radiation pericarditis and myocardial fibrosis. The case of a 45-yr-old man with constrictive pericarditis due to radiation for Hodgkin's disease is described. After pericardiectomy and clinical condition did not improve. At necropsy an extensive fibrosis of the myocardium especially located in the anterior part of the heart was found. The clinical consequences of this finding with respect to surgical treatment are briefly discussed."} {"id": "PMID:1278211", "title": "Dependence of calcium release, tension generation and restoring forces on sarcomere length in skinned cardiac cells.", "content": "The ascending limb of the length-tension diagram was studied in single skinned (sarcolemma-free) cardiac cells of rat ventricle. The free (Ca2+) in the perfusing solutions was buffered with ethyleneglycol-bis(beta-aminoethyl)N,N'-tetraacetic acid (EGTA). Tension was recorded with a photo-diode force transducer (detection limit: 1 mug, compliance 2-3 mum/mg) and was expressed as a function of the sarcomere length (SL) measured during contraction with a high-speed movie camera. When the SL was decreased by a brief (1-2 sec) exposure to high free (Ca2+), a restoring force qas observed upon return of the cell to a relaxing solution. The restoring force was comprised of two components: (1) a rapid elongation to 1.57 identical to 0.06 mum developing a negative tension (relaxing force) as large as 4% of the maximum positive tension, which was observed in both skinned cells and in single myofibrils, and (2) a slow elongation from 1.57 identical to 0.06 to 1.93 identical to 0.14 mum, which was observed in skinned cells but not in single myofibrils. When the SL was kept extremely short by continuous Ca2+ activation for more than 30 sec, a shortening of the A band much below 1.0 mum persisted for several minutes after imposed re-elongation of the sarcomers (delta state). The amplitude of the tonic tension developed by direct activation of the myofilaments in the presence of high total (EGTA) was maximum for 2.20 mum SL and decreased very little when the SL was decreased. However, the decrease of tension became more pronounced at SL shorter than 1.55 mum when polyvinylpyrrolidone was added to the solutions at a concentration reducing the swelling of the myofilament lattice. This finding imposes some caution in applying the results obtained in skinned cardiac cells to intact tissue. The SL-tension diagram of the phasic contractions induced by Ca2+-triggered of Ca2+ in the presence of a slight EGTA buffering was similar to the SL-tension diagram of the intact rat ventricular muscle when the latter was expressed as a function of the active SL. In contrast, the SL-tension diagram of caffeine-induced phasic contractions was similar to that of the tonic tension produced by direct activation of the myofilaments. Decreasing SL results therefore in a partial inhibition of the Ca2+ triggered release process. It was concluded that Starling's Law may correspond to a length-dependence of several mechanisms including Ca2+-triggered release from the SR, interaction between thick and thin filaments and restoring forces.", "contents": "Dependence of calcium release, tension generation and restoring forces on sarcomere length in skinned cardiac cells. The ascending limb of the length-tension diagram was studied in single skinned (sarcolemma-free) cardiac cells of rat ventricle. The free (Ca2+) in the perfusing solutions was buffered with ethyleneglycol-bis(beta-aminoethyl)N,N'-tetraacetic acid (EGTA). Tension was recorded with a photo-diode force transducer (detection limit: 1 mug, compliance 2-3 mum/mg) and was expressed as a function of the sarcomere length (SL) measured during contraction with a high-speed movie camera. When the SL was decreased by a brief (1-2 sec) exposure to high free (Ca2+), a restoring force qas observed upon return of the cell to a relaxing solution. The restoring force was comprised of two components: (1) a rapid elongation to 1.57 identical to 0.06 mum developing a negative tension (relaxing force) as large as 4% of the maximum positive tension, which was observed in both skinned cells and in single myofibrils, and (2) a slow elongation from 1.57 identical to 0.06 to 1.93 identical to 0.14 mum, which was observed in skinned cells but not in single myofibrils. When the SL was kept extremely short by continuous Ca2+ activation for more than 30 sec, a shortening of the A band much below 1.0 mum persisted for several minutes after imposed re-elongation of the sarcomers (delta state). The amplitude of the tonic tension developed by direct activation of the myofilaments in the presence of high total (EGTA) was maximum for 2.20 mum SL and decreased very little when the SL was decreased. However, the decrease of tension became more pronounced at SL shorter than 1.55 mum when polyvinylpyrrolidone was added to the solutions at a concentration reducing the swelling of the myofilament lattice. This finding imposes some caution in applying the results obtained in skinned cardiac cells to intact tissue. The SL-tension diagram of the phasic contractions induced by Ca2+-triggered of Ca2+ in the presence of a slight EGTA buffering was similar to the SL-tension diagram of the intact rat ventricular muscle when the latter was expressed as a function of the active SL. In contrast, the SL-tension diagram of caffeine-induced phasic contractions was similar to that of the tonic tension produced by direct activation of the myofilaments. Decreasing SL results therefore in a partial inhibition of the Ca2+ triggered release process. It was concluded that Starling's Law may correspond to a length-dependence of several mechanisms including Ca2+-triggered release from the SR, interaction between thick and thin filaments and restoring forces."} {"id": "PMID:1278212", "title": "Postextrasystolic potentiation in man.", "content": "Postextrasystolic potentiation (PESP) is a pre- and afterload-independent property of the myocardium. Therefore it has been used to study left ventricular (LV) contractile state in patients with coronary heart disease and normals. Using a computer-controlled cardiac stimulator, regular rhythms with just above sinus frequency were applied to the right atrium and interrupted after every 20th beat by one shorter interval after varying delays. The next stimulus interval was corrected in such a way that the resulting R-R interval was the same as the basic R-R interval. Control of the postextrasystolic R-R interval is a prerequisite for meaningful and quantitative evaluation of PESP. Of 166 basic and postextrasystolic beats in 12 patients LV pressures (P), obtained with a catheter tipmanometer, were analyzed. There was no significant difference in enddiastolic P between pre- and postextrasystolic beats. Peak dP/dt, time to peak dP/dt, (dP/dt)/P at a left ventricular P of 50 mm Hg and Vmax were used as indices of left ventricular contractile state. It was found that on increasing prematurity of the extrasystolic beat, there was a progressive and reproducible increase of these indices (selfevidently a decrease in the case of the time to reach peak dP/dt). Using Vmax as an index of contractile state, no significant PESP could be demonstrated in the two patients with very enlarged left ventricular volumes and depressed ejection fractions. PESP, elicted in this (only allowable) way, is an integral, quantitative and reproducible method for LV contractility estimation in man.", "contents": "Postextrasystolic potentiation in man. Postextrasystolic potentiation (PESP) is a pre- and afterload-independent property of the myocardium. Therefore it has been used to study left ventricular (LV) contractile state in patients with coronary heart disease and normals. Using a computer-controlled cardiac stimulator, regular rhythms with just above sinus frequency were applied to the right atrium and interrupted after every 20th beat by one shorter interval after varying delays. The next stimulus interval was corrected in such a way that the resulting R-R interval was the same as the basic R-R interval. Control of the postextrasystolic R-R interval is a prerequisite for meaningful and quantitative evaluation of PESP. Of 166 basic and postextrasystolic beats in 12 patients LV pressures (P), obtained with a catheter tipmanometer, were analyzed. There was no significant difference in enddiastolic P between pre- and postextrasystolic beats. Peak dP/dt, time to peak dP/dt, (dP/dt)/P at a left ventricular P of 50 mm Hg and Vmax were used as indices of left ventricular contractile state. It was found that on increasing prematurity of the extrasystolic beat, there was a progressive and reproducible increase of these indices (selfevidently a decrease in the case of the time to reach peak dP/dt). Using Vmax as an index of contractile state, no significant PESP could be demonstrated in the two patients with very enlarged left ventricular volumes and depressed ejection fractions. PESP, elicted in this (only allowable) way, is an integral, quantitative and reproducible method for LV contractility estimation in man."} {"id": "PMID:1278213", "title": "Calibrated apexcardiography and assessment of left ventricular dynamics in man.", "content": "Using a calibrated displacement transducer, the total amplitude of the systolic wave of the left apexcardiogram (S), its first derivative (dS) and the normalized first derivative (nS), were evaluated as noninvasive indices of left ventricular function in human subjects. A strong correlation was present between peak dS and S in normal subjects (r=0.95, P less than 0.001). At an identical S, abnormal hearts had a lower peak dS, and this allowed a separation between groups with normal and abnormal ventricular dynamics. The index peak nS was significantly lower in patients with congestive cardiomyopathy (P less than 0.005) and ischemica heart disease in the presence of a low ejection fraction (P less than 0.001). It correlated significantly with LVEDP (r=-0.69, P less than 0.001), with ejection fraction (r=0.66, P less than 0.001) and with left ventricular contractility indices derived from isovolumic left ventricular pressure and its first derivative, recorded simultaneously by means of high fidelity micromanometers (peak VCE: r=0.76; Vmax total pressure: r=0.70; peak dP/dt: r = 0.69; P less than 0.001). The index peak nS was superior to S and peak dS, being less variable, independent of thorax circumference and better correlated with hemodynamic parameters. A close relationship was also present between the total amplitude of the atrial wave (A) and its peak first derivative (peak dA) in normal subjects (r = 0.98, P less than 0.001). For an identical A wave amplitude, patients with an increased left ventricular anddiastolic volume had lower values for peak dA (P less than 0.001).", "contents": "Calibrated apexcardiography and assessment of left ventricular dynamics in man. Using a calibrated displacement transducer, the total amplitude of the systolic wave of the left apexcardiogram (S), its first derivative (dS) and the normalized first derivative (nS), were evaluated as noninvasive indices of left ventricular function in human subjects. A strong correlation was present between peak dS and S in normal subjects (r=0.95, P less than 0.001). At an identical S, abnormal hearts had a lower peak dS, and this allowed a separation between groups with normal and abnormal ventricular dynamics. The index peak nS was significantly lower in patients with congestive cardiomyopathy (P less than 0.005) and ischemica heart disease in the presence of a low ejection fraction (P less than 0.001). It correlated significantly with LVEDP (r=-0.69, P less than 0.001), with ejection fraction (r=0.66, P less than 0.001) and with left ventricular contractility indices derived from isovolumic left ventricular pressure and its first derivative, recorded simultaneously by means of high fidelity micromanometers (peak VCE: r=0.76; Vmax total pressure: r=0.70; peak dP/dt: r = 0.69; P less than 0.001). The index peak nS was superior to S and peak dS, being less variable, independent of thorax circumference and better correlated with hemodynamic parameters. A close relationship was also present between the total amplitude of the atrial wave (A) and its peak first derivative (peak dA) in normal subjects (r = 0.98, P less than 0.001). For an identical A wave amplitude, patients with an increased left ventricular anddiastolic volume had lower values for peak dA (P less than 0.001)."} {"id": "PMID:1278214", "title": "The analysis of size, shape and contraction pattern of the right ventricle from angiocardiograms.", "content": "This paper describes an approach to assess quantitatively videoangiocardiograms of the geometrically complex right ventricle with the aid of an automated roentgen-television-computer system. The influence of spatial positions and heart phase on the accuracy of right ventricular volume determination with biplane and single plane area-length and multiple slices methods was defined on the basis of a special cast study. Without considering position and phase a relative deviation - with a biplane procedure - of not equal to 11.9% has to be faced, which will be reduced to not equal to 8.8% when position, and to not equal to 6.2% when in addition the phase of the cardiac cycle is taken into consideration. Fourier analysis was applied to biplane silhouettes and 'true' cross-sections of mechanically sliced human right ventricular casts in order to arrive at 3-D 'norm ventricles' as reference for size and shape analysis of beating normal and diseased hearts. For contraction pattern analysis the dimensional information from each X-ray plane was processed independently. Selected points (anatomical landmarks), being marked with an x/y coder, served as internal reference system. Multiple parallel diameters, their directions given by a pair of indicated points or by a freely selected angle, were followed throughout the cardiac cycle. Applied was the method to angiocardiograms with normal hearts and those with ASD, pulmonic stenoses, and postoperative tetralogies of Fallot. It can be concluded that on the basis of videoangiocardiograms (1) right ventricular volume can be determinded with a defined and acceptable accuracy, with both biplane and single plane procedures, if one takes into consideration the spatial position and the cardiac phase, (2) right ventricular shape can be quantitated for an objective description, and (3) right ventricular contraction and relaxation processes can be assessed and quantitated for normal and diseased right ventricles.", "contents": "The analysis of size, shape and contraction pattern of the right ventricle from angiocardiograms. This paper describes an approach to assess quantitatively videoangiocardiograms of the geometrically complex right ventricle with the aid of an automated roentgen-television-computer system. The influence of spatial positions and heart phase on the accuracy of right ventricular volume determination with biplane and single plane area-length and multiple slices methods was defined on the basis of a special cast study. Without considering position and phase a relative deviation - with a biplane procedure - of not equal to 11.9% has to be faced, which will be reduced to not equal to 8.8% when position, and to not equal to 6.2% when in addition the phase of the cardiac cycle is taken into consideration. Fourier analysis was applied to biplane silhouettes and 'true' cross-sections of mechanically sliced human right ventricular casts in order to arrive at 3-D 'norm ventricles' as reference for size and shape analysis of beating normal and diseased hearts. For contraction pattern analysis the dimensional information from each X-ray plane was processed independently. Selected points (anatomical landmarks), being marked with an x/y coder, served as internal reference system. Multiple parallel diameters, their directions given by a pair of indicated points or by a freely selected angle, were followed throughout the cardiac cycle. Applied was the method to angiocardiograms with normal hearts and those with ASD, pulmonic stenoses, and postoperative tetralogies of Fallot. It can be concluded that on the basis of videoangiocardiograms (1) right ventricular volume can be determinded with a defined and acceptable accuracy, with both biplane and single plane procedures, if one takes into consideration the spatial position and the cardiac phase, (2) right ventricular shape can be quantitated for an objective description, and (3) right ventricular contraction and relaxation processes can be assessed and quantitated for normal and diseased right ventricles."} {"id": "PMID:1278216", "title": "Vertebrate striated muscle: length dependence of calcium release during contraction.", "content": "It is well known that the force-generating ability of vertebrate striated muscle depends upon its length. At lengths longer than the optimum there is a close correlation between decreasing overlap of the myofilaments and the lessening of contractile force, but at lengths shorter than the optimem additional factors may contribute to decreased contracility. For example, the release of calcium into the myofilament space is decreased during contractions at short muscle lengths, and the morphological changes seen in light and electron micrographs of shortening fibers suggest that the decreased calcium release occurs in the core of the fiber. This length dependent change in calcium release may be one of the factors determining the decrease in contractility with shortening.", "contents": "Vertebrate striated muscle: length dependence of calcium release during contraction. It is well known that the force-generating ability of vertebrate striated muscle depends upon its length. At lengths longer than the optimum there is a close correlation between decreasing overlap of the myofilaments and the lessening of contractile force, but at lengths shorter than the optimem additional factors may contribute to decreased contracility. For example, the release of calcium into the myofilament space is decreased during contractions at short muscle lengths, and the morphological changes seen in light and electron micrographs of shortening fibers suggest that the decreased calcium release occurs in the core of the fiber. This length dependent change in calcium release may be one of the factors determining the decrease in contractility with shortening."} {"id": "PMID:1278218", "title": "Length as a factor in excitation-contraction coupling in heart muscle: an investigation of mechanical transients in strontium-mediated contractions.", "content": "Sr-mediated contractions have been used to provide an analogue of the normal twitch contraction but with a plateau phase of steady-state activity. An abrupt change of load during the plateau induced an isotonic oscillatory response whose frequency was generally related to the length at which it occurred but could be independently increased by adrenaline or caffeine. The response was not specific for Sr, being seen also in Sr- or Ca-activated K-contractures. The isotonic oscillatory response was less damped than the corresponding isometric transient, and spontaneous isotonic oscillation often occurred following the initial shortening phase, suggesting that the change in length rather than the change in load was the causal perturbation. In cat but not frog preparations a second slower oscillation, also influenced by adrenaline, could be induced. Analysis of velocity--length relations indicates that the isotonic oscillations observed during the plateau phase are analogous to the velocity transients previously described in twitch contractions, but then only in three states characterized implicitly by a relatively poor capacity for internal sequestration. These findings provide evidence that length influences the level of activation of the contractile proteins during shortening in heart muscle, probably through changing Sr/Ca availability.", "contents": "Length as a factor in excitation-contraction coupling in heart muscle: an investigation of mechanical transients in strontium-mediated contractions. Sr-mediated contractions have been used to provide an analogue of the normal twitch contraction but with a plateau phase of steady-state activity. An abrupt change of load during the plateau induced an isotonic oscillatory response whose frequency was generally related to the length at which it occurred but could be independently increased by adrenaline or caffeine. The response was not specific for Sr, being seen also in Sr- or Ca-activated K-contractures. The isotonic oscillatory response was less damped than the corresponding isometric transient, and spontaneous isotonic oscillation often occurred following the initial shortening phase, suggesting that the change in length rather than the change in load was the causal perturbation. In cat but not frog preparations a second slower oscillation, also influenced by adrenaline, could be induced. Analysis of velocity--length relations indicates that the isotonic oscillations observed during the plateau phase are analogous to the velocity transients previously described in twitch contractions, but then only in three states characterized implicitly by a relatively poor capacity for internal sequestration. These findings provide evidence that length influences the level of activation of the contractile proteins during shortening in heart muscle, probably through changing Sr/Ca availability."} {"id": "PMID:1278219", "title": "Sarcomere dynamics in intact cardiac muscle.", "content": "Elastic properties, length-tension relations, and some characteristics of unloaded shortening were measured at the sarcomere level in rat papillary muscles. Muscle length during contraction was controlled by a servo system, while instantaneous sarcomere length was measured with a light diffraction technique. Muscles quick-released to zero load recoiled by 6% of their length; of this, sarcomere shortening amounted to only 1.6%, the remainder of the series elastic recoil occurring outside the striated region of the muscle, i.e. at the damaged ends of the specimen adjacent to the mounting clips. The length-tension relation was obtained with the sarcomere length maintained constant during contraction. Peak isometric tension increased linearly with sarcomere length from 1.6 to 2.1 mum; but between 2.1 and 2.3 mum tension appeared to be constant. The velocity of sarcomere shortening in an unloaded contraction bore a functional relation to sarcomere length which was similar to that of isometric tension. Both isometric tension and velocity of unloaded shortening reached their peak values relatively early in the contractile cycle.", "contents": "Sarcomere dynamics in intact cardiac muscle. Elastic properties, length-tension relations, and some characteristics of unloaded shortening were measured at the sarcomere level in rat papillary muscles. Muscle length during contraction was controlled by a servo system, while instantaneous sarcomere length was measured with a light diffraction technique. Muscles quick-released to zero load recoiled by 6% of their length; of this, sarcomere shortening amounted to only 1.6%, the remainder of the series elastic recoil occurring outside the striated region of the muscle, i.e. at the damaged ends of the specimen adjacent to the mounting clips. The length-tension relation was obtained with the sarcomere length maintained constant during contraction. Peak isometric tension increased linearly with sarcomere length from 1.6 to 2.1 mum; but between 2.1 and 2.3 mum tension appeared to be constant. The velocity of sarcomere shortening in an unloaded contraction bore a functional relation to sarcomere length which was similar to that of isometric tension. Both isometric tension and velocity of unloaded shortening reached their peak values relatively early in the contractile cycle."} {"id": "PMID:1278220", "title": "Physiological pump loading of isolated cardiac muscle.", "content": "Cat papillary muscles were subjected to a continuously changing load, resulting from an analysis of the left ventricle as a muscle pump system. The papillary muscle was assumed to be part of a circumferential bundle of muscle fibers of a simplified ejecting ventricle. The load included the pressure--stress relationship of this ventricle and the peripheral vascular load with its inertial, resistive and capacitive components. When this loading function was imposed on a shortening muscle through an electronic feedback circuit, the time course of force development and the velocity versus force plots closely resembled data obtained in the intact heart. Analysis of mechanical work (delta 1 X f) and power (V X f) and their respective time course permitted distinction between changes of contractile performance due to (1) positive or negative inotropic interventions, (2) altered hypothetical ventricular dimensions and changed preload, and (3) the long-term load-dependent memory of cardiac muscle.", "contents": "Physiological pump loading of isolated cardiac muscle. Cat papillary muscles were subjected to a continuously changing load, resulting from an analysis of the left ventricle as a muscle pump system. The papillary muscle was assumed to be part of a circumferential bundle of muscle fibers of a simplified ejecting ventricle. The load included the pressure--stress relationship of this ventricle and the peripheral vascular load with its inertial, resistive and capacitive components. When this loading function was imposed on a shortening muscle through an electronic feedback circuit, the time course of force development and the velocity versus force plots closely resembled data obtained in the intact heart. Analysis of mechanical work (delta 1 X f) and power (V X f) and their respective time course permitted distinction between changes of contractile performance due to (1) positive or negative inotropic interventions, (2) altered hypothetical ventricular dimensions and changed preload, and (3) the long-term load-dependent memory of cardiac muscle."} {"id": "PMID:1278221", "title": "Preload, afterload, and the role of afterload mismatch in the descending limb of cardiac function.", "content": "Ventricular function can be analyzed from measures of the ejecting phase of contraction (e.g. velocity and extent of wall shortening) in terms of the appropriateness of the matching between afterload and the level of inotropic state, as modulated by the preload. In the normal heart, under controlled conditions an afterload mismatch can be readily induced if the preload is not allowed to compensate for an increased afterload, or if the limit of the Frank--Starling reserve has been reached. In the conscious animal and in man, measures such as the mean velocity of fiber shortening (VCF, corrected for heart size) are relatively constant in the basal state, and when the normal left ventricle adapts successfully over several weeks to sustained experimental volume or pressure overload, the ejection phase measures remain normal per unit of muscle. However, if the inotropic state is considerably reduced, a mismatch between afterload and contractility (reduced VCF) will be evident in the basal state even when the afterload is normal. Failure to maintain normal ejection indices under conditions of acute or chronic mechanical overload can be explained in terms of an excessive afterload relative to the degree of hypertrophy, the level of inotropic state, and the Frank--Starling rereserve. The concept of afterload mismatch is illustrated by experimental data and used as a basis for characterizing responses to afterload changes in the clinical setting.", "contents": "Preload, afterload, and the role of afterload mismatch in the descending limb of cardiac function. Ventricular function can be analyzed from measures of the ejecting phase of contraction (e.g. velocity and extent of wall shortening) in terms of the appropriateness of the matching between afterload and the level of inotropic state, as modulated by the preload. In the normal heart, under controlled conditions an afterload mismatch can be readily induced if the preload is not allowed to compensate for an increased afterload, or if the limit of the Frank--Starling reserve has been reached. In the conscious animal and in man, measures such as the mean velocity of fiber shortening (VCF, corrected for heart size) are relatively constant in the basal state, and when the normal left ventricle adapts successfully over several weeks to sustained experimental volume or pressure overload, the ejection phase measures remain normal per unit of muscle. However, if the inotropic state is considerably reduced, a mismatch between afterload and contractility (reduced VCF) will be evident in the basal state even when the afterload is normal. Failure to maintain normal ejection indices under conditions of acute or chronic mechanical overload can be explained in terms of an excessive afterload relative to the degree of hypertrophy, the level of inotropic state, and the Frank--Starling rereserve. The concept of afterload mismatch is illustrated by experimental data and used as a basis for characterizing responses to afterload changes in the clinical setting."} {"id": "PMID:1278222", "title": "The physics of left ventricular ejection and its implications for muscle mechanics.", "content": "The ejection stage of the left ventricle of the heart is analyzed using the proper form of Newton's Second Law of Motion and a simple cylindrical ventricular model. The Laplace relation is then used to calculate the dynamic relationship between force, velocity and acceleration in an average, circumferential, equitorial myocardial wall fiber, yielding: Fm=Fa + Cacf + Dvcf2 where Fm is the force in the fiber, Fa the fiber force that would be required to match aortic pressure, acf the acceleration and vcf the velocity of shortening of the fiber. C is a constant, and D is a geometrical parameter that varies smoothly with time. The significance of the above equation is discussed both in terms of muscle function (total muscular force) and pump function afterload Fa and the differential force, Fm - Fa): The afterload component Fa provides the pressure head needed to force the blood through the capillaries (Poiseuille flow) and varies with time in accordance with the impedance of the vascular system (auxotonic loading). The differential component force Fm - Fa provides the ventricular impulse needed to overcome the inertia of the system due to (1) the mass of the blood, (2) the geometrical constriction of the outflow tract as one moves downstream (Bernoulli effect), and (2) the moving ventricular walls. Analysis of this sort should help in attempting to separate the intrinsic properties of cardiac muscle and the pump function of the intact heart. The important role that isolated muscle experiments can play in this effort is discussed.", "contents": "The physics of left ventricular ejection and its implications for muscle mechanics. The ejection stage of the left ventricle of the heart is analyzed using the proper form of Newton's Second Law of Motion and a simple cylindrical ventricular model. The Laplace relation is then used to calculate the dynamic relationship between force, velocity and acceleration in an average, circumferential, equitorial myocardial wall fiber, yielding: Fm=Fa + Cacf + Dvcf2 where Fm is the force in the fiber, Fa the fiber force that would be required to match aortic pressure, acf the acceleration and vcf the velocity of shortening of the fiber. C is a constant, and D is a geometrical parameter that varies smoothly with time. The significance of the above equation is discussed both in terms of muscle function (total muscular force) and pump function afterload Fa and the differential force, Fm - Fa): The afterload component Fa provides the pressure head needed to force the blood through the capillaries (Poiseuille flow) and varies with time in accordance with the impedance of the vascular system (auxotonic loading). The differential component force Fm - Fa provides the ventricular impulse needed to overcome the inertia of the system due to (1) the mass of the blood, (2) the geometrical constriction of the outflow tract as one moves downstream (Bernoulli effect), and (2) the moving ventricular walls. Analysis of this sort should help in attempting to separate the intrinsic properties of cardiac muscle and the pump function of the intact heart. The important role that isolated muscle experiments can play in this effort is discussed."} {"id": "PMID:1278223", "title": "Left ventricle as a compression pump.", "content": "Pressure-volume relationship of the left ventricle at endsystole was studied in three different series of experiment on the dog. Intraventricular pressure was measured with a miniature gauge at the apex. Intraventricular volume was accurately measured by three different methods: (1) plethysmographically with a cardiometer cup, (2) with an intraventricular balloon and a volumetric cylinder, and (3) with the same balloon and areciprocal pump which could clamp the endsystolic volume. We found consistently that as long as the contractile state was stable the endayatolic pressure-volume relationship curve was largely independent of the loading conditions such as enddiastolic volume and ventricular afterload pressure and also of whether the mode of contraction was isovolumic, auxobaric or physiologically ejecting. When the endsystolic pressure was kept unchanged in the ventricle with a stable contractile state, the intraventricular volume decreased to the same volume as given by the endsystolic pressure-volume relationship and the afterload pressure. When the endsystolic volume was maintained constant, the ventricle developed at the end of systole almost the same pressure as that predicted from the same endsystolic pressure-volume relationship. The endsystolic pressure-volume relationship, therefore, uniquely characterizes the degree of ventricular compression under a given contractile state.", "contents": "Left ventricle as a compression pump. Pressure-volume relationship of the left ventricle at endsystole was studied in three different series of experiment on the dog. Intraventricular pressure was measured with a miniature gauge at the apex. Intraventricular volume was accurately measured by three different methods: (1) plethysmographically with a cardiometer cup, (2) with an intraventricular balloon and a volumetric cylinder, and (3) with the same balloon and areciprocal pump which could clamp the endsystolic volume. We found consistently that as long as the contractile state was stable the endayatolic pressure-volume relationship curve was largely independent of the loading conditions such as enddiastolic volume and ventricular afterload pressure and also of whether the mode of contraction was isovolumic, auxobaric or physiologically ejecting. When the endsystolic pressure was kept unchanged in the ventricle with a stable contractile state, the intraventricular volume decreased to the same volume as given by the endsystolic pressure-volume relationship and the afterload pressure. When the endsystolic volume was maintained constant, the ventricle developed at the end of systole almost the same pressure as that predicted from the same endsystolic pressure-volume relationship. The endsystolic pressure-volume relationship, therefore, uniquely characterizes the degree of ventricular compression under a given contractile state."} {"id": "PMID:1278224", "title": "On the question of tachyphylaxis to isoproterenol in guinea pigs.", "content": "Isoproterenol (4 mug/kg, i.m.) decreased mortality of conscious guinea pigs to histamine, when histamine was injected 8 min after a single dose. But, when guinea pigs were injected with isoproterenol or saline every 20 min for 5 hr, followed by a histamine challenge 8 (or 120) min later, there was no difference in mortality between the two groups. This failure of repeated doses of isoproterenol to protect guinea pigs (from effects of histamine) may be related to its cardiovascular effects, since control blood pressure decreased significantly more in the isoproterenol group than in the saline group. This hypothesis was supported by the observation that histamine-induced mortality was significantly increased in guinea pigs treated with a vasodilator (minoxidil), whose blood pressure decreased to the same level (54 +/- 5 mm Hg) as that observed after repeated doses of isoproterenol. Tachyphylaxis to heart rate or blood pressure responses of isoproterenol was not observed. 10 repeated additions of isoproterenol to spontaneously beating atria or tracheal strips did not show any tachyphylaxis, nor did 15-20 additions of isoproterenol to perfused lungs.", "contents": "On the question of tachyphylaxis to isoproterenol in guinea pigs. Isoproterenol (4 mug/kg, i.m.) decreased mortality of conscious guinea pigs to histamine, when histamine was injected 8 min after a single dose. But, when guinea pigs were injected with isoproterenol or saline every 20 min for 5 hr, followed by a histamine challenge 8 (or 120) min later, there was no difference in mortality between the two groups. This failure of repeated doses of isoproterenol to protect guinea pigs (from effects of histamine) may be related to its cardiovascular effects, since control blood pressure decreased significantly more in the isoproterenol group than in the saline group. This hypothesis was supported by the observation that histamine-induced mortality was significantly increased in guinea pigs treated with a vasodilator (minoxidil), whose blood pressure decreased to the same level (54 +/- 5 mm Hg) as that observed after repeated doses of isoproterenol. Tachyphylaxis to heart rate or blood pressure responses of isoproterenol was not observed. 10 repeated additions of isoproterenol to spontaneously beating atria or tracheal strips did not show any tachyphylaxis, nor did 15-20 additions of isoproterenol to perfused lungs."} {"id": "PMID:1278225", "title": "Catecholamine release by intracerebral perfusion of 6-hydroxydopamine and desipramine.", "content": "The rate of catecholamine release at perfusion sites in the diencephalon of the unanesthetized rat during the perfusion of a solution of 6-hydroxydopamine (6-OHDA) or desipramine (DMI). Endogenous stores of norepinephrine (NE) and dopamine (DA) were first tagged by the cerebral microinjection of 14C- or 3H-labelled NE or DA. After successive control perfusates were collected with a push-pull cannula system, 6-OHDA, in a concentration of 5.0, 0.5, or 0.1 mg/ml, was perfused at 20-23 mul/min through a site in the rat'e brain. The compound induced a dose-related release of both NE and DA. In control experiments, 6-OHDA exerted a non-specific releasing effect on 3H-inulin which was not dose dependent. In addition, DMI, an NE reuptake inhibitor in a concentration of 10.0, 2.0 or 0.5 mg/ml, was perfused through 23 sites in the brain following the injection of labelled NE. DMI enhanced the recovery of NE in the push-pull effluent at the 10.0 mg/ml concentration only. However, an augmented efflux of 3H-inulin was also observed during the perfusion of the highest concentration of DMI. These results support the view that 6-OHDA releases catecholamines from endogenous storage sites, but also indicate a strong non-specific releasing action of this compound possibly at extracellular or non-catecholaminergic loci.", "contents": "Catecholamine release by intracerebral perfusion of 6-hydroxydopamine and desipramine. The rate of catecholamine release at perfusion sites in the diencephalon of the unanesthetized rat during the perfusion of a solution of 6-hydroxydopamine (6-OHDA) or desipramine (DMI). Endogenous stores of norepinephrine (NE) and dopamine (DA) were first tagged by the cerebral microinjection of 14C- or 3H-labelled NE or DA. After successive control perfusates were collected with a push-pull cannula system, 6-OHDA, in a concentration of 5.0, 0.5, or 0.1 mg/ml, was perfused at 20-23 mul/min through a site in the rat'e brain. The compound induced a dose-related release of both NE and DA. In control experiments, 6-OHDA exerted a non-specific releasing effect on 3H-inulin which was not dose dependent. In addition, DMI, an NE reuptake inhibitor in a concentration of 10.0, 2.0 or 0.5 mg/ml, was perfused through 23 sites in the brain following the injection of labelled NE. DMI enhanced the recovery of NE in the push-pull effluent at the 10.0 mg/ml concentration only. However, an augmented efflux of 3H-inulin was also observed during the perfusion of the highest concentration of DMI. These results support the view that 6-OHDA releases catecholamines from endogenous storage sites, but also indicate a strong non-specific releasing action of this compound possibly at extracellular or non-catecholaminergic loci."} {"id": "PMID:1278226", "title": "Evaluation of the antinociceptive effects of 4, alpha-dimethyl-m-tyramine (H 77/77) in the rat.", "content": "4, alpha-Dimethyl-m-tyramine (H 77/77) has been shown to induce dose dependently antinociceptive activity against 3 parameters: (1) the motor (M), (2) the vocalisation during stimulation (V) and (3) the vocalisation after withdrawal of stimulation (VA) responses. The effect of H 77/77 upon the V and VA pain responses was abolished or reduced by prior treatment with phenoxybenzamine, chlorpromazine, H 44/68, FLA 63, reserpine and protriptyline, and was potentiated by atropine sulphate. It is suggested that H 77/77 may exert is inhibitory effect on painful stimulation predominantly by inhibiting spinal sensory input.", "contents": "Evaluation of the antinociceptive effects of 4, alpha-dimethyl-m-tyramine (H 77/77) in the rat. 4, alpha-Dimethyl-m-tyramine (H 77/77) has been shown to induce dose dependently antinociceptive activity against 3 parameters: (1) the motor (M), (2) the vocalisation during stimulation (V) and (3) the vocalisation after withdrawal of stimulation (VA) responses. The effect of H 77/77 upon the V and VA pain responses was abolished or reduced by prior treatment with phenoxybenzamine, chlorpromazine, H 44/68, FLA 63, reserpine and protriptyline, and was potentiated by atropine sulphate. It is suggested that H 77/77 may exert is inhibitory effect on painful stimulation predominantly by inhibiting spinal sensory input."} {"id": "PMID:1278227", "title": "Gastric acid stimulating action of cysteamine in the rat.", "content": "Cysteamine was previously found to produce duodenal ulcers in rats. In the present study, the effect of cysteamine on gastric secretion was studied. Cysteamine administered by a parenteral or intraduodenal route induced a marked and sustained increase in gastric secretion in conscious and in anesthetized rats. The response to cysteamine or its metabolite, cystamine, appeared gradually and the maximum response was observed in 2 or 3 hr after the administration. The response to cysteamine was completely inhibited by vagotomy and inhibited dose-dependently by atropine methylbromide or hexamethonium. Cysteamine stimulated gastric acid secretion in conscious rats with chronic gastric fistula but not in rats with denervated gastric pouch. Tissue histamine levels in the gastric mucosa, abdominal muscle and whole blood were not affected by cysteamine. These results suggest that a cholinergic mechanism is involved in the gastric secretion induced by cysteamine.", "contents": "Gastric acid stimulating action of cysteamine in the rat. Cysteamine was previously found to produce duodenal ulcers in rats. In the present study, the effect of cysteamine on gastric secretion was studied. Cysteamine administered by a parenteral or intraduodenal route induced a marked and sustained increase in gastric secretion in conscious and in anesthetized rats. The response to cysteamine or its metabolite, cystamine, appeared gradually and the maximum response was observed in 2 or 3 hr after the administration. The response to cysteamine was completely inhibited by vagotomy and inhibited dose-dependently by atropine methylbromide or hexamethonium. Cysteamine stimulated gastric acid secretion in conscious rats with chronic gastric fistula but not in rats with denervated gastric pouch. Tissue histamine levels in the gastric mucosa, abdominal muscle and whole blood were not affected by cysteamine. These results suggest that a cholinergic mechanism is involved in the gastric secretion induced by cysteamine."} {"id": "PMID:1278228", "title": "The effects of holothurin A on the resting membrane potential and conductance of squid axon.", "content": "The effects of a marine toxin, holothurin A, on the electrical properties of squid axon membranes were studied. External application of holothurin A to the intact axon produced an irreversible depolarization of the membrane to nearly zero potential. Internal perfusion of squid axon with holothurin A produced a biphasic depolarization of the membrane. The time course of the depolarization was much shorter with internal application than with external application. The holothurin A-induced depolarization was partially reversed either by reduction of the external sodium concentration to 1 mM or by removal of sodium from both external and internal solutions. The results demonstrate an increase in resting sodium permeability as one of the mechanisms underlying the depolarization by holothurin A. However, external application of tetrodotoxin had no effect on the membrane depolarization. Increase of the resting permeability to potassium is suggested as the additional mechanism of depolarization. A model is developed which predicts this anomalous depolarization.", "contents": "The effects of holothurin A on the resting membrane potential and conductance of squid axon. The effects of a marine toxin, holothurin A, on the electrical properties of squid axon membranes were studied. External application of holothurin A to the intact axon produced an irreversible depolarization of the membrane to nearly zero potential. Internal perfusion of squid axon with holothurin A produced a biphasic depolarization of the membrane. The time course of the depolarization was much shorter with internal application than with external application. The holothurin A-induced depolarization was partially reversed either by reduction of the external sodium concentration to 1 mM or by removal of sodium from both external and internal solutions. The results demonstrate an increase in resting sodium permeability as one of the mechanisms underlying the depolarization by holothurin A. However, external application of tetrodotoxin had no effect on the membrane depolarization. Increase of the resting permeability to potassium is suggested as the additional mechanism of depolarization. A model is developed which predicts this anomalous depolarization."} {"id": "PMID:1278229", "title": "Effects of morphine and barbiturate on the SI and SII potentials evoked by tooth pulp stimulation of rats.", "content": "The effects of morphine and barbiturate on the evoked potentials recorded from the primary and secondary somatic sensory areas of rats were investigated. The electric stimulation of contra- and ipsilateral tooth pulp (CTP and ITP) was used. The afferent impulse from dental pulp projected to the sensory face areas I and II (SI and SII). Morphine in doses of 2.5-10 mg/kg definitely inhibited SI and SII potentials evoked by CTP stimulation. Morphine also inhibited SII potentials evoked by ITP stimulation, while it rather enhanced SI potentials evoked by ITP stimulation. Pentobarbital sodium in doses of 4-16 mg/kg tended to inhibit SI potentials, but showed no effect or rather an enhancement on SII potentials evoked by CTP stimulation. Pentobarbital sodium enhanced SI and SII potentials evoked by ITP stimulation. In a large dose of 32 mg/kg, pentobarbital sodium inhibited SI and SII potentials evoked by ITP and CTP stimulations. The results suggest that SII is more closely related to the analgesia due to morphine than is SI.", "contents": "Effects of morphine and barbiturate on the SI and SII potentials evoked by tooth pulp stimulation of rats. The effects of morphine and barbiturate on the evoked potentials recorded from the primary and secondary somatic sensory areas of rats were investigated. The electric stimulation of contra- and ipsilateral tooth pulp (CTP and ITP) was used. The afferent impulse from dental pulp projected to the sensory face areas I and II (SI and SII). Morphine in doses of 2.5-10 mg/kg definitely inhibited SI and SII potentials evoked by CTP stimulation. Morphine also inhibited SII potentials evoked by ITP stimulation, while it rather enhanced SI potentials evoked by ITP stimulation. Pentobarbital sodium in doses of 4-16 mg/kg tended to inhibit SI potentials, but showed no effect or rather an enhancement on SII potentials evoked by CTP stimulation. Pentobarbital sodium enhanced SI and SII potentials evoked by ITP stimulation. In a large dose of 32 mg/kg, pentobarbital sodium inhibited SI and SII potentials evoked by ITP and CTP stimulations. The results suggest that SII is more closely related to the analgesia due to morphine than is SI."} {"id": "PMID:1278230", "title": "Inhibition and potentiation of apomorphine-induced hypermotility in rats by neuroleptics.", "content": "The effect of apomorphine (ap) was investigated in rats kept in a familiar cage; 0.25-5 mg/kg s.c. produced a short-lasting, abnormal hypermotility consisting mainly of locomotion and sniffing without grooming. Ap was administered to rate pretreated s.c. with various drugs. Ap hypermotility was antagonized by 12 neuroleptics from different chemical groups. The ap inhibitory effect of 5 neuroleptics was decreased when the interval between pretreatment and ap administration was increased from 0.5 to 4 hr. Clozapine was the only neuroleptic showing no inhibition but potentiation at 4 hr. Mepazine, a phenothiazine lacking antipsychotic effects, as well as the NA receptor blockers aceperone and phenoxybenzamine, did not inhibit ap hypermotility. Ap was also given 24 hr after haloperidol and clozapine. At this time both neuroleptics showed ap potentiation. The ap inhibition and potentiation after a single administration of the neuroleptics is presumable due to selective blockade and subsequent supersensitivity of some DA receptors.", "contents": "Inhibition and potentiation of apomorphine-induced hypermotility in rats by neuroleptics. The effect of apomorphine (ap) was investigated in rats kept in a familiar cage; 0.25-5 mg/kg s.c. produced a short-lasting, abnormal hypermotility consisting mainly of locomotion and sniffing without grooming. Ap was administered to rate pretreated s.c. with various drugs. Ap hypermotility was antagonized by 12 neuroleptics from different chemical groups. The ap inhibitory effect of 5 neuroleptics was decreased when the interval between pretreatment and ap administration was increased from 0.5 to 4 hr. Clozapine was the only neuroleptic showing no inhibition but potentiation at 4 hr. Mepazine, a phenothiazine lacking antipsychotic effects, as well as the NA receptor blockers aceperone and phenoxybenzamine, did not inhibit ap hypermotility. Ap was also given 24 hr after haloperidol and clozapine. At this time both neuroleptics showed ap potentiation. The ap inhibition and potentiation after a single administration of the neuroleptics is presumable due to selective blockade and subsequent supersensitivity of some DA receptors."} {"id": "PMID:1278231", "title": "Effect of intracerebroventricular 5,6-dihydroxytryptamine on blood pressure of spontaneously hypertensive rats.", "content": "The effects of intracerebroventricular injections of 5,6-DHT on the development and maintenance of hypertension in spontaneously hypertensive rats has been investigated. 5,6-DHT, injected into 6 week old rats, retarded the development of hypertension for at least 6 weeks; this effect was not accompanied by inhibition of the pressor response produced by stimulation of the total peripheral sympathetic outflow. 5,6-DHT, injected into 14-15 week old rats with established hypertension, produced a short-lived fall in blood pressure. These findings suggest that central 5-HT neurones are involved in the development of hypertension in spontaneously hypertensive rats.", "contents": "Effect of intracerebroventricular 5,6-dihydroxytryptamine on blood pressure of spontaneously hypertensive rats. The effects of intracerebroventricular injections of 5,6-DHT on the development and maintenance of hypertension in spontaneously hypertensive rats has been investigated. 5,6-DHT, injected into 6 week old rats, retarded the development of hypertension for at least 6 weeks; this effect was not accompanied by inhibition of the pressor response produced by stimulation of the total peripheral sympathetic outflow. 5,6-DHT, injected into 14-15 week old rats with established hypertension, produced a short-lived fall in blood pressure. These findings suggest that central 5-HT neurones are involved in the development of hypertension in spontaneously hypertensive rats."} {"id": "PMID:1278232", "title": "Separation of inhibiting and stimulating effects of morphine on self-stimulation behaviour by intracerebral microinjections.", "content": "The effects on self-stimulation behaviour of 5 mug morphine HCl applied into the ventricular system and into different areas throughout the brain were studied. Injections into the ventricular system and in areas intermediate between the posterior hypothalamus and the periaqueductal grey matter had biphasic effects: an inhibition followed by an excitation. Injections into the posterior hypothalamus resulted in increased self-stimulation whereas injections into the periaqueductal grey matter and into the locus coeruleus were only inhibiting.", "contents": "Separation of inhibiting and stimulating effects of morphine on self-stimulation behaviour by intracerebral microinjections. The effects on self-stimulation behaviour of 5 mug morphine HCl applied into the ventricular system and into different areas throughout the brain were studied. Injections into the ventricular system and in areas intermediate between the posterior hypothalamus and the periaqueductal grey matter had biphasic effects: an inhibition followed by an excitation. Injections into the posterior hypothalamus resulted in increased self-stimulation whereas injections into the periaqueductal grey matter and into the locus coeruleus were only inhibiting."} {"id": "PMID:1278233", "title": "Centrally mediated antihypertensive and bradycardic effects of methysergide in spontaneously hypertensive rats.", "content": "Methysergide caused dose-dependent reductions in systolic blood pressure and heart rate of unanesthetized SHR, whereas cyproheptadine was ineffective. In pithed SHR pretreated with methysergide or cyproheptadine, pressor responses to 5-HT were abolished. Responses to sympathetic nerve stimulation were unaltered by methysergide, whereas cyproheptadine slightly reduced them. Both drugs enhanced pressor responses to norepinephrine. Failure to identify a peripheral mechanism for the antihypertensive action of methysergide suggests that the effect may be centrally mediated but not reliant upon serotonin receptor blockade.", "contents": "Centrally mediated antihypertensive and bradycardic effects of methysergide in spontaneously hypertensive rats. Methysergide caused dose-dependent reductions in systolic blood pressure and heart rate of unanesthetized SHR, whereas cyproheptadine was ineffective. In pithed SHR pretreated with methysergide or cyproheptadine, pressor responses to 5-HT were abolished. Responses to sympathetic nerve stimulation were unaltered by methysergide, whereas cyproheptadine slightly reduced them. Both drugs enhanced pressor responses to norepinephrine. Failure to identify a peripheral mechanism for the antihypertensive action of methysergide suggests that the effect may be centrally mediated but not reliant upon serotonin receptor blockade."} {"id": "PMID:1278234", "title": "Behavioural, electrocortical and body temperature effects of cholera toxin.", "content": "In young chicks intrahypothalamic infusion of cholera toxin produced a dramatic and dose-dependent increase in motor activity. Similar effects were also obtained in adult fowls after injection of cholera toxin into the third cerebral ventricle, the hypothalamus or the paleostriatum augmentatum. Electrocortical changes consisted of a slight desynchronization during the hypermotor activity and were preceded, when the highest intraventricular doses were used, by a short period of slower frequency and higher amplitude potentials. Intraventricular and intrahypothalamic but not intrastriatal injection of cholera toxin produced a typical biphasic hyperthermic response.", "contents": "Behavioural, electrocortical and body temperature effects of cholera toxin. In young chicks intrahypothalamic infusion of cholera toxin produced a dramatic and dose-dependent increase in motor activity. Similar effects were also obtained in adult fowls after injection of cholera toxin into the third cerebral ventricle, the hypothalamus or the paleostriatum augmentatum. Electrocortical changes consisted of a slight desynchronization during the hypermotor activity and were preceded, when the highest intraventricular doses were used, by a short period of slower frequency and higher amplitude potentials. Intraventricular and intrahypothalamic but not intrastriatal injection of cholera toxin produced a typical biphasic hyperthermic response."} {"id": "PMID:1278235", "title": "Alpha-noradrenergic modulation of hypothalamic self-stimulation: studies employing clonidine, 1-phenylephrine and alpha-methyl-p-tyrosine.", "content": "An alpha-noradrenergic substrate of rewarding intracranial stimulation (ICS) has been hypothesized based on the observation that the alpha-antagonist phentolamine produced an inhibition of self-stimulation. The present experiment investigated the effects on hypothalamic self-stimulation of the alpha agonist clonidine in normal and in catecholamine-depleted rats. Using a shuttle-box technique that provides a rate-independent index of the rewarding and aversive components of ICS, it was demonstrated that clonidine produces a dose-dependent inhibition of reward that is clearly dissociable from any non-specific effects of the drug. The ineffectiveness of the peripheral alpha-agonist 1-phenylephrine indicates that the inhibition of reward produced by clonidine is mediated centrally. Clonidine and the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine act together in a synergistic manner to greatly increase the magnitude and prolong the duration of the inhibition of reward while leaving the aversive component unaffected. These data are interpreted as supporting an alpha-noradrenergic basis of ICS reward while indicating that the aversive component of ICS is essentially independent of noradrenergic transmission.", "contents": "Alpha-noradrenergic modulation of hypothalamic self-stimulation: studies employing clonidine, 1-phenylephrine and alpha-methyl-p-tyrosine. An alpha-noradrenergic substrate of rewarding intracranial stimulation (ICS) has been hypothesized based on the observation that the alpha-antagonist phentolamine produced an inhibition of self-stimulation. The present experiment investigated the effects on hypothalamic self-stimulation of the alpha agonist clonidine in normal and in catecholamine-depleted rats. Using a shuttle-box technique that provides a rate-independent index of the rewarding and aversive components of ICS, it was demonstrated that clonidine produces a dose-dependent inhibition of reward that is clearly dissociable from any non-specific effects of the drug. The ineffectiveness of the peripheral alpha-agonist 1-phenylephrine indicates that the inhibition of reward produced by clonidine is mediated centrally. Clonidine and the catecholamine synthesis inhibitor alpha-methyl-p-tyrosine act together in a synergistic manner to greatly increase the magnitude and prolong the duration of the inhibition of reward while leaving the aversive component unaffected. These data are interpreted as supporting an alpha-noradrenergic basis of ICS reward while indicating that the aversive component of ICS is essentially independent of noradrenergic transmission."} {"id": "PMID:1278236", "title": "Prevention and reversal of tolerance to barbiturates by intraventricular injection of hemicholinium-3.", "content": "Intracerebroventricular (i.c.v.) injection of phenobarbital, 800 mug, or intraperitoneal (i.p.) injection of hexobarbital, 100 mg/kg, into rats resulted in a loss of righting reflex lasting 15.4 +/- 0.2 min and 20.7 +/- 0.7 min, respectively. A 40-60% reduction in this response was obtained following administration of phenobarbital either i.c.v. (800 mug 4 times daily) or i.p. (80 mg/kg/day) for 4 days. Although these treatments also increased hepatic mixed function oxidase activity, this enzyme induction was shown to be unrelated to the development of tolerance to loss of righting reflex. I.c.v. injection of hemicholinium-3 (HC-3) in doses which reduce brain acetylcholine levels (4-20 mug) profoundly affected tolerance to the central depressant effect of the barbiturates. Thus, depending upon the time of administration, HC-3 either retarded or prevented development of this tolerance. Moreover, if tolerance was allowed to progress normally, administration of HC-3 on day 4 or 5 returned the duration of the loss of righting reflex toward normal values. HC-3 did not influence either the duration of this response in non-tolerant rats or the induction of the hepatic mixed function oxidase activity. These results suggest that brain ACh plays an important role in the development and maintenance of tolerance to the central depressant effects of barbiturates.", "contents": "Prevention and reversal of tolerance to barbiturates by intraventricular injection of hemicholinium-3. Intracerebroventricular (i.c.v.) injection of phenobarbital, 800 mug, or intraperitoneal (i.p.) injection of hexobarbital, 100 mg/kg, into rats resulted in a loss of righting reflex lasting 15.4 +/- 0.2 min and 20.7 +/- 0.7 min, respectively. A 40-60% reduction in this response was obtained following administration of phenobarbital either i.c.v. (800 mug 4 times daily) or i.p. (80 mg/kg/day) for 4 days. Although these treatments also increased hepatic mixed function oxidase activity, this enzyme induction was shown to be unrelated to the development of tolerance to loss of righting reflex. I.c.v. injection of hemicholinium-3 (HC-3) in doses which reduce brain acetylcholine levels (4-20 mug) profoundly affected tolerance to the central depressant effect of the barbiturates. Thus, depending upon the time of administration, HC-3 either retarded or prevented development of this tolerance. Moreover, if tolerance was allowed to progress normally, administration of HC-3 on day 4 or 5 returned the duration of the loss of righting reflex toward normal values. HC-3 did not influence either the duration of this response in non-tolerant rats or the induction of the hepatic mixed function oxidase activity. These results suggest that brain ACh plays an important role in the development and maintenance of tolerance to the central depressant effects of barbiturates."} {"id": "PMID:1278237", "title": "The effects of chronic reserpine treatment on the contractile activity of the isolated vas deferens of the guinea pig.", "content": "Chronic reserpine treatment of guinea pigs during 5 days (1 mg/kg/day) induces postjunctional supersensitivity in the isolated vas deferens. It has been previously proposed that postjunctional supersensitivity occurs as a result of an ionic and/or membrane mechanism. Contrasting with previous observations in vascular smooth muscle the present results demonstrate that chronic reserpine treatment did not increase the sensitivity of the depolarized vas deferens to calcium. Experiments on drug responsiveness show that the supersensitive depolarized tissues have a greater and slower rate of loss of responsiveness than do control vasa deferentia. However, in a Ca2+-free Krebs solution responsiveness of supersensitive vasa deferentia did not differ from that of control tissues. These findings suggest that, in the guinea-pig vas deferens, reserpine-induced supersensitivity could be at least partially dependent on the increased availability of a calcium store(s) probably located at the cell membrane and/or cytoplasmic compartments.", "contents": "The effects of chronic reserpine treatment on the contractile activity of the isolated vas deferens of the guinea pig. Chronic reserpine treatment of guinea pigs during 5 days (1 mg/kg/day) induces postjunctional supersensitivity in the isolated vas deferens. It has been previously proposed that postjunctional supersensitivity occurs as a result of an ionic and/or membrane mechanism. Contrasting with previous observations in vascular smooth muscle the present results demonstrate that chronic reserpine treatment did not increase the sensitivity of the depolarized vas deferens to calcium. Experiments on drug responsiveness show that the supersensitive depolarized tissues have a greater and slower rate of loss of responsiveness than do control vasa deferentia. However, in a Ca2+-free Krebs solution responsiveness of supersensitive vasa deferentia did not differ from that of control tissues. These findings suggest that, in the guinea-pig vas deferens, reserpine-induced supersensitivity could be at least partially dependent on the increased availability of a calcium store(s) probably located at the cell membrane and/or cytoplasmic compartments."} {"id": "PMID:1278238", "title": "DPAVP: a vasopressin analog with selective microvascular and RES actions for the treatment of circulatory shock in rats.", "content": "The present study indicates that: (a) local administration of low concentrations of an analog of vasopressin, 1-deamino-[2-phenylalanine, 8-arginine]-vasopressin (DPAVP), constricts venules in the rat splanchnic terminal vascular bed of normal animals, unlike that seen for catecholamines; (b) maximal concentrations of DPAVP narrow but do not occlude both arterioles and venules: (c) microscopic muscular venules (31-39 mu i.d.) do not narrow more than 20% in response to the vasopressin analog DPAVP; and (d) terminal arterioles (17-23 mu i.d.) do not narrow more than 50% in response to DPAVP. Systemic administration of DPAVP to rats subjected to hemorrhage or bowel ischemia shock more than doubles survival rates over control rats receiving Ringer solution. Infusion of DPAVP produces a dose-dependent effect on arterial blood pressure, microscopic capacitance vessels, large arterioles and small arteries. In addition, i.v. administration of DPAVP: (a) returns arterial hematocrit towards normal after shock; and (b) regenerates and sustains vasomotion and venular tone, decreases microvascular hyperreactivity characteristic of shock syndromes, restores constricted arteriolar lumen sizes towards normal, predisposes to a splanchnic microbed virtually free of stasis, petechiae and leukocytic sticking, and restores capillary perfusion and outflow to near-normal. Further, DPAVP effectively restores the early reticuloendothelial system (RES) phagocytic depression, characteristic of shock syndromes, to normal; the latter eventuating in RES hyper-phagocytic activity. These findings indicate it is possible to synthesize vasoactive molecules which: (a) exert selective microvascular and RES phagocytic effects; and (b) are highly beneficial in the therapy of low-flow states, at least in rats.", "contents": "DPAVP: a vasopressin analog with selective microvascular and RES actions for the treatment of circulatory shock in rats. The present study indicates that: (a) local administration of low concentrations of an analog of vasopressin, 1-deamino-[2-phenylalanine, 8-arginine]-vasopressin (DPAVP), constricts venules in the rat splanchnic terminal vascular bed of normal animals, unlike that seen for catecholamines; (b) maximal concentrations of DPAVP narrow but do not occlude both arterioles and venules: (c) microscopic muscular venules (31-39 mu i.d.) do not narrow more than 20% in response to the vasopressin analog DPAVP; and (d) terminal arterioles (17-23 mu i.d.) do not narrow more than 50% in response to DPAVP. Systemic administration of DPAVP to rats subjected to hemorrhage or bowel ischemia shock more than doubles survival rates over control rats receiving Ringer solution. Infusion of DPAVP produces a dose-dependent effect on arterial blood pressure, microscopic capacitance vessels, large arterioles and small arteries. In addition, i.v. administration of DPAVP: (a) returns arterial hematocrit towards normal after shock; and (b) regenerates and sustains vasomotion and venular tone, decreases microvascular hyperreactivity characteristic of shock syndromes, restores constricted arteriolar lumen sizes towards normal, predisposes to a splanchnic microbed virtually free of stasis, petechiae and leukocytic sticking, and restores capillary perfusion and outflow to near-normal. Further, DPAVP effectively restores the early reticuloendothelial system (RES) phagocytic depression, characteristic of shock syndromes, to normal; the latter eventuating in RES hyper-phagocytic activity. These findings indicate it is possible to synthesize vasoactive molecules which: (a) exert selective microvascular and RES phagocytic effects; and (b) are highly beneficial in the therapy of low-flow states, at least in rats."} {"id": "PMID:1278239", "title": "BRL 8242 (2-[2-benzimidazolyl]-amino-2-imidazoline dihydrochloride), a new inhibitor of dopamine-beta-hydroxylase with antihypertensive activity.", "content": "BRL 8242 (2-[2-benzimidazolyl]-amino-2-imidazoline dihydrochloride) was found to inhibit dopamine-beta-hydroxylase in vitro and in vivo and to have antihypertensive activity. The effect on dopamine-beta-hydroxylase in vitro was shown by inhibition of the conversion of phenylethylamine to phenylethanolamine, using enzyme extracted from rat adrenals. In vivo, BRL 8242 inhibited 3H-noradrenaline but not 3H-dopamine biosynthesis from 3H-L-dopa in rat brain. Furthermore, the compound lowered endogenous noradrenaline levels in both rat brain and heart whilst increasing the concentration of brain dopamine. In both metacorticoid hypertensive and normotensive rats, BRL 8242 lowered blood pressure. This response was dose related and correlated well with the reduction of endogenous noradrenaline in the tissues examined. It is therefore suggested that the inhibition of dopamine-beta-hydroxylase by BRL 8242 may account for its blood pressure lowering activity.", "contents": "BRL 8242 (2-[2-benzimidazolyl]-amino-2-imidazoline dihydrochloride), a new inhibitor of dopamine-beta-hydroxylase with antihypertensive activity. BRL 8242 (2-[2-benzimidazolyl]-amino-2-imidazoline dihydrochloride) was found to inhibit dopamine-beta-hydroxylase in vitro and in vivo and to have antihypertensive activity. The effect on dopamine-beta-hydroxylase in vitro was shown by inhibition of the conversion of phenylethylamine to phenylethanolamine, using enzyme extracted from rat adrenals. In vivo, BRL 8242 inhibited 3H-noradrenaline but not 3H-dopamine biosynthesis from 3H-L-dopa in rat brain. Furthermore, the compound lowered endogenous noradrenaline levels in both rat brain and heart whilst increasing the concentration of brain dopamine. In both metacorticoid hypertensive and normotensive rats, BRL 8242 lowered blood pressure. This response was dose related and correlated well with the reduction of endogenous noradrenaline in the tissues examined. It is therefore suggested that the inhibition of dopamine-beta-hydroxylase by BRL 8242 may account for its blood pressure lowering activity."} {"id": "PMID:1278240", "title": "Placental transfer of central nervous system depressants in sheep.", "content": "Continuous monitoring of the foetal electrocorticogram, eye movements and heart rate in ewes during the last month of gestation showed rapid placental transfer from the mother to the foetus of phenothiazine derivatives (acepromazine maleate), short-acting barbiturates (thiopental sodium) and narcotic analgesics (meperidine). Acepromazine and thiopental partially disrupted the foetal sleep cycle by synchronization of the ECoG for 1-2 h but increased the heart rate for 2-3 h. The effects of meperidine were similar but lasted only 5-10 min for the ECoG and less than 0.5 h for the heart rate.", "contents": "Placental transfer of central nervous system depressants in sheep. Continuous monitoring of the foetal electrocorticogram, eye movements and heart rate in ewes during the last month of gestation showed rapid placental transfer from the mother to the foetus of phenothiazine derivatives (acepromazine maleate), short-acting barbiturates (thiopental sodium) and narcotic analgesics (meperidine). Acepromazine and thiopental partially disrupted the foetal sleep cycle by synchronization of the ECoG for 1-2 h but increased the heart rate for 2-3 h. The effects of meperidine were similar but lasted only 5-10 min for the ECoG and less than 0.5 h for the heart rate."} {"id": "PMID:1278241", "title": "Intragastric NaHCO3 perfusion and vagal-induced ulcer formation in the rat stomach.", "content": "The effects of electrical vagal stimulation on gastric acid output and ulcer formation were studied in rats intragastrically perfused with saline or NaHCO3 solutions. Vagal stimulation produced a 100% incidence of glandular lesions and a significant increase in total acid output in saline-perfused stomachs. Antacid perfusion failed to prevent ulcer formation despite complete neutralization of the increased acid output. It is considered that vagal-induced gastric glandular lesions are not acid dependent.", "contents": "Intragastric NaHCO3 perfusion and vagal-induced ulcer formation in the rat stomach. The effects of electrical vagal stimulation on gastric acid output and ulcer formation were studied in rats intragastrically perfused with saline or NaHCO3 solutions. Vagal stimulation produced a 100% incidence of glandular lesions and a significant increase in total acid output in saline-perfused stomachs. Antacid perfusion failed to prevent ulcer formation despite complete neutralization of the increased acid output. It is considered that vagal-induced gastric glandular lesions are not acid dependent."} {"id": "PMID:1278242", "title": "Dopamine metabolism in the nucleus accumbens: the effect of clozapine.", "content": "Dopamine metabolism in the nucleus accumbens of the rat was studied by gas chromatographic quantitation of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The ratio of DOPAC/HVA in the nucleus accumbens was significantly greater than the same ratio in the striatum. Dose-response curves for the increase in DOPAC and HVA in the nucleus accumbens and striatum 2 h after clozapine were generated. The effect of clozapine on dopamine metabolism was similar in both structures.", "contents": "Dopamine metabolism in the nucleus accumbens: the effect of clozapine. Dopamine metabolism in the nucleus accumbens of the rat was studied by gas chromatographic quantitation of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). The ratio of DOPAC/HVA in the nucleus accumbens was significantly greater than the same ratio in the striatum. Dose-response curves for the increase in DOPAC and HVA in the nucleus accumbens and striatum 2 h after clozapine were generated. The effect of clozapine on dopamine metabolism was similar in both structures."} {"id": "PMID:1278243", "title": "Calcium influx and postjunctional supersensitivity in guinea pig aortic strips.", "content": "Both reserpine and 6-hydroxydopamine (6-OHDA) pretreatment potentiated the sensitivity of guinea pig aortic strips to norepinephrine (NE), barium, methoxamine and potassium indicating postjunctional supersensitivity. However, cocaine treatmetn only potentiated the NE response indicating prejunctional supersensitivity. 6-OHDA and reserpine-induced supersensitivity but not cocaine-induced supersensitivity was accompanied by an increase in 45Ca influx.", "contents": "Calcium influx and postjunctional supersensitivity in guinea pig aortic strips. Both reserpine and 6-hydroxydopamine (6-OHDA) pretreatment potentiated the sensitivity of guinea pig aortic strips to norepinephrine (NE), barium, methoxamine and potassium indicating postjunctional supersensitivity. However, cocaine treatmetn only potentiated the NE response indicating prejunctional supersensitivity. 6-OHDA and reserpine-induced supersensitivity but not cocaine-induced supersensitivity was accompanied by an increase in 45Ca influx."} {"id": "PMID:1278244", "title": "Caffeine and KC1 contracture in cat myocardium.", "content": "Caffeine increases the force of contracture induced in cat myocardium by exposure to 140 mM KC1 in isotonic Tyrode solution. The effect of caffeine does not require prior exposure to the drug, develops rapidly, and is partially antagonized by procaine but not by verapamil. These results suggest that caffeine acts on depolarized sarcolemma to release a sarcolemmal calcium pool.", "contents": "Caffeine and KC1 contracture in cat myocardium. Caffeine increases the force of contracture induced in cat myocardium by exposure to 140 mM KC1 in isotonic Tyrode solution. The effect of caffeine does not require prior exposure to the drug, develops rapidly, and is partially antagonized by procaine but not by verapamil. These results suggest that caffeine acts on depolarized sarcolemma to release a sarcolemmal calcium pool."} {"id": "PMID:1278245", "title": "Quantitative comparison of the analgesic and anti-inflammatory activities of aspirin, phenacetin and acetaminophen in rodents.", "content": "The mild analgesic activities of aspirin, phenacetin and acetaminophen have been compared in the trypsin, kaolin and carrageenan hyperalgesic assays as well as in the acetic acid writhing test. The trypsin and kaolin hyperalgesic assays were designed to be unaffected by drugs with anti-inflammatory activity. Aspirin and acetaminophen were inactive in these two tests at dose levels devoid of side effects. Phenacetin was active in the trypsin and kaolin assays with oral ED50's of 114 +/- 36.2 and 107 +/- 11.5 mg/kg, respectively. Non-steroidal anti-inflammatory drugs as well as phenacetin and acetaminophen were active in the acetic acid writhing and carrageenan hyperalgesic assays. This led to evaluation of phenacetin and acetaminophen as anti-inflammatory agents. Both of these latter drugs were active in the carrageenan pleurisy and adjuvant arthritis models of inflammation. In all studies phenacetin was equipotent to or more potent than acetaminophen. The data suggest that the analgesia produced by aspirin and acetaminophen results from their anti-inflammatory activity whereas the analgesia produced by phenacetin has two components, one dependent on and one independent of anti-inflammatory activity.", "contents": "Quantitative comparison of the analgesic and anti-inflammatory activities of aspirin, phenacetin and acetaminophen in rodents. The mild analgesic activities of aspirin, phenacetin and acetaminophen have been compared in the trypsin, kaolin and carrageenan hyperalgesic assays as well as in the acetic acid writhing test. The trypsin and kaolin hyperalgesic assays were designed to be unaffected by drugs with anti-inflammatory activity. Aspirin and acetaminophen were inactive in these two tests at dose levels devoid of side effects. Phenacetin was active in the trypsin and kaolin assays with oral ED50's of 114 +/- 36.2 and 107 +/- 11.5 mg/kg, respectively. Non-steroidal anti-inflammatory drugs as well as phenacetin and acetaminophen were active in the acetic acid writhing and carrageenan hyperalgesic assays. This led to evaluation of phenacetin and acetaminophen as anti-inflammatory agents. Both of these latter drugs were active in the carrageenan pleurisy and adjuvant arthritis models of inflammation. In all studies phenacetin was equipotent to or more potent than acetaminophen. The data suggest that the analgesia produced by aspirin and acetaminophen results from their anti-inflammatory activity whereas the analgesia produced by phenacetin has two components, one dependent on and one independent of anti-inflammatory activity."} {"id": "PMID:1278246", "title": "Modification by manganese ions and verapamil of the responses of the atrioventricular node to norepinephrine.", "content": "In isolated and cross-circulated canine A-V node preparations single injections of Mn2+ (1-30 mumol) and verapamil (0.3-10 nmol) into the posterior septal artery (PSA) caused a dose-dependent increase in the A-V conduction time and, in large doses, produced A-V conduction block. The A-V conduction time increased by Mn2+ and verapamil is resotred by 1-norepinephrine (1-NE) injected into the PSA. The A-V nodal tachycardia induced by 1-NE is suppressed by Mn2+ but not by verapamil. These indicate the following: (1) the slow Ca2+ channel plays an important role in A-V conduction; (2) the positive dromotropic response of the A-V node to 1-NE may have some relations to the Ca2+ channel; (3) the A-V nodal tachycardia induced by 1-NE may be mediated by the Ca2+ channel. Possible causes which produced differences between Mn2+ and verapamil in the effects in antagonizing the 1-NE-induced A-V nodal tachycardia are discussed.", "contents": "Modification by manganese ions and verapamil of the responses of the atrioventricular node to norepinephrine. In isolated and cross-circulated canine A-V node preparations single injections of Mn2+ (1-30 mumol) and verapamil (0.3-10 nmol) into the posterior septal artery (PSA) caused a dose-dependent increase in the A-V conduction time and, in large doses, produced A-V conduction block. The A-V conduction time increased by Mn2+ and verapamil is resotred by 1-norepinephrine (1-NE) injected into the PSA. The A-V nodal tachycardia induced by 1-NE is suppressed by Mn2+ but not by verapamil. These indicate the following: (1) the slow Ca2+ channel plays an important role in A-V conduction; (2) the positive dromotropic response of the A-V node to 1-NE may have some relations to the Ca2+ channel; (3) the A-V nodal tachycardia induced by 1-NE may be mediated by the Ca2+ channel. Possible causes which produced differences between Mn2+ and verapamil in the effects in antagonizing the 1-NE-induced A-V nodal tachycardia are discussed."} {"id": "PMID:1278247", "title": "The electrodermal response as a model for central sympathetic reactivity: the action of clonidine.", "content": "Electrodermal responses (EDR) were evoked centrally by stimulation of reactive loci in the posterior hypothalamus and peripherally by stimulation of the distal portion of the sectioned median or ulnar nerve. Moderate doses of clonidine (3-30 mug/kg, i.v.) reduced the amplitude of the centrally evoked EDR while having no effect on the peripherally evoked responses. This central action of clonidine occurred concomitantly with the clonidine-induced bradycardia and hypotension. Administration of clonidine shifted the centrally evoked EDR frequency-response curve to the right in a dose related manner at 3, 10 and 30 mu/kg, i.v. 1 mug/kg was without effect on these responses. This central depressant action of clonidine was partially reversed following administration of yohimbine (0.5-1.0 mug/kg, i.v.). These results suggest that clonidine inhibits central reactivity in this sympathetic-cholinergic system in a manner analogous to its action on other sympathetic systems, and that a central adrenergic inhibitory mechanism may be involved.", "contents": "The electrodermal response as a model for central sympathetic reactivity: the action of clonidine. Electrodermal responses (EDR) were evoked centrally by stimulation of reactive loci in the posterior hypothalamus and peripherally by stimulation of the distal portion of the sectioned median or ulnar nerve. Moderate doses of clonidine (3-30 mug/kg, i.v.) reduced the amplitude of the centrally evoked EDR while having no effect on the peripherally evoked responses. This central action of clonidine occurred concomitantly with the clonidine-induced bradycardia and hypotension. Administration of clonidine shifted the centrally evoked EDR frequency-response curve to the right in a dose related manner at 3, 10 and 30 mu/kg, i.v. 1 mug/kg was without effect on these responses. This central depressant action of clonidine was partially reversed following administration of yohimbine (0.5-1.0 mug/kg, i.v.). These results suggest that clonidine inhibits central reactivity in this sympathetic-cholinergic system in a manner analogous to its action on other sympathetic systems, and that a central adrenergic inhibitory mechanism may be involved."} {"id": "PMID:1278248", "title": "A double fatality with children due to fumigated wheat.", "content": "Two children, four and two years old, played on top of wheat, that had been fumigated with malathion, pyrethrum and phosphine. Both died within 18 hours. Because after the autopsy, death could not be attributed to any organic or violent cause, a toxicological analysis was carried out. No drugs, except alcohol, was detected. Those results were attributed to hydrolysis of malathion, yielding two molecules of ethanol. As this was an indirect proof of malathion ingestion, it was assumed that phosphine had been ingested as well and that consequently this was the cause of death, because it is much more toxic than malathion and because it was continuously generated from not completely dissolved aluminiumphosphide tablets, while the children were still playing.", "contents": "A double fatality with children due to fumigated wheat. Two children, four and two years old, played on top of wheat, that had been fumigated with malathion, pyrethrum and phosphine. Both died within 18 hours. Because after the autopsy, death could not be attributed to any organic or violent cause, a toxicological analysis was carried out. No drugs, except alcohol, was detected. Those results were attributed to hydrolysis of malathion, yielding two molecules of ethanol. As this was an indirect proof of malathion ingestion, it was assumed that phosphine had been ingested as well and that consequently this was the cause of death, because it is much more toxic than malathion and because it was continuously generated from not completely dissolved aluminiumphosphide tablets, while the children were still playing."} {"id": "PMID:1278249", "title": "[Determination of lead by atomic absorption spectrophotometry with regard to toxicology research].", "content": "The toxicity of lead in the human environment is acquiring a growing interest which lead us to choose a quick, precise, sensitive and specific method able to perform number of measurements. Thanks to the survey consisting in a dosage of lead by atomic-absorption spectrometric, we are able to confirm the advantages and superiority of such a method and to employ it for the toxicologic research of lead in food, water, industrial atmosphere, and biological liquids.", "contents": "[Determination of lead by atomic absorption spectrophotometry with regard to toxicology research]. The toxicity of lead in the human environment is acquiring a growing interest which lead us to choose a quick, precise, sensitive and specific method able to perform number of measurements. Thanks to the survey consisting in a dosage of lead by atomic-absorption spectrometric, we are able to confirm the advantages and superiority of such a method and to employ it for the toxicologic research of lead in food, water, industrial atmosphere, and biological liquids."} {"id": "PMID:1278250", "title": "[Toxic effects of methoxy-ethyl-mercury in the quail: influence of fasting].", "content": "Quails fed methoxy-ethyl-mercury-treated wheat (20 ppm of Hg) during 10 or 20 days, have been submitted to a three-day fasting following contamination. The test proved to be lethal for a number of intoxicated animals but not for controls. Mercury clearance was modified by anorexia; following fasting, there was a redistribution of the metal, with high concentrations in the liver and kidneys. According to the results of a blood survey uric acid, urea and T. G. O. levels appeared to be the most altered parameters. Transient high blood uric acid levels in intoxicated and anorectic animals could be attributed to kidney dysfunctioning. A possible effect of methoxy-ethyl-mercury on neoglycogenesis was discussed.", "contents": "[Toxic effects of methoxy-ethyl-mercury in the quail: influence of fasting]. Quails fed methoxy-ethyl-mercury-treated wheat (20 ppm of Hg) during 10 or 20 days, have been submitted to a three-day fasting following contamination. The test proved to be lethal for a number of intoxicated animals but not for controls. Mercury clearance was modified by anorexia; following fasting, there was a redistribution of the metal, with high concentrations in the liver and kidneys. According to the results of a blood survey uric acid, urea and T. G. O. levels appeared to be the most altered parameters. Transient high blood uric acid levels in intoxicated and anorectic animals could be attributed to kidney dysfunctioning. A possible effect of methoxy-ethyl-mercury on neoglycogenesis was discussed."} {"id": "PMID:1278251", "title": "Toxicological studies of photosensitizer agents and photodegradable polyolefins.", "content": "The authors report the results of a series of toxicological tests conducted on plastic materials (polyethylene) activated with tetraphenylbutadiene (TPB) an additive recently proposed as a sensitizer capable of photodegrading plastic materials. The toxic effects of polyethylene, TPB, and TPB's degradation products were investigated in rabbits, mice and rats. The studies revealed these products to possess a very low toxicity.", "contents": "Toxicological studies of photosensitizer agents and photodegradable polyolefins. The authors report the results of a series of toxicological tests conducted on plastic materials (polyethylene) activated with tetraphenylbutadiene (TPB) an additive recently proposed as a sensitizer capable of photodegrading plastic materials. The toxic effects of polyethylene, TPB, and TPB's degradation products were investigated in rabbits, mice and rats. The studies revealed these products to possess a very low toxicity."} {"id": "PMID:1278272", "title": "Behavioural repertory of cats without cerebral cortex from infancy.", "content": "Bilateral removal of the cerebral cortex was made in cats neonatally. Spontaneous and imposed behaviour was studied while they were growing up and after they had become adult. Special emphasis was put on the utilization of visual cues and on learning. The cats ate, drank and groomed themselves adequately. Adequate maternal and female sexual behaviour was observed. They utilized the visual and haptic senses with respect to external space. Two cats were trained to perform visual discrimination if a T-maze. The adequacy of the behaviour of these cats is compared to that of animals with similar lesions made at maturity.", "contents": "Behavioural repertory of cats without cerebral cortex from infancy. Bilateral removal of the cerebral cortex was made in cats neonatally. Spontaneous and imposed behaviour was studied while they were growing up and after they had become adult. Special emphasis was put on the utilization of visual cues and on learning. The cats ate, drank and groomed themselves adequately. Adequate maternal and female sexual behaviour was observed. They utilized the visual and haptic senses with respect to external space. Two cats were trained to perform visual discrimination if a T-maze. The adequacy of the behaviour of these cats is compared to that of animals with similar lesions made at maturity."} {"id": "PMID:1278273", "title": "Early versus late visual cortex lesions: effects on receptive fields in cat superior colliculus.", "content": "Cats that sustain lesions of the visual cortex early in life appear to perform certain visual discrimination tasks better than those operated as adults. This study sought to determine whether this recovery is visual capacities was accompanied by reorganization of single cell responses at the level of the superior colliculus. Areas 17 and 18 were ablated in adult cats and in kittens at various times during the neonatal period. Responses of units in superior colliculus ipsilateral to the lesion were recorded following a prolonged recovery period. Following cortical lesions, collicular units rarely exhibited direction selectivity, binocularity was reduced in the majority of animals, and the ocular dominance distribution was biased toward the contralateral eye. The reduction of direction selectivity and binocularity were unrelated to the animal's age at operation.", "contents": "Early versus late visual cortex lesions: effects on receptive fields in cat superior colliculus. Cats that sustain lesions of the visual cortex early in life appear to perform certain visual discrimination tasks better than those operated as adults. This study sought to determine whether this recovery is visual capacities was accompanied by reorganization of single cell responses at the level of the superior colliculus. Areas 17 and 18 were ablated in adult cats and in kittens at various times during the neonatal period. Responses of units in superior colliculus ipsilateral to the lesion were recorded following a prolonged recovery period. Following cortical lesions, collicular units rarely exhibited direction selectivity, binocularity was reduced in the majority of animals, and the ocular dominance distribution was biased toward the contralateral eye. The reduction of direction selectivity and binocularity were unrelated to the animal's age at operation."} {"id": "PMID:1278274", "title": "Recovery of function in cat visual cortex following prolonged deprivation.", "content": "Evidence that there is a critical period during which response characteristics of neurons in visual cortex of the cat may be influenced has been provided in several studied, which suggest that the period of influence is restricted to the first few months of life. Using a somewhat different experimental procedure, we have obtained evidence that cortical units retain plasticity long after the end of this period has passed. In our procedure prolonged visual deprivation was followed by exposure in a normal visual environment. The animals were maintained throughout the first year of life either in total darkness or in an enclosure illuminated intermittently by a strobe light. Following the period of deprivation, electrophysiologic recordings were taken from some of these animals. The remaining cats were permitted 6-12 months in a normally-illuminated environment prior to recording. Cats of the same age reared from birth in a normally lit environment were also recorded. Cortical neurons in cats deprived of any normal visual experience rarely show orientation selective responses. In animals allowed subsequent normal visual experience about one-half of the units studied exhibited this property. This level of response specificity is intermediate between that of normally-reared and recently-deprived animals. While most cortical units in normally-reared cats exhibited direction selectivity, this property is rarely observed in the \"recovery\" cats. A number of unit types which are rarely observed in either normal or totally deprived animals were encountered in cats that had normal exposure following prolonged deprivation. A convergent strabismus was observed, in contrast with the divergent strabismus often shown by cats immediately following prolonged visual deprivation. This shows that ocular alignment as well as cortical unit properties can remain plastic in the adult.", "contents": "Recovery of function in cat visual cortex following prolonged deprivation. Evidence that there is a critical period during which response characteristics of neurons in visual cortex of the cat may be influenced has been provided in several studied, which suggest that the period of influence is restricted to the first few months of life. Using a somewhat different experimental procedure, we have obtained evidence that cortical units retain plasticity long after the end of this period has passed. In our procedure prolonged visual deprivation was followed by exposure in a normal visual environment. The animals were maintained throughout the first year of life either in total darkness or in an enclosure illuminated intermittently by a strobe light. Following the period of deprivation, electrophysiologic recordings were taken from some of these animals. The remaining cats were permitted 6-12 months in a normally-illuminated environment prior to recording. Cats of the same age reared from birth in a normally lit environment were also recorded. Cortical neurons in cats deprived of any normal visual experience rarely show orientation selective responses. In animals allowed subsequent normal visual experience about one-half of the units studied exhibited this property. This level of response specificity is intermediate between that of normally-reared and recently-deprived animals. While most cortical units in normally-reared cats exhibited direction selectivity, this property is rarely observed in the \"recovery\" cats. A number of unit types which are rarely observed in either normal or totally deprived animals were encountered in cats that had normal exposure following prolonged deprivation. A convergent strabismus was observed, in contrast with the divergent strabismus often shown by cats immediately following prolonged visual deprivation. This shows that ocular alignment as well as cortical unit properties can remain plastic in the adult."} {"id": "PMID:1278275", "title": "Effects of serial lesions of somatosensory cortex and further neodecortication on retention of a rough-smooth discrimination in rats.", "content": "Five groups of rats with bilateral lesions of the somatosensory cortex and one of animals sustained only sham operations were tested for retention of a rough-smooth discrimination. Two of the lesion groups had sequential unilateral ablations, in one case with interoperative testing, and three groups had one-stage bilateral lesions. The two groups of animals with serial lesions did not differ from each other or from sham operates in relearning the task. RAts with one-stage lesions and preoperative overtraining also performed well, but the other one-stage groups showed deficits relative to control and serial lesion groups. In the second experiment the sham operated rats from Experiment 1 experiences lesions anterior and posterior to the somatosensory zones. These lesions did not affect retention. Somatosensory cortex then was ablated in one operation and severe performance decrements were seen. Removal of additional neocortex in a sample of animals that had relearned the discrimination after one-stage somatosensory cortex lesions (Exp. 1) also affected retention. In contrast, retention was not impaired on some of the measures in those animals that originally had two-stage ablations. The findings from these two experiments show that some ablation effects can be circumvented with overtraining or serial lesion techniques. The data also indicate that non-somatosensory cortex may play a role in recovery after somatic cortex lesions, but that the substrates underlying recovery might not be the same after one-stage and two-stage ablations.", "contents": "Effects of serial lesions of somatosensory cortex and further neodecortication on retention of a rough-smooth discrimination in rats. Five groups of rats with bilateral lesions of the somatosensory cortex and one of animals sustained only sham operations were tested for retention of a rough-smooth discrimination. Two of the lesion groups had sequential unilateral ablations, in one case with interoperative testing, and three groups had one-stage bilateral lesions. The two groups of animals with serial lesions did not differ from each other or from sham operates in relearning the task. RAts with one-stage lesions and preoperative overtraining also performed well, but the other one-stage groups showed deficits relative to control and serial lesion groups. In the second experiment the sham operated rats from Experiment 1 experiences lesions anterior and posterior to the somatosensory zones. These lesions did not affect retention. Somatosensory cortex then was ablated in one operation and severe performance decrements were seen. Removal of additional neocortex in a sample of animals that had relearned the discrimination after one-stage somatosensory cortex lesions (Exp. 1) also affected retention. In contrast, retention was not impaired on some of the measures in those animals that originally had two-stage ablations. The findings from these two experiments show that some ablation effects can be circumvented with overtraining or serial lesion techniques. The data also indicate that non-somatosensory cortex may play a role in recovery after somatic cortex lesions, but that the substrates underlying recovery might not be the same after one-stage and two-stage ablations."} {"id": "PMID:1278290", "title": "Isolation of sodium-complexing polypeptides from mammalian blood and cardiac muscle.", "content": "Two distinct polypeptides have been isolated from rat heart and ox blood. They are both found to be effective in forming complexes with sodium ions, and it is suggested that they may have a function in stabilizing sodium ion activity.", "contents": "Isolation of sodium-complexing polypeptides from mammalian blood and cardiac muscle. Two distinct polypeptides have been isolated from rat heart and ox blood. They are both found to be effective in forming complexes with sodium ions, and it is suggested that they may have a function in stabilizing sodium ion activity."} {"id": "PMID:1278291", "title": "Is there a recycling of hydroxyproline?", "content": "Rats can produce glycine from hydroxyproline and vice versa. After the injection, hydroxyproline is rapidly converted into glycine and then incorporated into collagen. Later the labelled amino acids in collagen are hydroxyproline, proline, serine, threonine, alanine, and glutamic acid. We suppose that all these labelled amino acids come from glycine.", "contents": "Is there a recycling of hydroxyproline? Rats can produce glycine from hydroxyproline and vice versa. After the injection, hydroxyproline is rapidly converted into glycine and then incorporated into collagen. Later the labelled amino acids in collagen are hydroxyproline, proline, serine, threonine, alanine, and glutamic acid. We suppose that all these labelled amino acids come from glycine."} {"id": "PMID:1278292", "title": "Zeitgeber induced modulation of activity patterns in nocturnal mammals (Chiroptera).", "content": "Changing the L:D intensity ratio of a synchronizing dark regime leads to characteristic modulations of the activity pattern of Chiroptera species. These modulations fit the predictions of WEVER'S oscillator model.", "contents": "Zeitgeber induced modulation of activity patterns in nocturnal mammals (Chiroptera). Changing the L:D intensity ratio of a synchronizing dark regime leads to characteristic modulations of the activity pattern of Chiroptera species. These modulations fit the predictions of WEVER'S oscillator model."} {"id": "PMID:1278293", "title": "The effect of continuous exposure to low frequency electric fields on three generations of mice: a pilot study.", "content": "Mice were allowed to mate, gestate, deliver and rear their offspring for 3 successive generations while being continuously exposed to 60 Hz electric fields. Mice exposed to vertical electric fields exhibited decreased body weights at 35 days postpartum and increased mortality rates for 3 successive generations. Mice exposed to horizontal electric fields exhibited decreased body weights for 2 successive generations.", "contents": "The effect of continuous exposure to low frequency electric fields on three generations of mice: a pilot study. Mice were allowed to mate, gestate, deliver and rear their offspring for 3 successive generations while being continuously exposed to 60 Hz electric fields. Mice exposed to vertical electric fields exhibited decreased body weights at 35 days postpartum and increased mortality rates for 3 successive generations. Mice exposed to horizontal electric fields exhibited decreased body weights for 2 successive generations."} {"id": "PMID:1278294", "title": "Comparison of the effects of illumination on the melanophores of intact and eyestalkless fiddler crabs, Uca pugilator, and inhibition of the primary response by cytochalasin B.", "content": "Approximately 100 times more illumination is required to produce pigment dispersion in the melanophores of eyestalkless fiddler crabs (Uca pugilator) than in the melanophores of intact crabs. The pigment in melanophores of isolated legs will normally disperse in response to irradiation, but this response is inhibited by cytochalasin B.", "contents": "Comparison of the effects of illumination on the melanophores of intact and eyestalkless fiddler crabs, Uca pugilator, and inhibition of the primary response by cytochalasin B. Approximately 100 times more illumination is required to produce pigment dispersion in the melanophores of eyestalkless fiddler crabs (Uca pugilator) than in the melanophores of intact crabs. The pigment in melanophores of isolated legs will normally disperse in response to irradiation, but this response is inhibited by cytochalasin B."} {"id": "PMID:1278295", "title": "The influence of cobalt on the endoplasmatic reticulum of the horse bean (vicia faba l.).", "content": "The exogeneous application of cobalt induces the differentiation of membrane complexes of the endoplasmic reticulum. After longer acting of cobalt these membranes are dilated and later destroyed. This fact can manifest itself also in some disturbances of the cell division.", "contents": "The influence of cobalt on the endoplasmatic reticulum of the horse bean (vicia faba l.). The exogeneous application of cobalt induces the differentiation of membrane complexes of the endoplasmic reticulum. After longer acting of cobalt these membranes are dilated and later destroyed. This fact can manifest itself also in some disturbances of the cell division."} {"id": "PMID:1278296", "title": "Degradation of phenylalanine in the presence of hydrogen peroxide.", "content": "UV-irradiation of phenylalanine by 253.7 nm light in the presence of hydrogen peroxide formed 5 ninhydrin reactive products and ammonia. Four of them were identified as aspartic acid, serine, alanine and lysine.", "contents": "Degradation of phenylalanine in the presence of hydrogen peroxide. UV-irradiation of phenylalanine by 253.7 nm light in the presence of hydrogen peroxide formed 5 ninhydrin reactive products and ammonia. Four of them were identified as aspartic acid, serine, alanine and lysine."} {"id": "PMID:1278297", "title": "Noise and \"pedagogic efficiency\" in school activities.", "content": "A group of 8 pupils born in 1962 and a group of 8 future teachers between 25 and 40 years of age, were submitted in 1975 to two types of tests in the presence of environment noises at various levels (45 to 75 dBa), in order to assess the influence of this nuisance on the pedagogic efficiency. The results show a nocivity threshold for the pupils at around 55 dBA and for the teachers at aroung 65 dBA. Furthermore, backward pupils suffer more in this context from the interference of noise than the advanced ones.", "contents": "Noise and \"pedagogic efficiency\" in school activities. A group of 8 pupils born in 1962 and a group of 8 future teachers between 25 and 40 years of age, were submitted in 1975 to two types of tests in the presence of environment noises at various levels (45 to 75 dBa), in order to assess the influence of this nuisance on the pedagogic efficiency. The results show a nocivity threshold for the pupils at around 55 dBA and for the teachers at aroung 65 dBA. Furthermore, backward pupils suffer more in this context from the interference of noise than the advanced ones."} {"id": "PMID:1278298", "title": "Effect of ascorbic acid on pigmentation of toad (Bufo melanostictus).", "content": "Administration of ascorbic acid in toad during breeding season results an increase in melanin pigments in skin, liver and vocal sac.", "contents": "Effect of ascorbic acid on pigmentation of toad (Bufo melanostictus). Administration of ascorbic acid in toad during breeding season results an increase in melanin pigments in skin, liver and vocal sac."} {"id": "PMID:1278299", "title": "Locomotory energetics in a marsupial (Antechinomys spenceri) and a rodent (Notomys alexis).", "content": "Steady state oxygen consumption was compared in a rodent Notomys alexis and a marsupial Antechinomys spenceri. The marsupial was found to diverge from predicted eutherian energic patterns. N. alexis appears to use energy storage as a significant part of the step cycle before becoming bipedal. Aerobic scope and heat storage during running are similar in both species.", "contents": "Locomotory energetics in a marsupial (Antechinomys spenceri) and a rodent (Notomys alexis). Steady state oxygen consumption was compared in a rodent Notomys alexis and a marsupial Antechinomys spenceri. The marsupial was found to diverge from predicted eutherian energic patterns. N. alexis appears to use energy storage as a significant part of the step cycle before becoming bipedal. Aerobic scope and heat storage during running are similar in both species."} {"id": "PMID:1278300", "title": "Slow current changes underlying square shaped potential waves in warmed Aplysia neurones.", "content": "On warming, the regularly firing L11 neurone of Aplysia turns into a bursting-type neurone. The bursts of spikes are produced by slow square waves which can also be obtained at room temperature by adding TTX or Co++. Experiments with slow ramp voltage clamp show that warming induces a negative slope (or negative resistance) on the current-voltage characteristic and very slow current variations (r = 10 to 50 sec) in response to potential changes. The square waves are explained by these two phenomena.", "contents": "Slow current changes underlying square shaped potential waves in warmed Aplysia neurones. On warming, the regularly firing L11 neurone of Aplysia turns into a bursting-type neurone. The bursts of spikes are produced by slow square waves which can also be obtained at room temperature by adding TTX or Co++. Experiments with slow ramp voltage clamp show that warming induces a negative slope (or negative resistance) on the current-voltage characteristic and very slow current variations (r = 10 to 50 sec) in response to potential changes. The square waves are explained by these two phenomena."} {"id": "PMID:1278301", "title": "Neural serotonin receptors in active and hibernating helicid snails (Helix lucorum).", "content": "In hibernating snails Helix lucorum, the effect of 5-HT on neurons of an identified group is mainly hyperpolarization associated with a conzation conductance increase, while, inactive snails, the effect is de polarization decrease of the membrane conductance.", "contents": "Neural serotonin receptors in active and hibernating helicid snails (Helix lucorum). In hibernating snails Helix lucorum, the effect of 5-HT on neurons of an identified group is mainly hyperpolarization associated with a conzation conductance increase, while, inactive snails, the effect is de polarization decrease of the membrane conductance."} {"id": "PMID:1278302", "title": "A simple approach to the toad's (Bufo melanostictus) nerve muscle preparation.", "content": "A simple and modified dorsal approach method has been made in the toad's (Bufo melanostictus) sciatic gastrocnemius nerve-muscle preparation. This method incurs less blood loss, time consumption, nerve damage and visceral spoil compared to conventional ventral approach method.", "contents": "A simple approach to the toad's (Bufo melanostictus) nerve muscle preparation. A simple and modified dorsal approach method has been made in the toad's (Bufo melanostictus) sciatic gastrocnemius nerve-muscle preparation. This method incurs less blood loss, time consumption, nerve damage and visceral spoil compared to conventional ventral approach method."} {"id": "PMID:1278303", "title": "Gibberellin and nucleic acid metabolism during Zea mays fertilization.", "content": "Either by direct GA supply or by release of glycosidic bound GA, pollination causes partial opening of double-stranded DNA in somatic maize kernel tissues, as evidenced by increased Tm profiles. This phenomenon is associated with enhanced RNA and prtein production.", "contents": "Gibberellin and nucleic acid metabolism during Zea mays fertilization. Either by direct GA supply or by release of glycosidic bound GA, pollination causes partial opening of double-stranded DNA in somatic maize kernel tissues, as evidenced by increased Tm profiles. This phenomenon is associated with enhanced RNA and prtein production."} {"id": "PMID:1278304", "title": "Effects of deneravation and decentralization upon taste buds.", "content": "Denervation of vallate papillae results in failure of tactile and gustatory reception at a time when impulse conduction in the distal stump of the glossopharyngeal nerve is still unimpaired; delay of receptor deficit depends on axon length between receptor and axotomy sites; taste buds disappear by 10 days. Decentralization, through intracranial rhizotomy, does not modify lingual receptors structure or function.", "contents": "Effects of deneravation and decentralization upon taste buds. Denervation of vallate papillae results in failure of tactile and gustatory reception at a time when impulse conduction in the distal stump of the glossopharyngeal nerve is still unimpaired; delay of receptor deficit depends on axon length between receptor and axotomy sites; taste buds disappear by 10 days. Decentralization, through intracranial rhizotomy, does not modify lingual receptors structure or function."} {"id": "PMID:1278305", "title": "Is beta-(4-chlorophenyl)-GABA a specific antagonist of substance P on cerebral cortical neurons?", "content": "Beta-(4-chlorophenyl)-GABA (Baclofen, Lioresal) antagonized the excitant actions of acetylcholine and substance P to comparable extents. L-glutamate-induced excitation was affected to a lesser extent. These findings do not support the suggestion that beta-(4-chlorophenyl)-GABA is a specific substance P antagonist.", "contents": "Is beta-(4-chlorophenyl)-GABA a specific antagonist of substance P on cerebral cortical neurons? Beta-(4-chlorophenyl)-GABA (Baclofen, Lioresal) antagonized the excitant actions of acetylcholine and substance P to comparable extents. L-glutamate-induced excitation was affected to a lesser extent. These findings do not support the suggestion that beta-(4-chlorophenyl)-GABA is a specific substance P antagonist."} {"id": "PMID:1278306", "title": "A new wave (2nd c-wave) on corneoretinal potential.", "content": "The 2nd c-wave is a new wave of corneoretinal potential which is an on-response with a long latency (65-98 sec), and appears following the end of the c-wave of ERG. It suggested that the 2nd c-wave is based on the tail of the late receptor potential of the retina.", "contents": "A new wave (2nd c-wave) on corneoretinal potential. The 2nd c-wave is a new wave of corneoretinal potential which is an on-response with a long latency (65-98 sec), and appears following the end of the c-wave of ERG. It suggested that the 2nd c-wave is based on the tail of the late receptor potential of the retina."} {"id": "PMID:1278307", "title": "Interaction between two identified cells in the visceral ganglion of the snail, Helix pomatia.", "content": "An interneurone, making excitatory synaptic connections with a second neurone has been identified in the brain of Helix pomatia. The results suggest that the connection is monosynaptic.", "contents": "Interaction between two identified cells in the visceral ganglion of the snail, Helix pomatia. An interneurone, making excitatory synaptic connections with a second neurone has been identified in the brain of Helix pomatia. The results suggest that the connection is monosynaptic."} {"id": "PMID:1278308", "title": "Ultrastructural changes in the dorsal root ganglia evoked by thalidomide in rabbits.", "content": "Administration of the teratogenic drug thalidomide to pregnant does produces ultrastructural changes in foetal ganglion cells, Schwann cells and axons in the posterior root ganglia corresponding to forelimb segments deformed by the orug. Ultrastructural changes in ganglia appear on the 13th day of gestation, i.e., preceding the appearance of limb malformation.", "contents": "Ultrastructural changes in the dorsal root ganglia evoked by thalidomide in rabbits. Administration of the teratogenic drug thalidomide to pregnant does produces ultrastructural changes in foetal ganglion cells, Schwann cells and axons in the posterior root ganglia corresponding to forelimb segments deformed by the orug. Ultrastructural changes in ganglia appear on the 13th day of gestation, i.e., preceding the appearance of limb malformation."} {"id": "PMID:1278309", "title": "Antischistosomal and some toxicological properties of a nitrodiphenylaminoisothiocyanate (C 9333-Go/CGP 4540).", "content": "A procedure to enhance the schistosomicidal effectiveness in vivo of an isothiocyanate derivative and some of its antischistosomal properties are reported. Determinations of the effects of this compound on tissue thiol levels and on highly sensitivity bacterial tester strains have indicated that its mutagenic potential is of a low order and that the latter is decreased further after reduction of the host's intestinal bacterial flora.", "contents": "Antischistosomal and some toxicological properties of a nitrodiphenylaminoisothiocyanate (C 9333-Go/CGP 4540). A procedure to enhance the schistosomicidal effectiveness in vivo of an isothiocyanate derivative and some of its antischistosomal properties are reported. Determinations of the effects of this compound on tissue thiol levels and on highly sensitivity bacterial tester strains have indicated that its mutagenic potential is of a low order and that the latter is decreased further after reduction of the host's intestinal bacterial flora."} {"id": "PMID:1278310", "title": "Beta-blockade of morphine-induced hyperlactacidemia in rabbits.", "content": "In morphinized rabbits blood lactate levels are elevated. Hyperlactacidemia persists after cessation of morphine injections. This morphine-induced lactate accumulation is completely abolished by simultaneous propranolol treatment. Phentolamine does not modify the action of morphine.", "contents": "Beta-blockade of morphine-induced hyperlactacidemia in rabbits. In morphinized rabbits blood lactate levels are elevated. Hyperlactacidemia persists after cessation of morphine injections. This morphine-induced lactate accumulation is completely abolished by simultaneous propranolol treatment. Phentolamine does not modify the action of morphine."} {"id": "PMID:1278311", "title": "Frescon: neurophysiological action of a molluscicide.", "content": "The molluscidice N-trityl morpholine (Frescon) has an unusual effect on the central nervous system of a freshwater snail. Nerve impulses become grouped into spontaneous \"bursts\", with many cells firing synchronously. This may result from interference with inhibitory processes.", "contents": "Frescon: neurophysiological action of a molluscicide. The molluscidice N-trityl morpholine (Frescon) has an unusual effect on the central nervous system of a freshwater snail. Nerve impulses become grouped into spontaneous \"bursts\", with many cells firing synchronously. This may result from interference with inhibitory processes."} {"id": "PMID:1278312", "title": "Drug interactions in intestinal absorption of 3H-digitoxin in rats.", "content": "The absorption of 3H-digitoxin from perfused rat small intestine was inhibited by probenecid (1.0 x 10-2 M), ethacrynic acid (0.5 x 10-3 M), and mersalyl (8.0 x 10-3 M) indicating that digitoxin absorption is at least partly an active process.", "contents": "Drug interactions in intestinal absorption of 3H-digitoxin in rats. The absorption of 3H-digitoxin from perfused rat small intestine was inhibited by probenecid (1.0 x 10-2 M), ethacrynic acid (0.5 x 10-3 M), and mersalyl (8.0 x 10-3 M) indicating that digitoxin absorption is at least partly an active process."} {"id": "PMID:1278313", "title": "The biliary excretion of [3H] lysergic acid diethylamide in Wistar and Gunn rats.", "content": "The biliary excretion of [3H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.", "contents": "The biliary excretion of [3H] lysergic acid diethylamide in Wistar and Gunn rats. The biliary excretion of [3H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides."} {"id": "PMID:1278314", "title": "Differential effects of ethanol on prostaglandin responses of arterial and venous smooth muscles.", "content": "The present results, using isolated rat aortic strips and portal vein segments, demonstrate that ethanol, depending upon concentration, can either enhance or attenuate the contractile actions of PGF2alpha on at least 2 different types of vascular smooth muscle. At the very least, the present findings question that the use of ethanol as a solvent when investigating the contractile actions of PG molecules on smooth muscles.", "contents": "Differential effects of ethanol on prostaglandin responses of arterial and venous smooth muscles. The present results, using isolated rat aortic strips and portal vein segments, demonstrate that ethanol, depending upon concentration, can either enhance or attenuate the contractile actions of PGF2alpha on at least 2 different types of vascular smooth muscle. At the very least, the present findings question that the use of ethanol as a solvent when investigating the contractile actions of PG molecules on smooth muscles."} {"id": "PMID:1278315", "title": "Phenobarbital and SKF-525A on vinblastine and vincristine toxicity in mice.", "content": "The effect of SKF-525A and phenobarbital on the LD50 values of vinblastine and vincristine suggests that the toxicity of these agents in mice does not arise from a toxic metabolite.", "contents": "Phenobarbital and SKF-525A on vinblastine and vincristine toxicity in mice. The effect of SKF-525A and phenobarbital on the LD50 values of vinblastine and vincristine suggests that the toxicity of these agents in mice does not arise from a toxic metabolite."} {"id": "PMID:1278316", "title": "Elevation of serum xanthine oxidase following halothane anesthesia in the rat.", "content": "Halothan anesthesia was found to be hapatotoxic in the rat, as demonstrated by a significant elevation of serum xanthine oxidase (SXO) level. SXO appeared to be more sensitive marker of liver damage than serum glutamic oxalacetic transaminase. SXO was found to be elevated also following exposure to relative hypoxia.", "contents": "Elevation of serum xanthine oxidase following halothane anesthesia in the rat. Halothan anesthesia was found to be hapatotoxic in the rat, as demonstrated by a significant elevation of serum xanthine oxidase (SXO) level. SXO appeared to be more sensitive marker of liver damage than serum glutamic oxalacetic transaminase. SXO was found to be elevated also following exposure to relative hypoxia."} {"id": "PMID:1278317", "title": "Formation of lipoperoxide in the retina of rabbit exposed to high concentration of oxygen.", "content": "When rabbit was exposed to high concentrations of oxygen, lipoperoxide in the retina was increased at 12 h of the exposure, after which period amplitude of electro-retinogram decreased. The degeneration was observed in the visual cell layer of the retina of the exposed animal. The exposure increased lipoperoxide in isolated retina. These data show the intervention of lipoperoxide in retinal degeneration by exposure to high concentration of oxygen.", "contents": "Formation of lipoperoxide in the retina of rabbit exposed to high concentration of oxygen. When rabbit was exposed to high concentrations of oxygen, lipoperoxide in the retina was increased at 12 h of the exposure, after which period amplitude of electro-retinogram decreased. The degeneration was observed in the visual cell layer of the retina of the exposed animal. The exposure increased lipoperoxide in isolated retina. These data show the intervention of lipoperoxide in retinal degeneration by exposure to high concentration of oxygen."} {"id": "PMID:1278318", "title": "Laminar Acetylcholinesterase localization in the optic tectum of five seawater teleosts.", "content": "The histochemical localization of acetylcholinesterase in the optic tectum of seawater teleosts shows a characteristic laminar distribution which parallels the histological structure of the nervous centre. Significant differences have been observed between Gobius and the other 4 species of teleosts examined. It seems likely that cholinergic mechanisms play an important role in the function of teleost optic tectum.", "contents": "Laminar Acetylcholinesterase localization in the optic tectum of five seawater teleosts. The histochemical localization of acetylcholinesterase in the optic tectum of seawater teleosts shows a characteristic laminar distribution which parallels the histological structure of the nervous centre. Significant differences have been observed between Gobius and the other 4 species of teleosts examined. It seems likely that cholinergic mechanisms play an important role in the function of teleost optic tectum."} {"id": "PMID:1278319", "title": "Lipid and phospholipid content and fatty acid composition of the chick lung during embryonic development.", "content": "The evolution of total phospholipid, phosphatidylcholine and phosphatidylethanolamine content of chick lung during embryonic development is in good agreement with morphological data. Saturated fatty acids are predominant. A sex-linked difference is observed in the evolution of phosphatidylcholine.", "contents": "Lipid and phospholipid content and fatty acid composition of the chick lung during embryonic development. The evolution of total phospholipid, phosphatidylcholine and phosphatidylethanolamine content of chick lung during embryonic development is in good agreement with morphological data. Saturated fatty acids are predominant. A sex-linked difference is observed in the evolution of phosphatidylcholine."} {"id": "PMID:1278320", "title": "Abnormal mitochondria in retinoblastoma.", "content": "In examination of six retinoblastoma tumor specimens, bizzare mitochondria were often found. Some are irregular forms with focal expansion and constrictions. Occasionally, a portion of the mitochondria forms rings. Branching mitochondria are also seen. Other striking features of the mitochondria from tumor cells are the alternation of cristae. Dense bodies are also occasionally observed within the mitochondria. Morphological modifications of the mitochondria may be as results of pathological conditions of the tumor cells.", "contents": "Abnormal mitochondria in retinoblastoma. In examination of six retinoblastoma tumor specimens, bizzare mitochondria were often found. Some are irregular forms with focal expansion and constrictions. Occasionally, a portion of the mitochondria forms rings. Branching mitochondria are also seen. Other striking features of the mitochondria from tumor cells are the alternation of cristae. Dense bodies are also occasionally observed within the mitochondria. Morphological modifications of the mitochondria may be as results of pathological conditions of the tumor cells."} {"id": "PMID:1278321", "title": "Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum.", "content": "Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum.", "contents": "Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum. Pentalaminar specialized membrane junctions - tight junctions - are described in the granular layer of the pigeon cerebellum. The presence of these axo-dendritique and dendrosomatic contacts suggest the existence of electrotonic coupling in the pigeon cerebellum."} {"id": "PMID:1278322", "title": "Alpha-tocopherol: its inhibition on human platelet aggregation.", "content": "Alpha-tocopherol inhibits human platelet aggregation induced by arachidonate sodium, collagen, epinephrine, adenosine diphosphate or thrombin - arachidonate sodium being the most susceptible. The second phase of the biphasic platelet aggregation induced by epinephrine or adenosine diphosphate is preferentially inhibited.", "contents": "Alpha-tocopherol: its inhibition on human platelet aggregation. Alpha-tocopherol inhibits human platelet aggregation induced by arachidonate sodium, collagen, epinephrine, adenosine diphosphate or thrombin - arachidonate sodium being the most susceptible. The second phase of the biphasic platelet aggregation induced by epinephrine or adenosine diphosphate is preferentially inhibited."} {"id": "PMID:1278323", "title": "Effect of dipyridamole on human platelet phospholipids.", "content": "The effect of dipyridamole on platelet phospholipids has been studied. After the platelet incubation with dipyridamole, a 38% reduction in the concentration of the sphingomyelin and a 21% increase in phosphatidyl choline were produced.", "contents": "Effect of dipyridamole on human platelet phospholipids. The effect of dipyridamole on platelet phospholipids has been studied. After the platelet incubation with dipyridamole, a 38% reduction in the concentration of the sphingomyelin and a 21% increase in phosphatidyl choline were produced."} {"id": "PMID:1278324", "title": "Time function of corticosteroid levels in the blood plasma of rats under the influence of 222Rn inhalation.", "content": "The time function of cortocosteroid level in plasma of rats under two different 222Rn concentrations was investigated. Both curves show a maximum after 8h. Whereas the higher activity of 222Rn produces a second maximum after 5 days, the lower activity reaches its second maximum not before 9 days. From both time functions, a two-step mechanism in the intracellular control can be concluded.", "contents": "Time function of corticosteroid levels in the blood plasma of rats under the influence of 222Rn inhalation. The time function of cortocosteroid level in plasma of rats under two different 222Rn concentrations was investigated. Both curves show a maximum after 8h. Whereas the higher activity of 222Rn produces a second maximum after 5 days, the lower activity reaches its second maximum not before 9 days. From both time functions, a two-step mechanism in the intracellular control can be concluded."} {"id": "PMID:1278325", "title": "Histamine as an extremely potent releaser of vasopressin in the rat.", "content": "Intraperitoneal and intraventricualr injection of histamine induces a very fast and high elevation of vasopressin in rat plasma as determined by radioimmunoassay. The effects are dose and time related. The intraventricular injection is more effective with regard to time and dose than the intraperitoneal injection.", "contents": "Histamine as an extremely potent releaser of vasopressin in the rat. Intraperitoneal and intraventricualr injection of histamine induces a very fast and high elevation of vasopressin in rat plasma as determined by radioimmunoassay. The effects are dose and time related. The intraventricular injection is more effective with regard to time and dose than the intraperitoneal injection."} {"id": "PMID:1278326", "title": "Successive clutches induced by surgical excision of post-ovulatory oocytes in the lizard Cnemidophorus uniparens.", "content": "19 animals had eggs excised from the oviducts soon after ovulation. Number of clutches was nearly tripled in excised animals as compared to controls. An influence of eggs in the oviduct on number of clutches is suggested and may indicate a neuronal link between oviduct and hypothalamus.", "contents": "Successive clutches induced by surgical excision of post-ovulatory oocytes in the lizard Cnemidophorus uniparens. 19 animals had eggs excised from the oviducts soon after ovulation. Number of clutches was nearly tripled in excised animals as compared to controls. An influence of eggs in the oviduct on number of clutches is suggested and may indicate a neuronal link between oviduct and hypothalamus."} {"id": "PMID:1278327", "title": "Precocious puberty in rats induced by hypothalamic lesions: a comparison of platinum and stainless steel electrodes.", "content": "Precocious sexual maturation was induced in immature female rats by 2 types of unilateral hypothalamic lesions. Stainless steel electrodes produced smaller tissue defects but proved more efficient than platinum electrodes.", "contents": "Precocious puberty in rats induced by hypothalamic lesions: a comparison of platinum and stainless steel electrodes. Precocious sexual maturation was induced in immature female rats by 2 types of unilateral hypothalamic lesions. Stainless steel electrodes produced smaller tissue defects but proved more efficient than platinum electrodes."} {"id": "PMID:1278328", "title": "A simple system for mechanical and electrical recordings from frog nerve-muscle preparation.", "content": "A device is described which can be used for simultaneous measurement of the muscle action potential and the contraction of the frog gastrocnemius nerve-muscle preparation. The apparatus is characterized by ease of construction, good accuracy and reliability.", "contents": "A simple system for mechanical and electrical recordings from frog nerve-muscle preparation. A device is described which can be used for simultaneous measurement of the muscle action potential and the contraction of the frog gastrocnemius nerve-muscle preparation. The apparatus is characterized by ease of construction, good accuracy and reliability."} {"id": "PMID:1278329", "title": "Brain chopping: a new method for the rapid removal of newborn rat brain.", "content": "A new multi-bladed air-driven guillotine is described. This device removes newborn rat heads and slices them into several thin wafers, which facilitates freezing and permits easy regional dissection.", "contents": "Brain chopping: a new method for the rapid removal of newborn rat brain. A new multi-bladed air-driven guillotine is described. This device removes newborn rat heads and slices them into several thin wafers, which facilitates freezing and permits easy regional dissection."} {"id": "PMID:1278330", "title": "Technical note about simultaneous recording of oxygen partial pressure and neuronal activity in cat cortex.", "content": "A method is described for simultaneous measurements of pO2 and action potentials with microelectrodes using prefabricated gold wires. The construction and measuring with such gold electrodes is easier than with traditionally used platinum electrodes. Single electrodes recording is done with a specially adapted electronic circuit, allowing the separation of both signals (pO2 and action potentials. A measurement in cat brain illustrates this procedure.", "contents": "Technical note about simultaneous recording of oxygen partial pressure and neuronal activity in cat cortex. A method is described for simultaneous measurements of pO2 and action potentials with microelectrodes using prefabricated gold wires. The construction and measuring with such gold electrodes is easier than with traditionally used platinum electrodes. Single electrodes recording is done with a specially adapted electronic circuit, allowing the separation of both signals (pO2 and action potentials. A measurement in cat brain illustrates this procedure."} {"id": "PMID:1278331", "title": "Holding plastic-embedded specimens for sectioning in a rotary microtome.", "content": "Three methods are evaluated for holding capsules of plastic-embedded tissue for rotary microtomy. Use of a V-block is rapid but deforms the capsule. Gluing the capsule to a supporting block is useful for reorientation of the capsule but otherwise time consuming. adapter is easy to use, does not deform the tissue, and is the preferred method for routine microtomy.", "contents": "Holding plastic-embedded specimens for sectioning in a rotary microtome. Three methods are evaluated for holding capsules of plastic-embedded tissue for rotary microtomy. Use of a V-block is rapid but deforms the capsule. Gluing the capsule to a supporting block is useful for reorientation of the capsule but otherwise time consuming. adapter is easy to use, does not deform the tissue, and is the preferred method for routine microtomy."} {"id": "PMID:1278332", "title": "A new technique for dissociation of hair follicles into single cells.", "content": "A method is described for the complete dissociation of mouse hair follicles into a suspension of single cells suitable for cell culture. Dermal tissue containing hair follicles is digested sequentially with trypsin and chondroitinase ABC under mild conditions.", "contents": "A new technique for dissociation of hair follicles into single cells. A method is described for the complete dissociation of mouse hair follicles into a suspension of single cells suitable for cell culture. Dermal tissue containing hair follicles is digested sequentially with trypsin and chondroitinase ABC under mild conditions."} {"id": "PMID:1278345", "title": "[Pharmacological properties of the methylamide of N-(4-antipyril)-oxaminic acid (oxapyrine)].", "content": "Comparative results of a pharmacological study on amidopyrine and a new original drug--N-(4-antipyril)-oxaminic methylamide are reported. Investigations conducted on animals showed the anodyne action of amidopyrine to manifest itself in toxic doses. This drug has a direct depressing effect on an isolated heart, a length of the intestine and the uretus of test animals. When employed in experimental conditions N-(4-antipyril) oxaminic methylamide displayed a much greater analgesic action that did amidipyrine. The drug has low toxicity both with its single and systemic introduction for a period of 60 days and it produces no inhibitory effect on isolated smooth muscle organs. It is concluded that the advantages of the newly synthetized agent come as a result of purposefully made structural changes in the formula, viz by introduction of a hydrazine group and of an oxaminic radical in the side chain.", "contents": "[Pharmacological properties of the methylamide of N-(4-antipyril)-oxaminic acid (oxapyrine)]. Comparative results of a pharmacological study on amidopyrine and a new original drug--N-(4-antipyril)-oxaminic methylamide are reported. Investigations conducted on animals showed the anodyne action of amidopyrine to manifest itself in toxic doses. This drug has a direct depressing effect on an isolated heart, a length of the intestine and the uretus of test animals. When employed in experimental conditions N-(4-antipyril) oxaminic methylamide displayed a much greater analgesic action that did amidipyrine. The drug has low toxicity both with its single and systemic introduction for a period of 60 days and it produces no inhibitory effect on isolated smooth muscle organs. It is concluded that the advantages of the newly synthetized agent come as a result of purposefully made structural changes in the formula, viz by introduction of a hydrazine group and of an oxaminic radical in the side chain."} {"id": "PMID:1278346", "title": "[Toxicity of etmozine, a new antiarrhythmic agent].", "content": "In tests set up on albino rats, guinea pigs and dogs chronic toxicity of aetmozine--a new antiarrhythmic drug used enterally in a dose of 35 mg/kg for periods of 1.3 and 6 months was studied. With different follow-up periods aetmozine was found not to lower the weight gain of the animals, nor to have any adverse effect on the blood and act as a local irritant. Histopathological changes occurring in the internal organs of the animals are of a reversible nature. Single oral administrations of the drug in a dose of 300 mg/kg at different terms of pregnancy did not produce any embryotoxic or teratogenous effects in rats.", "contents": "[Toxicity of etmozine, a new antiarrhythmic agent]. In tests set up on albino rats, guinea pigs and dogs chronic toxicity of aetmozine--a new antiarrhythmic drug used enterally in a dose of 35 mg/kg for periods of 1.3 and 6 months was studied. With different follow-up periods aetmozine was found not to lower the weight gain of the animals, nor to have any adverse effect on the blood and act as a local irritant. Histopathological changes occurring in the internal organs of the animals are of a reversible nature. Single oral administrations of the drug in a dose of 300 mg/kg at different terms of pregnancy did not produce any embryotoxic or teratogenous effects in rats."} {"id": "PMID:1278347", "title": "[Cardiovascular effects of diazepam and chlordiazepoxide in experiments on non-narcotized animals].", "content": "Tests staged on non-anesthetized cats demonstrated that the symptoms of the inhibited behaviour of the animals following introduction of diazepam and chlordiazepoxide are attended by hypertension, tachycardia and an increased intensity of pressor vasomotor reflexes. Urethan and chlorasole lessened the intensity of the activating effect of the tranquilizers on the central component of the sympathetic nervous system tonicity.", "contents": "[Cardiovascular effects of diazepam and chlordiazepoxide in experiments on non-narcotized animals]. Tests staged on non-anesthetized cats demonstrated that the symptoms of the inhibited behaviour of the animals following introduction of diazepam and chlordiazepoxide are attended by hypertension, tachycardia and an increased intensity of pressor vasomotor reflexes. Urethan and chlorasole lessened the intensity of the activating effect of the tranquilizers on the central component of the sympathetic nervous system tonicity."} {"id": "PMID:1278348", "title": "[Effect of thyrocalcitonin on the recovery processes in adrenaline lesion of the myocardium].", "content": "Administration of thyrocalcitonine (TCT) in doses of 0.1 and 1 Un/kg for 14 days prevented the development of myocarditis in rats receiving epinephrine (3 mg/kg) for 4 days reduced the death rate among the animals, increased their body weight and normalized the electrolytes composition in the heart. Given in a dose of 10 Un/kg the drug produced a less pronounced positive effect on the study values in the animals with experimentally-produced epinephrine lesion of the heart. According to the authors this may be occasioned by an intensified secretion of the parathyroid hormone in response to a multiple introduction of large TCT doses to the animals.", "contents": "[Effect of thyrocalcitonin on the recovery processes in adrenaline lesion of the myocardium]. Administration of thyrocalcitonine (TCT) in doses of 0.1 and 1 Un/kg for 14 days prevented the development of myocarditis in rats receiving epinephrine (3 mg/kg) for 4 days reduced the death rate among the animals, increased their body weight and normalized the electrolytes composition in the heart. Given in a dose of 10 Un/kg the drug produced a less pronounced positive effect on the study values in the animals with experimentally-produced epinephrine lesion of the heart. According to the authors this may be occasioned by an intensified secretion of the parathyroid hormone in response to a multiple introduction of large TCT doses to the animals."} {"id": "PMID:1278349", "title": "[Effect of pyridinolcarbamate (parmidine) on some bradykinin effects].", "content": "The influence of pyridinolcarbamate (parmidine) on raising the tonicity of bronchial and intestinal muscles in guinea pigs, and also on the edema of the paw in rats, induced with bradykinin was studied. Parmidin displays a specific antibradykinin activity and mitigates the effects of bradykinin in all the objects under investigation, without exercising any influence on the spasmogenic action of histamine, serotonin and acetylcholine.", "contents": "[Effect of pyridinolcarbamate (parmidine) on some bradykinin effects]. The influence of pyridinolcarbamate (parmidine) on raising the tonicity of bronchial and intestinal muscles in guinea pigs, and also on the edema of the paw in rats, induced with bradykinin was studied. Parmidin displays a specific antibradykinin activity and mitigates the effects of bradykinin in all the objects under investigation, without exercising any influence on the spasmogenic action of histamine, serotonin and acetylcholine."} {"id": "PMID:1278350", "title": "[Action of some pyrazolone derivatives on thrombocyte aggregation].", "content": "The influence of four agents--pyrazolidinedione derivatives on the ADP-induced aggregation and activity of glycolytic enzymes--glyceraldehydrophosphate dehydrogenase and lactate dehydrogenase (GAPD, LDG) and of the anatomic oxidation enzyme--glucose-6-phosphate dehydrogenase (G-6-PD) was studied. The substances known by a conventional designation of MYaK-38, No-13 and No-2 are shown to display an antiaggregational action. Amidopyrine was found to depress the adhesive capacity of blood platelets, to activate GAPD and LDG and to lower the activity of G-6-PD.", "contents": "[Action of some pyrazolone derivatives on thrombocyte aggregation]. The influence of four agents--pyrazolidinedione derivatives on the ADP-induced aggregation and activity of glycolytic enzymes--glyceraldehydrophosphate dehydrogenase and lactate dehydrogenase (GAPD, LDG) and of the anatomic oxidation enzyme--glucose-6-phosphate dehydrogenase (G-6-PD) was studied. The substances known by a conventional designation of MYaK-38, No-13 and No-2 are shown to display an antiaggregational action. Amidopyrine was found to depress the adhesive capacity of blood platelets, to activate GAPD and LDG and to lower the activity of G-6-PD."} {"id": "PMID:1278351", "title": "[Antiviral inhibitor induction under the influence of some anti-inflammatory agents].", "content": "An investigation into the effect produced by a series of acyl-derivatives of pyrasolone and salicytates on the generation of antiviral inhibitors (AVI) to the RNA and DNA-carrying viruses in the tissue cultures and chick embryos ascertained the active AVI inhibitors to be derivatives of 4-amino- and 4-methylaminoantipyrine, acylated with higher fatty and substituted benzoic acids.", "contents": "[Antiviral inhibitor induction under the influence of some anti-inflammatory agents]. An investigation into the effect produced by a series of acyl-derivatives of pyrasolone and salicytates on the generation of antiviral inhibitors (AVI) to the RNA and DNA-carrying viruses in the tissue cultures and chick embryos ascertained the active AVI inhibitors to be derivatives of 4-amino- and 4-methylaminoantipyrine, acylated with higher fatty and substituted benzoic acids."} {"id": "PMID:1278353", "title": "[Effect of different doses of tetramethylthiuram disulfide on the enzyme-forming function of the small intestine].", "content": "The effect of tetramethylthiuramdisulphide on the activity of the small intestine mucosa in rats was studied. When administered in different doses the compound was found to bring about, in the main, a fall of the monoglyceride-lipase and dipeptidase and a rise of the invertase alkaline-phosphatase and amylolytic activity. A protracted introduction of the compound brings down the weight of the small intestine mucosa. One month after stoppage of the drug's administration in a dose of 1/50 DL50 practised for 6 months and 15 days following its single introduction in a dose of 1/3 DL50 the enzymatic and the weight of the intestinal mucosa returned back to normal.", "contents": "[Effect of different doses of tetramethylthiuram disulfide on the enzyme-forming function of the small intestine]. The effect of tetramethylthiuramdisulphide on the activity of the small intestine mucosa in rats was studied. When administered in different doses the compound was found to bring about, in the main, a fall of the monoglyceride-lipase and dipeptidase and a rise of the invertase alkaline-phosphatase and amylolytic activity. A protracted introduction of the compound brings down the weight of the small intestine mucosa. One month after stoppage of the drug's administration in a dose of 1/50 DL50 practised for 6 months and 15 days following its single introduction in a dose of 1/3 DL50 the enzymatic and the weight of the intestinal mucosa returned back to normal."} {"id": "PMID:1278354", "title": "[Effectiveness of sodium selenite in experimental liver dystrophy].", "content": "The effect of sodium selenite on the cholepoietic function of the liver in rats with acute dystrophy induced by carbon tetrachloride was studied. When used in doses of 1 and 10 gamma/100 g the drug was found to normalize the intensity of bile secretion, synthesis and secretion of bile acids and that of bilirubin, as well as excretion of cholesterol. This was attended by a rise of the cholate-cholesterol ratio.", "contents": "[Effectiveness of sodium selenite in experimental liver dystrophy]. The effect of sodium selenite on the cholepoietic function of the liver in rats with acute dystrophy induced by carbon tetrachloride was studied. When used in doses of 1 and 10 gamma/100 g the drug was found to normalize the intensity of bile secretion, synthesis and secretion of bile acids and that of bilirubin, as well as excretion of cholesterol. This was attended by a rise of the cholate-cholesterol ratio."} {"id": "PMID:1278355", "title": "[Is liver microsomal enzyme induction the cause of tolerance to barbiturates?].", "content": "In 12, 24 and 48 hours after a single injection of phenobarbital, barbital-sodium and pentabarbital-sodium in doses of 80 175 an 40 mg/kg respectively an increased synthesis of protein in the cell-free protein-synthetizing system and a rise in the level of cytochromes b5 and P-450 in the liver microsomes of female rats were noted. The maximal changes were registered following introduction of phenobarbital the inducing capacity of barbital-sodium and pentabarbital-sodium twice as low. With chronic introduction of the drugs the tolerance with respect to all of them develops at an equal rate, which excludes the dependence of this phenomenon upon the induction of microsomal metabolizing enzymes of the liver.", "contents": "[Is liver microsomal enzyme induction the cause of tolerance to barbiturates?]. In 12, 24 and 48 hours after a single injection of phenobarbital, barbital-sodium and pentabarbital-sodium in doses of 80 175 an 40 mg/kg respectively an increased synthesis of protein in the cell-free protein-synthetizing system and a rise in the level of cytochromes b5 and P-450 in the liver microsomes of female rats were noted. The maximal changes were registered following introduction of phenobarbital the inducing capacity of barbital-sodium and pentabarbital-sodium twice as low. With chronic introduction of the drugs the tolerance with respect to all of them develops at an equal rate, which excludes the dependence of this phenomenon upon the induction of microsomal metabolizing enzymes of the liver."} {"id": "PMID:1278356", "title": "[Effect of retabolil and thyrocalcitonin on mineral metabolism in the bones of rats following a fracture of the lower jaw].", "content": "In tests conducted with 65 male-rats of the Wistar line, aged 2-3 months subject to studies was the effect of retabolil (RB) and thyrocalcitonine (TCT) on the mineral metabolism in the osseous tissue following fracture of the lower jaw. The per cent of the Ca45 isotope incorporation in the injured and unaffected (contralateral) sections of the jaw and also in the thigh bones, lying far away from the site of the injury, was determined in dynamics. The agents RB and TCT, displaying different modes of action, produce a similarly oriented effect, viz. accelerated mineralization of the osseous tissue, which is evident from an increased incorporation of the Ca45 isotope in the fracture area during the first post-traumatic week, followed by declining incorporation on the 14-28th day.", "contents": "[Effect of retabolil and thyrocalcitonin on mineral metabolism in the bones of rats following a fracture of the lower jaw]. In tests conducted with 65 male-rats of the Wistar line, aged 2-3 months subject to studies was the effect of retabolil (RB) and thyrocalcitonine (TCT) on the mineral metabolism in the osseous tissue following fracture of the lower jaw. The per cent of the Ca45 isotope incorporation in the injured and unaffected (contralateral) sections of the jaw and also in the thigh bones, lying far away from the site of the injury, was determined in dynamics. The agents RB and TCT, displaying different modes of action, produce a similarly oriented effect, viz. accelerated mineralization of the osseous tissue, which is evident from an increased incorporation of the Ca45 isotope in the fracture area during the first post-traumatic week, followed by declining incorporation on the 14-28th day."} {"id": "PMID:1278360", "title": "Antiinflammatory activity of two phenylindandione derivatives.", "content": "2-5-Dibromo-2-(beta-naphtyl)indan-1,3-dione (43/63) and 4-bromo-2-phenylindan-1,3-dione (43/13) are two interesting members of a series of \"indandione\" derivatives which possess an antiinflammatory activity (in the following tests: carrageenin induced rat hind paw edema, cotton pellets granuloma and chronic adjuvant arthritis). The two drugs are devoided of anticoagulant activity and their antiinflammatory effect is not adrenalmediated.", "contents": "Antiinflammatory activity of two phenylindandione derivatives. 2-5-Dibromo-2-(beta-naphtyl)indan-1,3-dione (43/63) and 4-bromo-2-phenylindan-1,3-dione (43/13) are two interesting members of a series of \"indandione\" derivatives which possess an antiinflammatory activity (in the following tests: carrageenin induced rat hind paw edema, cotton pellets granuloma and chronic adjuvant arthritis). The two drugs are devoided of anticoagulant activity and their antiinflammatory effect is not adrenalmediated."} {"id": "PMID:1278357", "title": "[Allergenic action of armin].", "content": "The allergic effect of armine--ethyl paranitrophenyl ether of the ethylpohosphinic acid--was studied. Armine was injected subcutaneously in doses of 0.1, 0.01, 0.005 and 0.0005 mg/kg to guinea pigs 5-6 times at intervals of 2-3 days. The challenging introduction of armine in a dose equalling the sensitizing one produced an anaphylactic shock in a group of animals sensitized with single doses of 0.005 and 0.0005 mg/kg. The allergic nature of these reactions was also confirmed by a large number of positive results secondary to immunological tests preceding the challenging dose, viz. by degranulation of mast cells, agglomeration of leucocytes and passive skin anaphylaxis.", "contents": "[Allergenic action of armin]. The allergic effect of armine--ethyl paranitrophenyl ether of the ethylpohosphinic acid--was studied. Armine was injected subcutaneously in doses of 0.1, 0.01, 0.005 and 0.0005 mg/kg to guinea pigs 5-6 times at intervals of 2-3 days. The challenging introduction of armine in a dose equalling the sensitizing one produced an anaphylactic shock in a group of animals sensitized with single doses of 0.005 and 0.0005 mg/kg. The allergic nature of these reactions was also confirmed by a large number of positive results secondary to immunological tests preceding the challenging dose, viz. by degranulation of mast cells, agglomeration of leucocytes and passive skin anaphylaxis."} {"id": "PMID:1278361", "title": "[New chloro derivatives of benzothiopyrano indoles and quinolines].", "content": "Some chloro derivatives of the carcinogenic [1]benzothiopyrano[4,3-b] indoles and 6H[1] benzothiopyrano[4,3-b] quinolines have been synthesized from 7- and 8-chlorothiochroman-4-one. Mass spectral data of these compounds are comparated with those of benzothiopyranoindole. Biological tests for carcinogenic activity are in progress.", "contents": "[New chloro derivatives of benzothiopyrano indoles and quinolines]. Some chloro derivatives of the carcinogenic [1]benzothiopyrano[4,3-b] indoles and 6H[1] benzothiopyrano[4,3-b] quinolines have been synthesized from 7- and 8-chlorothiochroman-4-one. Mass spectral data of these compounds are comparated with those of benzothiopyranoindole. Biological tests for carcinogenic activity are in progress."} {"id": "PMID:1278358", "title": "[Comparative evaluation of the toxicity of potassium hydrocarbonate and potassium chloride].", "content": "The potassium hydrocarbonate and potassium chloride toxicity was compared in experiments on 113 albino rats. The death following introduction of maximal amounts of potassium chloride was noted to supervene earlier than it did in animals receiving equivalent doses of potassium hydrocarbonate. Simultaneous introduction of sodium hydrocarbonate lowered the toxicity of both potassium hydrocarbonate and chloride. Morphological investigations revealed that toxic doses of potassium hydrocarbonate bring about shifts in the carbohydrate and lipids metabolism. Some mechanisms behind the action produced potassium chloride and hydrocarbonate are discussed.", "contents": "[Comparative evaluation of the toxicity of potassium hydrocarbonate and potassium chloride]. The potassium hydrocarbonate and potassium chloride toxicity was compared in experiments on 113 albino rats. The death following introduction of maximal amounts of potassium chloride was noted to supervene earlier than it did in animals receiving equivalent doses of potassium hydrocarbonate. Simultaneous introduction of sodium hydrocarbonate lowered the toxicity of both potassium hydrocarbonate and chloride. Morphological investigations revealed that toxic doses of potassium hydrocarbonate bring about shifts in the carbohydrate and lipids metabolism. Some mechanisms behind the action produced potassium chloride and hydrocarbonate are discussed."} {"id": "PMID:1278362", "title": "Radiopaque contrast media. XXXV - Physical properties of iopronic acid, a new oral cholecystographic agent.", "content": "Some physical properties of iopronic acid a new oral cholecystographic agent are reported. Determined are U.V., I.R., N.M.R. and mass spectra, X-Ray powder diffraction melting point and DTA, solubility, acidity constant and partition coefficient.", "contents": "Radiopaque contrast media. XXXV - Physical properties of iopronic acid, a new oral cholecystographic agent. Some physical properties of iopronic acid a new oral cholecystographic agent are reported. Determined are U.V., I.R., N.M.R. and mass spectra, X-Ray powder diffraction melting point and DTA, solubility, acidity constant and partition coefficient."} {"id": "PMID:1278359", "title": "[Dynamics of some carbohydrate metabolic indices in the liver and the alcohol concentration in it depending on the time of day of its administration].", "content": "The liver glycogen and sugar levels in intact rats are shown to experience diuranal variations with a maximum at 3-9 and minimum at 15-21 hours. Intragastric administration of ethanol in a dose of 1.5 ml/100 g produced an abrupt fall of the glycogen content in the liver of rats in 3.12 and maximally after a lapse of 6 hours, this being followed by a drop in the amount of sugar in 12 hours. The decline in the level of metabolites at different periods of the day (3, 9, 15 and 21 hr) was dissimilar. The lethality among the animals and concentration of the alcohol in the liver 3 and 6 hours following the action of alcohol at the hours of the day under study correlated and were inversely proportional to the sugar and glycogen content of the same hours of the day.", "contents": "[Dynamics of some carbohydrate metabolic indices in the liver and the alcohol concentration in it depending on the time of day of its administration]. The liver glycogen and sugar levels in intact rats are shown to experience diuranal variations with a maximum at 3-9 and minimum at 15-21 hours. Intragastric administration of ethanol in a dose of 1.5 ml/100 g produced an abrupt fall of the glycogen content in the liver of rats in 3.12 and maximally after a lapse of 6 hours, this being followed by a drop in the amount of sugar in 12 hours. The decline in the level of metabolites at different periods of the day (3, 9, 15 and 21 hr) was dissimilar. The lethality among the animals and concentration of the alcohol in the liver 3 and 6 hours following the action of alcohol at the hours of the day under study correlated and were inversely proportional to the sugar and glycogen content of the same hours of the day."} {"id": "PMID:1278363", "title": "Synthesis of (+/-)-8,12-trans-delta5-en-cis-11-KETO-14,15-trans-en-16-R,S-hydroxyprostanoic acid methyl ester.", "content": "The synthesis of (+/-)-8,12-trans-delta5-en-cis-11-keto-14,15-trans-en-16-R,S-hydroxyprostanoic acid methyl ester (XIII) from 2-allyl-2-cyclopentenone (I) is described. The key products are the conjugate enone (IX) or the acetylenic secondary alcohol (X) derived from 2-propargyl-2-cyclopentenone (II).", "contents": "Synthesis of (+/-)-8,12-trans-delta5-en-cis-11-KETO-14,15-trans-en-16-R,S-hydroxyprostanoic acid methyl ester. The synthesis of (+/-)-8,12-trans-delta5-en-cis-11-keto-14,15-trans-en-16-R,S-hydroxyprostanoic acid methyl ester (XIII) from 2-allyl-2-cyclopentenone (I) is described. The key products are the conjugate enone (IX) or the acetylenic secondary alcohol (X) derived from 2-propargyl-2-cyclopentenone (II)."} {"id": "PMID:1278364", "title": "Synthesis of new derivatives of the 4,5-diphenyloxazole series.", "content": "In continuation of earlier studies carried out in the field of 2-amino- and 2-aminoalkyl-4,5-diphenyloxazoles, some of which had shown anti-inflammatory, analgesic and platelet antiaggregating properties, a series of 2-alkylthio-4,5-diphenyloxazoles was prepared.", "contents": "Synthesis of new derivatives of the 4,5-diphenyloxazole series. In continuation of earlier studies carried out in the field of 2-amino- and 2-aminoalkyl-4,5-diphenyloxazoles, some of which had shown anti-inflammatory, analgesic and platelet antiaggregating properties, a series of 2-alkylthio-4,5-diphenyloxazoles was prepared."} {"id": "PMID:1278365", "title": "Synthesis of (+/-)-8,12-trans-delta5-en-cis-9-KETO-14,15-en-trans-16-R,S-hydroxyprostanoic acid methyl ester.", "content": "A new synthesis of (+/-)-8,12-trans-delta5-en-cis-9-keto-14,15-en-trans-16-R,S-hydroxyprostanoic acid methyl ester (VII) from 2-allyl-2-cyclopentenone (I) is described, for which a lateral chain link process, opposite to that previously reported (4), is adopted.", "contents": "Synthesis of (+/-)-8,12-trans-delta5-en-cis-9-KETO-14,15-en-trans-16-R,S-hydroxyprostanoic acid methyl ester. A new synthesis of (+/-)-8,12-trans-delta5-en-cis-9-keto-14,15-en-trans-16-R,S-hydroxyprostanoic acid methyl ester (VII) from 2-allyl-2-cyclopentenone (I) is described, for which a lateral chain link process, opposite to that previously reported (4), is adopted."} {"id": "PMID:1278398", "title": "The effect of portacaval transposition of hepatic cholesterol-7alpha-hydroxylase activity in the rat.", "content": "Portacaval anastomosis in the rat results in an increase in the activity of the liver microsomal cholesterol-7alpha-hydroxylase enzyme system. The increase in the activity of this oxygenase occurs despite a decrease in the total amount of cytochrome p450 in the liver microsomes after portacaval anastomosis. It is possible to increase further the activity of the cholesterol-7alpha-hydroxylase enzyme in these portacaval shunted animals by feeding them on a diet containing a bile salt sequestering agent. This suggests that one of the factors influencing the activity of the liver microsomal cholesterol-7alpha-hydroxylase enzyme may be the concentration of bile salts reaching the liver from the blood plasma. Portacaval anastomosis in the rat tended to achieve a small decrease in the plasma cholesterol concentration.", "contents": "The effect of portacaval transposition of hepatic cholesterol-7alpha-hydroxylase activity in the rat. Portacaval anastomosis in the rat results in an increase in the activity of the liver microsomal cholesterol-7alpha-hydroxylase enzyme system. The increase in the activity of this oxygenase occurs despite a decrease in the total amount of cytochrome p450 in the liver microsomes after portacaval anastomosis. It is possible to increase further the activity of the cholesterol-7alpha-hydroxylase enzyme in these portacaval shunted animals by feeding them on a diet containing a bile salt sequestering agent. This suggests that one of the factors influencing the activity of the liver microsomal cholesterol-7alpha-hydroxylase enzyme may be the concentration of bile salts reaching the liver from the blood plasma. Portacaval anastomosis in the rat tended to achieve a small decrease in the plasma cholesterol concentration."} {"id": "PMID:1278401", "title": "Proteins dealing with N-ethylmaleimide inhibition of pig heart mitochondrial phosphate transport system.", "content": "Our data clearly demonstrate that protective effect of phosphate and protective effect of mersalyl against NEM-inhibition of phosphate transport act at the level of two kinds of proteins. (1)Two major components are phosphate and nigericin NEM sensitive. According to our previous data [13] it has been also demonstrated that these two proteins components are valinomycin NEM sensitive (results not shown here) suggesting a relationship between these proteins and the energy linked proton translocation process. Relationships between these proteins and the phosphate translocation process are not evident and are under further investigations. (2) Two other insoluble major components localised at the level of the subparticular fraction are mersalyl NEM sensitive. We can suggest that these proteins are implicated in the translocation of phosphate in pig heart mitochondria.", "contents": "Proteins dealing with N-ethylmaleimide inhibition of pig heart mitochondrial phosphate transport system. Our data clearly demonstrate that protective effect of phosphate and protective effect of mersalyl against NEM-inhibition of phosphate transport act at the level of two kinds of proteins. (1)Two major components are phosphate and nigericin NEM sensitive. According to our previous data [13] it has been also demonstrated that these two proteins components are valinomycin NEM sensitive (results not shown here) suggesting a relationship between these proteins and the energy linked proton translocation process. Relationships between these proteins and the phosphate translocation process are not evident and are under further investigations. (2) Two other insoluble major components localised at the level of the subparticular fraction are mersalyl NEM sensitive. We can suggest that these proteins are implicated in the translocation of phosphate in pig heart mitochondria."} {"id": "PMID:1278448", "title": "Respiratory rhythmicity in the cat.", "content": "Brain stem respiratory neuron activity in the cat was studied in relation to efferent outflow (phrenic discharge) under the influence of several forcing inputs: 1) CO2 tension: hypocapnia produces disappearance of firing in some neurons, and conversion of respiratory-modulated to continuous (tonic) firing in others. 2) Lung inflation: during the Bruer-Hering reflex, some neurons have \"classical\" responses and others have \"paradoxical\" responses (i.e., opposite in direction to peripheral discharge). 3) Electrical stimulation: stimulus trains to the pneumotaxic center region (rostral lateral pons) produce phase-switching, whose threshold is: a) sharp (indicating action of positive-feedback mechanisms), and b) dependent on timing of stimulus delivery (indicating continuous excitability changes during each respiratory phase). Auto- and crosscorrelation analysis revealed the existence of short-term interactions between: a) medullary inspiratory (I) neurons and phrenic motoneurons; b) pairs of medullary I neurons; c) medullary I neurons and expiratory (E) neurons. A model of the respiratory oscillator is presented, in which the processes of conversion of tonic to phasic activity and switching of the respiratory phases are explained by recurrent excitatory and inhibitory loops.", "contents": "Respiratory rhythmicity in the cat. Brain stem respiratory neuron activity in the cat was studied in relation to efferent outflow (phrenic discharge) under the influence of several forcing inputs: 1) CO2 tension: hypocapnia produces disappearance of firing in some neurons, and conversion of respiratory-modulated to continuous (tonic) firing in others. 2) Lung inflation: during the Bruer-Hering reflex, some neurons have \"classical\" responses and others have \"paradoxical\" responses (i.e., opposite in direction to peripheral discharge). 3) Electrical stimulation: stimulus trains to the pneumotaxic center region (rostral lateral pons) produce phase-switching, whose threshold is: a) sharp (indicating action of positive-feedback mechanisms), and b) dependent on timing of stimulus delivery (indicating continuous excitability changes during each respiratory phase). Auto- and crosscorrelation analysis revealed the existence of short-term interactions between: a) medullary inspiratory (I) neurons and phrenic motoneurons; b) pairs of medullary I neurons; c) medullary I neurons and expiratory (E) neurons. A model of the respiratory oscillator is presented, in which the processes of conversion of tonic to phasic activity and switching of the respiratory phases are explained by recurrent excitatory and inhibitory loops."} {"id": "PMID:1278449", "title": "Neuronal control of respiration in decapod crustacea.", "content": "Respiratory exchange in decapod crustacea requires the coordinated activity of the heart and the scaphognathites, appendages which ventilate the gills. There is common central nervous system neuronal modulation of both autogenically active systems as well as direct neuronal communication between both systems. The heart and scaphognathites also respond directly to oxygen tension. The neuronal control of the scaphognathites also respond directly to oxygen tension. The neuronal control of the scaphognathites is analyzed at several levels. Particular attention is directed toward the means by which the innately organized and stereotyped motor pattern for forward beating can be altered to produce reversed beating. The importance of sensory feedback in maintaining normal rates of scaphognathite beating is noted. And the phenomenon of bilateral coordination between the morphologically independent scaphognathites is described. Several different models of parts of the over-all scaphognathite neuronal circuitry are presented for heuristic purposes.", "contents": "Neuronal control of respiration in decapod crustacea. Respiratory exchange in decapod crustacea requires the coordinated activity of the heart and the scaphognathites, appendages which ventilate the gills. There is common central nervous system neuronal modulation of both autogenically active systems as well as direct neuronal communication between both systems. The heart and scaphognathites also respond directly to oxygen tension. The neuronal control of the scaphognathites also respond directly to oxygen tension. The neuronal control of the scaphognathites is analyzed at several levels. Particular attention is directed toward the means by which the innately organized and stereotyped motor pattern for forward beating can be altered to produce reversed beating. The importance of sensory feedback in maintaining normal rates of scaphognathite beating is noted. And the phenomenon of bilateral coordination between the morphologically independent scaphognathites is described. Several different models of parts of the over-all scaphognathite neuronal circuitry are presented for heuristic purposes."} {"id": "PMID:1278450", "title": "Sensory and central nervous control of gill ventilation in Limulus.", "content": "The gills of Limulus are ventilated by a metachronal rhythm of movements of five pairs of gill plates. A gill plate is promoted and remoted by action of alternating nerve impulse bursts to antagonist promotor and remotor muscles. The motor output pattern is centrally generated, requiring no sensory feedback. Intracellularly recorded rhythmic activity of respiratory motoneurons consists of cyclic depolarization and spiking, and repolarization. The repolarizations have reversal potentials that indicate that motoneuron burst terminations result from synaptic inhibition. Intracellular and antidromic stimulation of motoneurons has little effect on other motoneurons. This apparent lack of interaction between motoneurons indicates that the central respiratory pattern is generated at interneuronal levels. Proprioceptive reflexes are present; they play little role in modulating the centrally generated motor pattern, but they are capable of partially entraining the rhythm when all gill plates are cycled at frequencies near the respiratory rate. Respiratory rate in intact animals is proportional to the ambient oxygen content, respiration ceasing in an anoxic environment. This oxygen dependence may result from sensory input from external oxygen receptors located in the cuticle between the coxae of the walking legs and within the lamellas of the book gills. The intercoxal units are inhibited by anoxia. Three classes of units are recorded from the gills: units excited by oxygen, units inhibited by oxygen, and units whose mechanosensitivity is oxygen dependent. These external oxygen receptors may modulate ventilation via command fibers present in the ventral nerve cord.", "contents": "Sensory and central nervous control of gill ventilation in Limulus. The gills of Limulus are ventilated by a metachronal rhythm of movements of five pairs of gill plates. A gill plate is promoted and remoted by action of alternating nerve impulse bursts to antagonist promotor and remotor muscles. The motor output pattern is centrally generated, requiring no sensory feedback. Intracellularly recorded rhythmic activity of respiratory motoneurons consists of cyclic depolarization and spiking, and repolarization. The repolarizations have reversal potentials that indicate that motoneuron burst terminations result from synaptic inhibition. Intracellular and antidromic stimulation of motoneurons has little effect on other motoneurons. This apparent lack of interaction between motoneurons indicates that the central respiratory pattern is generated at interneuronal levels. Proprioceptive reflexes are present; they play little role in modulating the centrally generated motor pattern, but they are capable of partially entraining the rhythm when all gill plates are cycled at frequencies near the respiratory rate. Respiratory rate in intact animals is proportional to the ambient oxygen content, respiration ceasing in an anoxic environment. This oxygen dependence may result from sensory input from external oxygen receptors located in the cuticle between the coxae of the walking legs and within the lamellas of the book gills. The intercoxal units are inhibited by anoxia. Three classes of units are recorded from the gills: units excited by oxygen, units inhibited by oxygen, and units whose mechanosensitivity is oxygen dependent. These external oxygen receptors may modulate ventilation via command fibers present in the ventral nerve cord."} {"id": "PMID:1278452", "title": "Intrauterine gonadal development.", "content": "This review article summarizes the intrauterine gonadal development and differentiation of both male and female human embryos and fetuses. It describes in detail (1) the organization of the indifferent gonad and its seeding by the extra-gonadal germ cells, (2) the development of the duct systems before sex differentiation, and (3) the controlling mechanism of differentiation of the ovaries and testes. Timetable for the development of the human male and female reproductive systems have been compiled from the literature.", "contents": "Intrauterine gonadal development. This review article summarizes the intrauterine gonadal development and differentiation of both male and female human embryos and fetuses. It describes in detail (1) the organization of the indifferent gonad and its seeding by the extra-gonadal germ cells, (2) the development of the duct systems before sex differentiation, and (3) the controlling mechanism of differentiation of the ovaries and testes. Timetable for the development of the human male and female reproductive systems have been compiled from the literature."} {"id": "PMID:1278453", "title": "Cytologic features of oocytes in the adult human ovary.", "content": "A broad survey of the cytologic features of follicular oocytes from sections of adult ovaries from donors with normal menstrual cycles, from patients with polycystic ovarian disease, and from patients treated with estrogen and progesterone for gynecologic disorders with no apparent ovarian pathology has been made in this study. On the basis of light microscopic observations, four basic types of oocytes could be recognized: (1) oocytes with nuclei containing diffused or filamentous chromatin, (2) oocytes with metaphase I chromosomes or an extruded polar body, (3) oocytes with nuclei possessing massive clumps of chromatin frequently associated with the nucleolus, and (4) degenerating oocytes with no distinguishing cytologic features. The numbers of oocytes in these different groups varied with the reproductive state of the donors: 34 to 35% were type 1 during proliferative and secretory phases; mature oocytes type 2 were 3.3%, and were found only during the late proliferative phase; and 41 to 46% were type 3 during both phases of the menstrucal cycle. Large numbers of oocytes from polycystic ovaries (77%) and from ovaries of patients treated with steroids (86%) were degenerating and frequently contained massive clumps of chromatin material associated with the nucleolus.", "contents": "Cytologic features of oocytes in the adult human ovary. A broad survey of the cytologic features of follicular oocytes from sections of adult ovaries from donors with normal menstrual cycles, from patients with polycystic ovarian disease, and from patients treated with estrogen and progesterone for gynecologic disorders with no apparent ovarian pathology has been made in this study. On the basis of light microscopic observations, four basic types of oocytes could be recognized: (1) oocytes with nuclei containing diffused or filamentous chromatin, (2) oocytes with metaphase I chromosomes or an extruded polar body, (3) oocytes with nuclei possessing massive clumps of chromatin frequently associated with the nucleolus, and (4) degenerating oocytes with no distinguishing cytologic features. The numbers of oocytes in these different groups varied with the reproductive state of the donors: 34 to 35% were type 1 during proliferative and secretory phases; mature oocytes type 2 were 3.3%, and were found only during the late proliferative phase; and 41 to 46% were type 3 during both phases of the menstrucal cycle. Large numbers of oocytes from polycystic ovaries (77%) and from ovaries of patients treated with steroids (86%) were degenerating and frequently contained massive clumps of chromatin material associated with the nucleolus."} {"id": "PMID:1278454", "title": "The LEM device in an immediate postpartum contraception program.", "content": "Experience with the LEM intrauterine device in an immediate postpartum program at the Jose Fabella Memorial Hospital, Manila, Philippines, is reported. During a 6-month period, the LEM was inserted in 1359 women immediately after normal term deliveries. The early expulsion rate was high, but removals for bleeding or pain were minimal. Pregnancy rates during the second 6 months of use were higher than those reported previously for postpartum insertions of the LEM device.", "contents": "The LEM device in an immediate postpartum contraception program. Experience with the LEM intrauterine device in an immediate postpartum program at the Jose Fabella Memorial Hospital, Manila, Philippines, is reported. During a 6-month period, the LEM was inserted in 1359 women immediately after normal term deliveries. The early expulsion rate was high, but removals for bleeding or pain were minimal. Pregnancy rates during the second 6 months of use were higher than those reported previously for postpartum insertions of the LEM device."} {"id": "PMID:1278455", "title": "The effect of D-norgestrel, 30 micrograms, on the oral glucose tolerance test, including insulin levels, in Thai women.", "content": "The effect of D-norgestrel, 30 mug, on the oral glucose tolerance test was studied in 49 Thai women. There was a significant elevation of the blood glucose level at 60 minutes during the test in women who had taken D-norgestrel for 6 and 12 months. Insulin levels in the blood were significantly elevated over control levels in both groups of women at 90, 120, 150, and 180 minutes during the test. There was no difference in the results obtained at 6 months and 12 months. There was also no significant difference in the fasting blood glucose or insulin levels in the three groups of women. The results indicate that D-norestrel at a daily dose of 30 mug has an effect on carbohydrate metabolism in Thai women.", "contents": "The effect of D-norgestrel, 30 micrograms, on the oral glucose tolerance test, including insulin levels, in Thai women. The effect of D-norgestrel, 30 mug, on the oral glucose tolerance test was studied in 49 Thai women. There was a significant elevation of the blood glucose level at 60 minutes during the test in women who had taken D-norgestrel for 6 and 12 months. Insulin levels in the blood were significantly elevated over control levels in both groups of women at 90, 120, 150, and 180 minutes during the test. There was no difference in the results obtained at 6 months and 12 months. There was also no significant difference in the fasting blood glucose or insulin levels in the three groups of women. The results indicate that D-norestrel at a daily dose of 30 mug has an effect on carbohydrate metabolism in Thai women."} {"id": "PMID:1278456", "title": "Artificial insemination donor: clinical and psychologic aspects.", "content": "Forty-four sterile sterile couples in whom the main cause of infertility was the male factor were investigated. Artificial insemination donor (AID) was performed, timed according to the basal body temperature chart. It was found that it is important to match not only the physical appearance of the couple to that of the donor but also the blood group of at least one of the future parents. Patients were interviewed by a psychologist in order to define their marital relationship, their attitude toward the infertility, their feelings about AID in comparison to adoption, their attitude toward the donor and pregnancy, and their attitude toward their physician. The role of the psycholgist in AID treatment was found to be important for careful selection of cases. He can also guide and prepare these couples to face family life in the future.", "contents": "Artificial insemination donor: clinical and psychologic aspects. Forty-four sterile sterile couples in whom the main cause of infertility was the male factor were investigated. Artificial insemination donor (AID) was performed, timed according to the basal body temperature chart. It was found that it is important to match not only the physical appearance of the couple to that of the donor but also the blood group of at least one of the future parents. Patients were interviewed by a psychologist in order to define their marital relationship, their attitude toward the infertility, their feelings about AID in comparison to adoption, their attitude toward the donor and pregnancy, and their attitude toward their physician. The role of the psycholgist in AID treatment was found to be important for careful selection of cases. He can also guide and prepare these couples to face family life in the future."} {"id": "PMID:1278457", "title": "A new method for evaluating cervical penetrability using daily aspirated and stored cervical mucus.", "content": "Cervical mucus samples from 33 women undergoing fertility work-up and married to normospermic husbands were aspirated daily with a tuberculin syringe during the periovulatory period. Samples were transferred to polyethylene tubing, sealed, and stored at 4 degrees C for 7 to 14 days. In vitro sperm penetration tests were performed in each case, using only one sample of husband's semen with all of the mucus samples that were collected during one cycle. Preliminary studies with 50 samples of cervical mucus taken at random showed that no difference in physicochemical and penetrability properties existed between fresh mucus and mucus stored for 10 to 14 days. Very often the optimal penetrability of the cervical mucus occurred on unpredictable days. In contrast, many tests performed on days which would have been predetermined for in vivo postocital tests were poor; consequently, those in vivo tests would have been falsely interpreted as negative. This new test using daily aspirated and stored mucus, which is simple to perform, is valuable mainly because it may eliminate the false negative results of other penetration tests. In this way the diagnosis of a truly hostile cervix may be more accurate.", "contents": "A new method for evaluating cervical penetrability using daily aspirated and stored cervical mucus. Cervical mucus samples from 33 women undergoing fertility work-up and married to normospermic husbands were aspirated daily with a tuberculin syringe during the periovulatory period. Samples were transferred to polyethylene tubing, sealed, and stored at 4 degrees C for 7 to 14 days. In vitro sperm penetration tests were performed in each case, using only one sample of husband's semen with all of the mucus samples that were collected during one cycle. Preliminary studies with 50 samples of cervical mucus taken at random showed that no difference in physicochemical and penetrability properties existed between fresh mucus and mucus stored for 10 to 14 days. Very often the optimal penetrability of the cervical mucus occurred on unpredictable days. In contrast, many tests performed on days which would have been predetermined for in vivo postocital tests were poor; consequently, those in vivo tests would have been falsely interpreted as negative. This new test using daily aspirated and stored mucus, which is simple to perform, is valuable mainly because it may eliminate the false negative results of other penetration tests. In this way the diagnosis of a truly hostile cervix may be more accurate."} {"id": "PMID:1278458", "title": "Studies on the physiology and biochemistry of mammalian epididymis: effect of flutamide, a nonsteroidal antiandrogen, on the epididymis of the rat.", "content": "The effect of flutamide (Sch 13521; 4'-nitro-3'-trifluoromethylisobutyranilide), a nonsteroidal antiandrogen, on male rat genital organs was studied. Administered at a dose of 25 mg/kg body weight daily for 30 days, flutamide caused a significant increase in the weight of the testis but had no effect on spermatogenesis and Leydig cell morphology. The secretory activity of the epididymis, as evidenced by the level of glycerylphosphoryl-choline and sialic acid, either remained unaffected or was stimulated. There was a significant decrease in seminal vesicle and ventral prostate weight and in the fructose content of the coagulating gland. The anti-androgen at the dose used did not affect the fertility of the rats. The significance of these findings is viewed in relation to the hypothesis of a differential threshold requirement of androgen for the epididymis and the accessory sex glands. The potentiality of antiandrogens as extragonadal antifertility agents in the male is discussed.", "contents": "Studies on the physiology and biochemistry of mammalian epididymis: effect of flutamide, a nonsteroidal antiandrogen, on the epididymis of the rat. The effect of flutamide (Sch 13521; 4'-nitro-3'-trifluoromethylisobutyranilide), a nonsteroidal antiandrogen, on male rat genital organs was studied. Administered at a dose of 25 mg/kg body weight daily for 30 days, flutamide caused a significant increase in the weight of the testis but had no effect on spermatogenesis and Leydig cell morphology. The secretory activity of the epididymis, as evidenced by the level of glycerylphosphoryl-choline and sialic acid, either remained unaffected or was stimulated. There was a significant decrease in seminal vesicle and ventral prostate weight and in the fructose content of the coagulating gland. The anti-androgen at the dose used did not affect the fertility of the rats. The significance of these findings is viewed in relation to the hypothesis of a differential threshold requirement of androgen for the epididymis and the accessory sex glands. The potentiality of antiandrogens as extragonadal antifertility agents in the male is discussed."} {"id": "PMID:1278460", "title": "Artificial insemination using homologous semen: a review of 158 cases.", "content": "One hundred fifty-eight women underwent artificial insemination with homologous semen (AIH) in an attempt to achieve conception. Only 15 (9.5%) were successful. Women with anatomical abnormalities were not excluded from the study and they were less successful than the normal women, but results were disappointing in both groups. The most frequently recorded indication for AIH was decreased density or motility of the husband's sperm, but pregnancy occurred in only 2 of the 48 cases in which sperm count was consistently less than 50 X 10(6)/ml and in only 3 of the 63 cases in which sperm motility was consistently less than 60%. When several semen analyses revealed considerable fluctuation in semen quality, the chances for impregnation by natural means appeared to be greater than the likelihood of success with AIH. The procedure does not seem to compensate for diminished count or motility, does not seem to be of particular value in cases of unexplained infertility, and appears to be indicated only in very special cases, if at all.", "contents": "Artificial insemination using homologous semen: a review of 158 cases. One hundred fifty-eight women underwent artificial insemination with homologous semen (AIH) in an attempt to achieve conception. Only 15 (9.5%) were successful. Women with anatomical abnormalities were not excluded from the study and they were less successful than the normal women, but results were disappointing in both groups. The most frequently recorded indication for AIH was decreased density or motility of the husband's sperm, but pregnancy occurred in only 2 of the 48 cases in which sperm count was consistently less than 50 X 10(6)/ml and in only 3 of the 63 cases in which sperm motility was consistently less than 60%. When several semen analyses revealed considerable fluctuation in semen quality, the chances for impregnation by natural means appeared to be greater than the likelihood of success with AIH. The procedure does not seem to compensate for diminished count or motility, does not seem to be of particular value in cases of unexplained infertility, and appears to be indicated only in very special cases, if at all."} {"id": "PMID:1278461", "title": "Pituitary-testicular axis in patients on lithium therapy.", "content": "Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were studied in 10 patients undergoing lithium therapy. Testosterone levels were below the normal range in 7 of the 10 patients. FSH levels were high in two patients and LH levels were high in one. The effects of lithium on the pituitary-testicular axis are discussed.", "contents": "Pituitary-testicular axis in patients on lithium therapy. Plasma follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels were studied in 10 patients undergoing lithium therapy. Testosterone levels were below the normal range in 7 of the 10 patients. FSH levels were high in two patients and LH levels were high in one. The effects of lithium on the pituitary-testicular axis are discussed."} {"id": "PMID:1278462", "title": "A method for collecting motile spermatozoa from human semen.", "content": "Spermatozoa migrate rapidly into a diluent brought into contact with semen. When this process was used to collect sperm in a diluent contained in Pasteur pipettes that were dipped into semen for 1 hour, concentrations of spermatozoa ranging from 0.6 to 5.7 X 10(6) cells/ml were obtained. This method yielded sperm suspensions free of seminal plasma and populations of spermatozoa that had increased motility ratings compared with the original semen. In contrast, removal of the seminal plasma by a procedure involving three dilutions and two gentle centrifugations resulted in a decrease in the average motility ratings. Determinations were made of the electrolyte, energy substrate, and trace element content of preovulatory human tubal fluid. A sperm diluent having an electrolyte composition similar to that of tubal fluid was formulated and used for collecting spermatozoa. Population of spermatozoa that migrated from semen into this diluent had significantly greater mean velocities than sperm in the semen. Moreover, the diluent proved to be a favourable medium for significantly delaying the deterioration of sperm progression over a 24-hour period.", "contents": "A method for collecting motile spermatozoa from human semen. Spermatozoa migrate rapidly into a diluent brought into contact with semen. When this process was used to collect sperm in a diluent contained in Pasteur pipettes that were dipped into semen for 1 hour, concentrations of spermatozoa ranging from 0.6 to 5.7 X 10(6) cells/ml were obtained. This method yielded sperm suspensions free of seminal plasma and populations of spermatozoa that had increased motility ratings compared with the original semen. In contrast, removal of the seminal plasma by a procedure involving three dilutions and two gentle centrifugations resulted in a decrease in the average motility ratings. Determinations were made of the electrolyte, energy substrate, and trace element content of preovulatory human tubal fluid. A sperm diluent having an electrolyte composition similar to that of tubal fluid was formulated and used for collecting spermatozoa. Population of spermatozoa that migrated from semen into this diluent had significantly greater mean velocities than sperm in the semen. Moreover, the diluent proved to be a favourable medium for significantly delaying the deterioration of sperm progression over a 24-hour period."} {"id": "PMID:1278463", "title": "Round-headed human spermatozoa.", "content": "Ultrastructural investigation of two cases of round-headed spermatozoa from human ejaculates revealed the existence of two different pathomorphogenetic types. Case 1 represented round-headed spermatozoa of the Schirren and Holstein type caused by loss of the abnormally formed acrosome during spermiogenesis and the missing nuclear transformation. In case 2 a primary maturing inhibition was responsible for the round-headed feature of the spermatozoa; the normally flattened, conical nucleus and acrosomal cap were surrounded by huge droplets of ample cytoplasm. Secondary degenerative changes contributed to the decreased motility of these round-headed spermatozoa. Therapeutic trials for this oligospermic patient showed that an increase in cell count to values in the low-normal range and a drastic reduction in the percentage of round-headed cells (from 80% to 47%) could be achieved. The Schirren and Holstein type, however, must be regarded as absolutely infertile due to the absence of an acrosome and its intrinsic enzymes.", "contents": "Round-headed human spermatozoa. Ultrastructural investigation of two cases of round-headed spermatozoa from human ejaculates revealed the existence of two different pathomorphogenetic types. Case 1 represented round-headed spermatozoa of the Schirren and Holstein type caused by loss of the abnormally formed acrosome during spermiogenesis and the missing nuclear transformation. In case 2 a primary maturing inhibition was responsible for the round-headed feature of the spermatozoa; the normally flattened, conical nucleus and acrosomal cap were surrounded by huge droplets of ample cytoplasm. Secondary degenerative changes contributed to the decreased motility of these round-headed spermatozoa. Therapeutic trials for this oligospermic patient showed that an increase in cell count to values in the low-normal range and a drastic reduction in the percentage of round-headed cells (from 80% to 47%) could be achieved. The Schirren and Holstein type, however, must be regarded as absolutely infertile due to the absence of an acrosome and its intrinsic enzymes."} {"id": "PMID:1278464", "title": "The value of scrotal thermography as compared with selective retrograde venography of the internal spermatic vein for the diagnosis of \"subclinical\" varicocele.", "content": "The accuracy of scrotal thermography as a diagnostic method to confirm or detect spermatic venous reflux in patients with palpable and subclinical varicocele, respectively, was evaluated. In all, 118 scrotal thermograms were performed in 110 patients, and the results were compared with the findings by selective retrograde venography of the internal spermatic vein whenever required. Normal thermograms were recorded in 23 oligospermic men without varicocele. Of 39 patients with palpable varicocele, 37 had abnormal thermograms; normal recordings occurred in 2 patients with associated unilateral testicular atrophy. Among 36 men suspected of having subclinical varicocele, 19 had abnormal thermograms and 16 presented reflux on the venogram. Venography was performed in 5 of the remaining 17 men with normal thermograms; only 1 had reflux. Screening for varicocele by means of scrotal thermography thus revealed reflux in 16 of 36 patients with unexplained infertility. Postoperative thermograms were disturbed in 6 of 20 cases, 5 of which presented reflux. Only 1 of 14 postoperative patients with normal thermograms underwent venography, and no reflux was demonstrable. Both the difference in temperature between the affected and contralateral hemiscrotum and the area of hyperthermia were significantly greater in patients with grades II and III varicocele, compared with those with subclinical and grade I varicocele. It is concluded that scrotal thermography is a valuable screening method for the detection of spermatic venous reflux. The technique allows selection of patients to be subjected to retrograde venography.", "contents": "The value of scrotal thermography as compared with selective retrograde venography of the internal spermatic vein for the diagnosis of \"subclinical\" varicocele. The accuracy of scrotal thermography as a diagnostic method to confirm or detect spermatic venous reflux in patients with palpable and subclinical varicocele, respectively, was evaluated. In all, 118 scrotal thermograms were performed in 110 patients, and the results were compared with the findings by selective retrograde venography of the internal spermatic vein whenever required. Normal thermograms were recorded in 23 oligospermic men without varicocele. Of 39 patients with palpable varicocele, 37 had abnormal thermograms; normal recordings occurred in 2 patients with associated unilateral testicular atrophy. Among 36 men suspected of having subclinical varicocele, 19 had abnormal thermograms and 16 presented reflux on the venogram. Venography was performed in 5 of the remaining 17 men with normal thermograms; only 1 had reflux. Screening for varicocele by means of scrotal thermography thus revealed reflux in 16 of 36 patients with unexplained infertility. Postoperative thermograms were disturbed in 6 of 20 cases, 5 of which presented reflux. Only 1 of 14 postoperative patients with normal thermograms underwent venography, and no reflux was demonstrable. Both the difference in temperature between the affected and contralateral hemiscrotum and the area of hyperthermia were significantly greater in patients with grades II and III varicocele, compared with those with subclinical and grade I varicocele. It is concluded that scrotal thermography is a valuable screening method for the detection of spermatic venous reflux. The technique allows selection of patients to be subjected to retrograde venography."} {"id": "PMID:1278465", "title": "Characterization of phosphoglycerate kinase from human spermatozoa.", "content": "We have confirmed the presence of a unique electrophoretic isoenzyme of phosphoglycerate kinase (PGK) in homogenate extracts of human sperm. No genetic variation was found in 30 individual specimens tested. However, immunologic neutralization studies indicate that the sperm PGK is different from red cell PGK.", "contents": "Characterization of phosphoglycerate kinase from human spermatozoa. We have confirmed the presence of a unique electrophoretic isoenzyme of phosphoglycerate kinase (PGK) in homogenate extracts of human sperm. No genetic variation was found in 30 individual specimens tested. However, immunologic neutralization studies indicate that the sperm PGK is different from red cell PGK."} {"id": "PMID:1278466", "title": "Purification and characterization of a sperm-coating antigen from human seminal plasma.", "content": "A sperm-coating antigen has been purified from human seminal plasma by a combination of fractionation methods including ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl cellulose ion-exchange chromatography. The purified antigen was demonstrated to be immunologically identical sperm-coating antigen, not derived from blood serum but having immunologically cross-relating antigens in milk and saliva, and a glycoprotein with a molecular weight of approximately 33,000. The purpose of purifying this antigen was discussed.", "contents": "Purification and characterization of a sperm-coating antigen from human seminal plasma. A sperm-coating antigen has been purified from human seminal plasma by a combination of fractionation methods including ammonium sulfate precipitation, Sephadex G-100 gel filtration, and diethylaminoethyl cellulose ion-exchange chromatography. The purified antigen was demonstrated to be immunologically identical sperm-coating antigen, not derived from blood serum but having immunologically cross-relating antigens in milk and saliva, and a glycoprotein with a molecular weight of approximately 33,000. The purpose of purifying this antigen was discussed."} {"id": "PMID:1278467", "title": "Effects of progesterone on labeling of soluble proteins and glycoproteins in rabbit endometrium.", "content": "An in vitro test system was used to study in vivo effects of progesterone on synthesis and secretion of total proteins and glycoproteins in rabbit endometrium. Endometrial explants incubated in Eagle's minimal essential medium containing radioactive leucine and N-acetylglucosamine were found to synthesize soluble proteins readily, including glycoproteins. Furthermore, significant amounts of newly synthesized proteins, including blastokinin, were released by the tissues into the incubation medium. In addition, in vitro synthesis and release of labeled proteins by estrogen-primed endometrial tissue (E-primed tissue) was significantly enhanced by exposure of the tissues to progesterone in vivo. Double-labeling studies demonstrated qualitative as well as quantitative differences in peptide synthesis between E-primed tissues and E-primed, progesterone-treated tissues. Progesterone also stimulated both the synthesis and the release of glycoprotein by E-primed tissues. These studies, therefore, suggest that progesterone regulates qualitatively and quantitatively the synthesis and secretion of total proteins, including glyco-proteins, in rabbit endometrium.", "contents": "Effects of progesterone on labeling of soluble proteins and glycoproteins in rabbit endometrium. An in vitro test system was used to study in vivo effects of progesterone on synthesis and secretion of total proteins and glycoproteins in rabbit endometrium. Endometrial explants incubated in Eagle's minimal essential medium containing radioactive leucine and N-acetylglucosamine were found to synthesize soluble proteins readily, including glycoproteins. Furthermore, significant amounts of newly synthesized proteins, including blastokinin, were released by the tissues into the incubation medium. In addition, in vitro synthesis and release of labeled proteins by estrogen-primed endometrial tissue (E-primed tissue) was significantly enhanced by exposure of the tissues to progesterone in vivo. Double-labeling studies demonstrated qualitative as well as quantitative differences in peptide synthesis between E-primed tissues and E-primed, progesterone-treated tissues. Progesterone also stimulated both the synthesis and the release of glycoprotein by E-primed tissues. These studies, therefore, suggest that progesterone regulates qualitatively and quantitatively the synthesis and secretion of total proteins, including glyco-proteins, in rabbit endometrium."} {"id": "PMID:1278487", "title": "[Concentration of urea in blood and organs during muscular activity].", "content": "Muscular activity increases the content of urea in blood, liver, and muscles equally. The urea content in the kidney, however, either decreases or does not change at all, increasing only after an exhausting work or during the rest. The amount of protein in the diet influences upon the urea quantity in the organism, but the level of it's change under the action of muscular activity remains practically identical in the regime of the different protein nutrition. The activity of arginase in the liver and muscles is equally changed with the changes of the urea content in the blood and tissues.", "contents": "[Concentration of urea in blood and organs during muscular activity]. Muscular activity increases the content of urea in blood, liver, and muscles equally. The urea content in the kidney, however, either decreases or does not change at all, increasing only after an exhausting work or during the rest. The amount of protein in the diet influences upon the urea quantity in the organism, but the level of it's change under the action of muscular activity remains practically identical in the regime of the different protein nutrition. The activity of arginase in the liver and muscles is equally changed with the changes of the urea content in the blood and tissues."} {"id": "PMID:1278488", "title": "[Heat content of the body as a basic parameter of thermoregulation].", "content": "With the aid of thermometry and calorimetry, the role of the organism's heat degree for the vasomotor response of the ear skin was studied in the rabbit. The calorimetric temperature was constant (19-21 degrees C) throughout the experiment. The heat threshold varied from 86 cal/kg to 320 cal/kg, depending on the different initial heat degrees in the animal. The increase in the organism's heat degree is concluded to be the main mechanism for initiation of the heat loss responses.", "contents": "[Heat content of the body as a basic parameter of thermoregulation]. With the aid of thermometry and calorimetry, the role of the organism's heat degree for the vasomotor response of the ear skin was studied in the rabbit. The calorimetric temperature was constant (19-21 degrees C) throughout the experiment. The heat threshold varied from 86 cal/kg to 320 cal/kg, depending on the different initial heat degrees in the animal. The increase in the organism's heat degree is concluded to be the main mechanism for initiation of the heat loss responses."} {"id": "PMID:1278489", "title": "[Osmo- and ionic liver receptors].", "content": "Role of the liver receptors in osmo- and ionic homeostasis regulation was studied in unanesthetized dogs. The presence of selective sodium-and potassium-sensitive receptors was shown in the liver receptor field. Stimulation of the ionic receptors evokes ADH-induced antidiuretic and specific ionuretic renal response. Impulses depressing diuresis were found to spread mainly in the posterior roots of the spinal cord, while those changing the ion excretion - in the n. vagi.", "contents": "[Osmo- and ionic liver receptors]. Role of the liver receptors in osmo- and ionic homeostasis regulation was studied in unanesthetized dogs. The presence of selective sodium-and potassium-sensitive receptors was shown in the liver receptor field. Stimulation of the ionic receptors evokes ADH-induced antidiuretic and specific ionuretic renal response. Impulses depressing diuresis were found to spread mainly in the posterior roots of the spinal cord, while those changing the ion excretion - in the n. vagi."} {"id": "PMID:1278492", "title": "[The role of several brain stem structures in activation of the neocortex and motor reflexes in chronically premesencephalic cats].", "content": "Chronic experiments were carried out in 18 cats. After premesencephalic section of the brain-stem, the neocortex can be activated both spontaneously and in response to the posterior hypothalamus or the forepaw skin stimulation. After bilateral lesions in the posterior hypothalamus, neither spontaneous nor the forepaw-skin stimulation-produced activation of the neocortex, was observed. Excitation of the mesencephalic RF is accompanied by activation of motor reflexes. A conclusion was made that the posterior hypothalamus, independently of the mesencephalic RF, is capable of activating the neocortex, while the mesencephalic RF, independently of the rostral structures, is responsible for the motor reflex activation.", "contents": "[The role of several brain stem structures in activation of the neocortex and motor reflexes in chronically premesencephalic cats]. Chronic experiments were carried out in 18 cats. After premesencephalic section of the brain-stem, the neocortex can be activated both spontaneously and in response to the posterior hypothalamus or the forepaw skin stimulation. After bilateral lesions in the posterior hypothalamus, neither spontaneous nor the forepaw-skin stimulation-produced activation of the neocortex, was observed. Excitation of the mesencephalic RF is accompanied by activation of motor reflexes. A conclusion was made that the posterior hypothalamus, independently of the mesencephalic RF, is capable of activating the neocortex, while the mesencephalic RF, independently of the rostral structures, is responsible for the motor reflex activation."} {"id": "PMID:1278493", "title": "[The effect of low-frequency electric stimulation of the caudate nucleus on the electrical activity of the cortex and on the sleep-wakefulness cycle].", "content": "In cats, the effect of low-frequency electric stimulation of the caudate nucleus on electric activity of neo- and archipaleocortex and on wakefulness-sleep cycle, was studied. The data obtained suggest: 1) at threshold and suprathreshold single electric shocks applied to the caudate nucleus they evoked potential occurs more readily in the sensorimotor area of the neocortex than in the dorsal hippocampus. At 2-6/sec stimulation the evoked potentials in the hippocampus are facilitated and become very stable, whereas in the sensorimotor cortex the most obvious responses occur at the 6-8/sec frequency. However, the evoked potentials are variable in the sensorimotor cortex, and at prolonged 8-12/sec stimulation spindle activity soon develops; 2) behavioral correlate of the synchronized activity in the neo- and archipaleocortical structures during low-frequency stimulation of the caudate nucleus, may involve development of drowsiness with the cessation of stimulation, however, both the EEG and behavioral signs of the drowsiness disappear. The onset of drowsiness following withdrawal of the caudate stimulation, is a rare phenomenon only occurring because of an occasional coincidence of the stimulation with the spontaneous onset of natural sleep; 3) low-frequency caudate stimulation entailing the ECoG synchronization does not cause the transition of paradoxical phase into the slow-wave phase of sleep, and as soon as the stimulation ceases its normal structure recovers. However, if the stimulation of the caudate nucleus is repeated several times in one paradoxical phase, this would shorten the subsequent slow-wave phase and accelerate the onset of the next paradoxical phase; 4) prolonged low-frequency stimulation of the caudate nucleus causing the ECoG synchronization results in a considerable change of wakefulness-sleep cycle in the post-stimulation period: a decrease in the total time of slow-wave sleep due to shortening of its different phases, and an increase in the total amount of paradoxical sleep because of the onset of its phases is rendered more frequent. This effect is more obvious in the first half of the 8-hr cycle.", "contents": "[The effect of low-frequency electric stimulation of the caudate nucleus on the electrical activity of the cortex and on the sleep-wakefulness cycle]. In cats, the effect of low-frequency electric stimulation of the caudate nucleus on electric activity of neo- and archipaleocortex and on wakefulness-sleep cycle, was studied. The data obtained suggest: 1) at threshold and suprathreshold single electric shocks applied to the caudate nucleus they evoked potential occurs more readily in the sensorimotor area of the neocortex than in the dorsal hippocampus. At 2-6/sec stimulation the evoked potentials in the hippocampus are facilitated and become very stable, whereas in the sensorimotor cortex the most obvious responses occur at the 6-8/sec frequency. However, the evoked potentials are variable in the sensorimotor cortex, and at prolonged 8-12/sec stimulation spindle activity soon develops; 2) behavioral correlate of the synchronized activity in the neo- and archipaleocortical structures during low-frequency stimulation of the caudate nucleus, may involve development of drowsiness with the cessation of stimulation, however, both the EEG and behavioral signs of the drowsiness disappear. The onset of drowsiness following withdrawal of the caudate stimulation, is a rare phenomenon only occurring because of an occasional coincidence of the stimulation with the spontaneous onset of natural sleep; 3) low-frequency caudate stimulation entailing the ECoG synchronization does not cause the transition of paradoxical phase into the slow-wave phase of sleep, and as soon as the stimulation ceases its normal structure recovers. However, if the stimulation of the caudate nucleus is repeated several times in one paradoxical phase, this would shorten the subsequent slow-wave phase and accelerate the onset of the next paradoxical phase; 4) prolonged low-frequency stimulation of the caudate nucleus causing the ECoG synchronization results in a considerable change of wakefulness-sleep cycle in the post-stimulation period: a decrease in the total time of slow-wave sleep due to shortening of its different phases, and an increase in the total amount of paradoxical sleep because of the onset of its phases is rendered more frequent. This effect is more obvious in the first half of the 8-hr cycle."} {"id": "PMID:1278494", "title": "[Changes in the activity of the cat sensomotor cortex under heterosensory stimulation].", "content": "In immobilized cats, the sensorymotor neurons were shown, in the course of habituation to the rhythmic light stimulation (1/sec), to start responding to stimuli of other modalities (somatic) when the latter were presented during the functional recovery cycle following the light stimulation. The habituation to the light stimuli did not occur when they were followed by a somatic stimulus with 100-300 msec delay. The data obtained seem to reflect the reconstruction occurring in the functional state of the sensory system.", "contents": "[Changes in the activity of the cat sensomotor cortex under heterosensory stimulation]. In immobilized cats, the sensorymotor neurons were shown, in the course of habituation to the rhythmic light stimulation (1/sec), to start responding to stimuli of other modalities (somatic) when the latter were presented during the functional recovery cycle following the light stimulation. The habituation to the light stimuli did not occur when they were followed by a somatic stimulus with 100-300 msec delay. The data obtained seem to reflect the reconstruction occurring in the functional state of the sensory system."} {"id": "PMID:1278495", "title": "[The effect of hippocampal stimulation on the evoked electrical activity of different brain structures].", "content": "The functional relationships of the dorsal and ventral hippocampus and entorhinal area were studied in cats. The dorsal hippocampus was shown to suppress the electric activity and evoked responses to entorhinal stimulation in the ventral hippocampus and other structures. The dorsal hippocampus inhibits evoked responses to skin stimulation in entorhinal area and ventral hippocampus. The ventral hippocampus produced opposite effects. The functional differences of the dorsal and ventral hippocampus suggest different connections with entorhinal area.", "contents": "[The effect of hippocampal stimulation on the evoked electrical activity of different brain structures]. The functional relationships of the dorsal and ventral hippocampus and entorhinal area were studied in cats. The dorsal hippocampus was shown to suppress the electric activity and evoked responses to entorhinal stimulation in the ventral hippocampus and other structures. The dorsal hippocampus inhibits evoked responses to skin stimulation in entorhinal area and ventral hippocampus. The ventral hippocampus produced opposite effects. The functional differences of the dorsal and ventral hippocampus suggest different connections with entorhinal area."} {"id": "PMID:1278496", "title": "[The interaction of symmetrical cortical descending influences on lumbar motoneurons].", "content": "Postsynaptic potentials (PSPs) of the cat motoneurons elicited by stimulation of contralateral and ipsilateral motor cortex, and their changes during combination of both kinds of stimulation were studied with use of the intracellular recording technique. For elicitation of ipsilateral PSPs, the cortex stimulation of greater intensity was needed as compared with contralateral activation. The ipsilateral synaptic reactions had a longer latency and time of segmental delay than the contralateral ones. Conditioning stimulation of the ipsilateral cortex exerted an inhibitory effect upon contralateral cortically evoked EPSP and IPSP of motoneurons and upon potential recorded at the spinal cord surface. Suppression of conditioned PSPs occurred without changes of their sign or pattern in most cases. The data obtained suggest that inhibitory interaction of cortically evoked descending activities involves segmentary inhibitory interneurons and is realized at an interneuronal level and/or at the membrane of the motoneurons.", "contents": "[The interaction of symmetrical cortical descending influences on lumbar motoneurons]. Postsynaptic potentials (PSPs) of the cat motoneurons elicited by stimulation of contralateral and ipsilateral motor cortex, and their changes during combination of both kinds of stimulation were studied with use of the intracellular recording technique. For elicitation of ipsilateral PSPs, the cortex stimulation of greater intensity was needed as compared with contralateral activation. The ipsilateral synaptic reactions had a longer latency and time of segmental delay than the contralateral ones. Conditioning stimulation of the ipsilateral cortex exerted an inhibitory effect upon contralateral cortically evoked EPSP and IPSP of motoneurons and upon potential recorded at the spinal cord surface. Suppression of conditioned PSPs occurred without changes of their sign or pattern in most cases. The data obtained suggest that inhibitory interaction of cortically evoked descending activities involves segmentary inhibitory interneurons and is realized at an interneuronal level and/or at the membrane of the motoneurons."} {"id": "PMID:1278498", "title": "[An analysis of EEG rhythm changes following micropolarization of several brain structures].", "content": "With the aid of the EEG special statistical analysis, micropolarization of the temporal cortex of hypothalamus was shown to entail abrupt alterations of the theta-, alpha-, and beta-rhythms in the temporal and motor cortex, hypothalamus, and the midbrain RF. The changes of the biorhythms (their correlation, thresholds of occurring, connection of the local and distant shifts) are regarded as reflecting some fine regulation of the structures' functional condition as well as mutual influences of the cortex and the deep brain structures which tell on modulation of mnemic processes.", "contents": "[An analysis of EEG rhythm changes following micropolarization of several brain structures]. With the aid of the EEG special statistical analysis, micropolarization of the temporal cortex of hypothalamus was shown to entail abrupt alterations of the theta-, alpha-, and beta-rhythms in the temporal and motor cortex, hypothalamus, and the midbrain RF. The changes of the biorhythms (their correlation, thresholds of occurring, connection of the local and distant shifts) are regarded as reflecting some fine regulation of the structures' functional condition as well as mutual influences of the cortex and the deep brain structures which tell on modulation of mnemic processes."} {"id": "PMID:1278499", "title": "[Distribution of carbon dioxide and oxygen tension in neurons of the cerebral cortex and their surrounding tissue].", "content": "Mathematical model of the capillary network with a neuron body in the center makes it possible to calculate CO2 and O2 pressures at different points of the neuron and the tissue. On this model the influence of arterial pCO2 on the O2 transport from the capillaries to neuron and surrounding tissue was studied. The pCO2 in the brain tissue, in contrast to pO2, was found to be distributed evenly. Considerable arterial pCO2 changes (up to 20 torr) resulted in but small pO2 in the brain tissue (about 5 torr). The data obtained corroborate the idea of the CO2 important role in regulation of cerebral circulation.", "contents": "[Distribution of carbon dioxide and oxygen tension in neurons of the cerebral cortex and their surrounding tissue]. Mathematical model of the capillary network with a neuron body in the center makes it possible to calculate CO2 and O2 pressures at different points of the neuron and the tissue. On this model the influence of arterial pCO2 on the O2 transport from the capillaries to neuron and surrounding tissue was studied. The pCO2 in the brain tissue, in contrast to pO2, was found to be distributed evenly. Considerable arterial pCO2 changes (up to 20 torr) resulted in but small pO2 in the brain tissue (about 5 torr). The data obtained corroborate the idea of the CO2 important role in regulation of cerebral circulation."} {"id": "PMID:1278500", "title": "[Consequences of partial deafferentation of the hindlimb in cats].", "content": "The hindlimb deafferentation was found to entail disorders of the motor activity and sensitivity, as well as a decrease in the evoked activity in the cortical somatosensory areas, although in a lesser degree than transection of the same amount of dorsal roots innervating the forelimbs. Apparently, the afferent organization of the cat hindlimb is different from that of the forelimb. This accounts for preservation of a part of the afferent inflow from periphery to the cortex after partial deafferentation, as well as for the considerable rehabilitation of functions of deafferented hindlimb.", "contents": "[Consequences of partial deafferentation of the hindlimb in cats]. The hindlimb deafferentation was found to entail disorders of the motor activity and sensitivity, as well as a decrease in the evoked activity in the cortical somatosensory areas, although in a lesser degree than transection of the same amount of dorsal roots innervating the forelimbs. Apparently, the afferent organization of the cat hindlimb is different from that of the forelimb. This accounts for preservation of a part of the afferent inflow from periphery to the cortex after partial deafferentation, as well as for the considerable rehabilitation of functions of deafferented hindlimb."} {"id": "PMID:1278502", "title": "[The mechanism of skin receptor excitation during temperature stimulation].", "content": "The skin was found to contract under the cold effect, and pilomotors were contracting during stimulation of the C efferents. The pilomotors were shown to take no part in the temperature deformation of the skin. Using the colliding impulses method, the skin mechanoreceptors were shown to be activated both by contractions of the pilomotors and by the temperature deformation of the skin. The possibility to activate the skin mechanoreceptors by the temperature deformation of the skin collagen, is discussed.", "contents": "[The mechanism of skin receptor excitation during temperature stimulation]. The skin was found to contract under the cold effect, and pilomotors were contracting during stimulation of the C efferents. The pilomotors were shown to take no part in the temperature deformation of the skin. Using the colliding impulses method, the skin mechanoreceptors were shown to be activated both by contractions of the pilomotors and by the temperature deformation of the skin. The possibility to activate the skin mechanoreceptors by the temperature deformation of the skin collagen, is discussed."} {"id": "PMID:1278503", "title": "[Conditions for indefatiguability of skeletal muscles].", "content": "Studies in rats with indirect stimulation of the m. triepssurae showed that the muscle worked for scores of hours without any signs of fatigue. Such working ability of the neuro-muscular apparatus (NMA) is only possible if the loads do not exceed 0.15-0.20 of the maximal tetanic strength, and the stimulation frequency is about 40/sec. Such parameters of stimulation permite to achieve unfatiguability of muscle in isometric contraction regimen. The constant amplitude of action potentials during the whole period of work, and quick relaxation of the contracting muscle working for many hours indicate the intensity of electric and metabolic processes in the muscle.", "contents": "[Conditions for indefatiguability of skeletal muscles]. Studies in rats with indirect stimulation of the m. triepssurae showed that the muscle worked for scores of hours without any signs of fatigue. Such working ability of the neuro-muscular apparatus (NMA) is only possible if the loads do not exceed 0.15-0.20 of the maximal tetanic strength, and the stimulation frequency is about 40/sec. Such parameters of stimulation permite to achieve unfatiguability of muscle in isometric contraction regimen. The constant amplitude of action potentials during the whole period of work, and quick relaxation of the contracting muscle working for many hours indicate the intensity of electric and metabolic processes in the muscle."} {"id": "PMID:1278505", "title": "[Tecto-cortical connections in the rat visual system].", "content": "Electric stimulation of the colliculus superior evokes potentials (EP) in the visual cortex of the ipsilateral hemisphere of the rat brain, their localization coinciding with the zone of flash-evoked potentials. EPs of maximal amplitude were observed during stimulation of the central layers of the colliculus superior. Short latency of the EPs (3.2 +/- 1.1 msec; p less than 0.05) and the relevant morphological data suggest a single relay in rat's tecto-cortical visual system. The data are discussed in regard to the comparative telecephalisation of the retino-tectal system in submammalian vertebrates and in mammals.", "contents": "[Tecto-cortical connections in the rat visual system]. Electric stimulation of the colliculus superior evokes potentials (EP) in the visual cortex of the ipsilateral hemisphere of the rat brain, their localization coinciding with the zone of flash-evoked potentials. EPs of maximal amplitude were observed during stimulation of the central layers of the colliculus superior. Short latency of the EPs (3.2 +/- 1.1 msec; p less than 0.05) and the relevant morphological data suggest a single relay in rat's tecto-cortical visual system. The data are discussed in regard to the comparative telecephalisation of the retino-tectal system in submammalian vertebrates and in mammals."} {"id": "PMID:1278506", "title": "[The effect of microiontophoretic administration of acetylcholine on evoked activity of visual cortex neurons subjected to direct cortical stimulation].", "content": "Reactions of visual cortical neurons (field 17) were studied in unanesthetized curarized cats. Neuronal responses to direct electric stimulation of the 18th and the 19th fields were studied after microiontophoretic administration of acetylcholine--chloride through 2-channel microelectrodes. The acetylcholine effect upon the primary discharge and the first trace pause, was specifically organized. Some neurons reacted differently under acetylcholine to stimulation of the 18th and the 19th fields. Participation of acetylcholine in information processing by transcortical mechanisms, is discussed.", "contents": "[The effect of microiontophoretic administration of acetylcholine on evoked activity of visual cortex neurons subjected to direct cortical stimulation]. Reactions of visual cortical neurons (field 17) were studied in unanesthetized curarized cats. Neuronal responses to direct electric stimulation of the 18th and the 19th fields were studied after microiontophoretic administration of acetylcholine--chloride through 2-channel microelectrodes. The acetylcholine effect upon the primary discharge and the first trace pause, was specifically organized. Some neurons reacted differently under acetylcholine to stimulation of the 18th and the 19th fields. Participation of acetylcholine in information processing by transcortical mechanisms, is discussed."} {"id": "PMID:1278507", "title": "[Laminar analysis of commissural evoked potentials of the hippocampus following microiontophoretic administration of glutamate].", "content": "The hippocampal commissural evoked potentials (EP) were studied by means of microiontophoretic application of glutamate in unanesthetized immobilized rats. Near the reversion level, glutamate strongly decreased the primary positive component of the commissural EP, with a parallel enhancement of the negativity. An increase in the stimulus intensity restored the EP shape. In the stratum radiatum, glutamate considerably increased the deep commissural response. Using paired microelectrodes, the effect of glutamate disappeared at a distance more than 100 m from the phoretic electrode tip. When delivering paired stimuli with 20-200 msec interval, the second EP was changed under the glutamate effect.", "contents": "[Laminar analysis of commissural evoked potentials of the hippocampus following microiontophoretic administration of glutamate]. The hippocampal commissural evoked potentials (EP) were studied by means of microiontophoretic application of glutamate in unanesthetized immobilized rats. Near the reversion level, glutamate strongly decreased the primary positive component of the commissural EP, with a parallel enhancement of the negativity. An increase in the stimulus intensity restored the EP shape. In the stratum radiatum, glutamate considerably increased the deep commissural response. Using paired microelectrodes, the effect of glutamate disappeared at a distance more than 100 m from the phoretic electrode tip. When delivering paired stimuli with 20-200 msec interval, the second EP was changed under the glutamate effect."} {"id": "PMID:1278509", "title": "[Central nystagmus and its interaction with optokinetic and reversive postoptokinetic nystagmus].", "content": "In rabbits, the interaction of central nystagmus (CN) with optokinetic (OKN) or reversive postoptokinetic (RPN) nystagmi (irrespective of their direction) resulted in their inhibition. Cessation of electric stimulation led to restoration of OKN or RPN. Coincidence of CN with OKN or RPN in the direction led to a considerable shortening of the period from the moment of electric stimulation till the resulting rhythmic nystagmus, as well as till the rhythmic OKN or RPN.", "contents": "[Central nystagmus and its interaction with optokinetic and reversive postoptokinetic nystagmus]. In rabbits, the interaction of central nystagmus (CN) with optokinetic (OKN) or reversive postoptokinetic (RPN) nystagmi (irrespective of their direction) resulted in their inhibition. Cessation of electric stimulation led to restoration of OKN or RPN. Coincidence of CN with OKN or RPN in the direction led to a considerable shortening of the period from the moment of electric stimulation till the resulting rhythmic nystagmus, as well as till the rhythmic OKN or RPN."} {"id": "PMID:1278511", "title": "[Functional characteristics of rapidly adapting mechanoreceptor units of the rat mammary gland nipple].", "content": "Two types of rapidly adapting mechanosensitive units were found in the teat of the rat mammary gland (RAI and RAII). Neither was spontaneously active. 10% of the units were RAII and had the functional characteristics of \"transient\" receptors. The relation between the average frequency of discharge and the velocity of displacement at a constant displacement amplitude was linear for RAI. The latency of the first spike decreased when indentation velocity increased. The number and frequency of afferent impulses decreased at a repeated mechanical stimulation. Vibratory tuning points were in the range 10--25 Hz for RAI. RAI units were not directionally sensitive to the teat displacement.", "contents": "[Functional characteristics of rapidly adapting mechanoreceptor units of the rat mammary gland nipple]. Two types of rapidly adapting mechanosensitive units were found in the teat of the rat mammary gland (RAI and RAII). Neither was spontaneously active. 10% of the units were RAII and had the functional characteristics of \"transient\" receptors. The relation between the average frequency of discharge and the velocity of displacement at a constant displacement amplitude was linear for RAI. The latency of the first spike decreased when indentation velocity increased. The number and frequency of afferent impulses decreased at a repeated mechanical stimulation. Vibratory tuning points were in the range 10--25 Hz for RAI. RAI units were not directionally sensitive to the teat displacement."} {"id": "PMID:1278513", "title": "[The functional heterogeneity of the synapses of the frog sartorius muscle].", "content": "Three main types of neuro-muscular junctions were revealed by means of the e.p.p. quantum content and the e.p.p. dynamics during high-frequency stimulation. Heterogeneity of synaptic apparatus seems to be mainly due to different intensities of quantum release. Subctances facilitating neuro-muscular transmission (Ca2+ ions, imidazol) were more effective in myoneural junctions with low e.p.p. quantum content, while depressing chemical agents (acetylcholine, tubocurarine) exerted a more potent effect in junctions with high quantum content.", "contents": "[The functional heterogeneity of the synapses of the frog sartorius muscle]. Three main types of neuro-muscular junctions were revealed by means of the e.p.p. quantum content and the e.p.p. dynamics during high-frequency stimulation. Heterogeneity of synaptic apparatus seems to be mainly due to different intensities of quantum release. Subctances facilitating neuro-muscular transmission (Ca2+ ions, imidazol) were more effective in myoneural junctions with low e.p.p. quantum content, while depressing chemical agents (acetylcholine, tubocurarine) exerted a more potent effect in junctions with high quantum content."} {"id": "PMID:1278514", "title": "[Transformation of the strength characteristics and work capacity of antagonistic muscles during rabbit postnatal ontogenesis].", "content": "In the rabbit muscles-antagonists in situ, the dependence of work (A) of isotonic contraction of the load (P) was studied in different age periods. For the range of loads 1.5 - Popt greater than or equal to P greater than or equal to 0.5 - Popt, the results were found to be satisfactorily approximated by the equation A = A opt = a - /Popt - P/2, where Aopt, Popt, and a are constants. The experiments revealed that the ratio Aopt. m. gastrocnemius/Aopt. m. tibialis anterior sharply increases during realization of the standing posture (16-18 days) and then drops at the grown-up age. Similar age changes were revealed for the Popt parameters ratio of the same muscles. At the same time, the respective ratio of the a parameters of the muscles under study drops sharply by the 16-18th day age, practically remaining the same afterwards. The obtained changes of the strength parameters and working ability of skeletal muscles in the course of postnatal ontogenesis are regarded from the standpoint of peculiarities of the skeletal muscles functioning at different age periods and with regard to ecological peculiarities of individual development of rabbits.", "contents": "[Transformation of the strength characteristics and work capacity of antagonistic muscles during rabbit postnatal ontogenesis]. In the rabbit muscles-antagonists in situ, the dependence of work (A) of isotonic contraction of the load (P) was studied in different age periods. For the range of loads 1.5 - Popt greater than or equal to P greater than or equal to 0.5 - Popt, the results were found to be satisfactorily approximated by the equation A = A opt = a - /Popt - P/2, where Aopt, Popt, and a are constants. The experiments revealed that the ratio Aopt. m. gastrocnemius/Aopt. m. tibialis anterior sharply increases during realization of the standing posture (16-18 days) and then drops at the grown-up age. Similar age changes were revealed for the Popt parameters ratio of the same muscles. At the same time, the respective ratio of the a parameters of the muscles under study drops sharply by the 16-18th day age, practically remaining the same afterwards. The obtained changes of the strength parameters and working ability of skeletal muscles in the course of postnatal ontogenesis are regarded from the standpoint of peculiarities of the skeletal muscles functioning at different age periods and with regard to ecological peculiarities of individual development of rabbits."} {"id": "PMID:1278515", "title": "[Catecholamine metabolism during adaptation to muscular activity].", "content": "In rats, an increased O-methylation in the brain, heart, liver, and in the m. gastrocnemius as well as an increased intensity of oxidative desamination in the liver were revealed after muscular training and administration of retabolile. After additional 70-min swimming, in intact rats the MAO activity was raised in the liver, and the intensity of O-methylation - in the muscle and the heart. In rats adapted to muscular training, no increase of O-methylation in the heart or MAO activity in the liver was observed which may be regarded as an adaptive hypometabolic reaction of the organism for a more \"ecomonic\" usage of the catecholamines. An increase of the catecholamines contents was revealed in adrenals of the rats after training and retabolile administration. The 70-min swimming obviously suppressed the catecholamines synthesis in the rat adrenals. The synthetic activity of the adrenals in trained animals was also decreased, although insignificantly, which resulted from the preliminary adaptation of the organism to muscular activity.", "contents": "[Catecholamine metabolism during adaptation to muscular activity]. In rats, an increased O-methylation in the brain, heart, liver, and in the m. gastrocnemius as well as an increased intensity of oxidative desamination in the liver were revealed after muscular training and administration of retabolile. After additional 70-min swimming, in intact rats the MAO activity was raised in the liver, and the intensity of O-methylation - in the muscle and the heart. In rats adapted to muscular training, no increase of O-methylation in the heart or MAO activity in the liver was observed which may be regarded as an adaptive hypometabolic reaction of the organism for a more \"ecomonic\" usage of the catecholamines. An increase of the catecholamines contents was revealed in adrenals of the rats after training and retabolile administration. The 70-min swimming obviously suppressed the catecholamines synthesis in the rat adrenals. The synthetic activity of the adrenals in trained animals was also decreased, although insignificantly, which resulted from the preliminary adaptation of the organism to muscular activity."} {"id": "PMID:1278516", "title": "[The existence of a thrombocyte refractory state].", "content": "The degree of ADP-induced platelet aggregation was considerably decreased during incubation of platelet-rich plasma with ADP. The data obtained showed that neither inhibitory action of the excess of adenosine, nor ADP breakdown in the plasma could account for this phenomenon. The results seem to indicate the significance of refractory state of platelets for the regulation of their aggregability.", "contents": "[The existence of a thrombocyte refractory state]. The degree of ADP-induced platelet aggregation was considerably decreased during incubation of platelet-rich plasma with ADP. The data obtained showed that neither inhibitory action of the excess of adenosine, nor ADP breakdown in the plasma could account for this phenomenon. The results seem to indicate the significance of refractory state of platelets for the regulation of their aggregability."} {"id": "PMID:1278517", "title": "[Filtration-absorption function of the lungs during hemodynamic stress in the pulmonary circulation].", "content": "The transcapillary fluid exchange in the lung during elevation of the pulmonary venous pressure (PVP) was studied in cats. The weighing technique in vivo for a lung lobe, the comparison of the hematocrit of pulmonary arterial and venous blood, and the measurement of the outflow from the lung lobe at constant volume perfusion were used for the estimation of the filtration rate. The latter was not linearly related to PVP. Capillary filtration coefficient was about 0.040-0.055 ml/min/100 g tissue/mm Hg during the PVP rise by 5-10 mm Hg, and about 0.068-0.087 at PVP raised by 20-25 mm Hg. Under conditions of the open chest, the fluid accumulation was observed in the extravascular compartment of the lung even after relatively small and short PVP elevations.", "contents": "[Filtration-absorption function of the lungs during hemodynamic stress in the pulmonary circulation]. The transcapillary fluid exchange in the lung during elevation of the pulmonary venous pressure (PVP) was studied in cats. The weighing technique in vivo for a lung lobe, the comparison of the hematocrit of pulmonary arterial and venous blood, and the measurement of the outflow from the lung lobe at constant volume perfusion were used for the estimation of the filtration rate. The latter was not linearly related to PVP. Capillary filtration coefficient was about 0.040-0.055 ml/min/100 g tissue/mm Hg during the PVP rise by 5-10 mm Hg, and about 0.068-0.087 at PVP raised by 20-25 mm Hg. Under conditions of the open chest, the fluid accumulation was observed in the extravascular compartment of the lung even after relatively small and short PVP elevations."} {"id": "PMID:1278525", "title": "[The effect of low-frequency stimulation of the diencephalon on the topogram of cortical potentials in freely moving rabbits].", "content": "The spatio-temporal organization of the cortical potentials in rabbits was investigated by means of comparison of successive electroencephalotopograms. This systemic organization was characterized by the potentials' sagittal gradient and its inversion within the 4-6/sec range due to higher amplitudes in the frontal cortical areas, - during natural transition from the active to passive behavior as well as after low-frequency stimulation of the thalamic midline nuclei and of the hypothalamic supraoptic area. Single stimuli applied to the structures under study ordinarily prevented any obvious active behavioral periods, although entailed no long-lasting changes in the rest-activity dynamics.", "contents": "[The effect of low-frequency stimulation of the diencephalon on the topogram of cortical potentials in freely moving rabbits]. The spatio-temporal organization of the cortical potentials in rabbits was investigated by means of comparison of successive electroencephalotopograms. This systemic organization was characterized by the potentials' sagittal gradient and its inversion within the 4-6/sec range due to higher amplitudes in the frontal cortical areas, - during natural transition from the active to passive behavior as well as after low-frequency stimulation of the thalamic midline nuclei and of the hypothalamic supraoptic area. Single stimuli applied to the structures under study ordinarily prevented any obvious active behavioral periods, although entailed no long-lasting changes in the rest-activity dynamics."} {"id": "PMID:1278526", "title": "[Representation of cutaneous sensitivity in the cat red nucleus].", "content": "Responses of the red nucleus neurons to the skin stimulation in unanestethized chronic cats showed most of the neurons to have wide receptive fields with areas stimulation of which caused an extremely intense and stable activation of respective neurons. The somatotopic principle of the cutaneous representation in the red nucleus was revealed. Destruction of the cerebellar nuclei and sensory motor cortex lowered the spontaneous activity of the red nucleus neurons, changed their responses to the skin stimulation, and caused the narrowing and the redistribution of the peripheral receptive fields preserving, however, the somatotopic character of the cutaneous representation in the red nucleus.", "contents": "[Representation of cutaneous sensitivity in the cat red nucleus]. Responses of the red nucleus neurons to the skin stimulation in unanestethized chronic cats showed most of the neurons to have wide receptive fields with areas stimulation of which caused an extremely intense and stable activation of respective neurons. The somatotopic principle of the cutaneous representation in the red nucleus was revealed. Destruction of the cerebellar nuclei and sensory motor cortex lowered the spontaneous activity of the red nucleus neurons, changed their responses to the skin stimulation, and caused the narrowing and the redistribution of the peripheral receptive fields preserving, however, the somatotopic character of the cutaneous representation in the red nucleus."} {"id": "PMID:1278527", "title": "[Functional significance of alpha- and beta-adrenoreceptors in structures of the stropallidal system].", "content": "Microapplication of noradrenaline, isadrine, phentolamine, and propranole to neuroanal populations of the striatum in curarized unanesthetized rabbits revealed an inhibitory and stimulatory effects of noradrenaline and isadrine. A specific antagonism between alpha- and beta-adrenomimetics and respective alpha- and beta-adrenoblocking agents, was noted. Noradenaline seems to have a very important mediatory function in the adrenergic synapases of the striatum. Existence of alpha- and beta-adrenoreceptors with different functions in different brain areas, is suggested.", "contents": "[Functional significance of alpha- and beta-adrenoreceptors in structures of the stropallidal system]. Microapplication of noradrenaline, isadrine, phentolamine, and propranole to neuroanal populations of the striatum in curarized unanesthetized rabbits revealed an inhibitory and stimulatory effects of noradrenaline and isadrine. A specific antagonism between alpha- and beta-adrenomimetics and respective alpha- and beta-adrenoblocking agents, was noted. Noradenaline seems to have a very important mediatory function in the adrenergic synapases of the striatum. Existence of alpha- and beta-adrenoreceptors with different functions in different brain areas, is suggested."} {"id": "PMID:1278530", "title": "[The effect of thyroid hormones on inhibition of monosynaptic extensor reflexes].", "content": "In thyreotoxic cats with intact or transected spinal cord, intensity of direct and presynaptic inhibition induced by a single volley in a flexor nerve afferent fibers was diminished and the delayed postsynaptic (polysynaptic) inhibition from the skin afferent fibers was more intense than in control cats. The mechanisms for the thyroid hormone effect on the cerebrospinal control of the extensor reflex inhibition, are discussed.", "contents": "[The effect of thyroid hormones on inhibition of monosynaptic extensor reflexes]. In thyreotoxic cats with intact or transected spinal cord, intensity of direct and presynaptic inhibition induced by a single volley in a flexor nerve afferent fibers was diminished and the delayed postsynaptic (polysynaptic) inhibition from the skin afferent fibers was more intense than in control cats. The mechanisms for the thyroid hormone effect on the cerebrospinal control of the extensor reflex inhibition, are discussed."} {"id": "PMID:1278531", "title": "[Impulse flows of crayfish neurons].", "content": "During adequate stimulation of the uropods hairs (1/sec.), comparative analysis of adaptive changes due to the impulse flows from the receptor and motor neurons of the 6th abdominal ganglion of the crayfish revealed that, in afferent neurons with a slow-frequency spontaneous activity, the first signs of adaptation occurred by the 25 th-30 th min. after beginning of the stimulation, and in neurons with a high firing rate-by the 35 th-40 th min.", "contents": "[Impulse flows of crayfish neurons]. During adequate stimulation of the uropods hairs (1/sec.), comparative analysis of adaptive changes due to the impulse flows from the receptor and motor neurons of the 6th abdominal ganglion of the crayfish revealed that, in afferent neurons with a slow-frequency spontaneous activity, the first signs of adaptation occurred by the 25 th-30 th min. after beginning of the stimulation, and in neurons with a high firing rate-by the 35 th-40 th min."} {"id": "PMID:1278532", "title": "[Detemination of the hearing characteristics of the dolphin by the evoked potential method].", "content": "The evoked potentials were recorded in the dolphin Tursiops truncatus auditory cortex with implanted electrodes. Thresholds of the responses to sounds (clicks, noises and tones) ranged from 10(-2) to 10(-3) Pa. Noises evoked potentials with the lowest threshold of about 1-10(-3) Pa. The evoked responses were elicited both by on and off sound effects as well as by change of the sound intensity or frequency. The thresholds of responses to changes of intensity were about 0.6-0.8 db (7-10%); those of responses to changes of frequency were about 0.25%. The temporal summation could be observed up to 20 msec.", "contents": "[Detemination of the hearing characteristics of the dolphin by the evoked potential method]. The evoked potentials were recorded in the dolphin Tursiops truncatus auditory cortex with implanted electrodes. Thresholds of the responses to sounds (clicks, noises and tones) ranged from 10(-2) to 10(-3) Pa. Noises evoked potentials with the lowest threshold of about 1-10(-3) Pa. The evoked responses were elicited both by on and off sound effects as well as by change of the sound intensity or frequency. The thresholds of responses to changes of intensity were about 0.6-0.8 db (7-10%); those of responses to changes of frequency were about 0.25%. The temporal summation could be observed up to 20 msec."} {"id": "PMID:1278533", "title": "[The state of anticoagulant system of animals following injections of purified thrombin and N-acetyl-thrombin].", "content": "I. v. administration of N-acetyl-thrombin, similar to thrombin, increases the fermentative fibrinolytic potency of the plasma, although to a lesser extent. This is also expressed in the increased esterase activity of the plasma and euglobulin fraction. When blocking the forming plasmin, esterase activity is observed in kallekreine. (The inhibitory effect of plasma after N-acetyl-thrombin administration tells also on the nonfermentative fibrinolytic activity of the Fibrinogen-Heparin complex, activity of the latter dropping practically to the zero level. Warming up at 60 degrees C decreases the nonfermentative fibrinolytic activity of the complex N-acetyl-thrombin (thrombin-esterase) does not provoke the activation of the second anticoagulang system, while the native thrombin does it.", "contents": "[The state of anticoagulant system of animals following injections of purified thrombin and N-acetyl-thrombin]. I. v. administration of N-acetyl-thrombin, similar to thrombin, increases the fermentative fibrinolytic potency of the plasma, although to a lesser extent. This is also expressed in the increased esterase activity of the plasma and euglobulin fraction. When blocking the forming plasmin, esterase activity is observed in kallekreine. (The inhibitory effect of plasma after N-acetyl-thrombin administration tells also on the nonfermentative fibrinolytic activity of the Fibrinogen-Heparin complex, activity of the latter dropping practically to the zero level. Warming up at 60 degrees C decreases the nonfermentative fibrinolytic activity of the complex N-acetyl-thrombin (thrombin-esterase) does not provoke the activation of the second anticoagulang system, while the native thrombin does it."} {"id": "PMID:1278535", "title": "[Vasopressin concentration in the blood and sensitivity of the cardiovascular system to it during aging].", "content": "With aging the content of the blood vasopressin increases. In old animals smaller doses of vasopressin induce coronary insufficiency (rise of T wave, shift of S-T segment, disorders of the atrio-ventricular conductivity). On continuous administration of vasopressin (during a month), arterial hypertension appears only in old animals due to increase in cardiac output, stroke volume at unchanged cardiac rhythm, and to some decrease in the total peripheral resistance.", "contents": "[Vasopressin concentration in the blood and sensitivity of the cardiovascular system to it during aging]. With aging the content of the blood vasopressin increases. In old animals smaller doses of vasopressin induce coronary insufficiency (rise of T wave, shift of S-T segment, disorders of the atrio-ventricular conductivity). On continuous administration of vasopressin (during a month), arterial hypertension appears only in old animals due to increase in cardiac output, stroke volume at unchanged cardiac rhythm, and to some decrease in the total peripheral resistance."} {"id": "PMID:1278537", "title": "[Enzyme activity of the mucous membrane of the rat small intestine during heat exposure].", "content": "In acute experiments, the amylolytic, invertase, glycyl-L-tyrosindipeptidase, monoglyceridlipase,and alkaline phosphatase activity of the mucosa homogenate of the rat small intestine was studied 4, 24, 48 and 72 hrs after a two-hour exposure to 36-37 and 40-41 degrees C. No decrease in the activity of any of the ferments was observed. Exposure to heat is concluded to lead to the changes of small intestine ferments spectrum. The character of these changes depends on the heat stress degree and its duration.", "contents": "[Enzyme activity of the mucous membrane of the rat small intestine during heat exposure]. In acute experiments, the amylolytic, invertase, glycyl-L-tyrosindipeptidase, monoglyceridlipase,and alkaline phosphatase activity of the mucosa homogenate of the rat small intestine was studied 4, 24, 48 and 72 hrs after a two-hour exposure to 36-37 and 40-41 degrees C. No decrease in the activity of any of the ferments was observed. Exposure to heat is concluded to lead to the changes of small intestine ferments spectrum. The character of these changes depends on the heat stress degree and its duration."} {"id": "PMID:1278538", "title": "[Sodium release from tissue paracellular space under the influence of angiotensin II].", "content": "Angiotensin II added in vitro in concentration 3-10(-10) M increased the sodium release from the aorta wall, myocardium, and skin in the rat. The action persisted at 2 degrees C and in presence of monoiodacetate. Sodium loading increased the sensitivity of aorta to the action of the angiotensin. The angiotensin-induced sodium release seems to be a step towards the myotropic action of the peptide.", "contents": "[Sodium release from tissue paracellular space under the influence of angiotensin II]. Angiotensin II added in vitro in concentration 3-10(-10) M increased the sodium release from the aorta wall, myocardium, and skin in the rat. The action persisted at 2 degrees C and in presence of monoiodacetate. Sodium loading increased the sensitivity of aorta to the action of the angiotensin. The angiotensin-induced sodium release seems to be a step towards the myotropic action of the peptide."} {"id": "PMID:1278542", "title": "[Spectral-correlation analysis of the bioelectrical activity of rabbit brain structures during electrosleep].", "content": "Changes of electric activity of the rabbit cortical and subcortical structures were studied by means of spectrum-correlation analysis during sleep caused by low-frequency stimulation of the supraoptic hypothalamic nucleus. The electrosleep affected the similarity of the electric events in neocortex and subcortical structures. The disturbance of the spatial synchronization is supposed to be due to the activity of nonsynchronized autonomous bioelectric pace-makers in different brain structures.", "contents": "[Spectral-correlation analysis of the bioelectrical activity of rabbit brain structures during electrosleep]. Changes of electric activity of the rabbit cortical and subcortical structures were studied by means of spectrum-correlation analysis during sleep caused by low-frequency stimulation of the supraoptic hypothalamic nucleus. The electrosleep affected the similarity of the electric events in neocortex and subcortical structures. The disturbance of the spatial synchronization is supposed to be due to the activity of nonsynchronized autonomous bioelectric pace-makers in different brain structures."} {"id": "PMID:1278543", "title": "[The role of the posterior hypothalamic nucleus in thyroid hormone secretion during defensive conditioned reflex activity].", "content": "In chronic experiments on adult rabbits, the EEG revealed participation of the posterior hypothalamic nucleus and mediobasal hypothalamus in conditioned avoidance response. Secretion of the thyroid hormone was increased during the response in intact dogs. This reaction of the thyroid gland was maintained for several months. After coagulation of the posterior hypothalamic nucleus the reaction disappeared. This suggests a triggering role of the posterior hypothalamic nucleus in secretion of the thyroid hormone during the avoidance response.", "contents": "[The role of the posterior hypothalamic nucleus in thyroid hormone secretion during defensive conditioned reflex activity]. In chronic experiments on adult rabbits, the EEG revealed participation of the posterior hypothalamic nucleus and mediobasal hypothalamus in conditioned avoidance response. Secretion of the thyroid hormone was increased during the response in intact dogs. This reaction of the thyroid gland was maintained for several months. After coagulation of the posterior hypothalamic nucleus the reaction disappeared. This suggests a triggering role of the posterior hypothalamic nucleus in secretion of the thyroid hormone during the avoidance response."} {"id": "PMID:1278544", "title": "[Transformation of neuronal activity in the cat lateral geniculate body].", "content": "The neuronal activity transformations were studied in the cat LGB under the action of nembutal, light stimulation, and micropolarization of geniculate cells. The transformation of single spike activity into bursts was found to reflect the inhibitory state of the neurons. Their excitation entailed a reverse transformation. Short feed-back connections functioning within the microsystems of LGB neurons are supposed to underlie the transformations.", "contents": "[Transformation of neuronal activity in the cat lateral geniculate body]. The neuronal activity transformations were studied in the cat LGB under the action of nembutal, light stimulation, and micropolarization of geniculate cells. The transformation of single spike activity into bursts was found to reflect the inhibitory state of the neurons. Their excitation entailed a reverse transformation. Short feed-back connections functioning within the microsystems of LGB neurons are supposed to underlie the transformations."} {"id": "PMID:1278545", "title": "[The role of the autonomic nervous system in regulating the hydrodynamics of the intact eye].", "content": "In cats, the low-molecular indicator: radioactive phosphorus, and the tonography revealed that the local application of acetylcholine accelerates the fluid exchange in the intact eye, considerably facilitating the outflow. Noradrenaline and the threshold stimulation of the cervical sympathetic nerve slow down the intraeye fluid exchange, decreasing the outflow. The data obtained suggest that the neural regulation of the eye hydrodynamics involves, mainly, a direct effect of the vegetative innervation on the eye drainage system.", "contents": "[The role of the autonomic nervous system in regulating the hydrodynamics of the intact eye]. In cats, the low-molecular indicator: radioactive phosphorus, and the tonography revealed that the local application of acetylcholine accelerates the fluid exchange in the intact eye, considerably facilitating the outflow. Noradrenaline and the threshold stimulation of the cervical sympathetic nerve slow down the intraeye fluid exchange, decreasing the outflow. The data obtained suggest that the neural regulation of the eye hydrodynamics involves, mainly, a direct effect of the vegetative innervation on the eye drainage system."} {"id": "PMID:1278546", "title": "[Discrimination of the direction of the E-vector of linearly polarized light by the goldfish retina].", "content": "Responses of the goldfish ganglion cells to flashes of linear-polarized light with different positions of the E-vector divided them into on-, off, and on--off types. Change in the E-vector position changed the responses of all three types of the ganglion cells. These ganglion cells register the E-vector position with different degrees of accuracy. Analysis of the responses revealed that the information on the polarization plane position is encoded by the number of spikes of the ganglion cells discharges.", "contents": "[Discrimination of the direction of the E-vector of linearly polarized light by the goldfish retina]. Responses of the goldfish ganglion cells to flashes of linear-polarized light with different positions of the E-vector divided them into on-, off, and on--off types. Change in the E-vector position changed the responses of all three types of the ganglion cells. These ganglion cells register the E-vector position with different degrees of accuracy. Analysis of the responses revealed that the information on the polarization plane position is encoded by the number of spikes of the ganglion cells discharges."} {"id": "PMID:1278547", "title": "[Changes in the functioning of the anticoagulant system of splenectomized animals during immobilization].", "content": "Changes of the anticoagulating system's (ACS) function depend on time elapsing after removal of the spleen, therefore different degrees of ACS activation after 30-min immobilization stress can be observed. In the animals with completely or partially removed spleen, the stress induces activation of the ACS function as expressed by increase in the plasma total fibrinolytic activity, nonfermentative fibrinolysis, decrease in the fibrinogen concentration, activation of the blood plasma anticoagulating function. Hovewer, on the 7th--9th day after removal of the spleen, when the ACS function is thoroughly depressed, the 30-min immobilization stress decreases the plasma anticoagulating activity and, to a certain extent, restricts the appearance of the heparin complex compounds. The latter is due to antagonistic effect of the factor XIII whose activity increases in the blood of the experimental animals. By the 21st day a complete restoration of ACS function occurs in the spleenectomized animals which accounts for the same degree of ACS activation in response to the stress both in the experimental and in control animals.", "contents": "[Changes in the functioning of the anticoagulant system of splenectomized animals during immobilization]. Changes of the anticoagulating system's (ACS) function depend on time elapsing after removal of the spleen, therefore different degrees of ACS activation after 30-min immobilization stress can be observed. In the animals with completely or partially removed spleen, the stress induces activation of the ACS function as expressed by increase in the plasma total fibrinolytic activity, nonfermentative fibrinolysis, decrease in the fibrinogen concentration, activation of the blood plasma anticoagulating function. Hovewer, on the 7th--9th day after removal of the spleen, when the ACS function is thoroughly depressed, the 30-min immobilization stress decreases the plasma anticoagulating activity and, to a certain extent, restricts the appearance of the heparin complex compounds. The latter is due to antagonistic effect of the factor XIII whose activity increases in the blood of the experimental animals. By the 21st day a complete restoration of ACS function occurs in the spleenectomized animals which accounts for the same degree of ACS activation in response to the stress both in the experimental and in control animals."} {"id": "PMID:1278549", "title": "[A new model of the cardio-cardiac reflex].", "content": "A special cardiac vagal afferent stimulation was used in frogs. Bursts of stimuli were applied to the central end of the left cardiac bransh of the vagus with frequency of 1 burst per a heart beat during 2--5 heart beats. In this way the R-wave of the ECG triggered the stimulator after a desired delay. The stimulation induced hypotension and decreased the heart rate, both effects being abolished by cutting the right cardiac branch of the vagus. Every burst of stimuli applied to the left cardiac branch evoked a discharge of the efferent cardiac fibers in the right vagus. Both bradycardia and the energy of the efferent discharges were found to depend on the intensity of stimulation and on the bursts relation to the phases of the cardiac cycle. Maximal cardiac slowing and maximal energy of the efferent vagal discharges were observed when the bursts were synchronized with S--T interval, while minimal those - when the stimulation occurred during T--P interval of the ECG.", "contents": "[A new model of the cardio-cardiac reflex]. A special cardiac vagal afferent stimulation was used in frogs. Bursts of stimuli were applied to the central end of the left cardiac bransh of the vagus with frequency of 1 burst per a heart beat during 2--5 heart beats. In this way the R-wave of the ECG triggered the stimulator after a desired delay. The stimulation induced hypotension and decreased the heart rate, both effects being abolished by cutting the right cardiac branch of the vagus. Every burst of stimuli applied to the left cardiac branch evoked a discharge of the efferent cardiac fibers in the right vagus. Both bradycardia and the energy of the efferent discharges were found to depend on the intensity of stimulation and on the bursts relation to the phases of the cardiac cycle. Maximal cardiac slowing and maximal energy of the efferent vagal discharges were observed when the bursts were synchronized with S--T interval, while minimal those - when the stimulation occurred during T--P interval of the ECG."} {"id": "PMID:1278550", "title": "[Reactions of the volume vessels of skeletal muscles to adrenergic stimulation at different levels of venous pressure].", "content": "In cats, during perfusion of the shank with a constant blood volume and in artificial changing of the venous pressure, the electric stimulation of the lumbal sympathetic chains and administration of noradrenaline in the perfusate were shown to be able to evoke both the constrictory and the dilatory responses of the capacitance vessels against the background of constriction of the resistance vessels. The 10--15 mm Hg venous pressure was optimal for the constrictory responses of the shank capacitance vessels. At the extreme levels of venous pressure (0;5 and 20;25 mm Hg), the relative weight of dilatory responses of the capacitance vessels was increased in the sum total of responses to the used adrenergic effects.", "contents": "[Reactions of the volume vessels of skeletal muscles to adrenergic stimulation at different levels of venous pressure]. In cats, during perfusion of the shank with a constant blood volume and in artificial changing of the venous pressure, the electric stimulation of the lumbal sympathetic chains and administration of noradrenaline in the perfusate were shown to be able to evoke both the constrictory and the dilatory responses of the capacitance vessels against the background of constriction of the resistance vessels. The 10--15 mm Hg venous pressure was optimal for the constrictory responses of the shank capacitance vessels. At the extreme levels of venous pressure (0;5 and 20;25 mm Hg), the relative weight of dilatory responses of the capacitance vessels was increased in the sum total of responses to the used adrenergic effects."} {"id": "PMID:1278551", "title": "[The effect of exogenous adrenaline and angiotensin II on the resistance vessels of the cat kidney].", "content": "In experiments with perfusion of the renal vessels with isotonic saline solution, the ability of angiotensin-II to activate the smooth muscle cells of these vessels was shown: both by direct myotropic action and in an indirect way - by catecholamines. Obvious tachyphylaxis is characteristic only for the direct myotropic effect of angiotensin-II. The data obtained suggest that the direct effect of angiotensin-II is selective for certain intrarenal vessels, while indirect action is more universal.", "contents": "[The effect of exogenous adrenaline and angiotensin II on the resistance vessels of the cat kidney]. In experiments with perfusion of the renal vessels with isotonic saline solution, the ability of angiotensin-II to activate the smooth muscle cells of these vessels was shown: both by direct myotropic action and in an indirect way - by catecholamines. Obvious tachyphylaxis is characteristic only for the direct myotropic effect of angiotensin-II. The data obtained suggest that the direct effect of angiotensin-II is selective for certain intrarenal vessels, while indirect action is more universal."} {"id": "PMID:1278552", "title": "[Changes in intracranial pressure and impedance in the presence of air and gad embolism].", "content": "In biophysical models and in acute experiments on animals, the air was administered in measured volumes into the artificial blood flow and into the common carotid artery in dogs. When air bubbles get into the electric field between electrodes, specific changes of impedance depending on the bubbles size could be recorded. A lot of small bubbles sharply increased the impedance according to their total volume. Ih the air compression up to 10 kgs/cm2 and in following decompression, the intracranial impedance and pressure smoothly changed according to barogram. After 15 min of stying under pressure the dogs developed during decompression a sharp increase of the intracranial impedance and pressure which, similarly to the results of the model experiments, should be regarded as the consequence of formation of a free gas phase in the system of intracranial circulation.", "contents": "[Changes in intracranial pressure and impedance in the presence of air and gad embolism]. In biophysical models and in acute experiments on animals, the air was administered in measured volumes into the artificial blood flow and into the common carotid artery in dogs. When air bubbles get into the electric field between electrodes, specific changes of impedance depending on the bubbles size could be recorded. A lot of small bubbles sharply increased the impedance according to their total volume. Ih the air compression up to 10 kgs/cm2 and in following decompression, the intracranial impedance and pressure smoothly changed according to barogram. After 15 min of stying under pressure the dogs developed during decompression a sharp increase of the intracranial impedance and pressure which, similarly to the results of the model experiments, should be regarded as the consequence of formation of a free gas phase in the system of intracranial circulation."} {"id": "PMID:1278553", "title": "[The pressor reflex induced by skeletal muscle contraction and its influence on the reflex from the sino-aortic zones].", "content": "The cardiovascular response to 10 sec tetanic muscular contractions was studied in the decerebrated cat. A pressor reflex about 30 mm Hg occurred during hindlimb contractions evoked by ventral roots (L6, L7, S1) stimulation. The pressor reflex was associated with a decrease of blood flow in working and resting muscles and a minimal changes of heart rate and left ventricular contractility. An increase of systemic resistance, as a main cause of pressor reflex is suggested. Static contractions of muscles and stimulation of muscle nerve evoked stronger inhibition of baroreflex than cutaneous nerve stimulation of nociceptive stimuli. Inhibition of the cardiac component of baroreflex during muscular exercise was shown.", "contents": "[The pressor reflex induced by skeletal muscle contraction and its influence on the reflex from the sino-aortic zones]. The cardiovascular response to 10 sec tetanic muscular contractions was studied in the decerebrated cat. A pressor reflex about 30 mm Hg occurred during hindlimb contractions evoked by ventral roots (L6, L7, S1) stimulation. The pressor reflex was associated with a decrease of blood flow in working and resting muscles and a minimal changes of heart rate and left ventricular contractility. An increase of systemic resistance, as a main cause of pressor reflex is suggested. Static contractions of muscles and stimulation of muscle nerve evoked stronger inhibition of baroreflex than cutaneous nerve stimulation of nociceptive stimuli. Inhibition of the cardiac component of baroreflex during muscular exercise was shown."} {"id": "PMID:1278556", "title": "[The dynamics of changes in oxygen tension, circulatory rats, muscular and rectal temperatures in dinitrophenol hyperthermia].", "content": "In rabbits, i. v. administration of 2,4-dinitrophenol (20 mg/kg) rapidly increases the temperature and the blood flow speed, simultaneously decreasing the oxygen available, in the skeletal muscle. The muscular and rectal temperatures go on raising up to the maximum till about 90th min and then slowly decrease. The blood flow speed starts rapidly to decrease after the 5th-6th min, while oxygen available starts to increase fradually by the end of the 1st hour. The data obtained are related to the mechanism of increase in the peripheral heat production.", "contents": "[The dynamics of changes in oxygen tension, circulatory rats, muscular and rectal temperatures in dinitrophenol hyperthermia]. In rabbits, i. v. administration of 2,4-dinitrophenol (20 mg/kg) rapidly increases the temperature and the blood flow speed, simultaneously decreasing the oxygen available, in the skeletal muscle. The muscular and rectal temperatures go on raising up to the maximum till about 90th min and then slowly decrease. The blood flow speed starts rapidly to decrease after the 5th-6th min, while oxygen available starts to increase fradually by the end of the 1st hour. The data obtained are related to the mechanism of increase in the peripheral heat production."} {"id": "PMID:1278557", "title": "[Several statistical patterns in the control of vascular thermoregulatory reactions].", "content": "In intact rabbits, in near to natural conditions with ambient temperature changing from 15 to 40 degrees C, switching on (off) of the thermoregulatory vascular response in the ear occurs at the moments when the suspended temperature of the hypothalamus, the temperature of the back skin, and speed of changes in the skin temperature attain (drop to) some extreme value. Quantitative estimates of the weight for this summation, were obtained.", "contents": "[Several statistical patterns in the control of vascular thermoregulatory reactions]. In intact rabbits, in near to natural conditions with ambient temperature changing from 15 to 40 degrees C, switching on (off) of the thermoregulatory vascular response in the ear occurs at the moments when the suspended temperature of the hypothalamus, the temperature of the back skin, and speed of changes in the skin temperature attain (drop to) some extreme value. Quantitative estimates of the weight for this summation, were obtained."} {"id": "PMID:1278558", "title": "[The role of renal beta-adrenoreceptors in regulating its blood supply and urine formation].", "content": "The dog kidney blood flow and filtrative and reabsorptive functions were studied with the aid of electromagnetic flowmeter and endogenic creatinine. Beta-adrenostimulation with izadrine caused dilatation of the kidney vessels. Beta-adrenoblockade led to the opposite though insignificant effect. Beta-adrenostimulation in intact animals entailed systemic hypotension, activation of the kidney blood flow and reabsorption, decrease of filtration and diuresis. Following stabilization of arterial pressure or central inhibition of vasopressin, the beta-adrenostimulation led to the decrease in reabsorption. The data obtained seem to indicate that the direct effect of beta-adrenostimulation of the kidney channels is manifested by the inhibition of reabsorption.", "contents": "[The role of renal beta-adrenoreceptors in regulating its blood supply and urine formation]. The dog kidney blood flow and filtrative and reabsorptive functions were studied with the aid of electromagnetic flowmeter and endogenic creatinine. Beta-adrenostimulation with izadrine caused dilatation of the kidney vessels. Beta-adrenoblockade led to the opposite though insignificant effect. Beta-adrenostimulation in intact animals entailed systemic hypotension, activation of the kidney blood flow and reabsorption, decrease of filtration and diuresis. Following stabilization of arterial pressure or central inhibition of vasopressin, the beta-adrenostimulation led to the decrease in reabsorption. The data obtained seem to indicate that the direct effect of beta-adrenostimulation of the kidney channels is manifested by the inhibition of reabsorption."} {"id": "PMID:1278566", "title": "The blocking effect of conditioned media from tumour cell cultures on the lysis of target cells by immune lymphocytes and macrophages.", "content": "Conditioned media prepared from tumour cell cultures of three mouse strains and man blocked the lytic reaction of target cells by allogeneic immune lymphocytes and macrophages. No effect was exerted on this reaction; when conditioned media prepared from non-tumour cell cultures were utilized. The lytic reaction was even enhanced in some cases. It is suggested that tumour cells cultured in vitro release into culture media substances which may inhibit the lysis of target cells by lymphocytes and macrophages.", "contents": "The blocking effect of conditioned media from tumour cell cultures on the lysis of target cells by immune lymphocytes and macrophages. Conditioned media prepared from tumour cell cultures of three mouse strains and man blocked the lytic reaction of target cells by allogeneic immune lymphocytes and macrophages. No effect was exerted on this reaction; when conditioned media prepared from non-tumour cell cultures were utilized. The lytic reaction was even enhanced in some cases. It is suggested that tumour cells cultured in vitro release into culture media substances which may inhibit the lysis of target cells by lymphocytes and macrophages."} {"id": "PMID:1278567", "title": "Cytological and histological changes in the spleen of continuously irradiated rats.", "content": "The study evaluates quantitative cytological and histological changes in spleen white and red pulp of rats continuously irradiated for up to 140 days with daily dose rates ranging from 0.5R--82.5R. Significant reduction of lymphocyte incidence begins at the rate of 5R/day and the decrease deepens with the rising dose rate until a steady state around 5 per cent is reached at 82.5R/day. Small lymphocytes are relatively more affected. Irradiated animals show a wave-like rising of ectopic erythropoiesis in spleen red pulp from day 30 on even with the lowest dose rates of 0.5R and 1R/day. The ratio or relative incidences of haemocytoblasts to erythroblasts increases approximately twofold, indicating that a substantial reduction of stem cells is compensated to a large extent already at an early stage of erythropoiesis. Beginning with the 40th day of exposure, the incidence of myeloid elements also rises, the increase being more apparent at medium-range dose rates for eosinophils than neutrophils. Both the red and white spleen pulps of exposed animals display an increased incidence of plasma cells.", "contents": "Cytological and histological changes in the spleen of continuously irradiated rats. The study evaluates quantitative cytological and histological changes in spleen white and red pulp of rats continuously irradiated for up to 140 days with daily dose rates ranging from 0.5R--82.5R. Significant reduction of lymphocyte incidence begins at the rate of 5R/day and the decrease deepens with the rising dose rate until a steady state around 5 per cent is reached at 82.5R/day. Small lymphocytes are relatively more affected. Irradiated animals show a wave-like rising of ectopic erythropoiesis in spleen red pulp from day 30 on even with the lowest dose rates of 0.5R and 1R/day. The ratio or relative incidences of haemocytoblasts to erythroblasts increases approximately twofold, indicating that a substantial reduction of stem cells is compensated to a large extent already at an early stage of erythropoiesis. Beginning with the 40th day of exposure, the incidence of myeloid elements also rises, the increase being more apparent at medium-range dose rates for eosinophils than neutrophils. Both the red and white spleen pulps of exposed animals display an increased incidence of plasma cells."} {"id": "PMID:1278568", "title": "Heterokaryosis in Trichophyton mentagrophytes.", "content": "Heterokaryosis was demonstrated in the dermatophyte Trichophyton mentagrophytes. Ten biochemical mutants of this fungus, requiring, tryptophan, histidine, methionine, arginine and thiamine, were used in the experiments. Six mutant pairs with different biochemical markers formed the heterokaryotic mycelium (trp + his, trp + met arg, trp + thi, his + met arg). The heterokaryotic constitution was determined by ths dissociation of a heterokaryon into auxotrophic components in microconidial spreads and by the isolation of the hyphal tips from which the prototrophic colonies grew out. The heterokaryotic constitution was expressed by the complementation of nutritional requirements and morphologically.", "contents": "Heterokaryosis in Trichophyton mentagrophytes. Heterokaryosis was demonstrated in the dermatophyte Trichophyton mentagrophytes. Ten biochemical mutants of this fungus, requiring, tryptophan, histidine, methionine, arginine and thiamine, were used in the experiments. Six mutant pairs with different biochemical markers formed the heterokaryotic mycelium (trp + his, trp + met arg, trp + thi, his + met arg). The heterokaryotic constitution was determined by ths dissociation of a heterokaryon into auxotrophic components in microconidial spreads and by the isolation of the hyphal tips from which the prototrophic colonies grew out. The heterokaryotic constitution was expressed by the complementation of nutritional requirements and morphologically."} {"id": "PMID:1278569", "title": "Independent cyclic fluctuations of cell surface parameters: expression of H-2 antigens, rosetting capacity and thickness of the cell coat.", "content": "Cultures of a mouse X mouse cell hybrid (synchronized either by hydroxyurea or Colcemid) were tested for fluctuations during the cell cycle of several parameters characterizing the cell surface: expression of H-2 antigens, capacity of the cells to form rosettes with sheep red blood cells and thickness of the cell coat. H-2 antigenicity of cells collected at different phases of the mitotic cycle was assessed on the basis of their capacity to bind 125I-labelled antibodies as well as their sensitivity to complement dependent immune lysis. The latter parameters fluctuated more or less independently: around mitosis, their trends were even opposite and minimum antibody-binding capacity roughly coincided with maximum cytolytic sensitivity. The cyclic fluctuations of H-2 antigenicity were similar, but not identical for two antigens contributed to the cell hybrid by different parents and even the curves for two antigens of the same parental origin displayed a slight shift one from another. The frequency of cells forming large rosettes (i.e., of more than six SRBC) reached its peak roughly at the boundery of G1 and S phase. Mitotic (versus non-mitotic) cells had a significantly thicker cell coat (as visualized by ruthenium red staining and electron microscopy) and a high incidence of morphological abnormalities. The tested parameters thus seem to fluctuate independently of each other.", "contents": "Independent cyclic fluctuations of cell surface parameters: expression of H-2 antigens, rosetting capacity and thickness of the cell coat. Cultures of a mouse X mouse cell hybrid (synchronized either by hydroxyurea or Colcemid) were tested for fluctuations during the cell cycle of several parameters characterizing the cell surface: expression of H-2 antigens, capacity of the cells to form rosettes with sheep red blood cells and thickness of the cell coat. H-2 antigenicity of cells collected at different phases of the mitotic cycle was assessed on the basis of their capacity to bind 125I-labelled antibodies as well as their sensitivity to complement dependent immune lysis. The latter parameters fluctuated more or less independently: around mitosis, their trends were even opposite and minimum antibody-binding capacity roughly coincided with maximum cytolytic sensitivity. The cyclic fluctuations of H-2 antigenicity were similar, but not identical for two antigens contributed to the cell hybrid by different parents and even the curves for two antigens of the same parental origin displayed a slight shift one from another. The frequency of cells forming large rosettes (i.e., of more than six SRBC) reached its peak roughly at the boundery of G1 and S phase. Mitotic (versus non-mitotic) cells had a significantly thicker cell coat (as visualized by ruthenium red staining and electron microscopy) and a high incidence of morphological abnormalities. The tested parameters thus seem to fluctuate independently of each other."} {"id": "PMID:1278570", "title": "H-2 associated differences in the weight of some androgen influenced organs in (C57BL/10ScSnPh X AKR/J) F2 individuals.", "content": "We have followed the possible influence of H-2 system on the differences in the relative weights of testes, vesicular gland and thymus in animals of a segregating (B10 X AKR) F2 generation. H-2b/H-2b male mice had significantly higher values of relative vesicular gland weight and significantly lower values of relative testes weight than H-2k/H-2k males. No differences in the relative thymus weight were found between these two groups of animals. The differences are caused by a complex effect of the H.2 associated genetic factor(s) because they influence simultaneously the body weight and the organ weights, the two indicators being mutually dependent to some extent.", "contents": "H-2 associated differences in the weight of some androgen influenced organs in (C57BL/10ScSnPh X AKR/J) F2 individuals. We have followed the possible influence of H-2 system on the differences in the relative weights of testes, vesicular gland and thymus in animals of a segregating (B10 X AKR) F2 generation. H-2b/H-2b male mice had significantly higher values of relative vesicular gland weight and significantly lower values of relative testes weight than H-2k/H-2k males. No differences in the relative thymus weight were found between these two groups of animals. The differences are caused by a complex effect of the H.2 associated genetic factor(s) because they influence simultaneously the body weight and the organ weights, the two indicators being mutually dependent to some extent."} {"id": "PMID:1278577", "title": "The continuation of education after marriage among women in the United States: 1970.", "content": "Data from the 1970 National Fertility Study are used to assess the extent and determinants of post-nuptial education among women in the United States. Over one-fifth of all women have attended high school or college since marriage; over one-third either have returned to school or anticipate returning to an academic institution sometime in the future. This phenomenon is apparently increasing since women married less than five years have already attended school in as great a proportion as women married 15-19 years. Examination of differentials reveals for both blacks and whites that post-nupital education is higher among women who: (1) attended college before marriage, (2) married early, (3) are currently separated or divorced, (4) support egalitarian sex-role attitudes, or (5) whose most recent occupation is in the professional, managerial, or administrative category. Post-nuptial trends in education undoubtedly reflect the much broader social phenomenon of changing sex-role perceptions.", "contents": "The continuation of education after marriage among women in the United States: 1970. Data from the 1970 National Fertility Study are used to assess the extent and determinants of post-nuptial education among women in the United States. Over one-fifth of all women have attended high school or college since marriage; over one-third either have returned to school or anticipate returning to an academic institution sometime in the future. This phenomenon is apparently increasing since women married less than five years have already attended school in as great a proportion as women married 15-19 years. Examination of differentials reveals for both blacks and whites that post-nupital education is higher among women who: (1) attended college before marriage, (2) married early, (3) are currently separated or divorced, (4) support egalitarian sex-role attitudes, or (5) whose most recent occupation is in the professional, managerial, or administrative category. Post-nuptial trends in education undoubtedly reflect the much broader social phenomenon of changing sex-role perceptions."} {"id": "PMID:1278578", "title": "Family size in successive generations: the effects of birth order, intergenerational change in lifestyle, and familial satisfaction.", "content": "Studies of family size in successive generations have found a small but persistently positive effect of size of family of orientation. Recent work has suggested that this relationship may be influenced by birth order, intergenerational change in lifestyle, and familial satisfaction. Data from a 24-year longitudinal study of women in Pennsylvania indicate that number of siblings does influence size of family of procreation. More important, this relationship is stronger among women who were first-born that later-born, stronger for those not experiencing intergenerational change than for those who changed, and stronger among those who at age 16 were satisfied with their parental family than for those who were dissatisfied.", "contents": "Family size in successive generations: the effects of birth order, intergenerational change in lifestyle, and familial satisfaction. Studies of family size in successive generations have found a small but persistently positive effect of size of family of orientation. Recent work has suggested that this relationship may be influenced by birth order, intergenerational change in lifestyle, and familial satisfaction. Data from a 24-year longitudinal study of women in Pennsylvania indicate that number of siblings does influence size of family of procreation. More important, this relationship is stronger among women who were first-born that later-born, stronger for those not experiencing intergenerational change than for those who changed, and stronger among those who at age 16 were satisfied with their parental family than for those who were dissatisfied."} {"id": "PMID:1278579", "title": "An analysis of the impact of education on family size.", "content": "The impact of education on family size is divided into a direct effect (holding labor force participation and age at marriage constant) and an indirect effect (varying labor force participation and age at marriage). The results suggest that (1) the indirect effect of education is greater at higher levels of the wife's education, (2) the direct effect is greater at lower levels of education in most cases, (3) the indirect effects do not vary systematically with husband's education, (4) but the direct effect does vary systematically with husband's education if the education of the wife is low but not if wife's education is high.", "contents": "An analysis of the impact of education on family size. The impact of education on family size is divided into a direct effect (holding labor force participation and age at marriage constant) and an indirect effect (varying labor force participation and age at marriage). The results suggest that (1) the indirect effect of education is greater at higher levels of the wife's education, (2) the direct effect is greater at lower levels of education in most cases, (3) the indirect effects do not vary systematically with husband's education, (4) but the direct effect does vary systematically with husband's education if the education of the wife is low but not if wife's education is high."} {"id": "PMID:1278580", "title": "A comparison between Northern and Southern blacks residing in the North.", "content": "Differences between Southern and non-Southern blacks living in the North and West are considered for a wide variety of attributes such as employment, occupation, income, marital stability, and offspring's performance in school. Migrant blacks have generally more favorable rates than their Northern- and Western-born compatriots after standard domographic controls are applied to an unusually detailed set of cross-tabulations based on the One-Percent Sample Tapes for 1960. Perhaps the sharpest gap exists with respect to marital conditions; Southern blacks of both sexes are more likely to marry and, among those ever married, live more frequently with their spouses. Some of the results reported by earlier investigators require considerable modification; For example, the fact that Northern black men are less often at work than migrants has led to speculations about regional differences in work orientation among blacks, but a detailed analysis of labor force activity indicates this pattern does not hold for women. Likewise, the migrant income advantage is found to vary by education such that it is confined to those with low educational attainment. The use of sample tapes permits a novel analysis of differences between Northern-born blacks classified by whether they are second or at least third generation residents of the North (children of Southern- or Northern-born parents, respectively). For the attribute measured, school performance, the gap is essentially nil. Finally, an alternative is suggested to the existing causal interpretations of North-South gaps among black residents of the North. Reconsidered in particular are the higher labor force rates of migrant men and their more frequent employment in blue collar jobs;", "contents": "A comparison between Northern and Southern blacks residing in the North. Differences between Southern and non-Southern blacks living in the North and West are considered for a wide variety of attributes such as employment, occupation, income, marital stability, and offspring's performance in school. Migrant blacks have generally more favorable rates than their Northern- and Western-born compatriots after standard domographic controls are applied to an unusually detailed set of cross-tabulations based on the One-Percent Sample Tapes for 1960. Perhaps the sharpest gap exists with respect to marital conditions; Southern blacks of both sexes are more likely to marry and, among those ever married, live more frequently with their spouses. Some of the results reported by earlier investigators require considerable modification; For example, the fact that Northern black men are less often at work than migrants has led to speculations about regional differences in work orientation among blacks, but a detailed analysis of labor force activity indicates this pattern does not hold for women. Likewise, the migrant income advantage is found to vary by education such that it is confined to those with low educational attainment. The use of sample tapes permits a novel analysis of differences between Northern-born blacks classified by whether they are second or at least third generation residents of the North (children of Southern- or Northern-born parents, respectively). For the attribute measured, school performance, the gap is essentially nil. Finally, an alternative is suggested to the existing causal interpretations of North-South gaps among black residents of the North. Reconsidered in particular are the higher labor force rates of migrant men and their more frequent employment in blue collar jobs;"} {"id": "PMID:1278581", "title": "A refined estimator of measures of location of the age at first marriage.", "content": "Because of bias of unknown sign and extent introduced by age misreporting when calculating the singulate mean age of marriage in the usual manner, Van de Walle has suggested a fairly robust estimator based on stable population structure. Unfortunately not much is known about the properties of this estimator. Various demographers have argued informally that it indeed estimates the SMAM; others feel that it instead estimates the mean age of marriage in a cohort, the mean age of marriage in the stable population, or the singulate median age of marriage. In this paper the properties of this estimator are examined. Further, extensions of the Van de Walle estimator based on regression are shown to be significantly superior to the estimator alone.", "contents": "A refined estimator of measures of location of the age at first marriage. Because of bias of unknown sign and extent introduced by age misreporting when calculating the singulate mean age of marriage in the usual manner, Van de Walle has suggested a fairly robust estimator based on stable population structure. Unfortunately not much is known about the properties of this estimator. Various demographers have argued informally that it indeed estimates the SMAM; others feel that it instead estimates the mean age of marriage in a cohort, the mean age of marriage in the stable population, or the singulate median age of marriage. In this paper the properties of this estimator are examined. Further, extensions of the Van de Walle estimator based on regression are shown to be significantly superior to the estimator alone."} {"id": "PMID:1278582", "title": "Annual fertility rates from Census data on own children: comparisons with vital statistics data for the United States.", "content": "This paper begins by describing the procedure and data requirements for calculating annual fertility rates from census data on own children. Then, using data from the United States Censuses of 1960 and 1970, fully adjusted estimates are presented and compared with recorded vital statistics rates. Total fertility estimates derived from own children data for whites average less than two percent lower than the recorded rates- a difference that can be attributed partially to the fact that the estimates are adjusted for net census undercount but the recorded rates are not. Even without adjustments for mortality, children not living with their mothers, and net census undercount, the own children data estimates accurately replicate recorded trends (even though the levels are misspecified). The utility of own children data for the study of differential fertility is discussed.", "contents": "Annual fertility rates from Census data on own children: comparisons with vital statistics data for the United States. This paper begins by describing the procedure and data requirements for calculating annual fertility rates from census data on own children. Then, using data from the United States Censuses of 1960 and 1970, fully adjusted estimates are presented and compared with recorded vital statistics rates. Total fertility estimates derived from own children data for whites average less than two percent lower than the recorded rates- a difference that can be attributed partially to the fact that the estimates are adjusted for net census undercount but the recorded rates are not. Even without adjustments for mortality, children not living with their mothers, and net census undercount, the own children data estimates accurately replicate recorded trends (even though the levels are misspecified). The utility of own children data for the study of differential fertility is discussed."} {"id": "PMID:1278583", "title": "Effect of adjustment for sex composition in the measurement of fertility on intrinsic rates.", "content": "The inconsistencies inherent in the one-sex models created a need for the construction of what are known as marriage functions, especially for the measurement of fertility. But attempts to develop marriage functions have been frustrated by the inability of the proposed functions to meet certain consistency conditions and also by difficulties in empiracally determining function parameters. Among several functions proposed so far, Das Gupta's (1972) \"effective population\" deserves special mention. He uses both sexes in its formulation, and has shown that the constancy of fertility rates based on such a function together with the constancy of survivorship probabilities of both sexes would result in a stable population. It is suggested in this article that the major source of the problem in a two-sex model seems to be the requirement that the model has to be specific both for sex and age. The ideal of incorporating the relative composition of one sex in the age-specific rates of the other, thereby creating a function dependent on both sexes, is advanced in this article. Such functions, defined explicitly for births, can be easily translated into age-specific birth rates. In addition to simplicity in the definition and form, the conditions leading toward stability can also be established. Interestingly enough, the intrinsic rate for this two-sex model lies in the interval determined by the rates obtained from the two one-sex models.", "contents": "Effect of adjustment for sex composition in the measurement of fertility on intrinsic rates. The inconsistencies inherent in the one-sex models created a need for the construction of what are known as marriage functions, especially for the measurement of fertility. But attempts to develop marriage functions have been frustrated by the inability of the proposed functions to meet certain consistency conditions and also by difficulties in empiracally determining function parameters. Among several functions proposed so far, Das Gupta's (1972) \"effective population\" deserves special mention. He uses both sexes in its formulation, and has shown that the constancy of fertility rates based on such a function together with the constancy of survivorship probabilities of both sexes would result in a stable population. It is suggested in this article that the major source of the problem in a two-sex model seems to be the requirement that the model has to be specific both for sex and age. The ideal of incorporating the relative composition of one sex in the age-specific rates of the other, thereby creating a function dependent on both sexes, is advanced in this article. Such functions, defined explicitly for births, can be easily translated into age-specific birth rates. In addition to simplicity in the definition and form, the conditions leading toward stability can also be established. Interestingly enough, the intrinsic rate for this two-sex model lies in the interval determined by the rates obtained from the two one-sex models."} {"id": "PMID:1278584", "title": "A technique for estimating life expectancy with crude vital rates.", "content": "This paper describes a method of estimating life expectancy at birth on the basis of crude vital rates. The method is derived from stable population theory and it furnishes good estimates insofar as the current crude vital rates of a population are close to its intrinsic rates. This condition is generally met in closed populations which have not experienced sharp movements in fertility. The method is useful for estimating life expectancy in developing nations with good sample registration systems but for which information on age is of poor quality. It is also useful for estimating the movement of life expectancy in certain European nations in the period prior to regular census taking. There are a number of nations and regions in Europe for which long series of birth and death rates are available but for which census age counts are widely spaced.", "contents": "A technique for estimating life expectancy with crude vital rates. This paper describes a method of estimating life expectancy at birth on the basis of crude vital rates. The method is derived from stable population theory and it furnishes good estimates insofar as the current crude vital rates of a population are close to its intrinsic rates. This condition is generally met in closed populations which have not experienced sharp movements in fertility. The method is useful for estimating life expectancy in developing nations with good sample registration systems but for which information on age is of poor quality. It is also useful for estimating the movement of life expectancy in certain European nations in the period prior to regular census taking. There are a number of nations and regions in Europe for which long series of birth and death rates are available but for which census age counts are widely spaced."} {"id": "PMID:1278585", "title": "Some sources of error and their effect on Census statistics.", "content": "Often the reliability of survey data is examined only in relationship to sampling variances, excluding many other potential sources of error. If the sampling variance dominates the mean-square error, then few mistakes result by considering sampling variance only; however, if sampling variance is only a small part of the mean-square error, serious mistakes in inference could be made. The Bureau of the Census has developed a model describing the joint effect of sampling and nonsampling errors on census statistics. This article shows how a study of the components of error may lead to methods of improving the accuracy and reliability of survey data.", "contents": "Some sources of error and their effect on Census statistics. Often the reliability of survey data is examined only in relationship to sampling variances, excluding many other potential sources of error. If the sampling variance dominates the mean-square error, then few mistakes result by considering sampling variance only; however, if sampling variance is only a small part of the mean-square error, serious mistakes in inference could be made. The Bureau of the Census has developed a model describing the joint effect of sampling and nonsampling errors on census statistics. This article shows how a study of the components of error may lead to methods of improving the accuracy and reliability of survey data."} {"id": "PMID:1278601", "title": "Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast.", "content": "A protein-sparing modified fast (PSMF), which is a total fast modified by the intake of 1.2-1.4 gm. protein per kilogram ideal body weight (IBW), fluids ad libitum, and vitamin and mineral supplementation, allows effective control of carbohydrate metabolism and hunger. It reduces serum glucose and insulin concentrations in obese diabetic patients and increases free fatty acid and ketone body concentrations; ketonuria appears within 24-72 hours. When this fast was applied to seven obese adult-onset diabetics who were receiving 30-100 units of insulin per day, insulin could be discontinued after 0-19 days (mean, 6.5). In the three patients who had extensive nitrogen-balance studies, balance could be maintained chronically by 1.3 gm. protein per kilogram IBW, despite the gross caloric inadequacy of the diet. The PSMF was tolerated well in an outpatient setting after the initial insulin-withdrawal phase had occurred in the hospital. Significant improvements in blood pressure, lipid abnormalities, parameters of carbohydrate metabolism, and cardiorespiratory, symptoms were associated with weight loss and/or the PSMF. For diabetics with some endogenous insulin reserve, the PSMF offers significant advantages for weight reduction, including preservation of lean body mass (as reflected in nitrogen balance) and withdrawal of exogenous insulin.", "contents": "Nitrogen metabolism and insulin requirements in obese diabetic adults on a protein-sparing modified fast. A protein-sparing modified fast (PSMF), which is a total fast modified by the intake of 1.2-1.4 gm. protein per kilogram ideal body weight (IBW), fluids ad libitum, and vitamin and mineral supplementation, allows effective control of carbohydrate metabolism and hunger. It reduces serum glucose and insulin concentrations in obese diabetic patients and increases free fatty acid and ketone body concentrations; ketonuria appears within 24-72 hours. When this fast was applied to seven obese adult-onset diabetics who were receiving 30-100 units of insulin per day, insulin could be discontinued after 0-19 days (mean, 6.5). In the three patients who had extensive nitrogen-balance studies, balance could be maintained chronically by 1.3 gm. protein per kilogram IBW, despite the gross caloric inadequacy of the diet. The PSMF was tolerated well in an outpatient setting after the initial insulin-withdrawal phase had occurred in the hospital. Significant improvements in blood pressure, lipid abnormalities, parameters of carbohydrate metabolism, and cardiorespiratory, symptoms were associated with weight loss and/or the PSMF. For diabetics with some endogenous insulin reserve, the PSMF offers significant advantages for weight reduction, including preservation of lean body mass (as reflected in nitrogen balance) and withdrawal of exogenous insulin."} {"id": "PMID:1278602", "title": "Insulin and free fatty acid levels during oral glucose tolerance tests and their relation to age in 70 healthy children.", "content": "In 70 healthy children aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acids were measured during a three-hour glucose tolerance test. The results are presented for the whole group as well as for three age groups: three months-five years, six-10 years, and 11-15 years. It is demonstrated that (1) glucose levels are significantly lower in young children (younger than five years); (2) there are no significant age-related changes in free fatty acid concentration; (3) insulin levels are increasing constantly and significantly with age, the most strikingly at the age of onset of puberty; the absence of notable changes in glucose tolerance results in a rise of the I/G ratio as well. The causes for the increase of insulin secretion with age, whether of peripheral or pancreatic order, are still speculative.", "contents": "Insulin and free fatty acid levels during oral glucose tolerance tests and their relation to age in 70 healthy children. In 70 healthy children aged from three months to 15 years, blood glucose, immunoreactive insulin, and free fatty acids were measured during a three-hour glucose tolerance test. The results are presented for the whole group as well as for three age groups: three months-five years, six-10 years, and 11-15 years. It is demonstrated that (1) glucose levels are significantly lower in young children (younger than five years); (2) there are no significant age-related changes in free fatty acid concentration; (3) insulin levels are increasing constantly and significantly with age, the most strikingly at the age of onset of puberty; the absence of notable changes in glucose tolerance results in a rise of the I/G ratio as well. The causes for the increase of insulin secretion with age, whether of peripheral or pancreatic order, are still speculative."} {"id": "PMID:1278603", "title": "Diabetes mellitus in American Indians - standards for diagnosis and management.", "content": "In most American Indian tribes the frequency of diabetes mellitus is much greater than among the non-Indians, and surveillance of health records has shown that many types of illnesses occur more often in the diabetics than in the nondiabetics. Standards, or guidelines, have been developed for diabetes detection and treatment for purposes of limiting diabetes diagnoses to persons with high probabilities of having the disease and concentrating diabetes case finding among high-risk groups or individuals. The guidelines emphasize that early diagnosis and careful management of diabetic pregnancies can decrease rates of macrosomia, congenital malforamtions, spontaneous abortion, stillbirth, and neonatal death. Diabetes management is based on staging criteria and requires trained paramedical workers in many aspects of management of asymptomatic diabetics, while the physicians concentrate more extensively on diabetes with symptoms and remediable complications.", "contents": "Diabetes mellitus in American Indians - standards for diagnosis and management. In most American Indian tribes the frequency of diabetes mellitus is much greater than among the non-Indians, and surveillance of health records has shown that many types of illnesses occur more often in the diabetics than in the nondiabetics. Standards, or guidelines, have been developed for diabetes detection and treatment for purposes of limiting diabetes diagnoses to persons with high probabilities of having the disease and concentrating diabetes case finding among high-risk groups or individuals. The guidelines emphasize that early diagnosis and careful management of diabetic pregnancies can decrease rates of macrosomia, congenital malforamtions, spontaneous abortion, stillbirth, and neonatal death. Diabetes management is based on staging criteria and requires trained paramedical workers in many aspects of management of asymptomatic diabetics, while the physicians concentrate more extensively on diabetes with symptoms and remediable complications."} {"id": "PMID:1278604", "title": "Human maternal and fetal serum insulin and growth hormone (HGH) response to glucose and leucine.", "content": "Maternal and fetal serum insulin and HGH responses to glucose, leucine, and glucose plus leucine were examined by infusions to pregnant women at term immediately before cesarean section. Leucine (15 gm.) with glucose (50 gm.) administered for 30 minutes to the mothers stimulates markedly maternal and fetal insulin secretion while infusion of glucose (50 gm.) causes a lower insulin response. When infusing glucose alone we noted that the duration rather than the degree of hyperglycemia determined the fetal insulin response. In fact, when glucose is given to the mother for 60 minutes the fetal insulin response is higher than when the same dose is infused for 30 minutes. Maternal infusion of leucine (15 gm.) for 30 minutes elicits only a very slight increase of insulin secretion in the mother and no change in the fetus. None of the infusions causes any alteration whatsoever in either maternal or fetal HGH secretion.", "contents": "Human maternal and fetal serum insulin and growth hormone (HGH) response to glucose and leucine. Maternal and fetal serum insulin and HGH responses to glucose, leucine, and glucose plus leucine were examined by infusions to pregnant women at term immediately before cesarean section. Leucine (15 gm.) with glucose (50 gm.) administered for 30 minutes to the mothers stimulates markedly maternal and fetal insulin secretion while infusion of glucose (50 gm.) causes a lower insulin response. When infusing glucose alone we noted that the duration rather than the degree of hyperglycemia determined the fetal insulin response. In fact, when glucose is given to the mother for 60 minutes the fetal insulin response is higher than when the same dose is infused for 30 minutes. Maternal infusion of leucine (15 gm.) for 30 minutes elicits only a very slight increase of insulin secretion in the mother and no change in the fetus. None of the infusions causes any alteration whatsoever in either maternal or fetal HGH secretion."} {"id": "PMID:1278605", "title": "Effect of somatostatin on blood sugar, plasma growth hormone, and glucagon levels in diabetic children.", "content": "In nine children with clinically overt insulin-dependent diabetes mellitus the authors injected cyclic somatostatin (3 mug./kg. bolus, followed by infusion of 13 mug./kg. in 60 minutes) and measured blood glucose, plasma growth hormone, and glucagon concentrations throughout the infusion. The rapid administration produced no significant changes of these parameters. With the prolonged infusion there was a significant reduction of blood glucose from a mean of 148 +/- 19.7 to a mean of 88.5 +/- 18.1 mg./100 ml. (P less than 0.005) and of plasma glucagon from a basal mean of 33.3 +/- 2.4 to a minimum mean of 22.1 +/- 1.7 pg./ml. (P less than 0.01). There was a statistically significant correlation between the two parameters (0.01 less than P less than 0.05). Plasma GH values also diminished during the infusion, but the reduction was not statistically significant. These results show that somatostatin lowers blood glucose concentrations as a secondary effect of inhibition of glucagon secretion. Somatostatin is not suitable for therapy in diabetes. We speculate that a similar substance with a more prolonged and specific action on glucagon might prove of practical value in the treatment of diabetes mellitus.", "contents": "Effect of somatostatin on blood sugar, plasma growth hormone, and glucagon levels in diabetic children. In nine children with clinically overt insulin-dependent diabetes mellitus the authors injected cyclic somatostatin (3 mug./kg. bolus, followed by infusion of 13 mug./kg. in 60 minutes) and measured blood glucose, plasma growth hormone, and glucagon concentrations throughout the infusion. The rapid administration produced no significant changes of these parameters. With the prolonged infusion there was a significant reduction of blood glucose from a mean of 148 +/- 19.7 to a mean of 88.5 +/- 18.1 mg./100 ml. (P less than 0.005) and of plasma glucagon from a basal mean of 33.3 +/- 2.4 to a minimum mean of 22.1 +/- 1.7 pg./ml. (P less than 0.01). There was a statistically significant correlation between the two parameters (0.01 less than P less than 0.05). Plasma GH values also diminished during the infusion, but the reduction was not statistically significant. These results show that somatostatin lowers blood glucose concentrations as a secondary effect of inhibition of glucagon secretion. Somatostatin is not suitable for therapy in diabetes. We speculate that a similar substance with a more prolonged and specific action on glucagon might prove of practical value in the treatment of diabetes mellitus."} {"id": "PMID:1278606", "title": "Evaluation of a 'true' fractional removal rate of glucose in man by bolus and simulated-ramp increase of glucose.", "content": "An infusion method designed to produce a gradual ramplike rise in plasma glucose levels in man showed that the observed slope of the ramp was not significantly different from the calculated slope only when both of the following parameters were used: 1. When the glucose disappearance rate coefficient (k) was calculated by an incremental method in which the fasting plasma glucose level was subtracted from each plasma glucose value obtained during a standard rapid intravenous glucose tolerance test. This proved to be superior to a contrasting method in which absolute glucose values are used for the semilogarithmic plot of glucose concentration versus time. 2. When the dilution technic was used to estimate directly the volume distribution of glucose rather than relying on standard reference tables that predict glucose distribution space in man. By using these two parameters obtained during standard intravenous glucose tolerance testing, we have shown that it is possible to calculate the rate of glucose infusion required to achieve successfully in man a ramp of plasma glucose of any desired steepness and to characterize the consequent insulin secretion. This simulated ramp increase of glucose provides a potentially useful tool for investigation of the dynamics of islet-cell function in man.", "contents": "Evaluation of a 'true' fractional removal rate of glucose in man by bolus and simulated-ramp increase of glucose. An infusion method designed to produce a gradual ramplike rise in plasma glucose levels in man showed that the observed slope of the ramp was not significantly different from the calculated slope only when both of the following parameters were used: 1. When the glucose disappearance rate coefficient (k) was calculated by an incremental method in which the fasting plasma glucose level was subtracted from each plasma glucose value obtained during a standard rapid intravenous glucose tolerance test. This proved to be superior to a contrasting method in which absolute glucose values are used for the semilogarithmic plot of glucose concentration versus time. 2. When the dilution technic was used to estimate directly the volume distribution of glucose rather than relying on standard reference tables that predict glucose distribution space in man. By using these two parameters obtained during standard intravenous glucose tolerance testing, we have shown that it is possible to calculate the rate of glucose infusion required to achieve successfully in man a ramp of plasma glucose of any desired steepness and to characterize the consequent insulin secretion. This simulated ramp increase of glucose provides a potentially useful tool for investigation of the dynamics of islet-cell function in man."} {"id": "PMID:1278607", "title": "Insulin response to oral glucose in patients with a previous myocardial infarction and in patients with peripheral vascular disease. Hyperinsulinism and its relationships to hypertriglyceridemia and overweight.", "content": "The insulin response to an oral glucose load (100 gm.) in 127 patients with a previous myocardial infarction (MI) (six months to one year) and in 65 patients with surgically treated or arteriographically identified peripheral vascular disease (PVD) was compared with that of 89 controls after matching the three collectives for age, glucose tolerance, and per cent ideal body weight (% IBW). The insulin response was of greater magnitude in MI and PVD groups than in respective control groups also in the absence of hyperglycemia, hypertriglyceridemia, and obesity. This finding suggests that hyperinsulinism may represent an early metabolic alteration associated with the development of MI and PVD. The insulin secretion pattern was prevalently of the delayed type in association with impaired glucose tolerance and with hypertriglyceridemia but not with overweight. Correlations between serum insulin, triglyceride (TG) levels, and % IBW were also investigated. We found a strong correlation (p less than 0.001) between stimulated insulin levels and % IBW in MI patients and none in PVD patients; conversely, the correlation between serum insulin and TG levels was very high (p less than 0.001) in PVD patients and only weak (p less than 0.05) in MI patients. No correlation was found between cholesterol (CH) levels and any of the other parameters studied. According to these results, it seems likely that hyperinsulinism plays a major role as a closely associated factor to obesity in those subjects who develop an MI, whereas in PVD patients the raised insulin levels may favor lipid accumulation in the arterial intima and accelerate the progress of atherosclerosis.", "contents": "Insulin response to oral glucose in patients with a previous myocardial infarction and in patients with peripheral vascular disease. Hyperinsulinism and its relationships to hypertriglyceridemia and overweight. The insulin response to an oral glucose load (100 gm.) in 127 patients with a previous myocardial infarction (MI) (six months to one year) and in 65 patients with surgically treated or arteriographically identified peripheral vascular disease (PVD) was compared with that of 89 controls after matching the three collectives for age, glucose tolerance, and per cent ideal body weight (% IBW). The insulin response was of greater magnitude in MI and PVD groups than in respective control groups also in the absence of hyperglycemia, hypertriglyceridemia, and obesity. This finding suggests that hyperinsulinism may represent an early metabolic alteration associated with the development of MI and PVD. The insulin secretion pattern was prevalently of the delayed type in association with impaired glucose tolerance and with hypertriglyceridemia but not with overweight. Correlations between serum insulin, triglyceride (TG) levels, and % IBW were also investigated. We found a strong correlation (p less than 0.001) between stimulated insulin levels and % IBW in MI patients and none in PVD patients; conversely, the correlation between serum insulin and TG levels was very high (p less than 0.001) in PVD patients and only weak (p less than 0.05) in MI patients. No correlation was found between cholesterol (CH) levels and any of the other parameters studied. According to these results, it seems likely that hyperinsulinism plays a major role as a closely associated factor to obesity in those subjects who develop an MI, whereas in PVD patients the raised insulin levels may favor lipid accumulation in the arterial intima and accelerate the progress of atherosclerosis."} {"id": "PMID:1278609", "title": "Somatosensory evoked cortical responses: detection in normal infants.", "content": "The detection of evoked cortical potentials to a peripheral stimulus is a possible method of studying sensory innervation in children. The purpose of the present study was to determine the consistency with which evoked responses to the electrical stimulation of nerve trunks can be recorded, and to assess the validity of computer analysis of the records. Automated analysis was felt to be desirable because the identification of evoked potentials is usually subjective. Recording sessions were carried out on 37 normal children between the ages of one and six months, and where possible were repeated on three occasions at intervals of at least one month. Using a rigid recording regime, evoked responses could be obtained in 90 to 95 per cent of sessions, the success rate varying with the site of stimulation. An objective computer analysis of records has been developed which is able to recognise evoked potentials as successfully as an experienced human observer.", "contents": "Somatosensory evoked cortical responses: detection in normal infants. The detection of evoked cortical potentials to a peripheral stimulus is a possible method of studying sensory innervation in children. The purpose of the present study was to determine the consistency with which evoked responses to the electrical stimulation of nerve trunks can be recorded, and to assess the validity of computer analysis of the records. Automated analysis was felt to be desirable because the identification of evoked potentials is usually subjective. Recording sessions were carried out on 37 normal children between the ages of one and six months, and where possible were repeated on three occasions at intervals of at least one month. Using a rigid recording regime, evoked responses could be obtained in 90 to 95 per cent of sessions, the success rate varying with the site of stimulation. An objective computer analysis of records has been developed which is able to recognise evoked potentials as successfully as an experienced human observer."} {"id": "PMID:1278610", "title": "The perception of passive joint-movements by cerebral-palsied children.", "content": "Luce's choice theory provided the psychophysical basis for investigating the ability of cerebral-palsied children to detect passive movement of the elbow joint. The method included testing \"yes\" responses when the forearm was moved, and \"false-alarm\" responses of \"yes\" when no arm movement had occurred. The children were tested with their eyes closed. The results showed that, in general, the children with spastic cerebral palsy had no deficits, or only very minor ones, in passive movement sensation. In contrast, the athetoid children had considerable deficits. It is suggested that the athetoid child is affected by a continuous barrage of irrelevant proprioceptive information and so finds difficulty in discriminating any particular proprioceptive cue.", "contents": "The perception of passive joint-movements by cerebral-palsied children. Luce's choice theory provided the psychophysical basis for investigating the ability of cerebral-palsied children to detect passive movement of the elbow joint. The method included testing \"yes\" responses when the forearm was moved, and \"false-alarm\" responses of \"yes\" when no arm movement had occurred. The children were tested with their eyes closed. The results showed that, in general, the children with spastic cerebral palsy had no deficits, or only very minor ones, in passive movement sensation. In contrast, the athetoid children had considerable deficits. It is suggested that the athetoid child is affected by a continuous barrage of irrelevant proprioceptive information and so finds difficulty in discriminating any particular proprioceptive cue."} {"id": "PMID:1278612", "title": "Light patterns as a means of assessing and recording gait. I: methods and results in normal children.", "content": "A method of analyzing and documenting gait in normal children is described. Patterns produced during walking, by means of lights situated at seven sites on the head, trunk and extremities, were recorded on color transparency film. With this technique, features of both normal and pathological gait are identifiable. The wide applicability of this method, its satisfactory reproducibility and uncomplicated design are emphasised.", "contents": "Light patterns as a means of assessing and recording gait. I: methods and results in normal children. A method of analyzing and documenting gait in normal children is described. Patterns produced during walking, by means of lights situated at seven sites on the head, trunk and extremities, were recorded on color transparency film. With this technique, features of both normal and pathological gait are identifiable. The wide applicability of this method, its satisfactory reproducibility and uncomplicated design are emphasised."} {"id": "PMID:1278614", "title": "The Landau reaction: a clinical and electromyographic analysis.", "content": "Thirty normal infants aged two months (N=10), five months (N=11) and eight months (N=9) participated in a three-month longitudinal study of the Landau reaction. Each infant's response to horizontal suspension was filmed and electromyographically recorded. Thoraco-lumbar extension and head elevation 90 degrees above the horizontal (face vertical to the horizontal) were present in 45 per cent of infants at four months and in 90 per cent of infants between five and 10 months. The postural response changed little between five and ten months of age. Less than 10 per cent of the infants regressed in postural response between monthly examinations. No infant hung limply over the examiner's hand, and electromyographic activity of the neck extensors never decreased to zero. All infants were able to reassume neck and spinal extension following active and passive flexion of the neck. Kicking activity was observed in 80 per cent of infants over four months of age. A pattern of motor responses for the normal infant was noted and variations from this pattern which have been observed in infants with motor dysfunction are discussed. The EMG recordings correlated well with the visual observations and provided an accurate written record of the responses. They proved to be a reliable research tool in the study of infants' gross motor responses.", "contents": "The Landau reaction: a clinical and electromyographic analysis. Thirty normal infants aged two months (N=10), five months (N=11) and eight months (N=9) participated in a three-month longitudinal study of the Landau reaction. Each infant's response to horizontal suspension was filmed and electromyographically recorded. Thoraco-lumbar extension and head elevation 90 degrees above the horizontal (face vertical to the horizontal) were present in 45 per cent of infants at four months and in 90 per cent of infants between five and 10 months. The postural response changed little between five and ten months of age. Less than 10 per cent of the infants regressed in postural response between monthly examinations. No infant hung limply over the examiner's hand, and electromyographic activity of the neck extensors never decreased to zero. All infants were able to reassume neck and spinal extension following active and passive flexion of the neck. Kicking activity was observed in 80 per cent of infants over four months of age. A pattern of motor responses for the normal infant was noted and variations from this pattern which have been observed in infants with motor dysfunction are discussed. The EMG recordings correlated well with the visual observations and provided an accurate written record of the responses. They proved to be a reliable research tool in the study of infants' gross motor responses."} {"id": "PMID:1278615", "title": "Cross-sectional study of developmental test items in children aged 94 to 97 weeks: report of the British Births Child Study.", "content": "A 10 percent random sample of legitimate children drawn from a national cohort of 16,955 live births were examined between 94 and 97 weeks of age by clinical medical officers, using a screening examination designed to detect children requiring further investigation for developmental delay. Girls were more advanced than boys, particularly at verbal and personal-social items, but care is needed in interpreting the significance of differences found in a single cross-sectional examination when the child is around the mean age for acquiring a particular skill. For many questions mothers also recorded their estimations of their children's abilities; these were appreciably greater than those of the examiner, the difference varying according to the difficulty of the task and whether they were questioned before or after the examiner had carried out the test. It is suggested that the results of a single screening examination at two years will depend upon the skill of the examiner (a) to persuade a child to co-operate or to be able to assess his ability, (b) to interpret the mother's estimation of her child's skill, and (c) to distinguish between late development and delay due to a handicapping condition.", "contents": "Cross-sectional study of developmental test items in children aged 94 to 97 weeks: report of the British Births Child Study. A 10 percent random sample of legitimate children drawn from a national cohort of 16,955 live births were examined between 94 and 97 weeks of age by clinical medical officers, using a screening examination designed to detect children requiring further investigation for developmental delay. Girls were more advanced than boys, particularly at verbal and personal-social items, but care is needed in interpreting the significance of differences found in a single cross-sectional examination when the child is around the mean age for acquiring a particular skill. For many questions mothers also recorded their estimations of their children's abilities; these were appreciably greater than those of the examiner, the difference varying according to the difficulty of the task and whether they were questioned before or after the examiner had carried out the test. It is suggested that the results of a single screening examination at two years will depend upon the skill of the examiner (a) to persuade a child to co-operate or to be able to assess his ability, (b) to interpret the mother's estimation of her child's skill, and (c) to distinguish between late development and delay due to a handicapping condition."} {"id": "PMID:1278616", "title": "Early identification of children likely to have specific learning difficulties: report of a follow-up.", "content": "In an earlier study, a group of pre-school children noted to have neurological dysfunction in the newborn period were given psychological tests and the results were compared with those from a control group of children with normal birth histories. The index children scored significantly more poorly on a number of items likely to lead to later learning difficulties at school(Frances Williams 1974). In the follow-up study, groups of the same index and control children were tested again between 8 and 9 1/2 of age. 11 of the 42 index children were unable to read, whereas there were no non-readers in the control group. A further 13 index children were backward by 12 months or more in reading accuracy, compared with five of the 43 control children. Only nine of the index children were reading at or above their appropriate age-level, compared with 22 of the controls. On a test for computational skill, many of the index children also scored much below the level expected for chronological age. These findings are discussed in relation to the possible identification of later learning difficulties from the results of pre-school examinations.", "contents": "Early identification of children likely to have specific learning difficulties: report of a follow-up. In an earlier study, a group of pre-school children noted to have neurological dysfunction in the newborn period were given psychological tests and the results were compared with those from a control group of children with normal birth histories. The index children scored significantly more poorly on a number of items likely to lead to later learning difficulties at school(Frances Williams 1974). In the follow-up study, groups of the same index and control children were tested again between 8 and 9 1/2 of age. 11 of the 42 index children were unable to read, whereas there were no non-readers in the control group. A further 13 index children were backward by 12 months or more in reading accuracy, compared with five of the 43 control children. Only nine of the index children were reading at or above their appropriate age-level, compared with 22 of the controls. On a test for computational skill, many of the index children also scored much below the level expected for chronological age. These findings are discussed in relation to the possible identification of later learning difficulties from the results of pre-school examinations."} {"id": "PMID:1278618", "title": "Unusual development of motor skills in a child with trisomy-18.", "content": "A child with trisomy-18 is reported who had by the age of four years developed motor skills considerably more advanced than any abilities previously noted in other children with this disorder. It is not possible to demonstrate how far this improvement was due to natural development, to physiotherapy, to the parent's handling or to other causes. However, if the degree of parental understanding, stimulation and participation in treatment has a significant effect on a child's progress, then further attempts to assess the value of physiotherapy for children should take this factor into consideration.", "contents": "Unusual development of motor skills in a child with trisomy-18. A child with trisomy-18 is reported who had by the age of four years developed motor skills considerably more advanced than any abilities previously noted in other children with this disorder. It is not possible to demonstrate how far this improvement was due to natural development, to physiotherapy, to the parent's handling or to other causes. However, if the degree of parental understanding, stimulation and participation in treatment has a significant effect on a child's progress, then further attempts to assess the value of physiotherapy for children should take this factor into consideration."} {"id": "PMID:1278622", "title": "Clinical aspects and long-term prognosis of intracranial tumours in infancy and childhood.", "content": "The long-term prognosis in 316 children (aged 0-14 years), in whom intracranial tumour was diagnosed during the years 1935 to 1959, has been evaluated. 196 patients survived for longer than four weeks after diagnosis or operation, and a total of 74 patients survived to follow-up after an observation period of 15 to 40 years. The prognosis for children with intracranial tumour is dependent on the age at which the diagnosis is made--the older the child the greater his chance of survival. However, in this study, the older-age group (10 to 14 years) also had the greatest number of recurrences after more than 10 years. A clinical history of more than six months is associated with a better prognosis. Long-term survival was independent of whether the tumour was supratentorial or infratentorial, but all patients with deep cerebral tumours and brain-stem tumours died within the observation period. Patients with intrapontine tumours had a very poor quality of life up to the time of death, whereas the majority of patients who survived for more than one year before recurrence were almost free from symptoms during the interval.", "contents": "Clinical aspects and long-term prognosis of intracranial tumours in infancy and childhood. The long-term prognosis in 316 children (aged 0-14 years), in whom intracranial tumour was diagnosed during the years 1935 to 1959, has been evaluated. 196 patients survived for longer than four weeks after diagnosis or operation, and a total of 74 patients survived to follow-up after an observation period of 15 to 40 years. The prognosis for children with intracranial tumour is dependent on the age at which the diagnosis is made--the older the child the greater his chance of survival. However, in this study, the older-age group (10 to 14 years) also had the greatest number of recurrences after more than 10 years. A clinical history of more than six months is associated with a better prognosis. Long-term survival was independent of whether the tumour was supratentorial or infratentorial, but all patients with deep cerebral tumours and brain-stem tumours died within the observation period. Patients with intrapontine tumours had a very poor quality of life up to the time of death, whereas the majority of patients who survived for more than one year before recurrence were almost free from symptoms during the interval."} {"id": "PMID:1278623", "title": "Agenesis of the corpus callosum revealed by computerized tomography.", "content": "Computerized tomography is a new, safe, non-invasive method of diagnosing intracranial disorders. It has been used in the detection of intracranial tumors, hydrocephalus, hemorrhages, atrophy, abscesses and subdural hematomata. Two cases of agenesis of the corpus callosum are presented, in which the diagnosis was made or confirmed by computerized tomography. The embryology, clinical course and radiological aspects of the disorder are reviewed.", "contents": "Agenesis of the corpus callosum revealed by computerized tomography. Computerized tomography is a new, safe, non-invasive method of diagnosing intracranial disorders. It has been used in the detection of intracranial tumors, hydrocephalus, hemorrhages, atrophy, abscesses and subdural hematomata. Two cases of agenesis of the corpus callosum are presented, in which the diagnosis was made or confirmed by computerized tomography. The embryology, clinical course and radiological aspects of the disorder are reviewed."} {"id": "PMID:1278624", "title": "The functions and the training of a paediatric neurologist.", "content": "A total of 2018 office referrals of children with neurological problems is compared with 635 adult neurological referrals in the same Canadian city. Data of children and adults admitted to hospital with neurological problems are also compared. It is suggested that the different types of caseload encountered justify changes in the training programs for paediatric neurologists.", "contents": "The functions and the training of a paediatric neurologist. A total of 2018 office referrals of children with neurological problems is compared with 635 adult neurological referrals in the same Canadian city. Data of children and adults admitted to hospital with neurological problems are also compared. It is suggested that the different types of caseload encountered justify changes in the training programs for paediatric neurologists."} {"id": "PMID:1278625", "title": "Opening windows into a child's mind.", "content": "Children may not know, or cannot tell, what is causing their psychosomatic symptoms. Methods are outlined which may help paediatricians to see what goes on in children's minds and also help children to express it. For some children, such expression may itself be healing: for others, further help will be needed. Interested paediatricians will learn to distinguish between these groups.", "contents": "Opening windows into a child's mind. Children may not know, or cannot tell, what is causing their psychosomatic symptoms. Methods are outlined which may help paediatricians to see what goes on in children's minds and also help children to express it. For some children, such expression may itself be healing: for others, further help will be needed. Interested paediatricians will learn to distinguish between these groups."} {"id": "PMID:1278626", "title": "Epilepsy: a neurological complication of thalidomide embryopathy.", "content": "The possibility of epilepsy resulting from maternal thalidomide ingestion was investigated by obtaining a telephoned neurological history from all suspect families in the United Kingdom in which the specific diagnosis was uncertain. The annual incidence in the first seven years of life was found to be five times the figure for the general population, and the prevalence of active epilepsy is significantly increased in the teenage thalidomide population. That this increased incidence and prevalence of epilepsy is not a chance observation is supported by published clinical and experimental evidence of central nervous system abnormalities in thalidomide embryopathy, in addition to the known neurological effects of the drug in the adult.", "contents": "Epilepsy: a neurological complication of thalidomide embryopathy. The possibility of epilepsy resulting from maternal thalidomide ingestion was investigated by obtaining a telephoned neurological history from all suspect families in the United Kingdom in which the specific diagnosis was uncertain. The annual incidence in the first seven years of life was found to be five times the figure for the general population, and the prevalence of active epilepsy is significantly increased in the teenage thalidomide population. That this increased incidence and prevalence of epilepsy is not a chance observation is supported by published clinical and experimental evidence of central nervous system abnormalities in thalidomide embryopathy, in addition to the known neurological effects of the drug in the adult."} {"id": "PMID:1278627", "title": "An approach to head, neck and trunk stabilization and control in cerebral palsy by use of the Milwaukee brace.", "content": "This paper reports the successful use of the Milwaukee brace in nine children with cerebral palsy and lack of head, neck and body control. After an initial period of apprehension, the brace has been approved by the patients themselves, their families, teachers and therapists and has added greatly to the quality of life within the limits of the patients' abilities. Follow-up has ranged from three months to five years (mean 3 1/2 years) and no deleterious effects have been noted.", "contents": "An approach to head, neck and trunk stabilization and control in cerebral palsy by use of the Milwaukee brace. This paper reports the successful use of the Milwaukee brace in nine children with cerebral palsy and lack of head, neck and body control. After an initial period of apprehension, the brace has been approved by the patients themselves, their families, teachers and therapists and has added greatly to the quality of life within the limits of the patients' abilities. Follow-up has ranged from three months to five years (mean 3 1/2 years) and no deleterious effects have been noted."} {"id": "PMID:1278628", "title": "Quantitative assessment of oral tactile sensitivity in pre-term and term neonates, and comparison with adults.", "content": "The tongues of 34 infants between 31 and 40 weeks estimated gestational age were stimulated with filament esthesiometers. Stereotyped ipsilateral movements of the tongue were elicited in all infants. An assessment of tactile sensitivity based on this reflex is minimally affected by infant activity state and habituation to repeated stimulation. Small pre-term infants (31 to 35 weeks gestation) and infants born near term (37 to 40 weeks gestation) were more sensitive to tactile stimulation than an intermediate group (35 to 37 weeks gestation). In infants followed longitudinally, a transient decrement in sensitivity occurred at two weeks postnatal age. The tactile sensitivity in 12 adults (as measured by their correct reports of stimulus location) was far greater than the sensitivity of the infants.", "contents": "Quantitative assessment of oral tactile sensitivity in pre-term and term neonates, and comparison with adults. The tongues of 34 infants between 31 and 40 weeks estimated gestational age were stimulated with filament esthesiometers. Stereotyped ipsilateral movements of the tongue were elicited in all infants. An assessment of tactile sensitivity based on this reflex is minimally affected by infant activity state and habituation to repeated stimulation. Small pre-term infants (31 to 35 weeks gestation) and infants born near term (37 to 40 weeks gestation) were more sensitive to tactile stimulation than an intermediate group (35 to 37 weeks gestation). In infants followed longitudinally, a transient decrement in sensitivity occurred at two weeks postnatal age. The tactile sensitivity in 12 adults (as measured by their correct reports of stimulus location) was far greater than the sensitivity of the infants."} {"id": "PMID:1278629", "title": "Fetal spinal-cord injury secondary to hyperextension of the neck: no effect of caesarean section.", "content": "A 24-month-old Japanese girl is reported who had upper spinal-cord injury secondary to fetal hyperextension of the neck in breech presentation. She was first noted to be in this position 10 days before the expected date of birth and was delivered by caesarean section.", "contents": "Fetal spinal-cord injury secondary to hyperextension of the neck: no effect of caesarean section. A 24-month-old Japanese girl is reported who had upper spinal-cord injury secondary to fetal hyperextension of the neck in breech presentation. She was first noted to be in this position 10 days before the expected date of birth and was delivered by caesarean section."} {"id": "PMID:1278630", "title": "Lactic acidaemia due to hyperventilation in a child with severe mental retardation.", "content": "A 16-year-old girl with severe mental retardation of unknown aetiology presented with increased blood content of lactate and pyruvate. It was demonstrated that the biochemical abnormalities were due to hyperventilation.", "contents": "Lactic acidaemia due to hyperventilation in a child with severe mental retardation. A 16-year-old girl with severe mental retardation of unknown aetiology presented with increased blood content of lactate and pyruvate. It was demonstrated that the biochemical abnormalities were due to hyperventilation."} {"id": "PMID:1278635", "title": "An animal model of fulminant hepatic failure: a feasibility study.", "content": "An attempt was made to produce animal model of fulminant hepatic failure in the pig by intragastric administration of acetaminophen (N-acetyl-p-aminophenol). The effect of varying doses was observed in phenobarbital-pretreated and untreated animals. Assessment of optimal dose was made in terms of duration of survival and coma in animals exhibiting biochemical and histological evidence of liver necrosis. Significant liver necrosis was observed in enzyme-induced pigs only, whereas in the noninduced pigs respiratory arrest was considered a likely cause of death. Although liver necrosis occurred consistently at a dose of 0.5 to 1.1 g per kg of acetaminophen in phenobarbital-pretreated animals, survival time and coma duration were unpredictable. Only one-fifth of the total number of phenobarbital-pretreated pigs administered acetaminophen in this dose range fulfilled the prescribed criteria for a satisfactory model. There was a good correlation between survival time and duration of coma, although survival time did not correlate with acetaminophen dose, or with any of the following: peak plasma acetaminophen levels, thrombocytopenia, fall in hematocrit or fibrinogen, or alteration in other biochemical parameters. In addition to the unpredictable duration of survival and coma, the occurrence of acute anemia in 60% of the enzyme-induced animals was a major detraction from the possible usefulness of this model to evaluate various therapeutic regimes.", "contents": "An animal model of fulminant hepatic failure: a feasibility study. An attempt was made to produce animal model of fulminant hepatic failure in the pig by intragastric administration of acetaminophen (N-acetyl-p-aminophenol). The effect of varying doses was observed in phenobarbital-pretreated and untreated animals. Assessment of optimal dose was made in terms of duration of survival and coma in animals exhibiting biochemical and histological evidence of liver necrosis. Significant liver necrosis was observed in enzyme-induced pigs only, whereas in the noninduced pigs respiratory arrest was considered a likely cause of death. Although liver necrosis occurred consistently at a dose of 0.5 to 1.1 g per kg of acetaminophen in phenobarbital-pretreated animals, survival time and coma duration were unpredictable. Only one-fifth of the total number of phenobarbital-pretreated pigs administered acetaminophen in this dose range fulfilled the prescribed criteria for a satisfactory model. There was a good correlation between survival time and duration of coma, although survival time did not correlate with acetaminophen dose, or with any of the following: peak plasma acetaminophen levels, thrombocytopenia, fall in hematocrit or fibrinogen, or alteration in other biochemical parameters. In addition to the unpredictable duration of survival and coma, the occurrence of acute anemia in 60% of the enzyme-induced animals was a major detraction from the possible usefulness of this model to evaluate various therapeutic regimes."} {"id": "PMID:1278636", "title": "Alcohol, amino acids, and albumin synthesis. II. Alcohol inhibition of albumin synthesis reversed by arginine and spermine.", "content": "The effects of alcohol and spermine on albumin synthesis and polysome aggregation were studied in the isolated perfused rabbit liver system. Fed or fasted males served as donors and the perfusate contained, singly or in combination, alcohol, 200 mg per 100 ml, spermine, 1 mM, and arginine, 10 mM. The results indicate that in the presence of alcohol, using a liver from a fed donor, albumin synthesis is depressed from 16 to 6 mg per 100 g of wet liver weight per hr and the bound polysome is disaggregated. Spermine partially reaggregates the bound polysome and a combination of spermine and arginine augments albumin synthesis to the control rate. When the donor is fasted, and alcohol is present in the perfusate, the addition of spermine results in aggregated bound and free polysome patterns, whereas the combination of arginine and spermine is necessary to restimulate albumin synthesis. The results indicate that spermine plays an important role in the integrity of the polysome system and that arginine and spermine appears synergistic in maintaining albumin synthesis.", "contents": "Alcohol, amino acids, and albumin synthesis. II. Alcohol inhibition of albumin synthesis reversed by arginine and spermine. The effects of alcohol and spermine on albumin synthesis and polysome aggregation were studied in the isolated perfused rabbit liver system. Fed or fasted males served as donors and the perfusate contained, singly or in combination, alcohol, 200 mg per 100 ml, spermine, 1 mM, and arginine, 10 mM. The results indicate that in the presence of alcohol, using a liver from a fed donor, albumin synthesis is depressed from 16 to 6 mg per 100 g of wet liver weight per hr and the bound polysome is disaggregated. Spermine partially reaggregates the bound polysome and a combination of spermine and arginine augments albumin synthesis to the control rate. When the donor is fasted, and alcohol is present in the perfusate, the addition of spermine results in aggregated bound and free polysome patterns, whereas the combination of arginine and spermine is necessary to restimulate albumin synthesis. The results indicate that spermine plays an important role in the integrity of the polysome system and that arginine and spermine appears synergistic in maintaining albumin synthesis."} {"id": "PMID:1278637", "title": "Double lumen esophagus due to reflux esophagitis with fibrous septom formation.", "content": "The unique endoscopic finding of a double lumen esophagus due to the development of a fibrous septum within an area of peptic reflux esophagitis is presented. The pathogenesis of this septum was felt to represent adherence to granulation tissue from opposing esophageal walls. This abnormality was easily managed by esophageal bouginage.", "contents": "Double lumen esophagus due to reflux esophagitis with fibrous septom formation. The unique endoscopic finding of a double lumen esophagus due to the development of a fibrous septum within an area of peptic reflux esophagitis is presented. The pathogenesis of this septum was felt to represent adherence to granulation tissue from opposing esophageal walls. This abnormality was easily managed by esophageal bouginage."} {"id": "PMID:1278638", "title": "Endoscopic retrograde cholangiopancreatography in familial pancreatitis.", "content": "A young man and his father, both with pancreatitis, were recently seen at the Mayo Clinic. The histories, physical findings, and laboratory values were those of chronic pancreatitis. Endoscopic retrograde cholangiopancreatography was valuable in confirming the gross pathological changes and in orienting the surgeon preoperatively.", "contents": "Endoscopic retrograde cholangiopancreatography in familial pancreatitis. A young man and his father, both with pancreatitis, were recently seen at the Mayo Clinic. The histories, physical findings, and laboratory values were those of chronic pancreatitis. Endoscopic retrograde cholangiopancreatography was valuable in confirming the gross pathological changes and in orienting the surgeon preoperatively."} {"id": "PMID:1278639", "title": "Tumor-induced acute pancreatitis.", "content": "Primary neoplasms of the pancreas and tumors metastatic to the pancreas are capable of initiating an epidode of acute pancreatitis severe enough to cause the development of a pancreatic pseudocyst and ascites. There are now three case reports of bronchogenic carcinoma metastatic to the pancreas causing acute pancreatitis. In the present case, there was histological evidence of rupture of pancreatic ducts by tumor and obstruction of ducts by nests of tumor cells.", "contents": "Tumor-induced acute pancreatitis. Primary neoplasms of the pancreas and tumors metastatic to the pancreas are capable of initiating an epidode of acute pancreatitis severe enough to cause the development of a pancreatic pseudocyst and ascites. There are now three case reports of bronchogenic carcinoma metastatic to the pancreas causing acute pancreatitis. In the present case, there was histological evidence of rupture of pancreatic ducts by tumor and obstruction of ducts by nests of tumor cells."} {"id": "PMID:1278640", "title": "Gastric ulcers in the fundic gland area.", "content": "Gastric ulcers have been thought to occur only in the pyloric gland area. However, endoscopic examinations using the Congo red test showed that 18 of the ulcers examined (7.8%) were surrounded by an acid-secreting area, and so were in the fundic gland area. Histological examination of specimens obtained by gastrectomy also showed that five of the lesions examined (4.5%) were located in the fundic gland area. Ulcers in the fundic gland area were found most frequently in the angle and lower gastric body, adjacent to acid-secreting boundary. These ulcers were associated with little or no fundal gastritis, whereas ulcers in the pyloric gland area were usually associated with moderate or severe fundal gastritis. Unlike ulcers of similar depth in the pyloric gland area, ulcers surrounded by normal fundic mucosa healed rapidly and completely. No recurrence of these ulcers was seen in a 1-year endoscopic follow-up period.", "contents": "Gastric ulcers in the fundic gland area. Gastric ulcers have been thought to occur only in the pyloric gland area. However, endoscopic examinations using the Congo red test showed that 18 of the ulcers examined (7.8%) were surrounded by an acid-secreting area, and so were in the fundic gland area. Histological examination of specimens obtained by gastrectomy also showed that five of the lesions examined (4.5%) were located in the fundic gland area. Ulcers in the fundic gland area were found most frequently in the angle and lower gastric body, adjacent to acid-secreting boundary. These ulcers were associated with little or no fundal gastritis, whereas ulcers in the pyloric gland area were usually associated with moderate or severe fundal gastritis. Unlike ulcers of similar depth in the pyloric gland area, ulcers surrounded by normal fundic mucosa healed rapidly and completely. No recurrence of these ulcers was seen in a 1-year endoscopic follow-up period."} {"id": "PMID:1278646", "title": "Effect of secretin on gastric function in normal subjects and in patients with duodenal ulcer.", "content": "The effect of constant intravenous infusion of secretin in doses of 0.25, 0.50, 1.50, and 3.0 mug per kg per hr on meal-stimulated acid secretion was measured in vitro titration to pH 5.0. The pattern and degree of secretin inhibition of food-stimulated acid secretion depended on when the secretin infusion was begun, the effect being more pronounced when the secretin was begun 1 hr before the test meal than when the meal and secretin infusions were begun simultaneously. Inhibition of acid secretion in normals was approximately the same as in 2 patients with pancreatic exocrine insufficiency who could secrete only small amounts of pancreatic bicarbonate in response to secretin. Secretin in dose of 0.25 and 0.5 mug per kg per hr inhibited acid secretion only slightly, whereas 3.0 mug per kg per hr completely stopped acid secretion. Inhibition of acid secretion by secretin was similar in controls and in patients with duodenal ulcer. Secretin also reduced the rise in serum gastrin concentration after the meal, and delayed gastric emptying; both responses were approximately the same in normals and in duodenal ulcer patients. Secretin inhibited basal gastric acid secretion but had no consistent effect on basal serum gastrin concentration.", "contents": "Effect of secretin on gastric function in normal subjects and in patients with duodenal ulcer. The effect of constant intravenous infusion of secretin in doses of 0.25, 0.50, 1.50, and 3.0 mug per kg per hr on meal-stimulated acid secretion was measured in vitro titration to pH 5.0. The pattern and degree of secretin inhibition of food-stimulated acid secretion depended on when the secretin infusion was begun, the effect being more pronounced when the secretin was begun 1 hr before the test meal than when the meal and secretin infusions were begun simultaneously. Inhibition of acid secretion in normals was approximately the same as in 2 patients with pancreatic exocrine insufficiency who could secrete only small amounts of pancreatic bicarbonate in response to secretin. Secretin in dose of 0.25 and 0.5 mug per kg per hr inhibited acid secretion only slightly, whereas 3.0 mug per kg per hr completely stopped acid secretion. Inhibition of acid secretion by secretin was similar in controls and in patients with duodenal ulcer. Secretin also reduced the rise in serum gastrin concentration after the meal, and delayed gastric emptying; both responses were approximately the same in normals and in duodenal ulcer patients. Secretin inhibited basal gastric acid secretion but had no consistent effect on basal serum gastrin concentration."} {"id": "PMID:1278647", "title": "Effect of metoclopramide in chronic gastric retention after gastric surgery.", "content": "The effect of metoclopramide, a stimulant of gastric motility, on gastric emptying was tested in 6 patients with chronic gastric retention after vagotomy and gastric resection, unexplained by mechanical obstruction or stomal ulceration. Gastric emptying was measured using a gamma camera technique and a solid meal labeled with 99mtechnetium-labeled diethylenetriaminepentaacetic acid. Metoclopramide produced a 2.6-fold increase in gastric emptying in the first 90 min after eating the meal, compared to placebo (P less than 0.01). Metoclopramide did not alter gastric emptying in 8 normal volunteers. These data indicate that metoclopramide may be useful in treatment of patients with chronically impaired gastric emptying after gastric surgery.", "contents": "Effect of metoclopramide in chronic gastric retention after gastric surgery. The effect of metoclopramide, a stimulant of gastric motility, on gastric emptying was tested in 6 patients with chronic gastric retention after vagotomy and gastric resection, unexplained by mechanical obstruction or stomal ulceration. Gastric emptying was measured using a gamma camera technique and a solid meal labeled with 99mtechnetium-labeled diethylenetriaminepentaacetic acid. Metoclopramide produced a 2.6-fold increase in gastric emptying in the first 90 min after eating the meal, compared to placebo (P less than 0.01). Metoclopramide did not alter gastric emptying in 8 normal volunteers. These data indicate that metoclopramide may be useful in treatment of patients with chronically impaired gastric emptying after gastric surgery."} {"id": "PMID:1278648", "title": "The mechanism of hypergastrinemia in achlorhydria. Effect of food, acid, and calcitonin on serum gastrin concentrations and component pattern in pernicious anemia, with correlation to endogenous secretin concentrations in plasma.", "content": "The effect of protein-rich food, intravenous calcitonin injections, and intragastric instillation of hydrochloric acid on serum gastrin concentrations and gastrin component pattern was studied in hypergastrinemic patients (pernicious anemia) and matched control subjects. Moreover, plasma secretin concentrations were measured during intragastric acidification. The intragastric acidification resulted in rapid fall in serum gastrin concentrations, although not below the upper limit of normal range. The small components, III (gastrin-17-like) and IV (gastrin-13-like), almost disappeared, whereas the concentrations of component I and component II (gastrin-34-like) were less affected. The increase in secretin concentrations after intragastric acidification was smaller in patients with pernicious anemia than in normal subjects, although the difference was not significant. In contrast to the results in normal control subjects, neither food nor calcitonin produced significant variations in serum gastrin concentrations and gastrin component pattern of pernicious anemia patients. The failure of food to stimulate and of calcitonin to inhibit release of gastrin in the majority of pernicious anemia patients might suggest that gastrin secretion in these patients is autonomous. However, considering the recently recognized slow metabolic clearance rate of big gastrins, the effect of intragastric acidification suggests that the mechanism for acid inhibition of the antral gastrin secretion is intact in patients with achlorhydria.", "contents": "The mechanism of hypergastrinemia in achlorhydria. Effect of food, acid, and calcitonin on serum gastrin concentrations and component pattern in pernicious anemia, with correlation to endogenous secretin concentrations in plasma. The effect of protein-rich food, intravenous calcitonin injections, and intragastric instillation of hydrochloric acid on serum gastrin concentrations and gastrin component pattern was studied in hypergastrinemic patients (pernicious anemia) and matched control subjects. Moreover, plasma secretin concentrations were measured during intragastric acidification. The intragastric acidification resulted in rapid fall in serum gastrin concentrations, although not below the upper limit of normal range. The small components, III (gastrin-17-like) and IV (gastrin-13-like), almost disappeared, whereas the concentrations of component I and component II (gastrin-34-like) were less affected. The increase in secretin concentrations after intragastric acidification was smaller in patients with pernicious anemia than in normal subjects, although the difference was not significant. In contrast to the results in normal control subjects, neither food nor calcitonin produced significant variations in serum gastrin concentrations and gastrin component pattern of pernicious anemia patients. The failure of food to stimulate and of calcitonin to inhibit release of gastrin in the majority of pernicious anemia patients might suggest that gastrin secretion in these patients is autonomous. However, considering the recently recognized slow metabolic clearance rate of big gastrins, the effect of intragastric acidification suggests that the mechanism for acid inhibition of the antral gastrin secretion is intact in patients with achlorhydria."} {"id": "PMID:1278649", "title": "Studies on the mechanism of esophagitis-induced lower esophageal sphincter hypotension in cats.", "content": "Perfusion of 0.1 n HC1 5 cm above the lower esophageal sphincter (LES) in cats for 30 min on 4 consecutive days produced biopsy-documented esophagitis and marked decreases in LES pressure. Using this model the effects of experimental esophagitis on the LES response to edrophonium, pentagastrin, and bethanechol were determined. The sphincter response to both edrophonium and pentagastrin after esophagitis was induced was significantly less than preperfusion responses. When the esophagitis had resolved, the pressure response to edrophonium and pentagastrin returned to preperfusion levels. In contrast, the sphincter response to bethanechol during esophagitis was not different from the preperfusion response and remained unchanged after resolution of the esophagitis. Lower esophageal smooth muscle taken from cats with active esophagitis appeared normal by both light and electron microscopy. These studies indicate that besides decreasing resting LES tone, esophageal inflammation causes functional impairment of a cholinergic mechanism regulating LES pressure. In contrast, the smooth muscle appears to be unaffected by inflammation despite the LES hypotension.", "contents": "Studies on the mechanism of esophagitis-induced lower esophageal sphincter hypotension in cats. Perfusion of 0.1 n HC1 5 cm above the lower esophageal sphincter (LES) in cats for 30 min on 4 consecutive days produced biopsy-documented esophagitis and marked decreases in LES pressure. Using this model the effects of experimental esophagitis on the LES response to edrophonium, pentagastrin, and bethanechol were determined. The sphincter response to both edrophonium and pentagastrin after esophagitis was induced was significantly less than preperfusion responses. When the esophagitis had resolved, the pressure response to edrophonium and pentagastrin returned to preperfusion levels. In contrast, the sphincter response to bethanechol during esophagitis was not different from the preperfusion response and remained unchanged after resolution of the esophagitis. Lower esophageal smooth muscle taken from cats with active esophagitis appeared normal by both light and electron microscopy. These studies indicate that besides decreasing resting LES tone, esophageal inflammation causes functional impairment of a cholinergic mechanism regulating LES pressure. In contrast, the smooth muscle appears to be unaffected by inflammation despite the LES hypotension."} {"id": "PMID:1278650", "title": "Giardiasis in the mouse: an animal model.", "content": "An animal model for giardiasis was developed using Giardia muris in Swiss albino mice. Intraesophageal inoculation of G. muris cysts caused a reproducible pattern of infection, with trophozoite and cyst counts reaching a maximum on days 5 to 14 after cyst inoculation and thereafter showing a progressive decline. Spontaneous resolution of infection occurred in most mice after 21 to 28 days. When compared to uninfected controls, Giardia-infected mice had significant impairment of weight gain and a significant reduction in the villus to crypt ratio of jejunal mucosa. Although maximal trophozoite and cyst counts were independent of the size of the cyst inoculum, those mice receiving inoculations of larger numbers of cysts showed earlier attainment of maximal counts, greater impariment of weight gain, and earlier and more severe small bowel changes than mice receiving inoculations of smaller numbers of cysts. This model offers unique opportunities for study of this poorly understood gastrointestinal parasite.", "contents": "Giardiasis in the mouse: an animal model. An animal model for giardiasis was developed using Giardia muris in Swiss albino mice. Intraesophageal inoculation of G. muris cysts caused a reproducible pattern of infection, with trophozoite and cyst counts reaching a maximum on days 5 to 14 after cyst inoculation and thereafter showing a progressive decline. Spontaneous resolution of infection occurred in most mice after 21 to 28 days. When compared to uninfected controls, Giardia-infected mice had significant impairment of weight gain and a significant reduction in the villus to crypt ratio of jejunal mucosa. Although maximal trophozoite and cyst counts were independent of the size of the cyst inoculum, those mice receiving inoculations of larger numbers of cysts showed earlier attainment of maximal counts, greater impariment of weight gain, and earlier and more severe small bowel changes than mice receiving inoculations of smaller numbers of cysts. This model offers unique opportunities for study of this poorly understood gastrointestinal parasite."} {"id": "PMID:1278651", "title": "Genesis of basal sphincter pressure: effect of tetrodotoxin on lower esophageal sphincter pressure in opossum in vivo.", "content": "Currently it is believed that lower esophageal sphincter closure is maintained by tonic neurohormonal activity. Studies were performed to evaluate the role of neural and myogenic activity in the genesis of resting sphincter pressure in the opossum. The neural activity in the sphincter was blocked by intravenous administration of the puffer fish poison, tetrodotoxin, in intact animals. The respiration in these animals was assisted with a respirator, their blood pressure was supported by intravenous administration of Ringer's solution, and their body temperature was maintained by heating lamp. The lower esophageal sphincter pressures were measured with water-filled and continuously perfused catheters which were anchored to the lower esophageal sphincter using a new technique. Tetrodotoxin blocked the sphincter response to neural stimulation with vagal stimulation, esophageal distention, and local electrical stimulation of the sphincter. The mean resting sphincter pressure before tetrodotoxin was 59.0 +/- 2.6 mm Hg, and it was 64.4 +/- 6.9 mm Hg after tetrodotoxin (P greater than 0.05). During neural block with tetrodotoxin, the sphincter response to administration of isoproterenol or bethanechol was similar to that during the control period (P greater than 0.05). These studies show that: (1) Tetrodotoxin can be administered in intact animals to achieve complete block of neural activity in the lower esophageal sphincter; (2) sphincter muscle is not adversely affected by tetrodotoxin; and (3) block of neural activity does not alter the resting lower esophageal sphincter pressure.", "contents": "Genesis of basal sphincter pressure: effect of tetrodotoxin on lower esophageal sphincter pressure in opossum in vivo. Currently it is believed that lower esophageal sphincter closure is maintained by tonic neurohormonal activity. Studies were performed to evaluate the role of neural and myogenic activity in the genesis of resting sphincter pressure in the opossum. The neural activity in the sphincter was blocked by intravenous administration of the puffer fish poison, tetrodotoxin, in intact animals. The respiration in these animals was assisted with a respirator, their blood pressure was supported by intravenous administration of Ringer's solution, and their body temperature was maintained by heating lamp. The lower esophageal sphincter pressures were measured with water-filled and continuously perfused catheters which were anchored to the lower esophageal sphincter using a new technique. Tetrodotoxin blocked the sphincter response to neural stimulation with vagal stimulation, esophageal distention, and local electrical stimulation of the sphincter. The mean resting sphincter pressure before tetrodotoxin was 59.0 +/- 2.6 mm Hg, and it was 64.4 +/- 6.9 mm Hg after tetrodotoxin (P greater than 0.05). During neural block with tetrodotoxin, the sphincter response to administration of isoproterenol or bethanechol was similar to that during the control period (P greater than 0.05). These studies show that: (1) Tetrodotoxin can be administered in intact animals to achieve complete block of neural activity in the lower esophageal sphincter; (2) sphincter muscle is not adversely affected by tetrodotoxin; and (3) block of neural activity does not alter the resting lower esophageal sphincter pressure."} {"id": "PMID:1278652", "title": "Evidence for a single common carrier for uptake of a dipeptide and a tripeptide by hamster jejunum in vitro.", "content": "This paper describes an investigation of whether a dipeptide and a tripeptide were taken up by hamster jejunum by the same transport system, or whether there was evidence of uptake by more than one transport system. The work was carried out with rings of everted hamster jejunum in vitro, under conditions of influx, using the \"model\" peptides glycylsarcosine, glycylsarcosylsarcosine, and glycylsarcosylsarcosylsarcosine. These peptides are all exceptionally resistant to hydrolysis, appearing intact in the rings, and the di- and tripeptide have previously been shown to be concentrated in the rings by active transport. The results showed that influx of glycylsarcosine was inhibited by glycylsarcosylsarcosine in a competitive way, and that each of the peptides was capable of causing virtually complete inhibition of influx of the other. Glycylsarcosylsarcosylsarcosine had no effect on influx of glycylsarcosine or of glycylsarcosylsarcosine. It was concluded that although the existence of multiple transport systems shared by both glycylsarcosine and glycylsarcosylsarcosine could not be ruled out, the simplest hypothesis was that both the dipeptide and the tripeptide shared a single common carrier for uptake. The tetrapeptide glycylsarcosylsarcosylsarcosine was apparently not transported by this carrier, in agreement with previous results. The possible effects of the \"unstirred layer\" were taken into account in considering the results and are discussed. They do not alter the conclusions reached.", "contents": "Evidence for a single common carrier for uptake of a dipeptide and a tripeptide by hamster jejunum in vitro. This paper describes an investigation of whether a dipeptide and a tripeptide were taken up by hamster jejunum by the same transport system, or whether there was evidence of uptake by more than one transport system. The work was carried out with rings of everted hamster jejunum in vitro, under conditions of influx, using the \"model\" peptides glycylsarcosine, glycylsarcosylsarcosine, and glycylsarcosylsarcosylsarcosine. These peptides are all exceptionally resistant to hydrolysis, appearing intact in the rings, and the di- and tripeptide have previously been shown to be concentrated in the rings by active transport. The results showed that influx of glycylsarcosine was inhibited by glycylsarcosylsarcosine in a competitive way, and that each of the peptides was capable of causing virtually complete inhibition of influx of the other. Glycylsarcosylsarcosylsarcosine had no effect on influx of glycylsarcosine or of glycylsarcosylsarcosine. It was concluded that although the existence of multiple transport systems shared by both glycylsarcosine and glycylsarcosylsarcosine could not be ruled out, the simplest hypothesis was that both the dipeptide and the tripeptide shared a single common carrier for uptake. The tetrapeptide glycylsarcosylsarcosylsarcosine was apparently not transported by this carrier, in agreement with previous results. The possible effects of the \"unstirred layer\" were taken into account in considering the results and are discussed. They do not alter the conclusions reached."} {"id": "PMID:1278653", "title": "Metabolism of chenodeoxycholate by intestinal mucosa.", "content": "The metabolism of 14C-labeled bile salts was studied in vitro during their absorption from infused segments of rat intestine. The transported bile salts were recovered in transudates which were collected from the serosal surface of infused segments. In the jejunum, 36% of transported [14C]deoxycholate and 48% of transported [14C]chenodeoxycholate were recovered as metabolites which migrated as a seemingly single polar compound on thin layer chromatography; 52 to 72% of these metabolites could be deconjugated by cholylglycine hydrolase to yield original [14C]deoxycholate or [14C]chenodeoxycholate, respectively. The jejunum metabolized 9 times more [14C]chenodeoxycholate than the ileum (38.1 nmoles per hr per g compared with 4.2 nmoles per hr per g), despite the fact that both segments transferred the same amount of radioactivity. In contrast, [14C]cholate, [14C]glycocholate, and [14C]glycodeoxycholate were transferred intact by the jejunum, ileum, and colon. Human jejunal and rectal mucosa were able to metabolize [14C]chenodeoxycholate to polar metabolites in vitro. Polar metabolites were also found in the portal plasma and jejunal wall 20 min after the feeding of [14C]chenodeoxycholate to bile fistula rats. It is suggested that these results complicate the interpretation of in vitro experiments on absorption of dihydroxy bile salts, and that they indicate that the human small intestine may be able to metabolize chenodeoxycholate.", "contents": "Metabolism of chenodeoxycholate by intestinal mucosa. The metabolism of 14C-labeled bile salts was studied in vitro during their absorption from infused segments of rat intestine. The transported bile salts were recovered in transudates which were collected from the serosal surface of infused segments. In the jejunum, 36% of transported [14C]deoxycholate and 48% of transported [14C]chenodeoxycholate were recovered as metabolites which migrated as a seemingly single polar compound on thin layer chromatography; 52 to 72% of these metabolites could be deconjugated by cholylglycine hydrolase to yield original [14C]deoxycholate or [14C]chenodeoxycholate, respectively. The jejunum metabolized 9 times more [14C]chenodeoxycholate than the ileum (38.1 nmoles per hr per g compared with 4.2 nmoles per hr per g), despite the fact that both segments transferred the same amount of radioactivity. In contrast, [14C]cholate, [14C]glycocholate, and [14C]glycodeoxycholate were transferred intact by the jejunum, ileum, and colon. Human jejunal and rectal mucosa were able to metabolize [14C]chenodeoxycholate to polar metabolites in vitro. Polar metabolites were also found in the portal plasma and jejunal wall 20 min after the feeding of [14C]chenodeoxycholate to bile fistula rats. It is suggested that these results complicate the interpretation of in vitro experiments on absorption of dihydroxy bile salts, and that they indicate that the human small intestine may be able to metabolize chenodeoxycholate."} {"id": "PMID:1278654", "title": "Jaundice in severe bacterial infection.", "content": "Thirty patients are described who developed jaundice during the course of severe bacterial infection. Although the infecting organism was variable, as was the site of infection, the patients were generally ill and pyrexial. The group had a very high mortality rate (43%). A positive blood culture was obtained in 11 patients. Biochemical abnormalities noted were those of an increased concentration of conjugated bilirubin in the serum with only a modest increase in alkaline phosphatase and transaminase levels. Serum cholesterol was found to be normal. The mean serum urea level was significantly elevated, as were creatine phosphokinase and lactic dehydrogenase. Most patients exhibited a neutrophil leukocytosis and an elevated sedimentation rate, and the mean hemoglobin level was low. Liver histology was studied in 13 patients. There was evidence of mild bile stasis in 5 and moderate bile stasis in 2. Findings were otherwise nonspecific and were characterized by fatty change and/or inflammatory cells in the portal areas. There was no correlation between degree or duration of juandice and prognosis, although all patients who died remained jaundiced until death. It is suggested that this syndrome is not one of true cholestasis in that all biliary substances were not shown to be elevated in the serum, but that it is rather a selective defect in the excretion of conjugated bilirubin.", "contents": "Jaundice in severe bacterial infection. Thirty patients are described who developed jaundice during the course of severe bacterial infection. Although the infecting organism was variable, as was the site of infection, the patients were generally ill and pyrexial. The group had a very high mortality rate (43%). A positive blood culture was obtained in 11 patients. Biochemical abnormalities noted were those of an increased concentration of conjugated bilirubin in the serum with only a modest increase in alkaline phosphatase and transaminase levels. Serum cholesterol was found to be normal. The mean serum urea level was significantly elevated, as were creatine phosphokinase and lactic dehydrogenase. Most patients exhibited a neutrophil leukocytosis and an elevated sedimentation rate, and the mean hemoglobin level was low. Liver histology was studied in 13 patients. There was evidence of mild bile stasis in 5 and moderate bile stasis in 2. Findings were otherwise nonspecific and were characterized by fatty change and/or inflammatory cells in the portal areas. There was no correlation between degree or duration of juandice and prognosis, although all patients who died remained jaundiced until death. It is suggested that this syndrome is not one of true cholestasis in that all biliary substances were not shown to be elevated in the serum, but that it is rather a selective defect in the excretion of conjugated bilirubin."} {"id": "PMID:1278655", "title": "Test for alcoholic cirrhosis by conversion of [14C]- or [13C]galactose to expired CO2.", "content": "After ingestion of galactose (10 g per m2) labeled with 14C or 13C, breath was collected from subjects at intervals for 4 hr followed by measurement of 14CO2 by liquid scintillation counting or of 13CO2 by mass spectrometry. Nine subjects without liver disease and 21 \"cirrhotic\" patients were tested with 14C; 8 control subjects and 4 patients with diagnosis of cirrhosis were tested with 13C. The mean rates of expiration of labeled CO2 by the patients with \"cirrhosis\" were one-third to one-half of mean normal rates during the first 90 min. The time of peak concentration of tracer CO2 for cirrhotic patients (150 to 180 min) was later than for normal subjects (90 to 120 min). There was distinctly greater separation between control and liver disease groups by test of 14CO2 radioactivity at 1 hr than by serum alkaline phosphatase, total bilirubin, and transaminase, but only slightly better separation than by serum albumin concentration (which was highly correlated with 14CO2 output). The [14C]galactose test is simpler than the standard intravenous galactose tolerance test, and , like the latter, appears superior to some other tests for recognition of cirrhosis. The use of 13C provides an example of a new direction for clinical application of this stable, nonradioactive nuclide.", "contents": "Test for alcoholic cirrhosis by conversion of [14C]- or [13C]galactose to expired CO2. After ingestion of galactose (10 g per m2) labeled with 14C or 13C, breath was collected from subjects at intervals for 4 hr followed by measurement of 14CO2 by liquid scintillation counting or of 13CO2 by mass spectrometry. Nine subjects without liver disease and 21 \"cirrhotic\" patients were tested with 14C; 8 control subjects and 4 patients with diagnosis of cirrhosis were tested with 13C. The mean rates of expiration of labeled CO2 by the patients with \"cirrhosis\" were one-third to one-half of mean normal rates during the first 90 min. The time of peak concentration of tracer CO2 for cirrhotic patients (150 to 180 min) was later than for normal subjects (90 to 120 min). There was distinctly greater separation between control and liver disease groups by test of 14CO2 radioactivity at 1 hr than by serum alkaline phosphatase, total bilirubin, and transaminase, but only slightly better separation than by serum albumin concentration (which was highly correlated with 14CO2 output). The [14C]galactose test is simpler than the standard intravenous galactose tolerance test, and , like the latter, appears superior to some other tests for recognition of cirrhosis. The use of 13C provides an example of a new direction for clinical application of this stable, nonradioactive nuclide."} {"id": "PMID:1278657", "title": "Studies on the development of endocrine glands in fishes. V. Development of the thyroid gland in two species of teleosts.", "content": "In Channa punctatus the thyroid anlage is seen 40 h after hatching and is recognized as cells aggregating in the form of follicles with no colloid. During subsequent stages of development the thyroid follicles increase in number and in 5 days old larva an active division of cells and many follicles in the form of epithelial cords are seen. In 2 months old juvenile fish several thyroid follicles and lymphatic vessels are seen enclosed by connective tissue capsule. In Clarias batrachus the thyroid anlage is seen as a group of cells around tiny colloid droplets and is situated just below the bifuration of the 1st branchial artery. This stage is seen in 60 h old larva and is developed into thyroid follicles which is a long chain along the jugular vein and ventral aorta during latter stages of development. It is concluded that during early larval period of these fishes, the thyroid cells begin to trap iodine from the blood and synthesize it in the form of thyroid hormone which is stored as colloid and is also liberated in blood stream simultaneously. The compact nature of the thyroid gland in C. punctatus is because of development of connective sheath around follicles during early stages.", "contents": "Studies on the development of endocrine glands in fishes. V. Development of the thyroid gland in two species of teleosts. In Channa punctatus the thyroid anlage is seen 40 h after hatching and is recognized as cells aggregating in the form of follicles with no colloid. During subsequent stages of development the thyroid follicles increase in number and in 5 days old larva an active division of cells and many follicles in the form of epithelial cords are seen. In 2 months old juvenile fish several thyroid follicles and lymphatic vessels are seen enclosed by connective tissue capsule. In Clarias batrachus the thyroid anlage is seen as a group of cells around tiny colloid droplets and is situated just below the bifuration of the 1st branchial artery. This stage is seen in 60 h old larva and is developed into thyroid follicles which is a long chain along the jugular vein and ventral aorta during latter stages of development. It is concluded that during early larval period of these fishes, the thyroid cells begin to trap iodine from the blood and synthesize it in the form of thyroid hormone which is stored as colloid and is also liberated in blood stream simultaneously. The compact nature of the thyroid gland in C. punctatus is because of development of connective sheath around follicles during early stages."} {"id": "PMID:1278658", "title": "[Altitude adaptation. Biological problems in the context of the environment].", "content": "The following part of the description of adaptation to high altitude describes the geographical specifities of the relevant regions of the world. There are several factors which require an adaptive answer, such as hypoxia, temperature, terrain, nutrition etc. The terms of genetically determined and of individual adaptation are discussed, with special consideration of a duration of settlement in the main altitude regions of about ten thousand years, as well as the principles of adaptation in general, including the phenomenon of maladaptation. The problem of adaptation of animals to high altitude is reviewed in short especially in regard to mammals. The differential fertility proves to be most important in the survival of a species in high altitude as well as the individual adaptability, is the fitness which makes high altitude tolerable to newcomers.", "contents": "[Altitude adaptation. Biological problems in the context of the environment]. The following part of the description of adaptation to high altitude describes the geographical specifities of the relevant regions of the world. There are several factors which require an adaptive answer, such as hypoxia, temperature, terrain, nutrition etc. The terms of genetically determined and of individual adaptation are discussed, with special consideration of a duration of settlement in the main altitude regions of about ten thousand years, as well as the principles of adaptation in general, including the phenomenon of maladaptation. The problem of adaptation of animals to high altitude is reviewed in short especially in regard to mammals. The differential fertility proves to be most important in the survival of a species in high altitude as well as the individual adaptability, is the fitness which makes high altitude tolerable to newcomers."} {"id": "PMID:1278659", "title": "[Results of cytologic examinations of the cervix in women under the age of thirty (author's transl)].", "content": "154 suspicious and positive findings for carcinoma in women between the ages of 18 and 30 were reported. Included here were 7 cases of invasive carcinoma, 57 cases of epithelial carcinoma, 8 cases of advanced dysplasia and 17 cases of dysplasia in beginning and intermediate stages. The findings from two gynecologic practices in which the physicians annually conducted a cytologic examination of the cervix on every woman, regardless of age, were studied in particular. In both of these practices, 64 of the 89 preliminary stages of carcinoma and carcinoma itself in this age group were discovered in this way. The total material came from 26 contributors. The participation on the part of the young women in both gynecologic practices was unexpectedly high (33% of all those patients receiving preventive examinations). The established practice of conducting cytologic cancer tests on the cervix uteri only after the age of 30 can no longer be justified. One possible causal factor for the increased morbidity and the earlier occurrence of the disease is the coincidence between genital infections and the increased occurrence of neoplasia of the cervix due to earlier onset of sexual activity. It is imperative that women be informed of the increased risks and that they be given the opportunity of a cervical cancer test even before the age of thirty.", "contents": "[Results of cytologic examinations of the cervix in women under the age of thirty (author's transl)]. 154 suspicious and positive findings for carcinoma in women between the ages of 18 and 30 were reported. Included here were 7 cases of invasive carcinoma, 57 cases of epithelial carcinoma, 8 cases of advanced dysplasia and 17 cases of dysplasia in beginning and intermediate stages. The findings from two gynecologic practices in which the physicians annually conducted a cytologic examination of the cervix on every woman, regardless of age, were studied in particular. In both of these practices, 64 of the 89 preliminary stages of carcinoma and carcinoma itself in this age group were discovered in this way. The total material came from 26 contributors. The participation on the part of the young women in both gynecologic practices was unexpectedly high (33% of all those patients receiving preventive examinations). The established practice of conducting cytologic cancer tests on the cervix uteri only after the age of 30 can no longer be justified. One possible causal factor for the increased morbidity and the earlier occurrence of the disease is the coincidence between genital infections and the increased occurrence of neoplasia of the cervix due to earlier onset of sexual activity. It is imperative that women be informed of the increased risks and that they be given the opportunity of a cervical cancer test even before the age of thirty."} {"id": "PMID:1278660", "title": "[The value of local application of a vasoconstrictive peptide during colposcopy (author's transl)].", "content": "The vasoconstrictive peptide (Ornithin-Vasopressin, experimental name POR 8) was tested regarding its usefulness in colposcopic diagnosis and differential diagnosis. In a concentration of 5 IE/2 ml of normal saline the compound resulted in good hemostasis in 88% of the cases. The differential diagnosis of the atypical transformation zone was much easier because of the difference in constriction between normal and abnormal vessels. The local application of \"POR 8\" is a valuable aid in the colposcopic diagnosis and differential diagnosis of the bleeding cervix in the cervix with an atypical transformation zone.", "contents": "[The value of local application of a vasoconstrictive peptide during colposcopy (author's transl)]. The vasoconstrictive peptide (Ornithin-Vasopressin, experimental name POR 8) was tested regarding its usefulness in colposcopic diagnosis and differential diagnosis. In a concentration of 5 IE/2 ml of normal saline the compound resulted in good hemostasis in 88% of the cases. The differential diagnosis of the atypical transformation zone was much easier because of the difference in constriction between normal and abnormal vessels. The local application of \"POR 8\" is a valuable aid in the colposcopic diagnosis and differential diagnosis of the bleeding cervix in the cervix with an atypical transformation zone."} {"id": "PMID:1278661", "title": "[Retroperitoneal diseases and geriatric-gynecologic laparatomy (author's transl)].", "content": "24 cases are described in which retroperitoneal processes were operated on for primarily gynecologic reasons in women of at least 60 years of age. They include 6 sarcomas, 3 neurinomas, 1 cyst, 1 fibroma, 1 lipoma, 1 congenital sacciform kidney, 1 hydronephrosis, 3 pancreatic carcinomas, 2 renal carcinomas, 1 ureteral cyst and 4 metastases of various malignomas. These cases were gathered in 18 West Berlin Departments of Obstetrics and Gynecology during a 10-year period. The post-operative mortality rate was 37.5% (9 deaths); this is probably due to the relatively low incidence of symptoms and signs associated with retroperitoneal diseases and their anatomical localization. Finally, new procedures for the diagnosis of retroperitoneal tumors are indicated.", "contents": "[Retroperitoneal diseases and geriatric-gynecologic laparatomy (author's transl)]. 24 cases are described in which retroperitoneal processes were operated on for primarily gynecologic reasons in women of at least 60 years of age. They include 6 sarcomas, 3 neurinomas, 1 cyst, 1 fibroma, 1 lipoma, 1 congenital sacciform kidney, 1 hydronephrosis, 3 pancreatic carcinomas, 2 renal carcinomas, 1 ureteral cyst and 4 metastases of various malignomas. These cases were gathered in 18 West Berlin Departments of Obstetrics and Gynecology during a 10-year period. The post-operative mortality rate was 37.5% (9 deaths); this is probably due to the relatively low incidence of symptoms and signs associated with retroperitoneal diseases and their anatomical localization. Finally, new procedures for the diagnosis of retroperitoneal tumors are indicated."} {"id": "PMID:1278662", "title": "[Investigation of HL-antigens in cervical cancer patients (author's transl)].", "content": "Twenty-three of HL-antigens were investigated in 119 patients with clinical cancer and 230 female controls. Patients with cervical carcioma showed significant differences of some HLA frequencies from that of the controls. HLA-A 3 and A 28 were increased, HLA-A 1 was decreased. HL-antigens could be factors, together with others yet unknown, which produce an increased susceptibility to the disease.", "contents": "[Investigation of HL-antigens in cervical cancer patients (author's transl)]. Twenty-three of HL-antigens were investigated in 119 patients with clinical cancer and 230 female controls. Patients with cervical carcioma showed significant differences of some HLA frequencies from that of the controls. HLA-A 3 and A 28 were increased, HLA-A 1 was decreased. HL-antigens could be factors, together with others yet unknown, which produce an increased susceptibility to the disease."} {"id": "PMID:1278663", "title": "[The frequency and causes of spontaneous abortion following artifitial insemination (author's transl)].", "content": "This paper is concerned with the causes of spontaneous abortion in a sample of 200 pregnancies induced by artificial insemination. In particular it examines the importance of the following factors: existing disorders in the woman's menstrual cycle, the influence of hormone treatment during the conception cycle, the age of the woman treated, and the type of semen used. Of the 200 pregnancies in our treatment sample 27 terminated in abortions (13.5%). Clinical examination before treatment established the presence of menstrual disorders in 69 of 180 women to be treated: 23.9% exhibited corpus luteum deficiency, 12% anovular cycles, and 2% oligomenorrhea. On the basis of this preliminary examination the principal cause of abortion proved to be an existing corpus luteum deficiency, since 15 of the 27 abortions occurred in women with this type of menstrual disorder. Our observations show that it is important when performing artificial insemination to correct the patient's existing menstrual disorders by means of hormone treatment. This emerges from the following figures: In 26 cases without hormone treatment the incidence of abortion was 35%. In 174 cases that received hormone treatment during the successful cycle only 18 abortions occurred (an incidence of 10.3%). Breaking down hormone treatment into 6 basic types, we get incidences of abortion ranging from 0 to 25% in the different groups. Dividing the treatment sample into age groups reveals an 11 to 14% incidence of abortion in the 30 to 34 age group; in the 35 to 40 group age group the incidence doubles to 26%. Whereas existing menstrual disorders and adequate hormone treatment significantly influence the incidence of abortion, there is no close relationship between incidence of abortion and the type of semen used. The innocuousness of using deep-frozen semen with an admixture of glycerine has been shown by various authors reporting on laboratory and clinical investigations. For 117 pregnancies induced purely with deep-frozen semen we had an incidence of abortion of 13.7%. This figure is of the same order as the incidence of abortion in pregnancies induced by insemination with fresh semen. The results obtained permit one to conclude that incidence of abortion is not significantly dependent on the type of semen used. Our work demonstrates the importance of assessing the patient's genital constitution from both the functional and the organic points of view, not merely in order to achieve conception but also for the purposes of preventing abortion by means of the appropriate hormone treatment. If satisfactory therapeutic results are to be achieved candidates for artificial insemination must therefore be given a thorough diagnostic examination beforehand and, if necessary, adequate hormone treatment during the insemination cycle.", "contents": "[The frequency and causes of spontaneous abortion following artifitial insemination (author's transl)]. This paper is concerned with the causes of spontaneous abortion in a sample of 200 pregnancies induced by artificial insemination. In particular it examines the importance of the following factors: existing disorders in the woman's menstrual cycle, the influence of hormone treatment during the conception cycle, the age of the woman treated, and the type of semen used. Of the 200 pregnancies in our treatment sample 27 terminated in abortions (13.5%). Clinical examination before treatment established the presence of menstrual disorders in 69 of 180 women to be treated: 23.9% exhibited corpus luteum deficiency, 12% anovular cycles, and 2% oligomenorrhea. On the basis of this preliminary examination the principal cause of abortion proved to be an existing corpus luteum deficiency, since 15 of the 27 abortions occurred in women with this type of menstrual disorder. Our observations show that it is important when performing artificial insemination to correct the patient's existing menstrual disorders by means of hormone treatment. This emerges from the following figures: In 26 cases without hormone treatment the incidence of abortion was 35%. In 174 cases that received hormone treatment during the successful cycle only 18 abortions occurred (an incidence of 10.3%). Breaking down hormone treatment into 6 basic types, we get incidences of abortion ranging from 0 to 25% in the different groups. Dividing the treatment sample into age groups reveals an 11 to 14% incidence of abortion in the 30 to 34 age group; in the 35 to 40 group age group the incidence doubles to 26%. Whereas existing menstrual disorders and adequate hormone treatment significantly influence the incidence of abortion, there is no close relationship between incidence of abortion and the type of semen used. The innocuousness of using deep-frozen semen with an admixture of glycerine has been shown by various authors reporting on laboratory and clinical investigations. For 117 pregnancies induced purely with deep-frozen semen we had an incidence of abortion of 13.7%. This figure is of the same order as the incidence of abortion in pregnancies induced by insemination with fresh semen. The results obtained permit one to conclude that incidence of abortion is not significantly dependent on the type of semen used. Our work demonstrates the importance of assessing the patient's genital constitution from both the functional and the organic points of view, not merely in order to achieve conception but also for the purposes of preventing abortion by means of the appropriate hormone treatment. If satisfactory therapeutic results are to be achieved candidates for artificial insemination must therefore be given a thorough diagnostic examination beforehand and, if necessary, adequate hormone treatment during the insemination cycle."} {"id": "PMID:1278664", "title": "[The frequency and clinical significance of incomplete removal of epithelial lesions on the cervix uteri by conisation (author's transl)].", "content": "In cone biopsies of 413 patients we found 394 cases with premalignant or malignant lesions of squamous epithelium. Judged by the examination of the margins of the cone biopsy specimens, the removal of these epithelial lesions was found to be complete in an average of 62,9%. The increasing degree of epithelial atypia correlated with an increasing rate of residual malignant or premalignant tissue. The operation was mostly not radical in the endocervix. In 154 cases subsequent hysterectomia was performed. In 22% of the cases in which the margins of the cone biopsy specimens were free of epithelial changes, residual atypia was discovered in the uterus. On the contrary, in 35% of patients in which residual epithelial atypia was suspected, the uterus was found to be free of malignancy. The reasons are discussed. It is emphasized to pay attention to radical excision especially in the endocervix. Follow-up and smear controls are also necessary when margins of cone biopsy specimen are free of epithelial atypia. In young females desiring further pregnancies, treatment can be left at conisation even if it was not radical; frequent smear controls are obligatory in these cases.", "contents": "[The frequency and clinical significance of incomplete removal of epithelial lesions on the cervix uteri by conisation (author's transl)]. In cone biopsies of 413 patients we found 394 cases with premalignant or malignant lesions of squamous epithelium. Judged by the examination of the margins of the cone biopsy specimens, the removal of these epithelial lesions was found to be complete in an average of 62,9%. The increasing degree of epithelial atypia correlated with an increasing rate of residual malignant or premalignant tissue. The operation was mostly not radical in the endocervix. In 154 cases subsequent hysterectomia was performed. In 22% of the cases in which the margins of the cone biopsy specimens were free of epithelial changes, residual atypia was discovered in the uterus. On the contrary, in 35% of patients in which residual epithelial atypia was suspected, the uterus was found to be free of malignancy. The reasons are discussed. It is emphasized to pay attention to radical excision especially in the endocervix. Follow-up and smear controls are also necessary when margins of cone biopsy specimen are free of epithelial atypia. In young females desiring further pregnancies, treatment can be left at conisation even if it was not radical; frequent smear controls are obligatory in these cases."} {"id": "PMID:1278665", "title": "[Massive bleeding from a ruptured corpus luteum (author's transl)].", "content": "A case is demonstrated, where a 37-year old patient who was continuously dialyzed due to bilateral renal insufficiency, developed an acute and severe bleeding from a ruptured Graafian follicle. The bleeding was life-threatening, most likely due to the continuous treatment with heparin (up to 30,000 IU/day) needed for hemodialysis procedure. Differential diagnostic considerations and treatment measures are reported.", "contents": "[Massive bleeding from a ruptured corpus luteum (author's transl)]. A case is demonstrated, where a 37-year old patient who was continuously dialyzed due to bilateral renal insufficiency, developed an acute and severe bleeding from a ruptured Graafian follicle. The bleeding was life-threatening, most likely due to the continuous treatment with heparin (up to 30,000 IU/day) needed for hemodialysis procedure. Differential diagnostic considerations and treatment measures are reported."} {"id": "PMID:1278690", "title": "When seizures are complicated by coma.", "content": "Convulsions in elderly patients result from systemic biochemical or focal structural processes. These patients require a thorough evaluation, because idiopathic seizures are virtually unknown in this age group. Marginal circulatory and pulmonary function compromises central nervous system function, which can result in prolonged postictal coma. Furthermore, the patient's fragility can coma. Furthermore, the patient's fragility can complicate anticonvulsant therapy. The physician must be prepared to support the patient in prolonged postictal coma, since many patients can recover the preictal level of function.", "contents": "When seizures are complicated by coma. Convulsions in elderly patients result from systemic biochemical or focal structural processes. These patients require a thorough evaluation, because idiopathic seizures are virtually unknown in this age group. Marginal circulatory and pulmonary function compromises central nervous system function, which can result in prolonged postictal coma. Furthermore, the patient's fragility can coma. Furthermore, the patient's fragility can complicate anticonvulsant therapy. The physician must be prepared to support the patient in prolonged postictal coma, since many patients can recover the preictal level of function."} {"id": "PMID:1278698", "title": "Finding medical reasons for psychiatric behavior.", "content": "Medical disease was the cause of the primary disability in the majority (61.2 percent) of 116 elderly psychiatric patients treated at Bellevue Hospital Center. A change in behavior signaled the onset of medical illness with acute brain syndrome. The history that documented a change in behavior was derived from sources other than the patient. It is important to obtain such history during admission evaluation of elderly persons who are confused or whose memory is impaired. Multidiciplinary services enabled many patients to improve so that they could return home rather than being institutionalized. Had such services been available before their admission, many patients might have avoided hospitalization. As a result of this study, the geriatrics unit at Bellevue Hospital Center began to devote its efforts to elderly persons in the community.", "contents": "Finding medical reasons for psychiatric behavior. Medical disease was the cause of the primary disability in the majority (61.2 percent) of 116 elderly psychiatric patients treated at Bellevue Hospital Center. A change in behavior signaled the onset of medical illness with acute brain syndrome. The history that documented a change in behavior was derived from sources other than the patient. It is important to obtain such history during admission evaluation of elderly persons who are confused or whose memory is impaired. Multidiciplinary services enabled many patients to improve so that they could return home rather than being institutionalized. Had such services been available before their admission, many patients might have avoided hospitalization. As a result of this study, the geriatrics unit at Bellevue Hospital Center began to devote its efforts to elderly persons in the community."} {"id": "PMID:1278708", "title": "Growth of the pig: changes in red cell and plasma volumes.", "content": "In the pig, plasma volume increased from 58.0 +/- 2.53 ml/kg on day 1 to 66.7 +/- 3.35 (P less than 0.05) on day 2, and decreased between days 7 and 9 to 56.4 +/- 1.16 (P less than 0.02). The next significant change in volume occurred at weaning: from 53.1 +/- 1.24 ml/kg at week 4 to 44.16 +/- 2.2 at week 5. It then increased to 56.1 +/- 1.41 ml/kg by week 7 and decreased to 48.5 +/- 1.44 by week 9; then between weeks 10 and 11 it increased to 59.33 +/- 3.01 (P less than 0.005). Red cell volume on day 1 was 32.3 +/- 1.25 ml/kg and decreased to 20.2 +/- 1.37 (P less than 0.01) on day 2. The only other change of significance in red cell volume over the 12-week growth period was a small increasan 0.05) at week 6. The mean for BVRcells was 0.88 +/- 0.01 for the growth period. The pattern of changes in plasma and red cell volumes differed from those for the beagle.", "contents": "Growth of the pig: changes in red cell and plasma volumes. In the pig, plasma volume increased from 58.0 +/- 2.53 ml/kg on day 1 to 66.7 +/- 3.35 (P less than 0.05) on day 2, and decreased between days 7 and 9 to 56.4 +/- 1.16 (P less than 0.02). The next significant change in volume occurred at weaning: from 53.1 +/- 1.24 ml/kg at week 4 to 44.16 +/- 2.2 at week 5. It then increased to 56.1 +/- 1.41 ml/kg by week 7 and decreased to 48.5 +/- 1.44 by week 9; then between weeks 10 and 11 it increased to 59.33 +/- 3.01 (P less than 0.005). Red cell volume on day 1 was 32.3 +/- 1.25 ml/kg and decreased to 20.2 +/- 1.37 (P less than 0.01) on day 2. The only other change of significance in red cell volume over the 12-week growth period was a small increasan 0.05) at week 6. The mean for BVRcells was 0.88 +/- 0.01 for the growth period. The pattern of changes in plasma and red cell volumes differed from those for the beagle."} {"id": "PMID:1278709", "title": "Skeletal muscle cellularity in mice selected for large body size and in controls.", "content": "Body composition and skeletal muscle weights, fiber diameters, fiber numbers, and RNA and DNA concentrations were studied in mice selected for large body size (GLW) compared to an unselected control (C) line. At 60 days of age, body weight of GLW mice was 70 to 75% greater than C mice, but % body water, fat or dry fat-free residue did not differ between the lines. In both GLW and C mice, greater muscle weight in males compared to females was due to larger diameter fibers and not to significant differences in fiber number between sexes, although in most cases, males had slightly higher mean fiber number. Fiber diameters were similar in the two lines and the greater muscle weights of GLW mice were due to more fibers than in the muscles of C mice. RNA and DNA concentrations were slightly, but not significantly, higher in GLW skeletal muscles.", "contents": "Skeletal muscle cellularity in mice selected for large body size and in controls. Body composition and skeletal muscle weights, fiber diameters, fiber numbers, and RNA and DNA concentrations were studied in mice selected for large body size (GLW) compared to an unselected control (C) line. At 60 days of age, body weight of GLW mice was 70 to 75% greater than C mice, but % body water, fat or dry fat-free residue did not differ between the lines. In both GLW and C mice, greater muscle weight in males compared to females was due to larger diameter fibers and not to significant differences in fiber number between sexes, although in most cases, males had slightly higher mean fiber number. Fiber diameters were similar in the two lines and the greater muscle weights of GLW mice were due to more fibers than in the muscles of C mice. RNA and DNA concentrations were slightly, but not significantly, higher in GLW skeletal muscles."} {"id": "PMID:1278710", "title": "Relationship between red cell mass, body weight, lean body mass, and body cell mass in growing pigs and beagles.", "content": "During growth in 55 pigs (from birth through week 12) and 42 beagles studied (from birth through year 1), there was an equally close association between red cell mass (RCM) and body weight, lean body mass (LBM) and body cell mass (BCM); the coefficients of correlation were between 0.94-0.99. The association of RCM with body weight was the result of BCM, extracellular tissue (ECT), and fat, each increasing at a constant rate relative to body weight. The primary relationship appears to be between RCM, the oxygen-delivery system, and BCM, the principla oxygen-using system; and the close association of RCM with body weight and LBM the results of the growth patterns of their components.", "contents": "Relationship between red cell mass, body weight, lean body mass, and body cell mass in growing pigs and beagles. During growth in 55 pigs (from birth through week 12) and 42 beagles studied (from birth through year 1), there was an equally close association between red cell mass (RCM) and body weight, lean body mass (LBM) and body cell mass (BCM); the coefficients of correlation were between 0.94-0.99. The association of RCM with body weight was the result of BCM, extracellular tissue (ECT), and fat, each increasing at a constant rate relative to body weight. The primary relationship appears to be between RCM, the oxygen-delivery system, and BCM, the principla oxygen-using system; and the close association of RCM with body weight and LBM the results of the growth patterns of their components."} {"id": "PMID:1278711", "title": "Effects of cytochalasin B on the morphogenesis of explanted early chick embryos.", "content": "Effects of cytochalasin B (CB) on chick embryos explanted at stages 4-5 and cultured for 24 hours were studied. CB (2-4 mug/ml) inhibited blastodermal expansion and neural tube closure in over 90% of the embryos. Somite formation was inhibited only where neural tissue was very degenerate. The development of other structures was usually unaffected. Cellular degeneration occurred in severely affected neuroepithelium, but cells at various phases of mitosis were found throughout its thickness, suggesting that interkinetic nuclear migration had been inhibited. Electron microscopic studies of the flattened neural tube showed that CB disrupted microfilaments and reduced the number of cytoplasmic extensions, but had no apparent effect on microtubules and other organelles. These effects were reversible. Futhermore, dimethyl sulfoxide, at 0.2-0.4% (concentrations present in 2-4 mug/ml CB medium), had no adverse effect, indicating that the observed abnormalities were direct consequences of CB treatment.", "contents": "Effects of cytochalasin B on the morphogenesis of explanted early chick embryos. Effects of cytochalasin B (CB) on chick embryos explanted at stages 4-5 and cultured for 24 hours were studied. CB (2-4 mug/ml) inhibited blastodermal expansion and neural tube closure in over 90% of the embryos. Somite formation was inhibited only where neural tissue was very degenerate. The development of other structures was usually unaffected. Cellular degeneration occurred in severely affected neuroepithelium, but cells at various phases of mitosis were found throughout its thickness, suggesting that interkinetic nuclear migration had been inhibited. Electron microscopic studies of the flattened neural tube showed that CB disrupted microfilaments and reduced the number of cytoplasmic extensions, but had no apparent effect on microtubules and other organelles. These effects were reversible. Futhermore, dimethyl sulfoxide, at 0.2-0.4% (concentrations present in 2-4 mug/ml CB medium), had no adverse effect, indicating that the observed abnormalities were direct consequences of CB treatment."} {"id": "PMID:1278712", "title": "Chemotherapy on Harding-Passey melanoma with gladenine. Part I.", "content": "The effect of Gladenine, an oncolytic antibiotic produced by a newly discovered fungus, Paecilomyces todicus, nov. sp. was investigated on Harding-Passey, hard tumor, melanoma. A long-term screening technique was used in the investigation. 15 mg/100 gm. wt/mouse was injected I.P. starting 10-14 days after transplant, when all tumors were well pronounced, and continuing for 18-34 days. The majority of mice did not lose weight. Tumors were absent on the average in about 33% of the mice and average T/C was .16. Combining Cladenine with Hydrazine sulfate, either 1.5 mg. or 2.5 mg./100 gm. wt./mouse, using the same screening technique, resulted in 60-100% of mice free of tumors, and still remaining so several months later. Average T/C was .06. Combined therapy with Gladenine and Hydrazine sulfate at 3.75 mg./100 gm. wt./mouse gave less satisfactory results. Repeated screening tests using the same long term techniques, gave similar or identical results. It appears that Harding-Passey melanoma is susceptible to the chemotherapy of Gladenine alone and/or combined with small doses of Hydrazine sulfate.", "contents": "Chemotherapy on Harding-Passey melanoma with gladenine. Part I. The effect of Gladenine, an oncolytic antibiotic produced by a newly discovered fungus, Paecilomyces todicus, nov. sp. was investigated on Harding-Passey, hard tumor, melanoma. A long-term screening technique was used in the investigation. 15 mg/100 gm. wt/mouse was injected I.P. starting 10-14 days after transplant, when all tumors were well pronounced, and continuing for 18-34 days. The majority of mice did not lose weight. Tumors were absent on the average in about 33% of the mice and average T/C was .16. Combining Cladenine with Hydrazine sulfate, either 1.5 mg. or 2.5 mg./100 gm. wt./mouse, using the same screening technique, resulted in 60-100% of mice free of tumors, and still remaining so several months later. Average T/C was .06. Combined therapy with Gladenine and Hydrazine sulfate at 3.75 mg./100 gm. wt./mouse gave less satisfactory results. Repeated screening tests using the same long term techniques, gave similar or identical results. It appears that Harding-Passey melanoma is susceptible to the chemotherapy of Gladenine alone and/or combined with small doses of Hydrazine sulfate."} {"id": "PMID:1278713", "title": "Hand skeletal development among Ecuadorians living under conditions of iodine deficiency and endemic goiter.", "content": "Hand radiographic assessment has revealed the pattern of skeletal growth and maturation among Ecuadorian Indian villagers where iodine deficiency has resulted in an endemia of goiter and cretinism. This is intended to provide base line information for future attempts to learn about physical impairment among people living under inadequate iodine nutriture.", "contents": "Hand skeletal development among Ecuadorians living under conditions of iodine deficiency and endemic goiter. Hand radiographic assessment has revealed the pattern of skeletal growth and maturation among Ecuadorian Indian villagers where iodine deficiency has resulted in an endemia of goiter and cretinism. This is intended to provide base line information for future attempts to learn about physical impairment among people living under inadequate iodine nutriture."} {"id": "PMID:1278714", "title": "Model for initial vascular patterns in melanoma transplants.", "content": "In this paper we present a simple mathematical model that adequately accounts for at least the initial vasculature that is established in a melanoma transplant. It is assumed that the tumor produces a substance (tumor angiogenesis factor--TAF) that elicits capillary sprouts from the vascular bed of the host. These sprouts then invade the tumor along the gradient of TAF and cross-connect forming a vascular pathway that is similar to the experimental patterns observed in a hamster cheek pouch. This model is then extended to include the migration of loops. The rupture and formation of sprouts from these loops is assumed to depend on the strength of the stimulus (TAF). Under the assumption that the production of TAF is significantly reduced in a neighborhood of an established vessel, the network formed by the vessels in the tumor corresponds to the observed arboreal patterns.", "contents": "Model for initial vascular patterns in melanoma transplants. In this paper we present a simple mathematical model that adequately accounts for at least the initial vasculature that is established in a melanoma transplant. It is assumed that the tumor produces a substance (tumor angiogenesis factor--TAF) that elicits capillary sprouts from the vascular bed of the host. These sprouts then invade the tumor along the gradient of TAF and cross-connect forming a vascular pathway that is similar to the experimental patterns observed in a hamster cheek pouch. This model is then extended to include the migration of loops. The rupture and formation of sprouts from these loops is assumed to depend on the strength of the stimulus (TAF). Under the assumption that the production of TAF is significantly reduced in a neighborhood of an established vessel, the network formed by the vessels in the tumor corresponds to the observed arboreal patterns."} {"id": "PMID:1278715", "title": "Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis.", "content": "The frequency of HLA-A3 and HLA-B14 antigens was significantly higher in a series of 51 patients with idiopathic haemochromatosis than in a control group, being respectively 78-4 versus 27-0% and 25-5 versus 3-4%. This finding strongly supports the suggestion that idiopathic haemochromatosis is a genetic disease and suggests that the gene(s) responsible for the disease may be linked to the histocompatibility genes.", "contents": "Association of HLA-A3 and HLA-B14 antigens with idiopathic haemochromatosis. The frequency of HLA-A3 and HLA-B14 antigens was significantly higher in a series of 51 patients with idiopathic haemochromatosis than in a control group, being respectively 78-4 versus 27-0% and 25-5 versus 3-4%. This finding strongly supports the suggestion that idiopathic haemochromatosis is a genetic disease and suggests that the gene(s) responsible for the disease may be linked to the histocompatibility genes."} {"id": "PMID:1278716", "title": "Effect of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome.", "content": "The influence of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome was studied in 29 patients. After a period on a normal diet (10 MJ) an intravenous infusion of 40% glucose (8-4 MJ) together with a 1-6 MJ oral diet for two days resulted in an increment in plasma bilirubin concentration of 127 +/- 18% (mean +/- SEM) above the basal level. Both the administration of intravenous Intralipid 20% and the return to a normal diet caused a prompt reversal of this glucose effect. An increment of 135 +/- 10% in plasma bilirubin concentration was obtained when a standard \"fasting\" diet (1-6 MJ) was given for two days. When the lipid content of this \"fasting\" diet was increased from 33% to 85%, the rise in plasma bilirubin was only 49 +/- 19%. A 10 MJ oral diet for three days, which contained most of its energy content as carbohydrate and only 0-6% as lipid, produced a 76 +/- 12% increase in plasma bilirubin concentration. When the lipid content of the diet was increased to 9% of the energy intake no significant change from the basal level was observed. These findings support the hypothesis that the hyperbilirubinaemia associated with both carbohydrate feeding and fasting is attributable, at least in part, to lipid withdrawal. Although a restricted dietary intake or the parenteral administration of lipid-free solutions has a marked effect on the hyperbilirubinaemia of patients with Gilbert's syndrome, normal daily variation in dietary composition is unlikely to cause a significant change. The influence of different feeding regimes on neonatal hyperbilirubinaemia requires investigation.", "contents": "Effect of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome. The influence of dietary composition on the unconjugated hyperbilirubinaemia of Gilbert's syndrome was studied in 29 patients. After a period on a normal diet (10 MJ) an intravenous infusion of 40% glucose (8-4 MJ) together with a 1-6 MJ oral diet for two days resulted in an increment in plasma bilirubin concentration of 127 +/- 18% (mean +/- SEM) above the basal level. Both the administration of intravenous Intralipid 20% and the return to a normal diet caused a prompt reversal of this glucose effect. An increment of 135 +/- 10% in plasma bilirubin concentration was obtained when a standard \"fasting\" diet (1-6 MJ) was given for two days. When the lipid content of this \"fasting\" diet was increased from 33% to 85%, the rise in plasma bilirubin was only 49 +/- 19%. A 10 MJ oral diet for three days, which contained most of its energy content as carbohydrate and only 0-6% as lipid, produced a 76 +/- 12% increase in plasma bilirubin concentration. When the lipid content of the diet was increased to 9% of the energy intake no significant change from the basal level was observed. These findings support the hypothesis that the hyperbilirubinaemia associated with both carbohydrate feeding and fasting is attributable, at least in part, to lipid withdrawal. Although a restricted dietary intake or the parenteral administration of lipid-free solutions has a marked effect on the hyperbilirubinaemia of patients with Gilbert's syndrome, normal daily variation in dietary composition is unlikely to cause a significant change. The influence of different feeding regimes on neonatal hyperbilirubinaemia requires investigation."} {"id": "PMID:1278717", "title": "Altered elimination of antipyrine in patients with acute viral hepatitis.", "content": "The plasma half-life and clearance of antipyrine was investigated in patients during the acute phase and again during the recovery phase of viral hepatitis. Each patient served as his own control, thereby eliminating genetic factors and minimising environmental factors that cause large interindividual variations in antipyrine elimination rates. Liver function tests, antipyrine, half-life, plasma clearance, and the apparent volume of distribution were determined in the acute and recovery period. It was found that the appaarent volume of distribution of antipyrine did not change in five of six patients as they recovered. Five of the six patients showed prolonged plasma half-lives and decreased plasma clearance of the drug at the time of acute illness and these parameters reached normal values during recovery. The plasma half-life and clearance of the drug did not correlate with biochemical indices of liver function in the recovery phase. This demonstration supports the concept that drug metabolism is frequently impaired in liver disease.", "contents": "Altered elimination of antipyrine in patients with acute viral hepatitis. The plasma half-life and clearance of antipyrine was investigated in patients during the acute phase and again during the recovery phase of viral hepatitis. Each patient served as his own control, thereby eliminating genetic factors and minimising environmental factors that cause large interindividual variations in antipyrine elimination rates. Liver function tests, antipyrine, half-life, plasma clearance, and the apparent volume of distribution were determined in the acute and recovery period. It was found that the appaarent volume of distribution of antipyrine did not change in five of six patients as they recovered. Five of the six patients showed prolonged plasma half-lives and decreased plasma clearance of the drug at the time of acute illness and these parameters reached normal values during recovery. The plasma half-life and clearance of the drug did not correlate with biochemical indices of liver function in the recovery phase. This demonstration supports the concept that drug metabolism is frequently impaired in liver disease."} {"id": "PMID:1278718", "title": "Effect of diazepam and hyoscine butylbromide on response to secretin and cholecystokinin-pancreozymin in man.", "content": "Ten subjects received secretin and cholecystokinin or, in duplicate tests, the two hormones together with either diazepam or diazepam plus hyoscine butylbromide in order to determine whether these drugs, which are often used during retrograde endoscopic cannulation of the pancreatic duct, affect pancreatic and biliary secretion in response to the hormones. Diazepam with hyoscine butylbromide reduced the secretion of trypsin into the duodenum and delayed the appearance of both trypsin and bilirubin in duodenal aspirate. These effects must be taken into account when interpreting pancreatic and biliary responses measured during direct cannulation of the pancreatic duct.", "contents": "Effect of diazepam and hyoscine butylbromide on response to secretin and cholecystokinin-pancreozymin in man. Ten subjects received secretin and cholecystokinin or, in duplicate tests, the two hormones together with either diazepam or diazepam plus hyoscine butylbromide in order to determine whether these drugs, which are often used during retrograde endoscopic cannulation of the pancreatic duct, affect pancreatic and biliary secretion in response to the hormones. Diazepam with hyoscine butylbromide reduced the secretion of trypsin into the duodenum and delayed the appearance of both trypsin and bilirubin in duodenal aspirate. These effects must be taken into account when interpreting pancreatic and biliary responses measured during direct cannulation of the pancreatic duct."} {"id": "PMID:1278719", "title": "Small intestinal permeability. 1. Effects of ischaemia and exposure to acetyl salicylate.", "content": "Permeability of the small intestinal mucosa was estimated using a perfusion technique after either a period of ischaemia or exposure to acetyl salicylate. It was shown that these procedures increased the passive permeability of the mucosa to macromolecules while maintaining normal mucosal selectivity. Histologically, there was derangment of the epithelial cell layer of the villous tips without damage to the epithelial basement membrane or subepithelial structures. It is concluded that the epithelial cell layer is purely limiting with no selective function and that the role of selectivity must be ascribed to either or both of the other mucosal barriers, the capillary and the epithelial basement membrane.", "contents": "Small intestinal permeability. 1. Effects of ischaemia and exposure to acetyl salicylate. Permeability of the small intestinal mucosa was estimated using a perfusion technique after either a period of ischaemia or exposure to acetyl salicylate. It was shown that these procedures increased the passive permeability of the mucosa to macromolecules while maintaining normal mucosal selectivity. Histologically, there was derangment of the epithelial cell layer of the villous tips without damage to the epithelial basement membrane or subepithelial structures. It is concluded that the epithelial cell layer is purely limiting with no selective function and that the role of selectivity must be ascribed to either or both of the other mucosal barriers, the capillary and the epithelial basement membrane."} {"id": "PMID:1278720", "title": "Effects of 13-nle-motilin on the electrical and mechanical activity of the isolated perfused canine stomach and duodenum.", "content": "Synthetic 13-norleucine-motilin (13-nle-motilin), structural and biological analogue of the naturally-occurring duodenal polypeptide, motilin, is known to stimulate antral and duodenal motor activity in vitro, but delays gastric emptying in man. In this study the direct actions of the synthetic polypeptide on myoelectrical activity and intraluminal pressure have been studied in the isolated vascular-perfused canine stomach and duodenum. 13-nle-motilin increased intraluminal pressure in the pylorus and duodenum, and dose-response analysis showed the duodenum to be twice as sensitive as the pylorus to the polypeptide. Pressure changes in the antrum were small and not dose-related, but, whereas the basic electrical rhythm in the duodenum was not altered, slow wave frequency, rhythm, and propagation in the antrum were disturbed. Electronic analysis of the duodenal spike increase which accompanied pressure rises demonstrated correlations between increases in spikes, intraluminal pressure, and dose. These results show that the direct effect of the polypeptide on adjacent organs may explain the combination of increased motor activity with delayed gastric emptying as a consequence of disturbance in the co-ordination between antrum, pylorus, and duodenum.", "contents": "Effects of 13-nle-motilin on the electrical and mechanical activity of the isolated perfused canine stomach and duodenum. Synthetic 13-norleucine-motilin (13-nle-motilin), structural and biological analogue of the naturally-occurring duodenal polypeptide, motilin, is known to stimulate antral and duodenal motor activity in vitro, but delays gastric emptying in man. In this study the direct actions of the synthetic polypeptide on myoelectrical activity and intraluminal pressure have been studied in the isolated vascular-perfused canine stomach and duodenum. 13-nle-motilin increased intraluminal pressure in the pylorus and duodenum, and dose-response analysis showed the duodenum to be twice as sensitive as the pylorus to the polypeptide. Pressure changes in the antrum were small and not dose-related, but, whereas the basic electrical rhythm in the duodenum was not altered, slow wave frequency, rhythm, and propagation in the antrum were disturbed. Electronic analysis of the duodenal spike increase which accompanied pressure rises demonstrated correlations between increases in spikes, intraluminal pressure, and dose. These results show that the direct effect of the polypeptide on adjacent organs may explain the combination of increased motor activity with delayed gastric emptying as a consequence of disturbance in the co-ordination between antrum, pylorus, and duodenum."} {"id": "PMID:1278721", "title": "Serum pyridoxal in patients with gastric pathology.", "content": "Fasting serum pyridoxal was assayed by an automated microbiological system in 60 patients investigated for dyspepsia, patients with active peptic ulceration being excluded from the study. Gastritis was present in 30 patients, gastric carcinoma in 16, six patients had benign polyps, and, in eight patients, radiology, endoscopy, and biopsy failed to shown any abnormality. Of the 52 patients with gastric pathology, 44 had a low serum pyridoxal.", "contents": "Serum pyridoxal in patients with gastric pathology. Fasting serum pyridoxal was assayed by an automated microbiological system in 60 patients investigated for dyspepsia, patients with active peptic ulceration being excluded from the study. Gastritis was present in 30 patients, gastric carcinoma in 16, six patients had benign polyps, and, in eight patients, radiology, endoscopy, and biopsy failed to shown any abnormality. Of the 52 patients with gastric pathology, 44 had a low serum pyridoxal."} {"id": "PMID:1278722", "title": "Evaluation of specific value of endoscopic biopsies and brush cytology for malignancies of the oesophagus and stomach.", "content": "The value of multiple biopsies and brush cytology at oesophago-gastroscopy was assessed in relation to macroscopy and localization on 100 verified tumours in a prospective study. The cumulative accuracy achieved was 96%. This was significantly better (P less than 0-01) than that of biopsy (83%) and of cytology (85%). While the reliability of both procedures was not significantly different in malignancies of the oesophagus, the gastric body, and the antrum, cytoloty was significantly more accurate in cancers of the cardia (90% and 55% respectively, P less than 0-05). Cytology was also more reliable in stenosing tumours (92%/72%,P less than 0-05). In polypoid malignancies a positive but not significant trend was found in favour of multiple biopsies (94%/64%). One of the two early cancers was only diagnosed by cytology. The results confirm the high diagnostic accuracy of multiple endoscopic biopsies combined with brush cytology and demonstrate the value of cytology in stenosing tumours, especially in those of the cardia.", "contents": "Evaluation of specific value of endoscopic biopsies and brush cytology for malignancies of the oesophagus and stomach. The value of multiple biopsies and brush cytology at oesophago-gastroscopy was assessed in relation to macroscopy and localization on 100 verified tumours in a prospective study. The cumulative accuracy achieved was 96%. This was significantly better (P less than 0-01) than that of biopsy (83%) and of cytology (85%). While the reliability of both procedures was not significantly different in malignancies of the oesophagus, the gastric body, and the antrum, cytoloty was significantly more accurate in cancers of the cardia (90% and 55% respectively, P less than 0-05). Cytology was also more reliable in stenosing tumours (92%/72%,P less than 0-05). In polypoid malignancies a positive but not significant trend was found in favour of multiple biopsies (94%/64%). One of the two early cancers was only diagnosed by cytology. The results confirm the high diagnostic accuracy of multiple endoscopic biopsies combined with brush cytology and demonstrate the value of cytology in stenosing tumours, especially in those of the cardia."} {"id": "PMID:1278816", "title": "Capillariids (Nematoda: Capillariidae) from passeriform birds of Nepal).", "content": "A total of 83 hosts of the order Passeriformes from Nepal were examined for nematodes. Nine of them were found to be infected with 4 nematode species, Capillaria exilis, C. ovopunctata, Capillaria sp. and Thominx rigidula. The last species is redescribed in detail. Three of the definitive hosts are new for the above-mentioned nematode species and this is the first recorded from Nepal.", "contents": "Capillariids (Nematoda: Capillariidae) from passeriform birds of Nepal). A total of 83 hosts of the order Passeriformes from Nepal were examined for nematodes. Nine of them were found to be infected with 4 nematode species, Capillaria exilis, C. ovopunctata, Capillaria sp. and Thominx rigidula. The last species is redescribed in detail. Three of the definitive hosts are new for the above-mentioned nematode species and this is the first recorded from Nepal."} {"id": "PMID:1278817", "title": "Variability of hard parts of opisthaptor of two species of Gyrodactylus nordmann, 1832 (Monogenoidea) from Phoxinus Phoxinus (L.).", "content": "The morphological and metrical variability of hard parts of opisthaptor was studied in the representatives of local populations of Gyrodactylus aphyae Malmberg, 1957 and G. macronychus Malmberg, 1957. The changes within the range of variability, which were observed during the year, correspond to regular and periodical changes in the environmental temperatures. The hard parts of opisthaptor were much smaller in specimens occurring during warm seasons than in specimens occurring during cold seasons. The temperature of about 8 degrees C forms a boundary between warm and cold seasons. The author assumes that similarly as G. aphyae and G. macronychus also other members of the genus Gyrodactylus living in climatic zones with regular change of seasons will react similarly on the annual variation in the environmental temperatures.", "contents": "Variability of hard parts of opisthaptor of two species of Gyrodactylus nordmann, 1832 (Monogenoidea) from Phoxinus Phoxinus (L.). The morphological and metrical variability of hard parts of opisthaptor was studied in the representatives of local populations of Gyrodactylus aphyae Malmberg, 1957 and G. macronychus Malmberg, 1957. The changes within the range of variability, which were observed during the year, correspond to regular and periodical changes in the environmental temperatures. The hard parts of opisthaptor were much smaller in specimens occurring during warm seasons than in specimens occurring during cold seasons. The temperature of about 8 degrees C forms a boundary between warm and cold seasons. The author assumes that similarly as G. aphyae and G. macronychus also other members of the genus Gyrodactylus living in climatic zones with regular change of seasons will react similarly on the annual variation in the environmental temperatures."} {"id": "PMID:1278818", "title": "Cestodes of ruminants in Afghanistan.", "content": "Five cestode species parasitizing ruminants were found for the first time in Afghanistan: Moniezia benedeni, M. expansa, Avitellina centripunctata, Stilesia globipunctata, and Thysaniezia giardi.", "contents": "Cestodes of ruminants in Afghanistan. Five cestode species parasitizing ruminants were found for the first time in Afghanistan: Moniezia benedeni, M. expansa, Avitellina centripunctata, Stilesia globipunctata, and Thysaniezia giardi."} {"id": "PMID:1278819", "title": "Morphological and histochemical demonstration of hooks in the rostellar region of Cysticercus bovis.", "content": "Hooklets and early developmental stages of hooks were discovered in the tegument among the microtriches in the rostellar region of 83- and 108-day-old Cysticercus bovis. The cortical layer of hooks consists of proteins with tyrosine and SS groups. The rostellar sac and bulb are distinctly developed in the parenchyma of the rostellar region.", "contents": "Morphological and histochemical demonstration of hooks in the rostellar region of Cysticercus bovis. Hooklets and early developmental stages of hooks were discovered in the tegument among the microtriches in the rostellar region of 83- and 108-day-old Cysticercus bovis. The cortical layer of hooks consists of proteins with tyrosine and SS groups. The rostellar sac and bulb are distinctly developed in the parenchyma of the rostellar region."} {"id": "PMID:1278820", "title": "Contribution to the knowledge of synanthropic flies in the Mongolian People's Republic.", "content": "A survey is given of 23 species of synathropic and synbovine Diptera collected in the years 1968, 1969 and 1972 in the Mongolian People's Republic by J. Min\u00e1r. Besides the faunistical comments, the species of hygienic-epidemiological or public health importance are discussed.", "contents": "Contribution to the knowledge of synanthropic flies in the Mongolian People's Republic. A survey is given of 23 species of synathropic and synbovine Diptera collected in the years 1968, 1969 and 1972 in the Mongolian People's Republic by J. Min\u00e1r. Besides the faunistical comments, the species of hygienic-epidemiological or public health importance are discussed."} {"id": "PMID:1278821", "title": "First record of a cyclopoid host-Mesocyclops leuckarti (Claus) for an acanthocephalous worm-Acanthosentis dattai Podder from Delhi (India).", "content": "Among seven species of Cyclops encountered in four water ponds kept under observation in Delhi during 1973-74 period, six specimens of Mesocyclops leuckarti (Claus, 1857) were found to harbour juvenile stages of Acanthosentis dattai Podder, 1938, parasite of the freshwater fish of the genus Barbus. This is the first record of members of Cyclopidae as intermediate hosts of Acanthocephala in India. The morphology of hitherto unknown juvenile stage of A. dattai is described in this note.", "contents": "First record of a cyclopoid host-Mesocyclops leuckarti (Claus) for an acanthocephalous worm-Acanthosentis dattai Podder from Delhi (India). Among seven species of Cyclops encountered in four water ponds kept under observation in Delhi during 1973-74 period, six specimens of Mesocyclops leuckarti (Claus, 1857) were found to harbour juvenile stages of Acanthosentis dattai Podder, 1938, parasite of the freshwater fish of the genus Barbus. This is the first record of members of Cyclopidae as intermediate hosts of Acanthocephala in India. The morphology of hitherto unknown juvenile stage of A. dattai is described in this note."} {"id": "PMID:1278822", "title": "Rhabdochona minima sp. n. (Nematoda: Spiruroidea) from the loach, Noemacheilus inglisi (Hora), of Nepal.", "content": "A new nematode species, Rhabdochona minima sp.n., is described from the intestine of Noemacheilus inglisi (HORA) OF Nepal (River Ganges drainage system). Characteristics features of this species (only males were found) are the small size of body, size and type of spicules, shape of tail and arrangement of caudal papillae. On the basis of its morphology, R. minima sp.n. belongs to the subgenus Globochona sensu Moravec, 1975. The species Rhabdochona cavasius Rehana et Bilqees, 1973 is considered to be a synonym of R. mazedi Prassad et Sahay, 1965.", "contents": "Rhabdochona minima sp. n. (Nematoda: Spiruroidea) from the loach, Noemacheilus inglisi (Hora), of Nepal. A new nematode species, Rhabdochona minima sp.n., is described from the intestine of Noemacheilus inglisi (HORA) OF Nepal (River Ganges drainage system). Characteristics features of this species (only males were found) are the small size of body, size and type of spicules, shape of tail and arrangement of caudal papillae. On the basis of its morphology, R. minima sp.n. belongs to the subgenus Globochona sensu Moravec, 1975. The species Rhabdochona cavasius Rehana et Bilqees, 1973 is considered to be a synonym of R. mazedi Prassad et Sahay, 1965."} {"id": "PMID:1278838", "title": "The measurement of blood glucose and the definition of hypoglycemia.", "content": "Hypoglycemia is a chemical definition and must be distinguished from neuroglycopenia which is a clinical one. Accurate measurement of blood glucose is possible but many methods still in use may yield incorrect and sometimes dangerously misleading results. Various definitions of hypoglycemia are discussed in relation to methodology and technique of blood glucose measurement. The distinction between fasting and reactive hypoglycemia is emphasized.", "contents": "The measurement of blood glucose and the definition of hypoglycemia. Hypoglycemia is a chemical definition and must be distinguished from neuroglycopenia which is a clinical one. Accurate measurement of blood glucose is possible but many methods still in use may yield incorrect and sometimes dangerously misleading results. Various definitions of hypoglycemia are discussed in relation to methodology and technique of blood glucose measurement. The distinction between fasting and reactive hypoglycemia is emphasized."} {"id": "PMID:1278839", "title": "Hormonal counterregulation in ethanol-induced hypoglycemia-Glucagon and cortisol secretion in pigs.", "content": "Plasma glucagon and cortisol levels were determined in pigs during ethanol-induced hypoglycemia. This hypoglycemia is due to an inhibition of gluconeogenesis which could be related to an abnormal secretion of gluconeogenetic hormones. In six pigs the infusion of ethanol for seven hours (6 mg/kg/min) induced a significant decrease of plasma glucose which was associated with a significant increase of plasma glucagon in the portal vein, femoral artery and hepatic vein. Corresponding with the period of maximal hypoglycemia, plasma cortisol in the femoral artery was also significantly increased. On the other hand, plasma insulin levels were consistently reduced during hypoglycemia. In a second group of six pigs ethanol was infused along with a glucose infusion (3 mg/kg/min) in order to obtain a relatively constant glucose concentration. In this group ethanol did not produce any significant modification of plasma glucagon and cortisol. Therefore, glucagon and cortisol hypersecretion is related to hypoglycemia induced by ethanol. Both the increase in plasma glucagon and cortisol and the decrease in plasma insulin could represent a protective mechanism against alcohol-hypoglycemia.", "contents": "Hormonal counterregulation in ethanol-induced hypoglycemia-Glucagon and cortisol secretion in pigs. Plasma glucagon and cortisol levels were determined in pigs during ethanol-induced hypoglycemia. This hypoglycemia is due to an inhibition of gluconeogenesis which could be related to an abnormal secretion of gluconeogenetic hormones. In six pigs the infusion of ethanol for seven hours (6 mg/kg/min) induced a significant decrease of plasma glucose which was associated with a significant increase of plasma glucagon in the portal vein, femoral artery and hepatic vein. Corresponding with the period of maximal hypoglycemia, plasma cortisol in the femoral artery was also significantly increased. On the other hand, plasma insulin levels were consistently reduced during hypoglycemia. In a second group of six pigs ethanol was infused along with a glucose infusion (3 mg/kg/min) in order to obtain a relatively constant glucose concentration. In this group ethanol did not produce any significant modification of plasma glucagon and cortisol. Therefore, glucagon and cortisol hypersecretion is related to hypoglycemia induced by ethanol. Both the increase in plasma glucagon and cortisol and the decrease in plasma insulin could represent a protective mechanism against alcohol-hypoglycemia."} {"id": "PMID:1278840", "title": "Hypoglycemia--real and imaginary.", "content": "Hypoglycemia, and especially esential reactive hypoglycemia, is overdiagnosed in some parts of the world possible because of misplaced zeal on the part of certain clinicians or misinterpretation of laboratory data relating to the prolonged oral glucose test. This hypoglycemia quackerly has given rise to much concern amongst medical scientists, some of whom have felt it necessary to issue a public warning about the danger of misusing the diagnostic label of hypoglycemia.", "contents": "Hypoglycemia--real and imaginary. Hypoglycemia, and especially esential reactive hypoglycemia, is overdiagnosed in some parts of the world possible because of misplaced zeal on the part of certain clinicians or misinterpretation of laboratory data relating to the prolonged oral glucose test. This hypoglycemia quackerly has given rise to much concern amongst medical scientists, some of whom have felt it necessary to issue a public warning about the danger of misusing the diagnostic label of hypoglycemia."} {"id": "PMID:1278841", "title": "Studies on the hyperglycemic effect of diphenylhydantoin in normal golden hamsters.", "content": "Injected intraperitoneally at a dose of 100 mg/kg body weight into normal hamsters, diphenylhydantoin (DPH) induces a marked increase in blood glucose accompanied by a significant decrease in plasma insulin and a significant increase in plasma glucagon. After administration of phentolamine (5 mg/kg), the hyperglycemic effects of DPH is markedly reduced but remains statistically significant, plasma insulin levels are unchanged and the DPH-induced rise in plasma glucagon is significantly inhibited. Propranolol pretreatment (5 mg/kg) does not affect the DPH-induced changes in blood glucose, plasma insulin and plasma glucagon. Previous administration of reserpine (5 mg/kg/day for two days) does not modify the hyperglycemic response to DPH. These data suggest that the hyperglycemic action of DPH results from both a direct inhibitory effect of this compound on insulin secretion by the beta-cells and a direct stimulatory effect on glucagon secretion by the alpha-cells.", "contents": "Studies on the hyperglycemic effect of diphenylhydantoin in normal golden hamsters. Injected intraperitoneally at a dose of 100 mg/kg body weight into normal hamsters, diphenylhydantoin (DPH) induces a marked increase in blood glucose accompanied by a significant decrease in plasma insulin and a significant increase in plasma glucagon. After administration of phentolamine (5 mg/kg), the hyperglycemic effects of DPH is markedly reduced but remains statistically significant, plasma insulin levels are unchanged and the DPH-induced rise in plasma glucagon is significantly inhibited. Propranolol pretreatment (5 mg/kg) does not affect the DPH-induced changes in blood glucose, plasma insulin and plasma glucagon. Previous administration of reserpine (5 mg/kg/day for two days) does not modify the hyperglycemic response to DPH. These data suggest that the hyperglycemic action of DPH results from both a direct inhibitory effect of this compound on insulin secretion by the beta-cells and a direct stimulatory effect on glucagon secretion by the alpha-cells."} {"id": "PMID:1278842", "title": "The role of enteric hormones in glucose homeostasis.", "content": "A brief review is given of the large numbers of hormones in the pancreas and gut. The concept of the 'entero-insular' axis is discussed and a critical appraisal is given of the claims for various proposed insulinotropic gut hormones. Gastric-inhibitory polypeptide appears at the present time to occupy a leading role in the entero-insular axis. Glucagon-like substances and vasoactive intestinal peptide are of importance in glucose homeostasis by having direct effects on carbohydrate metabolism. The study of the release of gut hormones after food ingestion would indicate that pancreatic glucagon exerts control on glucose hemeostasis during food ingestion, whereas gastric-inhibitory polypeptide may regulate insulin secretion after eating.", "contents": "The role of enteric hormones in glucose homeostasis. A brief review is given of the large numbers of hormones in the pancreas and gut. The concept of the 'entero-insular' axis is discussed and a critical appraisal is given of the claims for various proposed insulinotropic gut hormones. Gastric-inhibitory polypeptide appears at the present time to occupy a leading role in the entero-insular axis. Glucagon-like substances and vasoactive intestinal peptide are of importance in glucose homeostasis by having direct effects on carbohydrate metabolism. The study of the release of gut hormones after food ingestion would indicate that pancreatic glucagon exerts control on glucose hemeostasis during food ingestion, whereas gastric-inhibitory polypeptide may regulate insulin secretion after eating."} {"id": "PMID:1278843", "title": "Studies on the pathogenesis of reactive hypoglycemia: role of insulin and glucagon.", "content": "Fifty-eight patients with biochemical reactive hypoglycemia (blood glucose 45 mg% or less after a 100 g OGTT) were tested, of whom 11 subjects were obese with normal glucose tolerance, 9 were obese with chemical diabetes, 9 had chemical diabetes without obesity, 6 had undergone gastrectomy, 7 had renal glycosuria and 16 were apparently isolated. An exaggerated insulin response to oral glucose was associated with reactive hypoglycemia in the post-gastrectomy syndrome, in normal-weight patients with chemical diabetes and 44% of the patients with the isolated syndrome. In contrast, plasma-insulin values cannot account for the reactive hypoglycemia observed in obese patients (with or without chemical diabetes), in subjects with renal glycosuira and in 56% of the patients with the isolated syndrome. A study of pancreatic-glucagon secretion in a group of twelve subjects with \"isolated normoinsulinemic reactive hypoglycemia\" failed to demonstrate any significant abnormality in the secretion of this hormone during oral glucose tolerance test or intravenous insulin tolerance test. As suggested by Permutt et al. (1973) biguanide therapy may be useful in the treatment of patients presenting severe and symptomatic reactive hypoglycemia which does not respond to classical dietary management.", "contents": "Studies on the pathogenesis of reactive hypoglycemia: role of insulin and glucagon. Fifty-eight patients with biochemical reactive hypoglycemia (blood glucose 45 mg% or less after a 100 g OGTT) were tested, of whom 11 subjects were obese with normal glucose tolerance, 9 were obese with chemical diabetes, 9 had chemical diabetes without obesity, 6 had undergone gastrectomy, 7 had renal glycosuria and 16 were apparently isolated. An exaggerated insulin response to oral glucose was associated with reactive hypoglycemia in the post-gastrectomy syndrome, in normal-weight patients with chemical diabetes and 44% of the patients with the isolated syndrome. In contrast, plasma-insulin values cannot account for the reactive hypoglycemia observed in obese patients (with or without chemical diabetes), in subjects with renal glycosuira and in 56% of the patients with the isolated syndrome. A study of pancreatic-glucagon secretion in a group of twelve subjects with \"isolated normoinsulinemic reactive hypoglycemia\" failed to demonstrate any significant abnormality in the secretion of this hormone during oral glucose tolerance test or intravenous insulin tolerance test. As suggested by Permutt et al. (1973) biguanide therapy may be useful in the treatment of patients presenting severe and symptomatic reactive hypoglycemia which does not respond to classical dietary management."} {"id": "PMID:1278844", "title": "Alcohol hypoglycemia: hormonal changes.", "content": "Changes in hormonal (insulin, glucagon, cortisol and growth hormone), glucose and FFA levels in blood were studied in four young, normal subjects during, and following, alcohol infusion after 12 hours' fasting. Similar studies were made during and after saline infusions in the same subjects after a comparable period of fasting. At the end of the infusions of alcohol or saline an arginine test was performed in order to compare insular and pituitary responses. The same investigations were performed in another three young, healthy subjects after 36 hours' fasting. A chronic alcoholic suffering from hypoglycemia was studied after a 12 hours' fast when he was first seen and again nine months after alcohol withdrawal. The results are in keeping with the hypothesis that alcohol has a priming effect on islet alpha and beta cells when there is no substrate defect. When glycogen stores are exhausted hypoglycemia ensues. An adrenergic reaction supervenes and consequently FFA, cortisol and glucagon rise to high levels. The growth-hormone response to an arginine stimulus was lower after alcohol than after saline in all subjects. In the chronic alcoholic patient the plasma growth-hormone response was initially very poor to all of the stimuli, but after nine months' alcohol withdrawal pituitary activity had returned to normal.", "contents": "Alcohol hypoglycemia: hormonal changes. Changes in hormonal (insulin, glucagon, cortisol and growth hormone), glucose and FFA levels in blood were studied in four young, normal subjects during, and following, alcohol infusion after 12 hours' fasting. Similar studies were made during and after saline infusions in the same subjects after a comparable period of fasting. At the end of the infusions of alcohol or saline an arginine test was performed in order to compare insular and pituitary responses. The same investigations were performed in another three young, healthy subjects after 36 hours' fasting. A chronic alcoholic suffering from hypoglycemia was studied after a 12 hours' fast when he was first seen and again nine months after alcohol withdrawal. The results are in keeping with the hypothesis that alcohol has a priming effect on islet alpha and beta cells when there is no substrate defect. When glycogen stores are exhausted hypoglycemia ensues. An adrenergic reaction supervenes and consequently FFA, cortisol and glucagon rise to high levels. The growth-hormone response to an arginine stimulus was lower after alcohol than after saline in all subjects. In the chronic alcoholic patient the plasma growth-hormone response was initially very poor to all of the stimuli, but after nine months' alcohol withdrawal pituitary activity had returned to normal."} {"id": "PMID:1278852", "title": "A day treatment program for severely disturbed young children.", "content": "An Illinois mental health center operates a day treatment program for young children, who have severe emotional disturbances, often accompanied by profound functional retardation of neurological impairment or both. The primary therapists are child-development specialists; most of the treatment is provided in a classroom setting, through small groups. The author reports on a study of 67 young children who had been treated and discharged, including their psychiatric diagnoses and psychological status at intake and discharge, family characteristics, and treatment outcome an average of two years and seven months after discharge. At that time all but four of the children were living at home. Fifty-two of them attended public school, most in regular classes, and the rest were in therapeutic day schools.", "contents": "A day treatment program for severely disturbed young children. An Illinois mental health center operates a day treatment program for young children, who have severe emotional disturbances, often accompanied by profound functional retardation of neurological impairment or both. The primary therapists are child-development specialists; most of the treatment is provided in a classroom setting, through small groups. The author reports on a study of 67 young children who had been treated and discharged, including their psychiatric diagnoses and psychological status at intake and discharge, family characteristics, and treatment outcome an average of two years and seven months after discharge. At that time all but four of the children were living at home. Fifty-two of them attended public school, most in regular classes, and the rest were in therapeutic day schools."} {"id": "PMID:1278853", "title": "Irrational determinants of the place of psychiatric treatment.", "content": "Observations of 392 women admitted to a psychiatric hospital indicated that 24 were well suited to treatment in a day center and that 208 could feasibly be treated there. However, only 59, or 28 per cent of those for whom day care was feasible, were able to take advantage of that alternative. The others were excluded by financial limitations, refusal to accept the day center option, administrative delays, and inaccurate classification of treatment setting. The authors believe that underuse of the day center was due as much to doctors' inexperience, personal biases, and unfamiliarity with the facilities as it was to psychopathology and financial realities. They found that many clinicians were not aware of the factors that affect their decisions about the use of a partial hospitalization setting.", "contents": "Irrational determinants of the place of psychiatric treatment. Observations of 392 women admitted to a psychiatric hospital indicated that 24 were well suited to treatment in a day center and that 208 could feasibly be treated there. However, only 59, or 28 per cent of those for whom day care was feasible, were able to take advantage of that alternative. The others were excluded by financial limitations, refusal to accept the day center option, administrative delays, and inaccurate classification of treatment setting. The authors believe that underuse of the day center was due as much to doctors' inexperience, personal biases, and unfamiliarity with the facilities as it was to psychopathology and financial realities. They found that many clinicians were not aware of the factors that affect their decisions about the use of a partial hospitalization setting."} {"id": "PMID:1278854", "title": "Family coping with the mentally ill: an unanticipated problem of deinstitutionalization.", "content": "The author studied 125 families to determine the effect of the current movement toward returning mental patients to their homes. From interviews with and attitudinal tests of those families, he reports that they will generally care for the former patient in their home, often with little shame or embarrassment, and usually without rehospitalizing him. But the former patient's presence, especially when severe psychotic symptoms persist, often puts heavy emotional and social strains on the families. He warns that although families accept the physical presence of the patients, the accompanying social rejection could have serious consequences for the community mental health movement.", "contents": "Family coping with the mentally ill: an unanticipated problem of deinstitutionalization. The author studied 125 families to determine the effect of the current movement toward returning mental patients to their homes. From interviews with and attitudinal tests of those families, he reports that they will generally care for the former patient in their home, often with little shame or embarrassment, and usually without rehospitalizing him. But the former patient's presence, especially when severe psychotic symptoms persist, often puts heavy emotional and social strains on the families. He warns that although families accept the physical presence of the patients, the accompanying social rejection could have serious consequences for the community mental health movement."} {"id": "PMID:1278856", "title": "Community families: an alternative to psychiatric hospital intensive care.", "content": "For the past four years Southwest Denver Community Mental Health Services, Inc., has had a system of alternative families who take one or two psychiatric patients who need intensive treatment into their homes; the clients' average stay is ten days. Thus far approximately 220 client placements have been effectively carried out in a network of five homes. Clients who receive psychotropic medication have its effects monitored by a staff psychiatrist, medical nurse coordinator, and nurse clinician. A study conducted by independent researchers over the initial two-year period indicates that the homes are more effective in certain respects than a psychiatric hospital in providing intensive care.", "contents": "Community families: an alternative to psychiatric hospital intensive care. For the past four years Southwest Denver Community Mental Health Services, Inc., has had a system of alternative families who take one or two psychiatric patients who need intensive treatment into their homes; the clients' average stay is ten days. Thus far approximately 220 client placements have been effectively carried out in a network of five homes. Clients who receive psychotropic medication have its effects monitored by a staff psychiatrist, medical nurse coordinator, and nurse clinician. A study conducted by independent researchers over the initial two-year period indicates that the homes are more effective in certain respects than a psychiatric hospital in providing intensive care."} {"id": "PMID:1278873", "title": "Computerized system analyzes epidemiological data.", "content": "The computer is a valuable tool in helping to analyze epidemiological data that are collected through the infection surveillance system. The computerized system described has many significant advantages over the manual system of infection surveillance: quick assimilation, computation, and dissemination of the nosocomial infection summary report (within seven working days of the month's end); identification of infection problems and problem areas; and ability to retrieve data necessary for a complete establishment of a hypothesis regarding cause and effect implicated by an epidemiological investigation. Above all, timely and accurate infection data must be obtained in order for the reports to be beneficial in the decision-making process used by the infection control committee. Manual systems of month-to-month correlation of infection data are difficult and extremely time consuming for the surveillance person. Often the infection control committee cannot act intelligently and quickly because it is not knowledgeable of current trends occurring within the hospital. The computer has a number of limitations, and any computerized surveillance system should be approached with caution, especially during the developmental stages. The computer uses input data, follows instructions, and thus formulates output. If the computer is given either inadequate input data or inaccurately programmed instructions, the output will be erroneous. Therefore, a close working relationship should be established between the epidemiologist and the hospital's data processing department. The goals of the system must be clearly defined and understood by both areas. Once the system is established, the output is only as good as the data supplied by the epidemiologist. If this system is properly utilized, valuable information can be obtained that would have been difficult to obtain using a manual surveillance method.", "contents": "Computerized system analyzes epidemiological data. The computer is a valuable tool in helping to analyze epidemiological data that are collected through the infection surveillance system. The computerized system described has many significant advantages over the manual system of infection surveillance: quick assimilation, computation, and dissemination of the nosocomial infection summary report (within seven working days of the month's end); identification of infection problems and problem areas; and ability to retrieve data necessary for a complete establishment of a hypothesis regarding cause and effect implicated by an epidemiological investigation. Above all, timely and accurate infection data must be obtained in order for the reports to be beneficial in the decision-making process used by the infection control committee. Manual systems of month-to-month correlation of infection data are difficult and extremely time consuming for the surveillance person. Often the infection control committee cannot act intelligently and quickly because it is not knowledgeable of current trends occurring within the hospital. The computer has a number of limitations, and any computerized surveillance system should be approached with caution, especially during the developmental stages. The computer uses input data, follows instructions, and thus formulates output. If the computer is given either inadequate input data or inaccurately programmed instructions, the output will be erroneous. Therefore, a close working relationship should be established between the epidemiologist and the hospital's data processing department. The goals of the system must be clearly defined and understood by both areas. Once the system is established, the output is only as good as the data supplied by the epidemiologist. If this system is properly utilized, valuable information can be obtained that would have been difficult to obtain using a manual surveillance method."} {"id": "PMID:1278895", "title": "A review of prescription pricing and a call for equitable payment.", "content": "All of these systems are designed in order than a fair and equitable profit may be included for pharmaceutical services but this profit need not be excessive. For many years, the pharmacy has been considered a profit generator to offset the losses in other services departments. However, because of increased consumer awareness of prices and the close scrutiny of third party payers, including the federal government, this practice appears to be diminishing. With enactment of a comprehensive national health insurance, it is unlikely that the government will allow the type of cost accounting whereby one department generates profit to offset a deficit in other departments. Therefore, hospitals must develop a fair, equitable, and efficient pricing system. It is believed that the per diem charge system may be the most suitable for several reasons. First, it provides a mechanism for the charging of services not associated with the dispensing of pharmaceuticals. Second, this system appears to be more efficient because it eliminates the need to price individual prescriptions, which may result in an annual savings of $20 per bed as reported in one study. Third, the per diem mechanism promotes cost efficiency by focusing attention on the actual daily operating cost of providing pharmaceutical services. It is obvious that the general public is aware of the expense of health care, including pharmaceuticals. Hospital pharmacy has enjoyed a relative period of immunity from such public scrutiny for many years. We must, therefore, make every effort to encourage a pricing system that is equitable to both the hospital and the patient. In viewing these four mechanisms of payment, it is believed that the per diem rate for pharmaceutical services can and will be utilized to a much greater extent. When one considers its advantages along with the imminence of some form of a national health insurance program, this system appears to be the reimbursement mechanism of the future.", "contents": "A review of prescription pricing and a call for equitable payment. All of these systems are designed in order than a fair and equitable profit may be included for pharmaceutical services but this profit need not be excessive. For many years, the pharmacy has been considered a profit generator to offset the losses in other services departments. However, because of increased consumer awareness of prices and the close scrutiny of third party payers, including the federal government, this practice appears to be diminishing. With enactment of a comprehensive national health insurance, it is unlikely that the government will allow the type of cost accounting whereby one department generates profit to offset a deficit in other departments. Therefore, hospitals must develop a fair, equitable, and efficient pricing system. It is believed that the per diem charge system may be the most suitable for several reasons. First, it provides a mechanism for the charging of services not associated with the dispensing of pharmaceuticals. Second, this system appears to be more efficient because it eliminates the need to price individual prescriptions, which may result in an annual savings of $20 per bed as reported in one study. Third, the per diem mechanism promotes cost efficiency by focusing attention on the actual daily operating cost of providing pharmaceutical services. It is obvious that the general public is aware of the expense of health care, including pharmaceuticals. Hospital pharmacy has enjoyed a relative period of immunity from such public scrutiny for many years. We must, therefore, make every effort to encourage a pricing system that is equitable to both the hospital and the patient. In viewing these four mechanisms of payment, it is believed that the per diem rate for pharmaceutical services can and will be utilized to a much greater extent. When one considers its advantages along with the imminence of some form of a national health insurance program, this system appears to be the reimbursement mechanism of the future."} {"id": "PMID:1278933", "title": "Effects of active and passive immunization on Mycoplasma pulmonis-induced pneumonia in mice.", "content": "Parenteral immunization of C3H mice with viable Mycoplasma pulmonis organisms protected them from pneumonia induced by intranasal inoculation of these organisms. Spleen cells obtained from immunized mice were ineffective in preventing syngeneic recipients from developint respiratory disease. In contrast, convalescent-phase serum enhanced the clearance of mycoplasmas from the respiratory tract of mice challenged with a small number of organisms. Further, although 'immune' serum had no detectable effect on the number of mycoplasmas in the respiratory tract of mice challenged with a large number of organisms, such animals did not develop pneumonia. Since the pneumonia appears to be the results of the host's immune response to the mycoplasma, it is suggested that the transferred 'immune' serum may act by suppressing the immune response so that mice develop less severe lung lesions. This suggestion is supported by the observation that the complement-fixing antibody response of passively immunized mice was suppressed.", "contents": "Effects of active and passive immunization on Mycoplasma pulmonis-induced pneumonia in mice. Parenteral immunization of C3H mice with viable Mycoplasma pulmonis organisms protected them from pneumonia induced by intranasal inoculation of these organisms. Spleen cells obtained from immunized mice were ineffective in preventing syngeneic recipients from developint respiratory disease. In contrast, convalescent-phase serum enhanced the clearance of mycoplasmas from the respiratory tract of mice challenged with a small number of organisms. Further, although 'immune' serum had no detectable effect on the number of mycoplasmas in the respiratory tract of mice challenged with a large number of organisms, such animals did not develop pneumonia. Since the pneumonia appears to be the results of the host's immune response to the mycoplasma, it is suggested that the transferred 'immune' serum may act by suppressing the immune response so that mice develop less severe lung lesions. This suggestion is supported by the observation that the complement-fixing antibody response of passively immunized mice was suppressed."} {"id": "PMID:1278934", "title": "The effect of Leishmania tropica on stimulation of lymphocytes with phytohaemagglutinin.", "content": "Cell-mediated immune (CMI) responses are important in the immunity against leishmanial infections. However, infection persists in the presence of CMI for unknown reasons. Evidence is presented that L. tropica and its products are capable of inhibition of the stimulation of lymphocytes by PHA. This inhibition is dose dependent, and not dependent on competition for nutrients in the medium, nor on neutralization of PHA. The inhibition is observed on the lymphocytes of species susceptible to leishmanial infection, and not operative in resistant species. The mechanisms of the lymphocyte suppression are discussed.", "contents": "The effect of Leishmania tropica on stimulation of lymphocytes with phytohaemagglutinin. Cell-mediated immune (CMI) responses are important in the immunity against leishmanial infections. However, infection persists in the presence of CMI for unknown reasons. Evidence is presented that L. tropica and its products are capable of inhibition of the stimulation of lymphocytes by PHA. This inhibition is dose dependent, and not dependent on competition for nutrients in the medium, nor on neutralization of PHA. The inhibition is observed on the lymphocytes of species susceptible to leishmanial infection, and not operative in resistant species. The mechanisms of the lymphocyte suppression are discussed."} {"id": "PMID:1278935", "title": "Decline of passively acquired antibodies in young and adult rats.", "content": "The rate of decline (half-life) of passively acquired antibodies was studied in young and adult rats. There was a wide variation in half-life when varying concentrations of diphtheria or tetanus antibody were administered by intraperitoneal injection; half-lives ranged from 1-2 to 12-0 days in both age groups. When different concentrations of diphtheria and tetanus antibody were administered together by the same route, significant differences in half-lives were demonstrated in individuals of each group. Each of the curves describing the relationship between initial antibody titre and half-life took the shape of a rectangular hyperbola; individuals with high initial titres had short half-lifes, whereas in animals with low initial titres antibody declined at a slower rate. The results are in agreement with those previously reported for the decline of maternally acquired antibodies in infants and young rats and for the catabolism of IgG.", "contents": "Decline of passively acquired antibodies in young and adult rats. The rate of decline (half-life) of passively acquired antibodies was studied in young and adult rats. There was a wide variation in half-life when varying concentrations of diphtheria or tetanus antibody were administered by intraperitoneal injection; half-lives ranged from 1-2 to 12-0 days in both age groups. When different concentrations of diphtheria and tetanus antibody were administered together by the same route, significant differences in half-lives were demonstrated in individuals of each group. Each of the curves describing the relationship between initial antibody titre and half-life took the shape of a rectangular hyperbola; individuals with high initial titres had short half-lifes, whereas in animals with low initial titres antibody declined at a slower rate. The results are in agreement with those previously reported for the decline of maternally acquired antibodies in infants and young rats and for the catabolism of IgG."} {"id": "PMID:1278983", "title": "Experience with the dynamic compression plate (DCP) in 418 recent fractures of the tibial shaft.", "content": "A consecutive series of 435 fresh fractures of the tibial shaft was internally fixed by the new dynamic compression plate (ASIF-DCP). All but 2 cases could be reviewed personally within 1-2 years after operation, while 15 patients had died. The functional results and postoperative complications are reported separately for the 334 closed and 101 open fractures. In spite of a higher rate of complication in the open fractures, their functional results were about as good as in the closed cases. In our experience the new dynamic compression plate proved to be very satisfactory for internal fixation of fractures of the tibia.", "contents": "Experience with the dynamic compression plate (DCP) in 418 recent fractures of the tibial shaft. A consecutive series of 435 fresh fractures of the tibial shaft was internally fixed by the new dynamic compression plate (ASIF-DCP). All but 2 cases could be reviewed personally within 1-2 years after operation, while 15 patients had died. The functional results and postoperative complications are reported separately for the 334 closed and 101 open fractures. In spite of a higher rate of complication in the open fractures, their functional results were about as good as in the closed cases. In our experience the new dynamic compression plate proved to be very satisfactory for internal fixation of fractures of the tibia."} {"id": "PMID:1278984", "title": "Lactic dehydrogenase isoenzymes following head injury.", "content": "Serial levels of lactic dehydrogenase (LDH) isoenzymes have been measured in 92 neurosurgical patients with damaged brains, including 77 suffering from head injury. Serum LDH isoenzymes 1 and 2 rise in the injured group and generally reflect the degree of parenchymal brain damage. The method has possible diagnostic applications, as well as some prognostic use.", "contents": "Lactic dehydrogenase isoenzymes following head injury. Serial levels of lactic dehydrogenase (LDH) isoenzymes have been measured in 92 neurosurgical patients with damaged brains, including 77 suffering from head injury. Serum LDH isoenzymes 1 and 2 rise in the injured group and generally reflect the degree of parenchymal brain damage. The method has possible diagnostic applications, as well as some prognostic use."} {"id": "PMID:1278985", "title": "The importance of the ulnar side of the wrist in fractures of the distal end of the radius.", "content": "In a series of 81 fractures of the distal end of the radius, 20% had unsatisfactory results. Damage to the ulnar collateral mechanism adversely affects the clinical result despite a good anatomical result. Immobilization of injuries to the ulnar collateral mechanism should be in pronation and ulnar deviation even when there is no significant radial displacement.", "contents": "The importance of the ulnar side of the wrist in fractures of the distal end of the radius. In a series of 81 fractures of the distal end of the radius, 20% had unsatisfactory results. Damage to the ulnar collateral mechanism adversely affects the clinical result despite a good anatomical result. Immobilization of injuries to the ulnar collateral mechanism should be in pronation and ulnar deviation even when there is no significant radial displacement."} {"id": "PMID:1278986", "title": "Treatment of fracture-dislocation of the hip with complete destruction of the proximal end of femur by total hip arthroplasty.", "content": "A case of fracture-dislocation of the hip with loss of bone from the proximal part of the femur due to a war injury is described. It is concluded that a total hip arthroplasty after 3 months is a suitable treatment.", "contents": "Treatment of fracture-dislocation of the hip with complete destruction of the proximal end of femur by total hip arthroplasty. A case of fracture-dislocation of the hip with loss of bone from the proximal part of the femur due to a war injury is described. It is concluded that a total hip arthroplasty after 3 months is a suitable treatment."} {"id": "PMID:1278987", "title": "The risk of deep-vein thrombosis after operations on a bloodless lower limb. A venographic study.", "content": "In 17% of 40 patients undergoing operation in a bloodless field on the lower limb, thrombosis was diagnosed phlebographically. Phlebography was performed between the second and eighth postoperative day. The incidence of thrombosis in this series was relatively low, considering other reports on postoperative thrombosis and the theoretical dangers of thrombosis involved in the use of a tourniquet. Factors which could explain the relatively low frequency of postoperative thrombosis are discussed.", "contents": "The risk of deep-vein thrombosis after operations on a bloodless lower limb. A venographic study. In 17% of 40 patients undergoing operation in a bloodless field on the lower limb, thrombosis was diagnosed phlebographically. Phlebography was performed between the second and eighth postoperative day. The incidence of thrombosis in this series was relatively low, considering other reports on postoperative thrombosis and the theoretical dangers of thrombosis involved in the use of a tourniquet. Factors which could explain the relatively low frequency of postoperative thrombosis are discussed."} {"id": "PMID:1278988", "title": "Non-union in fractures of the humeral shaft.", "content": "Twenty-nine patients with non-union of the humeral shaft, who were treated in 3 major Vancouver hospitals, were studied. Reasons for non-union, effectiveness of various treatment methods, and complications are discussed. Fractures occurring in the middle third of the humeral shaft, comminuted or open fractures and those treated early by open reduction, are more prone to non-union. Nearly 50% of the patients with non-union were chronic alcoholics. Compression plating with cancellous bone grafting gave the best rate of healing. However, both early and late operative treatment gave a relatively high complication rate.", "contents": "Non-union in fractures of the humeral shaft. Twenty-nine patients with non-union of the humeral shaft, who were treated in 3 major Vancouver hospitals, were studied. Reasons for non-union, effectiveness of various treatment methods, and complications are discussed. Fractures occurring in the middle third of the humeral shaft, comminuted or open fractures and those treated early by open reduction, are more prone to non-union. Nearly 50% of the patients with non-union were chronic alcoholics. Compression plating with cancellous bone grafting gave the best rate of healing. However, both early and late operative treatment gave a relatively high complication rate."} {"id": "PMID:1278989", "title": "Medical planning for disaster in Israel. Evaluation of the military surgical experience in the October 1973 War, and implications for the organization of the civilian disaster services.", "content": "During its 27 years of existence, Israel has experienced four wars and dozens of mass casualty situations from various causes. This experience has led to the development of a plan for the management of mass casualties. This plan was put to the test in the October War of 1973 and proved successful. Although disasters and procedures vary widely in time and location certain principles of organization and management apply to most of them. In this paper the organization of the evacuation and management of the casualties in the October War is evaluated and its implications in the organization of civilian disaster services discussed.", "contents": "Medical planning for disaster in Israel. Evaluation of the military surgical experience in the October 1973 War, and implications for the organization of the civilian disaster services. During its 27 years of existence, Israel has experienced four wars and dozens of mass casualty situations from various causes. This experience has led to the development of a plan for the management of mass casualties. This plan was put to the test in the October War of 1973 and proved successful. Although disasters and procedures vary widely in time and location certain principles of organization and management apply to most of them. In this paper the organization of the evacuation and management of the casualties in the October War is evaluated and its implications in the organization of civilian disaster services discussed."} {"id": "PMID:1278991", "title": "Hang gliding injuries. A preliminary report.", "content": "Six cases of injury associated with hang gliding are reported. The history and technique of the sport are briefly described. Fractures of the spine and limbs are the commonest injuries encountered in this high risk activity and many of them could be avoided or reduced in severity by simple safety precautions.", "contents": "Hang gliding injuries. A preliminary report. Six cases of injury associated with hang gliding are reported. The history and technique of the sport are briefly described. Fractures of the spine and limbs are the commonest injuries encountered in this high risk activity and many of them could be avoided or reduced in severity by simple safety precautions."} {"id": "PMID:1278992", "title": "Hepatic trauma involving the hepatic veins and vena cava.", "content": "The control of massive haemorrhage in major hepatic injury with caval damage is extremely difficult. Our experience with 5 such patients is reported. The management and operative techniques involved are discussed. In 3 patients control was obtained and repair effected without recourse to internal caval shunting. One of these patients survived in spite of extensive injuries.", "contents": "Hepatic trauma involving the hepatic veins and vena cava. The control of massive haemorrhage in major hepatic injury with caval damage is extremely difficult. Our experience with 5 such patients is reported. The management and operative techniques involved are discussed. In 3 patients control was obtained and repair effected without recourse to internal caval shunting. One of these patients survived in spite of extensive injuries."} {"id": "PMID:1278994", "title": "An unusual seat-belt injury in a doctor.", "content": "The personal experience of a general practitioner who sustained a fracture-dislocation of the atlanto-axial joint is recorded. The inefficient application of an unyielding (non-inertial) lap and diagonal seat belt permitted this injury, although one does not know what other injuries might have occurred had the belt not been worn.", "contents": "An unusual seat-belt injury in a doctor. The personal experience of a general practitioner who sustained a fracture-dislocation of the atlanto-axial joint is recorded. The inefficient application of an unyielding (non-inertial) lap and diagonal seat belt permitted this injury, although one does not know what other injuries might have occurred had the belt not been worn."} {"id": "PMID:1278995", "title": "Interactions of antisera, sera, and oral fluid with glucosyltransferases.", "content": "Partially purified glucosyltransferases (GTF) isolated from Streptococcus mutans OMZ 176 and respective rabbit antisera were used to study enzyme-antibody interactions. A comparison between sensitive serological techniques and a functional inhibition test based on a radioenzyme assay demonstrated that the latter test system was the only one that discriminated between different antisera. Positive reactions in high dilutions in the former test systems were explained by the involvement of non-GTF contaminants and/or antibodies against enzyme regions distant to the catalytic site. The minute cross-reactions between two enzyme fractions and the respective antisera in the functional inhibition test indicated that the two immunogens contained mainly GTF that differed in the structure of their catalytic region. Control rabbit sera, rat oral fluid, and insoluble and soluble glucans considerably activated the GTF eluted with a 0.5 M phosphate buffer from hydroxapatite. It is suggested that these enzymes had additional binding sites for macromolecules inherent to rabbit sera and rat oral fluid, respectively, and that the observed increase in enzyme activity was due to a more stable enzyme conformation. Possibly the stimulation of GTF by the soluble glucan fraction was caused by a primer and/or acceptor function; however, this was not the case of the insoluble glucan. A stable complex was formed in the absence of the enzyme substrate, sucrose, the activity of which was not readily enhanced. It is concluded that the GTF of strain OMZ 176 are composed of multiple, multi-reactive molecules that enable these enzymes to act as cross-linking agents.", "contents": "Interactions of antisera, sera, and oral fluid with glucosyltransferases. Partially purified glucosyltransferases (GTF) isolated from Streptococcus mutans OMZ 176 and respective rabbit antisera were used to study enzyme-antibody interactions. A comparison between sensitive serological techniques and a functional inhibition test based on a radioenzyme assay demonstrated that the latter test system was the only one that discriminated between different antisera. Positive reactions in high dilutions in the former test systems were explained by the involvement of non-GTF contaminants and/or antibodies against enzyme regions distant to the catalytic site. The minute cross-reactions between two enzyme fractions and the respective antisera in the functional inhibition test indicated that the two immunogens contained mainly GTF that differed in the structure of their catalytic region. Control rabbit sera, rat oral fluid, and insoluble and soluble glucans considerably activated the GTF eluted with a 0.5 M phosphate buffer from hydroxapatite. It is suggested that these enzymes had additional binding sites for macromolecules inherent to rabbit sera and rat oral fluid, respectively, and that the observed increase in enzyme activity was due to a more stable enzyme conformation. Possibly the stimulation of GTF by the soluble glucan fraction was caused by a primer and/or acceptor function; however, this was not the case of the insoluble glucan. A stable complex was formed in the absence of the enzyme substrate, sucrose, the activity of which was not readily enhanced. It is concluded that the GTF of strain OMZ 176 are composed of multiple, multi-reactive molecules that enable these enzymes to act as cross-linking agents."} {"id": "PMID:1278996", "title": "Production of highly cross-reactive hemagglutination-inhibiting influenza antibodies in ferrets.", "content": "Ferrets were sequentially infected at time intervals of 3 weeks with different influenza virus A strains. It was found that secondary infection can result in the appearance of antibodies highly cross-reacting with a virus strain closely related to the strain of first infection. Such highly cross-reacting antibodies were designated as HCR antibodies. Evidence is presented that HCR antibodies were not antineuraminidase antibodies and, in addition, were not specifically oriented to the strain with which the crossing was observed. When using time intervals of 3 weeks between infections, no increase after secondary infection of antibodies oriented to the strain of first infection was recorded. However, when time intervals of 4 to 5 months between infections were used, secondary infections resulted in an increase of antibodies oriented to the strain of first infection (\"original antigenic sin\") but not in the appearance of HCR antibodies. In addition, antibodies combining specifically with both infecting strains, designated as doubly specific antibodies, were found. Thus, the conclusion was reached that the original antigenic sin phenomenon and the appearance of HCR antibodies are mutually exclusive events.", "contents": "Production of highly cross-reactive hemagglutination-inhibiting influenza antibodies in ferrets. Ferrets were sequentially infected at time intervals of 3 weeks with different influenza virus A strains. It was found that secondary infection can result in the appearance of antibodies highly cross-reacting with a virus strain closely related to the strain of first infection. Such highly cross-reacting antibodies were designated as HCR antibodies. Evidence is presented that HCR antibodies were not antineuraminidase antibodies and, in addition, were not specifically oriented to the strain with which the crossing was observed. When using time intervals of 3 weeks between infections, no increase after secondary infection of antibodies oriented to the strain of first infection was recorded. However, when time intervals of 4 to 5 months between infections were used, secondary infections resulted in an increase of antibodies oriented to the strain of first infection (\"original antigenic sin\") but not in the appearance of HCR antibodies. In addition, antibodies combining specifically with both infecting strains, designated as doubly specific antibodies, were found. Thus, the conclusion was reached that the original antigenic sin phenomenon and the appearance of HCR antibodies are mutually exclusive events."} {"id": "PMID:1278997", "title": "Purification of complement-fixing antigens of Rickettsia sennetsu by ether treatment.", "content": "Soluble and particulate complement-fixing antigens of Rickettsia sennetsu were prepared from spleen suspensions of mice infected with the rickettsia and treated with cyclophosphamide. The medium used during purification of antigens, a solution consisting of equal volumes of phosphate-glutamate-sucrose buffer and veronal-buffered saline, was suitable for obtaining antigens with high titers and no anti-complementary activity. By heat treatment, it was demonstrated that the soluble antigen was heat labile and the particulate antigen was heat stable. The soluble antigen was precipitated by 80% saturation with ammonium sulfate. Cross-complement fixation tests using both soluble and particulate antigens revealed that there was no antigenic difference among strains of R. Sennetsu. On the other hand, no cross-activity was observed between R. sennetsu and R. orientalis.", "contents": "Purification of complement-fixing antigens of Rickettsia sennetsu by ether treatment. Soluble and particulate complement-fixing antigens of Rickettsia sennetsu were prepared from spleen suspensions of mice infected with the rickettsia and treated with cyclophosphamide. The medium used during purification of antigens, a solution consisting of equal volumes of phosphate-glutamate-sucrose buffer and veronal-buffered saline, was suitable for obtaining antigens with high titers and no anti-complementary activity. By heat treatment, it was demonstrated that the soluble antigen was heat labile and the particulate antigen was heat stable. The soluble antigen was precipitated by 80% saturation with ammonium sulfate. Cross-complement fixation tests using both soluble and particulate antigens revealed that there was no antigenic difference among strains of R. Sennetsu. On the other hand, no cross-activity was observed between R. sennetsu and R. orientalis."} {"id": "PMID:1278998", "title": "Role of Agrobacterium cell envelope lipopolysaccharide in infection site attachment.", "content": "Lipopolysaccharide (LPS) isolated from Agrobacterium tumefaciens inhibited tumor induction by virulent bacteria. LPS from site-binding strains was not effective if added to the plant wound shortly after the bacteria, and LPS from avirulent, non-site-binding strains of Agrobacterium was not inhibitory regardless of the order of addition. However, LPS and whole cells of avirulent strains NT1 and IIBNV6, which lack of Agrobacterim virulence plasmid, were inhibitory. Chromosomal deoxyribonucleic acid thus determines specificity of this essential component of the Agrobacterium infection process.", "contents": "Role of Agrobacterium cell envelope lipopolysaccharide in infection site attachment. Lipopolysaccharide (LPS) isolated from Agrobacterium tumefaciens inhibited tumor induction by virulent bacteria. LPS from site-binding strains was not effective if added to the plant wound shortly after the bacteria, and LPS from avirulent, non-site-binding strains of Agrobacterium was not inhibitory regardless of the order of addition. However, LPS and whole cells of avirulent strains NT1 and IIBNV6, which lack of Agrobacterim virulence plasmid, were inhibitory. Chromosomal deoxyribonucleic acid thus determines specificity of this essential component of the Agrobacterium infection process."} {"id": "PMID:1278999", "title": "Presence and subcellular localization of two distinct mitogenic fractions in the cells of Nocardia rubra and Nocardia opaca: preparation of soluble mitogenic peptidoglycan fractions.", "content": "Fractionation of cells of Nocardia rubra and Nocardia opaca led to the separation of the cell wall and a \"cytoplasmic\" fraction. Both fractions were mitogenic for the splenocytes of AKR and nude mice and of rabbits. The peptidoglycan was the active part of the cell wall fraction. The products solubilized by the action of Streptomyces albus G peptidases on the peptidoglycan of N. rubra were mitogenic, but the products solubilized by lysoyme were not. Tentative structures are proposed for these fractions. The most active part of the cytoplasmic fractions could be sedimented by centrifugation and seemed to be related to the cytoplasmic membrane.", "contents": "Presence and subcellular localization of two distinct mitogenic fractions in the cells of Nocardia rubra and Nocardia opaca: preparation of soluble mitogenic peptidoglycan fractions. Fractionation of cells of Nocardia rubra and Nocardia opaca led to the separation of the cell wall and a \"cytoplasmic\" fraction. Both fractions were mitogenic for the splenocytes of AKR and nude mice and of rabbits. The peptidoglycan was the active part of the cell wall fraction. The products solubilized by the action of Streptomyces albus G peptidases on the peptidoglycan of N. rubra were mitogenic, but the products solubilized by lysoyme were not. Tentative structures are proposed for these fractions. The most active part of the cytoplasmic fractions could be sedimented by centrifugation and seemed to be related to the cytoplasmic membrane."} {"id": "PMID:1279000", "title": "Demonstration of macrophage chemotactic factors in the aqueous humor during experimental immunogenic uveitis in rabbits.", "content": "Factors in the queous humor capable of increasing the random migration and chemotaxis of monocytes were demonstrated during experimental uveitis in the rabbit. Injection of endotoxin-free human serum albumin into the vitreous produced a severe inflammation detectable after 7 days and maximal between 12 to 21 days. Aqueous humor was measured for chemotactic activity with a modified Boyden chamber, which permitted the use of volumes of less than 0.025 ml. Chematactic activity was measurable during the primary inflammation and remained elevated for a short period of time after clinical inflammation and anterior chamber cellular reaction had decreased. A severe reinduction uveitis could be initiated by the intravenous injection of human serum albumin after day 30. Chemotactic factors could be measured at high titers by 8 h after this intravenous challenge.", "contents": "Demonstration of macrophage chemotactic factors in the aqueous humor during experimental immunogenic uveitis in rabbits. Factors in the queous humor capable of increasing the random migration and chemotaxis of monocytes were demonstrated during experimental uveitis in the rabbit. Injection of endotoxin-free human serum albumin into the vitreous produced a severe inflammation detectable after 7 days and maximal between 12 to 21 days. Aqueous humor was measured for chemotactic activity with a modified Boyden chamber, which permitted the use of volumes of less than 0.025 ml. Chematactic activity was measurable during the primary inflammation and remained elevated for a short period of time after clinical inflammation and anterior chamber cellular reaction had decreased. A severe reinduction uveitis could be initiated by the intravenous injection of human serum albumin after day 30. Chemotactic factors could be measured at high titers by 8 h after this intravenous challenge."} {"id": "PMID:1279001", "title": "Complement system in pneumococcal infections.", "content": "The properdin or alternate complement pathway may function as a heat-labile opsonin for pneumococci, and evidence has been sought for its activation in pneumococcal infections. Twenty-two patients had determinations of C1q, C4, properdin factor B, C3, and hemolytic complement during hospitalization for pneumococcal infection. Measurements were made during the first 36 h after admission on 16 patients and later during recovery on 16. The admission and recovery values were compared statistically with each other and with the levels of 15 normal individuals. The admission and recovery mean values were normal and nearly identical for C1q and C4, which are two early components of the classical pathway. The mean level of factor N, a properdin pathway component, was significantly depressed on admission, but the mean recovery value was normal. Admission levels for C3, a component of the late common pathway, were depressed, and recovery values were normal. Total hemolytic complement was decreased on admission, although the decrease was not significant for the patients with both admission and recovery determinations. The findings are consistent with the hypothesis that factor B is turned over rapidly, or consumed, early in pneumococcal infections; alternatively, persons with low baseline factor B levels may be particularly susceptible to pneumococcal infection.", "contents": "Complement system in pneumococcal infections. The properdin or alternate complement pathway may function as a heat-labile opsonin for pneumococci, and evidence has been sought for its activation in pneumococcal infections. Twenty-two patients had determinations of C1q, C4, properdin factor B, C3, and hemolytic complement during hospitalization for pneumococcal infection. Measurements were made during the first 36 h after admission on 16 patients and later during recovery on 16. The admission and recovery values were compared statistically with each other and with the levels of 15 normal individuals. The admission and recovery mean values were normal and nearly identical for C1q and C4, which are two early components of the classical pathway. The mean level of factor N, a properdin pathway component, was significantly depressed on admission, but the mean recovery value was normal. Admission levels for C3, a component of the late common pathway, were depressed, and recovery values were normal. Total hemolytic complement was decreased on admission, although the decrease was not significant for the patients with both admission and recovery determinations. The findings are consistent with the hypothesis that factor B is turned over rapidly, or consumed, early in pneumococcal infections; alternatively, persons with low baseline factor B levels may be particularly susceptible to pneumococcal infection."} {"id": "PMID:1279002", "title": "Relationship of the cell wall composition of group H streptococci and Streptococcus sanguis to their serological properties.", "content": "Previous studies indicated the a antigen was widely distributed among strains of Streptococcus sanguis and the group H streptococci. The cell walls of strains containing this antigen had moderate to large quantities of rhamnose, small amounts of phosphorus, and little to no ribitol. The molar ratios of the peptidoglycan amino acids and hexosamines suggested a di-alanyl cross bridge. The homogeneity of the walls of these strains suggested that serological group H can be considered synonymous with S. sanguis. In contrast those strains that did not contain the a antigen had only small amounts of rhamnose in their cell walls, galactosamine and ribitol were always detected, and large quantitites of phosphorus were present. The molar ratios of peptidoglycan components in the latter strains suggested a direct alanyl-lysl cross bridge. Although many of these strains had been classified either as S. sanguis or group H streptococci because of minor serological cross-reactions and similar biochemical properties, the distinct differences between the composition of their cell walls and those of S. sanguis and group H streptococci indicate that they do not belong in this species or group. The cell walls of strains containing the a antigen are relatively homogeneous and therefore it is suggested that cells containing this antigen be considered Lancefield serological group H.", "contents": "Relationship of the cell wall composition of group H streptococci and Streptococcus sanguis to their serological properties. Previous studies indicated the a antigen was widely distributed among strains of Streptococcus sanguis and the group H streptococci. The cell walls of strains containing this antigen had moderate to large quantities of rhamnose, small amounts of phosphorus, and little to no ribitol. The molar ratios of the peptidoglycan amino acids and hexosamines suggested a di-alanyl cross bridge. The homogeneity of the walls of these strains suggested that serological group H can be considered synonymous with S. sanguis. In contrast those strains that did not contain the a antigen had only small amounts of rhamnose in their cell walls, galactosamine and ribitol were always detected, and large quantitites of phosphorus were present. The molar ratios of peptidoglycan components in the latter strains suggested a direct alanyl-lysl cross bridge. Although many of these strains had been classified either as S. sanguis or group H streptococci because of minor serological cross-reactions and similar biochemical properties, the distinct differences between the composition of their cell walls and those of S. sanguis and group H streptococci indicate that they do not belong in this species or group. The cell walls of strains containing the a antigen are relatively homogeneous and therefore it is suggested that cells containing this antigen be considered Lancefield serological group H."} {"id": "PMID:1279003", "title": "Ontogeny of human cell-mediated immunity: age-related variation of in vitro infantile lymphocyte transformation.", "content": "Thymidine uptake of unstimulated and of phytohemagglutinin (PHA)-, streptokinase-streptodornase (SK-SD)- and candida extract (candida)-stimulated lymphocytes of normal infants less than 20 months old was evaluated. Thymidine uptake of unstimulated and PHA-stimulated young infants' lymphocytes was avid, resembling that of newborn cells. Over periods of weeks to months, infantile lymphocytes demonstrated transition in unstimulated and PHA-induced thymidine uptake from response patterns like cord blood cells to ones more characteristic of adult lymphocytes. Candida- and SK-SD-induced thymidine uptake of lymphocytes from very young infants was likewise apparently quite avid, resembling cord blood cells. However, factoring out high unstimulated thymidine uptake by conversion of data to stimulation indexes clarified differing paces of acquisition of transformation responsiveness of the two naturally acquired infectious antigens. Specific lymphocytes reactivity to SK-SD was quite low in all groups of infants compared with candida-induced transformation, which in some infants acquired adult proportions.", "contents": "Ontogeny of human cell-mediated immunity: age-related variation of in vitro infantile lymphocyte transformation. Thymidine uptake of unstimulated and of phytohemagglutinin (PHA)-, streptokinase-streptodornase (SK-SD)- and candida extract (candida)-stimulated lymphocytes of normal infants less than 20 months old was evaluated. Thymidine uptake of unstimulated and PHA-stimulated young infants' lymphocytes was avid, resembling that of newborn cells. Over periods of weeks to months, infantile lymphocytes demonstrated transition in unstimulated and PHA-induced thymidine uptake from response patterns like cord blood cells to ones more characteristic of adult lymphocytes. Candida- and SK-SD-induced thymidine uptake of lymphocytes from very young infants was likewise apparently quite avid, resembling cord blood cells. However, factoring out high unstimulated thymidine uptake by conversion of data to stimulation indexes clarified differing paces of acquisition of transformation responsiveness of the two naturally acquired infectious antigens. Specific lymphocytes reactivity to SK-SD was quite low in all groups of infants compared with candida-induced transformation, which in some infants acquired adult proportions."} {"id": "PMID:1279004", "title": "Dextran-mediated interbacterial aggregation between dextran-synthesizing streptococci and Actinomyces viscosus.", "content": "Streptococcus sanguis and Streptococcus mutans bind to the surface of Actinomyces viscosus, producing large microbial aggregates. Aggregates form rapidly and are not easily dissociated by vigorous mixing. The binding is mediated by dextran. Glucose-grown streptococci will not aggregate unless they are first mixed with high-molecular-weight dextran. Aggregation is induced with dextrans isolated from Leuconostoc, S. sanguis, or S. mutans. Sucrose-grown streptococci will adhere to A. viscosus without the addition of an exogenous source of dextran. A. viscosus will bind dextran and then bind glucose-grown streptococci. Aggregation occurs over a wide pH range and is dependent on cations. The aggregating activity of A. viscosus is both protease and heat sensitive. The aggregating activity of S. sanguis is heat stable but sensitive to dextranase.", "contents": "Dextran-mediated interbacterial aggregation between dextran-synthesizing streptococci and Actinomyces viscosus. Streptococcus sanguis and Streptococcus mutans bind to the surface of Actinomyces viscosus, producing large microbial aggregates. Aggregates form rapidly and are not easily dissociated by vigorous mixing. The binding is mediated by dextran. Glucose-grown streptococci will not aggregate unless they are first mixed with high-molecular-weight dextran. Aggregation is induced with dextrans isolated from Leuconostoc, S. sanguis, or S. mutans. Sucrose-grown streptococci will adhere to A. viscosus without the addition of an exogenous source of dextran. A. viscosus will bind dextran and then bind glucose-grown streptococci. Aggregation occurs over a wide pH range and is dependent on cations. The aggregating activity of A. viscosus is both protease and heat sensitive. The aggregating activity of S. sanguis is heat stable but sensitive to dextranase."} {"id": "PMID:1279005", "title": "Establishment of cutaneous Leishmania enriettii infection in hamsters.", "content": "A model of a self-healing type of cutaneous leishmaniasis was established in hamsters using the guinea pig parasite Leishmania enriettii. L. enriettii was passaged several times in hamsters without losing its infectivity for guinea pigs or for hamsters. The course of the infection in hamsters resembled that of guinea pigs, with the exception that the lesion at the site of parasite inoculation did not ulcerate and no metastatic lesions developed spontaneously. Moreover, unlike guinea pigs, infected or recovered hamsters were skin test unresponsive to various preparations of L. enriettii antigens. However, histological examination of draining lymph nodes showed features of a cell-mediated immune response, and in vitro inhibition of macrophage migration was demonstrable using peritoneal exudate cells from recovered animals and specific leishmanial antigen. Antibody was demonstrable by indirect immunofluorescence starting 1 week after infection. Recovered animals were immune to reinfection; however, the passive transfer of peritoneal exudate cells or serum from recovered animals did not confer protection against L. enriettii infection in normal animals.", "contents": "Establishment of cutaneous Leishmania enriettii infection in hamsters. A model of a self-healing type of cutaneous leishmaniasis was established in hamsters using the guinea pig parasite Leishmania enriettii. L. enriettii was passaged several times in hamsters without losing its infectivity for guinea pigs or for hamsters. The course of the infection in hamsters resembled that of guinea pigs, with the exception that the lesion at the site of parasite inoculation did not ulcerate and no metastatic lesions developed spontaneously. Moreover, unlike guinea pigs, infected or recovered hamsters were skin test unresponsive to various preparations of L. enriettii antigens. However, histological examination of draining lymph nodes showed features of a cell-mediated immune response, and in vitro inhibition of macrophage migration was demonstrable using peritoneal exudate cells from recovered animals and specific leishmanial antigen. Antibody was demonstrable by indirect immunofluorescence starting 1 week after infection. Recovered animals were immune to reinfection; however, the passive transfer of peritoneal exudate cells or serum from recovered animals did not confer protection against L. enriettii infection in normal animals."} {"id": "PMID:1279006", "title": "Interferon preparations enhance phagocytosis in vivo.", "content": "Previous studies have shown that interferon (IF) preparations enhance phagocytic activity in cultured mouse peritoneal macrophages. It is shown here that cell culture fluids containing large amounts of IF, which had been treated with acid and clarified of the inducer, Newcastle disease virus, enhanced phagocytic activity when injected into mice. Enhanced phagocytic activity also was observed after injection of Newcastle disease virus into mice, but the contribution of IF to this event was unclear. The kinetics of the phagocytic response to inducers in vivo were biphasic. Depression of phagocytosis occurred around 16 to 18 h after injection of Newcastle disease virus. The observed enhancement began about 12 h later and lasted for at least 60 h more. It was concluded that the complexity of the response of mice to an inducer makes analysis of the role of IF in the ensuing events difficult. However, because of documented phagocytosis-enhancing effects of IF in vitro, it is very likely that the in vivo effects observed here are to some degree mediated by IF. On this basis, the concept of the activity of IF as a lymphokine is potentially expanded.", "contents": "Interferon preparations enhance phagocytosis in vivo. Previous studies have shown that interferon (IF) preparations enhance phagocytic activity in cultured mouse peritoneal macrophages. It is shown here that cell culture fluids containing large amounts of IF, which had been treated with acid and clarified of the inducer, Newcastle disease virus, enhanced phagocytic activity when injected into mice. Enhanced phagocytic activity also was observed after injection of Newcastle disease virus into mice, but the contribution of IF to this event was unclear. The kinetics of the phagocytic response to inducers in vivo were biphasic. Depression of phagocytosis occurred around 16 to 18 h after injection of Newcastle disease virus. The observed enhancement began about 12 h later and lasted for at least 60 h more. It was concluded that the complexity of the response of mice to an inducer makes analysis of the role of IF in the ensuing events difficult. However, because of documented phagocytosis-enhancing effects of IF in vitro, it is very likely that the in vivo effects observed here are to some degree mediated by IF. On this basis, the concept of the activity of IF as a lymphokine is potentially expanded."} {"id": "PMID:1279007", "title": "Presence of pili in species of human and animal parasites and pathogens of the genuscorynebacterium.", "content": "The presence of pili in human and animal parasites and pathogens of the genus Corynebacterium was examined. C. kutscheri, C. diphtheriae, and C. pseudodiphtheriticum possessed a fairly large number of pili, ranging from dozens to more than a hundred, in 91 to 100% of the bacterial cells. C. equi, C. hoagii, C. xerosis, C. pyogenes, and C. murisepticum had only a small number of pili in 10 to 37% of the bacterial cells. In C. bovis, C. striatum, and C. pseudotuberculosis, pili were detected in only 0.5% to 3% of the bacterial cells. The pili were similar to each other and to those of C. renale; they were not rigid and had a tendency to form bundles. The length of pili usually ranged from 0.2 to 3 mum, and their diameter was within a 2- to 6-nm range.", "contents": "Presence of pili in species of human and animal parasites and pathogens of the genuscorynebacterium. The presence of pili in human and animal parasites and pathogens of the genus Corynebacterium was examined. C. kutscheri, C. diphtheriae, and C. pseudodiphtheriticum possessed a fairly large number of pili, ranging from dozens to more than a hundred, in 91 to 100% of the bacterial cells. C. equi, C. hoagii, C. xerosis, C. pyogenes, and C. murisepticum had only a small number of pili in 10 to 37% of the bacterial cells. In C. bovis, C. striatum, and C. pseudotuberculosis, pili were detected in only 0.5% to 3% of the bacterial cells. The pili were similar to each other and to those of C. renale; they were not rigid and had a tendency to form bundles. The length of pili usually ranged from 0.2 to 3 mum, and their diameter was within a 2- to 6-nm range."} {"id": "PMID:1279014", "title": "Ampicillin polymers as elicitors of passive cutaneous anaphylaxis.", "content": "The ability of ampicillin polymers to elicit passive cutaneous anaphylaxis (PCA) reactions in guinea pigs was analyzed. Mediating antibodies were raised in rabbits against a crude preparation of 6-aminopenicillanic acid (6-APA). It was found that large ampicillin polymers were potent elicitors, 1,000-fold better than benzylpenicillin polymers. Small polymers in high concentrations did not elicit PCA reactions but inhibited the activity of the larger polymers. This inhibition was more pronounced that that of ampicillin monomer. High molecular weight of ampicillin polymer in the amount of 0.1% in an ampicillin solution manifested its PCA activity. The tendency of ampicillin to polymerize, particularly when kept in solution, makes this observation worth considering. The PCA reactions described were penicilloyl-specific as verified by immunosorbent experiments.", "contents": "Ampicillin polymers as elicitors of passive cutaneous anaphylaxis. The ability of ampicillin polymers to elicit passive cutaneous anaphylaxis (PCA) reactions in guinea pigs was analyzed. Mediating antibodies were raised in rabbits against a crude preparation of 6-aminopenicillanic acid (6-APA). It was found that large ampicillin polymers were potent elicitors, 1,000-fold better than benzylpenicillin polymers. Small polymers in high concentrations did not elicit PCA reactions but inhibited the activity of the larger polymers. This inhibition was more pronounced that that of ampicillin monomer. High molecular weight of ampicillin polymer in the amount of 0.1% in an ampicillin solution manifested its PCA activity. The tendency of ampicillin to polymerize, particularly when kept in solution, makes this observation worth considering. The PCA reactions described were penicilloyl-specific as verified by immunosorbent experiments."} {"id": "PMID:1279015", "title": "Effect of season of immunization of the induction of delayed contact sensitivity in the guinea pig.", "content": "The degree of delayed contact sensitivity induced in guinea pigs was greater when sensitization was attempted in winter than when attempted in spring and summer.", "contents": "Effect of season of immunization of the induction of delayed contact sensitivity in the guinea pig. The degree of delayed contact sensitivity induced in guinea pigs was greater when sensitization was attempted in winter than when attempted in spring and summer."} {"id": "PMID:1279016", "title": "Allergen extract of horse hair and dandruff. Quantitative immunoelectrophoretic characterization of the antigens.", "content": "Freeze-dried extract of horse hair and dandruff was obtained by extraction, centrifugation, dialysis and freeze-drying. Quantitative immunoelectrophoresis using rabbit antibodies revealed the extract to be composed of 25 antigens of which some were mutually partial identical; 4 were serum-specific and non showed partial identity to solubilized hair proteins. Partial identity to antigens to serum and extract from hair and dandruff of cow, dog, cat, guinea pig, and of extract from house duct was demonstrated. After subjecting the extract to dialysis, ultrafiltration, freeze-drying and storage below 37degreesC for not more than 24 h the antigenic stability and the allergenic activity were unaffected. The effect of enzymatic degradation of the individual proteins with regard to antigenic stability and allergenic activity was also examined.", "contents": "Allergen extract of horse hair and dandruff. Quantitative immunoelectrophoretic characterization of the antigens. Freeze-dried extract of horse hair and dandruff was obtained by extraction, centrifugation, dialysis and freeze-drying. Quantitative immunoelectrophoresis using rabbit antibodies revealed the extract to be composed of 25 antigens of which some were mutually partial identical; 4 were serum-specific and non showed partial identity to solubilized hair proteins. Partial identity to antigens to serum and extract from hair and dandruff of cow, dog, cat, guinea pig, and of extract from house duct was demonstrated. After subjecting the extract to dialysis, ultrafiltration, freeze-drying and storage below 37degreesC for not more than 24 h the antigenic stability and the allergenic activity were unaffected. The effect of enzymatic degradation of the individual proteins with regard to antigenic stability and allergenic activity was also examined."} {"id": "PMID:1279017", "title": "Identification of allergens in extract of horse hair and dandruff by means of crossed radioimmunoelectrophoresis.", "content": "Sera from 26 patients and 4 normals were examined for specific IgE binding to antigens of extract of horse hair and dandruff by means of CRIE. 22 of the patients were RAST- and intracutaneous-positive to horse extract. 4 more of the patients were RAST-negative to horse allergens, but showed allergies to extract of allergens from sources other than horse. The remaining four sera from controls were RAST-negative to horse and had no history of allergy. Antigens of horse hair and dandruff showed a significantly higher degree of binding to specific IgE in the sera from the first group of patients than was the case for the two other groups. A linear correlation between specific IgE binding in RAST and in CRIE was found for the first group of patients. On the basis of these results the major allergens of the examined extract of horse hair and dandruff were identified.", "contents": "Identification of allergens in extract of horse hair and dandruff by means of crossed radioimmunoelectrophoresis. Sera from 26 patients and 4 normals were examined for specific IgE binding to antigens of extract of horse hair and dandruff by means of CRIE. 22 of the patients were RAST- and intracutaneous-positive to horse extract. 4 more of the patients were RAST-negative to horse allergens, but showed allergies to extract of allergens from sources other than horse. The remaining four sera from controls were RAST-negative to horse and had no history of allergy. Antigens of horse hair and dandruff showed a significantly higher degree of binding to specific IgE in the sera from the first group of patients than was the case for the two other groups. A linear correlation between specific IgE binding in RAST and in CRIE was found for the first group of patients. On the basis of these results the major allergens of the examined extract of horse hair and dandruff were identified."} {"id": "PMID:1279018", "title": "Isolation and partial characterization of three major allergens of horse hair and dandruff.", "content": "Three major allergens of horse hair and dandruff have been isolated. The fractionation procedures involved various combinations, described in detail, of ethanol precipitation below --5degreesC, cation- and anion-exchange chromatography, and gel filtration. UV absorption, quantitative immunoelectrophoresis and RAST inhibition were used to monitor the separations. Protein impurities constituted less than 5% in all cases. The molecular weights of the isolated proteins were 1.9 X 10(4), 5.1 X 10(4) and 3.1 X 10(4) daltons, respectively. The pIs were determined as 4.1, 3.8 and 3.9, respectively. The amino acid analysis of the isolated allergens revealed large variations in their amino acid composition which might explain different reactivities in RAST experiments. The allergenic activities of the isolated antigens were determined by RAST inhibition and prick tests.", "contents": "Isolation and partial characterization of three major allergens of horse hair and dandruff. Three major allergens of horse hair and dandruff have been isolated. The fractionation procedures involved various combinations, described in detail, of ethanol precipitation below --5degreesC, cation- and anion-exchange chromatography, and gel filtration. UV absorption, quantitative immunoelectrophoresis and RAST inhibition were used to monitor the separations. Protein impurities constituted less than 5% in all cases. The molecular weights of the isolated proteins were 1.9 X 10(4), 5.1 X 10(4) and 3.1 X 10(4) daltons, respectively. The pIs were determined as 4.1, 3.8 and 3.9, respectively. The amino acid analysis of the isolated allergens revealed large variations in their amino acid composition which might explain different reactivities in RAST experiments. The allergenic activities of the isolated antigens were determined by RAST inhibition and prick tests."} {"id": "PMID:1279019", "title": "A solid-phase radioassay for the detection of anti-thyroglobulin antibodies in different immunoglobulin classes.", "content": "A convenient technique suitable for the routine estimation of IgG and IgA anti-thyroglobulin antibodies has been devised. The assay involves the binding of anti-thyroglobulin to human thyroglobulin linked to the surface of plastic tubes; the amount of antibody bound is then determined by adding radiolabelled anti-human IgG or IgA. IgG antibody was raised in virtually all patients and significantly elevated levels of IgA antibody were also found in some patients. The test should prove helpful in diagnosis and provide quantitative evaluation of research studies.", "contents": "A solid-phase radioassay for the detection of anti-thyroglobulin antibodies in different immunoglobulin classes. A convenient technique suitable for the routine estimation of IgG and IgA anti-thyroglobulin antibodies has been devised. The assay involves the binding of anti-thyroglobulin to human thyroglobulin linked to the surface of plastic tubes; the amount of antibody bound is then determined by adding radiolabelled anti-human IgG or IgA. IgG antibody was raised in virtually all patients and significantly elevated levels of IgA antibody were also found in some patients. The test should prove helpful in diagnosis and provide quantitative evaluation of research studies."} {"id": "PMID:1279020", "title": "Role of sensitized cells in antitubular basement membrane interstitial nephritis.", "content": "The pathogenic effect of antitubular basement membrane (TBM) antibodies in anti-TBM interstitial nephritis has been demonstrated. To determine the relative role of sensitized cells in inducing this lesion, lymph node cells (LNC) alone or a combination of LNC and peritoneal exudate cells were transferred from Brown Norway (BN) rats, previously immunized with TBM into unimmunized BN-recipient rats. Cells were transferred directly under the recipients' renal capsules. Although significant tubular lesions were induced by the cells, the lesions were usually mild and always focal. Hence, sensitized cells do not appear to be central to the pathogenesis of anti-TBM nephritis.", "contents": "Role of sensitized cells in antitubular basement membrane interstitial nephritis. The pathogenic effect of antitubular basement membrane (TBM) antibodies in anti-TBM interstitial nephritis has been demonstrated. To determine the relative role of sensitized cells in inducing this lesion, lymph node cells (LNC) alone or a combination of LNC and peritoneal exudate cells were transferred from Brown Norway (BN) rats, previously immunized with TBM into unimmunized BN-recipient rats. Cells were transferred directly under the recipients' renal capsules. Although significant tubular lesions were induced by the cells, the lesions were usually mild and always focal. Hence, sensitized cells do not appear to be central to the pathogenesis of anti-TBM nephritis."} {"id": "PMID:1279021", "title": "Inflammation-inducing factors from human lymphocytes. Correlation with polymorphonuclear leucocyte migration enhancement of inhibition.", "content": "Factors capable of inducing inflammatory reactions in the skin of normal guinea pigs have been demonstrated in culture supernatants from PPD-stimulated human mononuclear cells from tuberculin-positive donors. The reaction is characterised by erythema, induration and infiltration with mononuclear cells and some polymorphonuclear leucocytes. These supernatants either enhance or do not affect polymorph migration in the leucocyte migration test. Supernatants that inhibit migration in vitro produce a marked polymorph infiltration upon intradermal injection.", "contents": "Inflammation-inducing factors from human lymphocytes. Correlation with polymorphonuclear leucocyte migration enhancement of inhibition. Factors capable of inducing inflammatory reactions in the skin of normal guinea pigs have been demonstrated in culture supernatants from PPD-stimulated human mononuclear cells from tuberculin-positive donors. The reaction is characterised by erythema, induration and infiltration with mononuclear cells and some polymorphonuclear leucocytes. These supernatants either enhance or do not affect polymorph migration in the leucocyte migration test. Supernatants that inhibit migration in vitro produce a marked polymorph infiltration upon intradermal injection."} {"id": "PMID:1279022", "title": "Adjuvant effect of lysolecithin analogues on the development of contact sensitivity in mice.", "content": "The influence of two lysolecithin analogues on the development of contact sensitivity (CS) to picryl chloride in mice was studied. Both substances were shown to have an adjuvant effect on the primary CS response, but depending on dosage of adjuvant and antigen, the timing of adjuvant injection, and the strain of mice employed, the relative activities of the two substances varied considerably. Large amounts of one of the adjuvants were less stimulatory than small amounts. Both substances had a suppressive effect on the development of CS following repeated administration of picryl chloride. The results are discussed in relation to hypotheses on the cellular targets for, and mode of action of, immunological adjuvants.", "contents": "Adjuvant effect of lysolecithin analogues on the development of contact sensitivity in mice. The influence of two lysolecithin analogues on the development of contact sensitivity (CS) to picryl chloride in mice was studied. Both substances were shown to have an adjuvant effect on the primary CS response, but depending on dosage of adjuvant and antigen, the timing of adjuvant injection, and the strain of mice employed, the relative activities of the two substances varied considerably. Large amounts of one of the adjuvants were less stimulatory than small amounts. Both substances had a suppressive effect on the development of CS following repeated administration of picryl chloride. The results are discussed in relation to hypotheses on the cellular targets for, and mode of action of, immunological adjuvants."} {"id": "PMID:1279023", "title": "Modulation of the immune response by passive antibodies. II. Effects of passive anti-hapten and anti-carrier antibodies on the immune response to a sustained antigenic stimulation.", "content": "The present work is an attempt at understanding the modulating effects of passive antibodies on the immune response to a sustained antigenic stimulation. Passive anti-carrier and anti-hapten antibodies were injected 24 h before immunization with the hapten carrier conjugate into guinea pigs subsequently injected intradermally with the carrier alone on days 11 and 23. The results showed that passive anti-carrier antibodies blocked the effects of intradermal injections of carrier, i.e., desensitization and increase of antibody synthesis to the carrier. Passive anti-hapten antibodies did not prevent desensitization and delayed antibody synthesis to the carrier. The mechanisms whereby passive antibodies modulate the response to a sustained antigenic stimulation are discussed.", "contents": "Modulation of the immune response by passive antibodies. II. Effects of passive anti-hapten and anti-carrier antibodies on the immune response to a sustained antigenic stimulation. The present work is an attempt at understanding the modulating effects of passive antibodies on the immune response to a sustained antigenic stimulation. Passive anti-carrier and anti-hapten antibodies were injected 24 h before immunization with the hapten carrier conjugate into guinea pigs subsequently injected intradermally with the carrier alone on days 11 and 23. The results showed that passive anti-carrier antibodies blocked the effects of intradermal injections of carrier, i.e., desensitization and increase of antibody synthesis to the carrier. Passive anti-hapten antibodies did not prevent desensitization and delayed antibody synthesis to the carrier. The mechanisms whereby passive antibodies modulate the response to a sustained antigenic stimulation are discussed."} {"id": "PMID:1279024", "title": "Binding of morphine by serum globulins from morphine-treated rabbits. I. Induction and measurement of binding.", "content": "Treatment of rabbits with morphine under conditions defined in this report leads to significant and reproducible increases in the binding of morphine by serum globulins. Complexes formed are readily dissociable so that the conditions employed in measuring binding become critical. The data presented document the effects of several variables upon the results of binding measurements. Also described are treatments that lead either to \"priming\" or to the inhibition of a subsequent response.", "contents": "Binding of morphine by serum globulins from morphine-treated rabbits. I. Induction and measurement of binding. Treatment of rabbits with morphine under conditions defined in this report leads to significant and reproducible increases in the binding of morphine by serum globulins. Complexes formed are readily dissociable so that the conditions employed in measuring binding become critical. The data presented document the effects of several variables upon the results of binding measurements. Also described are treatments that lead either to \"priming\" or to the inhibition of a subsequent response."} {"id": "PMID:1279025", "title": "Heterogeneity of rabbit homologous skin sensitizing antibodies: IgE and a new subclass IgGa.", "content": "Homologous skin sensitizing antibodies in the rabbit can be differentiated by their requirement for complement in expressing the passive cutaneous anaphylactic reaction as complement dependent (CD) or complement independent (CI). CI antibodies are representative of the IgE class, while the CD antibodies belong to a proposed new subclass of IgG designated IgGa (a = anaphylaxis). The following are characteristics of CI (IgE) antibodies: elution at 0.05 M on DEAE at pH 8.1 migration ahead of 7S in ultracentrifugation, molecular weight 215,000 daltons by Sephadex G-200, fast gamma-electrophoretic mobility, isoelectric point, pI = 4.98 (5.68-4.58), 85-95% heat sensitivity, sensitivity to reduction plus alkylation and option at 0.01 M on DEAE, 7S in ultracentrifugation, MW 138,000 daltons, slow gamma-electrophoretic mobility pI = 6.90 (8.30-5.70), resistance to heating and to reduction plus alkylation and 1-day optimal SP. CI antibodies could be absorbed by anti-Fab, anti-epsilon, the homologous antigen and were not absorbed by anti-gamma, anti-alpha, or heterologous antigens. The CD antibodies were absorbed by anti-Fab, anti-gamma and not absorbed by anti-epsilon, anti-alpha, or heterologous antigens.", "contents": "Heterogeneity of rabbit homologous skin sensitizing antibodies: IgE and a new subclass IgGa. Homologous skin sensitizing antibodies in the rabbit can be differentiated by their requirement for complement in expressing the passive cutaneous anaphylactic reaction as complement dependent (CD) or complement independent (CI). CI antibodies are representative of the IgE class, while the CD antibodies belong to a proposed new subclass of IgG designated IgGa (a = anaphylaxis). The following are characteristics of CI (IgE) antibodies: elution at 0.05 M on DEAE at pH 8.1 migration ahead of 7S in ultracentrifugation, molecular weight 215,000 daltons by Sephadex G-200, fast gamma-electrophoretic mobility, isoelectric point, pI = 4.98 (5.68-4.58), 85-95% heat sensitivity, sensitivity to reduction plus alkylation and option at 0.01 M on DEAE, 7S in ultracentrifugation, MW 138,000 daltons, slow gamma-electrophoretic mobility pI = 6.90 (8.30-5.70), resistance to heating and to reduction plus alkylation and 1-day optimal SP. CI antibodies could be absorbed by anti-Fab, anti-epsilon, the homologous antigen and were not absorbed by anti-gamma, anti-alpha, or heterologous antigens. The CD antibodies were absorbed by anti-Fab, anti-gamma and not absorbed by anti-epsilon, anti-alpha, or heterologous antigens."} {"id": "PMID:1279026", "title": "Receptors for antibody-opsonic adherence on the eosinophils of guinea pigs.", "content": "Eosinophils have recently been implicated in antibody-dependent cell-mediated damage to schistosomula. Because of this, eosinophils of the guinea pig have been examined for surface receptors capable of giving antibody opsonic adherence; a rosetting reaction has been used. The eosinophils were shown to possess Fc receptors for homologous immunoglobulin. No selective difference between IgG1 and IgG2 was observed. In marked contrast to macrophages, guinea pig eosinophils failed to show opsonic adherence to red cells sensitized to a comparable degree with rabbit antibody. With red cell antibodies made in the pig, however, the reciprocal situation held, namely opsonic adherence was stronger with eosinophils than with macrophages.", "contents": "Receptors for antibody-opsonic adherence on the eosinophils of guinea pigs. Eosinophils have recently been implicated in antibody-dependent cell-mediated damage to schistosomula. Because of this, eosinophils of the guinea pig have been examined for surface receptors capable of giving antibody opsonic adherence; a rosetting reaction has been used. The eosinophils were shown to possess Fc receptors for homologous immunoglobulin. No selective difference between IgG1 and IgG2 was observed. In marked contrast to macrophages, guinea pig eosinophils failed to show opsonic adherence to red cells sensitized to a comparable degree with rabbit antibody. With red cell antibodies made in the pig, however, the reciprocal situation held, namely opsonic adherence was stronger with eosinophils than with macrophages."} {"id": "PMID:1279027", "title": "In vitro lymphocyte response to the phytomitogens in untreated and treated patients with Hodgkin's disease.", "content": "In vitro lymphocyte response to phytohemagglutinins (PHA), concavalin A (Con A), and pokeweed mitogen (PW) was evaluated in untreated and treated patients with Hodgkin's disease (HD). The responding capacity to PHA was depressed, though not constantly, in the untreated patients compared with the response to lymphocytes from normal individuals. The depression was more evident, at group level, when the cells were stimulated with suboptimal concentrations of PHA. Radiotherapy constantly induced a strong decrease or a complete loss of the responding capacity of the cells which persisted at low levels for many months. Some years after the initial course of treatment, the response was clearly depressed, but it was better in patients in remission than during relapse. Splenectomy did not affect the responding capacity of the cells. The depressive effect induced by chemotherapy was apparently less marked and persistent than that of radiation. Con A- and PW-induced lymphocyte transformation usually paralleled the PHA-induced response. The depressed response to PHA was not due to an inhibitory activity of HD serum. Washed HD lymphocytes in fetal calf serum were not stimulated better than in autologous plasma, nor were HD sera able to depress the response of normal lymphocytes to PHA, Con A, PW, and PPD. Supernatants from HD lymphocytes cultured for 24 h without any stimulant, and extracts of these cells were also unable to affect the response of normal lymphocytes to PHA.", "contents": "In vitro lymphocyte response to the phytomitogens in untreated and treated patients with Hodgkin's disease. In vitro lymphocyte response to phytohemagglutinins (PHA), concavalin A (Con A), and pokeweed mitogen (PW) was evaluated in untreated and treated patients with Hodgkin's disease (HD). The responding capacity to PHA was depressed, though not constantly, in the untreated patients compared with the response to lymphocytes from normal individuals. The depression was more evident, at group level, when the cells were stimulated with suboptimal concentrations of PHA. Radiotherapy constantly induced a strong decrease or a complete loss of the responding capacity of the cells which persisted at low levels for many months. Some years after the initial course of treatment, the response was clearly depressed, but it was better in patients in remission than during relapse. Splenectomy did not affect the responding capacity of the cells. The depressive effect induced by chemotherapy was apparently less marked and persistent than that of radiation. Con A- and PW-induced lymphocyte transformation usually paralleled the PHA-induced response. The depressed response to PHA was not due to an inhibitory activity of HD serum. Washed HD lymphocytes in fetal calf serum were not stimulated better than in autologous plasma, nor were HD sera able to depress the response of normal lymphocytes to PHA, Con A, PW, and PPD. Supernatants from HD lymphocytes cultured for 24 h without any stimulant, and extracts of these cells were also unable to affect the response of normal lymphocytes to PHA."} {"id": "PMID:1279028", "title": "Imitation in the family: a study of older parents and their adult sons.", "content": "Older parents and their adult sons (fifteen father-mother-son triads) participated in this study which investigated whether imitative behavior is prominent in these families and whether interpersonal perceptions are related to the degree of imitation. Both perceptual and moral imitation tasks were used and personality descriptions were obtained on dimensions of activity, potency, and evaluation. Adult sons were found to imitate their parents on both tasks and particularly their fathers on moral issues. Older parents also were found to imitate their sons in a possible \"reversal\" of the direction of identification. Differential patterns of interpersonal perceptions were related to imitation for the three groups. Potential theoretical explanations are discussed.", "contents": "Imitation in the family: a study of older parents and their adult sons. Older parents and their adult sons (fifteen father-mother-son triads) participated in this study which investigated whether imitative behavior is prominent in these families and whether interpersonal perceptions are related to the degree of imitation. Both perceptual and moral imitation tasks were used and personality descriptions were obtained on dimensions of activity, potency, and evaluation. Adult sons were found to imitate their parents on both tasks and particularly their fathers on moral issues. Older parents also were found to imitate their sons in a possible \"reversal\" of the direction of identification. Differential patterns of interpersonal perceptions were related to imitation for the three groups. Potential theoretical explanations are discussed."} {"id": "PMID:1279029", "title": "The ecology of adaptation to a new environment.", "content": "The intrainstitutional room transfer of 48 elderly residents was studied by direct behavior-mapping techniques. Data were obtained on the physical location, body position, and behavior of both residents and staff on a large number of tours of residential floors preceding and following the move. About half of the hypotheses suggesting that greater passivity and restriction in social space would occur following the move were supported. These responses were seen as adaptive in allowing the individual to comprehend the new environment prior to moving out more actively.", "contents": "The ecology of adaptation to a new environment. The intrainstitutional room transfer of 48 elderly residents was studied by direct behavior-mapping techniques. Data were obtained on the physical location, body position, and behavior of both residents and staff on a large number of tours of residential floors preceding and following the move. About half of the hypotheses suggesting that greater passivity and restriction in social space would occur following the move were supported. These responses were seen as adaptive in allowing the individual to comprehend the new environment prior to moving out more actively."} {"id": "PMID:1279030", "title": "The impact of housing relocation on the elderly: an alternative methodological approach.", "content": "This article examines the impact of housing relocation on the patterns of interaction and life satisfaction of a sample of older, married adults living in an urban area of central Arkansas. Interviews were conducted with 115 individuals residing in congregate housing and with a matched sample of 105 persons living in independent residential units. Respondents in the two settings fail to demonstrate significant differences in frequencies of social interaction. Patterns of interaction in five specific areas also reveal no appreciable variation. In addition, the time-related effects of congregate dwelling are suggestive but not confirming of negative changes in both interaction and satisfaction. On the other hand, regardless of residential duration, health, sex or age, independent residents exhibit higher life satisfaction. The data suggest the congregate setting to possess insufficient resources to offset the objective and subjective decrements of old age.", "contents": "The impact of housing relocation on the elderly: an alternative methodological approach. This article examines the impact of housing relocation on the patterns of interaction and life satisfaction of a sample of older, married adults living in an urban area of central Arkansas. Interviews were conducted with 115 individuals residing in congregate housing and with a matched sample of 105 persons living in independent residential units. Respondents in the two settings fail to demonstrate significant differences in frequencies of social interaction. Patterns of interaction in five specific areas also reveal no appreciable variation. In addition, the time-related effects of congregate dwelling are suggestive but not confirming of negative changes in both interaction and satisfaction. On the other hand, regardless of residential duration, health, sex or age, independent residents exhibit higher life satisfaction. The data suggest the congregate setting to possess insufficient resources to offset the objective and subjective decrements of old age."} {"id": "PMID:1279031", "title": "The health status and the health care problems of the aged in an Italian community.", "content": "This study had the purpose of identifying the health needs of the elderly population of a small urban Italian community for the purpose of planning sociomedical services. The data were collected by interviewing a stratified random sample of 1291 individuals over sixty years of age. About one third sample reported poor health. However, health complaints, both physical and mental, were particularly common among the persons living in disadvantaged social and economic conditions. The great majority of the respondents were found to be self-sufficient, and ambulatory. The results indicate that the present health needs of the elderly living in the community require new health services, such as home care, which will permit the elderly to avoid future hospitalization.", "contents": "The health status and the health care problems of the aged in an Italian community. This study had the purpose of identifying the health needs of the elderly population of a small urban Italian community for the purpose of planning sociomedical services. The data were collected by interviewing a stratified random sample of 1291 individuals over sixty years of age. About one third sample reported poor health. However, health complaints, both physical and mental, were particularly common among the persons living in disadvantaged social and economic conditions. The great majority of the respondents were found to be self-sufficient, and ambulatory. The results indicate that the present health needs of the elderly living in the community require new health services, such as home care, which will permit the elderly to avoid future hospitalization."} {"id": "PMID:1279032", "title": "Age, anxiety, and self-reported health.", "content": "A sample of 472 normal males ranging in age from twenty-five to eighty-two was divided into anxious and adjusted groups on the basis of a cluster analysis of the Cattell 16PF test, and compared for scores on a self-report measure of health. While the anxious men reported more symptoms than the adjusted in the young and middle age groups, there was no difference in the old group. Although anxiety was found to be unrelated to health as evaluated by physicians' examinations, the anxious men indeed reported more health problems in eight major areas of health concern than was warranted by their actual physical health status. This relation also did not hold in the old group. Anxious men seemed to be more vagilant about their health in young and middle age groups, but not in the old group. This was interpreted as a defensive denial of symptoms in the old anxious group; for a person with trait anxiety, anxiety about approaching death and increasing health problems is just too much to bear, and he resorts to denying symptoms in an effort to diminish his anxiety.", "contents": "Age, anxiety, and self-reported health. A sample of 472 normal males ranging in age from twenty-five to eighty-two was divided into anxious and adjusted groups on the basis of a cluster analysis of the Cattell 16PF test, and compared for scores on a self-report measure of health. While the anxious men reported more symptoms than the adjusted in the young and middle age groups, there was no difference in the old group. Although anxiety was found to be unrelated to health as evaluated by physicians' examinations, the anxious men indeed reported more health problems in eight major areas of health concern than was warranted by their actual physical health status. This relation also did not hold in the old group. Anxious men seemed to be more vagilant about their health in young and middle age groups, but not in the old group. This was interpreted as a defensive denial of symptoms in the old anxious group; for a person with trait anxiety, anxiety about approaching death and increasing health problems is just too much to bear, and he resorts to denying symptoms in an effort to diminish his anxiety."} {"id": "PMID:1279033", "title": "\". . . Change and sameness . . .\" reconsidered.", "content": "This paper acknowledges and responds to Jack Block's statistical critique of the author's previously reported study of changes and sameness in personality development. The critique was apt, and calls attention to the difficulty of working appropriately with numerous, multiply-assessed variables. A re-analysis of the data is presented here. The general pattern of findings remains consistent with the original interpretations, but the re-analysis produced some differences as well.", "contents": "\". . . Change and sameness . . .\" reconsidered. This paper acknowledges and responds to Jack Block's statistical critique of the author's previously reported study of changes and sameness in personality development. The critique was apt, and calls attention to the difficulty of working appropriately with numerous, multiply-assessed variables. A re-analysis of the data is presented here. The general pattern of findings remains consistent with the original interpretations, but the re-analysis produced some differences as well."} {"id": "PMID:1279034", "title": "Resistance to isolation among elderly widows.", "content": "The widow's ability to resist isolation in old age-to either maintain the involvement of earlier years or develop new social networks-may be conditioned by a number of different factors. Drawing upon a survey of 409 widows, age sixty-five and older, from the Piedmont region of South Carolina, this study concludes that good health and the availability of economic resources are the primary factors which facilitate involvement with family, neighbors and friends, and participation in a number and variety of daily activities. In addition, those widows who were more educated participated in more activities; those living in small towns and rural areas were more involved with family and friends; and white widows saw more of their children, while black respondents were more active and knew more of their neighbors. Finally, the availability and degree of contact with children was unrelated to other activities, while friendship and neighboring was positively associated with taking walks, shopping, and attendance at religious services and other organizational meetings.", "contents": "Resistance to isolation among elderly widows. The widow's ability to resist isolation in old age-to either maintain the involvement of earlier years or develop new social networks-may be conditioned by a number of different factors. Drawing upon a survey of 409 widows, age sixty-five and older, from the Piedmont region of South Carolina, this study concludes that good health and the availability of economic resources are the primary factors which facilitate involvement with family, neighbors and friends, and participation in a number and variety of daily activities. In addition, those widows who were more educated participated in more activities; those living in small towns and rural areas were more involved with family and friends; and white widows saw more of their children, while black respondents were more active and knew more of their neighbors. Finally, the availability and degree of contact with children was unrelated to other activities, while friendship and neighboring was positively associated with taking walks, shopping, and attendance at religious services and other organizational meetings."} {"id": "PMID:1279036", "title": "The increase in working years due to elimination of cancer as a cause of death.", "content": "The relative significance of various forms of cancer in terms of causing death is analysed by estimation of the increase in person-years of working age (20-64 years) following elimination of the disease. Methods based upon the theory of competing risks are applied to the statistics on causes of death in Finland during the years 1966-70. It is estimated that if there were no lung cancer (the commonest type of cancer in both morbidity and mortality statistics in males in Finland) the annual deaths saved would yield 5,900 working years (both sexes combined). Leukaemia and cancer of the stomach would be next in rank order, with figures of respectively 4,000 and 3,900 working years more. Female cancer with the highest incidence, that of the breast, would be characterized by 2,900 additional working years. The significance of types of cancer that affect young people is stressed in these calculations: leukaemia, brain tumours and lymphomas (both sexes combined) are 6th, 12th and 11th respectively in the statistics of cancer causes of death, but 2nd, 4th and 6th respectively in the list of additional working years to be gained by elimination of the disease. On the other hand, cancer of the prostate, 3rd in males according to the annual numbers of cancer deaths, would take the 15th position for the increase in working years in males. If no risk of cancer existed, the annual deaths saved would produce 36,000 working years, a figure exceeded only by those for cardiovascular diseases (55,000 working years) and accidents (51,000 working years). The results indicate that no practical differences exist between the results derived under the assumptions of various models for competing risks, but that the exclusion of competing risks may result in considerable degrees of bias in estimation if the population has a high general mortality.", "contents": "The increase in working years due to elimination of cancer as a cause of death. The relative significance of various forms of cancer in terms of causing death is analysed by estimation of the increase in person-years of working age (20-64 years) following elimination of the disease. Methods based upon the theory of competing risks are applied to the statistics on causes of death in Finland during the years 1966-70. It is estimated that if there were no lung cancer (the commonest type of cancer in both morbidity and mortality statistics in males in Finland) the annual deaths saved would yield 5,900 working years (both sexes combined). Leukaemia and cancer of the stomach would be next in rank order, with figures of respectively 4,000 and 3,900 working years more. Female cancer with the highest incidence, that of the breast, would be characterized by 2,900 additional working years. The significance of types of cancer that affect young people is stressed in these calculations: leukaemia, brain tumours and lymphomas (both sexes combined) are 6th, 12th and 11th respectively in the statistics of cancer causes of death, but 2nd, 4th and 6th respectively in the list of additional working years to be gained by elimination of the disease. On the other hand, cancer of the prostate, 3rd in males according to the annual numbers of cancer deaths, would take the 15th position for the increase in working years in males. If no risk of cancer existed, the annual deaths saved would produce 36,000 working years, a figure exceeded only by those for cardiovascular diseases (55,000 working years) and accidents (51,000 working years). The results indicate that no practical differences exist between the results derived under the assumptions of various models for competing risks, but that the exclusion of competing risks may result in considerable degrees of bias in estimation if the population has a high general mortality."} {"id": "PMID:1279037", "title": "Concanavalin A receptors on the surface membrane of lymphocytes from patients with African Burkitt's lymphoma and lymphoma cell lines.", "content": "Lymphocytes isolated from the peripheral blood and from tumor tissues of patients with African Burkitt's lymphoma have been studied for cap formation and agglutinability by Concanavalin A (Con A). Peripheral blood from healthy adult persons served as a normal control and blood from patients with carcinoma served as a non-lymphoma control. These studies included 29 patients with Burkitt's lymphoma, 93 with carcinoma, and 105 healthy adult persons, as well as tumor tissues from 13 patients with Burkitt's lymphoma. The great majority of the carcinomas were from the face and neck regions. Lymphocytes from the blood of the majority of patients with Burkitt's lymphoma, as well as those from tumor tissues, exhibited a reduced cap-forming ability (2-6%) and increased Con-A-induced agglutinability compared to lymphocytes from healthy normal donors and from patients with carcinoma, although some of the lymphocytes from patients with carcinoma had a somewhat lower range of cap formation than the lymphocytes from healthy donors. No difference was observed in the interaction with Con A of lymphocytes from the different types of carcinoma studied. Eight lymphoid cell lines were established in our laboratory from the tumor tissues of patients with Burkitt's lymphoma. The cap-forming ability and agglutinability by Con A of these lines was examined and compared to those of the \"classical\" lymphoma lines: Raji, Daudi and P3HR1. All cell lines exhibited an increased Con-A-induced agglutinability and a reduced cap-forming ability compared to normal lymphocytes, except for P3HR1 cells which exhibited a cap-forming ability of 15-20%. These findings are discussed in relation to the association of the lymphocytes with malignancy and as a possible aid in the differential diagnosis between malignant lymphomas and other diseases.", "contents": "Concanavalin A receptors on the surface membrane of lymphocytes from patients with African Burkitt's lymphoma and lymphoma cell lines. Lymphocytes isolated from the peripheral blood and from tumor tissues of patients with African Burkitt's lymphoma have been studied for cap formation and agglutinability by Concanavalin A (Con A). Peripheral blood from healthy adult persons served as a normal control and blood from patients with carcinoma served as a non-lymphoma control. These studies included 29 patients with Burkitt's lymphoma, 93 with carcinoma, and 105 healthy adult persons, as well as tumor tissues from 13 patients with Burkitt's lymphoma. The great majority of the carcinomas were from the face and neck regions. Lymphocytes from the blood of the majority of patients with Burkitt's lymphoma, as well as those from tumor tissues, exhibited a reduced cap-forming ability (2-6%) and increased Con-A-induced agglutinability compared to lymphocytes from healthy normal donors and from patients with carcinoma, although some of the lymphocytes from patients with carcinoma had a somewhat lower range of cap formation than the lymphocytes from healthy donors. No difference was observed in the interaction with Con A of lymphocytes from the different types of carcinoma studied. Eight lymphoid cell lines were established in our laboratory from the tumor tissues of patients with Burkitt's lymphoma. The cap-forming ability and agglutinability by Con A of these lines was examined and compared to those of the \"classical\" lymphoma lines: Raji, Daudi and P3HR1. All cell lines exhibited an increased Con-A-induced agglutinability and a reduced cap-forming ability compared to normal lymphocytes, except for P3HR1 cells which exhibited a cap-forming ability of 15-20%. These findings are discussed in relation to the association of the lymphocytes with malignancy and as a possible aid in the differential diagnosis between malignant lymphomas and other diseases."} {"id": "PMID:1279038", "title": "Relapse in Burkitt's lymphoma.", "content": "Of 109 patients with histologically confirmed Burkitt's lymphoma who completed a course of chemotherapy, 86 (79%) achieved complete remission. Forty-five (52%) of patients with initial complete remission relapsed with tumour over an observation period ranging from 2 years to over 5 years. Relapse was more common in patients who initially presented with abdominal or central nervous system (CNS) involvement than in patients who presented with localized facial tumours (p less than 0.01). Anatomical distribution of tumour on relapse differed from that at presentation. Facial bones were much less frequently involved on relapse; on the other hand, the CNS, cranial nerves, orbits and skin were frequent sites of disease on relapse. CNS involvement occurred in 42% (19/45) of patients at the first relapse and in 73% (11/15) of patients with multiple relapses. Prognosis in these patients was poor. Two relapse types were clinically identifiable. Early relapse (remission duration less than 12 weeks) was associated with frequent involvement of the CNS, drug resistance and a generally unfavourable outcome. Patients with late relapse (remission duration greater than 12 weeks) responded much better to secondary treatment. Possible pathogenic mechanisms underlying these two relapse types are discussed.", "contents": "Relapse in Burkitt's lymphoma. Of 109 patients with histologically confirmed Burkitt's lymphoma who completed a course of chemotherapy, 86 (79%) achieved complete remission. Forty-five (52%) of patients with initial complete remission relapsed with tumour over an observation period ranging from 2 years to over 5 years. Relapse was more common in patients who initially presented with abdominal or central nervous system (CNS) involvement than in patients who presented with localized facial tumours (p less than 0.01). Anatomical distribution of tumour on relapse differed from that at presentation. Facial bones were much less frequently involved on relapse; on the other hand, the CNS, cranial nerves, orbits and skin were frequent sites of disease on relapse. CNS involvement occurred in 42% (19/45) of patients at the first relapse and in 73% (11/15) of patients with multiple relapses. Prognosis in these patients was poor. Two relapse types were clinically identifiable. Early relapse (remission duration less than 12 weeks) was associated with frequent involvement of the CNS, drug resistance and a generally unfavourable outcome. Patients with late relapse (remission duration greater than 12 weeks) responded much better to secondary treatment. Possible pathogenic mechanisms underlying these two relapse types are discussed."} {"id": "PMID:1279039", "title": "Experimental studies on betel nut and tobacco carcinogenicity.", "content": "Sun-dried Mangalore betel nut extracts in water and in DMSO, and sun-cured Vadakkan tobacco extract in DMSO, were tested for their carcinogenic potency. Inbred Swiss and C17 mice and golden hamsters were used for the experiments. Control animals treated with either DMSO or water did not show any changes at the sites of administration. On subcutaneous administration of betel nut extract, 60% of Swiss mice developed transplantable fibrosarcomas at the site of injection. Skin application of DMSO extracts of tobacco and of betel nut separately did not result in skin lesions in C17 mice; but when a mixed DMSO extract of tobacco and betel nut was used, skin papilloma and epidermoid carcinoma developed in some animals. Similarly, hamster cheek pouches painted with a DMSO extract of tobacco alone did not develop malignant atypia whereas those painted with a DMSO extract of betel nut showed early malignant changes. DMSO extract of a mixture of tobacco and betel nut positively increased the incidence of early malignant changes in the hamster cheek pouch, indicating the enhancing effect of betel nut in carcinogenesis.", "contents": "Experimental studies on betel nut and tobacco carcinogenicity. Sun-dried Mangalore betel nut extracts in water and in DMSO, and sun-cured Vadakkan tobacco extract in DMSO, were tested for their carcinogenic potency. Inbred Swiss and C17 mice and golden hamsters were used for the experiments. Control animals treated with either DMSO or water did not show any changes at the sites of administration. On subcutaneous administration of betel nut extract, 60% of Swiss mice developed transplantable fibrosarcomas at the site of injection. Skin application of DMSO extracts of tobacco and of betel nut separately did not result in skin lesions in C17 mice; but when a mixed DMSO extract of tobacco and betel nut was used, skin papilloma and epidermoid carcinoma developed in some animals. Similarly, hamster cheek pouches painted with a DMSO extract of tobacco alone did not develop malignant atypia whereas those painted with a DMSO extract of betel nut showed early malignant changes. DMSO extract of a mixture of tobacco and betel nut positively increased the incidence of early malignant changes in the hamster cheek pouch, indicating the enhancing effect of betel nut in carcinogenesis."} {"id": "PMID:1279040", "title": "Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats.", "content": "An experiment in which rats were injected intrapleurally with asbestos, the injection taking place at an age of either 2 or 10 months, is reported. In the former group 19 out of 48 rats developed a mesothelioma compared with 17 out of 90 in the latter group. However, by considering the two groups at equal times after injection, eliminating the effects of natural mortality and also taking into account that not all of the mesotheliomas were the cause of death, it was shown that the incidence rate of mesotheliomas was significantly higher (p less than 0.01) in the rats injected at age 10 months and the relative rate was estimated as about 4, with 95% confidence limits of 1.5 and 12. An alternative explanation that the mesotheliomas occurred in the two groups at similar rates, except that in the group injected at age 10 months they occurred on average 4 months sooner after injection, is discussed. Two other groups were also injected, one at age 17 months and the other at 22 months. In the former group two early mesotheliomas were observed, 10 and 74 days after injection, but the next was not observed until over a year later. No explanation of this finding could be suggested other than the possibility that these two tumours were not associated with the asbestos treatment.", "contents": "Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats. An experiment in which rats were injected intrapleurally with asbestos, the injection taking place at an age of either 2 or 10 months, is reported. In the former group 19 out of 48 rats developed a mesothelioma compared with 17 out of 90 in the latter group. However, by considering the two groups at equal times after injection, eliminating the effects of natural mortality and also taking into account that not all of the mesotheliomas were the cause of death, it was shown that the incidence rate of mesotheliomas was significantly higher (p less than 0.01) in the rats injected at age 10 months and the relative rate was estimated as about 4, with 95% confidence limits of 1.5 and 12. An alternative explanation that the mesotheliomas occurred in the two groups at similar rates, except that in the group injected at age 10 months they occurred on average 4 months sooner after injection, is discussed. Two other groups were also injected, one at age 17 months and the other at 22 months. In the former group two early mesotheliomas were observed, 10 and 74 days after injection, but the next was not observed until over a year later. No explanation of this finding could be suggested other than the possibility that these two tumours were not associated with the asbestos treatment."} {"id": "PMID:1279067", "title": "Ainhum: treatment with intralesional steroids.", "content": "Ainhum is a rare constricting band disease, usually affecting digits and resulting in spontaneous amputation. Prompt symptomatic relief and latter partial resolution of the fibrotic band followed intralesional steroid injection in the case presented.", "contents": "Ainhum: treatment with intralesional steroids. Ainhum is a rare constricting band disease, usually affecting digits and resulting in spontaneous amputation. Prompt symptomatic relief and latter partial resolution of the fibrotic band followed intralesional steroid injection in the case presented."} {"id": "PMID:1279071", "title": "Deep mycoses prevalent in the Igbos of Nigeria.", "content": "During a 3-year period, 6 cases of Africal histoplasmosis, 6 of phycomycosis and 5 of mycetoma were recognized histologically in 0.4 per cent of 4,307 surgical specimens removed from Nigerian Igbos and examined at a central laboratory. Undoubtedly, these cases are but the representatives of the mycological iceberg existing in this part of the world. Our experience suggests that collaboration between physicians, pathologists and mycologists should bring about increased international awareness of the deep mycoses.", "contents": "Deep mycoses prevalent in the Igbos of Nigeria. During a 3-year period, 6 cases of Africal histoplasmosis, 6 of phycomycosis and 5 of mycetoma were recognized histologically in 0.4 per cent of 4,307 surgical specimens removed from Nigerian Igbos and examined at a central laboratory. Undoubtedly, these cases are but the representatives of the mycological iceberg existing in this part of the world. Our experience suggests that collaboration between physicians, pathologists and mycologists should bring about increased international awareness of the deep mycoses."} {"id": "PMID:1279072", "title": "Straight-hair nevus syndrome: a case report with scanning electron microscopic findings of hair morphology.", "content": "Straight-hair nevus of the scalp is a distinct clinical entity. A case is reported and 2 other cases from the literature are reviewed. In our patient, specific morphology of the hair shown by scanning electron microscopy suggested a disorder in keratogenesis from loss of cuticular cells. Straight-hair nevus is probably a form of localized trichodysplasia.", "contents": "Straight-hair nevus syndrome: a case report with scanning electron microscopic findings of hair morphology. Straight-hair nevus of the scalp is a distinct clinical entity. A case is reported and 2 other cases from the literature are reviewed. In our patient, specific morphology of the hair shown by scanning electron microscopy suggested a disorder in keratogenesis from loss of cuticular cells. Straight-hair nevus is probably a form of localized trichodysplasia."} {"id": "PMID:1279082", "title": "Thermodynamic parameters of transfer of N-acetyl ethyl esters of different amino acids from organic solvents to water.", "content": "The distribution coefficients of N-acetyl ethyl esters of glycine, diglycine, beta-alanine, alanine, valine, norvaline, leucine and norleucine between water and different organic solvents have been measured at different temperatures. Similar distribution coefficients have been measured for simple amides, urea, formamide, acetamide and N-methyl acetamide. From the distribution measurements, deltaGtr, the free energy of transfer of the solutes from organic solvents to water has been calculated. The temperature dependence of the distribution coefficient values has been utilised to determine the enthalpy of transfer, deltaHtr, and entropy of transfer deltaStr for the above process. From these results similar thermodynamic parameters for the transfer of different nonpolar side chains and peptide groups have been determined and compared with the available data in the literature.", "contents": "Thermodynamic parameters of transfer of N-acetyl ethyl esters of different amino acids from organic solvents to water. The distribution coefficients of N-acetyl ethyl esters of glycine, diglycine, beta-alanine, alanine, valine, norvaline, leucine and norleucine between water and different organic solvents have been measured at different temperatures. Similar distribution coefficients have been measured for simple amides, urea, formamide, acetamide and N-methyl acetamide. From the distribution measurements, deltaGtr, the free energy of transfer of the solutes from organic solvents to water has been calculated. The temperature dependence of the distribution coefficient values has been utilised to determine the enthalpy of transfer, deltaHtr, and entropy of transfer deltaStr for the above process. From these results similar thermodynamic parameters for the transfer of different nonpolar side chains and peptide groups have been determined and compared with the available data in the literature."} {"id": "PMID:1279084", "title": "Cleavage of human serum transferrin with N-bromosuccinimide.", "content": "Human serum transferrin was fragmented by N-bromosuccinimide and reduction-alkylation. It was observed that there were at least two each of tryptophanyl-serine and tryptophanyl-aspartic acid, and one each of tryptophanyl-alanine and tryptophanyl-glutamic acid bonds. The size of fragments detected by polyacrylamide gel electrophoresis ranged from 8,000 to 70,000 daltons. Several of the fragments were isolated in a homogeneous form with respect to molecular weight, but were shown to be mixtures of at least five molecular species each by end group analysis.", "contents": "Cleavage of human serum transferrin with N-bromosuccinimide. Human serum transferrin was fragmented by N-bromosuccinimide and reduction-alkylation. It was observed that there were at least two each of tryptophanyl-serine and tryptophanyl-aspartic acid, and one each of tryptophanyl-alanine and tryptophanyl-glutamic acid bonds. The size of fragments detected by polyacrylamide gel electrophoresis ranged from 8,000 to 70,000 daltons. Several of the fragments were isolated in a homogeneous form with respect to molecular weight, but were shown to be mixtures of at least five molecular species each by end group analysis."} {"id": "PMID:1279085", "title": "The primary structure of muskrat pancreatic ribonuclease.", "content": "Pancreatic ribonuclease from muskrat (Ondatra zibethica) was isolated and its amino acid sequence was determined from tryptic digests of the performic acid-oxidized and the reduced and aminoethylated enzyme. The peptides have been positioned in the sequence by homology with other ribonucleases. This could be done unambiguously for all peptides except Arg-Arg (tentative position 32-33) and Ser-Arg (tentative position 75-76). The amino acid sequences of the peptides were determined by the dansyl-Edman method, with the exception of residues 23-25 and 99-102, which were positioned by homology. The enzyme differs in 38 positions from the enzyme from rat and in 31-42 positions from other mammalian pancreatic ribonucleases, while rat ribonuclease differs at 44-52 positions from the other enzymes. These data point to a common ancestry of the enzymes from muskrat and rat and an increased evolution rate of rat ribonuclease after divergence of the ancestors of both species. Muskrat ribonuclease contains no carbohydrate, although the enzyme possesses a recognition site for carbohydrate attachment in the sequence Asn-Val-Thr (62-64).", "contents": "The primary structure of muskrat pancreatic ribonuclease. Pancreatic ribonuclease from muskrat (Ondatra zibethica) was isolated and its amino acid sequence was determined from tryptic digests of the performic acid-oxidized and the reduced and aminoethylated enzyme. The peptides have been positioned in the sequence by homology with other ribonucleases. This could be done unambiguously for all peptides except Arg-Arg (tentative position 32-33) and Ser-Arg (tentative position 75-76). The amino acid sequences of the peptides were determined by the dansyl-Edman method, with the exception of residues 23-25 and 99-102, which were positioned by homology. The enzyme differs in 38 positions from the enzyme from rat and in 31-42 positions from other mammalian pancreatic ribonucleases, while rat ribonuclease differs at 44-52 positions from the other enzymes. These data point to a common ancestry of the enzymes from muskrat and rat and an increased evolution rate of rat ribonuclease after divergence of the ancestors of both species. Muskrat ribonuclease contains no carbohydrate, although the enzyme possesses a recognition site for carbohydrate attachment in the sequence Asn-Val-Thr (62-64)."} {"id": "PMID:1279086", "title": "Proton magnetic relaxation dispersion in human fluoromethaemoglobin solutions.", "content": "The solvent proton spin-lattice relaxation time of high spin Fe3+ (S=5/2) human A fluoromethaemoglobin aqueous solutions was measured at 14 Larmor frequencies in the range from 2.2 to 96 MHz. The observed paramagnetic relaxation rates are analysed in terms of the Solomon-Bloembergen theory, with the g-tensor value of 2 based on the consideration of the protein tertiary structure. From the H2O (pH 6) haemoprotein solution relaxation data, tau(c) =(9.3+/-0.3) X 10(-10) sec. If the total relaxation rates are corrected for the \"outer-sphere\" paramagnetic contribution, tau(c)=(6.5+/-0.4) X 10(-10) sec. The latter correction is obtained from the p.m.r. of the non-exchangeable aliphatic protons of C2H4(OD)2 added to the D2O-solution of fluoromethaemoglobin. Assuming that single proton transfer is taking place through the protein channel along the axis normal to the haem (g=2), the protein \"binding\" site is at a distance of 3.93 to 3.98 A from the haem Fe3+ ion.", "contents": "Proton magnetic relaxation dispersion in human fluoromethaemoglobin solutions. The solvent proton spin-lattice relaxation time of high spin Fe3+ (S=5/2) human A fluoromethaemoglobin aqueous solutions was measured at 14 Larmor frequencies in the range from 2.2 to 96 MHz. The observed paramagnetic relaxation rates are analysed in terms of the Solomon-Bloembergen theory, with the g-tensor value of 2 based on the consideration of the protein tertiary structure. From the H2O (pH 6) haemoprotein solution relaxation data, tau(c) =(9.3+/-0.3) X 10(-10) sec. If the total relaxation rates are corrected for the \"outer-sphere\" paramagnetic contribution, tau(c)=(6.5+/-0.4) X 10(-10) sec. The latter correction is obtained from the p.m.r. of the non-exchangeable aliphatic protons of C2H4(OD)2 added to the D2O-solution of fluoromethaemoglobin. Assuming that single proton transfer is taking place through the protein channel along the axis normal to the haem (g=2), the protein \"binding\" site is at a distance of 3.93 to 3.98 A from the haem Fe3+ ion."} {"id": "PMID:1279087", "title": "Silver-enhanced radial immunodiffusion assay of plasma apolipoproteins.", "content": "Silver-staining of immunoprecipitates extends the sensitivity of the radial immunodiffusion assay by tenfold. This modification permits the quantification of apolipoproteins A-I, A-II, C, and E at levels of 0.2-1.0 mg/dl in plasma samples at a sensitivity threshold of 10 ng. The silver-enhanced radial immunodiffusion method is readily adapted from the standard method, simple and inexpensive to perform, and does not require costly instrumentation. These advantages make the modified RID assay an attractive alternative to other forms of immunoassay.", "contents": "Silver-enhanced radial immunodiffusion assay of plasma apolipoproteins. Silver-staining of immunoprecipitates extends the sensitivity of the radial immunodiffusion assay by tenfold. This modification permits the quantification of apolipoproteins A-I, A-II, C, and E at levels of 0.2-1.0 mg/dl in plasma samples at a sensitivity threshold of 10 ng. The silver-enhanced radial immunodiffusion method is readily adapted from the standard method, simple and inexpensive to perform, and does not require costly instrumentation. These advantages make the modified RID assay an attractive alternative to other forms of immunoassay."} {"id": "PMID:1279088", "title": "Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein-receptor interaction.", "content": "We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with beta-galactosidase-apoB fusion proteins spanning different areas of the apoB-100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor.", "contents": "Monoclonal antibodies to human low density lipoprotein identify distinct areas on apolipoprotein B-100 relevant to the low density lipoprotein-receptor interaction. We have characterized the epitopes for ten murine monoclonal antibodies (Mabs) to human low density lipoprotein (LDL) and studied their ability to interfere with the LDL-receptor interaction. The epitopes for the antibodies were defined by using the following approaches: 1) interaction with apoB-48; 2) interaction with apoB-100 thrombolytic fragments; and 3) interaction with beta-galactosidase-apoB fusion proteins spanning different areas of the apoB-100 sequence. The results obtained are consistent with the following map of epitopes: Mab 6E, amino acids (aa) 1-1297, Mabs 5A and 6B, aa 1480-1693, Mabs 2A, 7A, 3B, and 4B, aa 2152-2377, Mabs 8A and 9A, aa 2657-3248 and 3H, aa 4082-4306. Four Mabs (2A, 5A, 7A, and 9A) whose epitopes are located in three different areas of apoB, dramatically reduced (up to 95%) the LDL-receptor interaction on cultured human fibroblasts; Fab fragments were as effective as the whole antibodies. Mab 3H, on the other hand, increased LDL binding up to threefold. These findings are consistent with the hypothesis that several areas of apoB-100 are involved independently or in concert in modulating the apoprotein B conformation required for interaction with the LDL receptor."} {"id": "PMID:1279089", "title": "Human lipoprotein lipase: relationship of activity, heparin affinity, and conformation as studied with monoclonal antibodies.", "content": "The objective of this study was to investigate how a conformational change in lipoprotein lipase (LPL) affects its molecular functions. Monoclonal antibodies (MAbs) were raised against purified bovine milk lipoprotein lipase. MAb 5D2 bound to human and bovine LPL both before and after denaturation of LPL. MAb 5F9 also recognized LPL from both species, but only after denaturation of the antigen, suggesting that a conformational change led to exposure of a previously hidden epitope. The MAbs were used in two sandwich enzyme-linked immunosorbent assays (ELISAs). One ELISA used the same MAb (5D2) to coat the plate and detect the bound antigen. This ELISA thus required the same epitope to be present in duplicate for detection (as would be the case with a dimeric antigen). The second ELISA used MAb 5F9 to coat the plate and MAb 5D2 to detect the antigen. This ELISA detected LPL only after it had been denatured. By measuring the same sample before and after denaturation with guanidine hydrochloride (GuHCl) in the 5F9 ELISA, and subtracting one from the other, a measure of native LPL was obtained. In inactivation experiments using human LPL, activity and the measure of LPL mass obtained in the 5D2 ELISA decreased and were related inversely to the measured mass obtained in the 5F9 ELISA which increased, indicating that loss of activity is closely linked to dimer dissociation and loss of native conformation. The effect of conformation and dimeric structure on LPL-heparin interaction was studied by heparin-Sepharose chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Human lipoprotein lipase: relationship of activity, heparin affinity, and conformation as studied with monoclonal antibodies. The objective of this study was to investigate how a conformational change in lipoprotein lipase (LPL) affects its molecular functions. Monoclonal antibodies (MAbs) were raised against purified bovine milk lipoprotein lipase. MAb 5D2 bound to human and bovine LPL both before and after denaturation of LPL. MAb 5F9 also recognized LPL from both species, but only after denaturation of the antigen, suggesting that a conformational change led to exposure of a previously hidden epitope. The MAbs were used in two sandwich enzyme-linked immunosorbent assays (ELISAs). One ELISA used the same MAb (5D2) to coat the plate and detect the bound antigen. This ELISA thus required the same epitope to be present in duplicate for detection (as would be the case with a dimeric antigen). The second ELISA used MAb 5F9 to coat the plate and MAb 5D2 to detect the antigen. This ELISA detected LPL only after it had been denatured. By measuring the same sample before and after denaturation with guanidine hydrochloride (GuHCl) in the 5F9 ELISA, and subtracting one from the other, a measure of native LPL was obtained. In inactivation experiments using human LPL, activity and the measure of LPL mass obtained in the 5D2 ELISA decreased and were related inversely to the measured mass obtained in the 5F9 ELISA which increased, indicating that loss of activity is closely linked to dimer dissociation and loss of native conformation. The effect of conformation and dimeric structure on LPL-heparin interaction was studied by heparin-Sepharose chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279090", "title": "The induction of specific proteases for insulin-like growth factor-binding proteins following major heart surgery.", "content": "Insulin-like growth factors (IGF-I and IGF-II) circulate bound to specific high-affinity binding proteins (IGFBPs). Recent evidence has shown that in pregnancy and severe illness, specific proteases modify these binding proteins, reducing their affinity for IGFs. We have studied 12 patients, undergoing elective coronary artery vein-bypass graft surgery, for the appearance of these proteases and have demonstrated the induction of two independent, heat-labile, cation-dependent proteases. Proteolytic activity directed against IGFBP-3 was detected in all patients between 24 h and 5 days after surgery; the second IGFBP-4 specific protease was active 1 h after sternotomy. The total IGF-I levels were found to decrease following surgery, with the IGF-I distribution in the plasma being radically altered from that seen prior to the operation. One day after the operation the majority of the IGF-I, instead of being bound in the relatively inert 150 kDa complex, was associated with the smaller binding proteins which are more readily accessible to the tissues. These findings are in contrast to pregnancy where, despite similar proteases, the majority of the IGF-I remains in the 150 kDa complex. The alteration seen in IGF-I distribution after surgery did not appear to be a direct result of the IGFBP-3 proteolytic activity or an effect of the addition of heparin to the circulation. The potential increase in bioavailability of IGFs caused by the alteration in carrier protein may play a pivotal role in countering the catabolic state induced by surgery.", "contents": "The induction of specific proteases for insulin-like growth factor-binding proteins following major heart surgery. Insulin-like growth factors (IGF-I and IGF-II) circulate bound to specific high-affinity binding proteins (IGFBPs). Recent evidence has shown that in pregnancy and severe illness, specific proteases modify these binding proteins, reducing their affinity for IGFs. We have studied 12 patients, undergoing elective coronary artery vein-bypass graft surgery, for the appearance of these proteases and have demonstrated the induction of two independent, heat-labile, cation-dependent proteases. Proteolytic activity directed against IGFBP-3 was detected in all patients between 24 h and 5 days after surgery; the second IGFBP-4 specific protease was active 1 h after sternotomy. The total IGF-I levels were found to decrease following surgery, with the IGF-I distribution in the plasma being radically altered from that seen prior to the operation. One day after the operation the majority of the IGF-I, instead of being bound in the relatively inert 150 kDa complex, was associated with the smaller binding proteins which are more readily accessible to the tissues. These findings are in contrast to pregnancy where, despite similar proteases, the majority of the IGF-I remains in the 150 kDa complex. The alteration seen in IGF-I distribution after surgery did not appear to be a direct result of the IGFBP-3 proteolytic activity or an effect of the addition of heparin to the circulation. The potential increase in bioavailability of IGFs caused by the alteration in carrier protein may play a pivotal role in countering the catabolic state induced by surgery."} {"id": "PMID:1279091", "title": "Comparison of specific immunoassays for detection of the beta-core human chorionic gonadotrophin fragment in body fluids.", "content": "We have validated two new methods, one radioimmunoassay (RIA) and one immunoradiometric assay (IRMA), for the detection of beta-core hCG fragment (beta C-hCG) in body fluids. In addition, we have compared their performance with two other assays designed for beta C-hCG quantification. The RIA uses a rabbit polyclonal antibody raised against pure beta C-hCG which has a high affinity constant, is sensitive to 5 pmol/l, and has significant cross-reaction only with the free beta LH subunit. The IRMA, designed in a liquid phase, uses the same polyclonal antibody associated with a 125I-labelled mouse monoclonal antibody (32H2) raised against beta hCG, is sensitive to 1.5 pmol/l, and does not cross-react significantly with any related glycoprotein. Comparison between these two assays and two others previously published was made by measuring beta C-hCG in urine from healthy pregnant women (n = 47) and gave correlation coefficients higher than r = 0.960 with any combination. Analysis of beta C-hCG in urine of non-pregnant subjects (n = 238) showed measurable beta C-hCG in 8.8% (levels ranged from 5 to 34 pmol/l) with the IRMA and 88.3% with the RIA (n = 30; ranging from 28.4 to 228 pmol/l) (P = 0.05). We concluded that, despite different affinities of the antibody involved and different cross-reactivities with related glycoproteins, the four assays we examined may be equally employed to detect beta C-hCG in pregnancy urine. However, the IRMA appears to be more appropriate for beta C-hCG analysis in non-pregnant individuals, specifically in postmenopausal women because of the high cross-reactivity of the RIA with free beta LH or beta fragments of other glycoproteins. These studies have significance for our understanding of the physiology of beta C-hCG in cancer, pregnancy and after the menopause.", "contents": "Comparison of specific immunoassays for detection of the beta-core human chorionic gonadotrophin fragment in body fluids. We have validated two new methods, one radioimmunoassay (RIA) and one immunoradiometric assay (IRMA), for the detection of beta-core hCG fragment (beta C-hCG) in body fluids. In addition, we have compared their performance with two other assays designed for beta C-hCG quantification. The RIA uses a rabbit polyclonal antibody raised against pure beta C-hCG which has a high affinity constant, is sensitive to 5 pmol/l, and has significant cross-reaction only with the free beta LH subunit. The IRMA, designed in a liquid phase, uses the same polyclonal antibody associated with a 125I-labelled mouse monoclonal antibody (32H2) raised against beta hCG, is sensitive to 1.5 pmol/l, and does not cross-react significantly with any related glycoprotein. Comparison between these two assays and two others previously published was made by measuring beta C-hCG in urine from healthy pregnant women (n = 47) and gave correlation coefficients higher than r = 0.960 with any combination. Analysis of beta C-hCG in urine of non-pregnant subjects (n = 238) showed measurable beta C-hCG in 8.8% (levels ranged from 5 to 34 pmol/l) with the IRMA and 88.3% with the RIA (n = 30; ranging from 28.4 to 228 pmol/l) (P = 0.05). We concluded that, despite different affinities of the antibody involved and different cross-reactivities with related glycoproteins, the four assays we examined may be equally employed to detect beta C-hCG in pregnancy urine. However, the IRMA appears to be more appropriate for beta C-hCG analysis in non-pregnant individuals, specifically in postmenopausal women because of the high cross-reactivity of the RIA with free beta LH or beta fragments of other glycoproteins. These studies have significance for our understanding of the physiology of beta C-hCG in cancer, pregnancy and after the menopause."} {"id": "PMID:1279092", "title": "Distribution of the beta-core human chorionic gonadotrophin fragment in human body fluids.", "content": "The origins of a fragment of the human chorionic gonadotrophin (hCG) molecule, beta-core (beta C-hCG) were studied by analysis of beta C-hCG concentrations in biological fluids. In addition, the ability of the placenta to produce the fragment and the metabolism of hCG to beta C-hCG by human granulosa cells was determined in tissue culture. Finally the conversion of exogenous hCG to beta C-hCG was studied in vivo. The fragment was present in pregnancy urine as well as that from premenopausal and postmenopausal subjects. The highest concentrations were found in pregnant women. Ratios of beta C-hCG to intact hCG were higher in pregnancy urine when radioimmunoassay (RIA) was used compared with immunoradiometric assay (IRMA) (0.67 and 0.37 respectively). Concentrations of beta C-hCG were higher in postmenopausal urine than in premenopausal specimens. A significant amount of a high molecular weight beta C-hCG immunoreactive material was found in serum samples after size separation, and the molar ratio of beta C-hCG/hCG was estimated as 0.019. Amniotic fluid also contained small quantities of two forms of immunoreactive beta C-hCG and the ratio of 0.01 for authentic beta C-hCG/hCG increased to 0.026 when the high molecular weight form was considered. Cultured trophoblastic tissue released material with beta C-hCG immunoreactivity in the medium and chromatographic separation revealed that the majority of this material was of higher molecular weight compared with the authentic beta C-hCG form. beta C-hCG was the principal glycoprotein found in follicular fluid after hyperstimulated folliculogenesis and intramuscular injection of 5000 IU hCG. We also demonstrated that 26% of follicular fluid samples (n = 50) were positive for beta C-hCG; levels ranged from 5.2 to 23.0 pmol/l (13.1 +/- 5.7); S.D.) when a specific IRMA was used. The RIA could detect beta C-hCG in 48 samples (96%), levels ranging from 7.0 to 28.5 pmol/l (19.4 +/- 5.2). Moreover, granulosa cells cultured in the presence of hCG were able to degrade the intact molecule to both high molecular weight and authentic immunoreactive forms of beta C-hCG. After gel filtration, material of molecular weight over a wide range and immunoreactive for beta C-hCG was present in human seminal plasma. Assaying 74 samples of this fluid by IRMA, beta C-hCG was detected in 42 (56.7%), levels ranging between 5.5 and 59.5 pmol/l (24.9 +/- 15.2).(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Distribution of the beta-core human chorionic gonadotrophin fragment in human body fluids. The origins of a fragment of the human chorionic gonadotrophin (hCG) molecule, beta-core (beta C-hCG) were studied by analysis of beta C-hCG concentrations in biological fluids. In addition, the ability of the placenta to produce the fragment and the metabolism of hCG to beta C-hCG by human granulosa cells was determined in tissue culture. Finally the conversion of exogenous hCG to beta C-hCG was studied in vivo. The fragment was present in pregnancy urine as well as that from premenopausal and postmenopausal subjects. The highest concentrations were found in pregnant women. Ratios of beta C-hCG to intact hCG were higher in pregnancy urine when radioimmunoassay (RIA) was used compared with immunoradiometric assay (IRMA) (0.67 and 0.37 respectively). Concentrations of beta C-hCG were higher in postmenopausal urine than in premenopausal specimens. A significant amount of a high molecular weight beta C-hCG immunoreactive material was found in serum samples after size separation, and the molar ratio of beta C-hCG/hCG was estimated as 0.019. Amniotic fluid also contained small quantities of two forms of immunoreactive beta C-hCG and the ratio of 0.01 for authentic beta C-hCG/hCG increased to 0.026 when the high molecular weight form was considered. Cultured trophoblastic tissue released material with beta C-hCG immunoreactivity in the medium and chromatographic separation revealed that the majority of this material was of higher molecular weight compared with the authentic beta C-hCG form. beta C-hCG was the principal glycoprotein found in follicular fluid after hyperstimulated folliculogenesis and intramuscular injection of 5000 IU hCG. We also demonstrated that 26% of follicular fluid samples (n = 50) were positive for beta C-hCG; levels ranged from 5.2 to 23.0 pmol/l (13.1 +/- 5.7); S.D.) when a specific IRMA was used. The RIA could detect beta C-hCG in 48 samples (96%), levels ranging from 7.0 to 28.5 pmol/l (19.4 +/- 5.2). Moreover, granulosa cells cultured in the presence of hCG were able to degrade the intact molecule to both high molecular weight and authentic immunoreactive forms of beta C-hCG. After gel filtration, material of molecular weight over a wide range and immunoreactive for beta C-hCG was present in human seminal plasma. Assaying 74 samples of this fluid by IRMA, beta C-hCG was detected in 42 (56.7%), levels ranging between 5.5 and 59.5 pmol/l (24.9 +/- 15.2).(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279093", "title": "Delayed root canal therapy: an analysis of treatment over time.", "content": "A retrospective study of 898 teeth receiving root canal therapy was performed to document the sequelae of delayed completion of root canal treatment. Teeth were categorized into a prompt treatment group and a delayed treatment group. Comparisons of prompt and delayed treatment groups were made with regard to preoperative pain, interappointment emergencies, postobturation pain, and final treatment. Findings from this study show that a palliative endodontic procedure is an extremely effective treatment. However, 56% of teeth with incomplete root canal therapy eventually were extracted compared with 2 to 3% for the root canal filling treatment groups. By emphasizing the potential loss of the tooth rather than the potential of interappointment emergencies, the clinician may be more effective in achieving compliance among patients receiving delayed treatment.", "contents": "Delayed root canal therapy: an analysis of treatment over time. A retrospective study of 898 teeth receiving root canal therapy was performed to document the sequelae of delayed completion of root canal treatment. Teeth were categorized into a prompt treatment group and a delayed treatment group. Comparisons of prompt and delayed treatment groups were made with regard to preoperative pain, interappointment emergencies, postobturation pain, and final treatment. Findings from this study show that a palliative endodontic procedure is an extremely effective treatment. However, 56% of teeth with incomplete root canal therapy eventually were extracted compared with 2 to 3% for the root canal filling treatment groups. By emphasizing the potential loss of the tooth rather than the potential of interappointment emergencies, the clinician may be more effective in achieving compliance among patients receiving delayed treatment."} {"id": "PMID:1279094", "title": "Monoclonal antibody ST1 identifies an antigen that is abundant in the axolotl and newt limb stump but is absent from the undifferentiated regenerate.", "content": "Monoclonal antibodies (mAb) utilized in regeneration studies to date identify antigens that are up-regulated in the blastema. We obtained a monoclonal antibody, designated ST1 (Stump 1), that is reactive to an extracellular matrix (ECM) antigen exhibiting the opposite distribution; ST1 is an abundant antigen of the limb stump soft tissues but is absent from within the blastema. The border between abundance and absence of mAb ST1 reactivity was sharp and extended as a concavity into the stump. This distinct dichotomy led to further studies relevant to understanding how this extracellular matrix antigen is modulated during regeneration. mAb ST1 reactivity decreased in the internal tissues at the distal end of the limb prior to blastema formation and remained absent until the onset of differentiation. The initial decrease in mAb ST1 reactivity was dependent on the combined effects of injury and the wound epithelium but was nerve independent. At blastema stages of regeneration, the distribution of tenascin, ascertained by mAb MT1 reactivity, closely matched the area without reactivity to mAb ST1. The spatial and temporal distribution of the ST1 antigen in unamputated limbs and during regeneration did not correspond to any previously described ECM component.", "contents": "Monoclonal antibody ST1 identifies an antigen that is abundant in the axolotl and newt limb stump but is absent from the undifferentiated regenerate. Monoclonal antibodies (mAb) utilized in regeneration studies to date identify antigens that are up-regulated in the blastema. We obtained a monoclonal antibody, designated ST1 (Stump 1), that is reactive to an extracellular matrix (ECM) antigen exhibiting the opposite distribution; ST1 is an abundant antigen of the limb stump soft tissues but is absent from within the blastema. The border between abundance and absence of mAb ST1 reactivity was sharp and extended as a concavity into the stump. This distinct dichotomy led to further studies relevant to understanding how this extracellular matrix antigen is modulated during regeneration. mAb ST1 reactivity decreased in the internal tissues at the distal end of the limb prior to blastema formation and remained absent until the onset of differentiation. The initial decrease in mAb ST1 reactivity was dependent on the combined effects of injury and the wound epithelium but was nerve independent. At blastema stages of regeneration, the distribution of tenascin, ascertained by mAb MT1 reactivity, closely matched the area without reactivity to mAb ST1. The spatial and temporal distribution of the ST1 antigen in unamputated limbs and during regeneration did not correspond to any previously described ECM component."} {"id": "PMID:1279095", "title": "Divalent cation conduction in the ryanodine receptor channel of sheep cardiac muscle sarcoplasmic reticulum.", "content": "The conduction properties of the alkaline earth divalent cations were determined in the purified sheep cardiac sarcoplasmic reticulum ryanodine receptor channel after reconstitution into planar phospholipid bilayers. Under bi-ionic conditions there was little difference in permeability among Ba2+, Ca2+, Sr2+, and Mg2+. However, there was a significant difference between the divalent cations and K+, with the divalent cations between 5.8- and 6.7-fold more permeant. Single-channel conductances were determined under symmetrical ionic conditions with 210 mM Ba2+ and Sr2+ and from the single-channel current-voltage relationship under bi-ionic conditions with 210 mM divalent cations and 210 mM K+. Single-channel conductance ranged from 202 pS for Ba2+ to 89 pS for Mg2+ and fell in the sequence Ba2+ greater than Sr2+ greater than Ca2+ greater than Mg2+. Near-maximal single-channel conductance is observed at concentrations as low as 2 mM Ba2+. Single-channel conductance and current measurements in mixtures of Ba(2+)-Mg2+ and Ba(2+)-Ca2+ reveal no anomalous behavior as the mole fraction of the ions is varied. The Ca(2+)-K+ reversal potential determined under bi-ionic conditions was independent of the absolute value of the ion concentrations. The data are compatible with the ryanodine receptor channel acting as a high conductance channel displaying moderate discrimination between divalent and monovalent cations. The channel behaves as though ion translocation occurs in single file with at most one ion able to occupy the conduction pathway at a time.", "contents": "Divalent cation conduction in the ryanodine receptor channel of sheep cardiac muscle sarcoplasmic reticulum. The conduction properties of the alkaline earth divalent cations were determined in the purified sheep cardiac sarcoplasmic reticulum ryanodine receptor channel after reconstitution into planar phospholipid bilayers. Under bi-ionic conditions there was little difference in permeability among Ba2+, Ca2+, Sr2+, and Mg2+. However, there was a significant difference between the divalent cations and K+, with the divalent cations between 5.8- and 6.7-fold more permeant. Single-channel conductances were determined under symmetrical ionic conditions with 210 mM Ba2+ and Sr2+ and from the single-channel current-voltage relationship under bi-ionic conditions with 210 mM divalent cations and 210 mM K+. Single-channel conductance ranged from 202 pS for Ba2+ to 89 pS for Mg2+ and fell in the sequence Ba2+ greater than Sr2+ greater than Ca2+ greater than Mg2+. Near-maximal single-channel conductance is observed at concentrations as low as 2 mM Ba2+. Single-channel conductance and current measurements in mixtures of Ba(2+)-Mg2+ and Ba(2+)-Ca2+ reveal no anomalous behavior as the mole fraction of the ions is varied. The Ca(2+)-K+ reversal potential determined under bi-ionic conditions was independent of the absolute value of the ion concentrations. The data are compatible with the ryanodine receptor channel acting as a high conductance channel displaying moderate discrimination between divalent and monovalent cations. The channel behaves as though ion translocation occurs in single file with at most one ion able to occupy the conduction pathway at a time."} {"id": "PMID:1279096", "title": "A model for ionic conduction in the ryanodine receptor channel of sheep cardiac muscle sarcoplasmic reticulum.", "content": "A model is developed for ionic conduction in the sheep cardiac sarcoplasmic reticulum ryanodine receptor channel based on Eyring rate theory. A simple scheme is proposed founded on single-ion occupancy and an energy profile with four barriers and three binding sites. The model is able to quantitatively predict a large number of conduction properties of the purified and native receptor with monovalent and divalent cations as permeant species. It suggests that discrimination between divalent and monovalent cations is due to a high affinity central binding site and a process that favors the passage of divalent cations between binding sites. Furthermore, differences in conductance among the group Ia cations and among the alkaline earths are largely explained by differing affinity at this putative central binding site.", "contents": "A model for ionic conduction in the ryanodine receptor channel of sheep cardiac muscle sarcoplasmic reticulum. A model is developed for ionic conduction in the sheep cardiac sarcoplasmic reticulum ryanodine receptor channel based on Eyring rate theory. A simple scheme is proposed founded on single-ion occupancy and an energy profile with four barriers and three binding sites. The model is able to quantitatively predict a large number of conduction properties of the purified and native receptor with monovalent and divalent cations as permeant species. It suggests that discrimination between divalent and monovalent cations is due to a high affinity central binding site and a process that favors the passage of divalent cations between binding sites. Furthermore, differences in conductance among the group Ia cations and among the alkaline earths are largely explained by differing affinity at this putative central binding site."} {"id": "PMID:1279097", "title": "Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current.", "content": "The properties of the low threshold Ca current (ICaT) in bullfrog (Rana catesbeiana) isolated atrial cardiomyocytes were studied using the whole-cell recording patch-clamp technique and compared with those of the high threshold Ca current (ICaL). In 91% of atrial cells we observed both ICaT and ICaL when collagenase and trypsin were used to dissociate the cells. But when pronase was used, only 30% of the cells exhibited ICaT. ICaT was never found in ventricular cells. ICaT could be investigated more easily when ICaL was inhibited by Cd ions (50 microM). Its kinetics were unchanged by substituting Ba for Ca, or in the presence of high concentrations of Ba. Both ICaT and ICaL exhibited reduced inactivation after high depolarizing prepulses. ICaT was found to be sensitive to dihydropyridines: 1 microM nifedipine decreased this current while 1 microM BAY K 8644 increased it; this occurred without significant variations in the steady-state inactivation curve. ICaT was more sensitive than ICaL to alpha 1-adrenergic and P2-purinergic stimulations, while ICaL was more sensitive to beta-adrenergic stimulation. Isoproterenol was still able to increase ICaT in the presence of high intracellular cAMP. Both currents were increased by 1 microM ouabain (although ICaL only transiently) and decreased by 10 microM ouabain. It is concluded that the two types of Ca channels can be observed in bullfrog atrial cells and that they are specifically altered by pharmacological agents and neuromediators. This may have implications for cardiac behavior.", "contents": "Properties of the low threshold Ca current in single frog atrial cardiomyocytes. A comparison with the high threshold Ca current. The properties of the low threshold Ca current (ICaT) in bullfrog (Rana catesbeiana) isolated atrial cardiomyocytes were studied using the whole-cell recording patch-clamp technique and compared with those of the high threshold Ca current (ICaL). In 91% of atrial cells we observed both ICaT and ICaL when collagenase and trypsin were used to dissociate the cells. But when pronase was used, only 30% of the cells exhibited ICaT. ICaT was never found in ventricular cells. ICaT could be investigated more easily when ICaL was inhibited by Cd ions (50 microM). Its kinetics were unchanged by substituting Ba for Ca, or in the presence of high concentrations of Ba. Both ICaT and ICaL exhibited reduced inactivation after high depolarizing prepulses. ICaT was found to be sensitive to dihydropyridines: 1 microM nifedipine decreased this current while 1 microM BAY K 8644 increased it; this occurred without significant variations in the steady-state inactivation curve. ICaT was more sensitive than ICaL to alpha 1-adrenergic and P2-purinergic stimulations, while ICaL was more sensitive to beta-adrenergic stimulation. Isoproterenol was still able to increase ICaT in the presence of high intracellular cAMP. Both currents were increased by 1 microM ouabain (although ICaL only transiently) and decreased by 10 microM ouabain. It is concluded that the two types of Ca channels can be observed in bullfrog atrial cells and that they are specifically altered by pharmacological agents and neuromediators. This may have implications for cardiac behavior."} {"id": "PMID:1279098", "title": "A viroid from Nematanthus wettsteinii plants closely related to the Columnea latent viroid.", "content": "A viroid was isolated from symptomless Nematanthus wettsteinii plants using the return-PAGE method for analysis of low M(r) nucleic acids. The RNA was transmitted to tomato, three cultivars of potato, and Scopolia sinensis plants by mechanical inoculation or by grafting. Infected solanaceous plants developed symptoms similar to those caused by potato spindle tuber viroid (PSTVd). The Nematanthus viroid consists of 372 nucleotides, 214 G+C, 158 A+U, with a G+C/A+U ratio of 1.35. One of seven cDNA clones showed a sequence heterogeneity (G to A) at position 73. The most stable secondary structure of this viroid has 78 G:C, 37 A:U and 11 G:U base pairs with a minimum free energy of -456.9 kJ. The viroid is closely related to the 370 nucleotide Columnea latent viroid. The Nematanthus viroid possesses regions of 100% sequence identity with six viroids belonging to the PSTVd and apple scar skin viroid groups. The viroid also replicated in tomato plants when mixed with PSTVd. Tomato plants were cross-protected against PSTVd when preinfected with the viroid from N. wettsteinii.", "contents": "A viroid from Nematanthus wettsteinii plants closely related to the Columnea latent viroid. A viroid was isolated from symptomless Nematanthus wettsteinii plants using the return-PAGE method for analysis of low M(r) nucleic acids. The RNA was transmitted to tomato, three cultivars of potato, and Scopolia sinensis plants by mechanical inoculation or by grafting. Infected solanaceous plants developed symptoms similar to those caused by potato spindle tuber viroid (PSTVd). The Nematanthus viroid consists of 372 nucleotides, 214 G+C, 158 A+U, with a G+C/A+U ratio of 1.35. One of seven cDNA clones showed a sequence heterogeneity (G to A) at position 73. The most stable secondary structure of this viroid has 78 G:C, 37 A:U and 11 G:U base pairs with a minimum free energy of -456.9 kJ. The viroid is closely related to the 370 nucleotide Columnea latent viroid. The Nematanthus viroid possesses regions of 100% sequence identity with six viroids belonging to the PSTVd and apple scar skin viroid groups. The viroid also replicated in tomato plants when mixed with PSTVd. Tomato plants were cross-protected against PSTVd when preinfected with the viroid from N. wettsteinii."} {"id": "PMID:1279099", "title": "Widely separated sequence elements within cucumber mosaic virus satellites contribute to their ability to induce lethal tomato necrosis.", "content": "To determine the structural requirements for cucumber mosaic virus (CMV) satellites to elicit lethal tomato necrosis, three satellite variants D, S and Y were used in the construction and cloning of chimeric cDNAs. D and S are necrogenic and non-necrogenic 'prototype' variants, respectively, and Y possesses the 3' conserved necrosis-determining region but does not cause lethal tomato necrosis. Its 5' half harbours an insertion/deletion region that results in a molecule about 30 nucleotides longer than other variants. Tomato bio-assays were conducted with RNA transcripts of all six chimeric combinations of the 5' and 3' halves of the three satellite variants divided by a common restriction site, as well as with a mutated chimera. None of the chimeras containing the 5' half of Y induced lethal necrosis in tomato even when their 3' halves were that of the D variant with the conserved necrogenic element. Chimeras with the 3' half of Y elicited only partial or restricted necrosis which was much less severe than that induced by prototype variant D, and often was not lethal. Site-directed mutation of a single nucleotide in proximity to the necrogenic element of such a chimera containing the 3' half of Y restored much lethal necrogenicity. The results revealed the presence of structural elements in CMV satellite variant Y that modulate or even suppress the expression of the 3' conserved necrosis-determining element. They indicate that in CMV satellites widely separated sequence elements constituting a three-dimensional requirement are responsible for eliciting lethal necrosis in tomato.", "contents": "Widely separated sequence elements within cucumber mosaic virus satellites contribute to their ability to induce lethal tomato necrosis. To determine the structural requirements for cucumber mosaic virus (CMV) satellites to elicit lethal tomato necrosis, three satellite variants D, S and Y were used in the construction and cloning of chimeric cDNAs. D and S are necrogenic and non-necrogenic 'prototype' variants, respectively, and Y possesses the 3' conserved necrosis-determining region but does not cause lethal tomato necrosis. Its 5' half harbours an insertion/deletion region that results in a molecule about 30 nucleotides longer than other variants. Tomato bio-assays were conducted with RNA transcripts of all six chimeric combinations of the 5' and 3' halves of the three satellite variants divided by a common restriction site, as well as with a mutated chimera. None of the chimeras containing the 5' half of Y induced lethal necrosis in tomato even when their 3' halves were that of the D variant with the conserved necrogenic element. Chimeras with the 3' half of Y elicited only partial or restricted necrosis which was much less severe than that induced by prototype variant D, and often was not lethal. Site-directed mutation of a single nucleotide in proximity to the necrogenic element of such a chimera containing the 3' half of Y restored much lethal necrogenicity. The results revealed the presence of structural elements in CMV satellite variant Y that modulate or even suppress the expression of the 3' conserved necrosis-determining element. They indicate that in CMV satellites widely separated sequence elements constituting a three-dimensional requirement are responsible for eliciting lethal necrosis in tomato."} {"id": "PMID:1279100", "title": "Identification of viral structural polypeptides of Thogoto virus (a tick-borne orthomyxo-like virus) and functions associated with the glycoprotein.", "content": "Thogoto (THO) virus is a tick-borne virus which shares morphological and genetic features with members of the Orthomyxoviridae family although the viral glycoprotein appears to be related to gp64 of baculoviruses. Characterization of THO virus was undertaken to clarify its taxonomic position. Purified virus preparations contained at least six virus-encoded polypeptides with apparent M(r) values ranging from 29K to 92K. A 75K polypeptide was identified as an envelope-associated glycoprotein by Triton X-100 and salt dissociation studies, and by proteolytic degradation of the exposed proteins of the virion. By the same criteria, the nucleoprotein and the matrix protein were identified as the 52K and 29K polypeptides, respectively. Immunofluorescence studies using monoclonal antibodies (MAbs) located the glycoprotein on the external cell membrane and the nucleoprotein in the nucleus of infected cells indicating that virus replication involved a nuclear phase. In addition, the virus displayed haemagglutination and haemolytic activities with an optimum at pH 6. These activities are functions of the viral glycoprotein since they were inhibited by anti-glycoprotein MAbs. The data reported here support the notion that THO virus is a member of the Orthomyxoviridae family but that it should be classified in a group distinct from the other influenza viruses.", "contents": "Identification of viral structural polypeptides of Thogoto virus (a tick-borne orthomyxo-like virus) and functions associated with the glycoprotein. Thogoto (THO) virus is a tick-borne virus which shares morphological and genetic features with members of the Orthomyxoviridae family although the viral glycoprotein appears to be related to gp64 of baculoviruses. Characterization of THO virus was undertaken to clarify its taxonomic position. Purified virus preparations contained at least six virus-encoded polypeptides with apparent M(r) values ranging from 29K to 92K. A 75K polypeptide was identified as an envelope-associated glycoprotein by Triton X-100 and salt dissociation studies, and by proteolytic degradation of the exposed proteins of the virion. By the same criteria, the nucleoprotein and the matrix protein were identified as the 52K and 29K polypeptides, respectively. Immunofluorescence studies using monoclonal antibodies (MAbs) located the glycoprotein on the external cell membrane and the nucleoprotein in the nucleus of infected cells indicating that virus replication involved a nuclear phase. In addition, the virus displayed haemagglutination and haemolytic activities with an optimum at pH 6. These activities are functions of the viral glycoprotein since they were inhibited by anti-glycoprotein MAbs. The data reported here support the notion that THO virus is a member of the Orthomyxoviridae family but that it should be classified in a group distinct from the other influenza viruses."} {"id": "PMID:1279101", "title": "Analysis of splice sites in the early region of bovine polyomavirus: evidence for a unique pattern of large T mRNA splicing.", "content": "The genetic organization of the early region of bovine polyomavirus (BPyV) was studied by analysis of the splice sites used in early mRNA maturation, using reverse transcription-polymerase chain reaction and DNA sequencing techniques. When compared to other polyomaviruses, the BPyV early region appears to have an uncommon organization. In the major early mRNA molecule two small intron sequences of 71 and 77 nucleotides, separated from one another by an 80 nucleotide exon sequence, were identified. Through splicing out both introns, a mRNA molecule is generated that contains an open reading frame with the capacity to encode 619 amino acids. Comparisons with the simian virus 40 large T antigen suggested that this mRNA molecule encodes the BPyV large T antigen. Remarkably, no mRNA product encoding a protein with a size comparable to that of the small t antigens of other polyomaviruses was detected. Another transcript was observed from which only the 77 nucleotide intron sequence had been removed, thereby creating a mRNA molecule with the capacity to encode only 45 amino acids. Whether this mRNA product represents a mature transcript which is translated in BPyV-infected cells or is an intermediate in the formation of the large T mRNA molecule is not known. Analysis of BPyV-specific early mRNA products isolated from BPyV-transformed murine cells revealed only the amplification product representing the putative large T antigen transcript.", "contents": "Analysis of splice sites in the early region of bovine polyomavirus: evidence for a unique pattern of large T mRNA splicing. The genetic organization of the early region of bovine polyomavirus (BPyV) was studied by analysis of the splice sites used in early mRNA maturation, using reverse transcription-polymerase chain reaction and DNA sequencing techniques. When compared to other polyomaviruses, the BPyV early region appears to have an uncommon organization. In the major early mRNA molecule two small intron sequences of 71 and 77 nucleotides, separated from one another by an 80 nucleotide exon sequence, were identified. Through splicing out both introns, a mRNA molecule is generated that contains an open reading frame with the capacity to encode 619 amino acids. Comparisons with the simian virus 40 large T antigen suggested that this mRNA molecule encodes the BPyV large T antigen. Remarkably, no mRNA product encoding a protein with a size comparable to that of the small t antigens of other polyomaviruses was detected. Another transcript was observed from which only the 77 nucleotide intron sequence had been removed, thereby creating a mRNA molecule with the capacity to encode only 45 amino acids. Whether this mRNA product represents a mature transcript which is translated in BPyV-infected cells or is an intermediate in the formation of the large T mRNA molecule is not known. Analysis of BPyV-specific early mRNA products isolated from BPyV-transformed murine cells revealed only the amplification product representing the putative large T antigen transcript."} {"id": "PMID:1279102", "title": "Assembly of conformation-dependent neutralizing domains on glycoprotein B of human cytomegalovirus.", "content": "We analysed the antigenic properties of human cytomegalovirus (CMV) glycoprotein B (gB) by constructing a set of deletion derivatives lacking different portions of the carboxy terminus and reacting them with a panel of monoclonal antibodies with neutralizing activity. We found that two novel antigenic domains that bind neutralizing antibodies were assembled on truncated forms of gB, one in the amino-terminal half and one that spans the midregion of the molecule. Assembly of the conformation-dependent epitopes occurred independently of residues in the carboxy-terminal half of the molecule and did not depend on proteolytic cleavage of the molecule between amino acids 460 and 461. Ten antibodies recognized a derivative with 447 amino-terminal residues; their failure to recognize a derivative 411 residues long suggested that the amino acids required for assembly of these epitopes either were incorrectly folded, or had been totally or partially deleted in this derivative. Epitopes for three antibodies with complement-independent neutralizing activity were assembled when amino acids from the midregion of gB between residues 447 and 476 were present. Two other antigenic domains were formed by the addition of residues 476 to 618 and 619 to 645 from the carboxy-terminal half of gB. Our results underscore the importance of conformation in the antigenic structure and functional properties of both the amino- and carboxy-terminal portions of gB.", "contents": "Assembly of conformation-dependent neutralizing domains on glycoprotein B of human cytomegalovirus. We analysed the antigenic properties of human cytomegalovirus (CMV) glycoprotein B (gB) by constructing a set of deletion derivatives lacking different portions of the carboxy terminus and reacting them with a panel of monoclonal antibodies with neutralizing activity. We found that two novel antigenic domains that bind neutralizing antibodies were assembled on truncated forms of gB, one in the amino-terminal half and one that spans the midregion of the molecule. Assembly of the conformation-dependent epitopes occurred independently of residues in the carboxy-terminal half of the molecule and did not depend on proteolytic cleavage of the molecule between amino acids 460 and 461. Ten antibodies recognized a derivative with 447 amino-terminal residues; their failure to recognize a derivative 411 residues long suggested that the amino acids required for assembly of these epitopes either were incorrectly folded, or had been totally or partially deleted in this derivative. Epitopes for three antibodies with complement-independent neutralizing activity were assembled when amino acids from the midregion of gB between residues 447 and 476 were present. Two other antigenic domains were formed by the addition of residues 476 to 618 and 619 to 645 from the carboxy-terminal half of gB. Our results underscore the importance of conformation in the antigenic structure and functional properties of both the amino- and carboxy-terminal portions of gB."} {"id": "PMID:1279103", "title": "Cyclic AMP-mediated inhibition of vesicular stomatitis virus and herpes simplex virus replication in mouse macrophage-like cells.", "content": "In this study, we have analysed the effects of cAMP inducers on the multiplication of vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) in mouse macrophage-like cells. The addition of dibutyryl cAMP (dB-cAMP) or cholera toxin to resting peritoneal macrophages aged in vitro or P388D1 cells resulted in a 10- to 100-fold reduction of VSV yield compared to control cultures. In contrast, no cAMP-dependent inhibition was found in VSV-infected L929 cells. In macrophage-like cells, the dB-cAMP-induced antiviral state was not inhibited by antibodies to interferon (IFN)-alpha/beta and did not correlate with any increase in the intracellular levels of 2-5 oligo(A) synthetase. Dibutyryl cAMP did not inhibit virus yields in mouse macrophages infected with encephalomyocarditis virus. In P388D1 cells, the addition of dB-cAMP resulted in an approximately 10-fold inhibition of HSV-1 replication with respect to control cultures, as evaluated both by TCID50 and plaque assays on Vero cells. Dibutyryl cAMP did not affect VSV binding or entry into mouse macrophages and the cAMP-mediated anti-VSV state was significantly reduced by inhibitors of protein kinase C (i.e. staurosporine and H7). These data suggest that macrophages may acquire resistance to infection by VSV and HSV-1 after treatment with cAMP inducers. This cAMP-mediated antiviral activity does not depend on the modulation of the endogenous IFN system, suggesting that macrophages exhibit multiple resistance mechanisms (i.e. IFN-dependent and IFN-independent) to maintain their intrinsic antiviral activity.", "contents": "Cyclic AMP-mediated inhibition of vesicular stomatitis virus and herpes simplex virus replication in mouse macrophage-like cells. In this study, we have analysed the effects of cAMP inducers on the multiplication of vesicular stomatitis virus (VSV) and herpes simplex virus type 1 (HSV-1) in mouse macrophage-like cells. The addition of dibutyryl cAMP (dB-cAMP) or cholera toxin to resting peritoneal macrophages aged in vitro or P388D1 cells resulted in a 10- to 100-fold reduction of VSV yield compared to control cultures. In contrast, no cAMP-dependent inhibition was found in VSV-infected L929 cells. In macrophage-like cells, the dB-cAMP-induced antiviral state was not inhibited by antibodies to interferon (IFN)-alpha/beta and did not correlate with any increase in the intracellular levels of 2-5 oligo(A) synthetase. Dibutyryl cAMP did not inhibit virus yields in mouse macrophages infected with encephalomyocarditis virus. In P388D1 cells, the addition of dB-cAMP resulted in an approximately 10-fold inhibition of HSV-1 replication with respect to control cultures, as evaluated both by TCID50 and plaque assays on Vero cells. Dibutyryl cAMP did not affect VSV binding or entry into mouse macrophages and the cAMP-mediated anti-VSV state was significantly reduced by inhibitors of protein kinase C (i.e. staurosporine and H7). These data suggest that macrophages may acquire resistance to infection by VSV and HSV-1 after treatment with cAMP inducers. This cAMP-mediated antiviral activity does not depend on the modulation of the endogenous IFN system, suggesting that macrophages exhibit multiple resistance mechanisms (i.e. IFN-dependent and IFN-independent) to maintain their intrinsic antiviral activity."} {"id": "PMID:1279104", "title": "Human sera from varicella-zoster virus (VZV) infections cross-react with human T cell leukaemia virus type 1 (HTLV-1): common epitopes in VZV gene 22 protein and HTLV-1 p19 gag protein.", "content": "Twenty-nine of 100 sera from patients recently infected with varicella-zoster virus (VZV) were found to cross-react with human T cell leukaemia virus type 1 (HTLV-1) antigen in the particle agglutination (PA) assay using HTLV-1 antigen-coated gelatin particles. Anti-VZV IgM antibodies were shown to be responsible for this cross-reactivity. Western blot analysis revealed that PA-positive anti-VZV sera reacted with the HTLV-1 gag p19 protein in HTLV-1-infected cells and recombinant p19 protein produced in Escherichia coli. By using a truncated p19, the cross-reactive region was located to the C-terminal 17 amino acids of p19. One oligopeptide derived from the C terminus, PQIPPPYVEPT (amino acids 115 to 125), was capable of inhibiting PA, suggesting that this peptide carries the cross-reactive epitope. A homologous sequence was found in the VZV gene 22 protein by database analysis, and the oligopeptide TNIPPPLALLR (amino acids 1330 to 1340) had the ability to inhibit PA. These findings suggest that some IgM antibodies against the VZV gene 22 protein produced in the early phase of VZV infection are cross-reactive with the HTLV-1 gag p19 protein because they recognize an antigenic determinant containing an IPPP tetrapeptide.", "contents": "Human sera from varicella-zoster virus (VZV) infections cross-react with human T cell leukaemia virus type 1 (HTLV-1): common epitopes in VZV gene 22 protein and HTLV-1 p19 gag protein. Twenty-nine of 100 sera from patients recently infected with varicella-zoster virus (VZV) were found to cross-react with human T cell leukaemia virus type 1 (HTLV-1) antigen in the particle agglutination (PA) assay using HTLV-1 antigen-coated gelatin particles. Anti-VZV IgM antibodies were shown to be responsible for this cross-reactivity. Western blot analysis revealed that PA-positive anti-VZV sera reacted with the HTLV-1 gag p19 protein in HTLV-1-infected cells and recombinant p19 protein produced in Escherichia coli. By using a truncated p19, the cross-reactive region was located to the C-terminal 17 amino acids of p19. One oligopeptide derived from the C terminus, PQIPPPYVEPT (amino acids 115 to 125), was capable of inhibiting PA, suggesting that this peptide carries the cross-reactive epitope. A homologous sequence was found in the VZV gene 22 protein by database analysis, and the oligopeptide TNIPPPLALLR (amino acids 1330 to 1340) had the ability to inhibit PA. These findings suggest that some IgM antibodies against the VZV gene 22 protein produced in the early phase of VZV infection are cross-reactive with the HTLV-1 gag p19 protein because they recognize an antigenic determinant containing an IPPP tetrapeptide."} {"id": "PMID:1279105", "title": "Infection of macaque monkeys with a chimeric human and simian immunodeficiency virus.", "content": "Two macaque monkeys were inoculated with a chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu and env genes of human immunodeficiency virus type 1. Infectious virus was recovered from one of the monkeys at 2 and 6 weeks post-infection. The hybrid nature of the isolated viruses was verified by Southern and Western blotting analyses. Both of the monkeys infected with the chimera elicited a humoral antibody response against the virus.", "contents": "Infection of macaque monkeys with a chimeric human and simian immunodeficiency virus. Two macaque monkeys were inoculated with a chimeric human and simian immunodeficiency virus carrying the tat, rev, vpu and env genes of human immunodeficiency virus type 1. Infectious virus was recovered from one of the monkeys at 2 and 6 weeks post-infection. The hybrid nature of the isolated viruses was verified by Southern and Western blotting analyses. Both of the monkeys infected with the chimera elicited a humoral antibody response against the virus."} {"id": "PMID:1279106", "title": "Nuclear localization of dengue 2 virus core protein detected with monoclonal antibodies.", "content": "Anti-dengue 2 virus core protein monoclonal antibodies (MAbs) reacted with antigens in the cytoplasm and in, or on, the nucleus of dengue 2 and dengue 4, but not dengue 1, dengue 3, Kunjin or Murray Valley encephalitis virus-infected cells. These MAbs also reacted with the core protein from dengue 1, 2 and 4 virions in Western blots. The antigens detected by these MAbs could not be detected in uninfected or heat-shocked cells, but were first detected in infected cells approximately 32 h post-infection. PEPSCAN epitope mapping suggested that all the MAbs react with a region of the dengue 2 virus core protein (9RNTPFNMLKRE19) which is adjacent to a putative nuclear localization sequence (6KKAR9) and spans a possible second site for the initiation of synthesis of core protein (12PFN decreases MLKR18).", "contents": "Nuclear localization of dengue 2 virus core protein detected with monoclonal antibodies. Anti-dengue 2 virus core protein monoclonal antibodies (MAbs) reacted with antigens in the cytoplasm and in, or on, the nucleus of dengue 2 and dengue 4, but not dengue 1, dengue 3, Kunjin or Murray Valley encephalitis virus-infected cells. These MAbs also reacted with the core protein from dengue 1, 2 and 4 virions in Western blots. The antigens detected by these MAbs could not be detected in uninfected or heat-shocked cells, but were first detected in infected cells approximately 32 h post-infection. PEPSCAN epitope mapping suggested that all the MAbs react with a region of the dengue 2 virus core protein (9RNTPFNMLKRE19) which is adjacent to a putative nuclear localization sequence (6KKAR9) and spans a possible second site for the initiation of synthesis of core protein (12PFN decreases MLKR18)."} {"id": "PMID:1279107", "title": "Immunodetection of grapevine fanleaf virus satellite RNA-encoded protein in infected Chenopodium quinoa.", "content": "An antiserum was raised against a fusion protein containing the C-terminal half of the protein (P3) encoded by the satellite RNA of grapevine fanleaf virus (GFLV; F13 isolate) and the N-terminal portion of the CI repressor of phage lambda. This antiserum specifically recognized P3 synthesized in the in vitro wheatgerm translation system and also in infected Chenopodium quinoa plants. In these plants, the amount of virus increased for 10 days, then remained constant for up to 21 days, whereas P3 was detected transiently, reaching its maximum on day 10.", "contents": "Immunodetection of grapevine fanleaf virus satellite RNA-encoded protein in infected Chenopodium quinoa. An antiserum was raised against a fusion protein containing the C-terminal half of the protein (P3) encoded by the satellite RNA of grapevine fanleaf virus (GFLV; F13 isolate) and the N-terminal portion of the CI repressor of phage lambda. This antiserum specifically recognized P3 synthesized in the in vitro wheatgerm translation system and also in infected Chenopodium quinoa plants. In these plants, the amount of virus increased for 10 days, then remained constant for up to 21 days, whereas P3 was detected transiently, reaching its maximum on day 10."} {"id": "PMID:1279108", "title": "The interrelationship between HBV-markers and HIV antibodies in patients with hepatocellular carcinoma.", "content": "To determine the interrelationship between hepatitis B viral markers (HBV), the human Immunodeficiency virus (HIV), and hepatocellular carcinoma (HCC) in HCC patients, a total of 282 subjects were included in the study. Out of 282 subjects, 182 were HCC patients as determined by raised alpha-feto-protein (AFP) of greater than 1,000 ng/ml. The other 100 control patients presented with other conditions and had detectable AFP of less than 1,000 ng/ml in their sera. On presentation, 10 ml of venous blood was drawn from each enrolled subject and taken to the laboratory. HBV markers were detected using commercial reagents; HIV antibodies were detected by the commercial ELISA tests and were confirmed by Western blot. AFP was detected using an RIA technique. Of 282 examined subjects 182 (64.5%) had detectable AFP of greater than 1,000 ng/ml. 113 (40.1%) and 103 (36.5%) had HBsAg and Anti-HBc respectively. However, HBeAg was found in 21 of 113 (18.6%) of the HBsAg positive only. Anti-HIV antibodies were present in 15 (5.3%) of the 282 tested individuals. Only 1 (1.0%) of the control group had detectable anti-HIV antibodies in the serum. Eleven percent and 4.0% of the same control group had HBsAg and anti-HBc in their sera respectively. The study shows a significant correlation between HCC and HBV-markers (P less than 0.0001). Similarly, a significant correlation between anti-HIV antibodies and HBV-markers, (P less than 0.0001) was found.", "contents": "The interrelationship between HBV-markers and HIV antibodies in patients with hepatocellular carcinoma. To determine the interrelationship between hepatitis B viral markers (HBV), the human Immunodeficiency virus (HIV), and hepatocellular carcinoma (HCC) in HCC patients, a total of 282 subjects were included in the study. Out of 282 subjects, 182 were HCC patients as determined by raised alpha-feto-protein (AFP) of greater than 1,000 ng/ml. The other 100 control patients presented with other conditions and had detectable AFP of less than 1,000 ng/ml in their sera. On presentation, 10 ml of venous blood was drawn from each enrolled subject and taken to the laboratory. HBV markers were detected using commercial reagents; HIV antibodies were detected by the commercial ELISA tests and were confirmed by Western blot. AFP was detected using an RIA technique. Of 282 examined subjects 182 (64.5%) had detectable AFP of greater than 1,000 ng/ml. 113 (40.1%) and 103 (36.5%) had HBsAg and Anti-HBc respectively. However, HBeAg was found in 21 of 113 (18.6%) of the HBsAg positive only. Anti-HIV antibodies were present in 15 (5.3%) of the 282 tested individuals. Only 1 (1.0%) of the control group had detectable anti-HIV antibodies in the serum. Eleven percent and 4.0% of the same control group had HBsAg and anti-HBc in their sera respectively. The study shows a significant correlation between HCC and HBV-markers (P less than 0.0001). Similarly, a significant correlation between anti-HIV antibodies and HBV-markers, (P less than 0.0001) was found."} {"id": "PMID:1279109", "title": "Sensitivity of an anti-HCV core peptide ELISA.", "content": "A newly developed antibody assay based on a synthetic peptide of 15 amino acids derived from the core region of the hepatitis C virus (HCV) genome was evaluated in serum and plasma panels of (A) 225 haemophiliacs and (B) 44 patients with chronic non-A, non-B (NANB) hepatitis, and in (C) sequential serum samples of 9 patients with transfusion transmitted HCV infection. The new anti-core peptide ELISA was compared with the anti-C100 ELISA. For confirmation of HCV infection, samples were tested in a 4-antigen recombinant immunoblot assay (4-RIBA) and samples of panels B and C were also assayed in cDNA-polymerase chain reaction (PCR). In two panels with a high prevalence of HCV infection (88.4 and 70.5% in haemophilia and NANB hepatitis patients, respectively), the sensitivity of the anti-core peptide ELISA did not differ significantly from the sensitivity of the anti-C100 ELISA. The sensitivity of the new assay as compared with the anti-C100 assay was found to be 0.84 [95% confidence interval (CI): 0.78-0.89] versus 0.92 (95% CI: 0.87-0.95) in haemophilia patients and 0.71 (95% CI: 0.52-0.86) versus 0.84 (95% CI: 0.66-0.95) in NANB hepatitis patients. In sequential serum samples of patients with transfusion-transmitted HCV infection antibodies to the core peptide (in 6/9 patients) appeared later than antibodies to C100 (in 7/9 patients): 168 (range: 70-322) and 143 (range: 59-365) days after transfusion, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Sensitivity of an anti-HCV core peptide ELISA. A newly developed antibody assay based on a synthetic peptide of 15 amino acids derived from the core region of the hepatitis C virus (HCV) genome was evaluated in serum and plasma panels of (A) 225 haemophiliacs and (B) 44 patients with chronic non-A, non-B (NANB) hepatitis, and in (C) sequential serum samples of 9 patients with transfusion transmitted HCV infection. The new anti-core peptide ELISA was compared with the anti-C100 ELISA. For confirmation of HCV infection, samples were tested in a 4-antigen recombinant immunoblot assay (4-RIBA) and samples of panels B and C were also assayed in cDNA-polymerase chain reaction (PCR). In two panels with a high prevalence of HCV infection (88.4 and 70.5% in haemophilia and NANB hepatitis patients, respectively), the sensitivity of the anti-core peptide ELISA did not differ significantly from the sensitivity of the anti-C100 ELISA. The sensitivity of the new assay as compared with the anti-C100 assay was found to be 0.84 [95% confidence interval (CI): 0.78-0.89] versus 0.92 (95% CI: 0.87-0.95) in haemophilia patients and 0.71 (95% CI: 0.52-0.86) versus 0.84 (95% CI: 0.66-0.95) in NANB hepatitis patients. In sequential serum samples of patients with transfusion-transmitted HCV infection antibodies to the core peptide (in 6/9 patients) appeared later than antibodies to C100 (in 7/9 patients): 168 (range: 70-322) and 143 (range: 59-365) days after transfusion, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279110", "title": "Hepatitis C viraemia rebound after \"successful\" interferon therapy in patients with chronic non-A, non-B hepatitis.", "content": "A quantitative polymerase chain reaction (PCR) assay for hepatitis C viral RNA (HCV-RNA) was used to monitor viraemia levels in six patients at multiple time points before, during, and after interferon therapy for chronic non-A, non-B hepatitis (NANBH). Prior to therapy, serum HCV-RNA was detected in all patients at approximately 10(4)-10(5) HCV genomes/ml. HCV viraemia became undetectable within 1 month of commencing interferon in three of the five patients whose alanine aminotransferase (ALT) levels decreased to normal on therapy. In the remaining two responder patients, viraemia levels declined more slowly, becoming undetectable after a period of several months. Recurrence of viraemia during therapy was observed in two cases. The one patient whose serum ALT levels remained elevated throughout therapy showed no decline in viraemia. On stopping interferon after a 6 months course, HCV genome titres climbed rapidly in all patients, reaching higher levels than had been observed prior to therapy. Biochemical relapse occurred within 7 months of ending interferon treatment in all but one of the patients who demonstrated this viraemia \"rebound\" phenomenon.", "contents": "Hepatitis C viraemia rebound after \"successful\" interferon therapy in patients with chronic non-A, non-B hepatitis. A quantitative polymerase chain reaction (PCR) assay for hepatitis C viral RNA (HCV-RNA) was used to monitor viraemia levels in six patients at multiple time points before, during, and after interferon therapy for chronic non-A, non-B hepatitis (NANBH). Prior to therapy, serum HCV-RNA was detected in all patients at approximately 10(4)-10(5) HCV genomes/ml. HCV viraemia became undetectable within 1 month of commencing interferon in three of the five patients whose alanine aminotransferase (ALT) levels decreased to normal on therapy. In the remaining two responder patients, viraemia levels declined more slowly, becoming undetectable after a period of several months. Recurrence of viraemia during therapy was observed in two cases. The one patient whose serum ALT levels remained elevated throughout therapy showed no decline in viraemia. On stopping interferon after a 6 months course, HCV genome titres climbed rapidly in all patients, reaching higher levels than had been observed prior to therapy. Biochemical relapse occurred within 7 months of ending interferon treatment in all but one of the patients who demonstrated this viraemia \"rebound\" phenomenon."} {"id": "PMID:1279111", "title": "Inhibition of tyrosine phosphorylation potentiates substrate-induced neurite growth.", "content": "Protein tyrosine kinases (PTKs) have major roles in signal transduction and growth control. There are several lines of evidence implicating PTKs in the regulation of axon growth, and this has led to the suggestion that they are centrally involved in the transduction of neuronal growth signals. To test this idea, we assayed the effect of the compounds genistein and lavendustin, specific inhibitors of PTKs, on neurite growth. We find that genistein greatly reduces phosphotyrosine in neurons, as expected from its action on other cells. Surprisingly, administration of genistein or lavendustin potentiated substrate-induced neurite growth in at least several different neuronal types. Stimulation of neurite growth by genistein was abolished by vanadate, providing additional evidence that inhibition of PTKs is responsible for this effect. The potentiation of growth is rather general, in that it occurs on several different extracellular matrix substrates and on two different cell adhesion molecules. Both the initiation of neurite growth and the rate of neurite elongation appear to be potentiated. Our results do not provide evidence for models of substrate-induced signal transduction that involve PTKs as a positive and necessary step, but suggest that such kinases play a regulatory role in neurite elongation.", "contents": "Inhibition of tyrosine phosphorylation potentiates substrate-induced neurite growth. Protein tyrosine kinases (PTKs) have major roles in signal transduction and growth control. There are several lines of evidence implicating PTKs in the regulation of axon growth, and this has led to the suggestion that they are centrally involved in the transduction of neuronal growth signals. To test this idea, we assayed the effect of the compounds genistein and lavendustin, specific inhibitors of PTKs, on neurite growth. We find that genistein greatly reduces phosphotyrosine in neurons, as expected from its action on other cells. Surprisingly, administration of genistein or lavendustin potentiated substrate-induced neurite growth in at least several different neuronal types. Stimulation of neurite growth by genistein was abolished by vanadate, providing additional evidence that inhibition of PTKs is responsible for this effect. The potentiation of growth is rather general, in that it occurs on several different extracellular matrix substrates and on two different cell adhesion molecules. Both the initiation of neurite growth and the rate of neurite elongation appear to be potentiated. Our results do not provide evidence for models of substrate-induced signal transduction that involve PTKs as a positive and necessary step, but suggest that such kinases play a regulatory role in neurite elongation."} {"id": "PMID:1279112", "title": "Preparation and biological properties of native and recombinant ciliary neurotrophic factor.", "content": "CNTF (ciliary neurotrophic factor), purified from rabbit sciatic nerves by a relatively simple procedure, is bioactive in tissue culture at low picomolar concentration and appears as a doublet on polyacrylamide gel electrophoresis (PAGE). In these nerves, CNTF accounts for more than one-half of the survival-promoting activity on ciliary neurons. The concentration of CNTF in rabbit sciatic nerves is estimated to be 5 nmol/kg, more than 1000 times higher than would seem to be required to support neurons if the neurotrophic factor were homogeneously distributed. With recombinant DNA technology, rat CNTF has been synthesized in Escherichia coli, purified without denaturating agents, and found to be bioactive at a slightly lower concentration than CNTF extracted from rabbit sciatic nerves. After radioiodination, CNTF retains biological activity but is not specifically internalized and retrogradely transported in motor and sensory axons. In peripheral nerves, ciliary neurotrophic factor differs biologically from nerve growth factor (NGF) by its much higher tissue concentration and apparent lack of internalization by peripheral nerve axons.", "contents": "Preparation and biological properties of native and recombinant ciliary neurotrophic factor. CNTF (ciliary neurotrophic factor), purified from rabbit sciatic nerves by a relatively simple procedure, is bioactive in tissue culture at low picomolar concentration and appears as a doublet on polyacrylamide gel electrophoresis (PAGE). In these nerves, CNTF accounts for more than one-half of the survival-promoting activity on ciliary neurons. The concentration of CNTF in rabbit sciatic nerves is estimated to be 5 nmol/kg, more than 1000 times higher than would seem to be required to support neurons if the neurotrophic factor were homogeneously distributed. With recombinant DNA technology, rat CNTF has been synthesized in Escherichia coli, purified without denaturating agents, and found to be bioactive at a slightly lower concentration than CNTF extracted from rabbit sciatic nerves. After radioiodination, CNTF retains biological activity but is not specifically internalized and retrogradely transported in motor and sensory axons. In peripheral nerves, ciliary neurotrophic factor differs biologically from nerve growth factor (NGF) by its much higher tissue concentration and apparent lack of internalization by peripheral nerve axons."} {"id": "PMID:1279113", "title": "Nonintegrin laminin receptors in the nervous system: evidence for lack of a relationship to P40.", "content": "Laminins are extracellular matrix proteins that mediate their effects on cells through integrin and nonintegrin receptors. Two receptors of 67 and 110 kD that bind laminin with a high affinity (Kd approximately nM) have been reported in neural cells. Here, we discuss these and other nonintegrin laminin receptors that have been implicated in neural function. In addition, we report studies characterizing a 43 kD protein, (P40), immunologically related to the 67 kD laminin receptor, which may be involved in retinal development. In our studies, polyclonal antisera (anti-P-20-A) to a synthetic peptide derived from the sequence of a cDNA for a putative high-affinity laminin receptor (67 kD) detected a protein of 43 kD in immunoblots of adult rat retinas. Immunohistochemistry with this antiserum showed that the retinal immunoreactivity was predominantly localized in the ganglion cell layer of both adult chicken and rat retinas where it appeared to be intracellular. Retinal ganglion cells were shown to be immunoreactive by retrogradely labeling them from the superior colliculus with a lipophilic dye and subsequently with anti-P-20-A antisera. Consistent with the preferential localization of the P-20-A immunoreactivity in ganglion cells, there was a substantial decrease in the amounts of P40 on Western blots following optic nerve section and resulting retinal ganglion cell death. Screening of a rat (PC12 cell) cDNA library with the anti-P-20-A antiserum further confirmed the specificity of the antiserum for the rat homologue of P40. Rat P40 is 97% identical to the mouse and 87% identical to human P40 at the nucleic acid level and 98% at the protein level. Restriction mapping of the rather abundant positive clones in the library that cross-hybridized with a human cDNA probe for P40 indicated that the full-length cDNA of 1.2 kb was the major and perhaps the only cDNA in the library. In Northern blots of adult rat retina, these clones hybridized to a single 1.2-kb transcript. Electroblots of retinal homogenates probed with radioiodinated laminin demonstrated binding to a broad band at 110 kD, but none at 43 kD. Taken together these findings suggest that P40 may not be a laminin receptor and are in keeping with the hydrophilic composition of the protein, its intracellular localization, as well as other features predicted by its nucleic acid sequence.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Nonintegrin laminin receptors in the nervous system: evidence for lack of a relationship to P40. Laminins are extracellular matrix proteins that mediate their effects on cells through integrin and nonintegrin receptors. Two receptors of 67 and 110 kD that bind laminin with a high affinity (Kd approximately nM) have been reported in neural cells. Here, we discuss these and other nonintegrin laminin receptors that have been implicated in neural function. In addition, we report studies characterizing a 43 kD protein, (P40), immunologically related to the 67 kD laminin receptor, which may be involved in retinal development. In our studies, polyclonal antisera (anti-P-20-A) to a synthetic peptide derived from the sequence of a cDNA for a putative high-affinity laminin receptor (67 kD) detected a protein of 43 kD in immunoblots of adult rat retinas. Immunohistochemistry with this antiserum showed that the retinal immunoreactivity was predominantly localized in the ganglion cell layer of both adult chicken and rat retinas where it appeared to be intracellular. Retinal ganglion cells were shown to be immunoreactive by retrogradely labeling them from the superior colliculus with a lipophilic dye and subsequently with anti-P-20-A antisera. Consistent with the preferential localization of the P-20-A immunoreactivity in ganglion cells, there was a substantial decrease in the amounts of P40 on Western blots following optic nerve section and resulting retinal ganglion cell death. Screening of a rat (PC12 cell) cDNA library with the anti-P-20-A antiserum further confirmed the specificity of the antiserum for the rat homologue of P40. Rat P40 is 97% identical to the mouse and 87% identical to human P40 at the nucleic acid level and 98% at the protein level. Restriction mapping of the rather abundant positive clones in the library that cross-hybridized with a human cDNA probe for P40 indicated that the full-length cDNA of 1.2 kb was the major and perhaps the only cDNA in the library. In Northern blots of adult rat retina, these clones hybridized to a single 1.2-kb transcript. Electroblots of retinal homogenates probed with radioiodinated laminin demonstrated binding to a broad band at 110 kD, but none at 43 kD. Taken together these findings suggest that P40 may not be a laminin receptor and are in keeping with the hydrophilic composition of the protein, its intracellular localization, as well as other features predicted by its nucleic acid sequence.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279114", "title": "The role of matrix molecules in regeneration of leech CNS.", "content": "Extracellular matrix (ECM) molecules extracted from the leech central nervous system (CNS) provide substrates that induce extensive growth of processes of identified leech nerve cells in culture. Two ECM molecules, laminin and tenascin, have been identified. The laminin-like molecule has been purified and shown to be a cross-shaped molecule similar to vertebrate laminin with subunits of 340, 220, 180, and 160 kD. Purified laminin as a substrate induces rapid outgrowth of Retzius (R) and Anterior Pagoda (AP) cells in culture. The tenascin molecule has been partially purified. In electronmicrographs, leech tenascin, like vertebrate tenascin, has six arms of equal size joined in a central globule. Highly enriched fractions of leech tenascin induce rapid and extensive outgrowth of Retzius and AP cells in culture. Substrate molecules not only induce outgrowth of processes but also affect the growth patterns of individual nerve cells. Neurites are straight with few branches in laminin, but curved with profuse branches on tenascin. During regeneration of the CNS in the animal, laminin appears at new sites associated with growth cones. The appearance of laminin correlates with the accumulation of microglial cells. Thus, ECM molecules with growth-promoting activity for leech nerve cells in vitro appear to be involved in inducing regeneration and allowing the neurites to reconnect with former targets.", "contents": "The role of matrix molecules in regeneration of leech CNS. Extracellular matrix (ECM) molecules extracted from the leech central nervous system (CNS) provide substrates that induce extensive growth of processes of identified leech nerve cells in culture. Two ECM molecules, laminin and tenascin, have been identified. The laminin-like molecule has been purified and shown to be a cross-shaped molecule similar to vertebrate laminin with subunits of 340, 220, 180, and 160 kD. Purified laminin as a substrate induces rapid outgrowth of Retzius (R) and Anterior Pagoda (AP) cells in culture. The tenascin molecule has been partially purified. In electronmicrographs, leech tenascin, like vertebrate tenascin, has six arms of equal size joined in a central globule. Highly enriched fractions of leech tenascin induce rapid and extensive outgrowth of Retzius and AP cells in culture. Substrate molecules not only induce outgrowth of processes but also affect the growth patterns of individual nerve cells. Neurites are straight with few branches in laminin, but curved with profuse branches on tenascin. During regeneration of the CNS in the animal, laminin appears at new sites associated with growth cones. The appearance of laminin correlates with the accumulation of microglial cells. Thus, ECM molecules with growth-promoting activity for leech nerve cells in vitro appear to be involved in inducing regeneration and allowing the neurites to reconnect with former targets."} {"id": "PMID:1279115", "title": "Slow transport of the cytoskeleton after axonal injury.", "content": "The delivery of cytoskeletal proteins to the axon occurs by slow axonal transport. We examined how the rate of slow transport was altered after axonal injury. When retinal ganglion cell (RGC) axons regenerated through peripheral nerve grafts, an increase in the rate of slow transport occurred during regrowth of the injured axons. We compared these results to axonal injury in the optic nerve where no substantial regrowth occurs and found a completely different response. Slow transport was decreased approximately tenfold in rate in the proximal segment of crushed optic nerves. This decreased rate of slow transport was not induced immediately, but occurred about 1 week after injury. To explore whether a decrease in the rate of slow transport was induced when the regeneration of peripheral nerves was physically blocked, we examined slow transport in motor neurons after the sciatic nerve was transected and ligated. In this case, no change in the rate of the comigrating tubulin and neurofilament (NF) radioactive peaks were observed. We discuss how the changes in the rate of slow transport may reflect different neuronal responses to injury and speculate about the possible molecular changes in the expression of tubulin which may contribute to the observed changes.", "contents": "Slow transport of the cytoskeleton after axonal injury. The delivery of cytoskeletal proteins to the axon occurs by slow axonal transport. We examined how the rate of slow transport was altered after axonal injury. When retinal ganglion cell (RGC) axons regenerated through peripheral nerve grafts, an increase in the rate of slow transport occurred during regrowth of the injured axons. We compared these results to axonal injury in the optic nerve where no substantial regrowth occurs and found a completely different response. Slow transport was decreased approximately tenfold in rate in the proximal segment of crushed optic nerves. This decreased rate of slow transport was not induced immediately, but occurred about 1 week after injury. To explore whether a decrease in the rate of slow transport was induced when the regeneration of peripheral nerves was physically blocked, we examined slow transport in motor neurons after the sciatic nerve was transected and ligated. In this case, no change in the rate of the comigrating tubulin and neurofilament (NF) radioactive peaks were observed. We discuss how the changes in the rate of slow transport may reflect different neuronal responses to injury and speculate about the possible molecular changes in the expression of tubulin which may contribute to the observed changes."} {"id": "PMID:1279116", "title": "Sex-dependent loss of projection neurons involved in avian song learning.", "content": "In zebra finches, only males sing, and the neural regions controlling song exhibit prominent, hormone-induced sex differences in neuron number. In order to understand how sexual differentiation regulates neuron number within one song nucleus, the lateral magnocellular nucleus of the anterior neostriatum (IMAN), we studied the development of sex differences among IMAN neurons that project to the robust nucleus of the archistriatum (RA). The IMAN is implicated in song learning, and previous ontogenetic studies have indicated that males lose over 50% of their IMAN neurons during the juvenile song learning period. Based on developmental changes in both the extent of androgen accumulation within the IMAN and its appearance in Nissl-stained tissue, it had been hypothesized that IMAN neuron loss was even greater in young females, resulting in sex differences in neuron number. However, this hypothesis has not been tested directly because the Nissl-stained boundaries of the IMAN sometimes are ambiguous in young animals, and are not evident at all in adult females. To circumvent these problems, we employed the retrograde tracer fast blue to study the development of IMAN neurons defined on the basis of their projections to the RA. We find that the number of these IMAN-RA projection neurons is much greater in adult males than in females, and that this sex difference develops during the juvenile period of sexual differentiation and song learning because a significant number of these neurons are lost in females but not in males. With respect to sexual differentiation, we conclude that masculinization (which is stimulated by the hormone estradiol) promotes the retention of IMAN-RA projection neurons. In addition, our results indicate that any loss of IMAN neurons that may occur in young males does not include cells projecting to the RA.", "contents": "Sex-dependent loss of projection neurons involved in avian song learning. In zebra finches, only males sing, and the neural regions controlling song exhibit prominent, hormone-induced sex differences in neuron number. In order to understand how sexual differentiation regulates neuron number within one song nucleus, the lateral magnocellular nucleus of the anterior neostriatum (IMAN), we studied the development of sex differences among IMAN neurons that project to the robust nucleus of the archistriatum (RA). The IMAN is implicated in song learning, and previous ontogenetic studies have indicated that males lose over 50% of their IMAN neurons during the juvenile song learning period. Based on developmental changes in both the extent of androgen accumulation within the IMAN and its appearance in Nissl-stained tissue, it had been hypothesized that IMAN neuron loss was even greater in young females, resulting in sex differences in neuron number. However, this hypothesis has not been tested directly because the Nissl-stained boundaries of the IMAN sometimes are ambiguous in young animals, and are not evident at all in adult females. To circumvent these problems, we employed the retrograde tracer fast blue to study the development of IMAN neurons defined on the basis of their projections to the RA. We find that the number of these IMAN-RA projection neurons is much greater in adult males than in females, and that this sex difference develops during the juvenile period of sexual differentiation and song learning because a significant number of these neurons are lost in females but not in males. With respect to sexual differentiation, we conclude that masculinization (which is stimulated by the hormone estradiol) promotes the retention of IMAN-RA projection neurons. In addition, our results indicate that any loss of IMAN neurons that may occur in young males does not include cells projecting to the RA."} {"id": "PMID:1279117", "title": "Association of neuronal pp60c-src with growth cone glycoproteins of rat brain.", "content": "Tyrosine phosphorylation and protein tyrosine kinase (PTK) activity in the growth cone membrane-associated glycoprotein (GCGP) fraction of 1-day-old rat brain were examined. Using immunoblotting and immunoprecipitation techniques, pp60c-src was identified as one of the major PTKs associated with GCGPs. Furthermore, only GCGP-associated src that was also tyrosine phosphorylated was active. Immunoprecipitation experiments using various src antibodies revealed that pp60c-src contributed partially to the PTK activity detected in GCGPs, and that it is associated with several proteins of Mr 140 K, 120 K, 85 K and 50 K. This association of src protein with GCGPs was specific, and another src family member p59fyn, which is also abundant in the brain, did not exhibit such an association. In addition to pp60c-src, the GCGP fraction contained several major phosphotyrosine-containing proteins of Mr 140 K, and a 97/90 K doublet that corresponded to the beta subunits of IGF-I/insulin receptors. These studies show that pp60c-src associated with GCGPs is an active PTK that could be involved in neuronal growth and development, transmembrane signalling, and in recognition and/or adhesive events.", "contents": "Association of neuronal pp60c-src with growth cone glycoproteins of rat brain. Tyrosine phosphorylation and protein tyrosine kinase (PTK) activity in the growth cone membrane-associated glycoprotein (GCGP) fraction of 1-day-old rat brain were examined. Using immunoblotting and immunoprecipitation techniques, pp60c-src was identified as one of the major PTKs associated with GCGPs. Furthermore, only GCGP-associated src that was also tyrosine phosphorylated was active. Immunoprecipitation experiments using various src antibodies revealed that pp60c-src contributed partially to the PTK activity detected in GCGPs, and that it is associated with several proteins of Mr 140 K, 120 K, 85 K and 50 K. This association of src protein with GCGPs was specific, and another src family member p59fyn, which is also abundant in the brain, did not exhibit such an association. In addition to pp60c-src, the GCGP fraction contained several major phosphotyrosine-containing proteins of Mr 140 K, and a 97/90 K doublet that corresponded to the beta subunits of IGF-I/insulin receptors. These studies show that pp60c-src associated with GCGPs is an active PTK that could be involved in neuronal growth and development, transmembrane signalling, and in recognition and/or adhesive events."} {"id": "PMID:1279118", "title": "Efficacy of a flowable concentrate formulation of Bacillus thuringiensis (H-14) against larval mosquitoes in southern Iran.", "content": "A flowable concentrate formulation of Bacillus thuringiensis (H-14) [Bactimos FC (1000 ITU/mg)] was evaluated for the control of mosquito larvae in simulated ponds and natural breeding sites in Kazeroun (Fars Province), southern Iran. A comparison was made with Abate emulsifiable concentrate. Bactimos FC caused 93-96% anopheline and 97% culicine larval mortality 24 h posttreatment in simulated ponds and natural breeding sites, when used at the rate of 0.2 cc/m2. Abate (0.015 cc/m2) resulted in significantly higher anopheline (98.1%) and culicine (100%) mortality at 24 h posttreatment. There was a relatively sharp decline in larval mortality 48 h posttreatment when Bactimos FC was applied. Five-day applications were suggested to prevent pupal production.", "contents": "Efficacy of a flowable concentrate formulation of Bacillus thuringiensis (H-14) against larval mosquitoes in southern Iran. A flowable concentrate formulation of Bacillus thuringiensis (H-14) [Bactimos FC (1000 ITU/mg)] was evaluated for the control of mosquito larvae in simulated ponds and natural breeding sites in Kazeroun (Fars Province), southern Iran. A comparison was made with Abate emulsifiable concentrate. Bactimos FC caused 93-96% anopheline and 97% culicine larval mortality 24 h posttreatment in simulated ponds and natural breeding sites, when used at the rate of 0.2 cc/m2. Abate (0.015 cc/m2) resulted in significantly higher anopheline (98.1%) and culicine (100%) mortality at 24 h posttreatment. There was a relatively sharp decline in larval mortality 48 h posttreatment when Bactimos FC was applied. Five-day applications were suggested to prevent pupal production."} {"id": "PMID:1279119", "title": "Oxygen transfer reactions by synthetic analogues of iron-bleomycin.", "content": "Synthetic analogues of the iron-bleomycins, namely [Fe(PMA)]2+ and [Fe(PMA)]+, have been studied as oxotransfer agents. Oxygen transfer has been observed using iodosobenzene (PhIO), hydrogen peroxide, and dioxygen as oxygen sources. The primary substrates were cis- and trans-stilbene. The products were determined to be cis- and trans-stilbene oxide, benzaldehyde, and deoxybenzoin. These products were recovered in ratios similar to those reported for the iron-bleomycins, albeit in lower yields. Iron complexes of simpler analogues are inactive as oxotransfer agents. This study provides further support that PMAH is an accurate model of the metal binding region of bleomycin.", "contents": "Oxygen transfer reactions by synthetic analogues of iron-bleomycin. Synthetic analogues of the iron-bleomycins, namely [Fe(PMA)]2+ and [Fe(PMA)]+, have been studied as oxotransfer agents. Oxygen transfer has been observed using iodosobenzene (PhIO), hydrogen peroxide, and dioxygen as oxygen sources. The primary substrates were cis- and trans-stilbene. The products were determined to be cis- and trans-stilbene oxide, benzaldehyde, and deoxybenzoin. These products were recovered in ratios similar to those reported for the iron-bleomycins, albeit in lower yields. Iron complexes of simpler analogues are inactive as oxotransfer agents. This study provides further support that PMAH is an accurate model of the metal binding region of bleomycin."} {"id": "PMID:1279120", "title": "Evidence that high- and low-affinity DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites reflect membrane-dependent states of a single receptor.", "content": "Binding of DL-alpha-[3H]amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ([3H]AMPA) to lysed rat brain membranes in the presence of potassium thiocyanate resulted in curvilinear Scatchard plots that could be resolved by regression analysis into a large low-affinity component and a small high-affinity component. Solubilization with Triton X-100 resulted in solubilized and nonsolubilized fractions that were considerably enriched in the high-affinity component and correspondingly reduced in the low-affinity component. It thus appears that solubilization converts low-affinity AMPA receptors into high-affinity receptors. Also, synaptic plasma membranes were found to be greatly enriched in the low-affinity form and deficient in the high-affinity form of the AMPA receptor. These experiments provide evidence for the hypothesis that the high- and low-affinity components of AMPA binding are interconvertible states of the same receptor rather than separate binding sites and that the conversion of these receptors from their native high-affinity state to the low-affinity state occurs on insertion of the receptors into synapses.", "contents": "Evidence that high- and low-affinity DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) binding sites reflect membrane-dependent states of a single receptor. Binding of DL-alpha-[3H]amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ([3H]AMPA) to lysed rat brain membranes in the presence of potassium thiocyanate resulted in curvilinear Scatchard plots that could be resolved by regression analysis into a large low-affinity component and a small high-affinity component. Solubilization with Triton X-100 resulted in solubilized and nonsolubilized fractions that were considerably enriched in the high-affinity component and correspondingly reduced in the low-affinity component. It thus appears that solubilization converts low-affinity AMPA receptors into high-affinity receptors. Also, synaptic plasma membranes were found to be greatly enriched in the low-affinity form and deficient in the high-affinity form of the AMPA receptor. These experiments provide evidence for the hypothesis that the high- and low-affinity components of AMPA binding are interconvertible states of the same receptor rather than separate binding sites and that the conversion of these receptors from their native high-affinity state to the low-affinity state occurs on insertion of the receptors into synapses."} {"id": "PMID:1279121", "title": "Regulation of neuronal nitric oxide and cyclic GMP formation by Ca2+.", "content": "Nitric oxide (NO) acts as a messenger molecule in the CNS by activating soluble guanylyl cyclase. Rat brain synaptosomal NO synthase was stimulated by Ca2+ in a concentration-dependent manner with half-maximal effects observed at 0.3 microM and 0.2 microM when its activity was assayed as formation of NO and L-citrulline, respectively. Cyclic GMP formation was apparently inhibited, however, at Ca2+ concentrations required for the activation of NO synthase, indicating a down-regulation of the signal in NO-producing cells. Purified synaptosomal guanylyl cyclase was not inhibited directly by Ca2+, and the effect was not mediated by a protein binding to guanylyl cyclase at low or high Ca2+ concentrations. In cytosolic fractions, the breakdown of cyclic GMP, but not that of cyclic AMP, was highly stimulated by Ca2+, and 3-isobutyl-1-methylxanthine did not block this reaction effectively. The effects of Ca2+ on cyclic GMP hydrolysis and on apparent guanylyl cyclase activities were abolished almost completely in the presence of the calmodulin antagonist calmidazolium, whose effect was attenuated by added calmodulin. Thus, a Ca2+/calmodulin-dependent cyclic GMP phosphodiesterase is highly active in synaptic areas of the brain and may prevent elevations of intracellular cyclic GMP levels in activated, NO-producing neurons.", "contents": "Regulation of neuronal nitric oxide and cyclic GMP formation by Ca2+. Nitric oxide (NO) acts as a messenger molecule in the CNS by activating soluble guanylyl cyclase. Rat brain synaptosomal NO synthase was stimulated by Ca2+ in a concentration-dependent manner with half-maximal effects observed at 0.3 microM and 0.2 microM when its activity was assayed as formation of NO and L-citrulline, respectively. Cyclic GMP formation was apparently inhibited, however, at Ca2+ concentrations required for the activation of NO synthase, indicating a down-regulation of the signal in NO-producing cells. Purified synaptosomal guanylyl cyclase was not inhibited directly by Ca2+, and the effect was not mediated by a protein binding to guanylyl cyclase at low or high Ca2+ concentrations. In cytosolic fractions, the breakdown of cyclic GMP, but not that of cyclic AMP, was highly stimulated by Ca2+, and 3-isobutyl-1-methylxanthine did not block this reaction effectively. The effects of Ca2+ on cyclic GMP hydrolysis and on apparent guanylyl cyclase activities were abolished almost completely in the presence of the calmodulin antagonist calmidazolium, whose effect was attenuated by added calmodulin. Thus, a Ca2+/calmodulin-dependent cyclic GMP phosphodiesterase is highly active in synaptic areas of the brain and may prevent elevations of intracellular cyclic GMP levels in activated, NO-producing neurons."} {"id": "PMID:1279122", "title": "Regulation of the chromaffin granule catecholamine transporter in cultured bovine adrenal medullary cells: stimulus-biosynthesis coupling.", "content": "The transsynaptic induction of the monoamine transporter present on the membrane of chromaffin granules was studied in primary cultures of dissociated bovine adrenomedullary cells submitted to a chronic secretory stimulation. The amount of the vesicular monoamine transporter was assayed by binding of the specific ligand [3H]-dihydrotetrabenazine. After several days of incubation in the presence of high potassium, the concentration of [3H]-dihydrotetrabenazine binding sites was increased by a 1.5-2.5 factor. This increase was smaller in the presence of the cholinergic agonist carbachol. The long-term inductions of the vesicular monoamine transporter, of tyrosine hydroxylase, and of acetylcholinesterase were of similar magnitude. Under the same conditions, we found no variation in either the activities of other catecholamine biosynthetic enzymes (dopamine beta-hydroxylase and DOPA decarboxylase), or in metabolic enzymes such as lactate dehydrogenase and cytochrome c oxidase, and a decrease in the cellular content of chromogranin A and cytochrome b-561. The induction of the vesicular monoamine transporter was inhibited by the calcium channel antagonists, fluspirilene and nifedipine, and was increased by the agonist Bay K 8644. It was abolished by cycloheximide and actinomycin D. These results indicate that calcium entry into chromaffin cells increases the synthesis of the vesicular monoamine transporter, presumably by transcriptional activation. Elevation of intracellular cyclic AMP concentration or activation of protein kinase C also induced an increase in the expression of the vesicular monoamine transporter. Our results confirm that components of storage vesicle membranes are differentially regulated in response to secretory stimulation, as are several cytosolic or intravesicular soluble proteins.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Regulation of the chromaffin granule catecholamine transporter in cultured bovine adrenal medullary cells: stimulus-biosynthesis coupling. The transsynaptic induction of the monoamine transporter present on the membrane of chromaffin granules was studied in primary cultures of dissociated bovine adrenomedullary cells submitted to a chronic secretory stimulation. The amount of the vesicular monoamine transporter was assayed by binding of the specific ligand [3H]-dihydrotetrabenazine. After several days of incubation in the presence of high potassium, the concentration of [3H]-dihydrotetrabenazine binding sites was increased by a 1.5-2.5 factor. This increase was smaller in the presence of the cholinergic agonist carbachol. The long-term inductions of the vesicular monoamine transporter, of tyrosine hydroxylase, and of acetylcholinesterase were of similar magnitude. Under the same conditions, we found no variation in either the activities of other catecholamine biosynthetic enzymes (dopamine beta-hydroxylase and DOPA decarboxylase), or in metabolic enzymes such as lactate dehydrogenase and cytochrome c oxidase, and a decrease in the cellular content of chromogranin A and cytochrome b-561. The induction of the vesicular monoamine transporter was inhibited by the calcium channel antagonists, fluspirilene and nifedipine, and was increased by the agonist Bay K 8644. It was abolished by cycloheximide and actinomycin D. These results indicate that calcium entry into chromaffin cells increases the synthesis of the vesicular monoamine transporter, presumably by transcriptional activation. Elevation of intracellular cyclic AMP concentration or activation of protein kinase C also induced an increase in the expression of the vesicular monoamine transporter. Our results confirm that components of storage vesicle membranes are differentially regulated in response to secretory stimulation, as are several cytosolic or intravesicular soluble proteins.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279123", "title": "Laminin B1 and collagen type IV gene expression in transected peripheral nerve: reinnervation compared to denervation.", "content": "The expression of B1 laminin and type IV collagen was followed in the microsurgically isolated endoneurium of transected rat sciatic nerves from 3 days until 8 weeks. Northern hybridizations revealed that after nerve transection the proximal stumps of denervated, as well as freely regenerating, nerves showed a markedly increased expression of laminin and type IV collagen which lasted from 3 days up to 8 weeks. In the distal stumps, close to the site of transection (2-7 mm), the expression of laminin, and to a certain extent that of type IV collagen, seemed to be enhanced if free axonal reinnervation was allowed. Further distally (10-15 mm), the patterns of B1 laminin and type IV collagen expression were similar in both experimental groups, so that an increased expression was noticed during the first 2 weeks. The present results suggest that laminin and type IV collagen gene expression is markedly different in different parts of transected rat sciatic nerve. During peripheral nerve regeneration, there is a long-lasting basement membrane gene expression in the proximal stump. In the distal part of the transected nerve, the axonal reinnervation possibly up-regulates, but is not essential for, the expression of B1 laminin and type IV collagen.", "contents": "Laminin B1 and collagen type IV gene expression in transected peripheral nerve: reinnervation compared to denervation. The expression of B1 laminin and type IV collagen was followed in the microsurgically isolated endoneurium of transected rat sciatic nerves from 3 days until 8 weeks. Northern hybridizations revealed that after nerve transection the proximal stumps of denervated, as well as freely regenerating, nerves showed a markedly increased expression of laminin and type IV collagen which lasted from 3 days up to 8 weeks. In the distal stumps, close to the site of transection (2-7 mm), the expression of laminin, and to a certain extent that of type IV collagen, seemed to be enhanced if free axonal reinnervation was allowed. Further distally (10-15 mm), the patterns of B1 laminin and type IV collagen expression were similar in both experimental groups, so that an increased expression was noticed during the first 2 weeks. The present results suggest that laminin and type IV collagen gene expression is markedly different in different parts of transected rat sciatic nerve. During peripheral nerve regeneration, there is a long-lasting basement membrane gene expression in the proximal stump. In the distal part of the transected nerve, the axonal reinnervation possibly up-regulates, but is not essential for, the expression of B1 laminin and type IV collagen."} {"id": "PMID:1279124", "title": "Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA.", "content": "The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Tachykinin systems in the spinal cord and basal ganglia: influence of neonatal capsaicin treatment or dopaminergic intervention on levels of peptides, substance P-encoding mRNAs, and substance P receptor mRNA. The aim of the study was to test whether the synthesis of substance P (SP) and that of its receptor (also known as NK1 receptor) are coordinately regulated after chronic pharmacologic intervention in two neural systems, the spinal cord and basal ganglia. In one set of experiments, capsaicin was administered subcutaneously during the early postnatal period (day 3 after birth) to induce degeneration of afferent sensory neurons in the spinal cord. In the other set of experiments, interruption of dopaminergic transmission was achieved by two methods: (a) The neurotoxin 6-hydroxydopamine was used to denervate dopaminergic neurons during the early postnatal period, and (b) haloperidol was used in adult animals to block dopaminergic transmission by receptor blockade. The spinal cord, striatum, or both were used for the quantification of tachykinin [SP and neurokinin A (NKA)] and opioid peptides [[Met5]-enkephalin (ME) and dynorphin A (1-8) (DYN)] by radioimmunoassays. The abundance of total SP-encoding preprotachykinin (PPT) mRNA and SP receptor (SPR) mRNA in spinal cord (C5 to T1 segments), striatum, or microdissected substantia nigra was determined by northern blot or solution hybridization analysis. Amines and their acid metabolites were quantified by HPLC. Capsaicin administration (subcutaneously) during the early postnatal period increased latency in a hot-plate test, decreased SP and NKA levels, increased levels of PPT mRNAs, and did not affect SPR mRNA levels in the spinal cord. Intraspinal SP systems may attempt to compensate for the loss of afferent SP input, whereas spinal cord receptor mRNA levels do not appear to be altered.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279125", "title": "A novel transcript overlapping the myelin basic protein gene.", "content": "Myelin basic protein (MBP) is a major constituent of myelin synthesized by oligodendrocytes and Schwann cells. We have investigated the expression of mouse MBP RNAs outside the nervous system. Nuclease protection experiments indicate that RNAs containing exon 1 and not the six downstream exons of the MBP gene are transcribed in various hemopoietic tissues. We have isolated a hemopoietic MBP-related (HMBPR) cDNA clone from a mouse bone marrow cDNA library screened with an MBP cDNA probe. This clone contains exons 1a and 1b and a part of intron 1 of the MBP gene. An additional 5' region, encoded by at least three unidentified exons, lies upstream of exon 1a. The HMBPR clone corresponds to a 5-kb RNA expressed in bone marrow, spleen, thymus, and macrophagic cells. This transcript is expressed at a similar level in brain, although at a lower level than the classical 2-kb mRNA. These data indicate that a new transcript, overlapping the MBP transcription unit and controlled by a distinct promoter, is expressed in hemopoietic tissues. This RNA might encode a 21-kDa protein sharing a common domain with MBP.", "contents": "A novel transcript overlapping the myelin basic protein gene. Myelin basic protein (MBP) is a major constituent of myelin synthesized by oligodendrocytes and Schwann cells. We have investigated the expression of mouse MBP RNAs outside the nervous system. Nuclease protection experiments indicate that RNAs containing exon 1 and not the six downstream exons of the MBP gene are transcribed in various hemopoietic tissues. We have isolated a hemopoietic MBP-related (HMBPR) cDNA clone from a mouse bone marrow cDNA library screened with an MBP cDNA probe. This clone contains exons 1a and 1b and a part of intron 1 of the MBP gene. An additional 5' region, encoded by at least three unidentified exons, lies upstream of exon 1a. The HMBPR clone corresponds to a 5-kb RNA expressed in bone marrow, spleen, thymus, and macrophagic cells. This transcript is expressed at a similar level in brain, although at a lower level than the classical 2-kb mRNA. These data indicate that a new transcript, overlapping the MBP transcription unit and controlled by a distinct promoter, is expressed in hemopoietic tissues. This RNA might encode a 21-kDa protein sharing a common domain with MBP."} {"id": "PMID:1279126", "title": "Constituents of Eriobotrya japonica. A study of their antiviral properties.", "content": "The CHCl3 extract of Eriobotrya japonica from an Italian source was shown to contain four new triterpene esters, namely, 23-trans-p-coumaroyltormentic acid [1], 23-cis-p-coumaroyltormentic acid [2], 3-O-trans-caffeoyltormentic acid [3], and 3-O-trans-p-coumaroylrotundic acid [4], in addition to three common ursolic acid derivatives 5, 6, and 7. An investigation of the antiviral properties of compounds 1-7 revealed that only 3 significantly reduced rhinovirus infection. The compounds were ineffective towards human immunodeficiency virus type 1 (HIV-1) and Sindbis virus replication.", "contents": "Constituents of Eriobotrya japonica. A study of their antiviral properties. The CHCl3 extract of Eriobotrya japonica from an Italian source was shown to contain four new triterpene esters, namely, 23-trans-p-coumaroyltormentic acid [1], 23-cis-p-coumaroyltormentic acid [2], 3-O-trans-caffeoyltormentic acid [3], and 3-O-trans-p-coumaroylrotundic acid [4], in addition to three common ursolic acid derivatives 5, 6, and 7. An investigation of the antiviral properties of compounds 1-7 revealed that only 3 significantly reduced rhinovirus infection. The compounds were ineffective towards human immunodeficiency virus type 1 (HIV-1) and Sindbis virus replication."} {"id": "PMID:1279127", "title": "Immunochemical and clinical effects of immunosuppressive treatment in monoclonal IgM neuropathy.", "content": "A pathogenic role of the M protein in monoclonal IgM neuropathy has been suggested. This is based among other things on a close relation between immunosuppressive treatment, lowered concentration of M protein, and clinical effect. We studied five patients with monoclonal IgM and antibodies to peripheral nerve myelin. The immunosuppressive treatment was beneficial in three of the patients. In three patients there was a relationship between antibody concentration and clinical effect (in one there was no change in antibody concentrations and correspondingly no change in clinical status, and in two patients clinical improvement corresponded to decreased antibody concentrations). In two patients, however, there was no clear correlation, since one patient improved despite increasing antibody concentrations and one patient did not improve despite a lowered antibody concentration. It is therefore possible that other mechanisms may contribute to the effect of treatment.", "contents": "Immunochemical and clinical effects of immunosuppressive treatment in monoclonal IgM neuropathy. A pathogenic role of the M protein in monoclonal IgM neuropathy has been suggested. This is based among other things on a close relation between immunosuppressive treatment, lowered concentration of M protein, and clinical effect. We studied five patients with monoclonal IgM and antibodies to peripheral nerve myelin. The immunosuppressive treatment was beneficial in three of the patients. In three patients there was a relationship between antibody concentration and clinical effect (in one there was no change in antibody concentrations and correspondingly no change in clinical status, and in two patients clinical improvement corresponded to decreased antibody concentrations). In two patients, however, there was no clear correlation, since one patient improved despite increasing antibody concentrations and one patient did not improve despite a lowered antibody concentration. It is therefore possible that other mechanisms may contribute to the effect of treatment."} {"id": "PMID:1279128", "title": "T cell responses to myelin proteins in Guillain-Barr\u00e9 syndrome.", "content": "We have investigated the hypothesis that the pathogenesis of Guillain-Barr\u00e9 syndrome (GBS) involves an autoimmune T cell response to P0 and P2 proteins of peripheral nerve myelin. The proliferative responses of blood mononuclear cells (MNC) to myelin proteins and synthetic peptides derived from them were determined in patients with GBS and chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), normal controls (NC) and patients with other neuropathies (ONP). Twelve out of 19 GBS patients responded to P0 or P2, 6 to P0 and its peptides only, 3 to P2 and its peptides only, and 3 to both P0 and P2 antigens. Responses to at least one of the antigens were also found in 6/13 of CIDP patients, but in only 4/17 NC and 2/6 ONP. Immune responses in GBS are heterogeneous. The early T cell responses to P0 protein, described here for the first time, may be important in the pathogenesis of some cases.", "contents": "T cell responses to myelin proteins in Guillain-Barr\u00e9 syndrome. We have investigated the hypothesis that the pathogenesis of Guillain-Barr\u00e9 syndrome (GBS) involves an autoimmune T cell response to P0 and P2 proteins of peripheral nerve myelin. The proliferative responses of blood mononuclear cells (MNC) to myelin proteins and synthetic peptides derived from them were determined in patients with GBS and chronic idiopathic demyelinating polyradiculoneuropathy (CIDP), normal controls (NC) and patients with other neuropathies (ONP). Twelve out of 19 GBS patients responded to P0 or P2, 6 to P0 and its peptides only, 3 to P2 and its peptides only, and 3 to both P0 and P2 antigens. Responses to at least one of the antigens were also found in 6/13 of CIDP patients, but in only 4/17 NC and 2/6 ONP. Immune responses in GBS are heterogeneous. The early T cell responses to P0 protein, described here for the first time, may be important in the pathogenesis of some cases."} {"id": "PMID:1279129", "title": "The effects of the loss of target cells upon photoreceptor inputs in the fly's optic lobe.", "content": "The sensitivity of sensory neurons to target cell denervation varies in the CNS. We have examined the effects of surgically interrupting the output axons of the first optic neuropil, or lamina, in the optic lobe of the fly (Musca domestica), upon the receptor terminal inputs to the lamina. Two of the output interneurons are the monopolar cells L1 and L2, which are found as a pair in each of the unit modules or cartridges of the lamina neuropil. The lamina axons of L1 and L2 degenerate rapidly (within 0.5 h) in a retrograde direction from their lesion site, but there is no sign of retrograde transneuronal degeneration to the receptor terminals, across the input synapse. At each of these synaptic sites, L1 and L2 are invariable contributors to two of the four elements of a postsynaptic tetrad. Not only do the receptor terminals persist, but the presynaptic ribbons at the tetrad sites do also, opposite the degenerated spines of L1 and L2, indicating their lack of target dependence at least over the longest period of post-lesion recovery (48 h) examined. The areal density of presynaptic sites was conserved in the face of the degenerative loss of L1 and L2, as were the numbers of capitate projections (glial invaginations into receptor terminals). The stability of both synaptic density and capitate projection number indicates that they are predominantly influenced by the receptor terminals, which are still intact. A reduction in the number of mitochondrial profiles was one of the few observed changes in the receptor terminals. The results reflect the autonomy which the terminals have, during development, from their interneurons; they especially reflect the role of the terminals in the adult, in maintaining the presynaptic site of their afferent synapses, the tetrads.", "contents": "The effects of the loss of target cells upon photoreceptor inputs in the fly's optic lobe. The sensitivity of sensory neurons to target cell denervation varies in the CNS. We have examined the effects of surgically interrupting the output axons of the first optic neuropil, or lamina, in the optic lobe of the fly (Musca domestica), upon the receptor terminal inputs to the lamina. Two of the output interneurons are the monopolar cells L1 and L2, which are found as a pair in each of the unit modules or cartridges of the lamina neuropil. The lamina axons of L1 and L2 degenerate rapidly (within 0.5 h) in a retrograde direction from their lesion site, but there is no sign of retrograde transneuronal degeneration to the receptor terminals, across the input synapse. At each of these synaptic sites, L1 and L2 are invariable contributors to two of the four elements of a postsynaptic tetrad. Not only do the receptor terminals persist, but the presynaptic ribbons at the tetrad sites do also, opposite the degenerated spines of L1 and L2, indicating their lack of target dependence at least over the longest period of post-lesion recovery (48 h) examined. The areal density of presynaptic sites was conserved in the face of the degenerative loss of L1 and L2, as were the numbers of capitate projections (glial invaginations into receptor terminals). The stability of both synaptic density and capitate projection number indicates that they are predominantly influenced by the receptor terminals, which are still intact. A reduction in the number of mitochondrial profiles was one of the few observed changes in the receptor terminals. The results reflect the autonomy which the terminals have, during development, from their interneurons; they especially reflect the role of the terminals in the adult, in maintaining the presynaptic site of their afferent synapses, the tetrads."} {"id": "PMID:1279130", "title": "Regeneration of adult rat CNS axons into peripheral nerve autografts: ultrastructural studies of the early stages of axonal sprouting and regenerative axonal growth.", "content": "If one end of a segment of peripheral nerve is inserted into the brain or spinal cord, neuronal perikarya in the vicinity of the graft tip can be labelled with retrogradely transported tracers applied to the distal end of the graft several weeks later, showing that CNS axons can regenerate into and along such grafts. We have used transmission EM to examine some of the cellular responses that underlie this regenerative phenomenon, particularly its early stages. Segments of autologous peroneal or tibial nerve were inserted vertically into the thalamus of anaesthetized adult albino rats. The distal end of the graft was left beneath the scalp. Between five days and two months later the animals were killed and the brains prepared for ultrastructural study. Semi-thin and thin sections through the graft and surrounding brain were examined at two levels 6-7 mm apart in all animals: close to the tip of the graft in the thalamus (proximal graft) and at the top of the cerebral cortex (distal graft). In another series of animals with similar grafts, horseradish peroxidase was applied to the distal end of the graft 24-48 h before death. Examination by LM of appropriately processed serial coronal sections of the brains from these animals confirmed that up to several hundred neurons were retrogradely labelled in the thalamus, particularly in the thalamic reticular nucleus. Between five and 14 days after grafting, large numbers of tiny (0.05-0.20 microns diameter) nonmyelinated axonal profiles, considered to be axonal sprouts, were observed by EM within the narrow zone of abnormal thalamic parenchyma bordering the graft. The sprouts were much more numerous (commonly in large fascicles), smoother surfaced, and more rounded than nonmyelinated axons further from the graft or in corresponding areas on the contralateral side of animals with implants or in normal animals. At longer post-graft survival times, the number of such axons in the parenchyma around the graft declined. At five days, some axonal sprouts had entered the junctional zone between the brain and the graft. By eight days there were many sprouts in the junctional zone and some had penetrated the proximal graft to lie between its basal lamina-enclosed columns of Schwann cells, macrophages and myelin debris. Within the brain, sprouts were in contact predominantly with other sprouts but also with all types of glial cell.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Regeneration of adult rat CNS axons into peripheral nerve autografts: ultrastructural studies of the early stages of axonal sprouting and regenerative axonal growth. If one end of a segment of peripheral nerve is inserted into the brain or spinal cord, neuronal perikarya in the vicinity of the graft tip can be labelled with retrogradely transported tracers applied to the distal end of the graft several weeks later, showing that CNS axons can regenerate into and along such grafts. We have used transmission EM to examine some of the cellular responses that underlie this regenerative phenomenon, particularly its early stages. Segments of autologous peroneal or tibial nerve were inserted vertically into the thalamus of anaesthetized adult albino rats. The distal end of the graft was left beneath the scalp. Between five days and two months later the animals were killed and the brains prepared for ultrastructural study. Semi-thin and thin sections through the graft and surrounding brain were examined at two levels 6-7 mm apart in all animals: close to the tip of the graft in the thalamus (proximal graft) and at the top of the cerebral cortex (distal graft). In another series of animals with similar grafts, horseradish peroxidase was applied to the distal end of the graft 24-48 h before death. Examination by LM of appropriately processed serial coronal sections of the brains from these animals confirmed that up to several hundred neurons were retrogradely labelled in the thalamus, particularly in the thalamic reticular nucleus. Between five and 14 days after grafting, large numbers of tiny (0.05-0.20 microns diameter) nonmyelinated axonal profiles, considered to be axonal sprouts, were observed by EM within the narrow zone of abnormal thalamic parenchyma bordering the graft. The sprouts were much more numerous (commonly in large fascicles), smoother surfaced, and more rounded than nonmyelinated axons further from the graft or in corresponding areas on the contralateral side of animals with implants or in normal animals. At longer post-graft survival times, the number of such axons in the parenchyma around the graft declined. At five days, some axonal sprouts had entered the junctional zone between the brain and the graft. By eight days there were many sprouts in the junctional zone and some had penetrated the proximal graft to lie between its basal lamina-enclosed columns of Schwann cells, macrophages and myelin debris. Within the brain, sprouts were in contact predominantly with other sprouts but also with all types of glial cell.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279131", "title": "Nodes of Ranvier and myelin sheath dimensions along exceptionally thin myelinated vertebrate PNS axons.", "content": "The trigeminal alveolar branch in the lower jaw of the cichlid Tilapia mariae was examined by light and electron microscopy on single and serial sections, and by light microscopy on teased fibre preparations. The principal purpose was to find out if the exceptionally thin myelinated axons (d < 1 micron) present in this nerve possess true nodes of Ranvier, and to determine the dimensions of their myelin sheaths. This necessitated analysis of the whole size range of myelinated fibres, with respect to nodal and internodal morphology. The results show that the exceptionally thin myelinated fibres exhibit primitive nodal regions, with patches of axolemmal undercoating, and few Schwann cell processes in the node gap. This contrasts with the more complex nodal organization seen in larger trigeminal alveolar branch fibres. For the whole population of myelinated fibres the number of myelin lamellae increases rectilinearly with axon diameter, and sheath length increases with fibre diameter according to a logarithmic expression. The myelin sheaths of the exceptionally thin trigeminal alveolar branch fibres are composed of 10-20 lamellae, and extend 35-50 microns along the axon. These results show that the structural complexity of nodal regions in the trigeminal alveolar branch decreases with decreasing fibre size, that the exceptionally thin myelinated trigeminal alveolar branch fibres possess primitive nodes and that they have very short myelin sheaths. Our crude theoretical calculations suggest that these fibres might be capable of saltatory conduction.", "contents": "Nodes of Ranvier and myelin sheath dimensions along exceptionally thin myelinated vertebrate PNS axons. The trigeminal alveolar branch in the lower jaw of the cichlid Tilapia mariae was examined by light and electron microscopy on single and serial sections, and by light microscopy on teased fibre preparations. The principal purpose was to find out if the exceptionally thin myelinated axons (d < 1 micron) present in this nerve possess true nodes of Ranvier, and to determine the dimensions of their myelin sheaths. This necessitated analysis of the whole size range of myelinated fibres, with respect to nodal and internodal morphology. The results show that the exceptionally thin myelinated fibres exhibit primitive nodal regions, with patches of axolemmal undercoating, and few Schwann cell processes in the node gap. This contrasts with the more complex nodal organization seen in larger trigeminal alveolar branch fibres. For the whole population of myelinated fibres the number of myelin lamellae increases rectilinearly with axon diameter, and sheath length increases with fibre diameter according to a logarithmic expression. The myelin sheaths of the exceptionally thin trigeminal alveolar branch fibres are composed of 10-20 lamellae, and extend 35-50 microns along the axon. These results show that the structural complexity of nodal regions in the trigeminal alveolar branch decreases with decreasing fibre size, that the exceptionally thin myelinated trigeminal alveolar branch fibres possess primitive nodes and that they have very short myelin sheaths. Our crude theoretical calculations suggest that these fibres might be capable of saltatory conduction."} {"id": "PMID:1279132", "title": "Hyperventilation as the initial manifestation of lymphomatous meningitis.", "content": "We present the case of a 57 year old man who developed a B-cell lymphoma which involved his lymph nodes, liver, spleen, bone marrow, and peripheral blood. Shortly after attaining a complete remission with chemotherapy, the patient developed profound hyperventilation with no apparent cardiac or pulmonary cause. After one month, the patient developed a 7th nerve palsy and a subsequent work-up demonstrated that he had lymphomatous meningitis. The hyperventilation resolved completely with intrathecal chemotherapy, although the patient eventually died of widely disseminated lymphoma.", "contents": "Hyperventilation as the initial manifestation of lymphomatous meningitis. We present the case of a 57 year old man who developed a B-cell lymphoma which involved his lymph nodes, liver, spleen, bone marrow, and peripheral blood. Shortly after attaining a complete remission with chemotherapy, the patient developed profound hyperventilation with no apparent cardiac or pulmonary cause. After one month, the patient developed a 7th nerve palsy and a subsequent work-up demonstrated that he had lymphomatous meningitis. The hyperventilation resolved completely with intrathecal chemotherapy, although the patient eventually died of widely disseminated lymphoma."} {"id": "PMID:1279133", "title": "Voltage-dependent ionic currents in solitary horizontal cells isolated from cat retina.", "content": "1. Horizontal cells of the cat retina were isolated by enzymatic dissociation. Two types of horizontal cells were identified: the axonless (A-type) horizontal cell having four to six thick, long (approximately 100 microns) dendrites, and the short-axon (B-type) horizontal cell having many (> 5) fine, short (approximately 30 microns) dendrites. 2. Membrane properties of isolated horizontal cells were analyzed under current-clamp and voltage-clamp conditions. In the A-type cell, the average resting potential was -55 mV and the mean membrane capacitance was 110 pF, whereas values in the B-type cell were -58 mV and 40 pF, respectively. The A-type cell showed long-lasting Ca spikes, but B-type cells had no Ca spikes. 3. Five types of voltage-dependent ionic currents were recorded: a sodium current (INa), a calcium current (ICa), and three types of potassium currents. Potassium currents consisted of potassium current through the inward rectifier (Ianomal), transient outward potassium current (IA), and potassium current through the delayed rectifier (IK(v)). INa was recorded only from A-type cells. Other currents were recorded from both types of cells. 4. INa activated when cells were depolarized from a holding potential (Vh) of -95 mV, and it was maximal at -25 mV. This current was blocked by tetrodotoxin. Approximately half of the A-type cells had INa, but no B-type cell had this current. 5. L-type ICa, an inward-going sustained current, was activated with depolarization more positive than -25 mV. Current amplitude reached a maximal value near 15 mV and became smaller with further depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Voltage-dependent ionic currents in solitary horizontal cells isolated from cat retina. 1. Horizontal cells of the cat retina were isolated by enzymatic dissociation. Two types of horizontal cells were identified: the axonless (A-type) horizontal cell having four to six thick, long (approximately 100 microns) dendrites, and the short-axon (B-type) horizontal cell having many (> 5) fine, short (approximately 30 microns) dendrites. 2. Membrane properties of isolated horizontal cells were analyzed under current-clamp and voltage-clamp conditions. In the A-type cell, the average resting potential was -55 mV and the mean membrane capacitance was 110 pF, whereas values in the B-type cell were -58 mV and 40 pF, respectively. The A-type cell showed long-lasting Ca spikes, but B-type cells had no Ca spikes. 3. Five types of voltage-dependent ionic currents were recorded: a sodium current (INa), a calcium current (ICa), and three types of potassium currents. Potassium currents consisted of potassium current through the inward rectifier (Ianomal), transient outward potassium current (IA), and potassium current through the delayed rectifier (IK(v)). INa was recorded only from A-type cells. Other currents were recorded from both types of cells. 4. INa activated when cells were depolarized from a holding potential (Vh) of -95 mV, and it was maximal at -25 mV. This current was blocked by tetrodotoxin. Approximately half of the A-type cells had INa, but no B-type cell had this current. 5. L-type ICa, an inward-going sustained current, was activated with depolarization more positive than -25 mV. Current amplitude reached a maximal value near 15 mV and became smaller with further depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279134", "title": "Electrophysiology of the mammillary complex in vitro. I. Tuberomammillary and lateral mammillary neurons.", "content": "1. The electrophysiological properties of the tuberomammillary and lateral mammillary neurons in the guinea pig mammillary body were studied using an in vitro brain slice preparation. 2. Tuberomammillary (n = 79) neurons were recorded mainly ventral to the lateral mammillary body as well as ventromedially to the fornix within the rostral part of the medial mammillary nucleus. Intracellular staining with horseradish peroxidase (n = 9) and Lucifer yellow (n = 3) revealed that these cells have several thick, long, spiny dendrites emerging from large (20-35 microns) fusiform somata. 3. Most tuberomammillary neurons (66%) fired spontaneously at a relatively low frequency (0.5-10 Hz) at the resting membrane potential. The action potentials were broad (2.3 ms) with a prominent Ca(2+)-dependent shoulder on the falling phase. Deep (17.8 mV), long-lasting spike afterhyperpolarizations were largely Ca(2+)-independent. 4. All tuberomammillary neurons recorded displayed pronounced delayed firing when the cells were activated from a potential negative to the resting level. The cells also displayed a delayed return to the baseline at the break of hyperpolarizing pulses applied from a membrane potential level close to firing threshold. Analysis of the voltage- and time dependence of this delayed rectification suggested the presence of a transient outward current similar to the A current (IA). These were not completely blocked by high concentrations of 4-aminopyridine, whereas the delayed onset of firing was always abolished when voltage-dependent Ca2+ conductances were blocked by superfusion with Cd2+. 5. Tuberomammillary neurons also displayed inward rectification in the hyperpolarizing and, primarily, depolarizing range. Block of voltage-gated Na(+)-dependent conductances with tetrodotoxin (TTX) selectively abolished inward rectification in the depolarizing range, indicating the presence of a persistent low-threshold sodium-dependent conductance (gNap). In fact, persistent TTX-sensitive, plateau potentials were always elicited following Ca2+ block with Cd2+ when K+ currents were reduced by superfusion with tetraethylammonium. 6. The gNap in tuberomammillary neurons may subserve the pacemaker current underlying the spontaneous firing of these cells. The large-amplitude spike afterhyperpolarization of these neurons sets the availability of the transient outward rectifier, which, in conjunction with the pacemaker current, establishes the rate at which membrane potential approaches spike threshold. 7. Repetitive firing elicited by direct depolarization enhanced the spike shoulder of tuberomammillary neurons. Spike trains were followed by a Ca(2+)-dependent, apamine-sensitive, slow afterhyperpolarization. 8. Lateral mammillary neurons were morphologically and electrophysiologically different from tuberomammillary neurons. All lateral mammillary neurons neurons recorded (n = 44) were silent at rest (-60 mV).(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Electrophysiology of the mammillary complex in vitro. I. Tuberomammillary and lateral mammillary neurons. 1. The electrophysiological properties of the tuberomammillary and lateral mammillary neurons in the guinea pig mammillary body were studied using an in vitro brain slice preparation. 2. Tuberomammillary (n = 79) neurons were recorded mainly ventral to the lateral mammillary body as well as ventromedially to the fornix within the rostral part of the medial mammillary nucleus. Intracellular staining with horseradish peroxidase (n = 9) and Lucifer yellow (n = 3) revealed that these cells have several thick, long, spiny dendrites emerging from large (20-35 microns) fusiform somata. 3. Most tuberomammillary neurons (66%) fired spontaneously at a relatively low frequency (0.5-10 Hz) at the resting membrane potential. The action potentials were broad (2.3 ms) with a prominent Ca(2+)-dependent shoulder on the falling phase. Deep (17.8 mV), long-lasting spike afterhyperpolarizations were largely Ca(2+)-independent. 4. All tuberomammillary neurons recorded displayed pronounced delayed firing when the cells were activated from a potential negative to the resting level. The cells also displayed a delayed return to the baseline at the break of hyperpolarizing pulses applied from a membrane potential level close to firing threshold. Analysis of the voltage- and time dependence of this delayed rectification suggested the presence of a transient outward current similar to the A current (IA). These were not completely blocked by high concentrations of 4-aminopyridine, whereas the delayed onset of firing was always abolished when voltage-dependent Ca2+ conductances were blocked by superfusion with Cd2+. 5. Tuberomammillary neurons also displayed inward rectification in the hyperpolarizing and, primarily, depolarizing range. Block of voltage-gated Na(+)-dependent conductances with tetrodotoxin (TTX) selectively abolished inward rectification in the depolarizing range, indicating the presence of a persistent low-threshold sodium-dependent conductance (gNap). In fact, persistent TTX-sensitive, plateau potentials were always elicited following Ca2+ block with Cd2+ when K+ currents were reduced by superfusion with tetraethylammonium. 6. The gNap in tuberomammillary neurons may subserve the pacemaker current underlying the spontaneous firing of these cells. The large-amplitude spike afterhyperpolarization of these neurons sets the availability of the transient outward rectifier, which, in conjunction with the pacemaker current, establishes the rate at which membrane potential approaches spike threshold. 7. Repetitive firing elicited by direct depolarization enhanced the spike shoulder of tuberomammillary neurons. Spike trains were followed by a Ca(2+)-dependent, apamine-sensitive, slow afterhyperpolarization. 8. Lateral mammillary neurons were morphologically and electrophysiologically different from tuberomammillary neurons. All lateral mammillary neurons neurons recorded (n = 44) were silent at rest (-60 mV).(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279135", "title": "Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons.", "content": "1. To perform simulations of the various modes of action potential generation in thalamic relay neurons, we developed Hodgkin-and-Huxley style mathematical equations that describe the voltage dependence and kinetics of activation and inactivation of four different currents, including the transient, low-voltage-activated Ca2+ current (IT), the rapidly inactivating transient K+ current (IA), the slowly inactivating K+ current (IK2), and the hyperpolarization-activated, mixed cationic current (Ih). The modeled currents were derived either from acutely dissociated rat thalamic relay neurons (IT, IA, IK2), or from guinea pig thalamic relay cells maintained in slices in vitro (Ih). 2. The voltage dependence of steady-state activation and inactivation of IT, IA, and IK2 and the activation of Ih could be modeled with Boltzmann-style equations. Modeling of the behavior of IT to depolarizing steps in voltage clamp required the use of the constant field equation to relate permeability to T-current amplitude. The time constant of activation of IT was described by a continuous bell-shaped function with a maximum near 15 ms at threshold for activation (-75 mV) and 23 degrees C. Mathematical description of the kinetics of inactivation and removal of inactivation of this current required two separate functions. 3. The rapidly activating and inactivating K+ current IA was modeled by assuming two components with different time constants of inactivation. The kinetics of activation was described as a continuous function of voltage with the slowest time constant, near 2.5 ms, at threshold for activation (-60 mV) and 23 degrees C. In contrast, the kinetics of inactivation of both components were described as voltage independent, consistent with experimental data. The rate or removal of inactivation of both components of IA was described as continuously increasing with the degree of hyperpolarization. 4. The slowly inactivating K+ current IK2 was also modeled by assuming two components with different rates of inactivation. The kinetics of activation were described by a bell-shaped function with a maximum time constant near 80 ms at -40 mV and 23 degrees C, whereas threshold for activation was approximately -60 mV. Inactivation of both components was modeled as relatively independent of voltage, whereas removal of inactivation was described as a continuous function of membrane potential. 5. The hyperpolarization-activation cationic current, Ih, was modeled by assuming that the current activates with a single exponential relation and does not inactivate.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons. 1. To perform simulations of the various modes of action potential generation in thalamic relay neurons, we developed Hodgkin-and-Huxley style mathematical equations that describe the voltage dependence and kinetics of activation and inactivation of four different currents, including the transient, low-voltage-activated Ca2+ current (IT), the rapidly inactivating transient K+ current (IA), the slowly inactivating K+ current (IK2), and the hyperpolarization-activated, mixed cationic current (Ih). The modeled currents were derived either from acutely dissociated rat thalamic relay neurons (IT, IA, IK2), or from guinea pig thalamic relay cells maintained in slices in vitro (Ih). 2. The voltage dependence of steady-state activation and inactivation of IT, IA, and IK2 and the activation of Ih could be modeled with Boltzmann-style equations. Modeling of the behavior of IT to depolarizing steps in voltage clamp required the use of the constant field equation to relate permeability to T-current amplitude. The time constant of activation of IT was described by a continuous bell-shaped function with a maximum near 15 ms at threshold for activation (-75 mV) and 23 degrees C. Mathematical description of the kinetics of inactivation and removal of inactivation of this current required two separate functions. 3. The rapidly activating and inactivating K+ current IA was modeled by assuming two components with different time constants of inactivation. The kinetics of activation was described as a continuous function of voltage with the slowest time constant, near 2.5 ms, at threshold for activation (-60 mV) and 23 degrees C. In contrast, the kinetics of inactivation of both components were described as voltage independent, consistent with experimental data. The rate or removal of inactivation of both components of IA was described as continuously increasing with the degree of hyperpolarization. 4. The slowly inactivating K+ current IK2 was also modeled by assuming two components with different rates of inactivation. The kinetics of activation were described by a bell-shaped function with a maximum time constant near 80 ms at -40 mV and 23 degrees C, whereas threshold for activation was approximately -60 mV. Inactivation of both components was modeled as relatively independent of voltage, whereas removal of inactivation was described as a continuous function of membrane potential. 5. The hyperpolarization-activation cationic current, Ih, was modeled by assuming that the current activates with a single exponential relation and does not inactivate.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279136", "title": "Association and release of the amyloid protein precursor of Alzheimer's disease from chick brain extracellular matrix.", "content": "The amyloid protein precursor (APP) of Alzheimer's disease was found to bind saturably (Kd = 60 nM) to embryonic chick brain extracellular matrix (ECM). The binding of APP to ECM was not inhibited by 10 micrograms/ml heparin or heparan sulfate. However, pretreatment of cells with 1 mM 4-methylumbelliferyl-beta-D-xyloside, an inhibitor of proteoglycan biosynthesis, reduced the number of APP binding sites on the ECM by 80%. The binding of APP to ECM was also inhibited by pretreatment with chlorate, an inhibitor of glycan sulfation, and heparitinase, which digests the carbohydrate component of heparan sulfate proteoglycans. These results suggest that APP binds with high affinity to one or more heparan sulfate proteoglycans. Acidic and basic fibroblasts growth factor (FGF) also bound to chick ECM. When ECM was incubated with a protease associated with the enzyme AChE (AChE-AP), APP and acidic FGF were released intact from the matrix. The AChE-AP was at least 100-fold more potent in releasing APP from ECM than other trypsin-like proteases (trypsin, plasmin, thrombin). The action of the AChE-AP was inhibited by glia-derived nexin (protease nexin I) and by human brain APP at low nanomolar concentrations. These results suggest that in vivo an AChE-AP may cleave ECM proteins to regulate the availability of soluble APP or other factors bound to the ECM.", "contents": "Association and release of the amyloid protein precursor of Alzheimer's disease from chick brain extracellular matrix. The amyloid protein precursor (APP) of Alzheimer's disease was found to bind saturably (Kd = 60 nM) to embryonic chick brain extracellular matrix (ECM). The binding of APP to ECM was not inhibited by 10 micrograms/ml heparin or heparan sulfate. However, pretreatment of cells with 1 mM 4-methylumbelliferyl-beta-D-xyloside, an inhibitor of proteoglycan biosynthesis, reduced the number of APP binding sites on the ECM by 80%. The binding of APP to ECM was also inhibited by pretreatment with chlorate, an inhibitor of glycan sulfation, and heparitinase, which digests the carbohydrate component of heparan sulfate proteoglycans. These results suggest that APP binds with high affinity to one or more heparan sulfate proteoglycans. Acidic and basic fibroblasts growth factor (FGF) also bound to chick ECM. When ECM was incubated with a protease associated with the enzyme AChE (AChE-AP), APP and acidic FGF were released intact from the matrix. The AChE-AP was at least 100-fold more potent in releasing APP from ECM than other trypsin-like proteases (trypsin, plasmin, thrombin). The action of the AChE-AP was inhibited by glia-derived nexin (protease nexin I) and by human brain APP at low nanomolar concentrations. These results suggest that in vivo an AChE-AP may cleave ECM proteins to regulate the availability of soluble APP or other factors bound to the ECM."} {"id": "PMID:1279137", "title": "Excitatory amino acid-mediated responses and synaptic potentials in medial pontine reticular formation neurons of the rat in vitro.", "content": "Neurons of the medial pontine reticular formation (mPRF) are involved in the execution of numerous behaviors including initiation of locomotion, eye movements, startle responses, and rapid eye movement sleep phenomena. Approximately half of the afferent projections to mPRF neurons come from within the reticular formation (Shammah-Lagnado et al., 1987). In spite of the importance of reticulo-reticular connections, virtually nothing is known about transmitters mediating these synapses. In order to identify a candidate excitatory neurotransmitter, the actions of excitatory amino acids (EAAs) on the membrane properties of mPRF neurons recorded in rat brainstem slices in vitro were studied. Standard intracellular recording methods, including single-electrode voltage clamp, were used to examine the postsynaptic actions of EAAs. We also tested whether EAA antagonists block EPSPs evoked by stimulation of the contralateral reticular formation in the slices. mPRF neurons responded to both non-NMDA and NMDA agonists. NMDA-induced conductances were voltage dependent and depressed by physiological concentrations of magnesium. Stimulation of the contralateral reticular formation elicited EPSPs that were depressed by the general EAA antagonist kynurenate. Evoked EPSPs were partially depressed by 6,7-dinitroquinoxaline-2,3-dione. The evoked EPSP was further reduced by the NMDA antagonist (+/-)-2-amino-5-phosphonopentanoic acid in some cases. These results suggest that excitatory reticulo-reticular neurotransmission is mediated by an EAA. Both non-NMDA and NMDA receptors contribute to EAA neurotransmission in the mPRF formation and play an integral role in reticular formation function.", "contents": "Excitatory amino acid-mediated responses and synaptic potentials in medial pontine reticular formation neurons of the rat in vitro. Neurons of the medial pontine reticular formation (mPRF) are involved in the execution of numerous behaviors including initiation of locomotion, eye movements, startle responses, and rapid eye movement sleep phenomena. Approximately half of the afferent projections to mPRF neurons come from within the reticular formation (Shammah-Lagnado et al., 1987). In spite of the importance of reticulo-reticular connections, virtually nothing is known about transmitters mediating these synapses. In order to identify a candidate excitatory neurotransmitter, the actions of excitatory amino acids (EAAs) on the membrane properties of mPRF neurons recorded in rat brainstem slices in vitro were studied. Standard intracellular recording methods, including single-electrode voltage clamp, were used to examine the postsynaptic actions of EAAs. We also tested whether EAA antagonists block EPSPs evoked by stimulation of the contralateral reticular formation in the slices. mPRF neurons responded to both non-NMDA and NMDA agonists. NMDA-induced conductances were voltage dependent and depressed by physiological concentrations of magnesium. Stimulation of the contralateral reticular formation elicited EPSPs that were depressed by the general EAA antagonist kynurenate. Evoked EPSPs were partially depressed by 6,7-dinitroquinoxaline-2,3-dione. The evoked EPSP was further reduced by the NMDA antagonist (+/-)-2-amino-5-phosphonopentanoic acid in some cases. These results suggest that excitatory reticulo-reticular neurotransmission is mediated by an EAA. Both non-NMDA and NMDA receptors contribute to EAA neurotransmission in the mPRF formation and play an integral role in reticular formation function."} {"id": "PMID:1279138", "title": "Influence of mesostriatal afferents on the development and transmitter regulation of intrastriatal grafts derived from embryonic striatal primordia.", "content": "Embryonic striatal grafts develop a modular organization in which patches of tissue enriched in many transmitter substances characteristic of striatum (P regions) are embedded in surrounds (NP regions) expressing only low levels of these substances. Catecholaminergic fibers from the host brain, identified by their expression of tyrosine hydroxylase (TH), grow into such grafts and selectively terminate in the striatum-like P regions. This terminal pattern suggests that cell-cell affinities between neurons of the substantia nigra and striatum may play a role either in the aggregation of the striatal cells into P regions, or in the targeting of the TH-positive fibers to the cell clusters. In the present study, we tested the first of these possibilities. Striatal grafts derived from embryonic day 15 striatal primordia were implanted into the ibotenate-damaged host striatum of rats previously treated with 6-hydroxydopamine (6-OHDA) to destroy TH-containing dopaminergic nigrostriatal afferents. The 6-OHDA lesions that eliminated nearly all TH-like immunostaining in the host striatum also resulted in disappearance of nearly all TH-positive fibers in the grafts. In this dopamine-depleted environment, the grafts nevertheless developed a clear modular organization. They contained striatum-like patches with neurons expressing many of the neurochemicals characteristic of striatum (ACh, ChAT, calbindin-D28KD, met-enkephalin, and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein-32,000 or DARPP-32), and these patches were surrounded by graft tissue expressing few of these striatal markers. These observations suggest that the ingrowth of TH-positive fibers from the host is not obligatory for the sorting out of striatal from nonstriatal cells during the formation of P regions in embryonic striatal grafts. Despite the fact that dopaminergic denervation of the host striatum did not disrupt either the aggregation of grafted cells into P regions or the acquisition of striatal neurochemical phenotypes by cells in the P regions, there were clear differences between the staining patterns of these grafts and grafts placed into dopamine-innervated striatum. Most striking was a sharp increase of met-enkephalin-like immunostaining in the P zones of the denervated grafts. Upregulation of met-enkephalin is known to occur in the dopamine-depleted mature striatum, and was observed in the parts of host striatum surrounding the grafts on the side ipsilateral to the 6-OHDA lesions. This result suggests that functional interactions between dopaminergic and enkephalinergic systems can occur in the striatal circuits reconstructed by embryonic striatal grafting. More generally, our results suggest that TH-containing afferents from the host striatum, though not required for induction and maintenance of striatal phenotypy in striatal grafts, can chronically regulate neurotransmitter/neuromodulator expression in neurons of the striatum-like P zones in a manner similar to that found for the normal striatum.", "contents": "Influence of mesostriatal afferents on the development and transmitter regulation of intrastriatal grafts derived from embryonic striatal primordia. Embryonic striatal grafts develop a modular organization in which patches of tissue enriched in many transmitter substances characteristic of striatum (P regions) are embedded in surrounds (NP regions) expressing only low levels of these substances. Catecholaminergic fibers from the host brain, identified by their expression of tyrosine hydroxylase (TH), grow into such grafts and selectively terminate in the striatum-like P regions. This terminal pattern suggests that cell-cell affinities between neurons of the substantia nigra and striatum may play a role either in the aggregation of the striatal cells into P regions, or in the targeting of the TH-positive fibers to the cell clusters. In the present study, we tested the first of these possibilities. Striatal grafts derived from embryonic day 15 striatal primordia were implanted into the ibotenate-damaged host striatum of rats previously treated with 6-hydroxydopamine (6-OHDA) to destroy TH-containing dopaminergic nigrostriatal afferents. The 6-OHDA lesions that eliminated nearly all TH-like immunostaining in the host striatum also resulted in disappearance of nearly all TH-positive fibers in the grafts. In this dopamine-depleted environment, the grafts nevertheless developed a clear modular organization. They contained striatum-like patches with neurons expressing many of the neurochemicals characteristic of striatum (ACh, ChAT, calbindin-D28KD, met-enkephalin, and dopamine- and adenosine 3':5'-monophosphate-regulated phosphoprotein-32,000 or DARPP-32), and these patches were surrounded by graft tissue expressing few of these striatal markers. These observations suggest that the ingrowth of TH-positive fibers from the host is not obligatory for the sorting out of striatal from nonstriatal cells during the formation of P regions in embryonic striatal grafts. Despite the fact that dopaminergic denervation of the host striatum did not disrupt either the aggregation of grafted cells into P regions or the acquisition of striatal neurochemical phenotypes by cells in the P regions, there were clear differences between the staining patterns of these grafts and grafts placed into dopamine-innervated striatum. Most striking was a sharp increase of met-enkephalin-like immunostaining in the P zones of the denervated grafts. Upregulation of met-enkephalin is known to occur in the dopamine-depleted mature striatum, and was observed in the parts of host striatum surrounding the grafts on the side ipsilateral to the 6-OHDA lesions. This result suggests that functional interactions between dopaminergic and enkephalinergic systems can occur in the striatal circuits reconstructed by embryonic striatal grafting. More generally, our results suggest that TH-containing afferents from the host striatum, though not required for induction and maintenance of striatal phenotypy in striatal grafts, can chronically regulate neurotransmitter/neuromodulator expression in neurons of the striatum-like P zones in a manner similar to that found for the normal striatum."} {"id": "PMID:1279139", "title": "Distributed but convergent ordering of corticostriatal projections: analysis of the frontal eye field and the supplementary eye field in the macaque monkey.", "content": "The degree of parallel processing in frontal cortex-basal ganglia circuits is a central and debated issue in research on the basal ganglia. To approach this issue directly, we analyzed and compared the corticostriatal projections of two principal oculomotor areas of the frontal lobes, the frontal eye field (FEF) and the supplementary eye field (SEF). We first identified cortical regions within or adjacent to each eye field by microstimulation in macaque monkeys and then injected each site with either 35S-methionine or WGA-HRP conjugate. We analyzed the corticostriatal projections and also the interconnections of the pairs of cortical areas. We observed major convergence of the projections of the FEF and the SEF within the striatum, principally in the caudate nucleus. In cross sections through the striatum, both projections were broken into a series of discontinuous input zones that seemed to be part of complex three-dimensional labyrinths. Where the FEF and SEF projection fields were both present, they overlapped patch for patch. Thus, both inputs were dispersed within the striatum but converged with one another. Striatal afferents from cortex adjacent to the FEF and the SEF did not show convergence with SEF and FEF inputs, but did, in part, converge with one another. For all pairs of cortical areas tested, the degree of overlap in the corticostriatal projections appeared to be directly correlated with the degree of cortical interconnectivity of the areas injected. All of the corticostriatal fiber projections observed primarily avoided immunohistochemically identified striosomes. We conclude that there is convergence of oculomotor information from two distinct regions of the frontal cortex to the striatal matrix, which is known to project into pallidonigral circuits including the striatonigrocollicular pathway of the saccadic eye movement system. Furthermore, functionally distinct premotor areas near the oculomotor fields often systematically projected to striatal zones adjacent to oculomotor field projections, suggesting an anatomical basis for potential interaction of these inputs within the striatum. We propose that parallel processing is not the exclusive principle of organization of forebrain circuits associated with the basal ganglia. Rather, patterns of both convergence and divergence are present and are likely to depend on multiple functional and developmental constraints.", "contents": "Distributed but convergent ordering of corticostriatal projections: analysis of the frontal eye field and the supplementary eye field in the macaque monkey. The degree of parallel processing in frontal cortex-basal ganglia circuits is a central and debated issue in research on the basal ganglia. To approach this issue directly, we analyzed and compared the corticostriatal projections of two principal oculomotor areas of the frontal lobes, the frontal eye field (FEF) and the supplementary eye field (SEF). We first identified cortical regions within or adjacent to each eye field by microstimulation in macaque monkeys and then injected each site with either 35S-methionine or WGA-HRP conjugate. We analyzed the corticostriatal projections and also the interconnections of the pairs of cortical areas. We observed major convergence of the projections of the FEF and the SEF within the striatum, principally in the caudate nucleus. In cross sections through the striatum, both projections were broken into a series of discontinuous input zones that seemed to be part of complex three-dimensional labyrinths. Where the FEF and SEF projection fields were both present, they overlapped patch for patch. Thus, both inputs were dispersed within the striatum but converged with one another. Striatal afferents from cortex adjacent to the FEF and the SEF did not show convergence with SEF and FEF inputs, but did, in part, converge with one another. For all pairs of cortical areas tested, the degree of overlap in the corticostriatal projections appeared to be directly correlated with the degree of cortical interconnectivity of the areas injected. All of the corticostriatal fiber projections observed primarily avoided immunohistochemically identified striosomes. We conclude that there is convergence of oculomotor information from two distinct regions of the frontal cortex to the striatal matrix, which is known to project into pallidonigral circuits including the striatonigrocollicular pathway of the saccadic eye movement system. Furthermore, functionally distinct premotor areas near the oculomotor fields often systematically projected to striatal zones adjacent to oculomotor field projections, suggesting an anatomical basis for potential interaction of these inputs within the striatum. We propose that parallel processing is not the exclusive principle of organization of forebrain circuits associated with the basal ganglia. Rather, patterns of both convergence and divergence are present and are likely to depend on multiple functional and developmental constraints."} {"id": "PMID:1279140", "title": "Diffuse thallium-201-chloride uptake in hypermetabolic bone marrow following treatment with granulocyte stimulating factor.", "content": "Diffuse abnormal uptake of 201Tl-chloride in the bone marrow is described in an AIDS patient with Kaposi's sarcoma who received chemotherapy. The patient developed severe leukopenia that was treated by granulocyte stimulating factor (GCSF). The white blood cells increased from 1500 to 6200 over a period of 4 days. After chemotherapy, the tumor was negative for thallium uptake.", "contents": "Diffuse thallium-201-chloride uptake in hypermetabolic bone marrow following treatment with granulocyte stimulating factor. Diffuse abnormal uptake of 201Tl-chloride in the bone marrow is described in an AIDS patient with Kaposi's sarcoma who received chemotherapy. The patient developed severe leukopenia that was treated by granulocyte stimulating factor (GCSF). The white blood cells increased from 1500 to 6200 over a period of 4 days. After chemotherapy, the tumor was negative for thallium uptake."} {"id": "PMID:1279141", "title": "Cysteine and glycine supplementation modulate the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet.", "content": "Responses to cytokines entail synthesis of substances rich in cysteine and glycine, such as glutathione (GSH), metallothionein and some plasma proteins. To examine the importance of an adequate supply of cysteine and glycine, we fed rats a low protein diet supplemented with L-cysteine and glycine, separately or in combination, or L-alanine, or a high protein diet for 1 wk before injection with tumor necrosis factor alpha (TNF) or saline. The high protein diet-fed group had greater liver weight and zinc and GSH concentrations after TNF than the group fed the low protein diet supplemented with alanine. Glycine and cysteine supplementation resulted in greater liver weight after TNF treatment than did alanine supplementation. Cysteine supplementation had a similar influence on GSH concentration. Ceruloplasmin, alpha-2-macroglobulin and alpha-1-acid glycoprotein were higher in TNF-treated rats than in saline controls in each dietary group. However, feeding supplementary glycine and cysteine and the high protein diet often resulted in different values than seen in animals fed the low protein diet supplemented with alanine. Paradoxically, lower ceruloplasmin concentrations were observed in animals fed the former diets than in those fed the latter. alpha-2-Macroglobulin concentration was lower in all animals fed low protein diets than in those fed the high protein diet. alpha-1-Acid glycoprotein was lowest in groups fed cysteine-supplemented diets and highest in the glycine-supplemented group.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Cysteine and glycine supplementation modulate the metabolic response to tumor necrosis factor alpha in rats fed a low protein diet. Responses to cytokines entail synthesis of substances rich in cysteine and glycine, such as glutathione (GSH), metallothionein and some plasma proteins. To examine the importance of an adequate supply of cysteine and glycine, we fed rats a low protein diet supplemented with L-cysteine and glycine, separately or in combination, or L-alanine, or a high protein diet for 1 wk before injection with tumor necrosis factor alpha (TNF) or saline. The high protein diet-fed group had greater liver weight and zinc and GSH concentrations after TNF than the group fed the low protein diet supplemented with alanine. Glycine and cysteine supplementation resulted in greater liver weight after TNF treatment than did alanine supplementation. Cysteine supplementation had a similar influence on GSH concentration. Ceruloplasmin, alpha-2-macroglobulin and alpha-1-acid glycoprotein were higher in TNF-treated rats than in saline controls in each dietary group. However, feeding supplementary glycine and cysteine and the high protein diet often resulted in different values than seen in animals fed the low protein diet supplemented with alanine. Paradoxically, lower ceruloplasmin concentrations were observed in animals fed the former diets than in those fed the latter. alpha-2-Macroglobulin concentration was lower in all animals fed low protein diets than in those fed the high protein diet. alpha-1-Acid glycoprotein was lowest in groups fed cysteine-supplemented diets and highest in the glycine-supplemented group.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279142", "title": "Prenatal protein malnutrition in rats enhances serotonin release from hippocampus.", "content": "The effect of prenatal protein malnutrition on central serotonin metabolism was assessed in 220- to 240-d-old male rats. The malnourished rats (denoted 6,25 group) were males born to dams fed a 6% casein diet during pregnancy and fostered at birth to dams fed a control (25% casein) diet. They were compared with males born to dams fed 25% casein diet. Tissue concentrations of serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, L-tryptophan and catecholamines in the hippocampal formation in the 6,25 group were similar to those of well-fed controls (25,25 group). However, a twofold greater basal serotonin efflux from hippocampal slices of 6,25 rats compared with slices from 25,25 rats was observed during a 20-min incubation period. Hippocampal [3H]paroxetine binding indicated that there was no alteration of apparent maximal binding and affinity of the serotonin transporter in the 6,25 rats. In addition, there was no difference in serotonin receptor binding in hippocampal membranes from 6,25 and 25,25 rats. The results indicate that prenatal protein malnutrition causes selective changes in central serotonin metabolism.", "contents": "Prenatal protein malnutrition in rats enhances serotonin release from hippocampus. The effect of prenatal protein malnutrition on central serotonin metabolism was assessed in 220- to 240-d-old male rats. The malnourished rats (denoted 6,25 group) were males born to dams fed a 6% casein diet during pregnancy and fostered at birth to dams fed a control (25% casein) diet. They were compared with males born to dams fed 25% casein diet. Tissue concentrations of serotonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophan, L-tryptophan and catecholamines in the hippocampal formation in the 6,25 group were similar to those of well-fed controls (25,25 group). However, a twofold greater basal serotonin efflux from hippocampal slices of 6,25 rats compared with slices from 25,25 rats was observed during a 20-min incubation period. Hippocampal [3H]paroxetine binding indicated that there was no alteration of apparent maximal binding and affinity of the serotonin transporter in the 6,25 rats. In addition, there was no difference in serotonin receptor binding in hippocampal membranes from 6,25 and 25,25 rats. The results indicate that prenatal protein malnutrition causes selective changes in central serotonin metabolism."} {"id": "PMID:1279143", "title": "Expression of retinoic acid nuclear receptors and tissue transglutaminase is altered in various tissues of rats fed a vitamin A-deficient diet.", "content": "The effects of vitamin A nutritional status on the levels of expression of retinoic acid nuclear receptors (RAR), and the retinoic acid-responsive gene, tissue transglutaminase, were determined in rats. Weanling male Sprague-Dawley rats fed a vitamin A-deficient diet for approximately 7 wk developed vitamin A deficiency, as confirmed by the depletion of liver retinol and retinyl palmitate. Controls were fed the same diet supplemented with 24 mg/kg retinyl acetate. The levels of expression of RAR beta mRNA were approximately 80% lower in bladder, brain, liver, lung and trachea and those of RAR gamma mRNA were approximately 50% lower in bladder, lung and trachea of rats fed the vitamin A-deficient diet than in controls. The levels of expression of RAR alpha mRNA were approximately 90% lower in brain and approximately 30% greater in liver, kidney, intestine and lung of rats fed the vitamin A-deficient diet. Vitamin A deficiency also resulted in reduced expression of tissue transglutaminase in the bladder, lungs and trachea, which paralleled the effects observed for RAR beta and RAR gamma. When vitamin A-deficient rats were subsequently fed a retinol-deficient diet supplemented with retinoic acid for 4 wk, the expression of RAR (beta and gamma) and tissue transglutaminase returned to the control levels. These results indicate that vitamin A nutritional status in rats influences the expression of both RAR and tissue transglutaminase in certain tissues.", "contents": "Expression of retinoic acid nuclear receptors and tissue transglutaminase is altered in various tissues of rats fed a vitamin A-deficient diet. The effects of vitamin A nutritional status on the levels of expression of retinoic acid nuclear receptors (RAR), and the retinoic acid-responsive gene, tissue transglutaminase, were determined in rats. Weanling male Sprague-Dawley rats fed a vitamin A-deficient diet for approximately 7 wk developed vitamin A deficiency, as confirmed by the depletion of liver retinol and retinyl palmitate. Controls were fed the same diet supplemented with 24 mg/kg retinyl acetate. The levels of expression of RAR beta mRNA were approximately 80% lower in bladder, brain, liver, lung and trachea and those of RAR gamma mRNA were approximately 50% lower in bladder, lung and trachea of rats fed the vitamin A-deficient diet than in controls. The levels of expression of RAR alpha mRNA were approximately 90% lower in brain and approximately 30% greater in liver, kidney, intestine and lung of rats fed the vitamin A-deficient diet. Vitamin A deficiency also resulted in reduced expression of tissue transglutaminase in the bladder, lungs and trachea, which paralleled the effects observed for RAR beta and RAR gamma. When vitamin A-deficient rats were subsequently fed a retinol-deficient diet supplemented with retinoic acid for 4 wk, the expression of RAR (beta and gamma) and tissue transglutaminase returned to the control levels. These results indicate that vitamin A nutritional status in rats influences the expression of both RAR and tissue transglutaminase in certain tissues."} {"id": "PMID:1279144", "title": "The quality and quantity of dietary protein affect brain protein synthesis in rats.", "content": "The influence of the amino acid supply in diets with different quality and quantity of protein on the rate of protein synthesis in the brain was investigated. Amino acid concentrations in serum and brain altered in accordance with the amino acid levels of the diets, with the exception of some amino acids such as aspartic acid, glutamic acid, glycine and threonine. When rats were fed various levels of dietary casein (0, 5 and 20%), the aggregation of ribosomes increased and the fractional rate of protein synthesis tended to increase with the increase in dietary protein. When rats were fed a 20% casein diet, greater aggregation of brain ribosomes and protein synthesis rate were observed compared with those in rats fed 20% wheat gluten or gelatin diets. The RNA activity was related to the degree of the aggregation of brain ribosomes and the fractional rate of protein synthesis.", "contents": "The quality and quantity of dietary protein affect brain protein synthesis in rats. The influence of the amino acid supply in diets with different quality and quantity of protein on the rate of protein synthesis in the brain was investigated. Amino acid concentrations in serum and brain altered in accordance with the amino acid levels of the diets, with the exception of some amino acids such as aspartic acid, glutamic acid, glycine and threonine. When rats were fed various levels of dietary casein (0, 5 and 20%), the aggregation of ribosomes increased and the fractional rate of protein synthesis tended to increase with the increase in dietary protein. When rats were fed a 20% casein diet, greater aggregation of brain ribosomes and protein synthesis rate were observed compared with those in rats fed 20% wheat gluten or gelatin diets. The RNA activity was related to the degree of the aggregation of brain ribosomes and the fractional rate of protein synthesis."} {"id": "PMID:1279153", "title": "Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection.", "content": "Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT.", "contents": "Combination treatment with azidothymidine and granulocyte colony-stimulating factor in children with human immunodeficiency virus infection. Bone marrow suppression is the major dose-limiting toxic effect of zidovudine (azidothymidine; AZT) in children with human immunodeficiency virus infection. We evaluated the effect of subcutaneously administered granulocyte colony-stimulating factor (G-CSF) in pediatric patients whose absolute neutrophil count was less than 0.8 x 10(9)/L during AZT therapy despite dosage reductions to 120 mg/m2 every 6 hours. Nineteen patients between 6 months and 20 years of age were treated with AZT and G-CSF and monitored for 2 to 12 months. All had previously shown improvement while receiving AZT but had required dosage reduction or discontinuation. By using a sliding dosing schedule of G-CSF, we attempted to maintain the absolute neutrophil count between 1.5 and 5.0 x 10(9)/L. Administration of G-CSF resulted in a significant increase in the median leukocyte count (2.0 x 10(9)/L to 4.14 x 10(9)/L; p = 0.004), and the median absolute neutrophil count (1.02 x 10(9)/L to 2.96 x 10(9)/L; p = 0.0006). G-CSF was well tolerated, but mild thrombocytopenia developed in nine children. Administration of G-CSF and AZT was discontinued in two patients because of continuing neutropenia. With doses of G-CSF ranging from 1 to 20 micrograms/kg per day, 17 of 19 patients were able to tolerate AZT at a dose of 120 to 180 mg/m2 every 6 hours. We conclude that G-CSF therapy enables patients who have had AZT-related neutropenia to receive therapeutic doses of AZT."} {"id": "PMID:1279154", "title": "Granulocyte-colony stimulating factor facilitates the restoration of resistance to opportunistic fungi in leukopenic mice.", "content": "Administration of recombinant human granulocyte-colony stimulating factor (G-CSF), which induces hemopoietic precursor cells to proliferate and differentiate into neutrophils, protected leukopenic mice infected with opportunistic fungi. Mice were injected with cyclophosphamide and were then subcutaneously (s.c.) or intravenously (i.v.) administered 15-120 micrograms G-CSF kg-1 day-1 for 3 days. The number of peripheral blood neutrophils in the G-CSF treated mice was significantly increased 48 h after G-CSF administration. All leukopenic mice infected with either Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus were significantly protected by treatment with the G-CSF. Moreover, G-CSF treatment caused a decrease in the number of viable yeasts in kidneys of Candida infected mice. These data suggest that prophylactic therapy with G-CSF may be useful against fungal infections in an immunocompromised host.", "contents": "Granulocyte-colony stimulating factor facilitates the restoration of resistance to opportunistic fungi in leukopenic mice. Administration of recombinant human granulocyte-colony stimulating factor (G-CSF), which induces hemopoietic precursor cells to proliferate and differentiate into neutrophils, protected leukopenic mice infected with opportunistic fungi. Mice were injected with cyclophosphamide and were then subcutaneously (s.c.) or intravenously (i.v.) administered 15-120 micrograms G-CSF kg-1 day-1 for 3 days. The number of peripheral blood neutrophils in the G-CSF treated mice was significantly increased 48 h after G-CSF administration. All leukopenic mice infected with either Candida albicans, Cryptococcus neoformans or Aspergillus fumigatus were significantly protected by treatment with the G-CSF. Moreover, G-CSF treatment caused a decrease in the number of viable yeasts in kidneys of Candida infected mice. These data suggest that prophylactic therapy with G-CSF may be useful against fungal infections in an immunocompromised host."} {"id": "PMID:1279155", "title": "Demonstration of the receptor-mediated hepatic uptake of dextran in mice.", "content": "To establish a rationale of designing a drug targeting system using dextran conjugation, the disposition behaviour of dextran itself was investigated in mice. At a high dose (100 mg kg-1), [14C]dextran was retained in the blood circulation for a considerably long period. However, [14C]dextran rapidly disappeared from the plasma and accumulated in the liver (up to 60% of dose in 1 h) after a dose of 1 mg kg-1. Cellular localization of [14C]dextran in the liver following intravenous administration was examined and the contribution of parenchymal cells was demonstrated as well as the case of galactosylated bovine serum albumin (Gal-BSA). Pharmacokinetic analysis based on a physiological model including Michaelis-Menten type uptake mechanisms revealed that the Michaelis constant Km,l of [14C]dextran was 100 times greater than that of Gal-BSA. Coadministration of Gal-BSA delayed the hepatic uptake of [14C]dextran and the simulation based on the physiological model suggested that [14C]dextran was taken up by the same mechanism as Gal-BSA. These results suggested that dextran conjugation of a drug might lead to its undesirable accumulation in the liver at a low dose and an appropriate modification of dextran, such as carboxymethylation, would be required in such cases.", "contents": "Demonstration of the receptor-mediated hepatic uptake of dextran in mice. To establish a rationale of designing a drug targeting system using dextran conjugation, the disposition behaviour of dextran itself was investigated in mice. At a high dose (100 mg kg-1), [14C]dextran was retained in the blood circulation for a considerably long period. However, [14C]dextran rapidly disappeared from the plasma and accumulated in the liver (up to 60% of dose in 1 h) after a dose of 1 mg kg-1. Cellular localization of [14C]dextran in the liver following intravenous administration was examined and the contribution of parenchymal cells was demonstrated as well as the case of galactosylated bovine serum albumin (Gal-BSA). Pharmacokinetic analysis based on a physiological model including Michaelis-Menten type uptake mechanisms revealed that the Michaelis constant Km,l of [14C]dextran was 100 times greater than that of Gal-BSA. Coadministration of Gal-BSA delayed the hepatic uptake of [14C]dextran and the simulation based on the physiological model suggested that [14C]dextran was taken up by the same mechanism as Gal-BSA. These results suggested that dextran conjugation of a drug might lead to its undesirable accumulation in the liver at a low dose and an appropriate modification of dextran, such as carboxymethylation, would be required in such cases."} {"id": "PMID:1279156", "title": "A comparison of glycine, sarcosine, N,N-dimethylglycine, glycinebetaine and N-modified betaines as liposome cryoprotectants.", "content": "Glycinebetaine has previously been shown to be effective at reducing leakage from liposomes which are frozen then thawed. This study involved the preparation of a series of N-modified betaines and the comparison of their cryoprotective activities with those of glycine, sarcosine, N,N-dimethylglycine and glycinebetaine. All the compounds investigated, with the exception of (dimethyloctylammonio)acetate, reduced the degree of leakage, after freezing and thawing, with additive concentrations up to 0.6 M. Reducing the degree of N-terminal methylation of glycinebetaine appeared to increase the leakage from liposomes at additive concentrations between 0.2 and 0.6 M. (Dimethylethylammonio)acetate, (dimethylisopropylammonio)acetate and (N,N,N',N'-tetramethylethylenediammonio)-N,N'-diacetate appeared to be no more effective than glycinebetaine, whereas improved protection was afforded by (triethylammonio)acetate and (diethylmethylammonio)acetate at most concentrations. This study demonstrates that the cryoprotective activity of glycinebetaine may be improved with modifications to the N-terminal.", "contents": "A comparison of glycine, sarcosine, N,N-dimethylglycine, glycinebetaine and N-modified betaines as liposome cryoprotectants. Glycinebetaine has previously been shown to be effective at reducing leakage from liposomes which are frozen then thawed. This study involved the preparation of a series of N-modified betaines and the comparison of their cryoprotective activities with those of glycine, sarcosine, N,N-dimethylglycine and glycinebetaine. All the compounds investigated, with the exception of (dimethyloctylammonio)acetate, reduced the degree of leakage, after freezing and thawing, with additive concentrations up to 0.6 M. Reducing the degree of N-terminal methylation of glycinebetaine appeared to increase the leakage from liposomes at additive concentrations between 0.2 and 0.6 M. (Dimethylethylammonio)acetate, (dimethylisopropylammonio)acetate and (N,N,N',N'-tetramethylethylenediammonio)-N,N'-diacetate appeared to be no more effective than glycinebetaine, whereas improved protection was afforded by (triethylammonio)acetate and (diethylmethylammonio)acetate at most concentrations. This study demonstrates that the cryoprotective activity of glycinebetaine may be improved with modifications to the N-terminal."} {"id": "PMID:1279157", "title": "Effect of ryanodine on histamine release from rat peritoneal mast cells induced by anti-IgE.", "content": "Ryanodine strongly inhibited histamine release from rat peritoneal mast cells induced by anti-IgE. Ryanodine also inhibited Ca(2+)-mobilization from the intracellular Ca(2+)-store as well as histamine release in mast cells activated by anti-IgE. These results suggest that the effect of ryanodine on histamine release from rat mast cells might be due to the inhibition of Ca2+ release from the intracellular Ca2+ store.", "contents": "Effect of ryanodine on histamine release from rat peritoneal mast cells induced by anti-IgE. Ryanodine strongly inhibited histamine release from rat peritoneal mast cells induced by anti-IgE. Ryanodine also inhibited Ca(2+)-mobilization from the intracellular Ca(2+)-store as well as histamine release in mast cells activated by anti-IgE. These results suggest that the effect of ryanodine on histamine release from rat mast cells might be due to the inhibition of Ca2+ release from the intracellular Ca2+ store."} {"id": "PMID:1279158", "title": "Molecular-weight-dependent pharmacokinetics of fluorescein-labeled dextrans in rats.", "content": "The dependency of the pharmacokinetics of fluorescein-labeled dextrans on M(r) was studied in adult Sprague-Dawley rats. Single intravenous doses (5 mg/kg) of the dextrans with M(r) of 4000, 20,000, 40,000, 70,000, or 150,000 and single oral doses (50 mg/kg) of the dextrans with M(r) of 4000, 20,000, or 40,000 were administered to different groups of rats. A specific and sensitive high-performance, size-exclusion chromatographic method was used to measure the concentrations of the dextrans in serial serum and urine samples, and the relevant kinetic parameters were calculated. After intravenous administration, the profiles of the concentration of dextran in serum versus time for all the studied dextrans exhibited an apparent biexponential decline, with all the calculated kinetic parameters being dependent on M(r). However, the degree of dependency varied for different parameters. Among the calculated kinetic parameters, renal clearance and volume of distribution values were affected the most and least, respectively, by the differences in M(r). Furthermore, we observed a clear separation between the labeled dextrans with M(r) less than or equal to 20,000 and those with M(r) greater than or equal to 40,000 with respect to their concentrations in serum and kinetic parameters. After oral administration, the dextrans could not be detected in serum, and on the basis of urine data, only negligible amounts of the macromolecules were absorbed into the systemic circulation (less than 0.4% of the dose). The data presented here may be used in the future design of microvascular and drug delivery studies with dextrans.", "contents": "Molecular-weight-dependent pharmacokinetics of fluorescein-labeled dextrans in rats. The dependency of the pharmacokinetics of fluorescein-labeled dextrans on M(r) was studied in adult Sprague-Dawley rats. Single intravenous doses (5 mg/kg) of the dextrans with M(r) of 4000, 20,000, 40,000, 70,000, or 150,000 and single oral doses (50 mg/kg) of the dextrans with M(r) of 4000, 20,000, or 40,000 were administered to different groups of rats. A specific and sensitive high-performance, size-exclusion chromatographic method was used to measure the concentrations of the dextrans in serial serum and urine samples, and the relevant kinetic parameters were calculated. After intravenous administration, the profiles of the concentration of dextran in serum versus time for all the studied dextrans exhibited an apparent biexponential decline, with all the calculated kinetic parameters being dependent on M(r). However, the degree of dependency varied for different parameters. Among the calculated kinetic parameters, renal clearance and volume of distribution values were affected the most and least, respectively, by the differences in M(r). Furthermore, we observed a clear separation between the labeled dextrans with M(r) less than or equal to 20,000 and those with M(r) greater than or equal to 40,000 with respect to their concentrations in serum and kinetic parameters. After oral administration, the dextrans could not be detected in serum, and on the basis of urine data, only negligible amounts of the macromolecules were absorbed into the systemic circulation (less than 0.4% of the dose). The data presented here may be used in the future design of microvascular and drug delivery studies with dextrans."} {"id": "PMID:1279159", "title": "Differential effects of somatostatin and prostaglandins on gastric histamine release to pentagastrin.", "content": "The effects of gastric acid antisecretory agents prostaglandins E2, I2 (PGE2, PGI2) and somatostatin on pentagastrin-stimulated gastric histamine and N tau-methyl histamine secretory rates were examined in anesthetized mixed breed dogs. We infused two gastric acid antisecretory doses of PGE2 and PGI2 to test the effect of prostaglandins on pentagastrin-stimulated gastric histamine release. Neither dose of PGE2 and PGI2 had an effect on pentagastrin-stimulated histamine and N tau-methyl histamine release, even though the prostaglandins caused marked gastric vasodilation. In addition, the infusion of the higher dose of PGE2 and PGI2 alone had no effect on histamine secretory rates. In contrast, somatostatin inhibited both pentagastrin-stimulated gastric histamine release by approximately 95% as well as basal histamine release by approximately 60%. Somatostatin also inhibited the pentagastrin-stimulated N tau-methyl histamine secretory rates. The results indicate that neither PGE2 nor PGI2 at antisecretory doses affect pentagastrin-stimulated gastric histamine release, but somatostatin has a very potent inhibitory effect in that regard. Our data suggest that the mechanisms by which prostaglandins and somatostatin affect gastric acid secretion may be diverse.", "contents": "Differential effects of somatostatin and prostaglandins on gastric histamine release to pentagastrin. The effects of gastric acid antisecretory agents prostaglandins E2, I2 (PGE2, PGI2) and somatostatin on pentagastrin-stimulated gastric histamine and N tau-methyl histamine secretory rates were examined in anesthetized mixed breed dogs. We infused two gastric acid antisecretory doses of PGE2 and PGI2 to test the effect of prostaglandins on pentagastrin-stimulated gastric histamine release. Neither dose of PGE2 and PGI2 had an effect on pentagastrin-stimulated histamine and N tau-methyl histamine release, even though the prostaglandins caused marked gastric vasodilation. In addition, the infusion of the higher dose of PGE2 and PGI2 alone had no effect on histamine secretory rates. In contrast, somatostatin inhibited both pentagastrin-stimulated gastric histamine release by approximately 95% as well as basal histamine release by approximately 60%. Somatostatin also inhibited the pentagastrin-stimulated N tau-methyl histamine secretory rates. The results indicate that neither PGE2 nor PGI2 at antisecretory doses affect pentagastrin-stimulated gastric histamine release, but somatostatin has a very potent inhibitory effect in that regard. Our data suggest that the mechanisms by which prostaglandins and somatostatin affect gastric acid secretion may be diverse."} {"id": "PMID:1279160", "title": "Activation of an epithelial neurokinin NK-1 receptor induces relaxation of rat trachea through release of prostaglandin E2.", "content": "We studied the type of neurokinin (NK) receptor involved in the epithelium-dependent substance P (SP)-induced relaxation of rat trachea precontracted with serotonin (5-HT). We first compared the relaxant effects of different agonists to the three NK receptors on rat trachea in the presence (E+) and absence (E-) of the epithelium. The three agonists to the NK-1 receptor, SP, SP-O-methylester and [beta Ala4, Sar9, Met(O2)] SP(4-11), at a concentration of 1 microM induced a relaxation of 40 +/- 5, 33 +/- 4 and 31 +/- 6%, respectively in E+ segments. They had weak and nonsignificant effects in E- segments. In addition, (+/-)CP-96,345 (1 microM), the NK-1-selective non-peptide antagonist, inhibited the SP-induced relaxation by 45%. Conversely, the three NK-2 receptor agonists, NKA, NKA(4-10) and [Nle10]NKA(4-10), and the two NK-3 receptor agonists, neurokinin B (NKB) and [MePhe7]NKB(4-10), had no effect on E+ or E- tracheal segments. The N-terminal SP fragment SP(1-9) was also inactive. These results suggest that SP-induced relaxation is mediated through activation of epithelial NK-1 receptors. Preincubation with the cyclooxygenase inhibitor, indomethacin (2.8 microM), abrogated the relaxant effect of the three NK-1 receptor agonists on E+ tracheas. We measured in additional experiments prostaglandin E2 (PGE2), PGF2 alpha, 6-keto PGF1 alpha and thromboxane B2. SP (1 microM) induced a 6.1-fold increase in PGE2 production (from 13 pg after 5-HT to 78 pg) in E+ segments, whereas only a 1.5-fold increase occurred in E- preparations.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Activation of an epithelial neurokinin NK-1 receptor induces relaxation of rat trachea through release of prostaglandin E2. We studied the type of neurokinin (NK) receptor involved in the epithelium-dependent substance P (SP)-induced relaxation of rat trachea precontracted with serotonin (5-HT). We first compared the relaxant effects of different agonists to the three NK receptors on rat trachea in the presence (E+) and absence (E-) of the epithelium. The three agonists to the NK-1 receptor, SP, SP-O-methylester and [beta Ala4, Sar9, Met(O2)] SP(4-11), at a concentration of 1 microM induced a relaxation of 40 +/- 5, 33 +/- 4 and 31 +/- 6%, respectively in E+ segments. They had weak and nonsignificant effects in E- segments. In addition, (+/-)CP-96,345 (1 microM), the NK-1-selective non-peptide antagonist, inhibited the SP-induced relaxation by 45%. Conversely, the three NK-2 receptor agonists, NKA, NKA(4-10) and [Nle10]NKA(4-10), and the two NK-3 receptor agonists, neurokinin B (NKB) and [MePhe7]NKB(4-10), had no effect on E+ or E- tracheal segments. The N-terminal SP fragment SP(1-9) was also inactive. These results suggest that SP-induced relaxation is mediated through activation of epithelial NK-1 receptors. Preincubation with the cyclooxygenase inhibitor, indomethacin (2.8 microM), abrogated the relaxant effect of the three NK-1 receptor agonists on E+ tracheas. We measured in additional experiments prostaglandin E2 (PGE2), PGF2 alpha, 6-keto PGF1 alpha and thromboxane B2. SP (1 microM) induced a 6.1-fold increase in PGE2 production (from 13 pg after 5-HT to 78 pg) in E+ segments, whereas only a 1.5-fold increase occurred in E- preparations.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279161", "title": "Permeability and Mg2+ blockade of histamine-operated cation channel in endothelial cells of rat intrapulmonary artery.", "content": "1. In the cell-attached and inside-out patch-clamp experiments using undispersed endothelial cells of the rat intrapulmonary artery, the majority of channels were cation selective. 2. Under physiological ionic conditions, the I-V relationship for the inward currents fell to -80 mV and the slope conductance was 22.5 pS. There was an inward rectification and the outward currents were smaller than the inward currents. 3. Under symmetric high-K+ conditions, the slope conductance for the inward currents was 26.4 pS and the inward rectification was observed when the high-K+ solution contained 1 mM-Mg2+. The channel activity was weakly voltage dependent at negative membrane potentials, while it was much enhanced at positive potentials. 4. The channel activity did not depend on intracellular Ca2+ concentrations. 5. Mg2+ was not only impermeant, it also blocked this channel in a voltage-dependent manner and rectifications appeared in the I-V relationship. Mg2+ blocked the channel from both sides of the membrane. 6. Ca2+ permeated this channel and the permeability ratios calculated from the reversal potentials using the constant-field theory were; PK:PNa:PCa = 1:1:15.7. 7. Histamine but not acetylcholine applied to the pipette activated this channel. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) applied to the intracellular surface of the patch did not mimic the effect of histamine. 8. Thus, in the endothelial cell membrane of the rat intrapulmonary artery, there exists a cation channel which is selective to Ca2+ but also permeable to Na+ and K+. This channel has inward rectifying properties, possibly due to intracellular Mg2+. Histamine, but not acetylcholine, activates this cation channel to elevate endothelial [Ca2+]i.", "contents": "Permeability and Mg2+ blockade of histamine-operated cation channel in endothelial cells of rat intrapulmonary artery. 1. In the cell-attached and inside-out patch-clamp experiments using undispersed endothelial cells of the rat intrapulmonary artery, the majority of channels were cation selective. 2. Under physiological ionic conditions, the I-V relationship for the inward currents fell to -80 mV and the slope conductance was 22.5 pS. There was an inward rectification and the outward currents were smaller than the inward currents. 3. Under symmetric high-K+ conditions, the slope conductance for the inward currents was 26.4 pS and the inward rectification was observed when the high-K+ solution contained 1 mM-Mg2+. The channel activity was weakly voltage dependent at negative membrane potentials, while it was much enhanced at positive potentials. 4. The channel activity did not depend on intracellular Ca2+ concentrations. 5. Mg2+ was not only impermeant, it also blocked this channel in a voltage-dependent manner and rectifications appeared in the I-V relationship. Mg2+ blocked the channel from both sides of the membrane. 6. Ca2+ permeated this channel and the permeability ratios calculated from the reversal potentials using the constant-field theory were; PK:PNa:PCa = 1:1:15.7. 7. Histamine but not acetylcholine applied to the pipette activated this channel. Guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) applied to the intracellular surface of the patch did not mimic the effect of histamine. 8. Thus, in the endothelial cell membrane of the rat intrapulmonary artery, there exists a cation channel which is selective to Ca2+ but also permeable to Na+ and K+. This channel has inward rectifying properties, possibly due to intracellular Mg2+. Histamine, but not acetylcholine, activates this cation channel to elevate endothelial [Ca2+]i."} {"id": "PMID:1279162", "title": "Calcium channel currents in Xenopus oocytes injected with rat skeletal muscle RNA.", "content": "1. Ba2+ currents (IBa) through voltage-dependent Ca2+ channels were studied in Xenopus laevis oocytes injected with heterologous RNA extracted from skeletal muscle (SkM) of young rats, using the two-electrode voltage clamp technique. 2. With 40 or 50 mM-extracellular Ba2+, native oocytes of most frogs displayed IBa between -5 and -20 nA at 0 mV. However, in 'variant' native oocytes of four frogs, IBa exceeded -30 nA and reached up to -100 nA. In oocytes injected with SkM RNA, IBa of up to -250 nA was observed. 3. In SkM RNA-injected oocytes and 'variant' native oocytes, the decay of IBa displayed two kinetic components. The faster component was selectively blocked by 40-100 microM-Ni2+ and thus was termed the Ni(2+)-sensitive IBa. The slower component was Ni2+ resistant, being inhibited only 10-20% by 100-200 microM-Ni2+. The half-activation and the half-inactivation voltages of the Ni(2+)-sensitive IBa were more negative (by 14.5 and 28.7 mV, respectively) than those of the Ni(2+)-resistant IBa. 4. Neither Ni(2+)-sensitive nor Ni(2+)-resistant IBa in native or SkM RNA-injected oocytes were affected by dihydropyridine antagonists nifedipine and (+) PN 200-110 (1-10 microM), by the dihydropyridine agonist (-)Bay K 8644 (0.01-2 microM), or by verapamil below 50 microM. IBa was blocked by diltiazem (half-block at about 500 microM). Thus, the pharmacology of IBa in SkM RNA-injected and in native oocytes was not characteristic of the L-type Ca2+ channel abundant in the skeletal muscle. 5. Destruction of the RNA coding for the channel-forming alpha 1-subunit of the SkM L-type Ca2+ channel using a hybrid arrest method failed to selectively suppress the appearance of either Ni(2+)-sensitive or Ni(2+)-resistant IBa in SkM RNA-injected oocytes. 6. Our results suggest that the appearance of large voltage-dependent Ba2+ currents in SkM RNA-injected oocytes is not due to the expression of the alpha 1-subunit of the SkM L-type Ca2+ channel. The possibility that the expression of a channel-forming subunit of another Ca2+ channel type underlies one of these currents cannot be rejected. However, since the Ba2+ currents in SkM RNA-injected oocytes resemble those observed in native oocytes, we suggest that their appearance may be the result of an enhanced activity of the native Ca2+ channels, possibly due to the expression of the 'auxiliary' subunits of the SkM Ca2+ channel that form complexes with a native alpha 1-subunit.", "contents": "Calcium channel currents in Xenopus oocytes injected with rat skeletal muscle RNA. 1. Ba2+ currents (IBa) through voltage-dependent Ca2+ channels were studied in Xenopus laevis oocytes injected with heterologous RNA extracted from skeletal muscle (SkM) of young rats, using the two-electrode voltage clamp technique. 2. With 40 or 50 mM-extracellular Ba2+, native oocytes of most frogs displayed IBa between -5 and -20 nA at 0 mV. However, in 'variant' native oocytes of four frogs, IBa exceeded -30 nA and reached up to -100 nA. In oocytes injected with SkM RNA, IBa of up to -250 nA was observed. 3. In SkM RNA-injected oocytes and 'variant' native oocytes, the decay of IBa displayed two kinetic components. The faster component was selectively blocked by 40-100 microM-Ni2+ and thus was termed the Ni(2+)-sensitive IBa. The slower component was Ni2+ resistant, being inhibited only 10-20% by 100-200 microM-Ni2+. The half-activation and the half-inactivation voltages of the Ni(2+)-sensitive IBa were more negative (by 14.5 and 28.7 mV, respectively) than those of the Ni(2+)-resistant IBa. 4. Neither Ni(2+)-sensitive nor Ni(2+)-resistant IBa in native or SkM RNA-injected oocytes were affected by dihydropyridine antagonists nifedipine and (+) PN 200-110 (1-10 microM), by the dihydropyridine agonist (-)Bay K 8644 (0.01-2 microM), or by verapamil below 50 microM. IBa was blocked by diltiazem (half-block at about 500 microM). Thus, the pharmacology of IBa in SkM RNA-injected and in native oocytes was not characteristic of the L-type Ca2+ channel abundant in the skeletal muscle. 5. Destruction of the RNA coding for the channel-forming alpha 1-subunit of the SkM L-type Ca2+ channel using a hybrid arrest method failed to selectively suppress the appearance of either Ni(2+)-sensitive or Ni(2+)-resistant IBa in SkM RNA-injected oocytes. 6. Our results suggest that the appearance of large voltage-dependent Ba2+ currents in SkM RNA-injected oocytes is not due to the expression of the alpha 1-subunit of the SkM L-type Ca2+ channel. The possibility that the expression of a channel-forming subunit of another Ca2+ channel type underlies one of these currents cannot be rejected. However, since the Ba2+ currents in SkM RNA-injected oocytes resemble those observed in native oocytes, we suggest that their appearance may be the result of an enhanced activity of the native Ca2+ channels, possibly due to the expression of the 'auxiliary' subunits of the SkM Ca2+ channel that form complexes with a native alpha 1-subunit."} {"id": "PMID:1279163", "title": "Reactivity of monoclonal antibodies 17.13 and 63.12 with 141 oral mucosal lesions.", "content": "We studied the reactivity of monoclonal antibodies (MAbs) 17.13 and 63.12 with normal and diseased human oral mucosa by means of the immunoperoxidase technique. The specimens included: 22 normal oral tissues, 20 benign tumors, 17 lichen planus, 23 focal keratosis and epithelial hyperplasias, 18 proliferative verrucous leukoplakias, 20 dysplasias, and 21 squamous cell carcinomas. In most cases of normal mucosa and benign lesions, MAb 17.13 stained basal epithelial cells only, whereas MAb 63.12 stained all cell layers above the basal cells. In the premalignant and malignant lesions MAb 17.13 stained above the basal cells and MAb 63.12 either stained areas not stained by MAb 17.13 or the staining was absent. Based on the different staining patterns observed, there appears to be a potential value of these new reagents in diagnostic histopathology regarding specimens with equivocal cellular morphology.", "contents": "Reactivity of monoclonal antibodies 17.13 and 63.12 with 141 oral mucosal lesions. We studied the reactivity of monoclonal antibodies (MAbs) 17.13 and 63.12 with normal and diseased human oral mucosa by means of the immunoperoxidase technique. The specimens included: 22 normal oral tissues, 20 benign tumors, 17 lichen planus, 23 focal keratosis and epithelial hyperplasias, 18 proliferative verrucous leukoplakias, 20 dysplasias, and 21 squamous cell carcinomas. In most cases of normal mucosa and benign lesions, MAb 17.13 stained basal epithelial cells only, whereas MAb 63.12 stained all cell layers above the basal cells. In the premalignant and malignant lesions MAb 17.13 stained above the basal cells and MAb 63.12 either stained areas not stained by MAb 17.13 or the staining was absent. Based on the different staining patterns observed, there appears to be a potential value of these new reagents in diagnostic histopathology regarding specimens with equivocal cellular morphology."} {"id": "PMID:1279165", "title": "[Primary mediastinal choriocarcinoma. Apropos of 3 cases].", "content": "We report three cases about the diagnostic imaging features of mediastinal choriocarcinoma and during follow up. Computed tomography proved to be more accurate than plain X ray to show the topography and volume of the mediastinal mass hence providing a better approach for biopsy and surgical ablation of the residual tumoral tissues. However, CT cannot differentiate fibrous tumoral remnants from active malignancies and beta HCG is an important tumoral marker in the follow up.", "contents": "[Primary mediastinal choriocarcinoma. Apropos of 3 cases]. We report three cases about the diagnostic imaging features of mediastinal choriocarcinoma and during follow up. Computed tomography proved to be more accurate than plain X ray to show the topography and volume of the mediastinal mass hence providing a better approach for biopsy and surgical ablation of the residual tumoral tissues. However, CT cannot differentiate fibrous tumoral remnants from active malignancies and beta HCG is an important tumoral marker in the follow up."} {"id": "PMID:1279166", "title": "Amniotic fluid levels of substance P.", "content": "The presence of substance P (SP) in the amniotic fluid (AF) from 88 obstetric patients was determined with a radioimmunoassay. AF was collected from each patient in EDTA-coated tubes. Cross-reactivity of anti-SP antibody with methionine, met-enkephalin, leu-enkephalin, beta-endorphin, eledoisen and physalemin was less than 1%. The SP levels during the midtrimester were not significantly lower than those of late gestation. Data on the late-gestation group were evaluated further as per the clinical problem. The only statistically significant finding was between the diabetics with fetal maturity and the non-diabetic group. This preliminary study identified the presence of SP in AF in mid and late gestation.", "contents": "Amniotic fluid levels of substance P. The presence of substance P (SP) in the amniotic fluid (AF) from 88 obstetric patients was determined with a radioimmunoassay. AF was collected from each patient in EDTA-coated tubes. Cross-reactivity of anti-SP antibody with methionine, met-enkephalin, leu-enkephalin, beta-endorphin, eledoisen and physalemin was less than 1%. The SP levels during the midtrimester were not significantly lower than those of late gestation. Data on the late-gestation group were evaluated further as per the clinical problem. The only statistically significant finding was between the diabetics with fetal maturity and the non-diabetic group. This preliminary study identified the presence of SP in AF in mid and late gestation."} {"id": "PMID:1279167", "title": "The immunoregulation of rheumatoid factor by the CD8 T lymphocyte subset in rheumatoid arthritis.", "content": "Flow cytometric analysis on 81 peripheral blood samples from patients with rheumatoid arthritis (RA) showed that levels of serum IgM rheumatoid factor (RF) were associated with the CD8+ cell level. A significant elevation of natural killer (CD56) cell levels was also observed in RA peripheral blood. Using in vitro antibody production techniques, CD8+ cells from patients with RA appeared to act as suppressors of RF production. Paired blood and synovial fluid samples from 9 patients with RA indicated a significant increase in SF CD8+ cells and DR+ T cells over the corresponding peripheral blood levels. The data suggest that CD8+ cells in RA may respond to immunological abnormalities occurring during the course of the disease.", "contents": "The immunoregulation of rheumatoid factor by the CD8 T lymphocyte subset in rheumatoid arthritis. Flow cytometric analysis on 81 peripheral blood samples from patients with rheumatoid arthritis (RA) showed that levels of serum IgM rheumatoid factor (RF) were associated with the CD8+ cell level. A significant elevation of natural killer (CD56) cell levels was also observed in RA peripheral blood. Using in vitro antibody production techniques, CD8+ cells from patients with RA appeared to act as suppressors of RF production. Paired blood and synovial fluid samples from 9 patients with RA indicated a significant increase in SF CD8+ cells and DR+ T cells over the corresponding peripheral blood levels. The data suggest that CD8+ cells in RA may respond to immunological abnormalities occurring during the course of the disease."} {"id": "PMID:1279168", "title": "Chimeric CD7 monoclonal antibody therapy in rheumatoid arthritis.", "content": "Murine monoclonal antibody (Mab) therapy in patients with rheumatoid arthritis (RA) produces an antimouse immunoglobulin response by the recipient. We studied a chimeric (human/mouse) CD7 Mab, in a dose ranging tolerability study in 10 patients with RA. Modest improvements in disease activity occurred with frequent acute adverse effects of malaise, fever and nausea. After treatment, peripheral blood T lymphocyte numbers fell by 50% and CD7 expression fell by 97% for less than 7 days. Our study demonstrates chimeric Mab function in vivo and illustrates the influence of antibody isotype and patient characteristics on adverse effects.", "contents": "Chimeric CD7 monoclonal antibody therapy in rheumatoid arthritis. Murine monoclonal antibody (Mab) therapy in patients with rheumatoid arthritis (RA) produces an antimouse immunoglobulin response by the recipient. We studied a chimeric (human/mouse) CD7 Mab, in a dose ranging tolerability study in 10 patients with RA. Modest improvements in disease activity occurred with frequent acute adverse effects of malaise, fever and nausea. After treatment, peripheral blood T lymphocyte numbers fell by 50% and CD7 expression fell by 97% for less than 7 days. Our study demonstrates chimeric Mab function in vivo and illustrates the influence of antibody isotype and patient characteristics on adverse effects."} {"id": "PMID:1279169", "title": "Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud's phenomenon.", "content": "Iloprost is a chemically stable analog of prostaglandin I2 showing the same properties as the naturally occurring substance, but with advantages of ease of handling and administration to patients. A double blind within patient comparison of intravenous iloprost and placebo was undertaken in 13 patients with Raynaud's phenomenon severe enough to warrant short term hospitalization for intravenous dilator therapy; thermography was used as one form of assessment. Our results, while showing improvements in frequency of Raynaud's attacks after iloprost compared with placebo, show no significant effects on other variables.", "contents": "Placebo controlled study showing therapeutic benefit of iloprost in the treatment of Raynaud's phenomenon. Iloprost is a chemically stable analog of prostaglandin I2 showing the same properties as the naturally occurring substance, but with advantages of ease of handling and administration to patients. A double blind within patient comparison of intravenous iloprost and placebo was undertaken in 13 patients with Raynaud's phenomenon severe enough to warrant short term hospitalization for intravenous dilator therapy; thermography was used as one form of assessment. Our results, while showing improvements in frequency of Raynaud's attacks after iloprost compared with placebo, show no significant effects on other variables."} {"id": "PMID:1279170", "title": "Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis.", "content": "We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis. Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks. Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion. Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear.", "contents": "Intravenous iloprost treatment of Raynaud's phenomenon and ischemic ulcers secondary to systemic sclerosis. We conducted this study to assess the clinical usefulness and physiologic effects of intravenous iloprost in patients with Raynaud's phenomenon secondary to systemic sclerosis. Thirty-five patients with Raynaud's phenomenon secondary to systemic sclerosis, including 11 with digital ischemic ulcerations, were enrolled in a double blind placebo controlled parallel study in 2 centers. Following a 2 week washout, subjects received intravenous iloprost (0.5-2.0 ng/kg/min) or saline by continuous infusion for 6 h on 5 consecutive days. Clinical assessments, status of digital ulcers, measures of in vivo platelet activation and detailed studies of peripheral vascular response to cold challenge, were performed at entry, at 5 days of therapy and at biweekly intervals for 10 weeks. Complete healing of all cutaneous lesions (ulcers, fissures, and paronychia) was observed 10 weeks after treatment in 6 of 7 patients receiving iloprost versus none of 4 receiving placebo (p = 0.015). Ischemic digital tip ulcers completely healed in all 4 patients with ulcers in the iloprost group, but none in the placebo group (p = 0.029). Patient diaries of frequency, duration and symptoms of Raynaud's phenomenon showed improvement in both groups. Critical ischemic temperature (finger temperature during controlled cold challenge at which Raynaud's or loss of detectable digital blood flow occurred) progressively decreased in the iloprost group from 21.3 +/- 7.3 degrees C at baseline to a minimum of 16.1 +/- 3.2 degrees C at 8 weeks after treatment (p = 0.076), whereas no consistent changes were observed in the placebo group. Treatment was associated with improvement in the rate of skin temperature recovery following cold challenge. No changes were noted in ambient digital skin temperature, total digital blood flow, finger systolic pressure or in measures of in vivo platelet activation. One subject dropped out with chest pain, but adverse effects of nausea, vomiting, headache and jaw pain were otherwise limited to the 5 days of drug infusion. Iloprost appears useful for the treatment of digital ulcers in systemic sclerosis and is associated with evidence of prolonged physiologic improvement although the mechanism of this effect remains unclear."} {"id": "PMID:1279171", "title": "Tenascin and fibronectin distribution in human normal and pathological synovium.", "content": "Tenascin is a glycoprotein found mainly in the extracellular matrix of developing and malignant tissues. The distribution of this molecule in normal and pathological synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) was investigated by indirect immunofluorescence utilizing specific monoclonal antibodies. The same technique was used to study total fibronectin (tFn) in synovial tissues as well as ED-A and ED-B containing fibronectin (Fn) isoforms (A-Fn, B-Fn), generated by alternative splicing of pre-mRNA. Tenascin was found in normal synovium just beneath the whole lining cell layer. However, a higher density and spreading pattern of distribution was observed in OA and RA sections. A-Fn and B-Fn isoforms were prominent and widespread throughout the normal synovial lining; in hypercellular synovial lining (in RA and OA samples), A-Fn and B-Fn were also observed spreading in the sublining, as well as tFn.", "contents": "Tenascin and fibronectin distribution in human normal and pathological synovium. Tenascin is a glycoprotein found mainly in the extracellular matrix of developing and malignant tissues. The distribution of this molecule in normal and pathological synovia from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) was investigated by indirect immunofluorescence utilizing specific monoclonal antibodies. The same technique was used to study total fibronectin (tFn) in synovial tissues as well as ED-A and ED-B containing fibronectin (Fn) isoforms (A-Fn, B-Fn), generated by alternative splicing of pre-mRNA. Tenascin was found in normal synovium just beneath the whole lining cell layer. However, a higher density and spreading pattern of distribution was observed in OA and RA sections. A-Fn and B-Fn isoforms were prominent and widespread throughout the normal synovial lining; in hypercellular synovial lining (in RA and OA samples), A-Fn and B-Fn were also observed spreading in the sublining, as well as tFn."} {"id": "PMID:1279172", "title": "Synthesis and evaluation of 2-pyridinone derivatives as HIV-1 specific reverse transcriptase inhibitors. 1. Phthalimidoalkyl and -alkylamino analogues.", "content": "A potent (IC50 = 30 nM), specific nonnucleoside HIV-1 reverse transcriptase (RT) inhibitor 3-[N-(phthalimidomethyl)amino]-5-ethyl-6-methylpyridin-2(1H) -one (1), was discovered through an in vitro screening program. This compound did not inhibit (IC50 > 300 microns) other DNA and RNA polymerases, including HIV-2 RT and SIV-RT. Unfortunately, hydrolytic instability of this (aminomethyl)phthalimide precluded use as an antiviral agent. In the first paper of this series, preliminary development efforts are described which produced ethylphthalimide 20, a hydrolytically stable compound with reduced (100-fold) HIV-1 RT inhibitory activity and weak (CIC95 = 40 microM) antiviral activity in H9 cells. Structure-activity studies demonstrated the importance of the 5-ethyl, 6-methyl substituent pattern on the pyridinone ring and the need for a flexible two-atom linker between the pyridinone and phthalimide heterocycles. These leads, 1 and 20, provided a basis for the further development of this structural class of inhibitors from which several compounds, the subject of accompanying reports, were selected for clinical evaluation.", "contents": "Synthesis and evaluation of 2-pyridinone derivatives as HIV-1 specific reverse transcriptase inhibitors. 1. Phthalimidoalkyl and -alkylamino analogues. A potent (IC50 = 30 nM), specific nonnucleoside HIV-1 reverse transcriptase (RT) inhibitor 3-[N-(phthalimidomethyl)amino]-5-ethyl-6-methylpyridin-2(1H) -one (1), was discovered through an in vitro screening program. This compound did not inhibit (IC50 > 300 microns) other DNA and RNA polymerases, including HIV-2 RT and SIV-RT. Unfortunately, hydrolytic instability of this (aminomethyl)phthalimide precluded use as an antiviral agent. In the first paper of this series, preliminary development efforts are described which produced ethylphthalimide 20, a hydrolytically stable compound with reduced (100-fold) HIV-1 RT inhibitory activity and weak (CIC95 = 40 microM) antiviral activity in H9 cells. Structure-activity studies demonstrated the importance of the 5-ethyl, 6-methyl substituent pattern on the pyridinone ring and the need for a flexible two-atom linker between the pyridinone and phthalimide heterocycles. These leads, 1 and 20, provided a basis for the further development of this structural class of inhibitors from which several compounds, the subject of accompanying reports, were selected for clinical evaluation."} {"id": "PMID:1279173", "title": "Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 2. Analogues of 3-aminopyridin-2(1H)-one.", "content": "A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC.dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methy lpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents.", "contents": "Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 2. Analogues of 3-aminopyridin-2(1H)-one. A series of nonnucleoside 3-aminopyridin-2(1H)-one derivatives was synthesized and evaluated for HIV-1 RT inhibitory properties. Several analogs proved to be potent and highly selective antagonists with in vitro IC50 values as low as 19 nM in the enzyme assay using rC.dG as template-primer. Two compounds from this series, 3-[[(4,7-dimethylbenzoxazol-2-yl)methyl]-amino]-5-ethyl-6-methy lpyridin-2(1H)-one (34, L-697,639) and the corresponding 4,7-dichloro analogue (37, L-697,661) inhibited the spread of HIV-1 IIIb infection by 95% in MT4 cell culture at concentrations of 25-50 nM and were selected for clinical trials as antiviral agents."} {"id": "PMID:1279174", "title": "Potent gonadotropin releasing hormone antagonists with low histamine-releasing activity.", "content": "The incorporation of Arg residues into position 6 of gonadotropin releasing hormone antagonists had resulted in compounds with increased in vivo potency but also made these analogues potent mast cell degranulators. We have focused on the substitution of position 8 by hArg(R)2 (NG,NG'-dialkylhomoarginine) substitutions, based on the hypotheses that the Arg-Pro sequence is of major importance for this side effect and that shielding of the charge may be an effective way to block degranulation. Analogues in four series were evaluated: (A) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal-(3)3,6,Arg5,hArg(R)2(8),D-+ ++Ala10]GnRH, (B) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)2(5,8),D-Ala10 ]-GnRH, (C) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)2(8),D-Ala10]G nRH, (D) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(R)2(6),hArg(R)2( 8),D-Ala10]GnRH. Although substitution by hArg(Et)2, hArg(Bu), hArg(CH2)3, and hArg(CH2CF3)2 was tested, in each series the hArg(Et)2 residue was superior. Two compounds were considered for clinical evaluation: [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(Et)2(8),D-Ala10] GnRH and [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(Et)2(6),hArg(Et) 2(8),D- Ala10]GnRH (ganirelix acetate). These compounds had high potency for ovulation suppression and low histamine-releasing potency in vitro (ED50 = 0.6, 0.29 microgram/rat and EC50 = 196, 13 micrograms/mL, respectively). Ganirelix is currently in Phase II clinical trials and appears to be the most potent GnRH antagonist tested in humans (based upon ED50 for 24-h suppression of testosterone levels).", "contents": "Potent gonadotropin releasing hormone antagonists with low histamine-releasing activity. The incorporation of Arg residues into position 6 of gonadotropin releasing hormone antagonists had resulted in compounds with increased in vivo potency but also made these analogues potent mast cell degranulators. We have focused on the substitution of position 8 by hArg(R)2 (NG,NG'-dialkylhomoarginine) substitutions, based on the hypotheses that the Arg-Pro sequence is of major importance for this side effect and that shielding of the charge may be an effective way to block degranulation. Analogues in four series were evaluated: (A) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal-(3)3,6,Arg5,hArg(R)2(8),D-+ ++Ala10]GnRH, (B) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)2(5,8),D-Ala10 ]-GnRH, (C) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(R)2(8),D-Ala10]G nRH, (D) [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(R)2(6),hArg(R)2( 8),D-Ala10]GnRH. Although substitution by hArg(Et)2, hArg(Bu), hArg(CH2)3, and hArg(CH2CF3)2 was tested, in each series the hArg(Et)2 residue was superior. Two compounds were considered for clinical evaluation: [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,6,hArg(Et)2(8),D-Ala10] GnRH and [N-Ac-D-Nal(2)1,D-pCl-Phe2,D-Pal(3)3,D-hArg(Et)2(6),hArg(Et) 2(8),D- Ala10]GnRH (ganirelix acetate). These compounds had high potency for ovulation suppression and low histamine-releasing potency in vitro (ED50 = 0.6, 0.29 microgram/rat and EC50 = 196, 13 micrograms/mL, respectively). Ganirelix is currently in Phase II clinical trials and appears to be the most potent GnRH antagonist tested in humans (based upon ED50 for 24-h suppression of testosterone levels)."} {"id": "PMID:1279175", "title": "Haemagglutination profiles of Helicobacter species that cause gastritis in man and animals.", "content": "Thirty-five Helicobacter pylori isolates, 21 H. mustelae isolates and four strains of H. felis were compared for their ability to agglutinate red blood cells (RBCs). Isolates were examined in a slide haemagglutination assay with RBCs from 11 animal species, including rodents, carnivores and primates, as well as man. RBCs were agglutinated by 65-90% of H. mustelae isolates and 16-57% of H. pylori isolates. Treatment of H. mustelae with pronase and heat inhibited haemagglutination (HA) whereas heating only of H. pylori inhibited HA. Treatment of all strains of H. mustelae with trypsin inhibited agglutination of human RBCs; 75% of the treated strains did not agglutinate ferret RBCs. These results suggested that protein(s) may be important haemagglutinins for these bacteria. Variable HA profiles together with varying results after treatment of RBCs with fetuin, D-mannose, and neuraminidase suggested that multiple receptors may be involved in HA reactions with H. pylori and H. mustelae. The observation that H. mustelae and H. pylori agglutinated RBCs of several species and closely adhered to gastric epithelium supported the hypothesis that adherence plays a role in the colonisation and pathogenicity of H. mustelae and H. pylori. H. felis did not adhere to gastric epithelium and did not agglutinate RBCs of any species; nevertheless, H. felis can readily colonise and produce gastritis in several mammals.", "contents": "Haemagglutination profiles of Helicobacter species that cause gastritis in man and animals. Thirty-five Helicobacter pylori isolates, 21 H. mustelae isolates and four strains of H. felis were compared for their ability to agglutinate red blood cells (RBCs). Isolates were examined in a slide haemagglutination assay with RBCs from 11 animal species, including rodents, carnivores and primates, as well as man. RBCs were agglutinated by 65-90% of H. mustelae isolates and 16-57% of H. pylori isolates. Treatment of H. mustelae with pronase and heat inhibited haemagglutination (HA) whereas heating only of H. pylori inhibited HA. Treatment of all strains of H. mustelae with trypsin inhibited agglutination of human RBCs; 75% of the treated strains did not agglutinate ferret RBCs. These results suggested that protein(s) may be important haemagglutinins for these bacteria. Variable HA profiles together with varying results after treatment of RBCs with fetuin, D-mannose, and neuraminidase suggested that multiple receptors may be involved in HA reactions with H. pylori and H. mustelae. The observation that H. mustelae and H. pylori agglutinated RBCs of several species and closely adhered to gastric epithelium supported the hypothesis that adherence plays a role in the colonisation and pathogenicity of H. mustelae and H. pylori. H. felis did not adhere to gastric epithelium and did not agglutinate RBCs of any species; nevertheless, H. felis can readily colonise and produce gastritis in several mammals."} {"id": "PMID:1279176", "title": "Inhibition of rat alveolar macrophage phagocytic function by a Pseudomonas cepacia lipase.", "content": "The effects of purified Pseudomonas cepacia lipase on rat pulmonary alveolar function and morphology were examined. Lipase (2.5-20 micrograms/ml) adversely effected the phagocytic function of rat pulmonary alveolar macrophages in a dose-dependent manner. The lipase itself was not directly cytotoxic to these cells. Alveolar macrophages, in the absence of lipase, phagocytosed c. 35% of a given population of opsonised P. cepacia in 30 min when the ratio of bacteria:phagocyte was 10:1. Phagocytosis of P. cepacia by rat pulmonary alveolar macrophages was significantly reduced when the cells were either pre-incubated with the lipase or when phagocytosis occurred in the presence of the lipase. This was confirmed by transmission electronmicroscopy. These functional changes were associated with marked alterations of the macrophage morphology. Scanning electronmicroscopy showed that macrophages exposed to the P. cepacia lipase had fewer specialised surface structures and did not spread on plastic surfaces as well as untreated macrophages. The effects of the lipase were lost after heat inactivation, which indicates that the effects of the P. cepacia lipase were due to its enzymic activity. These results suggest that, if sufficient quantities of the enzyme are produced in vivo, lipase may be an important virulence factor for P. cepacia, allowing the organism to evade phagocytic cells.", "contents": "Inhibition of rat alveolar macrophage phagocytic function by a Pseudomonas cepacia lipase. The effects of purified Pseudomonas cepacia lipase on rat pulmonary alveolar function and morphology were examined. Lipase (2.5-20 micrograms/ml) adversely effected the phagocytic function of rat pulmonary alveolar macrophages in a dose-dependent manner. The lipase itself was not directly cytotoxic to these cells. Alveolar macrophages, in the absence of lipase, phagocytosed c. 35% of a given population of opsonised P. cepacia in 30 min when the ratio of bacteria:phagocyte was 10:1. Phagocytosis of P. cepacia by rat pulmonary alveolar macrophages was significantly reduced when the cells were either pre-incubated with the lipase or when phagocytosis occurred in the presence of the lipase. This was confirmed by transmission electronmicroscopy. These functional changes were associated with marked alterations of the macrophage morphology. Scanning electronmicroscopy showed that macrophages exposed to the P. cepacia lipase had fewer specialised surface structures and did not spread on plastic surfaces as well as untreated macrophages. The effects of the lipase were lost after heat inactivation, which indicates that the effects of the P. cepacia lipase were due to its enzymic activity. These results suggest that, if sufficient quantities of the enzyme are produced in vivo, lipase may be an important virulence factor for P. cepacia, allowing the organism to evade phagocytic cells."} {"id": "PMID:1279178", "title": "Reconstitution of channels from preparations enriched in lens gap junction protein MP70.", "content": "Detergent-solubilized ovine lens membrane proteins, enriched in the 70-kDa gap junction component (MP70), were reconstituted into planar lipid bilayers and analyzed for channel activities. Three distinct activities were found. Those showing conductance steps of 290 pS (symmetrical 150-mM KCl solutions) had properties similar to those reported earlier for MIP26 (Ehring, G.R., Zampighi, G., Horwitz, J., Bok, D., Hall, J.E. 1990. J. Gen. Physiol. 96:631-664.) of which minor amounts were normally present in the detergent-solubilized preparations. Two novel channel activities had unitary conductances of 90 and 45 pS, were halothane sensitive and did not discriminate between sodium and potassium ions. The 90-pS channel was asymmetrically voltage dependent, and its properties would be consistent with the expected properties of junctional hemichannels.", "contents": "Reconstitution of channels from preparations enriched in lens gap junction protein MP70. Detergent-solubilized ovine lens membrane proteins, enriched in the 70-kDa gap junction component (MP70), were reconstituted into planar lipid bilayers and analyzed for channel activities. Three distinct activities were found. Those showing conductance steps of 290 pS (symmetrical 150-mM KCl solutions) had properties similar to those reported earlier for MIP26 (Ehring, G.R., Zampighi, G., Horwitz, J., Bok, D., Hall, J.E. 1990. J. Gen. Physiol. 96:631-664.) of which minor amounts were normally present in the detergent-solubilized preparations. Two novel channel activities had unitary conductances of 90 and 45 pS, were halothane sensitive and did not discriminate between sodium and potassium ions. The 90-pS channel was asymmetrically voltage dependent, and its properties would be consistent with the expected properties of junctional hemichannels."} {"id": "PMID:1279177", "title": "Model ion channels: gramicidin and alamethicin.", "content": "We have discussed in some detail a variety of experimental studies which were designed to elucidate the conformational and dynamic properties of gramicidin and alamethicin. Although the behavior of these peptides is by no means fully characterized, these studies have already permitted aspects of ion channel activity to be understood in molecular terms. Studies with gramicidin in a variety of organic solutions have revealed conformational heterogeneity of this peptide; at least five major isomers exist, several of which have been characterized in detail using NMR spectroscopy and X-ray crystallography. When added to lipid membranes gramicidin undergoes a further conformational conversion. Although the conformation of gramicidin in membranes is not as well characterized as the solution conformation(s) and an X-ray structure is not yet available, detailed data, particularly from solid-state NMR studies, continue to become available and a right-handed beta 6.3 helical conformation of the peptide backbone is now generally accepted. Two of these beta 6.3 helices joined at their N-termini are believed to form the conducting channel. The conformational behavior of the side-chains of gramicidin in the membrane-bound form is not well established and several NMR, CD, fluorescence and theoretical studies are now focussed on this. Although the side-chains do not directly contact the permeating ions, they can have distinct effects on conductance and selectivity by altering the electrostatic environment sensed by the ion. The dynamics of both side-chain and backbone conformations of gramicidin appear critical to a detailed understanding of the ion transport process in this channel. As the description of the membrane-bound conformation of gramicidin becomes more detailed, simulations of ion transport using computational methods are likely to improve and will further our understanding of the processes of ion transport. As well as internal motion of the backbone and side-chains, gramicidin undergoes rotational and translational motion in the plane of the membrane. These motions do not appear to be essential for the process of ion transport but can affect channel lifetime since lifetime is determined by the rate of association and dissociation of gramicidin monomers. Gramicidin-membrane interactions are also likely to be involved in the frequency of occurrence of channel subconductance states, the frequency of channel flickering and fundamentally in the stability of the membrane-bound gramicidin conformation. Alamethicin forms channels in membranes which are strongly voltage-dependent. The molecular origin of voltage-dependent conductances has been a fundamental problem in biophysics for many years.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Model ion channels: gramicidin and alamethicin. We have discussed in some detail a variety of experimental studies which were designed to elucidate the conformational and dynamic properties of gramicidin and alamethicin. Although the behavior of these peptides is by no means fully characterized, these studies have already permitted aspects of ion channel activity to be understood in molecular terms. Studies with gramicidin in a variety of organic solutions have revealed conformational heterogeneity of this peptide; at least five major isomers exist, several of which have been characterized in detail using NMR spectroscopy and X-ray crystallography. When added to lipid membranes gramicidin undergoes a further conformational conversion. Although the conformation of gramicidin in membranes is not as well characterized as the solution conformation(s) and an X-ray structure is not yet available, detailed data, particularly from solid-state NMR studies, continue to become available and a right-handed beta 6.3 helical conformation of the peptide backbone is now generally accepted. Two of these beta 6.3 helices joined at their N-termini are believed to form the conducting channel. The conformational behavior of the side-chains of gramicidin in the membrane-bound form is not well established and several NMR, CD, fluorescence and theoretical studies are now focussed on this. Although the side-chains do not directly contact the permeating ions, they can have distinct effects on conductance and selectivity by altering the electrostatic environment sensed by the ion. The dynamics of both side-chain and backbone conformations of gramicidin appear critical to a detailed understanding of the ion transport process in this channel. As the description of the membrane-bound conformation of gramicidin becomes more detailed, simulations of ion transport using computational methods are likely to improve and will further our understanding of the processes of ion transport. As well as internal motion of the backbone and side-chains, gramicidin undergoes rotational and translational motion in the plane of the membrane. These motions do not appear to be essential for the process of ion transport but can affect channel lifetime since lifetime is determined by the rate of association and dissociation of gramicidin monomers. Gramicidin-membrane interactions are also likely to be involved in the frequency of occurrence of channel subconductance states, the frequency of channel flickering and fundamentally in the stability of the membrane-bound gramicidin conformation. Alamethicin forms channels in membranes which are strongly voltage-dependent. The molecular origin of voltage-dependent conductances has been a fundamental problem in biophysics for many years.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279179", "title": "Several regions of a tRNA precursor determine the Escherichia coli RNase P cleavage site.", "content": "The RNase P cleavage reaction was studied as a function of the number of base-pairs in the acceptor-stem and/or T-stem of a natural tRNA precursor, the tRNA(Tyr)Su3 precursor. Our data suggest that the location of the Escherichia coli RNase P cleavage site does not depend merely on the lengths of the acceptor-stem and T-stem as previously suggested. Surprisingly, we find that precursors with only four base-pairs in the acceptor-stem are cleaved by M1 RNA and by holoenzyme. Furthermore, we show that both disruption of base-pairing, and alteration of the nucleotide sequence (without disruption of base-pairing) proximal to the cleavage site result in aberrant cleavage. Thus, the identity of the nucleotides near the cleavage site is important for recognition of the cleavage site rather than base-pairing. The important nucleotides are those at positions -2, -1, +1, +72, +73 and +74. We propose that the nucleotide at position +1 functions as a guiding nucleotide. These results raise the possibility that Mg2+ binding near the cleavage site is dependent on the identity of the nucleotides at these positions. In addition, we show that disruption of base-pairing in the acceptor-stem affects both Michaelis-Menten constants, Km and kcat.", "contents": "Several regions of a tRNA precursor determine the Escherichia coli RNase P cleavage site. The RNase P cleavage reaction was studied as a function of the number of base-pairs in the acceptor-stem and/or T-stem of a natural tRNA precursor, the tRNA(Tyr)Su3 precursor. Our data suggest that the location of the Escherichia coli RNase P cleavage site does not depend merely on the lengths of the acceptor-stem and T-stem as previously suggested. Surprisingly, we find that precursors with only four base-pairs in the acceptor-stem are cleaved by M1 RNA and by holoenzyme. Furthermore, we show that both disruption of base-pairing, and alteration of the nucleotide sequence (without disruption of base-pairing) proximal to the cleavage site result in aberrant cleavage. Thus, the identity of the nucleotides near the cleavage site is important for recognition of the cleavage site rather than base-pairing. The important nucleotides are those at positions -2, -1, +1, +72, +73 and +74. We propose that the nucleotide at position +1 functions as a guiding nucleotide. These results raise the possibility that Mg2+ binding near the cleavage site is dependent on the identity of the nucleotides at these positions. In addition, we show that disruption of base-pairing in the acceptor-stem affects both Michaelis-Menten constants, Km and kcat."} {"id": "PMID:1279180", "title": "Fluorine-19 nuclear magnetic resonance as a probe of the solution structure of mutants of 5-fluorouracil-substituted Escherichia coli valine tRNA.", "content": "In order to utilize 19F nuclear magnetic resonance (NMR) to probe the solution structure of Escherichia coli tRNAVal labeled by incorporation of 5-fluorouracil, we have assigned its 19F spectrum. We describe here assignments made by examining the spectra of a series of tRNAVal mutants with nucleotide substitutions for individual 5-fluorouracil residues. The result of base replacements on the structure and function of the tRNA are also characterized. Mutants were prepared by oligonucleotide-directed mutagenesis of a cloned tRNAVal gene, and the tRNAs transcribed in vitro by bacteriophage T7 RNA polymerase. By identifying the missing peak in the 19F NMR spectrum of each tRNA variant we were able to assign resonances from fluorouracil residues in loop and stem regions of the tRNA. As a result of the assignment of FU33, FU34 and FU29, temperature-dependent spectral shifts could be attributed to changes in anticodon loop and stem conformation. Observation of a magnesium ion-dependent splitting of the resonance assigned to FU64 suggested that the T-arm of tRNAVal can exist in two conformations in slow exchange on the NMR time scale. Replacement of most 5-fluorouracil residues in loops and stems had little effect on the structure of tRNAVal; few shifts in the 19F NMR spectrum of the mutant tRNAs were noted. However, replacing the FU29.A41 base-pair in the anticodon stem with C29.G41 induced conformational changes in the anticodon loop as well as in the P-10 loop. Effects of nucleotide substitution on aminoacylation were determined by comparing the Vmax and Km values of tRNAVal mutants with those of the wild-type tRNA. Nucleotide substitution at the 3' end of the anticodon (position 36) reduced the aminoacylation efficiency (Vmax/Km) of tRNAVal by three orders of magnitude. Base replacement at the 5' end of the anticodon (position 34) had only a small negative effect on the aminoacylation efficiency. Substitution of the FU29.A41 base-pair increased the Km value 20-fold, while Vmax remained almost unchanged. The FU4.A69 base-pair in the acceptor stem, could readily be replaced with little effect on the aminoacylation efficiency of E. coli tRNAVal, indicating that this base-pair is not an identity element of the tRNA, as suggested by others.", "contents": "Fluorine-19 nuclear magnetic resonance as a probe of the solution structure of mutants of 5-fluorouracil-substituted Escherichia coli valine tRNA. In order to utilize 19F nuclear magnetic resonance (NMR) to probe the solution structure of Escherichia coli tRNAVal labeled by incorporation of 5-fluorouracil, we have assigned its 19F spectrum. We describe here assignments made by examining the spectra of a series of tRNAVal mutants with nucleotide substitutions for individual 5-fluorouracil residues. The result of base replacements on the structure and function of the tRNA are also characterized. Mutants were prepared by oligonucleotide-directed mutagenesis of a cloned tRNAVal gene, and the tRNAs transcribed in vitro by bacteriophage T7 RNA polymerase. By identifying the missing peak in the 19F NMR spectrum of each tRNA variant we were able to assign resonances from fluorouracil residues in loop and stem regions of the tRNA. As a result of the assignment of FU33, FU34 and FU29, temperature-dependent spectral shifts could be attributed to changes in anticodon loop and stem conformation. Observation of a magnesium ion-dependent splitting of the resonance assigned to FU64 suggested that the T-arm of tRNAVal can exist in two conformations in slow exchange on the NMR time scale. Replacement of most 5-fluorouracil residues in loops and stems had little effect on the structure of tRNAVal; few shifts in the 19F NMR spectrum of the mutant tRNAs were noted. However, replacing the FU29.A41 base-pair in the anticodon stem with C29.G41 induced conformational changes in the anticodon loop as well as in the P-10 loop. Effects of nucleotide substitution on aminoacylation were determined by comparing the Vmax and Km values of tRNAVal mutants with those of the wild-type tRNA. Nucleotide substitution at the 3' end of the anticodon (position 36) reduced the aminoacylation efficiency (Vmax/Km) of tRNAVal by three orders of magnitude. Base replacement at the 5' end of the anticodon (position 34) had only a small negative effect on the aminoacylation efficiency. Substitution of the FU29.A41 base-pair increased the Km value 20-fold, while Vmax remained almost unchanged. The FU4.A69 base-pair in the acceptor stem, could readily be replaced with little effect on the aminoacylation efficiency of E. coli tRNAVal, indicating that this base-pair is not an identity element of the tRNA, as suggested by others."} {"id": "PMID:1279181", "title": "Correlations between fluorine-19 nuclear magnetic resonance chemical shift and the secondary and tertiary structure of 5-fluorouracil-substituted tRNA.", "content": "To complete assignment of the 19F nuclear magnetic resonance (NMR) spectrum of 5-fluorouracil-substituted Escherichia coli tRNA(Val), resonances from 5-fluorouracil residues involved in tertiary interactions have been identified. Because these assignments could not be made directly by the base-replacement method used to assign 5-fluorouracil residues in loop and stem regions of the tRNA, alternative assignment strategies were employed. FU54 and FU55 were identified by 19F homonuclear Overhauser experiments and were then assigned by comparison of their 19F NMR spectra with those of 5-fluorouracil-labeled yeast tRNA(Phe) mutants having FU54 replaced by adenine and FU55 replaced by cytosine. FU8 and FU12, were assigned from the 19F NMR spectrum of the tRNA(Val) mutant in which the base triple G9-C23-G12 substituted for the wild-type A9-A23-FU12. Although replacement of the conserved U8 (FU8) with A or C disrupts the tertiary structure of tRNA(Val), it has only a small effect on the catalytic turnover number of valyl-tRNA synthetase, while reducing the affinity of the tRNA for enzyme. Analysis of the 19F chemical shift assignments of all 14 resonances in the spectrum of 5-fluorouracil-substituted tRNAVal indicated a strong correlation to tRNA secondary and tertiary structure. 5-Fluorouracil residues in loop regions gave rise to peaks in the central region of the spectrum, 4.4 to 4.9 parts per million (p.p.m.) downfield from free 5-fluorouracil. However, the signal from FU59, in the T-loop of tRNA(Val), was shifted more than 1 p.p.m. downfield, to 5.9 p.p.m., presumably because of the involvement of this fluorouracil in the tertiary interactions between the T and D-loops. The 19F chemical shift moved upfield, to the 2.0 to 2.8 p.p.m. range, when fluorouracil was base-paired with adenine in helical stems. This upfield shift was less pronounced for the fluorine of the FU7.A66 base-pair, located at the base of the acceptor stem, an indication that FU7 is only partially stacked on the adjacent G49 in the continuous acceptor stem/T-stem helix. An unanticipated finding was that the 19F resonances of 5-fluorouracil residues wobble base-paired with guanine were shifted 4 to 5 p.p.m. downfield of those from fluorouracil residues paired with A. In the 19F NMR spectra of all fluorinated tRNAs studied, the farthest downfield peak corresponded to FU55, which replaced the conserved pseudouridine normally found at this position.", "contents": "Correlations between fluorine-19 nuclear magnetic resonance chemical shift and the secondary and tertiary structure of 5-fluorouracil-substituted tRNA. To complete assignment of the 19F nuclear magnetic resonance (NMR) spectrum of 5-fluorouracil-substituted Escherichia coli tRNA(Val), resonances from 5-fluorouracil residues involved in tertiary interactions have been identified. Because these assignments could not be made directly by the base-replacement method used to assign 5-fluorouracil residues in loop and stem regions of the tRNA, alternative assignment strategies were employed. FU54 and FU55 were identified by 19F homonuclear Overhauser experiments and were then assigned by comparison of their 19F NMR spectra with those of 5-fluorouracil-labeled yeast tRNA(Phe) mutants having FU54 replaced by adenine and FU55 replaced by cytosine. FU8 and FU12, were assigned from the 19F NMR spectrum of the tRNA(Val) mutant in which the base triple G9-C23-G12 substituted for the wild-type A9-A23-FU12. Although replacement of the conserved U8 (FU8) with A or C disrupts the tertiary structure of tRNA(Val), it has only a small effect on the catalytic turnover number of valyl-tRNA synthetase, while reducing the affinity of the tRNA for enzyme. Analysis of the 19F chemical shift assignments of all 14 resonances in the spectrum of 5-fluorouracil-substituted tRNAVal indicated a strong correlation to tRNA secondary and tertiary structure. 5-Fluorouracil residues in loop regions gave rise to peaks in the central region of the spectrum, 4.4 to 4.9 parts per million (p.p.m.) downfield from free 5-fluorouracil. However, the signal from FU59, in the T-loop of tRNA(Val), was shifted more than 1 p.p.m. downfield, to 5.9 p.p.m., presumably because of the involvement of this fluorouracil in the tertiary interactions between the T and D-loops. The 19F chemical shift moved upfield, to the 2.0 to 2.8 p.p.m. range, when fluorouracil was base-paired with adenine in helical stems. This upfield shift was less pronounced for the fluorine of the FU7.A66 base-pair, located at the base of the acceptor stem, an indication that FU7 is only partially stacked on the adjacent G49 in the continuous acceptor stem/T-stem helix. An unanticipated finding was that the 19F resonances of 5-fluorouracil residues wobble base-paired with guanine were shifted 4 to 5 p.p.m. downfield of those from fluorouracil residues paired with A. In the 19F NMR spectra of all fluorinated tRNAs studied, the farthest downfield peak corresponded to FU55, which replaced the conserved pseudouridine normally found at this position."} {"id": "PMID:1279182", "title": "Crystallization and preliminary X-ray crystallographic analysis of lipase from Pseudomonas cepacia.", "content": "Large crystals of lipase from Pseudomonas cepacia have been grown at room temperature from solutions containing 2-methyl-2,4-pentanediol and sodium citrate. They grow within two weeks to typical dimensions of 1.0 mm x 0.5 mm x 0.3 mm. The crystals belong to the monoclinic space group P2(1), with unit cell parameters a = 84.91 A, b = 47.33 A, c = 86.00 A, and beta = 116.09 degrees. And they diffract to about 1.6 A upon exposure to synchroton X-rays. X-ray data have been collected to 2.2 A Bragg spacing from a native crystal.", "contents": "Crystallization and preliminary X-ray crystallographic analysis of lipase from Pseudomonas cepacia. Large crystals of lipase from Pseudomonas cepacia have been grown at room temperature from solutions containing 2-methyl-2,4-pentanediol and sodium citrate. They grow within two weeks to typical dimensions of 1.0 mm x 0.5 mm x 0.3 mm. The crystals belong to the monoclinic space group P2(1), with unit cell parameters a = 84.91 A, b = 47.33 A, c = 86.00 A, and beta = 116.09 degrees. And they diffract to about 1.6 A upon exposure to synchroton X-rays. X-ray data have been collected to 2.2 A Bragg spacing from a native crystal."} {"id": "PMID:1279183", "title": "Role of the SIKVAV site of laminin in promotion of angiogenesis and tumor growth: an in vivo Matrigel model.", "content": "Angiogenesis (vascularization) has a critical role in tumor growth and metastasis, and peptides containing the SIKVAV amino acid sequence (Ser-Ile-Lys-Val-Ala-Val) have been shown to stimulate many angiogenic activities in vitro. The use of model systems to identify agents that stimulate or inhibit angiogenesis may lead to the development of new antitumor strategies. Our purpose was to use an in vivo murine model system to study the angiogenic activity of a synthetic peptide derived from the laminin A protein chain and containing the SIKVAV amino acid sequence. We also examined the ability of the peptide to enhance tumor growth in vivo. The SIKVAV-containing peptide was mixed with Matrigel, a reconstituted basement membrane extract used to assay stimulation of angiogenesis. The mixture was subcutaneously injected into C57BL/6 mice. At various times after injection, the Matrigel plug was excised, and angiogenic activity was assessed by histologic examination and immunohistochemical staining with an antibody to the von Willebrand factor (vWF), an endothelium-specific antigen. In other experiments, the mixture of peptide and Matrigel was co-injected with B16F10 murine melanoma cells into C57BL/6 mice, and the resultant tumors were assessed for size and vascularization. When co-injected with Matrigel at doses as low as 10 micrograms, the SIKVAV-containing peptide stimulated angiogenesis fourfold greater than that seen in controls, and maximum angiogenic activity was observed 2 weeks after injection. This peptide was angiogenic in a dose-dependent manner up to a 100-micrograms dose. When co-injected with Matrigel and B16F10 melanoma cells, the peptide enhanced tumor growth by approximately 2.5-fold, and tumor vascularization was significantly increased (P = .027) over that observed after injection with melanoma cells and Matrigel alone. These data demonstrate that the laminin-derived SIKVAV-containing peptide is angiogenic in a new in vivo model system and can enhance tumor vascularization and growth.", "contents": "Role of the SIKVAV site of laminin in promotion of angiogenesis and tumor growth: an in vivo Matrigel model. Angiogenesis (vascularization) has a critical role in tumor growth and metastasis, and peptides containing the SIKVAV amino acid sequence (Ser-Ile-Lys-Val-Ala-Val) have been shown to stimulate many angiogenic activities in vitro. The use of model systems to identify agents that stimulate or inhibit angiogenesis may lead to the development of new antitumor strategies. Our purpose was to use an in vivo murine model system to study the angiogenic activity of a synthetic peptide derived from the laminin A protein chain and containing the SIKVAV amino acid sequence. We also examined the ability of the peptide to enhance tumor growth in vivo. The SIKVAV-containing peptide was mixed with Matrigel, a reconstituted basement membrane extract used to assay stimulation of angiogenesis. The mixture was subcutaneously injected into C57BL/6 mice. At various times after injection, the Matrigel plug was excised, and angiogenic activity was assessed by histologic examination and immunohistochemical staining with an antibody to the von Willebrand factor (vWF), an endothelium-specific antigen. In other experiments, the mixture of peptide and Matrigel was co-injected with B16F10 murine melanoma cells into C57BL/6 mice, and the resultant tumors were assessed for size and vascularization. When co-injected with Matrigel at doses as low as 10 micrograms, the SIKVAV-containing peptide stimulated angiogenesis fourfold greater than that seen in controls, and maximum angiogenic activity was observed 2 weeks after injection. This peptide was angiogenic in a dose-dependent manner up to a 100-micrograms dose. When co-injected with Matrigel and B16F10 melanoma cells, the peptide enhanced tumor growth by approximately 2.5-fold, and tumor vascularization was significantly increased (P = .027) over that observed after injection with melanoma cells and Matrigel alone. These data demonstrate that the laminin-derived SIKVAV-containing peptide is angiogenic in a new in vivo model system and can enhance tumor vascularization and growth."} {"id": "PMID:1279184", "title": "Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet.", "content": "Mutations of the p53 tumor suppressor gene have been reported in 50% of patients with hepatocellular carcinoma (HCC) from China and South Africa. These reports suggested an association of p53 mutations with high levels of aflatoxin in the diet. Most studies of p53 and HCC, however, have not fully evaluated the possible role of the hepatitis B virus (HBV). Aflatoxin is a substance produced by food mold that is known to cause HCC in experimental animals. The purpose of this study was to evaluate the relationship of p53 gene mutation to high or low levels of aflatoxin in the diet and to HBV infection. p53 protein and hepatitis B surface antigen (HBsAg) were evaluated by immunohistochemistry using the avidin-biotin-peroxidase system in paraffin-embedded specimens of HCC and of adjacent nontumorous liver tissue from 43 patients. Tissue specimens from three normal human livers were also evaluated. HCCs and adjacent nontumorous liver tissues were obtained from 23 patients from Qidong, China, where aflatoxin levels in the diet are high, and from 20 patients from two regions in the United States (patients from the National Institutes of Health, Bethesda, Md., and Kuakini Medical Center, Honolulu, Hawaii), where aflatoxin levels in the diet are low. Mutant p53 protein was detected in the nuclei of HCCs from 14 (61%) of 23 patients from China and from three (30%) of 10 patients and six (60%) of 10 patients, respectively, from the two regions of the United States. A statistically significant association between detection of mutant p53 protein in HCC cells and the detection of HBsAg in hepatocytes of the adjacent nontumorous liver tissue was observed in patients from China and the United States considered together. Mutations of the tumor suppressor gene p53 in hepatocellular carcinomas are not limited to patients from geographic regions where the ingestion of aflatoxin is high. In many patients, these mutations may be associated with HBV infection. The possible interaction of chronic HBV infection and p53 gene mutation, suggested by these data, indicates a mechanism by which HBV infection beginning early in life could contribute to the subsequent development of HCC.", "contents": "Mutations of p53 gene in hepatocellular carcinoma: roles of hepatitis B virus and aflatoxin contamination in the diet. Mutations of the p53 tumor suppressor gene have been reported in 50% of patients with hepatocellular carcinoma (HCC) from China and South Africa. These reports suggested an association of p53 mutations with high levels of aflatoxin in the diet. Most studies of p53 and HCC, however, have not fully evaluated the possible role of the hepatitis B virus (HBV). Aflatoxin is a substance produced by food mold that is known to cause HCC in experimental animals. The purpose of this study was to evaluate the relationship of p53 gene mutation to high or low levels of aflatoxin in the diet and to HBV infection. p53 protein and hepatitis B surface antigen (HBsAg) were evaluated by immunohistochemistry using the avidin-biotin-peroxidase system in paraffin-embedded specimens of HCC and of adjacent nontumorous liver tissue from 43 patients. Tissue specimens from three normal human livers were also evaluated. HCCs and adjacent nontumorous liver tissues were obtained from 23 patients from Qidong, China, where aflatoxin levels in the diet are high, and from 20 patients from two regions in the United States (patients from the National Institutes of Health, Bethesda, Md., and Kuakini Medical Center, Honolulu, Hawaii), where aflatoxin levels in the diet are low. Mutant p53 protein was detected in the nuclei of HCCs from 14 (61%) of 23 patients from China and from three (30%) of 10 patients and six (60%) of 10 patients, respectively, from the two regions of the United States. A statistically significant association between detection of mutant p53 protein in HCC cells and the detection of HBsAg in hepatocytes of the adjacent nontumorous liver tissue was observed in patients from China and the United States considered together. Mutations of the tumor suppressor gene p53 in hepatocellular carcinomas are not limited to patients from geographic regions where the ingestion of aflatoxin is high. In many patients, these mutations may be associated with HBV infection. The possible interaction of chronic HBV infection and p53 gene mutation, suggested by these data, indicates a mechanism by which HBV infection beginning early in life could contribute to the subsequent development of HCC."} {"id": "PMID:1279186", "title": "Inhibition by pentosan polysulfate (PPS) of heparin-binding growth factors released from tumor cells and blockage by PPS of tumor growth in animals.", "content": "In a proliferating tumor, locally secreted polypeptide growth factors, which have autocrine and paracrine functions, induce vascularization essential for tumor growth and metastasis. These growth factors may serve as targets for tumor therapy. We have shown that the heparinoid pentosan polysulfate (PPS) can block growth of subcutaneous human tumor xenografts in nude mice and angiogenesis induced by the heparin-binding, Kaposi's sarcoma-derived fibroblast growth factor (K-FGF). The purpose of this study was to determine whether PPS might also interfere with stimulation of endothelial cells by other growth factors released from tumor cells and whether the promising antitumor effects of PPS extend to other human tumor cell lines. We studied the effects of PPS on stimulation by heparin-binding growth factors released from seven human tumor cell lines in vitro and on tumors growing from these cell lines in athymic nude mice. Seven human cell lines established from breast, prostate, epidermoid, and lung carcinomas and rhabdomyosarcoma were used in in vivo as well as in vitro studies of the effects of PPS. We also studied in vitro the effects of PPS on growth factor-induced colony formation of normal rat kidney fibroblasts and human adrenal carcinoma cells. The tumor cell lines released growth factors into their media that stimulated growth of endothelial and epithelial cells as well as fibroblasts. Heparin-affinity chromatography showed that heparin-binding growth factors contributed substantially to this paracrine activity and that PPS inhibited this stimulus. Six of the seven tumor cell lines were resistant to PPS in soft-agar cloning assays and hence did not appear to depend on autocrine stimulation by the heparin-binding growth factors. In contrast to this in vitro resistance, subcutaneous growth of tumors from all cell lines in athymic nude mice was inhibited in a dose-dependent fashion by daily intraperitoneal injections of PPS. We conclude that heparin-binding growth factors contribute substantially to tumor growth in vivo and that PPS acts by blocking the paracrine effects of heparin-binding growth factors released from the tumor cells. PPS could become a novel treatment tool targeting tumor growth factors.", "contents": "Inhibition by pentosan polysulfate (PPS) of heparin-binding growth factors released from tumor cells and blockage by PPS of tumor growth in animals. In a proliferating tumor, locally secreted polypeptide growth factors, which have autocrine and paracrine functions, induce vascularization essential for tumor growth and metastasis. These growth factors may serve as targets for tumor therapy. We have shown that the heparinoid pentosan polysulfate (PPS) can block growth of subcutaneous human tumor xenografts in nude mice and angiogenesis induced by the heparin-binding, Kaposi's sarcoma-derived fibroblast growth factor (K-FGF). The purpose of this study was to determine whether PPS might also interfere with stimulation of endothelial cells by other growth factors released from tumor cells and whether the promising antitumor effects of PPS extend to other human tumor cell lines. We studied the effects of PPS on stimulation by heparin-binding growth factors released from seven human tumor cell lines in vitro and on tumors growing from these cell lines in athymic nude mice. Seven human cell lines established from breast, prostate, epidermoid, and lung carcinomas and rhabdomyosarcoma were used in in vivo as well as in vitro studies of the effects of PPS. We also studied in vitro the effects of PPS on growth factor-induced colony formation of normal rat kidney fibroblasts and human adrenal carcinoma cells. The tumor cell lines released growth factors into their media that stimulated growth of endothelial and epithelial cells as well as fibroblasts. Heparin-affinity chromatography showed that heparin-binding growth factors contributed substantially to this paracrine activity and that PPS inhibited this stimulus. Six of the seven tumor cell lines were resistant to PPS in soft-agar cloning assays and hence did not appear to depend on autocrine stimulation by the heparin-binding growth factors. In contrast to this in vitro resistance, subcutaneous growth of tumors from all cell lines in athymic nude mice was inhibited in a dose-dependent fashion by daily intraperitoneal injections of PPS. We conclude that heparin-binding growth factors contribute substantially to tumor growth in vivo and that PPS acts by blocking the paracrine effects of heparin-binding growth factors released from the tumor cells. PPS could become a novel treatment tool targeting tumor growth factors."} {"id": "PMID:1279187", "title": "Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275.", "content": "Previous studies have shown that polyhydroxylated flavonoids such as quercetin and genistein can inhibit tumor cell growth in vitro, and preliminary in vivo studies of the flavone L86-8275 have shown growth inhibition of LX529 and A549 lung carcinomas. L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8[4-(3-hydroxy-1-methyl)- piperidinyl]-4H-1-benzopyran-4-one] is a flavone of novel structure. The purpose of this study was to determine in vitro whether L86-8275 is a more potent inhibitor of growth in breast carcinoma and lung carcinoma cells than quercetin or genistein. We studied the effects of L86-8275 on cell growth in seven breast carcinoma cell lines and five lung carcinoma cell lines. MDA468 breast carcinoma was then selected for further study. Cell proliferation was measured by a colorimetric dye reduction assay; synthesis of DNA, RNA, and protein by incorporation of the radioactive metabolic precursors thymidine, uridine, or leucine, respectively; adenosine triphosphate (ATP) content by a luciferase-mediated bioluminescence reaction; and cell cycle progression by the use of cell-synchronizing drugs (aphidicolin and nocodazole) and flow cytometry. L86-8275 was not cytotoxic to stationary-phase cells but reversibly inhibited the growth of cells in exponential growth phase. At concentrations of 25-160 nM, L86-8275 inhibited growth of human breast and lung carcinoma cell lines by 50%. MDA468 breast carcinoma cells were 60-fold and 400-fold more sensitive to L86-8275 than to quercetin and genistein, respectively. By 24 hours after addition of L86-8275, DNA synthesis in MDA468 cells was inhibited by greater than 95%, protein synthesis by 80%, and RNA synthesis by 40%-60%, under conditions that preserved cellular ATP levels at approximately 80%-90% of control values. When MDA468 cells released from aphidicolin-induced cell cycle arrest were exposed to 200 nM L86-8275, they completed the S phase but arrested in G2. When cells released from nocodazole-induced cell cycle arrest were exposed to 200 nM L86-8275, they completed mitosis but arrested in G1. L86-8275 is a potent, yet reversible, growth-inhibitory flavone that can selectively block cell cycle progression in vitro at more than one point in the cell cycle. These findings suggest that L86-8275 is a candidate for further preclinical development, as well as a model for the synthesis of other flavonoids that might potently delay cell cycle progression to achieve inhibition of tumor growth. Future studies need to address optimal schedules for antiproliferative activity in vivo and inhibition of clonogenic activity.", "contents": "Growth inhibition with reversible cell cycle arrest of carcinoma cells by flavone L86-8275. Previous studies have shown that polyhydroxylated flavonoids such as quercetin and genistein can inhibit tumor cell growth in vitro, and preliminary in vivo studies of the flavone L86-8275 have shown growth inhibition of LX529 and A549 lung carcinomas. L86-8275 [(-)cis-5,7-dihydroxy-2-(2-chlorophenyl)-8[4-(3-hydroxy-1-methyl)- piperidinyl]-4H-1-benzopyran-4-one] is a flavone of novel structure. The purpose of this study was to determine in vitro whether L86-8275 is a more potent inhibitor of growth in breast carcinoma and lung carcinoma cells than quercetin or genistein. We studied the effects of L86-8275 on cell growth in seven breast carcinoma cell lines and five lung carcinoma cell lines. MDA468 breast carcinoma was then selected for further study. Cell proliferation was measured by a colorimetric dye reduction assay; synthesis of DNA, RNA, and protein by incorporation of the radioactive metabolic precursors thymidine, uridine, or leucine, respectively; adenosine triphosphate (ATP) content by a luciferase-mediated bioluminescence reaction; and cell cycle progression by the use of cell-synchronizing drugs (aphidicolin and nocodazole) and flow cytometry. L86-8275 was not cytotoxic to stationary-phase cells but reversibly inhibited the growth of cells in exponential growth phase. At concentrations of 25-160 nM, L86-8275 inhibited growth of human breast and lung carcinoma cell lines by 50%. MDA468 breast carcinoma cells were 60-fold and 400-fold more sensitive to L86-8275 than to quercetin and genistein, respectively. By 24 hours after addition of L86-8275, DNA synthesis in MDA468 cells was inhibited by greater than 95%, protein synthesis by 80%, and RNA synthesis by 40%-60%, under conditions that preserved cellular ATP levels at approximately 80%-90% of control values. When MDA468 cells released from aphidicolin-induced cell cycle arrest were exposed to 200 nM L86-8275, they completed the S phase but arrested in G2. When cells released from nocodazole-induced cell cycle arrest were exposed to 200 nM L86-8275, they completed mitosis but arrested in G1. L86-8275 is a potent, yet reversible, growth-inhibitory flavone that can selectively block cell cycle progression in vitro at more than one point in the cell cycle. These findings suggest that L86-8275 is a candidate for further preclinical development, as well as a model for the synthesis of other flavonoids that might potently delay cell cycle progression to achieve inhibition of tumor growth. Future studies need to address optimal schedules for antiproliferative activity in vivo and inhibition of clonogenic activity."} {"id": "PMID:1279188", "title": "Basic fibroblast growth factor in the hypoglossal system: specific retrograde transport, trophic, and lesion-related responses.", "content": "To further clarify the function of basic fibroblast growth factor (bFGF) in the nervous system, we have examined its distribution, lesion-dependent regulation, retrograde transport, and trophic roles on rat hypoglossal neurons. In adult rats, bFGF-like immunoreactivity is localized in hypoglossal motoneurons, drastically reduced 2 days after axotomy, and re-expressed by 11 days. Neuron numbers and morphology assessed by Nissl staining are not affected by the lesion. 125J bFGF is specifically retrogradely transported by hypoglossal motoneurons from their peripheral nerve terminals. Moreover, bFGF stimulates the in vitro survival of hypoglossal neurons (ED50 2 ng/ml). In vivo administration of bFGF prevents lesion-induced motoneuron death to 14% in 7 day old rats and to 60% in 18 day old rats, but not the axotomy-induced decrease of choline acetyltransferase activity in the hypoglossal nucleus of adult rats. These results are consistent with a neurotrophic role of bFGF in the hypoglossal system.", "contents": "Basic fibroblast growth factor in the hypoglossal system: specific retrograde transport, trophic, and lesion-related responses. To further clarify the function of basic fibroblast growth factor (bFGF) in the nervous system, we have examined its distribution, lesion-dependent regulation, retrograde transport, and trophic roles on rat hypoglossal neurons. In adult rats, bFGF-like immunoreactivity is localized in hypoglossal motoneurons, drastically reduced 2 days after axotomy, and re-expressed by 11 days. Neuron numbers and morphology assessed by Nissl staining are not affected by the lesion. 125J bFGF is specifically retrogradely transported by hypoglossal motoneurons from their peripheral nerve terminals. Moreover, bFGF stimulates the in vitro survival of hypoglossal neurons (ED50 2 ng/ml). In vivo administration of bFGF prevents lesion-induced motoneuron death to 14% in 7 day old rats and to 60% in 18 day old rats, but not the axotomy-induced decrease of choline acetyltransferase activity in the hypoglossal nucleus of adult rats. These results are consistent with a neurotrophic role of bFGF in the hypoglossal system."} {"id": "PMID:1279189", "title": "Expression of p75NGFR TrkA, and TrkB mRNA in rat C6 glioma and type I astrocyte cultures.", "content": "Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) we have investigated the expression of the neurotrophin receptors p75NGFR, trkA, and trkB mRNAs in cultures of rat pup type I astrocytes and in the C6 rat glioma cell line. All three neurotrophin receptor mRNAs are expressed in both C6 cells and in type I astrocytic cultures. p75NGFR mRNA levels are increased by either cycloheximide or nerve growth factor (NGF) treatment of C6 cells as measured using RT-PCR. Type I astrocyte cultures also expressed p75NGFR mRNA and NGF treatment increased p75NGFR mRNA levels in these cultures. TrkB mRNA levels were increased by cycloheximide treatment of type I astrocyte cultures but not by NGF treatment. Using RT-PCR, trkA mRNA was detected in astrocytic cultures as well as in the rat C6 and PC-12 cell lines. We conclude that cultures of type I astrocytes express active NGF receptors and that glia can elicit a response to NGF as seen by an increase in p75NGFR mRNA levels following exposure to NGF.", "contents": "Expression of p75NGFR TrkA, and TrkB mRNA in rat C6 glioma and type I astrocyte cultures. Using a quantitative reverse transcription-polymerase chain reaction (RT-PCR) we have investigated the expression of the neurotrophin receptors p75NGFR, trkA, and trkB mRNAs in cultures of rat pup type I astrocytes and in the C6 rat glioma cell line. All three neurotrophin receptor mRNAs are expressed in both C6 cells and in type I astrocytic cultures. p75NGFR mRNA levels are increased by either cycloheximide or nerve growth factor (NGF) treatment of C6 cells as measured using RT-PCR. Type I astrocyte cultures also expressed p75NGFR mRNA and NGF treatment increased p75NGFR mRNA levels in these cultures. TrkB mRNA levels were increased by cycloheximide treatment of type I astrocyte cultures but not by NGF treatment. Using RT-PCR, trkA mRNA was detected in astrocytic cultures as well as in the rat C6 and PC-12 cell lines. We conclude that cultures of type I astrocytes express active NGF receptors and that glia can elicit a response to NGF as seen by an increase in p75NGFR mRNA levels following exposure to NGF."} {"id": "PMID:1279190", "title": "Differential expression of cytochrome oxidase (COX) genes in different regions of monkey brain.", "content": "A frontal pole cDNA library from monkey (Macaca mulatta) brain was screened to identify mRNAs that are expressed more in frontal pole as compared to primary visual cortex. Three cDNA clones, whose greater expression was confirmed by Northern blot analysis, were identified as cytochrome oxidase (COX) subunits I, II, and III (COX I, II, and III). Each clone showed higher levels of mRNA in the frontal pole, dorsal lateral prefrontal cortex, and hippocampus than in the primary visual or somatosensory cortices. COX histochemistry of prefrontal, visual, and somatosensory cortical regions demonstrated heterogeneous distributions, with highest activity in dendrite-rich neuropil of the cortex. A laminar distribution of COX mRNA expression also was demonstrated with in situ hybridization. mRNA was detected in cell bodies and in apical dendrites. These results indicate region specific differences in the distribution of COX activity and in the corresponding mRNA for three of its subunits within the monkey brain. Such differences may be related to differences in the distribution of neuropil as compared with cell bodies among the brain regions studied, and may be relevant to selective vulnerability in Alzheimer's disease.", "contents": "Differential expression of cytochrome oxidase (COX) genes in different regions of monkey brain. A frontal pole cDNA library from monkey (Macaca mulatta) brain was screened to identify mRNAs that are expressed more in frontal pole as compared to primary visual cortex. Three cDNA clones, whose greater expression was confirmed by Northern blot analysis, were identified as cytochrome oxidase (COX) subunits I, II, and III (COX I, II, and III). Each clone showed higher levels of mRNA in the frontal pole, dorsal lateral prefrontal cortex, and hippocampus than in the primary visual or somatosensory cortices. COX histochemistry of prefrontal, visual, and somatosensory cortical regions demonstrated heterogeneous distributions, with highest activity in dendrite-rich neuropil of the cortex. A laminar distribution of COX mRNA expression also was demonstrated with in situ hybridization. mRNA was detected in cell bodies and in apical dendrites. These results indicate region specific differences in the distribution of COX activity and in the corresponding mRNA for three of its subunits within the monkey brain. Such differences may be related to differences in the distribution of neuropil as compared with cell bodies among the brain regions studied, and may be relevant to selective vulnerability in Alzheimer's disease."} {"id": "PMID:1279191", "title": "Multiple intracellular signaling pathways of the neuropeptide substance P receptor.", "content": "The rat substance P (SP) receptor cDNA has been transfected into cultured rat KNRK cells, and a stable cell line expressing functional SP receptors established. Upon stimulation with SP, these cells responded by simultaneously activating two signaling pathways: the mobilization of intracellular Ca2+ and the raising of cyclic adenosine triphosphate (cAMP) levels. Both Ca2+ and cAMP responses were elicited in a similar dose-dependent manner with half maximal concentrations of approximately 5 x 10(-10) M. Following ionomycin treatment SP-dependent Ca2+ responses were abolished, whereas cAMP responses were preserved. Forskolin eliminated the SP-dependent cAMP elevation, however, the SP-induced Ca2+ mobilization remained unchanged. Furthermore, treatment with phorbol esters had no significant effect on either of the two SP-induced responses. Thus it appears that the SP receptor is capable of independently activating Ca2+ mobilization and cAMP pathways. These results may provide new insights for further understanding the diverse activities of SP in various systems in vitro and in vivo.", "contents": "Multiple intracellular signaling pathways of the neuropeptide substance P receptor. The rat substance P (SP) receptor cDNA has been transfected into cultured rat KNRK cells, and a stable cell line expressing functional SP receptors established. Upon stimulation with SP, these cells responded by simultaneously activating two signaling pathways: the mobilization of intracellular Ca2+ and the raising of cyclic adenosine triphosphate (cAMP) levels. Both Ca2+ and cAMP responses were elicited in a similar dose-dependent manner with half maximal concentrations of approximately 5 x 10(-10) M. Following ionomycin treatment SP-dependent Ca2+ responses were abolished, whereas cAMP responses were preserved. Forskolin eliminated the SP-dependent cAMP elevation, however, the SP-induced Ca2+ mobilization remained unchanged. Furthermore, treatment with phorbol esters had no significant effect on either of the two SP-induced responses. Thus it appears that the SP receptor is capable of independently activating Ca2+ mobilization and cAMP pathways. These results may provide new insights for further understanding the diverse activities of SP in various systems in vitro and in vivo."} {"id": "PMID:1279192", "title": "Studies on monoclonal anti-isotypic and anti-idiotypic antibodies against leukemia and myeloma: IV. Modulation of membrane fluidity of leukemic cell lines and tonsillar cell stimulated with McAbs.", "content": "In this study the technique of labelling the cell membrane with DPH fluorescence polarization was used to observe the membrane fluidity of B lymphocytic cell lines and tonsillar cells from healthy persons; the modulation effect on membrane fluidity induced by McAbs against isotypic and idiotypic determinants of IgM from patients with leukemia was studied as well. The expression of the corresponding isotypic and idiotypic determinants of IgM on the cell membrane was determined. The results show that the membrane fluidity of leukemic cell lines is remarkably higher than that of tonsillar cells from healthy persons, and McAbs against isotypic determinants of leukemic IgM can enhance the membrane fluidity of all kinds of cells mentioned above. However, the anti-idiotypic monoclonal antibody increased only the membrane fluidity of leukemic cell lines. These results indicated that there was a close relationship between the effect of McAbs on cell membrane fluidity and the expression of corresponding isotypic and idiotypic determinants of IgM on the cell membrane.", "contents": "Studies on monoclonal anti-isotypic and anti-idiotypic antibodies against leukemia and myeloma: IV. Modulation of membrane fluidity of leukemic cell lines and tonsillar cell stimulated with McAbs. In this study the technique of labelling the cell membrane with DPH fluorescence polarization was used to observe the membrane fluidity of B lymphocytic cell lines and tonsillar cells from healthy persons; the modulation effect on membrane fluidity induced by McAbs against isotypic and idiotypic determinants of IgM from patients with leukemia was studied as well. The expression of the corresponding isotypic and idiotypic determinants of IgM on the cell membrane was determined. The results show that the membrane fluidity of leukemic cell lines is remarkably higher than that of tonsillar cells from healthy persons, and McAbs against isotypic determinants of leukemic IgM can enhance the membrane fluidity of all kinds of cells mentioned above. However, the anti-idiotypic monoclonal antibody increased only the membrane fluidity of leukemic cell lines. These results indicated that there was a close relationship between the effect of McAbs on cell membrane fluidity and the expression of corresponding isotypic and idiotypic determinants of IgM on the cell membrane."} {"id": "PMID:1279193", "title": "Enhancement of B cell responses by the interaction of CD2 with LFA-3.", "content": "Potential effect of the interaction of CD2 with its ligand LFA-3 on B cell responses in vitro was studied to evaluate the action of CD2-LFA-3 in immune responses. It was found that: 1) addition of autologous erythrocytes to unfractional mononuclear cells resulted in enhancement of PWM-induced lymphocyte proliferation, and had no significant influence on non-mitogen stimulation; 2) autologous erythrocytes potentiated the synthesis of immunoglobulins; and 3) costimulating effects of autologous RBC can be depressed by preincubation of PBMNC with anti-CD2 monoclonal antibody (WuTll). The results suggest that preincubation of mononuclear cells with anti-CD2 McAb has a down-regulating effects on B cell responses and the interaction of CD2 with its ligand LFA-3 expressed by RBC is closely related to immune responses.", "contents": "Enhancement of B cell responses by the interaction of CD2 with LFA-3. Potential effect of the interaction of CD2 with its ligand LFA-3 on B cell responses in vitro was studied to evaluate the action of CD2-LFA-3 in immune responses. It was found that: 1) addition of autologous erythrocytes to unfractional mononuclear cells resulted in enhancement of PWM-induced lymphocyte proliferation, and had no significant influence on non-mitogen stimulation; 2) autologous erythrocytes potentiated the synthesis of immunoglobulins; and 3) costimulating effects of autologous RBC can be depressed by preincubation of PBMNC with anti-CD2 monoclonal antibody (WuTll). The results suggest that preincubation of mononuclear cells with anti-CD2 McAb has a down-regulating effects on B cell responses and the interaction of CD2 with its ligand LFA-3 expressed by RBC is closely related to immune responses."} {"id": "PMID:1279194", "title": "The receptor for mouse hepatitis virus in the resistant mouse strain SJL is functional: implications for the requirement of a second factor for viral infection.", "content": "The SJL mouse strain is resistant to infection by some strains of the murine coronavirus mouse hepatitis virus (MHV), such as JHM and A59. The block to virus infection has been variously attributed to defects in virus receptors or virus spread. Since the cellular receptors for MHV, mmCGM1 and mmCGM2, have recently been identified as members of the carcinoembryonic antigen family, we reexamined the possible defectiveness of the MHV receptors in SJL mouse strain. Cloning and sequencing of the cDNAs of both mmCGMs RNAs from SJL mice revealed that they were identical in size to those of the susceptible C57BL/6 (B6) mouse. There was some sequence divergence in the N terminus of the mmCGM molecules between the two mouse strains, resulting in a different number of potential glycosylation sites. This was confirmed by in vitro translation of the mmCGM RNAs, which showed that the glycosylated mmCGM2 of SJL was smaller than that of B6 mice. However, transfection of either mmCGM1 or mmCGM2 from SJL mice into MHV-resistant Cos 7 cells rendered the cells susceptible to MHV infection. The ability of the SJL mmCGM molecules to serve as MHV receptors was comparable to that of those from B6. These molecules are expressed in SJL mouse brain and liver in a similar ratio and in amounts equivalent to those in the B6 mouse. Furthermore, we demonstrated that an SJL-derived cell line was susceptible to A59 but resistant to JHM infection. We concluded that the MHV receptor molecules in the SJL mouse are functional and that the resistance of SJL mice to infection by some MHV strains most likely results from some other factor(s) required for virus entry or some other step(s) in virus replication.", "contents": "The receptor for mouse hepatitis virus in the resistant mouse strain SJL is functional: implications for the requirement of a second factor for viral infection. The SJL mouse strain is resistant to infection by some strains of the murine coronavirus mouse hepatitis virus (MHV), such as JHM and A59. The block to virus infection has been variously attributed to defects in virus receptors or virus spread. Since the cellular receptors for MHV, mmCGM1 and mmCGM2, have recently been identified as members of the carcinoembryonic antigen family, we reexamined the possible defectiveness of the MHV receptors in SJL mouse strain. Cloning and sequencing of the cDNAs of both mmCGMs RNAs from SJL mice revealed that they were identical in size to those of the susceptible C57BL/6 (B6) mouse. There was some sequence divergence in the N terminus of the mmCGM molecules between the two mouse strains, resulting in a different number of potential glycosylation sites. This was confirmed by in vitro translation of the mmCGM RNAs, which showed that the glycosylated mmCGM2 of SJL was smaller than that of B6 mice. However, transfection of either mmCGM1 or mmCGM2 from SJL mice into MHV-resistant Cos 7 cells rendered the cells susceptible to MHV infection. The ability of the SJL mmCGM molecules to serve as MHV receptors was comparable to that of those from B6. These molecules are expressed in SJL mouse brain and liver in a similar ratio and in amounts equivalent to those in the B6 mouse. Furthermore, we demonstrated that an SJL-derived cell line was susceptible to A59 but resistant to JHM infection. We concluded that the MHV receptor molecules in the SJL mouse are functional and that the resistance of SJL mice to infection by some MHV strains most likely results from some other factor(s) required for virus entry or some other step(s) in virus replication."} {"id": "PMID:1279195", "title": "Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region.", "content": "Neutralizing antibodies that recognize the human immunodeficiency virus gp120 exterior envelope glycoprotein and are directed against either the third variable (V3) loop or conserved, discontinuous epitopes overlapping the CD4 binding region have been described. Here we report several observations that suggest a structural relationship between the V3 loop and amino acids in the fourth conserved (C4) gp120 region that constitute part of the CD4 binding site and the conserved neutralization epitopes. Treatment of the gp120 glycoprotein with ionic detergents resulted in a V3 loop-dependent masking of both linear C4 epitopes and discontinuous neutralization epitopes overlapping the CD4 binding site. Increased recognition of the native gp120 glycoprotein by an anti-V3 loop monoclonal antibody, 9284, resulted from from single amino acid changes either in the base of the V3 loop or in the gp120 C4 region. These amino acid changes also resulted in increased exposure of conserved epitopes overlapping the CD4 binding region. The replication-competent subset of these mutants exhibited increased sensitivity to neutralization by antibody 9284 and anti-CD4 binding site antibodies. The implied relationship of the V3 loop, which mediates post-receptor binding steps in virus entry, and components of the CD4 binding region may be important for the interaction of these functional gp120 domains and for the observed cooperativity of neutralizing antibodies directed against these regions.", "contents": "Relationship of the human immunodeficiency virus type 1 gp120 third variable loop to a component of the CD4 binding site in the fourth conserved region. Neutralizing antibodies that recognize the human immunodeficiency virus gp120 exterior envelope glycoprotein and are directed against either the third variable (V3) loop or conserved, discontinuous epitopes overlapping the CD4 binding region have been described. Here we report several observations that suggest a structural relationship between the V3 loop and amino acids in the fourth conserved (C4) gp120 region that constitute part of the CD4 binding site and the conserved neutralization epitopes. Treatment of the gp120 glycoprotein with ionic detergents resulted in a V3 loop-dependent masking of both linear C4 epitopes and discontinuous neutralization epitopes overlapping the CD4 binding site. Increased recognition of the native gp120 glycoprotein by an anti-V3 loop monoclonal antibody, 9284, resulted from from single amino acid changes either in the base of the V3 loop or in the gp120 C4 region. These amino acid changes also resulted in increased exposure of conserved epitopes overlapping the CD4 binding region. The replication-competent subset of these mutants exhibited increased sensitivity to neutralization by antibody 9284 and anti-CD4 binding site antibodies. The implied relationship of the V3 loop, which mediates post-receptor binding steps in virus entry, and components of the CD4 binding region may be important for the interaction of these functional gp120 domains and for the observed cooperativity of neutralizing antibodies directed against these regions."} {"id": "PMID:1279196", "title": "Antigenic sequences of poliovirus recognized by T cells: serotype-specific epitopes on VP1 and VP3 and cross-reactive epitopes on VP4 defined by using CD4+ T-cell clones.", "content": "A panel of poliovirus-specific murine CD4+ T-cell clones has been established from both BALB/c (H-2d) and CBA (H-2k) mice immunized with Sabin vaccine strains of poliovirus serotype 1, 2, or 3. T-cell clones were found to be either serotype specific or cross-reactive between two or all three serotypes. Specificity analysis against purified poliovirus proteins demonstrated that T-cell clones recognized determinants on the surface capsid proteins VP1, VP2, and VP3 and the internal capsid protein VP4. Panels of overlapping synthetic peptides were used to identify eight distinct T-cell epitopes. One type 3-specific T-cell clone recognized an epitope within amino acids 257 and 264 of VP1. Three T-cell epitopes corresponding to residues 14 to 28, 189 to 203, and 196 to 210 were identified on VP3 of poliovirus type 2. The remaining four T-cell epitopes were mapped to an immunodominant region of VP4, encompassed within residues 6 and 35 and recognized by both H-2d and H-2k mice. The epitopes on VP4 were conserved between serotypes, and this may account for the predominantly cross-reactive poliovirus-specific T-cell response observed with polyclonal T-cell populations. In contrast, T-cell clones that recognize epitopes on VP1 or VP3 were largely serotype specific; single or multiple amino acid substitutions were found to be critical for T-cell recognition.", "contents": "Antigenic sequences of poliovirus recognized by T cells: serotype-specific epitopes on VP1 and VP3 and cross-reactive epitopes on VP4 defined by using CD4+ T-cell clones. A panel of poliovirus-specific murine CD4+ T-cell clones has been established from both BALB/c (H-2d) and CBA (H-2k) mice immunized with Sabin vaccine strains of poliovirus serotype 1, 2, or 3. T-cell clones were found to be either serotype specific or cross-reactive between two or all three serotypes. Specificity analysis against purified poliovirus proteins demonstrated that T-cell clones recognized determinants on the surface capsid proteins VP1, VP2, and VP3 and the internal capsid protein VP4. Panels of overlapping synthetic peptides were used to identify eight distinct T-cell epitopes. One type 3-specific T-cell clone recognized an epitope within amino acids 257 and 264 of VP1. Three T-cell epitopes corresponding to residues 14 to 28, 189 to 203, and 196 to 210 were identified on VP3 of poliovirus type 2. The remaining four T-cell epitopes were mapped to an immunodominant region of VP4, encompassed within residues 6 and 35 and recognized by both H-2d and H-2k mice. The epitopes on VP4 were conserved between serotypes, and this may account for the predominantly cross-reactive poliovirus-specific T-cell response observed with polyclonal T-cell populations. In contrast, T-cell clones that recognize epitopes on VP1 or VP3 were largely serotype specific; single or multiple amino acid substitutions were found to be critical for T-cell recognition."} {"id": "PMID:1279197", "title": "Mutational analysis of the major homology region of Mason-Pfizer monkey virus by use of saturation mutagenesis.", "content": "The major capsid (CA) protein of retroviruses possesses a stretch of 20 amino acids, called the major homology region (MHR), which is evolutionarily conserved and invariant in location within the primary sequence of the protein. The function of this region was investigated by examining the effect of random single-amino-acid substitutions within the central 13 positions of the MHR on the life cycle of Mason-Pfizer monkey virus (M-PMV), an immunosuppressive D-type retrovirus. When these mutants were subcloned into an M-PMV proviral vector and expressed in COS cells, one of two major phenotypes was observed. The first group, containing three mutants bearing drastic amino acid substitutions, was unable to assemble capsids in the cytoplasm of the host cell. The second and more common group of mutants was able to assemble and release virions, but these either displayed greatly reduced levels of infectivity or were completely noninfectious. Included within this second group were two mutants with unusual phenotypes; mutant D158Y exhibited a novel cleavage site for the viral protease that resulted in cleavage of the major capsid protein, p27 (CA), within the MHR, whereas mutant F156L appeared to have lost a major site for antibody recognition within the mature CA protein. The results of this mutagenic analysis suggest that changes in the MHR sequence can interfere with the assembly of viral capsids and block an early stage of the infection cycle of M-PMV.", "contents": "Mutational analysis of the major homology region of Mason-Pfizer monkey virus by use of saturation mutagenesis. The major capsid (CA) protein of retroviruses possesses a stretch of 20 amino acids, called the major homology region (MHR), which is evolutionarily conserved and invariant in location within the primary sequence of the protein. The function of this region was investigated by examining the effect of random single-amino-acid substitutions within the central 13 positions of the MHR on the life cycle of Mason-Pfizer monkey virus (M-PMV), an immunosuppressive D-type retrovirus. When these mutants were subcloned into an M-PMV proviral vector and expressed in COS cells, one of two major phenotypes was observed. The first group, containing three mutants bearing drastic amino acid substitutions, was unable to assemble capsids in the cytoplasm of the host cell. The second and more common group of mutants was able to assemble and release virions, but these either displayed greatly reduced levels of infectivity or were completely noninfectious. Included within this second group were two mutants with unusual phenotypes; mutant D158Y exhibited a novel cleavage site for the viral protease that resulted in cleavage of the major capsid protein, p27 (CA), within the MHR, whereas mutant F156L appeared to have lost a major site for antibody recognition within the mature CA protein. The results of this mutagenic analysis suggest that changes in the MHR sequence can interfere with the assembly of viral capsids and block an early stage of the infection cycle of M-PMV."} {"id": "PMID:1279198", "title": "Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine.", "content": "We have used the technique of in vitro selection to generate variants of human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxyinosine (ddI) and cross-resistant to 2',3'-dideoxycytidine (ddC). The complete reverse transcriptase (RT)-coding regions, plus portions of flanking sequences, of viruses possessing a ddI-resistant phenotype were cloned and sequenced by polymerase chain reaction (PCR)-based methods. We observed that several of these viruses possessed mutations at amino acid sites 184 (Met-->Val; ATG-->GTG) and 294 (Pro-->Ser; CCA-->TCA). These mutations were introduced in the pol gene of infectious, cloned HXB2-D DNA by site-directed mutagenesis. Viral replication assays confirmed the importance of site 184 with regard to resistance to ddI. The recombinant viruses thus generated displayed more than fivefold-greater resistance to ddI than parental HXB2-D did. Moreover, more than fivefold-greater resistance to ddC was also documented; however, the recombinant viruses continued to be inhibited by zidovudine (AZT). No resistance to ddI, ddC, or AZT was introduced by inclusion of mutation site 294 in the pol gene of HXB2-D. PCR analysis performed on viral samples obtained from patients receiving long-term ddI therapy confirmed the presence of mutation site 184 in five of seven cases tested. In three of these five positive cases, the wild-type codon was also detected, indicating that mixtures of viral quasispecies were apparently present. Viruses possessing a ddI resistance phenotype were isolated from both subjects whose viruses contained only the mutated rather than wild-type codon at position 184 as well as from a third individual, whose viruses appeared to be mostly of the mutated variety.", "contents": "Novel mutation in the human immunodeficiency virus type 1 reverse transcriptase gene that encodes cross-resistance to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. We have used the technique of in vitro selection to generate variants of human immunodeficiency virus type 1 (HIV-1) that are resistant to 2',3'-dideoxyinosine (ddI) and cross-resistant to 2',3'-dideoxycytidine (ddC). The complete reverse transcriptase (RT)-coding regions, plus portions of flanking sequences, of viruses possessing a ddI-resistant phenotype were cloned and sequenced by polymerase chain reaction (PCR)-based methods. We observed that several of these viruses possessed mutations at amino acid sites 184 (Met-->Val; ATG-->GTG) and 294 (Pro-->Ser; CCA-->TCA). These mutations were introduced in the pol gene of infectious, cloned HXB2-D DNA by site-directed mutagenesis. Viral replication assays confirmed the importance of site 184 with regard to resistance to ddI. The recombinant viruses thus generated displayed more than fivefold-greater resistance to ddI than parental HXB2-D did. Moreover, more than fivefold-greater resistance to ddC was also documented; however, the recombinant viruses continued to be inhibited by zidovudine (AZT). No resistance to ddI, ddC, or AZT was introduced by inclusion of mutation site 294 in the pol gene of HXB2-D. PCR analysis performed on viral samples obtained from patients receiving long-term ddI therapy confirmed the presence of mutation site 184 in five of seven cases tested. In three of these five positive cases, the wild-type codon was also detected, indicating that mixtures of viral quasispecies were apparently present. Viruses possessing a ddI resistance phenotype were isolated from both subjects whose viruses contained only the mutated rather than wild-type codon at position 184 as well as from a third individual, whose viruses appeared to be mostly of the mutated variety."} {"id": "PMID:1279199", "title": "Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines.", "content": "Increased levels of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, have been detected in specimens from human immunodeficiency virus type 1 (HIV-1)-infected individuals. Here we demonstrate that HIV-1 activates the expression of TNF but not of IL-1 and IL-6 in acutely and chronically infected T cells. The increase in TNF gene expression is due to activation of the TNF promoter by the viral gene product Tat. Transactivation of TNF gene expression requires the product of the first exon of the tat gene and is cell type independent. T cells chronically infected with pol-defective HIV-1 provirus constitutively express both Tat and TNF at levels significantly higher (fivefold) than those seen in control cells, and treatment with phorbol myristate acetate greatly enhances Tat expression and TNF production. As TNF can increase the production of IL-1 and IL-6 and these inflammatory cytokines all enhance HIV-1 gene expression and affect the immune, vascular, and central nervous systems, the activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses viral products and host factors to increase its own expression and infectivity and to induce disease.", "contents": "Effects of the human immunodeficiency virus type 1 Tat protein on the expression of inflammatory cytokines. Increased levels of inflammatory cytokines, including tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6, have been detected in specimens from human immunodeficiency virus type 1 (HIV-1)-infected individuals. Here we demonstrate that HIV-1 activates the expression of TNF but not of IL-1 and IL-6 in acutely and chronically infected T cells. The increase in TNF gene expression is due to activation of the TNF promoter by the viral gene product Tat. Transactivation of TNF gene expression requires the product of the first exon of the tat gene and is cell type independent. T cells chronically infected with pol-defective HIV-1 provirus constitutively express both Tat and TNF at levels significantly higher (fivefold) than those seen in control cells, and treatment with phorbol myristate acetate greatly enhances Tat expression and TNF production. As TNF can increase the production of IL-1 and IL-6 and these inflammatory cytokines all enhance HIV-1 gene expression and affect the immune, vascular, and central nervous systems, the activation of TNF by Tat may be part of a complex pathway in which HIV-1 uses viral products and host factors to increase its own expression and infectivity and to induce disease."} {"id": "PMID:1279200", "title": "Characterization of reticuloendotheliosis virus-transformed avian T-lymphoblastoid cell lines infected with Marek's disease virus.", "content": "The expression of Marek's disease virus (MDV) transcripts and protein products was investigated in reticuloendotheliosis virus-transformed avian T-lymphoblastoid cell line RECC-CU91, which was superinfected with MDV. The presence of MDV in the superinfected cell line, renamed RECC-CU210, was demonstrated by Southern hybridization with 32P-labeled BamHI-H and -B fragments of the BamHI MDV DNA library. Examination of RECC-CU210 for the expression of MDV-specific RNA transcripts encoded by the internal repeat long (IRL), internal repeat short (IRS), and unique short (US) regions of the MDV genome revealed two small transcripts of 0.6 and 0.7 kb. These transcripts were mapped to the IRL and IRS regions, respectively. In contrast, RECC-CU211, which was developed through transfection of CU210 with the BamHI-A fragment of MDV, expressed an additional nine transcripts from the IRL, IRS, and US regions. CU211 but not CU210 also expressed a complex of polypeptides of 40, 38, and 24 kDa, identified by monoclonal antibodies as MDV-specific phosphoproteins. The 38-kDa phosphoprotein is likely to be pp38, an early viral protein that maps within the IRL region of the MDV genome. These findings suggest that genes located within the transfected BamHI-A fragment transactivated a number of genes located in the IRL region of the MDV genome.", "contents": "Characterization of reticuloendotheliosis virus-transformed avian T-lymphoblastoid cell lines infected with Marek's disease virus. The expression of Marek's disease virus (MDV) transcripts and protein products was investigated in reticuloendotheliosis virus-transformed avian T-lymphoblastoid cell line RECC-CU91, which was superinfected with MDV. The presence of MDV in the superinfected cell line, renamed RECC-CU210, was demonstrated by Southern hybridization with 32P-labeled BamHI-H and -B fragments of the BamHI MDV DNA library. Examination of RECC-CU210 for the expression of MDV-specific RNA transcripts encoded by the internal repeat long (IRL), internal repeat short (IRS), and unique short (US) regions of the MDV genome revealed two small transcripts of 0.6 and 0.7 kb. These transcripts were mapped to the IRL and IRS regions, respectively. In contrast, RECC-CU211, which was developed through transfection of CU210 with the BamHI-A fragment of MDV, expressed an additional nine transcripts from the IRL, IRS, and US regions. CU211 but not CU210 also expressed a complex of polypeptides of 40, 38, and 24 kDa, identified by monoclonal antibodies as MDV-specific phosphoproteins. The 38-kDa phosphoprotein is likely to be pp38, an early viral protein that maps within the IRL region of the MDV genome. These findings suggest that genes located within the transfected BamHI-A fragment transactivated a number of genes located in the IRL region of the MDV genome."} {"id": "PMID:1279201", "title": "Isolation and characterization of cDNAs from BamHI-H gene family RNAs associated with the tumorigenicity of Marek's disease virus.", "content": "It has been reported that loss of the tumorigenic potential of attenuated Marek's disease virus (MDV) is strongly associated with amplification of the 132-bp repeat sequences found within the BamHI-D and BamHI-H fragments contained within the long terminal repeat and the long internal repeat, respectively. The expansion of this region results in loss of transcripts that are 3.8, 3.0, and 1.8 kbp long that are produced by tumorigenic strains of MDV. This evidence suggests that production of one or more of these three RNAs is strongly associated with the tumorigenic potential of the virus. In this study, we have cloned and sequenced 1.69-, 1.5-, 1.9-, and 2.2-kbp cDNAs from the BamHI-H gene family RNAs associated with tumorigenicity. The 1.69- and 2.2-kbp cDNAs are derived from nonspliced transcripts, whereas the 1.5- and 1.9-kbp cDNAs are from single spliced mRNAs spanning the BamHI-H and BamHI-I2 fragments of MDV DNA. Sequence analysis has shown two potential open reading frames in each of the cDNAs. The putative 63-amino-acid protein encoded by the first open reading frame in the 1.69-kbp cDNA and a putative 75-amino-acid protein encoded by the first open reading frame in the 1.5-kbp cDNA showed limited homology with the mouse T-cell lymphoma oncogene and the fes/fps family of kinase-related transforming proteins.", "contents": "Isolation and characterization of cDNAs from BamHI-H gene family RNAs associated with the tumorigenicity of Marek's disease virus. It has been reported that loss of the tumorigenic potential of attenuated Marek's disease virus (MDV) is strongly associated with amplification of the 132-bp repeat sequences found within the BamHI-D and BamHI-H fragments contained within the long terminal repeat and the long internal repeat, respectively. The expansion of this region results in loss of transcripts that are 3.8, 3.0, and 1.8 kbp long that are produced by tumorigenic strains of MDV. This evidence suggests that production of one or more of these three RNAs is strongly associated with the tumorigenic potential of the virus. In this study, we have cloned and sequenced 1.69-, 1.5-, 1.9-, and 2.2-kbp cDNAs from the BamHI-H gene family RNAs associated with tumorigenicity. The 1.69- and 2.2-kbp cDNAs are derived from nonspliced transcripts, whereas the 1.5- and 1.9-kbp cDNAs are from single spliced mRNAs spanning the BamHI-H and BamHI-I2 fragments of MDV DNA. Sequence analysis has shown two potential open reading frames in each of the cDNAs. The putative 63-amino-acid protein encoded by the first open reading frame in the 1.69-kbp cDNA and a putative 75-amino-acid protein encoded by the first open reading frame in the 1.5-kbp cDNA showed limited homology with the mouse T-cell lymphoma oncogene and the fes/fps family of kinase-related transforming proteins."} {"id": "PMID:1279202", "title": "Creation and characterization of temperature-sensitive mutants of the lck tyrosine protein kinase.", "content": "Temperature-sensitive mutants of the lck tyrosine protein kinase were created by the introduction of mutations known to cause temperature sensitivity of the v-src tyrosine protein kinase of Rous sarcoma virus. p56lck activated by mutation of the regulatory site of tyrosine phosphorylation, Tyr-505, to Phe transforms fibroblasts in culture. Mutations identical to those responsible for the temperature-sensitive phenotypes of the tsNY68 and tsNY72-4 v-src mutants rendered this activated lck gene temperature sensitive for both morphological transformation and induction of growth in soft agar. The mutant proteins were incapable of cellular transformation at the nonpermissive temperature in part because of failure of the lck protein to accumulate to normal levels. Morphological transformation of fibroblasts was detectable within 24 h of a shift of cells to the permissive temperature and was essentially complete in 48 to 72 h. These mutants should prove useful for the study of the function of the lck kinase in hematopoietic cells.", "contents": "Creation and characterization of temperature-sensitive mutants of the lck tyrosine protein kinase. Temperature-sensitive mutants of the lck tyrosine protein kinase were created by the introduction of mutations known to cause temperature sensitivity of the v-src tyrosine protein kinase of Rous sarcoma virus. p56lck activated by mutation of the regulatory site of tyrosine phosphorylation, Tyr-505, to Phe transforms fibroblasts in culture. Mutations identical to those responsible for the temperature-sensitive phenotypes of the tsNY68 and tsNY72-4 v-src mutants rendered this activated lck gene temperature sensitive for both morphological transformation and induction of growth in soft agar. The mutant proteins were incapable of cellular transformation at the nonpermissive temperature in part because of failure of the lck protein to accumulate to normal levels. Morphological transformation of fibroblasts was detectable within 24 h of a shift of cells to the permissive temperature and was essentially complete in 48 to 72 h. These mutants should prove useful for the study of the function of the lck kinase in hematopoietic cells."} {"id": "PMID:1279203", "title": "Coronavirus species specificity: murine coronavirus binds to a mouse-specific epitope on its carcinoembryonic antigen-related receptor glycoprotein.", "content": "Like most coronaviruses, the coronavirus mouse hepatitis virus (MHV) exhibits strong species specificity, causing natural infection only in mice. MHV-A59 virions use as a receptor a 110- to 120-kDa glycoprotein (MHVR) in the carcinoembryonic antigen (CEA) family of glycoproteins (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G. S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; and R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). The role of virus-receptor interactions in determining the species specificity of MHV-A59 was examined by comparing the binding of virus and antireceptor antibodies to cell lines and intestinal brush border membranes (BBM) from many species. Polyclonal antireceptor antiserum (anti-MHVR) raised by immunization of SJL/J mice with BALB/c BBM recognized MHVR specifically in immunoblots of BALB/c BBM but not in BBM from adult SJL/J mice that are resistant to infection with MHV-A59, indicating a major difference in epitopes between MHVR and its SJL/J homolog which does not bind MHV (7). Anti-MHVR bound to plasma membranes of MHV-susceptible murine cell lines but not to membranes of human, cat, dog, monkey, or hamster cell lines. Cell lines from these species were resistant to MHV-A59 infection, and only the murine cell lines tested were susceptible. Pretreatment of murine fibroblasts with anti-MHVR prevented binding of radiolabeled virions to murine cells and prevented virus infection. Solid-phase virus-binding assays and virus overlay protein blot assays showed that MHV-A59 virions bound to MHVR on intestinal BBM from MHV-susceptible mouse strains but not to proteins on intestinal BBM from humans, cats, dogs, pigs, cows, rabbits, rats, cotton rats, or chickens. In immunoblots of BBM from these species, both polyclonal and monoclonal antireceptor antibodies that block MHV-A59 infection of murine cells recognized only the murine CEA-related glycoprotein and not homologous CEA-related glycoproteins of other species. These results suggest that MHV-A59 binds to a mouse-specific epitope of MHVR, and they support the hypothesis that the species specificity of MHV-A59 infection may be due to the specificity of the virus-receptor interaction.", "contents": "Coronavirus species specificity: murine coronavirus binds to a mouse-specific epitope on its carcinoembryonic antigen-related receptor glycoprotein. Like most coronaviruses, the coronavirus mouse hepatitis virus (MHV) exhibits strong species specificity, causing natural infection only in mice. MHV-A59 virions use as a receptor a 110- to 120-kDa glycoprotein (MHVR) in the carcinoembryonic antigen (CEA) family of glycoproteins (G. S. Dveksler, M. N. Pensiero, C. B. Cardellichio, R. K. Williams, G. S. Jiang, K. V. Holmes, and C. W. Dieffenbach, J. Virol. 65:6881-6891, 1991; and R. K. Williams, G. S. Jiang, and K. V. Holmes, Proc. Natl. Acad. Sci. USA 88:5533-5536, 1991). The role of virus-receptor interactions in determining the species specificity of MHV-A59 was examined by comparing the binding of virus and antireceptor antibodies to cell lines and intestinal brush border membranes (BBM) from many species. Polyclonal antireceptor antiserum (anti-MHVR) raised by immunization of SJL/J mice with BALB/c BBM recognized MHVR specifically in immunoblots of BALB/c BBM but not in BBM from adult SJL/J mice that are resistant to infection with MHV-A59, indicating a major difference in epitopes between MHVR and its SJL/J homolog which does not bind MHV (7). Anti-MHVR bound to plasma membranes of MHV-susceptible murine cell lines but not to membranes of human, cat, dog, monkey, or hamster cell lines. Cell lines from these species were resistant to MHV-A59 infection, and only the murine cell lines tested were susceptible. Pretreatment of murine fibroblasts with anti-MHVR prevented binding of radiolabeled virions to murine cells and prevented virus infection. Solid-phase virus-binding assays and virus overlay protein blot assays showed that MHV-A59 virions bound to MHVR on intestinal BBM from MHV-susceptible mouse strains but not to proteins on intestinal BBM from humans, cats, dogs, pigs, cows, rabbits, rats, cotton rats, or chickens. In immunoblots of BBM from these species, both polyclonal and monoclonal antireceptor antibodies that block MHV-A59 infection of murine cells recognized only the murine CEA-related glycoprotein and not homologous CEA-related glycoproteins of other species. These results suggest that MHV-A59 binds to a mouse-specific epitope of MHVR, and they support the hypothesis that the species specificity of MHV-A59 infection may be due to the specificity of the virus-receptor interaction."} {"id": "PMID:1279204", "title": "Distribution of conserved and specific epitopes on the VP8 subunit of rotavirus VP4.", "content": "Three cDNA clones comprising the VP8 subunit of the VP4 of human rotavirus strain KU (VP7 serotype G1; VP4 serotype P1A) G1 were constructed. The corresponding encoded peptides were designated according to their locations in the VP8 subunit as A (amino acids 1 to 102), B (amino acids 84 to 180), and C (amino acids 150 to 246 plus amino acids 247 to 251 from VP5). In addition, cDNA clones encoding peptide B of the VP8 subunit of the VP4 gene from human rotavirus strains DS-1 (G2; P1B) and 1076 (G2; P2) were also constructed. These DNA fragments were inserted into plasmid pGEMEX-1 and expressed in Escherichia coli. Western immunoblot analysis using antisera to rotavirus strains KU (P1A), Wa (P1A), DS-1 (P1B), 1076 (P2), and M37 (P2) demonstrated that peptides A and C cross-reacted with heterotypic human rotavirus VP4 antisera, suggesting that these two peptides represent conserved epitopes in the VP8 subunit. In contrast, peptide B appears to be involved in the VP4 serotype and subtype specificities, because it reacted only with the corresponding serotype- and subtype-specific antiserum. Antiserum raised against peptide A, B, or C of strain KU contained a lower level of neutralizing activity than did that induced by the entire VP8 subunit. In addition, the serotype-specific neutralizing activity of anti-KU VP8 serum was ablated after adsorption with the KU VP8 protein but not with a mixture of peptides A, B, and C of strain KU, suggesting that most of the serotype-specific epitopes in the VP8 subunit are conformational and are dependent on the entire amino acid sequence of VP8.", "contents": "Distribution of conserved and specific epitopes on the VP8 subunit of rotavirus VP4. Three cDNA clones comprising the VP8 subunit of the VP4 of human rotavirus strain KU (VP7 serotype G1; VP4 serotype P1A) G1 were constructed. The corresponding encoded peptides were designated according to their locations in the VP8 subunit as A (amino acids 1 to 102), B (amino acids 84 to 180), and C (amino acids 150 to 246 plus amino acids 247 to 251 from VP5). In addition, cDNA clones encoding peptide B of the VP8 subunit of the VP4 gene from human rotavirus strains DS-1 (G2; P1B) and 1076 (G2; P2) were also constructed. These DNA fragments were inserted into plasmid pGEMEX-1 and expressed in Escherichia coli. Western immunoblot analysis using antisera to rotavirus strains KU (P1A), Wa (P1A), DS-1 (P1B), 1076 (P2), and M37 (P2) demonstrated that peptides A and C cross-reacted with heterotypic human rotavirus VP4 antisera, suggesting that these two peptides represent conserved epitopes in the VP8 subunit. In contrast, peptide B appears to be involved in the VP4 serotype and subtype specificities, because it reacted only with the corresponding serotype- and subtype-specific antiserum. Antiserum raised against peptide A, B, or C of strain KU contained a lower level of neutralizing activity than did that induced by the entire VP8 subunit. In addition, the serotype-specific neutralizing activity of anti-KU VP8 serum was ablated after adsorption with the KU VP8 protein but not with a mixture of peptides A, B, and C of strain KU, suggesting that most of the serotype-specific epitopes in the VP8 subunit are conformational and are dependent on the entire amino acid sequence of VP8."} {"id": "PMID:1279205", "title": "Mutational analysis of the fingers domain of human immunodeficiency virus type 1 reverse transcriptase.", "content": "Using BspMI cassette vectors, we have constructed a series of mutations in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) that cause specific amino acid substitutions within the polymerase domain. The RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities of the mutant RTs were assayed. The elucidation of the structure of HIV-1 RT makes it possible to determine the locations of specific mutations in the three-dimensional structure of HIV-1 RT [E. Arnold, A. Jacobo-Molina, R. G. Nanni, R. L. Williams, X. Lu, J. Ding, A. D. Clark, Jr., A. Zhang, A. L. Ferris, P. Clark, A. Hizi, and S. H. Hughes, Nature (London) 357:85-89, 1992; L. A. Kohlstaedt, J. Wang, J. M. Friedman, P. A. Rice, and T. A. Steitz, Science 256:1783-1790, 1992]. The mutations described in this report are between amino acids 25 and 81, within the \"fingers\" domain of RT (Kohlstaedt et al., Science 256:1783-1790, 1992). It has been suggested that this domain may play a role in positioning the template. Although the fingers domain does not contain the active site for polymerization, several of the mutations within this domain disrupt polymerase activity without significantly affecting RNase H activity.", "contents": "Mutational analysis of the fingers domain of human immunodeficiency virus type 1 reverse transcriptase. Using BspMI cassette vectors, we have constructed a series of mutations in human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) that cause specific amino acid substitutions within the polymerase domain. The RNA-dependent DNA polymerase, DNA-dependent DNA polymerase, and RNase H activities of the mutant RTs were assayed. The elucidation of the structure of HIV-1 RT makes it possible to determine the locations of specific mutations in the three-dimensional structure of HIV-1 RT [E. Arnold, A. Jacobo-Molina, R. G. Nanni, R. L. Williams, X. Lu, J. Ding, A. D. Clark, Jr., A. Zhang, A. L. Ferris, P. Clark, A. Hizi, and S. H. Hughes, Nature (London) 357:85-89, 1992; L. A. Kohlstaedt, J. Wang, J. M. Friedman, P. A. Rice, and T. A. Steitz, Science 256:1783-1790, 1992]. The mutations described in this report are between amino acids 25 and 81, within the \"fingers\" domain of RT (Kohlstaedt et al., Science 256:1783-1790, 1992). It has been suggested that this domain may play a role in positioning the template. Although the fingers domain does not contain the active site for polymerization, several of the mutations within this domain disrupt polymerase activity without significantly affecting RNase H activity."} {"id": "PMID:1279206", "title": "Loss of infectivity by progeny virus from alpha interferon-treated human immunodeficiency virus type 1-infected T cells is associated with defective assembly of envelope gp120.", "content": "Levels of human immunodeficiency virus (HIV) DNA, RNA, or p24 antigen and reverse transcriptase activity in T-cell cultures treated with 500 IU of recombinant alpha interferon (rIFN alpha) per ml were comparable to those in control cultures. Radioimmunoprecipitation analysis of proteins in lysates of IFN-treated T cells documented a marked accumulation of HIV proteins. Localization of gp120 by immunofluorescence showed a diffuse pattern in IFN-treated cells quite distinct from the ring pattern in untreated control cells. That large quantities of gp120 in aberrant cell compartments might affect HIV morphogenesis was confirmed in infectivity studies: virions from IFN-treated cells were 100- to 1,000-fold less infectious than an equal number of virions from control cells. Direct examination of IFN-treated and control HIV-infected cells by transmission electron microscopy showed little difference in the number or distribution of viral particles. However, quantitation of gp120 by immunogold particle analysis revealed a marked depletion of envelope glycoprotein in virions released from IFN-treated cells. This defect in gp120 assembly onto mature viral particles provides a molecular basis for this loss of infectivity.", "contents": "Loss of infectivity by progeny virus from alpha interferon-treated human immunodeficiency virus type 1-infected T cells is associated with defective assembly of envelope gp120. Levels of human immunodeficiency virus (HIV) DNA, RNA, or p24 antigen and reverse transcriptase activity in T-cell cultures treated with 500 IU of recombinant alpha interferon (rIFN alpha) per ml were comparable to those in control cultures. Radioimmunoprecipitation analysis of proteins in lysates of IFN-treated T cells documented a marked accumulation of HIV proteins. Localization of gp120 by immunofluorescence showed a diffuse pattern in IFN-treated cells quite distinct from the ring pattern in untreated control cells. That large quantities of gp120 in aberrant cell compartments might affect HIV morphogenesis was confirmed in infectivity studies: virions from IFN-treated cells were 100- to 1,000-fold less infectious than an equal number of virions from control cells. Direct examination of IFN-treated and control HIV-infected cells by transmission electron microscopy showed little difference in the number or distribution of viral particles. However, quantitation of gp120 by immunogold particle analysis revealed a marked depletion of envelope glycoprotein in virions released from IFN-treated cells. This defect in gp120 assembly onto mature viral particles provides a molecular basis for this loss of infectivity."} {"id": "PMID:1279207", "title": "Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases: effects on nucleoside analog resistance.", "content": "A Glu-89-->Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). This residue was altered to Ala, Val, Ser, Thr, Gln, Asp, Asn, or Lys, and the ddGTP and PFA sensitivities of the mutant RTs were measured. Replacements with Ala, Gly, Val, and Thr led to resistance to inhibition by ddGTP, while mutants with amino acid Ser, Gln, Asn, Asp, or Lys displayed only moderate or no resistance. A similar result was obtained with inhibition by PFA, except that the Asp-89 mutant also displayed resistance. Furthermore, the introduction of Glu-89-->Gly alteration into the RT of human immunodeficiency virus type 2 likewise rendered it resistant to both ddGTP and PFA.", "contents": "Mutagenesis of the Glu-89 residue in human immunodeficiency virus type 1 (HIV-1) and HIV-2 reverse transcriptases: effects on nucleoside analog resistance. A Glu-89-->Gly alteration in the human immunodeficiency virus type 1 reverse transcriptase (RT) was previously shown to result in resistance to several dideoxynucleoside analogs and to phosphonoformic acid (PFA; foscarnet). This residue was altered to Ala, Val, Ser, Thr, Gln, Asp, Asn, or Lys, and the ddGTP and PFA sensitivities of the mutant RTs were measured. Replacements with Ala, Gly, Val, and Thr led to resistance to inhibition by ddGTP, while mutants with amino acid Ser, Gln, Asn, Asp, or Lys displayed only moderate or no resistance. A similar result was obtained with inhibition by PFA, except that the Asp-89 mutant also displayed resistance. Furthermore, the introduction of Glu-89-->Gly alteration into the RT of human immunodeficiency virus type 2 likewise rendered it resistant to both ddGTP and PFA."} {"id": "PMID:1279208", "title": "Transfection-mediated recombination of influenza A virus.", "content": "Several mechanisms, including a high mutation rate and reassortment of genes, have been found to be responsible for the variability of influenza A viruses. RNA recombination would be another mechanism leading to genetic variation; however, recombination has only rarely been reported to occur in influenza viruses. During ribonucleoprotein transfection experiments designed to generate viable influenza viruses from in vitro-synthesized RNA, we discovered several viruses which must have originated from recombination events. The ribonucleoprotein transfection system may enhance the formation of viruses which result from jumping of the viral polymerase between RNAs or from ligation of different viral RNAs. Five different recombinant viruses are described. Two of these, REC1 and REC2, contain a neuraminidase (NA) gene whose defective polyadenylation signal has been repaired via intergenic recombination; 124 and 95 nucleotides have been added, respectively. Another virus, REC5, must have originated by multiple recombination events since it contains a mosaic gene with sequences derived from the NA gene of influenza A/WSN/33 virus and the matrix, polymerase protein PB1, and NA genes of influenza A/PR/8/34 virus.", "contents": "Transfection-mediated recombination of influenza A virus. Several mechanisms, including a high mutation rate and reassortment of genes, have been found to be responsible for the variability of influenza A viruses. RNA recombination would be another mechanism leading to genetic variation; however, recombination has only rarely been reported to occur in influenza viruses. During ribonucleoprotein transfection experiments designed to generate viable influenza viruses from in vitro-synthesized RNA, we discovered several viruses which must have originated from recombination events. The ribonucleoprotein transfection system may enhance the formation of viruses which result from jumping of the viral polymerase between RNAs or from ligation of different viral RNAs. Five different recombinant viruses are described. Two of these, REC1 and REC2, contain a neuraminidase (NA) gene whose defective polyadenylation signal has been repaired via intergenic recombination; 124 and 95 nucleotides have been added, respectively. Another virus, REC5, must have originated by multiple recombination events since it contains a mosaic gene with sequences derived from the NA gene of influenza A/WSN/33 virus and the matrix, polymerase protein PB1, and NA genes of influenza A/PR/8/34 virus."} {"id": "PMID:1279209", "title": "Upstream sequences and cap proximity in the regulation of polyadenylation in ground squirrel hepatitis virus.", "content": "The polyadenylation signal of mammalian hepadnaviruses is unusual in that its hexanucleotide element is the variant UAUAAA rather than AAUAAA. This signal functions inefficiently and must be augmented by multiple activator elements located in the upstream 400 nucleotides (nt) to promote efficient processing. Here we characterize one of these upstream elements, termed PS2, in the ground squirrel hepatitis virus. PS2 is located within the 107 nt 5' to the UAUAAA and raises the efficiency of polyadenylation by this signal from < 10% to 50 to 60%. It can function independently of the more 5' activator elements and conversely is not required for their function. Its action is orientation dependent, and a predicted stem-loop structure within the element is not necessary for its activity. PS2 is the sole upstream element that maps within the terminal redundancy of viral genomic RNA. Thus, it is present, together with the UAUAAA, at both the 5' and 3' ends of this RNA. During genomic RNA synthesis, the poly(A) signals in the 5' repeat are bypassed, while those in the 3' copy are used. The ability of PS2 to function independently of the other, more upstream activators suggests that the absence of the latter elements from the 5' redundancy is insufficient to account for bypass of the 5' poly(A) site, as we had earlier proposed. Rather, the short distance from the cap site to the UAUAAA at the 5' end of genomic RNA actively suppresses its use, as this suppression can be experimentally relieved by increasing this distance to 230 to 400 nt.", "contents": "Upstream sequences and cap proximity in the regulation of polyadenylation in ground squirrel hepatitis virus. The polyadenylation signal of mammalian hepadnaviruses is unusual in that its hexanucleotide element is the variant UAUAAA rather than AAUAAA. This signal functions inefficiently and must be augmented by multiple activator elements located in the upstream 400 nucleotides (nt) to promote efficient processing. Here we characterize one of these upstream elements, termed PS2, in the ground squirrel hepatitis virus. PS2 is located within the 107 nt 5' to the UAUAAA and raises the efficiency of polyadenylation by this signal from < 10% to 50 to 60%. It can function independently of the more 5' activator elements and conversely is not required for their function. Its action is orientation dependent, and a predicted stem-loop structure within the element is not necessary for its activity. PS2 is the sole upstream element that maps within the terminal redundancy of viral genomic RNA. Thus, it is present, together with the UAUAAA, at both the 5' and 3' ends of this RNA. During genomic RNA synthesis, the poly(A) signals in the 5' repeat are bypassed, while those in the 3' copy are used. The ability of PS2 to function independently of the other, more upstream activators suggests that the absence of the latter elements from the 5' redundancy is insufficient to account for bypass of the 5' poly(A) site, as we had earlier proposed. Rather, the short distance from the cap site to the UAUAAA at the 5' end of genomic RNA actively suppresses its use, as this suppression can be experimentally relieved by increasing this distance to 230 to 400 nt."} {"id": "PMID:1279210", "title": "Crystallization of biologically active hemagglutinin-neuraminidase glycoprotein dimers proteolytically cleaved from human parainfluenza virus type 1.", "content": "We isolated, purified, and characterized the hemagglutinin-neuraminidase (HN) of human parainfluenza virus type 1, with the ultimate goal of producing crystals suitable for three-dimensional X-ray structure analysis. Pronase was used to cleave the globular head of the HN molecule directly from virus particles, forming HN monomers and dimers. The purified dimers retained neuraminidase and hemadsorption activity and were recognized by 14 anti-HN monoclonal antibodies, demonstrating intact HN antigenic structure and function. N-terminal sequence analysis of the dimers showed that cleavage had occurred at amino acid 136 or 137, freeing the C-terminal 438 or 439 amino acids. On electron micrography, the dimer appeared as two box-shaped structures, each approximately 5 by 5 nm. When the purified HN dimers were crystallized in hanging drops by vapor diffusion against 20% polyethylene glycol 3350, they formed both rectangular plates and needlelike crystals. The rectangular crystals diffracted X-rays, indicating an ordered atomic structure. However, the resolution was approximately 10 A (1 nm), insufficient for three-dimensional structural analysis. Experiments to improve the resolution by increasing the size and quality of the crystals are in progress.", "contents": "Crystallization of biologically active hemagglutinin-neuraminidase glycoprotein dimers proteolytically cleaved from human parainfluenza virus type 1. We isolated, purified, and characterized the hemagglutinin-neuraminidase (HN) of human parainfluenza virus type 1, with the ultimate goal of producing crystals suitable for three-dimensional X-ray structure analysis. Pronase was used to cleave the globular head of the HN molecule directly from virus particles, forming HN monomers and dimers. The purified dimers retained neuraminidase and hemadsorption activity and were recognized by 14 anti-HN monoclonal antibodies, demonstrating intact HN antigenic structure and function. N-terminal sequence analysis of the dimers showed that cleavage had occurred at amino acid 136 or 137, freeing the C-terminal 438 or 439 amino acids. On electron micrography, the dimer appeared as two box-shaped structures, each approximately 5 by 5 nm. When the purified HN dimers were crystallized in hanging drops by vapor diffusion against 20% polyethylene glycol 3350, they formed both rectangular plates and needlelike crystals. The rectangular crystals diffracted X-rays, indicating an ordered atomic structure. However, the resolution was approximately 10 A (1 nm), insufficient for three-dimensional structural analysis. Experiments to improve the resolution by increasing the size and quality of the crystals are in progress."} {"id": "PMID:1279211", "title": "Pilot study to evaluate impact of a policy of adjuvant chemotherapy for high risk stage 1 malignant teratoma on overall relapse rate of stage 1 cancer patients.", "content": "A total of 41 patients with stage 1 malignant teratoma of the testis treated from January 1986 to June 1990 was entered into a pilot study of 2 courses of adjuvant cisplatin-based combination chemotherapy. Of the patients 22 had a high or intermediate risk of relapse according to the Medical Research Council (United Kingdom) prognostic factor analysis and surveillance was instituted for 19 patients with a low relapse risk. The overall relapse rate in this group of patients (median followup 2 years) was 9.7% (5% in the adjuvant group and 16% in the surveillance group), which was significantly better than the 35% rate in the historical series treated by surveillance from 1980 to 1985 and equaled or was possibly better than that reported from adjuvant retroperitoneal lymph node dissection. Justification for consideration of 1 course of adjuvant treatment for such cases is reviewed, and the need for examination of such an approach in a neoadjuvant setting with either lymph node dissection or surveillance is examined.", "contents": "Pilot study to evaluate impact of a policy of adjuvant chemotherapy for high risk stage 1 malignant teratoma on overall relapse rate of stage 1 cancer patients. A total of 41 patients with stage 1 malignant teratoma of the testis treated from January 1986 to June 1990 was entered into a pilot study of 2 courses of adjuvant cisplatin-based combination chemotherapy. Of the patients 22 had a high or intermediate risk of relapse according to the Medical Research Council (United Kingdom) prognostic factor analysis and surveillance was instituted for 19 patients with a low relapse risk. The overall relapse rate in this group of patients (median followup 2 years) was 9.7% (5% in the adjuvant group and 16% in the surveillance group), which was significantly better than the 35% rate in the historical series treated by surveillance from 1980 to 1985 and equaled or was possibly better than that reported from adjuvant retroperitoneal lymph node dissection. Justification for consideration of 1 course of adjuvant treatment for such cases is reviewed, and the need for examination of such an approach in a neoadjuvant setting with either lymph node dissection or surveillance is examined."} {"id": "PMID:1279212", "title": "Quantitative measurements of prostatic blood flow and blood volume by positron emission tomography.", "content": "Prostatic blood flow was measured with 15oxygen-water by positron emission tomography using a 1-compartment model. A dynamic study method was applied to 9 normal subjects, 6 with benign prostatic hypertrophy (BPH) and 11 with advanced stages C to D2 prostatic adenocarcinoma. Prostatic blood flow was 15.7 +/- 7.5 ml. per minute per 100 gm. in normal controls, 17.7 +/- 5.2 ml. per minute per 100 gm. in BPH patients and 29.4 +/- 7.8 ml. per minute per 100 gm. in prostatic cancer patients. Prostatic blood flow negatively correlated well with age in the normal subjects. Prostatic blood volume was also estimated by the steady state method using 15oxygen-carbon monoxide. Prostatic blood volume was 8.1 +/- 2.6% in normal controls, 8.9 +/- 1.1% in BPH patients and 6.1 +/- 2.1% in prostatic cancer patients. Blood flow in the prostatic cancer tissue was higher than that in the normal (p < 0.001) or BPH (p < 0.01) tissue. A significant difference in prostatic blood volume was also observed between BPH and cancer tissues (p < 0.02).", "contents": "Quantitative measurements of prostatic blood flow and blood volume by positron emission tomography. Prostatic blood flow was measured with 15oxygen-water by positron emission tomography using a 1-compartment model. A dynamic study method was applied to 9 normal subjects, 6 with benign prostatic hypertrophy (BPH) and 11 with advanced stages C to D2 prostatic adenocarcinoma. Prostatic blood flow was 15.7 +/- 7.5 ml. per minute per 100 gm. in normal controls, 17.7 +/- 5.2 ml. per minute per 100 gm. in BPH patients and 29.4 +/- 7.8 ml. per minute per 100 gm. in prostatic cancer patients. Prostatic blood flow negatively correlated well with age in the normal subjects. Prostatic blood volume was also estimated by the steady state method using 15oxygen-carbon monoxide. Prostatic blood volume was 8.1 +/- 2.6% in normal controls, 8.9 +/- 1.1% in BPH patients and 6.1 +/- 2.1% in prostatic cancer patients. Blood flow in the prostatic cancer tissue was higher than that in the normal (p < 0.001) or BPH (p < 0.01) tissue. A significant difference in prostatic blood volume was also observed between BPH and cancer tissues (p < 0.02)."} {"id": "PMID:1279213", "title": "The characterization of nonbacterial prostatitis: search for an etiology.", "content": "Nonbacterial prostatitis is often difficult to differentiate from other prostatic complaints and remains a vaguely characterized syndrome. Prostatic fluid inflammatory cells and elevated immunoglobulins raise the suspicion that this syndrome is caused by some undetected infection. Prostatic fluid antibodies against Chlamydia trachomatis, Ureaplasma urealyticum, staphylococcus, Staphylococcus faecalis, Bacteroides fragilis and Clostridium perfringens were measured in men with nonbacterial and bacterial prostatitis, and men without urinary symptoms by an enzyme-linked immunosorbent assay. Prostate specific antigen and prostatic acid phosphatase were measured in the prostatic fluid as indirect measures of secretory activity. Of 44 men with nonbacterial prostatitis 9 (20%) had detectable prostatic fluid antichlamydial antibody titers, compared with 3 of 25 control men (12%) and 2 of 13 (15%) with bacterial prostatitis--no evidence for a higher prevalence of prostatic fluid antichlamydial antibody in men with nonbacterial prostatitis. Prostatic antibodies to the other organisms were rarely detected. When compared with unaffected men the low levels of prostate specific antigen and prostatic acid phosphatase, and more alkaline prostatic fluid in men with bacterial and nonbacterial prostatitis suggest that secretory dysfunction accompanies the inflammation. These data show that none of the organisms studied caused the majority of the cases of nonbacterial prostatitis and that either an agent as yet unidentified or multiple agents may be involved in the etiology of nonbacterial prostatitis.", "contents": "The characterization of nonbacterial prostatitis: search for an etiology. Nonbacterial prostatitis is often difficult to differentiate from other prostatic complaints and remains a vaguely characterized syndrome. Prostatic fluid inflammatory cells and elevated immunoglobulins raise the suspicion that this syndrome is caused by some undetected infection. Prostatic fluid antibodies against Chlamydia trachomatis, Ureaplasma urealyticum, staphylococcus, Staphylococcus faecalis, Bacteroides fragilis and Clostridium perfringens were measured in men with nonbacterial and bacterial prostatitis, and men without urinary symptoms by an enzyme-linked immunosorbent assay. Prostate specific antigen and prostatic acid phosphatase were measured in the prostatic fluid as indirect measures of secretory activity. Of 44 men with nonbacterial prostatitis 9 (20%) had detectable prostatic fluid antichlamydial antibody titers, compared with 3 of 25 control men (12%) and 2 of 13 (15%) with bacterial prostatitis--no evidence for a higher prevalence of prostatic fluid antichlamydial antibody in men with nonbacterial prostatitis. Prostatic antibodies to the other organisms were rarely detected. When compared with unaffected men the low levels of prostate specific antigen and prostatic acid phosphatase, and more alkaline prostatic fluid in men with bacterial and nonbacterial prostatitis suggest that secretory dysfunction accompanies the inflammation. These data show that none of the organisms studied caused the majority of the cases of nonbacterial prostatitis and that either an agent as yet unidentified or multiple agents may be involved in the etiology of nonbacterial prostatitis."} {"id": "PMID:1279214", "title": "A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia.", "content": "The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy.", "contents": "A randomized, placebo-controlled multicenter study of the efficacy and safety of terazosin in the treatment of benign prostatic hyperplasia. The clinical manifestations of benign prostatic hyperplasia (BPH) are related primarily to bladder outlet obstruction resulting from enlargement of the prostate gland. Transurethral prostatectomy is the most common treatment currently offered for BPH in the United States. The primary objective of the present randomized placebo controlled multicenter study was to determine the efficacy and safety of terazosin, a selective long-acting alpha 1-blocker, for the treatment of symptomatic BPH. A total of 285 men with symptomatic BPH was randomly assigned in equal proportions to receive placebo, or 2, 5 or 10 mg. terazosin administered once daily. Of the patients 237 completed the 4-week single-blind placebo lead-in and 12-week double-blind treatment periods. The primary outcome parameters were changes in peak and mean urinary flow rates, and changes in the Boyarsky symptom scores. All terazosin treatment groups exhibited significantly greater decreases in total Boyarsky symptom score than the placebo group. The 10 mg. terazosin group exhibited significantly greater increases in peak and mean urinary flow rates than the placebo group. The improvements in symptom scores and urinary flow rates did not reach a plateau within the dose range evaluated, suggesting that further efficacy may be achieved with doses of terazosin exceeding 10 mg. This study unequivocally demonstrates the safety and efficacy of terazosin for the treatment of BPH. Selective alpha 1-blockade is likely to gain widespread acceptance for the treatment of BPH due to its safety and efficacy."} {"id": "PMID:1279216", "title": "Recurrent prostate cancer despite undetectable prostate specific antigen.", "content": "Serum prostate specific antigen (PSA) is a sensitive tumor marker following definitive therapy for adenocarcinoma of the prostate. Detectable levels of PSA after radical prostatectomy indicate residual and/or recurrent cancer. Therefore, we were surprised to document recurrent cancer following radical retropubic prostatectomy in a man who had undetectable serum PSA levels. This observation suggests that careful clinical monitoring remains essential after definitive therapy, since rare patients may have recurrent and/or residual carcinoma despite undetectable levels of PSA.", "contents": "Recurrent prostate cancer despite undetectable prostate specific antigen. Serum prostate specific antigen (PSA) is a sensitive tumor marker following definitive therapy for adenocarcinoma of the prostate. Detectable levels of PSA after radical prostatectomy indicate residual and/or recurrent cancer. Therefore, we were surprised to document recurrent cancer following radical retropubic prostatectomy in a man who had undetectable serum PSA levels. This observation suggests that careful clinical monitoring remains essential after definitive therapy, since rare patients may have recurrent and/or residual carcinoma despite undetectable levels of PSA."} {"id": "PMID:1279217", "title": "Hard measures of subjective outcomes: validating symptom indexes in urology.", "content": "Scientifically validated (accurate), and reproducible (precise) methods of assessing the frequency and severity of patient symptoms are becoming more widely used in medicine. Such a symptom index has been developed for patients with benign prostatic hyperplasia, and may find use in clinical practice and research. The criteria for developing and validating such indexes are presented, using the new benign prostatic hyperplasia symptom index as an example. The same approach can be applied to many other disease entities in urology that demand a quantitation of the illness experience from the perspective of the patients.", "contents": "Hard measures of subjective outcomes: validating symptom indexes in urology. Scientifically validated (accurate), and reproducible (precise) methods of assessing the frequency and severity of patient symptoms are becoming more widely used in medicine. Such a symptom index has been developed for patients with benign prostatic hyperplasia, and may find use in clinical practice and research. The criteria for developing and validating such indexes are presented, using the new benign prostatic hyperplasia symptom index as an example. The same approach can be applied to many other disease entities in urology that demand a quantitation of the illness experience from the perspective of the patients."} {"id": "PMID:1279218", "title": "The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association.", "content": "A symptom index for benign prostatic hyperplasia (BPH) was developed and validated by a multidisciplinary measurement committee of the American Urological Association (AUA). Validation studies were conducted involving a total of 210 BPH patients and 108 control subjects. The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's alpha = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p < 0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols.", "contents": "The American Urological Association symptom index for benign prostatic hyperplasia. The Measurement Committee of the American Urological Association. A symptom index for benign prostatic hyperplasia (BPH) was developed and validated by a multidisciplinary measurement committee of the American Urological Association (AUA). Validation studies were conducted involving a total of 210 BPH patients and 108 control subjects. The final AUA symptom index includes 7 questions covering frequency, nocturia, weak urinary stream, hesitancy, intermittence, incomplete emptying and urgency. On revalidation, the index was internally consistent (Cronbach's alpha = 0.86) and the score generated had excellent test-retest reliability (r = 0.92). Scores were highly correlated with subjects' global ratings of the magnitude of their urinary problem (r = 0.65 to 0.72) and powerfully discriminated between BPH and control subjects (receiver operating characteristic area 0.85). Finally, the index was sensitive to change, with preoperative scores decreasing from a mean of 17.6 to 7.1 by 4 weeks after prostatectomy (p < 0.001). The AUA symptom index is clinically sensible, reliable, valid and responsive. It is practical for use in practice and for inclusion in research protocols."} {"id": "PMID:1279219", "title": "Correlation of the American Urological Association symptom index with self-administered versions of the Madsen-Iversen, Boyarsky and Maine Medical Assessment Program symptom indexes. Measurement Committee of the American Urological Association.", "content": "We correlated the American Urological Association (AUA) symptom index with other indexes that have been used to measure symptoms for benign prostatic hyperplasia (BPH) and compared their psychometric properties. A self-administered questionnaire that allowed derivation of AUA, Maine Medical Assessment Program, Madsen-Iversen and Boyarsky symptom scores was completed by 76 men with clinically defined BPH, 59 younger control subjects, and 27 men before and after prostatectomy. The scores from the 4 indexes were strongly correlated (r = 0.77 to 0.93). All 4 indexes had good internal consistency and test-retest reliabilities. All indexes were predictive of patient global ratings of the degree of bother from the urinary condition. The AUA index discriminated BPH patients from controls significantly better than the Maine Medical Assessment Program index, and equivalently to the Madsen-Iversen and Boyarsky indexes (despite having fewer items). All 4 indexes were responsive when BPH patients underwent prostatectomy, although the AUA and Madsen-Iversen indexes were significantly more sensitive.", "contents": "Correlation of the American Urological Association symptom index with self-administered versions of the Madsen-Iversen, Boyarsky and Maine Medical Assessment Program symptom indexes. Measurement Committee of the American Urological Association. We correlated the American Urological Association (AUA) symptom index with other indexes that have been used to measure symptoms for benign prostatic hyperplasia (BPH) and compared their psychometric properties. A self-administered questionnaire that allowed derivation of AUA, Maine Medical Assessment Program, Madsen-Iversen and Boyarsky symptom scores was completed by 76 men with clinically defined BPH, 59 younger control subjects, and 27 men before and after prostatectomy. The scores from the 4 indexes were strongly correlated (r = 0.77 to 0.93). All 4 indexes had good internal consistency and test-retest reliabilities. All indexes were predictive of patient global ratings of the degree of bother from the urinary condition. The AUA index discriminated BPH patients from controls significantly better than the Maine Medical Assessment Program index, and equivalently to the Madsen-Iversen and Boyarsky indexes (despite having fewer items). All 4 indexes were responsive when BPH patients underwent prostatectomy, although the AUA and Madsen-Iversen indexes were significantly more sensitive."} {"id": "PMID:1279221", "title": "Establishment and characterization of a human primary prostatic adenocarcinoma cell line (ND-1).", "content": "A human primary prostatic adenocarcinoma cell line named ND-1 has been established in long term tissue culture. The cultured cells show growth in both monolayers and in soft agar suspension and produce subcutaneous tumors in nude mice. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with a modal chromosome number of 62, and multiple marker chromosomes with 25-30% structural abnormalities. Ploidy analysis revealed that the majority of ND-1 cells (67%) had a DNA mass of 10.1 picogram and DNA index of 1.41. Nineteen percent of cells had a DNA mass of 21.3 picogram and DNA index of 3.0. Electron microscopic studies revealed common features of neoplastic epithelial cells such as numerous microvilli, junctional complexes, abnormal nuclei, nucleoli, and mitochondria. Due to the absence of a structurally normal Y chromosome, confirmation of the presence of a derived Y chromosome was achieved through the use of C-banding and through fluorescent in situ hybridization with a Y chromosome repeat probe. Tandem E PSA immunoenzymatic assay revealed that these ND-1 cells secrete small amounts of prostate specific antigen.", "contents": "Establishment and characterization of a human primary prostatic adenocarcinoma cell line (ND-1). A human primary prostatic adenocarcinoma cell line named ND-1 has been established in long term tissue culture. The cultured cells show growth in both monolayers and in soft agar suspension and produce subcutaneous tumors in nude mice. Cytogenetic analysis by G-banding demonstrated an aneuploid karyotype with a modal chromosome number of 62, and multiple marker chromosomes with 25-30% structural abnormalities. Ploidy analysis revealed that the majority of ND-1 cells (67%) had a DNA mass of 10.1 picogram and DNA index of 1.41. Nineteen percent of cells had a DNA mass of 21.3 picogram and DNA index of 3.0. Electron microscopic studies revealed common features of neoplastic epithelial cells such as numerous microvilli, junctional complexes, abnormal nuclei, nucleoli, and mitochondria. Due to the absence of a structurally normal Y chromosome, confirmation of the presence of a derived Y chromosome was achieved through the use of C-banding and through fluorescent in situ hybridization with a Y chromosome repeat probe. Tandem E PSA immunoenzymatic assay revealed that these ND-1 cells secrete small amounts of prostate specific antigen."} {"id": "PMID:1279222", "title": "In vitro studies on the effect of cofactors on the 5 alpha-reductase and 3 alpha- and 3 beta-hydroxysteroid reductase activities in the hyperplastic human prostate.", "content": "Many studies have intimated that the accumulation and hence elevation of dihydrotestosterone (DHT) in the human prostate may be the primary factor in the development of benign prostatic hyperplasia (BPH). This accumulation has been explained in terms of an increase in the 5 alpha-reductase enzymatic activity which converts testosterone to DHT and a decrease in the relative activities of the 3 alpha-HSORred and 3 beta-HSORred enzymes. To investigate this hypothesis further, the activities of these two enzymes were studied in the presence and absence of NADPH in benign hyperplastic tissue and in normal peripheral (NPR) and benign hyperplastic periurethral (BPH) tissue taken from the same prostate. The results of these studies demonstrate a several fold increase in the activities of 3 alpha-HSORred and 3 beta-HSORred in the presence of NADPH in the hyperplastic human prostate. This increase in the activities of these two enzymes is found to the same degree in normal peripheral and benign hyperplastic periurethral tissue taken from the same prostate. There was no difference in percent increase in 3 alpha- and 3 beta-diol formation from DHT with NADPH in normal peripheral versus benign hyperplastic periurethral prostatic tissue. In subsequent experiments, Vmax/Km, as an index of the enzymatic capacity of the 3 alpha-HSORred and 3 beta-HSORred enzymes, was determined in both NPR and BPH tissue in media fortified with one mM NADPH. This quotient was found to be essentially the same in NPR and BPH tissue for both the 3 alpha-HSORred and the 3 beta-HSORred. Subsequently, the Vmax/Km value for the 5 alpha-reductase in BPH tissue was found to be equal to the combined Vmax/Km values of the 3 alpha-HSORred and 3 beta-HSORred. The reverse reaction or the conversion of 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol is completely blocked in a medium containing one mM NADPH. These studies suggest that the concentration of DHT in prostatic tissue is dependent on the level of NADPH necessary for the 3 alpha-HSORred and 3 beta-HSORred enzymes to convert DHT to its respective diols.", "contents": "In vitro studies on the effect of cofactors on the 5 alpha-reductase and 3 alpha- and 3 beta-hydroxysteroid reductase activities in the hyperplastic human prostate. Many studies have intimated that the accumulation and hence elevation of dihydrotestosterone (DHT) in the human prostate may be the primary factor in the development of benign prostatic hyperplasia (BPH). This accumulation has been explained in terms of an increase in the 5 alpha-reductase enzymatic activity which converts testosterone to DHT and a decrease in the relative activities of the 3 alpha-HSORred and 3 beta-HSORred enzymes. To investigate this hypothesis further, the activities of these two enzymes were studied in the presence and absence of NADPH in benign hyperplastic tissue and in normal peripheral (NPR) and benign hyperplastic periurethral (BPH) tissue taken from the same prostate. The results of these studies demonstrate a several fold increase in the activities of 3 alpha-HSORred and 3 beta-HSORred in the presence of NADPH in the hyperplastic human prostate. This increase in the activities of these two enzymes is found to the same degree in normal peripheral and benign hyperplastic periurethral tissue taken from the same prostate. There was no difference in percent increase in 3 alpha- and 3 beta-diol formation from DHT with NADPH in normal peripheral versus benign hyperplastic periurethral prostatic tissue. In subsequent experiments, Vmax/Km, as an index of the enzymatic capacity of the 3 alpha-HSORred and 3 beta-HSORred enzymes, was determined in both NPR and BPH tissue in media fortified with one mM NADPH. This quotient was found to be essentially the same in NPR and BPH tissue for both the 3 alpha-HSORred and the 3 beta-HSORred. Subsequently, the Vmax/Km value for the 5 alpha-reductase in BPH tissue was found to be equal to the combined Vmax/Km values of the 3 alpha-HSORred and 3 beta-HSORred. The reverse reaction or the conversion of 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol is completely blocked in a medium containing one mM NADPH. These studies suggest that the concentration of DHT in prostatic tissue is dependent on the level of NADPH necessary for the 3 alpha-HSORred and 3 beta-HSORred enzymes to convert DHT to its respective diols."} {"id": "PMID:1279223", "title": "Epidemiology of bladder emptying symptoms in elderly men.", "content": "We provide estimates of the prevalence, incidence and remission of difficult bladder emptying symptoms (prostatism) among noninstitutionalized men 60 years old and older living in a community in the United States. The prevalence of 1 or more symptoms of prostatism (hesitancy, straining, weak stream, intermittency or use of a catheter) among men who never had prostatic surgery is 35%. The annual incidence rates during years 1 and 2 of followup were 16.4% and 16.1%, respectively. Remission of symptoms of prostatism also was observed. Of the respondents with severe symptoms at baseline 22.9% were asymptomatic 1 year later. The prevalence of prostatic surgery in this population was 20%. The annual incidence rates during years 1 and 2 of followup were 2.6% and 3.3%, respectively. Urological and nonurological correlates of prostatism are identified. The irritative bladder symptoms are all significantly associated with moderate to severe bladder emptying symptoms (p < 0.0005). Nonurological conditions that also are associated with moderate to severe symptoms of prostatism include use of sedatives or tranquilizers, arthritis, poor health status and transient ischemic attacks. These observations are the initial step in documenting and understanding the various symptoms of prostatism, and its application in clinical practice.", "contents": "Epidemiology of bladder emptying symptoms in elderly men. We provide estimates of the prevalence, incidence and remission of difficult bladder emptying symptoms (prostatism) among noninstitutionalized men 60 years old and older living in a community in the United States. The prevalence of 1 or more symptoms of prostatism (hesitancy, straining, weak stream, intermittency or use of a catheter) among men who never had prostatic surgery is 35%. The annual incidence rates during years 1 and 2 of followup were 16.4% and 16.1%, respectively. Remission of symptoms of prostatism also was observed. Of the respondents with severe symptoms at baseline 22.9% were asymptomatic 1 year later. The prevalence of prostatic surgery in this population was 20%. The annual incidence rates during years 1 and 2 of followup were 2.6% and 3.3%, respectively. Urological and nonurological correlates of prostatism are identified. The irritative bladder symptoms are all significantly associated with moderate to severe bladder emptying symptoms (p < 0.0005). Nonurological conditions that also are associated with moderate to severe symptoms of prostatism include use of sedatives or tranquilizers, arthritis, poor health status and transient ischemic attacks. These observations are the initial step in documenting and understanding the various symptoms of prostatism, and its application in clinical practice."} {"id": "PMID:1279224", "title": "Detection of human papillomavirus in the prostate by polymerase chain reaction and in situ hybridization.", "content": "Human papillomavirus is associated with a variety of anogenital lesions, including genital warts, precancers and cancers. In male patients human papillomavirus has been identified in proliferative lesions ranging from penile and urethral warts to penile and prostatic cancers. We examined the association of human papillomavirus deoxyribonucleic acid (DNA) in 84 prostate tissue specimens. Specimens were selected from radical prostatectomy, transurethral resection or transrectal biopsy procedures. A total of 60 formalin-fixed, paraffin-embedded tissues (24 prostate cancer specimens, 16 benign prostatic hyperplasia specimens and 20 normal specimens) was examined by polymerase chain reaction and in situ hybridization. Also, 24 gelatin-embedded frozen prostate cancer specimens were examined for human papillomavirus DNA by polymerase chain reaction. Of the specimens 69 were deemed adequate for polymerase chain reaction analysis, whereas all 60 paraffin-embedded tissues were sufficient for in situ hybridization. Human papillomavirus DNA was detected in 2 normal tissues and 6 prostate cancers using polymerase chain reaction. None of the benign prostatic hyperplasia specimens was positive for human papillomavirus. Human papillomavirus typing results indicated that virus type 16 was present in each of the 8 positive specimens. Confirmation of the presence of human papillomavirus was obtained for 1 of the prostate cancers by nonisotopic in situ hybridization with biotinylated human papillomavirus genomic probes. The low prevalence of human papillomavirus in this study population does not strongly support an etiological role for the virus in prostate cancer.", "contents": "Detection of human papillomavirus in the prostate by polymerase chain reaction and in situ hybridization. Human papillomavirus is associated with a variety of anogenital lesions, including genital warts, precancers and cancers. In male patients human papillomavirus has been identified in proliferative lesions ranging from penile and urethral warts to penile and prostatic cancers. We examined the association of human papillomavirus deoxyribonucleic acid (DNA) in 84 prostate tissue specimens. Specimens were selected from radical prostatectomy, transurethral resection or transrectal biopsy procedures. A total of 60 formalin-fixed, paraffin-embedded tissues (24 prostate cancer specimens, 16 benign prostatic hyperplasia specimens and 20 normal specimens) was examined by polymerase chain reaction and in situ hybridization. Also, 24 gelatin-embedded frozen prostate cancer specimens were examined for human papillomavirus DNA by polymerase chain reaction. Of the specimens 69 were deemed adequate for polymerase chain reaction analysis, whereas all 60 paraffin-embedded tissues were sufficient for in situ hybridization. Human papillomavirus DNA was detected in 2 normal tissues and 6 prostate cancers using polymerase chain reaction. None of the benign prostatic hyperplasia specimens was positive for human papillomavirus. Human papillomavirus typing results indicated that virus type 16 was present in each of the 8 positive specimens. Confirmation of the presence of human papillomavirus was obtained for 1 of the prostate cancers by nonisotopic in situ hybridization with biotinylated human papillomavirus genomic probes. The low prevalence of human papillomavirus in this study population does not strongly support an etiological role for the virus in prostate cancer."} {"id": "PMID:1279225", "title": "Diagnostic methods in the detection of prostate cancer: a study of a randomly selected population of 2,400 men.", "content": "We investigated the value of digital rectal examination, transrectal ultrasonography and prostatic specific antigen (PSA) analysis as aids in general clinical practice and in the early detection of prostate cancer. Of a randomly selected population of 2,400 men 55 to 70 years old who were offered examination with digital rectal examination, transrectal ultrasound and PSA analysis, 1,782 (74%) accepted and prostate cancer was detected in 65 (3.6%). When the transrectal ultrasound results were also considered the detection rate of digital rectal examination (2.3%) was increased by 50% and the number of stage T2A or less tumors was doubled. At reexamination due to markedly high PSA values (7 micrograms/l. or more) only a few additional cancers (5%) were detected. However, it is noteworthy that 80% of the detected cancers were found among the subgroup with abnormal PSA values (4 micrograms/l. or more) and comprising 17% of the study population, which suggests the possibility of selecting a risk group at mass screening. Moreover, the positive predictive value increased from 4% (when only digital rectal examination was positive) to 71% for the combination of positive digital rectal examination, positive transrectal ultrasound and an increased PSA concentration (that is 7 micrograms/l. or greater).", "contents": "Diagnostic methods in the detection of prostate cancer: a study of a randomly selected population of 2,400 men. We investigated the value of digital rectal examination, transrectal ultrasonography and prostatic specific antigen (PSA) analysis as aids in general clinical practice and in the early detection of prostate cancer. Of a randomly selected population of 2,400 men 55 to 70 years old who were offered examination with digital rectal examination, transrectal ultrasound and PSA analysis, 1,782 (74%) accepted and prostate cancer was detected in 65 (3.6%). When the transrectal ultrasound results were also considered the detection rate of digital rectal examination (2.3%) was increased by 50% and the number of stage T2A or less tumors was doubled. At reexamination due to markedly high PSA values (7 micrograms/l. or more) only a few additional cancers (5%) were detected. However, it is noteworthy that 80% of the detected cancers were found among the subgroup with abnormal PSA values (4 micrograms/l. or more) and comprising 17% of the study population, which suggests the possibility of selecting a risk group at mass screening. Moreover, the positive predictive value increased from 4% (when only digital rectal examination was positive) to 71% for the combination of positive digital rectal examination, positive transrectal ultrasound and an increased PSA concentration (that is 7 micrograms/l. or greater)."} {"id": "PMID:1279226", "title": "The value of serum enzymatic acid phosphatase in the staging of localized prostate cancer.", "content": "With the development of reliable assays for the measurement of prostate specific antigen (PSA), the use of serum enzymatic acid phosphatase in the staging of disease before radical prostatectomy has been called into question. We evaluated 460 consecutive men who were referred to our institution as candidates for radical prostatectomy. Staging evaluation included digital rectal examination, serum measurements of enzymatic acid phosphatase and PSA, bone scans and, in patients in whom advanced clinical stage was anticipated, computerized tomography, magnetic resonance imaging or transrectal ultrasonography. Of the 460 men 21 (4.6%) had elevations of serum enzymatic acid phosphatase. All 19 men with elevations who were fully evaluated proved to have either positive bone scans, extraprostatic extension of disease, PSA greater than 100 ng./ml., positive lymph nodes or positive seminal vesicles. However, in 17 of the 21 men (81%) with elevated serum enzymatic acid phosphatase advanced disease was detected by either abnormal digital rectal examination or PSA alone. Thus, serum enzymatic acid phosphatase provided unique information in only 4 of the entire study population (0.9%). Recognizing this low yield of unique information, we believe that measurements of serum enzymatic acid phosphatase are no longer mandatory before radical prostatectomy but may provide important confirmatory information in patients in whom advanced disease is suspected.", "contents": "The value of serum enzymatic acid phosphatase in the staging of localized prostate cancer. With the development of reliable assays for the measurement of prostate specific antigen (PSA), the use of serum enzymatic acid phosphatase in the staging of disease before radical prostatectomy has been called into question. We evaluated 460 consecutive men who were referred to our institution as candidates for radical prostatectomy. Staging evaluation included digital rectal examination, serum measurements of enzymatic acid phosphatase and PSA, bone scans and, in patients in whom advanced clinical stage was anticipated, computerized tomography, magnetic resonance imaging or transrectal ultrasonography. Of the 460 men 21 (4.6%) had elevations of serum enzymatic acid phosphatase. All 19 men with elevations who were fully evaluated proved to have either positive bone scans, extraprostatic extension of disease, PSA greater than 100 ng./ml., positive lymph nodes or positive seminal vesicles. However, in 17 of the 21 men (81%) with elevated serum enzymatic acid phosphatase advanced disease was detected by either abnormal digital rectal examination or PSA alone. Thus, serum enzymatic acid phosphatase provided unique information in only 4 of the entire study population (0.9%). Recognizing this low yield of unique information, we believe that measurements of serum enzymatic acid phosphatase are no longer mandatory before radical prostatectomy but may provide important confirmatory information in patients in whom advanced disease is suspected."} {"id": "PMID:1279232", "title": "[The clinical effect of intravenous regional sympathectomy with guanethidine in the management of sympathetically maintained pain].", "content": "We treated 25 patients suffering from sympathetically maintained pain with intravenous regional sympathectomy with guanethidine. Of these patients, 18 had reflex sympathetic dystrophy; 5 had causalgia; and 2 had shoulder hand syndrome. The visual analog scale before IRS therapy was 6.1 +/- 0.3, and after therapy, it was 2.3 +/- 0.4. The mean rate of improvement was 54.2% in reflex sympathetic dystrophy and 81.0% in causalgia. The therapy was particularly effective in patients with shoulder hand syndrome. These results suggest that intravenous regional sympathectomy with guanethidine could be effective for sympathetically maintained pain.", "contents": "[The clinical effect of intravenous regional sympathectomy with guanethidine in the management of sympathetically maintained pain]. We treated 25 patients suffering from sympathetically maintained pain with intravenous regional sympathectomy with guanethidine. Of these patients, 18 had reflex sympathetic dystrophy; 5 had causalgia; and 2 had shoulder hand syndrome. The visual analog scale before IRS therapy was 6.1 +/- 0.3, and after therapy, it was 2.3 +/- 0.4. The mean rate of improvement was 54.2% in reflex sympathetic dystrophy and 81.0% in causalgia. The therapy was particularly effective in patients with shoulder hand syndrome. These results suggest that intravenous regional sympathectomy with guanethidine could be effective for sympathetically maintained pain."} {"id": "PMID:1279233", "title": "[Detection and identification of pathogenic bacteria by polymerase chain reaction with primers from DNA sequence of ribosomal RNA].", "content": "Applicability of the polymerase chain reaction method for identification of pathogenic bacteria was examined with the primers synthesized from the ribosomal RNA gene sequence containing both homologous and species-specific regions of bacterial species from Mycoplasma to Mycobacteria. Two out of the nine sets of promoters prepared, each covering about 650 nucleotides spanning from 16S RNA to 23S RNA regions, produced the corresponding DNA fragments from all the strains tested, and another set did so from all species but Mycoplasma. This method enabled one to detect and identify E. coli in a sample containing 2 x 10(2) CFU. The restriction enzyme patterns of the PCR products obtained with Hae-III, Hha-I, Mbo-I, Msp-I, Rsa-I and Taq-I were so characteristic as to differentiate one species from another. Ten strains of E. coli showed identical restriction patterns and 10 of S. aureus also showed identical patterns indicating that the restriction pattern is species-specific. The method may be applicable to detection and identification of a certain species bacteria which are suspected to be consealed in water or food samples, or clinical specimens, especially when the consealed bacterial genus or species can not be predicted.", "contents": "[Detection and identification of pathogenic bacteria by polymerase chain reaction with primers from DNA sequence of ribosomal RNA]. Applicability of the polymerase chain reaction method for identification of pathogenic bacteria was examined with the primers synthesized from the ribosomal RNA gene sequence containing both homologous and species-specific regions of bacterial species from Mycoplasma to Mycobacteria. Two out of the nine sets of promoters prepared, each covering about 650 nucleotides spanning from 16S RNA to 23S RNA regions, produced the corresponding DNA fragments from all the strains tested, and another set did so from all species but Mycoplasma. This method enabled one to detect and identify E. coli in a sample containing 2 x 10(2) CFU. The restriction enzyme patterns of the PCR products obtained with Hae-III, Hha-I, Mbo-I, Msp-I, Rsa-I and Taq-I were so characteristic as to differentiate one species from another. Ten strains of E. coli showed identical restriction patterns and 10 of S. aureus also showed identical patterns indicating that the restriction pattern is species-specific. The method may be applicable to detection and identification of a certain species bacteria which are suspected to be consealed in water or food samples, or clinical specimens, especially when the consealed bacterial genus or species can not be predicted."} {"id": "PMID:1279234", "title": "[Frequency of the development of RNA-rich reticulocytes in allogeneic bone marrow transplant recipients].", "content": "We measured appearance rates of RNA-rich reticulocytes in 8 patients undergoing allogeneic bone marrow transplantation, using a Sysmex R-1000 reticulocyte counter which utilizes laser flow cytometry. The changes in proportion of RNA-rich reticulocytes (high fluorescence ratio: HFR) and maturation index (MI: HFR + middle fluorescence ratio/low fluorescence ratio) were compared with those of WBC, neutrophil or reticulocyte counts. Engraftment was defined as an HFR of greater than or equal to 5% or a MI of greater than or equal to 15%. Engraftment was confirmed significantly earlier by HFR (13.5 +/- 2.4 days) and MI (13.1 +/- 2.9 days) than by neutrophils (17.1 +/- 3.2 days) or reticulocytes (20.4 +/- 6.2 days). The maturation of reticulocytes would be a useful indicator for engraftment or recovery from marrow aplasia in cases of bone marrow transplantation.", "contents": "[Frequency of the development of RNA-rich reticulocytes in allogeneic bone marrow transplant recipients]. We measured appearance rates of RNA-rich reticulocytes in 8 patients undergoing allogeneic bone marrow transplantation, using a Sysmex R-1000 reticulocyte counter which utilizes laser flow cytometry. The changes in proportion of RNA-rich reticulocytes (high fluorescence ratio: HFR) and maturation index (MI: HFR + middle fluorescence ratio/low fluorescence ratio) were compared with those of WBC, neutrophil or reticulocyte counts. Engraftment was defined as an HFR of greater than or equal to 5% or a MI of greater than or equal to 15%. Engraftment was confirmed significantly earlier by HFR (13.5 +/- 2.4 days) and MI (13.1 +/- 2.9 days) than by neutrophils (17.1 +/- 3.2 days) or reticulocytes (20.4 +/- 6.2 days). The maturation of reticulocytes would be a useful indicator for engraftment or recovery from marrow aplasia in cases of bone marrow transplantation."} {"id": "PMID:1279235", "title": "[Aplastic anemia successfully treated with erythropoietin and rhG-CSF].", "content": "A 32 year-old female admitted to our hospital with pancytopenia. The hematological data on admission were: RBC: 247 x 10(4)/microliters, Hb: 8.8 g/dl, Plts: 13,000/microliters, WBC: 2,500/microliters. Bone marrow aspirate and biopsied specimen showed marked hypocellularity without infiltration of abnormal cells. A diagnosis of aplastic anemia was made. Neither high-dose methyl-prednisolone pulse therapy nor anti-lymphocyte globulin were effective. With combination of oxymetholone (30 mg/day), recombinant erythropoietin (rHuEpo; 12,000 U/day, three times a week) and recombinant granulocyte-colony simulating factor (rHuG-CSF; 33 micrograms/day) for 3 months, remarkable improvements of hematological data were obtained. Her hemoglobin level reached 11.4 g/dl, and platelets count 49,000/microliters. However, 4 weeks after the withdrawal of erythropoietin and G-CSF administrations, her platelet count fell to 12,000/microliters. It was suggested that combination therapy with erythropoietin and G-CSF were effective for aplastic anemia.", "contents": "[Aplastic anemia successfully treated with erythropoietin and rhG-CSF]. A 32 year-old female admitted to our hospital with pancytopenia. The hematological data on admission were: RBC: 247 x 10(4)/microliters, Hb: 8.8 g/dl, Plts: 13,000/microliters, WBC: 2,500/microliters. Bone marrow aspirate and biopsied specimen showed marked hypocellularity without infiltration of abnormal cells. A diagnosis of aplastic anemia was made. Neither high-dose methyl-prednisolone pulse therapy nor anti-lymphocyte globulin were effective. With combination of oxymetholone (30 mg/day), recombinant erythropoietin (rHuEpo; 12,000 U/day, three times a week) and recombinant granulocyte-colony simulating factor (rHuG-CSF; 33 micrograms/day) for 3 months, remarkable improvements of hematological data were obtained. Her hemoglobin level reached 11.4 g/dl, and platelets count 49,000/microliters. However, 4 weeks after the withdrawal of erythropoietin and G-CSF administrations, her platelet count fell to 12,000/microliters. It was suggested that combination therapy with erythropoietin and G-CSF were effective for aplastic anemia."} {"id": "PMID:1279236", "title": "[Steroid and gamma globulin therapy against virus-associated hemophagocytic syndrome].", "content": "A 21-year-old woman was admitted to our hospital because of high fever, cough, and headache. Other clinical manifestations included hepatosplenomegaly, anemia, leukopenia, and mild liver dysfunction. As she had been diagnosed to have systemic lupus erythematosus (SLE) previously, we first suspected that this disease had become exacerbated. However, the titers of anti-EB virus (VCA-IgG) and some other viruses were high on admission, and hemophagocytosis by macrophages was observed on bone marrow examination. Therefore, she was diagnosed to have virus-associated hemophagocytic syndrome (VAHS). Prednisolone therapy was then initiated, but the patient responded poorly. We next tried gamma globulin, and the clinical findings and laboratory data were improved. Our patient showed a very favourable clinical course following gamma globulin therapy, suggesting that steroid and gamma globulin should be considered as a treatment even in the early stages of this syndrome in adults.", "contents": "[Steroid and gamma globulin therapy against virus-associated hemophagocytic syndrome]. A 21-year-old woman was admitted to our hospital because of high fever, cough, and headache. Other clinical manifestations included hepatosplenomegaly, anemia, leukopenia, and mild liver dysfunction. As she had been diagnosed to have systemic lupus erythematosus (SLE) previously, we first suspected that this disease had become exacerbated. However, the titers of anti-EB virus (VCA-IgG) and some other viruses were high on admission, and hemophagocytosis by macrophages was observed on bone marrow examination. Therefore, she was diagnosed to have virus-associated hemophagocytic syndrome (VAHS). Prednisolone therapy was then initiated, but the patient responded poorly. We next tried gamma globulin, and the clinical findings and laboratory data were improved. Our patient showed a very favourable clinical course following gamma globulin therapy, suggesting that steroid and gamma globulin should be considered as a treatment even in the early stages of this syndrome in adults."} {"id": "PMID:1279237", "title": "[Function, molecular structure and gene expression of interferons].", "content": "Interferon is a key substance of the cytokine network, and is functioning not only as the virus inhibitory factor, but also as the factor for differentiation, development, and homeostasis of animals, including man. The molecular structure, induction mechanisms, interaction with receptor, and antiviral action mechanisms of IFN were reviewed. 1. Molecular structure of IFN IFNs are now divided into 4 types--alpha, beta, gamma, omega--according to antigenicities of IFN proteins, and to base sequence of their genes. The omega type was established officially on 1990 by the Nomenclature Committee of International Society for Interferon Research (ISIR). Also, the genes for HuIFNs were named as follows; HuIFN-A for HuIFN-alpha, HuIFN-B for HuIFN-beta, HuIFN-G for HuIFN-gamma, and HuIFN-W for HuIFN-omega. Nevertheless, the names of Type I IFN and Type II IFN are still valuable, since members of Type I IFN, alpha, beta, and omega, are similar in their molecular structures, and they share the common receptor (Type I IFN receptor), on the other hand, HuIFN-gamma (the only one member of Type II IFN) has different characteristics from the other IFNs, and binds to its specific receptor (Type II IFN receptor). However, it has been reported that both N-terminal and C-terminal of IFN protein of all types, participate in the binding of IFN to its receptor. 2. Induction mechanism of IFN. The factors, IRF-1 and IRF-2, were found to play an important role in IFN induction.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Function, molecular structure and gene expression of interferons]. Interferon is a key substance of the cytokine network, and is functioning not only as the virus inhibitory factor, but also as the factor for differentiation, development, and homeostasis of animals, including man. The molecular structure, induction mechanisms, interaction with receptor, and antiviral action mechanisms of IFN were reviewed. 1. Molecular structure of IFN IFNs are now divided into 4 types--alpha, beta, gamma, omega--according to antigenicities of IFN proteins, and to base sequence of their genes. The omega type was established officially on 1990 by the Nomenclature Committee of International Society for Interferon Research (ISIR). Also, the genes for HuIFNs were named as follows; HuIFN-A for HuIFN-alpha, HuIFN-B for HuIFN-beta, HuIFN-G for HuIFN-gamma, and HuIFN-W for HuIFN-omega. Nevertheless, the names of Type I IFN and Type II IFN are still valuable, since members of Type I IFN, alpha, beta, and omega, are similar in their molecular structures, and they share the common receptor (Type I IFN receptor), on the other hand, HuIFN-gamma (the only one member of Type II IFN) has different characteristics from the other IFNs, and binds to its specific receptor (Type II IFN receptor). However, it has been reported that both N-terminal and C-terminal of IFN protein of all types, participate in the binding of IFN to its receptor. 2. Induction mechanism of IFN. The factors, IRF-1 and IRF-2, were found to play an important role in IFN induction.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279238", "title": "[Function, molecular structure and gene expression of granulocyte colony-stimulating factor].", "content": "Human granulocyte colony-stimulating factor, a 19KD glycoprotein consisting of 174 amino acids, is one of the physiological regulators mainly produced by monocytes-macrophages, fibroblasts, and endothelial cells, under various stimulations such as neutropenias and infections. The molecule specifically and markedly stimulates the production of neutrophils associated with an expansion of the hemopoietic stem cells/progenitor cells, proliferates myeloid leukemia cells, releases these cells into blood, and elevates the functional activities of neutrophils. Under the favor of the activities, recombinant human granulocyte colony-stimulating factor has now become an epoch-making agents for the treatment of various disorders.", "contents": "[Function, molecular structure and gene expression of granulocyte colony-stimulating factor]. Human granulocyte colony-stimulating factor, a 19KD glycoprotein consisting of 174 amino acids, is one of the physiological regulators mainly produced by monocytes-macrophages, fibroblasts, and endothelial cells, under various stimulations such as neutropenias and infections. The molecule specifically and markedly stimulates the production of neutrophils associated with an expansion of the hemopoietic stem cells/progenitor cells, proliferates myeloid leukemia cells, releases these cells into blood, and elevates the functional activities of neutrophils. Under the favor of the activities, recombinant human granulocyte colony-stimulating factor has now become an epoch-making agents for the treatment of various disorders."} {"id": "PMID:1279239", "title": "[Function, molecular structure and gene expression of stem cell factor (SCF)].", "content": "Mice of genotype W/Wv and Sl/Sld have been considered as a model of instinct hemopoietic disorders. W/Wv mice have a defect in hemopoietic stem cells and Sl/Sld mice have a defect in the microenvironment. The W locus in murine chromosome 5 encodes the c-kit proto-oncogene and the Sl locus in chromosome 10 encodes the ligand for c-kit, which has been named stem cell factor (SCF), mast cell growth factor (MGF), kit ligand (KL) and steel factor (SL). The cDNA sequence of SCF suggest that it is synthesized as an integral transmembrane protein and that it has common tertiary structure with M-CSF. SCF enhances the proliferation of hemopoietic stem cells and progenitor cells as well as mast cell in combination with other growth factors. Furthermore, it plays an important role in the proliferation and migration of embryonic stem cell, primordial germ cell and melanocyte.", "contents": "[Function, molecular structure and gene expression of stem cell factor (SCF)]. Mice of genotype W/Wv and Sl/Sld have been considered as a model of instinct hemopoietic disorders. W/Wv mice have a defect in hemopoietic stem cells and Sl/Sld mice have a defect in the microenvironment. The W locus in murine chromosome 5 encodes the c-kit proto-oncogene and the Sl locus in chromosome 10 encodes the ligand for c-kit, which has been named stem cell factor (SCF), mast cell growth factor (MGF), kit ligand (KL) and steel factor (SL). The cDNA sequence of SCF suggest that it is synthesized as an integral transmembrane protein and that it has common tertiary structure with M-CSF. SCF enhances the proliferation of hemopoietic stem cells and progenitor cells as well as mast cell in combination with other growth factors. Furthermore, it plays an important role in the proliferation and migration of embryonic stem cell, primordial germ cell and melanocyte."} {"id": "PMID:1279240", "title": "[Clinical application of hematopoietic growth factor (IL-3, G-CSF, GM-CSF, and EPO)].", "content": "Hematopoietic growth factors were found as factors stimulating hematopoietic colony formation in in vitro culture system using bone marrow cells as a source of hematopoietic progenitor cells. Erythropoietin, a growth factor stimulating erythroid lineage has now been clinically used as an therapeutic agent for anemia of chronic renal failure. Macrophage colony-stimulating factor (M-CSF), a growth factor stimulating the production of leukocytes including monocytes and neutrophils has been clinically used as an agent for leukopenic patients after anti-cancer therapy. M-CSF improves a survival rate after bone marrow transplantation (BMT) through the reduction of mortality rate associated with BMT such as bleeding, engraftment failure and GVHD. M-CSF accelerated platelet production when injected to thrombopenic patients with solid tumor after anticancer therapy. Granulocyte CSF (G-CSF) is a most powerful agent for various kinds of neutropenia such as neutropenia after anti cancer therapy, neutropenia after BMT, aplastic anemia, chronic neutropenia of children and myelodysplastic syndrome. However, since G-CSF stimulates growth of leukemic cells in vitro, careful observations should be required when clinically used on leukemic patients. Clinical studies of granulocyte-macrophage CSF (GM-CSF) and interleukin 3 (IL-3) are now in progress, in which a promoting activity of leukocyte production of these factors is evaluated.", "contents": "[Clinical application of hematopoietic growth factor (IL-3, G-CSF, GM-CSF, and EPO)]. Hematopoietic growth factors were found as factors stimulating hematopoietic colony formation in in vitro culture system using bone marrow cells as a source of hematopoietic progenitor cells. Erythropoietin, a growth factor stimulating erythroid lineage has now been clinically used as an therapeutic agent for anemia of chronic renal failure. Macrophage colony-stimulating factor (M-CSF), a growth factor stimulating the production of leukocytes including monocytes and neutrophils has been clinically used as an agent for leukopenic patients after anti-cancer therapy. M-CSF improves a survival rate after bone marrow transplantation (BMT) through the reduction of mortality rate associated with BMT such as bleeding, engraftment failure and GVHD. M-CSF accelerated platelet production when injected to thrombopenic patients with solid tumor after anticancer therapy. Granulocyte CSF (G-CSF) is a most powerful agent for various kinds of neutropenia such as neutropenia after anti cancer therapy, neutropenia after BMT, aplastic anemia, chronic neutropenia of children and myelodysplastic syndrome. However, since G-CSF stimulates growth of leukemic cells in vitro, careful observations should be required when clinically used on leukemic patients. Clinical studies of granulocyte-macrophage CSF (GM-CSF) and interleukin 3 (IL-3) are now in progress, in which a promoting activity of leukocyte production of these factors is evaluated."} {"id": "PMID:1279241", "title": "[Clinical application of anticancer cytokines].", "content": "The clinical application of anticancer cytokines (interferons, interleukin-1, interleukin-2 and tumor necrosis factor) are reviewed. Although anticancer cytokines have confirmed its usefulness against some tumors which are refractory to the treatment using anticancer drugs, the results of clinical trials have generally been disappointing because the target spectrum and efficiency is somewhat limited. Recently, combined efficacy between interferon and anticancer drugs was reported in some malignancies such as multiple myeloma and colorectal carcinoma. For the development of effective combination treatment, we need more basic and clinical information on dose, schedule and sequence of drug administration.", "contents": "[Clinical application of anticancer cytokines]. The clinical application of anticancer cytokines (interferons, interleukin-1, interleukin-2 and tumor necrosis factor) are reviewed. Although anticancer cytokines have confirmed its usefulness against some tumors which are refractory to the treatment using anticancer drugs, the results of clinical trials have generally been disappointing because the target spectrum and efficiency is somewhat limited. Recently, combined efficacy between interferon and anticancer drugs was reported in some malignancies such as multiple myeloma and colorectal carcinoma. For the development of effective combination treatment, we need more basic and clinical information on dose, schedule and sequence of drug administration."} {"id": "PMID:1279242", "title": "[Interferon therapy of chronic hepatitis].", "content": "The current state of interferon (IFN) therapy for chronic hepatitis B and C in Japan is reviewed. The administration of IFN results in induction of 2'-5' oligoadenylate synthetase (2-5AS). 2-5AS produces 2-5A capable of activating a latent RNAase that degrades viral RNA. In patient with chronic hepatitis B, prominent reduction of HBV DNA, HBe antigen and HBs antigens is observed, when IFN is administered. However, the replication of HBV starts again after stopping of IFN administration, because the effects of IFN do not affect HBV DNA which is the origin of replication. On the other hand, HCV is a RNA virus IFN not only suppresses the production of HCV proteins and its pregenome, but also eradicate HCV RNA that is the origin of replication. In around 40% of the patients with chronic hepatitis C, sustained normalization of ALT and negativity of HCV RNA was obtained after IFN therapy under the most satisfactory regimen.", "contents": "[Interferon therapy of chronic hepatitis]. The current state of interferon (IFN) therapy for chronic hepatitis B and C in Japan is reviewed. The administration of IFN results in induction of 2'-5' oligoadenylate synthetase (2-5AS). 2-5AS produces 2-5A capable of activating a latent RNAase that degrades viral RNA. In patient with chronic hepatitis B, prominent reduction of HBV DNA, HBe antigen and HBs antigens is observed, when IFN is administered. However, the replication of HBV starts again after stopping of IFN administration, because the effects of IFN do not affect HBV DNA which is the origin of replication. On the other hand, HCV is a RNA virus IFN not only suppresses the production of HCV proteins and its pregenome, but also eradicate HCV RNA that is the origin of replication. In around 40% of the patients with chronic hepatitis C, sustained normalization of ALT and negativity of HCV RNA was obtained after IFN therapy under the most satisfactory regimen."} {"id": "PMID:1279243", "title": "[Cytokine therapy of immunodeficiency].", "content": "The cellular immunodeficiency diseases especially those with impaired IL-2 production are successfully treated by every day injection of rhIL-2. IL-2 is also effective on some patients with antibody deficiency probably caused by the lack of T cell help for B cells. Prolonged infection of EB-virus, human immunodeficiency virus, fungi and mycobacteria can be ameliorated by IL-2 treatment. Superoxide production and bacteriocidal activity of the leukocytes from some cases of chronic granulomatous disease are improved by injection of interferon gamma. Succeeding injection of G-CSF is effective to maintain the leukocyte count of congenital neutropenia to the level competent to protect bacterial infections.", "contents": "[Cytokine therapy of immunodeficiency]. The cellular immunodeficiency diseases especially those with impaired IL-2 production are successfully treated by every day injection of rhIL-2. IL-2 is also effective on some patients with antibody deficiency probably caused by the lack of T cell help for B cells. Prolonged infection of EB-virus, human immunodeficiency virus, fungi and mycobacteria can be ameliorated by IL-2 treatment. Superoxide production and bacteriocidal activity of the leukocytes from some cases of chronic granulomatous disease are improved by injection of interferon gamma. Succeeding injection of G-CSF is effective to maintain the leukocyte count of congenital neutropenia to the level competent to protect bacterial infections."} {"id": "PMID:1279244", "title": "High incidence of nuclear accumulation of p53 protein in gastric cancer.", "content": "The accumulation of p53 protein in the nuclei of cancer cells is known to correlate well with the presence of mutations in the p53 gene. We therefore investigated the immunohistochemical reactivity of the anti-p53 antibody, PAb1801, in specimens taken from 149 cases of primary gastric cancer and processed by acetone fixation, in order to elucidate the incidence and clinicopathological significance of p53 alterations in gastric cancer. Thirty-four out of 99 (34%) advanced gastric cancers and 11 out of 50 (22%) early gastric cancers showed positive reactions in the nuclei. The nuclei of non-cancerous cells, including gastric glandular epithelial cells, however, were not stained. Histopathologically, a nuclear accumulation of p53 protein was seen frequently in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures (43/101, 43%), but was rarely seen in signet-ring cell carcinoma, mucinous adenocarcinoma or poorly-differentiated adenocarcinoma growing in a scattered manner (2/48, 4%). There was no correlation between stainability of p53 protein and clinicopathological features such as depth of tumor invasion, microscopic lymphatic invasion, microscopic venous invasion, nodal involvement and clinicopathological stage in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures. The results suggest papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures to share a common carcinogenetic pathway in which mutation of the p53 gene has an important role to play at a relatively early stage. Additionally, we showed the applicability of immunohistochemical detection of p53 protein in endoscopic biopsy material routinely formalin-fixed. The current method may be of some help in routine practice in discriminating between normal, precancerous and cancer cells in the stomach.", "contents": "High incidence of nuclear accumulation of p53 protein in gastric cancer. The accumulation of p53 protein in the nuclei of cancer cells is known to correlate well with the presence of mutations in the p53 gene. We therefore investigated the immunohistochemical reactivity of the anti-p53 antibody, PAb1801, in specimens taken from 149 cases of primary gastric cancer and processed by acetone fixation, in order to elucidate the incidence and clinicopathological significance of p53 alterations in gastric cancer. Thirty-four out of 99 (34%) advanced gastric cancers and 11 out of 50 (22%) early gastric cancers showed positive reactions in the nuclei. The nuclei of non-cancerous cells, including gastric glandular epithelial cells, however, were not stained. Histopathologically, a nuclear accumulation of p53 protein was seen frequently in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures (43/101, 43%), but was rarely seen in signet-ring cell carcinoma, mucinous adenocarcinoma or poorly-differentiated adenocarcinoma growing in a scattered manner (2/48, 4%). There was no correlation between stainability of p53 protein and clinicopathological features such as depth of tumor invasion, microscopic lymphatic invasion, microscopic venous invasion, nodal involvement and clinicopathological stage in papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures. The results suggest papillary adenocarcinoma, well- to moderately-differentiated tubular adenocarcinoma and poorly-differentiated adenocarcinoma with solid nests or focal tubular structures to share a common carcinogenetic pathway in which mutation of the p53 gene has an important role to play at a relatively early stage. Additionally, we showed the applicability of immunohistochemical detection of p53 protein in endoscopic biopsy material routinely formalin-fixed. The current method may be of some help in routine practice in discriminating between normal, precancerous and cancer cells in the stomach."} {"id": "PMID:1279245", "title": "The risk and predictive factors for developing liver cancer among patients with decompensated liver cirrhosis.", "content": "Patients with decompensated liver cirrhosis (n 1441) and those with post-transfusion hepatitis (n 343), whose medical expenses were subsidized by the Aichi Prefectural Government, were followed up for three years by record linkage with the Aichi Cancer Registry. During the follow-up period, 122 incident cases of liver cancer were identified. Compared with the general population, patients with decompensated liver cirrhosis were at a 64.9 times greater risk (50.5 times in males and 100.4 times in females) and those with post-transfusion hepatitis were at a 9.4 times greater risk (8.9 times in males and 13.7 times in females) of developing liver cancer. Information on prognostic factors for 1,068 patients with decompensated liver cirrhosis was also collected in a questionnaire survey by the physicians in charge. Patients positive to hepatitis B surface antigen (HBs Ag) and those positive to HBe Ag had a significantly increased risk of subsequent liver cancer. The risk of developing liver cancer was positively associated with base-line levels of GPT and AFP and age and, inversely associated with total alcohol intake and female sex. In multivariate analyses, the associations with HBe Ag, AFP, sex and age remained statistically significant, whereas the associations with GPT, total alcohol intake and HBs Ag were of borderline significance.", "contents": "The risk and predictive factors for developing liver cancer among patients with decompensated liver cirrhosis. Patients with decompensated liver cirrhosis (n 1441) and those with post-transfusion hepatitis (n 343), whose medical expenses were subsidized by the Aichi Prefectural Government, were followed up for three years by record linkage with the Aichi Cancer Registry. During the follow-up period, 122 incident cases of liver cancer were identified. Compared with the general population, patients with decompensated liver cirrhosis were at a 64.9 times greater risk (50.5 times in males and 100.4 times in females) and those with post-transfusion hepatitis were at a 9.4 times greater risk (8.9 times in males and 13.7 times in females) of developing liver cancer. Information on prognostic factors for 1,068 patients with decompensated liver cirrhosis was also collected in a questionnaire survey by the physicians in charge. Patients positive to hepatitis B surface antigen (HBs Ag) and those positive to HBe Ag had a significantly increased risk of subsequent liver cancer. The risk of developing liver cancer was positively associated with base-line levels of GPT and AFP and age and, inversely associated with total alcohol intake and female sex. In multivariate analyses, the associations with HBe Ag, AFP, sex and age remained statistically significant, whereas the associations with GPT, total alcohol intake and HBs Ag were of borderline significance."} {"id": "PMID:1279246", "title": "[Current status of anti-HCV screening and posttransfusion hepatitis].", "content": "The value of screening blood donors for non-A, non-B Hepatitis using GPT as the surrogate marker has been debated for long time. Since January 1990, Japanese Red Cross Blood Centers have introduced anti-HCV screening with EIA. Approximately 1.1 percent of blood donors screened was anti-HCV positive in Kyushu district. Studies comparing with seroconversion rates showed discrepancy between anti-HCV and anti-HTLV-1 in some regions [Kagoshima: 0.9% (anti-HCV)/5.7% (anti-HTLV-1), Okinawa: 0.7%/5.2%, Nagasaki: 1.0%/3.7%]. Seropositivity of anti-HCV progressively increased with the age and GPT value in both male and female. In blood donors having history of transfusion, anti-HCV reactive rate was more than 10%. Results of Japanese Red Cross Non-A, Non-B Hepatitis Research Group show the effectiveness of implementation of anti-HCV screening to prevent posttransfusion hepatitis.", "contents": "[Current status of anti-HCV screening and posttransfusion hepatitis]. The value of screening blood donors for non-A, non-B Hepatitis using GPT as the surrogate marker has been debated for long time. Since January 1990, Japanese Red Cross Blood Centers have introduced anti-HCV screening with EIA. Approximately 1.1 percent of blood donors screened was anti-HCV positive in Kyushu district. Studies comparing with seroconversion rates showed discrepancy between anti-HCV and anti-HTLV-1 in some regions [Kagoshima: 0.9% (anti-HCV)/5.7% (anti-HTLV-1), Okinawa: 0.7%/5.2%, Nagasaki: 1.0%/3.7%]. Seropositivity of anti-HCV progressively increased with the age and GPT value in both male and female. In blood donors having history of transfusion, anti-HCV reactive rate was more than 10%. Results of Japanese Red Cross Non-A, Non-B Hepatitis Research Group show the effectiveness of implementation of anti-HCV screening to prevent posttransfusion hepatitis."} {"id": "PMID:1279247", "title": "[Clinical study on relationship between hepatocellular carcinoma and hepatitis C virus infection in patients with chronic liver disease].", "content": "The relationship between hepatocellular carcinoma (HCC) and hepatitis C virus (HCV) infection was investigated. Antibody to hepatitis C virus was detected in 88.8% and 87.0% of 240 patients with hepatocellular carcinoma and liver cirrhosis, respectively. A history of blood transfusion was shown in only 21.8% (21/96) of the HCV antibody positive HCC patients. Of 196 patients with chronic hepatitis type C and the HCV antibody positive liver cirrhosis, 10 developed HCC during the follow-up period of two years. A high prevalence of HCV antibody was also shown among 83 patients with alcoholic liver cirrhosis and HCC associated with alcoholic liver cirrhosis. HCV-RNA was detected in all patients with alcoholic HCC. These data support a causal association between hepatitis C virus and hepatocellular carcinoma.", "contents": "[Clinical study on relationship between hepatocellular carcinoma and hepatitis C virus infection in patients with chronic liver disease]. The relationship between hepatocellular carcinoma (HCC) and hepatitis C virus (HCV) infection was investigated. Antibody to hepatitis C virus was detected in 88.8% and 87.0% of 240 patients with hepatocellular carcinoma and liver cirrhosis, respectively. A history of blood transfusion was shown in only 21.8% (21/96) of the HCV antibody positive HCC patients. Of 196 patients with chronic hepatitis type C and the HCV antibody positive liver cirrhosis, 10 developed HCC during the follow-up period of two years. A high prevalence of HCV antibody was also shown among 83 patients with alcoholic liver cirrhosis and HCC associated with alcoholic liver cirrhosis. HCV-RNA was detected in all patients with alcoholic HCC. These data support a causal association between hepatitis C virus and hepatocellular carcinoma."} {"id": "PMID:1279248", "title": "[Diagnosis of hepatitis C and its future].", "content": "Several epitopes of the hepatitis C virus (HCV) have been identified, but the biological and clinical significance of antibodies to each protein is not well understood. Core antigens include C-22, JCC, P 0 and CP-9. Among epitopes in the non structural (NS) regions, C-33C is in the NS3, C100-3 in the NS3/4, 511 in the NS4 and C825 in the NS5 regions. First generation anti-HCV has C100-3 epitope and second generation anti-HCV consists of three epitopes which are C-22, C-33C and C100-3. In order to analyse the clinical significance of the various HCV epitopes, We compared the results of these 9 different HCV specific assays with HCV-RNA, as determined in serum by RT-PCR method using primers to the 5' untranslated region of HCV-RNA. Among 73 patients with chronic NANB liver disease, 94% were positive for C-22, 94% for JCC, 91% for P 0, 89% for CP-9, 97% for C-33C, 84% for C100-3, 65% for 511, 55% for C825, 58% for GOR and 91% for RT-PCR. Positive rates for Core region epitopes were very similar to each other and to the presence of HCV-RNA. Antibodies to NS region epitopes were more variable, with those to NS4 and NS5 region being less sensitive than HCV-RNA. Positivity rates for 537 healthy subjects were 1.1% for C100-3, 2.7% for JCC. 6 persons who were positive for C100-3 were also positive for JCC and 4 of those were positive for HCV-RNA.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Diagnosis of hepatitis C and its future]. Several epitopes of the hepatitis C virus (HCV) have been identified, but the biological and clinical significance of antibodies to each protein is not well understood. Core antigens include C-22, JCC, P 0 and CP-9. Among epitopes in the non structural (NS) regions, C-33C is in the NS3, C100-3 in the NS3/4, 511 in the NS4 and C825 in the NS5 regions. First generation anti-HCV has C100-3 epitope and second generation anti-HCV consists of three epitopes which are C-22, C-33C and C100-3. In order to analyse the clinical significance of the various HCV epitopes, We compared the results of these 9 different HCV specific assays with HCV-RNA, as determined in serum by RT-PCR method using primers to the 5' untranslated region of HCV-RNA. Among 73 patients with chronic NANB liver disease, 94% were positive for C-22, 94% for JCC, 91% for P 0, 89% for CP-9, 97% for C-33C, 84% for C100-3, 65% for 511, 55% for C825, 58% for GOR and 91% for RT-PCR. Positive rates for Core region epitopes were very similar to each other and to the presence of HCV-RNA. Antibodies to NS region epitopes were more variable, with those to NS4 and NS5 region being less sensitive than HCV-RNA. Positivity rates for 537 healthy subjects were 1.1% for C100-3, 2.7% for JCC. 6 persons who were positive for C100-3 were also positive for JCC and 4 of those were positive for HCV-RNA.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279249", "title": "Anti-hypotensive effects of M6434, an orally active alpha 1-adrenoceptor agonist, in rats.", "content": "The anti-hypotensive effects of M6434 were evaluated and compared with those of other orally active sympathomimetics in rats. Oral administration of M6434 (0.5-2.0 mg/kg) and midodrine (1.0-5.0 mg/kg) also produced a dose-related increase in mean arterial pressure in normotensive rats. The pressor effect of M6434 was about 4 times more potent than that of midodrine. Both M6434 and midodrine caused a dose-dependent decrease in heart rate. The pressor effect of M6434 (1.0 mg/kg) did not diminish after its repeated administration for 7 days. The pretreatment with M6434 (0.5-1.0 mg/kg) and midodrine (2.0-5.0 mg/kg) improved the orthostatic index in the experimental model of postural hypotension in rats. The effect of M6434 on postural hypotension was about 5 times more potent than that of midodrine. Intravenously injected M6434 (3-300 micrograms/kg) produced a dose-dependent increase in the blood pressure of pithed rats. These results suggest that M6434 possesses a potent antihypotensive activity which is superior to that of midodrine, and M6434 may be useful in the treatment of essential and postural hypotension.", "contents": "Anti-hypotensive effects of M6434, an orally active alpha 1-adrenoceptor agonist, in rats. The anti-hypotensive effects of M6434 were evaluated and compared with those of other orally active sympathomimetics in rats. Oral administration of M6434 (0.5-2.0 mg/kg) and midodrine (1.0-5.0 mg/kg) also produced a dose-related increase in mean arterial pressure in normotensive rats. The pressor effect of M6434 was about 4 times more potent than that of midodrine. Both M6434 and midodrine caused a dose-dependent decrease in heart rate. The pressor effect of M6434 (1.0 mg/kg) did not diminish after its repeated administration for 7 days. The pretreatment with M6434 (0.5-1.0 mg/kg) and midodrine (2.0-5.0 mg/kg) improved the orthostatic index in the experimental model of postural hypotension in rats. The effect of M6434 on postural hypotension was about 5 times more potent than that of midodrine. Intravenously injected M6434 (3-300 micrograms/kg) produced a dose-dependent increase in the blood pressure of pithed rats. These results suggest that M6434 possesses a potent antihypotensive activity which is superior to that of midodrine, and M6434 may be useful in the treatment of essential and postural hypotension."} {"id": "PMID:1279250", "title": "Ganoderma tsugae mycelium enhances splenic natural killer cell activity and serum interferon production in mice.", "content": "Effects of the water-soluble extract of Ganoderma tsugae mycelium (GT), its alcohol-insoluble subfraction (GTI), and its alcohol-soluble subfraction (GTS) on splenic natural killer (NK) cell activity and serum interferon (IFN) production were assessed in mice. Intraperitoneal administration of GT (4-200 mg/kg) or GTI (1-50 mg/kg), but not GTS, augmented the NK cytotoxic activity in a dose-dependent manner in C3H/HeN mice. This augmentation of splenic NK cytolytic activity was not mouse-strain-dependent. The serum IFN titers of mice were also elevated after i.p.-doses of GTI. The GTI-induced serum IFN was reduced by either IFN-(alpha+beta) antiserum or IFN-gamma monoclonal antibody in vitro. The treatment with antiserum neutralizing IFN-(alpha+beta) resulted in a 70% reduction of GTI-induced IFN, while monoclonal antibody against mouse IFN-gamma, moderately neutralized the GTI-induced IFN (50%). These results demonstrated that both the splenic NK activity and serum IFN [IFN-(alpha+beta) and IFN-gamma] titers are elevated by Ganoderma tsugae mycelium extracts in mice.", "contents": "Ganoderma tsugae mycelium enhances splenic natural killer cell activity and serum interferon production in mice. Effects of the water-soluble extract of Ganoderma tsugae mycelium (GT), its alcohol-insoluble subfraction (GTI), and its alcohol-soluble subfraction (GTS) on splenic natural killer (NK) cell activity and serum interferon (IFN) production were assessed in mice. Intraperitoneal administration of GT (4-200 mg/kg) or GTI (1-50 mg/kg), but not GTS, augmented the NK cytotoxic activity in a dose-dependent manner in C3H/HeN mice. This augmentation of splenic NK cytolytic activity was not mouse-strain-dependent. The serum IFN titers of mice were also elevated after i.p.-doses of GTI. The GTI-induced serum IFN was reduced by either IFN-(alpha+beta) antiserum or IFN-gamma monoclonal antibody in vitro. The treatment with antiserum neutralizing IFN-(alpha+beta) resulted in a 70% reduction of GTI-induced IFN, while monoclonal antibody against mouse IFN-gamma, moderately neutralized the GTI-induced IFN (50%). These results demonstrated that both the splenic NK activity and serum IFN [IFN-(alpha+beta) and IFN-gamma] titers are elevated by Ganoderma tsugae mycelium extracts in mice."} {"id": "PMID:1279251", "title": "Neurokinin A-stimulated phosphoinositide breakdown in rabbit iris sphincter muscle.", "content": "Specific [3H]-substance P binding was saturable and of high affinity (KD = 2.5 nM) with a Bmax of 725 fmol/mg protein in the isolated rabbit iris sphincter muscle. The competition for [3H]-substance P binding was in the order of eledoisin greater than substance P greater than kassinin greater than neurokinin B greater than neurokinin A greater than physalaemin. In the same preparation, neurokinin A, as well as substance P induced a concentration-related accumulation of [3H]-inositol phosphates (IPs), and the maximum increase was about 200% of the control at 10(-4) M. [D-Arg1, D-Trp7,9, Leu11]-substance P (SP) and [D-Pro2, D-Trp7,9]-SP (10(-3) M) inhibited substance P or neurokinin A (10(-4) M)-induced phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis significantly. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP (10(-3) M) also inhibited neurokinin A (10(-4) M)-induced PIP2 hydrolysis significantly. Neurokinin A and substance P produced concentration-related contractions in normal Ca(2+)-containing medium. The contractile response was weaker in Ca(2+)-free medium, and there was no response in 0.2 mM EGTA medium. In Ca(2+)-free medium, the basal level of [3H]-IPs accumulation was smaller than that in normal medium, and neurokinin A and substance P significantly increased PIP2 hydrolysis. In the 0.2 mM EGTA containing medium, neurokinin A and substance P did not stimulate the PIP2 hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Neurokinin A-stimulated phosphoinositide breakdown in rabbit iris sphincter muscle. Specific [3H]-substance P binding was saturable and of high affinity (KD = 2.5 nM) with a Bmax of 725 fmol/mg protein in the isolated rabbit iris sphincter muscle. The competition for [3H]-substance P binding was in the order of eledoisin greater than substance P greater than kassinin greater than neurokinin B greater than neurokinin A greater than physalaemin. In the same preparation, neurokinin A, as well as substance P induced a concentration-related accumulation of [3H]-inositol phosphates (IPs), and the maximum increase was about 200% of the control at 10(-4) M. [D-Arg1, D-Trp7,9, Leu11]-substance P (SP) and [D-Pro2, D-Trp7,9]-SP (10(-3) M) inhibited substance P or neurokinin A (10(-4) M)-induced phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis significantly. [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP (10(-3) M) also inhibited neurokinin A (10(-4) M)-induced PIP2 hydrolysis significantly. Neurokinin A and substance P produced concentration-related contractions in normal Ca(2+)-containing medium. The contractile response was weaker in Ca(2+)-free medium, and there was no response in 0.2 mM EGTA medium. In Ca(2+)-free medium, the basal level of [3H]-IPs accumulation was smaller than that in normal medium, and neurokinin A and substance P significantly increased PIP2 hydrolysis. In the 0.2 mM EGTA containing medium, neurokinin A and substance P did not stimulate the PIP2 hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279252", "title": "Effect of AS-35 on agonist-induced contractions and the resting tonus of airway smooth muscles and the in vitro release of chemical mediators from passively sensitized lung fragments from humans and guinea pigs.", "content": "Effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]-3-(1H-tetrazol -5-yl)-4H-pyrido[1,2-alpha]pyrimidin-4-one (AS-35) on the resting tonus or contractions induced by agonists, such as leukotriene (LT) D4 and specific antigen of isolated guinea pig tracheas or human bronchi, and the in vitro anaphylactic release of histamine and LTs from human lung fragments were investigated and compared with the effects of FPL 55712 and disodium cromoglycate. AS-35 as well as FPL 55712 did not affect the contractions induced by acetylcholine and histamine of the isolated guinea pig trachea. However, the compound at relatively low concentrations obviously inhibited contractions induced by LTD4, and the antagonistic activity was stronger than that of FPL 55712. Treatment of the isolated human bronchus with AS-35 tended to induce the inhibition of both LTD4- and antigen-induced contractions and the relaxation of the resting tonus in a concentration-dependent manner. The inhibitory potency at 10(-6) g/ml was slightly stronger than that of FPL 55712, but this was not statistically significant. The anaphylactic release of histamine and LTs from the lung fragments appeared to be inhibited by the treatment with AS-35 5 min prior to the antigen challenge. From these results, it is suggested that AS-35 is effective against allergic asthma through antagonism towards peptide-LTs released anaphylactically in addition to inhibition of the chemical mediator release.", "contents": "Effect of AS-35 on agonist-induced contractions and the resting tonus of airway smooth muscles and the in vitro release of chemical mediators from passively sensitized lung fragments from humans and guinea pigs. Effects of 9-[(4-acetyl-3-hydroxy-2-n-propylphenoxy)methyl]-3-(1H-tetrazol -5-yl)-4H-pyrido[1,2-alpha]pyrimidin-4-one (AS-35) on the resting tonus or contractions induced by agonists, such as leukotriene (LT) D4 and specific antigen of isolated guinea pig tracheas or human bronchi, and the in vitro anaphylactic release of histamine and LTs from human lung fragments were investigated and compared with the effects of FPL 55712 and disodium cromoglycate. AS-35 as well as FPL 55712 did not affect the contractions induced by acetylcholine and histamine of the isolated guinea pig trachea. However, the compound at relatively low concentrations obviously inhibited contractions induced by LTD4, and the antagonistic activity was stronger than that of FPL 55712. Treatment of the isolated human bronchus with AS-35 tended to induce the inhibition of both LTD4- and antigen-induced contractions and the relaxation of the resting tonus in a concentration-dependent manner. The inhibitory potency at 10(-6) g/ml was slightly stronger than that of FPL 55712, but this was not statistically significant. The anaphylactic release of histamine and LTs from the lung fragments appeared to be inhibited by the treatment with AS-35 5 min prior to the antigen challenge. From these results, it is suggested that AS-35 is effective against allergic asthma through antagonism towards peptide-LTs released anaphylactically in addition to inhibition of the chemical mediator release."} {"id": "PMID:1279253", "title": "Nebracetam (WEB 1881FU) prevents N-methyl-D-aspartate receptor-mediated neurotoxicity in rat striatal slices.", "content": "The effects of nebracetam were investigated on N-methyl-D-aspartate (NMDA) receptor- and voltage-operated Ca2+ channels (VOCC)-mediated neural dysfunction by directly monitoring the real-time dynamics of dopamine released from rat striatal slices. Nebracetam (10(-5) and 10(-4) M) completely protected against striatal dopaminergic impairment induced by L-glutamate and NMDA, respectively. BAY K-8644-evoked striatal dysfunction was not blocked by nebracetam (10(-4) M). Therefore, nebracetam seems to produce a neuroprotective action by interacting, at least in part, with NMDA receptor-operated Ca2+ channels.", "contents": "Nebracetam (WEB 1881FU) prevents N-methyl-D-aspartate receptor-mediated neurotoxicity in rat striatal slices. The effects of nebracetam were investigated on N-methyl-D-aspartate (NMDA) receptor- and voltage-operated Ca2+ channels (VOCC)-mediated neural dysfunction by directly monitoring the real-time dynamics of dopamine released from rat striatal slices. Nebracetam (10(-5) and 10(-4) M) completely protected against striatal dopaminergic impairment induced by L-glutamate and NMDA, respectively. BAY K-8644-evoked striatal dysfunction was not blocked by nebracetam (10(-4) M). Therefore, nebracetam seems to produce a neuroprotective action by interacting, at least in part, with NMDA receptor-operated Ca2+ channels."} {"id": "PMID:1279254", "title": "Isolation of substance P binding protein from rat brain.", "content": "Substance P (SP) binding protein of rat brain was solubilized by digitonin. The solubilized proteins were then purified by sequential gel filtration, concanavalin A lectin Sepharose, and SP-affinity chromatography. The calculated molecular weight of this purified SP binding protein was 76-74 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The rabbits were immunized with the purified protein and resulting polyclonal anti-sera were tested. The immune serum significantly inhibited [3H]SP binding to the 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate solubilized membrane fractions from rat brain, whereas pre-bleed antiserum failed to inhibit the binding. This polyclonal antibody also inhibited the activity of 45Ca influx into astroglioma cells stimulated by SP, but does not inhibit that stimulated by histamine. Furthermore, this polyclonal antibody recognized the 76-74 kDa band as assessed by Western blotting. These data strongly suggest that this polyclonal antibody could recognize a part of the natural SP receptor site.", "contents": "Isolation of substance P binding protein from rat brain. Substance P (SP) binding protein of rat brain was solubilized by digitonin. The solubilized proteins were then purified by sequential gel filtration, concanavalin A lectin Sepharose, and SP-affinity chromatography. The calculated molecular weight of this purified SP binding protein was 76-74 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The rabbits were immunized with the purified protein and resulting polyclonal anti-sera were tested. The immune serum significantly inhibited [3H]SP binding to the 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate solubilized membrane fractions from rat brain, whereas pre-bleed antiserum failed to inhibit the binding. This polyclonal antibody also inhibited the activity of 45Ca influx into astroglioma cells stimulated by SP, but does not inhibit that stimulated by histamine. Furthermore, this polyclonal antibody recognized the 76-74 kDa band as assessed by Western blotting. These data strongly suggest that this polyclonal antibody could recognize a part of the natural SP receptor site."} {"id": "PMID:1279255", "title": "Relaxant response of isolated basilar arteries to calcitonin gene-related peptide in stroke-prone spontaneously hypertensive rats.", "content": "The relaxant effects of calcitonin gene-related peptide (CGRP) and other drugs were compared in basilar artery rings obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). In addition, the relaxant effect of CGRP on basilar arteries from spontaneously hypertensive rats (SHR) was examined. Relaxation induced by CGRP was independent of the presence of endothelium, and it was markedly increased in SHRSP when compared to WKY. In contrast, acetylcholine-induced relaxation was endothelium-dependent and did not differ between the two groups. Enhanced CGRP-induced relaxation was also found in SHR when compared to WKY. However, the relaxant response was greater in SHRSP than in SHR. No significant differences were found in the relaxation induced by isoproterenol, forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine in endothelium-rubbed arteries of WKY and SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the rat basilar artery, and that the enhanced CGRP-induced relaxation found in SHRSP may not be associated with alterations of vasodilation mediated by cyclic AMP.", "contents": "Relaxant response of isolated basilar arteries to calcitonin gene-related peptide in stroke-prone spontaneously hypertensive rats. The relaxant effects of calcitonin gene-related peptide (CGRP) and other drugs were compared in basilar artery rings obtained from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). In addition, the relaxant effect of CGRP on basilar arteries from spontaneously hypertensive rats (SHR) was examined. Relaxation induced by CGRP was independent of the presence of endothelium, and it was markedly increased in SHRSP when compared to WKY. In contrast, acetylcholine-induced relaxation was endothelium-dependent and did not differ between the two groups. Enhanced CGRP-induced relaxation was also found in SHR when compared to WKY. However, the relaxant response was greater in SHRSP than in SHR. No significant differences were found in the relaxation induced by isoproterenol, forskolin, dibutyryl cyclic AMP, and 3-isobutyl-1-methylxanthine in endothelium-rubbed arteries of WKY and SHRSP. These results suggest that CGRP produces endothelium-independent relaxation in the rat basilar artery, and that the enhanced CGRP-induced relaxation found in SHRSP may not be associated with alterations of vasodilation mediated by cyclic AMP."} {"id": "PMID:1279257", "title": "[Granulocyte colony-stimulating factor producing lung large cell carcinoma with sarcomatous transformation].", "content": "We report a case of granulocyte colony-stimulating factor (G-CSF) producing lung large cell carcinoma with sarcomatous transformation. A 57-year-old man was admitted for evaluation of an abnormal shadow near the right pulmonary hilus on chest X-ray film. Brush cytology specimen from right B6 disclosed large cell carcinoma. His clinical stage was already IIIB (T3N3M0) on admission, so we immediately administered chemotherapy and radiation therapy. However, the patient's condition gradually deteriorated and he died of respiratory failure. Although there was no evidence of infection throughout his clinical course, his peripheral white blood cell count gradually increased and reached 47,000/mm3 (neutrophils 96%) before death. Histological study of the autopsy specimen revealed that the primary tumor was composed of two different elements (large cell carcinoma and spindle cell sarcomatoid element). The spindle cell sarcomatoid element appeared to have arisen from sarcomatous transformation of carcinoma cells, because the transition margin of the carcinoma to the sarcomatoid element was smooth, and special and immunohistochemical staining of both elements showed the same properties. Moreover, immunohistochemical study with monoclonal antibody to human G-CSF, 4A6 clearly demonstrated granular staining of G-CSF in the cytoplasm of tumor cells.", "contents": "[Granulocyte colony-stimulating factor producing lung large cell carcinoma with sarcomatous transformation]. We report a case of granulocyte colony-stimulating factor (G-CSF) producing lung large cell carcinoma with sarcomatous transformation. A 57-year-old man was admitted for evaluation of an abnormal shadow near the right pulmonary hilus on chest X-ray film. Brush cytology specimen from right B6 disclosed large cell carcinoma. His clinical stage was already IIIB (T3N3M0) on admission, so we immediately administered chemotherapy and radiation therapy. However, the patient's condition gradually deteriorated and he died of respiratory failure. Although there was no evidence of infection throughout his clinical course, his peripheral white blood cell count gradually increased and reached 47,000/mm3 (neutrophils 96%) before death. Histological study of the autopsy specimen revealed that the primary tumor was composed of two different elements (large cell carcinoma and spindle cell sarcomatoid element). The spindle cell sarcomatoid element appeared to have arisen from sarcomatous transformation of carcinoma cells, because the transition margin of the carcinoma to the sarcomatoid element was smooth, and special and immunohistochemical staining of both elements showed the same properties. Moreover, immunohistochemical study with monoclonal antibody to human G-CSF, 4A6 clearly demonstrated granular staining of G-CSF in the cytoplasm of tumor cells."} {"id": "PMID:1279258", "title": "[Adjuvant chemotherapy with MVP-CAB (methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin and bleomycin) for epithelial tumors of the upper urinary tract].", "content": "Surgery plus adjuvant chemotherapy using MVP-CAB (Day 1; methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg, Day 2; cisplatinum 50 mg/m2) was conducted in 12 patients with epithelial tumors of the upper urinary tract who had unfavorable prognostic factors (progressive disease which was pT2 or more, or transitional cell carcinoma of grade 2 and 3). The MVP-CAB regimen was as follows: A total of 3 cycles were given either before or after surgery. MVP-CAB was given at 3- to 4-week intervals before surgery, or after surgery if the patient had macroscopic residual lesions. For the patients with micrometastases detected after radical surgery, MVP-CAB was given every 1 to 2 months. The median survival period of the 10 patients who underwent radical surgery was 17 months (5-59 months). The three-year survival rate of these 10 patients (Kaplan-Meier method) was 100% in grade 2 (5 patients), 100% in progressive cancer greater than pT3 (6), and 80% in grade 3 (5). In two patients, residual macroscopic lesions after surgery were confirmed. One of them initially responded to MVP-CAB but died of cancer 21 months later, while the other one did not respond and died of cancer 8 months later. Two renal pelvis cancer patients for whom radical surgery was considered impossible due to distant metastases showed remarkable tumor reduction after MVP-CAB administration (one showed CR for liver metastases and the other showed PR for lymph node metastases).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Adjuvant chemotherapy with MVP-CAB (methotrexate, vincristine, cisplatinum, cyclophosphamide, adriamycin and bleomycin) for epithelial tumors of the upper urinary tract]. Surgery plus adjuvant chemotherapy using MVP-CAB (Day 1; methotrexate 20 mg/m2, vincristine 0.6 mg/m2, cyclophosphamide 500 mg/m2, adriamycin 20 mg/m2, and bleomycin 30 mg, Day 2; cisplatinum 50 mg/m2) was conducted in 12 patients with epithelial tumors of the upper urinary tract who had unfavorable prognostic factors (progressive disease which was pT2 or more, or transitional cell carcinoma of grade 2 and 3). The MVP-CAB regimen was as follows: A total of 3 cycles were given either before or after surgery. MVP-CAB was given at 3- to 4-week intervals before surgery, or after surgery if the patient had macroscopic residual lesions. For the patients with micrometastases detected after radical surgery, MVP-CAB was given every 1 to 2 months. The median survival period of the 10 patients who underwent radical surgery was 17 months (5-59 months). The three-year survival rate of these 10 patients (Kaplan-Meier method) was 100% in grade 2 (5 patients), 100% in progressive cancer greater than pT3 (6), and 80% in grade 3 (5). In two patients, residual macroscopic lesions after surgery were confirmed. One of them initially responded to MVP-CAB but died of cancer 21 months later, while the other one did not respond and died of cancer 8 months later. Two renal pelvis cancer patients for whom radical surgery was considered impossible due to distant metastases showed remarkable tumor reduction after MVP-CAB administration (one showed CR for liver metastases and the other showed PR for lymph node metastases).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279259", "title": "[Intra-arterial COMPA chemotherapy for invasive bladder cancer].", "content": "We presented 12 patients with invasive bladder cancer treated by the subselective intra-arterial COMPA chemotherapy. COMPA was administered up to an average of 3.3 courses (ranged from 2 to 6 courses) every 2 or 3 weeks, consisting of cisplatin: 15 mg/M2 on days 4 and 5; vincristine (oncovin): 0.6 mg/M2 on days 1 and 2; methotrexate: 5 mg/M2 on days 2 and 3; peplomycin: 5 mg/body on days 1, 2 and 3; and adriamycin: 10 mg/M2 on day 4. These were injected through a teflon catheter the tip of which was placed just proximal to the aortic bifurcation, and another tip was led through a subcutaneous tunnel from the inguinally punctured area to the anterior chest wall. The 12 patients, 7 men and 5 women, ranged in age from 53 to 73 (mean: 67) years. Histopathologically 11 had transitional cell carcinoma and one had adenocarcinoma. Malignant gradings were grade 2 in 8 patients, and grade 3 in 4. The stagings were T2 in 3 patients, T3 in 5, T4 in 4 and only one had bony metastasis. Of the 12 patients, 10 were alive at the last follow-up with a mean duration of 36 months (range: 16 to 49). Six patients achieved a complete remission, four achieved a partial remission and two were stable. One died of ileus after 16 months and another of progression after 36 months. All the patients received post-chemotherapeutic adjunctive therapies, which were transurethral resection, partial cystectomy, radiation and/or intravesical instillation. The toxicities were not severe, but anorexia, nausea, vomiting, hair loss, numbness of fingers and/or toes, subileus, and leukopenia were noticed.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Intra-arterial COMPA chemotherapy for invasive bladder cancer]. We presented 12 patients with invasive bladder cancer treated by the subselective intra-arterial COMPA chemotherapy. COMPA was administered up to an average of 3.3 courses (ranged from 2 to 6 courses) every 2 or 3 weeks, consisting of cisplatin: 15 mg/M2 on days 4 and 5; vincristine (oncovin): 0.6 mg/M2 on days 1 and 2; methotrexate: 5 mg/M2 on days 2 and 3; peplomycin: 5 mg/body on days 1, 2 and 3; and adriamycin: 10 mg/M2 on day 4. These were injected through a teflon catheter the tip of which was placed just proximal to the aortic bifurcation, and another tip was led through a subcutaneous tunnel from the inguinally punctured area to the anterior chest wall. The 12 patients, 7 men and 5 women, ranged in age from 53 to 73 (mean: 67) years. Histopathologically 11 had transitional cell carcinoma and one had adenocarcinoma. Malignant gradings were grade 2 in 8 patients, and grade 3 in 4. The stagings were T2 in 3 patients, T3 in 5, T4 in 4 and only one had bony metastasis. Of the 12 patients, 10 were alive at the last follow-up with a mean duration of 36 months (range: 16 to 49). Six patients achieved a complete remission, four achieved a partial remission and two were stable. One died of ileus after 16 months and another of progression after 36 months. All the patients received post-chemotherapeutic adjunctive therapies, which were transurethral resection, partial cystectomy, radiation and/or intravesical instillation. The toxicities were not severe, but anorexia, nausea, vomiting, hair loss, numbness of fingers and/or toes, subileus, and leukopenia were noticed.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279260", "title": "[A single session of transurethral microwave thermotherapy for benign prostatic hyperplasia].", "content": "A single session of transurethral microwave thermotherapy using Prostatron (Technomed International, France) was performed in 20 patients with benign prostatic hyperplasia, and the clinical efficacy of this modality was evaluated by analysing the subjective and objective responses following the treatment. 1,296 MHz microwaves are delivered to the prostate by an antenna placed in a 20 Fr urethral balloon catheter equipped with a cooling system for preservation of the urethral mucosa. The treatment was performed in a single session for an hour on an outpatient basis. The clinical efficacy was evaluated by a total score of subjective symptoms and objective findings including residual urine and average flow rate, 8 weeks after the treatment. Reduction of subjective symptom score was observed in 26 cases (86.7%), and that of objective findings in 21 (70%). When 25% or more decrease of the total score was defined as good, the overall good result including subjective and objective responses was seen in 24 cases (80%). During the treatment and follow-up period, no severe adverse effect was detected. In conclusion, a single session of thermotherapy by Prostatron is a safe and useful modality as a non-surgical treatment performed on an outpatient basis for benign prostatic hyperplasia.", "contents": "[A single session of transurethral microwave thermotherapy for benign prostatic hyperplasia]. A single session of transurethral microwave thermotherapy using Prostatron (Technomed International, France) was performed in 20 patients with benign prostatic hyperplasia, and the clinical efficacy of this modality was evaluated by analysing the subjective and objective responses following the treatment. 1,296 MHz microwaves are delivered to the prostate by an antenna placed in a 20 Fr urethral balloon catheter equipped with a cooling system for preservation of the urethral mucosa. The treatment was performed in a single session for an hour on an outpatient basis. The clinical efficacy was evaluated by a total score of subjective symptoms and objective findings including residual urine and average flow rate, 8 weeks after the treatment. Reduction of subjective symptom score was observed in 26 cases (86.7%), and that of objective findings in 21 (70%). When 25% or more decrease of the total score was defined as good, the overall good result including subjective and objective responses was seen in 24 cases (80%). During the treatment and follow-up period, no severe adverse effect was detected. In conclusion, a single session of thermotherapy by Prostatron is a safe and useful modality as a non-surgical treatment performed on an outpatient basis for benign prostatic hyperplasia."} {"id": "PMID:1279261", "title": "[Significance of prostatic specific antigen in the mass screening for prostate cancer].", "content": "The significance of prostatic specific antigen (PSA) was investigated in the subjects examined by the mass screening for prostate cancer from 1985 to 1990. All subjects was examined by digital rectal examination (DRE) and with prostatic acid phosphatase (PAP) and the subjects in whom prostate cancer (Pca) was suspected from abnormal DRE and/or elevated PAP were recommended to receive the secondary screening to confirm the presence of Pca. PSA was measured by radioimmunoassay using Ball-Elsa-PSA-kit. 1,600 serum samples were obtained from our serum bank. The relationship among PSA, prostate size estimated by DRE and age was investigated. PSA was increased with age and the prostate size, PSA being more closely related with the latter. Therefore, we estimated that PSA has an ability to detect benign prostatic hypertrophy (BPH) in the mass screening. This estimation should be confirmed by using an ultrasound tomography because the prostate size obtained by DRE is inaccurate as compared with that obtained by ultrasound tomography. The cut off level of PSA was determined by control which was composed from the subjects with normal size prostate and one with BPH. When the cut off level was 8.6 ng/ml, the sensitivity, specificity and efficiency as Pca marker was 73.9%, 97.4% and 97.1%, respectively. PSA was more than 8.6 ng/ml in all of Pca with elevated PAP. PSA was expected to improve the Pca detection rate in our mass screening system.", "contents": "[Significance of prostatic specific antigen in the mass screening for prostate cancer]. The significance of prostatic specific antigen (PSA) was investigated in the subjects examined by the mass screening for prostate cancer from 1985 to 1990. All subjects was examined by digital rectal examination (DRE) and with prostatic acid phosphatase (PAP) and the subjects in whom prostate cancer (Pca) was suspected from abnormal DRE and/or elevated PAP were recommended to receive the secondary screening to confirm the presence of Pca. PSA was measured by radioimmunoassay using Ball-Elsa-PSA-kit. 1,600 serum samples were obtained from our serum bank. The relationship among PSA, prostate size estimated by DRE and age was investigated. PSA was increased with age and the prostate size, PSA being more closely related with the latter. Therefore, we estimated that PSA has an ability to detect benign prostatic hypertrophy (BPH) in the mass screening. This estimation should be confirmed by using an ultrasound tomography because the prostate size obtained by DRE is inaccurate as compared with that obtained by ultrasound tomography. The cut off level of PSA was determined by control which was composed from the subjects with normal size prostate and one with BPH. When the cut off level was 8.6 ng/ml, the sensitivity, specificity and efficiency as Pca marker was 73.9%, 97.4% and 97.1%, respectively. PSA was more than 8.6 ng/ml in all of Pca with elevated PAP. PSA was expected to improve the Pca detection rate in our mass screening system."} {"id": "PMID:1279262", "title": "[Three-dimensional display of the prostate based on transrectal ultrasonogram].", "content": "A software for a lap top computer to display prostatic contour three-dimensionally based on transrectal ultrasonograms was developed, and its clinical usefulness was examined. The prostatic contour of a case with prostatic cancer showed a typical irregular surface, and that of a case with prostatic hypertrophy had a smooth spherical shape, while that of a normal case had a flat shape. Each showed its characteristic shape. Estimation of the prostatic weight by assuming that the prostatic contour has ellipsoidal contour is a simple method for prostatic weight measurement, but it has a tendency to underestimate the weights, especially in normal cases. Three-dimensional display of the contour of prostatic cancer, prostatic hypertrophy, and normal prostate revealed that it could be estimated as ellipsoid in prostatic cancer or hypertrophy, while the normal prostatic contour was too flat to be calculated as such. Among 52 patients with benign prostatic hypertrophy who underwent transrectal ultrasonotomography before and during the anti-androgen therapy more than three time, nine cases showed transient reduction of more than 30% in prostatic weight and then reenlargement of more than 30%. In these cases, three-dimensional display of prostatic contour was done. The display was useful to visualize clearly which part reenlarged. Therefore, usefulness of the three-dimensional display of the prostate was verified.", "contents": "[Three-dimensional display of the prostate based on transrectal ultrasonogram]. A software for a lap top computer to display prostatic contour three-dimensionally based on transrectal ultrasonograms was developed, and its clinical usefulness was examined. The prostatic contour of a case with prostatic cancer showed a typical irregular surface, and that of a case with prostatic hypertrophy had a smooth spherical shape, while that of a normal case had a flat shape. Each showed its characteristic shape. Estimation of the prostatic weight by assuming that the prostatic contour has ellipsoidal contour is a simple method for prostatic weight measurement, but it has a tendency to underestimate the weights, especially in normal cases. Three-dimensional display of the contour of prostatic cancer, prostatic hypertrophy, and normal prostate revealed that it could be estimated as ellipsoid in prostatic cancer or hypertrophy, while the normal prostatic contour was too flat to be calculated as such. Among 52 patients with benign prostatic hypertrophy who underwent transrectal ultrasonotomography before and during the anti-androgen therapy more than three time, nine cases showed transient reduction of more than 30% in prostatic weight and then reenlargement of more than 30%. In these cases, three-dimensional display of prostatic contour was done. The display was useful to visualize clearly which part reenlarged. Therefore, usefulness of the three-dimensional display of the prostate was verified."} {"id": "PMID:1279263", "title": "[The surgical treatment of malignant liver tumors].", "content": "From study of the data concerning 133 patients who underwent operation for tumor of the liver the authors found that 43 (32.2%) patients were treated by a radical operation and 34 (25.5%) were subjected to palliative interventions. Among the radical interventions hemihepatectomy was performed on 21 (48.8%) patients. The total number of complications after radical operations was 46.3%, the mortality rate 11.6%. The authors discuss problems of the prevention of some complications, intraoperative hemorrhages in the first place. Different variants of bile diversion accounted for most of the palliative interventions. Survival in radical operations was 38.56 months, in palliative operations 8.34 months, and in exploratory operations 5.9 months.", "contents": "[The surgical treatment of malignant liver tumors]. From study of the data concerning 133 patients who underwent operation for tumor of the liver the authors found that 43 (32.2%) patients were treated by a radical operation and 34 (25.5%) were subjected to palliative interventions. Among the radical interventions hemihepatectomy was performed on 21 (48.8%) patients. The total number of complications after radical operations was 46.3%, the mortality rate 11.6%. The authors discuss problems of the prevention of some complications, intraoperative hemorrhages in the first place. Different variants of bile diversion accounted for most of the palliative interventions. Survival in radical operations was 38.56 months, in palliative operations 8.34 months, and in exploratory operations 5.9 months."} {"id": "PMID:1279264", "title": "[Reoperations in primary rectal cancer].", "content": "The authors studied the results of repeated radical operations performed in 73 patients who had been subjected earlier to exploratory and palliative operations. During repeated interventions radical operations were conducted on 54 (74%) patients which were of a combined character in 11 (20.4%) of them. Localized-radical palliative resections and extirpations in the presence of remote metastases were performed on 3 (4.1%) patients. Palliative operations were carried out on 16 (21.9%) patients. Postoperative mortality was 6.8%. The data provides evidence that the performance of repeated operations is expedient and justified because they make it possible to raise the resectability index among patients with rectal carcinoma.", "contents": "[Reoperations in primary rectal cancer]. The authors studied the results of repeated radical operations performed in 73 patients who had been subjected earlier to exploratory and palliative operations. During repeated interventions radical operations were conducted on 54 (74%) patients which were of a combined character in 11 (20.4%) of them. Localized-radical palliative resections and extirpations in the presence of remote metastases were performed on 3 (4.1%) patients. Palliative operations were carried out on 16 (21.9%) patients. Postoperative mortality was 6.8%. The data provides evidence that the performance of repeated operations is expedient and justified because they make it possible to raise the resectability index among patients with rectal carcinoma."} {"id": "PMID:1279267", "title": "Plasma lipoproteins and monocyte-macrophages in a peroxisome-deficient system: study of a patient with infantile refsum disease.", "content": "Hypocholesterolaemia in infantile Refsum disease (IRD) may link peroxisomes and lipoprotein metabolism. In our patient, plasma cholesterol levels were reduced to 26% and 29% of control in LDL and HDL fractions, respectively. Plasma apolipoproteins B-100 and A-I levels were 52% and 66% of controls, respectively. In the kindred, plasma cholesterol concentration was 61-73% of controls. The HDL-cholesterol/apo A-I ratios were: patient 0.12; kindred 0.17; controls 0.28. Analysis of the IRD patient's lipoprotein revealed compositional abnormalities in all fractions. The patient's LDL demonstrated a substantial reduction in its lipid-to-protein ratio. Alterations in plasma lipoproteins affect their interaction with macrophages. Upon incubation of the patient's LDL with J-774 macrophages, its cellular uptake, measured as cholesterol esterification rate, was only 66% of a control rate. The abnormal LDL of the IRD patient showed also only 25% of control susceptibility to in vitro oxidation. Studies of cellular cholesterol metabolism in the patient's monocyte-derived macrophages (MDM) showed 57% increased cholesterol esterification rate in comparison to normal MDM. The possible link between lipoprotein abnormalities and monocyte-macrophage cholesterol metabolism is discussed.", "contents": "Plasma lipoproteins and monocyte-macrophages in a peroxisome-deficient system: study of a patient with infantile refsum disease. Hypocholesterolaemia in infantile Refsum disease (IRD) may link peroxisomes and lipoprotein metabolism. In our patient, plasma cholesterol levels were reduced to 26% and 29% of control in LDL and HDL fractions, respectively. Plasma apolipoproteins B-100 and A-I levels were 52% and 66% of controls, respectively. In the kindred, plasma cholesterol concentration was 61-73% of controls. The HDL-cholesterol/apo A-I ratios were: patient 0.12; kindred 0.17; controls 0.28. Analysis of the IRD patient's lipoprotein revealed compositional abnormalities in all fractions. The patient's LDL demonstrated a substantial reduction in its lipid-to-protein ratio. Alterations in plasma lipoproteins affect their interaction with macrophages. Upon incubation of the patient's LDL with J-774 macrophages, its cellular uptake, measured as cholesterol esterification rate, was only 66% of a control rate. The abnormal LDL of the IRD patient showed also only 25% of control susceptibility to in vitro oxidation. Studies of cellular cholesterol metabolism in the patient's monocyte-derived macrophages (MDM) showed 57% increased cholesterol esterification rate in comparison to normal MDM. The possible link between lipoprotein abnormalities and monocyte-macrophage cholesterol metabolism is discussed."} {"id": "PMID:1279265", "title": "[Laboratory diagnosis of tumors of the pancreato-biliary area in patients with mechanical jaundice].", "content": "Blood investigation of tumor markers CA-19-9, carcinoembryonic antigen and alpha-fetoprotein was performed in patients with mechanical jaundice due to tumor involvement of the pancreatobiliary area and a nontumor process. It was concluded that the use of CA-19-9-marker and carcinoembryonic antigen provided a successful differential diagnosis between jaundice resultant from tumor and nontumor diseases. Alpha-fetoprotein turned to be of no informative value. Analysis of tumor markers contents in patients with pancreatobiliary tumors demonstrated the usefulness of them in the preoperative assessment of surgical intervention practicability.", "contents": "[Laboratory diagnosis of tumors of the pancreato-biliary area in patients with mechanical jaundice]. Blood investigation of tumor markers CA-19-9, carcinoembryonic antigen and alpha-fetoprotein was performed in patients with mechanical jaundice due to tumor involvement of the pancreatobiliary area and a nontumor process. It was concluded that the use of CA-19-9-marker and carcinoembryonic antigen provided a successful differential diagnosis between jaundice resultant from tumor and nontumor diseases. Alpha-fetoprotein turned to be of no informative value. Analysis of tumor markers contents in patients with pancreatobiliary tumors demonstrated the usefulness of them in the preoperative assessment of surgical intervention practicability."} {"id": "PMID:1279268", "title": "Expression of acidic fibroblast growth factor in regenerating liver and during hepatic differentiation.", "content": "Acidic fibroblast growth factor belongs to a family of growth factors that show a high affinity for heparin sulfate proteoglycans. In vitro, it participates in various cellular functions including proliferation, differentiation, angiogenesis, and cell migration, but in vivo, the physiologic role of this growth factor is still not clearly defined. The level of expression and also cellular distribution of transcripts for acidic fibroblast growth factor (aFGF) were studied in adult rat liver after partial hepatectomy and during hepatic differentiation in fetal, neonatal, and adult livers by Northern analysis and in situ hybridization techniques. After partial hepatectomy a significant increase in the transcripts for aFGF was observed at 24 hours, whereas at 4 and 12 hours after the operation, the level of transcripts were similar to those of sham-operated animals. In the postnatal liver a high level of aFGF expression was present when the most evident transition from 2 to 3 cell thick hepatic cords to normal hepatic structure is taking place (Ogawa K, Medine A, Farber E. Br J Cancer 1979;40: 782-90). In contrast during the prenatal period, when the liver is still a hemopoietic organ and only a small number of sinusoids are present, low level of aFGF transcripts could be found. Animals treated with 2-acetylaminofluorene and partial hepatectomy (Evarts RP, Nagy P, Marsden E, Thorgeirsson SS. Carcinogenesis 1987;8:1737-40) displayed a marked increase in hepatic aFGF transcripts at the peak of proliferation of primitive liver epithelial cells (oval cells) and perisinusoidal stellate cells (Ito cells) in addition to hepatocytes. In situ hybridization combined with immunocytochemistry using oval and Ito cell specific antibodies revealed the presence of transcripts both in oval cells and Ito cells. Basophilic areas composed of small hepatocytes had a 3-fold increase in the level of transcripts as compared with the surrounding hepatocytes. These experiments demonstrate that the expression of aFGF is highest during the late stages of hepatic morphogenesis in newborn animals as well as during hepatic differentiation in adult liver.", "contents": "Expression of acidic fibroblast growth factor in regenerating liver and during hepatic differentiation. Acidic fibroblast growth factor belongs to a family of growth factors that show a high affinity for heparin sulfate proteoglycans. In vitro, it participates in various cellular functions including proliferation, differentiation, angiogenesis, and cell migration, but in vivo, the physiologic role of this growth factor is still not clearly defined. The level of expression and also cellular distribution of transcripts for acidic fibroblast growth factor (aFGF) were studied in adult rat liver after partial hepatectomy and during hepatic differentiation in fetal, neonatal, and adult livers by Northern analysis and in situ hybridization techniques. After partial hepatectomy a significant increase in the transcripts for aFGF was observed at 24 hours, whereas at 4 and 12 hours after the operation, the level of transcripts were similar to those of sham-operated animals. In the postnatal liver a high level of aFGF expression was present when the most evident transition from 2 to 3 cell thick hepatic cords to normal hepatic structure is taking place (Ogawa K, Medine A, Farber E. Br J Cancer 1979;40: 782-90). In contrast during the prenatal period, when the liver is still a hemopoietic organ and only a small number of sinusoids are present, low level of aFGF transcripts could be found. Animals treated with 2-acetylaminofluorene and partial hepatectomy (Evarts RP, Nagy P, Marsden E, Thorgeirsson SS. Carcinogenesis 1987;8:1737-40) displayed a marked increase in hepatic aFGF transcripts at the peak of proliferation of primitive liver epithelial cells (oval cells) and perisinusoidal stellate cells (Ito cells) in addition to hepatocytes. In situ hybridization combined with immunocytochemistry using oval and Ito cell specific antibodies revealed the presence of transcripts both in oval cells and Ito cells. Basophilic areas composed of small hepatocytes had a 3-fold increase in the level of transcripts as compared with the surrounding hepatocytes. These experiments demonstrate that the expression of aFGF is highest during the late stages of hepatic morphogenesis in newborn animals as well as during hepatic differentiation in adult liver."} {"id": "PMID:1279269", "title": "Markers of complement-dependent and complement-independent glomerular visceral epithelial cell injury in vivo. Expression of antiadhesive proteins and cytoskeletal changes.", "content": "Visceral glomerular epithelial cells (GEC) are an important component of the glomerular filtration barrier to proteins. While ultrastructural GEC changes have frequently been observed in proteinuric states, no suitable light microscopic markers of GEC injury have yet been identified. We have analyzed in vivo the GEC expression of proteins known to be involved in cell shape changes. SPARC (osteonectin, BM-40) and tenascin (cytotactin, J1, hexabrachion) belong to a group of anti-adhesive glycoproteins, that modulate cell-matrix interactions. We also studied cytoskeletal intermediate filament proteins, including desmin and vimentin. The GEC expression of SPARC, tenascin, desmin, and vimentin was analyzed in various types of GEC injury in the rat, including complement-mediated injury (passive Heymann nephritis, autologous immune complex nephritis, conA anti-conA nephritis), complement-independent injury (nephrotoxic nephritis), toxic injury (aminonucleoside nephrosis) and hypertensive injury (5/6 nephrectomy, angiotensin-II infusion). A complement-mediated model of mesangial cell injury (anti-Thy 1.1 mesangial proliferative nephritis) served as a control. SPARC mRNA and protein were constitutively expressed in normal rat glomeruli. Immunostaining and immunoelectron microscopy primarily localized SPARC to the cytoplasm of GEC. Markedly increased glomerular SPARC synthesis and GEC immunostaining was observed in all instances of complement-mediated GEC injury but in none of the other conditions. In contrast, glomerular immunostaining for tenascin, that also stained in a GEC pattern, either remained unchanged or increased to a minor degree (complement-mediated models). GEC immunostaining for desmin in normal rats was low and variable, and increased significantly in any form of GEC injury but not in anti-Thy 1.1 nephritis. No concomitant increase of GEC immunostaining for vimentin was detectable, which could have been due to the constitutively high expression of vimentin in GEC. SPARC and desmin, but not tenascin or vimentin, are suitable light microscopic markers of GEC injury. The combined staining for these proteins may be useful in differentiating the mechanisms of GEC injury.", "contents": "Markers of complement-dependent and complement-independent glomerular visceral epithelial cell injury in vivo. Expression of antiadhesive proteins and cytoskeletal changes. Visceral glomerular epithelial cells (GEC) are an important component of the glomerular filtration barrier to proteins. While ultrastructural GEC changes have frequently been observed in proteinuric states, no suitable light microscopic markers of GEC injury have yet been identified. We have analyzed in vivo the GEC expression of proteins known to be involved in cell shape changes. SPARC (osteonectin, BM-40) and tenascin (cytotactin, J1, hexabrachion) belong to a group of anti-adhesive glycoproteins, that modulate cell-matrix interactions. We also studied cytoskeletal intermediate filament proteins, including desmin and vimentin. The GEC expression of SPARC, tenascin, desmin, and vimentin was analyzed in various types of GEC injury in the rat, including complement-mediated injury (passive Heymann nephritis, autologous immune complex nephritis, conA anti-conA nephritis), complement-independent injury (nephrotoxic nephritis), toxic injury (aminonucleoside nephrosis) and hypertensive injury (5/6 nephrectomy, angiotensin-II infusion). A complement-mediated model of mesangial cell injury (anti-Thy 1.1 mesangial proliferative nephritis) served as a control. SPARC mRNA and protein were constitutively expressed in normal rat glomeruli. Immunostaining and immunoelectron microscopy primarily localized SPARC to the cytoplasm of GEC. Markedly increased glomerular SPARC synthesis and GEC immunostaining was observed in all instances of complement-mediated GEC injury but in none of the other conditions. In contrast, glomerular immunostaining for tenascin, that also stained in a GEC pattern, either remained unchanged or increased to a minor degree (complement-mediated models). GEC immunostaining for desmin in normal rats was low and variable, and increased significantly in any form of GEC injury but not in anti-Thy 1.1 nephritis. No concomitant increase of GEC immunostaining for vimentin was detectable, which could have been due to the constitutively high expression of vimentin in GEC. SPARC and desmin, but not tenascin or vimentin, are suitable light microscopic markers of GEC injury. The combined staining for these proteins may be useful in differentiating the mechanisms of GEC injury."} {"id": "PMID:1279270", "title": "A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor.", "content": "Blood vessel growth is necessary for normal tissue homeostatis and contributes to solid tumor growth. Methods to quantitate neovascularization should be useful in testing biological factors and drugs that regulate angiogenesis or to induce a vascular supply to promote wound healing. An extract of basement membrane proteins (Matrigel) was found to reconstitute into a gel when injected subcutaneously into C57/BL mice and to support an intense vascular response when supplemented with angiogenic factors. New vessels and von Willebrand factor antigen staining were apparent in the gel 2-3 days after injection, reaching a maximum after 3-5 days. Hemoglobin content of the gels was found to parallel the increase in vessels in the gel allowing ready quantitation. Angiogenesis was obtained with both acidic and basic fibroblast growth factors and was enhanced by heparin. Several substances were tested for angiostatic activity in this assay by coinjection in Matrigel with fibroblast growth factor and heparin. Platelet-derived growth factor BB, interleukin 1-beta, interleukin-6, and transforming growth factor-beta were potent inhibitors of neovascularization induced by fibroblast growth factor. Tumor necrosis factor-alpha did not alter the response but was alone a potent inducer of neovascularization when coinjected with Matrigel and heparin. Consistent with the previously demonstrated importance of collagenase in mediating endothelial cell invasion, a tissue inhibitor of metalloproteinases that also inhibits collagenases was found to be a potent inhibitor of fibroblast growth factor-induced angiogenesis. Our assay allows the ready quantitative assessment of angiogenic and anti-angiogenic factors and should be useful in the isolation of endothelial cells from the capillaries that penetrate into the gel.", "contents": "A simple, quantitative method for assessing angiogenesis and antiangiogenic agents using reconstituted basement membrane, heparin, and fibroblast growth factor. Blood vessel growth is necessary for normal tissue homeostatis and contributes to solid tumor growth. Methods to quantitate neovascularization should be useful in testing biological factors and drugs that regulate angiogenesis or to induce a vascular supply to promote wound healing. An extract of basement membrane proteins (Matrigel) was found to reconstitute into a gel when injected subcutaneously into C57/BL mice and to support an intense vascular response when supplemented with angiogenic factors. New vessels and von Willebrand factor antigen staining were apparent in the gel 2-3 days after injection, reaching a maximum after 3-5 days. Hemoglobin content of the gels was found to parallel the increase in vessels in the gel allowing ready quantitation. Angiogenesis was obtained with both acidic and basic fibroblast growth factors and was enhanced by heparin. Several substances were tested for angiostatic activity in this assay by coinjection in Matrigel with fibroblast growth factor and heparin. Platelet-derived growth factor BB, interleukin 1-beta, interleukin-6, and transforming growth factor-beta were potent inhibitors of neovascularization induced by fibroblast growth factor. Tumor necrosis factor-alpha did not alter the response but was alone a potent inducer of neovascularization when coinjected with Matrigel and heparin. Consistent with the previously demonstrated importance of collagenase in mediating endothelial cell invasion, a tissue inhibitor of metalloproteinases that also inhibits collagenases was found to be a potent inhibitor of fibroblast growth factor-induced angiogenesis. Our assay allows the ready quantitative assessment of angiogenic and anti-angiogenic factors and should be useful in the isolation of endothelial cells from the capillaries that penetrate into the gel."} {"id": "PMID:1279271", "title": "Pathways of macromolecular tracer transport across venules and small veins. Structural basis for the hyperpermeability of tumor blood vessels.", "content": "Blood vessels supplying tumors are hyperpermeable to macromolecules, but the mechanisms responsible are poorly understood. To investigate the structural basis for the leakiness of tumor blood vessels, we performed a transmission electron microscopic study of three syngeneic transplantable carcinomas (mouse ovarian carcinoma and the line 1 and line 10 bile duct guinea pig carcinomas) at early intervals after intravenous injection of several macromolecular tracers. Tracers with widely differing physical properties were studied: horseradish peroxidase, ferritin, 150 kilodalton fluorescein isothiocyanate-dextran and gold-bovine serum albumin. All tracers leaked primarily from venules and small veins at the tumor-host interface, for the most part vessels lined by a continuous endothelium. The predominant pathway by which all four tracers exited venules in all three tumors was by way of a system of smooth membrane-bound, interconnecting vesicles and vacuoles; these tended to cluster together at irregular intervals in the endothelial cell cytoplasm to form organelle-like structures, vesiculo-vacuolar organelles (VVO). In favorable sections, VVO interfaced with both the luminal and abluminal surfaces of endothelial cells. HRP alone crossed venules and small veins through apposed inter-endothelial cell junctions. Tracers also exited vessels by way of endothelial fenestrae where these occurred (rarely) in mouse ovarian tumor-associated venules. VVO occurred with similar frequency and complexity in the continuous endothelium-lined venules and small veins that supplied the normal subcutis of either tumor-bearing or control animals. As in tumor-associated vessels, VVO provided the predominant pathway by which all four tracers exited normal vessels, but VVO labeling and extravasation were both much greater in tumor than in control vessels (p < 0.001 for ferritin). VVO are prominent structures in both tumor-supplying and control vessel endothelial cells and provide the primary pathway for macromolecular extravasation. The large increase in permeability characteristic of tumor vessels is likely attributable to upregulation of VVO function.", "contents": "Pathways of macromolecular tracer transport across venules and small veins. Structural basis for the hyperpermeability of tumor blood vessels. Blood vessels supplying tumors are hyperpermeable to macromolecules, but the mechanisms responsible are poorly understood. To investigate the structural basis for the leakiness of tumor blood vessels, we performed a transmission electron microscopic study of three syngeneic transplantable carcinomas (mouse ovarian carcinoma and the line 1 and line 10 bile duct guinea pig carcinomas) at early intervals after intravenous injection of several macromolecular tracers. Tracers with widely differing physical properties were studied: horseradish peroxidase, ferritin, 150 kilodalton fluorescein isothiocyanate-dextran and gold-bovine serum albumin. All tracers leaked primarily from venules and small veins at the tumor-host interface, for the most part vessels lined by a continuous endothelium. The predominant pathway by which all four tracers exited venules in all three tumors was by way of a system of smooth membrane-bound, interconnecting vesicles and vacuoles; these tended to cluster together at irregular intervals in the endothelial cell cytoplasm to form organelle-like structures, vesiculo-vacuolar organelles (VVO). In favorable sections, VVO interfaced with both the luminal and abluminal surfaces of endothelial cells. HRP alone crossed venules and small veins through apposed inter-endothelial cell junctions. Tracers also exited vessels by way of endothelial fenestrae where these occurred (rarely) in mouse ovarian tumor-associated venules. VVO occurred with similar frequency and complexity in the continuous endothelium-lined venules and small veins that supplied the normal subcutis of either tumor-bearing or control animals. As in tumor-associated vessels, VVO provided the predominant pathway by which all four tracers exited normal vessels, but VVO labeling and extravasation were both much greater in tumor than in control vessels (p < 0.001 for ferritin). VVO are prominent structures in both tumor-supplying and control vessel endothelial cells and provide the primary pathway for macromolecular extravasation. The large increase in permeability characteristic of tumor vessels is likely attributable to upregulation of VVO function."} {"id": "PMID:1279272", "title": "Loss of expression of protectin (CD59) is associated with complement membrane attack complex deposition in myocardial infarction.", "content": "Protectin (CD59) is a recently discovered inhibitor of the complement membrane attack complex (MAC). In the present study we investigated expression of protectin in human heart and examined the relationship between MAC deposition and protectin in myocardial infarction. Myocardial tissue specimens were obtained at autopsy from patients who had died of myocardial infarction (n = 10) or other causes (n = 5). MAC and protectin were detected by indirect immunofluorescence microscopy analysis in the heart sections by using antibodies against individual components of MAC, MAC neoantigens and protectin. Myocardial protectin was purified by affinity chromatography and compared with the previously characterized erythrocyte and urinary protectins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, N-terminal amino acid sequencing, and testing its ability to bind to the terminal complement complex. The possible glycophosphoinositol-type anchorage of protectin in the heart was examined by treating myocardial sections with glycophosphoinositol-specific phospholipase C. Immunoblotting and immunofluorescence analysis showed expression of protectin in the sarcolemmal membranes of normal myocardium. Protectin purified from normal human heart tissue had the same molecular weight and N-terminal amino acid sequence as CD59 purified from urine. In sucrose density ultracentrifugation analysis it was observed to bind efficiently to the SC5b-8 complex. In normal myocardium the expression of CD59 was sensitive to treatment with glycophosphoinositol-specific phospholipase C. The expression of CD59 was lost or clearly diminished in infarcted lesions aged 1-14 days. Loss of CD59 expression was accompanied by concomitant deposition of the MAC within the CD59-negative lesions. In border areas between an infarcted lesion and normal tissue, CD59 often appeared in small vesicles, suggesting shedding as a possible mechanism for its removal. Glycophosphoinositol-anchored CD59 is expressed in the sarcolemmal membranes of normal heart but lost from infarcted myocardium. Acquired loss of resistance to autologous complement and subsequent complement attack may thus be involved in the pathophysiology of myocardial infarction.", "contents": "Loss of expression of protectin (CD59) is associated with complement membrane attack complex deposition in myocardial infarction. Protectin (CD59) is a recently discovered inhibitor of the complement membrane attack complex (MAC). In the present study we investigated expression of protectin in human heart and examined the relationship between MAC deposition and protectin in myocardial infarction. Myocardial tissue specimens were obtained at autopsy from patients who had died of myocardial infarction (n = 10) or other causes (n = 5). MAC and protectin were detected by indirect immunofluorescence microscopy analysis in the heart sections by using antibodies against individual components of MAC, MAC neoantigens and protectin. Myocardial protectin was purified by affinity chromatography and compared with the previously characterized erythrocyte and urinary protectins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, N-terminal amino acid sequencing, and testing its ability to bind to the terminal complement complex. The possible glycophosphoinositol-type anchorage of protectin in the heart was examined by treating myocardial sections with glycophosphoinositol-specific phospholipase C. Immunoblotting and immunofluorescence analysis showed expression of protectin in the sarcolemmal membranes of normal myocardium. Protectin purified from normal human heart tissue had the same molecular weight and N-terminal amino acid sequence as CD59 purified from urine. In sucrose density ultracentrifugation analysis it was observed to bind efficiently to the SC5b-8 complex. In normal myocardium the expression of CD59 was sensitive to treatment with glycophosphoinositol-specific phospholipase C. The expression of CD59 was lost or clearly diminished in infarcted lesions aged 1-14 days. Loss of CD59 expression was accompanied by concomitant deposition of the MAC within the CD59-negative lesions. In border areas between an infarcted lesion and normal tissue, CD59 often appeared in small vesicles, suggesting shedding as a possible mechanism for its removal. Glycophosphoinositol-anchored CD59 is expressed in the sarcolemmal membranes of normal heart but lost from infarcted myocardium. Acquired loss of resistance to autologous complement and subsequent complement attack may thus be involved in the pathophysiology of myocardial infarction."} {"id": "PMID:1279273", "title": "Effects of training on muscle capillary pattern: intermittent vs continuous exercise.", "content": "The effects of two exercise regimens (intermittent and continuous endurance) on the fiber area, and capillarization of mice skeletal muscle (gastrocnemius) was studied. The training programs had a duration of 30 days, 5 days/week, and was performed on a motor-driven treadmill. The intermittent group performed the exercise at 16 m.min-1 with a slope of 5%. The continuous group performed the exercise at 16 m.min-1 with 0%. The fiber area and the capillarization was evaluated in the white portion of the gastrocnemius. A high degree of hypertrophy was observed, and a significant increase in the capillary density, capillary to fiber ratio, and in the number of capillaries sectioned obliquely and/or longitudinally was found. The results suggest that the endurance training, intermittent or continuous, induce cell hypertrophy, and an increase in capillarization especially, based on an alteration of the structural pattern.", "contents": "Effects of training on muscle capillary pattern: intermittent vs continuous exercise. The effects of two exercise regimens (intermittent and continuous endurance) on the fiber area, and capillarization of mice skeletal muscle (gastrocnemius) was studied. The training programs had a duration of 30 days, 5 days/week, and was performed on a motor-driven treadmill. The intermittent group performed the exercise at 16 m.min-1 with a slope of 5%. The continuous group performed the exercise at 16 m.min-1 with 0%. The fiber area and the capillarization was evaluated in the white portion of the gastrocnemius. A high degree of hypertrophy was observed, and a significant increase in the capillary density, capillary to fiber ratio, and in the number of capillaries sectioned obliquely and/or longitudinally was found. The results suggest that the endurance training, intermittent or continuous, induce cell hypertrophy, and an increase in capillarization especially, based on an alteration of the structural pattern."} {"id": "PMID:1279274", "title": "Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells.", "content": "Gut-associated lymphoid cells are modulated by several gut hormones. We postulated that lymphokine-associated-killer (LAK) cell cytotoxicity of lymphocytes isolated from the gut mucosa may be increased by substance P (SP). Intestinal lamina propria mononuclear cells (LPMC) and colonic cancer cells were isolated from operative specimens by successive mechanical and enzymatic dissociation methods. Effector LAK cells were induced by culturing LPMC with recombinant interleukin-2 at a concentration of 250 U/ml. Substance P (10(-5) M) was added to the culture medium. Targets consisted of fresh colon cancer cells, HT-29 (cultured human colon cancer cell line), and control cell lines. After 4 days of incubation, cytotoxicity was measured using a 4-h 51Cr release assay. LAK cells alone showed moderate cytotoxicity against HT-29 and none against fresh colon cancer cells. LAK cells generated in the presence of substance P showed moderate cytotoxicity against HT-29 and strong cytotoxicity against fresh colorectal cancer cells. The percentage of cytotoxicity +/- SEM at various effector to target ratios was [(*) denotes P < 0.05 compared with above]: [table: see text] We conclude that substance P significantly increases LAK cell cytotoxicity against fresh colon cancer cells, but not against cultured cells.", "contents": "Substance P increases in vitro lymphokine-activated-killer (LAK) cell cytotoxicity against fresh colorectal cancer cells. Gut-associated lymphoid cells are modulated by several gut hormones. We postulated that lymphokine-associated-killer (LAK) cell cytotoxicity of lymphocytes isolated from the gut mucosa may be increased by substance P (SP). Intestinal lamina propria mononuclear cells (LPMC) and colonic cancer cells were isolated from operative specimens by successive mechanical and enzymatic dissociation methods. Effector LAK cells were induced by culturing LPMC with recombinant interleukin-2 at a concentration of 250 U/ml. Substance P (10(-5) M) was added to the culture medium. Targets consisted of fresh colon cancer cells, HT-29 (cultured human colon cancer cell line), and control cell lines. After 4 days of incubation, cytotoxicity was measured using a 4-h 51Cr release assay. LAK cells alone showed moderate cytotoxicity against HT-29 and none against fresh colon cancer cells. LAK cells generated in the presence of substance P showed moderate cytotoxicity against HT-29 and strong cytotoxicity against fresh colorectal cancer cells. The percentage of cytotoxicity +/- SEM at various effector to target ratios was [(*) denotes P < 0.05 compared with above]: [table: see text] We conclude that substance P significantly increases LAK cell cytotoxicity against fresh colon cancer cells, but not against cultured cells."} {"id": "PMID:1279275", "title": "Protease activation following reperfusion of porcine pancreatic allografts.", "content": "To study the degree of protease activation at reperfusion of a pancreatic allograft after cold storage for 24 hr, 18 porcine whole-organ pancreaticoduodenal allograft transplantations were performed. Twelve grafts were flushed with and stored in Perfadex. In six of these, a hyperosmotic salt solution was injected into the graft aorta at reperfusion. Six grafts were flushed and stored in UW solution. Eleven of twelve grafts in the Perfadex groups were functioning on the first postoperative day, compared with one of six in the UW solution group. There was a significantly more pronounced protease activation among grafts stored in UW solution than in the other groups, with a subsequent breakthrough of the local protease protection barrier made up of protease inhibitors. In surviving pigs (n = 14), biochemical signs of protease activation evolved in plasma, including formation of trypsin-protease inhibitor complexes, a decline in C3 and kininogen levels, and a decline in functionally active alpha 2-macroglobulin, functionally active antithrombin III, and plasma kallikrein inhibitory activity. These biochemical signs of pancreatitis correlated with a deteriorated graft function on the second postoperative day, indicating that graft tissue damage occurred due to protease activation.", "contents": "Protease activation following reperfusion of porcine pancreatic allografts. To study the degree of protease activation at reperfusion of a pancreatic allograft after cold storage for 24 hr, 18 porcine whole-organ pancreaticoduodenal allograft transplantations were performed. Twelve grafts were flushed with and stored in Perfadex. In six of these, a hyperosmotic salt solution was injected into the graft aorta at reperfusion. Six grafts were flushed and stored in UW solution. Eleven of twelve grafts in the Perfadex groups were functioning on the first postoperative day, compared with one of six in the UW solution group. There was a significantly more pronounced protease activation among grafts stored in UW solution than in the other groups, with a subsequent breakthrough of the local protease protection barrier made up of protease inhibitors. In surviving pigs (n = 14), biochemical signs of protease activation evolved in plasma, including formation of trypsin-protease inhibitor complexes, a decline in C3 and kininogen levels, and a decline in functionally active alpha 2-macroglobulin, functionally active antithrombin III, and plasma kallikrein inhibitory activity. These biochemical signs of pancreatitis correlated with a deteriorated graft function on the second postoperative day, indicating that graft tissue damage occurred due to protease activation."} {"id": "PMID:1279276", "title": "Administration of tumor necrosis factor alpha (TNF alpha) inhibitors after exposure to TNF alpha prevents development of the maximal biological effect: an argument for clinical treatment with TNF alpha inhibitors.", "content": "The cytokine tumor necrosis factor alpha (TNF alpha) is involved in the pathophysiology of a wide variety of diseases. Pretreatment with anti-TNF alpha antibodies has proven its success in animal models of disease. The question, however, whether intervention with anti-TNF alpha antibodies might be useful in the clinical situation in which TNF alpha is already produced is still unanswered. We therefore studied the relation between the duration of TNF alpha/TNF receptor interaction and the extent of the induced biological effects in two different in vitro systems: (1) the slowly induced cytotoxicity of the TNF-sensitive murine cell line L929, and (2) the rapid TNF alpha-induced expression of an adhesion molecule for the polymorphonuclear cell, ELAM-1 on human endothelial cells. The TNF alpha/TNF receptor interaction was interrupted at different times after onset of stimulation, either by washing away TNF alpha or by adding TNF alpha activity-blocking monoclonal antibody. To establish an optimal effect for both TNF alpha-induced cytotoxicity on L929 cells and TNF alpha-induced expression of ELAM-1 on human endothelial cells, the TNF receptor had to be occupied by TNF alpha for at least 30-60% of the full incubation period. This observation provides an argument that clinical intervention with TNF alpha inhibitors can be advantageous, even in a situation in which TNF alpha has already been released into the circulation.", "contents": "Administration of tumor necrosis factor alpha (TNF alpha) inhibitors after exposure to TNF alpha prevents development of the maximal biological effect: an argument for clinical treatment with TNF alpha inhibitors. The cytokine tumor necrosis factor alpha (TNF alpha) is involved in the pathophysiology of a wide variety of diseases. Pretreatment with anti-TNF alpha antibodies has proven its success in animal models of disease. The question, however, whether intervention with anti-TNF alpha antibodies might be useful in the clinical situation in which TNF alpha is already produced is still unanswered. We therefore studied the relation between the duration of TNF alpha/TNF receptor interaction and the extent of the induced biological effects in two different in vitro systems: (1) the slowly induced cytotoxicity of the TNF-sensitive murine cell line L929, and (2) the rapid TNF alpha-induced expression of an adhesion molecule for the polymorphonuclear cell, ELAM-1 on human endothelial cells. The TNF alpha/TNF receptor interaction was interrupted at different times after onset of stimulation, either by washing away TNF alpha or by adding TNF alpha activity-blocking monoclonal antibody. To establish an optimal effect for both TNF alpha-induced cytotoxicity on L929 cells and TNF alpha-induced expression of ELAM-1 on human endothelial cells, the TNF receptor had to be occupied by TNF alpha for at least 30-60% of the full incubation period. This observation provides an argument that clinical intervention with TNF alpha inhibitors can be advantageous, even in a situation in which TNF alpha has already been released into the circulation."} {"id": "PMID:1279277", "title": "In vitro and ex vivo inhibition of the modification of low-density lipoprotein by indapamide.", "content": "The effect of an antihypertensive drug, indapamide, on copper- and endothelial cell-induced peroxidation of human low-density lipoprotein (LDL) was studied and compared with that of drugs previously shown to protect LDL against peroxidation: probucol and vitamin E and other thiazidic and nonthiazidic diuretics (clopamide, hydrochlorothiazide, and furosemide). Incubation with indapamide inhibited in a dose-dependent manner LDL peroxidation induced either by copper ions or by cultured endothelial cells. Both electrophoretic mobility and thiobarbituric acid-reactive substances (TBARS) content of LDL returned to almost normal values in the presence of 1 microM indapamide. This drug was at least 10 times more potent than probucol and vitamin E in inhibiting LDL peroxidation. No inhibitory effect has been observed with clopamide, hydrochlorothiazide, and furosemide in the same experimental conditions. Homozygote Watanabe rabbits were treated orally with indapamide (10 mg/kg/d for 3 days) to evaluate the potential protective effect of the compound on LDL peroxidation in vivo. Purified LDL from placebo and treated rabbits were submitted to peroxidation induced by copper ions, and indapamide was effectively able to protect LDL in these experimental conditions. This effect was especially obvious 6 and 8 h after the start of the incubation when LDL of the placebo-treated animals were modified. The mechanism of action of these drugs was examined in vitro using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) test and in kinetic studies of arachidonic acid photoperoxidation. Indapamide as well as vitamin E and probucol were effective free radical scavengers, but the other diuretic molecules were not.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "In vitro and ex vivo inhibition of the modification of low-density lipoprotein by indapamide. The effect of an antihypertensive drug, indapamide, on copper- and endothelial cell-induced peroxidation of human low-density lipoprotein (LDL) was studied and compared with that of drugs previously shown to protect LDL against peroxidation: probucol and vitamin E and other thiazidic and nonthiazidic diuretics (clopamide, hydrochlorothiazide, and furosemide). Incubation with indapamide inhibited in a dose-dependent manner LDL peroxidation induced either by copper ions or by cultured endothelial cells. Both electrophoretic mobility and thiobarbituric acid-reactive substances (TBARS) content of LDL returned to almost normal values in the presence of 1 microM indapamide. This drug was at least 10 times more potent than probucol and vitamin E in inhibiting LDL peroxidation. No inhibitory effect has been observed with clopamide, hydrochlorothiazide, and furosemide in the same experimental conditions. Homozygote Watanabe rabbits were treated orally with indapamide (10 mg/kg/d for 3 days) to evaluate the potential protective effect of the compound on LDL peroxidation in vivo. Purified LDL from placebo and treated rabbits were submitted to peroxidation induced by copper ions, and indapamide was effectively able to protect LDL in these experimental conditions. This effect was especially obvious 6 and 8 h after the start of the incubation when LDL of the placebo-treated animals were modified. The mechanism of action of these drugs was examined in vitro using the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) test and in kinetic studies of arachidonic acid photoperoxidation. Indapamide as well as vitamin E and probucol were effective free radical scavengers, but the other diuretic molecules were not.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279278", "title": "Pharmacokinetics and pharmacodynamics of benazepril in hypertensive patients with normal and impaired renal function.", "content": "The pharmacokinetics and pharmacodynamics of benazepril, an angiotensin converting enzyme (ACE) inhibitor, were investigated after administration of a single oral 5-mg dose and 7 more doses on consecutive days to hypertensive patients with normal renal function (NRF) and those with impaired renal function (IRF). The antihypertensive effect of benazepril was observed as early as 30 min after a single dose, and those effects during consecutive dosing were also sustained for 24 h with a lesser diurnal variation in blood pressure (BP). The time to peak (Tmax) and the apparent elimination half-life (t1/2) for benazepril were 0.6-0.7 h and 0.4-0.8 h, respectively. Tmax for its diacid was 1.5-2.4 h in both groups. The area under the plasma concentration-time curve to 24 h (AUC0-24h) for the diacid was significantly greater in the IRF group than in the NRF group. After consecutive dosing of benazepril, AUC0-24h and plasma peak level (Cmax) were significantly increased in the IRF group. Serum ACE activity was markedly suppressed for 24 h after administration, and the inhibition was closely related to plasma diacid levels. A significant inverse correlation was observed between creatinine clearance and the AUC for the diacid. These results suggest that benazepril is rapidly bioactivated to diacid and exhibits rapid onset and long-lasting antihypertensive effects. Dosage reduction might be required to minimize unnecessary drug accumulation in patients with severe IRF.", "contents": "Pharmacokinetics and pharmacodynamics of benazepril in hypertensive patients with normal and impaired renal function. The pharmacokinetics and pharmacodynamics of benazepril, an angiotensin converting enzyme (ACE) inhibitor, were investigated after administration of a single oral 5-mg dose and 7 more doses on consecutive days to hypertensive patients with normal renal function (NRF) and those with impaired renal function (IRF). The antihypertensive effect of benazepril was observed as early as 30 min after a single dose, and those effects during consecutive dosing were also sustained for 24 h with a lesser diurnal variation in blood pressure (BP). The time to peak (Tmax) and the apparent elimination half-life (t1/2) for benazepril were 0.6-0.7 h and 0.4-0.8 h, respectively. Tmax for its diacid was 1.5-2.4 h in both groups. The area under the plasma concentration-time curve to 24 h (AUC0-24h) for the diacid was significantly greater in the IRF group than in the NRF group. After consecutive dosing of benazepril, AUC0-24h and plasma peak level (Cmax) were significantly increased in the IRF group. Serum ACE activity was markedly suppressed for 24 h after administration, and the inhibition was closely related to plasma diacid levels. A significant inverse correlation was observed between creatinine clearance and the AUC for the diacid. These results suggest that benazepril is rapidly bioactivated to diacid and exhibits rapid onset and long-lasting antihypertensive effects. Dosage reduction might be required to minimize unnecessary drug accumulation in patients with severe IRF."} {"id": "PMID:1279279", "title": "Noninvasive estimates of the inodilatory effects of isoprenaline and their inhibition by transdermally delivered mepindolol in healthy men.", "content": "We analyzed the reproducibility and sensitivity of noninvasive estimates of cardiovascular performance (impedance cardiography and systolic time intervals) to detect and describe the inodilatory responses to isoprenaline (ISO) and their attenuation by transdermally applied mepindolol. The responses to 5-min intravenous (i.v.) infusions of 1 microgram/min ISO in 9 young male healthy volunteers were evaluated repeatedly before and at the end of chronic treatments with daily applied TSD skin patches for transdermal drug delivery with either mepindolol or placebo (double-blind randomized cross-over design). ISO caused a clear increase in mean heart rate (HR), systolic blood pressure (SBP), maximum velocity of impedance changes, estimated stroke volume (SV), and the Heather index, and a reduction in diastolic BP (DBP), estimated systemic vascular resistance (SVR), and a shortening of all systolic time intervals (STIs). These responses were effectively blunted at the end of 1-week treatment with mepindolol TSD patches. Despite overall good agreement of the mean baseline data (under placebo), their within-subject reproducibility nevertheless was too weak to guarantee adequate power to detect small changes under active treatment. Reproducibility of the ISO responses was quite poor, although in a method-independent way. The methods used allowed us to describe the cardiac and vascular components of the ISO responses with adequate detail. Transdermally delivered mepindolol was shown to block ISO responses effectively, but the overall variability of the responses was too large to detect slight changes in them, although the methods in themselves did not appear to be the main cause of this lack of sensitivity.", "contents": "Noninvasive estimates of the inodilatory effects of isoprenaline and their inhibition by transdermally delivered mepindolol in healthy men. We analyzed the reproducibility and sensitivity of noninvasive estimates of cardiovascular performance (impedance cardiography and systolic time intervals) to detect and describe the inodilatory responses to isoprenaline (ISO) and their attenuation by transdermally applied mepindolol. The responses to 5-min intravenous (i.v.) infusions of 1 microgram/min ISO in 9 young male healthy volunteers were evaluated repeatedly before and at the end of chronic treatments with daily applied TSD skin patches for transdermal drug delivery with either mepindolol or placebo (double-blind randomized cross-over design). ISO caused a clear increase in mean heart rate (HR), systolic blood pressure (SBP), maximum velocity of impedance changes, estimated stroke volume (SV), and the Heather index, and a reduction in diastolic BP (DBP), estimated systemic vascular resistance (SVR), and a shortening of all systolic time intervals (STIs). These responses were effectively blunted at the end of 1-week treatment with mepindolol TSD patches. Despite overall good agreement of the mean baseline data (under placebo), their within-subject reproducibility nevertheless was too weak to guarantee adequate power to detect small changes under active treatment. Reproducibility of the ISO responses was quite poor, although in a method-independent way. The methods used allowed us to describe the cardiac and vascular components of the ISO responses with adequate detail. Transdermally delivered mepindolol was shown to block ISO responses effectively, but the overall variability of the responses was too large to detect slight changes in them, although the methods in themselves did not appear to be the main cause of this lack of sensitivity."} {"id": "PMID:1279280", "title": "Contrasting cardiovascular responses from intrathecal administration of epinephrine and norepinephrine in conscious rats: role of alpha 1- and alpha 2-adrenoceptors.", "content": "In conscious rats, intrathecal (i.t.) administration of norepinephrine (NE) produced pressor responses, whereas i.t. epinephrine (Epi) caused depressor responses at low doses (0.1-1 microgram) and pressor responses at a higher dose (10 micrograms). Epi administered i.t. produced bradycardia; however, NE caused tachycardia at low doses and bradycardia at high doses. The cardiovascular responses were dissimilar to those observed after intravenous (i.v.) administration of these doses of NE and Epi. When [3H]NE or [3H]Epi (1.0 microgram, 10 mCi) was injected i.t., minimal radioactivity was detected in peripheral blood (PB) samples, indicating that the effects of i.t.-injected catecholamines on blood pressure (BP) and heart rate (HR) are due to stimulation of central spinal adrenoceptors and not to peripheral effects after leakage. Pretreatment with i.t. administration of the alpha 1-antagonist prazosin (1.0 microgram) attenuated pressor responses and tachycardia produced by i.t. NE (1.0 microgram), whereas i.t. pretreatment with the alpha 2-antagonist yohimbine (10 micrograms) counteracted depressor responses and bradycardia produced by i.t. Epi. Therefore, these spinally released catecholamines appear to produce opposite cardiovascular effects whereby sympathetic preganglionic neurons are excited by NE through spinal alpha 1-adrenoceptors and are inhibited by Epi through spinal alpha 2-adrenoceptors.", "contents": "Contrasting cardiovascular responses from intrathecal administration of epinephrine and norepinephrine in conscious rats: role of alpha 1- and alpha 2-adrenoceptors. In conscious rats, intrathecal (i.t.) administration of norepinephrine (NE) produced pressor responses, whereas i.t. epinephrine (Epi) caused depressor responses at low doses (0.1-1 microgram) and pressor responses at a higher dose (10 micrograms). Epi administered i.t. produced bradycardia; however, NE caused tachycardia at low doses and bradycardia at high doses. The cardiovascular responses were dissimilar to those observed after intravenous (i.v.) administration of these doses of NE and Epi. When [3H]NE or [3H]Epi (1.0 microgram, 10 mCi) was injected i.t., minimal radioactivity was detected in peripheral blood (PB) samples, indicating that the effects of i.t.-injected catecholamines on blood pressure (BP) and heart rate (HR) are due to stimulation of central spinal adrenoceptors and not to peripheral effects after leakage. Pretreatment with i.t. administration of the alpha 1-antagonist prazosin (1.0 microgram) attenuated pressor responses and tachycardia produced by i.t. NE (1.0 microgram), whereas i.t. pretreatment with the alpha 2-antagonist yohimbine (10 micrograms) counteracted depressor responses and bradycardia produced by i.t. Epi. Therefore, these spinally released catecholamines appear to produce opposite cardiovascular effects whereby sympathetic preganglionic neurons are excited by NE through spinal alpha 1-adrenoceptors and are inhibited by Epi through spinal alpha 2-adrenoceptors."} {"id": "PMID:1279281", "title": "Electrophysiologic effects and efficacy of cibenzoline in patients with supraventricular tachycardia.", "content": "Electrophysiologic effects of intravenous (i.v.) cibenzoline were evaluated in 18 patients with accessory pathways or dual atrioventricular (AV) nodal pathways (12 men and 6 women with a mean age of 44 +/- 18 years). Twelve patients had accessory AV pathways, including 6 patients with a manifest accessory pathway. Six patients had AV nodal reentrant tachycardia (AVNRT). Electrophysiologic studies were performed before and after cibenzoline (1.4 mg/kg i.v.) infusion for 5 min. Sinus cycle length did not change significantly after cibenzoline administration. Cibenzoline increased both the AH (85 +/- 20 vs. 91 +/- 21 ms, p less than 0.05) and HV intervals (41 +/- 10 ms vs. 53 +/- 11 ms, p less than 0.001). Neither the atrial nor ventricular effective refractory period (ERP) was altered by cibenzoline. Complete block in the accessory pathway occurred antegradely in 4 patients and retrogradely in 1 patient. Cibenzoline prevented induction of AV reentrant tachycardia (AVRT) in 3 of 8 patients with sustained orthodromic AVRT by abolishing retrograde accessory pathway conduction or prolonging the retrograde accessory pathway ERP. Of 5 patients who continued to have inducible AVRT before and after cibenzoline administration, the tachycardia cycle length was increased in 3, mainly due to the increase in retrograde accessory pathway conduction time. Cibenzoline prevented induction of sustained AVNRT in 4 of 5 patients by prolonging the minimum pacing cycle length, maintaining 1:1 ventriculoatrial (VA) conduction through the retrograde fast AVN pathway or shortening the antegrade fast AVN pathway ERP equal to the slow AVN pathway. In one patient who had an uncommon type of AVNRT, sustained tachycardia was induced by cibenzoline.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Electrophysiologic effects and efficacy of cibenzoline in patients with supraventricular tachycardia. Electrophysiologic effects of intravenous (i.v.) cibenzoline were evaluated in 18 patients with accessory pathways or dual atrioventricular (AV) nodal pathways (12 men and 6 women with a mean age of 44 +/- 18 years). Twelve patients had accessory AV pathways, including 6 patients with a manifest accessory pathway. Six patients had AV nodal reentrant tachycardia (AVNRT). Electrophysiologic studies were performed before and after cibenzoline (1.4 mg/kg i.v.) infusion for 5 min. Sinus cycle length did not change significantly after cibenzoline administration. Cibenzoline increased both the AH (85 +/- 20 vs. 91 +/- 21 ms, p less than 0.05) and HV intervals (41 +/- 10 ms vs. 53 +/- 11 ms, p less than 0.001). Neither the atrial nor ventricular effective refractory period (ERP) was altered by cibenzoline. Complete block in the accessory pathway occurred antegradely in 4 patients and retrogradely in 1 patient. Cibenzoline prevented induction of AV reentrant tachycardia (AVRT) in 3 of 8 patients with sustained orthodromic AVRT by abolishing retrograde accessory pathway conduction or prolonging the retrograde accessory pathway ERP. Of 5 patients who continued to have inducible AVRT before and after cibenzoline administration, the tachycardia cycle length was increased in 3, mainly due to the increase in retrograde accessory pathway conduction time. Cibenzoline prevented induction of sustained AVNRT in 4 of 5 patients by prolonging the minimum pacing cycle length, maintaining 1:1 ventriculoatrial (VA) conduction through the retrograde fast AVN pathway or shortening the antegrade fast AVN pathway ERP equal to the slow AVN pathway. In one patient who had an uncommon type of AVNRT, sustained tachycardia was induced by cibenzoline.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279282", "title": "Calcium antagonistic and binding properties of semotiadil (SD-3211), a benzothiazine derivative assessed in cerebral and coronary arteries.", "content": "The present experiments were undertaken to elucidate Ca2+ antagonistic and binding properties of semotiadil and its (S)-(-)-enantiomer (SD-3212) in plausible clinical target tissues such as cerebral and coronary arteries. Semotiadil was about six times more potent than D-cis-diltiazem for Ca2+ antagonistic action, with a long-lasting and wide spectrum of inhibitory effects on contraction of dog cerebral arteries elicited by various spasmogens and mechanical stretch. Semotiadil exhibited a weak, negative, and heterotropic allosteric effect on (+)-[3H]PN 200-110 binding to pig coronary artery membranes: Scatchard analysis of saturation isotherms indicated that semotiadil increased the equilibrium dissociation constant (Kd) of (+)-[3H]PN-200-110 binding without causing a significant change in the maximum binding density (Bmax). Furthermore, semotiadil significantly increased the dissociation rate (k-1) of (+)-[3H]PN 200-110 from the specific binding site. The enhanced binding of (+)-[3H]PN 200-110 to the coronary artery caused by D-cis-diltiazem was attenuated when semotiadil was present, whereas binding inhibited by verapamil was not affected in the presence of semotiadil. The results suggest that semotiadil exerts a potent Ca2+ antagonistic action by binding to a site in the Ca2+ channel distinct from the 1,4-dihydropyridine recognition site and interacts with the 1,4-dihydropyridine binding site in a negative, heterotropic, allosteric manner.", "contents": "Calcium antagonistic and binding properties of semotiadil (SD-3211), a benzothiazine derivative assessed in cerebral and coronary arteries. The present experiments were undertaken to elucidate Ca2+ antagonistic and binding properties of semotiadil and its (S)-(-)-enantiomer (SD-3212) in plausible clinical target tissues such as cerebral and coronary arteries. Semotiadil was about six times more potent than D-cis-diltiazem for Ca2+ antagonistic action, with a long-lasting and wide spectrum of inhibitory effects on contraction of dog cerebral arteries elicited by various spasmogens and mechanical stretch. Semotiadil exhibited a weak, negative, and heterotropic allosteric effect on (+)-[3H]PN 200-110 binding to pig coronary artery membranes: Scatchard analysis of saturation isotherms indicated that semotiadil increased the equilibrium dissociation constant (Kd) of (+)-[3H]PN-200-110 binding without causing a significant change in the maximum binding density (Bmax). Furthermore, semotiadil significantly increased the dissociation rate (k-1) of (+)-[3H]PN 200-110 from the specific binding site. The enhanced binding of (+)-[3H]PN 200-110 to the coronary artery caused by D-cis-diltiazem was attenuated when semotiadil was present, whereas binding inhibited by verapamil was not affected in the presence of semotiadil. The results suggest that semotiadil exerts a potent Ca2+ antagonistic action by binding to a site in the Ca2+ channel distinct from the 1,4-dihydropyridine recognition site and interacts with the 1,4-dihydropyridine binding site in a negative, heterotropic, allosteric manner."} {"id": "PMID:1279283", "title": "Release of multiple endothelium-derived relaxing factors from porcine coronary arteries.", "content": "Using a chemiluminescence method in the present study, we measured nitric oxide and one-electron oxidation products of nitric oxide (NOX) released from porcine coronary artery segments in response to bradykinin, ADP, and the calcium ionophore A23187. Total NOX was compared with the bioactivity of endothelium-derived relaxing factors (EDRF) by a biodetector ring preparation before and after inhibition of L-arginine-dependent nitric oxide synthesis and in the presence of indomethacin. Under basal conditions, arterial segments released NOX and relaxed biodetector rings. Bradykinin, ADP, and A23187 elicited vasorelaxation greater than that observed basally; A23187, but not bradykinin or ADP, caused additional release of NOX greater than that measured basally. Hemoglobin completely reversed vasorelaxation elicited by all three agonists. We compared the amount of nitric oxide released under basal conditions and after stimulation with bradykinin, ADP, and A23187 with the amount of authentic nitric oxide necessary to elicit a bioequivalent response. Authentic nitric oxide did not account for the observed bioactivity as compared with the amount of nitric oxide actually measured in arterial segment effluent. To investigate whether a second non-nitric oxide-containing compound was responsible for the increased bioactivity and the discrepancy between the bioactivity and quantity of nitric oxide measured, we exposed arterial segments to omega-nitro-L-arginine methyl ester to inhibit L-arginine-dependent synthesis of nitroso compounds. The drug completely abolished the nitric oxide signal derived from both basally released and A23187-stimulated relaxing factor and completely reversed vasorelaxation. In contrast, omega-nitro-L-arginine methyl ester only partially reversed bradykinin-stimulated vasorelaxation.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Release of multiple endothelium-derived relaxing factors from porcine coronary arteries. Using a chemiluminescence method in the present study, we measured nitric oxide and one-electron oxidation products of nitric oxide (NOX) released from porcine coronary artery segments in response to bradykinin, ADP, and the calcium ionophore A23187. Total NOX was compared with the bioactivity of endothelium-derived relaxing factors (EDRF) by a biodetector ring preparation before and after inhibition of L-arginine-dependent nitric oxide synthesis and in the presence of indomethacin. Under basal conditions, arterial segments released NOX and relaxed biodetector rings. Bradykinin, ADP, and A23187 elicited vasorelaxation greater than that observed basally; A23187, but not bradykinin or ADP, caused additional release of NOX greater than that measured basally. Hemoglobin completely reversed vasorelaxation elicited by all three agonists. We compared the amount of nitric oxide released under basal conditions and after stimulation with bradykinin, ADP, and A23187 with the amount of authentic nitric oxide necessary to elicit a bioequivalent response. Authentic nitric oxide did not account for the observed bioactivity as compared with the amount of nitric oxide actually measured in arterial segment effluent. To investigate whether a second non-nitric oxide-containing compound was responsible for the increased bioactivity and the discrepancy between the bioactivity and quantity of nitric oxide measured, we exposed arterial segments to omega-nitro-L-arginine methyl ester to inhibit L-arginine-dependent synthesis of nitroso compounds. The drug completely abolished the nitric oxide signal derived from both basally released and A23187-stimulated relaxing factor and completely reversed vasorelaxation. In contrast, omega-nitro-L-arginine methyl ester only partially reversed bradykinin-stimulated vasorelaxation.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279284", "title": "Role of lipoxygenase and cytochrome P-450 in production of endothelium-derived relaxing factors in canine femoral veins.", "content": "We wished to determine whether the metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, is involved in production of endothelium-derived relaxing factor(s) (EDRFs) in canine femoral veins. Veins were removed from anesthetized dogs and cut into rings. Endothelium was deliberately removed from some rings. In separate sets of experiments, rings were incubated with either AA861 (10(-5) M) or TMK777 (10(-6) M), inhibitors of 5-lipoxygenase, nordihydroguaiaretic acid (NDGA 3 x 10(-6) M), an inhibitor of lipoxygenase or proadifen (SKF 525A, 10(-6) M), an inhibitor of cytochrome P-450. In addition, some rings were incubated with a combination of indomethacin (10(-5) M) and NG-monomethyl-L-arginine (L-NMMA 10(-4) M) or, where appropriate, a solvent control. Concentration-response curves were obtained for acetylcholine, adenosine diphosphate, thrombin, A23187, and nitric oxide in rings contracted with a submaximal concentration of prostaglandin F2 alpha. AA861 and TMK777 did not alter endothelium-dependent relaxations to the agonists, whether with or without indomethacin and L-NMMA. However, indomethacin plus L-NMMA reduced endothelium-dependent relaxations to thrombin. These results suggest that metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, does not produce an EDRF in veins. However, thrombin receptor-activated relaxations are mediated in part by products of the cyclooxygenase pathway and nitric oxide.", "contents": "Role of lipoxygenase and cytochrome P-450 in production of endothelium-derived relaxing factors in canine femoral veins. We wished to determine whether the metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, is involved in production of endothelium-derived relaxing factor(s) (EDRFs) in canine femoral veins. Veins were removed from anesthetized dogs and cut into rings. Endothelium was deliberately removed from some rings. In separate sets of experiments, rings were incubated with either AA861 (10(-5) M) or TMK777 (10(-6) M), inhibitors of 5-lipoxygenase, nordihydroguaiaretic acid (NDGA 3 x 10(-6) M), an inhibitor of lipoxygenase or proadifen (SKF 525A, 10(-6) M), an inhibitor of cytochrome P-450. In addition, some rings were incubated with a combination of indomethacin (10(-5) M) and NG-monomethyl-L-arginine (L-NMMA 10(-4) M) or, where appropriate, a solvent control. Concentration-response curves were obtained for acetylcholine, adenosine diphosphate, thrombin, A23187, and nitric oxide in rings contracted with a submaximal concentration of prostaglandin F2 alpha. AA861 and TMK777 did not alter endothelium-dependent relaxations to the agonists, whether with or without indomethacin and L-NMMA. However, indomethacin plus L-NMMA reduced endothelium-dependent relaxations to thrombin. These results suggest that metabolism of arachidonic acid, through lipoxygenase and cytochrome P-450 pathways, does not produce an EDRF in veins. However, thrombin receptor-activated relaxations are mediated in part by products of the cyclooxygenase pathway and nitric oxide."} {"id": "PMID:1279285", "title": "OPC-13340, a new dihydropyridine calcium channel blocker attenuates rapid vascular smooth muscle cell growth in spontaneously hypertensive rats.", "content": "We investigated the mechanism of the antimitotic effects of calcium channel blockers in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). VSMC from SHR exhibited rapid proliferation through a quick transition from the G0/G1 to the DNA synthetic (S) phase and from the S to the G2/mitotic (M) phase, whereas the DNA synthetic rate itself was equal to that of Wistar-Kyoto rats (WKY). OPC-13340, a new dihydropyridine calcium channel blocker, dose-dependently decreased incorporation of [3H]thymidine into the DNA fragments in randomly cycling VSMC in SHR. Cell cycle analysis showed that the rapid transition from the S to the G2/M period was restored by OPC-13340 to the control level in WKY, whereas the quick transition from G0/G1 to S was unaffected. This antimitotic effect of OPC-13340 was reflected by attenuation of enhanced cellular protein synthesis during the G2/M period. Protein synthesis in the G0/G1 period was not influenced by OPC-13340. Thus, these data indicate that the calcium channel blocker OPC-13340 mitigates the enhanced proliferation observed in randomly cycling VSMC from SHR and that this effect is primarily due to normalization of the premature mitosis during the G2/M period.", "contents": "OPC-13340, a new dihydropyridine calcium channel blocker attenuates rapid vascular smooth muscle cell growth in spontaneously hypertensive rats. We investigated the mechanism of the antimitotic effects of calcium channel blockers in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). VSMC from SHR exhibited rapid proliferation through a quick transition from the G0/G1 to the DNA synthetic (S) phase and from the S to the G2/mitotic (M) phase, whereas the DNA synthetic rate itself was equal to that of Wistar-Kyoto rats (WKY). OPC-13340, a new dihydropyridine calcium channel blocker, dose-dependently decreased incorporation of [3H]thymidine into the DNA fragments in randomly cycling VSMC in SHR. Cell cycle analysis showed that the rapid transition from the S to the G2/M period was restored by OPC-13340 to the control level in WKY, whereas the quick transition from G0/G1 to S was unaffected. This antimitotic effect of OPC-13340 was reflected by attenuation of enhanced cellular protein synthesis during the G2/M period. Protein synthesis in the G0/G1 period was not influenced by OPC-13340. Thus, these data indicate that the calcium channel blocker OPC-13340 mitigates the enhanced proliferation observed in randomly cycling VSMC from SHR and that this effect is primarily due to normalization of the premature mitosis during the G2/M period."} {"id": "PMID:1279286", "title": "Effect of amlodipine pretreatment on ischaemia-reperfusion-induced increase in cardiac endothelin-1 binding site density.", "content": "Endothelin-1 (ET-1) may be implicated in the pathophysiology of myocardial ischaemia. To determine whether the long-acting calcium antagonist amlodipine attenuates the ischaemia- and reperfusion-induced increase in cardiac ET-1 binding sites, hearts from rats pretreated with amlodipine (0.25 or 0.5 mg/kg) 2 or 5 h before they were killed were made ischaemic for 20 or 40 min, reperfused, and subfractionated. Twenty- and 40-min ischaemia caused a time-dependent increase in ET-1 binding site density (Bmax) identified with [125I]ET-1. Amlodipine pretreatment attenuated this increase in a time- and dose-dependent manner. 0.25 and 0.5 mg/kg amlodipine also suppressed the reperfusion-induced increase in [125I]ET-1 binding site density, even when the 0.5-mg/kg pretreatment series reperfusion was administered after 40-min ischaemia.", "contents": "Effect of amlodipine pretreatment on ischaemia-reperfusion-induced increase in cardiac endothelin-1 binding site density. Endothelin-1 (ET-1) may be implicated in the pathophysiology of myocardial ischaemia. To determine whether the long-acting calcium antagonist amlodipine attenuates the ischaemia- and reperfusion-induced increase in cardiac ET-1 binding sites, hearts from rats pretreated with amlodipine (0.25 or 0.5 mg/kg) 2 or 5 h before they were killed were made ischaemic for 20 or 40 min, reperfused, and subfractionated. Twenty- and 40-min ischaemia caused a time-dependent increase in ET-1 binding site density (Bmax) identified with [125I]ET-1. Amlodipine pretreatment attenuated this increase in a time- and dose-dependent manner. 0.25 and 0.5 mg/kg amlodipine also suppressed the reperfusion-induced increase in [125I]ET-1 binding site density, even when the 0.5-mg/kg pretreatment series reperfusion was administered after 40-min ischaemia."} {"id": "PMID:1279287", "title": "Effects of R 56865 and phenytoin on mechanical, biochemical, and morphologic changes during ouabain intoxication in isolated perfused rabbit heart.", "content": "The Na+/Ca2+ overload inhibitor R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl)-N-methyl-2- benzothiazolamine) has been reported to prevent or attenuate ischemia- as well as ouabain-induced cellular sodium and calcium load. We investigated the potency of this compound in preventing mechanical, biochemical, and ultrastructural consequences of ouabain (OUA) intoxication in isolated rabbit heart. The protective effect of the digitalis antidote phenytoin (PHT) on the consequences of ouabain intoxication was examined for comparison. In isolated perfused rabbit heart, OUA (0.4 microM) caused an increase in left ventricular end-diastolic pressure (LVEDP) that was accompanied by depletion of high-energy phosphates (80% less than in control), accumulation of tissue lactate (12-fold) and damage of contractile elements and mitochondria. Accumulation of lactate was associated with a decrease in oxygen consumption by the isolated perfused heart. R 56865 (1.0 microM) and phenytoin (60 microM) prevented increase in LVEDP, breakdown of the energy-rich phosphates creatine phosphate (CrP) and ATP, accumulation of lactate, and morphologic changes induced by OUA. The above-mentioned toxic effects of OUA are interpreted as consequences of mitochondrial failure finally leading to breakdown of the oxidative phosphorylation. Thus, we conclude that the protective action of both compounds, R56865 and PHT, may be attributed to prevention or attenuation of mitochondrial failure due to OUA-induced disturbance of ion homeostasis.", "contents": "Effects of R 56865 and phenytoin on mechanical, biochemical, and morphologic changes during ouabain intoxication in isolated perfused rabbit heart. The Na+/Ca2+ overload inhibitor R 56865 (N-[1-[4-(4-fluorophenoxy)-butyl]-4-piperidinyl)-N-methyl-2- benzothiazolamine) has been reported to prevent or attenuate ischemia- as well as ouabain-induced cellular sodium and calcium load. We investigated the potency of this compound in preventing mechanical, biochemical, and ultrastructural consequences of ouabain (OUA) intoxication in isolated rabbit heart. The protective effect of the digitalis antidote phenytoin (PHT) on the consequences of ouabain intoxication was examined for comparison. In isolated perfused rabbit heart, OUA (0.4 microM) caused an increase in left ventricular end-diastolic pressure (LVEDP) that was accompanied by depletion of high-energy phosphates (80% less than in control), accumulation of tissue lactate (12-fold) and damage of contractile elements and mitochondria. Accumulation of lactate was associated with a decrease in oxygen consumption by the isolated perfused heart. R 56865 (1.0 microM) and phenytoin (60 microM) prevented increase in LVEDP, breakdown of the energy-rich phosphates creatine phosphate (CrP) and ATP, accumulation of lactate, and morphologic changes induced by OUA. The above-mentioned toxic effects of OUA are interpreted as consequences of mitochondrial failure finally leading to breakdown of the oxidative phosphorylation. Thus, we conclude that the protective action of both compounds, R56865 and PHT, may be attributed to prevention or attenuation of mitochondrial failure due to OUA-induced disturbance of ion homeostasis."} {"id": "PMID:1279288", "title": "Placebo-controlled trial of doxazosin in management of patients with hypertension and hypercholesterolaemia.", "content": "The blood pressure (BP)- and lipid-lowering activities of the alpha 1-antagonist, doxazosin, were investigated in hypertensive, hypercholesterolaemic patients. Thirty-one patients satisfactorily completed the study, and there was no significant difference between doxazosin and placebo in terms of reported adverse events. After 3-month treatment, BP was significantly reduced by doxazosin by 24/14 mm Hg supine and by 33/22 mm Hg erect as compared with corresponding reductions of 2/9 and 2/2 mm Hg with placebo. There were concomitant improvements in the plasma lipid profile with, in particular, significant net reductions of 30% for triglycerides and 20% for apoprotein B. There was no adverse effect on glucose metabolism. The principal aim of this study was assessment of the clinical utility and acceptability of doxazosin in a heterogeneous population of patients with several cardiovascular risk factors. The results confirm that doxazosin is an effective antihypertensive agent that has modest additional beneficial effects on the plasma lipid profile.", "contents": "Placebo-controlled trial of doxazosin in management of patients with hypertension and hypercholesterolaemia. The blood pressure (BP)- and lipid-lowering activities of the alpha 1-antagonist, doxazosin, were investigated in hypertensive, hypercholesterolaemic patients. Thirty-one patients satisfactorily completed the study, and there was no significant difference between doxazosin and placebo in terms of reported adverse events. After 3-month treatment, BP was significantly reduced by doxazosin by 24/14 mm Hg supine and by 33/22 mm Hg erect as compared with corresponding reductions of 2/9 and 2/2 mm Hg with placebo. There were concomitant improvements in the plasma lipid profile with, in particular, significant net reductions of 30% for triglycerides and 20% for apoprotein B. There was no adverse effect on glucose metabolism. The principal aim of this study was assessment of the clinical utility and acceptability of doxazosin in a heterogeneous population of patients with several cardiovascular risk factors. The results confirm that doxazosin is an effective antihypertensive agent that has modest additional beneficial effects on the plasma lipid profile."} {"id": "PMID:1279289", "title": "Terbutaline-induced desensitization of beta 2-adrenoceptor in vivo function in humans: attenuation by ketotifen.", "content": "Use of beta-adrenoceptor agonists in long-term treatment of patients with chronic asthma bronchiale or heart failure is of limited value because beta-adrenoceptor desensitization develops. The antiallergic drug ketotifen prevents beta-adrenoceptor agonist-induced desensitization of rat and human pulmonary and lymphocyte beta 2-adrenoceptors. In 10 healthy volunteers in a double-blind, placebo-controlled study, we investigated whether ketotifen also prevents beta-adrenoceptor agonist-induced desensitization of beta 1- and/or beta 2-adrenoceptor-mediated physiologic in vivo effects. beta 1-Adrenoceptor-mediated effects were isoprenaline (ISO) infusion-induced increase in systolic blood pressure (SBP) and bicycle exercise-induced increase in heart rate (HR); beta 2-adrenoceptor-mediated effects were ISO infusion-induced increase in plasma norepinephrine (NE) and decrease in diastolic blood pressure (DBP); ISO infusion-induced increase in HR was assessed as mixed beta 1- and beta 2-adrenoceptor-mediated effect. These parameters were assessed before and after a 14-day treatment with the beta 2-adrenoceptor agonist terbutaline (5 mg three times daily) with or without simultaneous administration of ketotifen (1 mg twice daily). Terbutaline desensitized all in vivo effects involving beta 2-adrenoceptors (ISO-induced decrease in DBP and increase in plasma NE and, to a minor extent, the mixed beta 1- and beta 2-adrenoceptor-mediated increase in HR), but did not affect beta 1-adrenoceptor-mediated in vivo effects; concomitant treatment of the volunteers with ketotifen markedly blunted terbutaline-induced desensitization of beta 2-adrenoceptor in vivo function. We conclude that ketotifen prevents, or at least attenuates, beta-adrenoceptor agonist-induced desensitization of beta 2-adrenoceptor in vivo function.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Terbutaline-induced desensitization of beta 2-adrenoceptor in vivo function in humans: attenuation by ketotifen. Use of beta-adrenoceptor agonists in long-term treatment of patients with chronic asthma bronchiale or heart failure is of limited value because beta-adrenoceptor desensitization develops. The antiallergic drug ketotifen prevents beta-adrenoceptor agonist-induced desensitization of rat and human pulmonary and lymphocyte beta 2-adrenoceptors. In 10 healthy volunteers in a double-blind, placebo-controlled study, we investigated whether ketotifen also prevents beta-adrenoceptor agonist-induced desensitization of beta 1- and/or beta 2-adrenoceptor-mediated physiologic in vivo effects. beta 1-Adrenoceptor-mediated effects were isoprenaline (ISO) infusion-induced increase in systolic blood pressure (SBP) and bicycle exercise-induced increase in heart rate (HR); beta 2-adrenoceptor-mediated effects were ISO infusion-induced increase in plasma norepinephrine (NE) and decrease in diastolic blood pressure (DBP); ISO infusion-induced increase in HR was assessed as mixed beta 1- and beta 2-adrenoceptor-mediated effect. These parameters were assessed before and after a 14-day treatment with the beta 2-adrenoceptor agonist terbutaline (5 mg three times daily) with or without simultaneous administration of ketotifen (1 mg twice daily). Terbutaline desensitized all in vivo effects involving beta 2-adrenoceptors (ISO-induced decrease in DBP and increase in plasma NE and, to a minor extent, the mixed beta 1- and beta 2-adrenoceptor-mediated increase in HR), but did not affect beta 1-adrenoceptor-mediated in vivo effects; concomitant treatment of the volunteers with ketotifen markedly blunted terbutaline-induced desensitization of beta 2-adrenoceptor in vivo function. We conclude that ketotifen prevents, or at least attenuates, beta-adrenoceptor agonist-induced desensitization of beta 2-adrenoceptor in vivo function.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279290", "title": "Alpha-adrenoceptor blockade in patients with mild to moderate hypertension: long-term renal effects of doxazosin.", "content": "Using constant infusion technique and a water-loading procedure, we investigated renal hemodynamic and excretional variables in 15 essential hypertensive patients [diastolic blood pressure (DBP) 102 +/- 10 mm Hg] after 3 weeks of placebo and after 16 weeks of treatment with a postjunctional alpha 1-adrenoceptor-antagonist, doxazosin (1-16 mg) once daily. A minor decrease in supine DBP (p less than 0.05) but no significant changes in systolic BP (SBP) and heart rate (HR) were observed. No significant changes were noted in glomerular filtration rate (GFR), renal plasma flow (RPF), and renal vascular resistance (RVR). The mean renal excretion rate of sodium, potassium, uric acid, and albumin for the entire group was unaffected by the treatment, but the individual changes in sodium clearance correlated significantly with changes in mean BP (r = 0.64, n = 15, p less than 0.05). Six patients showed an increase in sodium excretion after treatment, whereas nine showed a decrease. No decrease in mean body weight was noted, but the BP reduction after 5 months of treatment correlated significantly with the changes in body weight (r = 0.62, n = 15, p less than 0.01). The results indicate that long-term treatment with doxazosin had no deleterious effect on renal function, but the effects on BP were rather modest. The individual BP response is probably determined by the degree of fluid retention even if an intact pressure-natriuresis relationship could still be demonstrated during chronic therapy.", "contents": "Alpha-adrenoceptor blockade in patients with mild to moderate hypertension: long-term renal effects of doxazosin. Using constant infusion technique and a water-loading procedure, we investigated renal hemodynamic and excretional variables in 15 essential hypertensive patients [diastolic blood pressure (DBP) 102 +/- 10 mm Hg] after 3 weeks of placebo and after 16 weeks of treatment with a postjunctional alpha 1-adrenoceptor-antagonist, doxazosin (1-16 mg) once daily. A minor decrease in supine DBP (p less than 0.05) but no significant changes in systolic BP (SBP) and heart rate (HR) were observed. No significant changes were noted in glomerular filtration rate (GFR), renal plasma flow (RPF), and renal vascular resistance (RVR). The mean renal excretion rate of sodium, potassium, uric acid, and albumin for the entire group was unaffected by the treatment, but the individual changes in sodium clearance correlated significantly with changes in mean BP (r = 0.64, n = 15, p less than 0.05). Six patients showed an increase in sodium excretion after treatment, whereas nine showed a decrease. No decrease in mean body weight was noted, but the BP reduction after 5 months of treatment correlated significantly with the changes in body weight (r = 0.62, n = 15, p less than 0.01). The results indicate that long-term treatment with doxazosin had no deleterious effect on renal function, but the effects on BP were rather modest. The individual BP response is probably determined by the degree of fluid retention even if an intact pressure-natriuresis relationship could still be demonstrated during chronic therapy."} {"id": "PMID:1279291", "title": "Mechanism of halothane attenuation of isometric tension induced by serotonin in isolated canine coronary artery rings.", "content": "We explored the mechanism of halothane's interaction with the serotoninergic contractile response of isolated canine coronary artery rings. The serotoninergic contractile response of both intact and denuded rings was measured with and without halothane. In some experiments, rings were pretreated with methiothepin, a 5-HT1 and 5-HT2 antagonist, or ketanserin, a 5-HT2 antagonist. The contractile responses to 5-carboxamidotryptamine (5-CT) and alpha-methylserotonin, a 5-HT1 and a 5-HT2 receptor agonist, respectively, were measured with and without halothane. Finally, the response to prostaglandin F2-alpha, another spasm mediator, was also measured with and without halothane. Halothane attenuated the coronary artery response to serotonin (5-hydroxytryptamine, 5-HT), and specific 5-HT1 and 5-HT2 agonists, and prostaglandin F2 alpha (PGF2 alpha). Its inhibitory effect on the serotoninergic response was abolished in vessels pretreated with either 5-HT1 or 5-HT2 blockers. These data suggest that halothane is not a direct smooth muscle depressant, that it is not a specific 5-HT1- or 5-HT2-subtype antagonist in canine coronary arteries, and that it might interfere with intracellular pathways activated by agonist-receptor interactions.", "contents": "Mechanism of halothane attenuation of isometric tension induced by serotonin in isolated canine coronary artery rings. We explored the mechanism of halothane's interaction with the serotoninergic contractile response of isolated canine coronary artery rings. The serotoninergic contractile response of both intact and denuded rings was measured with and without halothane. In some experiments, rings were pretreated with methiothepin, a 5-HT1 and 5-HT2 antagonist, or ketanserin, a 5-HT2 antagonist. The contractile responses to 5-carboxamidotryptamine (5-CT) and alpha-methylserotonin, a 5-HT1 and a 5-HT2 receptor agonist, respectively, were measured with and without halothane. Finally, the response to prostaglandin F2-alpha, another spasm mediator, was also measured with and without halothane. Halothane attenuated the coronary artery response to serotonin (5-hydroxytryptamine, 5-HT), and specific 5-HT1 and 5-HT2 agonists, and prostaglandin F2 alpha (PGF2 alpha). Its inhibitory effect on the serotoninergic response was abolished in vessels pretreated with either 5-HT1 or 5-HT2 blockers. These data suggest that halothane is not a direct smooth muscle depressant, that it is not a specific 5-HT1- or 5-HT2-subtype antagonist in canine coronary arteries, and that it might interfere with intracellular pathways activated by agonist-receptor interactions."} {"id": "PMID:1279292", "title": "Steady-state pharmacokinetics and pharmacodynamics of cilazapril in the presence and absence of cyclopenthiazide.", "content": "Twenty-two patients with essential hypertension received a single dose of 2.5 mg cilazapril and were then randomised into a double-blind parallel group study to receive either placebo, 1.25 mg cilazapril + 0.5 mg cyclopenthiazide (CPTZ), 2.5 mg cilazapril + 0.5 mg CPTZ, or 2.5 mg cilazapril alone for 1 month. After oral administration of a single dose of 2.5 mg cilazapril, the active diacid cilazaprilat appeared rapidly in the plasma (Tmax 2.0 +/- 0.2 h). With the radioinhibitor assay used in this study, a single elimination phase of cilazaprilat was evident, with a half-life (t1/2) of 2-3 h. At steady state, the pharmacokinetics of cilazaprilat were similar to single-dose administration and were not altered by CPTZ. The Cmax and area under the curve (AUC) of cilazaprilat were directly proportional to dose. Cilazapril administration in the dose range of 1.25-2.5 mg produced a dose-proportional inhibition of angiotensin-converting enzyme (ACE) activity that was maximum 2 h after drug administration. The degree of ACE inhibition correlated with the plasma concentration-time profile of cilazaprilat and the maximum decrease in blood pressure (BP). The EC50 for ACE inhibition by cilazaprilat was 7.7 ng/ml after acute treatment and was not significantly altered during chronic administration or by concomitant administration of CPTZ. There was no evidence of a dose-related antihypertensive effect of cilazapril at steady state and, with the small numbers of subjects used in this study, there was no evidence of 24-h BP control with monotherapy.", "contents": "Steady-state pharmacokinetics and pharmacodynamics of cilazapril in the presence and absence of cyclopenthiazide. Twenty-two patients with essential hypertension received a single dose of 2.5 mg cilazapril and were then randomised into a double-blind parallel group study to receive either placebo, 1.25 mg cilazapril + 0.5 mg cyclopenthiazide (CPTZ), 2.5 mg cilazapril + 0.5 mg CPTZ, or 2.5 mg cilazapril alone for 1 month. After oral administration of a single dose of 2.5 mg cilazapril, the active diacid cilazaprilat appeared rapidly in the plasma (Tmax 2.0 +/- 0.2 h). With the radioinhibitor assay used in this study, a single elimination phase of cilazaprilat was evident, with a half-life (t1/2) of 2-3 h. At steady state, the pharmacokinetics of cilazaprilat were similar to single-dose administration and were not altered by CPTZ. The Cmax and area under the curve (AUC) of cilazaprilat were directly proportional to dose. Cilazapril administration in the dose range of 1.25-2.5 mg produced a dose-proportional inhibition of angiotensin-converting enzyme (ACE) activity that was maximum 2 h after drug administration. The degree of ACE inhibition correlated with the plasma concentration-time profile of cilazaprilat and the maximum decrease in blood pressure (BP). The EC50 for ACE inhibition by cilazaprilat was 7.7 ng/ml after acute treatment and was not significantly altered during chronic administration or by concomitant administration of CPTZ. There was no evidence of a dose-related antihypertensive effect of cilazapril at steady state and, with the small numbers of subjects used in this study, there was no evidence of 24-h BP control with monotherapy."} {"id": "PMID:1279293", "title": "Electrophysiologic and hemodynamic effects of H 234/09 (almokalant), quinidine, and (+)-sotalol in the anesthetized dog.", "content": "The electrophysiologic and hemodynamic effects of H 234/09 (Almokalant), a novel class II antiarrhythmic agent, were studied in the anesthetized dog. H 234/09 (1.0 mumol/kg i.v.) significantly prolonged the atrial and ventricular effective refractory periods, the ventricular monophasic action potential duration, and the paced QT interval. At this dose, atrial, ventricular, and atrioventricular conduction was not affected, aortic blood pressure was not changed, and contractile force was transiently increased. The effects on cardiac repolarization and refractoriness induced by H 234/09 were both larger and more long lasting than the effects observed after quinidine (11.8 mumol/kg) and (+)-sotalol (9.7 mumol/kg). However, both quinidine and (+)-sotalol significantly reduced the aortic blood pressure and (+)-sotalol also decreased cardiac contractility. The effect of H 234/09 on atrial refractoriness was very little influenced by the paced heart rate and was twice as large as the corresponding effect in the ventricle. In conclusion, H 234/09 has electrophysiological properties suggestive of a class III antiarrhythmic. H 234/09 may have a favorable therapeutic profile compared to both quinidine and (+)-sotalol, especially for the treatment of atrial arrhythmias.", "contents": "Electrophysiologic and hemodynamic effects of H 234/09 (almokalant), quinidine, and (+)-sotalol in the anesthetized dog. The electrophysiologic and hemodynamic effects of H 234/09 (Almokalant), a novel class II antiarrhythmic agent, were studied in the anesthetized dog. H 234/09 (1.0 mumol/kg i.v.) significantly prolonged the atrial and ventricular effective refractory periods, the ventricular monophasic action potential duration, and the paced QT interval. At this dose, atrial, ventricular, and atrioventricular conduction was not affected, aortic blood pressure was not changed, and contractile force was transiently increased. The effects on cardiac repolarization and refractoriness induced by H 234/09 were both larger and more long lasting than the effects observed after quinidine (11.8 mumol/kg) and (+)-sotalol (9.7 mumol/kg). However, both quinidine and (+)-sotalol significantly reduced the aortic blood pressure and (+)-sotalol also decreased cardiac contractility. The effect of H 234/09 on atrial refractoriness was very little influenced by the paced heart rate and was twice as large as the corresponding effect in the ventricle. In conclusion, H 234/09 has electrophysiological properties suggestive of a class III antiarrhythmic. H 234/09 may have a favorable therapeutic profile compared to both quinidine and (+)-sotalol, especially for the treatment of atrial arrhythmias."} {"id": "PMID:1279294", "title": "Neuropeptide Y inhibits relaxation of guinea pig cerebral, coronary, and uterine arteries: blockade by D-myo-inositol-1,2,6-triphosphate.", "content": "Interactions between neuropeptide Y and perivascular vasodilator agents were studied in guinea pig cerebral, coronary, and uterine arteries. In all three types of arteries, vessel segments precontracted with prostaglandin F2 alpha or histamine relaxed concentration dependently upon application of acetylcholine (ACh), substance P (SP), and vasoactive intestinal peptide (VIP). Neuropeptide Y (NPY: 10(-8)-10(-7) M) caused inhibition of relaxations produced by ACh, SP, and VIP in all three types of segments; however, the effective concentration varied between vessel type. Thus, cerebral and uterine arteries were approximately 10 times more sensitive to NPY than the coronary artery. D-myo-inositol-1,2,6-triphosphate (PP56) was a potent inhibitor of the NPY effect in all three vessel types. Thus, NPY, which is colocalized not only with norepinephrine in sympathetic perivascular fibers but also with VIP and ACh in some parasympathetic neurons, can greatly reduce the vasodilatory effect of ACh and VIP, as well as of the sensory peptide SP. This further illustrates the complex interactions NPY has with perivascular neuroeffector mechanisms.", "contents": "Neuropeptide Y inhibits relaxation of guinea pig cerebral, coronary, and uterine arteries: blockade by D-myo-inositol-1,2,6-triphosphate. Interactions between neuropeptide Y and perivascular vasodilator agents were studied in guinea pig cerebral, coronary, and uterine arteries. In all three types of arteries, vessel segments precontracted with prostaglandin F2 alpha or histamine relaxed concentration dependently upon application of acetylcholine (ACh), substance P (SP), and vasoactive intestinal peptide (VIP). Neuropeptide Y (NPY: 10(-8)-10(-7) M) caused inhibition of relaxations produced by ACh, SP, and VIP in all three types of segments; however, the effective concentration varied between vessel type. Thus, cerebral and uterine arteries were approximately 10 times more sensitive to NPY than the coronary artery. D-myo-inositol-1,2,6-triphosphate (PP56) was a potent inhibitor of the NPY effect in all three vessel types. Thus, NPY, which is colocalized not only with norepinephrine in sympathetic perivascular fibers but also with VIP and ACh in some parasympathetic neurons, can greatly reduce the vasodilatory effect of ACh and VIP, as well as of the sensory peptide SP. This further illustrates the complex interactions NPY has with perivascular neuroeffector mechanisms."} {"id": "PMID:1279295", "title": "Dose-response curve of angiographically smooth human epicardial vessel segments to intracoronary injections of isosorbide dinitrate.", "content": "The coronary vasodilator properties of isosorbide dinitrate are well established but the doses generally used (1,000-2,000 micrograms) are still empirical. We studied, with the use of quantitative coronary arteriography (CAESAR System), the response of smooth vessel segments (greater than 1.85 mm diameter), preconstricted with methylergometrine (400 micrograms i.v.), to intracoronary injections of graded doses (5-100 micrograms) of isosorbide dinitrate and the effects of these injections on systemic hemodynamic parameters in 10 patients undergoing diagnostic coronary angiography. Six further patients, in whom the injections of isosorbide dinitrate were replaced by equivalent volumes of normal saline, served as controls. Relative to the diameter 5 min after injection of methylergometrine, the diameter increased by a mean +/- SD of 9 +/- 7, 26 +/- 12, 33 +/- 15, 38 +/- 14, and 39 +/- 16% after injections of 5, 15, 60, 240, and 1,000 micrograms, respectively, of isosorbide dinitrate. After a cumulative dose of 80 micrograms, subsequent doses did not cause further significant increases in diameter. Injection of saline in the control group did not alter the coronary diameter. A significant fall in systolic arterial pressure, compared to the control group, occurred at a cumulative dose of 320 micrograms. The mean arterial pressure and heart rate were unchanged. Significant coronary vasodilation occurs with intracoronary doses of isosorbide much smaller than those currently employed. Cumulative doses of 320 micrograms or more cause systemic hemodynamic changes without producing additional coronary vasodilation. During interventional cardiac procedures, where systemic hypotension is undesirable, the use of smaller doses of intracoronary isosorbide dinitrate than currently employed may be feasible and should be investigated further.", "contents": "Dose-response curve of angiographically smooth human epicardial vessel segments to intracoronary injections of isosorbide dinitrate. The coronary vasodilator properties of isosorbide dinitrate are well established but the doses generally used (1,000-2,000 micrograms) are still empirical. We studied, with the use of quantitative coronary arteriography (CAESAR System), the response of smooth vessel segments (greater than 1.85 mm diameter), preconstricted with methylergometrine (400 micrograms i.v.), to intracoronary injections of graded doses (5-100 micrograms) of isosorbide dinitrate and the effects of these injections on systemic hemodynamic parameters in 10 patients undergoing diagnostic coronary angiography. Six further patients, in whom the injections of isosorbide dinitrate were replaced by equivalent volumes of normal saline, served as controls. Relative to the diameter 5 min after injection of methylergometrine, the diameter increased by a mean +/- SD of 9 +/- 7, 26 +/- 12, 33 +/- 15, 38 +/- 14, and 39 +/- 16% after injections of 5, 15, 60, 240, and 1,000 micrograms, respectively, of isosorbide dinitrate. After a cumulative dose of 80 micrograms, subsequent doses did not cause further significant increases in diameter. Injection of saline in the control group did not alter the coronary diameter. A significant fall in systolic arterial pressure, compared to the control group, occurred at a cumulative dose of 320 micrograms. The mean arterial pressure and heart rate were unchanged. Significant coronary vasodilation occurs with intracoronary doses of isosorbide much smaller than those currently employed. Cumulative doses of 320 micrograms or more cause systemic hemodynamic changes without producing additional coronary vasodilation. During interventional cardiac procedures, where systemic hypotension is undesirable, the use of smaller doses of intracoronary isosorbide dinitrate than currently employed may be feasible and should be investigated further."} {"id": "PMID:1279296", "title": "Positive inotropic effects due to partial agonistic activity of the beta-adrenoceptor antagonist celiprolol following amplification of cAMP formation in failing human myocardium.", "content": "The present study investigated the effects of celiprolol a novel beta 1-antagonist with partial beta 2-agonist activity on the human failing heart. Experiments were performed on isolated electrically driven atrial and ventricular cardiac preparations and in membrane preparations from the left ventricles of nine patients (four with dilated cardiomyopathy; five with ischemic cardiomyopathy) undergoing cardiac transplantation for terminal heart failure. Celiprolol produced a negative inotropic effect in atrial and ventricular heart muscle. However, in the presence of forskolin--which activates the catalyst of the adenylate cyclase-or the cAMP phosphodiesterase inhibitor milrinone, celiprolol produced concentration-dependent positive inotropic effects and positive lusitropic effects. Experiments with the beta 1-and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, suggest that the positive inotropic response is mediated by beta 2-adrenoceptors. In radioligand binding experiments, a selectivity of 15.7 [-Gpp(NH)p] or 23.9 [+Gpp(NH)p] as judged from the Ki values--of binding to beta 2-adrenoceptors was measured in the failing human ventricular myocardium. Competition curves with celiprolol alone and in the presence of the guanine nucleotide Gpp(NH)p revealed no evidence for agonist activity at beta 1- or beta 2-adrenoceptors. It is concluded that amplification of the cAMP response is able to unmask partial agonist activity of celiprolol in the failing human heart at beta 2-adrenoceptors. The inotropic measurements are a more sensitive approach than radioligand binding studies. Whether the pharmacological profile of celiprolol will be useful in conditions like heart failure is questionable with respect to the potential downregulation of beta 2-adrenoceptors by its partial agonist activity.", "contents": "Positive inotropic effects due to partial agonistic activity of the beta-adrenoceptor antagonist celiprolol following amplification of cAMP formation in failing human myocardium. The present study investigated the effects of celiprolol a novel beta 1-antagonist with partial beta 2-agonist activity on the human failing heart. Experiments were performed on isolated electrically driven atrial and ventricular cardiac preparations and in membrane preparations from the left ventricles of nine patients (four with dilated cardiomyopathy; five with ischemic cardiomyopathy) undergoing cardiac transplantation for terminal heart failure. Celiprolol produced a negative inotropic effect in atrial and ventricular heart muscle. However, in the presence of forskolin--which activates the catalyst of the adenylate cyclase-or the cAMP phosphodiesterase inhibitor milrinone, celiprolol produced concentration-dependent positive inotropic effects and positive lusitropic effects. Experiments with the beta 1-and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, suggest that the positive inotropic response is mediated by beta 2-adrenoceptors. In radioligand binding experiments, a selectivity of 15.7 [-Gpp(NH)p] or 23.9 [+Gpp(NH)p] as judged from the Ki values--of binding to beta 2-adrenoceptors was measured in the failing human ventricular myocardium. Competition curves with celiprolol alone and in the presence of the guanine nucleotide Gpp(NH)p revealed no evidence for agonist activity at beta 1- or beta 2-adrenoceptors. It is concluded that amplification of the cAMP response is able to unmask partial agonist activity of celiprolol in the failing human heart at beta 2-adrenoceptors. The inotropic measurements are a more sensitive approach than radioligand binding studies. Whether the pharmacological profile of celiprolol will be useful in conditions like heart failure is questionable with respect to the potential downregulation of beta 2-adrenoceptors by its partial agonist activity."} {"id": "PMID:1279297", "title": "Effect of lisinopril and isosorbide-5-mononitrate on hemodynamics and mortality in rats with permanent coronary artery occlusion.", "content": "We studied the hemodynamic effects of lisinopril and isosorbide-5-mononitrate in rats with permanent coronary occlusion. Rats (n = 35) underwent left coronary occlusion, and ECGs were recorded before and after occlusion. Ventricular arrhythmias were observed in 57% (20 of 35) of animals. Treatment was given immediately after coronary occlusion and for 2 subsequent days. The control group received 100 mg/kg lactose (i.e., 80% vehicle for isosorbide-5-mononitrate). Lisinopril (100 mg/kg body weight) and isosorbide-5-mononitrate (400 mg/kg body weight) reduced systolic blood pressure (SBP) from 134 +/- 9 to 115 +/- 9 mm Hg (p less than 0.05) and from 137 +/- 9 to 126 +/- 9 mm Hg, respectively; the hypotensive effect lasted 2-3 days. No effect on BP was noted in the control group. Overall mortality was 23%; 8 of 35 animals died within 10-15 min of coronary occlusion. Survival after 4 weeks was similar in each group (approximately 80%). Left ventricular pressure (LVP) was measured 4 weeks after coronary artery occlusion and was similar in each group. However, dP/dt was lower in hearts with infarction than in hearts with none (12,608 +/- 906 vs. 8,992 +/- 1,242 mm Hg/s). The extent of the infarction was the same in groups with coronary artery occlusion. Lisinopril is more effective than isosorbide-5-mononitrate in reducing BP after acute myocardial infarction (AMI). Medium-term survival (4 weeks) is not jeopardized by effective treatment with angiotensin-converting enzyme (ACE) inhibitors or long-acting nitrates.", "contents": "Effect of lisinopril and isosorbide-5-mononitrate on hemodynamics and mortality in rats with permanent coronary artery occlusion. We studied the hemodynamic effects of lisinopril and isosorbide-5-mononitrate in rats with permanent coronary occlusion. Rats (n = 35) underwent left coronary occlusion, and ECGs were recorded before and after occlusion. Ventricular arrhythmias were observed in 57% (20 of 35) of animals. Treatment was given immediately after coronary occlusion and for 2 subsequent days. The control group received 100 mg/kg lactose (i.e., 80% vehicle for isosorbide-5-mononitrate). Lisinopril (100 mg/kg body weight) and isosorbide-5-mononitrate (400 mg/kg body weight) reduced systolic blood pressure (SBP) from 134 +/- 9 to 115 +/- 9 mm Hg (p less than 0.05) and from 137 +/- 9 to 126 +/- 9 mm Hg, respectively; the hypotensive effect lasted 2-3 days. No effect on BP was noted in the control group. Overall mortality was 23%; 8 of 35 animals died within 10-15 min of coronary occlusion. Survival after 4 weeks was similar in each group (approximately 80%). Left ventricular pressure (LVP) was measured 4 weeks after coronary artery occlusion and was similar in each group. However, dP/dt was lower in hearts with infarction than in hearts with none (12,608 +/- 906 vs. 8,992 +/- 1,242 mm Hg/s). The extent of the infarction was the same in groups with coronary artery occlusion. Lisinopril is more effective than isosorbide-5-mononitrate in reducing BP after acute myocardial infarction (AMI). Medium-term survival (4 weeks) is not jeopardized by effective treatment with angiotensin-converting enzyme (ACE) inhibitors or long-acting nitrates."} {"id": "PMID:1279298", "title": "The neutral endopeptidase inhibitor, SCH 34826, reduces left ventricular hypertrophy in spontaneously hypertensive rats.", "content": "SCH 34826, i.e., (S)-N-(N-(2,2[(2,2-dimethyl-1,3-dioxolan-4- yl)methoxy]-2-oxo-1-(phenyl-methyl)ethyl)-phenylalanyl)-beta-alanine, is a potent and selective inhibitor of neutral endopeptidase 24.11 (NEP), an enzyme that degrades the atrial natriuretic peptide (ANP). The effects of SCH 34826 on hypertension and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs) were evaluated following 1 month of treatment by measuring the blood pressure, cardiac weight, and left ventricular fibrosis. Adult SHRs were treated with SCH 34826 at 10, 30, or 100 mg/kg given orally twice daily or with vehicle. The systolic blood pressure (SBP) and heart rate (HR) were recorded weekly by the tail-cuff method. Cardiac structural damage was determined by morphometric analysis. Over the dose range examined, the drug produced no significant changes in either blood pressure or heart rate. Despite the lack of antihypertensive activity, SCH 34826 at 100 mg/kg reduced both the cardiac mass (-10%) and the amount of fibrotic tissue present in the left ventricle (-42%). These data indicate that chronic inhibition of NEP by SCH 34826 interacts with mechanisms underlying myocardial hypertrophy and cardiac remodeling.", "contents": "The neutral endopeptidase inhibitor, SCH 34826, reduces left ventricular hypertrophy in spontaneously hypertensive rats. SCH 34826, i.e., (S)-N-(N-(2,2[(2,2-dimethyl-1,3-dioxolan-4- yl)methoxy]-2-oxo-1-(phenyl-methyl)ethyl)-phenylalanyl)-beta-alanine, is a potent and selective inhibitor of neutral endopeptidase 24.11 (NEP), an enzyme that degrades the atrial natriuretic peptide (ANP). The effects of SCH 34826 on hypertension and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHRs) were evaluated following 1 month of treatment by measuring the blood pressure, cardiac weight, and left ventricular fibrosis. Adult SHRs were treated with SCH 34826 at 10, 30, or 100 mg/kg given orally twice daily or with vehicle. The systolic blood pressure (SBP) and heart rate (HR) were recorded weekly by the tail-cuff method. Cardiac structural damage was determined by morphometric analysis. Over the dose range examined, the drug produced no significant changes in either blood pressure or heart rate. Despite the lack of antihypertensive activity, SCH 34826 at 100 mg/kg reduced both the cardiac mass (-10%) and the amount of fibrotic tissue present in the left ventricle (-42%). These data indicate that chronic inhibition of NEP by SCH 34826 interacts with mechanisms underlying myocardial hypertrophy and cardiac remodeling."} {"id": "PMID:1279299", "title": "Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects.", "content": "In a double-blind, placebo-controlled, parallel group study, 24 essential hypertensive subjects were randomised to receive either placebo or 2, 4, or 8 mg perindopril. Perindopril, its deesterified metabolite, perindoprilat, and perindoprilat glucuronide were separated with an ion-exchange resin and determined by a radioimmunoassay (RIA). Pharmacokinetic and pharmacodynamic parameters were estimated for 96 h after the first dose and after 4-week once-daily treatment. Perindopril peak levels were achieved in less than or equal to 2 h after dosing with an elimination t1/2 of 1-2 h. Peak levels of perindoprilat were achieved more slowly, reaching a maximum level 5-8 h after dosing, and had an elimination t1/2 of 40 h. Levels of the perindopril glucuronide peaked approximately 0.5 h later than perindopril, with an elimination t1/2 of approximately 2 h. Perindopril, perindoprilat, and its glucuronide conjugate followed linear kinetics in the dose range of 2-8 mg, and there was no evidence of accumulation with chronic dosing. Perindopril 4 and 8 mg produced significant decreases in predose blood pressure (BP) with chronic dosing, with maximal decreases occurring 5-7 h after dosing. Perindopril also produced a prolonged dose-dependent inhibition of plasma angiotensin-converting enzyme (ACE) activity that was maximum after 4 h and had not fully recovered by 48 h after a single dose.", "contents": "Single-dose and steady-state pharmacokinetics and pharmacodynamics of perindopril in hypertensive subjects. In a double-blind, placebo-controlled, parallel group study, 24 essential hypertensive subjects were randomised to receive either placebo or 2, 4, or 8 mg perindopril. Perindopril, its deesterified metabolite, perindoprilat, and perindoprilat glucuronide were separated with an ion-exchange resin and determined by a radioimmunoassay (RIA). Pharmacokinetic and pharmacodynamic parameters were estimated for 96 h after the first dose and after 4-week once-daily treatment. Perindopril peak levels were achieved in less than or equal to 2 h after dosing with an elimination t1/2 of 1-2 h. Peak levels of perindoprilat were achieved more slowly, reaching a maximum level 5-8 h after dosing, and had an elimination t1/2 of 40 h. Levels of the perindopril glucuronide peaked approximately 0.5 h later than perindopril, with an elimination t1/2 of approximately 2 h. Perindopril, perindoprilat, and its glucuronide conjugate followed linear kinetics in the dose range of 2-8 mg, and there was no evidence of accumulation with chronic dosing. Perindopril 4 and 8 mg produced significant decreases in predose blood pressure (BP) with chronic dosing, with maximal decreases occurring 5-7 h after dosing. Perindopril also produced a prolonged dose-dependent inhibition of plasma angiotensin-converting enzyme (ACE) activity that was maximum after 4 h and had not fully recovered by 48 h after a single dose."} {"id": "PMID:1279301", "title": "The relevance of cellular to clinical electrophysiology in classifying antiarrhythmic actions.", "content": "The division of class I antiarrhythmic agents (sodium-channel blockers) into Ia, Ib, and Ic subgroups was based on clinical observations. Lidocaine, mexiletine, and tocainide (Ib) did not alter the QRS or H-V interval in sinus rhythm, but prolonged effective refractory period (ERP) in spite of some shortening of the J-T interval. Encainide, flecainide, and lorcainide (Ic) widened the QRS and prolonged H-V in sinus rhythm and at low concentration, but had little effect on the ERP or J-T. These clinical findings could be explained by fast onset/offset kinetics of Ib drugs, that when used in high concentrations, blocked most sodium channels during the action potential plateau; therefore, at the beginning of diastole, insufficient drug-free channels were available to support conduction, and the ERP was prolonged. Rapid dissociation of the drugs after repolarization insured that by the end of diastole most channels were again drug free, so that the QRS and H-V were normal. The Ic compounds were more potent, but of slow onset, so that a steady-state block of Na channels was not achieved until after many beats. Offset was also slow, so that a proportion of channels was persistently unavailable, Na current was reduced, and conduction slowed, causing widening of the QRS and lengthening of H-V. Because the remaining drug-free channels were normal, they recovered rapidly from inactivation, and the ERP was not prolonged. By clinical criteria, moricizine also must be classed as Ic, and its offset/onset kinetics are much slower than those of Ib drugs.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "The relevance of cellular to clinical electrophysiology in classifying antiarrhythmic actions. The division of class I antiarrhythmic agents (sodium-channel blockers) into Ia, Ib, and Ic subgroups was based on clinical observations. Lidocaine, mexiletine, and tocainide (Ib) did not alter the QRS or H-V interval in sinus rhythm, but prolonged effective refractory period (ERP) in spite of some shortening of the J-T interval. Encainide, flecainide, and lorcainide (Ic) widened the QRS and prolonged H-V in sinus rhythm and at low concentration, but had little effect on the ERP or J-T. These clinical findings could be explained by fast onset/offset kinetics of Ib drugs, that when used in high concentrations, blocked most sodium channels during the action potential plateau; therefore, at the beginning of diastole, insufficient drug-free channels were available to support conduction, and the ERP was prolonged. Rapid dissociation of the drugs after repolarization insured that by the end of diastole most channels were again drug free, so that the QRS and H-V were normal. The Ic compounds were more potent, but of slow onset, so that a steady-state block of Na channels was not achieved until after many beats. Offset was also slow, so that a proportion of channels was persistently unavailable, Na current was reduced, and conduction slowed, causing widening of the QRS and lengthening of H-V. Because the remaining drug-free channels were normal, they recovered rapidly from inactivation, and the ERP was not prolonged. By clinical criteria, moricizine also must be classed as Ic, and its offset/onset kinetics are much slower than those of Ib drugs.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279302", "title": "RP 58866 and its active enantiomer RP 62719 (terikalant): blockers of the inward rectifier K+ current acting as pure class III antiarrhythmic agents.", "content": "The present article presents an overview of the pharmacologic profile of the benzopyran derivative RP 58866, a racemic mixture, and of RP 62719 (terikalant), its active enantiomer. In normal cardiac tissues studied in vitro, both drugs dose-dependently prolonged the atrial and ventricular action potential but affected neither the upstroke of the action potential nor the diastolic potential. Patch-clamp experiments demonstrated that the prolongation of the action potential induced by the drugs is due to a specific blockade of the inward rectifier K+ current. In vivo, intravenous administration to anesthetized dogs of low doses of RP 62719 consistently induced bradycardia and prolonged the atrial, nodal, and ventricular refractory periods, but did not affect the conduction velocity. Because of these properties, RP 58866 and RP 62719 exert potent antiarrhythmic and antifibrillatory actions both at the atrial and ventricular levels in various experimental models of arrhythmia. Our results demonstrate that RP 58866 and RP 62719 are K(+)-channel blockers acting as pure class III antiarrhythmic drugs.", "contents": "RP 58866 and its active enantiomer RP 62719 (terikalant): blockers of the inward rectifier K+ current acting as pure class III antiarrhythmic agents. The present article presents an overview of the pharmacologic profile of the benzopyran derivative RP 58866, a racemic mixture, and of RP 62719 (terikalant), its active enantiomer. In normal cardiac tissues studied in vitro, both drugs dose-dependently prolonged the atrial and ventricular action potential but affected neither the upstroke of the action potential nor the diastolic potential. Patch-clamp experiments demonstrated that the prolongation of the action potential induced by the drugs is due to a specific blockade of the inward rectifier K+ current. In vivo, intravenous administration to anesthetized dogs of low doses of RP 62719 consistently induced bradycardia and prolonged the atrial, nodal, and ventricular refractory periods, but did not affect the conduction velocity. Because of these properties, RP 58866 and RP 62719 exert potent antiarrhythmic and antifibrillatory actions both at the atrial and ventricular levels in various experimental models of arrhythmia. Our results demonstrate that RP 58866 and RP 62719 are K(+)-channel blockers acting as pure class III antiarrhythmic drugs."} {"id": "PMID:1279303", "title": "Statistical problems in the design of antiarrhythmic drug trials.", "content": "Although many aspects of design, monitoring, and analysis in trials of antiarrhythmic drugs are similar to those of other intervention studies, several features are different. These include decisions on how to identify the subjects, timing of the intervention with respect to the disease process, time of randomization, methods for measurement of outcome, and interim monitoring for harm or benefit. The resolution of these issues depends almost entirely on the specification of the question of interest.", "contents": "Statistical problems in the design of antiarrhythmic drug trials. Although many aspects of design, monitoring, and analysis in trials of antiarrhythmic drugs are similar to those of other intervention studies, several features are different. These include decisions on how to identify the subjects, timing of the intervention with respect to the disease process, time of randomization, methods for measurement of outcome, and interim monitoring for harm or benefit. The resolution of these issues depends almost entirely on the specification of the question of interest."} {"id": "PMID:1279304", "title": "Development of class III antiarrhythmic agents.", "content": "Currently available antiarrhythmic agents that act by lengthening the action potential duration and refractory period exert most of their effect during bradycardia (class IIIB). Unfortunately, when these agents are most needed, i.e., during tachycardia, they lose most of their effect. In my opinion, ideally, antiarrhythmic agents need not change the electrophysiology of the normal sinus beat, but should lengthen refractoriness upon acceleration (class IIIA) of the heart until the refractory period exceeds the cycle length of the tachycardia. Three examples of how such class IIIA effects can be achieved are: (i) an upstroke-dependent activator of inward currents could form a universal class IIIA agent, (ii) a use-dependent blocker of iTO could be a great class IIIA agent in the atria, and (iii) a frequency-dependent blocker of late repolarizing currents (e.g., iKs) could be a good target for a ventricular agent.", "contents": "Development of class III antiarrhythmic agents. Currently available antiarrhythmic agents that act by lengthening the action potential duration and refractory period exert most of their effect during bradycardia (class IIIB). Unfortunately, when these agents are most needed, i.e., during tachycardia, they lose most of their effect. In my opinion, ideally, antiarrhythmic agents need not change the electrophysiology of the normal sinus beat, but should lengthen refractoriness upon acceleration (class IIIA) of the heart until the refractory period exceeds the cycle length of the tachycardia. Three examples of how such class IIIA effects can be achieved are: (i) an upstroke-dependent activator of inward currents could form a universal class IIIA agent, (ii) a use-dependent blocker of iTO could be a great class IIIA agent in the atria, and (iii) a frequency-dependent blocker of late repolarizing currents (e.g., iKs) could be a good target for a ventricular agent."} {"id": "PMID:1279305", "title": "Clinical implications of new insights into mechanism of antiarrhythmic drug action.", "content": "A classification system of antiarrhythmic drugs should help the clinician to select the optimal antiarrhythmic drug for a particular arrhythmia in an individual patient. This goal cannot be achieved by the Vaughan Williams classification system. Other important goals of this classification system were to provide the clinician with some information about proarrhythmic effects and about the possibility of combining particular antiarrhythmic agents. To date, a subdivision of class III antiarrhythmic agents has not been accomplished.", "contents": "Clinical implications of new insights into mechanism of antiarrhythmic drug action. A classification system of antiarrhythmic drugs should help the clinician to select the optimal antiarrhythmic drug for a particular arrhythmia in an individual patient. This goal cannot be achieved by the Vaughan Williams classification system. Other important goals of this classification system were to provide the clinician with some information about proarrhythmic effects and about the possibility of combining particular antiarrhythmic agents. To date, a subdivision of class III antiarrhythmic agents has not been accomplished."} {"id": "PMID:1279306", "title": "How to evaluate class III antiarrhythmic drug efficacy clinically: the benefits and shortcomings of the noninvasive approach.", "content": "Holter monitoring is the most commonly used noninvasive method for assessing antiarrhythmic drug therapy. It can easily be performed and we know the exact criteria for the definition of drug efficacy and the proarrhythmic effect. However, the value of Holter monitoring to predict clinical outcome in patients with malignant ventricular arrhythmias is controversial. Several authors claim that Holter monitoring is useless to evaluate antiarrhythmic drug effects. Theoretical considerations will explain that it is not the technique by itself that is useless; it is the way it is applied. Merely by changing the efficacy criteria, the value of Holter monitoring to assess antiarrhythmic effects can be improved significantly. Nevertheless, Holter monitoring is far from being the ideal method. It focuses only on arrhythmia density, denying that other risk factors such as heart rate variability, ischemia, and QT changes may be of additional prognostic value. Further studies with Holter monitoring should concentrate on the role of these parameters.", "contents": "How to evaluate class III antiarrhythmic drug efficacy clinically: the benefits and shortcomings of the noninvasive approach. Holter monitoring is the most commonly used noninvasive method for assessing antiarrhythmic drug therapy. It can easily be performed and we know the exact criteria for the definition of drug efficacy and the proarrhythmic effect. However, the value of Holter monitoring to predict clinical outcome in patients with malignant ventricular arrhythmias is controversial. Several authors claim that Holter monitoring is useless to evaluate antiarrhythmic drug effects. Theoretical considerations will explain that it is not the technique by itself that is useless; it is the way it is applied. Merely by changing the efficacy criteria, the value of Holter monitoring to assess antiarrhythmic effects can be improved significantly. Nevertheless, Holter monitoring is far from being the ideal method. It focuses only on arrhythmia density, denying that other risk factors such as heart rate variability, ischemia, and QT changes may be of additional prognostic value. Further studies with Holter monitoring should concentrate on the role of these parameters."} {"id": "PMID:1279307", "title": "How to evaluate class III antiarrhythmic drug efficacy clinically: the benefits and shortcomings of the invasive approach.", "content": "Ventricular tachycardia and ventricular fibrillation are frequent complications of organic heart disease. There is sufficient evidence that serial electrophysiologic testing is able to predict long-term efficacy of antiarrhythmic agents in patients with malignant ventricular tachyarrhythmias. This approach has not only been useful for the evaluation of class I drugs, but recent studies have shown that this invasive method may also be useful for the management of patients undergoing treatment with class III antiarrhythmic agents such as amiodarone and sotalol. The results of several studies suggest that class III agents are more effective than class I drugs in patients presenting with ventricular tachycardia or ventricular fibrillation. Proarrhythmic complications in patients treated with class III antiarrhythmic drugs are mainly characterized by torsades de pointes. Their incidence does not exceed 5%. Further studies are necessary to elucidate the mechanisms underlying this type of proarrhythmia. By the use of currently available stimulation techniques, patients who might develop torsades de pointes while on therapy with a class III agent cannot be identified.", "contents": "How to evaluate class III antiarrhythmic drug efficacy clinically: the benefits and shortcomings of the invasive approach. Ventricular tachycardia and ventricular fibrillation are frequent complications of organic heart disease. There is sufficient evidence that serial electrophysiologic testing is able to predict long-term efficacy of antiarrhythmic agents in patients with malignant ventricular tachyarrhythmias. This approach has not only been useful for the evaluation of class I drugs, but recent studies have shown that this invasive method may also be useful for the management of patients undergoing treatment with class III antiarrhythmic agents such as amiodarone and sotalol. The results of several studies suggest that class III agents are more effective than class I drugs in patients presenting with ventricular tachycardia or ventricular fibrillation. Proarrhythmic complications in patients treated with class III antiarrhythmic drugs are mainly characterized by torsades de pointes. Their incidence does not exceed 5%. Further studies are necessary to elucidate the mechanisms underlying this type of proarrhythmia. By the use of currently available stimulation techniques, patients who might develop torsades de pointes while on therapy with a class III agent cannot be identified."} {"id": "PMID:1279308", "title": "The utility of serum drug level monitoring during therapy with class III antiarrhythmic agents.", "content": "Serum drug level monitoring facilitates dosage optimization of agents with a narrow therapeutic index. Concentration-dependent antiarrhythmic and toxic effects have been demonstrated for several class I drugs, whereas the concentration-effect relationships of class III antiarrhythmics are less well established. The efficacy and toxicity of amiodarone, in particular, may be determined more by extensive tissue deposition than by its serum concentration. Furthermore, accumulation of the active metabolite desethylamiodarone seems to play an additional role. The antiarrhythmic serum concentration range of sotalol is wide; monitoring is not required. The clinical utility of serum concentration measurements with the newly developed class III antiarrhythmic agents remains to be evaluated in properly planned therapeutic trials in patients with supraventricular and ventricular arrhythmias.", "contents": "The utility of serum drug level monitoring during therapy with class III antiarrhythmic agents. Serum drug level monitoring facilitates dosage optimization of agents with a narrow therapeutic index. Concentration-dependent antiarrhythmic and toxic effects have been demonstrated for several class I drugs, whereas the concentration-effect relationships of class III antiarrhythmics are less well established. The efficacy and toxicity of amiodarone, in particular, may be determined more by extensive tissue deposition than by its serum concentration. Furthermore, accumulation of the active metabolite desethylamiodarone seems to play an additional role. The antiarrhythmic serum concentration range of sotalol is wide; monitoring is not required. The clinical utility of serum concentration measurements with the newly developed class III antiarrhythmic agents remains to be evaluated in properly planned therapeutic trials in patients with supraventricular and ventricular arrhythmias."} {"id": "PMID:1279309", "title": "Therapy with and assessment of class III antiarrhythmic agents in different patient populations.", "content": "The present article reviews the therapeutic efficacy of class III antiarrhythmic agents, particularly amiodarone, in patients with atrial and ventricular arrhythmias in the setting of different cardiac disorders. Both Holter monitoring and electrophysiologic studies appear to constitute reliable methods for evaluating the effects of class III agents and the long-term outcome in patients with a history of sustained ventricular tachycardia or fibrillation. The efficacy and tolerance of amiodarone in different patient populations is discussed.", "contents": "Therapy with and assessment of class III antiarrhythmic agents in different patient populations. The present article reviews the therapeutic efficacy of class III antiarrhythmic agents, particularly amiodarone, in patients with atrial and ventricular arrhythmias in the setting of different cardiac disorders. Both Holter monitoring and electrophysiologic studies appear to constitute reliable methods for evaluating the effects of class III agents and the long-term outcome in patients with a history of sustained ventricular tachycardia or fibrillation. The efficacy and tolerance of amiodarone in different patient populations is discussed."} {"id": "PMID:1279310", "title": "Clinical efficacy of long-term treatment with amiodarone for life-threatening arrhythmias.", "content": "The present article reviews the experience with amiodarone therapy in life-threatening ventricular tachyarrhythmias. In 13 studies, 1,594 patients were treated with amiodarone in average doses of 300 mg/day. The mean annual death rate was 6.2%; the annual withdrawal rate averaged 8%. Risk factors for arrhythmia recurrence despite amiodarone therapy were low left ventricular ejection fraction, inducible ventricular tachycardia by programmed electrical stimulation or persisting ventricular tachycardia on Holter monitoring, and cardiac arrest before the institution of amiodarone therapy. In these patients, additional antiarrhythmic measures such as an automatic implantable cardioverter/defibrillator or other surgical interventions must be considered.", "contents": "Clinical efficacy of long-term treatment with amiodarone for life-threatening arrhythmias. The present article reviews the experience with amiodarone therapy in life-threatening ventricular tachyarrhythmias. In 13 studies, 1,594 patients were treated with amiodarone in average doses of 300 mg/day. The mean annual death rate was 6.2%; the annual withdrawal rate averaged 8%. Risk factors for arrhythmia recurrence despite amiodarone therapy were low left ventricular ejection fraction, inducible ventricular tachycardia by programmed electrical stimulation or persisting ventricular tachycardia on Holter monitoring, and cardiac arrest before the institution of amiodarone therapy. In these patients, additional antiarrhythmic measures such as an automatic implantable cardioverter/defibrillator or other surgical interventions must be considered."} {"id": "PMID:1279311", "title": "Efficacy of intravenously administered amiodarone for short-term control of serious arrhythmias.", "content": "Intravenously administered amiodarone exerts substantial antiarrhythmic activity that is based on several different electrophysiologic mechanisms. Of these, the most important consists of an antitachycardic effect together with a significant prolongation of repolarization. The acute intravenous administration of amiodarone has been found to be effective in supraventricular and ventricular tachyarrhythmias resistant to conventional antiarrhythmic agents. Because amiodarone is free of detrimental hemodynamic effects in the majority of patients, intravenous administration of this compound seems to be particularly suitable in patients with serious arrhythmias in the setting of compromised left ventricular function.", "contents": "Efficacy of intravenously administered amiodarone for short-term control of serious arrhythmias. Intravenously administered amiodarone exerts substantial antiarrhythmic activity that is based on several different electrophysiologic mechanisms. Of these, the most important consists of an antitachycardic effect together with a significant prolongation of repolarization. The acute intravenous administration of amiodarone has been found to be effective in supraventricular and ventricular tachyarrhythmias resistant to conventional antiarrhythmic agents. Because amiodarone is free of detrimental hemodynamic effects in the majority of patients, intravenous administration of this compound seems to be particularly suitable in patients with serious arrhythmias in the setting of compromised left ventricular function."} {"id": "PMID:1279312", "title": "Drug combinations and interactions with class III agents.", "content": "Drug combinations with class III antiarrhythmic agents have not been studied systematically. There are data indicating that enhanced efficacy as evaluated by electrophysiologic studies can be obtained by combining sotalol and a type Ia drug or amiodarone with low-dose beta-blocking drugs. Combining amiodarone with a type Ia or Ic drug or with a beta-blocking drug can slow the rate of ventricular tachycardia to make the ventricular tachycardia hemodynamically well tolerated. Pharmacokinetic drug interactions with amiodarone are extensive. Recently, it has been shown that hepatic metabolism of amiodarone can be induced to enhance the conversion of amiodarone to N-desethylamiodarone. The physiologic effect of this drug transformation is uncertain. There should be few pharmacokinetic drug interactions with sotalol because this drug is almost completely absorbed, does not bind to plasma proteins, and is excreted unchanged by the kidneys.", "contents": "Drug combinations and interactions with class III agents. Drug combinations with class III antiarrhythmic agents have not been studied systematically. There are data indicating that enhanced efficacy as evaluated by electrophysiologic studies can be obtained by combining sotalol and a type Ia drug or amiodarone with low-dose beta-blocking drugs. Combining amiodarone with a type Ia or Ic drug or with a beta-blocking drug can slow the rate of ventricular tachycardia to make the ventricular tachycardia hemodynamically well tolerated. Pharmacokinetic drug interactions with amiodarone are extensive. Recently, it has been shown that hepatic metabolism of amiodarone can be induced to enhance the conversion of amiodarone to N-desethylamiodarone. The physiologic effect of this drug transformation is uncertain. There should be few pharmacokinetic drug interactions with sotalol because this drug is almost completely absorbed, does not bind to plasma proteins, and is excreted unchanged by the kidneys."} {"id": "PMID:1279313", "title": "Antiarrhythmic actions of DL-sotalol in ventricular and supraventricular arrhythmias.", "content": "DL-Sotalol is a unique antiarrhythmic agent combining potent beta-blocking properties with the propensity to prolong cardiac repolarization in all myocardial tissues. Its beta-blocker-associated negative inotropic effects are attenuated by its action potential-lengthening effect. The drug has an elimination half-life of 10-15 h. Sotalol's major electrophysiologic profile constitutes the summed effects of beta-blockade and prolonged repolarization. It exerts a potent antifibrillatory action modulated by its antiadrenergic effects. The effectiveness and tolerance of sotalol in a variety of atrial and ventricular dysrhythmias is reviewed in the present article.", "contents": "Antiarrhythmic actions of DL-sotalol in ventricular and supraventricular arrhythmias. DL-Sotalol is a unique antiarrhythmic agent combining potent beta-blocking properties with the propensity to prolong cardiac repolarization in all myocardial tissues. Its beta-blocker-associated negative inotropic effects are attenuated by its action potential-lengthening effect. The drug has an elimination half-life of 10-15 h. Sotalol's major electrophysiologic profile constitutes the summed effects of beta-blockade and prolonged repolarization. It exerts a potent antifibrillatory action modulated by its antiadrenergic effects. The effectiveness and tolerance of sotalol in a variety of atrial and ventricular dysrhythmias is reviewed in the present article."} {"id": "PMID:1279314", "title": "Differential analysis of frequency-dependent effects of antiarrhythmic drugs: importance of the saturation behavior of frequency-dependent sodium-channel blockade.", "content": "Frequency-dependent effects of class I antiarrhythmic drugs on Vmax reported in the literature are analyzed with respect to periodical drug binding to sodium channels. The analysis reveals that class I action can be differentiated according to the onset kinetics as well as to the saturation behavior of frequency-dependent sodium-channel blockade at increasing frequencies. As will be shown, class I drugs even of the same subclass (Ic) may differ markedly from each other with respect to the saturation behavior of frequency-dependent block. These findings may be of interest in view of the Cardiac Arrhythmia Suppression Trial (CAST) because the results found with flecainide and encainide in this study are usually extrapolated to other Ic drugs. Additionally, the influence of postrepolarization refractoriness caused by a class I drug on the action potential shortening during repetitive premature stimulation is compared with the effects of prolongation of absolute refractoriness induced by a class III drug.", "contents": "Differential analysis of frequency-dependent effects of antiarrhythmic drugs: importance of the saturation behavior of frequency-dependent sodium-channel blockade. Frequency-dependent effects of class I antiarrhythmic drugs on Vmax reported in the literature are analyzed with respect to periodical drug binding to sodium channels. The analysis reveals that class I action can be differentiated according to the onset kinetics as well as to the saturation behavior of frequency-dependent sodium-channel blockade at increasing frequencies. As will be shown, class I drugs even of the same subclass (Ic) may differ markedly from each other with respect to the saturation behavior of frequency-dependent block. These findings may be of interest in view of the Cardiac Arrhythmia Suppression Trial (CAST) because the results found with flecainide and encainide in this study are usually extrapolated to other Ic drugs. Additionally, the influence of postrepolarization refractoriness caused by a class I drug on the action potential shortening during repetitive premature stimulation is compared with the effects of prolongation of absolute refractoriness induced by a class III drug."} {"id": "PMID:1279315", "title": "Electrophysiologic and antiarrhythmic effects of D-sotalol.", "content": "There is extensive experimental and clinical experience concerning the antiarrhythmic potency of DL-sotalol, a beta-adrenergic antagonist that lengthens the cardiac action potential duration. More recently, its dextrorotatory isomer, D-sotalol, has been evaluated in experimental studies and preliminary clinical trials. Whereas the isomer is almost free of beta-blocking activity, both experimental and clinical data demonstrate that potent class III activity of D-sotalol. Further investigations, particularly in patients with life-threatening arrhythmias, are needed to delineate the clinical usefulness of this compound.", "contents": "Electrophysiologic and antiarrhythmic effects of D-sotalol. There is extensive experimental and clinical experience concerning the antiarrhythmic potency of DL-sotalol, a beta-adrenergic antagonist that lengthens the cardiac action potential duration. More recently, its dextrorotatory isomer, D-sotalol, has been evaluated in experimental studies and preliminary clinical trials. Whereas the isomer is almost free of beta-blocking activity, both experimental and clinical data demonstrate that potent class III activity of D-sotalol. Further investigations, particularly in patients with life-threatening arrhythmias, are needed to delineate the clinical usefulness of this compound."} {"id": "PMID:1279316", "title": "Dofetilide, a novel class III antiarrhythmic agent.", "content": "Dofetilide is a potent and selective class III antiarrhythmic agent that is under development for the treatment of re-entrant tachyarrhythmias (ventricular tachycardia/ventricular fibrillation, atrial fibrillation/atrial flutter, and paraoxysmal supraventricular tachycardia). In animal studies, dofetilide selectively inhibits the rapid component of the time-dependent outward potassium current (IKr) and therefore increases the effective refractory period and action potential duration without affecting the fast inward sodium current. Studies in dogs have shown that dofetilide (a) prolongs the effective refractory period in a dose-dependent manner, (b) elevates ventricular fibrillation threshold, (c) facilitates conversion of electrically induced ventricular fibrillation or fibrilloflutter to sinus rhythm, (d) does not influence conduction within the His-Purkinje system or within the myocardium, (e) does not impair cardiac contractility, and (f) reduces dispersion of ventricular repolarization. Dofetilide has been administered to healthy volunteers as well as to patients with ischemic heart disease or with supraventricular arrhythmias; the compound has generally been well tolerated. Side effects have occasionally been reported, but have generally been transient and mild and occur in placebo-treated subjects as well. No clinically significant changes in laboratory safety tests have been detected. The pharmacokinetic profile of dofetilide both in healthy volunteers and patients includes a linear dose-plasma concentration relationship and also a linear plasma concentration-QTc relationship. The terminal plasma elimination half-life is approximately 9-10 h and systemic bioavailability in the region of 100%. The elimination pattern is balanced, with 50% being excreted unchanged via the kidney, the remaining 50% being metabolized in the liver to inactive metabolites, with greater than 90% of circulating drug-related material being unchanged dofetilide. After intravenous administration of the compound, a slight hysteresis in the plasma drug level-QTc relationship has been detected. Pharmacodynamic data demonstrate dose- and concentration-dependent effects on myocardial repolarization as evidenced by prolongations of the QTc interval. This is reflected in significant prolongations in the effective and functional refractory periods and monophasic action potential duration throughout the myocardium. No effects on sinus node function, conduction parameters, or cardiac contractility have been detected in any of the clinical studies, supporting the contention that dofetilide is a highly selective class III antiarrhythmic agent.", "contents": "Dofetilide, a novel class III antiarrhythmic agent. Dofetilide is a potent and selective class III antiarrhythmic agent that is under development for the treatment of re-entrant tachyarrhythmias (ventricular tachycardia/ventricular fibrillation, atrial fibrillation/atrial flutter, and paraoxysmal supraventricular tachycardia). In animal studies, dofetilide selectively inhibits the rapid component of the time-dependent outward potassium current (IKr) and therefore increases the effective refractory period and action potential duration without affecting the fast inward sodium current. Studies in dogs have shown that dofetilide (a) prolongs the effective refractory period in a dose-dependent manner, (b) elevates ventricular fibrillation threshold, (c) facilitates conversion of electrically induced ventricular fibrillation or fibrilloflutter to sinus rhythm, (d) does not influence conduction within the His-Purkinje system or within the myocardium, (e) does not impair cardiac contractility, and (f) reduces dispersion of ventricular repolarization. Dofetilide has been administered to healthy volunteers as well as to patients with ischemic heart disease or with supraventricular arrhythmias; the compound has generally been well tolerated. Side effects have occasionally been reported, but have generally been transient and mild and occur in placebo-treated subjects as well. No clinically significant changes in laboratory safety tests have been detected. The pharmacokinetic profile of dofetilide both in healthy volunteers and patients includes a linear dose-plasma concentration relationship and also a linear plasma concentration-QTc relationship. The terminal plasma elimination half-life is approximately 9-10 h and systemic bioavailability in the region of 100%. The elimination pattern is balanced, with 50% being excreted unchanged via the kidney, the remaining 50% being metabolized in the liver to inactive metabolites, with greater than 90% of circulating drug-related material being unchanged dofetilide. After intravenous administration of the compound, a slight hysteresis in the plasma drug level-QTc relationship has been detected. Pharmacodynamic data demonstrate dose- and concentration-dependent effects on myocardial repolarization as evidenced by prolongations of the QTc interval. This is reflected in significant prolongations in the effective and functional refractory periods and monophasic action potential duration throughout the myocardium. No effects on sinus node function, conduction parameters, or cardiac contractility have been detected in any of the clinical studies, supporting the contention that dofetilide is a highly selective class III antiarrhythmic agent."} {"id": "PMID:1279317", "title": "Chromosome aberrations of human small cell lung cancer induced by a new 111In-bleomycin complex.", "content": "A new 111Indium labeled bleomycin complex (111In-BLMC) was prepared and found to be effective for tumor imaging and therapy both in mouse glioma and human small cell lung cancer (SCLC) cells. Chromosome aberrations were studied in human SCLC cells to explore its mechanisms of killing cancer cells. SCLC cells (N417) were exposed to 111In-BLMC, BLM, or 111InCl3 (for control) for 1 hour, treated with colcemid, and chromosomal changes were analyzed. A dramatic increase in chromatic gaps, breaks, chromosome breaks, double minutes, rings, triradii, quadriradii, and chromosome stickiness were observed in the cells treated by 111In-BLMC compared to BLM or 111InCl3. These results indicated that 111In-BLMC has therapeutic potential for combination chemo-radiotherapy of cancer (e.g., by Auger electrons and local energy deposition).", "contents": "Chromosome aberrations of human small cell lung cancer induced by a new 111In-bleomycin complex. A new 111Indium labeled bleomycin complex (111In-BLMC) was prepared and found to be effective for tumor imaging and therapy both in mouse glioma and human small cell lung cancer (SCLC) cells. Chromosome aberrations were studied in human SCLC cells to explore its mechanisms of killing cancer cells. SCLC cells (N417) were exposed to 111In-BLMC, BLM, or 111InCl3 (for control) for 1 hour, treated with colcemid, and chromosomal changes were analyzed. A dramatic increase in chromatic gaps, breaks, chromosome breaks, double minutes, rings, triradii, quadriradii, and chromosome stickiness were observed in the cells treated by 111In-BLMC compared to BLM or 111InCl3. These results indicated that 111In-BLMC has therapeutic potential for combination chemo-radiotherapy of cancer (e.g., by Auger electrons and local energy deposition)."} {"id": "PMID:1279318", "title": "Early palliation of univentricular hearts with subaortic stenosis and ventriculoarterial discordance. The arterial switch option.", "content": "The optimal Fontan-type operation greatly depends on appropriate initial palliation. Several surgical techniques have been used in infancy to palliate patients with univentricular hearts, ventriculoarterial discordance, and subaortic stenosis. The two most common are pulmonary artery banding and Damus-Norwood procedures. Palliative arterial switch operation is another surgical option that was used in this early series of seven infants. The principle of this operation is to \"switch\" the subaortic obstruction into a subpulmonary obstruction; the coronary artery relocation on the large pulmonary trunk creates a harmonious aortic root and the connection of the rudimentary ventricular chamber to the pulmonary artery trunk creates a natural protection of the pulmonary vascular bed through the restrictive bulboventricular foramen. Seven infants with univentricular hearts, ventriculoarterial discordance, and subaortic stenosis underwent a palliative arterial switch operation. All infants had an associated aortic arch obstruction of various degrees, including one with interrupted aortic arch, five with coarctation with severe arch hypoplasia, and one with isolated arch hypoplasia. There were three with double-inlet left ventricle, three with tricuspid atresia, and one with transposition of the great arteries with ventricular septal defect and severe right ventricular hypoplasia. The subaortic obstruction was patent at birth in five patients who underwent a palliative switch operation in the first 2 months of life, and rapidly occurred following a previous neonatal pulmonary artery banding associated with arch repair in two patients who underwent a switch operation at 5 and 8 months of age, respectively. The operation includes aortic arch repair without prosthetic material, an atrial septectomy, and the arterial switch. An associated pulmonary shunt was required in five patients and a pulmonary artery banding in one. There was one early death in a patient with [S,L,L] anatomy and congenital atrioventricular block, leading to an early mortality of 14% (95% confidence limits: 1% to 28%). There was one late death. Four survivors are waiting for a Fontan-type procedure, and one survivor had satisfactory right ventricular growth. Early palliative arterial switch operation offers several advantages: reconstruction of a harmonious aortic root, natural protection of the pulmonary bed through the restrictive bulboventricular foramen, prevention of deleterious myocardial hypertrophy, and arch reconstruction without the introduction of a foreign material. This aggressive technique may provide a satisfactory palliation in infants with univentricular hearts and ventriculoarterial discordance, when the bulboventricular foramen/aortic anulus ratio is less than 0.8 or when the subaortic stenosis is severe enough to be associated with an arch obstruction.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Early palliation of univentricular hearts with subaortic stenosis and ventriculoarterial discordance. The arterial switch option. The optimal Fontan-type operation greatly depends on appropriate initial palliation. Several surgical techniques have been used in infancy to palliate patients with univentricular hearts, ventriculoarterial discordance, and subaortic stenosis. The two most common are pulmonary artery banding and Damus-Norwood procedures. Palliative arterial switch operation is another surgical option that was used in this early series of seven infants. The principle of this operation is to \"switch\" the subaortic obstruction into a subpulmonary obstruction; the coronary artery relocation on the large pulmonary trunk creates a harmonious aortic root and the connection of the rudimentary ventricular chamber to the pulmonary artery trunk creates a natural protection of the pulmonary vascular bed through the restrictive bulboventricular foramen. Seven infants with univentricular hearts, ventriculoarterial discordance, and subaortic stenosis underwent a palliative arterial switch operation. All infants had an associated aortic arch obstruction of various degrees, including one with interrupted aortic arch, five with coarctation with severe arch hypoplasia, and one with isolated arch hypoplasia. There were three with double-inlet left ventricle, three with tricuspid atresia, and one with transposition of the great arteries with ventricular septal defect and severe right ventricular hypoplasia. The subaortic obstruction was patent at birth in five patients who underwent a palliative switch operation in the first 2 months of life, and rapidly occurred following a previous neonatal pulmonary artery banding associated with arch repair in two patients who underwent a switch operation at 5 and 8 months of age, respectively. The operation includes aortic arch repair without prosthetic material, an atrial septectomy, and the arterial switch. An associated pulmonary shunt was required in five patients and a pulmonary artery banding in one. There was one early death in a patient with [S,L,L] anatomy and congenital atrioventricular block, leading to an early mortality of 14% (95% confidence limits: 1% to 28%). There was one late death. Four survivors are waiting for a Fontan-type procedure, and one survivor had satisfactory right ventricular growth. Early palliative arterial switch operation offers several advantages: reconstruction of a harmonious aortic root, natural protection of the pulmonary bed through the restrictive bulboventricular foramen, prevention of deleterious myocardial hypertrophy, and arch reconstruction without the introduction of a foreign material. This aggressive technique may provide a satisfactory palliation in infants with univentricular hearts and ventriculoarterial discordance, when the bulboventricular foramen/aortic anulus ratio is less than 0.8 or when the subaortic stenosis is severe enough to be associated with an arch obstruction.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279319", "title": "Combination use of suboptimal dose of FK 506 and cyclosporine in canine lung transplantation.", "content": "The immunosuppressive potency and the side effects of combination therapy with FK 506 and cyclosporine A were studied in dogs that had undergone lung transplantation. The animals were divided into four groups: group A (one third optimal FK 506 dose: FK 506, 0.03 mg/kg intramuscularly) (n = 5), group B (one third optimal cyclosporine dose: cyclosporine 6 mg/kg orally) (n = 5), group C (one third FK 506 and one third cyclosporine optimal doses): FK 506, 0.03 mg/kg intramuscularly plus cyclosporine 6 mg/kg orally) (n = 5), and group D (half FK 506 plus half cyclosporine optimal doses: FK 506, 0.05 mg/kg intramuscularly, plus cyclosporine, 10 mg/kg orally) (n = 10). Assessments including chest x-ray film, fiberoptic bronchoscopy, hematologic and biochemical tests, FK 506 and cyclosporine blood trough level measurement, right pulmonary artery occlusion test, and histopathologic observations were performed. In group A two of five dogs survived 28 days and three died on postoperative days 7, 14, and 21. In group B one dog survived 28 days and four died on postoperative days 9 (two dogs), 14, and 21. Histologic examination showed severe rejection in both group A and group B. In group C all five dogs survived 28 days but showed mild rejection. In group D one dog died of intestinal bleeding on postoperative day 7 and nine survived 28 days. No pathologic changes were observed except in one case of mild rejection. The ventilation function of the transplanted lung was poor in groups A, B, and C but good in group D. No abnormal rise of FK 506 and cyclosporine trough levels was observed. There were no significant side effects and abnormal hematologic and biochemical data except in one dog in group D. We concluded (1) the combination of FK 506, 0.03 mg/kg, and cyclosporine, 6 mg/kg, is much more effective than either drug used singly, (2) the combination of FK 506, 0.05 mg/kg, and cyclosporine, 10 mg/kg, prevents rejection with tolerable side effects, and (3) no worse side effects are caused by combination therapy with FK 506 and cyclosporine than by either one used singly.", "contents": "Combination use of suboptimal dose of FK 506 and cyclosporine in canine lung transplantation. The immunosuppressive potency and the side effects of combination therapy with FK 506 and cyclosporine A were studied in dogs that had undergone lung transplantation. The animals were divided into four groups: group A (one third optimal FK 506 dose: FK 506, 0.03 mg/kg intramuscularly) (n = 5), group B (one third optimal cyclosporine dose: cyclosporine 6 mg/kg orally) (n = 5), group C (one third FK 506 and one third cyclosporine optimal doses): FK 506, 0.03 mg/kg intramuscularly plus cyclosporine 6 mg/kg orally) (n = 5), and group D (half FK 506 plus half cyclosporine optimal doses: FK 506, 0.05 mg/kg intramuscularly, plus cyclosporine, 10 mg/kg orally) (n = 10). Assessments including chest x-ray film, fiberoptic bronchoscopy, hematologic and biochemical tests, FK 506 and cyclosporine blood trough level measurement, right pulmonary artery occlusion test, and histopathologic observations were performed. In group A two of five dogs survived 28 days and three died on postoperative days 7, 14, and 21. In group B one dog survived 28 days and four died on postoperative days 9 (two dogs), 14, and 21. Histologic examination showed severe rejection in both group A and group B. In group C all five dogs survived 28 days but showed mild rejection. In group D one dog died of intestinal bleeding on postoperative day 7 and nine survived 28 days. No pathologic changes were observed except in one case of mild rejection. The ventilation function of the transplanted lung was poor in groups A, B, and C but good in group D. No abnormal rise of FK 506 and cyclosporine trough levels was observed. There were no significant side effects and abnormal hematologic and biochemical data except in one dog in group D. We concluded (1) the combination of FK 506, 0.03 mg/kg, and cyclosporine, 6 mg/kg, is much more effective than either drug used singly, (2) the combination of FK 506, 0.05 mg/kg, and cyclosporine, 10 mg/kg, prevents rejection with tolerable side effects, and (3) no worse side effects are caused by combination therapy with FK 506 and cyclosporine than by either one used singly."} {"id": "PMID:1279320", "title": "An improved HRP method for tracing axons in whole-mount preparations during early stages of regeneration in peripheral nerves of adult animals.", "content": "An improved method using HRP for visualizing axons in whole-mount preparations is described. Application of this method to preparations of regenerating frog peripheral nerves maintained in organ culture was used to show that regeneration following nerve crush begins after about 3 days.", "contents": "An improved HRP method for tracing axons in whole-mount preparations during early stages of regeneration in peripheral nerves of adult animals. An improved method using HRP for visualizing axons in whole-mount preparations is described. Application of this method to preparations of regenerating frog peripheral nerves maintained in organ culture was used to show that regeneration following nerve crush begins after about 3 days."} {"id": "PMID:1279321", "title": "Quantitative microdialysis of dopamine in the striatum: effect of circadian variation.", "content": "Two quantitative microdialysis methods were used to determine the concentration of extracellular dopamine in the anterior striatum of the rat. In the first method, the slow perfusion flow rate method, perfusion was at 57 nl/min and dialysate samples were collected every 90 min for 18 h and assayed for dopamine (DA), DOPAC (3,4-dihydroxy-phenylacetic acid), homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA). There was a significant increase in the concentration of dopamine during the dark cycle compared with the light cycle (14.7 +/- 1 nM vs. 9.3 +/- 0.7 nM; mean +/- SEM; P less than 0.0001), indicating possible circadian variations in the extracellular concentration of DA. There was a steady decrease in the level of DOPAC and HVA, and no change in the level of 5-HIAA. For the point of no-net-flux method, animals were perfused with 4 concentrations of DA or DOPAC, bracketing the extracellular concentrations. The extracellular concentrations of DA and DOPAC using this method were 10.2 +/- 1.7 nM and 17.4 +/- 2.6 microM, respectively. The in vivo recoveries for DA and DOPAC as derived from the slope of the linear regression curves were 72 +/- 3% and 43 +/- 5%. These values were shown to be significantly different (P less than 0.001). Both methods gave similar results for the level of DA in the striatum.", "contents": "Quantitative microdialysis of dopamine in the striatum: effect of circadian variation. Two quantitative microdialysis methods were used to determine the concentration of extracellular dopamine in the anterior striatum of the rat. In the first method, the slow perfusion flow rate method, perfusion was at 57 nl/min and dialysate samples were collected every 90 min for 18 h and assayed for dopamine (DA), DOPAC (3,4-dihydroxy-phenylacetic acid), homovanillic acid (HVA) and 5-hydroxy-indoleacetic acid (5-HIAA). There was a significant increase in the concentration of dopamine during the dark cycle compared with the light cycle (14.7 +/- 1 nM vs. 9.3 +/- 0.7 nM; mean +/- SEM; P less than 0.0001), indicating possible circadian variations in the extracellular concentration of DA. There was a steady decrease in the level of DOPAC and HVA, and no change in the level of 5-HIAA. For the point of no-net-flux method, animals were perfused with 4 concentrations of DA or DOPAC, bracketing the extracellular concentrations. The extracellular concentrations of DA and DOPAC using this method were 10.2 +/- 1.7 nM and 17.4 +/- 2.6 microM, respectively. The in vivo recoveries for DA and DOPAC as derived from the slope of the linear regression curves were 72 +/- 3% and 43 +/- 5%. These values were shown to be significantly different (P less than 0.001). Both methods gave similar results for the level of DA in the striatum."} {"id": "PMID:1279322", "title": "Enzyme-histochemistry of the foreskin microvasculature using fructose-1,6-diphosphatase.", "content": "Microvascular capillaries (blood and lymph) in human foreskin were examined for staining characteristics for fructose-1,6-diphosphatase (FDPase). Based on enzyme-histochemistry and electron microscopy, both blood and lymph vessels and microvessels as well as dermal smooth muscle all stain positively but with varying intensity for FDPase.", "contents": "Enzyme-histochemistry of the foreskin microvasculature using fructose-1,6-diphosphatase. Microvascular capillaries (blood and lymph) in human foreskin were examined for staining characteristics for fructose-1,6-diphosphatase (FDPase). Based on enzyme-histochemistry and electron microscopy, both blood and lymph vessels and microvessels as well as dermal smooth muscle all stain positively but with varying intensity for FDPase."} {"id": "PMID:1279323", "title": "Inhibitors of proteases prevent endonucleolysis accompanying apoptotic death of HL-60 leukemic cells and normal thymocytes.", "content": "Exposure of human promyelocytic leukemic HL-60 cells to the topoisomerase I inhibitor camptothecin (CAM) triggers endonucleolytic activity and apoptotic death of these cells. The nucleolytic effect is seen 2-4 h after drug addition and is highly selective to cells progressing through S phase. Concomitant with degradation of DNA, which is preferential to the nucleosomal DNA linker sections, extensive proteolysis takes place in these cells. Cellular RNA, however, is initially degraded to a much lesser degree than DNA or protein. Both endonucleolysis and proteolysis triggered by CAM in S-phase HL-60 cells can be prevented by the protease inhibitors N-tosyl-L-phenylalanylchloromethyl ketone (TPCK), N-tosyl-L-lysylchloromethyl ketone (TLCK) or partly by N-tosyl-L-arginine methyl ester (TAME), added simultaneously with CAM, or up to 30 min after exposure to CAM, at their respective concentrations known to inhibit proteases. The protective effect of these protease inhibitors on DNA degradation cannot be due to the suppression of cell progression through S phase because cells still replicate DNA in their presence, albeit at a reduced rate. Furthermore, TPCK and TLCK protect rat thymocytes against endonucleolysis induced by prednisolone. In the latter cell system, (considered a classic model of apoptosis), endonucleolysis, which primarily affects G0/G1 cells, is unrelated to cell progression through S phase. The present data suggest that the endonucleolysis and proteolysis which accompany apoptotic cell death are coupled, and the proteolytic step is needed for DNA degradation to occur.", "contents": "Inhibitors of proteases prevent endonucleolysis accompanying apoptotic death of HL-60 leukemic cells and normal thymocytes. Exposure of human promyelocytic leukemic HL-60 cells to the topoisomerase I inhibitor camptothecin (CAM) triggers endonucleolytic activity and apoptotic death of these cells. The nucleolytic effect is seen 2-4 h after drug addition and is highly selective to cells progressing through S phase. Concomitant with degradation of DNA, which is preferential to the nucleosomal DNA linker sections, extensive proteolysis takes place in these cells. Cellular RNA, however, is initially degraded to a much lesser degree than DNA or protein. Both endonucleolysis and proteolysis triggered by CAM in S-phase HL-60 cells can be prevented by the protease inhibitors N-tosyl-L-phenylalanylchloromethyl ketone (TPCK), N-tosyl-L-lysylchloromethyl ketone (TLCK) or partly by N-tosyl-L-arginine methyl ester (TAME), added simultaneously with CAM, or up to 30 min after exposure to CAM, at their respective concentrations known to inhibit proteases. The protective effect of these protease inhibitors on DNA degradation cannot be due to the suppression of cell progression through S phase because cells still replicate DNA in their presence, albeit at a reduced rate. Furthermore, TPCK and TLCK protect rat thymocytes against endonucleolysis induced by prednisolone. In the latter cell system, (considered a classic model of apoptosis), endonucleolysis, which primarily affects G0/G1 cells, is unrelated to cell progression through S phase. The present data suggest that the endonucleolysis and proteolysis which accompany apoptotic cell death are coupled, and the proteolytic step is needed for DNA degradation to occur."} {"id": "PMID:1279324", "title": "The significance of CD34 and TdT determinations in patients with untreated de novo acute myeloid leukemia.", "content": "The results of intensive chemotherapy given to 247 adults at the University of Maryland Cancer Center with previously untreated de novo acute myeloid leukemia (AML) were reviewed with respect to expression of terminal deoxynucleotidyl transferase (TdT) and CD34. Of the 228 patients with data for TdT, 32 (14%) had > 5% of the leukemia cells positive by an immunofluorescence assay. The median age of the TdT-positive patients was approximately 10 years less than the TdT-negative patients (50 versus 60 years). Patients with TdT-positive AML had similar median survival (12 versus 10.5 months) and complete remission (CR) rates (53 versus 59%), but a greater frequency of long-term complete responders (60 of complete remitters versus 20%, p = 0.08) than TdT-negative patients. Of 126 patients tested, 59% were CD34-negative (< 20% reactivity with leukemia cells). These 74 patients (median age 60 years) had a greater CR rate (71 versus 48%, p = 0.008) than the 52 CD34-positive patients (median age 60 years), and improved survival (p = 0.013 by Wilcoxon) although there was no difference in the duration of CR between the CD34-positive and negative groups. Of CD34-positive patients 12/52 remain in continuous CR, and 16/74 CD34-negative patients remain in continuous CR. None of eight patients strongly positive for CD34 (> 70% reactivity) remain disease-free. Positivity for TdT or CD34 was associated with less differentiated AML. Of CD34-positive patients, 44% had FAB M0/M1 morphology versus 13% of CD34-negative patients (p = 0.0001); similarly, 47% of TdT-positive patients were FAB M0/ML1 versus 25% of TdT-negative patients (p = 0.01). Of seven patients with FAB M4E0, five were CD34-positive. Of the 12 CD34-positive survivors, four had FAB M4E0. Thus CD34 expression predicts for CR rate and overall survival in adults with AML. TdT expression does not significantly affect overall outcome but may be associated with longer CR durations.", "contents": "The significance of CD34 and TdT determinations in patients with untreated de novo acute myeloid leukemia. The results of intensive chemotherapy given to 247 adults at the University of Maryland Cancer Center with previously untreated de novo acute myeloid leukemia (AML) were reviewed with respect to expression of terminal deoxynucleotidyl transferase (TdT) and CD34. Of the 228 patients with data for TdT, 32 (14%) had > 5% of the leukemia cells positive by an immunofluorescence assay. The median age of the TdT-positive patients was approximately 10 years less than the TdT-negative patients (50 versus 60 years). Patients with TdT-positive AML had similar median survival (12 versus 10.5 months) and complete remission (CR) rates (53 versus 59%), but a greater frequency of long-term complete responders (60 of complete remitters versus 20%, p = 0.08) than TdT-negative patients. Of 126 patients tested, 59% were CD34-negative (< 20% reactivity with leukemia cells). These 74 patients (median age 60 years) had a greater CR rate (71 versus 48%, p = 0.008) than the 52 CD34-positive patients (median age 60 years), and improved survival (p = 0.013 by Wilcoxon) although there was no difference in the duration of CR between the CD34-positive and negative groups. Of CD34-positive patients 12/52 remain in continuous CR, and 16/74 CD34-negative patients remain in continuous CR. None of eight patients strongly positive for CD34 (> 70% reactivity) remain disease-free. Positivity for TdT or CD34 was associated with less differentiated AML. Of CD34-positive patients, 44% had FAB M0/M1 morphology versus 13% of CD34-negative patients (p = 0.0001); similarly, 47% of TdT-positive patients were FAB M0/ML1 versus 25% of TdT-negative patients (p = 0.01). Of seven patients with FAB M4E0, five were CD34-positive. Of the 12 CD34-positive survivors, four had FAB M4E0. Thus CD34 expression predicts for CR rate and overall survival in adults with AML. TdT expression does not significantly affect overall outcome but may be associated with longer CR durations."} {"id": "PMID:1279325", "title": "The effect of recombinant GM-CSF and G-CSF on the bone marrow cells of children with acute lymphoblastic leukemia.", "content": "Colony stimulating factors (CSFs) are glycoprotein hormones that regulate growth and differentiation of hematopoietic progenitor cells. Their use to stimulate granulocyte precursors during periods of neutropenia in patients with acute myeloid leukemia (AML) is limited by their concomitant stimulation of the proliferation of myeloblasts. The effects of these agents on leukemic lymphoblasts is not entirely known. We have investigated the in vitro effects of granulocyte-CSF (G-CSF) and granulocyte/macrophage-CSF (GM-CSF) on leukemic cells from children with acute lymphoblastic leukemia (ALL). DNA synthesis of bone marrow cells from 22 children with ALL, either at diagnosis or in relapse, was examined with and without CSFs. Proliferative potential was also tested in a clonogenic assay with 13 bone marrow specimens. These factors did not stimulate the growth of ALL cells in either assay. Our results indicate that G-CSF and GM-CSF should be able to stimulate granulocyte proliferation without enhancing leukemic proliferation during periods of neutropenia in children with ALL.", "contents": "The effect of recombinant GM-CSF and G-CSF on the bone marrow cells of children with acute lymphoblastic leukemia. Colony stimulating factors (CSFs) are glycoprotein hormones that regulate growth and differentiation of hematopoietic progenitor cells. Their use to stimulate granulocyte precursors during periods of neutropenia in patients with acute myeloid leukemia (AML) is limited by their concomitant stimulation of the proliferation of myeloblasts. The effects of these agents on leukemic lymphoblasts is not entirely known. We have investigated the in vitro effects of granulocyte-CSF (G-CSF) and granulocyte/macrophage-CSF (GM-CSF) on leukemic cells from children with acute lymphoblastic leukemia (ALL). DNA synthesis of bone marrow cells from 22 children with ALL, either at diagnosis or in relapse, was examined with and without CSFs. Proliferative potential was also tested in a clonogenic assay with 13 bone marrow specimens. These factors did not stimulate the growth of ALL cells in either assay. Our results indicate that G-CSF and GM-CSF should be able to stimulate granulocyte proliferation without enhancing leukemic proliferation during periods of neutropenia in children with ALL."} {"id": "PMID:1279327", "title": "Hairy cell leukemia 1992.", "content": "Hairy cell leukemia (HCL) is an uncommon chronic lymphoproliferative disorder, its treatment requires continuous update. Splenectomy as first line therapy has few indications; recombinant alfa interferon (IFN) leads to a high overall response rate but there are few bone marrow remissions; deoxycoformycin (dCF) or pentostatin leads to a higher complete bone marrow response rate than with IFN but follow-up biopsies show persistence of hairy cells; 2-chlorodeoxyadenosine (2-CdA) is a purine analog that after a single seven day intravenous infusion leads to a complete response rate. 2-CDA will probably become the drug of choice for first line therapy for HCL.", "contents": "Hairy cell leukemia 1992. Hairy cell leukemia (HCL) is an uncommon chronic lymphoproliferative disorder, its treatment requires continuous update. Splenectomy as first line therapy has few indications; recombinant alfa interferon (IFN) leads to a high overall response rate but there are few bone marrow remissions; deoxycoformycin (dCF) or pentostatin leads to a higher complete bone marrow response rate than with IFN but follow-up biopsies show persistence of hairy cells; 2-chlorodeoxyadenosine (2-CdA) is a purine analog that after a single seven day intravenous infusion leads to a complete response rate. 2-CDA will probably become the drug of choice for first line therapy for HCL."} {"id": "PMID:1279329", "title": "Interactions of colony stimulating factors, other modulating cytokines and hematopoietic progenitor cells. Laboratory and clinical studies.", "content": "Blood cell production is regulated by a complex interacting network of stem and progenitor cells, from which all the blood forming elements are derived, and the effects of cytokines which can up- or down-modulate proliferation or self-renewal of stem and progenitor cells (1,2). This report reviews in brief recent information on the characteristics of human umbilical cord blood progenitor cells, the effects of the potent co-stimulating molecule, steel factor, and the myelosuppressive effects of macrophage inflammatory protein 1 alpha and other members of this latter group of molecules termed cytokines. In vitro as well as preclinical and clinical in vivo effects are covered.", "contents": "Interactions of colony stimulating factors, other modulating cytokines and hematopoietic progenitor cells. Laboratory and clinical studies. Blood cell production is regulated by a complex interacting network of stem and progenitor cells, from which all the blood forming elements are derived, and the effects of cytokines which can up- or down-modulate proliferation or self-renewal of stem and progenitor cells (1,2). This report reviews in brief recent information on the characteristics of human umbilical cord blood progenitor cells, the effects of the potent co-stimulating molecule, steel factor, and the myelosuppressive effects of macrophage inflammatory protein 1 alpha and other members of this latter group of molecules termed cytokines. In vitro as well as preclinical and clinical in vivo effects are covered."} {"id": "PMID:1279330", "title": "Differential gene expression between young and senescent, quiescent WI-38 cells.", "content": "To investigate age-related changes in gene expression in WI-38 cells, we isolated RNA from young and senescent, quiescent cultures and made subtracted cDNA libraries. Density-arrested cells were incubated in serum-free MCDB-104 for 3 days. RNA was then isolated and subtracted cDNA libraries were made in the phagemid vector pCDM8. Both by picking clones at random from these subtracted libraries and by differential hybridization screening with subtracted cDNA probes from young and senescent cells, we have identified a total of 11 genes for which RNA is expressed differentially in these quiescent young and senescent WI-38 cultures. Two genes, EPC-1 and EPC-A2, with elevated RNA levels in young cells, have sequences which have not previously been identified. Two of the genes with elevated RNA expression in the senescent cells are the mitochondria-coded genes for NADH dehydrogenase subunit 4 and for cytochrome b. We also identified seven other genes with elevated RNA levels in senescent cells. Three of these, LPC-1, LPC-14 and LPC-24, have been partially sequenced and have not previously been identified. These studies show that density-arrested, serum-deprived, quiescent young and senescent cells express a number of genes differentially. These differences are not growth-dependent, but are age-dependent. Our studies also show that the methods employed here, which include careful regulation of the cell cultures and subtraction of the libraries, result in libraries from which differentially expressed genes can be identified, either by random selection or by differential hybridization screening with subtracted probes.", "contents": "Differential gene expression between young and senescent, quiescent WI-38 cells. To investigate age-related changes in gene expression in WI-38 cells, we isolated RNA from young and senescent, quiescent cultures and made subtracted cDNA libraries. Density-arrested cells were incubated in serum-free MCDB-104 for 3 days. RNA was then isolated and subtracted cDNA libraries were made in the phagemid vector pCDM8. Both by picking clones at random from these subtracted libraries and by differential hybridization screening with subtracted cDNA probes from young and senescent cells, we have identified a total of 11 genes for which RNA is expressed differentially in these quiescent young and senescent WI-38 cultures. Two genes, EPC-1 and EPC-A2, with elevated RNA levels in young cells, have sequences which have not previously been identified. Two of the genes with elevated RNA expression in the senescent cells are the mitochondria-coded genes for NADH dehydrogenase subunit 4 and for cytochrome b. We also identified seven other genes with elevated RNA levels in senescent cells. Three of these, LPC-1, LPC-14 and LPC-24, have been partially sequenced and have not previously been identified. These studies show that density-arrested, serum-deprived, quiescent young and senescent cells express a number of genes differentially. These differences are not growth-dependent, but are age-dependent. Our studies also show that the methods employed here, which include careful regulation of the cell cultures and subtraction of the libraries, result in libraries from which differentially expressed genes can be identified, either by random selection or by differential hybridization screening with subtracted probes."} {"id": "PMID:1279332", "title": "Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer.", "content": "Animal models suggest a role for new vessel formation (angiogenesis) in tumours with metastatic potential, and there is some evidence that this is true for human tumours. What is needed is a sensitive and specific label for endothelial cells, and one candidate would be a monoclonal antibody to platelet/endothelial cell adhesion molecule (PECAM). We have counted microvessels in 103 primary breast cancers using the JC70 antibody to PECAM (or CD31). We compared our findings with various pathological indicators (lymph node status and tumour grade, size, and type and markers (oestrogen receptor, and c-erbB-2 expression and detection of mutant p53). Tumours showed significantly higher vascularisation than normal breast tissue and the number of blood vessels/mm2 was significantly associated with node metastasis. Only 2 out of 50 tumours with 99 vessel/mm2 or less were node positive whereas 31 out of 39 tumours with counts above 140/mm2 were positive (p < 0.0001). Tumour size and grade also correlated with node metastasis and vascularisation also increased with the size of the primary and with poor differentiation. However, within each subgroup of size or differentiation tumours without node involvement had much lower vascular counts, and multivariate analysis showed that vascular count alone explains the association of size and grade with node metastasis. Other markers, conventional or novel, did not correlate with vascularisation. Even with the short follow-up in this series, vascular counts correlated with early death. These results suggest that angiogenesis is closely linked to metastasis, that it is acquired at a critical density of vessels, and that this process occurs as tumours enlarge or become more poorly differentiated. Counting of newly formed microvessels stained with endothelium-specific antibodies may prove to be a useful tool in the early detection of metastatic potential and in the selection of patients for whom anti-angiogenesis drugs might be beneficial.", "contents": "Angiogenesis, assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Animal models suggest a role for new vessel formation (angiogenesis) in tumours with metastatic potential, and there is some evidence that this is true for human tumours. What is needed is a sensitive and specific label for endothelial cells, and one candidate would be a monoclonal antibody to platelet/endothelial cell adhesion molecule (PECAM). We have counted microvessels in 103 primary breast cancers using the JC70 antibody to PECAM (or CD31). We compared our findings with various pathological indicators (lymph node status and tumour grade, size, and type and markers (oestrogen receptor, and c-erbB-2 expression and detection of mutant p53). Tumours showed significantly higher vascularisation than normal breast tissue and the number of blood vessels/mm2 was significantly associated with node metastasis. Only 2 out of 50 tumours with 99 vessel/mm2 or less were node positive whereas 31 out of 39 tumours with counts above 140/mm2 were positive (p < 0.0001). Tumour size and grade also correlated with node metastasis and vascularisation also increased with the size of the primary and with poor differentiation. However, within each subgroup of size or differentiation tumours without node involvement had much lower vascular counts, and multivariate analysis showed that vascular count alone explains the association of size and grade with node metastasis. Other markers, conventional or novel, did not correlate with vascularisation. Even with the short follow-up in this series, vascular counts correlated with early death. These results suggest that angiogenesis is closely linked to metastasis, that it is acquired at a critical density of vessels, and that this process occurs as tumours enlarge or become more poorly differentiated. Counting of newly formed microvessels stained with endothelium-specific antibodies may prove to be a useful tool in the early detection of metastatic potential and in the selection of patients for whom anti-angiogenesis drugs might be beneficial."} {"id": "PMID:1279337", "title": "Effects of chronic clonidine administration on parasympathetic-evoked rat saliva.", "content": "Effects of chronic administration of clonidine on parasympathetic-evoked saliva from both parotid and submandibular glands were investigated. Clonidine at 1 mg/kg/day for 5 or 7 days caused a significant reduction in the salivary secretion (flow rate and total volume) evoked by parasympathetic nerve stimulation of parotid but not submandibular glands. Ion concentrations (Na, K and Ca) of parasympathetically nerve-evoked parotid saliva were not altered. However, the total protein concentration as well as output, amylase activity, and output of such saliva were markedly increased. Possible mechanisms for clonidine-induced increase in nerve-elicited salivary protein concentration include release of neuropeptides, and changes in adrenergic receptor binding which need further study.", "contents": "Effects of chronic clonidine administration on parasympathetic-evoked rat saliva. Effects of chronic administration of clonidine on parasympathetic-evoked saliva from both parotid and submandibular glands were investigated. Clonidine at 1 mg/kg/day for 5 or 7 days caused a significant reduction in the salivary secretion (flow rate and total volume) evoked by parasympathetic nerve stimulation of parotid but not submandibular glands. Ion concentrations (Na, K and Ca) of parasympathetically nerve-evoked parotid saliva were not altered. However, the total protein concentration as well as output, amylase activity, and output of such saliva were markedly increased. Possible mechanisms for clonidine-induced increase in nerve-elicited salivary protein concentration include release of neuropeptides, and changes in adrenergic receptor binding which need further study."} {"id": "PMID:1279338", "title": "Antiallergic mechanisms of beta-adrenergic stimulants in rats.", "content": "Antiallergic mechanisms of beta-adrenergic stimulants were investigated in rats. Isoproterenol administered intravenously inhibited IgE antibody-mediated homologous passive cutaneous anaphylaxis (PCA) and histamine-induced cutaneous reaction (HCR) elicited at the same time in the same rats significantly. The inhibition of PCA was more potent than that of HCR, suggesting that PCA is inhibited by at least 2 mechanisms. One is the inhibition of vascular permeability increase. In vivo histamine release in the rat peritoneal cavity caused by intravenous antigen was inhibited by the intravenous administration of isoproterenol or salbutamol dose-dependently. On the contrary, when the histamine release in the peritoneal cavity was caused by intraperitoneal antigen, isoproterenol or salbutamol administered simultaneously with antigen failed to inhibit the reaction. Furthermore, antigen-induced histamine release from sensitized peritoneal exudate cells in vitro was not inhibited by isoproterenol or salbutamol. These results indicate that the primary target of beta-adrenergic stimulants is the vascular endothelium, and that the direct inhibition of chemical mediator release from mast cells does not play an important role for the inhibition of PCA and in vivo histamine release in the peritoneal cavity in rats. Beta-adrenergic stimulants therefore may prevent intravenously administered antigen from activating sensitized mast cells through affecting endothelial cells.", "contents": "Antiallergic mechanisms of beta-adrenergic stimulants in rats. Antiallergic mechanisms of beta-adrenergic stimulants were investigated in rats. Isoproterenol administered intravenously inhibited IgE antibody-mediated homologous passive cutaneous anaphylaxis (PCA) and histamine-induced cutaneous reaction (HCR) elicited at the same time in the same rats significantly. The inhibition of PCA was more potent than that of HCR, suggesting that PCA is inhibited by at least 2 mechanisms. One is the inhibition of vascular permeability increase. In vivo histamine release in the rat peritoneal cavity caused by intravenous antigen was inhibited by the intravenous administration of isoproterenol or salbutamol dose-dependently. On the contrary, when the histamine release in the peritoneal cavity was caused by intraperitoneal antigen, isoproterenol or salbutamol administered simultaneously with antigen failed to inhibit the reaction. Furthermore, antigen-induced histamine release from sensitized peritoneal exudate cells in vitro was not inhibited by isoproterenol or salbutamol. These results indicate that the primary target of beta-adrenergic stimulants is the vascular endothelium, and that the direct inhibition of chemical mediator release from mast cells does not play an important role for the inhibition of PCA and in vivo histamine release in the peritoneal cavity in rats. Beta-adrenergic stimulants therefore may prevent intravenously administered antigen from activating sensitized mast cells through affecting endothelial cells."} {"id": "PMID:1279339", "title": "Dynamics of cyclic-AMP efflux in relation to alpha-MSH secretion from melanotrope cells of Xenopus laevis.", "content": "An important factor in regulating secretion from endocrine cells is the cytoplasmic concentration of cyclic-AMP. Many regulatory substances are known to either stimulate or inhibit the production of this second messenger through activation of their receptors. In the present study, we have monitored changes in cyclic-AMP efflux from melanotrope cells of Xenopus laevis in response to established neurochemical regulators of alpha-MSH secretion. In vitro superfusion of neurointermediate lobes allows for a dynamic recording of cyclic-AMP production in relation to hormone secretion. Unlike alpha-MSH secretion, the efflux of cyclic-AMP was not dependent on the concentration of extracellular calcium, indicating that hormone release and cyclic-AMP efflux are mediated by different mechanisms. The phosphodiesterase inhibitor IBMX and the adenylate cyclase activator forskolin stimulated cyclic-AMP efflux, but had no stimulatory effect on alpha-MSH release. This indicates that an increase in cyclic-AMP production in melanotrope cells is not necessarily accompanied by an increase in the rate of alpha-MSH release. Corticotropin-releasing factor stimulated cyclic-AMP efflux with dynamics similar to that induced by the amphibian peptide sauvagine. Dopamine and the GABAB receptor agonist baclofen both inhibited cyclic-AMP efflux and alpha-MSH release, with similar dynamics of inhibition and similar dose-response relationships. It is proposed that an inhibition of cyclic-AMP efflux is coupled to an inhibition of alpha-MSH secretion.", "contents": "Dynamics of cyclic-AMP efflux in relation to alpha-MSH secretion from melanotrope cells of Xenopus laevis. An important factor in regulating secretion from endocrine cells is the cytoplasmic concentration of cyclic-AMP. Many regulatory substances are known to either stimulate or inhibit the production of this second messenger through activation of their receptors. In the present study, we have monitored changes in cyclic-AMP efflux from melanotrope cells of Xenopus laevis in response to established neurochemical regulators of alpha-MSH secretion. In vitro superfusion of neurointermediate lobes allows for a dynamic recording of cyclic-AMP production in relation to hormone secretion. Unlike alpha-MSH secretion, the efflux of cyclic-AMP was not dependent on the concentration of extracellular calcium, indicating that hormone release and cyclic-AMP efflux are mediated by different mechanisms. The phosphodiesterase inhibitor IBMX and the adenylate cyclase activator forskolin stimulated cyclic-AMP efflux, but had no stimulatory effect on alpha-MSH release. This indicates that an increase in cyclic-AMP production in melanotrope cells is not necessarily accompanied by an increase in the rate of alpha-MSH release. Corticotropin-releasing factor stimulated cyclic-AMP efflux with dynamics similar to that induced by the amphibian peptide sauvagine. Dopamine and the GABAB receptor agonist baclofen both inhibited cyclic-AMP efflux and alpha-MSH release, with similar dynamics of inhibition and similar dose-response relationships. It is proposed that an inhibition of cyclic-AMP efflux is coupled to an inhibition of alpha-MSH secretion."} {"id": "PMID:1279340", "title": "Bee venom melittin is a potent toxin for reducing the threshold for calcium-induced calcium release in human and equine skeletal muscle.", "content": "The modulation of Ca2+ release by synthetic bee venom melittin was examined in equine and human terminal cisternae-containing fractions. Melittin (0.1 microM) decreased the threshold of Ca(2+)-induced Ca2+ release by 20% in equine muscle and by 36% in human muscle. If terminal cisternae fractions were first preloaded with Ca2+ to greater than about 75% of the threshold of Ca(2+)-induced Ca2+ release and then melittin added, an immediate and sustained release of Ca2+ occurred in preparations from both species. Addition of melittin after a Ca2+ preload of < 50% of the threshold of Ca(2+)-induced Ca2+ release did not elicit sustained Ca2+ release. Ruthenium red (10 microM) antagonized all effects of melittin on Ca2+ release. Melittin (0.1-10 microM) did not affect [3H]ryanodine binding. Melittin (0.1 microM) slightly (10%) inhibited the Ca2+ pump and this action was not antagonized by ruthenium red. These findings suggest that melittin may be an important new probe of the Ca(2+)-modulated Ca2+ release process that does not act at the ryanodine binding site.", "contents": "Bee venom melittin is a potent toxin for reducing the threshold for calcium-induced calcium release in human and equine skeletal muscle. The modulation of Ca2+ release by synthetic bee venom melittin was examined in equine and human terminal cisternae-containing fractions. Melittin (0.1 microM) decreased the threshold of Ca(2+)-induced Ca2+ release by 20% in equine muscle and by 36% in human muscle. If terminal cisternae fractions were first preloaded with Ca2+ to greater than about 75% of the threshold of Ca(2+)-induced Ca2+ release and then melittin added, an immediate and sustained release of Ca2+ occurred in preparations from both species. Addition of melittin after a Ca2+ preload of < 50% of the threshold of Ca(2+)-induced Ca2+ release did not elicit sustained Ca2+ release. Ruthenium red (10 microM) antagonized all effects of melittin on Ca2+ release. Melittin (0.1-10 microM) did not affect [3H]ryanodine binding. Melittin (0.1 microM) slightly (10%) inhibited the Ca2+ pump and this action was not antagonized by ruthenium red. These findings suggest that melittin may be an important new probe of the Ca(2+)-modulated Ca2+ release process that does not act at the ryanodine binding site."} {"id": "PMID:1279341", "title": "Developmental profile of polyadenylated and non-polyadenylated GABAA receptor subunit mRNAs.", "content": "The ratio of mRNA not selected for polyadenylation (non-poly(A)+ selected) to mRNA selected for polyadenylation (poly(A)+) for the beta 1, alpha 1 and gamma 2 subunits of the GABAA receptor complex was examined in rats as a function of age. RNA was extracted from whole brain of rats that were either 0, 1, 3, 5 or over 60 days of postnatal age. Poly(A)+ mRNA was purified by oligo(dT)-cellulose chromatography. Non-poly(A)+ selected mRNA and poly(A)+ mRNA for the GABAA receptor beta 1, alpha 1 and gamma 2 subunits were examined by Northern blot analysis using cDNA probes specific for these subunits. Levels of GABAA receptor beta 1 subunit mRNA were also examined by solution hybridization analysis with a beta 1 riboprobe. Analysis of Northern blots revealed that levels of poly(A)+ beta 1 subunit mRNA were highest at 0 days of age, but decreased and reached adult levels by 5 days of postnatal age. However, levels of the beta 1 subunit message extracted from non-poly(A)+ selected mRNA were not significantly different at any of the ages examined, suggesting the existence of a population of beta 1 subunit mRNA that is not polyadenylated. The age-related discrepancy between beta 1 subunit levels measured in non-poly(A)+ selected mRNA and poly(A)+ mRNA was also observed using solution hybridization analysis. In contrast, levels of both non-poly(A)+ selected mRNA and poly(A)+ mRNA for the alpha 1 subunit of the GABAA complex increased from 0 days of age to adulthood. Similarly, levels of both non-poly(A)+ selected mRNA and poly(A)+ mRNA for the GABAA receptor gamma 2 subunit increased with age.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Developmental profile of polyadenylated and non-polyadenylated GABAA receptor subunit mRNAs. The ratio of mRNA not selected for polyadenylation (non-poly(A)+ selected) to mRNA selected for polyadenylation (poly(A)+) for the beta 1, alpha 1 and gamma 2 subunits of the GABAA receptor complex was examined in rats as a function of age. RNA was extracted from whole brain of rats that were either 0, 1, 3, 5 or over 60 days of postnatal age. Poly(A)+ mRNA was purified by oligo(dT)-cellulose chromatography. Non-poly(A)+ selected mRNA and poly(A)+ mRNA for the GABAA receptor beta 1, alpha 1 and gamma 2 subunits were examined by Northern blot analysis using cDNA probes specific for these subunits. Levels of GABAA receptor beta 1 subunit mRNA were also examined by solution hybridization analysis with a beta 1 riboprobe. Analysis of Northern blots revealed that levels of poly(A)+ beta 1 subunit mRNA were highest at 0 days of age, but decreased and reached adult levels by 5 days of postnatal age. However, levels of the beta 1 subunit message extracted from non-poly(A)+ selected mRNA were not significantly different at any of the ages examined, suggesting the existence of a population of beta 1 subunit mRNA that is not polyadenylated. The age-related discrepancy between beta 1 subunit levels measured in non-poly(A)+ selected mRNA and poly(A)+ mRNA was also observed using solution hybridization analysis. In contrast, levels of both non-poly(A)+ selected mRNA and poly(A)+ mRNA for the alpha 1 subunit of the GABAA complex increased from 0 days of age to adulthood. Similarly, levels of both non-poly(A)+ selected mRNA and poly(A)+ mRNA for the GABAA receptor gamma 2 subunit increased with age.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279342", "title": "Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum.", "content": "A cDNA fragment homologous to other G protein-coupled receptors was isolated from rat brain using the PCR method and demonstrated to be abundantly expressed in striatum. Using this fragment as a probe, a 2.1 kb full-length cDNA was isolated from a rat striatal cDNA library. This cDNA encodes a protein of 410 amino acids and is highly homologous to previously isolated adenosine receptor cDNAs. Expression of this cDNA in COS cells revealed high affinity (Kd = 38.6 nM) and saturable binding of the A2 adenosine receptor-selective ligand [3H]CGS 21680. Agonist displacement profile of [3H]CGS 21680 binding was consistent with an adenosine receptor of the A2 subtype (NECA greater than (R)-PIA greater than CPA greater than (S)-PIA). In situ hybridization demonstrated that rat A2 adenosine receptor mRNA was co-expressed in the same striatal neurons as D2 dopamine receptor mRNA, and never co-expressed with striatal D1 dopamine receptor mRNA. Several lines of evidence have previously suggested that dopamine-induced changes in motor behavior can be modulated by adenosine analogs acting at the A2 subtype of adenosine receptor in the forebrain. The co-expression of D2 dopamine and A2 adenosine receptors in a subset of striatal cells provides an anatomical basis for dopaminergic-adenosinergic interactions on motor behavior.", "contents": "Molecular cloning of the rat A2 adenosine receptor: selective co-expression with D2 dopamine receptors in rat striatum. A cDNA fragment homologous to other G protein-coupled receptors was isolated from rat brain using the PCR method and demonstrated to be abundantly expressed in striatum. Using this fragment as a probe, a 2.1 kb full-length cDNA was isolated from a rat striatal cDNA library. This cDNA encodes a protein of 410 amino acids and is highly homologous to previously isolated adenosine receptor cDNAs. Expression of this cDNA in COS cells revealed high affinity (Kd = 38.6 nM) and saturable binding of the A2 adenosine receptor-selective ligand [3H]CGS 21680. Agonist displacement profile of [3H]CGS 21680 binding was consistent with an adenosine receptor of the A2 subtype (NECA greater than (R)-PIA greater than CPA greater than (S)-PIA). In situ hybridization demonstrated that rat A2 adenosine receptor mRNA was co-expressed in the same striatal neurons as D2 dopamine receptor mRNA, and never co-expressed with striatal D1 dopamine receptor mRNA. Several lines of evidence have previously suggested that dopamine-induced changes in motor behavior can be modulated by adenosine analogs acting at the A2 subtype of adenosine receptor in the forebrain. The co-expression of D2 dopamine and A2 adenosine receptors in a subset of striatal cells provides an anatomical basis for dopaminergic-adenosinergic interactions on motor behavior."} {"id": "PMID:1279343", "title": "Quantitation of preproenkephalin mRNA levels in brain regions from male Fischer rats following chronic cocaine treatment using a recently developed solution hybridization assay.", "content": "Quantitative solution hybridization assays were used to determine the picogram amounts of preproenkephalin mRNA (PPenk mRNA) and the microgram quanities of total rat RNA in extracts of eight brain regions from rats which had received three daily intraperitoneal injections of cocaine (10 or 30 mg/kg/day) or saline for 14 days. The young adult male Fischer rats were sacrificed 30 min after the final injection. The highest density of PPenk mRNA (pg PPenk mRNA/micrograms total cellular RNA) was found in extracts of striatum (34.08 +/- 1.79 pg/micrograms for 11 saline-treated rats), followed by extracts of nucleus accumbens (10.08 +/- 0.81 pg/micrograms), and extracts of hypothalamus (2.99 +/- 0.31 pg/micrograms). Extracts of frontal cortex (1.78 +/- 0.24 pg/micrograms), pituitary (1.39 +/- 0.08 pg/micrograms), central grey (1.31 +/- 0.16 pg/micrograms), and cerebellum (1.24 +/- 0.09 pg/micrograms) had intermediate values. Extracts of hippocampus (0.53 +/- 0.03 pg/micrograms) had the lowest density. No significant differences were found among the treatment groups in any brain area investigated. Therefore, chronic cocaine treatment as administered in this protocol did not alter expression of the gene encoding proenkephalin.", "contents": "Quantitation of preproenkephalin mRNA levels in brain regions from male Fischer rats following chronic cocaine treatment using a recently developed solution hybridization assay. Quantitative solution hybridization assays were used to determine the picogram amounts of preproenkephalin mRNA (PPenk mRNA) and the microgram quanities of total rat RNA in extracts of eight brain regions from rats which had received three daily intraperitoneal injections of cocaine (10 or 30 mg/kg/day) or saline for 14 days. The young adult male Fischer rats were sacrificed 30 min after the final injection. The highest density of PPenk mRNA (pg PPenk mRNA/micrograms total cellular RNA) was found in extracts of striatum (34.08 +/- 1.79 pg/micrograms for 11 saline-treated rats), followed by extracts of nucleus accumbens (10.08 +/- 0.81 pg/micrograms), and extracts of hypothalamus (2.99 +/- 0.31 pg/micrograms). Extracts of frontal cortex (1.78 +/- 0.24 pg/micrograms), pituitary (1.39 +/- 0.08 pg/micrograms), central grey (1.31 +/- 0.16 pg/micrograms), and cerebellum (1.24 +/- 0.09 pg/micrograms) had intermediate values. Extracts of hippocampus (0.53 +/- 0.03 pg/micrograms) had the lowest density. No significant differences were found among the treatment groups in any brain area investigated. Therefore, chronic cocaine treatment as administered in this protocol did not alter expression of the gene encoding proenkephalin."} {"id": "PMID:1279344", "title": "Preprogalanin mRNA is increased in vagal motor neurons following axotomy.", "content": "Expression of preprogalanin and tyrosine hydroxylase mRNA was examined in the rat dorsal vagal complex following nodose ganglionectomy and cervical vagotomy, using in situ hybridization of specific 35S-labelled oligonucleotides. Seven days after unilateral cervical vagotomy (and nodose ganglionectomy), neurons in the ipsilateral dorsal motor nucleus of the vagus and nucleus ambiguus expressed 6- to 10-fold increased levels of preprogalanin mRNA. In contrast, tyrosine hydroxylase mRNA was no longer expressed by cells of the dorsal motor nucleus of the vagus after the lesion. These results demonstrate that changes in the expression of the galanin and tyrosine hydroxylase genes occur in vagal motor neurons following lesion of their axons. More generally, these results, and those from other laboratories, demonstrate that specific alterations of neuropeptide and neurotransmitter production, are part of the reactive process activated by nerve injury.", "contents": "Preprogalanin mRNA is increased in vagal motor neurons following axotomy. Expression of preprogalanin and tyrosine hydroxylase mRNA was examined in the rat dorsal vagal complex following nodose ganglionectomy and cervical vagotomy, using in situ hybridization of specific 35S-labelled oligonucleotides. Seven days after unilateral cervical vagotomy (and nodose ganglionectomy), neurons in the ipsilateral dorsal motor nucleus of the vagus and nucleus ambiguus expressed 6- to 10-fold increased levels of preprogalanin mRNA. In contrast, tyrosine hydroxylase mRNA was no longer expressed by cells of the dorsal motor nucleus of the vagus after the lesion. These results demonstrate that changes in the expression of the galanin and tyrosine hydroxylase genes occur in vagal motor neurons following lesion of their axons. More generally, these results, and those from other laboratories, demonstrate that specific alterations of neuropeptide and neurotransmitter production, are part of the reactive process activated by nerve injury."} {"id": "PMID:1279345", "title": "Molecular cloning of a G-protein alpha i subunit from the lobster olfactory organ.", "content": "A G-protein alpha subunit was cloned from a lobster olfactory organ cDNA library and sequenced. The clone encodes an alpha i subunit based on the 80% identity its predicted amino acid sequence shares with mammalian alpha i subunits. On Northern blots of polyadenylated RNA, the clone hybridized to a 5 kb species from several tissues.", "contents": "Molecular cloning of a G-protein alpha i subunit from the lobster olfactory organ. A G-protein alpha subunit was cloned from a lobster olfactory organ cDNA library and sequenced. The clone encodes an alpha i subunit based on the 80% identity its predicted amino acid sequence shares with mammalian alpha i subunits. On Northern blots of polyadenylated RNA, the clone hybridized to a 5 kb species from several tissues."} {"id": "PMID:1279346", "title": "Expression of GAL mRNA in rat hypothalamus: effect of frontal deafferentation and colchicine treatment.", "content": "The expression of galanin (GAL) mRNA was determined by in situ hybridization after frontal deafferentation and colchicine treatment in the rat hypothalamus. Frontal deafferentation significantly increased the signal in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and dorsomedial nucleus (DMN). Colchicine treatment induced a diffuse enhancement of GAL mRNA in hypothalamic nuclei. When the two treatments were combined there was an additivity of GAL mRNA expression in the previous hypothalamic nuclei and also in the arcuate nucleus (AN), where the single treatments did not modify the signal. These results suggest the regulation of GAL mRNA expression mediated by a multineuronal pathway, separate from the colchicine-induced GAL mRNA increase.", "contents": "Expression of GAL mRNA in rat hypothalamus: effect of frontal deafferentation and colchicine treatment. The expression of galanin (GAL) mRNA was determined by in situ hybridization after frontal deafferentation and colchicine treatment in the rat hypothalamus. Frontal deafferentation significantly increased the signal in the paraventricular nucleus (PVN), the supraoptic nucleus (SON), and dorsomedial nucleus (DMN). Colchicine treatment induced a diffuse enhancement of GAL mRNA in hypothalamic nuclei. When the two treatments were combined there was an additivity of GAL mRNA expression in the previous hypothalamic nuclei and also in the arcuate nucleus (AN), where the single treatments did not modify the signal. These results suggest the regulation of GAL mRNA expression mediated by a multineuronal pathway, separate from the colchicine-induced GAL mRNA increase."} {"id": "PMID:1279347", "title": "Increase in galanin gene expression in locus coeruleus neurones of the rat following reserpine treatment.", "content": "Changes in galanin mRNA content in locus coeruleus neurones of the rat were studied after reserpine treatment (10 mg/kg s.c.) using an in situ hybridization technique and an alkaline phosphatase labelled oligodeoxynucleotide probe. An increase in galanin mRNA content in locus coeruleus neurones was detected as early as 3 h after reserpine treatment when compared to vehicle injected rats. A maximal increase in mRNA content was detected at 3 days after reserpine treatment. This transient increase in galanin mRNA content had subsided by post treatment day 20. The response of locus coeruleus neurones to the single reserpine injection was heterogeneous; cells in the dorsal portion of the nucleus exhibiting a greater response than ventrally located cells.", "contents": "Increase in galanin gene expression in locus coeruleus neurones of the rat following reserpine treatment. Changes in galanin mRNA content in locus coeruleus neurones of the rat were studied after reserpine treatment (10 mg/kg s.c.) using an in situ hybridization technique and an alkaline phosphatase labelled oligodeoxynucleotide probe. An increase in galanin mRNA content in locus coeruleus neurones was detected as early as 3 h after reserpine treatment when compared to vehicle injected rats. A maximal increase in mRNA content was detected at 3 days after reserpine treatment. This transient increase in galanin mRNA content had subsided by post treatment day 20. The response of locus coeruleus neurones to the single reserpine injection was heterogeneous; cells in the dorsal portion of the nucleus exhibiting a greater response than ventrally located cells."} {"id": "PMID:1279348", "title": "Sulfated glycoprotein-2 expression increases in rodent brain after transient global ischemia.", "content": "Sulfated glycoprotein-2 (SGP-2) is emerging as a prominent marker of neurodegeneration in mammalian brain. Regulation of brain SGP-2 was studied in adult male Wistar rats subjected to 30 min of forebrain ischemia by four vessel occlusion. By 3 days after the ischemic insult, SGP-2 RNA levels were increased two fold in caudate nucleus and hippocampus. SGP-2 protein levels assessed by immunoblots were markedly increased in both brain regions following ischemia. GFAP RNA levels also increased over 5 fold in caudate nucleus and hippocampus following the ischemic insult. Despite significant elevations in GFAP RNA, protein levels of GFAP assessed by immunoblot were only marginally affected. The elevated expression of SGP-2 in rodent brain following this and other experimental lesion paradigms (e.g., excitotoxic lesions, deafferentation) suggest some general involvement of SGP-2 in neurodegeneration and remodelling following neuronal injury.", "contents": "Sulfated glycoprotein-2 expression increases in rodent brain after transient global ischemia. Sulfated glycoprotein-2 (SGP-2) is emerging as a prominent marker of neurodegeneration in mammalian brain. Regulation of brain SGP-2 was studied in adult male Wistar rats subjected to 30 min of forebrain ischemia by four vessel occlusion. By 3 days after the ischemic insult, SGP-2 RNA levels were increased two fold in caudate nucleus and hippocampus. SGP-2 protein levels assessed by immunoblots were markedly increased in both brain regions following ischemia. GFAP RNA levels also increased over 5 fold in caudate nucleus and hippocampus following the ischemic insult. Despite significant elevations in GFAP RNA, protein levels of GFAP assessed by immunoblot were only marginally affected. The elevated expression of SGP-2 in rodent brain following this and other experimental lesion paradigms (e.g., excitotoxic lesions, deafferentation) suggest some general involvement of SGP-2 in neurodegeneration and remodelling following neuronal injury."} {"id": "PMID:1279349", "title": "Regulation of 2',3'-cyclic nucleotide phosphodiesterase gene expression in experimental peripheral neuropathies.", "content": "2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enzyme associated with central nervous system myelination. Although present in the mammalian peripheral nerve, it is not clear what its role is during myelination nor how the expression of this gene is regulated in the PNS. In this study, CNPase gene expression was studied in the crushed and permanently transected rat sciatic nerve, two models of peripheral nerve neuropathy. The Schwann cells of the crushed nerve initially demyelinate, remain in a non-myelinating condition until active regeneration induces remyelination (10-21 days after injury), whereas those of the permanently transected nerve remain in a quiescent, non-myelinating state after the initial demyelination. An increase of CNPase mRNA levels is observed during degeneration and remains high whether the peripheral nerve is regenerating or not, suggesting transcriptional activation of CNPase mRNA and/or increased CNPase mRNA stability as a response to nerve injury. In contrast, the steady state level of CNPase protein did not increase during degeneration or regeneration suggesting either negative translational regulation of CNPase gene expression or a higher turnover of this protein in the injured peripheral nerve. Furthermore, CNPase activity dropped sharply during early degeneration and remained low in the quiescent cells of the permanently transected nerve while it increased in the regenerating nerve. The results suggest that although transcriptional or post-transcriptional regulation of CNPase gene expression is not dependent on Schwann cell-axonal contact, the activity of CNPase appears to be dependent on myelination and indirectly dependent on the presence of axons in the peripheral nerve.", "contents": "Regulation of 2',3'-cyclic nucleotide phosphodiesterase gene expression in experimental peripheral neuropathies. 2',3'-Cyclic nucleotide 3'-phosphodiesterase (CNPase) is an enzyme associated with central nervous system myelination. Although present in the mammalian peripheral nerve, it is not clear what its role is during myelination nor how the expression of this gene is regulated in the PNS. In this study, CNPase gene expression was studied in the crushed and permanently transected rat sciatic nerve, two models of peripheral nerve neuropathy. The Schwann cells of the crushed nerve initially demyelinate, remain in a non-myelinating condition until active regeneration induces remyelination (10-21 days after injury), whereas those of the permanently transected nerve remain in a quiescent, non-myelinating state after the initial demyelination. An increase of CNPase mRNA levels is observed during degeneration and remains high whether the peripheral nerve is regenerating or not, suggesting transcriptional activation of CNPase mRNA and/or increased CNPase mRNA stability as a response to nerve injury. In contrast, the steady state level of CNPase protein did not increase during degeneration or regeneration suggesting either negative translational regulation of CNPase gene expression or a higher turnover of this protein in the injured peripheral nerve. Furthermore, CNPase activity dropped sharply during early degeneration and remained low in the quiescent cells of the permanently transected nerve while it increased in the regenerating nerve. The results suggest that although transcriptional or post-transcriptional regulation of CNPase gene expression is not dependent on Schwann cell-axonal contact, the activity of CNPase appears to be dependent on myelination and indirectly dependent on the presence of axons in the peripheral nerve."} {"id": "PMID:1279350", "title": "Expression of insulin-like growth factor-binding protein 2 (IGF-BP 2) following transient hypoxia-ischemia in the infant rat brain.", "content": "Hypoxia-ischemia induced by unilateral carotid ligation followed by either 15 (moderate) or 90 (severe) min exposure to 8% oxygen was associated with induction of IGF-BP 2 mRNA expression. A specific rat IGF-BP 2 cDNA probe was used to determine the IGF-BP 2 mRNA distribution in brain sections using in situ hybridization. Untreated control rats and the non-ligated hemisphere in experimental rats expressed IGF-BP 2 mRNA in the choroid plexus, meninges and more weakly in the thalamus, hippocampus and cortical layer 5. Increased expression in experimental rats was limited to regions known to have neuronal damage. Three days after the moderate insult the signal was increased in the CA1/2 region of the hippocampus and thalamus of the ligated side. Three days after the severe insult IGF-BP 2 expression was found surrounding the infarcted regions while by 5 days after severe insult the whole infarcted volume showed induction. The results suggest a role for the IGFs in the post-asphyxial response. IGF-BP 2 may alter the bio-availability of IGF 1 or 2 or modulate their actions in the area of infarction, and thus promote cerebral repair and recovery.", "contents": "Expression of insulin-like growth factor-binding protein 2 (IGF-BP 2) following transient hypoxia-ischemia in the infant rat brain. Hypoxia-ischemia induced by unilateral carotid ligation followed by either 15 (moderate) or 90 (severe) min exposure to 8% oxygen was associated with induction of IGF-BP 2 mRNA expression. A specific rat IGF-BP 2 cDNA probe was used to determine the IGF-BP 2 mRNA distribution in brain sections using in situ hybridization. Untreated control rats and the non-ligated hemisphere in experimental rats expressed IGF-BP 2 mRNA in the choroid plexus, meninges and more weakly in the thalamus, hippocampus and cortical layer 5. Increased expression in experimental rats was limited to regions known to have neuronal damage. Three days after the moderate insult the signal was increased in the CA1/2 region of the hippocampus and thalamus of the ligated side. Three days after the severe insult IGF-BP 2 expression was found surrounding the infarcted regions while by 5 days after severe insult the whole infarcted volume showed induction. The results suggest a role for the IGFs in the post-asphyxial response. IGF-BP 2 may alter the bio-availability of IGF 1 or 2 or modulate their actions in the area of infarction, and thus promote cerebral repair and recovery."} {"id": "PMID:1279351", "title": "Expression of human mid-sized neurofilament subunit in transgenic mice.", "content": "We have created transgenic mice which carry and express the gene encoding the human NF(M) subunit. RNAase protection assays reveal that the transgene is abundantly expressed in CNS and PNS but also, at very low levels in some non-neural tissues as well. Although the neurospecificity of transgene transcription was not absolute, we are able to detect the protein only in neurons with immunocytochemical techniques. Glial and endothelial cells do not contain immunoreactive materials. Interesting subtle differences in the relative level of the human transgene encoded and endogenous murine encoded NF(M) proteins were noted in different regions of the brain. Similar differences were found in the levels of transgene and endogenous gene mRNA suggesting that these differences may be traceable to differences in RNA transcription or stability. Our data demonstrate, within the sensitivity of the immunocytochemical techniques we used, that the human NF(M) protein is present only in the neurons of the transgenic mice and that it is present in the same neurons as the endogenous NF(M). Furthermore, immunoelectron-microscopic examination of isolated neurofilaments shows that the human NF(M) coassembles with the endogenous NF(M) during filament formation. Thus, although the human NF(M) possesses a much larger multiphosphorylation site in its carboxy terminus, it seems to be the functionally equivalent to the mouse protein, even in the murine neuron.", "contents": "Expression of human mid-sized neurofilament subunit in transgenic mice. We have created transgenic mice which carry and express the gene encoding the human NF(M) subunit. RNAase protection assays reveal that the transgene is abundantly expressed in CNS and PNS but also, at very low levels in some non-neural tissues as well. Although the neurospecificity of transgene transcription was not absolute, we are able to detect the protein only in neurons with immunocytochemical techniques. Glial and endothelial cells do not contain immunoreactive materials. Interesting subtle differences in the relative level of the human transgene encoded and endogenous murine encoded NF(M) proteins were noted in different regions of the brain. Similar differences were found in the levels of transgene and endogenous gene mRNA suggesting that these differences may be traceable to differences in RNA transcription or stability. Our data demonstrate, within the sensitivity of the immunocytochemical techniques we used, that the human NF(M) protein is present only in the neurons of the transgenic mice and that it is present in the same neurons as the endogenous NF(M). Furthermore, immunoelectron-microscopic examination of isolated neurofilaments shows that the human NF(M) coassembles with the endogenous NF(M) during filament formation. Thus, although the human NF(M) possesses a much larger multiphosphorylation site in its carboxy terminus, it seems to be the functionally equivalent to the mouse protein, even in the murine neuron."} {"id": "PMID:1279352", "title": "Novel DNA binding proteins participate in the regulation of human neurofilament H gene expression.", "content": "By a combination of DNase I footprinting, methylation interference, and gel shift analyses we have identified multiple binding sites for nuclear proteins within the promoter region of the human neurofilament H gene. Two sites likely bind the transcription factor Sp1 while two others may be targets for previously unrecognized DNA binding proteins. One site, PAL, occurs within the 10 bp sequence GGGGAGGAGG. Two copies of the PAL sequence form an interrupted palindrome around one of the Sp1 sites. A second site, PROX, is found within the sequence GGTTGGACC. Nuclear extracts prepared from both neural and non-neural cell lines, mouse brain, and mouse liver contain proteins that recognize and bind to the PROX and PAL sequences indicating that proteins which bind to these target sequences are widespread. The appearance of these target sequences in the 5' upstream region of several neuron specific genes suggests that they play key roles in the transcription of neuron specific genes. The functional activity of these target DNA sequences was demonstrated by transfection assays using a reporter gene fused to nested deletions of the NF(H) promoter region. Interestingly, these assays revealed that maximal transient expression was obtained with DNA fusion genes containing the PAL, PROX and TATA sequences. Inclusion of the Sp1 sites into the fusion genes failed to enhance the expression of the reporter gene. To determine if the NF(H) promoter can be activated in a tissue specific manner during development transgenic mice containing the promoter region linked to a beta-galactosidase reporter gene were generated. In one line sporadic expression of the transgene occurred in the CNS and testis while in four other lines no expression occurred. Collectively these results suggest that the NF(H) gene promoter is active in a tissue specific manner only by interactions with regulatory elements that lie further upstream or downstream of the start site of initiation.", "contents": "Novel DNA binding proteins participate in the regulation of human neurofilament H gene expression. By a combination of DNase I footprinting, methylation interference, and gel shift analyses we have identified multiple binding sites for nuclear proteins within the promoter region of the human neurofilament H gene. Two sites likely bind the transcription factor Sp1 while two others may be targets for previously unrecognized DNA binding proteins. One site, PAL, occurs within the 10 bp sequence GGGGAGGAGG. Two copies of the PAL sequence form an interrupted palindrome around one of the Sp1 sites. A second site, PROX, is found within the sequence GGTTGGACC. Nuclear extracts prepared from both neural and non-neural cell lines, mouse brain, and mouse liver contain proteins that recognize and bind to the PROX and PAL sequences indicating that proteins which bind to these target sequences are widespread. The appearance of these target sequences in the 5' upstream region of several neuron specific genes suggests that they play key roles in the transcription of neuron specific genes. The functional activity of these target DNA sequences was demonstrated by transfection assays using a reporter gene fused to nested deletions of the NF(H) promoter region. Interestingly, these assays revealed that maximal transient expression was obtained with DNA fusion genes containing the PAL, PROX and TATA sequences. Inclusion of the Sp1 sites into the fusion genes failed to enhance the expression of the reporter gene. To determine if the NF(H) promoter can be activated in a tissue specific manner during development transgenic mice containing the promoter region linked to a beta-galactosidase reporter gene were generated. In one line sporadic expression of the transgene occurred in the CNS and testis while in four other lines no expression occurred. Collectively these results suggest that the NF(H) gene promoter is active in a tissue specific manner only by interactions with regulatory elements that lie further upstream or downstream of the start site of initiation."} {"id": "PMID:1279353", "title": "Expression of tyrosine hydroxylase in cerebellar Purkinje neurons of the mutant tottering and leaner mouse.", "content": "In situ hybridization histochemistry, Northern blot analysis and immunohistochemistry were used to examine tyrosine hydroxylase (TH) mRNA concentrations and immunoreactivity in the locus coeruleus and cerebellum of the tottering (tg/tg), leaner (tgla/tgla), compound heterozygous (tg/tgla) and wild type control (+/+) mice, bred on a C57BL/6J background. Cerebellar Purkinje neurons, long considered to be GABAergic, showed high levels of TH mRNA in the caudal vermis and the lateral hemispheres of the cerebellum of tg/tg, tg/tgla, and tgla/tgla mice. Analysis of grain density over individual Purkinje cells showed significantly greater concentrations of TH mRNA in tg/tg, tg/tgla, and tgla/tgla mice as compared to +/+ wild type control mice. Comparison of adult (greater than or equal to 2 months) and young, pre-seizure (less than or equal to 3 weeks) mutant mice showed Purkinje cells densely labelled for TH mRNA at both ages, suggesting that TH gene expression in Purkinje cells is independent of the onset of seizures. Northern blot analysis confirmed the findings from the in situ hybridization studies, demonstrating a single band identical to TH mRNA. Immunohistochemistry confirmed the presence of TH protein in Purkinje cells of the caudal vermis and the lateral hemispheres of the cerebellum in both control and mutant mice. Quantitation of mRNA for TH and the coexisting neuropeptide, galanin, in the locus coeruleus detected no significant differences between adult tg/tg, tg/tgla and +/+ control mice. The present findings demonstrate that the classically GABAergic Purkinje cells in the cerebellum express low levels of TH, and that the mutant tottering and leaner strains of mice express extremely high levels of mRNA and protein for TH.", "contents": "Expression of tyrosine hydroxylase in cerebellar Purkinje neurons of the mutant tottering and leaner mouse. In situ hybridization histochemistry, Northern blot analysis and immunohistochemistry were used to examine tyrosine hydroxylase (TH) mRNA concentrations and immunoreactivity in the locus coeruleus and cerebellum of the tottering (tg/tg), leaner (tgla/tgla), compound heterozygous (tg/tgla) and wild type control (+/+) mice, bred on a C57BL/6J background. Cerebellar Purkinje neurons, long considered to be GABAergic, showed high levels of TH mRNA in the caudal vermis and the lateral hemispheres of the cerebellum of tg/tg, tg/tgla, and tgla/tgla mice. Analysis of grain density over individual Purkinje cells showed significantly greater concentrations of TH mRNA in tg/tg, tg/tgla, and tgla/tgla mice as compared to +/+ wild type control mice. Comparison of adult (greater than or equal to 2 months) and young, pre-seizure (less than or equal to 3 weeks) mutant mice showed Purkinje cells densely labelled for TH mRNA at both ages, suggesting that TH gene expression in Purkinje cells is independent of the onset of seizures. Northern blot analysis confirmed the findings from the in situ hybridization studies, demonstrating a single band identical to TH mRNA. Immunohistochemistry confirmed the presence of TH protein in Purkinje cells of the caudal vermis and the lateral hemispheres of the cerebellum in both control and mutant mice. Quantitation of mRNA for TH and the coexisting neuropeptide, galanin, in the locus coeruleus detected no significant differences between adult tg/tg, tg/tgla and +/+ control mice. The present findings demonstrate that the classically GABAergic Purkinje cells in the cerebellum express low levels of TH, and that the mutant tottering and leaner strains of mice express extremely high levels of mRNA and protein for TH."} {"id": "PMID:1279354", "title": "Ion channels in single bilayers induced by rat connexin32.", "content": "The gap junction channel mediates an important form of intercellular communication, but its detailed study is hindered by inaccessibility in situ. We show here that connexin32, the major protein composing junctional channels in rat liver, forms ion channels in single bilayer membranes. The properties of these reconstituted connexin32 channels are characterized and compared with those of gap junction channels. The demonstration that connexin32 forms channels in single membranes has implications for assembly and regulation of junctional channels, and permits detailed study of the gating, permeability and modulation of this channel-forming protein.", "contents": "Ion channels in single bilayers induced by rat connexin32. The gap junction channel mediates an important form of intercellular communication, but its detailed study is hindered by inaccessibility in situ. We show here that connexin32, the major protein composing junctional channels in rat liver, forms ion channels in single bilayer membranes. The properties of these reconstituted connexin32 channels are characterized and compared with those of gap junction channels. The demonstration that connexin32 forms channels in single membranes has implications for assembly and regulation of junctional channels, and permits detailed study of the gating, permeability and modulation of this channel-forming protein."} {"id": "PMID:1279355", "title": "Expression of a glutamate-activated chloride current in Xenopus oocytes injected with Caenorhabditis elegans RNA: evidence for modulation by avermectin.", "content": "Membrane currents were recorded from Xenopus laevis oocytes injected with C. elegans poly(A)+ RNA. In such oocytes glutamate activated an inward membrane current that desensitized in the continued presence of glutamate. Glutamate-receptor agonists quisqualate, kainate, and N-methyl-D-aspartate were inactive. The reversal potential of the glutamate-sensitive current was -22 mV, and exhibited a strong dependence on external chloride with a 48 mV change for a 10-fold change in chloride. The chloride channel blockers flufenamate and picrotoxin inhibited the glutamate-sensitive current. Ibotenate, a structural analog of glutamate, also activated a picrotoxin-sensitive chloride current. Ibotenate was inactive when current was partially desensitized with glutamate, and the responses to low concentrations of glutamate and ibotenate were additive. The anthelmintic/insecticide compound avermectin directly activated the glutamate-sensitive current. In addition, avermectin increased the response to submaximal concentrations of glutamate, shifted the glutamate concentration-response curve to lower concentrations, and slowed the desensitization of glutamate-sensitive current. We propose that the glutamate-sensitive chloride current and the avermectin-sensitive chloride current are mediated via the same channel.", "contents": "Expression of a glutamate-activated chloride current in Xenopus oocytes injected with Caenorhabditis elegans RNA: evidence for modulation by avermectin. Membrane currents were recorded from Xenopus laevis oocytes injected with C. elegans poly(A)+ RNA. In such oocytes glutamate activated an inward membrane current that desensitized in the continued presence of glutamate. Glutamate-receptor agonists quisqualate, kainate, and N-methyl-D-aspartate were inactive. The reversal potential of the glutamate-sensitive current was -22 mV, and exhibited a strong dependence on external chloride with a 48 mV change for a 10-fold change in chloride. The chloride channel blockers flufenamate and picrotoxin inhibited the glutamate-sensitive current. Ibotenate, a structural analog of glutamate, also activated a picrotoxin-sensitive chloride current. Ibotenate was inactive when current was partially desensitized with glutamate, and the responses to low concentrations of glutamate and ibotenate were additive. The anthelmintic/insecticide compound avermectin directly activated the glutamate-sensitive current. In addition, avermectin increased the response to submaximal concentrations of glutamate, shifted the glutamate concentration-response curve to lower concentrations, and slowed the desensitization of glutamate-sensitive current. We propose that the glutamate-sensitive chloride current and the avermectin-sensitive chloride current are mediated via the same channel."} {"id": "PMID:1279356", "title": "Multiexponential proton relaxation processes of compartmentalized water in gels.", "content": "The proton relaxation times, T1 and T2, of water in Sephadex gels, exhibiting pores of varying size (i.e., with exclusion limits of molecular weight between 10(3) and 10(5)) and water contents in the range 30 to 70% (w/w, weight of water to total weight), were measured at 20 MHz in the temperature range 5 to 50 degrees C. Multiexponential analysis of the relaxation curves revealed the existence of two relaxation components in all gel systems. A component with long T1 and T2 (T1,1 and T2,1) is associated with a large water fraction alpha 1,1 and alpha 2,1 and a component with short T1 and T2 (T1,2 and T2,2) with a small water fraction alpha 1,2 and alpha 2,2. An analysis of the temperature behavior of the relaxation components gives insight into the relaxation mechanisms. The relaxation process in water, compartmentalized in the gel matrix, is mainly controlled by dipole-dipole interactions. In addition, proton exchange processes between hydration water and hydroxyl groups of the matrix chain contribute under specific conditions and lead to a dramatic enhancement of the relaxation rate. In particular, for gels with small pores and with low water content proton exchange is observed. Compartments of water in gels could be models for compartments of water in biological tissues.", "contents": "Multiexponential proton relaxation processes of compartmentalized water in gels. The proton relaxation times, T1 and T2, of water in Sephadex gels, exhibiting pores of varying size (i.e., with exclusion limits of molecular weight between 10(3) and 10(5)) and water contents in the range 30 to 70% (w/w, weight of water to total weight), were measured at 20 MHz in the temperature range 5 to 50 degrees C. Multiexponential analysis of the relaxation curves revealed the existence of two relaxation components in all gel systems. A component with long T1 and T2 (T1,1 and T2,1) is associated with a large water fraction alpha 1,1 and alpha 2,1 and a component with short T1 and T2 (T1,2 and T2,2) with a small water fraction alpha 1,2 and alpha 2,2. An analysis of the temperature behavior of the relaxation components gives insight into the relaxation mechanisms. The relaxation process in water, compartmentalized in the gel matrix, is mainly controlled by dipole-dipole interactions. In addition, proton exchange processes between hydration water and hydroxyl groups of the matrix chain contribute under specific conditions and lead to a dramatic enhancement of the relaxation rate. In particular, for gels with small pores and with low water content proton exchange is observed. Compartments of water in gels could be models for compartments of water in biological tissues."} {"id": "PMID:1279357", "title": "Hydrazine sulfate protection against endotoxin lethality: analysis of effects on expression of hepatic cytokine genes and an acute-phase gene.", "content": "Hydrazine sulfate (HS) pretreatment protects mice against the lethal effects of bacterial endotoxin lipopolysaccharide (LPS) through mechanisms yet to be established. The liver was examined as a model organ to determine HS effects on (a) LPS activation of leukocyte (Kupffer cell) interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) genes and (b) subsequent cytokine-mediated induction of the acute-phase response as measured by hepatic metallothionein (MT) gene expression. The utility of this model was documented by in situ hybridization which showed that acute induction by LPS of the IL-1 beta gene occurred in cells found in liver sinusoids, consistent with Kupffer cells, whereas induction of the MT gene occurred in hepatocytes. The cell specific expression of these genes was further verified by Northern blot hybridization to LPS-treated liver RNA which showed that the LPS-mediated increase in hepatic cytokine mRNA levels, unlike that of MT, was not prevented by D-galactosamine (D-GalN) treatment. Northern blot hybridization established that HS pretreatment did not block the acute induction of hepatic cytokine mRNAs (IL-1 beta and TNF-alpha) by LPS nor did it induce these cytokine mRNAs in the absence of LPS. Northern blot hybridization further established that HS did not prevent LPS-mediated activation of hepatocyte MT gene expression. Thus, HS does not prevent LPS from activating liver leukocytes. These results also suggest that HS pretreatment neither prevents the general release of cytokines from LPS activated leukocytes nor the general induction of acute-phase protein gene expression in hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Hydrazine sulfate protection against endotoxin lethality: analysis of effects on expression of hepatic cytokine genes and an acute-phase gene. Hydrazine sulfate (HS) pretreatment protects mice against the lethal effects of bacterial endotoxin lipopolysaccharide (LPS) through mechanisms yet to be established. The liver was examined as a model organ to determine HS effects on (a) LPS activation of leukocyte (Kupffer cell) interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) genes and (b) subsequent cytokine-mediated induction of the acute-phase response as measured by hepatic metallothionein (MT) gene expression. The utility of this model was documented by in situ hybridization which showed that acute induction by LPS of the IL-1 beta gene occurred in cells found in liver sinusoids, consistent with Kupffer cells, whereas induction of the MT gene occurred in hepatocytes. The cell specific expression of these genes was further verified by Northern blot hybridization to LPS-treated liver RNA which showed that the LPS-mediated increase in hepatic cytokine mRNA levels, unlike that of MT, was not prevented by D-galactosamine (D-GalN) treatment. Northern blot hybridization established that HS pretreatment did not block the acute induction of hepatic cytokine mRNAs (IL-1 beta and TNF-alpha) by LPS nor did it induce these cytokine mRNAs in the absence of LPS. Northern blot hybridization further established that HS did not prevent LPS-mediated activation of hepatocyte MT gene expression. Thus, HS does not prevent LPS from activating liver leukocytes. These results also suggest that HS pretreatment neither prevents the general release of cytokines from LPS activated leukocytes nor the general induction of acute-phase protein gene expression in hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279358", "title": "[Methods for the evaluation of the mutagenic and genotoxic properties of chemical compounds. III. The sister chromatid exchange test in vivo (an abbreviated method)].", "content": "The principle and experimental procedure of the in vivo sister chromatid exchange (SCE) test applied in the screening of chemical compounds for their mutagenic properties are presented. The objective of this assay is to evaluate the ability of a test chemical to induce SCE in bone marrow cells of laboratory rodents. Animals are exposed to test substances by appropriate means and are sacrificed at sequential intervals. Chromosome preparations from bone marrow cells of the exposed animals are stained and examined for the presence sister chromatid exchange. The criterion of mutagenic effect of the test chemical is the dose-related increase in SCE frequency and/or statistically significant and reproducible positive response (beyond the level of the control group) for at least one dose of the test chemical.", "contents": "[Methods for the evaluation of the mutagenic and genotoxic properties of chemical compounds. III. The sister chromatid exchange test in vivo (an abbreviated method)]. The principle and experimental procedure of the in vivo sister chromatid exchange (SCE) test applied in the screening of chemical compounds for their mutagenic properties are presented. The objective of this assay is to evaluate the ability of a test chemical to induce SCE in bone marrow cells of laboratory rodents. Animals are exposed to test substances by appropriate means and are sacrificed at sequential intervals. Chromosome preparations from bone marrow cells of the exposed animals are stained and examined for the presence sister chromatid exchange. The criterion of mutagenic effect of the test chemical is the dose-related increase in SCE frequency and/or statistically significant and reproducible positive response (beyond the level of the control group) for at least one dose of the test chemical."} {"id": "PMID:1279359", "title": "Perturbing highly conserved spatial relationships in the regulatory domain that controls inducible cat translation.", "content": "Chloramphenicol activates translation of cat-86 mRNA by stalling a ribosome in the leader of individual transcripts. Stalling triggers two sequential events: the destabilization of a region of secondary structure that sequesters the cat ribosome-binding site (RBS-C), and the initiation of cat translation. The site of drug-dependent ribosome stalling is dictated by the leader sequence, crb; crb causes a ribosome to stall with its aminoacyl site at leader codon 6. We demonstrate that induction requires the maintenance of a precise spatial relationship between crb and sequences within the left inverted repeat of the secondary structure. Therefore, destabilization of the secondary structure during chloramphenicol induction may result from the interaction of a stalled ribosome with a specific sequence in the secondary structure rather than from non-specific masking of RNA sequences. cat-86 regulation also depends on the distance that separates crb from RBS-C. This interval of 33 nucleotides was incrementally increased and decreased by mutations within a loop in the secondary structure. Shortening the distance between crb and RBS-C by three nucleotides reduced induction by half and a deletion of nine nucleotides abolished induction. Insertion mutations were without effect on induced expression but elevated basal expression. The results indicate that when the A site of a ribosome occupies leader codon 6 the secondary structure is destabilized and there is no interference with entry of a second ribosome at RBS-C. The data further demonstrate that when the A site of a ribosome in the leader is within 30 nucleotides of RBS-C, cat expression decreases. This decrease probably results from competition of the leader ribosome with the ribosome initiating cat translation. Our observations demonstrate that in wild-type cat-86 the distances between crb and the secondary structure, and between crb and RBS-C provide the precise spacing necessary to achieve three interdependent effects: the destabilization of the RNA secondary structure by a ribosome stalled at crb; a lack of competition between a ribosome stalled at crb and the initiating ribosome; and maintenance of a low, but measurable, basal level of cat expression. The spatial relationships identified as necessary for the regulation of cat-86 are conserved in the regulatory regions for five other inducible cat genes.", "contents": "Perturbing highly conserved spatial relationships in the regulatory domain that controls inducible cat translation. Chloramphenicol activates translation of cat-86 mRNA by stalling a ribosome in the leader of individual transcripts. Stalling triggers two sequential events: the destabilization of a region of secondary structure that sequesters the cat ribosome-binding site (RBS-C), and the initiation of cat translation. The site of drug-dependent ribosome stalling is dictated by the leader sequence, crb; crb causes a ribosome to stall with its aminoacyl site at leader codon 6. We demonstrate that induction requires the maintenance of a precise spatial relationship between crb and sequences within the left inverted repeat of the secondary structure. Therefore, destabilization of the secondary structure during chloramphenicol induction may result from the interaction of a stalled ribosome with a specific sequence in the secondary structure rather than from non-specific masking of RNA sequences. cat-86 regulation also depends on the distance that separates crb from RBS-C. This interval of 33 nucleotides was incrementally increased and decreased by mutations within a loop in the secondary structure. Shortening the distance between crb and RBS-C by three nucleotides reduced induction by half and a deletion of nine nucleotides abolished induction. Insertion mutations were without effect on induced expression but elevated basal expression. The results indicate that when the A site of a ribosome occupies leader codon 6 the secondary structure is destabilized and there is no interference with entry of a second ribosome at RBS-C. The data further demonstrate that when the A site of a ribosome in the leader is within 30 nucleotides of RBS-C, cat expression decreases. This decrease probably results from competition of the leader ribosome with the ribosome initiating cat translation. Our observations demonstrate that in wild-type cat-86 the distances between crb and the secondary structure, and between crb and RBS-C provide the precise spacing necessary to achieve three interdependent effects: the destabilization of the RNA secondary structure by a ribosome stalled at crb; a lack of competition between a ribosome stalled at crb and the initiating ribosome; and maintenance of a low, but measurable, basal level of cat expression. The spatial relationships identified as necessary for the regulation of cat-86 are conserved in the regulatory regions for five other inducible cat genes."} {"id": "PMID:1279360", "title": "An SOS-inducible defective retronphage (phi R86) in Escherichia coli strain B.", "content": "In Escherichia coli, RecA protein regulates the DNA damage-inducible survival-enhancing SOS response. Mutant allele recA730, which causes constitutive SOS expression, is lethal at high temperatures in B/r, a derivative of wild-type B, but not in K-12 or in certain B/r--K-12 hybrids. We present evidence that killing is due to SOS induction of a defective retronphage, phi R86, which is integrated into the B/r chromosome at 19 min, but is absent in K-12. phi R86 contains retron EC-86 which encodes reverse transcriptase and a small multicopy DNA-RNA complex, msDNA-RNA. Induction of phi R86 in recA730 B/r strains results in inhibition of host DNA replication before cell death. A retronphage 'killer' gene, ORF336, when overexpressed from a plasmid, causes similar effects without SOS induction. phi R86 is not detectably u.v.-inducible in recA+ strains.", "contents": "An SOS-inducible defective retronphage (phi R86) in Escherichia coli strain B. In Escherichia coli, RecA protein regulates the DNA damage-inducible survival-enhancing SOS response. Mutant allele recA730, which causes constitutive SOS expression, is lethal at high temperatures in B/r, a derivative of wild-type B, but not in K-12 or in certain B/r--K-12 hybrids. We present evidence that killing is due to SOS induction of a defective retronphage, phi R86, which is integrated into the B/r chromosome at 19 min, but is absent in K-12. phi R86 contains retron EC-86 which encodes reverse transcriptase and a small multicopy DNA-RNA complex, msDNA-RNA. Induction of phi R86 in recA730 B/r strains results in inhibition of host DNA replication before cell death. A retronphage 'killer' gene, ORF336, when overexpressed from a plasmid, causes similar effects without SOS induction. phi R86 is not detectably u.v.-inducible in recA+ strains."} {"id": "PMID:1279361", "title": "Separation of two lipopolysaccharide populations with different contents of O-antigen factor 122 in Salmonella enterica serovar typhimurium.", "content": "Lipopolysaccharide (LPS) extraction from smooth-type Salmonella enterica sv. Typhimurium was carried out with the modified phenol/chloroform/petroleum ether method (volume ratio 5:5:8). In this procedure, LPS was precipitated from 90% phenol sequentially with water and acetone to yield LPS-H2O (minute amounts) and LPS-Ac (major amounts), respectively. Chemical analyses of the LPS fractions revealed that in the O antigen of LPS-H2O position C4 of the D-galactose was extensively glucosylated, corresponding corresponding to the O-antigen factor 122. In LPS-Ac, this glucosylation was negligible. Inspection of the LPS fractions by sodium dodecyl sulphate/polyacrylamide gel electrophoresis and silver staining suggested that the glucosylation in LPS-H2O was present only in LPS species with a chain length higher than six repeating units.", "contents": "Separation of two lipopolysaccharide populations with different contents of O-antigen factor 122 in Salmonella enterica serovar typhimurium. Lipopolysaccharide (LPS) extraction from smooth-type Salmonella enterica sv. Typhimurium was carried out with the modified phenol/chloroform/petroleum ether method (volume ratio 5:5:8). In this procedure, LPS was precipitated from 90% phenol sequentially with water and acetone to yield LPS-H2O (minute amounts) and LPS-Ac (major amounts), respectively. Chemical analyses of the LPS fractions revealed that in the O antigen of LPS-H2O position C4 of the D-galactose was extensively glucosylated, corresponding corresponding to the O-antigen factor 122. In LPS-Ac, this glucosylation was negligible. Inspection of the LPS fractions by sodium dodecyl sulphate/polyacrylamide gel electrophoresis and silver staining suggested that the glucosylation in LPS-H2O was present only in LPS species with a chain length higher than six repeating units."} {"id": "PMID:1279362", "title": "Methisoprinol-effect on the replication cycle of human hepatitis A virus.", "content": "The antiviral activity of methisoprinol was investigated under different conditions using a strain of hepatitis A virus (HAV), that shows a strong cytopathic effect on the Frp/3 cell line 7-9 days post-infection. Treatment of Frp/3 at a dose range of 125-1200 micrograms/ml had no toxic effect and showed a dose dependent inhibition of the HAV replication cycle. At the methisoprinol dose of 500 micrograms/ml the cytopathic effect was completely abolished and HAV antigen production reduced by 50% as measured by indirect immunofluorescence (IIF) and commercial enzyme-linked assay (ELISA). The virus yield was virtually abolished at the highest dose employed (1000 micrograms/ml).", "contents": "Methisoprinol-effect on the replication cycle of human hepatitis A virus. The antiviral activity of methisoprinol was investigated under different conditions using a strain of hepatitis A virus (HAV), that shows a strong cytopathic effect on the Frp/3 cell line 7-9 days post-infection. Treatment of Frp/3 at a dose range of 125-1200 micrograms/ml had no toxic effect and showed a dose dependent inhibition of the HAV replication cycle. At the methisoprinol dose of 500 micrograms/ml the cytopathic effect was completely abolished and HAV antigen production reduced by 50% as measured by indirect immunofluorescence (IIF) and commercial enzyme-linked assay (ELISA). The virus yield was virtually abolished at the highest dose employed (1000 micrograms/ml)."} {"id": "PMID:1279363", "title": "Prevalence of hepatitis C virus antibodies in Sydney blood donors.", "content": "To determine the prevalence of hepatitis C virus (HCV) antibodies in the Sydney blood donor population. All blood donations collected from Red Cross blood donors in Sydney from February 1990 until April 1991 were tested for HCV antibodies. For those samples found reactive in an anti-HCV screening test, a confirmatory test was carried out for the presence of HCV antibodies and the alanine aminotransferase level was measured. The prevalence of repeated reactivity to the screening test was 0.45% among blood donations overall, and 1.02% in donors giving blood for the first time in the study period. The confirmatory test result was positive for 30.8% of donations found to be repeatedly reactive in the screening test. There was little change over the study period in the HCV antibody prevalence of donors giving blood for the first time, but there was a clear decrease in the prevalence among all donations. Prevalence in males was nearly twice the prevalence in females--a difference which was consistent across age groups. The highest prevalence in both sexes was in the age group 30-34 years. Among samples for which the screening test results was positive, there was a strong correlation between the reactivity recorded for the screening test and both the proportion found positive by the confirmatory test and the proportion with an elevated alanine aminotransferase level. The small proportion of blood donations found to be repeatedly reactive by anti-HCV screening and the relatively good correlation with the confirmatory test and liver function assay indicate that a policy of discarding these donations will decrease the risk of transfusion-transmitted HCV infection without materially affecting the supply of blood.", "contents": "Prevalence of hepatitis C virus antibodies in Sydney blood donors. To determine the prevalence of hepatitis C virus (HCV) antibodies in the Sydney blood donor population. All blood donations collected from Red Cross blood donors in Sydney from February 1990 until April 1991 were tested for HCV antibodies. For those samples found reactive in an anti-HCV screening test, a confirmatory test was carried out for the presence of HCV antibodies and the alanine aminotransferase level was measured. The prevalence of repeated reactivity to the screening test was 0.45% among blood donations overall, and 1.02% in donors giving blood for the first time in the study period. The confirmatory test result was positive for 30.8% of donations found to be repeatedly reactive in the screening test. There was little change over the study period in the HCV antibody prevalence of donors giving blood for the first time, but there was a clear decrease in the prevalence among all donations. Prevalence in males was nearly twice the prevalence in females--a difference which was consistent across age groups. The highest prevalence in both sexes was in the age group 30-34 years. Among samples for which the screening test results was positive, there was a strong correlation between the reactivity recorded for the screening test and both the proportion found positive by the confirmatory test and the proportion with an elevated alanine aminotransferase level. The small proportion of blood donations found to be repeatedly reactive by anti-HCV screening and the relatively good correlation with the confirmatory test and liver function assay indicate that a policy of discarding these donations will decrease the risk of transfusion-transmitted HCV infection without materially affecting the supply of blood."} {"id": "PMID:1279364", "title": "Risk factors for hepatitis C virus infection in blood donors: a case-control study.", "content": "To investigate risk factors for hepatitis C virus (HCV) infection in Sydney blood donors. Blood donors confirmed to be positive for HCV antibodies were compared with blood donors with a positive result of a screening assay, but whose HCV antibody status had not been confirmed. A questionnaire on sexual, parenteral and other potential risk factors was administered to both groups. Blood Transfusion Service in Sydney. The study enrolled 220 donors who had confirmed HCV infection, and 210 donors who did not. The relative risk associated with injecting drug use was 63 (95% confidence interval, 19-260) when comparison was made with all other donors. Among donors who did not report injecting drug use, a significant, independent increase in risk was found in association with having had a tattoo. Among donors who did not give a history of parenteral exposure, there was a significantly greater risk in people with more than one life-time sexual partner than in those with at most one partner. A history of injecting drug use was elicited as the most important risk factor in Sydney blood donors with antibodies to hepatitis C. Having had a tattoo, and an increased number of lifetime sexual partners were also independently associated with HCV infection.", "contents": "Risk factors for hepatitis C virus infection in blood donors: a case-control study. To investigate risk factors for hepatitis C virus (HCV) infection in Sydney blood donors. Blood donors confirmed to be positive for HCV antibodies were compared with blood donors with a positive result of a screening assay, but whose HCV antibody status had not been confirmed. A questionnaire on sexual, parenteral and other potential risk factors was administered to both groups. Blood Transfusion Service in Sydney. The study enrolled 220 donors who had confirmed HCV infection, and 210 donors who did not. The relative risk associated with injecting drug use was 63 (95% confidence interval, 19-260) when comparison was made with all other donors. Among donors who did not report injecting drug use, a significant, independent increase in risk was found in association with having had a tattoo. Among donors who did not give a history of parenteral exposure, there was a significantly greater risk in people with more than one life-time sexual partner than in those with at most one partner. A history of injecting drug use was elicited as the most important risk factor in Sydney blood donors with antibodies to hepatitis C. Having had a tattoo, and an increased number of lifetime sexual partners were also independently associated with HCV infection."} {"id": "PMID:1279365", "title": "Clinical assessment and incidence of hepatitis C RNA in 50 consecutive RIBA-positive volunteer blood donors.", "content": "(i) To assess evidence of liver disease in 50 consecutive volunteer blood donors who were anti-hepatitis C virus (anti-HCV) antibody positive and who were referred to one hepatologist; (ii) to assay for viral RNA in serum in these patients. Royal Prince Alfred Hospital, a teaching hospital of the University of Sydney. Fifty people who were detected by the NSW Red Cross Blood Transfusion Service to be anti-HCV antibody positive and to have a positive result on recombinant immunoblot assay (RIBA) were assessed by one hepatologist for symptoms, signs and biochemical evidence of hepatic dysfunction. These patients were consecutive referrals from this source. Sixteen of these patients also consented to liver biopsy assessment. All patients had serum assayed for viral RNA by polymerase chain reaction with a combination of 3' and 5' primers. The 50 blood donors consisted of 28 men and 22 women, with a mean age of 34.5 years. Forty-six patients were asymptomatic. Only six had a past history of hepatitis while 14 had minor signs of chronic liver disease. In 28, injecting drug use was thought the most likely source of exposure to HCV. The minimal mean time since exposure to HCV in these patients was 8.8 +/- 5.2 years. Eight patients had received a blood transfusion at a mean time of 15.0 +/- 9.8 years from the time of consultation. The mean maximum level of alanine aminotransferase (ALT) in all 50 patients was 102.8 U/L. Five patients had persistently normal ALT levels; another 22 had at least one normal ALT level. Liver biopsies indicated chronic persistent hepatitis in 11 patients, mild chronic active hepatitis in three patients and more severe chronic active hepatitis in one. One patient had cirrhosis on biopsy. Forty-two patients had viral RNA detected in serum. Chronic infection with HCV in blood donors was invariably asymptomatic; 78% of patients had no signs of chronic liver disease and 68% had a maximum hepatic transaminase level of less than 100 U/L. Although severe liver disease was seen in two of 16 biopsies, the majority of these patients have mild liver disease despite a mean of about 10 years since exposure to the virus. Eighty-four per cent of patients had evidence of viral RNA in serum.", "contents": "Clinical assessment and incidence of hepatitis C RNA in 50 consecutive RIBA-positive volunteer blood donors. (i) To assess evidence of liver disease in 50 consecutive volunteer blood donors who were anti-hepatitis C virus (anti-HCV) antibody positive and who were referred to one hepatologist; (ii) to assay for viral RNA in serum in these patients. Royal Prince Alfred Hospital, a teaching hospital of the University of Sydney. Fifty people who were detected by the NSW Red Cross Blood Transfusion Service to be anti-HCV antibody positive and to have a positive result on recombinant immunoblot assay (RIBA) were assessed by one hepatologist for symptoms, signs and biochemical evidence of hepatic dysfunction. These patients were consecutive referrals from this source. Sixteen of these patients also consented to liver biopsy assessment. All patients had serum assayed for viral RNA by polymerase chain reaction with a combination of 3' and 5' primers. The 50 blood donors consisted of 28 men and 22 women, with a mean age of 34.5 years. Forty-six patients were asymptomatic. Only six had a past history of hepatitis while 14 had minor signs of chronic liver disease. In 28, injecting drug use was thought the most likely source of exposure to HCV. The minimal mean time since exposure to HCV in these patients was 8.8 +/- 5.2 years. Eight patients had received a blood transfusion at a mean time of 15.0 +/- 9.8 years from the time of consultation. The mean maximum level of alanine aminotransferase (ALT) in all 50 patients was 102.8 U/L. Five patients had persistently normal ALT levels; another 22 had at least one normal ALT level. Liver biopsies indicated chronic persistent hepatitis in 11 patients, mild chronic active hepatitis in three patients and more severe chronic active hepatitis in one. One patient had cirrhosis on biopsy. Forty-two patients had viral RNA detected in serum. Chronic infection with HCV in blood donors was invariably asymptomatic; 78% of patients had no signs of chronic liver disease and 68% had a maximum hepatic transaminase level of less than 100 U/L. Although severe liver disease was seen in two of 16 biopsies, the majority of these patients have mild liver disease despite a mean of about 10 years since exposure to the virus. Eighty-four per cent of patients had evidence of viral RNA in serum."} {"id": "PMID:1279367", "title": "A case of human melioidosis originating in south-west Western Australia.", "content": "To report the first human case of autochthonous melioidosis in temperate Australia (latitude 31 degrees 10'S) and to describe the extent of the presence of the causative agent, Pseudomonas pseudomallei, in southwest Western Australia. A 45-year-old man living on a hobby farm was admitted to hospital for investigation of lung lesions, weight loss and low grade fevers. P. pseudomallei was cultured from material from an aspiration biopsy of a mediastinal mass. The patient was successfully treated with a regimen of ceftazidime and trimethoprim-sulfamethoxazole. A review of epidemiological data showed that, since 1967, P. pseudomallei has been cultured from animals and soil in a region 50-250 km north-west of Perth, Western Australia, and that pockets of endemicity are found in the districts of Toodyay (where our patient's farm was), Chittering, Ballidu, Gidgegannup, Badgingarra, and Wongan Hills. The persistence of the bacterium in animals and soil in south-west Western Australia demonstrates abundantly that P. pseudomallei can exist opportunely beyond its traditional tropical habitat. It is likely that there will be further clinical cases of melioidosis originating in this region, and that the boundaries of endemicity in Australia will expand further.", "contents": "A case of human melioidosis originating in south-west Western Australia. To report the first human case of autochthonous melioidosis in temperate Australia (latitude 31 degrees 10'S) and to describe the extent of the presence of the causative agent, Pseudomonas pseudomallei, in southwest Western Australia. A 45-year-old man living on a hobby farm was admitted to hospital for investigation of lung lesions, weight loss and low grade fevers. P. pseudomallei was cultured from material from an aspiration biopsy of a mediastinal mass. The patient was successfully treated with a regimen of ceftazidime and trimethoprim-sulfamethoxazole. A review of epidemiological data showed that, since 1967, P. pseudomallei has been cultured from animals and soil in a region 50-250 km north-west of Perth, Western Australia, and that pockets of endemicity are found in the districts of Toodyay (where our patient's farm was), Chittering, Ballidu, Gidgegannup, Badgingarra, and Wongan Hills. The persistence of the bacterium in animals and soil in south-west Western Australia demonstrates abundantly that P. pseudomallei can exist opportunely beyond its traditional tropical habitat. It is likely that there will be further clinical cases of melioidosis originating in this region, and that the boundaries of endemicity in Australia will expand further."} {"id": "PMID:1279368", "title": "Molecular analysis of the outer surface protein A (OspA) of Borrelia burgdorferi for conserved and variable antibody binding domains.", "content": "The outer surface protein A (OspA) of Borrelia burgdorferi is a major candidate for development of a borrelia vaccine. However, vaccine development may be aggravated by the immunological heterogeneity of OspA. In this respect the knowledge about conserved and variable epitopes is of major interest. In this study truncated proteins derived from two different OspA serotypes of B. burgdorferi were mapped for conserved and specific antibody-binding domains. The OspA fragments were reacted in the Western blot with eight different OspA-specific monoclonal antibodies recognizing between one and seven of the seven OspA serotypes previously described. The two broadly reacting antibodies (recognizing all serotypes) react with N-terminal fragments of 93 and 214 amino acids, respectively, whereas antibodies recognizing only one and two to four of the seven serotypes are reactive with C-terminal fragments of amino acid 143-273 and 109-273, respectively. Thus, conserved antibody-binding domains are located nearer to the N terminus than serotype-specific ones. Comparison of the results from western blot mapping with OspA sequence data suggested certain conserved or variable regions as probable candidates for antigenic sites involved in linear or conformationally dependent epitopes. This, however, needs to be confirmed by epitope mapping using the respective synthetic peptides.", "contents": "Molecular analysis of the outer surface protein A (OspA) of Borrelia burgdorferi for conserved and variable antibody binding domains. The outer surface protein A (OspA) of Borrelia burgdorferi is a major candidate for development of a borrelia vaccine. However, vaccine development may be aggravated by the immunological heterogeneity of OspA. In this respect the knowledge about conserved and variable epitopes is of major interest. In this study truncated proteins derived from two different OspA serotypes of B. burgdorferi were mapped for conserved and specific antibody-binding domains. The OspA fragments were reacted in the Western blot with eight different OspA-specific monoclonal antibodies recognizing between one and seven of the seven OspA serotypes previously described. The two broadly reacting antibodies (recognizing all serotypes) react with N-terminal fragments of 93 and 214 amino acids, respectively, whereas antibodies recognizing only one and two to four of the seven serotypes are reactive with C-terminal fragments of amino acid 143-273 and 109-273, respectively. Thus, conserved antibody-binding domains are located nearer to the N terminus than serotype-specific ones. Comparison of the results from western blot mapping with OspA sequence data suggested certain conserved or variable regions as probable candidates for antigenic sites involved in linear or conformationally dependent epitopes. This, however, needs to be confirmed by epitope mapping using the respective synthetic peptides."} {"id": "PMID:1279369", "title": "Determination of the minimal length of preS1 epitope recognized by a monoclonal antibody which inhibits attachment of hepatitis B virus to hepatocytes.", "content": "The minimal amino acid sequence sufficient to be recognized efficiently by virus-attachment inhibiting murine monoclonal anti-preS1 antibody MA18/7 has been determined. We have constructed a recombinant gene library using the cloned coat protein gene of Escherichia coli RNA bacteriophage fr as a carrier. Different fragments of preS1 region from cloned hepatitis B virus (HBV) genomes, subtype ayw and adw, were inserted at position 2 of the 129 amino acid-long fr coat protein gene in the appropriate E. coli expression vectors. Fine mapping of preS1 epitope recognized by MA18/7 was accomplished by bidirectional shortening of the preS1 within original recombinant preS-fr coat protein genes with Bal31 exonuclease. Immunoblot analysis of the obtained recombinant protein library revealed that the tetrapeptide Asp-Pro-Ala-Phe (DPAF), located at the position preS(31-34) and conserved in all known HBV genomes, is sufficient to bind MA18/7 antibody. Recognition of the preS1 region by MA18/7 occurred irrespective of the amino acid context surrounding this DPAF tetrapeptide. Further shortening of this minimal epitope from the left or from the right side completely prevented antibody binding in immunoblots.", "contents": "Determination of the minimal length of preS1 epitope recognized by a monoclonal antibody which inhibits attachment of hepatitis B virus to hepatocytes. The minimal amino acid sequence sufficient to be recognized efficiently by virus-attachment inhibiting murine monoclonal anti-preS1 antibody MA18/7 has been determined. We have constructed a recombinant gene library using the cloned coat protein gene of Escherichia coli RNA bacteriophage fr as a carrier. Different fragments of preS1 region from cloned hepatitis B virus (HBV) genomes, subtype ayw and adw, were inserted at position 2 of the 129 amino acid-long fr coat protein gene in the appropriate E. coli expression vectors. Fine mapping of preS1 epitope recognized by MA18/7 was accomplished by bidirectional shortening of the preS1 within original recombinant preS-fr coat protein genes with Bal31 exonuclease. Immunoblot analysis of the obtained recombinant protein library revealed that the tetrapeptide Asp-Pro-Ala-Phe (DPAF), located at the position preS(31-34) and conserved in all known HBV genomes, is sufficient to bind MA18/7 antibody. Recognition of the preS1 region by MA18/7 occurred irrespective of the amino acid context surrounding this DPAF tetrapeptide. Further shortening of this minimal epitope from the left or from the right side completely prevented antibody binding in immunoblots."} {"id": "PMID:1279370", "title": "Differential upregulation of PLP and MAG genes in C6 glioma cells by N2A neuroblastoma conditioned medium.", "content": "The effect of factors released from N2A neuroblastoma cells on the expression of myelin protein genes in glioma C6 cells, i.e., proteolipid protein (PLP) and myelin-associated glycoprotein (MAG), was studied. Both cells lines were propagated in serum-free DMEM-F10 (1:1) medium. The addition of 50% N2A conditioned medium (N2ACM) stimulated the proliferation of C6 cells by approximately 4.5 fold as compared to control cells. The N2ACM-treated cells formed aggregates indicating increased cell-cell affinity. The exposure of C6 cells to N2ACM transiently stimulated the expression of both the MAG-specific and the PLP-specific messages up to eight and four fold over the control values, respectively. The maximal upregulation of the PLP gene occurred two days after N2ACM administration and preceded that of the MAG gene by two days. The effect of N2ACM was dose-dependent in the range of 12.5 to 50%. The secretion of N2A paracrine factors that stimulated the myelin gene expression was also time-dependent. The optimal conditioning time for the release of the PLP gene-stimulating activity was one day, while the maximal MAG gene-stimulating activity was found in the medium conditioned for 3 days. This cellular system may provide a convenient model for studies on trophic neuronal-glial interaction. Furthermore, the results indicate a difference in the regulatory mechanisms between the PLP and the MAG genes.", "contents": "Differential upregulation of PLP and MAG genes in C6 glioma cells by N2A neuroblastoma conditioned medium. The effect of factors released from N2A neuroblastoma cells on the expression of myelin protein genes in glioma C6 cells, i.e., proteolipid protein (PLP) and myelin-associated glycoprotein (MAG), was studied. Both cells lines were propagated in serum-free DMEM-F10 (1:1) medium. The addition of 50% N2A conditioned medium (N2ACM) stimulated the proliferation of C6 cells by approximately 4.5 fold as compared to control cells. The N2ACM-treated cells formed aggregates indicating increased cell-cell affinity. The exposure of C6 cells to N2ACM transiently stimulated the expression of both the MAG-specific and the PLP-specific messages up to eight and four fold over the control values, respectively. The maximal upregulation of the PLP gene occurred two days after N2ACM administration and preceded that of the MAG gene by two days. The effect of N2ACM was dose-dependent in the range of 12.5 to 50%. The secretion of N2A paracrine factors that stimulated the myelin gene expression was also time-dependent. The optimal conditioning time for the release of the PLP gene-stimulating activity was one day, while the maximal MAG gene-stimulating activity was found in the medium conditioned for 3 days. This cellular system may provide a convenient model for studies on trophic neuronal-glial interaction. Furthermore, the results indicate a difference in the regulatory mechanisms between the PLP and the MAG genes."} {"id": "PMID:1279371", "title": "Ascorbic acid upregulates myelin gene expression in C6 glioma cells.", "content": "The effect of ascorbic acid (AA) on rat glioma C6 cells was studied. At physiological AA concentrations of 0.1 and 1 mM, no morphological and no proliferative alterations in the C6 cultures were detectable. Although the total RNA content per cell was not affected by the AA-treatment, AA upregulated the expression of myelin-specific genes, i.e. proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) genes as assessed by northern blot analysis. The steady-state level of the specific mRNAs increased transiently in the AA-treated cells. Three days after AA administration the message level reached a maximum of 10- and 2-fold over control for the PLP and MAG genes, respectively. The upregulation of the genes was directly related to AA concentration. The present data indicate a possible involvement of AA in the regulation of myelin gene activity in the CNS.", "contents": "Ascorbic acid upregulates myelin gene expression in C6 glioma cells. The effect of ascorbic acid (AA) on rat glioma C6 cells was studied. At physiological AA concentrations of 0.1 and 1 mM, no morphological and no proliferative alterations in the C6 cultures were detectable. Although the total RNA content per cell was not affected by the AA-treatment, AA upregulated the expression of myelin-specific genes, i.e. proteolipid protein (PLP) and myelin-associated glycoprotein (MAG) genes as assessed by northern blot analysis. The steady-state level of the specific mRNAs increased transiently in the AA-treated cells. Three days after AA administration the message level reached a maximum of 10- and 2-fold over control for the PLP and MAG genes, respectively. The upregulation of the genes was directly related to AA concentration. The present data indicate a possible involvement of AA in the regulation of myelin gene activity in the CNS."} {"id": "PMID:1279372", "title": "Unintentional deaths from carbon monoxide poisoning--Michigan, 1987-1989.", "content": "Deaths from unintentional carbon monoxide (CO) poisoning in the United States result primarily from exposure to motor-vehicle exhaust and occur more often during the cold months of the year and in northern and midwestern states (1-3). In Michigan, from 1987 through 1989, 103 deaths were related to unintentional CO poisoning. To identify approaches for prevention of unintentional CO poisoning in Michigan, the Michigan Council on Injury Control (MCIC) studied death records and medical examiner (ME) records to determine the manner of deaths related to unintentional CO poisoning in that state from 1987 through 1989. This report summarizes findings of the investigation.", "contents": "Unintentional deaths from carbon monoxide poisoning--Michigan, 1987-1989. Deaths from unintentional carbon monoxide (CO) poisoning in the United States result primarily from exposure to motor-vehicle exhaust and occur more often during the cold months of the year and in northern and midwestern states (1-3). In Michigan, from 1987 through 1989, 103 deaths were related to unintentional CO poisoning. To identify approaches for prevention of unintentional CO poisoning in Michigan, the Michigan Council on Injury Control (MCIC) studied death records and medical examiner (ME) records to determine the manner of deaths related to unintentional CO poisoning in that state from 1987 through 1989. This report summarizes findings of the investigation."} {"id": "PMID:1279373", "title": "[Postoperative hyperamylasemia in patients undergoing abdominal surgery: the relationship between serum and peritoneal amylase levels].", "content": "This study was undertaken to investigate the incidence of postoperative hyperamylasemia and amylase levels of intraperitoneal drainage in 106 patients undergoing major abdominal surgery. The results were as follows: 1. Postoperative hyperamylasemia was found in 36.8% of all patients, with higher incidence of hyperamylasemia being in accordance with greater surgical intervention to the pancreas. 2. The isoamylase pattern of postoperative hyperamylasemia was dominant in the salivary type. 3. The levels of such serum pancreatic enzymes as lipase, trypsin and elastase 1 were higher in the pancreatic-type group than in the salivary-type group, particularly with the elastase 1 levels being statistically higher in the former. 4. Increases in peritoneal amylase activity were found in those cases of greater surgical intervention to the pancreas, postoperative hyperamylasemia and higher serum pancreatic isoamylase levels. 5. Diagnosis of postoperative pancreatitis was confirmed in one case by clinical and laboratory findings and CT examination. It might be concluded that postoperative high peritoneal amylase levels suggest occurrence or possible occurrence of postoperative pancreatitis.", "contents": "[Postoperative hyperamylasemia in patients undergoing abdominal surgery: the relationship between serum and peritoneal amylase levels]. This study was undertaken to investigate the incidence of postoperative hyperamylasemia and amylase levels of intraperitoneal drainage in 106 patients undergoing major abdominal surgery. The results were as follows: 1. Postoperative hyperamylasemia was found in 36.8% of all patients, with higher incidence of hyperamylasemia being in accordance with greater surgical intervention to the pancreas. 2. The isoamylase pattern of postoperative hyperamylasemia was dominant in the salivary type. 3. The levels of such serum pancreatic enzymes as lipase, trypsin and elastase 1 were higher in the pancreatic-type group than in the salivary-type group, particularly with the elastase 1 levels being statistically higher in the former. 4. Increases in peritoneal amylase activity were found in those cases of greater surgical intervention to the pancreas, postoperative hyperamylasemia and higher serum pancreatic isoamylase levels. 5. Diagnosis of postoperative pancreatitis was confirmed in one case by clinical and laboratory findings and CT examination. It might be concluded that postoperative high peritoneal amylase levels suggest occurrence or possible occurrence of postoperative pancreatitis."} {"id": "PMID:1279374", "title": "Suppression of carboxy-terminal truncations of the yeast mitochondrial mRNA-specific translational activator PET122 by mutations in two new genes, MRP17 and PET127.", "content": "The PET122 protein is one of three Saccharomyces cerevisiae nuclear gene products required specifically to activate translation of the mitochondrially coded COX3 mRNA. We have previously observed that mutations which remove the carboxy-terminal region of PET122 block translation of the COX3 mRNA but can be suppressed by unlinked nuclear mutations in several genes, two of which have been shown to code for proteins of the small subunit of mitochondrial ribosomes. Here we describe and map two more new genes identified as allele-specific suppressors that compensate for carboxy-terminal truncation of PET122. One of these genes, MRP17, is essential for the expression of all mitochondrial genes and encodes a protein of M(r) 17343. The MRP17 protein is a component of the small ribosomal subunit in mitochondria, as demonstrated by the fact that a missense mutation, mrp17-1, predicted to cause a charge change indeed alters the charge of a mitochondrial ribosomal protein of the expected size. In addition, mrp17-1, in combination with some mutations affecting another mitochondrial ribosomal protein, caused a synthetic defective phenotype. These findings are consistent with a model in which PET122 functionally interacts with the ribosomal small subunit. The second new suppressor gene described here, PET127, encodes a protein too large (M(r) 95900) to be a ribosomal protein and appears to operate by a different mechanism. PET127 is not absolutely required for mitochondrial gene expression and allele-specific suppression of pet122 mutations results from the loss of PET127 function: a pet127 deletion exhibited the same recessive suppressor activity as the original suppressor mutation. These findings suggest the possibility that PET127 could be a novel component of the mitochondrial translation system with a role in promoting accuracy of translational initiation.", "contents": "Suppression of carboxy-terminal truncations of the yeast mitochondrial mRNA-specific translational activator PET122 by mutations in two new genes, MRP17 and PET127. The PET122 protein is one of three Saccharomyces cerevisiae nuclear gene products required specifically to activate translation of the mitochondrially coded COX3 mRNA. We have previously observed that mutations which remove the carboxy-terminal region of PET122 block translation of the COX3 mRNA but can be suppressed by unlinked nuclear mutations in several genes, two of which have been shown to code for proteins of the small subunit of mitochondrial ribosomes. Here we describe and map two more new genes identified as allele-specific suppressors that compensate for carboxy-terminal truncation of PET122. One of these genes, MRP17, is essential for the expression of all mitochondrial genes and encodes a protein of M(r) 17343. The MRP17 protein is a component of the small ribosomal subunit in mitochondria, as demonstrated by the fact that a missense mutation, mrp17-1, predicted to cause a charge change indeed alters the charge of a mitochondrial ribosomal protein of the expected size. In addition, mrp17-1, in combination with some mutations affecting another mitochondrial ribosomal protein, caused a synthetic defective phenotype. These findings are consistent with a model in which PET122 functionally interacts with the ribosomal small subunit. The second new suppressor gene described here, PET127, encodes a protein too large (M(r) 95900) to be a ribosomal protein and appears to operate by a different mechanism. PET127 is not absolutely required for mitochondrial gene expression and allele-specific suppression of pet122 mutations results from the loss of PET127 function: a pet127 deletion exhibited the same recessive suppressor activity as the original suppressor mutation. These findings suggest the possibility that PET127 could be a novel component of the mitochondrial translation system with a role in promoting accuracy of translational initiation."} {"id": "PMID:1279375", "title": "Characterization of the effects of a new Ca2+ channel activator, FPL 64176, in GH3 cells.", "content": "We examined the effects of the benzolpyrrole-type Ca2+ channel activator FPL 64176 on voltage-dependent L-type Ca2+ channels in rat anterior pituitary (GH3) cells. FPL 64176 increased K(+)-dependent Ca2+ influx into GH3 cells with an EC50 value of 1.2 x 10(-7) M but had no effect on the binding of [3H]PN200-110 to GH3 cell membranes at concentrations up to 10(-6) M. Whole-cell patch-clamp electrophysiology revealed that FPL 64176 (1 microM) increased L-type Ca2+ channel current amplitude and shifted the current-voltage relationship in the hyperpolarizing direction. Furthermore, Ca2+ channel current activation and deactivation were prolonged. Single-channel analysis showed that FPL 64176 increased both the probability of channel opening and the mean channel open time. Interestingly, the effect of FPL 64176 on channel open time was highly voltage dependent, with much longer openings being observed at more hyperpolarized potentials. We conclude that FPL 64176 represents a new class of L-type Ca2+ channel activator with a novel site and mechanism of action.", "contents": "Characterization of the effects of a new Ca2+ channel activator, FPL 64176, in GH3 cells. We examined the effects of the benzolpyrrole-type Ca2+ channel activator FPL 64176 on voltage-dependent L-type Ca2+ channels in rat anterior pituitary (GH3) cells. FPL 64176 increased K(+)-dependent Ca2+ influx into GH3 cells with an EC50 value of 1.2 x 10(-7) M but had no effect on the binding of [3H]PN200-110 to GH3 cell membranes at concentrations up to 10(-6) M. Whole-cell patch-clamp electrophysiology revealed that FPL 64176 (1 microM) increased L-type Ca2+ channel current amplitude and shifted the current-voltage relationship in the hyperpolarizing direction. Furthermore, Ca2+ channel current activation and deactivation were prolonged. Single-channel analysis showed that FPL 64176 increased both the probability of channel opening and the mean channel open time. Interestingly, the effect of FPL 64176 on channel open time was highly voltage dependent, with much longer openings being observed at more hyperpolarized potentials. We conclude that FPL 64176 represents a new class of L-type Ca2+ channel activator with a novel site and mechanism of action."} {"id": "PMID:1279376", "title": "Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation.", "content": "Extensive behavioral and biochemical characterization of cannabinoid-mediated effects on the central nervous system has revealed at least three lines of evidence supporting the role of a putative guanine nucleotide-binding protein-coupled cannabinoid receptor for cannabimimetic effects, (i) stereoselectivity, (ii) inhibition of the adenylate cyclase/cAMP second messenger system, and (iii) radioligand-binding studies with the synthetic cannabinoid [3H]CP-55,940 indicating a high degree of specific binding to brain tissue preparations. Based on recent findings from our laboratory demonstrating that delta 9-tetrahydrocannabinol markedly inhibited forskolin-stimulated cAMP accumulation in mouse spleen cells, the presence of a guanine nucleotide-binding protein-coupled cannabinoid receptor associated with mouse spleen cells and its functional role in immune modulation were investigated. In the present studies, stereoselective immune modulation was observed with the synthetic bicyclic cannabinoid (-)-CP-55,940 versus (+) CP-56,667 and with 11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl, (-)-HU-210 versus (+)-HU-211. In both cases, the (-)-enantiomer demonstrated greater immunoinhibitory potency than the (+)-isomer, as measured by the in vitro sheep red blood cell antibody-forming cell response. Radioligand binding studies produced a saturation isotherm exhibiting approximately 45-65% specific binding to mouse spleen cells. Scatchard analysis demonstrated a single binding site on spleen cells, possessing a Kd of 910 pM and a Bmax of approximately 1000 receptors/spleen cell. RNA polymerase chain reaction of isolated splenic RNA using specific primers for the cannabinoid receptor resulted in the amplification of a 854-kilobase predicted product that hybridized with cannabinoid receptor cDNA, demonstrating the presence of cannabinoid receptor mRNA in mouse spleen. Together, these findings strongly support the role of a cannabinoid receptor in immune modulation by cannabimimetic agents.", "contents": "Identification of a functionally relevant cannabinoid receptor on mouse spleen cells that is involved in cannabinoid-mediated immune modulation. Extensive behavioral and biochemical characterization of cannabinoid-mediated effects on the central nervous system has revealed at least three lines of evidence supporting the role of a putative guanine nucleotide-binding protein-coupled cannabinoid receptor for cannabimimetic effects, (i) stereoselectivity, (ii) inhibition of the adenylate cyclase/cAMP second messenger system, and (iii) radioligand-binding studies with the synthetic cannabinoid [3H]CP-55,940 indicating a high degree of specific binding to brain tissue preparations. Based on recent findings from our laboratory demonstrating that delta 9-tetrahydrocannabinol markedly inhibited forskolin-stimulated cAMP accumulation in mouse spleen cells, the presence of a guanine nucleotide-binding protein-coupled cannabinoid receptor associated with mouse spleen cells and its functional role in immune modulation were investigated. In the present studies, stereoselective immune modulation was observed with the synthetic bicyclic cannabinoid (-)-CP-55,940 versus (+) CP-56,667 and with 11-OH-delta 8-tetrahydrocannabinol-dimethylheptyl, (-)-HU-210 versus (+)-HU-211. In both cases, the (-)-enantiomer demonstrated greater immunoinhibitory potency than the (+)-isomer, as measured by the in vitro sheep red blood cell antibody-forming cell response. Radioligand binding studies produced a saturation isotherm exhibiting approximately 45-65% specific binding to mouse spleen cells. Scatchard analysis demonstrated a single binding site on spleen cells, possessing a Kd of 910 pM and a Bmax of approximately 1000 receptors/spleen cell. RNA polymerase chain reaction of isolated splenic RNA using specific primers for the cannabinoid receptor resulted in the amplification of a 854-kilobase predicted product that hybridized with cannabinoid receptor cDNA, demonstrating the presence of cannabinoid receptor mRNA in mouse spleen. Together, these findings strongly support the role of a cannabinoid receptor in immune modulation by cannabimimetic agents."} {"id": "PMID:1279377", "title": "Complex pharmacological properties of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtypes.", "content": "The pharmacological properties of two glutamate receptor subtypes, GluR-A/B and GluR-B/D, were examined in RNA-injected Xenopus oocytes using two-electrode voltage clamp. Concentration-response relations revealed that the potencies of L-glutamate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) varied slightly between the two receptor subtypes, but the rank order of agonist potency did not. The EC50 values for GluR-A/B receptors were 3.31 microM for AMPA, 6.16 microM for glutamate, and 57.5 microM for kainate, whereas the EC50 values for GluR-B/D receptors were 5.01 microM, 32.3 microM, and 64.6 microM for AMPA, L-glutamate, and kainate, respectively. The potencies of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) were quantified by Schild analysis. The potency of NBQX at blocking currents mediated by GluR-A/B receptors changed depending on the agonist used to activate the receptors (pA2 values were as follows: for block of kainate, 7.23 +/- 0.01; L-glutamate, 6.78 +/- 0.02; AMPA, 6.95 +/- 0.02). Differences between agonists were less marked in cells expressing GluR-B/D receptors (pA2 values: kainate, 7.28 +/- 0.01; L-glutamate, 7.30 +/- 0.02; AMPA, 7.35 +/- 0.01). In each case, the slope of the Schild regression was not different from unity, consistent with competitive antagonism of these receptors by NBQX. CNQX also blocked GluR-A/B and GluR-B/D receptors competitively but was less potent than NBQX and did not differentiate between agonists or subunit combination. These data suggest that L-glutamate, kainate, and AMPA bind to different receptor substructures on recombinant AMPA receptors and that NBQX but not CNQX binds to these sites with different affinities. Moreover, because the properties of these binding sites vary between GluR-A/B and GluR-B/D receptors, our findings provide a basis for mutational analysis aimed at identifying receptor domains involved in agonist and antagonist binding.", "contents": "Complex pharmacological properties of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subtypes. The pharmacological properties of two glutamate receptor subtypes, GluR-A/B and GluR-B/D, were examined in RNA-injected Xenopus oocytes using two-electrode voltage clamp. Concentration-response relations revealed that the potencies of L-glutamate, kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) varied slightly between the two receptor subtypes, but the rank order of agonist potency did not. The EC50 values for GluR-A/B receptors were 3.31 microM for AMPA, 6.16 microM for glutamate, and 57.5 microM for kainate, whereas the EC50 values for GluR-B/D receptors were 5.01 microM, 32.3 microM, and 64.6 microM for AMPA, L-glutamate, and kainate, respectively. The potencies of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX) were quantified by Schild analysis. The potency of NBQX at blocking currents mediated by GluR-A/B receptors changed depending on the agonist used to activate the receptors (pA2 values were as follows: for block of kainate, 7.23 +/- 0.01; L-glutamate, 6.78 +/- 0.02; AMPA, 6.95 +/- 0.02). Differences between agonists were less marked in cells expressing GluR-B/D receptors (pA2 values: kainate, 7.28 +/- 0.01; L-glutamate, 7.30 +/- 0.02; AMPA, 7.35 +/- 0.01). In each case, the slope of the Schild regression was not different from unity, consistent with competitive antagonism of these receptors by NBQX. CNQX also blocked GluR-A/B and GluR-B/D receptors competitively but was less potent than NBQX and did not differentiate between agonists or subunit combination. These data suggest that L-glutamate, kainate, and AMPA bind to different receptor substructures on recombinant AMPA receptors and that NBQX but not CNQX binds to these sites with different affinities. Moreover, because the properties of these binding sites vary between GluR-A/B and GluR-B/D receptors, our findings provide a basis for mutational analysis aimed at identifying receptor domains involved in agonist and antagonist binding."} {"id": "PMID:1279378", "title": "Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations.", "content": "The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ >> La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ >> Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels.", "contents": "Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations. The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ >> La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ >> Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels."} {"id": "PMID:1279379", "title": "Can nicotine self-inhibition account for its low efficacy at the nicotinic acetylcholine receptor from Torpedo?", "content": "Nicotine, a partial agonist, has a very low efficacy at the nicotinic acetylcholine receptor from Torpedo, but it is not clear whether this is because it is intrinsically poor at opening the ion channel or because, at concentrations that open the channel, it is also capable of blocking it. In this study, we exploited the action of ethanol, which increases the apparent affinity of cholinergic agonists for channel activation, and demonstrated that the weak action of nicotine is consistent with simultaneous activation and inhibition of the receptor. The presence of ethanol increased the efficacy of nicotine, producing an increase in the initial rate of cation efflux from acetylcholine receptor-rich membrane vesicles, as measured by a rapid quench-flow tracer ion assay. The initial rate of efflux increased with ethanol concentration until, in the presence of 1.5 M ethanol, the response to nicotine was indistinguishable from that of the full agonist carbamylcholine. The concentration-response curves for nicotine were bell-shaped, showing activation at low concentrations and inhibition at higher concentrations. Increasing concentrations of ethanol increased the apparent affinity of nicotine for channel activation and decreased its apparent affinity for channel inhibition. These actions broadened the bell-shaped curve, increasing the maximum response until it was equivalent to that of a full agonist. The apparent affinity of nicotine for its inhibitory site, derived from the aforementioned data, agreed with that determined independently by measuring the inhibition by nicotine of initial rates of ion efflux in response to acetylcholine. A value for the apparent affinity of nicotine for channel opening was estimated from the dependence of this parameter on ethanol concentration. When combined, these two parameters predicted the bell-shaped concentration-response curve for the action of nicotine. The results presented in this study are consistent with the notion that the efficacy of nicotine is determined by its relative affinities for channel activation and channel inhibition, but they do not rule out other contributions.", "contents": "Can nicotine self-inhibition account for its low efficacy at the nicotinic acetylcholine receptor from Torpedo? Nicotine, a partial agonist, has a very low efficacy at the nicotinic acetylcholine receptor from Torpedo, but it is not clear whether this is because it is intrinsically poor at opening the ion channel or because, at concentrations that open the channel, it is also capable of blocking it. In this study, we exploited the action of ethanol, which increases the apparent affinity of cholinergic agonists for channel activation, and demonstrated that the weak action of nicotine is consistent with simultaneous activation and inhibition of the receptor. The presence of ethanol increased the efficacy of nicotine, producing an increase in the initial rate of cation efflux from acetylcholine receptor-rich membrane vesicles, as measured by a rapid quench-flow tracer ion assay. The initial rate of efflux increased with ethanol concentration until, in the presence of 1.5 M ethanol, the response to nicotine was indistinguishable from that of the full agonist carbamylcholine. The concentration-response curves for nicotine were bell-shaped, showing activation at low concentrations and inhibition at higher concentrations. Increasing concentrations of ethanol increased the apparent affinity of nicotine for channel activation and decreased its apparent affinity for channel inhibition. These actions broadened the bell-shaped curve, increasing the maximum response until it was equivalent to that of a full agonist. The apparent affinity of nicotine for its inhibitory site, derived from the aforementioned data, agreed with that determined independently by measuring the inhibition by nicotine of initial rates of ion efflux in response to acetylcholine. A value for the apparent affinity of nicotine for channel opening was estimated from the dependence of this parameter on ethanol concentration. When combined, these two parameters predicted the bell-shaped concentration-response curve for the action of nicotine. The results presented in this study are consistent with the notion that the efficacy of nicotine is determined by its relative affinities for channel activation and channel inhibition, but they do not rule out other contributions."} {"id": "PMID:1279382", "title": "Characterization of the calcium response to thyrotropin-releasing hormone (TRH) in cells transfected with TRH receptor complementary DNA: importance of voltage-sensitive calcium channels.", "content": "TRH stimulates a biphasic increase in intracellular free calcium ion, [Ca2+]i. Cells stably transfected with TRH receptor cDNA were used to compare the response in lines with and without L type voltage-gated calcium channels. Rat pituitary GH-Y cells that do not normally express TRH receptors, rat glial C6 cells, and human epithelial Hela cells were transfected with mouse TRH receptor cDNA. All lines bound similar amounts of [3H][N3-Me-His2]TRH with identical affinities (dissociation constant = 1.5 nM). Both pituitary lines expressed L type voltage-gated calcium channels; depolarization with high K+ increased 45Ca2+ uptake 20- to 25-fold and [Ca2+]i 12- to 14-fold. C6 and Hela cells, in contrast, appeared to have no L channel activity. GH4C1 cells responded to TRH with a calcium spike (6-fold) followed by a sustained second phase. When TRH was added after 100 nM nimodipine, an L channel blocker, the initial calcium burst was unaffected but the second phase was abolished. GH-Y cells transfected with TRH receptor cDNA responded to TRH with a 6-fold [Ca2+]i spike followed by a plateau phase (>8 min) in which [Ca2+]i remained elevated or increased. Nimodipine did not alter the peak TRH response or resting [Ca2+]i but reduced the sustained phase, which was eliminated by chelation of extracellular Ca2+. In the transfected glial C6 and Hela cells without calcium channels, TRH evoked transient, monophasic 7- to 9-fold increases in [Ca2+]i, and [Ca2+]i returned to resting levels within 3 min. Thapsigargin stimulated a gradual, large increase in [Ca2+]i in transfected C6 cells, and subsequent addition of TRH caused no further rise. Removal of extracellular Ca2+ from transfected C6 cells shortened the [Ca2+]i responses to TRH, to endothelin 1, and to thapsigargin. The TRH responses were pertussis toxin-insensitive. In summary, TRH can generate a calcium spike in pituitary, C6, and Hela cells transfected with TRH receptor cDNA, but the plateau phase of the [Ca2+]i response is not observed when the receptor is expressed in a cell line without L channel activity.", "contents": "Characterization of the calcium response to thyrotropin-releasing hormone (TRH) in cells transfected with TRH receptor complementary DNA: importance of voltage-sensitive calcium channels. TRH stimulates a biphasic increase in intracellular free calcium ion, [Ca2+]i. Cells stably transfected with TRH receptor cDNA were used to compare the response in lines with and without L type voltage-gated calcium channels. Rat pituitary GH-Y cells that do not normally express TRH receptors, rat glial C6 cells, and human epithelial Hela cells were transfected with mouse TRH receptor cDNA. All lines bound similar amounts of [3H][N3-Me-His2]TRH with identical affinities (dissociation constant = 1.5 nM). Both pituitary lines expressed L type voltage-gated calcium channels; depolarization with high K+ increased 45Ca2+ uptake 20- to 25-fold and [Ca2+]i 12- to 14-fold. C6 and Hela cells, in contrast, appeared to have no L channel activity. GH4C1 cells responded to TRH with a calcium spike (6-fold) followed by a sustained second phase. When TRH was added after 100 nM nimodipine, an L channel blocker, the initial calcium burst was unaffected but the second phase was abolished. GH-Y cells transfected with TRH receptor cDNA responded to TRH with a 6-fold [Ca2+]i spike followed by a plateau phase (>8 min) in which [Ca2+]i remained elevated or increased. Nimodipine did not alter the peak TRH response or resting [Ca2+]i but reduced the sustained phase, which was eliminated by chelation of extracellular Ca2+. In the transfected glial C6 and Hela cells without calcium channels, TRH evoked transient, monophasic 7- to 9-fold increases in [Ca2+]i, and [Ca2+]i returned to resting levels within 3 min. Thapsigargin stimulated a gradual, large increase in [Ca2+]i in transfected C6 cells, and subsequent addition of TRH caused no further rise. Removal of extracellular Ca2+ from transfected C6 cells shortened the [Ca2+]i responses to TRH, to endothelin 1, and to thapsigargin. The TRH responses were pertussis toxin-insensitive. In summary, TRH can generate a calcium spike in pituitary, C6, and Hela cells transfected with TRH receptor cDNA, but the plateau phase of the [Ca2+]i response is not observed when the receptor is expressed in a cell line without L channel activity."} {"id": "PMID:1279380", "title": "[Cloning and structural characteristics of human hair keratin genes rich in sulfur].", "content": "Two human genomic genes for the hair high-sulphur keratins were for the first time cloned in a 15 kb fragment. The primary structures of the coding regions of the genes and their 5'- and 3'-flanks were determined. In the 5'-flanking region, TATA boxes, initiating codons and a 18 nucleotide sequence, previously described in sheep keratin genes and designated as \"the matrix-specific\" sequence was revealed. Basing on the nucleotide sequences, the encoded amino acid sequences of the high-sulphur keratins were determined for the first time. The suggested functional role of the structural elements (regions) revealed in the proteins primary structure and problems concerning their evolution tendencies are discussed.", "contents": "[Cloning and structural characteristics of human hair keratin genes rich in sulfur]. Two human genomic genes for the hair high-sulphur keratins were for the first time cloned in a 15 kb fragment. The primary structures of the coding regions of the genes and their 5'- and 3'-flanks were determined. In the 5'-flanking region, TATA boxes, initiating codons and a 18 nucleotide sequence, previously described in sheep keratin genes and designated as \"the matrix-specific\" sequence was revealed. Basing on the nucleotide sequences, the encoded amino acid sequences of the high-sulphur keratins were determined for the first time. The suggested functional role of the structural elements (regions) revealed in the proteins primary structure and problems concerning their evolution tendencies are discussed."} {"id": "PMID:1279383", "title": "Regulation of expression of the chicken ovalbumin gene: interactions between steroid hormones and second messenger systems.", "content": "The chicken ovalbumin gene is subject to multihormonal regulation. Maximal expression of it requires not only the synergistic effects of estrogen and corticosterone, but also the permissive effects of insulin. In addition to effects on transcription, the stability of its message is greatly enhanced by estrogen. Furthermore, two signal transduction pathways involving protein kinases have been implicated in the regulation of the ovalbumin gene. To better define the role of second messengers on expression of the ovalbumin gene, the effects of the protein kinase-C (PKC) and the cAMP-dependent protein kinase (PKA) pathways on the endogenous levels of ovalbumin mRNA and the transcription of an ovalbumin fusion gene were investigated. Primary cultures of oviduct cells were treated with phorbol 12-myristilate 13-acetate (an activator of PKC) or with forskolin and 3-isobutyl-1-methylxanthine (an activator of PKA) alone, activators plus estrogen and corticosterone, or activators plus both steroids and insulin. The results indicate that phorbol 12-myristilate 13-acetate causes a dramatic destabilization of ovalbumin message, resulting in a reduction in ovalbumin mRNA levels. In contrast, the activators of the PKA system can substitute for insulin and, thereby, increase expression of the ovalbumin gene synergistically with the steroids. The effect of the activators of the PKA system is at the level of transcription. Thus, in chicken oviduct cell cultures, the PKA and PKC signal transduction pathways act in opposing ways to modulate the steroid-induced expression of the ovalbumin gene.", "contents": "Regulation of expression of the chicken ovalbumin gene: interactions between steroid hormones and second messenger systems. The chicken ovalbumin gene is subject to multihormonal regulation. Maximal expression of it requires not only the synergistic effects of estrogen and corticosterone, but also the permissive effects of insulin. In addition to effects on transcription, the stability of its message is greatly enhanced by estrogen. Furthermore, two signal transduction pathways involving protein kinases have been implicated in the regulation of the ovalbumin gene. To better define the role of second messengers on expression of the ovalbumin gene, the effects of the protein kinase-C (PKC) and the cAMP-dependent protein kinase (PKA) pathways on the endogenous levels of ovalbumin mRNA and the transcription of an ovalbumin fusion gene were investigated. Primary cultures of oviduct cells were treated with phorbol 12-myristilate 13-acetate (an activator of PKC) or with forskolin and 3-isobutyl-1-methylxanthine (an activator of PKA) alone, activators plus estrogen and corticosterone, or activators plus both steroids and insulin. The results indicate that phorbol 12-myristilate 13-acetate causes a dramatic destabilization of ovalbumin message, resulting in a reduction in ovalbumin mRNA levels. In contrast, the activators of the PKA system can substitute for insulin and, thereby, increase expression of the ovalbumin gene synergistically with the steroids. The effect of the activators of the PKA system is at the level of transcription. Thus, in chicken oviduct cell cultures, the PKA and PKC signal transduction pathways act in opposing ways to modulate the steroid-induced expression of the ovalbumin gene."} {"id": "PMID:1279381", "title": "[Cloning and expression in Escherichia coli of three Rickettsia prowazekii genes, coding outer membrane proteins].", "content": "Rickettsia prowazekii (virulent Breinl strain) random genomic DNA fragments were cloned in the lambda gt11 expression vector by using non-palindromic adaptors. Several immunoreactive clones were selected after screening 20,000 individual recombinant plaques with human convalescent serum. Some recombinants synthesized the complete 60 K protein, and others synthesized beta-galactosidase fusion polypeptides containing epitopes of 134 K protein of the R. prowazekii outer membrane. The amplified genomic library was screened with monospecific antibodies directed against abundant 31 K and 29.5 K outer membrane proteins. Several recombinant clones expressing full or part of 29.5 K polypeptide, and none expressing 31 K polypeptide were revealed. The serum of a patient convalescing from epidemic typhus did not react in western blot with recombinant 29.5 K protein.", "contents": "[Cloning and expression in Escherichia coli of three Rickettsia prowazekii genes, coding outer membrane proteins]. Rickettsia prowazekii (virulent Breinl strain) random genomic DNA fragments were cloned in the lambda gt11 expression vector by using non-palindromic adaptors. Several immunoreactive clones were selected after screening 20,000 individual recombinant plaques with human convalescent serum. Some recombinants synthesized the complete 60 K protein, and others synthesized beta-galactosidase fusion polypeptides containing epitopes of 134 K protein of the R. prowazekii outer membrane. The amplified genomic library was screened with monospecific antibodies directed against abundant 31 K and 29.5 K outer membrane proteins. Several recombinant clones expressing full or part of 29.5 K polypeptide, and none expressing 31 K polypeptide were revealed. The serum of a patient convalescing from epidemic typhus did not react in western blot with recombinant 29.5 K protein."} {"id": "PMID:1279384", "title": "DNA damage induced mating type switching in Saccharomyces cerevisiae.", "content": "Haploid cells of the yeast Saccharomyces cerevisiae are able to undergo a differentiation-like process: they can switch their mating type between the a and the alpha state. The molecular mechanism of this interconversion of mating types is intrachromosomal gene conversion. It has been shown in a variety of studies that mating type switching in heterothallic strains can be induced by DNA damaging agents, and that different DNA damaging agents differ in the length of incubation after treatment required for induction. Because X-rays induce switching immediately after irradiation and because the DNA double-strand break repair pathway is required for switching, the event initiating heterothallic mating type switching is likely to be a DNA double-strand break. Therefore the assay for heterothallic mating type switching may screen for the induction of DNA double-strand breaks. Several aspects indicating a relationship of mating type switching to mechanisms associated with carcinogenesis are discussed.", "contents": "DNA damage induced mating type switching in Saccharomyces cerevisiae. Haploid cells of the yeast Saccharomyces cerevisiae are able to undergo a differentiation-like process: they can switch their mating type between the a and the alpha state. The molecular mechanism of this interconversion of mating types is intrachromosomal gene conversion. It has been shown in a variety of studies that mating type switching in heterothallic strains can be induced by DNA damaging agents, and that different DNA damaging agents differ in the length of incubation after treatment required for induction. Because X-rays induce switching immediately after irradiation and because the DNA double-strand break repair pathway is required for switching, the event initiating heterothallic mating type switching is likely to be a DNA double-strand break. Therefore the assay for heterothallic mating type switching may screen for the induction of DNA double-strand breaks. Several aspects indicating a relationship of mating type switching to mechanisms associated with carcinogenesis are discussed."} {"id": "PMID:1279385", "title": "Bacterial assays for recombinagens.", "content": "Two principal strategies have been used for studying recombinagenic effects of chemicals and radiation in bacteria: (1) measurement of homologous recombination involving defined alleles in a partially diploid strain, and (2) measurement of the formation and loss of genetic duplications in the bacterial chromosome. In the former category, most methods involve one allele in the bacterial chromosome and another in a plasmid, but it is also possible to detect recombination between two chromosomal alleles or between two extrachromosomal alleles. This review summarizes methods that use each of these approaches for detecting recombination and tabulates data on agents that have been found to be recombinagenic in bacteria. The assays are discussed with respect to their effectiveness in testing for recombinagens and their potential for elucidating mechanisms underlying recombinagenic effects.", "contents": "Bacterial assays for recombinagens. Two principal strategies have been used for studying recombinagenic effects of chemicals and radiation in bacteria: (1) measurement of homologous recombination involving defined alleles in a partially diploid strain, and (2) measurement of the formation and loss of genetic duplications in the bacterial chromosome. In the former category, most methods involve one allele in the bacterial chromosome and another in a plasmid, but it is also possible to detect recombination between two chromosomal alleles or between two extrachromosomal alleles. This review summarizes methods that use each of these approaches for detecting recombination and tabulates data on agents that have been found to be recombinagenic in bacteria. The assays are discussed with respect to their effectiveness in testing for recombinagens and their potential for elucidating mechanisms underlying recombinagenic effects."} {"id": "PMID:1279386", "title": "Tests for recombinagens in fungi.", "content": "Three types of mitotic recombination can be studied in Aspergillus nidulans and Saccharomyces cerevisiae: (1) The classical type of reciprocal mitotic crossing-over which can be detected when it occurs between non-sister chromatids at the four-strand stage followed by co-segregation of a crossing-over and a non-crossing-over chromatid in the subsequent mitotic division. Consequently, mitotic crossing-over reflects cellular responses to primary genetic damage in the G2 phase of the cell cycle. (2) Mitotic gene conversion is a unidirectional event of a localized transfer of genetic information between non-sister chromatids which in yeast can extend to segments of up to 18 cM and even beyond 22 cM in Aspergillus nidulans. Mitotic gene conversion can also occur between unreplicated chromatids and lead to the expression of the newly created genotype without any need for a subsequent mitotic cell division. It reflects a cellular response in G1. (3) Mitotic sister-strand gene conversion can be studied in a recently constructed strain with the same technical ease as classical non-sister chromatid gene conversion. It can be induced by chemicals which do not induce mutation in the Salmonella system and non-sister chromatid gene conversion. Mitotic segregation in Saccharomyces cerevisiae results almost exclusively from crossing-over and gene conversion whereas mitotic chromosomal malsegregation contributes only very little. In contrast to this, in Aspergillus nidulans, both processes contribute considerably so that mitotic segregants always have to be tested for their mechanistic origin.", "contents": "Tests for recombinagens in fungi. Three types of mitotic recombination can be studied in Aspergillus nidulans and Saccharomyces cerevisiae: (1) The classical type of reciprocal mitotic crossing-over which can be detected when it occurs between non-sister chromatids at the four-strand stage followed by co-segregation of a crossing-over and a non-crossing-over chromatid in the subsequent mitotic division. Consequently, mitotic crossing-over reflects cellular responses to primary genetic damage in the G2 phase of the cell cycle. (2) Mitotic gene conversion is a unidirectional event of a localized transfer of genetic information between non-sister chromatids which in yeast can extend to segments of up to 18 cM and even beyond 22 cM in Aspergillus nidulans. Mitotic gene conversion can also occur between unreplicated chromatids and lead to the expression of the newly created genotype without any need for a subsequent mitotic cell division. It reflects a cellular response in G1. (3) Mitotic sister-strand gene conversion can be studied in a recently constructed strain with the same technical ease as classical non-sister chromatid gene conversion. It can be induced by chemicals which do not induce mutation in the Salmonella system and non-sister chromatid gene conversion. Mitotic segregation in Saccharomyces cerevisiae results almost exclusively from crossing-over and gene conversion whereas mitotic chromosomal malsegregation contributes only very little. In contrast to this, in Aspergillus nidulans, both processes contribute considerably so that mitotic segregants always have to be tested for their mechanistic origin."} {"id": "PMID:1279387", "title": "Hereditary conditions in which the loss of heterozygosity may be important.", "content": "Somatic mutations are a common event in multicellular organisms and, therefore, have a significant impact on health. They can lead to either heterozygosity or homozygosity. Since the multistep concept of carcinogenesis presupposes that mutations/deletions of several genes are acquired, the identification and location of the critical genes involved in this sequence is attempted either by the observation of cytogenetic or molecular abnormalities in tumorous tissue or by linkage analysis, or both. The retinoblastoma paradigm of loss of heterozygosity with respect to the loss of the only wild-type allele can be applied to familial neoplasias occurring in all organs as they are summarized in this review. The development of homozygosity in non-malignant tissue has not been extensively investigated. However, its study has contributed to the identification of new genetic phenomena such as parental unidisomy and genomic imprinting.", "contents": "Hereditary conditions in which the loss of heterozygosity may be important. Somatic mutations are a common event in multicellular organisms and, therefore, have a significant impact on health. They can lead to either heterozygosity or homozygosity. Since the multistep concept of carcinogenesis presupposes that mutations/deletions of several genes are acquired, the identification and location of the critical genes involved in this sequence is attempted either by the observation of cytogenetic or molecular abnormalities in tumorous tissue or by linkage analysis, or both. The retinoblastoma paradigm of loss of heterozygosity with respect to the loss of the only wild-type allele can be applied to familial neoplasias occurring in all organs as they are summarized in this review. The development of homozygosity in non-malignant tissue has not been extensively investigated. However, its study has contributed to the identification of new genetic phenomena such as parental unidisomy and genomic imprinting."} {"id": "PMID:1279393", "title": "Mutagen-induced recombination in mammalian cells in vitro.", "content": "It is now clear from in vitro studies that mutagens induce recombination in the cell, both homologous and nonhomologous exchanges. The recombination events induced are extrachromosomal events, exchanges between extrachromosomal DNA and chromosomes, and inter- as well as intrachromosomal exchanges. However, not all types of DNA damage can induce recombination. The mechanisms involved in the induction process are not known but may involve activation of DNA repair systems. In addition, stimulation of mRNA transcription by mutagens, different recombination pathways and how the assay system is constructed may affect the frequency and characteristics of the observed recombination events.", "contents": "Mutagen-induced recombination in mammalian cells in vitro. It is now clear from in vitro studies that mutagens induce recombination in the cell, both homologous and nonhomologous exchanges. The recombination events induced are extrachromosomal events, exchanges between extrachromosomal DNA and chromosomes, and inter- as well as intrachromosomal exchanges. However, not all types of DNA damage can induce recombination. The mechanisms involved in the induction process are not known but may involve activation of DNA repair systems. In addition, stimulation of mRNA transcription by mutagens, different recombination pathways and how the assay system is constructed may affect the frequency and characteristics of the observed recombination events."} {"id": "PMID:1279394", "title": "Insertional mutations in mammals and mammalian cells.", "content": "The retroposon sequences, their mechanisms of transposition and the occurrence of insertional mutation in the mammalian genome are reviewed. Insertional mutations fall into two broad categories: those due to the disruption of a gene following the physical integration of a foreign DNA sequence result in loss of gene product and would be expected to be associated with a recessive mutation. A second class of insertional mutation is well documented in which upon integration the promoter/enhancer activities inherent in the retroposon genome exert their influence on neighboring genes. This promoter/enhancer activity of integrated retroposons may have effects over relatively long distances and thus limit the possibilities of establishing an association between retroposon integration and mutation. It is emphasized that a systematic search for insertional mutations in the mammalian genome involves an extensive two-dimensional array of possible retroposon sequences and mutant alleles. Present results represent only a small portion of the total array. Future studies promise to be fruitful in efforts to isolate genes through insertional tagging, to characterize the mechanisms of retroposon transposition, as well as to study the stability of the mammalian genome.", "contents": "Insertional mutations in mammals and mammalian cells. The retroposon sequences, their mechanisms of transposition and the occurrence of insertional mutation in the mammalian genome are reviewed. Insertional mutations fall into two broad categories: those due to the disruption of a gene following the physical integration of a foreign DNA sequence result in loss of gene product and would be expected to be associated with a recessive mutation. A second class of insertional mutation is well documented in which upon integration the promoter/enhancer activities inherent in the retroposon genome exert their influence on neighboring genes. This promoter/enhancer activity of integrated retroposons may have effects over relatively long distances and thus limit the possibilities of establishing an association between retroposon integration and mutation. It is emphasized that a systematic search for insertional mutations in the mammalian genome involves an extensive two-dimensional array of possible retroposon sequences and mutant alleles. Present results represent only a small portion of the total array. Future studies promise to be fruitful in efforts to isolate genes through insertional tagging, to characterize the mechanisms of retroposon transposition, as well as to study the stability of the mammalian genome."} {"id": "PMID:1279396", "title": "Mechanism and control of recombination in fungi.", "content": "In fungi, most mitotic recombination and at least some meiotic recombination appear to stem from a process of double-strand break repair. During this repair, recombination occurs by conversion caused by the process of double-strand gap filling, by conversion related to heteroduplex formation where homologous molecules interact by complementary base pairing, and by crossing-over which is probably an occasional byproduct of the repair process. From a review of the genetic and biochemical data and the published models of the process of recombination, the following view emerges: broken ends may be acted upon by nucleases and helicases to produce a recombinagenic end which may have both 3' and 5' single-stranded tails. These postulated split-ends may then act independently to find regions of homology with which to react. Invasion by both ends forms two splice-junctions which prime DNA synthesis towards each other to replace lost information, using the homologous sequences as templates. This process would lead to a structure which consists of a double Holliday junction which may be resolved endonucleolytically, sometimes giving a crossover, or by another means such as the action of topoisomerase, to dissolve the structure without a crossover having been formed.", "contents": "Mechanism and control of recombination in fungi. In fungi, most mitotic recombination and at least some meiotic recombination appear to stem from a process of double-strand break repair. During this repair, recombination occurs by conversion caused by the process of double-strand gap filling, by conversion related to heteroduplex formation where homologous molecules interact by complementary base pairing, and by crossing-over which is probably an occasional byproduct of the repair process. From a review of the genetic and biochemical data and the published models of the process of recombination, the following view emerges: broken ends may be acted upon by nucleases and helicases to produce a recombinagenic end which may have both 3' and 5' single-stranded tails. These postulated split-ends may then act independently to find regions of homology with which to react. Invasion by both ends forms two splice-junctions which prime DNA synthesis towards each other to replace lost information, using the homologous sequences as templates. This process would lead to a structure which consists of a double Holliday junction which may be resolved endonucleolytically, sometimes giving a crossover, or by another means such as the action of topoisomerase, to dissolve the structure without a crossover having been formed."} {"id": "PMID:1279398", "title": "Frequency and nature of specific-locus mutations induced in female mice by radiations and chemicals: a review.", "content": "The inducibility of heritable mutations in female mammals has been measured in the mouse specific-locus test (SLT). For radiation-induced mutations, a large body of data has been accumulated that includes information about biological and physical factors that influence mutation yields. However, relatively few SLT studies in females have been conducted with chemicals to date. A single estimate of the spontaneous mutation rate in oocytes, 6/536,207, has been derived as the most appropriate one to subtract from experimental rates. This rate is highly significantly below the spontaneous mutation rate in males. Mutations recovered from females mutagenized at any time after about the 12th day post-conception are induced in non-dividing cells. In adult females, most oocytes are arrested in small follicles; maturation from this stage to ovulation takes several weeks. High-dose-rate radiations are more mutagenic in mature and maturing oocytes than in spermatogonia of the male; on the other hand, no clearly induced mutations have been recovered from irradiated arrested oocytes. Efficient repair processes have been invoked to explain the latter finding as well as the upward-curving dose-effect relation for acute irradiation, and the fact that dose protraction drastically reduces mutation yield from mature and maturing oocytes. The dose-protraction effect is much greater than that found in spermatogonia. Radiation-induced mutation rates in embryonic, fetal, and newborn females are overall lower than those in the mature and maturing oocytes of adults. A dose-protraction effect has also been demonstrated at an early developmental stage when the nuclear morphology of mouse oocytes most resembles that of the human. Of only 5 chemicals so far explored for their effect in oocytes, 2 (ethylnitrosourea, ENU, and triethylenemelamine, TEM), and possibly a third (procarbazine hydrochloride, PRC), are mutagenic--with at least one of these (ENU) mutagenic in arrested as well as maturing oocytes. However, the mutation rate is, in each case, lower than for treated male germ cells. By contrast, ENU-induced mutation yield for the maternal genome of the zygote is an order of magnitude higher than that for the zygote's paternal genome or for spermatogonia. A high proportion of mutants derived from chemical treatment of oocytes (including the oocyte genome in zygotes) are mosaics, probably owing to lesions affecting only 1 strand of the DNA. A characteristic of specific-locus mutations induced in oocytes is that they include a considerably higher percentage of large (multi-locus) lesions (LLs) than do mutations induced in spermatogonia.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Frequency and nature of specific-locus mutations induced in female mice by radiations and chemicals: a review. The inducibility of heritable mutations in female mammals has been measured in the mouse specific-locus test (SLT). For radiation-induced mutations, a large body of data has been accumulated that includes information about biological and physical factors that influence mutation yields. However, relatively few SLT studies in females have been conducted with chemicals to date. A single estimate of the spontaneous mutation rate in oocytes, 6/536,207, has been derived as the most appropriate one to subtract from experimental rates. This rate is highly significantly below the spontaneous mutation rate in males. Mutations recovered from females mutagenized at any time after about the 12th day post-conception are induced in non-dividing cells. In adult females, most oocytes are arrested in small follicles; maturation from this stage to ovulation takes several weeks. High-dose-rate radiations are more mutagenic in mature and maturing oocytes than in spermatogonia of the male; on the other hand, no clearly induced mutations have been recovered from irradiated arrested oocytes. Efficient repair processes have been invoked to explain the latter finding as well as the upward-curving dose-effect relation for acute irradiation, and the fact that dose protraction drastically reduces mutation yield from mature and maturing oocytes. The dose-protraction effect is much greater than that found in spermatogonia. Radiation-induced mutation rates in embryonic, fetal, and newborn females are overall lower than those in the mature and maturing oocytes of adults. A dose-protraction effect has also been demonstrated at an early developmental stage when the nuclear morphology of mouse oocytes most resembles that of the human. Of only 5 chemicals so far explored for their effect in oocytes, 2 (ethylnitrosourea, ENU, and triethylenemelamine, TEM), and possibly a third (procarbazine hydrochloride, PRC), are mutagenic--with at least one of these (ENU) mutagenic in arrested as well as maturing oocytes. However, the mutation rate is, in each case, lower than for treated male germ cells. By contrast, ENU-induced mutation yield for the maternal genome of the zygote is an order of magnitude higher than that for the zygote's paternal genome or for spermatogonia. A high proportion of mutants derived from chemical treatment of oocytes (including the oocyte genome in zygotes) are mosaics, probably owing to lesions affecting only 1 strand of the DNA. A characteristic of specific-locus mutations induced in oocytes is that they include a considerably higher percentage of large (multi-locus) lesions (LLs) than do mutations induced in spermatogonia.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279399", "title": "ENU mutagenesis in the mouse electrophoretic specific-locus test. 2. Mutational studies of mature oocytes.", "content": "Experiments were conducted using the biochemical specific-locus test to assess the mutagenicity of N-ethyl-N-nitrosourea (ENU) in mature oocytes of mice. C57Bl/6J females were treated with 100 mg/kg ENU by intraperitoneal injection and mated to untreated DBA males for 1 week following treatment. 1447 progeny were screened for evidence of mutations affecting the electrophoretic mobility of 32 different proteins; two mutants were detected by electrophoretic analyses. These results provide evidence that ENU is a germ-cell mutagen in mouse mature oocytes, although the frequency of mutants is somewhat lower than that obtained from spermatogonia treated with the same dose.", "contents": "ENU mutagenesis in the mouse electrophoretic specific-locus test. 2. Mutational studies of mature oocytes. Experiments were conducted using the biochemical specific-locus test to assess the mutagenicity of N-ethyl-N-nitrosourea (ENU) in mature oocytes of mice. C57Bl/6J females were treated with 100 mg/kg ENU by intraperitoneal injection and mated to untreated DBA males for 1 week following treatment. 1447 progeny were screened for evidence of mutations affecting the electrophoretic mobility of 32 different proteins; two mutants were detected by electrophoretic analyses. These results provide evidence that ENU is a germ-cell mutagen in mouse mature oocytes, although the frequency of mutants is somewhat lower than that obtained from spermatogonia treated with the same dose."} {"id": "PMID:1279400", "title": "Radiation- and chemically-induced chromosome aberrations in mouse oocytes: a comparison with effects in males.", "content": "Data from studies on radiation- and chemically-induced chromosome aberrations in mouse oocytes have been summarized. An attempt has been made to assess the relative sensitivity to mutagenic agents of female and male germ cells through comparison of observations from mutation studies of female and male mice. No unequivocal evidence of a mutagenic effect limited to a single sex could be found in the cytogenetic data, although differences in relative germ cell sensitivity could be inferred for ionizing radiation and some chemicals. However, the pattern of inter-sex variations was not consistent: for example, irradiation of dictyate oocytes yielded a lower rate of heritable chromosome translocations than the same dose to spermatogonia; in contrast, some chemicals, such as mitomycin C, yielded a larger incidence of chromosome anomalies after treatment of dictyate oocytes than spermatogonia. Overall, the limitations in quality and quantity of cytogenetic data, and the uncertainties associated with comparing information obtained in disparate assays, place severe constraints on the use of observations on induced chromosome aberrations to assess the relative sensitivities of female and male germ cells to environmental mutagens.", "contents": "Radiation- and chemically-induced chromosome aberrations in mouse oocytes: a comparison with effects in males. Data from studies on radiation- and chemically-induced chromosome aberrations in mouse oocytes have been summarized. An attempt has been made to assess the relative sensitivity to mutagenic agents of female and male germ cells through comparison of observations from mutation studies of female and male mice. No unequivocal evidence of a mutagenic effect limited to a single sex could be found in the cytogenetic data, although differences in relative germ cell sensitivity could be inferred for ionizing radiation and some chemicals. However, the pattern of inter-sex variations was not consistent: for example, irradiation of dictyate oocytes yielded a lower rate of heritable chromosome translocations than the same dose to spermatogonia; in contrast, some chemicals, such as mitomycin C, yielded a larger incidence of chromosome anomalies after treatment of dictyate oocytes than spermatogonia. Overall, the limitations in quality and quantity of cytogenetic data, and the uncertainties associated with comparing information obtained in disparate assays, place severe constraints on the use of observations on induced chromosome aberrations to assess the relative sensitivities of female and male germ cells to environmental mutagens."} {"id": "PMID:1279401", "title": "Bleomycin: female-specific dominant lethal effects in mice.", "content": "Limited comparative data in mice indicate that chemical mutagens that induce dominant lethal mutations in males are not necessarily effective in females, but those which are effective in females are generally equally or more effective in males. Recently, however, a few chemicals have been identified that are female-specific with respect to induction of dominant lethal mutations. The antitumor antibiotic adriamycin is among them. Another antitumor antibiotic, bleomycin was examined for its ability to induce dominant lethal mutations in the reproductive cells of male and female mice. No dominant lethal or cytotoxic effects were observed in males treated with bleomycin, even at a maximum tolerated dose. In females, on the other hand, a dose nearly 1/4 of that used in males induced not only a high level of dominant lethal mutations but also killed oocytes in certain stages of follicular development. The effectiveness of bleomycin in inducing dominant lethal mutations in mouse oocytes makes it a valuable tool for investigating whether gonadal transport, inherent differences in the configuration of chromatin in the germ cells of the two sexes or other factors are responsible for the differential susceptibility to bleomycin, which implies potential gender-specific genetic risk in cancer chemotherapy.", "contents": "Bleomycin: female-specific dominant lethal effects in mice. Limited comparative data in mice indicate that chemical mutagens that induce dominant lethal mutations in males are not necessarily effective in females, but those which are effective in females are generally equally or more effective in males. Recently, however, a few chemicals have been identified that are female-specific with respect to induction of dominant lethal mutations. The antitumor antibiotic adriamycin is among them. Another antitumor antibiotic, bleomycin was examined for its ability to induce dominant lethal mutations in the reproductive cells of male and female mice. No dominant lethal or cytotoxic effects were observed in males treated with bleomycin, even at a maximum tolerated dose. In females, on the other hand, a dose nearly 1/4 of that used in males induced not only a high level of dominant lethal mutations but also killed oocytes in certain stages of follicular development. The effectiveness of bleomycin in inducing dominant lethal mutations in mouse oocytes makes it a valuable tool for investigating whether gonadal transport, inherent differences in the configuration of chromatin in the germ cells of the two sexes or other factors are responsible for the differential susceptibility to bleomycin, which implies potential gender-specific genetic risk in cancer chemotherapy."} {"id": "PMID:1279402", "title": "Mutational risks in females: genomic imprinting and maternal molecules.", "content": "Genetic mechanisms for selective mutagenesis in female mammals might include alterations of genomic imprinting, maternally derived molecules, mitochondrial DNA or sex chromosome loci. None of these mechanisms provides an obvious explanation for the higher mutational rates observed for certain mutagens in mouse female pronuclei, but the association of DNA methylation with maternal genomic imprinting is an enticing avenue for research. Further characterization of the extent and homology of genomic imprinting among mammals is required before its relevance to mutagenesis can be determined. The existence of maternal effect mutations in mammals merits evaluation but is not yet proven. The relevance of mitochondrial DNA to female-specific mutagenesis will be greatest in multi-generational studies.", "contents": "Mutational risks in females: genomic imprinting and maternal molecules. Genetic mechanisms for selective mutagenesis in female mammals might include alterations of genomic imprinting, maternally derived molecules, mitochondrial DNA or sex chromosome loci. None of these mechanisms provides an obvious explanation for the higher mutational rates observed for certain mutagens in mouse female pronuclei, but the association of DNA methylation with maternal genomic imprinting is an enticing avenue for research. Further characterization of the extent and homology of genomic imprinting among mammals is required before its relevance to mutagenesis can be determined. The existence of maternal effect mutations in mammals merits evaluation but is not yet proven. The relevance of mitochondrial DNA to female-specific mutagenesis will be greatest in multi-generational studies."} {"id": "PMID:1279403", "title": "Developmental anomalies derived from exposure of zygotes and first-cleavage embryos to mutagens.", "content": "Results of continuing studies indicate that the mouse zygote and two-cell embryo stages are a window of susceptibility in the experimental induction of congenital anomalies with certain mutagenic agents. The mechanisms by which the mutagens initiate the pathogenesis of these developmental defects are not known. However, in certain cases there is evidence that a nonconventional, perhaps epigenetic, mechanism is involved. Detailed characterization of the spectrum of anomalies induced and comparison of responses at the various stages exposed allowed classification of the mutagens generally into two groups. One group is characterized by being effective only in the early stages of zygote development and capable of producing a relatively high incidence of fetal death and hydrops. The other group affects all of the zygote stages studied as well as the two cell-embryo, but does not increase the incidence of fetal death and hydrops. Except for hydrops, chemicals in the two groups do not differ in terms of the types of anomalies present among malformed live fetuses, which bear a resemblance to a subset of common, sporadic human developmental anomalies that are of unknown etiology. This similarity raises the possibility that certain human developmental defects may have their origins in events that happen in the zygote and early pre-implantation stages.", "contents": "Developmental anomalies derived from exposure of zygotes and first-cleavage embryos to mutagens. Results of continuing studies indicate that the mouse zygote and two-cell embryo stages are a window of susceptibility in the experimental induction of congenital anomalies with certain mutagenic agents. The mechanisms by which the mutagens initiate the pathogenesis of these developmental defects are not known. However, in certain cases there is evidence that a nonconventional, perhaps epigenetic, mechanism is involved. Detailed characterization of the spectrum of anomalies induced and comparison of responses at the various stages exposed allowed classification of the mutagens generally into two groups. One group is characterized by being effective only in the early stages of zygote development and capable of producing a relatively high incidence of fetal death and hydrops. The other group affects all of the zygote stages studied as well as the two cell-embryo, but does not increase the incidence of fetal death and hydrops. Except for hydrops, chemicals in the two groups do not differ in terms of the types of anomalies present among malformed live fetuses, which bear a resemblance to a subset of common, sporadic human developmental anomalies that are of unknown etiology. This similarity raises the possibility that certain human developmental defects may have their origins in events that happen in the zygote and early pre-implantation stages."} {"id": "PMID:1279404", "title": "Gene expression in pre-implantation mammalian embryos.", "content": "The pre-implantation mammalian embryo is initially under the control of maternal informational macromolecules that are accumulated during oogenesis. Subsequently, the genetic program of development becomes dependent upon new transcription derived from activation of the embryonic genome. Several embryonic transcripts including those that encode growth factors, cell junction components and plasma membrane ion transporters are required for normal progression of the embryo to the blastocyst stage. The pattern of genes expressed and the overall program of development is subject to the influences of genomic imprinting as well as external influences encountered by the embryo within the maternal reproductive tract.", "contents": "Gene expression in pre-implantation mammalian embryos. The pre-implantation mammalian embryo is initially under the control of maternal informational macromolecules that are accumulated during oogenesis. Subsequently, the genetic program of development becomes dependent upon new transcription derived from activation of the embryonic genome. Several embryonic transcripts including those that encode growth factors, cell junction components and plasma membrane ion transporters are required for normal progression of the embryo to the blastocyst stage. The pattern of genes expressed and the overall program of development is subject to the influences of genomic imprinting as well as external influences encountered by the embryo within the maternal reproductive tract."} {"id": "PMID:1279405", "title": "Gene expression during oogenesis in mice.", "content": "A mouse egg is the end-product of oogenesis--a process initiated during fetal development and completed months later at the time of sperm-egg fusion. Oogenesis includes many important events. Among these are formation of female germ cells, initiation and completion of meiosis, and establishment of a maternal store of materials to support fertilization and preimplantation development. The latter takes place largely during germ cell growth in sexually mature females and involves extensive gene expression. Ribonucleic acid and protein accumulate to unusually high levels during this relatively short phase of oogenesis. Recent studies have demonstrated that establishment of a maternal store of materials in the growing mouse egg is both transcriptionally and translationally regulated. Specific examples of both types of regulation are presented here in the context of gene expression during oogenesis in mice.", "contents": "Gene expression during oogenesis in mice. A mouse egg is the end-product of oogenesis--a process initiated during fetal development and completed months later at the time of sperm-egg fusion. Oogenesis includes many important events. Among these are formation of female germ cells, initiation and completion of meiosis, and establishment of a maternal store of materials to support fertilization and preimplantation development. The latter takes place largely during germ cell growth in sexually mature females and involves extensive gene expression. Ribonucleic acid and protein accumulate to unusually high levels during this relatively short phase of oogenesis. Recent studies have demonstrated that establishment of a maternal store of materials in the growing mouse egg is both transcriptionally and translationally regulated. Specific examples of both types of regulation are presented here in the context of gene expression during oogenesis in mice."} {"id": "PMID:1279406", "title": "Spatial distribution of sperm-derived chromatin in zygotes determined by fluorescence in situ hybridization.", "content": "Fluorescence in situ hybridization was used to determine the spatial distribution of chromatin in zygote pronuclei. A hybrid system involving golden hamster eggs and individual human sperm permitted use of DNA probes specific for the entire human chromosome 4, for the heterochromatic region on the long arm of the human Y chromosome and for unique DNA sequences on human chromosome 19. Chromosome 4 occupied a circumscribed domain in the pronuclei, similar to findings in somatic interphases. Unlike the situation in somatic interphases, the Y heterochromatin was extended throughout the first cell cycle. Pronuclear chromatin was extended 3- to 4-fold compared to somatic interphase chromatin. The extended pronuclear chromatin conformation is likely to affect a zygote's susceptibility to environmental hazards.", "contents": "Spatial distribution of sperm-derived chromatin in zygotes determined by fluorescence in situ hybridization. Fluorescence in situ hybridization was used to determine the spatial distribution of chromatin in zygote pronuclei. A hybrid system involving golden hamster eggs and individual human sperm permitted use of DNA probes specific for the entire human chromosome 4, for the heterochromatic region on the long arm of the human Y chromosome and for unique DNA sequences on human chromosome 19. Chromosome 4 occupied a circumscribed domain in the pronuclei, similar to findings in somatic interphases. Unlike the situation in somatic interphases, the Y heterochromatin was extended throughout the first cell cycle. Pronuclear chromatin was extended 3- to 4-fold compared to somatic interphase chromatin. The extended pronuclear chromatin conformation is likely to affect a zygote's susceptibility to environmental hazards."} {"id": "PMID:1279407", "title": "Chromatin remodeling in mammalian zygotes.", "content": "With sperm-egg fusion at the time of fertilization the gamete nuclei are remodeled from genetically quiescent structures into pronuclei capable of DNA synthesis. Features of this process that are critical to insure the genetic integrity of the zygote and the success of subsequent embryonic development include: oocyte responses that prevent polyspermy; completion of the 2nd meiotic division by the oocyte; exchange of proteins in the sperm nucleus; and, remodelling of the oocyte chromosomes and sperm nucleus into functional pronuclei. Elucidation of the biological and molecular mechanisms underlying zygote formation and chromatin remodeling should enhance our understanding of the potential vulnerability of the zygote to toxicant-induced damage.", "contents": "Chromatin remodeling in mammalian zygotes. With sperm-egg fusion at the time of fertilization the gamete nuclei are remodeled from genetically quiescent structures into pronuclei capable of DNA synthesis. Features of this process that are critical to insure the genetic integrity of the zygote and the success of subsequent embryonic development include: oocyte responses that prevent polyspermy; completion of the 2nd meiotic division by the oocyte; exchange of proteins in the sperm nucleus; and, remodelling of the oocyte chromosomes and sperm nucleus into functional pronuclei. Elucidation of the biological and molecular mechanisms underlying zygote formation and chromatin remodeling should enhance our understanding of the potential vulnerability of the zygote to toxicant-induced damage."} {"id": "PMID:1279408", "title": "Cytoplasmic microtubular dynamics and chromatin organization during mammalian oogenesis and oocyte maturation.", "content": "A chronological series of coordinated alterations in oocyte chromosome and microtubule disposition occur during oogenesis and oocyte maturation in the mammal. Timely transitions in meiotic spindle and cytoplasmic microtubules, due to modifications in both the assembly competence of the tubulin pool and nucleation capacity of centrosomes, underscore key nuclear events during the progressive stages of meiosis I and II. The regulation of these transitional states during meiosis is discussed with respect to hormonal influences imparted to the oocyte within the follicular microenvironment, and the possible ways in which environmental perturbations may result in defective chromosomal partitioning during meiosis.", "contents": "Cytoplasmic microtubular dynamics and chromatin organization during mammalian oogenesis and oocyte maturation. A chronological series of coordinated alterations in oocyte chromosome and microtubule disposition occur during oogenesis and oocyte maturation in the mammal. Timely transitions in meiotic spindle and cytoplasmic microtubules, due to modifications in both the assembly competence of the tubulin pool and nucleation capacity of centrosomes, underscore key nuclear events during the progressive stages of meiosis I and II. The regulation of these transitional states during meiosis is discussed with respect to hormonal influences imparted to the oocyte within the follicular microenvironment, and the possible ways in which environmental perturbations may result in defective chromosomal partitioning during meiosis."} {"id": "PMID:1279409", "title": "Maternal age effect: the enigma of Down syndrome and other trisomic conditions.", "content": "Aneuploidy is the most frequently observed chromosome abnormality in human liveborn, abortuses and oocytes. The only etiological factor that has been established is advanced maternal age for the occurrence of trisomies, particularly trisomy 21 which causes Down syndrome. The maternal age effect remains an enigma. Recent molecular data bearing on this question are reviewed as are the hypotheses that have been proposed linking nondisjunction and maternal age. Rationale is presented for a compromised microcirculation hypothesis that explains the cause of nondisjunction and why its occurrence changes with maternal age from menarche to menopause. It takes into account two facts: (1) 95% of Down syndrome children receive their extra chromosome from their mother, and in 80% or more of these the nondisjunction occurred in the first meiotic division, which is completed in the ovary. (2) The ovarian follicle containing the primary oocyte has no internal circulation. The hypothesis proposes that aneuploid oocytes arise from a concatenation of events. It begins with hormonal imbalance that causes a less-than-optimal microvasculature to develop around the maturing and mature follicles. The resulting decrease in the size of the perifollicular capillary bed reduces the volume of blood flow through the area, leading to an oxygen deficit and a concomitant increase inside the follicle of carbon dioxide and anaerobic products, such as lactic acid. This in turn causes a decrease in the intracellular pH of the oocyte that diminishes the size of the spindle, with consequent displacement and nondisjunction of a chromosome. The compromised microcirculation hypothesis explains the occurrence of aneuploidy in primary and secondary oocytes, sperm precursor cells, tumor and embryonic cells. It also explains why women of all reproductive ages may have a Down syndrome child.", "contents": "Maternal age effect: the enigma of Down syndrome and other trisomic conditions. Aneuploidy is the most frequently observed chromosome abnormality in human liveborn, abortuses and oocytes. The only etiological factor that has been established is advanced maternal age for the occurrence of trisomies, particularly trisomy 21 which causes Down syndrome. The maternal age effect remains an enigma. Recent molecular data bearing on this question are reviewed as are the hypotheses that have been proposed linking nondisjunction and maternal age. Rationale is presented for a compromised microcirculation hypothesis that explains the cause of nondisjunction and why its occurrence changes with maternal age from menarche to menopause. It takes into account two facts: (1) 95% of Down syndrome children receive their extra chromosome from their mother, and in 80% or more of these the nondisjunction occurred in the first meiotic division, which is completed in the ovary. (2) The ovarian follicle containing the primary oocyte has no internal circulation. The hypothesis proposes that aneuploid oocytes arise from a concatenation of events. It begins with hormonal imbalance that causes a less-than-optimal microvasculature to develop around the maturing and mature follicles. The resulting decrease in the size of the perifollicular capillary bed reduces the volume of blood flow through the area, leading to an oxygen deficit and a concomitant increase inside the follicle of carbon dioxide and anaerobic products, such as lactic acid. This in turn causes a decrease in the intracellular pH of the oocyte that diminishes the size of the spindle, with consequent displacement and nondisjunction of a chromosome. The compromised microcirculation hypothesis explains the occurrence of aneuploidy in primary and secondary oocytes, sperm precursor cells, tumor and embryonic cells. It also explains why women of all reproductive ages may have a Down syndrome child."} {"id": "PMID:1279411", "title": "Induction of chromosomal aberrations in Chinese hamster ovary cells by triethyllead acetate.", "content": "Organolead compounds enter the environment primarily through the combustion of leaded gasoline and industrial discharge. Lead and lead-containing compounds have been shown to induce a broad spectrum of toxic effects, including hematopoietic, renal, neurologic, and carcinogenic effects. In this study, the mutagenic activity of triethyllead acetate (Et3PbAc) was determined by measuring the induction of chromosomal aberrations in Chinese hamster ovary cells. The results indicate that Et3PbAc is very cytotoxic and a potent clastogen. In preliminary cytotoxicity studies used to determine appropriate test concentrations for chromosomal aberration analysis, the LC50 of Et3PbAc was approximately 10 microM in the absence of metabolic activation, and 80 microM in the presence of metabolic activation. The maximal response was greater with metabolic activation than without. However, a much higher dose was required to elicit a significant response in the presence of metabolic activation than in its absence.", "contents": "Induction of chromosomal aberrations in Chinese hamster ovary cells by triethyllead acetate. Organolead compounds enter the environment primarily through the combustion of leaded gasoline and industrial discharge. Lead and lead-containing compounds have been shown to induce a broad spectrum of toxic effects, including hematopoietic, renal, neurologic, and carcinogenic effects. In this study, the mutagenic activity of triethyllead acetate (Et3PbAc) was determined by measuring the induction of chromosomal aberrations in Chinese hamster ovary cells. The results indicate that Et3PbAc is very cytotoxic and a potent clastogen. In preliminary cytotoxicity studies used to determine appropriate test concentrations for chromosomal aberration analysis, the LC50 of Et3PbAc was approximately 10 microM in the absence of metabolic activation, and 80 microM in the presence of metabolic activation. The maximal response was greater with metabolic activation than without. However, a much higher dose was required to elicit a significant response in the presence of metabolic activation than in its absence."} {"id": "PMID:1279412", "title": "Assessment of the genotoxic potential of riboflavin and lumiflavin. B. Effect of light.", "content": "On exposure to visible light, riboflavin and lumiflavin produced reactive oxygen species such as singlet oxygen and superoxide radicals. The reaction was found to be time- and concentration-dependent. Both riboflavin and lumiflavin, upon illumination, showed mutagenic response in the umu test as well as in the Ames/Salmonella assay with Salmonella typhimurium TA102. The mutagenic response was partially abolished by superoxide dismutase while sodium azide did not have any effect. No mutagenicity was observed if the compounds were not illuminated. The results suggested the involvement of superoxide radicals in light-induced mutagenicity of riboflavin as well as lumiflavin.", "contents": "Assessment of the genotoxic potential of riboflavin and lumiflavin. B. Effect of light. On exposure to visible light, riboflavin and lumiflavin produced reactive oxygen species such as singlet oxygen and superoxide radicals. The reaction was found to be time- and concentration-dependent. Both riboflavin and lumiflavin, upon illumination, showed mutagenic response in the umu test as well as in the Ames/Salmonella assay with Salmonella typhimurium TA102. The mutagenic response was partially abolished by superoxide dismutase while sodium azide did not have any effect. No mutagenicity was observed if the compounds were not illuminated. The results suggested the involvement of superoxide radicals in light-induced mutagenicity of riboflavin as well as lumiflavin."} {"id": "PMID:1279413", "title": "Induction of micronuclei in tadpoles of Rana temporaria and Xenopus laevis by the pyrethroid Fastac 10 EC.", "content": "The mutagenic properties of the pyrethroid Fastac 10 EC were estimated using the micronucleus test in tadpoles of Rana temporaria and Xenopus laevis. The frequency of erythrocytes with micronuclei was examined in blood smears obtained from animals kept for 14 days in water containing 3 different concentrations of Fastac 10 EC. The study was accompanied by a positive control using the known mutagens cyclophosphamide and N-methyl-N-nitrosourea. The results obtained showed that at high concentrations Fastac 10 EC has a clastogenic activity and/or damages the mitotic spindle, as manifested by a significant increase in the frequency of the micronucleated red blood cells. It was also demonstrated that tadpoles of Rana temporaria are more sensitive to the mutagenic effect of the pyrethroid than are those of Xenopus laevis.", "contents": "Induction of micronuclei in tadpoles of Rana temporaria and Xenopus laevis by the pyrethroid Fastac 10 EC. The mutagenic properties of the pyrethroid Fastac 10 EC were estimated using the micronucleus test in tadpoles of Rana temporaria and Xenopus laevis. The frequency of erythrocytes with micronuclei was examined in blood smears obtained from animals kept for 14 days in water containing 3 different concentrations of Fastac 10 EC. The study was accompanied by a positive control using the known mutagens cyclophosphamide and N-methyl-N-nitrosourea. The results obtained showed that at high concentrations Fastac 10 EC has a clastogenic activity and/or damages the mitotic spindle, as manifested by a significant increase in the frequency of the micronucleated red blood cells. It was also demonstrated that tadpoles of Rana temporaria are more sensitive to the mutagenic effect of the pyrethroid than are those of Xenopus laevis."} {"id": "PMID:1279414", "title": "Influence of lighting conditions on toxicity and genotoxicity of various PAH in the newt in vivo.", "content": "We evaluated the influence of near-ultraviolet light (UVA) on the cytotoxicity and genotoxicity of 7 polycyclic aromatic hydrocarbons (PAH) in larvae of the amphibian Pleurodeles waltl. Benz[a]anthracene (BA), 7,12-benz[a]anthraquinone (BAQ) and anthracene (Ac) proved to be lethal at low doses (some ppb), and the following order of genotoxicity was observed: BA approximately BAQ > DMBA > DMA (9,10-dimethylanthracene). Ac, AQ (9,10-anthraquinone) and DBA (dibenz[a,h]anthracene) were not found to be clastogenic. In the larvae reared in normal conditions (subdued natural daylight/darkness alternation) or in continuous darkness, the BA derivatives were shown to be more genotoxic than BA itself: DMBA > BAQ > BA; BA (> or = 187.5 ppb) slightly increased the level of micronuclei in circulating erythrocytes, while DMBA was strongly clastogenic, in line with their reported carcinogenicity. In other experiments, rearing media alone (i.e., water containing BA, BAQ or DMBA) were UVA-irradiated for 24 h, and then tested on larvae in the dark ('IR-UV/dark' conditions). Photodegradation of BA (50 and 100 ppb) gave rise to clastogenic products. By contrast, DMBA (12.5, 25 or 50 ppb) was destroyed by UVA, and we suggested that any potentially mutagenic photoproducts formed were not in sufficient amounts to yield a positive response in the newt micronucleus test.", "contents": "Influence of lighting conditions on toxicity and genotoxicity of various PAH in the newt in vivo. We evaluated the influence of near-ultraviolet light (UVA) on the cytotoxicity and genotoxicity of 7 polycyclic aromatic hydrocarbons (PAH) in larvae of the amphibian Pleurodeles waltl. Benz[a]anthracene (BA), 7,12-benz[a]anthraquinone (BAQ) and anthracene (Ac) proved to be lethal at low doses (some ppb), and the following order of genotoxicity was observed: BA approximately BAQ > DMBA > DMA (9,10-dimethylanthracene). Ac, AQ (9,10-anthraquinone) and DBA (dibenz[a,h]anthracene) were not found to be clastogenic. In the larvae reared in normal conditions (subdued natural daylight/darkness alternation) or in continuous darkness, the BA derivatives were shown to be more genotoxic than BA itself: DMBA > BAQ > BA; BA (> or = 187.5 ppb) slightly increased the level of micronuclei in circulating erythrocytes, while DMBA was strongly clastogenic, in line with their reported carcinogenicity. In other experiments, rearing media alone (i.e., water containing BA, BAQ or DMBA) were UVA-irradiated for 24 h, and then tested on larvae in the dark ('IR-UV/dark' conditions). Photodegradation of BA (50 and 100 ppb) gave rise to clastogenic products. By contrast, DMBA (12.5, 25 or 50 ppb) was destroyed by UVA, and we suggested that any potentially mutagenic photoproducts formed were not in sufficient amounts to yield a positive response in the newt micronucleus test."} {"id": "PMID:1279415", "title": "Genetic toxicology evaluation of commercial beers, III. SCE, chromosome aberrations, and forward mutation (HGPRT) of commercial beer products in CHO cells.", "content": "Concentrated organic residues extracted from 5 blended aliquots of commercial beers were evaluated for their ability to induce sister chromatid exchange (SCE), chromosomal aberrations and forward mutation in Chinese hamster ovary (CHO) cells. Each extract was prepared by blending 4 commercial beers of similar ingredients and brewing method, passing the beer pool over XAD-2 resin, extracting the resin and concentrating the extract. Studies were performed both with and without metabolic activation using variable amounts of reconstituted residues from 225-fold concentrates of the blended samples. CHO cultures were treated with 0.75 microliters/ml through 10.0 microliters/ml of the concentrates in the SCE assays, 1.0 microliters/ml through 10.0 microliters/ml of the extracts in the aberration assays and 2.5 microliters/ml up to 20 microliters/ml for forward mutation assays. In preliminary screening for SCE as an indicator of potential DNA damage, a significant increase was observed for 3 of 5 concentrated samples; however, no increase in SCE was induced by any of the 5 samples when S9 was added as a source of exogenous metabolic activation. More definitive tests for induction of genetic events, i.e., chromosome aberrations and forward HGPRT mutations, were negative for all 5 extracts whether or not S9 mix was present. Since SCE were not induced in tests with metabolic activation and since there was no concordant aberration or point mutation induction, the preliminary indication of potential DNA damage shown by elevated SCE under conditions without metabolic activation appears to have little biological significance.", "contents": "Genetic toxicology evaluation of commercial beers, III. SCE, chromosome aberrations, and forward mutation (HGPRT) of commercial beer products in CHO cells. Concentrated organic residues extracted from 5 blended aliquots of commercial beers were evaluated for their ability to induce sister chromatid exchange (SCE), chromosomal aberrations and forward mutation in Chinese hamster ovary (CHO) cells. Each extract was prepared by blending 4 commercial beers of similar ingredients and brewing method, passing the beer pool over XAD-2 resin, extracting the resin and concentrating the extract. Studies were performed both with and without metabolic activation using variable amounts of reconstituted residues from 225-fold concentrates of the blended samples. CHO cultures were treated with 0.75 microliters/ml through 10.0 microliters/ml of the concentrates in the SCE assays, 1.0 microliters/ml through 10.0 microliters/ml of the extracts in the aberration assays and 2.5 microliters/ml up to 20 microliters/ml for forward mutation assays. In preliminary screening for SCE as an indicator of potential DNA damage, a significant increase was observed for 3 of 5 concentrated samples; however, no increase in SCE was induced by any of the 5 samples when S9 was added as a source of exogenous metabolic activation. More definitive tests for induction of genetic events, i.e., chromosome aberrations and forward HGPRT mutations, were negative for all 5 extracts whether or not S9 mix was present. Since SCE were not induced in tests with metabolic activation and since there was no concordant aberration or point mutation induction, the preliminary indication of potential DNA damage shown by elevated SCE under conditions without metabolic activation appears to have little biological significance."} {"id": "PMID:1279416", "title": "Mutagenic activity of oxathiolane steroids: structural requirement for the genotoxic activity in Salmonella and E. coli.", "content": "Oxathiolanes and disulfonyl derivatives of steroids were tested for mutagenic activity in the Ames tester strains. The test compounds exhibited mutagenic activity without metabolic activation although metabolic activation markedly enhanced their activity. A significant decrease in the survival of the radiation-sensitive mutants recA, lexA and rer of E. coli was observed as compared to their wild-type counterpart in the presence of the test steroid. Structural features which appear to be crucial for the mutagenic activity in these steroidal drugs are: (i) an electron-donating group at position 3, and (ii) a bulky group anchored at the 5th and 6th positions. The test steroids appear to damage DNA which in turn initiates the SOS repair with the concomitant induction of mutation.", "contents": "Mutagenic activity of oxathiolane steroids: structural requirement for the genotoxic activity in Salmonella and E. coli. Oxathiolanes and disulfonyl derivatives of steroids were tested for mutagenic activity in the Ames tester strains. The test compounds exhibited mutagenic activity without metabolic activation although metabolic activation markedly enhanced their activity. A significant decrease in the survival of the radiation-sensitive mutants recA, lexA and rer of E. coli was observed as compared to their wild-type counterpart in the presence of the test steroid. Structural features which appear to be crucial for the mutagenic activity in these steroidal drugs are: (i) an electron-donating group at position 3, and (ii) a bulky group anchored at the 5th and 6th positions. The test steroids appear to damage DNA which in turn initiates the SOS repair with the concomitant induction of mutation."} {"id": "PMID:1279417", "title": "Assessment of the genotoxic potential of riboflavin and lumiflavin. A. Effect of metabolic enzymes.", "content": "The mutagenic potential of riboflavin and its photodegradation product lumiflavin was evaluated using the umu test, SOS chromotest and Ames Salmonella assay. Both riboflavin and lumiflavin by themselves were found to be non-mutagenic. On treatment with rat liver microsomal enzymes (S9) or caecal cell-free extract (CCE), lumiflavin acquired mutagenicity, while the status of riboflavin remained unaffected. Activation of lumiflavin by metabolic enzymes was found to result in an alteration of its spectral characteristics.", "contents": "Assessment of the genotoxic potential of riboflavin and lumiflavin. A. Effect of metabolic enzymes. The mutagenic potential of riboflavin and its photodegradation product lumiflavin was evaluated using the umu test, SOS chromotest and Ames Salmonella assay. Both riboflavin and lumiflavin by themselves were found to be non-mutagenic. On treatment with rat liver microsomal enzymes (S9) or caecal cell-free extract (CCE), lumiflavin acquired mutagenicity, while the status of riboflavin remained unaffected. Activation of lumiflavin by metabolic enzymes was found to result in an alteration of its spectral characteristics."} {"id": "PMID:1279418", "title": "Polymorphism in the circumsporozoite protein of the human malaria parasite Plasmodium vivax.", "content": "The circumsporozoite (CS) protein that covers the surface of infectious sporozoites is a candidate antigen in malaria vaccine development. To determine the extent of B- and T-epitope polymorphism and to understand the mechanisms of antigenic variability, we have characterized the CS protein gene of Plasmodium vivax from field isolates representing geographically distant regions of Papua New Guinea (PNG) and Brazil. In the central repeat region of the CS protein, in addition to variation in the number of repeats, an array of mutations was observed which suggests that point mutations have led to the emergence of the variant CS repeat sequence ANGA(G/D)(N/D)QPG from GDRA(D/A)GQPA. Outside the repeat region of the protein, the nonsilent nucleotide substitutions of independent origin are localized in three domains of the protein that either harbor known T-cell determinants or are analogous to the Plasmodium falciparum immunodominant determinants, Th2R and Th3R. We have found that, with the exception of one CS clone sequence that was shared by one P. vivax isolate each from PNG and Brazil, the P. vivax CS protein types can be grouped into Papuan and Brazilian types. These results suggest that an in-depth study of parasite population dynamics is required before field trials for vaccine formulation based on polymorphic immunodominant determinants are conducted.", "contents": "Polymorphism in the circumsporozoite protein of the human malaria parasite Plasmodium vivax. The circumsporozoite (CS) protein that covers the surface of infectious sporozoites is a candidate antigen in malaria vaccine development. To determine the extent of B- and T-epitope polymorphism and to understand the mechanisms of antigenic variability, we have characterized the CS protein gene of Plasmodium vivax from field isolates representing geographically distant regions of Papua New Guinea (PNG) and Brazil. In the central repeat region of the CS protein, in addition to variation in the number of repeats, an array of mutations was observed which suggests that point mutations have led to the emergence of the variant CS repeat sequence ANGA(G/D)(N/D)QPG from GDRA(D/A)GQPA. Outside the repeat region of the protein, the nonsilent nucleotide substitutions of independent origin are localized in three domains of the protein that either harbor known T-cell determinants or are analogous to the Plasmodium falciparum immunodominant determinants, Th2R and Th3R. We have found that, with the exception of one CS clone sequence that was shared by one P. vivax isolate each from PNG and Brazil, the P. vivax CS protein types can be grouped into Papuan and Brazilian types. These results suggest that an in-depth study of parasite population dynamics is required before field trials for vaccine formulation based on polymorphic immunodominant determinants are conducted."} {"id": "PMID:1279419", "title": "Inhibitory monoclonal antibodies recognise epitopes adjacent to a proteolytic cleavage site on the RAP-1 protein of Plasmodium falciparum.", "content": "The low-molecular-weight rhoptry-associated protein (RAP) complex of Plasmodium falciparum consists of at least two gene products, RAP-1 and RAP-2, and has the ability to immunise Saimiri monkeys against experimental P. falciparum infection. Several monoclonal antibodies specifically recognise this complex and in this study we show that purified immunoglobulin derived from these monoclonals is capable of inhibiting parasite growth in vitro. It has previously been shown that RAP-1 initially appears as an 80-kDa protein (p80) in early schizogony and is processed to a 65-kDa protein (p65) in late schizogony. Several of the inhibitory monoclonals recognise both the 80- and 65-kDa proteins by Western blot analysis suggesting that they recognise linear epitopes on RAP-1. We have mapped these epitopes by testing the reactivity of the monoclonals against fragments of the rap-1 gene expressed as beta-galactosidase fusion proteins and subsequently against synthetic peptides. All of the epitopes map to a region 10-20 amino acids C-terminal to the proteolytic cleavage site for the processing of p80 to p65 at amino acid 190. We also show that the 65-kDa protein is not present in purified merozoites, suggesting that its generation is associated with merozoite release rather than erythrocyte invasion. These results are discussed with respect to possible inhibitory mechanisms for the monoclonals.", "contents": "Inhibitory monoclonal antibodies recognise epitopes adjacent to a proteolytic cleavage site on the RAP-1 protein of Plasmodium falciparum. The low-molecular-weight rhoptry-associated protein (RAP) complex of Plasmodium falciparum consists of at least two gene products, RAP-1 and RAP-2, and has the ability to immunise Saimiri monkeys against experimental P. falciparum infection. Several monoclonal antibodies specifically recognise this complex and in this study we show that purified immunoglobulin derived from these monoclonals is capable of inhibiting parasite growth in vitro. It has previously been shown that RAP-1 initially appears as an 80-kDa protein (p80) in early schizogony and is processed to a 65-kDa protein (p65) in late schizogony. Several of the inhibitory monoclonals recognise both the 80- and 65-kDa proteins by Western blot analysis suggesting that they recognise linear epitopes on RAP-1. We have mapped these epitopes by testing the reactivity of the monoclonals against fragments of the rap-1 gene expressed as beta-galactosidase fusion proteins and subsequently against synthetic peptides. All of the epitopes map to a region 10-20 amino acids C-terminal to the proteolytic cleavage site for the processing of p80 to p65 at amino acid 190. We also show that the 65-kDa protein is not present in purified merozoites, suggesting that its generation is associated with merozoite release rather than erythrocyte invasion. These results are discussed with respect to possible inhibitory mechanisms for the monoclonals."} {"id": "PMID:1279420", "title": "Surface epitope localization and gene structure of a Babesia bovis 44-kilodalton variable merozoite surface antigen.", "content": "Variation of Babesia bovis merozoite surface antigens occurs among geographic strains of the parasite. In this and a concurrent report, we investigate this variation at the gene and protein level. Using a monoclonal antibody (mAb 23/70.174), B. bovis gene sequences were identified that encoded a surface epitope of a 44-kDa merozoite surface antigen (MSA-2). This epitope is variably expressed among geographic isolates of B. bovis. Here, we describe the MSA-2 protein gene sequence, localize this surface epitope to a repeated amino acid sequence, and investigate the genomic organization of the gene in B. bovis strains from Mexico and Australia. The predicted protein sequence had hydrophobic regions at its amino and carboxy termini consistent with a signal peptide and a membrane anchor via glycosylphosphatidyl inositol, respectively. The surface epitope recognized by mAb 23/70.174 was localized within a 24-amino acid sequence which is repeated twice in tandem. Six different EcoRI bands hybridized to the MSA-2 gene sequence with varying intensities in genomic Southern blots of the homologous strain. Two of these appear to be alleles of the MSA-2 gene. Whereas 5' and 3' sequences of the MSA-2 gene sequence were detected in an Australia strain of B. bovis, internal gene sequences encoding the surface epitope were not. The 3' sequences of the MSA-2 gene also had significant sequence similarity with the MSA-1 gene of the Mexico strain B. bovis and a gene from the previously described BabR locus. These data indicate that the MSA-2 protein gene belongs to the BabR locus which encodes variable merozoite surface antigens.", "contents": "Surface epitope localization and gene structure of a Babesia bovis 44-kilodalton variable merozoite surface antigen. Variation of Babesia bovis merozoite surface antigens occurs among geographic strains of the parasite. In this and a concurrent report, we investigate this variation at the gene and protein level. Using a monoclonal antibody (mAb 23/70.174), B. bovis gene sequences were identified that encoded a surface epitope of a 44-kDa merozoite surface antigen (MSA-2). This epitope is variably expressed among geographic isolates of B. bovis. Here, we describe the MSA-2 protein gene sequence, localize this surface epitope to a repeated amino acid sequence, and investigate the genomic organization of the gene in B. bovis strains from Mexico and Australia. The predicted protein sequence had hydrophobic regions at its amino and carboxy termini consistent with a signal peptide and a membrane anchor via glycosylphosphatidyl inositol, respectively. The surface epitope recognized by mAb 23/70.174 was localized within a 24-amino acid sequence which is repeated twice in tandem. Six different EcoRI bands hybridized to the MSA-2 gene sequence with varying intensities in genomic Southern blots of the homologous strain. Two of these appear to be alleles of the MSA-2 gene. Whereas 5' and 3' sequences of the MSA-2 gene sequence were detected in an Australia strain of B. bovis, internal gene sequences encoding the surface epitope were not. The 3' sequences of the MSA-2 gene also had significant sequence similarity with the MSA-1 gene of the Mexico strain B. bovis and a gene from the previously described BabR locus. These data indicate that the MSA-2 protein gene belongs to the BabR locus which encodes variable merozoite surface antigens."} {"id": "PMID:1279421", "title": "Neutralization-sensitive merozoite surface antigens of Babesia bovis encoded by members of a polymorphic gene family.", "content": "Monospecific antibodies against native and recombinant versions of the major merozoite surface antigen (MSA-1) of Babesia bovis neutralize the infectivity of merozoites from Texas and Mexico strains in vitro. Sequence analysis shows that MSA-1 and a related, co-expressed 44 kDa merozoite surface protein (MSA-2) are encoded by members of a multigene family previously designated BabR. BabR genes, originally described in Australia strains of B. bovis, are notable because their marked polymorphism is apparently mediated by chromosomal rearrangements, but protein products of BabR genes have not previously been identified. The 3' terminal 173 nucleotides of the MSA-1 gene, including 60 nucleotides of untranslated sequence, are highly similar to the 3' terminal sequences of BabR 0.8 (84% identity) and MSA-2 (94% identity). Alignment of the predicted protein sequences demonstrates significant overall homology between MSA-1 and MSA-2, and between both proteins and the amino terminal BabR sequence. MSA-1 nucleic acid probes also hybridize weakly to genomic DNA from the Australia 'L' strain, even though this strain does not express merozoite surface epitopes cross-reactive with MSA-1 or MSA-2. Hybridization of these same probes to genomic DNA from the cloned Mexico strain reveals a pattern of bands compatible with two copies each of MSA-1 and MSA-2. Proteins encoded by this B. bovis gene family have been designated variable merozoite surface antigens (VMSA). The extent and mechanism of VMSA polymorphism among strains will be important when evaluating the role these surface proteins have in the host-parasite interaction, including immunity to blood stages.", "contents": "Neutralization-sensitive merozoite surface antigens of Babesia bovis encoded by members of a polymorphic gene family. Monospecific antibodies against native and recombinant versions of the major merozoite surface antigen (MSA-1) of Babesia bovis neutralize the infectivity of merozoites from Texas and Mexico strains in vitro. Sequence analysis shows that MSA-1 and a related, co-expressed 44 kDa merozoite surface protein (MSA-2) are encoded by members of a multigene family previously designated BabR. BabR genes, originally described in Australia strains of B. bovis, are notable because their marked polymorphism is apparently mediated by chromosomal rearrangements, but protein products of BabR genes have not previously been identified. The 3' terminal 173 nucleotides of the MSA-1 gene, including 60 nucleotides of untranslated sequence, are highly similar to the 3' terminal sequences of BabR 0.8 (84% identity) and MSA-2 (94% identity). Alignment of the predicted protein sequences demonstrates significant overall homology between MSA-1 and MSA-2, and between both proteins and the amino terminal BabR sequence. MSA-1 nucleic acid probes also hybridize weakly to genomic DNA from the Australia 'L' strain, even though this strain does not express merozoite surface epitopes cross-reactive with MSA-1 or MSA-2. Hybridization of these same probes to genomic DNA from the cloned Mexico strain reveals a pattern of bands compatible with two copies each of MSA-1 and MSA-2. Proteins encoded by this B. bovis gene family have been designated variable merozoite surface antigens (VMSA). The extent and mechanism of VMSA polymorphism among strains will be important when evaluating the role these surface proteins have in the host-parasite interaction, including immunity to blood stages."} {"id": "PMID:1279428", "title": "Keratinolysis by Absidia cylindrospora and Rhizomucor pusillus: biochemical proof.", "content": "Absidia cylindrospora and Rhizomucor pusillus causal agents of phycomycoses, were cultured on sterile natural keratins in a mineral solution and the keratin degradation products analyzed. The excess of sulphur was removed by oxidation to inorganic sulphate and thiosulphate, which were the main products of sulphitolysis of keratin. The proteolytic activity of the two fungi depended on the nature of the keratin substrate. Human scalp hair was the most favoured keratin substrate by both the fungi.", "contents": "Keratinolysis by Absidia cylindrospora and Rhizomucor pusillus: biochemical proof. Absidia cylindrospora and Rhizomucor pusillus causal agents of phycomycoses, were cultured on sterile natural keratins in a mineral solution and the keratin degradation products analyzed. The excess of sulphur was removed by oxidation to inorganic sulphate and thiosulphate, which were the main products of sulphitolysis of keratin. The proteolytic activity of the two fungi depended on the nature of the keratin substrate. Human scalp hair was the most favoured keratin substrate by both the fungi."} {"id": "PMID:1279429", "title": "Effects of 5-vinyloxazolidine-2-thione on lactating rats and their sucklings.", "content": "5-vinyloxazolidine-2-thione (VOT) administered orally to lactating rats was found to be efficiently transferred to the sucklings via the milk. In mothers the exposure to VOT resulted in an increased percentage of neutrophils, a decreased percentage of lymphocytes and increases in the relative weights of liver and thyroid. Suckling rats showed a decreased number of leucocytes, increases in the relative weights of liver and thyroid and structural changes in the thyroid. Male sucklings were more affected than female pups. The antithyroid effects were clearly related to the maternally administered VOT doses.", "contents": "Effects of 5-vinyloxazolidine-2-thione on lactating rats and their sucklings. 5-vinyloxazolidine-2-thione (VOT) administered orally to lactating rats was found to be efficiently transferred to the sucklings via the milk. In mothers the exposure to VOT resulted in an increased percentage of neutrophils, a decreased percentage of lymphocytes and increases in the relative weights of liver and thyroid. Suckling rats showed a decreased number of leucocytes, increases in the relative weights of liver and thyroid and structural changes in the thyroid. Male sucklings were more affected than female pups. The antithyroid effects were clearly related to the maternally administered VOT doses."} {"id": "PMID:1279430", "title": "Signal-sequence recognition by an Escherichia coli ribonucleoprotein complex.", "content": "Hydrophobic signal-sequences direct the transfer of secretory proteins across the inner membrane of prokaryotes and the endoplasmic reticulum membranes of eukaryotes. In mammalian cells, signal-sequences are recognized by the 54K protein (M(r) 54,000) of the signal recognition particle (SRP) which is believed to hold the nascent chain in a translocation-competent conformation until it contacts the endoplasmic reticulum membrane. The SRP consists of a 7S RNA and six different polypeptides. The 7S RNA and the 54K signal-sequence-binding protein (SRP54) of mammalian SRP exhibit strong sequence similarity to the 4.5S RNA and P48 protein (Ffh) of Escherichia coli which form a ribonucleoprotein particle. Depletion of 4.5S RNA or overproduction of P48 causes the accumulation of the beta-lactamase precursor, although not of other secretory proteins. Whether 4.5S RNA and P48 are part of an SRP-like complex with a role in protein export is controversial. Here we show that the P48/4.5S RNA ribonucleoprotein complex interacts specifically with the signal sequence of a nascent secretory protein and therefore is a signal recognition particle.", "contents": "Signal-sequence recognition by an Escherichia coli ribonucleoprotein complex. Hydrophobic signal-sequences direct the transfer of secretory proteins across the inner membrane of prokaryotes and the endoplasmic reticulum membranes of eukaryotes. In mammalian cells, signal-sequences are recognized by the 54K protein (M(r) 54,000) of the signal recognition particle (SRP) which is believed to hold the nascent chain in a translocation-competent conformation until it contacts the endoplasmic reticulum membrane. The SRP consists of a 7S RNA and six different polypeptides. The 7S RNA and the 54K signal-sequence-binding protein (SRP54) of mammalian SRP exhibit strong sequence similarity to the 4.5S RNA and P48 protein (Ffh) of Escherichia coli which form a ribonucleoprotein particle. Depletion of 4.5S RNA or overproduction of P48 causes the accumulation of the beta-lactamase precursor, although not of other secretory proteins. Whether 4.5S RNA and P48 are part of an SRP-like complex with a role in protein export is controversial. Here we show that the P48/4.5S RNA ribonucleoprotein complex interacts specifically with the signal sequence of a nascent secretory protein and therefore is a signal recognition particle."} {"id": "PMID:1279431", "title": "Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis.", "content": "Inefficient vascular supply and the resultant reduction in tissue oxygen tension often lead to neovascularization in order to satisfy the needs of the tissue. Examples include the compensatory development of collateral blood vessels in ischaemic tissues that are otherwise quiescent for angiogenesis and angiogenesis associated with the healing of hypoxic wounds. But the presumptive hypoxia-induced angiogenic factors that mediate this feedback response have not been identified. Here we show that vascular endothelial growth factor (VEGF; also known as vascular permeability factor) probably functions as a hypoxia-inducible angiogenic factor. VEGF messenger RNA levels are dramatically increased within a few hours of exposing different cell cultures to hypoxia and return to background when normal oxygen supply is resumed. In situ analysis of tumour specimens undergoing neovascularization show that the production of VEGF is specifically induced in a subset of glioblastoma cells distinguished by their immediate proximity to necrotic foci (presumably hypoxic regions) and the clustering of capillaries alongside VEGF-producing cells.", "contents": "Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Inefficient vascular supply and the resultant reduction in tissue oxygen tension often lead to neovascularization in order to satisfy the needs of the tissue. Examples include the compensatory development of collateral blood vessels in ischaemic tissues that are otherwise quiescent for angiogenesis and angiogenesis associated with the healing of hypoxic wounds. But the presumptive hypoxia-induced angiogenic factors that mediate this feedback response have not been identified. Here we show that vascular endothelial growth factor (VEGF; also known as vascular permeability factor) probably functions as a hypoxia-inducible angiogenic factor. VEGF messenger RNA levels are dramatically increased within a few hours of exposing different cell cultures to hypoxia and return to background when normal oxygen supply is resumed. In situ analysis of tumour specimens undergoing neovascularization show that the production of VEGF is specifically induced in a subset of glioblastoma cells distinguished by their immediate proximity to necrotic foci (presumably hypoxic regions) and the clustering of capillaries alongside VEGF-producing cells."} {"id": "PMID:1279432", "title": "Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo.", "content": "Clinical and experimental studies suggest that angiogenesis is a prerequisite for solid tumour growth. Several growth factors with mitogenic or chemotactic activity for endothelial cells in vitro have been described, but it is not known whether these mediate tumour vascularization in vivo. Glioblastoma, the most common and most malignant brain tumour in humans, is distinguished from astrocytoma by the presence of necroses and vascular proliferations. Here we show that expression of an endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), is induced in astrocytoma cells but is dramatically upregulated in two apparently different subsets of glioblastoma cells. The high-affinity tyrosine kinase receptor for VEGF, flt, although not expressed in normal brain endothelium, is upregulated in tumour endothelial cells in vivo. These observations strongly support the concept that tumour angiogenesis is regulated by paracrine mechanisms and identify VEGF as a potential tumour angiogenesis factor in vivo.", "contents": "Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Clinical and experimental studies suggest that angiogenesis is a prerequisite for solid tumour growth. Several growth factors with mitogenic or chemotactic activity for endothelial cells in vitro have been described, but it is not known whether these mediate tumour vascularization in vivo. Glioblastoma, the most common and most malignant brain tumour in humans, is distinguished from astrocytoma by the presence of necroses and vascular proliferations. Here we show that expression of an endothelial cell-specific mitogen, vascular endothelial growth factor (VEGF), is induced in astrocytoma cells but is dramatically upregulated in two apparently different subsets of glioblastoma cells. The high-affinity tyrosine kinase receptor for VEGF, flt, although not expressed in normal brain endothelium, is upregulated in tumour endothelial cells in vivo. These observations strongly support the concept that tumour angiogenesis is regulated by paracrine mechanisms and identify VEGF as a potential tumour angiogenesis factor in vivo."} {"id": "PMID:1279433", "title": "Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets.", "content": "The glycoprotein P-selectin is a cell adhesion molecule of stimulated platelets and endothelial cells, which mediates the interaction of these cells with neutrophils and monocytes. It is a membrane component of cell storage granules, and is a member of the selectin family which includes E-selectin and L-selectin. P-selectin recognizes both lineage-specific carbohydrate ligands on monocytes and neutrophils, including the Lewis x antigen, sialic acid, and a protein component. In inflammation and thrombosis, P-selectin may mediate the interaction of leukocytes with platelets bound in the region of tissue injury and with stimulated endothelium. To evaluate the role of P-selectin in platelet-leukocyte adhesion in vivo, the accumulation of leukocytes within an experimental thrombus was explored in an arteriovenous shunt model in baboons. A Dacron graft implanted within an arteriovenous shunt is thrombogenic, accumulating platelets and fibrin within its lumen. These bound platelets express P-selectin. Here we show that antibody inhibition of leukocyte binding to P-selectin expressed on platelets immobilized on the graft blocks leukocyte accumulation and inhibits the deposition of fibrin within the thrombus. These results indicate that P-selectin is an important adhesion molecule on platelets, mediating platelet-leukocyte binding in vivo, that the presence of leukocytes in thrombi is mediated by P-selectin, and that these leukocytes promote fibrin deposition.", "contents": "Leukocyte accumulation promoting fibrin deposition is mediated in vivo by P-selectin on adherent platelets. The glycoprotein P-selectin is a cell adhesion molecule of stimulated platelets and endothelial cells, which mediates the interaction of these cells with neutrophils and monocytes. It is a membrane component of cell storage granules, and is a member of the selectin family which includes E-selectin and L-selectin. P-selectin recognizes both lineage-specific carbohydrate ligands on monocytes and neutrophils, including the Lewis x antigen, sialic acid, and a protein component. In inflammation and thrombosis, P-selectin may mediate the interaction of leukocytes with platelets bound in the region of tissue injury and with stimulated endothelium. To evaluate the role of P-selectin in platelet-leukocyte adhesion in vivo, the accumulation of leukocytes within an experimental thrombus was explored in an arteriovenous shunt model in baboons. A Dacron graft implanted within an arteriovenous shunt is thrombogenic, accumulating platelets and fibrin within its lumen. These bound platelets express P-selectin. Here we show that antibody inhibition of leukocyte binding to P-selectin expressed on platelets immobilized on the graft blocks leukocyte accumulation and inhibits the deposition of fibrin within the thrombus. These results indicate that P-selectin is an important adhesion molecule on platelets, mediating platelet-leukocyte binding in vivo, that the presence of leukocytes in thrombi is mediated by P-selectin, and that these leukocytes promote fibrin deposition."} {"id": "PMID:1279434", "title": "Crystal structure of a Src-homology 3 (SH3) domain.", "content": "The Src-homologous SH3 domain is a small domain present in a large number of proteins that are involved in signal transduction, such as the Src protein tyrosine kinase, or in membrane-cytoskeleton interactions, but the function of SH3 is still unknown (reviewed in refs 1-3). Here we report the three-dimensional structure at 1.8 A resolution of the SH3 domain of the cytoskeletal protein spectrin expressed in Escherichia coli. The domain is a compact beta-barrel made of five antiparallel beta-strands. The amino acids that are conserved in the SH3 sequences are located close to each other on one side of the molecule. This surface is rich in aromatic and carboxylic amino acids, and is distal to the region of the molecule where the N and C termini reside and where SH3 inserts into the alpha-spectrin chain. We suggest that a protein ligand binds to this conserved surface of SH3.", "contents": "Crystal structure of a Src-homology 3 (SH3) domain. The Src-homologous SH3 domain is a small domain present in a large number of proteins that are involved in signal transduction, such as the Src protein tyrosine kinase, or in membrane-cytoskeleton interactions, but the function of SH3 is still unknown (reviewed in refs 1-3). Here we report the three-dimensional structure at 1.8 A resolution of the SH3 domain of the cytoskeletal protein spectrin expressed in Escherichia coli. The domain is a compact beta-barrel made of five antiparallel beta-strands. The amino acids that are conserved in the SH3 sequences are located close to each other on one side of the molecule. This surface is rich in aromatic and carboxylic amino acids, and is distal to the region of the molecule where the N and C termini reside and where SH3 inserts into the alpha-spectrin chain. We suggest that a protein ligand binds to this conserved surface of SH3."} {"id": "PMID:1279436", "title": "Control of CFTR chloride conductance by ATP levels through non-hydrolytic binding.", "content": "Site-specific mutation and membrane reconstitution experiments provide compelling evidence that the product of the gene which is at fault in the disease cystic fibrosis, termed the cystic fibrosis transmembrane conductance regulator (CFTR), is a small-conductance chloride channel activated by phosphorylation. As transport of chloride ions is passive, the predicted presence of two nucleotide-binding domains in CFTR seems as puzzling as a report that ATP hydrolysis is essential to activate the channel. We now find that in the sweat duct, which expresses high levels of CFTR and has a very high Cl- conductance, intracellular concentrations of ATP must be about normal (5 mM) for activation of this conductance, apparently by a non-hydrolytic, perhaps allosteric, mechanism. This passive dependence on ATP should mean that even a modest depletion of cell energy levels will significantly lower the energy demands of electrolyte transport by decreasing chloride conductance. We believe this direct coupling between cellular ATP levels and chloride channel activity is an adaptive mechanism to protect the tissue from damage resulting from excessive energy depletion.", "contents": "Control of CFTR chloride conductance by ATP levels through non-hydrolytic binding. Site-specific mutation and membrane reconstitution experiments provide compelling evidence that the product of the gene which is at fault in the disease cystic fibrosis, termed the cystic fibrosis transmembrane conductance regulator (CFTR), is a small-conductance chloride channel activated by phosphorylation. As transport of chloride ions is passive, the predicted presence of two nucleotide-binding domains in CFTR seems as puzzling as a report that ATP hydrolysis is essential to activate the channel. We now find that in the sweat duct, which expresses high levels of CFTR and has a very high Cl- conductance, intracellular concentrations of ATP must be about normal (5 mM) for activation of this conductance, apparently by a non-hydrolytic, perhaps allosteric, mechanism. This passive dependence on ATP should mean that even a modest depletion of cell energy levels will significantly lower the energy demands of electrolyte transport by decreasing chloride conductance. We believe this direct coupling between cellular ATP levels and chloride channel activity is an adaptive mechanism to protect the tissue from damage resulting from excessive energy depletion."} {"id": "PMID:1279437", "title": "The protein kinase A-regulated cardiac Cl- channel resembles the cystic fibrosis transmembrane conductance regulator.", "content": "Stimulation of beta-adrenoceptors in cardiac ventricular myocytes activates a strong chloride ion conductance as a result of phosphorylation by cyclic AMP-dependent protein kinase (PKA). This Cl- conductance, which is time- and voltage-independent, counters the tendency of the simultaneously enhanced Ca2+ channel current to prolong the ventricular action potential. Using inside-out giant patches excised from guinea-pig myocytes, we show here that phosphorylation by the PKA catalytic subunit plus Mg-ATP elicits discrete Cl- channel currents. In almost symmetrical Cl- solutions (approximately 150 mM), unitary current amplitude scales with membrane potential, and reverses sign near 0 mV, to yield a single channel conductance of approximately 12 pS. Opening of the phosphorylated channels requires hydrolysable nucleoside triphosphate, indicating that phosphorylation by PKA is necessary, but not sufficient, for channel activation. The properties of these PKA-regulated cardiac Cl- channels are very similar, if not identical, to those of the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial cell Cl- channel whose regulation is defective in patients with cystic fibrosis. The full cardiological impact of these Cl- channels and of their possible malfunction in patients with cystic fibrosis remains to be determined.", "contents": "The protein kinase A-regulated cardiac Cl- channel resembles the cystic fibrosis transmembrane conductance regulator. Stimulation of beta-adrenoceptors in cardiac ventricular myocytes activates a strong chloride ion conductance as a result of phosphorylation by cyclic AMP-dependent protein kinase (PKA). This Cl- conductance, which is time- and voltage-independent, counters the tendency of the simultaneously enhanced Ca2+ channel current to prolong the ventricular action potential. Using inside-out giant patches excised from guinea-pig myocytes, we show here that phosphorylation by the PKA catalytic subunit plus Mg-ATP elicits discrete Cl- channel currents. In almost symmetrical Cl- solutions (approximately 150 mM), unitary current amplitude scales with membrane potential, and reverses sign near 0 mV, to yield a single channel conductance of approximately 12 pS. Opening of the phosphorylated channels requires hydrolysable nucleoside triphosphate, indicating that phosphorylation by PKA is necessary, but not sufficient, for channel activation. The properties of these PKA-regulated cardiac Cl- channels are very similar, if not identical, to those of the cystic fibrosis transmembrane conductance regulator (CFTR), the epithelial cell Cl- channel whose regulation is defective in patients with cystic fibrosis. The full cardiological impact of these Cl- channels and of their possible malfunction in patients with cystic fibrosis remains to be determined."} {"id": "PMID:1279438", "title": "Engineering galactose-binding activity into a C-type mannose-binding protein.", "content": "Calcium-dependent or C-type carbohydrate-recognition domains are homologous protein modules found in a variety of animal lectins. Selective binding of sugars by these domains is essential for glycoprotein clearance, cell-cell adhesion and pathogen neutralization. Although various C-type carbohydrate-recognition domains share sequence identity ranging from 20 to 55%, their sugar-binding characteristics vary widely. The structure of a mannose-binding carbohydrate-recognition domain in complex with a saccharide ligand suggests that two glutamic acid-asparagine pairs are essential determinants of ligand binding by this domain. In C-type lectins that bind galactose with higher affinity than mannose, one of these pairs is replaced by glutamine-aspartic acid. Here we shift the sequence of the mannose-binding protein to correspond to that found in galactose-binding domains in order to test the importance of these residues in sugar-binding selectivity. This simple switch in the position of a single amide group alters the binding activity of the domain so that galactose becomes the preferred ligand.", "contents": "Engineering galactose-binding activity into a C-type mannose-binding protein. Calcium-dependent or C-type carbohydrate-recognition domains are homologous protein modules found in a variety of animal lectins. Selective binding of sugars by these domains is essential for glycoprotein clearance, cell-cell adhesion and pathogen neutralization. Although various C-type carbohydrate-recognition domains share sequence identity ranging from 20 to 55%, their sugar-binding characteristics vary widely. The structure of a mannose-binding carbohydrate-recognition domain in complex with a saccharide ligand suggests that two glutamic acid-asparagine pairs are essential determinants of ligand binding by this domain. In C-type lectins that bind galactose with higher affinity than mannose, one of these pairs is replaced by glutamine-aspartic acid. Here we shift the sequence of the mannose-binding protein to correspond to that found in galactose-binding domains in order to test the importance of these residues in sugar-binding selectivity. This simple switch in the position of a single amide group alters the binding activity of the domain so that galactose becomes the preferred ligand."} {"id": "PMID:1279439", "title": "Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography.", "content": "The principal protein excreted in male rat urine, urinary alpha 2-globulin and the homologous mouse protein, major urinary protein, have been well characterized, although their functions remain unclear. Male rat urine affects the behaviour and sexual response of female rats, leading to the proposal that rodent urinary proteins are responsible for binding pheromones and their subsequent release from drying urine. Urinary alpha 2-globulin is also involved in hyaline droplet nephropathy, an important toxicological syndrome in male rats resulting from exposure to a number of industrial chemicals and characterized by the accumulation of liganded urinary alpha 2-globulin in lysosomes in the kidney, followed by the induction of renal cancer. We now report the three-dimensional structures of mouse major urinary protein (at 2.4 A resolution) and rat urinary alpha 2-globulin (at 2.8 A resolution). The results corroborate the role of these proteins in pheromone transport and elaborate the structural basis of ligand binding.", "contents": "Pheromone binding to two rodent urinary proteins revealed by X-ray crystallography. The principal protein excreted in male rat urine, urinary alpha 2-globulin and the homologous mouse protein, major urinary protein, have been well characterized, although their functions remain unclear. Male rat urine affects the behaviour and sexual response of female rats, leading to the proposal that rodent urinary proteins are responsible for binding pheromones and their subsequent release from drying urine. Urinary alpha 2-globulin is also involved in hyaline droplet nephropathy, an important toxicological syndrome in male rats resulting from exposure to a number of industrial chemicals and characterized by the accumulation of liganded urinary alpha 2-globulin in lysosomes in the kidney, followed by the induction of renal cancer. We now report the three-dimensional structures of mouse major urinary protein (at 2.4 A resolution) and rat urinary alpha 2-globulin (at 2.8 A resolution). The results corroborate the role of these proteins in pheromone transport and elaborate the structural basis of ligand binding."} {"id": "PMID:1279440", "title": "Crystal structure at 2.8 A resolution of a soluble form of the cell adhesion molecule CD2.", "content": "The crystal structure of a soluble form of the T lymphocyte antigen CD2 provides the first complete view of the extracellular region of a cell adhesion molecule. The topology of the molecule, which comprises two immunoglobulin-like domains, is the same as that of the first two domains of CD4 but the relative domain orientation is altered by a fairly flexible linker region. The putative ligand-binding beta-sheet forms a flat surface towards the top of the molecule. Crystal contacts between these surfaces suggest a plausible model for the adhesive interaction.", "contents": "Crystal structure at 2.8 A resolution of a soluble form of the cell adhesion molecule CD2. The crystal structure of a soluble form of the T lymphocyte antigen CD2 provides the first complete view of the extracellular region of a cell adhesion molecule. The topology of the molecule, which comprises two immunoglobulin-like domains, is the same as that of the first two domains of CD4 but the relative domain orientation is altered by a fairly flexible linker region. The putative ligand-binding beta-sheet forms a flat surface towards the top of the molecule. Crystal contacts between these surfaces suggest a plausible model for the adhesive interaction."} {"id": "PMID:1279441", "title": "GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells.", "content": "Dendritic cells comprise a system of highly efficient antigen-presenting cells which initiate immune responses such as the sensitization of T cells restricted by major histocompatibility complex molecules, the rejection of organ transplants and the formation of T-cell-dependent antibodies. Dendritic cells are found in many non-lymphoid tissues, such as skin (Langerhans cells) and mucosa, and they migrate after antigen capture through the afferent lymph or the bloodstream to lymphoid organs, where they efficiently present antigen to T cells. Dendritic cells are difficult to isolate and, although they originate from bone marrow their site of maturation and the conditions that direct their growth and differentiation are still poorly characterized. Granulocyte macrophage-colony stimulating factor (GM-CSF) favours the outgrowth of dendritic cells from mouse peripheral blood. Here we extend this finding to man and demonstrate that cooperation between GM-CSF and tumour necrosis factor-alpha (TNF-alpha) is crucial for the generation of human dendritic/Langerhans cells from CD34+ haematopoietic progenitors. The availability of large numbers of these cells should now facilitate the understanding of their role in immunological regulation and disorder.", "contents": "GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells. Dendritic cells comprise a system of highly efficient antigen-presenting cells which initiate immune responses such as the sensitization of T cells restricted by major histocompatibility complex molecules, the rejection of organ transplants and the formation of T-cell-dependent antibodies. Dendritic cells are found in many non-lymphoid tissues, such as skin (Langerhans cells) and mucosa, and they migrate after antigen capture through the afferent lymph or the bloodstream to lymphoid organs, where they efficiently present antigen to T cells. Dendritic cells are difficult to isolate and, although they originate from bone marrow their site of maturation and the conditions that direct their growth and differentiation are still poorly characterized. Granulocyte macrophage-colony stimulating factor (GM-CSF) favours the outgrowth of dendritic cells from mouse peripheral blood. Here we extend this finding to man and demonstrate that cooperation between GM-CSF and tumour necrosis factor-alpha (TNF-alpha) is crucial for the generation of human dendritic/Langerhans cells from CD34+ haematopoietic progenitors. The availability of large numbers of these cells should now facilitate the understanding of their role in immunological regulation and disorder."} {"id": "PMID:1279442", "title": "Signalling through the MHC class II cytoplasmic domain is required for antigen presentation and induces B7 expression.", "content": "Class II major histocompatibility complex (MHC) molecules function as antigen-presenting elements as well as signal transducers on B lymphocytes. We previously reported that a B lymphoma cell transfectant, 5C2, expressing genetically engineered I-Ak molecules with truncated cytoplasmic domains was severely impaired in both antigen presentation and in anti-Ia-induced intracytoplasmic signalling. These two functions could be restored by preculturing 5C2 cells with cyclic AMP analogues. Here we demonstrate that impaired signal transduction by truncated class II molecules results in a deficiency in induction of the newly defined B-cell accessory molecule B7 (ref. 8), which can be reversed by restoration of B7 expression. These data imply that contact of the T-cell antigen receptor with MHC/antigen ligand results in signal transmission through the class II cytoplasmic domain. This signal, which can be mimicked by dibutyryl cAMP, induces expression of B7, resulting in effective antigen presentation. The fact that crosslinking of surface class II MHC also induces B7 expression on normal resting human B cells supports this contention.", "contents": "Signalling through the MHC class II cytoplasmic domain is required for antigen presentation and induces B7 expression. Class II major histocompatibility complex (MHC) molecules function as antigen-presenting elements as well as signal transducers on B lymphocytes. We previously reported that a B lymphoma cell transfectant, 5C2, expressing genetically engineered I-Ak molecules with truncated cytoplasmic domains was severely impaired in both antigen presentation and in anti-Ia-induced intracytoplasmic signalling. These two functions could be restored by preculturing 5C2 cells with cyclic AMP analogues. Here we demonstrate that impaired signal transduction by truncated class II molecules results in a deficiency in induction of the newly defined B-cell accessory molecule B7 (ref. 8), which can be reversed by restoration of B7 expression. These data imply that contact of the T-cell antigen receptor with MHC/antigen ligand results in signal transmission through the class II cytoplasmic domain. This signal, which can be mimicked by dibutyryl cAMP, induces expression of B7, resulting in effective antigen presentation. The fact that crosslinking of surface class II MHC also induces B7 expression on normal resting human B cells supports this contention."} {"id": "PMID:1279445", "title": "Streptozotocin-induced decreases in serotonin turnover are prevented by thyroidectomy.", "content": "Although characterized as hypothyroid, streptozotocin-diabetic rats have reduced serotonin turnover (5-hydroxyindoleacetic acid/serotonin, 5-HIAA/5-HT) in brain stem, while hypothyroid rats have increased 5-HIAA/5-HT. In the present study the two treatments were combined to determine if they affected 5-HIAA/5-HT through the same mechanism. In addition, an alternative method was used to assess 5-HT activity in thyroidectomized (TX) rats, i.e. measurement of 5-HT disappearance after inhibition of tryptophan hydroxylase with p-chlorophenylalanine (PCPA). Adult male rats were first TX (experiment 1) or given methimazole (METH; experiment 3). Two weeks later, diabetes (DB) was induced with streptozotocin in hypothyroid rats and euthyroid controls. Two weeks later, functional measurements were taken. Rats were then killed, and spinal cord and brain stem serotonin turnover (5-HIAA/5-HT), as well as plasma T3, T4 and corticosterone (CORT) concentrations were measured. TX attenuated diabetic hyperphagia and weight loss. DB alone led to moderate reductions in T3 and T4, but the hormones were barely detectable in plasma of TX and METH rats. CORT was elevated in DB but was not affected by TX. Open field activity was not affected by DB or TX. TX and METH significantly increased 5-HIAA/5-HT in both spinal cord and brain stem. TX also led to enhanced disappearance of 5-HT after PCPA. DB significantly reduced 5-HIAA/5-HT, suggesting independent effects of the treatments. However, DB-TX rats still had significantly higher 5-HIAA/5-HT than control-sham surgery rats, while DB-METH rats had 5-HIAA/5-HT indistinguishable from controls. In both cases, prior induction of primary hypothyroidism interfered with the expected diabetes-induced reduction in 5-HT turnover.", "contents": "Streptozotocin-induced decreases in serotonin turnover are prevented by thyroidectomy. Although characterized as hypothyroid, streptozotocin-diabetic rats have reduced serotonin turnover (5-hydroxyindoleacetic acid/serotonin, 5-HIAA/5-HT) in brain stem, while hypothyroid rats have increased 5-HIAA/5-HT. In the present study the two treatments were combined to determine if they affected 5-HIAA/5-HT through the same mechanism. In addition, an alternative method was used to assess 5-HT activity in thyroidectomized (TX) rats, i.e. measurement of 5-HT disappearance after inhibition of tryptophan hydroxylase with p-chlorophenylalanine (PCPA). Adult male rats were first TX (experiment 1) or given methimazole (METH; experiment 3). Two weeks later, diabetes (DB) was induced with streptozotocin in hypothyroid rats and euthyroid controls. Two weeks later, functional measurements were taken. Rats were then killed, and spinal cord and brain stem serotonin turnover (5-HIAA/5-HT), as well as plasma T3, T4 and corticosterone (CORT) concentrations were measured. TX attenuated diabetic hyperphagia and weight loss. DB alone led to moderate reductions in T3 and T4, but the hormones were barely detectable in plasma of TX and METH rats. CORT was elevated in DB but was not affected by TX. Open field activity was not affected by DB or TX. TX and METH significantly increased 5-HIAA/5-HT in both spinal cord and brain stem. TX also led to enhanced disappearance of 5-HT after PCPA. DB significantly reduced 5-HIAA/5-HT, suggesting independent effects of the treatments. However, DB-TX rats still had significantly higher 5-HIAA/5-HT than control-sham surgery rats, while DB-METH rats had 5-HIAA/5-HT indistinguishable from controls. In both cases, prior induction of primary hypothyroidism interfered with the expected diabetes-induced reduction in 5-HT turnover."} {"id": "PMID:1279446", "title": "Oxytocin nerve fibers innervate beta-endorphin neurons in the arcuate nucleus of the rat hypothalamus.", "content": "Fine, varicose oxytocin-containing nerve fibers have been demonstrated in the hypothalamic arcuate nucleus in rats. Using Phaseolus vulgaris leukoagglutinin as an anterograde tracer, fine neuronal fibers of paraventricular nucleus origin could be seen throughout the arcuate nucleus. Using double immunostaining, oxytocin-immunoreactive varicose fibers were observed around or in the close vicinity of beta-endorphin-immunoreactive neurons. Silver-gold-labeled oxytocin-immunoreactive presynaptic boutons were shown to make synaptic contacts with diaminobenzidine-labeled beta-endorphin-immunoreactive neurons by electron microscopy. These findings provide morphological evidence for a possible influence of oxytocin on the activity of the brain beta-endorphin system at the hypothalamic level.", "contents": "Oxytocin nerve fibers innervate beta-endorphin neurons in the arcuate nucleus of the rat hypothalamus. Fine, varicose oxytocin-containing nerve fibers have been demonstrated in the hypothalamic arcuate nucleus in rats. Using Phaseolus vulgaris leukoagglutinin as an anterograde tracer, fine neuronal fibers of paraventricular nucleus origin could be seen throughout the arcuate nucleus. Using double immunostaining, oxytocin-immunoreactive varicose fibers were observed around or in the close vicinity of beta-endorphin-immunoreactive neurons. Silver-gold-labeled oxytocin-immunoreactive presynaptic boutons were shown to make synaptic contacts with diaminobenzidine-labeled beta-endorphin-immunoreactive neurons by electron microscopy. These findings provide morphological evidence for a possible influence of oxytocin on the activity of the brain beta-endorphin system at the hypothalamic level."} {"id": "PMID:1279447", "title": "Comparison of norfluoxetine enantiomers as serotonin uptake inhibitors in vivo.", "content": "Norfluoxetine, the N-desmethyl metabolite of fluoxetine, has been reported to resemble fluoxetine in being a potent and selective inhibitor of the serotonin uptake carrier. The enantiomers of norfluoxetine have now been compared as serotonin uptake inhibitors in vivo, based on their antagonism of p-chloroamphetamine-induced depletion of serotonin in brain and their lowering of concentrations of the metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA) in brain. In rats, S-norfluoxetine (ED50 3.8 mg/kg) was more potent than R-norfluoxetine (ED50 > 20 mg/kg) in blocking the depletion of serotonin by p-chloroamphetamine after intraperitoneal administration. The S enantiomer decreased concentrations of 5-HIAA in whole brain after doses of 2.5-20 mg/kg, whereas the R enantiomer did not. The concentrations of both enantiomers in brain increased in proportion to dose and the R enantiomer disappeared from the brain at a slightly slower rate than the S enantiomer. The relative inability of the R enantiomer to block the uptake of serotonin was therefore not a result of smaller concentrations of drug in the brain. In mice, S-norfluoxetine was also more potent than R-norfluoxetine in blocking depletion of serotonin by p-chloroamphetamine (ED50 values 0.82 and 8.3 mg/kg, respectively). Thus, in contrast to the relatively similar potencies of the enantiomers of fluoxetine in blocking the uptake of serotonin, the enantiomers of norfluoxetine have markedly different potencies as inhibitors of the uptake of serotonin.", "contents": "Comparison of norfluoxetine enantiomers as serotonin uptake inhibitors in vivo. Norfluoxetine, the N-desmethyl metabolite of fluoxetine, has been reported to resemble fluoxetine in being a potent and selective inhibitor of the serotonin uptake carrier. The enantiomers of norfluoxetine have now been compared as serotonin uptake inhibitors in vivo, based on their antagonism of p-chloroamphetamine-induced depletion of serotonin in brain and their lowering of concentrations of the metabolite of serotonin, 5-hydroxyindoleacetic acid (5-HIAA) in brain. In rats, S-norfluoxetine (ED50 3.8 mg/kg) was more potent than R-norfluoxetine (ED50 > 20 mg/kg) in blocking the depletion of serotonin by p-chloroamphetamine after intraperitoneal administration. The S enantiomer decreased concentrations of 5-HIAA in whole brain after doses of 2.5-20 mg/kg, whereas the R enantiomer did not. The concentrations of both enantiomers in brain increased in proportion to dose and the R enantiomer disappeared from the brain at a slightly slower rate than the S enantiomer. The relative inability of the R enantiomer to block the uptake of serotonin was therefore not a result of smaller concentrations of drug in the brain. In mice, S-norfluoxetine was also more potent than R-norfluoxetine in blocking depletion of serotonin by p-chloroamphetamine (ED50 values 0.82 and 8.3 mg/kg, respectively). Thus, in contrast to the relatively similar potencies of the enantiomers of fluoxetine in blocking the uptake of serotonin, the enantiomers of norfluoxetine have markedly different potencies as inhibitors of the uptake of serotonin."} {"id": "PMID:1279448", "title": "The effect of 3,3-di-pyridyl-methyl-1-phenyl-2-indolinone on the nerve terminal currents of mouse skeletal muscles.", "content": "The effects of 3,3-dipyridyl-methyl-1-phenyl-2-indolinone (DPMPI), a new cognition enhancer, on perineural waveforms were assessed on triangularis sterni nerve-muscle preparations in the mouse. The perineural waveforms were recorded with extracellular electrodes placed in the perineural sheaths of motor nerves. At 64.5 microM, DPMPI decreased the fast potassium current of the nerve terminal. The sodium current, calcium currents and calcium-dependent potassium current of the nerve terminal were not affected. At a greater concentration (215 microM), DPMPI decreased all of the components of the waveforms associated with sodium, potassium and calcium currents. It is concluded that DPMPI affects potassium, as well as sodium currents in the nerve terminal. The effect may contribute to its pharmacological actions on synaptic transmission.", "contents": "The effect of 3,3-di-pyridyl-methyl-1-phenyl-2-indolinone on the nerve terminal currents of mouse skeletal muscles. The effects of 3,3-dipyridyl-methyl-1-phenyl-2-indolinone (DPMPI), a new cognition enhancer, on perineural waveforms were assessed on triangularis sterni nerve-muscle preparations in the mouse. The perineural waveforms were recorded with extracellular electrodes placed in the perineural sheaths of motor nerves. At 64.5 microM, DPMPI decreased the fast potassium current of the nerve terminal. The sodium current, calcium currents and calcium-dependent potassium current of the nerve terminal were not affected. At a greater concentration (215 microM), DPMPI decreased all of the components of the waveforms associated with sodium, potassium and calcium currents. It is concluded that DPMPI affects potassium, as well as sodium currents in the nerve terminal. The effect may contribute to its pharmacological actions on synaptic transmission."} {"id": "PMID:1279449", "title": "Substance P augments the rate of vasodilation induced by calcitonin gene-related peptide in porcine ophthalmic artery in vitro.", "content": "Peptides may function as neurotransmitters liberated antidromically by sensory nerve fibres, provoking vascular responses having potential importance in some neurological disorders. Dose-response relaxation curves induced by substance P (SP) and calcitonin gene related peptide (CGRP) have been studied in porcine ophthalmic arteries in vitro. Both peptides induced vasodilation when tested separately (CGRP much greater than SP). Because of the putative interactions between such peptides in this vascular territory, a computerised system was also used for analysing over time the response to a single addition of either 10(-8) M CGRP, 10(-8) M SP or a combination of 10(-8) M SP + 10(-8) M CGRP. SP did not augment the maximum relaxation induced by CGRP alone, but increased significantly the rate of relaxation during the initial phase of the response. The effect induced by the SP+CGRP combination was stronger than the sum of the individual SP and CGRP-induced relaxations during the first 4 min of the response, which suggests a SP-CGRP synergism in this artery.", "contents": "Substance P augments the rate of vasodilation induced by calcitonin gene-related peptide in porcine ophthalmic artery in vitro. Peptides may function as neurotransmitters liberated antidromically by sensory nerve fibres, provoking vascular responses having potential importance in some neurological disorders. Dose-response relaxation curves induced by substance P (SP) and calcitonin gene related peptide (CGRP) have been studied in porcine ophthalmic arteries in vitro. Both peptides induced vasodilation when tested separately (CGRP much greater than SP). Because of the putative interactions between such peptides in this vascular territory, a computerised system was also used for analysing over time the response to a single addition of either 10(-8) M CGRP, 10(-8) M SP or a combination of 10(-8) M SP + 10(-8) M CGRP. SP did not augment the maximum relaxation induced by CGRP alone, but increased significantly the rate of relaxation during the initial phase of the response. The effect induced by the SP+CGRP combination was stronger than the sum of the individual SP and CGRP-induced relaxations during the first 4 min of the response, which suggests a SP-CGRP synergism in this artery."} {"id": "PMID:1279450", "title": "Peptidergic modulation of G-protein coupled cyclic-AMP accumulation in the rat caudate nucleus.", "content": "Somatostatin, substance P, and vasoactive intestinal polypeptide were incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the neuropeptides on G-protein coupled adenylate cyclase in vitro. Somatostatin induced an enhancement of cyclic AMP formation in presence of guanine nucleotides and cholera toxin but inhibited pertussis toxin and forskolin enzyme stimulation. Pertussis toxin and cholera toxin also depressed forskolin-induced stimulation as described previously. Somatostatin was able to antagonize these inhibitory effects of both toxins. On the contrary, substance P reduced GTP and cholera toxin stimulated striatal adenylate cyclase, without affecting forskolin activation. In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by guanine nucleotides, cholera toxin, and pertussis toxin. VIP potently inhibited the enhancement of cyclic AMP formation by forskolin and completely antagonized the inhibitory effect of cholera toxin on forskolin activation. These results suggest that neuromodulatory effects of somatostatin, substance P, and VIP are mediated by the inhibitory as well as stimulatory guanine nucleotide proteins G-i and G-s coupled to an adenylate cyclase system.", "contents": "Peptidergic modulation of G-protein coupled cyclic-AMP accumulation in the rat caudate nucleus. Somatostatin, substance P, and vasoactive intestinal polypeptide were incubated in an adenylate cyclase assay with a particulate fraction of caudate-putamen tissue of the rat in order to examine the effect of the neuropeptides on G-protein coupled adenylate cyclase in vitro. Somatostatin induced an enhancement of cyclic AMP formation in presence of guanine nucleotides and cholera toxin but inhibited pertussis toxin and forskolin enzyme stimulation. Pertussis toxin and cholera toxin also depressed forskolin-induced stimulation as described previously. Somatostatin was able to antagonize these inhibitory effects of both toxins. On the contrary, substance P reduced GTP and cholera toxin stimulated striatal adenylate cyclase, without affecting forskolin activation. In our preparation, VIP did not influence basal adenylate cyclase activity or the stimulation by guanine nucleotides, cholera toxin, and pertussis toxin. VIP potently inhibited the enhancement of cyclic AMP formation by forskolin and completely antagonized the inhibitory effect of cholera toxin on forskolin activation. These results suggest that neuromodulatory effects of somatostatin, substance P, and VIP are mediated by the inhibitory as well as stimulatory guanine nucleotide proteins G-i and G-s coupled to an adenylate cyclase system."} {"id": "PMID:1279451", "title": "Management outcome for vertebrobasilar artery aneurysms by early surgery.", "content": "Treatment of vertebrobasilar artery aneurysms remains fraught with complications, even in the present era of microneurosurgery. In a series of 1150 consecutive patients with cerebral aneurysms from a defined catchment area with 870,000 inhabitants, 93 with vertebrobasilar artery aneurysms were treated by two surgeons during a 14-year period. Sixty-three patients had surgery, 36 during the first week after bleeding. There was no surgical mortality among 33 good grade patients. Nine (14%) of the 63 surgical cases had died at 1 year. Forty-nine (53%) of the total group of 93 patients were functioning independently at 1 year. Overall management mortality was 37%. All 11 patients admitted in Grade V died. In spite of improvements in surgical techniques, we are far from achieving ideal results. Early diagnosis and surgery before rupture are urgently needed. Arteriosclerotic giant aneurysms remain untreatable.", "contents": "Management outcome for vertebrobasilar artery aneurysms by early surgery. Treatment of vertebrobasilar artery aneurysms remains fraught with complications, even in the present era of microneurosurgery. In a series of 1150 consecutive patients with cerebral aneurysms from a defined catchment area with 870,000 inhabitants, 93 with vertebrobasilar artery aneurysms were treated by two surgeons during a 14-year period. Sixty-three patients had surgery, 36 during the first week after bleeding. There was no surgical mortality among 33 good grade patients. Nine (14%) of the 63 surgical cases had died at 1 year. Forty-nine (53%) of the total group of 93 patients were functioning independently at 1 year. Overall management mortality was 37%. All 11 patients admitted in Grade V died. In spite of improvements in surgical techniques, we are far from achieving ideal results. Early diagnosis and surgery before rupture are urgently needed. Arteriosclerotic giant aneurysms remain untreatable."} {"id": "PMID:1279452", "title": "The expression of the immediate-early genes c-fos, egr-1 and c-jun in the accessory olfactory bulb during the formation of an olfactory memory in mice.", "content": "Female mice form a memory for the pheromones of the male with which they mate. It has been proposed that the site of the synaptic changes underlying this memory is the accessory olfactory bulb, at the first level of the accessory olfactory system. In this study we have examined the expression of the immediate-early genes c-fos, c-jun and egr-1 in the mitral and granule cells of the accessory olfactory bulb immediately after mating, during the period of memory formation. Transient increases were seen in the number of granule cell nuclei expressing c-fos and the number of granule and mitral cell nuclei expressing egr-1, during the period of memory formation. No changes were observed in the expression of c-jun during this period. The increase in the number of cells expressing c-fos and egr-1 required the association of mating and pheromonal exposure, conditions also required for memory formation. Large increases in the number of mitral and granule cell nuclei expressing c-fos and egr-1 were also observed following the infusion of the drug bicuculline into the accessory olfactory bulb in the absence of mating. This procedure has previously been shown to result in the formation of a nonspecific memory for male pheromones. These results associate the expression of c-fos and egr-1 in the accessory olfactory bulb with the conditions required for the formation of an olfactory memory for male pheromones.", "contents": "The expression of the immediate-early genes c-fos, egr-1 and c-jun in the accessory olfactory bulb during the formation of an olfactory memory in mice. Female mice form a memory for the pheromones of the male with which they mate. It has been proposed that the site of the synaptic changes underlying this memory is the accessory olfactory bulb, at the first level of the accessory olfactory system. In this study we have examined the expression of the immediate-early genes c-fos, c-jun and egr-1 in the mitral and granule cells of the accessory olfactory bulb immediately after mating, during the period of memory formation. Transient increases were seen in the number of granule cell nuclei expressing c-fos and the number of granule and mitral cell nuclei expressing egr-1, during the period of memory formation. No changes were observed in the expression of c-jun during this period. The increase in the number of cells expressing c-fos and egr-1 required the association of mating and pheromonal exposure, conditions also required for memory formation. Large increases in the number of mitral and granule cell nuclei expressing c-fos and egr-1 were also observed following the infusion of the drug bicuculline into the accessory olfactory bulb in the absence of mating. This procedure has previously been shown to result in the formation of a nonspecific memory for male pheromones. These results associate the expression of c-fos and egr-1 in the accessory olfactory bulb with the conditions required for the formation of an olfactory memory for male pheromones."} {"id": "PMID:1279453", "title": "Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat.", "content": "Immunohistological and in situ hybridization techniques were used to study the influence of kainic acid-induced seizures and of pentylenetetrazol kindling on neurokinin B immunoreactivity and neurokinin B mRNA in the rat hippocampus. Pronounced increases in neurokinin B immunoreactivity were observed in the terminal field of mossy fibres 10-60 days after intraperitoneal injection of kainic acid. These slow but persistent increases in immunoreactivity were accompanied by markedly enhanced expression of neurokinin B mRNA in the granule cells and in hilar interneurons adjacent to the granule cell layer. These changes were preceded by transient increases in neurokinin B mRNA and immunoreactivity in CA1 pyramidal cell layer two and 10 days after kainic acid, which, however, subsided later on. Pentylenetetrazol kindling caused similar increases in neurokinin B mRNA expression in granule cells and in CA1 pyramidal cells, but not in hilar interneurons. In CA1, increased neurokinin B message was present two days after termination of the kindling procedure but not after 10 days. Sixty days after kainic acid injection, neurokinin B immunoreactivity extended to the inner-third of the molecular layer of the dentate gyrus. After pentylenetetrazol kindling, a neurokinin B-immunoreactive band was observed in the infrapyramidal region of CA3. Lesions of the dentate granule cells by local injection of colchicine in kainic acid-treated rats abolished the supragranular neurokinin B-positive staining, whereas it was almost unchanged after transection of the ventral hippocampal commissure. These observations suggest that neurokinin B immunoreactivity may be located in ipsilateral mossy fibres undergoing collateral sprouting to the inner molecular layer or to the infrapyramidal region in CA3, respectively. Preprotachykinin A mRNA, which encodes for neurokinin A and substance P, and substance P immunoreactivity were not changed in the hippocampus of epileptic rats compared with untreated animals. The observed changes in neurokinin B immunoreactivity and mRNA indicate that specific functional and morphological changes may be induced in hippocampal neurons by recurrent limbic seizures.", "contents": "Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat. Immunohistological and in situ hybridization techniques were used to study the influence of kainic acid-induced seizures and of pentylenetetrazol kindling on neurokinin B immunoreactivity and neurokinin B mRNA in the rat hippocampus. Pronounced increases in neurokinin B immunoreactivity were observed in the terminal field of mossy fibres 10-60 days after intraperitoneal injection of kainic acid. These slow but persistent increases in immunoreactivity were accompanied by markedly enhanced expression of neurokinin B mRNA in the granule cells and in hilar interneurons adjacent to the granule cell layer. These changes were preceded by transient increases in neurokinin B mRNA and immunoreactivity in CA1 pyramidal cell layer two and 10 days after kainic acid, which, however, subsided later on. Pentylenetetrazol kindling caused similar increases in neurokinin B mRNA expression in granule cells and in CA1 pyramidal cells, but not in hilar interneurons. In CA1, increased neurokinin B message was present two days after termination of the kindling procedure but not after 10 days. Sixty days after kainic acid injection, neurokinin B immunoreactivity extended to the inner-third of the molecular layer of the dentate gyrus. After pentylenetetrazol kindling, a neurokinin B-immunoreactive band was observed in the infrapyramidal region of CA3. Lesions of the dentate granule cells by local injection of colchicine in kainic acid-treated rats abolished the supragranular neurokinin B-positive staining, whereas it was almost unchanged after transection of the ventral hippocampal commissure. These observations suggest that neurokinin B immunoreactivity may be located in ipsilateral mossy fibres undergoing collateral sprouting to the inner molecular layer or to the infrapyramidal region in CA3, respectively. Preprotachykinin A mRNA, which encodes for neurokinin A and substance P, and substance P immunoreactivity were not changed in the hippocampus of epileptic rats compared with untreated animals. The observed changes in neurokinin B immunoreactivity and mRNA indicate that specific functional and morphological changes may be induced in hippocampal neurons by recurrent limbic seizures."} {"id": "PMID:1279454", "title": "Mapping of the motor pathways in rats: c-fos induction by intracortical microstimulation of the motor cortex correlated with efferent connectivity of the site of cortical stimulation.", "content": "The general goal of the present study was to investigate structural components of a neural system anatomically as well as functionally. The rat motor system, which is reasonably well understood, was selected and a new procedure was developed to combine a functional marker with axonal tracing methods (in the same animal). This was achieved by mapping c-fos induction immunocytochemically as a result of intracortical microstimulation in the distal forelimb area of the motor cortex. The anterograde tracers Phaseolus vulgaris-leucoagglutinin or biocytin were deposited at the site of intracortical microstimulation, the former three weeks and the latter two to three days before stimulation. Neuronal nuclei, labeled for the expressed c-fos protein, were present and mapped in the following structures: motor cortex; basal ganglia (caudate-putamen, globus pallidus); thalamus (reticular, ventromedial and posterior nuclei); subthalamic nucleus; substantia nigra; tectum; red nucleus; pontine nuclei; inferior olive; external cuneate nucleus; cerebellar cortex; deep cerebellar nuclei. Labeling was often bilateral but generally more substantial ipsilaterally, except in the cerebellum where it was mainly contralateral. Axonal labeling, including terminal branches and boutons, was also found in most of the above structures with the exception of the globus pallidus, deep cerebellar nuclei, cerebellar cortex and external cuneate nucleus. These expected exceptions demonstrate that activity changes in these latter structures, as revealed by c-fos labeled neurons, were induced over more than one synapse. This combined procedure might, therefore, be useful in deciding whether two structures in a given system are linked directly (monosynaptically) or indirectly (polysynaptically) to each other. In contrast to the 2-deoxyglucose technique, functional mapping by means of c-fos induction provides cellular resolution, making it possible to establish fine details of axonal contacts with target neurons: boutons in close apposition to c-fos labeled neurons were clearly observed here, for instance in the cerebral cortex, caudate-putamen, thalamus, subthalamic nucleus and pontine nuclei. Surprisingly, the ventrolateral and ventrobasalis nuclei of the thalamus contained numerous and dense axon terminals labeled with Phaseolus vulgaris-leucoagglutinin or biocytin, but the contacted neurons in the ventrolateral and ventrobasalis nuclei were not marked with c-fos. However, with respect to directly connected structures, there was, in general, a good correlation between structures with axonal labeling and those with c-fos labeled neurons.", "contents": "Mapping of the motor pathways in rats: c-fos induction by intracortical microstimulation of the motor cortex correlated with efferent connectivity of the site of cortical stimulation. The general goal of the present study was to investigate structural components of a neural system anatomically as well as functionally. The rat motor system, which is reasonably well understood, was selected and a new procedure was developed to combine a functional marker with axonal tracing methods (in the same animal). This was achieved by mapping c-fos induction immunocytochemically as a result of intracortical microstimulation in the distal forelimb area of the motor cortex. The anterograde tracers Phaseolus vulgaris-leucoagglutinin or biocytin were deposited at the site of intracortical microstimulation, the former three weeks and the latter two to three days before stimulation. Neuronal nuclei, labeled for the expressed c-fos protein, were present and mapped in the following structures: motor cortex; basal ganglia (caudate-putamen, globus pallidus); thalamus (reticular, ventromedial and posterior nuclei); subthalamic nucleus; substantia nigra; tectum; red nucleus; pontine nuclei; inferior olive; external cuneate nucleus; cerebellar cortex; deep cerebellar nuclei. Labeling was often bilateral but generally more substantial ipsilaterally, except in the cerebellum where it was mainly contralateral. Axonal labeling, including terminal branches and boutons, was also found in most of the above structures with the exception of the globus pallidus, deep cerebellar nuclei, cerebellar cortex and external cuneate nucleus. These expected exceptions demonstrate that activity changes in these latter structures, as revealed by c-fos labeled neurons, were induced over more than one synapse. This combined procedure might, therefore, be useful in deciding whether two structures in a given system are linked directly (monosynaptically) or indirectly (polysynaptically) to each other. In contrast to the 2-deoxyglucose technique, functional mapping by means of c-fos induction provides cellular resolution, making it possible to establish fine details of axonal contacts with target neurons: boutons in close apposition to c-fos labeled neurons were clearly observed here, for instance in the cerebral cortex, caudate-putamen, thalamus, subthalamic nucleus and pontine nuclei. Surprisingly, the ventrolateral and ventrobasalis nuclei of the thalamus contained numerous and dense axon terminals labeled with Phaseolus vulgaris-leucoagglutinin or biocytin, but the contacted neurons in the ventrolateral and ventrobasalis nuclei were not marked with c-fos. However, with respect to directly connected structures, there was, in general, a good correlation between structures with axonal labeling and those with c-fos labeled neurons."} {"id": "PMID:1279455", "title": "Calbindin D28k-containing nonpyramidal cells in the rat hippocampus: their immunoreactivity for GABA and projection to the medial septum.", "content": "Calbindin D28k-containing non-pyramidal cells were found in all layers and subfields of the hippocampus, with the highest frequency in stratum radiatum of the CA1-CA3 subfields. A large number of these neurons had a vertically oriented dendritic tree, often restricted to to stratum radiatum. In stratum oriens and near to the border of strata radiatum and lacunosum moleculare cells with horizontally running dendrites were also found. Multipolar cells were most common in stratum radiatum of the CA3 region. The GABAergic nature of the calbindin D28k-containing non-pyramidal cells was studied using the \"mirror\" technique. Adjacent thick sections were immunostained for calbindin D28k and GABA, and halved neurons were identified on the common surfaces. The majority of calbindin D28k-containing non-pyramidal cells were shown to be GABAergic. The GABA-negative calbindin cells were found in relatively large numbers in stratum oriens of the CA1-CA3 region, and occasionally in strata radiatum and pyramidale of CA2, and in stratum radiatum of the CA3c region near to the border of the dentate hilus. However, even in these cells a weak immunostaining, only slightly but consistently above background level, was always observed. Earlier studies have demonstrated that the somata of GABAergic neurons with distant projections may contain a level of GABA that is below the detection threshold of immunocytochemistry. Here we provide direct evidence that the calbindin-containing non-pyramidal cells were among those projecting to the medial septum. Following horseradish peroxidase injections into the medial septum 80% of the retrogradely labelled non-pyramidal cells were found to be immunoreactive for calbindin D28k, and 20% contained neuropeptide Y. These results suggest that the calbindin D28k-containing and apparently GABA-immunonegative non-pyramidal cells in stratum oriens of the CA1-CA3 regions may also be GABAergic, but have a distant projection, that is, to the medial septum.", "contents": "Calbindin D28k-containing nonpyramidal cells in the rat hippocampus: their immunoreactivity for GABA and projection to the medial septum. Calbindin D28k-containing non-pyramidal cells were found in all layers and subfields of the hippocampus, with the highest frequency in stratum radiatum of the CA1-CA3 subfields. A large number of these neurons had a vertically oriented dendritic tree, often restricted to to stratum radiatum. In stratum oriens and near to the border of strata radiatum and lacunosum moleculare cells with horizontally running dendrites were also found. Multipolar cells were most common in stratum radiatum of the CA3 region. The GABAergic nature of the calbindin D28k-containing non-pyramidal cells was studied using the \"mirror\" technique. Adjacent thick sections were immunostained for calbindin D28k and GABA, and halved neurons were identified on the common surfaces. The majority of calbindin D28k-containing non-pyramidal cells were shown to be GABAergic. The GABA-negative calbindin cells were found in relatively large numbers in stratum oriens of the CA1-CA3 region, and occasionally in strata radiatum and pyramidale of CA2, and in stratum radiatum of the CA3c region near to the border of the dentate hilus. However, even in these cells a weak immunostaining, only slightly but consistently above background level, was always observed. Earlier studies have demonstrated that the somata of GABAergic neurons with distant projections may contain a level of GABA that is below the detection threshold of immunocytochemistry. Here we provide direct evidence that the calbindin-containing non-pyramidal cells were among those projecting to the medial septum. Following horseradish peroxidase injections into the medial septum 80% of the retrogradely labelled non-pyramidal cells were found to be immunoreactive for calbindin D28k, and 20% contained neuropeptide Y. These results suggest that the calbindin D28k-containing and apparently GABA-immunonegative non-pyramidal cells in stratum oriens of the CA1-CA3 regions may also be GABAergic, but have a distant projection, that is, to the medial septum."} {"id": "PMID:1279456", "title": "Regional stimulatory and inhibitory effects of guanine nucleotides on [125I]galanin binding in rat brain: relationship with the rate of occupancy of galanin receptors by endogenous galanin.", "content": "Galanin has been shown to stimulate feeding or modulate neuroendocrine secretions when administered centrally. In the present work, using quantitative autoradiography, we documented the existence of [125I]galanin specific binding sites in several hypothalamic nuclei expected to mediate these effects. In standard binding conditions, [125I]galanin specific binding can be visualized in the hypothalamic ventromedial nucleus, stria terminalis, piriform cortex, central amygdaloid nucleus and medial amygdaloid nucleus, while it is almost undetectable in most neuroendocrine or autonomic hypothalamic areas. We hypothesized that high endogenous galanin levels in these regions might mask galanin receptors. We first showed that a high ionic strength/acid wash of brain slices is effective in removing more than 80% of specifically prebound [125I]galanin in all tested regions. After such treatments, specific binding sites could be revealed in the hypothalamus namely in the parvocellular paraventricular nucleus, periventricular nucleus, arcuate nucleus and median eminence. In contrast, regions already labeled in standard conditions exhibited a slight decrease in [125I]galanin binding. Thus, regions were ranked from low to high rate of occupancy of galanin receptors by endogenous galanin, the rate of occupancy of galanin receptors being maximal in median eminence (greater than 90%). We thus studied the regional effect of guanine nucleotides on [125I]galanin specific binding. A high concentration (100 microM) of guanyl 5'-yl imidodiphosphate, a nonhydrolyzable analog of GTP directly added to the incubation medium, inhibited [125I]galanin binding in all telencephalic regions. On the same sections and only in regions of high index of galanin receptor occupancy (arcuate nucleus, median eminence, dorsomedial nucleus, paraventricular nucleus, and periventricular hypothalamic nucleus), guanyl 5'-yl imidodiphosphate paradoxically enhanced [125I]galanin binding. The effects of acid preincubation and guanyl 5'-yl imidodiphosphate incubation on [125I]galanin binding were strongly correlated in these hypothalamic areas (r = 0.97). In all regions, guanyl 5'-yl imidodiphosphate increased the rate of dissociation of [125I]galanin. In competition studies, guanyl 5'-yl imidodiphosphate decreased the IC50 s of unlabeled galanin which were homogenized around 4 nM in most telencephalic and hypothalamic regions. Thus, the guanyl 5'-yl imidodiphosphate-induced stimulation of [125I]galanin specific binding measured in the neuroendocrine and autonomic hypothalamus is linked to an increase in receptor capacity and not to a rise in receptor affinity. Both inhibitory and stimulatory guanyl 5'-yl imidodiphosphate effects observed in [125I]galanin equilibrium binding studies were dose-dependent and guanine nucleotide-specific with guanyl 5'-yl imidodiphosphate more potent than GTP or GDP.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Regional stimulatory and inhibitory effects of guanine nucleotides on [125I]galanin binding in rat brain: relationship with the rate of occupancy of galanin receptors by endogenous galanin. Galanin has been shown to stimulate feeding or modulate neuroendocrine secretions when administered centrally. In the present work, using quantitative autoradiography, we documented the existence of [125I]galanin specific binding sites in several hypothalamic nuclei expected to mediate these effects. In standard binding conditions, [125I]galanin specific binding can be visualized in the hypothalamic ventromedial nucleus, stria terminalis, piriform cortex, central amygdaloid nucleus and medial amygdaloid nucleus, while it is almost undetectable in most neuroendocrine or autonomic hypothalamic areas. We hypothesized that high endogenous galanin levels in these regions might mask galanin receptors. We first showed that a high ionic strength/acid wash of brain slices is effective in removing more than 80% of specifically prebound [125I]galanin in all tested regions. After such treatments, specific binding sites could be revealed in the hypothalamus namely in the parvocellular paraventricular nucleus, periventricular nucleus, arcuate nucleus and median eminence. In contrast, regions already labeled in standard conditions exhibited a slight decrease in [125I]galanin binding. Thus, regions were ranked from low to high rate of occupancy of galanin receptors by endogenous galanin, the rate of occupancy of galanin receptors being maximal in median eminence (greater than 90%). We thus studied the regional effect of guanine nucleotides on [125I]galanin specific binding. A high concentration (100 microM) of guanyl 5'-yl imidodiphosphate, a nonhydrolyzable analog of GTP directly added to the incubation medium, inhibited [125I]galanin binding in all telencephalic regions. On the same sections and only in regions of high index of galanin receptor occupancy (arcuate nucleus, median eminence, dorsomedial nucleus, paraventricular nucleus, and periventricular hypothalamic nucleus), guanyl 5'-yl imidodiphosphate paradoxically enhanced [125I]galanin binding. The effects of acid preincubation and guanyl 5'-yl imidodiphosphate incubation on [125I]galanin binding were strongly correlated in these hypothalamic areas (r = 0.97). In all regions, guanyl 5'-yl imidodiphosphate increased the rate of dissociation of [125I]galanin. In competition studies, guanyl 5'-yl imidodiphosphate decreased the IC50 s of unlabeled galanin which were homogenized around 4 nM in most telencephalic and hypothalamic regions. Thus, the guanyl 5'-yl imidodiphosphate-induced stimulation of [125I]galanin specific binding measured in the neuroendocrine and autonomic hypothalamus is linked to an increase in receptor capacity and not to a rise in receptor affinity. Both inhibitory and stimulatory guanyl 5'-yl imidodiphosphate effects observed in [125I]galanin equilibrium binding studies were dose-dependent and guanine nucleotide-specific with guanyl 5'-yl imidodiphosphate more potent than GTP or GDP.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279457", "title": "Chronic exposure to morphine does not induce dependence at the level of the calcium channel current in human SH-SY5Y cells.", "content": "mu-Opioid receptors mediate inhibition of the N-type calcium channel current in the human neuroblastoma cell line SH-SY5Y. We have previously shown that chronic exposure to morphine induces homologous tolerance to this effect. Here we show that chronic incubation with morphine (1 microM for three to seven days) does not, however, induce physical dependence at the level of the calcium channel current. Initial experiments were performed using the whole cell voltage-clamp technique. Chronically treated cells were bathed in superfusate which also contained morphine (1 microM). On washout of morphine the current amplitude increased by 12% and this was reversed by re-addition of morphine. Naloxone (1 microM) elicited a similar increase. However, this increase is most likely due to a reversal of the residual inhibitory effect of morphine on the calcium channel current rather than being a novel withdrawal response. Chronic exposure to morphine did not change the voltage-sensitivity of the calcium channel current or induce the appearance of a current sensitive to the L-type calcium channel agonists Bay K 8644 (3 microM) and S(+)-PN 202-791 (1 microM). In a further series of experiments the nystatin-perforated patch technique was employed in order to prevent washout of any L-type current in these cells. Under these conditions a Bay K 8644-sensitive, L-type current was unmasked following treatment with omega Conus Toxin GVIA. The peak current was depressed by omega Conus Toxin GVIA (1 microM) by approximately 90% both in control cells and cells chronically exposed to morphine. Now Bay K 8644 (3 microM) almost doubled the remaining current but the effect was equal in both groups of cells. It is concluded that chronic exposure to morphine does not induce physical dependence and a withdrawal syndrome in the human SH-SY5Y neuroblastoma cell line by changing either N-type or L-type calcium channel activity.", "contents": "Chronic exposure to morphine does not induce dependence at the level of the calcium channel current in human SH-SY5Y cells. mu-Opioid receptors mediate inhibition of the N-type calcium channel current in the human neuroblastoma cell line SH-SY5Y. We have previously shown that chronic exposure to morphine induces homologous tolerance to this effect. Here we show that chronic incubation with morphine (1 microM for three to seven days) does not, however, induce physical dependence at the level of the calcium channel current. Initial experiments were performed using the whole cell voltage-clamp technique. Chronically treated cells were bathed in superfusate which also contained morphine (1 microM). On washout of morphine the current amplitude increased by 12% and this was reversed by re-addition of morphine. Naloxone (1 microM) elicited a similar increase. However, this increase is most likely due to a reversal of the residual inhibitory effect of morphine on the calcium channel current rather than being a novel withdrawal response. Chronic exposure to morphine did not change the voltage-sensitivity of the calcium channel current or induce the appearance of a current sensitive to the L-type calcium channel agonists Bay K 8644 (3 microM) and S(+)-PN 202-791 (1 microM). In a further series of experiments the nystatin-perforated patch technique was employed in order to prevent washout of any L-type current in these cells. Under these conditions a Bay K 8644-sensitive, L-type current was unmasked following treatment with omega Conus Toxin GVIA. The peak current was depressed by omega Conus Toxin GVIA (1 microM) by approximately 90% both in control cells and cells chronically exposed to morphine. Now Bay K 8644 (3 microM) almost doubled the remaining current but the effect was equal in both groups of cells. It is concluded that chronic exposure to morphine does not induce physical dependence and a withdrawal syndrome in the human SH-SY5Y neuroblastoma cell line by changing either N-type or L-type calcium channel activity."} {"id": "PMID:1279458", "title": "Evidence that the masticatory muscles receive a direct innervation from cell group k in the rabbit.", "content": "These experiments have shown that a group of neurons lateral to the trigeminal motor nucleus innervates the muscles of mastication. The work began to describe the location of digastric last-order interneurons, using the technique of transneuronal labeling with wheatgerm agglutinin-conjugated horseradish peroxide injected into the left digastric muscle of rabbits under general anaesthesia. Four to eight days later, the animals were killed with an overdose of anaesthetic and perfused. Coronal sections of the frozen brainstem were cut at 20 microns thickness and processed for peroxidase activity. Motoneurons in the ventral and caudal divisions of the trigeminal motor nucleus were labeled in all animals as expected. An additional population of neurons located ventrolaterally to the motor nucleus in cell group k were also found to be labeled if the survival time was five days or more. In an attempt to determine whether cell group k neurons were labeled transynaptically, two series of control experiments were carried out. In the first, crystals of fluorescein- and rhodamine-conjugated dextran amines and horseradish peroxidase were applied directly to central ends of cut digastric nerves. In the second, central ends of cut digastric nerves were enclosed in cuffs containing 40-60% horseradish peroxidase solutions. Again, neurons in both the trigeminal motor nucleus and cell group k were labeled suggesting that neurons within cell group k project to the digastric muscle. Similar experiments using dextran amines and wheatgerm peroxidase were carried out on the masseter muscle. Motoneurons in the dorsomedial and rostral half of the trigeminal motor nucleus, as well as primary afferent cell bodies in the mesencephalic nucleus of the trigeminal nerve, were labeled in all experiments. In addition, a population of neurons in cell group k, dorsal to those associated with the digastric muscle, were found to contain each one of the reaction products. Since it is thought that only the wheatgerm agglutinin-conjugated horseradish peroxidase transferred from one neuron to another, we conclude that cell group k neurons provide an additional innervation to the digastric and masseter muscles.", "contents": "Evidence that the masticatory muscles receive a direct innervation from cell group k in the rabbit. These experiments have shown that a group of neurons lateral to the trigeminal motor nucleus innervates the muscles of mastication. The work began to describe the location of digastric last-order interneurons, using the technique of transneuronal labeling with wheatgerm agglutinin-conjugated horseradish peroxide injected into the left digastric muscle of rabbits under general anaesthesia. Four to eight days later, the animals were killed with an overdose of anaesthetic and perfused. Coronal sections of the frozen brainstem were cut at 20 microns thickness and processed for peroxidase activity. Motoneurons in the ventral and caudal divisions of the trigeminal motor nucleus were labeled in all animals as expected. An additional population of neurons located ventrolaterally to the motor nucleus in cell group k were also found to be labeled if the survival time was five days or more. In an attempt to determine whether cell group k neurons were labeled transynaptically, two series of control experiments were carried out. In the first, crystals of fluorescein- and rhodamine-conjugated dextran amines and horseradish peroxidase were applied directly to central ends of cut digastric nerves. In the second, central ends of cut digastric nerves were enclosed in cuffs containing 40-60% horseradish peroxidase solutions. Again, neurons in both the trigeminal motor nucleus and cell group k were labeled suggesting that neurons within cell group k project to the digastric muscle. Similar experiments using dextran amines and wheatgerm peroxidase were carried out on the masseter muscle. Motoneurons in the dorsomedial and rostral half of the trigeminal motor nucleus, as well as primary afferent cell bodies in the mesencephalic nucleus of the trigeminal nerve, were labeled in all experiments. In addition, a population of neurons in cell group k, dorsal to those associated with the digastric muscle, were found to contain each one of the reaction products. Since it is thought that only the wheatgerm agglutinin-conjugated horseradish peroxidase transferred from one neuron to another, we conclude that cell group k neurons provide an additional innervation to the digastric and masseter muscles."} {"id": "PMID:1279459", "title": "Light and electron microscopic localization of retrogradely transported neurotensin in rat nigrostriatal dopaminergic neurons.", "content": "We previously demonstrated the existence of a retrograde axonal transport of radioactivity to the substantia nigra pars compacta following injection of mono-iodinated neurotensin in rat neostriatum. In the present study, the topographical and cellular distribution of this retrogradely transported material was examined by light and electron microscopic autoradiography. Four and a half hours after unilateral injection of [125I]neurotensin in the caudoputamen, retrogradely labelled neuronal cell bodies were detected by light microscopic autoradiography throughout the ipsilateral substantia nigra pars compacta as well as within the ventral tegmental area and retrorubral field. In semithin sections, silver grains were prevalent over the perinuclear cytoplasm of neuronal cell bodies but were also detected over neuronal nuclei. Analysis of electron microscopic autoradiographs revealed that the vast majority (greater than 85%) were associated with neuronal perikarya, unmyelinated and myelinated axons, dendrites and terminals. Within the soma, a significant proportion of silver grains (16% of somatic grains) was detected over the nucleus. However, the majority were identified over the cytoplasm where they often encompassed cytoplasmic organelles, including rough endoplasmic reticulum, mitochondria, Golgi apparatus, lysosomes, and multi-vesicular bodies. In dendrites and axons, a substantial percentage of silver grains (63-89%) was localized over the plasma membrane. A minor proportion (13% of total) of the autoradiographic labelling was detected over myelin sheaths, astrocytes, and oligodendrocytes. The present results are consistent with previous light-microscopic evidence for internalization and retrograde transport of intrastriatal neurotensin within nigrostriatal dopaminergic neurons. They further suggest that retrogradely transported neurotensin may be processed along a variety of intracellular pathways including those mediating degradation in lysosomes and recycling in rough endoplasmic reticulum. The detection of specific autoradiographic labelling in the nucleus supports the concept that neurotensin alone, or complexed to its receptor, might be involved in the regulation of gene expression through direct or indirect interactions with nuclear DNA. Consequently, the retrograde transport of neurotensin in nigrostriatal dopaminergic neurons might provide a vehicle through which events occurring at the level of the axon terminal may initiate long-term biological responses.", "contents": "Light and electron microscopic localization of retrogradely transported neurotensin in rat nigrostriatal dopaminergic neurons. We previously demonstrated the existence of a retrograde axonal transport of radioactivity to the substantia nigra pars compacta following injection of mono-iodinated neurotensin in rat neostriatum. In the present study, the topographical and cellular distribution of this retrogradely transported material was examined by light and electron microscopic autoradiography. Four and a half hours after unilateral injection of [125I]neurotensin in the caudoputamen, retrogradely labelled neuronal cell bodies were detected by light microscopic autoradiography throughout the ipsilateral substantia nigra pars compacta as well as within the ventral tegmental area and retrorubral field. In semithin sections, silver grains were prevalent over the perinuclear cytoplasm of neuronal cell bodies but were also detected over neuronal nuclei. Analysis of electron microscopic autoradiographs revealed that the vast majority (greater than 85%) were associated with neuronal perikarya, unmyelinated and myelinated axons, dendrites and terminals. Within the soma, a significant proportion of silver grains (16% of somatic grains) was detected over the nucleus. However, the majority were identified over the cytoplasm where they often encompassed cytoplasmic organelles, including rough endoplasmic reticulum, mitochondria, Golgi apparatus, lysosomes, and multi-vesicular bodies. In dendrites and axons, a substantial percentage of silver grains (63-89%) was localized over the plasma membrane. A minor proportion (13% of total) of the autoradiographic labelling was detected over myelin sheaths, astrocytes, and oligodendrocytes. The present results are consistent with previous light-microscopic evidence for internalization and retrograde transport of intrastriatal neurotensin within nigrostriatal dopaminergic neurons. They further suggest that retrogradely transported neurotensin may be processed along a variety of intracellular pathways including those mediating degradation in lysosomes and recycling in rough endoplasmic reticulum. The detection of specific autoradiographic labelling in the nucleus supports the concept that neurotensin alone, or complexed to its receptor, might be involved in the regulation of gene expression through direct or indirect interactions with nuclear DNA. Consequently, the retrograde transport of neurotensin in nigrostriatal dopaminergic neurons might provide a vehicle through which events occurring at the level of the axon terminal may initiate long-term biological responses."} {"id": "PMID:1279460", "title": "Substance P opens cation channels and closes potassium channels in rat locus coeruleus neurons.", "content": "Whole-cell recordings were made from neurons of the rat locus coeruleus in a tissue slice removed from rat brain. Substance P caused an inward current in cells voltage-clamped at -60 mV. The effect of substance P was concentration-dependent (30 nM-3 microM) and was mimicked by similar concentrations of substance K and neuromedin K. The inward current resulted predominantly from an increase in membrane cation conductance; in potassium-free solutions it reversed polarity at about 12 mV. Substance P also reduced the conductance of an inwardly rectifying potassium current; this action was studied with low external sodium concentration. It is concluded that substance P excites rat locus coeruleus neurons by activating an intracellular transduction pathway leading to both cation conductance increase and potassium conductance decrease.", "contents": "Substance P opens cation channels and closes potassium channels in rat locus coeruleus neurons. Whole-cell recordings were made from neurons of the rat locus coeruleus in a tissue slice removed from rat brain. Substance P caused an inward current in cells voltage-clamped at -60 mV. The effect of substance P was concentration-dependent (30 nM-3 microM) and was mimicked by similar concentrations of substance K and neuromedin K. The inward current resulted predominantly from an increase in membrane cation conductance; in potassium-free solutions it reversed polarity at about 12 mV. Substance P also reduced the conductance of an inwardly rectifying potassium current; this action was studied with low external sodium concentration. It is concluded that substance P excites rat locus coeruleus neurons by activating an intracellular transduction pathway leading to both cation conductance increase and potassium conductance decrease."} {"id": "PMID:1279461", "title": "Topography and functional role of dopaminergic projections from the ventral mesencephalic tegmentum to the ventral pallidum.", "content": "A dopaminergic projection from the ventral tegmental area to the ventral pallidum was identified in the rat using anterograde tract tracing and combined retrograde tracing-immunocytochemistry. The projection was found to be topographically organized such that fibers innervating the ventromedial ventral pallidum arose from neurons located along the midline nuclei of the ventral mesencephalon, including the nucleus interfascicularis and nucleus linearis caudalis. Ventral tegmental neurons situated more laterally, in the nucleus parabrachialis pigmentosus and nucleus paranigralis, projected to the ventromedial and dorsolateral ventral pallidum. The substantia nigra did not supply a major contribution to this projection. The proportion of ventral tegmental area dopaminergic neurons projecting to the ventral pallidum ranged from approximately 30% to 60%. The functional significance of the projection is indicated since intra-ventral pallidum microinjections of dopamine elicited a dose-dependent increase in locomotor activity. Furthermore, whereas pretreatment of the ventral pallidum with the GABAA agonist muscimol has been shown to attenuate opioid-induced locomotor activity elicited from the ventral pallidum, it did not attenuate the dopamine-induced motor response. Thus, while mu-opioids in the ventral pallidum may presynaptically regulate GABAergic efferents from the nucleus accumbens, it appears that the dopaminergic input directly influences the ventral pallidal output neuron which is involved in locomotion.", "contents": "Topography and functional role of dopaminergic projections from the ventral mesencephalic tegmentum to the ventral pallidum. A dopaminergic projection from the ventral tegmental area to the ventral pallidum was identified in the rat using anterograde tract tracing and combined retrograde tracing-immunocytochemistry. The projection was found to be topographically organized such that fibers innervating the ventromedial ventral pallidum arose from neurons located along the midline nuclei of the ventral mesencephalon, including the nucleus interfascicularis and nucleus linearis caudalis. Ventral tegmental neurons situated more laterally, in the nucleus parabrachialis pigmentosus and nucleus paranigralis, projected to the ventromedial and dorsolateral ventral pallidum. The substantia nigra did not supply a major contribution to this projection. The proportion of ventral tegmental area dopaminergic neurons projecting to the ventral pallidum ranged from approximately 30% to 60%. The functional significance of the projection is indicated since intra-ventral pallidum microinjections of dopamine elicited a dose-dependent increase in locomotor activity. Furthermore, whereas pretreatment of the ventral pallidum with the GABAA agonist muscimol has been shown to attenuate opioid-induced locomotor activity elicited from the ventral pallidum, it did not attenuate the dopamine-induced motor response. Thus, while mu-opioids in the ventral pallidum may presynaptically regulate GABAergic efferents from the nucleus accumbens, it appears that the dopaminergic input directly influences the ventral pallidal output neuron which is involved in locomotion."} {"id": "PMID:1279462", "title": "Afferent connections of the parvocellular reticular formation: a horseradish peroxidase study in the rat.", "content": "The afferent connections of the parvocellular reticular formation were systematically investigated in the rat with the aid of retrograde and anterograde horseradish peroxidase tracer techniques. The results indicate that the parvocellular reticular formation receives its main input from several territories of the cerebral cortex (namely the first motor, primary somatosensory and granular insular areas), districts of the reticular formation (including its contralateral counterpart, the intermediate reticular nucleus, the nucleus of Probst's bundle, the dorsal paragigantocellular nucleus, the alpha part of the gigantocellular reticular nucleus, the dorsal and ventral reticular nuclei of the medulla, and the mesencephalic reticular formation), the supratrigeminal nucleus and the deep cerebellar nuclei. Moderate to substantial input to the parvocellular reticular formation appears to come from the central amygdaloid nucleus, the parvocellular division of the red nucleus, and the orofacial and gustatory sensory cell groups (comprising the mesencephalic, principal and spinal trigeminal nuclei, and the rostral part of the nucleus of the solitary tract), whereas many other structures, including the substantia innominata, the field H2 of Forel, hypothalamic nuclei, the superior colliculus, the substantia nigra pars reticulata, the retrorubral field and the parabrachial complex, seem to represent relatively modest additional input sources. Some of these projections appear to be topographically distributed within the parvocellular reticular formation. From the present results it appears that the parvocellular reticular formation receives afferents from a restricted group of sensory structures. This finding calls into question the traditional characterization of the parvocellular reticular formation as an intermediate link between the sensory nuclei of the cranial nerves and the medial magnocellular reticular districts, identified as the effector components of the reticular apparatus. Some of the possible physiological correlates of the fiber connections of the parvocellular reticular formation in the context of oral motor behaviors, autonomic regulations, respiratory phenomena and sleep-waking mechanisms are briefly discussed.", "contents": "Afferent connections of the parvocellular reticular formation: a horseradish peroxidase study in the rat. The afferent connections of the parvocellular reticular formation were systematically investigated in the rat with the aid of retrograde and anterograde horseradish peroxidase tracer techniques. The results indicate that the parvocellular reticular formation receives its main input from several territories of the cerebral cortex (namely the first motor, primary somatosensory and granular insular areas), districts of the reticular formation (including its contralateral counterpart, the intermediate reticular nucleus, the nucleus of Probst's bundle, the dorsal paragigantocellular nucleus, the alpha part of the gigantocellular reticular nucleus, the dorsal and ventral reticular nuclei of the medulla, and the mesencephalic reticular formation), the supratrigeminal nucleus and the deep cerebellar nuclei. Moderate to substantial input to the parvocellular reticular formation appears to come from the central amygdaloid nucleus, the parvocellular division of the red nucleus, and the orofacial and gustatory sensory cell groups (comprising the mesencephalic, principal and spinal trigeminal nuclei, and the rostral part of the nucleus of the solitary tract), whereas many other structures, including the substantia innominata, the field H2 of Forel, hypothalamic nuclei, the superior colliculus, the substantia nigra pars reticulata, the retrorubral field and the parabrachial complex, seem to represent relatively modest additional input sources. Some of these projections appear to be topographically distributed within the parvocellular reticular formation. From the present results it appears that the parvocellular reticular formation receives afferents from a restricted group of sensory structures. This finding calls into question the traditional characterization of the parvocellular reticular formation as an intermediate link between the sensory nuclei of the cranial nerves and the medial magnocellular reticular districts, identified as the effector components of the reticular apparatus. Some of the possible physiological correlates of the fiber connections of the parvocellular reticular formation in the context of oral motor behaviors, autonomic regulations, respiratory phenomena and sleep-waking mechanisms are briefly discussed."} {"id": "PMID:1279463", "title": "Synaptic organization of GABAergic inputs from the striatum and the globus pallidus onto neurons in the substantia nigra and retrorubral field which project to the medullary reticular formation.", "content": "Anatomical tract-tracing and immunohistochemical techniques involving correlated light and electron microscopy were used to determine whether the descending striatal and pallidal afferents to the substantia nigra pars reticulata converge onto individual neurons projecting to the pontomedullary and medullary reticular formation in the rat. Injections of biocytin into the ventrolateral region of the striatum and Phaseolus vulgaris-leucoagglutinin into the ventrolateral and caudal regions of the globus pallidus led to overlapping anterogradely labelled terminal fields within the dorsolateral substantia nigra pars reticulata. These terminal fields were punctuated by neurons which had been retrogradely labelled following injections of wheatgerm agglutinin conjugated to horseradish peroxidase into the lateral pontomedullary reticular formation. The anterogradely labelled striatal and pallidal terminals displayed different morphological characteristics; the striatal terminals were small and diffusely distributed throughout the neuropil without any particular neuronal association whereas the pallidal terminals were large and formed pericellular baskets around the perikarya of retrogradely and non-retrogradely labelled nigral neurons. In areas of the substantia nigra where there was an overlap between the two terminal fields, individual retrogradely labelled nigroreticular neurons were found to be apposed by both sets of anterogradely labelled terminals. Electron microscopic analysis revealed that the striatonigral and pallidonigral terminals displayed different ultrastructural features, the striatal terminals were small, contained few mitochondria and formed symmetric synaptic contacts predominantly with the distal dendrites of nigroreticular neurons whereas the pallidal terminals were large, contained numerous mitochondria and formed symmetric synaptic contacts preferentially with perikarya and proximal dendrites of nigroreticular neurons. Post-embedding immunohistochemical staining revealed that both striatonigral and pallidonigral terminals, some which formed synaptic contact with nigroreticular neurons, displayed GABA immunoreactivity. Examination of twelve retrogradely labelled neurons in the electron microscope revealed that all received synaptic inputs from both sets of anterogradely labelled terminals. In addition to the substantia nigra pars reticulata, neurons of the retrorubral field were also retrogradely labelled following injections of wheatgerm agglutinin conjugated to horseradish peroxidase into pontomedullary reticular formation. These retrorubroreticular neurons were part of a continuum of labelled cells which extended from the dorsolateral substantia nigra pars reticulata caudally into the retrorubral field. When combined with anterograde tracing methods it was found that the retrorubroreticular neurons received synaptic inputs from pallidal terminals which were morphologically similar to the pallidonigral terminals and formed symmetric synapses with the neuronal somata and proximal dendrites. In contrast to nigroreticular neurons, the stratonigral terminals were not seen in contact with retrorubroreticular cells.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Synaptic organization of GABAergic inputs from the striatum and the globus pallidus onto neurons in the substantia nigra and retrorubral field which project to the medullary reticular formation. Anatomical tract-tracing and immunohistochemical techniques involving correlated light and electron microscopy were used to determine whether the descending striatal and pallidal afferents to the substantia nigra pars reticulata converge onto individual neurons projecting to the pontomedullary and medullary reticular formation in the rat. Injections of biocytin into the ventrolateral region of the striatum and Phaseolus vulgaris-leucoagglutinin into the ventrolateral and caudal regions of the globus pallidus led to overlapping anterogradely labelled terminal fields within the dorsolateral substantia nigra pars reticulata. These terminal fields were punctuated by neurons which had been retrogradely labelled following injections of wheatgerm agglutinin conjugated to horseradish peroxidase into the lateral pontomedullary reticular formation. The anterogradely labelled striatal and pallidal terminals displayed different morphological characteristics; the striatal terminals were small and diffusely distributed throughout the neuropil without any particular neuronal association whereas the pallidal terminals were large and formed pericellular baskets around the perikarya of retrogradely and non-retrogradely labelled nigral neurons. In areas of the substantia nigra where there was an overlap between the two terminal fields, individual retrogradely labelled nigroreticular neurons were found to be apposed by both sets of anterogradely labelled terminals. Electron microscopic analysis revealed that the striatonigral and pallidonigral terminals displayed different ultrastructural features, the striatal terminals were small, contained few mitochondria and formed symmetric synaptic contacts predominantly with the distal dendrites of nigroreticular neurons whereas the pallidal terminals were large, contained numerous mitochondria and formed symmetric synaptic contacts preferentially with perikarya and proximal dendrites of nigroreticular neurons. Post-embedding immunohistochemical staining revealed that both striatonigral and pallidonigral terminals, some which formed synaptic contact with nigroreticular neurons, displayed GABA immunoreactivity. Examination of twelve retrogradely labelled neurons in the electron microscope revealed that all received synaptic inputs from both sets of anterogradely labelled terminals. In addition to the substantia nigra pars reticulata, neurons of the retrorubral field were also retrogradely labelled following injections of wheatgerm agglutinin conjugated to horseradish peroxidase into pontomedullary reticular formation. These retrorubroreticular neurons were part of a continuum of labelled cells which extended from the dorsolateral substantia nigra pars reticulata caudally into the retrorubral field. When combined with anterograde tracing methods it was found that the retrorubroreticular neurons received synaptic inputs from pallidal terminals which were morphologically similar to the pallidonigral terminals and formed symmetric synapses with the neuronal somata and proximal dendrites. In contrast to nigroreticular neurons, the stratonigral terminals were not seen in contact with retrorubroreticular cells.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279464", "title": "Topographical organization of the nigrotectal projection in rat: evidence for segregated channels.", "content": "Recent evidence suggests that projections from the superior colliculus to the brainstem in rat are organized into a series of anatomically segregated output channels. To understand how collicular function may be modified by the basal ganglia it is important to know whether particular output modules of the superior colliculus can be selectively influenced by input from substantia nigra. The purpose of the present study was, therefore, to examine in more detail topography within the nigrotectal system in the rat. Small injections (10-50 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish peroxidase were made at different locations within substantia nigra and surrounding structures. A discontinuous puff-like pattern of anterogradely transported label was found in medial and caudal parts of the ipsilateral intermediate layers of the superior colliculus. In contrast, the rostrolateral enlargement of the intermediate layers contained a greater density of more evenly distributed terminal label. Injection sites associated with this dense pattern of laterally located label were concentrated in lateral pars reticulata, while the puff-like pattern was produced by injections into ventromedial pars reticulata. Retrograde tracing experiments with the fluorescent dyes True Blue and Fast Blue revealed that injections involving the rostrolateral intermediate layers were consistently associated with a restricted column of labelled cells in the dorsolateral part of ipsilateral pars reticulata. Comparable injections into medial and caudal regions of the superior colliculus produced retrograde labelling in ventral and medial parts of the rostral two-thirds of pars reticulata. Both anterograde and retrograde tracing data indicated that contralateral nigrotectal projections arise from cells located in ventral and medial pars reticulata. The present results suggest that the main ipsilateral projection from substantia nigra pars reticulata to the superior colliculus comprises two main components characterized by regionally segregated populations of output cells and spatially separated zones of termination. Of particular interest is the apparent close alignment between terminal zones of the nigrotectal channels and previously defined populations of crossed descending output cells in the superior colliculus. Thus, the rostrolateral intermediate layers contain a concentration of terminals specifically from dorsolateral pars reticulata and output cells which project to the contralateral caudal medulla and spinal cord. Conversely, the medial and caudal intermediate layers receive terminals from ventral and medial pars reticulata and contain cells which project specifically to contralateral regions of the paramedian pontine and medullary reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Topographical organization of the nigrotectal projection in rat: evidence for segregated channels. Recent evidence suggests that projections from the superior colliculus to the brainstem in rat are organized into a series of anatomically segregated output channels. To understand how collicular function may be modified by the basal ganglia it is important to know whether particular output modules of the superior colliculus can be selectively influenced by input from substantia nigra. The purpose of the present study was, therefore, to examine in more detail topography within the nigrotectal system in the rat. Small injections (10-50 nl) of a 1% solution of wheatgerm agglutinin conjugated with horseradish peroxidase were made at different locations within substantia nigra and surrounding structures. A discontinuous puff-like pattern of anterogradely transported label was found in medial and caudal parts of the ipsilateral intermediate layers of the superior colliculus. In contrast, the rostrolateral enlargement of the intermediate layers contained a greater density of more evenly distributed terminal label. Injection sites associated with this dense pattern of laterally located label were concentrated in lateral pars reticulata, while the puff-like pattern was produced by injections into ventromedial pars reticulata. Retrograde tracing experiments with the fluorescent dyes True Blue and Fast Blue revealed that injections involving the rostrolateral intermediate layers were consistently associated with a restricted column of labelled cells in the dorsolateral part of ipsilateral pars reticulata. Comparable injections into medial and caudal regions of the superior colliculus produced retrograde labelling in ventral and medial parts of the rostral two-thirds of pars reticulata. Both anterograde and retrograde tracing data indicated that contralateral nigrotectal projections arise from cells located in ventral and medial pars reticulata. The present results suggest that the main ipsilateral projection from substantia nigra pars reticulata to the superior colliculus comprises two main components characterized by regionally segregated populations of output cells and spatially separated zones of termination. Of particular interest is the apparent close alignment between terminal zones of the nigrotectal channels and previously defined populations of crossed descending output cells in the superior colliculus. Thus, the rostrolateral intermediate layers contain a concentration of terminals specifically from dorsolateral pars reticulata and output cells which project to the contralateral caudal medulla and spinal cord. Conversely, the medial and caudal intermediate layers receive terminals from ventral and medial pars reticulata and contain cells which project specifically to contralateral regions of the paramedian pontine and medullary reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279465", "title": "Peripheral injury and anterograde transport of wheat germ agglutinin-horse radish peroxidase to the spinal cord.", "content": "Previous observations have revealed labeling in the extracellular space surrounding boutons and unmyelinated fibers in superficial laminae of the spinal cord after injection of the tracer wheat germ agglutinin conjugated to horseradish peroxidase in dorsal root ganglia. The degree of extracellular labeling appeared related to the extent of the damage to the ganglia at the time of the injection. To determine whether injury might produce extracellular labeling, we investigated the effects of unilateral nerve crush or transection on spinal labeling after bilateral injections of the tracer into sciatic nerves. Confirming previous reports, labeling was confined to small dorsal root ganglion cells and to spinal laminae I and II, suggesting a selective affinity of this tracer for unmyelinated fibers. Labeling of both ganglion neurons and superficial spinal laminae was increased on the injured side, probably as a result of increased efficiency of receptor-mediated endocytosis. Electron microscopical observations revealed that the tracer was largely confined to unmyelinated dorsal root fibers bilaterally; a higher percentage of these fibers were labeled on the injured side. In the dorsal horn, the tracer was predominantly within unmyelinated axons and their terminals on the control side, whereas most of the labeling was extracellular and transneuronal on the injured side. The extracellular labeling surrounded unmyelinated fibers and their terminals in the spinal cord, but was excluded from the synaptic cleft. The demonstration that injury is accompanied by significantly increased release of this tracer from the terminals of unmyelinated fibers into the extracellular space suggests that endogenous substances may be released after peripheral lesions as a central signal of injury.", "contents": "Peripheral injury and anterograde transport of wheat germ agglutinin-horse radish peroxidase to the spinal cord. Previous observations have revealed labeling in the extracellular space surrounding boutons and unmyelinated fibers in superficial laminae of the spinal cord after injection of the tracer wheat germ agglutinin conjugated to horseradish peroxidase in dorsal root ganglia. The degree of extracellular labeling appeared related to the extent of the damage to the ganglia at the time of the injection. To determine whether injury might produce extracellular labeling, we investigated the effects of unilateral nerve crush or transection on spinal labeling after bilateral injections of the tracer into sciatic nerves. Confirming previous reports, labeling was confined to small dorsal root ganglion cells and to spinal laminae I and II, suggesting a selective affinity of this tracer for unmyelinated fibers. Labeling of both ganglion neurons and superficial spinal laminae was increased on the injured side, probably as a result of increased efficiency of receptor-mediated endocytosis. Electron microscopical observations revealed that the tracer was largely confined to unmyelinated dorsal root fibers bilaterally; a higher percentage of these fibers were labeled on the injured side. In the dorsal horn, the tracer was predominantly within unmyelinated axons and their terminals on the control side, whereas most of the labeling was extracellular and transneuronal on the injured side. The extracellular labeling surrounded unmyelinated fibers and their terminals in the spinal cord, but was excluded from the synaptic cleft. The demonstration that injury is accompanied by significantly increased release of this tracer from the terminals of unmyelinated fibers into the extracellular space suggests that endogenous substances may be released after peripheral lesions as a central signal of injury."} {"id": "PMID:1279466", "title": "Sensory neuropeptide interactions in the production of plasma extravasation in the rat.", "content": "We used an experimental model of neurogenic inflammation to study the contribution of the primary afferent peptides substance P, calcitonin gene-related peptide, galanin and somatostatin to plasma extravasation in rat synovium. Perfusion of the C-fiber excitotoxin, capsaicin (1.6 mM), through the knee joint of the pentobarbital anesthetized rat, increased plasma extravasation transiently (< 30 min). Perfusion of substance P (1 microM) or calcitonin gene-related peptide (100 nM), two primary afferent neuropeptides that are released by acute capsaicin administration, had no significant effect on plasma extravasation. Co-perfusion of these two neuropeptides, however, evoked an increase in plasma extravasation that was greater than that produced by capsaicin remaining above 250% of the baseline level by the end of the perfusion period (55 min). Capsaicin co-perfused with either galanin (100 nM) or somatostatin (1 microM) failed to increase plasma extravasation. Neither galanin nor somatostatin significantly affected increase in plasma extravasation induced by co-perfusion of substance P plus calcitonin gene-related peptide. Therefore, we suggest that galanin and somatostatin inhibit, presynaptically, the release of substance P and calcitonin gene-related peptide from primary afferent terminals. The interactions among these four neuropeptides provide a novel mechanism for the regulation of primary afferent neurogenic inflammation.", "contents": "Sensory neuropeptide interactions in the production of plasma extravasation in the rat. We used an experimental model of neurogenic inflammation to study the contribution of the primary afferent peptides substance P, calcitonin gene-related peptide, galanin and somatostatin to plasma extravasation in rat synovium. Perfusion of the C-fiber excitotoxin, capsaicin (1.6 mM), through the knee joint of the pentobarbital anesthetized rat, increased plasma extravasation transiently (< 30 min). Perfusion of substance P (1 microM) or calcitonin gene-related peptide (100 nM), two primary afferent neuropeptides that are released by acute capsaicin administration, had no significant effect on plasma extravasation. Co-perfusion of these two neuropeptides, however, evoked an increase in plasma extravasation that was greater than that produced by capsaicin remaining above 250% of the baseline level by the end of the perfusion period (55 min). Capsaicin co-perfused with either galanin (100 nM) or somatostatin (1 microM) failed to increase plasma extravasation. Neither galanin nor somatostatin significantly affected increase in plasma extravasation induced by co-perfusion of substance P plus calcitonin gene-related peptide. Therefore, we suggest that galanin and somatostatin inhibit, presynaptically, the release of substance P and calcitonin gene-related peptide from primary afferent terminals. The interactions among these four neuropeptides provide a novel mechanism for the regulation of primary afferent neurogenic inflammation."} {"id": "PMID:1279468", "title": "[Postoperative hyperamylasemia: the evaluation of the efficacy of ranitidine in prevention].", "content": "The paper examines the role of ranitidine in the prevention of postoperative hyperamylasemia, a complication following major biliary tract surgery, especially if associated with intraoperative cholangiography. Forty patients underwent cholecystectomy and intraoperative cholangiography: calculosis of the choledochus was observed in 11 patients and a revision of the VBP was therefore carried out involving the transcystic insertion of Kehr's tube. Patients were randomly subdivided into two groups: group A (treated with 50 mg ranitidine 4 times a day e.v.) and group B (no anti H2 treatment). No significant differences were noted between the two groups with regard to the onset of hyperamylasemia, although it is worth reporting that ranitidine virtually eliminated all hemorrhagic complications due to ulcer or postoperative gastritis.", "contents": "[Postoperative hyperamylasemia: the evaluation of the efficacy of ranitidine in prevention]. The paper examines the role of ranitidine in the prevention of postoperative hyperamylasemia, a complication following major biliary tract surgery, especially if associated with intraoperative cholangiography. Forty patients underwent cholecystectomy and intraoperative cholangiography: calculosis of the choledochus was observed in 11 patients and a revision of the VBP was therefore carried out involving the transcystic insertion of Kehr's tube. Patients were randomly subdivided into two groups: group A (treated with 50 mg ranitidine 4 times a day e.v.) and group B (no anti H2 treatment). No significant differences were noted between the two groups with regard to the onset of hyperamylasemia, although it is worth reporting that ranitidine virtually eliminated all hemorrhagic complications due to ulcer or postoperative gastritis."} {"id": "PMID:1279469", "title": "[Duodenal adenocarcinoma. A case report].", "content": "The duodenal carcinoma is a rare malignant neoplasm (1-6% of all the tumors of the digestive tract). In this paper the authors review the clinical and diagnostic approach to the disease and discuss both the palliative and curative surgical therapy.", "contents": "[Duodenal adenocarcinoma. A case report]. The duodenal carcinoma is a rare malignant neoplasm (1-6% of all the tumors of the digestive tract). In this paper the authors review the clinical and diagnostic approach to the disease and discuss both the palliative and curative surgical therapy."} {"id": "PMID:1279470", "title": "Dystrophin-like immunoreactivity in monkey and human brain areas involved in learning and motor functions.", "content": "Two antidystrophin antibodies against different fragments of dystrophin were used to detect this polypeptide in monkey and human brains. Dystrophin was revealed by immunoperoxidase amplified with the biotin/avidin system and by immunoblotting. A dystrophin-like immunoreactivity was uniformly expressed in several brain regions implicated in learning and motor functions. Dystrophin function is not clear but our results raise the possibility that this protein may be involved in the cognitive impairment observed in several Duchenne muscular dystrophy (DMD) patients.", "contents": "Dystrophin-like immunoreactivity in monkey and human brain areas involved in learning and motor functions. Two antidystrophin antibodies against different fragments of dystrophin were used to detect this polypeptide in monkey and human brains. Dystrophin was revealed by immunoperoxidase amplified with the biotin/avidin system and by immunoblotting. A dystrophin-like immunoreactivity was uniformly expressed in several brain regions implicated in learning and motor functions. Dystrophin function is not clear but our results raise the possibility that this protein may be involved in the cognitive impairment observed in several Duchenne muscular dystrophy (DMD) patients."} {"id": "PMID:1279471", "title": "Quaking phenotype influences brain lipid-related mRNA levels.", "content": "Although lipids compose almost 80% of myelin, the influence of quaking on mRNAs encoding lipid biosynthetic enzymes and transport proteins has not been previously reported. Understanding the influence of quaking on myelin-specific and lipid-related mRNAs will be useful in determining the mechanism of the quaking defect. Stearoyl CoA desaturase (SCD) catalyzes a key step in the biosynthesis of oleic acid (C18:1, n-9), a major fatty acid in myelin. SCD, LDL receptor (LDLR) and apolipoprotein E (Apo E) mRNA levels are all reduced in neonatal quaking brains. In contrast to brain, quaking hepatic LDLR and Apo E mRNA levels are normal. These results indicate that lipid-related mRNAs are reduced in neonatal quaking brain, but the quaking liver is unaffected. The quaking defect influences gene expression in multiple cell types of glial lineage in the developing CNS.", "contents": "Quaking phenotype influences brain lipid-related mRNA levels. Although lipids compose almost 80% of myelin, the influence of quaking on mRNAs encoding lipid biosynthetic enzymes and transport proteins has not been previously reported. Understanding the influence of quaking on myelin-specific and lipid-related mRNAs will be useful in determining the mechanism of the quaking defect. Stearoyl CoA desaturase (SCD) catalyzes a key step in the biosynthesis of oleic acid (C18:1, n-9), a major fatty acid in myelin. SCD, LDL receptor (LDLR) and apolipoprotein E (Apo E) mRNA levels are all reduced in neonatal quaking brains. In contrast to brain, quaking hepatic LDLR and Apo E mRNA levels are normal. These results indicate that lipid-related mRNAs are reduced in neonatal quaking brain, but the quaking liver is unaffected. The quaking defect influences gene expression in multiple cell types of glial lineage in the developing CNS."} {"id": "PMID:1279472", "title": "Single-channel currents of NMDA type activated by L- and D-homocysteic acid in cerebellar granule cells in culture.", "content": "The whole-cell and the outside-out configurations of the patch-clamp technique were used to study macroscopic and single-channel currents evoked by the enantiomers of homocysteic acid, the sulphur containing analogue of glutamate, in cerebellar granule cells in culture. L-Homocysteic acid (L-HC, 15 microM) and D-homocysteic acid (D-HC, 50 microM) induced whole-cell currents of comparable amplitude, that were abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (AP-5) (20 microM). AMPA (100 microM) induced whole-cell currents which were not modified by AP-5 (20 microM) but were blocked by CNQX. In the outside-out configuration, both L-HC and D-HC (15 microM) elicited single-channel currents of the same conductance, mean open time and reversal potential as the NMDA-induced single-channel events. In the presence of Mg2+ (2 mM), D- and L-HC-induced single-channel currents were voltage-dependent. These data suggest that in cerebellar granule cells in culture, both L-HC and D-HC activate the same NMDA receptor channel complex.", "contents": "Single-channel currents of NMDA type activated by L- and D-homocysteic acid in cerebellar granule cells in culture. The whole-cell and the outside-out configurations of the patch-clamp technique were used to study macroscopic and single-channel currents evoked by the enantiomers of homocysteic acid, the sulphur containing analogue of glutamate, in cerebellar granule cells in culture. L-Homocysteic acid (L-HC, 15 microM) and D-homocysteic acid (D-HC, 50 microM) induced whole-cell currents of comparable amplitude, that were abolished by the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonovalerate (AP-5) (20 microM). AMPA (100 microM) induced whole-cell currents which were not modified by AP-5 (20 microM) but were blocked by CNQX. In the outside-out configuration, both L-HC and D-HC (15 microM) elicited single-channel currents of the same conductance, mean open time and reversal potential as the NMDA-induced single-channel events. In the presence of Mg2+ (2 mM), D- and L-HC-induced single-channel currents were voltage-dependent. These data suggest that in cerebellar granule cells in culture, both L-HC and D-HC activate the same NMDA receptor channel complex."} {"id": "PMID:1279473", "title": "The substance P (NK1) receptor antagonist (+/-)-CP-96,345 causes sedation and motor impairment in Swiss albino mice in the black-and-white box behavioral paradigm.", "content": "In order to test the suggested involvement of substance P (NK1) receptors in anxiety, the non-peptide NK1 antagonist (+/-)-CP-96,345 was tested in Swiss albino mice using the black-and-white box behavioral paradigm. Intraperitoneal (+/-)-CP-96,345 dose-dependently decreased the motor activity and the number of exploratory rearings in both the brightly lit and dark compartment as well as the transitions between the compartments, whereas it increased the latency of the initial movement into the dark compartment as well as the time spent in the light section. ED50 or ID50 values ranged from 1.9 to 3.6 mg/kg and Hill slopes from 1.4 to 5.0. (+/-)-CP-96,345 also produced rotatory behavior of no preferred lateralization as well as the Straub phenomenon in some animals. The effects of (+/-)-CP-96,345 (5 mg/kg) were not affected by 2 mg/kg naloxone (i.p.) which was also ineffective when given alone. Thus, (+/-)-CP-96,345 does not display any anxiogenic effect but causes dose-dependent sedation and motor impairment.", "contents": "The substance P (NK1) receptor antagonist (+/-)-CP-96,345 causes sedation and motor impairment in Swiss albino mice in the black-and-white box behavioral paradigm. In order to test the suggested involvement of substance P (NK1) receptors in anxiety, the non-peptide NK1 antagonist (+/-)-CP-96,345 was tested in Swiss albino mice using the black-and-white box behavioral paradigm. Intraperitoneal (+/-)-CP-96,345 dose-dependently decreased the motor activity and the number of exploratory rearings in both the brightly lit and dark compartment as well as the transitions between the compartments, whereas it increased the latency of the initial movement into the dark compartment as well as the time spent in the light section. ED50 or ID50 values ranged from 1.9 to 3.6 mg/kg and Hill slopes from 1.4 to 5.0. (+/-)-CP-96,345 also produced rotatory behavior of no preferred lateralization as well as the Straub phenomenon in some animals. The effects of (+/-)-CP-96,345 (5 mg/kg) were not affected by 2 mg/kg naloxone (i.p.) which was also ineffective when given alone. Thus, (+/-)-CP-96,345 does not display any anxiogenic effect but causes dose-dependent sedation and motor impairment."} {"id": "PMID:1279474", "title": "Capsaicin prevents the adrenocorticotropin-induced improvement of cardiovascular function and survival in hemorrhage-shocked rats.", "content": "A volume-controlled hemorrhagic shock was produced in anesthetized rats by intermittent bleeding from an iliac vein over a period of 20-30 min, until the carotid mean arterial pressure (MAP) stabilized around 20-24 mmHg. In this condition, which caused the death of all saline-treated animals within 25-30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropin fragment 1-24 (ACTH(1-24)) at a dose of 160 micrograms/kg promptly restored MAP, as well as pulse pressure, heart rate and respiratory function, and greatly prolonged the survival time. Capsaicin (125 mg/kg cumulatively, s.c., 1 week before) completely prevented the anti-shock effect of ACTH(1-24), which, on the other hand, was shared by i.v. [Nle11]-substance P (SP) (200-300 micrograms/kg). Finally the SP-antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP prevented the effect of ACTH(1-24). These results suggest that SP-containing nerve fibers are required for the effect of ACTH in hemorrhagic shock.", "contents": "Capsaicin prevents the adrenocorticotropin-induced improvement of cardiovascular function and survival in hemorrhage-shocked rats. A volume-controlled hemorrhagic shock was produced in anesthetized rats by intermittent bleeding from an iliac vein over a period of 20-30 min, until the carotid mean arterial pressure (MAP) stabilized around 20-24 mmHg. In this condition, which caused the death of all saline-treated animals within 25-30 min, the intravenous (i.v.) bolus injection of the adrenocorticotropin fragment 1-24 (ACTH(1-24)) at a dose of 160 micrograms/kg promptly restored MAP, as well as pulse pressure, heart rate and respiratory function, and greatly prolonged the survival time. Capsaicin (125 mg/kg cumulatively, s.c., 1 week before) completely prevented the anti-shock effect of ACTH(1-24), which, on the other hand, was shared by i.v. [Nle11]-substance P (SP) (200-300 micrograms/kg). Finally the SP-antagonist [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP prevented the effect of ACTH(1-24). These results suggest that SP-containing nerve fibers are required for the effect of ACTH in hemorrhagic shock."} {"id": "PMID:1279475", "title": "Release of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity from rat isolated soleus muscle by low pH, capsaicin and potassium.", "content": "Capsaicin (10 microM), KCl (80 mM) or superfusion with a low pH medium (pH 5 or 6) produced a significant increase of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) outflow from the superfused rat isolated soleus muscle. CGRP-LI outflow produced by capsaicin or pH 5 medium was totally abolished in a calcium free medium containing EDTA (1 mM) and the effect of pH 5 medium was prevented by a previous application of capsaicin. Ruthenium red (10 microM) produced a marked inhibition of CGRP-LI release produced by capsaicin or pH 5 medium (69 and 84%, resp.), without affecting that evoked by KCl. These findings demonstrate that protons activate capsaicin-sensitive primary afferents in rat skeletal muscle through a Ruthenium red-sensitive mechanism. Proton-induced CGRP-LI release in skeletal muscle could be of relevance during exercise and/or skeletal muscle ischemia.", "contents": "Release of calcitonin gene-related peptide-like (CGRP-LI) immunoreactivity from rat isolated soleus muscle by low pH, capsaicin and potassium. Capsaicin (10 microM), KCl (80 mM) or superfusion with a low pH medium (pH 5 or 6) produced a significant increase of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) outflow from the superfused rat isolated soleus muscle. CGRP-LI outflow produced by capsaicin or pH 5 medium was totally abolished in a calcium free medium containing EDTA (1 mM) and the effect of pH 5 medium was prevented by a previous application of capsaicin. Ruthenium red (10 microM) produced a marked inhibition of CGRP-LI release produced by capsaicin or pH 5 medium (69 and 84%, resp.), without affecting that evoked by KCl. These findings demonstrate that protons activate capsaicin-sensitive primary afferents in rat skeletal muscle through a Ruthenium red-sensitive mechanism. Proton-induced CGRP-LI release in skeletal muscle could be of relevance during exercise and/or skeletal muscle ischemia."} {"id": "PMID:1279476", "title": "Decreased cerebrospinal fluid neuropeptide-converting enzyme activity in monoarthritic rats.", "content": "The activity in rat cerebrospinal fluid (CSF) of dynorphin-converting enzyme (DCE) and substance P endopeptidase (SPE) was determined in control animals and in rats with monoarthritis. Enzymatic activities were measured with specific radioimmunoassays toward the N-terminal products Leu-enkephalin-Arg6 and substance P1-7, respectively. A monoarthritis stable during weeks 2-6 post-injection was induced by injection (0.05 ml) into one joint with Freund's adjuvant. Both SPE and DCE were significantly decreased 15 days after the intraarticular injection. Despite the degree of arthritis that was sustained equally at four weeks after inoculation, both DCE and SPE were back to control levels at that time. It can therefore be concluded that arthritis from a single joint is sufficient to elicit changes in CSF convertase activities, and that these effects disappear between 2 and 4 weeks after injection, although the arthritis persists.", "contents": "Decreased cerebrospinal fluid neuropeptide-converting enzyme activity in monoarthritic rats. The activity in rat cerebrospinal fluid (CSF) of dynorphin-converting enzyme (DCE) and substance P endopeptidase (SPE) was determined in control animals and in rats with monoarthritis. Enzymatic activities were measured with specific radioimmunoassays toward the N-terminal products Leu-enkephalin-Arg6 and substance P1-7, respectively. A monoarthritis stable during weeks 2-6 post-injection was induced by injection (0.05 ml) into one joint with Freund's adjuvant. Both SPE and DCE were significantly decreased 15 days after the intraarticular injection. Despite the degree of arthritis that was sustained equally at four weeks after inoculation, both DCE and SPE were back to control levels at that time. It can therefore be concluded that arthritis from a single joint is sufficient to elicit changes in CSF convertase activities, and that these effects disappear between 2 and 4 weeks after injection, although the arthritis persists."} {"id": "PMID:1279477", "title": "Regional differences in the distribution of capsaicin-sensitive target-identified adult rat dorsal root ganglion neurons.", "content": "A retrograde labelling technique combined with a cobalt uptake assay in cultured adult rat dorsal root ganglion (DRG) neurons were applied to study the distribution of capsaicin sensitivity in relation to different peripheral targets. This study shows that there are regional differences between skin, skeletal muscle and urinary bladder; 20-30% of skin afferents, 40% of muscle afferents and 60% of bladder afferents were found to be capsaicin-senditive. This may reflect differences in the proportion of chemosensitive afferents innervating different peripheral tissues.", "contents": "Regional differences in the distribution of capsaicin-sensitive target-identified adult rat dorsal root ganglion neurons. A retrograde labelling technique combined with a cobalt uptake assay in cultured adult rat dorsal root ganglion (DRG) neurons were applied to study the distribution of capsaicin sensitivity in relation to different peripheral targets. This study shows that there are regional differences between skin, skeletal muscle and urinary bladder; 20-30% of skin afferents, 40% of muscle afferents and 60% of bladder afferents were found to be capsaicin-senditive. This may reflect differences in the proportion of chemosensitive afferents innervating different peripheral tissues."} {"id": "PMID:1279478", "title": "Blockade of nitric oxide formation does not prevent glutamate-induced neurotoxicity in neuronal cultures from rat hippocampus.", "content": "This study examined the role of nitric oxide (NO) in glutamate-induced, N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity in rat hippocampal neuronal cultures grown under serum-free conditions. Formation of cGMP was used as an indirect measure of NO formation. Neuronal cell degeneration was monitored by measuring the release of lactate dehydrogenase (LDH). Neuronal cells showed a 4-fold increase in cGMP formation and release of LDH upon exposure to 30 microM glutamate. cGMP formation was fully inhibited by 1 microM nitro-arginine (N-Arg), 100 microM hemoglobin or 1 microM MK-801. In the presence of 1 microM MK-801, glutamate induced neither cGMP formation nor neuronal cell degeneration. However, when NO formation was inhibited by means of 100 microM N-Arg, glutamate still induced neurotoxicity. Therefore, in serum-free hippocampal cultures glutamate neurotoxicity occurs notwithstanding complete inhibition of the NO-synthase enzyme by N-Arg. Our data provide evidence that NO, synthesized upon glutamate exposure, has not a primary toxic action in pure hippocampal neuronal cultures.", "contents": "Blockade of nitric oxide formation does not prevent glutamate-induced neurotoxicity in neuronal cultures from rat hippocampus. This study examined the role of nitric oxide (NO) in glutamate-induced, N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity in rat hippocampal neuronal cultures grown under serum-free conditions. Formation of cGMP was used as an indirect measure of NO formation. Neuronal cell degeneration was monitored by measuring the release of lactate dehydrogenase (LDH). Neuronal cells showed a 4-fold increase in cGMP formation and release of LDH upon exposure to 30 microM glutamate. cGMP formation was fully inhibited by 1 microM nitro-arginine (N-Arg), 100 microM hemoglobin or 1 microM MK-801. In the presence of 1 microM MK-801, glutamate induced neither cGMP formation nor neuronal cell degeneration. However, when NO formation was inhibited by means of 100 microM N-Arg, glutamate still induced neurotoxicity. Therefore, in serum-free hippocampal cultures glutamate neurotoxicity occurs notwithstanding complete inhibition of the NO-synthase enzyme by N-Arg. Our data provide evidence that NO, synthesized upon glutamate exposure, has not a primary toxic action in pure hippocampal neuronal cultures."} {"id": "PMID:1279479", "title": "Colocalization of nitric oxide synthase and NADPH-diaphorase in the myenteric plexus of the rat gut.", "content": "The pattern of distribution and colocalization of nitric oxide-synthase (NOS) and NADPH-diaphorase in the myenteric plexus of whole-mount preparations of the antrum, duodenum, ileum, caecum, proximal colon and distal colon of the rat were investigated using immunohistochemical and histochemical staining techniques. Almost all the myenteric neurons that were NOS-positive in all regions of the gut examined were also stained for NADPH-diaphorase. However, in the stomach, duodenum and ileum, only a few of the NOS-positive nerve fibres in the tertiary and secondary plexuses and circular muscle layer were also stained for NADPH-diaphorase, whereas in the caecum and distal colon almost all the NOS-positive nerve fibres were also stained for NADPH-diaphorase. The results in the present study are consistent with the view that nitric oxide (NO) has a mediating role in gastrointestinal neurotransmission.", "contents": "Colocalization of nitric oxide synthase and NADPH-diaphorase in the myenteric plexus of the rat gut. The pattern of distribution and colocalization of nitric oxide-synthase (NOS) and NADPH-diaphorase in the myenteric plexus of whole-mount preparations of the antrum, duodenum, ileum, caecum, proximal colon and distal colon of the rat were investigated using immunohistochemical and histochemical staining techniques. Almost all the myenteric neurons that were NOS-positive in all regions of the gut examined were also stained for NADPH-diaphorase. However, in the stomach, duodenum and ileum, only a few of the NOS-positive nerve fibres in the tertiary and secondary plexuses and circular muscle layer were also stained for NADPH-diaphorase, whereas in the caecum and distal colon almost all the NOS-positive nerve fibres were also stained for NADPH-diaphorase. The results in the present study are consistent with the view that nitric oxide (NO) has a mediating role in gastrointestinal neurotransmission."} {"id": "PMID:1279480", "title": "Nitric oxide synthase immunoreactivity and NADPH-diaphorase activity in a subpopulation of intrinsic neurones of the guinea-pig heart.", "content": "This is the first report of the presence of nitric oxide synthase (NOS) immunoreactivity and NADPH-diaphorase (NADPH-d) activity in a subpopulation of the intrinsic neurones that innervate the heart. A cytochemical technique to detect NADPH-d and antisera raised against purified rat cerebellar NOS were employed to examine the expression of these enzymes by cells in a dissociated cell culture preparation from newborn guinea-pig atria and interatrial septum. Comparison of the results obtained by these two techniques and double-labelling experiments indicate that a subpopulation of intracardiac neurones contain both NADPH-d and NOS. These results indicate that some intracardiac neurones are capable of synthesizing nitric oxide. This raises the possibility that nitric oxide plays a role in the neural control of the heart.", "contents": "Nitric oxide synthase immunoreactivity and NADPH-diaphorase activity in a subpopulation of intrinsic neurones of the guinea-pig heart. This is the first report of the presence of nitric oxide synthase (NOS) immunoreactivity and NADPH-diaphorase (NADPH-d) activity in a subpopulation of the intrinsic neurones that innervate the heart. A cytochemical technique to detect NADPH-d and antisera raised against purified rat cerebellar NOS were employed to examine the expression of these enzymes by cells in a dissociated cell culture preparation from newborn guinea-pig atria and interatrial septum. Comparison of the results obtained by these two techniques and double-labelling experiments indicate that a subpopulation of intracardiac neurones contain both NADPH-d and NOS. These results indicate that some intracardiac neurones are capable of synthesizing nitric oxide. This raises the possibility that nitric oxide plays a role in the neural control of the heart."} {"id": "PMID:1279482", "title": "The polyamine diaminodecane (DA-10) produces a voltage-dependent flickery block of single NMDA receptor channels.", "content": "Receptor binding assays have shown that diaminodecane (DA-10) reduced binding of open channel blockers to the N-methyl-D-aspartate (NMDA) subtype of postsynaptic glutamate receptor through an interaction with the polyamine regulatory site. Because the action of DA-10 was opposite to that of the polyamine agonist spermine and was reversed by polyamine antagonists, DA-10 has been classified as an inverse agonist at the polyamine site. Using whole-cell voltage-clamp and single-channel recordings from cultured rat cortical neurons, we show that at negative holding potentials DA-10 (1-300 microM) reduced NMDA receptor whole cell current (IC50 = 34 microM) and produced a flickery block of NMDA single-channel currents. The flickery block of NMDA single channels was voltage-dependent and not reversed by the polyamine antagonist diethylenetriamine (DET). Potential mechanisms for the flickery block of NMDA single channel currents are discussed.", "contents": "The polyamine diaminodecane (DA-10) produces a voltage-dependent flickery block of single NMDA receptor channels. Receptor binding assays have shown that diaminodecane (DA-10) reduced binding of open channel blockers to the N-methyl-D-aspartate (NMDA) subtype of postsynaptic glutamate receptor through an interaction with the polyamine regulatory site. Because the action of DA-10 was opposite to that of the polyamine agonist spermine and was reversed by polyamine antagonists, DA-10 has been classified as an inverse agonist at the polyamine site. Using whole-cell voltage-clamp and single-channel recordings from cultured rat cortical neurons, we show that at negative holding potentials DA-10 (1-300 microM) reduced NMDA receptor whole cell current (IC50 = 34 microM) and produced a flickery block of NMDA single-channel currents. The flickery block of NMDA single channels was voltage-dependent and not reversed by the polyamine antagonist diethylenetriamine (DET). Potential mechanisms for the flickery block of NMDA single channel currents are discussed."} {"id": "PMID:1279483", "title": "Selective potentiation of GABA-mediated Cl- current by lanthanum ion in subtypes of cloned GABAA receptors.", "content": "The effect of lanthanum ion (La3+) on gamma-aminobutyric acid (GABA)-mediated Cl- currents was examined in the alpha 1 beta 2 or alpha 1 beta 2 gamma 2 subtype of GABAA receptors expressed in a human kidney cell line (A293), using a whole-cell configuration of patch-clamp techniques. La3+ dose-dependently stimulated the Cl- currents in the alpha 1 beta 2 gamma 2 subtype with an EC50 of 21.3 +/- 3.5 microM with a maximal potentiation of 240 +/- 16% as normalized to the GABA response at 5 microM. In the alpha 1 beta 2 subtype, however, the ion marginally potentiated GABA response, a maximal stimulation being less than 70% with an EC50 for La3+ near 200 microM. The stimulation of GABA response by La3+ in the alpha 1 beta 2 gamma 2 subtype was due to a decrease in the half maximal concentration for GABA and was more pronounced at the negative membrane potentials. This selectivity of La3+ toward the subtypes of GABAA receptors contrasts to that of Zn2+ which inhibits the currents in the alpha 1 beta 2, but not in the alpha 1 beta 2 gamma 2 subtype (Neuron, 5: (1990) 781-788). It appears that these polyvalent cations are useful in understanding the molecular basis for the functional diversity and in characterizing the molecular organization of native GABAA receptors.", "contents": "Selective potentiation of GABA-mediated Cl- current by lanthanum ion in subtypes of cloned GABAA receptors. The effect of lanthanum ion (La3+) on gamma-aminobutyric acid (GABA)-mediated Cl- currents was examined in the alpha 1 beta 2 or alpha 1 beta 2 gamma 2 subtype of GABAA receptors expressed in a human kidney cell line (A293), using a whole-cell configuration of patch-clamp techniques. La3+ dose-dependently stimulated the Cl- currents in the alpha 1 beta 2 gamma 2 subtype with an EC50 of 21.3 +/- 3.5 microM with a maximal potentiation of 240 +/- 16% as normalized to the GABA response at 5 microM. In the alpha 1 beta 2 subtype, however, the ion marginally potentiated GABA response, a maximal stimulation being less than 70% with an EC50 for La3+ near 200 microM. The stimulation of GABA response by La3+ in the alpha 1 beta 2 gamma 2 subtype was due to a decrease in the half maximal concentration for GABA and was more pronounced at the negative membrane potentials. This selectivity of La3+ toward the subtypes of GABAA receptors contrasts to that of Zn2+ which inhibits the currents in the alpha 1 beta 2, but not in the alpha 1 beta 2 gamma 2 subtype (Neuron, 5: (1990) 781-788). It appears that these polyvalent cations are useful in understanding the molecular basis for the functional diversity and in characterizing the molecular organization of native GABAA receptors."} {"id": "PMID:1279484", "title": "Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid.", "content": "In freshly isolated spinal dorsal horn (DH) neurons (laminae I-IV) of the young rat the effects of 25-100 microM of (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD), 1S,3R-ACPD and 1R,3S-ACPD, a metabotropic glutamate receptor (mGluR) agonist, on inward currents induced by glutamate (Glu), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate were studied under whole-cell voltage-clamp conditions. When the cells were clamped to -60 mV, the racemic mixture and both stereo isomers of trans-ACPD increase the responses elicited by Glu, AMPA, and NMDA, but little those of kainate. In addition, quisqualate (10-50 microM), in the presence of CNQX (5-20 microM) or NBQX (5 microM), potentiated NMDA-induced currents. The enhancing effect lasted 10-75 min, depending upon both dose and length of application. In a smaller proportion of dorsal horn neurons, the enhancing effect was preceded by a transient depression of the responses to Glu, AMPA, and NMDA. 2-Amino-3-phosphonopropionic acid (L-AP3), a putative antagonist of mGluR exerted little effect on responses to AMPA itself, but reduced or prevented the enhancing effect of 1S,3R-ACPD. It is concluded that activation of a metabotropic glutamate receptor by trans-ACPD, and its two enantiomers, may mediate the enhancement of AMPA and NMDA responses in acutely isolated rat spinal dorsal horn neurons. These results are consistent with the possibility that the activation of metabotropic glutamate receptor may contribute to the regulation of the strength of excitatory amino-mediated primary afferent neurotransmission, including nociception.", "contents": "Modulation of AMPA and NMDA responses in rat spinal dorsal horn neurons by trans-1-aminocyclopentane-1,3-dicarboxylic acid. In freshly isolated spinal dorsal horn (DH) neurons (laminae I-IV) of the young rat the effects of 25-100 microM of (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD), 1S,3R-ACPD and 1R,3S-ACPD, a metabotropic glutamate receptor (mGluR) agonist, on inward currents induced by glutamate (Glu), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), N-methyl-D-aspartate (NMDA) and kainate were studied under whole-cell voltage-clamp conditions. When the cells were clamped to -60 mV, the racemic mixture and both stereo isomers of trans-ACPD increase the responses elicited by Glu, AMPA, and NMDA, but little those of kainate. In addition, quisqualate (10-50 microM), in the presence of CNQX (5-20 microM) or NBQX (5 microM), potentiated NMDA-induced currents. The enhancing effect lasted 10-75 min, depending upon both dose and length of application. In a smaller proportion of dorsal horn neurons, the enhancing effect was preceded by a transient depression of the responses to Glu, AMPA, and NMDA. 2-Amino-3-phosphonopropionic acid (L-AP3), a putative antagonist of mGluR exerted little effect on responses to AMPA itself, but reduced or prevented the enhancing effect of 1S,3R-ACPD. It is concluded that activation of a metabotropic glutamate receptor by trans-ACPD, and its two enantiomers, may mediate the enhancement of AMPA and NMDA responses in acutely isolated rat spinal dorsal horn neurons. These results are consistent with the possibility that the activation of metabotropic glutamate receptor may contribute to the regulation of the strength of excitatory amino-mediated primary afferent neurotransmission, including nociception."} {"id": "PMID:1279485", "title": "Patterns of termination of cerebellar and basal ganglia efferents in the rat thalamus. Strictly segregated and partly overlapping projections.", "content": "There is a widely held view that the cerebellum and basal ganglia act via separate subcortical channels. In rodent, however, electrophysiological evidence suggests that the output of these two systems is partly sent to a common set of thalamic neurons. In this study, the pattern of thalamic innervations provided by the deep cerebellar nuclei, the entopeduncular nucleus, and the substantia nigra pars reticulata was reinvestigated in the rat using the anterograde tracers Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin. Although the results confirm the existence of some overlap in the cerebellar and basal ganglia projection fields, they also show that in such convergent areas the cerebellar innervation is modest and consists of sparsely distributed fibers of thin diameter that provide a few scattered terminal boutons. These observations are consistent with the view that, in rodent as in higher mammalian species, the cerebellum and the basal ganglia act mainly via distinct thalamo-cortical channels.", "contents": "Patterns of termination of cerebellar and basal ganglia efferents in the rat thalamus. Strictly segregated and partly overlapping projections. There is a widely held view that the cerebellum and basal ganglia act via separate subcortical channels. In rodent, however, electrophysiological evidence suggests that the output of these two systems is partly sent to a common set of thalamic neurons. In this study, the pattern of thalamic innervations provided by the deep cerebellar nuclei, the entopeduncular nucleus, and the substantia nigra pars reticulata was reinvestigated in the rat using the anterograde tracers Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin. Although the results confirm the existence of some overlap in the cerebellar and basal ganglia projection fields, they also show that in such convergent areas the cerebellar innervation is modest and consists of sparsely distributed fibers of thin diameter that provide a few scattered terminal boutons. These observations are consistent with the view that, in rodent as in higher mammalian species, the cerebellum and the basal ganglia act mainly via distinct thalamo-cortical channels."} {"id": "PMID:1279486", "title": "Adenosine inhibits action potential-dependent release of calcitonin gene-related peptide- and substance P-like immunoreactivities from primary afferents in rat spinal cord.", "content": "Electrical field stimulation (5 Hz) evoked a prompt outflow of calcitonin gene-related peptide- and substance P-like immunoreactivities (CGRP-LI and SP-LI, respectively) from superfused slices of the dorsal but not ventral half of the rat spinal cord. The evoked outflow was abolished by tetrodotoxin, calcium-free medium or previous exposure to capsaicin, indicating that it is produced through action potentials invading the central terminals of capsaicin-sensitive primary afferents. Adenosine as well as gamma-aminobutyric acid (GABA) or the GABAB receptor agonist (-)-baclofen produced a concentration-dependent inhibition of the evoked CGRP-LI outflow. Adenosine also inhibited the evoked SP-LI outflow. These findings demonstrate that inhibition of transmitter release from primary afferent neurons should be considered as a possible mechanism of the antinociceptive action of adenosine and adenosine analogs.", "contents": "Adenosine inhibits action potential-dependent release of calcitonin gene-related peptide- and substance P-like immunoreactivities from primary afferents in rat spinal cord. Electrical field stimulation (5 Hz) evoked a prompt outflow of calcitonin gene-related peptide- and substance P-like immunoreactivities (CGRP-LI and SP-LI, respectively) from superfused slices of the dorsal but not ventral half of the rat spinal cord. The evoked outflow was abolished by tetrodotoxin, calcium-free medium or previous exposure to capsaicin, indicating that it is produced through action potentials invading the central terminals of capsaicin-sensitive primary afferents. Adenosine as well as gamma-aminobutyric acid (GABA) or the GABAB receptor agonist (-)-baclofen produced a concentration-dependent inhibition of the evoked CGRP-LI outflow. Adenosine also inhibited the evoked SP-LI outflow. These findings demonstrate that inhibition of transmitter release from primary afferent neurons should be considered as a possible mechanism of the antinociceptive action of adenosine and adenosine analogs."} {"id": "PMID:1279487", "title": "A-current in rat globus pallidus: a whole-cell voltage clamp study on acutely dissociated neurons.", "content": "Globus pallidus neurons were dissociated from adult rats and recorded in whole-cell voltage-clamp mode. In tetrodotoxin- and cadmium-added bath, outward potassium conductances were evaluated. Depolarization activated large and predominantly sustained currents, with little inactivation. The transient outward current was isolated through its voltage-dependency, kinetics and pharmacology. A-like current activated around -45 mV and decayed exponentially with a time-constant of about 50 ms at 0 mV. Steady-state half-inactivation voltage was about -60 mV, suggesting that A-current was not fully inactivated at rest. 4-Aminopyridine sensitivity of the transient outward current was in the low millimolar range. A-current might play a relevant role in shaping firing properties of pallidal neurons.", "contents": "A-current in rat globus pallidus: a whole-cell voltage clamp study on acutely dissociated neurons. Globus pallidus neurons were dissociated from adult rats and recorded in whole-cell voltage-clamp mode. In tetrodotoxin- and cadmium-added bath, outward potassium conductances were evaluated. Depolarization activated large and predominantly sustained currents, with little inactivation. The transient outward current was isolated through its voltage-dependency, kinetics and pharmacology. A-like current activated around -45 mV and decayed exponentially with a time-constant of about 50 ms at 0 mV. Steady-state half-inactivation voltage was about -60 mV, suggesting that A-current was not fully inactivated at rest. 4-Aminopyridine sensitivity of the transient outward current was in the low millimolar range. A-current might play a relevant role in shaping firing properties of pallidal neurons."} {"id": "PMID:1279488", "title": "Normal serotonin but elevated 5-hydroxyindoleacetic acid concentration in cerebellar cortex of patients with dominantly-inherited olivopontocerebellar atrophy.", "content": "Beas-Zarate and coworkers (Eur. J. Pharmacol., 198 (1991) 7-14) recently reported markedly reduced concentration of presynaptic serotonin neurotransmitter markers in cerebellum of rodents which had suffered destruction of the inferior olivary-cerebellar (climbing fibre) projections by the neurotoxin 3-acetylpyridine; these experimental animal data suggested that serotonin might be one of the neurotransmitters released by climbing fibres. We measured the concentration of serotonin and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in autopsied cerebellar cortex of 14 patients with dominantly-inherited olivopontocerebellar atrophy (OPCA) who all had near-total degeneration of the inferior olivary climbing fibres. As compared with the controls, mean concentration of serotonin in cerebellar cortex of the OPCA patients was normal whereas 5-HIAA levels (+79%, P less than 0.02) and 'turnover' ratio 5-HIAA/serotonin (+148%, P less than 0.05), on average, were significantly elevated. These data do not support the notion that serotonin is a predominant neurotransmitter of the human climbing fibre. However, the markedly elevated serotonin turnover ratio suggests the possibility of increased serotonergic neuronal activity, which might alter, and perhaps improve, the functioning of the preserved cerebellar cortical neurones in OPCA.", "contents": "Normal serotonin but elevated 5-hydroxyindoleacetic acid concentration in cerebellar cortex of patients with dominantly-inherited olivopontocerebellar atrophy. Beas-Zarate and coworkers (Eur. J. Pharmacol., 198 (1991) 7-14) recently reported markedly reduced concentration of presynaptic serotonin neurotransmitter markers in cerebellum of rodents which had suffered destruction of the inferior olivary-cerebellar (climbing fibre) projections by the neurotoxin 3-acetylpyridine; these experimental animal data suggested that serotonin might be one of the neurotransmitters released by climbing fibres. We measured the concentration of serotonin and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in autopsied cerebellar cortex of 14 patients with dominantly-inherited olivopontocerebellar atrophy (OPCA) who all had near-total degeneration of the inferior olivary climbing fibres. As compared with the controls, mean concentration of serotonin in cerebellar cortex of the OPCA patients was normal whereas 5-HIAA levels (+79%, P less than 0.02) and 'turnover' ratio 5-HIAA/serotonin (+148%, P less than 0.05), on average, were significantly elevated. These data do not support the notion that serotonin is a predominant neurotransmitter of the human climbing fibre. However, the markedly elevated serotonin turnover ratio suggests the possibility of increased serotonergic neuronal activity, which might alter, and perhaps improve, the functioning of the preserved cerebellar cortical neurones in OPCA."} {"id": "PMID:1279489", "title": "Tetanus toxin alters 5-hydroxytryptamine, dopamine, and their metabolites in rat hippocampus measured by in vivo microdialysis.", "content": "Tetanus toxin is a potent neurotoxin, the mode of action of which is unknown, although it is widely considered to be mediated by loss of inhibitory neurotransmission. In the present study we have investigated the effect of a single unilateral injection of tetanus toxin in the hippocampus on extracellular concentrations of 5-hydroxytryptamine (5-HT), dopamine and their metabolites in freely moving rats. Tetanus toxin treatment caused a progressive decline in hippocampal dialysate 5-hydroxytryptamine over the 3-day period following the injection. After 3 days the level of 5-HT on the injected side was only 20% of the control side. On the second day of observation the level of dopamine was found to be elevated by more than 2-fold but this was not the case for either of the other 2 days studied. The 5-hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid declined in a manner similar to that of the parent transmitter, but to a lesser extent. Of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid was decreased on the second and third days of observation, whilst homovanillic acid was not significantly altered during the period of observation.", "contents": "Tetanus toxin alters 5-hydroxytryptamine, dopamine, and their metabolites in rat hippocampus measured by in vivo microdialysis. Tetanus toxin is a potent neurotoxin, the mode of action of which is unknown, although it is widely considered to be mediated by loss of inhibitory neurotransmission. In the present study we have investigated the effect of a single unilateral injection of tetanus toxin in the hippocampus on extracellular concentrations of 5-hydroxytryptamine (5-HT), dopamine and their metabolites in freely moving rats. Tetanus toxin treatment caused a progressive decline in hippocampal dialysate 5-hydroxytryptamine over the 3-day period following the injection. After 3 days the level of 5-HT on the injected side was only 20% of the control side. On the second day of observation the level of dopamine was found to be elevated by more than 2-fold but this was not the case for either of the other 2 days studied. The 5-hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid declined in a manner similar to that of the parent transmitter, but to a lesser extent. Of the dopamine metabolites, 3,4-dihydroxyphenylacetic acid was decreased on the second and third days of observation, whilst homovanillic acid was not significantly altered during the period of observation."} {"id": "PMID:1279491", "title": "Effects of chlordecone on food intake and body weight in the male rat.", "content": "The effects of the chlorinated pesticide chlordecone on food intake, body weight, and water intake were examined in adult male rats. Chlordecone treatment produced a dose dependent suppression of food intake. Loss of body weight accompanied the reduced food intake. However, chlordecone did not suppress water intake. Chlordecone treated animals maintained on a liquid diet also demonstrated reduced food intake, suggesting that chlordecone has a specific effect on feeding behavior and not a general effect on ingestive behaviors. The potential contribution of chlordecone-induced tremor to the suppressed food intake and the loss of body weight was considered. When treatment occurred immediately before a 24 hr fast, controls and animals given 75 mg/kg showed no differences in the body weight decline, even though tremor occurred in the pesticide-treated rats. Thus, it is unlikely that tremor alone produced the body weight loss observed in the present experiment. Similarly, animals were capable of initiating eating behavior even though tremor was present. In addition, chlordecone treatment inhibited food intake within 2 hr. Consequently, these results suggest that chlordecone suppresses food intake which in turn produces the decline in body weight.", "contents": "Effects of chlordecone on food intake and body weight in the male rat. The effects of the chlorinated pesticide chlordecone on food intake, body weight, and water intake were examined in adult male rats. Chlordecone treatment produced a dose dependent suppression of food intake. Loss of body weight accompanied the reduced food intake. However, chlordecone did not suppress water intake. Chlordecone treated animals maintained on a liquid diet also demonstrated reduced food intake, suggesting that chlordecone has a specific effect on feeding behavior and not a general effect on ingestive behaviors. The potential contribution of chlordecone-induced tremor to the suppressed food intake and the loss of body weight was considered. When treatment occurred immediately before a 24 hr fast, controls and animals given 75 mg/kg showed no differences in the body weight decline, even though tremor occurred in the pesticide-treated rats. Thus, it is unlikely that tremor alone produced the body weight loss observed in the present experiment. Similarly, animals were capable of initiating eating behavior even though tremor was present. In addition, chlordecone treatment inhibited food intake within 2 hr. Consequently, these results suggest that chlordecone suppresses food intake which in turn produces the decline in body weight."} {"id": "PMID:1279492", "title": "Changes of fast axonal transport by taxol injected subepineurally into the rat sciatic nerve.", "content": "In contrast to the complete and long-lasting inhibition of tubulin transport, taxol has no effect on fast axonal transport examined immediately after its sub-epineural application to rat sciatic nerve. However, a significant accumulation of rapidly migrating radioactivity appears at the site proximal to the injection when examined a few weeks after treatment, probably due to mechanical obstruction caused by abnormal aggregation of a huge number of intra-axonal microtubules. It also decreases slightly in amount within a few weeks post-treatment, which may be due to reduction of the number of axons caused by degeneration.", "contents": "Changes of fast axonal transport by taxol injected subepineurally into the rat sciatic nerve. In contrast to the complete and long-lasting inhibition of tubulin transport, taxol has no effect on fast axonal transport examined immediately after its sub-epineural application to rat sciatic nerve. However, a significant accumulation of rapidly migrating radioactivity appears at the site proximal to the injection when examined a few weeks after treatment, probably due to mechanical obstruction caused by abnormal aggregation of a huge number of intra-axonal microtubules. It also decreases slightly in amount within a few weeks post-treatment, which may be due to reduction of the number of axons caused by degeneration."} {"id": "PMID:1279493", "title": "The efficacy of serum prostate specific antigen as a tumour marker in prostatic carcinoma: a comparison with serum acid phosphatase.", "content": "To assess the efficacy of serum prostate specific antigen (PSA) in the diagnosis of prostatic cancer. To compare this tumour marker with serum acid phosphatase (ACP) in order to define the more effective diagnostic test. Serum samples from 349 patients attending a urology department were assayed for PSA and ACP. Histological assessment of prostatic biopsy samples was used as the standard by which the diagnostic effectiveness of the tumour markers was determined. Mean serum PSA results from patients with prostatic carcinoma (159 (SEM 35) ng/mL) were significantly different to those from patients with benign prostatic hyperplasia (4.0 (0.53) ng/mL). As there was considerable overlap of results, test sensitivities and specificities were calculated for various decision points. The sensitivity and specificity of PSA at a level of 10 ng/mL were 61.2% and 93.0% respectively, while for ACP at a level of 0.8 U/L they were 47.6% and 89.9%. The areas beneath receiver-operator curves (0.81 for PSA and 0.72 for ACP) indicated that PSA gives better diagnostic information than ACP. For a stated incidence of cancer, posttest probabilities following a given PSA result have been calculated. PSA is a more effective serum marker for prostatic carcinoma than ACP. We present a table so that for similar patient groups posttest probabilities for prostatic cancer can be assessed for a given serum PSA level.", "contents": "The efficacy of serum prostate specific antigen as a tumour marker in prostatic carcinoma: a comparison with serum acid phosphatase. To assess the efficacy of serum prostate specific antigen (PSA) in the diagnosis of prostatic cancer. To compare this tumour marker with serum acid phosphatase (ACP) in order to define the more effective diagnostic test. Serum samples from 349 patients attending a urology department were assayed for PSA and ACP. Histological assessment of prostatic biopsy samples was used as the standard by which the diagnostic effectiveness of the tumour markers was determined. Mean serum PSA results from patients with prostatic carcinoma (159 (SEM 35) ng/mL) were significantly different to those from patients with benign prostatic hyperplasia (4.0 (0.53) ng/mL). As there was considerable overlap of results, test sensitivities and specificities were calculated for various decision points. The sensitivity and specificity of PSA at a level of 10 ng/mL were 61.2% and 93.0% respectively, while for ACP at a level of 0.8 U/L they were 47.6% and 89.9%. The areas beneath receiver-operator curves (0.81 for PSA and 0.72 for ACP) indicated that PSA gives better diagnostic information than ACP. For a stated incidence of cancer, posttest probabilities following a given PSA result have been calculated. PSA is a more effective serum marker for prostatic carcinoma than ACP. We present a table so that for similar patient groups posttest probabilities for prostatic cancer can be assessed for a given serum PSA level."} {"id": "PMID:1279494", "title": "Upper gastrointestinal endoscopy in patients with human immunodeficiency virus infection: is it worthwhile?", "content": "To determine the diagnostic accuracy of upper gastrointestinal endoscopy in a selected group of patients with HIV infection, who had severe symptoms unresponsive to empirical treatment. We reviewed all patients with HIV infection, who had undergone upper gastrointestinal endoscopy at Auckland Hospital. Specific diagnoses were based on the endoscopic appearances and on the histological and microbiological examination of endoscopic biopsies taken from the oesophagus, stomach and duodenum. A definitive diagnosis was reached in 16 of the 21 patients endoscoped, of whom 13 had a good clinical response to treatment. The median survival was three months. The most common diagnosis was oesophageal candidiasis seen in six patients, all of whom responded to treatment with a median survival of six months. Invasive cytomegalovirus gastrointestinal disease was seen in three patients, none of whom had positive blood cultures for cytomegalovirus. All responded to intravenous ganciclovir. Three patients with severe diarrhoea had opportunistic infection of the small bowel. All three had advanced AIDS with a median survival of less than one month. Upper gastrointestinal endoscopy has a high diagnostic yield in patients with HIV infection with oesophageal symptoms which fail to respond to antifungal therapy, or with severe weight loss and diarrhoea and it should be considered in these patients because excellent palliation may be possible.", "contents": "Upper gastrointestinal endoscopy in patients with human immunodeficiency virus infection: is it worthwhile? To determine the diagnostic accuracy of upper gastrointestinal endoscopy in a selected group of patients with HIV infection, who had severe symptoms unresponsive to empirical treatment. We reviewed all patients with HIV infection, who had undergone upper gastrointestinal endoscopy at Auckland Hospital. Specific diagnoses were based on the endoscopic appearances and on the histological and microbiological examination of endoscopic biopsies taken from the oesophagus, stomach and duodenum. A definitive diagnosis was reached in 16 of the 21 patients endoscoped, of whom 13 had a good clinical response to treatment. The median survival was three months. The most common diagnosis was oesophageal candidiasis seen in six patients, all of whom responded to treatment with a median survival of six months. Invasive cytomegalovirus gastrointestinal disease was seen in three patients, none of whom had positive blood cultures for cytomegalovirus. All responded to intravenous ganciclovir. Three patients with severe diarrhoea had opportunistic infection of the small bowel. All three had advanced AIDS with a median survival of less than one month. Upper gastrointestinal endoscopy has a high diagnostic yield in patients with HIV infection with oesophageal symptoms which fail to respond to antifungal therapy, or with severe weight loss and diarrhoea and it should be considered in these patients because excellent palliation may be possible."} {"id": "PMID:1279495", "title": "Conjunctival mast cells and the allergic late phase reaction.", "content": "An active model of ocular anaphylaxis was developed in guinea pigs to evaluate the histopathology of the early (EPR) and late (LPR) phase reaction, focusing on the role of mast cells. Five groups (n = 6) of animals were actively immunized by first injecting into each of the axillary and inguinal lymph node areas, 0.25 ml of an emulsion containing 1 mg dinitrophenyl bovine gamma-globulin (DNP-BCG) with 0.5 ml complete Freund's adjuvant. After two weeks, an intramuscular injection of 0.5 ml of an emulsion containing 1 mg DNP-BGG with 0.5 ml of incomplete adjuvant was administered. One month after the first injection, animals were sacrificed after topical ocular challenge with 10 microliters of 1 mg/ml divalent hapten, di-DNP-lysine, in one eye and phosphate buffered saline (PBS) in the fellow eye as control. Clinical reactions were graded over time and histology evaluated at the endpoint (time 0, 0.5, 3, 9, and 24 h). Results showed that all animals clearly developed both an EPR and an LPR, as either a biphasic, multiphasic or prolonged clinical response. A small percentage of mast cells were degranulated at baseline, whereas, at 0.5 h, 95% of mast cells were degranulated in the eyes treated with specific hapten and 25% in the control eyes treated with PBS. At 3 h, 84% of the mast cells were degranulated. This value rose to 89% at 9 h, and remained unchanged at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Conjunctival mast cells and the allergic late phase reaction. An active model of ocular anaphylaxis was developed in guinea pigs to evaluate the histopathology of the early (EPR) and late (LPR) phase reaction, focusing on the role of mast cells. Five groups (n = 6) of animals were actively immunized by first injecting into each of the axillary and inguinal lymph node areas, 0.25 ml of an emulsion containing 1 mg dinitrophenyl bovine gamma-globulin (DNP-BCG) with 0.5 ml complete Freund's adjuvant. After two weeks, an intramuscular injection of 0.5 ml of an emulsion containing 1 mg DNP-BGG with 0.5 ml of incomplete adjuvant was administered. One month after the first injection, animals were sacrificed after topical ocular challenge with 10 microliters of 1 mg/ml divalent hapten, di-DNP-lysine, in one eye and phosphate buffered saline (PBS) in the fellow eye as control. Clinical reactions were graded over time and histology evaluated at the endpoint (time 0, 0.5, 3, 9, and 24 h). Results showed that all animals clearly developed both an EPR and an LPR, as either a biphasic, multiphasic or prolonged clinical response. A small percentage of mast cells were degranulated at baseline, whereas, at 0.5 h, 95% of mast cells were degranulated in the eyes treated with specific hapten and 25% in the control eyes treated with PBS. At 3 h, 84% of the mast cells were degranulated. This value rose to 89% at 9 h, and remained unchanged at 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279496", "title": "Histopathology of smokeless tobacco lesions in professional baseball players. Associations with different types of tobacco.", "content": "We examined 142 biopsy specimens of smokeless tobacco-associated oral mucosal lesions from 133 professional baseball players. Four types of epithelial change were observed in the specimens: hyperparakeratosis, hyperorthokeratosis, pale surface staining, and basal cell hyperplasia. These types of epithelial change were associated with the type of smokeless tobacco used (snuff or chewing tobacco) but not with the duration (years) or amount (hours per day) of use. The thickness of hyperkeratosis in a specimen correlated directly with the amount of smokeless tobacco use. The use of snuff was more frequently associated with development of oral mucosal lesions than was the use of chewing tobacco, and snuff appeared to cause a greater variety and severity of epithelial change than did chewing tobacco.", "contents": "Histopathology of smokeless tobacco lesions in professional baseball players. Associations with different types of tobacco. We examined 142 biopsy specimens of smokeless tobacco-associated oral mucosal lesions from 133 professional baseball players. Four types of epithelial change were observed in the specimens: hyperparakeratosis, hyperorthokeratosis, pale surface staining, and basal cell hyperplasia. These types of epithelial change were associated with the type of smokeless tobacco used (snuff or chewing tobacco) but not with the duration (years) or amount (hours per day) of use. The thickness of hyperkeratosis in a specimen correlated directly with the amount of smokeless tobacco use. The use of snuff was more frequently associated with development of oral mucosal lesions than was the use of chewing tobacco, and snuff appeared to cause a greater variety and severity of epithelial change than did chewing tobacco."} {"id": "PMID:1279497", "title": "[The anti-androgen flutamide in the treatment of prostatic hyperplasia].", "content": "The authors treated 23 benign prostatic hyperplasia (BPH) patients with antiandrogen flutamide. Half of the patients were treated with 500 mg, the another part with 750 mg flutamide for three months, and after 3 months brake again for 3 months. The decrease of the residual urine and an increase of the flow were observed. The subjective parameters were improved, too. In some patients side effects (gynecomastia, loss of appetite and potency) were observed. There was no different in the effect of the two doses.", "contents": "[The anti-androgen flutamide in the treatment of prostatic hyperplasia]. The authors treated 23 benign prostatic hyperplasia (BPH) patients with antiandrogen flutamide. Half of the patients were treated with 500 mg, the another part with 750 mg flutamide for three months, and after 3 months brake again for 3 months. The decrease of the residual urine and an increase of the flow were observed. The subjective parameters were improved, too. In some patients side effects (gynecomastia, loss of appetite and potency) were observed. There was no different in the effect of the two doses."} {"id": "PMID:1279498", "title": "Transgenes encoding mutant simian virus 40 large T antigens unmask phenotypic and functional constraints in thymic epithelial cells.", "content": "Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin. Unexpectedly the human growth hormone-releasing factor (GRF) gene promoter directs expression of SV40 Tag specifically in thymic epithelial (TE) cells. Expression starts in the neonate, in which GRF-Tag+ cells display strict numerical and spatial constraints. Tag supersedes mechanisms that constrain these features and GRF-Tag mice develop thymic hyperplasia. To characterize GRF-Tag+ TE cells and their putative normal counterparts we compared phenotypic and functional effects caused by transgenes encoding mutant large T antigens. This strategy is applicable to any situation in which T antigen is used to alter development. One large Tag mutant (K1 + 5080) does not cause thymic hyperplasia. GRF-Tag (K1 + 5080)+ TE cells display strict temporal and spatial constraints throughout life. TE cells expressing other mutant large T antigens that cause thymic hyperplasia do not obey these rules and reveal that phenotypically distinct GRF-Tag+ TE-cell stages exist in vivo. Analysis of conditional immortal GRF-Tag(tsA58)+ TE cells expressing a temperature-sensitive large Tag shows that large Tag blocks differentiation in these cells. Phenotype and functions in these cells are regulated by cellular differentiation and interleukin 4 (IL-4).", "contents": "Transgenes encoding mutant simian virus 40 large T antigens unmask phenotypic and functional constraints in thymic epithelial cells. Transgenes encoding simian virus 40 (SV40) T antigen (Tag) can cause hyperplastic or tumorigenic lesions of desired but also of unforeseen cellular origin. Unexpectedly the human growth hormone-releasing factor (GRF) gene promoter directs expression of SV40 Tag specifically in thymic epithelial (TE) cells. Expression starts in the neonate, in which GRF-Tag+ cells display strict numerical and spatial constraints. Tag supersedes mechanisms that constrain these features and GRF-Tag mice develop thymic hyperplasia. To characterize GRF-Tag+ TE cells and their putative normal counterparts we compared phenotypic and functional effects caused by transgenes encoding mutant large T antigens. This strategy is applicable to any situation in which T antigen is used to alter development. One large Tag mutant (K1 + 5080) does not cause thymic hyperplasia. GRF-Tag (K1 + 5080)+ TE cells display strict temporal and spatial constraints throughout life. TE cells expressing other mutant large T antigens that cause thymic hyperplasia do not obey these rules and reveal that phenotypically distinct GRF-Tag+ TE-cell stages exist in vivo. Analysis of conditional immortal GRF-Tag(tsA58)+ TE cells expressing a temperature-sensitive large Tag shows that large Tag blocks differentiation in these cells. Phenotype and functions in these cells are regulated by cellular differentiation and interleukin 4 (IL-4)."} {"id": "PMID:1279499", "title": "Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene.", "content": "We have cloned and sequenced the human KIT proto-oncogene, which contains 21 exons and spans more than 34 kb of DNA on chromosome segment 4q12. We also establish physical linkage between the KIT gene and the related PDGFRA gene. The organization of the KIT gene is virtually identical to that of the homologous FMS gene, located on chromosome 5. Together, these data suggest that the KIT and PDGFRA genes on chromosome 4 and the FMS and PDGFRB genes on chromosome 5 arose by duplication of a common ancestral gene, followed by duplication of a chromosome.", "contents": "Organization and nucleotide sequence of the human KIT (mast/stem cell growth factor receptor) proto-oncogene. We have cloned and sequenced the human KIT proto-oncogene, which contains 21 exons and spans more than 34 kb of DNA on chromosome segment 4q12. We also establish physical linkage between the KIT gene and the related PDGFRA gene. The organization of the KIT gene is virtually identical to that of the homologous FMS gene, located on chromosome 5. Together, these data suggest that the KIT and PDGFRA genes on chromosome 4 and the FMS and PDGFRB genes on chromosome 5 arose by duplication of a common ancestral gene, followed by duplication of a chromosome."} {"id": "PMID:1279501", "title": "Effect of substance P on ciliary beat frequency in human adenoid explants.", "content": "This study investigated the direct effects of substance P (SP) on ciliary beat frequency of human upper airway mucosa. Human adenoid explant tissue was maintained in serum free culture media, MCDB153. Ciliated epithelial cells were observed with phase-contrast microscopy and ciliary activity was measured using a photometric technique. Oscillations in transmitted light caused by ciliary beating were recorded and modal ciliary beat frequency was determined by fast Fourier transformation. Specimens were treated with SP at concentrations of 10(-4), 10(-5), 10(-6), and 10(-7) mol/L and with equal molar solutions of SP and (D-Pro2,D-Trp7,9)-SP, a SP antagonist. Substance P was found to increase ciliary beat frequency in a dose-dependent manner with a maximum increase of 12.1%. This effect was not seen with solutions containing (D-Pro2,D-Trp7,9)-SP. This suggests that SP exerts a direct stimulatory effect on ciliated cells of the upper airway. Because SP is known to be released in the upper airway in response to chemical irritation, it is presumed that the stimulatory effect of SP on mucosal cells provides a protective mechanism against inhaled irritants.", "contents": "Effect of substance P on ciliary beat frequency in human adenoid explants. This study investigated the direct effects of substance P (SP) on ciliary beat frequency of human upper airway mucosa. Human adenoid explant tissue was maintained in serum free culture media, MCDB153. Ciliated epithelial cells were observed with phase-contrast microscopy and ciliary activity was measured using a photometric technique. Oscillations in transmitted light caused by ciliary beating were recorded and modal ciliary beat frequency was determined by fast Fourier transformation. Specimens were treated with SP at concentrations of 10(-4), 10(-5), 10(-6), and 10(-7) mol/L and with equal molar solutions of SP and (D-Pro2,D-Trp7,9)-SP, a SP antagonist. Substance P was found to increase ciliary beat frequency in a dose-dependent manner with a maximum increase of 12.1%. This effect was not seen with solutions containing (D-Pro2,D-Trp7,9)-SP. This suggests that SP exerts a direct stimulatory effect on ciliated cells of the upper airway. Because SP is known to be released in the upper airway in response to chemical irritation, it is presumed that the stimulatory effect of SP on mucosal cells provides a protective mechanism against inhaled irritants."} {"id": "PMID:1279502", "title": "Comparison of the vasoconstrictive and anesthetic effects of intranasally applied cocaine vs. xylometazoline/lidocaine solution.", "content": "Cocaine solution has traditionally been the agent of choice for vasoconstriction and anesthesia when applied topically to the nasal mucosa during nasal operative procedures. Because of the relative scarcity and resulting expense of cocaine, there has arisen an impetus for an alternative intranasal solution for mucosal anesthesia and vasoconstriction. As a logical alternative, we have used a mixed solution of xylometazoline and lidocaine with reasonable results. No clinical studies comparing the efficacy of the two solutions exist, however, and there is presently no such solution commercially available. A double-blind, randomized, placebo-controlled study was undertaken to assess the relative efficacy of the preparations. Both solutions resulted in a marked and roughly equivalent degree of mucosal vasoconstriction (as evidenced by comparable increases in nasal airway cross-sectional area). Subjective pain ratings of mucosal pin-prick decreased a surprisingly small degree after application of both solutions. It appears that xylometazoline/lidocaine solution is comparable to cocaine solution for purposes of vasoconstriction and anesthesia during intranasal operative procedures.", "contents": "Comparison of the vasoconstrictive and anesthetic effects of intranasally applied cocaine vs. xylometazoline/lidocaine solution. Cocaine solution has traditionally been the agent of choice for vasoconstriction and anesthesia when applied topically to the nasal mucosa during nasal operative procedures. Because of the relative scarcity and resulting expense of cocaine, there has arisen an impetus for an alternative intranasal solution for mucosal anesthesia and vasoconstriction. As a logical alternative, we have used a mixed solution of xylometazoline and lidocaine with reasonable results. No clinical studies comparing the efficacy of the two solutions exist, however, and there is presently no such solution commercially available. A double-blind, randomized, placebo-controlled study was undertaken to assess the relative efficacy of the preparations. Both solutions resulted in a marked and roughly equivalent degree of mucosal vasoconstriction (as evidenced by comparable increases in nasal airway cross-sectional area). Subjective pain ratings of mucosal pin-prick decreased a surprisingly small degree after application of both solutions. It appears that xylometazoline/lidocaine solution is comparable to cocaine solution for purposes of vasoconstriction and anesthesia during intranasal operative procedures."} {"id": "PMID:1279503", "title": "Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization.", "content": "Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein-Barr virus transformed B-cell lines (EBV-TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B-lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV-TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV-TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood-stage parasites when using high-resolution digitized video-intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques.", "contents": "Human monoclonal antibodies against Plasmodium falciparum: production, stabilization and characterization. Nine human monoclonal antibodies (MoAbs) recognizing 7 different antigenic structures of blood-stages of the human malarial parasite P. falciparum (Pf) were produced by Epstein-Barr virus transformed B-cell lines (EBV-TCL) with or without fusion to the lymphoblastoid cell line KR4. The peripheral blood B-lymphocytes were obtained from 8 Gambian donors immune to Pf malaria. Two of the EBV-TCL could be expanded and maintained for more than 6 months but neither one could be cloned. Six additional EBV-TCL were stabilized after fusion with the KR4 lymphoblastoid cell line. All resulting hybridomas permitted easy cloning. Some of the MoAbs produced distinct fluorescent staining patterns of asexual Pf blood-stage parasites when using high-resolution digitized video-intensified fluorescence microscopy. Antigens on 195 kD and 155 kD proteins were recognized by 3 and 1 MoAb, respectively, using Western blotting and immunoprecipitation techniques."} {"id": "PMID:1279504", "title": "Monoclonal antibodies recognize a processing dependent epitope present in the mature CS protein of various plasmodial species.", "content": "In the present paper, we have characterized the specificity of a series of monoclonal antibodies (MoAbs) against Plasmodium berghei sporozoites, selected for their lack of reactivity with the repeat domain of the circumsporozoite (CS) protein. We found that these MoAbs recognize Pb44, the mature membrane form of the CS protein, but they do not react with Pb54, its precursor. Furthermore, these MoAbs do not react with any of the synthetic peptides representing the linear sequence of the P. berghei CS protein nor do they react with a recombinant CS (rCS) protein. These observations indicate that the epitope recognized by these antibodies is expressed only after the processing of the CS protein has occurred. This 'processing dependent epitope' is present in sporozoites of P. berghei, and also in those of P. falciparum, P. yoelii and P. brasilianum. It is not present in sporozoites of the P. cynomolgi-P. vivax complex and of P. gallinaceum. These anti-sporozoite MoAbs strongly inhibit sporozoite invasion of hepatoma cells, in vitro, however, they displayed no protective effect in an in vivo assay.", "contents": "Monoclonal antibodies recognize a processing dependent epitope present in the mature CS protein of various plasmodial species. In the present paper, we have characterized the specificity of a series of monoclonal antibodies (MoAbs) against Plasmodium berghei sporozoites, selected for their lack of reactivity with the repeat domain of the circumsporozoite (CS) protein. We found that these MoAbs recognize Pb44, the mature membrane form of the CS protein, but they do not react with Pb54, its precursor. Furthermore, these MoAbs do not react with any of the synthetic peptides representing the linear sequence of the P. berghei CS protein nor do they react with a recombinant CS (rCS) protein. These observations indicate that the epitope recognized by these antibodies is expressed only after the processing of the CS protein has occurred. This 'processing dependent epitope' is present in sporozoites of P. berghei, and also in those of P. falciparum, P. yoelii and P. brasilianum. It is not present in sporozoites of the P. cynomolgi-P. vivax complex and of P. gallinaceum. These anti-sporozoite MoAbs strongly inhibit sporozoite invasion of hepatoma cells, in vitro, however, they displayed no protective effect in an in vivo assay."} {"id": "PMID:1279505", "title": "An evaluation of the role of carbohydrate epitopes in immunity to Trichinella spiralis.", "content": "A study is described in which the role of carbohydrate epitopes in the generation of protective immunity to Trichinella spiralis was investigated. Antigen preparations were treated with increasing molar concentrations of sodium periodate, which is known to degrade carbohydrate moieties by cleaving one side of the hexose ring, and a suitable protocol was established for the selective degradation of carbohydrates with the retention of protein integrity. Using excretory/secretory (ES) proteins, both sodium periodate treated and in their native form, vaccination experiments have shown that sodium periodate treated antigens are as effective as native ES proteins in the generation of both active and passive immunity. This indicates that peptide epitopes alone can induce protective immunity to T. spiralis.", "contents": "An evaluation of the role of carbohydrate epitopes in immunity to Trichinella spiralis. A study is described in which the role of carbohydrate epitopes in the generation of protective immunity to Trichinella spiralis was investigated. Antigen preparations were treated with increasing molar concentrations of sodium periodate, which is known to degrade carbohydrate moieties by cleaving one side of the hexose ring, and a suitable protocol was established for the selective degradation of carbohydrates with the retention of protein integrity. Using excretory/secretory (ES) proteins, both sodium periodate treated and in their native form, vaccination experiments have shown that sodium periodate treated antigens are as effective as native ES proteins in the generation of both active and passive immunity. This indicates that peptide epitopes alone can induce protective immunity to T. spiralis."} {"id": "PMID:1279506", "title": "Development of a bleomycin hamster model of subchronic lung fibrosis.", "content": "The existing bleomycin (BLM)-rodent model of lung fibrosis requires large doses and is often associated with morbidity and high mortality. We have developed an intratracheal multiple-dose BLM-hamster model of lung fibrosis. In this model, 3 consecutive doses of BLM (2.5 U, 2.0 U and 1.5 U/5mL/kg) were instilled intratracheally, one dose per week. The hamsters were killed at 10, 20, 30, 60 and 90 days after the last IT instillation and the lungs were lavaged or perfused with saline. This regimen of BLM administration was devoid of morbidity and caused only 6% overall mortality. Lung prolyl hydroxylase activity at 10 days and hydroxyproline content at 20, 30, 60 and 90 days were significantly higher than noted for the controls. Bronchoalveolar lavage fluid-supernatant protein and the total number of recovered cells of all types were significantly higher than observed for the controls at all times, except at 90 days. Lungs showed a multifocal mixed mononuclear infiltrate at 10 and 20 days and septal fibrosis, which was most severe and organized at 30 days and less severe at 60 and 90 days. The parenchymal lesions were significantly greater than those of the controls at all times, except at 10 days. This model, which required only 6 U BLM/kg, induced a moderate level of lung fibrosis. It has been concluded, therefore, that this model, inasmuch as it is not associated with an overwhelmingly acute inflammation, would be more applicable for screening potential antifibrotic agents than existing models of lung fibrosis.", "contents": "Development of a bleomycin hamster model of subchronic lung fibrosis. The existing bleomycin (BLM)-rodent model of lung fibrosis requires large doses and is often associated with morbidity and high mortality. We have developed an intratracheal multiple-dose BLM-hamster model of lung fibrosis. In this model, 3 consecutive doses of BLM (2.5 U, 2.0 U and 1.5 U/5mL/kg) were instilled intratracheally, one dose per week. The hamsters were killed at 10, 20, 30, 60 and 90 days after the last IT instillation and the lungs were lavaged or perfused with saline. This regimen of BLM administration was devoid of morbidity and caused only 6% overall mortality. Lung prolyl hydroxylase activity at 10 days and hydroxyproline content at 20, 30, 60 and 90 days were significantly higher than noted for the controls. Bronchoalveolar lavage fluid-supernatant protein and the total number of recovered cells of all types were significantly higher than observed for the controls at all times, except at 90 days. Lungs showed a multifocal mixed mononuclear infiltrate at 10 and 20 days and septal fibrosis, which was most severe and organized at 30 days and less severe at 60 and 90 days. The parenchymal lesions were significantly greater than those of the controls at all times, except at 10 days. This model, which required only 6 U BLM/kg, induced a moderate level of lung fibrosis. It has been concluded, therefore, that this model, inasmuch as it is not associated with an overwhelmingly acute inflammation, would be more applicable for screening potential antifibrotic agents than existing models of lung fibrosis."} {"id": "PMID:1279509", "title": "Expression and regulation of L-selectin on eosinophils from human adults and neonates.", "content": "L-Selectin, previously known as LEC.CAM-1, LECAM-1, LAM1, and as the MEL-14, Leu-8, TQ1, and DREG-56 antigens, is a leukocyte membrane protein that participates in adhesion to endothelium. We studied its expression on eosinophils using flow cytometry and the MAb Dreg-56 and Leu-8. Unstimulated peripheral blood eosinophils from healthy adults expressed about one third the level of L-selectin as neutrophils (mean +/- SD specific fluorescence: 20.9 +/- 3.2 versus 54.5 +/- 8.4, p = 0.0001, n = 18). After stimulation with A23187, L-selectin expression on eosinophils was rapidly lost. This was temporally correlated with increased expression of Mac-1 (CD11b/CD18); the kinetics on eosinophils and neutrophils were similar. Eosinophil expression of L-selectin decreased modestly after stimulation with platelet activating factor, but was minimally affected by N-formyl-methionyl-leucyl-phenylalanine, leukotriene B4, or C5a compared with their effects on neutrophils. Eosinophils from cord blood of healthy neonates born at term expressed less L-selectin than adult eosinophils (10.4 +/- 3.8 versus 19.4 +/- 2.7, p = 0.0001, n = 9); the relative reduction was the same as on cord blood neutrophils (36.4 +/- 8.2 versus 55.5 +/- 4.8, p = 0.0001, n = 9). Relative to baseline expression, the responses of neonatal and adult cells to stimulation did not differ. We conclude that neonatal eosinophils have abnormalities in L-selectin expression similar to neonatal neutrophils and suggest that decreased expression of L-selectin and a diminished responsiveness to direct stimulation with chemotactic factors are possible mechanisms that may limit the exudation of eosinophils.", "contents": "Expression and regulation of L-selectin on eosinophils from human adults and neonates. L-Selectin, previously known as LEC.CAM-1, LECAM-1, LAM1, and as the MEL-14, Leu-8, TQ1, and DREG-56 antigens, is a leukocyte membrane protein that participates in adhesion to endothelium. We studied its expression on eosinophils using flow cytometry and the MAb Dreg-56 and Leu-8. Unstimulated peripheral blood eosinophils from healthy adults expressed about one third the level of L-selectin as neutrophils (mean +/- SD specific fluorescence: 20.9 +/- 3.2 versus 54.5 +/- 8.4, p = 0.0001, n = 18). After stimulation with A23187, L-selectin expression on eosinophils was rapidly lost. This was temporally correlated with increased expression of Mac-1 (CD11b/CD18); the kinetics on eosinophils and neutrophils were similar. Eosinophil expression of L-selectin decreased modestly after stimulation with platelet activating factor, but was minimally affected by N-formyl-methionyl-leucyl-phenylalanine, leukotriene B4, or C5a compared with their effects on neutrophils. Eosinophils from cord blood of healthy neonates born at term expressed less L-selectin than adult eosinophils (10.4 +/- 3.8 versus 19.4 +/- 2.7, p = 0.0001, n = 9); the relative reduction was the same as on cord blood neutrophils (36.4 +/- 8.2 versus 55.5 +/- 4.8, p = 0.0001, n = 9). Relative to baseline expression, the responses of neonatal and adult cells to stimulation did not differ. We conclude that neonatal eosinophils have abnormalities in L-selectin expression similar to neonatal neutrophils and suggest that decreased expression of L-selectin and a diminished responsiveness to direct stimulation with chemotactic factors are possible mechanisms that may limit the exudation of eosinophils."} {"id": "PMID:1279507", "title": "[Spheroidal deposits of amyloid in prolactin-secreting pituitary adenomas].", "content": "Nine peculiar cases of pituitary adenomas were pointed out by a retrospective investigation at the Ospedale di Legnano (from 1978 to 1984) and at the Ospedale di Circolo di Varese (from 1973 to 1986). These tumours are chromophobe adenomas with diffuse structure. Histologically they show typical, large, spheroid and concentric amyloid deposits, in addition to common, amorphous--often perivascular--ones. They were investigated by histochemical methods (Crystal-Violet, Congo-Red) and by immunohistochemical ones as well (anti-PRL and anti-GH), showing that these deposits are amyloid and are in close relation with PRL production. In particular, by immunohistochemical methods we found out that the cells of the tumours displaying spheroidal bodies do contain prolactin, not GH. The amyloid deposits are also immunohistochemically positive to anti-PRL serum, not to anti-GH serum. Finally, by considering the information present in literature, we have discussed the possible pathogenic mechanisms leading to amyloid deposits in pituitary adenomas.", "contents": "[Spheroidal deposits of amyloid in prolactin-secreting pituitary adenomas]. Nine peculiar cases of pituitary adenomas were pointed out by a retrospective investigation at the Ospedale di Legnano (from 1978 to 1984) and at the Ospedale di Circolo di Varese (from 1973 to 1986). These tumours are chromophobe adenomas with diffuse structure. Histologically they show typical, large, spheroid and concentric amyloid deposits, in addition to common, amorphous--often perivascular--ones. They were investigated by histochemical methods (Crystal-Violet, Congo-Red) and by immunohistochemical ones as well (anti-PRL and anti-GH), showing that these deposits are amyloid and are in close relation with PRL production. In particular, by immunohistochemical methods we found out that the cells of the tumours displaying spheroidal bodies do contain prolactin, not GH. The amyloid deposits are also immunohistochemically positive to anti-PRL serum, not to anti-GH serum. Finally, by considering the information present in literature, we have discussed the possible pathogenic mechanisms leading to amyloid deposits in pituitary adenomas."} {"id": "PMID:1279510", "title": "Quinolinate in brain and cerebrospinal fluid in rat models of congenital hyperammonemia.", "content": "Children with inborn errors of urea synthesis who survive neonatal hyperammonemic coma commonly exhibit cognitive deficits and neurologic abnormalities. Yet, there is evidence that ammonia is not the only neurotoxin. Hyperammonemia appears to induce a number of neurochemical alterations. In rodent models of hyperammonemia, uptake of L-tryptophan into brain is increased. It has been reported that in an experimental rat model of hepatic encephalopathy, in the ammonium acetate-injected rat, and in patients with hepatic failure and inborn errors of ammonia metabolism, quinolinate, a tryptophan metabolite, is increased. Elevations in quinolinate are of particular concern, as quinolinate could excessively activate the N-methyl-D-aspartate subclass of excitatory amino acid receptors, thereby causing selective neuronal necrosis. We sought to identify an animal model that would replicate the increases in quinolinate that have been associated with hyperammonemia in humans. Levels of quinolinate were measured in hyperammonemic urease-infused rats and ammonium acetate-injected rats. In the urease-infused rat, brain tryptophan was doubled, and serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly increased. Yet, despite the increase in tryptophan and evidence for increased metabolism of tryptophan to serotonin, there were no observed increases of quinolinate in brain, cerebrospinal fluid, or plasma. In the ammonium acetate-injected rat, significant increases of 5-hydroxyindoleacetic acid in cerebral cortex were also observed, but quinolinate did not change in cerebrospinal fluid or cerebral cortex. In summary, we were unable to demonstrate an increase of quinolinate in brain or cerebrospinal fluid in these rat models of hyperammonemia.", "contents": "Quinolinate in brain and cerebrospinal fluid in rat models of congenital hyperammonemia. Children with inborn errors of urea synthesis who survive neonatal hyperammonemic coma commonly exhibit cognitive deficits and neurologic abnormalities. Yet, there is evidence that ammonia is not the only neurotoxin. Hyperammonemia appears to induce a number of neurochemical alterations. In rodent models of hyperammonemia, uptake of L-tryptophan into brain is increased. It has been reported that in an experimental rat model of hepatic encephalopathy, in the ammonium acetate-injected rat, and in patients with hepatic failure and inborn errors of ammonia metabolism, quinolinate, a tryptophan metabolite, is increased. Elevations in quinolinate are of particular concern, as quinolinate could excessively activate the N-methyl-D-aspartate subclass of excitatory amino acid receptors, thereby causing selective neuronal necrosis. We sought to identify an animal model that would replicate the increases in quinolinate that have been associated with hyperammonemia in humans. Levels of quinolinate were measured in hyperammonemic urease-infused rats and ammonium acetate-injected rats. In the urease-infused rat, brain tryptophan was doubled, and serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly increased. Yet, despite the increase in tryptophan and evidence for increased metabolism of tryptophan to serotonin, there were no observed increases of quinolinate in brain, cerebrospinal fluid, or plasma. In the ammonium acetate-injected rat, significant increases of 5-hydroxyindoleacetic acid in cerebral cortex were also observed, but quinolinate did not change in cerebrospinal fluid or cerebral cortex. In summary, we were unable to demonstrate an increase of quinolinate in brain or cerebrospinal fluid in these rat models of hyperammonemia."} {"id": "PMID:1279508", "title": "[Laboratory diagnosis of Pneumocystis carinii: comparison of cytological, immunofluorescent and immunocytochemical staining].", "content": "Authors review several methods for diagnosis of Pneumocystis carinii on BAL fluid in AIDS patients aiming to identify ideal routine technic. Giemsa, Gomori and Toluidine Blue staining. Direct and Indirect Immunofluorescence. Immunocytochemical methods were tested and advantages/disadvantages compared on BAL fluid from AIDS patients. Pneumocystis carinii was detected in 7 out 21 cases (33%). Gomori staining and Toluidine Blue staining were chosen for routine Pneumocystis carinii detection while IF technics are deserved as very useful in fields showing high fungal ++ contamination (inducted sputum).", "contents": "[Laboratory diagnosis of Pneumocystis carinii: comparison of cytological, immunofluorescent and immunocytochemical staining]. Authors review several methods for diagnosis of Pneumocystis carinii on BAL fluid in AIDS patients aiming to identify ideal routine technic. Giemsa, Gomori and Toluidine Blue staining. Direct and Indirect Immunofluorescence. Immunocytochemical methods were tested and advantages/disadvantages compared on BAL fluid from AIDS patients. Pneumocystis carinii was detected in 7 out 21 cases (33%). Gomori staining and Toluidine Blue staining were chosen for routine Pneumocystis carinii detection while IF technics are deserved as very useful in fields showing high fungal ++ contamination (inducted sputum)."} {"id": "PMID:1279513", "title": "Serum bilirubin levels, intracranial hemorrhage, and the risk of developmental problems in very low birth weight neonates.", "content": "To study whether elevated levels of bilirubin in the neonatal period increase the risk of developmental problems for very low birth weight neonates, the investigators used data from a geographically based sample of 495 very low birth weight neonates, born January 1, 1985, to December 31, 1989, who survived to 1 year of adjusted age. Maximum neonatal bilirubin levels were found in medical records. A developmental problem was defined as either cerebral palsy or a Bayley Mental Developmental Index of less than 68 at 1 year adjusted age. Potentially confounding factors were controlled using logistic regression. To control for the effects of intracranial abnormalities (eg, intraventricular hemorrhage), separate logistic regression analyses were carried out for three strata, defined according to the results of cranial ultrasonography. In these analyses, the following odds ratios (with 95% confidence limits) were found for the association of maximum neonatal bilirubin concentration and developmental problems: for subjects without intracranial abnormalities, 0.9 (0.7, 1.9); for subjects with uncomplicated intracranial hemorrhage, 1.5 (0.8, 2.5); for subjects with complicated intracranial hemorrhage or intraparenchymal echo-densities, 1.2 (0.4, 3.6). In summary, in analyses controlled for confounding factors, maximum neonatal bilirubin level was not consistently associated with the risk of developmental problems identifiable at 1 year.", "contents": "Serum bilirubin levels, intracranial hemorrhage, and the risk of developmental problems in very low birth weight neonates. To study whether elevated levels of bilirubin in the neonatal period increase the risk of developmental problems for very low birth weight neonates, the investigators used data from a geographically based sample of 495 very low birth weight neonates, born January 1, 1985, to December 31, 1989, who survived to 1 year of adjusted age. Maximum neonatal bilirubin levels were found in medical records. A developmental problem was defined as either cerebral palsy or a Bayley Mental Developmental Index of less than 68 at 1 year adjusted age. Potentially confounding factors were controlled using logistic regression. To control for the effects of intracranial abnormalities (eg, intraventricular hemorrhage), separate logistic regression analyses were carried out for three strata, defined according to the results of cranial ultrasonography. In these analyses, the following odds ratios (with 95% confidence limits) were found for the association of maximum neonatal bilirubin concentration and developmental problems: for subjects without intracranial abnormalities, 0.9 (0.7, 1.9); for subjects with uncomplicated intracranial hemorrhage, 1.5 (0.8, 2.5); for subjects with complicated intracranial hemorrhage or intraparenchymal echo-densities, 1.2 (0.4, 3.6). In summary, in analyses controlled for confounding factors, maximum neonatal bilirubin level was not consistently associated with the risk of developmental problems identifiable at 1 year."} {"id": "PMID:1279514", "title": "Activation of basolateral Cl- channels in the rat colonic epithelium during regulatory volume decrease.", "content": "Exposure to a hypotonic medium caused an increase in the diameter of isolated crypts from the rat colon. The increase in cell volume was only transient and lasted about 7 min. Despite of the continuous presence of the hypotonic medium, cell volume decreased again. This regulatory volume decrease (RVD) was inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a Cl- channel blocker, and by Ba2+, a K+ channel blocker. Cell-attached patch-clamp recordings revealed that the RVD was associated with the activation of previously silent basolateral channels. These channels were identified after excision of the patch as Cl- channels (28 pS) and as K+ channels (45-60 pS). The RVD was dependent on the presence of external Ca2+. The phospholipase A2 inhibitor, quinacrine, and the lipoxygenase blocker, nordihydroguaiaretic acid, inhibited RVD, while indomethacin had no effect. In Ussing chamber experiments an exposure to hypotonic media caused an initial, transient increase in tissue conductance (Gt), followed by a prolonged decrease in short-circuit current (Isc) and the potential difference (V). The height of the electrical response was dependent on the decrease in the osmolarity in a range from 20 mosmol l-1 to 90 mosmol l-1. The increase in Gt was blocked by NPPB and Ba2+, whereas the decrease in Isc or V was inhibited by NPPB but enhanced by Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Activation of basolateral Cl- channels in the rat colonic epithelium during regulatory volume decrease. Exposure to a hypotonic medium caused an increase in the diameter of isolated crypts from the rat colon. The increase in cell volume was only transient and lasted about 7 min. Despite of the continuous presence of the hypotonic medium, cell volume decreased again. This regulatory volume decrease (RVD) was inhibited by 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB), a Cl- channel blocker, and by Ba2+, a K+ channel blocker. Cell-attached patch-clamp recordings revealed that the RVD was associated with the activation of previously silent basolateral channels. These channels were identified after excision of the patch as Cl- channels (28 pS) and as K+ channels (45-60 pS). The RVD was dependent on the presence of external Ca2+. The phospholipase A2 inhibitor, quinacrine, and the lipoxygenase blocker, nordihydroguaiaretic acid, inhibited RVD, while indomethacin had no effect. In Ussing chamber experiments an exposure to hypotonic media caused an initial, transient increase in tissue conductance (Gt), followed by a prolonged decrease in short-circuit current (Isc) and the potential difference (V). The height of the electrical response was dependent on the decrease in the osmolarity in a range from 20 mosmol l-1 to 90 mosmol l-1. The increase in Gt was blocked by NPPB and Ba2+, whereas the decrease in Isc or V was inhibited by NPPB but enhanced by Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279515", "title": "Chloride channels in cultured human skeletal muscle are regulated by G proteins.", "content": "The regulation of Cl- channels in human myoballs by G proteins was studied using whole-cell and inside-out patch recordings. After perfusion of the cell with 0.1 mM GTP[gamma S], the specific Cl- conductance, GCl, at standard resting potential (-85 mV) was increased from 5.9 microS/cm2 to 103 microS/cm2, and the kinetics upon stepping the potential to positive values was changed from an activating current with very slow inactivation to a fast inactivating current with no potential-dependent activation. These effects were not affected by the simultaneous blockade of several signal cascades involving G proteins. Addition of the protein kinase blockers PKI (25 microM), H8 (10 microM), or of the phospholipase-A2-blocking agent quinacrine (10 microM), had not much influence on these GTP[gamma S] effects. Buffering of the intracellular Ca2+ concentration (0.1 microM) or addition of the Ca2+/calmodulin antagonist trifluoperazine (50 microM) was also without effect. Pre-incubation of the cells with pertussis toxin or with cholera toxin did not change GCl. In excised inside-out patches voltage-clamped at -85 mV, application of GTP[gamma S] influenced the \"intermediate\" Cl- channel, the Cl- channel type having the highest density in these cells, by increasing the number of transitions in a half-conductance state. The probability of the channel being in one of the two conducting states rose from 0.015 to 0.67, and the kinetics of the single-channel currents was changed so that, on average, it was similar to the whole-cell current kinetics seen after application of GTP[gamma S]. It is concluded that a G protein is directly interacting with these channels.", "contents": "Chloride channels in cultured human skeletal muscle are regulated by G proteins. The regulation of Cl- channels in human myoballs by G proteins was studied using whole-cell and inside-out patch recordings. After perfusion of the cell with 0.1 mM GTP[gamma S], the specific Cl- conductance, GCl, at standard resting potential (-85 mV) was increased from 5.9 microS/cm2 to 103 microS/cm2, and the kinetics upon stepping the potential to positive values was changed from an activating current with very slow inactivation to a fast inactivating current with no potential-dependent activation. These effects were not affected by the simultaneous blockade of several signal cascades involving G proteins. Addition of the protein kinase blockers PKI (25 microM), H8 (10 microM), or of the phospholipase-A2-blocking agent quinacrine (10 microM), had not much influence on these GTP[gamma S] effects. Buffering of the intracellular Ca2+ concentration (0.1 microM) or addition of the Ca2+/calmodulin antagonist trifluoperazine (50 microM) was also without effect. Pre-incubation of the cells with pertussis toxin or with cholera toxin did not change GCl. In excised inside-out patches voltage-clamped at -85 mV, application of GTP[gamma S] influenced the \"intermediate\" Cl- channel, the Cl- channel type having the highest density in these cells, by increasing the number of transitions in a half-conductance state. The probability of the channel being in one of the two conducting states rose from 0.015 to 0.67, and the kinetics of the single-channel currents was changed so that, on average, it was similar to the whole-cell current kinetics seen after application of GTP[gamma S]. It is concluded that a G protein is directly interacting with these channels."} {"id": "PMID:1279516", "title": "Pressure-clamp: a method for rapid step perturbation of mechanosensitive channels.", "content": "Here we describe a pressure-clamp method for applying suction or pressure steps to membrane patches in order to study the activation, adaptation and relaxation characteristics of mechanosensitive (MS) channels. A description is given of the mechanical arrangement of the pressure clamp which involves a balance between negative (suction) and positive pressures. The electronic circuitry of the feedback control is described. We also describe the optimal time response (approximately 10 ms) of the pressure-clamp, the amplitude of pressure resolution (0.2-0.5 mmHg; 27-67 Pa) and the factors influencing these parameters. We illustrate the applications of the clamp on the Xenopus oocyte and cultured skeletal myotubes from dystrophic mouse (mdx) muscle, both of which express MS channels. Studies with pressure/suction pulses indicate that in both muscles and oocytes MS channel activity displays adaptation. The ability to study current relaxations following step changes in pressure/suction using the pressure-clamp in combination with patch-clamp techniques provides the opportunity for analysis of the time, voltage and pressure dependence of the opening and closing of MS channels.", "contents": "Pressure-clamp: a method for rapid step perturbation of mechanosensitive channels. Here we describe a pressure-clamp method for applying suction or pressure steps to membrane patches in order to study the activation, adaptation and relaxation characteristics of mechanosensitive (MS) channels. A description is given of the mechanical arrangement of the pressure clamp which involves a balance between negative (suction) and positive pressures. The electronic circuitry of the feedback control is described. We also describe the optimal time response (approximately 10 ms) of the pressure-clamp, the amplitude of pressure resolution (0.2-0.5 mmHg; 27-67 Pa) and the factors influencing these parameters. We illustrate the applications of the clamp on the Xenopus oocyte and cultured skeletal myotubes from dystrophic mouse (mdx) muscle, both of which express MS channels. Studies with pressure/suction pulses indicate that in both muscles and oocytes MS channel activity displays adaptation. The ability to study current relaxations following step changes in pressure/suction using the pressure-clamp in combination with patch-clamp techniques provides the opportunity for analysis of the time, voltage and pressure dependence of the opening and closing of MS channels."} {"id": "PMID:1279517", "title": "Does the gradual hydroosmotic response to antidiuretic hormone depend on intracellular cAMP accumulation or on the formation of intramembrane particle aggregates?", "content": "In experiments on frog urinary bladder the mechanisms behind the gradual development of a hydroosmotic reaction to antidiuretic hormone (ADH) were investigated. It was suggested that the velocity of hydroosmotic reaction may be limited by (a) formation and insertion of particle aggregates into the apical membrane or (b) by velocity of cAMP formation. The urinary bladders were exposed to 23 nM ADH for different times (from 1 to 20 min) and water flow was measured over a period of 40 min. It was found that the value of the full hydroosmotic response increased progressively with the time of exposure to the hormone; however, the enhancement of water flow was equal during each time interval before reaching the reaction maximum. A direct correlation between the value of ADH-stimulated water flow, cAMP content in bladder tissue and frequency of particle aggregates in the granular cell apical membrane was observed. The content of cAMP in ADH-treated bladders was higher by 80% in the absence than in the presence of an osmotic gradient. Pretreatment of urinary bladders with 50 microM cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, significantly accelerated the development of the hydroosmotic reaction and increased the magnitude of water flow in comparison with the effect of ADH only. No changes in cyclic AMP phosphodiesterase activity were found in the urinary bladder homogenates under the action of ADH, so it seems likely that accumulation of cAMP depends only on the increase of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Does the gradual hydroosmotic response to antidiuretic hormone depend on intracellular cAMP accumulation or on the formation of intramembrane particle aggregates? In experiments on frog urinary bladder the mechanisms behind the gradual development of a hydroosmotic reaction to antidiuretic hormone (ADH) were investigated. It was suggested that the velocity of hydroosmotic reaction may be limited by (a) formation and insertion of particle aggregates into the apical membrane or (b) by velocity of cAMP formation. The urinary bladders were exposed to 23 nM ADH for different times (from 1 to 20 min) and water flow was measured over a period of 40 min. It was found that the value of the full hydroosmotic response increased progressively with the time of exposure to the hormone; however, the enhancement of water flow was equal during each time interval before reaching the reaction maximum. A direct correlation between the value of ADH-stimulated water flow, cAMP content in bladder tissue and frequency of particle aggregates in the granular cell apical membrane was observed. The content of cAMP in ADH-treated bladders was higher by 80% in the absence than in the presence of an osmotic gradient. Pretreatment of urinary bladders with 50 microM cyclic nucleotide phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, significantly accelerated the development of the hydroosmotic reaction and increased the magnitude of water flow in comparison with the effect of ADH only. No changes in cyclic AMP phosphodiesterase activity were found in the urinary bladder homogenates under the action of ADH, so it seems likely that accumulation of cAMP depends only on the increase of adenylate cyclase activity.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279518", "title": "Effect of thapsigargin and caffeine on Ca2+ homeostasis in HeLa cells: implications for histamine-induced Ca2+ oscillations.", "content": "Several studies have already established that the stimulation of H1 receptors by exogenous histamine induces intracellular Ca2+ oscillations in HeLa cells. The molecular mechanism underlying this oscillatory process remains, however, unclear. A series of fura-2 experiments was undertaken in which the nature of the Ca2+ pools involved in the histamine-induced Ca2+ oscillations was investigated using the tumour promoter agent thapsigargin (TG) and the Ca(2+)-induced Ca(2+)-release promoter, caffeine. The results obtained indicate first that TG causes a gradual increase in cytosolic Ca2+ without inducing internal Ca2+ oscillations, and second that TG and histamine share common internal Ca2+ storage sites. The latter conclusion was derived from experiments performed in the absence of external Ca2+, where the addition of TG before histamine resulted in a total inhibition of the Ca2+ response linked to H1 receptor stimulation, whereas the addition of histamine before TG decreased by more than 90% the TG-induced Ca2+ release. Finally; TG was found to inhibit irreversibly histamine-induced Ca2+ oscillations when added to the bathing medium during the oscillatory process. The effect of caffeine at concentrations ranging from 1 mM to 10 mM on intracellular Ca2+ homeostasis was also investigated. The results obtained show that caffeine does not affect systematically the internal Ca2+ concentration in resting and TG-stimulated HeLa cells, but increases the Ca2+ sequestration ability of inositol-trisphosphate (InsP3)-related Ca2+ stores.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effect of thapsigargin and caffeine on Ca2+ homeostasis in HeLa cells: implications for histamine-induced Ca2+ oscillations. Several studies have already established that the stimulation of H1 receptors by exogenous histamine induces intracellular Ca2+ oscillations in HeLa cells. The molecular mechanism underlying this oscillatory process remains, however, unclear. A series of fura-2 experiments was undertaken in which the nature of the Ca2+ pools involved in the histamine-induced Ca2+ oscillations was investigated using the tumour promoter agent thapsigargin (TG) and the Ca(2+)-induced Ca(2+)-release promoter, caffeine. The results obtained indicate first that TG causes a gradual increase in cytosolic Ca2+ without inducing internal Ca2+ oscillations, and second that TG and histamine share common internal Ca2+ storage sites. The latter conclusion was derived from experiments performed in the absence of external Ca2+, where the addition of TG before histamine resulted in a total inhibition of the Ca2+ response linked to H1 receptor stimulation, whereas the addition of histamine before TG decreased by more than 90% the TG-induced Ca2+ release. Finally; TG was found to inhibit irreversibly histamine-induced Ca2+ oscillations when added to the bathing medium during the oscillatory process. The effect of caffeine at concentrations ranging from 1 mM to 10 mM on intracellular Ca2+ homeostasis was also investigated. The results obtained show that caffeine does not affect systematically the internal Ca2+ concentration in resting and TG-stimulated HeLa cells, but increases the Ca2+ sequestration ability of inositol-trisphosphate (InsP3)-related Ca2+ stores.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279519", "title": "Group I permuted intron-exon (PIE) sequences self-splice to produce circular exons.", "content": "Circularly permuted group I intron precursor RNAs, containing end-to-end fused exons which interrupt half-intron sequences, were generated and tested for self-splicing activity. An autocatalytic RNA can form when the primary order of essential intron sequence elements, splice sites, and exons are permuted in this manner. Covalent attachment of guanosine to the 5' half-intron product, and accurate exon ligation indicated that the mechanism and specificity of splicing were not altered. However, because the exons were fused and the order of the splice sites reversed, splicing released the fused-exon as a circle. With this arrangement of splice sites, circular exon production was a prediction of the group I splicing mechanism. Circular RNAs have properties that would make them attractive for certain studies of RNA structure and function. Reversal of splice site sequences in a context that allows splicing, such as those generated by circularly permuted group I introns, could be used to generate short defined sequences of circular RNA in vitro and perhaps in vivo.", "contents": "Group I permuted intron-exon (PIE) sequences self-splice to produce circular exons. Circularly permuted group I intron precursor RNAs, containing end-to-end fused exons which interrupt half-intron sequences, were generated and tested for self-splicing activity. An autocatalytic RNA can form when the primary order of essential intron sequence elements, splice sites, and exons are permuted in this manner. Covalent attachment of guanosine to the 5' half-intron product, and accurate exon ligation indicated that the mechanism and specificity of splicing were not altered. However, because the exons were fused and the order of the splice sites reversed, splicing released the fused-exon as a circle. With this arrangement of splice sites, circular exon production was a prediction of the group I splicing mechanism. Circular RNAs have properties that would make them attractive for certain studies of RNA structure and function. Reversal of splice site sequences in a context that allows splicing, such as those generated by circularly permuted group I introns, could be used to generate short defined sequences of circular RNA in vitro and perhaps in vivo."} {"id": "PMID:1279520", "title": "Elements of an archaeal promoter defined by mutational analysis.", "content": "The sequence requirements for specific and efficient transcription from the 16S/23S rRNA promoter of Sulfolobus shibatae were analysed by point mutations and by cassette mutations using an in vitro transcription system. The examination of the box A-containing distal promoter element (DPE) showed the great importance of the TA sequence in the center of box A for transcription efficiency and the influence of the sequence upstream of box A on determining the distance between the DPE and the start site. In most positions of box A, replacement of the wild type bases by adenines or thymines are less detrimental than replacements by cytosines or guanines. The effectiveness of the proximal promoter element (PPE) was not merely determined by its high A + T content but appeared to be directly related to its nucleotide sequence. At the start site a pyrimidine/purine (py/pu) sequence was necessary for unambiguous initiation as shown by analysis of mutants where the wild type start base was replaced. The sequence of box A optimal for promoter function in vitro is identical to the consensus of 84 mapped archaeal promoter sequences.", "contents": "Elements of an archaeal promoter defined by mutational analysis. The sequence requirements for specific and efficient transcription from the 16S/23S rRNA promoter of Sulfolobus shibatae were analysed by point mutations and by cassette mutations using an in vitro transcription system. The examination of the box A-containing distal promoter element (DPE) showed the great importance of the TA sequence in the center of box A for transcription efficiency and the influence of the sequence upstream of box A on determining the distance between the DPE and the start site. In most positions of box A, replacement of the wild type bases by adenines or thymines are less detrimental than replacements by cytosines or guanines. The effectiveness of the proximal promoter element (PPE) was not merely determined by its high A + T content but appeared to be directly related to its nucleotide sequence. At the start site a pyrimidine/purine (py/pu) sequence was necessary for unambiguous initiation as shown by analysis of mutants where the wild type start base was replaced. The sequence of box A optimal for promoter function in vitro is identical to the consensus of 84 mapped archaeal promoter sequences."} {"id": "PMID:1279521", "title": "Temperature-dependent template switching during in vitro cDNA synthesis by the AMV-reverse transcriptase.", "content": "Reverse transcriptase template switching has been invoked to explain several aspects of retroviral replication and recombination, and has been reported in vitro for the Moloney murine leukemia virus (M-MuLV) reverse transcriptase. During in vitro cDNA synthesis, the avian myeloblastosis virus (AMV) reverse transcriptase can switch from one template to another in a homology-dependent and temperature-dependent manner. Chimeric cDNA molecules are generated within 30 min at high incubation temperatures, with an increasing efficiency from 42 degrees C to 50 degrees C. Such products are detectable only after much longer incubation times when primer extension reactions are carried out at lower temperatures (90 min at 37 degrees C).", "contents": "Temperature-dependent template switching during in vitro cDNA synthesis by the AMV-reverse transcriptase. Reverse transcriptase template switching has been invoked to explain several aspects of retroviral replication and recombination, and has been reported in vitro for the Moloney murine leukemia virus (M-MuLV) reverse transcriptase. During in vitro cDNA synthesis, the avian myeloblastosis virus (AMV) reverse transcriptase can switch from one template to another in a homology-dependent and temperature-dependent manner. Chimeric cDNA molecules are generated within 30 min at high incubation temperatures, with an increasing efficiency from 42 degrees C to 50 degrees C. Such products are detectable only after much longer incubation times when primer extension reactions are carried out at lower temperatures (90 min at 37 degrees C)."} {"id": "PMID:1279526", "title": "Subxiphoid approach for implantable cardioverter defibrillator in patients with previous coronary bypass surgery.", "content": "From February 1988 until August 1991, 28 patients with prior coronary artery bypass grafting (CABG) received implantable cardioverter defibrillator (ICD) therapy via a subxiphoid approach. Only one patient required conversion to a median sternotomy incision. The mean defibrillation threshold was 11.9 +/- 4.4 J. The mean R wave was 8.2 +/- 3.7 mV. One perioperative death occurred due to heart failure (mortality rate 1/28 [3.50%]). No patient required reexploration for bleeding. The subxiphoid method for ICD electrode implantation is safe and reliable in patients with prior CABG surgery.", "contents": "Subxiphoid approach for implantable cardioverter defibrillator in patients with previous coronary bypass surgery. From February 1988 until August 1991, 28 patients with prior coronary artery bypass grafting (CABG) received implantable cardioverter defibrillator (ICD) therapy via a subxiphoid approach. Only one patient required conversion to a median sternotomy incision. The mean defibrillation threshold was 11.9 +/- 4.4 J. The mean R wave was 8.2 +/- 3.7 mV. One perioperative death occurred due to heart failure (mortality rate 1/28 [3.50%]). No patient required reexploration for bleeding. The subxiphoid method for ICD electrode implantation is safe and reliable in patients with prior CABG surgery."} {"id": "PMID:1279527", "title": "A Soviet nuclear pacemaker.", "content": "A Soviet nuclear pacemaker is described. It is a large VOO bipolar pacemaker, probably nonprogrammable. It has unique electrode connectors. No isotope leak or excessive radiation hazard was detected. Because we had no knowledge of its end-of-life markers and because of the impossibility of assuming long-term safety, the device was removed.", "contents": "A Soviet nuclear pacemaker. A Soviet nuclear pacemaker is described. It is a large VOO bipolar pacemaker, probably nonprogrammable. It has unique electrode connectors. No isotope leak or excessive radiation hazard was detected. Because we had no knowledge of its end-of-life markers and because of the impossibility of assuming long-term safety, the device was removed."} {"id": "PMID:1279528", "title": "Suppression of incessant ventricular tachycardia in hypertrophic cardiomyopathy associated with improvement of severe left ventricular dysfunction.", "content": "A 32-year-old black man presented with a history of palpitations since childhood and two syncopal episodes. He was found to have incessant ventricular tachycardia, impaired left ventricular contraction (ejection fraction 9%), and nonobstructive hypertrophic cardiomyopathy. Procainamide abolished the arrhythmia and the ejection fraction rose to 22% in sinus rhythm. Later treatment was switched to amiodarone, which suppressed the ventricular tachycardia but necessitated pacemaker implantation. He has remained well during the subsequent 2 years. Left ventricular ejection fraction has increased to 47% measured in paced rhythm. The improvement in left ventricular function has been attributed to suppression of the incessant ventricular tachycardia.", "contents": "Suppression of incessant ventricular tachycardia in hypertrophic cardiomyopathy associated with improvement of severe left ventricular dysfunction. A 32-year-old black man presented with a history of palpitations since childhood and two syncopal episodes. He was found to have incessant ventricular tachycardia, impaired left ventricular contraction (ejection fraction 9%), and nonobstructive hypertrophic cardiomyopathy. Procainamide abolished the arrhythmia and the ejection fraction rose to 22% in sinus rhythm. Later treatment was switched to amiodarone, which suppressed the ventricular tachycardia but necessitated pacemaker implantation. He has remained well during the subsequent 2 years. Left ventricular ejection fraction has increased to 47% measured in paced rhythm. The improvement in left ventricular function has been attributed to suppression of the incessant ventricular tachycardia."} {"id": "PMID:1279529", "title": "Modification of late potentials by intracoronary ethanol infusion.", "content": "Antiarrhythmic drugs have no consistent effects on the signal-averaged electrocardiogram (ECG) while successful surgical ablation of ventricular tachycardia is known to abolish late potentials. Ten patients with prior myocardial infarction had successful ablation of recurrent sustained ventricular tachycardia by selective ethanol infusion into a small coronary vessel supplying the tachycardia origin. Signal-averaged ECGs were performed before and after initially successful ablation in patients without pacemaker dependence or intraventricular conduction delay to assess the effects on late potentials and to determine if the signal-averaged ECG could predict ventricular tachycardia recurrence. Only four of ten patients were eligible for study and all four had late potentials prior to ethanol ablation. Late potentials were abolished in one patient who has not had an arrhythmia recurrence in 25 months. One patient with sudden death and another patient with ventricular tachycardia recurrence had persistent late potentials post procedure that were modified by a reduction in terminal voltage and lengthening of terminal low amplitude signal. The fourth patient who receives chronic amiodarone had no arrhythmia recurrence in spite of persistent but modified late potentials. Thus, the abolition of late potentials after ethanol ablation may predict freedom from arrhythmia recurrence.", "contents": "Modification of late potentials by intracoronary ethanol infusion. Antiarrhythmic drugs have no consistent effects on the signal-averaged electrocardiogram (ECG) while successful surgical ablation of ventricular tachycardia is known to abolish late potentials. Ten patients with prior myocardial infarction had successful ablation of recurrent sustained ventricular tachycardia by selective ethanol infusion into a small coronary vessel supplying the tachycardia origin. Signal-averaged ECGs were performed before and after initially successful ablation in patients without pacemaker dependence or intraventricular conduction delay to assess the effects on late potentials and to determine if the signal-averaged ECG could predict ventricular tachycardia recurrence. Only four of ten patients were eligible for study and all four had late potentials prior to ethanol ablation. Late potentials were abolished in one patient who has not had an arrhythmia recurrence in 25 months. One patient with sudden death and another patient with ventricular tachycardia recurrence had persistent late potentials post procedure that were modified by a reduction in terminal voltage and lengthening of terminal low amplitude signal. The fourth patient who receives chronic amiodarone had no arrhythmia recurrence in spite of persistent but modified late potentials. Thus, the abolition of late potentials after ethanol ablation may predict freedom from arrhythmia recurrence."} {"id": "PMID:1279530", "title": "Apparent P wave undersensing in a DDD pacemaker post exercise.", "content": "Wenckebach behavior of DDD pacemakers occurring when the P-P interval varies between the programmed upper rate interval and the total atrial refractory period is symmetrical in a sense that the pacemaker response during atrial rate acceleration is similar to the pacemaker response during atrial rate deceleration. This phenomenon can be observed in all patients with persistent AV block in whom a DDD pacemaker is implanted, during exercise testing when the spontaneous atrial rate exceeds the selected upper rate, i.e., the programmed upper rate interval. However, this phenomenon will not be observed in all patients with intermittent intact AV conduction during exercise. In this case report we describe a patient who showed an asymmetrical response during a bicycle exercise test. There was 1:1 atrial sensing ventricular pacing until the atrial rate exceeded the upper rate of 140 ppm, while atrial sensing was restored during recovery when the conducted sinus rhythm had decreased to 105 beats/min.", "contents": "Apparent P wave undersensing in a DDD pacemaker post exercise. Wenckebach behavior of DDD pacemakers occurring when the P-P interval varies between the programmed upper rate interval and the total atrial refractory period is symmetrical in a sense that the pacemaker response during atrial rate acceleration is similar to the pacemaker response during atrial rate deceleration. This phenomenon can be observed in all patients with persistent AV block in whom a DDD pacemaker is implanted, during exercise testing when the spontaneous atrial rate exceeds the selected upper rate, i.e., the programmed upper rate interval. However, this phenomenon will not be observed in all patients with intermittent intact AV conduction during exercise. In this case report we describe a patient who showed an asymmetrical response during a bicycle exercise test. There was 1:1 atrial sensing ventricular pacing until the atrial rate exceeded the upper rate of 140 ppm, while atrial sensing was restored during recovery when the conducted sinus rhythm had decreased to 105 beats/min."} {"id": "PMID:1279531", "title": "Radiofrequency catheter ablation of the AV node to improve the function of an antitachycardia implantable defibrillator.", "content": "A case of coexisting atrial fibrillation and ventricular tachycardia in a patient with an implantable cardioverter defibrillator is described. Despite careful reprogramming, the device was not always able to distinguish between the two arrhythmias and continued to deliver inappropriate antitachycardia therapy including DC shocks. Attempts to pharmacologically control the atrial fibrillation were unsuccessful so radiofrequency ablation of the atrioventricular node was performed. Following successful ablation, there have been no further false detections no episodes of further ventricular tachycardia.", "contents": "Radiofrequency catheter ablation of the AV node to improve the function of an antitachycardia implantable defibrillator. A case of coexisting atrial fibrillation and ventricular tachycardia in a patient with an implantable cardioverter defibrillator is described. Despite careful reprogramming, the device was not always able to distinguish between the two arrhythmias and continued to deliver inappropriate antitachycardia therapy including DC shocks. Attempts to pharmacologically control the atrial fibrillation were unsuccessful so radiofrequency ablation of the atrioventricular node was performed. Following successful ablation, there have been no further false detections no episodes of further ventricular tachycardia."} {"id": "PMID:1279532", "title": "Differentiation between monomorphic ventricular tachycardia and sinus tachycardia based on the right ventricular evoked potential.", "content": "The differentiation between ventricular tachycardia (VT) and sinus tachycardia (ST) is problematic in some patients with implantable defibrillators and/or antitachycardia pacemakers. The integral of the ventricular endocardial evoked response, or paced depolarization integral (PDI), has been demonstrated to undergo characteristic changes with a variety of stimuli including catecholamines, pacing rate, and exercise. We hypothesized that the PDI recorded from a unipolar transvenous right ventricular endocardial catheter would differentiate VT from ST. The PDI was calculated from a unipolar pacing stimulus, delivered via a cathode in the right ventricular apex, and the reference electrode, a quadripolar catheter positioned in the superior vena cava. PDIs were measured in 22 patients during VT and sinus rhythm. The PDI measured during sinus rhythm was 579 +/- 240 microV-sec and the PDI during VT was 894 +/- 411 microV-sec (P < 0.001). In a subset of seven patients, PDIs were measured during VT, sinus rhythm, and ST induced by catecholamine infusion or exercise. In this subset, the PDI during sinus rhythm was 645 +/- 295 microV-sec, during ST 588 +/- 308 microV-sec (9% decrease from sinus, P = 0.05), and during VT 863 +/- 342 microV-sec (33.9% increase, P = 0.01). These data indicate that the measurement of the PDI is potentially useful in differentiating VT from ST.", "contents": "Differentiation between monomorphic ventricular tachycardia and sinus tachycardia based on the right ventricular evoked potential. The differentiation between ventricular tachycardia (VT) and sinus tachycardia (ST) is problematic in some patients with implantable defibrillators and/or antitachycardia pacemakers. The integral of the ventricular endocardial evoked response, or paced depolarization integral (PDI), has been demonstrated to undergo characteristic changes with a variety of stimuli including catecholamines, pacing rate, and exercise. We hypothesized that the PDI recorded from a unipolar transvenous right ventricular endocardial catheter would differentiate VT from ST. The PDI was calculated from a unipolar pacing stimulus, delivered via a cathode in the right ventricular apex, and the reference electrode, a quadripolar catheter positioned in the superior vena cava. PDIs were measured in 22 patients during VT and sinus rhythm. The PDI measured during sinus rhythm was 579 +/- 240 microV-sec and the PDI during VT was 894 +/- 411 microV-sec (P < 0.001). In a subset of seven patients, PDIs were measured during VT, sinus rhythm, and ST induced by catecholamine infusion or exercise. In this subset, the PDI during sinus rhythm was 645 +/- 295 microV-sec, during ST 588 +/- 308 microV-sec (9% decrease from sinus, P = 0.05), and during VT 863 +/- 342 microV-sec (33.9% increase, P = 0.01). These data indicate that the measurement of the PDI is potentially useful in differentiating VT from ST."} {"id": "PMID:1279533", "title": "Electrocardiographically documented unnecessary, spontaneous shocks in 241 patients with implantable cardioverter defibrillators.", "content": "The incidence and cause of electrocardiographically documented spontaneous implantable cardioverter defibrillator (ICD) discharges for a rhythm other than ventricular tachycardia (VT) or fibrillation (VF) (unnecessary shocks) were determined in 241 patients who underwent ICD implantation between March 1983 and November 1991. During follow-up of 24 +/- 20 months, 54 of 241 patients (22%) received a total of 132 unnecessary ICD shocks confirmed by Holter or telemetry monitoring or stored electrograms (Egs) from the ICD. The rhythm preceding these unnecessary ICD shocks was atrial fibrillation in 30 patients, sinus or supraventricular tachycardia (SVT) in 11 patients, antitachycardia pacing triggered by atrial fibrillation or SVT resulting in VT in 5 patients, nonsustained VT in 3 patients, and normal sinus or pacemaker rhythm in 10 patients. Unnecessary ICD discharges occurred most frequently during the first week after implantation or generator replacement (18 of 54 patients [33%]). Unnecessary ICD discharges could be documented more often by stored Egs in patients with devices with Eg storage capability (Ventritex Cadence, 19 of 54 patients [35%]) than by Holter or telemetry monitoring in patients with devices without Egs storage capabilities (34 of 193 patients [18%], P < 0.01), despite a shorter mean follow-up duration of 14 +/- 9 months versus 26 +/- 21 months, respectively. Only six of 54 patients (11%) in whom unnecessary ICD discharges occurred had recurrent unnecessary shocks during 22 +/- 20 months of follow-up after treatment directed at the cause of the first episode or device reprogramming to preclude non-VT rhythm detection.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Electrocardiographically documented unnecessary, spontaneous shocks in 241 patients with implantable cardioverter defibrillators. The incidence and cause of electrocardiographically documented spontaneous implantable cardioverter defibrillator (ICD) discharges for a rhythm other than ventricular tachycardia (VT) or fibrillation (VF) (unnecessary shocks) were determined in 241 patients who underwent ICD implantation between March 1983 and November 1991. During follow-up of 24 +/- 20 months, 54 of 241 patients (22%) received a total of 132 unnecessary ICD shocks confirmed by Holter or telemetry monitoring or stored electrograms (Egs) from the ICD. The rhythm preceding these unnecessary ICD shocks was atrial fibrillation in 30 patients, sinus or supraventricular tachycardia (SVT) in 11 patients, antitachycardia pacing triggered by atrial fibrillation or SVT resulting in VT in 5 patients, nonsustained VT in 3 patients, and normal sinus or pacemaker rhythm in 10 patients. Unnecessary ICD discharges occurred most frequently during the first week after implantation or generator replacement (18 of 54 patients [33%]). Unnecessary ICD discharges could be documented more often by stored Egs in patients with devices with Eg storage capability (Ventritex Cadence, 19 of 54 patients [35%]) than by Holter or telemetry monitoring in patients with devices without Egs storage capabilities (34 of 193 patients [18%], P < 0.01), despite a shorter mean follow-up duration of 14 +/- 9 months versus 26 +/- 21 months, respectively. Only six of 54 patients (11%) in whom unnecessary ICD discharges occurred had recurrent unnecessary shocks during 22 +/- 20 months of follow-up after treatment directed at the cause of the first episode or device reprogramming to preclude non-VT rhythm detection.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279534", "title": "Effects of an acute increase in atrial pressure on atrial refractoriness in humans.", "content": "Contraction-excitation feedback has been studied extensively in mammalian ventricles. In contrast, little is known about contraction-excitation feedback in mammalian atria. The objective of this study was to investigate the effect of acute alterations in atrial pressure, induced by varying the atrioventricular (AV) interval, on atrial refractoriness. Twenty patients without structural heart disease participated in the study. In each patient the atrial effective (ERP) and absolute refractory periods (ARP) were measured during AV pacing at a cycle length of 500 msec and an AV interval of 120 msec. Acute increases in atrial pressure were induced by pacing the atrium and ventricle simultaneously for the final two beats of the drive train. The ERP was defined as the longest extrastimulus coupling interval that failed to capture with an extrastimulus current strength of twice the stimulation threshold. The ARP was defined in a similar manner with an extrastimulus current strength of 10 mA. The ERP and ARP were determined using the incremental extrastimulus technique. A subset of patients had the pacing protocol performed during autonomic blockade. As the AV interval of the final two beats of the drive train was shortened from 120 msec to 0 msec, the peak right atrial pressure increased from 7 +/- 3 mmHg to 15 +/- 5 mmHg (P < 0.001). The increase in atrial pressure associated with simultaneous pacing of the atrium and ventricle resulted in shortening of the atrial ERP and ARP by 7.3 +/- 5.2 and 6.2 +/- 3.5 msec, respectively (P < 0.001). Similar results were obtained during autonomic blockade. these findings confirm the presence of contraction-excitation feedback in normal human atria.", "contents": "Effects of an acute increase in atrial pressure on atrial refractoriness in humans. Contraction-excitation feedback has been studied extensively in mammalian ventricles. In contrast, little is known about contraction-excitation feedback in mammalian atria. The objective of this study was to investigate the effect of acute alterations in atrial pressure, induced by varying the atrioventricular (AV) interval, on atrial refractoriness. Twenty patients without structural heart disease participated in the study. In each patient the atrial effective (ERP) and absolute refractory periods (ARP) were measured during AV pacing at a cycle length of 500 msec and an AV interval of 120 msec. Acute increases in atrial pressure were induced by pacing the atrium and ventricle simultaneously for the final two beats of the drive train. The ERP was defined as the longest extrastimulus coupling interval that failed to capture with an extrastimulus current strength of twice the stimulation threshold. The ARP was defined in a similar manner with an extrastimulus current strength of 10 mA. The ERP and ARP were determined using the incremental extrastimulus technique. A subset of patients had the pacing protocol performed during autonomic blockade. As the AV interval of the final two beats of the drive train was shortened from 120 msec to 0 msec, the peak right atrial pressure increased from 7 +/- 3 mmHg to 15 +/- 5 mmHg (P < 0.001). The increase in atrial pressure associated with simultaneous pacing of the atrium and ventricle resulted in shortening of the atrial ERP and ARP by 7.3 +/- 5.2 and 6.2 +/- 3.5 msec, respectively (P < 0.001). Similar results were obtained during autonomic blockade. these findings confirm the presence of contraction-excitation feedback in normal human atria."} {"id": "PMID:1279535", "title": "In anterior myocardial infarction, frequency domain is better than time domain analysis of the signal-averaged ECG for identifying patients at risk for sustained ventricular tachycardia.", "content": "Low amplitude signals at the end of the QRS in patients with prior myocardial infarction (MI) are related to fragmentation of the electrical impulse in ventricular myocardium and are known to correlate with an increased risk of sustained ventricular tachycardia (VT). We hypothesized that in patients with anterior MI (AMI), earlier activation of the damaged anterior wall would cause an earlier fragmentation of the signal-averaged ECG (SAECG) signal, making conventional time domain analysis of late potentials difficult. We performed SAECG in 213 patients (62 with AMI and 58 with inferior MI [IMI]). Fifty-seven had prior sustained VT; 23 with AMI and 24 with IMI. We examined the standard time domain SAECG parameters including the duration of the filtered QRS (40-250 Hz), the duration of the late QRS < 40 microV, and the root mean square amplitude of the last 40 msec of the QRS. We also examined the power law scaling (PLS) in the frequency domain. Receiver operating characteristic curve analysis of a discriminant function demonstrated significant differences for PLS as compared to time domain indices. An important finding was the significance of MI locus in the time domain indices. PLS did not exhibit this dependence. These data suggest that the usual indices are insufficient for identifying AMI patients at risk of VT. PLS, on the other hand, is valuable regardless of MI location.", "contents": "In anterior myocardial infarction, frequency domain is better than time domain analysis of the signal-averaged ECG for identifying patients at risk for sustained ventricular tachycardia. Low amplitude signals at the end of the QRS in patients with prior myocardial infarction (MI) are related to fragmentation of the electrical impulse in ventricular myocardium and are known to correlate with an increased risk of sustained ventricular tachycardia (VT). We hypothesized that in patients with anterior MI (AMI), earlier activation of the damaged anterior wall would cause an earlier fragmentation of the signal-averaged ECG (SAECG) signal, making conventional time domain analysis of late potentials difficult. We performed SAECG in 213 patients (62 with AMI and 58 with inferior MI [IMI]). Fifty-seven had prior sustained VT; 23 with AMI and 24 with IMI. We examined the standard time domain SAECG parameters including the duration of the filtered QRS (40-250 Hz), the duration of the late QRS < 40 microV, and the root mean square amplitude of the last 40 msec of the QRS. We also examined the power law scaling (PLS) in the frequency domain. Receiver operating characteristic curve analysis of a discriminant function demonstrated significant differences for PLS as compared to time domain indices. An important finding was the significance of MI locus in the time domain indices. PLS did not exhibit this dependence. These data suggest that the usual indices are insufficient for identifying AMI patients at risk of VT. PLS, on the other hand, is valuable regardless of MI location."} {"id": "PMID:1279536", "title": "Usefulness and adequacy of sensor data storage and retrieval for rate response simulation.", "content": "The usefulness of sensor data storage for rate response simulation was evaluated using a new dual chamber rate modulated pacemaker sensitive to acceleration forces (Relay 294-03 [Intermedics Inc.]). The pacemaker can store the sensor output during routine exercise and those values can be used to simulate rate profiles for other rate response settings. The predictive value of this feature was evaluated in three studies (mechanical, external pacemaker, and implanted pacemaker). In the first study, the pacemaker was submitted to three runs of eight different mechanical calibrated to-and-fro movements. In the second study, nine external pacemakers were strapped on healthy volunteers who performed three jogging tests. Finally, the predictive value of the simulation was studied in five implanted patients during three successive walking tests. In each study, the pacemaker was submitted three times to the same activity. The responsiveness was successively set to 5, 1, and 10, and the pacemaker outputs were continuously recorded on a Holter monitor. At the end of the first run, rate profile simulations for slopes 1 and 10 were performed; slope 5 rate response was simulated after the second run. A regression analysis was used to establish the correlation between predicted and achieved pacing rates for each study. The coefficients of correlation between predicted and measured pacing rates for the mechanical, external, and clinical studies were 0.999, 0.985, and 0.823, respectively. The corresponding slopes of regression lines were 1.005, 0.971, and 0.935. Calculated rate profile has a high predictive value and could be used to optimize rate responsive settings without serial exercise testings.", "contents": "Usefulness and adequacy of sensor data storage and retrieval for rate response simulation. The usefulness of sensor data storage for rate response simulation was evaluated using a new dual chamber rate modulated pacemaker sensitive to acceleration forces (Relay 294-03 [Intermedics Inc.]). The pacemaker can store the sensor output during routine exercise and those values can be used to simulate rate profiles for other rate response settings. The predictive value of this feature was evaluated in three studies (mechanical, external pacemaker, and implanted pacemaker). In the first study, the pacemaker was submitted to three runs of eight different mechanical calibrated to-and-fro movements. In the second study, nine external pacemakers were strapped on healthy volunteers who performed three jogging tests. Finally, the predictive value of the simulation was studied in five implanted patients during three successive walking tests. In each study, the pacemaker was submitted three times to the same activity. The responsiveness was successively set to 5, 1, and 10, and the pacemaker outputs were continuously recorded on a Holter monitor. At the end of the first run, rate profile simulations for slopes 1 and 10 were performed; slope 5 rate response was simulated after the second run. A regression analysis was used to establish the correlation between predicted and achieved pacing rates for each study. The coefficients of correlation between predicted and measured pacing rates for the mechanical, external, and clinical studies were 0.999, 0.985, and 0.823, respectively. The corresponding slopes of regression lines were 1.005, 0.971, and 0.935. Calculated rate profile has a high predictive value and could be used to optimize rate responsive settings without serial exercise testings."} {"id": "PMID:1279537", "title": "A unique preexcitation pattern related to an atypical anteroseptal accessory pathway.", "content": "Accessory atrioventricular pathways have traditionally been classified by anatomical location to four areas, namely anteroseptal, posteroseptal, and right and left free walls. Each of these have been associated with a relatively distinct preexicitation pattern electrocardiographically. We describe a patient with a unique ECG pattern suggesting preexicitation to the right ventricular outflow region. Preoperative and intraoperative electrophysiological testing confirmed the presence of an accessory pathway with an atrial insertion site near the His bundle, decremental anterograde conduction, and a ventricular insertion site in the upper part of the interventricular septum. Operative ablation near the atrial insertion site eliminated preexicitation.", "contents": "A unique preexcitation pattern related to an atypical anteroseptal accessory pathway. Accessory atrioventricular pathways have traditionally been classified by anatomical location to four areas, namely anteroseptal, posteroseptal, and right and left free walls. Each of these have been associated with a relatively distinct preexicitation pattern electrocardiographically. We describe a patient with a unique ECG pattern suggesting preexicitation to the right ventricular outflow region. Preoperative and intraoperative electrophysiological testing confirmed the presence of an accessory pathway with an atrial insertion site near the His bundle, decremental anterograde conduction, and a ventricular insertion site in the upper part of the interventricular septum. Operative ablation near the atrial insertion site eliminated preexicitation."} {"id": "PMID:1279538", "title": "Dissociation of atrioventricular conduction and refractoriness following application of radiofrequency energy to the canine atrioventricular node: acute and chronic observations.", "content": "The electrophysiology of AV nodal modification induced by radiofrequency energy (n = 5) or a sham procedure (n = 5) was studied in ten dogs. The five dogs that received radiofrequency energy had an AH prolongation > 100% from baseline values and this prolongation persisted throughout the 2-month study. The AV nodal functional refractory period was prolonged only acutely. These data indicate a dissociation between the effects on AV nodal conduction and refractoriness that was induced by this procedure. The five sham treated controls showed no acute or chronic electrophysiological changes. In the dogs that received radiofrequency energy, there was fibrosis of the approaches to the AV node and the region of the AV node itself. It is concluded that chronic modification of AV nodal conduction without concomitant changes in refractoriness can be induced by radiofrequency energy delivered in the proximal portion of the AV node. It would be anticipated that this procedure would not decrease the ventricular response to atrial fibrillation or flutter, may be effective in preventing AV nodal reentrant tachycardia by interfering with conduction either in the AV node or perinodal region. Since the AV node itself suffers at least moderate pathological damage, there may be an appreciable incidence of the late development of complete heart block after this procedure.", "contents": "Dissociation of atrioventricular conduction and refractoriness following application of radiofrequency energy to the canine atrioventricular node: acute and chronic observations. The electrophysiology of AV nodal modification induced by radiofrequency energy (n = 5) or a sham procedure (n = 5) was studied in ten dogs. The five dogs that received radiofrequency energy had an AH prolongation > 100% from baseline values and this prolongation persisted throughout the 2-month study. The AV nodal functional refractory period was prolonged only acutely. These data indicate a dissociation between the effects on AV nodal conduction and refractoriness that was induced by this procedure. The five sham treated controls showed no acute or chronic electrophysiological changes. In the dogs that received radiofrequency energy, there was fibrosis of the approaches to the AV node and the region of the AV node itself. It is concluded that chronic modification of AV nodal conduction without concomitant changes in refractoriness can be induced by radiofrequency energy delivered in the proximal portion of the AV node. It would be anticipated that this procedure would not decrease the ventricular response to atrial fibrillation or flutter, may be effective in preventing AV nodal reentrant tachycardia by interfering with conduction either in the AV node or perinodal region. Since the AV node itself suffers at least moderate pathological damage, there may be an appreciable incidence of the late development of complete heart block after this procedure."} {"id": "PMID:1279539", "title": "Effects of defibrillation shocks delivered directly over a major coronary artery.", "content": "This study investigated the influence of defibrillator shocks delivered directly over a coronary artery, independent of ventricular fibrillation, on cardiac hemodynamics. Thirty-six open chest, halothane anesthetized pigs were randomized to receive six shocks at one of 5.0, 7.5, or 10.0 joules (J). Shocks were delivered between two mesh electrodes (Medtronic TX-7) sutured onto the epicardium, one over the left anterior descending coronary artery and the second directly opposite on the posterobasal ventricular surface. Shock delivery was synchronized to the R wave of the cardiac cycle, to reduce the risk of inducing fibrillation, with a 5-minute stabilization period between successive shocks. Pressure from the left ventricle, the left anterior descending coronary artery, distal to the mesh electrode and the left circumflex (control) artery and contractility in the regions perfused by both arteries were measured. The shocks invariably produced an immediate (2-second postshock), but transient, depression in systolic pressure of the same magnitude for the left anterior descending coronary artery, circumflex artery and the left ventricle that recovered by 5-minute postshock. There was no dose dependent relationship to energy. Also there was no clear difference in myocardial wall motion between the area perfused by the left anterior descending coronary artery and that perfused by the circumflex artery. These results suggest that shocks up to 10 J delivered over an epicardial artery do not cause arterial spasm and do not compromise coronary artery blood flow.", "contents": "Effects of defibrillation shocks delivered directly over a major coronary artery. This study investigated the influence of defibrillator shocks delivered directly over a coronary artery, independent of ventricular fibrillation, on cardiac hemodynamics. Thirty-six open chest, halothane anesthetized pigs were randomized to receive six shocks at one of 5.0, 7.5, or 10.0 joules (J). Shocks were delivered between two mesh electrodes (Medtronic TX-7) sutured onto the epicardium, one over the left anterior descending coronary artery and the second directly opposite on the posterobasal ventricular surface. Shock delivery was synchronized to the R wave of the cardiac cycle, to reduce the risk of inducing fibrillation, with a 5-minute stabilization period between successive shocks. Pressure from the left ventricle, the left anterior descending coronary artery, distal to the mesh electrode and the left circumflex (control) artery and contractility in the regions perfused by both arteries were measured. The shocks invariably produced an immediate (2-second postshock), but transient, depression in systolic pressure of the same magnitude for the left anterior descending coronary artery, circumflex artery and the left ventricle that recovered by 5-minute postshock. There was no dose dependent relationship to energy. Also there was no clear difference in myocardial wall motion between the area perfused by the left anterior descending coronary artery and that perfused by the circumflex artery. These results suggest that shocks up to 10 J delivered over an epicardial artery do not cause arterial spasm and do not compromise coronary artery blood flow."} {"id": "PMID:1279540", "title": "Familial congenital sinus rhythm anomalies: clinical and pathological correlations.", "content": "We describe pathological abnormalities in a 72-year-old male member of a family with a congenital absence of sinus rhythm and a tendency to develop atrial fibrillation at an early age, and in a 54-year-old female member of a family with cardiomyopathy and progressive conduction system disease manifested by first-degree atrioventricular (AV) block, left bundle branch block, and atrial arrhythmias. Both patients died suddenly. The absence of sinus rhythm in case 1 could be explained by marked atrophy, degeneration, and isolation of the sinoatrial (SA) node. The SA node was also diseased in the member of the other family with atrial arrhythmias. Additional common features in both cases included: fatty metamorphosis and degenerative changes of the approaches to the SA node, the atrial preferential fibers, and the approaches to the AV node, a small AV node, degenerative changes of the bundle branches, and floppy AV valves. These findings show that the pathological substrate of familial supraventricular arrhythmias consists of a diffuse involvement of the entire conduction system, bearing resemblance to pathological findings in elderly subjects with acquired sick sinus syndrome.", "contents": "Familial congenital sinus rhythm anomalies: clinical and pathological correlations. We describe pathological abnormalities in a 72-year-old male member of a family with a congenital absence of sinus rhythm and a tendency to develop atrial fibrillation at an early age, and in a 54-year-old female member of a family with cardiomyopathy and progressive conduction system disease manifested by first-degree atrioventricular (AV) block, left bundle branch block, and atrial arrhythmias. Both patients died suddenly. The absence of sinus rhythm in case 1 could be explained by marked atrophy, degeneration, and isolation of the sinoatrial (SA) node. The SA node was also diseased in the member of the other family with atrial arrhythmias. Additional common features in both cases included: fatty metamorphosis and degenerative changes of the approaches to the SA node, the atrial preferential fibers, and the approaches to the AV node, a small AV node, degenerative changes of the bundle branches, and floppy AV valves. These findings show that the pathological substrate of familial supraventricular arrhythmias consists of a diffuse involvement of the entire conduction system, bearing resemblance to pathological findings in elderly subjects with acquired sick sinus syndrome."} {"id": "PMID:1279541", "title": "Correlation of electrophysiological activation patterns to tension generation in stimulated latissimus dorsi muscle.", "content": "Skeletal muscle has been used for biomechanical assist in experimental and clinical studies. Central to the success of these procedures is the generation of sufficient muscle force for the lifetime of the subject. Burst (tetanic) stimulation results in summation of individual twitches and generates higher power output. However, the superiority of paraneural versus intramuscular as well as proximal versus middle and distal intramuscular stimulations remains unclear. Electrophysiological mapping and mechanical performance of seven canine latissimus dorsi muscles were analyzed. The mechanism of higher tension generation produced by: (1) increased temporal summation; (2) greater motor units activated; or (3) result of both were determined. The parameters primarily dependent on the number of activated motor units are significantly greater following paraneural and proximal intramuscular stimulations. The parameters mainly related to temporal summation are not different between various electrode configurations. For intramuscular stimulation, it is the location of interelectrode field rather than the location of the cathode per se that determines the mechanical performance of the skeletal muscle. Furthermore, tension development of skeletal muscle is primary nerve activation rather than direct muscle stimulation. The higher tension generation that resulted from different electrode configurations is produced by activating a higher number of muscle fibers through the neuromuscular junctions.", "contents": "Correlation of electrophysiological activation patterns to tension generation in stimulated latissimus dorsi muscle. Skeletal muscle has been used for biomechanical assist in experimental and clinical studies. Central to the success of these procedures is the generation of sufficient muscle force for the lifetime of the subject. Burst (tetanic) stimulation results in summation of individual twitches and generates higher power output. However, the superiority of paraneural versus intramuscular as well as proximal versus middle and distal intramuscular stimulations remains unclear. Electrophysiological mapping and mechanical performance of seven canine latissimus dorsi muscles were analyzed. The mechanism of higher tension generation produced by: (1) increased temporal summation; (2) greater motor units activated; or (3) result of both were determined. The parameters primarily dependent on the number of activated motor units are significantly greater following paraneural and proximal intramuscular stimulations. The parameters mainly related to temporal summation are not different between various electrode configurations. For intramuscular stimulation, it is the location of interelectrode field rather than the location of the cathode per se that determines the mechanical performance of the skeletal muscle. Furthermore, tension development of skeletal muscle is primary nerve activation rather than direct muscle stimulation. The higher tension generation that resulted from different electrode configurations is produced by activating a higher number of muscle fibers through the neuromuscular junctions."} {"id": "PMID:1279542", "title": "The hemodynamic importance of atrial systole: a function of the kinetic energy of blood flow?", "content": "The relative importance of atrial systole on left ventricular filling was investigated at rest and during exercise in 25 patients with dual chamber pacemakers. The mean blood flow velocity over the mitral valve, the velocities of the rapid filling phase (E), the active filling phase (A), and the E/A ratio were determined by pulsed Doppler-echocardiography. The patients were first examined at rest during AV sequential pacing (DVI) at 70 and 104 beats/min. The investigation was subsequently repeated during atrial synchronous pacing (VDD) at rest and during supine submaximal exercise at workloads adjusted to achieve heart rates corresponding to those during DVI pacing. The mean blood flow velocity at rest did not differ between DVI and VDD pacing at 70 beats/min (0.46 vs 0.49 m/sec). When the resting heart rate was increased to 104 beats/min (DVI) the mean blood flow velocity increased to 0.56 msec (P < 0.001). At a corresponding heart rate during exercise (VDD) the velocity increased to 0.70 msec (P < 0.001). At a resting heart rate of 70 beats/min the E/A ratio (n = 14) did not differ significantly between DVI and VDD pacing. With an increased resting heart rate (DVI) the E/A ratio decreased from 0.94 +/- 0.45 to 0.78 +/- 0.18; NS. When the heart rate increased during exercise (VDD) the E/A ratio increased from 0.75 +/- 0.14 to 0.97 +/- 0.16; P < 0.001. There was a positive correlation between the increase of the mean blood flow velocity and the increase of the E/A ratio during exercise (r = 0.69, P < 0.01). No such correlation was found when the heart rate was changed at rest. Thus, the importance of atrial systole on ventricular filling diminishes during exercise in accordance with increasing blood flow velocity, which by physical principles is related to the kinetic energy. The relative importance of atrial systole is hence inversely correlated to the kinetic energy of the blood flow.", "contents": "The hemodynamic importance of atrial systole: a function of the kinetic energy of blood flow? The relative importance of atrial systole on left ventricular filling was investigated at rest and during exercise in 25 patients with dual chamber pacemakers. The mean blood flow velocity over the mitral valve, the velocities of the rapid filling phase (E), the active filling phase (A), and the E/A ratio were determined by pulsed Doppler-echocardiography. The patients were first examined at rest during AV sequential pacing (DVI) at 70 and 104 beats/min. The investigation was subsequently repeated during atrial synchronous pacing (VDD) at rest and during supine submaximal exercise at workloads adjusted to achieve heart rates corresponding to those during DVI pacing. The mean blood flow velocity at rest did not differ between DVI and VDD pacing at 70 beats/min (0.46 vs 0.49 m/sec). When the resting heart rate was increased to 104 beats/min (DVI) the mean blood flow velocity increased to 0.56 msec (P < 0.001). At a corresponding heart rate during exercise (VDD) the velocity increased to 0.70 msec (P < 0.001). At a resting heart rate of 70 beats/min the E/A ratio (n = 14) did not differ significantly between DVI and VDD pacing. With an increased resting heart rate (DVI) the E/A ratio decreased from 0.94 +/- 0.45 to 0.78 +/- 0.18; NS. When the heart rate increased during exercise (VDD) the E/A ratio increased from 0.75 +/- 0.14 to 0.97 +/- 0.16; P < 0.001. There was a positive correlation between the increase of the mean blood flow velocity and the increase of the E/A ratio during exercise (r = 0.69, P < 0.01). No such correlation was found when the heart rate was changed at rest. Thus, the importance of atrial systole on ventricular filling diminishes during exercise in accordance with increasing blood flow velocity, which by physical principles is related to the kinetic energy. The relative importance of atrial systole is hence inversely correlated to the kinetic energy of the blood flow."} {"id": "PMID:1279543", "title": "Factors predicting success in DC catheter ablation of accessory pathways.", "content": "In a series of 33 patients with accessory pathways, 26 had successful catheter ablation (fulguration [23 patients] or modification [3 patients]) of their accessory pathway conduction, and could be considered as a clinical success. One hundred thirteen single discharge or double discharge shocks were delivered, and each shock was studied to reveal which parameters were important to predict the success or failure of catheter ablation. Double discharge shocks resulted in successful accessory pathway modification or ablation twice as often as single discharge shocks (32% vs 16%). This effect was more pronounced in left lateral accessory pathways (48% vs 4%). Shocks in the electrophysiologically defined ventricular zone were more likely to be successful (33%) than shocks delivered in the atrial zone (14%), irrespective of accessory pathway location. The presence of a probable Kent potential was the parameter most strongly associated with success. The parameter most strongly associated with failure, with a 100% negative predictive value, was the absence of earliest activation recorded on the ablating catheter prior to shock delivery. An AV interval of < 60 msec significantly divided the successful from the unsuccessful shocks (P = 0.01). The VA interval during orthodromic reciprocating tachycardia or right ventricular stimulation did not allow for significant division into successful and unsuccessful attempts in this relatively short series. VA intervals, when longer, were predictive of failure but, when shorter, had low positive predictive value. Mean follow-up in 25 successful patients was 15 +/- 6 months. All patients did well in the follow-up period. Neither those patients with ablation nor modification of the accessory pathway had recurrent episodes of tachycardia or required pharmacological treatment for control of arrhythmias.", "contents": "Factors predicting success in DC catheter ablation of accessory pathways. In a series of 33 patients with accessory pathways, 26 had successful catheter ablation (fulguration [23 patients] or modification [3 patients]) of their accessory pathway conduction, and could be considered as a clinical success. One hundred thirteen single discharge or double discharge shocks were delivered, and each shock was studied to reveal which parameters were important to predict the success or failure of catheter ablation. Double discharge shocks resulted in successful accessory pathway modification or ablation twice as often as single discharge shocks (32% vs 16%). This effect was more pronounced in left lateral accessory pathways (48% vs 4%). Shocks in the electrophysiologically defined ventricular zone were more likely to be successful (33%) than shocks delivered in the atrial zone (14%), irrespective of accessory pathway location. The presence of a probable Kent potential was the parameter most strongly associated with success. The parameter most strongly associated with failure, with a 100% negative predictive value, was the absence of earliest activation recorded on the ablating catheter prior to shock delivery. An AV interval of < 60 msec significantly divided the successful from the unsuccessful shocks (P = 0.01). The VA interval during orthodromic reciprocating tachycardia or right ventricular stimulation did not allow for significant division into successful and unsuccessful attempts in this relatively short series. VA intervals, when longer, were predictive of failure but, when shorter, had low positive predictive value. Mean follow-up in 25 successful patients was 15 +/- 6 months. All patients did well in the follow-up period. Neither those patients with ablation nor modification of the accessory pathway had recurrent episodes of tachycardia or required pharmacological treatment for control of arrhythmias."} {"id": "PMID:1279544", "title": "Late potentials in a porcine model of anterior wall myocardial infarction and their relation to inducible ventricular tachycardia.", "content": "In this study, normal values for signal averaged electrocardiographic parameters were assessed in healthy pigs (n = 100) and the development of late potentials after myocardial infarction (n = 41) in relation to inducible ventricular tachycardia was investigated. Normal values are: filtered QRS duration (QRS) < or = 78 msec; root mean square voltage of the averaged QRS complex (V(tot)) > or = 51 microV, and duration of terminal activity below 30 microV (D30) < or = 37 msec. The distribution of the root mean square voltage in the last 30 msec (V30) was biphasic. Two weeks after myocardial infarction, QRS was prolonged from 55 +/- 10 to 66 +/- 19 msec (P < 0.002). D30 was prolonged from 19 +/- 6 msec to 28 +/- 13 (P < 0.002). V30 was decreased from 107 +/- 135 microV to 45 +/- 77 (P < 0.02). The total voltage (V(tot)) was decreased from 195 +/- 78 to 123 +/- 61 microV (P < 0.002). In four pigs (19%) late potentials developed. Sustained ventricular tachycardia was inducible in 11 pigs (52%), ventricular fibrillation in two pigs (10%) and eight pigs (38%) were noninducible. Three of 11 inducible pigs and one of the noninducible pigs had a late potential. The incidence of late potentials and their relation to inducible sustained ventricular tachycardia is comparable to the situation in man. Therefore, this pig model is an attractive alternative to the commonly used dog models.", "contents": "Late potentials in a porcine model of anterior wall myocardial infarction and their relation to inducible ventricular tachycardia. In this study, normal values for signal averaged electrocardiographic parameters were assessed in healthy pigs (n = 100) and the development of late potentials after myocardial infarction (n = 41) in relation to inducible ventricular tachycardia was investigated. Normal values are: filtered QRS duration (QRS) < or = 78 msec; root mean square voltage of the averaged QRS complex (V(tot)) > or = 51 microV, and duration of terminal activity below 30 microV (D30) < or = 37 msec. The distribution of the root mean square voltage in the last 30 msec (V30) was biphasic. Two weeks after myocardial infarction, QRS was prolonged from 55 +/- 10 to 66 +/- 19 msec (P < 0.002). D30 was prolonged from 19 +/- 6 msec to 28 +/- 13 (P < 0.002). V30 was decreased from 107 +/- 135 microV to 45 +/- 77 (P < 0.02). The total voltage (V(tot)) was decreased from 195 +/- 78 to 123 +/- 61 microV (P < 0.002). In four pigs (19%) late potentials developed. Sustained ventricular tachycardia was inducible in 11 pigs (52%), ventricular fibrillation in two pigs (10%) and eight pigs (38%) were noninducible. Three of 11 inducible pigs and one of the noninducible pigs had a late potential. The incidence of late potentials and their relation to inducible sustained ventricular tachycardia is comparable to the situation in man. Therefore, this pig model is an attractive alternative to the commonly used dog models."} {"id": "PMID:1279547", "title": "Intracardiac impedance to determine sympathetic activity in rate responsive pacing.", "content": "Modern pacemaker technology renders possible the adaptation of pacing rate to hemodynamic requirements. The most ambitious approach aims at restoration of the physiological closed-loop system by utilizing the information supplied by the autonomic nervous system (ANS) and extracted from myocardial contractile performance. Measurement is accomplished by the impedance method using the stimulation electrode as the measuring electrode. The ventricular inotropic parameter (VIP) has been identified as an ANS dependent parameter. A special detection algorithm, regional effective slope quantity (RQ), with high ANS sensitivity has been developed. Rate adaptation has been achieved by using an individually adjustable inotropic index (II). The concept has been evaluated in a multicenter study using a standardized exercise protocol. The results in patients with AV block demonstrate excellent agreement between spontaneous sinus rhythm and the ANS-controlled stimulation rate during different forms of exercise. Measurement of mean arterial blood pressure (MABP) supports the physiological approach of adapting the pacing rate to various types of hemodynamic challenges.", "contents": "Intracardiac impedance to determine sympathetic activity in rate responsive pacing. Modern pacemaker technology renders possible the adaptation of pacing rate to hemodynamic requirements. The most ambitious approach aims at restoration of the physiological closed-loop system by utilizing the information supplied by the autonomic nervous system (ANS) and extracted from myocardial contractile performance. Measurement is accomplished by the impedance method using the stimulation electrode as the measuring electrode. The ventricular inotropic parameter (VIP) has been identified as an ANS dependent parameter. A special detection algorithm, regional effective slope quantity (RQ), with high ANS sensitivity has been developed. Rate adaptation has been achieved by using an individually adjustable inotropic index (II). The concept has been evaluated in a multicenter study using a standardized exercise protocol. The results in patients with AV block demonstrate excellent agreement between spontaneous sinus rhythm and the ANS-controlled stimulation rate during different forms of exercise. Measurement of mean arterial blood pressure (MABP) supports the physiological approach of adapting the pacing rate to various types of hemodynamic challenges."} {"id": "PMID:1279548", "title": "Autonomic nervous system controlled closed loop cardiac pacing.", "content": "A multicenter clinical study is presented, which focuses on the reestablishment of closed loop cardiac control in patients with chronotropic insufficiency. Using the information about sympathetic tone contained in the myocardial contractility, it is possible to reconnect the heart rate to the physiological control mechanisms. Intracardiac impedance is measured with the ventricular electrode and the ventricular inotropic parameter (VIP) is derived from that. The VIP serves directly as input to the control of heart rate by the pacemaker. Over 200 patients have received autonomic nervous system (ANS) controlled pacemakers. The patient-pacemaker system was investigated in different ways. This included standard exercise tests, long-term studies of every day activities over 24 hours, psychological, and pharmacological challenges. To prove the validity of the approach we specifically looked at (1) the appropriateness of changes in paced heart rate with sympathetic tone during exercise, (2) the correlation between heart rate and sinus rate, if detectable, and (3) the correlation between the echocardiographically determined preejection period (PEP) and the VIP controlled heart rate.", "contents": "Autonomic nervous system controlled closed loop cardiac pacing. A multicenter clinical study is presented, which focuses on the reestablishment of closed loop cardiac control in patients with chronotropic insufficiency. Using the information about sympathetic tone contained in the myocardial contractility, it is possible to reconnect the heart rate to the physiological control mechanisms. Intracardiac impedance is measured with the ventricular electrode and the ventricular inotropic parameter (VIP) is derived from that. The VIP serves directly as input to the control of heart rate by the pacemaker. Over 200 patients have received autonomic nervous system (ANS) controlled pacemakers. The patient-pacemaker system was investigated in different ways. This included standard exercise tests, long-term studies of every day activities over 24 hours, psychological, and pharmacological challenges. To prove the validity of the approach we specifically looked at (1) the appropriateness of changes in paced heart rate with sympathetic tone during exercise, (2) the correlation between heart rate and sinus rate, if detectable, and (3) the correlation between the echocardiographically determined preejection period (PEP) and the VIP controlled heart rate."} {"id": "PMID:1279549", "title": "Identifying patients for rate responsive atrial pacing: a new method for patient selection and pacemaker programming.", "content": "In patients with sinus node disease (SND) and chronotropic incompetence, atrial rate adaptive stimulation (AAI,R pacing) is regarded as the most appropriate pacing mode. Since coronary artery disease is the most common etiology in these patients, we evaluated a new technique combining two-dimensional transesophageal echocardiography and atrial transesophageal pacing to detect pacing induced wall motion abnormalities and assess safe upper rate limits. Thirty-five patients were studied: 26 with and 9 without angiographic coronary artery disease. Stable atrial capture was achieved in all patients using 12 +/- 3 msec pulse width and 12 +/- 4 mA current strength. Sensitivity and specificity for the detection of coronary artery disease was highest for transesophageal echocardiography during pacing (sensitivity 81%, specificity 100%). Simultaneous 12-lead ECG during pacing had lower values (sensitivity 57%, specificity 75%). Pacing induced wall motion abnormalities preceded ST segment changes in all patients. Exercise stress testing showed similar values (sensitivity 62%, specificity 89%). It is concluded that simultaneous transesophageal echocardiography and transesophageal pacing is a safe and useful technique in selecting patients for AAI,R pacing and for the detection of safe upper rate limits, particularly when coronary artery disease is suspected.", "contents": "Identifying patients for rate responsive atrial pacing: a new method for patient selection and pacemaker programming. In patients with sinus node disease (SND) and chronotropic incompetence, atrial rate adaptive stimulation (AAI,R pacing) is regarded as the most appropriate pacing mode. Since coronary artery disease is the most common etiology in these patients, we evaluated a new technique combining two-dimensional transesophageal echocardiography and atrial transesophageal pacing to detect pacing induced wall motion abnormalities and assess safe upper rate limits. Thirty-five patients were studied: 26 with and 9 without angiographic coronary artery disease. Stable atrial capture was achieved in all patients using 12 +/- 3 msec pulse width and 12 +/- 4 mA current strength. Sensitivity and specificity for the detection of coronary artery disease was highest for transesophageal echocardiography during pacing (sensitivity 81%, specificity 100%). Simultaneous 12-lead ECG during pacing had lower values (sensitivity 57%, specificity 75%). Pacing induced wall motion abnormalities preceded ST segment changes in all patients. Exercise stress testing showed similar values (sensitivity 62%, specificity 89%). It is concluded that simultaneous transesophageal echocardiography and transesophageal pacing is a safe and useful technique in selecting patients for AAI,R pacing and for the detection of safe upper rate limits, particularly when coronary artery disease is suspected."} {"id": "PMID:1279550", "title": "Multicenter clinical evaluation of a new SSIR pacemaker.", "content": "A multicenter clinical evaluation of Sorin Swing 100, a new SSIR pacemaker with a gravimetric sensor, was performed by seven different centers enrolling a total of 89 patients, 56 men and 33 women, mean age 73.1 years, for pacemaker implantation (73 patients) or pacemaker replacement (16 patients). Pacing mode was VVIR in 73 patients and AAIR in 16. The behavior of pacing rate was evaluated 3 months after the implant by performing a 24-hour Holter monitor, an exercise stress test, and tests for the assessment of mechanical external interference (MEI). A physiological behavior of the paced rate was always observed during Holter monitoring. In 52 completely paced patients mean diurnal, nocturnal, and maximal heart rate were, respectively, 74.9 +/- 5.7 ppm, 58.1 +/- 5.8 ppm, and 113.4 +/- 12.7 ppm; a paced rate exceeding 100 ppm was reached on the average 5.6 times/Holter monitor. In all but two patients the sleep rate (55 ppm) was reached during the night or long resting time. During exercise stress test a direct correlation between the increase in pacing rate and the increase in workload was observed; the mean maximal heart rate reached in 49 completely paced patients was, respectively, 102.8 +/- 9 ppm in 17 patients who accomplished stage 1, 116.2 +/- 13.6 ppm in 28 patients who accomplished stage 2, and 133 +/- 6.7 ppm in 10 patients who accomplished stage 3 of the Bruce protocol. MEI testing never increased the pacing rate over the noise rate (10 ppm over the basic rate). In only seven patients the results obtained suggested to change the nominal set up of the pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Multicenter clinical evaluation of a new SSIR pacemaker. A multicenter clinical evaluation of Sorin Swing 100, a new SSIR pacemaker with a gravimetric sensor, was performed by seven different centers enrolling a total of 89 patients, 56 men and 33 women, mean age 73.1 years, for pacemaker implantation (73 patients) or pacemaker replacement (16 patients). Pacing mode was VVIR in 73 patients and AAIR in 16. The behavior of pacing rate was evaluated 3 months after the implant by performing a 24-hour Holter monitor, an exercise stress test, and tests for the assessment of mechanical external interference (MEI). A physiological behavior of the paced rate was always observed during Holter monitoring. In 52 completely paced patients mean diurnal, nocturnal, and maximal heart rate were, respectively, 74.9 +/- 5.7 ppm, 58.1 +/- 5.8 ppm, and 113.4 +/- 12.7 ppm; a paced rate exceeding 100 ppm was reached on the average 5.6 times/Holter monitor. In all but two patients the sleep rate (55 ppm) was reached during the night or long resting time. During exercise stress test a direct correlation between the increase in pacing rate and the increase in workload was observed; the mean maximal heart rate reached in 49 completely paced patients was, respectively, 102.8 +/- 9 ppm in 17 patients who accomplished stage 1, 116.2 +/- 13.6 ppm in 28 patients who accomplished stage 2, and 133 +/- 6.7 ppm in 10 patients who accomplished stage 3 of the Bruce protocol. MEI testing never increased the pacing rate over the noise rate (10 ppm over the basic rate). In only seven patients the results obtained suggested to change the nominal set up of the pacemaker.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279551", "title": "A new acceleration driven pacemaker: rate modulation versus normal sinus rhythm--comparison during treadmill exercise.", "content": "The pacing rate response of a new acceleration driven pulse generator (SWING 100, SORIN BIOMEDICA) was compared with simultaneous normal sinus rhythm (NSR) during two different treadmill exercises. This pacemaker has a gravitational acceleration sensor able to discriminate between physical activities and vibrations. Six healthy volunteers (three male, three female; aged 21.7 +/- 4.3 years), with the pacemaker strapped to their right infraclavicular area, performed each test three times with different rise response curve (RRC) each time: fast, normal, and slow. The fall response curve used was the same as the rising one during each test. Pacing rates were recorded using the VEGA analyzer (SORIN BIOMEDICA) and compared with simultaneous NSR recorded by a 7-channel ECG recorder (MINGOGRAF 7, SIEMENS). During all tests immediate (within seconds) rapid increase in pacemaker rate was seen up to about 60 seconds, then a slower increase followed thereafter. The mean correlation between pacing rates and NSR during the Bruce tests were 0.7941 +/- 0.10, 0.8562 +/- 0.14, and 0.8292 +/- 0.07; during the discontinuous tests 0.7292 +/- 0.16, 0.7233 +/- 0.10, and 0.7480 +/- 0.11 for fast, normal, and slow RRC, respectively. Each 30 seconds, nonsignificant differences were present between pacing rate and NSR during all the discontinuous tests; similar responses were observed only during the first two stages of Bruce tests after which NSR was significantly higher than pacemaker rates. The speed of rise to upper rate was the main difference between the different programs (fast, normal, and slow). The discontinuous tests showed that the pacemaker responds more to speed than to grade.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "A new acceleration driven pacemaker: rate modulation versus normal sinus rhythm--comparison during treadmill exercise. The pacing rate response of a new acceleration driven pulse generator (SWING 100, SORIN BIOMEDICA) was compared with simultaneous normal sinus rhythm (NSR) during two different treadmill exercises. This pacemaker has a gravitational acceleration sensor able to discriminate between physical activities and vibrations. Six healthy volunteers (three male, three female; aged 21.7 +/- 4.3 years), with the pacemaker strapped to their right infraclavicular area, performed each test three times with different rise response curve (RRC) each time: fast, normal, and slow. The fall response curve used was the same as the rising one during each test. Pacing rates were recorded using the VEGA analyzer (SORIN BIOMEDICA) and compared with simultaneous NSR recorded by a 7-channel ECG recorder (MINGOGRAF 7, SIEMENS). During all tests immediate (within seconds) rapid increase in pacemaker rate was seen up to about 60 seconds, then a slower increase followed thereafter. The mean correlation between pacing rates and NSR during the Bruce tests were 0.7941 +/- 0.10, 0.8562 +/- 0.14, and 0.8292 +/- 0.07; during the discontinuous tests 0.7292 +/- 0.16, 0.7233 +/- 0.10, and 0.7480 +/- 0.11 for fast, normal, and slow RRC, respectively. Each 30 seconds, nonsignificant differences were present between pacing rate and NSR during all the discontinuous tests; similar responses were observed only during the first two stages of Bruce tests after which NSR was significantly higher than pacemaker rates. The speed of rise to upper rate was the main difference between the different programs (fast, normal, and slow). The discontinuous tests showed that the pacemaker responds more to speed than to grade.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279552", "title": "A new motion responsive pacemaker: first clinical experience with an acceleration sensor pacemaker.", "content": "A new accelerometer-based adaptive rate pacemaker (EXCEL VR) was evaluated to investigate its behavior at nominal settings during treadmill exercise testing and postural changes. Eight patients with sinus rhythm were selected to compare intrinsic heart rate to sensor mediated rate. Throughout exercise treadmill testing, changes in the sensor mediated rate closely paralleled actual physiological changes. The Pearson product moment correlation of pacing rate with sinus frequency, calculated for all patients, was r = 0.82 (P = 0.001). Change in the patient's physical position resulted in immediate change in sensor rate, which corresponded appropriately to the type of position change and activity level. Average (+/- SD) pacing rate was 62.4 +/- 2.7 beats/min supine; 67 +/- 3.8 beats/min sitting; 69.8 +/- 6.4 beats/min standing; 81.6 +/- 8.7 beats/min slow walking; and 96.8 +/- 1.3 beats/min fast walking. After 4 minutes of recovery, the average pacing rate dropped to 65 +/- 3 beats/min. The interaction between the accelerometer and the pulse generator at nominal settings was accurate and infrequently required the use of its many programming options. The accelerometer sensor and pulse generator algorithm in this device during postural change and exercise resulted in physiological-like changes in sensor mediated heart rate.", "contents": "A new motion responsive pacemaker: first clinical experience with an acceleration sensor pacemaker. A new accelerometer-based adaptive rate pacemaker (EXCEL VR) was evaluated to investigate its behavior at nominal settings during treadmill exercise testing and postural changes. Eight patients with sinus rhythm were selected to compare intrinsic heart rate to sensor mediated rate. Throughout exercise treadmill testing, changes in the sensor mediated rate closely paralleled actual physiological changes. The Pearson product moment correlation of pacing rate with sinus frequency, calculated for all patients, was r = 0.82 (P = 0.001). Change in the patient's physical position resulted in immediate change in sensor rate, which corresponded appropriately to the type of position change and activity level. Average (+/- SD) pacing rate was 62.4 +/- 2.7 beats/min supine; 67 +/- 3.8 beats/min sitting; 69.8 +/- 6.4 beats/min standing; 81.6 +/- 8.7 beats/min slow walking; and 96.8 +/- 1.3 beats/min fast walking. After 4 minutes of recovery, the average pacing rate dropped to 65 +/- 3 beats/min. The interaction between the accelerometer and the pulse generator at nominal settings was accurate and infrequently required the use of its many programming options. The accelerometer sensor and pulse generator algorithm in this device during postural change and exercise resulted in physiological-like changes in sensor mediated heart rate."} {"id": "PMID:1279553", "title": "Clinical results of automatic slope adaptation in a dual sensor VVIR pacemaker.", "content": "Manual slope programming in rate adaptive pacemakers can be time consuming. This may become worse with dual sensor devices. The remedy is to let the pacemaker automatically learn the slopes. Fast learning replaces initial manual slope programming. Daily learning is a continuous process to determine and optimize slopes during daily life. Both methods are known for a QT sensing pacemaker. Fast learning is known for other single sensor devices. The aim of this study was to follow daily learning in a QT and activity dual sensor pacemaker, starting with factory slope settings. Six patients were studied for about 8 weeks. The daily learning algorithm appeared to be effective, showing the desired regulation processes. It took 2-5 weeks to reach full rate response.", "contents": "Clinical results of automatic slope adaptation in a dual sensor VVIR pacemaker. Manual slope programming in rate adaptive pacemakers can be time consuming. This may become worse with dual sensor devices. The remedy is to let the pacemaker automatically learn the slopes. Fast learning replaces initial manual slope programming. Daily learning is a continuous process to determine and optimize slopes during daily life. Both methods are known for a QT sensing pacemaker. Fast learning is known for other single sensor devices. The aim of this study was to follow daily learning in a QT and activity dual sensor pacemaker, starting with factory slope settings. Six patients were studied for about 8 weeks. The daily learning algorithm appeared to be effective, showing the desired regulation processes. It took 2-5 weeks to reach full rate response."} {"id": "PMID:1279554", "title": "Clinical observations with a dual sensor rate adaptive single chamber pacemaker.", "content": "The Topaz model 515 (Vitatron B.V.) is a dual sensor rate responsive pacemaker for single chamber stimulation. It can be driven by activity counts (ACT) and QT interval measurements. Inappropriate rate modulation due to one sensor can be corrected by \"sensor cross-checking.\" It was implanted in ten patients (20-86 years) of whom seven had complete heart block and atrial arrhythmias. After implantation T-wave amplitude ranged from 0.9 mV-3.5 mV. T-wave sensing ranged from 88%-99% in 9/10 patients at the follow-up of 3 weeks. Eight patients remained in default setting of the activity threshold, after evaluation with a short walking test. An exercise test was performed on all patients. In one test, QT sensing was marginal because of lead implantation in the right ventricular outflow tract. Therefore, this pacing rate was only modulated by ACT sensing. All others were tested with equal contribution of information from both sensors (ACT = QT). In 7/9, rate response was satisfactory. When the treadmill was repeated with ACT in five of these seven patients, rate generally accelerated too fast. In one patient the setting was adjusted to \"QT > ACT,\" because of inappropriate acceleration due to activity sensing, in another it was adjusted to \"QT < ACT\" because of delayed response to activity. The pacing rate and the ACT during treadmill tests in \"QT = ACT\" mode were more closely correlated in the first 3 minutes, compared with the last 3 minutes. We feel that rate modulation with this new pacemaker is adequate. Sensor blending and sensor cross-checking are of clinical importance.", "contents": "Clinical observations with a dual sensor rate adaptive single chamber pacemaker. The Topaz model 515 (Vitatron B.V.) is a dual sensor rate responsive pacemaker for single chamber stimulation. It can be driven by activity counts (ACT) and QT interval measurements. Inappropriate rate modulation due to one sensor can be corrected by \"sensor cross-checking.\" It was implanted in ten patients (20-86 years) of whom seven had complete heart block and atrial arrhythmias. After implantation T-wave amplitude ranged from 0.9 mV-3.5 mV. T-wave sensing ranged from 88%-99% in 9/10 patients at the follow-up of 3 weeks. Eight patients remained in default setting of the activity threshold, after evaluation with a short walking test. An exercise test was performed on all patients. In one test, QT sensing was marginal because of lead implantation in the right ventricular outflow tract. Therefore, this pacing rate was only modulated by ACT sensing. All others were tested with equal contribution of information from both sensors (ACT = QT). In 7/9, rate response was satisfactory. When the treadmill was repeated with ACT in five of these seven patients, rate generally accelerated too fast. In one patient the setting was adjusted to \"QT > ACT,\" because of inappropriate acceleration due to activity sensing, in another it was adjusted to \"QT < ACT\" because of delayed response to activity. The pacing rate and the ACT during treadmill tests in \"QT = ACT\" mode were more closely correlated in the first 3 minutes, compared with the last 3 minutes. We feel that rate modulation with this new pacemaker is adequate. Sensor blending and sensor cross-checking are of clinical importance."} {"id": "PMID:1279555", "title": "Follow-up of a minute ventilation rate adaptive pacemaker.", "content": "Although rate adaptive pacemakers are now frequently prescribed, there is limited information regarding long-term follow-up of patients with a pacemaker capable of rate adaptation. We have examined our patients in whom a pacemaker capable of rate adaptation via a sensor that determines minute ventilation has been implanted. After following a group of 42 patients for a mean of 13.2 months we have found this to be a reliable rate adaptive pacing system. The sensor was reliable long term, the system is easy to program, and sensor settings were changed infrequently.", "contents": "Follow-up of a minute ventilation rate adaptive pacemaker. Although rate adaptive pacemakers are now frequently prescribed, there is limited information regarding long-term follow-up of patients with a pacemaker capable of rate adaptation. We have examined our patients in whom a pacemaker capable of rate adaptation via a sensor that determines minute ventilation has been implanted. After following a group of 42 patients for a mean of 13.2 months we have found this to be a reliable rate adaptive pacing system. The sensor was reliable long term, the system is easy to program, and sensor settings were changed infrequently."} {"id": "PMID:1279556", "title": "Clinical experience with a new multiprogrammable dual chamber pacemaker.", "content": "We evaluated the clinical performance of a new dual chamber pacemaker, ELA Chorus, in 35 patients. This device incorporates linear rate adaptive AV delay (AVDR), rate smoothing, fallback, impedance telemetry, pacemaker mediated tachycardia (PMT) recognition and reprogramming software, intracardiac electrogram displays, autothreshold testing, diagnostic data, battery depletion curves, and laptop computer programming. Mean patient age was 68 years; 18 patients had AV block, six had sinus node dysfunction (one with AV block), nine had carotid sinus hypersensitivity (three with AV block), and two had vagally mediated syncope. At hospital discharge, programming was DDD with a mean low rate of 60 (50-70) beats/min, mean high rate of 126 (120-154) beats/min; AVDR was ON in 21 patients, rate smoothing ON in six patients, fallback ON in six patients, and PMT reprogramming algorithm ON in 27 patients. Pacemaker follow-up involved 500 clinic visits over 14.3 months (1-36). Three patients developed atrial fibrillation, reprogrammed to DDI mode (two patients) or fallback (one patient). Fallback was used 617 times. PMT occurred 427 times in six patients; the PMT algorithm reprogrammed AV delay and postventricular atrial refractory period (PVARP) automatically, a function unique to the Chorus. Intracardiac electrograms and autothreshold testing improved follow-up efficiency. This new dual chamber pacemaker enhances programming flexibility and improves diagnostic accuracy at follow-up.", "contents": "Clinical experience with a new multiprogrammable dual chamber pacemaker. We evaluated the clinical performance of a new dual chamber pacemaker, ELA Chorus, in 35 patients. This device incorporates linear rate adaptive AV delay (AVDR), rate smoothing, fallback, impedance telemetry, pacemaker mediated tachycardia (PMT) recognition and reprogramming software, intracardiac electrogram displays, autothreshold testing, diagnostic data, battery depletion curves, and laptop computer programming. Mean patient age was 68 years; 18 patients had AV block, six had sinus node dysfunction (one with AV block), nine had carotid sinus hypersensitivity (three with AV block), and two had vagally mediated syncope. At hospital discharge, programming was DDD with a mean low rate of 60 (50-70) beats/min, mean high rate of 126 (120-154) beats/min; AVDR was ON in 21 patients, rate smoothing ON in six patients, fallback ON in six patients, and PMT reprogramming algorithm ON in 27 patients. Pacemaker follow-up involved 500 clinic visits over 14.3 months (1-36). Three patients developed atrial fibrillation, reprogrammed to DDI mode (two patients) or fallback (one patient). Fallback was used 617 times. PMT occurred 427 times in six patients; the PMT algorithm reprogrammed AV delay and postventricular atrial refractory period (PVARP) automatically, a function unique to the Chorus. Intracardiac electrograms and autothreshold testing improved follow-up efficiency. This new dual chamber pacemaker enhances programming flexibility and improves diagnostic accuracy at follow-up."} {"id": "PMID:1279557", "title": "Facilitation of DDD follow-up using the DDT mode.", "content": "To facilitate follow-up, modern dual chamber pacemakers provide a variety of diagnostic features like ECG interpretation channels and intracardiac electrograms. For evaluation of the sensing performance at rest and during exercise, for assessment of the presence of crosstalk, and for measurement of the retrograde conduction time, dual chamber triggered pacing, particularly the DDT mode, can be used alternatively or additionally in pacemakers equipped with this option. In contrast to ECG interpretation channels, ECG documentation is not required for evaluation of the sensing performance, because the triggered pulses serving as markers for sense events can also be seen on the monitor. Selection of the DDT mode not only as temporary but also as permanent program serves to facilitate pacemaker ECG interpretation for exercise tests and Holter recordings as well.", "contents": "Facilitation of DDD follow-up using the DDT mode. To facilitate follow-up, modern dual chamber pacemakers provide a variety of diagnostic features like ECG interpretation channels and intracardiac electrograms. For evaluation of the sensing performance at rest and during exercise, for assessment of the presence of crosstalk, and for measurement of the retrograde conduction time, dual chamber triggered pacing, particularly the DDT mode, can be used alternatively or additionally in pacemakers equipped with this option. In contrast to ECG interpretation channels, ECG documentation is not required for evaluation of the sensing performance, because the triggered pulses serving as markers for sense events can also be seen on the monitor. Selection of the DDT mode not only as temporary but also as permanent program serves to facilitate pacemaker ECG interpretation for exercise tests and Holter recordings as well."} {"id": "PMID:1279558", "title": "External vibration interference of activity based rate responsive pacemakers.", "content": "The change of the pacing rate in response to external vibration interference was assessed in four rate responsive pacemakers with a piezoelectric crystal (Medtronic Activitrax 8403, Siemens Sensolog 3, Biotronik Ergos 01, and Medtronic Legend 8417) and one with an accelerometer (CPI Excel VR 1119). They were tested in the laboratory. External vibration was simulated in vitro by exposing the different pacemakers to a controlled sinusoidal vibration force generated by a Millar pressure vibration amplifier type MGM-30 (Millar Instruments, Inc., Houston, TX, USA). All pacemakers were programmed at standard settings. Two types of vibration forces were applied: (1) one with varying amplitude but with constant vibration frequency; and (2) one with varying frequency but with constant vibration amplitude. In this manner curves of pacing rate versus vibration forces versus vibration frequency were obtained. High vibration forces and low vibration frequencies were associated with the highest pacing rate response. In this experimental setting, the pacemaker based on the accelerometer principle apparently was the least sensitive to high frequency vibrations, which are known to be related to environmental interference. It also seemed more appropriately responsive in the lower frequency range, which is more appropriate for the detection of true physiological activity.", "contents": "External vibration interference of activity based rate responsive pacemakers. The change of the pacing rate in response to external vibration interference was assessed in four rate responsive pacemakers with a piezoelectric crystal (Medtronic Activitrax 8403, Siemens Sensolog 3, Biotronik Ergos 01, and Medtronic Legend 8417) and one with an accelerometer (CPI Excel VR 1119). They were tested in the laboratory. External vibration was simulated in vitro by exposing the different pacemakers to a controlled sinusoidal vibration force generated by a Millar pressure vibration amplifier type MGM-30 (Millar Instruments, Inc., Houston, TX, USA). All pacemakers were programmed at standard settings. Two types of vibration forces were applied: (1) one with varying amplitude but with constant vibration frequency; and (2) one with varying frequency but with constant vibration amplitude. In this manner curves of pacing rate versus vibration forces versus vibration frequency were obtained. High vibration forces and low vibration frequencies were associated with the highest pacing rate response. In this experimental setting, the pacemaker based on the accelerometer principle apparently was the least sensitive to high frequency vibrations, which are known to be related to environmental interference. It also seemed more appropriately responsive in the lower frequency range, which is more appropriate for the detection of true physiological activity."} {"id": "PMID:1279559", "title": "Atrial arrhythmias in dual chamber pacing and their influence on long-term mortality.", "content": "A retrospective study of 252 patients who received a DDD pacemaker between October 1982 and December 1990 was performed. During a mean follow-up of 30 months, reprogramming to the VVI mode was necessary in 39 patients (15.5%). Technical problems causing downgrading occurred 15 times, of which 13 problems became permanent. A total number of 24 patients had sustained atrial arrhythmias, including 14 with atrial fibrillation and 10 with atrial flutter. In this group, conversion to sinus rhythm could be obtained in 38%. After 2 years, reliable DDD pacing was maintained in 86% of the surviving patients. The survival after 1 and 2 years was 94% and 89%, respectively, and was not influenced by arrhythmias or technical problems. We conclude that atrial arrhythmias including flutter are the most important reasons for reprogramming to the VVI mode, although in an important number of patients, predominantly those with flutter, restoration of AV synchrony can be obtained. The high number of patients with atrial flutter could imply some role for DDD devices offering the option of antitachycardia pacing. Reprogramming of the pacing mode did not influence mortality.", "contents": "Atrial arrhythmias in dual chamber pacing and their influence on long-term mortality. A retrospective study of 252 patients who received a DDD pacemaker between October 1982 and December 1990 was performed. During a mean follow-up of 30 months, reprogramming to the VVI mode was necessary in 39 patients (15.5%). Technical problems causing downgrading occurred 15 times, of which 13 problems became permanent. A total number of 24 patients had sustained atrial arrhythmias, including 14 with atrial fibrillation and 10 with atrial flutter. In this group, conversion to sinus rhythm could be obtained in 38%. After 2 years, reliable DDD pacing was maintained in 86% of the surviving patients. The survival after 1 and 2 years was 94% and 89%, respectively, and was not influenced by arrhythmias or technical problems. We conclude that atrial arrhythmias including flutter are the most important reasons for reprogramming to the VVI mode, although in an important number of patients, predominantly those with flutter, restoration of AV synchrony can be obtained. The high number of patients with atrial flutter could imply some role for DDD devices offering the option of antitachycardia pacing. Reprogramming of the pacing mode did not influence mortality."} {"id": "PMID:1279560", "title": "Mixed microprocessor-random logic approach for innovative pacing systems.", "content": "Modern pacing systems are becoming more and more sophisticated. Conversion of the information supplied by a sensor into suitable parameters for a rate controlling algorithm and the management of complex timing are common tasks for an integrated circuit (IC) in cardiac pacing. An effective solution consists of using a microprocessor to implement algorithms and pacing modes in a flexible way. The key point of using the same hardware resources for different tasks on a time sharing basis allows the design of a less complex IC when compared to a random logic structure with the same performances. The major design problems in a full microprocessor solution are its relatively low operating speed due to the low frequency clock necessary for low current drain, and the sequential structure of the machine itself. This can lead to unacceptable timing inaccuracy in all situations requiring the management of complex decision trees. In order to take full benefit from the advantages of a microprocessor structure without these drawbacks, a mixed microprocessor-random logic approach has been investigated. This architecture uses a microprocessor core to perform all high level nonreal-time operations (setup of the pacing cycle, data reduction and processing, data integrity checks) while a set of random logic peripherals is used for all critical timing aspects.", "contents": "Mixed microprocessor-random logic approach for innovative pacing systems. Modern pacing systems are becoming more and more sophisticated. Conversion of the information supplied by a sensor into suitable parameters for a rate controlling algorithm and the management of complex timing are common tasks for an integrated circuit (IC) in cardiac pacing. An effective solution consists of using a microprocessor to implement algorithms and pacing modes in a flexible way. The key point of using the same hardware resources for different tasks on a time sharing basis allows the design of a less complex IC when compared to a random logic structure with the same performances. The major design problems in a full microprocessor solution are its relatively low operating speed due to the low frequency clock necessary for low current drain, and the sequential structure of the machine itself. This can lead to unacceptable timing inaccuracy in all situations requiring the management of complex decision trees. In order to take full benefit from the advantages of a microprocessor structure without these drawbacks, a mixed microprocessor-random logic approach has been investigated. This architecture uses a microprocessor core to perform all high level nonreal-time operations (setup of the pacing cycle, data reduction and processing, data integrity checks) while a set of random logic peripherals is used for all critical timing aspects."} {"id": "PMID:1279561", "title": "Clinical interest of a sensor driven algorithm limiting ventricular pacing rate during supraventricular tachycardia in dual chamber pacing.", "content": "A sensor driven algorithm limiting ventricular pacing rate during supraventricular tachycardia (SVT) is included in a dual chamber rate modulated pacemaker sensitive to acceleration forces (Relay, 294-03, Intermedics Inc.). According to the intensity of concomitant exercise, the ventricular pacing rate is limited either to the programmed maximum pacing rate (MPR) or to an interim lower limit, called \"conditional ventricular tracking limit\" (CVTL). The MPR prevails over the CVTL when the sensor calculated pacing rate exceeds the minimal rate by more than 20 beats/min. The purpose of the study is to determine the clinical safety and efficacy of this algorithm in patients with intermittent SVT. A Relay was implanted in four patients with a bradycardia/tachycardia syndrome and in four patients with complete atrioventricular block (CAVB). All had episodes of paroxysmal atrial tachycardia. The units were programmed in DDDR: rate responsive parameters were adjusted by simulating the rate response during three levels of exercise to let the MPR override the CVTL only during strenuous exercise. Holter monitors and exercise testings were performed at 3-month follow-up. In seven patients, Holter recordings showed supraventricular arrhythmias at rest with a ventricular pacing rate limited to the CVTL. Appropriate rate increases during exercise testings were also demonstrated. Three devices had to be reprogrammed in DDIR (one patient suffering from nearly permanent atrial flutter and two patients not tolerating the CVTL pacing rate at rest). The CVTL algorithm is effective in protecting against high ventricular pacing rates during supraventricular arrhythmias. It allows the selection of the DDDR mode even with a high MPR in patients with intermittent SVT.", "contents": "Clinical interest of a sensor driven algorithm limiting ventricular pacing rate during supraventricular tachycardia in dual chamber pacing. A sensor driven algorithm limiting ventricular pacing rate during supraventricular tachycardia (SVT) is included in a dual chamber rate modulated pacemaker sensitive to acceleration forces (Relay, 294-03, Intermedics Inc.). According to the intensity of concomitant exercise, the ventricular pacing rate is limited either to the programmed maximum pacing rate (MPR) or to an interim lower limit, called \"conditional ventricular tracking limit\" (CVTL). The MPR prevails over the CVTL when the sensor calculated pacing rate exceeds the minimal rate by more than 20 beats/min. The purpose of the study is to determine the clinical safety and efficacy of this algorithm in patients with intermittent SVT. A Relay was implanted in four patients with a bradycardia/tachycardia syndrome and in four patients with complete atrioventricular block (CAVB). All had episodes of paroxysmal atrial tachycardia. The units were programmed in DDDR: rate responsive parameters were adjusted by simulating the rate response during three levels of exercise to let the MPR override the CVTL only during strenuous exercise. Holter monitors and exercise testings were performed at 3-month follow-up. In seven patients, Holter recordings showed supraventricular arrhythmias at rest with a ventricular pacing rate limited to the CVTL. Appropriate rate increases during exercise testings were also demonstrated. Three devices had to be reprogrammed in DDIR (one patient suffering from nearly permanent atrial flutter and two patients not tolerating the CVTL pacing rate at rest). The CVTL algorithm is effective in protecting against high ventricular pacing rates during supraventricular arrhythmias. It allows the selection of the DDDR mode even with a high MPR in patients with intermittent SVT."} {"id": "PMID:1279562", "title": "In vitro evaluation of a sensor sensitive to acceleration forces included in a new rate modulated pacemaker.", "content": "The characteristics of the sensor and rate adaptive algorithm included in a new dual chamber rate responsive pacemaker (Relay 294-03, Intermedics, Inc.) were studied by submitting the device to calibrated to-and-fro movements of specific frequencies and peak accelerations by means of a mechanical arm connected to a speed adapter. Atrial pacing rate was continuously recorded on a Holter monitor. The influences of the frequency, the magnitude, and the axis of the acceleration forces as well as the reproducibility of the rate response were evaluated. (1) The sensor was sensitive to frequencies ranging from 0.5 to 7 Hz with a peak sensitivity at 3 Hz; (2) the pacing rate was not affected during movements at frequencies > 6 Hz, commonly presented as nonactivity related signals (car, bus transportation, drilling....); (3) the pacing rate increased as a function of the acceleration magnitude up to 0.5 G (0.3 G for 3 Hz), then remained constant. This level of acceleration usually corresponds to high degrees of activity; (4) rate response was maximum when acceleration was directed in the anteroposterior direction; (5) reproducibility of the rate response was excellent (R2: 0.999; slope of the regression line: 0.999). Relay 294-03 is a low frequency signal sensing rate modulated pacemaker using an accelerometer sensitive to motion, mainly in the anteroposterior direction.", "contents": "In vitro evaluation of a sensor sensitive to acceleration forces included in a new rate modulated pacemaker. The characteristics of the sensor and rate adaptive algorithm included in a new dual chamber rate responsive pacemaker (Relay 294-03, Intermedics, Inc.) were studied by submitting the device to calibrated to-and-fro movements of specific frequencies and peak accelerations by means of a mechanical arm connected to a speed adapter. Atrial pacing rate was continuously recorded on a Holter monitor. The influences of the frequency, the magnitude, and the axis of the acceleration forces as well as the reproducibility of the rate response were evaluated. (1) The sensor was sensitive to frequencies ranging from 0.5 to 7 Hz with a peak sensitivity at 3 Hz; (2) the pacing rate was not affected during movements at frequencies > 6 Hz, commonly presented as nonactivity related signals (car, bus transportation, drilling....); (3) the pacing rate increased as a function of the acceleration magnitude up to 0.5 G (0.3 G for 3 Hz), then remained constant. This level of acceleration usually corresponds to high degrees of activity; (4) rate response was maximum when acceleration was directed in the anteroposterior direction; (5) reproducibility of the rate response was excellent (R2: 0.999; slope of the regression line: 0.999). Relay 294-03 is a low frequency signal sensing rate modulated pacemaker using an accelerometer sensitive to motion, mainly in the anteroposterior direction."} {"id": "PMID:1279563", "title": "Feasibility of using intracardiac impedance measurements for capture detection.", "content": "Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation energy. While with technological progress the electronics' energy consumption has been reduced significantly, clinical practice shows that many cardiac pacemakers are programmed to suboptimal settings with regard to minimization of pacing energy consumption. Several methods for optimizing pacemaker output settings have been proposed in the past. The most promising concept is an output parameter optimizing pacemaker with automatic capture detection. We examined whether it is possible to distinguish between effective and ineffective pacemaker stimulus capture by analyzing high pass filtered intracardiac impedance signals that are derived from standard bipolar pacing leads. In one series of 11 patients undergoing replacement or implantation of chronic bipolar pacemakers, four patients during electrophysiology studies, and eight volunteers undergoing invasive electrophysiology trials, we examined intracardiac impedance signals obtained with various stimulation rates and output parameter settings. Additionally we analyzed a series of five patients with implanted pacemakers that can measure and telemeter intracardiac impedance signals. Several evaluation concepts have been analyzed regarding their ability to discriminate between effective and ineffective stimuli. We developed an adequate algorithm that detects capture or loss of capture at different output parameter settings based on intracardiac impedance analysis. The sensitivity is 98.5% and specificity is 91% to loss of capture for the currently investigated algorithm and this can be used to determine the optimal setting of pulse width and amplitude with regard to energy consumption. This concept is currently under realization in the external programmer and in the future an implementation of these algorithms within the pacemaker itself is intended.", "contents": "Feasibility of using intracardiac impedance measurements for capture detection. Energy consumption and longevity of modern pacemakers are determined by the controlling electronic circuitry and by the stimulation energy. While with technological progress the electronics' energy consumption has been reduced significantly, clinical practice shows that many cardiac pacemakers are programmed to suboptimal settings with regard to minimization of pacing energy consumption. Several methods for optimizing pacemaker output settings have been proposed in the past. The most promising concept is an output parameter optimizing pacemaker with automatic capture detection. We examined whether it is possible to distinguish between effective and ineffective pacemaker stimulus capture by analyzing high pass filtered intracardiac impedance signals that are derived from standard bipolar pacing leads. In one series of 11 patients undergoing replacement or implantation of chronic bipolar pacemakers, four patients during electrophysiology studies, and eight volunteers undergoing invasive electrophysiology trials, we examined intracardiac impedance signals obtained with various stimulation rates and output parameter settings. Additionally we analyzed a series of five patients with implanted pacemakers that can measure and telemeter intracardiac impedance signals. Several evaluation concepts have been analyzed regarding their ability to discriminate between effective and ineffective stimuli. We developed an adequate algorithm that detects capture or loss of capture at different output parameter settings based on intracardiac impedance analysis. The sensitivity is 98.5% and specificity is 91% to loss of capture for the currently investigated algorithm and this can be used to determine the optimal setting of pulse width and amplitude with regard to energy consumption. This concept is currently under realization in the external programmer and in the future an implementation of these algorithms within the pacemaker itself is intended."} {"id": "PMID:1279564", "title": "Reliability of an automatic sensing algorithm.", "content": "Automatic adaptation of the atrial sensitivity was evaluated in 18 patients with dual chamber pacemakers (Intermedics, Inc., Relay) in the unipolar mode. After atrial sensitivity was stabilized in the upright position, patients underwent a 1.0 W/kg body weight exercise for 5 minutes. A 24-hour Holter ECG was recorded, and the maximum and minimum atrial sensitivity values reached were stored in the memory of the pulse generator. In a second series of 12 patients, Holter ECGs were recorded twice, starting with the same sensitivity but with automatic adaptation alternately switched \"on\" or \"off.\" Results of the exercise test: mean atrial sensitivity declined from 2.30 +/- 0.77 mV to 2.03 +/- 0.68 mV. There was no change in five patients, a slight increase in two patients, and lowering of the atrial sensitivity was observed in 11 patients, the difference ranging from 0.2 to 1.0 mV. A total of two P waves in two patients were missed by the atrial amplifier. The minimum and maximum sensitivity reached during Holter monitoring averaged 2.31 +/- 0.67 mV versus 1.72 +/- 0.71 mV (difference 0-1.7 mV). Normal pacemaker function was found in six patients, including one patient without any intrinsic atrial activity. Malsensing of less than five P waves occurred in four patients. More than 50 sensing defects resulted from ectopic atrial beats (four patients). We observed atrial oversensing in three cases; one patient showed atrial over- and undersensing. The comparison between fixed and variable sensitivity did not reveal any superiority of automatic adaptation.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Reliability of an automatic sensing algorithm. Automatic adaptation of the atrial sensitivity was evaluated in 18 patients with dual chamber pacemakers (Intermedics, Inc., Relay) in the unipolar mode. After atrial sensitivity was stabilized in the upright position, patients underwent a 1.0 W/kg body weight exercise for 5 minutes. A 24-hour Holter ECG was recorded, and the maximum and minimum atrial sensitivity values reached were stored in the memory of the pulse generator. In a second series of 12 patients, Holter ECGs were recorded twice, starting with the same sensitivity but with automatic adaptation alternately switched \"on\" or \"off.\" Results of the exercise test: mean atrial sensitivity declined from 2.30 +/- 0.77 mV to 2.03 +/- 0.68 mV. There was no change in five patients, a slight increase in two patients, and lowering of the atrial sensitivity was observed in 11 patients, the difference ranging from 0.2 to 1.0 mV. A total of two P waves in two patients were missed by the atrial amplifier. The minimum and maximum sensitivity reached during Holter monitoring averaged 2.31 +/- 0.67 mV versus 1.72 +/- 0.71 mV (difference 0-1.7 mV). Normal pacemaker function was found in six patients, including one patient without any intrinsic atrial activity. Malsensing of less than five P waves occurred in four patients. More than 50 sensing defects resulted from ectopic atrial beats (four patients). We observed atrial oversensing in three cases; one patient showed atrial over- and undersensing. The comparison between fixed and variable sensitivity did not reveal any superiority of automatic adaptation.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279565", "title": "A comparison of external rate responsive pacemakers with identical implanted units.", "content": "Seven patients with previously implanted accelerometer-based DDDR pacemakers had an identically programmed external pacemaker taped onto their chest. Both units underwent a simultaneous test to set the sensitivity of the accelerometer. The units were then programmed to record the pacing rates for a 15-minute period. The patients underwent an exercise course that included walking and stairs. After the exercise, the patients sat for 3 minutes and the pacing rates from the test were telemetered. The pacing rate was compared at 2 minutes, 4 minutes, peak, and 3 minutes postexercise. The mean standard deviation (SED) for the external pacemaker was 97.9 at 3.53 ppm, 102 at 10.6 ppm, 106 at 8.94 ppm, and 71.3 at 2.29 ppm at 2, 4, peak, and decay, respectively. The mean SED for the implanted pacemaker was 98.1 at 5.76 ppm, 100 at 10.2 ppm, 104 8.24 ppm, 72.4 at 2.88 ppm at 2, 4, peak, and decay, respectively. Difference between pacemakers in ppm was 0.286, 2.0, 2.71, and 1.14 at 2, 4, peak, and decay, respectively. A 95% confidence interval in ppm was -5.28 to 5.85, -10.1 to 14.1, -7.30 to 12.7, and -1.89 to 4.17 at 2, 4, peak, and decay, respectively. In all patients there was a high confidence correlation between the implanted and external unit. An external unit can be used to predict the rate response of an accelerometer-based pacemaker without any adjustments to the pacing parameters.", "contents": "A comparison of external rate responsive pacemakers with identical implanted units. Seven patients with previously implanted accelerometer-based DDDR pacemakers had an identically programmed external pacemaker taped onto their chest. Both units underwent a simultaneous test to set the sensitivity of the accelerometer. The units were then programmed to record the pacing rates for a 15-minute period. The patients underwent an exercise course that included walking and stairs. After the exercise, the patients sat for 3 minutes and the pacing rates from the test were telemetered. The pacing rate was compared at 2 minutes, 4 minutes, peak, and 3 minutes postexercise. The mean standard deviation (SED) for the external pacemaker was 97.9 at 3.53 ppm, 102 at 10.6 ppm, 106 at 8.94 ppm, and 71.3 at 2.29 ppm at 2, 4, peak, and decay, respectively. The mean SED for the implanted pacemaker was 98.1 at 5.76 ppm, 100 at 10.2 ppm, 104 8.24 ppm, 72.4 at 2.88 ppm at 2, 4, peak, and decay, respectively. Difference between pacemakers in ppm was 0.286, 2.0, 2.71, and 1.14 at 2, 4, peak, and decay, respectively. A 95% confidence interval in ppm was -5.28 to 5.85, -10.1 to 14.1, -7.30 to 12.7, and -1.89 to 4.17 at 2, 4, peak, and decay, respectively. In all patients there was a high confidence correlation between the implanted and external unit. An external unit can be used to predict the rate response of an accelerometer-based pacemaker without any adjustments to the pacing parameters."} {"id": "PMID:1279566", "title": "Italian multicenter study on a single lead VDD pacing system using a narrow atrial dipole spacing.", "content": "Since November 1988, 514 patients with advanced atrioventricular (AV) block and normal sinoatrial function have received the single lead VDD pacing system Twinal 30 Lem/CCS in 30 Italian centers. At implantation, particular attention was paid to the correct positioning of the atrial dipole in the mid- to mid-high right atrium and to the atrial electrogram characteristics. The follow-up included a chest X ray, to be performed before discharge of the patient from the hospital, telemetric evaluations of the endoatrial potential, provocative tests for interferences by myopotentials, 24-hour ambulatory EGG recordings, and where possible, exercise stress tests. The mean follow-up duration was 15.2 months, ranging from 1 to 42 months. A very low percentage of chronic atrial fibrillation, loss of atrial sensing, and system replacement was reported, most of the patients (93.5%) being paced in VDD mode. All investigations indicated an excellent overall system performance, stable AV synchrony, and infrequent myopotential interference, and a low complication rate throughout the follow-up period.", "contents": "Italian multicenter study on a single lead VDD pacing system using a narrow atrial dipole spacing. Since November 1988, 514 patients with advanced atrioventricular (AV) block and normal sinoatrial function have received the single lead VDD pacing system Twinal 30 Lem/CCS in 30 Italian centers. At implantation, particular attention was paid to the correct positioning of the atrial dipole in the mid- to mid-high right atrium and to the atrial electrogram characteristics. The follow-up included a chest X ray, to be performed before discharge of the patient from the hospital, telemetric evaluations of the endoatrial potential, provocative tests for interferences by myopotentials, 24-hour ambulatory EGG recordings, and where possible, exercise stress tests. The mean follow-up duration was 15.2 months, ranging from 1 to 42 months. A very low percentage of chronic atrial fibrillation, loss of atrial sensing, and system replacement was reported, most of the patients (93.5%) being paced in VDD mode. All investigations indicated an excellent overall system performance, stable AV synchrony, and infrequent myopotential interference, and a low complication rate throughout the follow-up period."} {"id": "PMID:1279567", "title": "Initial clinical experience with a single pass VDDR pacing system.", "content": "Although ventricular rate adaptive pacing (VVIR) improves exercise capacity and cardiac output compared to constant rate ventricular pacing (VVI), this pacing mode does not provide benefit of atrioventricular (AV) synchrony. We evaluated the use of a custom-built VDDR pacing system using a single pass, ventricular lead, which detects endocavity P wave using a pair of diagonally arranged atrial bipolar (DAB) electrodes. In the VDDR mode, AV synchrony is enabled and the P wave rate is used in conjunction with an accelerometer based activity sensor for rate adaptive pacing. A VDDR pacemaker was implanted in three patients with complete AV block (mean age 63 +/- 1 year) and the mean implantation time was 29 minutes. Mean P wave amplitude was 2.4 mV (1.2-4.2 mV) at implantation and telemetered P wave amplitude was stable over a follow-up of 6 months. At a sensitivity of 0.2 mV, stable P wave sensing was observed during breathing maneuvers, arm swinging, myopotential induction, and Holter recording. Paired exercise tests performed in the VDDR and VVIR modes showed higher cardiac output at rest, during exercise, and in the recovery period in the VDDR pacing mode. Thus VDDR pacing using a single pass lead is superior to VVIR pacing by enabling P synchronous ventricular pacing without adding to the complexity of implantation.", "contents": "Initial clinical experience with a single pass VDDR pacing system. Although ventricular rate adaptive pacing (VVIR) improves exercise capacity and cardiac output compared to constant rate ventricular pacing (VVI), this pacing mode does not provide benefit of atrioventricular (AV) synchrony. We evaluated the use of a custom-built VDDR pacing system using a single pass, ventricular lead, which detects endocavity P wave using a pair of diagonally arranged atrial bipolar (DAB) electrodes. In the VDDR mode, AV synchrony is enabled and the P wave rate is used in conjunction with an accelerometer based activity sensor for rate adaptive pacing. A VDDR pacemaker was implanted in three patients with complete AV block (mean age 63 +/- 1 year) and the mean implantation time was 29 minutes. Mean P wave amplitude was 2.4 mV (1.2-4.2 mV) at implantation and telemetered P wave amplitude was stable over a follow-up of 6 months. At a sensitivity of 0.2 mV, stable P wave sensing was observed during breathing maneuvers, arm swinging, myopotential induction, and Holter recording. Paired exercise tests performed in the VDDR and VVIR modes showed higher cardiac output at rest, during exercise, and in the recovery period in the VDDR pacing mode. Thus VDDR pacing using a single pass lead is superior to VVIR pacing by enabling P synchronous ventricular pacing without adding to the complexity of implantation."} {"id": "PMID:1279568", "title": "Complications of single lead VDD pacing in 35 patients with AV block.", "content": "The implantation of a VDD system is comparable to that of a VVI system, but its management is associated with typical complications of dual chamber pacing. In 35 patients with symptomatic AV block and normal sinus node function, two different VDD pacing systems were implanted. Most of the complications described and their mode of resolution were common to VDD and DDD pacing; however, the VDD system eliminated the need for two separate leads. We, therefore, favor single lead VDD pacing in the treatment of complete AV block with normal sinus node function.", "contents": "Complications of single lead VDD pacing in 35 patients with AV block. The implantation of a VDD system is comparable to that of a VVI system, but its management is associated with typical complications of dual chamber pacing. In 35 patients with symptomatic AV block and normal sinus node function, two different VDD pacing systems were implanted. Most of the complications described and their mode of resolution were common to VDD and DDD pacing; however, the VDD system eliminated the need for two separate leads. We, therefore, favor single lead VDD pacing in the treatment of complete AV block with normal sinus node function."} {"id": "PMID:1279569", "title": "VDD single pass lead pacing: sustained pacemaker mediated tachycardias unrelated to retrograde atrial activation.", "content": "Pacemaker mediated tachycardias (PMTs) are a well known complication of P synchronous pacing. Although the initiating mechanisms are several, all of them are associated with retrograde atrial activation, which is sensed by the atrial sensing channel, resulting in ventricular pacing. In 19 patients suffering from symptomatic AV conduction disturbances and normal sinus node function, a VDD pacing system connected to a single pass ventricular lead with dual chamber electrodes was implanted. The bipolar atrial electrode, floating in the right atrium, was used to detect endocardial atrial electrograms that were differentially processed within the pacemaker for optimal discrimination and filtering of undesirable signals. The widely programmable atrial sensitivity (amplitude and filtering) allowed stable P synchronized ventricular pacing in all patients, but in five of them, sustained PMTs not related to retrograde atrial activation was documented during the follow-up. The common mechanism for the onset and maintenance of these PMTs was traced to the abnormal sensing of the terminal forces of ventricular activation and/or of the T wave. The possibility of interferences between ventricular and atrial electrodes (crosstalk) was also considered. The reduction of atrial channel sensitivity represented in all cases the only effective procedure to prevent this type of PMT. In conclusion, the bet signal to noise ratio is an important endpoint to assure the proper function of a single lead VDD pacing system. Furthermore, using the differential amplifier built within the pacemaker, consideration should be given to the optimal mode of rejection of the terminal forces of the QRS and T wave.", "contents": "VDD single pass lead pacing: sustained pacemaker mediated tachycardias unrelated to retrograde atrial activation. Pacemaker mediated tachycardias (PMTs) are a well known complication of P synchronous pacing. Although the initiating mechanisms are several, all of them are associated with retrograde atrial activation, which is sensed by the atrial sensing channel, resulting in ventricular pacing. In 19 patients suffering from symptomatic AV conduction disturbances and normal sinus node function, a VDD pacing system connected to a single pass ventricular lead with dual chamber electrodes was implanted. The bipolar atrial electrode, floating in the right atrium, was used to detect endocardial atrial electrograms that were differentially processed within the pacemaker for optimal discrimination and filtering of undesirable signals. The widely programmable atrial sensitivity (amplitude and filtering) allowed stable P synchronized ventricular pacing in all patients, but in five of them, sustained PMTs not related to retrograde atrial activation was documented during the follow-up. The common mechanism for the onset and maintenance of these PMTs was traced to the abnormal sensing of the terminal forces of ventricular activation and/or of the T wave. The possibility of interferences between ventricular and atrial electrodes (crosstalk) was also considered. The reduction of atrial channel sensitivity represented in all cases the only effective procedure to prevent this type of PMT. In conclusion, the bet signal to noise ratio is an important endpoint to assure the proper function of a single lead VDD pacing system. Furthermore, using the differential amplifier built within the pacemaker, consideration should be given to the optimal mode of rejection of the terminal forces of the QRS and T wave."} {"id": "PMID:1279570", "title": "Evaluation by cardiopulmonary exercise test of DDDR versus DDD pacing.", "content": "In eight patients (age 62 +/- 6 years) a DDDR pacemaker was implanted for sick sinus syndrome (three cases) or second- and third-degree AV block (five cases). In five subjects chronotropic incompetence (maximal heart rate on effort < 110 beats/min) was present before implantation. One month after implantation the patients were randomized to DDDR or DDD pacing for 3 weeks each, with subsequent crossover, and at the end of each period a symptom limited cardiopulmonary exercise test (25 watts/2 min) was performed and the patients were requested to fill a symptoms questionnaire. DDDR pacing, compared to DDD, was associated with higher maximal heart rates (127 +/- 20 vs 110 +/- 27 beats/min, P < 0.02), higher [VO2 max (25.4 +/- 6.1 vs 21.5 +/- 7.8 mL/kg/per min, P < 0.03) and higher VO2 at the anaerobic threshold (20.3 +/- 5.0 vs 15.8 +/- 4.9 mL/kg per min, P < 0.03), without significant differences in mean exercise time (526 +/- 193 vs 472 +/- 216 sec, NS). The increase in VO2 max obtained in DDDR versus DDD was significantly related to the increase in maximal heart rate (r = 0.72, P < 0.05) and the increase in VO2 at the anaerobic threshold obtained in DDDR versus DDD was related to the increase in heart rate at the anaerobic threshold (r = 0.81, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Evaluation by cardiopulmonary exercise test of DDDR versus DDD pacing. In eight patients (age 62 +/- 6 years) a DDDR pacemaker was implanted for sick sinus syndrome (three cases) or second- and third-degree AV block (five cases). In five subjects chronotropic incompetence (maximal heart rate on effort < 110 beats/min) was present before implantation. One month after implantation the patients were randomized to DDDR or DDD pacing for 3 weeks each, with subsequent crossover, and at the end of each period a symptom limited cardiopulmonary exercise test (25 watts/2 min) was performed and the patients were requested to fill a symptoms questionnaire. DDDR pacing, compared to DDD, was associated with higher maximal heart rates (127 +/- 20 vs 110 +/- 27 beats/min, P < 0.02), higher [VO2 max (25.4 +/- 6.1 vs 21.5 +/- 7.8 mL/kg/per min, P < 0.03) and higher VO2 at the anaerobic threshold (20.3 +/- 5.0 vs 15.8 +/- 4.9 mL/kg per min, P < 0.03), without significant differences in mean exercise time (526 +/- 193 vs 472 +/- 216 sec, NS). The increase in VO2 max obtained in DDDR versus DDD was significantly related to the increase in maximal heart rate (r = 0.72, P < 0.05) and the increase in VO2 at the anaerobic threshold obtained in DDDR versus DDD was related to the increase in heart rate at the anaerobic threshold (r = 0.81, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279571", "title": "Aerobic capacity in rate modulated pacing.", "content": "Whether heart rate or AV synchrony is the most important factor for an increase in aerobic capacity was evaluated in a comparative study between sinus bradycardia, VVIR, DDD, and DDDR stimulation. Sixteen patients (mean age 67 years) with chronotropic incompetence and implanted DDDR pacemaker (Telectronics META 1250) were randomly studied by cardiopulmonary exercise testing. All patients were exercised to their anaerobic threshold (AT) with the following heart rates: DDD 84 +/- 3, VVIR 110 +/- 5, and DDDR 116 +/- 6 beats/min. Mean oxygen uptake (VO2, mL/kg per min) at AT was 7.4 +/- 0.3 in DDD and VVIR modes. A 12% increase was measured in DDDR mode (8.3 +/- 0.4). Compared to VVIR work capacity in the DDDR mode was improved by 17% (41 vs 48 W/min). In patients with isolated sinus node disease (n = 9) the increase of VO2 and work capacity at AT during DDDR mode was more pronounced (16% and 20%, respectively, compared to VVIR). In patients with intermittent second or third degree AV block (n = 7) the differences between the pacing modes were not significant. This might partly be due to a lesser degree of chronotropic incompetence in this subgroup. In conclusion only the conjunction of heart rate increase and preservation of AV synchrony provides a significant improvement in aerobic capacity during exercise.", "contents": "Aerobic capacity in rate modulated pacing. Whether heart rate or AV synchrony is the most important factor for an increase in aerobic capacity was evaluated in a comparative study between sinus bradycardia, VVIR, DDD, and DDDR stimulation. Sixteen patients (mean age 67 years) with chronotropic incompetence and implanted DDDR pacemaker (Telectronics META 1250) were randomly studied by cardiopulmonary exercise testing. All patients were exercised to their anaerobic threshold (AT) with the following heart rates: DDD 84 +/- 3, VVIR 110 +/- 5, and DDDR 116 +/- 6 beats/min. Mean oxygen uptake (VO2, mL/kg per min) at AT was 7.4 +/- 0.3 in DDD and VVIR modes. A 12% increase was measured in DDDR mode (8.3 +/- 0.4). Compared to VVIR work capacity in the DDDR mode was improved by 17% (41 vs 48 W/min). In patients with isolated sinus node disease (n = 9) the increase of VO2 and work capacity at AT during DDDR mode was more pronounced (16% and 20%, respectively, compared to VVIR). In patients with intermittent second or third degree AV block (n = 7) the differences between the pacing modes were not significant. This might partly be due to a lesser degree of chronotropic incompetence in this subgroup. In conclusion only the conjunction of heart rate increase and preservation of AV synchrony provides a significant improvement in aerobic capacity during exercise."} {"id": "PMID:1279572", "title": "Comparison of intrinsic versus paced ventricular function.", "content": "There is increasing evidence supporting the benefits of providing optimum AV delay in cardiac pacing, though controversy exists regarding its value and the benefits of intrinsic versus paced ventricular activation. This study compared various AV delays at rest in patients whose native AV delays were > or = 200 msec. Only patients with DDD pacemakers who had intact AV conduction and normal ventricular activation were included in the study. Nine patients were studied. Ten studies were performed. Evaluation was done in AAI and DDD modes at paced heart rates of 60/min or as close as possible to the intrinsic heart rate if this was > 60/min. Stroke volume (SV) and cardiac output (CO) were measured. When AV sequential pacing in the DDD mode with an optimum AV delay was compared to AAI pacing with a prolonged AV interval, the average optimum AV delay in the DDD mode was 157 msec and ranged from 125 to 175 msec. The average AV interval in the AAI mode was 245 msec and ranged from 212 to 300 msec. In the DDD mode, there was an overall significant improvement in CO of 11% and SV of 9%. Patients with intrinsic AV conduction times of > 220 msec showed an overall significant improvement in CO of 13% and SV of 11%. In patients with intrinsic AV conduction times of < 220 msec, an improvement in CO of 6% and SV of 4% was seen. (1) An optimum AV delay is an important component of hemodynamic performance; and (2) AV sequential pacing at rest with an optimum AV delay may provide better hemodynamic performance than atrial pacing with intrinsic ventricular conduction when native AV conduction is prolonged > 220 msec.", "contents": "Comparison of intrinsic versus paced ventricular function. There is increasing evidence supporting the benefits of providing optimum AV delay in cardiac pacing, though controversy exists regarding its value and the benefits of intrinsic versus paced ventricular activation. This study compared various AV delays at rest in patients whose native AV delays were > or = 200 msec. Only patients with DDD pacemakers who had intact AV conduction and normal ventricular activation were included in the study. Nine patients were studied. Ten studies were performed. Evaluation was done in AAI and DDD modes at paced heart rates of 60/min or as close as possible to the intrinsic heart rate if this was > 60/min. Stroke volume (SV) and cardiac output (CO) were measured. When AV sequential pacing in the DDD mode with an optimum AV delay was compared to AAI pacing with a prolonged AV interval, the average optimum AV delay in the DDD mode was 157 msec and ranged from 125 to 175 msec. The average AV interval in the AAI mode was 245 msec and ranged from 212 to 300 msec. In the DDD mode, there was an overall significant improvement in CO of 11% and SV of 9%. Patients with intrinsic AV conduction times of > 220 msec showed an overall significant improvement in CO of 13% and SV of 11%. In patients with intrinsic AV conduction times of < 220 msec, an improvement in CO of 6% and SV of 4% was seen. (1) An optimum AV delay is an important component of hemodynamic performance; and (2) AV sequential pacing at rest with an optimum AV delay may provide better hemodynamic performance than atrial pacing with intrinsic ventricular conduction when native AV conduction is prolonged > 220 msec."} {"id": "PMID:1279573", "title": "Precision of impedance cardiography measurements of cardiac output in pacemaker patients.", "content": "Objective hemodynamic assessment of pacemaker patients is necessary for gauging responses to changes in programming or other conditions that affect the circulation. Impedance cardiography permits noninvasive, repetitive determinations of cardiac output at short intervals, but data regarding variability of this method in patients with pacemakers is unavailable. Thirty-eight patients with implanted pacemakers (24 DDD, 14 VVI) and six normal subjects were studied. A computerized impedance cardiograph was used to calculate cardiac output from the product of the first derivative of the thoracic impedance signal (dZ/dt), the ventricular ejection time, and heart rate. Each patient was studied while supine after a period of at least 15 minutes of rest and repeated impedance measurements (about ten) were performed. Fourteen patients were studied in sinus rhythm, 24 were studied during DDD pacing, and 32 patients were studied during VVI pacing. Cardiac and stroke indices were calculated 706 times on the basis of 11,296 accepted beats. Variability was assessed by methods that analyzed serial measurements and variability between two consecutive and nonconsecutive measurements. The mean indices and coefficients of variation of two measurements and of serial measurements in sinus rhythm and during DDD pacing were 4%; in VVI it was 6%. The precision of impedance cardiography in all pacing modes, as demonstrated by analysis of variability, indicates that detected changes of stroke volume and cardiac output > 7% on serial (two and more) measurements, performed by the same operator and during the same session, represent true hemodynamic alterations with 95% confidence.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Precision of impedance cardiography measurements of cardiac output in pacemaker patients. Objective hemodynamic assessment of pacemaker patients is necessary for gauging responses to changes in programming or other conditions that affect the circulation. Impedance cardiography permits noninvasive, repetitive determinations of cardiac output at short intervals, but data regarding variability of this method in patients with pacemakers is unavailable. Thirty-eight patients with implanted pacemakers (24 DDD, 14 VVI) and six normal subjects were studied. A computerized impedance cardiograph was used to calculate cardiac output from the product of the first derivative of the thoracic impedance signal (dZ/dt), the ventricular ejection time, and heart rate. Each patient was studied while supine after a period of at least 15 minutes of rest and repeated impedance measurements (about ten) were performed. Fourteen patients were studied in sinus rhythm, 24 were studied during DDD pacing, and 32 patients were studied during VVI pacing. Cardiac and stroke indices were calculated 706 times on the basis of 11,296 accepted beats. Variability was assessed by methods that analyzed serial measurements and variability between two consecutive and nonconsecutive measurements. The mean indices and coefficients of variation of two measurements and of serial measurements in sinus rhythm and during DDD pacing were 4%; in VVI it was 6%. The precision of impedance cardiography in all pacing modes, as demonstrated by analysis of variability, indicates that detected changes of stroke volume and cardiac output > 7% on serial (two and more) measurements, performed by the same operator and during the same session, represent true hemodynamic alterations with 95% confidence.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279574", "title": "Diastolic mitral regurgitation in patients with first-degree atrioventricular block.", "content": "Diastolic mitral regurgitation has been observed in patients with DDD pacemakers when the atrioventricular (AV) delay was prolonged. However, diastolic mitral regurgitation associated with first-degree AV block has not been fully studied. We examined transmitral blood flow in 24 patients with first-degree AV block and normal cardiac function (ages 35.3 +/- 17.4 years), and in nine patients with DDD pacemakers and normal cardiac function (ages 73.1 +/- 8.1 years), using pulsed Doppler echocardiography. Diastolic mitral regurgitation was observed in 19 of 24 patients with first-degree AV block. Although PQ interval was shortened from 0.32 +/- 0.06 to 0.20 +/- 0.05 seconds (P < 0.01) after 1 mg atropine sulfate IV, the interval between P wave (ECG) and the beginning of diastolic mitral regurgitation did not change, while the duration of diastolic mitral regurgitation was shortened from 0.15 +/- 0.03 to 0.05 +/- 0.03 seconds (P < 0.01). There was a significant correlation between changes in PQ interval and changes in the duration of diastolic mitral regurgitation (r = 0.92, P < 0.001). Although cardiac output (3.9 +/- 0.05 L/min) and pulmonary capillary wedge pressure (5.1 +/- 1.5 mmHg) were normal in all patients with pacemakers, diastolic mitral regurgitation was observed when the AV delay was prolonged. The critical PQ interval for the appearance of diastolic mitral regurgitation was 0.23 +/- 0.01 seconds. In patients with prolonged PQ intervals, delayed ventricular contraction following atrial contraction may be associated with mitral regurgitation in the presence of a reversed AV pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Diastolic mitral regurgitation in patients with first-degree atrioventricular block. Diastolic mitral regurgitation has been observed in patients with DDD pacemakers when the atrioventricular (AV) delay was prolonged. However, diastolic mitral regurgitation associated with first-degree AV block has not been fully studied. We examined transmitral blood flow in 24 patients with first-degree AV block and normal cardiac function (ages 35.3 +/- 17.4 years), and in nine patients with DDD pacemakers and normal cardiac function (ages 73.1 +/- 8.1 years), using pulsed Doppler echocardiography. Diastolic mitral regurgitation was observed in 19 of 24 patients with first-degree AV block. Although PQ interval was shortened from 0.32 +/- 0.06 to 0.20 +/- 0.05 seconds (P < 0.01) after 1 mg atropine sulfate IV, the interval between P wave (ECG) and the beginning of diastolic mitral regurgitation did not change, while the duration of diastolic mitral regurgitation was shortened from 0.15 +/- 0.03 to 0.05 +/- 0.03 seconds (P < 0.01). There was a significant correlation between changes in PQ interval and changes in the duration of diastolic mitral regurgitation (r = 0.92, P < 0.001). Although cardiac output (3.9 +/- 0.05 L/min) and pulmonary capillary wedge pressure (5.1 +/- 1.5 mmHg) were normal in all patients with pacemakers, diastolic mitral regurgitation was observed when the AV delay was prolonged. The critical PQ interval for the appearance of diastolic mitral regurgitation was 0.23 +/- 0.01 seconds. In patients with prolonged PQ intervals, delayed ventricular contraction following atrial contraction may be associated with mitral regurgitation in the presence of a reversed AV pressure gradient.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279575", "title": "Orthostatic responses in patients with DDD pacemakers: signs of autonomic dysfunction.", "content": "Responses to orthostasis may be altered in states associated with autonomic dysfunction. Computerized impedance cardiography, a noninvasive method for continuous assessment of stroke volume and mean blood pressure, was utilized to study the postural hemodynamic changes in eight normal and 27 patients with DDD pacemakers. Twenty patients with complete heart block (five with heart failure) were studied in the VDD mode and seven patients with sick sinus syndrome were assessed in DVI (four) or VDD (three). The results with pacemaker patients are significantly different from those observed in normal. Pacemaker patient responses to standing included: (1) a reduction in systolic, diastolic, and mean blood pressure; (2) an increase in heart rate in patients with intact sinus node function and no change in patients with sick sinus syndrome; and (3) stroke volume was unchanged in patients with sick sinus syndrome or heart failure and only modest reduction occurred in the remaining patients. (1) No reduction in stroke volume during upright posture occurs in DDD patients with sick sinus syndrome and this appears to be a compensatory reaction to an inadequate heart rate response to standing; (2) The hemodynamic response of DDD patients to the assumption of an upright posture is consistent with autonomic dysfunction; and (3) The primary cause for autonomic dysfunction in DDD patients may be the asynchronous ventricular depolarization caused by right ventricular pacing.", "contents": "Orthostatic responses in patients with DDD pacemakers: signs of autonomic dysfunction. Responses to orthostasis may be altered in states associated with autonomic dysfunction. Computerized impedance cardiography, a noninvasive method for continuous assessment of stroke volume and mean blood pressure, was utilized to study the postural hemodynamic changes in eight normal and 27 patients with DDD pacemakers. Twenty patients with complete heart block (five with heart failure) were studied in the VDD mode and seven patients with sick sinus syndrome were assessed in DVI (four) or VDD (three). The results with pacemaker patients are significantly different from those observed in normal. Pacemaker patient responses to standing included: (1) a reduction in systolic, diastolic, and mean blood pressure; (2) an increase in heart rate in patients with intact sinus node function and no change in patients with sick sinus syndrome; and (3) stroke volume was unchanged in patients with sick sinus syndrome or heart failure and only modest reduction occurred in the remaining patients. (1) No reduction in stroke volume during upright posture occurs in DDD patients with sick sinus syndrome and this appears to be a compensatory reaction to an inadequate heart rate response to standing; (2) The hemodynamic response of DDD patients to the assumption of an upright posture is consistent with autonomic dysfunction; and (3) The primary cause for autonomic dysfunction in DDD patients may be the asynchronous ventricular depolarization caused by right ventricular pacing."} {"id": "PMID:1279576", "title": "Noninvasive transcutaneous cardiac pacing: modern instrumentation and new perspectives.", "content": "Noninvasive transcutaneous cardiac pacing has evolved from a simple stand alone unit with no ventricular sensing to a complete cardiac arrest resuscitation system combining synchronous pacing and defibrillation capabilities and using a single set of multifunction electrodes. In current instrumentation, four configurations exist including stand alone unit, modular configuration, built-in monitor and recorder, and built-in monitor, recorder and defibrillator. In present day devices, ventricular sensing, extensive programmability, and large surface electrodes are general features. Capture monitoring requires specific integrated electrocardiographic capability. Future developments are expected to involve low threshold electrode technology, integrated mechanical monitoring, and interdevice electrode compatibility.", "contents": "Noninvasive transcutaneous cardiac pacing: modern instrumentation and new perspectives. Noninvasive transcutaneous cardiac pacing has evolved from a simple stand alone unit with no ventricular sensing to a complete cardiac arrest resuscitation system combining synchronous pacing and defibrillation capabilities and using a single set of multifunction electrodes. In current instrumentation, four configurations exist including stand alone unit, modular configuration, built-in monitor and recorder, and built-in monitor, recorder and defibrillator. In present day devices, ventricular sensing, extensive programmability, and large surface electrodes are general features. Capture monitoring requires specific integrated electrocardiographic capability. Future developments are expected to involve low threshold electrode technology, integrated mechanical monitoring, and interdevice electrode compatibility."} {"id": "PMID:1279577", "title": "Observations on induction and termination of paroxysmal supraventricular tachycardia by external pacing.", "content": "Paroxysmal supraventricular tachycardia (PSVT) can be reproducibly induced and terminated by critically timed atrial or ventricular depolarizations. In this study, noninvasive transcutaneous (external) cardiac pacing (NTCP) was compared to endocardial ventricular pacing for the termination and induction of PSVT. In 24 patients, either atrioventricular (AV) nodal reentrant tachycardia or AV reciprocating tachycardia was reproducibly terminated with either critically timed ventricular depolarizations or overdrive ventricular pacing from an endocardial right ventricular site. There were 32 trials of NTCP attempts to interrupt PSVT in the 24 patients. External pacing was successful at terminating PSVT in 23 patients and in 30 of 32 (94%) trials. In 20 patients, there were 26 trials of external pacing attempts to induce PSVT. External pacing initiated PSVT in 21 of 26 trials (81%). The pacing sequences used to induce and terminate PSVT with external pacing were copied from the endocardial sequences. The external pacing threshold averaged 77 +/- 22 mA but the current needed to terminate PSVT was about 1.5 greater than threshold at 117 +/- 27 mA. Serial external pacing studies were performed in seven patients. The thresholds for external pacing were similar from trial to trial as were the mode of termination and induction between the endocardial and external methods. External pacing can terminate most AV reciprocating tachycardias and many AV nodal reentrant tachycardias. It appears promising as a means of inducing PSVT. However, the high stimulation amplitudes needed will prohibit wide acceptance of external pacing for induction and termination of PSVT.", "contents": "Observations on induction and termination of paroxysmal supraventricular tachycardia by external pacing. Paroxysmal supraventricular tachycardia (PSVT) can be reproducibly induced and terminated by critically timed atrial or ventricular depolarizations. In this study, noninvasive transcutaneous (external) cardiac pacing (NTCP) was compared to endocardial ventricular pacing for the termination and induction of PSVT. In 24 patients, either atrioventricular (AV) nodal reentrant tachycardia or AV reciprocating tachycardia was reproducibly terminated with either critically timed ventricular depolarizations or overdrive ventricular pacing from an endocardial right ventricular site. There were 32 trials of NTCP attempts to interrupt PSVT in the 24 patients. External pacing was successful at terminating PSVT in 23 patients and in 30 of 32 (94%) trials. In 20 patients, there were 26 trials of external pacing attempts to induce PSVT. External pacing initiated PSVT in 21 of 26 trials (81%). The pacing sequences used to induce and terminate PSVT with external pacing were copied from the endocardial sequences. The external pacing threshold averaged 77 +/- 22 mA but the current needed to terminate PSVT was about 1.5 greater than threshold at 117 +/- 27 mA. Serial external pacing studies were performed in seven patients. The thresholds for external pacing were similar from trial to trial as were the mode of termination and induction between the endocardial and external methods. External pacing can terminate most AV reciprocating tachycardias and many AV nodal reentrant tachycardias. It appears promising as a means of inducing PSVT. However, the high stimulation amplitudes needed will prohibit wide acceptance of external pacing for induction and termination of PSVT."} {"id": "PMID:1279578", "title": "Balloon electrode catheter for transesophageal atrial pacing and transesophageal ECG recording.", "content": "A new balloon electrode catheter (10 French) with five or six balloon electrodes placed on the cardiac side was developed for transesophageal atrial pacing and bipolar ECG recording. The diameter of the hemispheric electrodes is 6 mm and the length of the esophageal balloon is 10 cm. The transesophageal atrial pacing threshold was measured with the balloon electrode catheter by transesophageal programmed atrial stimulation (TPS) (n = 54). At the onset of TPS, the feeling, capture (n = 54), and pain voltage threshold (n = 6) were measured by increasing the amplitude of the pacing voltage during high rate bipolar atrial pacing and bipolar atrial ECG recording. In 38 TPS, the capture threshold was lower than the feeling threshold (n = 28). In 16 TPS, the capture threshold was higher than the feeling threshold. In conclusion, painless atrial pacing and excellent ECG recording can be achieved with a multipolar esophageal balloon electrode catheter with a low pacing voltage amplitude and a high P wave amplitude.", "contents": "Balloon electrode catheter for transesophageal atrial pacing and transesophageal ECG recording. A new balloon electrode catheter (10 French) with five or six balloon electrodes placed on the cardiac side was developed for transesophageal atrial pacing and bipolar ECG recording. The diameter of the hemispheric electrodes is 6 mm and the length of the esophageal balloon is 10 cm. The transesophageal atrial pacing threshold was measured with the balloon electrode catheter by transesophageal programmed atrial stimulation (TPS) (n = 54). At the onset of TPS, the feeling, capture (n = 54), and pain voltage threshold (n = 6) were measured by increasing the amplitude of the pacing voltage during high rate bipolar atrial pacing and bipolar atrial ECG recording. In 38 TPS, the capture threshold was lower than the feeling threshold (n = 28). In 16 TPS, the capture threshold was higher than the feeling threshold. In conclusion, painless atrial pacing and excellent ECG recording can be achieved with a multipolar esophageal balloon electrode catheter with a low pacing voltage amplitude and a high P wave amplitude."} {"id": "PMID:1279579", "title": "Prediction of permanent atrial sensing by preoperative esophageal atrial wave evaluation.", "content": "Atrial undersensing is a common problem in permanent atrial and dual chamber pacing. The purpose of this study was to evaluate the relationship between transesophageal atrial wave (EsAW) and right atrial endocavitary (RA). Forty-seven patients 72 +/- 9.7 years of age, with symptomatic bradyarrhythmias were studied. The EsAW was filtered with a high pass filter of 10 Hz (Arzco preamplifier-filter), using 1, 2, and 3 cm bipolar transesophageal catheters. Atrial bipolar floating 1, 2, and 3 cm electrograms from the high RA (HRA) and from the mid RA (MRA), as well as unipolar electrograms from the right auricle (RAUR) were recorded 1 day later. Comparison by paired t-test showed no significant differences between EsAW and bipolar sensing in RA, but significant differences between EsAW and RAUR (P = 0.0001). The results of the Spearman correlation coefficient for sensing (mV) for EsAW, HRA, and MRA, respectively, were: 1 cm, 1.8 +/- 0.9, 1.7 +/- 0.9, and 1.9 +/- 0.9 (z > 3.5; P < 0.0003); 2 cm, 2.2 +/- 0.9, 1.9 +/- 0.8, and 2.1 +/- 0.9 (z > 2.3; P < 0.03); 3 cm, 2.1 +/- 1, 2 +/- 0.9, and 2.2 +/- 1.0 (z > 2.9; P < 0.003); and the result for the monopolar RAUR was 3.0 +/- 1.0 (z < 1.4; P > 0.17). These findings, if confirmed in more patients, indicate that preoperative EsAW recording could be useful in estimating the quality of bipolar floating electrograms from the RA but not of unipolar RAUR.", "contents": "Prediction of permanent atrial sensing by preoperative esophageal atrial wave evaluation. Atrial undersensing is a common problem in permanent atrial and dual chamber pacing. The purpose of this study was to evaluate the relationship between transesophageal atrial wave (EsAW) and right atrial endocavitary (RA). Forty-seven patients 72 +/- 9.7 years of age, with symptomatic bradyarrhythmias were studied. The EsAW was filtered with a high pass filter of 10 Hz (Arzco preamplifier-filter), using 1, 2, and 3 cm bipolar transesophageal catheters. Atrial bipolar floating 1, 2, and 3 cm electrograms from the high RA (HRA) and from the mid RA (MRA), as well as unipolar electrograms from the right auricle (RAUR) were recorded 1 day later. Comparison by paired t-test showed no significant differences between EsAW and bipolar sensing in RA, but significant differences between EsAW and RAUR (P = 0.0001). The results of the Spearman correlation coefficient for sensing (mV) for EsAW, HRA, and MRA, respectively, were: 1 cm, 1.8 +/- 0.9, 1.7 +/- 0.9, and 1.9 +/- 0.9 (z > 3.5; P < 0.0003); 2 cm, 2.2 +/- 0.9, 1.9 +/- 0.8, and 2.1 +/- 0.9 (z > 2.3; P < 0.03); 3 cm, 2.1 +/- 1, 2 +/- 0.9, and 2.2 +/- 1.0 (z > 2.9; P < 0.003); and the result for the monopolar RAUR was 3.0 +/- 1.0 (z < 1.4; P > 0.17). These findings, if confirmed in more patients, indicate that preoperative EsAW recording could be useful in estimating the quality of bipolar floating electrograms from the RA but not of unipolar RAUR."} {"id": "PMID:1279580", "title": "Termination of tachycardias by transesophageal electrical pacing.", "content": "To evaluate the therapeutic significance of noninvasive transesophageal pacing for termination of tachycardias the method of rapid atrial or ventricular transesophageal pacing was used in 233 patients with different tachycardiac arrhythmias. We were able to terminate atrial flutter in 136 of 162 patients by transesophageal rapid atrial stimulation (conversion to sinus rhythm in 75 cases, induction of atrial fibrillation in 61 cases). Atrial tachycardias were interrupted in 17 of 23 patients (sinus rhythm in 11 cases, atrial fibrillation in six cases). AV reciprocating/AV nodal supraventricular reentry tachycardias were terminated in 62 of 63 patients (sinus rhythm in 58 cases, atrial fibrillation in four cases). By transesophageal rapid ventricular pacing ventricular tachycardias could be terminated in ten of 15 patients. The success rate of transesophageal pacing was influenced by the pacing rate, by the type of tachycardiac arrhythmia inclusive by the type of atrial flutter and by the tachycardia's cycle length. Because the success rates are comparable with invasive technique and the procedure is simpler, the noninvasive transesophageal antitachycardiac pacing should be respected as the method of the first choice in patients with supraventricular tachycardias.", "contents": "Termination of tachycardias by transesophageal electrical pacing. To evaluate the therapeutic significance of noninvasive transesophageal pacing for termination of tachycardias the method of rapid atrial or ventricular transesophageal pacing was used in 233 patients with different tachycardiac arrhythmias. We were able to terminate atrial flutter in 136 of 162 patients by transesophageal rapid atrial stimulation (conversion to sinus rhythm in 75 cases, induction of atrial fibrillation in 61 cases). Atrial tachycardias were interrupted in 17 of 23 patients (sinus rhythm in 11 cases, atrial fibrillation in six cases). AV reciprocating/AV nodal supraventricular reentry tachycardias were terminated in 62 of 63 patients (sinus rhythm in 58 cases, atrial fibrillation in four cases). By transesophageal rapid ventricular pacing ventricular tachycardias could be terminated in ten of 15 patients. The success rate of transesophageal pacing was influenced by the pacing rate, by the type of tachycardiac arrhythmia inclusive by the type of atrial flutter and by the tachycardia's cycle length. Because the success rates are comparable with invasive technique and the procedure is simpler, the noninvasive transesophageal antitachycardiac pacing should be respected as the method of the first choice in patients with supraventricular tachycardias."} {"id": "PMID:1279581", "title": "Is polyurethane lead insulation still controversial?", "content": "A controversy arose some 10 years ago over the reliability of polyurethane lead insulation. On the basis of one of the longest standing and largest databanks worldwide, the authors compare the cumulative survival of several thousand polyurethane, standard silastic, and high-performance silastic electrodes as it pertains to the failure criterion described as insulation degradation. With the possible exception of the Medtronic 6972 (Medtronic, Inc.) electrode, polyurethane electrodes have a 100% reliability at 84 months, which is similar to silastic electrodes.", "contents": "Is polyurethane lead insulation still controversial? A controversy arose some 10 years ago over the reliability of polyurethane lead insulation. On the basis of one of the longest standing and largest databanks worldwide, the authors compare the cumulative survival of several thousand polyurethane, standard silastic, and high-performance silastic electrodes as it pertains to the failure criterion described as insulation degradation. With the possible exception of the Medtronic 6972 (Medtronic, Inc.) electrode, polyurethane electrodes have a 100% reliability at 84 months, which is similar to silastic electrodes."} {"id": "PMID:1279582", "title": "Threshold and polarization properties of modern active fixation atrial leads.", "content": "The purpose of the study was to compare the stimulation characteristics of two modern active fixation leads (Ela 583F, vitreous carbon tip [ELA] and Intermedics 82-0008-1601, iridium oxide tip [IROX]) with a standard lead (Osypka KY 67 VC, carbon-covered elgiloy tip [OSY]). In three groups of ten patients each, minimum charge threshold delta Qmin and polarization properties were determined via charge telemetry of the pacemaker (Intermedics Cosmos II and Relay) 0, 2, 5, 10, 28, 90, and 180 days after implant (dai). The polarization parameters global capacitance Cg, global resistance Rg, polarization voltage U(p), and a time constant t* (t* = Cg.Rg) were obtained by nonlinear regression. U(p) was always significantly (sig) lower in ELA and IROX (0.04-0.10 V) compared to OSY (0.54-0.76 V). Rg was sig lower in ELA (330-437 omega) compared to OSY and IROX (414-588 omega) from 0 to 28 dai. From 2 to 10 dai, Cg was sig higher in ELA and IROX (3.8-4.2 microF) compared to OSY (3.3-3.4 microF). In the three groups, delta Qmin reached a comparable maximum (1-1.2 microC) at 5 dai. Therefore, vitreous carbon and iridium oxide atrial fixation leads exhibit low chronic polarization effects compared to a standard elgiloy lead, but do not show a sig reduction in charge threshold.", "contents": "Threshold and polarization properties of modern active fixation atrial leads. The purpose of the study was to compare the stimulation characteristics of two modern active fixation leads (Ela 583F, vitreous carbon tip [ELA] and Intermedics 82-0008-1601, iridium oxide tip [IROX]) with a standard lead (Osypka KY 67 VC, carbon-covered elgiloy tip [OSY]). In three groups of ten patients each, minimum charge threshold delta Qmin and polarization properties were determined via charge telemetry of the pacemaker (Intermedics Cosmos II and Relay) 0, 2, 5, 10, 28, 90, and 180 days after implant (dai). The polarization parameters global capacitance Cg, global resistance Rg, polarization voltage U(p), and a time constant t* (t* = Cg.Rg) were obtained by nonlinear regression. U(p) was always significantly (sig) lower in ELA and IROX (0.04-0.10 V) compared to OSY (0.54-0.76 V). Rg was sig lower in ELA (330-437 omega) compared to OSY and IROX (414-588 omega) from 0 to 28 dai. From 2 to 10 dai, Cg was sig higher in ELA and IROX (3.8-4.2 microF) compared to OSY (3.3-3.4 microF). In the three groups, delta Qmin reached a comparable maximum (1-1.2 microC) at 5 dai. Therefore, vitreous carbon and iridium oxide atrial fixation leads exhibit low chronic polarization effects compared to a standard elgiloy lead, but do not show a sig reduction in charge threshold."} {"id": "PMID:1279583", "title": "Atrial stimulation by means of floating electrodes: a multicenter experience. The Multicenter Study Group.", "content": "It is well established that single lead VDD pacing is a physiological, reliable, and easy to use mode of pacing. The major limitation of VDD pacing is the need of a normal sinus node function, confirming its indication to patients with isolated atrioventricular conduction disturbances. The Phymos 830 pacing lead was originally designed for VDD pacing in association with the Phymos MPS pulse generator; it has a floating atrial dipole with an interelectrode distance of 3 cm; the distal electrode is 11, 13, or 15 cm proximal to the tip. As a result of the incidental observation of atrial captures occurring at very low pulse amplitudes delivered from the floating dipole of this lead, a 13-center Italian study was initiated to test the systematic feasibility of this type of atrial pacing. Pacing parameters were set and strength-duration curves were acquired with the PSA Master 470 external device. The investigation was performed at pacemaker implant in 114 patients in the supine position. The tip of the electrode was positioned at the right ventricular apex and the atrial dipole at the site of the highest endocavitary signal. Atrial bipolar pacing was performed with the proximal electrode as the cathode. Stable atrial capture was obtained in 108 of 114 patients (94.7%); pacing threshold was < 3.5 V with a pulse width of 1 msec in 85 of 108 patients. Results of voltage threshold were: 2.99 +/- 1.25 and 2.59 +/- 1.13 V at pulse widths of 0.5 and 1 msec, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Atrial stimulation by means of floating electrodes: a multicenter experience. The Multicenter Study Group. It is well established that single lead VDD pacing is a physiological, reliable, and easy to use mode of pacing. The major limitation of VDD pacing is the need of a normal sinus node function, confirming its indication to patients with isolated atrioventricular conduction disturbances. The Phymos 830 pacing lead was originally designed for VDD pacing in association with the Phymos MPS pulse generator; it has a floating atrial dipole with an interelectrode distance of 3 cm; the distal electrode is 11, 13, or 15 cm proximal to the tip. As a result of the incidental observation of atrial captures occurring at very low pulse amplitudes delivered from the floating dipole of this lead, a 13-center Italian study was initiated to test the systematic feasibility of this type of atrial pacing. Pacing parameters were set and strength-duration curves were acquired with the PSA Master 470 external device. The investigation was performed at pacemaker implant in 114 patients in the supine position. The tip of the electrode was positioned at the right ventricular apex and the atrial dipole at the site of the highest endocavitary signal. Atrial bipolar pacing was performed with the proximal electrode as the cathode. Stable atrial capture was obtained in 108 of 114 patients (94.7%); pacing threshold was < 3.5 V with a pulse width of 1 msec in 85 of 108 patients. Results of voltage threshold were: 2.99 +/- 1.25 and 2.59 +/- 1.13 V at pulse widths of 0.5 and 1 msec, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279584", "title": "Evaluation of an in-line bipolar polyurethane ventricular pacing lead.", "content": "A study was undertaken to evaluate the performance of the Medtronic 4012 polyurethane in-line bipolar pacing electrode. One hundred twenty six patients implanted with the 4012 lead were followed by our clinic with 116 of these leads implanted at our institution. Patients were followed a minimum of every 4 months. Testing included the performance of stimulation thresholds, sensing thresholds, and provocative maneuvers to evaluate for myopotential inhibition testing a minimum of every eight months. There were 12 documented lead failures of the total 126 patients. Further analysis was limited to the ten failures occurring in the 116 leads implanted at our center. All ten failed leads utilized the suture anchoring sleeve. Six of the leads were left cephalic implants, three were right cephalic, and one was right subclavian. Manifestations of failure included: seven oversensing abnormalities, three undersensing, four loss of ventricular capture, one premature end of service, four lead impedance decreases to < 250 omega and some presentations in combination. No leads were explanted for evaluation. The Kaplan-Meier product limit method was used to estimate the time to lead failure. The probability of not experiencing a lead failure within the first 4 years of implant is estimated to be 0.9103 (SE = 0.0338). Pacemaker dependent patients implanted with the 4012 lead should be given special consideration for prophylactic replacement.", "contents": "Evaluation of an in-line bipolar polyurethane ventricular pacing lead. A study was undertaken to evaluate the performance of the Medtronic 4012 polyurethane in-line bipolar pacing electrode. One hundred twenty six patients implanted with the 4012 lead were followed by our clinic with 116 of these leads implanted at our institution. Patients were followed a minimum of every 4 months. Testing included the performance of stimulation thresholds, sensing thresholds, and provocative maneuvers to evaluate for myopotential inhibition testing a minimum of every eight months. There were 12 documented lead failures of the total 126 patients. Further analysis was limited to the ten failures occurring in the 116 leads implanted at our center. All ten failed leads utilized the suture anchoring sleeve. Six of the leads were left cephalic implants, three were right cephalic, and one was right subclavian. Manifestations of failure included: seven oversensing abnormalities, three undersensing, four loss of ventricular capture, one premature end of service, four lead impedance decreases to < 250 omega and some presentations in combination. No leads were explanted for evaluation. The Kaplan-Meier product limit method was used to estimate the time to lead failure. The probability of not experiencing a lead failure within the first 4 years of implant is estimated to be 0.9103 (SE = 0.0338). Pacemaker dependent patients implanted with the 4012 lead should be given special consideration for prophylactic replacement."} {"id": "PMID:1279585", "title": "Thin bipolar leads: a solution to problems with coaxial bipolar designs.", "content": "A new type of bipolar lead has been designed to be thinner and more reliable than the standard coaxial design. The new lead has passed numerous bench tests to ensure its reliability. Improved fatigue performance was shown during comparisons between the new type of coil (bifilar DFT [drawn filled tube]) and previous standard coils (trifilar MP35N). During the initial animal studies no reliability concerns were raised and stable electrode thresholds were measured. If success in the test process of this lead continues, a bipolar lead may soon be marketed with a size and reliability comparable to unipolar leads.", "contents": "Thin bipolar leads: a solution to problems with coaxial bipolar designs. A new type of bipolar lead has been designed to be thinner and more reliable than the standard coaxial design. The new lead has passed numerous bench tests to ensure its reliability. Improved fatigue performance was shown during comparisons between the new type of coil (bifilar DFT [drawn filled tube]) and previous standard coils (trifilar MP35N). During the initial animal studies no reliability concerns were raised and stable electrode thresholds were measured. If success in the test process of this lead continues, a bipolar lead may soon be marketed with a size and reliability comparable to unipolar leads."} {"id": "PMID:1279586", "title": "Pacing lead survival: performance of different models.", "content": "Recent reports have shown poor survival of some leads currently in use. Long-term survival analysis of 2,444 leads (1,059 atrial and 1,385 ventricular) implanted in this institution since January 1980, and having at least 1 month of follow-up was performed. The survival of 123 different models was compared with the average survival of all the leads implanted in the corresponding chamber. Failure was defined as inactivation of the lead (electrical abandonment, explant, or cap) due to insulator and/or conductor fracture. The mean follow-up was 33 +/- 32 months. The cumulative survival for different atrial lead models was consistent with the average performance in the atrium. No atrial lead showed better or worse survival compared to the others. In the ventricular group, the Medtronic 4012 lead showed statistically significant poorer survival (P = 0.01) compared with the average survival of the ventricular leads. The Cardiac Pacemakers, Inc. (CPI) 4010 lead showed a nonsignificant (P = 0.12) worse performance than the average for ventricular leads. (1) The Medtronic 4012 had a significantly poorer performance than the rest of the leads. A trend in similar direction was found for the CPI 4010, also in the ventricular group; (2) Atrial lead models showed a stable survival; and (3) Frequent follow-up is required for some leads, especially in pacemaker dependent patients.", "contents": "Pacing lead survival: performance of different models. Recent reports have shown poor survival of some leads currently in use. Long-term survival analysis of 2,444 leads (1,059 atrial and 1,385 ventricular) implanted in this institution since January 1980, and having at least 1 month of follow-up was performed. The survival of 123 different models was compared with the average survival of all the leads implanted in the corresponding chamber. Failure was defined as inactivation of the lead (electrical abandonment, explant, or cap) due to insulator and/or conductor fracture. The mean follow-up was 33 +/- 32 months. The cumulative survival for different atrial lead models was consistent with the average performance in the atrium. No atrial lead showed better or worse survival compared to the others. In the ventricular group, the Medtronic 4012 lead showed statistically significant poorer survival (P = 0.01) compared with the average survival of the ventricular leads. The Cardiac Pacemakers, Inc. (CPI) 4010 lead showed a nonsignificant (P = 0.12) worse performance than the average for ventricular leads. (1) The Medtronic 4012 had a significantly poorer performance than the rest of the leads. A trend in similar direction was found for the CPI 4010, also in the ventricular group; (2) Atrial lead models showed a stable survival; and (3) Frequent follow-up is required for some leads, especially in pacemaker dependent patients."} {"id": "PMID:1279587", "title": "The measurement of the paced depolarization integral using the braided endocardial lead.", "content": "Previous studies have shown that the paced depolarization integral (PDI) data recorded in unipolar configuration could potentially improve the specificity of tachyarrhythmia classification in an implantable cardioverter defibrillator (ICD). However, the defibrillation protection would be compromised if the ICD case were used as an indifferent electrode. Since transvenous defibrillation leads are being investigated to be used with ICDs, this study determined if reliable PDI data could be obtained using the braided endocardial defibrillation lead (BEDL). The results demonstrated that comparable PDI values and PDI changes with epinephrine induced sinus tachycardia were obtained with all three tested sensing configurations: conventional unipolar, tip electrode to right ventricular defibrillation electrode, and tip electrode to superior vena cava defibrillation electrode. Therefore, the BEDL can be used to measure PDI data, which possibly may improve tachyarrhythmia classification in an ICD, without compromising its defibrillation protection.", "contents": "The measurement of the paced depolarization integral using the braided endocardial lead. Previous studies have shown that the paced depolarization integral (PDI) data recorded in unipolar configuration could potentially improve the specificity of tachyarrhythmia classification in an implantable cardioverter defibrillator (ICD). However, the defibrillation protection would be compromised if the ICD case were used as an indifferent electrode. Since transvenous defibrillation leads are being investigated to be used with ICDs, this study determined if reliable PDI data could be obtained using the braided endocardial defibrillation lead (BEDL). The results demonstrated that comparable PDI values and PDI changes with epinephrine induced sinus tachycardia were obtained with all three tested sensing configurations: conventional unipolar, tip electrode to right ventricular defibrillation electrode, and tip electrode to superior vena cava defibrillation electrode. Therefore, the BEDL can be used to measure PDI data, which possibly may improve tachyarrhythmia classification in an ICD, without compromising its defibrillation protection."} {"id": "PMID:1279588", "title": "Analysis of set screw and side-lock connector reliability.", "content": "A retrospective review of complications with connectors and lead-to-header interfaces was performed following 649 pacing procedures between 1980 and 1990. There were 88 lead revisions (13.6%), 81 device replacements or modifications (12.5%), and 480 new implants (74%) using devices of five manufacturers. Two basic connector types were studied, one utilizing a set screw and the other using a side-lock compression fitting. The set screw makes electrical contact and mechanically secures the lead connector pin with a set screw insulated by a self-sealing grommet or an integral or separate set screw cover. The side-lock makes electrical contact with an automatic spring mechanism while the plastic lead terminal is secured in the connector block of the pacemaker by a Delrin side-lock compression fitting. Four hundred fifty-nine set screw connector devices were followed for up to 12 years with 14 complications (3.1%) whereas 82 side-lock connector devices were followed for up to 5 years with one complication (1.2%). The set screw and side-lock connectors were reliable over the period of follow-up. Although the complication rate appeared lower with the side-lock, follow-up was shorter and the number of implants smaller. With the leads used in this study, the side-lock proved to be a desirable feature due to simplicity, speed, safety, and ease of use. One limitation is the requirement for a precise IS-1 connector terminal diameter.", "contents": "Analysis of set screw and side-lock connector reliability. A retrospective review of complications with connectors and lead-to-header interfaces was performed following 649 pacing procedures between 1980 and 1990. There were 88 lead revisions (13.6%), 81 device replacements or modifications (12.5%), and 480 new implants (74%) using devices of five manufacturers. Two basic connector types were studied, one utilizing a set screw and the other using a side-lock compression fitting. The set screw makes electrical contact and mechanically secures the lead connector pin with a set screw insulated by a self-sealing grommet or an integral or separate set screw cover. The side-lock makes electrical contact with an automatic spring mechanism while the plastic lead terminal is secured in the connector block of the pacemaker by a Delrin side-lock compression fitting. Four hundred fifty-nine set screw connector devices were followed for up to 12 years with 14 complications (3.1%) whereas 82 side-lock connector devices were followed for up to 5 years with one complication (1.2%). The set screw and side-lock connectors were reliable over the period of follow-up. Although the complication rate appeared lower with the side-lock, follow-up was shorter and the number of implants smaller. With the leads used in this study, the side-lock proved to be a desirable feature due to simplicity, speed, safety, and ease of use. One limitation is the requirement for a precise IS-1 connector terminal diameter."} {"id": "PMID:1279589", "title": "In vitro evaluation of new design lead anchoring sleeves.", "content": "The purpose of this study was to evaluate various new lead anchoring sleeve designs. These designs were intended to allow coaxial bipolar leads to be tied down and remain securely in position with minimal damage to the lead body, whether tied down with moderate or high tie forces. Axial grooves were made on the outer and/or inner walls of various anchoring sleeve designs. Anchoring sleeves made of extra tear resistant (ETR) platinum catalyzed and peroxide catalyzed (MDX) silicone rubber of various shore, hardness were tested on various Siemens Pacesetter (S-P) and other manufacturers' lead bodies. Tests to slide the sleeves were conducted with the leads in dry and wet conditions, and with and without the Fast-Pass (Siemens Pacesetter, Inc.) coating for lubriciousness. Tie-down deformation of coils was measured from x-ray photos. Mechanical tests and stress calculations were also done to evaluate the mechanical properties of the different lead bodies being tested. The test results showed that compared with existing sleeves, the new design MDX sleeves with axial grooves on the outer wall of the anchoring sleeves provided much lower resultant deformation (62%-84%) on leads when tied down tightly, and exhibited similar sliding forces. Also, it was determined that the MDX anchoring sleeves provided much improved slip forces of two to three times higher than the ETR sleeves. Tie-down damage can also be significantly reduced by strengthening lead bodies. With the protection of the new sleeves, the tie-down damage of S-P leads was the lowest among all the manufacturers' polyurethane or silicone leads tested.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "In vitro evaluation of new design lead anchoring sleeves. The purpose of this study was to evaluate various new lead anchoring sleeve designs. These designs were intended to allow coaxial bipolar leads to be tied down and remain securely in position with minimal damage to the lead body, whether tied down with moderate or high tie forces. Axial grooves were made on the outer and/or inner walls of various anchoring sleeve designs. Anchoring sleeves made of extra tear resistant (ETR) platinum catalyzed and peroxide catalyzed (MDX) silicone rubber of various shore, hardness were tested on various Siemens Pacesetter (S-P) and other manufacturers' lead bodies. Tests to slide the sleeves were conducted with the leads in dry and wet conditions, and with and without the Fast-Pass (Siemens Pacesetter, Inc.) coating for lubriciousness. Tie-down deformation of coils was measured from x-ray photos. Mechanical tests and stress calculations were also done to evaluate the mechanical properties of the different lead bodies being tested. The test results showed that compared with existing sleeves, the new design MDX sleeves with axial grooves on the outer wall of the anchoring sleeves provided much lower resultant deformation (62%-84%) on leads when tied down tightly, and exhibited similar sliding forces. Also, it was determined that the MDX anchoring sleeves provided much improved slip forces of two to three times higher than the ETR sleeves. Tie-down damage can also be significantly reduced by strengthening lead bodies. With the protection of the new sleeves, the tie-down damage of S-P leads was the lowest among all the manufacturers' polyurethane or silicone leads tested.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279590", "title": "Septal His-Purkinje ventricular pacing in canines: a new endocardial electrode approach.", "content": "Ventricular activation sequences and cardiac performance are influenced by pacing sites. Stimulation of or close to the specialized atrioventricular (AV) conduction system optimizes paced ventricular function compared to alternative epi- or endocardial muscle conduction sites. This study reports a new endocardial electrode implant approach to approximate septal His-Purkinje ventricular pacing. Five 6-month-old beagles were used. A custom, platinum-iridium, exposed helical screw electrode (Medtronic, Inc.), 4.5-mm long, with a 17.8-mm2 surface area, was designed with a polyurethane covered 4 filar MP35N nickle conductor lead. An 8 French sheath (USCI, Inc.) was modified as introducer to permit simultaneous implant intracardiac pressure and electrogram recordings. Following a thoracotomy, the introducer was inserted through the right atrial appendage and advanced to record optimal His-bundle electrogram while maintaining atrial pressure along the septal tricuspid valve annulus. After electrode implant, ECG demonstrated narrow paced QRS morphology. Mean implant values showed sensed R wave 6.3 mV, slew rate 0.65 V/sec, pacing impedance 319 ohms, and threshold 0.9 V/3.3 mA at 0.5-msec output. Necropsy showed implant above the tricuspid annulus with electrode extension into and contained within the proximal ventricular septum. This study demonstrates that an endocardial septal approach to His-Purkinje ventricular pacing to optimize paced ventricular function is feasible with a new electrode design and precise septal implant technique. Alternative introducer designs may permit transvenous application of this approach.", "contents": "Septal His-Purkinje ventricular pacing in canines: a new endocardial electrode approach. Ventricular activation sequences and cardiac performance are influenced by pacing sites. Stimulation of or close to the specialized atrioventricular (AV) conduction system optimizes paced ventricular function compared to alternative epi- or endocardial muscle conduction sites. This study reports a new endocardial electrode implant approach to approximate septal His-Purkinje ventricular pacing. Five 6-month-old beagles were used. A custom, platinum-iridium, exposed helical screw electrode (Medtronic, Inc.), 4.5-mm long, with a 17.8-mm2 surface area, was designed with a polyurethane covered 4 filar MP35N nickle conductor lead. An 8 French sheath (USCI, Inc.) was modified as introducer to permit simultaneous implant intracardiac pressure and electrogram recordings. Following a thoracotomy, the introducer was inserted through the right atrial appendage and advanced to record optimal His-bundle electrogram while maintaining atrial pressure along the septal tricuspid valve annulus. After electrode implant, ECG demonstrated narrow paced QRS morphology. Mean implant values showed sensed R wave 6.3 mV, slew rate 0.65 V/sec, pacing impedance 319 ohms, and threshold 0.9 V/3.3 mA at 0.5-msec output. Necropsy showed implant above the tricuspid annulus with electrode extension into and contained within the proximal ventricular septum. This study demonstrates that an endocardial septal approach to His-Purkinje ventricular pacing to optimize paced ventricular function is feasible with a new electrode design and precise septal implant technique. Alternative introducer designs may permit transvenous application of this approach."} {"id": "PMID:1279591", "title": "Testing of work environments for electromagnetic interference.", "content": "A challenge for pacemaker therapists is whether a patient working in an environment with the potential for electromagnetic interference (EMI) can return to their work after a pacemaker has been implanted. Common practice has been to prohibit pacemaker patients from using electric welding machines. Twelve work environments and a new method for monitoring the pacemaker rhythm in the presence of EMI were tested. The new method uses a special memory called the event record found in several Siemens Pacesetter pacemaker models. Surface ECGs with a marking system, intracardiac electrograms, and a digital monitor were used to verify the results with event records. The results from several sources of EMI are reported. Twenty-one in vivo and in vitro tests were performed in the work environments of 12 patients. Event records were useful and accurate both in vivo and in vitro. Electric are welding machines up to 225 A did not affect these pacemakers. Arc welding machines using 1,000 A or more inhibited the in vitro test system within 1 or 2 meters of the weld or power generator. Electric welding machines with high frequency voltage superimposed on the welding current affected the pacemaker when it was within 2 meters of the power unit and 1 meter of the weld. Very large industrial degaussing coils affected pacemakers within 2 meters. The test method using event records was found to be an effective addition to monitoring the pacemaker. These results are specific for the pacemaker models tested. Such testing allows the physician to make a knowledgeable decision regarding return to work for the pacemaker patient in a high EMI environment.", "contents": "Testing of work environments for electromagnetic interference. A challenge for pacemaker therapists is whether a patient working in an environment with the potential for electromagnetic interference (EMI) can return to their work after a pacemaker has been implanted. Common practice has been to prohibit pacemaker patients from using electric welding machines. Twelve work environments and a new method for monitoring the pacemaker rhythm in the presence of EMI were tested. The new method uses a special memory called the event record found in several Siemens Pacesetter pacemaker models. Surface ECGs with a marking system, intracardiac electrograms, and a digital monitor were used to verify the results with event records. The results from several sources of EMI are reported. Twenty-one in vivo and in vitro tests were performed in the work environments of 12 patients. Event records were useful and accurate both in vivo and in vitro. Electric are welding machines up to 225 A did not affect these pacemakers. Arc welding machines using 1,000 A or more inhibited the in vitro test system within 1 or 2 meters of the weld or power generator. Electric welding machines with high frequency voltage superimposed on the welding current affected the pacemaker when it was within 2 meters of the power unit and 1 meter of the weld. Very large industrial degaussing coils affected pacemakers within 2 meters. The test method using event records was found to be an effective addition to monitoring the pacemaker. These results are specific for the pacemaker models tested. Such testing allows the physician to make a knowledgeable decision regarding return to work for the pacemaker patient in a high EMI environment."} {"id": "PMID:1279592", "title": "The clinical relevance of electromyopotential oversensing in current unipolar devices.", "content": "Electromyopotential oversensing of unipolar pacemakers was first appreciated 20 years ago, but its prevalence in present day devices is less well defined. Thirty-four pacemaker patients, only two with symptoms suggestive of oversensing, were evaluated in unipolar settings to assess the frequency of provocation of oversensing in one or, if present, both pacing channels. The sensing threshold of each patient, whenever possible, was recorded as well. Atrial oversensing occurred in 11/18 patients (61%), all at sensitivities in the 0.4-1.0 mV range. Ventricular oversensing was noted in 13/33 patients (39%), with all but one programmed to settings of 1.25 mV or more sensitive (i.e. < 1.25 mV). Twenty six of 26 patients amenable to testing had ventricular sensing thresholds of at least 4.0 mV or more. Of the 15 patients amenable to atrial sensing threshold testing, 4 had a threshold of 1.0 mV or < 1.0 mV, 6 had thresholds between 1.0-2.0 mV, and 5 sensed at settings > 2.0 mV. Electromyopotential oversensing remains a relevant issue in current day unipolar pacemakers. Most patients do not describe symptoms related to electromyopotential interference, yet such interference is frequently provoked. Oversensing is common at high sensitivities typically utilized for atrial sensing, but quite unusual at settings necessary for adequate ventricular sensing. Programming unipolar devices to unnecessarily high sensitivities should be avoided or serious consequences may result.", "contents": "The clinical relevance of electromyopotential oversensing in current unipolar devices. Electromyopotential oversensing of unipolar pacemakers was first appreciated 20 years ago, but its prevalence in present day devices is less well defined. Thirty-four pacemaker patients, only two with symptoms suggestive of oversensing, were evaluated in unipolar settings to assess the frequency of provocation of oversensing in one or, if present, both pacing channels. The sensing threshold of each patient, whenever possible, was recorded as well. Atrial oversensing occurred in 11/18 patients (61%), all at sensitivities in the 0.4-1.0 mV range. Ventricular oversensing was noted in 13/33 patients (39%), with all but one programmed to settings of 1.25 mV or more sensitive (i.e. < 1.25 mV). Twenty six of 26 patients amenable to testing had ventricular sensing thresholds of at least 4.0 mV or more. Of the 15 patients amenable to atrial sensing threshold testing, 4 had a threshold of 1.0 mV or < 1.0 mV, 6 had thresholds between 1.0-2.0 mV, and 5 sensed at settings > 2.0 mV. Electromyopotential oversensing remains a relevant issue in current day unipolar pacemakers. Most patients do not describe symptoms related to electromyopotential interference, yet such interference is frequently provoked. Oversensing is common at high sensitivities typically utilized for atrial sensing, but quite unusual at settings necessary for adequate ventricular sensing. Programming unipolar devices to unnecessarily high sensitivities should be avoided or serious consequences may result."} {"id": "PMID:1279593", "title": "Interaction between permanent cardiac pacing and electrocautery: the significance of electrode position.", "content": "The danger in utilizing electrocautery during a surgical procedure on a pacemaker patient depends, to a great extent, on the position of the electrodes. We have studied this influence in an experimental model consisting of a plexiglass tank filled with a saline solution. Seven pacemakers were successively attached to an immersed and fixed frame and connected to a lead whose tip remains in the same location throughout the experiments. An ERBOTOM T 400 C generator (450 kHz) was used in an unmodulated unipolar mode at a maximum output (400 W). The high frequency current was delivered between a patch located successively at six preset positions in the tank and another electrode applied to 176 surface locations. For each position, we measured the currents in the lead with a separate measurement circuit connected in parallel on the same lead. Results were displayed on a map. Regardless of the patch position, currents were: (1) at a maximum when high frequency was delivered close to the pacemakers and around the tip of the lead; (2) negligible when applied to the path followed by the lead; and (3) a function of the distance between electrodes. These results may help to formulate recommendations to prevent accidents when using electrocautery in pacemaker patients.", "contents": "Interaction between permanent cardiac pacing and electrocautery: the significance of electrode position. The danger in utilizing electrocautery during a surgical procedure on a pacemaker patient depends, to a great extent, on the position of the electrodes. We have studied this influence in an experimental model consisting of a plexiglass tank filled with a saline solution. Seven pacemakers were successively attached to an immersed and fixed frame and connected to a lead whose tip remains in the same location throughout the experiments. An ERBOTOM T 400 C generator (450 kHz) was used in an unmodulated unipolar mode at a maximum output (400 W). The high frequency current was delivered between a patch located successively at six preset positions in the tank and another electrode applied to 176 surface locations. For each position, we measured the currents in the lead with a separate measurement circuit connected in parallel on the same lead. Results were displayed on a map. Regardless of the patch position, currents were: (1) at a maximum when high frequency was delivered close to the pacemakers and around the tip of the lead; (2) negligible when applied to the path followed by the lead; and (3) a function of the distance between electrodes. These results may help to formulate recommendations to prevent accidents when using electrocautery in pacemaker patients."} {"id": "PMID:1279594", "title": "The lithium/iodine battery: a historical perspective.", "content": "The lithium/iodine-polyvinylpyridine battery, first implanted 20 years ago, has become the power source of choice for the cardiac pacemaker. Over the last 20 years, improvements in cell chemistry, cell design, and modeling of cell performance have been made. Cells today exhibit an energy density over three times as great as cells produced in 1972. Well over 2 million pacemakers have been implanted with this chemistry, and the system has exhibited excellent reliability.", "contents": "The lithium/iodine battery: a historical perspective. The lithium/iodine-polyvinylpyridine battery, first implanted 20 years ago, has become the power source of choice for the cardiac pacemaker. Over the last 20 years, improvements in cell chemistry, cell design, and modeling of cell performance have been made. Cells today exhibit an energy density over three times as great as cells produced in 1972. Well over 2 million pacemakers have been implanted with this chemistry, and the system has exhibited excellent reliability."} {"id": "PMID:1279595", "title": "Pacemaker dependency after coronary artery bypass.", "content": "A retrospective study was carried out on 36 patients (33 males and 3 females) to determine the incidence of VVI pacemaker dependency following coronary artery bypass surgery. Pacemaker dependency was defined as the presence of pacemaker activity when pacing rate was programmed at 50 beats/min and/or when no hemodynamic adequate rhythm was present during pulse generator replacement. The patients were divided into two groups: (group I) 26 patients with complete atrioventricular (AV) block developing in the early postoperative period. In most of them a pacemaker was implanted up to 3 weeks following surgery (range 2 days to 1 year); (group II) ten patients in whom the indication for pacemaker implantation was sick sinus syndrome with sinus arrest and/or tachy-bradycardia. These patients underwent pacemaker implantation at varying periods of time following surgery (range 12 days to 4 years). Unipolar endocardial leads with VVI programmable pacemakers were implanted in all patients included in this study. Mean follow-up time was 3 years. In group I the pacemaker dependency rate was 65%, whereas in group II it was 30% throughout the follow-up period. It is concluded that the low incidence of pacemaker dependency in patients who undergo pacemaker implantation after coronary bypass surgery necessitates frequent evaluation in the nondependent patient, in order to reassess the need for the pacemaker before pulse generator replacement. Such reassessment should probably include prolonged ambulatory monitoring as well as invasive evaluation of the conduction system, if avoidance of pulse generator replacement is considered.", "contents": "Pacemaker dependency after coronary artery bypass. A retrospective study was carried out on 36 patients (33 males and 3 females) to determine the incidence of VVI pacemaker dependency following coronary artery bypass surgery. Pacemaker dependency was defined as the presence of pacemaker activity when pacing rate was programmed at 50 beats/min and/or when no hemodynamic adequate rhythm was present during pulse generator replacement. The patients were divided into two groups: (group I) 26 patients with complete atrioventricular (AV) block developing in the early postoperative period. In most of them a pacemaker was implanted up to 3 weeks following surgery (range 2 days to 1 year); (group II) ten patients in whom the indication for pacemaker implantation was sick sinus syndrome with sinus arrest and/or tachy-bradycardia. These patients underwent pacemaker implantation at varying periods of time following surgery (range 12 days to 4 years). Unipolar endocardial leads with VVI programmable pacemakers were implanted in all patients included in this study. Mean follow-up time was 3 years. In group I the pacemaker dependency rate was 65%, whereas in group II it was 30% throughout the follow-up period. It is concluded that the low incidence of pacemaker dependency in patients who undergo pacemaker implantation after coronary bypass surgery necessitates frequent evaluation in the nondependent patient, in order to reassess the need for the pacemaker before pulse generator replacement. Such reassessment should probably include prolonged ambulatory monitoring as well as invasive evaluation of the conduction system, if avoidance of pulse generator replacement is considered."} {"id": "PMID:1279596", "title": "Can the heart be chronically paced with electrodes on the pericardial surface?", "content": "During implantable defibrillator (ICD) operations, we measured acute and chronic transpericardial bipolar pacing thresholds through standard myocardial surface electrodes sewn on the pericardium for chronic ICD QRS rate-sensing use. We compared observations in 24 patients on day 0 with chronic measurements in seven patients at 27.4 +/- 12.1 (median 31.7) months. The leads were used only for QRS rate-sensing, not for pacing, during the time between acute and chronic measurements. Acute transpericardial pacing threshold at 0.5-msec stimulus duration on day 0 was 4.5 +/- 2.19 V (standard deviation), median 3.5 V, and at median time 964 days postimplantation was 3.8 +/- 2.07 V, median 3.5 V. Mean acute pacing current threshold was 3.7 +/- 1.90 mA, n = 23, and chronic was 2.7 +/- 1.79 mA, n = 6. Acute bipolar impedance was 1,209 +/- 383 ohms, median 1,138 ohms, and chronic was 1,550 +/- 358 ohms, median 1,410 ohms, n = 7. Acute bipolar QRS amplitude was 12.3 +/- 5.93 mV, median 12.1 mV, n = 24, and chronic was 13.5 +/- 8.5 mV, median 17.2 mV, n = 7. None of the changes between the acute and chronic states was statistically significant, with the exception of bipolar impedance (P = 0.054). We concluded that: (1) transpericardial pacing threshold did not increase with time; (2) initial and chronic pacing impedances were high and current low; (3) QRS amplitudes were highly satisfactory for defibrillator rate-sensing; and (4) this approach to ICD implantation left the surgically virgin heart unscarred to make future transplantation easier, and enhanced safety when previous cardiac operations had been done.", "contents": "Can the heart be chronically paced with electrodes on the pericardial surface? During implantable defibrillator (ICD) operations, we measured acute and chronic transpericardial bipolar pacing thresholds through standard myocardial surface electrodes sewn on the pericardium for chronic ICD QRS rate-sensing use. We compared observations in 24 patients on day 0 with chronic measurements in seven patients at 27.4 +/- 12.1 (median 31.7) months. The leads were used only for QRS rate-sensing, not for pacing, during the time between acute and chronic measurements. Acute transpericardial pacing threshold at 0.5-msec stimulus duration on day 0 was 4.5 +/- 2.19 V (standard deviation), median 3.5 V, and at median time 964 days postimplantation was 3.8 +/- 2.07 V, median 3.5 V. Mean acute pacing current threshold was 3.7 +/- 1.90 mA, n = 23, and chronic was 2.7 +/- 1.79 mA, n = 6. Acute bipolar impedance was 1,209 +/- 383 ohms, median 1,138 ohms, and chronic was 1,550 +/- 358 ohms, median 1,410 ohms, n = 7. Acute bipolar QRS amplitude was 12.3 +/- 5.93 mV, median 12.1 mV, n = 24, and chronic was 13.5 +/- 8.5 mV, median 17.2 mV, n = 7. None of the changes between the acute and chronic states was statistically significant, with the exception of bipolar impedance (P = 0.054). We concluded that: (1) transpericardial pacing threshold did not increase with time; (2) initial and chronic pacing impedances were high and current low; (3) QRS amplitudes were highly satisfactory for defibrillator rate-sensing; and (4) this approach to ICD implantation left the surgically virgin heart unscarred to make future transplantation easier, and enhanced safety when previous cardiac operations had been done."} {"id": "PMID:1279597", "title": "Cardiac pacing in neonates, infants, and preschool children.", "content": "A series of 37 children < 5 years old at pacemaker implant were followed from 1 to 105 months. Five of 37 patients required reoperation for battery depletion while two required reoperation for exit block of epicardial ventricular leads. Each patient paced in the DDD or AAI mode was still in the original mode at the end of follow up.", "contents": "Cardiac pacing in neonates, infants, and preschool children. A series of 37 children < 5 years old at pacemaker implant were followed from 1 to 105 months. Five of 37 patients required reoperation for battery depletion while two required reoperation for exit block of epicardial ventricular leads. Each patient paced in the DDD or AAI mode was still in the original mode at the end of follow up."} {"id": "PMID:1279598", "title": "Incidence and predictors of loss of pacing in the atrium in patients with sick sinus syndrome.", "content": "Atrial and dual-chamber pacemakers may be associated with reduced morbidity in patients with the sick sinus syndrome (SSS). In some patients, however, subsequent development of chronic atrial fibrillation or atrial lead failure make long-term pacing in the atrium not feasible. We analyzed the incidence and predictors of loss of atrial pacing in 395 consecutive patients with SSS (376 with dual-chamber pacemakers and 19 with single-chamber atrial pacemakers). None of them was in established atrial fibrillation at time of implant. Patients were followed-up for 55 +/- 35 months. Actuarial survival of effective atrial pacing was 92.5% at 1 year, 85% at 5 years, and 76.5% at 10 years. Overall, 60 patients lost atrial pacing. The most frequent cause was the development of chronic atrial fibrillation (53 patients). By multivariate analysis (Cox proportional-hazards model), independent predictors of loss of pacing in the atrium were preimplant episodes of paroxysmal atrial fibrillation (PAF) lasting more than 1 hour (P < 0.001; hazard ratio (HR) = 4.3); prior history of PAF for more than 5 years (P < 0.001; HR = 2.67; and endocardial P wave < 2 mV (P = 0.014; HR = 1.96). In a subgroup of patients (n = 187) who had echocardiograms, a left atrium > 50 mm was also an independent predictor of loss of atrial pacing (P = 0.028; HR = 2.28).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Incidence and predictors of loss of pacing in the atrium in patients with sick sinus syndrome. Atrial and dual-chamber pacemakers may be associated with reduced morbidity in patients with the sick sinus syndrome (SSS). In some patients, however, subsequent development of chronic atrial fibrillation or atrial lead failure make long-term pacing in the atrium not feasible. We analyzed the incidence and predictors of loss of atrial pacing in 395 consecutive patients with SSS (376 with dual-chamber pacemakers and 19 with single-chamber atrial pacemakers). None of them was in established atrial fibrillation at time of implant. Patients were followed-up for 55 +/- 35 months. Actuarial survival of effective atrial pacing was 92.5% at 1 year, 85% at 5 years, and 76.5% at 10 years. Overall, 60 patients lost atrial pacing. The most frequent cause was the development of chronic atrial fibrillation (53 patients). By multivariate analysis (Cox proportional-hazards model), independent predictors of loss of pacing in the atrium were preimplant episodes of paroxysmal atrial fibrillation (PAF) lasting more than 1 hour (P < 0.001; hazard ratio (HR) = 4.3); prior history of PAF for more than 5 years (P < 0.001; HR = 2.67; and endocardial P wave < 2 mV (P = 0.014; HR = 1.96). In a subgroup of patients (n = 187) who had echocardiograms, a left atrium > 50 mm was also an independent predictor of loss of atrial pacing (P = 0.028; HR = 2.28).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279599", "title": "Incidence and predictors of syncope in paced patients with sick sinus syndrome.", "content": "In spite of a normal pacemaker function, syncope still occurs in some patients with sick sinus syndrome (SSS). Causes often remain unknown. To identify predictors and etiologies of this bothersome symptom, we studied 507 patients who received atrial, ventricular, and dual-chamber pacemakers for SSS. During a mean follow-up of 62 +/- 38 months, actuarial incidence of syncope was 3% at 1 year, 8% at 5 years, and 13% at 10 years. Causes were vasovagal (18%), orthostatic hypotension (25.5%), rapid atrial tachyarrhythmias (11.5%), ventricular tachycardia (5%), acute myocardial ischemia (2.5%), and pacemaker/lead malfunction (6.5%). In 13 patients (29.5%), syncope remained unexplained. The only preimplant predictor for syncope was syncope as primary indication for pacemaker implant. Electrocardiographic correlation with bradycardia was not a predictor of relief of syncope during the follow-up. (1) syncope in paced patients with SSS has multiple etiologies and may be multifactorial; (2) the only predictor of syncope after pacemaker implant is the occurrence of preimplant syncope as the main indication for pacing; (3) extensive Holter monitoring is not useful to document bradycardiac origin of syncope nor to predict its recurrence; (4) SSS probably overlaps with other entities such as autonomic dysfunction, vasovagal syncope, carotid sinus hypersensitivity, and venous pooling, which would provide an explanation for recurrent syncope in patients with normal pacemaker function.", "contents": "Incidence and predictors of syncope in paced patients with sick sinus syndrome. In spite of a normal pacemaker function, syncope still occurs in some patients with sick sinus syndrome (SSS). Causes often remain unknown. To identify predictors and etiologies of this bothersome symptom, we studied 507 patients who received atrial, ventricular, and dual-chamber pacemakers for SSS. During a mean follow-up of 62 +/- 38 months, actuarial incidence of syncope was 3% at 1 year, 8% at 5 years, and 13% at 10 years. Causes were vasovagal (18%), orthostatic hypotension (25.5%), rapid atrial tachyarrhythmias (11.5%), ventricular tachycardia (5%), acute myocardial ischemia (2.5%), and pacemaker/lead malfunction (6.5%). In 13 patients (29.5%), syncope remained unexplained. The only preimplant predictor for syncope was syncope as primary indication for pacemaker implant. Electrocardiographic correlation with bradycardia was not a predictor of relief of syncope during the follow-up. (1) syncope in paced patients with SSS has multiple etiologies and may be multifactorial; (2) the only predictor of syncope after pacemaker implant is the occurrence of preimplant syncope as the main indication for pacing; (3) extensive Holter monitoring is not useful to document bradycardiac origin of syncope nor to predict its recurrence; (4) SSS probably overlaps with other entities such as autonomic dysfunction, vasovagal syncope, carotid sinus hypersensitivity, and venous pooling, which would provide an explanation for recurrent syncope in patients with normal pacemaker function."} {"id": "PMID:1279600", "title": "Long-term intrinsic pacemaker function in patients paced for sinus node deficiency after cardiac transplantation.", "content": "Fifteen cardiac transplant recipients requiring permanent pacing (AAI, n = 9; VVI, n = 6; rate responsive devices, n = 11) for postoperative sinus node (SN) insufficiency underwent evaluation of long-term SN function 240 to 1,461 days after transplantation. The intrinsic rhythm at the time of discharge was sinus in 7 patients; junctional escape in 6 patients; and pacemaker dependent in 2 patients. At follow-up, 5 patients had regained regular sinus rhythm, accounting for a total of 11 patients in sinus rhythm while 4 patients were in junctional bradycardia. The SN recovery time as determined by the permanent pacemaker was normal (< 1,500 msec) in only 1/8 patients in whom it was determined, although 4 of these 8 patients were temporarily overriding the pacemaker during ambulatory monitoring. Patients with pathological SN recovery times included 3 patients with late return of sinus rhythm and 4 patients who had recovered normal sinus rhythm before their discharge from the hospital. Three patients developed late symptoms despite apparent early normalization and underwent delayed pacemaker implantations on postoperative days 35, 52, and 225, respectively. We conclude that, in patients requiring pacemaker implantation after cardiac transplantation, normalization of SN function cannot be inferred from just return of sinus rhythm, regardless of whether it occurs early or late. These findings may have implications when a pacemaker exchange or explantation is being considered.", "contents": "Long-term intrinsic pacemaker function in patients paced for sinus node deficiency after cardiac transplantation. Fifteen cardiac transplant recipients requiring permanent pacing (AAI, n = 9; VVI, n = 6; rate responsive devices, n = 11) for postoperative sinus node (SN) insufficiency underwent evaluation of long-term SN function 240 to 1,461 days after transplantation. The intrinsic rhythm at the time of discharge was sinus in 7 patients; junctional escape in 6 patients; and pacemaker dependent in 2 patients. At follow-up, 5 patients had regained regular sinus rhythm, accounting for a total of 11 patients in sinus rhythm while 4 patients were in junctional bradycardia. The SN recovery time as determined by the permanent pacemaker was normal (< 1,500 msec) in only 1/8 patients in whom it was determined, although 4 of these 8 patients were temporarily overriding the pacemaker during ambulatory monitoring. Patients with pathological SN recovery times included 3 patients with late return of sinus rhythm and 4 patients who had recovered normal sinus rhythm before their discharge from the hospital. Three patients developed late symptoms despite apparent early normalization and underwent delayed pacemaker implantations on postoperative days 35, 52, and 225, respectively. We conclude that, in patients requiring pacemaker implantation after cardiac transplantation, normalization of SN function cannot be inferred from just return of sinus rhythm, regardless of whether it occurs early or late. These findings may have implications when a pacemaker exchange or explantation is being considered."} {"id": "PMID:1279601", "title": "Intravenous adenosine: a noninvasive diagnostic test for sick sinus syndrome.", "content": "Adenosine has a well established negative chronotropic effect on the sinoatrial node. The most widely utilized test of sinus node function remains the sinus node recovery time (SNRT), which generally requires catheterization. We compared the effect of adenosine (150 mcg/kg IV) on the lengthening of sinus cycle length (ADO:SCL) in 12 control patients (group I) and in 11 patients with clinical sick sinus syndrome (SSS) (group II), eight of whom had undergone prior permanent pacemaker implantation. Using 675 msec as an abnormal result indicating sinus node dysfunction (two standard deviations above the mean value established in controls), ADO:SCL had a sensitivity and specificity of 64% and 100%, which were equal to that observed for the corrected sinus node recovery time (CSNRT) (abnormal value > or = 550 msec). There was a significant difference in the CSNRT between group I (304 +/- 149 msec) and group II (1,199 +/- 916 msec, P = 0.003). There was no significant difference in ADO:SCL between groups I (256 +/- 210 msec) and group II (1,213 +/- 1,719 msec, P = 0.069); however, there was substantial overlap between patients exhibiting an abnormal ADO:SCL and CSNRT. As such, a significant difference in ADO:SCL was evident between group II patients (1,784 +/- 1,950 msec, n = 7) exhibiting an abnormal CSNRT and group I patients, P = 0.014. In conclusion, ADO:SCL has the same sensitivity and specificity for sinus node dysfunction as compared to the CSNRT. Intravenous adenosine may prove to be a useful noninvasive test to assess the need for permanent pacemaker implantation.", "contents": "Intravenous adenosine: a noninvasive diagnostic test for sick sinus syndrome. Adenosine has a well established negative chronotropic effect on the sinoatrial node. The most widely utilized test of sinus node function remains the sinus node recovery time (SNRT), which generally requires catheterization. We compared the effect of adenosine (150 mcg/kg IV) on the lengthening of sinus cycle length (ADO:SCL) in 12 control patients (group I) and in 11 patients with clinical sick sinus syndrome (SSS) (group II), eight of whom had undergone prior permanent pacemaker implantation. Using 675 msec as an abnormal result indicating sinus node dysfunction (two standard deviations above the mean value established in controls), ADO:SCL had a sensitivity and specificity of 64% and 100%, which were equal to that observed for the corrected sinus node recovery time (CSNRT) (abnormal value > or = 550 msec). There was a significant difference in the CSNRT between group I (304 +/- 149 msec) and group II (1,199 +/- 916 msec, P = 0.003). There was no significant difference in ADO:SCL between groups I (256 +/- 210 msec) and group II (1,213 +/- 1,719 msec, P = 0.069); however, there was substantial overlap between patients exhibiting an abnormal ADO:SCL and CSNRT. As such, a significant difference in ADO:SCL was evident between group II patients (1,784 +/- 1,950 msec, n = 7) exhibiting an abnormal CSNRT and group I patients, P = 0.014. In conclusion, ADO:SCL has the same sensitivity and specificity for sinus node dysfunction as compared to the CSNRT. Intravenous adenosine may prove to be a useful noninvasive test to assess the need for permanent pacemaker implantation."} {"id": "PMID:1279602", "title": "Atrioventricular conduction disturbances in patients with sinoatrial node disease and atrial pacing.", "content": "In sinoatrial node disease (SND) atrial pacing may be limited by progression of AV block. The incidence of AV block after AAI systems implantation range, according to various authors, from 0% to 12%. The aim of this study was to examine the AV conduction disturbances that forced a change in the mode of pacing in patients with AAI pacemakers. The information was collected retrospectively from a cohort of 122 patients. The follow-up period ranged from 5 to 83 months (mean = 35). Among these patients there were 37 with sinus bradycardia and 85 with bradycardia-tachycardia syndrome. Their mean age was 63 years. Before AAI pacemaker insertion, all patients had normal AV conduction on 12-lead ECG, and all but five had a Wenckebach cycle length shorter than 500 msec. Seven out of these 122 patients (5.7%) developed symptomatic conduction disturbances (second-degree type I AV block in five, second degree type II AV block in one, and third-degree AV block in one), necessitating a change from AAI to another mode of pacing. We conclude that progression of AV block after atrial pacemaker implantation in patients with SND is infrequent and mild in the majority of cases. Intraventricular disturbances such as left anterior hemiblock represent contraindication to AAI pacing particularly in patients who may be in need of antiarrhythmic drugs.", "contents": "Atrioventricular conduction disturbances in patients with sinoatrial node disease and atrial pacing. In sinoatrial node disease (SND) atrial pacing may be limited by progression of AV block. The incidence of AV block after AAI systems implantation range, according to various authors, from 0% to 12%. The aim of this study was to examine the AV conduction disturbances that forced a change in the mode of pacing in patients with AAI pacemakers. The information was collected retrospectively from a cohort of 122 patients. The follow-up period ranged from 5 to 83 months (mean = 35). Among these patients there were 37 with sinus bradycardia and 85 with bradycardia-tachycardia syndrome. Their mean age was 63 years. Before AAI pacemaker insertion, all patients had normal AV conduction on 12-lead ECG, and all but five had a Wenckebach cycle length shorter than 500 msec. Seven out of these 122 patients (5.7%) developed symptomatic conduction disturbances (second-degree type I AV block in five, second degree type II AV block in one, and third-degree AV block in one), necessitating a change from AAI to another mode of pacing. We conclude that progression of AV block after atrial pacemaker implantation in patients with SND is infrequent and mild in the majority of cases. Intraventricular disturbances such as left anterior hemiblock represent contraindication to AAI pacing particularly in patients who may be in need of antiarrhythmic drugs."} {"id": "PMID:1279603", "title": "Predictive value of the P wave at implantation for atrial fibrillation after VVI pacemaker implantation.", "content": "This study assesses the value of P wave measurements on the surface ECG at implantation, in the prediction of atrial fibrillation in VVI paced patients. From a consecutive series of 320 pacemaker implantations 172 VVI paced patients for symptomatic atrioventricular block (AVB) (n = 126; mean age 69 +/- 14) or sick sinus syndrome (SSS) (n = 56; mean age 68.6 +/- 12) and in sinus rhythm at implantation were used in this study. P wave duration in V1 is correlated with the incidence of atrial fibrillation during 5 years of follow-up. V1 at implantation was significantly longer (114.6 +/- 2.7 msec) in the patients who developed atrial fibrillation than in those who did not (91.9 +/- 2.7 msec) (P < 0.001). Although positive predictive accuracy increases progressively for higher V1 values for AVB and SSS, the negative predictive and diagnostic accuracy of V1 criteria were less in SSS. Application of the Bayes' theorem showed that in SSS the probability to develop atrial fibrillation is 33% for V1 < 110 msec and is for V1 < 90 msec still higher than that reported in DDD paced patients. In the AVB group the probability to develop atrial fibrillation is 8% for V1 < 110 msec and 6% for V1 < 100 msec. It seems, therefore, that atrial stimulation (AAI or DDD) is always indicated in SSS. In AVB with V1 < 100 msec, DDD pacing, if not needed for other indications, apparently does not offer much benefit in the prophylaxis of atrial fibrillation.", "contents": "Predictive value of the P wave at implantation for atrial fibrillation after VVI pacemaker implantation. This study assesses the value of P wave measurements on the surface ECG at implantation, in the prediction of atrial fibrillation in VVI paced patients. From a consecutive series of 320 pacemaker implantations 172 VVI paced patients for symptomatic atrioventricular block (AVB) (n = 126; mean age 69 +/- 14) or sick sinus syndrome (SSS) (n = 56; mean age 68.6 +/- 12) and in sinus rhythm at implantation were used in this study. P wave duration in V1 is correlated with the incidence of atrial fibrillation during 5 years of follow-up. V1 at implantation was significantly longer (114.6 +/- 2.7 msec) in the patients who developed atrial fibrillation than in those who did not (91.9 +/- 2.7 msec) (P < 0.001). Although positive predictive accuracy increases progressively for higher V1 values for AVB and SSS, the negative predictive and diagnostic accuracy of V1 criteria were less in SSS. Application of the Bayes' theorem showed that in SSS the probability to develop atrial fibrillation is 33% for V1 < 110 msec and is for V1 < 90 msec still higher than that reported in DDD paced patients. In the AVB group the probability to develop atrial fibrillation is 8% for V1 < 110 msec and 6% for V1 < 100 msec. It seems, therefore, that atrial stimulation (AAI or DDD) is always indicated in SSS. In AVB with V1 < 100 msec, DDD pacing, if not needed for other indications, apparently does not offer much benefit in the prophylaxis of atrial fibrillation."} {"id": "PMID:1279604", "title": "Electrophysiological effect of the maze procedure on canine sinoatrial node function.", "content": "The maze procedure is an operation that has had great initial success in curing atrial fibrillation. This procedure includes several right atrial incisions that may interrupt the integrity of the sinoatrial node or its arterial supply. To assess the effect of the maze procedure on sinus node function (SNF), the following studies were performed: sinus node recovery times (SNRT), corrected SNRT (CSNRT), CSNRT under autonomic blockade maximal heart rate and intrinsic heart rates. Thirty-four dogs underwent a right thoracotomy with cardiopulmonary bypass (CPB). The dogs were divided into three groups. Group 1 (n = 9), the sham group, underwent CPB without any incisions. Group 2 (n = 8) underwent CPB and one of the right atrial incisions. Group 3 (n = 18) underwent CPB and all three of the right atrial incisions. SNF was determined before and after the procedure. Groups 1 and 2 had no significant difference in measured SNF acutely after the procedure. In Group 3 the mean SNRT increased from 552 msec to 1,984 msec (P = 0.005). Sinus node dysfunction was corroborated by all studies. In the chronic studies, a trend toward recovery of SNF was observed. The maze procedure results in significant acute sinus node dysfunction. This dysfunction may resolve spontaneously over the ensuing months. Modifications of the maze procedure that avoid the sinus node or its blood supply area may reduce procedure related sinus node dysfunction.", "contents": "Electrophysiological effect of the maze procedure on canine sinoatrial node function. The maze procedure is an operation that has had great initial success in curing atrial fibrillation. This procedure includes several right atrial incisions that may interrupt the integrity of the sinoatrial node or its arterial supply. To assess the effect of the maze procedure on sinus node function (SNF), the following studies were performed: sinus node recovery times (SNRT), corrected SNRT (CSNRT), CSNRT under autonomic blockade maximal heart rate and intrinsic heart rates. Thirty-four dogs underwent a right thoracotomy with cardiopulmonary bypass (CPB). The dogs were divided into three groups. Group 1 (n = 9), the sham group, underwent CPB without any incisions. Group 2 (n = 8) underwent CPB and one of the right atrial incisions. Group 3 (n = 18) underwent CPB and all three of the right atrial incisions. SNF was determined before and after the procedure. Groups 1 and 2 had no significant difference in measured SNF acutely after the procedure. In Group 3 the mean SNRT increased from 552 msec to 1,984 msec (P = 0.005). Sinus node dysfunction was corroborated by all studies. In the chronic studies, a trend toward recovery of SNF was observed. The maze procedure results in significant acute sinus node dysfunction. This dysfunction may resolve spontaneously over the ensuing months. Modifications of the maze procedure that avoid the sinus node or its blood supply area may reduce procedure related sinus node dysfunction."} {"id": "PMID:1279605", "title": "A simple in vivo model to evaluate the effects of antiarrhythmic agents.", "content": "Antiarrhythmic agents alter cardiac conduction, refractoriness, and action potential duration in a rate dependent fashion. A simple in vivo model was developed to measure these variables over a wide range of cycle lengths. Complete heart block was produced in dogs using an 8 French hexapolar ablation catheter, anterior skin electrode, and radiofrequency current (30 W, 13.6 +/- 2.6 seconds). Ventricular pacing and monophasic action potential recordings were performed using a single combination catheter. QRS and action potential durations were measured at multiple cycle lengths and after an abrupt change in paced cycle length. Ventricular effective refractory periods were also measured at multiple cycle lengths. Data obtained during flecainide and d-Sotalol infusions are presented. This simple model allows detailed in vivo evaluation of the electrophysiological effects of antiarrhythmic agents and combinations.", "contents": "A simple in vivo model to evaluate the effects of antiarrhythmic agents. Antiarrhythmic agents alter cardiac conduction, refractoriness, and action potential duration in a rate dependent fashion. A simple in vivo model was developed to measure these variables over a wide range of cycle lengths. Complete heart block was produced in dogs using an 8 French hexapolar ablation catheter, anterior skin electrode, and radiofrequency current (30 W, 13.6 +/- 2.6 seconds). Ventricular pacing and monophasic action potential recordings were performed using a single combination catheter. QRS and action potential durations were measured at multiple cycle lengths and after an abrupt change in paced cycle length. Ventricular effective refractory periods were also measured at multiple cycle lengths. Data obtained during flecainide and d-Sotalol infusions are presented. This simple model allows detailed in vivo evaluation of the electrophysiological effects of antiarrhythmic agents and combinations."} {"id": "PMID:1279606", "title": "Reverse use dependence of antiarrhythmic class Ia, Ib, and Ic: effects of drugs on the action potential duration?", "content": "The prolongation of the action potential duration (APD) induced by sotalol has been shown to be diminished with increasing heart rate. This phenomenon is called \"reverse use dependence.\" We examined the Ia, Ib, and Ic effects of different Class I drugs on the APD under normal and fast stimulation rates (1.0 and 2.5 Hz) in isolated rabbit atrial and ventricular muscles by means of intracellular microelectrodes. Results (n = 98): With 1.0 Hz lidocaine (Ib, 4.3 x 10(-5) M) shortened the APD at 90% repolarization (APD90) in the atrium by 9% and in the ventricle by 8% (NS), whereas quinidine (Ia, 2.2 x 10(-5) M) and prajmaline (Ia, 10(-6) M) prolonged the APD90 in the atrium (quinidine +45%; prajmaline +10%, P < 0.001) and in the ventricle (+42%, P < 0.001; +17%, P < 0.05). Propafenone (Ic, 2.6 x 10(-6) M) showed this effect only in the atrium (APD90 +33%; P < 0.01). With the faster stimulation rate of 2.5 Hz we could not find a significant influence of any drug on the APD90 in the ventricle and only quinidine prolonged the APD90 in the atrium by 16% (P < 0.05). The subclassification of Class I antiarrhythmic drugs that is based on APD modifying influences is only valid under normal heart rates (1.0 Hz). During tachycardia these actions are absent and the phenomenon of \"reverse use dependence\" is found in Class I drugs. Therefore, an additional antiarrhythmic effect due to APD modification by the examined drugs should not be expected at rapid heart rates.", "contents": "Reverse use dependence of antiarrhythmic class Ia, Ib, and Ic: effects of drugs on the action potential duration? The prolongation of the action potential duration (APD) induced by sotalol has been shown to be diminished with increasing heart rate. This phenomenon is called \"reverse use dependence.\" We examined the Ia, Ib, and Ic effects of different Class I drugs on the APD under normal and fast stimulation rates (1.0 and 2.5 Hz) in isolated rabbit atrial and ventricular muscles by means of intracellular microelectrodes. Results (n = 98): With 1.0 Hz lidocaine (Ib, 4.3 x 10(-5) M) shortened the APD at 90% repolarization (APD90) in the atrium by 9% and in the ventricle by 8% (NS), whereas quinidine (Ia, 2.2 x 10(-5) M) and prajmaline (Ia, 10(-6) M) prolonged the APD90 in the atrium (quinidine +45%; prajmaline +10%, P < 0.001) and in the ventricle (+42%, P < 0.001; +17%, P < 0.05). Propafenone (Ic, 2.6 x 10(-6) M) showed this effect only in the atrium (APD90 +33%; P < 0.01). With the faster stimulation rate of 2.5 Hz we could not find a significant influence of any drug on the APD90 in the ventricle and only quinidine prolonged the APD90 in the atrium by 16% (P < 0.05). The subclassification of Class I antiarrhythmic drugs that is based on APD modifying influences is only valid under normal heart rates (1.0 Hz). During tachycardia these actions are absent and the phenomenon of \"reverse use dependence\" is found in Class I drugs. Therefore, an additional antiarrhythmic effect due to APD modification by the examined drugs should not be expected at rapid heart rates."} {"id": "PMID:1279607", "title": "Frequency dependent effects of d-sotalol and amiodarone on the action potential duration of the human right ventricle.", "content": "Frequency dependent effects of d-Sotalol (2.0 mg/kg IV, n = 6) and amiodarone (400 mg/day for 3 months, n = 9) were studied on the action potential duration (APD) in 14 patients who underwent electrophysiological testing. Monophasic action potentials were recorded from the right ventricle at five different steady-state paced cycle lengths (700 msec, 600 msec, 500 msec, 400 msec, and 350 msec), and during ventricular extrastimuli with coupling intervals between 300 msec and 1000 msec, before and after d-sotalol and amiodarone, respectively. D-sotalol caused a prolongation of the APD at slow steady-state stimulation rates (11 +/- 5% at cycle length of 700 msec), which became attenuated at faster cycle lengths (5 +/- 3% at cycle length of 350 msec). Prolongation of APD after amiodarone was independent of pacing rate, e.g., 12 +/- 9% at cycle length of 700 msec, and 11 +/- 6% at cycle length of 350 msec. Similar frequency dependent prolongation of the APD was observed during abrupt changes of cycle lengths after d-sotalol, whereas amiodarone caused uniform prolongation of the APD at different extrastimulus intervals. Thus, d-sotalol, a nonselective potassium channel blocker, has reverse use-dependent effects on the human ventricular APD, while amiodarone with greater potassium channel selectivity, has equal ability to prolong the ventricular APD at fast and slow heart rates.", "contents": "Frequency dependent effects of d-sotalol and amiodarone on the action potential duration of the human right ventricle. Frequency dependent effects of d-Sotalol (2.0 mg/kg IV, n = 6) and amiodarone (400 mg/day for 3 months, n = 9) were studied on the action potential duration (APD) in 14 patients who underwent electrophysiological testing. Monophasic action potentials were recorded from the right ventricle at five different steady-state paced cycle lengths (700 msec, 600 msec, 500 msec, 400 msec, and 350 msec), and during ventricular extrastimuli with coupling intervals between 300 msec and 1000 msec, before and after d-sotalol and amiodarone, respectively. D-sotalol caused a prolongation of the APD at slow steady-state stimulation rates (11 +/- 5% at cycle length of 700 msec), which became attenuated at faster cycle lengths (5 +/- 3% at cycle length of 350 msec). Prolongation of APD after amiodarone was independent of pacing rate, e.g., 12 +/- 9% at cycle length of 700 msec, and 11 +/- 6% at cycle length of 350 msec. Similar frequency dependent prolongation of the APD was observed during abrupt changes of cycle lengths after d-sotalol, whereas amiodarone caused uniform prolongation of the APD at different extrastimulus intervals. Thus, d-sotalol, a nonselective potassium channel blocker, has reverse use-dependent effects on the human ventricular APD, while amiodarone with greater potassium channel selectivity, has equal ability to prolong the ventricular APD at fast and slow heart rates."} {"id": "PMID:1279608", "title": "Dual chamber rate responsive pacing to allow sotalol therapy for ventricular tachycardia.", "content": "In order to allow the use of sotalol to control ventricular tachycardia (VT), dual chamber rate responsive (DDDR) pacemakers were implanted in ten patients aged 6 to 73 years (mean 50 years). Nine presented with monomorphic VT (seven inducible at baseline electrophysiological study [EPS]) and one with syncope (monomorphic VT at EPS). On sotalol, VT was initiated in only one. This patient received sotalol in the absence of an effective alternative agent. The mean dose was 468 +/- 269 mg/day. Indications for pacing were symptomatic sotalol induced bradycardia (7), sinus node dysfunction (1), postoperative complete heart block (1), and infra-His block at baseline EPS (1). At least five of these patients would have been candidates for an implantable cardioverter defibrillator had sotalol required discontinuation. Initially, nine patients were paced in DDDR mode and one, with normal AV conduction on sotalol, in AAIR. One patient was unable to tolerate sotalol despite pacing. One patient died suddenly after 35 months of symptom-free follow-up. There was a significant improvement in symptomatic status (P = 0.03) after pacing among the other eight patients with no recurrence of VT. The implantation of a DDDR pacemaker may be indicated in selected patients with serious cardiac arrhythmias. With such a device programmed to an appropriate mode, sotalol can be used successfully where otherwise contraindicated by bradycardia or preexisting conduction disease. For some patients this may obviate the expense, inconvenience, and attendant risks of implantable cardioverter defibrillator implantation.", "contents": "Dual chamber rate responsive pacing to allow sotalol therapy for ventricular tachycardia. In order to allow the use of sotalol to control ventricular tachycardia (VT), dual chamber rate responsive (DDDR) pacemakers were implanted in ten patients aged 6 to 73 years (mean 50 years). Nine presented with monomorphic VT (seven inducible at baseline electrophysiological study [EPS]) and one with syncope (monomorphic VT at EPS). On sotalol, VT was initiated in only one. This patient received sotalol in the absence of an effective alternative agent. The mean dose was 468 +/- 269 mg/day. Indications for pacing were symptomatic sotalol induced bradycardia (7), sinus node dysfunction (1), postoperative complete heart block (1), and infra-His block at baseline EPS (1). At least five of these patients would have been candidates for an implantable cardioverter defibrillator had sotalol required discontinuation. Initially, nine patients were paced in DDDR mode and one, with normal AV conduction on sotalol, in AAIR. One patient was unable to tolerate sotalol despite pacing. One patient died suddenly after 35 months of symptom-free follow-up. There was a significant improvement in symptomatic status (P = 0.03) after pacing among the other eight patients with no recurrence of VT. The implantation of a DDDR pacemaker may be indicated in selected patients with serious cardiac arrhythmias. With such a device programmed to an appropriate mode, sotalol can be used successfully where otherwise contraindicated by bradycardia or preexisting conduction disease. For some patients this may obviate the expense, inconvenience, and attendant risks of implantable cardioverter defibrillator implantation."} {"id": "PMID:1279609", "title": "Atrial fibrillation in Wolff-Parkinson-White syndrome: reversal of isoproterenol effects by sotalol.", "content": "Sotalol has Class II and III antiarrhythmic effects. Its efficacy and safety as a treatment of atrial fibrillation in patients with the Wolff-Parkinson-White (WPW) syndrome is controversial. We evaluated the effects of isoproterenol and IV sotalol (1.5 mg/kg in 10 minutes) given together versus isoproterenol alone on anterograde conduction through the AV node and accessory pathway. Atrial fibrillation was induced in 22 patients with WPW (13 men, 9 women, 36 +/- 16 years old). AV node and accessory pathway conduction were both enhanced by isoproterenol, although the effect was greater on the AV node. The minimum interval between preexcited QRS complexes shortened in all patients. Conversely, sotalol caused a significant prolongation of the shortest preexcited QRS interval as well as of the shortest interval between narrow QRS complexes. In addition, sotalol reversed all the effects of isoproterenol during atrial fibrillation. The percent of preexcited QRS complexes was not significantly modified because variations in ventricular preexcitation results from a balance between the relative effects on refractoriness of the accessory pathway versus of the AV node and in the amount of respective anterograde and retrograde concealed conduction. There were no serious adverse effects. Reversion to sinus rhythm was documented in 12 patients (60%). These short-term observations suggest that sotalol may be safe and effective in the treatment of patients with WPW and atrial fibrillation.", "contents": "Atrial fibrillation in Wolff-Parkinson-White syndrome: reversal of isoproterenol effects by sotalol. Sotalol has Class II and III antiarrhythmic effects. Its efficacy and safety as a treatment of atrial fibrillation in patients with the Wolff-Parkinson-White (WPW) syndrome is controversial. We evaluated the effects of isoproterenol and IV sotalol (1.5 mg/kg in 10 minutes) given together versus isoproterenol alone on anterograde conduction through the AV node and accessory pathway. Atrial fibrillation was induced in 22 patients with WPW (13 men, 9 women, 36 +/- 16 years old). AV node and accessory pathway conduction were both enhanced by isoproterenol, although the effect was greater on the AV node. The minimum interval between preexcited QRS complexes shortened in all patients. Conversely, sotalol caused a significant prolongation of the shortest preexcited QRS interval as well as of the shortest interval between narrow QRS complexes. In addition, sotalol reversed all the effects of isoproterenol during atrial fibrillation. The percent of preexcited QRS complexes was not significantly modified because variations in ventricular preexcitation results from a balance between the relative effects on refractoriness of the accessory pathway versus of the AV node and in the amount of respective anterograde and retrograde concealed conduction. There were no serious adverse effects. Reversion to sinus rhythm was documented in 12 patients (60%). These short-term observations suggest that sotalol may be safe and effective in the treatment of patients with WPW and atrial fibrillation."} {"id": "PMID:1279610", "title": "Prediction of antiarrhythmic efficacy of class I and III agents in patients with ventricular tachycardia by signal-averaged ECG analysis.", "content": "The effects of procainamide and dofetilide (pure Class III antiarrhythmic agent) on the signal-averaged ECG (SAECG) were examined in relation to the results of programmed ventricular stimulation studies in 25 patients with inducible sustained monomorphic ventricular tachycardia. Procainamide prolonged significantly the total QRS and low amplitude signal durations (140 +/- 31 msec vs 166 +/- 48 msec, P < 0.0001; 50 +/- 25 msec vs 65 +/- 38 msec, P < 0.002, respectively) whereas the root mean square voltage of the last 40 msec of the QRS complex was significantly reduced (22 +/- 21 microV vs 13 +/- 12 microV, P < 0.006). Procainamide was effective (prevention of the inducibility of sustained ventricular tachycardia or prolongation of the cycle length of ventricular tachycardia by > 100 msec) in 15 of 27 drug trials. Of the procainamide induced SAECG changes, the fractional prolongation of the total QRS duration was the best parameter that identified effectively treated patients (24% +/- 16% in responders vs 10% +/- 11% in nonresponders, P < 0.014). A fractional prolongation of the total QRS duration by > 15% identified effectively treated patients with a sensitivity of 87%, specificity of 81%, and an overall predictive accuracy of 84%. Dofetilide did not change the SAECG, and no SAECG parameter predicted the results of programmed ventricular stimulation. The effects of both drugs on the spectral analysis (area ratios) and on the spectral temporal mapping (the values of normality factor) of the SAECG were not consistent. In conclusion, antiarrhythmic efficacy of procainamide can be predicted by the degree of drug induced prolongation of the signal-averaged QRS complex.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Prediction of antiarrhythmic efficacy of class I and III agents in patients with ventricular tachycardia by signal-averaged ECG analysis. The effects of procainamide and dofetilide (pure Class III antiarrhythmic agent) on the signal-averaged ECG (SAECG) were examined in relation to the results of programmed ventricular stimulation studies in 25 patients with inducible sustained monomorphic ventricular tachycardia. Procainamide prolonged significantly the total QRS and low amplitude signal durations (140 +/- 31 msec vs 166 +/- 48 msec, P < 0.0001; 50 +/- 25 msec vs 65 +/- 38 msec, P < 0.002, respectively) whereas the root mean square voltage of the last 40 msec of the QRS complex was significantly reduced (22 +/- 21 microV vs 13 +/- 12 microV, P < 0.006). Procainamide was effective (prevention of the inducibility of sustained ventricular tachycardia or prolongation of the cycle length of ventricular tachycardia by > 100 msec) in 15 of 27 drug trials. Of the procainamide induced SAECG changes, the fractional prolongation of the total QRS duration was the best parameter that identified effectively treated patients (24% +/- 16% in responders vs 10% +/- 11% in nonresponders, P < 0.014). A fractional prolongation of the total QRS duration by > 15% identified effectively treated patients with a sensitivity of 87%, specificity of 81%, and an overall predictive accuracy of 84%. Dofetilide did not change the SAECG, and no SAECG parameter predicted the results of programmed ventricular stimulation. The effects of both drugs on the spectral analysis (area ratios) and on the spectral temporal mapping (the values of normality factor) of the SAECG were not consistent. In conclusion, antiarrhythmic efficacy of procainamide can be predicted by the degree of drug induced prolongation of the signal-averaged QRS complex.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279611", "title": "Comparison of verapamil and diltiazem in the suppression of idiopathic ventricular tachycardia.", "content": "This study examines the efficacy of verapamil and diltiazem in the suppression of idiopathic ventricular tachycardia (VT). Eight patients (mean age 29.8 +/- 12.3 years, two males and six females) with VT, without any underlying cardiac abnormality on clinical examination and noninvasive investigation, were studied. The inducibility of the clinical VT was examined by treadmill exercise testing and programmed ventricular stimulation (PVS). In six patients, VT was inducible by exercise testing and in the remaining two by PVS. Following baseline testing, verapamil (120-mg thrice daily) and diltiazem (60-mg thrice daily) were administered in random order, allowing 5 half-lives for the drug to load before evaluation. Two patients had complete suppression of the VT and the remaining six patients demonstrated a partial response to both calcium antagonists. In the patients with a partial response, the duration of the longest run of VT was reduced (baseline 96.0, 34.2 SEM); verapamil 19.2 (7.5); diltiazem 45.3 (21.4 beats), whereas, there was no change in the rate of VT (baseline 199.7 (8.0); verapamil 184.5 (11.4); diltiazem 201.0 (9.5 beats/min). No proarrhythmic effect was observed with either of the drugs in these patients. We conclude that idiopathic VT can be suppressed in some patients by calcium antagonists. In patients with a partial response, the length of run of the VT can be reduced, but the rate is unaffected. Verapamil and diltiazem do not differ in their ability to suppress VT in individual patients.", "contents": "Comparison of verapamil and diltiazem in the suppression of idiopathic ventricular tachycardia. This study examines the efficacy of verapamil and diltiazem in the suppression of idiopathic ventricular tachycardia (VT). Eight patients (mean age 29.8 +/- 12.3 years, two males and six females) with VT, without any underlying cardiac abnormality on clinical examination and noninvasive investigation, were studied. The inducibility of the clinical VT was examined by treadmill exercise testing and programmed ventricular stimulation (PVS). In six patients, VT was inducible by exercise testing and in the remaining two by PVS. Following baseline testing, verapamil (120-mg thrice daily) and diltiazem (60-mg thrice daily) were administered in random order, allowing 5 half-lives for the drug to load before evaluation. Two patients had complete suppression of the VT and the remaining six patients demonstrated a partial response to both calcium antagonists. In the patients with a partial response, the duration of the longest run of VT was reduced (baseline 96.0, 34.2 SEM); verapamil 19.2 (7.5); diltiazem 45.3 (21.4 beats), whereas, there was no change in the rate of VT (baseline 199.7 (8.0); verapamil 184.5 (11.4); diltiazem 201.0 (9.5 beats/min). No proarrhythmic effect was observed with either of the drugs in these patients. We conclude that idiopathic VT can be suppressed in some patients by calcium antagonists. In patients with a partial response, the length of run of the VT can be reduced, but the rate is unaffected. Verapamil and diltiazem do not differ in their ability to suppress VT in individual patients."} {"id": "PMID:1279612", "title": "Acute and chronic electrophysiological effects of pentisomide on the sinus and AV nodal function, noninvasive evaluation by a pacemaker with temporary pacing inhibition.", "content": "The acute and chronic electrophysiological effects on sinus function and AV nodal conduction of pentisomide (Pen), a new antiarrhythmic agent, were studied in ten patients with sick sinus syndrome (SSS) (group I) and in ten patients with normal sinus function (group II) using a permanent pacemaker with temporary pacing inhibition (Symbios 7005 Medtronic, Inc.). We measured noninvasively the corrected sinus node recovery time (CSNRT), the sino-atrial conduction time (SACT), according to Narula's method and the Wenckebach point before and after Pen administration, acutely and orally for 10 days. In group I intravenous injection (4 mg/kg) and oral administration (450 mg bid) of Pen significantly prolonged the CSNRT (+217% and +149%, respectively) and the SACT (+63% and +49%, respectively). In group II only the intravenous injection of Pen provoked a significant modification of CSNRT (+12%) and SACT (+14%). No modification in AV nodal conduction was noted in any patient. These results suggest that Pen must be used with caution in patients with sinus nodal dysfunction.", "contents": "Acute and chronic electrophysiological effects of pentisomide on the sinus and AV nodal function, noninvasive evaluation by a pacemaker with temporary pacing inhibition. The acute and chronic electrophysiological effects on sinus function and AV nodal conduction of pentisomide (Pen), a new antiarrhythmic agent, were studied in ten patients with sick sinus syndrome (SSS) (group I) and in ten patients with normal sinus function (group II) using a permanent pacemaker with temporary pacing inhibition (Symbios 7005 Medtronic, Inc.). We measured noninvasively the corrected sinus node recovery time (CSNRT), the sino-atrial conduction time (SACT), according to Narula's method and the Wenckebach point before and after Pen administration, acutely and orally for 10 days. In group I intravenous injection (4 mg/kg) and oral administration (450 mg bid) of Pen significantly prolonged the CSNRT (+217% and +149%, respectively) and the SACT (+63% and +49%, respectively). In group II only the intravenous injection of Pen provoked a significant modification of CSNRT (+12%) and SACT (+14%). No modification in AV nodal conduction was noted in any patient. These results suggest that Pen must be used with caution in patients with sinus nodal dysfunction."} {"id": "PMID:1279613", "title": "Mexiletine and propafenone: a comparative study of monotherapy, low, and full dose combination therapy.", "content": "The electrophysiological effects of combination therapy of mexiletine and propafenone were assessed using standard 12-lead electrocardiogram (standard ECG), signal-averaged ECG (SAECG), and ambulatory ECG in 31 patients with ventricular arrhythmias. All patients underwent mexiletine monotherapy (M-mono), propafenone monotherapy (P-mono), low dose combination therapy (low M+P), and full dose combination therapy (full M+P). Full M+P increased the PQ interval and QRS duration to the same extent as P-mono did. Low M+P increased PQ interval and QRS duration to a lesser extent than P-mono and full M+P did. P-mono and full M+P significantly decreased root mean square (RMS) and increased f-QRS in SAECG, while M-mono and low M+P showed only a weak trend. SAECGs with late potentials increased in number with treatments; 9 in predrug control, 11 on M-mono, 15 on P-mono, 10 on low M+P, and 14 on full M+P. The percent suppression of frequent premature ventricular contractions (PVCs) (> 1,000/day) with M-mono, P-mono, low M+P, and full M+P were 46.4 +/- 9.0, 56.6 +/- 10.4, 64.4 +/- 9.2, and 71.4 +/- 7.1, respectively, and those of frequent couplets (> 10/day) were 58.3 +/- 17.7, 62.6 +/- 23.6, 87.5 +/- 6.2, and 92.1 +/- 4.0, respectively. Thus, full dose combination of mexiletine and propafenone exhibited the maximum antiarrhythmic efficacy without enhancement of effects on standard ECG and SAECG. Low dose combination therapy showed better antiarrhythmic efficacy in association with lesser effects on standard ECG and SAECG compared with propafenone monotherapy.", "contents": "Mexiletine and propafenone: a comparative study of monotherapy, low, and full dose combination therapy. The electrophysiological effects of combination therapy of mexiletine and propafenone were assessed using standard 12-lead electrocardiogram (standard ECG), signal-averaged ECG (SAECG), and ambulatory ECG in 31 patients with ventricular arrhythmias. All patients underwent mexiletine monotherapy (M-mono), propafenone monotherapy (P-mono), low dose combination therapy (low M+P), and full dose combination therapy (full M+P). Full M+P increased the PQ interval and QRS duration to the same extent as P-mono did. Low M+P increased PQ interval and QRS duration to a lesser extent than P-mono and full M+P did. P-mono and full M+P significantly decreased root mean square (RMS) and increased f-QRS in SAECG, while M-mono and low M+P showed only a weak trend. SAECGs with late potentials increased in number with treatments; 9 in predrug control, 11 on M-mono, 15 on P-mono, 10 on low M+P, and 14 on full M+P. The percent suppression of frequent premature ventricular contractions (PVCs) (> 1,000/day) with M-mono, P-mono, low M+P, and full M+P were 46.4 +/- 9.0, 56.6 +/- 10.4, 64.4 +/- 9.2, and 71.4 +/- 7.1, respectively, and those of frequent couplets (> 10/day) were 58.3 +/- 17.7, 62.6 +/- 23.6, 87.5 +/- 6.2, and 92.1 +/- 4.0, respectively. Thus, full dose combination of mexiletine and propafenone exhibited the maximum antiarrhythmic efficacy without enhancement of effects on standard ECG and SAECG. Low dose combination therapy showed better antiarrhythmic efficacy in association with lesser effects on standard ECG and SAECG compared with propafenone monotherapy."} {"id": "PMID:1279614", "title": "Antiarrhythmic efficacy of ethacizine assessed by programmed electrical stimulation in patients with ventricular tachycardia.", "content": "The efficacy of ethacizine, a Class Ic drug, was assessed by programmed electrical stimulation (PES), delivering single, double, and triple extrastimuli at paced drives of 100 and 140 beats/min from two right ventricular sites (apex and outflow tract) in 38 patients with recurrent sustained ventricular tachycardia (VT). Underlying disease was coronary artery disease (CAD) in 26 (group I) and other conditions in 12 patients (group II; hypertrophic cardiomyopathy in 7, mitral valve prolapse in 1, and no apparent heart disease in 4). In the baseline study VT was induced in all patients. After a single intravenous dose (0.6-0.7 mg/kg) of ethacizine, VT was still inducible in six patients in group I and seven patients in group II. Ethacizine was administered on a long-term basis to all patients in a dose of 200-400 mg per day. All but one CAD patient remained free of recurrences after a mean follow-up of 16.5 (range 3-22) months, while there were recurrences in six of 12 patients in group II. We conclude that: (1) ethacizine appears to be effective in the treatment of VT in CAD patients; (2) the study demonstrates the clinical utility of PES in the management of VT, although some patients in whom VT remains inducible on ethacizine may have good clinical outcome; and (3) the efficacy of ethacizine in other forms of heart disease remains to be studied.", "contents": "Antiarrhythmic efficacy of ethacizine assessed by programmed electrical stimulation in patients with ventricular tachycardia. The efficacy of ethacizine, a Class Ic drug, was assessed by programmed electrical stimulation (PES), delivering single, double, and triple extrastimuli at paced drives of 100 and 140 beats/min from two right ventricular sites (apex and outflow tract) in 38 patients with recurrent sustained ventricular tachycardia (VT). Underlying disease was coronary artery disease (CAD) in 26 (group I) and other conditions in 12 patients (group II; hypertrophic cardiomyopathy in 7, mitral valve prolapse in 1, and no apparent heart disease in 4). In the baseline study VT was induced in all patients. After a single intravenous dose (0.6-0.7 mg/kg) of ethacizine, VT was still inducible in six patients in group I and seven patients in group II. Ethacizine was administered on a long-term basis to all patients in a dose of 200-400 mg per day. All but one CAD patient remained free of recurrences after a mean follow-up of 16.5 (range 3-22) months, while there were recurrences in six of 12 patients in group II. We conclude that: (1) ethacizine appears to be effective in the treatment of VT in CAD patients; (2) the study demonstrates the clinical utility of PES in the management of VT, although some patients in whom VT remains inducible on ethacizine may have good clinical outcome; and (3) the efficacy of ethacizine in other forms of heart disease remains to be studied."} {"id": "PMID:1279615", "title": "Electrogram patterns predictive of successful radiofrequency catheter ablation of accessory pathways.", "content": "We assessed anterograde conduction electrogram parameters at successful ablation sites according to accessory pathway (AP) location and compared them to the most favorable electrograms at unsuccessful sites. A median of three radiofrequency energy impulses was applied to ablate 97% of 136 APs versus four impulses to ablate 90% of 65 concealed APs. Electrograms at successful sites showed variable A/V ratio (0.04-7), and a QS pattern of unipolar ventricular wave in 90%. Electrograms were different in right versus left AP: AV time 29 +/- 7 versus 38 +/- 10; and timing of ventricular deflection: 17 +/- 9 versus 2 +/- 9 msec, respectively. Analysis in each patient of the mapping parameters at successful versus \"most favorable\" unsuccessful sites showed an improvement in at least one parameter in 55%, no apparent change in all parameter values in 30%, and even less favorable parameters in 15% of patients. In patients with manifest AP, overall comparison of electrograms at successful versus unsuccessful sites showed no difference in A/V ratio (1.3 +/- 1.5 vs 1.2 +/- 1.6), unipolar pattern distribution, and AV time (34 +/- 10 vs 35 +/- 9), but earlier bipolar main ventricular potential (-4 +/- 12 vs -1.5 +/- 10 msec) and unipolar intrinsic deflection timings (-5.2 +/- 11 vs -1.8 +/- 10 msec). In patients with concealed AP, a retrograde continuous electrical activity was recorded in 72% of successful versus 38% of unsuccessful sites (P = 0.03). Electrogram characteristics at successful radiofrequency ablation are different in right and left manifest AP.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Electrogram patterns predictive of successful radiofrequency catheter ablation of accessory pathways. We assessed anterograde conduction electrogram parameters at successful ablation sites according to accessory pathway (AP) location and compared them to the most favorable electrograms at unsuccessful sites. A median of three radiofrequency energy impulses was applied to ablate 97% of 136 APs versus four impulses to ablate 90% of 65 concealed APs. Electrograms at successful sites showed variable A/V ratio (0.04-7), and a QS pattern of unipolar ventricular wave in 90%. Electrograms were different in right versus left AP: AV time 29 +/- 7 versus 38 +/- 10; and timing of ventricular deflection: 17 +/- 9 versus 2 +/- 9 msec, respectively. Analysis in each patient of the mapping parameters at successful versus \"most favorable\" unsuccessful sites showed an improvement in at least one parameter in 55%, no apparent change in all parameter values in 30%, and even less favorable parameters in 15% of patients. In patients with manifest AP, overall comparison of electrograms at successful versus unsuccessful sites showed no difference in A/V ratio (1.3 +/- 1.5 vs 1.2 +/- 1.6), unipolar pattern distribution, and AV time (34 +/- 10 vs 35 +/- 9), but earlier bipolar main ventricular potential (-4 +/- 12 vs -1.5 +/- 10 msec) and unipolar intrinsic deflection timings (-5.2 +/- 11 vs -1.8 +/- 10 msec). In patients with concealed AP, a retrograde continuous electrical activity was recorded in 72% of successful versus 38% of unsuccessful sites (P = 0.03). Electrogram characteristics at successful radiofrequency ablation are different in right and left manifest AP.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279616", "title": "Separation of ventricular tachycardia from sinus rhythm using a practical, real-time template matching computer system.", "content": "Template matching morphology analysis of the intraventricular electrogram (IVEG) has been proposed for inclusion in implantable cardioverter defibrillators (ICDs) to reduce the number of false ventricular tachyarrhythmia detections caused by rate overlap between ventricular tachycardia (VT) and sinus tachycardia and/or supraventricular tachycardia. Template matching techniques have been developed that reduce the computational complexity while preserving the perceived important aspects of electrogram amplitude and baseline independence found in such computationally unsolved methods as correlation waveform analysis (CWA). These methods have been shown to work as well as CWA for separation of VT, however, they have not been proven in real-time on a system that incorporates many of the constraints of present day ICDs. The present study was undertaken with two purposes: (1) to determine if real-time IVEG template matching analysis on an ICD sensing emulator was accurate in separating VT from sinus rhythm (SR) electrograms; and (2) to compare amplitude normalized area of difference (NAD) with signature analysis (SIG), a new, computationally less expensive technique that normalizes for amplitude variation within the expected physiological level of variability. In this study, IVEGs, obtained from 16 patients who underwent electrophysiological study (EPS) for evaluation of sustained ventricular arrhythmia, were digitized to 250 Hz with 6-bit quantization after filtering (16-44 Hz) and differentiation. After an SR template was selected and periodically updated, it was compared to subsequent IVEGs using NAD and SIG. In general, SIG calculates the fraction of samples occurring outside template window boundaries. Eleven-beat running medians from beat-by-beat NAD and SIG results were determined.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Separation of ventricular tachycardia from sinus rhythm using a practical, real-time template matching computer system. Template matching morphology analysis of the intraventricular electrogram (IVEG) has been proposed for inclusion in implantable cardioverter defibrillators (ICDs) to reduce the number of false ventricular tachyarrhythmia detections caused by rate overlap between ventricular tachycardia (VT) and sinus tachycardia and/or supraventricular tachycardia. Template matching techniques have been developed that reduce the computational complexity while preserving the perceived important aspects of electrogram amplitude and baseline independence found in such computationally unsolved methods as correlation waveform analysis (CWA). These methods have been shown to work as well as CWA for separation of VT, however, they have not been proven in real-time on a system that incorporates many of the constraints of present day ICDs. The present study was undertaken with two purposes: (1) to determine if real-time IVEG template matching analysis on an ICD sensing emulator was accurate in separating VT from sinus rhythm (SR) electrograms; and (2) to compare amplitude normalized area of difference (NAD) with signature analysis (SIG), a new, computationally less expensive technique that normalizes for amplitude variation within the expected physiological level of variability. In this study, IVEGs, obtained from 16 patients who underwent electrophysiological study (EPS) for evaluation of sustained ventricular arrhythmia, were digitized to 250 Hz with 6-bit quantization after filtering (16-44 Hz) and differentiation. After an SR template was selected and periodically updated, it was compared to subsequent IVEGs using NAD and SIG. In general, SIG calculates the fraction of samples occurring outside template window boundaries. Eleven-beat running medians from beat-by-beat NAD and SIG results were determined.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279617", "title": "Ventricular tachycardia detection using bipolar electrogram analysis is site specific.", "content": "While algorithms for bipolar intraventricular electrogram analysis have potential use in complementing rate criteria for ventricular tachycardia (VT) detection by implantable antitachycardia devices, the sensitivity of such algorithms to the intracavitary site of electrogram detection has not been determined. In this study, unfiltered (1-500 Hz) electrograms were recorded from a bipolar electrode catheter initially positioned at the right ventricular (RV) apex (site 1) of 12 patients during sinus rhythm (SR1) and during induced monomorphic VT (VT1). Sinus rhythm (SR2) and the identical VT (VT2) were recorded a second time after repositioning the same electrode catheter within the RV apex (site 2) 7-44 mm (mean +/- SD = 15 +/- 10) from its original site. The data were digitized at 1,000 Hz. Templates from SR1 and SR2, respectively, were compared subsequently with individual intraventricular electrograms from 15-25 sec passages of SR1 and VT1 and SR2 and VT2, respectively, using correlation waveform analysis. At site 1, the mean patient correlation coefficient ranged from 0.982-0.998 during SR1 and 0.062-0.975 during VT1. At site 2, the mean patient correlation coefficient ranged from 0.995-0.998 during SR2 and 0.113-0.983 during VT2. Using a correlation threshold of 0.9, VT was differentiated from SR in 11/12 patients (91%) overall: 8/12 patients (67%) at site 1, 9/12 patients (75%) at site 2, and 6/12 patients (50%) at both sites. Thus, while discrimination of VT from SR is feasible with morphological analysis of bipolar right ventricular intracavitary electrograms, the accuracy of bipolar intraventricular electrogram analysis may depend upon intracavitary electrode location in selected patients.", "contents": "Ventricular tachycardia detection using bipolar electrogram analysis is site specific. While algorithms for bipolar intraventricular electrogram analysis have potential use in complementing rate criteria for ventricular tachycardia (VT) detection by implantable antitachycardia devices, the sensitivity of such algorithms to the intracavitary site of electrogram detection has not been determined. In this study, unfiltered (1-500 Hz) electrograms were recorded from a bipolar electrode catheter initially positioned at the right ventricular (RV) apex (site 1) of 12 patients during sinus rhythm (SR1) and during induced monomorphic VT (VT1). Sinus rhythm (SR2) and the identical VT (VT2) were recorded a second time after repositioning the same electrode catheter within the RV apex (site 2) 7-44 mm (mean +/- SD = 15 +/- 10) from its original site. The data were digitized at 1,000 Hz. Templates from SR1 and SR2, respectively, were compared subsequently with individual intraventricular electrograms from 15-25 sec passages of SR1 and VT1 and SR2 and VT2, respectively, using correlation waveform analysis. At site 1, the mean patient correlation coefficient ranged from 0.982-0.998 during SR1 and 0.062-0.975 during VT1. At site 2, the mean patient correlation coefficient ranged from 0.995-0.998 during SR2 and 0.113-0.983 during VT2. Using a correlation threshold of 0.9, VT was differentiated from SR in 11/12 patients (91%) overall: 8/12 patients (67%) at site 1, 9/12 patients (75%) at site 2, and 6/12 patients (50%) at both sites. Thus, while discrimination of VT from SR is feasible with morphological analysis of bipolar right ventricular intracavitary electrograms, the accuracy of bipolar intraventricular electrogram analysis may depend upon intracavitary electrode location in selected patients."} {"id": "PMID:1279619", "title": "Role of early afterdepolarization in familial long QTU syndrome and torsade de pointes.", "content": "Torsade de pointes (TdP) syncopal episodes were almost invariably precipitated by emotional stress or menstruation in a 17-year-old girl. U wave accentuation occurred during sinus rhythm without pauses in periods of heightened sympathetic tone. To examine the role of early afterdepolarization (EAD), monophasic action potentials were recorded during ventricular extrasystoles and TdP occurring spontaneously and induced by ventricular pacing. The effects of lidocaine, verapamil, propranolol, and epinephrine were assessed. Our data show that: (1) EAD plays a significant role in the genesis of familial long QTU syndrome and TdP; (2) rapid ventricular pacing causes postpause-dependent EADs, U waves, and TdP; and (3) EAD is enhanced by epinephrine infusion in the absence of pause, whereas EAD-triggered firing is inhibited by verapamil and propranolol but not by lidocaine.", "contents": "Role of early afterdepolarization in familial long QTU syndrome and torsade de pointes. Torsade de pointes (TdP) syncopal episodes were almost invariably precipitated by emotional stress or menstruation in a 17-year-old girl. U wave accentuation occurred during sinus rhythm without pauses in periods of heightened sympathetic tone. To examine the role of early afterdepolarization (EAD), monophasic action potentials were recorded during ventricular extrasystoles and TdP occurring spontaneously and induced by ventricular pacing. The effects of lidocaine, verapamil, propranolol, and epinephrine were assessed. Our data show that: (1) EAD plays a significant role in the genesis of familial long QTU syndrome and TdP; (2) rapid ventricular pacing causes postpause-dependent EADs, U waves, and TdP; and (3) EAD is enhanced by epinephrine infusion in the absence of pause, whereas EAD-triggered firing is inhibited by verapamil and propranolol but not by lidocaine."} {"id": "PMID:1279620", "title": "Survival after a first episode of ventricular tachycardia or fibrillation.", "content": "Recent outcome analyses in ventricular tachycardia (VT) and ventricular fibrillation (VF) have included patients undergoing electrophysiological study (EPS) at tertiary care centers. The selection process involved could introduce bias in the reported populations. We analyzed the outcome of 42 consecutive patients (aged 63 +/- 11 years) admitted to a coronary care unit within 48 hours of a first episode of VT/VF not associated with reversible causes. All patients recovered neurologically and were candidates for EPS. Nine patients (21%) died during the initial hospitalization (none had EPS), and another nine died during a follow-up of 17 +/- 12 months. Actuarial survival at 1 and 2 years was 64% and 62%, respectively. By Cox's model, congestive heart failure functional Class III-IV (P = 0.008; hazard ratio = 3.7) was the only independent prognostic factor. Among patients discharged, subsequent survival did not depend on the performance of EPS or on the antiarrhythmic therapeutic modalities used. Mortality after a first episode of VT/VF is high. Severe congestive heart failure is the most powerful prognostic factor. Studies including successfully referred patients undergoing EPS may not reflect the true natural history of patients with VT/VF.", "contents": "Survival after a first episode of ventricular tachycardia or fibrillation. Recent outcome analyses in ventricular tachycardia (VT) and ventricular fibrillation (VF) have included patients undergoing electrophysiological study (EPS) at tertiary care centers. The selection process involved could introduce bias in the reported populations. We analyzed the outcome of 42 consecutive patients (aged 63 +/- 11 years) admitted to a coronary care unit within 48 hours of a first episode of VT/VF not associated with reversible causes. All patients recovered neurologically and were candidates for EPS. Nine patients (21%) died during the initial hospitalization (none had EPS), and another nine died during a follow-up of 17 +/- 12 months. Actuarial survival at 1 and 2 years was 64% and 62%, respectively. By Cox's model, congestive heart failure functional Class III-IV (P = 0.008; hazard ratio = 3.7) was the only independent prognostic factor. Among patients discharged, subsequent survival did not depend on the performance of EPS or on the antiarrhythmic therapeutic modalities used. Mortality after a first episode of VT/VF is high. Severe congestive heart failure is the most powerful prognostic factor. Studies including successfully referred patients undergoing EPS may not reflect the true natural history of patients with VT/VF."} {"id": "PMID:1279621", "title": "Changes in ventricular effective refractory periods after two extrastimuli and ventricular electrical instability.", "content": "Using programmed stimulation with one and three extrastimuli delivered in the right ventricular apex, we compared the effective refractory period (ERP) during sinus rhythm (ERP-SR) and during the third extrastimulus (ERP-S3) in patients without ventricular tachycardias (control group, n = 87) and in patients with documented ventricular tachycardia (VT group, n = 76). The protocol was not completed to determine ERP-S3 in one patient in the control group and in 15 patients in the VT group. We observed a significantly greater change (i.e., shortening) in ERP after two extrastimuli in the VT group compared with patients without VT (delta ERP = 45 +/- 20 msec in the control group and 70 +/- 16 msec in the VT group, P < 0.001). This electrophysiological phenomenon, along with conduction delay, may play an important role in VT induction.", "contents": "Changes in ventricular effective refractory periods after two extrastimuli and ventricular electrical instability. Using programmed stimulation with one and three extrastimuli delivered in the right ventricular apex, we compared the effective refractory period (ERP) during sinus rhythm (ERP-SR) and during the third extrastimulus (ERP-S3) in patients without ventricular tachycardias (control group, n = 87) and in patients with documented ventricular tachycardia (VT group, n = 76). The protocol was not completed to determine ERP-S3 in one patient in the control group and in 15 patients in the VT group. We observed a significantly greater change (i.e., shortening) in ERP after two extrastimuli in the VT group compared with patients without VT (delta ERP = 45 +/- 20 msec in the control group and 70 +/- 16 msec in the VT group, P < 0.001). This electrophysiological phenomenon, along with conduction delay, may play an important role in VT induction."} {"id": "PMID:1279622", "title": "Programmed electrical stimulation protocols: variations on a theme.", "content": "A series of prospective protocols were designed to determine the yield ratio (true positives vs. false positives = nonclinical) in various patient groups using a variety of programmed electrical stimulation (PES) variables. First, a PES protocol was used in 772 patients. Single, double, and triple extrastimuli were delivered in sequence (leaving each successive extrastimulus just beyond its refractory period before moving to the next extrastimulus) during sinus rhythm and two ventricular paced rates at the RV apex, before moving to the outflow tract and repeating the sequence and then moving on to isoproterenol infusion with the PES sequence repeated at the apex. This protocol met NASPE standards for induction of VT in patients with coronary artery disease and a history of VT, while failing to induce monomorphic VT in any control patient. The best yield ratios combined with the greatest likelihood of inducing clinical tachycardia were achieved with sinus rhythm and three extrastimuli, and pacing at the lower rate and three extrastimuli. Pacing at the faster rate and triple extrastimuli was highly inductive of clinical arrhythmias, but had a low yield ratio due to induction of more nonclinical arrhythmias than other steps. The next protocol was performed in 61 patients with inducible ventricular tachycardia. In each case, the protocol described above was completed at the RV apex, even if tachycardia was also induced at an earlier point in the protocol. This allowed for more accurate yield ratios to be established for each step in the protocol, since each patient was exposed to each of these steps.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Programmed electrical stimulation protocols: variations on a theme. A series of prospective protocols were designed to determine the yield ratio (true positives vs. false positives = nonclinical) in various patient groups using a variety of programmed electrical stimulation (PES) variables. First, a PES protocol was used in 772 patients. Single, double, and triple extrastimuli were delivered in sequence (leaving each successive extrastimulus just beyond its refractory period before moving to the next extrastimulus) during sinus rhythm and two ventricular paced rates at the RV apex, before moving to the outflow tract and repeating the sequence and then moving on to isoproterenol infusion with the PES sequence repeated at the apex. This protocol met NASPE standards for induction of VT in patients with coronary artery disease and a history of VT, while failing to induce monomorphic VT in any control patient. The best yield ratios combined with the greatest likelihood of inducing clinical tachycardia were achieved with sinus rhythm and three extrastimuli, and pacing at the lower rate and three extrastimuli. Pacing at the faster rate and triple extrastimuli was highly inductive of clinical arrhythmias, but had a low yield ratio due to induction of more nonclinical arrhythmias than other steps. The next protocol was performed in 61 patients with inducible ventricular tachycardia. In each case, the protocol described above was completed at the RV apex, even if tachycardia was also induced at an earlier point in the protocol. This allowed for more accurate yield ratios to be established for each step in the protocol, since each patient was exposed to each of these steps.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279623", "title": "Phase plane plot of electrograms as a marker of ventricular electrical instability during acute ischemia: initial experimental results and potential clinical applications.", "content": "We used a phase plane plots method (a plot of voltage [V(t)] vs rate of change of voltage [dV/dt]) derived from nonlinear dynamics to transform a sinus rhythm strip into a geometric form. The geometric form thus obtained detects variations in the ECG over time and therefore may aid in identifying patterns of vulnerability to ventricular fibrillation (VF). The trajectories of consecutive ventricular depolarizations and repolarizations of sinus rhythm in dogs that evolve to VF showed characteristic differential band thickening (inhomogeneities) that were absent in the dogs that did not develop VF. This method of analysis can be a useful complementary tool to detect cardiac electrical instability, and with simple hardware, can easily be displayed in real time.", "contents": "Phase plane plot of electrograms as a marker of ventricular electrical instability during acute ischemia: initial experimental results and potential clinical applications. We used a phase plane plots method (a plot of voltage [V(t)] vs rate of change of voltage [dV/dt]) derived from nonlinear dynamics to transform a sinus rhythm strip into a geometric form. The geometric form thus obtained detects variations in the ECG over time and therefore may aid in identifying patterns of vulnerability to ventricular fibrillation (VF). The trajectories of consecutive ventricular depolarizations and repolarizations of sinus rhythm in dogs that evolve to VF showed characteristic differential band thickening (inhomogeneities) that were absent in the dogs that did not develop VF. This method of analysis can be a useful complementary tool to detect cardiac electrical instability, and with simple hardware, can easily be displayed in real time."} {"id": "PMID:1279624", "title": "Increased temporo-spatial dispersion of repolarization during double premature stimulation in the intact ventricle.", "content": "The degree of temporo-spatial variation of repolarization during single (S2) and double (S3) premature stimulation was evaluated in five closed-chest anesthetized dogs. Monophasic action potentials (MAP) were simultaneously recorded with contact electrode and MAP duration (MAPD) restitution curves constructed from right ventricular (RV) and left ventricular (LV) endocardial sites. At a given coupling interval, S3 was associated with significantly greater dispersion of MAPD then S2 (spatial dispersion, i.e., between RV and LV). Similarly, at a given diastolic interval, S3 at RV and LV sites, was associated with significantly greater dispersion of MAPD then S2 (temporal dispersion). It is concluded that S3 is associated with greater temporo-spatial dispersion of repolarization then S2.", "contents": "Increased temporo-spatial dispersion of repolarization during double premature stimulation in the intact ventricle. The degree of temporo-spatial variation of repolarization during single (S2) and double (S3) premature stimulation was evaluated in five closed-chest anesthetized dogs. Monophasic action potentials (MAP) were simultaneously recorded with contact electrode and MAP duration (MAPD) restitution curves constructed from right ventricular (RV) and left ventricular (LV) endocardial sites. At a given coupling interval, S3 was associated with significantly greater dispersion of MAPD then S2 (spatial dispersion, i.e., between RV and LV). Similarly, at a given diastolic interval, S3 at RV and LV sites, was associated with significantly greater dispersion of MAPD then S2 (temporal dispersion). It is concluded that S3 is associated with greater temporo-spatial dispersion of repolarization then S2."} {"id": "PMID:1279625", "title": "Autonomic manipulation influences both temporal and frequency analyses of late potentials.", "content": "Previous studies of late potentials have not standardized the autonomic milieu at the time of testing. We studied the effects of autonomic manipulation in seven patients with previous Q wave myocardial infarction. Late potentials were evaluated using standard temporal (TD) and spectral temporal mapping techniques (STM) in the drug free state, and during separate intravenous administration of each of the following: isoproterenol, esmolol, and atropine. Isoproterenol was titrated to achieve a heart rate of 130% of baseline. Esmolol was infused at a rate of 250 micrograms/kg per minute, after a loading dose of 500 micrograms/kg. Atropine was given as a 2-mg bolus. In addition, five patients who received no drug infusions acted as controls, undergoing four serial signal-averaging studies in the baseline state: a \"baseline\" study, and then three additional studies at time intervals similar to those incurred by the study patients. Therefore, a total of 21 TD and 21 STM tests were done in the study group (seven patients; three drugs per patient) during the drug infusions, and 15 TD and 15 STM tests were done in the control group (five patients; three \"nonbaseline\" tests per patient). A change (normal to abnormal, or vice versa) in TD during a drug infusion occurred in 24% of the tests. No such change occurred in the control group (P < 0.01). A change in STM during a drug infusion occurred in 38% of tests, versus 13% of tests in the control group (P = 0.14). Overall, six of seven patients had a change in TD and/or STM diagnosis with infusion of one or more of the study drugs.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Autonomic manipulation influences both temporal and frequency analyses of late potentials. Previous studies of late potentials have not standardized the autonomic milieu at the time of testing. We studied the effects of autonomic manipulation in seven patients with previous Q wave myocardial infarction. Late potentials were evaluated using standard temporal (TD) and spectral temporal mapping techniques (STM) in the drug free state, and during separate intravenous administration of each of the following: isoproterenol, esmolol, and atropine. Isoproterenol was titrated to achieve a heart rate of 130% of baseline. Esmolol was infused at a rate of 250 micrograms/kg per minute, after a loading dose of 500 micrograms/kg. Atropine was given as a 2-mg bolus. In addition, five patients who received no drug infusions acted as controls, undergoing four serial signal-averaging studies in the baseline state: a \"baseline\" study, and then three additional studies at time intervals similar to those incurred by the study patients. Therefore, a total of 21 TD and 21 STM tests were done in the study group (seven patients; three drugs per patient) during the drug infusions, and 15 TD and 15 STM tests were done in the control group (five patients; three \"nonbaseline\" tests per patient). A change (normal to abnormal, or vice versa) in TD during a drug infusion occurred in 24% of the tests. No such change occurred in the control group (P < 0.01). A change in STM during a drug infusion occurred in 38% of tests, versus 13% of tests in the control group (P = 0.14). Overall, six of seven patients had a change in TD and/or STM diagnosis with infusion of one or more of the study drugs.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279626", "title": "Relationship between spectral measures of heart rate variability and ventricular ectopic activity in patients with idiopathic ventricular tachycardia.", "content": "This study examines the relationship of hourly spectral measures of heart rate variability (HRV) to the occurrence of ventricular ectopic (VE) activity in 20 patients with idiopathic ventricular tachycardia and frequent VE's. Spectral measures of HRV were obtained from 24-hour Holter recordings from the patients in a drug free state and included the total energies in the spectrum, the low frequency components (L) (0.04-0.15 Hz) representing predominantly sympathetic tone with some contribution from the parasympathetic and high frequency components (H) (0.15-0.4 Hz) representing mainly parasympathetic tone. A high H component (parasympathetic) was defined as area > 12 msec and high L components (sympathetic) as area > 30 msec. On an hourly analysis of spectral components in relation to VE activity, VE's occurred significantly more frequently during periods of low H and low L (F = 20.5, DF = 3, P < 0.0001). The number of VE's did not differ statistically in the other combinations of H and L components (low H, low L = 612.8 (50.1); high H, low L = 180.1 (36.8); low H, high L = 338.4 (58.9); high H, high L = 204.9 (17.7) VE's/hr (SEM). The results suggest that VE's are more frequent during periods of low H and low L and are diminished when either H or L are increased in patients with idiopathic ventricular tachycardia. The results would be consistent with the hypothesis that the parasympathetic nervous system has an electrophysiologically stabilizing effect on the myocardium.", "contents": "Relationship between spectral measures of heart rate variability and ventricular ectopic activity in patients with idiopathic ventricular tachycardia. This study examines the relationship of hourly spectral measures of heart rate variability (HRV) to the occurrence of ventricular ectopic (VE) activity in 20 patients with idiopathic ventricular tachycardia and frequent VE's. Spectral measures of HRV were obtained from 24-hour Holter recordings from the patients in a drug free state and included the total energies in the spectrum, the low frequency components (L) (0.04-0.15 Hz) representing predominantly sympathetic tone with some contribution from the parasympathetic and high frequency components (H) (0.15-0.4 Hz) representing mainly parasympathetic tone. A high H component (parasympathetic) was defined as area > 12 msec and high L components (sympathetic) as area > 30 msec. On an hourly analysis of spectral components in relation to VE activity, VE's occurred significantly more frequently during periods of low H and low L (F = 20.5, DF = 3, P < 0.0001). The number of VE's did not differ statistically in the other combinations of H and L components (low H, low L = 612.8 (50.1); high H, low L = 180.1 (36.8); low H, high L = 338.4 (58.9); high H, high L = 204.9 (17.7) VE's/hr (SEM). The results suggest that VE's are more frequent during periods of low H and low L and are diminished when either H or L are increased in patients with idiopathic ventricular tachycardia. The results would be consistent with the hypothesis that the parasympathetic nervous system has an electrophysiologically stabilizing effect on the myocardium."} {"id": "PMID:1279627", "title": "Intraindividual reproducibility of heart rate variability.", "content": "Heart rate variability was determined from three consecutive Holter recordings performed on days 1, 7, and 28 in 17 normal subjects, in 13 patients with angiographically normal coronary arteries, and in 9 patients with remote myocardial infarctions. Group data of several time and frequency domain measures of heart rate variability were highly reproducible (correlation coefficients 0.629-0.894). However, some individuals exhibited considerably larger day-to-day variations in heart rate variability. Single heart rate indices differed by up to 50% between two Holter recordings. Such potential differences must be considered when repeated heart rate variability determinations are used to assess changes in neurocardiac reflex regulation or effects of therapeutic interventions.", "contents": "Intraindividual reproducibility of heart rate variability. Heart rate variability was determined from three consecutive Holter recordings performed on days 1, 7, and 28 in 17 normal subjects, in 13 patients with angiographically normal coronary arteries, and in 9 patients with remote myocardial infarctions. Group data of several time and frequency domain measures of heart rate variability were highly reproducible (correlation coefficients 0.629-0.894). However, some individuals exhibited considerably larger day-to-day variations in heart rate variability. Single heart rate indices differed by up to 50% between two Holter recordings. Such potential differences must be considered when repeated heart rate variability determinations are used to assess changes in neurocardiac reflex regulation or effects of therapeutic interventions."} {"id": "PMID:1279628", "title": "Prognostic value of heart rate variability in patients awaiting cardiac transplantation.", "content": "Time and frequency domain parameters of heart rate variability (HRV) were determined in patients with severe endstage heart failure awaiting cardiac transplantation (HTX). These parameters were then correlated with mortality to investigate the performance of HRV in discriminating between groups with high and low risk of death. The standard deviation of five consecutive RR intervals (SDANN) was found to be the parameter with the greatest sensitivity (90%) and specificity (91%). Patients with SDANN values of < 55 msec had a twenty-fold increased risk of death (90% confidence limits: 4-118, P < 0.001). The results furthermore suggest that measurements of HRV are superior to other prognostic markers such as left ventricular ejection fraction, pulmonary artery wedge pressure, cardiac index, and serum sodium levels. We conclude that HRV is a powerful, noninvasive tool to assess the risk of death in candidates for HTX. HRV measurements can therefore be used as a supplement to other markers of risk to determine the optimal therapeutic strategy in patients with severe congestive heart failure.", "contents": "Prognostic value of heart rate variability in patients awaiting cardiac transplantation. Time and frequency domain parameters of heart rate variability (HRV) were determined in patients with severe endstage heart failure awaiting cardiac transplantation (HTX). These parameters were then correlated with mortality to investigate the performance of HRV in discriminating between groups with high and low risk of death. The standard deviation of five consecutive RR intervals (SDANN) was found to be the parameter with the greatest sensitivity (90%) and specificity (91%). Patients with SDANN values of < 55 msec had a twenty-fold increased risk of death (90% confidence limits: 4-118, P < 0.001). The results furthermore suggest that measurements of HRV are superior to other prognostic markers such as left ventricular ejection fraction, pulmonary artery wedge pressure, cardiac index, and serum sodium levels. We conclude that HRV is a powerful, noninvasive tool to assess the risk of death in candidates for HTX. HRV measurements can therefore be used as a supplement to other markers of risk to determine the optimal therapeutic strategy in patients with severe congestive heart failure."} {"id": "PMID:1279629", "title": "Heart rate variability in patients with vasovagal syndrome.", "content": "The aim of this study was to assess the heart rate variability in patients with vasovagal syndrome (VVS). Heart rate variability was expressed as: (1) the standard deviation (SD) of the mean RR interval; and (2) the SD as a percentage of the mean RR interval (%SD). Heart rate variability was measured in VVS patients and compared with control individuals. Eighteen patients (mean age 50 +/- 14 years) with a history of recurrent syncope and positive tilt testing were included in the study. Fifteen asymptomatic individuals (mean age 53 +/- 13 years) with no history of syncope and negative tilt testing were used as a control group. The SD and %SD (39 +/- 38 and 5 +/- 4 msec) in the VVS group were statistically higher at the tenth minute of tilt testing than in the control group (20 +/- 14 and 2.5 +/- 1.8 msec, P = 0.03 and P < 0.05, respectively). The mean RR interval (mean heart rate) was shorter after the 15th minute of tilt testing in the VVS group than in the control group (RR-VVS 687 +/- 136 msec, RR-control 801 +/- 131 msec, P < 0.05). It is concluded that heart rate variability, as expressed by the SD of the mean RR interval, and the SD as a percentage of the mean RR interval (%SD) are significantly higher in VVS patients than in control asymptomatic individuals.", "contents": "Heart rate variability in patients with vasovagal syndrome. The aim of this study was to assess the heart rate variability in patients with vasovagal syndrome (VVS). Heart rate variability was expressed as: (1) the standard deviation (SD) of the mean RR interval; and (2) the SD as a percentage of the mean RR interval (%SD). Heart rate variability was measured in VVS patients and compared with control individuals. Eighteen patients (mean age 50 +/- 14 years) with a history of recurrent syncope and positive tilt testing were included in the study. Fifteen asymptomatic individuals (mean age 53 +/- 13 years) with no history of syncope and negative tilt testing were used as a control group. The SD and %SD (39 +/- 38 and 5 +/- 4 msec) in the VVS group were statistically higher at the tenth minute of tilt testing than in the control group (20 +/- 14 and 2.5 +/- 1.8 msec, P = 0.03 and P < 0.05, respectively). The mean RR interval (mean heart rate) was shorter after the 15th minute of tilt testing in the VVS group than in the control group (RR-VVS 687 +/- 136 msec, RR-control 801 +/- 131 msec, P < 0.05). It is concluded that heart rate variability, as expressed by the SD of the mean RR interval, and the SD as a percentage of the mean RR interval (%SD) are significantly higher in VVS patients than in control asymptomatic individuals."} {"id": "PMID:1279630", "title": "Osmotic regulation of substance P and neurokinin A peptide content and substance P binding sites in distinct hypothalamic nuclei of the rat.", "content": "Quantitative receptor autoradiography using Bolton-Hunter iodinated substance P (SP) was used to localize specific sites in the rat hypothalamus. The amount of SP and neurokinin A (NkA) in extracts from discrete areas of the hypothalamus was measured using specific radioimmunoassays. A high density of SP binding sites was observed in the perimeter of the magnocellular paraventricular and supraoptic nuclei, while the magnocellular nuclei themselves possessed a low receptor density. In control animals, the number of SP binding sites was also low in the arcuate nucleus and the median eminence. Substance P and NkA peptide concentrations were highest in the paraventricular nucleus (PVN), decreasing in the following order: arcuate nucleus (Arc) greater than median eminence (ME) greater than supraoptic nucleus (SON) greater than subfornical organ (SFO). In animals given 340 mmol/l NaCl instead of tap water to drink for 12 days, significant increases in the number of SP binding sites occurred in the medial parvocellular subdivision of the PVN, periamygdaloid cortex, medial preoptic nucleus, Arc, and ME, but other hypothalamic areas were unaffected. In saline-treated animals, significant increases in SP and NkA peptide concentrations were observed in the ME, while in the SFO only the concentration of NkA increased significantly. In the SON, substance P and neurokinin A levels were doubled, whereas in the PVN and Arc no changes in peptide levels were observed. Chronic osmotic stimulation is associated with lowered circulating levels of adrenocorticotropin releasing hormone (ACTH), and the present data further substantiate the hypothesis that hypothalamic tachykinin-containing neuronal terminals are centrally involved in the inhibition of anterior pituitary ACTH release observed during chronic osmotic stimulation.", "contents": "Osmotic regulation of substance P and neurokinin A peptide content and substance P binding sites in distinct hypothalamic nuclei of the rat. Quantitative receptor autoradiography using Bolton-Hunter iodinated substance P (SP) was used to localize specific sites in the rat hypothalamus. The amount of SP and neurokinin A (NkA) in extracts from discrete areas of the hypothalamus was measured using specific radioimmunoassays. A high density of SP binding sites was observed in the perimeter of the magnocellular paraventricular and supraoptic nuclei, while the magnocellular nuclei themselves possessed a low receptor density. In control animals, the number of SP binding sites was also low in the arcuate nucleus and the median eminence. Substance P and NkA peptide concentrations were highest in the paraventricular nucleus (PVN), decreasing in the following order: arcuate nucleus (Arc) greater than median eminence (ME) greater than supraoptic nucleus (SON) greater than subfornical organ (SFO). In animals given 340 mmol/l NaCl instead of tap water to drink for 12 days, significant increases in the number of SP binding sites occurred in the medial parvocellular subdivision of the PVN, periamygdaloid cortex, medial preoptic nucleus, Arc, and ME, but other hypothalamic areas were unaffected. In saline-treated animals, significant increases in SP and NkA peptide concentrations were observed in the ME, while in the SFO only the concentration of NkA increased significantly. In the SON, substance P and neurokinin A levels were doubled, whereas in the PVN and Arc no changes in peptide levels were observed. Chronic osmotic stimulation is associated with lowered circulating levels of adrenocorticotropin releasing hormone (ACTH), and the present data further substantiate the hypothesis that hypothalamic tachykinin-containing neuronal terminals are centrally involved in the inhibition of anterior pituitary ACTH release observed during chronic osmotic stimulation."} {"id": "PMID:1279631", "title": "Coexistence of calcitonin gene-related peptide and galanin immunoreactivity in female rat pelvic and lumbosacral dorsal root ganglia.", "content": "Coexistence of immunoreactivity for calcitonin gene-related peptide (CGRP) and galanin (GAL) was examined in varicose nerve endings in female rat pelvic paracervical ganglia (PG) and in perikarya of lumbosacral dorsal root ganglia (DRG). Varicose peptide-containing nerves were closely adjacent to somata of neurons in the PG, certain somata being virtually surrounded by immunoreactive varicosities. Some nerve endings were immunoreactive for either CGRP or GAL; in others, immunoreactivity for CGRP and GAL coexisted. Likewise, many perikarya in DRG were CGRP immunoreactive, fewer were GAL immunoreactive, and in some immunoreactivity for CGRP and GAL coexisted. The results suggest there are subpopulations of neuropeptide-containing sensory nerve endings in the PG; some contain CGRP, some contain GAL, and in some CGRP and GAL coexist. These substances contained in sensory nerve endings could have important roles in pelvic ganglionic functions.", "contents": "Coexistence of calcitonin gene-related peptide and galanin immunoreactivity in female rat pelvic and lumbosacral dorsal root ganglia. Coexistence of immunoreactivity for calcitonin gene-related peptide (CGRP) and galanin (GAL) was examined in varicose nerve endings in female rat pelvic paracervical ganglia (PG) and in perikarya of lumbosacral dorsal root ganglia (DRG). Varicose peptide-containing nerves were closely adjacent to somata of neurons in the PG, certain somata being virtually surrounded by immunoreactive varicosities. Some nerve endings were immunoreactive for either CGRP or GAL; in others, immunoreactivity for CGRP and GAL coexisted. Likewise, many perikarya in DRG were CGRP immunoreactive, fewer were GAL immunoreactive, and in some immunoreactivity for CGRP and GAL coexisted. The results suggest there are subpopulations of neuropeptide-containing sensory nerve endings in the PG; some contain CGRP, some contain GAL, and in some CGRP and GAL coexist. These substances contained in sensory nerve endings could have important roles in pelvic ganglionic functions."} {"id": "PMID:1279632", "title": "Development of a potent bombesin receptor antagonist with prolonged in vivo inhibitory activity on bombesin-stimulated amylase and protein release in the rat.", "content": "Of the various types of potent bombesin(Bn)/gastrin releasing peptide receptor antagonists that have been discovered, the desMet14-methyl ester peptides are devoid of residual agonist activity and are among the most potent in terms of in vitro receptor blockade and also in terms of their prolonged inhibition of bombesin-stimulated amylase and protein release in the rat. We have now examined the in vitro and in vivo properties of a new series of methyl ester analogues, [D-Phe6]Bn(6-13)OMe, [D-Phe6,D-Ala11]Bn(6-13)OMe, N alpha-propionyl-[D-Ala24]GRP(20-26)OMe, and [D-pentafluoro-Phe6,D-Ala11]Bn(6-13)OMe, which have an additional D-amino acid substituent and some highly lipophilic moieties at the N-terminus. All analogues were able to potently antagonize the ability of Bn to stimulate amylase release from rat acinar cells, with IC50 values of 2.4, 2.5, 0.6, and 1.3 nM, respectively. The four peptides were found to have binding affinities for these cells comparable to Bn itself, with K(i)s of 10.3, 2.8, 5.5, and 3.6 nM, respectively, but all had little or no affinity for neuromedin B receptors on murine C6 cells. Single bolus IV injections of these peptides were found to potently inhibit amylase and protein release caused by IV infusion of bombesin into the rat. Generally the peptides containing the D-Ala substituent were longer acting than [D-Phe6]Bn(6-13)OMe, so that [D-Phe6,D-Ala11]Bn(6-13)OMe and N alpha-propionyl-[D-Ala24]GRP(20-26)OMe displayed significant inhibitory effects for up to 1.5 h after administration.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Development of a potent bombesin receptor antagonist with prolonged in vivo inhibitory activity on bombesin-stimulated amylase and protein release in the rat. Of the various types of potent bombesin(Bn)/gastrin releasing peptide receptor antagonists that have been discovered, the desMet14-methyl ester peptides are devoid of residual agonist activity and are among the most potent in terms of in vitro receptor blockade and also in terms of their prolonged inhibition of bombesin-stimulated amylase and protein release in the rat. We have now examined the in vitro and in vivo properties of a new series of methyl ester analogues, [D-Phe6]Bn(6-13)OMe, [D-Phe6,D-Ala11]Bn(6-13)OMe, N alpha-propionyl-[D-Ala24]GRP(20-26)OMe, and [D-pentafluoro-Phe6,D-Ala11]Bn(6-13)OMe, which have an additional D-amino acid substituent and some highly lipophilic moieties at the N-terminus. All analogues were able to potently antagonize the ability of Bn to stimulate amylase release from rat acinar cells, with IC50 values of 2.4, 2.5, 0.6, and 1.3 nM, respectively. The four peptides were found to have binding affinities for these cells comparable to Bn itself, with K(i)s of 10.3, 2.8, 5.5, and 3.6 nM, respectively, but all had little or no affinity for neuromedin B receptors on murine C6 cells. Single bolus IV injections of these peptides were found to potently inhibit amylase and protein release caused by IV infusion of bombesin into the rat. Generally the peptides containing the D-Ala substituent were longer acting than [D-Phe6]Bn(6-13)OMe, so that [D-Phe6,D-Ala11]Bn(6-13)OMe and N alpha-propionyl-[D-Ala24]GRP(20-26)OMe displayed significant inhibitory effects for up to 1.5 h after administration.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279633", "title": "Modulation of hypothalamic galanin gene expression by estrogen in peripubertal rats.", "content": "Hypothalamic galanin gene expression was investigated during reproductive maturation in peripubertal rats. Rat galanin-like immunoreactivity (rGAL-LI) increased in the median eminence and anterior pituitary during the extended first estrous and diestrous phases relative to anestrous phase female or male rats. In the neurointermediate lobe, rGAL-LI was elevated in first diestrous phase compared to anestrous phase females or males. In a second study, hypothalamic tissue was divided into quadrants for analysis of rat galanin (rGAL) mRNA by Northern blot hybridization. Two days after the injection of pregnant mare's serum gonadotropin (PMSG), rGAL mRNA increased approximately twofold in the paraventricular area and preoptic area quadrants. No effects of PMSG on galanin gene expression were found in medial basal or supraoptic hypothalamic quadrants. Because PMSG acts through the stimulation of ovarian estrogen secretion, these studies conclude that galanin gene expression in dorsal hypothalamic nuclei is under the stimulatory influence of estrogen and suggest that galanin may be a mediator of central ovarian steroid feedback.", "contents": "Modulation of hypothalamic galanin gene expression by estrogen in peripubertal rats. Hypothalamic galanin gene expression was investigated during reproductive maturation in peripubertal rats. Rat galanin-like immunoreactivity (rGAL-LI) increased in the median eminence and anterior pituitary during the extended first estrous and diestrous phases relative to anestrous phase female or male rats. In the neurointermediate lobe, rGAL-LI was elevated in first diestrous phase compared to anestrous phase females or males. In a second study, hypothalamic tissue was divided into quadrants for analysis of rat galanin (rGAL) mRNA by Northern blot hybridization. Two days after the injection of pregnant mare's serum gonadotropin (PMSG), rGAL mRNA increased approximately twofold in the paraventricular area and preoptic area quadrants. No effects of PMSG on galanin gene expression were found in medial basal or supraoptic hypothalamic quadrants. Because PMSG acts through the stimulation of ovarian estrogen secretion, these studies conclude that galanin gene expression in dorsal hypothalamic nuclei is under the stimulatory influence of estrogen and suggest that galanin may be a mediator of central ovarian steroid feedback."} {"id": "PMID:1279634", "title": "Intravenously infused substance P enhances basal and growth hormone (GH) releasing hormone-stimulated GH secretion in normal men.", "content": "The effect of synthetic substance P (SP), infused intravenously (IV) in doses of 0.5, 1, or 1.5 pmol/kg-1/min-1 over 60 min, on GH secretion was evaluated in seven healthy men. Substance P tests and a control test with normal saline were randomly performed at weekly intervals. No untoward side effects or changes in blood pressure were observed during SP infusions. Serum GH concentrations did not change when normal saline, the lowest dose, or the middle dose of SP were infused. In contrast, GH levels rose significantly when the highest dose of SP was given, with a mean peak two times higher than baseline. Further studies were performed to test the possible influence of SP on the GH response to GH-RH. For this purpose, seven other healthy men were tested with GH-RH (1 micrograms/kg body weight in an IV bolus) during saline or SP (1.5 pmol/Kg-1/min-1 x 60 min) infusion. The GH-RH induced a significant GH rise, with a mean peak seven times higher than baseline. When subjects were infused with SP, the GH response to GH-RH was greatly enhanced, with a mean peak 12 times higher than baseline. These results demonstrate for the first time in humans that the systemic infusion of SP stimulates GH secretion, and suggest that SP might interact with GH-RH in the stimulation of GH secretion.", "contents": "Intravenously infused substance P enhances basal and growth hormone (GH) releasing hormone-stimulated GH secretion in normal men. The effect of synthetic substance P (SP), infused intravenously (IV) in doses of 0.5, 1, or 1.5 pmol/kg-1/min-1 over 60 min, on GH secretion was evaluated in seven healthy men. Substance P tests and a control test with normal saline were randomly performed at weekly intervals. No untoward side effects or changes in blood pressure were observed during SP infusions. Serum GH concentrations did not change when normal saline, the lowest dose, or the middle dose of SP were infused. In contrast, GH levels rose significantly when the highest dose of SP was given, with a mean peak two times higher than baseline. Further studies were performed to test the possible influence of SP on the GH response to GH-RH. For this purpose, seven other healthy men were tested with GH-RH (1 micrograms/kg body weight in an IV bolus) during saline or SP (1.5 pmol/Kg-1/min-1 x 60 min) infusion. The GH-RH induced a significant GH rise, with a mean peak seven times higher than baseline. When subjects were infused with SP, the GH response to GH-RH was greatly enhanced, with a mean peak 12 times higher than baseline. These results demonstrate for the first time in humans that the systemic infusion of SP stimulates GH secretion, and suggest that SP might interact with GH-RH in the stimulation of GH secretion."} {"id": "PMID:1279640", "title": "[Myocardial infarction-related arrhythmia after rehabilitation treatment in a sanatorium].", "content": "The study involved 100 patients (80 men and 20 women), aged between 27 and 69 years treated at the Department of Cardiology, Medical Academy in Lublin for the first myocardial infarction, and classified for a 4-week rehabilitation in sanatorium. A 24-hours ECG recording with Holter technique (Medilog 3000 manufactured by Oxford Medilog Timed) was performed twice. In the first record cardiac arrhythmias ( extrasystole both supra- and ventricular, ventricular tachycardia) were more frequent in comparison with the results of the second recording carried out after a 4-week rehabilitation.", "contents": "[Myocardial infarction-related arrhythmia after rehabilitation treatment in a sanatorium]. The study involved 100 patients (80 men and 20 women), aged between 27 and 69 years treated at the Department of Cardiology, Medical Academy in Lublin for the first myocardial infarction, and classified for a 4-week rehabilitation in sanatorium. A 24-hours ECG recording with Holter technique (Medilog 3000 manufactured by Oxford Medilog Timed) was performed twice. In the first record cardiac arrhythmias ( extrasystole both supra- and ventricular, ventricular tachycardia) were more frequent in comparison with the results of the second recording carried out after a 4-week rehabilitation."} {"id": "PMID:1279641", "title": "[A case of phyto-mucous bezoar of the stomach].", "content": "A case of gastric phyto-mucous bezoar++ in an edentulous patient with chronic gastritis is reported. The effective medical treatment consisted of partial gastroscopic bezoar crumbling, gastric lavage with 1% sodium bicarbonate solution, and endoscopic removal of residual bezoar. The pathogenesis, symptoms, and treatment of gastric phytobezoars are discussed.", "contents": "[A case of phyto-mucous bezoar of the stomach]. A case of gastric phyto-mucous bezoar++ in an edentulous patient with chronic gastritis is reported. The effective medical treatment consisted of partial gastroscopic bezoar crumbling, gastric lavage with 1% sodium bicarbonate solution, and endoscopic removal of residual bezoar. The pathogenesis, symptoms, and treatment of gastric phytobezoars are discussed."} {"id": "PMID:1279642", "title": "[Evaluation of ambulatory treatment of advanced forms of Hodgkin's disease with special reference to psychological, social and economic aspects].", "content": "Patients with advanced lymphogranulomatosis were divided into two subgroups. One, including 9 patients was treated in the hospital, and the second, including 21 patients, was treated at out-patient department. Results of the treatment and its adverse reactions were not significantly different in patients treated on out-patient basis and in hospital. However, unfavourable effect of therapy on patient's psychological status (anxiety) was less expressed in out-patient conditions. Such a way of treatment enables also considerable savings related to the repeated hospitalizations.", "contents": "[Evaluation of ambulatory treatment of advanced forms of Hodgkin's disease with special reference to psychological, social and economic aspects]. Patients with advanced lymphogranulomatosis were divided into two subgroups. One, including 9 patients was treated in the hospital, and the second, including 21 patients, was treated at out-patient department. Results of the treatment and its adverse reactions were not significantly different in patients treated on out-patient basis and in hospital. However, unfavourable effect of therapy on patient's psychological status (anxiety) was less expressed in out-patient conditions. Such a way of treatment enables also considerable savings related to the repeated hospitalizations."} {"id": "PMID:1279646", "title": "The distribution of PSA, cathepsin-D, and pS2 in BPH and cancer of the prostate.", "content": "In view of the limitations associated with the present tumor markers for prostate cancer, we have examined the potential expression of two further markers, Cathepsin-D and pS2, in human prostate and attempted to link their concentrations with the histopathology of the tissue, the PSA levels and the androgenic status of the gland. Cathepsin-D and pS2 were measured in cytosol fractions obtained from 22 patients with benign prostatic hyperplasia (BPH) and 20 patients with prostate cancer (CaP) employing immunoassays specific for these markers. The concentrations of Cathepsin-D (BPH: mean +/- SEM = 18.50 +/- 1.88 nmol/g protein; CaP = 19.75 +/- 2.49 nmol/g protein) and pS2 (BPH = 1,024.7 +/- 348.06 ng/g protein; CaP = 1,513.88 +/- 268.60 ng/g protein) were not different in the two tissue types, whereas PSA in BPH tissue (1,952.27 +/- 249.93 micrograms/g protein) was significantly higher than the measurements in CaP (583.75 +/- 104.33 micrograms/g protein). However, none of the tumor marker concentrations correlated with the degree of differentiation of the tumors, and we were unable to establish any correlation with the levels of testosterone and dihydrotestosterone in the tissue. In conclusion, although Cathepsin-D and pS2 are expressed in prostate tissue, it is doubtful whether they will have an active role in the management of prostate cancer.", "contents": "The distribution of PSA, cathepsin-D, and pS2 in BPH and cancer of the prostate. In view of the limitations associated with the present tumor markers for prostate cancer, we have examined the potential expression of two further markers, Cathepsin-D and pS2, in human prostate and attempted to link their concentrations with the histopathology of the tissue, the PSA levels and the androgenic status of the gland. Cathepsin-D and pS2 were measured in cytosol fractions obtained from 22 patients with benign prostatic hyperplasia (BPH) and 20 patients with prostate cancer (CaP) employing immunoassays specific for these markers. The concentrations of Cathepsin-D (BPH: mean +/- SEM = 18.50 +/- 1.88 nmol/g protein; CaP = 19.75 +/- 2.49 nmol/g protein) and pS2 (BPH = 1,024.7 +/- 348.06 ng/g protein; CaP = 1,513.88 +/- 268.60 ng/g protein) were not different in the two tissue types, whereas PSA in BPH tissue (1,952.27 +/- 249.93 micrograms/g protein) was significantly higher than the measurements in CaP (583.75 +/- 104.33 micrograms/g protein). However, none of the tumor marker concentrations correlated with the degree of differentiation of the tumors, and we were unable to establish any correlation with the levels of testosterone and dihydrotestosterone in the tissue. In conclusion, although Cathepsin-D and pS2 are expressed in prostate tissue, it is doubtful whether they will have an active role in the management of prostate cancer."} {"id": "PMID:1279644", "title": "Bifunctional pharmacophores. Biological activities of the peptide analog containing both casomorphine-like and substance P antagonist-like active elements.", "content": "SP-antagonistic properties of a newly synthesized peptide Tyr-Pro-D-Phe-Phe-D-Phe-D-Trp-MetNH2 (AWL-60) were investigated both in vitro and in vivo. In vitro AWL-60 effectively antagonized the action of SP-agonist (SP6-11); however, this antagonism was non-competitive. Antagonistic properties of AWL-60 were also observed in vivo: in doses as low as 0.1 nmol/kg iv AWL-60 markedly attenuated the fall in blood pressure produced by [less than Glu]6SP6-11. Since AWL-60 exerts weak opioid agonistic properties (as a casomorphine analog) the possible involvement of an opioid agonistic component in their SP inhibitory action is considered.", "contents": "Bifunctional pharmacophores. Biological activities of the peptide analog containing both casomorphine-like and substance P antagonist-like active elements. SP-antagonistic properties of a newly synthesized peptide Tyr-Pro-D-Phe-Phe-D-Phe-D-Trp-MetNH2 (AWL-60) were investigated both in vitro and in vivo. In vitro AWL-60 effectively antagonized the action of SP-agonist (SP6-11); however, this antagonism was non-competitive. Antagonistic properties of AWL-60 were also observed in vivo: in doses as low as 0.1 nmol/kg iv AWL-60 markedly attenuated the fall in blood pressure produced by [less than Glu]6SP6-11. Since AWL-60 exerts weak opioid agonistic properties (as a casomorphine analog) the possible involvement of an opioid agonistic component in their SP inhibitory action is considered."} {"id": "PMID:1279647", "title": "Validation of a symptoms questionnaire for benign prostatic hyperplasia.", "content": "We developed a questionnaire to assess the effect of finasteride on symptoms of benign prostatic hyperplasia (BPH) by modifying that of Boyarsky (1977). To validate the questionnaire, a cohort study was conducted in 2 groups of patients with BPH and 3 control groups without BPH. The BPH groups were: (1) 34 patients before TURP (transurethral resection of the prostate), average age 68 years; (2) 65 patients after TURP, average age 68 years; (3) 40 patients after other nonserious nonurological surgery, average age 50 years; (4) 14 healthy non-BPH volunteers, average age 58 years; and (5) 73 healthy non-BPH volunteers, average age 37 years. The questionnaire was administered once to all subjects, and a subset responded to a second administration. Mean total symptoms scores (TSS) from the initial questioning were 6.4, 3.2, 2.9, 2.6, and 1.6 for the 5 groups, respectively (pooled SD = 3.3); mean total troublesome symptoms scores (TTSS) were 4.8, 2.1, 1.4, 1.1, and 0.6, respectively (pooled SD = 2.2). All other groups were significantly less symptomatic and troubled than the pre-TURP group, and all surgical groups were significantly more so than the younger volunteer group. These data demonstrate the discriminant validity of the questionnaire. Corroborating prior data [Gregg et al., 1990], responsiveness was shown by the 3.7-point mean TSS improvement in response to TURP, which was significantly different from the near-zero changes in the other groups. Reproducibility was shown by kappa statistics being nearly all greater than 0.75 and an intraclass correlation coefficient of 0.64; construct validity and reliability were demonstrated by correlation (r = 0.7) with a general urination problems question; and internal consistency was documented by Cronbach's alpha values of approximately 0.6. We conclude that this questionnaire is a useful and validated tool for assessing BPH symptoms.", "contents": "Validation of a symptoms questionnaire for benign prostatic hyperplasia. We developed a questionnaire to assess the effect of finasteride on symptoms of benign prostatic hyperplasia (BPH) by modifying that of Boyarsky (1977). To validate the questionnaire, a cohort study was conducted in 2 groups of patients with BPH and 3 control groups without BPH. The BPH groups were: (1) 34 patients before TURP (transurethral resection of the prostate), average age 68 years; (2) 65 patients after TURP, average age 68 years; (3) 40 patients after other nonserious nonurological surgery, average age 50 years; (4) 14 healthy non-BPH volunteers, average age 58 years; and (5) 73 healthy non-BPH volunteers, average age 37 years. The questionnaire was administered once to all subjects, and a subset responded to a second administration. Mean total symptoms scores (TSS) from the initial questioning were 6.4, 3.2, 2.9, 2.6, and 1.6 for the 5 groups, respectively (pooled SD = 3.3); mean total troublesome symptoms scores (TTSS) were 4.8, 2.1, 1.4, 1.1, and 0.6, respectively (pooled SD = 2.2). All other groups were significantly less symptomatic and troubled than the pre-TURP group, and all surgical groups were significantly more so than the younger volunteer group. These data demonstrate the discriminant validity of the questionnaire. Corroborating prior data [Gregg et al., 1990], responsiveness was shown by the 3.7-point mean TSS improvement in response to TURP, which was significantly different from the near-zero changes in the other groups. Reproducibility was shown by kappa statistics being nearly all greater than 0.75 and an intraclass correlation coefficient of 0.64; construct validity and reliability were demonstrated by correlation (r = 0.7) with a general urination problems question; and internal consistency was documented by Cronbach's alpha values of approximately 0.6. We conclude that this questionnaire is a useful and validated tool for assessing BPH symptoms."} {"id": "PMID:1279645", "title": "Synthesis and biological activity in the GPI test of scyliorhinin I and its Val7 and Ile7 analogs.", "content": "Scyliorhinin I, a decapeptide, of tachykinin family, and its two analogs containing Val or Ile in position 7, have been synthesized using the solid-phase method, and tested for agonistic activity on isolated guinea pig ileum. Both analogs were slightly more active than scyliorhinin I, but they were significantly less potent than substance P.", "contents": "Synthesis and biological activity in the GPI test of scyliorhinin I and its Val7 and Ile7 analogs. Scyliorhinin I, a decapeptide, of tachykinin family, and its two analogs containing Val or Ile in position 7, have been synthesized using the solid-phase method, and tested for agonistic activity on isolated guinea pig ileum. Both analogs were slightly more active than scyliorhinin I, but they were significantly less potent than substance P."} {"id": "PMID:1279648", "title": "Dynamic changes in the intermediate filaments of the epithelial cells during development of the chicken's bursa of Fabricius.", "content": "The development of bursal follicles and the differentiation of the follicle-associated epithelium and interfollicular epithelium were studied immunohistochemically using monoclonal anti-vimentin and anti-cytokeratin antibodies. In 10-day-old embryos the entodermal and cloacal epithelia coexpressed vimentin- and cytokeratin-intermediate filaments. Both undifferentiated and differentiated bursal surface epithelium simultaneously expressed vimentin- and cytokeratin-intermediate filaments during the entire period of embryogenesis. Vimentin expression in reticuloepithelial cells was related to bursal cell differentiation but was not linked to immune function. Sequential loss of vimentin from interfollicular epithelium, follicle-associated epithelium, and reticuloepithelial cells may reflect sequential acquisition of maturity in these three compartments. The presence of cytokeratin-intermediate filaments suggested that follicle-associated epithelium was not of mesenchymal origin. Testosterone treatment did not influence the vimentin and cytokeratin filament expression in the epithelial cell.", "contents": "Dynamic changes in the intermediate filaments of the epithelial cells during development of the chicken's bursa of Fabricius. The development of bursal follicles and the differentiation of the follicle-associated epithelium and interfollicular epithelium were studied immunohistochemically using monoclonal anti-vimentin and anti-cytokeratin antibodies. In 10-day-old embryos the entodermal and cloacal epithelia coexpressed vimentin- and cytokeratin-intermediate filaments. Both undifferentiated and differentiated bursal surface epithelium simultaneously expressed vimentin- and cytokeratin-intermediate filaments during the entire period of embryogenesis. Vimentin expression in reticuloepithelial cells was related to bursal cell differentiation but was not linked to immune function. Sequential loss of vimentin from interfollicular epithelium, follicle-associated epithelium, and reticuloepithelial cells may reflect sequential acquisition of maturity in these three compartments. The presence of cytokeratin-intermediate filaments suggested that follicle-associated epithelium was not of mesenchymal origin. Testosterone treatment did not influence the vimentin and cytokeratin filament expression in the epithelial cell."} {"id": "PMID:1279650", "title": "Reversal of signs of induced cotton effects of dicumarol-alpha 1-acid glycoprotein systems by phenothiazine neuroleptics through ternary complexation.", "content": "The interaction of dicumarol and phenothiazine neuroleptics binding to alpha 1-acid glycoprotein (AGP) was investigated by circular dichroism (CD) and equilibrium dialysis. The induced CD spectra of the dicumarol-AGP complex were affected differently by the different substituents of the phenothiazine molecule. The sign of the induced Cotton effect of dicumarol bound to AGP was reversibly changed with the introduction of the propyldimethylamine substituent at position 10 or chloride group at position 2 of the phenothiazine molecule. Chlorpromazine, which contains both of these substituents reversed the sign of the induced Cotton effect with the highest intensity. The addition of trifluoperazine, fluphenazine, and promethazine containing neither of the two substituents generated a new negative CD band. However, the addition of opromazine, which contains sulfoxide at position 5, decreased the CD intensity of the dicumarol-AGP complex without changing the shape of the CD spectra. Equilibrium dialysis studies revealed that the interaction of dicumarol-AGP with phenothiazine derivatives occurred simultaneously, and the interaction followed a cooperative and anticooperative binding model. Further, among the six phenothiazine derivatives that reversed the signs of the induced Cotton effects of the dicumarol-AGP complex, a linear relationship was observed between coupling constants and the difference in the induced optical ellipticity. The opromazine and dicumarol interaction was competitive for a common binding site on the AGP molecule. Removal of sialic acid did not have any effect on this interaction. These data support the hypothesis that the acidic and the basic drug binding sites overlap each other.", "contents": "Reversal of signs of induced cotton effects of dicumarol-alpha 1-acid glycoprotein systems by phenothiazine neuroleptics through ternary complexation. The interaction of dicumarol and phenothiazine neuroleptics binding to alpha 1-acid glycoprotein (AGP) was investigated by circular dichroism (CD) and equilibrium dialysis. The induced CD spectra of the dicumarol-AGP complex were affected differently by the different substituents of the phenothiazine molecule. The sign of the induced Cotton effect of dicumarol bound to AGP was reversibly changed with the introduction of the propyldimethylamine substituent at position 10 or chloride group at position 2 of the phenothiazine molecule. Chlorpromazine, which contains both of these substituents reversed the sign of the induced Cotton effect with the highest intensity. The addition of trifluoperazine, fluphenazine, and promethazine containing neither of the two substituents generated a new negative CD band. However, the addition of opromazine, which contains sulfoxide at position 5, decreased the CD intensity of the dicumarol-AGP complex without changing the shape of the CD spectra. Equilibrium dialysis studies revealed that the interaction of dicumarol-AGP with phenothiazine derivatives occurred simultaneously, and the interaction followed a cooperative and anticooperative binding model. Further, among the six phenothiazine derivatives that reversed the signs of the induced Cotton effects of the dicumarol-AGP complex, a linear relationship was observed between coupling constants and the difference in the induced optical ellipticity. The opromazine and dicumarol interaction was competitive for a common binding site on the AGP molecule. Removal of sialic acid did not have any effect on this interaction. These data support the hypothesis that the acidic and the basic drug binding sites overlap each other."} {"id": "PMID:1279649", "title": "Nedocromil sodium modulates the function of long-term rat peritoneal mast cell cultures.", "content": "Long-term rat peritoneal mast cell (MC) cultures consisting of MC co-cultured with 3T3 fibroblasts (MC/3T3) were employed to study the effects of repeated and prolonged incubation with nedocromil sodium (10(-3) and 10(-5) M) on MC activation. When nedocromil sodium was added simultaneously with compound 48/80 to MC/3T3 on the first day of the experiment, it inhibited histamine release to the same extent as when added to the cultures a week later upon rechallenge. In other experiments activated MC/3T3 were incubated with nedocromil sodium for a week and on the last day of the experiment fresh nedocromil sodium was added simultaneously with compound 48/80. Under these conditions the drug was as potent in inhibiting histamine release from the activated MC as it was in cultures incubated for a week with medium alone. In addition, preincubation of naive MC with nedocromil sodium for two days inhibited histamine release from these cells when activated for the first time. Salbutamol (10(-3) and 10(-5) M) exhibited a similar inhibitory effect to nedocromil sodium upon simultaneous incubation with MC/3T3. However, prolonged incubation of salbutamol with MC/3T3 cultures resulted in tachyphylaxis. We conclude that nedocromil sodium is an effective MC stabilizing drug since it similarly inhibits histamine release from both primarily and secondarily challenged MC. Moreover this drug does not lose its efficacy upon prolonged incubation with MC.", "contents": "Nedocromil sodium modulates the function of long-term rat peritoneal mast cell cultures. Long-term rat peritoneal mast cell (MC) cultures consisting of MC co-cultured with 3T3 fibroblasts (MC/3T3) were employed to study the effects of repeated and prolonged incubation with nedocromil sodium (10(-3) and 10(-5) M) on MC activation. When nedocromil sodium was added simultaneously with compound 48/80 to MC/3T3 on the first day of the experiment, it inhibited histamine release to the same extent as when added to the cultures a week later upon rechallenge. In other experiments activated MC/3T3 were incubated with nedocromil sodium for a week and on the last day of the experiment fresh nedocromil sodium was added simultaneously with compound 48/80. Under these conditions the drug was as potent in inhibiting histamine release from the activated MC as it was in cultures incubated for a week with medium alone. In addition, preincubation of naive MC with nedocromil sodium for two days inhibited histamine release from these cells when activated for the first time. Salbutamol (10(-3) and 10(-5) M) exhibited a similar inhibitory effect to nedocromil sodium upon simultaneous incubation with MC/3T3. However, prolonged incubation of salbutamol with MC/3T3 cultures resulted in tachyphylaxis. We conclude that nedocromil sodium is an effective MC stabilizing drug since it similarly inhibits histamine release from both primarily and secondarily challenged MC. Moreover this drug does not lose its efficacy upon prolonged incubation with MC."} {"id": "PMID:1279651", "title": "Multiple oral administration of a ketoprofen-dextran ester prodrug in pigs: assessment of gastrointestinal bioavailability by deconvolution.", "content": "Deconvolution has been applied to estimate the in vivo dissolution/release process of ketoprofen from a ketoprofen-dextran ester prodrug in pigs. The prodrug was given to three pigs at intervals of 12 hr and in seven doses corresponding to 4 mg ketoprofen/kg body weight. Frequent blood sampling was carried out at the first, third, and seventh intervals. Plasma steady-state concentrations of ketoprofen following the prodrug administration were between 2 and 4 micrograms/ml. The reference consisted of a single p.o. dose of parent ketoprofen (4 mg/kg body weight). For each pig the response following the multiple dosing was deconvolved with the reference response using an algebraic deconvolution procedure adopted from the literature. The obtained cumulated in vivo dissolution/release profiles revealed similar release rates for the three pigs and similar extents of release (59, 70, and 65%). The mean in vivo dissolution/release times (MDT) were calculated to be 5.4, 6.1, and 5.7 hr, respectively. In conclusion, following administration of the dextran prodrug the plasma concentration curves and the dissolution/release profiles are uniform, with small interindividual variations.", "contents": "Multiple oral administration of a ketoprofen-dextran ester prodrug in pigs: assessment of gastrointestinal bioavailability by deconvolution. Deconvolution has been applied to estimate the in vivo dissolution/release process of ketoprofen from a ketoprofen-dextran ester prodrug in pigs. The prodrug was given to three pigs at intervals of 12 hr and in seven doses corresponding to 4 mg ketoprofen/kg body weight. Frequent blood sampling was carried out at the first, third, and seventh intervals. Plasma steady-state concentrations of ketoprofen following the prodrug administration were between 2 and 4 micrograms/ml. The reference consisted of a single p.o. dose of parent ketoprofen (4 mg/kg body weight). For each pig the response following the multiple dosing was deconvolved with the reference response using an algebraic deconvolution procedure adopted from the literature. The obtained cumulated in vivo dissolution/release profiles revealed similar release rates for the three pigs and similar extents of release (59, 70, and 65%). The mean in vivo dissolution/release times (MDT) were calculated to be 5.4, 6.1, and 5.7 hr, respectively. In conclusion, following administration of the dextran prodrug the plasma concentration curves and the dissolution/release profiles are uniform, with small interindividual variations."} {"id": "PMID:1279652", "title": "Interactions between substance P and norepinephrine in the regulation of nociception in mouse spinal cord.", "content": "This study examined interactions between effects of the undecapeptide substance P and norepinephrine and the alpha-adrenoceptor agonist clonidine in the mouse spinal cord. All compounds were injected into the lumbar subarachnoid space, and effects on the tail-flick reflex and the behavioural response to intrathecal substance P were evaluated. The tail-flick response latencies were markedly increased 5-20 min. after intrathecal application of norepinephrine (0.0125-0.1 microgram) or clonidine (0.0125-0.1 microgram). The actions of both intrathecal norepinephrine (0.025 microgram) and intrathecal clonidine (0.025 microgram) were significantly attenuated when substance P (5 micrograms) was given intrathecally 55 and 45 min. before the agonists. There was a significant relationship between the tail-flick response latencies and the tail skin temperature. However, the tail-flick results were not due to changes in the skin temperature. Intrathecally applied substance P (10 ng) produced a response consisting of biting of the caudal part of the body and a few hindlimb scratches. The number of bites was significantly reduced 5 min. after injection of norepinephrine (0.1 micrograms) or clonidine (0.05-0.1 microgram), but the number of scratches was unchanged. The data show that increased stimulation of spinal alpha-adrenoceptors inhibits a spinal nociceptive reflex as well as the action of substance P in the spinal cord. Substance P modulates the action of alpha-adrenoceptor agonists on the tail-flick reflex, which may tentatively be explained by downregulation of alpha-adrenoceptors by substance P.", "contents": "Interactions between substance P and norepinephrine in the regulation of nociception in mouse spinal cord. This study examined interactions between effects of the undecapeptide substance P and norepinephrine and the alpha-adrenoceptor agonist clonidine in the mouse spinal cord. All compounds were injected into the lumbar subarachnoid space, and effects on the tail-flick reflex and the behavioural response to intrathecal substance P were evaluated. The tail-flick response latencies were markedly increased 5-20 min. after intrathecal application of norepinephrine (0.0125-0.1 microgram) or clonidine (0.0125-0.1 microgram). The actions of both intrathecal norepinephrine (0.025 microgram) and intrathecal clonidine (0.025 microgram) were significantly attenuated when substance P (5 micrograms) was given intrathecally 55 and 45 min. before the agonists. There was a significant relationship between the tail-flick response latencies and the tail skin temperature. However, the tail-flick results were not due to changes in the skin temperature. Intrathecally applied substance P (10 ng) produced a response consisting of biting of the caudal part of the body and a few hindlimb scratches. The number of bites was significantly reduced 5 min. after injection of norepinephrine (0.1 micrograms) or clonidine (0.05-0.1 microgram), but the number of scratches was unchanged. The data show that increased stimulation of spinal alpha-adrenoceptors inhibits a spinal nociceptive reflex as well as the action of substance P in the spinal cord. Substance P modulates the action of alpha-adrenoceptor agonists on the tail-flick reflex, which may tentatively be explained by downregulation of alpha-adrenoceptors by substance P."} {"id": "PMID:1279653", "title": "Ouabain enhancement of compound 48/80 induced histamine secretion from rat peritoneal mast cells: dependence on extracellular sodium.", "content": "Purified populations of rat peritoneal mast cells were used to study the effect of ouabain on compound 48/80-induced histamine secretion and on 86Rb+ uptake. 86Rb+ was used as a tracer for extracellular K+. The calculated value of the ouabain-sensitive uptake of K+ and 86Rb+ was considered a measure of the Na(+)-K+ pump activity of the cells. Ouabain caused an immediate inhibition of the pump activity and a time-dependent increase in histamine secretion in the absence of extracellular calcium. No effect on the secretion was observed in the presence of calcium. The effect of ouabain on the secretion occurs in the presence of sodium but not when sodium was replaced by lithium. Preservation by ouabain of a high intracellular sodium content in sodium-loaded cells was associated with preservation of the secretory response in a calcium-free medium. In the presence of lanthanum in a calcium-free medium, the pump activity was inhibited and the enhancement by ouabain of the secretion of histamine was blocked. A less marked inhibition of the pump was found in a calcium-free medium containing magnesium. The inhibition exerted by magnesium was concentration-dependent (0-5 mM) as was the counteraction of magnesium of the enhancement of ouabain of the secretion of histamine. These observations indicate that the enhancement by ouabain of the secretory response of mast cells preincubated in a calcium-free medium is associated with accumulation of sodium inside the cell. In addition to a decreased rate of sodium-calcium exchange caused by a decreased inward directed sodium gradient, the mechanism by which ouabain enhances the secretory response is likely to involve an increased binding of calcium to membrane binding sites.", "contents": "Ouabain enhancement of compound 48/80 induced histamine secretion from rat peritoneal mast cells: dependence on extracellular sodium. Purified populations of rat peritoneal mast cells were used to study the effect of ouabain on compound 48/80-induced histamine secretion and on 86Rb+ uptake. 86Rb+ was used as a tracer for extracellular K+. The calculated value of the ouabain-sensitive uptake of K+ and 86Rb+ was considered a measure of the Na(+)-K+ pump activity of the cells. Ouabain caused an immediate inhibition of the pump activity and a time-dependent increase in histamine secretion in the absence of extracellular calcium. No effect on the secretion was observed in the presence of calcium. The effect of ouabain on the secretion occurs in the presence of sodium but not when sodium was replaced by lithium. Preservation by ouabain of a high intracellular sodium content in sodium-loaded cells was associated with preservation of the secretory response in a calcium-free medium. In the presence of lanthanum in a calcium-free medium, the pump activity was inhibited and the enhancement by ouabain of the secretion of histamine was blocked. A less marked inhibition of the pump was found in a calcium-free medium containing magnesium. The inhibition exerted by magnesium was concentration-dependent (0-5 mM) as was the counteraction of magnesium of the enhancement of ouabain of the secretion of histamine. These observations indicate that the enhancement by ouabain of the secretory response of mast cells preincubated in a calcium-free medium is associated with accumulation of sodium inside the cell. In addition to a decreased rate of sodium-calcium exchange caused by a decreased inward directed sodium gradient, the mechanism by which ouabain enhances the secretory response is likely to involve an increased binding of calcium to membrane binding sites."} {"id": "PMID:1279654", "title": "Involvement of opioid mechanisms in peripheral motor control of detrusor muscle.", "content": "Isometric recordings of mechanical activity in muscle strips from rat and human detrusor were performed and the effect of mu- and delta-opioid receptor stimulation and blockade on detrusor contraction induced by electrical field stimulation was tested. Stimulation of the opioid mu-receptor with morphine (10(-13)-10(-4) M) and DAGO (10(-13)-10(-6) M) had no significant effect on electrical field stimulation except at one concentration of morphine (10(-6) M). Naloxone (10(-10)-10(-5) M) caused a significant facilitation of the electrical field stimulation-induced contraction, which was counteracted by morphine (10(-8) M) and the delta-agonist DPDPE (10(-8) M) in both rat and human detrusor. Addition of atropine (10(-6) M) or hexamethonium chloride (10(-6) M) or spantide (10(-6) M) did not alter the facilitating effect of naloxone in the rat detrusor. Hexamethonium (10(-5) M) decreased the facilitating effect of naloxone on electrical field stimulation-induced contractions in the human detrusor, indicating involvement of ganglionic mechanisms. In human detrusor about 15% of the contractile response was found to be atropine-resistant (10(-6) M) and one third of this was found to be resistant to tetrodotoxin (1.5 x 10(-6) M). The atropine resistant-response in human detrusor was facilitated by naloxone to the same extent as the atropine-sensitive part. Adrenergic blockade per se, achieved with phentolamine mesylate (10(-6) M) and propranolol (10(-6) M), caused a significant facilitation of the electrical field stimulation-induced contraction in the rat detrusor but did not affect the facilitating effect of naloxone (10(-13)-10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Involvement of opioid mechanisms in peripheral motor control of detrusor muscle. Isometric recordings of mechanical activity in muscle strips from rat and human detrusor were performed and the effect of mu- and delta-opioid receptor stimulation and blockade on detrusor contraction induced by electrical field stimulation was tested. Stimulation of the opioid mu-receptor with morphine (10(-13)-10(-4) M) and DAGO (10(-13)-10(-6) M) had no significant effect on electrical field stimulation except at one concentration of morphine (10(-6) M). Naloxone (10(-10)-10(-5) M) caused a significant facilitation of the electrical field stimulation-induced contraction, which was counteracted by morphine (10(-8) M) and the delta-agonist DPDPE (10(-8) M) in both rat and human detrusor. Addition of atropine (10(-6) M) or hexamethonium chloride (10(-6) M) or spantide (10(-6) M) did not alter the facilitating effect of naloxone in the rat detrusor. Hexamethonium (10(-5) M) decreased the facilitating effect of naloxone on electrical field stimulation-induced contractions in the human detrusor, indicating involvement of ganglionic mechanisms. In human detrusor about 15% of the contractile response was found to be atropine-resistant (10(-6) M) and one third of this was found to be resistant to tetrodotoxin (1.5 x 10(-6) M). The atropine resistant-response in human detrusor was facilitated by naloxone to the same extent as the atropine-sensitive part. Adrenergic blockade per se, achieved with phentolamine mesylate (10(-6) M) and propranolol (10(-6) M), caused a significant facilitation of the electrical field stimulation-induced contraction in the rat detrusor but did not affect the facilitating effect of naloxone (10(-13)-10(-5) M).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279655", "title": "[\"Risk children\": the importance of biological and psychosocial risks for child development in the first two years of life].", "content": "In a prospective longitudinal study the development of N = 362 children will be followed over four time points (T1-T4) from birth to school age utilizing a comprehensive battery of instruments. Aims of the study are the description of the developmental course of children born at differing degrees of biological and psychosocial risk, the identification of early predictors of developmental disorders and their compensation, as well as the analysis of the processes and mechanisms underlying differential developmental patterns. The results of waves 1 and 2 show that early development from 3 to 24 months is quite unstable. Depending on the examined domain of development up to 3/4 of the disturbances of infancy have remitted by the later age, whereas nearly a fifth of the hitherto well children developed new disturbances. Both risks have a marked negative effect on development. While biological risks go hand in hand with impaired motor functioning, psychosocial risks adversely affect cognitive and social-emotional competence. However, the relative weight of risk factors changes during the first two years with biological risks becoming less important and psychosocial risk factors gaining influence. Single risk factors identified as being prognostically very unfavourable are very low birth weight and neonatal seizures. Of the psychosocial risks a pattern of unfavourable family characteristics such as low educational level, history of broken home or mental health problems of parents and chronic difficulties is related most strongly to poor outcome.", "contents": "[\"Risk children\": the importance of biological and psychosocial risks for child development in the first two years of life]. In a prospective longitudinal study the development of N = 362 children will be followed over four time points (T1-T4) from birth to school age utilizing a comprehensive battery of instruments. Aims of the study are the description of the developmental course of children born at differing degrees of biological and psychosocial risk, the identification of early predictors of developmental disorders and their compensation, as well as the analysis of the processes and mechanisms underlying differential developmental patterns. The results of waves 1 and 2 show that early development from 3 to 24 months is quite unstable. Depending on the examined domain of development up to 3/4 of the disturbances of infancy have remitted by the later age, whereas nearly a fifth of the hitherto well children developed new disturbances. Both risks have a marked negative effect on development. While biological risks go hand in hand with impaired motor functioning, psychosocial risks adversely affect cognitive and social-emotional competence. However, the relative weight of risk factors changes during the first two years with biological risks becoming less important and psychosocial risk factors gaining influence. Single risk factors identified as being prognostically very unfavourable are very low birth weight and neonatal seizures. Of the psychosocial risks a pattern of unfavourable family characteristics such as low educational level, history of broken home or mental health problems of parents and chronic difficulties is related most strongly to poor outcome."} {"id": "PMID:1279656", "title": "Increased maternal serum alpha-fetoprotein and human chorionic gonadotropin in compromised pregnancies other than for neural tube defects or Down syndrome.", "content": "Intrauterine fetal death occurred in four women who were 'screen-positive' in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore, we evaluated all 'screen-positive' women in whom both of these markers were greater than or equal to 2.0 multiples of the median. The cases fulfilling these criteria totalled 11, and only one of them had no complications. High concentrations of both MSAFP and MShCG in a number of these cases might have been caused by an increased placental volume, which, in turn, might have been induced by decreased perfusion of the placenta. We conclude that screening programmes wrongly determine a high risk of fetal NTD or DS if the concentrations of both these parameters are very high. Invasive diagnostic procedures should be avoided in these cases, particularly in view of the increased risk of an adverse pregnancy outcome.", "contents": "Increased maternal serum alpha-fetoprotein and human chorionic gonadotropin in compromised pregnancies other than for neural tube defects or Down syndrome. Intrauterine fetal death occurred in four women who were 'screen-positive' in a screening programme for neural tube defects (NTDs) and Down syndrome (DS). These women had very high levels of maternal serum alpha-fetoprotein (MSAFP) and maternal serum human chorionic gonadotropin (MShCG). Therefore, we evaluated all 'screen-positive' women in whom both of these markers were greater than or equal to 2.0 multiples of the median. The cases fulfilling these criteria totalled 11, and only one of them had no complications. High concentrations of both MSAFP and MShCG in a number of these cases might have been caused by an increased placental volume, which, in turn, might have been induced by decreased perfusion of the placenta. We conclude that screening programmes wrongly determine a high risk of fetal NTD or DS if the concentrations of both these parameters are very high. Invasive diagnostic procedures should be avoided in these cases, particularly in view of the increased risk of an adverse pregnancy outcome."} {"id": "PMID:1279657", "title": "Alpha-fetoprotein levels and yolk sac size in the first trimester of pregnancy.", "content": "Transvaginal ultrasound measurement of the yolk sac and transvaginal amniocentesis were carried out on 94 women prior to first-trimester termination of pregnancy. Maternal serum and fluids from the amniotic cavity and extraembryonic coelom were analysed for alpha-fetoprotein (AFP). No correlation was found between the yolk sac size and the levels of AFP in any of these sites.", "contents": "Alpha-fetoprotein levels and yolk sac size in the first trimester of pregnancy. Transvaginal ultrasound measurement of the yolk sac and transvaginal amniocentesis were carried out on 94 women prior to first-trimester termination of pregnancy. Maternal serum and fluids from the amniotic cavity and extraembryonic coelom were analysed for alpha-fetoprotein (AFP). No correlation was found between the yolk sac size and the levels of AFP in any of these sites."} {"id": "PMID:1279658", "title": "Prenatal demonstration of a cervical myelocystocele.", "content": "Myelocystocele is a rare spinal cord disorder and has not been described prenatally. We report a case in which prenatal ultrasound and magnetic resonance imaging (MRI) demonstrated a posterior cervical mass which was initially thought to be a meningocele or an atypical cystic hygroma. Surgery performed at 1 day of age showed this to be a myelocystocele. Therefore, the differential diagnosis of an extracranial cystic mass in the posterior cervical region should be expanded to include myelocystoceles.", "contents": "Prenatal demonstration of a cervical myelocystocele. Myelocystocele is a rare spinal cord disorder and has not been described prenatally. We report a case in which prenatal ultrasound and magnetic resonance imaging (MRI) demonstrated a posterior cervical mass which was initially thought to be a meningocele or an atypical cystic hygroma. Surgery performed at 1 day of age showed this to be a myelocystocele. Therefore, the differential diagnosis of an extracranial cystic mass in the posterior cervical region should be expanded to include myelocystoceles."} {"id": "PMID:1279659", "title": "Spontaneous cessation of umbilical blood flow in the acardiac fetus of a twin pregnancy.", "content": "The acardiac fetus is a rare entity found only in monozygotic multiple pregnancy. Although the acardiac fetus is non-viable, the perinatal mortality rate for the normal fetus may be as high as 50 per cent, and is usually associated with fetal heart failure and hydrops fetalis, or as the result of prematurity. In this communication, we describe a case of spontaneous cessation of blood flow to an acardiac fetus and discuss the management of this condition with special reference to optimizing the outcome for the normal fetus.", "contents": "Spontaneous cessation of umbilical blood flow in the acardiac fetus of a twin pregnancy. The acardiac fetus is a rare entity found only in monozygotic multiple pregnancy. Although the acardiac fetus is non-viable, the perinatal mortality rate for the normal fetus may be as high as 50 per cent, and is usually associated with fetal heart failure and hydrops fetalis, or as the result of prematurity. In this communication, we describe a case of spontaneous cessation of blood flow to an acardiac fetus and discuss the management of this condition with special reference to optimizing the outcome for the normal fetus."} {"id": "PMID:1279660", "title": "Amiodarone treatment in pregnancy for dilatative cardiomyopathy with ventricular malignant extrasystole and normal maternal and neonatal outcome.", "content": "Amiodarone treatment in pregnancy might be difficult to handle because of the long half-life of the drug (14-28 days up to 2 months) and because it reduces maternal and neonatal thyroid activity. Although short-term use in pregnancy has been described in cases of fetal supraventricular tachycardia, there are few reports on the chronic use of the drug. In this paper we describe our experience with amiodarone treatment in two pregnant sisters with familial dilatative cardiomyopathy and ventricular malignant extrasystole. Prolonged administration of amiodarone (400-200 mg/die) since the beginning of pregnancy did not have any adverse effects; maternal and neonatal thyroid function was normal, as was the neurological and motor development of the neonates.", "contents": "Amiodarone treatment in pregnancy for dilatative cardiomyopathy with ventricular malignant extrasystole and normal maternal and neonatal outcome. Amiodarone treatment in pregnancy might be difficult to handle because of the long half-life of the drug (14-28 days up to 2 months) and because it reduces maternal and neonatal thyroid activity. Although short-term use in pregnancy has been described in cases of fetal supraventricular tachycardia, there are few reports on the chronic use of the drug. In this paper we describe our experience with amiodarone treatment in two pregnant sisters with familial dilatative cardiomyopathy and ventricular malignant extrasystole. Prolonged administration of amiodarone (400-200 mg/die) since the beginning of pregnancy did not have any adverse effects; maternal and neonatal thyroid function was normal, as was the neurological and motor development of the neonates."} {"id": "PMID:1279661", "title": "Atelosteogenesis type II: sonographic and radiological correlation.", "content": "Atelosteogenesis type II is a lethal chondrodysplasia characterized by severe micromelia, spinal abnormalities, talipes equinovarus, and abducted thumbs and toes. We present a case diagnosed at 21 weeks of gestation in which antenatal sonographic and post-mortem radiological findings were correlated. The patient had a recurrence of this disorder in a subsequent pregnancy which was terminated at 15 weeks, supporting previous reports of an autosomal recessive inheritance pattern. The feasibility of diagnosing the following morphological features by prenatal ultrasonography is demonstrated: coronal clefts of the vertebral bodies, metaphyseal and epiphyseal abnormalities, spinal deviations such as cervical kyphosis and a horizontal sacrum, additional ossification centres in the pelvis, and preaxial deviation of the thumbs and toes. The differential diagnosis of this disorder from other skeletal dysplasias with similar features is discussed.", "contents": "Atelosteogenesis type II: sonographic and radiological correlation. Atelosteogenesis type II is a lethal chondrodysplasia characterized by severe micromelia, spinal abnormalities, talipes equinovarus, and abducted thumbs and toes. We present a case diagnosed at 21 weeks of gestation in which antenatal sonographic and post-mortem radiological findings were correlated. The patient had a recurrence of this disorder in a subsequent pregnancy which was terminated at 15 weeks, supporting previous reports of an autosomal recessive inheritance pattern. The feasibility of diagnosing the following morphological features by prenatal ultrasonography is demonstrated: coronal clefts of the vertebral bodies, metaphyseal and epiphyseal abnormalities, spinal deviations such as cervical kyphosis and a horizontal sacrum, additional ossification centres in the pelvis, and preaxial deviation of the thumbs and toes. The differential diagnosis of this disorder from other skeletal dysplasias with similar features is discussed."} {"id": "PMID:1279662", "title": "Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia: the diagnostic role of prenatal ultrasonography.", "content": "Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is a rare congenital disease in which localized or widespread areas of skin are absent at birth. Alphafetoprotein (AFP) and skin biopsy have been used for prenatal diagnosis of this condition. A patient in whom normal levels of amniotic AFP at 16 weeks' gestation presumably excluded the disease and who was at risk for aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is described. However, 10 weeks later, ultrasonographic examination revealed hydramnios, a dilated stomach, a deformed external ear, and a contracted fisted hand. All signs were confirmed postnatally. The role of ultrasonography and the value of other diagnostic methods in this congenital disease are discussed.", "contents": "Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia: the diagnostic role of prenatal ultrasonography. Aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is a rare congenital disease in which localized or widespread areas of skin are absent at birth. Alphafetoprotein (AFP) and skin biopsy have been used for prenatal diagnosis of this condition. A patient in whom normal levels of amniotic AFP at 16 weeks' gestation presumably excluded the disease and who was at risk for aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia is described. However, 10 weeks later, ultrasonographic examination revealed hydramnios, a dilated stomach, a deformed external ear, and a contracted fisted hand. All signs were confirmed postnatally. The role of ultrasonography and the value of other diagnostic methods in this congenital disease are discussed."} {"id": "PMID:1279663", "title": "Healthy lifestyles are associated with higher natural killer cell activity.", "content": "To investigate the association of individual lifestyle with immune response against tumors, we assayed peripheral blood lymphocytes of 62 healthy males ranging in age from 30 to 60 years for natural killer (NK) cell activity, which is the first line of defense against tumors, and for frequencies of NK cell subsets. The NK cell activity was determined by 51Cr release assay, and NK cell subsets were counted using surface antigens (CD16, CD57) which recognize NK cell subgroups with different cytolytic potentials. Subjects were classified into groups reporting good, moderate, and poor lifestyles according to their responses on a questionnaire regarding eight health practices (tobacco smoking, alcohol consumption, hours of sleep, physical exercise, eating breakfast, balanced nutrition, hours of work habits, and mental stress). Individuals reporting good lifestyle habits were found to have the highest NK cell activity and it was significantly higher than the NK cell activity in those reporting poor lifestyle habits. Those reporting good health practices regarding smoking and physical exercise showed significantly higher NK cell activity at an effector-to-target-cell ratio of 40:1. The higher NK cell activity among individuals reporting good lifestyle practices may reflect an increase in the cytolytic potential of NK cell activity within the CD16+, CD57- subset.", "contents": "Healthy lifestyles are associated with higher natural killer cell activity. To investigate the association of individual lifestyle with immune response against tumors, we assayed peripheral blood lymphocytes of 62 healthy males ranging in age from 30 to 60 years for natural killer (NK) cell activity, which is the first line of defense against tumors, and for frequencies of NK cell subsets. The NK cell activity was determined by 51Cr release assay, and NK cell subsets were counted using surface antigens (CD16, CD57) which recognize NK cell subgroups with different cytolytic potentials. Subjects were classified into groups reporting good, moderate, and poor lifestyles according to their responses on a questionnaire regarding eight health practices (tobacco smoking, alcohol consumption, hours of sleep, physical exercise, eating breakfast, balanced nutrition, hours of work habits, and mental stress). Individuals reporting good lifestyle habits were found to have the highest NK cell activity and it was significantly higher than the NK cell activity in those reporting poor lifestyle habits. Those reporting good health practices regarding smoking and physical exercise showed significantly higher NK cell activity at an effector-to-target-cell ratio of 40:1. The higher NK cell activity among individuals reporting good lifestyle practices may reflect an increase in the cytolytic potential of NK cell activity within the CD16+, CD57- subset."} {"id": "PMID:1279664", "title": "[Stent implantation in post-stenotic retention pneumonia caused by inoperable bronchial carcinoma].", "content": "The 65 year old patient referred to in this report has been suffering from an inoperable squamous cell carcinoma of the right superior lobe of the lung for the last two years. After therapeutic irradiation the disease subsided temporarily. Subsequently the patient became severely ill and was referred to hospital with high fever and refractory pneumonia. X-ray film revealed atelectasis of the right superior and central lobes and a pneumonic infiltration of the right inferior lobe. Bronchoscopy showed complete tumour stenoses of the superior and central lobes. The lower lobe of the lung was visualised as subtotally stenosed and obstructed by pus. Despite pathogen-directed antibiosis the poststenotic retention pneumonia did not heal. After laser recanalisation of the right inferior lobe we implanted an endobronchial stent. Subsequently, the pneumonia receded and the patient survived for five months relatively free from complaints.", "contents": "[Stent implantation in post-stenotic retention pneumonia caused by inoperable bronchial carcinoma]. The 65 year old patient referred to in this report has been suffering from an inoperable squamous cell carcinoma of the right superior lobe of the lung for the last two years. After therapeutic irradiation the disease subsided temporarily. Subsequently the patient became severely ill and was referred to hospital with high fever and refractory pneumonia. X-ray film revealed atelectasis of the right superior and central lobes and a pneumonic infiltration of the right inferior lobe. Bronchoscopy showed complete tumour stenoses of the superior and central lobes. The lower lobe of the lung was visualised as subtotally stenosed and obstructed by pus. Despite pathogen-directed antibiosis the poststenotic retention pneumonia did not heal. After laser recanalisation of the right inferior lobe we implanted an endobronchial stent. Subsequently, the pneumonia receded and the patient survived for five months relatively free from complaints."} {"id": "PMID:1279665", "title": "Beta-sheet folding of fragment (16-36) of bovine pancreatic trypsin inhibitor as predicted by Monte Carlo simulated annealing.", "content": "A tertiary structure prediction is described using Monte Carlo simulated annealing for the peptide fragment corresponding to residues 16-36 of bovine pancreatic trypsin inhibitor (BPTI). The simulation starts with randomly chosen initial conformations and is performed without imposing experimental constraints using energy functions given for generic interatomic interactions. Out of 20 simulation trials, seven conformations show a sheet-like structure--two strands connected by a turn--although this sheet-like structure is not as rigid as that observed in native BPTI. It is also shown that these conformations are mostly looped and exhibit a native-like right-handed twist. Unlike the case with the C-peptide of RNase A, no conspicuous alpha-helical structure is found in any of the final conformations obtained in the simulation. However, the lowest-energy conformation does not resemble exactly the native structure. This indicates that the rigid beta-sheet conformation of native BPTI merely corresponds to a local minimum of the energy function if the fragment with residues 16-36 is isolated from the native protein. A statistical analysis of all 20 final conformations suggests that the tendency for the peptide segments to form extended beta-strands is strong for those with residues 18-24, and moderate for those with residues 30-35. The segment of residues 25-29 does not tend to form any definite structure. In native BPTI, the former segments are involved in the beta-sheet and the latter in the turn. A folding scenario is also speculated from this analysis.", "contents": "Beta-sheet folding of fragment (16-36) of bovine pancreatic trypsin inhibitor as predicted by Monte Carlo simulated annealing. A tertiary structure prediction is described using Monte Carlo simulated annealing for the peptide fragment corresponding to residues 16-36 of bovine pancreatic trypsin inhibitor (BPTI). The simulation starts with randomly chosen initial conformations and is performed without imposing experimental constraints using energy functions given for generic interatomic interactions. Out of 20 simulation trials, seven conformations show a sheet-like structure--two strands connected by a turn--although this sheet-like structure is not as rigid as that observed in native BPTI. It is also shown that these conformations are mostly looped and exhibit a native-like right-handed twist. Unlike the case with the C-peptide of RNase A, no conspicuous alpha-helical structure is found in any of the final conformations obtained in the simulation. However, the lowest-energy conformation does not resemble exactly the native structure. This indicates that the rigid beta-sheet conformation of native BPTI merely corresponds to a local minimum of the energy function if the fragment with residues 16-36 is isolated from the native protein. A statistical analysis of all 20 final conformations suggests that the tendency for the peptide segments to form extended beta-strands is strong for those with residues 18-24, and moderate for those with residues 30-35. The segment of residues 25-29 does not tend to form any definite structure. In native BPTI, the former segments are involved in the beta-sheet and the latter in the turn. A folding scenario is also speculated from this analysis."} {"id": "PMID:1279666", "title": "Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease.", "content": "Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively.", "contents": "Diagnosis of hepatitis C virus (HCV) infection using an immunodominant chimeric polyprotein to capture circulating antibodies: reevaluation of the role of HCV in liver disease. Structural and nonstructural regions of the HCV-encoded polyprotein have been expressed in recombinant yeast, bacteria, or insect cells and used to capture and measure reactive antibodies circulating in different individuals. The putative nucleocapsid protein (C) and nonstructural proteins 3-5 (NS3-NS5) were found to contain the most immunodominant epitopes. The NS3, NS4, and C regions were expressed in yeast in the form of a fused, chimeric polyprotein (C25) and a capture assay for reactive antibody was developed. This anti-C25 assay detects all previously identified HCV-seropositive cases and provides a substantially more sensitive diagnostic for both acute and chronic HCV infections than the current anti-C100-3 (NS4) assay. Anti-C25 was detected more frequently than anti-C100-3 in chronic, transfusion-associated non-A, non-B hepatitis patients from the United States (95% vs. 71%) and Japan (98% vs. 82%), in cryptogenic cirrhosis patients from the United States (62% vs. 28%), and in hepatitis B surface antigen-negative cases of hepatocellular carcinoma from Japan (83% vs. 63%). These data indicate that HCV has a greater role in these liver diseases than was previously thought. In volunteer United States blood donors sampled following the introduction of anti-C100-3 screening, the prevalence of anti-C25 and anti-C100-3 was 0.5% and 0.08%, respectively."} {"id": "PMID:1279667", "title": "Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas.", "content": "Tumor necrosis factor beta (TNF-beta) (lymphotoxin) may play an important role in the immune response and pathologic inflammatory diseases. Insulitis is an important early step in the development of insulin-dependent diabetes mellitus. To understand better the role of TNF-beta in the regulation of inflammation and type 1 diabetes, we produced transgenic mice in which the murine TNF-beta gene was regulated by the rat insulin II promoter. The transgene was expressed in the pancreas, kidney, and skin of transgenic mice. The expression of TNF-beta in the pancreas of transgenic mice resulted in a leukocytic inflammatory infiltrate consisting primarily of B220+ IgM+ B cells and CD4+ and CD8+ T cells. The insulitis is reminiscent of the early stages of diabetes, though the mice did not progress to diabetes.", "contents": "Insulitis in transgenic mice expressing tumor necrosis factor beta (lymphotoxin) in the pancreas. Tumor necrosis factor beta (TNF-beta) (lymphotoxin) may play an important role in the immune response and pathologic inflammatory diseases. Insulitis is an important early step in the development of insulin-dependent diabetes mellitus. To understand better the role of TNF-beta in the regulation of inflammation and type 1 diabetes, we produced transgenic mice in which the murine TNF-beta gene was regulated by the rat insulin II promoter. The transgene was expressed in the pancreas, kidney, and skin of transgenic mice. The expression of TNF-beta in the pancreas of transgenic mice resulted in a leukocytic inflammatory infiltrate consisting primarily of B220+ IgM+ B cells and CD4+ and CD8+ T cells. The insulitis is reminiscent of the early stages of diabetes, though the mice did not progress to diabetes."} {"id": "PMID:1279668", "title": "Antisense c-myc effects on preimplantation mouse embryo development.", "content": "Antisense DNA inhibition of gene expression was explored as an approach toward elucidating mechanisms regulating development of preimplantation mammalian embryos. Specifically, a role for the c-myc protooncogene was examined. Detection of c-myc mRNA and immunoreactive nuclear c-myc protein in preimplantation mouse embryos at the eight-cell/morula and blastocyst stages suggested that this DNA-binding protein could be important during early embryo-genesis. The effects of c-myc oligodeoxyribonucleotides (oligos) on the in vitro development of two-cell mouse embryos were examined. Embryos cultured in medium containing an unmodified (phosphodiester) antisense c-myc oligo complementary to the translation initiation codon and spanning the first seven codons exhibited a dose-dependent arrest at the eight-cell/morula stage. At lower concentrations (7.5 microM) this inhibitory effect was specific to the antisense oligo and did not occur with the sense-strand complement or with duplexes of the antisense and sense oligos. However, at 4-fold higher concentrations of DNA (30 microM), all unmodified c-myc oligos were embryotoxic, causing embryos to arrest at the two-cell to four-cell stages. In contrast, almost all (98%) two-cell embryos cultured with a modified (chimeric phosphorothioate/phosphodiester) antisense c-myc oligo (7.5 microM) exhibited developmental arrest at the eight-cell/morula stage, whereas no developmental arrest occurred following incubation with high concentrations of the modified sense complement (30 microM). Culture of freshly recovered eight-cell embryos with antisense c-myc led to the absence of c-myc protein but no change in epidermal growth factor receptor in those embryos that developed a blastocoel. These effects on c-myc were specific for the antisense oligo. These results suggest that c-myc function becomes particularly critical for preimplantation mouse embryos at the eight-cell/morula stage of development and establish that antisense DNA can be successfully applied as an approach toward elucidating the roles of specific genes in preimplantation mammalian embryo development.", "contents": "Antisense c-myc effects on preimplantation mouse embryo development. Antisense DNA inhibition of gene expression was explored as an approach toward elucidating mechanisms regulating development of preimplantation mammalian embryos. Specifically, a role for the c-myc protooncogene was examined. Detection of c-myc mRNA and immunoreactive nuclear c-myc protein in preimplantation mouse embryos at the eight-cell/morula and blastocyst stages suggested that this DNA-binding protein could be important during early embryo-genesis. The effects of c-myc oligodeoxyribonucleotides (oligos) on the in vitro development of two-cell mouse embryos were examined. Embryos cultured in medium containing an unmodified (phosphodiester) antisense c-myc oligo complementary to the translation initiation codon and spanning the first seven codons exhibited a dose-dependent arrest at the eight-cell/morula stage. At lower concentrations (7.5 microM) this inhibitory effect was specific to the antisense oligo and did not occur with the sense-strand complement or with duplexes of the antisense and sense oligos. However, at 4-fold higher concentrations of DNA (30 microM), all unmodified c-myc oligos were embryotoxic, causing embryos to arrest at the two-cell to four-cell stages. In contrast, almost all (98%) two-cell embryos cultured with a modified (chimeric phosphorothioate/phosphodiester) antisense c-myc oligo (7.5 microM) exhibited developmental arrest at the eight-cell/morula stage, whereas no developmental arrest occurred following incubation with high concentrations of the modified sense complement (30 microM). Culture of freshly recovered eight-cell embryos with antisense c-myc led to the absence of c-myc protein but no change in epidermal growth factor receptor in those embryos that developed a blastocoel. These effects on c-myc were specific for the antisense oligo. These results suggest that c-myc function becomes particularly critical for preimplantation mouse embryos at the eight-cell/morula stage of development and establish that antisense DNA can be successfully applied as an approach toward elucidating the roles of specific genes in preimplantation mammalian embryo development."} {"id": "PMID:1279669", "title": "The dorsal premammillary nucleus: an unusual component of the mammillary body.", "content": "The results of anterograde and retrograde axonal transport experiments in the rat indicate that the dorsal premammillary nucleus (PMd) gives rise to a branched pathway ending in the anterior thalamic group and brainstem, like the medial and lateral mammillary nuclei. However, unlike these nuclei, the ascending PMd projection courses through and to the anterior hypothalamic nucleus, and the descending PMd projection ends in the periaqueductal gray, superior colliculus, and adjacent parts of the reticular formation. Also unlike the traditional mammillary nuclei, the PMd does not receive a direct input from the columns of the fornix; instead, it receives a bilateral input from the anterior hypothalamic nucleus, which in turn receives inputs from areas related to the prefrontal cortex, amygdala, and hippocampus. The results provide interesting perspectives on the organization of medial hypothalamic circuits underlying the goal-oriented behaviors associated with hunger, thirst, and reproduction.", "contents": "The dorsal premammillary nucleus: an unusual component of the mammillary body. The results of anterograde and retrograde axonal transport experiments in the rat indicate that the dorsal premammillary nucleus (PMd) gives rise to a branched pathway ending in the anterior thalamic group and brainstem, like the medial and lateral mammillary nuclei. However, unlike these nuclei, the ascending PMd projection courses through and to the anterior hypothalamic nucleus, and the descending PMd projection ends in the periaqueductal gray, superior colliculus, and adjacent parts of the reticular formation. Also unlike the traditional mammillary nuclei, the PMd does not receive a direct input from the columns of the fornix; instead, it receives a bilateral input from the anterior hypothalamic nucleus, which in turn receives inputs from areas related to the prefrontal cortex, amygdala, and hippocampus. The results provide interesting perspectives on the organization of medial hypothalamic circuits underlying the goal-oriented behaviors associated with hunger, thirst, and reproduction."} {"id": "PMID:1279670", "title": "Selective blockers of voltage-gated K+ channels depolarize human T lymphocytes: mechanism of the antiproliferative effect of charybdotoxin.", "content": "Charybdotoxin (ChTX), a K+ channel blocker, depolarizes human peripheral T lymphocytes and renders them insensitive to activation by mitogen. We observed four types of K+ channels in human T cells: one voltage-activated, and three Ca(2+)-activated. To discern the mechanism by which ChTX depolarizes T cells, we examined the sensitivity of both the voltage-activated and Ca(2+)-activated K+ channels to ChTX and other peptide channel blockers. All four types were blocked by ChTX, whereas noxiustoxin and margatoxin blocked only the voltage-activated channels. All three toxins, however, produced equivalent depolarization in human T cells. We conclude that the membrane potential of resting T cells is set by voltage-activated channels and that blockade of these channels is sufficient to depolarize resting human T cells and prevent activation.", "contents": "Selective blockers of voltage-gated K+ channels depolarize human T lymphocytes: mechanism of the antiproliferative effect of charybdotoxin. Charybdotoxin (ChTX), a K+ channel blocker, depolarizes human peripheral T lymphocytes and renders them insensitive to activation by mitogen. We observed four types of K+ channels in human T cells: one voltage-activated, and three Ca(2+)-activated. To discern the mechanism by which ChTX depolarizes T cells, we examined the sensitivity of both the voltage-activated and Ca(2+)-activated K+ channels to ChTX and other peptide channel blockers. All four types were blocked by ChTX, whereas noxiustoxin and margatoxin blocked only the voltage-activated channels. All three toxins, however, produced equivalent depolarization in human T cells. We conclude that the membrane potential of resting T cells is set by voltage-activated channels and that blockade of these channels is sufficient to depolarize resting human T cells and prevent activation."} {"id": "PMID:1279671", "title": "Identification of a previously unknown human collagen chain, alpha 1(XV), characterized by extensive interruptions in the triple-helical region.", "content": "A previously unknown collagen cDNA clone, PF19, was isolated from a human placenta library. The 2.1-kilobase insert has a complete open reading frame of 709 amino acids that includes 12 amino acids of the NH2-terminal domain, a principally collagenous region of 577 residues, and 120 residues of the noncollagenous COOH terminus. The collagenous part of the sequence encoded by PF19 is characterized by 13 interruptions ranging in size from 2 to 45 amino acids. Within four interruptions are consensus sequences for attachment of serine-linked glycosaminoglycans and asparagine-linked oligosaccharides suggesting that this collagen may be extensively glycosylated. A synthetic decapeptide representing a sequence at the beginning of the COOH-terminal noncollagenous domain was used to prepare an antibody in rabbits. This antiserum detected a 125-kDa bacterial collagenase-sensitive protein in Western blots of HeLa cell lysate. Consistent with the size of the collagen chain, Northern blot hybridization revealed a major transcript of 5.3 kilobases and two minor ones of 4.7 and 4.4 kilobases that are present in cultured human fibroblasts but absent from umbilical vein endothelial cells. We propose that the previously unidentified polypeptide described in this report be designated the alpha 1 chain of type XV collagen.", "contents": "Identification of a previously unknown human collagen chain, alpha 1(XV), characterized by extensive interruptions in the triple-helical region. A previously unknown collagen cDNA clone, PF19, was isolated from a human placenta library. The 2.1-kilobase insert has a complete open reading frame of 709 amino acids that includes 12 amino acids of the NH2-terminal domain, a principally collagenous region of 577 residues, and 120 residues of the noncollagenous COOH terminus. The collagenous part of the sequence encoded by PF19 is characterized by 13 interruptions ranging in size from 2 to 45 amino acids. Within four interruptions are consensus sequences for attachment of serine-linked glycosaminoglycans and asparagine-linked oligosaccharides suggesting that this collagen may be extensively glycosylated. A synthetic decapeptide representing a sequence at the beginning of the COOH-terminal noncollagenous domain was used to prepare an antibody in rabbits. This antiserum detected a 125-kDa bacterial collagenase-sensitive protein in Western blots of HeLa cell lysate. Consistent with the size of the collagen chain, Northern blot hybridization revealed a major transcript of 5.3 kilobases and two minor ones of 4.7 and 4.4 kilobases that are present in cultured human fibroblasts but absent from umbilical vein endothelial cells. We propose that the previously unidentified polypeptide described in this report be designated the alpha 1 chain of type XV collagen."} {"id": "PMID:1279672", "title": "Human monoclonal Fab fragments derived from a combinatorial library bind to respiratory syncytial virus F glycoprotein and neutralize infectivity.", "content": "Respiratory syncytial virus (RSV) is the most important cause, throughout the world, of severe viral lower respiratory tract illness in young children. Antibodies are known to mediate resistance to RSV infection and illness. We have isolated a number of human monoclonal Fab fragments to RSV F glycoprotein from a combinatorial antibody library expressed on the surface of phage. One of these neutralized a wide range of virus isolates, 10 subgroup A and 9 subgroup B isolates, with a titer (60% neutralization) of approximately 0.1-1.0 micrograms/ml. Another Fab neutralized diverse isolates at a concentration somewhat higher. These human Fab fragments show great promise for use in the prophylaxis or therapy of serious RSV lower respiratory tract disease. For intramuscular or intravenous administration, whole antibodies will be required, whereas for aerosol application, F(ab')2 or Fab fragments may suffice.", "contents": "Human monoclonal Fab fragments derived from a combinatorial library bind to respiratory syncytial virus F glycoprotein and neutralize infectivity. Respiratory syncytial virus (RSV) is the most important cause, throughout the world, of severe viral lower respiratory tract illness in young children. Antibodies are known to mediate resistance to RSV infection and illness. We have isolated a number of human monoclonal Fab fragments to RSV F glycoprotein from a combinatorial antibody library expressed on the surface of phage. One of these neutralized a wide range of virus isolates, 10 subgroup A and 9 subgroup B isolates, with a titer (60% neutralization) of approximately 0.1-1.0 micrograms/ml. Another Fab neutralized diverse isolates at a concentration somewhat higher. These human Fab fragments show great promise for use in the prophylaxis or therapy of serious RSV lower respiratory tract disease. For intramuscular or intravenous administration, whole antibodies will be required, whereas for aerosol application, F(ab')2 or Fab fragments may suffice."} {"id": "PMID:1279673", "title": "Mouse cortical collecting duct cells show nonselective cation channel activity and express a gene related to the cGMP-gated rod photoreceptor channel.", "content": "Apical nonselective cation channels with an average single-channel conductance of 34 +/- 2.3 pS were found in M-1 mouse cortical collecting duct cells. Channel activity is increased by depolarization and abolished by cytoplasmic calcium removal. Cytoplasmic application of 0.1 mM cGMP decreases channel open probability by 27%. cDNAs corresponding to approximately 40% of the coding region of the photoreceptor channel were isolated by the polymerase chain reaction from M-1 cells and a rat kidney cDNA library. The rat kidney-derived sequence differs by a single base, and the M-1-cell-derived sequence differs by only two bases, from the photoreceptor sequence. A second clone from M-1 cells differs by 20 out of 426 bases from the photoreceptor sequence. In all three clones, the deduced amino acid sequence is identical to that of the rat photoreceptor channel. Northern blot analysis of poly(A)+ RNA from M-1 cells reveals the presence of a 3.2-kilobase band hybridizing with a retinal cGMP-gated cation channel probe. The results suggest the expression in M-1 cells of more than one gene coding for nonselective cation channels or channel subunits, one of which is identical to the cGMP-gated cation channel gene of rod photoreceptors.", "contents": "Mouse cortical collecting duct cells show nonselective cation channel activity and express a gene related to the cGMP-gated rod photoreceptor channel. Apical nonselective cation channels with an average single-channel conductance of 34 +/- 2.3 pS were found in M-1 mouse cortical collecting duct cells. Channel activity is increased by depolarization and abolished by cytoplasmic calcium removal. Cytoplasmic application of 0.1 mM cGMP decreases channel open probability by 27%. cDNAs corresponding to approximately 40% of the coding region of the photoreceptor channel were isolated by the polymerase chain reaction from M-1 cells and a rat kidney cDNA library. The rat kidney-derived sequence differs by a single base, and the M-1-cell-derived sequence differs by only two bases, from the photoreceptor sequence. A second clone from M-1 cells differs by 20 out of 426 bases from the photoreceptor sequence. In all three clones, the deduced amino acid sequence is identical to that of the rat photoreceptor channel. Northern blot analysis of poly(A)+ RNA from M-1 cells reveals the presence of a 3.2-kilobase band hybridizing with a retinal cGMP-gated cation channel probe. The results suggest the expression in M-1 cells of more than one gene coding for nonselective cation channels or channel subunits, one of which is identical to the cGMP-gated cation channel gene of rod photoreceptors."} {"id": "PMID:1279674", "title": "Molecular cloning of a somatostatin-28 receptor and comparison of its expression pattern with that of a somatostatin-14 receptor in rat brain.", "content": "The tetradecapeptide somatotropin-release inhibiting factor somatostatin-14 regulates the release of peptide hormones and also functions as neurotransmitter. The octacosapeptide somatostatin-28, the N-terminally extended form of somatostatin-14, shows similar biological activities yet with different potencies. Both peptides most likely function through distinct receptors. Here we report on the molecular and functional characterization of a somatostatin-28 receptor (SSR-28) cloned from a rat brain cDNA library. The nucleotide sequence contains an open reading frame for a protein of 428 amino acid residues with a predicted molecular mass of 47 kDa. Binding assays using radiolabeled somatostatin-14 and membranes from COS cells transfected with the cloned cDNA show that this receptor, SSR-28, has a higher binding affinity for somatostatin-28 (IC50 = 0.24 nM) than for somatostatin-14 (IC50 = 0.89 nM). RNA blot analysis reveals a 4.4-kilobase mRNA in rat cerebellum and at significantly lower abundance in other brain regions. In situ hybridization indicates that SSR-28 mRNA is present in the granular and Purkinje cell layers of the cerebellum and in the large cells of the hypoglossal nucleus of the brain stem. Signals for SSR-28 mRNA do not overlap with those of a previously cloned rat receptor that preferentially binds somatostatin-14 (SSR-14). SSR-14 mRNA is found in the medial cerebellar nucleus, horizontal limb of the diagonal band, various hypothalamic nuclei, and in layers IV and V of the cortex. In the rat cerebellum, SSR-14 and SSR-28 mRNAs are developmentally regulated; the levels of the former are highest around birth and levels of the latter are highest at the adult stage.", "contents": "Molecular cloning of a somatostatin-28 receptor and comparison of its expression pattern with that of a somatostatin-14 receptor in rat brain. The tetradecapeptide somatotropin-release inhibiting factor somatostatin-14 regulates the release of peptide hormones and also functions as neurotransmitter. The octacosapeptide somatostatin-28, the N-terminally extended form of somatostatin-14, shows similar biological activities yet with different potencies. Both peptides most likely function through distinct receptors. Here we report on the molecular and functional characterization of a somatostatin-28 receptor (SSR-28) cloned from a rat brain cDNA library. The nucleotide sequence contains an open reading frame for a protein of 428 amino acid residues with a predicted molecular mass of 47 kDa. Binding assays using radiolabeled somatostatin-14 and membranes from COS cells transfected with the cloned cDNA show that this receptor, SSR-28, has a higher binding affinity for somatostatin-28 (IC50 = 0.24 nM) than for somatostatin-14 (IC50 = 0.89 nM). RNA blot analysis reveals a 4.4-kilobase mRNA in rat cerebellum and at significantly lower abundance in other brain regions. In situ hybridization indicates that SSR-28 mRNA is present in the granular and Purkinje cell layers of the cerebellum and in the large cells of the hypoglossal nucleus of the brain stem. Signals for SSR-28 mRNA do not overlap with those of a previously cloned rat receptor that preferentially binds somatostatin-14 (SSR-14). SSR-14 mRNA is found in the medial cerebellar nucleus, horizontal limb of the diagonal band, various hypothalamic nuclei, and in layers IV and V of the cortex. In the rat cerebellum, SSR-14 and SSR-28 mRNAs are developmentally regulated; the levels of the former are highest around birth and levels of the latter are highest at the adult stage."} {"id": "PMID:1279675", "title": "Activation of human peripheral blood T lymphocytes by pharmacological induction of protein-tyrosine phosphorylation.", "content": "Protein-tyrosine kinase and protein-tyrosine phosphatase (PTPase) activities are essential for T-cell antigen receptor-mediated signaling. To assess the functional consequences of alteration of the levels of tyrosine phosphorylation in normal human T cells, the effects of vanadate and hydrogen peroxide were studied. In combination, these agents induced tyrosine phosphorylation of cellular substrates, elevated cytosolic free calcium, and induced interleukin 2 receptor (IL-2R) alpha chain expression but not IL-2 secretion. However, anti-CD28 antibody in combination with vanadate and hydrogen peroxide induced IL-2 secretion, consistent with the requirement for a costimulatory signal in the induction of this gene. The effects of vanadate and hydrogen peroxide were enhanced in the absence of the T-cell PTPase, CD45. Thus, acute pharmacologic manipulation of the level of tyrosine phosphorylation in normal T cells correlates with partial, but not full, activation of these cells; in concert with a costimulatory signal provided by perturbation of the CD28 molecule, the complete program of activation is initiated. These agents should prove useful in dissecting signaling pathways involved in the regulation of genes critical to the immune response.", "contents": "Activation of human peripheral blood T lymphocytes by pharmacological induction of protein-tyrosine phosphorylation. Protein-tyrosine kinase and protein-tyrosine phosphatase (PTPase) activities are essential for T-cell antigen receptor-mediated signaling. To assess the functional consequences of alteration of the levels of tyrosine phosphorylation in normal human T cells, the effects of vanadate and hydrogen peroxide were studied. In combination, these agents induced tyrosine phosphorylation of cellular substrates, elevated cytosolic free calcium, and induced interleukin 2 receptor (IL-2R) alpha chain expression but not IL-2 secretion. However, anti-CD28 antibody in combination with vanadate and hydrogen peroxide induced IL-2 secretion, consistent with the requirement for a costimulatory signal in the induction of this gene. The effects of vanadate and hydrogen peroxide were enhanced in the absence of the T-cell PTPase, CD45. Thus, acute pharmacologic manipulation of the level of tyrosine phosphorylation in normal T cells correlates with partial, but not full, activation of these cells; in concert with a costimulatory signal provided by perturbation of the CD28 molecule, the complete program of activation is initiated. These agents should prove useful in dissecting signaling pathways involved in the regulation of genes critical to the immune response."} {"id": "PMID:1279676", "title": "T-cell activation molecule 4-1BB binds to extracellular matrix proteins.", "content": "The recently isolated 4-1BB cDNA clone encodes a cell surface protein expressed by activated T cells. Its extracellular domain is homologous to members of the nerve growth factor receptor super family and its cytoplasmic domain contains a sequence homologous to the binding site for the T-cell-specific tyrosine kinase p56lck found in the cytoplasmic domains of CD4 and CD8 alpha. At present the function of 4-1BB is not known. We prepared a 4-1BB-immunoglobulin fusion protein (4-1BB Rg). This protein was used in immunohistochemical studies to identify tissues that express the 4-1BB ligand. 4-1BB Rg bound to virtually all tissues examined, suggesting that extracellular components might function as its ligands. To explore this possibility, 4-1BB was expressed in COS cells and found to mediate the binding of fibronectin, vitronectin, laminin, and collagen VI but not of collagen I. The binding of extracellular matrix proteins to 4-1BB was not mediated by Arg-Gly-Asp (RGD) or CS-1 amino acid sequences. Experiments with overlapping proteolytic fragments of fibronectin showed that 4-1BB interacts with multiple regions of fibronectin. The interaction between extracellular matrix proteins and 4-1BB was completely blocked by the anionic carbohydrate polymer fucoidan and was partially blocked by the anionic carbohydrate polymer dextran sulfate and the glycosaminoglycan heparin sulfate but was unaffected by desulfated heparin. These results suggest that carbohydrates may play a role in mediating the 4-1BB-extracellular matrix protein adhesion.", "contents": "T-cell activation molecule 4-1BB binds to extracellular matrix proteins. The recently isolated 4-1BB cDNA clone encodes a cell surface protein expressed by activated T cells. Its extracellular domain is homologous to members of the nerve growth factor receptor super family and its cytoplasmic domain contains a sequence homologous to the binding site for the T-cell-specific tyrosine kinase p56lck found in the cytoplasmic domains of CD4 and CD8 alpha. At present the function of 4-1BB is not known. We prepared a 4-1BB-immunoglobulin fusion protein (4-1BB Rg). This protein was used in immunohistochemical studies to identify tissues that express the 4-1BB ligand. 4-1BB Rg bound to virtually all tissues examined, suggesting that extracellular components might function as its ligands. To explore this possibility, 4-1BB was expressed in COS cells and found to mediate the binding of fibronectin, vitronectin, laminin, and collagen VI but not of collagen I. The binding of extracellular matrix proteins to 4-1BB was not mediated by Arg-Gly-Asp (RGD) or CS-1 amino acid sequences. Experiments with overlapping proteolytic fragments of fibronectin showed that 4-1BB interacts with multiple regions of fibronectin. The interaction between extracellular matrix proteins and 4-1BB was completely blocked by the anionic carbohydrate polymer fucoidan and was partially blocked by the anionic carbohydrate polymer dextran sulfate and the glycosaminoglycan heparin sulfate but was unaffected by desulfated heparin. These results suggest that carbohydrates may play a role in mediating the 4-1BB-extracellular matrix protein adhesion."} {"id": "PMID:1279677", "title": "A region of group I introns that contains universally conserved residues but is not essential for self-splicing.", "content": "The catalytic core of the self-splicing group I intron RNAs is composed of six paired regions together with their connecting sequences; these are thought to form two elongated domains, with paired regions P5, P4, and P6 aligned along one axis and P8, P3, and P7 along the other. Most of the very highly conserved residues of the group I introns lie in or near P7, but two occur in L4, the internal loop connecting P4 and P5. It is generally believed that such bases are conserved because they are essential for splicing. Mutants were created in a member of each of the two major subclasses of group I introns, in which P5, L4, and the distal portion of P4 were deleted. Splicing activity was still detected in these mutants, albeit substantially weakened; splicing was accurate and occurred by the normal group I mechanism, with addition of a guanosine molecule to the intron. Thus the deleted region, containing two universally conserved bases, is not essential but facilitates splicing. Another reaction characteristic of group I introns, hydrolysis of the 3' splice site, was less severely affected by the deletions. The results are discussed in terms of the prevailing three-dimensional model for the core structure of the group I introns.", "contents": "A region of group I introns that contains universally conserved residues but is not essential for self-splicing. The catalytic core of the self-splicing group I intron RNAs is composed of six paired regions together with their connecting sequences; these are thought to form two elongated domains, with paired regions P5, P4, and P6 aligned along one axis and P8, P3, and P7 along the other. Most of the very highly conserved residues of the group I introns lie in or near P7, but two occur in L4, the internal loop connecting P4 and P5. It is generally believed that such bases are conserved because they are essential for splicing. Mutants were created in a member of each of the two major subclasses of group I introns, in which P5, L4, and the distal portion of P4 were deleted. Splicing activity was still detected in these mutants, albeit substantially weakened; splicing was accurate and occurred by the normal group I mechanism, with addition of a guanosine molecule to the intron. Thus the deleted region, containing two universally conserved bases, is not essential but facilitates splicing. Another reaction characteristic of group I introns, hydrolysis of the 3' splice site, was less severely affected by the deletions. The results are discussed in terms of the prevailing three-dimensional model for the core structure of the group I introns."} {"id": "PMID:1279678", "title": "Specificity determinants and structural features in the RNA target of the bacterial antiterminator proteins of the BglG/SacY family.", "content": "Induction of the Bacillus subtilis sacB gene and sacPA operon and Escherichia coli bgl operon is mediated by structurally homologous antiterminators encoded by the sacY, sacT, and bglG genes, respectively. When activated, these proteins prevent early transcription termination at terminators located in the leader regions of the three operons. BglG was previously shown to bind in vitro to an imperfectly palindromic 29-nucleotide RNA sequence located upstream of the terminator and partially overlapping with it [Houman, F., Diaz-Torres, M.R. & Wright, A. (1990) Cell 62, 1153-1163]. Similar motifs, here termed ribonucleic antiterminators (RATs), strongly conserved in sequence and in position, are found in the leader of both sacB and sacPA. Mutations were created in sacB RAT and tested in B. subtilis; this showed that sacB RAT is the target for SacY-mediated induction of sacB and that a stem-loop structure in the mRNA is required for regulatory function. Mutations increasing the similarity of the sacB RAT with those of sacPA or bgl rendered sacB inducible by SacT or BglG, respectively; most of these changes did not strongly affect induction by SacY, suggesting that the nucleotides at these variable positions act as negative specificity determinants.", "contents": "Specificity determinants and structural features in the RNA target of the bacterial antiterminator proteins of the BglG/SacY family. Induction of the Bacillus subtilis sacB gene and sacPA operon and Escherichia coli bgl operon is mediated by structurally homologous antiterminators encoded by the sacY, sacT, and bglG genes, respectively. When activated, these proteins prevent early transcription termination at terminators located in the leader regions of the three operons. BglG was previously shown to bind in vitro to an imperfectly palindromic 29-nucleotide RNA sequence located upstream of the terminator and partially overlapping with it [Houman, F., Diaz-Torres, M.R. & Wright, A. (1990) Cell 62, 1153-1163]. Similar motifs, here termed ribonucleic antiterminators (RATs), strongly conserved in sequence and in position, are found in the leader of both sacB and sacPA. Mutations were created in sacB RAT and tested in B. subtilis; this showed that sacB RAT is the target for SacY-mediated induction of sacB and that a stem-loop structure in the mRNA is required for regulatory function. Mutations increasing the similarity of the sacB RAT with those of sacPA or bgl rendered sacB inducible by SacT or BglG, respectively; most of these changes did not strongly affect induction by SacY, suggesting that the nucleotides at these variable positions act as negative specificity determinants."} {"id": "PMID:1279679", "title": "Cultured sympathetic neurons synthesize and release the cytokine interleukin 1 beta.", "content": "Autonomic neurons help to regulate immune responses, and there are reciprocal interactions between the nervous and immune systems. This study seeks to define some of the molecular mechanisms that may underlie such interactions. Immunoblot analysis indicated that cultured sympathetic neurons synthesize and release the cytokine interleukin 1 beta (IL-1 beta). In addition, RNA blot analysis of cultured sympathetic neurons demonstrated that the neurons contain mRNA encoding IL-1 beta. It was previously shown that explant cultures of sympathetic ganglia and dissociated cocultures of neurons with ganglionic nonneuronal cells synthesize substance P, whereas in situ levels of substance P and its mRNA are low. An antagonist at the interleukin 1 receptor markedly depressed this increase in substance P in cultures, suggesting that endogenous IL-1 beta mediates the synthetic response, at least in part. Because pure neuronal cultures do not contain substance P and neurons synthesize and release IL-1 beta, the actions of the cytokine require the presence of ganglion nonneuronal cells. These observations suggest a role for autonomic neurons in influencing immune responses by synthesizing and secreting at least two known immunoregulators, the cytokine IL-1 beta and the neuropeptide substance P.", "contents": "Cultured sympathetic neurons synthesize and release the cytokine interleukin 1 beta. Autonomic neurons help to regulate immune responses, and there are reciprocal interactions between the nervous and immune systems. This study seeks to define some of the molecular mechanisms that may underlie such interactions. Immunoblot analysis indicated that cultured sympathetic neurons synthesize and release the cytokine interleukin 1 beta (IL-1 beta). In addition, RNA blot analysis of cultured sympathetic neurons demonstrated that the neurons contain mRNA encoding IL-1 beta. It was previously shown that explant cultures of sympathetic ganglia and dissociated cocultures of neurons with ganglionic nonneuronal cells synthesize substance P, whereas in situ levels of substance P and its mRNA are low. An antagonist at the interleukin 1 receptor markedly depressed this increase in substance P in cultures, suggesting that endogenous IL-1 beta mediates the synthetic response, at least in part. Because pure neuronal cultures do not contain substance P and neurons synthesize and release IL-1 beta, the actions of the cytokine require the presence of ganglion nonneuronal cells. These observations suggest a role for autonomic neurons in influencing immune responses by synthesizing and secreting at least two known immunoregulators, the cytokine IL-1 beta and the neuropeptide substance P."} {"id": "PMID:1279680", "title": "Parental imprinting studied by allele-specific primer extension after PCR: paternal X chromosome-linked genes are transcribed prior to preferential paternal X chromosome inactivation.", "content": "The preferential inactivation of the paternal X chromosome in extraembryonic cells during early mouse development is an example of parental imprinting, but it has not been studied at the transcriptional level because standard methods of measuring RNA levels do not allow detection of allele-specific RNAs in individual early embryos. We sought to determine whether the paternal allele of the X chromosome-linked gene for 3-phosphoglycerate kinase 1 (Pgk-1), which is located very near the center of X chromosome inactivation, is transcribed prior to differentiation of extraembryonic lineages. Previous reports indicated that in heterozygous embryos there is a delay in the appearance of the phosphoglycerate kinase 1 allozyme encoded by the paternal X chromosome until 2 days after the appearance of the corresponding maternal allozyme. We report results obtained by use of a reverse transcription/PCR-based method which allows the quantitative measurement of allele-specific RNA. The assay is sensitive enough for the quantitative analysis in single embryos of allele-specific transcripts differing by only one nucleotide. We have used this assay to analyze mouse embryos heterozygous at the Pgk-1 and Hprt [hypoxanthine (guanine) phosphoribosyltransferase] loci, and we find that individual 8-cell and blastocyst embryos express both Hprt and Pgk-1 paternal transcripts, as do pooled 2- to 4-cell embryos. These results are discussed in view of the apparent temporal delay in paternal expression of the Pgk-1 gene at the enzyme level.", "contents": "Parental imprinting studied by allele-specific primer extension after PCR: paternal X chromosome-linked genes are transcribed prior to preferential paternal X chromosome inactivation. The preferential inactivation of the paternal X chromosome in extraembryonic cells during early mouse development is an example of parental imprinting, but it has not been studied at the transcriptional level because standard methods of measuring RNA levels do not allow detection of allele-specific RNAs in individual early embryos. We sought to determine whether the paternal allele of the X chromosome-linked gene for 3-phosphoglycerate kinase 1 (Pgk-1), which is located very near the center of X chromosome inactivation, is transcribed prior to differentiation of extraembryonic lineages. Previous reports indicated that in heterozygous embryos there is a delay in the appearance of the phosphoglycerate kinase 1 allozyme encoded by the paternal X chromosome until 2 days after the appearance of the corresponding maternal allozyme. We report results obtained by use of a reverse transcription/PCR-based method which allows the quantitative measurement of allele-specific RNA. The assay is sensitive enough for the quantitative analysis in single embryos of allele-specific transcripts differing by only one nucleotide. We have used this assay to analyze mouse embryos heterozygous at the Pgk-1 and Hprt [hypoxanthine (guanine) phosphoribosyltransferase] loci, and we find that individual 8-cell and blastocyst embryos express both Hprt and Pgk-1 paternal transcripts, as do pooled 2- to 4-cell embryos. These results are discussed in view of the apparent temporal delay in paternal expression of the Pgk-1 gene at the enzyme level."} {"id": "PMID:1279681", "title": "Molecular characterization and nephron distribution of a family of transcripts encoding the pore-forming subunit of Ca2+ channels in the kidney.", "content": "Active, transepithelial, Ca2+ reabsorption in kidney occurs primarily in the distal convoluted tubule. Recent evidence suggests that entry of Ca2+ at the apical membrane through channels bearing resemblance to those of the voltage-dependent L type may be the rate-determining step in Ca2+ reabsorption. To determine the molecular identity of the pore-forming subunit of voltage-dependent Ca2+ channel(s) in the kidney, a homology-based PCR cloning strategy was employed. Nondegenerate primers, based on conserved regions of the published cDNA sequences of voltage-dependent Ca2+ channel alpha 1 subunits, were used to amplify cDNA from rat kidney, and the products were subcloned and sequenced. A family of molecular species was identified, representing alternatively spliced transcripts of four known genes encoding these channel subunits. Northern blot analysis indicated that the expression of each of the genes exhibits a distinct spatial distribution within the kidney. One gene, CaCh4, is expressed primarily in the cortex, and by microdissected-tubule PCR was found predominantly in the distal convoluted tubule, consistent with a role in transepithelial Ca2+ reabsorption at this site.", "contents": "Molecular characterization and nephron distribution of a family of transcripts encoding the pore-forming subunit of Ca2+ channels in the kidney. Active, transepithelial, Ca2+ reabsorption in kidney occurs primarily in the distal convoluted tubule. Recent evidence suggests that entry of Ca2+ at the apical membrane through channels bearing resemblance to those of the voltage-dependent L type may be the rate-determining step in Ca2+ reabsorption. To determine the molecular identity of the pore-forming subunit of voltage-dependent Ca2+ channel(s) in the kidney, a homology-based PCR cloning strategy was employed. Nondegenerate primers, based on conserved regions of the published cDNA sequences of voltage-dependent Ca2+ channel alpha 1 subunits, were used to amplify cDNA from rat kidney, and the products were subcloned and sequenced. A family of molecular species was identified, representing alternatively spliced transcripts of four known genes encoding these channel subunits. Northern blot analysis indicated that the expression of each of the genes exhibits a distinct spatial distribution within the kidney. One gene, CaCh4, is expressed primarily in the cortex, and by microdissected-tubule PCR was found predominantly in the distal convoluted tubule, consistent with a role in transepithelial Ca2+ reabsorption at this site."} {"id": "PMID:1279682", "title": "TFC3: gene encoding the B-block binding subunit of the yeast transcription factor IIIC.", "content": "Yeast transcription factor IIIC (TFIIIC) is a multisubunit protein complex that interacts with two control elements of class III promoters called the A and B blocks. Here we describe the gene encoding the 138-kDa subunit (tau 138), which is involved in B-block binding. From the DNA sequence, the open reading frame, interrupted by an intron with an unusual 3' splice acceptor site, is in agreement with all the microsequencing data for peptides within tau 138. TFC3 is a single-copy gene located on chromosome I; it is essential for cell viability as shown by a gene disruption experiment. Epitope-tagging of the TFC3 gene product and DNA binding experiments are consistent with the presence of one copy of tau 138 in TFIIIC-DNA complexes.", "contents": "TFC3: gene encoding the B-block binding subunit of the yeast transcription factor IIIC. Yeast transcription factor IIIC (TFIIIC) is a multisubunit protein complex that interacts with two control elements of class III promoters called the A and B blocks. Here we describe the gene encoding the 138-kDa subunit (tau 138), which is involved in B-block binding. From the DNA sequence, the open reading frame, interrupted by an intron with an unusual 3' splice acceptor site, is in agreement with all the microsequencing data for peptides within tau 138. TFC3 is a single-copy gene located on chromosome I; it is essential for cell viability as shown by a gene disruption experiment. Epitope-tagging of the TFC3 gene product and DNA binding experiments are consistent with the presence of one copy of tau 138 in TFIIIC-DNA complexes."} {"id": "PMID:1279683", "title": "Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts.", "content": "Caveolae are flask-shaped plasma membrane invaginations abundant in endothelium and muscle but may be present in all cells. They contain a filamentous coat material thought to be important in their structure and function. Recent studies have demonstrated that a 22-kDa protein (caveolin) phosphorylated on tyrosine in Rous sarcoma virus-transformed chicken fibroblasts is a component of the caveolae coat on the inner aspect of the membrane. We now report the deduced protein sequence of chicken caveolin derived from cDNA PCR products and genomic DNA clones. Caveolin is a unique protein of 178 amino acids and displays little sequence similarity to other proteins in the GenBank data base. Hydrophobicity predictions indicate an unusual 40-amino acid hydrophobic region near the C terminus that may be used to anchor the protein to the membrane. When chicken caveolin was expressed in mouse 3T3 cells and detected by immunofluorescence microscopy, the typical caveolae pattern was observed. This includes brightly fluorescent membrane patches in many cases concentrated at the margin of cells and in arrays. Caveolae may be distinct from other membrane domains due at least in part to caveolin.", "contents": "Sequence and expression of caveolin, a protein component of caveolae plasma membrane domains phosphorylated on tyrosine in Rous sarcoma virus-transformed fibroblasts. Caveolae are flask-shaped plasma membrane invaginations abundant in endothelium and muscle but may be present in all cells. They contain a filamentous coat material thought to be important in their structure and function. Recent studies have demonstrated that a 22-kDa protein (caveolin) phosphorylated on tyrosine in Rous sarcoma virus-transformed chicken fibroblasts is a component of the caveolae coat on the inner aspect of the membrane. We now report the deduced protein sequence of chicken caveolin derived from cDNA PCR products and genomic DNA clones. Caveolin is a unique protein of 178 amino acids and displays little sequence similarity to other proteins in the GenBank data base. Hydrophobicity predictions indicate an unusual 40-amino acid hydrophobic region near the C terminus that may be used to anchor the protein to the membrane. When chicken caveolin was expressed in mouse 3T3 cells and detected by immunofluorescence microscopy, the typical caveolae pattern was observed. This includes brightly fluorescent membrane patches in many cases concentrated at the margin of cells and in arrays. Caveolae may be distinct from other membrane domains due at least in part to caveolin."} {"id": "PMID:1279684", "title": "Interleukin 4 regulates induction of sialoadhesin, the macrophage sialic acid-specific receptor.", "content": "Sialoadhesin is a nonphagocytic lectin-like receptor found on a restricted population of tissue macrophages in lymphoid and hemopoietic tissues. In bone marrow, it is localized to areas of contact between the resident stromal macrophages and developing granulocytes, which together form myeloblastic clusters. Sialoadhesin is highly specific for sialylated glycoconjugates and may play a role in adhesion and trophic hemopoietic cell interactions, although its function is unknown. Resident peritoneal macrophages do not express high levels of sialoadhesin in vitro unless an inducing element found in normal mouse serum is present. The restricted in vivo location of this marker and its induction by mouse serum prompted us to examine the possible influence of various cytokines on its expression, measured by a sheep erythrocyte rosetting assay. None of the cytokines tested was able to induce sialoadhesin; however, interleukin 4 (IL-4) prevented the induction in the presence of serum. Expression of other macrophage markers was not influenced in parallel, and Western blotting showed that sialoadhesin antigen in cell lysates was selectively reduced by IL-4. Inhibition by IL-4 was dose dependent, could be blocked by antibodies to both IL-4 and the IL-4 receptor, and was overcome by increased serum concentrations. IL-4 is therefore a potent cytokine regulator of the sialic acid-specific receptor implicated in macrophage-hemopoietic cell interactions.", "contents": "Interleukin 4 regulates induction of sialoadhesin, the macrophage sialic acid-specific receptor. Sialoadhesin is a nonphagocytic lectin-like receptor found on a restricted population of tissue macrophages in lymphoid and hemopoietic tissues. In bone marrow, it is localized to areas of contact between the resident stromal macrophages and developing granulocytes, which together form myeloblastic clusters. Sialoadhesin is highly specific for sialylated glycoconjugates and may play a role in adhesion and trophic hemopoietic cell interactions, although its function is unknown. Resident peritoneal macrophages do not express high levels of sialoadhesin in vitro unless an inducing element found in normal mouse serum is present. The restricted in vivo location of this marker and its induction by mouse serum prompted us to examine the possible influence of various cytokines on its expression, measured by a sheep erythrocyte rosetting assay. None of the cytokines tested was able to induce sialoadhesin; however, interleukin 4 (IL-4) prevented the induction in the presence of serum. Expression of other macrophage markers was not influenced in parallel, and Western blotting showed that sialoadhesin antigen in cell lysates was selectively reduced by IL-4. Inhibition by IL-4 was dose dependent, could be blocked by antibodies to both IL-4 and the IL-4 receptor, and was overcome by increased serum concentrations. IL-4 is therefore a potent cytokine regulator of the sialic acid-specific receptor implicated in macrophage-hemopoietic cell interactions."} {"id": "PMID:1279685", "title": "A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1.", "content": "Corticosteroids are the preeminent antiinflammatory agents although the molecular mechanisms that impart their efficacy have not been defined. The endothelium plays a critical role in inflammation by directing circulating leukocytes into extravascular tissues by expressing adhesive molecules for leukocytes [e.g., endothelial-leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion molecule 1 (ICAM-1)]. We therefore determined whether corticosteroids suppress inflammation by inhibiting endothelial expression of adhesion molecules for neutrophils (polymorphonuclear leukocytes). Preincubation of endothelial cells with endotoxin [lipopolysaccharide (LPS), 1 microgram/ml] led to a 4-fold increase in subsequent adherence of polymorphonuclear leukocytes (P < 0.0001, n = 10) to endothelial cells, an increase that was markedly attenuated when endothelial cells were treated with dexamethasone (IC50 < 1 nM, P < 0.0001, n = 6 or 7) during preincubation with LPS. Moreover, the steroid receptor agonist cortisol (10 microM), but not its inactive metabolite tetrahydrocortisol (10 microM), diminished LPS-induced endothelial cell adhesiveness. Further evidence that the action of dexamethasone was mediated through ligation of corticosteroid receptors [human glucocorticoid receptors (hGRs)] was provided by experiments utilizing the steroid antagonist RU-486. RU-486 (10 microM), which prevents translocation of ligated hGR to the nucleus by inhibiting dissociation of hGR from heat shock protein 90, completely aborted the effect of dexamethasone on adhesiveness of endothelial cells (P < 0.0005, n = 3). Treatment of endothelial cells with LPS (1 microgram/ml) stimulated transcription of ELAM-1, as shown by Northern blot analysis, and expression of membrane-associated ELAM-1 and ICAM-1, as shown by quantitative immunofluorescence (both P < 0.001, n = 9). Dexamethasone markedly inhibited LPS-stimulated accumulation of mRNA for ELAM-1 and expression of ELAM-1 and ICAM-1 (IC50 < 10 nM, both P < 0.001, n = 4-9); inhibition of expression by dexamethasone was reversed by RU-486 (both P < 0.005, n = 4-6). As in the adhesion studies, cortisol but not tetrahydrocortisol inhibited expression of ELAM-1 and ICAM-1 (both P < 0.005, n = 3 or 4). In contrast, sodium salicylate (1 mM) inhibited neither adhesion nor expression of these adhesion molecules. These studies suggest that antagonism by dexamethasone of endotoxin-induced inflammation is a specific instance of the general biological principle that the glucocorticoid receptor is a hormone-dependent regulator of transcription.", "contents": "A mechanism for the antiinflammatory effects of corticosteroids: the glucocorticoid receptor regulates leukocyte adhesion to endothelial cells and expression of endothelial-leukocyte adhesion molecule 1 and intercellular adhesion molecule 1. Corticosteroids are the preeminent antiinflammatory agents although the molecular mechanisms that impart their efficacy have not been defined. The endothelium plays a critical role in inflammation by directing circulating leukocytes into extravascular tissues by expressing adhesive molecules for leukocytes [e.g., endothelial-leukocyte adhesion molecule 1 (ELAM-1) and intercellular adhesion molecule 1 (ICAM-1)]. We therefore determined whether corticosteroids suppress inflammation by inhibiting endothelial expression of adhesion molecules for neutrophils (polymorphonuclear leukocytes). Preincubation of endothelial cells with endotoxin [lipopolysaccharide (LPS), 1 microgram/ml] led to a 4-fold increase in subsequent adherence of polymorphonuclear leukocytes (P < 0.0001, n = 10) to endothelial cells, an increase that was markedly attenuated when endothelial cells were treated with dexamethasone (IC50 < 1 nM, P < 0.0001, n = 6 or 7) during preincubation with LPS. Moreover, the steroid receptor agonist cortisol (10 microM), but not its inactive metabolite tetrahydrocortisol (10 microM), diminished LPS-induced endothelial cell adhesiveness. Further evidence that the action of dexamethasone was mediated through ligation of corticosteroid receptors [human glucocorticoid receptors (hGRs)] was provided by experiments utilizing the steroid antagonist RU-486. RU-486 (10 microM), which prevents translocation of ligated hGR to the nucleus by inhibiting dissociation of hGR from heat shock protein 90, completely aborted the effect of dexamethasone on adhesiveness of endothelial cells (P < 0.0005, n = 3). Treatment of endothelial cells with LPS (1 microgram/ml) stimulated transcription of ELAM-1, as shown by Northern blot analysis, and expression of membrane-associated ELAM-1 and ICAM-1, as shown by quantitative immunofluorescence (both P < 0.001, n = 9). Dexamethasone markedly inhibited LPS-stimulated accumulation of mRNA for ELAM-1 and expression of ELAM-1 and ICAM-1 (IC50 < 10 nM, both P < 0.001, n = 4-9); inhibition of expression by dexamethasone was reversed by RU-486 (both P < 0.005, n = 4-6). As in the adhesion studies, cortisol but not tetrahydrocortisol inhibited expression of ELAM-1 and ICAM-1 (both P < 0.005, n = 3 or 4). In contrast, sodium salicylate (1 mM) inhibited neither adhesion nor expression of these adhesion molecules. These studies suggest that antagonism by dexamethasone of endotoxin-induced inflammation is a specific instance of the general biological principle that the glucocorticoid receptor is a hormone-dependent regulator of transcription."} {"id": "PMID:1279686", "title": "Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland.", "content": "Diazepam-binding inhibitor (DBI) is a 9-kDa polypeptide that colocalizes in glial, adrenocortical, and Leydig cells with the mitochondrial DBI receptor (MDR). By binding with high affinity to the MDR, DBI and one of its processing products--DBI-(17-50)--regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH). In adrenals of hypophysectomized rats (1 day after surgery), ACTH failed to acutely affect the amount of adrenal DBI and the density of MDR but increased the rate of DBI processing, as determined by the HPLC profile of DBI-(17-50)-like immunoreactivity. The similar latency times for this effect and for ACTH stimulation of adrenal steroidogenesis suggest that the two processes are related. The ACTH-induced increase in both adrenal steroidogenesis and rate of DBI processing were completely inhibited by cycloheximide; this result suggests the requirement for the de novo synthesis of a protein with a short half-life, probably an endopeptidase. This enzyme, under the influence of ACTH, may activate formation of a DBI-processing product that stimulates steroidogenesis via the MDR. In support of this hypothesis is the demonstration that in hypophysectomized rats the MDR antagonist PK 11195 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide completely inhibited the adrenal steroidogenesis stimulated by ACTH and by the high-affinity MDR ligand 4'-chlorodiazepam.", "contents": "Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland. Diazepam-binding inhibitor (DBI) is a 9-kDa polypeptide that colocalizes in glial, adrenocortical, and Leydig cells with the mitochondrial DBI receptor (MDR). By binding with high affinity to the MDR, DBI and one of its processing products--DBI-(17-50)--regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH). In adrenals of hypophysectomized rats (1 day after surgery), ACTH failed to acutely affect the amount of adrenal DBI and the density of MDR but increased the rate of DBI processing, as determined by the HPLC profile of DBI-(17-50)-like immunoreactivity. The similar latency times for this effect and for ACTH stimulation of adrenal steroidogenesis suggest that the two processes are related. The ACTH-induced increase in both adrenal steroidogenesis and rate of DBI processing were completely inhibited by cycloheximide; this result suggests the requirement for the de novo synthesis of a protein with a short half-life, probably an endopeptidase. This enzyme, under the influence of ACTH, may activate formation of a DBI-processing product that stimulates steroidogenesis via the MDR. In support of this hypothesis is the demonstration that in hypophysectomized rats the MDR antagonist PK 11195 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide completely inhibited the adrenal steroidogenesis stimulated by ACTH and by the high-affinity MDR ligand 4'-chlorodiazepam."} {"id": "PMID:1279687", "title": "GTP-binding proteins inhibit cAMP activation of chloride channels in cystic fibrosis airway epithelial cells.", "content": "Cystic fibrosis (CF) is a genetic disease characterized, in part, by defective regulation of Cl- secretion by airway epithelial cells. In CF, cAMP does not activate Cl- channels in the apical membrane of airway epithelial cells. We report here whole-cell patch-clamp studies demonstrating that pertussis toxin, which uncouples heterotrimeric GTP-binding proteins (G proteins) from their receptors, and guanosine 5'-[beta-thio]diphosphate, which prevents G proteins from interacting with their effectors, increase Cl- currents and restore cAMP-activated Cl- currents in airway epithelial cells isolated from CF patients. In contrast, the G protein activators guanosine 5'-[gamma-thio]triphosphate and AlF4- reduce Cl- currents and inhibit cAMP from activating Cl- currents in normal airway epithelial cells. In CF cells treated with pertussis toxin or guanosine 5'-[beta-thio]diphosphate and in normal cells, cAMP activates a Cl- conductance that has properties similar to CF transmembrane-conductance regulator Cl- channels. We conclude that heterotrimeric G proteins inhibit cAMP-activated Cl- currents in airway epithelial cells and that modulation of the inhibitory G protein signaling pathway may have the therapeutic potential for improving cAMP-activated Cl- secretion in CF.", "contents": "GTP-binding proteins inhibit cAMP activation of chloride channels in cystic fibrosis airway epithelial cells. Cystic fibrosis (CF) is a genetic disease characterized, in part, by defective regulation of Cl- secretion by airway epithelial cells. In CF, cAMP does not activate Cl- channels in the apical membrane of airway epithelial cells. We report here whole-cell patch-clamp studies demonstrating that pertussis toxin, which uncouples heterotrimeric GTP-binding proteins (G proteins) from their receptors, and guanosine 5'-[beta-thio]diphosphate, which prevents G proteins from interacting with their effectors, increase Cl- currents and restore cAMP-activated Cl- currents in airway epithelial cells isolated from CF patients. In contrast, the G protein activators guanosine 5'-[gamma-thio]triphosphate and AlF4- reduce Cl- currents and inhibit cAMP from activating Cl- currents in normal airway epithelial cells. In CF cells treated with pertussis toxin or guanosine 5'-[beta-thio]diphosphate and in normal cells, cAMP activates a Cl- conductance that has properties similar to CF transmembrane-conductance regulator Cl- channels. We conclude that heterotrimeric G proteins inhibit cAMP-activated Cl- currents in airway epithelial cells and that modulation of the inhibitory G protein signaling pathway may have the therapeutic potential for improving cAMP-activated Cl- secretion in CF."} {"id": "PMID:1279688", "title": "Blocked early-stage latency in the peripheral blood cells of certain individuals infected with human immunodeficiency virus type 1.", "content": "Human immunodeficiency virus type 1 (HIV-1) infections of humans have a natural history characterized by a variable but usually slow progression to an immunodeficient state. We have described a molecular model of HIV-1 proviral latency in certain cell lines, characterized by extremely low or undetectable levels of unspliced genomic HIV-1-specific RNA but significant levels of multiply spliced HIV-1-specific RNA. We have utilized a quantitative reverse transcriptase-initiated polymerase chain reaction to measure the levels of various HIV-1 RNA species in peripheral blood mononuclear cells. The median level of multiply spliced HIV-1 RNA was dramatically higher than the median level of unspliced viral RNA in asymptomatic individuals. In addition, HIV-1 RNA patterns characterized by at least a 10-fold excess of multiply spliced to unspliced viral RNA were significantly more common in asymptomatic individuals than in patients with the acquired immunodeficiency syndrome. We suggest that asymptomatic clinical HIV-1 infection is characterized by a preponderance of HIV-1-infected peripheral blood cells blocked at an early stage of HIV-1 infection. This viral expression pattern, which we have called blocked early-stage latency, may constitute a reservoir of latently infected cells in certain HIV-1-infected persons.", "contents": "Blocked early-stage latency in the peripheral blood cells of certain individuals infected with human immunodeficiency virus type 1. Human immunodeficiency virus type 1 (HIV-1) infections of humans have a natural history characterized by a variable but usually slow progression to an immunodeficient state. We have described a molecular model of HIV-1 proviral latency in certain cell lines, characterized by extremely low or undetectable levels of unspliced genomic HIV-1-specific RNA but significant levels of multiply spliced HIV-1-specific RNA. We have utilized a quantitative reverse transcriptase-initiated polymerase chain reaction to measure the levels of various HIV-1 RNA species in peripheral blood mononuclear cells. The median level of multiply spliced HIV-1 RNA was dramatically higher than the median level of unspliced viral RNA in asymptomatic individuals. In addition, HIV-1 RNA patterns characterized by at least a 10-fold excess of multiply spliced to unspliced viral RNA were significantly more common in asymptomatic individuals than in patients with the acquired immunodeficiency syndrome. We suggest that asymptomatic clinical HIV-1 infection is characterized by a preponderance of HIV-1-infected peripheral blood cells blocked at an early stage of HIV-1 infection. This viral expression pattern, which we have called blocked early-stage latency, may constitute a reservoir of latently infected cells in certain HIV-1-infected persons."} {"id": "PMID:1279689", "title": "In vivo patterns of expression of urokinase and its inhibitor PAI-1 suggest a concerted role in regulating physiological angiogenesis.", "content": "To evaluate the role of plasminogen activators (PAs) in physiological angiogenesis, we have investigated the in vivo patterns of expression of urokinase-type PA (uPA) and PA-inhibitor type 1 (PAI-1) during neovascularization of ovarian follicles, the corpus luteum, and the maternal decidua. Using in situ hybridization, we detected uPA mRNA in the ovary along the route of capillary extension, originating at the existing ovarian vasculature, extending toward growing follicles, and terminating at the newly formed capillary sheaths surrounding each growing follicle. Following ovulation, uPA mRNA was expressed in capillary sprouts within the developing corpus luteum. During the process of decidual neovascularization, uPA expression was detected in endothelial cell cords traversing the maternal decidua in the direction of the newly implanted embryo. uPA mRNA was not detected in endothelial cells upon completion of neovascularization, suggesting that uPA expression is a part of the angiogenic response. During in vitro \"angiogenesis\" of cultured aortic explants, uPA was expressed in capillary sprouts but not in underlying endothelial cell sheets, suggesting that the expression of uPA depends on the histological context of the endothelial cell. Interestingly, during corpus luteum development and decidual neovascularization, and in aortic explants, PAI-1 expression was preferentially activated in cells in the vicinity of uPA-expressing capillary-like structures. These findings suggest a functional interplay between uPA- and PAI-1-expressing cells and support the idea that natural PA inhibitors function during angiogenesis to protect neovascularized tissues from excessive proteolysis.", "contents": "In vivo patterns of expression of urokinase and its inhibitor PAI-1 suggest a concerted role in regulating physiological angiogenesis. To evaluate the role of plasminogen activators (PAs) in physiological angiogenesis, we have investigated the in vivo patterns of expression of urokinase-type PA (uPA) and PA-inhibitor type 1 (PAI-1) during neovascularization of ovarian follicles, the corpus luteum, and the maternal decidua. Using in situ hybridization, we detected uPA mRNA in the ovary along the route of capillary extension, originating at the existing ovarian vasculature, extending toward growing follicles, and terminating at the newly formed capillary sheaths surrounding each growing follicle. Following ovulation, uPA mRNA was expressed in capillary sprouts within the developing corpus luteum. During the process of decidual neovascularization, uPA expression was detected in endothelial cell cords traversing the maternal decidua in the direction of the newly implanted embryo. uPA mRNA was not detected in endothelial cells upon completion of neovascularization, suggesting that uPA expression is a part of the angiogenic response. During in vitro \"angiogenesis\" of cultured aortic explants, uPA was expressed in capillary sprouts but not in underlying endothelial cell sheets, suggesting that the expression of uPA depends on the histological context of the endothelial cell. Interestingly, during corpus luteum development and decidual neovascularization, and in aortic explants, PAI-1 expression was preferentially activated in cells in the vicinity of uPA-expressing capillary-like structures. These findings suggest a functional interplay between uPA- and PAI-1-expressing cells and support the idea that natural PA inhibitors function during angiogenesis to protect neovascularized tissues from excessive proteolysis."} {"id": "PMID:1279690", "title": "Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells.", "content": "Fibroblast growth factor 1 (FGF-1) is a potent angiogenic and neurotrophic factor whose structure lacks a classical signal sequence for secretion. Although the initiation of these biological activities involves the interaction between FGF-1 and cell surface receptors, the mechanism responsible for the regulation of FGF-1 secretion is unknown. We report that murine NIH 3T3 cells transfected with a synthetic gene encoding FGF-1 secrete FGF-1 into their conditioned medium in response to heat shock. The form of FGF-1 released by NIH 3T3 cells in response to increased temperature (42 degrees C, 2 hr) in vitro is not biologically active and does not associate with either heparin or the extracellular NIH 3T3 monolayer matrix. However, it was possible to derive biologically active FGF-1 from the conditioned medium of heat-shocked NIH 3T3 cell transfectants by ammonium sulfate fractionation. The form of FGF-1 exposed by ammonium sulfate fractionation is similar in size to cytosolic FGF-1 and can bind and be eluted from immobilized heparin similarly to the recombinant human FGF-1 polypeptide. Further, the release of FGF-1 by NIH 3T3 cell transfectants in response to heat shock is reduced significantly by both actinomycin D and cycloheximide. These data indicate that increased temperature may upregulate the expression of a factor responsible for the secretion of FGF-1 as a biologically inactive complex that requires an activation step to exhibit the biological activity of the extracellular polypeptide mitogen.", "contents": "Heat shock induces the release of fibroblast growth factor 1 from NIH 3T3 cells. Fibroblast growth factor 1 (FGF-1) is a potent angiogenic and neurotrophic factor whose structure lacks a classical signal sequence for secretion. Although the initiation of these biological activities involves the interaction between FGF-1 and cell surface receptors, the mechanism responsible for the regulation of FGF-1 secretion is unknown. We report that murine NIH 3T3 cells transfected with a synthetic gene encoding FGF-1 secrete FGF-1 into their conditioned medium in response to heat shock. The form of FGF-1 released by NIH 3T3 cells in response to increased temperature (42 degrees C, 2 hr) in vitro is not biologically active and does not associate with either heparin or the extracellular NIH 3T3 monolayer matrix. However, it was possible to derive biologically active FGF-1 from the conditioned medium of heat-shocked NIH 3T3 cell transfectants by ammonium sulfate fractionation. The form of FGF-1 exposed by ammonium sulfate fractionation is similar in size to cytosolic FGF-1 and can bind and be eluted from immobilized heparin similarly to the recombinant human FGF-1 polypeptide. Further, the release of FGF-1 by NIH 3T3 cell transfectants in response to heat shock is reduced significantly by both actinomycin D and cycloheximide. These data indicate that increased temperature may upregulate the expression of a factor responsible for the secretion of FGF-1 as a biologically inactive complex that requires an activation step to exhibit the biological activity of the extracellular polypeptide mitogen."} {"id": "PMID:1279691", "title": "On \"genomenclature\": a comprehensive (and respectful) taxonomy for pseudogenes and other \"junk DNA\".", "content": "Genomic nomenclature has not kept pace with the levels and depth of analyzing and understanding genomic structure, function, and evolution. We wish to propose a general terminology that might aid the integrated study of evolution and molecular biology. Here we designate as a \"nuon\" any stretch of nucleic acid sequence that may be identifiable by any criterion. We show how such a general term will facilitate contemplation of the structural and functional contributions of such elements to the genome in its past, current, or future state. We focus in this paper on pseudogenes and dispersed repetitive elements, since their current names reflect the prevalent view that they constitute dispensable genomic noise (trash), rather than a vast repertoire of sequences with the capacity to shape an organism during evolution. This potential to contribute sequences for future use is reflected in the suggested terms \"potonuons\" or \"potogenes.\" If such a potonuon has been coopted into a variant or novel function, an evolutionary process termed \"exaptation,\" we employ the term \"xaptonuon.\" If a potonuon remains without function (nonaptive nuon), it is a \"nonaptation\" and we term it \"naptonuon.\" A number of examples for potonuons and xaptonuons are given.", "contents": "On \"genomenclature\": a comprehensive (and respectful) taxonomy for pseudogenes and other \"junk DNA\". Genomic nomenclature has not kept pace with the levels and depth of analyzing and understanding genomic structure, function, and evolution. We wish to propose a general terminology that might aid the integrated study of evolution and molecular biology. Here we designate as a \"nuon\" any stretch of nucleic acid sequence that may be identifiable by any criterion. We show how such a general term will facilitate contemplation of the structural and functional contributions of such elements to the genome in its past, current, or future state. We focus in this paper on pseudogenes and dispersed repetitive elements, since their current names reflect the prevalent view that they constitute dispensable genomic noise (trash), rather than a vast repertoire of sequences with the capacity to shape an organism during evolution. This potential to contribute sequences for future use is reflected in the suggested terms \"potonuons\" or \"potogenes.\" If such a potonuon has been coopted into a variant or novel function, an evolutionary process termed \"exaptation,\" we employ the term \"xaptonuon.\" If a potonuon remains without function (nonaptive nuon), it is a \"nonaptation\" and we term it \"naptonuon.\" A number of examples for potonuons and xaptonuons are given."} {"id": "PMID:1279692", "title": "Cloning and surface expression of Pseudomonas aeruginosa O antigen in Escherichia coli.", "content": "As a step toward developing recombinant oral vaccines, we have explored the feasibility of expression of O polysaccharide antigens from Pseudomonas aeruginosa by Escherichia coli. We cloned in E. coli HB101 a 26.2-kilobase DNA fragment from P. aeruginosa strain PA103 that specifies the production of the O polysaccharide of Fisher immunotype 2 (IT-2) strains. The recombinant organism incorporated the P. aeruginosa IT-2 O polysaccharide onto the core of the E. coli lipopolysaccharide (LPS). Transfer of the recombinant plasmid to three LPS-rough strains of P. aeruginosa resulted in synthesis of IT-2 O antigen, and two of these transconjugant strains also synthesized a second O polysaccharide, presumably representing expression of a repressed, or an incomplete, set of genes for an endogenous O polysaccharide. Rabbits injected with the purified recombinant LPS made antibody specific for P. aeruginosa IT-2 O side chains, as did mice fed the recombinant E. coli strain. Expression of P. aeruginosa O antigens by enteric bacteria makes it possible to study these recombinant strains as oral vaccines to prevent P. aeruginosa infections.", "contents": "Cloning and surface expression of Pseudomonas aeruginosa O antigen in Escherichia coli. As a step toward developing recombinant oral vaccines, we have explored the feasibility of expression of O polysaccharide antigens from Pseudomonas aeruginosa by Escherichia coli. We cloned in E. coli HB101 a 26.2-kilobase DNA fragment from P. aeruginosa strain PA103 that specifies the production of the O polysaccharide of Fisher immunotype 2 (IT-2) strains. The recombinant organism incorporated the P. aeruginosa IT-2 O polysaccharide onto the core of the E. coli lipopolysaccharide (LPS). Transfer of the recombinant plasmid to three LPS-rough strains of P. aeruginosa resulted in synthesis of IT-2 O antigen, and two of these transconjugant strains also synthesized a second O polysaccharide, presumably representing expression of a repressed, or an incomplete, set of genes for an endogenous O polysaccharide. Rabbits injected with the purified recombinant LPS made antibody specific for P. aeruginosa IT-2 O side chains, as did mice fed the recombinant E. coli strain. Expression of P. aeruginosa O antigens by enteric bacteria makes it possible to study these recombinant strains as oral vaccines to prevent P. aeruginosa infections."} {"id": "PMID:1279693", "title": "Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor.", "content": "We have isolated a cDNA from a mouse brain library that encodes a protein whose predicted amino acid sequence is 42% identical and 64% similar to that of the amyloid beta protein precursor (APP). This 653-amino acid protein, which we have termed the amyloid precursor-like protein (APLP), appears to be similar to APP in overall structure as well as amino acid sequence. The amino acid homologies are concentrated within three distinct regions of the two proteins where the identities are 47%, 54%, and 56%. The APLP cDNA hybridizes to two messages of approximately 2.4 and 1.6 kilobases that are present in mouse brain and neuroblastoma cells. Polyclonal antibodies raised against a peptide derived from the C terminus of APLP stain the cytoplasm in a pattern reminiscent of Golgi staining. In addition to APP, APLP also displays significant homology to the Drosophila APP-like protein APPL and a rat testes APP-like protein. These data indicate that the APP gene is a member of a strongly conserved gene family. Studies aimed at determining the functions of the proteins encoded by this gene family should provide valuable clues to their potential role in Alzheimer disease neuropathology.", "contents": "Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor. We have isolated a cDNA from a mouse brain library that encodes a protein whose predicted amino acid sequence is 42% identical and 64% similar to that of the amyloid beta protein precursor (APP). This 653-amino acid protein, which we have termed the amyloid precursor-like protein (APLP), appears to be similar to APP in overall structure as well as amino acid sequence. The amino acid homologies are concentrated within three distinct regions of the two proteins where the identities are 47%, 54%, and 56%. The APLP cDNA hybridizes to two messages of approximately 2.4 and 1.6 kilobases that are present in mouse brain and neuroblastoma cells. Polyclonal antibodies raised against a peptide derived from the C terminus of APLP stain the cytoplasm in a pattern reminiscent of Golgi staining. In addition to APP, APLP also displays significant homology to the Drosophila APP-like protein APPL and a rat testes APP-like protein. These data indicate that the APP gene is a member of a strongly conserved gene family. Studies aimed at determining the functions of the proteins encoded by this gene family should provide valuable clues to their potential role in Alzheimer disease neuropathology."} {"id": "PMID:1279694", "title": "Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities.", "content": "The spatial and temporal relationship between the polymerase and RNase H activities of human immunodeficiency virus type 1 reverse transcriptase has been examined by using a 40-mer RNA template and a series of DNA primers of lengths ranging from 15 to 40 nucleotides, hybridized to the RNA, as substrates. The experiments were executed in the absence and presence of heparin, an efficient trap to sequester any free or dissociated reverse transcriptase, thus facilitating the study of events associated with a single turnover of the enzyme. The results indicate a spatial separation of 18 or 19 nucleotides between the two sites. To examine the effect of concomitant polymerization on the RNase H activity, the substrate was doubly 5' end labeled on the RNA and DNA. This enabled the study of RNase H activity as a function of polymerization in a single experiment, and the results in the absence and presence of heparin indicate a tight temporal coupling between the two activities.", "contents": "Human immunodeficiency virus type 1 reverse transcriptase: spatial and temporal relationship between the polymerase and RNase H activities. The spatial and temporal relationship between the polymerase and RNase H activities of human immunodeficiency virus type 1 reverse transcriptase has been examined by using a 40-mer RNA template and a series of DNA primers of lengths ranging from 15 to 40 nucleotides, hybridized to the RNA, as substrates. The experiments were executed in the absence and presence of heparin, an efficient trap to sequester any free or dissociated reverse transcriptase, thus facilitating the study of events associated with a single turnover of the enzyme. The results indicate a spatial separation of 18 or 19 nucleotides between the two sites. To examine the effect of concomitant polymerization on the RNase H activity, the substrate was doubly 5' end labeled on the RNA and DNA. This enabled the study of RNase H activity as a function of polymerization in a single experiment, and the results in the absence and presence of heparin indicate a tight temporal coupling between the two activities."} {"id": "PMID:1279695", "title": "Mechanism of interferon action: autoregulation of RNA-dependent P1/eIF-2 alpha protein kinase (PKR) expression in transfected mammalian cells.", "content": "The expression of a molecular cDNA clone (P1 KIN) of the human RNA-dependent P1/eIF-2 alpha protein kinase (PKR) was examined in transfected monkey cells and in cell-free protein-synthesizing systems. Expression of the wild-type (wt) P1 KIN cDNA, which encodes an active protein kinase, was compared with that of the phosphotransfer catalytic domain II Lys-296-->Arg (K296R) mutant cDNA, which does not encode an active kinase. wt and K296R mutant P1 mRNAs prepared by transcription in vitro with T7 RNA polymerase programmed the cell-free synthesis of P1 ribosome-associated protein with comparable efficiency in the rabbit reticulocyte system. The K296R mutant P1 protein was also efficiently synthesized in vivo in transfected COS monkey cells. However, synthesis of the wt P1 protein was reduced about 30-fold in transfected COS cells as compared with the K296R mutant P1 protein. Cotransfection of wt P1 KIN cDNA with either K296R mutant P1 KIN cDNA or reovirus S4 cDNA greatly reduced the synthesis of K296R mutant P1 protein and reovirus sigma 3 protein, respectively. Although the wt and K296R mutant P1 KIN plasmid expression vectors replicated with comparable efficiencies in COS cells, the steady-state amount of P1 mRNA was about 3-fold less in COS cells transfected with the wt as compared with the K296R mutant P1 KIN cDNA. These results suggest that RNA-dependent P1 protein kinase expression is autoregulated in vivo in transfected mammalian cells primarily at the level of translation by a mechanism that is likely dependent upon catalytically active P1 kinase.", "contents": "Mechanism of interferon action: autoregulation of RNA-dependent P1/eIF-2 alpha protein kinase (PKR) expression in transfected mammalian cells. The expression of a molecular cDNA clone (P1 KIN) of the human RNA-dependent P1/eIF-2 alpha protein kinase (PKR) was examined in transfected monkey cells and in cell-free protein-synthesizing systems. Expression of the wild-type (wt) P1 KIN cDNA, which encodes an active protein kinase, was compared with that of the phosphotransfer catalytic domain II Lys-296-->Arg (K296R) mutant cDNA, which does not encode an active kinase. wt and K296R mutant P1 mRNAs prepared by transcription in vitro with T7 RNA polymerase programmed the cell-free synthesis of P1 ribosome-associated protein with comparable efficiency in the rabbit reticulocyte system. The K296R mutant P1 protein was also efficiently synthesized in vivo in transfected COS monkey cells. However, synthesis of the wt P1 protein was reduced about 30-fold in transfected COS cells as compared with the K296R mutant P1 protein. Cotransfection of wt P1 KIN cDNA with either K296R mutant P1 KIN cDNA or reovirus S4 cDNA greatly reduced the synthesis of K296R mutant P1 protein and reovirus sigma 3 protein, respectively. Although the wt and K296R mutant P1 KIN plasmid expression vectors replicated with comparable efficiencies in COS cells, the steady-state amount of P1 mRNA was about 3-fold less in COS cells transfected with the wt as compared with the K296R mutant P1 KIN cDNA. These results suggest that RNA-dependent P1 protein kinase expression is autoregulated in vivo in transfected mammalian cells primarily at the level of translation by a mechanism that is likely dependent upon catalytically active P1 kinase."} {"id": "PMID:1279696", "title": "Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression.", "content": "Recent studies have shown that there exists a family of protein kinases structurally and functionally related to the yeast cell cycle regulatory kinase cdc2 [Meyerson, M., Faha, B., Su, L.-K., Harlow, E. & Tsai, L.-H. (1991) Cold Spring Harbor Symp. Quant. Biol. 56, 177-186 and Meyerson, M., Enders, G. H., Wu, C.-L., Su, L.-K., Gorka, C., Nelson, C., Harlow, E. & Tsai, L.-H. (1992) EMBO J. 11, 2909-2917]. Two members of cdc2 family, p34cdc2 (also named cdk1) and cdk2, have been identified in mammalian cells. cdk1 kinase regulates the progression from G2 to M phase, and cdk2 kinase has been proposed to regulate the progression from G1 to S phase. In this work, we have cloned and structurally characterized a third member of the cdc2 kinase family with 58% amino acid sequence identity to mouse cdk1 and 61% identity to human cdk2. We call this kinase neuronal cdc2-like kinase (nclk) because, in contrast to either cdk1 or cdk2, nclk is expressed at high levels in terminally differentiated neurons no longer in the cell cycle. Previous studies have shown [Hisanaga, S., Kusubata, M., Okumura, E. & Kishimoto, T. (1991) J. Biol. Chem. 266, 21798-21803 and Guan, R. J., Hall, F. L. & Cohlberg, J. A. (1992) J. Neurochem. 58, 1365-1371] that cdk1 kinase, but not other structurally defined protein kinases, could phosphorylate the repeated Lys-Ser-Pro (KSP) motifs found in mammalian high and middle molecular mass neurofilament subunits in vitro, but the precise molecular nature of the endogenous neuronal KSP kinase has remained undefined. The structural similarity of nclk to cdk1 kinase and its high level of expression in terminally differentiated neurons suggest that nclk may play a role in the phosphorylation of the neurofilament KSP repeats in vivo, a function distinct from cell cycle regulation.", "contents": "Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression. Recent studies have shown that there exists a family of protein kinases structurally and functionally related to the yeast cell cycle regulatory kinase cdc2 [Meyerson, M., Faha, B., Su, L.-K., Harlow, E. & Tsai, L.-H. (1991) Cold Spring Harbor Symp. Quant. Biol. 56, 177-186 and Meyerson, M., Enders, G. H., Wu, C.-L., Su, L.-K., Gorka, C., Nelson, C., Harlow, E. & Tsai, L.-H. (1992) EMBO J. 11, 2909-2917]. Two members of cdc2 family, p34cdc2 (also named cdk1) and cdk2, have been identified in mammalian cells. cdk1 kinase regulates the progression from G2 to M phase, and cdk2 kinase has been proposed to regulate the progression from G1 to S phase. In this work, we have cloned and structurally characterized a third member of the cdc2 kinase family with 58% amino acid sequence identity to mouse cdk1 and 61% identity to human cdk2. We call this kinase neuronal cdc2-like kinase (nclk) because, in contrast to either cdk1 or cdk2, nclk is expressed at high levels in terminally differentiated neurons no longer in the cell cycle. Previous studies have shown [Hisanaga, S., Kusubata, M., Okumura, E. & Kishimoto, T. (1991) J. Biol. Chem. 266, 21798-21803 and Guan, R. J., Hall, F. L. & Cohlberg, J. A. (1992) J. Neurochem. 58, 1365-1371] that cdk1 kinase, but not other structurally defined protein kinases, could phosphorylate the repeated Lys-Ser-Pro (KSP) motifs found in mammalian high and middle molecular mass neurofilament subunits in vitro, but the precise molecular nature of the endogenous neuronal KSP kinase has remained undefined. The structural similarity of nclk to cdk1 kinase and its high level of expression in terminally differentiated neurons suggest that nclk may play a role in the phosphorylation of the neurofilament KSP repeats in vivo, a function distinct from cell cycle regulation."} {"id": "PMID:1279697", "title": "A host-inducible cytochrome P-450 from a host-specific caterpillar: molecular cloning and evolution.", "content": "Cytochrome P-450 monooxygenases (P-450s) play a critical role in the detoxification of natural and synthetic toxins in a wide range of organisms. We have isolated and sequenced cDNA clones encoding a P-450, CYP6B1, from larvae of Papilio polyxenes (Lepidoptera: Papilionidae), the black swallowtail butterfly. This P-450, cloned from a herbivorous insect, is highly inducible by xanthotoxin, a secondary metabolite abundant in the host plants of this specialized herbivore. On Northern blots, mRNAs crossreactive with CYP6B1 were detected in three Papilio species that, like the black swallowtail, have high levels of xanthotoxin-metabolic P-450 activity and encounter xanthotoxin or related compounds in their host plants; in contrast, no crossreactive mRNAs were detectable in three papilinid species that never encounter xanthotoxin in their host plants and lack detectable xanthotoxin-metabolic activity. These results provide evidence that new P-450s can arise as herbivores colonize different host plants and support the hypothesis that interactions between herbivores and their toxin-producing host plants have contributed to the diversification of the P-450 superfamily.", "contents": "A host-inducible cytochrome P-450 from a host-specific caterpillar: molecular cloning and evolution. Cytochrome P-450 monooxygenases (P-450s) play a critical role in the detoxification of natural and synthetic toxins in a wide range of organisms. We have isolated and sequenced cDNA clones encoding a P-450, CYP6B1, from larvae of Papilio polyxenes (Lepidoptera: Papilionidae), the black swallowtail butterfly. This P-450, cloned from a herbivorous insect, is highly inducible by xanthotoxin, a secondary metabolite abundant in the host plants of this specialized herbivore. On Northern blots, mRNAs crossreactive with CYP6B1 were detected in three Papilio species that, like the black swallowtail, have high levels of xanthotoxin-metabolic P-450 activity and encounter xanthotoxin or related compounds in their host plants; in contrast, no crossreactive mRNAs were detectable in three papilinid species that never encounter xanthotoxin in their host plants and lack detectable xanthotoxin-metabolic activity. These results provide evidence that new P-450s can arise as herbivores colonize different host plants and support the hypothesis that interactions between herbivores and their toxin-producing host plants have contributed to the diversification of the P-450 superfamily."} {"id": "PMID:1279698", "title": "Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures.", "content": "Exposure of primary cultures of neonatal rat cortical astrocytes to bacterial lipopolysaccharide (LPS) results in the appearance of nitric oxide synthase (NOS) activity. The induction of NOS, which is blocked by actinomycin D, is directly related to the duration of exposure and dose of LPS, and a 2-hr pulse can induce enzyme activity. Cytosol from LPS-treated astrocyte cultures, but not from control cultures, produces a Ca(2+)-independent conversion of L-arginine to L-citrulline that can be completely blocked by the specific NOS inhibitor NG-monomethyl-L-arginine. The induced NOS activity exhibits an apparent Km of 16.5 microM for L-arginine and is dependent on NADPH, FAD, and tetrahydrobiopterin. LPS also induces NOS in C6 glioma cells and microglial cultures but not in cultured cortical neurons. The expression of NOS in astrocytes and microglial cells has been confirmed by immunocytochemical staining using an antibody to the inducible NOS of mouse macrophages and by histochemical staining for NADPH diaphorase activity. We conclude that glial cells of the central nervous system can express an inducible form of NOS similar to the inducible NOS of macrophages. Inducible NOS in glia may, by generating nitric oxide, contribute to the neuronal damage associated with cerebral ischemia and/or demyelinating diseases.", "contents": "Induction of calcium-independent nitric oxide synthase activity in primary rat glial cultures. Exposure of primary cultures of neonatal rat cortical astrocytes to bacterial lipopolysaccharide (LPS) results in the appearance of nitric oxide synthase (NOS) activity. The induction of NOS, which is blocked by actinomycin D, is directly related to the duration of exposure and dose of LPS, and a 2-hr pulse can induce enzyme activity. Cytosol from LPS-treated astrocyte cultures, but not from control cultures, produces a Ca(2+)-independent conversion of L-arginine to L-citrulline that can be completely blocked by the specific NOS inhibitor NG-monomethyl-L-arginine. The induced NOS activity exhibits an apparent Km of 16.5 microM for L-arginine and is dependent on NADPH, FAD, and tetrahydrobiopterin. LPS also induces NOS in C6 glioma cells and microglial cultures but not in cultured cortical neurons. The expression of NOS in astrocytes and microglial cells has been confirmed by immunocytochemical staining using an antibody to the inducible NOS of mouse macrophages and by histochemical staining for NADPH diaphorase activity. We conclude that glial cells of the central nervous system can express an inducible form of NOS similar to the inducible NOS of macrophages. Inducible NOS in glia may, by generating nitric oxide, contribute to the neuronal damage associated with cerebral ischemia and/or demyelinating diseases."} {"id": "PMID:1279699", "title": "Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain.", "content": "Transport systems specific for L-glutamate and L-aspartate play an important role in the termination of neurotransmitter signals at excitatory synapses. We describe here the structure and function of a 66-kDa glycoprotein that was purified from rat brain and identified as an L-glutamate/L-aspartate transporter (GLAST). A GLAST-specific cDNA clone was isolated from a rat brain cDNA library. The cDNA insert encodes a polypeptide with 543 amino acid residues (59,697 Da). The amino acid sequence of GLAST suggests a distinctive structure and membrane topology, with some conserved motifs also present in prokaryotic glutamate transporters. The transporter function has been verified by amino acid uptake studies in the Xenopus laevis oocyte system. GLAST is specific for L-glutamate and L-aspartate, shows strict dependence on Na+ ions, and is inhibited by DL-threo-3-hydroxy-aspartate. In situ hybridization reveals a strikingly high density of GLAST mRNA in the Purkinje cell layer of cerebellum, presumably in the Bergmann glia cells, and a less dense distribution throughout the cerebrum. These data suggest that GLAST may be involved in the regulation of neurotransmitter concentration in central nervous system.", "contents": "Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain. Transport systems specific for L-glutamate and L-aspartate play an important role in the termination of neurotransmitter signals at excitatory synapses. We describe here the structure and function of a 66-kDa glycoprotein that was purified from rat brain and identified as an L-glutamate/L-aspartate transporter (GLAST). A GLAST-specific cDNA clone was isolated from a rat brain cDNA library. The cDNA insert encodes a polypeptide with 543 amino acid residues (59,697 Da). The amino acid sequence of GLAST suggests a distinctive structure and membrane topology, with some conserved motifs also present in prokaryotic glutamate transporters. The transporter function has been verified by amino acid uptake studies in the Xenopus laevis oocyte system. GLAST is specific for L-glutamate and L-aspartate, shows strict dependence on Na+ ions, and is inhibited by DL-threo-3-hydroxy-aspartate. In situ hybridization reveals a strikingly high density of GLAST mRNA in the Purkinje cell layer of cerebellum, presumably in the Bergmann glia cells, and a less dense distribution throughout the cerebrum. These data suggest that GLAST may be involved in the regulation of neurotransmitter concentration in central nervous system."} {"id": "PMID:1279700", "title": "Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes.", "content": "Using an FK506 affinity column to identify mammalian immunosuppressant-binding proteins, we identified an immunophilin with an apparent M(r) approximately 55,000, which we have named FKBP52. We used chemically determined peptide sequence and a computerized algorithm to search GenPept, the translated GenBank data base, and identified two cDNAs likely to encode the murine FKBP52 homolog. We amplified a murine cDNA fragment, used it to select a human FKBP52 (hFKBP52) cDNA clone, and then used the clone to deduce the hFKBP52 sequence (calculated M(r) 51,810) and to express hFKBP52 in Escherichia coli. Recombinant hFKBP52 has peptidyl-prolyl cis-trans isomerase activity that is inhibited by FK506 and rapamycin and an FKBP12-like consensus sequence that probably defines the immunosuppressant-binding site. FKBP52 is apparently common to several vertebrate species and associates with the 90-kDa heat shock protein (hsp90) in untransformed mammalian steroid receptor complexes. The putative immunosuppressant-binding site is probably distinct from the hsp90-binding site, and we predict that FKBP52 has different structural domains to accommodate these functions. hFKBP52 contains 12 protein kinase phosphorylation-site motifs and a potential calmodulin-binding site, implying that posttranslational phosphorylation could generate multiple isoforms of the protein and that calmodulin and intracellular Ca2+ levels could affect FKBP52 function. FKBP52 transcripts are present in a variety of human tissues and could vary in abundance and/or stability.", "contents": "Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes. Using an FK506 affinity column to identify mammalian immunosuppressant-binding proteins, we identified an immunophilin with an apparent M(r) approximately 55,000, which we have named FKBP52. We used chemically determined peptide sequence and a computerized algorithm to search GenPept, the translated GenBank data base, and identified two cDNAs likely to encode the murine FKBP52 homolog. We amplified a murine cDNA fragment, used it to select a human FKBP52 (hFKBP52) cDNA clone, and then used the clone to deduce the hFKBP52 sequence (calculated M(r) 51,810) and to express hFKBP52 in Escherichia coli. Recombinant hFKBP52 has peptidyl-prolyl cis-trans isomerase activity that is inhibited by FK506 and rapamycin and an FKBP12-like consensus sequence that probably defines the immunosuppressant-binding site. FKBP52 is apparently common to several vertebrate species and associates with the 90-kDa heat shock protein (hsp90) in untransformed mammalian steroid receptor complexes. The putative immunosuppressant-binding site is probably distinct from the hsp90-binding site, and we predict that FKBP52 has different structural domains to accommodate these functions. hFKBP52 contains 12 protein kinase phosphorylation-site motifs and a potential calmodulin-binding site, implying that posttranslational phosphorylation could generate multiple isoforms of the protein and that calmodulin and intracellular Ca2+ levels could affect FKBP52 function. FKBP52 transcripts are present in a variety of human tissues and could vary in abundance and/or stability."} {"id": "PMID:1279701", "title": "Signal-mediated nuclear transport in simian virus 40-transformed cells is regulated by large tumor antigen.", "content": "Transformation of cultured cells with simian virus 40 (SV40), or transfection with the early region of the SV40 genome, causes a significant increase in both the rate of signal-mediated nuclear transport and the functional size of the transport channels (located in the pore complexes). By microinjecting purified large tumor (T) antigen into the cytoplasm of murine BALB/c 3T3 cells, we have demonstrated that this protein alone can account for the increase in transport capacity. The T antigen-dependent changes can be partially inhibited by cycloheximide and require a functional nuclear localization sequence. Although necessary, the nuclear localization sequence by itself cannot produce the observed variations in nuclear permeability and presumably function in a \"helper\" capacity, in association with another, as yet unidentified domain.", "contents": "Signal-mediated nuclear transport in simian virus 40-transformed cells is regulated by large tumor antigen. Transformation of cultured cells with simian virus 40 (SV40), or transfection with the early region of the SV40 genome, causes a significant increase in both the rate of signal-mediated nuclear transport and the functional size of the transport channels (located in the pore complexes). By microinjecting purified large tumor (T) antigen into the cytoplasm of murine BALB/c 3T3 cells, we have demonstrated that this protein alone can account for the increase in transport capacity. The T antigen-dependent changes can be partially inhibited by cycloheximide and require a functional nuclear localization sequence. Although necessary, the nuclear localization sequence by itself cannot produce the observed variations in nuclear permeability and presumably function in a \"helper\" capacity, in association with another, as yet unidentified domain."} {"id": "PMID:1279702", "title": "Characterization of the precursor for Manduca sexta diuretic hormone Mas-DH.", "content": "We have isolated a cDNA clone encoding a precursor form of the diuretic hormone from the tobacco hornworm Manduca sexta (Mas-DH). Translation of the cDNA revealed a 138-amino acid precursor consisting of the Mas-DH amino acid sequence bounded by dibasic amino acid processing sites, a putative signal sequence, and additional peptide sequence on either side of the Mas-DH coding sequence. The region of the precursor upstream of the mature Mas-DH sequence shows limited (28%) homology to the cryptic region of the ovine corticotropin-releasing factor precursor. The Mas-DH RNA is 1.5-1.6 kilobases long; it is present in both the heads and bodies of adult and larval insects. In prewandering fifth stadium larvae, Mas-DH mRNA is expressed in brain, nerve cord, gut, and Malpighian tubules, but not in the fat body. There is a single genomic copy of the Mas-DH gene; the message is multiply spliced.", "contents": "Characterization of the precursor for Manduca sexta diuretic hormone Mas-DH. We have isolated a cDNA clone encoding a precursor form of the diuretic hormone from the tobacco hornworm Manduca sexta (Mas-DH). Translation of the cDNA revealed a 138-amino acid precursor consisting of the Mas-DH amino acid sequence bounded by dibasic amino acid processing sites, a putative signal sequence, and additional peptide sequence on either side of the Mas-DH coding sequence. The region of the precursor upstream of the mature Mas-DH sequence shows limited (28%) homology to the cryptic region of the ovine corticotropin-releasing factor precursor. The Mas-DH RNA is 1.5-1.6 kilobases long; it is present in both the heads and bodies of adult and larval insects. In prewandering fifth stadium larvae, Mas-DH mRNA is expressed in brain, nerve cord, gut, and Malpighian tubules, but not in the fat body. There is a single genomic copy of the Mas-DH gene; the message is multiply spliced."} {"id": "PMID:1279703", "title": "A new look at the mechanism of activation and inactivation of voltage-gated ion channels.", "content": "Studies on the kinetics of activation and inactivation of the sodium channels of the squid giant axon, on the sodium gating current, and on the properties of the non-inactivating steady-state current, are briefly reviewed. Taken in conjunction with recent evidence on the structure of voltage-gated ion channels, they have led to the development of a series-parallel model of the sodium channel that can be regarded as a modernized version of the Hodgkin-Huxley model, with some novel features. It is suggested that activation results from conformational changes brought about by the four S4 voltage sensors operating in parallel, each of which makes two discrete steps to reach the fully activated state of the channel. There follows a voltage-independent hydration step, and the channel is ready to open. Inactivation is a potential-dependent process involving a third transition of voltage sensor S4d alone, which, rather than bringing a ball and chain blocking group into position to close the channels, serves to switch the system so that it passes from an initial activated mode, in which there is a high probability of arriving at an open state with a brief latency, to a second steady-state mode, in which the probability of opening is very much lower.", "contents": "A new look at the mechanism of activation and inactivation of voltage-gated ion channels. Studies on the kinetics of activation and inactivation of the sodium channels of the squid giant axon, on the sodium gating current, and on the properties of the non-inactivating steady-state current, are briefly reviewed. Taken in conjunction with recent evidence on the structure of voltage-gated ion channels, they have led to the development of a series-parallel model of the sodium channel that can be regarded as a modernized version of the Hodgkin-Huxley model, with some novel features. It is suggested that activation results from conformational changes brought about by the four S4 voltage sensors operating in parallel, each of which makes two discrete steps to reach the fully activated state of the channel. There follows a voltage-independent hydration step, and the channel is ready to open. Inactivation is a potential-dependent process involving a third transition of voltage sensor S4d alone, which, rather than bringing a ball and chain blocking group into position to close the channels, serves to switch the system so that it passes from an initial activated mode, in which there is a high probability of arriving at an open state with a brief latency, to a second steady-state mode, in which the probability of opening is very much lower."} {"id": "PMID:1279704", "title": "Cortical astrocytes activated by basic fibroblast growth factor secrete molecules that stimulate differentiation of mesencephalic dopaminergic neurons.", "content": "In reactive gliosis, astrocytes undergo morphological and biochemical changes which can be mimicked in vitro by treatment with bFGF (basic fibroblast growth factor) or cAMP. To investigate the influence of activated cortical astrocytes on central nervous system (CNSD) neurons, we studied the effect of the supernatant from bFGF-treated astrocytes on the development of dopaminergic neurons from rat mesencephalon. Conditioned medium of untreated astrocytes stimulated dopamine uptake of mesencephalic cultures. After activation of astrocytes with bFGF this effect was greatly enhanced. It was significantly more potent than stimulating effects of other neurotrophic factors. The supernatant of these astrocytes increased the biochemical differentiation but not the survival of dopaminergic neurons in our cell culture system. Trypsin digestion and gel chromatography revealed that the activity was due to one or several proteins with molecular mass above 5 kDa. We excluded the participation of several factors known to be produced by astrocytes or that are neurotrophic for substantia nigra cultures. In particular, we provide evidence that bFGF, BDNF, NT-3, Il-1, Il-6, S100 beta and alpha 2-macroglobulin were not involved in the effect of the conditioned medium. In vitro stimulation of astrocytes therefore triggers the expression of currently uncharacterized factors which influence the biochemical differentiation of mesencephalic dopaminergic neurons, the cells that degenerate in Parkinson's disease.", "contents": "Cortical astrocytes activated by basic fibroblast growth factor secrete molecules that stimulate differentiation of mesencephalic dopaminergic neurons. In reactive gliosis, astrocytes undergo morphological and biochemical changes which can be mimicked in vitro by treatment with bFGF (basic fibroblast growth factor) or cAMP. To investigate the influence of activated cortical astrocytes on central nervous system (CNSD) neurons, we studied the effect of the supernatant from bFGF-treated astrocytes on the development of dopaminergic neurons from rat mesencephalon. Conditioned medium of untreated astrocytes stimulated dopamine uptake of mesencephalic cultures. After activation of astrocytes with bFGF this effect was greatly enhanced. It was significantly more potent than stimulating effects of other neurotrophic factors. The supernatant of these astrocytes increased the biochemical differentiation but not the survival of dopaminergic neurons in our cell culture system. Trypsin digestion and gel chromatography revealed that the activity was due to one or several proteins with molecular mass above 5 kDa. We excluded the participation of several factors known to be produced by astrocytes or that are neurotrophic for substantia nigra cultures. In particular, we provide evidence that bFGF, BDNF, NT-3, Il-1, Il-6, S100 beta and alpha 2-macroglobulin were not involved in the effect of the conditioned medium. In vitro stimulation of astrocytes therefore triggers the expression of currently uncharacterized factors which influence the biochemical differentiation of mesencephalic dopaminergic neurons, the cells that degenerate in Parkinson's disease."} {"id": "PMID:1279705", "title": "Asymmetry of the rat acetylcholine receptor subunits in the narrow region of the pore.", "content": "The acetylcholine receptor (AChR) channel is a pentameric protein in which every subunit contributes to the conducting parts of the pore. Recent studies of rat nicotinic AChR channels mutated in the alpha-subunit revealed that a threonine residue (alpha T264) in the transmembrane segment M2 forms part of the narrow region of the channel. We have mutated the residues at homologous positions in the beta-, gamma-, and delta-subunits and measured the resulting change in channel conductance. For all subunits the conductance is inversely related to the volume of the amino acid residue, suggesting that they form part of the channel narrow region. Exchanges of residues between subunits do not alter the conductance, suggesting a ring-like structure formed by homologous amino acids. To investigate the relative contribution of amino acid residues at these positions in determining the channel conductance, receptors carrying the same amino acid in each subunit in the narrow region were constructed. They form functional channels in which the conductance is inversely related to the volume of the amino acids in the narrow region. Channels in which the narrow region is formed by four serines and one valine have the same conductance if the valine is located in the alpha-, beta-, or gamma-subunits, but it is smaller if the valine is located in the delta-subunit. The results suggest a structural asymmetry of the AChR channel in its narrow region formed by the hydroxylated amino acids of alpha-, gamma- and delta-subunits, where the delta-subunit serine is a main determinant of the channel conductance.", "contents": "Asymmetry of the rat acetylcholine receptor subunits in the narrow region of the pore. The acetylcholine receptor (AChR) channel is a pentameric protein in which every subunit contributes to the conducting parts of the pore. Recent studies of rat nicotinic AChR channels mutated in the alpha-subunit revealed that a threonine residue (alpha T264) in the transmembrane segment M2 forms part of the narrow region of the channel. We have mutated the residues at homologous positions in the beta-, gamma-, and delta-subunits and measured the resulting change in channel conductance. For all subunits the conductance is inversely related to the volume of the amino acid residue, suggesting that they form part of the channel narrow region. Exchanges of residues between subunits do not alter the conductance, suggesting a ring-like structure formed by homologous amino acids. To investigate the relative contribution of amino acid residues at these positions in determining the channel conductance, receptors carrying the same amino acid in each subunit in the narrow region were constructed. They form functional channels in which the conductance is inversely related to the volume of the amino acids in the narrow region. Channels in which the narrow region is formed by four serines and one valine have the same conductance if the valine is located in the alpha-, beta-, or gamma-subunits, but it is smaller if the valine is located in the delta-subunit. The results suggest a structural asymmetry of the AChR channel in its narrow region formed by the hydroxylated amino acids of alpha-, gamma- and delta-subunits, where the delta-subunit serine is a main determinant of the channel conductance."} {"id": "PMID:1279730", "title": "Isolation and mass spectrometric identification of two metabolites of FK 506 from rat liver microsomal incubation media.", "content": "A transient epoxide in equilibrium with its possible isomeric forms, most probably induced easily by neighboring-group assistance of a hydroxy group, and a dihydrodiol formed under the influence of the hydrase enzymic activity and/or by simple hydrolysis were isolated by HPLC and identified by FAB/MS from rat liver microsomal incubation media.", "contents": "Isolation and mass spectrometric identification of two metabolites of FK 506 from rat liver microsomal incubation media. A transient epoxide in equilibrium with its possible isomeric forms, most probably induced easily by neighboring-group assistance of a hydroxy group, and a dihydrodiol formed under the influence of the hydrase enzymic activity and/or by simple hydrolysis were isolated by HPLC and identified by FAB/MS from rat liver microsomal incubation media."} {"id": "PMID:1279731", "title": "Interactions of prostanoids with the platelet activating factors.", "content": "The platelet-activating factor (PAF) induced a marked increase of the thromboxane (TX) B2-formation in the incubation medium of isolated myocardium and tissue from other organs. The content of the 6-oxo-prostaglandin (PG)F1 alpha, the inactive metabolite of PGI2, remained uninfluenced or showed a small decrease. PAF, given in a concentration of 2.10(-9) mol/l or a single dose of 100 ng, significantly reduced the contraction force and the coronary flow of isolated guinea-pig hearts. This effect was connected with a high efflux of TXA2. The PAF-antagonist, WEB 2086, nearly abolished the cardiac effects of PAF, and iloprost or a pretreatment with indomethacin markedly reduced the PAF-influence on the heart. The TXA2-antagonist BM 13177 was ineffective. The results indicate a close interaction between the myocardial PAF-effect and the TXA2-formation of the heart tissue, but gave no suggestion for a mediation of the PAF-effect by TXA2. The PAF-antagonistic action of WEB 2086, iloprost and indomethacin could be of some interest in the therapy of cardiovasculatory diseases.", "contents": "Interactions of prostanoids with the platelet activating factors. The platelet-activating factor (PAF) induced a marked increase of the thromboxane (TX) B2-formation in the incubation medium of isolated myocardium and tissue from other organs. The content of the 6-oxo-prostaglandin (PG)F1 alpha, the inactive metabolite of PGI2, remained uninfluenced or showed a small decrease. PAF, given in a concentration of 2.10(-9) mol/l or a single dose of 100 ng, significantly reduced the contraction force and the coronary flow of isolated guinea-pig hearts. This effect was connected with a high efflux of TXA2. The PAF-antagonist, WEB 2086, nearly abolished the cardiac effects of PAF, and iloprost or a pretreatment with indomethacin markedly reduced the PAF-influence on the heart. The TXA2-antagonist BM 13177 was ineffective. The results indicate a close interaction between the myocardial PAF-effect and the TXA2-formation of the heart tissue, but gave no suggestion for a mediation of the PAF-effect by TXA2. The PAF-antagonistic action of WEB 2086, iloprost and indomethacin could be of some interest in the therapy of cardiovasculatory diseases."} {"id": "PMID:1279732", "title": "Effects of a newly synthesized leukotriene antagonist, NZ-107, on immediate-type hypersensitivity reaction in rats and guinea-pigs.", "content": "The effects of 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone (NZ-107) on immediate type hypersensitivity reactions in rats and guinea-pigs were studied. 1. When NZ-107, at a dose of 50 mg/kg (i.p.) or 100 mg/kg (orally), was administered to rats, 48-h homologous passive cutaneous anaphylaxis (PCA) reaction and histamine-, leukotriene C4 (LTC4)- and leukotriene D4 (LTD4)-induced skin reactions were suppressed by the agent. 2. NZ-107 (10(-6) g/ml) inhibited both LTC4- and LTD4-induced contractions of isolated rat stomach smooth muscle. 3. NZ-107 inhibited antigen-induced histamine release from rat peritoneal mast cells by 26% at a concentration of 10(-4) g/ml. 4. NZ-107, at doses of 25 and 50 mg/kg (orally), significantly inhibited guinea-pig 3-h heterologous PCA reaction. 5. NZ-107 inhibited antigen-induced histamine release from guinea-pig lung tissue by 17% and 48% at concentrations of 5 x 10(-5) and 10(-4) g/ml, respectively. 6. NZ-107, at doses of 25 and 50 mg/kg (i.p.), inhibited antigen-induced bronchoconstriction and eosinophil accumulation in the bronchoalveolar lavage fluid (BALF) of guinea-pigs. These results suggest that NZ-107 has anti-allergic action including inhibition of eosinophil accumulation in an antigen-challenged airway lesion in rats and guinea-pigs. The anti-allergic action of this agent is thought to be due to its action as a histamine and LT antagonist and its consequent inhibition of antigen-induced histamine release.", "contents": "Effects of a newly synthesized leukotriene antagonist, NZ-107, on immediate-type hypersensitivity reaction in rats and guinea-pigs. The effects of 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone (NZ-107) on immediate type hypersensitivity reactions in rats and guinea-pigs were studied. 1. When NZ-107, at a dose of 50 mg/kg (i.p.) or 100 mg/kg (orally), was administered to rats, 48-h homologous passive cutaneous anaphylaxis (PCA) reaction and histamine-, leukotriene C4 (LTC4)- and leukotriene D4 (LTD4)-induced skin reactions were suppressed by the agent. 2. NZ-107 (10(-6) g/ml) inhibited both LTC4- and LTD4-induced contractions of isolated rat stomach smooth muscle. 3. NZ-107 inhibited antigen-induced histamine release from rat peritoneal mast cells by 26% at a concentration of 10(-4) g/ml. 4. NZ-107, at doses of 25 and 50 mg/kg (orally), significantly inhibited guinea-pig 3-h heterologous PCA reaction. 5. NZ-107 inhibited antigen-induced histamine release from guinea-pig lung tissue by 17% and 48% at concentrations of 5 x 10(-5) and 10(-4) g/ml, respectively. 6. NZ-107, at doses of 25 and 50 mg/kg (i.p.), inhibited antigen-induced bronchoconstriction and eosinophil accumulation in the bronchoalveolar lavage fluid (BALF) of guinea-pigs. These results suggest that NZ-107 has anti-allergic action including inhibition of eosinophil accumulation in an antigen-challenged airway lesion in rats and guinea-pigs. The anti-allergic action of this agent is thought to be due to its action as a histamine and LT antagonist and its consequent inhibition of antigen-induced histamine release."} {"id": "PMID:1279733", "title": "Asymptotic distributions of apparent open times and shut times in a single channel record allowing for the omission of brief events.", "content": "The openings and shuttings of individual ion channel molecules can be described by a Markov process with discrete states in continuous time. The predicted distributions of the durations of open times, shut times, bursts of openings, etc. are all described, in principle, by mixtures of exponential densities. In practice it is usually found that some of the open times, and the shut times, are too short to be detected reliably. If a fixed dead-time tau is assumed then it is possible to define, as an approximation to what is actually observed, an 'extended opening' or e-opening which starts with an opening of duration at least tau followed by any number of openings and shuttings, all the shut times being shorter than tau; the e-opening ends when a shut time longer than tau occurs. A similar definition is used for e-shut times. The probability densities, f(t), of these extended times have previously been obtained as expressions which become progressively more complicated, and numerically unstable to compute, as t-->infinity. In this paper we present, for the two-state model, an alternative representation as an infinite series of which a small number of terms gives a very accurate approximation of f (t) for large t. For the general model we present an asymptotic representation as a mixture of exponentials which is accurate for all except quite small values of t. Some simple model-independent corrections for missed events are discussed in relationship to the exact solutions.", "contents": "Asymptotic distributions of apparent open times and shut times in a single channel record allowing for the omission of brief events. The openings and shuttings of individual ion channel molecules can be described by a Markov process with discrete states in continuous time. The predicted distributions of the durations of open times, shut times, bursts of openings, etc. are all described, in principle, by mixtures of exponential densities. In practice it is usually found that some of the open times, and the shut times, are too short to be detected reliably. If a fixed dead-time tau is assumed then it is possible to define, as an approximation to what is actually observed, an 'extended opening' or e-opening which starts with an opening of duration at least tau followed by any number of openings and shuttings, all the shut times being shorter than tau; the e-opening ends when a shut time longer than tau occurs. A similar definition is used for e-shut times. The probability densities, f(t), of these extended times have previously been obtained as expressions which become progressively more complicated, and numerically unstable to compute, as t-->infinity. In this paper we present, for the two-state model, an alternative representation as an infinite series of which a small number of terms gives a very accurate approximation of f (t) for large t. For the general model we present an asymptotic representation as a mixture of exponentials which is accurate for all except quite small values of t. Some simple model-independent corrections for missed events are discussed in relationship to the exact solutions."} {"id": "PMID:1279734", "title": "Long-range afferents in the rat spinal cord. II. Arborizations that penetrate grey matter.", "content": "1. The caudal extent of the collateral arborizations of entering sensory fibres in rat spinal cord was investigated by two methods: bulk labelling of peripheral nerves by injection of horseradish peroxidase conjugated to cholera toxin (B-HRP) and by antidromic stimulation using small currents from microelectrodes in the spinal cord while recording from single units in peripheral nerve or dorsal root. 2. The results show that injection of B-HRP into the sural or sciatic nerve labelled sural afferents in the grey matter three to four segments caudal to their root entry and sciatic nerve fibres were located in S4, the most caudal segment examined, four to six segments caudal to their root entry. 3. Detailed mapping with microelectrode stimulation showed that the parent descending fibres from filaments dissected from the L1 dorsal root coursed more than 20 mm, seven to eight segments caudal to the entry point in the dorsal columns and sent branches into the grey matter. Single units from the sural nerve were also followed caudally into the S2 and S3 spinal cord segments and also issued collateral branches into the grey matter. 4. The present results suggest that there is close agreement in the caudal penetration of long-ranging afferents by using complementary anatomical and electrophysiological methods.", "contents": "Long-range afferents in the rat spinal cord. II. Arborizations that penetrate grey matter. 1. The caudal extent of the collateral arborizations of entering sensory fibres in rat spinal cord was investigated by two methods: bulk labelling of peripheral nerves by injection of horseradish peroxidase conjugated to cholera toxin (B-HRP) and by antidromic stimulation using small currents from microelectrodes in the spinal cord while recording from single units in peripheral nerve or dorsal root. 2. The results show that injection of B-HRP into the sural or sciatic nerve labelled sural afferents in the grey matter three to four segments caudal to their root entry and sciatic nerve fibres were located in S4, the most caudal segment examined, four to six segments caudal to their root entry. 3. Detailed mapping with microelectrode stimulation showed that the parent descending fibres from filaments dissected from the L1 dorsal root coursed more than 20 mm, seven to eight segments caudal to the entry point in the dorsal columns and sent branches into the grey matter. Single units from the sural nerve were also followed caudally into the S2 and S3 spinal cord segments and also issued collateral branches into the grey matter. 4. The present results suggest that there is close agreement in the caudal penetration of long-ranging afferents by using complementary anatomical and electrophysiological methods."} {"id": "PMID:1279736", "title": "Molecular determinants of channel function.", "content": "The 40 years since the seminal papers of Hodgkin and Huxley appeared have been extraordinarily productive in terms of understanding the molecular basis for electrical activity. The Hodgkin-Huxley proposal that electrical excitability should be understood in terms of voltage-dependent changes in discrete sites has been resoundingly verified. Indeed, the Hodgkin-Huxley framework is remarkable in that its essential elements have remained largely intact as molecular understanding has advanced. This robustness is, at least in part, a result of the fact that Hodgkin and Huxley developed a mathematical model, based on simple physical arguments, that was sufficiently comprehensive to describe the kinetics of the voltage-clamped currents and yet simple enough to be predictive. The predictive features were demonstrated early by the reconstruction of both space-clamped and propagated action potentials on a desk-top calculator (293) and, later, when the sites of Hodgkin and Huxley developed into being well-characterized molecular structures. Voltage- and ligand-dependent ion-selective channels are now the established framework within which cellular electrophysiology is being pursued. Moreover, electrophysiological measurements of membrane and single-channel currents have become essential tools to examine molecular questions pertaining to channel structure and activity. The last 10 years have witnessed spectacular activity, which has resulted from two developments, the giga-seal patch clamp (249) and the elucidation of primary sequences of a number of channel-forming proteins (494), along with the first outlines of their low-resolution three-dimensional structures (651). The stage is now set for 1) applying a variety of convergent techniques to decipher molecular structural details at high resolution, and 2) seeking to understand the complex dynamic functions, gating, and ion selectivity at the molecular level. The early successes are likely to be in understanding the molecular determinants of ion conductance and selectivity, initially in terms of quantitative descriptions of how a sequence modification can alter a channel's permeability characteristics. Channel gating is a far more elusive target because it involves molecular rearrangements, which are poorly understood at any level of description and which may be modified by the channel's environment. The general mechanisms of ion permeation and gating will differ among different classes of ion channels, but a molecular understanding of either phenomenon must eventually be based on an understanding of intermolecular forces, which are invariant among all channel types.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Molecular determinants of channel function. The 40 years since the seminal papers of Hodgkin and Huxley appeared have been extraordinarily productive in terms of understanding the molecular basis for electrical activity. The Hodgkin-Huxley proposal that electrical excitability should be understood in terms of voltage-dependent changes in discrete sites has been resoundingly verified. Indeed, the Hodgkin-Huxley framework is remarkable in that its essential elements have remained largely intact as molecular understanding has advanced. This robustness is, at least in part, a result of the fact that Hodgkin and Huxley developed a mathematical model, based on simple physical arguments, that was sufficiently comprehensive to describe the kinetics of the voltage-clamped currents and yet simple enough to be predictive. The predictive features were demonstrated early by the reconstruction of both space-clamped and propagated action potentials on a desk-top calculator (293) and, later, when the sites of Hodgkin and Huxley developed into being well-characterized molecular structures. Voltage- and ligand-dependent ion-selective channels are now the established framework within which cellular electrophysiology is being pursued. Moreover, electrophysiological measurements of membrane and single-channel currents have become essential tools to examine molecular questions pertaining to channel structure and activity. The last 10 years have witnessed spectacular activity, which has resulted from two developments, the giga-seal patch clamp (249) and the elucidation of primary sequences of a number of channel-forming proteins (494), along with the first outlines of their low-resolution three-dimensional structures (651). The stage is now set for 1) applying a variety of convergent techniques to decipher molecular structural details at high resolution, and 2) seeking to understand the complex dynamic functions, gating, and ion selectivity at the molecular level. The early successes are likely to be in understanding the molecular determinants of ion conductance and selectivity, initially in terms of quantitative descriptions of how a sequence modification can alter a channel's permeability characteristics. Channel gating is a far more elusive target because it involves molecular rearrangements, which are poorly understood at any level of description and which may be modified by the channel's environment. The general mechanisms of ion permeation and gating will differ among different classes of ion channels, but a molecular understanding of either phenomenon must eventually be based on an understanding of intermolecular forces, which are invariant among all channel types.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1279737", "title": "Insulin-like growth factors (IGFs): implications for aging.", "content": "The insulin-like growth factors (IGF)-I and IGF-II are peptides with structural homology to insulin and potent mitogenic and anabolic actions in vitro and in vivo. IGF-I levels are growth hormone (GH)-dependent and vary strikingly with age. IGF-I levels are typically low in infancy and childhood, increase dramatically during puberty, and then gradually decline with advancing age. Whether age-associated changes in GH production or sex steroid secretion, or other unknown factors, cause diminished IGF production in the elderly remains to be determined. In the brain, IGF-II appears to be the most prevalent IGF, but a truncated form of IGF-I also has been recognized. IGF actions are mediated by binding to a family of receptors, which includes the insulin receptor, the structurally homologous type I IGF receptor, and the IGF-II/M-6P receptor, all of which are found in the central nervous system. Additionally, the IGFs bind with high affinity to a family of IGF-binding proteins (IGFBPs). Of the six known IGFBPs, IGFBP-2 appears to be the major one in the mammalian brain and is a major component of CSF. Immunoreactive IGFBP-2 has been identified in astrocytes, and its mRNA has been identified in fetal and adult brain and choroid plexus. The IGFBPs transport the IGFs in serum and other body fluids and appear to regulate IGF access to receptors. In vivo regulation of IGFBPs includes tissue-specific proteases, which cleave specific IGFBPs, altering their affinities for IGF peptides.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Insulin-like growth factors (IGFs): implications for aging. The insulin-like growth factors (IGF)-I and IGF-II are peptides with structural homology to insulin and potent mitogenic and anabolic actions in vitro and in vivo. IGF-I levels are growth hormone (GH)-dependent and vary strikingly with age. IGF-I levels are typically low in infancy and childhood, increase dramatically during puberty, and then gradually decline with advancing age. Whether age-associated changes in GH production or sex steroid secretion, or other unknown factors, cause diminished IGF production in the elderly remains to be determined. In the brain, IGF-II appears to be the most prevalent IGF, but a truncated form of IGF-I also has been recognized. IGF actions are mediated by binding to a family of receptors, which includes the insulin receptor, the structurally homologous type I IGF receptor, and the IGF-II/M-6P receptor, all of which are found in the central nervous system. Additionally, the IGFs bind with high affinity to a family of IGF-binding proteins (IGFBPs). Of the six known IGFBPs, IGFBP-2 appears to be the major one in the mammalian brain and is a major component of CSF. Immunoreactive IGFBP-2 has been identified in astrocytes, and its mRNA has been identified in fetal and adult brain and choroid plexus. The IGFBPs transport the IGFs in serum and other body fluids and appear to regulate IGF access to receptors. In vivo regulation of IGFBPs includes tissue-specific proteases, which cleave specific IGFBPs, altering their affinities for IGF peptides.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279738", "title": "Effect of androgens on the brain and other organs during development and aging.", "content": "Androgens have important biological effects on accessory sexual organs and have a broad range of effects on metabolic processes. Male hormones have been shown to have important organizational and activational effects on morphological, behavioral, and cognitive activity in experimental animals. Sexual dimorphic effects on cognitive and behavioral activities in animals have been linked to androgens during the fetal period. The effects of testosterone on sexual drive are well established in humans, although the threshold for such activity appears to be lower than that required for many of the other and organic effects of testosterone. There are suggestive data to link fetal androgen levels to cognitive and behavioral activities in children and adults, but the behavioral activities may be modified by social and other learning processes. Androgen levels fall in older men at a time when impaired sexual function, osteopenia, and decreased muscle mass can be identified. The relative importance of androgen deficiency in these disorders requires further study, since they are likely to be multifactorial in pathogenesis. Replacement therapy of elderly men who have lowered testosterone levels has been proposed to decrease bone and muscle loss as well as to improve sexual function and general well-being. Careful studies will be required to assess the risk-to-reward ratio of such treatment, since theoretical adverse effects on prostate and cardiovascular diseases may occur. While conservation in management has its virtues, we should be reminded that several decades ago estrogen replacement of postmenopausal women was highly criticized until data supporting its favorable therapeutic ratio were demonstrated.", "contents": "Effect of androgens on the brain and other organs during development and aging. Androgens have important biological effects on accessory sexual organs and have a broad range of effects on metabolic processes. Male hormones have been shown to have important organizational and activational effects on morphological, behavioral, and cognitive activity in experimental animals. Sexual dimorphic effects on cognitive and behavioral activities in animals have been linked to androgens during the fetal period. The effects of testosterone on sexual drive are well established in humans, although the threshold for such activity appears to be lower than that required for many of the other and organic effects of testosterone. There are suggestive data to link fetal androgen levels to cognitive and behavioral activities in children and adults, but the behavioral activities may be modified by social and other learning processes. Androgen levels fall in older men at a time when impaired sexual function, osteopenia, and decreased muscle mass can be identified. The relative importance of androgen deficiency in these disorders requires further study, since they are likely to be multifactorial in pathogenesis. Replacement therapy of elderly men who have lowered testosterone levels has been proposed to decrease bone and muscle loss as well as to improve sexual function and general well-being. Careful studies will be required to assess the risk-to-reward ratio of such treatment, since theoretical adverse effects on prostate and cardiovascular diseases may occur. While conservation in management has its virtues, we should be reminded that several decades ago estrogen replacement of postmenopausal women was highly criticized until data supporting its favorable therapeutic ratio were demonstrated."} {"id": "PMID:1279739", "title": "A simplified and rapid staining method for the HeLa x skin fibroblast human hybrid cell neoplastic transformation assay.", "content": "A simplified and rapid screening method for detecting radiation-induced neoplastically transformed foci in the HeLa x skin fibroblast human hybrid cell assay system has been developed. The method is based on the recent identification of the tumor-associated antigen in this system as intestinal alkaline phosphatase (IAP), and on the recent commercial development of a stable alkaline phosphatase chromogenic substrate solution, Western blue (WB). Cleavage of the substrate results in the production of a blue insoluble precipitate. It is shown that WB can be used on both viable and paraformaldehyde-fixed cells. Fixation does not noticeably reduce the IAP enzymatic activity. A direct comparison with the current method of immunoperoxidase (IMPO) staining indicates that the WB method is not only easier, but appears to be more sensitive in picking up weakly positive foci with a resulting higher (factor of 2.5) induced transformation frequency for 7 Gy of 137Cs gamma radiation. Whereas the IMPO staining procedure is time-consuming and requires access to large amounts of expensive IAP-specific BD6 monoclonal antibody and peroxidase-labeled secondary antibody, the WB staining procedure is rapid and utilizes an inexpensive and readily available reagent. It should now allow this assay system to enter general use.", "contents": "A simplified and rapid staining method for the HeLa x skin fibroblast human hybrid cell neoplastic transformation assay. A simplified and rapid screening method for detecting radiation-induced neoplastically transformed foci in the HeLa x skin fibroblast human hybrid cell assay system has been developed. The method is based on the recent identification of the tumor-associated antigen in this system as intestinal alkaline phosphatase (IAP), and on the recent commercial development of a stable alkaline phosphatase chromogenic substrate solution, Western blue (WB). Cleavage of the substrate results in the production of a blue insoluble precipitate. It is shown that WB can be used on both viable and paraformaldehyde-fixed cells. Fixation does not noticeably reduce the IAP enzymatic activity. A direct comparison with the current method of immunoperoxidase (IMPO) staining indicates that the WB method is not only easier, but appears to be more sensitive in picking up weakly positive foci with a resulting higher (factor of 2.5) induced transformation frequency for 7 Gy of 137Cs gamma radiation. Whereas the IMPO staining procedure is time-consuming and requires access to large amounts of expensive IAP-specific BD6 monoclonal antibody and peroxidase-labeled secondary antibody, the WB staining procedure is rapid and utilizes an inexpensive and readily available reagent. It should now allow this assay system to enter general use."} {"id": "PMID:1279740", "title": "Ectopic pregnancy: evolution after treatment with transvaginal methotrexate.", "content": "A prospective study was performed with 25 patients with ectopic pregnancies (EPs) who underwent treatment with transvaginal administration of methotrexate. Nineteen patients (76%) had positive responses to this treatment, and six (24%) had to undergo surgery: five because of increasing abdominal pain and one because of vaginal bleeding. The ultrasonographic (US) resolution of the EP was long and lagged behind the resolution at testing of levels of beta subunit of human chorionic gonadotropin (beta-hCG) in all patients. The fallopian tube in 12 (63%) of the responding group initially increased in diameter from a mean of 2.22 cm to a mean of 3.84 cm. In 13 (68%) of the responding group, it became more vascular at color Doppler examination. Eleven (92%) of the 12 EPs that increased in size also became more vascular. The increase in tubal size and vascularity, in spite of the falling beta-hCG level, represents a healing process and should cause no concern about the follow-up of these patients.", "contents": "Ectopic pregnancy: evolution after treatment with transvaginal methotrexate. A prospective study was performed with 25 patients with ectopic pregnancies (EPs) who underwent treatment with transvaginal administration of methotrexate. Nineteen patients (76%) had positive responses to this treatment, and six (24%) had to undergo surgery: five because of increasing abdominal pain and one because of vaginal bleeding. The ultrasonographic (US) resolution of the EP was long and lagged behind the resolution at testing of levels of beta subunit of human chorionic gonadotropin (beta-hCG) in all patients. The fallopian tube in 12 (63%) of the responding group initially increased in diameter from a mean of 2.22 cm to a mean of 3.84 cm. In 13 (68%) of the responding group, it became more vascular at color Doppler examination. Eleven (92%) of the 12 EPs that increased in size also became more vascular. The increase in tubal size and vascularity, in spite of the falling beta-hCG level, represents a healing process and should cause no concern about the follow-up of these patients."} {"id": "PMID:1279745", "title": "The cytoprotective properties of prostaglandin E2 against the toxic effects of actinomycin C on embryonic neural retina cells.", "content": "Prostaglandins (PGs) have been shown to cytoprotect various tissue types against the toxic effects of many chemicals. The mechanism of this protection is poorly understood, but the involvement of cAMP is often implied. Only one previous study examined nervous tissue and PG protection. The present study was designed to determine if PGE2 affords cytoprotection to a more specific nervous tissue (embryonic neural retina) from the toxicity of actinomycin C (AMC) using a trypan blue exclusion assay. The lowest concentration of PGE2 (2 x 10(-5)M) had no effect, but as the concentration increased (3 x 10(-5)M and 5 x 10(-5)M), PGE2 did afford protection against AMC in a dose dependent fashion. Theophylline treated cells were not protected, suggesting that cAMP may not be the primary mechanism of protection.", "contents": "The cytoprotective properties of prostaglandin E2 against the toxic effects of actinomycin C on embryonic neural retina cells. Prostaglandins (PGs) have been shown to cytoprotect various tissue types against the toxic effects of many chemicals. The mechanism of this protection is poorly understood, but the involvement of cAMP is often implied. Only one previous study examined nervous tissue and PG protection. The present study was designed to determine if PGE2 affords cytoprotection to a more specific nervous tissue (embryonic neural retina) from the toxicity of actinomycin C (AMC) using a trypan blue exclusion assay. The lowest concentration of PGE2 (2 x 10(-5)M) had no effect, but as the concentration increased (3 x 10(-5)M and 5 x 10(-5)M), PGE2 did afford protection against AMC in a dose dependent fashion. Theophylline treated cells were not protected, suggesting that cAMP may not be the primary mechanism of protection."} {"id": "PMID:1279746", "title": "Separation and concentration of delta 17-6-keto-PGF1 alpha using monoclonal antibody to omega 3-olefin structure of trienoic prostanoids.", "content": "A monoclonal antibody against cis-3-hexen-1-ol was prepared and used to separate and/or concentrate delta 17-6-keto-prostaglandin F1 alpha (PGF1 alpha) in the human sera. cis-3-Hexen-1-ol was conjugated with the human serum albumin (HSA) according to the N-succinimidylester method and hyperimmunized to BALB/c mouse. The monoclonal antibodies were obtained from hybridoma clones established by a fusion between SP2/0-Ag14-k13 mouse myeloma cells and splenocytes of a mouse. A monoclonal antibody, named 4G9-12B, recognized the epitope characteristic for omega 3-olefin structure. The 4G9-12B antibody became more specific for delta 17-6-keto-PGF1 alpha than 6-keto-PGF1 alpha by applying inhibition ELISA using amino-residue coating plates. Using the prepared immunoaffinity columns of this antibody, delta 17-6-keto-PGF1 alpha was clearly detected in 6 pg/ml of the human blood sera by GC/MS analysis. These results suggest that the monoclonal antibody to the partial structure of trienoic prostanoid, omega 3-olefin unit, and that its immunoaffinity columns are useful in separating and concentrating delta 17-6-keto-PGF1 alpha in the human blood or urine.", "contents": "Separation and concentration of delta 17-6-keto-PGF1 alpha using monoclonal antibody to omega 3-olefin structure of trienoic prostanoids. A monoclonal antibody against cis-3-hexen-1-ol was prepared and used to separate and/or concentrate delta 17-6-keto-prostaglandin F1 alpha (PGF1 alpha) in the human sera. cis-3-Hexen-1-ol was conjugated with the human serum albumin (HSA) according to the N-succinimidylester method and hyperimmunized to BALB/c mouse. The monoclonal antibodies were obtained from hybridoma clones established by a fusion between SP2/0-Ag14-k13 mouse myeloma cells and splenocytes of a mouse. A monoclonal antibody, named 4G9-12B, recognized the epitope characteristic for omega 3-olefin structure. The 4G9-12B antibody became more specific for delta 17-6-keto-PGF1 alpha than 6-keto-PGF1 alpha by applying inhibition ELISA using amino-residue coating plates. Using the prepared immunoaffinity columns of this antibody, delta 17-6-keto-PGF1 alpha was clearly detected in 6 pg/ml of the human blood sera by GC/MS analysis. These results suggest that the monoclonal antibody to the partial structure of trienoic prostanoid, omega 3-olefin unit, and that its immunoaffinity columns are useful in separating and concentrating delta 17-6-keto-PGF1 alpha in the human blood or urine."} {"id": "PMID:1279749", "title": "Palliation in esophageal cancer with a single session of intraluminal irradiation.", "content": "From September 1987 to December 1989, 36 patients with advanced esophageal cancer entered a study in order to determine the efficacy of palliation by a single session of intraluminal irradiation. A dose of 15 Gy was administered at 1 cm distance from the central axis of the applicator. In 22 of 32 patients alive at least 6 weeks after treatment dysphagia improved, in 14 this relief was complete. Re-obstruction occurred in 8 of the 22 responders, but a second treatment with intraluminal irradiation gave improvement in six. Intraesophageal prostheses were needed in only 6 of the 36 patients. Intraluminal irradiation is easy to administer and safe, it forms a useful addition to the therapeutic possibilities for the palliation of esophageal cancer.", "contents": "Palliation in esophageal cancer with a single session of intraluminal irradiation. From September 1987 to December 1989, 36 patients with advanced esophageal cancer entered a study in order to determine the efficacy of palliation by a single session of intraluminal irradiation. A dose of 15 Gy was administered at 1 cm distance from the central axis of the applicator. In 22 of 32 patients alive at least 6 weeks after treatment dysphagia improved, in 14 this relief was complete. Re-obstruction occurred in 8 of the 22 responders, but a second treatment with intraluminal irradiation gave improvement in six. Intraesophageal prostheses were needed in only 6 of the 36 patients. Intraluminal irradiation is easy to administer and safe, it forms a useful addition to the therapeutic possibilities for the palliation of esophageal cancer."} {"id": "PMID:1279748", "title": "Time courses of PIVKA-II and AFP levels after hepatic artery embolization and hepatic artery infusion against hepatocellular carcinoma: relation between the time course and tumor necrosis.", "content": "We examined 35 untreated patients with unresectable hepatocellular carcinoma who exhibited positivity for both plasma PIVKA-II and serum AFP, and studied the weekly course of these markers from the pre-TAE or -HAI period to the third week of treatment. We correlated changes in these markers with the tumor necrosis rate and the time course on X-ray CT images. One week after TAE, the tumor necrosis rate and the time course of PIVKA-II showed a significant correlation (r = 0.7), while the correlation was between the time course of AFP and the tumor necrosis rate was insignificant (r = 0.2). At two and three weeks after TAE, both the time course of AFP and PIVKA-II showed significant correlations with the tumor necrosis rate. In 16 patients with tumor necrosis rates of not less than 90%, the mean of the actual half-life (AHL) of PIVKA-II was 3.2 days, the shortest was 1.83 days, and 75% of all AHLs clustered from two days to four days, while the mean and shortest AHLs of AFP were six days and 2.98 days, respectively, exhibiting a broader distribution. On the other hand, in three out of the nine cases of hepatocellular carcinoma complicated with portal tumor thrombi, PIVKA-II increased after HAI in spite of a reduction in tumor size. It was suggested that the PIVKA-II level requires careful interpretation in cases of portal vein obstruction after intensive hepatic arterial infusion of anticancer agents.", "contents": "Time courses of PIVKA-II and AFP levels after hepatic artery embolization and hepatic artery infusion against hepatocellular carcinoma: relation between the time course and tumor necrosis. We examined 35 untreated patients with unresectable hepatocellular carcinoma who exhibited positivity for both plasma PIVKA-II and serum AFP, and studied the weekly course of these markers from the pre-TAE or -HAI period to the third week of treatment. We correlated changes in these markers with the tumor necrosis rate and the time course on X-ray CT images. One week after TAE, the tumor necrosis rate and the time course of PIVKA-II showed a significant correlation (r = 0.7), while the correlation was between the time course of AFP and the tumor necrosis rate was insignificant (r = 0.2). At two and three weeks after TAE, both the time course of AFP and PIVKA-II showed significant correlations with the tumor necrosis rate. In 16 patients with tumor necrosis rates of not less than 90%, the mean of the actual half-life (AHL) of PIVKA-II was 3.2 days, the shortest was 1.83 days, and 75% of all AHLs clustered from two days to four days, while the mean and shortest AHLs of AFP were six days and 2.98 days, respectively, exhibiting a broader distribution. On the other hand, in three out of the nine cases of hepatocellular carcinoma complicated with portal tumor thrombi, PIVKA-II increased after HAI in spite of a reduction in tumor size. It was suggested that the PIVKA-II level requires careful interpretation in cases of portal vein obstruction after intensive hepatic arterial infusion of anticancer agents."} {"id": "PMID:1279751", "title": "Effect of capsaicin and resiniferatoxin on peptidergic neurons in cultured dorsal root ganglion.", "content": "The neurotoxic effect of capsaicin has been shown to be selective on a subpopulation of small dorsal root ganglion neurons in newborn animals. The aim of this study was to provide evidence of the long lasting effect of capsaicin and its ultrapotent analog resiniferatoxin (RTX) on sensory peptidergic neurons maintained in organotypic cultures. The effects of the two irritants were examined on neurons that contained substance P (SP) and calcitonin gene-related peptide (CGRP). Exposure of the cultures to 10 microM capsaicin and 100 nM RTX for periods of 2 days or longer resulted in almost complete elimination of SP-immunoreactive (IR) neurites and reduction, but not elimination, of CGRP-IR neurites. In addition, both 10 microM capsaicin and 100 nM RTX significantly reduced the number of SP- and CGRP-IR cell bodies within DRG explants. Capsaicin in 100 microM concentration produced complete elimination of SP-IR fibers and a greater decrease in the number of CGRP-IR fibers, but failed to completely eliminate IR cell bodies. Exposure of the cultures to the irritants in the same concentrations for 90 min did not produce a measurable effect on SP- or CGRP-IR in neurites or cell bodies. It is important to establish that the effect of capsaicin and RTX on cultured neurons was of long duration (longer than 4 days) and is therefore different from depletion of peptides. These findings demonstrate that processes of cultured sensory neurons are much more sensitive to capsaicin and RTX than cell bodies. Furthermore, our results show that SP-IR neuronal elements are more sensitive to capsaicin than CGRP-IR elements. These data suggest that cultured sensory neurons express the functional properties of differentiated sensory neurons in vivo.", "contents": "Effect of capsaicin and resiniferatoxin on peptidergic neurons in cultured dorsal root ganglion. The neurotoxic effect of capsaicin has been shown to be selective on a subpopulation of small dorsal root ganglion neurons in newborn animals. The aim of this study was to provide evidence of the long lasting effect of capsaicin and its ultrapotent analog resiniferatoxin (RTX) on sensory peptidergic neurons maintained in organotypic cultures. The effects of the two irritants were examined on neurons that contained substance P (SP) and calcitonin gene-related peptide (CGRP). Exposure of the cultures to 10 microM capsaicin and 100 nM RTX for periods of 2 days or longer resulted in almost complete elimination of SP-immunoreactive (IR) neurites and reduction, but not elimination, of CGRP-IR neurites. In addition, both 10 microM capsaicin and 100 nM RTX significantly reduced the number of SP- and CGRP-IR cell bodies within DRG explants. Capsaicin in 100 microM concentration produced complete elimination of SP-IR fibers and a greater decrease in the number of CGRP-IR fibers, but failed to completely eliminate IR cell bodies. Exposure of the cultures to the irritants in the same concentrations for 90 min did not produce a measurable effect on SP- or CGRP-IR in neurites or cell bodies. It is important to establish that the effect of capsaicin and RTX on cultured neurons was of long duration (longer than 4 days) and is therefore different from depletion of peptides. These findings demonstrate that processes of cultured sensory neurons are much more sensitive to capsaicin and RTX than cell bodies. Furthermore, our results show that SP-IR neuronal elements are more sensitive to capsaicin than CGRP-IR elements. These data suggest that cultured sensory neurons express the functional properties of differentiated sensory neurons in vivo."} {"id": "PMID:1279752", "title": "Effects of noradrenaline and galanin on duodenal motility in the isolated perfused porcine pancreatico-duodenal block.", "content": "The influence of neurotransmitters on gastrointestinal motility is different in different segments of the gastrointestinal tract. To clarify the regulation of duodenal motility, the aim of the present study was to investigate the effects of alpha-adrenoceptor agonism and blockade and of galanin on duodenal motility. The study was undertaken in the isolated perfused porcine pancreatico-duodenal block. The agents under investigation were administered arterially. Duodenal motility was measured by means of a low-compliance perfusion system using an intraluminal catheter. In addition the concentration of galanin was measured in the portal effluent. We found that spontaneous motility was abolished by noradrenaline by an effect that was counteracted by the alpha 2-adrenoceptor antagonist idazoxan. In contrast, the selective alpha 1-adrenoceptor antagonist prazosin did not influence the effect of noradrenaline. Galanin, like noradrenaline, abolished duodenal motility. Furthermore, the concentration of galanin in the portal effluent was decreased by noradrenaline by an alpha 2-adrenoceptor mediated mechanism. We conclude that alpha 2-adrenoceptor activation and galanin inhibit duodenal motility and that the release of galanin from the pancreatico-duodenal preparation is reduced by alpha 2-adrenoceptors.", "contents": "Effects of noradrenaline and galanin on duodenal motility in the isolated perfused porcine pancreatico-duodenal block. The influence of neurotransmitters on gastrointestinal motility is different in different segments of the gastrointestinal tract. To clarify the regulation of duodenal motility, the aim of the present study was to investigate the effects of alpha-adrenoceptor agonism and blockade and of galanin on duodenal motility. The study was undertaken in the isolated perfused porcine pancreatico-duodenal block. The agents under investigation were administered arterially. Duodenal motility was measured by means of a low-compliance perfusion system using an intraluminal catheter. In addition the concentration of galanin was measured in the portal effluent. We found that spontaneous motility was abolished by noradrenaline by an effect that was counteracted by the alpha 2-adrenoceptor antagonist idazoxan. In contrast, the selective alpha 1-adrenoceptor antagonist prazosin did not influence the effect of noradrenaline. Galanin, like noradrenaline, abolished duodenal motility. Furthermore, the concentration of galanin in the portal effluent was decreased by noradrenaline by an alpha 2-adrenoceptor mediated mechanism. We conclude that alpha 2-adrenoceptor activation and galanin inhibit duodenal motility and that the release of galanin from the pancreatico-duodenal preparation is reduced by alpha 2-adrenoceptors."} {"id": "PMID:1279753", "title": "Neurokinin 1 receptors mediate substance P-induced changes in ion transport in guinea-pig ileum.", "content": "Tachykinin receptors mediating substance P-induced secretion were examined in muscle-stripped segments of guinea-pig ileum set up in flux chambers. Changes in the short-circuit current (Isc) served as an index of active, electrogenic ion transport. Substance P evoked a transient increase in Isc which was concentration-dependent. The maximal change in Isc occurred at 1 microM concentration. [Sar9,Met(O2)11]-substance P, a neurokinin 1 (NK-1) receptor agonist, evoked a similar concentration-dependent increase in Isc. [Nle10]NKA(4-10) (1 microM) or [Pro7]NKB (1 microM), selective NK2 and NK3 agonists, respectively, had minimal effects on Isc. CP-96,345 (5 microM), a nonpeptide NK-1 antagonist, and the peptide NK-1 antagonist, GR82334 (1 microM), reduced the secretory response to substance P (50 nM) in the presence and absence of tetrodotoxin (0.2 microM). The NK2 antagonist, [Tyr5,D-Trp6,8,9,Arg10]NKA(4-10) MEN 10207 had no effect on the substance P response. Tetrodotoxin (0.2 microM) significantly reduced, but did not abolish the Isc response to substance P (1 microM) and [Sar9,Met(O2)11]substance P (1 microM). The substance P response was unaltered by 5 microM atropine and 50 microM mecamylamine. Piroxicam (10 microM) or pyrilamine (10 microM) or a combination of both had no effect on the tetrodotoxin-resistant substance P response. Electrical field stimulation evoked a biphasic increase in Isc which was significantly reduced by 0.2 microM tetrodotoxin. Atropine (5 microM) reduced the first peak of the biphasic response and mecamylamine (50 microM) had no effect. Similarly, 5 microM CP-96,345 and 1 microM GR82334 did not alter the EFS-induced change Isc. The results suggest that substance P-evoked secretory responses are independent of histamine or prostaglandins. Substance P responses are mediated by an NK-1 receptor type on enteric neurons and possibly epithelial cells.", "contents": "Neurokinin 1 receptors mediate substance P-induced changes in ion transport in guinea-pig ileum. Tachykinin receptors mediating substance P-induced secretion were examined in muscle-stripped segments of guinea-pig ileum set up in flux chambers. Changes in the short-circuit current (Isc) served as an index of active, electrogenic ion transport. Substance P evoked a transient increase in Isc which was concentration-dependent. The maximal change in Isc occurred at 1 microM concentration. [Sar9,Met(O2)11]-substance P, a neurokinin 1 (NK-1) receptor agonist, evoked a similar concentration-dependent increase in Isc. [Nle10]NKA(4-10) (1 microM) or [Pro7]NKB (1 microM), selective NK2 and NK3 agonists, respectively, had minimal effects on Isc. CP-96,345 (5 microM), a nonpeptide NK-1 antagonist, and the peptide NK-1 antagonist, GR82334 (1 microM), reduced the secretory response to substance P (50 nM) in the presence and absence of tetrodotoxin (0.2 microM). The NK2 antagonist, [Tyr5,D-Trp6,8,9,Arg10]NKA(4-10) MEN 10207 had no effect on the substance P response. Tetrodotoxin (0.2 microM) significantly reduced, but did not abolish the Isc response to substance P (1 microM) and [Sar9,Met(O2)11]substance P (1 microM). The substance P response was unaltered by 5 microM atropine and 50 microM mecamylamine. Piroxicam (10 microM) or pyrilamine (10 microM) or a combination of both had no effect on the tetrodotoxin-resistant substance P response. Electrical field stimulation evoked a biphasic increase in Isc which was significantly reduced by 0.2 microM tetrodotoxin. Atropine (5 microM) reduced the first peak of the biphasic response and mecamylamine (50 microM) had no effect. Similarly, 5 microM CP-96,345 and 1 microM GR82334 did not alter the EFS-induced change Isc. The results suggest that substance P-evoked secretory responses are independent of histamine or prostaglandins. Substance P responses are mediated by an NK-1 receptor type on enteric neurons and possibly epithelial cells."} {"id": "PMID:1279754", "title": "Acute inflammation enhances substance P-induced plasma protein extravasation in the rat knee joint.", "content": "Acute inflammation of the rat knee joint was induced by intra-articular injection of 2% carrageenan. Intra-articular perfusion of the inflamed joint with substance P (SP) exacerbated the inflammatory condition as assessed by the degree of plasma protein extravasation into the synovial cavity. Protein extravasation induced by SP was enhanced and more persistent in the inflamed rat knee compared to normal animals. The time course of the response in the inflamed rat knee was related to SP concentration whilst the persistency of the response was positively correlated with the initial level of joint inflammation.", "contents": "Acute inflammation enhances substance P-induced plasma protein extravasation in the rat knee joint. Acute inflammation of the rat knee joint was induced by intra-articular injection of 2% carrageenan. Intra-articular perfusion of the inflamed joint with substance P (SP) exacerbated the inflammatory condition as assessed by the degree of plasma protein extravasation into the synovial cavity. Protein extravasation induced by SP was enhanced and more persistent in the inflamed rat knee compared to normal animals. The time course of the response in the inflamed rat knee was related to SP concentration whilst the persistency of the response was positively correlated with the initial level of joint inflammation."} {"id": "PMID:1279755", "title": "Neuropeptide Y modulates the action of vasodilator agents in guinea-pig epicardial coronary arteries.", "content": "Recently, we have demonstrated that guinea-pig epicardial coronary arteries are supplied by numerous nerve fibres containing neuropeptide Y (NPY) immunoreactivity. However, examination of vasomotor responses revealed that NPY did not elicit a contractile response in these arteries. In contrast, acetylcholine (ACh), calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP) all relaxed precontracted arteries. In the present study, we have used histochemical, immunohistochemical and in vitro pharmacological techniques, in order to further investigate the possible role of NPY in guinea-pig epicardial coronary arteries. A double-immunofluorescence staining technique revealed that CGRP and substance P were co-localized in nerve fibres distinct from those displaying NPY immunoreactivity. Furthermore, using a method combining immunofluorescence and histochemical techniques, we observed that putative cholinergic nerve fibres (identified by their acetylcholinesterase content) and NPY-immunoreactive nerve fibres are two different nerve populations. An in vitro pharmacological method demonstrated that NPY markedly inhibited the relaxant responses mediated by ACh, VIP, substance P and isoprenaline but had no effect on CGRP. These results suggest that NPY-containing nerves associated with guinea-pig epicardial coronary arteries may be predominantly involved in modulating the action of vasodilator agents.", "contents": "Neuropeptide Y modulates the action of vasodilator agents in guinea-pig epicardial coronary arteries. Recently, we have demonstrated that guinea-pig epicardial coronary arteries are supplied by numerous nerve fibres containing neuropeptide Y (NPY) immunoreactivity. However, examination of vasomotor responses revealed that NPY did not elicit a contractile response in these arteries. In contrast, acetylcholine (ACh), calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP) all relaxed precontracted arteries. In the present study, we have used histochemical, immunohistochemical and in vitro pharmacological techniques, in order to further investigate the possible role of NPY in guinea-pig epicardial coronary arteries. A double-immunofluorescence staining technique revealed that CGRP and substance P were co-localized in nerve fibres distinct from those displaying NPY immunoreactivity. Furthermore, using a method combining immunofluorescence and histochemical techniques, we observed that putative cholinergic nerve fibres (identified by their acetylcholinesterase content) and NPY-immunoreactive nerve fibres are two different nerve populations. An in vitro pharmacological method demonstrated that NPY markedly inhibited the relaxant responses mediated by ACh, VIP, substance P and isoprenaline but had no effect on CGRP. These results suggest that NPY-containing nerves associated with guinea-pig epicardial coronary arteries may be predominantly involved in modulating the action of vasodilator agents."} {"id": "PMID:1279756", "title": "Exendin-4, a new peptide from Heloderma suspectum venom, potentiates cholecystokinin-induced amylase release from rat pancreatic acini.", "content": "We examined the actions of exendin-4, a new peptide isolated from Heloderma suspectum venom, on dispersed acini from rat pancreas. Exendin-4 caused a 3-fold increase in cAMP but did not alter cellular calcium concentration. Exendin-4-induced increases in cAMP were inhibited by an exendin-receptor antagonist, exendin (9-39)NH2, but not by VIP-receptor antagonists. Whereas up to 1 microM exendin-4 alone did not alter amylase release, potentiation of enzyme release was observed when the peptide (greater than 30 pM) was combined with cholecystokinin. Potentiation of amylase release was also observed when exendin-4 was combined with carbamylcholine, bombesin or a calcium ionophore, A23187. These results indicate that stimulation of exendin receptors on rat pancreatic acini causes an increase in cellular cAMP. Although this increase in cAMP alone does not result in amylase release, combination of exendin-4 with agents that increase cell calcium results in potentiation of amylase release.", "contents": "Exendin-4, a new peptide from Heloderma suspectum venom, potentiates cholecystokinin-induced amylase release from rat pancreatic acini. We examined the actions of exendin-4, a new peptide isolated from Heloderma suspectum venom, on dispersed acini from rat pancreas. Exendin-4 caused a 3-fold increase in cAMP but did not alter cellular calcium concentration. Exendin-4-induced increases in cAMP were inhibited by an exendin-receptor antagonist, exendin (9-39)NH2, but not by VIP-receptor antagonists. Whereas up to 1 microM exendin-4 alone did not alter amylase release, potentiation of enzyme release was observed when the peptide (greater than 30 pM) was combined with cholecystokinin. Potentiation of amylase release was also observed when exendin-4 was combined with carbamylcholine, bombesin or a calcium ionophore, A23187. These results indicate that stimulation of exendin receptors on rat pancreatic acini causes an increase in cellular cAMP. Although this increase in cAMP alone does not result in amylase release, combination of exendin-4 with agents that increase cell calcium results in potentiation of amylase release."} {"id": "PMID:1279757", "title": "Dynorphin A (1-13) in the brain suppresses epinephrine-induced ventricular premature complexes and ventricular tachyarrhythmias.", "content": "The objectives of this study were to test the hypothesis that dynorphin in the central nervous system modulates epinephrine-induced cardiac arrhythmias and that central cholinergic mechanisms are operative in this action of dynorphin. Cardiac arrhythmias were produced by continuous intravenous infusion of epinephrine, in Wistar rats, previously instrumented with catheters in the lateral cerebral ventricle, femoral vein and femoral artery. Epinephrine produced ventricular premature complexes and later the development of fatal ventricular fibrillation. Dynorphin A (1-13), 5 or 20 micrograms (3 or 12 nM) administered into the lateral cerebral ventricle (ICV), significantly (P less than 0.05) increased the threshold for development of cardiac arrhythmias. Dynorphin A (1-13), 20 micrograms, increased the epinephrine dose at the occurrence of ventricular premature beats to 171 +/- 8 (mean +/- 1 S.E.M.) compared to 120 +/- 5 micrograms epinephrine/kg in the control group and increased the dose at the onset of fatal arrhythmias to 186 +/- 8 compared to 141 +/- 10 micrograms epinephrine/kg in the control group. The action of dynorphin was significantly (P less than 0.05) antagonized by the kappa opioid antagonist MR2266. Atropine sulfate, administered ICV or intravenously, produced a dose dependent antagonism of this action of dynorphin A (1-13). This was not due to the peripheral effects of atropine, as atropine methylnitrate, which does not cross the blood brain barrier, did not oppose the effects of dynorphin A (1-13). These data indicate (i) dynorphin A (1-13) increases the threshold for or suppresses the manifestations of epinephrine-induced ventricular arrhythmias, (ii) dynorphin's action on cardiac arrhythmias is mediated through central cholinergic rather than peripheral parasympathetic mechanisms (iii) dynorphin may play a role as an endogenous opioid within the brain that modulates cardiac arrhythmias in circumstances of elevated circulating epinephrine concentration.", "contents": "Dynorphin A (1-13) in the brain suppresses epinephrine-induced ventricular premature complexes and ventricular tachyarrhythmias. The objectives of this study were to test the hypothesis that dynorphin in the central nervous system modulates epinephrine-induced cardiac arrhythmias and that central cholinergic mechanisms are operative in this action of dynorphin. Cardiac arrhythmias were produced by continuous intravenous infusion of epinephrine, in Wistar rats, previously instrumented with catheters in the lateral cerebral ventricle, femoral vein and femoral artery. Epinephrine produced ventricular premature complexes and later the development of fatal ventricular fibrillation. Dynorphin A (1-13), 5 or 20 micrograms (3 or 12 nM) administered into the lateral cerebral ventricle (ICV), significantly (P less than 0.05) increased the threshold for development of cardiac arrhythmias. Dynorphin A (1-13), 20 micrograms, increased the epinephrine dose at the occurrence of ventricular premature beats to 171 +/- 8 (mean +/- 1 S.E.M.) compared to 120 +/- 5 micrograms epinephrine/kg in the control group and increased the dose at the onset of fatal arrhythmias to 186 +/- 8 compared to 141 +/- 10 micrograms epinephrine/kg in the control group. The action of dynorphin was significantly (P less than 0.05) antagonized by the kappa opioid antagonist MR2266. Atropine sulfate, administered ICV or intravenously, produced a dose dependent antagonism of this action of dynorphin A (1-13). This was not due to the peripheral effects of atropine, as atropine methylnitrate, which does not cross the blood brain barrier, did not oppose the effects of dynorphin A (1-13). These data indicate (i) dynorphin A (1-13) increases the threshold for or suppresses the manifestations of epinephrine-induced ventricular arrhythmias, (ii) dynorphin's action on cardiac arrhythmias is mediated through central cholinergic rather than peripheral parasympathetic mechanisms (iii) dynorphin may play a role as an endogenous opioid within the brain that modulates cardiac arrhythmias in circumstances of elevated circulating epinephrine concentration."} {"id": "PMID:1279758", "title": "Secretion of immunoreactive ANF from FRTL-5 rat thyroid cells: regulation by calcium ionophore A23187.", "content": "Atrial natriuretic factor-like immunoreactivity (ir-ANF) was characterized in a continuous line of rat thyroid follicular cells (FRTL-5) and the influence of the calcium ionophore A23187 on ir-ANF secretion was examined. Ir-ANF was identified by immunohistochemical staining as primarily reticular and juxtanuclear in short-term cultures, and more peripheral and granular in longer-term cultures, suggesting a process of ir-ANF packaging into secretory granules. The accumulation of ir-ANF granules was dependent upon the presence of thyrotropin (TSH) in the medium. Secreted ir-ANF was characterized using reversed-phase, high-performance liquid chromatography (RP-HPLC) and radioimmunoassay as a single peak eluting one fraction earlier than 125I-labeled rat ANF (99-126) (i.e., circulating atrial ANF) included as an internal standard. A23187 treatment of cells exhibiting primarily reticular ir-ANF caused a change to a pattern of more distinct, peripherally localized granules. This change occurred within 1 h after A23187 treatment and was dependent on the presence of Ca2+ in the medium. In cultures containing primarily ir-ANF granules, A23187 (0.5 micrograms/ml) induced a peripheral translocation of the granules at 30 min and a complete degranulation by 7 h. Enzyme-linked immunoadsorbent assay (EIA) confirmed a dose-dependent effect of A23187 on ir-ANF release into the medium. These results suggest that some of the effects of Ca2+ in the thyroid could be ascribed to its mobilization and release of ir-ANF, which in turn may have autocrine effects on thyroid follicular cells.", "contents": "Secretion of immunoreactive ANF from FRTL-5 rat thyroid cells: regulation by calcium ionophore A23187. Atrial natriuretic factor-like immunoreactivity (ir-ANF) was characterized in a continuous line of rat thyroid follicular cells (FRTL-5) and the influence of the calcium ionophore A23187 on ir-ANF secretion was examined. Ir-ANF was identified by immunohistochemical staining as primarily reticular and juxtanuclear in short-term cultures, and more peripheral and granular in longer-term cultures, suggesting a process of ir-ANF packaging into secretory granules. The accumulation of ir-ANF granules was dependent upon the presence of thyrotropin (TSH) in the medium. Secreted ir-ANF was characterized using reversed-phase, high-performance liquid chromatography (RP-HPLC) and radioimmunoassay as a single peak eluting one fraction earlier than 125I-labeled rat ANF (99-126) (i.e., circulating atrial ANF) included as an internal standard. A23187 treatment of cells exhibiting primarily reticular ir-ANF caused a change to a pattern of more distinct, peripherally localized granules. This change occurred within 1 h after A23187 treatment and was dependent on the presence of Ca2+ in the medium. In cultures containing primarily ir-ANF granules, A23187 (0.5 micrograms/ml) induced a peripheral translocation of the granules at 30 min and a complete degranulation by 7 h. Enzyme-linked immunoadsorbent assay (EIA) confirmed a dose-dependent effect of A23187 on ir-ANF release into the medium. These results suggest that some of the effects of Ca2+ in the thyroid could be ascribed to its mobilization and release of ir-ANF, which in turn may have autocrine effects on thyroid follicular cells."} {"id": "PMID:1279759", "title": "An alternative hypothesis on the role of chemically induced protein droplet (alpha 2u-globulin) nephropathy in renal carcinogenesis.", "content": "Based on associations between the accumulation of protein droplets containing alpha 2u-globulin in proximal tubular epithelial cells and increased incidences of renal tubular neoplasms in male rats, it has been suggested that the carcinogenicity of chemicals that cause alpha 2u-globulin nephropathy is unique to animals that synthesize this protein. Chemicals that caused alpha 2u-globulin nephropathy and renal carcinogenicity in male rats have not been shown to produce renal tumors in animals that lack the capability for hepatic alpha 2u-globulin synthesis, including female rats, male NBR rats, or mice of either sex. Because humans do not synthesize alpha 2u-globulin it has been suggested that chemicals which cause renal toxicity associated with alpha 2u-globulin accumulation do not pose an increased cancer risk to humans. In this review on the association between alpha 2u-globulin nephropathy and renal carcinogenesis, it is apparent that (a) there are data inconsistent with the hypothesis linking these occurrences, (b) alternative mechanisms of renal toxicity and carcinogenicity are plausible, (c) data on quantitative dose-response correspondences between the various stages of alpha 2u-globulin nephropathy and renal carcinogenicity are limited, and (d) a greater understanding of the molecular changes occurring during renal carcinogenesis is needed before assuming that the current hypothesis is correct. Future research aimed at resolving issues raised in this paper should help determine whether or not the association between alpha 2u-globulin nephropathy and renal carcinogenesis represents a cause-and-effect relationship.", "contents": "An alternative hypothesis on the role of chemically induced protein droplet (alpha 2u-globulin) nephropathy in renal carcinogenesis. Based on associations between the accumulation of protein droplets containing alpha 2u-globulin in proximal tubular epithelial cells and increased incidences of renal tubular neoplasms in male rats, it has been suggested that the carcinogenicity of chemicals that cause alpha 2u-globulin nephropathy is unique to animals that synthesize this protein. Chemicals that caused alpha 2u-globulin nephropathy and renal carcinogenicity in male rats have not been shown to produce renal tumors in animals that lack the capability for hepatic alpha 2u-globulin synthesis, including female rats, male NBR rats, or mice of either sex. Because humans do not synthesize alpha 2u-globulin it has been suggested that chemicals which cause renal toxicity associated with alpha 2u-globulin accumulation do not pose an increased cancer risk to humans. In this review on the association between alpha 2u-globulin nephropathy and renal carcinogenesis, it is apparent that (a) there are data inconsistent with the hypothesis linking these occurrences, (b) alternative mechanisms of renal toxicity and carcinogenicity are plausible, (c) data on quantitative dose-response correspondences between the various stages of alpha 2u-globulin nephropathy and renal carcinogenicity are limited, and (d) a greater understanding of the molecular changes occurring during renal carcinogenesis is needed before assuming that the current hypothesis is correct. Future research aimed at resolving issues raised in this paper should help determine whether or not the association between alpha 2u-globulin nephropathy and renal carcinogenesis represents a cause-and-effect relationship."} {"id": "PMID:1279760", "title": "[Two patients with liver cirrhosis who presented with alpha-fetoprotein values diagnostic of hepatocarcinoma but without evidence of neoplasms].", "content": "Two liver cirrhosis (LC) patients with all major risk factors for hepatocellular carcinoma (HCC) had, at presentation, serum alfa-fetoprotein levels (AFP) higher than 500 ng/ml, usually considered diagnostic for HCC. They had elevated serum ALT levels too. No neoplastic liver lesions were detected by imaging techniques in both cases. During the following three months we noted a progressive improvement of clinical conditions with contextual normalization of AFP and ALT values. Therefore we suggest, when AFP is strongly elevated in LC patients but no hepatic lesion is detectable, a check for AFP and ALT time-course, before diagnosis HCC.", "contents": "[Two patients with liver cirrhosis who presented with alpha-fetoprotein values diagnostic of hepatocarcinoma but without evidence of neoplasms]. Two liver cirrhosis (LC) patients with all major risk factors for hepatocellular carcinoma (HCC) had, at presentation, serum alfa-fetoprotein levels (AFP) higher than 500 ng/ml, usually considered diagnostic for HCC. They had elevated serum ALT levels too. No neoplastic liver lesions were detected by imaging techniques in both cases. During the following three months we noted a progressive improvement of clinical conditions with contextual normalization of AFP and ALT values. Therefore we suggest, when AFP is strongly elevated in LC patients but no hepatic lesion is detectable, a check for AFP and ALT time-course, before diagnosis HCC."} {"id": "PMID:1279761", "title": "[Efficacy and tolerability of iloprost in the treatment of digital vasculitis secondary to connective tissue diseases].", "content": "The authors have evaluated the effects of long-term treatment of digital vasculitis secondary to various types of connective tissue disease, Systemic Lupus Erythematosus (SLE), Progressive Systemic Sclerosis (PSS), Sj\u00f6gren's Syndrome (SS), using iloprost. The drug has proven to be effective both in reducing pain and clinical symptoms induced by vasospastic phenomena, as well as in promoting the healing of serious acral ischemic lesions. In the patient with LES, clinical modifications of the local vasculitic phenomena have been associated with a contemporaneous remission of the disease. The persistence of the drug's clinical effects even after suspension of treatment, instrumental and biohumoral changes and concomitant systemic effects on the disease lead to the conclusion that the drug's effect, is not merely due its vasodilating action and its ability to interfere with the coagulative process, but rather must be sought within the context of a morpho-structural repair of the microcirculation.", "contents": "[Efficacy and tolerability of iloprost in the treatment of digital vasculitis secondary to connective tissue diseases]. The authors have evaluated the effects of long-term treatment of digital vasculitis secondary to various types of connective tissue disease, Systemic Lupus Erythematosus (SLE), Progressive Systemic Sclerosis (PSS), Sj\u00f6gren's Syndrome (SS), using iloprost. The drug has proven to be effective both in reducing pain and clinical symptoms induced by vasospastic phenomena, as well as in promoting the healing of serious acral ischemic lesions. In the patient with LES, clinical modifications of the local vasculitic phenomena have been associated with a contemporaneous remission of the disease. The persistence of the drug's clinical effects even after suspension of treatment, instrumental and biohumoral changes and concomitant systemic effects on the disease lead to the conclusion that the drug's effect, is not merely due its vasodilating action and its ability to interfere with the coagulative process, but rather must be sought within the context of a morpho-structural repair of the microcirculation."} {"id": "PMID:1279762", "title": "Evaluation of methods for estimating renal medullary blood flow.", "content": "Although only 10-15% of renal blood flow enters the medulla, renal medullary hemodynamics have been implicated as a key factor for the ability of the kidney to excrete concentrated or diluted urine and to be involved in sodium homeostasis. Due to the obvious importance of medullary hemodynamics, several methods have been developed or modified for estimating regional renal blood flow. The aim of the present paper is to evaluate critically the most commonly used methods available today. Those which are considered in this paper are: (1) albumin accumulation (Lilienfield), (2) rubidium-86 uptake, (3) transit time-indicator dilution, (4) red cell velocity tracking, (5) red cell flux (fluorescently labeled red cells) and (6) laser-Doppler flowmetry. Depending on the method of choice, the reported control values for renal medullary blood flow differ up to tenfold. Overall, it appears that the discrepancies in values obtained from the different methods will not be resolved until the methods are compared directly in the same animal and during different experimental conditions. Furthermore, one needs to understand and describe accurately the involved errors so that proper corrections can be made. It seems likely, however, that the majority of the techniques can be used to study relative changes, but attempts should not be made to draw conclusions about the absolute flow value. In this regard, the laser-Doppler method seems to be superior in its simplicity of use and its large advantage of continuous and relatively noninvasive measurement.", "contents": "Evaluation of methods for estimating renal medullary blood flow. Although only 10-15% of renal blood flow enters the medulla, renal medullary hemodynamics have been implicated as a key factor for the ability of the kidney to excrete concentrated or diluted urine and to be involved in sodium homeostasis. Due to the obvious importance of medullary hemodynamics, several methods have been developed or modified for estimating regional renal blood flow. The aim of the present paper is to evaluate critically the most commonly used methods available today. Those which are considered in this paper are: (1) albumin accumulation (Lilienfield), (2) rubidium-86 uptake, (3) transit time-indicator dilution, (4) red cell velocity tracking, (5) red cell flux (fluorescently labeled red cells) and (6) laser-Doppler flowmetry. Depending on the method of choice, the reported control values for renal medullary blood flow differ up to tenfold. Overall, it appears that the discrepancies in values obtained from the different methods will not be resolved until the methods are compared directly in the same animal and during different experimental conditions. Furthermore, one needs to understand and describe accurately the involved errors so that proper corrections can be made. It seems likely, however, that the majority of the techniques can be used to study relative changes, but attempts should not be made to draw conclusions about the absolute flow value. In this regard, the laser-Doppler method seems to be superior in its simplicity of use and its large advantage of continuous and relatively noninvasive measurement."} {"id": "PMID:1279763", "title": "In vitro autoradiography reveals predominantly AT1 angiotensin II receptors in rat kidney.", "content": "Angiotensin II (Ang II) receptor subtypes in the rat kidney were investigated by using type 1 (AT1) and type 2 (AT2) Ang II receptor antagonists to discriminate specific 125I-[Sar1,Ile8] Ang II binding sites with in vitro autoradiography. DuP 753, a nonpeptide Ang II antagonist specific for the AT1 sites, potently displaced binding in glomeruli (Ki = 23.9 +/- 3.3 nM) and proximal tubules (Ki = 43.4 +/- 17 nM). By contrast, the AT2 antagonists, PD 123177 and CGP 42112A, were very weak in competing for specific 125I-[Sar1,Ile8] Ang II binding sites. AT1 receptors, as determined in the presence of an excess concentration (10 microM) of the AT2 antagonist, PD 123177, account for 95% of total renal Ang II receptors, whereas AT2 receptors, as determined in the presence of an excess concentration (10 microM) of the AT1 antagonist, DuP 753, represent approximately 5% of total renal Ang II receptors. In addition, the reducing agent, dithiothreitol, produces a dose-dependent inhibition of Ang II receptor binding with an IC50 of 2 mM, a characteristic of the AT1 receptors. These findings indicate that the AT1 receptor is the predominant subtype at multiple anatomical sites in the rat kidney.", "contents": "In vitro autoradiography reveals predominantly AT1 angiotensin II receptors in rat kidney. Angiotensin II (Ang II) receptor subtypes in the rat kidney were investigated by using type 1 (AT1) and type 2 (AT2) Ang II receptor antagonists to discriminate specific 125I-[Sar1,Ile8] Ang II binding sites with in vitro autoradiography. DuP 753, a nonpeptide Ang II antagonist specific for the AT1 sites, potently displaced binding in glomeruli (Ki = 23.9 +/- 3.3 nM) and proximal tubules (Ki = 43.4 +/- 17 nM). By contrast, the AT2 antagonists, PD 123177 and CGP 42112A, were very weak in competing for specific 125I-[Sar1,Ile8] Ang II binding sites. AT1 receptors, as determined in the presence of an excess concentration (10 microM) of the AT2 antagonist, PD 123177, account for 95% of total renal Ang II receptors, whereas AT2 receptors, as determined in the presence of an excess concentration (10 microM) of the AT1 antagonist, DuP 753, represent approximately 5% of total renal Ang II receptors. In addition, the reducing agent, dithiothreitol, produces a dose-dependent inhibition of Ang II receptor binding with an IC50 of 2 mM, a characteristic of the AT1 receptors. These findings indicate that the AT1 receptor is the predominant subtype at multiple anatomical sites in the rat kidney."} {"id": "PMID:1279764", "title": "Measurement of human active renin heterogeneity.", "content": "A method for the separation and quantitation of multiple forms of active renin in human plasma is described. Shallow gradient isoelectric focusing of plasma resolved active renin into seven distinct components in each of 10 healthy normal individuals. Plasma renin activity focused at isoelectric points of 5.71, 5.57, 5.47, 5.22, 5.08, 4.93, and 4.82 with corresponding proportions of 16.3, 15.4, 21.1, 20.3, 14.0, 10.0, and 2.5%. Silicon dioxide treatment of plasma significantly increased the yield of renin in the focusing gels. Although each individual plasma sample contained the same seven renin forms, there was variability in the relative proportions of the multiple renin forms between individuals. This variance was significantly greater than the variance introduced by the determination itself. The same seven active renin forms were also present in human renal cortical tissue. In conclusion, a method for the determination of multiple renin forms in plasma and renal cortical tissue is presented. At least seven active multiple renin forms were resolved in human plasma and renal cortex.", "contents": "Measurement of human active renin heterogeneity. A method for the separation and quantitation of multiple forms of active renin in human plasma is described. Shallow gradient isoelectric focusing of plasma resolved active renin into seven distinct components in each of 10 healthy normal individuals. Plasma renin activity focused at isoelectric points of 5.71, 5.57, 5.47, 5.22, 5.08, 4.93, and 4.82 with corresponding proportions of 16.3, 15.4, 21.1, 20.3, 14.0, 10.0, and 2.5%. Silicon dioxide treatment of plasma significantly increased the yield of renin in the focusing gels. Although each individual plasma sample contained the same seven renin forms, there was variability in the relative proportions of the multiple renin forms between individuals. This variance was significantly greater than the variance introduced by the determination itself. The same seven active renin forms were also present in human renal cortical tissue. In conclusion, a method for the determination of multiple renin forms in plasma and renal cortical tissue is presented. At least seven active multiple renin forms were resolved in human plasma and renal cortex."} {"id": "PMID:1279765", "title": "On the glomerular mechanism of the renal protein excretion. Studies in the isolated perfused rat kidney.", "content": "The glomerular permeability of the isolated perfused kidney is manifold higher than in vivo, although structural changes at the glomerular filtration barrier are not described. It has been proposed that in vivo high molecular weight plasma proteins are concentrated at the glomerular endothelium forming an additional filtration barrier ('concentration polarization'). To test this hypothesis, isolated rat kidneys were perfused with substrate-enriched Krebs-Henseleit solutions containing albumin (50 g/l) or albumin/globulin (40/10 g/l), or with plasma. The pO2 was 675 mm Hg. Furthermore, experiments were carried out with the addition of erythrocytes with and without a reduced O2 supply (pO2 35 mm Hg). Independent of the composition of the perfusate a continuously increasing glomerular permeability was observed immediately after perfusion was started. After about 10 min, a steady state value for the glomerular permeability was reached. The addition of globulin to the perfusate or perfusion with plasma did not prevent the initial increase of the permeability. However, after addition of 5% erythrocytes to the perfusate the increase of permeability was much less pronounced. Neither the reduction of the O2 supply nor the addition of erythrocytes to a higher concentration than 5% had any further effect on the glomerular permeability. These data show that concentration polarization of high molecular weight proteins does not take place at the endothelium of the glomerulus. Independent of their ability to carry O2 erythrocytes play an important role in the glomerular filtration process.", "contents": "On the glomerular mechanism of the renal protein excretion. Studies in the isolated perfused rat kidney. The glomerular permeability of the isolated perfused kidney is manifold higher than in vivo, although structural changes at the glomerular filtration barrier are not described. It has been proposed that in vivo high molecular weight plasma proteins are concentrated at the glomerular endothelium forming an additional filtration barrier ('concentration polarization'). To test this hypothesis, isolated rat kidneys were perfused with substrate-enriched Krebs-Henseleit solutions containing albumin (50 g/l) or albumin/globulin (40/10 g/l), or with plasma. The pO2 was 675 mm Hg. Furthermore, experiments were carried out with the addition of erythrocytes with and without a reduced O2 supply (pO2 35 mm Hg). Independent of the composition of the perfusate a continuously increasing glomerular permeability was observed immediately after perfusion was started. After about 10 min, a steady state value for the glomerular permeability was reached. The addition of globulin to the perfusate or perfusion with plasma did not prevent the initial increase of the permeability. However, after addition of 5% erythrocytes to the perfusate the increase of permeability was much less pronounced. Neither the reduction of the O2 supply nor the addition of erythrocytes to a higher concentration than 5% had any further effect on the glomerular permeability. These data show that concentration polarization of high molecular weight proteins does not take place at the endothelium of the glomerulus. Independent of their ability to carry O2 erythrocytes play an important role in the glomerular filtration process."} {"id": "PMID:1279766", "title": "Renal transport of endogenous amino acids. I. Comparison between immature and adult rats.", "content": "In the late neonatal period of male Wistar rats (10 days old) concentrations in plasma were higher for 5 of 24 amino acids compared to adult animals (2 months old): beta-alanine, tyrosine, glycine, histidine, and the dipeptide anserine. The plasma concentrations of tryptophan, valine and leucine were lower in young than in adult rats. The renal clearances of amino acids were lower in young rats, both in relation to 1 g b.w. and related to 1 g kidney weight. In the latter case the differences became more distinct because the relative kidney weight was higher in young than in adult animals (1.17 +/- 0.07 vs. 0.82 +/- 0.03 g/100 g b.w.) and significant age differences in renal water content did not exist. The apparently more effective tubular reabsorption capacity in young rats can be explained as follows: Because of the significantly lower GFR in 10-day-old rats compared with adults (0.46 +/- 0.03 vs. 1.10 +/- 0.09 ml/min/1 g kidney), the glomerularly filtered load of amino acids is generally lower in young rats (exceptions: tyrosine, glycine). Therefore, the amino acid transporting carrier systems are able to reabsorb the absolutely lower amounts of amino acids from the ultrafiltrate in immature animals. This hypothesis is supported if one relates the renal amino acid clearance to the clearance of inulin. In this way it is possible to show that there are absolutely no differences between both age groups indicating mature transport systems for endogenous amino acids as early as in 10-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Renal transport of endogenous amino acids. I. Comparison between immature and adult rats. In the late neonatal period of male Wistar rats (10 days old) concentrations in plasma were higher for 5 of 24 amino acids compared to adult animals (2 months old): beta-alanine, tyrosine, glycine, histidine, and the dipeptide anserine. The plasma concentrations of tryptophan, valine and leucine were lower in young than in adult rats. The renal clearances of amino acids were lower in young rats, both in relation to 1 g b.w. and related to 1 g kidney weight. In the latter case the differences became more distinct because the relative kidney weight was higher in young than in adult animals (1.17 +/- 0.07 vs. 0.82 +/- 0.03 g/100 g b.w.) and significant age differences in renal water content did not exist. The apparently more effective tubular reabsorption capacity in young rats can be explained as follows: Because of the significantly lower GFR in 10-day-old rats compared with adults (0.46 +/- 0.03 vs. 1.10 +/- 0.09 ml/min/1 g kidney), the glomerularly filtered load of amino acids is generally lower in young rats (exceptions: tyrosine, glycine). Therefore, the amino acid transporting carrier systems are able to reabsorb the absolutely lower amounts of amino acids from the ultrafiltrate in immature animals. This hypothesis is supported if one relates the renal amino acid clearance to the clearance of inulin. In this way it is possible to show that there are absolutely no differences between both age groups indicating mature transport systems for endogenous amino acids as early as in 10-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279769", "title": "Antinociceptive effect of mexiletine in diabetic mice.", "content": "We examined the effect of mexiletine on the threshold for pain perception as determined by the application of mechanical noxious stimuli (tail-pinch) in diabetic mice. Mexiletine produced a pronounced analgesic effect in diabetic mice in a dose-dependent manner. Mexiletine (10(-5)M) significantly inhibited the K(+)-evoked release of substance P from the slices of spinal cord of diabetic mice. These results suggest that the reduction of release of substance P from the nociceptive afferent terminal in the spinal cord is involved in the mechanisms of mexiletine analgesia in diabetic mice.", "contents": "Antinociceptive effect of mexiletine in diabetic mice. We examined the effect of mexiletine on the threshold for pain perception as determined by the application of mechanical noxious stimuli (tail-pinch) in diabetic mice. Mexiletine produced a pronounced analgesic effect in diabetic mice in a dose-dependent manner. Mexiletine (10(-5)M) significantly inhibited the K(+)-evoked release of substance P from the slices of spinal cord of diabetic mice. These results suggest that the reduction of release of substance P from the nociceptive afferent terminal in the spinal cord is involved in the mechanisms of mexiletine analgesia in diabetic mice."} {"id": "PMID:1279767", "title": "Renal transport of endogenous amino acids. II. Influence of treatment with triiodothyronine or dexamethasone in immature and adult rats.", "content": "Repeated administration of triiodothyronine (T3, 20 micrograms/100 g b.w., once daily for 3 days) or dexamethasone (60 micrograms/100 g b.w., once daily for 3 days) caused significant changes of amino acid plasma concentrations in young (10 days old) and adult rats (2 months old). After treatment with T3, in young animals concentrations of beta-alanine, aspartic acid, glutamic acid, ornithine, asparagine, leucine, taurine, serine, alanine, and glutamine were enhanced, whereas those of tyrosine, arginine, and threonine were significantly diminished. In adult rats only slight changes occurred after both T3 and dexamethasone. In the kidney, the reabsorbed fraction of amino acids was enhanced after both T3 and dexamethasone treatment in young rats, whereas in adult rats the two hormones were without influence on tubular reabsorption of amino acids. Taken together, both different plasma concentrations of amino acids and changes in amounts of amino acids reabsorbed in the tubuli, in adult rats the fractional excretion of amino acids was nearly unchanged following hormone treatment (exception: significant increase in taurine clearance). But in young animals the fractional excretion was reduced in 15 of 22 amino acids after dexamethasone and in 12 of 23 amino acids after T3 treatment, indicating stimulatory effects of both hormones on tubular amino acid carrier systems in immature animals.", "contents": "Renal transport of endogenous amino acids. II. Influence of treatment with triiodothyronine or dexamethasone in immature and adult rats. Repeated administration of triiodothyronine (T3, 20 micrograms/100 g b.w., once daily for 3 days) or dexamethasone (60 micrograms/100 g b.w., once daily for 3 days) caused significant changes of amino acid plasma concentrations in young (10 days old) and adult rats (2 months old). After treatment with T3, in young animals concentrations of beta-alanine, aspartic acid, glutamic acid, ornithine, asparagine, leucine, taurine, serine, alanine, and glutamine were enhanced, whereas those of tyrosine, arginine, and threonine were significantly diminished. In adult rats only slight changes occurred after both T3 and dexamethasone. In the kidney, the reabsorbed fraction of amino acids was enhanced after both T3 and dexamethasone treatment in young rats, whereas in adult rats the two hormones were without influence on tubular reabsorption of amino acids. Taken together, both different plasma concentrations of amino acids and changes in amounts of amino acids reabsorbed in the tubuli, in adult rats the fractional excretion of amino acids was nearly unchanged following hormone treatment (exception: significant increase in taurine clearance). But in young animals the fractional excretion was reduced in 15 of 22 amino acids after dexamethasone and in 12 of 23 amino acids after T3 treatment, indicating stimulatory effects of both hormones on tubular amino acid carrier systems in immature animals."} {"id": "PMID:1279770", "title": "Ill-defined choroidal neovascularization within ocular histoplasmosis scars.", "content": "Seven patients with scars typical of ocular histoplasmosis syndrome presented with new symptoms of decreased vision or metamorphopsia. In each patient the symptoms corresponded to an atrophic or \"punched-out\" histoplasmosis scar in the macula. Clinically, a small amount of subretinal fluid overlying the scars and slight hyperfluorescence were seen on fluorescein angiography. These findings were due to a choroidal neovascular membrane growing within the margins of the atrophic scar. The membranes were difficult to diagnose because of the absence of hemorrhage, pigmentation, or growth of vessels beyond the margins of the scar. Clinicians should be aware that these patients may have early and growing choroidal neovascularization and may need to undergo photocoagulation or to be followed closely.", "contents": "Ill-defined choroidal neovascularization within ocular histoplasmosis scars. Seven patients with scars typical of ocular histoplasmosis syndrome presented with new symptoms of decreased vision or metamorphopsia. In each patient the symptoms corresponded to an atrophic or \"punched-out\" histoplasmosis scar in the macula. Clinically, a small amount of subretinal fluid overlying the scars and slight hyperfluorescence were seen on fluorescein angiography. These findings were due to a choroidal neovascular membrane growing within the margins of the atrophic scar. The membranes were difficult to diagnose because of the absence of hemorrhage, pigmentation, or growth of vessels beyond the margins of the scar. Clinicians should be aware that these patients may have early and growing choroidal neovascularization and may need to undergo photocoagulation or to be followed closely."} {"id": "PMID:1279773", "title": "[Prematurity: developments during the last decade at Erasmus Hospital. II. Long-term follow-up].", "content": "Morbidity and mortality of these preterm infants weighing < 1000 g at birth was reported in another paper. The mortality and neuro-developmental prognosis improved clearly in the last 3 years. A particular attention is given for protecting these babies against brain lesions. These ELBW have a high risk of neurodevelopmental disturbances. Therefore, a multidisciplinary team follows the neurological evolution to assess the quality of neonatal care and detect and treat developmental abnormalities as early as possible. We present the weight and height evolutions, the neurological, social and familial outcome of our 15 survivors. Economical and ethical discussions are open.", "contents": "[Prematurity: developments during the last decade at Erasmus Hospital. II. Long-term follow-up]. Morbidity and mortality of these preterm infants weighing < 1000 g at birth was reported in another paper. The mortality and neuro-developmental prognosis improved clearly in the last 3 years. A particular attention is given for protecting these babies against brain lesions. These ELBW have a high risk of neurodevelopmental disturbances. Therefore, a multidisciplinary team follows the neurological evolution to assess the quality of neonatal care and detect and treat developmental abnormalities as early as possible. We present the weight and height evolutions, the neurological, social and familial outcome of our 15 survivors. Economical and ethical discussions are open."} {"id": "PMID:1279774", "title": "[Ethics versus ethos: current ethical problems in palliative oncology].", "content": "Difficult moral concerns and choices are a characteristic of palliative cancer medicine. Problems in patient information, palliative chemotherapy, treatment with unconventional remedies and clinical drug development are given as examples. The physician-scientist as member of a clinical cancer research institution particularly faces ethically troublesome situations. It is argued that next to the acquisition of bioethical competence by 'doing' staff, members working in scientific and medical frontiers should specifically be trained to identify, analyse and resolve ethical dilemmas. In conclusion, a biomedical ethics programme is presented which will be instituted at a new cancer center, comprising the establishment of a humanities research group, ethical liaison, consultation and information services as well as a system of inhouse bioethical quality control.", "contents": "[Ethics versus ethos: current ethical problems in palliative oncology]. Difficult moral concerns and choices are a characteristic of palliative cancer medicine. Problems in patient information, palliative chemotherapy, treatment with unconventional remedies and clinical drug development are given as examples. The physician-scientist as member of a clinical cancer research institution particularly faces ethically troublesome situations. It is argued that next to the acquisition of bioethical competence by 'doing' staff, members working in scientific and medical frontiers should specifically be trained to identify, analyse and resolve ethical dilemmas. In conclusion, a biomedical ethics programme is presented which will be instituted at a new cancer center, comprising the establishment of a humanities research group, ethical liaison, consultation and information services as well as a system of inhouse bioethical quality control."} {"id": "PMID:1279775", "title": "[Pathophysiology of bronchial asthma].", "content": "Until recently asthma was considered to be caused mainly by bronchospasm of the smooth airway musculature. Accordingly beta-adrenergic agonists were the drugs of choice. During the last decade, however it has become increasingly clear that ongoing chronic inflammation of the bronchial wall plays a prominent role in the disease process. During the early bronchoconstriction after allergen challenge, histamine is probably the most important mediator. The late reaction is characterized by an inflammatory infiltration of the bronchial wall, notably by eosinophils and lymphocytes. A complex interplay of mediators as leukotrienes, prostaglandins and PAF may lead to a chronic inflammation. Inflammatory changes are seen in bronchial biopsies and broncho-alveolar lavage fluid even of mild and asymptomatic asthmatic patients. Based on this new disease concept, antiinflammatory drugs have become the mainstay of therapy even in mild to moderate asthmatics. Beta-adrenergic agonists remain the most important drug for the relief of acute bronchospasm.", "contents": "[Pathophysiology of bronchial asthma]. Until recently asthma was considered to be caused mainly by bronchospasm of the smooth airway musculature. Accordingly beta-adrenergic agonists were the drugs of choice. During the last decade, however it has become increasingly clear that ongoing chronic inflammation of the bronchial wall plays a prominent role in the disease process. During the early bronchoconstriction after allergen challenge, histamine is probably the most important mediator. The late reaction is characterized by an inflammatory infiltration of the bronchial wall, notably by eosinophils and lymphocytes. A complex interplay of mediators as leukotrienes, prostaglandins and PAF may lead to a chronic inflammation. Inflammatory changes are seen in bronchial biopsies and broncho-alveolar lavage fluid even of mild and asymptomatic asthmatic patients. Based on this new disease concept, antiinflammatory drugs have become the mainstay of therapy even in mild to moderate asthmatics. Beta-adrenergic agonists remain the most important drug for the relief of acute bronchospasm."} {"id": "PMID:1279777", "title": "Elevated HbA1 due to foetal haemoglobinaemia in children. A common artifact of certain ion-exchange chromatography methods.", "content": "Foetal haemoglobin (HbF) is known to elute with glycosylated haemoglobins (HbA1) in mini-column ion-exchange chromatography, thus producing falsely elevated values for HbA1 in subjects with foetal haemoglobinaemia. We studied the occurrence of this methodological artifact in 266 patients with suspected or known insulin-dependent diabetes mellitus (IDDM) and in 205 healthy children of various age groups. HbA1 was measured using ion-exchange chromatography with prefabricated mini-columns and HbA1c and HbF by high-performance liquid chromatography (HPLC). In healthy children of over 5 years of age, the HbA1 values were usually within the reference limits for adults. However, 69% of the children younger than 1 year of age and 7% of those 1-5 years of age had HbA1 levels above 10%. Their HbA1c values were normal but the HbF values were high. Six of the 223 patients with IDDM (2.7%) and three of the 43 patients with stress glucosuria (7%) had much higher HbA1 than HbA1c values. The discrepancy was again related to the presence of raised concentrations of HbF. We conclude that foetal haemoglobinaemia is more prevalent than was previously known, especially among children younger than 5 years of age. Presence of HbF will bias the use of HbA1 as a diagnostic aid or as an index of metabolic control in children with IDDM. Methods specific for HbA1c, such as HPLC, should be used in paediatric patients.", "contents": "Elevated HbA1 due to foetal haemoglobinaemia in children. A common artifact of certain ion-exchange chromatography methods. Foetal haemoglobin (HbF) is known to elute with glycosylated haemoglobins (HbA1) in mini-column ion-exchange chromatography, thus producing falsely elevated values for HbA1 in subjects with foetal haemoglobinaemia. We studied the occurrence of this methodological artifact in 266 patients with suspected or known insulin-dependent diabetes mellitus (IDDM) and in 205 healthy children of various age groups. HbA1 was measured using ion-exchange chromatography with prefabricated mini-columns and HbA1c and HbF by high-performance liquid chromatography (HPLC). In healthy children of over 5 years of age, the HbA1 values were usually within the reference limits for adults. However, 69% of the children younger than 1 year of age and 7% of those 1-5 years of age had HbA1 levels above 10%. Their HbA1c values were normal but the HbF values were high. Six of the 223 patients with IDDM (2.7%) and three of the 43 patients with stress glucosuria (7%) had much higher HbA1 than HbA1c values. The discrepancy was again related to the presence of raised concentrations of HbF. We conclude that foetal haemoglobinaemia is more prevalent than was previously known, especially among children younger than 5 years of age. Presence of HbF will bias the use of HbA1 as a diagnostic aid or as an index of metabolic control in children with IDDM. Methods specific for HbA1c, such as HPLC, should be used in paediatric patients."} {"id": "PMID:1279778", "title": "Evidence of a stimulatory effect of cyclic AMP on pancreatic lipase and colipase synthesis in rats.", "content": "The effects of endogenous and exogenous cyclic AMP on the synthesis of pancreatic lipase, colipase, and amylase were studied. Pancreatic lobules were prepared and incubated with forskolin, dibutyryl cyclic AMP (dbcAMP), and dibutyryl cyclic GMP (dbcGMP), respectively, in the presence of 35S-cystine. The individual pancreatic enzymes were isolated by polyacrylamide gel electrophoresis, and the incorporation of radioactive cystine into lipase, colipase, and amylase was determined. Incubation with forskolin (25 microM) rapidly increased lipase synthesis rate within 30 min, followed by an increase in colipase synthesis rate after 60 min of incubation. Amylase synthesis rate did not change during the 1st h of incubation but decreased slightly when incubated for 2 h. Incubation of pancreatic lobules with dbcAMP (1 mM) for 1 h also stimulated the incorporation of cysteine into lipase and colipase by 21% and 25%, respectively, whereas incubation with dbcGMP had no effect on the synthesis rates of lipase and colipase. Neither dbcAMP nor dbcGMP had any effect on synthesis rate of amylase. It is concluded that cyclic AMP might be an important intracellular signal for the synthesis of pancreatic lipase and colipase in the rat.", "contents": "Evidence of a stimulatory effect of cyclic AMP on pancreatic lipase and colipase synthesis in rats. The effects of endogenous and exogenous cyclic AMP on the synthesis of pancreatic lipase, colipase, and amylase were studied. Pancreatic lobules were prepared and incubated with forskolin, dibutyryl cyclic AMP (dbcAMP), and dibutyryl cyclic GMP (dbcGMP), respectively, in the presence of 35S-cystine. The individual pancreatic enzymes were isolated by polyacrylamide gel electrophoresis, and the incorporation of radioactive cystine into lipase, colipase, and amylase was determined. Incubation with forskolin (25 microM) rapidly increased lipase synthesis rate within 30 min, followed by an increase in colipase synthesis rate after 60 min of incubation. Amylase synthesis rate did not change during the 1st h of incubation but decreased slightly when incubated for 2 h. Incubation of pancreatic lobules with dbcAMP (1 mM) for 1 h also stimulated the incorporation of cysteine into lipase and colipase by 21% and 25%, respectively, whereas incubation with dbcGMP had no effect on the synthesis rates of lipase and colipase. Neither dbcAMP nor dbcGMP had any effect on synthesis rate of amylase. It is concluded that cyclic AMP might be an important intracellular signal for the synthesis of pancreatic lipase and colipase in the rat."} {"id": "PMID:1279779", "title": "Biliary stenting: cosmetic or clinical value?", "content": "Since the initial description of endoscopic placement of transpapillary stents, this technique has gained wide acceptance in the management of pancreatico-biliary diseases. We now know by and large what can be achieved and what the complications are. Studies comparing endoscopic and surgical treatment in pancreatic cancer patients show an initial advantage of the endoscopic method, which is partly counterbalanced by the late complications of stent blockage. Clinical studies are necessary to define better the subgroups of patients that benefit most from the various treatment modalities. Further improvement is necessary to solve the problem of late stent occlusion.", "contents": "Biliary stenting: cosmetic or clinical value? Since the initial description of endoscopic placement of transpapillary stents, this technique has gained wide acceptance in the management of pancreatico-biliary diseases. We now know by and large what can be achieved and what the complications are. Studies comparing endoscopic and surgical treatment in pancreatic cancer patients show an initial advantage of the endoscopic method, which is partly counterbalanced by the late complications of stent blockage. Clinical studies are necessary to define better the subgroups of patients that benefit most from the various treatment modalities. Further improvement is necessary to solve the problem of late stent occlusion."} {"id": "PMID:1279776", "title": "Systemic therapy in disseminated melanoma.", "content": "There is no standard treatment for advanced melanoma. As long as metastases are satellites or in-transit metastases localized in a leg or arm, the prospects for curative treatment by isolation perfusion are good. But as soon as metastases have spread via the circulation, curative treatment with cytotoxic agents becomes virtually impossible. When the tumor burden is not too extensive, however, palliative treatment can be of clinical value. Some combinations of cytotoxic agents or combinations of biologic response modifiers have been shown to induce worthwhile remissions. Toxicity remains a problem, however. The advantages of the newer immunological approaches, especially with interleukin-2 (IL-2) and T-cell lymphocytes, is that treatment for a short period may result in good remissions at an early stage. Much clinical research is still needed to improve these costly approaches.", "contents": "Systemic therapy in disseminated melanoma. There is no standard treatment for advanced melanoma. As long as metastases are satellites or in-transit metastases localized in a leg or arm, the prospects for curative treatment by isolation perfusion are good. But as soon as metastases have spread via the circulation, curative treatment with cytotoxic agents becomes virtually impossible. When the tumor burden is not too extensive, however, palliative treatment can be of clinical value. Some combinations of cytotoxic agents or combinations of biologic response modifiers have been shown to induce worthwhile remissions. Toxicity remains a problem, however. The advantages of the newer immunological approaches, especially with interleukin-2 (IL-2) and T-cell lymphocytes, is that treatment for a short period may result in good remissions at an early stage. Much clinical research is still needed to improve these costly approaches."} {"id": "PMID:1279780", "title": "Hypothesis for the control of clotting factor VIII inhibitory antibodies by decreasing potency of helper T-cell-recognized epitopes in factor VIII.", "content": "The study of the immunobiology of FVIII inhibitors may lead to new therapies for this potentially severe complication of haemophilia A and to new principles for the use of therapeutic proteins. In order to characterize the idiotype-anti-idiotype networks regulating FVIII inhibitors, we developed rabbit anti-idiotypic sera to 7 murine inhibitors and found at least 12 independent FVIII loci to which inhibitors could be raised. Rabbit antisera to the FVIII peptide, Ser1687-Thr1695, characterized one functional site to which about 46% of patients' inhibitor sera reacted. The multiplicity of inhibitor-recognized epitopes in FVIII makes it impractical, at the present time, to develop clinically useful specific anti-idiotypic therapies for FVIII inhibitors. Alternatively, one might induce genomic mutations in recombinant FVIII molecules to decrease immunogenicity of epitopes recognized by T helper cells. Methods to design such altered therapeutic proteins are presented, based on changing the longitudinal hydrophobic strip-of-helix which is in or near many T-cell-presented epitopes.", "contents": "Hypothesis for the control of clotting factor VIII inhibitory antibodies by decreasing potency of helper T-cell-recognized epitopes in factor VIII. The study of the immunobiology of FVIII inhibitors may lead to new therapies for this potentially severe complication of haemophilia A and to new principles for the use of therapeutic proteins. In order to characterize the idiotype-anti-idiotype networks regulating FVIII inhibitors, we developed rabbit anti-idiotypic sera to 7 murine inhibitors and found at least 12 independent FVIII loci to which inhibitors could be raised. Rabbit antisera to the FVIII peptide, Ser1687-Thr1695, characterized one functional site to which about 46% of patients' inhibitor sera reacted. The multiplicity of inhibitor-recognized epitopes in FVIII makes it impractical, at the present time, to develop clinically useful specific anti-idiotypic therapies for FVIII inhibitors. Alternatively, one might induce genomic mutations in recombinant FVIII molecules to decrease immunogenicity of epitopes recognized by T helper cells. Methods to design such altered therapeutic proteins are presented, based on changing the longitudinal hydrophobic strip-of-helix which is in or near many T-cell-presented epitopes."} {"id": "PMID:1279781", "title": "Adhesion molecules involved in the interaction of LGL/NK cells and human endothelial cells stimulated with Salmonella bacteria.", "content": "Previously we showed that pretreatment of LGL/NK or HUVE cells with Salmonella bacteria augments the adhesion of LGL/NK cells to endothelium. Here we analyse the roles of HUVEC adhesion molecules VCAM-1, ICAM-1 and E-selectin, and the counter-receptors VLA-4, LFA-1 and SLex in the increase of LGL/NK adhesion to HUVEC, stimulated with Salmonella Minnesota mR595 bacteria, LPS or TNF-alpha. On Salmonella-stimulated HUVEC, VCAM-1 and ICAM-1 were the major binding structures involved, and their effect was additive in monoclonal antibody inhibition experiments. We could demonstrate the induction of both structures on cultured HUVEC after 24 h of Salmonella stimulation in flow cytometric analysis. For Salmonella-stimulated LGL/NK, the principal binding structure was LFA-1. Stimulation of LGL/NK cells did not alter the expression of the adhesion structures (subunits CD11a/CD18, CD49d/CD29), as determined by flow cytometric analysis, and thus the increased adherence is presumably produced by an increased avidity of the receptors on LGL/NK cells. Pretreatment of endothelium or lymphocytes with various stimuli, including Salmonella bacteria or LPS, leads to an activation state which provides for characteristic anchorage sites for the increased migration of LGL/NK cells towards the site of inflammation.", "contents": "Adhesion molecules involved in the interaction of LGL/NK cells and human endothelial cells stimulated with Salmonella bacteria. Previously we showed that pretreatment of LGL/NK or HUVE cells with Salmonella bacteria augments the adhesion of LGL/NK cells to endothelium. Here we analyse the roles of HUVEC adhesion molecules VCAM-1, ICAM-1 and E-selectin, and the counter-receptors VLA-4, LFA-1 and SLex in the increase of LGL/NK adhesion to HUVEC, stimulated with Salmonella Minnesota mR595 bacteria, LPS or TNF-alpha. On Salmonella-stimulated HUVEC, VCAM-1 and ICAM-1 were the major binding structures involved, and their effect was additive in monoclonal antibody inhibition experiments. We could demonstrate the induction of both structures on cultured HUVEC after 24 h of Salmonella stimulation in flow cytometric analysis. For Salmonella-stimulated LGL/NK, the principal binding structure was LFA-1. Stimulation of LGL/NK cells did not alter the expression of the adhesion structures (subunits CD11a/CD18, CD49d/CD29), as determined by flow cytometric analysis, and thus the increased adherence is presumably produced by an increased avidity of the receptors on LGL/NK cells. Pretreatment of endothelium or lymphocytes with various stimuli, including Salmonella bacteria or LPS, leads to an activation state which provides for characteristic anchorage sites for the increased migration of LGL/NK cells towards the site of inflammation."} {"id": "PMID:1279782", "title": "Human blood dendritic cells exhibit a distinct T-cell-stimulating mechanism and differentiation pattern.", "content": "In this study, the mechanisms underlying stimulation of T-cell proliferation by human blood dendritic cells (BDC) and their differentiation have been defined with a panel of monoclonal antibodies (MoAbs). It was found that the MoAbs against LFA-1 (CD11a), CD11c, LFA-3 (CD58), ICAM-1 (CD54) or HLA-DR could significantly suppress T-cell proliferation in an allogeneic mixed lymphocyte reaction (P < 0.05), while being unable to inhibit clustering of BDC with T cells. Addition of anti-CD18 or CD45 MoAbs increased the size of clusters after 18 h of culture, but had no effect on the proliferation of T cells (P < 0.05). The suppressive effect of the MoAbs may be viewed not as an inhibition of contact between BDC and T cells, but rather as a blocking of co-stimulatory signals for T-cell activation, which are mediated by interaction of the adhesion molecules. After depleting the BDC preparations of monocytes, we used a double staining in FACS analysis to demonstrate that BDC do not express specific T (CD3), B (CD20 and CD21) and myeloid cell markers (CD11b, CD13 and CD14), but abundant class II antigens. This pattern remained unaltered after 8 days of culture in the presence of 100 U/ml GM-CSF, although a threefold increase of HLA-DQ and ICAM-1 molecules on the cultured cells was observed.", "contents": "Human blood dendritic cells exhibit a distinct T-cell-stimulating mechanism and differentiation pattern. In this study, the mechanisms underlying stimulation of T-cell proliferation by human blood dendritic cells (BDC) and their differentiation have been defined with a panel of monoclonal antibodies (MoAbs). It was found that the MoAbs against LFA-1 (CD11a), CD11c, LFA-3 (CD58), ICAM-1 (CD54) or HLA-DR could significantly suppress T-cell proliferation in an allogeneic mixed lymphocyte reaction (P < 0.05), while being unable to inhibit clustering of BDC with T cells. Addition of anti-CD18 or CD45 MoAbs increased the size of clusters after 18 h of culture, but had no effect on the proliferation of T cells (P < 0.05). The suppressive effect of the MoAbs may be viewed not as an inhibition of contact between BDC and T cells, but rather as a blocking of co-stimulatory signals for T-cell activation, which are mediated by interaction of the adhesion molecules. After depleting the BDC preparations of monocytes, we used a double staining in FACS analysis to demonstrate that BDC do not express specific T (CD3), B (CD20 and CD21) and myeloid cell markers (CD11b, CD13 and CD14), but abundant class II antigens. This pattern remained unaltered after 8 days of culture in the presence of 100 U/ml GM-CSF, although a threefold increase of HLA-DQ and ICAM-1 molecules on the cultured cells was observed."} {"id": "PMID:1279783", "title": "Amino acid concentrations in plasma and skeletal muscle after transurethral resection syndrome.", "content": "The concentrations of amino acids in plasma and skeletal muscle were measured 1 and 4 hours after transurethral prostatic resection in three patients who developed symptoms of the transurethral resection syndrome. The irrigating solution contained 1.5% of glycine and 1% of ethanol. The concentrations of glycine in plasma and muscle were equal within an hour of the operation, and at four hours the abnormally high glycine concentration persisted in muscle, though it had decreased rapidly in plasma. Our data suggest that skeletal muscle is a quantitatively important reservoir for glycine when this amino acid is supplied in potentially toxic amounts, but that the plasma glycine concentration returns to normal as the patient's clinical condition improves.", "contents": "Amino acid concentrations in plasma and skeletal muscle after transurethral resection syndrome. The concentrations of amino acids in plasma and skeletal muscle were measured 1 and 4 hours after transurethral prostatic resection in three patients who developed symptoms of the transurethral resection syndrome. The irrigating solution contained 1.5% of glycine and 1% of ethanol. The concentrations of glycine in plasma and muscle were equal within an hour of the operation, and at four hours the abnormally high glycine concentration persisted in muscle, though it had decreased rapidly in plasma. Our data suggest that skeletal muscle is a quantitatively important reservoir for glycine when this amino acid is supplied in potentially toxic amounts, but that the plasma glycine concentration returns to normal as the patient's clinical condition improves."} {"id": "PMID:1279784", "title": "A comparison between two hypotonic irrigating solutions used in transurethral resections of the prostate: sorbitol (2%)-mannitol (1%) and 1.5% glycine solutions.", "content": "Two hypotonic but non-haemolysing irrigating solutions, sorbitol-mannitol (2% + 1%) and glycine (1.5%), were compared in 40 TURP cases using a continuous resection technique. Ethanol (1%) was added to the irrigating fluid as a marker to make possible early detection of fluid absorption by breath analysis. Mannitol and sorbitol were determined in plasma and urine; glycine and ethanol were determined in plasma. Apparent absorbed fluid volumes were calculated from the immediate postoperative plasma concentrations of ethanol, mannitol, sorbitol and glycine and from the elimination of mannitol in urine during 24 hours following the operation. The use of a continuous operating technique with a suprapubic trocar resulted in very small absorptions (less than 1 l) in this series. The concentrations of the two solutes in the sorbitol-mannitol irrigating fluid were balanced so that the plasma concentrations immediately postoperatively were of the same order when absorption occurred. The sorbitol concentration declined more rapidly than the mannitol concentration in conformity with previous findings. In most cases the peak plasma level was observed immediately postoperatively but in some cases at a later time (during the interval 0-2 hours), indicating absorption from a depot of fluid accumulated extravesically in addition to direct intravenous absorption. The best estimate of fluid absorption seems to be obtained from the urinary elimination of mannitol, followed by estimates based on the plasma mannitol concentration immediately postoperatively. The plasma ethanol level determined at the same time gave an estimate of the same order, whereas plasma sorbitol and glycine levels gave lower estimates (owing to rapid redistribution and metabolism).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "A comparison between two hypotonic irrigating solutions used in transurethral resections of the prostate: sorbitol (2%)-mannitol (1%) and 1.5% glycine solutions. Two hypotonic but non-haemolysing irrigating solutions, sorbitol-mannitol (2% + 1%) and glycine (1.5%), were compared in 40 TURP cases using a continuous resection technique. Ethanol (1%) was added to the irrigating fluid as a marker to make possible early detection of fluid absorption by breath analysis. Mannitol and sorbitol were determined in plasma and urine; glycine and ethanol were determined in plasma. Apparent absorbed fluid volumes were calculated from the immediate postoperative plasma concentrations of ethanol, mannitol, sorbitol and glycine and from the elimination of mannitol in urine during 24 hours following the operation. The use of a continuous operating technique with a suprapubic trocar resulted in very small absorptions (less than 1 l) in this series. The concentrations of the two solutes in the sorbitol-mannitol irrigating fluid were balanced so that the plasma concentrations immediately postoperatively were of the same order when absorption occurred. The sorbitol concentration declined more rapidly than the mannitol concentration in conformity with previous findings. In most cases the peak plasma level was observed immediately postoperatively but in some cases at a later time (during the interval 0-2 hours), indicating absorption from a depot of fluid accumulated extravesically in addition to direct intravenous absorption. The best estimate of fluid absorption seems to be obtained from the urinary elimination of mannitol, followed by estimates based on the plasma mannitol concentration immediately postoperatively. The plasma ethanol level determined at the same time gave an estimate of the same order, whereas plasma sorbitol and glycine levels gave lower estimates (owing to rapid redistribution and metabolism).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279785", "title": "Plasma protein homeostasis in chronic hemodialysis patients.", "content": "The concentrations of 25 plasma proteins were measured in 29 patients with chronic renal insufficiency. All the patients had terminal renal failure and were treated with intermittent hemodialysis, but were otherwise in good general condition at the time of investigation. The plasma levels of 8 proteins with M(r) < 50 kD were significantly elevated compared to normal subjects. In contrast, only 2/17 proteins of greater size were found in increased concentrations. The degree of increase in concentration differed substantially between individual low molecular weight proteins, suggesting a complex metabolism in addition to delayed renal elimination. Acute phase proteins and immunoglobulins were not affected by renal insufficiency per se, although erythrocyte sedimentation rates were generally high. The synthesis of acute phase proteins increased normally during the course of inflammation. We conclude that although the sedimentation rate is of no value, complicating inflammatory processes can be traced by quantitative analysis of acute phase proteins, including C-reactive protein, even in patients with severe chronic renal insufficiency.", "contents": "Plasma protein homeostasis in chronic hemodialysis patients. The concentrations of 25 plasma proteins were measured in 29 patients with chronic renal insufficiency. All the patients had terminal renal failure and were treated with intermittent hemodialysis, but were otherwise in good general condition at the time of investigation. The plasma levels of 8 proteins with M(r) < 50 kD were significantly elevated compared to normal subjects. In contrast, only 2/17 proteins of greater size were found in increased concentrations. The degree of increase in concentration differed substantially between individual low molecular weight proteins, suggesting a complex metabolism in addition to delayed renal elimination. Acute phase proteins and immunoglobulins were not affected by renal insufficiency per se, although erythrocyte sedimentation rates were generally high. The synthesis of acute phase proteins increased normally during the course of inflammation. We conclude that although the sedimentation rate is of no value, complicating inflammatory processes can be traced by quantitative analysis of acute phase proteins, including C-reactive protein, even in patients with severe chronic renal insufficiency."} {"id": "PMID:1279786", "title": "A prospective clinical five year follow up study after open synovectomy of the knee joint in patients with chronic inflammatory joint disease. The prognostic power of clinical, arthroscopic, histologic and immunohistologic variables.", "content": "Arthroscopy and clinical examination was performed on the knee joint of 26 patients with chronic inflammatory joint disease, before and at 6 and 12 months after open synovectomy. Biopsies were examined by histologic and immunohistologic methods. Clinically the patients improved until 6 months after synovectomy, and the improvement was maintained for 5 years. Patients with the best clinical function prior to synovectomy also had the best long term results (p = 0.024). The state of the cartilage was the best predicting variable with a significant prognostic power (p = 0.01). Thus patients with normal cartilage at the time of synovectomy had the best clinical score five years later. The patients with most resynovitis 12 months after surgery did less well at five year clinical follow up (p = 0.032) than those with little or no resynovitis. Absence or low number of IgA-positive plasma cells in the cellular infiltrate at 12 months after surgery correlated with a good clinical score five years after surgery (p = 0.036). This suggests that a high number of IgA-positive plasma cells may be indicative of a more aggressive, destructive disease.", "contents": "A prospective clinical five year follow up study after open synovectomy of the knee joint in patients with chronic inflammatory joint disease. The prognostic power of clinical, arthroscopic, histologic and immunohistologic variables. Arthroscopy and clinical examination was performed on the knee joint of 26 patients with chronic inflammatory joint disease, before and at 6 and 12 months after open synovectomy. Biopsies were examined by histologic and immunohistologic methods. Clinically the patients improved until 6 months after synovectomy, and the improvement was maintained for 5 years. Patients with the best clinical function prior to synovectomy also had the best long term results (p = 0.024). The state of the cartilage was the best predicting variable with a significant prognostic power (p = 0.01). Thus patients with normal cartilage at the time of synovectomy had the best clinical score five years later. The patients with most resynovitis 12 months after surgery did less well at five year clinical follow up (p = 0.032) than those with little or no resynovitis. Absence or low number of IgA-positive plasma cells in the cellular infiltrate at 12 months after surgery correlated with a good clinical score five years after surgery (p = 0.036). This suggests that a high number of IgA-positive plasma cells may be indicative of a more aggressive, destructive disease."} {"id": "PMID:1279787", "title": "Histochemical demonstration and microanalysis of possible calcium binding sites in the enamel organ of rat incisors.", "content": "The rat incisors obtained from rats perfused with high-calcium solution containing 30 to 50 mM CaCl2 were processed for rapid freeze/freeze-substitution and embedded in epoxy resin. GBHA staining, a histochemical staining for calcium, or unhydrously prepared sections revealed a large number of granular Ca-GBHA reactions in the enamel organ, most of which being located along the lateral plasma membranes of the ameloblasts. In the ameloblast layer, the reaction was negative in the presecretory stage, became intense in concert with the onset of enamel matrix formation, and remained so by the end of the transitional stage where the reaction gradually diminished. In the maturation stage, similar GBHA reactions emerged only in association with the smooth-ended ameloblasts and were absent in the ruffle-ended ameloblasts. Some granular reactions of much smaller diameter were occasionally noted in other cells of the enamel organ at both the secretory and maturation stages. Electron microscopy confirmed large electron-dense granules, each showing distinct peaks for Ca and P by microanalysis, associated with the cytoplasmic aspect of lateral plasma membranes of secretory, transitional, and smooth-ended ameloblasts. The present study thus revealed a strong calcium-binding property of the cytoplasmic aspect of lateral plasma membranes of secretory ameloblasts and its fluctuation in the maturation ameloblasts under the given experimental conditions. A necessity for an extensive analysis of membrane constituents of the enamel organ was proposed for better understanding of cellular roles in calcium regulation during amelogenesis.", "contents": "Histochemical demonstration and microanalysis of possible calcium binding sites in the enamel organ of rat incisors. The rat incisors obtained from rats perfused with high-calcium solution containing 30 to 50 mM CaCl2 were processed for rapid freeze/freeze-substitution and embedded in epoxy resin. GBHA staining, a histochemical staining for calcium, or unhydrously prepared sections revealed a large number of granular Ca-GBHA reactions in the enamel organ, most of which being located along the lateral plasma membranes of the ameloblasts. In the ameloblast layer, the reaction was negative in the presecretory stage, became intense in concert with the onset of enamel matrix formation, and remained so by the end of the transitional stage where the reaction gradually diminished. In the maturation stage, similar GBHA reactions emerged only in association with the smooth-ended ameloblasts and were absent in the ruffle-ended ameloblasts. Some granular reactions of much smaller diameter were occasionally noted in other cells of the enamel organ at both the secretory and maturation stages. Electron microscopy confirmed large electron-dense granules, each showing distinct peaks for Ca and P by microanalysis, associated with the cytoplasmic aspect of lateral plasma membranes of secretory, transitional, and smooth-ended ameloblasts. The present study thus revealed a strong calcium-binding property of the cytoplasmic aspect of lateral plasma membranes of secretory ameloblasts and its fluctuation in the maturation ameloblasts under the given experimental conditions. A necessity for an extensive analysis of membrane constituents of the enamel organ was proposed for better understanding of cellular roles in calcium regulation during amelogenesis."} {"id": "PMID:1279788", "title": "[Cardiac interactions between ketanserin and the calcium antagonist nifedipine].", "content": "Ketanserin and calcium antagonists are frequently used for the treatment of arterial hypertension in the elderly. The possibility that combined treatment with ketanserin and the calcium antagonist nifedipine have a pro-arrhythmic effect was investigated in 20 normal volunteers aged > 60 years with normal or slightly elevated blood pressure. Each subject received monotherapy with ketanserin or nifedipine for 1 week and the combined treatment during the following week. Clinical and biochemical parameters, ECG and 24-hour ECG recording were monitored before and at the end of the first and second treatment weeks. Ketanserin and nifedipine given in monotherapy or in combination did not modify, on average, blood pressure, heart rate, the biochemical variables and the QT interval. In the 24-hour ECG recordings, 2 normal subjects developed a marked increase in the frequency of ventricular ectopics, couplets and ventricular tachycardia after combined treatment. Therefore, the present investigation does not exclude the possibility that combined treatment with ketanserin and nifedipine could increase the prevalence of arrhythmia in some elderly patients.", "contents": "[Cardiac interactions between ketanserin and the calcium antagonist nifedipine]. Ketanserin and calcium antagonists are frequently used for the treatment of arterial hypertension in the elderly. The possibility that combined treatment with ketanserin and the calcium antagonist nifedipine have a pro-arrhythmic effect was investigated in 20 normal volunteers aged > 60 years with normal or slightly elevated blood pressure. Each subject received monotherapy with ketanserin or nifedipine for 1 week and the combined treatment during the following week. Clinical and biochemical parameters, ECG and 24-hour ECG recording were monitored before and at the end of the first and second treatment weeks. Ketanserin and nifedipine given in monotherapy or in combination did not modify, on average, blood pressure, heart rate, the biochemical variables and the QT interval. In the 24-hour ECG recordings, 2 normal subjects developed a marked increase in the frequency of ventricular ectopics, couplets and ventricular tachycardia after combined treatment. Therefore, the present investigation does not exclude the possibility that combined treatment with ketanserin and nifedipine could increase the prevalence of arrhythmia in some elderly patients."} {"id": "PMID:1279789", "title": "[Decreased narcissism in the aged and in suicide].", "content": "The elderly have less narcissism (= self-representation, narcissistic information, attention or libido) at their disposal to invest their own ego as well as the environment narcissistically. It therefore becomes more difficult to enlarge one's own self on encountering new persons, new environments and new customs. Some elderly may therefore feel more and more isolated and commit suicide. The rate of suicide attempts in the Canton (state) Basel-city shows a statistically significant decrease with higher age (p < 0.001) up to the age group of 60-69. Men of the age group > 80, however, manifest a significant increase in the rate of suicide attempts. The rate of fatal suicides for Swiss women increases with growing age, though not reaching statistical significance. In Basel-city, the suicide rate for women shows a rising tendency only up to the age group of 50-59 years. For Swiss men from 30-69 there is a steady, but not significant increase, which is still more pronounced from 60-69 to 70-79 (p < 0.05) and from 70-79 to > 80 (p < 0.01). For men of Basel-city the suicide rate shows, however, a clear peak in the age group 30-29 and, after a downwards trend until 40-49, an increase to a peak in the age group 60-69. From there the suicide rate stays level with a slightly decreasing trend. These statistical data seem generally to confirm, at least as a tendency, that suicide rates increase with growing age, i.e. with diminishing narcissism at one's disposal. The exception, the peak of suicides in young adults, is probably due to drug dependents who have taken their own lives. When working with elderly people, it is important to consider this reduction in narcissism and to work with them on an individual psychotherapeutic and eventually psychopharmacological but parallel also on a group basis. The individual psychotherapy should be directed toward supporting their self-confidence. In the supervision of two groups of elderlies, one of which was composed of older people who suffered from paranoid ideas, it was striking that during 75 sessions of working with this group the delusions receded and the patients became more and more communicative and no longer thought of committing suicide. In prevention it is important that the elderly be encouraged to seek participation in some group and/or family activities, though even then the individual freedom of each one not to participate in such events should be respected.", "contents": "[Decreased narcissism in the aged and in suicide]. The elderly have less narcissism (= self-representation, narcissistic information, attention or libido) at their disposal to invest their own ego as well as the environment narcissistically. It therefore becomes more difficult to enlarge one's own self on encountering new persons, new environments and new customs. Some elderly may therefore feel more and more isolated and commit suicide. The rate of suicide attempts in the Canton (state) Basel-city shows a statistically significant decrease with higher age (p < 0.001) up to the age group of 60-69. Men of the age group > 80, however, manifest a significant increase in the rate of suicide attempts. The rate of fatal suicides for Swiss women increases with growing age, though not reaching statistical significance. In Basel-city, the suicide rate for women shows a rising tendency only up to the age group of 50-59 years. For Swiss men from 30-69 there is a steady, but not significant increase, which is still more pronounced from 60-69 to 70-79 (p < 0.05) and from 70-79 to > 80 (p < 0.01). For men of Basel-city the suicide rate shows, however, a clear peak in the age group 30-29 and, after a downwards trend until 40-49, an increase to a peak in the age group 60-69. From there the suicide rate stays level with a slightly decreasing trend. These statistical data seem generally to confirm, at least as a tendency, that suicide rates increase with growing age, i.e. with diminishing narcissism at one's disposal. The exception, the peak of suicides in young adults, is probably due to drug dependents who have taken their own lives. When working with elderly people, it is important to consider this reduction in narcissism and to work with them on an individual psychotherapeutic and eventually psychopharmacological but parallel also on a group basis. The individual psychotherapy should be directed toward supporting their self-confidence. In the supervision of two groups of elderlies, one of which was composed of older people who suffered from paranoid ideas, it was striking that during 75 sessions of working with this group the delusions receded and the patients became more and more communicative and no longer thought of committing suicide. In prevention it is important that the elderly be encouraged to seek participation in some group and/or family activities, though even then the individual freedom of each one not to participate in such events should be respected."} {"id": "PMID:1279790", "title": "[A third kind of psychosis. Analysis of the literature].", "content": "Undoubtedly there exist atypical functional psychoses which differ significantly from schizophrenia and manic depressive illness. However, the atypical psychoses are conceptualized in various ways and they represent a quite heterogenous group of disorders. Regarding their main characteristics, they can be classified as 1. schizoaffective psychoses with a predominantly atypical phenomenology, 2. cycloid psychoses with a predominantly atypical course, and 3. psychogenic psychoses with a predominantly atypical etiology. For heuristic and clinical reasons it is recommendable: 1. to separate atypical psychoses from schizophrenia and manic depressive disorder and 2. to handle each of the three depicted forms of atypical psychoses as a different and independent group, regardless of possible overlaps.", "contents": "[A third kind of psychosis. Analysis of the literature]. Undoubtedly there exist atypical functional psychoses which differ significantly from schizophrenia and manic depressive illness. However, the atypical psychoses are conceptualized in various ways and they represent a quite heterogenous group of disorders. Regarding their main characteristics, they can be classified as 1. schizoaffective psychoses with a predominantly atypical phenomenology, 2. cycloid psychoses with a predominantly atypical course, and 3. psychogenic psychoses with a predominantly atypical etiology. For heuristic and clinical reasons it is recommendable: 1. to separate atypical psychoses from schizophrenia and manic depressive disorder and 2. to handle each of the three depicted forms of atypical psychoses as a different and independent group, regardless of possible overlaps."} {"id": "PMID:1279791", "title": "[Effect of diagnostic habits on the incidence of psychiatric diagnoses].", "content": "In this study, we analyzed the frequency of ICD-9-diagnoses in 2,868 inpatients (spanning 3 consecutive years) who had been admitted to the Psychiatric Hospital at the University of T\u00fcbingen. \"Paranoid schizophrenia\" (15.8%), \"endogenous monopolar depression\" (11.2%), \"alcohol dependency\" (9.9%), \"neurotic depression\" (6.5%) and \"schizoaffective psychosis\" (5.3%) turned out to be the most frequently diagnosed illnesses. The diagnosis of 6 mental illnesses described more than 50% of our patient population. In a concurrent study physicians employed at the hospital filled out a questionnaire about their diagnostic style. According to the data physicians were not aware of their narrow diagnostic style. A comparison of physicians within each ward resulted in moderate diagnostic agreement insofar as their diagnoses was based on 4-digit-ICD-categories. When using 3-digit-diagnostic main categories, diagnostic agreement appeared to be higher.", "contents": "[Effect of diagnostic habits on the incidence of psychiatric diagnoses]. In this study, we analyzed the frequency of ICD-9-diagnoses in 2,868 inpatients (spanning 3 consecutive years) who had been admitted to the Psychiatric Hospital at the University of T\u00fcbingen. \"Paranoid schizophrenia\" (15.8%), \"endogenous monopolar depression\" (11.2%), \"alcohol dependency\" (9.9%), \"neurotic depression\" (6.5%) and \"schizoaffective psychosis\" (5.3%) turned out to be the most frequently diagnosed illnesses. The diagnosis of 6 mental illnesses described more than 50% of our patient population. In a concurrent study physicians employed at the hospital filled out a questionnaire about their diagnostic style. According to the data physicians were not aware of their narrow diagnostic style. A comparison of physicians within each ward resulted in moderate diagnostic agreement insofar as their diagnoses was based on 4-digit-ICD-categories. When using 3-digit-diagnostic main categories, diagnostic agreement appeared to be higher."} {"id": "PMID:1279792", "title": "Pure sensory stroke heralding large hemispheric infarction.", "content": "A 49-year-old with long-standing hypertension and diabetes developed numbness and sensory loss over the left side of the body consistent with a diagnosis of Pure sensory stroke (PSS). However, CT showed a subcortical infarction in the middle cerebral artery (MCA) territory, which evolved a few hours later towards a large hemispheric infarction associated with severe neurologic worsening. Doppler ultrasounds showed ipsilateral carotid occlusion and contralateral severe stenosis. These findings suggest that PSS may sometimes herald large infarction in the MCA territory in association with carotid occlusion.", "contents": "Pure sensory stroke heralding large hemispheric infarction. A 49-year-old with long-standing hypertension and diabetes developed numbness and sensory loss over the left side of the body consistent with a diagnosis of Pure sensory stroke (PSS). However, CT showed a subcortical infarction in the middle cerebral artery (MCA) territory, which evolved a few hours later towards a large hemispheric infarction associated with severe neurologic worsening. Doppler ultrasounds showed ipsilateral carotid occlusion and contralateral severe stenosis. These findings suggest that PSS may sometimes herald large infarction in the MCA territory in association with carotid occlusion."} {"id": "PMID:1279793", "title": "Does chronic lung failure lead to cognitive failure?", "content": "This study seeks to find out whether impaired cognition is associated with Chronic Obstructive Pulmonary Disease (COPD). Two experiments have been carried out to address two aspects of selective attention: a focused attention paradigm with a random and a facilitated condition and a divided attention paradigm with and without interference. Twenty-eight COPD patients and 28 matched healthy controls took part in both experiments. Reaction time (RT) was the variable considered. COPD patients had slower RTs than controls, however facilitation and interference had the same effect on both groups. No correlation was found between neuropsychological measures and lung failure indices. A threshold model in the lung-failure/brain-failure trade-off is envisaged.", "contents": "Does chronic lung failure lead to cognitive failure? This study seeks to find out whether impaired cognition is associated with Chronic Obstructive Pulmonary Disease (COPD). Two experiments have been carried out to address two aspects of selective attention: a focused attention paradigm with a random and a facilitated condition and a divided attention paradigm with and without interference. Twenty-eight COPD patients and 28 matched healthy controls took part in both experiments. Reaction time (RT) was the variable considered. COPD patients had slower RTs than controls, however facilitation and interference had the same effect on both groups. No correlation was found between neuropsychological measures and lung failure indices. A threshold model in the lung-failure/brain-failure trade-off is envisaged."} {"id": "PMID:1279794", "title": "Neuropsychological evaluation of bleeding cirrhotic patients.", "content": "The cognitive profile was evaluated after an acute episode of esophageal bleeding in 26 patients with non-alcoholic hepatic cirrhosis and no previous history of acute hepatic encephalopathy. The neuropsychological test battery employed had been calibrated and standardized for age, sex, and education on a sample of 321 normal subjects. Cognitive deficits were found in some of the patients but it was not possible to selectively identify the tests that they failed or to establish a scale of severity for their scores. Further, there was no significant correlation between the psychometric and metabolic parameters. It would seem that the influence of chronic liver disease on brain functions builds up to a threshold effect, a hypothesis that calls for longitudinal studies.", "contents": "Neuropsychological evaluation of bleeding cirrhotic patients. The cognitive profile was evaluated after an acute episode of esophageal bleeding in 26 patients with non-alcoholic hepatic cirrhosis and no previous history of acute hepatic encephalopathy. The neuropsychological test battery employed had been calibrated and standardized for age, sex, and education on a sample of 321 normal subjects. Cognitive deficits were found in some of the patients but it was not possible to selectively identify the tests that they failed or to establish a scale of severity for their scores. Further, there was no significant correlation between the psychometric and metabolic parameters. It would seem that the influence of chronic liver disease on brain functions builds up to a threshold effect, a hypothesis that calls for longitudinal studies."} {"id": "PMID:1279795", "title": "[Verbal ability of Alzheimer's disease patients and very elderly control patients using the Aachen aphasia test].", "content": "We assessed language function, using the Aachen aphasia test (AAT), in 14 subjects with Alzheimer's disease and 6 control patients. Aphasia did not occur in control patients, but in 11 of 14 Alzheimer's disease patients. Impairment of object naming was the most prevalent abnormality. Performance in AAT subtests repetition, written language, object naming, comprehension and token test correlated strongly with Mini-Mental State scores.", "contents": "[Verbal ability of Alzheimer's disease patients and very elderly control patients using the Aachen aphasia test]. We assessed language function, using the Aachen aphasia test (AAT), in 14 subjects with Alzheimer's disease and 6 control patients. Aphasia did not occur in control patients, but in 11 of 14 Alzheimer's disease patients. Impairment of object naming was the most prevalent abnormality. Performance in AAT subtests repetition, written language, object naming, comprehension and token test correlated strongly with Mini-Mental State scores."} {"id": "PMID:1279796", "title": "[Multiple intracranial and spinal meningiomas].", "content": "Meningeomas are regarded as benign tumors that as a rule can be totally removed. The great prevalence of the benign types of meningeomas does not exclude their recurrence. In some cases (6-8% in the recent literature) a solitary globular tumor represents only the most visible actual growth in context of a systemic tumoral disease spreading over a wide area of arachnoid with simultaneous or delayed growth. In a series of 188 patients operated in St. Gall because of meningeomas, 13 (8%) have multiple simultaneous or delayed tumors, in one case in the spine, without neurofibromatosis. Several operations had to be performed on each patient. The prognosis quoad valetudinem is eventually worse than a solitary tumor. We present a detailed description of our cases and a r\u00e9sume of the literature.", "contents": "[Multiple intracranial and spinal meningiomas]. Meningeomas are regarded as benign tumors that as a rule can be totally removed. The great prevalence of the benign types of meningeomas does not exclude their recurrence. In some cases (6-8% in the recent literature) a solitary globular tumor represents only the most visible actual growth in context of a systemic tumoral disease spreading over a wide area of arachnoid with simultaneous or delayed growth. In a series of 188 patients operated in St. Gall because of meningeomas, 13 (8%) have multiple simultaneous or delayed tumors, in one case in the spine, without neurofibromatosis. Several operations had to be performed on each patient. The prognosis quoad valetudinem is eventually worse than a solitary tumor. We present a detailed description of our cases and a r\u00e9sume of the literature."} {"id": "PMID:1279797", "title": "Quantitative evaluation of the brain electrical activity of patients suffering from chronic obstructive bronchopneumonopathy (COBP).", "content": "The authors subjected 66 patients suffering from COBP with chronic respiratory insufficiency (22 with EGA values within standard limits, 44 with irregular PO2 and PCO2 values) to an electroencephalography with BEAM (brain electrical activity mapping). In the absence of clinically noticeable symptoms or neurologic signs of central type, more than 65% of the patients showed an increase of slow activities together with a reduction of the alpha activity presumably imputable only to the respiratory pathology.", "contents": "Quantitative evaluation of the brain electrical activity of patients suffering from chronic obstructive bronchopneumonopathy (COBP). The authors subjected 66 patients suffering from COBP with chronic respiratory insufficiency (22 with EGA values within standard limits, 44 with irregular PO2 and PCO2 values) to an electroencephalography with BEAM (brain electrical activity mapping). In the absence of clinically noticeable symptoms or neurologic signs of central type, more than 65% of the patients showed an increase of slow activities together with a reduction of the alpha activity presumably imputable only to the respiratory pathology."} {"id": "PMID:1279799", "title": "[Value of intravenous urography versus ultrasound in preoperative assessment of prostatic hyperplasia].", "content": "Even 60 years after its first clinical application intravenous urography (IVU) is still an essential part of basic diagnostic measures in benign hyperplasia of the prostate (BPH). We compared the value of the IVU to the ultrasound examination in the preoperative evaluation prospectively in 79 patients. Out of a total of 16 pathological findings (20%), only 5 findings (6.3%) could be proved in the IVU. If there was no clinical relevance, however, no treatment was necessary; neither did the pathological findings influence the strategy of surgery. Indirect signs of a tumour in 3 IVU's could be identified ultrasonically as parapelvic or cortical cysts, respectively. In addition to reliable and reproducible estimates of prostatic size, ultrasonography provides information on the residual volume, dilatation of the upper urinary tract, renal masses or stone disease. We recommend ultrasound examination as a helpful method in the preoperative evaluation of BPH. IVU should be considered only for answering specific and clinically relevant questions.", "contents": "[Value of intravenous urography versus ultrasound in preoperative assessment of prostatic hyperplasia]. Even 60 years after its first clinical application intravenous urography (IVU) is still an essential part of basic diagnostic measures in benign hyperplasia of the prostate (BPH). We compared the value of the IVU to the ultrasound examination in the preoperative evaluation prospectively in 79 patients. Out of a total of 16 pathological findings (20%), only 5 findings (6.3%) could be proved in the IVU. If there was no clinical relevance, however, no treatment was necessary; neither did the pathological findings influence the strategy of surgery. Indirect signs of a tumour in 3 IVU's could be identified ultrasonically as parapelvic or cortical cysts, respectively. In addition to reliable and reproducible estimates of prostatic size, ultrasonography provides information on the residual volume, dilatation of the upper urinary tract, renal masses or stone disease. We recommend ultrasound examination as a helpful method in the preoperative evaluation of BPH. IVU should be considered only for answering specific and clinically relevant questions."} {"id": "PMID:1279800", "title": "Trends in ambient levels of DDT and HCH residues in humans and the environment of Delhi, India.", "content": "Monitoring of DDT and HCH residues in abiotic and biotic components of the environment of Delhi during 1988 to 1989 revealed low to moderate levels of these insecticides in soil, earthworms, birds, buffalo milk, water, freshwater clams, fish, human fat, human blood and breast milk samples. Total HCH residues were less than those of DDT in all the samples. This survey indicates (in spite of the continued use of DDT and HCH in the country) a general decline in the levels of DDT residues in most of the samples studied when compared to previous surveys. Although the levels of DDT and HCH residues in fish and river water were below the permissible limits, those in human samples remained fairly high.", "contents": "Trends in ambient levels of DDT and HCH residues in humans and the environment of Delhi, India. Monitoring of DDT and HCH residues in abiotic and biotic components of the environment of Delhi during 1988 to 1989 revealed low to moderate levels of these insecticides in soil, earthworms, birds, buffalo milk, water, freshwater clams, fish, human fat, human blood and breast milk samples. Total HCH residues were less than those of DDT in all the samples. This survey indicates (in spite of the continued use of DDT and HCH in the country) a general decline in the levels of DDT residues in most of the samples studied when compared to previous surveys. Although the levels of DDT and HCH residues in fish and river water were below the permissible limits, those in human samples remained fairly high."} {"id": "PMID:1279801", "title": "Lack of protective immunity against reinfection with hepatitis C virus.", "content": "Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV.", "contents": "Lack of protective immunity against reinfection with hepatitis C virus. Some individuals infected with hepatitis C virus (HCV) experience multiple episodes of acute hepatitis. It is unclear whether these episodes are due to reinfection with HCV or to reactivation of the original virus infection. Markers of viral replication and host immunity were studied in five chimpanzees sequentially inoculated over a period of 3 years with different HCV strains of proven infectivity. Each rechallenge of a convalescent chimpanzee with the same or a different HCV strain resulted in the reappearance of viremia, which was due to infection with the subsequent challenge virus. The evidence indicates that HCV infection does not elicit protective immunity against reinfection with homologous or heterologous strains, which raises concerns for the development of effective vaccines against HCV."} {"id": "PMID:1279802", "title": "Tyrosine phosphorylation of CD22 during B cell activation.", "content": "Ligation of the antigen receptor on B cells induces the rapid phosphorylation of tyrosine on a number of cellular proteins. A monoclonal antibody that recognized a tyrosine-phosphorylated cell surface protein that was present in activated B cells was generated. Amino acid sequence analysis showed that this 140-kilodalton protein was CD22, a B cell-specific cell surface glycoprotein and putative extracellular ligand of the protein tyrosine phosphatase CD45. Tyrosine phosphorylation of CD22 may be important in B cell signal transduction, possibly through regulation of the adhesiveness of activated B cells.", "contents": "Tyrosine phosphorylation of CD22 during B cell activation. Ligation of the antigen receptor on B cells induces the rapid phosphorylation of tyrosine on a number of cellular proteins. A monoclonal antibody that recognized a tyrosine-phosphorylated cell surface protein that was present in activated B cells was generated. Amino acid sequence analysis showed that this 140-kilodalton protein was CD22, a B cell-specific cell surface glycoprotein and putative extracellular ligand of the protein tyrosine phosphatase CD45. Tyrosine phosphorylation of CD22 may be important in B cell signal transduction, possibly through regulation of the adhesiveness of activated B cells."} {"id": "PMID:1279803", "title": "Activity-dependent decrease in NMDA receptor responses during development of the visual cortex.", "content": "Plasticity of the developing visual system has been regarded as the best model for changes of neuronal connections under the influence of the environment. N-methyl-D-aspartate (NMDA) receptors are crucial for experience-dependent synaptic modifications that occur in the developing visual cortex. NMDA-mediated excitatory postsynaptic currents (EPSCs) in layer IV neurons of the visual cortex lasted longer in young rats than in adult rats, and the duration of the EPSCs became progressively shorter, in parallel with the developmental reduction in synaptic plasticity. This decrease in NMDA receptor-mediated EPSC duration is delayed when the animals are reared in the dark, a condition that prolongs developmental plasticity, and is prevented by treatment with tetrodotoxin, a procedure that inhibits neural activity. Application of L-glutamate to outside-out patches excised from layer IV neurons of young, but not of adult, rats activated prolonged bursts of NMDA channel openings. A modification of the NMDA receptor gating properties may therefore account for the age-dependent decline of visual cortical plasticity.", "contents": "Activity-dependent decrease in NMDA receptor responses during development of the visual cortex. Plasticity of the developing visual system has been regarded as the best model for changes of neuronal connections under the influence of the environment. N-methyl-D-aspartate (NMDA) receptors are crucial for experience-dependent synaptic modifications that occur in the developing visual cortex. NMDA-mediated excitatory postsynaptic currents (EPSCs) in layer IV neurons of the visual cortex lasted longer in young rats than in adult rats, and the duration of the EPSCs became progressively shorter, in parallel with the developmental reduction in synaptic plasticity. This decrease in NMDA receptor-mediated EPSC duration is delayed when the animals are reared in the dark, a condition that prolongs developmental plasticity, and is prevented by treatment with tetrodotoxin, a procedure that inhibits neural activity. Application of L-glutamate to outside-out patches excised from layer IV neurons of young, but not of adult, rats activated prolonged bursts of NMDA channel openings. A modification of the NMDA receptor gating properties may therefore account for the age-dependent decline of visual cortical plasticity."} {"id": "PMID:1279804", "title": "Transport proteins in bacteria: common themes in their design.", "content": "Bacterial transport proteins mediate passive and active transport of small solutes across membranes. Comparison of amino acid sequences shows strong conservation not only among bacterial transporters, but also between them and many transporters of animal cells; thus the study of bacterial transporters is expected to contribute to our understanding of transporters in more complex cells. During the last few years, structures of three bacterial outer membrane transporters were solved by x-ray crystallography. Much progress has also occurred in the biochemical and molecular genetic studies of transporters in the cytoplasmic membranes of bacteria, and a unifying design among membrane transporters is gradually emerging. Common structural motives and evolutionary origins among transporters with diverse energy-coupling mechanisms suggest that many transporters contain a central module forming a transmembrane channel through which the solute may pass. Energy-coupling mechanisms can be viewed as secondary features added on to these fundamental translocation units.", "contents": "Transport proteins in bacteria: common themes in their design. Bacterial transport proteins mediate passive and active transport of small solutes across membranes. Comparison of amino acid sequences shows strong conservation not only among bacterial transporters, but also between them and many transporters of animal cells; thus the study of bacterial transporters is expected to contribute to our understanding of transporters in more complex cells. During the last few years, structures of three bacterial outer membrane transporters were solved by x-ray crystallography. Much progress has also occurred in the biochemical and molecular genetic studies of transporters in the cytoplasmic membranes of bacteria, and a unifying design among membrane transporters is gradually emerging. Common structural motives and evolutionary origins among transporters with diverse energy-coupling mechanisms suggest that many transporters contain a central module forming a transmembrane channel through which the solute may pass. Energy-coupling mechanisms can be viewed as secondary features added on to these fundamental translocation units."} {"id": "PMID:1279805", "title": "Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein.", "content": "Fibronectin type III domains are found in many different proteins including cell surface receptors and cell adhesion molecules. The crystal structure of one such domain from the extracellular matrix protein tenascin was determined. The structure was solved by multiwavelength anomalous diffraction (MAD) phasing of the selenomethionyl protein and has been refined to 1.8 angstrom resolution. The folding topology of this domain is identical to that of the extracellular domains of the human growth hormone receptor, the second domain of CD4, and PapD. Although distinct, this topology is similar to that of immunoglobulin constant domains. An Arg-Gly-Asp (RGD) sequence that can function for cell adhesion is found in a tight turn on an exposed loop.", "contents": "Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein. Fibronectin type III domains are found in many different proteins including cell surface receptors and cell adhesion molecules. The crystal structure of one such domain from the extracellular matrix protein tenascin was determined. The structure was solved by multiwavelength anomalous diffraction (MAD) phasing of the selenomethionyl protein and has been refined to 1.8 angstrom resolution. The folding topology of this domain is identical to that of the extracellular domains of the human growth hormone receptor, the second domain of CD4, and PapD. Although distinct, this topology is similar to that of immunoglobulin constant domains. An Arg-Gly-Asp (RGD) sequence that can function for cell adhesion is found in a tight turn on an exposed loop."} {"id": "PMID:1279806", "title": "Mechanism of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase.", "content": "Two DNA strand transfer reactions occur during retroviral reverse transcription. The mechanism of the first, minus strand strong-stop DNA, transfer has been studied in vitro with human immunodeficiency virus 1 reverse transcriptase (HIV-1 RT) and a model template-primer system derived from the HIV-1 genome. The results reveal that HIV-1 RT alone can catalyze DNA strand transfer reactions. Two kinetically distinct ribonuclease (RNase) H activities associated with HIV-1 RT are required for removal of RNA fragments annealed to the nascent DNA strand. Examination of the binding of DNA.RNA duplex and single-stranded RNA to HIV-1 RT during strand transfer supports a model where the enzyme accommodates both the acceptor RNA template and the nascent DNA strand before the transfer event is completed. The polymerase activity incorporated additional bases beyond the 5' end of the RNA template, resulting in a base misincorporation upon DNA strand transfer. Such a process occurring in vivo during retroviral homologous recombination could contribute to the hypermutability of the HIV-1 genome.", "contents": "Mechanism of DNA strand transfer reactions catalyzed by HIV-1 reverse transcriptase. Two DNA strand transfer reactions occur during retroviral reverse transcription. The mechanism of the first, minus strand strong-stop DNA, transfer has been studied in vitro with human immunodeficiency virus 1 reverse transcriptase (HIV-1 RT) and a model template-primer system derived from the HIV-1 genome. The results reveal that HIV-1 RT alone can catalyze DNA strand transfer reactions. Two kinetically distinct ribonuclease (RNase) H activities associated with HIV-1 RT are required for removal of RNA fragments annealed to the nascent DNA strand. Examination of the binding of DNA.RNA duplex and single-stranded RNA to HIV-1 RT during strand transfer supports a model where the enzyme accommodates both the acceptor RNA template and the nascent DNA strand before the transfer event is completed. The polymerase activity incorporated additional bases beyond the 5' end of the RNA template, resulting in a base misincorporation upon DNA strand transfer. Such a process occurring in vivo during retroviral homologous recombination could contribute to the hypermutability of the HIV-1 genome."} {"id": "PMID:1279807", "title": "A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels.", "content": "The overall sequence similarity between the voltage-activated K+ channels and cyclic nucleotide-gated ion channels from retinal and olfactory neurons suggests that they arose from a common ancestor. On the basis of sequence comparisons, mutations were introduced into the pore of a voltage-activated K+ channel. These mutations confer the essential features of ion conduction in the cyclic nucleotide-gated ion channels; the mutant K+ channels display little selectivity among monovalent cations and are blocked by divalent cations. The property of K+ selectivity is related to the presence of two amino acids that are absent from the pore-forming region of the cyclic nucleotide-gated channels. These data demonstrate that very small differences in the primary structure of an ion channel can account for extreme functional diversity, and they suggest a possible connection between the pore-forming regions of K+, Ca2+, and cyclic nucleotide-gated ion channels.", "contents": "A functional connection between the pores of distantly related ion channels as revealed by mutant K+ channels. The overall sequence similarity between the voltage-activated K+ channels and cyclic nucleotide-gated ion channels from retinal and olfactory neurons suggests that they arose from a common ancestor. On the basis of sequence comparisons, mutations were introduced into the pore of a voltage-activated K+ channel. These mutations confer the essential features of ion conduction in the cyclic nucleotide-gated ion channels; the mutant K+ channels display little selectivity among monovalent cations and are blocked by divalent cations. The property of K+ selectivity is related to the presence of two amino acids that are absent from the pore-forming region of the cyclic nucleotide-gated channels. These data demonstrate that very small differences in the primary structure of an ion channel can account for extreme functional diversity, and they suggest a possible connection between the pore-forming regions of K+, Ca2+, and cyclic nucleotide-gated ion channels."} {"id": "PMID:1279808", "title": "Stability and properties of double and triple helices: dramatic effects of RNA or DNA backbone composition.", "content": "Studies of a series of short oligonucleotide double and triple helices containing either all RNA, all DNA, or a mixture of the two show strand-dependent variation in their stability and structure. The variation in stability for both groups falls over a range of greater than 10 kilocalories per mole. In forming the triple helix, RNA is favored on both pyrimidine strands, whereas DNA is favored on the purine strand. In general, relatively unstable duplexes form particularly stable triplexes and vice versa. Structural data indicate that the strands in hybrid helices adopt a conformation that is intermediate between molecules containing all DNA and all RNA. Thus, RNA-DNA hybrids were not forced into the conformation of the RNA (A-form). The provocative stability of the triplex with an RNA third strand+DNA duplex points to novel antisense strategies and opens the possibility of an in vivo role of these structures. Overall, the data emphasize the fundamental role of sugars in determining the properties of nucleic acid complexes.", "contents": "Stability and properties of double and triple helices: dramatic effects of RNA or DNA backbone composition. Studies of a series of short oligonucleotide double and triple helices containing either all RNA, all DNA, or a mixture of the two show strand-dependent variation in their stability and structure. The variation in stability for both groups falls over a range of greater than 10 kilocalories per mole. In forming the triple helix, RNA is favored on both pyrimidine strands, whereas DNA is favored on the purine strand. In general, relatively unstable duplexes form particularly stable triplexes and vice versa. Structural data indicate that the strands in hybrid helices adopt a conformation that is intermediate between molecules containing all DNA and all RNA. Thus, RNA-DNA hybrids were not forced into the conformation of the RNA (A-form). The provocative stability of the triplex with an RNA third strand+DNA duplex points to novel antisense strategies and opens the possibility of an in vivo role of these structures. Overall, the data emphasize the fundamental role of sugars in determining the properties of nucleic acid complexes."} {"id": "PMID:1279809", "title": "A multifunctional aqueous channel formed by CFTR.", "content": "The cystic fibrosis gene product (CFTR) is a complex protein that functions as an adenosine 3,5-monophosphate (cAMP)-stimulated ion channel and possibly as a regulator of intracellular processes. In order to determine whether the CFTR molecule contains a functional aqueous pathway, anion, water, and urea transport were measured in Xenopus oocytes expressing CFTR. Cyclic AMP agonists induced a Cl- conductance of 94 microsiemens and an increase in water permeability of 4 x 10(-4) centimeter per second that was inhibited by a Cl- channel blocker and was dependent on anion composition. CFTR has a calculated single channel water conductance of 9 x 10(-13) cubic centimeter per second, suggesting a pore-like aqueous pathway. Oocytes expressing CFTR also showed cAMP-stimulated transport of urea but not the larger solute sucrose. Thus CFTR contains a cAMP-stimulated aqueous pore that can transport anions, water, and small solutes. The results also provide functional evidence for water movement through an ion channel.", "contents": "A multifunctional aqueous channel formed by CFTR. The cystic fibrosis gene product (CFTR) is a complex protein that functions as an adenosine 3,5-monophosphate (cAMP)-stimulated ion channel and possibly as a regulator of intracellular processes. In order to determine whether the CFTR molecule contains a functional aqueous pathway, anion, water, and urea transport were measured in Xenopus oocytes expressing CFTR. Cyclic AMP agonists induced a Cl- conductance of 94 microsiemens and an increase in water permeability of 4 x 10(-4) centimeter per second that was inhibited by a Cl- channel blocker and was dependent on anion composition. CFTR has a calculated single channel water conductance of 9 x 10(-13) cubic centimeter per second, suggesting a pore-like aqueous pathway. Oocytes expressing CFTR also showed cAMP-stimulated transport of urea but not the larger solute sucrose. Thus CFTR contains a cAMP-stimulated aqueous pore that can transport anions, water, and small solutes. The results also provide functional evidence for water movement through an ion channel."} {"id": "PMID:1279810", "title": "Porins in the cell wall of mycobacteria.", "content": "The cell wall of mycobacteria is an efficient permeability barrier that makes mycobacteria naturally resistant to most antibiotics. Liposome swelling assays and planar bilayer experiments were used to investigate the diffusion process of hydrophilic molecules through the cell wall of Mycobacterium chelonae and identify the main hydrophilic pathway. A 59-kilodalton cell wall protein formed a water-filled channel with a diameter of 2.2 nanometers and an average single-channel conductance equal to 2.7 nanosiemens in 1 M potassium chloride. These results suggest that porins can be found in the cell wall of a Gram-positive bacterium. A better knowledge of the hydrophilic pathways should help in the design of more effective antimycobacterial agents.", "contents": "Porins in the cell wall of mycobacteria. The cell wall of mycobacteria is an efficient permeability barrier that makes mycobacteria naturally resistant to most antibiotics. Liposome swelling assays and planar bilayer experiments were used to investigate the diffusion process of hydrophilic molecules through the cell wall of Mycobacterium chelonae and identify the main hydrophilic pathway. A 59-kilodalton cell wall protein formed a water-filled channel with a diameter of 2.2 nanometers and an average single-channel conductance equal to 2.7 nanosiemens in 1 M potassium chloride. These results suggest that porins can be found in the cell wall of a Gram-positive bacterium. A better knowledge of the hydrophilic pathways should help in the design of more effective antimycobacterial agents."} {"id": "PMID:1279811", "title": "Antisense and antigene properties of peptide nucleic acids.", "content": "Peptide nucleic acids (PNAs) are polyamide oligomers that can strand invade duplex DNA, causing displacement of one DNA strand and formation of a D-loop. Binding of either a T10 PNA or a mixed sequence 15-mer PNA to the transcribed strand of a G-free transcription cassette caused 90 to 100 percent site-specific termination of pol II transcription elongation. When a T10 PNA was bound on the nontranscribed strand, site-specific inhibition never exceeded 50 percent. Binding of PNAs to RNA resulted in site-specific termination of both reverse transcription and in vitro translation, precisely at the position of the PNA.RNA heteroduplex. Nuclear microinjection of cells constitutively expressing SV40 large T antigen (T Ag) with either a 15-mer or 20-mer PNA targeted to the T Ag messenger RNA suppressed T Ag expression. This effect was specific in that there was no reduction in beta-galactosidase expression from a coinjected expression vector and no inhibition of T Ag expression after microinjection of a 10-mer PNA.", "contents": "Antisense and antigene properties of peptide nucleic acids. Peptide nucleic acids (PNAs) are polyamide oligomers that can strand invade duplex DNA, causing displacement of one DNA strand and formation of a D-loop. Binding of either a T10 PNA or a mixed sequence 15-mer PNA to the transcribed strand of a G-free transcription cassette caused 90 to 100 percent site-specific termination of pol II transcription elongation. When a T10 PNA was bound on the nontranscribed strand, site-specific inhibition never exceeded 50 percent. Binding of PNAs to RNA resulted in site-specific termination of both reverse transcription and in vitro translation, precisely at the position of the PNA.RNA heteroduplex. Nuclear microinjection of cells constitutively expressing SV40 large T antigen (T Ag) with either a 15-mer or 20-mer PNA targeted to the T Ag messenger RNA suppressed T Ag expression. This effect was specific in that there was no reduction in beta-galactosidase expression from a coinjected expression vector and no inhibition of T Ag expression after microinjection of a 10-mer PNA."} {"id": "PMID:1279812", "title": "Amelioration of autoimmune encephalomyelitis by myelin basic protein synthetic peptide-induced anergy.", "content": "Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the central nervous system that can be induced in susceptible strains of mice by immunization with myelin basic protein (MBP) or its immunodominant T cell determinants, serves as a model of human multiple sclerosis. Tolerance to MBP in adult mice was induced by intraperitoneal injection of synthetic peptides of immunodominant determinants of MBP and prevented MBP-induced EAE. Furthermore, tolerance-inducing regimens of peptides administered to mice after the disease had begun (10 days after induction with MBP) blocked the progression and decreased the severity of EAE. Peptide-induced tolerance resulted from the induction of anergy in proliferative, antigen-specific T cells.", "contents": "Amelioration of autoimmune encephalomyelitis by myelin basic protein synthetic peptide-induced anergy. Experimental autoimmune encephalomyelitis (EAE), a demyelinating disease of the central nervous system that can be induced in susceptible strains of mice by immunization with myelin basic protein (MBP) or its immunodominant T cell determinants, serves as a model of human multiple sclerosis. Tolerance to MBP in adult mice was induced by intraperitoneal injection of synthetic peptides of immunodominant determinants of MBP and prevented MBP-induced EAE. Furthermore, tolerance-inducing regimens of peptides administered to mice after the disease had begun (10 days after induction with MBP) blocked the progression and decreased the severity of EAE. Peptide-induced tolerance resulted from the induction of anergy in proliferative, antigen-specific T cells."} {"id": "PMID:1279813", "title": "Intrinsic quantal variability due to stochastic properties of receptor-transmitter interactions.", "content": "Synaptic events at the neuromuscular junction are integer multiples of a quantum, the postsynaptic response to transmitter released from one presynaptic vesicle. At central synapses where quanta are small, it has been suggested they are invariant due to occupation of all postsynaptic receptors, a concept neglecting inherent fluctuations in channel behavior. If this did occur, the quantal release model would not apply there and could not be used to localize sites of synaptic modification. Monte Carlo simulations of quanta include transmitter diffusion and interactions with postsynaptic receptors that are treated probabilistically. These models suggest that when there are few postsynaptic channels available at a synapse, their stochastic behavior produces significant intrinsic variance in response amplitude and kinetics, and saturation does not occur. These results were confirmed by analysis of inhibitory quanta in embryonic and adult Mauthner cells involving a small and large number of channels, respectively. The findings apply to excitatory synapses as well.", "contents": "Intrinsic quantal variability due to stochastic properties of receptor-transmitter interactions. Synaptic events at the neuromuscular junction are integer multiples of a quantum, the postsynaptic response to transmitter released from one presynaptic vesicle. At central synapses where quanta are small, it has been suggested they are invariant due to occupation of all postsynaptic receptors, a concept neglecting inherent fluctuations in channel behavior. If this did occur, the quantal release model would not apply there and could not be used to localize sites of synaptic modification. Monte Carlo simulations of quanta include transmitter diffusion and interactions with postsynaptic receptors that are treated probabilistically. These models suggest that when there are few postsynaptic channels available at a synapse, their stochastic behavior produces significant intrinsic variance in response amplitude and kinetics, and saturation does not occur. These results were confirmed by analysis of inhibitory quanta in embryonic and adult Mauthner cells involving a small and large number of channels, respectively. The findings apply to excitatory synapses as well."} {"id": "PMID:1279815", "title": "Surgical treatment of metastatic spine disease.", "content": "The results of surgical intervention for metastatic disease on 56 consecutive patients since 1980 were reviewed. Two patients underwent a second procedure to stabilize remote levels of spinal involvement, for a total of 58 surgeries. All 56 patients presented with pain. After surgery, significant relief was noted by 51 (91%). Twenty-seven patients presented with neurologic compromise. After operation, neurologic improvement was noted in 20 (74%). No patient's neurologic function deteriorated secondary to surgical intervention. Twenty-one patients were bedridden before surgery secondary to pain or paresis. After operation, improvement in activity level was achieved in 16 (76%) of these patients. In summary, the goal of surgical treatment of metastatic spine disease is to improve the quality of the remaining life, by the relief of pain and preservation or restoration of neurologic function. The dismal consequences of prolonged bed rest, paraplegia, and a painful premature demise can be avoided with thoughtful and timely surgical intervention.", "contents": "Surgical treatment of metastatic spine disease. The results of surgical intervention for metastatic disease on 56 consecutive patients since 1980 were reviewed. Two patients underwent a second procedure to stabilize remote levels of spinal involvement, for a total of 58 surgeries. All 56 patients presented with pain. After surgery, significant relief was noted by 51 (91%). Twenty-seven patients presented with neurologic compromise. After operation, neurologic improvement was noted in 20 (74%). No patient's neurologic function deteriorated secondary to surgical intervention. Twenty-one patients were bedridden before surgery secondary to pain or paresis. After operation, improvement in activity level was achieved in 16 (76%) of these patients. In summary, the goal of surgical treatment of metastatic spine disease is to improve the quality of the remaining life, by the relief of pain and preservation or restoration of neurologic function. The dismal consequences of prolonged bed rest, paraplegia, and a painful premature demise can be avoided with thoughtful and timely surgical intervention."} {"id": "PMID:1279816", "title": "Age-related phenomena in the lumbar intervertebral discs. Lipofuscin and amyloid deposition.", "content": "In 69 lumbar intervertebral discs from 69 autopsies, lipofuscin was seen in discs from individuals older than 50 years of age and amyloids in the discs of individuals older than 40 years of age. In 261 intervertebral disc tissue specimens collected at the time of surgery for disc herniation, lipofuscin was seen in the discs of individuals older than 20 years of age and amyloids in the discs of individuals older than 15 years of age. It is speculated that amyloids and lipofuscin are a sign of aging in the intervertebral disc as in other tissues. Furthermore, amyloids and lipofuscin were seen in the operated discs of young individuals than in the autopsy cases.", "contents": "Age-related phenomena in the lumbar intervertebral discs. Lipofuscin and amyloid deposition. In 69 lumbar intervertebral discs from 69 autopsies, lipofuscin was seen in discs from individuals older than 50 years of age and amyloids in the discs of individuals older than 40 years of age. In 261 intervertebral disc tissue specimens collected at the time of surgery for disc herniation, lipofuscin was seen in the discs of individuals older than 20 years of age and amyloids in the discs of individuals older than 15 years of age. It is speculated that amyloids and lipofuscin are a sign of aging in the intervertebral disc as in other tissues. Furthermore, amyloids and lipofuscin were seen in the operated discs of young individuals than in the autopsy cases."} {"id": "PMID:1279817", "title": "Chronic benign cervical pain syndromes. Surgical considerations.", "content": "The results of surgical intervention for chronic benign pain syndromes are generally poor. In this review, pertinent ablative and modulatory techniques are reviewed, with specific reference to their utility for benign pain syndromes. With the possible exception of facet rhizotomy, the ablative modalities have little role in the management of benign pain syndromes. The more extensive techniques of cordotomy, dorsal root entry zone lesioning, ganglionectomy, and rhizotomy, have erratic results and high rates of complication. No long-term studies exist to support the use of facet rhizotomy. It is minimally invasive, however, and has little morbidity. In patients with benign refractory posterior column pain, facet rhizotomy may be worth consideration. Modulatory devices may have a role in benign pain syndromes. While the use of indwelling epidural catheters remains investigational, dorsal column stimulation has been widely studied. In representative reports, significant pain relief has been observed in up to 60% of patients (mean follow-up of two years). In the carefully selected patient, this may represent a valuable therapeutic adjunct.", "contents": "Chronic benign cervical pain syndromes. Surgical considerations. The results of surgical intervention for chronic benign pain syndromes are generally poor. In this review, pertinent ablative and modulatory techniques are reviewed, with specific reference to their utility for benign pain syndromes. With the possible exception of facet rhizotomy, the ablative modalities have little role in the management of benign pain syndromes. The more extensive techniques of cordotomy, dorsal root entry zone lesioning, ganglionectomy, and rhizotomy, have erratic results and high rates of complication. No long-term studies exist to support the use of facet rhizotomy. It is minimally invasive, however, and has little morbidity. In patients with benign refractory posterior column pain, facet rhizotomy may be worth consideration. Modulatory devices may have a role in benign pain syndromes. While the use of indwelling epidural catheters remains investigational, dorsal column stimulation has been widely studied. In representative reports, significant pain relief has been observed in up to 60% of patients (mean follow-up of two years). In the carefully selected patient, this may represent a valuable therapeutic adjunct."} {"id": "PMID:1279819", "title": "[A case of systemic lupus erythematosus complicated with monoclonal CD5 + B cell proliferation suspected as chronic lymphocytic leukemia].", "content": "A case of systemic lupus erythematosus (SLE) complicated with monoclonal CD5 + B cell proliferation in peripheral blood and bone marrow is reported. A 59-year-old man suffering from left chest pain was admitted to the hospital because of thrombocytopenia (platelets 1.9 x 10(4)/mm3). The diagnosis of SLE was made from (1) pleuritis (2) autoimmune thrombocytopenia (3) positive anti-DNA antibodies, positive LE cell preparation (4) positive antinuclear antibodies. Prednisolone 60mg per day was started. From that time monoclonal CD5 + B cells began to increase in peripheral blood (maximum lymphocyte counts 11000/mm3, CD5 + B cells 77.6%) and bone marrow, and the complication of chronic lymphocytic leukemia (CLL) was suspected. It is said that patients of CLL often have various autoantibodies, and in about 15% of CLL patients complicate autoimmune hemolytic anemia, but those who develop collagen diseases are rare. And while lymphoid malignancies occur more often in the patients of SLE in comparison with normal subjects, the reports of the patients who complicate the proliferation of monoclonal CD5 + B cells like CLL are very few. But from many facts that indicate the relation between CD5 + B cell or its proliferation and the production of autoantibodies or autoimmune diseases, we consider this case worth to be reported.", "contents": "[A case of systemic lupus erythematosus complicated with monoclonal CD5 + B cell proliferation suspected as chronic lymphocytic leukemia]. A case of systemic lupus erythematosus (SLE) complicated with monoclonal CD5 + B cell proliferation in peripheral blood and bone marrow is reported. A 59-year-old man suffering from left chest pain was admitted to the hospital because of thrombocytopenia (platelets 1.9 x 10(4)/mm3). The diagnosis of SLE was made from (1) pleuritis (2) autoimmune thrombocytopenia (3) positive anti-DNA antibodies, positive LE cell preparation (4) positive antinuclear antibodies. Prednisolone 60mg per day was started. From that time monoclonal CD5 + B cells began to increase in peripheral blood (maximum lymphocyte counts 11000/mm3, CD5 + B cells 77.6%) and bone marrow, and the complication of chronic lymphocytic leukemia (CLL) was suspected. It is said that patients of CLL often have various autoantibodies, and in about 15% of CLL patients complicate autoimmune hemolytic anemia, but those who develop collagen diseases are rare. And while lymphoid malignancies occur more often in the patients of SLE in comparison with normal subjects, the reports of the patients who complicate the proliferation of monoclonal CD5 + B cells like CLL are very few. But from many facts that indicate the relation between CD5 + B cell or its proliferation and the production of autoantibodies or autoimmune diseases, we consider this case worth to be reported."} {"id": "PMID:1279820", "title": "The impact of a family-centered case management approach.", "content": "Two urban programs of family-centered case management services were established for families of children with both a developmental disability and a chronic health condition. These are children who present significant caregiving demands due to the long-term and severe nature of their disabilities. Thirty-two mothers were interviewed within the family's first month in the project and reinterviewed approximately one year later. The results indicate that more families received respite care, nursing services, training in the care of the child, educational services and transportation to school at follow-up than had been receiving those services at baseline. However, families still indicated high service needs for recreational activities, life planning, regular day care, legal services, and speech therapy at follow-up. Mothers indicated that program services were helpful in obtaining services, financing, information, support, and advocacy. Although maternal life satisfaction improved with program participation, non-handicapped siblings continued to have difficulties coping. The model employed is described and the practice and policy implications of the findings discussed.", "contents": "The impact of a family-centered case management approach. Two urban programs of family-centered case management services were established for families of children with both a developmental disability and a chronic health condition. These are children who present significant caregiving demands due to the long-term and severe nature of their disabilities. Thirty-two mothers were interviewed within the family's first month in the project and reinterviewed approximately one year later. The results indicate that more families received respite care, nursing services, training in the care of the child, educational services and transportation to school at follow-up than had been receiving those services at baseline. However, families still indicated high service needs for recreational activities, life planning, regular day care, legal services, and speech therapy at follow-up. Mothers indicated that program services were helpful in obtaining services, financing, information, support, and advocacy. Although maternal life satisfaction improved with program participation, non-handicapped siblings continued to have difficulties coping. The model employed is described and the practice and policy implications of the findings discussed."} {"id": "PMID:1279818", "title": "[The patient with incurable cancer and palliative medicine in Mexico].", "content": "This paper analyzes the potential advantages of palliative care for cancer patients in Mexico. The increasing incidence of cancer, the limited rate of cure of the most frequent cancers and limited resources make palliative care a realistic treatment option. In accordance to World Health Organization recommendations, I propose the development of palliative care in Mexico.", "contents": "[The patient with incurable cancer and palliative medicine in Mexico]. This paper analyzes the potential advantages of palliative care for cancer patients in Mexico. The increasing incidence of cancer, the limited rate of cure of the most frequent cancers and limited resources make palliative care a realistic treatment option. In accordance to World Health Organization recommendations, I propose the development of palliative care in Mexico."} {"id": "PMID:1279821", "title": "A double-blinded multicenter trial of somatostatin in the treatment of acute pancreatitis.", "content": "To evaluate the effect of somatostatin in the treatment of acute pancreatitis, 63 patients were randomly allocated to continuous intravenous infusion for three days of 250 micrograms of somatostatin (Dura Scan, Odense, Denmark) per hour (n = 33), or placebo (n = 30). Patients with a first attack of pancreatitis, serum amylase level of more than 450 units per liter and symptoms for less than 24 hours were eligible for participation in the study. Apart from a slightly significant faster decrease in serum amylase concentrations, we were unable to demonstrate any significant benefit from somatostatin with regard to paraclinical values and clinical course.", "contents": "A double-blinded multicenter trial of somatostatin in the treatment of acute pancreatitis. To evaluate the effect of somatostatin in the treatment of acute pancreatitis, 63 patients were randomly allocated to continuous intravenous infusion for three days of 250 micrograms of somatostatin (Dura Scan, Odense, Denmark) per hour (n = 33), or placebo (n = 30). Patients with a first attack of pancreatitis, serum amylase level of more than 450 units per liter and symptoms for less than 24 hours were eligible for participation in the study. Apart from a slightly significant faster decrease in serum amylase concentrations, we were unable to demonstrate any significant benefit from somatostatin with regard to paraclinical values and clinical course."} {"id": "PMID:1279822", "title": "Intraarterial 5-FU-infusion and simultaneous radiotherapy as palliative treatment of recurrent rectal cancer.", "content": "Palliative treatment of recurrent rectal cancer remains to be a challenge. From 1989 to 1991 13 patients with recurrent rectal cancer were treated with intraarterial infusion of 5-Fluorouracil and simultaneous radiotherapy in a palliative intent. Seven patients had received postoperative adjuvant radiotherapy with 56 to 60 Gy. Three patients had been treated with systemic chemotherapy. Radiotherapy of the recurrence was performed with 19.8 to 30.6 Gy in the pre-irradiated patients and with 50.4 to 59.4 Gy in the others. One complete remission, three partial remissions and nine minor responses were observed. Three patients had complete pain relief after the treatment, in the remaining patients major pain reduction was achieved. Palliation lasted from three to twelve months (median: five months). Our results indicate that locoregional chemo- and radiotherapy are a effective modality in recurrent rectal cancer.", "contents": "Intraarterial 5-FU-infusion and simultaneous radiotherapy as palliative treatment of recurrent rectal cancer. Palliative treatment of recurrent rectal cancer remains to be a challenge. From 1989 to 1991 13 patients with recurrent rectal cancer were treated with intraarterial infusion of 5-Fluorouracil and simultaneous radiotherapy in a palliative intent. Seven patients had received postoperative adjuvant radiotherapy with 56 to 60 Gy. Three patients had been treated with systemic chemotherapy. Radiotherapy of the recurrence was performed with 19.8 to 30.6 Gy in the pre-irradiated patients and with 50.4 to 59.4 Gy in the others. One complete remission, three partial remissions and nine minor responses were observed. Three patients had complete pain relief after the treatment, in the remaining patients major pain reduction was achieved. Palliation lasted from three to twelve months (median: five months). Our results indicate that locoregional chemo- and radiotherapy are a effective modality in recurrent rectal cancer."} {"id": "PMID:1279823", "title": "[Disorders of the protease-antiprotease system of a bronchial washout in patients with bronchiectasis and the means for their correction].", "content": "Patients with bronchiectatic disease show imbalance between the activity of proteolytic enzymes and their inhibitors contained by bronchial wash-out, manifesting in a reduction of the inhibitory potential and a rise of the activity of trypsin-like proteinases. After the standard basic treatment the protease-antiprotease system in bronchial wash-out shows a definite improvement. Endobronchial therapy with contrykal given in a dose of 20-30 thousand ATpE for 5-7 days does not ameliorate imbalance in the protease-antiprotease system in bronchiectatic disease patients as compared to the common basic therapy.", "contents": "[Disorders of the protease-antiprotease system of a bronchial washout in patients with bronchiectasis and the means for their correction]. Patients with bronchiectatic disease show imbalance between the activity of proteolytic enzymes and their inhibitors contained by bronchial wash-out, manifesting in a reduction of the inhibitory potential and a rise of the activity of trypsin-like proteinases. After the standard basic treatment the protease-antiprotease system in bronchial wash-out shows a definite improvement. Endobronchial therapy with contrykal given in a dose of 20-30 thousand ATpE for 5-7 days does not ameliorate imbalance in the protease-antiprotease system in bronchiectatic disease patients as compared to the common basic therapy."} {"id": "PMID:1279824", "title": "[The immediate and late results of treating patients with nonspecific lung diseases by using the local administration of kontrikal and antibiotics].", "content": "An analysis was made of the short- and long-term (1.5-2 years) results of the treatment of 75 patients with acute abscess and 101 with lingering pneumonia using different routes of administration of proteinase inhibitors and antibiotics. The high efficacy was demonstrated of the local intrapulmonary and endobronchial administration of the proteinase inhibitor contrykal and antibiotics. The treatment method suggested was found to compare favourably with the common route of the drug administration. The treatment is well tolerated and promotes the shortening of the times of the patients' stay in the hospital, reduces the number of complications and residual phenomena, prevents the disease relapses and their transformation to chronic nonspecific pulmonary diseases. The clinical recovery of the patients with acute lung abscess was reached in 91.4% of cases whereas in the reference group, only in 66.7%. In the patients with lingering pneumonia, the recovery was noted in 85.4%, in the reference group, in 27.5% of cases.", "contents": "[The immediate and late results of treating patients with nonspecific lung diseases by using the local administration of kontrikal and antibiotics]. An analysis was made of the short- and long-term (1.5-2 years) results of the treatment of 75 patients with acute abscess and 101 with lingering pneumonia using different routes of administration of proteinase inhibitors and antibiotics. The high efficacy was demonstrated of the local intrapulmonary and endobronchial administration of the proteinase inhibitor contrykal and antibiotics. The treatment method suggested was found to compare favourably with the common route of the drug administration. The treatment is well tolerated and promotes the shortening of the times of the patients' stay in the hospital, reduces the number of complications and residual phenomena, prevents the disease relapses and their transformation to chronic nonspecific pulmonary diseases. The clinical recovery of the patients with acute lung abscess was reached in 91.4% of cases whereas in the reference group, only in 66.7%. In the patients with lingering pneumonia, the recovery was noted in 85.4%, in the reference group, in 27.5% of cases."} {"id": "PMID:1279826", "title": "[The clinico-laboratory dynamics in the reaferon treatment of glomerulonephritis patients with the nephrotic syndrome].", "content": "Overall 40 chronic glomerulonephritis patients with nephrotic syndrome were treated by reaferon. All the patients underwent clinical and laboratory examinations and nephric biopsy. As a result of the treatment, all the patients demonstrated an increase of the level of glomerular filtration, stabilization of protein and lipid metabolism along with the lowering of diurnal proteinuria. Reaferon exerted a beneficial effect on cellular factors of immunity. In some cases, the use of reaferon can be a definite alternative of the conventional treatment methods.", "contents": "[The clinico-laboratory dynamics in the reaferon treatment of glomerulonephritis patients with the nephrotic syndrome]. Overall 40 chronic glomerulonephritis patients with nephrotic syndrome were treated by reaferon. All the patients underwent clinical and laboratory examinations and nephric biopsy. As a result of the treatment, all the patients demonstrated an increase of the level of glomerular filtration, stabilization of protein and lipid metabolism along with the lowering of diurnal proteinuria. Reaferon exerted a beneficial effect on cellular factors of immunity. In some cases, the use of reaferon can be a definite alternative of the conventional treatment methods."} {"id": "PMID:1279831", "title": "Activation of coagulation and fibrinolysis following OKT3 administration to renal transplant recipients: association with distinct mediators.", "content": "Treatment with OKT3 induces cytokine release and activates the complement system. Since both phenomena may affect coagulation and fibrinolysis we studied these systems in 8 renal transplant recipients during OKT3 treatment. In 8 of 9 patients a similar pattern was observed: plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-alpha 2-antiplasmin-complex levels were increased as compared to pretreatment levels (p less than 0.05) at 15 min after the first OKT3 dose and reached peak values at 1 h. No significant changes were observed upon subsequent OKT3 administrations or in a control group of 8 patients. In one patient upon the first OKT3 administration only complement activation, and no cytokine release was observed, whereas plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-alpha 2-antiplasmin-complex levels increased only at 15 min. In conclusion, we demonstrate a biphasic activation of coagulation and fibrinolysis upon the first OKT3 dose; the initial phase seems to be associated with complement activation, the later phase with cytokine release.", "contents": "Activation of coagulation and fibrinolysis following OKT3 administration to renal transplant recipients: association with distinct mediators. Treatment with OKT3 induces cytokine release and activates the complement system. Since both phenomena may affect coagulation and fibrinolysis we studied these systems in 8 renal transplant recipients during OKT3 treatment. In 8 of 9 patients a similar pattern was observed: plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-alpha 2-antiplasmin-complex levels were increased as compared to pretreatment levels (p less than 0.05) at 15 min after the first OKT3 dose and reached peak values at 1 h. No significant changes were observed upon subsequent OKT3 administrations or in a control group of 8 patients. In one patient upon the first OKT3 administration only complement activation, and no cytokine release was observed, whereas plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-alpha 2-antiplasmin-complex levels increased only at 15 min. In conclusion, we demonstrate a biphasic activation of coagulation and fibrinolysis upon the first OKT3 dose; the initial phase seems to be associated with complement activation, the later phase with cytokine release."} {"id": "PMID:1279832", "title": "Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin.", "content": "Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis.", "contents": "Platelet factor XIII increases the fibrinolytic resistance of platelet-rich clots by accelerating the crosslinking of alpha 2-antiplasmin to fibrin. Platelet clots resist fibrinolysis by plasminogen activators. We hypothesized that platelet factor XIII may enhance the fibrinolytic resistance of platelet-rich clots by catalyzing the crosslinking of alpha 2-antiplasmin (alpha 2AP) to fibrin. Analysis of plasma clot structure by polyacrylamide gel electrophoresis and immunoblotting revealed accelerated alpha 2AP-fibrin crosslinking in platelet-rich compared with platelet-depleted plasma clots. A similar study of clots formed with purified fibrinogen (depleted of factor XIII activity), isolated platelets, and specific factor XIII inhibitors indicated that this accelerated crosslinking was due to the catalytic activity of platelet factor XIII. Moreover, when washed platelets were aggregated by thrombin, there was evidence of platelet factor XIII-mediated crosslinking between platelet alpha 2AP and platelet fibrin(ogen). Specific inhibition (by a monoclonal antibody) of the alpha 2AP associated with washed platelet aggregates accelerated the fibrinolysis of the platelet aggregate. Thus in platelet-rich plasma clots, and in thrombin-induced platelet aggregates, platelet factor XIII actively formed alpha 2AP-fibrin crosslinks, which appeared to enhance the resistance of platelet-rich clots to fibrinolysis."} {"id": "PMID:1279834", "title": "Effect of sodium pentosan polysulphate on the thrombogenicity of prothrombin complex concentrates.", "content": "The addition of pentosan polysulphate sodium (NaPPS) to thrombogenic prothrombin complex concentrates (PCC) dose-dependently reduces or abolishes thrombus formation in rats in the stasis model acc. to Wessler. However, no reduction of thrombogenicity was found in PCC preparations manufactured in the presence of NaPPS.", "contents": "Effect of sodium pentosan polysulphate on the thrombogenicity of prothrombin complex concentrates. The addition of pentosan polysulphate sodium (NaPPS) to thrombogenic prothrombin complex concentrates (PCC) dose-dependently reduces or abolishes thrombus formation in rats in the stasis model acc. to Wessler. However, no reduction of thrombogenicity was found in PCC preparations manufactured in the presence of NaPPS."} {"id": "PMID:1279835", "title": "Fibrinolytic effects of pro-urokinase combined with low-dose urokinase compared to high-dose urokinase in patients with acute myocardial infarction.", "content": "20 patients (6 females, 14 males) aged between 47 and and 75 years (mean: 62.6 yrs.) with acute myocardial infarction (onset of symptoms within 6 hours) were treated intravenously with either 200,000 U urokinase (UK) and 4.5 million U pro-urokinase (pro-UK) within 60 min (group I, N = 10), or 2.5 million U UK within 5 min (group II, N = 10). Blood samples for haemostatic and fibrinolytic function tests were taken prior to and repeatedly during the 24 hours following treatment. Peak fibrinolytic activity measured by fibrin plates was equivalent in both regimens. Average decreases, with lowest levels within 60 to 120 min following thrombolytic therapy, were observed of 27% and 70% for plasminogen, of 71% and 91% for alpha-2-antiplasmin, and of 20% and 74% for fibrinogen in group I and II, respectively. The reptilase time reached maximum values of 1.5- and 4.5-fold within 60 to 180 min. Peak levels of D-dimers and thrombin-antithrombin III complexes in group II were 2.6 and 3.2 times those of group I. After 24 hours, in contrast to group I, all these parameters still remained significantly different from pretreatment values in group II. These data indicate that, contrary to high-dose UK, pro-UK in combination with low-dose UK causes minor systemic fibrinolytic effects and is, therefore, assumed to be largely clot-specific, although the fibrinolytic potential is equivalent for both regimens.", "contents": "Fibrinolytic effects of pro-urokinase combined with low-dose urokinase compared to high-dose urokinase in patients with acute myocardial infarction. 20 patients (6 females, 14 males) aged between 47 and and 75 years (mean: 62.6 yrs.) with acute myocardial infarction (onset of symptoms within 6 hours) were treated intravenously with either 200,000 U urokinase (UK) and 4.5 million U pro-urokinase (pro-UK) within 60 min (group I, N = 10), or 2.5 million U UK within 5 min (group II, N = 10). Blood samples for haemostatic and fibrinolytic function tests were taken prior to and repeatedly during the 24 hours following treatment. Peak fibrinolytic activity measured by fibrin plates was equivalent in both regimens. Average decreases, with lowest levels within 60 to 120 min following thrombolytic therapy, were observed of 27% and 70% for plasminogen, of 71% and 91% for alpha-2-antiplasmin, and of 20% and 74% for fibrinogen in group I and II, respectively. The reptilase time reached maximum values of 1.5- and 4.5-fold within 60 to 180 min. Peak levels of D-dimers and thrombin-antithrombin III complexes in group II were 2.6 and 3.2 times those of group I. After 24 hours, in contrast to group I, all these parameters still remained significantly different from pretreatment values in group II. These data indicate that, contrary to high-dose UK, pro-UK in combination with low-dose UK causes minor systemic fibrinolytic effects and is, therefore, assumed to be largely clot-specific, although the fibrinolytic potential is equivalent for both regimens."} {"id": "PMID:1279836", "title": "Autoactivation of human blood coagulation factor XII on dextran derivatives of different molecular weight.", "content": "We prepared a derivative of dextran T40 (average M(r) 43,000) from which fractions of different M(r) but with equal charge density were obtained and tested for their ability to promote autoactivation of human blood coagulation factor XII. The mechanism of autoactivation appeared dependent upon the M(r) of the polymer used. Thus, with polymers of 38,000 M(r) or higher only alpha-factor XIIa was formed and the reaction could be completely described in terms of a simple second-order mechanism of autoactivation. With smaller polymer molecules beta-factor XIIa became a major reaction product and as a result of this the autoactivation kinetics did not adhere to the second-order mechanisms thus far described.", "contents": "Autoactivation of human blood coagulation factor XII on dextran derivatives of different molecular weight. We prepared a derivative of dextran T40 (average M(r) 43,000) from which fractions of different M(r) but with equal charge density were obtained and tested for their ability to promote autoactivation of human blood coagulation factor XII. The mechanism of autoactivation appeared dependent upon the M(r) of the polymer used. Thus, with polymers of 38,000 M(r) or higher only alpha-factor XIIa was formed and the reaction could be completely described in terms of a simple second-order mechanism of autoactivation. With smaller polymer molecules beta-factor XIIa became a major reaction product and as a result of this the autoactivation kinetics did not adhere to the second-order mechanisms thus far described."} {"id": "PMID:1279837", "title": "The effect of fasting and cholecystokinin stimulation on normal and neoplastic tissue in the rat pancreas.", "content": "Pancreatic nodules were produced in rats by either feeding raw soya flour alone or by injection of azaserine plus raw soya flour feeding. The resulting nodules were studied to determine whether there was any functional difference between this tissue and the relatively normal internodular pancreas. Tissue DNA and trypsin content were significantly elevated in nodules compared to the adjacent tissue. With fasting, protein and enzyme content increased significantly and equally in both nodular and internodular tissues. RNA levels fell significantly and the decrease was more pronounced in nodular tissue. The responsiveness of the multinodular pancreas to cholecystokinin was examined by measuring pancreatic secretion basally and in response to cholecystokinin. Both the volume and protein content secreted by the multinodular pancreas were greatly elevated above control levels. When corrected for pancreatic weight, the difference remained significant and appeared to be due to increased basal secretion by the nodular pancreas. These studies demonstrate that azaserine-raw soya flour induced nodules are functionally efficient. Furthermore, the secretory response to cholecystokinin of these nodules is equal to or higher than that of normal tissue.", "contents": "The effect of fasting and cholecystokinin stimulation on normal and neoplastic tissue in the rat pancreas. Pancreatic nodules were produced in rats by either feeding raw soya flour alone or by injection of azaserine plus raw soya flour feeding. The resulting nodules were studied to determine whether there was any functional difference between this tissue and the relatively normal internodular pancreas. Tissue DNA and trypsin content were significantly elevated in nodules compared to the adjacent tissue. With fasting, protein and enzyme content increased significantly and equally in both nodular and internodular tissues. RNA levels fell significantly and the decrease was more pronounced in nodular tissue. The responsiveness of the multinodular pancreas to cholecystokinin was examined by measuring pancreatic secretion basally and in response to cholecystokinin. Both the volume and protein content secreted by the multinodular pancreas were greatly elevated above control levels. When corrected for pancreatic weight, the difference remained significant and appeared to be due to increased basal secretion by the nodular pancreas. These studies demonstrate that azaserine-raw soya flour induced nodules are functionally efficient. Furthermore, the secretory response to cholecystokinin of these nodules is equal to or higher than that of normal tissue."} {"id": "PMID:1279838", "title": "Comparative characterization of two toxic phospholipases A2 from Indian cobra (Naja naja naja) venom.", "content": "Indian cobra venom contains many phospholipase A2 (PLA2) toxins. In the present study two toxic PLA2s have been purified from the Indian cobra (Naja naja naja) venom by column chromatography. The NN-XIa-and NN-XIb-PLA2s have mol. wts between 10,700 and 15,000. The NN-XIa-PLA2 induces myotoxic effects, oedema and neurotoxicity in mice and has an i.p. LD50 of 8.5 mg/kg body weight. The NN-XIa-PLA2 is also cytotoxic to Ehrlich ascites tumour cells. The other PLA2, NN-XIb, in contrast has an i.p. LD50 of 0.22 mg/kg body weight, and it induces acute neurotoxicity. The NN-XIb-PLA2 is devoid of the other biological activities which are exhibited by NN-XIa-PLA2.", "contents": "Comparative characterization of two toxic phospholipases A2 from Indian cobra (Naja naja naja) venom. Indian cobra venom contains many phospholipase A2 (PLA2) toxins. In the present study two toxic PLA2s have been purified from the Indian cobra (Naja naja naja) venom by column chromatography. The NN-XIa-and NN-XIb-PLA2s have mol. wts between 10,700 and 15,000. The NN-XIa-PLA2 induces myotoxic effects, oedema and neurotoxicity in mice and has an i.p. LD50 of 8.5 mg/kg body weight. The NN-XIa-PLA2 is also cytotoxic to Ehrlich ascites tumour cells. The other PLA2, NN-XIb, in contrast has an i.p. LD50 of 0.22 mg/kg body weight, and it induces acute neurotoxicity. The NN-XIb-PLA2 is devoid of the other biological activities which are exhibited by NN-XIa-PLA2."} {"id": "PMID:1279839", "title": "Experimental treatment protocols for scorpion envenomation: a review of common therapies and an effect of kallikrein-kinin inhibitors.", "content": "Nine fatal cases from the sting of the scorpion Leiurus quinquestriatus are presented. All victims showed association of CNS and cardiovascular manifestations. Either the CNS or the cardiovascular effects could occur first in the early phases of the scorpion envenoming syndrome; the CNS manifestations, however, always preceded the terminal hypotension and cardiac arrest. Pharmacokinetic studies in rabbits following s.c. injection of the labelled venom showed that rapid absorption took place with about 70% of the maximum blood concentration reached within 15 min. Intramuscular injection of antivenom did not significantly affect the absorption of the venom or the other pharmacokinetic parameters. The total area under concentration time curve was not significantly different from that following i.v. injection, showing that nearly complete absorption of the venom from the s.c. site would occur in 7-8 hr. The i.v. infusion of venom into anaesthetized rats, at a rate comparable to the absorption rate from s.c. sites, allowed the determination of the minimum lethal dose (MLD) with reasonable accuracy. In rescue experiments, anaesthetized rats were injected s.c. with multiple MLD of venom and infused i.v. with drugs commonly used in the treatment of scorpion envenomation. The prepared potent specific antivenoms, but not the commercial polyvalent antivenom, rescued all animals from the lethal effect of the venom, even when injected late. Atropine, atropine+phentolamine, chlorpromazine, hydrocortisone and indomethacin were able, in varying degrees, to rescue some rats injected with 2 MLD of venom. Phentolamine, propranolol, hydralazine and calcium gluconate significantly prolonged the survival time, but did not rescue any animals. Chlorpheniramine, saline and 1/4 saline + 5% dextrose were without any effect. Aprotinin, the kallikrein-kinin inhibitor, was able to rescue half of the animals from the lethal action of the venom. Electrocardiographic studies showed that L. quinquestriatus venom, irrespective of the route of administration, causes myocardial ischaemia and either inferior or anterior wall infarction. This was associated with an initial moderate and a terminal severe bradycardia together with a variety of rhythm and conduction defects. Except for minor and transient electrocardiographic changes, either the prepared antivenoms or aprotinin protected rabbits and rats from the cardiac effects of the venom.", "contents": "Experimental treatment protocols for scorpion envenomation: a review of common therapies and an effect of kallikrein-kinin inhibitors. Nine fatal cases from the sting of the scorpion Leiurus quinquestriatus are presented. All victims showed association of CNS and cardiovascular manifestations. Either the CNS or the cardiovascular effects could occur first in the early phases of the scorpion envenoming syndrome; the CNS manifestations, however, always preceded the terminal hypotension and cardiac arrest. Pharmacokinetic studies in rabbits following s.c. injection of the labelled venom showed that rapid absorption took place with about 70% of the maximum blood concentration reached within 15 min. Intramuscular injection of antivenom did not significantly affect the absorption of the venom or the other pharmacokinetic parameters. The total area under concentration time curve was not significantly different from that following i.v. injection, showing that nearly complete absorption of the venom from the s.c. site would occur in 7-8 hr. The i.v. infusion of venom into anaesthetized rats, at a rate comparable to the absorption rate from s.c. sites, allowed the determination of the minimum lethal dose (MLD) with reasonable accuracy. In rescue experiments, anaesthetized rats were injected s.c. with multiple MLD of venom and infused i.v. with drugs commonly used in the treatment of scorpion envenomation. The prepared potent specific antivenoms, but not the commercial polyvalent antivenom, rescued all animals from the lethal effect of the venom, even when injected late. Atropine, atropine+phentolamine, chlorpromazine, hydrocortisone and indomethacin were able, in varying degrees, to rescue some rats injected with 2 MLD of venom. Phentolamine, propranolol, hydralazine and calcium gluconate significantly prolonged the survival time, but did not rescue any animals. Chlorpheniramine, saline and 1/4 saline + 5% dextrose were without any effect. Aprotinin, the kallikrein-kinin inhibitor, was able to rescue half of the animals from the lethal action of the venom. Electrocardiographic studies showed that L. quinquestriatus venom, irrespective of the route of administration, causes myocardial ischaemia and either inferior or anterior wall infarction. This was associated with an initial moderate and a terminal severe bradycardia together with a variety of rhythm and conduction defects. Except for minor and transient electrocardiographic changes, either the prepared antivenoms or aprotinin protected rabbits and rats from the cardiac effects of the venom."} {"id": "PMID:1279841", "title": "Lack of dexamethasone modulation of mRNAs involved in the glucocorticoid signal transduction pathway in two cell systems.", "content": "Glucocorticoids are final effectors of the stress response. These hormones exert negative feedback action at multiple levels of the hypothalamic-pituitary-adrenal axis and regulate a large number of central nervous system and peripheral target genes. The inactive form of the glucocorticoid receptor in the cytoplasm appears to be bound to heat shock proteins of the 90K family (hsp90 alpha and hsp90 beta). This interaction facilitates binding of glucocorticoid to its receptor and, therefore, its activation. The chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds on a negative glucocorticoid response element in the 5' regulatory region of the proopiomelanocortin gene and prevents the repressive effect of glucocorticoids on this gene. The aim of this study was to examine the effect of glucocorticoids on the steady-state mRNAs of their own receptor, the two hsp90s, and COUP-TF. Quantitative Northern blot analysis in primary leukocytes and Epstein-Barr virus-transformed human lymphocytes (EBV-THL) basally and after a 24-hour exposure to 50 nM dexamethasone was performed. Treatment of primary leukocytes or normally growing EBV-THL with dexamethasone had no effect on the mRNA level of glucocorticoid receptor, hsp90 alpha, hsp90 beta, or COUP-TF. Similar treatment of EBV-THL grown in charcoal-stripped media, resulted in minimal changes in the mRNAs of these factors. Our findings suggest that glucocorticoids do not regulate the steady-state mRNA levels of these core components of the mammalian stress response in human primary and Epstein-Barr virus-transformed lymphocytes.", "contents": "Lack of dexamethasone modulation of mRNAs involved in the glucocorticoid signal transduction pathway in two cell systems. Glucocorticoids are final effectors of the stress response. These hormones exert negative feedback action at multiple levels of the hypothalamic-pituitary-adrenal axis and regulate a large number of central nervous system and peripheral target genes. The inactive form of the glucocorticoid receptor in the cytoplasm appears to be bound to heat shock proteins of the 90K family (hsp90 alpha and hsp90 beta). This interaction facilitates binding of glucocorticoid to its receptor and, therefore, its activation. The chicken ovalbumin upstream promoter transcription factor (COUP-TF) binds on a negative glucocorticoid response element in the 5' regulatory region of the proopiomelanocortin gene and prevents the repressive effect of glucocorticoids on this gene. The aim of this study was to examine the effect of glucocorticoids on the steady-state mRNAs of their own receptor, the two hsp90s, and COUP-TF. Quantitative Northern blot analysis in primary leukocytes and Epstein-Barr virus-transformed human lymphocytes (EBV-THL) basally and after a 24-hour exposure to 50 nM dexamethasone was performed. Treatment of primary leukocytes or normally growing EBV-THL with dexamethasone had no effect on the mRNA level of glucocorticoid receptor, hsp90 alpha, hsp90 beta, or COUP-TF. Similar treatment of EBV-THL grown in charcoal-stripped media, resulted in minimal changes in the mRNAs of these factors. Our findings suggest that glucocorticoids do not regulate the steady-state mRNA levels of these core components of the mammalian stress response in human primary and Epstein-Barr virus-transformed lymphocytes."} {"id": "PMID:1279842", "title": "Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats.", "content": "Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed. Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n = 5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 mg/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted. Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean +/- SEM baseline, 1.86 +/- 0.25 pmol/ml perfusate; during ischemia, 8.14 +/- 0.89 pmol/ml; p < 0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98 +/- 0.15 pmol/ml; ischemia, 24.4 +/- 5.93 pmol/ml; p < 0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34 +/- 16 normal-appearing neurons, middle, 52.2 +/- 22.9 neurons; lateral, 56.6 +/- 21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6 +/- 6.5 neurons; middle, 131.4 +/- 4.9 neurons; lateral, 130 +/- 7.5 neurons; p < 0.01 different from nontreated). Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage.", "contents": "Ischemia-induced extracellular release of serotonin plays a role in CA1 neuronal cell death in rats. Serotonin, via 5-HT2 receptors, exerts an excitatory effect on CA1 neurons and may play a role in ischemia-induced excitotoxic damage. To evaluate the role of serotonin in ischemia, both neurochemical and histopathological studies were performed. Neurochemical studies included rats that were subjected to 12.5 or 20 minutes of normothermic ischemia by two-vessel occlusion plus hypotension, and extracellular serotonin levels were measured in the hippocampus (12.5 minutes' ischemia, n = 5) or striatum (20 minutes' ischemia, n = 13) by microdialysis. In the histopathological study the effect of 8 mg/kg ritanserin, a 5-HT2 antagonist, administered continuously from 30 minutes prior to ischemia until 1 hour of recirculation was evaluated in five rats subjected to 10 minutes of ischemia. After 3 days, the numbers of normal-appearing neurons in the CA1 subregions were counted. Ischemia of 12.5 minutes' duration induced a fourfold increase in serotonin in the hippocampus (mean +/- SEM baseline, 1.86 +/- 0.25 pmol/ml perfusate; during ischemia, 8.14 +/- 0.89 pmol/ml; p < 0.05 by analysis of variance). Twenty minutes of ischemia induced a 25-fold increase in serotonin in the dorsolateral striatum (baseline, 0.98 +/- 0.15 pmol/ml; ischemia, 24.4 +/- 5.93 pmol/ml; p < 0.001). The histopathological study demonstrated severe ischemic damage in all CA1 subregions of nontreated animals (medial, 34 +/- 16 normal-appearing neurons, middle, 52.2 +/- 22.9 neurons; lateral, 56.6 +/- 21.8 neurons). Treatment with ritanserin significantly attenuated ischemic damage (medial, 117.6 +/- 6.5 neurons; middle, 131.4 +/- 4.9 neurons; lateral, 130 +/- 7.5 neurons; p < 0.01 different from nontreated). Taken together, these results suggest that serotonin plays a detrimental role, mediated by 5-HT2 receptors, in the development of ischemic damage."} {"id": "PMID:1279840", "title": "[The treatment of alveolar hemorrhages with helevin].", "content": "The author described the clinical results and the scheme of helevin therapy used to arrest bleedings from the well after removal of a tooth in 115 patients. The causes of the bleeding were of a general nature in 87 (75.7%) and local in 28 (24.3%) patients. The results were good when the bleeding was not severe (89.6% of cases) and poor when it was grave; in grave cases other methods of hemostasis should be resorted to.", "contents": "[The treatment of alveolar hemorrhages with helevin]. The author described the clinical results and the scheme of helevin therapy used to arrest bleedings from the well after removal of a tooth in 115 patients. The causes of the bleeding were of a general nature in 87 (75.7%) and local in 28 (24.3%) patients. The results were good when the bleeding was not severe (89.6% of cases) and poor when it was grave; in grave cases other methods of hemostasis should be resorted to."} {"id": "PMID:1279843", "title": "Effects of nicardipine on tube formation of bovine vascular endothelial cells in vitro.", "content": "The purpose of this study was to assess the effect of nicardipine, a Ca2+ channel blocker, on angiogenesis in vitro. Bovine carotid artery endothelial cells were cultured between type I collagen gel layers with 10(-9) to 10(-5) M nicardipine. The morphological changes were monitored by phase-contrast microscopy and photographed. The total length of tubular structures was measured with an image analyzer system. Endothelial proliferation and migration assays were also performed with the same doses of nicardipine. Cultured endothelial cells form tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9) to 10(-5) M nicardipine in a dose-dependent manner. Migration of endothelial cells was also suppressed by the same doses of nicardipine. However, proliferation of endothelial cells was not enhanced. Nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells. This result suggests that nicardipine may have therapeutic potential in angiogenic disorders such as tumor growth, atherogenesis, and diabetic retinopathy.", "contents": "Effects of nicardipine on tube formation of bovine vascular endothelial cells in vitro. The purpose of this study was to assess the effect of nicardipine, a Ca2+ channel blocker, on angiogenesis in vitro. Bovine carotid artery endothelial cells were cultured between type I collagen gel layers with 10(-9) to 10(-5) M nicardipine. The morphological changes were monitored by phase-contrast microscopy and photographed. The total length of tubular structures was measured with an image analyzer system. Endothelial proliferation and migration assays were also performed with the same doses of nicardipine. Cultured endothelial cells form tubular structures between collagen gel layers. Tube formation of endothelial cells was suppressed by culture with 10(-9) to 10(-5) M nicardipine in a dose-dependent manner. Migration of endothelial cells was also suppressed by the same doses of nicardipine. However, proliferation of endothelial cells was not enhanced. Nicardipine acts as an inhibitor of angiogenesis in vitro by inhibiting the migration of endothelial cells. This result suggests that nicardipine may have therapeutic potential in angiogenic disorders such as tumor growth, atherogenesis, and diabetic retinopathy."} {"id": "PMID:1279846", "title": "[Osteomyelitis in congenital analgesia].", "content": "Presentation of a case of a congenital analgia, who showed as a complication a chronical osteomyelitis of the mandible with formation of sequester and fracture. Partial resection of the mandible and immediate reconstruction was done performing simultaneously a rebuilding of the atrophied alveolus by the use of split ribs and fixation with a long miniplate.", "contents": "[Osteomyelitis in congenital analgesia]. Presentation of a case of a congenital analgia, who showed as a complication a chronical osteomyelitis of the mandible with formation of sequester and fracture. Partial resection of the mandible and immediate reconstruction was done performing simultaneously a rebuilding of the atrophied alveolus by the use of split ribs and fixation with a long miniplate."} {"id": "PMID:1279844", "title": "[The detection of group-specific antigens in hair after its contact with blood and ejaculate].", "content": "The aim of this study was the detection of AB0 antigens extrinsic for a person in his (her) hair. The hair was kept for 1-7 days in whole or diluted blood (96 experiments) and semen (11 experiments). Only the group-specific antigens, intrinsic for the subjects whose hair was examined, were detectable in the hair after this exposure.", "contents": "[The detection of group-specific antigens in hair after its contact with blood and ejaculate]. The aim of this study was the detection of AB0 antigens extrinsic for a person in his (her) hair. The hair was kept for 1-7 days in whole or diluted blood (96 experiments) and semen (11 experiments). Only the group-specific antigens, intrinsic for the subjects whose hair was examined, were detectable in the hair after this exposure."} {"id": "PMID:1279845", "title": "[The determination of buccal epithelial cells in forensic medical cytological research].", "content": "The morphology of isolated cells of multi-layer squamous non-horny epithelium (buccal, vaginal, urethral, rectal), stained with 0.05% nigrosine solution, was under study, and the sizes of these cells and their nuclei were measured. Specific markers were detected in the buccal epitheliocytes, that permit their reliable differentiation from other epitheliocytes studied by the size of the cells and nuclei, by a characteristic structure of the cytoplasm, etc. The findings may be used for the diagnosis of the origin of isolated cells of the buccal mucosa.", "contents": "[The determination of buccal epithelial cells in forensic medical cytological research]. The morphology of isolated cells of multi-layer squamous non-horny epithelium (buccal, vaginal, urethral, rectal), stained with 0.05% nigrosine solution, was under study, and the sizes of these cells and their nuclei were measured. Specific markers were detected in the buccal epitheliocytes, that permit their reliable differentiation from other epitheliocytes studied by the size of the cells and nuclei, by a characteristic structure of the cytoplasm, etc. The findings may be used for the diagnosis of the origin of isolated cells of the buccal mucosa."} {"id": "PMID:1279848", "title": "The acute effect of FK506 and cyclosporine on endothelial cell function and renal vascular resistance.", "content": "We have previously documented that cyclosporine exerts a direct cytotoxic effect on endothelial cells and causes an increase in renal vascular resistance (RVR) in the rat. In the present study we investigated whether FK506, a novel immunosuppressive agent thought to be less nephrotoxic than CsA, impairs endothelial cell function in vitro and affects RVR in vivo. In vitro eicosanoid release and endothelin release were measured in bovine aortic endothelial cells in culture exposed for 1, 6, and 24 hr to increasing concentrations of FK506 (1 nM to 10 microM) or CsA (0.5, 10 microM). No significant changes in TxB2 and 6-keto-PGF1 alpha (the stable breakdown products of TxA2 and PGI2, respectively) and endothelin release were found after 1 and 6 hr of incubation with all the concentrations of FK506 and CsA considered. FK506 did not affect endothelin release even after 24 hr of incubation. In contrast, cell exposure to CsA was associated with a dose-dependent increase in TxB2, 6-keto-PGF1 alpha, and endothelin release that reached statistical significance after incubation with 10 microM CsA. FK506 did not induce cell detachment or lysis at any concentration and time considered, while 10 microM CsA induced a significant reduction in cell count accompanied by cell lysis. In vivo studies showed that a single i.v. injection of FK506 to rats within a broad range of doses (28 ng/kg to 2.8 micrograms/kg) did not modify RVR. This was true even for a dose as high as 20 mg/kg, while 20 mg/kg CsA caused a dramatic increase in RVR. We conclude that FK506, unlike CsA, does not induce endothelial cell injury in vitro. Whether this explains the differences in renovascular resistance observed in vivo after acute injection of FK506 and CsA is an attractive possibility that needs to be further explored.", "contents": "The acute effect of FK506 and cyclosporine on endothelial cell function and renal vascular resistance. We have previously documented that cyclosporine exerts a direct cytotoxic effect on endothelial cells and causes an increase in renal vascular resistance (RVR) in the rat. In the present study we investigated whether FK506, a novel immunosuppressive agent thought to be less nephrotoxic than CsA, impairs endothelial cell function in vitro and affects RVR in vivo. In vitro eicosanoid release and endothelin release were measured in bovine aortic endothelial cells in culture exposed for 1, 6, and 24 hr to increasing concentrations of FK506 (1 nM to 10 microM) or CsA (0.5, 10 microM). No significant changes in TxB2 and 6-keto-PGF1 alpha (the stable breakdown products of TxA2 and PGI2, respectively) and endothelin release were found after 1 and 6 hr of incubation with all the concentrations of FK506 and CsA considered. FK506 did not affect endothelin release even after 24 hr of incubation. In contrast, cell exposure to CsA was associated with a dose-dependent increase in TxB2, 6-keto-PGF1 alpha, and endothelin release that reached statistical significance after incubation with 10 microM CsA. FK506 did not induce cell detachment or lysis at any concentration and time considered, while 10 microM CsA induced a significant reduction in cell count accompanied by cell lysis. In vivo studies showed that a single i.v. injection of FK506 to rats within a broad range of doses (28 ng/kg to 2.8 micrograms/kg) did not modify RVR. This was true even for a dose as high as 20 mg/kg, while 20 mg/kg CsA caused a dramatic increase in RVR. We conclude that FK506, unlike CsA, does not induce endothelial cell injury in vitro. Whether this explains the differences in renovascular resistance observed in vivo after acute injection of FK506 and CsA is an attractive possibility that needs to be further explored."} {"id": "PMID:1279849", "title": "Late-onset acute rejection in orthotopic liver transplantation--associated risk factors and outcome.", "content": "A retrospective review of 375 consecutive orthotopic liver transplants was performed to determine the incidence and outcome of late rejection episodes ([LR] rejection occurring more than 6 months following transplant). A total of 31 episodes in 26 patients were identified. Eighteen of these episodes were associated with subtherapeutic levels of cyclosporine. Of these, 7 were due to noncompliance, 2 were due to biliary strictures, and 1 was due to malabsorption in a cystic fibrosis patient. All 31 episodes were treated initially with steroids, and 22 had a complete response, although one progressed to chronic rejection over a year later. Of the remaining 9, 1 received FK506 with a complete response, and 8 received OKT3. Of the 8 patients who received OKT3, 5 had a complete response, 1 received RS61443 following OKT3 and progressed to chronic rejection, and the remaining 2 received further steroids. Of these 2, 1 had a complete response following the steroids while the second was converted to FK506 with a complete response. Compared with 315 acute rejection episodes ([AR] occurring less than 6 months posttransplant), patients with late rejection episodes had an equivalent response to steroids (63.2% AR reversed vs. 71% LR reversed) but a lower response rate to OKT3 (91.5% AR reversed vs. 62.5% LR reversed). There was, therefore, a higher rate of persistent rejection (61% AR episodes vs. 15.4% LR episodes) but no increase in the incidence of chronic rejection (7% AR episodes vs. 7.7% LR episodes). We conclude that LR is a relatively common occurrence following liver transplant, which is most often associated with low cyclosporine levels. Many of these episodes are due to noncompliance, but biliary problems must also be investigated. The incidence of resistant rejection is higher in this group of patients but is not associated with a concurrent increase in chronic rejection.", "contents": "Late-onset acute rejection in orthotopic liver transplantation--associated risk factors and outcome. A retrospective review of 375 consecutive orthotopic liver transplants was performed to determine the incidence and outcome of late rejection episodes ([LR] rejection occurring more than 6 months following transplant). A total of 31 episodes in 26 patients were identified. Eighteen of these episodes were associated with subtherapeutic levels of cyclosporine. Of these, 7 were due to noncompliance, 2 were due to biliary strictures, and 1 was due to malabsorption in a cystic fibrosis patient. All 31 episodes were treated initially with steroids, and 22 had a complete response, although one progressed to chronic rejection over a year later. Of the remaining 9, 1 received FK506 with a complete response, and 8 received OKT3. Of the 8 patients who received OKT3, 5 had a complete response, 1 received RS61443 following OKT3 and progressed to chronic rejection, and the remaining 2 received further steroids. Of these 2, 1 had a complete response following the steroids while the second was converted to FK506 with a complete response. Compared with 315 acute rejection episodes ([AR] occurring less than 6 months posttransplant), patients with late rejection episodes had an equivalent response to steroids (63.2% AR reversed vs. 71% LR reversed) but a lower response rate to OKT3 (91.5% AR reversed vs. 62.5% LR reversed). There was, therefore, a higher rate of persistent rejection (61% AR episodes vs. 15.4% LR episodes) but no increase in the incidence of chronic rejection (7% AR episodes vs. 7.7% LR episodes). We conclude that LR is a relatively common occurrence following liver transplant, which is most often associated with low cyclosporine levels. Many of these episodes are due to noncompliance, but biliary problems must also be investigated. The incidence of resistant rejection is higher in this group of patients but is not associated with a concurrent increase in chronic rejection."} {"id": "PMID:1279847", "title": "An optimal rice-based oral rehydration solution: the effect of different concentrations of amylase on production of short chain polymers of glucose.", "content": "As part of a plan to develop a rice-based oral rehydration solution containing short polymers of glucose instead of glucose, we determined the concentration of amylase that would yield the largest amount of short chain polymers. Thai rice (25 g) was boiled with 500 ml of distilled water for 30 min. Of 200 ml supernatant rice water obtained, 100 ml were digested with different amounts of amylase after cooling to 50 degrees C for 60 min, boiled for 5 min, and centrifuged (10,000 g, 25 degrees C) for 60 min. The resulting supernatant (80 ml) was freeze-dried; 1.75 g of the powder obtained were dissolved in 3.5 ml of water, passed through a Bio-Gel P2 column to separate short chain polymers (2-9 molecules of glucose) and long chain polymers (> 9 molecules of glucose), which were identified by spectrophotometry (lambda = 190 nm) or by high performance liquid chromatography. Ten mg of amylase (equivalent to 12,000 modified Wohlgemath units) per 100 ml of rice water was optimal for the production of short polymers of glucose from rice.", "contents": "An optimal rice-based oral rehydration solution: the effect of different concentrations of amylase on production of short chain polymers of glucose. As part of a plan to develop a rice-based oral rehydration solution containing short polymers of glucose instead of glucose, we determined the concentration of amylase that would yield the largest amount of short chain polymers. Thai rice (25 g) was boiled with 500 ml of distilled water for 30 min. Of 200 ml supernatant rice water obtained, 100 ml were digested with different amounts of amylase after cooling to 50 degrees C for 60 min, boiled for 5 min, and centrifuged (10,000 g, 25 degrees C) for 60 min. The resulting supernatant (80 ml) was freeze-dried; 1.75 g of the powder obtained were dissolved in 3.5 ml of water, passed through a Bio-Gel P2 column to separate short chain polymers (2-9 molecules of glucose) and long chain polymers (> 9 molecules of glucose), which were identified by spectrophotometry (lambda = 190 nm) or by high performance liquid chromatography. Ten mg of amylase (equivalent to 12,000 modified Wohlgemath units) per 100 ml of rice water was optimal for the production of short polymers of glucose from rice."} {"id": "PMID:1279850", "title": "The effects of FK506 and cyclosporine on the exocrine function of the rat pancreas.", "content": "The effects of FK506 on exocrine function of the pancreas in Sprague-Dawley rats were examined and compared with those of cyclosporine. FK506 did not affect the levels of amylase and lipase in the pancreas of rats given the drug orally in a daily dose of 1 or 5 mg/kg for 2 weeks. Furthermore, the pancreas of the rats showed good exocrine secretion of enzymes such as amylase and lipase on stimulation with carbachol in vitro. Cyclosporine 50 mg/kg given in the same way as FK506 also was free of effect on enzyme levels in the rat pancreas, but the exocrine secretion of the enzyme from the pancreatic lobules on stimulation with carbachol was impaired. It is concluded that FK506 does not affect pancreatic exocrine function in rats.", "contents": "The effects of FK506 and cyclosporine on the exocrine function of the rat pancreas. The effects of FK506 on exocrine function of the pancreas in Sprague-Dawley rats were examined and compared with those of cyclosporine. FK506 did not affect the levels of amylase and lipase in the pancreas of rats given the drug orally in a daily dose of 1 or 5 mg/kg for 2 weeks. Furthermore, the pancreas of the rats showed good exocrine secretion of enzymes such as amylase and lipase on stimulation with carbachol in vitro. Cyclosporine 50 mg/kg given in the same way as FK506 also was free of effect on enzyme levels in the rat pancreas, but the exocrine secretion of the enzyme from the pancreatic lobules on stimulation with carbachol was impaired. It is concluded that FK506 does not affect pancreatic exocrine function in rats."} {"id": "PMID:1279852", "title": "The spectrum of cystic fibrosis mutations.", "content": "Although the major mutation causing cystic fibrosis accounts for almost 70% of mutant chromosomes screened, almost 300 sequence alterations have been identified in the gene during the past two and a half years. At least 230 of these mutations are probably associated with disease. This rapid accumulation of data is in part due to the highly coordinated effort by members of the Cystic Fibrosis Genetic Analysis Consortium. The information is not only essential to genetic diagnosis, but also will aid in understanding the structure and function of the protein, and possibly in correlating genotype with phenotype.", "contents": "The spectrum of cystic fibrosis mutations. Although the major mutation causing cystic fibrosis accounts for almost 70% of mutant chromosomes screened, almost 300 sequence alterations have been identified in the gene during the past two and a half years. At least 230 of these mutations are probably associated with disease. This rapid accumulation of data is in part due to the highly coordinated effort by members of the Cystic Fibrosis Genetic Analysis Consortium. The information is not only essential to genetic diagnosis, but also will aid in understanding the structure and function of the protein, and possibly in correlating genotype with phenotype."} {"id": "PMID:1279855", "title": "Iterated patterns of brain circuitry (or how the cortex gets its spots)", "content": "The prominence of repeating patterns of circuitry in the mammalian brain has led to the general view that iterated modular units reflect a fundamental principle of cortical function. Here we argue that these intriguing patterns arise not because the functional organization of the brain demands them, but as an incidental consequence of the rules of synapse formation.", "contents": "Iterated patterns of brain circuitry (or how the cortex gets its spots). The prominence of repeating patterns of circuitry in the mammalian brain has led to the general view that iterated modular units reflect a fundamental principle of cortical function. Here we argue that these intriguing patterns arise not because the functional organization of the brain demands them, but as an incidental consequence of the rules of synapse formation."} {"id": "PMID:1279856", "title": "Lineage versus environment in embryonic retina: a revisionist perspective.", "content": "The idea that microenvironmental cues act alone late in development to determine a cell's phenotype has dominated recent discussion of, retinal development, and has successfully displaced the notion of any role for cell lineage in the process of cell determination. We argue that there is, in fact, evidence favoring a degree of lineage restriction during the development of the vertebrate retina. We propose that environmental factors modulate a process of progressive lineage restriction. In this model, progenitor cells are viewed as having unequal potential, and their progeny are viewed as being committed to one of the major retinal cell classes before the stage at which they become postmitotic.", "contents": "Lineage versus environment in embryonic retina: a revisionist perspective. The idea that microenvironmental cues act alone late in development to determine a cell's phenotype has dominated recent discussion of, retinal development, and has successfully displaced the notion of any role for cell lineage in the process of cell determination. We argue that there is, in fact, evidence favoring a degree of lineage restriction during the development of the vertebrate retina. We propose that environmental factors modulate a process of progressive lineage restriction. In this model, progenitor cells are viewed as having unequal potential, and their progeny are viewed as being committed to one of the major retinal cell classes before the stage at which they become postmitotic."} {"id": "PMID:1279857", "title": "Visceral nociceptors: a new world order?", "content": "There has been a long-standing controversy as to whether or not internal organs are innervated by a special category of 'visceral nociceptor'. Recent experimental studies on the afferent supply of some viscera have thrown new light on this issue by demonstrating the presence of several categories of visceral sensory receptor, including high-threshold receptors, 'silent' nociceptors and intensity-encoding receptors. Advances in the understanding of how the CNS processes nociceptive signals have also helped to clarify the issue. The authors of this report, originally having different points of view, present here a common and closer approach to the visceral nociceptor controversy.", "contents": "Visceral nociceptors: a new world order? There has been a long-standing controversy as to whether or not internal organs are innervated by a special category of 'visceral nociceptor'. Recent experimental studies on the afferent supply of some viscera have thrown new light on this issue by demonstrating the presence of several categories of visceral sensory receptor, including high-threshold receptors, 'silent' nociceptors and intensity-encoding receptors. Advances in the understanding of how the CNS processes nociceptive signals have also helped to clarify the issue. The authors of this report, originally having different points of view, present here a common and closer approach to the visceral nociceptor controversy."} {"id": "PMID:1279858", "title": "Neuroscience training in the USA and Canada: observations and suggestions.", "content": "Neuroscience training programs in the USA and Canada are awarding about 1000 PhDs each year. This number exceeds the faculty vacancies in these programs by a ratio of three to one. Nonetheless, virtually all graduates are finding employment, usually after a period of postdoctoral experience. On the other hand, recent surveys suggest that there are many other concerns to be addressed. These include an attrition of women during training and within the faculty ranks, a low percentage of minorities throughout the neuroscience community, and a relative lack of federal training funds.", "contents": "Neuroscience training in the USA and Canada: observations and suggestions. Neuroscience training programs in the USA and Canada are awarding about 1000 PhDs each year. This number exceeds the faculty vacancies in these programs by a ratio of three to one. Nonetheless, virtually all graduates are finding employment, usually after a period of postdoctoral experience. On the other hand, recent surveys suggest that there are many other concerns to be addressed. These include an attrition of women during training and within the faculty ranks, a low percentage of minorities throughout the neuroscience community, and a relative lack of federal training funds."} {"id": "PMID:1279859", "title": "Training neuroscientists for the 21st century.", "content": "Maintaining the highest possible level of talented researchers relies critically on the ability to recruit, train and retain the best young students to the neurosciences. This article addresses the need for trainers to look beyond technical skills, on which research training conventionally concentrates, to some para-scientific skills that may help assure survival during the apparently perennial periods of scarce resources.", "contents": "Training neuroscientists for the 21st century. Maintaining the highest possible level of talented researchers relies critically on the ability to recruit, train and retain the best young students to the neurosciences. This article addresses the need for trainers to look beyond technical skills, on which research training conventionally concentrates, to some para-scientific skills that may help assure survival during the apparently perennial periods of scarce resources."} {"id": "PMID:1279864", "title": "Sulfated glycoprotein 2: new relationships of this multifunctional protein to neurodegeneration.", "content": "Sulfated glycoprotein 2 (SGP-2) from rat, and similar molecules from cow, dog, human, pig, ram and quail are known by 11 or more acronyms. SGP-2 is associated with the responses of brain and other tissues to injury; it and related molecules are also normally secreted by the adrenal gland, the liver and the testes. The mRNA of this protein is found in increased levels in Alzheimer's disease. In rats, after perforant path or excitotoxin lesions, levels of the protein or mRNA are elevated in astrocytes, and also in neurons. In rats, brain SGP-2 is regulated by gonadal and adrenal steroids. However, these increases after brain lesions may relate to a function that is associated with the human protein, namely that of inhibiting complement-mediated cell lysis. Other activities suggested for SGP-2 are lipid transport and cell-cell interactions, which are consistent with sequence data that predict binding of dinucleotides, heparin and lipids. The emerging neurobiology of SGP-2 encompasses the subjects of cell death, synaptic remodelling, neuroendocrinology and neurodegenerative diseases.", "contents": "Sulfated glycoprotein 2: new relationships of this multifunctional protein to neurodegeneration. Sulfated glycoprotein 2 (SGP-2) from rat, and similar molecules from cow, dog, human, pig, ram and quail are known by 11 or more acronyms. SGP-2 is associated with the responses of brain and other tissues to injury; it and related molecules are also normally secreted by the adrenal gland, the liver and the testes. The mRNA of this protein is found in increased levels in Alzheimer's disease. In rats, after perforant path or excitotoxin lesions, levels of the protein or mRNA are elevated in astrocytes, and also in neurons. In rats, brain SGP-2 is regulated by gonadal and adrenal steroids. However, these increases after brain lesions may relate to a function that is associated with the human protein, namely that of inhibiting complement-mediated cell lysis. Other activities suggested for SGP-2 are lipid transport and cell-cell interactions, which are consistent with sequence data that predict binding of dinucleotides, heparin and lipids. The emerging neurobiology of SGP-2 encompasses the subjects of cell death, synaptic remodelling, neuroendocrinology and neurodegenerative diseases."} {"id": "PMID:1279865", "title": "Modulation of pH by neuronal activity.", "content": "Although the requirement for a strict regulation of pH in the brain is frequently emphasized, recent studies indicate that neuronal activity gives rise to significant changes in intracellular and extracellular pH. Given the sensitivity of many ion channels to hydrogen ions, this modulation of local pH might influence brain function, particularly where pH shifts are sufficiently large and rapid. Studies using pH-sensitive microelectrodes have demonstrated marked cellular and regional variability of activity-dependent pH shifts, and have begun to uncover several of their underlying mechanisms. Accumulating evidence suggests that regional and subcellular pH dynamics are governed by the respective localization of glial cells, ligand-gated ion channels, and extracellular and intracellular carbonic anhydrase.", "contents": "Modulation of pH by neuronal activity. Although the requirement for a strict regulation of pH in the brain is frequently emphasized, recent studies indicate that neuronal activity gives rise to significant changes in intracellular and extracellular pH. Given the sensitivity of many ion channels to hydrogen ions, this modulation of local pH might influence brain function, particularly where pH shifts are sufficiently large and rapid. Studies using pH-sensitive microelectrodes have demonstrated marked cellular and regional variability of activity-dependent pH shifts, and have begun to uncover several of their underlying mechanisms. Accumulating evidence suggests that regional and subcellular pH dynamics are governed by the respective localization of glial cells, ligand-gated ion channels, and extracellular and intracellular carbonic anhydrase."} {"id": "PMID:1279866", "title": "An enzymatic mechanism for potassium channel stimulation through pertussis-toxin-sensitive G proteins.", "content": "Many neurotransmitters inhibit secretion from electrically excitable cells by activating pertussis-toxin-sensitive G proteins that modulate voltage-gated ion channels. Recent electrophysiological studies of metabolically intact cells from mammalian and molluscan neuroendocrine systems have implicated protein phosphatases in this process. In this article David Armstrong and Richard White review these studies and suggest a biochemical pathway that might link one of the G proteins to protein phosphatase activity.", "contents": "An enzymatic mechanism for potassium channel stimulation through pertussis-toxin-sensitive G proteins. Many neurotransmitters inhibit secretion from electrically excitable cells by activating pertussis-toxin-sensitive G proteins that modulate voltage-gated ion channels. Recent electrophysiological studies of metabolically intact cells from mammalian and molluscan neuroendocrine systems have implicated protein phosphatases in this process. In this article David Armstrong and Richard White review these studies and suggest a biochemical pathway that might link one of the G proteins to protein phosphatase activity."} {"id": "PMID:1279867", "title": "Membrane ion channels of endothelial cells.", "content": "It is becoming clear that endothelial cells in the vascular system have important functions. In the microvessels they play an active role in regulating vascular permeability, while in large vessels, endothelial cells contribute to the control of smooth muscle tone. Control of both permeability and tone involve a range of mechanisms, in which changes in [Ca2+]i appear to play a major role. As elevation of [Ca2+]i can be caused by either release from intracellular stores or increased entry across the plasmalemma, and as the latter will be modulated by the resting membrane potential, the ion channels controlling the membrane potential are critical to an understanding of endothelial function. Patricia Revest and Joan Abbott summarize the properties of endothelial ion channels, and explore the ways in which the channels could control permeability, secretion and smooth muscle tone.", "contents": "Membrane ion channels of endothelial cells. It is becoming clear that endothelial cells in the vascular system have important functions. In the microvessels they play an active role in regulating vascular permeability, while in large vessels, endothelial cells contribute to the control of smooth muscle tone. Control of both permeability and tone involve a range of mechanisms, in which changes in [Ca2+]i appear to play a major role. As elevation of [Ca2+]i can be caused by either release from intracellular stores or increased entry across the plasmalemma, and as the latter will be modulated by the resting membrane potential, the ion channels controlling the membrane potential are critical to an understanding of endothelial function. Patricia Revest and Joan Abbott summarize the properties of endothelial ion channels, and explore the ways in which the channels could control permeability, secretion and smooth muscle tone."} {"id": "PMID:1279868", "title": "[Programs of mass and selective screening of pregnant women in prenatal studies. Screening of alpha fetoprotein in the blood serum of the mother].", "content": "The total of 38479 echography studies and 25147 alpha-fetoprotein estimations in mother blood serum have been performed upon prenatal screening. 445 congenital developmental defects are revealed. AFP base and limiting values (2.5 MoM and 0.5 MoM) are found. AFP values and echocardiography results in the nor and in genetic syndromes of multiple congenital developmental defects are compared. It is found that AFP values are higher than MoM or only slightly higher than Me in the same syndromes. The different level of AFP for the same syndromes appeared to be associated with the phenomenon of overlapping due to the clinical polymorphism and type of injury of the nervous system and with the extent of changes in placenta, amniotic fluid and umbilical cord were revealed in 99% of syndromes. The increased AFP level can be considered as a marker to detect signs of the genetic syndromes. Low AFP level peculiar to aneuploidy appeared to be normal or increased. The AFP test can be used as a marker of changed embryogenesis.", "contents": "[Programs of mass and selective screening of pregnant women in prenatal studies. Screening of alpha fetoprotein in the blood serum of the mother]. The total of 38479 echography studies and 25147 alpha-fetoprotein estimations in mother blood serum have been performed upon prenatal screening. 445 congenital developmental defects are revealed. AFP base and limiting values (2.5 MoM and 0.5 MoM) are found. AFP values and echocardiography results in the nor and in genetic syndromes of multiple congenital developmental defects are compared. It is found that AFP values are higher than MoM or only slightly higher than Me in the same syndromes. The different level of AFP for the same syndromes appeared to be associated with the phenomenon of overlapping due to the clinical polymorphism and type of injury of the nervous system and with the extent of changes in placenta, amniotic fluid and umbilical cord were revealed in 99% of syndromes. The increased AFP level can be considered as a marker to detect signs of the genetic syndromes. Low AFP level peculiar to aneuploidy appeared to be normal or increased. The AFP test can be used as a marker of changed embryogenesis."} {"id": "PMID:1279869", "title": "[Possibilities and prospects of the use of DNA analysis in the diagnosis and prevention of inherited disease in the Ukraine].", "content": "The results from molecular genetic analysis of some mutations in the 10th and 11th exons of cystic fibrosis transmembrane regulator (CFTR) gene as well as of deletions in the 8, 17, 19, 43, 50, 60th exons of dystrophin gene in 61 CF-families and 21 DMD-families from different Ukraine regions are presented. It was shown that delta F508 frequency of CF-patients was 59.2%, the frequencies of S5491, G551D and K533X were about 1%. The frequency of delta F508-carriers analysed among 365 healthy donors from different regions of Ukraine was 1:40. The analyzed deletions of dystrophin gene were revealed only among 6 DMD-patients. The associations of analyzed mutations of CFTR gene and DMD-gene with RELP's in 4 loci of chromosome 7 and 2 loci of X-chromosome, respectively, were found. The results of prenatal diagnosis of cystic fibrosis and DMD are presented.", "contents": "[Possibilities and prospects of the use of DNA analysis in the diagnosis and prevention of inherited disease in the Ukraine]. The results from molecular genetic analysis of some mutations in the 10th and 11th exons of cystic fibrosis transmembrane regulator (CFTR) gene as well as of deletions in the 8, 17, 19, 43, 50, 60th exons of dystrophin gene in 61 CF-families and 21 DMD-families from different Ukraine regions are presented. It was shown that delta F508 frequency of CF-patients was 59.2%, the frequencies of S5491, G551D and K533X were about 1%. The frequency of delta F508-carriers analysed among 365 healthy donors from different regions of Ukraine was 1:40. The analyzed deletions of dystrophin gene were revealed only among 6 DMD-patients. The associations of analyzed mutations of CFTR gene and DMD-gene with RELP's in 4 loci of chromosome 7 and 2 loci of X-chromosome, respectively, were found. The results of prenatal diagnosis of cystic fibrosis and DMD are presented."} {"id": "PMID:1279872", "title": "In vitro investigations on cellular damage induced by high energy shock waves.", "content": "Single-cell suspensions of the prostate carcinoma cell line PCA were exposed to electromagnetically generated ultrasound shock waves (source and focusing lens identical to those used in the commercially available lithotripor Lithostar Plus). Cell loss of up to 40% occurred in sample tubes containing air. To expose multicellular tumor spheroids and cells growing on a microcarrier, an experimental setup was developed that prevented motion of the specimen. Intracellular damage of intact spheroids was analyzed by laser scanning microscopy following specific fluorescence staining. Different sensitivities of individual cell components with respect to the applied energy density of the pulses were found, namely defects on cell membranes (0.12 mJ/mm2), vimentin (0.21 mJ/mm2), mitochondria (0.33 mJ/mm2) and nuclear membranes (0.5 mJ/mm2). Loss of cells growing on a microcarrier was found after application of 200 pulses with 0.21 mJ/mm2.", "contents": "In vitro investigations on cellular damage induced by high energy shock waves. Single-cell suspensions of the prostate carcinoma cell line PCA were exposed to electromagnetically generated ultrasound shock waves (source and focusing lens identical to those used in the commercially available lithotripor Lithostar Plus). Cell loss of up to 40% occurred in sample tubes containing air. To expose multicellular tumor spheroids and cells growing on a microcarrier, an experimental setup was developed that prevented motion of the specimen. Intracellular damage of intact spheroids was analyzed by laser scanning microscopy following specific fluorescence staining. Different sensitivities of individual cell components with respect to the applied energy density of the pulses were found, namely defects on cell membranes (0.12 mJ/mm2), vimentin (0.21 mJ/mm2), mitochondria (0.33 mJ/mm2) and nuclear membranes (0.5 mJ/mm2). Loss of cells growing on a microcarrier was found after application of 200 pulses with 0.21 mJ/mm2."} {"id": "PMID:1279870", "title": "Immunogold localization of actin and cytokeratin filaments in myoepithelium of human parotid salivary gland.", "content": "Myoepithelial cells of salivary gland are uniquely specialized cells; their function is unclear, but the considerable complement of muscle-specific actin suggests contractility is one function. By routine transmission electron microscopy myofilament visualization is variable. Some myoepithelial cells appear to have limited and only focal aggregates of myofilaments, while others seem to have readily appreciated myofilaments within a longitudinally oriented cytoplasmic zone at the basal portion of the cell. However, immunogold electron microscopy using the anti-muscle-specific actin antibody, HHF35, while indicating a basal distribution for the muscle-isoform of actin in a platelike fashion in certain myoepithelial cells, also reveals that others associated with both intercalated ducts and acini have a more generalized distribution of myofilaments throughout the cytoplasm. Actin was also noted within tonofilaments and double immunogold labeling using both the HHF35 and AE1/AE3 (anticytokeratins) antibodies confirmed the variable interrelationship of these two filaments. Within any one myoepithelial cell, actin and cytokeratins might colocalize in some areas of the cytoplasm containing filaments, but not in adjacent zones. These results suggest that intermediate filaments and myofilaments are complexly organized in myoepithelial cells, and that quantitative and qualitative differences exist in the expression and distribution of intermediate filaments and myofilaments. These cells are likely structurally, if not functionally, heterogeneous.", "contents": "Immunogold localization of actin and cytokeratin filaments in myoepithelium of human parotid salivary gland. Myoepithelial cells of salivary gland are uniquely specialized cells; their function is unclear, but the considerable complement of muscle-specific actin suggests contractility is one function. By routine transmission electron microscopy myofilament visualization is variable. Some myoepithelial cells appear to have limited and only focal aggregates of myofilaments, while others seem to have readily appreciated myofilaments within a longitudinally oriented cytoplasmic zone at the basal portion of the cell. However, immunogold electron microscopy using the anti-muscle-specific actin antibody, HHF35, while indicating a basal distribution for the muscle-isoform of actin in a platelike fashion in certain myoepithelial cells, also reveals that others associated with both intercalated ducts and acini have a more generalized distribution of myofilaments throughout the cytoplasm. Actin was also noted within tonofilaments and double immunogold labeling using both the HHF35 and AE1/AE3 (anticytokeratins) antibodies confirmed the variable interrelationship of these two filaments. Within any one myoepithelial cell, actin and cytokeratins might colocalize in some areas of the cytoplasm containing filaments, but not in adjacent zones. These results suggest that intermediate filaments and myofilaments are complexly organized in myoepithelial cells, and that quantitative and qualitative differences exist in the expression and distribution of intermediate filaments and myofilaments. These cells are likely structurally, if not functionally, heterogeneous."} {"id": "PMID:1279873", "title": "[Technical recommendation for connecting osteosynthesis].", "content": "In patients with pathological fractures an operative stabilisation is indicated without delay although 40 to 50% of the patients survive only three to four months. Generally palliative operations are practiced. Mostly a connecting osteosynthesis is carried out in which after resection of the tumorous bone the stability can be achieved by the application of plates and filling of the bone defect with cement. In three examplary cases a technical improvement of the impaction of bone cement is described. Using an exactly cutted packing ring of a single use syringe after the application of the plate the bone cement can be filled in easily. By the casting a penetration of the bone cement into the soft tissues can be avoided. An additional effect is that pins of cement extend into the bone narrow with a sufficient support of the filling on the cortical bone. After the removal of the casting the screws can be inserted in the overbridged defect while the polymerisation has nearly finished.", "contents": "[Technical recommendation for connecting osteosynthesis]. In patients with pathological fractures an operative stabilisation is indicated without delay although 40 to 50% of the patients survive only three to four months. Generally palliative operations are practiced. Mostly a connecting osteosynthesis is carried out in which after resection of the tumorous bone the stability can be achieved by the application of plates and filling of the bone defect with cement. In three examplary cases a technical improvement of the impaction of bone cement is described. Using an exactly cutted packing ring of a single use syringe after the application of the plate the bone cement can be filled in easily. By the casting a penetration of the bone cement into the soft tissues can be avoided. An additional effect is that pins of cement extend into the bone narrow with a sufficient support of the filling on the cortical bone. After the removal of the casting the screws can be inserted in the overbridged defect while the polymerisation has nearly finished."} {"id": "PMID:1279871", "title": "Use of combined myeloperoxidase and immunogold technique in hybrid leukemia: a case report.", "content": "A case of hybrid leukemia is presented. A 30-year-old man had two blast cell populations with bone marrow. The majority of the blast cells had B-lymphoid markers on their surfaces and a small number of cells had both lymphoid markers and penoxidase activity on the same cell. Immunoelectron microscopy combined with ultrastructural cytochemistry (MPO reaction) demonstrated the biphenotypic nature of the blast cells.", "contents": "Use of combined myeloperoxidase and immunogold technique in hybrid leukemia: a case report. A case of hybrid leukemia is presented. A 30-year-old man had two blast cell populations with bone marrow. The majority of the blast cells had B-lymphoid markers on their surfaces and a small number of cells had both lymphoid markers and penoxidase activity on the same cell. Immunoelectron microscopy combined with ultrastructural cytochemistry (MPO reaction) demonstrated the biphenotypic nature of the blast cells."} {"id": "PMID:1279876", "title": "Radical cystectomy in regionally advanced bladder cancer.", "content": "The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients.", "contents": "Radical cystectomy in regionally advanced bladder cancer. The distinction pathologically of invasive tumors confined to the muscularis propria from those that penetrate the bladder wall and invade the perivesical fat or adjacent organs is a critical prognostic determinant. Nodal metastases are evident in approximately one half of patients with tumors pathologically staged as P3b or greater. Five-year survival rates after radical cystectomy with or without preoperative irradiation for stage P3b tumors range from 17% to 46%. Long-term survival is the exception when bladder cancer invades the pelvic sidewall or adjacent structures, yet cystectomy can provide palliation and accurate staging and can be considered in the context of combination therapy. Supravesical diversion can provide palliation when there is nodal disease above the bifurcation or pelvic fixation. The optimal role of adjuvant chemotherapy in the treatment of regionally advanced bladder cancer is yet to be defined. Tannock has delineated the many serious pitfalls inherent in interpreting nonrandomized trials of new therapies (see also his article elsewhere in this issue). Randomized trials are currently under way to determine if survival can be improved with adjuvant or neoadjuvant chemotherapy and the most efficacious timing of chemotherapy administration. Clinicians should generally resist the tendency to treat all patients with these regimens until it is clear that we are truly improving the outcome of therapy and the quality of life for our patients."} {"id": "PMID:1279877", "title": "Metastatic bladder cancer. Natural history, clinical course, and consideration for treatment.", "content": "Patients with metastatic transitional-cell carcinoma of the bladder have a poor prognosis with brief survival. Controversy exists as to the clonality of bladder cancer, as well as the natural history of muscle-invasive disease that subsequently becomes metastatic. Newer molecular biologic techniques may help us identify and understand the molecular changes involved in transforming normal urothelium into the malignant phenotype. In addition, newer chromosomal markers may enable us to determine the prognosis and the potential for progression to invasion and metastases. Additional work to find the optimum doses and dosing schedules and combinations of chemotherapeutic agents for metastatic transitional-cell carcinoma will be necessary before we can improve survival for all patients with this disease.", "contents": "Metastatic bladder cancer. Natural history, clinical course, and consideration for treatment. Patients with metastatic transitional-cell carcinoma of the bladder have a poor prognosis with brief survival. Controversy exists as to the clonality of bladder cancer, as well as the natural history of muscle-invasive disease that subsequently becomes metastatic. Newer molecular biologic techniques may help us identify and understand the molecular changes involved in transforming normal urothelium into the malignant phenotype. In addition, newer chromosomal markers may enable us to determine the prognosis and the potential for progression to invasion and metastases. Additional work to find the optimum doses and dosing schedules and combinations of chemotherapeutic agents for metastatic transitional-cell carcinoma will be necessary before we can improve survival for all patients with this disease."} {"id": "PMID:1279878", "title": "Is open prostatectomy really obsolete?", "content": "A total of 1,066 prostatectomies treated by us from 1985 to 1989 were reviewed. The necessary comprehensive data were available on 710 cases. Open (Millin's retropubic) prostatectomy (RPP) was the procedure of choice for large glands and transurethral resection (TURP) for smaller glands: 408 had had RPP and 262 TURP; 14.5 percent of the TURP group eventually needed a second procedure during a one to six-year follow-up compared with only 2.6 percent of the RPP group. Forty other patients who had been operated on elsewhere were referred to us for a second, repeat procedure; 30 also previously had had a TURP. Total hospitalization, operating time, and complications were better in the long run in the RPP group compared with the TURP group. It is believed that open prostatectomy still has a respectable place in urology and therefore, should be considered and also taught to residents for use in dealing with large glands.", "contents": "Is open prostatectomy really obsolete? A total of 1,066 prostatectomies treated by us from 1985 to 1989 were reviewed. The necessary comprehensive data were available on 710 cases. Open (Millin's retropubic) prostatectomy (RPP) was the procedure of choice for large glands and transurethral resection (TURP) for smaller glands: 408 had had RPP and 262 TURP; 14.5 percent of the TURP group eventually needed a second procedure during a one to six-year follow-up compared with only 2.6 percent of the RPP group. Forty other patients who had been operated on elsewhere were referred to us for a second, repeat procedure; 30 also previously had had a TURP. Total hospitalization, operating time, and complications were better in the long run in the RPP group compared with the TURP group. It is believed that open prostatectomy still has a respectable place in urology and therefore, should be considered and also taught to residents for use in dealing with large glands."} {"id": "PMID:1279879", "title": "Malignant schwannoma of kidney capsule.", "content": "This report is of a malignant schwannoma originating in the capsule of the right kidney. Using sonography, nephroangiography, cavography, computer tomography, and bone scanning, metastases in the kidney or a retroperitoneal tumor could be diagnosed. After transperitoneal exploration, the right kidney and mesenteric metastases were removed. Due to tumor infiltration into the liver and tumor masses in the retroperitoneum, only nephrectomy and palliative excision of retroperitoneal metastases were done. Pulmonary metastases developed postoperatively, and the patient died three months after the operation.", "contents": "Malignant schwannoma of kidney capsule. This report is of a malignant schwannoma originating in the capsule of the right kidney. Using sonography, nephroangiography, cavography, computer tomography, and bone scanning, metastases in the kidney or a retroperitoneal tumor could be diagnosed. After transperitoneal exploration, the right kidney and mesenteric metastases were removed. Due to tumor infiltration into the liver and tumor masses in the retroperitoneum, only nephrectomy and palliative excision of retroperitoneal metastases were done. Pulmonary metastases developed postoperatively, and the patient died three months after the operation."} {"id": "PMID:1279875", "title": "[Antiviral strategies in the replication of human immunodeficiency virus].", "content": "The replication cycle of any virus involves a number of steps, beginning with specific attachment to a cell surface receptor leading eventually to production of progeny viruses by infected cells. In the case of the immunodeficiency virus type-1 (HIV-1), the first step involves a specific interaction between the gp120 viral envelope surface protein and specific CD4 receptor sites at the cell surface. This is followed by penetration of the virus into cells and the formation of proviral double-stranded DNA from single-stranded viral RNA, a process mediated through the action of the viral enzyme called reverse transcriptase. This, in turn, leads to the migration of proviral DNA into the nucleus of the cell and the integration of such DNA within the host cell genome. Finally both viral RNA and viral proteins are produced by the cell's genetic apparatus and new viruses are assembled at the cell surface. The fact that integration of viral DNA into host cell chromosomes occurs means that any cellular replication event will be accompanied by replication of viral DNA. Each of these steps represents a potential target for anti-viral chemotherapy. To date, most efforts to treat HIV-associated disease have focused on the reverse transcription step. In this respect, zidovudine (AZT) has been the most widely used anti-viral drug studied. However, the relative toxicity and lack of efficiency of this drug means that our efforts to develop new therapeutic strategies to combat HIV infection must continue.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Antiviral strategies in the replication of human immunodeficiency virus]. The replication cycle of any virus involves a number of steps, beginning with specific attachment to a cell surface receptor leading eventually to production of progeny viruses by infected cells. In the case of the immunodeficiency virus type-1 (HIV-1), the first step involves a specific interaction between the gp120 viral envelope surface protein and specific CD4 receptor sites at the cell surface. This is followed by penetration of the virus into cells and the formation of proviral double-stranded DNA from single-stranded viral RNA, a process mediated through the action of the viral enzyme called reverse transcriptase. This, in turn, leads to the migration of proviral DNA into the nucleus of the cell and the integration of such DNA within the host cell genome. Finally both viral RNA and viral proteins are produced by the cell's genetic apparatus and new viruses are assembled at the cell surface. The fact that integration of viral DNA into host cell chromosomes occurs means that any cellular replication event will be accompanied by replication of viral DNA. Each of these steps represents a potential target for anti-viral chemotherapy. To date, most efforts to treat HIV-associated disease have focused on the reverse transcription step. In this respect, zidovudine (AZT) has been the most widely used anti-viral drug studied. However, the relative toxicity and lack of efficiency of this drug means that our efforts to develop new therapeutic strategies to combat HIV infection must continue.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279882", "title": "An outbreak of melioidosis in imported primates in Britain.", "content": "An outbreak of melioidosis, a bacterial infection caused by Pseudomonas pseudomallei, was identified in a batch of feral cynomolgus monkeys (Macaca fascicularis) imported to Britain from the Philippines. Thirteen confirmed or possible cases occurred among a batch of 50 animals. Subsequent investigations revealed that the infection was uncommon among imported primates from a variety of sources, although three other cases were identified in monkeys imported from Indonesia. The majority of the affected monkeys had splenic abscesses, and hepatic abscesses and infections of the soft tissues and skin were also frequently observed. Most of the infected animals had no clinical signs despite extensive abscesses, and the presence of infection was only suspected when they were shown to have serum antibodies to P pseudomallei by an enzyme-linked immunosorbent assay. Although there was no evidence of cross infection of other animals or human handlers, this outbreak is a reminder of the dangers of working with wild-caught primates and the potential for the establishment of environmental foci of melioidosis.", "contents": "An outbreak of melioidosis in imported primates in Britain. An outbreak of melioidosis, a bacterial infection caused by Pseudomonas pseudomallei, was identified in a batch of feral cynomolgus monkeys (Macaca fascicularis) imported to Britain from the Philippines. Thirteen confirmed or possible cases occurred among a batch of 50 animals. Subsequent investigations revealed that the infection was uncommon among imported primates from a variety of sources, although three other cases were identified in monkeys imported from Indonesia. The majority of the affected monkeys had splenic abscesses, and hepatic abscesses and infections of the soft tissues and skin were also frequently observed. Most of the infected animals had no clinical signs despite extensive abscesses, and the presence of infection was only suspected when they were shown to have serum antibodies to P pseudomallei by an enzyme-linked immunosorbent assay. Although there was no evidence of cross infection of other animals or human handlers, this outbreak is a reminder of the dangers of working with wild-caught primates and the potential for the establishment of environmental foci of melioidosis."} {"id": "PMID:1279883", "title": "Feline spongiform encephalopathy: fibril and PrP studies.", "content": "The brains from 18 cats were examined for the presence of the fibrils and modified PrP protein which are molecular diagnostic markers for scrapie-like diseases. Thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (FSE). Of these, five had histopathological changes of FSE, five had other lesions of the central nervous system, and in three the brain was normal. The remaining five cats had no clinical neurological signs and were selected as controls. Fibrils and modified PrP protein were found in the brains of the five cats with FSE and in one of the cats with neurological signs but no histopathological changes in the central nervous system. Fibrils were present in the absence of modified PrP in the brains of two cats, one with neurological signs and a histologically confirmed meningioma, and one with no neurological signs and a histologically normal brain.", "contents": "Feline spongiform encephalopathy: fibril and PrP studies. The brains from 18 cats were examined for the presence of the fibrils and modified PrP protein which are molecular diagnostic markers for scrapie-like diseases. Thirteen cats were referred with clinical neurological signs potentially indicative of feline spongiform encephalopathy (FSE). Of these, five had histopathological changes of FSE, five had other lesions of the central nervous system, and in three the brain was normal. The remaining five cats had no clinical neurological signs and were selected as controls. Fibrils and modified PrP protein were found in the brains of the five cats with FSE and in one of the cats with neurological signs but no histopathological changes in the central nervous system. Fibrils were present in the absence of modified PrP in the brains of two cats, one with neurological signs and a histologically confirmed meningioma, and one with no neurological signs and a histologically normal brain."} {"id": "PMID:1279884", "title": "Equine hyperlipaemia in the United Kingdom: clinical features and blood biochemistry of 18 cases.", "content": "The background, clinical signs, blood biochemistry and management of 18 cases of equine hyperlipaemia are described. Eleven of the animals were Shetland ponies, four were Welsh mountain ponies or their crosses, one was a fell pony and two were riding ponies of mixed breeding. Their average age was nine years. Fourteen of the cases were mares, of which nine were in foal and two were lactating; the remainder were geldings. Underlying or concurrent diseases were identified in only six animals, but in one other animal the hyperlipaemia appeared to have been precipitated by stress, and in another by undernutrition to prevent laminitis. Twelve of the animals were considered obese. There was no age, seasonal, or geographic bias to the distribution of cases. Plasma triglyceride concentrations were increased by between five- and 80-fold, and ranged from 4.7 to 78.8 mmol/litre. There was biochemical evidence of hepatic damage in 17 cases, of renal insufficiency in 15, and pancreatic pathology in three cases. Four animals were euthanased without therapy. The others were treated with oral glucose solutions, which were supplemented with injections of insulin and heparin in four cases, and insulin alone in two cases. Eight of the treated animals died, to give an overall mortality of 67 per cent. The outcome of the treatment was unrelated to the degree of hypertriglyceridaemia, to the presence and severity of hepatic, renal or pancreatic pathology or to the therapeutic regimen.", "contents": "Equine hyperlipaemia in the United Kingdom: clinical features and blood biochemistry of 18 cases. The background, clinical signs, blood biochemistry and management of 18 cases of equine hyperlipaemia are described. Eleven of the animals were Shetland ponies, four were Welsh mountain ponies or their crosses, one was a fell pony and two were riding ponies of mixed breeding. Their average age was nine years. Fourteen of the cases were mares, of which nine were in foal and two were lactating; the remainder were geldings. Underlying or concurrent diseases were identified in only six animals, but in one other animal the hyperlipaemia appeared to have been precipitated by stress, and in another by undernutrition to prevent laminitis. Twelve of the animals were considered obese. There was no age, seasonal, or geographic bias to the distribution of cases. Plasma triglyceride concentrations were increased by between five- and 80-fold, and ranged from 4.7 to 78.8 mmol/litre. There was biochemical evidence of hepatic damage in 17 cases, of renal insufficiency in 15, and pancreatic pathology in three cases. Four animals were euthanased without therapy. The others were treated with oral glucose solutions, which were supplemented with injections of insulin and heparin in four cases, and insulin alone in two cases. Eight of the treated animals died, to give an overall mortality of 67 per cent. The outcome of the treatment was unrelated to the degree of hypertriglyceridaemia, to the presence and severity of hepatic, renal or pancreatic pathology or to the therapeutic regimen."} {"id": "PMID:1279885", "title": "Early immunodiagnosis of bovine fascioliasis using the specific antigen f2 in a passive hemagglutination test.", "content": "An improved hemagglutination (HA) test using the purified specific f2 antigen of Fasciola hepatica has been evaluated with regard to its potential use for early diagnosis of infection. On experimental infection of beef calves 6-8 months of age, f2-specific antibodies were detected 2-4 weeks after inoculation and persisted at high levels during the 28 week experimental period. On natural infection of dairy calves, 6-9 months of age, allowed to graze in infected fields from April to June, 48% of the animals were positive in July although coproscopic analyses were negative. In November all the calves were HA positive but only 24% of them excreted F. hepatica eggs. Beef calves 1-3 months of age allowed to graze with their dams in infected fields continued to suckle their dams and were weakly infected according to HA results. This weak infection was not detected by coproscopical analysis. Colostral f2-specific antibodies persisted for approximately 6 months in the serum of dairy calves allowed to suckle their dams immediately after birth.", "contents": "Early immunodiagnosis of bovine fascioliasis using the specific antigen f2 in a passive hemagglutination test. An improved hemagglutination (HA) test using the purified specific f2 antigen of Fasciola hepatica has been evaluated with regard to its potential use for early diagnosis of infection. On experimental infection of beef calves 6-8 months of age, f2-specific antibodies were detected 2-4 weeks after inoculation and persisted at high levels during the 28 week experimental period. On natural infection of dairy calves, 6-9 months of age, allowed to graze in infected fields from April to June, 48% of the animals were positive in July although coproscopic analyses were negative. In November all the calves were HA positive but only 24% of them excreted F. hepatica eggs. Beef calves 1-3 months of age allowed to graze with their dams in infected fields continued to suckle their dams and were weakly infected according to HA results. This weak infection was not detected by coproscopical analysis. Colostral f2-specific antibodies persisted for approximately 6 months in the serum of dairy calves allowed to suckle their dams immediately after birth."} {"id": "PMID:1279886", "title": "Isolation and sequence of sheep immunoglobulin E heavy-chain complementary DNA.", "content": "A complementary DNA (cDNA) corresponding to sheep immunoglobulin E heavy (IgE H) chain messenger RNA (mRNA) was isolated and sequenced. A fragment of sheep IgE constant H (epsilon)-chain was initially synthesized using the polymerase chain reaction (PCR) and single-stranded cDNA prepared from the mRNA of parasite-stimulated sheep lymph nodes. This fragment was then used to probe a cDNA library, again prepared from a parasite-stimulated lymph node. A recombinant clone containing cDNA encoding a sheep IgE H-chain of 1802 base pairs was isolated and the H-chain cDNA-sequenced. The nucleotide sequence was found to code for a complete sheep IgE H-chain, consisting of both variable (V) and constant (C) regions. When the amino acid sequence derived from the nucleotide sequence was compared to other species epsilon-chains, interesting homologies and differences between corresponding domains were found, including conservation in cysteine and tryptophan residues and variable glycosylation sites.", "contents": "Isolation and sequence of sheep immunoglobulin E heavy-chain complementary DNA. A complementary DNA (cDNA) corresponding to sheep immunoglobulin E heavy (IgE H) chain messenger RNA (mRNA) was isolated and sequenced. A fragment of sheep IgE constant H (epsilon)-chain was initially synthesized using the polymerase chain reaction (PCR) and single-stranded cDNA prepared from the mRNA of parasite-stimulated sheep lymph nodes. This fragment was then used to probe a cDNA library, again prepared from a parasite-stimulated lymph node. A recombinant clone containing cDNA encoding a sheep IgE H-chain of 1802 base pairs was isolated and the H-chain cDNA-sequenced. The nucleotide sequence was found to code for a complete sheep IgE H-chain, consisting of both variable (V) and constant (C) regions. When the amino acid sequence derived from the nucleotide sequence was compared to other species epsilon-chains, interesting homologies and differences between corresponding domains were found, including conservation in cysteine and tryptophan residues and variable glycosylation sites."} {"id": "PMID:1279887", "title": "The role of insulin-like growth factors and IGF-binding proteins in the physiological and pathological processes of the kidney.", "content": "Insulin-like growth factors (IGFs) and their binding proteins are implicated in the growth regulation of the kidney during embryogenesis and differentiation. Recent evidence also suggests that IGFs play a role in kidney physiology (glomerular filtration rate, renal plasma flow) and pathology (diabetic renal hypertrophy, nephritis, glomerulosclerosis, kidney tumours, chronic renal failure). This review focuses on the biology of IGFs at the molecular, protein and receptor levels and considers their importance in renal physiology and pathology. The current data demonstrate a central role for the IGFs in the mediation of a wide variety of effects on renal growth, function and malignancy.", "contents": "The role of insulin-like growth factors and IGF-binding proteins in the physiological and pathological processes of the kidney. Insulin-like growth factors (IGFs) and their binding proteins are implicated in the growth regulation of the kidney during embryogenesis and differentiation. Recent evidence also suggests that IGFs play a role in kidney physiology (glomerular filtration rate, renal plasma flow) and pathology (diabetic renal hypertrophy, nephritis, glomerulosclerosis, kidney tumours, chronic renal failure). This review focuses on the biology of IGFs at the molecular, protein and receptor levels and considers their importance in renal physiology and pathology. The current data demonstrate a central role for the IGFs in the mediation of a wide variety of effects on renal growth, function and malignancy."} {"id": "PMID:1279888", "title": "Immunobiochemical characterization of the antigen detected by monoclonal antibody IND.64. Evidence that IND.64 reacts with the cell proliferation associated nuclear antigen previously defined by Ki-67.", "content": "The immunohistochemical characteristics of the monoclonal antibody IND.64 are very similar to those of the monoclonal antibody Ki-67. The aim of this study was to further characterize this new antibody and to compare it with Ki-67 using immunobiochemical methods. Our results demonstrate that the similarity between the antibodies holds true even at the molecular level. Immunoblot analysis of IM-9-cell lysates with both antibodies showed a double band with apparent molecular weights of 395 kD and 345 kD, respectively. Competition ELISAs using a synthetic peptide derived from the thus far determined Ki-67 cDNA sequence as competitor, indicate that IND.64 may recognize the same epitope as Ki-67. The IND.64 epitope resides at least within a 20 amino acid sequence which also contains the Ki-67 epitope. Since IND.64 is of the IgG2b subclass, while Ki-67 is of the IgG1 subclass, the two antibodies may be useful for double immunostaining. In addition, IND.64 may help in determining the still unknown function of the antigen it recognizes.", "contents": "Immunobiochemical characterization of the antigen detected by monoclonal antibody IND.64. Evidence that IND.64 reacts with the cell proliferation associated nuclear antigen previously defined by Ki-67. The immunohistochemical characteristics of the monoclonal antibody IND.64 are very similar to those of the monoclonal antibody Ki-67. The aim of this study was to further characterize this new antibody and to compare it with Ki-67 using immunobiochemical methods. Our results demonstrate that the similarity between the antibodies holds true even at the molecular level. Immunoblot analysis of IM-9-cell lysates with both antibodies showed a double band with apparent molecular weights of 395 kD and 345 kD, respectively. Competition ELISAs using a synthetic peptide derived from the thus far determined Ki-67 cDNA sequence as competitor, indicate that IND.64 may recognize the same epitope as Ki-67. The IND.64 epitope resides at least within a 20 amino acid sequence which also contains the Ki-67 epitope. Since IND.64 is of the IgG2b subclass, while Ki-67 is of the IgG1 subclass, the two antibodies may be useful for double immunostaining. In addition, IND.64 may help in determining the still unknown function of the antigen it recognizes."} {"id": "PMID:1279889", "title": "Atypical micromegakaryocytes, promegakaryoblasts and megakaryoblasts: a critical evaluation by immunohistochemistry, cytochemistry and morphometry of bone marrow trephines in chronic myeloid leukemia and myelodysplastic syndromes.", "content": "A morphometric analysis of bone marrow trephine biopsies has been performed to study the frequency and planimetric characteristics of so-called atypical micromegakaryocytes in chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS). In addition, an attempt was made to discriminate this particular cell population from small immature elements of megakaryocytopoiesis, such as promegakaryoblasts and megakaryoblasts. The staining reactions employed included periodic acid-Schiff (PAS), alpha-naphthyl acetate esterase (ANAE) and immunohistochemistry with a monoclonal antibody against platelet glycoprotein IIIa (Y2/51-CD61). Comparison of the various staining reactions applied to the different megakaryocytic elements together with morphometric measurements resulted in a clearcut identification of promegakaryoblasts. These were defined as the earliest immature and exclusively CD61-positive precursors. Atypical micromegakaryocytes were characterized by their dysplastic features and strong ANAE reactivity in addition to their positive CD61 staining. When stringent diagnostic criteria (diameter ranging between 10 to 15 microns, mean size about 12 microns) were applied, this abnormal cell population comprised less than 10% of total megakaryocytopoiesis in CML and MDS. It may be assumed that dysmegakaryocytic features in the latter disorders are partially generated by small to medium-sized megakaryocytes (diameter less than 30 microns). In conclusion, the relative frequency of promegakaryoblasts in the normal bone marrow (range 6-8%) is confirmed by evaluation of the immunohistochemical and cytochemical staining methods (CD61 and ANAE). Furthermore, the ANAE reaction facilitates the recognition of atypical micromegakaryocytes as well as small megakaryocytes. Thus cytochemistry provides a better insight into alterations of these cell lineages in various pathological conditions.", "contents": "Atypical micromegakaryocytes, promegakaryoblasts and megakaryoblasts: a critical evaluation by immunohistochemistry, cytochemistry and morphometry of bone marrow trephines in chronic myeloid leukemia and myelodysplastic syndromes. A morphometric analysis of bone marrow trephine biopsies has been performed to study the frequency and planimetric characteristics of so-called atypical micromegakaryocytes in chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS). In addition, an attempt was made to discriminate this particular cell population from small immature elements of megakaryocytopoiesis, such as promegakaryoblasts and megakaryoblasts. The staining reactions employed included periodic acid-Schiff (PAS), alpha-naphthyl acetate esterase (ANAE) and immunohistochemistry with a monoclonal antibody against platelet glycoprotein IIIa (Y2/51-CD61). Comparison of the various staining reactions applied to the different megakaryocytic elements together with morphometric measurements resulted in a clearcut identification of promegakaryoblasts. These were defined as the earliest immature and exclusively CD61-positive precursors. Atypical micromegakaryocytes were characterized by their dysplastic features and strong ANAE reactivity in addition to their positive CD61 staining. When stringent diagnostic criteria (diameter ranging between 10 to 15 microns, mean size about 12 microns) were applied, this abnormal cell population comprised less than 10% of total megakaryocytopoiesis in CML and MDS. It may be assumed that dysmegakaryocytic features in the latter disorders are partially generated by small to medium-sized megakaryocytes (diameter less than 30 microns). In conclusion, the relative frequency of promegakaryoblasts in the normal bone marrow (range 6-8%) is confirmed by evaluation of the immunohistochemical and cytochemical staining methods (CD61 and ANAE). Furthermore, the ANAE reaction facilitates the recognition of atypical micromegakaryocytes as well as small megakaryocytes. Thus cytochemistry provides a better insight into alterations of these cell lineages in various pathological conditions."} {"id": "PMID:1279890", "title": "Farber bodies found in murine phagocytes after injection of ceramides and related sphingolipids.", "content": "Mice were injected subcutaneously with a single dose of sphingolipids. The sphingolipids tested were: ceramide with alpha-hydroxy fatty acids, ceramide with non-hydroxy fatty acids, glucocerebroside, sphingomyelin, and galactocerebroside. Lipids without sphingolipids served as a control. The mice were sacrificed 1, 2, 3, 4, 5 and 7 days after injection. Three mice were used for each experiment. The subcutaneous tissue at the injected area, the liver and the spleen were studied histologically. At 1-3 days after injection, numerous cytoplasmic inclusion bodies were observed in the macrophages and fibroblasts in the subcutaneous tissue, but not in the liver or the spleen. Ultrastructural studies of the inclusion bodies indicated that the sphingolipids taken up by the phagocytes retained their respective original shape during the 1-3 day stage. At days 4 and 5, the number of the inclusion bodies decreased, but they contained Farber bodies, i.e. curvilinear bodies 12 to 25 nm wide and up to 120 nm long. The mice with galactocerebroside were an exception, with parallel leaflets structures, but without the Farber bodies.", "contents": "Farber bodies found in murine phagocytes after injection of ceramides and related sphingolipids. Mice were injected subcutaneously with a single dose of sphingolipids. The sphingolipids tested were: ceramide with alpha-hydroxy fatty acids, ceramide with non-hydroxy fatty acids, glucocerebroside, sphingomyelin, and galactocerebroside. Lipids without sphingolipids served as a control. The mice were sacrificed 1, 2, 3, 4, 5 and 7 days after injection. Three mice were used for each experiment. The subcutaneous tissue at the injected area, the liver and the spleen were studied histologically. At 1-3 days after injection, numerous cytoplasmic inclusion bodies were observed in the macrophages and fibroblasts in the subcutaneous tissue, but not in the liver or the spleen. Ultrastructural studies of the inclusion bodies indicated that the sphingolipids taken up by the phagocytes retained their respective original shape during the 1-3 day stage. At days 4 and 5, the number of the inclusion bodies decreased, but they contained Farber bodies, i.e. curvilinear bodies 12 to 25 nm wide and up to 120 nm long. The mice with galactocerebroside were an exception, with parallel leaflets structures, but without the Farber bodies."} {"id": "PMID:1279891", "title": "Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay.", "content": "The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells.", "contents": "Detection of multiple hormones and their mRNAs in human neuroblastoma cell line NB-1 using in situ hybridization, immunocytochemistry and radioimmunoassay. The production and secretion of multiple peptide hormones and tyrosine hydroxylase by the human neuroblastoma cell line NB-1 and the effects of dibutyryl cAMP (Bt2cAMP) and phorbol esters such as 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on them were investigated. The presence of messenger RNAs (mRNAs) of vasoactive intestinal peptide (VIP)/peptide histidine methionine (PHM), preprotachykinin, and tyrosine hydroxylase was detectable in the cytoplasm of cultured NB-1 cells by in situ hybridization. Treatment with Bt2cAMP and TPA markedly increased the number of cells immunoreactive to VIP, PHM, neuropeptide Y, Met-enkephalin, substance P and tyrosine hydroxylase and also the contents of VIP and Met-enkephalin in the culture medium. Bt2cAMP and TPA induced morphological changes characteristic of endocrine differentiation, such as an increase in neuroendocrine granules and the development of rough endoplasmic reticulum and Golgi apparatus. The results indicated that treatment with Bt2cAMP and TPA induces the expression of multiple genes of peptide hormone and tyrosine hydroxylase and increases hormone production and secretion through morphological changes into endocrine cells."} {"id": "PMID:1279892", "title": "Characteristics of small cell colonies developing in primary cultures of adult rat hepatocytes.", "content": "Phenotypes of the cells developing into small colonies after days of primary culture of adult rat hepatocytes in serum-free modified Dulbecco Modified Eagles' medium containing 10 mM nicotinamide and 10 ng/ml epidermal growth factor were analyzed immunocytochemically, cytochemically and ultrastructurally. Albumin, cytokeratin 8 and 18 were seen by immunocytochemical techniques in the cells of the small colonies at Day 6. Transferrin, alpha 1-antitrypsin, ceruloplasmin, and haptoglobin, proteins secreted by mature hepatocytes, were faintly stained in these cells as was alpha-fetoprotein. These proteins were secreted into the culture medium as evidenced by immunoblot analysis. gamma-Glutamyltransferase, alkaline phosphatase and glucose 6-phosphatase were not present in the cells of the small colonies as well as the surrounding hepatocytes at Day 6 of culture. In addition, ultrastructural examinations of the cells in the small colonies indicated that these cells not only had many characteristic mitochondria and desmosomes, but also a few small peroxisomes. Such cells, even after 20 days in culture were proliferating, as evidenced by the intranuclear presence of the proliferating cell nuclear antigen. The potential relation of these cells to hepatocytes which may serve as the principal reserve for replicating hepatocytes is discussed.", "contents": "Characteristics of small cell colonies developing in primary cultures of adult rat hepatocytes. Phenotypes of the cells developing into small colonies after days of primary culture of adult rat hepatocytes in serum-free modified Dulbecco Modified Eagles' medium containing 10 mM nicotinamide and 10 ng/ml epidermal growth factor were analyzed immunocytochemically, cytochemically and ultrastructurally. Albumin, cytokeratin 8 and 18 were seen by immunocytochemical techniques in the cells of the small colonies at Day 6. Transferrin, alpha 1-antitrypsin, ceruloplasmin, and haptoglobin, proteins secreted by mature hepatocytes, were faintly stained in these cells as was alpha-fetoprotein. These proteins were secreted into the culture medium as evidenced by immunoblot analysis. gamma-Glutamyltransferase, alkaline phosphatase and glucose 6-phosphatase were not present in the cells of the small colonies as well as the surrounding hepatocytes at Day 6 of culture. In addition, ultrastructural examinations of the cells in the small colonies indicated that these cells not only had many characteristic mitochondria and desmosomes, but also a few small peroxisomes. Such cells, even after 20 days in culture were proliferating, as evidenced by the intranuclear presence of the proliferating cell nuclear antigen. The potential relation of these cells to hepatocytes which may serve as the principal reserve for replicating hepatocytes is discussed."} {"id": "PMID:1279895", "title": "[Urinary amylase activity and debit as indices of the functional status of the pancreas and gallbladder].", "content": "The functional state was studied of the pancreas and gallbladder by calculation of the activity and yield of uroamylase in 96 persons. Data are compared that were obtained on the basis of this method. There was a clear correlation with results obtained during cholecystography. This simple and precise method may be recommended for wide practical use.", "contents": "[Urinary amylase activity and debit as indices of the functional status of the pancreas and gallbladder]. The functional state was studied of the pancreas and gallbladder by calculation of the activity and yield of uroamylase in 96 persons. Data are compared that were obtained on the basis of this method. There was a clear correlation with results obtained during cholecystography. This simple and precise method may be recommended for wide practical use."} {"id": "PMID:1279893", "title": "[Character of changes in protease inhibitory capacity of blood in experimental osteoarticular tuberculosis].", "content": "All the steps of osteoarticular tuberculosis evolution were accompanied by an increase in proteolytic activity in rabbit blood serum, which was compensated by activation of alpha 1-inhibitor of proteinases at the initial steps of osteitis. The system \"proteinases-inhibitors\" was imbalanced during the severe phases of arthritis independently on the rate of its development as follows: predominance of proteolytic potential over inhibitory activity, dissimilar activity of alpha 1-inhibitor of proteinases simultaneously with equal rate of alpha 2-macroglobulin content decrease. Dissimilar alterations in the system studied enabled to suggest that differential application of proteinases is suitable for treatment of inflammation with respect to the step of osteoarticular tuberculosis development.", "contents": "[Character of changes in protease inhibitory capacity of blood in experimental osteoarticular tuberculosis]. All the steps of osteoarticular tuberculosis evolution were accompanied by an increase in proteolytic activity in rabbit blood serum, which was compensated by activation of alpha 1-inhibitor of proteinases at the initial steps of osteitis. The system \"proteinases-inhibitors\" was imbalanced during the severe phases of arthritis independently on the rate of its development as follows: predominance of proteolytic potential over inhibitory activity, dissimilar activity of alpha 1-inhibitor of proteinases simultaneously with equal rate of alpha 2-macroglobulin content decrease. Dissimilar alterations in the system studied enabled to suggest that differential application of proteinases is suitable for treatment of inflammation with respect to the step of osteoarticular tuberculosis development."} {"id": "PMID:1279896", "title": "[Ebola virus reproduction in cell cultures].", "content": "Ebola-Zaire virus production in Vero and BGM cells was studied. The CPE developed in both cell cultures. The cell monolayer destruction by 80-90% was seen at a low multiplicity of infection in 7-8 days after virus inoculation. An overlay composition was developed for virus titration using plaque assay. The plaque production was shown to be directly proportional to the virus dose. The curve of Ebola virus production in Vero cell culture fluid was determined. At a multiplicity of infection of 0.01 PFU/cell, the maximum virus titer of 10(6.4) PFU/ml was reached in 7 days postinfection. Specific antisera were generated by inoculation of guinea pigs. Indirect immunofluorescent assay was used for testing of virus-specific antigen and antibody.", "contents": "[Ebola virus reproduction in cell cultures]. Ebola-Zaire virus production in Vero and BGM cells was studied. The CPE developed in both cell cultures. The cell monolayer destruction by 80-90% was seen at a low multiplicity of infection in 7-8 days after virus inoculation. An overlay composition was developed for virus titration using plaque assay. The plaque production was shown to be directly proportional to the virus dose. The curve of Ebola virus production in Vero cell culture fluid was determined. At a multiplicity of infection of 0.01 PFU/cell, the maximum virus titer of 10(6.4) PFU/ml was reached in 7 days postinfection. Specific antisera were generated by inoculation of guinea pigs. Indirect immunofluorescent assay was used for testing of virus-specific antigen and antibody."} {"id": "PMID:1279897", "title": "[The antigenic interrelationships between influenza A (H2) viruses determined by the mathematical processing of the data from immunoenzyme analysis using monoclonal antibodies to the M1 and NP proteins].", "content": "Antigenic relationships among 15 influenza A (H2) virus strains of human and avian origin were determined by ELISA titers with monoclonal antibodies (MCA) to Ml and NP proteins. Minor antigenic variations were found in Ml protein. One MCA to NP protein (469/6) showed different reactivity with human and avian influenza viruses. Analyses of antigenic relationships among influenza viruses were performed according to a computerized taxonomic cluster procedure. The evolutionary relatedness of these viruses is discussed.", "contents": "[The antigenic interrelationships between influenza A (H2) viruses determined by the mathematical processing of the data from immunoenzyme analysis using monoclonal antibodies to the M1 and NP proteins]. Antigenic relationships among 15 influenza A (H2) virus strains of human and avian origin were determined by ELISA titers with monoclonal antibodies (MCA) to Ml and NP proteins. Minor antigenic variations were found in Ml protein. One MCA to NP protein (469/6) showed different reactivity with human and avian influenza viruses. Analyses of antigenic relationships among influenza viruses were performed according to a computerized taxonomic cluster procedure. The evolutionary relatedness of these viruses is discussed."} {"id": "PMID:1279899", "title": "Molecular mimicry--hypothesis or reality?", "content": "A number of observations support molecular mimicry as a possible pathogenetic mechanism in diseases such as acute rheumatic fever, reactive arthritis after enteric infection or associated with Reiter's syndrome, myasthenia gravis, or even in rheumatoid arthritis. Molecular mimicry can be defined as a sharing of epitopes in linear or 3-dimensional presentation on disparate proteins from entirely different sources--for instance, group A streptococcal membranes and human cardiac myosin. How exposure to or infection with organisms sharing molecular similarity with antigens of the human host can evade tolerance and actually induce a self-reacting humoral or cellular immune response is still not clear; however, a large body of evidence has now been accumulated that documents apparent molecular mimicry mechanisms in these disorders. In some diseases, the molecular mimicry appears to involve human target organs and specific components of the infectious organism, whereas in others the host HLA cell surface molecules appear to share antigens with presumed bacterial or viral initiators of disease.", "contents": "Molecular mimicry--hypothesis or reality? A number of observations support molecular mimicry as a possible pathogenetic mechanism in diseases such as acute rheumatic fever, reactive arthritis after enteric infection or associated with Reiter's syndrome, myasthenia gravis, or even in rheumatoid arthritis. Molecular mimicry can be defined as a sharing of epitopes in linear or 3-dimensional presentation on disparate proteins from entirely different sources--for instance, group A streptococcal membranes and human cardiac myosin. How exposure to or infection with organisms sharing molecular similarity with antigens of the human host can evade tolerance and actually induce a self-reacting humoral or cellular immune response is still not clear; however, a large body of evidence has now been accumulated that documents apparent molecular mimicry mechanisms in these disorders. In some diseases, the molecular mimicry appears to involve human target organs and specific components of the infectious organism, whereas in others the host HLA cell surface molecules appear to share antigens with presumed bacterial or viral initiators of disease."} {"id": "PMID:1279900", "title": "[Evolution of morphological and clinical changes in mesangial proliferative glomerulonephritis].", "content": "The clinical and morphological analysis is reported of the changes evolving in 12 cases of mesangial proliferative glomerulonephritis based on repeated biopsies carried out at intervals from 1 to 7 years. Clinical findings at the time of the first biopsy included in 2 cases nephrotic syndrome, and in the remaining cases proteinuria ranging from 0.3 to 2/1000. In all cases erythrocytes in urine were present ranging from 4-6 to 50-100 erythrocytes per field of vision. Hypertension was found in 4 cases, and increased serum creatinine level in 1 patient. At the time of repeated biopsy in 11 cases clinical evidence of improvement was noted with decreased proteinuria anderythrocytes in urine. In 1 case worsening was found and several months later signs of renal failure developed which led to death. The morphological examinations demonstrated in the first biopsies mesangial proliferative glomerulonephritis. In second biopsies these findings were confirmed. In 1 case with unfavourable outcome the changes became more pronounced, and in the remaining ones no significant differences were noted in relation to the first biopsy which evidenced lack of a close correlation between the clinical condition and the morphological state of the kidneys.", "contents": "[Evolution of morphological and clinical changes in mesangial proliferative glomerulonephritis]. The clinical and morphological analysis is reported of the changes evolving in 12 cases of mesangial proliferative glomerulonephritis based on repeated biopsies carried out at intervals from 1 to 7 years. Clinical findings at the time of the first biopsy included in 2 cases nephrotic syndrome, and in the remaining cases proteinuria ranging from 0.3 to 2/1000. In all cases erythrocytes in urine were present ranging from 4-6 to 50-100 erythrocytes per field of vision. Hypertension was found in 4 cases, and increased serum creatinine level in 1 patient. At the time of repeated biopsy in 11 cases clinical evidence of improvement was noted with decreased proteinuria anderythrocytes in urine. In 1 case worsening was found and several months later signs of renal failure developed which led to death. The morphological examinations demonstrated in the first biopsies mesangial proliferative glomerulonephritis. In second biopsies these findings were confirmed. In 1 case with unfavourable outcome the changes became more pronounced, and in the remaining ones no significant differences were noted in relation to the first biopsy which evidenced lack of a close correlation between the clinical condition and the morphological state of the kidneys."} {"id": "PMID:1279898", "title": "[Inhibition of the reproduction of the influenza B virus by aprotinin].", "content": "Injection of aprotinin, a natural inhibitor of proteinases, into the allantoic cavity of chick embryos infected with influenza B/Lee/40 or B/HK/73 virus resulted in inhibition of proteolytic cleavage of virus hemagglutinin HA into HA1 and HA2, thereby decreasing the level of proteolytic activation of the synthesized virus particles. As a result of this inhibition in aprotinin-treated embryos, multicycle virus reproduction was limited and virus yields decreased considerably. The experimental results indicate the potential of chemotherapeutic inhibition of infection caused by influenza B viruses using antiproteinase agents interfering with proteolytic activation of virions.", "contents": "[Inhibition of the reproduction of the influenza B virus by aprotinin]. Injection of aprotinin, a natural inhibitor of proteinases, into the allantoic cavity of chick embryos infected with influenza B/Lee/40 or B/HK/73 virus resulted in inhibition of proteolytic cleavage of virus hemagglutinin HA into HA1 and HA2, thereby decreasing the level of proteolytic activation of the synthesized virus particles. As a result of this inhibition in aprotinin-treated embryos, multicycle virus reproduction was limited and virus yields decreased considerably. The experimental results indicate the potential of chemotherapeutic inhibition of infection caused by influenza B viruses using antiproteinase agents interfering with proteolytic activation of virions."} {"id": "PMID:1279902", "title": "[Modern procedures in detecting viral antigens].", "content": "Besides serology and virus isolation, assays for the detection of viral antigens or nucleic acids are of increasing importance in routine diagnosis of viral infectious diseases. Critical steps, however, are the selection of suitable assays and specimens. With respect to clinical diagnosis, novel ultrasensitive methods for in vitro DNA amplification like polymerase chain reaction or ligase chain reaction are of high diagnostic significance e.g. for the demonstration of herpes simplex virus DNA in CSF samples or hepatitis C virus in patient sera.", "contents": "[Modern procedures in detecting viral antigens]. Besides serology and virus isolation, assays for the detection of viral antigens or nucleic acids are of increasing importance in routine diagnosis of viral infectious diseases. Critical steps, however, are the selection of suitable assays and specimens. With respect to clinical diagnosis, novel ultrasensitive methods for in vitro DNA amplification like polymerase chain reaction or ligase chain reaction are of high diagnostic significance e.g. for the demonstration of herpes simplex virus DNA in CSF samples or hepatitis C virus in patient sera."} {"id": "PMID:1279903", "title": "[Poor reproducibility of parameters of heart rate variations].", "content": "The analysis of heart rate variability is supposed to be a marker of autonomic cardiac activity and is used for risk stratification of post-infarction patients. Analysis of heart rate variability in the frequency domain may permit a differentiation of vagal and sympathetic control; for such analyses only short time intervals characterized by a steady-state autonomic balance can be used. Yet, it is unclear whether single determinations of heart rate variability indices derived from short time intervals yield reproducible results. Therefore, the reproducibility of heart rate variability indices was studied with weekly measurements in 10 healthy volunteers under the following defined conditions: 13 min supine rest, 10 min standing, 13 min sitting, and 15 min cycle ergometry followed by a 14 min recovery period. Heart rate variability was determined in the frequency domain (fast Fourier transformation) and in the time domain. The reproducibility was estimated by the coefficient of variation (CV). Additionally, the reproducibility of heart rate, blood pressure, and the expiratory-inspiratory ratio of heart rate was determined. The reproducibility of the frequency domain indices (36.6-74.9% CV) and of the time domain indices (19.6-32.8% CV) was considerably worse than that of heart rate (5.2-8.2% CV), blood pressure (5.1-8.2% CV) and the expiratory-inspiratory ratio of heart rate (4.6% CV). The reproducibility of heart rate variability indices was not improved by orthostatic or ergometric challenge. This poor reproducibility does not permit a reliable interpretation of heart rate variability on the basis of single measurements in healthy volunteers. Given the wide range and scatter of the measured parameters, the diagnostic and prognostic value of heart rate variability indices derived from short recording periods appears questionable.", "contents": "[Poor reproducibility of parameters of heart rate variations]. The analysis of heart rate variability is supposed to be a marker of autonomic cardiac activity and is used for risk stratification of post-infarction patients. Analysis of heart rate variability in the frequency domain may permit a differentiation of vagal and sympathetic control; for such analyses only short time intervals characterized by a steady-state autonomic balance can be used. Yet, it is unclear whether single determinations of heart rate variability indices derived from short time intervals yield reproducible results. Therefore, the reproducibility of heart rate variability indices was studied with weekly measurements in 10 healthy volunteers under the following defined conditions: 13 min supine rest, 10 min standing, 13 min sitting, and 15 min cycle ergometry followed by a 14 min recovery period. Heart rate variability was determined in the frequency domain (fast Fourier transformation) and in the time domain. The reproducibility was estimated by the coefficient of variation (CV). Additionally, the reproducibility of heart rate, blood pressure, and the expiratory-inspiratory ratio of heart rate was determined. The reproducibility of the frequency domain indices (36.6-74.9% CV) and of the time domain indices (19.6-32.8% CV) was considerably worse than that of heart rate (5.2-8.2% CV), blood pressure (5.1-8.2% CV) and the expiratory-inspiratory ratio of heart rate (4.6% CV). The reproducibility of heart rate variability indices was not improved by orthostatic or ergometric challenge. This poor reproducibility does not permit a reliable interpretation of heart rate variability on the basis of single measurements in healthy volunteers. Given the wide range and scatter of the measured parameters, the diagnostic and prognostic value of heart rate variability indices derived from short recording periods appears questionable."} {"id": "PMID:1279905", "title": "Comparison of capsid protein VP1 of the viruses used for the production and challenge of foot-and-mouth disease vaccines in Spain.", "content": "A significant frequency of amino acid substitutions, that affect important antigenic sites on capsid protein VP1, has been found among viral preparations used for the production and for challenge, in protection assays, of foot-and-mouth disease (FMD) vaccines. The amino acid substitutions present in one of the viruses studied abolished its reactivity with two neutralizing monoclonal antibodies that recognized different epitopes on VP1. Thus, the results obtained illustrate the high potential for antigenic variation introduced by the multiple cycles of growth usually undergone by the strains used for the production and challenge of FMD vaccines.", "contents": "Comparison of capsid protein VP1 of the viruses used for the production and challenge of foot-and-mouth disease vaccines in Spain. A significant frequency of amino acid substitutions, that affect important antigenic sites on capsid protein VP1, has been found among viral preparations used for the production and for challenge, in protection assays, of foot-and-mouth disease (FMD) vaccines. The amino acid substitutions present in one of the viruses studied abolished its reactivity with two neutralizing monoclonal antibodies that recognized different epitopes on VP1. Thus, the results obtained illustrate the high potential for antigenic variation introduced by the multiple cycles of growth usually undergone by the strains used for the production and challenge of FMD vaccines."} {"id": "PMID:1279906", "title": "Construction of synthetic immunogens: use of T- and B-cell epitopes of CS and RESA proteins of Plasmodium falciparum.", "content": "An invariant T-helper epitope of the sequence ENDIEKKICKMEKCSSVFNV (residue no. 376-395) from the circumsporozoite (CS) protein was coupled chemically with the repeat sequences, namely (EENV)2, EENVEHDA and DDEHVEEPTVA, of ring-infected erythrocyte surface antigen (RESA) protein of Plasmodium falciparum. The CS sequence was tested for helper and proliferative activity in five inbred strains of mice of different haplotypes. The CS peptide showed dose-dependent lymphocyte proliferative response in all the strains tested. On the other hand, no proliferative response was observed with the dimers of the three RESA repeat sequences. The antibody levels in these strains immunized with RESA-CS hybrid structures showed high titres and a booster effect during subsequent immunization. Such a phenomenon was not observed with RESA peptides alone. The above CS sequence could be an ideal T-helper epitope which can be linked to hydrophilic B-cell epitopes of the RESA sequence to overcome major histocompatibility complex restriction in the host.", "contents": "Construction of synthetic immunogens: use of T- and B-cell epitopes of CS and RESA proteins of Plasmodium falciparum. An invariant T-helper epitope of the sequence ENDIEKKICKMEKCSSVFNV (residue no. 376-395) from the circumsporozoite (CS) protein was coupled chemically with the repeat sequences, namely (EENV)2, EENVEHDA and DDEHVEEPTVA, of ring-infected erythrocyte surface antigen (RESA) protein of Plasmodium falciparum. The CS sequence was tested for helper and proliferative activity in five inbred strains of mice of different haplotypes. The CS peptide showed dose-dependent lymphocyte proliferative response in all the strains tested. On the other hand, no proliferative response was observed with the dimers of the three RESA repeat sequences. The antibody levels in these strains immunized with RESA-CS hybrid structures showed high titres and a booster effect during subsequent immunization. Such a phenomenon was not observed with RESA peptides alone. The above CS sequence could be an ideal T-helper epitope which can be linked to hydrophilic B-cell epitopes of the RESA sequence to overcome major histocompatibility complex restriction in the host."} {"id": "PMID:1279904", "title": "[Palliative minimally invasive therapy in inoperable elderly patients].", "content": "The results of palliative endoscopic therapeutic maneuvers in patients over 80 years of age were retrospectively analyzed, covering a time period of 26 months. Aims of the therapeutic modalities were the recanalization of stenoses of the gastrointestinal tract, the long-term enteral nutrition or the abolition of a malignant obstructive jaundice. Appropriate procedures were combined bougienage and laser therapy, implantation of esophageal bridging tubes, percutaneous endoscopic gastroenterostomy (PEG), and the implantation of biliary endoprosthesis after endoscopic papillotomy. We evaluated (during the period January 1, 1990 until February 29, 1992) a total of 89 patients with various diseases, all of whom, at the time of examination, were candidates for surgery, either due to the extent of a tumor or due to a significant reduction of the physical status. The complication rate of the procedures of 2.9%, and the lethality risk of 0.9% showed no increase compared to patients of younger age. Therefore, minimal invasive endoscopic therapeutic procedures are strongly indicated in inoperable patients suffering from various diseases. Symptoms may be eliminated or significantly reduced with a few procedures which can be repeated many times.", "contents": "[Palliative minimally invasive therapy in inoperable elderly patients]. The results of palliative endoscopic therapeutic maneuvers in patients over 80 years of age were retrospectively analyzed, covering a time period of 26 months. Aims of the therapeutic modalities were the recanalization of stenoses of the gastrointestinal tract, the long-term enteral nutrition or the abolition of a malignant obstructive jaundice. Appropriate procedures were combined bougienage and laser therapy, implantation of esophageal bridging tubes, percutaneous endoscopic gastroenterostomy (PEG), and the implantation of biliary endoprosthesis after endoscopic papillotomy. We evaluated (during the period January 1, 1990 until February 29, 1992) a total of 89 patients with various diseases, all of whom, at the time of examination, were candidates for surgery, either due to the extent of a tumor or due to a significant reduction of the physical status. The complication rate of the procedures of 2.9%, and the lethality risk of 0.9% showed no increase compared to patients of younger age. Therefore, minimal invasive endoscopic therapeutic procedures are strongly indicated in inoperable patients suffering from various diseases. Symptoms may be eliminated or significantly reduced with a few procedures which can be repeated many times."} {"id": "PMID:1279908", "title": "Saccharomyces cerevisiae contains a homolog of human FKBP-13, a membrane-associated FK506/rapamycin binding protein.", "content": "FKB2 encodes a homolog of human FKBP-13, a membrane-associated binding protein for the immunosuppressants FK506 and rapamycin. FKB2 is located on the right arm of chromosome IV and contains an open reading frame of 135 amino acids, of which the first 17 residues comprise a putative hydrophobic leader peptide. Yeast FKBP-13 is homologous to human FKBP-13 (52% amino acid identity) and to FKBP-12, the major cytosolic receptor for FK506. In the alignment of FKBP-13 and FKBP-12 sequences, there are 28 invariant residues. Among these conserved residues are those that comprise the drug binding and peptidyl-prolyl cis-trans isomerase active site of FKBP-12. The phylogenetic conservation of the FKBP family suggest that the proteins are involved in a basic cellular function.", "contents": "Saccharomyces cerevisiae contains a homolog of human FKBP-13, a membrane-associated FK506/rapamycin binding protein. FKB2 encodes a homolog of human FKBP-13, a membrane-associated binding protein for the immunosuppressants FK506 and rapamycin. FKB2 is located on the right arm of chromosome IV and contains an open reading frame of 135 amino acids, of which the first 17 residues comprise a putative hydrophobic leader peptide. Yeast FKBP-13 is homologous to human FKBP-13 (52% amino acid identity) and to FKBP-12, the major cytosolic receptor for FK506. In the alignment of FKBP-13 and FKBP-12 sequences, there are 28 invariant residues. Among these conserved residues are those that comprise the drug binding and peptidyl-prolyl cis-trans isomerase active site of FKBP-12. The phylogenetic conservation of the FKBP family suggest that the proteins are involved in a basic cellular function."} {"id": "PMID:1279909", "title": "Antibodies directed against a yeast carboxyl-terminal peroxisomal targeting signal specifically recognize peroxisomal proteins from various yeasts.", "content": "The carboxyl-terminal tripeptide Ala-Lys-Ile is essential for targeting Candida tropicalis trifunctional enzyme (hydratase-dehydrogenase-epimerase) to peroxisomes of both Candida albicans and Saccharomyces cerevisiae (Aitchison,J.D., Murray, W.W. and Rachubinski, R. A. (1991).J. Biol. Chem. 266, 23197-23203). We investigated the possibility that this tripeptide may act as a general peroxisomal targeting signal (PTS) for other proteins in the yeasts C. tropicalis, C. albicans, Yarrowia lipolytica and S. cerevisiae, and in rat liver. Anti-AKI antibodies raised against the carboxyl-terminal 12 amino acids of trifunctional enzyme were used to search for this PTS in proteins of these yeasts and of rat liver. The anti-AKI antibodies reacted exclusively with multiple peroxisomal proteins from the yeasts C. tropicalis, C. albicans and Y. lipolytica. There was a weak reaction of the antibodies with one peroxisomal protein from S. cerevisiae and no reaction with peroxisomal proteins from rat liver. Antibodies directed against a synthetic peptide containing a carboxyl-terminal Ser-Lys-Leu PTS (Gould, S. J., Krisans, S., Keller, G.-A. and Subramani, S. (1990). J. Cell Biol. 110,27-34) reacted with multiple peroxisomal proteins of rat liver and with peroxisomal proteins of yeast distinct from those identified with anti-AKI antibodies. These results provide evidence that several peroxisomal proteins of different yeasts contain a PTS antigenically similar to that of C. tropicalis trifunctional enzyme and that this signal is absent from peroxisomal proteins from at least one mammalian system, rat liver.", "contents": "Antibodies directed against a yeast carboxyl-terminal peroxisomal targeting signal specifically recognize peroxisomal proteins from various yeasts. The carboxyl-terminal tripeptide Ala-Lys-Ile is essential for targeting Candida tropicalis trifunctional enzyme (hydratase-dehydrogenase-epimerase) to peroxisomes of both Candida albicans and Saccharomyces cerevisiae (Aitchison,J.D., Murray, W.W. and Rachubinski, R. A. (1991).J. Biol. Chem. 266, 23197-23203). We investigated the possibility that this tripeptide may act as a general peroxisomal targeting signal (PTS) for other proteins in the yeasts C. tropicalis, C. albicans, Yarrowia lipolytica and S. cerevisiae, and in rat liver. Anti-AKI antibodies raised against the carboxyl-terminal 12 amino acids of trifunctional enzyme were used to search for this PTS in proteins of these yeasts and of rat liver. The anti-AKI antibodies reacted exclusively with multiple peroxisomal proteins from the yeasts C. tropicalis, C. albicans and Y. lipolytica. There was a weak reaction of the antibodies with one peroxisomal protein from S. cerevisiae and no reaction with peroxisomal proteins from rat liver. Antibodies directed against a synthetic peptide containing a carboxyl-terminal Ser-Lys-Leu PTS (Gould, S. J., Krisans, S., Keller, G.-A. and Subramani, S. (1990). J. Cell Biol. 110,27-34) reacted with multiple peroxisomal proteins of rat liver and with peroxisomal proteins of yeast distinct from those identified with anti-AKI antibodies. These results provide evidence that several peroxisomal proteins of different yeasts contain a PTS antigenically similar to that of C. tropicalis trifunctional enzyme and that this signal is absent from peroxisomal proteins from at least one mammalian system, rat liver."} {"id": "PMID:1279907", "title": "[The participation of RNA synthesis in the process of the acquisition and retention of conditioned reflexes (a study using antifeins)].", "content": "RNA-synthesizing activity of neuronal nuclei in the neocortex of rats increases after the termination of conditioning depending on the degree of learning. RNA synthesis shifts induced by propylnorantifein and the demethylated derivatives of ethylnorantifein are correlated only with the influence of the drugs on the retention but not the learning. Participation of RNA synthesis by the neurons of the neocortex in the mechanisms of long-term memory is discussed.", "contents": "[The participation of RNA synthesis in the process of the acquisition and retention of conditioned reflexes (a study using antifeins)]. RNA-synthesizing activity of neuronal nuclei in the neocortex of rats increases after the termination of conditioning depending on the degree of learning. RNA synthesis shifts induced by propylnorantifein and the demethylated derivatives of ethylnorantifein are correlated only with the influence of the drugs on the retention but not the learning. Participation of RNA synthesis by the neurons of the neocortex in the mechanisms of long-term memory is discussed."} {"id": "PMID:1279910", "title": "[Effect of long-term feeding with tryptophan-free diet on the circadian rhythm in rats].", "content": "Effects of long-term feeding with tryptophan (TRP)-free diet on the free running periods of wheel-running rhythm and the central serotonergic neurotransmission were examined in male blinded rats. Long-term feeding with TRP-free diet did not change the periods of wheel-running rhythm calculated from chi 2 periodogram but disordered its pattern, which seemed to be due to masking or entrainment effects. On the other hand, long-term TRP-free diet decreased the concentrations of TRP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in all brain regions tested; frontal cortex, hippocampus, thalamus, hypothalamus and pons. The density of 5-HT1A receptor (3H-8-OH-DPAT) binding was significantly decreased in only frontal cortex, while no significant change was observed in the density of 5-HT2 receptor (3H-ketanserin) binding in all regions. Although the mechanism of down-regulation of 5-HT1A receptor in frontal cortex is obscure, it was confirmed that TRP-free diet decreased central 5-HT synthesis and 5-HT neurotransmission. This dysfunction of 5-HT neurotransmission by TRP-free diet is suggested to make the circadian rhythm pacemaker susceptible to subtle environmental factors by lowering its intensity.", "contents": "[Effect of long-term feeding with tryptophan-free diet on the circadian rhythm in rats]. Effects of long-term feeding with tryptophan (TRP)-free diet on the free running periods of wheel-running rhythm and the central serotonergic neurotransmission were examined in male blinded rats. Long-term feeding with TRP-free diet did not change the periods of wheel-running rhythm calculated from chi 2 periodogram but disordered its pattern, which seemed to be due to masking or entrainment effects. On the other hand, long-term TRP-free diet decreased the concentrations of TRP, 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in all brain regions tested; frontal cortex, hippocampus, thalamus, hypothalamus and pons. The density of 5-HT1A receptor (3H-8-OH-DPAT) binding was significantly decreased in only frontal cortex, while no significant change was observed in the density of 5-HT2 receptor (3H-ketanserin) binding in all regions. Although the mechanism of down-regulation of 5-HT1A receptor in frontal cortex is obscure, it was confirmed that TRP-free diet decreased central 5-HT synthesis and 5-HT neurotransmission. This dysfunction of 5-HT neurotransmission by TRP-free diet is suggested to make the circadian rhythm pacemaker susceptible to subtle environmental factors by lowering its intensity."} {"id": "PMID:1279911", "title": "[Psychogenesis of the course of Sudeck's disease--a case report].", "content": "Several authors have already pointed out the significance of personality, subjectively stressful life events and relevant conflicts for the course of reflex sympathetic dystrophy. Psychodynamic hypotheses are demonstrated by two patients who had psychotherapeutic treatment and were observed over a longer stretch of time. A therapeutic concept which is enriched by this knowledge may obtain the patients' better compliance with orthopaedists, surgeons and physiotherapists and may influence duration of illness and treatment results favorably.", "contents": "[Psychogenesis of the course of Sudeck's disease--a case report]. Several authors have already pointed out the significance of personality, subjectively stressful life events and relevant conflicts for the course of reflex sympathetic dystrophy. Psychodynamic hypotheses are demonstrated by two patients who had psychotherapeutic treatment and were observed over a longer stretch of time. A therapeutic concept which is enriched by this knowledge may obtain the patients' better compliance with orthopaedists, surgeons and physiotherapists and may influence duration of illness and treatment results favorably."} {"id": "PMID:1279912", "title": "[The effect of Shigella sonnei strains opposite in their virulence on different links in the immune system].", "content": "For the first time different action of S. sonnei strains, opposite in their virulence, on hematopoiesis and the functional activity of T- and B-lymphocytes has been shown. The hematopoiesis-disturbing action of virulent shigellae is manifested by their capacity, more pronounced than similar capacity of an avirulent (vaccine) strain, for stimulating the processes of endo- and exocolony formation, the proliferation of hematopoietic stem cells and their migration to the blood. The effect produced by shigellae on T-cell-mediated immune response is manifested by the suppression of macrophage migration and its subsequent activation, whose manifestations and duration depend on the virulence of S. sonnei strains under study. The modulating effect of S. sonnei on B-cell-mediated immune reactions is manifested by the inhibiting action of S. sonnei virulent strain and the stimulating action of S. sonnei vaccine strain on the formation of antibody-producing cells synthesizing S. sonnei lipopolysaccharide antibodies shortly after the injection of shigellae. The results of this study indicate that S. sonnei virulent and avirulent (vaccine) produce multifunctional and differing effects on cell-mediated immune reactions, these processes being dependent on the virulence of shigellae and their individual specific antigens.", "contents": "[The effect of Shigella sonnei strains opposite in their virulence on different links in the immune system]. For the first time different action of S. sonnei strains, opposite in their virulence, on hematopoiesis and the functional activity of T- and B-lymphocytes has been shown. The hematopoiesis-disturbing action of virulent shigellae is manifested by their capacity, more pronounced than similar capacity of an avirulent (vaccine) strain, for stimulating the processes of endo- and exocolony formation, the proliferation of hematopoietic stem cells and their migration to the blood. The effect produced by shigellae on T-cell-mediated immune response is manifested by the suppression of macrophage migration and its subsequent activation, whose manifestations and duration depend on the virulence of S. sonnei strains under study. The modulating effect of S. sonnei on B-cell-mediated immune reactions is manifested by the inhibiting action of S. sonnei virulent strain and the stimulating action of S. sonnei vaccine strain on the formation of antibody-producing cells synthesizing S. sonnei lipopolysaccharide antibodies shortly after the injection of shigellae. The results of this study indicate that S. sonnei virulent and avirulent (vaccine) produce multifunctional and differing effects on cell-mediated immune reactions, these processes being dependent on the virulence of shigellae and their individual specific antigens."} {"id": "PMID:1279913", "title": "[Antibody avidity in candidiasis patients].", "content": "The properties of antibodies to Candida albicans in healthy persons, candidiasis patients and patients with somatic pathology of nonmycotic genesis were studied. Healthy persons were found to have the highest avidity of antibodies at the minimal neutralizing dose of the antigen. In all groups the titers of antibodies were inversely related to their avidity.", "contents": "[Antibody avidity in candidiasis patients]. The properties of antibodies to Candida albicans in healthy persons, candidiasis patients and patients with somatic pathology of nonmycotic genesis were studied. Healthy persons were found to have the highest avidity of antibodies at the minimal neutralizing dose of the antigen. In all groups the titers of antibodies were inversely related to their avidity."} {"id": "PMID:1279915", "title": "Surgical treatment of post-traumatic defects of the soft tissues of the head with necrosis of the calvarial bones.", "content": "Experience with the treatment of patients with defects of the soft tissues of the head and necrosis of the calvarial bones has been generalized. Results of treatment using multiple craniotomy, osteonecrectomy and various methods of dermatoplasty aiming at restoration of the skin cover are discussed. The methods of treatment focused on the preservation of osteonecrotic parts and thus the hard integument of the calvaria ensuring prevention of intracranial suppurative complications, creation of a full-value skin cover, a more favourable outcome of injury and work ability of the patients are discussed and recommended.", "contents": "Surgical treatment of post-traumatic defects of the soft tissues of the head with necrosis of the calvarial bones. Experience with the treatment of patients with defects of the soft tissues of the head and necrosis of the calvarial bones has been generalized. Results of treatment using multiple craniotomy, osteonecrectomy and various methods of dermatoplasty aiming at restoration of the skin cover are discussed. The methods of treatment focused on the preservation of osteonecrotic parts and thus the hard integument of the calvaria ensuring prevention of intracranial suppurative complications, creation of a full-value skin cover, a more favourable outcome of injury and work ability of the patients are discussed and recommended."} {"id": "PMID:1279916", "title": "Rationale for the need to employ a conservative method in the treatment of patients with dystrophy of the hand.", "content": "Radioimmunoassay determining sexual hormone levels, functional state of the autonomic nervous system and blood supply, were used to study the causes aiding the development of dystrophies of the hand in women. All these conditions were found to be associated with gross disorders of the endocrine system, autonomic dysfunction and changes in the system of blood supply. The results were used to develop a policy for the selection of the therapeutic method and its timing with a favourable effect.", "contents": "Rationale for the need to employ a conservative method in the treatment of patients with dystrophy of the hand. Radioimmunoassay determining sexual hormone levels, functional state of the autonomic nervous system and blood supply, were used to study the causes aiding the development of dystrophies of the hand in women. All these conditions were found to be associated with gross disorders of the endocrine system, autonomic dysfunction and changes in the system of blood supply. The results were used to develop a policy for the selection of the therapeutic method and its timing with a favourable effect."} {"id": "PMID:1279920", "title": "Age-dependent changes in the size of the upper lip in Bulgarians.", "content": "Age-dependent changes in the width and height of the upper lip were studied in 2,300 healthy Bulgarians aged from 3 days to 102 years, for the purposes of cheiloplasty in surgery and of visual art. It has been established that at the moment of birth, the upper lip is one of the most developed organs of the human body in both sexes and that it grows in size up to the age of 80 years, completing its intensive growth during the pre-school age while in the years of puberty it does not show the growth jump characteristic of the organism as a whole. In the males, the lip remains larger during the whole period of postnatal ontogenesis except for the early childhood; the difference in the height is most expressed (3.08 mm) in the 9th decade, and in the width (5.24 mm) even later. The conclusion has been drawn that cheiloplasty can be performed at any age including the first days after birth, the dimensions obtained at the age intervals under study serving as standards.", "contents": "Age-dependent changes in the size of the upper lip in Bulgarians. Age-dependent changes in the width and height of the upper lip were studied in 2,300 healthy Bulgarians aged from 3 days to 102 years, for the purposes of cheiloplasty in surgery and of visual art. It has been established that at the moment of birth, the upper lip is one of the most developed organs of the human body in both sexes and that it grows in size up to the age of 80 years, completing its intensive growth during the pre-school age while in the years of puberty it does not show the growth jump characteristic of the organism as a whole. In the males, the lip remains larger during the whole period of postnatal ontogenesis except for the early childhood; the difference in the height is most expressed (3.08 mm) in the 9th decade, and in the width (5.24 mm) even later. The conclusion has been drawn that cheiloplasty can be performed at any age including the first days after birth, the dimensions obtained at the age intervals under study serving as standards."} {"id": "PMID:1279921", "title": "Repair of anterior secondary palate fistula using tongue flaps.", "content": "Seventy-two cases of palatal fistulae are presented. The location on anterior part of secondary palate is due to lack of double layer closure. Vascular pattern of tongue is detailed. Operative details of using tongue flap as oral layer in closure of fistula are described. Undue mobility of tongue and prevention of breakdown of tongue flap repair incidence of which is low in present series are mentioned. It is suggested as excellent method of closure of palatal fistulae in difficult cases.", "contents": "Repair of anterior secondary palate fistula using tongue flaps. Seventy-two cases of palatal fistulae are presented. The location on anterior part of secondary palate is due to lack of double layer closure. Vascular pattern of tongue is detailed. Operative details of using tongue flap as oral layer in closure of fistula are described. Undue mobility of tongue and prevention of breakdown of tongue flap repair incidence of which is low in present series are mentioned. It is suggested as excellent method of closure of palatal fistulae in difficult cases."} {"id": "PMID:1279922", "title": "Treatment of donor sites--calcium alginate versus paraffin gauze.", "content": "In the surgery of burns a good healing of donor areas is essential. A controlled trial of 17 cases is presented. Mirror-image donor areas in the same patient were treated on one leg with a traditional dressing of paraffin gauze, Jelonet, on the other leg with Kaltostat, a calcium sodium alginate wound dressing. Healing time, haemostasis, ease and comfort with removal, dressings, infection and quality of the regenerated skin, were estimated. The Kaltostat dressing seemed to be superior due to the quality of the re-epithelialized donor site, the haemostatic quality and the ease and comfort with removal. There was a marginal profit in healing time.", "contents": "Treatment of donor sites--calcium alginate versus paraffin gauze. In the surgery of burns a good healing of donor areas is essential. A controlled trial of 17 cases is presented. Mirror-image donor areas in the same patient were treated on one leg with a traditional dressing of paraffin gauze, Jelonet, on the other leg with Kaltostat, a calcium sodium alginate wound dressing. Healing time, haemostasis, ease and comfort with removal, dressings, infection and quality of the regenerated skin, were estimated. The Kaltostat dressing seemed to be superior due to the quality of the re-epithelialized donor site, the haemostatic quality and the ease and comfort with removal. There was a marginal profit in healing time."} {"id": "PMID:1279923", "title": "Micrognathia in myasthenia gravis case report.", "content": "Micrognathia is a disease which can appear in patients with myasthenia gravis. If patients with MG are adequately neurologically prepared they may undergo aesthetic, functional operation, which leads to improvement in the course of the disease.", "contents": "Micrognathia in myasthenia gravis case report. Micrognathia is a disease which can appear in patients with myasthenia gravis. If patients with MG are adequately neurologically prepared they may undergo aesthetic, functional operation, which leads to improvement in the course of the disease."} {"id": "PMID:1279924", "title": "Effects of acute isovolemic hemodilution and anesthesia on regional function in left ventricular myocardium with compromised coronary blood flow.", "content": "The effects of progressive, isovolemic hemodilution using Dextran 70 and the effect of halothane (0.7, 0.9, 1.1, and 1.3% end-tidal, administered randomly at each level of hemodilution) on global cardiovascular and regional LV contractile functions were investigated in 24 dogs with induced critical constriction of the left anterior descending coronary artery (LAD). Two additional groups of six dogs each (with and without LAD stenosis) not undergoing hemodilution served as time controls. Regional LV contractile function was assessed by sonomicrometry in the flow-compromised apical LAD territory, as well as in three non-compromised LV areas supplied by the left circumflex coronary artery. Regional myocardial function was found to be stable throughout the study period of 4-5 h in both time control groups. Mean arterial and coronary perfusion pressures as well as LV dP/dtmin decreased (P < 0.01) during hemodilution. LV dP/dtmax remained unchanged, and heart rate and LVEDP increased slightly (P < 0.05). Systolic shortening (SS) in the LAD territory was unchanged at a hematocrit (HCT) of 33.5 +/- 0.3% (mean +/- s.e. mean), and decreased marginally at an HCT of 24.2 +/- 0.1% (SS of 17.4 +/- 1.0% as compared to 20.2 +/- 1.6% at critical constriction (CC), P < 0.05). No increase in post-systolic shortening (PSS) occurred in the compromised area. Severe LAD dysfunction was observed in the LAD territory at an HCT of 14.9 +/- 0.1%, as systolic shortening decreased (11.8 +/- 1.1%, P < 0.01 vs CC) and PSS increased (31.2 +/- 3.4%, P < 0.01 vs CC). The effects of hemodilution on global cardiovascular and regional myocardial functions were unaffected by halothane.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of acute isovolemic hemodilution and anesthesia on regional function in left ventricular myocardium with compromised coronary blood flow. The effects of progressive, isovolemic hemodilution using Dextran 70 and the effect of halothane (0.7, 0.9, 1.1, and 1.3% end-tidal, administered randomly at each level of hemodilution) on global cardiovascular and regional LV contractile functions were investigated in 24 dogs with induced critical constriction of the left anterior descending coronary artery (LAD). Two additional groups of six dogs each (with and without LAD stenosis) not undergoing hemodilution served as time controls. Regional LV contractile function was assessed by sonomicrometry in the flow-compromised apical LAD territory, as well as in three non-compromised LV areas supplied by the left circumflex coronary artery. Regional myocardial function was found to be stable throughout the study period of 4-5 h in both time control groups. Mean arterial and coronary perfusion pressures as well as LV dP/dtmin decreased (P < 0.01) during hemodilution. LV dP/dtmax remained unchanged, and heart rate and LVEDP increased slightly (P < 0.05). Systolic shortening (SS) in the LAD territory was unchanged at a hematocrit (HCT) of 33.5 +/- 0.3% (mean +/- s.e. mean), and decreased marginally at an HCT of 24.2 +/- 0.1% (SS of 17.4 +/- 1.0% as compared to 20.2 +/- 1.6% at critical constriction (CC), P < 0.05). No increase in post-systolic shortening (PSS) occurred in the compromised area. Severe LAD dysfunction was observed in the LAD territory at an HCT of 14.9 +/- 0.1%, as systolic shortening decreased (11.8 +/- 1.1%, P < 0.01 vs CC) and PSS increased (31.2 +/- 3.4%, P < 0.01 vs CC). The effects of hemodilution on global cardiovascular and regional myocardial functions were unaffected by halothane.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279925", "title": "Distribution of calcitonin gene-related peptide and substance P-immunoreactive nerve fibers and their correlation in the periodontal ligament of the mouse incisor.", "content": "The distribution of calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive (IR) nerve fibers and their correlation in the periodontal ligament of mouse incisors were examined by indirect immunofluorescence. Both CGRP-IR and SP-IR thin nerve fibers were abundant in the apical and middle third of the periodontal ligament. In the lingual portion of the incisal periodontal ligament, these nerve fibers were localized in the alveolar half of the periodontal ligament and were observed as free nerve endings. No CGRP-IR and SP-IR specialized nerve endings, such as Ruffini-like corpuscles, were observed. In the labial periodontal ligament, CGRP-IR and SP-IR nerve fibers ran along the incisal axis. The distribution of CGRP-IR nerve fibers was very similar to that of SP-IR nerve fibers.", "contents": "Distribution of calcitonin gene-related peptide and substance P-immunoreactive nerve fibers and their correlation in the periodontal ligament of the mouse incisor. The distribution of calcitonin gene-related peptide (CGRP)- and substance P (SP)-immunoreactive (IR) nerve fibers and their correlation in the periodontal ligament of mouse incisors were examined by indirect immunofluorescence. Both CGRP-IR and SP-IR thin nerve fibers were abundant in the apical and middle third of the periodontal ligament. In the lingual portion of the incisal periodontal ligament, these nerve fibers were localized in the alveolar half of the periodontal ligament and were observed as free nerve endings. No CGRP-IR and SP-IR specialized nerve endings, such as Ruffini-like corpuscles, were observed. In the labial periodontal ligament, CGRP-IR and SP-IR nerve fibers ran along the incisal axis. The distribution of CGRP-IR nerve fibers was very similar to that of SP-IR nerve fibers."} {"id": "PMID:1279927", "title": "Time profile of calcium accumulation in hippocampus, striatum and frontoparietal cortex after transient forebrain ischemia in the gerbil.", "content": "The topical and temporal relationship between neuronal injury and calcium loading was investigated in gerbils following bilateral carotid artery occlusion for 5 or 10 min and recirculation times from 15 min to 7 days. The association of histochemically visible calcium deposits with neuronal death was assessed by combining two calcium stains, alizarin red and arsenazo III, with conventional histological techniques. Neuronal calcium accumulation was evaluated morphometrically in the striatum, the frontoparietal cortex and the CA1 and CA4 sectors of the hippocampus. After 5-min ischemia and 1-2 days of recirculation numerous calcium-containing neurons appeared in the CA4 sector but only a few were present in the CA1 sector. After 4 days of recirculation calcium accumulation was visible in the whole CA1 sector and the dorso-lateral part of striate nucleus. After 10-min ischemia calcium accumulation started in these regions, as well as in the cortex, already after 1 day. In the CA1 sector calcium accumulation followed a typical time course: on day 2 only the lateral parts were affected, while on day 4 the whole CA1 neuronal band was calcium positive. The regional distribution of histological lesions matched that of calcium loading and, furthermore, the lesions appeared after a corresponding delay in the respective regions. Morphometric evaluations of calcium staining and histological lesions in the CA1 sector revealed a high correlation, indicating that calcium accumulation and neuronal death are closely associated both topically and temporally. This suggests that disturbances of calcium homeostasis such as those measured by this histochemical technique are the consequence of and not the reason for ischemic cell death.", "contents": "Time profile of calcium accumulation in hippocampus, striatum and frontoparietal cortex after transient forebrain ischemia in the gerbil. The topical and temporal relationship between neuronal injury and calcium loading was investigated in gerbils following bilateral carotid artery occlusion for 5 or 10 min and recirculation times from 15 min to 7 days. The association of histochemically visible calcium deposits with neuronal death was assessed by combining two calcium stains, alizarin red and arsenazo III, with conventional histological techniques. Neuronal calcium accumulation was evaluated morphometrically in the striatum, the frontoparietal cortex and the CA1 and CA4 sectors of the hippocampus. After 5-min ischemia and 1-2 days of recirculation numerous calcium-containing neurons appeared in the CA4 sector but only a few were present in the CA1 sector. After 4 days of recirculation calcium accumulation was visible in the whole CA1 sector and the dorso-lateral part of striate nucleus. After 10-min ischemia calcium accumulation started in these regions, as well as in the cortex, already after 1 day. In the CA1 sector calcium accumulation followed a typical time course: on day 2 only the lateral parts were affected, while on day 4 the whole CA1 neuronal band was calcium positive. The regional distribution of histological lesions matched that of calcium loading and, furthermore, the lesions appeared after a corresponding delay in the respective regions. Morphometric evaluations of calcium staining and histological lesions in the CA1 sector revealed a high correlation, indicating that calcium accumulation and neuronal death are closely associated both topically and temporally. This suggests that disturbances of calcium homeostasis such as those measured by this histochemical technique are the consequence of and not the reason for ischemic cell death."} {"id": "PMID:1279928", "title": "A randomized, double-blind, placebo-controlled study of dextran/pentoxifylline medication in acute acoustic trauma and sudden hearing loss.", "content": "The effectiveness of any therapy in acute acoustic trauma or sudden hearing loss of unknown origin has not been demonstrated convincingly. The assessment is difficult because of a relatively high rate of spontaneous recovery. Nevertheless, many different forms of treatment are recommended. We tested one form, treatment with rheoactive substances, in a prospective, randomized, double-blind trial and compared treatment with (a) infusions of dextran-40 with pentoxifylline, (b) saline infusions with pentoxifylline, and (c) saline infusions with placebo medication. Pure-tone hearing thresholds served as control parameters and were taken before treatment and at 1 and 4 weeks after the onset of therapy. Three hundred eighty-two patients were included in the trial, 331 (87%) could be analyzed, 184 patients were treated because of sudden hearing loss, 147 because of acute acoustic trauma. The three treatment groups were comparable in their basic characteristics including the amount of initial hearing loss. In patients with sudden hearing loss, no significant differences of hearing recovery were detected between the three treatment groups. Hearing recovery was also similar in patients with acute acoustic trauma. A power analysis of the study revealed that possible true treatment differences of a hearing recovery of 10 dB would have lead to significance with a probability of over 90%. It is concluded that there were, in fact, no clinically relevant differences in hearing gains of sudden hearing loss or acute acoustic trauma between treatments with saline infusions together with placebo medication and treatment with dextran-40 and/or pentoxifylline.", "contents": "A randomized, double-blind, placebo-controlled study of dextran/pentoxifylline medication in acute acoustic trauma and sudden hearing loss. The effectiveness of any therapy in acute acoustic trauma or sudden hearing loss of unknown origin has not been demonstrated convincingly. The assessment is difficult because of a relatively high rate of spontaneous recovery. Nevertheless, many different forms of treatment are recommended. We tested one form, treatment with rheoactive substances, in a prospective, randomized, double-blind trial and compared treatment with (a) infusions of dextran-40 with pentoxifylline, (b) saline infusions with pentoxifylline, and (c) saline infusions with placebo medication. Pure-tone hearing thresholds served as control parameters and were taken before treatment and at 1 and 4 weeks after the onset of therapy. Three hundred eighty-two patients were included in the trial, 331 (87%) could be analyzed, 184 patients were treated because of sudden hearing loss, 147 because of acute acoustic trauma. The three treatment groups were comparable in their basic characteristics including the amount of initial hearing loss. In patients with sudden hearing loss, no significant differences of hearing recovery were detected between the three treatment groups. Hearing recovery was also similar in patients with acute acoustic trauma. A power analysis of the study revealed that possible true treatment differences of a hearing recovery of 10 dB would have lead to significance with a probability of over 90%. It is concluded that there were, in fact, no clinically relevant differences in hearing gains of sudden hearing loss or acute acoustic trauma between treatments with saline infusions together with placebo medication and treatment with dextran-40 and/or pentoxifylline."} {"id": "PMID:1279929", "title": "Neochondrogenesis in the septal area after submucous cartilaginous resection.", "content": "The present work was carried out to study cartilaginous repair after subperichondrial resection of the septal cartilage, the fibrous layer of the perichondrium remaining \"in situ\". In these conditions, after granulation tissue formation, both neochondrogenesis and connective tissue differentiation were observed. Neochondrogenesis was found in defect areas next to the resection borders, and connective tissue formation in those further away. The transition zone between both types of newly-formed tissues showed cells with intermediate characteristics of chondrocytes and myofibroblasts. The findings provide safer proof that new chondrocytes and fibroblasts growing after septal cartilage removal originate largely from a common precursor cell either in the fibrous perichondrial layer or in the connective tissue surrounding it. The peculiar topographic distribution of the newly-formed tissues may be explained by the different effects during respiration of mechanical forces on the septal space, which lacks its cartilaginous support, and on the adjacent remaining cartilage, as well as on the borders of both.", "contents": "Neochondrogenesis in the septal area after submucous cartilaginous resection. The present work was carried out to study cartilaginous repair after subperichondrial resection of the septal cartilage, the fibrous layer of the perichondrium remaining \"in situ\". In these conditions, after granulation tissue formation, both neochondrogenesis and connective tissue differentiation were observed. Neochondrogenesis was found in defect areas next to the resection borders, and connective tissue formation in those further away. The transition zone between both types of newly-formed tissues showed cells with intermediate characteristics of chondrocytes and myofibroblasts. The findings provide safer proof that new chondrocytes and fibroblasts growing after septal cartilage removal originate largely from a common precursor cell either in the fibrous perichondrial layer or in the connective tissue surrounding it. The peculiar topographic distribution of the newly-formed tissues may be explained by the different effects during respiration of mechanical forces on the septal space, which lacks its cartilaginous support, and on the adjacent remaining cartilage, as well as on the borders of both."} {"id": "PMID:1279930", "title": "Study on the dye leakage response of nasal mucosa following topical, capsaicin challenge in guinea pigs.", "content": "We examined the serial changes of intravenously applied dye leakage and preliminary examined histamine release into nasal lavage fluid after topical stimulation with capsaicin in guinea pigs. A significant increase in the dye leakage response was detected for 30-40 min, with the maximum response occurring between 5 and 10 min after topical capsaicin stimulation. The dye leakage response to nasal capsaicin challenge was abolished by pretreatment with topical lidocaine, general substance P analogue, topical or general high dosage capsaicin. The dye leakage response to topical capsaicin challenge was significantly reduced following pretreatment with antihistamine, diphenhydramine or atropine sulfate, although it was not affected by pretreatment with an anti-leukotriene, FPL 55712. Topical methacholine challenge did not induce a dye leakage response. An increase in the concentration of histamine in the nasal lavage fluid was noted at 5 min after topical capsaicin challenge. The concentrations of released histamine tended to be positively correlated with those of leaked dye in the nasal lavage fluids. The histamine release induced by topical stimulation with capsaicin tended to be reduced following general and topical pretreatments with high dosage of capsaicin, and was almost completely abolished following atropine pretreatment. From this study it was concluded that nasal capsaicin stimulation can reflexively induce an intravenously applied dye leakage into the nasal cavity, and that C-fiber related cholinergic nerve reflex and histamine release might, at least partially, be related to this response.", "contents": "Study on the dye leakage response of nasal mucosa following topical, capsaicin challenge in guinea pigs. We examined the serial changes of intravenously applied dye leakage and preliminary examined histamine release into nasal lavage fluid after topical stimulation with capsaicin in guinea pigs. A significant increase in the dye leakage response was detected for 30-40 min, with the maximum response occurring between 5 and 10 min after topical capsaicin stimulation. The dye leakage response to nasal capsaicin challenge was abolished by pretreatment with topical lidocaine, general substance P analogue, topical or general high dosage capsaicin. The dye leakage response to topical capsaicin challenge was significantly reduced following pretreatment with antihistamine, diphenhydramine or atropine sulfate, although it was not affected by pretreatment with an anti-leukotriene, FPL 55712. Topical methacholine challenge did not induce a dye leakage response. An increase in the concentration of histamine in the nasal lavage fluid was noted at 5 min after topical capsaicin challenge. The concentrations of released histamine tended to be positively correlated with those of leaked dye in the nasal lavage fluids. The histamine release induced by topical stimulation with capsaicin tended to be reduced following general and topical pretreatments with high dosage of capsaicin, and was almost completely abolished following atropine pretreatment. From this study it was concluded that nasal capsaicin stimulation can reflexively induce an intravenously applied dye leakage into the nasal cavity, and that C-fiber related cholinergic nerve reflex and histamine release might, at least partially, be related to this response."} {"id": "PMID:1279931", "title": "Sialomucin in middle ear cholesteatoma perimatrix.", "content": "Mucosubstance histochemistry of human middle ear cholesteatoma revealed that sialomucins are abundant and sulfomucins present in small amounts in the glandlike structures of the cholesteatoma perimatrix. Based on the study, various glycoproteins were injected into the dermis of the external ear canal and infiltrated into the tympanic membranes of guinea pigs. Tympanic membranes were obtained 7 days later and light- and electron-microscopically studied. Injection of a sialomucin from bovine submaxillary gland resulted in marked proliferation of epidermis and degeneration of the lamina propria. Asialomucin prepared from sialomucin by hydrolysis produced mild thickening of the epidermis but the lamina propria was not degenerated. Fetuin and bovine serum albumin did not cause proliferation of the epidermis. Cholesterol granuloma formed in some of the specimens injected with sialomucin. The presence of sialomucin in cholesteatoma perimatrix and these experimental studies using tympanic membranes of guinea pigs suggests that sialomucins participate in the proliferation of epidermis and degeneration of subepidermal connective tissue in human middle ear cholesteatoma.", "contents": "Sialomucin in middle ear cholesteatoma perimatrix. Mucosubstance histochemistry of human middle ear cholesteatoma revealed that sialomucins are abundant and sulfomucins present in small amounts in the glandlike structures of the cholesteatoma perimatrix. Based on the study, various glycoproteins were injected into the dermis of the external ear canal and infiltrated into the tympanic membranes of guinea pigs. Tympanic membranes were obtained 7 days later and light- and electron-microscopically studied. Injection of a sialomucin from bovine submaxillary gland resulted in marked proliferation of epidermis and degeneration of the lamina propria. Asialomucin prepared from sialomucin by hydrolysis produced mild thickening of the epidermis but the lamina propria was not degenerated. Fetuin and bovine serum albumin did not cause proliferation of the epidermis. Cholesterol granuloma formed in some of the specimens injected with sialomucin. The presence of sialomucin in cholesteatoma perimatrix and these experimental studies using tympanic membranes of guinea pigs suggests that sialomucins participate in the proliferation of epidermis and degeneration of subepidermal connective tissue in human middle ear cholesteatoma."} {"id": "PMID:1279932", "title": "The effect of arachidonic acid metabolites on the ciliary beat frequency of human nasal mucosa in vitro.", "content": "Using computerized microphotometry, we studied the effects of prostaglandin E2 (PGE2), the prostacyclin analog Iloprost, and the thromboxane A2 analog U46619 on the ciliary beat frequency (CBF) of human nasal mucosa. Thirty-two normal subjects underwent nasal cytologic brushing of the inferior meatus to obtain ciliary samples, and a total of 5,640 ciliated cell clusters were analyzed. Each subject served as their own control. PGE2, 10(-10) to 10(-6) M, produced a significant dose dependent increase in CBF of up to 12% versus control. This increase was not significantly inhibited by the addition of the cyclooxygenase inhibitor indomethacin (10(-6) M). Iloprost, 10(-12) to 10(-6) M, also significantly increased CBF by 12.7% at 10(-8) M. This ciliostimulatory effect, however, was abolished by indomethacin. The thromboxane A2 analog, 10(-10) to 10(-6) M, did not significantly effect CBF. The present study demonstrates that a thromboxane A2 analog has no effect on ciliary motility, PGE2 has a direct ciliostimulatory effect, and a prostacyclin analog has a ciliostimulatory effect likely mediated by stimulation of the cyclooxygenase pathway within human cells.", "contents": "The effect of arachidonic acid metabolites on the ciliary beat frequency of human nasal mucosa in vitro. Using computerized microphotometry, we studied the effects of prostaglandin E2 (PGE2), the prostacyclin analog Iloprost, and the thromboxane A2 analog U46619 on the ciliary beat frequency (CBF) of human nasal mucosa. Thirty-two normal subjects underwent nasal cytologic brushing of the inferior meatus to obtain ciliary samples, and a total of 5,640 ciliated cell clusters were analyzed. Each subject served as their own control. PGE2, 10(-10) to 10(-6) M, produced a significant dose dependent increase in CBF of up to 12% versus control. This increase was not significantly inhibited by the addition of the cyclooxygenase inhibitor indomethacin (10(-6) M). Iloprost, 10(-12) to 10(-6) M, also significantly increased CBF by 12.7% at 10(-8) M. This ciliostimulatory effect, however, was abolished by indomethacin. The thromboxane A2 analog, 10(-10) to 10(-6) M, did not significantly effect CBF. The present study demonstrates that a thromboxane A2 analog has no effect on ciliary motility, PGE2 has a direct ciliostimulatory effect, and a prostacyclin analog has a ciliostimulatory effect likely mediated by stimulation of the cyclooxygenase pathway within human cells."} {"id": "PMID:1279933", "title": "Effects of capsaicin desensitization on nasal allergy-like symptoms and histamine release in the nose induced by toluene diisocyanate in guinea pigs.", "content": "Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like symptoms of sneezing and watery rhinorrhea and decreased the histamine content of the nasal mucosa in guinea pigs. However, in the animals pretreated with capsaicin (capsaicin desensitization) before sensitization with TDI, nasal allergy-like symptoms were not induced. Capsaicin desensitization also inhibited histamine release in the nasal mucosa induced by TDI. These findings suggest that antidromic impulses of capsaicin-sensitive sensory nerves stimulated by TDI cause histamine release from mast cells in the nasal mucosa, resulting in nasal discharge and sneezing in guinea pigs. Thus neurogenic inflammation via an axon reflex in the nose may contribute to the pathogenesis of vasomotor rhinitis.", "contents": "Effects of capsaicin desensitization on nasal allergy-like symptoms and histamine release in the nose induced by toluene diisocyanate in guinea pigs. Intranasal application of toluene diisocyanate (TDI) induced nasal allergy-like symptoms of sneezing and watery rhinorrhea and decreased the histamine content of the nasal mucosa in guinea pigs. However, in the animals pretreated with capsaicin (capsaicin desensitization) before sensitization with TDI, nasal allergy-like symptoms were not induced. Capsaicin desensitization also inhibited histamine release in the nasal mucosa induced by TDI. These findings suggest that antidromic impulses of capsaicin-sensitive sensory nerves stimulated by TDI cause histamine release from mast cells in the nasal mucosa, resulting in nasal discharge and sneezing in guinea pigs. Thus neurogenic inflammation via an axon reflex in the nose may contribute to the pathogenesis of vasomotor rhinitis."} {"id": "PMID:1279934", "title": "Long-term hypoxia induces changes in the substance P immunoreactivity pattern in laryngeal nerve paraganglia.", "content": "We previously showed that long-term hypoxia increases the dopamine content in rat laryngeal nerve paraganglia. In the present study paraganglia of rats exposed to hypoxia (10 +/- 0.5% O2) for 14 days were examined immunohistochemically to detect changes in the expression of neuropeptides and catecholamine-synthesizing enzymes. Hypoxia induced an intense cellular substance P (SP)-like immunoreactivity (LI) in some paraganglia and an increase in the number of stromal nerve fibers showing SP-LI in others. The patterns of tyrosine hydroxylase-, dopamine-beta-hydroxylase-, phenylethanolamine-N-methyltransferase-, vasoactive intestinal polypeptide-, neuropeptide-Y and calcitonin gene-related peptide-LI were not changed in response to hypoxia. The results show that hypoxia induces changes in the pattern of SP immunoreactivity in laryngeal nerve paraganglia and may indicate that SP plays a role in the regulation of catecholamine metabolism in this tissue.", "contents": "Long-term hypoxia induces changes in the substance P immunoreactivity pattern in laryngeal nerve paraganglia. We previously showed that long-term hypoxia increases the dopamine content in rat laryngeal nerve paraganglia. In the present study paraganglia of rats exposed to hypoxia (10 +/- 0.5% O2) for 14 days were examined immunohistochemically to detect changes in the expression of neuropeptides and catecholamine-synthesizing enzymes. Hypoxia induced an intense cellular substance P (SP)-like immunoreactivity (LI) in some paraganglia and an increase in the number of stromal nerve fibers showing SP-LI in others. The patterns of tyrosine hydroxylase-, dopamine-beta-hydroxylase-, phenylethanolamine-N-methyltransferase-, vasoactive intestinal polypeptide-, neuropeptide-Y and calcitonin gene-related peptide-LI were not changed in response to hypoxia. The results show that hypoxia induces changes in the pattern of SP immunoreactivity in laryngeal nerve paraganglia and may indicate that SP plays a role in the regulation of catecholamine metabolism in this tissue."} {"id": "PMID:1279935", "title": "A case of mixed-type dysgerminoma with a high serum concentration of both human chorionic gonadotropin and alpha-fetoprotein in a child.", "content": "Dysgerminoma is divided into two types: pure and mixed. The mixed type is related to other various elements of germ cell tumors. We experienced a case of mixed type dysgerminoma with a high serum concentration of both human chorionic gonadotropin and alpha-fetoprotein. The patient was a 6 year old girl who was admitted to the Hamamatsu University School of Medicine with an abdominal mass. Laboratory investigations revealed elevated serum alpha-fetoprotein and high concentration of serum beta-human chorionic gonadotropin. The tumor originated from the left ovary. The histopathological diagnosis was dysgerminoma. Serum human chorionic gonadotropin and alpha-fetoprotein levels were useful markers in monitoring the response to treatment in this patient.", "contents": "A case of mixed-type dysgerminoma with a high serum concentration of both human chorionic gonadotropin and alpha-fetoprotein in a child. Dysgerminoma is divided into two types: pure and mixed. The mixed type is related to other various elements of germ cell tumors. We experienced a case of mixed type dysgerminoma with a high serum concentration of both human chorionic gonadotropin and alpha-fetoprotein. The patient was a 6 year old girl who was admitted to the Hamamatsu University School of Medicine with an abdominal mass. Laboratory investigations revealed elevated serum alpha-fetoprotein and high concentration of serum beta-human chorionic gonadotropin. The tumor originated from the left ovary. The histopathological diagnosis was dysgerminoma. Serum human chorionic gonadotropin and alpha-fetoprotein levels were useful markers in monitoring the response to treatment in this patient."} {"id": "PMID:1279936", "title": "[Studies on polypeptides. IX. Synthesis and antigen specificity of pre-S region fragments of hepatitis B surface antigen].", "content": "Seven peptide fragments of HBsAg Pre-S region have been synthesized by liquid phase and solid phase methods. All peptide fragments were linked to protein carrier by carbodiimide and glutaraldehyde methods. The antigen specificity of the peptide--protein conjugates was assayed by anti-HBsAg polyclonal antibodies and anti--\"a\" monoclonal antibody. P1 and P5 were found to have higher antigen specificity.", "contents": "[Studies on polypeptides. IX. Synthesis and antigen specificity of pre-S region fragments of hepatitis B surface antigen]. Seven peptide fragments of HBsAg Pre-S region have been synthesized by liquid phase and solid phase methods. All peptide fragments were linked to protein carrier by carbodiimide and glutaraldehyde methods. The antigen specificity of the peptide--protein conjugates was assayed by anti-HBsAg polyclonal antibodies and anti--\"a\" monoclonal antibody. P1 and P5 were found to have higher antigen specificity."} {"id": "PMID:1279937", "title": "[Effect of carboxyethylgermanium sesquioxide on cultured normal neonatal rat myocardial cells and cells injured by isoproterenol].", "content": "The effect of carboxyethylgermanium sesquioxide (Ge-132) on cultured neonatal rat myocytes and isoproterenol injured myocytes was studied. The results showed that Ge-132 (0.01 mmol.L-1 and 1 mmol.L-1) increased the incorporation of both [3H]-TdR and [14C]-UR, reduced the membrane lipid fluidity and inhibited the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Exposure of the myocytes to isoproterenol 0.5 mmol.L-1 for 6 hours resulted in 5-fold release of LDH compared with the control. All myocytes ceased beating. Ultrastructurally, severe sarcolemmal and mitochondrial damage was evident. When the cells were pretreated with Ge-132 before the addition of isoproterenol, the increased LDH release was inhibited significantly, and preservation of beat and ultrastructure of myocytes was observed. In addition, the activity of superoxide dismutase (SOD) was elevated by Ge-132. All the effects of Ge-132 were dose-related. The results indicate that Ge-132 may improve the metabolism of cultured neonatal rat myocytes and protect myocytes from isoproterenol-induced injury.", "contents": "[Effect of carboxyethylgermanium sesquioxide on cultured normal neonatal rat myocardial cells and cells injured by isoproterenol]. The effect of carboxyethylgermanium sesquioxide (Ge-132) on cultured neonatal rat myocytes and isoproterenol injured myocytes was studied. The results showed that Ge-132 (0.01 mmol.L-1 and 1 mmol.L-1) increased the incorporation of both [3H]-TdR and [14C]-UR, reduced the membrane lipid fluidity and inhibited the release of the cytoplasmic enzyme lactate dehydrogenase (LDH). Exposure of the myocytes to isoproterenol 0.5 mmol.L-1 for 6 hours resulted in 5-fold release of LDH compared with the control. All myocytes ceased beating. Ultrastructurally, severe sarcolemmal and mitochondrial damage was evident. When the cells were pretreated with Ge-132 before the addition of isoproterenol, the increased LDH release was inhibited significantly, and preservation of beat and ultrastructure of myocytes was observed. In addition, the activity of superoxide dismutase (SOD) was elevated by Ge-132. All the effects of Ge-132 were dose-related. The results indicate that Ge-132 may improve the metabolism of cultured neonatal rat myocytes and protect myocytes from isoproterenol-induced injury."} {"id": "PMID:1279938", "title": "Inhibitory effects of tetrandrine on Bay k 8644-stimulated contraction of isolated rabbit aortic strips.", "content": "In the presence of KCl 19 mmol.L-1, calcium agonist Bay k 8644 0.47 mumol.L-1 elicited a strong contraction of isolated rabbit aortic strips, and this contraction was concentration-dependently inhibited by tetrandrine; but this antagonism was noncompetitive. Calcium ionophore calcimycin evoked contraction was markedly depressed by tetrandrine. The results suggested that tetrandrine might not only inhibit transmembrane influx of calcium via potential-dependent channels but also interfere with other processes related to calcium.", "contents": "Inhibitory effects of tetrandrine on Bay k 8644-stimulated contraction of isolated rabbit aortic strips. In the presence of KCl 19 mmol.L-1, calcium agonist Bay k 8644 0.47 mumol.L-1 elicited a strong contraction of isolated rabbit aortic strips, and this contraction was concentration-dependently inhibited by tetrandrine; but this antagonism was noncompetitive. Calcium ionophore calcimycin evoked contraction was markedly depressed by tetrandrine. The results suggested that tetrandrine might not only inhibit transmembrane influx of calcium via potential-dependent channels but also interfere with other processes related to calcium."} {"id": "PMID:1279939", "title": "Semi-differential voltammetry with carbon fiber electrodes for in vivo determination of monoamine metabolites and ascorbic acid in rat corpus striatum.", "content": "Carbon fiber electrodes combined with semi-differential voltammetry were used to determine endogenous monoamine metabolites and ascorbic acid (AA). These electrodes treated by a new electrochemical procedure (30 microA for 30 s, then -2 V for 10 s) showed a significant improvement on the sensitivity and selectivity. In the rat corpus striatum, these electrodes allowed a distinct separation and continuous detection of AA, 3, 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) simultaneously. The normal striatal levels of AA, DOPAC, and 5-HIAA were found to be 168.2 +/- 19.5, 21.4 +/- 3.9, and 3.3 +/- 0.5 mumol.L-1. Our method is credible for detecting the changes of monoamine metabolite contents induced by pharmacologic manipulations.", "contents": "Semi-differential voltammetry with carbon fiber electrodes for in vivo determination of monoamine metabolites and ascorbic acid in rat corpus striatum. Carbon fiber electrodes combined with semi-differential voltammetry were used to determine endogenous monoamine metabolites and ascorbic acid (AA). These electrodes treated by a new electrochemical procedure (30 microA for 30 s, then -2 V for 10 s) showed a significant improvement on the sensitivity and selectivity. In the rat corpus striatum, these electrodes allowed a distinct separation and continuous detection of AA, 3, 4-dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIAA) simultaneously. The normal striatal levels of AA, DOPAC, and 5-HIAA were found to be 168.2 +/- 19.5, 21.4 +/- 3.9, and 3.3 +/- 0.5 mumol.L-1. Our method is credible for detecting the changes of monoamine metabolite contents induced by pharmacologic manipulations."} {"id": "PMID:1279940", "title": "Different ion channel mechanisms between low concentrations of capsaicin and high concentrations of capsaicin and nicotine regarding peptide release from pulmonary afferents.", "content": "Vagal nerve stimulation (1 Hz for 1 min), capsaicin (10(-8) M and 10(-6) M), resiniferatoxin (3 x 10(-10) M) and nicotine (10(-4) M) evoked a non-cholinergic bronchoconstriction in the isolated perfused guinea-pig lung preparation. Simultaneously there was an increase in the perfusate levels of calcitonin gene-related peptide-like immunoreactivity, suggesting release from sensory nerves. Both the bronchoconstriction and peptide release evoked by a low concentration of capsaicin (10(-8) M) and that evoked by nerve stimulation were depressed by tetrodotoxin, suggesting involvement of Na+ channel dependent depolarization. Since the effects of capsaicin (10(-8) M) and vagal nerve stimulation were inhibited by omega-conotoxin but not influenced by nifedipine, the Ca(2+)-channel dependent is probably of N-type. Furthermore, the capsaicin analogue resiniferatoxin also evoked omega-conotoxin sensitive peptide release and bronchoconstriction. At the higher capsaicin concentration (10(-6) M), the functional response was only slightly inhibited by omega-conotoxin or tetrodotoxin indicating that capsaicin at this concentration evoked peptide release and functional effects through other mechanisms, probably involving Ca2+ fluxes in the non-selective cation channel associated with the proposed capsaicin receptor. The nicotine (10(-4) M) evoked peptide release and bronchoconstriction were only marginally influenced by omega-conotoxin or tetrodotoxin. It is concluded that the ion-channel mechanisms underlying the peptide releasing properties of antidromic nerve stimulation and low concentrations of capsaicin are similar and depend on action potential propagation, whereas capsaicin in high, toxic concentration and nicotine mainly act via receptor operated channels.", "contents": "Different ion channel mechanisms between low concentrations of capsaicin and high concentrations of capsaicin and nicotine regarding peptide release from pulmonary afferents. Vagal nerve stimulation (1 Hz for 1 min), capsaicin (10(-8) M and 10(-6) M), resiniferatoxin (3 x 10(-10) M) and nicotine (10(-4) M) evoked a non-cholinergic bronchoconstriction in the isolated perfused guinea-pig lung preparation. Simultaneously there was an increase in the perfusate levels of calcitonin gene-related peptide-like immunoreactivity, suggesting release from sensory nerves. Both the bronchoconstriction and peptide release evoked by a low concentration of capsaicin (10(-8) M) and that evoked by nerve stimulation were depressed by tetrodotoxin, suggesting involvement of Na+ channel dependent depolarization. Since the effects of capsaicin (10(-8) M) and vagal nerve stimulation were inhibited by omega-conotoxin but not influenced by nifedipine, the Ca(2+)-channel dependent is probably of N-type. Furthermore, the capsaicin analogue resiniferatoxin also evoked omega-conotoxin sensitive peptide release and bronchoconstriction. At the higher capsaicin concentration (10(-6) M), the functional response was only slightly inhibited by omega-conotoxin or tetrodotoxin indicating that capsaicin at this concentration evoked peptide release and functional effects through other mechanisms, probably involving Ca2+ fluxes in the non-selective cation channel associated with the proposed capsaicin receptor. The nicotine (10(-4) M) evoked peptide release and bronchoconstriction were only marginally influenced by omega-conotoxin or tetrodotoxin. It is concluded that the ion-channel mechanisms underlying the peptide releasing properties of antidromic nerve stimulation and low concentrations of capsaicin are similar and depend on action potential propagation, whereas capsaicin in high, toxic concentration and nicotine mainly act via receptor operated channels."} {"id": "PMID:1279941", "title": "Block of potassium outward currents in the crayfish stretch receptor neurons by 4-aminopyridine, tetraethylammonium chloride and some other chemical substances.", "content": "The effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the outward potassium currents in the rapidly and slowly adapting stretch receptor neurons (SRNs) of the crayfish (Pacifastacus leniusculus) were studied using a two micro-electrode voltage-clamp technique. The leakage current was not affected by either 4-AP or TEA. External 4-AP blocked the peak outward current in a dose-dependent manner (1:1 stoichiometry) with an apparent dissociation constant (Kd) of 2.3 +/- 0.2 mM (mean +/- SEM) in the slowly and 1.4 +/- 0.2 mM in the rapidly adapting SRN, the block being voltage dependent. External application of TEA resulted in a block of the steady state current enhancing the transient characteristics of the current response. The block appeared to deviate from a 1:1 stoichiometry and the apparent Kd for TEA was 9.6 +/- 3.4 mM with a cooperativity factor n = 0.43 +/- 0.03 in the slowly adapting SRN and 34.5 +/- 9.2 mM and 0.37 +/- 0.03 respectively in the rapidly adapting SRN. Low Ca2+, apamin and charybdotoxin, which are known to block Ca(2+)-dependent K-currents, had no effects on the outward current as was also the case with catechol. It is concluded that the different effects of TEA and 4-AP on the outward current in the two types of SRNs can be explained by the presence of at least two, probably heteromultimeric, channel populations having similar sensitivity to 4-AP but different sensitivity to TEA. One channel has a high affinity (Kd = 0.8-1.6 mM) for TEA and the other a low affinity (Kd = 173-213 mM) for TEA. The low-affinity channel seems to dominate in the slowly adapting SRN while both channels are equally common in the rapidly adapting SRN. Further, the present results do not support the existence of a macroscopic Ca(2+)-dependent K+ current in the SRNs.", "contents": "Block of potassium outward currents in the crayfish stretch receptor neurons by 4-aminopyridine, tetraethylammonium chloride and some other chemical substances. The effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on the outward potassium currents in the rapidly and slowly adapting stretch receptor neurons (SRNs) of the crayfish (Pacifastacus leniusculus) were studied using a two micro-electrode voltage-clamp technique. The leakage current was not affected by either 4-AP or TEA. External 4-AP blocked the peak outward current in a dose-dependent manner (1:1 stoichiometry) with an apparent dissociation constant (Kd) of 2.3 +/- 0.2 mM (mean +/- SEM) in the slowly and 1.4 +/- 0.2 mM in the rapidly adapting SRN, the block being voltage dependent. External application of TEA resulted in a block of the steady state current enhancing the transient characteristics of the current response. The block appeared to deviate from a 1:1 stoichiometry and the apparent Kd for TEA was 9.6 +/- 3.4 mM with a cooperativity factor n = 0.43 +/- 0.03 in the slowly adapting SRN and 34.5 +/- 9.2 mM and 0.37 +/- 0.03 respectively in the rapidly adapting SRN. Low Ca2+, apamin and charybdotoxin, which are known to block Ca(2+)-dependent K-currents, had no effects on the outward current as was also the case with catechol. It is concluded that the different effects of TEA and 4-AP on the outward current in the two types of SRNs can be explained by the presence of at least two, probably heteromultimeric, channel populations having similar sensitivity to 4-AP but different sensitivity to TEA. One channel has a high affinity (Kd = 0.8-1.6 mM) for TEA and the other a low affinity (Kd = 173-213 mM) for TEA. The low-affinity channel seems to dominate in the slowly adapting SRN while both channels are equally common in the rapidly adapting SRN. Further, the present results do not support the existence of a macroscopic Ca(2+)-dependent K+ current in the SRNs."} {"id": "PMID:1279942", "title": "Functional effects of a hyperpolarization-activated membrane current in the lobster stretch receptor neurone.", "content": "The functional effects of a hyperpolarization-activated membrane current (IQ) in the slowly adapting lobster stretch receptor neurone were investigated. From comparisons between changes in membrane excitability due to blockage of IQ by Cs+, in normally impaled and native unimpaled (Edman et al. 1987 b) cells, it could be concluded that the resting voltage of native cells is distinctly more negative than -65 mV (average membrane voltage of impaled cells) and, therefore, under the control of an activated IQ. Starting from this conclusion, impaled cells were polarized to holding (resting) voltages around -75 mV and their polarization and excitability properties studied after tetanic impulse activity and variation of various external influences (K+, pH, temperature), both in control conditions and after blockage of IQ by 2 mM Cs+. It was found that an unblocked IQ (a) greatly accelerates the initial (90%) decay of post-tetanic hyperpolarization, and (b) depresses distinctly any polarization and excitability alterations due to increases in extracellular K+ concentration (from 2.5 to 10 mM), variations in extracellular pH (between 6.4 and 8.6), and changes in temperature (between 14 and 24 degrees C). It was inferred that in well polarized cells, IQ plays a role as a stabilizer of membrane polarization and excitability in conditions of varying external influences. From a model study of IQ it could be concluded that, with its slow dynamic responses, the current is well adapted to its functional purposes and to the rather slow homeostatic effects of the cell's Na-K pump.", "contents": "Functional effects of a hyperpolarization-activated membrane current in the lobster stretch receptor neurone. The functional effects of a hyperpolarization-activated membrane current (IQ) in the slowly adapting lobster stretch receptor neurone were investigated. From comparisons between changes in membrane excitability due to blockage of IQ by Cs+, in normally impaled and native unimpaled (Edman et al. 1987 b) cells, it could be concluded that the resting voltage of native cells is distinctly more negative than -65 mV (average membrane voltage of impaled cells) and, therefore, under the control of an activated IQ. Starting from this conclusion, impaled cells were polarized to holding (resting) voltages around -75 mV and their polarization and excitability properties studied after tetanic impulse activity and variation of various external influences (K+, pH, temperature), both in control conditions and after blockage of IQ by 2 mM Cs+. It was found that an unblocked IQ (a) greatly accelerates the initial (90%) decay of post-tetanic hyperpolarization, and (b) depresses distinctly any polarization and excitability alterations due to increases in extracellular K+ concentration (from 2.5 to 10 mM), variations in extracellular pH (between 6.4 and 8.6), and changes in temperature (between 14 and 24 degrees C). It was inferred that in well polarized cells, IQ plays a role as a stabilizer of membrane polarization and excitability in conditions of varying external influences. From a model study of IQ it could be concluded that, with its slow dynamic responses, the current is well adapted to its functional purposes and to the rather slow homeostatic effects of the cell's Na-K pump."} {"id": "PMID:1279943", "title": "Establishment and characterization of a cell line, KaMi, from human lung large cell carcinoma.", "content": "A cell line of human lung large cell carcinoma (LCC) was established directly from the metastatic skin tumor tissue. The clinical course of the patient who carried this carcinoma was peculiar; generalized lymphadenopathy, histologically resembling Hodgkin's disease, was found as the first clinical symptom. The lung tumor was not discovered until the time of autopsy. This cell line (KaMi) grew adherent to culture vessels with the population doubling time of 20.6h, formed colonies in soft agars with efficiency of 22.6%, and formed tumors in athymic nude mice. The authenticity of KaMi was confirmed by chromosomal analysis and isoenzyme patterns. KaMi cells bore a strong resemblance to the original tumor cells which were composed of small spindle cells, large polygonal cells, and multinucleated giant cells. Immunohistochemically, KaMi cells showed a weak tendency to differentiate to squamous cells, and these immunohistochemical reactivities were almost compatible to those of the original tumor cells, but ultrastructurally, KaMi cells were more immature than the original ones. Treatment with several reagents could not augment a differentiation of KaMi cells. Cytokeratin profiles showed a tendency of squamous cell differentiation. KaMi cells may aid in elucidating the pathogenesis and biology of LCC and its relationship to other lung tumors.", "contents": "Establishment and characterization of a cell line, KaMi, from human lung large cell carcinoma. A cell line of human lung large cell carcinoma (LCC) was established directly from the metastatic skin tumor tissue. The clinical course of the patient who carried this carcinoma was peculiar; generalized lymphadenopathy, histologically resembling Hodgkin's disease, was found as the first clinical symptom. The lung tumor was not discovered until the time of autopsy. This cell line (KaMi) grew adherent to culture vessels with the population doubling time of 20.6h, formed colonies in soft agars with efficiency of 22.6%, and formed tumors in athymic nude mice. The authenticity of KaMi was confirmed by chromosomal analysis and isoenzyme patterns. KaMi cells bore a strong resemblance to the original tumor cells which were composed of small spindle cells, large polygonal cells, and multinucleated giant cells. Immunohistochemically, KaMi cells showed a weak tendency to differentiate to squamous cells, and these immunohistochemical reactivities were almost compatible to those of the original tumor cells, but ultrastructurally, KaMi cells were more immature than the original ones. Treatment with several reagents could not augment a differentiation of KaMi cells. Cytokeratin profiles showed a tendency of squamous cell differentiation. KaMi cells may aid in elucidating the pathogenesis and biology of LCC and its relationship to other lung tumors."} {"id": "PMID:1279944", "title": "Enhanced expression of complement regulatory proteins on thyroid epithelial cells of Graves' disease.", "content": "Cytotoxic anti-thyroid microsomal autoantibodies are highly prevalent in sera of patients with Graves' disease, but in Graves' disease thyroid tissues rarely show destructive changes. We postulated that this might be due to membrane-associated complement regulatory proteins which protect target cells from injury by complement activation. We, therefore, investigated the expression of membrane attack complex inhibitory factor (MACIF) and decay accelerating factor (DAF) in the thyroid tissues from patients with Graves' disease, Hashimoto's thyroiditis, thyroid adenocarcinoma and normal human thyroid tissues. We found a high level of expression of MACIF and DAF in Graves' thyroid tissues. Using the membrane immunofluorescence and cell-ELISA techniques, we also investigated the factors which enhanced the MACIF and DAF expression in cultured thyroid cells. Thyroid stimulating hormone, phorbol 12, 13-dibutyrate and thyroid stimulating autoantibody enhanced the MACIF and DAF expression. These findings suggest that the membrane complement regulatory proteins increase in response to the thyroid stimulating factors such as thyroid stimulating autoantibody in Graves' disease and that this increase then protects the cells from damage due to complement activation by thyroid autoantibodies.", "contents": "Enhanced expression of complement regulatory proteins on thyroid epithelial cells of Graves' disease. Cytotoxic anti-thyroid microsomal autoantibodies are highly prevalent in sera of patients with Graves' disease, but in Graves' disease thyroid tissues rarely show destructive changes. We postulated that this might be due to membrane-associated complement regulatory proteins which protect target cells from injury by complement activation. We, therefore, investigated the expression of membrane attack complex inhibitory factor (MACIF) and decay accelerating factor (DAF) in the thyroid tissues from patients with Graves' disease, Hashimoto's thyroiditis, thyroid adenocarcinoma and normal human thyroid tissues. We found a high level of expression of MACIF and DAF in Graves' thyroid tissues. Using the membrane immunofluorescence and cell-ELISA techniques, we also investigated the factors which enhanced the MACIF and DAF expression in cultured thyroid cells. Thyroid stimulating hormone, phorbol 12, 13-dibutyrate and thyroid stimulating autoantibody enhanced the MACIF and DAF expression. These findings suggest that the membrane complement regulatory proteins increase in response to the thyroid stimulating factors such as thyroid stimulating autoantibody in Graves' disease and that this increase then protects the cells from damage due to complement activation by thyroid autoantibodies."} {"id": "PMID:1279945", "title": "Hepatitis C virus antibody titration in patients with chronic hepatitis C, before and after interferon treatment.", "content": "We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment.", "contents": "Hepatitis C virus antibody titration in patients with chronic hepatitis C, before and after interferon treatment. We measured hepatitis C virus antibody titers in 13 patients with chronic hepatitis C to determine whether titration of hepatitis C virus antibody was useful or not, to predict and evaluate the efficacy of interferon (IFN) treatment. During administration of IFN, hepatitis C virus titers declined in all patients. Antibody titers performed before treatment as well as just at the end of treatment did not correlate with change of the alanine aminotransferase levels during administration of IFN. Antibody titers declined continuously after treatment in 5 patients with normal alanine amino-transferase levels for over 6 months after discontinuation of IFN. Antibody titers rose again in 6 patients whose alanine aminotransferase levels fluctuated after treatment. An exceptional pattern of change occurred in 2 patients whose antibody titers declined continuously although their alanine aminotransferase levels fluctuated after treatment. Repeated titration of hepatitis C virus antibody appears to be useful for evaluating the long-term efficacy of IFN treatment."} {"id": "PMID:1279946", "title": "Detection by western blotting of an antibody to the hepatitis C virus E1 envelope protein in sera of patients with chronic liver disease.", "content": "We detected an antibody to HCV envelope protein (E1) in sera of patients with HCV-related chronic liver diseases (20 patients with chronic hepatitis and 5 patients with liver cirrhosis) by Western blotting using the fusion protein of E1 envelope protein and beta-galactosidase as an antigen. The antibody to HCV E1 (anti-HCV E1) was detected in 8 (42%) of 19 patients positive for HCV-RNA (16 were positive and 3 were negative for antibody to C100-3) and in 1 (17%) of 6 patients negative for HCV-RNA but positive for antibody to C100-3. HCV-RNA was detected in 8 (89%) of 9 anti-HCV E1 positive sera. The value of alanine aminotransferase was significantly higher in patients positive for anti-HCV E1 than in patients negative for the antibody. Although an antibody to the envelope protein of HCV is suspected to be one of the candidates of virus-neutralizing antibodies, our results suggest this hypothesis appears to be unlikely.", "contents": "Detection by western blotting of an antibody to the hepatitis C virus E1 envelope protein in sera of patients with chronic liver disease. We detected an antibody to HCV envelope protein (E1) in sera of patients with HCV-related chronic liver diseases (20 patients with chronic hepatitis and 5 patients with liver cirrhosis) by Western blotting using the fusion protein of E1 envelope protein and beta-galactosidase as an antigen. The antibody to HCV E1 (anti-HCV E1) was detected in 8 (42%) of 19 patients positive for HCV-RNA (16 were positive and 3 were negative for antibody to C100-3) and in 1 (17%) of 6 patients negative for HCV-RNA but positive for antibody to C100-3. HCV-RNA was detected in 8 (89%) of 9 anti-HCV E1 positive sera. The value of alanine aminotransferase was significantly higher in patients positive for anti-HCV E1 than in patients negative for the antibody. Although an antibody to the envelope protein of HCV is suspected to be one of the candidates of virus-neutralizing antibodies, our results suggest this hypothesis appears to be unlikely."} {"id": "PMID:1279948", "title": "[Preoperative estimate of the weight of prostatic adenoma using abdominal echography].", "content": "Using a sample of 41 patients, diagnosed with prostate adenoma, an estimate was made on the degree of correlation between the weight of the adenoma as predicted through abdominal ultrasound scan (x) and the actual weight after surgical removal (y). An experimental principle or mathematical formula has been worked out to translate that correlation and it allows the urologist to appraise the adenoma's actual weight as related to the ultrasound scan weight. The degree of correlation between the ultrasound-estimated weight and the actual weight was high (0.85) and statistically significant (p < 0.01). The experimental principle of mathematical formula which will allow the urologist to make a closer approximation to the actual weight of adenomas studied by ultrasound was y = 0.93 * x + 4.7.", "contents": "[Preoperative estimate of the weight of prostatic adenoma using abdominal echography]. Using a sample of 41 patients, diagnosed with prostate adenoma, an estimate was made on the degree of correlation between the weight of the adenoma as predicted through abdominal ultrasound scan (x) and the actual weight after surgical removal (y). An experimental principle or mathematical formula has been worked out to translate that correlation and it allows the urologist to appraise the adenoma's actual weight as related to the ultrasound scan weight. The degree of correlation between the ultrasound-estimated weight and the actual weight was high (0.85) and statistically significant (p < 0.01). The experimental principle of mathematical formula which will allow the urologist to make a closer approximation to the actual weight of adenomas studied by ultrasound was y = 0.93 * x + 4.7."} {"id": "PMID:1279949", "title": "Ion channels for the mechano-electrical transduction and efferent synapse of the hair cell.", "content": "Auditory and vestibular information is applied to the hair cell hair bundle as mechanical energy, and is transduced into electrical energy by gating ion channels. The m-e.t. channel has a unitary conductance of 50 pS and a broad selectivity to monovalent cations and to divalent cations. Ca ions are the most permeable through the channel. The angular displacement of the hair bundle is the primary gating factor. Circumstantial evidence indicates the possibility of the direct gating of channels by the membrane deformation itself. The transduction potential activates voltage gated Ca channel and leads to the release of neurotransmitters which activate afferent neurones. Cholinergic muscarinic receptors likely mediate the inhibitory efferent innervation to the hair cell.", "contents": "Ion channels for the mechano-electrical transduction and efferent synapse of the hair cell. Auditory and vestibular information is applied to the hair cell hair bundle as mechanical energy, and is transduced into electrical energy by gating ion channels. The m-e.t. channel has a unitary conductance of 50 pS and a broad selectivity to monovalent cations and to divalent cations. Ca ions are the most permeable through the channel. The angular displacement of the hair bundle is the primary gating factor. Circumstantial evidence indicates the possibility of the direct gating of channels by the membrane deformation itself. The transduction potential activates voltage gated Ca channel and leads to the release of neurotransmitters which activate afferent neurones. Cholinergic muscarinic receptors likely mediate the inhibitory efferent innervation to the hair cell."} {"id": "PMID:1279947", "title": "Nerve growth factor chromatin receptor and cell surface receptor-regulated growth of melanocytes and nevus cells.", "content": "RNA synthesis in melanocytes and nevus cells, and the proliferation of those cells in the presence of nerve growth factor (NGF) and 12-0-tetradecanoyl-phorbol-13-acetate (TPA), were found to correlate with the amount of NGF bound to the chromatin versus the total internalized NGF (n/c NGF = nuclear/cellular ration). In nevus cells and in melanocytes of the early passages (n/c NGF = 0.16-0.18), NGF slightly activated RNA synthesis but was without any effect on cell growth. At passage 5-6 of melanocytes (n/c NGF = 0.88), NGF inhibited RNA synthesis, which led to inhibition of cell growth. Removal of TPA from the culture of nevus cells resulted in increased n/c NGF ratio and in a switch from activatory to inhibitory action of NGF. The possibility that the cell surface receptor mediated the stimulatory effect of NGF and may antagonize the chromatin receptor-mediated inhibitory effect of NGF of melanocyte and nevus cell growth is discussed.", "contents": "Nerve growth factor chromatin receptor and cell surface receptor-regulated growth of melanocytes and nevus cells. RNA synthesis in melanocytes and nevus cells, and the proliferation of those cells in the presence of nerve growth factor (NGF) and 12-0-tetradecanoyl-phorbol-13-acetate (TPA), were found to correlate with the amount of NGF bound to the chromatin versus the total internalized NGF (n/c NGF = nuclear/cellular ration). In nevus cells and in melanocytes of the early passages (n/c NGF = 0.16-0.18), NGF slightly activated RNA synthesis but was without any effect on cell growth. At passage 5-6 of melanocytes (n/c NGF = 0.88), NGF inhibited RNA synthesis, which led to inhibition of cell growth. Removal of TPA from the culture of nevus cells resulted in increased n/c NGF ratio and in a switch from activatory to inhibitory action of NGF. The possibility that the cell surface receptor mediated the stimulatory effect of NGF and may antagonize the chromatin receptor-mediated inhibitory effect of NGF of melanocyte and nevus cell growth is discussed."} {"id": "PMID:1279952", "title": "Control of angiogenesis by heparin and other sulfated polysaccharides.", "content": "Heparin and its related polysaccharides are revealed to have important new functions as regulators of blood vessel growth and regression. This regulatory activity may be explained in part by at least five mechanisms in which heparin and heparan sulfate interact with peptide growth factors: (1) Heparin and heparan sulfate have a high affinity for angiogenic growth factors such as the fibroblast growth factors and VEGF, as well as for angiogenic inhibitors such as thrombospondin and platelet factor 4. (2) Heparin and its related polysaccharides stabilize bFGF and other growth factors. (3) FGFs and thrombospondin are stored in the extracellular matrix bound to heparan sulfate; fragments of heparin or heparan sulfate may act as natural chaperones to shuttle bFGF or other growth factors to different cellular compartments. (5) Heparin-like low-affinity receptors on the surface of endothelial cells (and other cells), prepare FGFs for binding to their specific high affinity receptors; and (6) Heparin and its related polysaccharides potentiate angiostatic steroids. It is likely that future investigations will uncover even more fundamental regulatory roles for heparin as well as for other polysaccharides in the normal function of growth factors, especially in the complex process of angiogenesis.", "contents": "Control of angiogenesis by heparin and other sulfated polysaccharides. Heparin and its related polysaccharides are revealed to have important new functions as regulators of blood vessel growth and regression. This regulatory activity may be explained in part by at least five mechanisms in which heparin and heparan sulfate interact with peptide growth factors: (1) Heparin and heparan sulfate have a high affinity for angiogenic growth factors such as the fibroblast growth factors and VEGF, as well as for angiogenic inhibitors such as thrombospondin and platelet factor 4. (2) Heparin and its related polysaccharides stabilize bFGF and other growth factors. (3) FGFs and thrombospondin are stored in the extracellular matrix bound to heparan sulfate; fragments of heparin or heparan sulfate may act as natural chaperones to shuttle bFGF or other growth factors to different cellular compartments. (5) Heparin-like low-affinity receptors on the surface of endothelial cells (and other cells), prepare FGFs for binding to their specific high affinity receptors; and (6) Heparin and its related polysaccharides potentiate angiostatic steroids. It is likely that future investigations will uncover even more fundamental regulatory roles for heparin as well as for other polysaccharides in the normal function of growth factors, especially in the complex process of angiogenesis."} {"id": "PMID:1279960", "title": "Actions of nitric oxide on the acute gastrointestinal damage induced by PAF in the rat.", "content": "The actions of nitric oxide (NO) on the acute gastrointestinal damage induced by platelet-activating factor (PAF) have been investigated in the rat. S-nitroso-N-acetyl penicillamine, which spontaneously generates NO, dose-dependently inhibited PAF-induced gastrointestinal plasma leakage, a measure of the initiation of vascular damage. The inhibitor of NO synthase, NG-monomethyl-L-arginine substantially potentiated gastrointestinal damage and plasma leakage induced by E. coli endotoxin, but had no effect on that induced by intravenous infusion of PAF. Endogenous NO may thus have a protective role in the gastrointestinal vascular that can be mimicked by generators of NO. The protection afforded by endogenous NO may, however, be dependent on the nature of the inflammatory stimulus used to induce gastrointestinal damage.", "contents": "Actions of nitric oxide on the acute gastrointestinal damage induced by PAF in the rat. The actions of nitric oxide (NO) on the acute gastrointestinal damage induced by platelet-activating factor (PAF) have been investigated in the rat. S-nitroso-N-acetyl penicillamine, which spontaneously generates NO, dose-dependently inhibited PAF-induced gastrointestinal plasma leakage, a measure of the initiation of vascular damage. The inhibitor of NO synthase, NG-monomethyl-L-arginine substantially potentiated gastrointestinal damage and plasma leakage induced by E. coli endotoxin, but had no effect on that induced by intravenous infusion of PAF. Endogenous NO may thus have a protective role in the gastrointestinal vascular that can be mimicked by generators of NO. The protection afforded by endogenous NO may, however, be dependent on the nature of the inflammatory stimulus used to induce gastrointestinal damage."} {"id": "PMID:1279961", "title": "Distribution of repetitive and non-repetitive circumsporozoite protein epitopes on Plasmodium falciparum sporozoites and immunochemical characterization of human malaria antisera.", "content": "The presence and distribution of circumsporozoite protein (CSP) epitopes located in the repetitive and non-repetitive regions were studied in three Plasmodium falciparum strains, NF54, IFA5 and IFA6. It was found by immunofluorescence, Western blotting and immunoelectron microscopy that mAbs to epitopes of the repetitive domaine bound similarly to the CSP of all three strains. MAbs to epitopes of the flanking regions yielded either some strain differences (mAbs to the C-terminal end), or reacted only in immunofluorescence tests on whole sporozoites (mAbs to the N-terminal end). Human sera from an area endemic for malaria, two of them positive in ELISA on (NANP)40 and two negative, were tested for their reactivity with epitopes of the flanking regions of the CSP. The presence of antibodies to such epitopes could be demonstrated by Western blots and immunocytochemistry independent of the reactivity of the sera to recognize (NANP)40. All tested bound to salivary gland tissues but not to their secretory product in immunocytochemical experiments.", "contents": "Distribution of repetitive and non-repetitive circumsporozoite protein epitopes on Plasmodium falciparum sporozoites and immunochemical characterization of human malaria antisera. The presence and distribution of circumsporozoite protein (CSP) epitopes located in the repetitive and non-repetitive regions were studied in three Plasmodium falciparum strains, NF54, IFA5 and IFA6. It was found by immunofluorescence, Western blotting and immunoelectron microscopy that mAbs to epitopes of the repetitive domaine bound similarly to the CSP of all three strains. MAbs to epitopes of the flanking regions yielded either some strain differences (mAbs to the C-terminal end), or reacted only in immunofluorescence tests on whole sporozoites (mAbs to the N-terminal end). Human sera from an area endemic for malaria, two of them positive in ELISA on (NANP)40 and two negative, were tested for their reactivity with epitopes of the flanking regions of the CSP. The presence of antibodies to such epitopes could be demonstrated by Western blots and immunocytochemistry independent of the reactivity of the sera to recognize (NANP)40. All tested bound to salivary gland tissues but not to their secretory product in immunocytochemical experiments."} {"id": "PMID:1279962", "title": "Analysis of internal proteins of influenza A (H2N2) viruses isolated from birds in East Germany in 1983.", "content": "Proteins and RNAs of influenza A (H2N2) viruses isolated from birds in 1983 in East Germany were compared antigenically with those of H2N2 human strains. The electrophoretic mobility of the viral proteins and of the S1-treated double-stranded RNAs from two human and six avian strains, as well as the results of EIA-tests using monoclonal antibodies to their matrix protein and nucleoproteins indicate an antigenic relationship between the avian isolates and human strains of H2N2 subtype. One of the avian strains had a reduced amount of matrix protein.", "contents": "Analysis of internal proteins of influenza A (H2N2) viruses isolated from birds in East Germany in 1983. Proteins and RNAs of influenza A (H2N2) viruses isolated from birds in 1983 in East Germany were compared antigenically with those of H2N2 human strains. The electrophoretic mobility of the viral proteins and of the S1-treated double-stranded RNAs from two human and six avian strains, as well as the results of EIA-tests using monoclonal antibodies to their matrix protein and nucleoproteins indicate an antigenic relationship between the avian isolates and human strains of H2N2 subtype. One of the avian strains had a reduced amount of matrix protein."} {"id": "PMID:1279963", "title": "Effect of natural and synthetic immunomodulators on the synthesis of interferon by peritoneal cells of mice.", "content": "The effect of different natural and synthetic immunomodulators on the spontaneous interferon (IFN) synthesis by freshly isolated resident peritoneal cells of BALB/c, NZB and C3H mice was investigated. Actinomycetal glycolipids isolated from Curtobacterium betae, Faenia rectivirgula, Rothia dentocariosa and Saccharopolyspora hirsuta at the concentration 1-20 micrograms/ml were found to potentiate the IFN synthesis by the peritoneal cells of BALB/c mice. Similar results were obtained when dsRNA, LPS of Shigella sonnei and lipid A isolated from the LPS were used. The effect of potentiation of the physiological IFN production by the immunomodulators was observed also in the cells of C3H and NZB mice. In contrast, the inhibition of the IFN synthesis was observed when the peritoneal cells of BALB/c and NZB mice were treated with imuthiol at concentration 0.1-10 micrograms/ml. Thymomodulin (TFX-Polfa) at concentration of 1-100 micrograms/ml had no effect on the spontaneous IFN production.", "contents": "Effect of natural and synthetic immunomodulators on the synthesis of interferon by peritoneal cells of mice. The effect of different natural and synthetic immunomodulators on the spontaneous interferon (IFN) synthesis by freshly isolated resident peritoneal cells of BALB/c, NZB and C3H mice was investigated. Actinomycetal glycolipids isolated from Curtobacterium betae, Faenia rectivirgula, Rothia dentocariosa and Saccharopolyspora hirsuta at the concentration 1-20 micrograms/ml were found to potentiate the IFN synthesis by the peritoneal cells of BALB/c mice. Similar results were obtained when dsRNA, LPS of Shigella sonnei and lipid A isolated from the LPS were used. The effect of potentiation of the physiological IFN production by the immunomodulators was observed also in the cells of C3H and NZB mice. In contrast, the inhibition of the IFN synthesis was observed when the peritoneal cells of BALB/c and NZB mice were treated with imuthiol at concentration 0.1-10 micrograms/ml. Thymomodulin (TFX-Polfa) at concentration of 1-100 micrograms/ml had no effect on the spontaneous IFN production."} {"id": "PMID:1279964", "title": "Recombinant interferon-alpha 2 inhibits HIV replication in chronically infected promonocytic cells.", "content": "Promonocytic cells U937 with previously established HIV-1 persistent infection, were treated with increasing doses of the recombinant INF-alpha 2. This resulted in a significant decrease of virion-associated reverse transcriptase levels in medium of the cultures studied, most pronounced by the highest interferon doses, but depending on this cytokine presence. In spite of the marked restrictive effect of the interferon on the infectious virus production the synthesis, of viral structural proteins by the U937 cells, as detected by immunofluorescence, was not affected. The therapeutic index of interferon was considerably high.", "contents": "Recombinant interferon-alpha 2 inhibits HIV replication in chronically infected promonocytic cells. Promonocytic cells U937 with previously established HIV-1 persistent infection, were treated with increasing doses of the recombinant INF-alpha 2. This resulted in a significant decrease of virion-associated reverse transcriptase levels in medium of the cultures studied, most pronounced by the highest interferon doses, but depending on this cytokine presence. In spite of the marked restrictive effect of the interferon on the infectious virus production the synthesis, of viral structural proteins by the U937 cells, as detected by immunofluorescence, was not affected. The therapeutic index of interferon was considerably high."} {"id": "PMID:1279965", "title": "Finasteride for benign prostatic hyperplasia.", "content": "The pathogenesis of benign prostatic hyperplasia is related to the action of 5 alpha-dihydrotestosterone (DHT), the physiologically active form of testosterone. The conversion of testosterone to DHT is catalyzed intracellularly in prostatic tissue by the enzyme 5 alpha-reductase. Finasteride blocks the action of 5 alpha-reductase by competitively inhibiting the binding of testosterone to 5 alpha-reductase. The maximum effect of finasteride on reducing prostatic volume occurs after three months of oral therapy. Most patients experience improvement in urine flow rates, and side effects are minimal. However, following discontinuation of treatment, serum DHT levels return to baseline within two weeks.", "contents": "Finasteride for benign prostatic hyperplasia. The pathogenesis of benign prostatic hyperplasia is related to the action of 5 alpha-dihydrotestosterone (DHT), the physiologically active form of testosterone. The conversion of testosterone to DHT is catalyzed intracellularly in prostatic tissue by the enzyme 5 alpha-reductase. Finasteride blocks the action of 5 alpha-reductase by competitively inhibiting the binding of testosterone to 5 alpha-reductase. The maximum effect of finasteride on reducing prostatic volume occurs after three months of oral therapy. Most patients experience improvement in urine flow rates, and side effects are minimal. However, following discontinuation of treatment, serum DHT levels return to baseline within two weeks."} {"id": "PMID:1279966", "title": "The prevalence and prognostic significance of arrhythmias in Duchenne type muscular dystrophy.", "content": "To investigate the prevalence and prognostic significance of cardiac arrhythmias in Duchenne type muscular dystrophy 24-hour ambulatory ECG was performed in 80 patients with Duchenne type muscular dystrophy, and they were followed up for 5 years. Various arrhythmias were observed in 63.8% (51 of 80) of the patients. Ventricular premature beats were found in 30% (24 of 80), and the incidence of ventricular premature beats increased as the clinical severity of skeletal muscle involvement advanced. Forty-seven patients survived for 5 years, but the incidence of arrhythmias increased from 38.3% (18 of 47) to 74.5% (35 of 47) (p < 0.001). During the 5-year period, four of 33 deaths were sudden. Malignant ventricular premature beats (ventricular couplets, ventricular tachycardia, and R-on-T-type ventricular premature beats) were observed in three of these four patients. It appears that cardiac arrhythmias are a common complication of Duchenne type muscular dystrophy and that the incidence of ventricular arrhythmias increases with the progression of myocardial involvement. There is an association between ventricular arrhythmias and sudden death, but the reduction of ventricular arrhythmias may not reduce the incidence of episodes of sudden death.", "contents": "The prevalence and prognostic significance of arrhythmias in Duchenne type muscular dystrophy. To investigate the prevalence and prognostic significance of cardiac arrhythmias in Duchenne type muscular dystrophy 24-hour ambulatory ECG was performed in 80 patients with Duchenne type muscular dystrophy, and they were followed up for 5 years. Various arrhythmias were observed in 63.8% (51 of 80) of the patients. Ventricular premature beats were found in 30% (24 of 80), and the incidence of ventricular premature beats increased as the clinical severity of skeletal muscle involvement advanced. Forty-seven patients survived for 5 years, but the incidence of arrhythmias increased from 38.3% (18 of 47) to 74.5% (35 of 47) (p < 0.001). During the 5-year period, four of 33 deaths were sudden. Malignant ventricular premature beats (ventricular couplets, ventricular tachycardia, and R-on-T-type ventricular premature beats) were observed in three of these four patients. It appears that cardiac arrhythmias are a common complication of Duchenne type muscular dystrophy and that the incidence of ventricular arrhythmias increases with the progression of myocardial involvement. There is an association between ventricular arrhythmias and sudden death, but the reduction of ventricular arrhythmias may not reduce the incidence of episodes of sudden death."} {"id": "PMID:1279967", "title": "A multicenter, randomized, controlled trial to evaluate the effect of prophylactic octreotide on ERCP-induced pancreatitis.", "content": "Eight-four patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) were randomized to receive 100 micrograms of octreotide intravenously immediately prior to ERCP, and 100 micrograms subcutaneously 45 min after the initial dose, or placebo. Amylase, lipase, and glucose were measured and clinical assessment was performed before, and 2 and 24 h after, ERCP. We define clinical pancreatitis as the combination of elevated amylase or lipase with abdominal pain and tenderness. Interim analysis in 84 patients revealed an 11% incidence of clinical pancreatitis in the control group and 35% in the treatment group (p < 0.01). There were no differences in either group with respect to sphincterotomy, gender, age, duration of ERCP, number of cannulations of the pancreatic duct, degree of duct injection, or the volume of contrast injected. Analysis of group differences stratified by sphincterotomy revealed the following: 1) In patients who did not undergo a sphincterotomy, there was a significantly higher rate of pancreatitis in the treatment group [10/17 (59%) versus 1/17 (6%) RR 10.0 (95% CI 1.4-69.8)]. 2) Sphincterotomy reduced the rate of pancreatitis in patients who received octreotide from 10/17 (59% no sphincterotomy), to 3/20 (15% sphincterotomy) (p = 0.01), which equals the rate in patients who received placebo and underwent sphincterotomy [4/25 (16%)]. 3) Although the incidence of pancreatitis was higher in the treatment group, octreotide may reduce the severity of pancreatitis measured by the number of days NPO (Wilcoxon rank sum, p = 0.02), length of stay after ERCP (p = 0.13), the number of days of pain (p = 0.11), and the degree of amylase elevation (p = 0.04). We conclude that: 1) Octreotide appears to increase the incidence of pancreatitis when given prophylactically for diagnostic ERCP. 2) Although pancreatitis was more common in the octreotide group, it was less severe than the placebo group. 3) Sphincterotomy may afford protection against pancreatitis in patients who received octreotide. 4) We cannot recommend the use of prophylactic octreotide during diagnostic or therapeutic ERCP.", "contents": "A multicenter, randomized, controlled trial to evaluate the effect of prophylactic octreotide on ERCP-induced pancreatitis. Eight-four patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) were randomized to receive 100 micrograms of octreotide intravenously immediately prior to ERCP, and 100 micrograms subcutaneously 45 min after the initial dose, or placebo. Amylase, lipase, and glucose were measured and clinical assessment was performed before, and 2 and 24 h after, ERCP. We define clinical pancreatitis as the combination of elevated amylase or lipase with abdominal pain and tenderness. Interim analysis in 84 patients revealed an 11% incidence of clinical pancreatitis in the control group and 35% in the treatment group (p < 0.01). There were no differences in either group with respect to sphincterotomy, gender, age, duration of ERCP, number of cannulations of the pancreatic duct, degree of duct injection, or the volume of contrast injected. Analysis of group differences stratified by sphincterotomy revealed the following: 1) In patients who did not undergo a sphincterotomy, there was a significantly higher rate of pancreatitis in the treatment group [10/17 (59%) versus 1/17 (6%) RR 10.0 (95% CI 1.4-69.8)]. 2) Sphincterotomy reduced the rate of pancreatitis in patients who received octreotide from 10/17 (59% no sphincterotomy), to 3/20 (15% sphincterotomy) (p = 0.01), which equals the rate in patients who received placebo and underwent sphincterotomy [4/25 (16%)]. 3) Although the incidence of pancreatitis was higher in the treatment group, octreotide may reduce the severity of pancreatitis measured by the number of days NPO (Wilcoxon rank sum, p = 0.02), length of stay after ERCP (p = 0.13), the number of days of pain (p = 0.11), and the degree of amylase elevation (p = 0.04). We conclude that: 1) Octreotide appears to increase the incidence of pancreatitis when given prophylactically for diagnostic ERCP. 2) Although pancreatitis was more common in the octreotide group, it was less severe than the placebo group. 3) Sphincterotomy may afford protection against pancreatitis in patients who received octreotide. 4) We cannot recommend the use of prophylactic octreotide during diagnostic or therapeutic ERCP."} {"id": "PMID:1279968", "title": "Chronic and intradialytic effects of high-flux hemodialysis on tumor necrosis factor-alpha production: relationship to endotoxins.", "content": "Tumor necrosis factor-alpha (TNF alpha) likely plays a role in hemodialysis-associated complications. As TNF alpha is mainly produced by monocytes in response to endotoxins, we studied its production and the presence of circulating endotoxins in patients dialyzed on polyacrylonitrile (PAN) membrane. Spontaneous production of TNF alpha was observed in patients before the dialysis session and increased during the session. Endotoxins were present in serum from patients chronically dialyzed with PAN and increased during hemodialysis session. In addition, intradialytic decrease in CD14 antigen expression on circulating monocytes, which could be caused by endotoxins, was found. The continuous presence of low amounts of circulating endotoxins between sessions may explain the chronic increase in TNF alpha secretion, while high amounts of circulating endotoxins may account for intradialytic oversecretion of TNF alpha and downmodulation of CD14. We suggest that endotoxin-free dialysates should be a prerequisite for the use of high-flux membranes.", "contents": "Chronic and intradialytic effects of high-flux hemodialysis on tumor necrosis factor-alpha production: relationship to endotoxins. Tumor necrosis factor-alpha (TNF alpha) likely plays a role in hemodialysis-associated complications. As TNF alpha is mainly produced by monocytes in response to endotoxins, we studied its production and the presence of circulating endotoxins in patients dialyzed on polyacrylonitrile (PAN) membrane. Spontaneous production of TNF alpha was observed in patients before the dialysis session and increased during the session. Endotoxins were present in serum from patients chronically dialyzed with PAN and increased during hemodialysis session. In addition, intradialytic decrease in CD14 antigen expression on circulating monocytes, which could be caused by endotoxins, was found. The continuous presence of low amounts of circulating endotoxins between sessions may explain the chronic increase in TNF alpha secretion, while high amounts of circulating endotoxins may account for intradialytic oversecretion of TNF alpha and downmodulation of CD14. We suggest that endotoxin-free dialysates should be a prerequisite for the use of high-flux membranes."} {"id": "PMID:1279969", "title": "Nonmucinous nature of the surface material of the bladder mucosa.", "content": "The urinary bladder is lined by transitional epithelium, also known as urothelium. Some investigators have described a material known as mucin, which lines the luminal surface of the urothelium, but its nature is not well understood. The authors examined sections of bladder from rat, mouse, rabbit, and man and found that, although they reacted differently to common histochemical stains for complex carbohydrates, none showed any material that stained as mucin on the surface of the mucosa. Rather, intracellular granules that have varying staining characteristics in different animals were found on the luminal side of the urothelium. The authors speculate, based on their histochemical findings, that some form of mucin may be present in the urothelial granules in man and that studies on animals may not be applicable to man.", "contents": "Nonmucinous nature of the surface material of the bladder mucosa. The urinary bladder is lined by transitional epithelium, also known as urothelium. Some investigators have described a material known as mucin, which lines the luminal surface of the urothelium, but its nature is not well understood. The authors examined sections of bladder from rat, mouse, rabbit, and man and found that, although they reacted differently to common histochemical stains for complex carbohydrates, none showed any material that stained as mucin on the surface of the mucosa. Rather, intracellular granules that have varying staining characteristics in different animals were found on the luminal side of the urothelium. The authors speculate, based on their histochemical findings, that some form of mucin may be present in the urothelial granules in man and that studies on animals may not be applicable to man."} {"id": "PMID:1279970", "title": "Elevated second trimester maternal serum beta-HCG concentrations and subsequent adverse pregnancy outcome.", "content": "Previous studies have found an association between elevated second trimester maternal serum alpha-fetoprotein (MS-AFP), in the absence of fetal anomalies, and adverse pregnancy outcome. We studied the association between elevated second trimester maternal serum beta-HCG, now also routinely measured by prenatal screening programs, and adverse pregnancy outcome by reviewing retrospectively the pregnancy outcomes among women with markedly elevated midtrimester beta-HCG in our prenatal screening program. Seven (0.23%) of 3,000 consecutively screened women had a serum beta-HCG above 5 MOM. Four (57%) of these 7 women had an adverse pregnancy outcome including severe preeclampsia (n = 2), abruptio placentae (n = 1), or preterm labor (n = 1). A concurrently elevated MS-AFP was found in only one of these 4 patients. Elevated mid-trimester maternal serum beta-HCG may be an independent risk factor for subsequent adverse pregnancy outcomes.", "contents": "Elevated second trimester maternal serum beta-HCG concentrations and subsequent adverse pregnancy outcome. Previous studies have found an association between elevated second trimester maternal serum alpha-fetoprotein (MS-AFP), in the absence of fetal anomalies, and adverse pregnancy outcome. We studied the association between elevated second trimester maternal serum beta-HCG, now also routinely measured by prenatal screening programs, and adverse pregnancy outcome by reviewing retrospectively the pregnancy outcomes among women with markedly elevated midtrimester beta-HCG in our prenatal screening program. Seven (0.23%) of 3,000 consecutively screened women had a serum beta-HCG above 5 MOM. Four (57%) of these 7 women had an adverse pregnancy outcome including severe preeclampsia (n = 2), abruptio placentae (n = 1), or preterm labor (n = 1). A concurrently elevated MS-AFP was found in only one of these 4 patients. Elevated mid-trimester maternal serum beta-HCG may be an independent risk factor for subsequent adverse pregnancy outcomes."} {"id": "PMID:1279971", "title": "Deletion of the KIT and PDGFRA genes in a patient with piebaldism.", "content": "We have previously shown that human piebaldism results from mutations of the KIT gene, which encodes the receptor for the mast/stem cell growth factor and is located in chromosome segment 4q12. Using DNA of a patient with piebaldism, mental retardation, and multiple congenital anomalies associated with a 46,XY,del(4) (q12q21.1) karyotype, we carried out quantitative Southern blot hybridization analyses of the KIT gene and the adjacent PDGFRA (platelet-derived growth factor receptor alpha subunit) genes. The patient was hemizygous for both the KIT and PDGFRA genes, indicating that both of these genes are included within the deleted region. Therefore, deletion of the KIT and PDGFRA genes may account for the piebald phenotype in this patient.", "contents": "Deletion of the KIT and PDGFRA genes in a patient with piebaldism. We have previously shown that human piebaldism results from mutations of the KIT gene, which encodes the receptor for the mast/stem cell growth factor and is located in chromosome segment 4q12. Using DNA of a patient with piebaldism, mental retardation, and multiple congenital anomalies associated with a 46,XY,del(4) (q12q21.1) karyotype, we carried out quantitative Southern blot hybridization analyses of the KIT gene and the adjacent PDGFRA (platelet-derived growth factor receptor alpha subunit) genes. The patient was hemizygous for both the KIT and PDGFRA genes, indicating that both of these genes are included within the deleted region. Therefore, deletion of the KIT and PDGFRA genes may account for the piebald phenotype in this patient."} {"id": "PMID:1279972", "title": "Cyclooxygenase products do not modulate angiotensin II-induced contractions of human chorionic plate arteries.", "content": "This study sought to determine whether cyclooxygenase products modulate angiotensin II-induced contractions of human placental arteries. Ring segments of chorionic plate arteries (3 to 5 mm inner diameter) were obtained after normal vaginal deliveries. Active force in response to 10(-6) mol/L angiotensin II or 10(-4) mol/L arachidonic acid was measured in the presence or absence of 10(-6) mol/L indomethacin to inhibit cyclooxygenase. The response of K+ contracted arteries to the stable prostacyclin analog iloprost was also tested to determine whether prostacyclin relaxes these vessels. Statistical differences were assessed by analysis of variance, Wilcoxon sign rank test, or Student t test with Bonferroni correction for multiple comparisons. Successive applications of angiotensin II produced significantly less contraction than the original dose (angiotensin II tachyphylaxis). Angiotensin II tachyphylaxis was unaffected by indomethacin. Arachidonic acid caused an indomethacin-sensitive contraction and iloprost failed to relax the arteries. These results suggest that cyclooxygenase products do not mediate angiotensin II tachyphylaxis in these vessels.", "contents": "Cyclooxygenase products do not modulate angiotensin II-induced contractions of human chorionic plate arteries. This study sought to determine whether cyclooxygenase products modulate angiotensin II-induced contractions of human placental arteries. Ring segments of chorionic plate arteries (3 to 5 mm inner diameter) were obtained after normal vaginal deliveries. Active force in response to 10(-6) mol/L angiotensin II or 10(-4) mol/L arachidonic acid was measured in the presence or absence of 10(-6) mol/L indomethacin to inhibit cyclooxygenase. The response of K+ contracted arteries to the stable prostacyclin analog iloprost was also tested to determine whether prostacyclin relaxes these vessels. Statistical differences were assessed by analysis of variance, Wilcoxon sign rank test, or Student t test with Bonferroni correction for multiple comparisons. Successive applications of angiotensin II produced significantly less contraction than the original dose (angiotensin II tachyphylaxis). Angiotensin II tachyphylaxis was unaffected by indomethacin. Arachidonic acid caused an indomethacin-sensitive contraction and iloprost failed to relax the arteries. These results suggest that cyclooxygenase products do not mediate angiotensin II tachyphylaxis in these vessels."} {"id": "PMID:1279973", "title": "Simplified gram stain interpretive method for diagnosis of bacterial vaginosis.", "content": "Two methods which only consider bacterial morphotypes and require counting various types of bacteria, for interpreting Gram stains of vaginal secretions for the purpose of diagnosing bacterial vaginosis were previously described. A new interpretative method, which combines clue cells with bacterial morphotypes as diagnostic markers, is offered. One hundred twenty patients were tested with the new interpretative method and clinical criteria of bacterial vaginosis as the reference standard. The new method was found comparable to older methods when all were compared with clinical diagnostic methods. The sensitivity of the clue cell method was 86.1% and the specificity was 92.8%. The predictive value of a positive test was 83.7% for a population with a prevalence of bacterial vaginosis of 30%. The negative predictive value was 94.0%. If clue cells are present and the nonlactobacilli morphotypes exceed lactobacilli morphotypes, bacterial vaginosis can be diagnosed without the need for exact bacterial counts.", "contents": "Simplified gram stain interpretive method for diagnosis of bacterial vaginosis. Two methods which only consider bacterial morphotypes and require counting various types of bacteria, for interpreting Gram stains of vaginal secretions for the purpose of diagnosing bacterial vaginosis were previously described. A new interpretative method, which combines clue cells with bacterial morphotypes as diagnostic markers, is offered. One hundred twenty patients were tested with the new interpretative method and clinical criteria of bacterial vaginosis as the reference standard. The new method was found comparable to older methods when all were compared with clinical diagnostic methods. The sensitivity of the clue cell method was 86.1% and the specificity was 92.8%. The predictive value of a positive test was 83.7% for a population with a prevalence of bacterial vaginosis of 30%. The negative predictive value was 94.0%. If clue cells are present and the nonlactobacilli morphotypes exceed lactobacilli morphotypes, bacterial vaginosis can be diagnosed without the need for exact bacterial counts."} {"id": "PMID:1279974", "title": "Inhibitory effect of medroxyprogesterone acetate on angiogenesis induced by human endometrial cancer.", "content": "The purpose of this study was to investigate the effect of medroxyprogesterone acetate on angiogenesis induced by endometrial cancer and to elucidate the possible mechanisms by which it inhibits the growth of the cancer. Tumors were obtained from 29 patients with endometrial adenocarcinoma, and angiogenesis was assayed in corneas of white rabbits. Transplantation of tumor tissues into rabbit corneas induced angiogenesis in 70.4% of the corneas, but their transplantation with a pellet of medroxyprogesterone acetate induced angiogenesis in only 21.5% of the corneas. This compound also inhibited angiogenesis induced by acidic fibroblast growth factor and transforming growth factor-alpha. Inhibition of angiogenesis may be one mechanism by which medroxyprogesterone acetate inhibits the growth of endometrial adenocarcinoma, and its inhibition of neovascularization induced by adenocarcinoma may be through its direct action on endothelial cells.", "contents": "Inhibitory effect of medroxyprogesterone acetate on angiogenesis induced by human endometrial cancer. The purpose of this study was to investigate the effect of medroxyprogesterone acetate on angiogenesis induced by endometrial cancer and to elucidate the possible mechanisms by which it inhibits the growth of the cancer. Tumors were obtained from 29 patients with endometrial adenocarcinoma, and angiogenesis was assayed in corneas of white rabbits. Transplantation of tumor tissues into rabbit corneas induced angiogenesis in 70.4% of the corneas, but their transplantation with a pellet of medroxyprogesterone acetate induced angiogenesis in only 21.5% of the corneas. This compound also inhibited angiogenesis induced by acidic fibroblast growth factor and transforming growth factor-alpha. Inhibition of angiogenesis may be one mechanism by which medroxyprogesterone acetate inhibits the growth of endometrial adenocarcinoma, and its inhibition of neovascularization induced by adenocarcinoma may be through its direct action on endothelial cells."} {"id": "PMID:1279975", "title": "Evaluation of rapid diagnostic tests in the detection of microbial invasion of the amniotic cavity.", "content": "We sought to determine and compare the value of several rapid diagnostic tests in the detection of intraamniotic infection. Gram stain, intraamniotic glucose level determination, leukocyte esterase assay, and the Limulus amebocyte lysate assay were performed on 144 amniotic fluid specimens retrieved by transabdominal amniocentesis in 136 patients with preterm premature rupture of the membranes or preterm labor. Diagnostic indices for a positive amniotic fluid culture and the development of clinical infection were calculated for each rapid test. Receiver-operator characteristic curves were generated to help select the optimal glucose level and combination of tests to detect intraamniotic infection. The greatest sensitivity for predicting either a positive culture or subsequent clinical infection in preterm labor patients and in predicting clinical infection in patients with preterm premature rupture of the membranes was demonstrated by a low glucose level. The Gram stain provided the greatest positive predictive value in patients with preterm labor. Combining the Gram stain and measurement of intraamniotic glucose levels did not improve sensitivity above glucose alone or positive predictive value above Gram stain alone. Leukocyte esterase determination and Limulus amebocyte lysate assay are insensitive indicators of intraamniotic infection. Selection of Gram stain or glucose level measurement alone or in combination as an appropriate screen for intraamniotic infection will depend on the clinicians' false-positive rate threshold.", "contents": "Evaluation of rapid diagnostic tests in the detection of microbial invasion of the amniotic cavity. We sought to determine and compare the value of several rapid diagnostic tests in the detection of intraamniotic infection. Gram stain, intraamniotic glucose level determination, leukocyte esterase assay, and the Limulus amebocyte lysate assay were performed on 144 amniotic fluid specimens retrieved by transabdominal amniocentesis in 136 patients with preterm premature rupture of the membranes or preterm labor. Diagnostic indices for a positive amniotic fluid culture and the development of clinical infection were calculated for each rapid test. Receiver-operator characteristic curves were generated to help select the optimal glucose level and combination of tests to detect intraamniotic infection. The greatest sensitivity for predicting either a positive culture or subsequent clinical infection in preterm labor patients and in predicting clinical infection in patients with preterm premature rupture of the membranes was demonstrated by a low glucose level. The Gram stain provided the greatest positive predictive value in patients with preterm labor. Combining the Gram stain and measurement of intraamniotic glucose levels did not improve sensitivity above glucose alone or positive predictive value above Gram stain alone. Leukocyte esterase determination and Limulus amebocyte lysate assay are insensitive indicators of intraamniotic infection. Selection of Gram stain or glucose level measurement alone or in combination as an appropriate screen for intraamniotic infection will depend on the clinicians' false-positive rate threshold."} {"id": "PMID:1279976", "title": "Congenital nephrosis: detection of index cases through maternal serum alpha-fetoprotein screening.", "content": "Congenital nephrosis is an autosomal recessive disorder with an incidence of 1 in 8000 in Finland, but it is quite rare in non-Finnish populations. In families known to be at risk, prenatal detection is possible by means of maternal serum and/or amniotic fluid alpha-fetoprotein levels. We report the antenatal diagnosis of four cases of congenital nephrosis, three of which were index cases, through maternal serum alpha-fetoprotein screening. The diagnosis was confirmed at birth in two infants. Two patients elected to terminate their pregnancies, and the diagnoses were confirmed pathologically (obliteration of foot processes on electron microscopy of fetal glomeruli) in both. In cases of elevated maternal serum alpha-fetoprotein, with unexplained and marked elevations of amniotic fluid alpha-fetoprotein and normal acetylcholinesterase levels, the diagnosis of congenital nephrosis must be considered regardless of ethnic origin.", "contents": "Congenital nephrosis: detection of index cases through maternal serum alpha-fetoprotein screening. Congenital nephrosis is an autosomal recessive disorder with an incidence of 1 in 8000 in Finland, but it is quite rare in non-Finnish populations. In families known to be at risk, prenatal detection is possible by means of maternal serum and/or amniotic fluid alpha-fetoprotein levels. We report the antenatal diagnosis of four cases of congenital nephrosis, three of which were index cases, through maternal serum alpha-fetoprotein screening. The diagnosis was confirmed at birth in two infants. Two patients elected to terminate their pregnancies, and the diagnoses were confirmed pathologically (obliteration of foot processes on electron microscopy of fetal glomeruli) in both. In cases of elevated maternal serum alpha-fetoprotein, with unexplained and marked elevations of amniotic fluid alpha-fetoprotein and normal acetylcholinesterase levels, the diagnosis of congenital nephrosis must be considered regardless of ethnic origin."} {"id": "PMID:1279978", "title": "Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus.", "content": "AIDS encephalitis is a common sequela to HIV-1 infection in humans and simian immunodeficiency virus (SIVmac) infection in macaques. Although lentiviral-infected macrophages comprise parenchymal inflammatory infiltrates in affected brain tissue, the mechanisms responsible for leukocyte trafficking to the central nervous system in AIDS are unknown. In this study, we investigated the expression of various endothelial-derived leukocyte adhesion proteins in SIVmac-induced AIDS encephalitis. Encephalitic brains from SIVmac-infected macaques, but not uninflamed brains from other SIVmac-infected animals, were found to express abundant vascular cell adhesion molecule-1 (VCAM-1) protein on the majority of arteriolar, venular, and capillary endothelial cells. Soluble VCAM-1 concentrations in cerebrospinal fluid (CSF) from encephalitic animals were increased approximately 20-fold above those from animals without AIDS encephalitis. Expression of other endothelial-related adhesion molecules, including E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1), was not uniformly associated with AIDS encephalitis. Thus, the presence of VCAM-1 in both brain and CSF was uniformly associated with SIVmac-induced disease of the central nervous system, and this expression may, at least in part, influence monocyte and lymphocyte recruitment to the central nervous system during the development of AIDS encephalitis. Moreover, measurement of soluble VCAM-1 in CSF may assist in the clinical assessment of animals or people with AIDS.", "contents": "Elevated vascular cell adhesion molecule-1 in AIDS encephalitis induced by simian immunodeficiency virus. AIDS encephalitis is a common sequela to HIV-1 infection in humans and simian immunodeficiency virus (SIVmac) infection in macaques. Although lentiviral-infected macrophages comprise parenchymal inflammatory infiltrates in affected brain tissue, the mechanisms responsible for leukocyte trafficking to the central nervous system in AIDS are unknown. In this study, we investigated the expression of various endothelial-derived leukocyte adhesion proteins in SIVmac-induced AIDS encephalitis. Encephalitic brains from SIVmac-infected macaques, but not uninflamed brains from other SIVmac-infected animals, were found to express abundant vascular cell adhesion molecule-1 (VCAM-1) protein on the majority of arteriolar, venular, and capillary endothelial cells. Soluble VCAM-1 concentrations in cerebrospinal fluid (CSF) from encephalitic animals were increased approximately 20-fold above those from animals without AIDS encephalitis. Expression of other endothelial-related adhesion molecules, including E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1), was not uniformly associated with AIDS encephalitis. Thus, the presence of VCAM-1 in both brain and CSF was uniformly associated with SIVmac-induced disease of the central nervous system, and this expression may, at least in part, influence monocyte and lymphocyte recruitment to the central nervous system during the development of AIDS encephalitis. Moreover, measurement of soluble VCAM-1 in CSF may assist in the clinical assessment of animals or people with AIDS."} {"id": "PMID:1279979", "title": "Sequential changes in histologic pattern and extracellular matrix deposition during the healing of chronic venous ulcers.", "content": "As part of a major clinical trial, sequential biopsies were taken from the margins of venous leg ulcers during their healing. The changing patterns of tissue architecture and extracellular matrix synthesis during healing were documented histologically and immunocytochemically. Initial biopsies were similar in appearance: prominent fibrin cuffs, variable inflammation, hemosiderin, and red blood cell extravasation. So called \"fibrin cuffs\" were highly organized structures composed of laminin, fibronectin, tenascin, and collagen as well as trapped leukocytes and fibrin. Fibronectin was absent from the ulcer tissue although collagen was abundant. Major histologic changes were observed after 2 weeks' pressure bandage therapy; hemosiderin, acute inflammation, and granulation tissue with the deposition of fibronectin had all increased and epithelial migration had commenced. Complete epithelialization was frequent by the fourth week of treatment, but the basement membrane was incomplete. At this time, hemosiderin and red blood cell extravasation had decreased and \"fibrin cuffs\" were virtually absent although chronic inflammation remained. The complex organization of the so-called \"fibrin cuffs\" may inhibit angiogenesis (but offer protection against increased venous pressure) in addition to their previously ascribed role in causing tissue ischemia.", "contents": "Sequential changes in histologic pattern and extracellular matrix deposition during the healing of chronic venous ulcers. As part of a major clinical trial, sequential biopsies were taken from the margins of venous leg ulcers during their healing. The changing patterns of tissue architecture and extracellular matrix synthesis during healing were documented histologically and immunocytochemically. Initial biopsies were similar in appearance: prominent fibrin cuffs, variable inflammation, hemosiderin, and red blood cell extravasation. So called \"fibrin cuffs\" were highly organized structures composed of laminin, fibronectin, tenascin, and collagen as well as trapped leukocytes and fibrin. Fibronectin was absent from the ulcer tissue although collagen was abundant. Major histologic changes were observed after 2 weeks' pressure bandage therapy; hemosiderin, acute inflammation, and granulation tissue with the deposition of fibronectin had all increased and epithelial migration had commenced. Complete epithelialization was frequent by the fourth week of treatment, but the basement membrane was incomplete. At this time, hemosiderin and red blood cell extravasation had decreased and \"fibrin cuffs\" were virtually absent although chronic inflammation remained. The complex organization of the so-called \"fibrin cuffs\" may inhibit angiogenesis (but offer protection against increased venous pressure) in addition to their previously ascribed role in causing tissue ischemia."} {"id": "PMID:1279980", "title": "Epitopes of human immunodeficiency virus regulatory proteins tat, nef, and rev are expressed in normal human tissue.", "content": "The expression of regulatory proteins tat, rev, and nef of human immunodeficiency virus type-1 (HIV-1) and tat of HIV-2 was studied in frozen sections of lymph nodes from HIV-1-infected individuals, and various tissues from uninfected persons. In HIV-1-positive lymph nodes, monoclonal antibodies to HIV-1-tat stained solitary cells in the germinal centers and interfollicular zones, and vascular endothelium. Staining by an anti-nef monoclonal antibody was restricted to follicular dendritic cells, whereas anti-rev antibody bound to fibriohistiocytes and high endothelial venules. The antibodies used labeled several cell types in tissues from uninfected individuals. Anti-HIV-1-tat antibodies labeled blood vessels and Hassall's corpuscles in skin and thymus; goblet cells in intestinal tissue and trachea; neural cells in brain and spinal cord; and zymogen-producing cells in pancreas. Anti-rev antibody stained high endothelial venules, Hassall's corpuscles and histiocytes. One anti-nef antibody solely stained follicular dendritic cells in spleen, tonsil, lymph node and Peyer's patches, whereas two other anti-nef antibodies bound to astrocytes, solitary cells in the interfollicular zones of lymph nodes, and skin cells. The current results hamper the immunohistochemical study for pathogenetic and diagnostic use of HIV regulatory protein expression in infected tissue specimens or cells.", "contents": "Epitopes of human immunodeficiency virus regulatory proteins tat, nef, and rev are expressed in normal human tissue. The expression of regulatory proteins tat, rev, and nef of human immunodeficiency virus type-1 (HIV-1) and tat of HIV-2 was studied in frozen sections of lymph nodes from HIV-1-infected individuals, and various tissues from uninfected persons. In HIV-1-positive lymph nodes, monoclonal antibodies to HIV-1-tat stained solitary cells in the germinal centers and interfollicular zones, and vascular endothelium. Staining by an anti-nef monoclonal antibody was restricted to follicular dendritic cells, whereas anti-rev antibody bound to fibriohistiocytes and high endothelial venules. The antibodies used labeled several cell types in tissues from uninfected individuals. Anti-HIV-1-tat antibodies labeled blood vessels and Hassall's corpuscles in skin and thymus; goblet cells in intestinal tissue and trachea; neural cells in brain and spinal cord; and zymogen-producing cells in pancreas. Anti-rev antibody stained high endothelial venules, Hassall's corpuscles and histiocytes. One anti-nef antibody solely stained follicular dendritic cells in spleen, tonsil, lymph node and Peyer's patches, whereas two other anti-nef antibodies bound to astrocytes, solitary cells in the interfollicular zones of lymph nodes, and skin cells. The current results hamper the immunohistochemical study for pathogenetic and diagnostic use of HIV regulatory protein expression in infected tissue specimens or cells."} {"id": "PMID:1279981", "title": "Differences in gap junction channels between cardiac myocytes, fibroblasts, and heterologous pairs.", "content": "Cultures of neonatal rat heart cells contain predominantly myocytes and fibroblastic cells. Most abundant are groups of synchronously contracting myocytes, which are electrically well coupled through large gap junctions. Cardiac fibroblasts may be electrically coupled to each other and to adjacent myocytes, be it with low intercellular conductances. Nevertheless, synchronously beating myocytes interconnected via a fibroblast were present, demonstrating that nonexcitable cardiac cells are capable of passive impulse conduction. In fibroblast pairs as well as in myocyte-fibroblast cell pairs, no sensitivity to junctional voltage could be detected when transjunctional conductance was > 1-2 nS. However, in pairs coupled by a conductance of < 1 nS, complex voltage-dependent gating was evident; gap junction channel open probability decreased with increasing junctional voltage but a nongated residual conductance remained at all voltages tested. Single gap junction channel conductance between fibroblasts was approximately 21 pS, very similar to an approximately 18-pS channel conductance that was found between myocytes next to the major conductance of 43 pS. Single-channel conductance in heterologous myocyte-fibroblast gap junctions was approximately 32 pS, which matches the theoretical value of 29 pS for gap junction channels composed of a fibroblast connexon and the major myocyte connexon. A site-directed antibody against rat heart gap junction protein connexin43 recognized gap junctions between neonatal cardiomyocytes, as demonstrated by immunocytochemical labeling. In contrast, junctions between fibroblasts showed no labeling, while in myocyte-fibroblast junctions labeling occasionally was present. Our results suggest the existence of two gap junction proteins between neonatal rat cardiocytes, connexin43 and another yet unidentified connexin. An alternative explanation (cell-specific regulation of the conductance of connexin43 channels) is discussed.", "contents": "Differences in gap junction channels between cardiac myocytes, fibroblasts, and heterologous pairs. Cultures of neonatal rat heart cells contain predominantly myocytes and fibroblastic cells. Most abundant are groups of synchronously contracting myocytes, which are electrically well coupled through large gap junctions. Cardiac fibroblasts may be electrically coupled to each other and to adjacent myocytes, be it with low intercellular conductances. Nevertheless, synchronously beating myocytes interconnected via a fibroblast were present, demonstrating that nonexcitable cardiac cells are capable of passive impulse conduction. In fibroblast pairs as well as in myocyte-fibroblast cell pairs, no sensitivity to junctional voltage could be detected when transjunctional conductance was > 1-2 nS. However, in pairs coupled by a conductance of < 1 nS, complex voltage-dependent gating was evident; gap junction channel open probability decreased with increasing junctional voltage but a nongated residual conductance remained at all voltages tested. Single gap junction channel conductance between fibroblasts was approximately 21 pS, very similar to an approximately 18-pS channel conductance that was found between myocytes next to the major conductance of 43 pS. Single-channel conductance in heterologous myocyte-fibroblast gap junctions was approximately 32 pS, which matches the theoretical value of 29 pS for gap junction channels composed of a fibroblast connexon and the major myocyte connexon. A site-directed antibody against rat heart gap junction protein connexin43 recognized gap junctions between neonatal cardiomyocytes, as demonstrated by immunocytochemical labeling. In contrast, junctions between fibroblasts showed no labeling, while in myocyte-fibroblast junctions labeling occasionally was present. Our results suggest the existence of two gap junction proteins between neonatal rat cardiocytes, connexin43 and another yet unidentified connexin. An alternative explanation (cell-specific regulation of the conductance of connexin43 channels) is discussed."} {"id": "PMID:1279982", "title": "Neurokinin3 receptor regulation of acetylcholine release from myenteric plexus.", "content": "This study sought to characterize the action of neurokinin B (NKB) and senktide, a selective synthetic agonist for NK3 receptors, on the myenteric plexus of the guinea pig small intestine. Both peptides stimulated a dose-dependent release of [3H]-acetylcholine (ACh). The mean effective dose values were 1 x 10(-9) for NKB and 3 x 10(-11) M for senktide. The action of these two neurokinins was blocked by the removal of Ca2+ and was sensitive to tetrodotoxin. The release of [3H]ACh was antagonized by omega-conotoxin GVIA, implying the involvement of N-type voltage-sensitive calcium channels. Senktide-evoked ACh release was also insensitive to nifedipine or flunarizine but was blocked by diltiazem. Treatment with protein kinase C (PKC) inhibitors (H-7 and polymyxin B) or activators (12-tetradecanoylphorbol 13-acetate and SC-9) failed to alter the NK3 receptor-mediated ACh output. Our data did not support an action mediated via PKC upon the activation of NK3 receptors on myenteric cholinergic neurons.", "contents": "Neurokinin3 receptor regulation of acetylcholine release from myenteric plexus. This study sought to characterize the action of neurokinin B (NKB) and senktide, a selective synthetic agonist for NK3 receptors, on the myenteric plexus of the guinea pig small intestine. Both peptides stimulated a dose-dependent release of [3H]-acetylcholine (ACh). The mean effective dose values were 1 x 10(-9) for NKB and 3 x 10(-11) M for senktide. The action of these two neurokinins was blocked by the removal of Ca2+ and was sensitive to tetrodotoxin. The release of [3H]ACh was antagonized by omega-conotoxin GVIA, implying the involvement of N-type voltage-sensitive calcium channels. Senktide-evoked ACh release was also insensitive to nifedipine or flunarizine but was blocked by diltiazem. Treatment with protein kinase C (PKC) inhibitors (H-7 and polymyxin B) or activators (12-tetradecanoylphorbol 13-acetate and SC-9) failed to alter the NK3 receptor-mediated ACh output. Our data did not support an action mediated via PKC upon the activation of NK3 receptors on myenteric cholinergic neurons."} {"id": "PMID:1279983", "title": "Neuropeptides promote neutrophil adherence to endothelial cell monolayers.", "content": "The objective of this study was to determine whether substance P and calcitonin gene-related peptide (CGRP), at physiologically relevant concentrations, affect leukocyte-endothelial cell adhesion. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated (40 min) with freshly isolated human neutrophils in the presence or absence of substance P or CGRP (10(-11) M). Both substance P and CGRP caused a significant increase (2-fold) in neutrophil adherence to HUVEC. Monoclonal antibodies (MAb) directed against the leukocyte adhesion glycoproteins CD11/CD18 (MAb IB4) and L-selectin (MAb DREG56) did not attenuate substance P-induced adhesion. Antibodies directed against the endothelial cell adhesion molecules E-selectin (MAb CL2) and ICAM-1 (MAb R6.5) were also without effect on substance P-induced neutrophil adhesion. Similar results were obtained when either MAb IB4, DREG56, CL2, or R6.5 was coincubated with CGRP-stimulated neutrophils and endothelial cells. Phorbol 12-myristate 13-acetate-stimulated neutrophil adherence was significantly attenuated by MAb IB4, indicating that CD11/CD18 participates in this adhesion process. The results of this study indicate that 1) the neuropeptides substance P and CGRP promote neutrophil adherence to venular endothelium and 2) the neuropeptide-induced adhesion is not mediated by the adhesion molecules CD11/CD18, L-selectin, E-selectin, or ICAM-1.", "contents": "Neuropeptides promote neutrophil adherence to endothelial cell monolayers. The objective of this study was to determine whether substance P and calcitonin gene-related peptide (CGRP), at physiologically relevant concentrations, affect leukocyte-endothelial cell adhesion. Confluent monolayers of human umbilical vein endothelial cells (HUVEC) were incubated (40 min) with freshly isolated human neutrophils in the presence or absence of substance P or CGRP (10(-11) M). Both substance P and CGRP caused a significant increase (2-fold) in neutrophil adherence to HUVEC. Monoclonal antibodies (MAb) directed against the leukocyte adhesion glycoproteins CD11/CD18 (MAb IB4) and L-selectin (MAb DREG56) did not attenuate substance P-induced adhesion. Antibodies directed against the endothelial cell adhesion molecules E-selectin (MAb CL2) and ICAM-1 (MAb R6.5) were also without effect on substance P-induced neutrophil adhesion. Similar results were obtained when either MAb IB4, DREG56, CL2, or R6.5 was coincubated with CGRP-stimulated neutrophils and endothelial cells. Phorbol 12-myristate 13-acetate-stimulated neutrophil adherence was significantly attenuated by MAb IB4, indicating that CD11/CD18 participates in this adhesion process. The results of this study indicate that 1) the neuropeptides substance P and CGRP promote neutrophil adherence to venular endothelium and 2) the neuropeptide-induced adhesion is not mediated by the adhesion molecules CD11/CD18, L-selectin, E-selectin, or ICAM-1."} {"id": "PMID:1279984", "title": "Mechanisms of neurotensin-induced inhibition in rat ileal smooth muscle.", "content": "The aim of the present study was to determine the mechanisms of neurotensin-induced inhibition in ileal smooth muscle. Isolated rat ileal smooth muscle strips were stimulated in an organ bath using carbachol (CCH) or by KCl depolarization. Neurotensin produced a concentration-dependent inhibition of muscle contraction [mean inhibitory concentration (IC50): 2.8 x 10(-9) M], which was not blocked by phentolamine (10(-6) M), hexamethonium (10(-4) M), indomethacin (10(-6) M), nordihydroguaretic acid (10(-6) M), or tetrodotoxin (10(-6) M). The inhibitory effect of neurotensin during CCH stimulation was blocked concentration dependently in the presence of the K(+)-channel blocker apamin. By contrast, other K(+)-channel blockers such as 9-aminoacridine (10(-6) M to 3 x 10(-5) M), 4-aminopyridine (10(-4) M to 5 x 10(-3) M), tetraethylammonium (10(-4) M to 10(-1) M), or glibenclamide (10(-5) M) were ineffective. The presence of the Ca(2+)-channel antagonist nitrendipine (IC50: 2.4 x 10(-9) M) or verapamil (IC50: 1.1 x 10(-7) M) also blocked the neurotensin inhibitory effect. Ileal contraction, induced by the Ca(2+)-channel activator BAY K 8644 (10(-7) M), was completely inhibited by neurotensin. After depletion of internal Ca2+ stores by repetitive stimulation with CCH and caffeine in Ca(2+)-free buffer, reintroduction of external Ca2+ restored neurotensin inhibition of the contraction induced by CCH. These results demonstrate that the inhibitory effect of neurotensin in rat ileum longitudinal muscle is apamin sensitive and cannot be observed in the presence of the Ca(2+)-channel blockers nitrendipine or verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Mechanisms of neurotensin-induced inhibition in rat ileal smooth muscle. The aim of the present study was to determine the mechanisms of neurotensin-induced inhibition in ileal smooth muscle. Isolated rat ileal smooth muscle strips were stimulated in an organ bath using carbachol (CCH) or by KCl depolarization. Neurotensin produced a concentration-dependent inhibition of muscle contraction [mean inhibitory concentration (IC50): 2.8 x 10(-9) M], which was not blocked by phentolamine (10(-6) M), hexamethonium (10(-4) M), indomethacin (10(-6) M), nordihydroguaretic acid (10(-6) M), or tetrodotoxin (10(-6) M). The inhibitory effect of neurotensin during CCH stimulation was blocked concentration dependently in the presence of the K(+)-channel blocker apamin. By contrast, other K(+)-channel blockers such as 9-aminoacridine (10(-6) M to 3 x 10(-5) M), 4-aminopyridine (10(-4) M to 5 x 10(-3) M), tetraethylammonium (10(-4) M to 10(-1) M), or glibenclamide (10(-5) M) were ineffective. The presence of the Ca(2+)-channel antagonist nitrendipine (IC50: 2.4 x 10(-9) M) or verapamil (IC50: 1.1 x 10(-7) M) also blocked the neurotensin inhibitory effect. Ileal contraction, induced by the Ca(2+)-channel activator BAY K 8644 (10(-7) M), was completely inhibited by neurotensin. After depletion of internal Ca2+ stores by repetitive stimulation with CCH and caffeine in Ca(2+)-free buffer, reintroduction of external Ca2+ restored neurotensin inhibition of the contraction induced by CCH. These results demonstrate that the inhibitory effect of neurotensin in rat ileum longitudinal muscle is apamin sensitive and cannot be observed in the presence of the Ca(2+)-channel blockers nitrendipine or verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279985", "title": "Cation channels in basolateral membranes of sheep parotid secretory cells.", "content": "We observed 240-pS K+ channels in 63% of cell-attached patches, and 30-pS K+ channels were observed in 95% of cell-attached patches. The 240-pS K+ channel had the relative permeability sequence of K+ (1) = Rb+ (1) > Cs+ (0.3) >> Na+ (0.03) and the relative conductance sequence of K+ (1) > Rb+ (0.22) > Cs+ (0.05) > Na+ (0). It was activated by intracellular free Ca2+ and by depolarization. It was blocked by 10 mmol/l tetraethylammonium (TEA) applied extracellularly. The 30-pS K+ channel had the relative permeability sequence of K+ (1) = Rb+ (1) > Cs+ (> Na+ (< 0.09) and the relative conductance sequence of K+ (1) > Rb+ (0.45) > Cs+ (0) = Na+ (0). Its activity was not sensitive to cytosolic free Ca2+ or membrane potential, and it was not blocked by 10 mmol/l TEA extracellularly. Acetylcholine (10 mumol/l) activated the 240-pS voltage-activated and Ca(2+)-activated K+ channels but did not activate the 30-pS K+ channels. We conclude that the 30-pS K+ channel probably determines the properties of the basolateral membrane in unstimulated sheep parotid secretory cells, whereas the 240-pS voltage-activated and Ca(2+)-activated K+ channel may be important during parasympathomimetic stimulation.", "contents": "Cation channels in basolateral membranes of sheep parotid secretory cells. We observed 240-pS K+ channels in 63% of cell-attached patches, and 30-pS K+ channels were observed in 95% of cell-attached patches. The 240-pS K+ channel had the relative permeability sequence of K+ (1) = Rb+ (1) > Cs+ (0.3) >> Na+ (0.03) and the relative conductance sequence of K+ (1) > Rb+ (0.22) > Cs+ (0.05) > Na+ (0). It was activated by intracellular free Ca2+ and by depolarization. It was blocked by 10 mmol/l tetraethylammonium (TEA) applied extracellularly. The 30-pS K+ channel had the relative permeability sequence of K+ (1) = Rb+ (1) > Cs+ (> Na+ (< 0.09) and the relative conductance sequence of K+ (1) > Rb+ (0.45) > Cs+ (0) = Na+ (0). Its activity was not sensitive to cytosolic free Ca2+ or membrane potential, and it was not blocked by 10 mmol/l TEA extracellularly. Acetylcholine (10 mumol/l) activated the 240-pS voltage-activated and Ca(2+)-activated K+ channels but did not activate the 30-pS K+ channels. We conclude that the 30-pS K+ channel probably determines the properties of the basolateral membrane in unstimulated sheep parotid secretory cells, whereas the 240-pS voltage-activated and Ca(2+)-activated K+ channel may be important during parasympathomimetic stimulation."} {"id": "PMID:1279986", "title": "Immunocytochemical characterization of Na(+)-H+ exchanger isoform NHE-1 in rabbit kidney.", "content": "We have recently isolated cDNAs encoding a Na(+)-H+ exchanger isoform, referred to as NHE-1, from rabbit kidney and LLC-PK1 cells. To identify the NHE-1 protein and to establish its cellular and subcellular localization in the rabbit kidney, we prepared antibodies to a NHE-1 fusion protein. cDNA encoding the COOH-terminal 41 amino acids of NHE-1 was subcloned into a maltose-binding protein vector and the purified fusion protein (FP347A) used to immunize guinea pigs. To identify the NHE-1 protein, we performed Western blot analysis against membrane fractions prepared from rabbit renal cortex. Anti-FP347A antibody specifically reacted with a polypeptide with an apparent molecular mass of 100-110 kDa that was enriched in basolateral membrane fractions. When indirect immunofluorescence was performed on semithin (0.5 micron) cryosections of paraformaldehyde-lysine-periodate-fixed rabbit kidney, anti-FP347A specifically stained the basolateral plasma membrane of cells of the proximal tubule, thick ascending limb, and distal convoluted tubule. Anti-FP347A similarly stained connecting tubule cells and principal cells. No staining was detected on the apical membrane of any cells of the rabbit nephron. We conclude that NHE-1 is a 100- to 110-kDa protein expressed on the basolateral membrane of multiple nephron segments.", "contents": "Immunocytochemical characterization of Na(+)-H+ exchanger isoform NHE-1 in rabbit kidney. We have recently isolated cDNAs encoding a Na(+)-H+ exchanger isoform, referred to as NHE-1, from rabbit kidney and LLC-PK1 cells. To identify the NHE-1 protein and to establish its cellular and subcellular localization in the rabbit kidney, we prepared antibodies to a NHE-1 fusion protein. cDNA encoding the COOH-terminal 41 amino acids of NHE-1 was subcloned into a maltose-binding protein vector and the purified fusion protein (FP347A) used to immunize guinea pigs. To identify the NHE-1 protein, we performed Western blot analysis against membrane fractions prepared from rabbit renal cortex. Anti-FP347A antibody specifically reacted with a polypeptide with an apparent molecular mass of 100-110 kDa that was enriched in basolateral membrane fractions. When indirect immunofluorescence was performed on semithin (0.5 micron) cryosections of paraformaldehyde-lysine-periodate-fixed rabbit kidney, anti-FP347A specifically stained the basolateral plasma membrane of cells of the proximal tubule, thick ascending limb, and distal convoluted tubule. Anti-FP347A similarly stained connecting tubule cells and principal cells. No staining was detected on the apical membrane of any cells of the rabbit nephron. We conclude that NHE-1 is a 100- to 110-kDa protein expressed on the basolateral membrane of multiple nephron segments."} {"id": "PMID:1279987", "title": "Modulation of tumor necrosis factor-induced increase in renal (LLC-PK1) transepithelial permeability.", "content": "Tumor necrosis factor-alpha (TNF) causes a spontaneously reversible increase in tight junction permeability. TNF was the only cytokine tested that produced this effect. The effect on transepithelial permeability proceeds in four distinct phases: 1) a 60- to 90-min delay from time of application of TNF, 2) a rapid decrease in transepithelial resistance, 3) a recovery of transepithelial resistance to control level within 1 h, and 4) a further increase of transepithelial resistance above control levels. The recovery of transepithelial resistance occurs with or without TNF in the culture medium. Different protein kinase inhibitors affected different phases of this overall process. The tyrosine kinase inhibitor genistein significantly blocked the TNF effect. Neither transcription nor protein synthesis was required for transepithelial permeability to increase, but were required for the recovery. After the tight junctions have opened at 2 h in response to TNF, a second application of TNF will not produce the effect again for at least 12 h. The tight junctions will, however, open in response to phorbol esters during this time frame. Electron microscopy studies using apically applied ruthenium red suggest that TNF action results in < 10% of the junctions having increased permeability at any given time during the resistance decrease. The role of epithelial barrier permeability changes in TNF action in vivo is discussed.", "contents": "Modulation of tumor necrosis factor-induced increase in renal (LLC-PK1) transepithelial permeability. Tumor necrosis factor-alpha (TNF) causes a spontaneously reversible increase in tight junction permeability. TNF was the only cytokine tested that produced this effect. The effect on transepithelial permeability proceeds in four distinct phases: 1) a 60- to 90-min delay from time of application of TNF, 2) a rapid decrease in transepithelial resistance, 3) a recovery of transepithelial resistance to control level within 1 h, and 4) a further increase of transepithelial resistance above control levels. The recovery of transepithelial resistance occurs with or without TNF in the culture medium. Different protein kinase inhibitors affected different phases of this overall process. The tyrosine kinase inhibitor genistein significantly blocked the TNF effect. Neither transcription nor protein synthesis was required for transepithelial permeability to increase, but were required for the recovery. After the tight junctions have opened at 2 h in response to TNF, a second application of TNF will not produce the effect again for at least 12 h. The tight junctions will, however, open in response to phorbol esters during this time frame. Electron microscopy studies using apically applied ruthenium red suggest that TNF action results in < 10% of the junctions having increased permeability at any given time during the resistance decrease. The role of epithelial barrier permeability changes in TNF action in vivo is discussed."} {"id": "PMID:1279988", "title": "Physical and physiological characteristics of pressure-driven hemorrhage.", "content": "Research on hemorrhage has concentrated on its effects rather than the manner of occurrence. A new experimental method in which the rate of bleeding is a function of prevailing arterial pressure is proposed and described. The effects of standard crystalloid volume expansion and of small volume hypertonic treatment on this protocol are demonstrated. In pressure-driven hemorrhage, survival time and the decay of arterial pressure, cardiac output, oxygen consumption, and base excess are functions of the bleeding rate, but plasma proteins and hematocrits are independent. The decay of arterial pressure is also a complex function of blood volume deficit, but this relation is not dependent on the rate of blood removal. Volume expansion induces a recovery of circulatory function despite enhanced blood loss. A comparison between equiosmolar solutions of hypertonic sodium chloride and acetate shows that acetate produces a smaller pressor (hence less blood loss) but larger blood flow (hence higher O2 availability) effect. The possible importance of the isochloremic nature of the response to acetate is highlighted.", "contents": "Physical and physiological characteristics of pressure-driven hemorrhage. Research on hemorrhage has concentrated on its effects rather than the manner of occurrence. A new experimental method in which the rate of bleeding is a function of prevailing arterial pressure is proposed and described. The effects of standard crystalloid volume expansion and of small volume hypertonic treatment on this protocol are demonstrated. In pressure-driven hemorrhage, survival time and the decay of arterial pressure, cardiac output, oxygen consumption, and base excess are functions of the bleeding rate, but plasma proteins and hematocrits are independent. The decay of arterial pressure is also a complex function of blood volume deficit, but this relation is not dependent on the rate of blood removal. Volume expansion induces a recovery of circulatory function despite enhanced blood loss. A comparison between equiosmolar solutions of hypertonic sodium chloride and acetate shows that acetate produces a smaller pressor (hence less blood loss) but larger blood flow (hence higher O2 availability) effect. The possible importance of the isochloremic nature of the response to acetate is highlighted."} {"id": "PMID:1279989", "title": "Attenuation of postischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran.", "content": "The underlying mechanisms of the beneficial therapeutic effects of small-volume resuscitation with hyperosmolar solutions for treatment of hypovolemic shock are still poorly understood. Using the dorsal skinfold chamber model and intravital fluorescence microscopy, we investigated the effects of hyperosmolar saline dextran on ischemia-reperfusion injury in striated skin muscle of awake normovolemic golden hamsters. Test solutions (4 ml/kg body wt i.v.) were administered 2 min before reperfusion after 4 h of pressure-induced ischemia. In animals receiving 0.9% saline (control), we observed a drastic enhancement of leukocyte rolling along and sticking to the endothelium of postcapillary venules 0.5 h after reperfusion. Postischemic leukocyte rolling and sticking were significantly reduced when animals were treated with 7.2% saline alone (HSS), 10% Dextran 60 in 0.9% saline (HDS), or 10% Dextran 60 in 7.2% saline (HHS). In control animals, capillary perfusion was reduced to approximately 60% of preischemic values 0.5 h after reperfusion. Concomitantly, leakage of the macromolecule fluorescein isothiocyanate-dextran (5 mg in 0.1 ml saline i.v., M(r) 150,000) into the perivascular space increased from 0% before ischemia to approximately 12% at 0.5 h reperfusion. In contrast, when animals were treated with HSS, HDS, or HHS before reperfusion, capillary perfusion decreased to a significantly minor extent of approximately 15%, and macromolecular leakage was slightly increased to approximately 5%. Our results suggest that hyperosmolar saline dextran effectively attenuates postischemic microvascular disturbances elicited by ischemia-reperfusion, presumably through reduction of postischemic leukocyte-endothelium interaction and capillary swelling.", "contents": "Attenuation of postischemic microvascular disturbances in striated muscle by hyperosmolar saline dextran. The underlying mechanisms of the beneficial therapeutic effects of small-volume resuscitation with hyperosmolar solutions for treatment of hypovolemic shock are still poorly understood. Using the dorsal skinfold chamber model and intravital fluorescence microscopy, we investigated the effects of hyperosmolar saline dextran on ischemia-reperfusion injury in striated skin muscle of awake normovolemic golden hamsters. Test solutions (4 ml/kg body wt i.v.) were administered 2 min before reperfusion after 4 h of pressure-induced ischemia. In animals receiving 0.9% saline (control), we observed a drastic enhancement of leukocyte rolling along and sticking to the endothelium of postcapillary venules 0.5 h after reperfusion. Postischemic leukocyte rolling and sticking were significantly reduced when animals were treated with 7.2% saline alone (HSS), 10% Dextran 60 in 0.9% saline (HDS), or 10% Dextran 60 in 7.2% saline (HHS). In control animals, capillary perfusion was reduced to approximately 60% of preischemic values 0.5 h after reperfusion. Concomitantly, leakage of the macromolecule fluorescein isothiocyanate-dextran (5 mg in 0.1 ml saline i.v., M(r) 150,000) into the perivascular space increased from 0% before ischemia to approximately 12% at 0.5 h reperfusion. In contrast, when animals were treated with HSS, HDS, or HHS before reperfusion, capillary perfusion decreased to a significantly minor extent of approximately 15%, and macromolecular leakage was slightly increased to approximately 5%. Our results suggest that hyperosmolar saline dextran effectively attenuates postischemic microvascular disturbances elicited by ischemia-reperfusion, presumably through reduction of postischemic leukocyte-endothelium interaction and capillary swelling."} {"id": "PMID:1279990", "title": "Anisotropic conduction and reentry in perfused epicardium of rabbit left ventricle.", "content": "An experimental model of anisotropy was developed, consisting of a thin layer (1 mm) of perfused ventricular epicardium created by cryodestruction of the interventricular septum and the inner four-fifths of the free wall of the left ventricle. The electrophysiological properties of the 1-mm-thick surviving layer were the same as before freezing. Epicardial conduction was mapped with a 192-fold mapping electrode (spatial resolution 1 mm). In the intact ventricle transverse conduction was interrupted near the site of stimulation by epicardial breakthrough of faster intramural wavefronts, whereas in the thin epicardial layer transverse conduction proceeded over a much longer distance, resulting in enlargement of the area of effective anisotropy. Induction of premature beats or incremental pacing resulted in the development of lines of transverse conduction block. The occurrence of transverse conduction block, however, only rarely led to reentry, because fast longitudinal activation of the tissue distal to the line of block provided insufficient delay for the fibers proximal to the line of block to restore their excitability. Initiation of reentry was associated with the development of longitudinal arcs of conduction block during which the area distal to the line of block was activated by a slowly propagating transverse wavefront providing a longer delay for the proximal fibers to restore their excitability. In conclusion, thin layers of myocardium may provide a substrate for reentry because of enlargement of the effective area of anisotropy.", "contents": "Anisotropic conduction and reentry in perfused epicardium of rabbit left ventricle. An experimental model of anisotropy was developed, consisting of a thin layer (1 mm) of perfused ventricular epicardium created by cryodestruction of the interventricular septum and the inner four-fifths of the free wall of the left ventricle. The electrophysiological properties of the 1-mm-thick surviving layer were the same as before freezing. Epicardial conduction was mapped with a 192-fold mapping electrode (spatial resolution 1 mm). In the intact ventricle transverse conduction was interrupted near the site of stimulation by epicardial breakthrough of faster intramural wavefronts, whereas in the thin epicardial layer transverse conduction proceeded over a much longer distance, resulting in enlargement of the area of effective anisotropy. Induction of premature beats or incremental pacing resulted in the development of lines of transverse conduction block. The occurrence of transverse conduction block, however, only rarely led to reentry, because fast longitudinal activation of the tissue distal to the line of block provided insufficient delay for the fibers proximal to the line of block to restore their excitability. Initiation of reentry was associated with the development of longitudinal arcs of conduction block during which the area distal to the line of block was activated by a slowly propagating transverse wavefront providing a longer delay for the proximal fibers to restore their excitability. In conclusion, thin layers of myocardium may provide a substrate for reentry because of enlargement of the effective area of anisotropy."} {"id": "PMID:1279991", "title": "Translation of heart preproenkephalin mRNA and secretion of enkephalin peptides from cultured cardiac myocytes.", "content": "Rat ventricular cardiac muscle has previously been shown to contain exceptionally high levels of preproenkephalin mRNA (ppEnk mRNA). We have recently determined that the level of ppEnk mRNA is developmentally and hormonally regulated in rat ventricular cardiac muscle tissue and in cultured myocytes (J. P. Springhorn and W. C. Claycomb. Biochem. J. 258: 73-77, 1989). We demonstrate in the current study that heart ppEnk mRNA is structurally identical at the 5' end to brain ppEnk mRNA using a ribonuclease protection assay and that heart ppEnk mRNA can be translated in vitro using a rabbit reticulocyte lysate system. In vitro synthesized preproenkephalin peptides were immunoprecipitated with a polyclonal antibody directed to the carboxy-terminal seven amino acids of preproenkephalin. We have also established by radioimmunoassay that enkephalin-containing peptides are secreted from cultured neonatal and adult rat ventricular cardiac muscle cells. This secretion is linear with respect to time and can be stimulated by phorbol 12-myristate 13-acetate (PMA) and adenosine 3',5'-cyclic monophosphate (cAMP). It was determined by column chromatography that cAMP induced neonatal rat ventricular cardiac muscle cells to secrete Met5-enkephalin-Arg6-Phe7, whereas PMA plus 3-isobutyl-1-methylxanthine induced adult rat ventricular cardiac muscle cells to secrete Met5-enkephalin. These studies establish that ventricular heart muscle ppEnk mRNA can be translated and that enkephalin peptides are secreted from ventricular cardiac muscle cells.", "contents": "Translation of heart preproenkephalin mRNA and secretion of enkephalin peptides from cultured cardiac myocytes. Rat ventricular cardiac muscle has previously been shown to contain exceptionally high levels of preproenkephalin mRNA (ppEnk mRNA). We have recently determined that the level of ppEnk mRNA is developmentally and hormonally regulated in rat ventricular cardiac muscle tissue and in cultured myocytes (J. P. Springhorn and W. C. Claycomb. Biochem. J. 258: 73-77, 1989). We demonstrate in the current study that heart ppEnk mRNA is structurally identical at the 5' end to brain ppEnk mRNA using a ribonuclease protection assay and that heart ppEnk mRNA can be translated in vitro using a rabbit reticulocyte lysate system. In vitro synthesized preproenkephalin peptides were immunoprecipitated with a polyclonal antibody directed to the carboxy-terminal seven amino acids of preproenkephalin. We have also established by radioimmunoassay that enkephalin-containing peptides are secreted from cultured neonatal and adult rat ventricular cardiac muscle cells. This secretion is linear with respect to time and can be stimulated by phorbol 12-myristate 13-acetate (PMA) and adenosine 3',5'-cyclic monophosphate (cAMP). It was determined by column chromatography that cAMP induced neonatal rat ventricular cardiac muscle cells to secrete Met5-enkephalin-Arg6-Phe7, whereas PMA plus 3-isobutyl-1-methylxanthine induced adult rat ventricular cardiac muscle cells to secrete Met5-enkephalin. These studies establish that ventricular heart muscle ppEnk mRNA can be translated and that enkephalin peptides are secreted from ventricular cardiac muscle cells."} {"id": "PMID:1279992", "title": "Action potential conduction between guinea pig ventricular cells can be modulated by calcium current.", "content": "We used cell pairs electrically coupled with relatively high intercellular resistance to investigate the involvement of calcium current in the origin of the source current during the conduction process of the action potential (AP). Three interventions were used to reduce the calcium current: a specific calcium channel blocker [nifedipine (NIF)], premature stimulation, and increments in the frequency of stimulation of the cell. The ionic membrane current (Iion) after the peak of the AP of the stimulated cell was positive and small when the cell was uncoupled. However, when the stimulated cell was coupled to a cell model or to another cell, Iion during this period became negative and large to supply the coupling current. A rapid early repolarization of the AP occurred in the stimulated cell because of the removal of charge from the stimulated cell. NIF decreased the magnitude of the net negative Iion during this period and caused a more rapid early repolarization in the stimulated cell. NIF increased the delay between the activations of two coupled cells at a given coupling resistance (Rc) but decreased the longest delay that could be produced without conduction failure for a given cell pair. The highest Rc below which conduction of AP occurred was also decreased by NIF. Premature stimulation and an increase of the stimulation frequency also caused an increase in the extent of the early repolarization and increased the delay between two cell activations at a given Rc. Conduction block occurred with sufficient prematurity or at a sufficiently high frequency of stimulation even though activation of the stimulated cell occurred for each stimulus. The Iion that flows during the early plateau phase of the AP in the stimulated cell became negative and significantly large by coupling two cardiac cells together. This current flow is a major component needed to supply the coupling current through the intercellular resistance. The decrease of calcium current caused a decrease in the magnitude of this net inward ionic current, resulting in an increase of the rate of early repolarization and an increase in the conduction delay between two cells at a given Rc. These results suggest the involvement of calcium current in the conduction process when cells are coupled at relatively high Rc.", "contents": "Action potential conduction between guinea pig ventricular cells can be modulated by calcium current. We used cell pairs electrically coupled with relatively high intercellular resistance to investigate the involvement of calcium current in the origin of the source current during the conduction process of the action potential (AP). Three interventions were used to reduce the calcium current: a specific calcium channel blocker [nifedipine (NIF)], premature stimulation, and increments in the frequency of stimulation of the cell. The ionic membrane current (Iion) after the peak of the AP of the stimulated cell was positive and small when the cell was uncoupled. However, when the stimulated cell was coupled to a cell model or to another cell, Iion during this period became negative and large to supply the coupling current. A rapid early repolarization of the AP occurred in the stimulated cell because of the removal of charge from the stimulated cell. NIF decreased the magnitude of the net negative Iion during this period and caused a more rapid early repolarization in the stimulated cell. NIF increased the delay between the activations of two coupled cells at a given coupling resistance (Rc) but decreased the longest delay that could be produced without conduction failure for a given cell pair. The highest Rc below which conduction of AP occurred was also decreased by NIF. Premature stimulation and an increase of the stimulation frequency also caused an increase in the extent of the early repolarization and increased the delay between two cell activations at a given Rc. Conduction block occurred with sufficient prematurity or at a sufficiently high frequency of stimulation even though activation of the stimulated cell occurred for each stimulus. The Iion that flows during the early plateau phase of the AP in the stimulated cell became negative and significantly large by coupling two cardiac cells together. This current flow is a major component needed to supply the coupling current through the intercellular resistance. The decrease of calcium current caused a decrease in the magnitude of this net inward ionic current, resulting in an increase of the rate of early repolarization and an increase in the conduction delay between two cells at a given Rc. These results suggest the involvement of calcium current in the conduction process when cells are coupled at relatively high Rc."} {"id": "PMID:1279993", "title": "Modulation of glucose metabolic response to endotoxin by granulocyte colony-stimulating factor.", "content": "The present study examines whether in vivo administration of granulocyte colony-stimulating factor (G-CSF) and the resultant neutrophilia alters basal glucose metabolism or modulates the glucose metabolic response to a subsequent endotoxin [lipopolysaccharide (LPS)] challenge. Rats were injected with human recombinant G-CSF (50 micrograms/kg sc) twice daily for 2 days preceding an injection of LPS. Animals treated with G-CSF showed an eightfold increase in blood polymorphonuclear leukocytes (PMNs) but no detectable changes in hemodynamics or glucose metabolism. In control animals, LPS transiently decreased circulating PMN number, but by 4 h neutrophils had returned to control levels. LPS produced a greater reduction in circulating neutrophils in G-CSF-treated animals, which did not return to pretreatment levels by 4 h. G-CSF also produced marked changes in the glucose metabolic response to LPS. Rates of whole body glucose production and utilization in both control and G-CSF-treated rats were rapidly increased by LPS; however, the increment in glucose flux was 55-100% greater in the latter group. The enhanced rate of hepatic glucose production in this group occurred despite lower plasma levels of lactate and glucagon. The elevated rate of whole body glucose utilization was attributable to the G-CSF-enhanced LPS-induced increase in glucose uptake by the ileum, spleen, liver, and lung. Furthermore, LPS increased glucose uptake by skeletal muscle in G-CSF-treated rats but not in control animals. The enhanced glucose disposal in G-CSF-treated rats was not mediated by increases in plasma glucose or insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Modulation of glucose metabolic response to endotoxin by granulocyte colony-stimulating factor. The present study examines whether in vivo administration of granulocyte colony-stimulating factor (G-CSF) and the resultant neutrophilia alters basal glucose metabolism or modulates the glucose metabolic response to a subsequent endotoxin [lipopolysaccharide (LPS)] challenge. Rats were injected with human recombinant G-CSF (50 micrograms/kg sc) twice daily for 2 days preceding an injection of LPS. Animals treated with G-CSF showed an eightfold increase in blood polymorphonuclear leukocytes (PMNs) but no detectable changes in hemodynamics or glucose metabolism. In control animals, LPS transiently decreased circulating PMN number, but by 4 h neutrophils had returned to control levels. LPS produced a greater reduction in circulating neutrophils in G-CSF-treated animals, which did not return to pretreatment levels by 4 h. G-CSF also produced marked changes in the glucose metabolic response to LPS. Rates of whole body glucose production and utilization in both control and G-CSF-treated rats were rapidly increased by LPS; however, the increment in glucose flux was 55-100% greater in the latter group. The enhanced rate of hepatic glucose production in this group occurred despite lower plasma levels of lactate and glucagon. The elevated rate of whole body glucose utilization was attributable to the G-CSF-enhanced LPS-induced increase in glucose uptake by the ileum, spleen, liver, and lung. Furthermore, LPS increased glucose uptake by skeletal muscle in G-CSF-treated rats but not in control animals. The enhanced glucose disposal in G-CSF-treated rats was not mediated by increases in plasma glucose or insulin concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279994", "title": "Characterization of a natural human antibody with anti-galactosyl(alpha 1-2)galactose specificity that is present at high titers in chronic Trypanosoma cruzi infection.", "content": "An antibody reactive with the galactosyl(alpha 1-2)galactose [gal(alpha 1-2)gal] epitope was characterized in human sera by enzyme-linked immunosorbent assay, red blood cell (RBC) and laminin absorption, and oligosaccharide inhibition. This antibody was found evenly distributed between the IgG and IgM classes and was present at high titers in the serum of all normal adults studied, but in 75% of children less than three years of age, it was observed at the lower limit of detection, and gradually increased to adult levels by the age of six. Although this antibody bound to gal(alpha 1-3)gal-linked synthetic antigens, it did not bind to the same residues present in rabbit, rat, and guinea pig RBC or in murine laminin or nidogen. These latter results, plus the fact that antigen-antibody binding was strongly blocked by gal(alpha 1-2)gal but not by methyl-alpha-galactopyranoside or melibiose, suggest that this antibody is indeed different from anti-gal(alpha 1-3)gal antibody. Anti-gal(alpha 1-2)gal antibody levels were significantly elevated in 66% of patients with chronic chagasic cardiomyopathy, but were not elevated in patients with different clinical forms of leishmaniasis, Trypanosoma rangeli-infected patients, or in patients with 15 other infectious and inflammatory diseases. Gal(alpha 1-2)gal antibodies did not absorb to intact T. cruzi parasites, but absorbed strongly to trypomastigote and epimastigote sonicates, suggesting some masking of reactive epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Characterization of a natural human antibody with anti-galactosyl(alpha 1-2)galactose specificity that is present at high titers in chronic Trypanosoma cruzi infection. An antibody reactive with the galactosyl(alpha 1-2)galactose [gal(alpha 1-2)gal] epitope was characterized in human sera by enzyme-linked immunosorbent assay, red blood cell (RBC) and laminin absorption, and oligosaccharide inhibition. This antibody was found evenly distributed between the IgG and IgM classes and was present at high titers in the serum of all normal adults studied, but in 75% of children less than three years of age, it was observed at the lower limit of detection, and gradually increased to adult levels by the age of six. Although this antibody bound to gal(alpha 1-3)gal-linked synthetic antigens, it did not bind to the same residues present in rabbit, rat, and guinea pig RBC or in murine laminin or nidogen. These latter results, plus the fact that antigen-antibody binding was strongly blocked by gal(alpha 1-2)gal but not by methyl-alpha-galactopyranoside or melibiose, suggest that this antibody is indeed different from anti-gal(alpha 1-3)gal antibody. Anti-gal(alpha 1-2)gal antibody levels were significantly elevated in 66% of patients with chronic chagasic cardiomyopathy, but were not elevated in patients with different clinical forms of leishmaniasis, Trypanosoma rangeli-infected patients, or in patients with 15 other infectious and inflammatory diseases. Gal(alpha 1-2)gal antibodies did not absorb to intact T. cruzi parasites, but absorbed strongly to trypomastigote and epimastigote sonicates, suggesting some masking of reactive epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1279995", "title": "Recognition of Plasmodium falciparum asexual stage antigens by antibodies in sera from people exposed to Plasmodium vivax.", "content": "An analysis of Plasmodium falciparum antigen-specific antibodies was performed on 44 serum samples from Guatemala, a region endemic for P. vivax. Most sera showed positive reactivity to P. falciparum asexual stage antigens by indirect immunofluorescent assay, enzyme-linked immunosorbent assay, and immunoprecipitation analysis using biosynthetically labeled parasites. Although several antigens were recognized by these sera, proteins with molecular weights of 195 kD, 140 kD, and in the range of 70-80 kD were strongly recognized by many of the sera studied. No such reactivity was observed for any of the surface antigens in the male and female gametes and zygotes of P. falciparum. These studies suggest that P. vivax and P. falciparum, two major human parasites, may share certain epitopes in several antigens of immunologic significance.", "contents": "Recognition of Plasmodium falciparum asexual stage antigens by antibodies in sera from people exposed to Plasmodium vivax. An analysis of Plasmodium falciparum antigen-specific antibodies was performed on 44 serum samples from Guatemala, a region endemic for P. vivax. Most sera showed positive reactivity to P. falciparum asexual stage antigens by indirect immunofluorescent assay, enzyme-linked immunosorbent assay, and immunoprecipitation analysis using biosynthetically labeled parasites. Although several antigens were recognized by these sera, proteins with molecular weights of 195 kD, 140 kD, and in the range of 70-80 kD were strongly recognized by many of the sera studied. No such reactivity was observed for any of the surface antigens in the male and female gametes and zygotes of P. falciparum. These studies suggest that P. vivax and P. falciparum, two major human parasites, may share certain epitopes in several antigens of immunologic significance."} {"id": "PMID:1279996", "title": "Characterization of Borrelia burgdorferi isolated from Ixodes persulcatus and Ixodes ovatus ticks in Japan.", "content": "The Lyme disease spirochete Borrelia burgdorferi was detected in the adult stage of the ixodid ticks Ixodes persulcatus and I. ovatus collected in various localities in Japan. The total prevalence values were 16.6% of 777 I. persulcatus and 23.6% of 687 I. ovatus. Sixty-two (63.9%) of 97 isolates from I. persulcatus contained the 30-34-kD heterogeneous outer surface protein A (OspA) that reacted with monoclonal antibody H5332. In contrast, all 128 isolates from I. ovatus were homogeneous with regard to the type of 30-kD OspA protein, and were different from the I. persulcatus isolates in their protein composition. These data suggest that the transmission cycle of B. burgdorferi in I. ovatus is not related to that in I. persulcatus. No cases of Lyme disease transmitted by I. ovatus have been confirmed in Japan, in spite of the abundance of human tick bites by this species. Accordingly, the spirochetes of I. ovatus are thought to be a variant of B. burgdorferi with low virulence.", "contents": "Characterization of Borrelia burgdorferi isolated from Ixodes persulcatus and Ixodes ovatus ticks in Japan. The Lyme disease spirochete Borrelia burgdorferi was detected in the adult stage of the ixodid ticks Ixodes persulcatus and I. ovatus collected in various localities in Japan. The total prevalence values were 16.6% of 777 I. persulcatus and 23.6% of 687 I. ovatus. Sixty-two (63.9%) of 97 isolates from I. persulcatus contained the 30-34-kD heterogeneous outer surface protein A (OspA) that reacted with monoclonal antibody H5332. In contrast, all 128 isolates from I. ovatus were homogeneous with regard to the type of 30-kD OspA protein, and were different from the I. persulcatus isolates in their protein composition. These data suggest that the transmission cycle of B. burgdorferi in I. ovatus is not related to that in I. persulcatus. No cases of Lyme disease transmitted by I. ovatus have been confirmed in Japan, in spite of the abundance of human tick bites by this species. Accordingly, the spirochetes of I. ovatus are thought to be a variant of B. burgdorferi with low virulence."} {"id": "PMID:1279997", "title": "Characteristics of cystic neoplasms of the pancreas and results of aggressive surgical treatment.", "content": "Twenty-one patients with pancreatic cystic neoplasms (PCNs) were treated from 1970 to 1991. Their mean age was 54 years (range: 30 to 78 years), and 15 (71%) were women. Symptoms were present for a mean of 18 months (range: 5 to 60 months) and included pain (95%), abdominal mass (52%), weight loss (38%), and jaundice (14%). Nine patients had had previous operations and were either misdiagnosed or incorrectly treated; another seven patients had preoperative misdiagnoses of pseudocysts. There were six (29%) serous cystadenomas and two (10%) mucinous cystadenomas. These were treated by excision (n = 2), distal pancreatectomy (n = 5), or pancreatoduodenectomy (n = 1). No recurrence or malignant degeneration occurred during the mean follow-up of 9 years (range: 1 to 19 years). There were 13 (62%) patients with mucinous cystadenocarcinomas. Of these 13 patients, 3 had unresectable tumors, underwent palliative procedures, and died at 4, 7, and 9 months, respectively. Ten patients underwent pancreatoduodenectomy (n = 4), distal (n = 4) pancreatectomy, or total (n = 2) pancreatectomy: 1 died of recurrence (survival: 8 months), and the remaining 9 patients had a mean survival of 6 years (range: 2 to 20 years) without recurrence. This experience suggests that patients with PCNs have a good prognosis and are curable if the cysts are diagnosed early and completely resected.", "contents": "Characteristics of cystic neoplasms of the pancreas and results of aggressive surgical treatment. Twenty-one patients with pancreatic cystic neoplasms (PCNs) were treated from 1970 to 1991. Their mean age was 54 years (range: 30 to 78 years), and 15 (71%) were women. Symptoms were present for a mean of 18 months (range: 5 to 60 months) and included pain (95%), abdominal mass (52%), weight loss (38%), and jaundice (14%). Nine patients had had previous operations and were either misdiagnosed or incorrectly treated; another seven patients had preoperative misdiagnoses of pseudocysts. There were six (29%) serous cystadenomas and two (10%) mucinous cystadenomas. These were treated by excision (n = 2), distal pancreatectomy (n = 5), or pancreatoduodenectomy (n = 1). No recurrence or malignant degeneration occurred during the mean follow-up of 9 years (range: 1 to 19 years). There were 13 (62%) patients with mucinous cystadenocarcinomas. Of these 13 patients, 3 had unresectable tumors, underwent palliative procedures, and died at 4, 7, and 9 months, respectively. Ten patients underwent pancreatoduodenectomy (n = 4), distal (n = 4) pancreatectomy, or total (n = 2) pancreatectomy: 1 died of recurrence (survival: 8 months), and the remaining 9 patients had a mean survival of 6 years (range: 2 to 20 years) without recurrence. This experience suggests that patients with PCNs have a good prognosis and are curable if the cysts are diagnosed early and completely resected."} {"id": "PMID:1279998", "title": "Diagnostic peritoneal lavage in acute peritonitis.", "content": "Fifty patients were studied prospectively to determine the value of diagnostic peritoneal lavage in the evaluation of acute peritonitis. Forty-five patients had a clinical diagnosis of acute peritonitis based on physical findings, and 5 patients were normal control subjects. All lavages were performed with an open technique in the operating room prior to laparotomy. Lavage fluid was analyzed for white and red blood cell counts, the differential, amylase, protein, bilirubin, and pH. Results were analyzed by multiple logistic regression. Thirty-two of the 45 patients with clinical peritonitis had the diagnosis confirmed at laparotomy. A white blood cell count in the lavage fluid greater than or equal to 200 cells/mm3 was associated with a 99% probability of peritonitis.", "contents": "Diagnostic peritoneal lavage in acute peritonitis. Fifty patients were studied prospectively to determine the value of diagnostic peritoneal lavage in the evaluation of acute peritonitis. Forty-five patients had a clinical diagnosis of acute peritonitis based on physical findings, and 5 patients were normal control subjects. All lavages were performed with an open technique in the operating room prior to laparotomy. Lavage fluid was analyzed for white and red blood cell counts, the differential, amylase, protein, bilirubin, and pH. Results were analyzed by multiple logistic regression. Thirty-two of the 45 patients with clinical peritonitis had the diagnosis confirmed at laparotomy. A white blood cell count in the lavage fluid greater than or equal to 200 cells/mm3 was associated with a 99% probability of peritonitis."} {"id": "PMID:1279999", "title": "Adrenoleukodystrophy in a Chinese boy.", "content": "We report the first Chinese boy with adrenoleukodystrophy (ALD) who presented with hyperpigmentation, behavioral change and demyelination shown in magnetic resonance imaging of the brain. ALD was confirmed by the elevation of very long chain fatty acid in the serum and biochemical evidence of adrenal insufficiency. A trial of special diet with restriction of very long chain fatty acid and addition of glyceryl trierucate/glycerol trioleate oil (GTEO or Lorenzo's oil) failed to prevent clinical deterioration. The child had progressive visual loss and spastic tetraparesis despite dietary manipulation, adrenal steroid replacement and intravenous gammaglobulin treatment.", "contents": "Adrenoleukodystrophy in a Chinese boy. We report the first Chinese boy with adrenoleukodystrophy (ALD) who presented with hyperpigmentation, behavioral change and demyelination shown in magnetic resonance imaging of the brain. ALD was confirmed by the elevation of very long chain fatty acid in the serum and biochemical evidence of adrenal insufficiency. A trial of special diet with restriction of very long chain fatty acid and addition of glyceryl trierucate/glycerol trioleate oil (GTEO or Lorenzo's oil) failed to prevent clinical deterioration. The child had progressive visual loss and spastic tetraparesis despite dietary manipulation, adrenal steroid replacement and intravenous gammaglobulin treatment."} {"id": "PMID:1280000", "title": "Effects of alcohol feeding on synthesis and secretion of apolipoproteins by regenerating rat sciatic nerve.", "content": "The amounts of apolipoprotein (apo) E and A1 released into the culture medium were examined in the regenerating nerves distal to a crush site following chronic alcohol feeding. Cultured minced segments of regenerating nerves taken from rats fed an alcohol-containing liquid diet for 5 weeks released only 50% of apoE but nearly 200% of apoA1 when compared with rats pair-fed with a control diet. The extent of decrease in medium apoE corresponded to the decrease of apoE mRNA in the nerve. Thus, chronic alcohol ingestion affects apoE synthesis of regenerating nerves by changing its mRNA level. On the other hand, apoA1 mRNA remained undetectable in regenerating and intact nerves whether the rats were fed alcohol or not. Furthermore, the amount of apoA1 released by the regenerating nerve into the culture medium was not significantly larger than that present in the nerve tissue prior to incubation. Therefore, it is most likely that apoA1 released by the injured nerve originated from the bloodstream and the increase in apoA1 content seen in the crushed nerve of alcohol-fed rats is due to an enhanced permeability of the nerve-blood barrier. Since the burst of apolipoproteins in the injured nerve is likely to play a role in nerve regeneration, the perturbation of apolipoprotein contents in regenerating nerves by chronic alcohol consumption may contribute to the pathogenesis of alcoholic neuropathy.", "contents": "Effects of alcohol feeding on synthesis and secretion of apolipoproteins by regenerating rat sciatic nerve. The amounts of apolipoprotein (apo) E and A1 released into the culture medium were examined in the regenerating nerves distal to a crush site following chronic alcohol feeding. Cultured minced segments of regenerating nerves taken from rats fed an alcohol-containing liquid diet for 5 weeks released only 50% of apoE but nearly 200% of apoA1 when compared with rats pair-fed with a control diet. The extent of decrease in medium apoE corresponded to the decrease of apoE mRNA in the nerve. Thus, chronic alcohol ingestion affects apoE synthesis of regenerating nerves by changing its mRNA level. On the other hand, apoA1 mRNA remained undetectable in regenerating and intact nerves whether the rats were fed alcohol or not. Furthermore, the amount of apoA1 released by the regenerating nerve into the culture medium was not significantly larger than that present in the nerve tissue prior to incubation. Therefore, it is most likely that apoA1 released by the injured nerve originated from the bloodstream and the increase in apoA1 content seen in the crushed nerve of alcohol-fed rats is due to an enhanced permeability of the nerve-blood barrier. Since the burst of apolipoproteins in the injured nerve is likely to play a role in nerve regeneration, the perturbation of apolipoprotein contents in regenerating nerves by chronic alcohol consumption may contribute to the pathogenesis of alcoholic neuropathy."} {"id": "PMID:1280001", "title": "Reversible paraplegia following coeliac plexus block.", "content": "Permanent paraplegia following coeliac plexus block has been reported on several occasions. We report a case of reversible paraplegia following coeliac plexus block.", "contents": "Reversible paraplegia following coeliac plexus block. Permanent paraplegia following coeliac plexus block has been reported on several occasions. We report a case of reversible paraplegia following coeliac plexus block."} {"id": "PMID:1280002", "title": "Epitope mapping by a method that requires no amino acid sequence information.", "content": "A simple, rapid method of epitope mapping has been developed that avoids the often cumbersome requirement of obtaining amino acid sequence information. The protein antigen is digested with various concentrations of carboxypeptidase into a nearly continuous series of polypeptides of different molecular weights, all containing a common N-terminus. The peptides are separated by polyacrylamide gel electrophoresis and then transferred to nitrocellulose paper. After developing the blot with the antibody to be mapped, a nearly continuous stain is observed extending from the position of the intact antigen to the molecular weight of the smallest N-terminal fragment still containing the antibody's epitope. By noting the molecular weight where the stain terminates, the position of the epitope relative to the N-terminus can be determined. Using this methodology, and taking special precautions to inhibit all endoproteinases in the carboxypeptidase preparation, the previously mapped epitopes of six nonoverlapping antibodies to the erythrocyte anion transporter were confirmed.", "contents": "Epitope mapping by a method that requires no amino acid sequence information. A simple, rapid method of epitope mapping has been developed that avoids the often cumbersome requirement of obtaining amino acid sequence information. The protein antigen is digested with various concentrations of carboxypeptidase into a nearly continuous series of polypeptides of different molecular weights, all containing a common N-terminus. The peptides are separated by polyacrylamide gel electrophoresis and then transferred to nitrocellulose paper. After developing the blot with the antibody to be mapped, a nearly continuous stain is observed extending from the position of the intact antigen to the molecular weight of the smallest N-terminal fragment still containing the antibody's epitope. By noting the molecular weight where the stain terminates, the position of the epitope relative to the N-terminus can be determined. Using this methodology, and taking special precautions to inhibit all endoproteinases in the carboxypeptidase preparation, the previously mapped epitopes of six nonoverlapping antibodies to the erythrocyte anion transporter were confirmed."} {"id": "PMID:1280003", "title": "Antibody-antigen complex formation with immobilized immunoglobulins.", "content": "We have investigated the complex formation between an immobilized monoclonal antibody and antigens that differ in size about 50-fold. As a model system, we used an iodinated progesterone derivative and a progesterone-horseradish peroxidase conjugate as tracer and a monoclonal antibody as binding protein. The antibody was immobilized by four different methods: physical adsorption, chemical binding, and binding via protein G in the absence or presence of a protective protein (gelatin). These investigations have shown that the performance of competitive immunoassays is determined by a combination of factors: (a) the relative size of the analyte and the tracer, (b) the antibody density on the solid matrix, (c) the method of immobilization of the antibody, and (d) the binding constants between antibody-analyte and antibody-tracer. All of these interactions have to be considered in designing an optimal immunoassay. The smaller antigen can form a 3- to 35-fold higher maximal complex density than the larger antigen. Dose-response curves are less affected by the size of the tracer than by the binding constant with the antibody. A large enzyme tracer with a relatively low binding constant can, therefore, provide a more sensitive assay. On the other hand, the increase in complex density achieved with a smaller tracer yields a higher signal that in turn can provide a better signal-to-noise ratio in highly sensitive competitive solid-phase immunoassays. We have suggested a model for antibody immobilization that accounts for the interdependence of tracer size, complex formation, and antibody density. The methods described can be used to design and optimize immunoassays of predefined performance characteristics. The results are particularly useful for converting radioimmunoassays to enzyme immunoassays.", "contents": "Antibody-antigen complex formation with immobilized immunoglobulins. We have investigated the complex formation between an immobilized monoclonal antibody and antigens that differ in size about 50-fold. As a model system, we used an iodinated progesterone derivative and a progesterone-horseradish peroxidase conjugate as tracer and a monoclonal antibody as binding protein. The antibody was immobilized by four different methods: physical adsorption, chemical binding, and binding via protein G in the absence or presence of a protective protein (gelatin). These investigations have shown that the performance of competitive immunoassays is determined by a combination of factors: (a) the relative size of the analyte and the tracer, (b) the antibody density on the solid matrix, (c) the method of immobilization of the antibody, and (d) the binding constants between antibody-analyte and antibody-tracer. All of these interactions have to be considered in designing an optimal immunoassay. The smaller antigen can form a 3- to 35-fold higher maximal complex density than the larger antigen. Dose-response curves are less affected by the size of the tracer than by the binding constant with the antibody. A large enzyme tracer with a relatively low binding constant can, therefore, provide a more sensitive assay. On the other hand, the increase in complex density achieved with a smaller tracer yields a higher signal that in turn can provide a better signal-to-noise ratio in highly sensitive competitive solid-phase immunoassays. We have suggested a model for antibody immobilization that accounts for the interdependence of tracer size, complex formation, and antibody density. The methods described can be used to design and optimize immunoassays of predefined performance characteristics. The results are particularly useful for converting radioimmunoassays to enzyme immunoassays."} {"id": "PMID:1280004", "title": "High-performance anion-exchange chromatography of asparagine-linked oligosaccharides.", "content": "Oligosaccharides released enzymatically by N-glycanase from fetuin, alpha-acid glycoprotein, human chorionic gonadotropin, platelet-derived growth factor, and kallikrein were chromatographed on a polymeric pellicular anion-exchange column at pH values of 5 and 13. Separations occurred into groups of peaks containing the same number of sialic acids with an additional separation dependent upon the nature of the antennary structure present. High pH conditions were required for the optimum separation of fetuin oligosaccharides, while low pH conditions significantly improved resolution of oligosaccharides obtained from the other glycoproteins. The analytical separation of oligosaccharides under conditions of low pH has important implications in the development of chromatographic mapping and identification techniques for N-linked oligosaccharides present on recombinant proteins.", "contents": "High-performance anion-exchange chromatography of asparagine-linked oligosaccharides. Oligosaccharides released enzymatically by N-glycanase from fetuin, alpha-acid glycoprotein, human chorionic gonadotropin, platelet-derived growth factor, and kallikrein were chromatographed on a polymeric pellicular anion-exchange column at pH values of 5 and 13. Separations occurred into groups of peaks containing the same number of sialic acids with an additional separation dependent upon the nature of the antennary structure present. High pH conditions were required for the optimum separation of fetuin oligosaccharides, while low pH conditions significantly improved resolution of oligosaccharides obtained from the other glycoproteins. The analytical separation of oligosaccharides under conditions of low pH has important implications in the development of chromatographic mapping and identification techniques for N-linked oligosaccharides present on recombinant proteins."} {"id": "PMID:1280005", "title": "High-sensitivity analysis of sialyl-oligosaccharide glycosylation sites in glycoproteins by miniaturized tryptic digestion and microcolumn liquid chromatography.", "content": "A highly sensitive analytical procedure was developed to assess the site of glycosylation in a model glycoprotein, bovine fetuin. First, sample cleavage with immobilized trypsin and the peptide map development are accomplished by microcolumn liquid chromatography. Second, the sialic acids content is measured fluorometrically using their precolumn conversion to quinoxaline derivatives. A unique preconcentration system was developed to secure sensitivity of the second measurement.", "contents": "High-sensitivity analysis of sialyl-oligosaccharide glycosylation sites in glycoproteins by miniaturized tryptic digestion and microcolumn liquid chromatography. A highly sensitive analytical procedure was developed to assess the site of glycosylation in a model glycoprotein, bovine fetuin. First, sample cleavage with immobilized trypsin and the peptide map development are accomplished by microcolumn liquid chromatography. Second, the sialic acids content is measured fluorometrically using their precolumn conversion to quinoxaline derivatives. A unique preconcentration system was developed to secure sensitivity of the second measurement."} {"id": "PMID:1280006", "title": "Quantification of gene expression over a wide range by the polymerase chain reaction.", "content": "We investigated the usefulness of the polymerase chain reaction (PCR) method for the relative quantification of gene expression using a simultaneously amplified sequence of beta-actin mRNA as an internal control for the target sequence of tax/rex mRNA of human T-cell leukemia virus type I. The PCR product of the internal control was reduced by delaying the addition of the primers for its sequence. The photostimulated luminescence of the bands was measured with a laser image analyzer, and the values were plotted against the cycle number. The cycle differences between the logarithmic phase of the curves for the target sequence and for beta-actin (delta cycle) showed a linear correlation with the initial concentration of the sample. This method is highly sensitive for evaluating gene expression over a wide range.", "contents": "Quantification of gene expression over a wide range by the polymerase chain reaction. We investigated the usefulness of the polymerase chain reaction (PCR) method for the relative quantification of gene expression using a simultaneously amplified sequence of beta-actin mRNA as an internal control for the target sequence of tax/rex mRNA of human T-cell leukemia virus type I. The PCR product of the internal control was reduced by delaying the addition of the primers for its sequence. The photostimulated luminescence of the bands was measured with a laser image analyzer, and the values were plotted against the cycle number. The cycle differences between the logarithmic phase of the curves for the target sequence and for beta-actin (delta cycle) showed a linear correlation with the initial concentration of the sample. This method is highly sensitive for evaluating gene expression over a wide range."} {"id": "PMID:1280007", "title": "A solid-phase assay for the activity of CMPNeuAc:Gal beta 1-4GlcNAc-R alpha-2,6-sialyltransferase.", "content": "A solid-phase assay for the activity of CMPNeuAc:Gal beta 1-4GlcNAc-R alpha-2,6-sialyltransferase (2,6ST) has been developed. In the assay an acceptor glycoprotein is immobilized onto microtiter plate wells. The two glycoprotein acceptors used were asialofetuin (ASF), which contains oligosaccharides terminating in the sequence Gal beta 1-4GlcNAc-R, and a neoglycoprotein of bovine serum albumin containing covalently attached Gal beta 1-4GlcNAc-R units. Samples containing the donor CMPNeuAc and the 2,6ST were incubated with the immobilized acceptor to generate the product NeuAc alpha 2-6Gal beta 1-4GlcNAc-R. The product was detected by a biotin-streptavidin system using the biotinylated plant lectin Sambucus nigra agglutinin (SNA), which binds to sialic acid in alpha-2,6, but not in alpha-2,3, linkage. The biotinylated SNA bound to the product was then detected with streptavidin and biotinylated forms of either alkaline phosphatase or the recombinant bioluminescent protein aequorin. The assay was optimized with respect to the commercially available 2,6ST and shown to be dependent on the concentration of acceptor and CMPNeuAc and proportional to the 2,6ST activity in the range of 20 to 400 microU in a 1-h assay. The solid-phase assay also allows for the selective detection of 2,6ST activity in human and fetal bovine serum, where the activity was proportional in the range of 0.1 to 2 microliters of serum.", "contents": "A solid-phase assay for the activity of CMPNeuAc:Gal beta 1-4GlcNAc-R alpha-2,6-sialyltransferase. A solid-phase assay for the activity of CMPNeuAc:Gal beta 1-4GlcNAc-R alpha-2,6-sialyltransferase (2,6ST) has been developed. In the assay an acceptor glycoprotein is immobilized onto microtiter plate wells. The two glycoprotein acceptors used were asialofetuin (ASF), which contains oligosaccharides terminating in the sequence Gal beta 1-4GlcNAc-R, and a neoglycoprotein of bovine serum albumin containing covalently attached Gal beta 1-4GlcNAc-R units. Samples containing the donor CMPNeuAc and the 2,6ST were incubated with the immobilized acceptor to generate the product NeuAc alpha 2-6Gal beta 1-4GlcNAc-R. The product was detected by a biotin-streptavidin system using the biotinylated plant lectin Sambucus nigra agglutinin (SNA), which binds to sialic acid in alpha-2,6, but not in alpha-2,3, linkage. The biotinylated SNA bound to the product was then detected with streptavidin and biotinylated forms of either alkaline phosphatase or the recombinant bioluminescent protein aequorin. The assay was optimized with respect to the commercially available 2,6ST and shown to be dependent on the concentration of acceptor and CMPNeuAc and proportional to the 2,6ST activity in the range of 20 to 400 microU in a 1-h assay. The solid-phase assay also allows for the selective detection of 2,6ST activity in human and fetal bovine serum, where the activity was proportional in the range of 0.1 to 2 microliters of serum."} {"id": "PMID:1280008", "title": "[A lectin histochemical study of the epidermis off the skin and the hoof of horses].", "content": "Carbohydrate moieties of cell membranes in the epidermis of equine skin and hoof were investigated using lectin-histochemistry. The loss of desmosomes during keratinization leads to a reduced lectin affinity. Lectin binding capacity of the intercellular matrix in the stratum corneum of the epidermis is weak compared to that of the intercellular kitt of the hoof. Qualitative differences in lectin binding of the intercellular kitt of different hoof segments correlate with the quality of the horn in the respective areas.", "contents": "[A lectin histochemical study of the epidermis off the skin and the hoof of horses]. Carbohydrate moieties of cell membranes in the epidermis of equine skin and hoof were investigated using lectin-histochemistry. The loss of desmosomes during keratinization leads to a reduced lectin affinity. Lectin binding capacity of the intercellular matrix in the stratum corneum of the epidermis is weak compared to that of the intercellular kitt of the hoof. Qualitative differences in lectin binding of the intercellular kitt of different hoof segments correlate with the quality of the horn in the respective areas."} {"id": "PMID:1280009", "title": "An anterograde tracing study of the vagal innervation of rat liver, portal vein and biliary system.", "content": "In order to investigate the distribution and structure of the vagal liver innervation, abdominal vagal afferents and efferents were selectively labeled by injecting WGA-HRP or Dil into the nodose ganglia, and DiA into the dorsal motor nucleus, respectively. Vagal afferent fibers produced characteristic terminal-like structures at three locations in the liver hilus: 1. Fine varicose endings preferentially surrounding, but not entering, the numerous peribiliary glands in the larger intra and extrahepatic bile ducts 2. Large, cup-shaped terminals in almost all paraganglia 3. Fine varicose endings in the portal vein adventitia. No fibers and terminals were found in the hepatic parenchyma. While about two thirds of the vagal afferent fibers that originate in the left nodose ganglion, and are contained in the hepatic branch, bypass the liver hilus area on their way to the gastroduodenal artery, a significant number (approx. 10% of the total) of vagal afferents that do innervate the area, originates from the right nodose ganglion, and projects to the periarterial plexus of the common hepatic artery and liver pedicle most likely through the dorsal celiac branch. Varicose vagal efferent fibers were present within the fascicles of the vagal hepatic branch and fine terminal-like structures in a small fraction of the paraganglia. No efferents were found to terminate in the hepatic parenchyma or on the few neurons embedded in nerves or paraganglia. In contrast to the paucity of vagal terminals in the hepatic parenchyma, an abundance of vagal efferent and afferent fibers and terminals with distinctive distribution patterns and structural characteristics was present in esophagus and gastrointestinal tract.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "An anterograde tracing study of the vagal innervation of rat liver, portal vein and biliary system. In order to investigate the distribution and structure of the vagal liver innervation, abdominal vagal afferents and efferents were selectively labeled by injecting WGA-HRP or Dil into the nodose ganglia, and DiA into the dorsal motor nucleus, respectively. Vagal afferent fibers produced characteristic terminal-like structures at three locations in the liver hilus: 1. Fine varicose endings preferentially surrounding, but not entering, the numerous peribiliary glands in the larger intra and extrahepatic bile ducts 2. Large, cup-shaped terminals in almost all paraganglia 3. Fine varicose endings in the portal vein adventitia. No fibers and terminals were found in the hepatic parenchyma. While about two thirds of the vagal afferent fibers that originate in the left nodose ganglion, and are contained in the hepatic branch, bypass the liver hilus area on their way to the gastroduodenal artery, a significant number (approx. 10% of the total) of vagal afferents that do innervate the area, originates from the right nodose ganglion, and projects to the periarterial plexus of the common hepatic artery and liver pedicle most likely through the dorsal celiac branch. Varicose vagal efferent fibers were present within the fascicles of the vagal hepatic branch and fine terminal-like structures in a small fraction of the paraganglia. No efferents were found to terminate in the hepatic parenchyma or on the few neurons embedded in nerves or paraganglia. In contrast to the paucity of vagal terminals in the hepatic parenchyma, an abundance of vagal efferent and afferent fibers and terminals with distinctive distribution patterns and structural characteristics was present in esophagus and gastrointestinal tract.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280010", "title": "Origin and fate of fetuin-containing neurons in the developing neocortex of the fetal sheep.", "content": "The development of the neocortex has previously been extensively studied in carnivores (cat and ferret), rodents (rat and mouse) and primates (monkey and human). In these species, it has been shown that the initial population of cells migrating from the ventricular zone forms the primordial plexiform layer. This is subsequently split into marginal zone and subplate zone by the insertion of later-migrating cells into the primordial plexiform layer, to form the cortical plate proper. Many of the cells derived from the split primordial plexiform layer are transient. The neurons of the subplate zone are found in the deeper part of layer VI, and white matter deep to layer VI in the more mature cortex; most of these neurons disappear by adulthood. [3H]-thymidine labelling in the present study has shown a similar pattern of neocortical development in Artiodactyla (sheep). In addition it has been shown that the previously described staining of subplate and cortical plate cells for the fetal protein fetuin indicates that fetuin is a useful marker for a proportion of this transient population of neurons and defines its extent in neocortical development more clearly. Dividing cells were labelled by a single intra-amniotic injection of [3H]-thymidine at E26 to E35 (birth is at E150). The brains were subsequently examined at E40 or E80 for [3H]-thymidine labelling and fetuin staining by a combination of autoradiography and immunocytochemistry. The earliest generated neocortical cells detected in this study (E26) were found in two layers by E40, the outer marginal zone and inner subplate zone. Neurons of the marginal zone were generated up to E28; those of the early subplate zone were generated up to E31. The cortical plate proper was generated by cells \"born\" on E32 and later. This sequence is similar to that described in other species, especially the cat. A proportion of the early-generated neurons in the marginal zone, subplate zone and early cortical plate stained for fetuin. By E80 these earliest-generated, fetuin-positive cells were found in the white matter deep to the forming neocortical layers and in layer VI. In adult brains no fetuin-positive neurons could be identified in the neocortex, and neurons had almost entirely disappeared from the white matter. The fetal glycoprotein fetuin seems to be specifically associated with a population of cells that has the same developmental history as the transient marginal zone and subplate neurons described in other species.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Origin and fate of fetuin-containing neurons in the developing neocortex of the fetal sheep. The development of the neocortex has previously been extensively studied in carnivores (cat and ferret), rodents (rat and mouse) and primates (monkey and human). In these species, it has been shown that the initial population of cells migrating from the ventricular zone forms the primordial plexiform layer. This is subsequently split into marginal zone and subplate zone by the insertion of later-migrating cells into the primordial plexiform layer, to form the cortical plate proper. Many of the cells derived from the split primordial plexiform layer are transient. The neurons of the subplate zone are found in the deeper part of layer VI, and white matter deep to layer VI in the more mature cortex; most of these neurons disappear by adulthood. [3H]-thymidine labelling in the present study has shown a similar pattern of neocortical development in Artiodactyla (sheep). In addition it has been shown that the previously described staining of subplate and cortical plate cells for the fetal protein fetuin indicates that fetuin is a useful marker for a proportion of this transient population of neurons and defines its extent in neocortical development more clearly. Dividing cells were labelled by a single intra-amniotic injection of [3H]-thymidine at E26 to E35 (birth is at E150). The brains were subsequently examined at E40 or E80 for [3H]-thymidine labelling and fetuin staining by a combination of autoradiography and immunocytochemistry. The earliest generated neocortical cells detected in this study (E26) were found in two layers by E40, the outer marginal zone and inner subplate zone. Neurons of the marginal zone were generated up to E28; those of the early subplate zone were generated up to E31. The cortical plate proper was generated by cells \"born\" on E32 and later. This sequence is similar to that described in other species, especially the cat. A proportion of the early-generated neurons in the marginal zone, subplate zone and early cortical plate stained for fetuin. By E80 these earliest-generated, fetuin-positive cells were found in the white matter deep to the forming neocortical layers and in layer VI. In adult brains no fetuin-positive neurons could be identified in the neocortex, and neurons had almost entirely disappeared from the white matter. The fetal glycoprotein fetuin seems to be specifically associated with a population of cells that has the same developmental history as the transient marginal zone and subplate neurons described in other species.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1280011", "title": "Keratin and vimentin distribution patterns in the epithelial structures of the canine anal region.", "content": "The intermediate filament labeling pattern of the epithelial structures of the canine anal region was studied with different polypeptide specific keratin monoclonal antibodies (MoAbs) and with a monoclonal and polyclonal vimentin antibody. The epithelial structures in this region could be discriminated and characterized by differences in their keratin staining pattern. The basal cells in the different epithelial structures showed a similar staining pattern characterized by reactivity with MoAbs staining keratins 5, 8, 14, and 17. Columnar epithelial cells showed a completely different phenotype mostly characterized by reactivity with MoAbs staining keratins 7, 5, 8, 18, and 19. A restricted number of differentiated perianal gland cells showed perinuclear vimentin staining. Myoepithelial cells did not stain for vimentin, but, as other basal cells, were positive for MoAbs staining keratins 5, 8, 14, and 17.", "contents": "Keratin and vimentin distribution patterns in the epithelial structures of the canine anal region. The intermediate filament labeling pattern of the epithelial structures of the canine anal region was studied with different polypeptide specific keratin monoclonal antibodies (MoAbs) and with a monoclonal and polyclonal vimentin antibody. The epithelial structures in this region could be discriminated and characterized by differences in their keratin staining pattern. The basal cells in the different epithelial structures showed a similar staining pattern characterized by reactivity with MoAbs staining keratins 5, 8, 14, and 17. Columnar epithelial cells showed a completely different phenotype mostly characterized by reactivity with MoAbs staining keratins 7, 5, 8, 18, and 19. A restricted number of differentiated perianal gland cells showed perinuclear vimentin staining. Myoepithelial cells did not stain for vimentin, but, as other basal cells, were positive for MoAbs staining keratins 5, 8, 14, and 17."} {"id": "PMID:1280013", "title": "Ethanol monitoring of transurethral prostatic resection during inhaled anesthesia.", "content": "The purpose of this study was to examine the precision of a method of breath-alcohol analysis used to monitor absorption of irrigating fluid during transurethral resection of the prostate performed under inhaled anesthesia. A breath-alcohol analyzer (Alcolmeter SD-2) was placed between the endotracheal tube and the Bains' circuit. The concentration of ethanol in the breath, serum sodium concentration, and volumetric fluid balance were measured at 10-min intervals during 38 operations when the irrigating fluid contained 1.5% glycine and 1% ethanol. Ethanol monitoring detected absorption rates that exceeded 14 +/- 8 mL/min (mean +/- SD). In 17 patients in whom hyponatremia developed immediately in connection with absorption, the volume of irrigating fluid absorbed (up to 1950 mL) could be predicted from a single expired-breath test with a standard error of 325 mL. When the alcohol measurements were corrected for absorption time, the standard error was 215 mL. Seven other patients received 2.2% wt/vol glycine as irrigating fluid, and ethanol (0.35 g/kg) was administered by intravenous infusion. The direct and indirect measurements of the blood-alcohol concentration agreed well. These results confirm that ethanol monitoring is a viable technique during inhaled anesthesia for transurethral resection of the prostate.", "contents": "Ethanol monitoring of transurethral prostatic resection during inhaled anesthesia. The purpose of this study was to examine the precision of a method of breath-alcohol analysis used to monitor absorption of irrigating fluid during transurethral resection of the prostate performed under inhaled anesthesia. A breath-alcohol analyzer (Alcolmeter SD-2) was placed between the endotracheal tube and the Bains' circuit. The concentration of ethanol in the breath, serum sodium concentration, and volumetric fluid balance were measured at 10-min intervals during 38 operations when the irrigating fluid contained 1.5% glycine and 1% ethanol. Ethanol monitoring detected absorption rates that exceeded 14 +/- 8 mL/min (mean +/- SD). In 17 patients in whom hyponatremia developed immediately in connection with absorption, the volume of irrigating fluid absorbed (up to 1950 mL) could be predicted from a single expired-breath test with a standard error of 325 mL. When the alcohol measurements were corrected for absorption time, the standard error was 215 mL. Seven other patients received 2.2% wt/vol glycine as irrigating fluid, and ethanol (0.35 g/kg) was administered by intravenous infusion. The direct and indirect measurements of the blood-alcohol concentration agreed well. These results confirm that ethanol monitoring is a viable technique during inhaled anesthesia for transurethral resection of the prostate."} {"id": "PMID:1280014", "title": "Human basophil/mast cell releasability. IX. Heterogeneity of the effects of opioids on mediator release.", "content": "Opioids differ in their capacity to cause release of histamine. The effects of increasing concentrations of three opioids (morphine, buprenorphine, and fentanyl) were studied on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2 [PGD2] and peptide-leukotriene C4 [LTC4]) chemical mediators from human peripheral blood basophils and mast cells isolated from skin tissues or lung parenchyma. Basophils released < 5% of their histamine content and did not synthesize significant amounts of LTC4 when incubated with any of the opioids. Mast cells showed markedly different responses to the three opioids. Morphine (10(-5)-3 x 10(-4) M), in a concentration-dependent manner, induced histamine and tryptase release from skin but not from lung mast cells, up to a maximum of 18.2 +/- 1.9% and 13.0 +/- 4.1 micrograms/10(7) cells, respectively. Morphine did not induce de novo synthesis of PGD2 from skin mast cells. Buprenorphine (10(-6)-10(-4) M), in a concentration-dependent manner, caused histamine and tryptase release from lung but not from skin mast cells, to a maximum of 47.6 +/- 7.2% and 35.1 +/- 13.6 micrograms/10(7) cells, respectively. Buprenorphine also induced de novo synthesis of PGD2 and LTC4 from lung mast cells. Fentanyl (10(-5)-10(-3) M) did not induce histamine and tryptase release or the de novo synthesis of PGD2 or LTC4 from any mast cells. Histamine release caused by buprenorphine from lung mast cells was slow (t1/2 = 11.2 +/- 3.6 min) compared with that induced by morphine from skin mast cells (t1/2 < 1 min, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Human basophil/mast cell releasability. IX. Heterogeneity of the effects of opioids on mediator release. Opioids differ in their capacity to cause release of histamine. The effects of increasing concentrations of three opioids (morphine, buprenorphine, and fentanyl) were studied on the release of preformed (histamine and tryptase) and de novo synthesized (prostaglandin D2 [PGD2] and peptide-leukotriene C4 [LTC4]) chemical mediators from human peripheral blood basophils and mast cells isolated from skin tissues or lung parenchyma. Basophils released < 5% of their histamine content and did not synthesize significant amounts of LTC4 when incubated with any of the opioids. Mast cells showed markedly different responses to the three opioids. Morphine (10(-5)-3 x 10(-4) M), in a concentration-dependent manner, induced histamine and tryptase release from skin but not from lung mast cells, up to a maximum of 18.2 +/- 1.9% and 13.0 +/- 4.1 micrograms/10(7) cells, respectively. Morphine did not induce de novo synthesis of PGD2 from skin mast cells. Buprenorphine (10(-6)-10(-4) M), in a concentration-dependent manner, caused histamine and tryptase release from lung but not from skin mast cells, to a maximum of 47.6 +/- 7.2% and 35.1 +/- 13.6 micrograms/10(7) cells, respectively. Buprenorphine also induced de novo synthesis of PGD2 and LTC4 from lung mast cells. Fentanyl (10(-5)-10(-3) M) did not induce histamine and tryptase release or the de novo synthesis of PGD2 or LTC4 from any mast cells. Histamine release caused by buprenorphine from lung mast cells was slow (t1/2 = 11.2 +/- 3.6 min) compared with that induced by morphine from skin mast cells (t1/2 < 1 min, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280012", "title": "Sperm plasma membrane integrity measurement: a combined method.", "content": "Sperm plasma membrane characteristics were measured by a combined method consisting of the hypo-osmotic swelling test and staining with either the eosine Y (HOS-eosine test) or propidium iodide dye (HOS-propidium test). Sperm samples were washed and resuspended in BWW medium (fraction I). Aliquots of the washed spermatozoa were treated by a swim-up technique to select motile spermatozoa (fraction II). After separation of motile cells, residual sperm pellets were treated separately (fraction III). These three fractions were subjected to the hypo-osmotic swelling test, lipid peroxidation measurement, and the HOS-eosine and HOS-propidium tests. The HOS-eosine test makes it possible to distinguish 4 types of spermatozoa: type 1: HOS+/eosine-; type 2: HOS-/eosine-; type 3: HOS-/eosine+ and type 4: HOS+/eosine+ (Fig. 1). HOS-propidium test shows equal results as HOS-eosine test. Fraction I spermatozoa showed 55.2 +/- 3.6% type 1; 12.6 +/- 1.0 type 2; 28.0 +/- 2.9 type 3; and 4.2 +/- 0.6 type 4 cells. Fraction II spermatozoa were characterized by high percentages of type 1 cells, low percentages of types 3 and 4, and very low values of lipid peroxidation (5 times smaller than fraction I). Fraction III showed a low percentage of type 1, a high percentages of the other types, and an enhanced value of lipid peroxidation (2 times higher than fraction I). The prognostic value of the HOS-eosine test was evaluated in an IVF programme. Preliminary results show that a high incidence of types 2 and 4 spermatozoa is often associated with fertilization failure.", "contents": "Sperm plasma membrane integrity measurement: a combined method. Sperm plasma membrane characteristics were measured by a combined method consisting of the hypo-osmotic swelling test and staining with either the eosine Y (HOS-eosine test) or propidium iodide dye (HOS-propidium test). Sperm samples were washed and resuspended in BWW medium (fraction I). Aliquots of the washed spermatozoa were treated by a swim-up technique to select motile spermatozoa (fraction II). After separation of motile cells, residual sperm pellets were treated separately (fraction III). These three fractions were subjected to the hypo-osmotic swelling test, lipid peroxidation measurement, and the HOS-eosine and HOS-propidium tests. The HOS-eosine test makes it possible to distinguish 4 types of spermatozoa: type 1: HOS+/eosine-; type 2: HOS-/eosine-; type 3: HOS-/eosine+ and type 4: HOS+/eosine+ (Fig. 1). HOS-propidium test shows equal results as HOS-eosine test. Fraction I spermatozoa showed 55.2 +/- 3.6% type 1; 12.6 +/- 1.0 type 2; 28.0 +/- 2.9 type 3; and 4.2 +/- 0.6 type 4 cells. Fraction II spermatozoa were characterized by high percentages of type 1 cells, low percentages of types 3 and 4, and very low values of lipid peroxidation (5 times smaller than fraction I). Fraction III showed a low percentage of type 1, a high percentages of the other types, and an enhanced value of lipid peroxidation (2 times higher than fraction I). The prognostic value of the HOS-eosine test was evaluated in an IVF programme. Preliminary results show that a high incidence of types 2 and 4 spermatozoa is often associated with fertilization failure."} {"id": "PMID:1280016", "title": "One-dimensional isoelectric focusing and immunoblotting of equine major histocompatibility complex class I antigens.", "content": "The cells of 60 randomly selected Hannoveranian warm-blooded horses were subjected to one-dimensional isoelectric focusing and immunoblotting with a cross-reacting monoclonal antibody (Bo 1) recognizing bovine class I antigens. The banding patterns were correlated with the serologically defined specificities of the ELA-A locus. ELA-A2 was correlated with four bands, while ELA-A5, ELA-W18, ELA-A6, ELA-A14 and ELA-A9 were correlated with a single band each. The complexity of the pattern and additional polymorphic bands which could not be correlated to any of the known ELA specificities may indicate biochemical variants of established serological specificities or still-undetected allelic products of more than one class I locus expressed at the surface of horse cells. Here we present the first description of the biochemical complex polymorphism of equine MHC class I molecules using one-dimensional isoelectric focusing. Direct comparison of biochemical and serological polymorphisms revealed potentials and limitations of both techniques which supplement each other. Their combination will improve and enhance the definition of expressed products of different loci in the ELA class I region.", "contents": "One-dimensional isoelectric focusing and immunoblotting of equine major histocompatibility complex class I antigens. The cells of 60 randomly selected Hannoveranian warm-blooded horses were subjected to one-dimensional isoelectric focusing and immunoblotting with a cross-reacting monoclonal antibody (Bo 1) recognizing bovine class I antigens. The banding patterns were correlated with the serologically defined specificities of the ELA-A locus. ELA-A2 was correlated with four bands, while ELA-A5, ELA-W18, ELA-A6, ELA-A14 and ELA-A9 were correlated with a single band each. The complexity of the pattern and additional polymorphic bands which could not be correlated to any of the known ELA specificities may indicate biochemical variants of established serological specificities or still-undetected allelic products of more than one class I locus expressed at the surface of horse cells. Here we present the first description of the biochemical complex polymorphism of equine MHC class I molecules using one-dimensional isoelectric focusing. Direct comparison of biochemical and serological polymorphisms revealed potentials and limitations of both techniques which supplement each other. Their combination will improve and enhance the definition of expressed products of different loci in the ELA class I region."} {"id": "PMID:1280018", "title": "Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham Heart Study.", "content": "To evaluate the prevalence and prognostic significance of asymptomatic complex or frequent ventricular premature beats detected during ambulatory electrocardiographic (ECG) monitoring. Cohort study with a follow-up period of 4 to 6 years. Population-based. Surviving patients of the original Framingham Heart Study cohort and offspring of original cohort members (2727 men and 3306 women). One-hour ambulatory electrocardiography. The age-adjusted prevalence of complex or frequent arrhythmia (more than 30 ventricular premature complexes per hour or multiform premature complexes, ventricular couplets, ventricular tachycardia, or R-on-T ventricular premature complexes) was 12% (95% Cl, 11% to 13%) in the 2425 men without clinically evident coronary heart disease and 33% (Cl, 24% to 42%) in the 302 men with coronary heart disease. The corresponding values in women (3064 without disease and 242 with disease) were 12% (Cl, 11% to 13%) and 26% (Cl, 9% to 43%). After adjusting for age and traditional risk factors for coronary heart disease in a Cox proportional hazards model, men without coronary heart disease who had complex or frequent ventricular arrhythmias were at increased risk for both all-cause mortality (relative risk, 2.30; Cl, 1.65 to 3.20) and the occurrence of myocardial infarction or death from coronary heart disease (relative risk, 2.12; Cl, 1.33 to 3.38). In men with coronary heart disease and in women with and without coronary heart disease, complex or frequent arrhythmias were not associated with an increased risk for either outcome. In men who do not have clinically apparent coronary heart disease, the incidental detection of ventricular arrhythmias is associated with a twofold increase in the risk for all-cause mortality and myocardial infarction or death due to coronary heart disease. The preventive and therapeutic implications of these findings await further investigation.", "contents": "Prognostic implications of asymptomatic ventricular arrhythmias: the Framingham Heart Study. To evaluate the prevalence and prognostic significance of asymptomatic complex or frequent ventricular premature beats detected during ambulatory electrocardiographic (ECG) monitoring. Cohort study with a follow-up period of 4 to 6 years. Population-based. Surviving patients of the original Framingham Heart Study cohort and offspring of original cohort members (2727 men and 3306 women). One-hour ambulatory electrocardiography. The age-adjusted prevalence of complex or frequent arrhythmia (more than 30 ventricular premature complexes per hour or multiform premature complexes, ventricular couplets, ventricular tachycardia, or R-on-T ventricular premature complexes) was 12% (95% Cl, 11% to 13%) in the 2425 men without clinically evident coronary heart disease and 33% (Cl, 24% to 42%) in the 302 men with coronary heart disease. The corresponding values in women (3064 without disease and 242 with disease) were 12% (Cl, 11% to 13%) and 26% (Cl, 9% to 43%). After adjusting for age and traditional risk factors for coronary heart disease in a Cox proportional hazards model, men without coronary heart disease who had complex or frequent ventricular arrhythmias were at increased risk for both all-cause mortality (relative risk, 2.30; Cl, 1.65 to 3.20) and the occurrence of myocardial infarction or death from coronary heart disease (relative risk, 2.12; Cl, 1.33 to 3.38). In men with coronary heart disease and in women with and without coronary heart disease, complex or frequent arrhythmias were not associated with an increased risk for either outcome. In men who do not have clinically apparent coronary heart disease, the incidental detection of ventricular arrhythmias is associated with a twofold increase in the risk for all-cause mortality and myocardial infarction or death due to coronary heart disease. The preventive and therapeutic implications of these findings await further investigation."} {"id": "PMID:1280020", "title": "Immunohistochemical analysis of the cytokeratin expression in middle ear cholesteatoma and related epithelial tissues.", "content": "Immunohistochemical investigations were carried out to determine the pattern of cytokeratin (CK) expression in middle ear cholesteatoma and related epithelia. Using monoclonal antibodies specific for CK chains and the indirect immunoperoxidase technique, we examined 10 CK polypeptides for expression. The external stratified squamous epithelium of the tympanic membrane generally expressed CKs 5, 10, and 14. In addition, basal keratinocytes in the annular region of the pars tensa expressed CK 19 (a simple epithelium marker), while suprabasally the hyperproliferative marker CK 16 was expressed. These data reflect the unusual proliferative nature of this region. The unexpected appearance of CK 16 (known to have a limited distribution in healthy epidermis) clearly relates to its expression in the neighboring deep meatus. The medial simple epithelium of the eardrum revealed mucosal CKs 7, 8, 14, 18, and 19. Acquired cholesteatoma lesions, besides CKs 5, 10, and 14, consistently expressed CK 16 in suprabasal layers. These results constitute the first direct molecular evidence for the hyperproliferative nature of the cholesteatoma matrix. Overall, our CK data suggest that aural cholesteatoma lesions and epidermal tissue in this area are related. However, they do not explain the mechanism(s) by which the eardrum or meatal epithelia might invade the middle ear cavity. Congenital cholesteatomas expressed CKs 5, 10, 14, and 16 equally. These CK data do not support the idea of a metaplastic origin from middle ear mucosa; instead, they suggest activation of an ectodermal rest in the middle ear cavity.", "contents": "Immunohistochemical analysis of the cytokeratin expression in middle ear cholesteatoma and related epithelial tissues. Immunohistochemical investigations were carried out to determine the pattern of cytokeratin (CK) expression in middle ear cholesteatoma and related epithelia. Using monoclonal antibodies specific for CK chains and the indirect immunoperoxidase technique, we examined 10 CK polypeptides for expression. The external stratified squamous epithelium of the tympanic membrane generally expressed CKs 5, 10, and 14. In addition, basal keratinocytes in the annular region of the pars tensa expressed CK 19 (a simple epithelium marker), while suprabasally the hyperproliferative marker CK 16 was expressed. These data reflect the unusual proliferative nature of this region. The unexpected appearance of CK 16 (known to have a limited distribution in healthy epidermis) clearly relates to its expression in the neighboring deep meatus. The medial simple epithelium of the eardrum revealed mucosal CKs 7, 8, 14, 18, and 19. Acquired cholesteatoma lesions, besides CKs 5, 10, and 14, consistently expressed CK 16 in suprabasal layers. These results constitute the first direct molecular evidence for the hyperproliferative nature of the cholesteatoma matrix. Overall, our CK data suggest that aural cholesteatoma lesions and epidermal tissue in this area are related. However, they do not explain the mechanism(s) by which the eardrum or meatal epithelia might invade the middle ear cavity. Congenital cholesteatomas expressed CKs 5, 10, 14, and 16 equally. These CK data do not support the idea of a metaplastic origin from middle ear mucosa; instead, they suggest activation of an ectodermal rest in the middle ear cavity."} {"id": "PMID:1280025", "title": "Glycated haemoglobin: an assessment of high capacity liquid chromatographic and immunoassay methods.", "content": "We have assessed five high-throughput systems for the measurement of glycated haemoglobin and have reviewed published evaluations of individual analysers. All systems offered better precision than a widely used electroendosmosis method. The low pressure chromatography and immunoassay systems demonstrated greater between-batch imprecision than the high performance liquid chromatography analysers, the latter achieving the proposed analytical goal of between-batch coefficients of variation less than 5%. Agreement between all systems measuring HbA1 was good but there was variability amongst observed HbA1c values. The systems were also assessed for their quality of chromatographic separation, simplicity of operation, flexibility, cost and potential for interference by other haemoglobins.", "contents": "Glycated haemoglobin: an assessment of high capacity liquid chromatographic and immunoassay methods. We have assessed five high-throughput systems for the measurement of glycated haemoglobin and have reviewed published evaluations of individual analysers. All systems offered better precision than a widely used electroendosmosis method. The low pressure chromatography and immunoassay systems demonstrated greater between-batch imprecision than the high performance liquid chromatography analysers, the latter achieving the proposed analytical goal of between-batch coefficients of variation less than 5%. Agreement between all systems measuring HbA1 was good but there was variability amongst observed HbA1c values. The systems were also assessed for their quality of chromatographic separation, simplicity of operation, flexibility, cost and potential for interference by other haemoglobins."} {"id": "PMID:1280026", "title": "Free beta human choriogonadotropin in Down's syndrome screening: a multicentre study of its role compared with other biochemical markers.", "content": "To ascertain the value of maternal serum free beta-human choriogonadotropin subunit measurement in Down's syndrome screening and to compare its effectiveness when screening with a variety of biochemical markers, we have evaluated maternal serum free beta-human choriogonadotropin, total human choriogonadotropin, alpha-fetoprotein and unconjugated oestriol in a large multicentre study of over 2800 unaffected cases and 90 affected cases, the largest collection of Down's cases ever reported. Of all the markers identified to date, free beta-human choriogonadotropin is the marker of choice for use in Down's syndrome screening. When used in early gestation (14-16 weeks) in combination with alpha-fetoprotein and maternal age, it will allow the detection of 77% of Down's cases. A side-by-side comparison with the performance of total human choriogonadotropin shows the superior detection efficiency of free beta-human choriogonadotropin. Unconjugated oestriol adds nothing further to the detection rate compared with the use of alpha-fetoprotein and free beta-human choriogonadotropin alone, and its use results in a 1% increase in false positive rate. We conclude that unconjugated oestriol has no value in Down's screening. The superior detection rate obtained using free beta-human choriogonadotropin is a result of superior detection of Down's cases in women under 30 years old, where the free beta-human choriogonadotropin combination detects 100% more cases than does the total human choriogonadotropin combination.", "contents": "Free beta human choriogonadotropin in Down's syndrome screening: a multicentre study of its role compared with other biochemical markers. To ascertain the value of maternal serum free beta-human choriogonadotropin subunit measurement in Down's syndrome screening and to compare its effectiveness when screening with a variety of biochemical markers, we have evaluated maternal serum free beta-human choriogonadotropin, total human choriogonadotropin, alpha-fetoprotein and unconjugated oestriol in a large multicentre study of over 2800 unaffected cases and 90 affected cases, the largest collection of Down's cases ever reported. Of all the markers identified to date, free beta-human choriogonadotropin is the marker of choice for use in Down's syndrome screening. When used in early gestation (14-16 weeks) in combination with alpha-fetoprotein and maternal age, it will allow the detection of 77% of Down's cases. A side-by-side comparison with the performance of total human choriogonadotropin shows the superior detection efficiency of free beta-human choriogonadotropin. Unconjugated oestriol adds nothing further to the detection rate compared with the use of alpha-fetoprotein and free beta-human choriogonadotropin alone, and its use results in a 1% increase in false positive rate. We conclude that unconjugated oestriol has no value in Down's screening. The superior detection rate obtained using free beta-human choriogonadotropin is a result of superior detection of Down's cases in women under 30 years old, where the free beta-human choriogonadotropin combination detects 100% more cases than does the total human choriogonadotropin combination."} {"id": "PMID:1280027", "title": "Highly sensitive sandwich enzyme immunoassay for alpha-fetoprotein in human saliva.", "content": "To determine alpha-fetoprotein (AFP) in human saliva, a highly sensitive sandwich enzyme immunoassay for saliva AFP was developed. AFP standards and saliva samples were added into the wells of a polystyrene plate coated with goat IgG antibody against human AFP. After incubation, the wells were washed and horseradish peroxidase-labelled antibody was added. The enzyme activity specifically bound to the well was assayed using 3,3',5,5'-tetramethylbenzidine and hydrogen peroxide as substrate. The reaction was stopped by addition of 2 M sulphuric acid and the AFP concentration was determined from the absorbance at 450 nm. The minimum detectable concentration was 8 ng/L. The recovery of AFP mixed with human saliva was 91.1-102.4%. The within-assay and between-assay coefficients of variation were 6.5-8.9% and 7.6-10.8%, respectively. The assay correlated well with a radioimmunoassay for human AFP (r = 0.985, n = 13, P less than 0.001). The mean concentration of AFP in normal human saliva was 14.3 ng/L (SEM = 4.9 ng/L, n = 10) and significantly higher levels of saliva AFP were observed in hepatocellular carcinoma patients with positive serum AFP (mean 1367.8 ng/L, SEM 595.4 ng/L, n = 6; P less than 0.001). Strong correlation was observed between saliva AFP and serum AFP (r = 0.978, P less than 0.01, n = 13).", "contents": "Highly sensitive sandwich enzyme immunoassay for alpha-fetoprotein in human saliva. To determine alpha-fetoprotein (AFP) in human saliva, a highly sensitive sandwich enzyme immunoassay for saliva AFP was developed. AFP standards and saliva samples were added into the wells of a polystyrene plate coated with goat IgG antibody against human AFP. After incubation, the wells were washed and horseradish peroxidase-labelled antibody was added. The enzyme activity specifically bound to the well was assayed using 3,3',5,5'-tetramethylbenzidine and hydrogen peroxide as substrate. The reaction was stopped by addition of 2 M sulphuric acid and the AFP concentration was determined from the absorbance at 450 nm. The minimum detectable concentration was 8 ng/L. The recovery of AFP mixed with human saliva was 91.1-102.4%. The within-assay and between-assay coefficients of variation were 6.5-8.9% and 7.6-10.8%, respectively. The assay correlated well with a radioimmunoassay for human AFP (r = 0.985, n = 13, P less than 0.001). The mean concentration of AFP in normal human saliva was 14.3 ng/L (SEM = 4.9 ng/L, n = 10) and significantly higher levels of saliva AFP were observed in hepatocellular carcinoma patients with positive serum AFP (mean 1367.8 ng/L, SEM 595.4 ng/L, n = 6; P less than 0.001). Strong correlation was observed between saliva AFP and serum AFP (r = 0.978, P less than 0.01, n = 13)."} {"id": "PMID:1280028", "title": "[Treatment of aggressive primary lymphomas of the digestive system by intensive chemotherapy. Experience of the Study Group on Lymphomas in Adults with the LNH-84 protocol].", "content": "Ninety-one patients with primary gastrointestinal lymphoma included in the LNH-84 multicentric regimen were analyzed to determine the efficacy and the toxicity of intensive combination chemotherapy and of surgical debulking. All these patients had aggressive histological subtypes: 56 patients had localize disease, stage IE or IIE, and 35 patients had stage IV disease; 40 patients had bulky disease. Specific sites included stomach (43 cases), small bowel (35), ileo-cecum (13), colon (10), and rectum (6). Although 71 patients (78%) had an attempted surgical resection, only 28 (31%) had complete tumor excision. Patients were treated with 3 or 4 cycles of ACVB chemotherapy followed by sequential consolidation. Nine patients died during chemotherapy. With a median follow-up of 3 years, 10 patients have relapsed and predicted 4-year survival of the entire group is 62%. In stage IE or IIE patients, survival and disease-free survival are similar in patients who underwent complete resection or incomplete or no surgical resection prior to the administration of chemotherapy. Prognostic factors predicting for survival were similar to the entire group of patients treated with the LNH-84 regimen. Aggressive gastrointestinal lymphoma patients treated with intensive chemotherapy have outcome and prognostic factors comparable to those of other similarly staged aggressive lymphoma patients. Surgical resection prior to the administration of combination chemotherapy did not influence survival or disease-free survival in patients with localized disease.", "contents": "[Treatment of aggressive primary lymphomas of the digestive system by intensive chemotherapy. Experience of the Study Group on Lymphomas in Adults with the LNH-84 protocol]. Ninety-one patients with primary gastrointestinal lymphoma included in the LNH-84 multicentric regimen were analyzed to determine the efficacy and the toxicity of intensive combination chemotherapy and of surgical debulking. All these patients had aggressive histological subtypes: 56 patients had localize disease, stage IE or IIE, and 35 patients had stage IV disease; 40 patients had bulky disease. Specific sites included stomach (43 cases), small bowel (35), ileo-cecum (13), colon (10), and rectum (6). Although 71 patients (78%) had an attempted surgical resection, only 28 (31%) had complete tumor excision. Patients were treated with 3 or 4 cycles of ACVB chemotherapy followed by sequential consolidation. Nine patients died during chemotherapy. With a median follow-up of 3 years, 10 patients have relapsed and predicted 4-year survival of the entire group is 62%. In stage IE or IIE patients, survival and disease-free survival are similar in patients who underwent complete resection or incomplete or no surgical resection prior to the administration of chemotherapy. Prognostic factors predicting for survival were similar to the entire group of patients treated with the LNH-84 regimen. Aggressive gastrointestinal lymphoma patients treated with intensive chemotherapy have outcome and prognostic factors comparable to those of other similarly staged aggressive lymphoma patients. Surgical resection prior to the administration of combination chemotherapy did not influence survival or disease-free survival in patients with localized disease."} {"id": "PMID:1280029", "title": "Clastogenic interactions between lobeline sulfate and ethyl alcohol: a cytogenetic study.", "content": "The clastogenicity of lobeline and possible interactions between lobeline and ethyl alcohol were investigated in a mutagen-sensitivity assay on cultures of human lymphoblastoid cell lines. Lobeline (10(-6) M) and ethyl alcohol (1% and 2%) were added to the cultures alone or in different combinations prior to or simultaneously with bleomycin treatment. The number of chromatid breaks per cell served as the indicator of clastogenicity. Lobeline alone was not clastogenic, but there was a marked increase in genetic damage resulting from a coclastogenic interaction between lobeline and ethyl alcohol. These data emphasize the significance of interactions between compounds that may increase genotoxicity in cells exposed to mutagenic environments.", "contents": "Clastogenic interactions between lobeline sulfate and ethyl alcohol: a cytogenetic study. The clastogenicity of lobeline and possible interactions between lobeline and ethyl alcohol were investigated in a mutagen-sensitivity assay on cultures of human lymphoblastoid cell lines. Lobeline (10(-6) M) and ethyl alcohol (1% and 2%) were added to the cultures alone or in different combinations prior to or simultaneously with bleomycin treatment. The number of chromatid breaks per cell served as the indicator of clastogenicity. Lobeline alone was not clastogenic, but there was a marked increase in genetic damage resulting from a coclastogenic interaction between lobeline and ethyl alcohol. These data emphasize the significance of interactions between compounds that may increase genotoxicity in cells exposed to mutagenic environments."} {"id": "PMID:1280030", "title": "Enhancement of cytotoxicity by hyperthermia after a long-term culture with 5-fluorouracil in transformed cells.", "content": "The cytotoxic effect of 5-FU (5-fluorouracil) was demonstrated to be enhanced by hyperthermia after treatment with 5-FU at even a comparatively low dose over fairly long periods. The cytotoxic effect of the combined treatment with 42 degrees C-hyperthermia and 1 microgram/ml 5-FU for 48 hrs, the cytotoxic effect of 42 degrees C-hyperthermia and 5 micrograms/ml 5-FU for 24 hrs, and the cytotoxic effect of 43 degrees C-hyperthermia and 1 and 5 micrograms/ml 5-FU for 8 hrs were studied. The maximally enhanced rate of 42 degrees C-hyperthermia after 5-FU treatment for 96 hrs was 48% after a 1 microgram/ml 5-FU treatment and 150% after 45 hrs with the 5 micrograms/ml 5-FU treatment. The maximally enhanced rate of 43 degrees C-hyperthermia after 5-FU treatment was 170% after 45 hrs with 1 microgram/ml 5-FU treatment and 180% after 24 hrs with 5 mg/ml 5-FU treatment. When V-79 cells were treated at the same temperature, the maximally enhanced rate with 1 microgram/ml 5-FU was almost equal to that of 5 micrograms/ml. Moreover, when each maximally enhanced rate was equalized, each concentration of FU (RNA)/RNA practically became equal, i.e., when the maximally enhanced rates were approximately 150 and 170-180%, FU (RNA)/RNA concentrations were about 40 and 15 ng/mg RNA, respectively. We thus concluded that FU (RNA)/RNA concentration might play an important role as an indicator of the effect of the combined treatment of 5-FU and hyperthermia.", "contents": "Enhancement of cytotoxicity by hyperthermia after a long-term culture with 5-fluorouracil in transformed cells. The cytotoxic effect of 5-FU (5-fluorouracil) was demonstrated to be enhanced by hyperthermia after treatment with 5-FU at even a comparatively low dose over fairly long periods. The cytotoxic effect of the combined treatment with 42 degrees C-hyperthermia and 1 microgram/ml 5-FU for 48 hrs, the cytotoxic effect of 42 degrees C-hyperthermia and 5 micrograms/ml 5-FU for 24 hrs, and the cytotoxic effect of 43 degrees C-hyperthermia and 1 and 5 micrograms/ml 5-FU for 8 hrs were studied. The maximally enhanced rate of 42 degrees C-hyperthermia after 5-FU treatment for 96 hrs was 48% after a 1 microgram/ml 5-FU treatment and 150% after 45 hrs with the 5 micrograms/ml 5-FU treatment. The maximally enhanced rate of 43 degrees C-hyperthermia after 5-FU treatment was 170% after 45 hrs with 1 microgram/ml 5-FU treatment and 180% after 24 hrs with 5 mg/ml 5-FU treatment. When V-79 cells were treated at the same temperature, the maximally enhanced rate with 1 microgram/ml 5-FU was almost equal to that of 5 micrograms/ml. Moreover, when each maximally enhanced rate was equalized, each concentration of FU (RNA)/RNA practically became equal, i.e., when the maximally enhanced rates were approximately 150 and 170-180%, FU (RNA)/RNA concentrations were about 40 and 15 ng/mg RNA, respectively. We thus concluded that FU (RNA)/RNA concentration might play an important role as an indicator of the effect of the combined treatment of 5-FU and hyperthermia."} {"id": "PMID:1280031", "title": "Establishment and characterization of two new cell lines derived from squamous cell carcinoma of the tongue in Chinese patients.", "content": "Two new cell lines derived from squamous cell carcinoma of the tongue, T1/CUHK and T2/CUHK, have been established in culture. Analysis of the morphology, ultrastructure, chromosome number, spheroid formation and immunohistochemical properties of the two cell lines demonstrated that they are both well characterized. T1/CUHK cells grew relatively faster than T2/CUHK cells. Both cell lines were tumorigenic after inoculation into made mice and showed positive reactivity with HPV 16 DNA probe. The reactivity of both cell lines with HPV 18 DNA probe was weak.", "contents": "Establishment and characterization of two new cell lines derived from squamous cell carcinoma of the tongue in Chinese patients. Two new cell lines derived from squamous cell carcinoma of the tongue, T1/CUHK and T2/CUHK, have been established in culture. Analysis of the morphology, ultrastructure, chromosome number, spheroid formation and immunohistochemical properties of the two cell lines demonstrated that they are both well characterized. T1/CUHK cells grew relatively faster than T2/CUHK cells. Both cell lines were tumorigenic after inoculation into made mice and showed positive reactivity with HPV 16 DNA probe. The reactivity of both cell lines with HPV 18 DNA probe was weak."} {"id": "PMID:1280032", "title": "Inhibitory effects of dextran derivatives in vitro on the growth characteristics of premalignant and malignant human mammary epithelial cell lines.", "content": "The effects of two dextran derivatives (CMDBS-6 and CMDBS-12) on the growth rates of three human mammary epithelial cell lines (HBL100,HH9 and MCF7) were studied. CMDBS-6 markedly inhibited the growth of all lines, while CMDBS-12 and native dextran T40 had no effect on the growth of all lines. This inhibition was dose-dependent, reversible and inversely related to the concentration of fetal calf serum. The inhibitory effect of CMDBS-6 is cytostatic but not cytotoxic. Moreover, CMDBS-6 appears to have a stronger effect on HBL100 cells which are non-tumorigenic in nude mice. In contrast, the growth of HH9 cells, which are highly tumorigenic in nude mice, is less inhibited by CMDBS-6. Whereas CMDBS-6 inhibited the HBL100 cell anchorage, that of HH9 cells was not affected. By analysing the cell distribution in the various phases of the cell cycle, we have observed that CMDBS-6 arrested HBL100 and MCF7 cell mainly in the G0/GI phase. In contrast, HH9 cells were accumulated in the G2/M phase. When treated with CMDBS-6, human mammary cells slightly increased their granularities. These results demonstrate an antiproliferative activity of CMDBS-6 which could not be explained by an inactivation of mitogens provided by the serum but suggest that this compound could exert its cytostatic effects via a cell-specific mechanism.", "contents": "Inhibitory effects of dextran derivatives in vitro on the growth characteristics of premalignant and malignant human mammary epithelial cell lines. The effects of two dextran derivatives (CMDBS-6 and CMDBS-12) on the growth rates of three human mammary epithelial cell lines (HBL100,HH9 and MCF7) were studied. CMDBS-6 markedly inhibited the growth of all lines, while CMDBS-12 and native dextran T40 had no effect on the growth of all lines. This inhibition was dose-dependent, reversible and inversely related to the concentration of fetal calf serum. The inhibitory effect of CMDBS-6 is cytostatic but not cytotoxic. Moreover, CMDBS-6 appears to have a stronger effect on HBL100 cells which are non-tumorigenic in nude mice. In contrast, the growth of HH9 cells, which are highly tumorigenic in nude mice, is less inhibited by CMDBS-6. Whereas CMDBS-6 inhibited the HBL100 cell anchorage, that of HH9 cells was not affected. By analysing the cell distribution in the various phases of the cell cycle, we have observed that CMDBS-6 arrested HBL100 and MCF7 cell mainly in the G0/GI phase. In contrast, HH9 cells were accumulated in the G2/M phase. When treated with CMDBS-6, human mammary cells slightly increased their granularities. These results demonstrate an antiproliferative activity of CMDBS-6 which could not be explained by an inactivation of mitogens provided by the serum but suggest that this compound could exert its cytostatic effects via a cell-specific mechanism."} {"id": "PMID:1280035", "title": "Diethylene glycol poisoning in Nigerian children.", "content": "Between June and September 1990, 47 children died at Jos University Teaching Hospital, Nigeria from ingestion of paracetamol syrup adulterated with diethylene glycol. Most of the children presented with anuria, fever, vomiting, diarrhoea and convulsions. Signs on admission were tachycardia, acidotic breathing, pallor, oedema and hepatomegaly. Laboratory findings included hyperkalaemia, acidosis, elevated creatinine level and hypoglycaemia. Management consisted of correction of dehydration and acidosis plus administration of antibiotics when indicated. None of the children had dialysis. All died within 2 weeks of admission. Proper government supervision of pharmaceutical companies and their agencies is urgently needed in order to prevent any future occurrence of such tragic deaths.", "contents": "Diethylene glycol poisoning in Nigerian children. Between June and September 1990, 47 children died at Jos University Teaching Hospital, Nigeria from ingestion of paracetamol syrup adulterated with diethylene glycol. Most of the children presented with anuria, fever, vomiting, diarrhoea and convulsions. Signs on admission were tachycardia, acidotic breathing, pallor, oedema and hepatomegaly. Laboratory findings included hyperkalaemia, acidosis, elevated creatinine level and hypoglycaemia. Management consisted of correction of dehydration and acidosis plus administration of antibiotics when indicated. None of the children had dialysis. All died within 2 weeks of admission. Proper government supervision of pharmaceutical companies and their agencies is urgently needed in order to prevent any future occurrence of such tragic deaths."} {"id": "PMID:1280033", "title": "Expression of the gene coding for the light chain of calpactin I (annexin II) in cell lines DiFi, HT-29, and WI-38.", "content": "Calpactin I (annexin II) light chain gene messages were expressed in the DiFi and HT-29 human colon cancer cell lines, as well as in the diploid lung fibroblast cell line WI-38. However, expression of an approximately 1.0 kb transcript was stronger in DiFi and HT-29 cells than in WI-38 cells. The moderate to strong expression of such transcripts in DiFi and HT-29 cells indicates that the calcium binding protein, calpactin I, may be abundant in colon carcinoma cells. Calpactin I is the major substrate of pp60v-src, a tyrosine-specific protein kinase encoded by v-src, whose cellular homologue c-src also codes for a tyrosine kinase (pp60c-src), known to be activated in colon carcinomas and in cell lines derived from them (including HT-29). Abundance of calpactin I in such cells is consistent with the possibility that activation of the pp60c-src tyrosine kinase contributes to the origin of human colon cancers.", "contents": "Expression of the gene coding for the light chain of calpactin I (annexin II) in cell lines DiFi, HT-29, and WI-38. Calpactin I (annexin II) light chain gene messages were expressed in the DiFi and HT-29 human colon cancer cell lines, as well as in the diploid lung fibroblast cell line WI-38. However, expression of an approximately 1.0 kb transcript was stronger in DiFi and HT-29 cells than in WI-38 cells. The moderate to strong expression of such transcripts in DiFi and HT-29 cells indicates that the calcium binding protein, calpactin I, may be abundant in colon carcinoma cells. Calpactin I is the major substrate of pp60v-src, a tyrosine-specific protein kinase encoded by v-src, whose cellular homologue c-src also codes for a tyrosine kinase (pp60c-src), known to be activated in colon carcinomas and in cell lines derived from them (including HT-29). Abundance of calpactin I in such cells is consistent with the possibility that activation of the pp60c-src tyrosine kinase contributes to the origin of human colon cancers."} {"id": "PMID:1280034", "title": "Puromycin is a potent and specific inhibitor of tyrosine kinase activity in HL-60 cells.", "content": "The search for specific tyrosine kinase inhibitors constitutes a novel approach to the development of anticancer agents. Puromycin (PM) inhibits protein synthesis by causing the premature release of truncated PM-peptide complexes (PMPs), the structure of which predicts an inhibitory effect on tyrosine kinase activity (21). The present study was undertaken to investigate the effects of a low dose of PM (0.9 microM) on tyrosine kinase activity in HL-60 leukaemic cells. Experiments were specifically controlled to exclude inhibitory effects consequent on protein synthesis blockade. Soluble enzyme extracts derived from PM-treated cells showed attenuated phosphorylation of two independent synthetic tyrosine kinase-specific substrates, the polymer Poly(Glu:Tyr; 4:1) and the peptide substrate Raytide. In contrast, Protein Kinase C-specific activity was unaffected by PM-exposure. It is possible that inhibition was due to metabolites of PM, perhaps PMPs, rather than to PM itself. Whether the inhibition of tyrosine kinase activity observed with the substrates used in this study is equally applicable to all tyrosine kinases, is not yet clear. Nevertheless, low-dose PM could provide a useful tool for dissecting out the role of tyrosine phosphorylation in the regulation and dysregulation of cell growth, and could conceivably prove beneficial in the treatment of tumours in which tyrosine kinase overactivity is linked to oncogenesis.", "contents": "Puromycin is a potent and specific inhibitor of tyrosine kinase activity in HL-60 cells. The search for specific tyrosine kinase inhibitors constitutes a novel approach to the development of anticancer agents. Puromycin (PM) inhibits protein synthesis by causing the premature release of truncated PM-peptide complexes (PMPs), the structure of which predicts an inhibitory effect on tyrosine kinase activity (21). The present study was undertaken to investigate the effects of a low dose of PM (0.9 microM) on tyrosine kinase activity in HL-60 leukaemic cells. Experiments were specifically controlled to exclude inhibitory effects consequent on protein synthesis blockade. Soluble enzyme extracts derived from PM-treated cells showed attenuated phosphorylation of two independent synthetic tyrosine kinase-specific substrates, the polymer Poly(Glu:Tyr; 4:1) and the peptide substrate Raytide. In contrast, Protein Kinase C-specific activity was unaffected by PM-exposure. It is possible that inhibition was due to metabolites of PM, perhaps PMPs, rather than to PM itself. Whether the inhibition of tyrosine kinase activity observed with the substrates used in this study is equally applicable to all tyrosine kinases, is not yet clear. Nevertheless, low-dose PM could provide a useful tool for dissecting out the role of tyrosine phosphorylation in the regulation and dysregulation of cell growth, and could conceivably prove beneficial in the treatment of tumours in which tyrosine kinase overactivity is linked to oncogenesis."} {"id": "PMID:1280037", "title": "Aflatoxins and kwashiorkor in Durban, South Africa.", "content": "The present investigation has indicated that maize seeds stored under various simulated seasonal conditions show a spectrum of fungi that appear as a succession. The aflatoxin-producing fungus, Aspergillus flavus, is favoured by storage conditions of high temperature and humidity (summer and autumn seasons). This coincides with the more frequent admission of children suffering from kwashiorkor at King Edward VIII Hospital in Durban. Aflatoxin analysis was undertaken on 74 children diagnosed at King Edward VIII Hospital in Durban as cases of kwashiorkor, marasmus or underweight (Wellcome classification). The control group consisted of 35 age-matched patients with no symptoms of protein energy malnutrition. Aflatoxins were detected in serum and/or urine from all groups, including the controls. The serum/urine ratio was significantly higher in the kwashiorkor group than in the other groups. The control group, however, had a higher proportion of urine aflatoxins than the kwashiorkor group. These findings were interpreted in terms of impaired liver function in kwashiorkor. Aflatoxins may have a r\u00f4le in the pathogenesis of kwashiorkor, although the present findings do not indicate that they are a causal factor.", "contents": "Aflatoxins and kwashiorkor in Durban, South Africa. The present investigation has indicated that maize seeds stored under various simulated seasonal conditions show a spectrum of fungi that appear as a succession. The aflatoxin-producing fungus, Aspergillus flavus, is favoured by storage conditions of high temperature and humidity (summer and autumn seasons). This coincides with the more frequent admission of children suffering from kwashiorkor at King Edward VIII Hospital in Durban. Aflatoxin analysis was undertaken on 74 children diagnosed at King Edward VIII Hospital in Durban as cases of kwashiorkor, marasmus or underweight (Wellcome classification). The control group consisted of 35 age-matched patients with no symptoms of protein energy malnutrition. Aflatoxins were detected in serum and/or urine from all groups, including the controls. The serum/urine ratio was significantly higher in the kwashiorkor group than in the other groups. The control group, however, had a higher proportion of urine aflatoxins than the kwashiorkor group. These findings were interpreted in terms of impaired liver function in kwashiorkor. Aflatoxins may have a r\u00f4le in the pathogenesis of kwashiorkor, although the present findings do not indicate that they are a causal factor."} {"id": "PMID:1280038", "title": "Relation of peak total serum bilirubin concentrations to neurodevelopmental outcome at 2 years of age in premature African neonates.", "content": "As part of a wider survey of the neurodevelopmental outcome of neonates who received intensive care for various morbidities in the Middle-Belt region of Nigeria, the relationship between peak total serum bilirubin (PTSB) concentrations in the neonatal period and neurodevelopmental status at 2 years of age was evaluated in 159 children available for follow-up and assessment. The prevalence of handicaps (minor and major) increased consistently with increase in the PTSB concentration, commencing in the range of 151-200 mumol/l. Major handicaps evolved in association with PTSB concentrations above 201 mumol/l. The handicaps consisted mainly of cerebral palsy and mental retardation. Children with handicaps (minor and major) experienced greater PTSB concentrations than those with a normal neurodevelopmental outcome. The emergence of major handicaps from a mean (SD) moderate peak hyperbilirubinaemia of 241.1 (35.9) mumol/l in the African neonate is worthy of note and cause for concern.", "contents": "Relation of peak total serum bilirubin concentrations to neurodevelopmental outcome at 2 years of age in premature African neonates. As part of a wider survey of the neurodevelopmental outcome of neonates who received intensive care for various morbidities in the Middle-Belt region of Nigeria, the relationship between peak total serum bilirubin (PTSB) concentrations in the neonatal period and neurodevelopmental status at 2 years of age was evaluated in 159 children available for follow-up and assessment. The prevalence of handicaps (minor and major) increased consistently with increase in the PTSB concentration, commencing in the range of 151-200 mumol/l. Major handicaps evolved in association with PTSB concentrations above 201 mumol/l. The handicaps consisted mainly of cerebral palsy and mental retardation. Children with handicaps (minor and major) experienced greater PTSB concentrations than those with a normal neurodevelopmental outcome. The emergence of major handicaps from a mean (SD) moderate peak hyperbilirubinaemia of 241.1 (35.9) mumol/l in the African neonate is worthy of note and cause for concern."} {"id": "PMID:1280039", "title": "Spotted fever in Hong Kong.", "content": "A previously healthy 7-year-old Hong Kong-born Caucasian child developed sudden onset fever, followed by a generalized rash and systemic symptoms of rigor and prostration, mucous membrane involvement (conjunctivitis) and arthralgia. He lives in a rural area of Hong Kong and has been in contact with various domestic animals--rodents, dogs and cows. Chloramphenicol 50 mg/kg/day was given on day 4 with rapid response. Subsequent Weil-Felix test and specific serology suggested the diagnosis of rickettsial infection of the spotted fever group. To our knowledge, this is the first confirmed case of spotted fever reported in Hong Kong.", "contents": "Spotted fever in Hong Kong. A previously healthy 7-year-old Hong Kong-born Caucasian child developed sudden onset fever, followed by a generalized rash and systemic symptoms of rigor and prostration, mucous membrane involvement (conjunctivitis) and arthralgia. He lives in a rural area of Hong Kong and has been in contact with various domestic animals--rodents, dogs and cows. Chloramphenicol 50 mg/kg/day was given on day 4 with rapid response. Subsequent Weil-Felix test and specific serology suggested the diagnosis of rickettsial infection of the spotted fever group. To our knowledge, this is the first confirmed case of spotted fever reported in Hong Kong."} {"id": "PMID:1280040", "title": "The molecular epidemiology of rotavirus-associated gastro-enteritis in the Transkei, southern Africa.", "content": "Rotaviruses were detected in 32.8% (71/216) of stool specimens collected from young children with gastro-enteritis attending the Rehydration Unit at Umtata General Hospital between April 1988 and March 1989. A seasonal distribution was observed with an increase in numbers shedding the virus during the colder months of the year. Based on variations in the migration pattern of the RNA genome segments when passed through polyacrylamide gels, 14 different electrophoretypes were identified: 69% were long patterns and 27% were short patterns. A single dominant long electrophoretype persisted throughout the 12-month study period, whereas 13 other minor types co-circulated at varying intervals. Mixed infections were observed in three cases, including one infant who was infected with both a long (Wa-like) virus and a short (DS-1-like) virus.", "contents": "The molecular epidemiology of rotavirus-associated gastro-enteritis in the Transkei, southern Africa. Rotaviruses were detected in 32.8% (71/216) of stool specimens collected from young children with gastro-enteritis attending the Rehydration Unit at Umtata General Hospital between April 1988 and March 1989. A seasonal distribution was observed with an increase in numbers shedding the virus during the colder months of the year. Based on variations in the migration pattern of the RNA genome segments when passed through polyacrylamide gels, 14 different electrophoretypes were identified: 69% were long patterns and 27% were short patterns. A single dominant long electrophoretype persisted throughout the 12-month study period, whereas 13 other minor types co-circulated at varying intervals. Mixed infections were observed in three cases, including one infant who was infected with both a long (Wa-like) virus and a short (DS-1-like) virus."} {"id": "PMID:1280041", "title": "Paediatric empyema thoracis in Zaria, Nigeria.", "content": "From 1977 to 1986 at the Ahmadu Bello University Hospital in Zaria, the diagnosis of empyema thoracis was made in 150 children representing 0.35% of all paediatric admissions. Empyema was a complication of pneumonia in 98 of 100 cases reviewed, of whom 70 were 3 years old or younger. There was no sex or side preference. Fifty-nine patients were severely ill on admission, with a mean symptom duration of 21 days. In many of them, anaemia, protein-energy malnutrition, measles and gastro-enteritis were present as associated illnesses. Staphylococcus aureus was the most frequent bacterial isolate (39%), of which 83% of the cultures were sensitive to cloxacillin. Adequate rehydration, systemic antibiotics and tube thoracostomy drainage performed in 80 patients were more successful than repeated needle aspiration. Fourteen of the children died, six absconded and 80 were discharged home.", "contents": "Paediatric empyema thoracis in Zaria, Nigeria. From 1977 to 1986 at the Ahmadu Bello University Hospital in Zaria, the diagnosis of empyema thoracis was made in 150 children representing 0.35% of all paediatric admissions. Empyema was a complication of pneumonia in 98 of 100 cases reviewed, of whom 70 were 3 years old or younger. There was no sex or side preference. Fifty-nine patients were severely ill on admission, with a mean symptom duration of 21 days. In many of them, anaemia, protein-energy malnutrition, measles and gastro-enteritis were present as associated illnesses. Staphylococcus aureus was the most frequent bacterial isolate (39%), of which 83% of the cultures were sensitive to cloxacillin. Adequate rehydration, systemic antibiotics and tube thoracostomy drainage performed in 80 patients were more successful than repeated needle aspiration. Fourteen of the children died, six absconded and 80 were discharged home."} {"id": "PMID:1280042", "title": "Serological tests in cerebrospinal fluid for congenital syphilis in central Africa.", "content": "Serological tests were performed in the cerebrospinal fluid (CSF) of 13 children with active congenital syphilis (presence of specific IgM FTA-ABS antibodies) and of seven seropositive children with no active syphilis (FTA-ABS IgM-negative) born to syphilitic treated mothers in Libreville, Gabon. Antibodies against treponema were measured by the Venereal Disease Research Laboratory test (VDRL), the Treponema pallidum haemagglutination assay (TPHA) and the fluorescent treponema antibody absorption tests (FTA-ABS IgG and IgM). Of the 13 children with active syphilis, seven had a positive FTA-ABS IgG in the CSF. The result of this test was not correlated with the severity of clinical features, CSF protein levels or number of CSF white blood cells. The CSF-TPHA test was positive in four out of 12 children, and the CSF-VDRL test was negative in all the children with active congenital syphilis. One of the seven newborns with mother-transmitted antibodies had a positive FTA-ABS and TPHA in the CSF. These data show that the VDRL is not sensitive enough to diagnose congenital neurosyphilis, and that FTA-ABS or, at least, TPHA are convenient, sometimes with false-positive results, when a sophisticated method of detecting specific IgM in CSF is not available.", "contents": "Serological tests in cerebrospinal fluid for congenital syphilis in central Africa. Serological tests were performed in the cerebrospinal fluid (CSF) of 13 children with active congenital syphilis (presence of specific IgM FTA-ABS antibodies) and of seven seropositive children with no active syphilis (FTA-ABS IgM-negative) born to syphilitic treated mothers in Libreville, Gabon. Antibodies against treponema were measured by the Venereal Disease Research Laboratory test (VDRL), the Treponema pallidum haemagglutination assay (TPHA) and the fluorescent treponema antibody absorption tests (FTA-ABS IgG and IgM). Of the 13 children with active syphilis, seven had a positive FTA-ABS IgG in the CSF. The result of this test was not correlated with the severity of clinical features, CSF protein levels or number of CSF white blood cells. The CSF-TPHA test was positive in four out of 12 children, and the CSF-VDRL test was negative in all the children with active congenital syphilis. One of the seven newborns with mother-transmitted antibodies had a positive FTA-ABS and TPHA in the CSF. These data show that the VDRL is not sensitive enough to diagnose congenital neurosyphilis, and that FTA-ABS or, at least, TPHA are convenient, sometimes with false-positive results, when a sophisticated method of detecting specific IgM in CSF is not available."} {"id": "PMID:1280043", "title": "The increased risk of developing tuberculosis in children with malignancy.", "content": "Tuberculosis (TB) remains a serious health problem in many developing countries. As impaired immunity is closely associated with the pathogenesis of TB, an increase in the incidence of this disease among patients with cancer is anticipated. This retrospective analysis of children from an area of high TB prevalence was done to determine the incidence of TB in children treated for cancer. Of 390 children admitted between 1983 and 1990, 278 were evaluated. Standardized morbidity ratios showed that children with malignancies had an 11-times greater chance of developing TB than children of the same age group in the general population. The highest incidence occurred in children with Wilms' tumour (5 of 41). In the majority of patients (77%), TB was diagnosed during the initial period of hospitalization and chest X-ray suggested post-primary TB. This suggests reactivation of quiescent mycobacteria during a period of impaired immunity. Children from an area with a high incidence of TB who develop malignancy should be actively investigated for tuberculosis prior to the start of immunosuppressive therapy. We speculate that these children would benefit from a course of preventive anti-tuberculosis treatment at the start of chemotherapy.", "contents": "The increased risk of developing tuberculosis in children with malignancy. Tuberculosis (TB) remains a serious health problem in many developing countries. As impaired immunity is closely associated with the pathogenesis of TB, an increase in the incidence of this disease among patients with cancer is anticipated. This retrospective analysis of children from an area of high TB prevalence was done to determine the incidence of TB in children treated for cancer. Of 390 children admitted between 1983 and 1990, 278 were evaluated. Standardized morbidity ratios showed that children with malignancies had an 11-times greater chance of developing TB than children of the same age group in the general population. The highest incidence occurred in children with Wilms' tumour (5 of 41). In the majority of patients (77%), TB was diagnosed during the initial period of hospitalization and chest X-ray suggested post-primary TB. This suggests reactivation of quiescent mycobacteria during a period of impaired immunity. Children from an area with a high incidence of TB who develop malignancy should be actively investigated for tuberculosis prior to the start of immunosuppressive therapy. We speculate that these children would benefit from a course of preventive anti-tuberculosis treatment at the start of chemotherapy."} {"id": "PMID:1280044", "title": "Prolonged rupture of membranes and neonatal outcome in a developing country.", "content": "The neonatal outcomes in 109 pregnancies complicated by prolonged rupture of the fetal membranes were studied over a 3-year period. The overall neonatal mortality was 29 (26.6%). Nineteen of these deaths were from infections, of which 12 were pneumonia. There was also a high morbidity rate of 68.8%. Neonatal sepsis, cardiorespiratory depression at birth and prematurity were the most significant complications. Forty-eight (44%) of the infants in the study group had an infection, in contrast with three (2.9%) in the control group (p < 0.0001). No protective effect or benefit from prolonged rupture of fetal membranes in relation to the development of respiratory distress syndrome was demonstrated.", "contents": "Prolonged rupture of membranes and neonatal outcome in a developing country. The neonatal outcomes in 109 pregnancies complicated by prolonged rupture of the fetal membranes were studied over a 3-year period. The overall neonatal mortality was 29 (26.6%). Nineteen of these deaths were from infections, of which 12 were pneumonia. There was also a high morbidity rate of 68.8%. Neonatal sepsis, cardiorespiratory depression at birth and prematurity were the most significant complications. Forty-eight (44%) of the infants in the study group had an infection, in contrast with three (2.9%) in the control group (p < 0.0001). No protective effect or benefit from prolonged rupture of fetal membranes in relation to the development of respiratory distress syndrome was demonstrated."} {"id": "PMID:1280045", "title": "Morbidity and mortality in the Special Care Baby Unit of New Mulago Hospital, Kampala.", "content": "The morbidity and mortality of admissions to the Special Care Baby Unit at New Mulago Hospital, Kampala are described for 1598 infants seen during the 12-month period of 1989. The overall neonatal mortality rate on the Unit was 18.0%, which has shown only slight improvement during the period 1984-1989. The major causes of death were, in descending order of frequency: birth asphyxia, respiratory distress syndrome, aspiration syndromes, very low birthweight, infection, anaemia and congenital malformations. Birth asphyxia was the most common cause of death in infants weighing over 2500 g while respiratory distress syndrome predominated among deaths below 2500 g. Birth injuries and transient tachypnoea of the newborn were also common reasons for admission. Difficulties of caring for infants requiring special care in a developing country are emphasized. These include inadequate equipment and supplies, poor investigative facilities and scarcity of well trained personnel. The situation is further aggravated by low morale among health workers due to poor working conditions.", "contents": "Morbidity and mortality in the Special Care Baby Unit of New Mulago Hospital, Kampala. The morbidity and mortality of admissions to the Special Care Baby Unit at New Mulago Hospital, Kampala are described for 1598 infants seen during the 12-month period of 1989. The overall neonatal mortality rate on the Unit was 18.0%, which has shown only slight improvement during the period 1984-1989. The major causes of death were, in descending order of frequency: birth asphyxia, respiratory distress syndrome, aspiration syndromes, very low birthweight, infection, anaemia and congenital malformations. Birth asphyxia was the most common cause of death in infants weighing over 2500 g while respiratory distress syndrome predominated among deaths below 2500 g. Birth injuries and transient tachypnoea of the newborn were also common reasons for admission. Difficulties of caring for infants requiring special care in a developing country are emphasized. These include inadequate equipment and supplies, poor investigative facilities and scarcity of well trained personnel. The situation is further aggravated by low morale among health workers due to poor working conditions."} {"id": "PMID:1280046", "title": "Malaria parasitaemia in neonates with predisposing risk factors for neonatal sepsis: report of six cases.", "content": "In a study of neonatal malaria at the University of Benin Teaching Hospital, we documented the features of six neonates in an effort to highlight that the manifestations of malaria in the newborn cannot be readily distinguished from those of neonatal sepsis. Maternal peripartum fever, an important identifiable risk factor for neonatal sepsis, also featured prominently in the mothers of these babies. These mothers ingested pyrimethamine weekly in the course of their pregnancy. All six neonates were critically ill. Their cultures of blood, CSF and urine for bacterial pathogens yielded no growth and they were unresponsive to conventional antibiotics. The diagnosis of malaria should be considered, in spite of regular maternal ingestion of antimalarial prophylaxis with pyrimethamine, in critically ill neonates in malarious areas. All six neonates responded satisfactorily to oral doses of chloroquine. We therefore suggest that a blood film for malaria parasites be included in screening for neonatal sepsis as part of the initial work-up.", "contents": "Malaria parasitaemia in neonates with predisposing risk factors for neonatal sepsis: report of six cases. In a study of neonatal malaria at the University of Benin Teaching Hospital, we documented the features of six neonates in an effort to highlight that the manifestations of malaria in the newborn cannot be readily distinguished from those of neonatal sepsis. Maternal peripartum fever, an important identifiable risk factor for neonatal sepsis, also featured prominently in the mothers of these babies. These mothers ingested pyrimethamine weekly in the course of their pregnancy. All six neonates were critically ill. Their cultures of blood, CSF and urine for bacterial pathogens yielded no growth and they were unresponsive to conventional antibiotics. The diagnosis of malaria should be considered, in spite of regular maternal ingestion of antimalarial prophylaxis with pyrimethamine, in critically ill neonates in malarious areas. All six neonates responded satisfactorily to oral doses of chloroquine. We therefore suggest that a blood film for malaria parasites be included in screening for neonatal sepsis as part of the initial work-up."} {"id": "PMID:1280047", "title": "Fetal anaemia in malarious areas: its causes and significance.", "content": "This analysis reviews published studies of cord haemoglobin values in developing countries and compares findings for populations that are either exposed or not exposed to malaria. The review indicates: first, that fetal anaemia is common in women with chronic moderate-to-severe iron deficiency anaemia; second, that a severe degree of fetal anaemia is reported in several areas where malaria in pregnancy is common. Different levels of fetal anaemia or polycythaemia arise in relation to the duration and severity of maternal anaemia during pregnancy, but in malarious areas the fetal anaemia appears to be out of proportion to the level of maternal anaemia. Haemoglobinopathies are likely to play a contributory role in causing fetal anaemia. The concept is advanced that malaria may contribute to fetal anaemia as a result of immune haemolysis of sensitized red cells. Sensitization could be from malaria antibodies and antigens which cross the placenta. Further evidence is required to prove this hypothesis. The importance of fetal anaemia is that it is likely to relate to the pattern and risk of developing anaemia in infancy.", "contents": "Fetal anaemia in malarious areas: its causes and significance. This analysis reviews published studies of cord haemoglobin values in developing countries and compares findings for populations that are either exposed or not exposed to malaria. The review indicates: first, that fetal anaemia is common in women with chronic moderate-to-severe iron deficiency anaemia; second, that a severe degree of fetal anaemia is reported in several areas where malaria in pregnancy is common. Different levels of fetal anaemia or polycythaemia arise in relation to the duration and severity of maternal anaemia during pregnancy, but in malarious areas the fetal anaemia appears to be out of proportion to the level of maternal anaemia. Haemoglobinopathies are likely to play a contributory role in causing fetal anaemia. The concept is advanced that malaria may contribute to fetal anaemia as a result of immune haemolysis of sensitized red cells. Sensitization could be from malaria antibodies and antigens which cross the placenta. Further evidence is required to prove this hypothesis. The importance of fetal anaemia is that it is likely to relate to the pattern and risk of developing anaemia in infancy."} {"id": "PMID:1280048", "title": "Benign acute childhood myositis in Kuwait.", "content": "Ten children, three girls and seven boys, aged 4-10 years, were admitted with benign acute childhood myositis during spring and winter months (March 1988 to March 1990). They presented with an acute onset of symmetrical calf muscle pain and tenderness, weakness and inability to walk a few days after a flu-like illness. All had raised serum creatine kinase and a normal erythrocyte sedimentation rate, and the majority had low peripheral white blood cell counts with relative lymphocytosis. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were found to be raised in four patients. Virological studies performed in six children gave negative results. Full clinical recovery was achieved within 1-7 days. One child developed a second episode. These ten cases of benign acute childhood myositis are the first to be reported from this region.", "contents": "Benign acute childhood myositis in Kuwait. Ten children, three girls and seven boys, aged 4-10 years, were admitted with benign acute childhood myositis during spring and winter months (March 1988 to March 1990). They presented with an acute onset of symmetrical calf muscle pain and tenderness, weakness and inability to walk a few days after a flu-like illness. All had raised serum creatine kinase and a normal erythrocyte sedimentation rate, and the majority had low peripheral white blood cell counts with relative lymphocytosis. Serum aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were found to be raised in four patients. Virological studies performed in six children gave negative results. Full clinical recovery was achieved within 1-7 days. One child developed a second episode. These ten cases of benign acute childhood myositis are the first to be reported from this region."} {"id": "PMID:1280049", "title": "Ultrasound detection rate of childhood urolithiasis.", "content": "A retrospective study of 42 children with 45 proven urinary tract stones who had had intravenous urography (IVU), ultrasound examination and a plain abdominal X-ray (KUB) was undertaken in order to evaluate the prediction rate of each method. Ultrasound was more sensitive than KUB (91% vs 80%) in detecting stones. All renal stones were detected by ultrasound. KUB was superior to ultrasound in detecting ureteral stones (66.6% vs 55.5%). All stones were detected by the combination of ultrasound and KUB. Two renal radiolucent stones were missed by IVU. The results of this study suggest that the combination of ultrasound examination and KUB is more sensitive in detecting stones than IVU and is more convenient and less invasive.", "contents": "Ultrasound detection rate of childhood urolithiasis. A retrospective study of 42 children with 45 proven urinary tract stones who had had intravenous urography (IVU), ultrasound examination and a plain abdominal X-ray (KUB) was undertaken in order to evaluate the prediction rate of each method. Ultrasound was more sensitive than KUB (91% vs 80%) in detecting stones. All renal stones were detected by ultrasound. KUB was superior to ultrasound in detecting ureteral stones (66.6% vs 55.5%). All stones were detected by the combination of ultrasound and KUB. Two renal radiolucent stones were missed by IVU. The results of this study suggest that the combination of ultrasound examination and KUB is more sensitive in detecting stones than IVU and is more convenient and less invasive."} {"id": "PMID:1280050", "title": "Hepatitis B serology among the Palestinian population.", "content": "A total of 778 blood samples collected from Palestinian subjects between September 1989 and March 1990 were tested for hepatitis B surface antigen (HBsAg) and when negative for antibody to hepatitis B surface antigen (anti-HBs). The emphasis of the survey was on the younger population with 85% of those tested under the age of 30 years. The prevalence of positive markers (HBsAg or anti-HBs) rose progressively with age, being 1% under the age of 5 years and reaching 47% in those aged between 30 and 50 years. The results clearly show that this infection is endemic in our population. A vaccination policy is discussed. The most important finding was the very low prevalence of the infection in those under 5 years of age, indicating the minor role played by perinatal transmission in our community. Thus, an effective immunization programme does not need to target newborns.", "contents": "Hepatitis B serology among the Palestinian population. A total of 778 blood samples collected from Palestinian subjects between September 1989 and March 1990 were tested for hepatitis B surface antigen (HBsAg) and when negative for antibody to hepatitis B surface antigen (anti-HBs). The emphasis of the survey was on the younger population with 85% of those tested under the age of 30 years. The prevalence of positive markers (HBsAg or anti-HBs) rose progressively with age, being 1% under the age of 5 years and reaching 47% in those aged between 30 and 50 years. The results clearly show that this infection is endemic in our population. A vaccination policy is discussed. The most important finding was the very low prevalence of the infection in those under 5 years of age, indicating the minor role played by perinatal transmission in our community. Thus, an effective immunization programme does not need to target newborns."} {"id": "PMID:1280051", "title": "Glucose-galactose malabsorption with renal stones in a Saudi child.", "content": "A case of glucose-galactose malabsorption in an 18-month-old Saudi girl is presented. She had associated bilateral renal stones with impaired renal function. Dietary therapy improved her malabsorption and the renal stones were cleared by extracorporeal shortwave lithotripsy.", "contents": "Glucose-galactose malabsorption with renal stones in a Saudi child. A case of glucose-galactose malabsorption in an 18-month-old Saudi girl is presented. She had associated bilateral renal stones with impaired renal function. Dietary therapy improved her malabsorption and the renal stones were cleared by extracorporeal shortwave lithotripsy."} {"id": "PMID:1280052", "title": "Disappearing CT lesions in focal seizures.", "content": "A case of focal seizures with right hemiparesis in a 6-year-old Indian girl is presented. CT scan showed four ring-enhancing lesions in the left cortex. She was treated with phenytoin and a course of praziquantel. The hemiparesis recovered in 3 weeks and a repeat CT scan after 2 months was normal. Arbitrary use of anti-tuberculous therapy in Indian children with focal lesions in the brain is not recommended as the lesions are often due to cysticercosis.", "contents": "Disappearing CT lesions in focal seizures. A case of focal seizures with right hemiparesis in a 6-year-old Indian girl is presented. CT scan showed four ring-enhancing lesions in the left cortex. She was treated with phenytoin and a course of praziquantel. The hemiparesis recovered in 3 weeks and a repeat CT scan after 2 months was normal. Arbitrary use of anti-tuberculous therapy in Indian children with focal lesions in the brain is not recommended as the lesions are often due to cysticercosis."} {"id": "PMID:1280053", "title": "Infantile hydrocephalus in the south-western region of Saudi Arabia.", "content": "During the period January 1988 to December 1990, the overall incidence of infantile hydrocephalus in the south-western region of Saudi Arabia was 0.81/1000. The series comprised 61 infants affected by infantile hydrocephalus. The total number of live births in this period was 74,923. Hydrocephalus associated with spinal dysraphism (spina bifida cystica and encephalocoele) constituted 24 cases (39.3%), and there was aqueduct stenosis in 10 cases (16.4%). Nine cases (11.9%) were post-meningitic, and seven (14.8%) post-haemorrhagic. There was Dandy-Walker malformation in five cases (8.2%), three (4.9%) had congenital idiopathic hydrocephalus, two (3.3%) congenital toxoplasmosis, and one (1.6%) isolated Arnold Chiari malformation. There were congenital causes in 45 cases, 73.7% of all the cases in this series (incidence: 0.6/1000 births). Of the remaining 16 cases (26.3%) which were due to postnatal factors, seven (11.5%) were caused by acquired cerebral haemorrhage, only two of them being premature, and the other nine (14.8%) were due to meningitis. The data indicate the predominance of prenatal causes of infantile hydrocephalus and the relatively low contribution of extreme prematurity. This is possibly due to the high mortality of this group of infants in this region.", "contents": "Infantile hydrocephalus in the south-western region of Saudi Arabia. During the period January 1988 to December 1990, the overall incidence of infantile hydrocephalus in the south-western region of Saudi Arabia was 0.81/1000. The series comprised 61 infants affected by infantile hydrocephalus. The total number of live births in this period was 74,923. Hydrocephalus associated with spinal dysraphism (spina bifida cystica and encephalocoele) constituted 24 cases (39.3%), and there was aqueduct stenosis in 10 cases (16.4%). Nine cases (11.9%) were post-meningitic, and seven (14.8%) post-haemorrhagic. There was Dandy-Walker malformation in five cases (8.2%), three (4.9%) had congenital idiopathic hydrocephalus, two (3.3%) congenital toxoplasmosis, and one (1.6%) isolated Arnold Chiari malformation. There were congenital causes in 45 cases, 73.7% of all the cases in this series (incidence: 0.6/1000 births). Of the remaining 16 cases (26.3%) which were due to postnatal factors, seven (11.5%) were caused by acquired cerebral haemorrhage, only two of them being premature, and the other nine (14.8%) were due to meningitis. The data indicate the predominance of prenatal causes of infantile hydrocephalus and the relatively low contribution of extreme prematurity. This is possibly due to the high mortality of this group of infants in this region."} {"id": "PMID:1280054", "title": "Fatal myeloencephalopathy due to intrathecal vincristine administration.", "content": "Vincristine was accidentally given intrathecally to a child with leukaemia, producing sensory and motor dysfunction followed by encephalopathy and death. Separate times for administering vincristine and intrathecal therapy is recommended.", "contents": "Fatal myeloencephalopathy due to intrathecal vincristine administration. Vincristine was accidentally given intrathecally to a child with leukaemia, producing sensory and motor dysfunction followed by encephalopathy and death. Separate times for administering vincristine and intrathecal therapy is recommended."} {"id": "PMID:1280055", "title": "Analysis of macromolecular biosynthesis to define the quinolone-induced postantibiotic effect in Escherichia coli.", "content": "Quinolones inhibit DNA gyrase, and the major effects of this inhibition are on replication and transcription of DNA. The postantibiotic effect (PAE) refers to continued inhibition of cell division, in terms of the viable count, following transient exposure to an antibiotic. Previous work has shown that quinolone-treated cells have not fully recovered by the time the classically defined PAE has ended. We describe the PAE of the quinolones CI-960, enoxacin, and ciprofloxacin on macromolecular biosynthesis in the clinical isolate Escherichia coli J96 in an attempt to relate the PAE to the time that it actually takes for the cells to recover fully. DNA synthesis was inhibited immediately upon exposure to these quinolones at 0.5x or 0.75x the MIC. This inhibition continued for several hours following quinolone removal. The effects of these quinolones on RNA and protein synthesis varied; enoxacin treatment at 0.5x the MIC resulted in an increase of over 60% in both RNA and protein synthesis per unit of cell mass, while ciprofloxacin and CI-960 at that level had no significant effects on either RNA or protein synthesis. The effects of enoxacin and ciprofloxacin on bacterial protein profiles were also distinguishable, and these changes corresponded to their PAE on DNA synthesis. Throughout the study, all measures of the physiological status of the cells returned to normal by the time DNA synthesis per unit of cell mass did so. These results suggest that DNA synthesis per unit of cell mass provides an accurate measure of the time required for quinolone-treated cells to recover fully.", "contents": "Analysis of macromolecular biosynthesis to define the quinolone-induced postantibiotic effect in Escherichia coli. Quinolones inhibit DNA gyrase, and the major effects of this inhibition are on replication and transcription of DNA. The postantibiotic effect (PAE) refers to continued inhibition of cell division, in terms of the viable count, following transient exposure to an antibiotic. Previous work has shown that quinolone-treated cells have not fully recovered by the time the classically defined PAE has ended. We describe the PAE of the quinolones CI-960, enoxacin, and ciprofloxacin on macromolecular biosynthesis in the clinical isolate Escherichia coli J96 in an attempt to relate the PAE to the time that it actually takes for the cells to recover fully. DNA synthesis was inhibited immediately upon exposure to these quinolones at 0.5x or 0.75x the MIC. This inhibition continued for several hours following quinolone removal. The effects of these quinolones on RNA and protein synthesis varied; enoxacin treatment at 0.5x the MIC resulted in an increase of over 60% in both RNA and protein synthesis per unit of cell mass, while ciprofloxacin and CI-960 at that level had no significant effects on either RNA or protein synthesis. The effects of enoxacin and ciprofloxacin on bacterial protein profiles were also distinguishable, and these changes corresponded to their PAE on DNA synthesis. Throughout the study, all measures of the physiological status of the cells returned to normal by the time DNA synthesis per unit of cell mass did so. These results suggest that DNA synthesis per unit of cell mass provides an accurate measure of the time required for quinolone-treated cells to recover fully."} {"id": "PMID:1280056", "title": "Salicylate-inducible antibiotic resistance in Pseudomonas cepacia associated with absence of a pore-forming outer membrane protein.", "content": "The most common mechanism of antibiotic resistance in multiply resistant Pseudomonas cepacia is decreased porin-mediated outer membrane permeability. In some gram-negative organisms this form of antibiotic resistance can be induced by growth in the presence of weak acids, such as salicylates, which suppress porin synthesis. To determine the effects of salicylates on outer membrane permeability of P. cepacia, a susceptible laboratory strain, 249-2, was grown in 10 mM sodium salicylate. Antibiotic susceptibility and uptake, as well as outer membrane protein patterns, were compared between strain 249-2 grown with and without salicylates. The MICs of chloramphenicol, trimethoprim, ciprofloxacin, and ceftazidime were compared between organisms grown in standard and salicylate-containing medium and are as follows: chloramphenicol, 12.5 versus 100 micrograms/ml; trimethoprim, 0.78 versus 3.125 micrograms/ml; ciprofloxacin, 0.4 versus 1.56 micrograms/ml; ceftazidime, 3.125 versus 3.125 micrograms/ml. The permeability of beta-lactam antibiotics was calculated from the rate of hydrolysis of the chromogenic cephalosporin, PADAC. There was no significant difference between strains grown in the presence and absence of salicylate. By using high-pressure liquid chromatography quantitation of loss from culture medium, the effect of 10 mM salicylate on the cellular permeability of chloramphenicol was measured in strain 249-2 by introduction of a plasmid which encodes production of chloramphenicol acetyltransferase. After 1 h of incubation, 18.5% +/- 1.54% versus 70.1% +/- 3.52%, and after 2 h, 4.20% +/- 1.65% versus 41.90% +/- 2.16% remained in supernatants from organisms grown in the absence and presence of 10 mM salicylate, respectively. Outer membrane protein pattern analysis demonstrated the absence of a protein of apparent molecular weight of 40,000 when strain 249-2 was grown in the presence of 10 mM salicylate. To determine whether this protein functioned as a porin, reconstituted membrane vesicles were constructed to assess antibiotic permeability. Vesicles constructed with this salicylate-suppressible outer membrane protein (OpcS) were permeable to chloramphenicol but not to penicillin G. These findings suggest that OpcS is a selective, antibiotic-permeable porin which can be suppressed by growth in the presence of salicylate. Further investigation will be required to determine the biochemical effects of salicylate on porin synthesis.", "contents": "Salicylate-inducible antibiotic resistance in Pseudomonas cepacia associated with absence of a pore-forming outer membrane protein. The most common mechanism of antibiotic resistance in multiply resistant Pseudomonas cepacia is decreased porin-mediated outer membrane permeability. In some gram-negative organisms this form of antibiotic resistance can be induced by growth in the presence of weak acids, such as salicylates, which suppress porin synthesis. To determine the effects of salicylates on outer membrane permeability of P. cepacia, a susceptible laboratory strain, 249-2, was grown in 10 mM sodium salicylate. Antibiotic susceptibility and uptake, as well as outer membrane protein patterns, were compared between strain 249-2 grown with and without salicylates. The MICs of chloramphenicol, trimethoprim, ciprofloxacin, and ceftazidime were compared between organisms grown in standard and salicylate-containing medium and are as follows: chloramphenicol, 12.5 versus 100 micrograms/ml; trimethoprim, 0.78 versus 3.125 micrograms/ml; ciprofloxacin, 0.4 versus 1.56 micrograms/ml; ceftazidime, 3.125 versus 3.125 micrograms/ml. The permeability of beta-lactam antibiotics was calculated from the rate of hydrolysis of the chromogenic cephalosporin, PADAC. There was no significant difference between strains grown in the presence and absence of salicylate. By using high-pressure liquid chromatography quantitation of loss from culture medium, the effect of 10 mM salicylate on the cellular permeability of chloramphenicol was measured in strain 249-2 by introduction of a plasmid which encodes production of chloramphenicol acetyltransferase. After 1 h of incubation, 18.5% +/- 1.54% versus 70.1% +/- 3.52%, and after 2 h, 4.20% +/- 1.65% versus 41.90% +/- 2.16% remained in supernatants from organisms grown in the absence and presence of 10 mM salicylate, respectively. Outer membrane protein pattern analysis demonstrated the absence of a protein of apparent molecular weight of 40,000 when strain 249-2 was grown in the presence of 10 mM salicylate. To determine whether this protein functioned as a porin, reconstituted membrane vesicles were constructed to assess antibiotic permeability. Vesicles constructed with this salicylate-suppressible outer membrane protein (OpcS) were permeable to chloramphenicol but not to penicillin G. These findings suggest that OpcS is a selective, antibiotic-permeable porin which can be suppressed by growth in the presence of salicylate. Further investigation will be required to determine the biochemical effects of salicylate on porin synthesis."} {"id": "PMID:1280057", "title": "Azithromycin-induced block of elementary body formation in Chlamydia trachomatis.", "content": "The mechanism of action of azithromycin on the murine strain of Chlamydia trachomatis grown in tissue culture epithelial cells is addressed. Azithromycin at a concentration of 100 ng/ml inhibits chlamydial growth in tissue culture, a value that agrees well with prior in vitro data from human strains of C. trachomatis grown in tissue culture. By morphological criteria, the block to chlamydial growth appears to occur early in its life cycle. Azithromycin is not directly toxic to chlamydial elementary bodies but does inhibit chlamydial protein synthesis in chlamydia-infected cells. This inhibition appears quite general in nature and is rapid. It is further shown that azithromycin does not directly inhibit mRNA synthesis. Azithromycin blocks chlamydial protein synthesis in host cell-free chlamydial reticulate bodies in a manner similar to its inhibition in infected cells, albeit at slightly higher concentrations. The inhibition of chlamydial protein synthesis following a brief exposure to azithromycin is more long lasting than that following a brief exposure to erythromycin.", "contents": "Azithromycin-induced block of elementary body formation in Chlamydia trachomatis. The mechanism of action of azithromycin on the murine strain of Chlamydia trachomatis grown in tissue culture epithelial cells is addressed. Azithromycin at a concentration of 100 ng/ml inhibits chlamydial growth in tissue culture, a value that agrees well with prior in vitro data from human strains of C. trachomatis grown in tissue culture. By morphological criteria, the block to chlamydial growth appears to occur early in its life cycle. Azithromycin is not directly toxic to chlamydial elementary bodies but does inhibit chlamydial protein synthesis in chlamydia-infected cells. This inhibition appears quite general in nature and is rapid. It is further shown that azithromycin does not directly inhibit mRNA synthesis. Azithromycin blocks chlamydial protein synthesis in host cell-free chlamydial reticulate bodies in a manner similar to its inhibition in infected cells, albeit at slightly higher concentrations. The inhibition of chlamydial protein synthesis following a brief exposure to azithromycin is more long lasting than that following a brief exposure to erythromycin."} {"id": "PMID:1280058", "title": "Inhibition of Moloney murine leukemia virus reverse transcriptase activity by tetrahydroxyxanthones isolated from the Chinese herb, Tripterospermum lanceolatum (Hyata).", "content": "Five tetrahydroxyxanthones (THXs) isolated from Tripterospermum lanceolatum (Hyata) have been shown to have a strong inhibitory effect on Moloney murine leukemia virus reverse transcriptase (Mo-MLV RT) activity when (rA)n-(dT)15 and (rC)n-(dT)12-18 were used as template-primers. 50% inhibitory concentrations of 1,3,5,6-THX, 2,3,6,7-THX 1,3,6,7-THX, 3,4,5,6-THX, and 3,4,6,7-THX were determined to be 0.15, 0.27, 0.58, 0.12, and 0.12 microM, respectively. Their effects were concentration-dependent, and the mode of inhibition was found to be by competitive inhibition with respect to template-primer. The tetrahydroxyl groups of THXs were shown to be important for their inhibitory activity. Acylation of THXs with various groups resulted in a moderate or strong decrease in their inhibitory activity.", "contents": "Inhibition of Moloney murine leukemia virus reverse transcriptase activity by tetrahydroxyxanthones isolated from the Chinese herb, Tripterospermum lanceolatum (Hyata). Five tetrahydroxyxanthones (THXs) isolated from Tripterospermum lanceolatum (Hyata) have been shown to have a strong inhibitory effect on Moloney murine leukemia virus reverse transcriptase (Mo-MLV RT) activity when (rA)n-(dT)15 and (rC)n-(dT)12-18 were used as template-primers. 50% inhibitory concentrations of 1,3,5,6-THX, 2,3,6,7-THX 1,3,6,7-THX, 3,4,5,6-THX, and 3,4,6,7-THX were determined to be 0.15, 0.27, 0.58, 0.12, and 0.12 microM, respectively. Their effects were concentration-dependent, and the mode of inhibition was found to be by competitive inhibition with respect to template-primer. The tetrahydroxyl groups of THXs were shown to be important for their inhibitory activity. Acylation of THXs with various groups resulted in a moderate or strong decrease in their inhibitory activity."} {"id": "PMID:1280060", "title": "Bacterioplankton community structure and dynamics after large-scale release of nonindigenous bacteria as revealed by low-molecular-weight-RNA analysis.", "content": "A set of freshwater mesocosms (1.7 m3 each) was inoculated with large amounts of Escherichia coli, Pseudomonas putida, and their culture medium to substantially disturb the natural microbial community. To monitor microbial community dynamics, low-molecular-weight RNA (5S rRNA and tRNA) obtained directly from bacterioplankton was analyzed by using high-resolution electrophoresis. The introduced bacteria showed no significant effect on the community structure of the natural bacterial assemblage and its dynamics for 16 days. In contrast, the addition of culture medium resulted within 2 days in a reduction of community diversity due to dominance of a single 5S rRNA band from an indigenous bacterium. Partial sequencing of several 5S rRNAs demonstrated the molecular homogeneity of most of the abundant bands and enabled the identification of corresponding bacterial isolates and/or species. The dominating bacterium (around 54% of the total 5S rRNA) in the nutrient-amended mesocosms could be identified by partial sequencing as a member of the Aeromonas hydrophila complex. Another bloom of heterotrophic bacteria belonging to the Cytophaga johnsonae complex was detected in the nutrient-amended mesocosms after 13 days. The dominance of this C. johnsonae-like bacterium could even be seen in the environmental tRNAs of the bacterioplankton, where its specific tRNAs prevailed from day 13 onward. This event was also independent of the introduced nonindigenous bacteria because it occurred at the same time in all nutrient-amended mesocosms. By contrast, in the unamended experiments, a different small 5S rRNA could by observed from day 10 onward with less pronounced dominance.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Bacterioplankton community structure and dynamics after large-scale release of nonindigenous bacteria as revealed by low-molecular-weight-RNA analysis. A set of freshwater mesocosms (1.7 m3 each) was inoculated with large amounts of Escherichia coli, Pseudomonas putida, and their culture medium to substantially disturb the natural microbial community. To monitor microbial community dynamics, low-molecular-weight RNA (5S rRNA and tRNA) obtained directly from bacterioplankton was analyzed by using high-resolution electrophoresis. The introduced bacteria showed no significant effect on the community structure of the natural bacterial assemblage and its dynamics for 16 days. In contrast, the addition of culture medium resulted within 2 days in a reduction of community diversity due to dominance of a single 5S rRNA band from an indigenous bacterium. Partial sequencing of several 5S rRNAs demonstrated the molecular homogeneity of most of the abundant bands and enabled the identification of corresponding bacterial isolates and/or species. The dominating bacterium (around 54% of the total 5S rRNA) in the nutrient-amended mesocosms could be identified by partial sequencing as a member of the Aeromonas hydrophila complex. Another bloom of heterotrophic bacteria belonging to the Cytophaga johnsonae complex was detected in the nutrient-amended mesocosms after 13 days. The dominance of this C. johnsonae-like bacterium could even be seen in the environmental tRNAs of the bacterioplankton, where its specific tRNAs prevailed from day 13 onward. This event was also independent of the introduced nonindigenous bacteria because it occurred at the same time in all nutrient-amended mesocosms. By contrast, in the unamended experiments, a different small 5S rRNA could by observed from day 10 onward with less pronounced dominance.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280061", "title": "Differential amplification of rRNA genes by polymerase chain reaction.", "content": "The polymerase chain reaction (PCR) is used widely to recover rRNA genes from naturally occurring communities for analysis of population constituents. We have found that this method can result in differential amplification of different rRNA genes. In particular, rDNAs of extremely thermophilic archaebacteria often cannot be amplified by the usual PCR methods. The addition of 5% (wt/vol) acetamide to a PCR mixture containing both archaebacterial and yeast DNA templates minimized nonspecific annealing of the primers and prevented preferential amplification of the yeast small-subunit rRNA genes.", "contents": "Differential amplification of rRNA genes by polymerase chain reaction. The polymerase chain reaction (PCR) is used widely to recover rRNA genes from naturally occurring communities for analysis of population constituents. We have found that this method can result in differential amplification of different rRNA genes. In particular, rDNAs of extremely thermophilic archaebacteria often cannot be amplified by the usual PCR methods. The addition of 5% (wt/vol) acetamide to a PCR mixture containing both archaebacterial and yeast DNA templates minimized nonspecific annealing of the primers and prevented preferential amplification of the yeast small-subunit rRNA genes."} {"id": "PMID:1280062", "title": "Vibrio cholerae non-O1 isolated from ayu fish (Plecoglossus altivelis) in Japan.", "content": "A fish pathogen, Vibrio cholerae non-O1, was isolated from diseased ayu fish (Plecoglossus altivelis) collected from rivers in eight prefectural districts of Japan. This organism was found to have biochemical characteristics similar to those of V. cholerae non-O1, except that our isolates were negative for ornithine decarboxylase. Antiserum against an ayu isolate did not agglutinate with the majority of environmental V. cholerae non-O1 isolates, but a major O antigen was common among the ayu isolates. All strains were hemolytic to sheep erythrocytes, and oral administration of culture supernatants induced fluid accumulation in suckling mice. However, the crude toxin was not lethal to adult mice, and no cholera toxin-like enterotoxins were detected.", "contents": "Vibrio cholerae non-O1 isolated from ayu fish (Plecoglossus altivelis) in Japan. A fish pathogen, Vibrio cholerae non-O1, was isolated from diseased ayu fish (Plecoglossus altivelis) collected from rivers in eight prefectural districts of Japan. This organism was found to have biochemical characteristics similar to those of V. cholerae non-O1, except that our isolates were negative for ornithine decarboxylase. Antiserum against an ayu isolate did not agglutinate with the majority of environmental V. cholerae non-O1 isolates, but a major O antigen was common among the ayu isolates. All strains were hemolytic to sheep erythrocytes, and oral administration of culture supernatants induced fluid accumulation in suckling mice. However, the crude toxin was not lethal to adult mice, and no cholera toxin-like enterotoxins were detected."} {"id": "PMID:1280063", "title": "Multivalent ligand binding by serum mannose-binding protein.", "content": "The serum-type mannose-binding protein (MBP) is a defense molecule that has carbohydrate-dependent bactericidal effects. It shares with mammalian and chicken hepatic lectins similarity in the primary structure of the carbohydrate-recognition domain, as well as the ligand-binding mode: a high affinity (KD approximately nM) is generated by clustering of approximately 30 terminal target sugar residues on a macromolecule, such as bovine serum albumin, although the individual monosaccharides have low affinity (KD 0.1-1 mM). On the other hand, MBP does not manifest any significant affinity enhancement toward small, di- and trivalent ligands, in contrast to the hepatic lectins whose affinity toward divalent ligands of comparable structures increased from 100- to 1000-fold. Such differences may be explained on the basis of different subunit organization between the hepatic lectins and MBP.", "contents": "Multivalent ligand binding by serum mannose-binding protein. The serum-type mannose-binding protein (MBP) is a defense molecule that has carbohydrate-dependent bactericidal effects. It shares with mammalian and chicken hepatic lectins similarity in the primary structure of the carbohydrate-recognition domain, as well as the ligand-binding mode: a high affinity (KD approximately nM) is generated by clustering of approximately 30 terminal target sugar residues on a macromolecule, such as bovine serum albumin, although the individual monosaccharides have low affinity (KD 0.1-1 mM). On the other hand, MBP does not manifest any significant affinity enhancement toward small, di- and trivalent ligands, in contrast to the hepatic lectins whose affinity toward divalent ligands of comparable structures increased from 100- to 1000-fold. Such differences may be explained on the basis of different subunit organization between the hepatic lectins and MBP."} {"id": "PMID:1280064", "title": "The enhancement of Ca2+ efflux from sarcoplasmic reticulum vesicles by urea.", "content": "Urea, in nondenaturing concentrations, inhibited Ca2+ uptake by sarcoplasmic reticulum vesicles with no concomitant effect on ATP hydrolysis. This inhibition was antagonized by 5 mM oxalate and 20 mM orthophosphate. At concentrations of 0.2 to 1.0 M, urea induced an increase in the Ca2+ efflux from preloaded vesicles diluted in a medium at pH 7.0 containing 2 mM ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid, 0.1 mM orthophosphate, and 0.1 mM MgCl2. The urea-induced efflux was arrested by ligands of the (Ca(2+)-Mg2+) ATPase, namely, K+, Mg2+, Ca2+, and ADP, and by ruthenium red and the polyamines spermine, spermidine, and putrescine. In the case of polyamines a dissociation between the effect on the efflux and the net Ca2+ uptake was observed, as only the efflux could be blocked by the drugs. Glycine betaine, trimethylamine-N-oxide, and sucrose antagonized the effects of urea on both the net Ca2+ uptake and the rate of Ca2+ efflux.", "contents": "The enhancement of Ca2+ efflux from sarcoplasmic reticulum vesicles by urea. Urea, in nondenaturing concentrations, inhibited Ca2+ uptake by sarcoplasmic reticulum vesicles with no concomitant effect on ATP hydrolysis. This inhibition was antagonized by 5 mM oxalate and 20 mM orthophosphate. At concentrations of 0.2 to 1.0 M, urea induced an increase in the Ca2+ efflux from preloaded vesicles diluted in a medium at pH 7.0 containing 2 mM ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid, 0.1 mM orthophosphate, and 0.1 mM MgCl2. The urea-induced efflux was arrested by ligands of the (Ca(2+)-Mg2+) ATPase, namely, K+, Mg2+, Ca2+, and ADP, and by ruthenium red and the polyamines spermine, spermidine, and putrescine. In the case of polyamines a dissociation between the effect on the efflux and the net Ca2+ uptake was observed, as only the efflux could be blocked by the drugs. Glycine betaine, trimethylamine-N-oxide, and sucrose antagonized the effects of urea on both the net Ca2+ uptake and the rate of Ca2+ efflux."} {"id": "PMID:1280065", "title": "Analysis of plasmin binding and urokinase activation of plasminogen bound to the Heymann nephritis autoantigen, gp330.", "content": "Previously, we demonstrated that the Heymann nephritis autoantigen, gp330, can serve as a receptor site for plasminogen. This binding was not significantly inhibited by the lysine analogue epsilon-amino caproic acid (EACA), indicating that plasminogen binding was not just through lysine binding sites as suggested for other plasminogen binding sites. We now report that once plasminogen is bound to gp330, it can be converted to its active form of plasmin by urokinase. This conversion of plasminogen to plasmin proceeds at a faster rate when plasminogen is first prebound to gp330. Although there is a proportional increase in the Vmax of the urokinase-catalyzed reaction with increasing gp330 concentrations, no change in Km was observed. Once activated, plasmin remains bound to gp330 in an active state capable of cleaving the chromogenic tripeptide, S-2251. The binding of plasmin to gp330 did not significantly change its enzymatic activity; however, gp330 did have a stabilizing effect on plasmin activity at 37 degrees C. While bound to gp330, plasmin is protected from inactivation by its natural inhibitor alpha 2-antiplasmin. The binding of plasmin to gp330 as analyzed by ELISA was shown to be time dependent, reversible, saturable, and specific for gp330. Inhibition of binding of both plasminogen and plasmin to gp330 by benzamidine was similar, although EACA inhibited the binding of plasmin to gp330 slightly more than the binding of plasminogen to gp330. These results indicate that the binding of plasminogen to gp330 serves as an effective means of increasing the rate of plasmin production on the glomerular and tubular epithelial cell surface while protecting the active plasmin from natural inhibitors.", "contents": "Analysis of plasmin binding and urokinase activation of plasminogen bound to the Heymann nephritis autoantigen, gp330. Previously, we demonstrated that the Heymann nephritis autoantigen, gp330, can serve as a receptor site for plasminogen. This binding was not significantly inhibited by the lysine analogue epsilon-amino caproic acid (EACA), indicating that plasminogen binding was not just through lysine binding sites as suggested for other plasminogen binding sites. We now report that once plasminogen is bound to gp330, it can be converted to its active form of plasmin by urokinase. This conversion of plasminogen to plasmin proceeds at a faster rate when plasminogen is first prebound to gp330. Although there is a proportional increase in the Vmax of the urokinase-catalyzed reaction with increasing gp330 concentrations, no change in Km was observed. Once activated, plasmin remains bound to gp330 in an active state capable of cleaving the chromogenic tripeptide, S-2251. The binding of plasmin to gp330 did not significantly change its enzymatic activity; however, gp330 did have a stabilizing effect on plasmin activity at 37 degrees C. While bound to gp330, plasmin is protected from inactivation by its natural inhibitor alpha 2-antiplasmin. The binding of plasmin to gp330 as analyzed by ELISA was shown to be time dependent, reversible, saturable, and specific for gp330. Inhibition of binding of both plasminogen and plasmin to gp330 by benzamidine was similar, although EACA inhibited the binding of plasmin to gp330 slightly more than the binding of plasminogen to gp330. These results indicate that the binding of plasminogen to gp330 serves as an effective means of increasing the rate of plasmin production on the glomerular and tubular epithelial cell surface while protecting the active plasmin from natural inhibitors."} {"id": "PMID:1280066", "title": "Characterization of lipid A from Pseudomonas aeruginosa O-antigenic B band lipopolysaccharide by 1D and 2D NMR and mass spectral analysis.", "content": "The Lipid A from the lipopolysaccharide of Pseudomonas aeruginosa was examined by high-field nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The backbone structure and the position of phosphate substituents were unambiguously established by one- and two-dimensional 1H, 13C, and 31P NMR techniques on a de-O-acylated Lipid A sample. The Lipid A has a beta-(1,6)-glucosamine disaccharide structure which is substituted by phosphomonoesters through glycosidic bonds at C-1 and at C-4'. The configuration of the glycosidically linked phosphate at position C-1 was identified as alpha which is the same as that of Enterobacterial Lipid A. Chemical analysis revealed that the Lipid A contained 2-hydroxydodecanoic, 3-hydroxydodecanoic, dodecanoic, 3-hydroxydecanoic, and hexadecanoic acids in the approximate molar ratios 2.2:2.0:0.2:0.8:0.4. From 1H NMR and fast atom bombardment (FAB) mass spectrometry on the de-O-acylated Lipid A, it was established that both glucosamine residues were N-acylated by 3-hydroxydodecanoic acid. The identity and positions of the ester bound fatty acids in the intact Lipid A were investigated by negative ion FAB-MS. In addition to the hexaacyl and pentaacyl Lipid A species, a tetraacyl species was identified. Heterogeneity due to hydroxylated and nonhydroxylated dodecanoic acid esters could be uniquely localized to the nonreducing beta-glucosamine residue from the fragmentation pattern observed in the negative ion FAB-MS. The complete structure of the Lipid A from P. aeruginosa will be useful in understanding the determinants responsible for the endotoxin activity of this molecule.", "contents": "Characterization of lipid A from Pseudomonas aeruginosa O-antigenic B band lipopolysaccharide by 1D and 2D NMR and mass spectral analysis. The Lipid A from the lipopolysaccharide of Pseudomonas aeruginosa was examined by high-field nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS). The backbone structure and the position of phosphate substituents were unambiguously established by one- and two-dimensional 1H, 13C, and 31P NMR techniques on a de-O-acylated Lipid A sample. The Lipid A has a beta-(1,6)-glucosamine disaccharide structure which is substituted by phosphomonoesters through glycosidic bonds at C-1 and at C-4'. The configuration of the glycosidically linked phosphate at position C-1 was identified as alpha which is the same as that of Enterobacterial Lipid A. Chemical analysis revealed that the Lipid A contained 2-hydroxydodecanoic, 3-hydroxydodecanoic, dodecanoic, 3-hydroxydecanoic, and hexadecanoic acids in the approximate molar ratios 2.2:2.0:0.2:0.8:0.4. From 1H NMR and fast atom bombardment (FAB) mass spectrometry on the de-O-acylated Lipid A, it was established that both glucosamine residues were N-acylated by 3-hydroxydodecanoic acid. The identity and positions of the ester bound fatty acids in the intact Lipid A were investigated by negative ion FAB-MS. In addition to the hexaacyl and pentaacyl Lipid A species, a tetraacyl species was identified. Heterogeneity due to hydroxylated and nonhydroxylated dodecanoic acid esters could be uniquely localized to the nonreducing beta-glucosamine residue from the fragmentation pattern observed in the negative ion FAB-MS. The complete structure of the Lipid A from P. aeruginosa will be useful in understanding the determinants responsible for the endotoxin activity of this molecule."} {"id": "PMID:1280067", "title": "[Short-term incubation study on inhibitory effect of chemohyperthermia against hormone-independent human prostatic carcinoma cell line (PC-3)].", "content": "The sensitivity of a hormone-independent human prostatic carcinoma cell line (PC-3) to chemohyperthermia was evaluated in vitro. The anticancer drugs used here were vincristine sulfate (VCR), peplomycin sulfate (PLM) and cis-diamminedichloroplatinum (CDDP). To evaluate cytotoxicity in short-term treatment, an inhibitory test on cell survival was more useful than a test on cell proliferation. With the inhibitory test on cell survival, the relationship of the administration method was examined to obtain better cell cytotoxicity, i.e., the cells were exposed to 1) the drug and heat at 43 degrees C simultaneously, 2) the drug followed by heat, or 3) heat followed by the drug. The combined treatment with drug and heat simultaneously produced more pronounced cytotoxicity than the treatment with heat followed by drug administration. The combined effect did not result from exposure to the drug followed by heat. Of the three drugs, the action of VCR and CDDP was potentiated with heat, but PLM was not.", "contents": "[Short-term incubation study on inhibitory effect of chemohyperthermia against hormone-independent human prostatic carcinoma cell line (PC-3)]. The sensitivity of a hormone-independent human prostatic carcinoma cell line (PC-3) to chemohyperthermia was evaluated in vitro. The anticancer drugs used here were vincristine sulfate (VCR), peplomycin sulfate (PLM) and cis-diamminedichloroplatinum (CDDP). To evaluate cytotoxicity in short-term treatment, an inhibitory test on cell survival was more useful than a test on cell proliferation. With the inhibitory test on cell survival, the relationship of the administration method was examined to obtain better cell cytotoxicity, i.e., the cells were exposed to 1) the drug and heat at 43 degrees C simultaneously, 2) the drug followed by heat, or 3) heat followed by the drug. The combined treatment with drug and heat simultaneously produced more pronounced cytotoxicity than the treatment with heat followed by drug administration. The combined effect did not result from exposure to the drug followed by heat. Of the three drugs, the action of VCR and CDDP was potentiated with heat, but PLM was not."} {"id": "PMID:1280068", "title": "Distribution of Merkel cells in acute UVB erythema.", "content": "Merkel cells (MC) were identified immunohistochemically using antibodies specific for cytokeratin (CK) 20 within human epidermis 12 to 72 h after exposure to UVB (4 MED). 12 h after exposure all MC were normally localized within the epidermal basal layer. However, 24 h after exposure 4% of the MC were detected suprabasally, the remaining 96% still being situated in the basal layer. Surprisingly, at 48 h and 72 h more than 50% had lost contact with the basal membrane. The MC of hair follicles did not show any obvious changes. These results argue, in the context of acute epidermal UV damage, for an abnormal turnover in dermatitis.", "contents": "Distribution of Merkel cells in acute UVB erythema. Merkel cells (MC) were identified immunohistochemically using antibodies specific for cytokeratin (CK) 20 within human epidermis 12 to 72 h after exposure to UVB (4 MED). 12 h after exposure all MC were normally localized within the epidermal basal layer. However, 24 h after exposure 4% of the MC were detected suprabasally, the remaining 96% still being situated in the basal layer. Surprisingly, at 48 h and 72 h more than 50% had lost contact with the basal membrane. The MC of hair follicles did not show any obvious changes. These results argue, in the context of acute epidermal UV damage, for an abnormal turnover in dermatitis."} {"id": "PMID:1280070", "title": "Fate and effects of the insecticide Dursban 4E in indoor Elodea-dominated and macrophyte-free freshwater model ecosystems: II. Secondary effects on community structure.", "content": "Secondary effects of a single dose of the insecticide Dursban 4E (active ingredient chlorpyrifos) were studied in indoor experimental freshwater ecosystems intended to mimic drainage ditches. Two experiments were performed, one in which all model ecosystems were dominated by the macrophyte Elodea muttallii, and one using systems devoid of macrophytes. In the Elodea-dominated and macrophyte-free model ecosystems, populations of primary producers, herbivores, carnivores and detritivores were indirectly affected via the loss of populations of Arthropoda as a direct result of insecticide application. However, the taxa in which secondary effects were observed differed considerably between these two types of model ecosystem. In macrophyte-dominated systems secondary effects were observed on populations of periphytic algae, the macrophyte Elodea nuttallii, the gastropod Bithynia tentaculata, Turbellaria, and sediment dwelling Oligochaeta. In open water systems it were populations of phytoplankton, the rotators Polyarthra and Asplanchna, bivalves (Sphaeriidae), Hirudinea, sediment dwelling Oligochaeta, and that of the isopod Proasellus coxalis in which secondary effects were observed. In aquatic ecosystems the presence or absence of a well-developed macrophyte vegetation may be a very important characteristic that determines the nature and route of secondary effects induced by pesticides. The differences in secondary effects observed between Elodea-dominated and macrophyte-free model ecosystems indicate that the system's structure and trophic dynamics should be taken into account when predicting ecological effects.", "contents": "Fate and effects of the insecticide Dursban 4E in indoor Elodea-dominated and macrophyte-free freshwater model ecosystems: II. Secondary effects on community structure. Secondary effects of a single dose of the insecticide Dursban 4E (active ingredient chlorpyrifos) were studied in indoor experimental freshwater ecosystems intended to mimic drainage ditches. Two experiments were performed, one in which all model ecosystems were dominated by the macrophyte Elodea muttallii, and one using systems devoid of macrophytes. In the Elodea-dominated and macrophyte-free model ecosystems, populations of primary producers, herbivores, carnivores and detritivores were indirectly affected via the loss of populations of Arthropoda as a direct result of insecticide application. However, the taxa in which secondary effects were observed differed considerably between these two types of model ecosystem. In macrophyte-dominated systems secondary effects were observed on populations of periphytic algae, the macrophyte Elodea nuttallii, the gastropod Bithynia tentaculata, Turbellaria, and sediment dwelling Oligochaeta. In open water systems it were populations of phytoplankton, the rotators Polyarthra and Asplanchna, bivalves (Sphaeriidae), Hirudinea, sediment dwelling Oligochaeta, and that of the isopod Proasellus coxalis in which secondary effects were observed. In aquatic ecosystems the presence or absence of a well-developed macrophyte vegetation may be a very important characteristic that determines the nature and route of secondary effects induced by pesticides. The differences in secondary effects observed between Elodea-dominated and macrophyte-free model ecosystems indicate that the system's structure and trophic dynamics should be taken into account when predicting ecological effects."} {"id": "PMID:1280071", "title": "[Controversy regarding the therapeutic management of stage B2, C and D1 adenocarcinoma].", "content": "In Spain most prostate cancers are detected once they have already disseminated. The tumor, however, is localized to the prostate gland for a period of time before spreading to other structures. It is therefore important to underscore the value of early diagnosis. And if we take into account that the complications of radical prostatectomy have diminished and life expectancy of the general population has increased, undoubtedly an increased number of patients can benefit from surgery. Radical prostatectomy combined with pre and postoperative hormone therapy may enhance the quality of life of some patients with tumors extending beyond the capsule (clinical stage B2-C), including those with microscopic dissemination to the regional lymph nodes. Surgery should aim at complete removal of the pelvic tumor. Although a statistical relationship exists between blood PSA levels and tumor grade and size, elevation of PSA levels is not sufficient to predict malignancy or tumor spread and is of little value in predicting response to hormone therapy.", "contents": "[Controversy regarding the therapeutic management of stage B2, C and D1 adenocarcinoma]. In Spain most prostate cancers are detected once they have already disseminated. The tumor, however, is localized to the prostate gland for a period of time before spreading to other structures. It is therefore important to underscore the value of early diagnosis. And if we take into account that the complications of radical prostatectomy have diminished and life expectancy of the general population has increased, undoubtedly an increased number of patients can benefit from surgery. Radical prostatectomy combined with pre and postoperative hormone therapy may enhance the quality of life of some patients with tumors extending beyond the capsule (clinical stage B2-C), including those with microscopic dissemination to the regional lymph nodes. Surgery should aim at complete removal of the pelvic tumor. Although a statistical relationship exists between blood PSA levels and tumor grade and size, elevation of PSA levels is not sufficient to predict malignancy or tumor spread and is of little value in predicting response to hormone therapy."} {"id": "PMID:1280073", "title": "Treatment of severe thrombocytopenia in systemic lupus erythematosus with intravenous gammaglobulin.", "content": "Three patients with lupus with severe auto-immune thrombocytopenia were treated with high doses of intravenous gammaglobulin. In the patient with active disease a prolonged but partial response with respect to platelet counts was observed. In the two other patients who had no disease activity other than thrombocytopenia at the time of intravenous gammaglobulin treatment a minor (and only transient) increase in platelet counts was seen after treatment. No change in the state of disease activity nor in the levels of antinuclear antibodies, circulating immune complexes, nor complement C3/4 was observed in these three patients after treatment with intravenous gammaglobulin.", "contents": "Treatment of severe thrombocytopenia in systemic lupus erythematosus with intravenous gammaglobulin. Three patients with lupus with severe auto-immune thrombocytopenia were treated with high doses of intravenous gammaglobulin. In the patient with active disease a prolonged but partial response with respect to platelet counts was observed. In the two other patients who had no disease activity other than thrombocytopenia at the time of intravenous gammaglobulin treatment a minor (and only transient) increase in platelet counts was seen after treatment. No change in the state of disease activity nor in the levels of antinuclear antibodies, circulating immune complexes, nor complement C3/4 was observed in these three patients after treatment with intravenous gammaglobulin."} {"id": "PMID:1280074", "title": "An appraisal of pediatric liver transplantation from living relatives. Initial clinical experiences in 20 pediatric liver transplantations from living relatives as donors.", "content": "The authors performed 20 liver transplantations from living related donors between June 1990 and July 1991. The 20 pediatric patients (14 biliary atresia, two Budd-Chiari syndrome, one liver cirrhosis after hepatitis C viral infection (HCV hepatitis), 1 progressive intrahepatic cholestasis, 1 liver cirrhosis, 1 protoporphyria) were transplanted with 11 left lobes, eight left lateral segments, and one right lobe. The choice of donors was restricted to the parents of the recipients. The immunosuppressive treatment consisted of FK 506 and steroids. Seventeen recipients are alive, 15 of whom are well and at home. Two recipients, who underwent emergency transplantation, died of postoperative complications. Another recipient died of accidental asphyxia at 6 months after the transplantation. All 20 donors had uneventful postoperative courses and were able to resume their normal social lives. The arterial ketone body ratio (AKBR) increased to above 1.0 within 2 days after the transplantation in all cases. Relatively mild rejection episodes were encountered in only two cases transplanted with ABO-compatible grafts, and these were treated successfully with steroids and FK 506.", "contents": "An appraisal of pediatric liver transplantation from living relatives. Initial clinical experiences in 20 pediatric liver transplantations from living relatives as donors. The authors performed 20 liver transplantations from living related donors between June 1990 and July 1991. The 20 pediatric patients (14 biliary atresia, two Budd-Chiari syndrome, one liver cirrhosis after hepatitis C viral infection (HCV hepatitis), 1 progressive intrahepatic cholestasis, 1 liver cirrhosis, 1 protoporphyria) were transplanted with 11 left lobes, eight left lateral segments, and one right lobe. The choice of donors was restricted to the parents of the recipients. The immunosuppressive treatment consisted of FK 506 and steroids. Seventeen recipients are alive, 15 of whom are well and at home. Two recipients, who underwent emergency transplantation, died of postoperative complications. Another recipient died of accidental asphyxia at 6 months after the transplantation. All 20 donors had uneventful postoperative courses and were able to resume their normal social lives. The arterial ketone body ratio (AKBR) increased to above 1.0 within 2 days after the transplantation in all cases. Relatively mild rejection episodes were encountered in only two cases transplanted with ABO-compatible grafts, and these were treated successfully with steroids and FK 506."} {"id": "PMID:1280075", "title": "Hepatitis C virus seroprevalence in the developmentally disabled.", "content": "Hepatitis C virus (HCV) is the principal cause of nonenteric non-A, non-B hepatitis worldwide. While it has been well documented that people with developmental disabilities are at an increased risk for infections with hepatitis B virus, little is known of the prevalence of HCV infection among this population. Serum samples obtained from 113 evaluable outpatients with developmental disabilities at one center in suburban New York City (NY) were tested for antibodies to HCV and hepatitis B core antibody. None of the 113 samples tested positive for HCV antibody by enzyme-linked immunosorbent assay, whereas 24 (21%) showed serologic evidence of past hepatitis B virus infection on the basis of hepatitis B core antibody positivity. Three (2.7%) were also positive for hepatitis B surface antigen. In contrast to hepatitis B virus, HCV infection is uncommon among outpatients with developmental disabilities in suburban New York City. Further testing for HCV is indicated to determine if these results can be generalized to individuals within institutions, or to individuals in other geographic locations.", "contents": "Hepatitis C virus seroprevalence in the developmentally disabled. Hepatitis C virus (HCV) is the principal cause of nonenteric non-A, non-B hepatitis worldwide. While it has been well documented that people with developmental disabilities are at an increased risk for infections with hepatitis B virus, little is known of the prevalence of HCV infection among this population. Serum samples obtained from 113 evaluable outpatients with developmental disabilities at one center in suburban New York City (NY) were tested for antibodies to HCV and hepatitis B core antibody. None of the 113 samples tested positive for HCV antibody by enzyme-linked immunosorbent assay, whereas 24 (21%) showed serologic evidence of past hepatitis B virus infection on the basis of hepatitis B core antibody positivity. Three (2.7%) were also positive for hepatitis B surface antigen. In contrast to hepatitis B virus, HCV infection is uncommon among outpatients with developmental disabilities in suburban New York City. Further testing for HCV is indicated to determine if these results can be generalized to individuals within institutions, or to individuals in other geographic locations."} {"id": "PMID:1280076", "title": "Effect of short-termed pancreatico-biliary duct obstruction on lysosomal enzyme in rats: protective effect of a potent new protease inhibitor, E-3123.", "content": "To investigate the mechanism by which the pancreatic acinar cells are injured in animals with an obstructed common channel, we measured the amount of lysosomal enzymes and of amylase in the pancreatico-biliary juice in rats with pancreatico-biliary duct obstruction (PBDO). We tested the protective effect of a new potent synthetic protease inhibitor, E3123 (4-guanidinobenzoate methanesulfonate), on the exocrine pancreas in this model of PBDO and secretin infusion. Blockage of PBD for 4 hours and secretin (0.2 CU/kg.hr) infusion caused a significant rise in portal serum amylase and cathepsin B levels, pancreatic water content, and pancreatic amylase content, as well as redistribution of cathepsin B in acinar cells. These changes tended to continue for 12 hours after the removal of PBDO and disappeared at 24 hours. All the changes induced by PBDO with secretin infusion were no longer observed at 48 hours. The administration of 5 mg/kg.hr of E3123 during PBDO markedly attenuated all the parameters examined in this study. Thus, it had a significant protective effect on acinar cells in this model. E3123 in a dose of 2 mg/kg.hr had a partial, but significant, protective effect. These results indicate the possible usefulness of E3123 in the treatment of pancreatic duct obstructed pancreatitis.", "contents": "Effect of short-termed pancreatico-biliary duct obstruction on lysosomal enzyme in rats: protective effect of a potent new protease inhibitor, E-3123. To investigate the mechanism by which the pancreatic acinar cells are injured in animals with an obstructed common channel, we measured the amount of lysosomal enzymes and of amylase in the pancreatico-biliary juice in rats with pancreatico-biliary duct obstruction (PBDO). We tested the protective effect of a new potent synthetic protease inhibitor, E3123 (4-guanidinobenzoate methanesulfonate), on the exocrine pancreas in this model of PBDO and secretin infusion. Blockage of PBD for 4 hours and secretin (0.2 CU/kg.hr) infusion caused a significant rise in portal serum amylase and cathepsin B levels, pancreatic water content, and pancreatic amylase content, as well as redistribution of cathepsin B in acinar cells. These changes tended to continue for 12 hours after the removal of PBDO and disappeared at 24 hours. All the changes induced by PBDO with secretin infusion were no longer observed at 48 hours. The administration of 5 mg/kg.hr of E3123 during PBDO markedly attenuated all the parameters examined in this study. Thus, it had a significant protective effect on acinar cells in this model. E3123 in a dose of 2 mg/kg.hr had a partial, but significant, protective effect. These results indicate the possible usefulness of E3123 in the treatment of pancreatic duct obstructed pancreatitis."} {"id": "PMID:1280077", "title": "Proliferating cell nuclear antigen. A marker for cell proliferation in autopsy tissues.", "content": "Antibodies to the proliferating cell nuclear antigen allow identification of proliferating cells in fresh tissue specimens using routine immunocytochemical methods. However, the use of such proliferation markers has not been verified for autopsy-derived tissue specimens, in which there is often a significant delay between the time of death and tissue specimen fixation. To assess the reliability of anti-proliferating cell nuclear antigen antibodies to identify proliferating cells in autopsy tissue specimens, an autopsy simulation was performed using fresh monkey and rat tissue specimens. These tissue specimens were kept at room temperature for predetermined numbers of hours before fixation. The proliferation specific staining was most reliable for tissue specimens obtained within 6 hours of death. There was reliable staining of proliferating regions up to 12 hours, although sensitivity was decreased. The only exception was skin, which was able to withstand much longer periods. Quantitative data from monkey spleen white-pulp regions showed 63% of the cells to stain for proliferating cell nuclear antigen when fixed immediately; this decreased to 29% of the cells after 12 hours and only 19% by 18 hours of postmortem simulation. Representative tissue specimens obtained from human autopsy material revealed similar postmortem staining patterns. Rapid procurement and fixation of tissue specimens and the use of control tissue specimens derived from the same autopsy material (eg, lymph node tissue) are recommended. These studies do suggest that anti-proliferating cell nuclear antigen antibodies can be used to identify proliferating cells in human autopsy tissue specimens obtained within approximately 12 hours of death, with some compromise in overall sensitivity.", "contents": "Proliferating cell nuclear antigen. A marker for cell proliferation in autopsy tissues. Antibodies to the proliferating cell nuclear antigen allow identification of proliferating cells in fresh tissue specimens using routine immunocytochemical methods. However, the use of such proliferation markers has not been verified for autopsy-derived tissue specimens, in which there is often a significant delay between the time of death and tissue specimen fixation. To assess the reliability of anti-proliferating cell nuclear antigen antibodies to identify proliferating cells in autopsy tissue specimens, an autopsy simulation was performed using fresh monkey and rat tissue specimens. These tissue specimens were kept at room temperature for predetermined numbers of hours before fixation. The proliferation specific staining was most reliable for tissue specimens obtained within 6 hours of death. There was reliable staining of proliferating regions up to 12 hours, although sensitivity was decreased. The only exception was skin, which was able to withstand much longer periods. Quantitative data from monkey spleen white-pulp regions showed 63% of the cells to stain for proliferating cell nuclear antigen when fixed immediately; this decreased to 29% of the cells after 12 hours and only 19% by 18 hours of postmortem simulation. Representative tissue specimens obtained from human autopsy material revealed similar postmortem staining patterns. Rapid procurement and fixation of tissue specimens and the use of control tissue specimens derived from the same autopsy material (eg, lymph node tissue) are recommended. These studies do suggest that anti-proliferating cell nuclear antigen antibodies can be used to identify proliferating cells in human autopsy tissue specimens obtained within approximately 12 hours of death, with some compromise in overall sensitivity."} {"id": "PMID:1280078", "title": "Development of innumerable neuroendocrine tumorlets in pulmonary lobe scarred by intralobar sequestration. Immunohistochemical and ultrastructural study of an unusual case.", "content": "We describe the microscopic, histochemical, immunohistochemical, and ultrastructural features of hundreds of neuroendocrine tumorlets occurring within a pulmonary lobe severely scarred by intralobar sequestration in a nonsmoking 49-year-old white man. To our knowledge, there have thus far been no descriptions or detailed analyses of neuroendocrine tumorlets arising within a pulmonary sequestration. The neuroendocrine tumorlets appeared in the form of minute aggregates--mostly microscopic, up to a maximum of 0.3 cm in greatest diameter--of small round and short spindle-shaped cells. They were organized in compact nests of fascicles and were supplied with round or elongated euchromatic nuclei and scant weakly eosinophilic cytoplasm. The neuroendocrine tumorlets were clustered around diseased bronchioles or embedded in a fibrotic pulmonary parenchyma with a distinctive infiltrative appearance. Sometimes they lay near an artery channel without an identifiable bronchiole or herniated into distal airways. Most of the neuroendocrine tumorlets were strongly argyrophilic on Grimelius staining. Immunohistochemically, there was reactivity for markers of epithelial and neuroendocrine differentiation together with evidence of orthotopic production of calcitonin, serotonin, and gastrin-releasing peptide and ectopic production of vasoactive intestinal peptide. Ultrastructurally, most of the neuroendocrine cells showed 100- to 120-nm dense-core membrane-bound secretory granules; mucus secretory cells were also present. We prefer the term neuroendocrine tumorlets over the generally used term carcinoid tumorlets, because the nature of these lesions is undefined and the relationship with neuroendocrine pulmonary neoplasms is not yet established.", "contents": "Development of innumerable neuroendocrine tumorlets in pulmonary lobe scarred by intralobar sequestration. Immunohistochemical and ultrastructural study of an unusual case. We describe the microscopic, histochemical, immunohistochemical, and ultrastructural features of hundreds of neuroendocrine tumorlets occurring within a pulmonary lobe severely scarred by intralobar sequestration in a nonsmoking 49-year-old white man. To our knowledge, there have thus far been no descriptions or detailed analyses of neuroendocrine tumorlets arising within a pulmonary sequestration. The neuroendocrine tumorlets appeared in the form of minute aggregates--mostly microscopic, up to a maximum of 0.3 cm in greatest diameter--of small round and short spindle-shaped cells. They were organized in compact nests of fascicles and were supplied with round or elongated euchromatic nuclei and scant weakly eosinophilic cytoplasm. The neuroendocrine tumorlets were clustered around diseased bronchioles or embedded in a fibrotic pulmonary parenchyma with a distinctive infiltrative appearance. Sometimes they lay near an artery channel without an identifiable bronchiole or herniated into distal airways. Most of the neuroendocrine tumorlets were strongly argyrophilic on Grimelius staining. Immunohistochemically, there was reactivity for markers of epithelial and neuroendocrine differentiation together with evidence of orthotopic production of calcitonin, serotonin, and gastrin-releasing peptide and ectopic production of vasoactive intestinal peptide. Ultrastructurally, most of the neuroendocrine cells showed 100- to 120-nm dense-core membrane-bound secretory granules; mucus secretory cells were also present. We prefer the term neuroendocrine tumorlets over the generally used term carcinoid tumorlets, because the nature of these lesions is undefined and the relationship with neuroendocrine pulmonary neoplasms is not yet established."} {"id": "PMID:1280079", "title": "Glomerular calcinosis in sarcoidosis.", "content": "Glomerular lesions secondary to calcium deposition in sarcoidosis have not been previously described, to our knowledge. Five renal biopsy specimens from four patients with sarcoidosis were studied by light, electron, and immunofluorescence microscopy. In addition to interstitial granulomatous nephritis and nephrocalcinosis, which were seen in all cases, segmental glomerular lesions characterized by marked thickening and wrinkling of the glomerular capillary walls and basophilic appearance of the altered basement membranes were present in three of the cases. Electron microscopic examination of the lesions revealed dramatic alteration of the glomerular ultrastructure. Numerous single and coalescent calcific microspherules were present within the basement membrane, the paramesangial zone, and the mesangium. The findings of immunofluorescence were noncontributory. The structural alterations caused by calcinosis of the glomerulus may be responsible for some of the frequent renal function abnormalities seen in sarcoidosis.", "contents": "Glomerular calcinosis in sarcoidosis. Glomerular lesions secondary to calcium deposition in sarcoidosis have not been previously described, to our knowledge. Five renal biopsy specimens from four patients with sarcoidosis were studied by light, electron, and immunofluorescence microscopy. In addition to interstitial granulomatous nephritis and nephrocalcinosis, which were seen in all cases, segmental glomerular lesions characterized by marked thickening and wrinkling of the glomerular capillary walls and basophilic appearance of the altered basement membranes were present in three of the cases. Electron microscopic examination of the lesions revealed dramatic alteration of the glomerular ultrastructure. Numerous single and coalescent calcific microspherules were present within the basement membrane, the paramesangial zone, and the mesangium. The findings of immunofluorescence were noncontributory. The structural alterations caused by calcinosis of the glomerulus may be responsible for some of the frequent renal function abnormalities seen in sarcoidosis."} {"id": "PMID:1280080", "title": "Staging laparoscopic pelvic lymph node dissection. Experience and indications.", "content": "Laparoscopic pelvic lymph node dissection has proven to be a reliable, less-invasive method for staging prostate cancer. Presently, no clear indications for its performance prior to radical retropubic prostatectomy are available. With the purpose of identifying clinical parameters by which to better select patients who would benefit from laparoscopic pelvic lymph node dissection, we chose to perform the procedure only in patients considered at high risk for nodal metastasis: clinical stages B2 or C, poorly differentiated tumors, and/or a serum prostatic-specific antigen level of more than 20 ng/dL. We compared the results with those of patients not meeting such parameters. Of 80 men receiving treatment for clinically localized disease, 30 (38%) fulfilled one or more of the criteria. When considering the individual clinical parameters, clinical stage was predictive of nodal involvement in five (26%) of 19 patients, grade was predictive in three (37.5%) of eight patients, and prostatic-specific antigen level was predictive in six (40%) of 15 patients. Statistical analysis confirmed that the prostatic-specific antigen level was the single best predictor of nodal involvement. However, better predictive values were obtained when the different criteria were combined. Nodal involvement was predicted most consistently by a combination of clinical stage and prostatic-specific antigen level.", "contents": "Staging laparoscopic pelvic lymph node dissection. Experience and indications. Laparoscopic pelvic lymph node dissection has proven to be a reliable, less-invasive method for staging prostate cancer. Presently, no clear indications for its performance prior to radical retropubic prostatectomy are available. With the purpose of identifying clinical parameters by which to better select patients who would benefit from laparoscopic pelvic lymph node dissection, we chose to perform the procedure only in patients considered at high risk for nodal metastasis: clinical stages B2 or C, poorly differentiated tumors, and/or a serum prostatic-specific antigen level of more than 20 ng/dL. We compared the results with those of patients not meeting such parameters. Of 80 men receiving treatment for clinically localized disease, 30 (38%) fulfilled one or more of the criteria. When considering the individual clinical parameters, clinical stage was predictive of nodal involvement in five (26%) of 19 patients, grade was predictive in three (37.5%) of eight patients, and prostatic-specific antigen level was predictive in six (40%) of 15 patients. Statistical analysis confirmed that the prostatic-specific antigen level was the single best predictor of nodal involvement. However, better predictive values were obtained when the different criteria were combined. Nodal involvement was predicted most consistently by a combination of clinical stage and prostatic-specific antigen level."} {"id": "PMID:1280081", "title": "How and where does acute pancreatitis begin?", "content": "Circumstantial evidence suggests that gallstone-induced pancreatitis is triggered by obstruction of the pancreatic duct. In this report I will review the results of studies conducted during the last decade that have employed the diet-induced, secretagogue-induced, and duct obstruction-induced models of experimental pancreatitis to investigate the early events that lead to the development of acute pancreatitis. In each of these models, digestive enzyme zymogens and the lysosomal hydrolase cathepsin B were found to become colocalized. These observations have led to the hypothesis that intra-acinar cell activation of digestive enzyme zymogens by lysosomal hydrolases may be an important critical event in the development of acute pancreatitis. Recent morphologic studies evaluating the initial 24 hours after ligation of the opossum pancreatic duct indicate that the earliest lesions in this model of hemorrhagic pancreatitis occur in acinar cells.", "contents": "How and where does acute pancreatitis begin? Circumstantial evidence suggests that gallstone-induced pancreatitis is triggered by obstruction of the pancreatic duct. In this report I will review the results of studies conducted during the last decade that have employed the diet-induced, secretagogue-induced, and duct obstruction-induced models of experimental pancreatitis to investigate the early events that lead to the development of acute pancreatitis. In each of these models, digestive enzyme zymogens and the lysosomal hydrolase cathepsin B were found to become colocalized. These observations have led to the hypothesis that intra-acinar cell activation of digestive enzyme zymogens by lysosomal hydrolases may be an important critical event in the development of acute pancreatitis. Recent morphologic studies evaluating the initial 24 hours after ligation of the opossum pancreatic duct indicate that the earliest lesions in this model of hemorrhagic pancreatitis occur in acinar cells."} {"id": "PMID:1280082", "title": "Renal effects of in utero exposure to mercuric chloride in rats.", "content": "The transplacental nephrotoxicity of mercuric chloride has been studied in female Sprague-Dawley rats. Mercuric chloride was injected s.c. to rats at the dose of 1 mg/kg during the last 8 gestational days or the whole pregnancy. Both mothers and newborns developed a transient renal dysfunction resulting in an increased urinary excretion of beta 2-microglobulin and albumin. In mothers and their female offspring, these effects were completely reversible and did not influence the subsequent evolution of the renal function. In the male offspring, however, transitory changes in protein excretion were again observed a few months later, concomitantly with an enhanced accumulation of alpha 2u-globulin in the kidney. The transfer of mercury from maternal to fetal tissues was very small. The kidney concentrations of mercury in newborns were more than 300 times lower than in mothers. The barrier role of the placenta is not sufficient to prevent the occurrence of renal effects in the offspring of rats treated with inorganic mercury during pregnancy.", "contents": "Renal effects of in utero exposure to mercuric chloride in rats. The transplacental nephrotoxicity of mercuric chloride has been studied in female Sprague-Dawley rats. Mercuric chloride was injected s.c. to rats at the dose of 1 mg/kg during the last 8 gestational days or the whole pregnancy. Both mothers and newborns developed a transient renal dysfunction resulting in an increased urinary excretion of beta 2-microglobulin and albumin. In mothers and their female offspring, these effects were completely reversible and did not influence the subsequent evolution of the renal function. In the male offspring, however, transitory changes in protein excretion were again observed a few months later, concomitantly with an enhanced accumulation of alpha 2u-globulin in the kidney. The transfer of mercury from maternal to fetal tissues was very small. The kidney concentrations of mercury in newborns were more than 300 times lower than in mothers. The barrier role of the placenta is not sufficient to prevent the occurrence of renal effects in the offspring of rats treated with inorganic mercury during pregnancy."} {"id": "PMID:1280083", "title": "Effect of triphenyltin chloride on the release of histamine from mast cells.", "content": "The effects of triphenyltin chloride (TPTC) on the release of histamine from rat and mouse mast cells in vitro and in vivo were investigated. The results obtained are summarized as follows: (a) At doses between 1 and 3 mg/kg, TPTC inhibited the dye leakage due to passive cutaneous anaphylaxis mediated by IgE antibody in mouse ear. At the same doses, TPTC inhibited the swelling due to reversed cutaneous anaphylaxis mediated by IgG antibody in rat. However, TPTC did not affect dye leakage due to histamine, serotonin, and LTC4 in rat skin; (b) Histamine release by antigen and IgE antibody in rat peritoneal cavity was inhibited by the administration of TPTC at doses between 0.3 and 3 mg/kg; (c) Histamine release by calcium ionophore A 23187 from purified rat peritoneal mast cells in vitro was inhibited by TPTC at concentrations between 10(-7) and 10(-6) M. At the same concentration, TPTC, itself, caused neither the release of histamine nor any change in cell viability which was supported by the activity of lactate dehydrogenase (LDH) from purified rat peritoneal mast cells. All this evidence suggests that TPTC has an inhibitory effect on the release of histamine from mast cells without direct cytotoxicity.", "contents": "Effect of triphenyltin chloride on the release of histamine from mast cells. The effects of triphenyltin chloride (TPTC) on the release of histamine from rat and mouse mast cells in vitro and in vivo were investigated. The results obtained are summarized as follows: (a) At doses between 1 and 3 mg/kg, TPTC inhibited the dye leakage due to passive cutaneous anaphylaxis mediated by IgE antibody in mouse ear. At the same doses, TPTC inhibited the swelling due to reversed cutaneous anaphylaxis mediated by IgG antibody in rat. However, TPTC did not affect dye leakage due to histamine, serotonin, and LTC4 in rat skin; (b) Histamine release by antigen and IgE antibody in rat peritoneal cavity was inhibited by the administration of TPTC at doses between 0.3 and 3 mg/kg; (c) Histamine release by calcium ionophore A 23187 from purified rat peritoneal mast cells in vitro was inhibited by TPTC at concentrations between 10(-7) and 10(-6) M. At the same concentration, TPTC, itself, caused neither the release of histamine nor any change in cell viability which was supported by the activity of lactate dehydrogenase (LDH) from purified rat peritoneal mast cells. All this evidence suggests that TPTC has an inhibitory effect on the release of histamine from mast cells without direct cytotoxicity."} {"id": "PMID:1280084", "title": "Effect of SA-103 on experimental allergic models in vivo and in vitro--comparison with disodium cromoglycate.", "content": "The anti-allergic action of N-[4-(4-methoxyphenyl)-2-thiazolyl]-1H-tetrazol-5-carboxamide (SA-103) was investigated and compared with that of disodium cromoglycate (DSCG). 1) Oral administration of SA-103 (0.1-10 mg/kg, p.o.) showed dose-dependent inhibition of 48 hr homologous passive cutaneous anaphylaxis (PCA) in rats. The inhibition rate (50%) of the compound at 1 mg/kg was comparable to that of DSCG at 1 mg/kg (i.v.). 2) Both of the drugs concentration-dependently inhibited the release of in vitro anaphylactic histamine from rat peritoneal exudate cells, but SA-103 was 1,000 times as potent as DSCG. 3) High doses (50 and 100 mg/kg, p.o.) of SA-103 tended to suppress 7-day homologous PCA in guinea pigs by only 20-30%. DSCG (100 mg/kg, i.v.) did not influence the reaction. 4) Neither anaphylactic histamine nor leukotriene release from guinea pig lung fragments was markedly influenced by SA-103 (10(-8)-10(-5) g/ml) or DSCG (10(-5)-10(-3) g/ml). 5) The histamine and serotonin induced contractions of the isolated guinea pig ileum were minimally enhanced or suppressed by very high concentrations (10(-4) g/ml) of SA-103 and DSCG. In addition to the above results, prolonged treatment with either compound before antigen challenge decreased the inhibitory response to anaphylactic histamine release from rat peritoneal cells. It is suggested, therefore, that the main mechanism(s) of the anti-allergic action of SA-103 is similar to that of DSCG, and SA-103 may be expected to be effective against allergic diseases.", "contents": "Effect of SA-103 on experimental allergic models in vivo and in vitro--comparison with disodium cromoglycate. The anti-allergic action of N-[4-(4-methoxyphenyl)-2-thiazolyl]-1H-tetrazol-5-carboxamide (SA-103) was investigated and compared with that of disodium cromoglycate (DSCG). 1) Oral administration of SA-103 (0.1-10 mg/kg, p.o.) showed dose-dependent inhibition of 48 hr homologous passive cutaneous anaphylaxis (PCA) in rats. The inhibition rate (50%) of the compound at 1 mg/kg was comparable to that of DSCG at 1 mg/kg (i.v.). 2) Both of the drugs concentration-dependently inhibited the release of in vitro anaphylactic histamine from rat peritoneal exudate cells, but SA-103 was 1,000 times as potent as DSCG. 3) High doses (50 and 100 mg/kg, p.o.) of SA-103 tended to suppress 7-day homologous PCA in guinea pigs by only 20-30%. DSCG (100 mg/kg, i.v.) did not influence the reaction. 4) Neither anaphylactic histamine nor leukotriene release from guinea pig lung fragments was markedly influenced by SA-103 (10(-8)-10(-5) g/ml) or DSCG (10(-5)-10(-3) g/ml). 5) The histamine and serotonin induced contractions of the isolated guinea pig ileum were minimally enhanced or suppressed by very high concentrations (10(-4) g/ml) of SA-103 and DSCG. In addition to the above results, prolonged treatment with either compound before antigen challenge decreased the inhibitory response to anaphylactic histamine release from rat peritoneal cells. It is suggested, therefore, that the main mechanism(s) of the anti-allergic action of SA-103 is similar to that of DSCG, and SA-103 may be expected to be effective against allergic diseases."} {"id": "PMID:1280085", "title": "[The reactivity of dispersed human lung mast cells and peripheral blood basophils to acetylcholine].", "content": "To clarify the relation between human lung mast cells and parasympathetic nerve function as well as IgE mediated allergic reactions, highly purified dispersed human lung mast cells were obtained by using the techniques of scissors dispersion, enzymatic treatment, percoll centrifugation and exclusion of adherent cells. The reactivity to acetylcholine was examined by observing the histamine release of purified mast cells. Moreover, peripheral blood basophils, which have many functional similarities with mast cells, were also examined in the same manner. The following results were obtained; 1) Histamine was significantly released from dispersed human lung mast cells at a final concentration of 10(-5) M acetylcholine (p less than 0.05); the peak of histamine release was 10(-4) M of acetylcholine. Acetylcholine had the additional effect of releasing histamine in response to anti-IgE. Histamine release was partially inhibited by 10(-5) M atropine. 2) Basophils had no response to acetylcholine. These results suggest that human lung mast cells play an important role in the defensive mechanism as an effector cell of acetylcholine-mediated autonomic nerve system as well as IgE-mediated allergic reaction.", "contents": "[The reactivity of dispersed human lung mast cells and peripheral blood basophils to acetylcholine]. To clarify the relation between human lung mast cells and parasympathetic nerve function as well as IgE mediated allergic reactions, highly purified dispersed human lung mast cells were obtained by using the techniques of scissors dispersion, enzymatic treatment, percoll centrifugation and exclusion of adherent cells. The reactivity to acetylcholine was examined by observing the histamine release of purified mast cells. Moreover, peripheral blood basophils, which have many functional similarities with mast cells, were also examined in the same manner. The following results were obtained; 1) Histamine was significantly released from dispersed human lung mast cells at a final concentration of 10(-5) M acetylcholine (p less than 0.05); the peak of histamine release was 10(-4) M of acetylcholine. Acetylcholine had the additional effect of releasing histamine in response to anti-IgE. Histamine release was partially inhibited by 10(-5) M atropine. 2) Basophils had no response to acetylcholine. These results suggest that human lung mast cells play an important role in the defensive mechanism as an effector cell of acetylcholine-mediated autonomic nerve system as well as IgE-mediated allergic reaction."} {"id": "PMID:1280086", "title": "[Inhibitory effects of cyclosporin A and FK-506 on eosinophil chemotactic factor activity in culture supernatants of mononuclear cells from asthmatics].", "content": "We have previously reported that the 5-day culture supernatants of peripheral blood mononuclear cells (PBMC) from Dermatophagides farinae (DF) sensitive asthmatics stimulated with 10 ng/ml DF antigen contain eosinophil chemotactic activity (ECA) with an apparent molecular weight greater than 30000 Da. In the present study, we examined the effects of CyA and FK on the ECA. ECA was tested using modified Boyden chamber method. We found that when CyA or FK was added to the culture throughout the experiment, the production of the factors with ECA by PBMC was inhibited in a dose-dependent manner. These inhibitory effects were unchanged by the addition of a sufficient dose of IL-2 to the culture medium. Isoelectrofocusing of the PBMC culture supernatants consistently yielded a major ECF activity at pH 7.0-7.5. The addition of CyA inhibited this major peak. In conclusion, these results suggest that mononuclear cells stimulated with related antigen produce substances which possess ECA and that CyA and FK can block the production of this substance. Therefore, there is a possibility that an immunosuppressive agent may be useful in bronchial asthma therapy by inhibiting the migration of eosinophils.", "contents": "[Inhibitory effects of cyclosporin A and FK-506 on eosinophil chemotactic factor activity in culture supernatants of mononuclear cells from asthmatics]. We have previously reported that the 5-day culture supernatants of peripheral blood mononuclear cells (PBMC) from Dermatophagides farinae (DF) sensitive asthmatics stimulated with 10 ng/ml DF antigen contain eosinophil chemotactic activity (ECA) with an apparent molecular weight greater than 30000 Da. In the present study, we examined the effects of CyA and FK on the ECA. ECA was tested using modified Boyden chamber method. We found that when CyA or FK was added to the culture throughout the experiment, the production of the factors with ECA by PBMC was inhibited in a dose-dependent manner. These inhibitory effects were unchanged by the addition of a sufficient dose of IL-2 to the culture medium. Isoelectrofocusing of the PBMC culture supernatants consistently yielded a major ECF activity at pH 7.0-7.5. The addition of CyA inhibited this major peak. In conclusion, these results suggest that mononuclear cells stimulated with related antigen produce substances which possess ECA and that CyA and FK can block the production of this substance. Therefore, there is a possibility that an immunosuppressive agent may be useful in bronchial asthma therapy by inhibiting the migration of eosinophils."} {"id": "PMID:1280087", "title": "[Effect of a leukotriene B4 antagonist on substance P-induced granulocyte infiltration in mouse skin].", "content": "Substance P causes granulocyte (neutrophil and eosinophil) infiltration in mouse skin by inducing mast cell degranulation. However, the mediator responsible for this granulocyte infiltration has not been determined. In this study, we examined the effect of a leukotriene B4 (LTB4) antagonist ONO-4057 on substance P-induced granulocyte infiltration in the skin of BALB/c mice. Pretreatment with the LTB4 antagonist decreased substance P-induced neutrophil and eosinophil infiltrations in mouse skin at 6 h to the same extent that an inhibitor of mast cell degranulation disodium cromoglycate decreased those responses. The LTB4 antagonist also decreased substance P-induced neutrophil, but not eosinophil, infiltration in mouse skin at 24 h. We conclude that LTB4 is a major mast cell-derived chemotactic mediator for initiating substance P-induced neutrophil and eosinophil infiltrations in mouse skin.", "contents": "[Effect of a leukotriene B4 antagonist on substance P-induced granulocyte infiltration in mouse skin]. Substance P causes granulocyte (neutrophil and eosinophil) infiltration in mouse skin by inducing mast cell degranulation. However, the mediator responsible for this granulocyte infiltration has not been determined. In this study, we examined the effect of a leukotriene B4 (LTB4) antagonist ONO-4057 on substance P-induced granulocyte infiltration in the skin of BALB/c mice. Pretreatment with the LTB4 antagonist decreased substance P-induced neutrophil and eosinophil infiltrations in mouse skin at 6 h to the same extent that an inhibitor of mast cell degranulation disodium cromoglycate decreased those responses. The LTB4 antagonist also decreased substance P-induced neutrophil, but not eosinophil, infiltration in mouse skin at 24 h. We conclude that LTB4 is a major mast cell-derived chemotactic mediator for initiating substance P-induced neutrophil and eosinophil infiltrations in mouse skin."} {"id": "PMID:1280088", "title": "[The culture of mouse bone marrow-derived mast cells (BMMC) and the anaphylactic release of chemical mediators].", "content": "Bone marrow cells from BALB/c, C3H/He and WBB6F1+/+ mice were cultured for 5 wks in the presence of the culture supernatant from prokoweed mitogen-stimulated spleen cells to assess and compare the degree of growth, proliferation and chemical mediator release of the mast cells (BMMC) derived from them. BMMC, which were positive to alcian blue staining, were found in the suspension cells on the culture of the bone marrow cells of either species of mice after 2 wk culture. The percentages of BMMC in the suspension cells were increased with time of culture, reaching more than 90% after 5 wks. No differences in the growth and proliferation rate among BMMC from these three species were observed. However, in regard to the amount of anaphylactic leukotriene (LT) and histamine release. BMMC from BALB/c mice were superior to those from other species. From the above results, subsequent experiments were executed with BMMC from BALB/c mice. There was no obvious difference in the releasability of anaphylactic mediators among BMMC obtained at any stages of the passage during 4-12 wk culture. On the other hand, although BMMC cultured for 4 and 5 wks well responded to Ca ionophore A23187 for these mediator release, those for 6 to 12 wks obviously deteriorated with prolongation of the culture. The time course of the anaphylactic release of immunoreactive (i-) LTB4, i-LTC4 and histamine from BMMC revealed that almost maximum release was reached at 10, 20 and 5 min, respectively, after antigen challenge. Several drugs including antiallergics and beta-stimulants had no effect on their release. From these results, it is suggested that present BMMC may be inadequate cells for evaluation of antiallergic drugs that can inhibit the anaphylactic mediator release, but may be useful for the research of the mechanism of the release because the cells likely release the mediators without occurrence of complicated subordinate reactions.", "contents": "[The culture of mouse bone marrow-derived mast cells (BMMC) and the anaphylactic release of chemical mediators]. Bone marrow cells from BALB/c, C3H/He and WBB6F1+/+ mice were cultured for 5 wks in the presence of the culture supernatant from prokoweed mitogen-stimulated spleen cells to assess and compare the degree of growth, proliferation and chemical mediator release of the mast cells (BMMC) derived from them. BMMC, which were positive to alcian blue staining, were found in the suspension cells on the culture of the bone marrow cells of either species of mice after 2 wk culture. The percentages of BMMC in the suspension cells were increased with time of culture, reaching more than 90% after 5 wks. No differences in the growth and proliferation rate among BMMC from these three species were observed. However, in regard to the amount of anaphylactic leukotriene (LT) and histamine release. BMMC from BALB/c mice were superior to those from other species. From the above results, subsequent experiments were executed with BMMC from BALB/c mice. There was no obvious difference in the releasability of anaphylactic mediators among BMMC obtained at any stages of the passage during 4-12 wk culture. On the other hand, although BMMC cultured for 4 and 5 wks well responded to Ca ionophore A23187 for these mediator release, those for 6 to 12 wks obviously deteriorated with prolongation of the culture. The time course of the anaphylactic release of immunoreactive (i-) LTB4, i-LTC4 and histamine from BMMC revealed that almost maximum release was reached at 10, 20 and 5 min, respectively, after antigen challenge. Several drugs including antiallergics and beta-stimulants had no effect on their release. From these results, it is suggested that present BMMC may be inadequate cells for evaluation of antiallergic drugs that can inhibit the anaphylactic mediator release, but may be useful for the research of the mechanism of the release because the cells likely release the mediators without occurrence of complicated subordinate reactions."} {"id": "PMID:1280089", "title": "[Effect of tazanolast on platelet activating factor-induced airway hyperresponsiveness in guinea pigs].", "content": "To determine whether tazanolast inhibits airway hyperresponsiveness, we studied the effect of this drug on platelet activating factor (PAF)-induced airway hyperresponsiveness in guinea pigs. Inhalation of PAF (1 microgram/ml) caused significant airway hyperresponsiveness to acetylcholine (p < 0.01) or histamine (p < 0.05). Pretreatment with tazanolast (30-300 mg/kg) produced a dose-dependent inhibition of airway hyperresponsiveness induced by PAF inhalation, and significant inhibition (p < 0.05) was obtained with the drug (300 mg/kg). Aspirin also inhibited PAF-induced airway hyperresponsiveness, while tranilast produced hardly any inhibition. From these results, it is suggested that tazanolast is effective in inhibiting airway hyperresponsiveness.", "contents": "[Effect of tazanolast on platelet activating factor-induced airway hyperresponsiveness in guinea pigs]. To determine whether tazanolast inhibits airway hyperresponsiveness, we studied the effect of this drug on platelet activating factor (PAF)-induced airway hyperresponsiveness in guinea pigs. Inhalation of PAF (1 microgram/ml) caused significant airway hyperresponsiveness to acetylcholine (p < 0.01) or histamine (p < 0.05). Pretreatment with tazanolast (30-300 mg/kg) produced a dose-dependent inhibition of airway hyperresponsiveness induced by PAF inhalation, and significant inhibition (p < 0.05) was obtained with the drug (300 mg/kg). Aspirin also inhibited PAF-induced airway hyperresponsiveness, while tranilast produced hardly any inhibition. From these results, it is suggested that tazanolast is effective in inhibiting airway hyperresponsiveness."} {"id": "PMID:1280090", "title": "The effect of NH4Cl on Rb+ fluxes in resting and stimulated rat submandibular acinar cells.", "content": "Dispersed salivary acini isolated from the rat submandibular gland were incubated in a HEPES-buffered Krebs-Ringer solution or in the same buffer containing 20 mM NH4Cl and the accumulation and efflux of K+ were measured with the radiotracer 86Rb+, in the presence and absence of acetylcholine and of transport inhibitors. Exposure to NH4Cl caused a significant (greater than 50%) reduction in tracer accumulation. This effect was blocked by 0.1 mM bumetanide, but not by 1 mM ouabain. The effect of NH4Cl was, on the other hand, nearly additive with that of 1 microM acetylcholine. In cells preincubated with tracer, acute addition of NH4Cl caused a significant net efflux of isotope, so that the tracer content fell to 45% of the control value within 10 min. Bumetanide added to preloaded cells in the same fashion had no effect on tracer content and did not modify the efflux of 86Rb+ induced by 1 microM acetylcholine. However, this inhibitor essentially abolished the NH4Cl-induced tracer efflux. Exposure to NH4Cl during tracer loading did not appear to affect subsequent agonist-stimulated tracer efflux. These results suggest that: (1) the inhibition of K+ entry by NH4Cl is due to an effective competition by the NH4+ ion with Rb+ (and K+) for uptake via a bumetanide-sensitive Na+/K+/2Cl- contransporter.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "The effect of NH4Cl on Rb+ fluxes in resting and stimulated rat submandibular acinar cells. Dispersed salivary acini isolated from the rat submandibular gland were incubated in a HEPES-buffered Krebs-Ringer solution or in the same buffer containing 20 mM NH4Cl and the accumulation and efflux of K+ were measured with the radiotracer 86Rb+, in the presence and absence of acetylcholine and of transport inhibitors. Exposure to NH4Cl caused a significant (greater than 50%) reduction in tracer accumulation. This effect was blocked by 0.1 mM bumetanide, but not by 1 mM ouabain. The effect of NH4Cl was, on the other hand, nearly additive with that of 1 microM acetylcholine. In cells preincubated with tracer, acute addition of NH4Cl caused a significant net efflux of isotope, so that the tracer content fell to 45% of the control value within 10 min. Bumetanide added to preloaded cells in the same fashion had no effect on tracer content and did not modify the efflux of 86Rb+ induced by 1 microM acetylcholine. However, this inhibitor essentially abolished the NH4Cl-induced tracer efflux. Exposure to NH4Cl during tracer loading did not appear to affect subsequent agonist-stimulated tracer efflux. These results suggest that: (1) the inhibition of K+ entry by NH4Cl is due to an effective competition by the NH4+ ion with Rb+ (and K+) for uptake via a bumetanide-sensitive Na+/K+/2Cl- contransporter.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280091", "title": "Effects of the beta-adrenoceptor antagonists atenolol and propranolol on human whole saliva flow rate and composition.", "content": "The effects of beta-adrenoceptor antagonists on salivary secretion have been extensively studied in animals but not in man. The aim here was to compare salivary flow rate and composition in man during 1 week of treatment with a non-selective (propranolol 80 mg b.i.d.) and a beta 1-selective (atenolol 50 mg o.d.) antagonist with that of placebo. The randomized, double-blind, cross-over (\"Latin square\") design was used and 42 healthy male volunteers were recruited to the study. The treatment periods were separated by a wash-out period of 2 weeks. Whole saliva was sampled on day 0 (before) and on day 7 during each treatment. The plasma concentration of propranolol and atenolol was determined from blood samples obtained on day 7. Resting saliva was assessed for flow rate, amylase activity and concentration of total protein, hexosamine and sialic acid. Stimulated saliva was assessed for flow rate, pH, buffer pH, amylase activity and concentration of total protein, Ca2+, Mg2+, Na+, K+, Cl- and PO4(2-). In resting as well as stimulated whole saliva both the total protein concentration and the amylase activity were significantly decreased during the active treatment periods (p less than 0.05-p less than 0.001). At lunchtime during atenolol treatment the hexosamine/total protein and the sialic acid/total protein ratios were significantly increased (p less than 0.05-p less than 0.01), suggesting a possible effect on protein synthesis. In addition, the concentrations of Ca2+, PO4(2-), Cl- and Mg2+ were significantly altered during the active treatment periods (p less than 0.05-p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of the beta-adrenoceptor antagonists atenolol and propranolol on human whole saliva flow rate and composition. The effects of beta-adrenoceptor antagonists on salivary secretion have been extensively studied in animals but not in man. The aim here was to compare salivary flow rate and composition in man during 1 week of treatment with a non-selective (propranolol 80 mg b.i.d.) and a beta 1-selective (atenolol 50 mg o.d.) antagonist with that of placebo. The randomized, double-blind, cross-over (\"Latin square\") design was used and 42 healthy male volunteers were recruited to the study. The treatment periods were separated by a wash-out period of 2 weeks. Whole saliva was sampled on day 0 (before) and on day 7 during each treatment. The plasma concentration of propranolol and atenolol was determined from blood samples obtained on day 7. Resting saliva was assessed for flow rate, amylase activity and concentration of total protein, hexosamine and sialic acid. Stimulated saliva was assessed for flow rate, pH, buffer pH, amylase activity and concentration of total protein, Ca2+, Mg2+, Na+, K+, Cl- and PO4(2-). In resting as well as stimulated whole saliva both the total protein concentration and the amylase activity were significantly decreased during the active treatment periods (p less than 0.05-p less than 0.001). At lunchtime during atenolol treatment the hexosamine/total protein and the sialic acid/total protein ratios were significantly increased (p less than 0.05-p less than 0.01), suggesting a possible effect on protein synthesis. In addition, the concentrations of Ca2+, PO4(2-), Cl- and Mg2+ were significantly altered during the active treatment periods (p less than 0.05-p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280093", "title": "Multiple sclerosis: common management issues.", "content": "Multiple sclerosis, the commonest neurological disease of young Australians, has a wide range of symptoms and may lead to varying degrees of physical and cognitive disability. Characteristically, the disease runs an episodic course, but it may be progressive from the outset. To date, treatments aimed at modifying the disease process have been disappointing, but recognition and management of the symptoms have improved, leading to an improved quality of life for people with multiple sclerosis.", "contents": "Multiple sclerosis: common management issues. Multiple sclerosis, the commonest neurological disease of young Australians, has a wide range of symptoms and may lead to varying degrees of physical and cognitive disability. Characteristically, the disease runs an episodic course, but it may be progressive from the outset. To date, treatments aimed at modifying the disease process have been disappointing, but recognition and management of the symptoms have improved, leading to an improved quality of life for people with multiple sclerosis."} {"id": "PMID:1280094", "title": "Symptomatic choroidal metastases in breast cancer.", "content": "A series of 21 consecutive patients with carcinoma of the breast and symptomatic choroidal metastases was reviewed. All patients were symptomatic of choroidal metastases at presentation. Most patients had disease progression at other sites at the time of diagnosis. The incidence of cerebral metastases was not increased in this group compared to that in patients with metastatic breast cancer at other sites. Radiotherapy using a direct anterior field proved effective palliation for this disease site. Of the 32 eyes treated, serial visual acuity was documented in 23. Seventeen showed objective improvement and six showed stabilisation. The median duration of improvement was 11.5 months.", "contents": "Symptomatic choroidal metastases in breast cancer. A series of 21 consecutive patients with carcinoma of the breast and symptomatic choroidal metastases was reviewed. All patients were symptomatic of choroidal metastases at presentation. Most patients had disease progression at other sites at the time of diagnosis. The incidence of cerebral metastases was not increased in this group compared to that in patients with metastatic breast cancer at other sites. Radiotherapy using a direct anterior field proved effective palliation for this disease site. Of the 32 eyes treated, serial visual acuity was documented in 23. Seventeen showed objective improvement and six showed stabilisation. The median duration of improvement was 11.5 months."} {"id": "PMID:1280095", "title": "Prevalence of antibodies to hepatitis C virus in patients receiving renal replacement therapy, and in the staff caring for them.", "content": "Two hundred and forty-three patients receiving renal replacement therapy (RRT) and 20 renal unit staff were tested for antibodies to hepatitis C (HCV). Three patients (1.2%) were positive by the first generation test kit, the lowest rate in patients receiving RRT reported in the literature to date. These three, and eight other patients tested positive by the second generation kit, a prevalence rate of 4.5%. Anti-HCV antibody positivity was associated with higher mean serum alanine aminotransferase (p = 0.0003) and aspartate aminotransferase (p = 0.018) levels. However, only one of the 11 anti-HCV positive patients had liver transaminase levels more than twice the upper limit of the laboratory reference range. Anti-HCV positivity was associated with a higher mean number of units of blood transfused (p = 0.035). None of 20 staff were anti-HCV positive. Twenty-five of 212 (11.7%) patients reported a history of liver disease; none of these were anti-HCV positive. Hepatitis B surface antigen was detected in eight of 215 (3.7%) patients, of which three were e antigen positive. There was evidence of past hepatitis B infection in 53 of 215 (24.7%) patients, more frequently in Maoris (p = 0.001). Overall, significantly raised liver transaminases were present in three of 198 (1.5%) patients and in no staff. This unit has a remarkably low prevalence of antibodies to HCV, an observation supported by the low rate of abnormal serum liver enzymes.", "contents": "Prevalence of antibodies to hepatitis C virus in patients receiving renal replacement therapy, and in the staff caring for them. Two hundred and forty-three patients receiving renal replacement therapy (RRT) and 20 renal unit staff were tested for antibodies to hepatitis C (HCV). Three patients (1.2%) were positive by the first generation test kit, the lowest rate in patients receiving RRT reported in the literature to date. These three, and eight other patients tested positive by the second generation kit, a prevalence rate of 4.5%. Anti-HCV antibody positivity was associated with higher mean serum alanine aminotransferase (p = 0.0003) and aspartate aminotransferase (p = 0.018) levels. However, only one of the 11 anti-HCV positive patients had liver transaminase levels more than twice the upper limit of the laboratory reference range. Anti-HCV positivity was associated with a higher mean number of units of blood transfused (p = 0.035). None of 20 staff were anti-HCV positive. Twenty-five of 212 (11.7%) patients reported a history of liver disease; none of these were anti-HCV positive. Hepatitis B surface antigen was detected in eight of 215 (3.7%) patients, of which three were e antigen positive. There was evidence of past hepatitis B infection in 53 of 215 (24.7%) patients, more frequently in Maoris (p = 0.001). Overall, significantly raised liver transaminases were present in three of 198 (1.5%) patients and in no staff. This unit has a remarkably low prevalence of antibodies to HCV, an observation supported by the low rate of abnormal serum liver enzymes."} {"id": "PMID:1280096", "title": "The effect of age on the inflammatory response to arthritis-associated crystals.", "content": "The effect of age on the inflammatory response to urate and hydroxyapatite crystals was examined using both in vivo (intradermal skin testing) and in vitro (neutrophil death following incubation with urate crystals) methods. No significant difference in crystal-induced inflammation was found between young (< 25 years) and elderly (> 75 years) subjects and there was no correlation between the in vivo and in vitro tests. There was good correlation (0.63, p < 0.001) between the intradermal responses to urate and hydroxyapatite, suggesting that subjects, regardless of their age, are consistent in their response to these two types of arthritis-associated crystal. Advanced age does not lead to a major alteration in the inflammatory response to arthritis-associated crystals.", "contents": "The effect of age on the inflammatory response to arthritis-associated crystals. The effect of age on the inflammatory response to urate and hydroxyapatite crystals was examined using both in vivo (intradermal skin testing) and in vitro (neutrophil death following incubation with urate crystals) methods. No significant difference in crystal-induced inflammation was found between young (< 25 years) and elderly (> 75 years) subjects and there was no correlation between the in vivo and in vitro tests. There was good correlation (0.63, p < 0.001) between the intradermal responses to urate and hydroxyapatite, suggesting that subjects, regardless of their age, are consistent in their response to these two types of arthritis-associated crystal. Advanced age does not lead to a major alteration in the inflammatory response to arthritis-associated crystals."} {"id": "PMID:1280097", "title": "Overview of low molecular weight heparins and heparinoids: basic and clinical aspects.", "content": "Low molecular weight heparins (LMWHs) are fragments derived by enzymatic or chemical depolymerization of standard heparin (SH). They are approximately one-third the size of SH, with a mean molecular weight of 4,000 to 6,000. LMWHs produce less bleeding for equivalent antithrombotic effects than SH in experimental animals. Clinically LMWHs exhibit different pharmacokinetics than SH; they have much better bioavailability at low doses, a longer half life than SH and clearance pattern which is dose independent. In addition, LMWHs have a more predictable dose response than SH. These differences in pharmacokinetic properties occur because in contrast to SH, LMWHs show minimal binding to endothelium and plasma proteins. Clinical trials have demonstrated that LMWHs are effective and safe for the prevention and treatment of venous thromboembolism. In patients having orthopaedic surgery, LMWHs are more effective than low dose SH, more effective than dextran or warfarin. They are also more effective than SH in preventing venous thrombosis in stroke patients and those suffering spinal injury. In addition, recent studies suggest that LMWHs administered by subcutaneous injection in fixed weight-adjusted doses are at least as effective and safe as adjusted dose SH given by continuous intravenous infusion for the treatment of venous thrombosis.", "contents": "Overview of low molecular weight heparins and heparinoids: basic and clinical aspects. Low molecular weight heparins (LMWHs) are fragments derived by enzymatic or chemical depolymerization of standard heparin (SH). They are approximately one-third the size of SH, with a mean molecular weight of 4,000 to 6,000. LMWHs produce less bleeding for equivalent antithrombotic effects than SH in experimental animals. Clinically LMWHs exhibit different pharmacokinetics than SH; they have much better bioavailability at low doses, a longer half life than SH and clearance pattern which is dose independent. In addition, LMWHs have a more predictable dose response than SH. These differences in pharmacokinetic properties occur because in contrast to SH, LMWHs show minimal binding to endothelium and plasma proteins. Clinical trials have demonstrated that LMWHs are effective and safe for the prevention and treatment of venous thromboembolism. In patients having orthopaedic surgery, LMWHs are more effective than low dose SH, more effective than dextran or warfarin. They are also more effective than SH in preventing venous thrombosis in stroke patients and those suffering spinal injury. In addition, recent studies suggest that LMWHs administered by subcutaneous injection in fixed weight-adjusted doses are at least as effective and safe as adjusted dose SH given by continuous intravenous infusion for the treatment of venous thrombosis."} {"id": "PMID:1280098", "title": "An intra-thyroidal branchial cyst: a case report.", "content": "Branchial cleft cysts were previously thought not to occur in the thyroid but have recently been described in two patients with Hashimoto's disease. This case report describes a patient with a branchial cleft cyst in an otherwise normal thyroid gland and could provide further evidence that thyroidal follicular cells are derived from the branchial clefts as well as from the primitive gut.", "contents": "An intra-thyroidal branchial cyst: a case report. Branchial cleft cysts were previously thought not to occur in the thyroid but have recently been described in two patients with Hashimoto's disease. This case report describes a patient with a branchial cleft cyst in an otherwise normal thyroid gland and could provide further evidence that thyroidal follicular cells are derived from the branchial clefts as well as from the primitive gut."} {"id": "PMID:1280099", "title": "Non small cell carcinoma of the lung. A retrospective study. Presented at the 41st annual meeting of the Royal Australasian College of Radiologists, September 1990, Perth.", "content": "A retrospective study was undertaken in 1990 of 188 patients with the diagnosis of non small cell carcinoma of the lung referred to the Department of Radiation Oncology in 1984. Most patients (178/188) received a course of radiotherapy. This was definitive in 23, palliative in 148 (primary site in 113, metastases in 16, primary plus metastases in 19) and postoperative in 7. This report is a 5 year followup of the 171 patients treated by radiation alone, to assess factors that influence survival. Tumour histology was 50% squamous, 23% adenocarcinoma, 16% large cell and 4% unspecified, non small cell carcinoma. In 8% no histological diagnosis was obtained. The most common symptoms were cough (44%), dyspnoea (43%), chest pain (37%), haemoptysis (33%) and systemic symptoms (36%). Tumour stage (TNM) was assessed retrospectively as I(5%), II(8%), IIIA(18%), IIIB(22%) and IV(28%). A subgroup of 31 cases (18%) of uncertain staging (I-III) was analysed separately and in 2 cases (1%) no staging information was available. Palliative intent of treatment and poorer performance status were related significantly to increasing stage of disease. The effects of palliative treatment were recorded in 79 cases; in 71 there was a reduction in symptoms. The median survival from diagnosis was 8 months (range < 1-72). Using univariate and multivariate analyses, significant and independent prognostic factors for improved survival were good performance status, absence of systemic symptoms, lower tumour stage and curative intent of treatment (higher radiation dose). However the 5-year survival was only 2%. Long-term survival was associated predominantly with early stage disease but not with the type or intent of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Non small cell carcinoma of the lung. A retrospective study. Presented at the 41st annual meeting of the Royal Australasian College of Radiologists, September 1990, Perth. A retrospective study was undertaken in 1990 of 188 patients with the diagnosis of non small cell carcinoma of the lung referred to the Department of Radiation Oncology in 1984. Most patients (178/188) received a course of radiotherapy. This was definitive in 23, palliative in 148 (primary site in 113, metastases in 16, primary plus metastases in 19) and postoperative in 7. This report is a 5 year followup of the 171 patients treated by radiation alone, to assess factors that influence survival. Tumour histology was 50% squamous, 23% adenocarcinoma, 16% large cell and 4% unspecified, non small cell carcinoma. In 8% no histological diagnosis was obtained. The most common symptoms were cough (44%), dyspnoea (43%), chest pain (37%), haemoptysis (33%) and systemic symptoms (36%). Tumour stage (TNM) was assessed retrospectively as I(5%), II(8%), IIIA(18%), IIIB(22%) and IV(28%). A subgroup of 31 cases (18%) of uncertain staging (I-III) was analysed separately and in 2 cases (1%) no staging information was available. Palliative intent of treatment and poorer performance status were related significantly to increasing stage of disease. The effects of palliative treatment were recorded in 79 cases; in 71 there was a reduction in symptoms. The median survival from diagnosis was 8 months (range < 1-72). Using univariate and multivariate analyses, significant and independent prognostic factors for improved survival were good performance status, absence of systemic symptoms, lower tumour stage and curative intent of treatment (higher radiation dose). However the 5-year survival was only 2%. Long-term survival was associated predominantly with early stage disease but not with the type or intent of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280100", "title": "Combined chemotherapy using cisplatin, ifosfamide and bleomycin (PIB) in the treatment of advanced and recurrent cervical carcinoma.", "content": "Combined cisplatin, ifosfamide and bleomycin (PIB) chemotherapy was given to 14 (11 recurrent and 3 advanced and metastatic) cervical carcinoma patients. At least 2 cycles of chemotherapy were given before assessment of tumour response. The overall response rate was 28.6%; the complete response rate was 14.3%. Sites of response included cervical lymph nodes and the lung. Toxicity was common. Alopecia was universal. Other toxicity included suppression of haematopoiesis (73%), leucopenia (71%) and nausea and vomiting. Two patients died from sepsis during the myelosuppressive phase. The role of PIB in the management of advanced and recurrent carcinoma of the cervix should be evaluated in a randomized-controlled trial.", "contents": "Combined chemotherapy using cisplatin, ifosfamide and bleomycin (PIB) in the treatment of advanced and recurrent cervical carcinoma. Combined cisplatin, ifosfamide and bleomycin (PIB) chemotherapy was given to 14 (11 recurrent and 3 advanced and metastatic) cervical carcinoma patients. At least 2 cycles of chemotherapy were given before assessment of tumour response. The overall response rate was 28.6%; the complete response rate was 14.3%. Sites of response included cervical lymph nodes and the lung. Toxicity was common. Alopecia was universal. Other toxicity included suppression of haematopoiesis (73%), leucopenia (71%) and nausea and vomiting. Two patients died from sepsis during the myelosuppressive phase. The role of PIB in the management of advanced and recurrent carcinoma of the cervix should be evaluated in a randomized-controlled trial."} {"id": "PMID:1280101", "title": "Protein kinase A modulates Ca(2+)- and protein kinase C-dependent amylase release in permeabilized rat pancreatic acini.", "content": "The role of protein kinase A (PKA) in the release of amylase from permeabilized pancreatic acini was investigated. Addition of cyclic AMP (cAMP) to permeabilized acini resulted in a potentiation of Ca(2+)-dependent amylase release, shifting the Ca2+ dose/response curve leftwards. As with protein kinase C (PKC) activation, this is due to an increase in the time of active discharge. The effect of cAMP was shown to be blocked by two inhibitors of PKA, H89 and the PKI-(5-24)-peptide. At low concentration, cAMP synergizes from phorbol 12-myristate 13-acetate (PMA), while at optimal concentrations cAMP and PMA are additive. PKA and PKC appear to work via similar, but not identical mechanisms.", "contents": "Protein kinase A modulates Ca(2+)- and protein kinase C-dependent amylase release in permeabilized rat pancreatic acini. The role of protein kinase A (PKA) in the release of amylase from permeabilized pancreatic acini was investigated. Addition of cyclic AMP (cAMP) to permeabilized acini resulted in a potentiation of Ca(2+)-dependent amylase release, shifting the Ca2+ dose/response curve leftwards. As with protein kinase C (PKC) activation, this is due to an increase in the time of active discharge. The effect of cAMP was shown to be blocked by two inhibitors of PKA, H89 and the PKI-(5-24)-peptide. At low concentration, cAMP synergizes from phorbol 12-myristate 13-acetate (PMA), while at optimal concentrations cAMP and PMA are additive. PKA and PKC appear to work via similar, but not identical mechanisms."} {"id": "PMID:1280102", "title": "Role of the scavenger receptor in the uptake of methylamine-activated alpha 2-macroglobulin by rat liver.", "content": "Alpha 2-Macroglobulin (alpha 2M) requires activation by small nucleophiles (e.g. methylamine; giving alpha 2M-Me) or proteolytic enzymes (e.g. trypsin; giving alpha 2M-Tr) in order to be rapidly removed from the circulation by the liver. Separation of rat liver cells into parenchymal, endothelial and Kupffer cells at 10 min after injection indicates that liver uptake of alpha 2M-Me is shared between parenchymal and endothelial cells, with relative contributions of 51.3% and 48.3% respectively of total liver-associated radioactivity. In contrast, alpha 2M-Tr is almost exclusively taken up by the parenchymal cells (90.1% of liver-associated radioactivity). A preinjection of 5 mg of poly(inosinic acid) decreased liver uptake of alpha 2M-Me to 39.9% of the control value, while it had no effect on liver uptake of alpha 2M-Tr. It appears that poly(inosinic acid) specifically reduces the uptake of alpha 2M-Me in vivo by endothelial cells, leaving uptake by parenchymal cells unaffected. In vitro studies with isolated liver cells indicate that the association of alpha 2M-Me with endothelial cells is 21-fold higher per mg of cell protein than with parenchymal cells. The capacity of endothelial cells to degrade alpha 2M-Me appears to be 46 times higher than that of parenchymal cells. Competition studies show that poly(inosinic acid) or acetylated low-density lipoprotein effectively competes with the association of alpha 2M-Me with endothelial and Kupffer cells, but association with parenchymal cells is unaffected. It is suggested that activation of alpha 2M by methylamine induces a charge distribution on the protein which triggers specific uptake by the scavenger receptor on endothelial cells. It is concluded that the uptake of alpha 2M-Me by the scavenger receptor might function as an additional system for the uptake of activated alpha 2M.", "contents": "Role of the scavenger receptor in the uptake of methylamine-activated alpha 2-macroglobulin by rat liver. Alpha 2-Macroglobulin (alpha 2M) requires activation by small nucleophiles (e.g. methylamine; giving alpha 2M-Me) or proteolytic enzymes (e.g. trypsin; giving alpha 2M-Tr) in order to be rapidly removed from the circulation by the liver. Separation of rat liver cells into parenchymal, endothelial and Kupffer cells at 10 min after injection indicates that liver uptake of alpha 2M-Me is shared between parenchymal and endothelial cells, with relative contributions of 51.3% and 48.3% respectively of total liver-associated radioactivity. In contrast, alpha 2M-Tr is almost exclusively taken up by the parenchymal cells (90.1% of liver-associated radioactivity). A preinjection of 5 mg of poly(inosinic acid) decreased liver uptake of alpha 2M-Me to 39.9% of the control value, while it had no effect on liver uptake of alpha 2M-Tr. It appears that poly(inosinic acid) specifically reduces the uptake of alpha 2M-Me in vivo by endothelial cells, leaving uptake by parenchymal cells unaffected. In vitro studies with isolated liver cells indicate that the association of alpha 2M-Me with endothelial cells is 21-fold higher per mg of cell protein than with parenchymal cells. The capacity of endothelial cells to degrade alpha 2M-Me appears to be 46 times higher than that of parenchymal cells. Competition studies show that poly(inosinic acid) or acetylated low-density lipoprotein effectively competes with the association of alpha 2M-Me with endothelial and Kupffer cells, but association with parenchymal cells is unaffected. It is suggested that activation of alpha 2M by methylamine induces a charge distribution on the protein which triggers specific uptake by the scavenger receptor on endothelial cells. It is concluded that the uptake of alpha 2M-Me by the scavenger receptor might function as an additional system for the uptake of activated alpha 2M."} {"id": "PMID:1280103", "title": "Endothelin rapidly stimulates mitogen-activated protein kinase activity in rat mesangial cells.", "content": "Mitogen-activated protein (MAP) kinases are regarded as switch kinases in the phosphorylation cascade initiated by various agonists. We have investigated whether endothelins (ET), which are constrictor and mitogenic isopeptides, can increase MAP kinase activity in rat mesangial cells, using bovine myelin basic protein (MBP) as a substrate for an in vitro kinase assay. Treatment of quiescent mesangial cells with ET-1 rapidly stimulated a kinase activity which phosphorylated exogenous MBP. This stimulation was dose-dependent, with threshold responses at 1 nM-ET-1. Epidermal growth factor and thrombin also activated this kinase in mesangial cells. We also examined the ET signal transduction pathways leading to activation of MBP kinase. Pertussis toxin had no effect on ET-stimulated MBP kinase activity. Stimulation of protein kinase C by phorbol ester increased MBP kinase activity, and down-regulation of PKC partially inhibited ET-stimulated MBP kinase as well as phorbol ester-stimulated MBP kinase activity. Interestingly, genestein, an inhibitor of protein tyrosine kinases, partially inhibited MBP kinase stimulated by ET but not by phorbol esters. These results suggest that ET stimulates MBP kinase activity in rat mesangial cells via at least two pathways: one which is protein kinase C-dependent and a second one that involves a protein tyrosine kinase. Finally, by raising rabbit antibodies against the two forms of MAP kinase, p44mapk and p42mapk, we demonstrated that both isoforms are expressed in mesangial cells. Antibody alpha 1 Cp42 specifically immunoprecipitated p42mapk and allowed us to demonstrate that ET stimulates MBP kinase activity in the p42mapk immunocomplex. In conclusion, we have provided evidence that, in rat mesangial cells, MAP kinases are rapidly activated by ET-1, a regulatory process that involves at least protein kinase C activation and also a contribution of a tyrosine kinase not yet characterized.", "contents": "Endothelin rapidly stimulates mitogen-activated protein kinase activity in rat mesangial cells. Mitogen-activated protein (MAP) kinases are regarded as switch kinases in the phosphorylation cascade initiated by various agonists. We have investigated whether endothelins (ET), which are constrictor and mitogenic isopeptides, can increase MAP kinase activity in rat mesangial cells, using bovine myelin basic protein (MBP) as a substrate for an in vitro kinase assay. Treatment of quiescent mesangial cells with ET-1 rapidly stimulated a kinase activity which phosphorylated exogenous MBP. This stimulation was dose-dependent, with threshold responses at 1 nM-ET-1. Epidermal growth factor and thrombin also activated this kinase in mesangial cells. We also examined the ET signal transduction pathways leading to activation of MBP kinase. Pertussis toxin had no effect on ET-stimulated MBP kinase activity. Stimulation of protein kinase C by phorbol ester increased MBP kinase activity, and down-regulation of PKC partially inhibited ET-stimulated MBP kinase as well as phorbol ester-stimulated MBP kinase activity. Interestingly, genestein, an inhibitor of protein tyrosine kinases, partially inhibited MBP kinase stimulated by ET but not by phorbol esters. These results suggest that ET stimulates MBP kinase activity in rat mesangial cells via at least two pathways: one which is protein kinase C-dependent and a second one that involves a protein tyrosine kinase. Finally, by raising rabbit antibodies against the two forms of MAP kinase, p44mapk and p42mapk, we demonstrated that both isoforms are expressed in mesangial cells. Antibody alpha 1 Cp42 specifically immunoprecipitated p42mapk and allowed us to demonstrate that ET stimulates MBP kinase activity in the p42mapk immunocomplex. In conclusion, we have provided evidence that, in rat mesangial cells, MAP kinases are rapidly activated by ET-1, a regulatory process that involves at least protein kinase C activation and also a contribution of a tyrosine kinase not yet characterized."} {"id": "PMID:1280104", "title": "Evolutionary conservation of the dystrophin central rod domain.", "content": "Dystrophin cDNA fragments encoding the C-terminal repeats of the central rod region have been expressed as fusion proteins. The polyclonal antisera raised to the purified fusion proteins have been characterized and neither antiserum cross-reacted with dystrophin-related protein. Antisera detected dystrophin with molecular mass close to that of the human in all terrestrial vertebrates and amphibia studied. Experiments with antisera to the N-terminal region of the dystrophin rod confirmed that epitopes to the rod region were conserved during this evolutionary period and the length of this domain remained unaltered.", "contents": "Evolutionary conservation of the dystrophin central rod domain. Dystrophin cDNA fragments encoding the C-terminal repeats of the central rod region have been expressed as fusion proteins. The polyclonal antisera raised to the purified fusion proteins have been characterized and neither antiserum cross-reacted with dystrophin-related protein. Antisera detected dystrophin with molecular mass close to that of the human in all terrestrial vertebrates and amphibia studied. Experiments with antisera to the N-terminal region of the dystrophin rod confirmed that epitopes to the rod region were conserved during this evolutionary period and the length of this domain remained unaltered."} {"id": "PMID:1280105", "title": "Purification and characterization of recombinant Xenopus poly(A)(+)-binding protein expressed in a baculovirus system.", "content": "The poly(A)(+)-binding protein (PABP) is a highly conserved protein that binds to the poly(A)+ tail of mRNAs. PABP has been shown to regulate message stability and translational efficiency, yet the mechanisms remain unknown. To facilitate further dissection of the functions of this protein, we have expressed and purified Xenopus PABP using a baculovirus expression system. At 48 h after infection of insect Spodoptera frugiperda (Sf9) cells with recombinant virus, approx. 3% of cell protein was PABP. Purification of PABP was achieved by affinity chromatography on poly(A)(+)-Sepharose. The purified protein was indistinguishable from Xenopus PABP with respect to its immunoreactivity and electrophoretic mobility. Furthermore, the recombinant PABP was expressed and purified as a functional protein as indicated by its ability to bind to poly(A)(+)-Sepharose and its ability to enhance the translation of adenylated messages in vitro. By comparing protein extracts from various developmental stages of Xenopus embryos with known amounts of purified PABP, we determined the amount of PABP per embryo. This analysis suggested that there is less than one PABP molecule available per PABP-binding site at early stages of development, and only a slight excess of PABP at later stages.", "contents": "Purification and characterization of recombinant Xenopus poly(A)(+)-binding protein expressed in a baculovirus system. The poly(A)(+)-binding protein (PABP) is a highly conserved protein that binds to the poly(A)+ tail of mRNAs. PABP has been shown to regulate message stability and translational efficiency, yet the mechanisms remain unknown. To facilitate further dissection of the functions of this protein, we have expressed and purified Xenopus PABP using a baculovirus expression system. At 48 h after infection of insect Spodoptera frugiperda (Sf9) cells with recombinant virus, approx. 3% of cell protein was PABP. Purification of PABP was achieved by affinity chromatography on poly(A)(+)-Sepharose. The purified protein was indistinguishable from Xenopus PABP with respect to its immunoreactivity and electrophoretic mobility. Furthermore, the recombinant PABP was expressed and purified as a functional protein as indicated by its ability to bind to poly(A)(+)-Sepharose and its ability to enhance the translation of adenylated messages in vitro. By comparing protein extracts from various developmental stages of Xenopus embryos with known amounts of purified PABP, we determined the amount of PABP per embryo. This analysis suggested that there is less than one PABP molecule available per PABP-binding site at early stages of development, and only a slight excess of PABP at later stages."} {"id": "PMID:1280106", "title": "Characterization of ruthenium red-binding sites of the Ca(2+)-ATPase from sarcoplasmic reticulum and their interaction with Ca(2+)-binding sites.", "content": "Sarcoplasmic reticulum Ca(2+)-ATPase has previously been shown to bind and dissociate two Ca2+ ions in a sequential mode. This behaviour is confirmed here by inducing sequential Ca2+ dissociation with Ruthenium Red. Ruthenium Red binds to sarcoplasmic reticulum vesicles (6 nmol/mg) with a Kd = 2 microM, producing biphasic kinetics of Ca2+ dissociation from the Ca(2+)-ATPase, decreasing the affinity for Ca2+ binding. Studies on the effect of Ca2+ on Ruthenium Red binding indicate that Ruthenium Red does not bind to the high-affinity Ca(2+)-binding sites, as suggested by the following observations: (i) micromolar concentrations of Ca2+ do not significantly alter Ruthenium Red binding to the sarcoplasmic reticulum; (ii) quenching of the fluorescence of fluorescein 5'-isothiocyanate (FITC) bound to Ca(2+)-ATPase by Ruthenium Red (resembling Ruthenium Red binding) is not prevented by micromolar concentrations of Ca2+; (iii) quenching of FITC fluorescence by Ca2+ binding to the high-affinity sites is achieved even though Ruthenium Red is bound to the Ca(2+)-ATPase; and (iv) micromolar Ca2+ concentrations prevent inhibition of the ATP-hydrolytic capability by dicyclohexylcarbodi-imide modification, but Ruthenium Red does not. However, micromolar concentrations of lanthanides (La3+ and Tb3+) and millimolar concentrations of bivalent cations (Ca2+ and Mg2+) inhibit Ruthenium Red binding as well as quenching of FITC-labelled Ca(2+)-ATPase fluorescence by Ruthenium Red. Studies of Ruthenium Red binding to tryptic fragments of Ca(2+)-ATPase, as demonstrated by ligand blotting, indicate that Ruthenium Red does not bind to the A1 subfragment. Our observations suggest that Ruthenium Red might bind to a cation-binding site in Ca(2+)-ATPase inducing fast release of the last bound Ca2+ by interactions between the sites.", "contents": "Characterization of ruthenium red-binding sites of the Ca(2+)-ATPase from sarcoplasmic reticulum and their interaction with Ca(2+)-binding sites. Sarcoplasmic reticulum Ca(2+)-ATPase has previously been shown to bind and dissociate two Ca2+ ions in a sequential mode. This behaviour is confirmed here by inducing sequential Ca2+ dissociation with Ruthenium Red. Ruthenium Red binds to sarcoplasmic reticulum vesicles (6 nmol/mg) with a Kd = 2 microM, producing biphasic kinetics of Ca2+ dissociation from the Ca(2+)-ATPase, decreasing the affinity for Ca2+ binding. Studies on the effect of Ca2+ on Ruthenium Red binding indicate that Ruthenium Red does not bind to the high-affinity Ca(2+)-binding sites, as suggested by the following observations: (i) micromolar concentrations of Ca2+ do not significantly alter Ruthenium Red binding to the sarcoplasmic reticulum; (ii) quenching of the fluorescence of fluorescein 5'-isothiocyanate (FITC) bound to Ca(2+)-ATPase by Ruthenium Red (resembling Ruthenium Red binding) is not prevented by micromolar concentrations of Ca2+; (iii) quenching of FITC fluorescence by Ca2+ binding to the high-affinity sites is achieved even though Ruthenium Red is bound to the Ca(2+)-ATPase; and (iv) micromolar Ca2+ concentrations prevent inhibition of the ATP-hydrolytic capability by dicyclohexylcarbodi-imide modification, but Ruthenium Red does not. However, micromolar concentrations of lanthanides (La3+ and Tb3+) and millimolar concentrations of bivalent cations (Ca2+ and Mg2+) inhibit Ruthenium Red binding as well as quenching of FITC-labelled Ca(2+)-ATPase fluorescence by Ruthenium Red. Studies of Ruthenium Red binding to tryptic fragments of Ca(2+)-ATPase, as demonstrated by ligand blotting, indicate that Ruthenium Red does not bind to the A1 subfragment. Our observations suggest that Ruthenium Red might bind to a cation-binding site in Ca(2+)-ATPase inducing fast release of the last bound Ca2+ by interactions between the sites."} {"id": "PMID:1280107", "title": "Studies on NG-methylarginine derivatives in myelin basic protein from developing and mutant mouse brain.", "content": "The amounts of NG-methylarginine derivatives in myelin basic protein (MBP) purified from dysmyelinating mutant and different stages of normal myelinating mouse brains have been studied by using h.p.l.c. with a highly sensitive post-column o-phthaldialdehyde derivative-formation method. All three naturally occurring derivatives (NG-monomethylarginine (MeArg), NGN'G-dimethylarginine [Me2(sym)Arg] and NGNG-dimethylarginine [Me2(asym)Arg]) were found in MBP; however, their relative concentrations varied significantly with the age of the animal. The amounts of MeArg and Me2(sym)Arg in MBP increased as a function of the age of the brain, whereas that of Me2(asym)Arg decreased. MBP from early-myelinating mouse brain was shown to contain a high proportion of Me2(asym)Arg, which was hardly detectable in older brain MBP. This derivative, Me2(asym)Arg, was also absent from MBP embedded in the most compact multilamellar myelin, but was present in MBP in the least compact myelin (P3B). Comparing the extent of total methylation in vivo (sum of all three arginine derivatives), MBP extracted from less-compact myelin (P3A and P3B) showed a level approx. 40% higher than that from compact myelin. MBPs isolated from dysmyelinating mutant mouse brains, such as jimpy (jp/y) and quaking (qk/qk), contained a much higher level of Me2(asym)Arg relative to the other two methyl derivatives and also in comparison with those levels in the mother brain MBP. SDS/PAGE analysis of MBPs extracted from the mutant (both jp/y and qk/qk) as well as young normal (6-13 days old) mouse brains indicated the presence of a high-molecular-mass isoform of MBP (about 32 kDa), but this isoform was not found in adult brains. These results therefore indicate that structural integrity of myelin membrane in which MBP is embedded appears to play a pivotal role in determining the extent and the kind of Me2Arg formation in MBP at the post-translational level.", "contents": "Studies on NG-methylarginine derivatives in myelin basic protein from developing and mutant mouse brain. The amounts of NG-methylarginine derivatives in myelin basic protein (MBP) purified from dysmyelinating mutant and different stages of normal myelinating mouse brains have been studied by using h.p.l.c. with a highly sensitive post-column o-phthaldialdehyde derivative-formation method. All three naturally occurring derivatives (NG-monomethylarginine (MeArg), NGN'G-dimethylarginine [Me2(sym)Arg] and NGNG-dimethylarginine [Me2(asym)Arg]) were found in MBP; however, their relative concentrations varied significantly with the age of the animal. The amounts of MeArg and Me2(sym)Arg in MBP increased as a function of the age of the brain, whereas that of Me2(asym)Arg decreased. MBP from early-myelinating mouse brain was shown to contain a high proportion of Me2(asym)Arg, which was hardly detectable in older brain MBP. This derivative, Me2(asym)Arg, was also absent from MBP embedded in the most compact multilamellar myelin, but was present in MBP in the least compact myelin (P3B). Comparing the extent of total methylation in vivo (sum of all three arginine derivatives), MBP extracted from less-compact myelin (P3A and P3B) showed a level approx. 40% higher than that from compact myelin. MBPs isolated from dysmyelinating mutant mouse brains, such as jimpy (jp/y) and quaking (qk/qk), contained a much higher level of Me2(asym)Arg relative to the other two methyl derivatives and also in comparison with those levels in the mother brain MBP. SDS/PAGE analysis of MBPs extracted from the mutant (both jp/y and qk/qk) as well as young normal (6-13 days old) mouse brains indicated the presence of a high-molecular-mass isoform of MBP (about 32 kDa), but this isoform was not found in adult brains. These results therefore indicate that structural integrity of myelin membrane in which MBP is embedded appears to play a pivotal role in determining the extent and the kind of Me2Arg formation in MBP at the post-translational level."} {"id": "PMID:1280108", "title": "Purification and biochemical characterization of non-myristoylated recombinant pp60c-src kinase.", "content": "To obtain sufficient material for the biochemical and biophysical study of pp60c-src, we have utilized a recombinant pp60c-src baculovirus lacking the myristoylation site at codon 2. On infection of Sf9 cells, this virus produced large amounts of soluble non-myristoylated pp60c-src. The use of non-myristoylated pp60c-src (1) increases production of pp60c-src compared with the wild-type protein, (2) facilitates purification, (3) yields a stable product and (4) allows biochemical studies in the absence of detergents. Up to 20 mg of pp60c-src of greater than 95% purity has been purified from 6 litres of Sf9 cells grown in a bioreactor. One major and multiple minor forms of pp60c-src were separated by Mono Q f.p.l.c. Isoelectric focusing of purified pp60c-src species revealed heterogeneity, some of which could be attributed to differences in the tyrosine phosphorylation state of the enzyme. Kinetic analysis of non-myristoylated pp60c-src kinase in the presence of Mg2+ gave Km values for angiotensin II and ATP of 2 mM and 30 microM respectively and a Vmax. of 620 nmol/min per mg. The kinetic constants and metal ion preferences of a number of copolymers and peptide substrates have been compared. Polylysine and poly(GLAT), which was not phosphorylated by the pp60c-src kinase, dramatically activated autophosphorylation of Tyr-416, suggesting a conformation modulation of pp60c-src by charged polymers. This finding implies that Tyr-527 dephosphorylation is not sufficient for full activation of pp60c-src in vitro.", "contents": "Purification and biochemical characterization of non-myristoylated recombinant pp60c-src kinase. To obtain sufficient material for the biochemical and biophysical study of pp60c-src, we have utilized a recombinant pp60c-src baculovirus lacking the myristoylation site at codon 2. On infection of Sf9 cells, this virus produced large amounts of soluble non-myristoylated pp60c-src. The use of non-myristoylated pp60c-src (1) increases production of pp60c-src compared with the wild-type protein, (2) facilitates purification, (3) yields a stable product and (4) allows biochemical studies in the absence of detergents. Up to 20 mg of pp60c-src of greater than 95% purity has been purified from 6 litres of Sf9 cells grown in a bioreactor. One major and multiple minor forms of pp60c-src were separated by Mono Q f.p.l.c. Isoelectric focusing of purified pp60c-src species revealed heterogeneity, some of which could be attributed to differences in the tyrosine phosphorylation state of the enzyme. Kinetic analysis of non-myristoylated pp60c-src kinase in the presence of Mg2+ gave Km values for angiotensin II and ATP of 2 mM and 30 microM respectively and a Vmax. of 620 nmol/min per mg. The kinetic constants and metal ion preferences of a number of copolymers and peptide substrates have been compared. Polylysine and poly(GLAT), which was not phosphorylated by the pp60c-src kinase, dramatically activated autophosphorylation of Tyr-416, suggesting a conformation modulation of pp60c-src by charged polymers. This finding implies that Tyr-527 dephosphorylation is not sufficient for full activation of pp60c-src in vitro."} {"id": "PMID:1280109", "title": "Brain nitric oxide synthase is a haemoprotein.", "content": "Brain nitric oxide (NO) synthase showed pyridine haemochrome spectra typical of ferroprotoporphyrin IX-containing enzymes. The haem content of purified NO synthase was in the range 0.7-0.9 mol/mol of 160 kDa subunit. In the presence of CO, NO, KCN and miconazole, the L-citrulline-forming activity of NO synthase was markedly diminished, demonstrating that enzyme-bound haem is involved in enzymic NO synthesis.", "contents": "Brain nitric oxide synthase is a haemoprotein. Brain nitric oxide (NO) synthase showed pyridine haemochrome spectra typical of ferroprotoporphyrin IX-containing enzymes. The haem content of purified NO synthase was in the range 0.7-0.9 mol/mol of 160 kDa subunit. In the presence of CO, NO, KCN and miconazole, the L-citrulline-forming activity of NO synthase was markedly diminished, demonstrating that enzyme-bound haem is involved in enzymic NO synthesis."} {"id": "PMID:1280110", "title": "A monoclonal anti-peptide antibody reacting with the insulin receptor beta-subunit. Characterization of the antibody and its epitope and use in immunoaffinity purification of intact receptors.", "content": "A mouse monoclonal antibody (CT-1) was prepared against the C-terminal peptide sequence of the human insulin receptor beta-subunit (KKNGRILTLPRSNPS). The antibody reacted with native human and rat insulin receptors in solution, whether or not insulin was bound and whether or not the receptor had undergone prior tyrosine autophosphorylation. The antibody also reacted specifically with the receptor beta-subunit on blots of SDS/polyacrylamide gels. Preincubation of soluble receptors with antibody increased the binding of 125I-insulin approx. 2-fold. The antibody did not affect insulin-stimulated autophosphorylation, but increased the basal autophosphorylation rate approx. 2-fold. The amino acid residues contributing to the epitope for CT-1 were defined by construction and screening of an epitope library. Oligonucleotides containing 23 random bases were synthesized and ligated into the vector pCL627, and the corresponding peptide sequences expressed as fusion proteins in Escherichia coli were screened by colony blotting. Reactive peptides were identified by sequencing the oligonucleotide inserts in plasmids purified from positive colonies. Six different positive sequences were found after 900,000 colonies had been screened, and the consensus epitope was identified as GRVLTLPRS. Phosphorylation of the threonine residue within this sequence (corresponding to the known phosphorylation site Thr-1348 in the insulin receptor) decreased the affinity of antibody binding approx. 100-fold, as measured by competition in an e.l.i.s.a. Antibody CT-1 was used for immunoaffinity isolation of insulin receptor from detergent-solubilized human placental or rat liver microsomal membranes. Highly purified receptor was obtained in 60% yield by binding to CT-1-Sepharose immunoadsorbent and specific elution with a solution of peptide corresponding to the known epitope. This approach to purification under very mild conditions may in principle be used with any protein for which an antibody is available and for which a peptide epitope or 'mimotope' can be identified.", "contents": "A monoclonal anti-peptide antibody reacting with the insulin receptor beta-subunit. Characterization of the antibody and its epitope and use in immunoaffinity purification of intact receptors. A mouse monoclonal antibody (CT-1) was prepared against the C-terminal peptide sequence of the human insulin receptor beta-subunit (KKNGRILTLPRSNPS). The antibody reacted with native human and rat insulin receptors in solution, whether or not insulin was bound and whether or not the receptor had undergone prior tyrosine autophosphorylation. The antibody also reacted specifically with the receptor beta-subunit on blots of SDS/polyacrylamide gels. Preincubation of soluble receptors with antibody increased the binding of 125I-insulin approx. 2-fold. The antibody did not affect insulin-stimulated autophosphorylation, but increased the basal autophosphorylation rate approx. 2-fold. The amino acid residues contributing to the epitope for CT-1 were defined by construction and screening of an epitope library. Oligonucleotides containing 23 random bases were synthesized and ligated into the vector pCL627, and the corresponding peptide sequences expressed as fusion proteins in Escherichia coli were screened by colony blotting. Reactive peptides were identified by sequencing the oligonucleotide inserts in plasmids purified from positive colonies. Six different positive sequences were found after 900,000 colonies had been screened, and the consensus epitope was identified as GRVLTLPRS. Phosphorylation of the threonine residue within this sequence (corresponding to the known phosphorylation site Thr-1348 in the insulin receptor) decreased the affinity of antibody binding approx. 100-fold, as measured by competition in an e.l.i.s.a. Antibody CT-1 was used for immunoaffinity isolation of insulin receptor from detergent-solubilized human placental or rat liver microsomal membranes. Highly purified receptor was obtained in 60% yield by binding to CT-1-Sepharose immunoadsorbent and specific elution with a solution of peptide corresponding to the known epitope. This approach to purification under very mild conditions may in principle be used with any protein for which an antibody is available and for which a peptide epitope or 'mimotope' can be identified."} {"id": "PMID:1280111", "title": "Studies on epitopes on low-density lipoprotein modified by 4-hydroxynonenal. Biochemical characterization and determination.", "content": "Oxidation of human low-density lipoprotein (LDL) was found to be accompanied by the generation of various reactive aldehydes. One of them, 4-hydroxynonenal (HNE), was shown to modify LDL to a form which represents a good model of oxidized LDL (ox-LDL). In order to investigate the epitopes newly formed on HNE-modified LDL, a polyvalent antiserum to HNE-LDL [anti-(HNE-LDL)] was raised in rabbits and the non-specific components were removed with native LDL coupled to CNBr-Sepharose 4B. Competitive fluorescence immunoassay analysis showed that anti-(HNE-LDL) recognized HNE-LDL, copper-oxidized LDL, HNE-albumin and to a lower extent HNE-modified high-density lipoprotein 3 (HNE-HDL3) and ox-HDL3 but not native LDL. A certain degree of cross-reactivity of the antibody with LDLs modified by either hexanal or 2,4-heptadienal was found. No reaction was obtained with LDL labelled with malondialdehyde. From the abilities of HNE-modified poly(L-amino acids) to compete with HNE-LDL for binding to anti-(HNE-LDL), it is postulated that lysine, tyrosine, arginine and histidine are involved in the formation of HNE-derived epitopes on apolipoprotein B (apo B). Using a double-sandwich fluorescence immunoassay [capture antibody: anti-(apo B); detection antibody: anti-(HNE-LDL)] we found that the HNE-derived epitopes were expressed at a far higher degree in ox-LDL and HNE-LDL than in native LDL.", "contents": "Studies on epitopes on low-density lipoprotein modified by 4-hydroxynonenal. Biochemical characterization and determination. Oxidation of human low-density lipoprotein (LDL) was found to be accompanied by the generation of various reactive aldehydes. One of them, 4-hydroxynonenal (HNE), was shown to modify LDL to a form which represents a good model of oxidized LDL (ox-LDL). In order to investigate the epitopes newly formed on HNE-modified LDL, a polyvalent antiserum to HNE-LDL [anti-(HNE-LDL)] was raised in rabbits and the non-specific components were removed with native LDL coupled to CNBr-Sepharose 4B. Competitive fluorescence immunoassay analysis showed that anti-(HNE-LDL) recognized HNE-LDL, copper-oxidized LDL, HNE-albumin and to a lower extent HNE-modified high-density lipoprotein 3 (HNE-HDL3) and ox-HDL3 but not native LDL. A certain degree of cross-reactivity of the antibody with LDLs modified by either hexanal or 2,4-heptadienal was found. No reaction was obtained with LDL labelled with malondialdehyde. From the abilities of HNE-modified poly(L-amino acids) to compete with HNE-LDL for binding to anti-(HNE-LDL), it is postulated that lysine, tyrosine, arginine and histidine are involved in the formation of HNE-derived epitopes on apolipoprotein B (apo B). Using a double-sandwich fluorescence immunoassay [capture antibody: anti-(apo B); detection antibody: anti-(HNE-LDL)] we found that the HNE-derived epitopes were expressed at a far higher degree in ox-LDL and HNE-LDL than in native LDL."} {"id": "PMID:1280112", "title": "Induction of nitric oxide synthase in L929 cells by tumour-necrosis factor alpha is prevented by inhibitors of poly(ADP-ribose) polymerase.", "content": "The fibroblast cell line L929 contains a constitutively expressed NO synthase (EC 1.14.29.-) activity, which can be increased about 10-fold by tumour-necrosis factor alpha (TNF-alpha). Activities of the constitutive and the inducible enzymes are tetrahydrobiopterin-independent and can be inhibited by L-NG-nitroarginine. Induction of NO synthase by TNF-alpha was prevented by inhibitors of poly(ADP-ribose) polymerase, namely nicotinamide, 3-methoxybenzamide and 3-aminobenzamide. TNF-alpha did not lead to an increase in ADP-ribosyltransferase activity nor to a change in the pattern of ADP-ribosylated proteins. The inhibitors were only active during the first 4-5 h after exposure to TNF-alpha and they were found to suppress synthesis of protein, DNA and RNA. These data suggest that the inhibitors prevent induction of NO synthase by interference with RNA and protein synthesis. It is not yet known which reactions of these biosynthetic processes are affected by the inhibitors.", "contents": "Induction of nitric oxide synthase in L929 cells by tumour-necrosis factor alpha is prevented by inhibitors of poly(ADP-ribose) polymerase. The fibroblast cell line L929 contains a constitutively expressed NO synthase (EC 1.14.29.-) activity, which can be increased about 10-fold by tumour-necrosis factor alpha (TNF-alpha). Activities of the constitutive and the inducible enzymes are tetrahydrobiopterin-independent and can be inhibited by L-NG-nitroarginine. Induction of NO synthase by TNF-alpha was prevented by inhibitors of poly(ADP-ribose) polymerase, namely nicotinamide, 3-methoxybenzamide and 3-aminobenzamide. TNF-alpha did not lead to an increase in ADP-ribosyltransferase activity nor to a change in the pattern of ADP-ribosylated proteins. The inhibitors were only active during the first 4-5 h after exposure to TNF-alpha and they were found to suppress synthesis of protein, DNA and RNA. These data suggest that the inhibitors prevent induction of NO synthase by interference with RNA and protein synthesis. It is not yet known which reactions of these biosynthetic processes are affected by the inhibitors."} {"id": "PMID:1280113", "title": "Molecular identification of the liver- and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction.", "content": "The cDNAs of two types of fatty acid-binding protein (FABP) present in human kidney, previously described as types A and B, were isolated using reverse transcriptase-PCR (RT-PCR) with human kidney mRNA and various sets of primers. The cDNA fragments were cloned and sequenced. Renal FABP type A and B cDNAs appeared to be completely identical to human liver- and heart-type FABP cDNAs respectively. In the second part of this study we demonstrated the presence of liver-type FABP in rat kidney by chromatography, e.l.i.s.a. and immunocytochemistry. The ratio and cellular distribution of the two FABP types varies markedly in human and rat kidney. Using RT-PCR we were also able to prepare and identify liver- and heart-type FABP cDNAs with mRNA from both male and female rat kidney.", "contents": "Molecular identification of the liver- and the heart-type fatty acid-binding proteins in human and rat kidney. Use of the reverse transcriptase polymerase chain reaction. The cDNAs of two types of fatty acid-binding protein (FABP) present in human kidney, previously described as types A and B, were isolated using reverse transcriptase-PCR (RT-PCR) with human kidney mRNA and various sets of primers. The cDNA fragments were cloned and sequenced. Renal FABP type A and B cDNAs appeared to be completely identical to human liver- and heart-type FABP cDNAs respectively. In the second part of this study we demonstrated the presence of liver-type FABP in rat kidney by chromatography, e.l.i.s.a. and immunocytochemistry. The ratio and cellular distribution of the two FABP types varies markedly in human and rat kidney. Using RT-PCR we were also able to prepare and identify liver- and heart-type FABP cDNAs with mRNA from both male and female rat kidney."} {"id": "PMID:1280114", "title": "Gs alpha is a substrate for mono(ADP-ribosyl)transferase of NG108-15 cells. ADP-ribosylation regulates Gs alpha activity and abundance.", "content": "NG108-15 neuroblastoma x glioma somatic hybrid cells were permeabilized in the presence of [32P]NAD+ and then cultured for 18 h. Resolution of the cell proteins on polyacrylamide gels revealed [32P]ADP-ribosylation of five major protein species with molecular mass values of 52 kDa, 44 kDa, 35 kDa, 30 kDa and 25 kDa. A similar pattern of labelling was also seen when NG108-15 cell membranes were incubated with [32P]NAD+ and hydrolysis of the product revealed mono(ADP-ribosyl)ation. Immunoprecipitation of these products with anti-Gs alpha antiserum revealed a single band identical to cholera toxin substrate. Culture of [32P]NAD(+)-loaded cells for 18 h in the presence of 50 mM-nicotinamide inhibited the eukaryotic mono(ADP-ribosyl)transferase activity. Inhibition of the eukaryotic enzyme was also accompanied by an increase in the abundance of Gs alpha, whether measured by Western blotting with anti-Gs alpha antibody (two separate antisera) or by cholera toxin-dependent [32P]ADP-ribosylation. There was no accompanying change in the abundance of G beta. The increase in Gs alpha abundance in nicotinamide-treated NG108-15 cells was accompanied by a 2-fold increase in basal adenylate cyclase activity (measured in the presence of GTP), and by a smaller but significant increase in iloprost-dependent activation of adenylate cyclase. Receptor number or affinity was not affected by nicotinamide, since this treatment did not alter the binding parameters of [3H]iloprost to NG108-15 cell membranes. Short-term exposure of cells to nicotinamide for 1 h revealed no significant difference in either basal or agonist-stimulated adenylate cyclase activity. These results reveal that mono(ADP-ribosyl)ation of Gs alpha by eukaryotic ADP-ribosyltransferase modifies the abundance and activity of Gs alpha in NG108-15 cells, and hence may play a role in the hormonal regulation of cell function.", "contents": "Gs alpha is a substrate for mono(ADP-ribosyl)transferase of NG108-15 cells. ADP-ribosylation regulates Gs alpha activity and abundance. NG108-15 neuroblastoma x glioma somatic hybrid cells were permeabilized in the presence of [32P]NAD+ and then cultured for 18 h. Resolution of the cell proteins on polyacrylamide gels revealed [32P]ADP-ribosylation of five major protein species with molecular mass values of 52 kDa, 44 kDa, 35 kDa, 30 kDa and 25 kDa. A similar pattern of labelling was also seen when NG108-15 cell membranes were incubated with [32P]NAD+ and hydrolysis of the product revealed mono(ADP-ribosyl)ation. Immunoprecipitation of these products with anti-Gs alpha antiserum revealed a single band identical to cholera toxin substrate. Culture of [32P]NAD(+)-loaded cells for 18 h in the presence of 50 mM-nicotinamide inhibited the eukaryotic mono(ADP-ribosyl)transferase activity. Inhibition of the eukaryotic enzyme was also accompanied by an increase in the abundance of Gs alpha, whether measured by Western blotting with anti-Gs alpha antibody (two separate antisera) or by cholera toxin-dependent [32P]ADP-ribosylation. There was no accompanying change in the abundance of G beta. The increase in Gs alpha abundance in nicotinamide-treated NG108-15 cells was accompanied by a 2-fold increase in basal adenylate cyclase activity (measured in the presence of GTP), and by a smaller but significant increase in iloprost-dependent activation of adenylate cyclase. Receptor number or affinity was not affected by nicotinamide, since this treatment did not alter the binding parameters of [3H]iloprost to NG108-15 cell membranes. Short-term exposure of cells to nicotinamide for 1 h revealed no significant difference in either basal or agonist-stimulated adenylate cyclase activity. These results reveal that mono(ADP-ribosyl)ation of Gs alpha by eukaryotic ADP-ribosyltransferase modifies the abundance and activity of Gs alpha in NG108-15 cells, and hence may play a role in the hormonal regulation of cell function."} {"id": "PMID:1280115", "title": "The inhibitory GTP-binding protein (Gi) regulates the agonistic property of beta-adrenergic ligands in isolated rat adipocytes. Evidence for a priming effect of cyclic AMP.", "content": "Prenalterol, an allegedly beta 1-selective adrenergic agonist with high intrinsic sympathomimetic activity (ISA), was shown to be weakly lipolytic in rat adipocytes. However, in pertussis-toxin-treated adipocytes, the ISA of prenalterol was markedly increased (from 10-20% to approx. 100% of that of isoprenaline). The cellular sensitivity was also increased (EC50 approx. 60 nM and approx. 3 microM in pertussis-toxin-treated and control cells respectively). A similar effect was seen for other partial agonists such as the beta 2-selective agonist terbutaline and for beta-adrenergic antagonists with some intrinsic activity (metoprolol, pindolol). There was no clear change in sensitivity to isoprenaline's ability to stimulate adenylate cyclase in adipocyte membranes from pertussis-toxin-treated animals but the cyclase activity was increased approx. 4-fold in the presence of 1 microM-GTP. Prenalterol stimulated lipolysis by only small increases in intracellular cyclic AMP (cAMP) levels (less than 10% of that seen with isoprenaline). Basal lipolysis was increased in cells from pertussis-toxin-treated rats and the cellular sensitivity to the non-degradable cAMP analogue, N6-monobutyryl-cAMP, was increased. In control cells, a submaximal concentration of prenalterol (0.1 microM) increased the sensitivity to the cAMP analogues, N6-monobutyryl-cAMP and 8-bromo-cAMP. A low concentration (1 mM) of 8-bromo-cAMP also increased the effect of prenalterol. Similar effects were seen when the phosphodiesterase was inhibited. Thus (1) lipolysis is extremely sensitive to small increases in intracellular cAMP; (2) the degree of activation of adenylate cyclase and thus cAMP formation is the rate-limiting step for the biological response of partial agonists; (3) the inhibitory GTP-binding protein, Gi, is an important modulator ('tissue factor') of the beta-adrenergic agonistic property; (4) low levels of cAMP exert a priming effect on protein kinase A.", "contents": "The inhibitory GTP-binding protein (Gi) regulates the agonistic property of beta-adrenergic ligands in isolated rat adipocytes. Evidence for a priming effect of cyclic AMP. Prenalterol, an allegedly beta 1-selective adrenergic agonist with high intrinsic sympathomimetic activity (ISA), was shown to be weakly lipolytic in rat adipocytes. However, in pertussis-toxin-treated adipocytes, the ISA of prenalterol was markedly increased (from 10-20% to approx. 100% of that of isoprenaline). The cellular sensitivity was also increased (EC50 approx. 60 nM and approx. 3 microM in pertussis-toxin-treated and control cells respectively). A similar effect was seen for other partial agonists such as the beta 2-selective agonist terbutaline and for beta-adrenergic antagonists with some intrinsic activity (metoprolol, pindolol). There was no clear change in sensitivity to isoprenaline's ability to stimulate adenylate cyclase in adipocyte membranes from pertussis-toxin-treated animals but the cyclase activity was increased approx. 4-fold in the presence of 1 microM-GTP. Prenalterol stimulated lipolysis by only small increases in intracellular cyclic AMP (cAMP) levels (less than 10% of that seen with isoprenaline). Basal lipolysis was increased in cells from pertussis-toxin-treated rats and the cellular sensitivity to the non-degradable cAMP analogue, N6-monobutyryl-cAMP, was increased. In control cells, a submaximal concentration of prenalterol (0.1 microM) increased the sensitivity to the cAMP analogues, N6-monobutyryl-cAMP and 8-bromo-cAMP. A low concentration (1 mM) of 8-bromo-cAMP also increased the effect of prenalterol. Similar effects were seen when the phosphodiesterase was inhibited. Thus (1) lipolysis is extremely sensitive to small increases in intracellular cAMP; (2) the degree of activation of adenylate cyclase and thus cAMP formation is the rate-limiting step for the biological response of partial agonists; (3) the inhibitory GTP-binding protein, Gi, is an important modulator ('tissue factor') of the beta-adrenergic agonistic property; (4) low levels of cAMP exert a priming effect on protein kinase A."} {"id": "PMID:1280116", "title": "Platelet-derived growth factor AA homodimer stimulates protein synthesis rather than DNA synthesis in vascular smooth muscle cells from spontaneously hypertensive rats but not from normotensive rats.", "content": "Platelet-derived growth factor (PDGF) AB and BB isoforms were potent mitogens for cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). PDGF-AA promotes protein synthesis in a dose-dependent manner in SHR cells, whereas DNA synthesis was stimulated only slightly. However, this isoform did not activate either DNA or protein synthesis in WKY cells. PDGF-AA stimulated tyrosine phosphorylation of its receptor protein and phospholipase C-gamma 1 in SHR cell but not in WKY cells. These results indicate that vascular smooth muscle cell of SHR is uniquely responsive to PDGF-AA, presumably due to abnormality in receptor expression, in its hypertrophic response.", "contents": "Platelet-derived growth factor AA homodimer stimulates protein synthesis rather than DNA synthesis in vascular smooth muscle cells from spontaneously hypertensive rats but not from normotensive rats. Platelet-derived growth factor (PDGF) AB and BB isoforms were potent mitogens for cultured vascular smooth muscle cells from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). PDGF-AA promotes protein synthesis in a dose-dependent manner in SHR cells, whereas DNA synthesis was stimulated only slightly. However, this isoform did not activate either DNA or protein synthesis in WKY cells. PDGF-AA stimulated tyrosine phosphorylation of its receptor protein and phospholipase C-gamma 1 in SHR cell but not in WKY cells. These results indicate that vascular smooth muscle cell of SHR is uniquely responsive to PDGF-AA, presumably due to abnormality in receptor expression, in its hypertrophic response."} {"id": "PMID:1280117", "title": "C-1' hydrogen abstraction of deoxyribose in DNA strand scission by dynemicin A.", "content": "Dynemicin A, which is a hybrid antitumor antibiotic containing anthraquinone and enediyne cores, abstracts the C-1' hydrogen of DNA deoxyribose and then the damaged DNA leads to strand breaks with the formation of 5'- and 3'-phosphate termini. The lesions of C-4' hydrogen also occur at 3' side of G.C base pairs (i. e., 5'-CT and 5'-GA), leading to 5'-phosphate and 3'-phosphoglycolate termini or 4'-hydroxylated abasic sites. The C-1' hydrogen abstraction by dynemicin A is distinct from the preferential C-5' hydrogen abstraction of calicheamicin and neocarzinostatin.", "contents": "C-1' hydrogen abstraction of deoxyribose in DNA strand scission by dynemicin A. Dynemicin A, which is a hybrid antitumor antibiotic containing anthraquinone and enediyne cores, abstracts the C-1' hydrogen of DNA deoxyribose and then the damaged DNA leads to strand breaks with the formation of 5'- and 3'-phosphate termini. The lesions of C-4' hydrogen also occur at 3' side of G.C base pairs (i. e., 5'-CT and 5'-GA), leading to 5'-phosphate and 3'-phosphoglycolate termini or 4'-hydroxylated abasic sites. The C-1' hydrogen abstraction by dynemicin A is distinct from the preferential C-5' hydrogen abstraction of calicheamicin and neocarzinostatin."} {"id": "PMID:1280118", "title": "Calcitonin gene-related peptide stimulates intracellular cAMP via a protein kinase C-controlled mechanism in human ocular ciliary epithelial cells.", "content": "Calcitonin gene-related peptides I and II (CGRP I and II) were found to stimulate cAMP levels by approximately 4-6 fold in human nonpigmented ciliary epithelial cells with half-maximal effective concentrations of 20 x 10(-10) and 3 x 10(-10) M, respectively. Prior exposure of cells to 6 x 10(-7) M phorbol 12-myristate, 13-acetate for 15 min resulted in a 40-50% inhibition of CGRP II-dependent cAMP stimulation. Phorbol didecanoate and dioctanoylglycerol also effectively inhibited, whereas 4 alpha phorbol didecanoate, an ineffective activator of protein kinase C, had no effect. Staurosporine, a protein kinase C inhibitor, blocked the inhibition of cAMP formation by phorbol esters. cAMP stimulation by forskolin or cholera toxin was not inhibited by phorbol esters, suggesting that neither a Gs protein nor adenylyl cyclase is the site of inhibition by protein kinase C. These data therefore suggest that CGRP receptors are required for inhibition of adenylate cyclase by protein kinase C.", "contents": "Calcitonin gene-related peptide stimulates intracellular cAMP via a protein kinase C-controlled mechanism in human ocular ciliary epithelial cells. Calcitonin gene-related peptides I and II (CGRP I and II) were found to stimulate cAMP levels by approximately 4-6 fold in human nonpigmented ciliary epithelial cells with half-maximal effective concentrations of 20 x 10(-10) and 3 x 10(-10) M, respectively. Prior exposure of cells to 6 x 10(-7) M phorbol 12-myristate, 13-acetate for 15 min resulted in a 40-50% inhibition of CGRP II-dependent cAMP stimulation. Phorbol didecanoate and dioctanoylglycerol also effectively inhibited, whereas 4 alpha phorbol didecanoate, an ineffective activator of protein kinase C, had no effect. Staurosporine, a protein kinase C inhibitor, blocked the inhibition of cAMP formation by phorbol esters. cAMP stimulation by forskolin or cholera toxin was not inhibited by phorbol esters, suggesting that neither a Gs protein nor adenylyl cyclase is the site of inhibition by protein kinase C. These data therefore suggest that CGRP receptors are required for inhibition of adenylate cyclase by protein kinase C."} {"id": "PMID:1280119", "title": "Enhancer-site downstream binding protein activity is enriched in rat tissues that express the class I alcohol dehydrogenase gene.", "content": "The activity of the rat class I alcohol dehydrogenase (ADH) is enriched in certain tissues including the liver, intestine and testis. The tissue-specific expression of the gene encoding ADH in the rat was studied and found to closely correlate with tissue isozymic activity. A factor designated enhancer-site downstream binding protein (EDBP) was recently identified in the rat liver and found to interact with the proximal promoter of the class I ADH gene. The distribution of EDBP in nuclear extracts obtained from various tissues was examined based on its sequence-specific DNA binding property and found to correlate with tissue ADH expression. These findings suggest that EDBP is potentially a positive regulatory factor which is involved in controlling the tissue-specific expression of the ADH gene.", "contents": "Enhancer-site downstream binding protein activity is enriched in rat tissues that express the class I alcohol dehydrogenase gene. The activity of the rat class I alcohol dehydrogenase (ADH) is enriched in certain tissues including the liver, intestine and testis. The tissue-specific expression of the gene encoding ADH in the rat was studied and found to closely correlate with tissue isozymic activity. A factor designated enhancer-site downstream binding protein (EDBP) was recently identified in the rat liver and found to interact with the proximal promoter of the class I ADH gene. The distribution of EDBP in nuclear extracts obtained from various tissues was examined based on its sequence-specific DNA binding property and found to correlate with tissue ADH expression. These findings suggest that EDBP is potentially a positive regulatory factor which is involved in controlling the tissue-specific expression of the ADH gene."} {"id": "PMID:1280120", "title": "cAMP induces up-regulation of ETA receptor mRNA and increases responsiveness to endothelin-1 of rat aortic smooth muscle cells in primary culture.", "content": "The effects of cAMP on the expression of ETA (ET-1 selective type) receptor mRNA and on the response to endothelin-1 (ET-1) were investigated in rat aortic smooth muscle cells in primary culture, using reverse transcription polymerase chain reaction (RT-PCR) and fura-2 microfluorometry of cytosolic Ca2+ concentrations ([Ca2+]i). Incubation of the smooth muscle cells with 10 microM forskolin and 10 microM 3-isobutyl-1-methyl-xanthine (IBMX) induced an increase in ETA receptor mRNA by 420% of control after 24 hours. ET-1 induced a biphasic increase in [Ca2+]i, first transient and second sustained phases. Incubation of the smooth muscle cells with forskolin and IBMX for 24 hours increased the [Ca2+]i response by 849% in the first phase and 286% in the second phase, compared with time-matched controls. From these results, we conclude that cAMP induces an up-regulation of the ETA receptor mRNA and increases responsiveness to ET-1 of rat aortic smooth muscle cells in primary culture.", "contents": "cAMP induces up-regulation of ETA receptor mRNA and increases responsiveness to endothelin-1 of rat aortic smooth muscle cells in primary culture. The effects of cAMP on the expression of ETA (ET-1 selective type) receptor mRNA and on the response to endothelin-1 (ET-1) were investigated in rat aortic smooth muscle cells in primary culture, using reverse transcription polymerase chain reaction (RT-PCR) and fura-2 microfluorometry of cytosolic Ca2+ concentrations ([Ca2+]i). Incubation of the smooth muscle cells with 10 microM forskolin and 10 microM 3-isobutyl-1-methyl-xanthine (IBMX) induced an increase in ETA receptor mRNA by 420% of control after 24 hours. ET-1 induced a biphasic increase in [Ca2+]i, first transient and second sustained phases. Incubation of the smooth muscle cells with forskolin and IBMX for 24 hours increased the [Ca2+]i response by 849% in the first phase and 286% in the second phase, compared with time-matched controls. From these results, we conclude that cAMP induces an up-regulation of the ETA receptor mRNA and increases responsiveness to ET-1 of rat aortic smooth muscle cells in primary culture."} {"id": "PMID:1280121", "title": "The glycoprotease of Pasteurella haemolytica A1 eliminates binding of myeloid cells to P-selectin but not to E-selectin.", "content": "HL-60 cells and neutrophils treated with the glycoprotease from Pasteurella haemolytica A1, an enzyme which is specific for O-sialoglycoproteins, were found to be incapable of binding P-selectin but still bound E-selectin. Comparative analysis of [35-S] cysteine labeled proteins from HL-60 cells by 2-dimensional electrophoresis indicated that two major proteins with M(r) 100 and 115 kd were significantly removed from cells which had been treated.", "contents": "The glycoprotease of Pasteurella haemolytica A1 eliminates binding of myeloid cells to P-selectin but not to E-selectin. HL-60 cells and neutrophils treated with the glycoprotease from Pasteurella haemolytica A1, an enzyme which is specific for O-sialoglycoproteins, were found to be incapable of binding P-selectin but still bound E-selectin. Comparative analysis of [35-S] cysteine labeled proteins from HL-60 cells by 2-dimensional electrophoresis indicated that two major proteins with M(r) 100 and 115 kd were significantly removed from cells which had been treated."} {"id": "PMID:1280122", "title": "Post-transcriptional regulation of the pro alpha 1(I) collagen gene in pro alpha 1(I)-deficient, chemically transformed Syrian hamster embryo fibroblasts.", "content": "4-Nitroquinoline-1-oxide-transformed Syrian hamster embryo fibroblasts (NQT-SHE) synthesize the pro alpha 2 chain but not the pro alpha 1 subunit of type I procollagen, and they contain little pro alpha 1(I)mRNA. This study shows that there was no accumulation of pro alpha 1(I) poly(A)+ mRNA in NQT-SHE fibroblasts. BHK cells, a normal established line of hamster fibroblasts that synthesized collagen at approximately the same rate as NQT-SHE fibroblasts, nevertheless produced both subunits of type I collagen and contained pro alpha 1(I)mRNA. Run-off transcription assays with isolated nuclei showed that both the pro alpha 1(I) and pro alpha 2(I) genes were transcribed at about the same rate in NQT-SHE cells as well as in the normal BHK cells. These results suggest that a post-transcriptional defect, probably resulting from transformation, prevents the accumulation of pro alpha 1(I)mRNA in NQT-SHE cells.", "contents": "Post-transcriptional regulation of the pro alpha 1(I) collagen gene in pro alpha 1(I)-deficient, chemically transformed Syrian hamster embryo fibroblasts. 4-Nitroquinoline-1-oxide-transformed Syrian hamster embryo fibroblasts (NQT-SHE) synthesize the pro alpha 2 chain but not the pro alpha 1 subunit of type I procollagen, and they contain little pro alpha 1(I)mRNA. This study shows that there was no accumulation of pro alpha 1(I) poly(A)+ mRNA in NQT-SHE fibroblasts. BHK cells, a normal established line of hamster fibroblasts that synthesized collagen at approximately the same rate as NQT-SHE fibroblasts, nevertheless produced both subunits of type I collagen and contained pro alpha 1(I)mRNA. Run-off transcription assays with isolated nuclei showed that both the pro alpha 1(I) and pro alpha 2(I) genes were transcribed at about the same rate in NQT-SHE cells as well as in the normal BHK cells. These results suggest that a post-transcriptional defect, probably resulting from transformation, prevents the accumulation of pro alpha 1(I)mRNA in NQT-SHE cells."} {"id": "PMID:1280123", "title": "Functional expression of the bradykinin-B2 receptor cDNA in Chinese hamster lung CCL39 fibroblasts.", "content": "The bradykinin (BK) B2 receptor cDNA was synthesized by rt-PCR and transfected into the Chinese hamster lung fibroblasts, CCL39. The CCL39 do not contain the mRNA for this receptor and do not bind BK. Clones of transfected cells were screened for BK receptor mRNA, binding of BK, and for [Ca2+]i response to BK. The clones showed various levels of receptor mRNA. Scatchard analysis of three clones, B6, B5 and B1, each gave a Kd of approximately 1.0nM while the Bmax for each clone differed at 320, 38.7, and 5.39 fmoles per 10(6) cells respectively. The [Ca2+]i response of the three clones to BK decreased with the receptor number/cell. Thus, levels of mRNA, BK binding and [Ca2+]i response proved proportionally related in the transfected clones. The actions of BK and alpha-thrombin, which has an endogenous receptor in these cells, were assessed in clone B6. BK proved active but also distinct from thrombin. BK at 10nM and thrombin at 2units/ml both effectively increased cytosolic [Ca2+]i. BK at 10nM stimulated PGE2 production three fold over basal, while thrombin only marginally elevated PGE2 levels. Alone, BK stimulated a small increase in 3H-thymidine incorporation into DNA. However, in combination with insulin, BK stimulated DNA synthesis to 76% of thrombin, a potent mitogen in these cells. These results illustrate that the BK-B2 receptor cDNA can be stably transfected into a mammalian cell and can activate transmembrane signalling pathways.", "contents": "Functional expression of the bradykinin-B2 receptor cDNA in Chinese hamster lung CCL39 fibroblasts. The bradykinin (BK) B2 receptor cDNA was synthesized by rt-PCR and transfected into the Chinese hamster lung fibroblasts, CCL39. The CCL39 do not contain the mRNA for this receptor and do not bind BK. Clones of transfected cells were screened for BK receptor mRNA, binding of BK, and for [Ca2+]i response to BK. The clones showed various levels of receptor mRNA. Scatchard analysis of three clones, B6, B5 and B1, each gave a Kd of approximately 1.0nM while the Bmax for each clone differed at 320, 38.7, and 5.39 fmoles per 10(6) cells respectively. The [Ca2+]i response of the three clones to BK decreased with the receptor number/cell. Thus, levels of mRNA, BK binding and [Ca2+]i response proved proportionally related in the transfected clones. The actions of BK and alpha-thrombin, which has an endogenous receptor in these cells, were assessed in clone B6. BK proved active but also distinct from thrombin. BK at 10nM and thrombin at 2units/ml both effectively increased cytosolic [Ca2+]i. BK at 10nM stimulated PGE2 production three fold over basal, while thrombin only marginally elevated PGE2 levels. Alone, BK stimulated a small increase in 3H-thymidine incorporation into DNA. However, in combination with insulin, BK stimulated DNA synthesis to 76% of thrombin, a potent mitogen in these cells. These results illustrate that the BK-B2 receptor cDNA can be stably transfected into a mammalian cell and can activate transmembrane signalling pathways."} {"id": "PMID:1280124", "title": "Specific repression of transthyretin gene expression in rat liver by a peroxisome proliferator clofibrate.", "content": "The effect of clofibrate, a hypolipidemic drug and a potent peroxisome proliferator, on expression of a nonperoxisomal transthyretin (prealbumin) gene was studied using rats fed clofibrate for various periods. Upon feeding a diet containing clofibrate, the level of transthyretin mRNA was down-regulated, reaching 20% of the control level, in an almost reciprocal time course to that of increases in the levels of peroxisomal mRNAs. Studies on expression of other steroid hormone regulated genes suggest that clofibrate may down-regulate several but not all types of steroid hormone regulated mRNA expression.", "contents": "Specific repression of transthyretin gene expression in rat liver by a peroxisome proliferator clofibrate. The effect of clofibrate, a hypolipidemic drug and a potent peroxisome proliferator, on expression of a nonperoxisomal transthyretin (prealbumin) gene was studied using rats fed clofibrate for various periods. Upon feeding a diet containing clofibrate, the level of transthyretin mRNA was down-regulated, reaching 20% of the control level, in an almost reciprocal time course to that of increases in the levels of peroxisomal mRNAs. Studies on expression of other steroid hormone regulated genes suggest that clofibrate may down-regulate several but not all types of steroid hormone regulated mRNA expression."} {"id": "PMID:1280125", "title": "Omeprazole, an inducer of human CYP1A1 and 1A2, is not a ligand for the Ah receptor.", "content": "Omeprazole is a benzimidazole derivative which induces both P450 1A1 and 1A2 in human liver in vitro and in vivo. Northern blot analysis of polyA RNA prepared from primary cultures of human hepatocytes indicates that both 1A1 and 1A2 messages are induced by beta-naphthoflavone and omeprazole. Co-treatment of cells with these inducers and with actinomycin D or cycloheximide results in no accumulation of both mRNA or superinduction of 1A1 mRNA, respectively. 9S enriched fraction of cytosol was prepared either from human hepatocytes in culture or from human liver tissue and analyzed by sucrose density gradient sedimentation for its capacity to bind 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole or omeprazole sulfone (a metabolite of omeprazole in man). Whereas 2 microM TCDD displaced almost totally [3H]TCDD from the Ah receptor, both omeprazole and omeprazole sulfone did not, even at 5000-fold molar excess. In addition, when [14C] omeprazole was incubated with 9S enriched fraction of human liver or hepatocyte cytosol, no interaction could be detected in sucrose density gradient. These experiments suggest that omeprazole is not a ligand for the human liver Ah receptor.", "contents": "Omeprazole, an inducer of human CYP1A1 and 1A2, is not a ligand for the Ah receptor. Omeprazole is a benzimidazole derivative which induces both P450 1A1 and 1A2 in human liver in vitro and in vivo. Northern blot analysis of polyA RNA prepared from primary cultures of human hepatocytes indicates that both 1A1 and 1A2 messages are induced by beta-naphthoflavone and omeprazole. Co-treatment of cells with these inducers and with actinomycin D or cycloheximide results in no accumulation of both mRNA or superinduction of 1A1 mRNA, respectively. 9S enriched fraction of cytosol was prepared either from human hepatocytes in culture or from human liver tissue and analyzed by sucrose density gradient sedimentation for its capacity to bind 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), omeprazole or omeprazole sulfone (a metabolite of omeprazole in man). Whereas 2 microM TCDD displaced almost totally [3H]TCDD from the Ah receptor, both omeprazole and omeprazole sulfone did not, even at 5000-fold molar excess. In addition, when [14C] omeprazole was incubated with 9S enriched fraction of human liver or hepatocyte cytosol, no interaction could be detected in sucrose density gradient. These experiments suggest that omeprazole is not a ligand for the human liver Ah receptor."} {"id": "PMID:1280126", "title": "Cloning of two different 5' untranslated exons of bovine acidic fibroblast growth factor by the single strand ligation to single-stranded cDNA methodology.", "content": "In an attempt to characterize the 5' UTR of the aFGF mRNAs we used the new anchored PCR methodology, single strand ligation to ss-cDNAs (SLIC). In bovine brain and retina, two kinds of aFGF cDNA clones were isolated. They contained two alternative exons located 34 bp upstream to the translation initiation codon ATG. Taking into account the number of clones specific for each exon, the two mRNAs are expressed with the same ratio in both tissues. One of these bovine 5' UTR exons (136 bp) showed 81% identity to a human 5' UTR exon, the second one (323 bp) was 70% identical to the second human 5' UTR exon with a central region of 90 nucleotides showing 41% identity. The conservation of the splicing positions for these 5' UTR alternate exons in both bovine and human species, suggests that the overall structure of the aFGF gene is conserved in mammals. Furthermore, the conservation of the nucleotide sequences and of the localization of these 5' UTR exons suggests that these non-coding regions may be involved in the control of aFGF gene expression.", "contents": "Cloning of two different 5' untranslated exons of bovine acidic fibroblast growth factor by the single strand ligation to single-stranded cDNA methodology. In an attempt to characterize the 5' UTR of the aFGF mRNAs we used the new anchored PCR methodology, single strand ligation to ss-cDNAs (SLIC). In bovine brain and retina, two kinds of aFGF cDNA clones were isolated. They contained two alternative exons located 34 bp upstream to the translation initiation codon ATG. Taking into account the number of clones specific for each exon, the two mRNAs are expressed with the same ratio in both tissues. One of these bovine 5' UTR exons (136 bp) showed 81% identity to a human 5' UTR exon, the second one (323 bp) was 70% identical to the second human 5' UTR exon with a central region of 90 nucleotides showing 41% identity. The conservation of the splicing positions for these 5' UTR alternate exons in both bovine and human species, suggests that the overall structure of the aFGF gene is conserved in mammals. Furthermore, the conservation of the nucleotide sequences and of the localization of these 5' UTR exons suggests that these non-coding regions may be involved in the control of aFGF gene expression."} {"id": "PMID:1280127", "title": "The neurofibromatosis 1 gene transcripts expressed in peripheral nerve and neurofibromas bear the additional exon located in the GAP domain.", "content": "A second NF1 messenger differing in the GAP domain was recently described. This type II transcript contains an internal additional sequence consisting of an open reading frame, in phase with the preceding and the following sequences and predicts a 21 amino acid addition in the catalytic domain of NF1 protein. In this report we present analysis of the two forms of NF1 transcripts in several normal human tissues and in primary neurofibromatosis tumors. Our results indicate (i) that the type II NF1 messenger displaying the additional exon is very widely expressed in all the normal adult tissues tested, (ii) that it is the form of NF1 messenger expressed in peripheral nerve and neurofibromas, and (iii) that the additional sequence could encode for a peptide related to a nucleoside triphosphatase.", "contents": "The neurofibromatosis 1 gene transcripts expressed in peripheral nerve and neurofibromas bear the additional exon located in the GAP domain. A second NF1 messenger differing in the GAP domain was recently described. This type II transcript contains an internal additional sequence consisting of an open reading frame, in phase with the preceding and the following sequences and predicts a 21 amino acid addition in the catalytic domain of NF1 protein. In this report we present analysis of the two forms of NF1 transcripts in several normal human tissues and in primary neurofibromatosis tumors. Our results indicate (i) that the type II NF1 messenger displaying the additional exon is very widely expressed in all the normal adult tissues tested, (ii) that it is the form of NF1 messenger expressed in peripheral nerve and neurofibromas, and (iii) that the additional sequence could encode for a peptide related to a nucleoside triphosphatase."} {"id": "PMID:1280128", "title": "Cytokine-induced phosphorylation of pp100 in FDC-ER cells is at tyrosine residues.", "content": "Using FDC-P1 cells stably transfected with a murine erythropoietin receptor cDNA as a model, we recently have shown that erythropoietin (EPO), IL-3 and GM-CSF each induce the rapid phosphorylation of a common cytosolic target, i.e., a M(r) 100,000 phosphoprotein \"pp100\". Presently, we demonstrate that cytokine-induced phosphorylation of pp100 is primarily at tyrosine residues. This is shown by Western blotting with the anti-phosphotyrosine antibody PY20, and by the resistance of [32P]-pp100 to hydroxide-mediated hydrolysis of phosphates. These data, together with the recent observation by Linnekin et al. that pp100/p97 apparently associates directly with EPO receptors, suggest that pp100 may comprise an immediate common component in the signal transduction pathways of EPO, IL-3, GM-CSF and possibly other type I/II cytokine receptors. Additional analyses suggest that pp100 is distinct from a previously described M(r) 100,000 cytosolic target which is tyrosine phosphorylated in hematopoietic cells upon activation of T-cell receptors.", "contents": "Cytokine-induced phosphorylation of pp100 in FDC-ER cells is at tyrosine residues. Using FDC-P1 cells stably transfected with a murine erythropoietin receptor cDNA as a model, we recently have shown that erythropoietin (EPO), IL-3 and GM-CSF each induce the rapid phosphorylation of a common cytosolic target, i.e., a M(r) 100,000 phosphoprotein \"pp100\". Presently, we demonstrate that cytokine-induced phosphorylation of pp100 is primarily at tyrosine residues. This is shown by Western blotting with the anti-phosphotyrosine antibody PY20, and by the resistance of [32P]-pp100 to hydroxide-mediated hydrolysis of phosphates. These data, together with the recent observation by Linnekin et al. that pp100/p97 apparently associates directly with EPO receptors, suggest that pp100 may comprise an immediate common component in the signal transduction pathways of EPO, IL-3, GM-CSF and possibly other type I/II cytokine receptors. Additional analyses suggest that pp100 is distinct from a previously described M(r) 100,000 cytosolic target which is tyrosine phosphorylated in hematopoietic cells upon activation of T-cell receptors."} {"id": "PMID:1280129", "title": "Regulation of lung endothelin content by the glucocorticosteroid budesonide.", "content": "Intratracheal instillation of Sephadex beads induced a long-lasting inflammation in the rat lung as seen by an increase in lung weights. Repeated instillation enhanced this reaction and increased lung endothelin-1 content 3.5 times. Budesonide given s.c. abolished these effects and even reduced basal endothelin-1 content by 72%. The tissue content of the sensory neuropeptide neurokinin A were unaffected by both treatments. Endothelin has been proposed to play a part in the pathogenesis of bronchial asthma. If it is so, the ability of budesonide to reduce endothelin-1 content could thus be added to the list of beneficial effects of glucocorticosteroids in these conditions.", "contents": "Regulation of lung endothelin content by the glucocorticosteroid budesonide. Intratracheal instillation of Sephadex beads induced a long-lasting inflammation in the rat lung as seen by an increase in lung weights. Repeated instillation enhanced this reaction and increased lung endothelin-1 content 3.5 times. Budesonide given s.c. abolished these effects and even reduced basal endothelin-1 content by 72%. The tissue content of the sensory neuropeptide neurokinin A were unaffected by both treatments. Endothelin has been proposed to play a part in the pathogenesis of bronchial asthma. If it is so, the ability of budesonide to reduce endothelin-1 content could thus be added to the list of beneficial effects of glucocorticosteroids in these conditions."} {"id": "PMID:1280130", "title": "Insulin-like growth factor binding protein-5 gene expression is differentially regulated at a post-transcriptional level in retinoic acid-sensitive and resistant MCF-7 human breast carcinoma cells.", "content": "Insulin-like growth factor binding protein (IGFBP) gene expression and IGFBP secretion were investigated in a retinoic acid (RA)-resistant subline (RROI) of MCF-7 human breast carcinoma cells. Our results demonstrate that RRO-I cells constitutively secrete higher levels of IGFBP-3 and IGFBP-5. In addition, we found that a 5-fold increase in IGFBP-5 mRNA levels observed in RRO-I cells, which eventually leads to a similar increase in the secreted levels of IGFBP-5, was partly due to an increase in the stability of IGFBP-5 mRNA. Actinomycin D and cycloheximide differentially stabilized IGFBP-5 mRNA in MCF-7 cells but not in RRO-I cells, indicating a difference in the control of IGFBP-5 gene regulation at the level of mRNA stability in these cell lines.", "contents": "Insulin-like growth factor binding protein-5 gene expression is differentially regulated at a post-transcriptional level in retinoic acid-sensitive and resistant MCF-7 human breast carcinoma cells. Insulin-like growth factor binding protein (IGFBP) gene expression and IGFBP secretion were investigated in a retinoic acid (RA)-resistant subline (RROI) of MCF-7 human breast carcinoma cells. Our results demonstrate that RRO-I cells constitutively secrete higher levels of IGFBP-3 and IGFBP-5. In addition, we found that a 5-fold increase in IGFBP-5 mRNA levels observed in RRO-I cells, which eventually leads to a similar increase in the secreted levels of IGFBP-5, was partly due to an increase in the stability of IGFBP-5 mRNA. Actinomycin D and cycloheximide differentially stabilized IGFBP-5 mRNA in MCF-7 cells but not in RRO-I cells, indicating a difference in the control of IGFBP-5 gene regulation at the level of mRNA stability in these cell lines."} {"id": "PMID:1280131", "title": "An antibody against a CFTR-derived synthetic peptide, incorporated into living submandibular cells, inhibits beta-adrenergic stimulation of mucin secretion.", "content": "An antibody raised against a peptide in the first nucleotide-binding domain (NBD) of CFTR [1], incorporated into intact rat submandibular acini by hypotonic swelling, inhibited beta-adrenergic stimulated mucin secretion, without affecting cyclic AMP rise. The data are the first to show that a CFTR-antibody-containing cell results in defective stimulation of mucin secretion, as is seen in CF cells, and that this can be reversed by an excessive increase in cyclic AMP.", "contents": "An antibody against a CFTR-derived synthetic peptide, incorporated into living submandibular cells, inhibits beta-adrenergic stimulation of mucin secretion. An antibody raised against a peptide in the first nucleotide-binding domain (NBD) of CFTR [1], incorporated into intact rat submandibular acini by hypotonic swelling, inhibited beta-adrenergic stimulated mucin secretion, without affecting cyclic AMP rise. The data are the first to show that a CFTR-antibody-containing cell results in defective stimulation of mucin secretion, as is seen in CF cells, and that this can be reversed by an excessive increase in cyclic AMP."} {"id": "PMID:1280132", "title": "ATP-induced Ca2+ influx is regulated via a pertussis toxin-sensitive mechanism in a PC12 cell clone.", "content": "A PC12 cell clone that responds to ATP with polyphosphoinositide hydrolysis and with a marked, biphasic intracellular free Ca2+ concentration ([Ca2+]i) response (composed by release from intracellular stores accompanied by stimulated influx from the medium), was pretreated with pertussis toxin. In the pretreated cells the responses induced by ATP were differently modified. Polyphosphoinositide hydrolysis and Ca2+ release were moderately inhibited whereas Ca2+ influx was enhanced. Pharmacological experiments revealed the influx enhancement to be sustained by neither voltage-gated nor second messenger-operated Ca2+ channels. Rather, a channel of the receptor-operated type activated by ATP (P2w receptor) appears to work under the negative control of a pertussis toxin-sensitive G protein, acting presumably by direct interaction with the channel in the plane of the plasma membrane.", "contents": "ATP-induced Ca2+ influx is regulated via a pertussis toxin-sensitive mechanism in a PC12 cell clone. A PC12 cell clone that responds to ATP with polyphosphoinositide hydrolysis and with a marked, biphasic intracellular free Ca2+ concentration ([Ca2+]i) response (composed by release from intracellular stores accompanied by stimulated influx from the medium), was pretreated with pertussis toxin. In the pretreated cells the responses induced by ATP were differently modified. Polyphosphoinositide hydrolysis and Ca2+ release were moderately inhibited whereas Ca2+ influx was enhanced. Pharmacological experiments revealed the influx enhancement to be sustained by neither voltage-gated nor second messenger-operated Ca2+ channels. Rather, a channel of the receptor-operated type activated by ATP (P2w receptor) appears to work under the negative control of a pertussis toxin-sensitive G protein, acting presumably by direct interaction with the channel in the plane of the plasma membrane."} {"id": "PMID:1280133", "title": "Isolation of a cDNA for rat CHIP28 water channel: high mRNA expression in kidney cortex and inner medulla.", "content": "The cDNA coding for the rat CHIP28 water channel was isolated from a kidney library. At the amino acid level, rat CHIP28 is 93% identical to the recently published human protein (1). Expression of rat CHIP28 mRNA was highest in the renal inner medulla, unchanged during antidiuresis and twice the level expressed in outer cortex, with lower expression levels also apparent in parotid gland, urinary bladder and prostate. The evidence suggests that CHIP28 water channels in the ADH-sensitive collecting tubules are identical to those of the ADH-insensitive proximal convoluted tubules and possibly other tissues specialised in fluid transport.", "contents": "Isolation of a cDNA for rat CHIP28 water channel: high mRNA expression in kidney cortex and inner medulla. The cDNA coding for the rat CHIP28 water channel was isolated from a kidney library. At the amino acid level, rat CHIP28 is 93% identical to the recently published human protein (1). Expression of rat CHIP28 mRNA was highest in the renal inner medulla, unchanged during antidiuresis and twice the level expressed in outer cortex, with lower expression levels also apparent in parotid gland, urinary bladder and prostate. The evidence suggests that CHIP28 water channels in the ADH-sensitive collecting tubules are identical to those of the ADH-insensitive proximal convoluted tubules and possibly other tissues specialised in fluid transport."} {"id": "PMID:1280134", "title": "Opposite effect between intercalator and minor groove binding drug on the higher order structure of DNA as is visualized by fluorescence microscopy.", "content": "Fluorescence microscopy is applied to obtain the information on the change of the higher-order structure of giant DNA molecules in an aqueous solution. Using T4 DNA, it becomes clear that ethidium bromide, an intercalator, tends to extend the DNA, whereas minor groove binding drugs such as 4',6-diamidino-2-phenylindole and Hoechst 33258 tend to contract the DNA. These changes of higher-order structure have been quantitatively evaluated as the changes in persistent length together with the change of contour length. It is also confirmed that the persistent length obtained by use of fluorescence microscopy is reliable enough comparing with those reported for the shorter DNA by use of light scattering.", "contents": "Opposite effect between intercalator and minor groove binding drug on the higher order structure of DNA as is visualized by fluorescence microscopy. Fluorescence microscopy is applied to obtain the information on the change of the higher-order structure of giant DNA molecules in an aqueous solution. Using T4 DNA, it becomes clear that ethidium bromide, an intercalator, tends to extend the DNA, whereas minor groove binding drugs such as 4',6-diamidino-2-phenylindole and Hoechst 33258 tend to contract the DNA. These changes of higher-order structure have been quantitatively evaluated as the changes in persistent length together with the change of contour length. It is also confirmed that the persistent length obtained by use of fluorescence microscopy is reliable enough comparing with those reported for the shorter DNA by use of light scattering."} {"id": "PMID:1280135", "title": "Differential regulation of mRNAs encoding three protein-tyrosine phosphatases by insulin and activation of protein kinase C.", "content": "Protein-tyrosine phosphatases (PTPases) play an essential role in the control of signalling through phosphotyrosine pathways. Since little is known about the regulation of these enzymes, we examined the effect of insulin and phorbol 12-myristate 13-acetate (PMA) treatment of well-differentiated rat hepatoma (Fao) cells on the expression of mRNAs encoding three major PTPase homologs in liver: PTPase1B, an intracellular enzyme with a single conserved PTPase domain, and two tandem-domain, transmembrane PTPases, known as LAR and LRP. Treatment of serum-deprived cells with 100 nM insulin increased the abundance of the 4.3 kb and 1.6 kb mRNAs encoding PTPase1B on Northern analysis by 1.6 and 3.1-fold, respectively (p < or = 0.02). Similarly, exposure to 100 ng/ml PMA increased the 4.3 and 1.6 kb PTPase1B mRNAs by 4.5 and 5.7-fold, respectively (p < or = 0.035). In contrast, treatment with insulin or PMA had no significant effect of the abundance of mRNA encoding either LAR or LRP. PMA appeared to have a transcriptional effect on the PTPase1B gene by a protein kinase C-mediated mechanism. The increase in PTPase1B mRNA expression by insulin and PMA suggests that this PTPase may provide feed-back regulation of signalling through the insulin action pathway as well as a potential link between the action of protein kinase C and the regulation of specific phosphotyrosine residues in cells.", "contents": "Differential regulation of mRNAs encoding three protein-tyrosine phosphatases by insulin and activation of protein kinase C. Protein-tyrosine phosphatases (PTPases) play an essential role in the control of signalling through phosphotyrosine pathways. Since little is known about the regulation of these enzymes, we examined the effect of insulin and phorbol 12-myristate 13-acetate (PMA) treatment of well-differentiated rat hepatoma (Fao) cells on the expression of mRNAs encoding three major PTPase homologs in liver: PTPase1B, an intracellular enzyme with a single conserved PTPase domain, and two tandem-domain, transmembrane PTPases, known as LAR and LRP. Treatment of serum-deprived cells with 100 nM insulin increased the abundance of the 4.3 kb and 1.6 kb mRNAs encoding PTPase1B on Northern analysis by 1.6 and 3.1-fold, respectively (p < or = 0.02). Similarly, exposure to 100 ng/ml PMA increased the 4.3 and 1.6 kb PTPase1B mRNAs by 4.5 and 5.7-fold, respectively (p < or = 0.035). In contrast, treatment with insulin or PMA had no significant effect of the abundance of mRNA encoding either LAR or LRP. PMA appeared to have a transcriptional effect on the PTPase1B gene by a protein kinase C-mediated mechanism. The increase in PTPase1B mRNA expression by insulin and PMA suggests that this PTPase may provide feed-back regulation of signalling through the insulin action pathway as well as a potential link between the action of protein kinase C and the regulation of specific phosphotyrosine residues in cells."} {"id": "PMID:1280136", "title": "Potent block of Cl- channels by antiallergic drugs.", "content": "Two antiallergic drugs, cromolyn and RU 31156, were examined for their potency to block intermediate-conductance Cl- channels. For this, single Cl- channel activities of mucosal-type mast cells (RBL-2H3) and alternatively, of colonic carcinoma cells (HT29) were monitored employing the patch-clamp technique in the inside-out patch configuration. Here we show that intermediate-conductance Cl- channels of either cell type were blocked by both compounds. Cl- channel inhibition occurred by a slow rather than a flickering block and with a Hill coefficient around 1. RU 31156 was about one order of magnitude more potent (IC50 about 1 microM) than cromolyn. The IC50 values of each compound were not significantly different (p < 0.01) in the two cell types. Our data provide evidence for two novel Cl- channel blockers, which may be of further use in Cl- channel characterization as well as purification.", "contents": "Potent block of Cl- channels by antiallergic drugs. Two antiallergic drugs, cromolyn and RU 31156, were examined for their potency to block intermediate-conductance Cl- channels. For this, single Cl- channel activities of mucosal-type mast cells (RBL-2H3) and alternatively, of colonic carcinoma cells (HT29) were monitored employing the patch-clamp technique in the inside-out patch configuration. Here we show that intermediate-conductance Cl- channels of either cell type were blocked by both compounds. Cl- channel inhibition occurred by a slow rather than a flickering block and with a Hill coefficient around 1. RU 31156 was about one order of magnitude more potent (IC50 about 1 microM) than cromolyn. The IC50 values of each compound were not significantly different (p < 0.01) in the two cell types. Our data provide evidence for two novel Cl- channel blockers, which may be of further use in Cl- channel characterization as well as purification."} {"id": "PMID:1280137", "title": "Analysis of endogenous and exogenous nuclear translocation of fibroblast growth factor-1 in NIH 3T3 cells.", "content": "Nuclear localization of fibroblast growth factors (FGF) have been reported by many laboratories. We demonstrate here that FGF-1, the precursor for acidic FGF contains a putative nuclear translocation sequence (NTS) NYKKPKL, which is able to direct the expression of the bacterial beta galactosidase (beta gal) gene to the nucleus of transfected NIH 3T3 cells. However, this NTS is unable to target either FGF-1 itself or a FGF-1-beta gal fusion protein into the nucleus, suggesting that FGF-1 may contain an additional sequence which prevents endogenously expressed FGF-1 from being translocated into the nucleus. Indeed, when FGF-1 was fused to the NTS derived from the yeast histone 2B gene, the chimeric construct also failed to be transported into the nucleus either by itself or as a beta gal fusion protein. Interestingly, when 125I-FGF-1 was used to stimulate quiescent NIH 3T3 cells, a significant amount of internalized 125I-FGF-1 (approximately 10%) was found within the nucleus and the nuclear localization of FGF-1 through the exogenous pathway could be significantly reduced by suramin, an inhibitor of the interaction of FGF-1 with its receptor. These data suggest that while FGF-1 contains a NTS, nuclear translocation requires an exogenous and not an endogenous pathway.", "contents": "Analysis of endogenous and exogenous nuclear translocation of fibroblast growth factor-1 in NIH 3T3 cells. Nuclear localization of fibroblast growth factors (FGF) have been reported by many laboratories. We demonstrate here that FGF-1, the precursor for acidic FGF contains a putative nuclear translocation sequence (NTS) NYKKPKL, which is able to direct the expression of the bacterial beta galactosidase (beta gal) gene to the nucleus of transfected NIH 3T3 cells. However, this NTS is unable to target either FGF-1 itself or a FGF-1-beta gal fusion protein into the nucleus, suggesting that FGF-1 may contain an additional sequence which prevents endogenously expressed FGF-1 from being translocated into the nucleus. Indeed, when FGF-1 was fused to the NTS derived from the yeast histone 2B gene, the chimeric construct also failed to be transported into the nucleus either by itself or as a beta gal fusion protein. Interestingly, when 125I-FGF-1 was used to stimulate quiescent NIH 3T3 cells, a significant amount of internalized 125I-FGF-1 (approximately 10%) was found within the nucleus and the nuclear localization of FGF-1 through the exogenous pathway could be significantly reduced by suramin, an inhibitor of the interaction of FGF-1 with its receptor. These data suggest that while FGF-1 contains a NTS, nuclear translocation requires an exogenous and not an endogenous pathway."} {"id": "PMID:1280138", "title": "Changes in serum lipids and lipoproteins in calcium oxalate stone forming rats treated with sodium pentosan polysulphate.", "content": "Sodium pentosan polysulphate (SPP) is reported to influence lipid metabolism, and since a relationship between lipids and stone disorder has been recognised, it was thought worthwhile to study the role of SPP in relation to serum lipids and lipoproteins in experimental calcium oxalate urolithiasis. Serum cholesterol, triglycerides and phospholipids were significantly increased in the glycollate treated group while free fatty acids showed only a mild increase. SPP treatment decreased the cholesterol and triglyceride levels in both controls and stone formers. In contrast, phospholipid and free fatty acid levels were increased in the two groups. In the calculogenic rats, the LDL/HDL cholesterol ratio showed no change, whereas with SPP administration there was a decrease in the treated groups. The observations are suggestive, that SPP treatment may prove beneficial in decreasing the blood lipid levels.", "contents": "Changes in serum lipids and lipoproteins in calcium oxalate stone forming rats treated with sodium pentosan polysulphate. Sodium pentosan polysulphate (SPP) is reported to influence lipid metabolism, and since a relationship between lipids and stone disorder has been recognised, it was thought worthwhile to study the role of SPP in relation to serum lipids and lipoproteins in experimental calcium oxalate urolithiasis. Serum cholesterol, triglycerides and phospholipids were significantly increased in the glycollate treated group while free fatty acids showed only a mild increase. SPP treatment decreased the cholesterol and triglyceride levels in both controls and stone formers. In contrast, phospholipid and free fatty acid levels were increased in the two groups. In the calculogenic rats, the LDL/HDL cholesterol ratio showed no change, whereas with SPP administration there was a decrease in the treated groups. The observations are suggestive, that SPP treatment may prove beneficial in decreasing the blood lipid levels."} {"id": "PMID:1280139", "title": "Noxiustoxin and leiurutoxin III, two homologous peptide toxins with binding properties to synaptosomal membrane K+ channels.", "content": "Noxiustoxin (NTX), a short-chain peptide toxin from the scorpion C. noxius, binds to a single class of non-interacting binding sites in brain synaptosomal membranes with a KD = 160-300 nM and a Bmax = 2.2 pmols.mg-1 protein. The K+ channel blocking agents tetraethylammonium, 4-aminopyridine and Charybdotoxin partially inhibit the binding of [125I]NTX, while a variety of toxins targeted against Ca2+ and Na+ channels have no effect, suggesting that NTX interacts with a bona fide K+ channel protein. NTX totally displaces the binding of [125I]Leiurutoxin III, a novel peptide from L. quinquestriatus venom with N-terminal amino acid sequence homologous to that of NTX. These results suggest that both toxins bind to a common receptor site and are promising tools to dissect the molecular mechanisms of channel-toxin interaction.", "contents": "Noxiustoxin and leiurutoxin III, two homologous peptide toxins with binding properties to synaptosomal membrane K+ channels. Noxiustoxin (NTX), a short-chain peptide toxin from the scorpion C. noxius, binds to a single class of non-interacting binding sites in brain synaptosomal membranes with a KD = 160-300 nM and a Bmax = 2.2 pmols.mg-1 protein. The K+ channel blocking agents tetraethylammonium, 4-aminopyridine and Charybdotoxin partially inhibit the binding of [125I]NTX, while a variety of toxins targeted against Ca2+ and Na+ channels have no effect, suggesting that NTX interacts with a bona fide K+ channel protein. NTX totally displaces the binding of [125I]Leiurutoxin III, a novel peptide from L. quinquestriatus venom with N-terminal amino acid sequence homologous to that of NTX. These results suggest that both toxins bind to a common receptor site and are promising tools to dissect the molecular mechanisms of channel-toxin interaction."} {"id": "PMID:1280140", "title": "Measurement of glycated proteins in human plasma or murine hepatic cytosolic fractions by a competitive enzyme linked immune assay (ELISA).", "content": "After planned immunization, a rabbit polyclonal antibody has been produced that recognized the Schiff base moiety of glycated proteins. Using an ELISA technique, antiserum specifically recognized reduced and glycated epitopes on a variety of proteins, and did not react with nonreduced and glycated proteins. The antiserum showed very low cross-reactivity with reduced but not glycated proteins. The assay was also used to determine the degree of ex vivo glycation of serum proteins from diabetic patients or hepatic cytosolic proteins from mice. Thus, this assay may be used to determine the amount of in vitro or ex vivo glycation of blood or tissue proteins.", "contents": "Measurement of glycated proteins in human plasma or murine hepatic cytosolic fractions by a competitive enzyme linked immune assay (ELISA). After planned immunization, a rabbit polyclonal antibody has been produced that recognized the Schiff base moiety of glycated proteins. Using an ELISA technique, antiserum specifically recognized reduced and glycated epitopes on a variety of proteins, and did not react with nonreduced and glycated proteins. The antiserum showed very low cross-reactivity with reduced but not glycated proteins. The assay was also used to determine the degree of ex vivo glycation of serum proteins from diabetic patients or hepatic cytosolic proteins from mice. Thus, this assay may be used to determine the amount of in vitro or ex vivo glycation of blood or tissue proteins."} {"id": "PMID:1280141", "title": "Doxorubicin inhibits differentiation and enhances expression of the helix-loop-helix genes Id and mTwi in mouse osteoblastic cells.", "content": "Treatment with doxorubicin is associated with decreased levels of expression of muscle-specific genes in myocytes. This may be related to an effect on expression of helix-loop-helix (h-l-h) regulatory molecules since in myoblastic cells, doxorubicin inhibits Myo D expression and enhances Id expression. We have reported that expression of Id and mouse Twist (mTwi), another h-l-h molecule, decline in association with differentiation in osteoblastic cells. We have sought, therefore, to determine the effect of doxorubicin on MC-3T3-E1 osteoblastic cells. Treatment with doxorubicin decreased total cellular protein content, reduced [3H]-leucine incorporation into protein, inhibited proliferation and diminished alkaline phosphatase activity. Glucose utilization and lactate production were not adversely affected. Id expression was increased by doxorubicin treatment under growth conditions but not differentiation conditions. Expression of mTwi was markedly increased under both growth and differentiation conditions. These data support the contention that Id and mTwi may regulate differentiation in osteoblastic cells.", "contents": "Doxorubicin inhibits differentiation and enhances expression of the helix-loop-helix genes Id and mTwi in mouse osteoblastic cells. Treatment with doxorubicin is associated with decreased levels of expression of muscle-specific genes in myocytes. This may be related to an effect on expression of helix-loop-helix (h-l-h) regulatory molecules since in myoblastic cells, doxorubicin inhibits Myo D expression and enhances Id expression. We have reported that expression of Id and mouse Twist (mTwi), another h-l-h molecule, decline in association with differentiation in osteoblastic cells. We have sought, therefore, to determine the effect of doxorubicin on MC-3T3-E1 osteoblastic cells. Treatment with doxorubicin decreased total cellular protein content, reduced [3H]-leucine incorporation into protein, inhibited proliferation and diminished alkaline phosphatase activity. Glucose utilization and lactate production were not adversely affected. Id expression was increased by doxorubicin treatment under growth conditions but not differentiation conditions. Expression of mTwi was markedly increased under both growth and differentiation conditions. These data support the contention that Id and mTwi may regulate differentiation in osteoblastic cells."} {"id": "PMID:1280142", "title": "[A new immunochemical method for detecting substance P receptors based on the biotin-streptavidin system].", "content": "A novel method for detecting the membrane receptors of Substance P (SP) has been developed. The method does not require radioactive derivatives of SP and is based on quantitation of specifically bound biotinylated SP (Bt-SP), the analysis being performed after destruction of the ligand-receptor complex in acidic conditions and Bt-SP extraction into solution. The acidic extract from the Bt-SP-membrane complex after neutralization is added to immulon microELISA plate coated with affinity purified anti-SP-antibodies. The sensitivity of subsequent detection of Bt-SP enhances by using a new type of the streptavidin conjugate with a polymeric form of horseradish peroxidase. Enzyme immunoassay conditions were optimized using [125I]-labelled SP derivative. The developed method allows the determination of femtomoles of SP in a sample and has a sensitivity comparable to that of radioligand analysis.", "contents": "[A new immunochemical method for detecting substance P receptors based on the biotin-streptavidin system]. A novel method for detecting the membrane receptors of Substance P (SP) has been developed. The method does not require radioactive derivatives of SP and is based on quantitation of specifically bound biotinylated SP (Bt-SP), the analysis being performed after destruction of the ligand-receptor complex in acidic conditions and Bt-SP extraction into solution. The acidic extract from the Bt-SP-membrane complex after neutralization is added to immulon microELISA plate coated with affinity purified anti-SP-antibodies. The sensitivity of subsequent detection of Bt-SP enhances by using a new type of the streptavidin conjugate with a polymeric form of horseradish peroxidase. Enzyme immunoassay conditions were optimized using [125I]-labelled SP derivative. The developed method allows the determination of femtomoles of SP in a sample and has a sensitivity comparable to that of radioligand analysis."} {"id": "PMID:1280143", "title": "[Regulation of the catalytic activity and supermolecular structure of penicillin acylase from Escherichia coli in an aerosol OT reversed micelle system in octane].", "content": "The properties of penicillin acylase from E. coli solubilized by hydrated reversed micelles of Aerozol OT (AOT) in octane were studied. The catalytic activity dependence on the hydration degree, a parameter which determines the size of the micelle inner cavity, represents a curve with three optima, each corresponding to the enzyme functioning either in a dimer form (omega 0 = 23) or in the form of separate subunits--heavy, beta, and light, alpha, at omega 0 = 20 and 14, respectively. Reversible dissociation of the enzyme was confirmed by ultracentrifugation followed by electrophoresis. Preparative isolation of penicillin acylase subunits, their catalytic activity being retained, was shown to be possible.", "contents": "[Regulation of the catalytic activity and supermolecular structure of penicillin acylase from Escherichia coli in an aerosol OT reversed micelle system in octane]. The properties of penicillin acylase from E. coli solubilized by hydrated reversed micelles of Aerozol OT (AOT) in octane were studied. The catalytic activity dependence on the hydration degree, a parameter which determines the size of the micelle inner cavity, represents a curve with three optima, each corresponding to the enzyme functioning either in a dimer form (omega 0 = 23) or in the form of separate subunits--heavy, beta, and light, alpha, at omega 0 = 20 and 14, respectively. Reversible dissociation of the enzyme was confirmed by ultracentrifugation followed by electrophoresis. Preparative isolation of penicillin acylase subunits, their catalytic activity being retained, was shown to be possible."} {"id": "PMID:1280144", "title": "Cocaine: an independent risk factor for aortic sudanophilia. A preliminary report.", "content": "Several recent autopsy reports indicate an increased prevalence of coronary atherosclerosis in ischemic heart disease temporally associated with cocaine abuse. The objective of this study was to conduct a retrospective analysis of sudanophilic lesions in young asymptomatic individuals who abused cocaine. Twenty-six cases (15-34-year-old black males) were examined from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Sixteen subjects (mean age 25 +/- 1 years) had a positive toxicologic screen for cocaine and/or its major metabolites at autopsy and were confirmed habitual cocaine abusers. The remaining 10 cases (mean age 24 +/- 2 years) were subjects with a negative toxicologic screen at autopsy and no history of illicit drug abuse. Post-mortem blood was collected for lipoprotein analysis and determination of smoking status. The aorta and right coronary arteries were stained with Sudan IV and the degree and extent of sudanophilia was quantitated by image analysis. Multiple linear regression analysis of cocaine, age, smoking status, VLDL+LDL-C/HDL-C ratio and HDL-C as predictor variables of percentage intimal surface involvement, revealed an association between cocaine abuse and the extent of sudanophilia in both the thoracic and abdominal aorta (P = 0.002 and 0.049, respectively). Analysis of risk factors or of cocaine abuse as predictors of sudanophilia did not achieve statistical significance in the right coronary artery. These preliminary results suggest that habitual use of cocaine, through unknown mechanism(s), increases aortic sudanophilia independent of traditional risk factors.", "contents": "Cocaine: an independent risk factor for aortic sudanophilia. A preliminary report. Several recent autopsy reports indicate an increased prevalence of coronary atherosclerosis in ischemic heart disease temporally associated with cocaine abuse. The objective of this study was to conduct a retrospective analysis of sudanophilic lesions in young asymptomatic individuals who abused cocaine. Twenty-six cases (15-34-year-old black males) were examined from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study. Sixteen subjects (mean age 25 +/- 1 years) had a positive toxicologic screen for cocaine and/or its major metabolites at autopsy and were confirmed habitual cocaine abusers. The remaining 10 cases (mean age 24 +/- 2 years) were subjects with a negative toxicologic screen at autopsy and no history of illicit drug abuse. Post-mortem blood was collected for lipoprotein analysis and determination of smoking status. The aorta and right coronary arteries were stained with Sudan IV and the degree and extent of sudanophilia was quantitated by image analysis. Multiple linear regression analysis of cocaine, age, smoking status, VLDL+LDL-C/HDL-C ratio and HDL-C as predictor variables of percentage intimal surface involvement, revealed an association between cocaine abuse and the extent of sudanophilia in both the thoracic and abdominal aorta (P = 0.002 and 0.049, respectively). Analysis of risk factors or of cocaine abuse as predictors of sudanophilia did not achieve statistical significance in the right coronary artery. These preliminary results suggest that habitual use of cocaine, through unknown mechanism(s), increases aortic sudanophilia independent of traditional risk factors."} {"id": "PMID:1280145", "title": "European comparative clinical study of Inerpan: a new wound dressing in treatment of partial skin thickness burns.", "content": "Eleven European burns centres in five countries (Belgium, England, Germany, Italy, Switzerland) participated in a prospective, randomized clinical trial comparing a new wound dressing Inerpan with conventional dressings such as petroleum jelly gauze, petroleum jelly gauze with antibiotics and silver sulphadiazine cream. The indication was partial skin thickness burns and 62 patients were included. In each patient, two similar lesions (with respect to depth and surface area) were compared, one being treated with Inerpan, the other one with a control dressing. The following parameters were studied: healing time, quality of healing, intensity of pain, local tolerance and frequency of dressing changes. Analysis of the results showed that Inerpan-treated sites healed faster than conventional ones, and were associated with a highly significant reduction of pain. The frequency of dressing changes was greatly reduced and the local tolerance was good.", "contents": "European comparative clinical study of Inerpan: a new wound dressing in treatment of partial skin thickness burns. Eleven European burns centres in five countries (Belgium, England, Germany, Italy, Switzerland) participated in a prospective, randomized clinical trial comparing a new wound dressing Inerpan with conventional dressings such as petroleum jelly gauze, petroleum jelly gauze with antibiotics and silver sulphadiazine cream. The indication was partial skin thickness burns and 62 patients were included. In each patient, two similar lesions (with respect to depth and surface area) were compared, one being treated with Inerpan, the other one with a control dressing. The following parameters were studied: healing time, quality of healing, intensity of pain, local tolerance and frequency of dressing changes. Analysis of the results showed that Inerpan-treated sites healed faster than conventional ones, and were associated with a highly significant reduction of pain. The frequency of dressing changes was greatly reduced and the local tolerance was good."} {"id": "PMID:1280146", "title": "Independent effects of age and nucleus basalis magnocellularis lesion: maze learning, cortical neurochemistry, and morphometry.", "content": "The effects of age and lesion of the cholinergic nucleus basalis magnocellularis (NBm) were assessed behaviorally, morphologically, and biochemically. Groups consisted of rats lesioned 1 month before testing, rats lesioned 13 months before testing, and their respective age-matched controls. Both age and lesion independently induced behavioral deficits in performance on two water maze tasks. The combined effect of these two factors produced behavioral deficits equal to the sum of the individual impairments. NBm lesion produced a 28% decrease in anterior cortical choline acetyltransferase activity and a 20% decrease in synaptophysin immunoreactivity in the neocortex that was stable over a 12-month period. Neither neuritic plaque nor neurofibrillary-tanglelike structures were found in the brains of 18-month-old control rats, nor were they found in NBm-lesioned rats examined 15 months postlesion. There was an age-related decrease in homovanillic acid levels in both control and NBm groups, which suggests a decrease in dopamine turnover. These results show a lack of biochemical and behavioral recovery after NBm lesion and suggest that the effects of age on behavior are independent of NBm-cortical dysfunction.", "contents": "Independent effects of age and nucleus basalis magnocellularis lesion: maze learning, cortical neurochemistry, and morphometry. The effects of age and lesion of the cholinergic nucleus basalis magnocellularis (NBm) were assessed behaviorally, morphologically, and biochemically. Groups consisted of rats lesioned 1 month before testing, rats lesioned 13 months before testing, and their respective age-matched controls. Both age and lesion independently induced behavioral deficits in performance on two water maze tasks. The combined effect of these two factors produced behavioral deficits equal to the sum of the individual impairments. NBm lesion produced a 28% decrease in anterior cortical choline acetyltransferase activity and a 20% decrease in synaptophysin immunoreactivity in the neocortex that was stable over a 12-month period. Neither neuritic plaque nor neurofibrillary-tanglelike structures were found in the brains of 18-month-old control rats, nor were they found in NBm-lesioned rats examined 15 months postlesion. There was an age-related decrease in homovanillic acid levels in both control and NBm groups, which suggests a decrease in dopamine turnover. These results show a lack of biochemical and behavioral recovery after NBm lesion and suggest that the effects of age on behavior are independent of NBm-cortical dysfunction."} {"id": "PMID:1280147", "title": "Direct automated sequencing of 16S rDNA amplified by polymerase chain reaction from bacterial cultures without DNA purification.", "content": "The 16S rRNA gene from various bacterial cultures was amplified by the polymerase chain reaction without DNA purification, and sequenced directly by using a laser fluorescent DNA sequencer and Tth polymerase with a cycle sequencing protocol. The described procedures provide almost complete 16S rDNA sequence data within a couple of days and facilitate systematic studies.", "contents": "Direct automated sequencing of 16S rDNA amplified by polymerase chain reaction from bacterial cultures without DNA purification. The 16S rRNA gene from various bacterial cultures was amplified by the polymerase chain reaction without DNA purification, and sequenced directly by using a laser fluorescent DNA sequencer and Tth polymerase with a cycle sequencing protocol. The described procedures provide almost complete 16S rDNA sequence data within a couple of days and facilitate systematic studies."} {"id": "PMID:1280148", "title": "Immunohistochemical evaluation of the cytoarchitecture of benign and malignant breast lesions.", "content": "Fifty-three breast lesions, which had been fixed in formalin and embedded in paraffin, were immunohistochemically analyzed with monoclonal antibodies to cytokeratin subtypes 1, 5, 10, 14 (34BE12), muscle-specific actins (HHF35) and antiserum to S100 protein, all of which have been used as markers for myoepithelial cells. With these antibodies, a continuous myoepithelial cell layer could generally be seen around the benign ducts and acini. In in situ carcinomas, such a layer could still be observed, though it was usually discontinuous and sometimes absent. In infiltrating carcinomas, no myoepithelial cell layer could be observed. In intraductal hyperplasias, scattered HHF35, 34BE12 and S100-positive cells could be seen amongst the proliferating intraductal cells. In in situ and infiltrating carcinomas, however, such cells could also be observed. This was seen especially with antibodies 34BE12 and S100, and to a lesser extent also with HHF35. Morphologically these cells seemed to belong to the malignant cell population. Although myoepithelial cell preservation is an important morphological parameter in the histological evaluation of breast lesions, the results suggest that the myoepithelial cell markers 34BE12, HHF35 and S100 cannot be used in the differential diagnosis between benign and malignant breast lesions in a straightforward manner. This is because in situ carcinomas have a more or less preserved myoepithelial cell layer, and because many infiltrating and in situ carcinomas contain a subpopulation of neoplastic cells expressing these markers, possibly signifying myoepithelial cell differentiation.", "contents": "Immunohistochemical evaluation of the cytoarchitecture of benign and malignant breast lesions. Fifty-three breast lesions, which had been fixed in formalin and embedded in paraffin, were immunohistochemically analyzed with monoclonal antibodies to cytokeratin subtypes 1, 5, 10, 14 (34BE12), muscle-specific actins (HHF35) and antiserum to S100 protein, all of which have been used as markers for myoepithelial cells. With these antibodies, a continuous myoepithelial cell layer could generally be seen around the benign ducts and acini. In in situ carcinomas, such a layer could still be observed, though it was usually discontinuous and sometimes absent. In infiltrating carcinomas, no myoepithelial cell layer could be observed. In intraductal hyperplasias, scattered HHF35, 34BE12 and S100-positive cells could be seen amongst the proliferating intraductal cells. In in situ and infiltrating carcinomas, however, such cells could also be observed. This was seen especially with antibodies 34BE12 and S100, and to a lesser extent also with HHF35. Morphologically these cells seemed to belong to the malignant cell population. Although myoepithelial cell preservation is an important morphological parameter in the histological evaluation of breast lesions, the results suggest that the myoepithelial cell markers 34BE12, HHF35 and S100 cannot be used in the differential diagnosis between benign and malignant breast lesions in a straightforward manner. This is because in situ carcinomas have a more or less preserved myoepithelial cell layer, and because many infiltrating and in situ carcinomas contain a subpopulation of neoplastic cells expressing these markers, possibly signifying myoepithelial cell differentiation."} {"id": "PMID:1280149", "title": "Immunohistochemical study of 158 lung carcinomas.", "content": "Lung carcinomas were studied immunohistochemically and the results were related to type of tissue sample (bronchoscopic biopsies, surgical specimens, autopsies). All cytokeratins (CAM 5.2, PKK-1, AE1/AE3) reacted with virtually all adenocarcinomas, most squamous, and 65% of the large cell carcinomas, while CAM 5.2 was most efficient with the small cell carcinomas. CEA stained 33% and 60% of the small and large cell carcinomas, respectively, most adenocarcinomas, and 84% of the squamous cell carcinomas, among which staining decreased with dedifferentiation and was often focal. EMA reacted with 90%, and NSE with 20% of all histological types. There was no staining for NF. All antibodies, except EMA, were more efficient with surgical specimens. Our study implies that the cytokeratins we used work better with surgical material, but are generally comparable to monospecific cytokeratin antibodies. Also, EMA is a reliable marker for epithelial differentiation with all types of tissue samples. Moreover, CEA negativity in several poorly differentiated lung carcinomas might have implications in the differential diagnosis against pleural mesothelioma.", "contents": "Immunohistochemical study of 158 lung carcinomas. Lung carcinomas were studied immunohistochemically and the results were related to type of tissue sample (bronchoscopic biopsies, surgical specimens, autopsies). All cytokeratins (CAM 5.2, PKK-1, AE1/AE3) reacted with virtually all adenocarcinomas, most squamous, and 65% of the large cell carcinomas, while CAM 5.2 was most efficient with the small cell carcinomas. CEA stained 33% and 60% of the small and large cell carcinomas, respectively, most adenocarcinomas, and 84% of the squamous cell carcinomas, among which staining decreased with dedifferentiation and was often focal. EMA reacted with 90%, and NSE with 20% of all histological types. There was no staining for NF. All antibodies, except EMA, were more efficient with surgical specimens. Our study implies that the cytokeratins we used work better with surgical material, but are generally comparable to monospecific cytokeratin antibodies. Also, EMA is a reliable marker for epithelial differentiation with all types of tissue samples. Moreover, CEA negativity in several poorly differentiated lung carcinomas might have implications in the differential diagnosis against pleural mesothelioma."} {"id": "PMID:1280150", "title": "Effect of substance P and Sar9Met(O2)11-substance P on cutaneous capillary permeability in guinea pig skin.", "content": "The purpose of this study was to assess the effect of several drugs on the increase in cutaneous capillary permeability induced by intradermal injection of substance P (SP) and Sar9Met(O2)11-SP in guinea pig skin. On the one hand, the increase in cutaneous capillary permeability was partly reduced by spantide, promethazine, atropine or SR 40037, an inhibitor of the angiotensin-converting enzyme. On the other hand, norepinephrine and B3824, a B2-antagonist of bradykinin, showed an enhancing effect. Our results suggest that the effect of SP and Sar9Met(O2)11-SP in guinea pigs is partly mediated by histamine and acetylcholine, and that there is a relationship between tachykinins and bradykinin.", "contents": "Effect of substance P and Sar9Met(O2)11-substance P on cutaneous capillary permeability in guinea pig skin. The purpose of this study was to assess the effect of several drugs on the increase in cutaneous capillary permeability induced by intradermal injection of substance P (SP) and Sar9Met(O2)11-SP in guinea pig skin. On the one hand, the increase in cutaneous capillary permeability was partly reduced by spantide, promethazine, atropine or SR 40037, an inhibitor of the angiotensin-converting enzyme. On the other hand, norepinephrine and B3824, a B2-antagonist of bradykinin, showed an enhancing effect. Our results suggest that the effect of SP and Sar9Met(O2)11-SP in guinea pigs is partly mediated by histamine and acetylcholine, and that there is a relationship between tachykinins and bradykinin."} {"id": "PMID:1280151", "title": "Anticlastogenic effects of 13-cis-retinoic acid in vitro.", "content": "The anticlastogenic effects of 13-cis-retinoic acid were studied in four human lymphoblastoid cell lines and in primary lymphocyte cultures derived from the peripheral blood of 11 study subjects. Cells were pre-incubated with 13-cis-retinoic acid in the concentration range of 10(-8)-10(-5) mol/l for 24 h and the numbers of chromatid breaks per cell induced by bleomycin were determined. The presence of 13-cis-retinoic acid decreased the number of breaks per cell by 13.0 to 59.5% in lymphoblastoid cell lines and by 0 to 57.4% in primary lymphocyte cultures (in the concentration ranges of 10(-8)-10(-6) mol/l and of 10(-8)-10(-5) mol/l, respectively). Regression analysis showed that there was a statistically significant correlation between the presence of 13-cis-retinoic acid and protection against bleomycin-induced clastogenicity. These data give additional information to the knowledge of possible chemopreventive mechanisms of action of 13-cis-retinoic acid.", "contents": "Anticlastogenic effects of 13-cis-retinoic acid in vitro. The anticlastogenic effects of 13-cis-retinoic acid were studied in four human lymphoblastoid cell lines and in primary lymphocyte cultures derived from the peripheral blood of 11 study subjects. Cells were pre-incubated with 13-cis-retinoic acid in the concentration range of 10(-8)-10(-5) mol/l for 24 h and the numbers of chromatid breaks per cell induced by bleomycin were determined. The presence of 13-cis-retinoic acid decreased the number of breaks per cell by 13.0 to 59.5% in lymphoblastoid cell lines and by 0 to 57.4% in primary lymphocyte cultures (in the concentration ranges of 10(-8)-10(-6) mol/l and of 10(-8)-10(-5) mol/l, respectively). Regression analysis showed that there was a statistically significant correlation between the presence of 13-cis-retinoic acid and protection against bleomycin-induced clastogenicity. These data give additional information to the knowledge of possible chemopreventive mechanisms of action of 13-cis-retinoic acid."} {"id": "PMID:1280152", "title": "Phase II study of weekly 4'-epidoxorubicin in patients with metastatic squamous cell cancer of the cervix: an EORTC Gynaecological Cancer Cooperative Group Study.", "content": "In this study 24 patients with metastatic cervical cancer were treated with a weekly bolus injection of 4'-epidoxorubicin at a dose of 12.5 mg/m2. All patients were followed until disease progression. Toxicity was generally absent or very mild. Only 1 patient (4%) had a partial remission lasting 23 weeks and 9 patients (38%) had stable disease with a median duration of 13 weeks (range 7-36). 4'-Epidoxorubicin at this dose and schedule is not active in metastatic squamous cell carcinoma of the cervix.", "contents": "Phase II study of weekly 4'-epidoxorubicin in patients with metastatic squamous cell cancer of the cervix: an EORTC Gynaecological Cancer Cooperative Group Study. In this study 24 patients with metastatic cervical cancer were treated with a weekly bolus injection of 4'-epidoxorubicin at a dose of 12.5 mg/m2. All patients were followed until disease progression. Toxicity was generally absent or very mild. Only 1 patient (4%) had a partial remission lasting 23 weeks and 9 patients (38%) had stable disease with a median duration of 13 weeks (range 7-36). 4'-Epidoxorubicin at this dose and schedule is not active in metastatic squamous cell carcinoma of the cervix."} {"id": "PMID:1280153", "title": "Current status of interferons in the treatment of cancer.", "content": "Interferons produced by recombinant DNA technology began phase I trials little more than a decade ago. Today interferon alfa-2 is a mainstay in the treatment of hairy cell leukemia, and has demonstrated benefit in the more common chronic myelogenous leukemia. Interferon alfa-2 also has activity in other hematologic malignancies, including indolent non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, T-cell lymphoma, and multiple myeloma, and in solid tumors such as disseminated melanoma, renal cell carcinoma, Kaposi's sarcoma, endocrine pancreatic tumors, and malignant carcinoid tumors. Interferon alfa, beta, and gamma remain under investigation to define potential roles in ovarian, breast, bladder, and cervical carcinomas and gliomas. The greatest value of the interferons will be in prolonging the disease-free interval when used in combination with other treatment modalities, including surgery, radiation, chemotherapy, and other biologic agents.", "contents": "Current status of interferons in the treatment of cancer. Interferons produced by recombinant DNA technology began phase I trials little more than a decade ago. Today interferon alfa-2 is a mainstay in the treatment of hairy cell leukemia, and has demonstrated benefit in the more common chronic myelogenous leukemia. Interferon alfa-2 also has activity in other hematologic malignancies, including indolent non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, T-cell lymphoma, and multiple myeloma, and in solid tumors such as disseminated melanoma, renal cell carcinoma, Kaposi's sarcoma, endocrine pancreatic tumors, and malignant carcinoid tumors. Interferon alfa, beta, and gamma remain under investigation to define potential roles in ovarian, breast, bladder, and cervical carcinomas and gliomas. The greatest value of the interferons will be in prolonging the disease-free interval when used in combination with other treatment modalities, including surgery, radiation, chemotherapy, and other biologic agents."} {"id": "PMID:1280154", "title": "Developmental expression of the Drosophila melanogaster calmodulin gene.", "content": "The highly conserved, intracellular calcium binding protein calmodulin is present in all cells at all times. In addition to this constitutive level, the amount of calmodulin is highly regulated according to the tissue or stage of development. Since there are only a few genes or a single gene for this protein in most species, intricate regulatory elements may be necessary to effect its complex regulation. This report adds new information concerning the gene structure and outlines the developmental and spatial regulation of Drosophila melanogaster calmodulin transcripts. The gene contains five exons, including a 49 bp exon in the 5' untranslated region, and spans over 16 kb. Homologues to this small, 5' noncoding exon have not been found in other calmodulin genes. The combined level of the transcripts is developmentally regulated, and the relative amounts of the two transcript size classes (1.65 kb and 1.9 kb) are differentially regulated during development. Primer extension experiments and RNase protection mapping show that both size classes of Drosophila calmodulin transcripts initiate at the same site but undergo alternative termination within the final exon. The spatial distribution of calmodulin transcripts was examined by in situ hybridization to sections of adults and to developmentally staged whole mount embryos. Calmodulin transcripts are evenly distributed early in embryogenesis. In later stages of embryogenesis, higher levels accumulate in the developing nerve cord and other tissues. Elevated levels of calmodulin transcripts are seen quite distinctly in the adult neural tissues and in the photoreceptor region of the compound eye.", "contents": "Developmental expression of the Drosophila melanogaster calmodulin gene. The highly conserved, intracellular calcium binding protein calmodulin is present in all cells at all times. In addition to this constitutive level, the amount of calmodulin is highly regulated according to the tissue or stage of development. Since there are only a few genes or a single gene for this protein in most species, intricate regulatory elements may be necessary to effect its complex regulation. This report adds new information concerning the gene structure and outlines the developmental and spatial regulation of Drosophila melanogaster calmodulin transcripts. The gene contains five exons, including a 49 bp exon in the 5' untranslated region, and spans over 16 kb. Homologues to this small, 5' noncoding exon have not been found in other calmodulin genes. The combined level of the transcripts is developmentally regulated, and the relative amounts of the two transcript size classes (1.65 kb and 1.9 kb) are differentially regulated during development. Primer extension experiments and RNase protection mapping show that both size classes of Drosophila calmodulin transcripts initiate at the same site but undergo alternative termination within the final exon. The spatial distribution of calmodulin transcripts was examined by in situ hybridization to sections of adults and to developmentally staged whole mount embryos. Calmodulin transcripts are evenly distributed early in embryogenesis. In later stages of embryogenesis, higher levels accumulate in the developing nerve cord and other tissues. Elevated levels of calmodulin transcripts are seen quite distinctly in the adult neural tissues and in the photoreceptor region of the compound eye."} {"id": "PMID:1280155", "title": "Localization of delta-crystallin RNA during lens morphogenesis and differentiation in the normal and talpid3 chick embryo.", "content": "Embryonic lens fiber cell differentiation in the chick is marked by the accumulation of delta-crystallin protein. The levels of delta-crystallin RNA are shown here to rise dramatically in the cells of the posterior lens pit prior to their elongation and differentiation as lens fibers. This increase correlates with regional proximity to the underlying optic cup (future retina). This accumulation of delta-crystallin RNA during lens induction operates selectively on the delta 1-crystallin transcripts whereas delta 2-crystallin/argininsosuccinate lyase RNA is detectable at lower levels in all developing ocular tissues throughout this period. The talpid3 mutant forms a flat \"bridge\" of thickened placode-like cells in the head epithelium between the two lens placodes, and this bridge also accumulates delta 1-crystallin RNA, suggesting that the selective increase in delta 1-crystallin RNA levels over those of delta 2-crystallin represents an early event in cellular commitment to lens fiber differentiation in the chick. The significance of the sequence of temporal changes in inductive sources for lens fiber formation is discussed, and we propose that the role of the optic cup is to provide, bound to its extra-cellular material (ECM), a high local concentration of the same growth factors which act as fiber inducers in the older eye.", "contents": "Localization of delta-crystallin RNA during lens morphogenesis and differentiation in the normal and talpid3 chick embryo. Embryonic lens fiber cell differentiation in the chick is marked by the accumulation of delta-crystallin protein. The levels of delta-crystallin RNA are shown here to rise dramatically in the cells of the posterior lens pit prior to their elongation and differentiation as lens fibers. This increase correlates with regional proximity to the underlying optic cup (future retina). This accumulation of delta-crystallin RNA during lens induction operates selectively on the delta 1-crystallin transcripts whereas delta 2-crystallin/argininsosuccinate lyase RNA is detectable at lower levels in all developing ocular tissues throughout this period. The talpid3 mutant forms a flat \"bridge\" of thickened placode-like cells in the head epithelium between the two lens placodes, and this bridge also accumulates delta 1-crystallin RNA, suggesting that the selective increase in delta 1-crystallin RNA levels over those of delta 2-crystallin represents an early event in cellular commitment to lens fiber differentiation in the chick. The significance of the sequence of temporal changes in inductive sources for lens fiber formation is discussed, and we propose that the role of the optic cup is to provide, bound to its extra-cellular material (ECM), a high local concentration of the same growth factors which act as fiber inducers in the older eye."} {"id": "PMID:1280156", "title": "Immunolocalization of acidic and basic fibroblast growth factors during mouse odontogenesis.", "content": "Acidic and basic fibroblast growth factors (aFGF and bFGF), are both known to bind to extracellular matrix components, particularly proteoheparin sulfates, and to regulate in vitro proliferation, differentiation and morphology of cells of neuroectodermal and mesodermal origins. Their patterns of distribution were studied during mouse odontogenesis by means of indirect immunofluorescence and immunoperoxidase histochemistry on frozen fixed sections and after Bouin's fixative and paraffin embedding. Localization of aFGF on frozen fixed sections was observed in the oral epithelium, dental lamina and oral mesenchyme (day-12 of gestation), the stellate reticulum and oral epithelium (day-14), the stratum intermedium and at the basal and apical poles of preameloblasts at bell stage. After birth aFGF epitopes were localized within the predentin-dentin area, the stratum intermedium and at the secretory pole of ameloblasts. There was no staining with anti-aFGF antibodies after Bouin's fixative and paraffin embedding. In contrast, using this protocol, intense stainings were found with anti-bFGF antibodies predominantly within dental and peridental basement membranes and mesenchyme: staining of the dental basement membranes was transient (bud and cap stage) and discontinuous; a preferential concentration of bFGF epitopes in the condensed dental mesenchyme of incisors (cap stage) and the dental papillae mesenchymal cells of molars (bell stage) was observed in the posterior and the cervical part of tooth germs. An intense immunostaining of the stellate reticulum with anti-bFGF antibodies was also found on paraffin sections from bud to bell stage.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Immunolocalization of acidic and basic fibroblast growth factors during mouse odontogenesis. Acidic and basic fibroblast growth factors (aFGF and bFGF), are both known to bind to extracellular matrix components, particularly proteoheparin sulfates, and to regulate in vitro proliferation, differentiation and morphology of cells of neuroectodermal and mesodermal origins. Their patterns of distribution were studied during mouse odontogenesis by means of indirect immunofluorescence and immunoperoxidase histochemistry on frozen fixed sections and after Bouin's fixative and paraffin embedding. Localization of aFGF on frozen fixed sections was observed in the oral epithelium, dental lamina and oral mesenchyme (day-12 of gestation), the stellate reticulum and oral epithelium (day-14), the stratum intermedium and at the basal and apical poles of preameloblasts at bell stage. After birth aFGF epitopes were localized within the predentin-dentin area, the stratum intermedium and at the secretory pole of ameloblasts. There was no staining with anti-aFGF antibodies after Bouin's fixative and paraffin embedding. In contrast, using this protocol, intense stainings were found with anti-bFGF antibodies predominantly within dental and peridental basement membranes and mesenchyme: staining of the dental basement membranes was transient (bud and cap stage) and discontinuous; a preferential concentration of bFGF epitopes in the condensed dental mesenchyme of incisors (cap stage) and the dental papillae mesenchymal cells of molars (bell stage) was observed in the posterior and the cervical part of tooth germs. An intense immunostaining of the stellate reticulum with anti-bFGF antibodies was also found on paraffin sections from bud to bell stage.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280157", "title": "Beta 1-integrins on melanoma clones regulate the interaction with autologous cytolytic T-cell clones.", "content": "Tumor clones isolated from the same subcutaneous metastatic lesion of a melanoma patient were used to investigate the potential role of beta 1-integrins (VLA) in the lysability of neoplastic cells by autologous CD3+, WT31+, CD8+ cytotoxic T-cell clones. Phenotypic analysis of melanoma clones for expression of VLA molecules revealed a subset of clones with high expression of VLA-2, VLA-5, and VLA-6. This subset was also characterized by increased susceptibility to lysis by tumor-specific and nonspecific cytotoxic T-lymphocytes from either TILs or PBLs. Blocking assays with monoclonal antibodies indicated that anti-VLA-2, -5, and -6 antibodies could significantly reduce the lysis of VLA-2+, VLA-5+, and VLA-6+ melanoma clones by either specific and nonspecific CTLs. By contrast, no inhibition was seen on lysis of VLA-2-, VLA-5-, and VLA-6-negative tumor cells. These data indicate that expression of some beta 1-integrins on human melanoma can influence the specific and nonspecific T-cell-mediated recognition of neoplastic cells.", "contents": "Beta 1-integrins on melanoma clones regulate the interaction with autologous cytolytic T-cell clones. Tumor clones isolated from the same subcutaneous metastatic lesion of a melanoma patient were used to investigate the potential role of beta 1-integrins (VLA) in the lysability of neoplastic cells by autologous CD3+, WT31+, CD8+ cytotoxic T-cell clones. Phenotypic analysis of melanoma clones for expression of VLA molecules revealed a subset of clones with high expression of VLA-2, VLA-5, and VLA-6. This subset was also characterized by increased susceptibility to lysis by tumor-specific and nonspecific cytotoxic T-lymphocytes from either TILs or PBLs. Blocking assays with monoclonal antibodies indicated that anti-VLA-2, -5, and -6 antibodies could significantly reduce the lysis of VLA-2+, VLA-5+, and VLA-6+ melanoma clones by either specific and nonspecific CTLs. By contrast, no inhibition was seen on lysis of VLA-2-, VLA-5-, and VLA-6-negative tumor cells. These data indicate that expression of some beta 1-integrins on human melanoma can influence the specific and nonspecific T-cell-mediated recognition of neoplastic cells."} {"id": "PMID:1280158", "title": "Template-directed interference footprinting of cytosine contacts in a protein-DNA complex: potent interference by 5-aza-2'-deoxycytidine.", "content": "In the template-directed interference (TDI) footprinting method (Hayashibara & Verdine, 1990), analogs of the naturally occurring DNA bases are incorporated into DNA enzymatically and assayed for interference of sequence-specific binding by a protein. Here we extend this method to include analysis of contacts of amino acid residues to the major groove surface of cytosine residues (TDI-C footprinting). The base analog 5-aza-2'-deoxycytidine, in which the hydrophobic 5-CH of cytosine is replaced by a hydrophilic aza nitrogen, was incorporated into DNA via the corresponding 5'-triphosphate. The analog was found to base pair with guanine during polymerization, resulting in substitution of 2'-deoxycytidine residues. TDI-C footprints of the lambda repressor-OL1 operator complex revealed apparent contacts to the cytosines at operator positions 7 and 8. Inspection of the high-resolution X-ray crystal structure of the lambda-OL1 complex (Clarke et al., 1992; Beamer & Pabo, 1992) revealed that C8 makes a hydrogen binding contact with the Lys3; C7, on the other hand, makes a previously unnoticed hydrophobic contact with the alkane side chain of Lys3. In only the consensus operator half-site was cytosine interference observed, suggesting that the nonconsensus arm binds DNA very differently if at all. The N-terminal arm represents the archetypal case of a sequence-specific peptide-DNA complex characterized at high resolution; thus, the present studies suggest strategies for design and screening of DNA binding peptides. The finding that 5-aza-2'-deoxycytidine inhibits sequence-specific DNA binding proteins may suggest an alternative rationale for the biological activities of this and related azapyrimidine nucleosides.", "contents": "Template-directed interference footprinting of cytosine contacts in a protein-DNA complex: potent interference by 5-aza-2'-deoxycytidine. In the template-directed interference (TDI) footprinting method (Hayashibara & Verdine, 1990), analogs of the naturally occurring DNA bases are incorporated into DNA enzymatically and assayed for interference of sequence-specific binding by a protein. Here we extend this method to include analysis of contacts of amino acid residues to the major groove surface of cytosine residues (TDI-C footprinting). The base analog 5-aza-2'-deoxycytidine, in which the hydrophobic 5-CH of cytosine is replaced by a hydrophilic aza nitrogen, was incorporated into DNA via the corresponding 5'-triphosphate. The analog was found to base pair with guanine during polymerization, resulting in substitution of 2'-deoxycytidine residues. TDI-C footprints of the lambda repressor-OL1 operator complex revealed apparent contacts to the cytosines at operator positions 7 and 8. Inspection of the high-resolution X-ray crystal structure of the lambda-OL1 complex (Clarke et al., 1992; Beamer & Pabo, 1992) revealed that C8 makes a hydrogen binding contact with the Lys3; C7, on the other hand, makes a previously unnoticed hydrophobic contact with the alkane side chain of Lys3. In only the consensus operator half-site was cytosine interference observed, suggesting that the nonconsensus arm binds DNA very differently if at all. The N-terminal arm represents the archetypal case of a sequence-specific peptide-DNA complex characterized at high resolution; thus, the present studies suggest strategies for design and screening of DNA binding peptides. The finding that 5-aza-2'-deoxycytidine inhibits sequence-specific DNA binding proteins may suggest an alternative rationale for the biological activities of this and related azapyrimidine nucleosides."} {"id": "PMID:1280159", "title": "Orientation of the valine-1 side chain of the gramicidin transmembrane channel and implications for channel functioning. A 2H NMR study.", "content": "The orientation of the valine-1 side chain of gramicidin was determined by solid-state 2H NMR using valine-1-deuterated (d8) gramicidin. The peptide was incorporated into DMPC bilayers that were oriented between glass plates. When the plates were oriented with their normal perpendicular to the magnetic field, four quadrupolar splittings were observed of 106, 68, 9.7, and 2.0 kHz. These resonances were assigned to C alpha D, C beta D, and the deuterons of each of the C gamma D3 methyl groups, respectively. The average orientation of the various C-D bonds was calculated with respect to the helix axis. The angle obtained for the C alpha-D resonance was consistent with a single-stranded beta 6.3-helical model for the backbone but not with double-helical models. The angles of the side chain were then fitted to a model for the right-handed beta 6.3-helix. Rotation of the valine-1 side chain yielded a set of torsion angles that matched the angles as determined from the 2H NMR measurements. The corresponding orientation of the valine-1 side chain (chi 1 = -5 degrees) was found to be quite unusual, but it explains well the importance of a branched side chain at position 1 for channel formation and stability. A van der Waals interaction between valine-1 of one monomer and alanine-5 of the other helps to stabilize the gramicidin dimer.", "contents": "Orientation of the valine-1 side chain of the gramicidin transmembrane channel and implications for channel functioning. A 2H NMR study. The orientation of the valine-1 side chain of gramicidin was determined by solid-state 2H NMR using valine-1-deuterated (d8) gramicidin. The peptide was incorporated into DMPC bilayers that were oriented between glass plates. When the plates were oriented with their normal perpendicular to the magnetic field, four quadrupolar splittings were observed of 106, 68, 9.7, and 2.0 kHz. These resonances were assigned to C alpha D, C beta D, and the deuterons of each of the C gamma D3 methyl groups, respectively. The average orientation of the various C-D bonds was calculated with respect to the helix axis. The angle obtained for the C alpha-D resonance was consistent with a single-stranded beta 6.3-helical model for the backbone but not with double-helical models. The angles of the side chain were then fitted to a model for the right-handed beta 6.3-helix. Rotation of the valine-1 side chain yielded a set of torsion angles that matched the angles as determined from the 2H NMR measurements. The corresponding orientation of the valine-1 side chain (chi 1 = -5 degrees) was found to be quite unusual, but it explains well the importance of a branched side chain at position 1 for channel formation and stability. A van der Waals interaction between valine-1 of one monomer and alanine-5 of the other helps to stabilize the gramicidin dimer."} {"id": "PMID:1280161", "title": "The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides.", "content": "The neurokinin-1 receptor binds neurokinin peptides with the potency order of substance P > substance K > neurokinin B. Elucidating the molecular basis of differential peptide selectivity will require the localization of the binding domain on the receptor. In the present report, mutagenesis and heterologous expression experiments reveal that a segment of the extracellular N-terminal sequence of the neurokinin-1 receptor is required for the high-affinity binding of substance P and related peptide agonists. Substitution of amino acid residues in the N-terminal region of the receptor affects the binding affinity of both intact peptides and a C-terminal substance P \"analog\", but not of a nonpeptide antagonist. Glycosylation of the receptor does not change the peptide binding affinity. In addition, substitution of the valine-97 residue in the rat neurokinin-1 receptor by a glutamate residue increases the binding affinity of neurokinin B but not substance P or substance K, suggesting that the second extracellular segment is involved in peptide selectivity. These results indicate that the extracellular domains of neurokinin-1 receptor play a critical role in peptide binding.", "contents": "The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides. The neurokinin-1 receptor binds neurokinin peptides with the potency order of substance P > substance K > neurokinin B. Elucidating the molecular basis of differential peptide selectivity will require the localization of the binding domain on the receptor. In the present report, mutagenesis and heterologous expression experiments reveal that a segment of the extracellular N-terminal sequence of the neurokinin-1 receptor is required for the high-affinity binding of substance P and related peptide agonists. Substitution of amino acid residues in the N-terminal region of the receptor affects the binding affinity of both intact peptides and a C-terminal substance P \"analog\", but not of a nonpeptide antagonist. Glycosylation of the receptor does not change the peptide binding affinity. In addition, substitution of the valine-97 residue in the rat neurokinin-1 receptor by a glutamate residue increases the binding affinity of neurokinin B but not substance P or substance K, suggesting that the second extracellular segment is involved in peptide selectivity. These results indicate that the extracellular domains of neurokinin-1 receptor play a critical role in peptide binding."} {"id": "PMID:1280162", "title": "Inhibitory effects of pectic substances on activated hyaluronidase and histamine release from mast cells.", "content": "In this paper, we report the effect of pectic substances and D-galacturonic acid, the main constituent of pectic substances, on activated hyaluronidase and histamine release from mast cells. Although D-galacturonic acid itself showed no inhibition, IC50 values of hyaluronidase inhibition were correlated with the D-galacturonic-acid content of pectic substances. It was thought that the polymerization of D-galacturonic acid was necessary for inhibition of activated hyaluronidase. This type of inhibition was suggested to be non-competitive by the Lineweaver-Burk plot. Furthermore, pectic substances, including those purified from Gymnema sylvestre, inhibited histamine release from isolated rat peritoneal mast cells, which had been induced by the antigen. These results suggest that pectic substances may have anti-allergic activities.", "contents": "Inhibitory effects of pectic substances on activated hyaluronidase and histamine release from mast cells. In this paper, we report the effect of pectic substances and D-galacturonic acid, the main constituent of pectic substances, on activated hyaluronidase and histamine release from mast cells. Although D-galacturonic acid itself showed no inhibition, IC50 values of hyaluronidase inhibition were correlated with the D-galacturonic-acid content of pectic substances. It was thought that the polymerization of D-galacturonic acid was necessary for inhibition of activated hyaluronidase. This type of inhibition was suggested to be non-competitive by the Lineweaver-Burk plot. Furthermore, pectic substances, including those purified from Gymnema sylvestre, inhibited histamine release from isolated rat peritoneal mast cells, which had been induced by the antigen. These results suggest that pectic substances may have anti-allergic activities."} {"id": "PMID:1280163", "title": "A lymphocyte-specific protein tyrosine kinase, p56lck, regulates the PMA-induced internalization of CD4.", "content": "p56lck, a member of the src family of non-receptor protein tyrosine kinases (PTKs), is expressed predominantly in T-lymphocytes. Association of p56lck with CD4 and CD8 T-cell receptor (TcR) accessory molecules suggests that p56lck may play a specialized role in antigen-induced T-cell activation. CD4 and CD8 molecules are known to stabilize the interaction between TcR and the major histocompatibility complex during T-cell activation. To examine the role of p56lck in the dynamics of the CD4 molecule, p56lck-expressing transfectant cell clones were prepared by the transfection of an lck-gene plasmid containing an inducible promoter into a CD4+lck- human monocytoid cell line. When these transfectant cells were stimulated with phorbol ester, CD4 internalization on these p56lck-expressing cell lines was selectively and markedly retarded, as compared to p56lck-negative control cell lines. When cell-surface CD4 and intracellular CD4 were selectively precipitated after stimulation, the intracellular CD4 molecules were dissociated from p56lck whereas the surface-retained CD4 molecules were still associated with p56lck. Moreover, the dissociation of p56lck from CD4 appeared to occur prior to the PMA-induced internalization of CD4. These data indicate that p56lck regulates the PMA-induced internalization of CD4 possibly via its association with CD4. Treatment with genistein, a PTK inhibitor, revealed that the PTK activity of p56lck might not be involved in this regulatory effect of p56lck on CD4 internalization.", "contents": "A lymphocyte-specific protein tyrosine kinase, p56lck, regulates the PMA-induced internalization of CD4. p56lck, a member of the src family of non-receptor protein tyrosine kinases (PTKs), is expressed predominantly in T-lymphocytes. Association of p56lck with CD4 and CD8 T-cell receptor (TcR) accessory molecules suggests that p56lck may play a specialized role in antigen-induced T-cell activation. CD4 and CD8 molecules are known to stabilize the interaction between TcR and the major histocompatibility complex during T-cell activation. To examine the role of p56lck in the dynamics of the CD4 molecule, p56lck-expressing transfectant cell clones were prepared by the transfection of an lck-gene plasmid containing an inducible promoter into a CD4+lck- human monocytoid cell line. When these transfectant cells were stimulated with phorbol ester, CD4 internalization on these p56lck-expressing cell lines was selectively and markedly retarded, as compared to p56lck-negative control cell lines. When cell-surface CD4 and intracellular CD4 were selectively precipitated after stimulation, the intracellular CD4 molecules were dissociated from p56lck whereas the surface-retained CD4 molecules were still associated with p56lck. Moreover, the dissociation of p56lck from CD4 appeared to occur prior to the PMA-induced internalization of CD4. These data indicate that p56lck regulates the PMA-induced internalization of CD4 possibly via its association with CD4. Treatment with genistein, a PTK inhibitor, revealed that the PTK activity of p56lck might not be involved in this regulatory effect of p56lck on CD4 internalization."} {"id": "PMID:1280164", "title": "Substrate-specific modulation of Src-mediated phosphorylation of Ras and caseins by sphingosines and other substrate modulators.", "content": "It is important for the understanding of protein kinase action to differentiate between regulation at the enzyme and at the substrate levels. For example, the inhibitors dinitrophenol-tyrosine and tyrphostins act at the enzyme level to inhibit phosphorylation of all substrates by c-Src and v-Src kinases. In contrast, polylysine acts at the substrate level to stimulate Src-mediated phosphorylation of beta-casein but to inhibit phosphorylation of alpha-casein. Here we demonstrate novel enzyme-specific and substrate-specific modulations of Src kinase activity of potential physiological significance. At the enzyme level, we observed that c-Src kinase preferentially phosphorylates alpha-casein, while the v-Src kinase prefers beta-casein. At the substrate level we observed substrate-specific modulation by physiological factors including sphingosine, sphingosine derivatives and the ganglioside GM3. Galactosyl-sphingosine (psychosine) was more effective in stimulating phosphorylation of beta-casein and poly(E1A1Y1) than sphingosine. Glucosyl- and lactosyl-sphingosine were ineffective. Rat was extensively phosphorylated by c-Src in the presence of polylysine, and to a lesser extent in the sphingosine and galactosyl-sphingosine. These unexpected differences point out another potential mechanism for regulation of c-Src and v-Src kinase activities and may help to explain some of the pleotyptic manifestations of protein tyrosine kinase actions.", "contents": "Substrate-specific modulation of Src-mediated phosphorylation of Ras and caseins by sphingosines and other substrate modulators. It is important for the understanding of protein kinase action to differentiate between regulation at the enzyme and at the substrate levels. For example, the inhibitors dinitrophenol-tyrosine and tyrphostins act at the enzyme level to inhibit phosphorylation of all substrates by c-Src and v-Src kinases. In contrast, polylysine acts at the substrate level to stimulate Src-mediated phosphorylation of beta-casein but to inhibit phosphorylation of alpha-casein. Here we demonstrate novel enzyme-specific and substrate-specific modulations of Src kinase activity of potential physiological significance. At the enzyme level, we observed that c-Src kinase preferentially phosphorylates alpha-casein, while the v-Src kinase prefers beta-casein. At the substrate level we observed substrate-specific modulation by physiological factors including sphingosine, sphingosine derivatives and the ganglioside GM3. Galactosyl-sphingosine (psychosine) was more effective in stimulating phosphorylation of beta-casein and poly(E1A1Y1) than sphingosine. Glucosyl- and lactosyl-sphingosine were ineffective. Rat was extensively phosphorylated by c-Src in the presence of polylysine, and to a lesser extent in the sphingosine and galactosyl-sphingosine. These unexpected differences point out another potential mechanism for regulation of c-Src and v-Src kinase activities and may help to explain some of the pleotyptic manifestations of protein tyrosine kinase actions."} {"id": "PMID:1280165", "title": "Resonance Raman studies of Rieske-type proteins.", "content": "Resonance Raman (RR) spectra are reported for the [2Fe-2S] Rieske protein from Thermus thermophilus (TRP) and phthalate dioxygenase from Pseudomonas cepacia (PDO) as a function of pH and excitation wavelength. Depolarization ratio measurements are presented for the RR spectra of spinach ferredoxin (SFD), TRP, and PDO at 74 K. By comparison with previously published RR spectra of SFD, we suggest reasonable assignments for the spectra of TRP and PDO. The spectra of PDO exhibit virtually no pH dependence, while significant changes are observed in TRP spectra upon raising the pH from 7.3 to 10.1. One band near 270 cm-1, which consists of components at 266 cm-1 and 274 cm-1, is attributed to Fe(III)-N(His) stretching motions. We suggest that these two components arise from conformers having a protonated-hydrogen-bonded imidazole (266 cm-1) and deprotonated-hydrogen-bonded imidazolate (274 cm-1) coordinated to the Fe/S cluster and that the relative populations of the two species are pH-dependent; a simple structural model is proposed to account for this behavior in the respiratory-type Rieske proteins. In addition, we have identified RR peaks associated with the bridging and terminal sulfur atoms of the Fe-S-N cluster. The RR excitation profiles of peaks associated with these atoms are indistinguishable from each other in TRP (pH 7.3) and PDO and differ greatly from those of [2Fe-2S] ferrodoxins. The profiles are bimodal with maxima near 490 nm and > approx. 550 nm. By contrast, bands associated with the Fe-N stretch show a somewhat different enhancement profile. Upon reduction, RR peaks assigned to Fe-N vibrations are no longer observed, with the resulting spectrum being remarkably similar to that reported for reduced adrenodoxin. This indicates that only modes associated with Fe-S bonds are observed and supports the idea that the reducing electron resides on the iron atom coordinated to the two histidine residues. Taken as a whole, the data are consistent with an St2FeSb2Fe[N(His)]t2 structure for the Rieske-type cluster.", "contents": "Resonance Raman studies of Rieske-type proteins. Resonance Raman (RR) spectra are reported for the [2Fe-2S] Rieske protein from Thermus thermophilus (TRP) and phthalate dioxygenase from Pseudomonas cepacia (PDO) as a function of pH and excitation wavelength. Depolarization ratio measurements are presented for the RR spectra of spinach ferredoxin (SFD), TRP, and PDO at 74 K. By comparison with previously published RR spectra of SFD, we suggest reasonable assignments for the spectra of TRP and PDO. The spectra of PDO exhibit virtually no pH dependence, while significant changes are observed in TRP spectra upon raising the pH from 7.3 to 10.1. One band near 270 cm-1, which consists of components at 266 cm-1 and 274 cm-1, is attributed to Fe(III)-N(His) stretching motions. We suggest that these two components arise from conformers having a protonated-hydrogen-bonded imidazole (266 cm-1) and deprotonated-hydrogen-bonded imidazolate (274 cm-1) coordinated to the Fe/S cluster and that the relative populations of the two species are pH-dependent; a simple structural model is proposed to account for this behavior in the respiratory-type Rieske proteins. In addition, we have identified RR peaks associated with the bridging and terminal sulfur atoms of the Fe-S-N cluster. The RR excitation profiles of peaks associated with these atoms are indistinguishable from each other in TRP (pH 7.3) and PDO and differ greatly from those of [2Fe-2S] ferrodoxins. The profiles are bimodal with maxima near 490 nm and > approx. 550 nm. By contrast, bands associated with the Fe-N stretch show a somewhat different enhancement profile. Upon reduction, RR peaks assigned to Fe-N vibrations are no longer observed, with the resulting spectrum being remarkably similar to that reported for reduced adrenodoxin. This indicates that only modes associated with Fe-S bonds are observed and supports the idea that the reducing electron resides on the iron atom coordinated to the two histidine residues. Taken as a whole, the data are consistent with an St2FeSb2Fe[N(His)]t2 structure for the Rieske-type cluster."} {"id": "PMID:1280166", "title": "Induction of autoantibodies to human enzymes following viral infection: a biologically relevant hypothesis.", "content": "Macro enzymes, i.e. complexes of normal (iso-)enzymes with an immunoglobulin, may be due to immunological cross-reactions evoked by specific viral antigenic determinants that are homologous to regions in the target enzymes. A search of the National Biomedical Research Foundation protein databank with the amino-acid sequence of human pancreatic amylase revealed a marked homology with a fragment of the yellow fever virus major envelope protein E: i.e. an overall identity of 19.7 per cent and a high degree (40.9 per cent) of conservative amino-acid substitutions over 119 amino acids. At each identical position, the corresponding residue of Taka amylase A was examined by three-dimensional structure analysis, to determine whether the position is likely to be buried or exposed. The existence of a site (epitope) on amylase recognized by an anti-amylase antibody is discussed.", "contents": "Induction of autoantibodies to human enzymes following viral infection: a biologically relevant hypothesis. Macro enzymes, i.e. complexes of normal (iso-)enzymes with an immunoglobulin, may be due to immunological cross-reactions evoked by specific viral antigenic determinants that are homologous to regions in the target enzymes. A search of the National Biomedical Research Foundation protein databank with the amino-acid sequence of human pancreatic amylase revealed a marked homology with a fragment of the yellow fever virus major envelope protein E: i.e. an overall identity of 19.7 per cent and a high degree (40.9 per cent) of conservative amino-acid substitutions over 119 amino acids. At each identical position, the corresponding residue of Taka amylase A was examined by three-dimensional structure analysis, to determine whether the position is likely to be buried or exposed. The existence of a site (epitope) on amylase recognized by an anti-amylase antibody is discussed."} {"id": "PMID:1280169", "title": "Non-nucleoside inhibitors of HIV reverse transcriptase: screening successes--clinical failures.", "content": "A little less than two years ago, the first report describing non-nucleoside inhibitors of HIV reverse transcriptase (RT) led to the high anticipation that a range of new drugs could soon be available for the treatment of AIDS. The intervening period has given rise to several such agents but recent clinical trial data has indicated this optimism to be premature. This short review seeks to trace the brief history of the drug discovery process and to assess whether there are lessons to be learnt from the episode.", "contents": "Non-nucleoside inhibitors of HIV reverse transcriptase: screening successes--clinical failures. A little less than two years ago, the first report describing non-nucleoside inhibitors of HIV reverse transcriptase (RT) led to the high anticipation that a range of new drugs could soon be available for the treatment of AIDS. The intervening period has given rise to several such agents but recent clinical trial data has indicated this optimism to be premature. This short review seeks to trace the brief history of the drug discovery process and to assess whether there are lessons to be learnt from the episode."} {"id": "PMID:1280171", "title": "[Affinity chromatography of mouse and rat alpha-fetoproteins on immobilized diethylstilbestrol].", "content": "Alpha-fetoproteins (AFP) from amniotic fluid of mouse and rat demonstrate high affinity and specificity during their binding with immobilized diethylstilbestrol, which allows to isolate these two proteins by one step using the method of affinity chromatography on Sepharose with immobilized diethylstilbestrol. Meanwhile the yield of mouse AFP was 42%, and rat AFP--75%. The preliminary incubation of the amniotic fluid of rat and mouse with free estradiol results in abrupt fall of AFP outcome, which may testify to the binding of estradiol and diethylstilbestrol by the same receptor sites on AFP molecule.", "contents": "[Affinity chromatography of mouse and rat alpha-fetoproteins on immobilized diethylstilbestrol]. Alpha-fetoproteins (AFP) from amniotic fluid of mouse and rat demonstrate high affinity and specificity during their binding with immobilized diethylstilbestrol, which allows to isolate these two proteins by one step using the method of affinity chromatography on Sepharose with immobilized diethylstilbestrol. Meanwhile the yield of mouse AFP was 42%, and rat AFP--75%. The preliminary incubation of the amniotic fluid of rat and mouse with free estradiol results in abrupt fall of AFP outcome, which may testify to the binding of estradiol and diethylstilbestrol by the same receptor sites on AFP molecule."} {"id": "PMID:1280172", "title": "[Ulcerostatic effect of tris-[2-hydroxyethyl] ammonium salt of iron-containing polyacryl acid and its possible mechanisms].", "content": "The study investigated a stimulating effect of tris-[2-hydroxyethyl] ammonium salt of iron-containing polyacryl acid on proliferative processes in the connective tissue in development of experimental gastric ulcer. The drug was found to exhibit an ulcerostatic effect, to change the levels of collagen, noncollagen proteins, glycosaminoglycan fractions, DNA and RNA.", "contents": "[Ulcerostatic effect of tris-[2-hydroxyethyl] ammonium salt of iron-containing polyacryl acid and its possible mechanisms]. The study investigated a stimulating effect of tris-[2-hydroxyethyl] ammonium salt of iron-containing polyacryl acid on proliferative processes in the connective tissue in development of experimental gastric ulcer. The drug was found to exhibit an ulcerostatic effect, to change the levels of collagen, noncollagen proteins, glycosaminoglycan fractions, DNA and RNA."} {"id": "PMID:1280170", "title": "Synthesis and sequence-specific DNA binding of a topoisomerase inhibitory analog of Hoechst 33258 designed for altered base and sequence recognition.", "content": "The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. Intermolecular nuclear Overhauser effects (NOE) between the ligand and the DNA receptor fragment confirm that the ligand binds in the minor groove of the DNA, interacting with the centrally located 5'-GGCCA segment. In contrast to the steric clash between the benzimidazole rings of the parent Hoechst 33258 molecule and the guanine 2-NH2 groups, which renders it G.C avoiding and thus A.T base pair preferring, the ligand 1 described here overcomes these unfavorable interactions and instead exhibits a marked preference of G.C base pairs. This behavior appears to arise from additional stabilization due to H-bonding with the guanine 2-NH2 groups. Although a ligand-induced distortion at the binding site is qualitatively assessable, the overall B-type conformation of the DNA fragment is retained upon complexation. The structural conclusions drawn from the NOE-NMR evidence were confirmed by molecular mechanics and molecular modeling studies.", "contents": "Synthesis and sequence-specific DNA binding of a topoisomerase inhibitory analog of Hoechst 33258 designed for altered base and sequence recognition. The preparation and DNA binding characteristics of a structural analog of Hoechst 33258 bearing two pyridinic nitrogen atoms are described. The 1H NMR signals of the complex formed between the new ligand 1 and decadeoxyribonucleotide d(CATGGCCATG)2 were assigned by employing one- and two-dimensional NMR techniques. Intermolecular nuclear Overhauser effects (NOE) between the ligand and the DNA receptor fragment confirm that the ligand binds in the minor groove of the DNA, interacting with the centrally located 5'-GGCCA segment. In contrast to the steric clash between the benzimidazole rings of the parent Hoechst 33258 molecule and the guanine 2-NH2 groups, which renders it G.C avoiding and thus A.T base pair preferring, the ligand 1 described here overcomes these unfavorable interactions and instead exhibits a marked preference of G.C base pairs. This behavior appears to arise from additional stabilization due to H-bonding with the guanine 2-NH2 groups. Although a ligand-induced distortion at the binding site is qualitatively assessable, the overall B-type conformation of the DNA fragment is retained upon complexation. The structural conclusions drawn from the NOE-NMR evidence were confirmed by molecular mechanics and molecular modeling studies."} {"id": "PMID:1280173", "title": "[Carbonic anhydrase--marker of cell type in cell culture of the guinea pig vas deferens].", "content": "Polyclonal antibodies (PCAB) to smooth muscle myosin (SMM), monoclonal antibodies (MCAB) to cytokeratin 8 (clon HI, IgGI) and H4 (IgM), as well as PCAB to carbonic anhydrase III were used for identification of the cell types in the vas deferens cell culture of guinea pig. Smooth muscle cells (SMC) are identified by intensive staining of PCAB to SMM. Fibroblast-like cells (FBL) are determined by the presence of the filament finest network, apparently responding to the myosin non-muscular forms, which are present in PCAB to SMM. The epithelial cells are stained by MCAB to cytokeratins. PCAB to carbonic anhydrase III interact with all three cell types. In the majority of SMC the enzyme is detected as solitary stripes, though there are diffuse ones across the whole cytoplasms, the nucleus remains clearly visible. Carbonic anhydrase III in epithelial cells is detected only in nucleoli and along nucleus membrane while in FBL--in nucleoli and cytoplasm as focal granulation. PCAB to carbonic anhydrase III may serve as a universal marker for identification of cell type in the guinea pig vas deferens cell culture.", "contents": "[Carbonic anhydrase--marker of cell type in cell culture of the guinea pig vas deferens]. Polyclonal antibodies (PCAB) to smooth muscle myosin (SMM), monoclonal antibodies (MCAB) to cytokeratin 8 (clon HI, IgGI) and H4 (IgM), as well as PCAB to carbonic anhydrase III were used for identification of the cell types in the vas deferens cell culture of guinea pig. Smooth muscle cells (SMC) are identified by intensive staining of PCAB to SMM. Fibroblast-like cells (FBL) are determined by the presence of the filament finest network, apparently responding to the myosin non-muscular forms, which are present in PCAB to SMM. The epithelial cells are stained by MCAB to cytokeratins. PCAB to carbonic anhydrase III interact with all three cell types. In the majority of SMC the enzyme is detected as solitary stripes, though there are diffuse ones across the whole cytoplasms, the nucleus remains clearly visible. Carbonic anhydrase III in epithelial cells is detected only in nucleoli and along nucleus membrane while in FBL--in nucleoli and cytoplasm as focal granulation. PCAB to carbonic anhydrase III may serve as a universal marker for identification of cell type in the guinea pig vas deferens cell culture."} {"id": "PMID:1280174", "title": "[Ammoniacal silver method in alkaline pH range as a technique for detection of morpho-functional features of nerve tissue elements].", "content": "An alkaline range pH 9.1-12.3 instead of values pH 7.0-7.1 was used to localize lysine-rich and arginine-rich nucleoproteins by ammonia silver (AS) staining method (Black and Ansley, 1966) in brain structures of rabbits and rats. This modification of AS method made it steady to reveal lysine-rich and arginine-rich nucleoproteins and was able to demonstrate the high variability of protein localization in relation to the balance of essential amino acids in the brain structures with different functions. The best results of morphological staining of nerve, glial cells and their fibres were found at pH 10.6--the point of maximal dissociation of lysine--NH2 groups. At the same time the new modification of AS method allows the use of all alkaline range pH 9.1-12.3 for revealing the cells of nervous tissue and to vary the treatment of sections with silver ions.", "contents": "[Ammoniacal silver method in alkaline pH range as a technique for detection of morpho-functional features of nerve tissue elements]. An alkaline range pH 9.1-12.3 instead of values pH 7.0-7.1 was used to localize lysine-rich and arginine-rich nucleoproteins by ammonia silver (AS) staining method (Black and Ansley, 1966) in brain structures of rabbits and rats. This modification of AS method made it steady to reveal lysine-rich and arginine-rich nucleoproteins and was able to demonstrate the high variability of protein localization in relation to the balance of essential amino acids in the brain structures with different functions. The best results of morphological staining of nerve, glial cells and their fibres were found at pH 10.6--the point of maximal dissociation of lysine--NH2 groups. At the same time the new modification of AS method allows the use of all alkaline range pH 9.1-12.3 for revealing the cells of nervous tissue and to vary the treatment of sections with silver ions."} {"id": "PMID:1280175", "title": "[Comparative radioautographic evaluation of RNA synthesis in vivo and in biopsy material].", "content": "The liver, kidney, skin biopsies are able to incorporate actively 3H-uridine, and the maximum rate of RNA synthesis over the hepatocyte nuclei in the peripheral zone of the biopsies corresponds to relevant rates in vivo. Only the skin biopsies were distinguished by total cell labelling. Liver, renal, skin capillary endotheliocytes can serve intertissue marker of the diffusion depth of 3H-uridine.", "contents": "[Comparative radioautographic evaluation of RNA synthesis in vivo and in biopsy material]. The liver, kidney, skin biopsies are able to incorporate actively 3H-uridine, and the maximum rate of RNA synthesis over the hepatocyte nuclei in the peripheral zone of the biopsies corresponds to relevant rates in vivo. Only the skin biopsies were distinguished by total cell labelling. Liver, renal, skin capillary endotheliocytes can serve intertissue marker of the diffusion depth of 3H-uridine."} {"id": "PMID:1280176", "title": "Cancer metastasis--a multistep process.", "content": "Dermatologists are confronted daily with proliferative growths which can reach considerable size, but mean no danger to the patient. Seborrheic keratoses are one example. Other growths, such as basal cell carcinoma, are locally destructive. Normally, however, we do not hesitate to reassure the patient about the benignity of the tumor once excised. The malignancy of squamous cell carcinomas and melanoma, however, is undoubted. Thus, excessive proliferation and even local invasiveness are not sufficient to define malignancy. It is the life-threatening aspect of metastasis that physicians are mostly concerned about.", "contents": "Cancer metastasis--a multistep process. Dermatologists are confronted daily with proliferative growths which can reach considerable size, but mean no danger to the patient. Seborrheic keratoses are one example. Other growths, such as basal cell carcinoma, are locally destructive. Normally, however, we do not hesitate to reassure the patient about the benignity of the tumor once excised. The malignancy of squamous cell carcinomas and melanoma, however, is undoubted. Thus, excessive proliferation and even local invasiveness are not sufficient to define malignancy. It is the life-threatening aspect of metastasis that physicians are mostly concerned about."} {"id": "PMID:1280177", "title": "Palliation of malignant bile duct obstruction with metallic biliary endoprostheses: technique, results, and complications.", "content": "Expandable metallic stents were placed in 34 patients with pathologically proved malignant bile duct obstruction to determine ease of insertion, benefits of a one-stage insertion, and cost-effectiveness relative to conventional plastic stents. Thirty-eight strictures, ranging in length from 1 to 7 cm (mean, 3.2 cm), were present in the 34 patients. Strictures were located in the lower common bile duct (n = 22), middle of the common bile duct (n = 6), and hilar confluence (n = 10). In 13 patients (38%) metallic stents were placed at the time of initial biliary drainage (one-stage procedure), while the remaining patients underwent stent placement within 1-7 days of biliary drainage (two-stage procedure). Biliary obstruction was relieved in 31 of 34 patients (91%). Three patients died within 14 days of stent insertion of unrelated causes, without any change in biliary status. Mean duration of follow-up for all patients was 5.3 months (range, 0.5-14 months). Four episodes of stent occlusion occurred in three patients (12% occlusion rate); each episode was treated successfully. The average length of hospital stay for patients who underwent a one-stage procedure was 13 days (range, 3-33 days) and was 20 days (range, 9-42 days) for patients who underwent a two-stage procedure. The facility of one-step insertion, low occlusion rate, and the many strategies available for treatment of occluded stents make metallic stents an attractive alternative to conventional plastic stents in palliating patients with malignant biliary obstruction.", "contents": "Palliation of malignant bile duct obstruction with metallic biliary endoprostheses: technique, results, and complications. Expandable metallic stents were placed in 34 patients with pathologically proved malignant bile duct obstruction to determine ease of insertion, benefits of a one-stage insertion, and cost-effectiveness relative to conventional plastic stents. Thirty-eight strictures, ranging in length from 1 to 7 cm (mean, 3.2 cm), were present in the 34 patients. Strictures were located in the lower common bile duct (n = 22), middle of the common bile duct (n = 6), and hilar confluence (n = 10). In 13 patients (38%) metallic stents were placed at the time of initial biliary drainage (one-stage procedure), while the remaining patients underwent stent placement within 1-7 days of biliary drainage (two-stage procedure). Biliary obstruction was relieved in 31 of 34 patients (91%). Three patients died within 14 days of stent insertion of unrelated causes, without any change in biliary status. Mean duration of follow-up for all patients was 5.3 months (range, 0.5-14 months). Four episodes of stent occlusion occurred in three patients (12% occlusion rate); each episode was treated successfully. The average length of hospital stay for patients who underwent a one-stage procedure was 13 days (range, 3-33 days) and was 20 days (range, 9-42 days) for patients who underwent a two-stage procedure. The facility of one-step insertion, low occlusion rate, and the many strategies available for treatment of occluded stents make metallic stents an attractive alternative to conventional plastic stents in palliating patients with malignant biliary obstruction."} {"id": "PMID:1280178", "title": "RP 58802B, a long-acting beta 2-adrenoceptor agonist: assessment of antiasthma activity in the guinea-pig in vivo.", "content": "We have examined the protective actions of RP 58802B, a novel beta 2-adrenoceptor agonist, administered by the inhaled and oral routes in the anaesthetized and conscious guinea-pig against bronchospasm induced by histamine or antigen (ovalbumin). We have also examined the effects of RP 58802B on airway reactivity and inflammatory cell infiltration in platelet-activating factor (PAF) (aerosol)-induced bronchial hyperreactivity and on PAF (tracheal instillation)-induced microvascular leakage in the guinea-pig. Nebulized RP 58802B produced a rapid onset and long lasting inhibition of histamine-induced bronchospasm in the anaesthetized guinea-pig (EC50 = 3.2 +/- 0.9 micrograms/ml; duration greater than 90 min). Given orally, RP 58802B (5 mg/kg, 60 min before challenge) produced a greater than three-fold shift to the right of the dose-response curve and depressed the maximum response to histamine by 39 +/- 11%. Increasing the concentration to 25 mg/kg had no futher effect. Similar protection was still seen 4 h after oral dosing. In conscious guinea-pigs, RP 58802B (5 or 25 mg/kg, p.o. 60 min before challenge) significantly attenuated antigen-induced dyspnoea with the time to severe dyspnoea increasing from 170 +/- 32 to 325 +/- 32 s at the higher dose of drug. RP 58802B (10 or 25 mg/kg, p.o. 60 min before exposure to PAF) prevented the development of bronchial hyperreactivity. Although PAF-induced bronchial hyperreactivity was not accompanied by an increase in the number of pulmonary eosinophils, RP 58802B (25 mg/kg p.o.) reduced the numbers of eosinophils recovered by lavage. RP 58802B (10 mg/kg p.o.) significantly inhibited PAF-induced microvascular leakage into guinea-pig lung. These data suggest that RP 58802B, in addition to being a potent and long acting bronchodilator, may have a prophylactic role in preventing bronchial hyperreactivity and in reducing plasma exudation into the lungs.", "contents": "RP 58802B, a long-acting beta 2-adrenoceptor agonist: assessment of antiasthma activity in the guinea-pig in vivo. We have examined the protective actions of RP 58802B, a novel beta 2-adrenoceptor agonist, administered by the inhaled and oral routes in the anaesthetized and conscious guinea-pig against bronchospasm induced by histamine or antigen (ovalbumin). We have also examined the effects of RP 58802B on airway reactivity and inflammatory cell infiltration in platelet-activating factor (PAF) (aerosol)-induced bronchial hyperreactivity and on PAF (tracheal instillation)-induced microvascular leakage in the guinea-pig. Nebulized RP 58802B produced a rapid onset and long lasting inhibition of histamine-induced bronchospasm in the anaesthetized guinea-pig (EC50 = 3.2 +/- 0.9 micrograms/ml; duration greater than 90 min). Given orally, RP 58802B (5 mg/kg, 60 min before challenge) produced a greater than three-fold shift to the right of the dose-response curve and depressed the maximum response to histamine by 39 +/- 11%. Increasing the concentration to 25 mg/kg had no futher effect. Similar protection was still seen 4 h after oral dosing. In conscious guinea-pigs, RP 58802B (5 or 25 mg/kg, p.o. 60 min before challenge) significantly attenuated antigen-induced dyspnoea with the time to severe dyspnoea increasing from 170 +/- 32 to 325 +/- 32 s at the higher dose of drug. RP 58802B (10 or 25 mg/kg, p.o. 60 min before exposure to PAF) prevented the development of bronchial hyperreactivity. Although PAF-induced bronchial hyperreactivity was not accompanied by an increase in the number of pulmonary eosinophils, RP 58802B (25 mg/kg p.o.) reduced the numbers of eosinophils recovered by lavage. RP 58802B (10 mg/kg p.o.) significantly inhibited PAF-induced microvascular leakage into guinea-pig lung. These data suggest that RP 58802B, in addition to being a potent and long acting bronchodilator, may have a prophylactic role in preventing bronchial hyperreactivity and in reducing plasma exudation into the lungs."} {"id": "PMID:1280179", "title": "[Survival of the human immunodeficiency virus (HIV-1) in Triatoma infestans (Klug, 1834)].", "content": "Triatoma infestans is the main domestic vector of Trypanosoma cruzi, the parasitic agent of Chagas' disease in South America. We investigated whether Triatoma infestans could shelter the HIV-1 virus. For this purpose, we measured the survival time of the virus in the alimentary tract. Fifth-instar nymphs of the blood-sucking bug were fed through an ad hoc apparatus with venous blood from asymptomatic HIV-1 seropositive patients. We attempted to evidence the virus by cultivating material from the insect gut (wall and content) on lymphocyte co-culture. Retrovirus activity was demonstrated in the culture supernatant by dosing the p24 antigen and the reverse transcriptase activity. The virus has been found alive in the gut content of Triatoma infestans up to the 7th day after the last infectious meal of the insect.", "contents": "[Survival of the human immunodeficiency virus (HIV-1) in Triatoma infestans (Klug, 1834)]. Triatoma infestans is the main domestic vector of Trypanosoma cruzi, the parasitic agent of Chagas' disease in South America. We investigated whether Triatoma infestans could shelter the HIV-1 virus. For this purpose, we measured the survival time of the virus in the alimentary tract. Fifth-instar nymphs of the blood-sucking bug were fed through an ad hoc apparatus with venous blood from asymptomatic HIV-1 seropositive patients. We attempted to evidence the virus by cultivating material from the insect gut (wall and content) on lymphocyte co-culture. Retrovirus activity was demonstrated in the culture supernatant by dosing the p24 antigen and the reverse transcriptase activity. The virus has been found alive in the gut content of Triatoma infestans up to the 7th day after the last infectious meal of the insect."} {"id": "PMID:1280181", "title": "Effect of charybdotoxin and leiurotoxin I on potassium currents in bullfrog sympathetic ganglion and hippocampal neurons.", "content": "The effects of charybdotoxin and leiurotoxin I were examined on several classes of K+ currents in bullfrog sympathetic ganglion and hippocampal CA1 pyramidal neurons. Highly purified preparations of charybdotoxin selectively blocked a large voltage- and Ca(2+)-dependent K+ current (IC) responsible for action potential repolarization (IC50 = 6 nM) while leiurotoxin I selectively blocked a small Ca(2+)-dependent K+ conductance (IAHP) responsible for the slow afterhyperpolarization following an action potential (IC50 = 7.5 nM) in bullfrog sympathetic ganglion neurons. Neither of the toxins had significant effects on other K+ currents (M-current [IM], A-current [IA] and the delayed rectifier [IK]) present in these cells. Leiurotoxin I at a concentration of 20 nM had no detectable effect on currents in hippocampal CA1 pyramidal neurons. This lack of effect on IAHP in central neurons suggests that the channels underlying slow AHPs in those neurons are pharmacologically distinct from analogous channels in peripheral neurons.", "contents": "Effect of charybdotoxin and leiurotoxin I on potassium currents in bullfrog sympathetic ganglion and hippocampal neurons. The effects of charybdotoxin and leiurotoxin I were examined on several classes of K+ currents in bullfrog sympathetic ganglion and hippocampal CA1 pyramidal neurons. Highly purified preparations of charybdotoxin selectively blocked a large voltage- and Ca(2+)-dependent K+ current (IC) responsible for action potential repolarization (IC50 = 6 nM) while leiurotoxin I selectively blocked a small Ca(2+)-dependent K+ conductance (IAHP) responsible for the slow afterhyperpolarization following an action potential (IC50 = 7.5 nM) in bullfrog sympathetic ganglion neurons. Neither of the toxins had significant effects on other K+ currents (M-current [IM], A-current [IA] and the delayed rectifier [IK]) present in these cells. Leiurotoxin I at a concentration of 20 nM had no detectable effect on currents in hippocampal CA1 pyramidal neurons. This lack of effect on IAHP in central neurons suggests that the channels underlying slow AHPs in those neurons are pharmacologically distinct from analogous channels in peripheral neurons."} {"id": "PMID:1280182", "title": "[10 acute-phase reactive proteins and burn metabolism].", "content": "In order to delineate the relation between acute-phase reaction and burn metabolism, ten serum acute-phase reactive proteins, resting energy expenditure, some hormones and urine nitrogen were assayed in 23 adults with burn of 40%-60% TBSA immediately after the injury to the 10th day postburn. The results were as follows: 1. the levels of Palb, TF, FN and CP were reduced immediately after burn. They were still lower than normal on PBD10; 2. The levels of a-AT, C3c and C4 were decreased slightly, then increased. They were already higher than normal on PBD10; 3. On PBD1, the levels of CRP, HP and a-AG were higher than normal, and then they continued to increase. They were directly proportional to REE and urine nitrogen. It was thought that some serum acute-phase reactive proteins were correlative with metabolism after burn. CPR, a-AG and HP could be used as referential indices to predict change in energy expenditure after burn.", "contents": "[10 acute-phase reactive proteins and burn metabolism]. In order to delineate the relation between acute-phase reaction and burn metabolism, ten serum acute-phase reactive proteins, resting energy expenditure, some hormones and urine nitrogen were assayed in 23 adults with burn of 40%-60% TBSA immediately after the injury to the 10th day postburn. The results were as follows: 1. the levels of Palb, TF, FN and CP were reduced immediately after burn. They were still lower than normal on PBD10; 2. The levels of a-AT, C3c and C4 were decreased slightly, then increased. They were already higher than normal on PBD10; 3. On PBD1, the levels of CRP, HP and a-AG were higher than normal, and then they continued to increase. They were directly proportional to REE and urine nitrogen. It was thought that some serum acute-phase reactive proteins were correlative with metabolism after burn. CPR, a-AG and HP could be used as referential indices to predict change in energy expenditure after burn."} {"id": "PMID:1280183", "title": "Structure of the polysaccharide chains of Pseudomonas pseudomallei lipopolysaccharides.", "content": "The pathogenic bacterium Pseudomonas pseudomallei strain 57576 produces two partially O-acetylated O-antigenic polysaccharides (PS-I and PS-II). Methylation analysis and 1H and 13C NMR spectroscopy, including NOE experiments, showed PS-I to have the structure [formula: see text] and PS-II to have the structure [formula: see text] where 6dmanHep is the unusual higher sugar 6-deoxy-D-manno-heptose. PS-II is produced also by P. pseudomallei strains 100 and 110, and PS-I and O-deacetylated PS-II by strain 97.", "contents": "Structure of the polysaccharide chains of Pseudomonas pseudomallei lipopolysaccharides. The pathogenic bacterium Pseudomonas pseudomallei strain 57576 produces two partially O-acetylated O-antigenic polysaccharides (PS-I and PS-II). Methylation analysis and 1H and 13C NMR spectroscopy, including NOE experiments, showed PS-I to have the structure [formula: see text] and PS-II to have the structure [formula: see text] where 6dmanHep is the unusual higher sugar 6-deoxy-D-manno-heptose. PS-II is produced also by P. pseudomallei strains 100 and 110, and PS-I and O-deacetylated PS-II by strain 97."} {"id": "PMID:1280184", "title": "Purkinje fibre-papillary muscle interaction in the genesis of triggered activity in a guinea pig model.", "content": "Previous studies have attempted to characterise the genesis of triggered activity related to early afterdepolarisations. Little is known about their conduction behaviour. This study was designed to examine the origin and conduction behaviour of triggered activations to throw light on the pathogenesis of torsade de pointes. Electrophysiological interactions related to triggered activations and early afterdepolarisations between papillary muscle and Purkinje fibres were studied in the guinea pig in a single chambered bath. EDTA (5 mM) in Tyrode's solution was used and microelectrodes were placed in both papillary muscle and Purkinje fibres. During early superfusion, marked prolongation of action potential duration and early afterdepolarisations occurred in Purkinje fibres but not in papillary muscle. In addition: (1) with prolongation of action potential duration and early afterdepolarisations in Purkinje fibres, triggered activations arose during phase 2 and were conducted to papillary muscle, where they induced activations; (2) the number of papillary muscle discharges increased with the increase in Purkinje fibre action potential duration in a linear correlation; (3) severing a segment of papillary muscle from Purkinje fibres eliminated these papillary muscle activations; (4) some triggered activations did not conduct to papillary muscle; these had smaller amplitude, slower rate of depolarisation (dV/dt), more positive activation voltage, and similar peak voltages compared to conducted triggered activations; (5) a low plateau resulting from electrotonic interaction was recorded at the Purkinje fibre-papillary muscle junction; this plateau may have facilitated conduction of triggered activations. In this preparation there was a disparity of effect on Purkinje fibre and papillary muscle. Prolongation of action potential duration and repetitive activations due to early afterdepolarisations originated in Purkinje fibres and were conducted to papillary muscle. Purkinje fibre-papillary muscle interactions are of interest in relation to torsade de pointes arrhythmias which are believed to arise from this mechanism.", "contents": "Purkinje fibre-papillary muscle interaction in the genesis of triggered activity in a guinea pig model. Previous studies have attempted to characterise the genesis of triggered activity related to early afterdepolarisations. Little is known about their conduction behaviour. This study was designed to examine the origin and conduction behaviour of triggered activations to throw light on the pathogenesis of torsade de pointes. Electrophysiological interactions related to triggered activations and early afterdepolarisations between papillary muscle and Purkinje fibres were studied in the guinea pig in a single chambered bath. EDTA (5 mM) in Tyrode's solution was used and microelectrodes were placed in both papillary muscle and Purkinje fibres. During early superfusion, marked prolongation of action potential duration and early afterdepolarisations occurred in Purkinje fibres but not in papillary muscle. In addition: (1) with prolongation of action potential duration and early afterdepolarisations in Purkinje fibres, triggered activations arose during phase 2 and were conducted to papillary muscle, where they induced activations; (2) the number of papillary muscle discharges increased with the increase in Purkinje fibre action potential duration in a linear correlation; (3) severing a segment of papillary muscle from Purkinje fibres eliminated these papillary muscle activations; (4) some triggered activations did not conduct to papillary muscle; these had smaller amplitude, slower rate of depolarisation (dV/dt), more positive activation voltage, and similar peak voltages compared to conducted triggered activations; (5) a low plateau resulting from electrotonic interaction was recorded at the Purkinje fibre-papillary muscle junction; this plateau may have facilitated conduction of triggered activations. In this preparation there was a disparity of effect on Purkinje fibre and papillary muscle. Prolongation of action potential duration and repetitive activations due to early afterdepolarisations originated in Purkinje fibres and were conducted to papillary muscle. Purkinje fibre-papillary muscle interactions are of interest in relation to torsade de pointes arrhythmias which are believed to arise from this mechanism."} {"id": "PMID:1280186", "title": "Structure-function subcompartments of the mammalian cell nucleus as revealed by the electron microscopic affinity cytochemistry.", "content": "This electron microscopy review documents the in situ cytochemical localization of important nuclear structures and relates this to the important nuclear functions of RNA transcription and processing. With the help of specific probes (antibodies, nucleic acid probes), a comprehensive picture of nuclear subcompartmentalization is beginning to emerge.", "contents": "Structure-function subcompartments of the mammalian cell nucleus as revealed by the electron microscopic affinity cytochemistry. This electron microscopy review documents the in situ cytochemical localization of important nuclear structures and relates this to the important nuclear functions of RNA transcription and processing. With the help of specific probes (antibodies, nucleic acid probes), a comprehensive picture of nuclear subcompartmentalization is beginning to emerge."} {"id": "PMID:1280187", "title": "Regulation of macromolecular traffic mediated by the nuclear pore complex.", "content": "A sophisticated selective mechanism that regulates nuclear-cytoplasmic traffic has evolved in eukaryotes which circumvents the formidable barrier presented by the nuclear envelope. The sites of RNA and protein exchanges are the nuclear pore complexes (NPCs), 125 MDa supramolecular assemblies inserted into the envelope (see recent reviews by Dingwall, 1991; Goldfarb and Michaud, 1991; Miller et al., 1991; Nigg et al., 1991). In this article, the role NPCs play in regulating intracellular macromolecular traffic will be discussed.", "contents": "Regulation of macromolecular traffic mediated by the nuclear pore complex. A sophisticated selective mechanism that regulates nuclear-cytoplasmic traffic has evolved in eukaryotes which circumvents the formidable barrier presented by the nuclear envelope. The sites of RNA and protein exchanges are the nuclear pore complexes (NPCs), 125 MDa supramolecular assemblies inserted into the envelope (see recent reviews by Dingwall, 1991; Goldfarb and Michaud, 1991; Miller et al., 1991; Nigg et al., 1991). In this article, the role NPCs play in regulating intracellular macromolecular traffic will be discussed."} {"id": "PMID:1280188", "title": "The immune system and gynaecological cancer.", "content": "There have been major advances in our understanding of the cellular and humoral immune mechanisms involved in antitumour activities. The characterization of soluble mediators of the immune response and their synthesis as recombinant proteins has led to an explosion of research activity concerning their role as antitumour agents and also as contributors to the pathogenesis of cancer. It is evident that cytokine production is not restricted to cells of the immune system, and that cytokines are involved in a variety of cell regulatory processes ranging from embryonic development to tissue differentiation. Their production by immune cells may enable interactions between the immune system and other homeostatic systems of the body. The therapeutic role of some cytokines such as the interferons and IL-2 in the routine management of gynaecological cancers needs to be investigated further because of their promise as antitumour agents. The study of cytokine production and cytokine receptor expression by cancers is potentially of great therapeutic value. Identification of cytokines that contribute to tumour progression may paradoxically lead to the treatment of cancers by agents that antagonize their biological effects and to rationalization of future trials of cytokine therapy.", "contents": "The immune system and gynaecological cancer. There have been major advances in our understanding of the cellular and humoral immune mechanisms involved in antitumour activities. The characterization of soluble mediators of the immune response and their synthesis as recombinant proteins has led to an explosion of research activity concerning their role as antitumour agents and also as contributors to the pathogenesis of cancer. It is evident that cytokine production is not restricted to cells of the immune system, and that cytokines are involved in a variety of cell regulatory processes ranging from embryonic development to tissue differentiation. Their production by immune cells may enable interactions between the immune system and other homeostatic systems of the body. The therapeutic role of some cytokines such as the interferons and IL-2 in the routine management of gynaecological cancers needs to be investigated further because of their promise as antitumour agents. The study of cytokine production and cytokine receptor expression by cancers is potentially of great therapeutic value. Identification of cytokines that contribute to tumour progression may paradoxically lead to the treatment of cancers by agents that antagonize their biological effects and to rationalization of future trials of cytokine therapy."} {"id": "PMID:1280189", "title": "Contrast in adenine uptake by chicken and rabbit erythrocytes in vitro.", "content": "1. Relative to rabbit erythrocytes, chicken red blood cells exhibit a much greater capacity to utilize [3H]adenine for nucleotide synthesis in vitro, even at 5 degrees C and in the absence of added inorganic phosphate. 2. This difference is largely due to a higher concentration of phosphoribosylpyrophosphate and greater activity of adenine phosphoribosyltransferase in the avian cells. 3. The capacity of avian erythrocytes for utilization of guanine and hypoxanthine is several fold less than that of adenine. 4. The data are consistent with lower activity for hypoxanthine/guanine phosphoribosyltransferase than for adenine phosphoribosyltransferase in intact chicken erythrocytes. 5. The results indicate that reutilization of adenine by chicken erythrocytes may be physiologically significant.", "contents": "Contrast in adenine uptake by chicken and rabbit erythrocytes in vitro. 1. Relative to rabbit erythrocytes, chicken red blood cells exhibit a much greater capacity to utilize [3H]adenine for nucleotide synthesis in vitro, even at 5 degrees C and in the absence of added inorganic phosphate. 2. This difference is largely due to a higher concentration of phosphoribosylpyrophosphate and greater activity of adenine phosphoribosyltransferase in the avian cells. 3. The capacity of avian erythrocytes for utilization of guanine and hypoxanthine is several fold less than that of adenine. 4. The data are consistent with lower activity for hypoxanthine/guanine phosphoribosyltransferase than for adenine phosphoribosyltransferase in intact chicken erythrocytes. 5. The results indicate that reutilization of adenine by chicken erythrocytes may be physiologically significant."} {"id": "PMID:1280190", "title": "Cardiac arrhythmias during postural drainage and chest percussion of critically ill patients.", "content": "In this study we determine the prevalence and type of arrhythmias that occur during postural drainage and chest percussion (PDP) of critically ill patients, and identify those patients who are most at risk of developing them. We monitored the vital signs and ECGs of 72 ICU patients during their initial PDP treatment. Eight patients (11.1 percent) had development of major arrhythmias, 18 (25 percent) had minor arrhythmias, and 46 (63.9 percent) had none. Increased age (p < 0.0001) and the presence of acute cardiac disorders (p < 0.001) were associated with increased risk of arrhythmias. Individuals experiencing major arrhythmias had a significantly decreased BP and respiratory rate with an increased heart rate during PDP. We conclude that arrhythmias are common during PDP of critically ill patients and recommend that ICU patients be carefully monitored during PDP. When considering PDP for older patients and patients with acute cardiac disease, physicians should carefully weigh the risk of arrhythmias against the benefits of this treatment.", "contents": "Cardiac arrhythmias during postural drainage and chest percussion of critically ill patients. In this study we determine the prevalence and type of arrhythmias that occur during postural drainage and chest percussion (PDP) of critically ill patients, and identify those patients who are most at risk of developing them. We monitored the vital signs and ECGs of 72 ICU patients during their initial PDP treatment. Eight patients (11.1 percent) had development of major arrhythmias, 18 (25 percent) had minor arrhythmias, and 46 (63.9 percent) had none. Increased age (p < 0.0001) and the presence of acute cardiac disorders (p < 0.001) were associated with increased risk of arrhythmias. Individuals experiencing major arrhythmias had a significantly decreased BP and respiratory rate with an increased heart rate during PDP. We conclude that arrhythmias are common during PDP of critically ill patients and recommend that ICU patients be carefully monitored during PDP. When considering PDP for older patients and patients with acute cardiac disease, physicians should carefully weigh the risk of arrhythmias against the benefits of this treatment."} {"id": "PMID:1280191", "title": "Alteration of plasma proteinase-antiproteinase system in type 1 diabetic patients. Influence of sex and relationship with metabolic control.", "content": "The aim of the present study was to investigate whether or not alterations of the plasma proteinase-antiproteinase system were present in type 1 (insulin-dependent) diabetic patients and, if so, whether or not they were related to sex, age at onset and duration of the disease as well as to short- and long-term diabetic control. The plasma concentration of trypsin-like activity and two of the most important plasma serine proteinase inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin, were determined in 95 type 1 diabetic and 67 control subjects. The plasma concentration of alpha 1 antitrypsin was found to be markedly decreased (P < 0.001), whereas plasma alpha 2-macroglobulin and trypsin-like activity were increased in diabetics compared to controls (P = 0.009 and < 0.001, respectively). Sex also influenced the values of both proteinase inhibitors in diabetics, women showing higher values of plasma alpha 1-antitrypsin (P = 0.004) than men. In women, HbA1c was also positively correlated with blood glucose (P < 0.001), daily insulin dosage (P < 0.001), and trypsin-like activity of plasma (P = 0.02). On the contrary, in men, HbA1c appeared to be negatively correlated with plasma alpha 2-macroglobulin (P = 0.02). In addition to sex, age at onset (but not duration) of the disease revealed differences in plasma alpha 1-antitrypsin among diabetics, the lowest mean value of this inhibitor being present in men with age at onset below 15 years, who also showed a significant negative correlation between this inhibitor and HbA1c (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Alteration of plasma proteinase-antiproteinase system in type 1 diabetic patients. Influence of sex and relationship with metabolic control. The aim of the present study was to investigate whether or not alterations of the plasma proteinase-antiproteinase system were present in type 1 (insulin-dependent) diabetic patients and, if so, whether or not they were related to sex, age at onset and duration of the disease as well as to short- and long-term diabetic control. The plasma concentration of trypsin-like activity and two of the most important plasma serine proteinase inhibitors, alpha 1-antitrypsin and alpha 2-macroglobulin, were determined in 95 type 1 diabetic and 67 control subjects. The plasma concentration of alpha 1 antitrypsin was found to be markedly decreased (P < 0.001), whereas plasma alpha 2-macroglobulin and trypsin-like activity were increased in diabetics compared to controls (P = 0.009 and < 0.001, respectively). Sex also influenced the values of both proteinase inhibitors in diabetics, women showing higher values of plasma alpha 1-antitrypsin (P = 0.004) than men. In women, HbA1c was also positively correlated with blood glucose (P < 0.001), daily insulin dosage (P < 0.001), and trypsin-like activity of plasma (P = 0.02). On the contrary, in men, HbA1c appeared to be negatively correlated with plasma alpha 2-macroglobulin (P = 0.02). In addition to sex, age at onset (but not duration) of the disease revealed differences in plasma alpha 1-antitrypsin among diabetics, the lowest mean value of this inhibitor being present in men with age at onset below 15 years, who also showed a significant negative correlation between this inhibitor and HbA1c (P = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280192", "title": "\"Cross-talk\" in recording evoked potentials.", "content": "When two potentials having large amplitude differences are simultaneously recorded, the large amplitude potential contaminates the small amplitude response. The small, early potentials generated by this contamination resemble far-field potentials. Although scalp-recorded SEP was contaminated by waves similar to the peripheral potential, peak latencies and wave form were not identical. Experiments simulating the recording situation verified the presence of \"cross-talk.\" Capacitive coupling would shift peaks and alter the wave forms. Other possible mechanisms for the cross-talk and methods of minimizing it are offered. One should be cautious interpreting the results when potentials of large amplitude differences are simultaneously recorded.", "contents": "\"Cross-talk\" in recording evoked potentials. When two potentials having large amplitude differences are simultaneously recorded, the large amplitude potential contaminates the small amplitude response. The small, early potentials generated by this contamination resemble far-field potentials. Although scalp-recorded SEP was contaminated by waves similar to the peripheral potential, peak latencies and wave form were not identical. Experiments simulating the recording situation verified the presence of \"cross-talk.\" Capacitive coupling would shift peaks and alter the wave forms. Other possible mechanisms for the cross-talk and methods of minimizing it are offered. One should be cautious interpreting the results when potentials of large amplitude differences are simultaneously recorded."} {"id": "PMID:1280193", "title": "Evaluation of reference sites for scalp potentials evoked by painful and non-painful sural nerve stimulation.", "content": "The objective of this study was to evaluate reference sites for recording the middle- and long-latency scalp potentials elicited by painful and non-painful sural nerve stimulation. Somatosensory evoked potentials (SEPs) were recorded from the scalp, the mastoid, the earlobe, the neck, and the wrist. Each site was referenced to the sterno-vertebral (SV) electrode, which is a balanced non-cephalic reference with essentially no ECG contamination. There was little or no activity recorded between the wrist and SV, and the SV was located within a region extending from the rostral neck to the wrist where the potentials were stable over space. Hence, the SV reference is indifferent for the middle- and long-latency potentials evoked by painful and non-painful sural nerve stimulation. There was, however, significant activity recorded from the earlobe and mastoid, sites which are frequently used as references for the SEP. It is important that investigators using these cephalic references to study the middle- and long-latency peaks of the SEP be aware of this activity as it will distort SEPs recorded from single sites and the SEP scalp topography, distortions which could unnecessarily complicate their interpretation.", "contents": "Evaluation of reference sites for scalp potentials evoked by painful and non-painful sural nerve stimulation. The objective of this study was to evaluate reference sites for recording the middle- and long-latency scalp potentials elicited by painful and non-painful sural nerve stimulation. Somatosensory evoked potentials (SEPs) were recorded from the scalp, the mastoid, the earlobe, the neck, and the wrist. Each site was referenced to the sterno-vertebral (SV) electrode, which is a balanced non-cephalic reference with essentially no ECG contamination. There was little or no activity recorded between the wrist and SV, and the SV was located within a region extending from the rostral neck to the wrist where the potentials were stable over space. Hence, the SV reference is indifferent for the middle- and long-latency potentials evoked by painful and non-painful sural nerve stimulation. There was, however, significant activity recorded from the earlobe and mastoid, sites which are frequently used as references for the SEP. It is important that investigators using these cephalic references to study the middle- and long-latency peaks of the SEP be aware of this activity as it will distort SEPs recorded from single sites and the SEP scalp topography, distortions which could unnecessarily complicate their interpretation."} {"id": "PMID:1280194", "title": "P15 in tibial nerve SEPs as an example of the junctional potential.", "content": "Tibial nerve stimulation at the ankle elicited a stationary, dipolar potential P15/N15 over the buttock with a reference electrode at the contralateral greater trochanter (GTc). P15 was distributed in the rostral and contralateral region and N15 in the caudal and ipsilateral region. The derivation from the contralateral iliac crest to the ipsilateral greater trochanter (ICc-GTi) registered a large P15 (= P15-N15) potential which was well free from artifacts. The Cz'-contralateral knee lead, which had been employed in previous studies, registered a smaller P15 of poor quality. Sequential bipolar recording along the course of the sciatic nerve indicated that P15 was generated around the greater sciatic foramen. Comparison with a simulation study suggested that P15 is a junctional potential which is generated when the sciatic nerve enters the bone at the greater sciatic foramen. P15 is expected to be a useful tool to evaluate the proximal segment of the tibial nerve.", "contents": "P15 in tibial nerve SEPs as an example of the junctional potential. Tibial nerve stimulation at the ankle elicited a stationary, dipolar potential P15/N15 over the buttock with a reference electrode at the contralateral greater trochanter (GTc). P15 was distributed in the rostral and contralateral region and N15 in the caudal and ipsilateral region. The derivation from the contralateral iliac crest to the ipsilateral greater trochanter (ICc-GTi) registered a large P15 (= P15-N15) potential which was well free from artifacts. The Cz'-contralateral knee lead, which had been employed in previous studies, registered a smaller P15 of poor quality. Sequential bipolar recording along the course of the sciatic nerve indicated that P15 was generated around the greater sciatic foramen. Comparison with a simulation study suggested that P15 is a junctional potential which is generated when the sciatic nerve enters the bone at the greater sciatic foramen. P15 is expected to be a useful tool to evaluate the proximal segment of the tibial nerve."} {"id": "PMID:1280195", "title": "The influence of interfering input from the peroneal nerve on tibial-nerve somatosensory evoked potential.", "content": "Using a conditioning-test paradigm, we studied the recovery function of tibial nerve somatosensory evoked potentials (SEPs) conditioned by preceding peroneal nerve stimulation. The inter-stimulus intervals (ISIs) ranged from 0 to 400 msec, where 0 msec indicated simultaneous arrival of tibial and peroneal nerve volleys at the L1 spine. The recovery curve was W-shaped, showing two peaks of SEP suppression, maximum at 6 msec ISI (1st phase) and 50-75 ISI msec (2nd phase). In the 1st phase suppression, we found distinct differences in wave forms between 0-2 msec ISI and 4-6 msec ISI. At 0-2 msec ISI, P40-N50-P60 amplitude decreased and latencies shortened, while P31 and N35 were unchanged. At 4-6 msec ISI, all peaks, possibly excluding P31, were markedly depressed. We attribute the former change to an \"occlusive effect\" and the latter to an \"inhibitory effect,\" each mediated via a central synaptic network between the two nerves. The attenuation of the 2nd but not the 1st phase suppression by peroneal nerve block distal to the stimulating electrodes provided evidence that the 2nd phase suppression resulted primarily from interfering afferent signals generated by peroneal nerve peripheral receptors, activated by foot movement.", "contents": "The influence of interfering input from the peroneal nerve on tibial-nerve somatosensory evoked potential. Using a conditioning-test paradigm, we studied the recovery function of tibial nerve somatosensory evoked potentials (SEPs) conditioned by preceding peroneal nerve stimulation. The inter-stimulus intervals (ISIs) ranged from 0 to 400 msec, where 0 msec indicated simultaneous arrival of tibial and peroneal nerve volleys at the L1 spine. The recovery curve was W-shaped, showing two peaks of SEP suppression, maximum at 6 msec ISI (1st phase) and 50-75 ISI msec (2nd phase). In the 1st phase suppression, we found distinct differences in wave forms between 0-2 msec ISI and 4-6 msec ISI. At 0-2 msec ISI, P40-N50-P60 amplitude decreased and latencies shortened, while P31 and N35 were unchanged. At 4-6 msec ISI, all peaks, possibly excluding P31, were markedly depressed. We attribute the former change to an \"occlusive effect\" and the latter to an \"inhibitory effect,\" each mediated via a central synaptic network between the two nerves. The attenuation of the 2nd but not the 1st phase suppression by peroneal nerve block distal to the stimulating electrodes provided evidence that the 2nd phase suppression resulted primarily from interfering afferent signals generated by peroneal nerve peripheral receptors, activated by foot movement."} {"id": "PMID:1280196", "title": "Assessing brain function in post-traumatic coma by means of bit-mapped SEPs, BAEPs, CT, SPET and clinical scores. Prognostic implications.", "content": "Sixty-eight severely head injured comatose patients were studied. Bit-colour-mapped SEPs to median nerve stimulation, BAEPs, CT and SPET regional values and ICP were assessed in relation to clinical information in evaluating cerebral function. All these variables were related to a 1-year outcome. Statistical tests confirmed the higher predictive reliability of both neurophysiological and perfusive (SPET) functional parameters compared to CT structural findings. Generally, SEPs appeared to be more reliable in predicting outcome than BAEPs. Modifications of frontal components could occur independently of post-central ones, being closely related to underlying cerebral lesions. The parameter showing the greatest correlation with outcome in the first recording session was the P25 latency, whereas this prognostic role was mainly assumed by the amplitude value of the frontal N30-P45 complex in a second recording session carried out during the third week following head trauma.", "contents": "Assessing brain function in post-traumatic coma by means of bit-mapped SEPs, BAEPs, CT, SPET and clinical scores. Prognostic implications. Sixty-eight severely head injured comatose patients were studied. Bit-colour-mapped SEPs to median nerve stimulation, BAEPs, CT and SPET regional values and ICP were assessed in relation to clinical information in evaluating cerebral function. All these variables were related to a 1-year outcome. Statistical tests confirmed the higher predictive reliability of both neurophysiological and perfusive (SPET) functional parameters compared to CT structural findings. Generally, SEPs appeared to be more reliable in predicting outcome than BAEPs. Modifications of frontal components could occur independently of post-central ones, being closely related to underlying cerebral lesions. The parameter showing the greatest correlation with outcome in the first recording session was the P25 latency, whereas this prognostic role was mainly assumed by the amplitude value of the frontal N30-P45 complex in a second recording session carried out during the third week following head trauma."} {"id": "PMID:1280197", "title": "Event-related potential (ERP) correlates of performance of intelligence tests.", "content": "Any relationship between measures of cognitive function and brain electrical activity would be of considerable importance in the objective assessment of patients suspected of intellectual impairment. In healthy subjects, we have found a strong correlation between the event-related potentials evoked by a digit probe identification task and scores on intelligence tests (WAIS). Responses from subjects with higher performance on IQ tests are significantly 'more negative' than those from subjects with lower IQ. The characteristics of these IQ-dependent electrophysiological features suggest that they may be related to the subject's ability to focus on a task.", "contents": "Event-related potential (ERP) correlates of performance of intelligence tests. Any relationship between measures of cognitive function and brain electrical activity would be of considerable importance in the objective assessment of patients suspected of intellectual impairment. In healthy subjects, we have found a strong correlation between the event-related potentials evoked by a digit probe identification task and scores on intelligence tests (WAIS). Responses from subjects with higher performance on IQ tests are significantly 'more negative' than those from subjects with lower IQ. The characteristics of these IQ-dependent electrophysiological features suggest that they may be related to the subject's ability to focus on a task."} {"id": "PMID:1280198", "title": "Modulation of event-related potentials (ERPs) by word repetition in a task with inconsistent mapping between repetition and response.", "content": "ERPs were recorded during 5 blocks of a continuous recognition memory task. In each block words were shown twice, separated by an average of 6 intervening items, and the task was to respond discriminatively on the basis of whether each word was appearing in that block for the first (first presentations) or the second (second presentations) time. In blocks 2-5, half of the words had also been shown in the immediately preceding block, and half were new to the experiment. Subjects were slower and less accurate at identifying first presentations of words that had appeared in the preceding block, as compared to first presentations of entirely new words. In the latency ranges of the N400 and late positive components, ERPs to words that had previously been presented were more positive-going than were ERPs to new words. These 'across-block' ERP repetition effects were qualitatively very similar to, and additive with, those evoked by words repeated within a block. These findings suggest that the effects of word repetition on ERPs are not dependent on an invariant mapping between repetition and response and are not a consequence of facilitated decision/response processing for repeated items.", "contents": "Modulation of event-related potentials (ERPs) by word repetition in a task with inconsistent mapping between repetition and response. ERPs were recorded during 5 blocks of a continuous recognition memory task. In each block words were shown twice, separated by an average of 6 intervening items, and the task was to respond discriminatively on the basis of whether each word was appearing in that block for the first (first presentations) or the second (second presentations) time. In blocks 2-5, half of the words had also been shown in the immediately preceding block, and half were new to the experiment. Subjects were slower and less accurate at identifying first presentations of words that had appeared in the preceding block, as compared to first presentations of entirely new words. In the latency ranges of the N400 and late positive components, ERPs to words that had previously been presented were more positive-going than were ERPs to new words. These 'across-block' ERP repetition effects were qualitatively very similar to, and additive with, those evoked by words repeated within a block. These findings suggest that the effects of word repetition on ERPs are not dependent on an invariant mapping between repetition and response and are not a consequence of facilitated decision/response processing for repeated items."} {"id": "PMID:1280199", "title": "Reversed temporal region asymmetries of P300 topography in left- and right-handed schizophrenic subjects.", "content": "The auditory P300 evoked potential was recorded in 36 subjects: left- (LH) and right-handed (RH) schizophrenic males and LH and RH normal controls. LH and RH normals showed no asymmetry in P300 scalp topography. LH and RH schizophrenics, however, showed lateralized asymmetries in temporal scalp regions: left < right P300 voltage asymmetry in RH schizophrenics and left > right P300 voltage asymmetry in LH schizophrenics. These data suggest that the schizophrenic pathology of P300 neural generators is lateralized according to handedness and provide the first evidence that LH and RH schizophrenics can be dissociated based on left-right voltage asymmetries in P300 topography. These findings further emphasize the need for control of handedness in P300 studies of schizophrenia.", "contents": "Reversed temporal region asymmetries of P300 topography in left- and right-handed schizophrenic subjects. The auditory P300 evoked potential was recorded in 36 subjects: left- (LH) and right-handed (RH) schizophrenic males and LH and RH normal controls. LH and RH normals showed no asymmetry in P300 scalp topography. LH and RH schizophrenics, however, showed lateralized asymmetries in temporal scalp regions: left < right P300 voltage asymmetry in RH schizophrenics and left > right P300 voltage asymmetry in LH schizophrenics. These data suggest that the schizophrenic pathology of P300 neural generators is lateralized according to handedness and provide the first evidence that LH and RH schizophrenics can be dissociated based on left-right voltage asymmetries in P300 topography. These findings further emphasize the need for control of handedness in P300 studies of schizophrenia."} {"id": "PMID:1280202", "title": "Anatomy of the pituitary insulin-like growth factor system.", "content": "In situ hybridization was used to map patterns of gene expression for components of the insulin-like growth factor (IGF) system, including IGF-I and -II, IGF-binding proteins 1-5 (IGFBP1-5), the IGF-I receptor, and GH in the rat pituitary. IGF-I mRNA was concentrated in isolated cells scattered throughout the gland with features typical of nonendocrine folliculo-stellate cells. IGF-II mRNA was abundant in neural (NL) and intermediate lobe (IL) capillaries, and low levels were present in endocrine cells of anterior lobe (AL) and IL. IGFBP1 mRNA was not detected in the pituitary. IGFBP2 mRNA was concentrated in epithelial cells lining AL follicles and in astroglial-like cells (pituicytes) of the NL. IGFBP3 mRNA was localized in isolated cells scattered throughout the AL and NL. IGFBP4 mRNA was relatively abundant in NL pituicytes and was diffusely expressed in the AL. IGFBP5 mRNA was equally abundant in NL and AL, and was localized in folliculo-stellate and epithelial cells of the AL and pituicytes and capillaries of the NL. Neither IGF-I nor IGFBP1-5 were detected in the IL. IGF-I receptor mRNA was abundant and homogeneously distributed throughout the AL and IL, compatible with expression by endocrine cells. There was overlap, but no particular correlation, between IGF system gene expression and GH-producing cells, which were clustered in the dorsal-lateral wings of the AL. In summary, IGF system gene expression is bountiful in the rat pituitary, but does not correlate with sites of GH synthesis. IGF-I receptor mRNA, which might have been expected to localize to somatotrophs, appears to be equally abundant in all of the endocrine cells of both AL and IL; the other constituents of the IGF system are localized in connective tissue and support elements that demonstrate no special anatomical relationship to somatotrophs. Finally, there is remarkably abundant gene expression for IGFBP2, -4, and -5 in the NL.", "contents": "Anatomy of the pituitary insulin-like growth factor system. In situ hybridization was used to map patterns of gene expression for components of the insulin-like growth factor (IGF) system, including IGF-I and -II, IGF-binding proteins 1-5 (IGFBP1-5), the IGF-I receptor, and GH in the rat pituitary. IGF-I mRNA was concentrated in isolated cells scattered throughout the gland with features typical of nonendocrine folliculo-stellate cells. IGF-II mRNA was abundant in neural (NL) and intermediate lobe (IL) capillaries, and low levels were present in endocrine cells of anterior lobe (AL) and IL. IGFBP1 mRNA was not detected in the pituitary. IGFBP2 mRNA was concentrated in epithelial cells lining AL follicles and in astroglial-like cells (pituicytes) of the NL. IGFBP3 mRNA was localized in isolated cells scattered throughout the AL and NL. IGFBP4 mRNA was relatively abundant in NL pituicytes and was diffusely expressed in the AL. IGFBP5 mRNA was equally abundant in NL and AL, and was localized in folliculo-stellate and epithelial cells of the AL and pituicytes and capillaries of the NL. Neither IGF-I nor IGFBP1-5 were detected in the IL. IGF-I receptor mRNA was abundant and homogeneously distributed throughout the AL and IL, compatible with expression by endocrine cells. There was overlap, but no particular correlation, between IGF system gene expression and GH-producing cells, which were clustered in the dorsal-lateral wings of the AL. In summary, IGF system gene expression is bountiful in the rat pituitary, but does not correlate with sites of GH synthesis. IGF-I receptor mRNA, which might have been expected to localize to somatotrophs, appears to be equally abundant in all of the endocrine cells of both AL and IL; the other constituents of the IGF system are localized in connective tissue and support elements that demonstrate no special anatomical relationship to somatotrophs. Finally, there is remarkably abundant gene expression for IGFBP2, -4, and -5 in the NL."} {"id": "PMID:1280200", "title": "Evoked magnetic responses of the human auditory cortex to minor pitch changes: localization of the mismatch field.", "content": "The neuromagnetic source localizations of the auditory M100 and the mismatch field (MMF) were studied using a large-array biomagnetometer. Standard tones of 1000 Hz and deviant tones of 1050 Hz were delivered with 90% and 10% probability, respectively. Wave forms of the derived MMF were computed by examining difference wave forms between the responses to the deviants and the responses to the standards preceding (D-P) and following (D-F) the deviants as well as to all remaining standards (D-A). The subset of standards preceding the deviants was used for a more realistic comparison with the set of deviants (having the same number of epochs and a similar signal-to-noise ratio), while the subset of standards following the deviants served to answer the question whether those standards also elicit an MMF. The MMF deflections were compared with each other, with the \"native\" MMF occurring in response to the deviants, and with wave M100. (The MMF as it appears in the unprocessed response to the deviants was termed \"native\" for an easy distinction from the \"derived\" MMF.) Our results demonstrate a distinct MMF deflection, corresponding in latency to the simultaneously recorded fronto-central electrical MMN. Source analysis, using a single moving dipole model, showed the same spatial localization for the native MMF and for the different derived MMFs. The MMF source location turned out to be significantly anterior, medial and inferior relative to the sources of the M100. The present data also demonstrate that a minor frequency deviation may not activate measurably different M100 generators, yet be sufficient to trigger the nearby but spatially distinct mismatch generator.", "contents": "Evoked magnetic responses of the human auditory cortex to minor pitch changes: localization of the mismatch field. The neuromagnetic source localizations of the auditory M100 and the mismatch field (MMF) were studied using a large-array biomagnetometer. Standard tones of 1000 Hz and deviant tones of 1050 Hz were delivered with 90% and 10% probability, respectively. Wave forms of the derived MMF were computed by examining difference wave forms between the responses to the deviants and the responses to the standards preceding (D-P) and following (D-F) the deviants as well as to all remaining standards (D-A). The subset of standards preceding the deviants was used for a more realistic comparison with the set of deviants (having the same number of epochs and a similar signal-to-noise ratio), while the subset of standards following the deviants served to answer the question whether those standards also elicit an MMF. The MMF deflections were compared with each other, with the \"native\" MMF occurring in response to the deviants, and with wave M100. (The MMF as it appears in the unprocessed response to the deviants was termed \"native\" for an easy distinction from the \"derived\" MMF.) Our results demonstrate a distinct MMF deflection, corresponding in latency to the simultaneously recorded fronto-central electrical MMN. Source analysis, using a single moving dipole model, showed the same spatial localization for the native MMF and for the different derived MMFs. The MMF source location turned out to be significantly anterior, medial and inferior relative to the sources of the M100. The present data also demonstrate that a minor frequency deviation may not activate measurably different M100 generators, yet be sufficient to trigger the nearby but spatially distinct mismatch generator."} {"id": "PMID:1280203", "title": "Porcine granulosa cells do not express transforming growth factor-beta 2 (TGF-beta 2) messenger ribonucleic acid: molecular basis for their inability to produce TGF-beta activity comparable to that of rat granulosa cells.", "content": "In contrast to rat granulosa cells (GC), GC of the pig and cow produce very low levels of transforming growth factor-beta (TGF-beta)-like activity in vitro. Because cultured rat GC predominantly express TGF-beta 2 messenger RNA (mRNA) and secrete high levels of the protein, we hypothesized that TGF-beta 2 mRNA expression by porcine GC might be absent or diminished, thus providing a molecular explanation(s) for their relatively low levels of TGF-beta production. We tested this hypothesis by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay analysis. When analyzed by RT-PCR, porcine GC RNA from 1-3 mm follicles did not yield the expected 489 base pair (bp) TGF-beta 2 product but instead generated a smaller than anticipated 240 bp species; porcine testis RNA generated both the 240 and the anticipated 489 bp products. Sequencing these species indicated that the smaller form was not a novel TGF-beta 2 splice variant, and that the 489-bp product was porcine TGF-beta 2. This is the first reported nucleotide sequence for porcine TGF-beta 2; it is 90% and 91% identical to murine and human TGF-beta 2 sequences, respectively. Further RT-PCR analysis of porcine GC RNA resulted in the identification of bp products representing TGF-beta 1 and TGF-beta 3 mRNA. Enzyme-linked immunosorbent assay analysis of porcine GC conditioned medium confirmed the presence of TGF-beta 1 at very low levels. TGF-beta 2 was undetectable. Comparable analysis of GC from the diethylstilbestrol-treated prepubertal rat demonstrated the presence of TGF-beta 1 and TGF-beta 3 mRNA by RT-PCR and very low levels of the corresponding protein products in conditioned culture medium. Collectively, these results suggest that the inability of porcine GC to express TGF-beta 2 mRNA could explain the very low levels of TGF-beta activity secreted by these cells in vitro.", "contents": "Porcine granulosa cells do not express transforming growth factor-beta 2 (TGF-beta 2) messenger ribonucleic acid: molecular basis for their inability to produce TGF-beta activity comparable to that of rat granulosa cells. In contrast to rat granulosa cells (GC), GC of the pig and cow produce very low levels of transforming growth factor-beta (TGF-beta)-like activity in vitro. Because cultured rat GC predominantly express TGF-beta 2 messenger RNA (mRNA) and secrete high levels of the protein, we hypothesized that TGF-beta 2 mRNA expression by porcine GC might be absent or diminished, thus providing a molecular explanation(s) for their relatively low levels of TGF-beta production. We tested this hypothesis by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay analysis. When analyzed by RT-PCR, porcine GC RNA from 1-3 mm follicles did not yield the expected 489 base pair (bp) TGF-beta 2 product but instead generated a smaller than anticipated 240 bp species; porcine testis RNA generated both the 240 and the anticipated 489 bp products. Sequencing these species indicated that the smaller form was not a novel TGF-beta 2 splice variant, and that the 489-bp product was porcine TGF-beta 2. This is the first reported nucleotide sequence for porcine TGF-beta 2; it is 90% and 91% identical to murine and human TGF-beta 2 sequences, respectively. Further RT-PCR analysis of porcine GC RNA resulted in the identification of bp products representing TGF-beta 1 and TGF-beta 3 mRNA. Enzyme-linked immunosorbent assay analysis of porcine GC conditioned medium confirmed the presence of TGF-beta 1 at very low levels. TGF-beta 2 was undetectable. Comparable analysis of GC from the diethylstilbestrol-treated prepubertal rat demonstrated the presence of TGF-beta 1 and TGF-beta 3 mRNA by RT-PCR and very low levels of the corresponding protein products in conditioned culture medium. Collectively, these results suggest that the inability of porcine GC to express TGF-beta 2 mRNA could explain the very low levels of TGF-beta activity secreted by these cells in vitro."} {"id": "PMID:1280201", "title": "Diagnostic role of brain-stem auditory evoked potentials in neurobrucellosis.", "content": "Evoked potential audiometry and brain-stem auditory evoked potentials were evaluated in 15 patients with systemic brucellosis in whom brucella meningitis was suspected clinically. In 8 patients cerebrospinal fluid (CSF) was abnormal with high brucella titre, and evoked potentials were abnormal in all of them. In 7 patients the CSF was normal and evoked potentials were also normal. Brain-stem auditory evoked potential abnormalities were categorised into 4 types: (1) abnormal wave I, (2) abnormal wave V, both irreversible, (3) prolonged I-III interpeak latencies, and (4) prolonged I-V interpeak latencies, both reversible. These findings are of important diagnostic value and correlate well with the clinical features, aetiopathogenesis and final outcome.", "contents": "Diagnostic role of brain-stem auditory evoked potentials in neurobrucellosis. Evoked potential audiometry and brain-stem auditory evoked potentials were evaluated in 15 patients with systemic brucellosis in whom brucella meningitis was suspected clinically. In 8 patients cerebrospinal fluid (CSF) was abnormal with high brucella titre, and evoked potentials were abnormal in all of them. In 7 patients the CSF was normal and evoked potentials were also normal. Brain-stem auditory evoked potential abnormalities were categorised into 4 types: (1) abnormal wave I, (2) abnormal wave V, both irreversible, (3) prolonged I-III interpeak latencies, and (4) prolonged I-V interpeak latencies, both reversible. These findings are of important diagnostic value and correlate well with the clinical features, aetiopathogenesis and final outcome."} {"id": "PMID:1280204", "title": "Mechanisms of Sertoli cell insulin-like growth factor (IGF)-binding protein-3 regulation by IGF-I and adenosine 3',5'-monophosphate.", "content": "FSH, which stimulates cAMP in the Sertoli cell, markedly lowers the concentration of insulin-like growth factor-binding protein-3 (IGFBP-3) in Sertoli cell-conditioned medium; in contrast, insulin-like growth factor-I (IGF-I) increases BP-3 expression. In this study, the mechanisms controlling the contrasting effects of cAMP and IGF-I were investigated. The abundance of BP-3 mRNA was dramatically lowered by (Bu)2cAMP, but was unaffected by IGF-I. Analyzed by ligand blot of conditioned medium, coincubation of (Bu)2cAMP and IGF-I largely eliminated the increase observed with IGF-I alone. Based on the following evidence, the effect of IGF-I appeared to be solely related to the capacity of IGF-I to interact directly with BP-3. 1) Insulin at micromolar concentrations failed to increase BP-3 abundance despite documentation by affinity cross-linking that insulin displaced [125I]IGF-I from the IGF-I receptor. 2) A synthetic IGF-I analog, [Leu24,1-62]IGF-I, which has reduced binding affinity for rat IGF-I receptor but displays high affinity for rat Sertoli cell-conditioned medium BPs, increased BP-3 abundance. 3) A synthetic IGF-I analog, B-chain mutant, which has reduced affinity for rat Sertoli cell BPs but displays normal affinity for the rat IGF-I receptor, failed to increase BP-3 abundance. 4) Human recombinant glycosylated [125I]BP-3 when added to cultured Sertoli cells was preserved in the medium when IGF-I or analogs with BP-3 affinity were present. 5) IGF-I, in dose-responsive manner, both retarded the disappearance from the medium of exogenously added human recombinant nonglycosylated BP-3 and decreased the amount of membrane-associated BP-3. These results indicate that whereas cAMP lowers BP-3 abundance in medium, most likely by markedly decreasing synthesis, IGF-I increases BP-3 accumulation by retarding its clearance by the Sertoli cell.", "contents": "Mechanisms of Sertoli cell insulin-like growth factor (IGF)-binding protein-3 regulation by IGF-I and adenosine 3',5'-monophosphate. FSH, which stimulates cAMP in the Sertoli cell, markedly lowers the concentration of insulin-like growth factor-binding protein-3 (IGFBP-3) in Sertoli cell-conditioned medium; in contrast, insulin-like growth factor-I (IGF-I) increases BP-3 expression. In this study, the mechanisms controlling the contrasting effects of cAMP and IGF-I were investigated. The abundance of BP-3 mRNA was dramatically lowered by (Bu)2cAMP, but was unaffected by IGF-I. Analyzed by ligand blot of conditioned medium, coincubation of (Bu)2cAMP and IGF-I largely eliminated the increase observed with IGF-I alone. Based on the following evidence, the effect of IGF-I appeared to be solely related to the capacity of IGF-I to interact directly with BP-3. 1) Insulin at micromolar concentrations failed to increase BP-3 abundance despite documentation by affinity cross-linking that insulin displaced [125I]IGF-I from the IGF-I receptor. 2) A synthetic IGF-I analog, [Leu24,1-62]IGF-I, which has reduced binding affinity for rat IGF-I receptor but displays high affinity for rat Sertoli cell-conditioned medium BPs, increased BP-3 abundance. 3) A synthetic IGF-I analog, B-chain mutant, which has reduced affinity for rat Sertoli cell BPs but displays normal affinity for the rat IGF-I receptor, failed to increase BP-3 abundance. 4) Human recombinant glycosylated [125I]BP-3 when added to cultured Sertoli cells was preserved in the medium when IGF-I or analogs with BP-3 affinity were present. 5) IGF-I, in dose-responsive manner, both retarded the disappearance from the medium of exogenously added human recombinant nonglycosylated BP-3 and decreased the amount of membrane-associated BP-3. These results indicate that whereas cAMP lowers BP-3 abundance in medium, most likely by markedly decreasing synthesis, IGF-I increases BP-3 accumulation by retarding its clearance by the Sertoli cell."} {"id": "PMID:1280205", "title": "Phorbol esters differentially regulate the expression of insulin-like growth factor-binding proteins in endometrial carcinoma cells.", "content": "We have examined the effects of protein kinase-C (PKC) activation on expression of the six known insulin-like growth factor-binding proteins (IGFBPs) by human endometrial carcinoma cells. Each of six known IGFBPs was expressed in one or more of the three cell lines examined. The addition of 10(-7) M 4 beta-phorbol 12-myristate 13-acetate (PMA) to HEC-50 and HEC-1B cells resulted in changes in cell morphology, growth inhibition, activation of PKC, and an increase in expression of IGFBP-1. PMA had no effect on these parameters in the Ishikawa cell line, which did not express IGFBP-1. In HEC-50 cells, the effect of PMA was blocked by the concomitant addition of the PKC inhibitor staurosporin and the simultaneous addition of cycloheximide. PMA also resulted in an increase in IGFBP-3 in HEC-50 cells and an increase in IGFBP-6 expression in HEC-1B cells. In contrast, IGFBP-3 expression was down-regulated by PMA in HEC-1B and Ishikawa cells. The abundance of IGFBP-2 and IGFBP-5 mRNAs was also reduced in HEC-1B and Ishikawa cells, respectively. IGFBP-4 was expressed only in HEC-50 cells and was not affected by PMA treatment. These data establish a role for the PKC pathway in regulation of expression of IGFBP-1, -2, -3, and -5 in endometrial adenocarcinoma cells and illustrate the complexity of cell type-specific expression of the IGFBPs.", "contents": "Phorbol esters differentially regulate the expression of insulin-like growth factor-binding proteins in endometrial carcinoma cells. We have examined the effects of protein kinase-C (PKC) activation on expression of the six known insulin-like growth factor-binding proteins (IGFBPs) by human endometrial carcinoma cells. Each of six known IGFBPs was expressed in one or more of the three cell lines examined. The addition of 10(-7) M 4 beta-phorbol 12-myristate 13-acetate (PMA) to HEC-50 and HEC-1B cells resulted in changes in cell morphology, growth inhibition, activation of PKC, and an increase in expression of IGFBP-1. PMA had no effect on these parameters in the Ishikawa cell line, which did not express IGFBP-1. In HEC-50 cells, the effect of PMA was blocked by the concomitant addition of the PKC inhibitor staurosporin and the simultaneous addition of cycloheximide. PMA also resulted in an increase in IGFBP-3 in HEC-50 cells and an increase in IGFBP-6 expression in HEC-1B cells. In contrast, IGFBP-3 expression was down-regulated by PMA in HEC-1B and Ishikawa cells. The abundance of IGFBP-2 and IGFBP-5 mRNAs was also reduced in HEC-1B and Ishikawa cells, respectively. IGFBP-4 was expressed only in HEC-50 cells and was not affected by PMA treatment. These data establish a role for the PKC pathway in regulation of expression of IGFBP-1, -2, -3, and -5 in endometrial adenocarcinoma cells and illustrate the complexity of cell type-specific expression of the IGFBPs."} {"id": "PMID:1280206", "title": "Local synthesis and developmental regulation of avian vitreal insulin-like growth factor-binding proteins: a model for independent regulation in extravascular and vascular compartments.", "content": "The expression and regulation of insulin-like growth factor-binding proteins (IGFBPs) in developing avian vitreous humor and serum were compared. Vitreal IGF-I-binding activity was highest on embryonic day 6 [E-6; bound/free ratio (B/F), 0.22 +/- 0.019/50 microliters), decreased 10-fold between E-6 and E-19, and then remained stable through the remainder of embryonic development. In contrast, serum IGF-I binding increased 2-fold over this period, from a B/F of 0.380 +/- 0.056 (E-6) to a B/F of 0.89 +/- 0.18 (E-19). After hatching, serum IGF-I-binding activity continued to increase through posthatching week 12, while vitreal IGF-I binding increased only slightly and then remained constant. Although IGF-II binding in the vitreous humor and serum is 2- to 3-fold higher than that of IGF-I, the same pattern of developmental regulation was observed as with IGF-I. Western ligand blots revealed a vitreal 24-kilodalton (kDa) IGFBP that was absent from both embryonic and adult sera. Likewise, posthatching serum was found to contain a 70-kDa IGFBP absent in vitreous humor. Deglycosylation of vitreal and serum IGFBPs followed by Western ligand blotting revealed unique glycosylation patterns for vitreal and serum IGFBPs. One of the IGFBPs that is differentially glycosylated in vitreous and serum is a 33-kDa IGFBP that is precipitated with human IGFBP-2 antiserum. Northern blot analysis revealed the presence of IGFBP-2 mRNA in several embryonic ocular tissues as well as liver. The observations that vitreal and serum IGFBP levels are independently regulated during development and that IGFBPs from these two compartments have different molecular weights and glycosylation patterns suggest that the vitreal IGFBPs are not derived from serum. The presence of IGFBP-2 mRNA in ocular tissue surrounding the vitreal chamber supports the view that certain vitreal IGFBPs may be synthesized locally.", "contents": "Local synthesis and developmental regulation of avian vitreal insulin-like growth factor-binding proteins: a model for independent regulation in extravascular and vascular compartments. The expression and regulation of insulin-like growth factor-binding proteins (IGFBPs) in developing avian vitreous humor and serum were compared. Vitreal IGF-I-binding activity was highest on embryonic day 6 [E-6; bound/free ratio (B/F), 0.22 +/- 0.019/50 microliters), decreased 10-fold between E-6 and E-19, and then remained stable through the remainder of embryonic development. In contrast, serum IGF-I binding increased 2-fold over this period, from a B/F of 0.380 +/- 0.056 (E-6) to a B/F of 0.89 +/- 0.18 (E-19). After hatching, serum IGF-I-binding activity continued to increase through posthatching week 12, while vitreal IGF-I binding increased only slightly and then remained constant. Although IGF-II binding in the vitreous humor and serum is 2- to 3-fold higher than that of IGF-I, the same pattern of developmental regulation was observed as with IGF-I. Western ligand blots revealed a vitreal 24-kilodalton (kDa) IGFBP that was absent from both embryonic and adult sera. Likewise, posthatching serum was found to contain a 70-kDa IGFBP absent in vitreous humor. Deglycosylation of vitreal and serum IGFBPs followed by Western ligand blotting revealed unique glycosylation patterns for vitreal and serum IGFBPs. One of the IGFBPs that is differentially glycosylated in vitreous and serum is a 33-kDa IGFBP that is precipitated with human IGFBP-2 antiserum. Northern blot analysis revealed the presence of IGFBP-2 mRNA in several embryonic ocular tissues as well as liver. The observations that vitreal and serum IGFBP levels are independently regulated during development and that IGFBPs from these two compartments have different molecular weights and glycosylation patterns suggest that the vitreal IGFBPs are not derived from serum. The presence of IGFBP-2 mRNA in ocular tissue surrounding the vitreal chamber supports the view that certain vitreal IGFBPs may be synthesized locally."} {"id": "PMID:1280207", "title": "A chimeric analog of human and salmon calcitonin eliminates antigenicity and reduces gastrointestinal disturbances.", "content": "The minimum region in salmon calcitonin (sCT) which induces antigenicity and gastrointestinal disturbances has been identified by examining the cross-reactivity of several sCT fragments and CT analogs with antisera from sCT-treated patients, and by examining inhibition of gastrointestinal motility of these sCT fragments and CT analogs in conscious dogs. Sixteen residues at the N-terminus of sCT comprised the minimum fragment capable of inducing both activities. Human CT (hCT) showed no antigenicity and a four-order weaker inhibition of gastrointestinal motility than sCT. Based on these data, we synthesized the human and salmon chimeric CT, ACT-15, in which the 16 N-terminal residues were those of hCT and the 16 C-terminal residues were those of sCT. ACT-15 had no cross-reactivity with the antisera and had almost the same weak gastrointestinal inhibition effect as hCT in dog and rat models. Nevertheless, it retained a hypocalcemic activity and an analgesic activity comparable to sCT. These results suggest that the amino acid residues in the N-terminal half of CT are responsible for the formation of antibodies and the induction of gastrointestinal disturbances, but may not influence calcium metabolism or analgesia. Clinical studies of ACT-15 will be needed to confirm this hypothesis.", "contents": "A chimeric analog of human and salmon calcitonin eliminates antigenicity and reduces gastrointestinal disturbances. The minimum region in salmon calcitonin (sCT) which induces antigenicity and gastrointestinal disturbances has been identified by examining the cross-reactivity of several sCT fragments and CT analogs with antisera from sCT-treated patients, and by examining inhibition of gastrointestinal motility of these sCT fragments and CT analogs in conscious dogs. Sixteen residues at the N-terminus of sCT comprised the minimum fragment capable of inducing both activities. Human CT (hCT) showed no antigenicity and a four-order weaker inhibition of gastrointestinal motility than sCT. Based on these data, we synthesized the human and salmon chimeric CT, ACT-15, in which the 16 N-terminal residues were those of hCT and the 16 C-terminal residues were those of sCT. ACT-15 had no cross-reactivity with the antisera and had almost the same weak gastrointestinal inhibition effect as hCT in dog and rat models. Nevertheless, it retained a hypocalcemic activity and an analgesic activity comparable to sCT. These results suggest that the amino acid residues in the N-terminal half of CT are responsible for the formation of antibodies and the induction of gastrointestinal disturbances, but may not influence calcium metabolism or analgesia. Clinical studies of ACT-15 will be needed to confirm this hypothesis."} {"id": "PMID:1280208", "title": "Dopaminergic regulation of the GT1 gonadotropin-releasing hormone (GnRH) neuronal cell lines: stimulation of GnRH release via D1-receptors positively coupled to adenylate cyclase.", "content": "The release of GnRH evoked by dopamine (DA) was studied in the GT1 GnRH neuronal cell lines. Superfusion of GT1-1 cells with DA or the D1-dopaminergic agonist SKF 38393, but not with the D2-dopaminergic agonist bromocriptine, increased 2-fold the amplitude of the spontaneous GnRH pulses. Treatment with DA for 30 min also stimulated GnRH release from static cultures of GT1-7 cells. This effect was mimicked by the selective D1-dopaminergic agonist SKF 38393 and blocked by the D1-dopaminergic antagonist SCH 23390. However, the D2-dopaminergic agonist bromocriptine had no effect, and the stimulation of GnRH release by DA was not blocked by the D2-dopaminergic antagonist spiroperidol. In parallel to the stimulation of GnRH release, DA also rapidly increased (first observed at 120 sec) in a dose-dependent fashion, the intracellular concentration of cAMP in isobutylmethylxanthine-pretreated GT1-7 cells. The pharmacological profile of the increase in cAMP was identical to that for GnRH release. The cAMP responses to DA and norepinephrine were lost after long term treatment with SKF 38393, i.e. heterologous desensitization. GT1 cells also express the mRNA for the dopamine- and cAMP-regulated phospho-protein (mol wt, 32,000; DARPP-32) only seen in cells expressing DA D1-receptors. These results demonstrate a direct stimulatory effect of DA on GnRH release via DA D1-receptors positively coupled to adenylate cyclase in GnRH neuronal cell lines.", "contents": "Dopaminergic regulation of the GT1 gonadotropin-releasing hormone (GnRH) neuronal cell lines: stimulation of GnRH release via D1-receptors positively coupled to adenylate cyclase. The release of GnRH evoked by dopamine (DA) was studied in the GT1 GnRH neuronal cell lines. Superfusion of GT1-1 cells with DA or the D1-dopaminergic agonist SKF 38393, but not with the D2-dopaminergic agonist bromocriptine, increased 2-fold the amplitude of the spontaneous GnRH pulses. Treatment with DA for 30 min also stimulated GnRH release from static cultures of GT1-7 cells. This effect was mimicked by the selective D1-dopaminergic agonist SKF 38393 and blocked by the D1-dopaminergic antagonist SCH 23390. However, the D2-dopaminergic agonist bromocriptine had no effect, and the stimulation of GnRH release by DA was not blocked by the D2-dopaminergic antagonist spiroperidol. In parallel to the stimulation of GnRH release, DA also rapidly increased (first observed at 120 sec) in a dose-dependent fashion, the intracellular concentration of cAMP in isobutylmethylxanthine-pretreated GT1-7 cells. The pharmacological profile of the increase in cAMP was identical to that for GnRH release. The cAMP responses to DA and norepinephrine were lost after long term treatment with SKF 38393, i.e. heterologous desensitization. GT1 cells also express the mRNA for the dopamine- and cAMP-regulated phospho-protein (mol wt, 32,000; DARPP-32) only seen in cells expressing DA D1-receptors. These results demonstrate a direct stimulatory effect of DA on GnRH release via DA D1-receptors positively coupled to adenylate cyclase in GnRH neuronal cell lines."} {"id": "PMID:1280209", "title": "Reduction and reoxidation of equine gonadotropin alpha-subunits.", "content": "Ovine (o) and equine (e) LH alpha-subunits were reduced and reoxidized using conditions known to be effective for bovine and human alpha-subunits. The major product of oLH alpha refolding was alpha-subunit monomer. In contrast, eLH alpha formed a 121,000 mol wt aggregate. Monomeric eLH alpha was recovered, but in greatly reduced yield. To test the effects of carbohydrate variation on the aggregation of equine alpha-subunits, all of the equine gonadotropin alpha-subunits (eFSH alpha, eCG alpha, eLH alpha, and free alpha-subunit) were reduced and reoxidized. In each case, the major product was the 121,000 mol wt aggregate accompanied by monomeric equine alpha. Removal of carbohydrate by trifluoromethane sulfonic acid hydrolysis accentuated the tendency to aggregation during reoxidation. Most reduced-reoxidized deglycosylated eLH alpha did not enter a 12% sodium dodecyl sulfate-polyacrylamide gel. The highest LH receptor-binding activities were found in the alpha-subunit preparations, eLH alpha itself and pituitary free alpha-subunit. Operationally, the latter was separated from eLH in the last step of the eLH purification procedure; thus, LH contamination in this preparation is likely. Reduction and reoxidation reduced the LH receptor-binding activity of these two preparations to the level of LH activity observed in the eFSH alpha and eCG alpha preparations. We concluded that the majority of the LH receptor-binding activity observed in equine alpha-subunit preparations was due to contamination with eLH. We also obtained preliminary evidence that the amino-terminal and carboxy-terminal fragments of proteolytically \"nicked\" equine alpha-subunits refolded properly to form alpha monomer.", "contents": "Reduction and reoxidation of equine gonadotropin alpha-subunits. Ovine (o) and equine (e) LH alpha-subunits were reduced and reoxidized using conditions known to be effective for bovine and human alpha-subunits. The major product of oLH alpha refolding was alpha-subunit monomer. In contrast, eLH alpha formed a 121,000 mol wt aggregate. Monomeric eLH alpha was recovered, but in greatly reduced yield. To test the effects of carbohydrate variation on the aggregation of equine alpha-subunits, all of the equine gonadotropin alpha-subunits (eFSH alpha, eCG alpha, eLH alpha, and free alpha-subunit) were reduced and reoxidized. In each case, the major product was the 121,000 mol wt aggregate accompanied by monomeric equine alpha. Removal of carbohydrate by trifluoromethane sulfonic acid hydrolysis accentuated the tendency to aggregation during reoxidation. Most reduced-reoxidized deglycosylated eLH alpha did not enter a 12% sodium dodecyl sulfate-polyacrylamide gel. The highest LH receptor-binding activities were found in the alpha-subunit preparations, eLH alpha itself and pituitary free alpha-subunit. Operationally, the latter was separated from eLH in the last step of the eLH purification procedure; thus, LH contamination in this preparation is likely. Reduction and reoxidation reduced the LH receptor-binding activity of these two preparations to the level of LH activity observed in the eFSH alpha and eCG alpha preparations. We concluded that the majority of the LH receptor-binding activity observed in equine alpha-subunit preparations was due to contamination with eLH. We also obtained preliminary evidence that the amino-terminal and carboxy-terminal fragments of proteolytically \"nicked\" equine alpha-subunits refolded properly to form alpha monomer."} {"id": "PMID:1280210", "title": "Enhanced effectiveness of pulsatile 3',5'-cyclic adenosine monophosphate in stimulating prolactin and alpha-subunit gene expression.", "content": "cAMP is involved in the regulation of secretory activity in lactotrope, thyrotrope, and gonadotrope cells. The present study examined whether pulsatile or intermittent changes in cAMP are more effective than a continuous stimulation in increasing pituitary hormone gene expression. Pituitaries from adult female rats were dissociated, plated for 48 h (7-8 x 10(6) cells per well) to allow attachment to Matrigel-coated plastic coverslips, then inserted into perifusion chambers (five to eight chambers per group). After 24 h of treatment, the cells were recovered, RNA extracted, and messenger RNAs (mRNAs) determined by dot blot hybridization. Perfused cells were exposed to either hourly pulses of monobutyryl cAMP (Bt cAMP, 0.01, 0.1, or 1 mM; 1 mM butyrate pulses to controls), or continuously to forskolin (10 microM). Bt cAMP pulses increased both PRL and alpha-subunit mRNAs, maximal after the 0.1 mM dose for PRL (51% increase vs. butyrate controls) and after the 1 mM dose for alpha (60% increase). However, forskolin was ineffective in increasing PRL or alpha mRNA concentrations. TSH, LH, and FSH beta-subunit mRNAs were not altered by Bt cAMP pulses or forskolin. To confirm the different effects of pulsatile vs. continuous cAMP on PRL and alpha-subunit mRNAs, the response to pulsatile 8-bromo cAMP (1 mM) or Bt cAMP (0.5 mM) was compared to continuous Bt cAMP (0.5 mM). PRL and alpha-subunit mRNAs were increased by both cAMP analogs given in a pulsatile manner but not by continuous Bt cAMP. PRL and LH secretory responses (determined in perifusate samples after 2 h and 22 h of treatment) revealed that both PRL and LH release was increased by cAMP stimulation, given either in a pulsatile or continuous manner. These results show that PRL and alpha-subunit gene expression were sensitive to changes in cAMP stimulation, whereas that of TSH, LH, and FSH beta were unaltered. Only intermittent cAMP stimuli were effective in increasing PRL and alpha mRNAs. These data suggest that pulsatile fluctuations in intracellular cAMP may be essential for maximal expression of the PRL and alpha genes. Thus, intermittent changes in intracellular second messengers may be a necessary part of the pathway involved in the transduction of signals from the plasma membrane to the nucleus.", "contents": "Enhanced effectiveness of pulsatile 3',5'-cyclic adenosine monophosphate in stimulating prolactin and alpha-subunit gene expression. cAMP is involved in the regulation of secretory activity in lactotrope, thyrotrope, and gonadotrope cells. The present study examined whether pulsatile or intermittent changes in cAMP are more effective than a continuous stimulation in increasing pituitary hormone gene expression. Pituitaries from adult female rats were dissociated, plated for 48 h (7-8 x 10(6) cells per well) to allow attachment to Matrigel-coated plastic coverslips, then inserted into perifusion chambers (five to eight chambers per group). After 24 h of treatment, the cells were recovered, RNA extracted, and messenger RNAs (mRNAs) determined by dot blot hybridization. Perfused cells were exposed to either hourly pulses of monobutyryl cAMP (Bt cAMP, 0.01, 0.1, or 1 mM; 1 mM butyrate pulses to controls), or continuously to forskolin (10 microM). Bt cAMP pulses increased both PRL and alpha-subunit mRNAs, maximal after the 0.1 mM dose for PRL (51% increase vs. butyrate controls) and after the 1 mM dose for alpha (60% increase). However, forskolin was ineffective in increasing PRL or alpha mRNA concentrations. TSH, LH, and FSH beta-subunit mRNAs were not altered by Bt cAMP pulses or forskolin. To confirm the different effects of pulsatile vs. continuous cAMP on PRL and alpha-subunit mRNAs, the response to pulsatile 8-bromo cAMP (1 mM) or Bt cAMP (0.5 mM) was compared to continuous Bt cAMP (0.5 mM). PRL and alpha-subunit mRNAs were increased by both cAMP analogs given in a pulsatile manner but not by continuous Bt cAMP. PRL and LH secretory responses (determined in perifusate samples after 2 h and 22 h of treatment) revealed that both PRL and LH release was increased by cAMP stimulation, given either in a pulsatile or continuous manner. These results show that PRL and alpha-subunit gene expression were sensitive to changes in cAMP stimulation, whereas that of TSH, LH, and FSH beta were unaltered. Only intermittent cAMP stimuli were effective in increasing PRL and alpha mRNAs. These data suggest that pulsatile fluctuations in intracellular cAMP may be essential for maximal expression of the PRL and alpha genes. Thus, intermittent changes in intracellular second messengers may be a necessary part of the pathway involved in the transduction of signals from the plasma membrane to the nucleus."} {"id": "PMID:1280211", "title": "Measurement and characterization of insulin-like growth factor binding protein-3 in human biological fluids: discrepancies between radioimmunoassay and ligand blotting.", "content": "The inability to detect insulin-like growth factor binding protein-3 (IGFBP-3) in some circumstances by Western ligand blot analysis has emphasized the need to characterize IGFBPs by both ligand binding and immunological techniques. In this study, we have: 1) characterized and quantified IGFBP-3 in nonpregnancy, pregnancy, and fetal cord serum, follicular, peritoneal, and amniotic fluid, seminal plasma, cerebrospinal fluid (CSF), and urine; 2) established a new IGFBP-3 RIA that detects both intact and fragments of IGFBP-3; 3) identified both intact and fragments of IGFBP-3 by Western immunoblot techniques; and 4) addressed the discordance between Western ligand blot analysis and RIA by assessing fluids for IGFBP proteolytic activity. All fluids examined, except pregnancy serum, CSF, and amniotic fluid, displayed a 44-34-kilodalton (kDa) IGFBP-3 doublet by Western ligand blot analysis. Western immunoblot analysis using specific IGFBP-3 antiserum showed a 44-34-kDa IGFBP-3 doublet and a 28-kDa fragment in nonpregnancy serum, fetal cord serum, follicular fluid, and peritoneal fluid. The immunoreactive 42-38-kDa doublet was faint in urine and seminal plasma. IGFBPs in CSF did not cross-react with IGFBP-3 antiserum. Pregnancy serum and amniotic fluid contained only the 28-kDa fragment when compared against equal volumes of nonpregnancy serum. With the development of an IGFBP-3 RIA, IGFBP-3 could be accurately measured; urine, CSF, and seminal plasma contained the lowest levels of IGFBP-3 at 27 +/- 3 ng/ml (mean +/- SEM), 110 +/- 26 ng/ml, and 209 +/- 56 ng/ml, respectively. In increasing concentration: fetal cord serum contained 753 +/- 101 ng/ml; peritoneal fluid, 1124 +/- 130 ng/ml; follicular fluid, 2356 +/- 211 ng/ml; nonpregnancy serum, 3556 +/- 508 ng/ml; pregnancy serum, 3718 +/- 842 ng/ml; and amniotic fluid, 5150 +/- 688 ng/ml. The measurable concentrations of IGFBP-3 in CSF and the high concentrations measured in pregnancy serum and amniotic fluid conflicted with Western blot analysis. Thus, fluids were assessed for IGFBP proteolytic activity by incubation with a source of IGFBP-3, either nonpregnancy serum or purified IGFBP-3. All fluids displayed some proteolytic activity with either assay. Fluids with little protease activity (nonpregnancy serum, follicular fluid, and urine) showed a close relationship between immunoassayable IGFBP-3 by RIA and IGFBP-3 band intensity by Western ligand blot. Fluids with high proteolytic activity (pregnancy serum, CSF, seminal plasma, peritoneal fluid, and amniotic fluid) gave discrepant IGFBP-3 values between RIA and Western ligand blot.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Measurement and characterization of insulin-like growth factor binding protein-3 in human biological fluids: discrepancies between radioimmunoassay and ligand blotting. The inability to detect insulin-like growth factor binding protein-3 (IGFBP-3) in some circumstances by Western ligand blot analysis has emphasized the need to characterize IGFBPs by both ligand binding and immunological techniques. In this study, we have: 1) characterized and quantified IGFBP-3 in nonpregnancy, pregnancy, and fetal cord serum, follicular, peritoneal, and amniotic fluid, seminal plasma, cerebrospinal fluid (CSF), and urine; 2) established a new IGFBP-3 RIA that detects both intact and fragments of IGFBP-3; 3) identified both intact and fragments of IGFBP-3 by Western immunoblot techniques; and 4) addressed the discordance between Western ligand blot analysis and RIA by assessing fluids for IGFBP proteolytic activity. All fluids examined, except pregnancy serum, CSF, and amniotic fluid, displayed a 44-34-kilodalton (kDa) IGFBP-3 doublet by Western ligand blot analysis. Western immunoblot analysis using specific IGFBP-3 antiserum showed a 44-34-kDa IGFBP-3 doublet and a 28-kDa fragment in nonpregnancy serum, fetal cord serum, follicular fluid, and peritoneal fluid. The immunoreactive 42-38-kDa doublet was faint in urine and seminal plasma. IGFBPs in CSF did not cross-react with IGFBP-3 antiserum. Pregnancy serum and amniotic fluid contained only the 28-kDa fragment when compared against equal volumes of nonpregnancy serum. With the development of an IGFBP-3 RIA, IGFBP-3 could be accurately measured; urine, CSF, and seminal plasma contained the lowest levels of IGFBP-3 at 27 +/- 3 ng/ml (mean +/- SEM), 110 +/- 26 ng/ml, and 209 +/- 56 ng/ml, respectively. In increasing concentration: fetal cord serum contained 753 +/- 101 ng/ml; peritoneal fluid, 1124 +/- 130 ng/ml; follicular fluid, 2356 +/- 211 ng/ml; nonpregnancy serum, 3556 +/- 508 ng/ml; pregnancy serum, 3718 +/- 842 ng/ml; and amniotic fluid, 5150 +/- 688 ng/ml. The measurable concentrations of IGFBP-3 in CSF and the high concentrations measured in pregnancy serum and amniotic fluid conflicted with Western blot analysis. Thus, fluids were assessed for IGFBP proteolytic activity by incubation with a source of IGFBP-3, either nonpregnancy serum or purified IGFBP-3. All fluids displayed some proteolytic activity with either assay. Fluids with little protease activity (nonpregnancy serum, follicular fluid, and urine) showed a close relationship between immunoassayable IGFBP-3 by RIA and IGFBP-3 band intensity by Western ligand blot. Fluids with high proteolytic activity (pregnancy serum, CSF, seminal plasma, peritoneal fluid, and amniotic fluid) gave discrepant IGFBP-3 values between RIA and Western ligand blot.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1280212", "title": "Non-receptor mediated, post-transcriptional regulation of insulin-like growth factor binding protein (IGFBP)-3 in Hs578T human breast cancer cells.", "content": "Hs578T human breast cancer cells secrete insulin-like growth factor binding protein 3 (IGFBP-3) as the major BP species. In addition, cell surface-associated IGFBP-3 is demonstrable by the use of cell monolayer affinity cross-linking or immunoperoxidase staining of the cell surface with a specific polyclonal anti-human IGFBP-3 antibody (alpha IGFBP-3 gamma 1). In this study, we have demonstrated that regulation of Hs578T IGFBP-3 by IGF peptides is specific, non-receptor mediated, and post-translational by showing: 1) dose-dependent increase of IGFBP-3 in conditioned media (CM) following addition of IGF-I and -II (maximum 13 fold increase at 100 ng/ml), but not by insulin up to 1 mg/ml; 2) no change in CM IGFBP-3 level by [Gln3,Ala4,Tyr15,Leu16] IGF-I, which has decreased affinity for IGFBPs; 3) no change in IGFBP-3 mRNA following addition of IGFs; 4) release of cell surface-associated IGFBP-3 into CM by the addition of IGFs, but not by [Gln3,Ala4,Tyr15,Leu16]IGF-I. These studies demonstrate that IGF peptides regulate CM concentrations of IGFBP-3 through non-receptor mediated dissociation of cell surface-associated IGFBP-3.", "contents": "Non-receptor mediated, post-transcriptional regulation of insulin-like growth factor binding protein (IGFBP)-3 in Hs578T human breast cancer cells. Hs578T human breast cancer cells secrete insulin-like growth factor binding protein 3 (IGFBP-3) as the major BP species. In addition, cell surface-associated IGFBP-3 is demonstrable by the use of cell monolayer affinity cross-linking or immunoperoxidase staining of the cell surface with a specific polyclonal anti-human IGFBP-3 antibody (alpha IGFBP-3 gamma 1). In this study, we have demonstrated that regulation of Hs578T IGFBP-3 by IGF peptides is specific, non-receptor mediated, and post-translational by showing: 1) dose-dependent increase of IGFBP-3 in conditioned media (CM) following addition of IGF-I and -II (maximum 13 fold increase at 100 ng/ml), but not by insulin up to 1 mg/ml; 2) no change in CM IGFBP-3 level by [Gln3,Ala4,Tyr15,Leu16] IGF-I, which has decreased affinity for IGFBPs; 3) no change in IGFBP-3 mRNA following addition of IGFs; 4) release of cell surface-associated IGFBP-3 into CM by the addition of IGFs, but not by [Gln3,Ala4,Tyr15,Leu16]IGF-I. These studies demonstrate that IGF peptides regulate CM concentrations of IGFBP-3 through non-receptor mediated dissociation of cell surface-associated IGFBP-3."} {"id": "PMID:1280213", "title": "The effects of new steroidal anti-androgen, TZP-4238, and chlormadinone acetate on the pituitary, prostate and adrenal gland of the rat: histopathological and immunocytochemical studies.", "content": "The atrophic effects of a synthetic steroidal anti-androgen, TZP-4238, on the pituitary, prostate and adrenal gland of rats were investigated. Male Sprague-Dawley rats were divided into three experimental groups. Group 1 consisted of controls. Groups 2 and 3 received chlormadinone acetate (CMA) 50 mg/kg/day and TZP-4238 10 mg/kg/day p.o., respectively, for 3 weeks. CMA (Group 2) produced marked atrophy of the prostate. Furthermore, CMA caused marked atrophy of the adrenal gland. Histopathologically, the remarkable atrophy was observed in the adrenal cortical cells of zonae fasciculata and reticularis. The most striking ultrastructural alterations were noted in the mitochondria. In addition, intramitochondrial localization of glutathione-peroxidase (GSH-PO) which effectively reduces the lipid peroxides, was less than that in the controls. In the anterior pituitary gland, CMA induced a reduction in the size of ACTH cells. TZP-4238 (Group 3) produced marked atrophy of the prostate. However, TZP-4238 exerted no effect on the adrenal gland or anterior pituitary ACTH cells. In addition, the present histopathological study showed that TZP-4238 or CMA exerted no effect on the testes or anterior pituitary LH cells. Therefore, it is suggested that TZP-4238 causes atrophy of the prostate without any significant histopathological changes in the adrenal glands or anterior pituitary ACTH cells under the present experimental conditions. We further speculated that TZP-4238 had a more potent anti-prostatic effect than CMA and TZP-4238 had a less inhibitory influence than CMA on the pituitary-adrenal axis.", "contents": "The effects of new steroidal anti-androgen, TZP-4238, and chlormadinone acetate on the pituitary, prostate and adrenal gland of the rat: histopathological and immunocytochemical studies. The atrophic effects of a synthetic steroidal anti-androgen, TZP-4238, on the pituitary, prostate and adrenal gland of rats were investigated. Male Sprague-Dawley rats were divided into three experimental groups. Group 1 consisted of controls. Groups 2 and 3 received chlormadinone acetate (CMA) 50 mg/kg/day and TZP-4238 10 mg/kg/day p.o., respectively, for 3 weeks. CMA (Group 2) produced marked atrophy of the prostate. Furthermore, CMA caused marked atrophy of the adrenal gland. Histopathologically, the remarkable atrophy was observed in the adrenal cortical cells of zonae fasciculata and reticularis. The most striking ultrastructural alterations were noted in the mitochondria. In addition, intramitochondrial localization of glutathione-peroxidase (GSH-PO) which effectively reduces the lipid peroxides, was less than that in the controls. In the anterior pituitary gland, CMA induced a reduction in the size of ACTH cells. TZP-4238 (Group 3) produced marked atrophy of the prostate. However, TZP-4238 exerted no effect on the adrenal gland or anterior pituitary ACTH cells. In addition, the present histopathological study showed that TZP-4238 or CMA exerted no effect on the testes or anterior pituitary LH cells. Therefore, it is suggested that TZP-4238 causes atrophy of the prostate without any significant histopathological changes in the adrenal glands or anterior pituitary ACTH cells under the present experimental conditions. We further speculated that TZP-4238 had a more potent anti-prostatic effect than CMA and TZP-4238 had a less inhibitory influence than CMA on the pituitary-adrenal axis."} {"id": "PMID:1280214", "title": "ACTH increases expression of c-fos, c-jun and beta-actin genes in the dexamethasone-treated rat adrenals.", "content": "Our recent finding that ACTH increases c-fos mRNA in the adrenal gland of hypophysectomized rats indicates that the gene product FOS may play an important role(s) in mediating the action of ACTH. However, hypophysectomy employed in that study causes the disappearance of trophic hormones other than ACTH and may modify the effect of ACTH. Thus, in the present investigation, dexamethasone-treated rats were used. Since FOS functions only when it dimerizes with JUN (the product of c-jun gene), the changes in the levels of c-fos and c-jun mRNAs were studied together with that of beta-actin mRNA which is also affected by ACTH. Northern blot analysis was employed to determine the mRNA levels. It was demonstrated that ACTH increases the mRNAs coding c-fos and c-jun in the adrenal glands of dexamethasone-treated, ACTH-suppressed rats. The c-fos mRNA was not detectable before ACTH administration. After ACTH administration, the mRNA levels were transiently increased, the maximum level being observed at 30 min after ACTH. At 180 min post ACTH, the level returned to the unstimulated level. The mRNA coding c-jun was detectable before ACTH administration and it also increased rapidly after ACTH with maximal stimulation at 30 min. However, the mRNA level at 180 min post ACTH was still higher than the unstimulated level. The changes in beta-actin mRNA were approximately the same as those of c-jun mRNA. These results suggest that increased expression of c-fos, c-jun and beta-actin genes by ACTH may play an important role in mediating its action on the adrenals.", "contents": "ACTH increases expression of c-fos, c-jun and beta-actin genes in the dexamethasone-treated rat adrenals. Our recent finding that ACTH increases c-fos mRNA in the adrenal gland of hypophysectomized rats indicates that the gene product FOS may play an important role(s) in mediating the action of ACTH. However, hypophysectomy employed in that study causes the disappearance of trophic hormones other than ACTH and may modify the effect of ACTH. Thus, in the present investigation, dexamethasone-treated rats were used. Since FOS functions only when it dimerizes with JUN (the product of c-jun gene), the changes in the levels of c-fos and c-jun mRNAs were studied together with that of beta-actin mRNA which is also affected by ACTH. Northern blot analysis was employed to determine the mRNA levels. It was demonstrated that ACTH increases the mRNAs coding c-fos and c-jun in the adrenal glands of dexamethasone-treated, ACTH-suppressed rats. The c-fos mRNA was not detectable before ACTH administration. After ACTH administration, the mRNA levels were transiently increased, the maximum level being observed at 30 min after ACTH. At 180 min post ACTH, the level returned to the unstimulated level. The mRNA coding c-jun was detectable before ACTH administration and it also increased rapidly after ACTH with maximal stimulation at 30 min. However, the mRNA level at 180 min post ACTH was still higher than the unstimulated level. The changes in beta-actin mRNA were approximately the same as those of c-jun mRNA. These results suggest that increased expression of c-fos, c-jun and beta-actin genes by ACTH may play an important role in mediating its action on the adrenals."} {"id": "PMID:1280215", "title": "Structures of high-mannose and complex oligosaccharides of mouse TSH and free alpha-subunits after in vitro incubation of thyrotropic tissue with TRH.", "content": "To determine whether incubation of mouse thyrotropic tissue with TRH in vitro influenced the oligosaccharide structure of TSH, thyrotropic tumor tissue or pituitary tissue was incubated in vitro with [3H]mannose or with [35S]sulfate and [3H]methionine, in the absence or presence of TRH for times up to 24 h. [3H]mannose-labeled oligosaccharides from intracellular TSH and free alpha-subunits were analyzed by paper chromatography, and were predominantly Man9GlcNAc and Man8GlcNAc units both in the absence and presence of TRH. The [35S]sulfate/[3H]methionine ratio in secreted molecules was greater for TSH than for free alpha-subunits; within TSH heterodimers the ratio was greater for beta-subunits than alpha-subunits. The [35S]/[3H] ratio was not altered in TSH or free alpha-subunits by TRH. Analyses of [3H]mannose-labeled charged oligosaccharides by HPLC anion-exchange chromatography revealed similar types of oligosaccharides present on TSH subunits and free alpha-subunits (having one or two sulfate residues, one or two sialic acid residues, or both a sulfate and a sialic acid residue). These charged oligosaccharides occurred in different proportions on TSH subunits compared to free alpha-subunits, and also differed depending on whether the tissue source was tumorous or nontumorous. The proportions of oligosaccharide unit types were not altered by TRH. Thus, while this study provided information concerning the high-mannose and complex oligosaccharides of mouse TSH, there was no evidence that short incubations of tissues with TRH in vitro caused modulation of TSH oligosaccharide structures.", "contents": "Structures of high-mannose and complex oligosaccharides of mouse TSH and free alpha-subunits after in vitro incubation of thyrotropic tissue with TRH. To determine whether incubation of mouse thyrotropic tissue with TRH in vitro influenced the oligosaccharide structure of TSH, thyrotropic tumor tissue or pituitary tissue was incubated in vitro with [3H]mannose or with [35S]sulfate and [3H]methionine, in the absence or presence of TRH for times up to 24 h. [3H]mannose-labeled oligosaccharides from intracellular TSH and free alpha-subunits were analyzed by paper chromatography, and were predominantly Man9GlcNAc and Man8GlcNAc units both in the absence and presence of TRH. The [35S]sulfate/[3H]methionine ratio in secreted molecules was greater for TSH than for free alpha-subunits; within TSH heterodimers the ratio was greater for beta-subunits than alpha-subunits. The [35S]/[3H] ratio was not altered in TSH or free alpha-subunits by TRH. Analyses of [3H]mannose-labeled charged oligosaccharides by HPLC anion-exchange chromatography revealed similar types of oligosaccharides present on TSH subunits and free alpha-subunits (having one or two sulfate residues, one or two sialic acid residues, or both a sulfate and a sialic acid residue). These charged oligosaccharides occurred in different proportions on TSH subunits compared to free alpha-subunits, and also differed depending on whether the tissue source was tumorous or nontumorous. The proportions of oligosaccharide unit types were not altered by TRH. Thus, while this study provided information concerning the high-mannose and complex oligosaccharides of mouse TSH, there was no evidence that short incubations of tissues with TRH in vitro caused modulation of TSH oligosaccharide structures."} {"id": "PMID:1280216", "title": "The O18 antigens (lipopolysaccharides) of Escherichia coli. Structural characterization of the O18A, O18A1, O18B and O18B1-specific polysaccharides.", "content": "The O-specific polysaccharide moieties (PS) of the O18A, O18A1, O18B, and O18B1 antigens (lipopolysaccharides, LPS) consist of L-rhamnose (Rha), N-acetyl-D-glucosamine, D-galactose, and D-glucose in different molar ratios. By using chemical fragmentation, methylation, as well as one- and two-dimensional NMR spectroscopy, the structures of these polysaccharides were found to be [formula: see text] In O18A-PS and O18A1-PS x = 2, whereas in O18B-PS and in O18B11-PS x = 3. In all four polysaccharides alpha-D-Galp (residue D) is substituted at O-3. This substituent L (residue E) is beta-D-GlcpNAc-(1 in O18A-PS and O18A1-PS and it is alpha-D-Glcp-(1 in O18B-PS and O18B1-PS. Whereas there is no further substituent on the main chain of the O18A and O18B polysaccharides, in O18A1-PS and O18B1-PS the alpha-D-GlcpNAc residue A is substituted with alpha-Glcp-(1 (residue F), which is linked to O-6 in O18A1-PS and to O-4 in O18B1-PS. These results show that the O18 antigen comprises a group of four related LPS (O18A and O18B, with their glucosylated forms O18A1 and O18B1). The results are discussed with respect to epitope definition and biochemical implications.", "contents": "The O18 antigens (lipopolysaccharides) of Escherichia coli. Structural characterization of the O18A, O18A1, O18B and O18B1-specific polysaccharides. The O-specific polysaccharide moieties (PS) of the O18A, O18A1, O18B, and O18B1 antigens (lipopolysaccharides, LPS) consist of L-rhamnose (Rha), N-acetyl-D-glucosamine, D-galactose, and D-glucose in different molar ratios. By using chemical fragmentation, methylation, as well as one- and two-dimensional NMR spectroscopy, the structures of these polysaccharides were found to be [formula: see text] In O18A-PS and O18A1-PS x = 2, whereas in O18B-PS and in O18B11-PS x = 3. In all four polysaccharides alpha-D-Galp (residue D) is substituted at O-3. This substituent L (residue E) is beta-D-GlcpNAc-(1 in O18A-PS and O18A1-PS and it is alpha-D-Glcp-(1 in O18B-PS and O18B1-PS. Whereas there is no further substituent on the main chain of the O18A and O18B polysaccharides, in O18A1-PS and O18B1-PS the alpha-D-GlcpNAc residue A is substituted with alpha-Glcp-(1 (residue F), which is linked to O-6 in O18A1-PS and to O-4 in O18B1-PS. These results show that the O18 antigen comprises a group of four related LPS (O18A and O18B, with their glucosylated forms O18A1 and O18B1). The results are discussed with respect to epitope definition and biochemical implications."} {"id": "PMID:1280217", "title": "The primary sequence and the subunit structure of mouse alpha-2-macroglobulin, deduced from protein sequencing of the isolated subunits and from molecular cloning of the cDNA.", "content": "Mouse plasma alpha-2-macroglobulin (m alpha 2M) was isolated and the N-terminal amino-acid sequences determined after separation of the 165-kDa and 35-kDa subunits. These sequences were compared to the protein sequence predicted by the cDNA, which was cloned from a mouse liver library and sequenced. From these data it is evident that both subunits are encoded by one mRNA of approximately 5 kb expressed predominantly in liver. The smaller subunit, with the N-terminal sequence DLSSSDLT, comprises the C-terminal 257 residues of m alpha 2M and is derived from a single-chain precursor probably by proteolytic processing at an arginine residue in the sequence PTRDLSS. Analysis of the predicted protein further showed all the salient features of a proteinase inhibitor of the macroglobulin family: a bait region that deviates from all known sequences in this family, a very conserved internal thiolester site and conserved cysteine residues and putative N-glycosylation sites. The synthesis of m alpha 2M in adult liver was demonstrated by Northern blotting and in fetal liver by in-situ hybridization. Transient transfection of COS cells with the cDNA under control of a viral promoter demonstrated the secretion and partial processing of m alpha 2M in the culture medium. In plasma the level of m alpha 2M was found to be stable as expected for the murine counterpart of human plasma alpha-2-macroglobulin. The possibilities of using the mouse as a genetic model to study this proteinase inhibitor in vivo are discussed.", "contents": "The primary sequence and the subunit structure of mouse alpha-2-macroglobulin, deduced from protein sequencing of the isolated subunits and from molecular cloning of the cDNA. Mouse plasma alpha-2-macroglobulin (m alpha 2M) was isolated and the N-terminal amino-acid sequences determined after separation of the 165-kDa and 35-kDa subunits. These sequences were compared to the protein sequence predicted by the cDNA, which was cloned from a mouse liver library and sequenced. From these data it is evident that both subunits are encoded by one mRNA of approximately 5 kb expressed predominantly in liver. The smaller subunit, with the N-terminal sequence DLSSSDLT, comprises the C-terminal 257 residues of m alpha 2M and is derived from a single-chain precursor probably by proteolytic processing at an arginine residue in the sequence PTRDLSS. Analysis of the predicted protein further showed all the salient features of a proteinase inhibitor of the macroglobulin family: a bait region that deviates from all known sequences in this family, a very conserved internal thiolester site and conserved cysteine residues and putative N-glycosylation sites. The synthesis of m alpha 2M in adult liver was demonstrated by Northern blotting and in fetal liver by in-situ hybridization. Transient transfection of COS cells with the cDNA under control of a viral promoter demonstrated the secretion and partial processing of m alpha 2M in the culture medium. In plasma the level of m alpha 2M was found to be stable as expected for the murine counterpart of human plasma alpha-2-macroglobulin. The possibilities of using the mouse as a genetic model to study this proteinase inhibitor in vivo are discussed."} {"id": "PMID:1280218", "title": "Insulin signalling and regulation of glucokinase gene expression in cultured hepatocytes.", "content": "In cultured rat hepatocytes, transcription of the glucokinase gene is turned on by insulin and turned off by glucagon/cAMP, the latter being the dominant effector system. It is thus possible that in the absence of hormones the gene is maintained in a repressed state by the basal level of cAMP and that insulin turns on transcription by relieving cAMP repression, for instance via activation of a cyclic-nucleotide phosphodiesterase. Three inhibitors of this class of enzymes were tested for their effect on the insulin-dependent induction of the glucokinase gene in hepatocytes. Isobutyl methylxanthine, the prototype inhibitor, abrogated the gene response to insulin, as shown by run-on transcription assay. Among the drugs investigated, Ly186126, a preferential inhibitor of type-III phosphodiesterase, proved the most potent in inhibiting insulin-induced accumulation of glucokinase mRNA. Type-III phosphodiesterase is inhibited by cGMP. Induction of glucokinase mRNA was prevented in hepatocytes challenged with insulin in presence of 8-bromoguanosine-3',5'-phosphate. These results are consistent with the involvement of type-III phosphodiesterase in transduction of the insulin signal to the glucokinase gene. However, we were unable to detect significant decreases in total cellular cAMP level or cAMP-dependent-protein-kinase ratio after the addition of insulin to hepatocytes. Many effects of glucagon are mediated via cAMP-dependent protein-kinase phosphorylation of regulatory proteins and, conversely, insulin effects are often accompanied by protein dephosphorylation. A specific inhibitor of protein phosphatases PP1 and PP2A, okadaic acid, was shown to abolish the transcriptional response of the glucokinase gene to insulin. Thus, interference of insulin with the cAMP signal transduction pathway at several steps may be a critical aspect of insulin action on hepatic glucokinase gene expression. In addition, insulin induction of glucokinase mRNA was suppressed by inhibitors of protein synthesis. The underlying mechanism was a severe inhibition of the transcriptional effect of insulin, rather than mRNA destabilization, as demonstrated by run-on transcription assays with nuclei from cycloheximide-treated or pactamycin-treated cells. Transcription of the glucokinase gene may therefore depend on de novo synthesis of the product of an early-response gene induced by insulin, or may require a short-lived trans-acting or accessory factor of transcription. Alternatively, insulin signalling may be compromised in hepatocytes by a mechanism indirectly related to the arrest of protein synthesis.", "contents": "Insulin signalling and regulation of glucokinase gene expression in cultured hepatocytes. In cultured rat hepatocytes, transcription of the glucokinase gene is turned on by insulin and turned off by glucagon/cAMP, the latter being the dominant effector system. It is thus possible that in the absence of hormones the gene is maintained in a repressed state by the basal level of cAMP and that insulin turns on transcription by relieving cAMP repression, for instance via activation of a cyclic-nucleotide phosphodiesterase. Three inhibitors of this class of enzymes were tested for their effect on the insulin-dependent induction of the glucokinase gene in hepatocytes. Isobutyl methylxanthine, the prototype inhibitor, abrogated the gene response to insulin, as shown by run-on transcription assay. Among the drugs investigated, Ly186126, a preferential inhibitor of type-III phosphodiesterase, proved the most potent in inhibiting insulin-induced accumulation of glucokinase mRNA. Type-III phosphodiesterase is inhibited by cGMP. Induction of glucokinase mRNA was prevented in hepatocytes challenged with insulin in presence of 8-bromoguanosine-3',5'-phosphate. These results are consistent with the involvement of type-III phosphodiesterase in transduction of the insulin signal to the glucokinase gene. However, we were unable to detect significant decreases in total cellular cAMP level or cAMP-dependent-protein-kinase ratio after the addition of insulin to hepatocytes. Many effects of glucagon are mediated via cAMP-dependent protein-kinase phosphorylation of regulatory proteins and, conversely, insulin effects are often accompanied by protein dephosphorylation. A specific inhibitor of protein phosphatases PP1 and PP2A, okadaic acid, was shown to abolish the transcriptional response of the glucokinase gene to insulin. Thus, interference of insulin with the cAMP signal transduction pathway at several steps may be a critical aspect of insulin action on hepatic glucokinase gene expression. In addition, insulin induction of glucokinase mRNA was suppressed by inhibitors of protein synthesis. The underlying mechanism was a severe inhibition of the transcriptional effect of insulin, rather than mRNA destabilization, as demonstrated by run-on transcription assays with nuclei from cycloheximide-treated or pactamycin-treated cells. Transcription of the glucokinase gene may therefore depend on de novo synthesis of the product of an early-response gene induced by insulin, or may require a short-lived trans-acting or accessory factor of transcription. Alternatively, insulin signalling may be compromised in hepatocytes by a mechanism indirectly related to the arrest of protein synthesis."} {"id": "PMID:1280219", "title": "The use of multiple-pin peptide synthesis in an analysis of the continuous epitopes recognised by various anti-(recombinant bovine growth hormone) sera. Comparison with predicted regions of immunogenicity and location within the three-dimensional structure of the molecule.", "content": "A recently developed technology called epitope scanning permits the rapid and accurate delineation of continuous stretches of amino acids in a protein which constitute the sequential epitopes recognised by an antiserum raised to that protein. In the present report, we describe the use of this technique to identify the epitopes in the recombinant bovine growth-hormone (rbGH) molecule recognised by three polyclonal guinea-pig antisera and two polyclonal rabbit antisera. The results obtained show that, for guinea-pig antisera, 3 or 4, very-well-defined major continuous epitopes are present. As would be expected given the intrinsic genetic factors (major histocompatibility restriction, antigen processing and presentation) controlling the immune response in individual animals, subtle differences are evident in the precise location and relative reactivities of these epitopes in different guinea-pig antisera. Nevertheless, there is a large degree of overlap in these epitopes, such that immunodominant regions of the antigen can be clearly delineated. In a structural sense, these epitopes share a common motif in that they are sited in areas of the protein antigen with little secondary structure (loop/coil), although there is some contribution by neighbouring alpha-helices. For the two rabbit antisera, the response tends to be rather more heterogeneous, with recognition of more peptides and less clearly defined epitopes than was the case with the guinea-pig antiserum. Comparison of the four guinea-pig epitopes, identified by our experimental methods with computer predictions for this molecule (Jameson-Wolf antigenic index), indicate that two are strongly predicted, one is weakly predicted and one is not predicted. These observations, together with the displayed intraspecies and interspecies variation clearly indicate the limitations of these predictive methods. In conclusion, we have demonstrated that, despite the expected variation in the exact location of continuous epitopes defined by different anti-rbGH sera, there are large regions of overlap defining immunogenic core regions within the molecule. We believe that studies of this nature, together with further understanding of antigen processing and peptide presentation to immune cells, may have a role to play in the development of candidate peptide vaccines.", "contents": "The use of multiple-pin peptide synthesis in an analysis of the continuous epitopes recognised by various anti-(recombinant bovine growth hormone) sera. Comparison with predicted regions of immunogenicity and location within the three-dimensional structure of the molecule. A recently developed technology called epitope scanning permits the rapid and accurate delineation of continuous stretches of amino acids in a protein which constitute the sequential epitopes recognised by an antiserum raised to that protein. In the present report, we describe the use of this technique to identify the epitopes in the recombinant bovine growth-hormone (rbGH) molecule recognised by three polyclonal guinea-pig antisera and two polyclonal rabbit antisera. The results obtained show that, for guinea-pig antisera, 3 or 4, very-well-defined major continuous epitopes are present. As would be expected given the intrinsic genetic factors (major histocompatibility restriction, antigen processing and presentation) controlling the immune response in individual animals, subtle differences are evident in the precise location and relative reactivities of these epitopes in different guinea-pig antisera. Nevertheless, there is a large degree of overlap in these epitopes, such that immunodominant regions of the antigen can be clearly delineated. In a structural sense, these epitopes share a common motif in that they are sited in areas of the protein antigen with little secondary structure (loop/coil), although there is some contribution by neighbouring alpha-helices. For the two rabbit antisera, the response tends to be rather more heterogeneous, with recognition of more peptides and less clearly defined epitopes than was the case with the guinea-pig antiserum. Comparison of the four guinea-pig epitopes, identified by our experimental methods with computer predictions for this molecule (Jameson-Wolf antigenic index), indicate that two are strongly predicted, one is weakly predicted and one is not predicted. These observations, together with the displayed intraspecies and interspecies variation clearly indicate the limitations of these predictive methods. In conclusion, we have demonstrated that, despite the expected variation in the exact location of continuous epitopes defined by different anti-rbGH sera, there are large regions of overlap defining immunogenic core regions within the molecule. We believe that studies of this nature, together with further understanding of antigen processing and peptide presentation to immune cells, may have a role to play in the development of candidate peptide vaccines."} {"id": "PMID:1280220", "title": "Polyreactive autoantibodies to negatively charged epitopes following Trypanosoma cruzi infection.", "content": "During the course of many human autoimmune diseases, antibodies which recognize negatively charged epitopes on self antigens are detected. Trypanosoma cruzi, an intracellular protozoan parasite capable of infecting a wide variety of vertebrates, is the cause of Chagas disease in humans. Infection with the parasite frequently results in autoimmune and inflammatory pathology. We report here on an affinity-purified population of antibodies that bind to a broad class of antigens that contain runs of acidic amino acids, including tubulin. Although these antibodies can be isolated from both uninfected and T. cruzi chronically infected C3H/He mice, the antibodies from the normal mice (the natural autoantibodies) bind to tubulin poorly at physiological pH, whereas the antibodies isolated from the infected animals bind well at physiological pH. We propose that similar processes may occur in humans following other infections accounting for the detection of antibodies to negatively charged epitopes in a variety of autoimmune diseases.", "contents": "Polyreactive autoantibodies to negatively charged epitopes following Trypanosoma cruzi infection. During the course of many human autoimmune diseases, antibodies which recognize negatively charged epitopes on self antigens are detected. Trypanosoma cruzi, an intracellular protozoan parasite capable of infecting a wide variety of vertebrates, is the cause of Chagas disease in humans. Infection with the parasite frequently results in autoimmune and inflammatory pathology. We report here on an affinity-purified population of antibodies that bind to a broad class of antigens that contain runs of acidic amino acids, including tubulin. Although these antibodies can be isolated from both uninfected and T. cruzi chronically infected C3H/He mice, the antibodies from the normal mice (the natural autoantibodies) bind to tubulin poorly at physiological pH, whereas the antibodies isolated from the infected animals bind well at physiological pH. We propose that similar processes may occur in humans following other infections accounting for the detection of antibodies to negatively charged epitopes in a variety of autoimmune diseases."} {"id": "PMID:1280221", "title": "Functional characterization of a novel anti-B7 monoclonal antibody.", "content": "For optimal activation of T cells, binding of their T cell receptor to antigenic peptides in the context of major histocompatibility complex molecules on antigen-presenting cells (APC) is not sufficient. Accessory signals, provided by accessory cells, are needed to induce proliferation and clonal expansion of normal T cells. It has been shown previously that the B7 molecule, present on the cell surface of activated APC, can provide the second signal by binding to the CD28 molecule on T cells. Here we describe a novel anti-B7 (mAb), B7-24. This mAb binds to a functionally important epitope of the B7 molecule. Fab fragments of B7-24 can almost completely block anti-CD3-induced, B7-dependent T cell proliferation when tested in a model system where purified T cells are co-cultured with 3T6 cells expressing the human Fc gamma RII and human B7, in the presence of anti-CD3 mAb. In contrast, mAb B7-24 is not able to inhibit T cell proliferation in primary mixed lymphocyte reactions where purified T cells are co-cultured with Epstein-Barr virus-transformed B cells. These findings suggest that other cell surface molecules allow for maximal proliferation of T cells in mixed lymphocyte reactions, even when the interaction between B7 and CD28 is blocked by B7-24.", "contents": "Functional characterization of a novel anti-B7 monoclonal antibody. For optimal activation of T cells, binding of their T cell receptor to antigenic peptides in the context of major histocompatibility complex molecules on antigen-presenting cells (APC) is not sufficient. Accessory signals, provided by accessory cells, are needed to induce proliferation and clonal expansion of normal T cells. It has been shown previously that the B7 molecule, present on the cell surface of activated APC, can provide the second signal by binding to the CD28 molecule on T cells. Here we describe a novel anti-B7 (mAb), B7-24. This mAb binds to a functionally important epitope of the B7 molecule. Fab fragments of B7-24 can almost completely block anti-CD3-induced, B7-dependent T cell proliferation when tested in a model system where purified T cells are co-cultured with 3T6 cells expressing the human Fc gamma RII and human B7, in the presence of anti-CD3 mAb. In contrast, mAb B7-24 is not able to inhibit T cell proliferation in primary mixed lymphocyte reactions where purified T cells are co-cultured with Epstein-Barr virus-transformed B cells. These findings suggest that other cell surface molecules allow for maximal proliferation of T cells in mixed lymphocyte reactions, even when the interaction between B7 and CD28 is blocked by B7-24."} {"id": "PMID:1280222", "title": "Cryptic T cell epitopes in polymorphic immunoglobulin regions: evidence for positive repertoire selection during fetal development.", "content": "The adult T cell repertoire is the result of positive and negative intrathymic selective processes. Since non-self antigens are not present in the thymus, self peptides are believed to play a role in the thymic T cell selection. T cell lines raised against a peptide from the second complementarity-determining region (CDR2) of the S107 germ-line immunoglobulin (Ig) do not respond to the intact Ig, indicating that in adult animals this CDR2 epitope is cryptic in the context of intact S107 Ig. To show that the response to self Ig peptide is the result of positive selection, the fetal expression of the S107 germ-line Ig was suppressed by maternal anti-idiotype (Id) injection. Id S107-suppressed mice responded poorly to the CDR2 peptide, indicating that S107 Ig selects positively T cells responding to a polymorphic self epitope. Cross-reactivity of cryptic self Ig with non-self epitopes could be a mechanism to increase the T cell repertoire for foreign antigens.", "contents": "Cryptic T cell epitopes in polymorphic immunoglobulin regions: evidence for positive repertoire selection during fetal development. The adult T cell repertoire is the result of positive and negative intrathymic selective processes. Since non-self antigens are not present in the thymus, self peptides are believed to play a role in the thymic T cell selection. T cell lines raised against a peptide from the second complementarity-determining region (CDR2) of the S107 germ-line immunoglobulin (Ig) do not respond to the intact Ig, indicating that in adult animals this CDR2 epitope is cryptic in the context of intact S107 Ig. To show that the response to self Ig peptide is the result of positive selection, the fetal expression of the S107 germ-line Ig was suppressed by maternal anti-idiotype (Id) injection. Id S107-suppressed mice responded poorly to the CDR2 peptide, indicating that S107 Ig selects positively T cells responding to a polymorphic self epitope. Cross-reactivity of cryptic self Ig with non-self epitopes could be a mechanism to increase the T cell repertoire for foreign antigens."} {"id": "PMID:1280223", "title": "Short peptides assist the folding of free class I heavy chains in solution.", "content": "Previous experiments have shown that short peptides coresponding to naturally processed epitopes of viral antigens can induce a conformational change in the class I heavy chain (HC) to which they bind in the fully assembled molecule. Here, we present evidence that the mechanism for this conformational change may involve binding of peptide to a partially unfolded form of free HC, followed by its subsequent folding. These results may be important for understanding the way in which class I molecules are assembled in vivo, and how certain epitopes are selected for presentation to T cells.", "contents": "Short peptides assist the folding of free class I heavy chains in solution. Previous experiments have shown that short peptides coresponding to naturally processed epitopes of viral antigens can induce a conformational change in the class I heavy chain (HC) to which they bind in the fully assembled molecule. Here, we present evidence that the mechanism for this conformational change may involve binding of peptide to a partially unfolded form of free HC, followed by its subsequent folding. These results may be important for understanding the way in which class I molecules are assembled in vivo, and how certain epitopes are selected for presentation to T cells."} {"id": "PMID:1280224", "title": "Relative roles of decay-accelerating factor, membrane cofactor protein, and CD59 in the protection of human endothelial cells against complement-mediated lysis.", "content": "Human umbilical vein endothelial cells (HUVEC) were found by Western blot analysis to express three membrane-bound C regulatory proteins, decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59. DAF was detected on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a 70-kDa molecule under nonreducing conditions in 2% deoxycholate extracts of HUVEC, MCP as a 63-kDa protein and CD59 as a 20-kDa molecule. Northern blot analysis revealed the presence of two species of mRNA expressed in HUVEC, which hybridized to a cDNA probe specific for DAF, with sizes of about 2.0 kb and 2.7 kb. MCP mRNA was detected at 4.2 kb and a CD59 cDNA probe hybridized with three mRNA species with sizes of about 800, 1400 and 2000 bp. DAF and CD59 were released from the surface of HUVEC by phosphatidylinositol-phospholipase C, demonstrating that both are attached to the cell membrane by means of a glycolipid anchor. The relative contribution of DAF, MCP and CD59 in regulating the sensitivity to lysis of HUVEC by autologous complement was determined by incubation of sensitized endothelial cells with F(ab')2 fragments of polyclonal antibodies raised against these proteins. The susceptibility of sensitized cells to lysis by homologous complement was markedly increased in the presence of F(ab')2 anti-CD59 and to a lesser, but significant, extent in the presence of F(ab')2 anti-DAF. F(ab')2 anti-MCP did not significantly alter the susceptibility of HUVEC to complement-mediated lysis.", "contents": "Relative roles of decay-accelerating factor, membrane cofactor protein, and CD59 in the protection of human endothelial cells against complement-mediated lysis. Human umbilical vein endothelial cells (HUVEC) were found by Western blot analysis to express three membrane-bound C regulatory proteins, decay-accelerating factor (DAF), membrane cofactor protein (MCP) and CD59. DAF was detected on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a 70-kDa molecule under nonreducing conditions in 2% deoxycholate extracts of HUVEC, MCP as a 63-kDa protein and CD59 as a 20-kDa molecule. Northern blot analysis revealed the presence of two species of mRNA expressed in HUVEC, which hybridized to a cDNA probe specific for DAF, with sizes of about 2.0 kb and 2.7 kb. MCP mRNA was detected at 4.2 kb and a CD59 cDNA probe hybridized with three mRNA species with sizes of about 800, 1400 and 2000 bp. DAF and CD59 were released from the surface of HUVEC by phosphatidylinositol-phospholipase C, demonstrating that both are attached to the cell membrane by means of a glycolipid anchor. The relative contribution of DAF, MCP and CD59 in regulating the sensitivity to lysis of HUVEC by autologous complement was determined by incubation of sensitized endothelial cells with F(ab')2 fragments of polyclonal antibodies raised against these proteins. The susceptibility of sensitized cells to lysis by homologous complement was markedly increased in the presence of F(ab')2 anti-CD59 and to a lesser, but significant, extent in the presence of F(ab')2 anti-DAF. F(ab')2 anti-MCP did not significantly alter the susceptibility of HUVEC to complement-mediated lysis."} {"id": "PMID:1280225", "title": "Rescue from anti-IgM-induced programmed cell death by the B cell surface proteins CD20 and CD40.", "content": "Programmed cell death (PCD), or apoptosis, is characterized by several morphologic alterations and eventual cleavage of nuclear DNA into oligonucleo-some-length fragments. We defined a human B cell line, Ramos, that responds with PCD following ligation of surface IgM. Of the DNA in Ramos cells 3%-10% was fragmented as early as 4 h after IgM ligation. Propidium iodide staining demonstrated that 20%-40% of Ramos cells became apoptotic by 18 h and further established that cells transiting into the S phase of the cell cycle were susceptible to PCD. Addition of several agents to the Ramos cells abrogated anti-IgM-induced PCD, including the phorbol 12-myristate 13-acetate (PMA). In contrast to the effect of PMA, the 4 alpha PMA isomer of PMA neither activated protein kinase C (PKC) nor rescued the cells from anti-IgM-induced PCD, confirming a role for PKC in negating apoptosis. To explore the effect of physiologic signals on anti-IgM-induced PCD, antibodies against the CD20 or CD40 molecules were added in concert with anti-IgM. Both CD20 and CD40 synergize with anti-IgM to augment proliferation but neither molecule activates PKC in Ramos cells. Both anti-CD20 and anti-CD40 reduced the number of cells undergoing anti-IgM-induced PCD. Unlike the effect of anti-CD40, addition of anti-CD20 to anti-IgM-stimulated cells negated PCD only in a subset of cells. Maximal rescue occurred following the addition of anti-CD40 and occurred by 4 h and at least up to 20 h of culture. These data show that (a) PCD can be initiated in B cells entering the S phase of the cell cycle, (b) PCD can be triggered by engagement of surface IgM in the absence of ancillary signals or PKC activation, and (c) rescue from PCD can occur by several mechanisms, either PKC dependent or PKC independent.", "contents": "Rescue from anti-IgM-induced programmed cell death by the B cell surface proteins CD20 and CD40. Programmed cell death (PCD), or apoptosis, is characterized by several morphologic alterations and eventual cleavage of nuclear DNA into oligonucleo-some-length fragments. We defined a human B cell line, Ramos, that responds with PCD following ligation of surface IgM. Of the DNA in Ramos cells 3%-10% was fragmented as early as 4 h after IgM ligation. Propidium iodide staining demonstrated that 20%-40% of Ramos cells became apoptotic by 18 h and further established that cells transiting into the S phase of the cell cycle were susceptible to PCD. Addition of several agents to the Ramos cells abrogated anti-IgM-induced PCD, including the phorbol 12-myristate 13-acetate (PMA). In contrast to the effect of PMA, the 4 alpha PMA isomer of PMA neither activated protein kinase C (PKC) nor rescued the cells from anti-IgM-induced PCD, confirming a role for PKC in negating apoptosis. To explore the effect of physiologic signals on anti-IgM-induced PCD, antibodies against the CD20 or CD40 molecules were added in concert with anti-IgM. Both CD20 and CD40 synergize with anti-IgM to augment proliferation but neither molecule activates PKC in Ramos cells. Both anti-CD20 and anti-CD40 reduced the number of cells undergoing anti-IgM-induced PCD. Unlike the effect of anti-CD40, addition of anti-CD20 to anti-IgM-stimulated cells negated PCD only in a subset of cells. Maximal rescue occurred following the addition of anti-CD40 and occurred by 4 h and at least up to 20 h of culture. These data show that (a) PCD can be initiated in B cells entering the S phase of the cell cycle, (b) PCD can be triggered by engagement of surface IgM in the absence of ancillary signals or PKC activation, and (c) rescue from PCD can occur by several mechanisms, either PKC dependent or PKC independent."} {"id": "PMID:1280226", "title": "Cloning of TRAP, a ligand for CD40 on human T cells.", "content": "A cDNA clone, designated TRAP (TNF-related activation protein) was isolated from a collection of T cell activation genes. The polypeptide encoded by a mRNA of approx. 2.3 kb is 261 amino acids long with a calculated M(r) of 29.3 kDa. The structural features predict a type II transmembrane protein, but are also compatible with a secreted form. TRAP is highly similar to an identified murine CD40 ligand both at the cDNA (82.8% identity) and the protein (77.4% identity) levels, and related to tumor necrosis factor/lymphotoxin. Expressed in a murine myeloma, TRAP was identified as a ligand for CD40 by binding to a soluble CD40 construct. TRAP mRNA is expressed in a T cell-specific fashion with a maximum at 8 h after stimulation. The TRAP gene is located in the q26.3-q27.1 region of the X chromosome.", "contents": "Cloning of TRAP, a ligand for CD40 on human T cells. A cDNA clone, designated TRAP (TNF-related activation protein) was isolated from a collection of T cell activation genes. The polypeptide encoded by a mRNA of approx. 2.3 kb is 261 amino acids long with a calculated M(r) of 29.3 kDa. The structural features predict a type II transmembrane protein, but are also compatible with a secreted form. TRAP is highly similar to an identified murine CD40 ligand both at the cDNA (82.8% identity) and the protein (77.4% identity) levels, and related to tumor necrosis factor/lymphotoxin. Expressed in a murine myeloma, TRAP was identified as a ligand for CD40 by binding to a soluble CD40 construct. TRAP mRNA is expressed in a T cell-specific fashion with a maximum at 8 h after stimulation. The TRAP gene is located in the q26.3-q27.1 region of the X chromosome."} {"id": "PMID:1280227", "title": "Viral infection in guinea pigs induces a sustained non-specific airway hyperresponsiveness and morphological changes of the respiratory tract.", "content": "In the present study an animal model is described in which a sustained non-specific airway hyperresponsiveness is induced. Guinea pigs were inoculated intratracheally with parainfluenza type 3 (PI-3) virus or control solution. Two, 4, 8, and 16 days after inoculation the tracheae, bronchi, and lung strips were isolated and mounted in organ baths. Two days after inoculation no difference between the control solution and PI-3 virus group was observed, with respect to the histamine concentration/response curve obtained from tracheae, bronchi and lung strips of the respective groups. However, histamine concentration/response curves were significantly (P less than 0.01) shifted upwards in all parts of the airways 4, 8, and 16 days after PI-3 inoculation as compared with the control solution. The excessive contraction of the trachea was not specific for histamine, since an increase in the maximal response was obtained also for the cholinergic receptor agonist, arecoline on day 4 (32%, P less than 0.05), day 8 (24%, P less than 0.05), and day 16 (28%). Morphological examination of the central airways obtained from control solution-inoculated animals revealed no signs of inflammation. However, 2, 4, and 8 days, but not 16 days, after the viral infection, epithelial damage with loss of cilia and mucus-depleted goblet cells were observed. Thus, morphological changes were not directly associated with changes in airway responsiveness. Histological examination of the peripheral airways revealed an influx of inflammatory cells, as shown by typical lesions of patchy alveolitis and bronchiolitis. Bronchiolar epithelium was variously hyperplastic and dysplastic with degenerative changes, and the lumens of the bronchioli were occluded with mucus and inflammatory cells. In conclusion, the virus-induced airway hyperresponsiveness in guinea pigs shows similarities with the human situation, in which a sustained non-specific airway hyperresponsiveness is observed after a respiratory viral infection. In addition, the hyperresponsiveness seems to be accompanied by an influx of inflammatory cells in the airways but not with other morphological changes.", "contents": "Viral infection in guinea pigs induces a sustained non-specific airway hyperresponsiveness and morphological changes of the respiratory tract. In the present study an animal model is described in which a sustained non-specific airway hyperresponsiveness is induced. Guinea pigs were inoculated intratracheally with parainfluenza type 3 (PI-3) virus or control solution. Two, 4, 8, and 16 days after inoculation the tracheae, bronchi, and lung strips were isolated and mounted in organ baths. Two days after inoculation no difference between the control solution and PI-3 virus group was observed, with respect to the histamine concentration/response curve obtained from tracheae, bronchi and lung strips of the respective groups. However, histamine concentration/response curves were significantly (P less than 0.01) shifted upwards in all parts of the airways 4, 8, and 16 days after PI-3 inoculation as compared with the control solution. The excessive contraction of the trachea was not specific for histamine, since an increase in the maximal response was obtained also for the cholinergic receptor agonist, arecoline on day 4 (32%, P less than 0.05), day 8 (24%, P less than 0.05), and day 16 (28%). Morphological examination of the central airways obtained from control solution-inoculated animals revealed no signs of inflammation. However, 2, 4, and 8 days, but not 16 days, after the viral infection, epithelial damage with loss of cilia and mucus-depleted goblet cells were observed. Thus, morphological changes were not directly associated with changes in airway responsiveness. Histological examination of the peripheral airways revealed an influx of inflammatory cells, as shown by typical lesions of patchy alveolitis and bronchiolitis. Bronchiolar epithelium was variously hyperplastic and dysplastic with degenerative changes, and the lumens of the bronchioli were occluded with mucus and inflammatory cells. In conclusion, the virus-induced airway hyperresponsiveness in guinea pigs shows similarities with the human situation, in which a sustained non-specific airway hyperresponsiveness is observed after a respiratory viral infection. In addition, the hyperresponsiveness seems to be accompanied by an influx of inflammatory cells in the airways but not with other morphological changes."} {"id": "PMID:1280228", "title": "Antagonism of 3,4-methylenedioxymethamphetamine-induced neurotoxicity in rat brain by 1-piperonylpiperazine.", "content": "The effects of 1-piperonylpiperazine and N,alpha-dimethylpiperonylamine, which are weak inhibitors for [3H]5-hydroxytryptamine (5-HT) uptake, on 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity were examined. The reductions of serotonergic parameters in the rat cerebral cortex produced by multiple administration of MDMA (10 mg/kg) were attenuated significantly by coadministration of 6-nitroquipazine (10 mg/kg), paroxetine (10 mg/kg) or 1-piperonylpiperazine (20 mg/kg), but not by N,alpha-dimethylpiperonylamine (20 mg/kg). The present data suggest that 1-piperonylpiperazine might inhibit the MDMA-induced neurotoxicity by effect(s) other than 5-HT uptake inhibition.", "contents": "Antagonism of 3,4-methylenedioxymethamphetamine-induced neurotoxicity in rat brain by 1-piperonylpiperazine. The effects of 1-piperonylpiperazine and N,alpha-dimethylpiperonylamine, which are weak inhibitors for [3H]5-hydroxytryptamine (5-HT) uptake, on 3,4-methylenedioxymethamphetamine (MDMA)-induced neurotoxicity were examined. The reductions of serotonergic parameters in the rat cerebral cortex produced by multiple administration of MDMA (10 mg/kg) were attenuated significantly by coadministration of 6-nitroquipazine (10 mg/kg), paroxetine (10 mg/kg) or 1-piperonylpiperazine (20 mg/kg), but not by N,alpha-dimethylpiperonylamine (20 mg/kg). The present data suggest that 1-piperonylpiperazine might inhibit the MDMA-induced neurotoxicity by effect(s) other than 5-HT uptake inhibition."} {"id": "PMID:1280229", "title": "Epitope mapping of two isoforms of a trans Golgi network specific integral membrane protein TGN38/41.", "content": "TGN38/41 is an integral membrane protein predominantly located in the trans Golgi network (TGN) of rat (NRK) cells. We have used a cDNA expression system to map the epitopes recognised by a panel of antibodies raised to TGN38/41 as a preliminary step in the accurate identification of the region(s) of the molecule responsible for its correct intracellular location. These studies have confirmed the predicted topology of the molecule, and have identified a region in the cytoplasmic domain which is immunologically (and hence potentially functionally) conserved between species.", "contents": "Epitope mapping of two isoforms of a trans Golgi network specific integral membrane protein TGN38/41. TGN38/41 is an integral membrane protein predominantly located in the trans Golgi network (TGN) of rat (NRK) cells. We have used a cDNA expression system to map the epitopes recognised by a panel of antibodies raised to TGN38/41 as a preliminary step in the accurate identification of the region(s) of the molecule responsible for its correct intracellular location. These studies have confirmed the predicted topology of the molecule, and have identified a region in the cytoplasmic domain which is immunologically (and hence potentially functionally) conserved between species."} {"id": "PMID:1280230", "title": "Spleen protein tyrosine kinases TPK-IIB and CSK display different immunoreactivity and opposite specificities toward c-src-derived peptides.", "content": "Polyclonal antibodies have been raised against two synthetic peptides reproducing the 48-64 and 353-369 sequences of CSK, a protein tyrosine kinase implicated in the down-regulation of src-related protein kinases. Both antibodies specifically recognize recombinant CSK and a CSK-related 49 kDa protein tyrosine kinase present in spleen but they do not cross-react with purified TPK-IIB, a spleen protein tyrosine kinase sharing with CSK catalytic activity toward src kinases and incapability to autophosphorylate. CSK and TPK-IIB once resolved from each other by heparin-Sepharose affinity chromatography, display opposite specificities toward synthetic peptides reproducing the sequences around the main phosphoacceptor residues of pp60c-src, namely Tyr-416 and Tyr-527. These data support the view that TPK-IIB and CSK may exert opposite effects on the activity of src-related protein tyrosine kinases.", "contents": "Spleen protein tyrosine kinases TPK-IIB and CSK display different immunoreactivity and opposite specificities toward c-src-derived peptides. Polyclonal antibodies have been raised against two synthetic peptides reproducing the 48-64 and 353-369 sequences of CSK, a protein tyrosine kinase implicated in the down-regulation of src-related protein kinases. Both antibodies specifically recognize recombinant CSK and a CSK-related 49 kDa protein tyrosine kinase present in spleen but they do not cross-react with purified TPK-IIB, a spleen protein tyrosine kinase sharing with CSK catalytic activity toward src kinases and incapability to autophosphorylate. CSK and TPK-IIB once resolved from each other by heparin-Sepharose affinity chromatography, display opposite specificities toward synthetic peptides reproducing the sequences around the main phosphoacceptor residues of pp60c-src, namely Tyr-416 and Tyr-527. These data support the view that TPK-IIB and CSK may exert opposite effects on the activity of src-related protein tyrosine kinases."} {"id": "PMID:1280231", "title": "Serotonin N-acetyltransferase (NAT) induction in mammalian retina: role of cyclic AMP and calcium ions.", "content": "In retinas and pineal glands of rat, rabbit and hen, activities of the penultimate (and key regulatory) enzyme in melatonin biosynthesis, serotonin N-acetyltransferase (NAT), display distinct diurnal variations, with high and low values during dark and light phase of a 12-h dark: 12-h light illumination cycle. Two-hour incubation (during daytime hours in light) of isolated pineal glands of the studied vertebrates, or the retinas, with 50 microM forskolin (plus 100 microM 3-isobutyl-1-methylxanthine, IBMX-a phosphodiesterase inhibitor), and 1 mM dibutyryl-cAMP, markedly increased the tissue NAT activity. The same procedures significantly enhanced the enzyme activity of rat retina in light, however, only during nighttime hours. The forskolin (+ IBMX)-induced increase of NAT activity in rat retina was significantly lower in a calcium-free medium, and substantially enhanced when calcium concentration was raised from 1.3 mM to 3.9 mM. Treatment of rats with IBMX or aminophylline, and rabbits with aminophylline, increased NAT activity in their pineal glands irrespective of the time of the day, whereas both phosphodiesterase inhibitors significantly increased the enzyme activity of rat retina only when injected during the subjective dark hours. It is concluded that, by analogy to vertebrate pineal gland, in vertebrate retina an increase of NAT activity (and consequently melatonin formation), stimulated both physiologically (i. e. at night), or pharmacologically, involves a cAMP- and calcium dependent process of the enzyme induction.", "contents": "Serotonin N-acetyltransferase (NAT) induction in mammalian retina: role of cyclic AMP and calcium ions. In retinas and pineal glands of rat, rabbit and hen, activities of the penultimate (and key regulatory) enzyme in melatonin biosynthesis, serotonin N-acetyltransferase (NAT), display distinct diurnal variations, with high and low values during dark and light phase of a 12-h dark: 12-h light illumination cycle. Two-hour incubation (during daytime hours in light) of isolated pineal glands of the studied vertebrates, or the retinas, with 50 microM forskolin (plus 100 microM 3-isobutyl-1-methylxanthine, IBMX-a phosphodiesterase inhibitor), and 1 mM dibutyryl-cAMP, markedly increased the tissue NAT activity. The same procedures significantly enhanced the enzyme activity of rat retina in light, however, only during nighttime hours. The forskolin (+ IBMX)-induced increase of NAT activity in rat retina was significantly lower in a calcium-free medium, and substantially enhanced when calcium concentration was raised from 1.3 mM to 3.9 mM. Treatment of rats with IBMX or aminophylline, and rabbits with aminophylline, increased NAT activity in their pineal glands irrespective of the time of the day, whereas both phosphodiesterase inhibitors significantly increased the enzyme activity of rat retina only when injected during the subjective dark hours. It is concluded that, by analogy to vertebrate pineal gland, in vertebrate retina an increase of NAT activity (and consequently melatonin formation), stimulated both physiologically (i. e. at night), or pharmacologically, involves a cAMP- and calcium dependent process of the enzyme induction."} {"id": "PMID:1280232", "title": "Lidocaine inhibits prolactin secretion in GH4C1 cells by blocking calcium influx.", "content": "The mechanism of the inhibitory effect of local anesthetics on hormone secretion was studied in the GH4C1 line of rat pituitary tumor-derived cells. Lidocaine between 0.1 and 5 mM exerted significant dose-dependent inhibition on the increment in cytosol Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion induced by 30 mM K+. For both effects the IC50 was 0.25 mM and maximal inhibition occurred at 5 mM. A normal response returned within 20 min after removal of lidocaine from the incubation medium. 1 microM tetrodotoxin had no effect on the 30 mM K+ induced [Ca2+]i transient or PRL secretion, indicating that Na+ channels are not involved in the inhibitory effect of lidocaine. Lidocaine similarly inhibited the [Ca2+]i increment and PRL secretion induced by 30% medium hyposmolarity and 1 microM Bay K 8644. Lidocaine was much less effective in inhibiting secretion induced by 1 microM phorbol 12-myristate 13-acetate (TPA) or 5 microM forskolin. 5 mM procaine produced effects similar to those of lidocaine. Our data suggest that in GH4C1 cells local anesthetics depress secretagogue-induced PRL secretion primarily by blocking Ca2+ influx, probably through L-type Ca2+ channels.", "contents": "Lidocaine inhibits prolactin secretion in GH4C1 cells by blocking calcium influx. The mechanism of the inhibitory effect of local anesthetics on hormone secretion was studied in the GH4C1 line of rat pituitary tumor-derived cells. Lidocaine between 0.1 and 5 mM exerted significant dose-dependent inhibition on the increment in cytosol Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion induced by 30 mM K+. For both effects the IC50 was 0.25 mM and maximal inhibition occurred at 5 mM. A normal response returned within 20 min after removal of lidocaine from the incubation medium. 1 microM tetrodotoxin had no effect on the 30 mM K+ induced [Ca2+]i transient or PRL secretion, indicating that Na+ channels are not involved in the inhibitory effect of lidocaine. Lidocaine similarly inhibited the [Ca2+]i increment and PRL secretion induced by 30% medium hyposmolarity and 1 microM Bay K 8644. Lidocaine was much less effective in inhibiting secretion induced by 1 microM phorbol 12-myristate 13-acetate (TPA) or 5 microM forskolin. 5 mM procaine produced effects similar to those of lidocaine. Our data suggest that in GH4C1 cells local anesthetics depress secretagogue-induced PRL secretion primarily by blocking Ca2+ influx, probably through L-type Ca2+ channels."} {"id": "PMID:1280233", "title": "Alpha-adrenergic inhibition of thyrotropin-releasing hormone-induced prolactin secretion in GH4C1 cells is associated with a depressed rise in intracellular Ca2+.", "content": "alpha-Adrenergic receptors are present on the plasma membrane of normal anterior pituitary cells and alpha-adrenergic agonists may play a role in the secretion of corticotropin (ACTH) and thyrotropin (TSH). However, alpha-adrenergic involvement in prolactin (PRL) secretion is uncertain. We have therefore examined this question in the PRL-secreting clonal rat pituitary tumor-derived GH4C1 cells. Norepinephrine (NE), an alpha-adrenergic agonist, had no effect on basal PRL secretion but abolished thyrotropin-releasing hormone (TRH)-induced PRL secretion in a dose-dependent manner (EC50 100 nM). NE also significantly suppressed the TRH-stimulated rise in [Ca2+]i. Phentolamine (PA), a non-selective alpha-adrenergic antagonist, reversed the inhibitory effect of NE on both the TRH-stimulated PRL secretion and [Ca2+]i rise. NE did not inhibit the rise in PRL secretion or [Ca2+]i induced by depolarizing 30 mM K+, 30% hyposmolarity or BAY K-8644, a specific L-type Ca2+ channel agonist. The inhibitory effect of NE on TRH-induced PRL and [Ca2+]i changes was also present when Ca2+ influx was prevented by removing medium Ca2+ or by blocking L-type Ca2+ channels with 2 microM nifedipine. The TRH-stimulated first-phase rise in [Ca2+]i in GH4C1 cells is believed to result primarily from release of sequestered Ca2+ from an intracellular pool through the activation of inositol 1,4,5-trisphosphate (IP3) and this [Ca2+]i spike stimulates PRL secretion. Our data thus suggest that GH4C1 cells have alpha-adrenergic receptors and that alpha-adrenergic agonists either suppress IP3 generation or block IP3 release of sequestered intracellular Ca2+.", "contents": "Alpha-adrenergic inhibition of thyrotropin-releasing hormone-induced prolactin secretion in GH4C1 cells is associated with a depressed rise in intracellular Ca2+. alpha-Adrenergic receptors are present on the plasma membrane of normal anterior pituitary cells and alpha-adrenergic agonists may play a role in the secretion of corticotropin (ACTH) and thyrotropin (TSH). However, alpha-adrenergic involvement in prolactin (PRL) secretion is uncertain. We have therefore examined this question in the PRL-secreting clonal rat pituitary tumor-derived GH4C1 cells. Norepinephrine (NE), an alpha-adrenergic agonist, had no effect on basal PRL secretion but abolished thyrotropin-releasing hormone (TRH)-induced PRL secretion in a dose-dependent manner (EC50 100 nM). NE also significantly suppressed the TRH-stimulated rise in [Ca2+]i. Phentolamine (PA), a non-selective alpha-adrenergic antagonist, reversed the inhibitory effect of NE on both the TRH-stimulated PRL secretion and [Ca2+]i rise. NE did not inhibit the rise in PRL secretion or [Ca2+]i induced by depolarizing 30 mM K+, 30% hyposmolarity or BAY K-8644, a specific L-type Ca2+ channel agonist. The inhibitory effect of NE on TRH-induced PRL and [Ca2+]i changes was also present when Ca2+ influx was prevented by removing medium Ca2+ or by blocking L-type Ca2+ channels with 2 microM nifedipine. The TRH-stimulated first-phase rise in [Ca2+]i in GH4C1 cells is believed to result primarily from release of sequestered Ca2+ from an intracellular pool through the activation of inositol 1,4,5-trisphosphate (IP3) and this [Ca2+]i spike stimulates PRL secretion. Our data thus suggest that GH4C1 cells have alpha-adrenergic receptors and that alpha-adrenergic agonists either suppress IP3 generation or block IP3 release of sequestered intracellular Ca2+."} {"id": "PMID:1280234", "title": "Luteinizing hormone induction of the cholesterol side-chain cleavage enzyme in cultured immature rat Leydig cells: no role of insulin-like growth factor-I?", "content": "Long-term inductive effects of luteinizing hormone (LH) on cholesterol side-chain cleavage (CSCC) enzyme activity were studied, using cultured Leydig cells isolated from 21-day-old rats. Particular reference was given to the role of insulin-like growth factor-I (IGF-I) as an autocrine or paracrine modulator or as an essential extracellular mediator of LH action. The CSCC enzyme activity was measured using an excess of 22(R)-hydroxycholesterol as substrate to saturate the enzyme, and inhibitors of pregnenolone metabolism to concentrate all the products of the enzyme reaction in pregnenolone. The rate of sterol conversion into pregnenolone (CSCC enzyme activity) reflected the amount of cytochrome P-450scc (P-450scc), as was shown by Western blotting. In cells cultured without LH, the CSCC enzyme activity decreased to 10% on day 7 of the culture period. In the presence of various doses of LH ranging from 0.01 to 100 ng/ml, the CSCC enzyme activity also diminished during the first 3 days of culture, but during the following days, the amount of CSCC enzyme was stimulated by LH. In contrast to the absence of any LH effect on the activity of the CSCC enzyme during the first days of the culture, the endogenous steroid production (no added 22(R)-hydroxycholesterol) could be stimulated at least 10-fold by high doses of LH. When LH (1 ng/ml) was added to cells which had been cultured for 7 days without hormones, CSCC enzyme activity was elevated 8-fold after 4 days of exposure of LH. These effects of LH could be mimicked by dbcAMP (0.5 mM). No evidence could be provided that IGF-I plays any role in the LH induction of the CSCC enzyme; neither the addition of exogenous IGF-I or analogs that do not bind to IGF-I binding proteins (IGFBPs) nor the inactivation of endogenous IGF-I action (through binding to IGFBP and antibodies to IGF-I or via masking of IGF-I receptor by antibodies) could influence the LH induced CSCC enzyme activity. The present data raise the question under which conditions IGF-I is capable of modulating Leydig cell steroidogenesis.", "contents": "Luteinizing hormone induction of the cholesterol side-chain cleavage enzyme in cultured immature rat Leydig cells: no role of insulin-like growth factor-I? Long-term inductive effects of luteinizing hormone (LH) on cholesterol side-chain cleavage (CSCC) enzyme activity were studied, using cultured Leydig cells isolated from 21-day-old rats. Particular reference was given to the role of insulin-like growth factor-I (IGF-I) as an autocrine or paracrine modulator or as an essential extracellular mediator of LH action. The CSCC enzyme activity was measured using an excess of 22(R)-hydroxycholesterol as substrate to saturate the enzyme, and inhibitors of pregnenolone metabolism to concentrate all the products of the enzyme reaction in pregnenolone. The rate of sterol conversion into pregnenolone (CSCC enzyme activity) reflected the amount of cytochrome P-450scc (P-450scc), as was shown by Western blotting. In cells cultured without LH, the CSCC enzyme activity decreased to 10% on day 7 of the culture period. In the presence of various doses of LH ranging from 0.01 to 100 ng/ml, the CSCC enzyme activity also diminished during the first 3 days of culture, but during the following days, the amount of CSCC enzyme was stimulated by LH. In contrast to the absence of any LH effect on the activity of the CSCC enzyme during the first days of the culture, the endogenous steroid production (no added 22(R)-hydroxycholesterol) could be stimulated at least 10-fold by high doses of LH. When LH (1 ng/ml) was added to cells which had been cultured for 7 days without hormones, CSCC enzyme activity was elevated 8-fold after 4 days of exposure of LH. These effects of LH could be mimicked by dbcAMP (0.5 mM). No evidence could be provided that IGF-I plays any role in the LH induction of the CSCC enzyme; neither the addition of exogenous IGF-I or analogs that do not bind to IGF-I binding proteins (IGFBPs) nor the inactivation of endogenous IGF-I action (through binding to IGFBP and antibodies to IGF-I or via masking of IGF-I receptor by antibodies) could influence the LH induced CSCC enzyme activity. The present data raise the question under which conditions IGF-I is capable of modulating Leydig cell steroidogenesis."} {"id": "PMID:1280235", "title": "Pituitary adenylate cyclase polypeptide (PACAP) stimulates cyclic AMP formation in pituitary fibroblasts and 3T3 tumor fibroblasts: lack of enhancement by protein kinase C activation.", "content": "A number of neuropeptides were shown to produce potent mitogenic effects on Swiss 3T3 fibroblasts by activating the phospholipase C pathway. Here we provide evidence for the activation by PACAP of the adenylate cyclase pathway in 3T3, as well as in non-tumoral pituitary fibroblasts, similarly to what was seen in pituitary endocrine cells. In these cells, PACAP triggered elevation of both intracellular and extracellular contents of cAMP and the effect was time- and dose-dependent, with half-maximal stimulations being induced with about 0.1 nM. Following activation of protein kinase C (PKC) by the phorbol ester phorbol 12-myristate 13-acetate (PMA), PACAP-induced cAMP production was amplified in pituitary endocrine cells, but was either unchanged or dampened in 3T3 and pituitary fibroblasts, respectively. Pretreatment of cells with pertussis toxin (PT) failed to change the effect of PMA on PACAP-stimulated adenylate cyclase activity, irrespective of the cell type being used. However, PT dramatically reduced the potentiation by PMA of cAMP production enhanced by forskolin in 3T3 cells. These results provide new evidence pointing to the presence in fibroblasts of receptors for PACAP, coupled to cAMP production, which may play a role in the modulation of the mitogenic signal. They also indicate that, compared with pituitary endocrine cells, PKC activation in fibroblasts differentially affected PACAP-induced cAMP formation and that these effects were unaltered upon inhibition by PT of Gi-like proteins.", "contents": "Pituitary adenylate cyclase polypeptide (PACAP) stimulates cyclic AMP formation in pituitary fibroblasts and 3T3 tumor fibroblasts: lack of enhancement by protein kinase C activation. A number of neuropeptides were shown to produce potent mitogenic effects on Swiss 3T3 fibroblasts by activating the phospholipase C pathway. Here we provide evidence for the activation by PACAP of the adenylate cyclase pathway in 3T3, as well as in non-tumoral pituitary fibroblasts, similarly to what was seen in pituitary endocrine cells. In these cells, PACAP triggered elevation of both intracellular and extracellular contents of cAMP and the effect was time- and dose-dependent, with half-maximal stimulations being induced with about 0.1 nM. Following activation of protein kinase C (PKC) by the phorbol ester phorbol 12-myristate 13-acetate (PMA), PACAP-induced cAMP production was amplified in pituitary endocrine cells, but was either unchanged or dampened in 3T3 and pituitary fibroblasts, respectively. Pretreatment of cells with pertussis toxin (PT) failed to change the effect of PMA on PACAP-stimulated adenylate cyclase activity, irrespective of the cell type being used. However, PT dramatically reduced the potentiation by PMA of cAMP production enhanced by forskolin in 3T3 cells. These results provide new evidence pointing to the presence in fibroblasts of receptors for PACAP, coupled to cAMP production, which may play a role in the modulation of the mitogenic signal. They also indicate that, compared with pituitary endocrine cells, PKC activation in fibroblasts differentially affected PACAP-induced cAMP formation and that these effects were unaltered upon inhibition by PT of Gi-like proteins."} {"id": "PMID:1280236", "title": "Differential tissue regulation of insulin-like growth factor binding proteins in experimental diabetes mellitus in the rat.", "content": "The expression and regulation of IGF-I is tissue-specific in diabetes mellitus in the rat. These studies were designed to examine if similar tissue specificity exists for IGF-BPs in the diabetic milieu. Diabetes mellitus was induced by a single i.p. injection of STZ (100 mg/kg body weight). Rats were treated with either vehicle--insulin, vanadate, or phlorizin for 7-14 days. Tissues were analyzed for IGF-BPs by ligand blotting and by affinity cross-linking and immunoprecipitation. In liver tissue from nondiabetic control rats, multiple forms of IGF-BPs were noted, ranging from 48,000 to 25,000 M(r). In diabetic rat liver tissue, the 25,000-M(r) form was unchanged, whereas the higher M(r) forms (48,000-42,000 M(r)) were decreased, and the 30,000-M(r) form was increased. Insulin therapy of diabetic rats decreased all forms to below control levels. In the kidney tissue of control rats, faint IGF-BP bands were seen at 30,000 and 25,000 M(r). In diabetic rat kidney tissue, the 30,000-M(r) form again was increased (as in liver) and restored to control levels with insulin therapy. In contrast, only a 30,000-M(r) band was seen in control pituitary tissue, which was slightly increased in the diabetic rats and also was decreased below control levels by insulin. In hypothalamus and cerebral cortex tissue, bands at 30,000 and 25,000 M(r) were noted, and neither was altered by diabetes or insulin treatment. Treatment of diabetic rats with vanadate and phlorizin resulted in comparable blood glucose levels, which were only slightly higher than those achieved with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Differential tissue regulation of insulin-like growth factor binding proteins in experimental diabetes mellitus in the rat. The expression and regulation of IGF-I is tissue-specific in diabetes mellitus in the rat. These studies were designed to examine if similar tissue specificity exists for IGF-BPs in the diabetic milieu. Diabetes mellitus was induced by a single i.p. injection of STZ (100 mg/kg body weight). Rats were treated with either vehicle--insulin, vanadate, or phlorizin for 7-14 days. Tissues were analyzed for IGF-BPs by ligand blotting and by affinity cross-linking and immunoprecipitation. In liver tissue from nondiabetic control rats, multiple forms of IGF-BPs were noted, ranging from 48,000 to 25,000 M(r). In diabetic rat liver tissue, the 25,000-M(r) form was unchanged, whereas the higher M(r) forms (48,000-42,000 M(r)) were decreased, and the 30,000-M(r) form was increased. Insulin therapy of diabetic rats decreased all forms to below control levels. In the kidney tissue of control rats, faint IGF-BP bands were seen at 30,000 and 25,000 M(r). In diabetic rat kidney tissue, the 30,000-M(r) form again was increased (as in liver) and restored to control levels with insulin therapy. In contrast, only a 30,000-M(r) band was seen in control pituitary tissue, which was slightly increased in the diabetic rats and also was decreased below control levels by insulin. In hypothalamus and cerebral cortex tissue, bands at 30,000 and 25,000 M(r) were noted, and neither was altered by diabetes or insulin treatment. Treatment of diabetic rats with vanadate and phlorizin resulted in comparable blood glucose levels, which were only slightly higher than those achieved with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280237", "title": "ECM gene expression and its modulation by insulin in diabetic rats.", "content": "The steady-state levels of mRNA encoding for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha 1(I) and alpha 1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression.", "contents": "ECM gene expression and its modulation by insulin in diabetic rats. The steady-state levels of mRNA encoding for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, basement membrane HSPG, and alpha 1(I) and alpha 1(III) collagen chains were examined in rat glomeruli at 4, 12, and 24 wk after injection of STZ. The mRNA levels for the alpha 1(IV) collagen chain, laminin B1 and B2 chains, and alpha 1(I) and alpha 1(III) collagen chains increased significantly with age in the STZ-induced diabetic rats before morphological thickening of basement membrane occurred. In contrast, the mRNA levels for HSPG decreased markedly 4 wk after STZ injection and then increased with age compared with those for control rats. The mRNA levels for these ECM components showed a continuous decline with age in controls. Treating the diabetic rats with insulin for 4 wk ameliorated the abnormally regulated ECM gene expression in the glomeruli. These data suggest that the abnormal regulation of ECM gene expression in the glomeruli may contribute to the expansion of mesangial matrix and basement membrane thickening in diabetic rats, and that hyperglycemia may play a role in the abnormal ECM gene expression."} {"id": "PMID:1280238", "title": "Effects of STZ-induced diabetes and fasting on insulin receptor mRNA expression and insulin receptor gene transcription in rat liver.", "content": "Insulinopenic states in rodents are known to cause an increase in the number of hepatic insulin receptors. To determine if this change is related to an abnormality in insulin receptor gene expression, insulin receptor binding, insulin receptor mRNA levels, and insulin receptor gene transcription rates have been measured in livers from rats rendered hypoinsulinemic by STZ administration (65 mg/kg) or fasting. In the two groups of experimental rats, insulin binding to liver plasma membranes was increased (approximately 40 and 25%, respectively) relative to control, normoinsulinemic animals. Northern blot analysis of either total or poly (A)+ RNA from livers of hypo- and normoinsulinemic rats revealed two major insulin receptor mRNA species of 9.5 and 7.5 kbs. In hypoinsulinemic rats, insulin receptor mRNA levels were increased > or = 10-fold, with similar effects on the two mRNA species. The effects of STZ administration and fasting on insulin receptor binding and insulin receptor mRNA levels were fully reversed by insulin treatment or refeeding, respectively. Injection of ACT D, an inhibitor of gene transcription, decreased insulin receptor mRNA levels by > or = 80% in control and diabetic rats and suppressed the overexpression of mRNA seen in diabetic rats. In vitro nuclear transcription assays showed that the rate of transcription of the insulin receptor gene was increased 2-fold in STZ-induced diabetic rats and fasted rats relative to control animals. Taken together, these results suggest that the upregulation of the insulin receptor induced by chronic insulinopenia results, at least in part, from an increase in insulin receptor gene transcription.", "contents": "Effects of STZ-induced diabetes and fasting on insulin receptor mRNA expression and insulin receptor gene transcription in rat liver. Insulinopenic states in rodents are known to cause an increase in the number of hepatic insulin receptors. To determine if this change is related to an abnormality in insulin receptor gene expression, insulin receptor binding, insulin receptor mRNA levels, and insulin receptor gene transcription rates have been measured in livers from rats rendered hypoinsulinemic by STZ administration (65 mg/kg) or fasting. In the two groups of experimental rats, insulin binding to liver plasma membranes was increased (approximately 40 and 25%, respectively) relative to control, normoinsulinemic animals. Northern blot analysis of either total or poly (A)+ RNA from livers of hypo- and normoinsulinemic rats revealed two major insulin receptor mRNA species of 9.5 and 7.5 kbs. In hypoinsulinemic rats, insulin receptor mRNA levels were increased > or = 10-fold, with similar effects on the two mRNA species. The effects of STZ administration and fasting on insulin receptor binding and insulin receptor mRNA levels were fully reversed by insulin treatment or refeeding, respectively. Injection of ACT D, an inhibitor of gene transcription, decreased insulin receptor mRNA levels by > or = 80% in control and diabetic rats and suppressed the overexpression of mRNA seen in diabetic rats. In vitro nuclear transcription assays showed that the rate of transcription of the insulin receptor gene was increased 2-fold in STZ-induced diabetic rats and fasted rats relative to control animals. Taken together, these results suggest that the upregulation of the insulin receptor induced by chronic insulinopenia results, at least in part, from an increase in insulin receptor gene transcription."} {"id": "PMID:1280239", "title": "Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM.", "content": "Serum levels of recently discovered circulating forms of adhesion molecules, ICAM-1 and L-selectin, were found to be elevated in IDDM patients and in subjects at risk for developing IDDM compared with 100 normal, nondiabetic blood donors. Both adhesion molecules were determined by sandwich ELISA. Serum concentrations of either clCAM-1 or cL-selectin were > 2SD of normal mean in 10 of 14 recent-onset IDDM patients (P < 0.05). Serum levels of clCAM-1 and cL-selectin did not correlate. In first-degree relatives, elevated adhesion molecule levels were observed in the 6 ICA+ individuals and in the ICA- individuals all (n = 14) with a genetic risk of IDDM (sharing HLA-DR3 and/or-DR4 with the diabetic relative) but not in the HLA-DR3- and/or -DR4- relatives (n = 13). We conclude that elevated clCAM-1 and cL-selectin levels occur independently of ICA status and probably reflect ongoing immune processes in recent-onset IDDM patients and first-degree relatives at risk for IDDM.", "contents": "Elevated levels of circulating adhesion molecules in IDDM patients and in subjects at risk for IDDM. Serum levels of recently discovered circulating forms of adhesion molecules, ICAM-1 and L-selectin, were found to be elevated in IDDM patients and in subjects at risk for developing IDDM compared with 100 normal, nondiabetic blood donors. Both adhesion molecules were determined by sandwich ELISA. Serum concentrations of either clCAM-1 or cL-selectin were > 2SD of normal mean in 10 of 14 recent-onset IDDM patients (P < 0.05). Serum levels of clCAM-1 and cL-selectin did not correlate. In first-degree relatives, elevated adhesion molecule levels were observed in the 6 ICA+ individuals and in the ICA- individuals all (n = 14) with a genetic risk of IDDM (sharing HLA-DR3 and/or-DR4 with the diabetic relative) but not in the HLA-DR3- and/or -DR4- relatives (n = 13). We conclude that elevated clCAM-1 and cL-selectin levels occur independently of ICA status and probably reflect ongoing immune processes in recent-onset IDDM patients and first-degree relatives at risk for IDDM."} {"id": "PMID:1280240", "title": "Recombinant HIV-1 nucleocapsid protein p15 produced as a fusion protein with glutathione S-transferase in Escherichia coli mediates dimerization and enhances reverse transcription of retroviral RNA.", "content": "Human immunodeficiency virus 1 (HIV-1) nucleocapsid protein p15 was produced as a fusion protein with glutathione S-transferase (GST) in Escherichia coli. Rapid purification of GST::p15 in an active form by one-step glutathione-agarose chromatography was accomplished in the presence of an antioxidant. Recombinant p15 fused to GST was shown to stimulate the dimerization of viral RNA. HIV-1 reverse transcriptase-catalyzed in vitro synthesis of minus-strand cDNA from synthetic human tRNA(Lys3UUU) and natural bovine tRNA(Lys3SUU) primer molecules was enhanced by GST::p15. GST produced in E.coli revealed no effect with respect to RNA dimerization and cDNA synthesis, demonstrating that both activities reside in the p15 portion of the fusion protein.", "contents": "Recombinant HIV-1 nucleocapsid protein p15 produced as a fusion protein with glutathione S-transferase in Escherichia coli mediates dimerization and enhances reverse transcription of retroviral RNA. Human immunodeficiency virus 1 (HIV-1) nucleocapsid protein p15 was produced as a fusion protein with glutathione S-transferase (GST) in Escherichia coli. Rapid purification of GST::p15 in an active form by one-step glutathione-agarose chromatography was accomplished in the presence of an antioxidant. Recombinant p15 fused to GST was shown to stimulate the dimerization of viral RNA. HIV-1 reverse transcriptase-catalyzed in vitro synthesis of minus-strand cDNA from synthetic human tRNA(Lys3UUU) and natural bovine tRNA(Lys3SUU) primer molecules was enhanced by GST::p15. GST produced in E.coli revealed no effect with respect to RNA dimerization and cDNA synthesis, demonstrating that both activities reside in the p15 portion of the fusion protein."} {"id": "PMID:1280241", "title": "Constitutive and inducible factors bind to regulatory element 3 in the promoter of the gene encoding mouse granulocyte colony-stimulating factor.", "content": "The expression of the mouse gene (G-CSF) encoding granulocyte colony-stimulating factor is controlled by at least three regulatory elements, GPE1, GPE2 and GPE3 (G-CSF promoter elements). A set of 30-mer oligodeoxyribonucleotides (oligos) scanning the GPE3 region (-104 to -51) of the G-CSF promoter was synthesized, and the tetramer of each oligo was inserted upstream from the cat gene with the simian virus 40 enhancer element. By introducing these hybrid genes into human squamous carcinoma CHU-2 and mouse macrophage BAM3 cells, the enhancer core element of the GPE3 was localized to the region from -98 to -79 in the promoter. A nuclear factor which specifically binds to the core element of the GPE3 was constitutively detected in human CHU-2 cells, whereas the expression of a similar, but distinctly different, factor was significantly induced in BAM3 cells by lipopolysaccharide. The results suggest that these nuclear factors play important roles in the constitutive expression of G-CSF in CHU-2 cells and its inducible expression in macrophages.", "contents": "Constitutive and inducible factors bind to regulatory element 3 in the promoter of the gene encoding mouse granulocyte colony-stimulating factor. The expression of the mouse gene (G-CSF) encoding granulocyte colony-stimulating factor is controlled by at least three regulatory elements, GPE1, GPE2 and GPE3 (G-CSF promoter elements). A set of 30-mer oligodeoxyribonucleotides (oligos) scanning the GPE3 region (-104 to -51) of the G-CSF promoter was synthesized, and the tetramer of each oligo was inserted upstream from the cat gene with the simian virus 40 enhancer element. By introducing these hybrid genes into human squamous carcinoma CHU-2 and mouse macrophage BAM3 cells, the enhancer core element of the GPE3 was localized to the region from -98 to -79 in the promoter. A nuclear factor which specifically binds to the core element of the GPE3 was constitutively detected in human CHU-2 cells, whereas the expression of a similar, but distinctly different, factor was significantly induced in BAM3 cells by lipopolysaccharide. The results suggest that these nuclear factors play important roles in the constitutive expression of G-CSF in CHU-2 cells and its inducible expression in macrophages."} {"id": "PMID:1280242", "title": "Benign prostatic hyperplasia: drug and nondrug therapies.", "content": "Benign prostatic hyperplasia (BPH) is a frequent finding in older men. Patients with symptoms have traditionally been treated with transurethral resection of the prostate, a surgical technique that effectively reduces infravesical obstruction. Nonsurgical management of BPH also has the potential to play an important role in the treatment of patients with moderate or severe symptoms or in those who do not elect surgery. Data are being evaluated to determine the efficacy of treating symptomatic BPH with such modalities as balloon dilation, prostate hyperthermia, androgen suppression, the 5-alpha reductase inhibitor finasteride, and selective alpha blockers.", "contents": "Benign prostatic hyperplasia: drug and nondrug therapies. Benign prostatic hyperplasia (BPH) is a frequent finding in older men. Patients with symptoms have traditionally been treated with transurethral resection of the prostate, a surgical technique that effectively reduces infravesical obstruction. Nonsurgical management of BPH also has the potential to play an important role in the treatment of patients with moderate or severe symptoms or in those who do not elect surgery. Data are being evaluated to determine the efficacy of treating symptomatic BPH with such modalities as balloon dilation, prostate hyperthermia, androgen suppression, the 5-alpha reductase inhibitor finasteride, and selective alpha blockers."} {"id": "PMID:1280243", "title": "Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis.", "content": "Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma.", "contents": "Occurrence of oval-type cells in hepatitis B virus-associated human hepatocarcinogenesis. Proliferation of a new population of epithelial cells with distinct structure, as well as cytokeratin and alpha-fetoprotein expression, was observed in nonneoplastic liver tissues from 14 cases (13 hepatitis B virus-positive) of human hepatocellular carcinoma. These cells were characterized by oval nuclei; scant, pale cytoplasm; small cell size; and cross-reaction with a monoclonal antibody against rat oval cells. These putative human oval cells were strongly positive for cytokeratin 19 and displayed considerable heterogeneity in alpha-fetoprotein and albumin expression. The oval cells were most prominent in actively regenerating nodules and in liver tissue surrounding the cancer. Oval cells and transitional types of cells appear to be the principal producers of alpha-fetoprotein in the regenerating liver. Cancer cells positive for cytokeratins 8, 18 and 19 were observed in half the hepatocellular carcinomas studied. The data suggest that a new cell population structurally similar to oval cells seen in early stages of chemical hepatocarcinogenesis in rats is consistently present in regenerating liver lesions associated with human hepatocellular carcinoma. Furthermore, it is possible that the proliferation of these oval-type cells may partly account for the elevation of serum alpha-fetoprotein frequently seen in precancerous stages of hepatitis B virus-associated human hepatocellular carcinoma."} {"id": "PMID:1280244", "title": "Multiple autoepitope presentation for specific detection of antibodies in primary biliary cirrhosis.", "content": "Antimitochondrial autoantibodies are present in sera from close to 95% of patients with primary biliary cirrhosis. The so-called primary biliary cirrhosis-specific antigen, named M2, was found to be associated with an enzyme complex of the inner mitochondrial membrane and, more precisely, with the E2 component, dihydrolipoamide acetyltransferase, of the pyruvate dehydrogenase complex. We recently established that an immunodominant epitope recognized in direct enzyme-linked immunosorbent assay by primary biliary cirrhosis M2+ sera, but not by non-primary biliary cirrhosis M2+ sera, could be mimicked by a synthetic peptide encompassing residues 167-184 of the E2 component and associated with lipoic acid. This fragment is present in the natural inner lipoyl-binding site of the human enzyme, and the presence of lipoic acid located on lysine 173 was found to be essential to allow IgG antibody binding. In this study we have improved the enzyme-linked immunosorbent assay test based on the synthetic peptide-lipoic acid conjugate by using a multiple antigen peptide system containing eight copies of the peptide as antigen. This approach avoids the use of a peptide conjugated to a carrier protein and was found to be particularly efficient because 23 of 27 primary biliary cirrhosis M2+ sera (85%) could be identified. A multiple antigen peptide without lipoic acid was not recognized by primary biliary cirrhosis antibodies. The peptide used in the multiple antigen peptide construction was a short 13-mer peptide encompassing a highly conserved sequence present in both the outer (residues 40-52) and the inner (residues 167-179) lipoyl-binding sites of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Multiple autoepitope presentation for specific detection of antibodies in primary biliary cirrhosis. Antimitochondrial autoantibodies are present in sera from close to 95% of patients with primary biliary cirrhosis. The so-called primary biliary cirrhosis-specific antigen, named M2, was found to be associated with an enzyme complex of the inner mitochondrial membrane and, more precisely, with the E2 component, dihydrolipoamide acetyltransferase, of the pyruvate dehydrogenase complex. We recently established that an immunodominant epitope recognized in direct enzyme-linked immunosorbent assay by primary biliary cirrhosis M2+ sera, but not by non-primary biliary cirrhosis M2+ sera, could be mimicked by a synthetic peptide encompassing residues 167-184 of the E2 component and associated with lipoic acid. This fragment is present in the natural inner lipoyl-binding site of the human enzyme, and the presence of lipoic acid located on lysine 173 was found to be essential to allow IgG antibody binding. In this study we have improved the enzyme-linked immunosorbent assay test based on the synthetic peptide-lipoic acid conjugate by using a multiple antigen peptide system containing eight copies of the peptide as antigen. This approach avoids the use of a peptide conjugated to a carrier protein and was found to be particularly efficient because 23 of 27 primary biliary cirrhosis M2+ sera (85%) could be identified. A multiple antigen peptide without lipoic acid was not recognized by primary biliary cirrhosis antibodies. The peptide used in the multiple antigen peptide construction was a short 13-mer peptide encompassing a highly conserved sequence present in both the outer (residues 40-52) and the inner (residues 167-179) lipoyl-binding sites of the enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280245", "title": "Increase of cytokeratin D during liver regeneration: association with the nuclear matrix.", "content": "An increase of a 45 kD protein (p45) in the nuclear matrix has been observed when rat liver cells were proliferatively activated in vivo by a partial hepatectomy. The maximal levels of the association of p45 with the nuclear matrix have been detected 24 hr after hepatectomy just at the time when DNA replication is also maximal. By amino acid sequence analysis, immunoblotting and immunocytochemical methods, it has been demonstrated that p45 is identical to rat cytokeratin D. Immunogold staining of nuclear matrix-intermediate filament preparations from cultured hepatocytes indicated that p45 is associated with cytoskeletal filaments that are strongly interconnected to the lamina, whereas no intranuclear localization of the protein has been detected. With an overlay assay a specific binding of labeled p45 to two nonidentified high-molecular weight proteins and also to lamin B has been observed. Northern blot analysis revealed a biphasic pattern of expression of the messenger RNA for cytokeratin D during liver regeneration. A sharp increase in the messenger RNA levels occurred in the prereplicative phase of liver regeneration a few hours before the accumulation of the protein in the nuclear matrix fraction, and a second peak occurred 48 hr after partial hepatectomy.", "contents": "Increase of cytokeratin D during liver regeneration: association with the nuclear matrix. An increase of a 45 kD protein (p45) in the nuclear matrix has been observed when rat liver cells were proliferatively activated in vivo by a partial hepatectomy. The maximal levels of the association of p45 with the nuclear matrix have been detected 24 hr after hepatectomy just at the time when DNA replication is also maximal. By amino acid sequence analysis, immunoblotting and immunocytochemical methods, it has been demonstrated that p45 is identical to rat cytokeratin D. Immunogold staining of nuclear matrix-intermediate filament preparations from cultured hepatocytes indicated that p45 is associated with cytoskeletal filaments that are strongly interconnected to the lamina, whereas no intranuclear localization of the protein has been detected. With an overlay assay a specific binding of labeled p45 to two nonidentified high-molecular weight proteins and also to lamin B has been observed. Northern blot analysis revealed a biphasic pattern of expression of the messenger RNA for cytokeratin D during liver regeneration. A sharp increase in the messenger RNA levels occurred in the prereplicative phase of liver regeneration a few hours before the accumulation of the protein in the nuclear matrix fraction, and a second peak occurred 48 hr after partial hepatectomy."} {"id": "PMID:1280246", "title": "Rapid and marked induction of hepatocyte growth factor during liver regeneration after ischemic or crush injury.", "content": "Liver injuries induced by ischemia or physical trauma are characterized by noninflammatory damage frequently observed in a clinical setting. When the liver of rats was injured by ischemic treatment or physical crushing, necrotic tissue degeneration occurred in several sites of lobulus within 24 hr. Hepatocyte growth factor, a potent mitogen for adult rat hepatocytes in primary culture, was markedly induced in the livers of rats injured by ischemia or physical trauma. In both cases, the hepatocyte growth factor messenger RNA level in the injured liver reached about 10 to 20 times that of the normal level during 12 to 24 hr after liver injury. The increase in hepatocyte growth factor messenger RNA correlated well with the degree of liver damage as evaluated by serum ALT activity in the sera of rats. In situ hybridization showed that hepatocyte growth factor messenger RNA expression occurs in nonparenchymal liver cells, primarily in Kupffer cells of the ischemic liver. After the increase of hepatocyte growth factor messenger RNA in the injured liver, a marked compensatory hepatocyte DNA synthesis occurred 48 to 72 hr after these treatments. These results suggest that hepatocyte growth factor acts as a hepatotropic factor for liver regeneration after noninflammatory liver damage caused by ischemia and physical crush, probably through a paracrine mechanism.", "contents": "Rapid and marked induction of hepatocyte growth factor during liver regeneration after ischemic or crush injury. Liver injuries induced by ischemia or physical trauma are characterized by noninflammatory damage frequently observed in a clinical setting. When the liver of rats was injured by ischemic treatment or physical crushing, necrotic tissue degeneration occurred in several sites of lobulus within 24 hr. Hepatocyte growth factor, a potent mitogen for adult rat hepatocytes in primary culture, was markedly induced in the livers of rats injured by ischemia or physical trauma. In both cases, the hepatocyte growth factor messenger RNA level in the injured liver reached about 10 to 20 times that of the normal level during 12 to 24 hr after liver injury. The increase in hepatocyte growth factor messenger RNA correlated well with the degree of liver damage as evaluated by serum ALT activity in the sera of rats. In situ hybridization showed that hepatocyte growth factor messenger RNA expression occurs in nonparenchymal liver cells, primarily in Kupffer cells of the ischemic liver. After the increase of hepatocyte growth factor messenger RNA in the injured liver, a marked compensatory hepatocyte DNA synthesis occurred 48 to 72 hr after these treatments. These results suggest that hepatocyte growth factor acts as a hepatotropic factor for liver regeneration after noninflammatory liver damage caused by ischemia and physical crush, probably through a paracrine mechanism."} {"id": "PMID:1280247", "title": "Murine ascitic fluids contain varying amounts of an inhibitor that interferes with complement-mediated effector functions of monoclonal antibodies.", "content": "The ability of murine monoclonal antibodies (mAbs), directed to the inner core of Gram-negative bacterial lipopolysaccharide (LPS, endotoxin), to enhance complement-mediated killing of bacteria, was investigated. The mAbs were tested as present in ascitic fluid. It was found that ascites contains an factor that inhibited the activity of complement. This effect was evident in assays for complement-mediated lysis of antibody-coated Gram-negative bacteria (bacterial killing) or of opsonised red blood cells. Moreover, the amount of inhibitor was found to vary from one ascites to another and spanned a 60-fold range. Thus, in vitro or in vivo experiments where complement is known to play a determining role may yield incorrect results when ascites is used as a source of antibody; the use of ascites prepared from irrelevant antibody as a negative control does not eliminate this problem.", "contents": "Murine ascitic fluids contain varying amounts of an inhibitor that interferes with complement-mediated effector functions of monoclonal antibodies. The ability of murine monoclonal antibodies (mAbs), directed to the inner core of Gram-negative bacterial lipopolysaccharide (LPS, endotoxin), to enhance complement-mediated killing of bacteria, was investigated. The mAbs were tested as present in ascitic fluid. It was found that ascites contains an factor that inhibited the activity of complement. This effect was evident in assays for complement-mediated lysis of antibody-coated Gram-negative bacteria (bacterial killing) or of opsonised red blood cells. Moreover, the amount of inhibitor was found to vary from one ascites to another and spanned a 60-fold range. Thus, in vitro or in vivo experiments where complement is known to play a determining role may yield incorrect results when ascites is used as a source of antibody; the use of ascites prepared from irrelevant antibody as a negative control does not eliminate this problem."} {"id": "PMID:1280248", "title": "Monoclonal antibodies against Salmonella porins: generation and characterization.", "content": "Monoclonal antibodies (mAbs) were generated against porins, one of the major outer membrane proteins of Salmonella typhi. Six clones, designated MP1, MP2, MP3 (IgG2ak), MPN4, MPN6 (IgG1k) and MPN5 (IgG2bk) were characterized by enzyme immunoassay (ELISA) for their reactivity to porins from S. typhi, Salmonella paratyphi A, S. paratyphi B, S. paratyphi C, Salmonella choleraesuis, Salmonella enteritidis, Salmonella krefeld, Salmonella panama, Salmonella typhimurium, Escherichia coli B, Shigella flexneri 1b and Pseudomonas aeruginosa. All the clones positive for S. typhi porins showed varying reactivity towards several Salmonella species. However, none of them was positive for porins from other Gram-negative bacteria or for lipopolysaccharide (LPS). The affinity constant of these mAbs, except MPN4, was found to be in the higher range. Dot ELISA revealed that the mAbs recognized porins only in their native form. The results of inhibition ELISA using horseradish peroxidase (HRP)-conjugated MP1 suggest that the clones MP1, MP2, MP3, MPN5 and MPN6 secreted antibodies to identical epitope(s) of a 36-kDa peptide and MPN4 to a different epitope of a 35-kDa peptide. The possible applications of these mAbs were discussed.", "contents": "Monoclonal antibodies against Salmonella porins: generation and characterization. Monoclonal antibodies (mAbs) were generated against porins, one of the major outer membrane proteins of Salmonella typhi. Six clones, designated MP1, MP2, MP3 (IgG2ak), MPN4, MPN6 (IgG1k) and MPN5 (IgG2bk) were characterized by enzyme immunoassay (ELISA) for their reactivity to porins from S. typhi, Salmonella paratyphi A, S. paratyphi B, S. paratyphi C, Salmonella choleraesuis, Salmonella enteritidis, Salmonella krefeld, Salmonella panama, Salmonella typhimurium, Escherichia coli B, Shigella flexneri 1b and Pseudomonas aeruginosa. All the clones positive for S. typhi porins showed varying reactivity towards several Salmonella species. However, none of them was positive for porins from other Gram-negative bacteria or for lipopolysaccharide (LPS). The affinity constant of these mAbs, except MPN4, was found to be in the higher range. Dot ELISA revealed that the mAbs recognized porins only in their native form. The results of inhibition ELISA using horseradish peroxidase (HRP)-conjugated MP1 suggest that the clones MP1, MP2, MP3, MPN5 and MPN6 secreted antibodies to identical epitope(s) of a 36-kDa peptide and MPN4 to a different epitope of a 35-kDa peptide. The possible applications of these mAbs were discussed."} {"id": "PMID:1280249", "title": "Antibodies to reverse transcriptase in HIV infection and progression to AIDS.", "content": "Serum antibodies to the reverse transcriptase (ART) of human immunodeficiency virus 1 (HIV-1) were sequentially determined by ELISA in a group of 41 HIV-seropositive male homosexuals and 101 matched healthy controls, over 1.5-6 years (mean follow-up 3.25 years). Mean ART levels were significantly higher in the patient group as compared to the controls (195 +/- 75 vs. 75 +/- 45 absorbance (A) units; P less than 0.05). When analyzed in parallel with clinical evaluation and T-cell subset determinations, a \"surge\" in ART activity was associated with a more favourable course: eleven patients whose ART profile showed an increase greater than 100 A units (mean delta A 159.6 units) showed an attenuated decrease of CD4+ (T helper) lymphocytes with a mean time of 42.5 months to reach a CD4+ number of 400 cells/mm3. In contrast, 25 matched seropositive patients whose ART remained constant became CD4+ less than 400 cells/mm3 within a mean time of 10.8 months (P less than 0.05). These results as well as individual patients' data support a surge in serum ART as a favourable prognostic indicator, and may indicate a protective role for this antibody which should be followed up and possibly utilized in the treatment or in the design of a vaccine against HIV-1.", "contents": "Antibodies to reverse transcriptase in HIV infection and progression to AIDS. Serum antibodies to the reverse transcriptase (ART) of human immunodeficiency virus 1 (HIV-1) were sequentially determined by ELISA in a group of 41 HIV-seropositive male homosexuals and 101 matched healthy controls, over 1.5-6 years (mean follow-up 3.25 years). Mean ART levels were significantly higher in the patient group as compared to the controls (195 +/- 75 vs. 75 +/- 45 absorbance (A) units; P less than 0.05). When analyzed in parallel with clinical evaluation and T-cell subset determinations, a \"surge\" in ART activity was associated with a more favourable course: eleven patients whose ART profile showed an increase greater than 100 A units (mean delta A 159.6 units) showed an attenuated decrease of CD4+ (T helper) lymphocytes with a mean time of 42.5 months to reach a CD4+ number of 400 cells/mm3. In contrast, 25 matched seropositive patients whose ART remained constant became CD4+ less than 400 cells/mm3 within a mean time of 10.8 months (P less than 0.05). These results as well as individual patients' data support a surge in serum ART as a favourable prognostic indicator, and may indicate a protective role for this antibody which should be followed up and possibly utilized in the treatment or in the design of a vaccine against HIV-1."} {"id": "PMID:1280250", "title": "Efficient solid phase synthesis of mixed Thr(P)-, Ser(P)- and Tyr(P)-containing phosphopeptides by \"global\" \"phosphite-triester\" phosphorylation.", "content": "The synthesis of the mixed Thr(P)/Tyr(P)-containing peptide, Ala-Thr(P)-Tyr(P)-Ser-Ala, was accomplished by \"phosphite-triester\" phosphorylation of the resin-bound Thr/Tyr-containing peptide using di-t-butyl N,N-diethylphosphoramidite as the phosphitylation reagent. The pentapeptide-resin was assembled by Fmoc/solid-phase peptide synthesis with the use of PyBOP as coupling reagent and the hydroxy-amino acids incorporated as side-chain free Fmoc-Tyr-OH and Fmoc-Thr-OH. \"Global\" bis-phosphorylation of the peptide-resin was accomplished by treatment with di-t-butyl N,N-diethylphosphoramidite/1H-tetrazole followed by m-chloroperoxybenzoic acid oxidation of the intermediate di-t-butylphosphite triester. Simultaneous peptide-resin cleavage and peptide deprotection was effected by treatment of the peptide-resin with 5% anisole/TFA and gave the Thr(P)/Tyr(P)-containing phosphopeptide in high yield and purity. In addition, the tyrosyl residue was found to be phosphitylated in preference to the threonyl residue since the phosphitylation of the pentapeptide-resin using only 1.1 equiv. of di-t-butyl N,N-diethylphosphoramidite gave Ala-Thr-Tyr(P)-Ser-Ala as the major product and both Ala-Thr(P)-Tyr(P)-Ser-Ala and Ala-Thr-Tyr-Ser-Ala as minor products.", "contents": "Efficient solid phase synthesis of mixed Thr(P)-, Ser(P)- and Tyr(P)-containing phosphopeptides by \"global\" \"phosphite-triester\" phosphorylation. The synthesis of the mixed Thr(P)/Tyr(P)-containing peptide, Ala-Thr(P)-Tyr(P)-Ser-Ala, was accomplished by \"phosphite-triester\" phosphorylation of the resin-bound Thr/Tyr-containing peptide using di-t-butyl N,N-diethylphosphoramidite as the phosphitylation reagent. The pentapeptide-resin was assembled by Fmoc/solid-phase peptide synthesis with the use of PyBOP as coupling reagent and the hydroxy-amino acids incorporated as side-chain free Fmoc-Tyr-OH and Fmoc-Thr-OH. \"Global\" bis-phosphorylation of the peptide-resin was accomplished by treatment with di-t-butyl N,N-diethylphosphoramidite/1H-tetrazole followed by m-chloroperoxybenzoic acid oxidation of the intermediate di-t-butylphosphite triester. Simultaneous peptide-resin cleavage and peptide deprotection was effected by treatment of the peptide-resin with 5% anisole/TFA and gave the Thr(P)/Tyr(P)-containing phosphopeptide in high yield and purity. In addition, the tyrosyl residue was found to be phosphitylated in preference to the threonyl residue since the phosphitylation of the pentapeptide-resin using only 1.1 equiv. of di-t-butyl N,N-diethylphosphoramidite gave Ala-Thr-Tyr(P)-Ser-Ala as the major product and both Ala-Thr(P)-Tyr(P)-Ser-Ala and Ala-Thr-Tyr-Ser-Ala as minor products."} {"id": "PMID:1280251", "title": "Resolution of proline acylation problem for thiol capture strategy by use of a chloro-dibenzofuran template.", "content": "The acyl transfer rate for proline, in the prior thiol capture strategy, was enhanced by changing the electronic character of the dibenzofuran template. The rate of amide bond formation between proline and cysteine by the 1-chloro-4-hydroxy-6-mercaptodibenzofuran was measured to be 0.012 min-1, which translates to a half-life of 53 min. Further enhancement of the reaction rate was accomplished by the use of a 1,3-dichloro-dibenzofuran template. The k1 for the reaction was measured to be 0.093 min-1, and the half-life was calculated to be 7 min. To test the applicability of the activated template, 1-chloro-4-hydroxy-6-mercaptodibenzofuran, in peptide synthesis, the 34 amino acid long peptide, H-RPDFCLEPPYTGPCRKARNNFKSADECMRTCGGA-OH, was synthesized. This peptide represents the condensation of the N-terminal 13-mer and the C-terminal 21-mer of the basic pancreatic trypsin inhibitor.", "contents": "Resolution of proline acylation problem for thiol capture strategy by use of a chloro-dibenzofuran template. The acyl transfer rate for proline, in the prior thiol capture strategy, was enhanced by changing the electronic character of the dibenzofuran template. The rate of amide bond formation between proline and cysteine by the 1-chloro-4-hydroxy-6-mercaptodibenzofuran was measured to be 0.012 min-1, which translates to a half-life of 53 min. Further enhancement of the reaction rate was accomplished by the use of a 1,3-dichloro-dibenzofuran template. The k1 for the reaction was measured to be 0.093 min-1, and the half-life was calculated to be 7 min. To test the applicability of the activated template, 1-chloro-4-hydroxy-6-mercaptodibenzofuran, in peptide synthesis, the 34 amino acid long peptide, H-RPDFCLEPPYTGPCRKARNNFKSADECMRTCGGA-OH, was synthesized. This peptide represents the condensation of the N-terminal 13-mer and the C-terminal 21-mer of the basic pancreatic trypsin inhibitor."} {"id": "PMID:1280252", "title": "Alteration in myelin-associated proteins following spinal cord irradiation in guinea pigs.", "content": "The aim of this study was to investigate the pathological and cellular basis for radiation-induced myelopathy in guinea pigs by monitoring biochemical alterations in levels of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Guinea pigs were irradiated to the lumbar region with various doses of neutrons or cobalt gamma irradiation. The ED50s for paralysis were 17.2 Gy and 67.5 Gy for neutron and cobalt irradiation, respectively, and was histologically associated with demyelination. In spinal cords taken from animals at the onset of paralysis myelin basic protein levels were decreased in direct relationship to the radiation dose. The lowest doses to cause paralysis led to a 25% decrease in MBP levels. In a separate experiment, alterations in MBP were measured in the spinal cords over the time period leading up to paralysis. Surprisingly, decreases in MBP were found immediately after the end of the 4 week irradiation period. These early changes in MBP were not markedly dose dependent and occurred with nonparalyzing doses. Dose-dependent decreases were found only just before the onset of paralysis. CNPase activity measured in the same specimens showed changes that were essentially similar to those for MBP. In the CSF, MBP levels were essentially constant until onset of paralysis. This study showed that demyelination, as assessed by the levels of the myelin-associated proteins MBP and CNPase, can occur soon after spinal cord irradiation but that profound dose-dependent changes are seen only immediately preceding the onset of paralysis. Although increases in MBP in the CSF were associated with the onset of radiation-induced myelopathy, its assay is unlikely to predict this complication of irradiation.", "contents": "Alteration in myelin-associated proteins following spinal cord irradiation in guinea pigs. The aim of this study was to investigate the pathological and cellular basis for radiation-induced myelopathy in guinea pigs by monitoring biochemical alterations in levels of myelin basic protein and 2',3'-cyclic nucleotide phosphohydrolase. Guinea pigs were irradiated to the lumbar region with various doses of neutrons or cobalt gamma irradiation. The ED50s for paralysis were 17.2 Gy and 67.5 Gy for neutron and cobalt irradiation, respectively, and was histologically associated with demyelination. In spinal cords taken from animals at the onset of paralysis myelin basic protein levels were decreased in direct relationship to the radiation dose. The lowest doses to cause paralysis led to a 25% decrease in MBP levels. In a separate experiment, alterations in MBP were measured in the spinal cords over the time period leading up to paralysis. Surprisingly, decreases in MBP were found immediately after the end of the 4 week irradiation period. These early changes in MBP were not markedly dose dependent and occurred with nonparalyzing doses. Dose-dependent decreases were found only just before the onset of paralysis. CNPase activity measured in the same specimens showed changes that were essentially similar to those for MBP. In the CSF, MBP levels were essentially constant until onset of paralysis. This study showed that demyelination, as assessed by the levels of the myelin-associated proteins MBP and CNPase, can occur soon after spinal cord irradiation but that profound dose-dependent changes are seen only immediately preceding the onset of paralysis. Although increases in MBP in the CSF were associated with the onset of radiation-induced myelopathy, its assay is unlikely to predict this complication of irradiation."} {"id": "PMID:1280253", "title": "Globicatella sanguis gen.nov., sp.nov., a new gram-positive catalase-negative bacterium from human sources.", "content": "Phylogenetic studies were performed on some Gram-positive catalase-negative cocci from human clinical sources of uncertain taxonomic position. 16S rRNA sequence analysis demonstrated that the isolates represent a hitherto unknown line of descent within the low G+C Gram-positive bacteria for which the name Globicatella sanguis gen.nov., sp.nov. is proposed.", "contents": "Globicatella sanguis gen.nov., sp.nov., a new gram-positive catalase-negative bacterium from human sources. Phylogenetic studies were performed on some Gram-positive catalase-negative cocci from human clinical sources of uncertain taxonomic position. 16S rRNA sequence analysis demonstrated that the isolates represent a hitherto unknown line of descent within the low G+C Gram-positive bacteria for which the name Globicatella sanguis gen.nov., sp.nov. is proposed."} {"id": "PMID:1280254", "title": "Changes in human muscle protein synthesis after resistance exercise.", "content": "The purpose of this study was to investigate the magnitude and time course for changes in muscle protein synthesis (MPS) after a single bout of resistance exercise. Two groups of six male subjects performed heavy resistance exercise with the elbow flexors of one arm while the opposite arm served as a control. MPS from exercised (ex) and control (con) biceps brachii was assessed 4 (group A) and 24 h (group B) postexercise by the increment in L-[1-13C]leucine incorporation into muscle biopsy samples. In addition, RNA capacity and RNA activity were determined to assess whether transcriptional and/or translational processes affected MPS. MPS was significantly elevated in biceps of the ex compared with the con arms of both groups (group A, ex 0.1007 +/- 0.0330 vs. con 0.067 +/- 0.0204%/h; group B ex 0.0944 +/- 0.0363 vs. con 0.0452 +/- 0.0126%/h). RNA capacity was unchanged in the ex biceps of both groups relative to the con biceps, whereas RNA activity was significantly elevated in the ex biceps of both groups (group A, ex 0.19 +/- 0.10 vs. con 0.12 +/- 0.05 micrograms protein.h-1.microgram-1 total RNA; group B, ex 0.18 +/- 0.06 vs. con 0.08 +/- 0.02 micrograms protein.h-1.microgram-1 total RNA). The results indicate that a single bout of heavy resistance exercise can increase biceps MPS for up to 24 h postexercise. In addition, these increases appear to be due to changes in posttranscriptional events.", "contents": "Changes in human muscle protein synthesis after resistance exercise. The purpose of this study was to investigate the magnitude and time course for changes in muscle protein synthesis (MPS) after a single bout of resistance exercise. Two groups of six male subjects performed heavy resistance exercise with the elbow flexors of one arm while the opposite arm served as a control. MPS from exercised (ex) and control (con) biceps brachii was assessed 4 (group A) and 24 h (group B) postexercise by the increment in L-[1-13C]leucine incorporation into muscle biopsy samples. In addition, RNA capacity and RNA activity were determined to assess whether transcriptional and/or translational processes affected MPS. MPS was significantly elevated in biceps of the ex compared with the con arms of both groups (group A, ex 0.1007 +/- 0.0330 vs. con 0.067 +/- 0.0204%/h; group B ex 0.0944 +/- 0.0363 vs. con 0.0452 +/- 0.0126%/h). RNA capacity was unchanged in the ex biceps of both groups relative to the con biceps, whereas RNA activity was significantly elevated in the ex biceps of both groups (group A, ex 0.19 +/- 0.10 vs. con 0.12 +/- 0.05 micrograms protein.h-1.microgram-1 total RNA; group B, ex 0.18 +/- 0.06 vs. con 0.08 +/- 0.02 micrograms protein.h-1.microgram-1 total RNA). The results indicate that a single bout of heavy resistance exercise can increase biceps MPS for up to 24 h postexercise. In addition, these increases appear to be due to changes in posttranscriptional events."} {"id": "PMID:1280255", "title": "Acetylation of O-specific lipopolysaccharides from Shigella flexneri 3a and 2a occurs in Escherichia coli K-12 carrying cloned S. flexneri 3a and 2a rfb genes.", "content": "Most of the Shigella flexneri O-specific serotypes result from O-acetyl and/or glucosyl groups added to a common O-repeating unit of the lipopolysaccharide (LPS) molecule. The genes involved in acetylation and/or glucosylation of S. flexneri LPS are physically located on lysogenic bacteriophages, whereas the rfb cluster contains the biosynthesis genes for the common O-repeating unit (D.A.R. Simmons and E. Romanowska, J. Med. Microbiol. 23:289-302, 1987). Using a cosmid cloning strategy, we have cloned the rfb regions from S. flexneri 3a and 2a. Escherichia coli K-12 containing plasmids pYS1-5 (derived from S. flexneri 3a) and pEY5 (derived from S. flexneri 2a) expressed O-specific LPS which reacted immunologically with S. flexneri polyvalent O antiserum. However, O-specific LPS expressed in E. coli K-12 also reacted with group 6 antiserum, indicating the presence of O-acetyl groups attached to one of the rhamnose components of the O-repeating unit. This was confirmed by measuring the amounts of acetate released from purified LPS samples and also by the chemical removal of O-acetyl groups, which abolished group 6 reactivity. The O-acetylation phenotype was absent in an E. coli strain with an sbcB-his-rfb chromosomal deletion and could be restored upon conjugation of F' 129, which carries sequences corresponding to a portion of the deleted region. Our data demonstrate that E. coli K-12 strains possess a novel locus which directs the O acetylation of LPS and is located in the sbcB-rfb region of the chromosomal map.", "contents": "Acetylation of O-specific lipopolysaccharides from Shigella flexneri 3a and 2a occurs in Escherichia coli K-12 carrying cloned S. flexneri 3a and 2a rfb genes. Most of the Shigella flexneri O-specific serotypes result from O-acetyl and/or glucosyl groups added to a common O-repeating unit of the lipopolysaccharide (LPS) molecule. The genes involved in acetylation and/or glucosylation of S. flexneri LPS are physically located on lysogenic bacteriophages, whereas the rfb cluster contains the biosynthesis genes for the common O-repeating unit (D.A.R. Simmons and E. Romanowska, J. Med. Microbiol. 23:289-302, 1987). Using a cosmid cloning strategy, we have cloned the rfb regions from S. flexneri 3a and 2a. Escherichia coli K-12 containing plasmids pYS1-5 (derived from S. flexneri 3a) and pEY5 (derived from S. flexneri 2a) expressed O-specific LPS which reacted immunologically with S. flexneri polyvalent O antiserum. However, O-specific LPS expressed in E. coli K-12 also reacted with group 6 antiserum, indicating the presence of O-acetyl groups attached to one of the rhamnose components of the O-repeating unit. This was confirmed by measuring the amounts of acetate released from purified LPS samples and also by the chemical removal of O-acetyl groups, which abolished group 6 reactivity. The O-acetylation phenotype was absent in an E. coli strain with an sbcB-his-rfb chromosomal deletion and could be restored upon conjugation of F' 129, which carries sequences corresponding to a portion of the deleted region. Our data demonstrate that E. coli K-12 strains possess a novel locus which directs the O acetylation of LPS and is located in the sbcB-rfb region of the chromosomal map."} {"id": "PMID:1280256", "title": "A mutant endonuclease IV of Escherichia coli loses the ability to repair lethal DNA damage induced by hydrogen peroxide but not that induced by methyl methanesulfonate.", "content": "A mutant allele of the Escherichia coli nfo gene encoding endonuclease IV, nfo-186, was cloned into plasmid pUC18. When introduced into an E. coli xthA nfo mutant, the gene product of nfo-186 complemented the hypersensitivity of the mutant to methyl methanesulfonate (MMS) but not to hydrogen peroxide (H2O2) and bleomycin. These results suggest that the mutant endonuclease IV has normal activity for repairing DNA damages induced by MMS but not those induced by H2O2 and bleomycin. A missense mutation in the cloned nfo-186 gene, in which the wild-type glycine 149 was replaced by aspartic acid, was detected by DNA sequencing. The wild-type and mutant endonuclease IV were purified to near homogeneity, and their apurinic (AP) endonuclease and 3'-phosphatase activities were determined. No difference was observed in the AP endonuclease activities of the wild-type and mutant proteins. However, 3'-phosphatase activity was dramatically reduced in the mutant protein. From these results, it is concluded that the endonuclease IV186 protein is specifically deficient in the ability to remove 3'-terminus-blocking damage, which is required for DNA repair synthesis, and it is possible that the lethal DNA damage by H2O2 is 3'-blocking damage and not AP-site damage.", "contents": "A mutant endonuclease IV of Escherichia coli loses the ability to repair lethal DNA damage induced by hydrogen peroxide but not that induced by methyl methanesulfonate. A mutant allele of the Escherichia coli nfo gene encoding endonuclease IV, nfo-186, was cloned into plasmid pUC18. When introduced into an E. coli xthA nfo mutant, the gene product of nfo-186 complemented the hypersensitivity of the mutant to methyl methanesulfonate (MMS) but not to hydrogen peroxide (H2O2) and bleomycin. These results suggest that the mutant endonuclease IV has normal activity for repairing DNA damages induced by MMS but not those induced by H2O2 and bleomycin. A missense mutation in the cloned nfo-186 gene, in which the wild-type glycine 149 was replaced by aspartic acid, was detected by DNA sequencing. The wild-type and mutant endonuclease IV were purified to near homogeneity, and their apurinic (AP) endonuclease and 3'-phosphatase activities were determined. No difference was observed in the AP endonuclease activities of the wild-type and mutant proteins. However, 3'-phosphatase activity was dramatically reduced in the mutant protein. From these results, it is concluded that the endonuclease IV186 protein is specifically deficient in the ability to remove 3'-terminus-blocking damage, which is required for DNA repair synthesis, and it is possible that the lethal DNA damage by H2O2 is 3'-blocking damage and not AP-site damage."} {"id": "PMID:1280257", "title": "Generation of superoxide by purified brain nitric oxide synthase.", "content": "Brain nitric oxide synthase (NOS), which utilizes NADPH and calcium/calmodulin as cofactors for metabolizing L-arginine to nitric oxide (NO) and L-citrulline, contains recognition sites for the flavins FAD and FMN. Using a spin-trapping technique combined with electron spin resonance spectroscopy, we report that brain NOS generates superoxide O2-. in a calcium/calmodulin-dependent manner. The \"specific inhibitors\" of NOS, NG-monomethyl L-arginine (L-NMMA), and NG-nitro-L-arginine methyl ester (L-NAME), have different effects on O2-. generation. For L-NMMA, O2-. production is unaffected, while for L-NAME, inhibition of this free radical is concentration-dependent.", "contents": "Generation of superoxide by purified brain nitric oxide synthase. Brain nitric oxide synthase (NOS), which utilizes NADPH and calcium/calmodulin as cofactors for metabolizing L-arginine to nitric oxide (NO) and L-citrulline, contains recognition sites for the flavins FAD and FMN. Using a spin-trapping technique combined with electron spin resonance spectroscopy, we report that brain NOS generates superoxide O2-. in a calcium/calmodulin-dependent manner. The \"specific inhibitors\" of NOS, NG-monomethyl L-arginine (L-NMMA), and NG-nitro-L-arginine methyl ester (L-NAME), have different effects on O2-. generation. For L-NMMA, O2-. production is unaffected, while for L-NAME, inhibition of this free radical is concentration-dependent."} {"id": "PMID:1280258", "title": "Reconstitution of lipoprotein(a) by infusion of human low density lipoprotein into transgenic mice expressing human apolipoprotein(a).", "content": "Lipoprotein(a) (Lp(a)) is an atherosclerosis-causing lipoprotein that circulates in human plasma as a complex of low density lipoprotein (LDL) and apolipoprotein(a) (apo(a)). It is not known whether apo(a) attaches to LDL within hepatocytes prior to secretion or in plasma subsequent to secretion. Here we describe the development of a line of mice expressing the human apo(a) transgene under the control of the murine transferrin promoter. The apo(a) was secreted into the plasma, but circulated free of lipoproteins. When human (h)-LDL was injected intravenously, the circulating apo(a) rapidly associated with the lipoproteins, as determined by nondenaturing gel electrophoresis. Human HDL and mouse LDL had no such effect. When h-VLDL was injected, there was a delayed association of apo(a) with the lipoprotein fraction which suggests that apo(a) preferentially associated with a metabolic product of VLDL. The complex of apo(a) with LDL formed both in vivo and in vitro was resistant to boiling in the presence of detergents and denaturants, but was resolved upon disulfide reduction. These studies suggest that apo(a) fails to associate with mouse lipoproteins due to structural differences between human and mouse LDL, and that Lp(a) formation can occur in plasma through the association of apo(a) with circulating LDL.", "contents": "Reconstitution of lipoprotein(a) by infusion of human low density lipoprotein into transgenic mice expressing human apolipoprotein(a). Lipoprotein(a) (Lp(a)) is an atherosclerosis-causing lipoprotein that circulates in human plasma as a complex of low density lipoprotein (LDL) and apolipoprotein(a) (apo(a)). It is not known whether apo(a) attaches to LDL within hepatocytes prior to secretion or in plasma subsequent to secretion. Here we describe the development of a line of mice expressing the human apo(a) transgene under the control of the murine transferrin promoter. The apo(a) was secreted into the plasma, but circulated free of lipoproteins. When human (h)-LDL was injected intravenously, the circulating apo(a) rapidly associated with the lipoproteins, as determined by nondenaturing gel electrophoresis. Human HDL and mouse LDL had no such effect. When h-VLDL was injected, there was a delayed association of apo(a) with the lipoprotein fraction which suggests that apo(a) preferentially associated with a metabolic product of VLDL. The complex of apo(a) with LDL formed both in vivo and in vitro was resistant to boiling in the presence of detergents and denaturants, but was resolved upon disulfide reduction. These studies suggest that apo(a) fails to associate with mouse lipoproteins due to structural differences between human and mouse LDL, and that Lp(a) formation can occur in plasma through the association of apo(a) with circulating LDL."} {"id": "PMID:1280259", "title": "Molybdate increases intracellular 3',5'-guanosine cyclic monophosphate and stabilizes vitamin D receptor association with tubulin-containing filaments.", "content": "With a recently developed method we detected rapid and sequential reorganization of vitamin D receptors (VDR), including their temporary association with fibers, and we showed that calcitriol induces cGMP accumulation around reorganizing VDRs. In this report we first identified the VDR-associated fibers as microtubules: they show immunoreactivity with tubulin antisera and were sensitive to tubulin-disruptive agents. Tubulin-disruptive agents also prevented calcitriol-induced alignment and intranuclear accumulation of VDR and cGMP, but did not prevent the initial cGMP accumulation in the cytoplasm. Then we studied the effect of molybdate on VDR reorganization and on cGMP accumulation. Sodium molybdate inhibits steroid receptor transformation into a DNA binding form through interaction with the steroid binding region of the receptor. The mechanism of molybdate effect on steroid receptors is not well understood and the interaction of molybdate with guanylate cyclase has not been investigated. We found in cells pretreated with molybdate that the addition of calcitriol resulted in a prolonged and accentuated association of VDR and cGMP with the microtubules. Furthermore, both immunocytology and radioimmunoassay demonstrated that molybdate is a highly potent inducer of guanylate cyclase. Neither calcitriol nor molybdate effect on guanylate cyclase were prevented by methylene blue pretreatment, suggesting that they activate particulate guanylate cyclase. Pretreatment of cells with dibutyryl-cGMP mimicked molybdate effect on VDR reorganization. The effect of molybdate on cGMP may participate in molybdate stabilization of steroid receptors. We suggest that rapid cGMP accumulation after steroid exposure plays a role in facilitation of intracellular transport of the steroid receptor through interaction with microtubules.", "contents": "Molybdate increases intracellular 3',5'-guanosine cyclic monophosphate and stabilizes vitamin D receptor association with tubulin-containing filaments. With a recently developed method we detected rapid and sequential reorganization of vitamin D receptors (VDR), including their temporary association with fibers, and we showed that calcitriol induces cGMP accumulation around reorganizing VDRs. In this report we first identified the VDR-associated fibers as microtubules: they show immunoreactivity with tubulin antisera and were sensitive to tubulin-disruptive agents. Tubulin-disruptive agents also prevented calcitriol-induced alignment and intranuclear accumulation of VDR and cGMP, but did not prevent the initial cGMP accumulation in the cytoplasm. Then we studied the effect of molybdate on VDR reorganization and on cGMP accumulation. Sodium molybdate inhibits steroid receptor transformation into a DNA binding form through interaction with the steroid binding region of the receptor. The mechanism of molybdate effect on steroid receptors is not well understood and the interaction of molybdate with guanylate cyclase has not been investigated. We found in cells pretreated with molybdate that the addition of calcitriol resulted in a prolonged and accentuated association of VDR and cGMP with the microtubules. Furthermore, both immunocytology and radioimmunoassay demonstrated that molybdate is a highly potent inducer of guanylate cyclase. Neither calcitriol nor molybdate effect on guanylate cyclase were prevented by methylene blue pretreatment, suggesting that they activate particulate guanylate cyclase. Pretreatment of cells with dibutyryl-cGMP mimicked molybdate effect on VDR reorganization. The effect of molybdate on cGMP may participate in molybdate stabilization of steroid receptors. We suggest that rapid cGMP accumulation after steroid exposure plays a role in facilitation of intracellular transport of the steroid receptor through interaction with microtubules."} {"id": "PMID:1280260", "title": "Cleavage of tRNA by Fe(II)-bleomycin.", "content": "We have investigated the action of the chemotherapeutic agent Fe(II)-bleomycin on yeast tRNA(Phe), an RNA of known three-dimensional structure. In the absence of Mg2+ ions, the RNA is cleaved preferentially at two major positions, A31 and G53, both of which are located at the terminal base pairs of hairpin loops, and coincide with the location of tight Mg2+ binding sites. A fragment of the tRNA (residues 47-76) containing the T stem-loop is also cleaved specifically at G53. Cleavage of both the intact tRNA and the tRNA fragment is abolished in the presence of physiological concentrations of Mg2+ (> 0.5 mM). Since Fe(II) is not displaced from bleomycin under these conditions, we infer that tight binding of Mg2+ to tRNA excludes productive interactions between Fe(II)-bleomycin and the RNA. These results also show that loss of cleavage is not due to Mg(2+)-dependent formation of tertiary interactions between the D and T loops. In contrast, cleavage of synthetic DNA analogs of the anticodon and T stem-loops is not detectably inhibited by Mg2+, even at concentrations as high as 50 mM. In addition, the site specificities observed in cleavage of RNA and DNA differ significantly. From these results, and from similar findings with other representative RNA molecules, we suggest that the cleavage of RNA by Fe(II)-bleomycin is unlikely to be important for its therapeutic action.", "contents": "Cleavage of tRNA by Fe(II)-bleomycin. We have investigated the action of the chemotherapeutic agent Fe(II)-bleomycin on yeast tRNA(Phe), an RNA of known three-dimensional structure. In the absence of Mg2+ ions, the RNA is cleaved preferentially at two major positions, A31 and G53, both of which are located at the terminal base pairs of hairpin loops, and coincide with the location of tight Mg2+ binding sites. A fragment of the tRNA (residues 47-76) containing the T stem-loop is also cleaved specifically at G53. Cleavage of both the intact tRNA and the tRNA fragment is abolished in the presence of physiological concentrations of Mg2+ (> 0.5 mM). Since Fe(II) is not displaced from bleomycin under these conditions, we infer that tight binding of Mg2+ to tRNA excludes productive interactions between Fe(II)-bleomycin and the RNA. These results also show that loss of cleavage is not due to Mg(2+)-dependent formation of tertiary interactions between the D and T loops. In contrast, cleavage of synthetic DNA analogs of the anticodon and T stem-loops is not detectably inhibited by Mg2+, even at concentrations as high as 50 mM. In addition, the site specificities observed in cleavage of RNA and DNA differ significantly. From these results, and from similar findings with other representative RNA molecules, we suggest that the cleavage of RNA by Fe(II)-bleomycin is unlikely to be important for its therapeutic action."} {"id": "PMID:1280261", "title": "Multiple trkA proteins in PC12 cells bind NGF with a slow association rate.", "content": "Rat pheochromocytoma (PC12) cells express two distinct nerve growth factor receptors (NGFRs), p75NGFR and trkA (p140trk). In addition to these receptors, by using 125I-mNGF affinity labeling and BS3 chemical cross-linking of PC12 cell protein, we have identified two additional trkA protein bands with apparent molecular weights of 220,000 and 300,000. These bands contain trkA, but were not immunoprecipitated by p75NGFR-specific antisera, suggesting that they do not represent trkA/p75NGFR protein complexes. The 220-kDa trkA band apparently represents trkA with alternate post-translational modification. The appearance of the 300-kDa trkA band was dependent on cross-linker concentration and could be diminished in the presence of reducing agents, suggesting that it represents a trkA dimer. All trkA bands were phosphorylated on tyrosine residues when bound to mNGF, suggesting that they participate in NGF-induced signal transduction. NGF binding kinetics to all three trkA bands were indistinguishable, with slow dissociation rates, and a slow association rate that required approximately 1 h to reach equilibrium levels at 4 degrees C. All three trkA bands bound the related neurotrophin brain-derived neurotrophic factor and neurotrophin-3 with a profile characteristic of trkA.", "contents": "Multiple trkA proteins in PC12 cells bind NGF with a slow association rate. Rat pheochromocytoma (PC12) cells express two distinct nerve growth factor receptors (NGFRs), p75NGFR and trkA (p140trk). In addition to these receptors, by using 125I-mNGF affinity labeling and BS3 chemical cross-linking of PC12 cell protein, we have identified two additional trkA protein bands with apparent molecular weights of 220,000 and 300,000. These bands contain trkA, but were not immunoprecipitated by p75NGFR-specific antisera, suggesting that they do not represent trkA/p75NGFR protein complexes. The 220-kDa trkA band apparently represents trkA with alternate post-translational modification. The appearance of the 300-kDa trkA band was dependent on cross-linker concentration and could be diminished in the presence of reducing agents, suggesting that it represents a trkA dimer. All trkA bands were phosphorylated on tyrosine residues when bound to mNGF, suggesting that they participate in NGF-induced signal transduction. NGF binding kinetics to all three trkA bands were indistinguishable, with slow dissociation rates, and a slow association rate that required approximately 1 h to reach equilibrium levels at 4 degrees C. All three trkA bands bound the related neurotrophin brain-derived neurotrophic factor and neurotrophin-3 with a profile characteristic of trkA."} {"id": "PMID:1280262", "title": "Acidic fibroblast growth factor autocrine system as a mediator of calcium-regulated parathyroid cell growth.", "content": "Both parathyroid hormone secretion and cell growth are negatively regulated by extracellular calcium in parathyroid cells. The mechanism of growth regulation by calcium has been unknown. Previously, we reported that clonal parathyroid cells (PT-r cells) bear two high affinity receptors for acidic fibroblast growth factor (aFGF) and that at least a subpopulation of the receptors with a higher molecular mass carries heparan sulfate (HS) glycosaminoglycan chains which give the receptor higher affinity (Sakaguchi, K., Yanagishita, M., Takeuchi, Y., and Aurbach, G. D. (1991) J. Biol. Chem. 266, 7270-7278). Here, I have found that the parathyroid cells expressed aFGF and that aFGF receptors with lower affinity apparently translocated in response to changing extracellular calcium concentrations. Expression of both aFGF mRNA and peptide was suppressed by calcium. Cells had more ligand-accessible receptors on the cell surface at lower calcium concentrations. This apparent translocation was temperature-dependent but independent of de novo protein synthesis. Heparin or HS glycosaminoglycans are a prerequisite for the FGF receptor encoded by flg gene to bind basic FGF (Yayon, A., Klagsbrun, M., Esko, J. D., Leder, P., and Ornitz, D. M. (1991) Cell 64, 841-848). In PT-r cells, major cellular HS proteoglycans redistribute between intracellular and extracellular compartments with more HS proteoglycans expressed on the cell surface at lower calcium concentrations (Takeuchi, Y., Sakaguchi, K., Yanagishita, M., Aurbach, G. D., and Hascall, V. C. (1990) J. Biol. Chem. 265, 13661-13668). However, this redistribution of HS proteoglycans cannot explain the difference in bindability of radiolabeled aFGF to its receptors in different calcium concentrations, since addition of heparin did not change the binding of radiolabeled aFGF to the receptors either at high or low calcium conditions. In concordance with the apparent translocation of aFGF receptors, thymidine incorporation was stimulated by decreasing extracellular calcium concentrations with further stimulation by added aFGF. Anti-aFGF antibody inhibited thymidine incorporation by more than 32% in the cells exposed to 0.05 mM Ca2+ shortly before adding [3H]thymidine, whereas the incorporation was not significantly affected by the antibody at 0.7 mM Ca2+. Cell growth was also stimulated by low calcium. Anti-aFGF antibody inhibited cell growth significantly only at low calcium concentrations. From these observations, an aFGF autocrine system including the apparent translocation of aFGF receptors may explain, if not entirely, the mechanism by which calcium regulates parathyroid cell growth.", "contents": "Acidic fibroblast growth factor autocrine system as a mediator of calcium-regulated parathyroid cell growth. Both parathyroid hormone secretion and cell growth are negatively regulated by extracellular calcium in parathyroid cells. The mechanism of growth regulation by calcium has been unknown. Previously, we reported that clonal parathyroid cells (PT-r cells) bear two high affinity receptors for acidic fibroblast growth factor (aFGF) and that at least a subpopulation of the receptors with a higher molecular mass carries heparan sulfate (HS) glycosaminoglycan chains which give the receptor higher affinity (Sakaguchi, K., Yanagishita, M., Takeuchi, Y., and Aurbach, G. D. (1991) J. Biol. Chem. 266, 7270-7278). Here, I have found that the parathyroid cells expressed aFGF and that aFGF receptors with lower affinity apparently translocated in response to changing extracellular calcium concentrations. Expression of both aFGF mRNA and peptide was suppressed by calcium. Cells had more ligand-accessible receptors on the cell surface at lower calcium concentrations. This apparent translocation was temperature-dependent but independent of de novo protein synthesis. Heparin or HS glycosaminoglycans are a prerequisite for the FGF receptor encoded by flg gene to bind basic FGF (Yayon, A., Klagsbrun, M., Esko, J. D., Leder, P., and Ornitz, D. M. (1991) Cell 64, 841-848). In PT-r cells, major cellular HS proteoglycans redistribute between intracellular and extracellular compartments with more HS proteoglycans expressed on the cell surface at lower calcium concentrations (Takeuchi, Y., Sakaguchi, K., Yanagishita, M., Aurbach, G. D., and Hascall, V. C. (1990) J. Biol. Chem. 265, 13661-13668). However, this redistribution of HS proteoglycans cannot explain the difference in bindability of radiolabeled aFGF to its receptors in different calcium concentrations, since addition of heparin did not change the binding of radiolabeled aFGF to the receptors either at high or low calcium conditions. In concordance with the apparent translocation of aFGF receptors, thymidine incorporation was stimulated by decreasing extracellular calcium concentrations with further stimulation by added aFGF. Anti-aFGF antibody inhibited thymidine incorporation by more than 32% in the cells exposed to 0.05 mM Ca2+ shortly before adding [3H]thymidine, whereas the incorporation was not significantly affected by the antibody at 0.7 mM Ca2+. Cell growth was also stimulated by low calcium. Anti-aFGF antibody inhibited cell growth significantly only at low calcium concentrations. From these observations, an aFGF autocrine system including the apparent translocation of aFGF receptors may explain, if not entirely, the mechanism by which calcium regulates parathyroid cell growth."} {"id": "PMID:1280263", "title": "Actinomycin prevents the destabilization of neurofilament mRNA in primary sensory neurons.", "content": "The levels of light, mid-sized, and heavy neurofilament (NF) mRNAs were compared to that of beta-actin mRNA in primary dissociated cultures of adult rat dorsal root ganglia (DRG). Decreases in the levels of all three NF mRNAs occur after 24 h in culture, mimicking the down-regulation of NF mRNAs in axotomized DRG neurons. The loss of NF mRNAs in DRG cultures is prevented by actinomycin and, to a lesser extent, by cycloheximide. Based on decay curves in actinomycin-treated cultures, the half-lives of NF mRNAs are at least 4 days in DRG neurons, but < 24 h in PC12 cells. Our data support the view that NF mRNAs are stabilized in DRG neurons and that stabilization prevents destabilization by a transcription-dependent process. We further propose that putative stabilizing factor(s) are able to prevent degradation of NF transcripts in intact neurons, but not in axotomized or cultured neurons.", "contents": "Actinomycin prevents the destabilization of neurofilament mRNA in primary sensory neurons. The levels of light, mid-sized, and heavy neurofilament (NF) mRNAs were compared to that of beta-actin mRNA in primary dissociated cultures of adult rat dorsal root ganglia (DRG). Decreases in the levels of all three NF mRNAs occur after 24 h in culture, mimicking the down-regulation of NF mRNAs in axotomized DRG neurons. The loss of NF mRNAs in DRG cultures is prevented by actinomycin and, to a lesser extent, by cycloheximide. Based on decay curves in actinomycin-treated cultures, the half-lives of NF mRNAs are at least 4 days in DRG neurons, but < 24 h in PC12 cells. Our data support the view that NF mRNAs are stabilized in DRG neurons and that stabilization prevents destabilization by a transcription-dependent process. We further propose that putative stabilizing factor(s) are able to prevent degradation of NF transcripts in intact neurons, but not in axotomized or cultured neurons."} {"id": "PMID:1280264", "title": "Endothelins secreted from human keratinocytes are intrinsic mitogens for human melanocytes.", "content": "We recently demonstrated that human melanocyte proliferation and differentiation could be stimulated by endothelin (ET) derivatives via a receptor-mediated signal transduction pathway (Yada, Y., Higuchi, K., and Imokawa, G. (1991) J. Biol. Chem. 266, 18352-18357). We show here that the growth factors for human melanocytes are produced and secreted by the surrounding cells, namely human keratinocytes for ET-1 and Big-ET-1. Northern blots have revealed the presence of ET-1 gene transcripts in proliferating human keratinocytes. The ET-1 production by human keratinocytes increased after irradiation with ultraviolet B (UVB) in a dose-dependent manner, accompanied by the significant secretion of interleukin 1 alpha (IL-1 alpha). Among the cytokines related to UVB-induced cellular reactions and keratinocyte growth, only IL-1 alpha and -1 beta stimulated the secretion of ET-1 and Big-ET-1 but not of ET-3 and Big-ET-3 in a time-dependent manner. Northern blots for IL-1 alpha-stimulated or UVB-exposed human keratinocytes revealed that production of ET-1 gene transcripts markedly increased (by about 300 or 1,200%) with constant levels of beta-actin gene transcripts. In a parallel study, the medium conditioned by UVB-exposed human keratinocytes elicited a significant anti-ET-1 antibody-suppressible increase in DNA synthesis by cultured human melanocytes in a UV dose-dependent manner, which was associated with a marked and rapid (80 s) increase in the intracellular calcium level upon incubation with human melanocytes. These studies suggest that ETs produced and secreted by keratinocytes play an essential role in the maintenance of melanocyte proliferation and UV hyperpigmentation in the epidermis.", "contents": "Endothelins secreted from human keratinocytes are intrinsic mitogens for human melanocytes. We recently demonstrated that human melanocyte proliferation and differentiation could be stimulated by endothelin (ET) derivatives via a receptor-mediated signal transduction pathway (Yada, Y., Higuchi, K., and Imokawa, G. (1991) J. Biol. Chem. 266, 18352-18357). We show here that the growth factors for human melanocytes are produced and secreted by the surrounding cells, namely human keratinocytes for ET-1 and Big-ET-1. Northern blots have revealed the presence of ET-1 gene transcripts in proliferating human keratinocytes. The ET-1 production by human keratinocytes increased after irradiation with ultraviolet B (UVB) in a dose-dependent manner, accompanied by the significant secretion of interleukin 1 alpha (IL-1 alpha). Among the cytokines related to UVB-induced cellular reactions and keratinocyte growth, only IL-1 alpha and -1 beta stimulated the secretion of ET-1 and Big-ET-1 but not of ET-3 and Big-ET-3 in a time-dependent manner. Northern blots for IL-1 alpha-stimulated or UVB-exposed human keratinocytes revealed that production of ET-1 gene transcripts markedly increased (by about 300 or 1,200%) with constant levels of beta-actin gene transcripts. In a parallel study, the medium conditioned by UVB-exposed human keratinocytes elicited a significant anti-ET-1 antibody-suppressible increase in DNA synthesis by cultured human melanocytes in a UV dose-dependent manner, which was associated with a marked and rapid (80 s) increase in the intracellular calcium level upon incubation with human melanocytes. These studies suggest that ETs produced and secreted by keratinocytes play an essential role in the maintenance of melanocyte proliferation and UV hyperpigmentation in the epidermis."} {"id": "PMID:1280265", "title": "Comparison of Moloney murine leukemia virus mutation rate with the fidelity of its reverse transcriptase in vitro.", "content": "The role of Moloney murine leukemia virus (MoMLV) reverse transcriptase (RT) in the generation of base substitution mutations during retroviral replication was analyzed. To that effect, the in vitro fidelity of the MoMLV RT was compared to the rate of base substitution mutations occurring during the replication of an MoMLV-based retroviral vector. Using the vector in an amber reversion assay, the base substitution mutation rate at a single locus was found to be 2 x 10(-6)/base pair in one cycle of vector virus replication. Analysis of the fidelity of the purified RT using the same template sequence revealed that, of the two mispairs (A.C and T.G) that would lead to reversion of the amber codon during replication, A.C occurs at a rate of 4.0 x 10(-6), and T.G occurs at a rate of 0.7 x 10(-4). While the rate of formation of A.C is very similar to the vector mutation rate, the rate of formation of T.G is more than 30 times higher. This discrepancy in rates suggests that there are other elements in the infected cells that contribute to the fidelity of viral replication.", "contents": "Comparison of Moloney murine leukemia virus mutation rate with the fidelity of its reverse transcriptase in vitro. The role of Moloney murine leukemia virus (MoMLV) reverse transcriptase (RT) in the generation of base substitution mutations during retroviral replication was analyzed. To that effect, the in vitro fidelity of the MoMLV RT was compared to the rate of base substitution mutations occurring during the replication of an MoMLV-based retroviral vector. Using the vector in an amber reversion assay, the base substitution mutation rate at a single locus was found to be 2 x 10(-6)/base pair in one cycle of vector virus replication. Analysis of the fidelity of the purified RT using the same template sequence revealed that, of the two mispairs (A.C and T.G) that would lead to reversion of the amber codon during replication, A.C occurs at a rate of 4.0 x 10(-6), and T.G occurs at a rate of 0.7 x 10(-4). While the rate of formation of A.C is very similar to the vector mutation rate, the rate of formation of T.G is more than 30 times higher. This discrepancy in rates suggests that there are other elements in the infected cells that contribute to the fidelity of viral replication."} {"id": "PMID:1280266", "title": "The inclusion of the type III repeat ED-B in the fibronectin molecule generates conformational modifications that unmask a cryptic sequence.", "content": "We have previously reported an anti-fibronectin monoclonal antibody (mAb) (BC-1) which reacts with an ED-B-containing beta-galactosidase-fibronectin fusion protein but not with an identical beta-galactosidase-fibronectin fusion protein in which the ED-B sequence is omitted. In further experiments aimed at localizing more precisely the epitope recognized by this mAb, we demonstrate that 1) the mAb BC-1 is indeed specific for ED-B-containing fibronectin (FN) molecules even though the epitope recognized by this mAb is localized on the type III homology repeat 7 (the one which precedes the ED-B sequence) and 2) in fibronectin molecules lacking the ED-B sequence, this epitope is masked. We further demonstrate that, to mask the epitope recognized by the mAb BC-1, the presence of at least half of the FN type III homology repeat 9 is necessary. We also report the production of the mAb IST-6 which recognizes only FN molecules in which the ED-B sequence is lacking. These data clearly demonstrate that the presence of the ED-B sequence within FN molecules generates conformational modification in the central part of the molecules that unmasks previously cryptic sequences and masks others.", "contents": "The inclusion of the type III repeat ED-B in the fibronectin molecule generates conformational modifications that unmask a cryptic sequence. We have previously reported an anti-fibronectin monoclonal antibody (mAb) (BC-1) which reacts with an ED-B-containing beta-galactosidase-fibronectin fusion protein but not with an identical beta-galactosidase-fibronectin fusion protein in which the ED-B sequence is omitted. In further experiments aimed at localizing more precisely the epitope recognized by this mAb, we demonstrate that 1) the mAb BC-1 is indeed specific for ED-B-containing fibronectin (FN) molecules even though the epitope recognized by this mAb is localized on the type III homology repeat 7 (the one which precedes the ED-B sequence) and 2) in fibronectin molecules lacking the ED-B sequence, this epitope is masked. We further demonstrate that, to mask the epitope recognized by the mAb BC-1, the presence of at least half of the FN type III homology repeat 9 is necessary. We also report the production of the mAb IST-6 which recognizes only FN molecules in which the ED-B sequence is lacking. These data clearly demonstrate that the presence of the ED-B sequence within FN molecules generates conformational modification in the central part of the molecules that unmasks previously cryptic sequences and masks others."} {"id": "PMID:1280267", "title": "Isolation and characterization of a pepsin C zymogen produced by human breast tissues.", "content": "An aspartic proteinase present in cyst fluid from women with gross cystic breast disease was purified by a procedure involving affinity chromatography on pepstatin-agarose and size-exclusion high performance liquid chromatography. The amino-terminal sequence of the purified breast proteinase was identical to that corresponding to gastric pepsinogen C. Additional data on cleavage specificity, pH optimum, and immunological properties supported the close relationship between both molecules. Northern blot analysis and polymerase chain reaction amplification studies performed on RNAs obtained from normal and pathological breast tissues demonstrated that the protein is produced by mammary carcinomas and cysts, but not by the normal resting mammary gland. Immunohistochemical staining of paraffin-embedded tissue sections confirmed the existence of a subset of tumors that have the ability to synthesize and secrete this pepsin zymogen. On the basis of these results, we suggest that pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases, being also of potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies.", "contents": "Isolation and characterization of a pepsin C zymogen produced by human breast tissues. An aspartic proteinase present in cyst fluid from women with gross cystic breast disease was purified by a procedure involving affinity chromatography on pepstatin-agarose and size-exclusion high performance liquid chromatography. The amino-terminal sequence of the purified breast proteinase was identical to that corresponding to gastric pepsinogen C. Additional data on cleavage specificity, pH optimum, and immunological properties supported the close relationship between both molecules. Northern blot analysis and polymerase chain reaction amplification studies performed on RNAs obtained from normal and pathological breast tissues demonstrated that the protein is produced by mammary carcinomas and cysts, but not by the normal resting mammary gland. Immunohistochemical staining of paraffin-embedded tissue sections confirmed the existence of a subset of tumors that have the ability to synthesize and secrete this pepsin zymogen. On the basis of these results, we suggest that pepsinogen C expression by human mammary epithelium may be involved in the development of breast diseases, being also of potential interest as a biochemical marker of the hormonal imbalance underlying these pathologies."} {"id": "PMID:1280268", "title": "UV light stress induces the synthesis of the early light-inducible protein and prevents its degradation.", "content": "ELIP is a nuclear-encoded protein localized in the thylakoid membranes. The protein is specifically induced by blue light in mature, light-grown plants (Adamska, I., Ohad, I., and Kloppstech, K. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 2610-2613), as well as in plants developed in the light in which pigment synthesis and plastid development were inhibited by the bleaching herbicide norflurazon. ELIP transcription and protein accumulation are induced also by UVA but not by UVB light. However, UVB light allows ELIP synthesis induced by superimposed white light. The protein is stable under light stress including UVA and UVB light, but it is rapidly degraded upon cessation of the light stress conditions. ELIP synthesis and integration into the chloroplast membranes is related neither to chloroplast translation activity nor to photosynthetic electron flow. Inhibition of carotenoid synthesis by fluridone, a bleaching herbicide which causes extensive damage to the photosynthetic apparatus, does not affect induction of ELIP transcription during light stress but greatly enhances ELIP accumulation. Based on these results it is proposed that ELIP turnover is related to the light stress and recovery process in plants.", "contents": "UV light stress induces the synthesis of the early light-inducible protein and prevents its degradation. ELIP is a nuclear-encoded protein localized in the thylakoid membranes. The protein is specifically induced by blue light in mature, light-grown plants (Adamska, I., Ohad, I., and Kloppstech, K. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 2610-2613), as well as in plants developed in the light in which pigment synthesis and plastid development were inhibited by the bleaching herbicide norflurazon. ELIP transcription and protein accumulation are induced also by UVA but not by UVB light. However, UVB light allows ELIP synthesis induced by superimposed white light. The protein is stable under light stress including UVA and UVB light, but it is rapidly degraded upon cessation of the light stress conditions. ELIP synthesis and integration into the chloroplast membranes is related neither to chloroplast translation activity nor to photosynthetic electron flow. Inhibition of carotenoid synthesis by fluridone, a bleaching herbicide which causes extensive damage to the photosynthetic apparatus, does not affect induction of ELIP transcription during light stress but greatly enhances ELIP accumulation. Based on these results it is proposed that ELIP turnover is related to the light stress and recovery process in plants."} {"id": "PMID:1280269", "title": "Three-dimensional structure of the truncated core of the Saccharomyces cerevisiae pyruvate dehydrogenase complex determined from negative stain and cryoelectron microscopy images.", "content": "Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of the three functional classes of multienzyme complexes that catalyze the oxidative decarboxylation of alpha-keto acids, forms the central core to which the other components are attached. We have imaged by negative stain and cryoelectron microscopy the truncated dihydrolipoamide acetyltransferase core (60 subunits; M(r) = 2.7 x 10(6)) of the Saccharomyces cerevisiae pyruvate dehydrogenase complex. Using icosahedral particle reconstruction techniques, we determined its structure to 25 A resolution. Although the model derived from the negative stain reconstruction was approximately 20% smaller than the model derived from the frozen-hydrated data, when corrected for the effects of the electron microscope contrast transfer functions, the reconstructions showed excellent correspondence. The pentagonal dodecahedron-shaped macromolecule has a maximum diameter, as measured along the 3-fold axis, of approximately 226 A (frozen-hydrated value), and 12 large openings (approximately 63 A in diameter) on the 5-fold axes that lead into a large solvent-accessible cavity (approximately 76-140 A diameter). The 20 vertices consist of cone-shaped trimers, each with a flattened base on the outside of the structure and an apex directed toward the center. The trimers are interconnected by 20 A thick \"bridges\" on the 2-fold axes. These studies also show that the highest resolution features apparent in the frozen-hydrated reconstruction are revealed in a filtered reconstruction of the stained molecule.", "contents": "Three-dimensional structure of the truncated core of the Saccharomyces cerevisiae pyruvate dehydrogenase complex determined from negative stain and cryoelectron microscopy images. Dihydrolipoamide acyltransferase (E2), a catalytic and structural component of the three functional classes of multienzyme complexes that catalyze the oxidative decarboxylation of alpha-keto acids, forms the central core to which the other components are attached. We have imaged by negative stain and cryoelectron microscopy the truncated dihydrolipoamide acetyltransferase core (60 subunits; M(r) = 2.7 x 10(6)) of the Saccharomyces cerevisiae pyruvate dehydrogenase complex. Using icosahedral particle reconstruction techniques, we determined its structure to 25 A resolution. Although the model derived from the negative stain reconstruction was approximately 20% smaller than the model derived from the frozen-hydrated data, when corrected for the effects of the electron microscope contrast transfer functions, the reconstructions showed excellent correspondence. The pentagonal dodecahedron-shaped macromolecule has a maximum diameter, as measured along the 3-fold axis, of approximately 226 A (frozen-hydrated value), and 12 large openings (approximately 63 A in diameter) on the 5-fold axes that lead into a large solvent-accessible cavity (approximately 76-140 A diameter). The 20 vertices consist of cone-shaped trimers, each with a flattened base on the outside of the structure and an apex directed toward the center. The trimers are interconnected by 20 A thick \"bridges\" on the 2-fold axes. These studies also show that the highest resolution features apparent in the frozen-hydrated reconstruction are revealed in a filtered reconstruction of the stained molecule."} {"id": "PMID:1280270", "title": "Yolk vitronectin. Purification and differences from its blood homologue in molecular size, heparin binding, collagen binding, and bound carbohydrate.", "content": "This is the first report on a unique vitronectin molecule, yolk vitronectin, which is similar to its blood homologue in cell spreading activity but different in molecular size, bound carbohydrate, and heparin and collagen binding activity. Yolk vitronectin was purified 2,500-fold from chick egg yolk by a combination of hydroxylapatite, DEAE-cellulose, and anti-vitronectin-Sepharose column chromatographies. In SDS-polyacrylamide gel electrophoresis under reducing conditions, yolk vitronectin was separated into 54- and 45-kDa bands, which are 16 and 25 kDa smaller, respectively, than the 70-kDa major band of chick blood vitronectin. The 54-kDa band shares the same NH2-terminal sequence as chick blood vitronectin. In contrast, the NH2-terminal sequence of the 45-kDa band is somewhat homologous with the internal sequences of mammalian vitronectins beginning at the 50th amino acid from the NH2 terminus. The bound carbohydrate of the 54- and 45-kDa species of yolk vitronectin is similar to, but distinct from, that of blood vitronectin. Unlike blood vitronectin, yolk vitronectin cannot bind to either heparin or collagen.", "contents": "Yolk vitronectin. Purification and differences from its blood homologue in molecular size, heparin binding, collagen binding, and bound carbohydrate. This is the first report on a unique vitronectin molecule, yolk vitronectin, which is similar to its blood homologue in cell spreading activity but different in molecular size, bound carbohydrate, and heparin and collagen binding activity. Yolk vitronectin was purified 2,500-fold from chick egg yolk by a combination of hydroxylapatite, DEAE-cellulose, and anti-vitronectin-Sepharose column chromatographies. In SDS-polyacrylamide gel electrophoresis under reducing conditions, yolk vitronectin was separated into 54- and 45-kDa bands, which are 16 and 25 kDa smaller, respectively, than the 70-kDa major band of chick blood vitronectin. The 54-kDa band shares the same NH2-terminal sequence as chick blood vitronectin. In contrast, the NH2-terminal sequence of the 45-kDa band is somewhat homologous with the internal sequences of mammalian vitronectins beginning at the 50th amino acid from the NH2 terminus. The bound carbohydrate of the 54- and 45-kDa species of yolk vitronectin is similar to, but distinct from, that of blood vitronectin. Unlike blood vitronectin, yolk vitronectin cannot bind to either heparin or collagen."} {"id": "PMID:1280272", "title": "Activation of the alpha subunit of Gs in intact cells alters its abundance, rate of degradation, and membrane avidity.", "content": "Binding of GTP induces alpha subunits of heterotrimeric G proteins to take on an active conformation, capable of regulating effector molecules. We expressed epitope-tagged versions of the alpha subunit (alpha s) of Gs in genetically alpha s-deficient S49 cyc- cells. Addition of a hemagglutinin (HA) epitope did not alter the ability of wild type alpha s to mediate hormonal stimulation of adenylyl cyclase or to attach to cell membranes. The HA epitope did, however, allow a mAb to immunoprecipitate the recombinant protein (HA-alpha s) quantitatively from cell extracts. We activated the epitope-tagged alpha s in intact cells by: (a) exposure of cells to cholera toxin, which activates alpha s by covalent modification; (b) mutational replacement of arginine-201 in HA-alpha s by a cysteine residue, to create HA-alpha s-R201C; like the cholera toxin-catalyzed modification, this mutation activates alpha s by slowing its intrinsic GTPase activity; and (c) treatment of cells with the beta-adrenoceptor agonist, isoproterenol, which promotes binding of GTP to alpha s, thereby activating adenylyl cyclase. Both cholera toxin and the R201C mutation accelerated the rate of degradation of alpha s (0.03 h-1) by three- to fourfold and induced a partial shift of the protein from a membrane bound to a soluble compartment. At steady state, 80% of HA-alpha s- R201C was found in the soluble fraction, as compared to 10% of wild type HA-alpha s. Isoproterenol rapidly (in < 2 min) caused 20% of HA-alpha s to shift from the membrane-bound to the soluble compartment. Cholera toxin induced a 3.5-fold increase in the rate of degradation of a second mutant, HA-alpha s-G226A, but did not cause it to move into the soluble fraction; this observation shows that loss of membrane attachment is not responsible for the accelerated degradation of alpha s in response to activation. Taken together, these findings show that activation of alpha s induces a conformational change that loosens its attachment to membranes and increases its degradation rate.", "contents": "Activation of the alpha subunit of Gs in intact cells alters its abundance, rate of degradation, and membrane avidity. Binding of GTP induces alpha subunits of heterotrimeric G proteins to take on an active conformation, capable of regulating effector molecules. We expressed epitope-tagged versions of the alpha subunit (alpha s) of Gs in genetically alpha s-deficient S49 cyc- cells. Addition of a hemagglutinin (HA) epitope did not alter the ability of wild type alpha s to mediate hormonal stimulation of adenylyl cyclase or to attach to cell membranes. The HA epitope did, however, allow a mAb to immunoprecipitate the recombinant protein (HA-alpha s) quantitatively from cell extracts. We activated the epitope-tagged alpha s in intact cells by: (a) exposure of cells to cholera toxin, which activates alpha s by covalent modification; (b) mutational replacement of arginine-201 in HA-alpha s by a cysteine residue, to create HA-alpha s-R201C; like the cholera toxin-catalyzed modification, this mutation activates alpha s by slowing its intrinsic GTPase activity; and (c) treatment of cells with the beta-adrenoceptor agonist, isoproterenol, which promotes binding of GTP to alpha s, thereby activating adenylyl cyclase. Both cholera toxin and the R201C mutation accelerated the rate of degradation of alpha s (0.03 h-1) by three- to fourfold and induced a partial shift of the protein from a membrane bound to a soluble compartment. At steady state, 80% of HA-alpha s- R201C was found in the soluble fraction, as compared to 10% of wild type HA-alpha s. Isoproterenol rapidly (in < 2 min) caused 20% of HA-alpha s to shift from the membrane-bound to the soluble compartment. Cholera toxin induced a 3.5-fold increase in the rate of degradation of a second mutant, HA-alpha s-G226A, but did not cause it to move into the soluble fraction; this observation shows that loss of membrane attachment is not responsible for the accelerated degradation of alpha s in response to activation. Taken together, these findings show that activation of alpha s induces a conformational change that loosens its attachment to membranes and increases its degradation rate."} {"id": "PMID:1280271", "title": "Does iloprost mediate thromboxane activity and polymorphonuclear leukocyte sequestration in ischemic skeletal muscle?", "content": "Thromboxane is known to alter the endothelial cytoskeleton, thereby causing increased endothelial permeability and polymorphonuclear leukocyte (PMN) sequestration in the lungs. We investigated whether iloprost (a stable prostacyclin analog) can decrease thromboxane activity and consequently PMN sequestration because of its anti-platelet aggregation effect. This premise was investigated in a canine isolated gracilis muscle model using 18 animals. Six animals (group I) had the gracilis muscle subjected to 6 hours of complete ischemia followed by 48 hours of reperfusion. Group II (n = 6) received intravenous infusion of iloprost (0.45 micrograms/kg/hr) throughout the experiment (1 hour preischemia, 6 hours of ischemia and 1 hour of reperfusion) and boluses of 0.45 micrograms/kg 10 minutes before ischemia and reperfusion. Group III (n = 6) underwent a similar ischemic interval, but were given iloprost bolus of 0.45 micrograms/kg followed by intravenous infusion of 0.45 micrograms/kg/hr during 48 hours of reperfusion. Gracilis venous samples were obtained at preischemia (PI) and 1 hour of reperfusion (all 3 groups) and at 48 hours of reperfusion (groups I and III) to measure thromboxane (TXB2) levels. Muscle biopsies were taken at the same time to measure myeloperoxidase (MPO) activity, a marker of PMN infiltration. In group I, TXB2 level increased from a pre-ischemic value of 2983 +/- 1083 pg/ml to 9483 +/- 2218 pg/ml at 1 hour of reperfusion (p < 0.05) and then decreased to 2386 +/- 1533 pg/ml at 48 hours of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Does iloprost mediate thromboxane activity and polymorphonuclear leukocyte sequestration in ischemic skeletal muscle? Thromboxane is known to alter the endothelial cytoskeleton, thereby causing increased endothelial permeability and polymorphonuclear leukocyte (PMN) sequestration in the lungs. We investigated whether iloprost (a stable prostacyclin analog) can decrease thromboxane activity and consequently PMN sequestration because of its anti-platelet aggregation effect. This premise was investigated in a canine isolated gracilis muscle model using 18 animals. Six animals (group I) had the gracilis muscle subjected to 6 hours of complete ischemia followed by 48 hours of reperfusion. Group II (n = 6) received intravenous infusion of iloprost (0.45 micrograms/kg/hr) throughout the experiment (1 hour preischemia, 6 hours of ischemia and 1 hour of reperfusion) and boluses of 0.45 micrograms/kg 10 minutes before ischemia and reperfusion. Group III (n = 6) underwent a similar ischemic interval, but were given iloprost bolus of 0.45 micrograms/kg followed by intravenous infusion of 0.45 micrograms/kg/hr during 48 hours of reperfusion. Gracilis venous samples were obtained at preischemia (PI) and 1 hour of reperfusion (all 3 groups) and at 48 hours of reperfusion (groups I and III) to measure thromboxane (TXB2) levels. Muscle biopsies were taken at the same time to measure myeloperoxidase (MPO) activity, a marker of PMN infiltration. In group I, TXB2 level increased from a pre-ischemic value of 2983 +/- 1083 pg/ml to 9483 +/- 2218 pg/ml at 1 hour of reperfusion (p < 0.05) and then decreased to 2386 +/- 1533 pg/ml at 48 hours of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280273", "title": "Alpha 1 beta 1 integrin on neural crest cells recognizes some laminin substrata in a Ca(2+)-independent manner.", "content": "Neural crest cells migrate along pathways containing laminin and other extracellular matrix molecules. In the present study, we functionally and biochemically identify an alpha 1 beta 1 integrin heterodimer which bears the HNK-1 epitope on neural crest cells. Using a quantitative cell adhesion assay, we find that this heterodimer mediates attachment to laminin substrata prepared in the presence of Ca2+. Interestingly, neural crest cells bind to laminin-Ca2+ substrata in the presence or absence of divalent cations in the cell attachment medium. In contrast, the attachment of neural crest cells to laminin substrata prepared in the presence of EDTA, heparin, Mg2+, or Mn2+ requires divalent cations. Interactions with these laminin substrata are mediated by a different integrin heterodimer, since antibodies against beta 1 but not alpha 1 integrins inhibit neural crest cell attachment. Thus, the type of laminin substratum appears to dictate the choice of laminin receptor used by neural crest cells. The laminin conformation is determined by the ratio of laminin to Ca2+, though incorporation of heparin during substratum polymerization alters the conformation even in the presence of Ca2+. Once polymerized, the substratum appears stable, not being altered by soaking in either EDTA or divalent cations. Our findings demonstrate: (a) that the alpha 1 beta 1 integrin can bind to some forms of laminin in the absence of soluble divalent cations; (b) that substratum preparation conditions alter the conformation of laminin such that plating laminin in the presence of Ca2+ and/or heparin modulates its configuration; and (c) that neural crest cells utilize different integrins to recognize different laminin conformations.", "contents": "Alpha 1 beta 1 integrin on neural crest cells recognizes some laminin substrata in a Ca(2+)-independent manner. Neural crest cells migrate along pathways containing laminin and other extracellular matrix molecules. In the present study, we functionally and biochemically identify an alpha 1 beta 1 integrin heterodimer which bears the HNK-1 epitope on neural crest cells. Using a quantitative cell adhesion assay, we find that this heterodimer mediates attachment to laminin substrata prepared in the presence of Ca2+. Interestingly, neural crest cells bind to laminin-Ca2+ substrata in the presence or absence of divalent cations in the cell attachment medium. In contrast, the attachment of neural crest cells to laminin substrata prepared in the presence of EDTA, heparin, Mg2+, or Mn2+ requires divalent cations. Interactions with these laminin substrata are mediated by a different integrin heterodimer, since antibodies against beta 1 but not alpha 1 integrins inhibit neural crest cell attachment. Thus, the type of laminin substratum appears to dictate the choice of laminin receptor used by neural crest cells. The laminin conformation is determined by the ratio of laminin to Ca2+, though incorporation of heparin during substratum polymerization alters the conformation even in the presence of Ca2+. Once polymerized, the substratum appears stable, not being altered by soaking in either EDTA or divalent cations. Our findings demonstrate: (a) that the alpha 1 beta 1 integrin can bind to some forms of laminin in the absence of soluble divalent cations; (b) that substratum preparation conditions alter the conformation of laminin such that plating laminin in the presence of Ca2+ and/or heparin modulates its configuration; and (c) that neural crest cells utilize different integrins to recognize different laminin conformations."} {"id": "PMID:1280274", "title": "Dynamics of beta 1 integrin-mediated adhesive contacts in motile fibroblasts.", "content": "Motile chick skeletal fibroblasts adhere to a laminin substrate by means of clustered beta 1 integrins. These integrin \"macroaggregates\" are similar to classic focal contacts but do not appear dark under interference-reflection microscopy. They contain alpha 5 integrin and are associated with extracellular fibronectin. To study their behavior during cell movement, time-lapse, low-light video microscopy was used to image integrins on living cells tagged with a fluorescent anti-beta 1 integrin antibody. Integrin macroaggregates remain fixed with respect to the substratum, despite the fact that they fluctuate in size, density, and shape over a period of minutes. Upon detachment of the cell rear, as much as 85% of the beta 1 integrin density of a macroaggregate remains behind on the substrate, along with both alpha 5 integrin and fibronectin. Release of the cell rear does not involve cleavage of the beta 1 integrin cytoplasmic domain from the remainder of the protein. These results indicate that cell motility does not require regulated detachment of integrin receptors from the substrate. On the other hand, cytoskeletal components and a variable fraction of the integrins are carried forward with the cell during detachment, suggesting that some type of cortical disassembly process does occur. Integrin macroaggregate structures are not recycled intact after detachment of the cell rear from the substrate. They do not persist on the cell surface, nor can they be seen to be engulfed by vesicles; yet, some of the individual integrins that make up these macroaggregates are eventually transported forward by both vesicular and cell-surface routes. Antibody-tagged integrins accumulate in dense patches at the lateral edges and dorsal surface of the cell, and move forward on the cell surface. The tagged integrins also enter cytoplasmic vesicles, which move forward within the cytoplasm. Macroaggregates generally form and grow at the cell front; however, application of fluorescent antibody causes integrins to disappear from the leading edge. Therefore, it has not been possible to directly visualize the recycling of the forward moving tagged integrins into new macroaggregates at the cell front. Surprisingly, under these conditions cells move normally despite the absence of any delivery of tagged integrin to the leading edge, indicating that recycling of integrins to the lamella is not required for apparently normal motility.", "contents": "Dynamics of beta 1 integrin-mediated adhesive contacts in motile fibroblasts. Motile chick skeletal fibroblasts adhere to a laminin substrate by means of clustered beta 1 integrins. These integrin \"macroaggregates\" are similar to classic focal contacts but do not appear dark under interference-reflection microscopy. They contain alpha 5 integrin and are associated with extracellular fibronectin. To study their behavior during cell movement, time-lapse, low-light video microscopy was used to image integrins on living cells tagged with a fluorescent anti-beta 1 integrin antibody. Integrin macroaggregates remain fixed with respect to the substratum, despite the fact that they fluctuate in size, density, and shape over a period of minutes. Upon detachment of the cell rear, as much as 85% of the beta 1 integrin density of a macroaggregate remains behind on the substrate, along with both alpha 5 integrin and fibronectin. Release of the cell rear does not involve cleavage of the beta 1 integrin cytoplasmic domain from the remainder of the protein. These results indicate that cell motility does not require regulated detachment of integrin receptors from the substrate. On the other hand, cytoskeletal components and a variable fraction of the integrins are carried forward with the cell during detachment, suggesting that some type of cortical disassembly process does occur. Integrin macroaggregate structures are not recycled intact after detachment of the cell rear from the substrate. They do not persist on the cell surface, nor can they be seen to be engulfed by vesicles; yet, some of the individual integrins that make up these macroaggregates are eventually transported forward by both vesicular and cell-surface routes. Antibody-tagged integrins accumulate in dense patches at the lateral edges and dorsal surface of the cell, and move forward on the cell surface. The tagged integrins also enter cytoplasmic vesicles, which move forward within the cytoplasm. Macroaggregates generally form and grow at the cell front; however, application of fluorescent antibody causes integrins to disappear from the leading edge. Therefore, it has not been possible to directly visualize the recycling of the forward moving tagged integrins into new macroaggregates at the cell front. Surprisingly, under these conditions cells move normally despite the absence of any delivery of tagged integrin to the leading edge, indicating that recycling of integrins to the lamella is not required for apparently normal motility."} {"id": "PMID:1280275", "title": "Identification of a transitional cell state in the developmental pathway to carrot somatic embryogenesis.", "content": "We have located a novel carbohydrate epitope in the cell walls of certain single cells in embryogenic, but not in non-embryogenic, suspension cultures of carrot. Expression of this epitope, recognized by the mAb JIM8, is regulated during initiation, proliferation, and prolonged growth of suspension cultures such that changes in the abundance of JIM8-reactive cells always precede equivalent changes in embryogenic potential. Therefore, a direct correlation exists between the presence of the JIM8-reactive cell wall epitope and somatic embryo formation. The JIM8-reactive cell wall epitope is expressed in the cell walls of three types of single cells and one type of cell cluster. One of the single cell types seems able to follow one of two phytohormone-controlled developmental pathways, either a cell elongation pathway that eventually leads to cell death, or a cell division pathway that gives rise to proembryogenic masses. We demonstrate that all JIM8-reactive cell types in embryogenic carrot suspension cultures are developmentally related, and that the switch by one of them to somatic embryogenesis is accompanied by the immediate dissipation of the JIM8-reactive cell wall epitope. The cell wall carbohydrate epitope recognized by JIM8 therefore represents a cell wall marker for a very early transitional cell state in the developmental pathway to carrot somatic embryogenesis.", "contents": "Identification of a transitional cell state in the developmental pathway to carrot somatic embryogenesis. We have located a novel carbohydrate epitope in the cell walls of certain single cells in embryogenic, but not in non-embryogenic, suspension cultures of carrot. Expression of this epitope, recognized by the mAb JIM8, is regulated during initiation, proliferation, and prolonged growth of suspension cultures such that changes in the abundance of JIM8-reactive cells always precede equivalent changes in embryogenic potential. Therefore, a direct correlation exists between the presence of the JIM8-reactive cell wall epitope and somatic embryo formation. The JIM8-reactive cell wall epitope is expressed in the cell walls of three types of single cells and one type of cell cluster. One of the single cell types seems able to follow one of two phytohormone-controlled developmental pathways, either a cell elongation pathway that eventually leads to cell death, or a cell division pathway that gives rise to proembryogenic masses. We demonstrate that all JIM8-reactive cell types in embryogenic carrot suspension cultures are developmentally related, and that the switch by one of them to somatic embryogenesis is accompanied by the immediate dissipation of the JIM8-reactive cell wall epitope. The cell wall carbohydrate epitope recognized by JIM8 therefore represents a cell wall marker for a very early transitional cell state in the developmental pathway to carrot somatic embryogenesis."} {"id": "PMID:1280276", "title": "In vitro model of angiogenesis using a human endothelium-derived permanent cell line: contributions of induced gene expression, G-proteins, and integrins.", "content": "The EA hy926 cell line is a continuous, clonable, human cell line that displays a number of features characteristic of vascular endothelial cells (Edgell et al., 1983). Here we report that when EA hy926 cells (EA cells) are plated on an extracellular matrix material [Matrigel], they undergo a process of morphological re-organization leading to the formation of a complex network of cord or tubelike structures. These events seem to resemble, in some respects, an in vitro process of angiogenesis. The morphological re-arrangement occurs within a 12-16 hr period and seems to require expression of new messenger RNA and protein, since it is completely blocked when actinomycin D or cycloheximide are present at the time the cells are plated on Matrigel. This is not due to overt toxicity of the drugs, since exposure of cells to actinomycin D at 2 hr or more after plating on Matrigel has little effect on the formation of the tubelike structures. The process of Matrigel-induced tube formation also apparently involves a G-protein mediated signal. Treatment of the EA cells with pertussis toxin completely blocks the process and causes the ADP-ribosylation of a 42 kD protein that is recognized by an antibody to Gi-alpha subunits. In contrast, concentrations of pertussis toxin sufficient to block tube formation have only modest effects on the adhesion or motility of EA cells on purified matrix components such as laminin or collagen IV. The process of Matrigel-induced tube formation also involves integrins since monoclonal antibodies to integrin alpha 6 or beta 1 subunits can completely block the process. The concentrations of anti-integrin antibodies needed to block tube formation are much lower than those required to block cell adhesion on purified matrix components and are sufficient to occupy less than 10% of the alpha 6 or beta 1 subunits available at the cell surface. These results suggest that integrins may be involved in this potential model of angiogenesis in processes beyond their usual role in cell adhesion. Based on these results, it seems likely that the EA hy 926 cell line will prove to be a useful model for in vitro study of angiogenic processes.", "contents": "In vitro model of angiogenesis using a human endothelium-derived permanent cell line: contributions of induced gene expression, G-proteins, and integrins. The EA hy926 cell line is a continuous, clonable, human cell line that displays a number of features characteristic of vascular endothelial cells (Edgell et al., 1983). Here we report that when EA hy926 cells (EA cells) are plated on an extracellular matrix material [Matrigel], they undergo a process of morphological re-organization leading to the formation of a complex network of cord or tubelike structures. These events seem to resemble, in some respects, an in vitro process of angiogenesis. The morphological re-arrangement occurs within a 12-16 hr period and seems to require expression of new messenger RNA and protein, since it is completely blocked when actinomycin D or cycloheximide are present at the time the cells are plated on Matrigel. This is not due to overt toxicity of the drugs, since exposure of cells to actinomycin D at 2 hr or more after plating on Matrigel has little effect on the formation of the tubelike structures. The process of Matrigel-induced tube formation also apparently involves a G-protein mediated signal. Treatment of the EA cells with pertussis toxin completely blocks the process and causes the ADP-ribosylation of a 42 kD protein that is recognized by an antibody to Gi-alpha subunits. In contrast, concentrations of pertussis toxin sufficient to block tube formation have only modest effects on the adhesion or motility of EA cells on purified matrix components such as laminin or collagen IV. The process of Matrigel-induced tube formation also involves integrins since monoclonal antibodies to integrin alpha 6 or beta 1 subunits can completely block the process. The concentrations of anti-integrin antibodies needed to block tube formation are much lower than those required to block cell adhesion on purified matrix components and are sufficient to occupy less than 10% of the alpha 6 or beta 1 subunits available at the cell surface. These results suggest that integrins may be involved in this potential model of angiogenesis in processes beyond their usual role in cell adhesion. Based on these results, it seems likely that the EA hy 926 cell line will prove to be a useful model for in vitro study of angiogenic processes."} {"id": "PMID:1280277", "title": "Isolation of rat bone marrow mast lineage cells using Thy 1.1 and rat stem cell factor.", "content": "Recent reports have shown that various marrow-derived cell populations respond vigorously to recombinant rat stem cell factor (rrSCF164), one form of the kit-ligand. In the present study, we isolated cell populations from rat bone marrow using the Thy 1.1 antigen (an antigen that in the rat is differentially expressed on primitive hemopoietic progenitor cells) and fluorescently conjugated rrSCF164 (rrSCF164-PE). We show that rrSCF164 only stimulates cells that are enriched in the brightest Thy 1.1 populations (Thy 1.1bright). Numerous cell lines were generated by serial passage in rrSCF164 containing medium, and the prototypic cell lines have been designated SRT002 and SRT003. Each cell line retains the Thy 1.1bright phenotype and does not respond to interleukins (IL) 1-8, IL-10, granulocyte (G) colony-stimulating factor (CSF), granulocyte macrophage (GM) CSF, M-CSF, or crude preparations of mitogen-stimulated T-cell supernatants. The Thy 1.1bright population of rat marrow was subdivided into a subset that binds rrSCF164-PE (Thy 1.1bright, rrSCF164+). The majority of these cells possess certain characteristics in common with marrow-derived mast cells and the Thy 1.1bright, rrSCF164 responsive cell lines, having similar granule morphology, being metachromatic, and reacting positively with alcian blue. Moreover, rats treated with rrSCF164 displayed significant increases in Thy 1.1bright, rrSCF164+ cells in the bone marrow. These studies show that the combination of Thy 1.1 and rrSCF164 makes possible the isolation of a unique subset of rat bone marrow cells that differentially express the Thy 1.1 antigen and the cell surface receptor c-kit, the majority of which are morphologically similar to marrow-derived mast cells.", "contents": "Isolation of rat bone marrow mast lineage cells using Thy 1.1 and rat stem cell factor. Recent reports have shown that various marrow-derived cell populations respond vigorously to recombinant rat stem cell factor (rrSCF164), one form of the kit-ligand. In the present study, we isolated cell populations from rat bone marrow using the Thy 1.1 antigen (an antigen that in the rat is differentially expressed on primitive hemopoietic progenitor cells) and fluorescently conjugated rrSCF164 (rrSCF164-PE). We show that rrSCF164 only stimulates cells that are enriched in the brightest Thy 1.1 populations (Thy 1.1bright). Numerous cell lines were generated by serial passage in rrSCF164 containing medium, and the prototypic cell lines have been designated SRT002 and SRT003. Each cell line retains the Thy 1.1bright phenotype and does not respond to interleukins (IL) 1-8, IL-10, granulocyte (G) colony-stimulating factor (CSF), granulocyte macrophage (GM) CSF, M-CSF, or crude preparations of mitogen-stimulated T-cell supernatants. The Thy 1.1bright population of rat marrow was subdivided into a subset that binds rrSCF164-PE (Thy 1.1bright, rrSCF164+). The majority of these cells possess certain characteristics in common with marrow-derived mast cells and the Thy 1.1bright, rrSCF164 responsive cell lines, having similar granule morphology, being metachromatic, and reacting positively with alcian blue. Moreover, rats treated with rrSCF164 displayed significant increases in Thy 1.1bright, rrSCF164+ cells in the bone marrow. These studies show that the combination of Thy 1.1 and rrSCF164 makes possible the isolation of a unique subset of rat bone marrow cells that differentially express the Thy 1.1 antigen and the cell surface receptor c-kit, the majority of which are morphologically similar to marrow-derived mast cells."} {"id": "PMID:1280278", "title": "Cycloheximide protection against actinomycin D cytotoxicity.", "content": "Pretreatment plus concomitant treatment with 10 micrograms/ml cycloheximide protected Chinese hamster ovary cells and Swiss 3T3 cells against the cytotoxicity of actinomycin D. The cycloheximide treatment reduced the intracellular concentration of actinomycin D by reducing the level of actinomycin D bound to the acid precipitable fraction of the cell. Levels of unbound actinomycin D were unaffected by cycloheximide, indicating that the plasma membrane permeability to AD was not reduced. Actinomycin D inhibited total transcription but did not reduce cytoplasmic levels of rRNA nor of most tested mRNA; however, cytoplasmic levels of c-myc mRNA were reduced below detectability. Cycloheximide treatment further inhibited total transcription and had no effect on cytoplasmic levels of rRNA nor of most tested mRNA. Cytoplasmic levels of c-myc were elevated by cycloheximide and remained so even in the presence of actinomycin D. These data suggested that a reduction in cytoplasmic levels of short lived, essential mRNA, such as c-myc mRNA, was one lethal lesion of actinomycin D. Furthermore, cycloheximide's protection may result, in part, from its ability to stabilize and/or elevate cytoplasmic levels of these mRNA, thus counteracting their depletion by actinomycin D. Protection may also result from the cycloheximide-induced reduction of actinomycin D bound to the acid precipitable fraction of the cells.", "contents": "Cycloheximide protection against actinomycin D cytotoxicity. Pretreatment plus concomitant treatment with 10 micrograms/ml cycloheximide protected Chinese hamster ovary cells and Swiss 3T3 cells against the cytotoxicity of actinomycin D. The cycloheximide treatment reduced the intracellular concentration of actinomycin D by reducing the level of actinomycin D bound to the acid precipitable fraction of the cell. Levels of unbound actinomycin D were unaffected by cycloheximide, indicating that the plasma membrane permeability to AD was not reduced. Actinomycin D inhibited total transcription but did not reduce cytoplasmic levels of rRNA nor of most tested mRNA; however, cytoplasmic levels of c-myc mRNA were reduced below detectability. Cycloheximide treatment further inhibited total transcription and had no effect on cytoplasmic levels of rRNA nor of most tested mRNA. Cytoplasmic levels of c-myc were elevated by cycloheximide and remained so even in the presence of actinomycin D. These data suggested that a reduction in cytoplasmic levels of short lived, essential mRNA, such as c-myc mRNA, was one lethal lesion of actinomycin D. Furthermore, cycloheximide's protection may result, in part, from its ability to stabilize and/or elevate cytoplasmic levels of these mRNA, thus counteracting their depletion by actinomycin D. Protection may also result from the cycloheximide-induced reduction of actinomycin D bound to the acid precipitable fraction of the cells."} {"id": "PMID:1280279", "title": "Characterization of interactions between CCK-33 and CCK receptors in isolated dispersed pancreatic acini.", "content": "In isolated dispersed pancreatic acini, we have characterized the interactions between cholecystokinin (CCK) and CCK receptors by simultaneously measuring CCK-33 immunoreactivity and CCK bioactivity. Incubation of acinar cells with CCK-33 at cell density of 0.2-0.3 mg acinar protein per ml resulted in stimulation of amylase release concomitant with significant and time-dependent decrease of the immunoreactive CCK. With L-364,718 (0.1 microM), a specific CCK receptor antagonist, immunoreactive CCK levels in the media were not significantly altered during incubation; however, CCK-stimulated amylase release was almost completely abolished (94% inhibition). Vasoactive intestinal peptide (1 nM) significantly potentiated CCK stimulated amylase release without affecting immunoreactive CCK in the media. Insulin (167 nM) did not affect the CCK stimulated amylase release or immunoreactive CCK in the media. Incubation of acinar cells with CCK-33 at 4 degrees C did not affect the levels of immunoreactive CCK; however, a significant change in levels of immunoreactive CCK were found at 37 degrees C at 90 min. Incubation of cell free medium with CCK-33 in the presence or absence of secreted enzymes revealed no changes in CCK immunoreactivity in the medium at 90 min. Addition of bacitracin in the incubation media did not affect the CCK immunoreactivity or bioactivity. These findings indicate that in isolated rat pancreatic acini, CCK-33 stimulates amylase release through a receptor that is specifically blocked by L-364,718. Specificity of the interactions of CCK-33 with acinar cells in the media appears to be receptor-mediated and time- and temperature-dependent.", "contents": "Characterization of interactions between CCK-33 and CCK receptors in isolated dispersed pancreatic acini. In isolated dispersed pancreatic acini, we have characterized the interactions between cholecystokinin (CCK) and CCK receptors by simultaneously measuring CCK-33 immunoreactivity and CCK bioactivity. Incubation of acinar cells with CCK-33 at cell density of 0.2-0.3 mg acinar protein per ml resulted in stimulation of amylase release concomitant with significant and time-dependent decrease of the immunoreactive CCK. With L-364,718 (0.1 microM), a specific CCK receptor antagonist, immunoreactive CCK levels in the media were not significantly altered during incubation; however, CCK-stimulated amylase release was almost completely abolished (94% inhibition). Vasoactive intestinal peptide (1 nM) significantly potentiated CCK stimulated amylase release without affecting immunoreactive CCK in the media. Insulin (167 nM) did not affect the CCK stimulated amylase release or immunoreactive CCK in the media. Incubation of acinar cells with CCK-33 at 4 degrees C did not affect the levels of immunoreactive CCK; however, a significant change in levels of immunoreactive CCK were found at 37 degrees C at 90 min. Incubation of cell free medium with CCK-33 in the presence or absence of secreted enzymes revealed no changes in CCK immunoreactivity in the medium at 90 min. Addition of bacitracin in the incubation media did not affect the CCK immunoreactivity or bioactivity. These findings indicate that in isolated rat pancreatic acini, CCK-33 stimulates amylase release through a receptor that is specifically blocked by L-364,718. Specificity of the interactions of CCK-33 with acinar cells in the media appears to be receptor-mediated and time- and temperature-dependent."} {"id": "PMID:1280280", "title": "Interaction of endothelial cells with a laminin A chain peptide (SIKVAV) in vitro and induction of angiogenic behavior in vivo.", "content": "Endothelial cells are known to bind to laminin, and two peptides derived from the laminin A (CTFALRGDNP) and B1 (CDPGYIGSR) chains block the capillary-like tube formation on a laminin-rich basement membrane matrix, Matrigel. In the present study, we have used various in vitro and in vivo assays to investigate the angiogenic-biologic effects of a third active site in the laminin A chain, CSRARKQAASIKVAVSADR (designated PA22-2) on endothelial cells. The SIKVAV-containing peptide was as active as the YIGSR-containing peptide for endothelial cell attachment but was less active than either the RGD-containing peptide or intact laminin. Endothelial cells seeded on this peptide appeared fibroblastic with many extended processes, unlike the normal cobblestone morphology observed on tissue culture plastic. In addition, in contrast to normal tube formation on Matrigel, short irregular structures formed, some of which penetrated the matrix and sprouting was more apparent. Analysis of endothelial cell conditioned media of cells cultured in the presence of this peptide indicated degradation of the Matrigel and zymograms demonstrated active collagenase IV (gelatinase) at 68 and 62 Kd. A murine in vivo angiogenesis assay and the chick yolk sac/chorioallantoic membrane assays with the peptide demonstrated increased endothelial cell mobilization, capillary branching, and vessel formation. These data suggest that the -SIKVAV-site may play an important role in initiating branching and formation of new capillaries from the parent vessels, a behavior that is observed in vivo in response to tumor growth or in the normal vascular response to injury.", "contents": "Interaction of endothelial cells with a laminin A chain peptide (SIKVAV) in vitro and induction of angiogenic behavior in vivo. Endothelial cells are known to bind to laminin, and two peptides derived from the laminin A (CTFALRGDNP) and B1 (CDPGYIGSR) chains block the capillary-like tube formation on a laminin-rich basement membrane matrix, Matrigel. In the present study, we have used various in vitro and in vivo assays to investigate the angiogenic-biologic effects of a third active site in the laminin A chain, CSRARKQAASIKVAVSADR (designated PA22-2) on endothelial cells. The SIKVAV-containing peptide was as active as the YIGSR-containing peptide for endothelial cell attachment but was less active than either the RGD-containing peptide or intact laminin. Endothelial cells seeded on this peptide appeared fibroblastic with many extended processes, unlike the normal cobblestone morphology observed on tissue culture plastic. In addition, in contrast to normal tube formation on Matrigel, short irregular structures formed, some of which penetrated the matrix and sprouting was more apparent. Analysis of endothelial cell conditioned media of cells cultured in the presence of this peptide indicated degradation of the Matrigel and zymograms demonstrated active collagenase IV (gelatinase) at 68 and 62 Kd. A murine in vivo angiogenesis assay and the chick yolk sac/chorioallantoic membrane assays with the peptide demonstrated increased endothelial cell mobilization, capillary branching, and vessel formation. These data suggest that the -SIKVAV-site may play an important role in initiating branching and formation of new capillaries from the parent vessels, a behavior that is observed in vivo in response to tumor growth or in the normal vascular response to injury."} {"id": "PMID:1280281", "title": "Endometrial proteins: a reappraisal.", "content": "Uterine factors influence reproduction at the macro-anatomy level, and the effects of hormonal steroids on endometrial morphology are well recognized in the histopathological diagnosis of dysfunctional bleeding and infertility. During the past decade, attention has been paid to endometrial protein synthesis and secretion with respect to endocrine stimuli and implantation, and to the paracrine/autocrine effects of endometrial peptide growth factors, their binding proteins and other factors. The emphasis of this presentation is on protein secretion of the secretory endometrium, in which progesterone plays a pivotal role. Insulin-like growth factors have receptors on the endometrium, and IGF-binding proteins, stimulated by progesterone, modulate the effects of IGFs locally. Also other protein products of the secretory endometrium have been reviewed in this communication, with special emphasis on studies of a progesterone-associated endometrial protein which has many names in the literature, such as PEP, PP14, alpha 2-PEG and AUP. Extensive studies are ongoing in many laboratories to elucidate the regulation, function, interplay at tissue and cellular levels, and clinical significance of these proteins.", "contents": "Endometrial proteins: a reappraisal. Uterine factors influence reproduction at the macro-anatomy level, and the effects of hormonal steroids on endometrial morphology are well recognized in the histopathological diagnosis of dysfunctional bleeding and infertility. During the past decade, attention has been paid to endometrial protein synthesis and secretion with respect to endocrine stimuli and implantation, and to the paracrine/autocrine effects of endometrial peptide growth factors, their binding proteins and other factors. The emphasis of this presentation is on protein secretion of the secretory endometrium, in which progesterone plays a pivotal role. Insulin-like growth factors have receptors on the endometrium, and IGF-binding proteins, stimulated by progesterone, modulate the effects of IGFs locally. Also other protein products of the secretory endometrium have been reviewed in this communication, with special emphasis on studies of a progesterone-associated endometrial protein which has many names in the literature, such as PEP, PP14, alpha 2-PEG and AUP. Extensive studies are ongoing in many laboratories to elucidate the regulation, function, interplay at tissue and cellular levels, and clinical significance of these proteins."} {"id": "PMID:1280282", "title": "Tyrosine hydroxylase-immunoreactive neurons in the nucleus basalis of the common marmoset (Callithrix jacchus).", "content": "In the course of characterizing the distribution of putative catecholaminergic neurons in the brain of the common marmoset, we encountered a population of such cells in the basal forebrain. Tyrosine hydroxylase-immunoreactive neurons are abundant within the nucleus basalis magnocellularis throughout its entire rostrocaudal extent, but not in other cholinergic basal forebrain nuclei. Most tyrosine hydroxylase-immunoreactive cells are large and multipolar. Double staining with antibodies to choline acetyltransferase or nerve growth factor receptor confirmed that these tyrosine hydroxylase-immunoreactive neurons are cholinergic, and compose at least 40% of the nucleus basalis cholinergic cells. The presence of a catecholamine-synthesizing enzyme in the neurons that provide the major cholinergic input to the neocortex may have important consequences for cortical function, and may be relevant to the vulnerability of the nucleus basalis in certain neurodegenerative disorders.", "contents": "Tyrosine hydroxylase-immunoreactive neurons in the nucleus basalis of the common marmoset (Callithrix jacchus). In the course of characterizing the distribution of putative catecholaminergic neurons in the brain of the common marmoset, we encountered a population of such cells in the basal forebrain. Tyrosine hydroxylase-immunoreactive neurons are abundant within the nucleus basalis magnocellularis throughout its entire rostrocaudal extent, but not in other cholinergic basal forebrain nuclei. Most tyrosine hydroxylase-immunoreactive cells are large and multipolar. Double staining with antibodies to choline acetyltransferase or nerve growth factor receptor confirmed that these tyrosine hydroxylase-immunoreactive neurons are cholinergic, and compose at least 40% of the nucleus basalis cholinergic cells. The presence of a catecholamine-synthesizing enzyme in the neurons that provide the major cholinergic input to the neocortex may have important consequences for cortical function, and may be relevant to the vulnerability of the nucleus basalis in certain neurodegenerative disorders."} {"id": "PMID:1280283", "title": "Design and control of the head retractor muscle in a turtle, Pseudemys (Trachemys) scripta: II. Efferent innervation.", "content": "The head retractor muscle (RCCQ) of Pseudemys scripta is a useful model in which to study the mechanisms animals use to vary the force and timing of movement. Single fibers in this muscle differ significantly in attachments, length, diameter, taper characteristics, and histochemical properties, suggesting that they may be energetically and architecturally specialized for different roles in head movement. In the present paper, we report the peripheral and central efferent innervation of these diverse muscle cells, and we ask how the design of the neural apparatus is matched to the properties of its target muscle fibers. Three out of four bellies in RCCQ are supplied by multiple segmental nerves. The territories of these nerves are separated rostrocaudally within the muscle belly; thus, long muscle fibers cross the territories of two or more segmental nerves. Motor terminals in RCCQ resemble those on frog twitch muscles. Their sizes (length, bouton number) are correlated with the diameters of their target muscle fibers. Each muscle fiber bears 2-14 terminals evenly spaced (approx. 5 mm apart) along its length. Thus, single muscle fibers in RCCQ are multiterminally, and long fibers are multisegmentally innervated. Control experiments indicate that the axons in each segmental nerve arise from different motor neuron populations. Thus, short, in-series fibers are supplied by different motor neurons, and individual long fibers in RCCQ are polyneuronally innervated. These data help explain how long muscle fibers with relatively slow conduction speeds can generate rapid head movements, and they raise questions about the central mechanisms that coordinate the recruitment of RCCQ motor neurons.", "contents": "Design and control of the head retractor muscle in a turtle, Pseudemys (Trachemys) scripta: II. Efferent innervation. The head retractor muscle (RCCQ) of Pseudemys scripta is a useful model in which to study the mechanisms animals use to vary the force and timing of movement. Single fibers in this muscle differ significantly in attachments, length, diameter, taper characteristics, and histochemical properties, suggesting that they may be energetically and architecturally specialized for different roles in head movement. In the present paper, we report the peripheral and central efferent innervation of these diverse muscle cells, and we ask how the design of the neural apparatus is matched to the properties of its target muscle fibers. Three out of four bellies in RCCQ are supplied by multiple segmental nerves. The territories of these nerves are separated rostrocaudally within the muscle belly; thus, long muscle fibers cross the territories of two or more segmental nerves. Motor terminals in RCCQ resemble those on frog twitch muscles. Their sizes (length, bouton number) are correlated with the diameters of their target muscle fibers. Each muscle fiber bears 2-14 terminals evenly spaced (approx. 5 mm apart) along its length. Thus, single muscle fibers in RCCQ are multiterminally, and long fibers are multisegmentally innervated. Control experiments indicate that the axons in each segmental nerve arise from different motor neuron populations. Thus, short, in-series fibers are supplied by different motor neurons, and individual long fibers in RCCQ are polyneuronally innervated. These data help explain how long muscle fibers with relatively slow conduction speeds can generate rapid head movements, and they raise questions about the central mechanisms that coordinate the recruitment of RCCQ motor neurons."} {"id": "PMID:1280284", "title": "Variation in form and axonal termination in the nucleus of the optic tract of the rat: the medial terminal nucleus input on neurons projecting to the inferior olive.", "content": "The nucleus of the optic tract (NOT) and the medial terminal nucleus (MTN) are two primary visual nuclei that take part in circuits sustaining the optokinetic reflex. The morphology of rat NOT cells projecting to the inferior olive (NOT-IO neurons) and their terminal input, specifically terminals originating from the MTN, have been studied in the rat at the light and electron microscopical level. This has been done by means of combined retrograde tracing from the inferior olive and anterograde tracing from the MTN to the NOT. The area containing MTN terminal fibers and the area occupied by NOT-IO neurons has been found to match. This matched distribution provides a more detailed description of the NOT, with possible functional implications. Identified NOT-IO neurons demonstrate considerable variability in their dendritic branching pattern and have been found to include all neuronal cell types described for the NOT. The dendritic branching pattern of NOT-IO cells could be related to the orientation and distribution of the NOT's major afferent fiber systems. NOT-IO neurons receive a variable MTN and retinal input onto their somata, comparable to other cells in the NOT. With exception of the superficial part of the NOT, NOT-IO neurons with the most MTN terminals were found dorsally in areas containing large numbers of MTN terminals. In conclusion, although NOT-IO neurons are uniform with respect to their receptive field properties, they vary considerably with respect to the shape of the cell body, dendritic branching pattern, and terminal input. This means that morphological characteristics of NOT-IO neurons have no predictive value with regard to their receptive field properties.", "contents": "Variation in form and axonal termination in the nucleus of the optic tract of the rat: the medial terminal nucleus input on neurons projecting to the inferior olive. The nucleus of the optic tract (NOT) and the medial terminal nucleus (MTN) are two primary visual nuclei that take part in circuits sustaining the optokinetic reflex. The morphology of rat NOT cells projecting to the inferior olive (NOT-IO neurons) and their terminal input, specifically terminals originating from the MTN, have been studied in the rat at the light and electron microscopical level. This has been done by means of combined retrograde tracing from the inferior olive and anterograde tracing from the MTN to the NOT. The area containing MTN terminal fibers and the area occupied by NOT-IO neurons has been found to match. This matched distribution provides a more detailed description of the NOT, with possible functional implications. Identified NOT-IO neurons demonstrate considerable variability in their dendritic branching pattern and have been found to include all neuronal cell types described for the NOT. The dendritic branching pattern of NOT-IO cells could be related to the orientation and distribution of the NOT's major afferent fiber systems. NOT-IO neurons receive a variable MTN and retinal input onto their somata, comparable to other cells in the NOT. With exception of the superficial part of the NOT, NOT-IO neurons with the most MTN terminals were found dorsally in areas containing large numbers of MTN terminals. In conclusion, although NOT-IO neurons are uniform with respect to their receptive field properties, they vary considerably with respect to the shape of the cell body, dendritic branching pattern, and terminal input. This means that morphological characteristics of NOT-IO neurons have no predictive value with regard to their receptive field properties."} {"id": "PMID:1280285", "title": "Immunohistochemical study on development of serotonin-, substance P-, and enkephalin-positive fibers in the rat spinal motor nucleus.", "content": "Developmental changes in the coexistence of serotonin and substance P/enkephalin within single fibers of lamina IX of the rat lumbar spinal cord were examined by the use of a double-labelling immunohistochemical technique. On postnatal day (P) 0, 65.0% of immunoreactive varicosities contained only serotonin, and 21.3% of them had both serotonin and substance P. The coexistent ratio of serotonin and substance P in single fibers increased with development: 61.9% of serotonin positive varicosities co-contained substance P on P28, similar to the ratio found in adult animals (67.4%). The ratios of varicosities containing only substance P remained the same from P0 to adult stage (about 15%). Enkephalin positive immunoreactivity was not co-localized with serotonin positive varicosities at any stage of development. Although numerous serotonin positive fibers were found in lamina IX, only a few substance P and enkephalin positive fibers were observed in the same area on P0. The density of serotonin positive varicosities increased slightly by P28, whereas substance P and enkephalin positive fibers increased considerably by this age. Between P28 and the adult stage, the density of serotonin positive fibers decreased by about 50%. The cross sectional area of axonal varicosities containing serotonin- and substance P-like immunoreactivity was similar in both P0 and adult animals, whereas that of enkephalin positive fibers was different. We also examined the coexistence of serotonin and substance P within single neurons of the caudal raphe nuclei in P7 and adult animals, and found that the coexistent ratio significantly increased with development.", "contents": "Immunohistochemical study on development of serotonin-, substance P-, and enkephalin-positive fibers in the rat spinal motor nucleus. Developmental changes in the coexistence of serotonin and substance P/enkephalin within single fibers of lamina IX of the rat lumbar spinal cord were examined by the use of a double-labelling immunohistochemical technique. On postnatal day (P) 0, 65.0% of immunoreactive varicosities contained only serotonin, and 21.3% of them had both serotonin and substance P. The coexistent ratio of serotonin and substance P in single fibers increased with development: 61.9% of serotonin positive varicosities co-contained substance P on P28, similar to the ratio found in adult animals (67.4%). The ratios of varicosities containing only substance P remained the same from P0 to adult stage (about 15%). Enkephalin positive immunoreactivity was not co-localized with serotonin positive varicosities at any stage of development. Although numerous serotonin positive fibers were found in lamina IX, only a few substance P and enkephalin positive fibers were observed in the same area on P0. The density of serotonin positive varicosities increased slightly by P28, whereas substance P and enkephalin positive fibers increased considerably by this age. Between P28 and the adult stage, the density of serotonin positive fibers decreased by about 50%. The cross sectional area of axonal varicosities containing serotonin- and substance P-like immunoreactivity was similar in both P0 and adult animals, whereas that of enkephalin positive fibers was different. We also examined the coexistence of serotonin and substance P within single neurons of the caudal raphe nuclei in P7 and adult animals, and found that the coexistent ratio significantly increased with development."} {"id": "PMID:1280288", "title": "Detection of hepatitis C virus antibodies with new recombinant antigens: assessment in chronic liver diseases.", "content": "A new serological assay to detect antibodies against hepatitis C, based on a recombinant protein (BHC10) which incorporates structural and non-structural viral antigens, was tested in 67 healthy subjects and 409 patients with various forms of liver disease. Results were compared with the current assay based on the recombinant non-structural viral antigen c100 and with the recently introduced second-generation assay, Ortho2. None of the healthy subjects was positive by any of the assays. In patients with chronic non-A, non-B hepatitis the prevalence of anti-BHC10 was 96.8%, higher than anti-c100 (83.3%, p less than 0.001) and similar to Ortho2 (94.3%). False-positive results were less frequently found when BHC10 was used. These findings show that assays incorporating structural and non-structural antigens provide higher sensitivity to detect hepatitis C virus infection and they define an almost exclusive role of hepatitis C virus in the genesis of chronic non-A, non-B hepatitis.", "contents": "Detection of hepatitis C virus antibodies with new recombinant antigens: assessment in chronic liver diseases. A new serological assay to detect antibodies against hepatitis C, based on a recombinant protein (BHC10) which incorporates structural and non-structural viral antigens, was tested in 67 healthy subjects and 409 patients with various forms of liver disease. Results were compared with the current assay based on the recombinant non-structural viral antigen c100 and with the recently introduced second-generation assay, Ortho2. None of the healthy subjects was positive by any of the assays. In patients with chronic non-A, non-B hepatitis the prevalence of anti-BHC10 was 96.8%, higher than anti-c100 (83.3%, p less than 0.001) and similar to Ortho2 (94.3%). False-positive results were less frequently found when BHC10 was used. These findings show that assays incorporating structural and non-structural antigens provide higher sensitivity to detect hepatitis C virus infection and they define an almost exclusive role of hepatitis C virus in the genesis of chronic non-A, non-B hepatitis."} {"id": "PMID:1280286", "title": "[The quantitative assessment of the biological activity of angiogenin].", "content": "Methods have been developed for the in vivo quantitative estimation of biological activity of angiogenin, a protein growth factor of blood vessels. The quantitative analysis of angiogenin with the methods of angiogenetic disks in isotopic modification requires nanogram amounts of the angiogenetic. The cutireaction test is less sensitive though technically simple. The methods are developed on animal (mouse and rat) tissues.", "contents": "[The quantitative assessment of the biological activity of angiogenin]. Methods have been developed for the in vivo quantitative estimation of biological activity of angiogenin, a protein growth factor of blood vessels. The quantitative analysis of angiogenin with the methods of angiogenetic disks in isotopic modification requires nanogram amounts of the angiogenetic. The cutireaction test is less sensitive though technically simple. The methods are developed on animal (mouse and rat) tissues."} {"id": "PMID:1280289", "title": "Detection of hepatitis C viral RNA sequences in fresh and paraffin-embedded liver biopsy specimens of non-A, non-B hepatitis patients.", "content": "In this study methods of HCV-RNA detection in fresh frozen and formalin-fixed, paraffin-embedded liver biopsies are described. Of 22 untreated chronic non-A, non-B hepatitis patients and 6 control patients, a plasma sample and part of a liver biopsy were freshly frozen for hepatitis C virus (HCV) cDNA-PCR. From 16 of the same non-A, non-B hepatitis patients and from 5 of the same control patients formalin-fixed, paraffin-embedded liver tissue from the same biopsy was available also for HCV cDNA-PCR. In 13 of 22 non-A, non-B hepatitis patients HCV-RNA could be detected in plasma as well as in liver tissue. In the other 9 non-A, non-B hepatitis patients and in 6 control patients, no HCV-RNA was detectable in either plasma or liver tissue. The comparison between HCV cDNA-PCR results in fresh frozen versus formalin-fixed, paraffin-embedded liver biopsies showed that although detection of HCV-RNA in both correlated 100% the quantity of HCV-RNA was lower in the formalin-fixed, paraffin-embedded liver biopsies of 5 of 8 patients for whom end-point dilution titration of liver RNA was performed. We conclude that using the procedures described HCV-RNA can be reliably detected in both fresh-frozen and formalin-fixed, paraffin-embedded liver biopsies and that HCV cDNA-PCR in liver tissue may become an important assay, especially for monitoring anti-viral therapy.", "contents": "Detection of hepatitis C viral RNA sequences in fresh and paraffin-embedded liver biopsy specimens of non-A, non-B hepatitis patients. In this study methods of HCV-RNA detection in fresh frozen and formalin-fixed, paraffin-embedded liver biopsies are described. Of 22 untreated chronic non-A, non-B hepatitis patients and 6 control patients, a plasma sample and part of a liver biopsy were freshly frozen for hepatitis C virus (HCV) cDNA-PCR. From 16 of the same non-A, non-B hepatitis patients and from 5 of the same control patients formalin-fixed, paraffin-embedded liver tissue from the same biopsy was available also for HCV cDNA-PCR. In 13 of 22 non-A, non-B hepatitis patients HCV-RNA could be detected in plasma as well as in liver tissue. In the other 9 non-A, non-B hepatitis patients and in 6 control patients, no HCV-RNA was detectable in either plasma or liver tissue. The comparison between HCV cDNA-PCR results in fresh frozen versus formalin-fixed, paraffin-embedded liver biopsies showed that although detection of HCV-RNA in both correlated 100% the quantity of HCV-RNA was lower in the formalin-fixed, paraffin-embedded liver biopsies of 5 of 8 patients for whom end-point dilution titration of liver RNA was performed. We conclude that using the procedures described HCV-RNA can be reliably detected in both fresh-frozen and formalin-fixed, paraffin-embedded liver biopsies and that HCV cDNA-PCR in liver tissue may become an important assay, especially for monitoring anti-viral therapy."} {"id": "PMID:1280287", "title": "Transdermal 17 beta-estradiol combined with oral progestogen increases plasma levels of insulin-like growth factor-I in postmenopausal women.", "content": "In order to evaluate the effect of postmenopausal estrogen replacement therapy on the plasma levels of the insulin-like growth factor-I (IGF-I) 12 postmenopausal women aged 44 to 59 years were studied. The control group consisted of 15 healthy premenopausal women aged 20-44 years. In the postmenopausal women the plasma levels of IGF-I, gonadotrophins and sex hormones were determined before and after 3 and 6 months cyclic replacement therapy with transdermal 17 beta-estradiol (E2 100 micrograms patches applied twice weekly) combined with oral chlormadinone acetate (2 mg daily for 7 days in each cycle). Basal levels of estradiol (E2), IGF-I, dehydroepiandrosterone sulphate (DHEA-S), testosterone and androstenedione were lower, but gonadotropin levels were higher in postmenopausal than in premenopausal women. In all the women studied age was inversely correlated with IGF-I levels (r = -0.793, p less than 0.001) and with DHEA-S concentrations (r = -0.435, p less than 0.02). In postmenopausal women transdermal estradiol administration restored the circulating E2 levels to the early follicular range and increased the IGF-I levels (from 76.4 +/- 9.2 micrograms/l to 141.8 +/- 20.8 micrograms/l; p less than 0.01). Transdermal estradiol decreased gonadotrophin levels without changes in concentration of DHEA-S, testosterone, androstenedione and SHBG. In postmenopausal women before and during replacement therapy a positive correlation was found between estradiol and IGF-I concentrations (r = -0.439, p less than 0.01). These results suggest that cyclic replacement therapy with transdermal 17 beta-estradiol in combination with chlormadinone acetate given orally increase the plasma levels of IGF-I in postmenopausal women.", "contents": "Transdermal 17 beta-estradiol combined with oral progestogen increases plasma levels of insulin-like growth factor-I in postmenopausal women. In order to evaluate the effect of postmenopausal estrogen replacement therapy on the plasma levels of the insulin-like growth factor-I (IGF-I) 12 postmenopausal women aged 44 to 59 years were studied. The control group consisted of 15 healthy premenopausal women aged 20-44 years. In the postmenopausal women the plasma levels of IGF-I, gonadotrophins and sex hormones were determined before and after 3 and 6 months cyclic replacement therapy with transdermal 17 beta-estradiol (E2 100 micrograms patches applied twice weekly) combined with oral chlormadinone acetate (2 mg daily for 7 days in each cycle). Basal levels of estradiol (E2), IGF-I, dehydroepiandrosterone sulphate (DHEA-S), testosterone and androstenedione were lower, but gonadotropin levels were higher in postmenopausal than in premenopausal women. In all the women studied age was inversely correlated with IGF-I levels (r = -0.793, p less than 0.001) and with DHEA-S concentrations (r = -0.435, p less than 0.02). In postmenopausal women transdermal estradiol administration restored the circulating E2 levels to the early follicular range and increased the IGF-I levels (from 76.4 +/- 9.2 micrograms/l to 141.8 +/- 20.8 micrograms/l; p less than 0.01). Transdermal estradiol decreased gonadotrophin levels without changes in concentration of DHEA-S, testosterone, androstenedione and SHBG. In postmenopausal women before and during replacement therapy a positive correlation was found between estradiol and IGF-I concentrations (r = -0.439, p less than 0.01). These results suggest that cyclic replacement therapy with transdermal 17 beta-estradiol in combination with chlormadinone acetate given orally increase the plasma levels of IGF-I in postmenopausal women."} {"id": "PMID:1280291", "title": "[Connections of the posterior region of the thalamus in rats].", "content": "Using retrograde and anterograde tracing methods we have studied in the posterior region of the thalamus of the rat the distribution of: (1) the terminal fields of the main afferents arising from somatosensory centers (dorsal column nuclei, interpolar trigeminal subnucleus, somatosensory cortex), motor centers (red nucleus, motor cortex) and multimodal structures (deep layers of the superior colliculus, zona incerta, cingular cortex) and of (2) the neurons giving rise to the main efferents towards the sensorimotor cortex, the red nucleus, the deep layers of the superior colliculus and the zone incerta. The overlap of the retrograde and anterograde labeling reveals a relatively homogeneous region. Considering however the cortical connections, three different subdivisions can be distinguished: a caudal pole completely devoid of cortical connections, a medial subdivision receiving cortical afferents from the sensorimotor and cingulate cortices and a rostral pole reciprocally connected with the sensorimotor cortex. Therefore the rostral pole would be the only part of this region which should be included in the thalamus.", "contents": "[Connections of the posterior region of the thalamus in rats]. Using retrograde and anterograde tracing methods we have studied in the posterior region of the thalamus of the rat the distribution of: (1) the terminal fields of the main afferents arising from somatosensory centers (dorsal column nuclei, interpolar trigeminal subnucleus, somatosensory cortex), motor centers (red nucleus, motor cortex) and multimodal structures (deep layers of the superior colliculus, zona incerta, cingular cortex) and of (2) the neurons giving rise to the main efferents towards the sensorimotor cortex, the red nucleus, the deep layers of the superior colliculus and the zone incerta. The overlap of the retrograde and anterograde labeling reveals a relatively homogeneous region. Considering however the cortical connections, three different subdivisions can be distinguished: a caudal pole completely devoid of cortical connections, a medial subdivision receiving cortical afferents from the sensorimotor and cingulate cortices and a rostral pole reciprocally connected with the sensorimotor cortex. Therefore the rostral pole would be the only part of this region which should be included in the thalamus."} {"id": "PMID:1280292", "title": "The central connections of the olfactory bulbs in cod, Gadus morhua L.", "content": "The central projections of the \"classical\" olfactory system of the cod, Gadus morhua were examined with horseradish peroxidase and cobalt tracing techniques. Label was applied to the olfactory bulb or selectively to central stumps of sectioned individual olfactory tract bundlets. The olfactory bulb projects bilaterally to restricted areas of the dorsolateral, ventromedial and basolateral telencephalon, anterior commissural and preoptic areas, habenular nuclei, dorsal thalamus and to the nucleus posterior tuberis in the diencephalon. An interbulbar connection courses in the medial olfactory tract (MOT). Contralateral projections were less pronounced than on the ipsilateral side. More specifically, the lateral olfactory tract (LOT) projects ipsilaterally to the telencephalon into the Dlv, Dc, Vs and Dp areas. The lateral bundlet of the medial olfactory tract (IMOT) terminates in the Dlv and Dc areas. The medial bundlet of the medial olfactory tract (mMOT) terminates in Vv and Vd. The fused lMOT and mMOT project to the caudal telencephalon in the Vs and Dp. Neurons projecting to the olfactory bulb were located bilaterally in the telencephalon. The majority of the bulbopetal fibers course via the lateral part of the MOT; a few neurons also project to the bulb through the other bundlets of the olfactory tract. The results are compared with previous studies on the olfactory projections of other teleost species and discussed with respect to the reported functional differentiation of the olfactory system in teleosts.", "contents": "The central connections of the olfactory bulbs in cod, Gadus morhua L. The central projections of the \"classical\" olfactory system of the cod, Gadus morhua were examined with horseradish peroxidase and cobalt tracing techniques. Label was applied to the olfactory bulb or selectively to central stumps of sectioned individual olfactory tract bundlets. The olfactory bulb projects bilaterally to restricted areas of the dorsolateral, ventromedial and basolateral telencephalon, anterior commissural and preoptic areas, habenular nuclei, dorsal thalamus and to the nucleus posterior tuberis in the diencephalon. An interbulbar connection courses in the medial olfactory tract (MOT). Contralateral projections were less pronounced than on the ipsilateral side. More specifically, the lateral olfactory tract (LOT) projects ipsilaterally to the telencephalon into the Dlv, Dc, Vs and Dp areas. The lateral bundlet of the medial olfactory tract (IMOT) terminates in the Dlv and Dc areas. The medial bundlet of the medial olfactory tract (mMOT) terminates in Vv and Vd. The fused lMOT and mMOT project to the caudal telencephalon in the Vs and Dp. Neurons projecting to the olfactory bulb were located bilaterally in the telencephalon. The majority of the bulbopetal fibers course via the lateral part of the MOT; a few neurons also project to the bulb through the other bundlets of the olfactory tract. The results are compared with previous studies on the olfactory projections of other teleost species and discussed with respect to the reported functional differentiation of the olfactory system in teleosts."} {"id": "PMID:1280293", "title": "Postnatal changes in development of serotonin-, neuropeptide Y-, Leu-enkephalin- and substance P- terminals in the rat locus coeruleus; a quantitative immunohistochemical study.", "content": "Postnatal developmental changes were investigated in afferent terminals immunoreactive to serotonin (5-HT), neuropeptide Y (NPY), Leu-Enkephalin (ENK) and substance P (SP) within the locus coeruleus from postnatal rat from day 1 (1 D) to 9 week (9 W) adult using immunohistochemical techniques. Quantitative study using a light microscopic image analyzing system revealed that the number of immunoreactive terminals increased after birth to reach a peak at 5 W, then decreased by 26% of this value and stabilized at 7 W; terminals immunoreactive to 5-HT or NPY increased gradually after birth, while those immunoreactive to ENK or SP increased suddenly at 3 W. Electron microscopic analysis revealed similar changes in the total terminal number during development. Synaptic terminals, on the other hand, increased sharply from 1 D to 3 W, then gradually until 5 W, and remained stable thereafter. These results suggest that surplus afferent terminals are eliminated prior to the establishment of afferent innervation and that 5 W postnatal is the critical time for maturation of the afferent system. Electron microscopy also demonstrated morphological characteristics of terminals immunoreactive to each peptide or 5-HT and developmental changes in their characteristics.", "contents": "Postnatal changes in development of serotonin-, neuropeptide Y-, Leu-enkephalin- and substance P- terminals in the rat locus coeruleus; a quantitative immunohistochemical study. Postnatal developmental changes were investigated in afferent terminals immunoreactive to serotonin (5-HT), neuropeptide Y (NPY), Leu-Enkephalin (ENK) and substance P (SP) within the locus coeruleus from postnatal rat from day 1 (1 D) to 9 week (9 W) adult using immunohistochemical techniques. Quantitative study using a light microscopic image analyzing system revealed that the number of immunoreactive terminals increased after birth to reach a peak at 5 W, then decreased by 26% of this value and stabilized at 7 W; terminals immunoreactive to 5-HT or NPY increased gradually after birth, while those immunoreactive to ENK or SP increased suddenly at 3 W. Electron microscopic analysis revealed similar changes in the total terminal number during development. Synaptic terminals, on the other hand, increased sharply from 1 D to 3 W, then gradually until 5 W, and remained stable thereafter. These results suggest that surplus afferent terminals are eliminated prior to the establishment of afferent innervation and that 5 W postnatal is the critical time for maturation of the afferent system. Electron microscopy also demonstrated morphological characteristics of terminals immunoreactive to each peptide or 5-HT and developmental changes in their characteristics."} {"id": "PMID:1280294", "title": "Immunocytochemistry of oculomotor afferents in the squirrel monkey (Saimiri sciureus).", "content": "Attempts were made to co-define afferents of the oculomotor nuclear complex (OMC) and their putative neurotransmitters in the squirrel monkey. Wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and wheat germ agglutinin conjugated to enzymatically inactive HRP and coupled to colloidal gold (WGAapoHRP-AU) were used as retrograde tracers in combination with immunocytochemical methods. Primarily unilateral injections were made into portions of the OMC. Stabilized tetramethylbenzidine (TMB) and silver enhanced sections were immunoreacted with antisera for choline acetyltransferase (ChAT), glutamate (GLU), aspartate (ASP), aminobutyric acid (GABA), serotonin (5-HT) and cholecystokinin (CCK). Moderate numbers of ChAT-IR neurons in caudal regions of the medial vestibular nuclei (MVN) projected to the OMC. Tracer labeled ChAT-IR cells in the MVN projected ipsilaterally to the ventral nucleus (medial rectus subdivision) of the OMC and bilaterally with contralateral dominance to other OMC subdivisions. Cholinergic neurons in the dorsal paragigantocellular reticular nucleus (DPG) projected bilaterally to each half of the OMC. Cells of the DPG, considered to contain inhibitory burst neurons impinging upon the contralateral abducens nucleus, were shown to project to virtually all subdivision of the OMC. Abducens motor neurons were ChAT-IR, but abducens internuclear neurons were not. Cells in caudal parts of the nucleus prepositus (NPP) projecting to the ipsilateral ventral nucleus of the OMC were not ChAT-positive; ChAT-IR cells in rostral NPP did not project to the OMC. Unilateral OMC injections labeled cells ipsilaterally in the RiMLF, contralaterally in the pretectal olivary nucleus, the interstitial nucleus of Cajal and the infracerebellar nucleus and bilaterally in the superior vestibular nucleus, none of which were ChAT-IR. A small number of cells in the locus ceruleus projected ipsilaterally to the OMC. Although large numbers of vestibular neurons were GLU-IR and ASP-IR, only a few tracer labeled ASP-IR neurons in the contralateral MVN projected to the OMC. No other GLU- or ASP-positive neurons were immunoreactive for GABA, 5-HT or CCK, but cells of the lateral vestibular nucleus were surrounded by CCK-IR fibers and terminals.", "contents": "Immunocytochemistry of oculomotor afferents in the squirrel monkey (Saimiri sciureus). Attempts were made to co-define afferents of the oculomotor nuclear complex (OMC) and their putative neurotransmitters in the squirrel monkey. Wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) and wheat germ agglutinin conjugated to enzymatically inactive HRP and coupled to colloidal gold (WGAapoHRP-AU) were used as retrograde tracers in combination with immunocytochemical methods. Primarily unilateral injections were made into portions of the OMC. Stabilized tetramethylbenzidine (TMB) and silver enhanced sections were immunoreacted with antisera for choline acetyltransferase (ChAT), glutamate (GLU), aspartate (ASP), aminobutyric acid (GABA), serotonin (5-HT) and cholecystokinin (CCK). Moderate numbers of ChAT-IR neurons in caudal regions of the medial vestibular nuclei (MVN) projected to the OMC. Tracer labeled ChAT-IR cells in the MVN projected ipsilaterally to the ventral nucleus (medial rectus subdivision) of the OMC and bilaterally with contralateral dominance to other OMC subdivisions. Cholinergic neurons in the dorsal paragigantocellular reticular nucleus (DPG) projected bilaterally to each half of the OMC. Cells of the DPG, considered to contain inhibitory burst neurons impinging upon the contralateral abducens nucleus, were shown to project to virtually all subdivision of the OMC. Abducens motor neurons were ChAT-IR, but abducens internuclear neurons were not. Cells in caudal parts of the nucleus prepositus (NPP) projecting to the ipsilateral ventral nucleus of the OMC were not ChAT-positive; ChAT-IR cells in rostral NPP did not project to the OMC. Unilateral OMC injections labeled cells ipsilaterally in the RiMLF, contralaterally in the pretectal olivary nucleus, the interstitial nucleus of Cajal and the infracerebellar nucleus and bilaterally in the superior vestibular nucleus, none of which were ChAT-IR. A small number of cells in the locus ceruleus projected ipsilaterally to the OMC. Although large numbers of vestibular neurons were GLU-IR and ASP-IR, only a few tracer labeled ASP-IR neurons in the contralateral MVN projected to the OMC. No other GLU- or ASP-positive neurons were immunoreactive for GABA, 5-HT or CCK, but cells of the lateral vestibular nucleus were surrounded by CCK-IR fibers and terminals."} {"id": "PMID:1280295", "title": "EM and EM Golgi study on structure of nucleus rotundus in chicks.", "content": "The analysis of EM structure of nucleus rotundus completes the results got by Golgi study. The fine structure of neurons and neuropil of the nucleus and the synaptic relations were studied by EM. The fine structural details of principal neuron were described. Several synapses of symmetrical type with flattened vesicles in large terminals contacted the cell body and also the origin and proximal part of the main dendrites. In the neuropil synaptic junctions were formed by terminals that contained (1) spherical vesicles with occasionally very few dense core vesicles, (2) flattened synaptic vesicles. Terminals that contained spherical vesicles were associated with asymmetric synaptic densities, and terminals that contained flattened vesicles formed symmetric junctions. Synapses of asymmetric type associated mostly with terminal sections of dendrites forming glomerular-like structure. Synapses of symmetric type with flattened synaptic vesicles contacted the branching areas of dendritic terminals and side-branches, the origin of main dendrites and the cell surface of principal neuron.", "contents": "EM and EM Golgi study on structure of nucleus rotundus in chicks. The analysis of EM structure of nucleus rotundus completes the results got by Golgi study. The fine structure of neurons and neuropil of the nucleus and the synaptic relations were studied by EM. The fine structural details of principal neuron were described. Several synapses of symmetrical type with flattened vesicles in large terminals contacted the cell body and also the origin and proximal part of the main dendrites. In the neuropil synaptic junctions were formed by terminals that contained (1) spherical vesicles with occasionally very few dense core vesicles, (2) flattened synaptic vesicles. Terminals that contained spherical vesicles were associated with asymmetric synaptic densities, and terminals that contained flattened vesicles formed symmetric junctions. Synapses of asymmetric type associated mostly with terminal sections of dendrites forming glomerular-like structure. Synapses of symmetric type with flattened synaptic vesicles contacted the branching areas of dendritic terminals and side-branches, the origin of main dendrites and the cell surface of principal neuron."} {"id": "PMID:1280296", "title": "A novel antibody from rheumatoid arthritis patients.", "content": "A 106 base-pair length DNA sequence was isolated from rheumatoid synovium. Base sequence analysis showed this fragment to correspond to sequences already reported as the non-transcribed spacer of ribosomal DNA. Base sequence analysis also revealed that a fused protein has a unique five amino acid sequence. This five amino acid sequence was considered to be an epitope for an antibody. This antibody was named BUNGO antibody (BUNGO is the old name for Oita prefecture). An antigen peptide was synthesized chemically in accordance with the amino acid sequence of the epitope. Using this synthetic peptide, BUNGO antibody in serum was measured. Twelve of 32 patients (37.5%) with RA (rheumatoid arthritis) tested positive for the antibody. Five of 32 (15.6%) age and sex-matched control subjects were positive, indicating a significant difference from the RA group (chi 2 = 3.9, p < 0.05).", "contents": "A novel antibody from rheumatoid arthritis patients. A 106 base-pair length DNA sequence was isolated from rheumatoid synovium. Base sequence analysis showed this fragment to correspond to sequences already reported as the non-transcribed spacer of ribosomal DNA. Base sequence analysis also revealed that a fused protein has a unique five amino acid sequence. This five amino acid sequence was considered to be an epitope for an antibody. This antibody was named BUNGO antibody (BUNGO is the old name for Oita prefecture). An antigen peptide was synthesized chemically in accordance with the amino acid sequence of the epitope. Using this synthetic peptide, BUNGO antibody in serum was measured. Twelve of 32 patients (37.5%) with RA (rheumatoid arthritis) tested positive for the antibody. Five of 32 (15.6%) age and sex-matched control subjects were positive, indicating a significant difference from the RA group (chi 2 = 3.9, p < 0.05)."} {"id": "PMID:1280297", "title": "[Experimental study of hyperostosis induced by hypervitaminosis A].", "content": "Radiological and histological studies were made on retinoid-induced hyperostosis in rats. Vitamin A (VA) was administered intraperitoneally in rats for 6 months. Hyperostosis was observed in 94 percent of rats administered VA and in 38 percent of the control. Chondrocytes and vascular proliferation were observed in the attachment of the tendons and in the anterior corner of the vertebral body after 3 months. Hyperostosis was observed as osteophytes in the attachment of ligaments or tendons and as heterotopic ossification in the tendons or the joint capsules of the whole body after 6 months. Immature cells were observed around the osteophytes. These areas were stained with pH 4.1 toluidine blue and disappeared following streptomyces hyaluronidase treatment. This would indicate that hyaluronic acid increased around these areas. These results appear to demonstrate that hypervitaminosis A is capable of producing hyperostosis.", "contents": "[Experimental study of hyperostosis induced by hypervitaminosis A]. Radiological and histological studies were made on retinoid-induced hyperostosis in rats. Vitamin A (VA) was administered intraperitoneally in rats for 6 months. Hyperostosis was observed in 94 percent of rats administered VA and in 38 percent of the control. Chondrocytes and vascular proliferation were observed in the attachment of the tendons and in the anterior corner of the vertebral body after 3 months. Hyperostosis was observed as osteophytes in the attachment of ligaments or tendons and as heterotopic ossification in the tendons or the joint capsules of the whole body after 6 months. Immature cells were observed around the osteophytes. These areas were stained with pH 4.1 toluidine blue and disappeared following streptomyces hyaluronidase treatment. This would indicate that hyaluronic acid increased around these areas. These results appear to demonstrate that hypervitaminosis A is capable of producing hyperostosis."} {"id": "PMID:1280298", "title": "Diagnostic approaches to the patient with suspected food allergies.", "content": "Adverse food reactions may be secondary to food allergy (hypersensitivity) or food intolerance. The clinical manifestations of food allergies depend on the target organ affected. Gastrointestinal, respiratory, and cutaneous symptoms are the most common of the clinical responses. The medical history, physical examination, and various in vivo or in vitro tests are useful in the diagnostic evaluation. Double-blind, placebo-controlled food challenges are the standard for diagnosis of food allergies. Presumptive diagnosis of food allergy based on patient history and on results of skin test or radioallergosorbent test is no longer acceptable, except in cases of severe anaphylaxis after an isolated ingestion of a specific food. Unless the physician provides an unequivocal diagnosis of food allergy, people will continue to alter their eating habits on the basis of misconceptions of food allergy.", "contents": "Diagnostic approaches to the patient with suspected food allergies. Adverse food reactions may be secondary to food allergy (hypersensitivity) or food intolerance. The clinical manifestations of food allergies depend on the target organ affected. Gastrointestinal, respiratory, and cutaneous symptoms are the most common of the clinical responses. The medical history, physical examination, and various in vivo or in vitro tests are useful in the diagnostic evaluation. Double-blind, placebo-controlled food challenges are the standard for diagnosis of food allergies. Presumptive diagnosis of food allergy based on patient history and on results of skin test or radioallergosorbent test is no longer acceptable, except in cases of severe anaphylaxis after an isolated ingestion of a specific food. Unless the physician provides an unequivocal diagnosis of food allergy, people will continue to alter their eating habits on the basis of misconceptions of food allergy."} {"id": "PMID:1280299", "title": "Development of a competitive radioimmunoassay and a sandwich enzyme-linked immunosorbent assay for recombinant human granulocyte colony-stimulating factor. Application to a pharmacokinetic study in rats.", "content": "A competitive radioimmunoassay (RIA) and a sandwich enzyme-linked immunosorbent assay (ELISA) for the measurement of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rat serum was developed using polyclonal antibody obtained by immunizing rabbits with rhG-CSF. The anti-rhG-CSF antibody did not recognize other colony-stimulating factors or interleukins. RIA and ELISA gave satisfactory reproducibility as judged by intra- and inter-assay precision. Good agreements between the RIA, ELISA and bioassay were observed with rat serum samples after administration of rhG-CSF. The competitive RIA and sandwich ELISA described here appear to be as equally useful as the bioassay in studying the pharmacokinetics of rhG-CSF in animals.", "contents": "Development of a competitive radioimmunoassay and a sandwich enzyme-linked immunosorbent assay for recombinant human granulocyte colony-stimulating factor. Application to a pharmacokinetic study in rats. A competitive radioimmunoassay (RIA) and a sandwich enzyme-linked immunosorbent assay (ELISA) for the measurement of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rat serum was developed using polyclonal antibody obtained by immunizing rabbits with rhG-CSF. The anti-rhG-CSF antibody did not recognize other colony-stimulating factors or interleukins. RIA and ELISA gave satisfactory reproducibility as judged by intra- and inter-assay precision. Good agreements between the RIA, ELISA and bioassay were observed with rat serum samples after administration of rhG-CSF. The competitive RIA and sandwich ELISA described here appear to be as equally useful as the bioassay in studying the pharmacokinetics of rhG-CSF in animals."} {"id": "PMID:1280300", "title": "Gonadotropin-releasing hormone antagonists with N omega-triazolylornithine, -lysine, or -p-aminophenylalanine residues at positions 5 and 6.", "content": "In order to be used as fertility regulators in humans, gonadotropin releasing hormone (GnRH) antagonists must be extremely potent and long acting and exhibit negligible side effects such as stimulating histamine release. To this aim, we have recently synthesized a series of analogues with the standard Ac-DNal1-DCpa2-DPal3 substitutions, where the N omega-amino function of ornithine, lysine, or p-aminophenylalanine (Aph) was converted to the aminotriazolyl (atz) derivatives at positions 5 and 6 with further modifications at positions 7 and 10. The analogues were tested for their ability to bind to pituitary cell membranes, to release histamine in a mast cell assay, to inhibit luteinizing hormone (LH) secretion by castrated male rats or cultured pituitary cells, and to interfere with the ovulation in intact female rats. While the subcutaneous (sc) injection of 50 micrograms of Azaline A (7, [Ac-DNal1,DCpa2,DPal3,Lys5(atz),DLys6++ +(atz),ILys8,DAla10]GnRH) dissolved in 0.2 mL of an aqueous media significantly inhibited LH release in the castrated male rat for 24 h, the same dose of Azaline B (11), [Ac-DNal1,DCpa2,DPal3,Aph5(atz),DAph6++ +(atz),ILys8,DAla10]GnRH, inhibited LH release for 72 h. A similar long duration of action was observed for Antide ([Ac-DNal1,DCpa2,DPal3,Lys5(Nic),DLys6(Nic ),ILys8,DAla10]GnRH) but not for Nal-Glu ([Ac-DNal1,DCpa2,DPal3,Arg5,4-(pmethoxybenzoy l)-D-2-Abu6,DAla10]GnRH). In the same paradigm, a 5-fold dilution of the peptide (50 micrograms in 1 mL) and the use of three injection sites rather than one resulted in significantly shorter duration of action for most of the peptides tested. This suggested that long duration of action might be the result of slow release from the injection site(s). In order to investigate this possibility, Nal-Glu and Azaline B were injected intravenously (i.v.) at three doses (10, 50, 250 micrograms) to castrated male rats. At all doses, both peptides significantly lowered LH levels for 8 h. By 24 h, Nal-Glu (250 micrograms) and Azaline B (50 and 250 micrograms) still measurably inhibited LH secretion. Finally, only Azaline B (250 micrograms) was still active at 48 h. These findings demonstrate that subtle structural modifications will yield peptides with different half-lives after iv administration. These findings led us to investigate the effects of other structural modifications on duration of action. We observed that systematic substitutions at positions 7 (NMeLeu) and 10 (Pro9-NHEt, and Gly-NH2) were found to be deleterious. Of interest was the observation that only the DAla10-NH2 substitution led to long duration of action and enzymatic stability under the conditions tested.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Gonadotropin-releasing hormone antagonists with N omega-triazolylornithine, -lysine, or -p-aminophenylalanine residues at positions 5 and 6. In order to be used as fertility regulators in humans, gonadotropin releasing hormone (GnRH) antagonists must be extremely potent and long acting and exhibit negligible side effects such as stimulating histamine release. To this aim, we have recently synthesized a series of analogues with the standard Ac-DNal1-DCpa2-DPal3 substitutions, where the N omega-amino function of ornithine, lysine, or p-aminophenylalanine (Aph) was converted to the aminotriazolyl (atz) derivatives at positions 5 and 6 with further modifications at positions 7 and 10. The analogues were tested for their ability to bind to pituitary cell membranes, to release histamine in a mast cell assay, to inhibit luteinizing hormone (LH) secretion by castrated male rats or cultured pituitary cells, and to interfere with the ovulation in intact female rats. While the subcutaneous (sc) injection of 50 micrograms of Azaline A (7, [Ac-DNal1,DCpa2,DPal3,Lys5(atz),DLys6++ +(atz),ILys8,DAla10]GnRH) dissolved in 0.2 mL of an aqueous media significantly inhibited LH release in the castrated male rat for 24 h, the same dose of Azaline B (11), [Ac-DNal1,DCpa2,DPal3,Aph5(atz),DAph6++ +(atz),ILys8,DAla10]GnRH, inhibited LH release for 72 h. A similar long duration of action was observed for Antide ([Ac-DNal1,DCpa2,DPal3,Lys5(Nic),DLys6(Nic ),ILys8,DAla10]GnRH) but not for Nal-Glu ([Ac-DNal1,DCpa2,DPal3,Arg5,4-(pmethoxybenzoy l)-D-2-Abu6,DAla10]GnRH). In the same paradigm, a 5-fold dilution of the peptide (50 micrograms in 1 mL) and the use of three injection sites rather than one resulted in significantly shorter duration of action for most of the peptides tested. This suggested that long duration of action might be the result of slow release from the injection site(s). In order to investigate this possibility, Nal-Glu and Azaline B were injected intravenously (i.v.) at three doses (10, 50, 250 micrograms) to castrated male rats. At all doses, both peptides significantly lowered LH levels for 8 h. By 24 h, Nal-Glu (250 micrograms) and Azaline B (50 and 250 micrograms) still measurably inhibited LH secretion. Finally, only Azaline B (250 micrograms) was still active at 48 h. These findings demonstrate that subtle structural modifications will yield peptides with different half-lives after iv administration. These findings led us to investigate the effects of other structural modifications on duration of action. We observed that systematic substitutions at positions 7 (NMeLeu) and 10 (Pro9-NHEt, and Gly-NH2) were found to be deleterious. Of interest was the observation that only the DAla10-NH2 substitution led to long duration of action and enzymatic stability under the conditions tested.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1280301", "title": "Synthesis, absolute configuration, stereoselectivity, and receptor selectivity of (alpha R, beta S)-alpha,beta-dimethylhistamine, a novel high potent histamine H3 receptor agonist.", "content": "Depending on the selected synthetic pathway, structural variations of the neurotransmitter histamine led to mixtures of alpha,beta-dimethylhistamines as well as to the corresponding pure optical isomers. One of these isomers, namely (alpha R,beta S)-alpha,beta-dimethylhistamine, proved to be a highly potent H3 receptor agonist with exceptional receptor selectivity. The absolute configuration of the compound was determined by X-ray structure analysis of its dihydrobromide using the anomalous dispersion of bromine. The optical purity of both enantiomers of erythro-alpha,beta-dimethylhistamine was checked by 1HNMR investigations after acylation of the amines with (R)-2-methoxy-2-phenylacetyl chloride. As expected H3 receptors distinguish in a very strong way between the title compound and its alpha S,beta R-configured enantiomer. The agonistic potency of the latter is 2 orders of magnitude lower than the potency of (alpha R,beta S)-alpha,beta-dimethylhistamine.", "contents": "Synthesis, absolute configuration, stereoselectivity, and receptor selectivity of (alpha R, beta S)-alpha,beta-dimethylhistamine, a novel high potent histamine H3 receptor agonist. Depending on the selected synthetic pathway, structural variations of the neurotransmitter histamine led to mixtures of alpha,beta-dimethylhistamines as well as to the corresponding pure optical isomers. One of these isomers, namely (alpha R,beta S)-alpha,beta-dimethylhistamine, proved to be a highly potent H3 receptor agonist with exceptional receptor selectivity. The absolute configuration of the compound was determined by X-ray structure analysis of its dihydrobromide using the anomalous dispersion of bromine. The optical purity of both enantiomers of erythro-alpha,beta-dimethylhistamine was checked by 1HNMR investigations after acylation of the amines with (R)-2-methoxy-2-phenylacetyl chloride. As expected H3 receptors distinguish in a very strong way between the title compound and its alpha S,beta R-configured enantiomer. The agonistic potency of the latter is 2 orders of magnitude lower than the potency of (alpha R,beta S)-alpha,beta-dimethylhistamine."} {"id": "PMID:1280302", "title": "New algorithm to model protein-protein recognition based on surface complementarity. Applications to antibody-antigen docking.", "content": "A novel algorithm is presented which models protein-protein interactions using surface complementarity. The method is applied to antibody-antigen docking. A steric scoring scheme, based upon a soft potential, is used to assess complementarity, and a simple electrostatic model is then used to remove infeasible interactions. The soft potential allows for structural changes that occur during docking. Biochemical knowledge is necessary to reduce the number of docking orientations produced by the method to a manageable size. The information used includes the known epitope residues and a single loose distance constraint. The method is applied to all three crystallographically determined antibody-lysozyme complexes, HyHEL-10, D1.3 and HyHEL-5. For the first time, a predicted antibody structure (that of D1.3) is used as a docking target. In the four systems modelled, the method identifies between 15 and 40 possible docking orientations. The root-mean-square (r.m.s.) deviation between these orientations and the relevant crystallographic complex is measured in the interface region. For all four complexes an orientation is found with r.m.s. deviation in the range 1.9 A and 4.8 A. The algorithm is implemented on a single instruction/multiple datastream (SI/MD) architecture computer. The use of a parallel architecture computer ensures detailed coverage of the search space, whilst still maintaining a search time of two days.", "contents": "New algorithm to model protein-protein recognition based on surface complementarity. Applications to antibody-antigen docking. A novel algorithm is presented which models protein-protein interactions using surface complementarity. The method is applied to antibody-antigen docking. A steric scoring scheme, based upon a soft potential, is used to assess complementarity, and a simple electrostatic model is then used to remove infeasible interactions. The soft potential allows for structural changes that occur during docking. Biochemical knowledge is necessary to reduce the number of docking orientations produced by the method to a manageable size. The information used includes the known epitope residues and a single loose distance constraint. The method is applied to all three crystallographically determined antibody-lysozyme complexes, HyHEL-10, D1.3 and HyHEL-5. For the first time, a predicted antibody structure (that of D1.3) is used as a docking target. In the four systems modelled, the method identifies between 15 and 40 possible docking orientations. The root-mean-square (r.m.s.) deviation between these orientations and the relevant crystallographic complex is measured in the interface region. For all four complexes an orientation is found with r.m.s. deviation in the range 1.9 A and 4.8 A. The algorithm is implemented on a single instruction/multiple datastream (SI/MD) architecture computer. The use of a parallel architecture computer ensures detailed coverage of the search space, whilst still maintaining a search time of two days."} {"id": "PMID:1280303", "title": "[Cell staining for flow cytometry].", "content": "The innovation of biotechnology and computer technology makes it possible to give a quantitative analysis of cellular constituents and to evaluate cellular function accurately. Flow cytometry, which is one of such a new technology, coupled with successive developments of new fluorescence dyes greatly contributes to not only biological research fields but clinical medicine. This article reviews fluorochromes and cell staining with them for flow cytometry, focusing on the measurements of nuclear DNA content. Many of fluorescence dyes binds specifically to nucleic acid. Some of them intercalate double stoichiometrically stranded DNA and the illumination of an appropriate wavelength light excites the dyes, resulting in bright fluorescence proportional to the amount of DNA. However, it is necessary for flow cytometry to realize an optimal condition of nuclear staining with fluorochromes.", "contents": "[Cell staining for flow cytometry]. The innovation of biotechnology and computer technology makes it possible to give a quantitative analysis of cellular constituents and to evaluate cellular function accurately. Flow cytometry, which is one of such a new technology, coupled with successive developments of new fluorescence dyes greatly contributes to not only biological research fields but clinical medicine. This article reviews fluorochromes and cell staining with them for flow cytometry, focusing on the measurements of nuclear DNA content. Many of fluorescence dyes binds specifically to nucleic acid. Some of them intercalate double stoichiometrically stranded DNA and the illumination of an appropriate wavelength light excites the dyes, resulting in bright fluorescence proportional to the amount of DNA. However, it is necessary for flow cytometry to realize an optimal condition of nuclear staining with fluorochromes."} {"id": "PMID:1280304", "title": "[Application of bromodeoxyuridine (BrdU) and anti-BrdU monoclonal antibody for the analysis of tumor cell kinetics by flow cytometry].", "content": "Bromodeoxyuridine (BrdU) is a thymidine analogue which is incorporated into the cells of DNA synthetic phase. BrdU-labeling index (BrdU-LI) of tumor cells can be estimated with an anti-BrdU antibody. Bivariate distributions of BrdU and DNA content are simultaneously obtained by flow cytometric two parameter analysis with a double staining method. The exact DNA synthetic cells are determined using this method by removal of the cells having S phase DNA content without DNA synthesis; quiescent (S0) cells. Once the BrdU-LIs are obtained, DNA synthesis time (Ts) and other time parameters of tumor cell kinetics can be calculated by mathematical methods. BrdU and anti-BrdU monoclonal antibody makes it possible to easily and rapidly recognize the tumor cell kinetics with high accuracy.", "contents": "[Application of bromodeoxyuridine (BrdU) and anti-BrdU monoclonal antibody for the analysis of tumor cell kinetics by flow cytometry]. Bromodeoxyuridine (BrdU) is a thymidine analogue which is incorporated into the cells of DNA synthetic phase. BrdU-labeling index (BrdU-LI) of tumor cells can be estimated with an anti-BrdU antibody. Bivariate distributions of BrdU and DNA content are simultaneously obtained by flow cytometric two parameter analysis with a double staining method. The exact DNA synthetic cells are determined using this method by removal of the cells having S phase DNA content without DNA synthesis; quiescent (S0) cells. Once the BrdU-LIs are obtained, DNA synthesis time (Ts) and other time parameters of tumor cell kinetics can be calculated by mathematical methods. BrdU and anti-BrdU monoclonal antibody makes it possible to easily and rapidly recognize the tumor cell kinetics with high accuracy."} {"id": "PMID:1280305", "title": "[Flow cytometric analysis of Ki-67 reactive antigen].", "content": "Monoclonal antibody Ki-67 is a useful and easy means for evaluating cell proliferative activity. Furthermore, it appears to provide valuable prognostic informations in some neoplastic diseases. However, almost all studies on solid tumors were performed only by microscopic observation using immunohistochemistry, and not by flow cytometry. Therefore, the information deduced from the findings is limited. The method of DNA/Ki-67 double staining of solid tissue and cultured cells for flow cytometry is shown, and the significance and the usefulness of flow cytometric study of Ki-67 in clinical use are discussed.", "contents": "[Flow cytometric analysis of Ki-67 reactive antigen]. Monoclonal antibody Ki-67 is a useful and easy means for evaluating cell proliferative activity. Furthermore, it appears to provide valuable prognostic informations in some neoplastic diseases. However, almost all studies on solid tumors were performed only by microscopic observation using immunohistochemistry, and not by flow cytometry. Therefore, the information deduced from the findings is limited. The method of DNA/Ki-67 double staining of solid tissue and cultured cells for flow cytometry is shown, and the significance and the usefulness of flow cytometric study of Ki-67 in clinical use are discussed."} {"id": "PMID:1280306", "title": "[Flow cytometric BrdU/DNA assay for anticancer agent sensitivity test].", "content": "The significance of BrdU/DNA double staining method using flow cytometry as a chemosensitivity test of anticancer agents is herein reported. Experimentally, CDDP, ADM and MMC yielded a significant increase of G2 phase fraction at 24, 48 and 72 hours, and caused a significant decrease of BrdU labeling index at 48 hours. The changes of G2 phase fraction and BrdU labeling index were correlated well with the result of colony forming test, and, therefore, were considered as a useful index of lethal effect of anticancer agents. For the clinical application, enzymatic preparation and discontinuous Ficoll density gradient method might be advantageous to collect viable tumor cells from solid specimen. Flow cytometric BrdU/DNA assay can be clinically applied as a chemosensitivity test in selecting effective anticancer drugs.", "contents": "[Flow cytometric BrdU/DNA assay for anticancer agent sensitivity test]. The significance of BrdU/DNA double staining method using flow cytometry as a chemosensitivity test of anticancer agents is herein reported. Experimentally, CDDP, ADM and MMC yielded a significant increase of G2 phase fraction at 24, 48 and 72 hours, and caused a significant decrease of BrdU labeling index at 48 hours. The changes of G2 phase fraction and BrdU labeling index were correlated well with the result of colony forming test, and, therefore, were considered as a useful index of lethal effect of anticancer agents. For the clinical application, enzymatic preparation and discontinuous Ficoll density gradient method might be advantageous to collect viable tumor cells from solid specimen. Flow cytometric BrdU/DNA assay can be clinically applied as a chemosensitivity test in selecting effective anticancer drugs."} {"id": "PMID:1280307", "title": "[Development of a new supplementary diagnostic method for endometrial cancer by flow cytometry employing anti-endometrial cancer antibody, MSN-1 and MSN-3].", "content": "In cytology, it is often difficult to make a definite diagnosis of endometrial cancer. In order to devise a new supplementary method, using flow cytometry we analyzed the reactivities of endometrial cells with two monoclonal antibodies (MSN-1 and MSN-3), both of which are strongly reactive to endometrial cancer cells. Employing either or both antibodies in flow cytometry, we investigated the usefulness of this analysis for distinguishing endometrial cancer cells from normal endometrial cells. Results revealed a low positive rate for normal endometrium: 9.2% with MSN-1 and 5.0% with MSN-3. In contrast, for endometrial cancer the positive rate was high: 81.2% with MSN-1 and 43.8% with MSN-3. Combined analysis with both antibodies increased the positive rate for endometrial cancer to 93.7%. These results suggest that analysis by flow cytometry employing MSN-1 and MSN-3 may have a diagnostic value for endometrial cancer. We are also investigating the usefulness of two-color analysis using these antibodies.", "contents": "[Development of a new supplementary diagnostic method for endometrial cancer by flow cytometry employing anti-endometrial cancer antibody, MSN-1 and MSN-3]. In cytology, it is often difficult to make a definite diagnosis of endometrial cancer. In order to devise a new supplementary method, using flow cytometry we analyzed the reactivities of endometrial cells with two monoclonal antibodies (MSN-1 and MSN-3), both of which are strongly reactive to endometrial cancer cells. Employing either or both antibodies in flow cytometry, we investigated the usefulness of this analysis for distinguishing endometrial cancer cells from normal endometrial cells. Results revealed a low positive rate for normal endometrium: 9.2% with MSN-1 and 5.0% with MSN-3. In contrast, for endometrial cancer the positive rate was high: 81.2% with MSN-1 and 43.8% with MSN-3. Combined analysis with both antibodies increased the positive rate for endometrial cancer to 93.7%. These results suggest that analysis by flow cytometry employing MSN-1 and MSN-3 may have a diagnostic value for endometrial cancer. We are also investigating the usefulness of two-color analysis using these antibodies."} {"id": "PMID:1280308", "title": "[The affinity lavage of the abdominal cavity in diffuse peritonitis with liquid sorbents based on cross-linked dextrans].", "content": "Experiments were conducted on 35 Wistar rats with generalized purulent peritonitis. Twenty-four hours after infection the authors introduced into the animals' abdominal cavity gels of cross-linked dextrans with immobilized polymixin (50 mg/g dry weight) and terrilithin (100 PE/g dry weight), as well as a combination of these sorbents with 24-hour exposure in a 5 ml volume. The object of the study was the detoxification effect. The authors revealed a phenomenon of agglutination of red cells of an ox or rat sensitized by plasma of sick animals in mixing with sephadex G-200 granules with polymixin W immobilized on them. The agglutination titers determined the activity of the sorbent taking part in lavage of the abdominal cavity. The study showed that cross-linked dextrans with immobilized polymixin B and terrilithin introduced into the abdominal cavity in peritonitis are capable of extracting substrates possessing affinity to them, the polymixin sorbent raises the quality of careful mechanical lavage. Combination of gels based on cross-linked dextrans with enzymatic and affinity functions in relation to toxins leads to detoxification and restoration of the disturbed biochemical values by 87%.", "contents": "[The affinity lavage of the abdominal cavity in diffuse peritonitis with liquid sorbents based on cross-linked dextrans]. Experiments were conducted on 35 Wistar rats with generalized purulent peritonitis. Twenty-four hours after infection the authors introduced into the animals' abdominal cavity gels of cross-linked dextrans with immobilized polymixin (50 mg/g dry weight) and terrilithin (100 PE/g dry weight), as well as a combination of these sorbents with 24-hour exposure in a 5 ml volume. The object of the study was the detoxification effect. The authors revealed a phenomenon of agglutination of red cells of an ox or rat sensitized by plasma of sick animals in mixing with sephadex G-200 granules with polymixin W immobilized on them. The agglutination titers determined the activity of the sorbent taking part in lavage of the abdominal cavity. The study showed that cross-linked dextrans with immobilized polymixin B and terrilithin introduced into the abdominal cavity in peritonitis are capable of extracting substrates possessing affinity to them, the polymixin sorbent raises the quality of careful mechanical lavage. Combination of gels based on cross-linked dextrans with enzymatic and affinity functions in relation to toxins leads to detoxification and restoration of the disturbed biochemical values by 87%."} {"id": "PMID:1280309", "title": "Intelligibility assessment in developmental phonological disorders: accuracy of caregiver gloss.", "content": "Fifteen caregivers each glossed a simultaneously videotaped and audiotaped sample of their child with speech delay engaged in conversation with a clinician. One of the authors generated a reference gloss for each sample, aided by (a) prior knowledge of the child's speech-language status and error patterns, (b) glosses from the child's clinician and the child's caregiver, (c) unlimited replays of the taped sample, and (d) the information gained from completing a narrow phonetic transcription of the sample. Caregivers glossed an average of 78% of the utterances and 81% of the words. A comparison of their glosses to the reference glosses suggested that they accurately understood an average of 58% of the utterances and 73% of the words. Discussion considers the implications of such findings for methodological and theoretical issues underlying children's moment-to-moment intelligibility breakdowns during speech-language processing.", "contents": "Intelligibility assessment in developmental phonological disorders: accuracy of caregiver gloss. Fifteen caregivers each glossed a simultaneously videotaped and audiotaped sample of their child with speech delay engaged in conversation with a clinician. One of the authors generated a reference gloss for each sample, aided by (a) prior knowledge of the child's speech-language status and error patterns, (b) glosses from the child's clinician and the child's caregiver, (c) unlimited replays of the taped sample, and (d) the information gained from completing a narrow phonetic transcription of the sample. Caregivers glossed an average of 78% of the utterances and 81% of the words. A comparison of their glosses to the reference glosses suggested that they accurately understood an average of 58% of the utterances and 73% of the words. Discussion considers the implications of such findings for methodological and theoretical issues underlying children's moment-to-moment intelligibility breakdowns during speech-language processing."} {"id": "PMID:1280310", "title": "A 28-year follow-up of adults with a history of moderate phonological disorder: linguistic and personality results.", "content": "The present investigation is a follow-up to a longitudinal speech and academic study involving approximately 400 normally developing children begun in 1960 by Mildred Templin. From this large data base, the present project invited the participation of two groups of subjects (now aged 32 to 34): (a) 24 adults with a documented history of moderately severe phonological disorder that persisted at least through the end of first grade (probands) and (b) 28 adults from the same birth cohort and schools who were known to have had at least average articulation skills over the same period (controls). Results of follow-up testing revealed that the proband adults performed significantly more poorly than the control adults on all of the administered measures of articulation, expressive language, and receptive language. Results obtained from a screening of nonverbal reasoning ability were equivocal. On a questionnaire measure of personality, both groups scored well within the normal range for the dimensions of extroversion and neuroticism when compared to the test's normative sample. These results have been interpreted as suggesting that although many adults with a childhood history of delayed phonological development will continue to experience linguistic outcomes that are less favorable than those of controls, their performance in selected nonlanguage domains (e.g., nonverbal reasoning, personality) will be far more typical of the general population.", "contents": "A 28-year follow-up of adults with a history of moderate phonological disorder: linguistic and personality results. The present investigation is a follow-up to a longitudinal speech and academic study involving approximately 400 normally developing children begun in 1960 by Mildred Templin. From this large data base, the present project invited the participation of two groups of subjects (now aged 32 to 34): (a) 24 adults with a documented history of moderately severe phonological disorder that persisted at least through the end of first grade (probands) and (b) 28 adults from the same birth cohort and schools who were known to have had at least average articulation skills over the same period (controls). Results of follow-up testing revealed that the proband adults performed significantly more poorly than the control adults on all of the administered measures of articulation, expressive language, and receptive language. Results obtained from a screening of nonverbal reasoning ability were equivocal. On a questionnaire measure of personality, both groups scored well within the normal range for the dimensions of extroversion and neuroticism when compared to the test's normative sample. These results have been interpreted as suggesting that although many adults with a childhood history of delayed phonological development will continue to experience linguistic outcomes that are less favorable than those of controls, their performance in selected nonlanguage domains (e.g., nonverbal reasoning, personality) will be far more typical of the general population."} {"id": "PMID:1280311", "title": "[Polymorphism MI detected through the enzyme MspI in the study of congenital protein C deficiency].", "content": "In order to find alternatives for the diagnosis of hereditary protein C (PC) deficiency, we have studied the diagnostic informativity of the restriction fragment length polymorphism (RFLP) MI, located 7 kb upstream of the PC gene and detected with the restriction enzyme MspI. The RFLP MI has been analysed in 77 individuals belonging to 27 families with congenital PC deficiency, as well as in a control group of 46 healthy donors. The analysis has been performed by PCR amplification and MspI digestion of the polymorphic DNA fragment. The allelic frequencies of the RFLP MI in the population studied are 0.69 for the allele A1, without the MspI restriction site, and 0.31 for the allele A2, with the MspI site. No differences have been found between the control and the PC deficient groups. The informativity of the polymorphism has been calculated to be 33.8%. Consegregation studies between this RFLP and PC deficiency have allowed the determination of the allele associated to the polymorphism in 21 out of the 27 studied families. Furthermore, an asymptomatic PC deficient carrier, with normal PC levels, has been identified. The study of this RFLP in families with hereditary PC deficiency may be useful for the identification of PC deficient carriers as well as for the prenatal diagnosis of the deficiency.", "contents": "[Polymorphism MI detected through the enzyme MspI in the study of congenital protein C deficiency]. In order to find alternatives for the diagnosis of hereditary protein C (PC) deficiency, we have studied the diagnostic informativity of the restriction fragment length polymorphism (RFLP) MI, located 7 kb upstream of the PC gene and detected with the restriction enzyme MspI. The RFLP MI has been analysed in 77 individuals belonging to 27 families with congenital PC deficiency, as well as in a control group of 46 healthy donors. The analysis has been performed by PCR amplification and MspI digestion of the polymorphic DNA fragment. The allelic frequencies of the RFLP MI in the population studied are 0.69 for the allele A1, without the MspI restriction site, and 0.31 for the allele A2, with the MspI site. No differences have been found between the control and the PC deficient groups. The informativity of the polymorphism has been calculated to be 33.8%. Consegregation studies between this RFLP and PC deficiency have allowed the determination of the allele associated to the polymorphism in 21 out of the 27 studied families. Furthermore, an asymptomatic PC deficient carrier, with normal PC levels, has been identified. The study of this RFLP in families with hereditary PC deficiency may be useful for the identification of PC deficient carriers as well as for the prenatal diagnosis of the deficiency."} {"id": "PMID:1280313", "title": "The use of radioactively labelled riboprobes for in situ hybridization: background and examples of application.", "content": "An overview is provided concerning the preparation and use of radiolabelled single-stranded RNA probes (riboprobes) for in situ hybridization. All theoretical aspects are covered as well as some practical examples from the authors' experience. The use of riboprobes for in situ hybridization represents a valid and highly sensitive alternative to oligonucleotide probes. A sample protocol is finally described in detail: this should enable any investigators to design the ISH assay that best fits their particular needs.", "contents": "The use of radioactively labelled riboprobes for in situ hybridization: background and examples of application. An overview is provided concerning the preparation and use of radiolabelled single-stranded RNA probes (riboprobes) for in situ hybridization. All theoretical aspects are covered as well as some practical examples from the authors' experience. The use of riboprobes for in situ hybridization represents a valid and highly sensitive alternative to oligonucleotide probes. A sample protocol is finally described in detail: this should enable any investigators to design the ISH assay that best fits their particular needs."} {"id": "PMID:1280314", "title": "Hepatitis B virus, alpha-fetoprotein synthesis, and hepatocellular carcinoma in Zaire.", "content": "We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966-1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 +/- 17.5 years) and females (37.40 +/- 15.16 years) was significantly different (p < 0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96% vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumourous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (> 20 ng/ml) in 90% of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19,322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102,565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95% CI: [182.8, 19,952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade.", "contents": "Hepatitis B virus, alpha-fetoprotein synthesis, and hepatocellular carcinoma in Zaire. We investigated the epidemiology of hepatocellular carcinoma (HCC) in Zaire, and evaluated the association between exposure to hepatitis B virus (HBV) and the development of HCC. Two hundred and twenty-three consecutive cases of HCC diagnosed over 19 years (1966-1985) were reviewed. HCC represented 8.32% of all carcinomas and 5.56% of all cancers. Frequency was higher in males (75.7%) than in females (24.3%); a sex ratio of 3/1. The majority (82.1%) of patients were aged 14 to 55 years with a peak occurrence in the fourth decade (28.6%). The mean age in males (41.27 +/- 17.5 years) and females (37.40 +/- 15.16 years) was significantly different (p < 0.02). Sera from 40 patients and 68 age and sex-matched controls were analyzed for markers of HBV infection: patients and controls had comparable rates of exposure (96% vs 72.1%, respectively). However, patients had significantly higher HBsAg carrier rates (56.7% vs 7.35%; p < 0.001), and lower anti-HBsAg seroconversion rates (25% vs 63.2%, p < 0.05). Using immunohistochemical analysis, the livers of patients were evaluated for HBsAg and HBcAg. These HBV antigens were more frequent in non-tumourous hepatocytes (53.3% vs 23.3%, respectively) than in HCC cells (13.3% vs 3.3%). Serum alpha-fetoprotein (AFP) was abnormal (> 20 ng/ml) in 90% of patients. The geometric mean (GM) AFP was 7273.8 ng/ml. AFP levels were significantly higher in HBsAg-positive HCC cases (GM: 19,322.6 ng/ml; 95% confidence interval (CI): [3639.2, 102,565.2]) than in antigen negative cases (GM: 1939.5 ng/ml; 95% CI: [182.8, 19,952.6]), but did not correlate with HBV replication. Immunohistochemical detection of AFP revealed a similar correlation between AFP and HBsAg. Neither AFP level nor HBsAg production correlated with cellular atypia or tumor grade."} {"id": "PMID:1280315", "title": "Glutathione treatment of hepatocellular carcinoma.", "content": "This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH daily from the time of diagnosis. Two patients withdrew shortly after receiving GSH due to intolerable side-effects. Of the six eligible patients, two had mildly advanced tumors and four moderately advanced tumors. At 1-2-month intervals the liver was CT and ultra-sound scanned to assess the growth status of the tumor (progression, stagnation or regression). All the patients, except a male with a fibrolamellar type of HCC, died within 1 year after diagnosis. Two women with moderately advanced tumors survived almost 1 year, tumor growth stopped or regressed and in one of the women an initially abnormal alfa-1-fetoprotein (AFP) returned to normal after GSH treatment. AFP remained normal throughout the treatment period in the other women. These observations indicate that GSH may have a sex-dependent effect on HCC. However, further studies involving more patients are required to pursue this hypothesis.", "contents": "Glutathione treatment of hepatocellular carcinoma. This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH daily from the time of diagnosis. Two patients withdrew shortly after receiving GSH due to intolerable side-effects. Of the six eligible patients, two had mildly advanced tumors and four moderately advanced tumors. At 1-2-month intervals the liver was CT and ultra-sound scanned to assess the growth status of the tumor (progression, stagnation or regression). All the patients, except a male with a fibrolamellar type of HCC, died within 1 year after diagnosis. Two women with moderately advanced tumors survived almost 1 year, tumor growth stopped or regressed and in one of the women an initially abnormal alfa-1-fetoprotein (AFP) returned to normal after GSH treatment. AFP remained normal throughout the treatment period in the other women. These observations indicate that GSH may have a sex-dependent effect on HCC. However, further studies involving more patients are required to pursue this hypothesis."} {"id": "PMID:1280316", "title": "Construction of chimaeric genes for mapping a surface-exposed epitope on the pilus of non-typable Haemophilus influenzae strain M37.", "content": "A murine monoclonal antibody (mAb), designated 3H12, reacts with a surface-exposed conformational epitope on the pilus of non-typable Haemophilus influenzae strain M37. This antibody does not recognize the related pilus from H. influenzae type b, strain MinnA. Although mAb 3H12 does not recognize strain M37 pilin on Western blots, mAb 3H12 recognizes the recombinant M37 pilin protein expressed by Escherichia coli. In order to map the epitope recognized by mAb 3H12, we constructed a series of chimaeric genes. The chimaeric genes were expressed in E. coli and the chimaeric proteins characterized with respect to their reactivity with mAb 3H12. Residues between 37 and 100 of the M37 pilin protein are essential for the expression of the mAb 3H12 epitope. Residues in the carboxyl half of the M37 protein enhance the reactivity of mAb 3H12 when expressed in the presence of residues 37-100. Construction of chimaeric genes may provide a general methodology for mapping of conformational epitopes expressed by one of a related pair of proteins.", "contents": "Construction of chimaeric genes for mapping a surface-exposed epitope on the pilus of non-typable Haemophilus influenzae strain M37. A murine monoclonal antibody (mAb), designated 3H12, reacts with a surface-exposed conformational epitope on the pilus of non-typable Haemophilus influenzae strain M37. This antibody does not recognize the related pilus from H. influenzae type b, strain MinnA. Although mAb 3H12 does not recognize strain M37 pilin on Western blots, mAb 3H12 recognizes the recombinant M37 pilin protein expressed by Escherichia coli. In order to map the epitope recognized by mAb 3H12, we constructed a series of chimaeric genes. The chimaeric genes were expressed in E. coli and the chimaeric proteins characterized with respect to their reactivity with mAb 3H12. Residues between 37 and 100 of the M37 pilin protein are essential for the expression of the mAb 3H12 epitope. Residues in the carboxyl half of the M37 protein enhance the reactivity of mAb 3H12 when expressed in the presence of residues 37-100. Construction of chimaeric genes may provide a general methodology for mapping of conformational epitopes expressed by one of a related pair of proteins."} {"id": "PMID:1280317", "title": "Antibodies to N-terminal peptides of gonococcal porin are bactericidal when gonococcal lipopolysaccharide is not sialylated.", "content": "Six synthetic 25-mer peptides corresponding to certain presumed surface-exposed regions of gonococcal porin protein I (PI) were made from strains FA19 (PIA) and MS11 (PIB). Four peptides were immunogenic in rabbits. Affinity-purified antisera against both PIA and PIB N-terminal peptides were bactericidal for homologous gonococci and many heterologous PI serovars. However, sialylation of gonococcal lipopolysaccharide (LPS) by growth of gonococci in the presence of cytidine monophosphate-neuraminic acid (CMP-NANA) abrogated the bactericidal activity of these antisera. Binding of anti-PI monoclonal antibodies to whole gonococci was reduced two- to fourfold by sialylation of LPS, suggesting that sialylation may inhibit bactericidal activity by masking porin epitopes. However, binding of anti-PII (Opa) monoclonal antibodies was not inhibited, yet complement-mediated killing was inhibited by sialylated LPS. Binding of complement components C3 and C9 was inhibited in the presence of either anti-PI or anti-PII monoclonals when gonococci were grown in the presence of CMP-NANA. Thus sialylation inhibited both anti-PI antibody binding and complement deposition, with a resultant decrease in bactericidal activity.", "contents": "Antibodies to N-terminal peptides of gonococcal porin are bactericidal when gonococcal lipopolysaccharide is not sialylated. Six synthetic 25-mer peptides corresponding to certain presumed surface-exposed regions of gonococcal porin protein I (PI) were made from strains FA19 (PIA) and MS11 (PIB). Four peptides were immunogenic in rabbits. Affinity-purified antisera against both PIA and PIB N-terminal peptides were bactericidal for homologous gonococci and many heterologous PI serovars. However, sialylation of gonococcal lipopolysaccharide (LPS) by growth of gonococci in the presence of cytidine monophosphate-neuraminic acid (CMP-NANA) abrogated the bactericidal activity of these antisera. Binding of anti-PI monoclonal antibodies to whole gonococci was reduced two- to fourfold by sialylation of LPS, suggesting that sialylation may inhibit bactericidal activity by masking porin epitopes. However, binding of anti-PII (Opa) monoclonal antibodies was not inhibited, yet complement-mediated killing was inhibited by sialylated LPS. Binding of complement components C3 and C9 was inhibited in the presence of either anti-PI or anti-PII monoclonals when gonococci were grown in the presence of CMP-NANA. Thus sialylation inhibited both anti-PI antibody binding and complement deposition, with a resultant decrease in bactericidal activity."} {"id": "PMID:1280319", "title": "[Prognostic factors in patients with invasive differentiated thyroid carcinoma who underwent palliative resection].", "content": "In order to determine surgical strategy for locally advanced thyroid carcinoma, a multivariate analysis of prognostic factors was carried out with 70 patients of locally advanced thyroid carcinoma who underwent palliative surgery. Multivariate analysis was conducted by Cox's proportional hazard model. The patients have been followed up from 5 to 26 years. We have demonstrated the influence of age, sex, distant metastasis, pathological findings, numbers of adjacent organs, infiltrated, extent of resection, external irradiation and 131I therapy on survival. The result of this study showed that age had an impact on survival. The survival rate of the patients under 40 years was much better than that of the patients 40 years and over. The result implies that aggressive surgery and postoperative adjuvant therapy should be considered in the old patients, but not always be indication in the young patients.", "contents": "[Prognostic factors in patients with invasive differentiated thyroid carcinoma who underwent palliative resection]. In order to determine surgical strategy for locally advanced thyroid carcinoma, a multivariate analysis of prognostic factors was carried out with 70 patients of locally advanced thyroid carcinoma who underwent palliative surgery. Multivariate analysis was conducted by Cox's proportional hazard model. The patients have been followed up from 5 to 26 years. We have demonstrated the influence of age, sex, distant metastasis, pathological findings, numbers of adjacent organs, infiltrated, extent of resection, external irradiation and 131I therapy on survival. The result of this study showed that age had an impact on survival. The survival rate of the patients under 40 years was much better than that of the patients 40 years and over. The result implies that aggressive surgery and postoperative adjuvant therapy should be considered in the old patients, but not always be indication in the young patients."} {"id": "PMID:1280320", "title": "Identification of G-proteins in rat parotid gland plasma membranes and granule membranes: presence of distinct components in granule membranes.", "content": "We have identified by immunoblotting and ADP-ribosylation by cholera toxin and pertussis toxin the presence of Mr 43 and 46 KDa Gs alpha, and 39 and 41 KDa Gi alpha subunits in rat parotid gland plasma membranes but not in granule membranes. A Mr 28 KDa polypeptide that served as substrate for ADP-ribosylation by both cholera toxin and pertussis toxin was present exclusively in granule membranes. Photoaffinity crosslinking of [alpha-32P]GTP showed the presence of high molecular weight GTP-binding proteins (Mr 160, 100 KDa) in granule membranes. Six low molecular weight GTP-binding proteins (Mr 21-28 KDa) were differentially distributed in both plasma membranes and granule membranes. The present study identifies various GTP-binding proteins in rat parotid gland plasma membranes and granule membranes, and demonstrates the presence of distinct molecular weight GTP-binding proteins in granule membranes. These granule-associated GTP-binding proteins may be involved in secretory processes.", "contents": "Identification of G-proteins in rat parotid gland plasma membranes and granule membranes: presence of distinct components in granule membranes. We have identified by immunoblotting and ADP-ribosylation by cholera toxin and pertussis toxin the presence of Mr 43 and 46 KDa Gs alpha, and 39 and 41 KDa Gi alpha subunits in rat parotid gland plasma membranes but not in granule membranes. A Mr 28 KDa polypeptide that served as substrate for ADP-ribosylation by both cholera toxin and pertussis toxin was present exclusively in granule membranes. Photoaffinity crosslinking of [alpha-32P]GTP showed the presence of high molecular weight GTP-binding proteins (Mr 160, 100 KDa) in granule membranes. Six low molecular weight GTP-binding proteins (Mr 21-28 KDa) were differentially distributed in both plasma membranes and granule membranes. The present study identifies various GTP-binding proteins in rat parotid gland plasma membranes and granule membranes, and demonstrates the presence of distinct molecular weight GTP-binding proteins in granule membranes. These granule-associated GTP-binding proteins may be involved in secretory processes."} {"id": "PMID:1280321", "title": "Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation.", "content": "The 130 kDa atrial natriuretic factor receptor (ANF-R1) purified from bovine adrenal zona glomerulosa is phosphorylated in vitro by serine/threonine protein kinases such as cAMP-, cGMP-dependent and protein kinase C. This phosphorylation is independent of the presence of ANF (99-126) and there is no detectable intrinsic kinase activity associated with the ANF-R1 receptor or with its activated form. In bovine adrenal zona glomerulosa cells, TPA (phorbol ester) induces a marked inhibition of the ANF-stimulated cGMP accumulation as well as of the membrane ANF-sensitive guanylate cyclase catalytic activity without any change in the binding capacity or affinity for 125I-ANF. However, we have demonstrated a significant 32P incorporation in the ANF-R1 receptor of the TPA-treated cells. The effect of TPA on the zona glomerulosa ANF-R1 receptors was abolished by calphostin C, a specific protein kinase C inhibitor. Altered ANF actions due to blunted response of guanylate cyclase to ANF could be a consequence of the ANF receptor phosphorylation by excessive activity of protein kinase C and might be involved in the pathogenesis of hypertension.", "contents": "Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation. The 130 kDa atrial natriuretic factor receptor (ANF-R1) purified from bovine adrenal zona glomerulosa is phosphorylated in vitro by serine/threonine protein kinases such as cAMP-, cGMP-dependent and protein kinase C. This phosphorylation is independent of the presence of ANF (99-126) and there is no detectable intrinsic kinase activity associated with the ANF-R1 receptor or with its activated form. In bovine adrenal zona glomerulosa cells, TPA (phorbol ester) induces a marked inhibition of the ANF-stimulated cGMP accumulation as well as of the membrane ANF-sensitive guanylate cyclase catalytic activity without any change in the binding capacity or affinity for 125I-ANF. However, we have demonstrated a significant 32P incorporation in the ANF-R1 receptor of the TPA-treated cells. The effect of TPA on the zona glomerulosa ANF-R1 receptors was abolished by calphostin C, a specific protein kinase C inhibitor. Altered ANF actions due to blunted response of guanylate cyclase to ANF could be a consequence of the ANF receptor phosphorylation by excessive activity of protein kinase C and might be involved in the pathogenesis of hypertension."} {"id": "PMID:1280322", "title": "cis-acting sequences involved in exon selection in the chicken beta-tropomyosin gene.", "content": "The chicken beta-tropomyosin gene contains an internal pair of mutually exclusive exons (6A and 6B) that are selected in a tissue-specific manner. Exon 6A is incorporated in fibroblasts and smooth muscle cells, whereas exon 6B is skeletal muscle specific. In this study we show that two different regions in the intron between the two mutually exclusive exons are important for this specific selection in nonmuscle cells. Sequences in the 3' end of the intron have a negative effect in the recognition of the 3' splice site, while sequences in the 5' end of the intron have a positive effect in the recognition of the 5' splice site. First, sequences in exon 6B as well as in the intron upstream of exon 6B are both able to inhibit splicing when placed in a heterologous gene. The sequences in the polypyrimidine stretch region contribute to splicing inhibition of exons 5 or 6A to 6B through a mechanism independent of their implication in the previously described secondary structure around exon 6B. Second, we have identified a sequence of 30 nucleotides in the intron just downstream of exon 6A that is essential for the recognition of the 5' splice site of exon 6A. This is so even after introduction of a consensus sequence into the 5' splice site of this exon. Deletion of this sequence blocks splicing of exon 6A to 6B after formation of the presplicing complex. Taken together, these results suggest that both the mutually exclusive behavior and the choice between exons 6A and 6B of the chicken beta-tropomyosin gene are trans regulated.", "contents": "cis-acting sequences involved in exon selection in the chicken beta-tropomyosin gene. The chicken beta-tropomyosin gene contains an internal pair of mutually exclusive exons (6A and 6B) that are selected in a tissue-specific manner. Exon 6A is incorporated in fibroblasts and smooth muscle cells, whereas exon 6B is skeletal muscle specific. In this study we show that two different regions in the intron between the two mutually exclusive exons are important for this specific selection in nonmuscle cells. Sequences in the 3' end of the intron have a negative effect in the recognition of the 3' splice site, while sequences in the 5' end of the intron have a positive effect in the recognition of the 5' splice site. First, sequences in exon 6B as well as in the intron upstream of exon 6B are both able to inhibit splicing when placed in a heterologous gene. The sequences in the polypyrimidine stretch region contribute to splicing inhibition of exons 5 or 6A to 6B through a mechanism independent of their implication in the previously described secondary structure around exon 6B. Second, we have identified a sequence of 30 nucleotides in the intron just downstream of exon 6A that is essential for the recognition of the 5' splice site of exon 6A. This is so even after introduction of a consensus sequence into the 5' splice site of this exon. Deletion of this sequence blocks splicing of exon 6A to 6B after formation of the presplicing complex. Taken together, these results suggest that both the mutually exclusive behavior and the choice between exons 6A and 6B of the chicken beta-tropomyosin gene are trans regulated."} {"id": "PMID:1280323", "title": "Biochemical and cytological changes associated with expression of deregulated pp60src in Xenopus oocytes.", "content": "We have examined the effects of Xenopus pp60c-src with constitutive kinase activity on the morphology and maturation of Xenopus laevis oocytes. When RNA encoding this deregulated variant was injected into stage VI oocytes, we observed a gross alteration in the cortex of the oocyte. This alteration involved aggregation of pigment and invagination of the cortex in a large area proximal to the site of injection. This phenomenon was not seen in oocytes injected with RNA encoding wild-type pp60c-src. We have correlated this phenomenon with the tyrosine phosphorylation of 84- and 100-kDa proteins. These phosphorylated proteins colocalized with the alteration in the oocyte cortex when assayed by both biochemical and immunocytochemical methods. Neither the pigment aggregation nor phosphorylation of the 84- and 100-kDa proteins was observed in oocytes expressing a nonmyristoylated version of the deregulated pp60c-src. Expression of deregulated Xenopus fyn, a src-family member, resulted in a phenotype similar to that seen with deregulated src. However, in the fyn-injected oocytes, many more proteins were phosphorylated on tyrosine than in the src-injected oocytes. Progesterone stimulation of oocytes expressing deregulated pp60c-src resulted in an increase in the number of tyrosine-phosphorylated proteins. This change may represent the response of pp60src to the resumption of the cell cycle in maturing oocytes. These data suggest that the oocyte may be a particularly useful system for investigating the role of pp60c-src in the regulation of cytoskeletal structure and in the regulation of events associated with the cell cycle.", "contents": "Biochemical and cytological changes associated with expression of deregulated pp60src in Xenopus oocytes. We have examined the effects of Xenopus pp60c-src with constitutive kinase activity on the morphology and maturation of Xenopus laevis oocytes. When RNA encoding this deregulated variant was injected into stage VI oocytes, we observed a gross alteration in the cortex of the oocyte. This alteration involved aggregation of pigment and invagination of the cortex in a large area proximal to the site of injection. This phenomenon was not seen in oocytes injected with RNA encoding wild-type pp60c-src. We have correlated this phenomenon with the tyrosine phosphorylation of 84- and 100-kDa proteins. These phosphorylated proteins colocalized with the alteration in the oocyte cortex when assayed by both biochemical and immunocytochemical methods. Neither the pigment aggregation nor phosphorylation of the 84- and 100-kDa proteins was observed in oocytes expressing a nonmyristoylated version of the deregulated pp60c-src. Expression of deregulated Xenopus fyn, a src-family member, resulted in a phenotype similar to that seen with deregulated src. However, in the fyn-injected oocytes, many more proteins were phosphorylated on tyrosine than in the src-injected oocytes. Progesterone stimulation of oocytes expressing deregulated pp60c-src resulted in an increase in the number of tyrosine-phosphorylated proteins. This change may represent the response of pp60src to the resumption of the cell cycle in maturing oocytes. These data suggest that the oocyte may be a particularly useful system for investigating the role of pp60c-src in the regulation of cytoskeletal structure and in the regulation of events associated with the cell cycle."} {"id": "PMID:1280324", "title": "Association of Src-like protein tyrosine kinases with the CD2 cell surface molecule in rat T lymphocytes and natural killer cells.", "content": "The cell surface molecule CD2 has a signaling role in the activation of T lymphocytes and natural killer cells. Because perturbation of CD2 leads to the appearance of tyrosine-phosphorylated proteins, we investigated the possibility that CD2 associates with cytoplasmic protein tyrosine kinases. As determined by in vitro kinase assays and phosphoamino acid analysis, protein tyrosine kinase activity coprecipitated with CD2 from rat T lymphocytes, T lymphoblasts, thymocytes, interleukin-2-activated natural killer cells, and RNK-16 cells (a rat natural killer cell line). In each case, both p56lck and p59fyn were identified in the CD2 immunoprecipitate. In the thymus, the association between CD2 and these kinases occurred predominately in a small subset of thymocytes that had the cell surface phenotype of mature T cells, indicating that the association is a regulated event and occurs late in T-cell ontogeny. The finding that CD2 is associated with p56lck and p59fyn in detergent lysates suggests that interactions with these Src-like protein kinases play a critical role in CD2-mediated signal transduction.", "contents": "Association of Src-like protein tyrosine kinases with the CD2 cell surface molecule in rat T lymphocytes and natural killer cells. The cell surface molecule CD2 has a signaling role in the activation of T lymphocytes and natural killer cells. Because perturbation of CD2 leads to the appearance of tyrosine-phosphorylated proteins, we investigated the possibility that CD2 associates with cytoplasmic protein tyrosine kinases. As determined by in vitro kinase assays and phosphoamino acid analysis, protein tyrosine kinase activity coprecipitated with CD2 from rat T lymphocytes, T lymphoblasts, thymocytes, interleukin-2-activated natural killer cells, and RNK-16 cells (a rat natural killer cell line). In each case, both p56lck and p59fyn were identified in the CD2 immunoprecipitate. In the thymus, the association between CD2 and these kinases occurred predominately in a small subset of thymocytes that had the cell surface phenotype of mature T cells, indicating that the association is a regulated event and occurs late in T-cell ontogeny. The finding that CD2 is associated with p56lck and p59fyn in detergent lysates suggests that interactions with these Src-like protein kinases play a critical role in CD2-mediated signal transduction."} {"id": "PMID:1280325", "title": "Novel member of the zinc finger superfamily: A C2-HC finger that recognizes a glia-specific gene.", "content": "A novel member of the zinc finger superfamily was cloned by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein (PLP) gene. Named MyTI (myelin transcription factor I), this gene is most highly transcribed in the developing nervous system, where expression precedes induction of its presumptive target, PLP. Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis. Zinc is a necessary cofactor for DNA binding of MyTI, as the zinc-chelating agent 1,10-orthophenanthroline eliminates binding activity. Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement. The MyTI protein has six fingers of the C2-HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites. The six fingers are highly conserved, suggesting that they arose from successive duplication events, while the linker regions diverge in size and sequence. Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters. MyTI may therefore be the prototype of a new structural family of zinc-stabilized DNA binding proteins.", "contents": "Novel member of the zinc finger superfamily: A C2-HC finger that recognizes a glia-specific gene. A novel member of the zinc finger superfamily was cloned by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein (PLP) gene. Named MyTI (myelin transcription factor I), this gene is most highly transcribed in the developing nervous system, where expression precedes induction of its presumptive target, PLP. Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis. Zinc is a necessary cofactor for DNA binding of MyTI, as the zinc-chelating agent 1,10-orthophenanthroline eliminates binding activity. Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement. The MyTI protein has six fingers of the C2-HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites. The six fingers are highly conserved, suggesting that they arose from successive duplication events, while the linker regions diverge in size and sequence. Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters. MyTI may therefore be the prototype of a new structural family of zinc-stabilized DNA binding proteins."} {"id": "PMID:1280326", "title": "The SH2- and SH3-containing Nck protein transforms mammalian fibroblasts in the absence of elevated phosphotyrosine levels.", "content": "We have established the human nck sequence as a new oncogene. Nck encodes one SH2 and three SH3 domains, the Src homology motifs found in nonreceptor tyrosine kinases, Ras GTPase-activating protein, phosphatidylinositol 3-kinase, and phospholipase C-gamma. Overexpression of human nck in 3Y1 rat fibroblasts results in transformation as judged by alteration of cell morphology, colony formation in soft agar, and tumor formation in nude BALB/c mice. However, overexpression of nck does not induce detectable elevation of the phosphotyrosine content of specific proteins, as is observed for v-crk, another SH2/SH3-containing oncogene. Despite this fact, we demonstrate that Nck retains the ability to bind tyrosine phosphorylated proteins in vitro, using a fusion protein of Nck with glutathione-S-transferase (GST). Moreover, when incubated with lysates prepared from v-src-transformed 3Y1 cells or the nck-overexpressing cell lines, GST-Nck binds to both p60v-src and serine/threonine kinases, respectively. Although phosphotyrosine levels are not elevated in the nck-expressing fibroblasts, vanadate treatment of these cells results in a phosphotyrosine pattern that is altered from the parental 3Y1 pattern, suggestive of a perturbation of indigenous tyrosine kinase pathways. These results suggest the possibility that human nck induces transformation in 3Y1 fibroblasts by virtue of its altered affinity or specificity for the normal substrates of its rat homolog and that Nck may play a role in linking tyrosine and serine/threonine kinase pathways within the cell.", "contents": "The SH2- and SH3-containing Nck protein transforms mammalian fibroblasts in the absence of elevated phosphotyrosine levels. We have established the human nck sequence as a new oncogene. Nck encodes one SH2 and three SH3 domains, the Src homology motifs found in nonreceptor tyrosine kinases, Ras GTPase-activating protein, phosphatidylinositol 3-kinase, and phospholipase C-gamma. Overexpression of human nck in 3Y1 rat fibroblasts results in transformation as judged by alteration of cell morphology, colony formation in soft agar, and tumor formation in nude BALB/c mice. However, overexpression of nck does not induce detectable elevation of the phosphotyrosine content of specific proteins, as is observed for v-crk, another SH2/SH3-containing oncogene. Despite this fact, we demonstrate that Nck retains the ability to bind tyrosine phosphorylated proteins in vitro, using a fusion protein of Nck with glutathione-S-transferase (GST). Moreover, when incubated with lysates prepared from v-src-transformed 3Y1 cells or the nck-overexpressing cell lines, GST-Nck binds to both p60v-src and serine/threonine kinases, respectively. Although phosphotyrosine levels are not elevated in the nck-expressing fibroblasts, vanadate treatment of these cells results in a phosphotyrosine pattern that is altered from the parental 3Y1 pattern, suggestive of a perturbation of indigenous tyrosine kinase pathways. These results suggest the possibility that human nck induces transformation in 3Y1 fibroblasts by virtue of its altered affinity or specificity for the normal substrates of its rat homolog and that Nck may play a role in linking tyrosine and serine/threonine kinase pathways within the cell."} {"id": "PMID:1280327", "title": "Regulation of parathyroid hormone-related peptide (PTHrP) gene transcription: cell- and tissue-specific promoter utilization mediated by multiple positive and negative cis-acting DNA elements.", "content": "The gene encoding PTH-related peptide (PTHrP) is expressed in a wide variety of normal and neoplastic tissues. Increased PTHrP gene expression in and secretion of PTHrP by specific tumors directly contributes to the development of malignancy-associated hypercalcemia in vivo. To define the genetic elements important for the control of PTHrP gene transcription, we used the reverse transcription polymerase chain reaction to delineate the control of promoter utilization and the splicing patterns of the exons encoding 5'-untranslated sequences. The majority of normal and neoplastic human tissues contained PTHrP mRNA transcripts initiating from both the up-stream (P1) and down-stream (P2) human PTHrP promoters. Furthermore, the downstream promoter was preferentially used by a factor of more than 30-fold. P1-initiated transcripts contained RNA species both with and without exon 2 (E2) sequences, except in the pancreas, adrenal, and stomach, where E2-containing sequences predominated. The transcriptional activities of P1, P2, and P1 + P2 were assessed by transfection of the corresponding PTHrP-chloramphenicol acetyltransferase (CAT) fusion genes into heterologous cell lines. Fusion genes containing P2 sequences were more transcriptionally active than fusion genes containing P1 sequences. The transcriptional activities of P1 + P2 in their natural tandem orientation were additive in rat keratinocytes and human JEG choriocarcinoma cells. In contrast, the activity of P1 + P2 was less than that of P2 alone in hamster BHK fibroblasts and InR1-G9 cells, and human HeLa cells. Analysis of the transcriptional properties of 5'-deleted human PTHrP-CAT constructs revealed the presence of multiple positive and negative DNA sequences (within both P1 and P2) functionally important for human PTHrP gene transcription. Distinct positive and negative DNA elements were also identified from analysis of 5'-deleted rat PTHrP-CAT fusion genes. The results of these experiments provide evidence for cell- and tissue-specific utilization of 1) distinct human PTHrP transcription start sites and specific patterns of 5'-exon splicing and 2) multiple positive and negative DNA control elements, important for the regulation of human and rat PTHrP gene transcription.", "contents": "Regulation of parathyroid hormone-related peptide (PTHrP) gene transcription: cell- and tissue-specific promoter utilization mediated by multiple positive and negative cis-acting DNA elements. The gene encoding PTH-related peptide (PTHrP) is expressed in a wide variety of normal and neoplastic tissues. Increased PTHrP gene expression in and secretion of PTHrP by specific tumors directly contributes to the development of malignancy-associated hypercalcemia in vivo. To define the genetic elements important for the control of PTHrP gene transcription, we used the reverse transcription polymerase chain reaction to delineate the control of promoter utilization and the splicing patterns of the exons encoding 5'-untranslated sequences. The majority of normal and neoplastic human tissues contained PTHrP mRNA transcripts initiating from both the up-stream (P1) and down-stream (P2) human PTHrP promoters. Furthermore, the downstream promoter was preferentially used by a factor of more than 30-fold. P1-initiated transcripts contained RNA species both with and without exon 2 (E2) sequences, except in the pancreas, adrenal, and stomach, where E2-containing sequences predominated. The transcriptional activities of P1, P2, and P1 + P2 were assessed by transfection of the corresponding PTHrP-chloramphenicol acetyltransferase (CAT) fusion genes into heterologous cell lines. Fusion genes containing P2 sequences were more transcriptionally active than fusion genes containing P1 sequences. The transcriptional activities of P1 + P2 in their natural tandem orientation were additive in rat keratinocytes and human JEG choriocarcinoma cells. In contrast, the activity of P1 + P2 was less than that of P2 alone in hamster BHK fibroblasts and InR1-G9 cells, and human HeLa cells. Analysis of the transcriptional properties of 5'-deleted human PTHrP-CAT constructs revealed the presence of multiple positive and negative DNA sequences (within both P1 and P2) functionally important for human PTHrP gene transcription. Distinct positive and negative DNA elements were also identified from analysis of 5'-deleted rat PTHrP-CAT fusion genes. The results of these experiments provide evidence for cell- and tissue-specific utilization of 1) distinct human PTHrP transcription start sites and specific patterns of 5'-exon splicing and 2) multiple positive and negative DNA control elements, important for the regulation of human and rat PTHrP gene transcription."} {"id": "PMID:1280328", "title": "The CRES gene: a unique testis-regulated gene related to the cystatin family is highly restricted in its expression to the proximal region of the mouse epididymis.", "content": "As a result of examining regional-specific gene expression in the mouse epididymis, a novel cystatin-related epididymal specific (CRES) gene was identified. Substantial homology between the CRES gene and members of the cystatin family of cysteine proteinase inhibitors was observed at the amino acid level. This homology included the presence of four highly conserved cysteine residues in exact alignment with the cystatins as well as other regions of sequence characteristic of the cystatins. However, unlike the cystatins, the CRES gene does not contain specific highly conserved sequence motifs thought to be necessary for cysteine proteinase inhibitory activity. Also, in contrast to the ubiquitous expression of the cystatin C gene, Northern blot analysis and in situ hybridization demonstrated that the CRES gene is very restricted in its expression. The 0.75-kilobase CRES transcript is dramatically restricted to the very proximal caput region of the epididymis with 15- to 20-fold less expression in the testis and no expression detected in any of the other 24 tissues examined. In addition, the CRES transcript disappears 2-3 weeks after castration, suggesting a dependence on androgens. However, its expression remained undetectable even after the administration of testosterone or dihydrotestosterone. Unilateral castration also resulted in the disappearance of the CRES mRNA from the castrate epididymis, but not from the intact epididymis, suggesting that testicular factors or hormones other than androgens may be involved in the regulation of CRES gene expression. Therefore, the unique sequence of the CRES gene as well as its highly restricted expression and unusual regulation by the testis suggests that it has a very specialized role in the epididymis.", "contents": "The CRES gene: a unique testis-regulated gene related to the cystatin family is highly restricted in its expression to the proximal region of the mouse epididymis. As a result of examining regional-specific gene expression in the mouse epididymis, a novel cystatin-related epididymal specific (CRES) gene was identified. Substantial homology between the CRES gene and members of the cystatin family of cysteine proteinase inhibitors was observed at the amino acid level. This homology included the presence of four highly conserved cysteine residues in exact alignment with the cystatins as well as other regions of sequence characteristic of the cystatins. However, unlike the cystatins, the CRES gene does not contain specific highly conserved sequence motifs thought to be necessary for cysteine proteinase inhibitory activity. Also, in contrast to the ubiquitous expression of the cystatin C gene, Northern blot analysis and in situ hybridization demonstrated that the CRES gene is very restricted in its expression. The 0.75-kilobase CRES transcript is dramatically restricted to the very proximal caput region of the epididymis with 15- to 20-fold less expression in the testis and no expression detected in any of the other 24 tissues examined. In addition, the CRES transcript disappears 2-3 weeks after castration, suggesting a dependence on androgens. However, its expression remained undetectable even after the administration of testosterone or dihydrotestosterone. Unilateral castration also resulted in the disappearance of the CRES mRNA from the castrate epididymis, but not from the intact epididymis, suggesting that testicular factors or hormones other than androgens may be involved in the regulation of CRES gene expression. Therefore, the unique sequence of the CRES gene as well as its highly restricted expression and unusual regulation by the testis suggests that it has a very specialized role in the epididymis."} {"id": "PMID:1280329", "title": "Gonadotrope- and thyrotrope-specific expression of the human and bovine glycoprotein hormone alpha-subunit genes is regulated by distinct cis-acting elements.", "content": "The proximal 5'-flanking region of the alpha-subunit gene from humans and cattle confers pituitary-specific expression to heterologous reporter genes in transgenic mice. To investigate whether these promoter regions also contain the necessary regulatory elements for cell-specific expression and hormonal regulation, we used three independent lines of transgenic mice. Two lines of transgenic mice contained chimeric genes consisting of either 1.6 kilobasepairs (kbp) of human or 3 15 basepairs of bovine alpha-subunit proximal 5'-flanking sequence linked to the bacterial gene encoding chloramphenicol acetyltransferase (CAT). A third line of transgenic mice contained the proximal 1.6 kbp of 5'-flanking sequence of the human alpha-subunit gene linked to the bacterial lacZ gene encoding beta-galactosidase (beta gal; H alpha beta gal transgenic mice). Hormonal replacement paradigms indicate that both human and bovine alpha CAT transgenes are regulated by GnRH, suggesting that their expression occurs in gonadotropes. Thus, the proximal 5'-flanking regions of both the human and bovine alpha-subunit genes must contain regulatory elements that confer both gonadotrope-specific expression and responsiveness to GnRH. In contrast to the human alpha-subunit promoter, the bovine alpha-subunit promoter lacks a functional cAMP response element, suggesting that transduction of both cell-specific and GnRH transcriptional signals occurs through cAMP response element-independent pathways. Thyrotropes also express the glycoprotein hormone alpha-subunit gene. Yet, hormone replacement paradigms with propylthiouracil and T3 were ineffective in altering CAT activity in the pituitary of human or bovine alpha CAT transgenic mice. Because a thyroid hormone response element has been localized to the proximal 5'-flanking region of the human alpha-subunit gene, these data suggest that the alpha CAT transgenes lack sufficient information to direct expression to thyrotropes. Direct evidence for this possibility was obtained through immunocytochemical studies performed on pituitaries from H alpha beta gal transgenic mice. beta-Galactosidase activity appeared in gonadotropes, but not thyrotropes. We conclude, therefore, that distinct and separable regulatory elements mediate the expression of the alpha-subunit gene in gonadotropes and thyrotropes.", "contents": "Gonadotrope- and thyrotrope-specific expression of the human and bovine glycoprotein hormone alpha-subunit genes is regulated by distinct cis-acting elements. The proximal 5'-flanking region of the alpha-subunit gene from humans and cattle confers pituitary-specific expression to heterologous reporter genes in transgenic mice. To investigate whether these promoter regions also contain the necessary regulatory elements for cell-specific expression and hormonal regulation, we used three independent lines of transgenic mice. Two lines of transgenic mice contained chimeric genes consisting of either 1.6 kilobasepairs (kbp) of human or 3 15 basepairs of bovine alpha-subunit proximal 5'-flanking sequence linked to the bacterial gene encoding chloramphenicol acetyltransferase (CAT). A third line of transgenic mice contained the proximal 1.6 kbp of 5'-flanking sequence of the human alpha-subunit gene linked to the bacterial lacZ gene encoding beta-galactosidase (beta gal; H alpha beta gal transgenic mice). Hormonal replacement paradigms indicate that both human and bovine alpha CAT transgenes are regulated by GnRH, suggesting that their expression occurs in gonadotropes. Thus, the proximal 5'-flanking regions of both the human and bovine alpha-subunit genes must contain regulatory elements that confer both gonadotrope-specific expression and responsiveness to GnRH. In contrast to the human alpha-subunit promoter, the bovine alpha-subunit promoter lacks a functional cAMP response element, suggesting that transduction of both cell-specific and GnRH transcriptional signals occurs through cAMP response element-independent pathways. Thyrotropes also express the glycoprotein hormone alpha-subunit gene. Yet, hormone replacement paradigms with propylthiouracil and T3 were ineffective in altering CAT activity in the pituitary of human or bovine alpha CAT transgenic mice. Because a thyroid hormone response element has been localized to the proximal 5'-flanking region of the human alpha-subunit gene, these data suggest that the alpha CAT transgenes lack sufficient information to direct expression to thyrotropes. Direct evidence for this possibility was obtained through immunocytochemical studies performed on pituitaries from H alpha beta gal transgenic mice. beta-Galactosidase activity appeared in gonadotropes, but not thyrotropes. We conclude, therefore, that distinct and separable regulatory elements mediate the expression of the alpha-subunit gene in gonadotropes and thyrotropes."} {"id": "PMID:1280330", "title": "Drosophila wingless generates cell type diversity among engrailed expressing cells.", "content": "During embryogenesis, body pattern is established in a stepwise process. After specification of the body axis, the embryo is subdivided into smaller units. Within these units, a diverse array of cell types is then generated. The subdivisions of the Drosophila embryo, called parasegments, are defined by the interface between cells expressing the homeoprotein Engrailed and cells expressing the secreted protein Wingless. We have examined the generation of cell-type diversity within parasegments by focusing on the choice of cell fate made by the engrailed (en)-expressing cells. These cells differentiate as one of two alternative cell types. We report here that this choice is mediated by wingless (wg), in a function distinct from its early role maintaining en expression. Thus, en cells exhibit different responses to the wg signal at different developmental stages. Early wg input stabilizes the subdivision of the body axis by maintaining en expression, whereas later input generates cell-type diversity.", "contents": "Drosophila wingless generates cell type diversity among engrailed expressing cells. During embryogenesis, body pattern is established in a stepwise process. After specification of the body axis, the embryo is subdivided into smaller units. Within these units, a diverse array of cell types is then generated. The subdivisions of the Drosophila embryo, called parasegments, are defined by the interface between cells expressing the homeoprotein Engrailed and cells expressing the secreted protein Wingless. We have examined the generation of cell-type diversity within parasegments by focusing on the choice of cell fate made by the engrailed (en)-expressing cells. These cells differentiate as one of two alternative cell types. We report here that this choice is mediated by wingless (wg), in a function distinct from its early role maintaining en expression. Thus, en cells exhibit different responses to the wg signal at different developmental stages. Early wg input stabilizes the subdivision of the body axis by maintaining en expression, whereas later input generates cell-type diversity."} {"id": "PMID:1280331", "title": "Ornithine decarboxylase activity is critical for cell transformation.", "content": "The enzyme ornithine decarboxylase is the key regulator of the synthesis of polyamines which are essential for cell proliferation. Expression of this enzyme is transiently increased upon stimulation by growth factors, but becomes constitutively activated during cell transformation induced by carcinogens, viruses or oncogenes. To test whether ornithine decarboxylase could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 cells with expression vectors carrying the complementary DNA encoding human ornithine decarboxylase in sense and antisense orientations. The increased expression of the enzyme (50-100-times endogenous levels) induced not only cell transformation, but also anchorage-independent growth in soft agar and increased tyrosine phosphorylation of a protein of M(r) 130K. Expression of ornithine decarboxylase antisense RNA was associated with an epithelioid morphology and reduced cell proliferation. Moreover, blocking the endogenous enzyme using specific inhibitor or synthesizing antisense RNA prevented transformation of rat fibroblasts by temperature-sensitive v-src oncogene. Our results imply that the gene encoding ornithine decarboxylase is a proto-oncogene central for regulation of cell growth and transformation.", "contents": "Ornithine decarboxylase activity is critical for cell transformation. The enzyme ornithine decarboxylase is the key regulator of the synthesis of polyamines which are essential for cell proliferation. Expression of this enzyme is transiently increased upon stimulation by growth factors, but becomes constitutively activated during cell transformation induced by carcinogens, viruses or oncogenes. To test whether ornithine decarboxylase could be a common mediator of transformation and oncogenic itself, we transfected NIH3T3 cells with expression vectors carrying the complementary DNA encoding human ornithine decarboxylase in sense and antisense orientations. The increased expression of the enzyme (50-100-times endogenous levels) induced not only cell transformation, but also anchorage-independent growth in soft agar and increased tyrosine phosphorylation of a protein of M(r) 130K. Expression of ornithine decarboxylase antisense RNA was associated with an epithelioid morphology and reduced cell proliferation. Moreover, blocking the endogenous enzyme using specific inhibitor or synthesizing antisense RNA prevented transformation of rat fibroblasts by temperature-sensitive v-src oncogene. Our results imply that the gene encoding ornithine decarboxylase is a proto-oncogene central for regulation of cell growth and transformation."} {"id": "PMID:1280332", "title": "Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease.", "content": "The central pathological feature of human kidney disease that leads to kidney failure is the accumulation of extracellular matrix in glomeruli. Overexpression of transforming growth factor-beta (TGF-beta) underlies the accumulation of pathological matrix in experimental glomerulonephritis. Administration of an antibody raised against TGF-beta to glomerulonephritic rats suppresses glomerular matrix production and prevents matrix accumulation in the injured glomeruli. One of the matrix components induced by TGF-beta, the proteoglycan decorin, can bind TGF-beta and neutralize its biological activity, so decorin may be a natural regulator of TGF-beta (refs 3, 4). We tested whether decorin could antagonize the action of TGF-beta in vivo using the experimental glomerulonephritis model. We report here that administration of decorin inhibits the increased production of extracellular matrix and attenuates manifestations of disease, confirming our hypothesis. On the basis of our results, decorin may eventually prove to be clinically useful in diseases associated with overproduction of TGF-beta.", "contents": "Natural inhibitor of transforming growth factor-beta protects against scarring in experimental kidney disease. The central pathological feature of human kidney disease that leads to kidney failure is the accumulation of extracellular matrix in glomeruli. Overexpression of transforming growth factor-beta (TGF-beta) underlies the accumulation of pathological matrix in experimental glomerulonephritis. Administration of an antibody raised against TGF-beta to glomerulonephritic rats suppresses glomerular matrix production and prevents matrix accumulation in the injured glomeruli. One of the matrix components induced by TGF-beta, the proteoglycan decorin, can bind TGF-beta and neutralize its biological activity, so decorin may be a natural regulator of TGF-beta (refs 3, 4). We tested whether decorin could antagonize the action of TGF-beta in vivo using the experimental glomerulonephritis model. We report here that administration of decorin inhibits the increased production of extracellular matrix and attenuates manifestations of disease, confirming our hypothesis. On the basis of our results, decorin may eventually prove to be clinically useful in diseases associated with overproduction of TGF-beta."} {"id": "PMID:1280333", "title": "Molecular analysis of the association of HLA-B53 and resistance to severe malaria.", "content": "The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component.", "contents": "Molecular analysis of the association of HLA-B53 and resistance to severe malaria. The protective association between the human leukocyte antigen HLA-B53 and severe malaria was investigated by sequencing of peptides eluted from this molecule followed by screening of candidate epitopes from pre-erythrocytic-stage antigens of Plasmodium falciparum in biochemical and cellular assays. Among malaria-immune Africans, HLA-B53-restricted cytotoxic T lymphocytes recognized a conserved nonamer peptide from liver-stage-specific antigen-1 (LSA-1), but no HLA-B53-restricted epitopes were identified in other antigens. These findings indicate a possible molecular basis for this HLA-disease association and support the candidacy of liver-stage-specific antigen-1 as a malaria vaccine component."} {"id": "PMID:1280334", "title": "Primary structure and functional characterization of a high-affinity glutamate transporter.", "content": "Glutamate transport across plasma membranes of neurons, glial cells and epithelial cells of the small intestine and kidney proceeds by high- and low-affinity transport systems. High-affinity (Km 2-50 microM) transport systems have been described that are dependent on Na+ but not Cl- ions and have a preference for L-glutamate and D- and L-aspartate. In neurons high-affinity glutamate transporters are essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. We have isolated a complementary DNA encoding an electrogenic Na(+)- but not Cl(-)-dependent high-affinity glutamate transporter (named EAAC1) from rabbit small intestine by expression in Xenopus oocytes. We find EAAC1 transcripts in specific neuronal structures in the central nervous system as well as in the small intestine, kidney, liver and heart. The function and pharmacology of the expressed protein are characteristic of the high-affinity glutamate transporter already identified in neuronal tissues. The abnormal glutamate transport that is associated with certain neurodegenerative diseases and which occurs during ischaemia and anoxia could be due to abnormalities in the function of this protein.", "contents": "Primary structure and functional characterization of a high-affinity glutamate transporter. Glutamate transport across plasma membranes of neurons, glial cells and epithelial cells of the small intestine and kidney proceeds by high- and low-affinity transport systems. High-affinity (Km 2-50 microM) transport systems have been described that are dependent on Na+ but not Cl- ions and have a preference for L-glutamate and D- and L-aspartate. In neurons high-affinity glutamate transporters are essential for terminating the postsynaptic action of glutamate by rapidly removing released glutamate from the synaptic cleft. We have isolated a complementary DNA encoding an electrogenic Na(+)- but not Cl(-)-dependent high-affinity glutamate transporter (named EAAC1) from rabbit small intestine by expression in Xenopus oocytes. We find EAAC1 transcripts in specific neuronal structures in the central nervous system as well as in the small intestine, kidney, liver and heart. The function and pharmacology of the expressed protein are characteristic of the high-affinity glutamate transporter already identified in neuronal tissues. The abnormal glutamate transport that is associated with certain neurodegenerative diseases and which occurs during ischaemia and anoxia could be due to abnormalities in the function of this protein."} {"id": "PMID:1280335", "title": "Control of RNase E-mediated RNA degradation by 5'-terminal base pairing in E. coli.", "content": "Despite the variety of messenger RNA half-lives in bacteria (0.5-30 min in Escherichia coli) and their importance in controlling gene expression, their molecular basis remains obscure. The lifetime of an entire mRNA molecule can be determined by features near its 5' end, but no 5' exoribonuclease has been identified in any prokaryotic organism. A mutation that inactivates E. coli RNase E also increases the average lifetime of bulk E. coli mRNA and of many individual messages, suggesting that cleavage by this endonuclease may be the rate-determining step in the degradation of most mRNAs in E. coli. We have investigated the substrate preference of RNase E in E. coli by using variants of RNA I, a small untranslated RNA whose swift degradation in vivo is initiated by RNase E cleavage at an internal site. We report here that RNase E has an unprecedented substrate specificity for an endoribonuclease, as it preferentially cleaves RNAs that have several unpaired nucleotides at the 5' end. The sensitivity of RNase E to 5'-terminal base pairing may explain how determinants near the 5' end can control rates of mRNA decay in bacteria.", "contents": "Control of RNase E-mediated RNA degradation by 5'-terminal base pairing in E. coli. Despite the variety of messenger RNA half-lives in bacteria (0.5-30 min in Escherichia coli) and their importance in controlling gene expression, their molecular basis remains obscure. The lifetime of an entire mRNA molecule can be determined by features near its 5' end, but no 5' exoribonuclease has been identified in any prokaryotic organism. A mutation that inactivates E. coli RNase E also increases the average lifetime of bulk E. coli mRNA and of many individual messages, suggesting that cleavage by this endonuclease may be the rate-determining step in the degradation of most mRNAs in E. coli. We have investigated the substrate preference of RNase E in E. coli by using variants of RNA I, a small untranslated RNA whose swift degradation in vivo is initiated by RNase E cleavage at an internal site. We report here that RNase E has an unprecedented substrate specificity for an endoribonuclease, as it preferentially cleaves RNAs that have several unpaired nucleotides at the 5' end. The sensitivity of RNase E to 5'-terminal base pairing may explain how determinants near the 5' end can control rates of mRNA decay in bacteria."} {"id": "PMID:1280336", "title": "N-methyl-D-aspartate receptor antagonists counteract the long lasting 5-HT1A receptor-induced attenuation of postsynaptic responses in the rat in vivo.", "content": "The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists dizocilpine and phenycyclidine, the competitive NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the antagonist at the glycine modulatory site of the NMDA receptor, 3-amino-1-hydroxy-2-pyrrolidone (HA-966) on the long lasting attenuation of some post-synaptic 5-HT1A receptor-mediated responses in rats (increased corticosterone secretion and inhibition of the cage leaving response) produced by a single injection of the 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied. It was found that these antagonists counteracted the attenuation of these responses at dose levels known to block the NMDA receptor-ion channel complex in vivo. It is concluded that the long lasting attenuation of postsynaptic responses after a 5-HT1A receptor agonist is initiated through stimulation of glutamate NMDA receptors indicating a functional interaction between the 5-HT and glutamate systems in at least two different models.", "contents": "N-methyl-D-aspartate receptor antagonists counteract the long lasting 5-HT1A receptor-induced attenuation of postsynaptic responses in the rat in vivo. The effect of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists dizocilpine and phenycyclidine, the competitive NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) and the antagonist at the glycine modulatory site of the NMDA receptor, 3-amino-1-hydroxy-2-pyrrolidone (HA-966) on the long lasting attenuation of some post-synaptic 5-HT1A receptor-mediated responses in rats (increased corticosterone secretion and inhibition of the cage leaving response) produced by a single injection of the 5-hydroxytryptamine1A (5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) was studied. It was found that these antagonists counteracted the attenuation of these responses at dose levels known to block the NMDA receptor-ion channel complex in vivo. It is concluded that the long lasting attenuation of postsynaptic responses after a 5-HT1A receptor agonist is initiated through stimulation of glutamate NMDA receptors indicating a functional interaction between the 5-HT and glutamate systems in at least two different models."} {"id": "PMID:1280337", "title": "Positron emission tomographic measurement of acute hemodynamic changes in primate middle cerebral artery occlusion.", "content": "Specific hemodynamic changes in acute ischemia were investigated using a middle cerebral artery occlusion primate model and positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate for oxygen were measured 1, 3, and 9 hours after occlusion. OEF showed an increase in ischemic areas, and especially where CBF was below 18 ml/100 gm/min 1 hour after occlusion the OEF increased significantly (0.69 +/- 0.20, p < 0.05). Nine hours after occlusion, the OEF values were lower compared to those 1 and 3 hours after occlusion. Areas where CBF ranged from 18 to 31 ml/100 gm/min showed an increase in OEF at all times (p < 0.05). Clearly, OEF changes remarkably in the acute stage.", "contents": "Positron emission tomographic measurement of acute hemodynamic changes in primate middle cerebral artery occlusion. Specific hemodynamic changes in acute ischemia were investigated using a middle cerebral artery occlusion primate model and positron emission tomography. The cerebral blood flow (CBF), cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate for oxygen were measured 1, 3, and 9 hours after occlusion. OEF showed an increase in ischemic areas, and especially where CBF was below 18 ml/100 gm/min 1 hour after occlusion the OEF increased significantly (0.69 +/- 0.20, p < 0.05). Nine hours after occlusion, the OEF values were lower compared to those 1 and 3 hours after occlusion. Areas where CBF ranged from 18 to 31 ml/100 gm/min showed an increase in OEF at all times (p < 0.05). Clearly, OEF changes remarkably in the acute stage."} {"id": "PMID:1280338", "title": "Isolation, purification, and characterization of an acidic protein in the cerebrospinal fluid of central nervous system disease.", "content": "Proteins from 21 cerebrospinal fluid (CSF) samples (14 derived from neurological cases and 7 from normal individuals) and 15 serum samples (11 from neurological cases and 4 from normal individuals) were analyzed by two-dimensional electrophoresis. Protein mapping revealed a very acidic protein (Ac-P) at about pH 3.5 in the 71% of CSF samples from neurological cases. However, no serum sample contained Ac-P. Ac-P was isolated and purified, and determined to be a glycoprotein containing a large amount of carbohydrate, with molecular weight 42,000 and isoelectric point 2.7-3.3. The amino acid composition of Ac-P was consistent with alpha 1-acid glycoprotein (AGP), and Ac-P was responsive to a commercial anti-AGP antiserum in the radial immunodiffusion test. The known polymorphism of AGP suggests some differences in physicochemical properties such as molecular weight and isoelectric point between AGP in serum and in CSF. Quantitative analysis of Ac-P (AGP) and total protein levels in CSF showed a partial interdependence. Ac-P may be a useful marker for detecting a pathological conditions of the central nervous system.", "contents": "Isolation, purification, and characterization of an acidic protein in the cerebrospinal fluid of central nervous system disease. Proteins from 21 cerebrospinal fluid (CSF) samples (14 derived from neurological cases and 7 from normal individuals) and 15 serum samples (11 from neurological cases and 4 from normal individuals) were analyzed by two-dimensional electrophoresis. Protein mapping revealed a very acidic protein (Ac-P) at about pH 3.5 in the 71% of CSF samples from neurological cases. However, no serum sample contained Ac-P. Ac-P was isolated and purified, and determined to be a glycoprotein containing a large amount of carbohydrate, with molecular weight 42,000 and isoelectric point 2.7-3.3. The amino acid composition of Ac-P was consistent with alpha 1-acid glycoprotein (AGP), and Ac-P was responsive to a commercial anti-AGP antiserum in the radial immunodiffusion test. The known polymorphism of AGP suggests some differences in physicochemical properties such as molecular weight and isoelectric point between AGP in serum and in CSF. Quantitative analysis of Ac-P (AGP) and total protein levels in CSF showed a partial interdependence. Ac-P may be a useful marker for detecting a pathological conditions of the central nervous system."} {"id": "PMID:1280339", "title": "Prognosis of primary malignant lymphoma of the central nervous system--a retrospective study of 32 cases.", "content": "A retrospective analysis of 32 patients with primary malignant lymphoma of the central nervous system (CNS) diagnosed between 1976 and 1989 investigated treatment results and recurrence patterns. All patients showed either complete or partial regression of the tumor after initial treatment, mainly radiation therapy with adjuvant chemotherapy. The mean dose of whole-brain irradiation was 40.9 Gy and that of booster was 14.4 Gy. Most patients had tumor recurrence. The median time to recurrence from completion of the treatment was 5 months. The 1- and 5-year survival rates were 50.0 and 17.7%, respectively, and the overall median survival time was 11 months. Most tumors had multiple recurrences at the primary site and other regions of the CNS, and tended to recur in the periventricular region and the cerebrospinal fluid space. Spinal metastasis occurred in five cases. The importance of good control of the primary lesion and active maintenance therapy for the whole CNS is emphasized.", "contents": "Prognosis of primary malignant lymphoma of the central nervous system--a retrospective study of 32 cases. A retrospective analysis of 32 patients with primary malignant lymphoma of the central nervous system (CNS) diagnosed between 1976 and 1989 investigated treatment results and recurrence patterns. All patients showed either complete or partial regression of the tumor after initial treatment, mainly radiation therapy with adjuvant chemotherapy. The mean dose of whole-brain irradiation was 40.9 Gy and that of booster was 14.4 Gy. Most patients had tumor recurrence. The median time to recurrence from completion of the treatment was 5 months. The 1- and 5-year survival rates were 50.0 and 17.7%, respectively, and the overall median survival time was 11 months. Most tumors had multiple recurrences at the primary site and other regions of the CNS, and tended to recur in the periventricular region and the cerebrospinal fluid space. Spinal metastasis occurred in five cases. The importance of good control of the primary lesion and active maintenance therapy for the whole CNS is emphasized."} {"id": "PMID:1280340", "title": "Analysis of retained ventricular shunt catheters.", "content": "To identify the causes of ventricular shunt catheter retention, 42 shunt removals in 28 patients in our neurosurgical clinic from 1982 to 1991 were analyzed. The mean patient age was 13.8 years (2 mos-78 yrs), and mean shunt duration was 20.1 months (0.5-94 mos). There were nine retained ventricular catheters, including five with obstruction of the ventricular catheter. Shunt duration was significantly longer compared with the unretained group. Three retained ventricular catheters were stained by HE for histological examination. Light microscopy showed the inner lumen of catheters filled with granulomatous connective tissue and reactive glial tissue, and giant cell reaction to silicone material. Scanning electron microscopy of two catheters found peeling on the inner surface of the catheter, evidence of aging of the material. Granulomatous connective tissue and glial tissue reaction to aged silicone are suggested as the cause of catheter retention.", "contents": "Analysis of retained ventricular shunt catheters. To identify the causes of ventricular shunt catheter retention, 42 shunt removals in 28 patients in our neurosurgical clinic from 1982 to 1991 were analyzed. The mean patient age was 13.8 years (2 mos-78 yrs), and mean shunt duration was 20.1 months (0.5-94 mos). There were nine retained ventricular catheters, including five with obstruction of the ventricular catheter. Shunt duration was significantly longer compared with the unretained group. Three retained ventricular catheters were stained by HE for histological examination. Light microscopy showed the inner lumen of catheters filled with granulomatous connective tissue and reactive glial tissue, and giant cell reaction to silicone material. Scanning electron microscopy of two catheters found peeling on the inner surface of the catheter, evidence of aging of the material. Granulomatous connective tissue and glial tissue reaction to aged silicone are suggested as the cause of catheter retention."} {"id": "PMID:1280341", "title": "Abscess within a glioblastoma multiforme--case report.", "content": "A rare case of abscess within a glioblastoma with an unusual presentation occurred in a 46-year-old female who developed right hemiparesis and seizure. Computed tomography and magnetic resonance imaging demonstrated hemorrhage which mimicked hemorrhagic infarction. However, the lesions developed ring enhancement. Aspiration showed one to be an abscess, which collapsed by drainage but later re-expanded. The mass was removed, and histological examination revealed glioblastoma.", "contents": "Abscess within a glioblastoma multiforme--case report. A rare case of abscess within a glioblastoma with an unusual presentation occurred in a 46-year-old female who developed right hemiparesis and seizure. Computed tomography and magnetic resonance imaging demonstrated hemorrhage which mimicked hemorrhagic infarction. However, the lesions developed ring enhancement. Aspiration showed one to be an abscess, which collapsed by drainage but later re-expanded. The mass was removed, and histological examination revealed glioblastoma."} {"id": "PMID:1280342", "title": "Granulomatous angiitis of the central nervous system--a case with recurrent intracerebral hemorrhage.", "content": "Granulomatous angiitis of the central nervous system occurred in a 43-year-old male presenting with recurrent intracerebral hemorrhage confirmed by computed tomography. A surgical specimen obtained at hematoma removal revealed granulomatous angiitis. Systemic investigation found no underlying cause for the hemorrhage. Although the incidence is very low, this condition should be considered in cases of recurrent intracerebral hemorrhage with unknown cause. When surgery is indicated, biopsy of the brain and leptomeninges should be obtained, because involvement of the leptomeninges has occurred in virtually all autopsy cases.", "contents": "Granulomatous angiitis of the central nervous system--a case with recurrent intracerebral hemorrhage. Granulomatous angiitis of the central nervous system occurred in a 43-year-old male presenting with recurrent intracerebral hemorrhage confirmed by computed tomography. A surgical specimen obtained at hematoma removal revealed granulomatous angiitis. Systemic investigation found no underlying cause for the hemorrhage. Although the incidence is very low, this condition should be considered in cases of recurrent intracerebral hemorrhage with unknown cause. When surgery is indicated, biopsy of the brain and leptomeninges should be obtained, because involvement of the leptomeninges has occurred in virtually all autopsy cases."} {"id": "PMID:1280343", "title": "Giant meningioma fed by the anterior choroidal artery: successful removal following embolization--case report.", "content": "A 53-year-old female was admitted with apathy, left sensory and motor disturbance, left homonymous hemianopsia, and dressing apraxia. Computed tomography and magnetic resonance imaging showed a huge mass markedly enhanced in and around the right trigone. Cerebral angiography revealed rich vascularity of the tumor mainly fed by the right anterior choroidal artery. The feeding vessel was embolized with microfibrillar collagen after superselective catheterization. Seven days later, the tumor was totally removed with low blood loss. The histological diagnosis was fibroblastic meningioma. She was discharged without neurological deficit, except for left homonymous hemianopsia.", "contents": "Giant meningioma fed by the anterior choroidal artery: successful removal following embolization--case report. A 53-year-old female was admitted with apathy, left sensory and motor disturbance, left homonymous hemianopsia, and dressing apraxia. Computed tomography and magnetic resonance imaging showed a huge mass markedly enhanced in and around the right trigone. Cerebral angiography revealed rich vascularity of the tumor mainly fed by the right anterior choroidal artery. The feeding vessel was embolized with microfibrillar collagen after superselective catheterization. Seven days later, the tumor was totally removed with low blood loss. The histological diagnosis was fibroblastic meningioma. She was discharged without neurological deficit, except for left homonymous hemianopsia."} {"id": "PMID:1280344", "title": "Thrombosed aneurysm of the middle cerebral artery with occlusion of the distal parent artery--case report.", "content": "A 54-year-old female presented with subarachnoid hemorrhage due to rupture of a small middle cerebral artery aneurysm, found to be thrombosed at surgery and not visualized on the preoperative angiograms. One major branch of the middle cerebral artery was found to be occluded near the trifurcation. The lumen of the branch proximal to the occlusion had appeared as the aneurysmal opacification on the preoperative angiograms.", "contents": "Thrombosed aneurysm of the middle cerebral artery with occlusion of the distal parent artery--case report. A 54-year-old female presented with subarachnoid hemorrhage due to rupture of a small middle cerebral artery aneurysm, found to be thrombosed at surgery and not visualized on the preoperative angiograms. One major branch of the middle cerebral artery was found to be occluded near the trifurcation. The lumen of the branch proximal to the occlusion had appeared as the aneurysmal opacification on the preoperative angiograms."} {"id": "PMID:1280345", "title": "Ruptured aneurysm arising from the anomalous anterior cerebral artery--case report.", "content": "A 64-year-old male presenting with subarachnoid hemorrhage had a saccular aneurysm arising from the anomalous anterior cerebral artery. The aneurysm was located on the curved mid-portion of the anomalous artery and extended underneath the right optic nerve. The aneurysm was clipped without unroofing the right optic canal. Postoperatively, he suffered from temporary mild deterioration of the right visual acuity. Hemodynamic stress may be important in the development of such aneurysms.", "contents": "Ruptured aneurysm arising from the anomalous anterior cerebral artery--case report. A 64-year-old male presenting with subarachnoid hemorrhage had a saccular aneurysm arising from the anomalous anterior cerebral artery. The aneurysm was located on the curved mid-portion of the anomalous artery and extended underneath the right optic nerve. The aneurysm was clipped without unroofing the right optic canal. Postoperatively, he suffered from temporary mild deterioration of the right visual acuity. Hemodynamic stress may be important in the development of such aneurysms."} {"id": "PMID:1280346", "title": "Pituitary metastasis of thyroid follicular adenocarcinoma--case report.", "content": "A rare case of pituitary metastasis of thyroid follicular adenocarcinoma occurred in a 62-year-old female manifesting as left retro-orbital pain and diplopia. Computed tomography and magnetic resonance imaging revealed a tumor in the pituitary fossa extending to the left cavernous sinus, sphenoid sinus, and prepontine cistern, destroying the upper portion of the clivus. An asymptomatic thyroid mass, probably malignant, was also found. She also had an incidental small meningioma in the posterior fossa. The pituitary tumor was partially removed, and the thyroid and posterior fossa tumors were totally removed in two operations. Both pituitary and thyroid tumors were verified to be follicular adenocarcinoma. Postoperatively, she developed panhypopituitarism for which cortisol and thyroxine replacement therapy was necessary. Three years after first therapy, she was alive but her symptoms did not improve.", "contents": "Pituitary metastasis of thyroid follicular adenocarcinoma--case report. A rare case of pituitary metastasis of thyroid follicular adenocarcinoma occurred in a 62-year-old female manifesting as left retro-orbital pain and diplopia. Computed tomography and magnetic resonance imaging revealed a tumor in the pituitary fossa extending to the left cavernous sinus, sphenoid sinus, and prepontine cistern, destroying the upper portion of the clivus. An asymptomatic thyroid mass, probably malignant, was also found. She also had an incidental small meningioma in the posterior fossa. The pituitary tumor was partially removed, and the thyroid and posterior fossa tumors were totally removed in two operations. Both pituitary and thyroid tumors were verified to be follicular adenocarcinoma. Postoperatively, she developed panhypopituitarism for which cortisol and thyroxine replacement therapy was necessary. Three years after first therapy, she was alive but her symptoms did not improve."} {"id": "PMID:1280347", "title": "[Angiogenesis induced by rat glioma cells in vitro].", "content": "Angiogenesis induced by rat glioma cells was examined in vitro using a double chamber co-culture system. Cultured microvascular endothelial cells from Fisher 344 rat brain, rat C6 glioma cells and rat T9 gliosarcoma cells were used for this study. Endothelial cells, cultured on type I collagen, formed capillary-like structures. In the co-culture system, C6 glioma cells promoted this formation. On the other hand T9 gliosarcoma cells had no effect on it. The supernatants of C6 glioma cells and T9 gliosarcoma cells suppressed the proliferation of the endothelial cells. C6 glioma cells probably produce and release soluble factors promoting angiogenesis. The proliferation of endothelial cells is thus suppressed while angiogenesis is made more intense. This in-vitro model is useful to elucidate the mechanism of tumor angiogenesis and to evaluate the promoting and inhibiting factors of angiogenesis.", "contents": "[Angiogenesis induced by rat glioma cells in vitro]. Angiogenesis induced by rat glioma cells was examined in vitro using a double chamber co-culture system. Cultured microvascular endothelial cells from Fisher 344 rat brain, rat C6 glioma cells and rat T9 gliosarcoma cells were used for this study. Endothelial cells, cultured on type I collagen, formed capillary-like structures. In the co-culture system, C6 glioma cells promoted this formation. On the other hand T9 gliosarcoma cells had no effect on it. The supernatants of C6 glioma cells and T9 gliosarcoma cells suppressed the proliferation of the endothelial cells. C6 glioma cells probably produce and release soluble factors promoting angiogenesis. The proliferation of endothelial cells is thus suppressed while angiogenesis is made more intense. This in-vitro model is useful to elucidate the mechanism of tumor angiogenesis and to evaluate the promoting and inhibiting factors of angiogenesis."} {"id": "PMID:1280348", "title": "Modulation of GABA release by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and N-methyl-D-aspartate receptors in matrix-enriched areas of the rat striatum.", "content": "Using a new in vitro superfusion device, the release of preloaded [3H]GABA was examined in microdiscs of tissues taken from sagittal slices in matrix-enriched areas of the rat striatum. Potassium (9 mM, 15 mM) stimulated the release of [3H]GABA in a concentration- and calcium-dependent manner and the veratridine (1 microM)-evoked release of [3H]GABA was completely abolished in the presence of tetrodotoxin (1 microM). The selective glutamatergic agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (1 mM) enhanced the potassium-evoked release of [3H]GABA as well as the basal outflow of [3H]GABA. This latter effect was found to be calcium-dependent, partially diminished by tetrodotoxin (1 microM), completely blocked by 6,7-dinitro-quinoxaline-2,3-dione (0.1 mM), which is generally used as an antagonist of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors, but not affected by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK801, 10 microM), a specific antagonist of N-methyl-D-aspartate receptors. Similarly, N-methyl-D-aspartate (1 mM) enhanced both the potassium (9 mM) and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (1 mM)-evoked release of [3H]GABA but when used alone, due to the presence of magnesium in the superfusion medium, was ineffective on the basal efflux of [3H]GABA. A stimulatory effect of N-methyl-D-aspartate (1 mM) on the basal outflow of [3H]GABA was observed, however, when magnesium was omitted from the superfusion medium. The stimulatory effect of N-methyl-D-aspartate (1 mM) observed in the presence of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate was not potentiated by glycine (1 microM, in the presence of strychnine 1 microM) and the N-methyl-D-aspartate-evoked response seen in the absence of magnesium was not enhanced by D-serine (1 mM), suggesting that endogenous glycine is already acting on N-methyl-D-aspartate receptors. In fact, in the absence of magnesium, 7-chloro-kynurenate (1 mM) completely abolished the stimulatory effect of N-methyl-D-aspartate on the release of [3H]GABA confirming that under our conditions, the glycine site of the N-methyl-D-aspartate receptor is saturated. N-methyl-D-aspartate-evoked responses were all blocked by MK801 (10 microM). Finally, the N-methyl-D-aspartate-evoked response seen in the absence of magnesium was markedly reduced in the presence of tetrodotoxin (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Modulation of GABA release by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate and N-methyl-D-aspartate receptors in matrix-enriched areas of the rat striatum. Using a new in vitro superfusion device, the release of preloaded [3H]GABA was examined in microdiscs of tissues taken from sagittal slices in matrix-enriched areas of the rat striatum. Potassium (9 mM, 15 mM) stimulated the release of [3H]GABA in a concentration- and calcium-dependent manner and the veratridine (1 microM)-evoked release of [3H]GABA was completely abolished in the presence of tetrodotoxin (1 microM). The selective glutamatergic agonist alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (1 mM) enhanced the potassium-evoked release of [3H]GABA as well as the basal outflow of [3H]GABA. This latter effect was found to be calcium-dependent, partially diminished by tetrodotoxin (1 microM), completely blocked by 6,7-dinitro-quinoxaline-2,3-dione (0.1 mM), which is generally used as an antagonist of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors, but not affected by (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK801, 10 microM), a specific antagonist of N-methyl-D-aspartate receptors. Similarly, N-methyl-D-aspartate (1 mM) enhanced both the potassium (9 mM) and the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (1 mM)-evoked release of [3H]GABA but when used alone, due to the presence of magnesium in the superfusion medium, was ineffective on the basal efflux of [3H]GABA. A stimulatory effect of N-methyl-D-aspartate (1 mM) on the basal outflow of [3H]GABA was observed, however, when magnesium was omitted from the superfusion medium. The stimulatory effect of N-methyl-D-aspartate (1 mM) observed in the presence of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate was not potentiated by glycine (1 microM, in the presence of strychnine 1 microM) and the N-methyl-D-aspartate-evoked response seen in the absence of magnesium was not enhanced by D-serine (1 mM), suggesting that endogenous glycine is already acting on N-methyl-D-aspartate receptors. In fact, in the absence of magnesium, 7-chloro-kynurenate (1 mM) completely abolished the stimulatory effect of N-methyl-D-aspartate on the release of [3H]GABA confirming that under our conditions, the glycine site of the N-methyl-D-aspartate receptor is saturated. N-methyl-D-aspartate-evoked responses were all blocked by MK801 (10 microM). Finally, the N-methyl-D-aspartate-evoked response seen in the absence of magnesium was markedly reduced in the presence of tetrodotoxin (1 microM).(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1280349", "title": "Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the putative excitatory neurotransmitter substance P.", "content": "The metabolic activity of several anatomically distinct brain areas was investigated by means of the quantitative autoradiographic 2-deoxy-D[1-14C]glucose method in awake rats following unilateral intranigral application of the putative excitatory neurotransmitter substance P. The primary goal was to determine the metabolic effects of substance P on the substantia nigra and its targets. Intranigral injection of 1 mM substance P (1.5 microliters) induced metabolic activation locally in the substantia nigra reticulata by 117% and substantia nigra compacta by 35%, as well as distally in the contralateral substantia nigra reticulata by 22% and contralateral substantia nigra compacta by 21%. All the basal ganglia components, the striatum, pallidum, entopeduncular, subthalamic nucleus and nucleus accumbens displayed bilateral metabolic activations after unilateral intranigral substance P injection. Among the principal reticulata efferent projections, the ventromedial, ventrolateral, parafascicular, mediodorsal and centrolateral thalamic nuclei, as well as the pedunculopontine nucleus displayed bilateral metabolic activations after intranigral substance P application. Moreover, unilateral intranigral substance P injection elicited metabolic activations in the thalamic and cortical components of the reticular, intralaminar, limbic and prefrontal systems, mostly bilateral. It is suggested that substance P applied into one substantia nigra reticulata activates the compacta nigrostriatal dopaminergic and the reticulata nigrothalamic GABAergic outputs inducing distal metabolic effects, similar to those elicited by unilateral nigral electrical stimulation [Savaki et al. (1983) J. comp. Neurol. 213, 46-65] and, opposite to several of those induced by intranigral injection of the inhibitory GABAA agonist muscimol [Savaki et al. (1992) Neuroscience 50, 781-794]. Furthermore, it is suggested that the ipsilateral basal ganglia effects induced by intranigral substance P application are mediated via both the compacta dopaminergic nigrostriatal projection and the reticulata GABAergic nigro-thalamocortico-striatal loop, whereas the contralateral basal ganglia and associated thalamocortical effects are due to the activation of the GABAergic reticulata efferents and are mediated via an interthalamic circuitry involving the motor, reticular and intralaminar thalamic nuclei.", "contents": "Bilateral cerebral metabolic effects of pharmacological manipulation of the substantia nigra in the rat: unilateral intranigral application of the putative excitatory neurotransmitter substance P. The metabolic activity of several anatomically distinct brain areas was investigated by means of the quantitative autoradiographic 2-deoxy-D[1-14C]glucose method in awake rats following unilateral intranigral application of the putative excitatory neurotransmitter substance P. The primary goal was to determine the metabolic effects of substance P on the substantia nigra and its targets. Intranigral injection of 1 mM substance P (1.5 microliters) induced metabolic activation locally in the substantia nigra reticulata by 117% and substantia nigra compacta by 35%, as well as distally in the contralateral substantia nigra reticulata by 22% and contralateral substantia nigra compacta by 21%. All the basal ganglia components, the striatum, pallidum, entopeduncular, subthalamic nucleus and nucleus accumbens displayed bilateral metabolic activations after unilateral intranigral substance P injection. Among the principal reticulata efferent projections, the ventromedial, ventrolateral, parafascicular, mediodorsal and centrolateral thalamic nuclei, as well as the pedunculopontine nucleus displayed bilateral metabolic activations after intranigral substance P application. Moreover, unilateral intranigral substance P injection elicited metabolic activations in the thalamic and cortical components of the reticular, intralaminar, limbic and prefrontal systems, mostly bilateral. It is suggested that substance P applied into one substantia nigra reticulata activates the compacta nigrostriatal dopaminergic and the reticulata nigrothalamic GABAergic outputs inducing distal metabolic effects, similar to those elicited by unilateral nigral electrical stimulation [Savaki et al. (1983) J. comp. Neurol. 213, 46-65] and, opposite to several of those induced by intranigral injection of the inhibitory GABAA agonist muscimol [Savaki et al. (1992) Neuroscience 50, 781-794]. Furthermore, it is suggested that the ipsilateral basal ganglia effects induced by intranigral substance P application are mediated via both the compacta dopaminergic nigrostriatal projection and the reticulata GABAergic nigro-thalamocortico-striatal loop, whereas the contralateral basal ganglia and associated thalamocortical effects are due to the activation of the GABAergic reticulata efferents and are mediated via an interthalamic circuitry involving the motor, reticular and intralaminar thalamic nuclei."} {"id": "PMID:1280350", "title": "Organization of the serotonergic innervation of spinal neurons in rats--I. Neuropeptide coexistence in varicosities innervating some spinothalamic tract neurons but not in those innervating postsynaptic dorsal column neurons.", "content": "Previous studies have suggested that peptides such as substance P and thyrotropin-releasing hormone coexist with serotonin in the same varicosities in the ventral horn and intermediate gray of the spinal cord in rat. However, coexistence of these peptides with serotonin is rare in fibers in the superficial dorsal horn. Since it has been proposed that serotonergic fibers in the superficial dorsal horn act to modulate nociception, it was hypothesized that the serotonergic neurons that contain neither substance P nor thyrotropin-releasing hormone might constitute a specifically antinociceptive subset of serotonergic neurons. This being the case, it would be expected that different types of serotonergic neurons innervate nociceptive and non-nociceptive spinal neurons. In order to test this hypothesis, a group of cells that include nociceptive neurons (spinothalamic tract neurons) and a group of predominantly non-nociceptive neurons (postsynaptic dorsal column neurons) in the spinal cord of rat were retrogradely labeled. Sections of the spinal cord containing retrogradely labeled spinothalamic tract or postsynaptic dorsal column neurons were stained for serotonin and either substance P or thyrotropin-releasing hormone using two-color immunohistochemistry. A retrogradely labeled cell was classified as \"apposed\" if there was no discernible distance between an immunohistochemically labeled varicosity and the cell. Eighty per cent of spinothalamic tract and 83% of postsynaptic dorsal column profiles were apposed by serotonin-immunoreactive varicosities in the spinal cord. Thirty-one per cent of the spinothalamic tract profiles that were apposed by serotonergic varicosities were apposed by serotonergic varicosities that were also stained for thyrotropin-releasing hormone. The distribution of the latter spinothalamic neurons was similar to that reported for spinothalamic tract neurons responsive to joint movement. In addition, at least 63% of the spinothalamic tract profiles which were apposed by serotonergic varicosities were apposed by \"serotonin-only\" varicosities, including most spinothalamic tract neurons in the marginal zone, suggesting that at least some \"serotonin-only\" neurons are antinociceptive. However, contrary to the hypothesis, at least 94% of the postsynaptic dorsal column profiles apposed by serotonergic varicosities were apposed by \"serotonin-only\" varicosities. These findings suggest that there may be a relationship between the sensory modality to which a spinal neuron responds and the type of serotonergic innervation it receives. However, it appears that \"serotonin-only\" neurons may not constitute a specifically antinociceptive category of serotonergic neurons.", "contents": "Organization of the serotonergic innervation of spinal neurons in rats--I. Neuropeptide coexistence in varicosities innervating some spinothalamic tract neurons but not in those innervating postsynaptic dorsal column neurons. Previous studies have suggested that peptides such as substance P and thyrotropin-releasing hormone coexist with serotonin in the same varicosities in the ventral horn and intermediate gray of the spinal cord in rat. However, coexistence of these peptides with serotonin is rare in fibers in the superficial dorsal horn. Since it has been proposed that serotonergic fibers in the superficial dorsal horn act to modulate nociception, it was hypothesized that the serotonergic neurons that contain neither substance P nor thyrotropin-releasing hormone might constitute a specifically antinociceptive subset of serotonergic neurons. This being the case, it would be expected that different types of serotonergic neurons innervate nociceptive and non-nociceptive spinal neurons. In order to test this hypothesis, a group of cells that include nociceptive neurons (spinothalamic tract neurons) and a group of predominantly non-nociceptive neurons (postsynaptic dorsal column neurons) in the spinal cord of rat were retrogradely labeled. Sections of the spinal cord containing retrogradely labeled spinothalamic tract or postsynaptic dorsal column neurons were stained for serotonin and either substance P or thyrotropin-releasing hormone using two-color immunohistochemistry. A retrogradely labeled cell was classified as \"apposed\" if there was no discernible distance between an immunohistochemically labeled varicosity and the cell. Eighty per cent of spinothalamic tract and 83% of postsynaptic dorsal column profiles were apposed by serotonin-immunoreactive varicosities in the spinal cord. Thirty-one per cent of the spinothalamic tract profiles that were apposed by serotonergic varicosities were apposed by serotonergic varicosities that were also stained for thyrotropin-releasing hormone. The distribution of the latter spinothalamic neurons was similar to that reported for spinothalamic tract neurons responsive to joint movement. In addition, at least 63% of the spinothalamic tract profiles which were apposed by serotonergic varicosities were apposed by \"serotonin-only\" varicosities, including most spinothalamic tract neurons in the marginal zone, suggesting that at least some \"serotonin-only\" neurons are antinociceptive. However, contrary to the hypothesis, at least 94% of the postsynaptic dorsal column profiles apposed by serotonergic varicosities were apposed by \"serotonin-only\" varicosities. These findings suggest that there may be a relationship between the sensory modality to which a spinal neuron responds and the type of serotonergic innervation it receives. However, it appears that \"serotonin-only\" neurons may not constitute a specifically antinociceptive category of serotonergic neurons."} {"id": "PMID:1280351", "title": "Charybdotoxin, dendrotoxin and mast cell degranulating peptide block the voltage-activated K+ current of fibroblast cells stably transfected with NGK1 (Kv1.2) K+ channel complementary DNA.", "content": "The blocking actions of the K+ channel toxins charybdotoxin, dendrotoxin and mast cell degranulating peptide were studied in B82 mouse fibroblast cells transformed to express NGK1 (Kv1.2) K+ channels. All three toxins were potent blockers of the K+ current in these cells, with KD values of 1.7, 2.8 and 185 nM, respectively. The toxin block exhibited a weak voltage-dependence with the degree of inhibition decreasing at positive membrane potentials. For charybdotoxin and dendrotoxin, reducing [K+]i did not increase the fractional block, demonstrating that the relief of block at positive membrane potentials is not due to displacement of the toxin molecules by outward flow of K+ ions. A voltage-jump protocol was used to determine the rates of binding and unbinding of dendrotoxin and mast cell degranulating peptide; binding of charybdotoxin was too rapid to be quantitatively evaluated in this manner. The binding rates (dendrotoxin, approximately 5 x 10(7)/M per s; mast cell degranulating peptide, approximately 0.8 x 10(7)/M per s) were largely voltage-independent, suggesting that association of the toxin molecules with the channel is diffusion limited. The rates of unbinding (dendrotoxin, approximately 0.3/s; mast cell degranulating peptide, approximately 3/s at +60 mV) of both toxins increased e-fold per approximately 40 mV change in membrane potential, thus accounting for the voltage-dependence of the equilibrium block. Internal perfusion with the three toxins failed to affect the K+ current (in contrast to internal tetraethylammonium which strongly blocked the current), indicating that the toxins exert their blocking action by binding to extracellular sites.", "contents": "Charybdotoxin, dendrotoxin and mast cell degranulating peptide block the voltage-activated K+ current of fibroblast cells stably transfected with NGK1 (Kv1.2) K+ channel complementary DNA. The blocking actions of the K+ channel toxins charybdotoxin, dendrotoxin and mast cell degranulating peptide were studied in B82 mouse fibroblast cells transformed to express NGK1 (Kv1.2) K+ channels. All three toxins were potent blockers of the K+ current in these cells, with KD values of 1.7, 2.8 and 185 nM, respectively. The toxin block exhibited a weak voltage-dependence with the degree of inhibition decreasing at positive membrane potentials. For charybdotoxin and dendrotoxin, reducing [K+]i did not increase the fractional block, demonstrating that the relief of block at positive membrane potentials is not due to displacement of the toxin molecules by outward flow of K+ ions. A voltage-jump protocol was used to determine the rates of binding and unbinding of dendrotoxin and mast cell degranulating peptide; binding of charybdotoxin was too rapid to be quantitatively evaluated in this manner. The binding rates (dendrotoxin, approximately 5 x 10(7)/M per s; mast cell degranulating peptide, approximately 0.8 x 10(7)/M per s) were largely voltage-independent, suggesting that association of the toxin molecules with the channel is diffusion limited. The rates of unbinding (dendrotoxin, approximately 0.3/s; mast cell degranulating peptide, approximately 3/s at +60 mV) of both toxins increased e-fold per approximately 40 mV change in membrane potential, thus accounting for the voltage-dependence of the equilibrium block. Internal perfusion with the three toxins failed to affect the K+ current (in contrast to internal tetraethylammonium which strongly blocked the current), indicating that the toxins exert their blocking action by binding to extracellular sites."} {"id": "PMID:1280352", "title": "Rapid neural growth: calcitonin gene-related peptide and substance P-containing nerves attain exceptional growth rates in regenerating deer antler.", "content": "Deer antler is a unique mineralized tissue which can produce very high growth rates of > 1 cm/day in large species. On completion of antler growth, the dermal tissues which cover the antler are shed and the underlying calcified tissue dies. After several months the old antler is discarded and growth of a new one begins. It is known that deer antlers are sensitive to touch and are innervated. The major aims of this study were to identify and localize by immunohistochemical techniques the type of innervation present, and to find out whether nerve fibres could exhibit growth rates comparable to those of antler. We have taken tissue sections from the tip and shaft of growing Red deer (Cervus elaphus) antlers at three stages of development; shortly after the initiation of regrowth, the rapid growth phase, and near the end of growth. Incubation of tissue sections with antisera to protein gene product 9.5 (a neural cytoplasmic protein), neurofilament triplet proteins (a neural cytoskeletal protein), substance P and calcitonin gene-related peptide (both of which are present in and synthesized by sensory neurons) showed the presence of immunoreactive nerve fibres in dermal, deep connective and perichondrial/periosteal tissues at all stages of antler growth. The sparse distribution of vasoactive intestinal polypeptide-like immunoreactivity was found in dermal tissue only at the earliest stage of antler development. Nerve fibres immunoreactive to neuropeptide Y, C-flanking peptide of neuropeptide Y and tyrosine hydroxylase, all present in postganglionic sympathetic nerves, were not observed at any stage of antler growth. Nerves expressing immunoreactivity for any of the neural markers or peptides employed could not be found in cartilage, osteoid or bone. These results show that antlers are innervated mainly by sensory nerves and that nerves can attain the exceptionally high growth rates found in regenerating antler.", "contents": "Rapid neural growth: calcitonin gene-related peptide and substance P-containing nerves attain exceptional growth rates in regenerating deer antler. Deer antler is a unique mineralized tissue which can produce very high growth rates of > 1 cm/day in large species. On completion of antler growth, the dermal tissues which cover the antler are shed and the underlying calcified tissue dies. After several months the old antler is discarded and growth of a new one begins. It is known that deer antlers are sensitive to touch and are innervated. The major aims of this study were to identify and localize by immunohistochemical techniques the type of innervation present, and to find out whether nerve fibres could exhibit growth rates comparable to those of antler. We have taken tissue sections from the tip and shaft of growing Red deer (Cervus elaphus) antlers at three stages of development; shortly after the initiation of regrowth, the rapid growth phase, and near the end of growth. Incubation of tissue sections with antisera to protein gene product 9.5 (a neural cytoplasmic protein), neurofilament triplet proteins (a neural cytoskeletal protein), substance P and calcitonin gene-related peptide (both of which are present in and synthesized by sensory neurons) showed the presence of immunoreactive nerve fibres in dermal, deep connective and perichondrial/periosteal tissues at all stages of antler growth. The sparse distribution of vasoactive intestinal polypeptide-like immunoreactivity was found in dermal tissue only at the earliest stage of antler development. Nerve fibres immunoreactive to neuropeptide Y, C-flanking peptide of neuropeptide Y and tyrosine hydroxylase, all present in postganglionic sympathetic nerves, were not observed at any stage of antler growth. Nerves expressing immunoreactivity for any of the neural markers or peptides employed could not be found in cartilage, osteoid or bone. These results show that antlers are innervated mainly by sensory nerves and that nerves can attain the exceptionally high growth rates found in regenerating antler."} {"id": "PMID:1280353", "title": "Abnormal labor and infant brain damage.", "content": "To determine whether arrest disorders result in increased neurologic abnormalities in infancy or childhood. Four hundred thirteen infants with arrest disorders as defined by Friedman criteria were matched to a similar population without arrest disorders. The median length of follow-up was 6 years for the study infants and 5.07 years for the controls. The numbers of children with abnormalities in the groups with and without arrest disorders, as well as the specific abnormalities encountered, were stratified by method of delivery. Thirty neurologic abnormalities were found in the arrest group and 37 in the control group; thus, the null hypotheses could not be rejected. In addition, although the control group was not followed as long as the study population, the diagnosis of abnormalities was more frequent in the later years in the controls. This suggests that had the follow-ups been equal, there would have been stronger proof that arrest by itself was not associated with infant brain damage. Our study confirms that labor diagnoses of prolonged active phase, protractions or arrests, and failure to descend are not associated with increased neurologic abnormalities. Delivery by cesarean or vaginal birth and use of oxytocin are not factors in the etiology of major brain damage.", "contents": "Abnormal labor and infant brain damage. To determine whether arrest disorders result in increased neurologic abnormalities in infancy or childhood. Four hundred thirteen infants with arrest disorders as defined by Friedman criteria were matched to a similar population without arrest disorders. The median length of follow-up was 6 years for the study infants and 5.07 years for the controls. The numbers of children with abnormalities in the groups with and without arrest disorders, as well as the specific abnormalities encountered, were stratified by method of delivery. Thirty neurologic abnormalities were found in the arrest group and 37 in the control group; thus, the null hypotheses could not be rejected. In addition, although the control group was not followed as long as the study population, the diagnosis of abnormalities was more frequent in the later years in the controls. This suggests that had the follow-ups been equal, there would have been stronger proof that arrest by itself was not associated with infant brain damage. Our study confirms that labor diagnoses of prolonged active phase, protractions or arrests, and failure to descend are not associated with increased neurologic abnormalities. Delivery by cesarean or vaginal birth and use of oxytocin are not factors in the etiology of major brain damage."} {"id": "PMID:1280354", "title": "Diagnostic possibilities of ERA in developmental speech disorders.", "content": "The differential diagnosis of developmental speech disorders may be very difficult. We tried to differentiate between the developmental dysphasia and dysarthria by means of CERA, using the different kinds of stimuli--tone bursts, words and white noise. The BERA was performed using the filtered clicks as stimuli. We have found the responses to tone, verbal and noise stimuli in children with developmental dysarthria. The latency times were prolonged to verbal and noise stimuli. We did not find any responses to verbal and noise stimuli in children with developmental dysphasia. At the BERA investigation we did not find the auditory evoked brainstem responses in children with developmental dysarthria on the side of motoric innervation lesion. The latency times of waves N3 and N5 were prolonged in children with developmental dysphasia. The CERA and BERA seems to be a good differential diagnostic tool for differentiation between these two kinds of developmental speech disorders. The results confirmed also that there are the mixed forms of those developmental speech disorders.", "contents": "Diagnostic possibilities of ERA in developmental speech disorders. The differential diagnosis of developmental speech disorders may be very difficult. We tried to differentiate between the developmental dysphasia and dysarthria by means of CERA, using the different kinds of stimuli--tone bursts, words and white noise. The BERA was performed using the filtered clicks as stimuli. We have found the responses to tone, verbal and noise stimuli in children with developmental dysarthria. The latency times were prolonged to verbal and noise stimuli. We did not find any responses to verbal and noise stimuli in children with developmental dysphasia. At the BERA investigation we did not find the auditory evoked brainstem responses in children with developmental dysarthria on the side of motoric innervation lesion. The latency times of waves N3 and N5 were prolonged in children with developmental dysphasia. The CERA and BERA seems to be a good differential diagnostic tool for differentiation between these two kinds of developmental speech disorders. The results confirmed also that there are the mixed forms of those developmental speech disorders."} {"id": "PMID:1280355", "title": "Quantitative image analysis of angiogenesis in rats implanted with a fibrin gel chamber.", "content": "Angiogenesis, a fundamental process in various physiological and pathological events, is generally studied using in vivo models, such as the chick chorioallantoic membrane or the rabbit cornea, which are difficult to quantitate. We developed the quantitation of angiogenesis in an in vivo model previously described by Dvorak et al [6]. Perforated plexiglass chambers filled with human or rat fibrin were implanted into the dorsal subcutaneous space of a Wistar rat. After four days of implantation, a sequentially organized invasion of the fibrin gel by various blood cell types occurred through the holes and neovascularized granulation tissue buds appeared. These buds presented mature neovessels and a new collagen matrix. Three dimensional computer image analysis of the chambers was performed using macroscopic and microscopic parameters: total vascularized area, bud height and equivalent diameter, number of vessels per bud and percentage of central vessels. The time course of the angiogenic response to rat or human fibrin gel was studied and 14 days was found to be the optimum period of implantation. The bud height and number of neovessels were not found to be significantly different when rat or human fibrin gels were used. This quantitative study was a prerequisite for further investigations of the effects of biological and pharmacological agents on angiogenesis.", "contents": "Quantitative image analysis of angiogenesis in rats implanted with a fibrin gel chamber. Angiogenesis, a fundamental process in various physiological and pathological events, is generally studied using in vivo models, such as the chick chorioallantoic membrane or the rabbit cornea, which are difficult to quantitate. We developed the quantitation of angiogenesis in an in vivo model previously described by Dvorak et al [6]. Perforated plexiglass chambers filled with human or rat fibrin were implanted into the dorsal subcutaneous space of a Wistar rat. After four days of implantation, a sequentially organized invasion of the fibrin gel by various blood cell types occurred through the holes and neovascularized granulation tissue buds appeared. These buds presented mature neovessels and a new collagen matrix. Three dimensional computer image analysis of the chambers was performed using macroscopic and microscopic parameters: total vascularized area, bud height and equivalent diameter, number of vessels per bud and percentage of central vessels. The time course of the angiogenic response to rat or human fibrin gel was studied and 14 days was found to be the optimum period of implantation. The bud height and number of neovessels were not found to be significantly different when rat or human fibrin gels were used. This quantitative study was a prerequisite for further investigations of the effects of biological and pharmacological agents on angiogenesis."} {"id": "PMID:1280356", "title": "Prognostic factors in invasive cervical carcinomas associated with human papillomavirus (HPV). Quantitative data and cytokeratin expression.", "content": "As a part of a larger programme to search for the prognostic factors in cervical cancer, quantitative morphometry, demonstration of AgNORs and expression of different cytokeratin polypeptides (SK2-27, SK1, A 53-B/A2) were used to study a series of 85 cervical squamous cell carcinomas, previously analysed for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction (PCR). The following nuclear profile parameters were calculated: nuclear area, perimeter, maximum diameter, ellipsoidity (form Ell), regularity (form Ar) and roundness (form Pe). In each case, the number of small (< 3 microns), large (> 3 microns), the total number and the ratio large/small AgNORs were registered. The cancer cell density and the lymphoid cell density were assessed. In the survival analysis, neither the expression of different cytokeratin polypeptides or the pattern of cytokeratin staining proved to be an independent variable. Similarly, none of the nuclear profile parameters analysed possessed an independent prognostic value in the survival analysis. The ratio of large/small AgNORs proved to be a significant independent prognostic predictor (p = 0.0104), second only to the lymphoid cell density. Also the total number of AgNORs was a prognostic indicator. This suggests that AgNOR size and ratio reflect tumor proliferation also in cervical squamous cell carcinoma, as shown in other human malignancies. Similarly, the density of cancer cell nuclei proved to be an independent prognostic predictor (p = 0.0601) in that the tumours in patients with longer survival showed lower density of the nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Prognostic factors in invasive cervical carcinomas associated with human papillomavirus (HPV). Quantitative data and cytokeratin expression. As a part of a larger programme to search for the prognostic factors in cervical cancer, quantitative morphometry, demonstration of AgNORs and expression of different cytokeratin polypeptides (SK2-27, SK1, A 53-B/A2) were used to study a series of 85 cervical squamous cell carcinomas, previously analysed for the presence of human papillomavirus (HPV) DNA by in situ hybridization and polymerase chain reaction (PCR). The following nuclear profile parameters were calculated: nuclear area, perimeter, maximum diameter, ellipsoidity (form Ell), regularity (form Ar) and roundness (form Pe). In each case, the number of small (< 3 microns), large (> 3 microns), the total number and the ratio large/small AgNORs were registered. The cancer cell density and the lymphoid cell density were assessed. In the survival analysis, neither the expression of different cytokeratin polypeptides or the pattern of cytokeratin staining proved to be an independent variable. Similarly, none of the nuclear profile parameters analysed possessed an independent prognostic value in the survival analysis. The ratio of large/small AgNORs proved to be a significant independent prognostic predictor (p = 0.0104), second only to the lymphoid cell density. Also the total number of AgNORs was a prognostic indicator. This suggests that AgNOR size and ratio reflect tumor proliferation also in cervical squamous cell carcinoma, as shown in other human malignancies. Similarly, the density of cancer cell nuclei proved to be an independent prognostic predictor (p = 0.0601) in that the tumours in patients with longer survival showed lower density of the nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280357", "title": "Expression of intermediate filaments in chordomas. An immunocytochemical study of five cases.", "content": "An immunocytochemical investigation has been carried out on five cases of chordoma (2 of the sacrum, 2 in the spheno-occipital bone and 1 in the parapharyngeal area) to study the expression of the 5 classes of intermediate filaments (IF): cytokeratin (CK), desmin (DES), GFAP, neurofilaments (NF) and vimentin (VIM). Our results show that constant coexpression of CK, NF and VIM does occur in chordomas, whereas DES and GFAP are not demonstrable in tumor cells. The three detected IF are invariably present in all cell types but not in intracellular vacuoles or in the extracellular mucoid substance. The pattern of immunoreactivity of chordomas appears very unique as very few other neoplasms demonstrate the simultaneous occurrence of 3 distinct IF. Only choroid plexus tumors have been shown to manifest CK-NF-VIM immunoreactivity. The complex immunophenotype of chordomas may be related to their supposed origin from the notochord which normally undergoes conspicuous changes in location and morphology during embryonal development. Such changes might require the contemporary presence of multiple IF; IF expression, in fact, is known to be related to cell function and morphology. Notochordal cells and their neoplastic counterpart may consequently express an IF pattern which reflects unique architectural and morphological variations occurring during embryonal and tumor growth. Together with the speculative value of the detection of CK, NF and VIM in chordomas, the unusual immunocytochemical pattern of these tumors might provide useful diagnostic tool in differential diagnosis.", "contents": "Expression of intermediate filaments in chordomas. An immunocytochemical study of five cases. An immunocytochemical investigation has been carried out on five cases of chordoma (2 of the sacrum, 2 in the spheno-occipital bone and 1 in the parapharyngeal area) to study the expression of the 5 classes of intermediate filaments (IF): cytokeratin (CK), desmin (DES), GFAP, neurofilaments (NF) and vimentin (VIM). Our results show that constant coexpression of CK, NF and VIM does occur in chordomas, whereas DES and GFAP are not demonstrable in tumor cells. The three detected IF are invariably present in all cell types but not in intracellular vacuoles or in the extracellular mucoid substance. The pattern of immunoreactivity of chordomas appears very unique as very few other neoplasms demonstrate the simultaneous occurrence of 3 distinct IF. Only choroid plexus tumors have been shown to manifest CK-NF-VIM immunoreactivity. The complex immunophenotype of chordomas may be related to their supposed origin from the notochord which normally undergoes conspicuous changes in location and morphology during embryonal development. Such changes might require the contemporary presence of multiple IF; IF expression, in fact, is known to be related to cell function and morphology. Notochordal cells and their neoplastic counterpart may consequently express an IF pattern which reflects unique architectural and morphological variations occurring during embryonal and tumor growth. Together with the speculative value of the detection of CK, NF and VIM in chordomas, the unusual immunocytochemical pattern of these tumors might provide useful diagnostic tool in differential diagnosis."} {"id": "PMID:1280358", "title": "Malignant fibrous histiocytoma of the pulmonary vein with prolapse through the mitral valve orifice.", "content": "We present the case of a 33 year old white woman with malignant fibrous histiocytoma arising from the pulmonary vein and prolapsing through the mitral valve, causing acute heart failure. The patient underwent emergency cardiothoracic surgery with resection of the tumour while on cardiopulmonary bypass. The patient's heart failure improved immediately following the resection, demonstrating the benefit of palliative surgery. Adjuvant chemotherapy was recommended and the patient did well for 18 months of follow-up.", "contents": "Malignant fibrous histiocytoma of the pulmonary vein with prolapse through the mitral valve orifice. We present the case of a 33 year old white woman with malignant fibrous histiocytoma arising from the pulmonary vein and prolapsing through the mitral valve, causing acute heart failure. The patient underwent emergency cardiothoracic surgery with resection of the tumour while on cardiopulmonary bypass. The patient's heart failure improved immediately following the resection, demonstrating the benefit of palliative surgery. Adjuvant chemotherapy was recommended and the patient did well for 18 months of follow-up."} {"id": "PMID:1280359", "title": "Acute and subacute effects of doxorubicin on postextrasystolic potentiation in guinea pig papillary muscles.", "content": "To investigate the effects of doxorubicin on postextrasystolic potentiation (PESP), isolated guinea pig papillary muscles were field-stimulated and the resulting isometric force was recorded. Postextrasystolic contraction was evoked following trains of 37 regular stimulations. The effects of acute doses of doxorubicin (0.2 mM) on regular contractions and postextrasystolic contractions were examined for 2 hr. The effects of subacute doses of doxorubicin (total dose 5 mg/kg intraperitoneally) on the relationship between %PESP (postextrasystolic/regular contraction) and both the extra-stimulus coupling interval and the postextrasystolic interval were examined. Acute administration of doxorubicin decreased the amplitude of postextrasystolic contractions more than that of regular contractions. Thus, %PESP in the doxorubicin-treated group decreased significantly over time. There was no similar decrease in the control papillary muscles. Both the extra-stimulus coupling interval and the postextrasystolic interval had less of an effect on %PESP in doxorubicin-treated animals than in control animals. Since PESP depends upon sarcoplasmic reticulum activity, our results indicate that acute and subacute exposure to doxorubicin impairs the activity of the sarcoplasmic reticulum of guinea pig papillary muscles.", "contents": "Acute and subacute effects of doxorubicin on postextrasystolic potentiation in guinea pig papillary muscles. To investigate the effects of doxorubicin on postextrasystolic potentiation (PESP), isolated guinea pig papillary muscles were field-stimulated and the resulting isometric force was recorded. Postextrasystolic contraction was evoked following trains of 37 regular stimulations. The effects of acute doses of doxorubicin (0.2 mM) on regular contractions and postextrasystolic contractions were examined for 2 hr. The effects of subacute doses of doxorubicin (total dose 5 mg/kg intraperitoneally) on the relationship between %PESP (postextrasystolic/regular contraction) and both the extra-stimulus coupling interval and the postextrasystolic interval were examined. Acute administration of doxorubicin decreased the amplitude of postextrasystolic contractions more than that of regular contractions. Thus, %PESP in the doxorubicin-treated group decreased significantly over time. There was no similar decrease in the control papillary muscles. Both the extra-stimulus coupling interval and the postextrasystolic interval had less of an effect on %PESP in doxorubicin-treated animals than in control animals. Since PESP depends upon sarcoplasmic reticulum activity, our results indicate that acute and subacute exposure to doxorubicin impairs the activity of the sarcoplasmic reticulum of guinea pig papillary muscles."} {"id": "PMID:1280360", "title": "Stimulatory and inhibitory effects of galanin on exocrine and endocrine rat pancreas.", "content": "The influence of the neuropeptide galanin, present in intrapancreatic nerve endings, on the endocrine pancreas is well known. The most potent effect of galanin is inhibition of insulin release. Little is known of its effect on the exocrine pancreas. Whether galanin plays a role in the regulation of exocrine pancreatic secretion and whether this effect is mediated directly on acinar cells or indirectly via the influence on insulin secretion is not clear. In the present study, we investigated these questions using the model of the isolated and arterially perfused rat pancreas with intact exocrine and endocrine secretion. In the presence of 15.8 mM glucose in a modified Krebs-Ringer buffer and during half-maximal stimulation of enzyme secretion with 100 pmol/ml cholecystokinin octapeptide (CCK-8), a dose-response study of 0.001-100 pmol/ml porcine galanin was performed. At concentrations of 0.001 and 0.01 pmol/ml, porcine galanin significantly stimulated insulin release (p < 0.05 and < 0.01, respectively) and also significantly enhanced CCK-8-stimulated amylase secretion (p < 0.05). Doses of 0.1 and 1 pmol/ml galanin resulted in a nonsignificant inhibition of insulin release, while 10 and 100 pmol/ml strongly inhibited the endocrine response (p < 0.001). However, concentration levels of 1-100 pmol/ml galanin did not affect CCK-8-stimulated amylase secretion. Rat galanin, tested at 0.01 and 10 pmol/ml, showed no significant difference from the effects of porcine galanin at the equipotent concentrations. It is concluded that the effect of galanin on exocrine pancreas, like the effect on endocrine functions, tends to be a direct one and that it could exert a modulatory influence on the level of neuronal transmission.", "contents": "Stimulatory and inhibitory effects of galanin on exocrine and endocrine rat pancreas. The influence of the neuropeptide galanin, present in intrapancreatic nerve endings, on the endocrine pancreas is well known. The most potent effect of galanin is inhibition of insulin release. Little is known of its effect on the exocrine pancreas. Whether galanin plays a role in the regulation of exocrine pancreatic secretion and whether this effect is mediated directly on acinar cells or indirectly via the influence on insulin secretion is not clear. In the present study, we investigated these questions using the model of the isolated and arterially perfused rat pancreas with intact exocrine and endocrine secretion. In the presence of 15.8 mM glucose in a modified Krebs-Ringer buffer and during half-maximal stimulation of enzyme secretion with 100 pmol/ml cholecystokinin octapeptide (CCK-8), a dose-response study of 0.001-100 pmol/ml porcine galanin was performed. At concentrations of 0.001 and 0.01 pmol/ml, porcine galanin significantly stimulated insulin release (p < 0.05 and < 0.01, respectively) and also significantly enhanced CCK-8-stimulated amylase secretion (p < 0.05). Doses of 0.1 and 1 pmol/ml galanin resulted in a nonsignificant inhibition of insulin release, while 10 and 100 pmol/ml strongly inhibited the endocrine response (p < 0.001). However, concentration levels of 1-100 pmol/ml galanin did not affect CCK-8-stimulated amylase secretion. Rat galanin, tested at 0.01 and 10 pmol/ml, showed no significant difference from the effects of porcine galanin at the equipotent concentrations. It is concluded that the effect of galanin on exocrine pancreas, like the effect on endocrine functions, tends to be a direct one and that it could exert a modulatory influence on the level of neuronal transmission."} {"id": "PMID:1280361", "title": "Pancreatic galanin: molecular forms and anatomical locations.", "content": "Galanin-like immunoreactivity (GalLI) was found to be present in extracts taken from human, canine, and porcine pancreata. The dominant gel filtration peak in each species co-elutes with standard synthetic porcine galanin (Gal), but an apparently smaller molecular weight Gal form was present in human pancreas and intestine and in dog intestine. Reverse-phase HPLC demonstrated identity of porcine pancreatic Gal immunoreactivity with synthetic intestinal Gal. Heterogeneity was seen on reverse-phase HPLC: Human pancreas and intestine had three peaks of immunoreactivity; the retention times were identical between the pancreas and intestinal extracts; and human Gal elutes at an earlier retention time than porcine Gal. Similarly, dog pancreatic GalLI eluted earlier than porcine Gal on reverse-phase HPLC. Immunohistochemical studies revealed the presence of specific staining for GalLI in varicose nerve fibers in the pancreas of the three species. In the dog pancreas an association between Gal-containing nerve fibers and islet cells was readily demonstrable. This was not the case with pig or human pancreas. We conclude that pancreatic Gal is present in the pancreas of the three species and that molecular heterogeneity is similar between intestinal and pancreatic forms. In the dog, a distinct anatomical relationship is demonstrable between Gal-containing nerves and islet cells.", "contents": "Pancreatic galanin: molecular forms and anatomical locations. Galanin-like immunoreactivity (GalLI) was found to be present in extracts taken from human, canine, and porcine pancreata. The dominant gel filtration peak in each species co-elutes with standard synthetic porcine galanin (Gal), but an apparently smaller molecular weight Gal form was present in human pancreas and intestine and in dog intestine. Reverse-phase HPLC demonstrated identity of porcine pancreatic Gal immunoreactivity with synthetic intestinal Gal. Heterogeneity was seen on reverse-phase HPLC: Human pancreas and intestine had three peaks of immunoreactivity; the retention times were identical between the pancreas and intestinal extracts; and human Gal elutes at an earlier retention time than porcine Gal. Similarly, dog pancreatic GalLI eluted earlier than porcine Gal on reverse-phase HPLC. Immunohistochemical studies revealed the presence of specific staining for GalLI in varicose nerve fibers in the pancreas of the three species. In the dog pancreas an association between Gal-containing nerve fibers and islet cells was readily demonstrable. This was not the case with pig or human pancreas. We conclude that pancreatic Gal is present in the pancreas of the three species and that molecular heterogeneity is similar between intestinal and pancreatic forms. In the dog, a distinct anatomical relationship is demonstrable between Gal-containing nerves and islet cells."} {"id": "PMID:1280362", "title": "Effects of galanin and norepinephrine on insulin secretion in the mouse.", "content": "Galanin and norepinephrine (NE) both occur in adrenergic nerves in the pancreas. Since they are co-released from the nerve terminals and both inhibit glucose-induced insulin release, we investigated in the mouse if they cooperate in exerting this effect. When administered alone in vivo, both galanin (50-530 pmol/kg) and NE (40-320 nmol/kg) dose-dependently inhibited the increase in plasma insulin levels at 1 min following intravenous injection of glucose (2.8 mmol/kg). When galanin and NE were given together at different dose levels, no potentiating effect on the inhibition of the glucose-induced plasma insulin response was observed. In vitro, in overnight cultured mouse islets, both galanin (10(-9)-10(-6) M) and NE (10(-9)-10(-6) M) in a dose-related manner inhibited the insulin release induced by 11.1 mM glucose. Galanin (10(-9) M) did not further enhance the inhibited insulin response evoked by NE (10(-9)-10(-6) M). Thus, no functional evidence exists, either in vivo or in vitro, that galanin and NE potentiate the inhibitory action of each other on glucose-induced insulin release in the mouse.", "contents": "Effects of galanin and norepinephrine on insulin secretion in the mouse. Galanin and norepinephrine (NE) both occur in adrenergic nerves in the pancreas. Since they are co-released from the nerve terminals and both inhibit glucose-induced insulin release, we investigated in the mouse if they cooperate in exerting this effect. When administered alone in vivo, both galanin (50-530 pmol/kg) and NE (40-320 nmol/kg) dose-dependently inhibited the increase in plasma insulin levels at 1 min following intravenous injection of glucose (2.8 mmol/kg). When galanin and NE were given together at different dose levels, no potentiating effect on the inhibition of the glucose-induced plasma insulin response was observed. In vitro, in overnight cultured mouse islets, both galanin (10(-9)-10(-6) M) and NE (10(-9)-10(-6) M) in a dose-related manner inhibited the insulin release induced by 11.1 mM glucose. Galanin (10(-9) M) did not further enhance the inhibited insulin response evoked by NE (10(-9)-10(-6) M). Thus, no functional evidence exists, either in vivo or in vitro, that galanin and NE potentiate the inhibitory action of each other on glucose-induced insulin release in the mouse."} {"id": "PMID:1280363", "title": "Qualitative and quantitative changes in islet cells of autotransplanted pancreas in dogs in relation to glucose metabolism.", "content": "This study was conducted to clarify the quantitative and qualitative changes in the cells of the islets of Langerhans in the autotransplanted pancreas in dogs and to correlate these changes with alterations of glucose tolerance. The left lobe of a canine pancreas was transplanted into the left iliac fossa. The splenic vessels were anastomosed to the left iliac vessels. The pancreatic duct was left open to the peritoneal cavity. Open biopsies of the autotransplanted pancreas were performed 3, 7, 11, and 14 weeks after transplantation. The islets in the transplanted pancreas were examined ultrastructurally; B-cells, A-cells, and D-cells were identified immunohistochemically and their percentages were determined. Intravenous glucose tolerance tests were performed 3, 5, 7, 11, and 14 weeks after operation, and several indexes (K values and integrated response and increased values for baseline serum and immunoreactive insulin) were calculated. Fibrosis of the transplanted pancreas progressed after transplantation. The percentage of B-cells fell significantly (p < 0.01), whereas that of A- and D-cells did not have significant changes. The ultrastructural study revealed an increase in collagen bundles, degranulation of B-cells, and marked preservation of A-cell granules 3 weeks after transplantation. B-Cells with dark cytoplasm were found 7 weeks after operation. In contrast, clusters of immature B-cells were seen in some sections of the pancreas 14 weeks after autotransplantation. The integrated response in baseline serum was increased significantly (p < 0.01), and the K value was decreased significantly (p < 0.01) 11 weeks after autotransplantation when compared with the initial posttransplant period.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Qualitative and quantitative changes in islet cells of autotransplanted pancreas in dogs in relation to glucose metabolism. This study was conducted to clarify the quantitative and qualitative changes in the cells of the islets of Langerhans in the autotransplanted pancreas in dogs and to correlate these changes with alterations of glucose tolerance. The left lobe of a canine pancreas was transplanted into the left iliac fossa. The splenic vessels were anastomosed to the left iliac vessels. The pancreatic duct was left open to the peritoneal cavity. Open biopsies of the autotransplanted pancreas were performed 3, 7, 11, and 14 weeks after transplantation. The islets in the transplanted pancreas were examined ultrastructurally; B-cells, A-cells, and D-cells were identified immunohistochemically and their percentages were determined. Intravenous glucose tolerance tests were performed 3, 5, 7, 11, and 14 weeks after operation, and several indexes (K values and integrated response and increased values for baseline serum and immunoreactive insulin) were calculated. Fibrosis of the transplanted pancreas progressed after transplantation. The percentage of B-cells fell significantly (p < 0.01), whereas that of A- and D-cells did not have significant changes. The ultrastructural study revealed an increase in collagen bundles, degranulation of B-cells, and marked preservation of A-cell granules 3 weeks after transplantation. B-Cells with dark cytoplasm were found 7 weeks after operation. In contrast, clusters of immature B-cells were seen in some sections of the pancreas 14 weeks after autotransplantation. The integrated response in baseline serum was increased significantly (p < 0.01), and the K value was decreased significantly (p < 0.01) 11 weeks after autotransplantation when compared with the initial posttransplant period.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280364", "title": "Effect of basic fibroblast growth factor on ornithine decarboxylase activity and mRNA expression in a pancreatic tumoral cell line (AR4-2J).", "content": "Basic fibroblast growth factor (bFGF) is a potent mitogen for various cell types. Induction of ornithine decarboxylase (ODC) activity is one of the early events triggered in proliferating cells. Our aim was to study the effect of bFGF on ODC activity and ODC mRNA expression in a pancreatic tumoral cell line, AR4-2J. Following kinetic and dose-response studies, we found that maximal stimulation (150% over control) of ODC activity occurred after 3 h of bFGF treatment (10(-9) M), the EC50 being 20 pM. To elucidate the mechanism by which bFGF stimulates ODC activity, we measured the ODC mRNA levels by Northern blot hybridization using a 32P-labeled rat cDNA probe. In AR4-2J cells treated with bFGF at 10(-9) M over 120 min, ODC mRNA expression was transiently increased by 71.6% at 60 min. Furthermore, bFGF was also able to stimulate ODC mRNA synthesis in the presence of cycloheximide. In conclusion, in AR4-2J cells of pancreatic origin, bFGF stimulates ODC gene transcription. This effect contributes to the stimulation of ODC enzymatic activity and to the proliferative effect of bFGF on this cell line.", "contents": "Effect of basic fibroblast growth factor on ornithine decarboxylase activity and mRNA expression in a pancreatic tumoral cell line (AR4-2J). Basic fibroblast growth factor (bFGF) is a potent mitogen for various cell types. Induction of ornithine decarboxylase (ODC) activity is one of the early events triggered in proliferating cells. Our aim was to study the effect of bFGF on ODC activity and ODC mRNA expression in a pancreatic tumoral cell line, AR4-2J. Following kinetic and dose-response studies, we found that maximal stimulation (150% over control) of ODC activity occurred after 3 h of bFGF treatment (10(-9) M), the EC50 being 20 pM. To elucidate the mechanism by which bFGF stimulates ODC activity, we measured the ODC mRNA levels by Northern blot hybridization using a 32P-labeled rat cDNA probe. In AR4-2J cells treated with bFGF at 10(-9) M over 120 min, ODC mRNA expression was transiently increased by 71.6% at 60 min. Furthermore, bFGF was also able to stimulate ODC mRNA synthesis in the presence of cycloheximide. In conclusion, in AR4-2J cells of pancreatic origin, bFGF stimulates ODC gene transcription. This effect contributes to the stimulation of ODC enzymatic activity and to the proliferative effect of bFGF on this cell line."} {"id": "PMID:1280365", "title": "Serum protease inhibitor capacity for elastase and the severity of pancreatitis.", "content": "To clarify the relationship between the diminution of the serum protease inhibitor capacity and the severity of pancreatitis, the binding capacity of serum protease inhibitors for exogenous elastase 1 (E1) was investigated by gel filtration, the elastase activity of the alpha 2-macroglobulin (alpha 2-M)-elastase complex was measured, and the relationship between these findings and the severity of pancreatitis was studied in 13 patients with pancreatic disease and 6 healthy subjects. When 125I-labeled E1 was added to the sera of healthy subjects, it bound to alpha 2-M and alpha 1-protease inhibitor (alpha 1-PI) with a mean ratio of 72:28. In mild acute pancreatitis (n = 5), the binding capacity of alpha 2-M was less than that in healthy subjects. In severe pancreatitis (n = 4), most of the exogenous E1 bound to alpha 1-PI (alpha 2-M vs. alpha 1-PI, 13:87). This diminution in the binding capacity of alpha 2-M correlated well with the severity of acute pancreatitis. In the sera of patients (n = 4) with pancreatic cancer containing much immunoreactive E1, the proportion of exogenous E1 bound by alpha 2-M and alpha 1-PI (25:75) was similar to that seen in severe acute pancreatitis. A significant inverse relationship between the binding capacity of alpha 2-M and the activity of the endogenous elastase bound to alpha 2-M was seen in various pancreatic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Serum protease inhibitor capacity for elastase and the severity of pancreatitis. To clarify the relationship between the diminution of the serum protease inhibitor capacity and the severity of pancreatitis, the binding capacity of serum protease inhibitors for exogenous elastase 1 (E1) was investigated by gel filtration, the elastase activity of the alpha 2-macroglobulin (alpha 2-M)-elastase complex was measured, and the relationship between these findings and the severity of pancreatitis was studied in 13 patients with pancreatic disease and 6 healthy subjects. When 125I-labeled E1 was added to the sera of healthy subjects, it bound to alpha 2-M and alpha 1-protease inhibitor (alpha 1-PI) with a mean ratio of 72:28. In mild acute pancreatitis (n = 5), the binding capacity of alpha 2-M was less than that in healthy subjects. In severe pancreatitis (n = 4), most of the exogenous E1 bound to alpha 1-PI (alpha 2-M vs. alpha 1-PI, 13:87). This diminution in the binding capacity of alpha 2-M correlated well with the severity of acute pancreatitis. In the sera of patients (n = 4) with pancreatic cancer containing much immunoreactive E1, the proportion of exogenous E1 bound by alpha 2-M and alpha 1-PI (25:75) was similar to that seen in severe acute pancreatitis. A significant inverse relationship between the binding capacity of alpha 2-M and the activity of the endogenous elastase bound to alpha 2-M was seen in various pancreatic diseases.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280366", "title": "Modulation of pancreatic exocrine function in rodents by treatment with pancreatic polypeptide.", "content": "The in vivo and in vitro treatment effects of pancreatic polypeptide (PP) were characterized by studying agonist-stimulated enzyme secretion in pancreatic acini prepared from 8-week-old mice treated for 2 days with PP (200 micrograms kg-1 day-1) and in pancreatic lobules from untreated male rats. In the mouse studies, enzyme secretion was evaluated on the basis of percentage total amylase released, amylase released per unit of DNA, and amylase released per unit of protein. When expressed as percentage total amylase released, the acini from mice treated with PP were significantly less responsive to pancreatic secretagogues than were acini from control animals. Chronic treatment with bovine PP lowered the maximal response to carbachol (12.3 +/- 0.3 vs. 9.0 +/- 0.3% total amylase release in control and PP treated, respectively), decreased the magnitude of the difference between basal and maximal amylase release (10.6 +/- 0.4 vs. 6.2 +/- 0.5% total amylase release in control and PP treated, respectively), and affected these changes without modifying the dose of carbachol producing half-maximal amylase release. Similarly, the percentage of total amylase released in response to all doses of cholecystokinin octapeptide (1-100 pM) was reduced by chronic treatment with PP. However, when amylase release was expressed relative to protein or DNA, no differences in enzyme release were detected between treatments with either secretagogue. Chronic treatment with PP increased the total amount of amylase in the acini (per unit DNA or protein), but the increased amylase appeared to be unavailable for release since the actual amount (per microgram DNA or milligram protein) released in response to agonists did not differ between treatments.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Modulation of pancreatic exocrine function in rodents by treatment with pancreatic polypeptide. The in vivo and in vitro treatment effects of pancreatic polypeptide (PP) were characterized by studying agonist-stimulated enzyme secretion in pancreatic acini prepared from 8-week-old mice treated for 2 days with PP (200 micrograms kg-1 day-1) and in pancreatic lobules from untreated male rats. In the mouse studies, enzyme secretion was evaluated on the basis of percentage total amylase released, amylase released per unit of DNA, and amylase released per unit of protein. When expressed as percentage total amylase released, the acini from mice treated with PP were significantly less responsive to pancreatic secretagogues than were acini from control animals. Chronic treatment with bovine PP lowered the maximal response to carbachol (12.3 +/- 0.3 vs. 9.0 +/- 0.3% total amylase release in control and PP treated, respectively), decreased the magnitude of the difference between basal and maximal amylase release (10.6 +/- 0.4 vs. 6.2 +/- 0.5% total amylase release in control and PP treated, respectively), and affected these changes without modifying the dose of carbachol producing half-maximal amylase release. Similarly, the percentage of total amylase released in response to all doses of cholecystokinin octapeptide (1-100 pM) was reduced by chronic treatment with PP. However, when amylase release was expressed relative to protein or DNA, no differences in enzyme release were detected between treatments with either secretagogue. Chronic treatment with PP increased the total amount of amylase in the acini (per unit DNA or protein), but the increased amylase appeared to be unavailable for release since the actual amount (per microgram DNA or milligram protein) released in response to agonists did not differ between treatments.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280367", "title": "Bioactivation of free-fat transfers: a potential new approach to improving graft survival.", "content": "A new approach to free-fat autotransplantation resorption was evaluated experimentally in a rat animal model. Bioactive fat grafts were created by the addition of basic fibroblast growth factor delivered by dextran beads to the grafts and compared with free fat alone, free fat plus beads, and free fat plus beads and a control solution in the same animal. The grafts were assessed by weight and histology at 1 and 12 months postoperatively in 40 animals. A graded response in weight retention was observed at 1 and 12 months, with the growth factor-treated grafts exhibiting near complete weight maintenance after 1 year. All other bead-containing grafts had an intermediate response, with free fat alone averaging more than one-half graft weight loss after 1 year. Histologically, the bead-containing grafts had good fibroblastic ingrowth, but extensive intercellular collagen formation and the occurrence of small-sized adipocytes among the larger adipocytes were seen only in the growth factor-treated grafts. These findings indicate that graft manipulations that affect the preadipocyte cells of the graft or fibroblastic components of the recipient site, either through polypeptide stimulation or surface charge attraction, may offer a viable approach to postoperative fat-graft volume maintenance.", "contents": "Bioactivation of free-fat transfers: a potential new approach to improving graft survival. A new approach to free-fat autotransplantation resorption was evaluated experimentally in a rat animal model. Bioactive fat grafts were created by the addition of basic fibroblast growth factor delivered by dextran beads to the grafts and compared with free fat alone, free fat plus beads, and free fat plus beads and a control solution in the same animal. The grafts were assessed by weight and histology at 1 and 12 months postoperatively in 40 animals. A graded response in weight retention was observed at 1 and 12 months, with the growth factor-treated grafts exhibiting near complete weight maintenance after 1 year. All other bead-containing grafts had an intermediate response, with free fat alone averaging more than one-half graft weight loss after 1 year. Histologically, the bead-containing grafts had good fibroblastic ingrowth, but extensive intercellular collagen formation and the occurrence of small-sized adipocytes among the larger adipocytes were seen only in the growth factor-treated grafts. These findings indicate that graft manipulations that affect the preadipocyte cells of the graft or fibroblastic components of the recipient site, either through polypeptide stimulation or surface charge attraction, may offer a viable approach to postoperative fat-graft volume maintenance."} {"id": "PMID:1280368", "title": "Study of functional and biochemical indicators of subclinical lung damage in bleomycin-treated patients.", "content": "In 30 patients affected by testicular non-seminomatous cancer we evaluated pulmonary function tests before and after bleomycin-including combination chemotherapy. We paid particular attention to changes in diffusing lung capacity (DCO) and its two components, namely diffusing capacity of the alveolar-capillary membrane (Dm) and pulmonary capillary blood volume (Vc). In the same patients we also evaluated the behaviour of serum procollagen III aminopeptide (sP-III-P), assumed to be a biochemical equivalent to Dm, and of serum angiotensin converting enzyme (S-ACE), assumed to be a biochemical equivalent to Vc. We found that, after chemotherapy, patients showed a significant decline in several pulmonary function parameters, namely VC, TLC, and FEV1 (P < 0.0001, P = 0.0351, P = 0.0004, respectively), when compared to pre-treatment values. DCO was significantly impaired after chemotherapy (P < 0.0001), but with regard to its components, Vc values showed a significant decline (P = 0.0002), whereas Dm values were unchanged. Values of sP-III-P raised significantly after chemotherapy (P = 0.003), whereas S-ACE activity did not show any significant variation. When we looked at relationships between functional and biochemical parameter variations, the only significant correlation we found was between DCO and S-ACE (r2 = 0.112; P < 0.02). We conclude that in asymptomatic patients treated by bleomycin-including combination chemotherapy, DCO impairment is likely to occur because of a subclinical injury to pulmonary vessels, as suggested by Vc decline. Although the occurrence of pulmonary interstitial fibrosis after chemotherapy was excluded by chest X-ray examination and by stable values of Dm, sP-III-P elevation would suggest an accelerated type III collagen turnover in interstitial fibroblasts activated by bleomycin.", "contents": "Study of functional and biochemical indicators of subclinical lung damage in bleomycin-treated patients. In 30 patients affected by testicular non-seminomatous cancer we evaluated pulmonary function tests before and after bleomycin-including combination chemotherapy. We paid particular attention to changes in diffusing lung capacity (DCO) and its two components, namely diffusing capacity of the alveolar-capillary membrane (Dm) and pulmonary capillary blood volume (Vc). In the same patients we also evaluated the behaviour of serum procollagen III aminopeptide (sP-III-P), assumed to be a biochemical equivalent to Dm, and of serum angiotensin converting enzyme (S-ACE), assumed to be a biochemical equivalent to Vc. We found that, after chemotherapy, patients showed a significant decline in several pulmonary function parameters, namely VC, TLC, and FEV1 (P < 0.0001, P = 0.0351, P = 0.0004, respectively), when compared to pre-treatment values. DCO was significantly impaired after chemotherapy (P < 0.0001), but with regard to its components, Vc values showed a significant decline (P = 0.0002), whereas Dm values were unchanged. Values of sP-III-P raised significantly after chemotherapy (P = 0.003), whereas S-ACE activity did not show any significant variation. When we looked at relationships between functional and biochemical parameter variations, the only significant correlation we found was between DCO and S-ACE (r2 = 0.112; P < 0.02). We conclude that in asymptomatic patients treated by bleomycin-including combination chemotherapy, DCO impairment is likely to occur because of a subclinical injury to pulmonary vessels, as suggested by Vc decline. Although the occurrence of pulmonary interstitial fibrosis after chemotherapy was excluded by chest X-ray examination and by stable values of Dm, sP-III-P elevation would suggest an accelerated type III collagen turnover in interstitial fibroblasts activated by bleomycin."} {"id": "PMID:1280370", "title": "[Expression of adhesion molecules N.CAM, L1 and HNK1 epitope by medulloblastoma].", "content": "Twelve medulloblastomas were screened for their expression of adhesion molecules L1, N.CAM isoforms and HNK1 epitope by Western blotting and immunohistochemistry. Highly sialylated N.CAM isoforms were distinguished from total N.CAMs by using a monoclonal antibody (anti-MenB) specifically recognizing high polymers of 2-8 linked neuraminic acid. All tumors expressed HNK1 epitope, N.CAM and its highly sialylated isoforms on their surface membrane. L1 adhesion molecule was detected by immunohistochemistry in only one medulloblastoma. This spectrum of expression of cell surface adhesion molecules distinguishes medulloblastomas from other primitive neuroectodermal tumors. Medulloblastomas share some immunological features with post-mitotic cells forming the external granular layer of the cerebellum. Western blotting analysis of cerebrospinal fluid (CSF) samples with anti-MenB antibody enabled us to detect highly sialylated N.CAM in some samples. The presence of this antigen in CSF appears to correlate with meningeal spreading of medulloblastomas and could help monitoring chemotherapeutic treatment.", "contents": "[Expression of adhesion molecules N.CAM, L1 and HNK1 epitope by medulloblastoma]. Twelve medulloblastomas were screened for their expression of adhesion molecules L1, N.CAM isoforms and HNK1 epitope by Western blotting and immunohistochemistry. Highly sialylated N.CAM isoforms were distinguished from total N.CAMs by using a monoclonal antibody (anti-MenB) specifically recognizing high polymers of 2-8 linked neuraminic acid. All tumors expressed HNK1 epitope, N.CAM and its highly sialylated isoforms on their surface membrane. L1 adhesion molecule was detected by immunohistochemistry in only one medulloblastoma. This spectrum of expression of cell surface adhesion molecules distinguishes medulloblastomas from other primitive neuroectodermal tumors. Medulloblastomas share some immunological features with post-mitotic cells forming the external granular layer of the cerebellum. Western blotting analysis of cerebrospinal fluid (CSF) samples with anti-MenB antibody enabled us to detect highly sialylated N.CAM in some samples. The presence of this antigen in CSF appears to correlate with meningeal spreading of medulloblastomas and could help monitoring chemotherapeutic treatment."} {"id": "PMID:1280371", "title": "Pathogenesis of central nervous system paraneoplastic syndromes.", "content": "The pathogenesis of central nervous system paraneoplastic syndromes has not been established. Increasing evidence supports the hypothesis that CNS paraneoplastic syndromes are immune disorders arising from an immune response to the underlying neoplasm. The hypothesis is that antigens or epitopes shared between the tumor and the nervous system are recognized as foreign by the host and elicit an immune response. The immune response is directed appropriately against the tumor leading to a more indolent course in those patients with paraneoplastic syndromes but is misdirected against the nervous system often leading to severe nervous system destruction. The evidence for this hypothesis consists of: 1) The finding of high titer autoantibodies that react with antigens in both tumor and central nervous system. 2) Intrathecal synthesis of the antibody. 3) The presence of the antibody in the central nervous system at autopsy. The development of animal models will be required to determine the exact nature of the pathogenesis of these disorders.", "contents": "Pathogenesis of central nervous system paraneoplastic syndromes. The pathogenesis of central nervous system paraneoplastic syndromes has not been established. Increasing evidence supports the hypothesis that CNS paraneoplastic syndromes are immune disorders arising from an immune response to the underlying neoplasm. The hypothesis is that antigens or epitopes shared between the tumor and the nervous system are recognized as foreign by the host and elicit an immune response. The immune response is directed appropriately against the tumor leading to a more indolent course in those patients with paraneoplastic syndromes but is misdirected against the nervous system often leading to severe nervous system destruction. The evidence for this hypothesis consists of: 1) The finding of high titer autoantibodies that react with antigens in both tumor and central nervous system. 2) Intrathecal synthesis of the antibody. 3) The presence of the antibody in the central nervous system at autopsy. The development of animal models will be required to determine the exact nature of the pathogenesis of these disorders."} {"id": "PMID:1280372", "title": "Amniocentesis--still important in the management of severe rhesus incompatibility.", "content": "To determine the role of amniocentesis in the management of severe rhesus (Rh), incompatibility. A 10-year retrospective descriptive study. Department of Obstetrics and Gynaecology, Tygerberg Hospital, CP. 111 pregnancies complicated by severe Rh incompatibility where management had been based on results obtained from amniocentesis. Neonatal haemoglobin values, neonatal survival and short-term morbidity as compared with the position on the Liley chart after amniocentesis immediately before delivery. Average neonatal haemoglobin value decreased for the group in the lower zone through the midzone to the upper zone, but wide scattering of individual values between the various zones occurred. Perinatal mortality rate was 93/1,000 deliveries with Rh-related deaths occurring only in the upper midzone and upper zones. One death and 7 cases of morbidity occurred after acting on misleading information from the Liley curve. Amniotic fluid bilirubin values are at best an indirect evaluation of the state of disease. No serious complications are likely to occur when these values fall in the lower or lower mid-zones of the Liley chart. When bilirubin values fall in the upper midzone or upper zone, cordocentesis should be performed to prevent overreaction or to perform an intra-uterine transfusion.", "contents": "Amniocentesis--still important in the management of severe rhesus incompatibility. To determine the role of amniocentesis in the management of severe rhesus (Rh), incompatibility. A 10-year retrospective descriptive study. Department of Obstetrics and Gynaecology, Tygerberg Hospital, CP. 111 pregnancies complicated by severe Rh incompatibility where management had been based on results obtained from amniocentesis. Neonatal haemoglobin values, neonatal survival and short-term morbidity as compared with the position on the Liley chart after amniocentesis immediately before delivery. Average neonatal haemoglobin value decreased for the group in the lower zone through the midzone to the upper zone, but wide scattering of individual values between the various zones occurred. Perinatal mortality rate was 93/1,000 deliveries with Rh-related deaths occurring only in the upper midzone and upper zones. One death and 7 cases of morbidity occurred after acting on misleading information from the Liley curve. Amniotic fluid bilirubin values are at best an indirect evaluation of the state of disease. No serious complications are likely to occur when these values fall in the lower or lower mid-zones of the Liley chart. When bilirubin values fall in the upper midzone or upper zone, cordocentesis should be performed to prevent overreaction or to perform an intra-uterine transfusion."} {"id": "PMID:1280373", "title": "Cytotoxic effects of cyclosporin A on the exocrine pancreas in rats.", "content": "The current study was done to evaluate the subacute toxic effects of cyclosporin A (CS) on the exocrine pancreas and the protective effect of potent protease inhibitor camostate (FOY-305). CS administration (15 milligrams, twice a day) for 14 days caused a significant increase in serum amylase levels, pancreatic amylase and cathepsin B content and mild acinar cell vacuolization and interstitial edema. CS also caused the redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction, indicating colocalization of lysosomal enzyme with pancreatic digestive enzymes. The administration of camostate (150 milligrams per kilogram, twice a day for 14 days) almost completely prevented the toxic changes induced by CS. These results indicate that CS induces exocrine pancreatic injury and that lysosomal enzymes play important roles in the pathogenesis of the injury. The results also suggest the usefulness of camostate in protecting the exocrine pancreas in patients treated with CS after organ transplantation, because it can inhibit some proteases that are closely involved in the fragility of the subcellular organelles.", "contents": "Cytotoxic effects of cyclosporin A on the exocrine pancreas in rats. The current study was done to evaluate the subacute toxic effects of cyclosporin A (CS) on the exocrine pancreas and the protective effect of potent protease inhibitor camostate (FOY-305). CS administration (15 milligrams, twice a day) for 14 days caused a significant increase in serum amylase levels, pancreatic amylase and cathepsin B content and mild acinar cell vacuolization and interstitial edema. CS also caused the redistribution of cathepsin B activity from the lysosomal fraction to the zymogen fraction, indicating colocalization of lysosomal enzyme with pancreatic digestive enzymes. The administration of camostate (150 milligrams per kilogram, twice a day for 14 days) almost completely prevented the toxic changes induced by CS. These results indicate that CS induces exocrine pancreatic injury and that lysosomal enzymes play important roles in the pathogenesis of the injury. The results also suggest the usefulness of camostate in protecting the exocrine pancreas in patients treated with CS after organ transplantation, because it can inhibit some proteases that are closely involved in the fragility of the subcellular organelles."} {"id": "PMID:1280374", "title": "Current management of hilar cholangiocarcinoma.", "content": "The goal in the treatment of hilar cholangiocarcinoma is the relief of biliary obstruction with the quality survival. The choice of therapy for an individual patient requires complete preoperative staging to determine the resectability. This is best accomplished in a multidisciplinary setting with radiologists, gastroenterologists and surgeons participating in the diagnostic and therapeutic strategies. Operative removal of the tumor can be performed with low mortality and, when possible, provides the longest palliation and offers potential for cure. For tumors found at operation to be unresectable, biliary enteric bypass provides a durable method of palliation. The relative merits of the newer methods of radiologic stenting are encouraging, but further study will require prospective trials in comparison to operative biliary enteric bypass.", "contents": "Current management of hilar cholangiocarcinoma. The goal in the treatment of hilar cholangiocarcinoma is the relief of biliary obstruction with the quality survival. The choice of therapy for an individual patient requires complete preoperative staging to determine the resectability. This is best accomplished in a multidisciplinary setting with radiologists, gastroenterologists and surgeons participating in the diagnostic and therapeutic strategies. Operative removal of the tumor can be performed with low mortality and, when possible, provides the longest palliation and offers potential for cure. For tumors found at operation to be unresectable, biliary enteric bypass provides a durable method of palliation. The relative merits of the newer methods of radiologic stenting are encouraging, but further study will require prospective trials in comparison to operative biliary enteric bypass."} {"id": "PMID:1280375", "title": "The interaction of botrocetin with normal or variant von Willebrand factor (types IIA and IIB) and its inhibition by monoclonal antibodies that block receptor binding.", "content": "We have recently shown the existence of two distinct forms of botrocetin (one-chain and two-chain), and demonstrated that the two-chain species is approximately 30 times more active than the one-chain in promoting von Willebrand factor (vWF) binding to platelet glycoprotein (GP) Ib. The N-terminal sequence of two-chain botrocetin is highly homologous to sea-urchin Echinoidin and other Ca(2+)-dependent lectins (Fujimura et al., Biochemistry 1991; 30: 1957-64). Present data indicate that purified two-chain botrocetin binds to vWF from plasmas of patients with type IIA or IIB von Willebrand disease and its interaction is indistinguishable from that with vWF from normal individuals. However, an \"activated complex\" formed between botrocetin and IIB vWF expresses an enhanced biological activity for binding to GP Ib whereas the complex with IIA vWF has a decreased binding activity. Among several anti-vWF monoclonal antibodies (MoAbs) which inhibit ristocetin-induced platelet aggregation and/or vWF binding to GP Ib, only two MoAbs (NMC-4 and RFF-VIII RAG:1) abolished direct binding between purified botrocetin and vWF. This suggests that they recognize an epitope(s) on the vWF molecule in close proximity to the botrocetin binding site.", "contents": "The interaction of botrocetin with normal or variant von Willebrand factor (types IIA and IIB) and its inhibition by monoclonal antibodies that block receptor binding. We have recently shown the existence of two distinct forms of botrocetin (one-chain and two-chain), and demonstrated that the two-chain species is approximately 30 times more active than the one-chain in promoting von Willebrand factor (vWF) binding to platelet glycoprotein (GP) Ib. The N-terminal sequence of two-chain botrocetin is highly homologous to sea-urchin Echinoidin and other Ca(2+)-dependent lectins (Fujimura et al., Biochemistry 1991; 30: 1957-64). Present data indicate that purified two-chain botrocetin binds to vWF from plasmas of patients with type IIA or IIB von Willebrand disease and its interaction is indistinguishable from that with vWF from normal individuals. However, an \"activated complex\" formed between botrocetin and IIB vWF expresses an enhanced biological activity for binding to GP Ib whereas the complex with IIA vWF has a decreased binding activity. Among several anti-vWF monoclonal antibodies (MoAbs) which inhibit ristocetin-induced platelet aggregation and/or vWF binding to GP Ib, only two MoAbs (NMC-4 and RFF-VIII RAG:1) abolished direct binding between purified botrocetin and vWF. This suggests that they recognize an epitope(s) on the vWF molecule in close proximity to the botrocetin binding site."} {"id": "PMID:1280376", "title": "Enzyme-linked immunoassays for CRM positive hemophilia A using monoclonal antibodies with defined epitopes.", "content": "Sensitive, monoclonal antibody-based, enzyme-linked immunosorbent assays (ELISAs) for plasma factor VIII (FVIII) antigen have been developed. The assays used five monoclonal anti-FVIII antibodies with known epitopes in four different pairwise combinations. The sensitivity of the assays was increased by use of the ELISA amplification method described by Bobrow et. al. (J. Immunol Methods 125:279, 1989). These assays can distinguish between CRM positive, CRM reduced and CRM negative hemophilia A. A total of 94 plasma samples from 78 different patients were screened and generally consistent results were obtained among the different assays. Such assays are potentially useful in the phenotypic and genotypic analysis of hemophilia A.", "contents": "Enzyme-linked immunoassays for CRM positive hemophilia A using monoclonal antibodies with defined epitopes. Sensitive, monoclonal antibody-based, enzyme-linked immunosorbent assays (ELISAs) for plasma factor VIII (FVIII) antigen have been developed. The assays used five monoclonal anti-FVIII antibodies with known epitopes in four different pairwise combinations. The sensitivity of the assays was increased by use of the ELISA amplification method described by Bobrow et. al. (J. Immunol Methods 125:279, 1989). These assays can distinguish between CRM positive, CRM reduced and CRM negative hemophilia A. A total of 94 plasma samples from 78 different patients were screened and generally consistent results were obtained among the different assays. Such assays are potentially useful in the phenotypic and genotypic analysis of hemophilia A."} {"id": "PMID:1280377", "title": "Tissue-type plasminogen activator, type 1 plasminogen activator inhibitor and their complex in plasma with disseminated intravascular coagulation.", "content": "The levels of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and t-PA/PAI-1 complex antigens were analyzed in the plasma of disseminated intravascular coagulation (DIC) patients and healthy controls. Other fibrinolytic parameters such as the levels of plasminogen, alpha 2-antiplasmin (alpha 2-AP), plasmin/alpha 2-AP (PAP), and D-dimer were also estimated to clarify the fibrinolytic states in these plasmas. The antigens of t-PA, PAI-1, and t-PA/PAI-1 complex were found to increase from 8.5 +/- 4.3, 54.4 +/- 21.2, and 8.6 +/- 3.5 ng/ml in normal plasma to 36.4 +/- 25.1, 106.8 +/- 54.7, and 46.6 +/- 34.5 ng/ml in DIC plasma, respectively. The molar ratio of total t-PA to total PAI-1 was 1:6 and 1:3 in normal plasma and DIC plasma, respectively, indicating an enhanced fibrinolytic state in the DIC plasma. The DIC plasma revealed a significant consumption of plasminogen (62.1 +/- 27.8%), and alpha 2-AP (63.7 +/- 25.3%) and an increase in PAP (2.6 +/- 2.7 micrograms/ml) and D-dimer (3.9 +/- 10.7 micrograms/ml). These results suggest that the production and secretion of t-PA and PAI-1 from endothelial cells were enhanced in DIC, resulting in an increased t-PA/PAI-1 complex with dominant fibrinolytic activity.", "contents": "Tissue-type plasminogen activator, type 1 plasminogen activator inhibitor and their complex in plasma with disseminated intravascular coagulation. The levels of tissue-type plasminogen activator (t-PA), type 1 plasminogen activator inhibitor (PAI-1), and t-PA/PAI-1 complex antigens were analyzed in the plasma of disseminated intravascular coagulation (DIC) patients and healthy controls. Other fibrinolytic parameters such as the levels of plasminogen, alpha 2-antiplasmin (alpha 2-AP), plasmin/alpha 2-AP (PAP), and D-dimer were also estimated to clarify the fibrinolytic states in these plasmas. The antigens of t-PA, PAI-1, and t-PA/PAI-1 complex were found to increase from 8.5 +/- 4.3, 54.4 +/- 21.2, and 8.6 +/- 3.5 ng/ml in normal plasma to 36.4 +/- 25.1, 106.8 +/- 54.7, and 46.6 +/- 34.5 ng/ml in DIC plasma, respectively. The molar ratio of total t-PA to total PAI-1 was 1:6 and 1:3 in normal plasma and DIC plasma, respectively, indicating an enhanced fibrinolytic state in the DIC plasma. The DIC plasma revealed a significant consumption of plasminogen (62.1 +/- 27.8%), and alpha 2-AP (63.7 +/- 25.3%) and an increase in PAP (2.6 +/- 2.7 micrograms/ml) and D-dimer (3.9 +/- 10.7 micrograms/ml). These results suggest that the production and secretion of t-PA and PAI-1 from endothelial cells were enhanced in DIC, resulting in an increased t-PA/PAI-1 complex with dominant fibrinolytic activity."} {"id": "PMID:1280378", "title": "Hydroxyethyl starch 200/0.5 reduces infarct volume after embolic stroke in rats.", "content": "We evaluated isovolumic hemodilution with hydroxyethyl starch 200/0.5 in a rat model of focal cerebral ischemia. This compound avoids the unfavorable viscosity and erythrocyte aggregation abnormalities of low molecular weight dextran during administration over a period of several days. Sprague-Dawley rats, anesthetized with 0.5-1% halothane and 70% N2O, were subjected to silicon cylinder (treated and control groups) or sham (sham group) embolization of the cerebral circulation. Thirty minutes after embolization, the treated group (n = 5) was infused with 11 ml/kg of 10% hydroxyethyl starch 200/0.5, and the control (n = 5) and sham (n = 4) groups were infused with saline for 1 hour. In the treated group, 7.1 ml/kg of blood was withdrawn. After 24 hours, the animals were reanesthetized, and cerebral blood flow was determined with [14C]iodoantipyrine. Alternative brain slices were either incubated with 2,3,5-triphenyltetrazolium chloride for infarct volume determination or frozen for ischemic volume and cerebral blood flow determination using autoradiography. The hematocrit in the treated group was reduced from (mean +/- SEM) 46 +/- 1% to 35 +/- 2% at 1.5 hours (p < 0.01). Cortical blood flow was within the normal range of 115-185 ml/min/100 g, except for the ischemic cortex in the embolized groups, treated and control. The ischemic and infarct volume of the treated group was reduced by 74% (p < 0.05) and 89% (p < 0.05), respectively, from the control group. The treated and sham ischemic and infarct volumes were not statistically different. These data suggest that hydroxyethyl starch 200/0.5 could be an effective treatment for ischemic stroke when administered early, because it reduces infarct and ischemic volumes from control values to levels indistinguishable from those of the sham group.", "contents": "Hydroxyethyl starch 200/0.5 reduces infarct volume after embolic stroke in rats. We evaluated isovolumic hemodilution with hydroxyethyl starch 200/0.5 in a rat model of focal cerebral ischemia. This compound avoids the unfavorable viscosity and erythrocyte aggregation abnormalities of low molecular weight dextran during administration over a period of several days. Sprague-Dawley rats, anesthetized with 0.5-1% halothane and 70% N2O, were subjected to silicon cylinder (treated and control groups) or sham (sham group) embolization of the cerebral circulation. Thirty minutes after embolization, the treated group (n = 5) was infused with 11 ml/kg of 10% hydroxyethyl starch 200/0.5, and the control (n = 5) and sham (n = 4) groups were infused with saline for 1 hour. In the treated group, 7.1 ml/kg of blood was withdrawn. After 24 hours, the animals were reanesthetized, and cerebral blood flow was determined with [14C]iodoantipyrine. Alternative brain slices were either incubated with 2,3,5-triphenyltetrazolium chloride for infarct volume determination or frozen for ischemic volume and cerebral blood flow determination using autoradiography. The hematocrit in the treated group was reduced from (mean +/- SEM) 46 +/- 1% to 35 +/- 2% at 1.5 hours (p < 0.01). Cortical blood flow was within the normal range of 115-185 ml/min/100 g, except for the ischemic cortex in the embolized groups, treated and control. The ischemic and infarct volume of the treated group was reduced by 74% (p < 0.05) and 89% (p < 0.05), respectively, from the control group. The treated and sham ischemic and infarct volumes were not statistically different. These data suggest that hydroxyethyl starch 200/0.5 could be an effective treatment for ischemic stroke when administered early, because it reduces infarct and ischemic volumes from control values to levels indistinguishable from those of the sham group."} {"id": "PMID:1280380", "title": "Hematologic and bone marrow changes after short- and long-term administration of two recombinant bovine granulocyte colony-stimulating factors.", "content": "Colony-stimulating factors are a category of glycoproteins that are instrumental in the regulation of hematopoiesis and inflammation. This investigation documented the clinical bone marrow and peripheral blood responses to short-term and long-term administration of a recombinant bovine granulocyte colony-stimulating factor (rb-GCSF) and an analog, where the cysteine at position 17 was substituted with a serine (rb-GCSF ser17). The colony-stimulating factors produced the expected changes in the hematologic findings of the bovine subjects in the study, and there was a cell-specific response to the compounds. The sustained neutrophilia in the long-term study indicates that the bovine species can tolerate the administration of recombinant forms of bovine GCSF for extended periods of time without detectable adverse side effects. The neutrophils from the short-term study revealed no apparent fluctuation, either as enhanced or reduced capability to reduce nitro blue tetrazolium as compared to pretreatment neutrophils. The administration of both recombinant forms of GCSF produced large increases in the bone marrow myeloid:erythroid (M:E) ratio concomitantly with the neutrophilias. This is the first preliminary report documenting the bone marrow response of cattle to the native and recombinant (rb-GCSF ser17) forms of bovine GCSF.", "contents": "Hematologic and bone marrow changes after short- and long-term administration of two recombinant bovine granulocyte colony-stimulating factors. Colony-stimulating factors are a category of glycoproteins that are instrumental in the regulation of hematopoiesis and inflammation. This investigation documented the clinical bone marrow and peripheral blood responses to short-term and long-term administration of a recombinant bovine granulocyte colony-stimulating factor (rb-GCSF) and an analog, where the cysteine at position 17 was substituted with a serine (rb-GCSF ser17). The colony-stimulating factors produced the expected changes in the hematologic findings of the bovine subjects in the study, and there was a cell-specific response to the compounds. The sustained neutrophilia in the long-term study indicates that the bovine species can tolerate the administration of recombinant forms of bovine GCSF for extended periods of time without detectable adverse side effects. The neutrophils from the short-term study revealed no apparent fluctuation, either as enhanced or reduced capability to reduce nitro blue tetrazolium as compared to pretreatment neutrophils. The administration of both recombinant forms of GCSF produced large increases in the bone marrow myeloid:erythroid (M:E) ratio concomitantly with the neutrophilias. This is the first preliminary report documenting the bone marrow response of cattle to the native and recombinant (rb-GCSF ser17) forms of bovine GCSF."} {"id": "PMID:1280381", "title": "Characterization of the specificity and genetic restriction of human CD4+ cytotoxic T cell clones reactive to capsid antigen of rubella virus.", "content": "Using 11 overlapping synthetic peptides covering more than 95% of the amino acid sequence of capsid protein of rubella virus, 7 CD4+ T cell clones (R10, R11, R18, A2, A10, A11, and A12) isolated from 2 rubella seropositive donors reacted strongly to rubella capsid peptides C6 (residues 119-152), C9 (residues 205-233), or C11 (residues 255-280), respectively, in both proliferation and cytotoxicity assay. Truncated peptides C6E (residues 125-139), C9B (residues 205-216), and C11E (residues 260-272) were shown to be involved directly to the T cell determinants of C6, C9, and C11, respectively. Genetic restriction of these T cell clones was analyzed by using human cell lines with various HLA-DR phenotypes as targets and/or antigen-presenting cells in cytotoxicity assay and/or proliferation assays. The results indicated that the recognition of peptide C6 by T cell clones (R11 and R18) was associated with DRw9 molecule, while the HLA restriction element of the responses of other T cell clones (A2 and A11, A10, and A12) that reacted with peptide C9 or C11 was DR4 molecule. However, there may be a cross-recognition by the T cell clone (A12) between DR1 and DR4 subtypes.", "contents": "Characterization of the specificity and genetic restriction of human CD4+ cytotoxic T cell clones reactive to capsid antigen of rubella virus. Using 11 overlapping synthetic peptides covering more than 95% of the amino acid sequence of capsid protein of rubella virus, 7 CD4+ T cell clones (R10, R11, R18, A2, A10, A11, and A12) isolated from 2 rubella seropositive donors reacted strongly to rubella capsid peptides C6 (residues 119-152), C9 (residues 205-233), or C11 (residues 255-280), respectively, in both proliferation and cytotoxicity assay. Truncated peptides C6E (residues 125-139), C9B (residues 205-216), and C11E (residues 260-272) were shown to be involved directly to the T cell determinants of C6, C9, and C11, respectively. Genetic restriction of these T cell clones was analyzed by using human cell lines with various HLA-DR phenotypes as targets and/or antigen-presenting cells in cytotoxicity assay and/or proliferation assays. The results indicated that the recognition of peptide C6 by T cell clones (R11 and R18) was associated with DRw9 molecule, while the HLA restriction element of the responses of other T cell clones (A2 and A11, A10, and A12) that reacted with peptide C9 or C11 was DR4 molecule. However, there may be a cross-recognition by the T cell clone (A12) between DR1 and DR4 subtypes."} {"id": "PMID:1280379", "title": "[Immunochemical analysis of the synthetic peptides incorporated into the protein antigenic determinant of the potato virus X coat].", "content": "Three peptides located in the N-terminal region of the potato virus X coat protein were synthesized by hand solid phase method for epitope mapping of this protein. One of these peptides (nanopeptide) interacted with monoclonal antibodies to native virus X. On the basis of these studies it was assumed, that amino acid sequence of the potato virus X coat protein, which included lysine residue in position 19, is located on the virion surface.", "contents": "[Immunochemical analysis of the synthetic peptides incorporated into the protein antigenic determinant of the potato virus X coat]. Three peptides located in the N-terminal region of the potato virus X coat protein were synthesized by hand solid phase method for epitope mapping of this protein. One of these peptides (nanopeptide) interacted with monoclonal antibodies to native virus X. On the basis of these studies it was assumed, that amino acid sequence of the potato virus X coat protein, which included lysine residue in position 19, is located on the virion surface."} {"id": "PMID:1280382", "title": "Synergistic interaction between ligands binding to the CD4 binding site and V3 domain of human immunodeficiency virus type I gp120.", "content": "We demonstrate that soluble CD4 (sCD4) or a monoclonal antibody (mAb), 39.13g, binding to a conformational epitope of gp120 involved in CD4 binding, and mAbs binding to the V3 domain of gp120, can synergistically neutralize human immunodeficiency virus type I (HIV-1). In contrast, a neutralizing mAb binding to a linear epitope within the CD4 binding domain was unable to exert a synergistic effect in combination with V3 mAbs, suggesting that synergism is dependent on ligands binding to the critical, discontinuous, gp120 residues constituting the CD4 binding site. A number of V3 mAbs showed increased binding to virion gp120 in the presence of sCD4, suggesting a mechanism for the synergistic neutralization. This effect was not observed with recombinant or detergent solubilized viral gp120, suggesting that the oligomeric structure of gp120 on viral particles affects V3 epitope exposure. This hypothesis is supported by the ability of two new V3 mAbs, 8/38c and 8/64b, to only neutralize HIV-1 in the presence of sCD4 or mAb 39.13g; binding studies demonstrate that these mAbs only bind to virion gp120 in the presence of sCD4. Thus, V3 epitope exposure is modulated by the interaction of virion gp120 with ligands specific for the CD4 binding domain and results in enhanced antibody-mediated neutralization.", "contents": "Synergistic interaction between ligands binding to the CD4 binding site and V3 domain of human immunodeficiency virus type I gp120. We demonstrate that soluble CD4 (sCD4) or a monoclonal antibody (mAb), 39.13g, binding to a conformational epitope of gp120 involved in CD4 binding, and mAbs binding to the V3 domain of gp120, can synergistically neutralize human immunodeficiency virus type I (HIV-1). In contrast, a neutralizing mAb binding to a linear epitope within the CD4 binding domain was unable to exert a synergistic effect in combination with V3 mAbs, suggesting that synergism is dependent on ligands binding to the critical, discontinuous, gp120 residues constituting the CD4 binding site. A number of V3 mAbs showed increased binding to virion gp120 in the presence of sCD4, suggesting a mechanism for the synergistic neutralization. This effect was not observed with recombinant or detergent solubilized viral gp120, suggesting that the oligomeric structure of gp120 on viral particles affects V3 epitope exposure. This hypothesis is supported by the ability of two new V3 mAbs, 8/38c and 8/64b, to only neutralize HIV-1 in the presence of sCD4 or mAb 39.13g; binding studies demonstrate that these mAbs only bind to virion gp120 in the presence of sCD4. Thus, V3 epitope exposure is modulated by the interaction of virion gp120 with ligands specific for the CD4 binding domain and results in enhanced antibody-mediated neutralization."} {"id": "PMID:1280383", "title": "5' end-dependent translation initiation of hepatitis C viral RNA and the presence of putative positive and negative translational control elements within the 5' untranslated region.", "content": "Hepatitis C virus (HCV) is a distant relative of pestiviruses and flaviviruses, but it has a 5' untranslated region (UTR) with some features structurally similar to that of picornaviruses. In order to test the role of the 5' UTR in controlling the expression of the HCV polyprotein, we fused full-length or deleted versions of the 5' UTR of HCV-1 RNA to chloramphenicol acetyl transferase (CAT) mRNA to monitor CAT activity in vivo. We found: (1) the full-length 5' UTR of HCV-1 RNA is translationally inactive while 5' deletions which mimic a 5' subgenomic RNA detected in vivo are active, (2) an efficient cis-acting element which represses translation is found at the 5' terminus, (3) a putative element which enhances translation is found near the 3' terminus of the 5' UTR, (4) additional cis-acting elements including small open reading frames (ORFs) upstream from the putative enhancer element downregulate translation. We did not find evidence supporting the existence of an internal ribosome entry site in the 5' UTR of HCV-1 RNA. These data suggest that HCV may employ a distinctive translation control strategy such as the generation of subgenomic viral mRNA in infected cells. Translational control of HCV might be responsible for some of the characteristic pathobiology seen in viral infection.", "contents": "5' end-dependent translation initiation of hepatitis C viral RNA and the presence of putative positive and negative translational control elements within the 5' untranslated region. Hepatitis C virus (HCV) is a distant relative of pestiviruses and flaviviruses, but it has a 5' untranslated region (UTR) with some features structurally similar to that of picornaviruses. In order to test the role of the 5' UTR in controlling the expression of the HCV polyprotein, we fused full-length or deleted versions of the 5' UTR of HCV-1 RNA to chloramphenicol acetyl transferase (CAT) mRNA to monitor CAT activity in vivo. We found: (1) the full-length 5' UTR of HCV-1 RNA is translationally inactive while 5' deletions which mimic a 5' subgenomic RNA detected in vivo are active, (2) an efficient cis-acting element which represses translation is found at the 5' terminus, (3) a putative element which enhances translation is found near the 3' terminus of the 5' UTR, (4) additional cis-acting elements including small open reading frames (ORFs) upstream from the putative enhancer element downregulate translation. We did not find evidence supporting the existence of an internal ribosome entry site in the 5' UTR of HCV-1 RNA. These data suggest that HCV may employ a distinctive translation control strategy such as the generation of subgenomic viral mRNA in infected cells. Translational control of HCV might be responsible for some of the characteristic pathobiology seen in viral infection."} {"id": "PMID:1280384", "title": "The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein.", "content": "To study the role of the precursor to the membrane protein (prM) in flavivirus maturation, we inhibited the proteolytic processing of the Murray Valley encephalitis (MVE) virus prM to membrane protein in infected cells by adding the acidotropic agent ammonium chloride late in the virus replication cycle. Viruses purified from supernatants of ammonium chloride-treated cells contained prM protein and were unable to fuse C6/36 mosquito cells from without. When ammonium chloride was removed from the cells, both the processing of prM and the fusion activity of the purified viruses were partially restored. By using monoclonal antibodies (MAbs) specific for the envelope (E) glycoprotein of MVE virus, we found that at least three epitopes were less accessible to their corresponding antibodies in the prM-containing MVE virus particles. Amino-terminal sequencing of proteolytic fragments of the E protein which were reactive with sequence-specific peptide antisera or MAb enabled us to estimate the site of the E protein interacting with the prM to be within amino acids 200 to 327. Since prM-containing viruses were up to 400-fold more resistant to a low pH environment, we conclude that the E-prM interaction might be necessary to protect the E protein from irreversible conformational changes caused by maturation into the acidic vesicles of the exocytic pathway.", "contents": "The Murray Valley encephalitis virus prM protein confers acid resistance to virus particles and alters the expression of epitopes within the R2 domain of E glycoprotein. To study the role of the precursor to the membrane protein (prM) in flavivirus maturation, we inhibited the proteolytic processing of the Murray Valley encephalitis (MVE) virus prM to membrane protein in infected cells by adding the acidotropic agent ammonium chloride late in the virus replication cycle. Viruses purified from supernatants of ammonium chloride-treated cells contained prM protein and were unable to fuse C6/36 mosquito cells from without. When ammonium chloride was removed from the cells, both the processing of prM and the fusion activity of the purified viruses were partially restored. By using monoclonal antibodies (MAbs) specific for the envelope (E) glycoprotein of MVE virus, we found that at least three epitopes were less accessible to their corresponding antibodies in the prM-containing MVE virus particles. Amino-terminal sequencing of proteolytic fragments of the E protein which were reactive with sequence-specific peptide antisera or MAb enabled us to estimate the site of the E protein interacting with the prM to be within amino acids 200 to 327. Since prM-containing viruses were up to 400-fold more resistant to a low pH environment, we conclude that the E-prM interaction might be necessary to protect the E protein from irreversible conformational changes caused by maturation into the acidic vesicles of the exocytic pathway."} {"id": "PMID:1280385", "title": "CD4-independent inhibition of lymphocyte proliferation mediated by HIV-1 envelope glycoproteins.", "content": "The cytopathic effects of HIV-1 produced by direct infection of human T cells do not account for the disproportionate loss of CD4-positive lymphocytes during the course of HIV infection. Previous studies have demonstrated the inhibition of uninfected human T cell activation and proliferation by the HIV-1 envelope glycoproteins, presumably due to gp120-CD4 interactions. To examine the ability of HIV-1 to inhibit T cell proliferation in the absence of both direct infection and gp120-CD4 interactions, we tested the effect of HIV-1 on mouse T cell proliferation. Culture media containing HIV-1 released from infected cells inhibited T lymphocyte proliferation in response to interleukin-2 (IL-2). Studies to explore the mechanism of this inhibition suggested that the decrease in proliferation resulted from interactions between HIV-1 and the mouse cells, but did not involve IL-2/IL-2 receptor interactions. We used monoclonal antibodies to demonstrate that the HIV-1 envelope glycoproteins were required for the inhibition of murine T cell proliferation. Anti-gp120 antibodies completely restored proliferation, indicating that the surface protein gp120 was primarily required for the inhibition of proliferation. However, antibodies directed against the transmembrane protein of HIV-1 (gp41) also partially restored lymphocyte proliferation. The functional significance of the HIV-1 envelope protein epitopes recognized by the monoclonal antibodies is discussed.", "contents": "CD4-independent inhibition of lymphocyte proliferation mediated by HIV-1 envelope glycoproteins. The cytopathic effects of HIV-1 produced by direct infection of human T cells do not account for the disproportionate loss of CD4-positive lymphocytes during the course of HIV infection. Previous studies have demonstrated the inhibition of uninfected human T cell activation and proliferation by the HIV-1 envelope glycoproteins, presumably due to gp120-CD4 interactions. To examine the ability of HIV-1 to inhibit T cell proliferation in the absence of both direct infection and gp120-CD4 interactions, we tested the effect of HIV-1 on mouse T cell proliferation. Culture media containing HIV-1 released from infected cells inhibited T lymphocyte proliferation in response to interleukin-2 (IL-2). Studies to explore the mechanism of this inhibition suggested that the decrease in proliferation resulted from interactions between HIV-1 and the mouse cells, but did not involve IL-2/IL-2 receptor interactions. We used monoclonal antibodies to demonstrate that the HIV-1 envelope glycoproteins were required for the inhibition of murine T cell proliferation. Anti-gp120 antibodies completely restored proliferation, indicating that the surface protein gp120 was primarily required for the inhibition of proliferation. However, antibodies directed against the transmembrane protein of HIV-1 (gp41) also partially restored lymphocyte proliferation. The functional significance of the HIV-1 envelope protein epitopes recognized by the monoclonal antibodies is discussed."} {"id": "PMID:1280386", "title": "Identification of amino acids located in the antibody binding sites of human hepatitis A virus.", "content": "Antigenic mutants of human hepatitis A virus (human-HAV) were isolated by their resistance to neutralizing monoclonal antibodies raised to human-HAV. The nucleotide sequence determined for the capsid regions of 12 mutants identified amino acid changes that clustered in three non-overlapping sites; one in VP3 and two in VP1. All mutants had a change at amino acid residue 70 in VP3, indicating its primary importance for antibody binding. Ten mutants had two amino acid changes occurring in the VP3 site as well as one in one of the two VP1 sites. These data suggest that both sites in VP1 interact with the single VP3 site to form the immunodominant epitope of HAV. The amino acid changes found in the antigenic mutants of human-HAV selected in this study were located in the same positions as changes found in strains of HAV isolated from Old World monkeys. These simian strains of HAV are not recognized by most monoclonal antibodies raised to human-HAV, suggesting that the observed amino acid changes are part of the antibody binding site.", "contents": "Identification of amino acids located in the antibody binding sites of human hepatitis A virus. Antigenic mutants of human hepatitis A virus (human-HAV) were isolated by their resistance to neutralizing monoclonal antibodies raised to human-HAV. The nucleotide sequence determined for the capsid regions of 12 mutants identified amino acid changes that clustered in three non-overlapping sites; one in VP3 and two in VP1. All mutants had a change at amino acid residue 70 in VP3, indicating its primary importance for antibody binding. Ten mutants had two amino acid changes occurring in the VP3 site as well as one in one of the two VP1 sites. These data suggest that both sites in VP1 interact with the single VP3 site to form the immunodominant epitope of HAV. The amino acid changes found in the antigenic mutants of human-HAV selected in this study were located in the same positions as changes found in strains of HAV isolated from Old World monkeys. These simian strains of HAV are not recognized by most monoclonal antibodies raised to human-HAV, suggesting that the observed amino acid changes are part of the antibody binding site."} {"id": "PMID:1280387", "title": "[A histochemical analysis of the reactions of the lymphoid organs and liver in a radiation lesion (experimental research)].", "content": "A histochemical study is presented of the functional state of the lymphoid organs and liver of guinea pigs under the effect of small and large doses of roentgen rays. Changes were found in the quantitative content of nucleic acids and lipofuscin already several days after irradiation accompanied by structural-qualitative reorganization of cells.", "contents": "[A histochemical analysis of the reactions of the lymphoid organs and liver in a radiation lesion (experimental research)]. A histochemical study is presented of the functional state of the lymphoid organs and liver of guinea pigs under the effect of small and large doses of roentgen rays. Changes were found in the quantitative content of nucleic acids and lipofuscin already several days after irradiation accompanied by structural-qualitative reorganization of cells."} {"id": "PMID:1280388", "title": "[The factors influencing the incidence of heart rhythm disorders after the radical correction of the tetralogy of Fallot].", "content": "The frequency and factors favouring the development of cardiac rhythm disorders were studied in 306 patients operated on radically for Fallot's tetralogy (follow-up: 6 months--29 years). This complication was found in 99 patients (32.3%). Most patients showed ventricular arrhythmia--62 (62.6%). Paroxysmal tachycardia was noted in 11 patients, atrio-ventricular block in 15 patients, combination of different arrhythmias in 11 patients. Risk factors were: inadequate correction of the malformation, age over 15 at the time of operation, approach through the right ventricle with plastic repair of the drainage tract, five years after surgery.", "contents": "[The factors influencing the incidence of heart rhythm disorders after the radical correction of the tetralogy of Fallot]. The frequency and factors favouring the development of cardiac rhythm disorders were studied in 306 patients operated on radically for Fallot's tetralogy (follow-up: 6 months--29 years). This complication was found in 99 patients (32.3%). Most patients showed ventricular arrhythmia--62 (62.6%). Paroxysmal tachycardia was noted in 11 patients, atrio-ventricular block in 15 patients, combination of different arrhythmias in 11 patients. Risk factors were: inadequate correction of the malformation, age over 15 at the time of operation, approach through the right ventricle with plastic repair of the drainage tract, five years after surgery."} {"id": "PMID:1280390", "title": "Plasma levels of insulin-like growth factor binding protein-1, and growth hormone binding protein activity from birth to the third month of life.", "content": "Serum levels of insulin-like growth factors (IGF-1 and IGF-2), insulin, insulin-like growth factor binding protein-1 (IGFBP-1), growth hormone (GH) and growth hormone-binding protein (GH-BP) activity were assessed in a group of healthy newborns and reevaluated at one and three months of life in six of them. A significant decrease in IGFBP-1 plasma levels was observed at one month (p < 0.002) and three months (p < 0.02) of life compared to cord blood values. IGF-1 plasma levels did not change during the first three months of life. In contrast, IGF-2 plasma levels increased significantly at three months of life compared to cord blood values (p < 0.002). GH plasma levels showed a significant decrease at three months of life (p < 0.03). GH-BP activity was low at birth and did not change significantly during the first three months of life. The low GH-BP activity may reflect the GH receptor status, indicating that GH receptors are poorly expressed in early infancy. The high IGFBP-1 plasma levels in newborns could be important in protecting them from hypoglycemia.", "contents": "Plasma levels of insulin-like growth factor binding protein-1, and growth hormone binding protein activity from birth to the third month of life. Serum levels of insulin-like growth factors (IGF-1 and IGF-2), insulin, insulin-like growth factor binding protein-1 (IGFBP-1), growth hormone (GH) and growth hormone-binding protein (GH-BP) activity were assessed in a group of healthy newborns and reevaluated at one and three months of life in six of them. A significant decrease in IGFBP-1 plasma levels was observed at one month (p < 0.002) and three months (p < 0.02) of life compared to cord blood values. IGF-1 plasma levels did not change during the first three months of life. In contrast, IGF-2 plasma levels increased significantly at three months of life compared to cord blood values (p < 0.002). GH plasma levels showed a significant decrease at three months of life (p < 0.03). GH-BP activity was low at birth and did not change significantly during the first three months of life. The low GH-BP activity may reflect the GH receptor status, indicating that GH receptors are poorly expressed in early infancy. The high IGFBP-1 plasma levels in newborns could be important in protecting them from hypoglycemia."} {"id": "PMID:1280389", "title": "Phenotypic analysis of bronchoalveolar lavage lymphocytes from acquired immunodeficiency patients with and without Pneumocystis carinii pneumonia.", "content": "A study was performed to reveal possible differences in lymphocyte subpopulations from bronchoalveolar lavage (BAL) of acquired immunodeficiency patients with and without Pneumocystis carinii pneumonia. Forty-one consecutive human immunodeficiency virus-seropositive patients were studied. Pneumocystis carinii infection was detected in the BAL fluid from 18 patients. The BAL lymphocyte subpopulations were determined by surface marker analysis with the immunoperoxidase slide assay. No significant differences in the percentage of CD4+ and CD8+ lymphocytes were found between the two groups. The percentage of CD57+ natural killer (NK) cells was significantly higher in the Pneumocystis carinii-negative group than in the -positive group. Since NK cells protect from microbial infections, it is conceivable that the loss of CD57+ NK cells may be one of the phenomena leading to the immunodeficiency state that underlies the pulmonary complications characteristic of the acquired immunodeficiency syndrome.", "contents": "Phenotypic analysis of bronchoalveolar lavage lymphocytes from acquired immunodeficiency patients with and without Pneumocystis carinii pneumonia. A study was performed to reveal possible differences in lymphocyte subpopulations from bronchoalveolar lavage (BAL) of acquired immunodeficiency patients with and without Pneumocystis carinii pneumonia. Forty-one consecutive human immunodeficiency virus-seropositive patients were studied. Pneumocystis carinii infection was detected in the BAL fluid from 18 patients. The BAL lymphocyte subpopulations were determined by surface marker analysis with the immunoperoxidase slide assay. No significant differences in the percentage of CD4+ and CD8+ lymphocytes were found between the two groups. The percentage of CD57+ natural killer (NK) cells was significantly higher in the Pneumocystis carinii-negative group than in the -positive group. Since NK cells protect from microbial infections, it is conceivable that the loss of CD57+ NK cells may be one of the phenomena leading to the immunodeficiency state that underlies the pulmonary complications characteristic of the acquired immunodeficiency syndrome."} {"id": "PMID:1280391", "title": "Serum parathyroid hormone-related protein concentrations in patients with hematologic malignancies or solid tumors.", "content": "The clinical significance of parathyroid hormone-related protein in humoral hypercalcemia of malignancy was investigated by determining the serum parathyroid hormone-related protein concentrations in 167 normal subjects, 56 patients with hematologic malignancy and 144 patients with solid tumor. Serum parathyroid hormone-related protein was measured with a radioimmunoassay kit that recognizes the C-terminal portion of the molecule. The serum parathyroid hormone-related protein concentrations were 20.2-50.8 pmol/l (mean +/- 2 SD) in normal subjects, and were elevated in 80% of the patients with malignancies with hypercalcemia, including squamous cell carcinoma and adult T cell leukemia. Moreover, two cases of B cell non-Hodgkin's lymphoma with hypercalcemia had high serum parathyroid hormone-related protein concentrations, which varied in parallel with the tumor size during the clinical course. Of 136 patients with solid tumors with normocalcemia, the serum parathyroid hormone-related protein concentration was slightly elevated in only 5.1%, all of whom were at an advanced stage. These data indicate that determination of the serum parathyroid hormone-related protein concentration is useful for differential diagnosis of humoral hypercalcemia of malignancy and prediction of its development.", "contents": "Serum parathyroid hormone-related protein concentrations in patients with hematologic malignancies or solid tumors. The clinical significance of parathyroid hormone-related protein in humoral hypercalcemia of malignancy was investigated by determining the serum parathyroid hormone-related protein concentrations in 167 normal subjects, 56 patients with hematologic malignancy and 144 patients with solid tumor. Serum parathyroid hormone-related protein was measured with a radioimmunoassay kit that recognizes the C-terminal portion of the molecule. The serum parathyroid hormone-related protein concentrations were 20.2-50.8 pmol/l (mean +/- 2 SD) in normal subjects, and were elevated in 80% of the patients with malignancies with hypercalcemia, including squamous cell carcinoma and adult T cell leukemia. Moreover, two cases of B cell non-Hodgkin's lymphoma with hypercalcemia had high serum parathyroid hormone-related protein concentrations, which varied in parallel with the tumor size during the clinical course. Of 136 patients with solid tumors with normocalcemia, the serum parathyroid hormone-related protein concentration was slightly elevated in only 5.1%, all of whom were at an advanced stage. These data indicate that determination of the serum parathyroid hormone-related protein concentration is useful for differential diagnosis of humoral hypercalcemia of malignancy and prediction of its development."} {"id": "PMID:1280392", "title": "Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature.", "content": "Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p < 0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N = 10) or subcutaneous (N = 9) administration of IGF-I (75 micrograms.kg-1 and 150 micrograms.kg-1, respectively) in LTD children resulted in a rapid 50-60% fall in serum insulin (p < 0.02), a decline in blood glucose and a concomitant 40-60% rise of IGFBP-1 levels (p < 0.05). Treatment for seven days with IGF-I (150 micrograms.kg-1 x d-1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p < 0.05), in GHD adults by 52% (p < 0.02) and in children with constitutional short stature by 17% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature. Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p < 0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N = 10) or subcutaneous (N = 9) administration of IGF-I (75 micrograms.kg-1 and 150 micrograms.kg-1, respectively) in LTD children resulted in a rapid 50-60% fall in serum insulin (p < 0.02), a decline in blood glucose and a concomitant 40-60% rise of IGFBP-1 levels (p < 0.05). Treatment for seven days with IGF-I (150 micrograms.kg-1 x d-1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p < 0.05), in GHD adults by 52% (p < 0.02) and in children with constitutional short stature by 17% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280393", "title": "Determination of insulin-like growth factor-2 in feto-maternal circulation during human pregnancy.", "content": "In order to clarify the roles of insulin-like growth factors (IGFs) on the human maternal-fetal environment, IGF-2 and IGF-1 levels were investigated in human plasma and amniotic fluid during pregnancy. Initially, new radio-immunoassay (RIA) systems for human IGF-2 could be developed. The sensitivity of this assay was 17.5 pg/tube and the cross-reactivity with IGF-1 was 0.64%. The pattern of change of maternal plasma IGF-2 in early pregnancy differed from that of IGF-1, but both IGF levels increased progressively in the second half of gestation, and decreased to non-pregnancy levels in the puerperium. Maternal levels of IGF-2 were approximately seven times greater than those of IGF-1. The ratio of IGF-2 to IGF-1 was 3.2 in amniotic fluid. The IGF concentrations in amniotic fluid obtained in the second trimester were significantly greater than those of term specimens, and closely related to those of prolactin (PRL) in amniotic fluid. The highest IGF-2 to IGF-1 ratio (15.9) was found in umbilical vein plasma. On Sephadex G-150 gel-chromatography of maternal and fetal plasma at term, two apparent peaks of unsaturated IGF-2 binding protein (BP) could be detected in both 150 and 40 kilo dalton (kD) regions. One main peak of unsaturated IGF-2 BP could be determined in the 40 kD region in the amniotic fluid at term. High concentration of IGF-2 could be detected in feto-maternal circulation during human pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Determination of insulin-like growth factor-2 in feto-maternal circulation during human pregnancy. In order to clarify the roles of insulin-like growth factors (IGFs) on the human maternal-fetal environment, IGF-2 and IGF-1 levels were investigated in human plasma and amniotic fluid during pregnancy. Initially, new radio-immunoassay (RIA) systems for human IGF-2 could be developed. The sensitivity of this assay was 17.5 pg/tube and the cross-reactivity with IGF-1 was 0.64%. The pattern of change of maternal plasma IGF-2 in early pregnancy differed from that of IGF-1, but both IGF levels increased progressively in the second half of gestation, and decreased to non-pregnancy levels in the puerperium. Maternal levels of IGF-2 were approximately seven times greater than those of IGF-1. The ratio of IGF-2 to IGF-1 was 3.2 in amniotic fluid. The IGF concentrations in amniotic fluid obtained in the second trimester were significantly greater than those of term specimens, and closely related to those of prolactin (PRL) in amniotic fluid. The highest IGF-2 to IGF-1 ratio (15.9) was found in umbilical vein plasma. On Sephadex G-150 gel-chromatography of maternal and fetal plasma at term, two apparent peaks of unsaturated IGF-2 binding protein (BP) could be detected in both 150 and 40 kilo dalton (kD) regions. One main peak of unsaturated IGF-2 BP could be determined in the 40 kD region in the amniotic fluid at term. High concentration of IGF-2 could be detected in feto-maternal circulation during human pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280394", "title": "High dose aprotinin to reduce blood loss in patients undergoing redo open heart surgery.", "content": "Recently, aprotinin has been demonstrated to be effective in reducing post-operative bleeding after open heart surgery. The aim of this study was to evaluate the effectiveness of high dose aprotinin in patients undergoing redo open heart surgery in whom perioperative bleeding is generally increased. Fifty-eight patients, mean age 55 years, underwent a second open heart surgery for single valve replacement in 37 patients (mitral or aortic), for double valve replacement in 16 patients and for coronary artery by-pass grafting in 4 patients. In 30 of the 58 patients (Group A) aprotinin was infused with the following scheme: 2 million KIU in 30 minutes during induction of anesthesia, 2 million KIU in the priming volume of extracorporeal circulation and 500,000 KIU every hour until the end of the surgical procedure. The remaining 28 patients served as control group (Group B). No adverse reactions to aprotinin were observed. There was no significant difference in cardiopulmonary by-pass time and minimum temperature achieved between the two groups of patients. During the operative day blood loss was significantly lower in group A than in group B (492 +/- 336 ml vs. 628 +/- 273 ml) (p < 0.01). This difference was not significant during the following days. However 3 days after the operation a still significant difference was reported in total blood loss between group A and group B (816 +/- 507 ml vs. 1018 +/- 373 ml) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "High dose aprotinin to reduce blood loss in patients undergoing redo open heart surgery. Recently, aprotinin has been demonstrated to be effective in reducing post-operative bleeding after open heart surgery. The aim of this study was to evaluate the effectiveness of high dose aprotinin in patients undergoing redo open heart surgery in whom perioperative bleeding is generally increased. Fifty-eight patients, mean age 55 years, underwent a second open heart surgery for single valve replacement in 37 patients (mitral or aortic), for double valve replacement in 16 patients and for coronary artery by-pass grafting in 4 patients. In 30 of the 58 patients (Group A) aprotinin was infused with the following scheme: 2 million KIU in 30 minutes during induction of anesthesia, 2 million KIU in the priming volume of extracorporeal circulation and 500,000 KIU every hour until the end of the surgical procedure. The remaining 28 patients served as control group (Group B). No adverse reactions to aprotinin were observed. There was no significant difference in cardiopulmonary by-pass time and minimum temperature achieved between the two groups of patients. During the operative day blood loss was significantly lower in group A than in group B (492 +/- 336 ml vs. 628 +/- 273 ml) (p < 0.01). This difference was not significant during the following days. However 3 days after the operation a still significant difference was reported in total blood loss between group A and group B (816 +/- 507 ml vs. 1018 +/- 373 ml) (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280395", "title": "Blood loss and use of blood in internal mammary artery and saphenous vein bypass grafting with and without adding a single, low-dose of aprotinin (2 million units) to the pump prime.", "content": "In comparison with saphenous vein bypass grafting (SVG) without a pleurotomy, internal mammary artery (IMA) bypass surgery might enhance more blood loss by the intrathoracic wound and a wide opened pleura. Low-dose aprotinin (Trasylol) reduces blood loss and consequently, the use of homologous blood. We studied the blood loss and blood requirements peri-operatively in 70 patients, who underwent either SVG-(n = 35) or IMA-surgery (n = 35) without aprotinin and another 70 patients who underwent SVG- (n = 35) or IMA-surgery (n = 35) with a single dose of aprotinin, added to the pump prime. We also determined the hemoglobin and total protein content of the shed blood. Without aprotinin administration, the mean intra-operative and post-operative blood loss was significantly less (p < 0.01) in SVG-patients, than in IMA-patients. We observed no statistical differences in the mean blood requirements between SVG- and IMA-surgery (1.2 units and 1.6 units). The use of any homologous blood product was similarly averted in 39% of the SVG-patients, and in 48% of the IMA-patients. Treatment with aprotinin significantly lessened (p < 0.01) the mean intra-operative blood loss only in IMA-patients. Post-operative blood loss was diminished with 45% in IMA-patients and 33% in SVG-patients, being significantly less (p < 0.01) after SVG, than after IMA-surgery. Blood requirements were significantly lowered (p < 0.01): a total mean of 0.2 units in SVG- and 0.6 units in IMA-patients (NS). Any homologous blood product was prevented in 78% of the IMA-patients and in 87% of the SVG-patients (NS). The mean loss of hemoglobin and total protein per 100 ml of shed blood was similar in IMA-, and SVG-patients with or without aprotinin, although aprotinin diminished the total amounts in both groups with 50% (p < 0.01).", "contents": "Blood loss and use of blood in internal mammary artery and saphenous vein bypass grafting with and without adding a single, low-dose of aprotinin (2 million units) to the pump prime. In comparison with saphenous vein bypass grafting (SVG) without a pleurotomy, internal mammary artery (IMA) bypass surgery might enhance more blood loss by the intrathoracic wound and a wide opened pleura. Low-dose aprotinin (Trasylol) reduces blood loss and consequently, the use of homologous blood. We studied the blood loss and blood requirements peri-operatively in 70 patients, who underwent either SVG-(n = 35) or IMA-surgery (n = 35) without aprotinin and another 70 patients who underwent SVG- (n = 35) or IMA-surgery (n = 35) with a single dose of aprotinin, added to the pump prime. We also determined the hemoglobin and total protein content of the shed blood. Without aprotinin administration, the mean intra-operative and post-operative blood loss was significantly less (p < 0.01) in SVG-patients, than in IMA-patients. We observed no statistical differences in the mean blood requirements between SVG- and IMA-surgery (1.2 units and 1.6 units). The use of any homologous blood product was similarly averted in 39% of the SVG-patients, and in 48% of the IMA-patients. Treatment with aprotinin significantly lessened (p < 0.01) the mean intra-operative blood loss only in IMA-patients. Post-operative blood loss was diminished with 45% in IMA-patients and 33% in SVG-patients, being significantly less (p < 0.01) after SVG, than after IMA-surgery. Blood requirements were significantly lowered (p < 0.01): a total mean of 0.2 units in SVG- and 0.6 units in IMA-patients (NS). Any homologous blood product was prevented in 78% of the IMA-patients and in 87% of the SVG-patients (NS). The mean loss of hemoglobin and total protein per 100 ml of shed blood was similar in IMA-, and SVG-patients with or without aprotinin, although aprotinin diminished the total amounts in both groups with 50% (p < 0.01)."} {"id": "PMID:1280396", "title": "Proliferative activity in normal salivary gland and pleomorphic adenoma. A study by argyrophilic nucleolar organizer region (AgNOR) staining.", "content": "Proliferative activity of the structural components of normal salivary glands (27 cases) and characteristic histological areas in salivary pleomorphic adenoma (51 cases) was examined by visualization of argyrophilic nucleolar organizer regions (AgNORs). In the normal salivary gland, there were clusters of cells, each with two or three AgNOR dots, within the intercalated ducts. The mean number of AgNORs in this portion was 1.80, which was significantly higher than in the other epithelial parts. This indicates vigorous proliferative activity of the intercalated ducts, and thus the ducts may play an important role as reserve cells in neoplastic transformation. In pleomorphic adenoma, solid nests had a high AgNOR count (1.61), showing a significant difference from the tumor cells scattered in the \"stroma\". Thus the decrease in proliferative ability might occur concurrently with formation of the extracellular matrix.", "contents": "Proliferative activity in normal salivary gland and pleomorphic adenoma. A study by argyrophilic nucleolar organizer region (AgNOR) staining. Proliferative activity of the structural components of normal salivary glands (27 cases) and characteristic histological areas in salivary pleomorphic adenoma (51 cases) was examined by visualization of argyrophilic nucleolar organizer regions (AgNORs). In the normal salivary gland, there were clusters of cells, each with two or three AgNOR dots, within the intercalated ducts. The mean number of AgNORs in this portion was 1.80, which was significantly higher than in the other epithelial parts. This indicates vigorous proliferative activity of the intercalated ducts, and thus the ducts may play an important role as reserve cells in neoplastic transformation. In pleomorphic adenoma, solid nests had a high AgNOR count (1.61), showing a significant difference from the tumor cells scattered in the \"stroma\". Thus the decrease in proliferative ability might occur concurrently with formation of the extracellular matrix."} {"id": "PMID:1280397", "title": "Lipid-protein interactions in neurotropic Na-pump regulation.", "content": "The role of lipid-protein interaction in the regulation of the brain Na-pump by different neurotropic agents (prostaglandin E2, middle molecules from blood plasma of uremic patients, neuropeptide galanin, the oligopeptide fraction from brain) was investigated. We established a definite correlation between the lipid status (the peroxidativity of the lipids, the phospholipids and cholesterol content) of the Na,K-ATPase enzyme preparation (plasma membrane fragments) and the influence of the neurotropic agents. Besides, after the treatment with delipidative agents (phospholipase A2, SDS) the inhibitory effects of these neurotropic agents, were diminished significantly. These facts do not contradict our previous suggestion that the lipid-protein interactions underlay the regulative action mechanism of the natural bioactive ligands.", "contents": "Lipid-protein interactions in neurotropic Na-pump regulation. The role of lipid-protein interaction in the regulation of the brain Na-pump by different neurotropic agents (prostaglandin E2, middle molecules from blood plasma of uremic patients, neuropeptide galanin, the oligopeptide fraction from brain) was investigated. We established a definite correlation between the lipid status (the peroxidativity of the lipids, the phospholipids and cholesterol content) of the Na,K-ATPase enzyme preparation (plasma membrane fragments) and the influence of the neurotropic agents. Besides, after the treatment with delipidative agents (phospholipase A2, SDS) the inhibitory effects of these neurotropic agents, were diminished significantly. These facts do not contradict our previous suggestion that the lipid-protein interactions underlay the regulative action mechanism of the natural bioactive ligands."} {"id": "PMID:1280398", "title": "Expression of insulin-like growth factors (IGFs) and their binding proteins (IGF BPs) during pancreatic development in rat, and modulation of IGF actions on rat islet DNA synthesis by IGF BPs.", "content": "Growth of pancreatic beta-cells is an essential feature of development in order to maintain insulin availability. While glucose has been shown to increase beta-cell DNA synthetic rate in cultures of isolated islets of Langerhans, there is also evidence for a local control of beta-cell growth involving insulin-like growth factors (IGFs). IGF I and II and their specific binding proteins (IGF BPs) are expressed within the developing rat pancreas, and released by isolated fetal rat islets of Langerhans. Glucose-induced beta-cell growth is not mediated by IGF-I, since IGF release does not alter in response to changes in glucose availability. In contrast, IGF BP release is positively associated with glucose concentrations over the physiological range and is therefore a candidate. Exogenous hIGF BP1 or bIGF BP2 synergistically interacted with hIGF I or II to increase DNA synthesis within isolated fetal rat islets. These results suggest a role for IGF BPs in the regulation of beta-cell growth. They may act independently or by modulation of IGF bioavailability during pancreatic development.", "contents": "Expression of insulin-like growth factors (IGFs) and their binding proteins (IGF BPs) during pancreatic development in rat, and modulation of IGF actions on rat islet DNA synthesis by IGF BPs. Growth of pancreatic beta-cells is an essential feature of development in order to maintain insulin availability. While glucose has been shown to increase beta-cell DNA synthetic rate in cultures of isolated islets of Langerhans, there is also evidence for a local control of beta-cell growth involving insulin-like growth factors (IGFs). IGF I and II and their specific binding proteins (IGF BPs) are expressed within the developing rat pancreas, and released by isolated fetal rat islets of Langerhans. Glucose-induced beta-cell growth is not mediated by IGF-I, since IGF release does not alter in response to changes in glucose availability. In contrast, IGF BP release is positively associated with glucose concentrations over the physiological range and is therefore a candidate. Exogenous hIGF BP1 or bIGF BP2 synergistically interacted with hIGF I or II to increase DNA synthesis within isolated fetal rat islets. These results suggest a role for IGF BPs in the regulation of beta-cell growth. They may act independently or by modulation of IGF bioavailability during pancreatic development."} {"id": "PMID:1280400", "title": "Growth factor expression in normal and diabetic rats during peripheral nerve regeneration through silicone tubes.", "content": "The silicone tube model of regeneration has proved to be an invaluable tool for experimental studies aimed at understanding expression of growth factors during normal and abnormal metabolic states of regeneration. Since the morphological parameters of nerve growth and myelination are well-defined and easily identified in this model, the expression of both diffusible and intracellular-acting growth factors can be readily correlated with the occurrence of these cellular events. These studies facilitate the study of the cellular and molecular events that accompany regeneration. Further, because the sciatic nerve can be traced up to its corresponding neurons, growth factor gene expression can also be studied by in situ hybridization and Northern blotting techniques. This is particularly important in defining the cell source of extracellularly released growth factors. Finally, and most importantly, the regeneration process in the normal or diseased metabolic state (such as diabetes) can be manipulated via the administration of adjuncts to the tube that either promote or inhibit regeneration. Further studies in this regard, and in the identification of growth factors involved and their role during regeneration should shed some light on the pathogenesis and possible means of mitigating or reversing diabetic neuropathy.", "contents": "Growth factor expression in normal and diabetic rats during peripheral nerve regeneration through silicone tubes. The silicone tube model of regeneration has proved to be an invaluable tool for experimental studies aimed at understanding expression of growth factors during normal and abnormal metabolic states of regeneration. Since the morphological parameters of nerve growth and myelination are well-defined and easily identified in this model, the expression of both diffusible and intracellular-acting growth factors can be readily correlated with the occurrence of these cellular events. These studies facilitate the study of the cellular and molecular events that accompany regeneration. Further, because the sciatic nerve can be traced up to its corresponding neurons, growth factor gene expression can also be studied by in situ hybridization and Northern blotting techniques. This is particularly important in defining the cell source of extracellularly released growth factors. Finally, and most importantly, the regeneration process in the normal or diseased metabolic state (such as diabetes) can be manipulated via the administration of adjuncts to the tube that either promote or inhibit regeneration. Further studies in this regard, and in the identification of growth factors involved and their role during regeneration should shed some light on the pathogenesis and possible means of mitigating or reversing diabetic neuropathy."} {"id": "PMID:1280401", "title": "Interferon--a candidate mediator of cell growth.", "content": "The IFNs are a class of compounds comprising at least three different entities alpha, beta, gamma, with a clearly defined capacity to enhance expression of MHC antigens, as well as modulate growth in a variety of tissues. They are thus candidates for autoimmune cellular destruction and growth modulation. IFN has now been shown to modulate important developmental and injury-related events in both the pancreas and CNS. Other cytokines may also be important players in these biological events and it remains to be elucidated how IFN and other cytokines exert their effects in these organs.", "contents": "Interferon--a candidate mediator of cell growth. The IFNs are a class of compounds comprising at least three different entities alpha, beta, gamma, with a clearly defined capacity to enhance expression of MHC antigens, as well as modulate growth in a variety of tissues. They are thus candidates for autoimmune cellular destruction and growth modulation. IFN has now been shown to modulate important developmental and injury-related events in both the pancreas and CNS. Other cytokines may also be important players in these biological events and it remains to be elucidated how IFN and other cytokines exert their effects in these organs."} {"id": "PMID:1280402", "title": "Response rate and cell-cycle changes due to intra-arterial infusion chemotherapy with cisplatin and bleomycin for locally recurrent uterine cervical cancer.", "content": "Intra-arterial infusion with cisplatin (CDDP) and bleomycin (BLM) was carried out in 21 patients with locally recurrent uterine cervical cancer who were previously treated with irradiation alone. Patients were treated with a bolus infusion into both internal iliac arteries of 50 mg/m2 of CDDP and 30 mg/m2 of BLM. Two to four courses of the infusion therapy were given to each patient, and the response rate, the tumor and serum drug concentrations, and the cell kinetics in tumor tissue were evaluated. The response rate (CR+PR) was 71.4% according to the WHO criteria. There was no difference, in the tumor tissue concentrations of CDDP and BLM between responders and nonresponders. Although the DNA ploidy of tumor cells was not significantly different between the two groups before treatment, both the labeling index with BrdU and the proliferation index with flow cytometry significantly increased 24 hours after treatment in responding tumors but not in nonresponding tumors. These results show that intra-arterial infusion with CDDP and BLM improves the prognosis of recurrent cervical cancer and that labeling and proliferation indices may be useful for determining the response of cervical cancer to intra-arterial chemotherapy.", "contents": "Response rate and cell-cycle changes due to intra-arterial infusion chemotherapy with cisplatin and bleomycin for locally recurrent uterine cervical cancer. Intra-arterial infusion with cisplatin (CDDP) and bleomycin (BLM) was carried out in 21 patients with locally recurrent uterine cervical cancer who were previously treated with irradiation alone. Patients were treated with a bolus infusion into both internal iliac arteries of 50 mg/m2 of CDDP and 30 mg/m2 of BLM. Two to four courses of the infusion therapy were given to each patient, and the response rate, the tumor and serum drug concentrations, and the cell kinetics in tumor tissue were evaluated. The response rate (CR+PR) was 71.4% according to the WHO criteria. There was no difference, in the tumor tissue concentrations of CDDP and BLM between responders and nonresponders. Although the DNA ploidy of tumor cells was not significantly different between the two groups before treatment, both the labeling index with BrdU and the proliferation index with flow cytometry significantly increased 24 hours after treatment in responding tumors but not in nonresponding tumors. These results show that intra-arterial infusion with CDDP and BLM improves the prognosis of recurrent cervical cancer and that labeling and proliferation indices may be useful for determining the response of cervical cancer to intra-arterial chemotherapy."} {"id": "PMID:1280403", "title": "Conditions associated with normal levels of prostate-specific antigen and elevation of prostatic acid phosphatase.", "content": "Thirteen cases are reported with normal levels of prostate-specific antigen and elevated prostatic acid phosphatase (PAP). Conditions that were associated with an elevated PAP were myeloproliferative syndromes (four cases), metastatic nonprostatic carcinoma (six cases), prostatic carcinoma (one case), tuberculosis with a concurrent lupus-like syndrome (one case), and osteomyelitis (one case). The inclusion of PAP in the initial investigation of cases with suspected prostatic disease results in a decreased specificity.", "contents": "Conditions associated with normal levels of prostate-specific antigen and elevation of prostatic acid phosphatase. Thirteen cases are reported with normal levels of prostate-specific antigen and elevated prostatic acid phosphatase (PAP). Conditions that were associated with an elevated PAP were myeloproliferative syndromes (four cases), metastatic nonprostatic carcinoma (six cases), prostatic carcinoma (one case), tuberculosis with a concurrent lupus-like syndrome (one case), and osteomyelitis (one case). The inclusion of PAP in the initial investigation of cases with suspected prostatic disease results in a decreased specificity."} {"id": "PMID:1280404", "title": "Hyperthermo-chemo-radiotherapy as a definitive treatment for patients with early esophageal carcinoma.", "content": "Ten patients with early stage esophageal carcinoma were treated with hyperthermo-chemo-radiotherapy (HCR) without surgery. The reasons for the inoperability of these patients included medically inoperable unresectable cancers, advanced age, and/or refusal to undergo surgery. The diagnosis of early esophageal carcinoma was determined by esophagograms, endoscopy, and ultrasonography. Squamous cell carcinoma was histopathologically confirmed in each case. Each patient underwent four to nine sessions of hyperthermic treatment combined with external irradiation and chemotherapy using bleomycin; eight of these patients received additional radiation, and two terminated treatment after the HCR therapy. The tumors in all patients showed either a complete response (CR) or a partial response (PR) after HCR therapy; in two patients viable cancer cells remained, but later disappeared after additional radiation. Five patients experienced no local recurrence for 12 to 70 months and are now alive and doing well, three died of other medical conditions without any evidence of esophageal cancer, and two died of recurrent esophageal cancer 20 to 27 months after initial admission. All ten patients tolerated the HCR well without any systemic side effects. However, in two patients, esophageal erosion was recognized endoscopically. HCR therapy therefore deserves serious consideration when treating patients with small malignant lesions of the esophagus who, for various reasons, are unable to undergo surgery.", "contents": "Hyperthermo-chemo-radiotherapy as a definitive treatment for patients with early esophageal carcinoma. Ten patients with early stage esophageal carcinoma were treated with hyperthermo-chemo-radiotherapy (HCR) without surgery. The reasons for the inoperability of these patients included medically inoperable unresectable cancers, advanced age, and/or refusal to undergo surgery. The diagnosis of early esophageal carcinoma was determined by esophagograms, endoscopy, and ultrasonography. Squamous cell carcinoma was histopathologically confirmed in each case. Each patient underwent four to nine sessions of hyperthermic treatment combined with external irradiation and chemotherapy using bleomycin; eight of these patients received additional radiation, and two terminated treatment after the HCR therapy. The tumors in all patients showed either a complete response (CR) or a partial response (PR) after HCR therapy; in two patients viable cancer cells remained, but later disappeared after additional radiation. Five patients experienced no local recurrence for 12 to 70 months and are now alive and doing well, three died of other medical conditions without any evidence of esophageal cancer, and two died of recurrent esophageal cancer 20 to 27 months after initial admission. All ten patients tolerated the HCR well without any systemic side effects. However, in two patients, esophageal erosion was recognized endoscopically. HCR therapy therefore deserves serious consideration when treating patients with small malignant lesions of the esophagus who, for various reasons, are unable to undergo surgery."} {"id": "PMID:1280405", "title": "The admission serum lipase:amylase ratio differentiates alcoholic from nonalcoholic acute pancreatitis.", "content": "To determine whether the lipase:amylase ratio differentiates alcoholic from nonalcoholic pancreatitis, we conducted a retrospective review of charts with the diagnosis of acute pancreatitis at the George Washington University Medical Center between January 1988 and July 1990. A total of 446 charts were reviewed. For a patient to be included in the subsequent analysis, the following criteria were met: 1) the patient had typical symptoms of pancreatitis, 2) serum amylase and lipase were analyzed on admission, and 3) a computerized tomographic (CT) scan or ultrasound of the abdomen was obtained within 72 h of admission. Forty-seven charts satisfied the requirements for inclusion in the study. Data collected from the charts included history of alcohol consumption, age, sex, race, admission serum amylase and serum lipase (from this the amylase:lipase ratio was calculated), peak serum amylase and serum lipase, and number of days of abdominal pain before admission. Patients with alcoholic pancreatitis had significantly lower serum amylase levels and significantly higher lipase:amylase ratios than those with nonalcoholic pancreatitis (p < 0.01). There was no difference in the serum lipase between the groups. The higher the lipase:amylase ratio, the greater the specificity of alcohol as the etiology of acute pancreatitis. Only patients with alcoholic acute pancreatitis had lipase:amylase ratios > 5.0 (sensitivity 31%, specificity 100%). Our data point to the clinical utility of the lipase:amylase ratio in differentiating alcoholic from nonalcoholic acute pancreatitis. Prospective studies will be needed to confirm the clinical utility of this ratio.", "contents": "The admission serum lipase:amylase ratio differentiates alcoholic from nonalcoholic acute pancreatitis. To determine whether the lipase:amylase ratio differentiates alcoholic from nonalcoholic pancreatitis, we conducted a retrospective review of charts with the diagnosis of acute pancreatitis at the George Washington University Medical Center between January 1988 and July 1990. A total of 446 charts were reviewed. For a patient to be included in the subsequent analysis, the following criteria were met: 1) the patient had typical symptoms of pancreatitis, 2) serum amylase and lipase were analyzed on admission, and 3) a computerized tomographic (CT) scan or ultrasound of the abdomen was obtained within 72 h of admission. Forty-seven charts satisfied the requirements for inclusion in the study. Data collected from the charts included history of alcohol consumption, age, sex, race, admission serum amylase and serum lipase (from this the amylase:lipase ratio was calculated), peak serum amylase and serum lipase, and number of days of abdominal pain before admission. Patients with alcoholic pancreatitis had significantly lower serum amylase levels and significantly higher lipase:amylase ratios than those with nonalcoholic pancreatitis (p < 0.01). There was no difference in the serum lipase between the groups. The higher the lipase:amylase ratio, the greater the specificity of alcohol as the etiology of acute pancreatitis. Only patients with alcoholic acute pancreatitis had lipase:amylase ratios > 5.0 (sensitivity 31%, specificity 100%). Our data point to the clinical utility of the lipase:amylase ratio in differentiating alcoholic from nonalcoholic acute pancreatitis. Prospective studies will be needed to confirm the clinical utility of this ratio."} {"id": "PMID:1280406", "title": "Des-gamma-carboxy prothrombin (PIVKA-II) and alpha-fetoprotein-producing IIc-type early gastric cancer.", "content": "We describe the case of a 56-yr-old man with primary gastric adenocarcinoma, who had an extremely high plasma level of des-gamma-carboxy prothrombin (2.45 AU/ml) and of serum alpha-fetoprotein (2810 ng/ml). Histopathologically, the gastric cancer was a IIc type of early cancer which consisted of a combination of a poorly differentiated adenocarcinoma and a well-differentiated tubular adenocarcinoma. The association of a hepatic tumor including hepatocellular carcinoma or liver metastasis was ruled out by ultrasonography, computed tomography, radiocolloid liver scan, magnetic resonance imaging, and angiography. Foci strongly resembling hepatocellular carcinoma (hepatoid differentiation) were noted in the gastric tumor. Localization of des-gamma-carboxy prothrombin and alpha-fetoprotein within the tumor cells, especially within the hepatoid differentiated foci, was demonstrated by the immunohistochemical staining of tissue obtained at biopsy and the resected specimen. This case seems to be the first case reported in which des-gamma-carboxy prothrombin was produced by the gastric cancer. This finding supports the theory of hepatoid differentiation of a gastric cancer.", "contents": "Des-gamma-carboxy prothrombin (PIVKA-II) and alpha-fetoprotein-producing IIc-type early gastric cancer. We describe the case of a 56-yr-old man with primary gastric adenocarcinoma, who had an extremely high plasma level of des-gamma-carboxy prothrombin (2.45 AU/ml) and of serum alpha-fetoprotein (2810 ng/ml). Histopathologically, the gastric cancer was a IIc type of early cancer which consisted of a combination of a poorly differentiated adenocarcinoma and a well-differentiated tubular adenocarcinoma. The association of a hepatic tumor including hepatocellular carcinoma or liver metastasis was ruled out by ultrasonography, computed tomography, radiocolloid liver scan, magnetic resonance imaging, and angiography. Foci strongly resembling hepatocellular carcinoma (hepatoid differentiation) were noted in the gastric tumor. Localization of des-gamma-carboxy prothrombin and alpha-fetoprotein within the tumor cells, especially within the hepatoid differentiated foci, was demonstrated by the immunohistochemical staining of tissue obtained at biopsy and the resected specimen. This case seems to be the first case reported in which des-gamma-carboxy prothrombin was produced by the gastric cancer. This finding supports the theory of hepatoid differentiation of a gastric cancer."} {"id": "PMID:1280407", "title": "Audiologic profiles of children with Kawasaki disease.", "content": "Kawasaki disease (KD) is an idiopathic vasculitis associated with systemic inflammation and profound immunoregulatory changes. Recent reports from Japan and the United States have documented the association of sensorineural hearing loss (SNHL) with acute KD. To further characterize the nature and prevalence of this complication, we prospectively evaluated the hearing of 40 consecutive patients with acute KD at a single institution. Standard audiometric procedures were used, including visual reinforcement audiometry and play audiometry. Auditory brainstem response (ABR) testing using clicks and tone pips (1000-4000 Hz) was performed in patients with abnormal or unreliable results on behavioral audiometry. Acoustic immittance measurements were obtained on all patients. Of the 23 males and 17 females (mean age 3.2 +/- 2.3 years, range 0.6-11.1 years), all but three were evaluated and treated with aspirin and intravenous gama globulin within 1 month of onset of fever. Seven children had test results suggesting sensorineural threshold shifts, 16 had normal hearing, and 14 had inconclusive hearing evaluations. Laboratory data in patients with hearing threshold shifts revealed significantly longer duration of fever (4.1 +/- 1.0 versus 1.9 +/- 0.5 days), and a tendency for higher temperatures and white blood cell counts at diagnosis compared to those with normal hearing. Results suggest that transient as well as persistent SNHL may be associated with the acute vasculitis of KD, and may be associated with laboratory markers indicating more severe systemic inflammation. Audiologic screening should be considered for all patients following KD.", "contents": "Audiologic profiles of children with Kawasaki disease. Kawasaki disease (KD) is an idiopathic vasculitis associated with systemic inflammation and profound immunoregulatory changes. Recent reports from Japan and the United States have documented the association of sensorineural hearing loss (SNHL) with acute KD. To further characterize the nature and prevalence of this complication, we prospectively evaluated the hearing of 40 consecutive patients with acute KD at a single institution. Standard audiometric procedures were used, including visual reinforcement audiometry and play audiometry. Auditory brainstem response (ABR) testing using clicks and tone pips (1000-4000 Hz) was performed in patients with abnormal or unreliable results on behavioral audiometry. Acoustic immittance measurements were obtained on all patients. Of the 23 males and 17 females (mean age 3.2 +/- 2.3 years, range 0.6-11.1 years), all but three were evaluated and treated with aspirin and intravenous gama globulin within 1 month of onset of fever. Seven children had test results suggesting sensorineural threshold shifts, 16 had normal hearing, and 14 had inconclusive hearing evaluations. Laboratory data in patients with hearing threshold shifts revealed significantly longer duration of fever (4.1 +/- 1.0 versus 1.9 +/- 0.5 days), and a tendency for higher temperatures and white blood cell counts at diagnosis compared to those with normal hearing. Results suggest that transient as well as persistent SNHL may be associated with the acute vasculitis of KD, and may be associated with laboratory markers indicating more severe systemic inflammation. Audiologic screening should be considered for all patients following KD."} {"id": "PMID:1280408", "title": "Childhood peripheral neuropathy with autoantibodies to myelin glycoprotein P0.", "content": "The serum of a 4-year-old child with severe hypertrophic peripheral neuropathy contained high-titer polyclonal antibodies, mainly of IgG class, reacting with the 30-kd P0 glycoprotein of peripheral nerve. This was demonstrated by indirect immunofluorescence, immunoblot analysis of myelin proteins, and enzyme-linked immunosorbent assay with purified P0 glycoprotein. The antibodies did not react with myelin-associated glycoprotein, sulfated glycuronic acid-containing paragloboside (SGPG and SGLPG), or other peripheral nerve glycolipids or gangliosides. To our knowledge this is the first report of strong antibody activity specifically directed against P0. This antibody may play a causative role in the pathogenesis of the peripheral neuropathy in this patient.", "contents": "Childhood peripheral neuropathy with autoantibodies to myelin glycoprotein P0. The serum of a 4-year-old child with severe hypertrophic peripheral neuropathy contained high-titer polyclonal antibodies, mainly of IgG class, reacting with the 30-kd P0 glycoprotein of peripheral nerve. This was demonstrated by indirect immunofluorescence, immunoblot analysis of myelin proteins, and enzyme-linked immunosorbent assay with purified P0 glycoprotein. The antibodies did not react with myelin-associated glycoprotein, sulfated glycuronic acid-containing paragloboside (SGPG and SGLPG), or other peripheral nerve glycolipids or gangliosides. To our knowledge this is the first report of strong antibody activity specifically directed against P0. This antibody may play a causative role in the pathogenesis of the peripheral neuropathy in this patient."} {"id": "PMID:1280409", "title": "[Histopathology and ultrastructure of opportunistic infections of the digestive tract in acquired immunodeficiency syndrome].", "content": "Light and electron microscopy studies of digestive tract biopsy specimens from AIDS patients are very useful for the detection of opportunistic pathogens which may be located in: the lumen (bacteria, Candida albicans, Giardia lamblia), enterocyte brush border (Cryptosporidium sp), enterocyte cytoplasm (Enterocytozoon bieneusi), enterocyte nuclei (cytomegalovirus), or cytoplasm of lamina propria macrophages (Mycobacterium avium intracellulare). These studies may also be useful to detect combinations of morbid conditions and to evaluate the effectiveness (if any) of therapeutic agents.", "contents": "[Histopathology and ultrastructure of opportunistic infections of the digestive tract in acquired immunodeficiency syndrome]. Light and electron microscopy studies of digestive tract biopsy specimens from AIDS patients are very useful for the detection of opportunistic pathogens which may be located in: the lumen (bacteria, Candida albicans, Giardia lamblia), enterocyte brush border (Cryptosporidium sp), enterocyte cytoplasm (Enterocytozoon bieneusi), enterocyte nuclei (cytomegalovirus), or cytoplasm of lamina propria macrophages (Mycobacterium avium intracellulare). These studies may also be useful to detect combinations of morbid conditions and to evaluate the effectiveness (if any) of therapeutic agents."} {"id": "PMID:1280410", "title": "Fontan procedure for hypoplastic left heart syndrome.", "content": "Since 1985, 354 neonates have undergone palliative reconstruction for hypoplastic left heart syndrome with 109 early deaths and 12 late deaths. Of the survivors, before 1989, 77 patients underwent a subsequent modified Fontan operation, consisting of baffling the atrial septal defect to the tricuspid valve (initial 25 patients) or intraatrial baffling of the inferior vena cava to the pulmonary arteries and superior vena cava (52 patients). There were 17 early deaths and three late deaths. Major serous effusions developed in 42 patients (54%) after Fontan operation. Since 1989, a staged approach to Fontan's operation was undertaken in an effort to reduce the volume load of the right ventricle as early as possible, to minimize the impact of rapid changes in ventricular geometry and diastolic function that can accompany a primary Fontan operation, and to reduce effusive complications. Thus, at a mean age of 6 months, 121 patients have undergone closure of aortopulmonary shunt, augmentation of central pulmonary arteries, and association of the superior vena cava with the branch pulmonary arteries (hemi-Fontan procedure). Of these, 61 patients have already undergone completion of the Fontan procedure with six early deaths and three late deaths. Major serous effusions developed in 28 patients (46%) with the staged Fontan. For perspective, the contemporary experience since January 1991 consists of 58 neonates who have undergone initial palliation with 11 deaths (19%), 17 patients who have undergone the hemi-Fontan procedure with one death (6%), and 21 patients who have undergone completion of the Fontan operation with one death (5%).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Fontan procedure for hypoplastic left heart syndrome. Since 1985, 354 neonates have undergone palliative reconstruction for hypoplastic left heart syndrome with 109 early deaths and 12 late deaths. Of the survivors, before 1989, 77 patients underwent a subsequent modified Fontan operation, consisting of baffling the atrial septal defect to the tricuspid valve (initial 25 patients) or intraatrial baffling of the inferior vena cava to the pulmonary arteries and superior vena cava (52 patients). There were 17 early deaths and three late deaths. Major serous effusions developed in 42 patients (54%) after Fontan operation. Since 1989, a staged approach to Fontan's operation was undertaken in an effort to reduce the volume load of the right ventricle as early as possible, to minimize the impact of rapid changes in ventricular geometry and diastolic function that can accompany a primary Fontan operation, and to reduce effusive complications. Thus, at a mean age of 6 months, 121 patients have undergone closure of aortopulmonary shunt, augmentation of central pulmonary arteries, and association of the superior vena cava with the branch pulmonary arteries (hemi-Fontan procedure). Of these, 61 patients have already undergone completion of the Fontan procedure with six early deaths and three late deaths. Major serous effusions developed in 28 patients (46%) with the staged Fontan. For perspective, the contemporary experience since January 1991 consists of 58 neonates who have undergone initial palliation with 11 deaths (19%), 17 patients who have undergone the hemi-Fontan procedure with one death (6%), and 21 patients who have undergone completion of the Fontan operation with one death (5%).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280411", "title": "Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study.", "content": "We tested the efficacy and safety of aprotinin in 169 patients undergoing isolated reoperative myocardial revascularization. Patients were randomly assigned to high-dose aprotinin, low-dose aprotinin, or placebo treatment groups in a double-blind, placebo-controlled study. Treatment groups did not differ significantly with respect to age, sex, red cell mass, number of grafts, use of internal thoracic artery, or incidence of preoperative aspirin therapy. Patients treated with aprotinin had a significant reduction in postoperative chest tube drainage (720 +/- 753, 866 +/- 1,636, and 1,121 +/- 683 mL, respectively, for high-dose aprotinin, low-dose aprotinin, and placebo; p < 0.001). Transfusion requirements were reduced in aprotinin-treated patients (2.1 +/- 4.2, 4.8 +/- 11.8, and 4.1 +/- 6.2 units for high-dose, low-dose, and placebo, respectively; p < 0.001). A similar reduction in chest tube drainage and transfusion requirements was seen in patients using aspirin preoperatively. Q-wave myocardial infarctions were increased in the aprotinin subgroups (17.5%, 14.3%, and 8.9% for high-dose, low-dose, and placebo groups; not significant). Acute vein graft thrombosis was found in six of 12 vein grafts studied at postmortem examination in patients receiving aprotinin but not in any of five grafts in patients receiving placebo. We conclude that aprotinin is extremely effective in reducing bleeding and transfusion requirements and may increase the risk of graft thrombosis.", "contents": "Aprotinin therapy for reoperative myocardial revascularization: a placebo-controlled study. We tested the efficacy and safety of aprotinin in 169 patients undergoing isolated reoperative myocardial revascularization. Patients were randomly assigned to high-dose aprotinin, low-dose aprotinin, or placebo treatment groups in a double-blind, placebo-controlled study. Treatment groups did not differ significantly with respect to age, sex, red cell mass, number of grafts, use of internal thoracic artery, or incidence of preoperative aspirin therapy. Patients treated with aprotinin had a significant reduction in postoperative chest tube drainage (720 +/- 753, 866 +/- 1,636, and 1,121 +/- 683 mL, respectively, for high-dose aprotinin, low-dose aprotinin, and placebo; p < 0.001). Transfusion requirements were reduced in aprotinin-treated patients (2.1 +/- 4.2, 4.8 +/- 11.8, and 4.1 +/- 6.2 units for high-dose, low-dose, and placebo, respectively; p < 0.001). A similar reduction in chest tube drainage and transfusion requirements was seen in patients using aspirin preoperatively. Q-wave myocardial infarctions were increased in the aprotinin subgroups (17.5%, 14.3%, and 8.9% for high-dose, low-dose, and placebo groups; not significant). Acute vein graft thrombosis was found in six of 12 vein grafts studied at postmortem examination in patients receiving aprotinin but not in any of five grafts in patients receiving placebo. We conclude that aprotinin is extremely effective in reducing bleeding and transfusion requirements and may increase the risk of graft thrombosis."} {"id": "PMID:1280412", "title": "Low-dose aprotinin in internal mammary artery bypass operations contributes to important blood saving.", "content": "The effect on postoperative blood loss and blood use of blood-saving treatment with or without 280 mg of low-dose aprotinin (2 million kallikrein inactivator units) was studied in 200 consecutive patients undergoing either unilateral or bilateral internal mammary artery bypass grafting. Postoperative blood loss and total units of homologous blood products were similar in patients having either bypass procedure without aprotinin treatment. In patients given aprotinin, postoperative blood loss and use of homologous blood products were significantly lower (p < 0.05). The use of any donor blood product was prevented in 78% of the patients given aprotinin versus only 45% of patients treated without aprotinin. None of the aprotinin-treated patients underwent repeat thoracotomy for excessive bleeding; repeat thoracotomy was indicated in 8% of the patients having bilateral internal mammary artery grafting without aprotinin treatment. These results demonstrate that low-dose aprotinin reduces blood loss and blood use significantly and prevents excessive bleeding.", "contents": "Low-dose aprotinin in internal mammary artery bypass operations contributes to important blood saving. The effect on postoperative blood loss and blood use of blood-saving treatment with or without 280 mg of low-dose aprotinin (2 million kallikrein inactivator units) was studied in 200 consecutive patients undergoing either unilateral or bilateral internal mammary artery bypass grafting. Postoperative blood loss and total units of homologous blood products were similar in patients having either bypass procedure without aprotinin treatment. In patients given aprotinin, postoperative blood loss and use of homologous blood products were significantly lower (p < 0.05). The use of any donor blood product was prevented in 78% of the patients given aprotinin versus only 45% of patients treated without aprotinin. None of the aprotinin-treated patients underwent repeat thoracotomy for excessive bleeding; repeat thoracotomy was indicated in 8% of the patients having bilateral internal mammary artery grafting without aprotinin treatment. These results demonstrate that low-dose aprotinin reduces blood loss and blood use significantly and prevents excessive bleeding."} {"id": "PMID:1280413", "title": "[Treatment and staining of smears and sections for detection of microorganisms].", "content": "Detection of bacteria in smears and sections is necessary for a proper diagnosis of infectious diseases. Main methods of staining for a light- and luminescent microscopy and prescriptions of the dye preparation are presented.", "contents": "[Treatment and staining of smears and sections for detection of microorganisms]. Detection of bacteria in smears and sections is necessary for a proper diagnosis of infectious diseases. Main methods of staining for a light- and luminescent microscopy and prescriptions of the dye preparation are presented."} {"id": "PMID:1280414", "title": "Synthesis and characterization of rat interleukin-10 (IL-10) cDNA clones from the RNA of cultured OX8- OX22- thoracic duct T cells.", "content": "A cDNA of the complete coding region of rat IL-10 was cloned and sequenced using RNA isolated from a cultured population of thoracic duct T-lymphocytes obtained from Trichinella spiralis infected animals. The OX8- OX22-T-helper cells were stimulated in vitro with Concanavalin A for 24 hours prior to harvest. Reverse transcription of cellular RNA was primed with oligo-dT followed by amplification of IL-10 specific cDNA by polymerase chain reaction with synthetic oligo nucleotide primers chosen from two highly conserved regions of mouse and human IL-10. The sequence of the coding region of the amplified, cloned rat IL-10 cDNA is 90% identical to the mouse and 82% identical to the human IL-10 cDNA coding regions.", "contents": "Synthesis and characterization of rat interleukin-10 (IL-10) cDNA clones from the RNA of cultured OX8- OX22- thoracic duct T cells. A cDNA of the complete coding region of rat IL-10 was cloned and sequenced using RNA isolated from a cultured population of thoracic duct T-lymphocytes obtained from Trichinella spiralis infected animals. The OX8- OX22-T-helper cells were stimulated in vitro with Concanavalin A for 24 hours prior to harvest. Reverse transcription of cellular RNA was primed with oligo-dT followed by amplification of IL-10 specific cDNA by polymerase chain reaction with synthetic oligo nucleotide primers chosen from two highly conserved regions of mouse and human IL-10. The sequence of the coding region of the amplified, cloned rat IL-10 cDNA is 90% identical to the mouse and 82% identical to the human IL-10 cDNA coding regions."} {"id": "PMID:1280415", "title": "Functional study of the germinal angiotensin I-converting enzyme promoter.", "content": "Polymerase chain amplification experiments indicate that the germinal specific promoter of the angiotensin I-converting enzyme (ACE) is completely extinguished in somatic tissues. Despite this very strict specificity of expression, the germinal ACE promoter is active in transient transfection experiments in two somatic cell lines and one cell line of germinal origin. The analysis of the promoter shows the existence two regulatory elements within the first 350 bp: a proximal positive element and a distal negative element.", "contents": "Functional study of the germinal angiotensin I-converting enzyme promoter. Polymerase chain amplification experiments indicate that the germinal specific promoter of the angiotensin I-converting enzyme (ACE) is completely extinguished in somatic tissues. Despite this very strict specificity of expression, the germinal ACE promoter is active in transient transfection experiments in two somatic cell lines and one cell line of germinal origin. The analysis of the promoter shows the existence two regulatory elements within the first 350 bp: a proximal positive element and a distal negative element."} {"id": "PMID:1280416", "title": "Loss of collagenase gene expression in immortalized clones of SV40 T antigen-transformed human diploid fibroblasts.", "content": "We isolated a cDNA clone whose expression was lost during immortalization. The subtractive hybridization was performed between a genetically matched pair of mortal and immortal lines of SV40 T antigen-transformed MRC-5. The clone was found to code human interstitial collagenase. The expression of collagenase gene was almost completely shut off in seven out of eight independent immortalized clones. In addition, the levels of collagenase expression were dramatically increased toward crisis in the T antigen-transformed but mortal cells. These findings suggest the possibility that the regulatory mechanism of collagenase expression is related to both processes of in vitro aging and immortalization.", "contents": "Loss of collagenase gene expression in immortalized clones of SV40 T antigen-transformed human diploid fibroblasts. We isolated a cDNA clone whose expression was lost during immortalization. The subtractive hybridization was performed between a genetically matched pair of mortal and immortal lines of SV40 T antigen-transformed MRC-5. The clone was found to code human interstitial collagenase. The expression of collagenase gene was almost completely shut off in seven out of eight independent immortalized clones. In addition, the levels of collagenase expression were dramatically increased toward crisis in the T antigen-transformed but mortal cells. These findings suggest the possibility that the regulatory mechanism of collagenase expression is related to both processes of in vitro aging and immortalization."} {"id": "PMID:1280417", "title": "cDNA cloning and sequence determination of the pheromone biosynthesis activating neuropeptide of the silkworm, Bombyx mori.", "content": "We have identified the cDNAs encoding pheromone biosynthesis activating neuropeptide (PBAN) using PCR technique. The nucleotide sequence showed that the PBAN gene encodes, besides PBAN, diapause hormone and three putative amidated peptides. These four peptides share with PBAN the C-terminal pentapeptide amide which is corresponding to the shortest fragment with pheromonotropic activity. The organization of the PBAN gene is characteristic of several short neuropeptides and has some degree of similarity to that of the gene for the insect neuropeptide FMRFamide. Thus, the PBAN gene products construct a family of structurally related peptides and have various biological functions.", "contents": "cDNA cloning and sequence determination of the pheromone biosynthesis activating neuropeptide of the silkworm, Bombyx mori. We have identified the cDNAs encoding pheromone biosynthesis activating neuropeptide (PBAN) using PCR technique. The nucleotide sequence showed that the PBAN gene encodes, besides PBAN, diapause hormone and three putative amidated peptides. These four peptides share with PBAN the C-terminal pentapeptide amide which is corresponding to the shortest fragment with pheromonotropic activity. The organization of the PBAN gene is characteristic of several short neuropeptides and has some degree of similarity to that of the gene for the insect neuropeptide FMRFamide. Thus, the PBAN gene products construct a family of structurally related peptides and have various biological functions."} {"id": "PMID:1280418", "title": "Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine.", "content": "The objective of this study was to determine whether constitutive nitric oxide (NO) synthase from rat cerebellum could be regulated by the two products of the reaction, NO and L-citrulline, utilizing L-arginine as substrate. NO synthase activity was determined by monitoring the formation of 3H-citrulline from 3H-L-arginine in the presence of added cofactors. The rate of citrulline formation in enzyme reaction mixtures was non-linear. Addition of superoxide dismutase (SOD; 100 units) inhibited NO synthase activity and made the rate of product formation more non-linear, whereas addition of oxyhemoglobin (HbO2; 30 microM) increased NO synthase activity, made the rate of product formation linear and also abolished the effect of SOD. Added NO (10 microM) inhibited NO synthase activity and this inhibition was potentiated by SOD and abolished by HbO2. Added L-citrulline (1 mM) did not alter NO synthase activity. The two NO donors, S-nitroso-N-acetylpenicillamine (200 microM) and N-methyl-N'-nitro-N-nitrosoguanidine (200 microM) mimicked the inhibitory effect of NO and inhibition of NO synthase activity by NO was reversible. These observations indicate clearly that NO formed during the NO synthase reaction or added to the enzyme reaction mixture causes a reversible inhibition of NO synthase activity. Thus, NO may function as a negative feedback modulator of its own synthesis.", "contents": "Constitutive nitric oxide synthase from cerebellum is reversibly inhibited by nitric oxide formed from L-arginine. The objective of this study was to determine whether constitutive nitric oxide (NO) synthase from rat cerebellum could be regulated by the two products of the reaction, NO and L-citrulline, utilizing L-arginine as substrate. NO synthase activity was determined by monitoring the formation of 3H-citrulline from 3H-L-arginine in the presence of added cofactors. The rate of citrulline formation in enzyme reaction mixtures was non-linear. Addition of superoxide dismutase (SOD; 100 units) inhibited NO synthase activity and made the rate of product formation more non-linear, whereas addition of oxyhemoglobin (HbO2; 30 microM) increased NO synthase activity, made the rate of product formation linear and also abolished the effect of SOD. Added NO (10 microM) inhibited NO synthase activity and this inhibition was potentiated by SOD and abolished by HbO2. Added L-citrulline (1 mM) did not alter NO synthase activity. The two NO donors, S-nitroso-N-acetylpenicillamine (200 microM) and N-methyl-N'-nitro-N-nitrosoguanidine (200 microM) mimicked the inhibitory effect of NO and inhibition of NO synthase activity by NO was reversible. These observations indicate clearly that NO formed during the NO synthase reaction or added to the enzyme reaction mixture causes a reversible inhibition of NO synthase activity. Thus, NO may function as a negative feedback modulator of its own synthesis."} {"id": "PMID:1280419", "title": "Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization.", "content": "The receptors for the brain and gastrointestinal peptide, cholecystokinin, can be classified into CCKA and CCKB subtypes. Having recently cloned the rat CCKB receptor, we used it's cDNA to isolate the human CCKB receptor homologue from brain and stomach which encodes a 447 amino acid protein with 90% identity to both rat CCKB and canine gastrin receptors. Northern hybridization identifies transcripts from stomach, pancreas, brain and gallbladder. The CCKB receptor gene maps to chromosome 11. Expression of the receptor cDNA in COS-7 cells was characteristic of a CCKB receptor subtype pharmacology. These data confirm that we have cloned a novel gene for the human brain and stomach CCKB receptor.", "contents": "Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal localization. The receptors for the brain and gastrointestinal peptide, cholecystokinin, can be classified into CCKA and CCKB subtypes. Having recently cloned the rat CCKB receptor, we used it's cDNA to isolate the human CCKB receptor homologue from brain and stomach which encodes a 447 amino acid protein with 90% identity to both rat CCKB and canine gastrin receptors. Northern hybridization identifies transcripts from stomach, pancreas, brain and gallbladder. The CCKB receptor gene maps to chromosome 11. Expression of the receptor cDNA in COS-7 cells was characteristic of a CCKB receptor subtype pharmacology. These data confirm that we have cloned a novel gene for the human brain and stomach CCKB receptor."} {"id": "PMID:1280420", "title": "Cancer cell binding to E-selectin transfected human endothelia.", "content": "Human endothelial cells were transiently transfected with E-Selectin which enabled us to study tumor cell/endothelial interactions following engagement of E-Selectin without the added complications of metabolic stimulation, morphological changes, and/or up regulation of other adhesion molecules due to cytokine induction. Similar results were received from in vitro binding studies and FACS analyses on both Tumor Necrosis Factor-alpha activated and E-Selectin transfected endothelial cells. These data suggest that this methodology is appropriate for dissecting the individual activities of E-selectin while minimizing the participation of other adhesion molecules, thereby allowing us to develop a better understanding of the role of E-Selectin and endothelia in metastatic disease.", "contents": "Cancer cell binding to E-selectin transfected human endothelia. Human endothelial cells were transiently transfected with E-Selectin which enabled us to study tumor cell/endothelial interactions following engagement of E-Selectin without the added complications of metabolic stimulation, morphological changes, and/or up regulation of other adhesion molecules due to cytokine induction. Similar results were received from in vitro binding studies and FACS analyses on both Tumor Necrosis Factor-alpha activated and E-Selectin transfected endothelial cells. These data suggest that this methodology is appropriate for dissecting the individual activities of E-selectin while minimizing the participation of other adhesion molecules, thereby allowing us to develop a better understanding of the role of E-Selectin and endothelia in metastatic disease."} {"id": "PMID:1280421", "title": "Expression of DRG during murine embryonic development.", "content": "We had previously characterised a cDNA which encodes a novel GTP-binding protein DRG. The expression of drg gene is down-regulated during the embryonic development of murine central nervous system. Further analysis of drg mRNA and protein in adult mouse tissues and various cell lines of different origins indicated that it is expressed widely, albeit at low and variable levels. In situ hybridisation analysis of mRNA expression in sections of mouse embryos indicated that drg is expressed strongly in various embryonic tissues. The expression of drg mRNA is greatly reduced in newborn animals. At cellular level, DRG protein can be detected in the cytoplasm. These observations suggest that DRG may play multiple roles in development and normal cell metabolism.", "contents": "Expression of DRG during murine embryonic development. We had previously characterised a cDNA which encodes a novel GTP-binding protein DRG. The expression of drg gene is down-regulated during the embryonic development of murine central nervous system. Further analysis of drg mRNA and protein in adult mouse tissues and various cell lines of different origins indicated that it is expressed widely, albeit at low and variable levels. In situ hybridisation analysis of mRNA expression in sections of mouse embryos indicated that drg is expressed strongly in various embryonic tissues. The expression of drg mRNA is greatly reduced in newborn animals. At cellular level, DRG protein can be detected in the cytoplasm. These observations suggest that DRG may play multiple roles in development and normal cell metabolism."} {"id": "PMID:1280422", "title": "Hepatocyte growth factor down-regulates the alpha-fetoprotein gene expression in PLC/PRF/5 human hepatoma cells.", "content": "Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes; however, in certain human hepatoma cell lines, the growth is inhibited by HGF. In the present study, the effect of HGF on the alpha-fetoprotein (AFP) gene expression was analyzed in PLC/PRF/5 human hepatoma cells. HGF did not inhibit cell proliferation, but dose-dependently suppressed AFP secretion at the concentrations of 10 ng/ml or less. By Northern blot analysis, the levels of AFP mRNA were suppressed by HGF, whereas the levels of beta-actin mRNA used as a control did not show any significant changes. In the transient chloramphenicol acetyltransferase plasmid transfection assays, the AFP promoter activity was repressed by HGF, in contrast, the AFP enhancer activity was not affected by HGF. These results suggest that the AFP gene expression is down-regulated by HGF through the suppression of its promoter activity in human hepatoma cells.", "contents": "Hepatocyte growth factor down-regulates the alpha-fetoprotein gene expression in PLC/PRF/5 human hepatoma cells. Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes; however, in certain human hepatoma cell lines, the growth is inhibited by HGF. In the present study, the effect of HGF on the alpha-fetoprotein (AFP) gene expression was analyzed in PLC/PRF/5 human hepatoma cells. HGF did not inhibit cell proliferation, but dose-dependently suppressed AFP secretion at the concentrations of 10 ng/ml or less. By Northern blot analysis, the levels of AFP mRNA were suppressed by HGF, whereas the levels of beta-actin mRNA used as a control did not show any significant changes. In the transient chloramphenicol acetyltransferase plasmid transfection assays, the AFP promoter activity was repressed by HGF, in contrast, the AFP enhancer activity was not affected by HGF. These results suggest that the AFP gene expression is down-regulated by HGF through the suppression of its promoter activity in human hepatoma cells."} {"id": "PMID:1280423", "title": "Possible activity of acidic fibroblast growth factor as a progression factor rather than a transforming factor.", "content": "Acidic and basic fibroblast growth factors (aFGF and bFGF) are mitogens for mesoderm- and neuroectoderm-derived cells. The facts that FGF-related proteins are oncogenic and that FGFs are expressed in a variety of tumor cell lines or tumor tissues suggest the transforming activities of FGFs. To examine such an activity of aFGF, we introduced a human aFGF expression vector into two populations of Rat-1 cells; one was non-transformed (nRat-1), the other was partially-transformed (tRat-1). tRat-1 cells transfected with aFGF cDNA formed larger colonies in soft agar and produced larger and more malignant tumors in nude mice than those of parental cells. In contrast, nRat-1 cells transfected with aFGF cDNA neither formed colonies in soft agar nor produced tumors in nude mice. Our results suggest that high expression of aFGF may enhance a tumorigenic potential of Rat-1 cells rather than confer such a potential de novo.", "contents": "Possible activity of acidic fibroblast growth factor as a progression factor rather than a transforming factor. Acidic and basic fibroblast growth factors (aFGF and bFGF) are mitogens for mesoderm- and neuroectoderm-derived cells. The facts that FGF-related proteins are oncogenic and that FGFs are expressed in a variety of tumor cell lines or tumor tissues suggest the transforming activities of FGFs. To examine such an activity of aFGF, we introduced a human aFGF expression vector into two populations of Rat-1 cells; one was non-transformed (nRat-1), the other was partially-transformed (tRat-1). tRat-1 cells transfected with aFGF cDNA formed larger colonies in soft agar and produced larger and more malignant tumors in nude mice than those of parental cells. In contrast, nRat-1 cells transfected with aFGF cDNA neither formed colonies in soft agar nor produced tumors in nude mice. Our results suggest that high expression of aFGF may enhance a tumorigenic potential of Rat-1 cells rather than confer such a potential de novo."} {"id": "PMID:1280424", "title": "Purification of a mammary-derived growth inhibitor (MDGI) related polypeptide expressed during pregnancy.", "content": "The present study was undertaken to screen immunochemically for MDGI-related proteins in the mammary gland. A new form, MDGI 2, not present in lactation could be detected in the bovine gland during pregnancy. It was further distinguished from MDGI by its lower molecular weight, its association with a complex binding to WGA, and by lacking immunoreactivity to an anti-MDGI antibody directed against the C-terminus of MDGI. MDGI 2 was purified by chromatography over DEAE-Sepharose, Bio-Gel P-30 in 1% acetic acid, Sephacryl S-200 in 6 M urea and Mono Q. Final purification included HPLC on TSK G-3000 SW and electroelution from SDS-gels. Cell-free translation of poly (A+)mRNA from glands of pregnant animal yielded one form identical with MDGI. We assume that posttranslational processing of MDGI is involved in its activities.", "contents": "Purification of a mammary-derived growth inhibitor (MDGI) related polypeptide expressed during pregnancy. The present study was undertaken to screen immunochemically for MDGI-related proteins in the mammary gland. A new form, MDGI 2, not present in lactation could be detected in the bovine gland during pregnancy. It was further distinguished from MDGI by its lower molecular weight, its association with a complex binding to WGA, and by lacking immunoreactivity to an anti-MDGI antibody directed against the C-terminus of MDGI. MDGI 2 was purified by chromatography over DEAE-Sepharose, Bio-Gel P-30 in 1% acetic acid, Sephacryl S-200 in 6 M urea and Mono Q. Final purification included HPLC on TSK G-3000 SW and electroelution from SDS-gels. Cell-free translation of poly (A+)mRNA from glands of pregnant animal yielded one form identical with MDGI. We assume that posttranslational processing of MDGI is involved in its activities."} {"id": "PMID:1280425", "title": "Increased mitochondrial activities in pigmented (melanized) fish cells and nucleotide sequence of mitochondrial large rRNA.", "content": "Using the subtracted probe approach, we had previously isolated eight cDNAs whose corresponding RNAs are more abundant in pigmented (melanized) than in closely related unpigmented goldfish cell lines. We report here that two of these are of mitochondrial origin, suggesting that pigmentation is accompanied by higher content (activity) of mitochondria. We also present the complete nucleotide sequence of the full length cDNA for the large mitochondrial rRNA, showing the presence of a polyA tail, two polyadenylation signals and a long open reading frame potentially encoding for a polypeptide of 166 amino acids and with no known protein homologue. It is however unknown whether such a polypeptide is actually produced.", "contents": "Increased mitochondrial activities in pigmented (melanized) fish cells and nucleotide sequence of mitochondrial large rRNA. Using the subtracted probe approach, we had previously isolated eight cDNAs whose corresponding RNAs are more abundant in pigmented (melanized) than in closely related unpigmented goldfish cell lines. We report here that two of these are of mitochondrial origin, suggesting that pigmentation is accompanied by higher content (activity) of mitochondria. We also present the complete nucleotide sequence of the full length cDNA for the large mitochondrial rRNA, showing the presence of a polyA tail, two polyadenylation signals and a long open reading frame potentially encoding for a polypeptide of 166 amino acids and with no known protein homologue. It is however unknown whether such a polypeptide is actually produced."} {"id": "PMID:1280426", "title": "Methylation-sensitive protein-DNA interaction at the cell cycle regulatory domain of human thymidine kinase promoter.", "content": "We have investigated the DNA-protein complex formation in nuclear extracts of human cells using the sequence of cell-cycle regulatory unit (CCRU) of human thymidine kinase (TK) promoter. It appeared that a distinct DNA-protein complex was present in three human tumor cell lines and that the CCAAT box within the sequence of CCRU was a necessary element for complex formation. Upon 4 days of serum deprivation, this DNA-protein complex remained unchanged in HeLa cells, but the expression of TK mRNA was decreased. Furthermore, DNA methylation of the Hhal site of the CCRU sequence of the TK promoter greatly reduced the binding activity of nuclear proteins from different human tumor cell lines. On the basis of these data, we proposed a possible role for DNA methylation in the regulation of TK transcription during late G1/S phase progression of the cell cycle.", "contents": "Methylation-sensitive protein-DNA interaction at the cell cycle regulatory domain of human thymidine kinase promoter. We have investigated the DNA-protein complex formation in nuclear extracts of human cells using the sequence of cell-cycle regulatory unit (CCRU) of human thymidine kinase (TK) promoter. It appeared that a distinct DNA-protein complex was present in three human tumor cell lines and that the CCAAT box within the sequence of CCRU was a necessary element for complex formation. Upon 4 days of serum deprivation, this DNA-protein complex remained unchanged in HeLa cells, but the expression of TK mRNA was decreased. Furthermore, DNA methylation of the Hhal site of the CCRU sequence of the TK promoter greatly reduced the binding activity of nuclear proteins from different human tumor cell lines. On the basis of these data, we proposed a possible role for DNA methylation in the regulation of TK transcription during late G1/S phase progression of the cell cycle."} {"id": "PMID:1280427", "title": "Molecular cloning of hippocalcin, a novel calcium-binding protein of the recoverin family exclusively expressed in hippocampus.", "content": "We have isolated a cDNA clone encoding a novel calcium-binding protein of the recoverin family from rat brain cDNA library. This clone (PCB11) has 588 nucleotides in the open reading frame including the termination codon, 174 nucleotides of the 5' leader and 800 nucleotides of the 3' noncoding region. The complete amino acid sequence deduced from the cDNA is composed of 195 residues, has a calculated molecular mass of 22,574 Daltons, and contains three putative calcium-binding domains of the EF-hand structure. The deduced amino acid sequence has a striking sequence homology to those of the retinal recoverin family (recoverin, visinin, P26, 23kD protein, S-modulin) and the brain-derived recoverin family (P23k, 21-kDa CaBP and neurocalcin). Northern blot, in situ hybridization, immunoblot and immunohistochemical analyses revealed that the protein is exclusively expressed in pyramidal layer of the hippocampus. The protein was therefore designated hippocalcin.", "contents": "Molecular cloning of hippocalcin, a novel calcium-binding protein of the recoverin family exclusively expressed in hippocampus. We have isolated a cDNA clone encoding a novel calcium-binding protein of the recoverin family from rat brain cDNA library. This clone (PCB11) has 588 nucleotides in the open reading frame including the termination codon, 174 nucleotides of the 5' leader and 800 nucleotides of the 3' noncoding region. The complete amino acid sequence deduced from the cDNA is composed of 195 residues, has a calculated molecular mass of 22,574 Daltons, and contains three putative calcium-binding domains of the EF-hand structure. The deduced amino acid sequence has a striking sequence homology to those of the retinal recoverin family (recoverin, visinin, P26, 23kD protein, S-modulin) and the brain-derived recoverin family (P23k, 21-kDa CaBP and neurocalcin). Northern blot, in situ hybridization, immunoblot and immunohistochemical analyses revealed that the protein is exclusively expressed in pyramidal layer of the hippocampus. The protein was therefore designated hippocalcin."} {"id": "PMID:1280428", "title": "Inhibition of low pH evoked activation of airway sensory nerves by capsazepine, a novel capsaicin-receptor antagonist.", "content": "Low pH is a well known sensory irritant in pathological conditions such as inflammation. The mechanisms underlying this low pH effect were therefore studied in the guinea pig. Acid exposure caused marked nasal irritation via a specific subset of sensory nerves sensitive to capsaicin. Furthermore, acid caused bronchoconstriction via release of neuropeptides from capsaicin sensitive afferents. Interestingly, capsazepine, a recently developed competitive capsaicin receptor antagonist, selectively inhibited these responses to low pH. Ruthenium red, which blocks the cation channel associated with the capsaicin receptor, had effects similar to those of capsazepine. Therefore, acid irritation of the airway mucosa may involve capsaicin-receptor mechanisms and capsazepine represents a novel protective agent.", "contents": "Inhibition of low pH evoked activation of airway sensory nerves by capsazepine, a novel capsaicin-receptor antagonist. Low pH is a well known sensory irritant in pathological conditions such as inflammation. The mechanisms underlying this low pH effect were therefore studied in the guinea pig. Acid exposure caused marked nasal irritation via a specific subset of sensory nerves sensitive to capsaicin. Furthermore, acid caused bronchoconstriction via release of neuropeptides from capsaicin sensitive afferents. Interestingly, capsazepine, a recently developed competitive capsaicin receptor antagonist, selectively inhibited these responses to low pH. Ruthenium red, which blocks the cation channel associated with the capsaicin receptor, had effects similar to those of capsazepine. Therefore, acid irritation of the airway mucosa may involve capsaicin-receptor mechanisms and capsazepine represents a novel protective agent."} {"id": "PMID:1280429", "title": "Co-purification of 130 kD nitric oxide synthase and a 22 kD link protein from human neutrophils.", "content": "The synthesis of nitric oxide (NO) from L-arginine has been demonstrated in several cell types. Both constitutive and inducible forms of NO synthase have been described in different cells. We purified the constitutive form of NO synthase enzyme in human neutrophils using a two-column procedure. Crude 100,000g supernatant of human neutrophils was passed through a 2'-5'-ADP-agarose column followed by a DEAE-Bio-Gel A anion exchange column. NO synthase enzyme migrated as a single band (MW approximately 130,000) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Its activity was dependent upon nicotinamide adenine dinucleotide phosphate (NADPH) and (6R)-tetrahydro-L-biopterin (BH4). In addition, flavin adenine dinucleotide (FAD) was also found to be essential for its maximal activity. A second NADPH, FAD-dependent component (MW approximately 22kD) was also found consistently on the SDS-PAGE gel. These observations suggest co-regulation between NO synthase enzyme and this NADPH, FAD-dependent component, which may be associated with the superoxide radical generating system.", "contents": "Co-purification of 130 kD nitric oxide synthase and a 22 kD link protein from human neutrophils. The synthesis of nitric oxide (NO) from L-arginine has been demonstrated in several cell types. Both constitutive and inducible forms of NO synthase have been described in different cells. We purified the constitutive form of NO synthase enzyme in human neutrophils using a two-column procedure. Crude 100,000g supernatant of human neutrophils was passed through a 2'-5'-ADP-agarose column followed by a DEAE-Bio-Gel A anion exchange column. NO synthase enzyme migrated as a single band (MW approximately 130,000) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Its activity was dependent upon nicotinamide adenine dinucleotide phosphate (NADPH) and (6R)-tetrahydro-L-biopterin (BH4). In addition, flavin adenine dinucleotide (FAD) was also found to be essential for its maximal activity. A second NADPH, FAD-dependent component (MW approximately 22kD) was also found consistently on the SDS-PAGE gel. These observations suggest co-regulation between NO synthase enzyme and this NADPH, FAD-dependent component, which may be associated with the superoxide radical generating system."} {"id": "PMID:1280430", "title": "Detection of antibody to hepatitis C E2/NS1 protein in patients with type C hepatitis.", "content": "Putative E2/NS1 sequence of hepatitis C virus was expressed in E. coli as a fusion protein with maltose binding protein. Approximately 80 kDa protein was obtained containing 38 kDa E2/NS1 protein. The antibody to this protein was detectable in the same serum from which the sequence was amplified. It was also detectable in none of 7 acute hepatitis, in 2 of 12 chronic persistent hepatitis, in 3 of 25 chronic active hepatitis, and in 2 of 4 cirrhosis. It was detectable in none of 10 normal subjects. In 3 cases who were positive for the antibody before the interferon treatment, it became undetectable after the treatment. Thus, it seems that the antibody is not a neutralizing antibody and is related to active viral replication.", "contents": "Detection of antibody to hepatitis C E2/NS1 protein in patients with type C hepatitis. Putative E2/NS1 sequence of hepatitis C virus was expressed in E. coli as a fusion protein with maltose binding protein. Approximately 80 kDa protein was obtained containing 38 kDa E2/NS1 protein. The antibody to this protein was detectable in the same serum from which the sequence was amplified. It was also detectable in none of 7 acute hepatitis, in 2 of 12 chronic persistent hepatitis, in 3 of 25 chronic active hepatitis, and in 2 of 4 cirrhosis. It was detectable in none of 10 normal subjects. In 3 cases who were positive for the antibody before the interferon treatment, it became undetectable after the treatment. Thus, it seems that the antibody is not a neutralizing antibody and is related to active viral replication."} {"id": "PMID:1280431", "title": "Protein tyrosine phosphorylation as an indicator of 2,3,7,8-tetrachloro-p-dioxin exposure in vivo and in vitro.", "content": "A dose-dependent increase in tyrosine phosphorylation of five hepatic intracellular proteins with approximate molecular weights of 17, 21, 27, 29, and 34 kDa was seen 24 h after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to C57BL/6J female mice. The ED50 values for tyrosylphosphorylation of these five proteins, respectively, were 0.26, 0.21, 0.26, 0.31, and 0.38 micrograms TCDD/Kg. TCDD induction of 7-ethoxyresorufin O-deethylase activity (EROD) was characterized by an ED50 of 2.5 micrograms/Kg. An eighteen h exposure of a human lymphoblastoma cell line (X3) to TCDD increased tyrosylphosphorylation status of ten proteins with approximate molecular weights of 16, 17, 24, 26, 27, 32, 33, 34, 35, and 36 kDa in a dose-dependent manner. The EC50 values for these TCDD-dependent tyrosylphosphorylation ranged from 0.01 to 0.07 nM TCDD. EROD induction by TCDD in X3 cells exhibited an EC50 of 0.14 nM. These data indicate that TCDD alters intracellular protein tyrosine phosphorylation and these changes are more sensitive biological indicators of TCDD exposure than induction of EROD.", "contents": "Protein tyrosine phosphorylation as an indicator of 2,3,7,8-tetrachloro-p-dioxin exposure in vivo and in vitro. A dose-dependent increase in tyrosine phosphorylation of five hepatic intracellular proteins with approximate molecular weights of 17, 21, 27, 29, and 34 kDa was seen 24 h after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to C57BL/6J female mice. The ED50 values for tyrosylphosphorylation of these five proteins, respectively, were 0.26, 0.21, 0.26, 0.31, and 0.38 micrograms TCDD/Kg. TCDD induction of 7-ethoxyresorufin O-deethylase activity (EROD) was characterized by an ED50 of 2.5 micrograms/Kg. An eighteen h exposure of a human lymphoblastoma cell line (X3) to TCDD increased tyrosylphosphorylation status of ten proteins with approximate molecular weights of 16, 17, 24, 26, 27, 32, 33, 34, 35, and 36 kDa in a dose-dependent manner. The EC50 values for these TCDD-dependent tyrosylphosphorylation ranged from 0.01 to 0.07 nM TCDD. EROD induction by TCDD in X3 cells exhibited an EC50 of 0.14 nM. These data indicate that TCDD alters intracellular protein tyrosine phosphorylation and these changes are more sensitive biological indicators of TCDD exposure than induction of EROD."} {"id": "PMID:1280432", "title": "Mouse dopamine beta-hydroxylase: primary structure deduced from the cDNA sequence and exon/intron organization of the gene.", "content": "Genomic clones for mouse dopamine beta-hydroxylase (DBH) were isolated from two genomic libraries derived from DBA/2J and 129/SV mouse strains, by plaque hybridization with the human DBH cDNA probe. Subsequently, cDNA encoding mouse DBH was amplified with reverse transcription-polymerase chain reaction (RT-PCR) method using primers corresponding to 5'- and 3'-portions of the mouse DBH mRNA, subcloned into a plasmid vector, and subjected to nucleotide sequence analysis. The clone encoded a protein of 621 amino acids with a calculated molecular mass of 70,186 daltons. The predicted amino acid sequence of mouse DBH showed 87%, 80% and 79% identities with the rat, bovine and human enzymes, respectively. Several potential amino acid sequences that are involved in the posttranslational modification and catalytic function of DBH were identified in mouse DBH protein. Nucleotide sequence analysis of the overlapping genomic clones showed that the mouse DBH gene was composed of 12 exons about 17 kb in length. Typical TATA and CCAAT boxes were observed in the 5'-upstream region of the gene. Northern blot analysis of adrenal gland RNA detected a single size species of the mouse DBH mRNA.", "contents": "Mouse dopamine beta-hydroxylase: primary structure deduced from the cDNA sequence and exon/intron organization of the gene. Genomic clones for mouse dopamine beta-hydroxylase (DBH) were isolated from two genomic libraries derived from DBA/2J and 129/SV mouse strains, by plaque hybridization with the human DBH cDNA probe. Subsequently, cDNA encoding mouse DBH was amplified with reverse transcription-polymerase chain reaction (RT-PCR) method using primers corresponding to 5'- and 3'-portions of the mouse DBH mRNA, subcloned into a plasmid vector, and subjected to nucleotide sequence analysis. The clone encoded a protein of 621 amino acids with a calculated molecular mass of 70,186 daltons. The predicted amino acid sequence of mouse DBH showed 87%, 80% and 79% identities with the rat, bovine and human enzymes, respectively. Several potential amino acid sequences that are involved in the posttranslational modification and catalytic function of DBH were identified in mouse DBH protein. Nucleotide sequence analysis of the overlapping genomic clones showed that the mouse DBH gene was composed of 12 exons about 17 kb in length. Typical TATA and CCAAT boxes were observed in the 5'-upstream region of the gene. Northern blot analysis of adrenal gland RNA detected a single size species of the mouse DBH mRNA."} {"id": "PMID:1280433", "title": "Platelet-derived growth factor gene expression in cultured human retinal pigment epithelial cells.", "content": "Gene expression of platelet-derived growth factor (PDGF) and its receptors in cultured human retinal pigment epithelial (RPE) cells was studied by using semiquantitative polymerase chain reaction. The RPE cells were found to express PDGF A- and B-chain genes as well as alpha- and beta-receptor genes with dominant expression of B-chain and beta-receptor isoforms. Phorbol myristate acetate (PMA) and thrombin increased the expression of PDGF B-chain gene to 19.8 +/- 1.75 and 15.9 +/- 1.84 fold (n = 3) of the control without affecting beta-receptor gene expression. PDGF produced by the RPE cells may play an important role in the pathogenesis of some ocular proliferative diseases.", "contents": "Platelet-derived growth factor gene expression in cultured human retinal pigment epithelial cells. Gene expression of platelet-derived growth factor (PDGF) and its receptors in cultured human retinal pigment epithelial (RPE) cells was studied by using semiquantitative polymerase chain reaction. The RPE cells were found to express PDGF A- and B-chain genes as well as alpha- and beta-receptor genes with dominant expression of B-chain and beta-receptor isoforms. Phorbol myristate acetate (PMA) and thrombin increased the expression of PDGF B-chain gene to 19.8 +/- 1.75 and 15.9 +/- 1.84 fold (n = 3) of the control without affecting beta-receptor gene expression. PDGF produced by the RPE cells may play an important role in the pathogenesis of some ocular proliferative diseases."} {"id": "PMID:1280434", "title": "Inactivation of substance P by granulation tissue-derived gelatinase.", "content": "An active gelatinase has been purified from the conditioned medium of granulation tissue culture formed by carrageenin injection in rats. The purified gelatinase gave a single band corresponding to a M(r) of 57 kDa on both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and SDS-gelatin PAGE. The granulation tissue-derived gelatinase selectively cleaved the Gln6-Phe7 bond of substance P (SP) with a Km of 0.17 mM and a Vmax of 0.027 nmol SP7-11/min/micrograms protein, resulting in the generation of biologically inactive fragments, SP1-6 and SP7-11. Our data suggest that the gelatinase produced by granulation tissue participates in the inactivation of SP in the inflammatory site.", "contents": "Inactivation of substance P by granulation tissue-derived gelatinase. An active gelatinase has been purified from the conditioned medium of granulation tissue culture formed by carrageenin injection in rats. The purified gelatinase gave a single band corresponding to a M(r) of 57 kDa on both sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and SDS-gelatin PAGE. The granulation tissue-derived gelatinase selectively cleaved the Gln6-Phe7 bond of substance P (SP) with a Km of 0.17 mM and a Vmax of 0.027 nmol SP7-11/min/micrograms protein, resulting in the generation of biologically inactive fragments, SP1-6 and SP7-11. Our data suggest that the gelatinase produced by granulation tissue participates in the inactivation of SP in the inflammatory site."} {"id": "PMID:1280435", "title": "Inhibition of nicotinic acetylcholine receptor-mediated secretion and synthesis of catecholamines by sea urchin toxin in cultured bovine adrenal medullary cells.", "content": "We previously reported the partial purification and characterization of a toxic substance (sea urchin toxin) isolated from the pedicellariae of the sea urchin Toxopneustes pileolus (Nakagawa and Kimura, Jpn J Pharmacol 32: 966-968, 1982). In the present study, we examined the effect of sea urchin toxin on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Sea urchin toxin inhibited the secretion of catecholamines stimulated by carbachol and nicotine but not by veratridine or a high concentration of K+. The toxin inhibited the carbachol-evoked influx of 22Na+ and 45Ca2+ at concentrations similar to those for catecholamine secretion. The inhibition of catecholamine secretion by sea urchin toxin was not overcome by increasing the concentration of carbachol. Preincubation of cells with the toxin caused a time-dependent inhibition in the secretion stimulated by carbachol even when the toxin was removed from the incubation medium. The toxin suppressed catecholamine synthesis and tyrosine hydroxylase activity in carbachol-stimulated cells. In addition, sea urchin toxin inhibited [3H]phencyclidine binding to adrenal medullary cells whereas it did not alter cyclic GMP accumulation caused by muscarine. Further purified fractions from sea urchin toxin by concanavalin A affinity column chromatography also inhibited carbachol-evoked secretion of catecholamines. These results suggest that sea urchin toxin inhibits carbachol-enhanced secretion and synthesis of catecholamines by suppression of nicotinic acetylcholine receptor-mediated Na+ influx and subsequent Ca2+ influx in cultured adrenal medullary cells.", "contents": "Inhibition of nicotinic acetylcholine receptor-mediated secretion and synthesis of catecholamines by sea urchin toxin in cultured bovine adrenal medullary cells. We previously reported the partial purification and characterization of a toxic substance (sea urchin toxin) isolated from the pedicellariae of the sea urchin Toxopneustes pileolus (Nakagawa and Kimura, Jpn J Pharmacol 32: 966-968, 1982). In the present study, we examined the effect of sea urchin toxin on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Sea urchin toxin inhibited the secretion of catecholamines stimulated by carbachol and nicotine but not by veratridine or a high concentration of K+. The toxin inhibited the carbachol-evoked influx of 22Na+ and 45Ca2+ at concentrations similar to those for catecholamine secretion. The inhibition of catecholamine secretion by sea urchin toxin was not overcome by increasing the concentration of carbachol. Preincubation of cells with the toxin caused a time-dependent inhibition in the secretion stimulated by carbachol even when the toxin was removed from the incubation medium. The toxin suppressed catecholamine synthesis and tyrosine hydroxylase activity in carbachol-stimulated cells. In addition, sea urchin toxin inhibited [3H]phencyclidine binding to adrenal medullary cells whereas it did not alter cyclic GMP accumulation caused by muscarine. Further purified fractions from sea urchin toxin by concanavalin A affinity column chromatography also inhibited carbachol-evoked secretion of catecholamines. These results suggest that sea urchin toxin inhibits carbachol-enhanced secretion and synthesis of catecholamines by suppression of nicotinic acetylcholine receptor-mediated Na+ influx and subsequent Ca2+ influx in cultured adrenal medullary cells."} {"id": "PMID:1280436", "title": "Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 94-100 (antigenic site 3) of myoglobin.", "content": "Amino acid substitutions outside protein antigenic sites are very frequently assumed to exert no effect on binding to antiprotein antibodies, especially if these are monoclonal antibodies (mAbs). In fact, a very popular method for localization of residues in protein antigenic sites is based on the interpretation that whenever a replacement causes a change in binding to antibody, then that residue will be located in the antigenic site. To test this assumption, mAbs of predetermined specificity were prepared by immunization with a free (i.e., without coupling to any carrier) synthetic peptide representing region 94-100 of sperm whale myoglobin (Mb). The cross-reactivities and relative affinities of three mAbs with eight Mb variants were studied. Five Mb variants which had no substitutions within the boundaries of the designed antigenic site exhibited remarkable, and in two cases almost complete, loss in cross-reactivity relative to the reference antigen, sperm whale Mb. Two myoglobins, each of which had one substitution within region 94-100, showed little or no reactivity with the three mAbs. It is concluded that substitutions outside an antigenic site can exert drastic effects on the reactivity of a protein with mAbs against the site and that caution should be exercised in interpreting cross-reactivity data of proteins to implicate residues directly in an antigenic site.", "contents": "Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 94-100 (antigenic site 3) of myoglobin. Amino acid substitutions outside protein antigenic sites are very frequently assumed to exert no effect on binding to antiprotein antibodies, especially if these are monoclonal antibodies (mAbs). In fact, a very popular method for localization of residues in protein antigenic sites is based on the interpretation that whenever a replacement causes a change in binding to antibody, then that residue will be located in the antigenic site. To test this assumption, mAbs of predetermined specificity were prepared by immunization with a free (i.e., without coupling to any carrier) synthetic peptide representing region 94-100 of sperm whale myoglobin (Mb). The cross-reactivities and relative affinities of three mAbs with eight Mb variants were studied. Five Mb variants which had no substitutions within the boundaries of the designed antigenic site exhibited remarkable, and in two cases almost complete, loss in cross-reactivity relative to the reference antigen, sperm whale Mb. Two myoglobins, each of which had one substitution within region 94-100, showed little or no reactivity with the three mAbs. It is concluded that substitutions outside an antigenic site can exert drastic effects on the reactivity of a protein with mAbs against the site and that caution should be exercised in interpreting cross-reactivity data of proteins to implicate residues directly in an antigenic site."} {"id": "PMID:1280437", "title": "Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 15-22 (antigenic site 1) of myoglobin.", "content": "Monoclonal antibodies (mAbs) of predetermined specificity were prepared by immunizing with a free (i.e., not conjugated to any carrier) synthetic peptide representing region 15-22 (site 1) of sperm whale myoglobin (SpMb). The cross-reactions of Mb variants with three mAbs were studied in order to determine whether such interactions are influenced by substitutions outside the site. Finback whale Mb, which has no substitutions within region 15-22, showed lower cross-reactivity and relative binding affinity than the reference antigen, SpMb. Bottle-nose Atlantic dolphin myoglobin (BdMb) and badger myoglobin (BgMb), although they have identical substitutions within region 15-22 (Ala-15 to Gly and Val-21 to Leu), showed very different binding properties. The cross-reaction of BdMb was quite comparable to that of SpMb, while that of BgMb was much lower. Since the two proteins have identical structures in regions 15-22, the differences in their cross-reactivities are readily attributed to the effects of substitutions outside this region. Another pair of myoglobins, horse myoglobins (HsMb) and chicken myoglobin (ChMb), also have two identical substitutions (Ala-15 to Gly and Val-21 to Ile) within region 15-22, but possessed different cross-reactivity. The results indicate that the reaction of mAbs, whose specificity is precisely known and predetermined by the immunizing free peptide, can be markedly affected by substitutions outside the indicated binding region on the protein.", "contents": "Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 15-22 (antigenic site 1) of myoglobin. Monoclonal antibodies (mAbs) of predetermined specificity were prepared by immunizing with a free (i.e., not conjugated to any carrier) synthetic peptide representing region 15-22 (site 1) of sperm whale myoglobin (SpMb). The cross-reactions of Mb variants with three mAbs were studied in order to determine whether such interactions are influenced by substitutions outside the site. Finback whale Mb, which has no substitutions within region 15-22, showed lower cross-reactivity and relative binding affinity than the reference antigen, SpMb. Bottle-nose Atlantic dolphin myoglobin (BdMb) and badger myoglobin (BgMb), although they have identical substitutions within region 15-22 (Ala-15 to Gly and Val-21 to Leu), showed very different binding properties. The cross-reaction of BdMb was quite comparable to that of SpMb, while that of BgMb was much lower. Since the two proteins have identical structures in regions 15-22, the differences in their cross-reactivities are readily attributed to the effects of substitutions outside this region. Another pair of myoglobins, horse myoglobins (HsMb) and chicken myoglobin (ChMb), also have two identical substitutions (Ala-15 to Gly and Val-21 to Ile) within region 15-22, but possessed different cross-reactivity. The results indicate that the reaction of mAbs, whose specificity is precisely known and predetermined by the immunizing free peptide, can be markedly affected by substitutions outside the indicated binding region on the protein."} {"id": "PMID:1280438", "title": "Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 56-62 (antigenic site 2) of myoglobin.", "content": "This work was carried out in order to study the effects of substitutions outside antigenic site 2 of sperm whale myoglobin (SpMb) on the reactivity of protein variants with antisite 2 monoclonal antibodies (mAbs). A synthetic peptide corresponding to region 56-62 (site 2) of SpMb was used as an immunogen in mice in its free form (i.e., without coupling to any carrier) to prepare a panel of mAbs whose predetermined specificity is directed, by design, against this region. The binding of three of these mAbs to eight Mbs from different species was studied. Myoglobins of Pacific common dolphin, finback whale, and horse, which have no substitutions within region 56-62 relative to SpMb, showed remarkable differences in their cross-reactivities and relative affinities with each of the mAbs. Myoglobins of badger, chicken, and dog, although they have an identical substitution within the site (Ala-57 to Gly), exhibited cross-reactivities with a given mAb that were affected differently. Echidna Mb, which has one replacement (Glu-59 to Ala) within region 56-62, displayed greatly reduced cross-reactivities and relative binding affinities. The results, especially those from Mbs that have no substitutions within the boundaries of site 2, clearly indicate that substitutions outside site 2 of Mb can exert drastic effects on the binding of the Mb variants with mAbs whose specificity was predesigned to be against the site. These indirect effects and their impact on site reactivity will completely explain previous findings on cross-reactivities of Mb variants with mAbs of unknown specificity and will rule out the postulations of discontinuous sites in Mb, which were based on the assumption that every substitution affecting reactivity is directly involved in binding to antibody.", "contents": "Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 56-62 (antigenic site 2) of myoglobin. This work was carried out in order to study the effects of substitutions outside antigenic site 2 of sperm whale myoglobin (SpMb) on the reactivity of protein variants with antisite 2 monoclonal antibodies (mAbs). A synthetic peptide corresponding to region 56-62 (site 2) of SpMb was used as an immunogen in mice in its free form (i.e., without coupling to any carrier) to prepare a panel of mAbs whose predetermined specificity is directed, by design, against this region. The binding of three of these mAbs to eight Mbs from different species was studied. Myoglobins of Pacific common dolphin, finback whale, and horse, which have no substitutions within region 56-62 relative to SpMb, showed remarkable differences in their cross-reactivities and relative affinities with each of the mAbs. Myoglobins of badger, chicken, and dog, although they have an identical substitution within the site (Ala-57 to Gly), exhibited cross-reactivities with a given mAb that were affected differently. Echidna Mb, which has one replacement (Glu-59 to Ala) within region 56-62, displayed greatly reduced cross-reactivities and relative binding affinities. The results, especially those from Mbs that have no substitutions within the boundaries of site 2, clearly indicate that substitutions outside site 2 of Mb can exert drastic effects on the binding of the Mb variants with mAbs whose specificity was predesigned to be against the site. These indirect effects and their impact on site reactivity will completely explain previous findings on cross-reactivities of Mb variants with mAbs of unknown specificity and will rule out the postulations of discontinuous sites in Mb, which were based on the assumption that every substitution affecting reactivity is directly involved in binding to antibody."} {"id": "PMID:1280439", "title": "Covalent attachment of ribonucleic acids to proteins.", "content": "As a prerequisite for the synthesis of affinity labels, we describe methods to couple histones to ribonucleic acids. For the synthesis of these covalent hybrid molecules, we used a population of histones H1, H2A, H2B, H3, and H4 from calf thymus and polyadenylic acid with an average chain length of up to 260-280 bases, representing the size of poly(A)-tails from mature mRNAs. Three methods were investigated. (a) Poly(A) containing an 8-N3-A residue was cross-linked to histones by ultraviolet irradiation. (b) The 3'-end of the polynucleotide was connected to a mononucleotide containing an aliphatic amino group, and the resulting poly(A)-derivative was coupled to histones via derivation with a bromoacetyl group. (c) The 3'-end of the polynucleotide was oxidized with sodium periodate and bound covalently to an amino group of the polypeptide. To demonstrate the RNA content of the hybrid molecule, the poly(A) was removed with RNase T2.", "contents": "Covalent attachment of ribonucleic acids to proteins. As a prerequisite for the synthesis of affinity labels, we describe methods to couple histones to ribonucleic acids. For the synthesis of these covalent hybrid molecules, we used a population of histones H1, H2A, H2B, H3, and H4 from calf thymus and polyadenylic acid with an average chain length of up to 260-280 bases, representing the size of poly(A)-tails from mature mRNAs. Three methods were investigated. (a) Poly(A) containing an 8-N3-A residue was cross-linked to histones by ultraviolet irradiation. (b) The 3'-end of the polynucleotide was connected to a mononucleotide containing an aliphatic amino group, and the resulting poly(A)-derivative was coupled to histones via derivation with a bromoacetyl group. (c) The 3'-end of the polynucleotide was oxidized with sodium periodate and bound covalently to an amino group of the polypeptide. To demonstrate the RNA content of the hybrid molecule, the poly(A) was removed with RNase T2."} {"id": "PMID:1280442", "title": "Effect of alcohol on urinary and blood dolichols.", "content": "Alcohol appears to affect dolichol metabolism, as both serum and urinary dolichol concentrations were found to be significantly higher in alcoholics than in social drinkers. Furthermore, acute heavy drinking (5.5 g alcohol/kg body weight during 42 h) increased urinary dolichol excretion significantly, whereas moderate drinking (60 g/day for 10 days) had no effect. Increased urinary dolichol concentrations in alcoholics returned rapidly to normal with a half-life decay of 3 days, whereas increased serum dolichol concentrations did not change during a 7-day observation period. The mechanism behind alcohol-induced alterations in dolichol metabolism remains unclear, but based on our results, it seems likely that serum and urinary dolichols are regulated independently from each other.", "contents": "Effect of alcohol on urinary and blood dolichols. Alcohol appears to affect dolichol metabolism, as both serum and urinary dolichol concentrations were found to be significantly higher in alcoholics than in social drinkers. Furthermore, acute heavy drinking (5.5 g alcohol/kg body weight during 42 h) increased urinary dolichol excretion significantly, whereas moderate drinking (60 g/day for 10 days) had no effect. Increased urinary dolichol concentrations in alcoholics returned rapidly to normal with a half-life decay of 3 days, whereas increased serum dolichol concentrations did not change during a 7-day observation period. The mechanism behind alcohol-induced alterations in dolichol metabolism remains unclear, but based on our results, it seems likely that serum and urinary dolichols are regulated independently from each other."} {"id": "PMID:1280443", "title": "Development of T7 phage and T7 phage containing apurinic sites in an exonuclease III, endonuclease IV double mutant of Escherichia coli.", "content": "The development of bacteriophage T7 was examined in an Escherichia coli double mutant defective for the two major apurinic, apyrimidinic endonucleases (exonuclease III and endonuclease IV, xth nfo). In cells infected with phages containing apurinic sites, the defect in repair enzymes led to a decrease of phage survival and a total absence of bacterial DNA degradation and of phage DNA synthesis. These results directly demonstrate the toxic action of apurinic sites on bacteriophage T7 at the intracellular level and its alleviation by DNA repair. In addition, untreated T7 phage unexpectedly displayed reduced plating efficiency and decreased DNA synthesis in the xth nfo double mutant.", "contents": "Development of T7 phage and T7 phage containing apurinic sites in an exonuclease III, endonuclease IV double mutant of Escherichia coli. The development of bacteriophage T7 was examined in an Escherichia coli double mutant defective for the two major apurinic, apyrimidinic endonucleases (exonuclease III and endonuclease IV, xth nfo). In cells infected with phages containing apurinic sites, the defect in repair enzymes led to a decrease of phage survival and a total absence of bacterial DNA degradation and of phage DNA synthesis. These results directly demonstrate the toxic action of apurinic sites on bacteriophage T7 at the intracellular level and its alleviation by DNA repair. In addition, untreated T7 phage unexpectedly displayed reduced plating efficiency and decreased DNA synthesis in the xth nfo double mutant."} {"id": "PMID:1280444", "title": "Therapeutic applications of oligonucleotides.", "content": "This review focuses strictly on the pharmacodynamic considerations of the use of oligonucleotides designed to interact with nucleic acids as therapeutics. The objectives are to place oligonucleotide therapeutics in the context of modern drug discovery and development and to summarize recent progress.", "contents": "Therapeutic applications of oligonucleotides. This review focuses strictly on the pharmacodynamic considerations of the use of oligonucleotides designed to interact with nucleic acids as therapeutics. The objectives are to place oligonucleotide therapeutics in the context of modern drug discovery and development and to summarize recent progress."} {"id": "PMID:1280445", "title": "The internal representation of arithmetical word problem sentences: frontal and posterior-injured patients compared.", "content": "Patients with frontal and left posterior brain lesions have severe difficulties in arithmetical word problem solving. In the present study the origin of these difficulties is investigated from an information-processing perspective. Following this perspective the first stage in word problem solving consists of a translation of individual sentences to an internal representation. This translation process is examined in 30 frontal patients, 10 left posterior-injured patients, and 10 healthy controls with a recognition and a sentence-picture matching task. In addition, the relationship between sentence representation and arithmetical word problem solving is studied. The results suggest that error rates in the translation of different types of arithmetical word problem propositions differ substantially in our three groups. A relationship between translation skills and arithmetical word problem solving ability is also found.", "contents": "The internal representation of arithmetical word problem sentences: frontal and posterior-injured patients compared. Patients with frontal and left posterior brain lesions have severe difficulties in arithmetical word problem solving. In the present study the origin of these difficulties is investigated from an information-processing perspective. Following this perspective the first stage in word problem solving consists of a translation of individual sentences to an internal representation. This translation process is examined in 30 frontal patients, 10 left posterior-injured patients, and 10 healthy controls with a recognition and a sentence-picture matching task. In addition, the relationship between sentence representation and arithmetical word problem solving is studied. The results suggest that error rates in the translation of different types of arithmetical word problem propositions differ substantially in our three groups. A relationship between translation skills and arithmetical word problem solving ability is also found."} {"id": "PMID:1280447", "title": "Treatment of subfoveal choroidal neovascular membranes with systemic interferon-alpha 2a.", "content": "Systemic interferon-alpha has recently been reported to be useful in the treatment of choroidal neovascular membranes (CNVM) in age-related macular degeneration. To further investigate its effect we treated eight patients with subfoveal choroidal neovascular membranes of various aetiologies including idiopathic, age-related macular degeneration and myopic chorioretinal degeneration. Only one of the eight patients responded with an angiographically demonstrated decrease in the size of the CNVM; this was in a patient from the idiopathic group. Considerable side-effects were reported with marked lethargy and malaise limiting compliance with some patients. Although this is an initial report with limited patient numbers and follow-up, it does suggest a role for interferon-alpha in patients with idiopathic neovascular membranes where the retina is otherwise normal, but raises some doubt as to its efficacy in the treatment of age-related macular degeneration.", "contents": "Treatment of subfoveal choroidal neovascular membranes with systemic interferon-alpha 2a. Systemic interferon-alpha has recently been reported to be useful in the treatment of choroidal neovascular membranes (CNVM) in age-related macular degeneration. To further investigate its effect we treated eight patients with subfoveal choroidal neovascular membranes of various aetiologies including idiopathic, age-related macular degeneration and myopic chorioretinal degeneration. Only one of the eight patients responded with an angiographically demonstrated decrease in the size of the CNVM; this was in a patient from the idiopathic group. Considerable side-effects were reported with marked lethargy and malaise limiting compliance with some patients. Although this is an initial report with limited patient numbers and follow-up, it does suggest a role for interferon-alpha in patients with idiopathic neovascular membranes where the retina is otherwise normal, but raises some doubt as to its efficacy in the treatment of age-related macular degeneration."} {"id": "PMID:1280448", "title": "Corneal storage at 4 degrees Celsius in a chondroitin sulphate and dextran containing medium.", "content": "Corneas were stored at 4 degrees C in a chondroitin sulphate and dextran containing medium from one to ten days. The viability of the corneal endothelium was assessed after storage with the vital stain, trypan blue.", "contents": "Corneal storage at 4 degrees Celsius in a chondroitin sulphate and dextran containing medium. Corneas were stored at 4 degrees C in a chondroitin sulphate and dextran containing medium from one to ten days. The viability of the corneal endothelium was assessed after storage with the vital stain, trypan blue."} {"id": "PMID:1280449", "title": "Identification of a mouse B-type cyclin which exhibits developmentally regulated expression in the germ line.", "content": "To begin to examine the function of cyclins in mammalian germ cells, we have screened an adult mouse testis cDNA library for the presence of B-type cyclins. We have isolated cDNAs that encode a murine B-type cyclin, which has been designated cycB1. cycB1 was shown to be expressed in several adult tissues and in the midgestation mouse embryo. In the adult tissues, the highest levels of cycB1 transcripts were seen in the testis and ovary, which contain germ cells at various stages of differentiation. The major transcripts corresponding to cycB1 are 1.7 and 2.5 kb, with the 1.7 kb species being the predominant testicular transcript and the 2.5 kb species more abundant in the ovary. Examination of cDNAs corresponding to the 2.5 kb and 1.7 kb mRNAs revealed that these transcripts encode identical proteins, differing only in the polyadenylation signal used and therefore in the length of their 3' untranslated regions. Northern blot and in situ hybridization analyses revealed that the predominant sites of cycB1 expression in the testis and ovary were in the germinal compartment, particularly in early round spermatids in the testis and growing oocytes in the ovary. Thus cycB1 is expressed in both meiotic and postmeiotic cells. This pattern of cycB1 expression further suggests that cycB1 may have different functions in the two cell types, only one of which correlates with progression of the cell cycle.", "contents": "Identification of a mouse B-type cyclin which exhibits developmentally regulated expression in the germ line. To begin to examine the function of cyclins in mammalian germ cells, we have screened an adult mouse testis cDNA library for the presence of B-type cyclins. We have isolated cDNAs that encode a murine B-type cyclin, which has been designated cycB1. cycB1 was shown to be expressed in several adult tissues and in the midgestation mouse embryo. In the adult tissues, the highest levels of cycB1 transcripts were seen in the testis and ovary, which contain germ cells at various stages of differentiation. The major transcripts corresponding to cycB1 are 1.7 and 2.5 kb, with the 1.7 kb species being the predominant testicular transcript and the 2.5 kb species more abundant in the ovary. Examination of cDNAs corresponding to the 2.5 kb and 1.7 kb mRNAs revealed that these transcripts encode identical proteins, differing only in the polyadenylation signal used and therefore in the length of their 3' untranslated regions. Northern blot and in situ hybridization analyses revealed that the predominant sites of cycB1 expression in the testis and ovary were in the germinal compartment, particularly in early round spermatids in the testis and growing oocytes in the ovary. Thus cycB1 is expressed in both meiotic and postmeiotic cells. This pattern of cycB1 expression further suggests that cycB1 may have different functions in the two cell types, only one of which correlates with progression of the cell cycle."} {"id": "PMID:1280450", "title": "Role of tyrosine kinases in IgE-mediated signal transduction in human lung mast cells and basophils.", "content": "Recent evidence suggests that tyrosine kinases play an important role in signal transduction mechanisms utilized by a range of different agonists in many cell types. We have investigated the effects of four different inhibitors of tyrosine kinases on IgE-dependent histamine release from human lung mast cells and basophils. Genistein inhibited the anti-IgE-induced histamine release from human basophils (at 10 microM genistein, inhibition = 55 +/- 5%, n = 17, P < 0.005) with an IC50 of 8 microM, but was much less effective in the human lung mast cell (at 10 microM, inhibition = 18 +/- 6%, n = 11, P < 0.05). Two inactive analogs of genistein, genistin and diadzein, failed to affect anti-IgE-induced histamine release significantly in either mast cells or basophils. A second inhibitor of tyrosine kinases, tyrphostin 25, inhibited IgE-dependent release from basophils (at 10 microM, inhibition = 25 +/- 7%, n = 6, P < 0.05) though it was less effective than genistein and failed to affect IgE-induced histamine release from human lung mast cells (at 10 microM, inhibition = 22 +/- 16%, n = 5, P = NS). In contrast, methyl 2,5 dihydroxycinnamate (MDC) failed to inhibit anti-IgE-dependent histamine release in human basophils (at 10 microM, inhibition = 3 +/- 3%, n = 5, P = NS) but proved to be an effective inhibitor of anti-IgE-induced degranulation in human lung mast cells (at 10 microM, inhibition = 53 +/- 16%, n = 5, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Role of tyrosine kinases in IgE-mediated signal transduction in human lung mast cells and basophils. Recent evidence suggests that tyrosine kinases play an important role in signal transduction mechanisms utilized by a range of different agonists in many cell types. We have investigated the effects of four different inhibitors of tyrosine kinases on IgE-dependent histamine release from human lung mast cells and basophils. Genistein inhibited the anti-IgE-induced histamine release from human basophils (at 10 microM genistein, inhibition = 55 +/- 5%, n = 17, P < 0.005) with an IC50 of 8 microM, but was much less effective in the human lung mast cell (at 10 microM, inhibition = 18 +/- 6%, n = 11, P < 0.05). Two inactive analogs of genistein, genistin and diadzein, failed to affect anti-IgE-induced histamine release significantly in either mast cells or basophils. A second inhibitor of tyrosine kinases, tyrphostin 25, inhibited IgE-dependent release from basophils (at 10 microM, inhibition = 25 +/- 7%, n = 6, P < 0.05) though it was less effective than genistein and failed to affect IgE-induced histamine release from human lung mast cells (at 10 microM, inhibition = 22 +/- 16%, n = 5, P = NS). In contrast, methyl 2,5 dihydroxycinnamate (MDC) failed to inhibit anti-IgE-dependent histamine release in human basophils (at 10 microM, inhibition = 3 +/- 3%, n = 5, P = NS) but proved to be an effective inhibitor of anti-IgE-induced degranulation in human lung mast cells (at 10 microM, inhibition = 53 +/- 16%, n = 5, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280451", "title": "Murine strain differences in acute lung injury and activation of poly(ADP-ribose) polymerase by in vitro exposure of lung slices to bleomycin.", "content": "The DNA-cleaving, antitumor antibiotic bleomycin (BLM) causes pulmonary fibrosis, but the essential early events initiating the fibrotic state have not been well characterized. Thus, we have directly examined BLM-mediated pulmonary cell injury by monitoring lactate dehydrogenase (LDH) release and nuclear poly(ADP-ribose) polymerase (PAP) activity, which is stimulated by DNA breakage, using lung slices isolated from BLM-sensitive (C57B1/6) and BLM-resistant (BALB/c) mice. Lung slices were incubated continuously with or without the PAP inhibitor, 3-aminobenzamide (3-AB), and exposed to BLM for 45 min. LDH release from C57B1/6 lung slices increased 2-fold by 8.5 h after treatment with BLM. In contrast, BLM failed to enhance cumulative LDH release by BALB/c mouse lung slices. Co-incubation of C57B1/6 lung slices with 3-AB prevented BLM-induced LDH release. Nuclear PAP was activated 3- to 4-fold 1.25 h after exposure of C57B1/6 lung slices to BLM but returned to control levels by 3.75 h. Nuclear PAP was only marginally affected at these times in BALB/c lung slices. Co-incubation of C57B1/6 slices with 3-AB prevented the early increases in PAP activity. These results demonstrate that murine strain sensitivity to acute cell injury and early PAP activation by BLM in lung slices parallels the in vivo sensitivity of lungs. In addition, 3-AB suppresses PAP activation and acute cell injury in lung slices. Differential activation of PAP appears to govern murine strain variation in response to BLM and is consistent with the hypothesis that activation of PAP participates in acute pneumocyte injury, initiating the process of BLM-induced fibrosis.", "contents": "Murine strain differences in acute lung injury and activation of poly(ADP-ribose) polymerase by in vitro exposure of lung slices to bleomycin. The DNA-cleaving, antitumor antibiotic bleomycin (BLM) causes pulmonary fibrosis, but the essential early events initiating the fibrotic state have not been well characterized. Thus, we have directly examined BLM-mediated pulmonary cell injury by monitoring lactate dehydrogenase (LDH) release and nuclear poly(ADP-ribose) polymerase (PAP) activity, which is stimulated by DNA breakage, using lung slices isolated from BLM-sensitive (C57B1/6) and BLM-resistant (BALB/c) mice. Lung slices were incubated continuously with or without the PAP inhibitor, 3-aminobenzamide (3-AB), and exposed to BLM for 45 min. LDH release from C57B1/6 lung slices increased 2-fold by 8.5 h after treatment with BLM. In contrast, BLM failed to enhance cumulative LDH release by BALB/c mouse lung slices. Co-incubation of C57B1/6 lung slices with 3-AB prevented BLM-induced LDH release. Nuclear PAP was activated 3- to 4-fold 1.25 h after exposure of C57B1/6 lung slices to BLM but returned to control levels by 3.75 h. Nuclear PAP was only marginally affected at these times in BALB/c lung slices. Co-incubation of C57B1/6 slices with 3-AB prevented the early increases in PAP activity. These results demonstrate that murine strain sensitivity to acute cell injury and early PAP activation by BLM in lung slices parallels the in vivo sensitivity of lungs. In addition, 3-AB suppresses PAP activation and acute cell injury in lung slices. Differential activation of PAP appears to govern murine strain variation in response to BLM and is consistent with the hypothesis that activation of PAP participates in acute pneumocyte injury, initiating the process of BLM-induced fibrosis."} {"id": "PMID:1280452", "title": "Does ND-YAG laser extend the indications for resection of pulmonary metastases?", "content": "Surgery forms part of a combined oncological concept in the management of pulmonary metastases. The following questions are relevant for its role: Does survival depend on the type of primary tumor? Are there any prognostic factors? What are the limits on radical resection? We analyzed retrospectively 657 patients who had undergone 759 resections of pulmonary metastases between 1973 and 1990. After conducting in vitro and in vivo experiments with the non-contact neodymium aluminum garnet (Nd-YAG) laser with a generating and delivery power of 10-120 W at the site of operation for 0.1-9.9 s, we have treated 65 patients by laser resection and/or vaporization since January 1990. Our preferred surgical approach was median or transverse thoracotomy. The 5-year survival of all resected patients was 30%, ranging from 21% (soft tissue sarcoma) to 60% (testicular carcinoma). Statistically significant differences in prognosis were seen related to the type of primary tumor, the disease-free interval, the caval or portal type of metastatic spread, the number of metastases and the potential degree of radical resection. The potential degree of conventional radical resections (wedge, anatomical sub-/segmental) was negatively influenced by the number of metastases (n > 9: 79% \"radical\" surgery = 38% 5-year survival). Laser treatment allowed parenchyma-preserving resection in cases of metastases of more than 0.5 cm in diameter, and vaporization in smaller ones. Resection with the intention of achieving complete remission was possible in up to 72 unilateral metastases. The complication rate was comparable to conventional resections.", "contents": "Does ND-YAG laser extend the indications for resection of pulmonary metastases? Surgery forms part of a combined oncological concept in the management of pulmonary metastases. The following questions are relevant for its role: Does survival depend on the type of primary tumor? Are there any prognostic factors? What are the limits on radical resection? We analyzed retrospectively 657 patients who had undergone 759 resections of pulmonary metastases between 1973 and 1990. After conducting in vitro and in vivo experiments with the non-contact neodymium aluminum garnet (Nd-YAG) laser with a generating and delivery power of 10-120 W at the site of operation for 0.1-9.9 s, we have treated 65 patients by laser resection and/or vaporization since January 1990. Our preferred surgical approach was median or transverse thoracotomy. The 5-year survival of all resected patients was 30%, ranging from 21% (soft tissue sarcoma) to 60% (testicular carcinoma). Statistically significant differences in prognosis were seen related to the type of primary tumor, the disease-free interval, the caval or portal type of metastatic spread, the number of metastases and the potential degree of radical resection. The potential degree of conventional radical resections (wedge, anatomical sub-/segmental) was negatively influenced by the number of metastases (n > 9: 79% \"radical\" surgery = 38% 5-year survival). Laser treatment allowed parenchyma-preserving resection in cases of metastases of more than 0.5 cm in diameter, and vaporization in smaller ones. Resection with the intention of achieving complete remission was possible in up to 72 unilateral metastases. The complication rate was comparable to conventional resections."} {"id": "PMID:1280453", "title": "Successful revascularization of large isolated tracheal segments.", "content": "The omentum has been shown to be of use in clinical and experimental revascularization of tracheobronchial anastomoses. We have evaluated the possibility of revascularizing large and completely isolated tracheal segments while preserving the main tracheal characteristics. Ten experiments were performed in dogs, introducing 10-14 cartilage ring tracheal segments enveloped in omentum into the abdomen. Revascularization resulted in all cases with preservation of tracheal consistency. In only two cases were small mucosal necrotic zones observed. The experimental model thus appears to be of use in the revascularization of large tracheal segments, with excellent preservation of both cartilage and mucosa.", "contents": "Successful revascularization of large isolated tracheal segments. The omentum has been shown to be of use in clinical and experimental revascularization of tracheobronchial anastomoses. We have evaluated the possibility of revascularizing large and completely isolated tracheal segments while preserving the main tracheal characteristics. Ten experiments were performed in dogs, introducing 10-14 cartilage ring tracheal segments enveloped in omentum into the abdomen. Revascularization resulted in all cases with preservation of tracheal consistency. In only two cases were small mucosal necrotic zones observed. The experimental model thus appears to be of use in the revascularization of large tracheal segments, with excellent preservation of both cartilage and mucosa."} {"id": "PMID:1280454", "title": "Effects of prostaglandin E2 and cyclic AMP on uptake of immunoglobulin G complexes by cultured macrophages.", "content": "The uptake of immune complexes by macrophages (MP) may be important in disease states in which circulating immune complexes are increased. We undertook the present study to determine the effects of prostaglandin E2 (PGE2) and adenosine 3',5'-cyclic monophosphate (cAMP) on the uptake of immunoglobulin G complexes (IgG complexes) by MP. The uptake of 125I-IgG-gold particles (IgG-gold) was measured in the established MP cell line J774.16 following pretreatment with PGE2, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), PGE2 plus IBMX, the cyclooxygenase inhibitor indomethacin (IM), and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP). Preincubation with PGE2 at concentrations from (10(-12)) to (10(-5) M) revealed significantly diminished uptake of IgG-gold at (10(-6)) and (10(-5) M) (in counts per min per well, PGE2 [10(-6) M], 5,401 +/- 140; control, 17,150 +/- 493, p less than 0.001); (PGE2 [10(-5) M], 3,835 +/- 172; control, 17,150 +/- 493, p less than 0.001). IBMX (10(-3) M) alone did not significantly alter IgG-gold uptake (IBMX, 14,450 +/- 1938; control, 14,840 +/- 995, p less than 1.0). PGE2 (10(-6) M) plus IBMX (10(-3) M) significantly suppressed IgG-gold uptake (in counts per min per well, PGE2 plus IBMX, 3,659 +/- 129; control 18,296 +/- 486, p less than 0.001). PGE2 (10(-6) M) alone also suppressed IgG-gold uptake versus control (PGE2, 4,578 +/- 105; control, 18,296 +/- 486, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of prostaglandin E2 and cyclic AMP on uptake of immunoglobulin G complexes by cultured macrophages. The uptake of immune complexes by macrophages (MP) may be important in disease states in which circulating immune complexes are increased. We undertook the present study to determine the effects of prostaglandin E2 (PGE2) and adenosine 3',5'-cyclic monophosphate (cAMP) on the uptake of immunoglobulin G complexes (IgG complexes) by MP. The uptake of 125I-IgG-gold particles (IgG-gold) was measured in the established MP cell line J774.16 following pretreatment with PGE2, the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX), PGE2 plus IBMX, the cyclooxygenase inhibitor indomethacin (IM), and dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP). Preincubation with PGE2 at concentrations from (10(-12)) to (10(-5) M) revealed significantly diminished uptake of IgG-gold at (10(-6)) and (10(-5) M) (in counts per min per well, PGE2 [10(-6) M], 5,401 +/- 140; control, 17,150 +/- 493, p less than 0.001); (PGE2 [10(-5) M], 3,835 +/- 172; control, 17,150 +/- 493, p less than 0.001). IBMX (10(-3) M) alone did not significantly alter IgG-gold uptake (IBMX, 14,450 +/- 1938; control, 14,840 +/- 995, p less than 1.0). PGE2 (10(-6) M) plus IBMX (10(-3) M) significantly suppressed IgG-gold uptake (in counts per min per well, PGE2 plus IBMX, 3,659 +/- 129; control 18,296 +/- 486, p less than 0.001). PGE2 (10(-6) M) alone also suppressed IgG-gold uptake versus control (PGE2, 4,578 +/- 105; control, 18,296 +/- 486, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280455", "title": "The prostacyclin analogues, cicaprost and iloprost, increase cytosolic Ca2+ concentration in the human erythroleukemia cell line, HEL, via pertussis toxin-insensitive G-proteins.", "content": "In the human erythroleukemia cell line, HEL, prostaglandin E2 (PGE2) and the stable prostacyclin analogue, iloprost, increase cytosolic Ca2+ concentration ([Ca2+]i) via pertussis toxin-sensitive and -insensitive pathways. Unlike iloprost, the stable prostacyclin analogue cicaprost (ZK 96480), is devoid of agonistic properties at prostaglandin E2 receptors. We compared the effects of cicaprost, iloprost and PGE2 on [Ca2+]i in HEL cells. Cicaprost, iloprost and PGE2 were similarly potent to increase [Ca2+]i in HEL cells. However, unlike the effects of PGE2, those of the prostacyclin analogues were not inhibited by pertussis toxin. The prostaglandins studied increased [Ca2+]i through both mobilization from internal stores and Ca2+ influx from the extracellular space. Prostacyclin analogue- and PGE2-induced rises in [Ca2+]i were desensitized in a homologous manner. Additionally, there was cross-desensitization between cicaprost and iloprost, but not between the prostacyclin analogues and PGE2. Our data suggest that in HEL cells (i) cicaprost and iloprost act through prostacyclin receptors and (ii) that these receptors couple to pertussis toxin-insensitive heterotrimeric regulatory guanine nucleotide-binding proteins, (iii) resulting in an increase in [Ca2+]i by Ca2+ mobilization from internal stores and sustained influx.", "contents": "The prostacyclin analogues, cicaprost and iloprost, increase cytosolic Ca2+ concentration in the human erythroleukemia cell line, HEL, via pertussis toxin-insensitive G-proteins. In the human erythroleukemia cell line, HEL, prostaglandin E2 (PGE2) and the stable prostacyclin analogue, iloprost, increase cytosolic Ca2+ concentration ([Ca2+]i) via pertussis toxin-sensitive and -insensitive pathways. Unlike iloprost, the stable prostacyclin analogue cicaprost (ZK 96480), is devoid of agonistic properties at prostaglandin E2 receptors. We compared the effects of cicaprost, iloprost and PGE2 on [Ca2+]i in HEL cells. Cicaprost, iloprost and PGE2 were similarly potent to increase [Ca2+]i in HEL cells. However, unlike the effects of PGE2, those of the prostacyclin analogues were not inhibited by pertussis toxin. The prostaglandins studied increased [Ca2+]i through both mobilization from internal stores and Ca2+ influx from the extracellular space. Prostacyclin analogue- and PGE2-induced rises in [Ca2+]i were desensitized in a homologous manner. Additionally, there was cross-desensitization between cicaprost and iloprost, but not between the prostacyclin analogues and PGE2. Our data suggest that in HEL cells (i) cicaprost and iloprost act through prostacyclin receptors and (ii) that these receptors couple to pertussis toxin-insensitive heterotrimeric regulatory guanine nucleotide-binding proteins, (iii) resulting in an increase in [Ca2+]i by Ca2+ mobilization from internal stores and sustained influx."} {"id": "PMID:1280459", "title": "Long-term outcome and sequelae in aggressive lymphoma patients treated with the LNH-80 regimen.", "content": "One hundred patients with aggressive malignant lymphoma treated with the LNH-80 regimen were evaluated for long-term survival, late relapse and long-term sequelae. The LNH-80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. The fifty-two long-term responders were evaluated for their ability to resume work, sexual function, fertility and presence of long-term sequelae. Of the 41 patients who worked before diagnosis of their disease, 66% had resumed their normal jobs and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) were considered to have mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had second neoplasias. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity.", "contents": "Long-term outcome and sequelae in aggressive lymphoma patients treated with the LNH-80 regimen. One hundred patients with aggressive malignant lymphoma treated with the LNH-80 regimen were evaluated for long-term survival, late relapse and long-term sequelae. The LNH-80 regimen consisted of three intensive courses of adriamycin, cyclophosphamide, vindesine and bleomycin, followed by consolidation and final intensification, as previously described. Of the eighty-four patients who achieved CR after induction, fifty-two are alive in continuous complete remission with a median follow-up of 9.2 years. Twenty-nine CR patients (35%) relapsed. Sixty-six percent of the relapses occurred during the first 18 months following the end of treatment but late relapses were observed up to 7 years off-therapy. The fifty-two long-term responders were evaluated for their ability to resume work, sexual function, fertility and presence of long-term sequelae. Of the 41 patients who worked before diagnosis of their disease, 66% had resumed their normal jobs and 24% had retired. Sexual activity was considered to be satisfactory by 66% of the patients. Eleven of the 15 patients (73%) who wanted children had between one and three children. Seven patients (14%) were considered to have mild long-term sequelae but all long-term survivors reported having an acceptable quality of life. Five of the patients who reached CR (6%) had second neoplasias. The LNH-80 regimen allowed 52% of the patients to benefit from long-term disease-free survival with minor long-term toxicity."} {"id": "PMID:1280458", "title": "Vehicle pollutants: effects on the lung.", "content": "As concern about pollution of the environment and the consequent effects on health grows nationally and internationally, the role of the nurse as health promoter is increasing in importance. The Royal College of Nursing responded to this concern by establishing an Environmental Working Party, of which the author is a member. This article considers one type of pollution, that caused by vehicles, and its effects on the functioning of the lung. The author argues that nurses need to be familiar with environmental determinants of health if they are to work towards upholding a 'health' service.", "contents": "Vehicle pollutants: effects on the lung. As concern about pollution of the environment and the consequent effects on health grows nationally and internationally, the role of the nurse as health promoter is increasing in importance. The Royal College of Nursing responded to this concern by establishing an Environmental Working Party, of which the author is a member. This article considers one type of pollution, that caused by vehicles, and its effects on the functioning of the lung. The author argues that nurses need to be familiar with environmental determinants of health if they are to work towards upholding a 'health' service."} {"id": "PMID:1280460", "title": "Chemotherapy with MACOP-B and VACOP-B for intermediate- and high-grade non-Hodgkin's lymphoma: clinical results and analysis of prognostic factors.", "content": "Eighty-three previously untreated patients with aggressive non-Hodgkin's lymphomas were treated with either MACOP-B (23 patients) or VACOP-B (60 patients) as originally described by Klimo and Conners [1, 2]. Their median age was 46 years. Thirty-seven patients had stage I or II and 46 stage III or IV disease. The tumor histopathology was reviewed in all cases. Sixty-five patients had intermediate grade and 18 high-grade non-Hodgkin's lymphomas according to the International Working Formulation. The rate of complete response was 74% for MACOP-B and 76% for VACOP-B. At the time of analysis the duration of follow-up was 50 months for the MACOP-B and 22 months for the VACOP-B group. The actuarial three-year progression-free survival was 35 +/- 10% for the MACOP-B group, 48 +/- 11% for the VACOP-B group, and 46 +/- 7% for all patients. Treatment mortality was 6%. A univariate and a multivariate analysis of selected pretreatment parameters and of regimen demonstrated that stage III or IV, high-grade lymphoma, and elevated serum LDH, but not the type of regimen, are significantly associated with poor progression-free survival in our patient population.", "contents": "Chemotherapy with MACOP-B and VACOP-B for intermediate- and high-grade non-Hodgkin's lymphoma: clinical results and analysis of prognostic factors. Eighty-three previously untreated patients with aggressive non-Hodgkin's lymphomas were treated with either MACOP-B (23 patients) or VACOP-B (60 patients) as originally described by Klimo and Conners [1, 2]. Their median age was 46 years. Thirty-seven patients had stage I or II and 46 stage III or IV disease. The tumor histopathology was reviewed in all cases. Sixty-five patients had intermediate grade and 18 high-grade non-Hodgkin's lymphomas according to the International Working Formulation. The rate of complete response was 74% for MACOP-B and 76% for VACOP-B. At the time of analysis the duration of follow-up was 50 months for the MACOP-B and 22 months for the VACOP-B group. The actuarial three-year progression-free survival was 35 +/- 10% for the MACOP-B group, 48 +/- 11% for the VACOP-B group, and 46 +/- 7% for all patients. Treatment mortality was 6%. A univariate and a multivariate analysis of selected pretreatment parameters and of regimen demonstrated that stage III or IV, high-grade lymphoma, and elevated serum LDH, but not the type of regimen, are significantly associated with poor progression-free survival in our patient population."} {"id": "PMID:1280462", "title": "The Second International Symposium on Hodgkin's Disease. Workshop III: Recommendations for future clinical trials.", "content": "In the opinion of the participants of the workshop, the following problems should be addressed with high priority: 1st, a clear definition of the 10%-15% of patients who should receive radiotherapy only; 2nd, reduction of toxicity of combined modality approaches for patients in localized stages with risk factors; and 3rd, definition of a poor-prognosis subgroup of patients in stages IIIB/IV for whom more efficient treatment programs must be developed. Dose intensification in the form of ABMT as the prominent example of high dose intensity should be tested in these patients. If this approach proves its efficacy, the concept of dose intensification could be extended to other patients with advanced disease. Results of recent trials in Hodgkin's disease suggest that the cure rates which increased considerably between 1960 and 1980 have reached a plateau. Further improvements that can be realistically expected will be small and studies to prove such progress need large numbers of patients ('megatrials') to avoid 'false negative' results. Such megatrials could be performed as large international or even intercontinental trials. To some extent, overviews could substitute for megatrials, if sufficient high-quality randomized studies addressing a specific question are available for a meta-analysis. The installation of an international steering committee was recommended, which should stimulate and coordinate world-wide efforts for the solution of the remaining problems in the treatment of Hodgkin's disease.", "contents": "The Second International Symposium on Hodgkin's Disease. Workshop III: Recommendations for future clinical trials. In the opinion of the participants of the workshop, the following problems should be addressed with high priority: 1st, a clear definition of the 10%-15% of patients who should receive radiotherapy only; 2nd, reduction of toxicity of combined modality approaches for patients in localized stages with risk factors; and 3rd, definition of a poor-prognosis subgroup of patients in stages IIIB/IV for whom more efficient treatment programs must be developed. Dose intensification in the form of ABMT as the prominent example of high dose intensity should be tested in these patients. If this approach proves its efficacy, the concept of dose intensification could be extended to other patients with advanced disease. Results of recent trials in Hodgkin's disease suggest that the cure rates which increased considerably between 1960 and 1980 have reached a plateau. Further improvements that can be realistically expected will be small and studies to prove such progress need large numbers of patients ('megatrials') to avoid 'false negative' results. Such megatrials could be performed as large international or even intercontinental trials. To some extent, overviews could substitute for megatrials, if sufficient high-quality randomized studies addressing a specific question are available for a meta-analysis. The installation of an international steering committee was recommended, which should stimulate and coordinate world-wide efforts for the solution of the remaining problems in the treatment of Hodgkin's disease."} {"id": "PMID:1280463", "title": "Long-term gonadal dysfunction and its impact on bone mineralization in patients following COPP/ABVD chemotherapy for Hodgkin's disease.", "content": "Only limited data is currently available on long-term gonadal toxicity and its impact on bone mineralization in men and women treated for Hodgkin's disease. The present study was therefore conducted to evaluate gonadal toxicity and bone loss in 49 patients with Hodgkin's disease 2-10 (median 5.37) years after chemotherapy. Most patients were treated with the COPP/ABVD regimen +/- irradiation according to the protocols of the German Hodgkin Study Group. Blood samples were tested for gonadotropins (FSH, LH), gonadal steroids, parathyroid hormone, osteocalcin, and calcitonin. Bone mineral density was measured using single- and dual-energy quantitative computed tomography as well as single-photon absorptiometry. FSH serum levels were significantly increased in 21/27 (80%) men demonstrating germ-cell aplasia. 13/15 (86%) men showed azoospermia after the COPP/ABVD regimen. In contrast, testosterone levels were within normal limits in all men tested, suggesting normal Leydig-cell function. 17/22 (77%) women exhibited increased FSH and LH levels, indicating premature ovarian failure. Women with therapy-induced ovarian failure had a significantly lower trabecular (98 +/- 34) and cortical (292 +/- 48 mg/cm3) spinal bone density than those with normal ovarian function. Men showed no evidence of bone loss after therapy. These data suggest severe gonadal toxicity in both men and women treated with the COPP/ABVD regimen. In female patients, drug-induced ovarian failure has a significant impact on bone mineralization.", "contents": "Long-term gonadal dysfunction and its impact on bone mineralization in patients following COPP/ABVD chemotherapy for Hodgkin's disease. Only limited data is currently available on long-term gonadal toxicity and its impact on bone mineralization in men and women treated for Hodgkin's disease. The present study was therefore conducted to evaluate gonadal toxicity and bone loss in 49 patients with Hodgkin's disease 2-10 (median 5.37) years after chemotherapy. Most patients were treated with the COPP/ABVD regimen +/- irradiation according to the protocols of the German Hodgkin Study Group. Blood samples were tested for gonadotropins (FSH, LH), gonadal steroids, parathyroid hormone, osteocalcin, and calcitonin. Bone mineral density was measured using single- and dual-energy quantitative computed tomography as well as single-photon absorptiometry. FSH serum levels were significantly increased in 21/27 (80%) men demonstrating germ-cell aplasia. 13/15 (86%) men showed azoospermia after the COPP/ABVD regimen. In contrast, testosterone levels were within normal limits in all men tested, suggesting normal Leydig-cell function. 17/22 (77%) women exhibited increased FSH and LH levels, indicating premature ovarian failure. Women with therapy-induced ovarian failure had a significantly lower trabecular (98 +/- 34) and cortical (292 +/- 48 mg/cm3) spinal bone density than those with normal ovarian function. Men showed no evidence of bone loss after therapy. These data suggest severe gonadal toxicity in both men and women treated with the COPP/ABVD regimen. In female patients, drug-induced ovarian failure has a significant impact on bone mineralization."} {"id": "PMID:1280464", "title": "Role of additional radiotherapy in advanced stages of Hodgkin's disease.", "content": "Although radiotherapy is widely used as additional treatment following chemotherapy, its precise role has never been clearly proven. Relapses tend to occur in previously involved bulky sites. Non-randomized studies may suggest a positive effect of the addition of radiotherapy. This effect however, might also be caused by selection. Randomized studies have not resulted in a survival advantage for the patients treated with additional radiotherapy compared to no further treatment or additional chemotherapy. The SWOG study 7808 suggest a 20% benefit in remission duration for the nodular sclerosis histology subgroup. Definitive conclusions have to wait for more mature results of randomized studies including the ongoing EORTC study and the possibility to perform an overview of all studies.", "contents": "Role of additional radiotherapy in advanced stages of Hodgkin's disease. Although radiotherapy is widely used as additional treatment following chemotherapy, its precise role has never been clearly proven. Relapses tend to occur in previously involved bulky sites. Non-randomized studies may suggest a positive effect of the addition of radiotherapy. This effect however, might also be caused by selection. Randomized studies have not resulted in a survival advantage for the patients treated with additional radiotherapy compared to no further treatment or additional chemotherapy. The SWOG study 7808 suggest a 20% benefit in remission duration for the nodular sclerosis histology subgroup. Definitive conclusions have to wait for more mature results of randomized studies including the ongoing EORTC study and the possibility to perform an overview of all studies."} {"id": "PMID:1280466", "title": "Polymorphonuclear leukocyte adhesion to endothelial cells is inhibited by resting platelets.", "content": "The effect of human platelets on the adhesion of polymorphonuclear leukocytes (PMNs) to cultured endothelial cells was investigated. Resting platelets inhibited the adhesion of PMNs stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4), and tumor necrosis factor-alpha (TNF-alpha). Platelets similarly inhibited PMN adhesion induced by endothelial cell activation with TNF-alpha. The inhibitory effect depended on platelet number, was not associated with detectable platelet activation, and was also exerted by paraformaldehyde-fixed platelets. Moreover, supernatants of U46619- or thrombin-stimulated platelets were ineffective, thus excluding a role for constituents released as a result of the platelet-release reaction. Strong inhibition of PMN adhesion was exerted by platelet lysates. The inhibitory activity associated with lysates was sedimentable, heat sensitive, and not dialyzable through a membrane with a molecular-weight cutoff of 8,000; it was directed toward PMNs and was not due to cytotoxic effects or a general inhibition of PMN responsiveness to stimulation, since enzymatic release from activated PMNs was unaffected by platelet lysates. Finally, the activity was not prevented by specific adenosine inhibitors and anti-P-selectin monoclonal antibody. These data suggest that resting platelets can exert an inhibitory effect on PMN adhesion to the vessel wall during inflammatory and thrombotic conditions.", "contents": "Polymorphonuclear leukocyte adhesion to endothelial cells is inhibited by resting platelets. The effect of human platelets on the adhesion of polymorphonuclear leukocytes (PMNs) to cultured endothelial cells was investigated. Resting platelets inhibited the adhesion of PMNs stimulated by N-formyl-methionyl-leucyl-phenylalanine (fMLP), leukotriene B4 (LTB4), and tumor necrosis factor-alpha (TNF-alpha). Platelets similarly inhibited PMN adhesion induced by endothelial cell activation with TNF-alpha. The inhibitory effect depended on platelet number, was not associated with detectable platelet activation, and was also exerted by paraformaldehyde-fixed platelets. Moreover, supernatants of U46619- or thrombin-stimulated platelets were ineffective, thus excluding a role for constituents released as a result of the platelet-release reaction. Strong inhibition of PMN adhesion was exerted by platelet lysates. The inhibitory activity associated with lysates was sedimentable, heat sensitive, and not dialyzable through a membrane with a molecular-weight cutoff of 8,000; it was directed toward PMNs and was not due to cytotoxic effects or a general inhibition of PMN responsiveness to stimulation, since enzymatic release from activated PMNs was unaffected by platelet lysates. Finally, the activity was not prevented by specific adenosine inhibitors and anti-P-selectin monoclonal antibody. These data suggest that resting platelets can exert an inhibitory effect on PMN adhesion to the vessel wall during inflammatory and thrombotic conditions."} {"id": "PMID:1280468", "title": "Injury of mouse lymphocytes caused by exogenous methyl linoleate hydroperoxides in vitro.", "content": "The incubation with methyl linoleate hydroperoxides (MLHPO), a model of lipid peroxides, depressed DNA, RNA and protein syntheses of mouse thymic lymphocytes and increased the amount of thiobarbituric acid-reactive substances in lymphocytes. These phenomena were also found in the splenic lymphoblasts in the DNA synthetic phase (S-phase) obtained by mitogen. Prior culturing with all-rac-alpha-tocopherol increased DNA synthesis in splenic lymphoblasts. Electron microscopically, cytoplasmic micro-organelles of splenic lymphoblasts in the S- and G2-phases were markedly destroyed as compared with nuclei. No discernible changes were observed in not-blastotransformed lymphocytes under these experimental conditions. These findings indicate that thymic lymphocytes and splenic lymphoblasts are affected by exogenous lipid peroxides, and cytoplasmic micro-organelles of splenic lymphoblasts might be markedly damaged by exogenous lipid peroxides as compared to their nuclei.", "contents": "Injury of mouse lymphocytes caused by exogenous methyl linoleate hydroperoxides in vitro. The incubation with methyl linoleate hydroperoxides (MLHPO), a model of lipid peroxides, depressed DNA, RNA and protein syntheses of mouse thymic lymphocytes and increased the amount of thiobarbituric acid-reactive substances in lymphocytes. These phenomena were also found in the splenic lymphoblasts in the DNA synthetic phase (S-phase) obtained by mitogen. Prior culturing with all-rac-alpha-tocopherol increased DNA synthesis in splenic lymphoblasts. Electron microscopically, cytoplasmic micro-organelles of splenic lymphoblasts in the S- and G2-phases were markedly destroyed as compared with nuclei. No discernible changes were observed in not-blastotransformed lymphocytes under these experimental conditions. These findings indicate that thymic lymphocytes and splenic lymphoblasts are affected by exogenous lipid peroxides, and cytoplasmic micro-organelles of splenic lymphoblasts might be markedly damaged by exogenous lipid peroxides as compared to their nuclei."} {"id": "PMID:1280469", "title": "Pharmacological modulation of the endotoxin-induced increase in plasminogen activator inhibitor activity in rats.", "content": "Pharmacological modulation of the in vivo induction of plasminogen activator inhibitor type-1 (PAI-1) synthesis was studied in rats using the induction of PAI-1 by endotoxin as a model system. Both the cyclooxygenase inhibitors acetylsalicylic acid and indomethacin enhanced PAI-1 induction. The combined cyclooxygenase-lipoxygenase inhibitor, BW755C, dose-dependently inhibited induction. Since five other lipoxygenase inhibitors, a phospholipase inhibitor, an inhibitor of leukotriene formation and dexamethasone had no effect on the endotoxin-induced increase in PAI-1 synthesis, the effect of BW755C could not be ascribed to its known pharmacological properties. In addition, induction of PAI was enhanced by isobutyl-methylxanthine, a phosphodiesterase inhibitor, but not, however, by other phosphodiesterase inhibitors, or by forskolin or NG-nitro-L-arginine, suggesting an effect of isobutyl-methylxanthine other than through cyclic nucleotides. Heparin and hirudin had no effect either. Overall, the data showed that the induction of PAI-1 synthesis by endotoxin in vivo can be up- and down-regulated pharmacologically, but the mechanisms involved remain elusive.", "contents": "Pharmacological modulation of the endotoxin-induced increase in plasminogen activator inhibitor activity in rats. Pharmacological modulation of the in vivo induction of plasminogen activator inhibitor type-1 (PAI-1) synthesis was studied in rats using the induction of PAI-1 by endotoxin as a model system. Both the cyclooxygenase inhibitors acetylsalicylic acid and indomethacin enhanced PAI-1 induction. The combined cyclooxygenase-lipoxygenase inhibitor, BW755C, dose-dependently inhibited induction. Since five other lipoxygenase inhibitors, a phospholipase inhibitor, an inhibitor of leukotriene formation and dexamethasone had no effect on the endotoxin-induced increase in PAI-1 synthesis, the effect of BW755C could not be ascribed to its known pharmacological properties. In addition, induction of PAI was enhanced by isobutyl-methylxanthine, a phosphodiesterase inhibitor, but not, however, by other phosphodiesterase inhibitors, or by forskolin or NG-nitro-L-arginine, suggesting an effect of isobutyl-methylxanthine other than through cyclic nucleotides. Heparin and hirudin had no effect either. Overall, the data showed that the induction of PAI-1 synthesis by endotoxin in vivo can be up- and down-regulated pharmacologically, but the mechanisms involved remain elusive."} {"id": "PMID:1280470", "title": "Contact factor proteases and the complexes formed with alpha 2-macroglobulin can interfere in protein C assays by cleaving amidolytic substrates.", "content": "Plasma from women taking combined oral contraceptives and cold-activated plasma contain proteases which cleave chromogenic substrates in protein C assays in the absence of protein C activators such as Protac. This spontaneous activity makes a background substraction necessary and makes protein C (PC) assays less accurate. We investigated two commonly used substrates < Glu-Pro-Arg-pNA (S-2366) and 2AcOH.H-D-Lys(Cbo)-Pro-Arg-pNA (PC substrate) and found that cold-activated normal and protein C-deficient plasmas gave absorbance values up to 300 times higher than buffer blanks. FXIa cleaves these substrates but activity was not blocked by corn or lima bean trypsin inhibitors, soy bean trypsin inhibitor (SBTI), hirudin or epsilon-amino-n-caproic acid (EACA). Kaolin activation of normal, FXI, FIX, FVIII, FVII and protein C-deficient, but not of FXII or prekallikrein (PKK)-deficient plasmas led to cleavage of chromogenic substrate for protein C. The protein C substrates were cleaved by purified kallikrein and alpha- and beta-FXIIa. Immunoabsorption with alpha 2-macroglobulin (alpha 2M) antibodies removed 60% of the alpha 2M and 70% of the activity on PC Substrate. Gel filtration of normal plasma on Sephadex G-150 gave a single peak of protein C activity and antigen in the included volume. After cold activation of the fractions, a second protein C-like peak appeared in the void volume, but with no detectable protein C antigen. This peak coincided with alpha 2M (chromogenic and ELISA) and plasma kallikrein (S-2302), but FXII (measured with a substrate insensitive to kallikrein) eluted separately.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Contact factor proteases and the complexes formed with alpha 2-macroglobulin can interfere in protein C assays by cleaving amidolytic substrates. Plasma from women taking combined oral contraceptives and cold-activated plasma contain proteases which cleave chromogenic substrates in protein C assays in the absence of protein C activators such as Protac. This spontaneous activity makes a background substraction necessary and makes protein C (PC) assays less accurate. We investigated two commonly used substrates < Glu-Pro-Arg-pNA (S-2366) and 2AcOH.H-D-Lys(Cbo)-Pro-Arg-pNA (PC substrate) and found that cold-activated normal and protein C-deficient plasmas gave absorbance values up to 300 times higher than buffer blanks. FXIa cleaves these substrates but activity was not blocked by corn or lima bean trypsin inhibitors, soy bean trypsin inhibitor (SBTI), hirudin or epsilon-amino-n-caproic acid (EACA). Kaolin activation of normal, FXI, FIX, FVIII, FVII and protein C-deficient, but not of FXII or prekallikrein (PKK)-deficient plasmas led to cleavage of chromogenic substrate for protein C. The protein C substrates were cleaved by purified kallikrein and alpha- and beta-FXIIa. Immunoabsorption with alpha 2-macroglobulin (alpha 2M) antibodies removed 60% of the alpha 2M and 70% of the activity on PC Substrate. Gel filtration of normal plasma on Sephadex G-150 gave a single peak of protein C activity and antigen in the included volume. After cold activation of the fractions, a second protein C-like peak appeared in the void volume, but with no detectable protein C antigen. This peak coincided with alpha 2M (chromogenic and ELISA) and plasma kallikrein (S-2302), but FXII (measured with a substrate insensitive to kallikrein) eluted separately.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280471", "title": "Antenatal care for the normal patient.", "content": "Screening protocols for low-risk obstetric patients are used to identify those at risk for adverse perinatal outcome. Gestational diabetes screening is best performed by administering 50 g of glucose in the nonfasting state, with plasma glucose values above 140 mg/dL at 1 hour considered abnormal. Assay of maternal serum alpha-fetoprotein is primarily used to identify pregnancies at risk for neural tube defects and other structural anomalies. However, an elevated value may also identify patients at increased risk for a number of abnormal pregnancy outcomes, even when the fetus is free from defects. Patients who have previously had a cesarean section are now strongly encouraged to undergo a trial of labor and to attempt a vaginal birth. Such a course is not without risk, and catastrophic complications can develop. Careful patient selection, appropriate counseling, and close management are necessary in this situation.", "contents": "Antenatal care for the normal patient. Screening protocols for low-risk obstetric patients are used to identify those at risk for adverse perinatal outcome. Gestational diabetes screening is best performed by administering 50 g of glucose in the nonfasting state, with plasma glucose values above 140 mg/dL at 1 hour considered abnormal. Assay of maternal serum alpha-fetoprotein is primarily used to identify pregnancies at risk for neural tube defects and other structural anomalies. However, an elevated value may also identify patients at increased risk for a number of abnormal pregnancy outcomes, even when the fetus is free from defects. Patients who have previously had a cesarean section are now strongly encouraged to undergo a trial of labor and to attempt a vaginal birth. Such a course is not without risk, and catastrophic complications can develop. Careful patient selection, appropriate counseling, and close management are necessary in this situation."} {"id": "PMID:1280472", "title": "Lectin characterization of cystogenesis in the SBM transgenic model of polycystic kidney disease.", "content": "The generation of a novel transgenic mouse model of polycystic kidney disease with a construct (SBM) that links the coding region of the c-myc proto-oncogene to the simian virus 40 enhancer and beta-globin promoter was previously reported (see reference 1). In order to determine the site of origin and histogenesis of renal cysts in this model, lectin/immunohistochemical and electron microscopic studies on mice of varying ages (from birth to adulthood) are described here. Cysts are detectable at birth and increase in number and diameter with age. Cysts predominantly involve the collecting tubules of young transgenic mice but progressively affect the proximal tubules with advancing age. A minority of cysts are of distal tubular origin in all age groups studied. Tubular hyperplasias are primarily reactive with proximal tubular markers and appear to precede the development of proximal tubular cysts in adult mice. This particular phenotypic evolution of polycystic kidney disease with advancing age suggests that the cystogenic potential of the transgene is modulated by yet unidentified tubular segment-specific responses.", "contents": "Lectin characterization of cystogenesis in the SBM transgenic model of polycystic kidney disease. The generation of a novel transgenic mouse model of polycystic kidney disease with a construct (SBM) that links the coding region of the c-myc proto-oncogene to the simian virus 40 enhancer and beta-globin promoter was previously reported (see reference 1). In order to determine the site of origin and histogenesis of renal cysts in this model, lectin/immunohistochemical and electron microscopic studies on mice of varying ages (from birth to adulthood) are described here. Cysts are detectable at birth and increase in number and diameter with age. Cysts predominantly involve the collecting tubules of young transgenic mice but progressively affect the proximal tubules with advancing age. A minority of cysts are of distal tubular origin in all age groups studied. Tubular hyperplasias are primarily reactive with proximal tubular markers and appear to precede the development of proximal tubular cysts in adult mice. This particular phenotypic evolution of polycystic kidney disease with advancing age suggests that the cystogenic potential of the transgene is modulated by yet unidentified tubular segment-specific responses."} {"id": "PMID:1280473", "title": "Evidence for sense RNA-mediated protection to PVYN in tobacco plants transformed with the viral coat protein cistron.", "content": "The coat protein (CP) cistron of the tobacco veinal necrosis strain of potato virus Y (PVYN), supplemented with translational start signals, was cloned into an Agrobacterium tumefaciens Ti transformation vector. Transformation of tobacco leaf discs resulted in 99 transgenic lines which were subsequently analysed for the presence and expression, at both the transcriptional and translational level, of the CP-gene. Although CP-specific RNA transcripts were produced in all plants no CP could be detected by several sensitive immunological techniques. Upon mechanical inoculation of progeny lines of self-pollinated original transformants (S1) with PVYN, protection levels of 20 and 95%, respectively, could be observed in two out of ten lines tested. This level of protection increased to 100% in the S2 progeny obtained from self-pollination of virus-protected S1 plants. Transformation of tobacco leaf discs with a PVYN CP construct from which the ATG start codon had been removed by site-directed mutagenesis resulted in 57 transgenic lines that all produced CP-specific transcripts. Mechanical inoculation with PVYN of S1 progeny plants of several of these lines resulted in resistance to a similar level and extent as in the S1 progeny of plants transformed with the intact CP cistron. The results obtained strongly suggest that the resistance observed in the transgenic plants is principally based on the presence of PVYN CP RNA sequences rather than on the accumulation of viral coat protein.", "contents": "Evidence for sense RNA-mediated protection to PVYN in tobacco plants transformed with the viral coat protein cistron. The coat protein (CP) cistron of the tobacco veinal necrosis strain of potato virus Y (PVYN), supplemented with translational start signals, was cloned into an Agrobacterium tumefaciens Ti transformation vector. Transformation of tobacco leaf discs resulted in 99 transgenic lines which were subsequently analysed for the presence and expression, at both the transcriptional and translational level, of the CP-gene. Although CP-specific RNA transcripts were produced in all plants no CP could be detected by several sensitive immunological techniques. Upon mechanical inoculation of progeny lines of self-pollinated original transformants (S1) with PVYN, protection levels of 20 and 95%, respectively, could be observed in two out of ten lines tested. This level of protection increased to 100% in the S2 progeny obtained from self-pollination of virus-protected S1 plants. Transformation of tobacco leaf discs with a PVYN CP construct from which the ATG start codon had been removed by site-directed mutagenesis resulted in 57 transgenic lines that all produced CP-specific transcripts. Mechanical inoculation with PVYN of S1 progeny plants of several of these lines resulted in resistance to a similar level and extent as in the S1 progeny of plants transformed with the intact CP cistron. The results obtained strongly suggest that the resistance observed in the transgenic plants is principally based on the presence of PVYN CP RNA sequences rather than on the accumulation of viral coat protein."} {"id": "PMID:1280474", "title": "Clinical application of radioimmunoimaging in the detection of tumors--current status in China.", "content": "In this article, the development of radioimmunoimaging (RII) in China is reviewed. Since 1984 conventional heterologous specific antibodies (Abs), such as anti-carcinoembryonic antigen (CEA) and anti-alphafetoprotein (AFP) Abs, have been used to detect cancers of the colon, ovary, lung, liver, etc. Later on, Abs against specific tumor cell-associated antigens have been produced in many institutions and applied clinically, with quite satisfactory results (detection rate ranging from 80-90%). Recently, human monoclonal antibodies (McAbs) are also being prepared. Finally, the existing problems to be overcome are discussed.", "contents": "Clinical application of radioimmunoimaging in the detection of tumors--current status in China. In this article, the development of radioimmunoimaging (RII) in China is reviewed. Since 1984 conventional heterologous specific antibodies (Abs), such as anti-carcinoembryonic antigen (CEA) and anti-alphafetoprotein (AFP) Abs, have been used to detect cancers of the colon, ovary, lung, liver, etc. Later on, Abs against specific tumor cell-associated antigens have been produced in many institutions and applied clinically, with quite satisfactory results (detection rate ranging from 80-90%). Recently, human monoclonal antibodies (McAbs) are also being prepared. Finally, the existing problems to be overcome are discussed."} {"id": "PMID:1280475", "title": "Pilot production of high-titer interferon and virus with a microcarrier suspension culture system.", "content": "We have successfully cultured four cell lines--L929, BHK-13, BHK-21 and CHO-K1 using an MC-1 type microcarrier made in our academy. With the microcarrier in a concentration of 5 mg/ml, the cell density was about 30 x 10(4) cells/ml; after 3 days in suspension culture, the cells could proliferate to 1 x 10(6) cells/ml. At this time, when L929 cells were primed with 25 IU/ml MuIFN for 14-24 h and then superinduced with NDV, cycloheximide (20 micrograms/ml) and actinomycin D (2 micrograms/ml), the titer of IFN reached approximately 10(5) IU/ml (10(5) IU/mg of protein, expressed in specific activity). When VSV was inoculated into the other three cell line cultures, the viral titer reached 6 Log TCID50/ml or much higher. The yield with the CHO-K1 cell line was the highest, reaching titers of 7-8 Log TCID50/ml. These titers were similar to those seen in stationary culture. With trypsin-citrate solution and a more rapid stirring speed, the cells could be satisfactorily released from the microcarriers and reattached on fresh ones. These experiments show that the microcarrier suspension culture system is suitable for producing large scale, high-titer, low-cost vaccines and IFNs, both natural and recombinant, using genetically-engineered CHO cell lines.", "contents": "Pilot production of high-titer interferon and virus with a microcarrier suspension culture system. We have successfully cultured four cell lines--L929, BHK-13, BHK-21 and CHO-K1 using an MC-1 type microcarrier made in our academy. With the microcarrier in a concentration of 5 mg/ml, the cell density was about 30 x 10(4) cells/ml; after 3 days in suspension culture, the cells could proliferate to 1 x 10(6) cells/ml. At this time, when L929 cells were primed with 25 IU/ml MuIFN for 14-24 h and then superinduced with NDV, cycloheximide (20 micrograms/ml) and actinomycin D (2 micrograms/ml), the titer of IFN reached approximately 10(5) IU/ml (10(5) IU/mg of protein, expressed in specific activity). When VSV was inoculated into the other three cell line cultures, the viral titer reached 6 Log TCID50/ml or much higher. The yield with the CHO-K1 cell line was the highest, reaching titers of 7-8 Log TCID50/ml. These titers were similar to those seen in stationary culture. With trypsin-citrate solution and a more rapid stirring speed, the cells could be satisfactorily released from the microcarriers and reattached on fresh ones. These experiments show that the microcarrier suspension culture system is suitable for producing large scale, high-titer, low-cost vaccines and IFNs, both natural and recombinant, using genetically-engineered CHO cell lines."} {"id": "PMID:1280476", "title": "The ligand for c-kit, stem cell factor, stimulates the circulation of cells that engraft lethally irradiated baboons.", "content": "Recombinant human stem cell factor (SCF), the ligand for c-kit, has been shown to stimulate increased numbers of hematopoietic progenitor cells of multiple types to circulate in the blood of baboons, but it was not known if the cells stimulated to circulate by SCF contained cells capable of engrafting and rescuing lethally irradiated baboons. Peripheral blood mononuclear cells (PBMNC) were collected by leukapheresis from four untreated control baboons and from three baboons on the 10th or 11th day of treatment with SCF (200 micrograms/kg/d). All animals were transplanted with 1.00 to 1.04 x 10(8)/kg of cryopreserved autologous PBMNC after treatment with a single dose of 1,020 cGy total body irradiation (TBI). Three animals were transplanted with PBMNC that had been collected during SCF treatment, 24 to 38 days after the last dose of SCF. Rapid trilineage engraftment was documented by bone marrow biopsy in all three. The mean time to a total white blood cell count (WBC) > or = 500/microL, WBC > or = 1,000/microL, and an absolute neutrophil count (ANC) > or = 500/microL was 15 +/- 3 (mean +/- SD), 19 +/- 1, and 19 +/- 2 days, respectively. Two animals remain alive with stable engraftment more than 180 and 245 days posttransplant. The third died of sepsis 32 days posttransplant with a hypercellular marrow showing trilineage engraftment. The surviving animals were transfusion independent by 10 and 59 days posttransplant. Four control animals were transplanted with PBMNC collected in the absence of SCF stimulation. One was treated for 11 days with SCF (200 micrograms/kg/d) after PBMNC were collected. This animal was transplanted 25 days after the last dose of SCF. None of the four control animals engrafted and they died 13, 16, 28, and 38 days posttransplant with marrow aplasia. Treatment with SCF stimulates the circulation of cells that engraft and rescue lethally irradiated baboons. The characteristics of the transplantable cells present in the circulation are now amenable to direct study.", "contents": "The ligand for c-kit, stem cell factor, stimulates the circulation of cells that engraft lethally irradiated baboons. Recombinant human stem cell factor (SCF), the ligand for c-kit, has been shown to stimulate increased numbers of hematopoietic progenitor cells of multiple types to circulate in the blood of baboons, but it was not known if the cells stimulated to circulate by SCF contained cells capable of engrafting and rescuing lethally irradiated baboons. Peripheral blood mononuclear cells (PBMNC) were collected by leukapheresis from four untreated control baboons and from three baboons on the 10th or 11th day of treatment with SCF (200 micrograms/kg/d). All animals were transplanted with 1.00 to 1.04 x 10(8)/kg of cryopreserved autologous PBMNC after treatment with a single dose of 1,020 cGy total body irradiation (TBI). Three animals were transplanted with PBMNC that had been collected during SCF treatment, 24 to 38 days after the last dose of SCF. Rapid trilineage engraftment was documented by bone marrow biopsy in all three. The mean time to a total white blood cell count (WBC) > or = 500/microL, WBC > or = 1,000/microL, and an absolute neutrophil count (ANC) > or = 500/microL was 15 +/- 3 (mean +/- SD), 19 +/- 1, and 19 +/- 2 days, respectively. Two animals remain alive with stable engraftment more than 180 and 245 days posttransplant. The third died of sepsis 32 days posttransplant with a hypercellular marrow showing trilineage engraftment. The surviving animals were transfusion independent by 10 and 59 days posttransplant. Four control animals were transplanted with PBMNC collected in the absence of SCF stimulation. One was treated for 11 days with SCF (200 micrograms/kg/d) after PBMNC were collected. This animal was transplanted 25 days after the last dose of SCF. None of the four control animals engrafted and they died 13, 16, 28, and 38 days posttransplant with marrow aplasia. Treatment with SCF stimulates the circulation of cells that engraft and rescue lethally irradiated baboons. The characteristics of the transplantable cells present in the circulation are now amenable to direct study."} {"id": "PMID:1280477", "title": "In vivo effects of interleukin-6 on thrombopoiesis in healthy and irradiated primates.", "content": "We have studied the in vivo effects of recombinant human interleukin-6 (rhIL-6) on hematopoiesis in eight healthy and nine irradiated cynomolgus monkeys. Of the healthy animals, three received rhIL-6 alone (10 micrograms/kg/d, subcutaneously [SC]), one received rhIL-6 in combination with rhIL-3 (10 micrograms/kg/d, SC), one received rhIL-6 in combination with recombinant cynomolgus granulocyte-macrophage colony-stimulating factor (rcGM-CSF; 10 micrograms/kg/d, SC), two received rhIL-6 in combination with recombinant human granulocyte-CSF (rhG-CSF; 10 micrograms/kg/d, SC), and one received rhIL-6 in combination with recombinant human leukemia inhibitory factor (rhLIF; 10 micrograms/kg/d, SC). All animals were treated for at least 2 weeks with rhIL-6 or the above mentioned combinations. rhIL-6 alone significantly increased the peripheral blood platelet counts (2- to 3.5-fold). The platelets reached a plateau between days 10 and 15 of treatment. No synergistic effects on platelet numbers were observed when rhIL-6 was combined with rhIL-3, rcGM-CSF, rhG-CSF, or rhLIF. In addition to rhIL-6, only rhLIF increased the platelet numbers when administered alone. To test whether rhIL-6 might also protect the animal from thrombocytopenia or shorten the time of thrombocytopenia after irradiation, we treated nine animals with total body irradiation (3.8 Gy). Six of the animals were additional treated with rhIL-6 (4 with 10 micrograms/kg/d; and 2 with 100 micrograms/kg/d) from day -1 or +1 to day 28 post irradiation. In these animals, rhIL-6 at the same dose effective in healthy animals (10 micrograms/kg/d) was not capable of protecting the animals from platelet nadir. However, when pegylated rhIL-6 was used at a dosage of 100 micrograms/kg/d post irradiation, the mean of the nadirs was 71,000/microL as compared with 39,000/microL in control animals and the time of thrombocytopenia was shorter (3 v 5 days). In all animals (healthy and irradiated), rhIL-6 did not increase the number of bone marrow megakaryocytes but induced a right shift of DNA ploidy in megakaryocytes. These data suggest that IL-6 acts as \"thrombopoietin\"-like activity, but not as \"megakaryocyte-CSF\"-like activity.", "contents": "In vivo effects of interleukin-6 on thrombopoiesis in healthy and irradiated primates. We have studied the in vivo effects of recombinant human interleukin-6 (rhIL-6) on hematopoiesis in eight healthy and nine irradiated cynomolgus monkeys. Of the healthy animals, three received rhIL-6 alone (10 micrograms/kg/d, subcutaneously [SC]), one received rhIL-6 in combination with rhIL-3 (10 micrograms/kg/d, SC), one received rhIL-6 in combination with recombinant cynomolgus granulocyte-macrophage colony-stimulating factor (rcGM-CSF; 10 micrograms/kg/d, SC), two received rhIL-6 in combination with recombinant human granulocyte-CSF (rhG-CSF; 10 micrograms/kg/d, SC), and one received rhIL-6 in combination with recombinant human leukemia inhibitory factor (rhLIF; 10 micrograms/kg/d, SC). All animals were treated for at least 2 weeks with rhIL-6 or the above mentioned combinations. rhIL-6 alone significantly increased the peripheral blood platelet counts (2- to 3.5-fold). The platelets reached a plateau between days 10 and 15 of treatment. No synergistic effects on platelet numbers were observed when rhIL-6 was combined with rhIL-3, rcGM-CSF, rhG-CSF, or rhLIF. In addition to rhIL-6, only rhLIF increased the platelet numbers when administered alone. To test whether rhIL-6 might also protect the animal from thrombocytopenia or shorten the time of thrombocytopenia after irradiation, we treated nine animals with total body irradiation (3.8 Gy). Six of the animals were additional treated with rhIL-6 (4 with 10 micrograms/kg/d; and 2 with 100 micrograms/kg/d) from day -1 or +1 to day 28 post irradiation. In these animals, rhIL-6 at the same dose effective in healthy animals (10 micrograms/kg/d) was not capable of protecting the animals from platelet nadir. However, when pegylated rhIL-6 was used at a dosage of 100 micrograms/kg/d post irradiation, the mean of the nadirs was 71,000/microL as compared with 39,000/microL in control animals and the time of thrombocytopenia was shorter (3 v 5 days). In all animals (healthy and irradiated), rhIL-6 did not increase the number of bone marrow megakaryocytes but induced a right shift of DNA ploidy in megakaryocytes. These data suggest that IL-6 acts as \"thrombopoietin\"-like activity, but not as \"megakaryocyte-CSF\"-like activity."} {"id": "PMID:1280478", "title": "Human arterial smooth muscle cells synthesize granulocyte colony-stimulating factor in response to interleukin-1 alpha and tumor necrosis factor-alpha.", "content": "Vascular smooth muscle cells (SMC) are a major cell type comprising the walls of blood vessels. We report the synthesis of granulocyte colony-stimulating factor (G-CSF) by cultured human SMC obtained from the internal mammary artery and thoracic aorta. Interleukin-1 alpha (IL-1 alpha) greatly increased in a dose-dependent manner the amount of this cytokine produced by the SMC, with tumor necrosis factor-alpha (TNF-alpha) being less effective. Newly formed G-CSF could be detected in culture supernatants within 6 hours after IL-1 alpha or TNF-alpha treatment. Northern blot analysis of SMC stimulated with IL-1 alpha and TNF-alpha showed an increase in the amount of mRNA for G-CSF as compared with control cells. Enhanced G-CSF mRNA levels were observed when SMC were treated with cycloheximide in the absence or presence of added cytokine. In vasculitis, the walls of blood vessels become inflamed as evidenced by a leucocytic infiltrate usually dominated by polymorphonuclear neutrophil leukocytes (PMNs). G-CSF is known to stimulate PMNs, and our findings raise the possibility that G-CSF made by SMC contributes to the development of vasculitis lesions.", "contents": "Human arterial smooth muscle cells synthesize granulocyte colony-stimulating factor in response to interleukin-1 alpha and tumor necrosis factor-alpha. Vascular smooth muscle cells (SMC) are a major cell type comprising the walls of blood vessels. We report the synthesis of granulocyte colony-stimulating factor (G-CSF) by cultured human SMC obtained from the internal mammary artery and thoracic aorta. Interleukin-1 alpha (IL-1 alpha) greatly increased in a dose-dependent manner the amount of this cytokine produced by the SMC, with tumor necrosis factor-alpha (TNF-alpha) being less effective. Newly formed G-CSF could be detected in culture supernatants within 6 hours after IL-1 alpha or TNF-alpha treatment. Northern blot analysis of SMC stimulated with IL-1 alpha and TNF-alpha showed an increase in the amount of mRNA for G-CSF as compared with control cells. Enhanced G-CSF mRNA levels were observed when SMC were treated with cycloheximide in the absence or presence of added cytokine. In vasculitis, the walls of blood vessels become inflamed as evidenced by a leucocytic infiltrate usually dominated by polymorphonuclear neutrophil leukocytes (PMNs). G-CSF is known to stimulate PMNs, and our findings raise the possibility that G-CSF made by SMC contributes to the development of vasculitis lesions."} {"id": "PMID:1280479", "title": "G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic leukemia cells by activated CD3 antigen-positive cytotoxic T cells.", "content": "A highly purified, 300-Kd bispecific monoclonal antibody (MoAb) heteroconjugate was prepared by covalently linking the anti-CD3 MoAb, G19.4, to the anti-CD19 MoAb, B43. Dual-color staining techniques and multiparameter flow cytometry confirmed that this alpha CD3 x alpha CD19 heteroconjugate was able to bind to both CD3+ T cells and CD19+ t(4;11) acute lymphoblastic leukemia (ALL) cells. T-cell-mediated lysis of freshly isolated primary bone marrow blasts from nine newly diagnosed ALL patients with a t(4;11)(q21;q23) chromosomal translocation were studied with 51Cr-release assays. Picomolar concentrations of alpha CD3 x alpha CD19 MoAb heteroconjugate effectively triggered lysis of CD19+ t(4;11) ALL cells by interleukin-2-activated CD3+ peripheral blood T-cell (PBTC) effectors but did not augment the cytolytic activity of the same effectors against CD19- T-ALL cells. In contrast to the alpha CD3 x alpha CD19 heteroconjugate, neither the alpha CD3 x alpha CD3 homoconjugate control nor the alpha CD19 x alpha CD72 heteroconjugate control facilitated the cytolysis of t(4;11) ALL blasts. Occupation of the target CD19 binding sites on t(4;11) ALL blasts by preincubation with excess unconjugated alpha CD19 MoAb abrogated the potentiating effects of the alpha CD3 x alpha CD19 heteroconjugate on PBTC-mediated cytolysis. Thus, the cell type-specific cytolysis of t(4;11) ALL blasts by PBTC effectors is dependent on both the alpha CD19 and alpha CD3 moieties of the alpha CD3 x alpha CD19 heteroconjugate. To our knowledge, this is the first description of an effective bispecific antibody that facilitates the T-cell-mediated lysis of t(4;11) ALL blasts.", "contents": "G19.4(alpha CD3) x B43(alpha CD19) monoclonal antibody heteroconjugate triggers CD19 antigen-specific lysis of t(4;11) acute lymphoblastic leukemia cells by activated CD3 antigen-positive cytotoxic T cells. A highly purified, 300-Kd bispecific monoclonal antibody (MoAb) heteroconjugate was prepared by covalently linking the anti-CD3 MoAb, G19.4, to the anti-CD19 MoAb, B43. Dual-color staining techniques and multiparameter flow cytometry confirmed that this alpha CD3 x alpha CD19 heteroconjugate was able to bind to both CD3+ T cells and CD19+ t(4;11) acute lymphoblastic leukemia (ALL) cells. T-cell-mediated lysis of freshly isolated primary bone marrow blasts from nine newly diagnosed ALL patients with a t(4;11)(q21;q23) chromosomal translocation were studied with 51Cr-release assays. Picomolar concentrations of alpha CD3 x alpha CD19 MoAb heteroconjugate effectively triggered lysis of CD19+ t(4;11) ALL cells by interleukin-2-activated CD3+ peripheral blood T-cell (PBTC) effectors but did not augment the cytolytic activity of the same effectors against CD19- T-ALL cells. In contrast to the alpha CD3 x alpha CD19 heteroconjugate, neither the alpha CD3 x alpha CD3 homoconjugate control nor the alpha CD19 x alpha CD72 heteroconjugate control facilitated the cytolysis of t(4;11) ALL blasts. Occupation of the target CD19 binding sites on t(4;11) ALL blasts by preincubation with excess unconjugated alpha CD19 MoAb abrogated the potentiating effects of the alpha CD3 x alpha CD19 heteroconjugate on PBTC-mediated cytolysis. Thus, the cell type-specific cytolysis of t(4;11) ALL blasts by PBTC effectors is dependent on both the alpha CD19 and alpha CD3 moieties of the alpha CD3 x alpha CD19 heteroconjugate. To our knowledge, this is the first description of an effective bispecific antibody that facilitates the T-cell-mediated lysis of t(4;11) ALL blasts."} {"id": "PMID:1280480", "title": "Human peritoneal mesothelial cells produce many cytokines (granulocyte colony-stimulating factor [CSF], granulocyte-monocyte-CSF, macrophage-CSF, interleukin-1 [IL-1], and IL-6) and are activated and stimulated to grow by IL-1.", "content": "To investigate the role of peritoneal mesothelial cells in regulating hematopoiesis, as well as inflammation, healing, and tissue regeneration processes, long-term cultures of peritoneal mesothelial cells from human endocavitarian fluids were established. The purity of the cell population was assessed by morphologic and immunocytochemical criteria. Five peritoneal mesothelial cell cultures were analyzed for cytokine expression. Macrophage colony-stimulating factor (M-CSF), granulocyte-CSF (G-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-6 transcripts were constantly but variably detected throughout the culture period, while granulocyte-monocyte-CSF (GM-CSF) expression started as the cell culture aged. No IL-2, IL-3, IL-4, IL-5, or IL-7 transcripts were detected in the same samples. Corresponding cytokine activities were detected in the supernatants of the cultures. Peritoneal mesothelial cells proliferated after the addition of exogenous IL-1 beta or IL-1 alpha, whereas the addition of recombinant GM-CSF, G-CSF, M-CSF, or IL-6 failed to trigger proliferation. IL-1 receptor type I transcripts were detected in peritoneal mesothelial cells. Moreover, IL-1 was able to upregulate the expression of the genes that code for G-CSF, GM-CSF, IL-1 alpha, and IL-1 beta in these cells. These data indicate that peritoneal mesothelial cells produce many cytokines and suggest that IL-1 is a regulatory molecule for peritoneal mesothelial cells.", "contents": "Human peritoneal mesothelial cells produce many cytokines (granulocyte colony-stimulating factor [CSF], granulocyte-monocyte-CSF, macrophage-CSF, interleukin-1 [IL-1], and IL-6) and are activated and stimulated to grow by IL-1. To investigate the role of peritoneal mesothelial cells in regulating hematopoiesis, as well as inflammation, healing, and tissue regeneration processes, long-term cultures of peritoneal mesothelial cells from human endocavitarian fluids were established. The purity of the cell population was assessed by morphologic and immunocytochemical criteria. Five peritoneal mesothelial cell cultures were analyzed for cytokine expression. Macrophage colony-stimulating factor (M-CSF), granulocyte-CSF (G-CSF), interleukin-1 alpha (IL-1 alpha), IL-1 beta, and IL-6 transcripts were constantly but variably detected throughout the culture period, while granulocyte-monocyte-CSF (GM-CSF) expression started as the cell culture aged. No IL-2, IL-3, IL-4, IL-5, or IL-7 transcripts were detected in the same samples. Corresponding cytokine activities were detected in the supernatants of the cultures. Peritoneal mesothelial cells proliferated after the addition of exogenous IL-1 beta or IL-1 alpha, whereas the addition of recombinant GM-CSF, G-CSF, M-CSF, or IL-6 failed to trigger proliferation. IL-1 receptor type I transcripts were detected in peritoneal mesothelial cells. Moreover, IL-1 was able to upregulate the expression of the genes that code for G-CSF, GM-CSF, IL-1 alpha, and IL-1 beta in these cells. These data indicate that peritoneal mesothelial cells produce many cytokines and suggest that IL-1 is a regulatory molecule for peritoneal mesothelial cells."} {"id": "PMID:1280481", "title": "Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor is caused by inhibition of programmed cell death.", "content": "In the absence of appropriate stimuli, polymorphonuclear neutrophils (PMN) undergo programmed cell death (PCD), also termed apoptosis. We show that granulocyte-macrophage colony-stimulating factor (GM-CSF), but not the chemotactic factors formyl-methionyl-leucyl-phenylalanine (FMLP), recombinant human (rh) C5a, transforming growth factor (TGF)-beta, and interleukin-8 (IL-8), or other cytokines including IL-3, IL-4, IL-6, and G-CSF, maintains viability of PMN in culture by preventing these cells from undergoing PCD. Prevention from PCD by GM-CSF was associated with induction of RNA and protein synthesis in PMN. Inhibition of RNA and protein synthesis by actinomycin-D and cycloheximide impeded the protection of apoptosis by GM-CSF. Similarly, neutralization of GM-CSF biologic activity by a specific antiserum abrogated GM-CSF-mediated inhibition of PCD.", "contents": "Prolongation of survival of human polymorphonuclear neutrophils by granulocyte-macrophage colony-stimulating factor is caused by inhibition of programmed cell death. In the absence of appropriate stimuli, polymorphonuclear neutrophils (PMN) undergo programmed cell death (PCD), also termed apoptosis. We show that granulocyte-macrophage colony-stimulating factor (GM-CSF), but not the chemotactic factors formyl-methionyl-leucyl-phenylalanine (FMLP), recombinant human (rh) C5a, transforming growth factor (TGF)-beta, and interleukin-8 (IL-8), or other cytokines including IL-3, IL-4, IL-6, and G-CSF, maintains viability of PMN in culture by preventing these cells from undergoing PCD. Prevention from PCD by GM-CSF was associated with induction of RNA and protein synthesis in PMN. Inhibition of RNA and protein synthesis by actinomycin-D and cycloheximide impeded the protection of apoptosis by GM-CSF. Similarly, neutralization of GM-CSF biologic activity by a specific antiserum abrogated GM-CSF-mediated inhibition of PCD."} {"id": "PMID:1280484", "title": "A simple method for hemoglobin measurement in cell culture system.", "content": "A simple method of hemoglobin analysis in a cell culture system is described. Hemoglobins synthesized in cell cultures are labeled with radioactive amino acids. The cell extract containing radiolabeled hemoglobin is mixed with A, F, S, C, hemoglobin markers and separated by cellulose acetate electrophoresis. Individual bands of hemoglobin are cut from the gel and analyzed for radioactivity. This method is especially useful for determination of newly synthesized minute amount of hemoglobin in cell extracts that are difficult to visualize by staining procedure.", "contents": "A simple method for hemoglobin measurement in cell culture system. A simple method of hemoglobin analysis in a cell culture system is described. Hemoglobins synthesized in cell cultures are labeled with radioactive amino acids. The cell extract containing radiolabeled hemoglobin is mixed with A, F, S, C, hemoglobin markers and separated by cellulose acetate electrophoresis. Individual bands of hemoglobin are cut from the gel and analyzed for radioactivity. This method is especially useful for determination of newly synthesized minute amount of hemoglobin in cell extracts that are difficult to visualize by staining procedure."} {"id": "PMID:1280485", "title": "Role of tachykinins in the control of pancreatic secretion and circulation.", "content": "Tachykinins (TK) are family of peptides including substance P (SP), substance K (SK) and neuromedin K (NK) that have been found in the nerves of the gastrointestinal tract and proposed to act as neurotransmitters to affect the motor, secretory and circulatory functions of the gut, but little is known about their action on the pancreas. In this study three series of tests were carried out to determine the action of SP, SK and NK on pancreatic secretion in conscious dogs and amylase release from the dispersed rat pancreatic acini and to correlate the alterations in pancreatic secretory and circulatory effects of TK in anesthetized dogs. SP, SK and NK infused i.v. in graded doses (0.12-1.0 microgram/kg per h) in conscious dogs stimulated pancreatic protein outputs reaching, respectively, 38% and 23% of the maximal response to CCK (40 pmol/kg per h). HCO3- outputs were also significantly increased but the highest response did not exceed about 5% of secretin (328 pmol/kg per h) maximum. Cholinergic blockade by atropine abolished the pancreatic responses to tachykinins. When added at various concentrations (10(-11)-10(-7) M) to the incubation medium of rat dispersed pancreatic acini, SK, SP and NK increased in concentration-dependent manner the release of amylase from the resting pancreatic acini and augmented the enzyme release induced by CCK-8 and by urecholine. In anesthetized dogs infused with a background dose of secretin (82 pmol/kg per h), addition of SP, SK and NK caused an immediate and dose-dependent increase in the pancreatic blood flow, oxygen consumption and pancreatic secretion accompanied by a dose-dependent decrease in arterial blood pressure. This study shows that TK are potent pancreatic circulatory stimulants and moderate secretagogues both in vivo and in vitro, acting, at least in part, via cholinergic pathway.", "contents": "Role of tachykinins in the control of pancreatic secretion and circulation. Tachykinins (TK) are family of peptides including substance P (SP), substance K (SK) and neuromedin K (NK) that have been found in the nerves of the gastrointestinal tract and proposed to act as neurotransmitters to affect the motor, secretory and circulatory functions of the gut, but little is known about their action on the pancreas. In this study three series of tests were carried out to determine the action of SP, SK and NK on pancreatic secretion in conscious dogs and amylase release from the dispersed rat pancreatic acini and to correlate the alterations in pancreatic secretory and circulatory effects of TK in anesthetized dogs. SP, SK and NK infused i.v. in graded doses (0.12-1.0 microgram/kg per h) in conscious dogs stimulated pancreatic protein outputs reaching, respectively, 38% and 23% of the maximal response to CCK (40 pmol/kg per h). HCO3- outputs were also significantly increased but the highest response did not exceed about 5% of secretin (328 pmol/kg per h) maximum. Cholinergic blockade by atropine abolished the pancreatic responses to tachykinins. When added at various concentrations (10(-11)-10(-7) M) to the incubation medium of rat dispersed pancreatic acini, SK, SP and NK increased in concentration-dependent manner the release of amylase from the resting pancreatic acini and augmented the enzyme release induced by CCK-8 and by urecholine. In anesthetized dogs infused with a background dose of secretin (82 pmol/kg per h), addition of SP, SK and NK caused an immediate and dose-dependent increase in the pancreatic blood flow, oxygen consumption and pancreatic secretion accompanied by a dose-dependent decrease in arterial blood pressure. This study shows that TK are potent pancreatic circulatory stimulants and moderate secretagogues both in vivo and in vitro, acting, at least in part, via cholinergic pathway."} {"id": "PMID:1280486", "title": "Occurrence of ovulation after intracerebroventricular infusion of substance P in 6-OHDA pretreated female rats.", "content": "Substance P (SP) infused into the third cerebral ventricle blocks spontaneous ovulation in female rats, probably through catecholaminergic neurons. The studies presented in this paper were undertaken to investigate whether SP exerts its suppressing effect on ovulation in 6-hydroxydopamine (6-OHDA) pretreated female rats. After 8-12 days following 6-OHDA pretreatment female rats were infused, on the day of proestrus, with vehicle and all animals were found to ovulate or with a solution containing 5 nmol of SP and 89% of female rats were then found to ovulate. In the group pretreated with vehicle and subsequently infused with SP, ovulation was found to occur only in 25% of animals. The obtained results indicate that spontaneous ovulation in 6-OHDA-pretreated female rats cannot be blocked by i.c.v. administration of SP, and it may be concluded that SP exerts its suppressing effect through the monoaminergic neurons.", "contents": "Occurrence of ovulation after intracerebroventricular infusion of substance P in 6-OHDA pretreated female rats. Substance P (SP) infused into the third cerebral ventricle blocks spontaneous ovulation in female rats, probably through catecholaminergic neurons. The studies presented in this paper were undertaken to investigate whether SP exerts its suppressing effect on ovulation in 6-hydroxydopamine (6-OHDA) pretreated female rats. After 8-12 days following 6-OHDA pretreatment female rats were infused, on the day of proestrus, with vehicle and all animals were found to ovulate or with a solution containing 5 nmol of SP and 89% of female rats were then found to ovulate. In the group pretreated with vehicle and subsequently infused with SP, ovulation was found to occur only in 25% of animals. The obtained results indicate that spontaneous ovulation in 6-OHDA-pretreated female rats cannot be blocked by i.c.v. administration of SP, and it may be concluded that SP exerts its suppressing effect through the monoaminergic neurons."} {"id": "PMID:1280487", "title": "Influence of suramin on some DNA-directed enzymes and primary cultures of chicken embryo and rat cells.", "content": "The influence of suramin on O6-alkylguanine-DNA alkyltransferase (AT), DNase I and poly(adenosine diphosphate ribose)polymerase (PADPR) as well as on primary cultures of rat and chick embryo cells was examined by using some short-term tests. AT and DNase I were inhibited by suramin in a dose-dependent manner (DE50 = 65 and 100 micrograms/ml, respectively). PADPR activity was increased over a concentration range of 40-320 micrograms/ml. At concentrations above 40 micrograms/ml suramin decreased scheduled and unscheduled DNA synthesis. At doses of below 20 micrograms/ml the substance slightly stimulated unscheduled DNA synthesis in embryonic cells. Suramin enhanced nucleoid sedimentation and diminished the viscosity of alkaline cell lysates. From the present results it is concluded that suramin, at clinically relevant concentrations, is able to interact with enzyme systems which are critical to important nuclear functions and to interfere--in a cell specific manner--with histones and/or matrix proteins, resulting in greater chromatin compactness.", "contents": "Influence of suramin on some DNA-directed enzymes and primary cultures of chicken embryo and rat cells. The influence of suramin on O6-alkylguanine-DNA alkyltransferase (AT), DNase I and poly(adenosine diphosphate ribose)polymerase (PADPR) as well as on primary cultures of rat and chick embryo cells was examined by using some short-term tests. AT and DNase I were inhibited by suramin in a dose-dependent manner (DE50 = 65 and 100 micrograms/ml, respectively). PADPR activity was increased over a concentration range of 40-320 micrograms/ml. At concentrations above 40 micrograms/ml suramin decreased scheduled and unscheduled DNA synthesis. At doses of below 20 micrograms/ml the substance slightly stimulated unscheduled DNA synthesis in embryonic cells. Suramin enhanced nucleoid sedimentation and diminished the viscosity of alkaline cell lysates. From the present results it is concluded that suramin, at clinically relevant concentrations, is able to interact with enzyme systems which are critical to important nuclear functions and to interfere--in a cell specific manner--with histones and/or matrix proteins, resulting in greater chromatin compactness."} {"id": "PMID:1280490", "title": "The level of serum granulocyte colony-stimulating factor in cancer patients with leukocytosis.", "content": "The level of serum granulocyte colony-stimulating factor (G-CSF) obtained from patients with leukocytosis (greater than 10,000/microliters) between May 1989 and April 1991 was measured by enzyme immunoassay. Studied were 18 patients with malignant neoplasms (median age, 64 years) and 14 patients with hematologic disease (median age, 59 years). Increased serum G-CSF values ranging from 70 to 374 pg/ml were noted in 7 of 15 lung cancer cases, a case of malignant thymoma and a blastic crisis of chronic myelogenous leukemia. The rest of the cases showed a normal value (less than 60 pg/ml). There was no correlation between the neutrophil count and G-CSF level. In lung cancer cases with high G-CSF values, neither a characteristic histologic type nor common elevation of tumor markers could be seen. The neutrophil alkaline phosphatase score was significantly increased and hypercalcemia was presented in high G-CSF cases. G-CSF may contribute at least in part to unknown leukocytosis observed in malignant neoplasms, especially in lung cancer.", "contents": "The level of serum granulocyte colony-stimulating factor in cancer patients with leukocytosis. The level of serum granulocyte colony-stimulating factor (G-CSF) obtained from patients with leukocytosis (greater than 10,000/microliters) between May 1989 and April 1991 was measured by enzyme immunoassay. Studied were 18 patients with malignant neoplasms (median age, 64 years) and 14 patients with hematologic disease (median age, 59 years). Increased serum G-CSF values ranging from 70 to 374 pg/ml were noted in 7 of 15 lung cancer cases, a case of malignant thymoma and a blastic crisis of chronic myelogenous leukemia. The rest of the cases showed a normal value (less than 60 pg/ml). There was no correlation between the neutrophil count and G-CSF level. In lung cancer cases with high G-CSF values, neither a characteristic histologic type nor common elevation of tumor markers could be seen. The neutrophil alkaline phosphatase score was significantly increased and hypercalcemia was presented in high G-CSF cases. G-CSF may contribute at least in part to unknown leukocytosis observed in malignant neoplasms, especially in lung cancer."} {"id": "PMID:1280491", "title": "Hypersensitivity pneumonitis induced by hexamethylene diisocyanate.", "content": "A case of hypersensitivity pneumonitis (HP) induced by hexamethylene diisocyanate (HDI) is described. Serial determinations of the lymphocyte surface phenotypes by two-color assay revealed the following: 1) increased activated cytotoxic T lymphocytes in the bronchoalveolar lavage fluid (BALF), and 2) increased percentage and absolute number of non-major histocompatibility complex (MHC)-restricted natural killer (NK) cells in the peripheral blood (PB) during the recovery phase of the disease. These findings were considered to be related to the activity of the disease.", "contents": "Hypersensitivity pneumonitis induced by hexamethylene diisocyanate. A case of hypersensitivity pneumonitis (HP) induced by hexamethylene diisocyanate (HDI) is described. Serial determinations of the lymphocyte surface phenotypes by two-color assay revealed the following: 1) increased activated cytotoxic T lymphocytes in the bronchoalveolar lavage fluid (BALF), and 2) increased percentage and absolute number of non-major histocompatibility complex (MHC)-restricted natural killer (NK) cells in the peripheral blood (PB) during the recovery phase of the disease. These findings were considered to be related to the activity of the disease."} {"id": "PMID:1280488", "title": "New polymer alloy dialysis membranes with varying permeabilities and sievings.", "content": "The superstructure of polymer alloys that is responsible for their function is best controlled by varying the polymers, polymer blend ratio, solvents, temperature, or all four. Dialysis membranes made of polymer alloys can have varying pure water and solute permeabilities, pore sizes, pore size distributions, and mechanical strengths when wet. Resistance to heat and mass transfer can also vary. The optimal superstructure design of a polymer alloy dialysis membrane enables it to remove efficiently newly identified uremic toxins with higher molecular weights from patients on hemodialysis. The authors prepared new hollow fiber dialysis membranes using a polyethersulfone/polyacrylate (PEPA) polymer alloy, and evaluated pure water and solute permeabilities and reflection coefficients that are dependent upon the superstructure of the PEPA membranes. The new PEPA membranes are asymmetric, with skin layers on either side. The values for pure water permeability and overall mass transfer coefficients for urea, creatinine, and vitamin B12 are quite adequate for hemodialysis. The reflection coefficients for substances with molecular weights greater than 3,000 are strongly dependent upon the conditions under which the membranes were prepared. The values for cytochrome C permeability ranged from 0.42 to 0.71 microns/s.", "contents": "New polymer alloy dialysis membranes with varying permeabilities and sievings. The superstructure of polymer alloys that is responsible for their function is best controlled by varying the polymers, polymer blend ratio, solvents, temperature, or all four. Dialysis membranes made of polymer alloys can have varying pure water and solute permeabilities, pore sizes, pore size distributions, and mechanical strengths when wet. Resistance to heat and mass transfer can also vary. The optimal superstructure design of a polymer alloy dialysis membrane enables it to remove efficiently newly identified uremic toxins with higher molecular weights from patients on hemodialysis. The authors prepared new hollow fiber dialysis membranes using a polyethersulfone/polyacrylate (PEPA) polymer alloy, and evaluated pure water and solute permeabilities and reflection coefficients that are dependent upon the superstructure of the PEPA membranes. The new PEPA membranes are asymmetric, with skin layers on either side. The values for pure water permeability and overall mass transfer coefficients for urea, creatinine, and vitamin B12 are quite adequate for hemodialysis. The reflection coefficients for substances with molecular weights greater than 3,000 are strongly dependent upon the conditions under which the membranes were prepared. The values for cytochrome C permeability ranged from 0.42 to 0.71 microns/s."} {"id": "PMID:1280494", "title": "Assessing and counteracting the prooxidant effects of anticancer drugs.", "content": "The relationship between peroxide generation and respective cellular damage, triggering various biochemical consequences is first discussed. Then we review the prooxidant effects of various anticancer drugs including anthracyclines and bleomycin, platinum derivatives and the N- and S-mustards. We present and discuss some experimental results on peroxidase inhibition by drugs such as zinc salts, almitrine, deferoxamine, which had previously been tested as efficient in vivo treatment on chlormethine intoxication. In an overview we propose that not only ionizing radiations and anticancer drugs, but also promoters and initiators of cancer might all generate free radicals, in turn triggering oxidative processes generating endogenous peroxides, then probably amplifying the deleterious biological response. The possible limitations of drug therapies decreasing peroxide generation are presented.", "contents": "Assessing and counteracting the prooxidant effects of anticancer drugs. The relationship between peroxide generation and respective cellular damage, triggering various biochemical consequences is first discussed. Then we review the prooxidant effects of various anticancer drugs including anthracyclines and bleomycin, platinum derivatives and the N- and S-mustards. We present and discuss some experimental results on peroxidase inhibition by drugs such as zinc salts, almitrine, deferoxamine, which had previously been tested as efficient in vivo treatment on chlormethine intoxication. In an overview we propose that not only ionizing radiations and anticancer drugs, but also promoters and initiators of cancer might all generate free radicals, in turn triggering oxidative processes generating endogenous peroxides, then probably amplifying the deleterious biological response. The possible limitations of drug therapies decreasing peroxide generation are presented."} {"id": "PMID:1280492", "title": "Peptides reactive with a transmission-blocking monoclonal antibody against Plasmodium falciparum Pfs25: 2000-fold affinity increase by PEPSCAN-based amino acid substitutions.", "content": "Based on PEPSCAN analyses, a peptide derived from the 25-kDa surface protein of P. falciparum sexual stages (LDTSNPVKT, amino acids 122-130) was recently shown to react with transmission-blocking monoclonal antibodies. Subsequently, a pinbound construct (FDDTDPIKK; six amino acids substituted) was designed that reacted 1000 times better with the transmission-blocking monoclonal antibody 32F81 than with the parent LDTSNPVKT peptide. While this construct was obtained through single amino acid replacement studies, it now is shown that the combined contribution of the various substitutions is necessary to give the total effect. Free peptides comprising LDTSNPVKT or FDDTDPIKK were shown to inhibit the interaction of the transmission-blocking monoclonal antibody with plate-bound peptides, when prepared by conventional synthesis procedures. Compared with peptides that contained LDTSNPVKT, similar levels of inhibition could be achieved with an average 500-fold lower molar amount of peptides containing the FDDTDPIKK sequence. Affinity constants of the peptides for the transmission-blocking monoclonal antibody ranged from 1.3 x 10(5), for peptides that contained LDTSNPVKT, to 2.6 x 10(8), for peptides that contained FDDTDPIKK. The structural relationship between the epitope of the 25-kDa surface protein and the peptides was demonstrated by competition experiments with the transmission-blocking monoclonal antibody 32F81. Again, peptides comprising the newly designed sequence FDDTDPIKK competed about 200 times better than peptides with the parent LDTSNPVKT sequence.", "contents": "Peptides reactive with a transmission-blocking monoclonal antibody against Plasmodium falciparum Pfs25: 2000-fold affinity increase by PEPSCAN-based amino acid substitutions. Based on PEPSCAN analyses, a peptide derived from the 25-kDa surface protein of P. falciparum sexual stages (LDTSNPVKT, amino acids 122-130) was recently shown to react with transmission-blocking monoclonal antibodies. Subsequently, a pinbound construct (FDDTDPIKK; six amino acids substituted) was designed that reacted 1000 times better with the transmission-blocking monoclonal antibody 32F81 than with the parent LDTSNPVKT peptide. While this construct was obtained through single amino acid replacement studies, it now is shown that the combined contribution of the various substitutions is necessary to give the total effect. Free peptides comprising LDTSNPVKT or FDDTDPIKK were shown to inhibit the interaction of the transmission-blocking monoclonal antibody with plate-bound peptides, when prepared by conventional synthesis procedures. Compared with peptides that contained LDTSNPVKT, similar levels of inhibition could be achieved with an average 500-fold lower molar amount of peptides containing the FDDTDPIKK sequence. Affinity constants of the peptides for the transmission-blocking monoclonal antibody ranged from 1.3 x 10(5), for peptides that contained LDTSNPVKT, to 2.6 x 10(8), for peptides that contained FDDTDPIKK. The structural relationship between the epitope of the 25-kDa surface protein and the peptides was demonstrated by competition experiments with the transmission-blocking monoclonal antibody 32F81. Again, peptides comprising the newly designed sequence FDDTDPIKK competed about 200 times better than peptides with the parent LDTSNPVKT sequence."} {"id": "PMID:1280495", "title": "Evaluation of soluble CD 14 and neopterin as serum parameters of the inflammatory activity of pulmonary sarcoidosis.", "content": "CD14 represents the most specific marker for monocytes/macrophages. It has been demonstrated in vitro that monocytes/macrophages lose this antigen upon activation. Results of studies investigating the expression of membrane-bound CD14 on the surface of monocytes/macrophages in sarcoidosis patients are controversial. To investigate whether the soluble form of CD14 reflects monocyte/macrophage activation in sarcoidosis, serum levels of soluble CD14 were determined concurrently with other serum markers of monocyte/macrophage activation (neopterin, angiotensin-converting enzyme) in 50 consecutive patients with bioptically confirmed sarcoidosis. The patients were allocated to three groups according to disease activity and therapy. The soluble interleukin-2 receptor in serum and the CD4/CD8 ratio in lavage fluid were used to monitor T-lymphocyte activation. No significant differences in serum or bronchoalveolar lavage levels of soluble CD14 were observed in patients with active or inactive sarcoidosis. Despite the presence of normal soluble CD14 serum concentrations a correlation with serum neopterin and angiotensin-converting enzyme was found in active sarcoidosis (soluble CD14 versus neopterin, rs = 0.61 and 0.65, P < 0.05 and 0.01, respectively; soluble CD14 versus angiotensin-converting enzyme, rs = 0.6 and 0.72, P < 0.02 and 0.003, respectively). A correlation between soluble CD14 and parameters of T-cell activity was not demonstrated. We therefore conclude that soluble CD14 in serum is not a useful clinical parameter in establishing disease activity in sarcoidosis. Neopterin and angiotensin-converting enzyme serum concentrations are parameters with higher sensitivity, although specificity remains very low. The exact role of CD14 antigen in sarcoidosis requires further investigation.", "contents": "Evaluation of soluble CD 14 and neopterin as serum parameters of the inflammatory activity of pulmonary sarcoidosis. CD14 represents the most specific marker for monocytes/macrophages. It has been demonstrated in vitro that monocytes/macrophages lose this antigen upon activation. Results of studies investigating the expression of membrane-bound CD14 on the surface of monocytes/macrophages in sarcoidosis patients are controversial. To investigate whether the soluble form of CD14 reflects monocyte/macrophage activation in sarcoidosis, serum levels of soluble CD14 were determined concurrently with other serum markers of monocyte/macrophage activation (neopterin, angiotensin-converting enzyme) in 50 consecutive patients with bioptically confirmed sarcoidosis. The patients were allocated to three groups according to disease activity and therapy. The soluble interleukin-2 receptor in serum and the CD4/CD8 ratio in lavage fluid were used to monitor T-lymphocyte activation. No significant differences in serum or bronchoalveolar lavage levels of soluble CD14 were observed in patients with active or inactive sarcoidosis. Despite the presence of normal soluble CD14 serum concentrations a correlation with serum neopterin and angiotensin-converting enzyme was found in active sarcoidosis (soluble CD14 versus neopterin, rs = 0.61 and 0.65, P < 0.05 and 0.01, respectively; soluble CD14 versus angiotensin-converting enzyme, rs = 0.6 and 0.72, P < 0.02 and 0.003, respectively). A correlation between soluble CD14 and parameters of T-cell activity was not demonstrated. We therefore conclude that soluble CD14 in serum is not a useful clinical parameter in establishing disease activity in sarcoidosis. Neopterin and angiotensin-converting enzyme serum concentrations are parameters with higher sensitivity, although specificity remains very low. The exact role of CD14 antigen in sarcoidosis requires further investigation."} {"id": "PMID:1280493", "title": "Multiple peptide synthesis on polypropylene membranes for rapid screening of bioactive peptides.", "content": "A new multiple peptide synthesis technique that allows several hundred peptides to be synthesized on polypropylene membranes in one working day has been developed. Peptides are assembled as spots on a membrane sheet sandwiched between two 96-reaction well templates. Activity measurements can be made either with the membrane-bound peptides, for example, using an enzyme linked immunosorbent assay (ELISA), or after cleavage from the membrane. The method is simple and economical in the use of reagents, and peptides are of high quality, making possible the synthesis of rather long (> 20 residues) peptides. This method has been used to identify antigenic determinants recognized by antisera to bovine myelin proteolipid protein.", "contents": "Multiple peptide synthesis on polypropylene membranes for rapid screening of bioactive peptides. A new multiple peptide synthesis technique that allows several hundred peptides to be synthesized on polypropylene membranes in one working day has been developed. Peptides are assembled as spots on a membrane sheet sandwiched between two 96-reaction well templates. Activity measurements can be made either with the membrane-bound peptides, for example, using an enzyme linked immunosorbent assay (ELISA), or after cleavage from the membrane. The method is simple and economical in the use of reagents, and peptides are of high quality, making possible the synthesis of rather long (> 20 residues) peptides. This method has been used to identify antigenic determinants recognized by antisera to bovine myelin proteolipid protein."} {"id": "PMID:1280496", "title": "Granulocyte colony-stimulating factor treatment in AIDS patients.", "content": "Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/microliters), who were treated concomitantly with recombinant human G-CSF (3-4 micrograms subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted.", "contents": "Granulocyte colony-stimulating factor treatment in AIDS patients. Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia (< 750 cells/microliters), who were treated concomitantly with recombinant human G-CSF (3-4 micrograms subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Life-threatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted."} {"id": "PMID:1280497", "title": "Expression of GD2-epitopes in human intracranial tumors and normal brain.", "content": "Two monoclonal antibodies (mabs) were raised against ganglioside GD2 (Gtri2) and tested on human intracranial tumors and normal brain by immunohistochemical methods both in frozen and paraffin embedded sections. In normal brain structures, astrocytes were visualized with both mabs (BW 625 and BW 704) almost exclusively in the subventricular and subpial layer. A minor amount of myelin sheaths in well defined localisation was only recognized in frozen sections. Consequently in astrocytic tumors of different grades of malignancy (WHO I-IV), astrocytes were depicted in their characteristic shape and arrangement around vessels. In addition, staining was observed in meningiomas and schwannomas, but not in pituitary adenomas or metastatic carcinomas. In meningioma und schwannoma the staining was restricted to the cellular periphery and was again present in frozen section material and absent in paraffin embedded tissue. In astrocytes, reactive and neoplastic, obviously fibrous processes and cytoplasm were distinctly stained both in frozen and paraffin embedded sections. It is concluded that some neuroectodermal derived cells as well as myelin of defined localisation express GD2 on the membrane surfaces and in the cytoplasm. The latter may primarily be the case in fibrous astrocytes, which were stained in reactive and pathologic conditions. The reaction can be used as diagnostic tool in astrocytic tumors; its positive therapeutic significance is hampered by the fact that (1) not all cells in heterogeneous tumor populations express the epitope and (2) there are normal structures which do so.", "contents": "Expression of GD2-epitopes in human intracranial tumors and normal brain. Two monoclonal antibodies (mabs) were raised against ganglioside GD2 (Gtri2) and tested on human intracranial tumors and normal brain by immunohistochemical methods both in frozen and paraffin embedded sections. In normal brain structures, astrocytes were visualized with both mabs (BW 625 and BW 704) almost exclusively in the subventricular and subpial layer. A minor amount of myelin sheaths in well defined localisation was only recognized in frozen sections. Consequently in astrocytic tumors of different grades of malignancy (WHO I-IV), astrocytes were depicted in their characteristic shape and arrangement around vessels. In addition, staining was observed in meningiomas and schwannomas, but not in pituitary adenomas or metastatic carcinomas. In meningioma und schwannoma the staining was restricted to the cellular periphery and was again present in frozen section material and absent in paraffin embedded tissue. In astrocytes, reactive and neoplastic, obviously fibrous processes and cytoplasm were distinctly stained both in frozen and paraffin embedded sections. It is concluded that some neuroectodermal derived cells as well as myelin of defined localisation express GD2 on the membrane surfaces and in the cytoplasm. The latter may primarily be the case in fibrous astrocytes, which were stained in reactive and pathologic conditions. The reaction can be used as diagnostic tool in astrocytic tumors; its positive therapeutic significance is hampered by the fact that (1) not all cells in heterogeneous tumor populations express the epitope and (2) there are normal structures which do so."} {"id": "PMID:1280498", "title": "Rat lymphoid cell--derived histamine and 5-hydroxytryptamine releasing factor.", "content": "The in vitro production of histamine releasing factor (HRF) by lymphoid cells of rats, both normal and infected with Nippostrongylus brasiliensis, has been studied. Spleen cells and thymocytes were cultured either alone or in the presence of mitogen (PHA, 10 and 50 micrograms/ml) and the dialysed cell-free supernatants were tested for histamine releasing activity on rat peritoneal and pleural mast cell in vitro. We found that spleen cells and thymocytes of normal rats stimulated with PHA in 24 h cultures generated a factor which released histamine and 5-hydroxytryptamine from mast cells, and this ability was potentiated following N. brasiliensis infection of rats - lymphoid cells donors. Pleural mast cells were more sensitive to the action of HRF than peritoneal cells. Rat HRF had an apparent m.w. of 50,000 to 70,000 daltons as determined by gel chromatography and was a heat stable protein inducing histamine release from homologous mast cells in a very rapid (complete in 1-2 min at 37 degrees C), dose and temperature dependent secretory process.", "contents": "Rat lymphoid cell--derived histamine and 5-hydroxytryptamine releasing factor. The in vitro production of histamine releasing factor (HRF) by lymphoid cells of rats, both normal and infected with Nippostrongylus brasiliensis, has been studied. Spleen cells and thymocytes were cultured either alone or in the presence of mitogen (PHA, 10 and 50 micrograms/ml) and the dialysed cell-free supernatants were tested for histamine releasing activity on rat peritoneal and pleural mast cell in vitro. We found that spleen cells and thymocytes of normal rats stimulated with PHA in 24 h cultures generated a factor which released histamine and 5-hydroxytryptamine from mast cells, and this ability was potentiated following N. brasiliensis infection of rats - lymphoid cells donors. Pleural mast cells were more sensitive to the action of HRF than peritoneal cells. Rat HRF had an apparent m.w. of 50,000 to 70,000 daltons as determined by gel chromatography and was a heat stable protein inducing histamine release from homologous mast cells in a very rapid (complete in 1-2 min at 37 degrees C), dose and temperature dependent secretory process."} {"id": "PMID:1280500", "title": "PreS antigen expression and anti-preS response in hepatitis B virus infections: relationship to serum HBV-DNA, intrahepatic HBcAg, liver damage and specific T-cell response.", "content": "The diagnostic value of preS antigens and anti-preS antibodies during Hepatitis B virus (HBV) infections have not yet been clearly elucidated. Therefore, the objectives of this study were: 1) to better understand the clinical significance of the expression of both preS1 and preS2 antigens (preS1Ag and preS2Ag) in the serum of chronic HBsAg carriers, and 2) to define the respective role of antibody responses to HBs-, preS2- and preS1-specific determinants in the course of acute hepatitis B (AH-B) infections with different outcomes. Our data showed that the serum preS1Ag/HBsAg ratio correlated well with the level of viral replication (serum HBV-DNA as monitored by PCR assay and liver HBcAg), especially in anti-HBe positive chronic carriers. The complete eradication of virions required a persistent antibody response to conformation-dependent HBs-epitopes, temporally associated with a vigorous T cell response to nucleocapsid antigens. Recovery from hepatitis B can be achieved when there is no early antibody response to preS2- and preS1-proteins, which was found to be transient, concomitant with a flare-up of the liver disease, and preceding anti-HBs production. Information on the patterns of preS antigens and their antibodies remained clouded because of the varying specificities and sensitivities of research methods used in studies to date. We have, therefore, developed original Polyclonal-Monoclonal RadioImmunoAssays (PAb-MAb RIAs) by using monoclonal antibodies (MAbs) having previously well-defined specificities. We could thus detect and quantify simultaneously the three distinct antigenicities of the HBV envelope, HBsAg, preS2Ag and preS1Ag, with the same sensitivity. In this way, the preS1Ag/HBsAg and preS2Ag/HBsAg ratios can be calculated to estimate the serum expression of both preS1Ag and preS2Ag in relation to total HBsAg activity during different stages of chronic HBV infection. For optimal management of the state of HBV replication in chronic viral infection, the detection of HBV-DNA in serum was monitored by the Polymerase Chain Reaction (PCR) assay. We extended our work by investigating the clinical significance of antibody response to preS-specific determinants in patients with AH-B showing different outcomes in both natural course or response to alpha-interferon therapy. In a first attempt, we chose to use the Western Immuno-Blotting Assay (WIBA) to obtain a qualitative assessment of the nature of preS antibody responses. Finally, the cell-mediated immune response to HBV antigens was also studied in several patients with self-limited AH-B leading to a relevant finding which may help to clarify the mechanisms responsible for complete clearance of HBV.", "contents": "PreS antigen expression and anti-preS response in hepatitis B virus infections: relationship to serum HBV-DNA, intrahepatic HBcAg, liver damage and specific T-cell response. The diagnostic value of preS antigens and anti-preS antibodies during Hepatitis B virus (HBV) infections have not yet been clearly elucidated. Therefore, the objectives of this study were: 1) to better understand the clinical significance of the expression of both preS1 and preS2 antigens (preS1Ag and preS2Ag) in the serum of chronic HBsAg carriers, and 2) to define the respective role of antibody responses to HBs-, preS2- and preS1-specific determinants in the course of acute hepatitis B (AH-B) infections with different outcomes. Our data showed that the serum preS1Ag/HBsAg ratio correlated well with the level of viral replication (serum HBV-DNA as monitored by PCR assay and liver HBcAg), especially in anti-HBe positive chronic carriers. The complete eradication of virions required a persistent antibody response to conformation-dependent HBs-epitopes, temporally associated with a vigorous T cell response to nucleocapsid antigens. Recovery from hepatitis B can be achieved when there is no early antibody response to preS2- and preS1-proteins, which was found to be transient, concomitant with a flare-up of the liver disease, and preceding anti-HBs production. Information on the patterns of preS antigens and their antibodies remained clouded because of the varying specificities and sensitivities of research methods used in studies to date. We have, therefore, developed original Polyclonal-Monoclonal RadioImmunoAssays (PAb-MAb RIAs) by using monoclonal antibodies (MAbs) having previously well-defined specificities. We could thus detect and quantify simultaneously the three distinct antigenicities of the HBV envelope, HBsAg, preS2Ag and preS1Ag, with the same sensitivity. In this way, the preS1Ag/HBsAg and preS2Ag/HBsAg ratios can be calculated to estimate the serum expression of both preS1Ag and preS2Ag in relation to total HBsAg activity during different stages of chronic HBV infection. For optimal management of the state of HBV replication in chronic viral infection, the detection of HBV-DNA in serum was monitored by the Polymerase Chain Reaction (PCR) assay. We extended our work by investigating the clinical significance of antibody response to preS-specific determinants in patients with AH-B showing different outcomes in both natural course or response to alpha-interferon therapy. In a first attempt, we chose to use the Western Immuno-Blotting Assay (WIBA) to obtain a qualitative assessment of the nature of preS antibody responses. Finally, the cell-mediated immune response to HBV antigens was also studied in several patients with self-limited AH-B leading to a relevant finding which may help to clarify the mechanisms responsible for complete clearance of HBV."} {"id": "PMID:1280501", "title": "HBc and HBe specificity of monoclonal antibodies against complete and truncated HBc proteins from E. coli.", "content": "We have prepared and used monoclonal antibodies against various populations of full-length and truncated hepatitis B core proteins in order to distinguish between epitopes of HBcAg and HBeAg. Our results show that various epitopes are specific for the different proteins. Certain epitopes, however, are ubiquitous to HBc/e proteins and these are probably exposed on the surface of HBc particles.", "contents": "HBc and HBe specificity of monoclonal antibodies against complete and truncated HBc proteins from E. coli. We have prepared and used monoclonal antibodies against various populations of full-length and truncated hepatitis B core proteins in order to distinguish between epitopes of HBcAg and HBeAg. Our results show that various epitopes are specific for the different proteins. Certain epitopes, however, are ubiquitous to HBc/e proteins and these are probably exposed on the surface of HBc particles."} {"id": "PMID:1280499", "title": "Clinical evaluation of indocyanine green video-angiography in the diagnosis of choroidal neovascular membrane associated with age-related macular degeneration.", "content": "The Authors compared ICG video-angiographic findings in 85 eyes of 78 cases of presumed choroidal neovascular membrane (CNM) associated with age-related macular degeneration with those diagnosed by fluorescein angiography. The detection rate of CNM was 68% with indocyanine green (ICG) video-angiography and 59% with fluorescein angiography. ICG video-angiography can be especially useful for identifying hemorrhagic or exudative detachments of the retinal pigment epithelium. In these cases, detection of CNM by ICG video-angiography was generally far superior to that by fluorescein angiography. However, some CNM in which leakage was identified with fluorescein angiography could not be visualized by ICG video-angiography.", "contents": "Clinical evaluation of indocyanine green video-angiography in the diagnosis of choroidal neovascular membrane associated with age-related macular degeneration. The Authors compared ICG video-angiographic findings in 85 eyes of 78 cases of presumed choroidal neovascular membrane (CNM) associated with age-related macular degeneration with those diagnosed by fluorescein angiography. The detection rate of CNM was 68% with indocyanine green (ICG) video-angiography and 59% with fluorescein angiography. ICG video-angiography can be especially useful for identifying hemorrhagic or exudative detachments of the retinal pigment epithelium. In these cases, detection of CNM by ICG video-angiography was generally far superior to that by fluorescein angiography. However, some CNM in which leakage was identified with fluorescein angiography could not be visualized by ICG video-angiography."} {"id": "PMID:1280502", "title": "Properties of a recombinant yeast-derived hepatitis B surface antigen containing S, preS2 and preS1 antigenic domains.", "content": "Yeast cells have been engineered to express mixed HBsAg particles containing the S and a modified large (L*) protein. Their construction resulted in reduced protease sensitivity, reduced glycosylation and complete inactivation of the polymerized human albumin binding site. The particles exposed the S, preS1 and preS2 antigenic determinants and induced an immune response against the three domains. Highly purified preparations have been obtained and are presently being tested in human volunteers.", "contents": "Properties of a recombinant yeast-derived hepatitis B surface antigen containing S, preS2 and preS1 antigenic domains. Yeast cells have been engineered to express mixed HBsAg particles containing the S and a modified large (L*) protein. Their construction resulted in reduced protease sensitivity, reduced glycosylation and complete inactivation of the polymerized human albumin binding site. The particles exposed the S, preS1 and preS2 antigenic determinants and induced an immune response against the three domains. Highly purified preparations have been obtained and are presently being tested in human volunteers."} {"id": "PMID:1280503", "title": "Antigenicity of synthetic peptides derived from C100 protein of hepatitis C virus.", "content": "Synthetic octapeptides spanning the 119-147 region of the Hepatitis C Virus (HCV) C100 protein were tested on HCV positive sera. The 138-145 region proved to be antigenic and possibly able to avoid undesired cross-reactions.", "contents": "Antigenicity of synthetic peptides derived from C100 protein of hepatitis C virus. Synthetic octapeptides spanning the 119-147 region of the Hepatitis C Virus (HCV) C100 protein were tested on HCV positive sera. The 138-145 region proved to be antigenic and possibly able to avoid undesired cross-reactions."} {"id": "PMID:1280504", "title": "Localization of hepatitis C virus antigen(s) by immunohistochemistry on fixed-embedded liver tissue.", "content": "Using two sources of primary antibodies, we immunohistochemically stained hepatitis C virus-related antigen(s) on fixed-embedded liver specimens. These antigens were localized in the cytoplasm of hepatocytes. The results obtained serologically correlated well with immunohistochemistry.", "contents": "Localization of hepatitis C virus antigen(s) by immunohistochemistry on fixed-embedded liver tissue. Using two sources of primary antibodies, we immunohistochemically stained hepatitis C virus-related antigen(s) on fixed-embedded liver specimens. These antigens were localized in the cytoplasm of hepatocytes. The results obtained serologically correlated well with immunohistochemistry."} {"id": "PMID:1280505", "title": "Identification of HCV-associated antigen(s) in hepatocytes.", "content": "HCV-associated antigens (HCAg) were localized morphologically using immunofluorescence methods. Fluorescence was found in the cytoplasm of individual liver cells or in groups of cells. Nuclear fluorescence was not observed. Blocking and absorption studies suggest that HCAg is related to nucleocapsid or envelope proteins.", "contents": "Identification of HCV-associated antigen(s) in hepatocytes. HCV-associated antigens (HCAg) were localized morphologically using immunofluorescence methods. Fluorescence was found in the cytoplasm of individual liver cells or in groups of cells. Nuclear fluorescence was not observed. Blocking and absorption studies suggest that HCAg is related to nucleocapsid or envelope proteins."} {"id": "PMID:1280506", "title": "Fine specificity of the human T cell response to hepatitis B virus core antigen.", "content": "The fine specificity of the human T cell response to the hepatitis B virus core antigen (HBcAg) was investigated in 23 patients with acute hepatitis B virus (HBV) infection using a panel of short synthetic peptides covering the entire core region. An immunodominant T cell epitope which was recognized by all except one patient, was identified within the core sequence 50-69. Two further important T cell recognition sites were represented by the amino acid sequences 1-20 and 117-131, which were stimulatory for the T cells of 69% and 73% of the patients, respectively. T cell recognition of the synthetic peptides was HLA class II restricted because the peptide-induced T cell proliferation was inhibited by anti-HLA class II but not by anti-HLA class I monoclonal antibodies. These findings may be relevant to the development of future preventive and therapeutic strategies against HBV infection.", "contents": "Fine specificity of the human T cell response to hepatitis B virus core antigen. The fine specificity of the human T cell response to the hepatitis B virus core antigen (HBcAg) was investigated in 23 patients with acute hepatitis B virus (HBV) infection using a panel of short synthetic peptides covering the entire core region. An immunodominant T cell epitope which was recognized by all except one patient, was identified within the core sequence 50-69. Two further important T cell recognition sites were represented by the amino acid sequences 1-20 and 117-131, which were stimulatory for the T cells of 69% and 73% of the patients, respectively. T cell recognition of the synthetic peptides was HLA class II restricted because the peptide-induced T cell proliferation was inhibited by anti-HLA class II but not by anti-HLA class I monoclonal antibodies. These findings may be relevant to the development of future preventive and therapeutic strategies against HBV infection."} {"id": "PMID:1280507", "title": "HCV and blood transfusion.", "content": "Posttransfusion hepatitis remains a threat to transfusion therapy. Testing for increased ALT levels has been used in an attempt to reduce this risk. Presence of the infectious agent, hepatitis C virus (HCV), appears to be a much more sensitive criterion. Stored serum samples from transfusion blood as well as recipients of transfusion were tested by ELISA, RIBA and PCR for the presence of HCV. The results show that RIBA and PCR are about equally sensitive and are able to detect HCV positivity in many sera that might have been otherwise transfused. Routine screening for the presence of virus will dramatically reduce the danger of hepatitis infection to transfusion patients.", "contents": "HCV and blood transfusion. Posttransfusion hepatitis remains a threat to transfusion therapy. Testing for increased ALT levels has been used in an attempt to reduce this risk. Presence of the infectious agent, hepatitis C virus (HCV), appears to be a much more sensitive criterion. Stored serum samples from transfusion blood as well as recipients of transfusion were tested by ELISA, RIBA and PCR for the presence of HCV. The results show that RIBA and PCR are about equally sensitive and are able to detect HCV positivity in many sera that might have been otherwise transfused. Routine screening for the presence of virus will dramatically reduce the danger of hepatitis infection to transfusion patients."} {"id": "PMID:1280508", "title": "Hepatitis in children with thalassemia major.", "content": "Since thalassemia major patients are transfusion dependent, they are at a particularly high risk of contracting post-transfusion hepatitis. In this study, 36 transfusion-dependent children were followed up for evidence of viral hepatitis. Of 23 with increased ALT levels, 17 were anti-CMV and 12 were anti-HCV positive, 9 were positive for both CMV and HCV. Of 13 children with normal transaminase levels, 5 were CMV positive and 3 were HCV positive. These results show that CMV may be a very common cause of non-A, non-B hepatitis in transfusion dependent thalassemic children.", "contents": "Hepatitis in children with thalassemia major. Since thalassemia major patients are transfusion dependent, they are at a particularly high risk of contracting post-transfusion hepatitis. In this study, 36 transfusion-dependent children were followed up for evidence of viral hepatitis. Of 23 with increased ALT levels, 17 were anti-CMV and 12 were anti-HCV positive, 9 were positive for both CMV and HCV. Of 13 children with normal transaminase levels, 5 were CMV positive and 3 were HCV positive. These results show that CMV may be a very common cause of non-A, non-B hepatitis in transfusion dependent thalassemic children."} {"id": "PMID:1280509", "title": "Prevalence of antibodies to hepatitis C virus in patients with hepatocellular carcinoma in Austria.", "content": "In 12 of 54 (22%) patients with histologically verified hepatocellular carcinoma, antibodies to hepatitis C virus were found. In patients with hepatocellular carcinoma the frequency of anti-hepatitis C virus positivity was similar whether cirrhosis (6 of 22 patients (27%)) was present or not (2 of 15 (13%)). Out of 54, 23 patients (43%) were negative both for hepatitis B or C markers. Out of 53, 22 (42%) had positive hepatitis B markers, 8 of 22 were HBsAg positive. Patients with hepatocellular carcinoma and cirrhosis had a higher percentage of hepatitis B virus markers than patients with cirrhosis without hepatocellular carcinoma. Our of 70 patients with cirrhosis but without hepatocellular carcinoma, 24 (34%) had antibodies to hepatitis C virus. Our data of similar frequencies of antibodies to hepatitis C virus in patients with hepatocellular carcinoma or with liver cirrhosis but without hepatocellular carcinoma indicate that at least in Austrian patients, hepatitis C virus infections are not an important factor for development of hepatocellular carcinoma.", "contents": "Prevalence of antibodies to hepatitis C virus in patients with hepatocellular carcinoma in Austria. In 12 of 54 (22%) patients with histologically verified hepatocellular carcinoma, antibodies to hepatitis C virus were found. In patients with hepatocellular carcinoma the frequency of anti-hepatitis C virus positivity was similar whether cirrhosis (6 of 22 patients (27%)) was present or not (2 of 15 (13%)). Out of 54, 23 patients (43%) were negative both for hepatitis B or C markers. Out of 53, 22 (42%) had positive hepatitis B markers, 8 of 22 were HBsAg positive. Patients with hepatocellular carcinoma and cirrhosis had a higher percentage of hepatitis B virus markers than patients with cirrhosis without hepatocellular carcinoma. Our of 70 patients with cirrhosis but without hepatocellular carcinoma, 24 (34%) had antibodies to hepatitis C virus. Our data of similar frequencies of antibodies to hepatitis C virus in patients with hepatocellular carcinoma or with liver cirrhosis but without hepatocellular carcinoma indicate that at least in Austrian patients, hepatitis C virus infections are not an important factor for development of hepatocellular carcinoma."} {"id": "PMID:1280510", "title": "Serotype A and B strains of bean common mosaic virus are two distinct potyviruses.", "content": "The serological relationships among strains of bean common mosaic virus (BCMV) (genus Potyvirus, family Potyviridae) were investigated by testing 13 isolates of the 10 known BCMV pathotypes with two monoclonal antibodies and six antisera to BCMV strains. In addition, other properties of serologically distinct BCMV strains were compared. Two groups of BCMV strains were obtained by ELISA and Western blot serology: serotype A contained the BCMV strains NL3, NL5, and NL8 and serotype B contained the BCMV strains NL1, NL2, NL4, NL6, US4, NL7, NY15, and Fla. SDS polyacrylamide gel electrophoresis and Western blotting of freshly purified preparations, and of extracts from leaves infected with eleven BCMV strains showed that the apparent molecular mass of the capsid protein of the serotype A isolates NL3, NL5, and NL8 are lower (about M(r) 33,000) than those of the serotype B isolates (M(r) 34,500 to 35,000). The normal lengths of the particles of the serotype A isolates were shorter (810-818 nm) than those of most isolates (except NL6 and NY15) of serotype B (847-886 nm). All isolates studied induced cytoplasmic pinwheel and scroll inclusions. Cells infected with serotype A isolates contained a specific type of proliferated endoplasmic reticulum which was never found in cells infected with serotype B isolates. The capsid protein gene of a representative member of each serotype was cloned and sequenced. Molecular mass calculations based upon nucleotide sequence-derived amino acid sequences yielded M(r) of 29,662 and 32,489 for the capsid proteins of the serotype A isolate NL8 and the serotype B isolate NL4, respectively. Comparison of the coat-protein sequences showed considerable differences at the N-termini whereas the core regions and the C-termini appeared to be highly conserved. Marked differences were also observed within the 3' non-coding regions of cloned cDNAs of NL 4 and NL 8. The striking differences between the two serotypes of BCMV strongly suggest that they be classified as two distinct potyviruses which naturally infect Phaseolus beans.", "contents": "Serotype A and B strains of bean common mosaic virus are two distinct potyviruses. The serological relationships among strains of bean common mosaic virus (BCMV) (genus Potyvirus, family Potyviridae) were investigated by testing 13 isolates of the 10 known BCMV pathotypes with two monoclonal antibodies and six antisera to BCMV strains. In addition, other properties of serologically distinct BCMV strains were compared. Two groups of BCMV strains were obtained by ELISA and Western blot serology: serotype A contained the BCMV strains NL3, NL5, and NL8 and serotype B contained the BCMV strains NL1, NL2, NL4, NL6, US4, NL7, NY15, and Fla. SDS polyacrylamide gel electrophoresis and Western blotting of freshly purified preparations, and of extracts from leaves infected with eleven BCMV strains showed that the apparent molecular mass of the capsid protein of the serotype A isolates NL3, NL5, and NL8 are lower (about M(r) 33,000) than those of the serotype B isolates (M(r) 34,500 to 35,000). The normal lengths of the particles of the serotype A isolates were shorter (810-818 nm) than those of most isolates (except NL6 and NY15) of serotype B (847-886 nm). All isolates studied induced cytoplasmic pinwheel and scroll inclusions. Cells infected with serotype A isolates contained a specific type of proliferated endoplasmic reticulum which was never found in cells infected with serotype B isolates. The capsid protein gene of a representative member of each serotype was cloned and sequenced. Molecular mass calculations based upon nucleotide sequence-derived amino acid sequences yielded M(r) of 29,662 and 32,489 for the capsid proteins of the serotype A isolate NL8 and the serotype B isolate NL4, respectively. Comparison of the coat-protein sequences showed considerable differences at the N-termini whereas the core regions and the C-termini appeared to be highly conserved. Marked differences were also observed within the 3' non-coding regions of cloned cDNAs of NL 4 and NL 8. The striking differences between the two serotypes of BCMV strongly suggest that they be classified as two distinct potyviruses which naturally infect Phaseolus beans."} {"id": "PMID:1280511", "title": "Potyviruses, monoclonal antibodies, and antigenic sites.", "content": "Virus-specific and cross-reactive monoclonal antibodies have been produced to at least 19 different aphid-transmitted potyviruses. This report summarizes the development of these monoclonal antibodies as well as presents information on the delineation of the virus-specific and group-common epitopes defined by these monoclonal antibodies. Virus-specific and group-common antigenic determinants were mapped by a variety of techniques, including analysis of antigen: antibody reactivity patterns, determination of N-terminal vs. trypsin-resistant core peptide-specificity, immunoanalysis of overlapping synthetic peptides, and immunoanalysis of bacterially expressed coat-protein gene products. Of those monoclonal antibodies that have been examined, monoclonal antibody-defined virus-specific epitopes are virion surface-located within the 30+ amino acid amino terminus, whereas the group-common epitopes are found in the trypsin-resistant core protein not usually located on the virion surface, as has been shown previously with certain polyclonal antibodies. New information is presented on the analysis of bean yellow mosaic virus amino terminal epitopes as well as on the identification of amino terminal antigenic determinants shared between strains of bean yellow mosaic virus and pepper mottle virus. A recommendation on the evaluation and use of a panel of potyvirus broad-spectrum reacting monoclonals as reference monoclonal antibodies for the detection and classification of aphid-transmitted potyviruses is also presented.", "contents": "Potyviruses, monoclonal antibodies, and antigenic sites. Virus-specific and cross-reactive monoclonal antibodies have been produced to at least 19 different aphid-transmitted potyviruses. This report summarizes the development of these monoclonal antibodies as well as presents information on the delineation of the virus-specific and group-common epitopes defined by these monoclonal antibodies. Virus-specific and group-common antigenic determinants were mapped by a variety of techniques, including analysis of antigen: antibody reactivity patterns, determination of N-terminal vs. trypsin-resistant core peptide-specificity, immunoanalysis of overlapping synthetic peptides, and immunoanalysis of bacterially expressed coat-protein gene products. Of those monoclonal antibodies that have been examined, monoclonal antibody-defined virus-specific epitopes are virion surface-located within the 30+ amino acid amino terminus, whereas the group-common epitopes are found in the trypsin-resistant core protein not usually located on the virion surface, as has been shown previously with certain polyclonal antibodies. New information is presented on the analysis of bean yellow mosaic virus amino terminal epitopes as well as on the identification of amino terminal antigenic determinants shared between strains of bean yellow mosaic virus and pepper mottle virus. A recommendation on the evaluation and use of a panel of potyvirus broad-spectrum reacting monoclonals as reference monoclonal antibodies for the detection and classification of aphid-transmitted potyviruses is also presented."} {"id": "PMID:1280512", "title": "The immune response to and expression of cross-reactive retroviral gag sequences in autoimmune disease.", "content": "To examine the immune response to retroviral gag sequences in autoimmune disease, we measured antibody levels to synthetic peptides representing the major epitopes on HTLV-1 p19 gag and a homologous sequence on the endogenous retrovirus, HRES-1, in sera from 121 patients with autoimmune disease and 52 healthy controls. In the absence of HTLV-1 antibodies, using a conventional diagnostic assay, significantly elevated levels of antibodies to the HTLV-1 peptide were found in 23% of multiple sclerosis and 20% of anti-Sm antibody positive systemic lupus erythematosus patients. Elevated antibody levels to HRES-1 were found in 32% of Sj\u00f6gren's syndrome and 19% of multiple sclerosis patients. Evidence of reactivity with both HTLV-1 and HRES-1 was found in human sera and cross-reactivity demonstrated with affinity purified rabbit anti-peptide antibodies. Expression of HRES-1, detected by antibodies and Northern blots, was found in lymphoblastoid cells, salivary gland biopsy sections and salivary gland epithelial cells in culture. This study confirms previous reports of low levels of anti-retroviral gag antibodies in autoimmune disease. The cross-reactions support the concept that reports of elevated HTLV-1 antibodies may be due to an endogenous agent such as HRES-1. The expression of HRES-1 salivary gland may explain its antigenicity in a small proportion of Sj\u00f6gren's syndrome patients as well as suggesting mechanisms whereby it may contribute to the chronic inflammation of autoimmune disease.", "contents": "The immune response to and expression of cross-reactive retroviral gag sequences in autoimmune disease. To examine the immune response to retroviral gag sequences in autoimmune disease, we measured antibody levels to synthetic peptides representing the major epitopes on HTLV-1 p19 gag and a homologous sequence on the endogenous retrovirus, HRES-1, in sera from 121 patients with autoimmune disease and 52 healthy controls. In the absence of HTLV-1 antibodies, using a conventional diagnostic assay, significantly elevated levels of antibodies to the HTLV-1 peptide were found in 23% of multiple sclerosis and 20% of anti-Sm antibody positive systemic lupus erythematosus patients. Elevated antibody levels to HRES-1 were found in 32% of Sj\u00f6gren's syndrome and 19% of multiple sclerosis patients. Evidence of reactivity with both HTLV-1 and HRES-1 was found in human sera and cross-reactivity demonstrated with affinity purified rabbit anti-peptide antibodies. Expression of HRES-1, detected by antibodies and Northern blots, was found in lymphoblastoid cells, salivary gland biopsy sections and salivary gland epithelial cells in culture. This study confirms previous reports of low levels of anti-retroviral gag antibodies in autoimmune disease. The cross-reactions support the concept that reports of elevated HTLV-1 antibodies may be due to an endogenous agent such as HRES-1. The expression of HRES-1 salivary gland may explain its antigenicity in a small proportion of Sj\u00f6gren's syndrome patients as well as suggesting mechanisms whereby it may contribute to the chronic inflammation of autoimmune disease."} {"id": "PMID:1280513", "title": "Effect of substance P on detrusor muscle in rats with diabetic cystopathy.", "content": "Diabetic cystopathy (DCP) is a well known complication in diabetes mellitus (DM). In the present experimental study, DM was induced in rats by streptozotocin and DCP was confirmed on cystometry. In vitro studies on detrusor strips from diabetic rats showed an increased contractile response to substance P (SP) compared with controls, indicating denervation supersensitivity. A decreased response to capsaicin in diabetic detrusor strips indicated a decreased neuronal content of SP or a diminished number of SP-containing sensory nerves. This suggests that DM induces alterations in nerves containing SP which may be at least partly responsible for sensory loss and the development of DCP.", "contents": "Effect of substance P on detrusor muscle in rats with diabetic cystopathy. Diabetic cystopathy (DCP) is a well known complication in diabetes mellitus (DM). In the present experimental study, DM was induced in rats by streptozotocin and DCP was confirmed on cystometry. In vitro studies on detrusor strips from diabetic rats showed an increased contractile response to substance P (SP) compared with controls, indicating denervation supersensitivity. A decreased response to capsaicin in diabetic detrusor strips indicated a decreased neuronal content of SP or a diminished number of SP-containing sensory nerves. This suggests that DM induces alterations in nerves containing SP which may be at least partly responsible for sensory loss and the development of DCP."} {"id": "PMID:1280514", "title": "Cholinergic, monoaminergic and peptidergic innervation of the primary visual centers in the brain of the lizards Gekko gecko and Gallotia galloti.", "content": "In order to study the relationship between retinal projections and immunohistochemically identified neurotransmitter systems in the primary visual centers of the brain in lizards, intraocular injections of horseradish peroxidase were combined with immunohistochemistry. Antibodies raised against six substances were applied: choline acetyltransferase (ChAT), serotonin (5-HT), tyrosine hydroxylase (TH), dopamine (DA), substance P (SP), and leu-enkephalin (LENK). In the primary visual centers of the lizards Gekko gecko and Gallotia galloti, notable overlap was observed between retinofugal fibers with: 1) ChAT-immunoreactive fibers in almost all primary visual centers; 2) 5-HT-immunoreactive fibers in the ventral lateral geniculate body and the basal optic nucleus; 3) TH-immunoreactive fibers in the nucleus ovalis and the dorsal lateral geniculate body; 4) SP- and LENK-immunoreactive fibers in the perirotundal belt; and 5) TH- and SP-immunoreactive fibers in the pretectal posterodorsal nucleus. The latter nucleus also contains dopaminergic cell bodies that lie outside the retinal target area but have dendrites extending into it. Several differences were noted in the distribution of 5-HT, TH-, DA-, and LENK-immunoreactive fibers in the tectum of the midbrain in the two species studied. Distinct laminae of 5-HT-immunoreactive fibers (layer 9) and TH- and DA-immunoreactive fibers (layers 9 and 11) are present in G. gecko but absent or, at least, less distinct in G. galloti. On the contrary, the optic layers in the tectum of G. galloti show a rather dense plexus of LENK immunoreactive fibers, whereas the corresponding layers in G. gecko are devoid of LENK-immunoreactivity. Since only a very few ChAT immunoreactive fibers were observed in the optic nerve of G. galloti, most of the observed immunoreactive fibers in the primary visual centers are considered to have an extraretinal origin. Putative sources of the cholinergic, the monoaminergic, and the peptidergic innervation of the primary visual centers in reptiles include the isthmic nucleus, the raphe nuclei, the substantia nigra and the nucleus of the posterior commissure, as reported in other amniotes.", "contents": "Cholinergic, monoaminergic and peptidergic innervation of the primary visual centers in the brain of the lizards Gekko gecko and Gallotia galloti. In order to study the relationship between retinal projections and immunohistochemically identified neurotransmitter systems in the primary visual centers of the brain in lizards, intraocular injections of horseradish peroxidase were combined with immunohistochemistry. Antibodies raised against six substances were applied: choline acetyltransferase (ChAT), serotonin (5-HT), tyrosine hydroxylase (TH), dopamine (DA), substance P (SP), and leu-enkephalin (LENK). In the primary visual centers of the lizards Gekko gecko and Gallotia galloti, notable overlap was observed between retinofugal fibers with: 1) ChAT-immunoreactive fibers in almost all primary visual centers; 2) 5-HT-immunoreactive fibers in the ventral lateral geniculate body and the basal optic nucleus; 3) TH-immunoreactive fibers in the nucleus ovalis and the dorsal lateral geniculate body; 4) SP- and LENK-immunoreactive fibers in the perirotundal belt; and 5) TH- and SP-immunoreactive fibers in the pretectal posterodorsal nucleus. The latter nucleus also contains dopaminergic cell bodies that lie outside the retinal target area but have dendrites extending into it. Several differences were noted in the distribution of 5-HT, TH-, DA-, and LENK-immunoreactive fibers in the tectum of the midbrain in the two species studied. Distinct laminae of 5-HT-immunoreactive fibers (layer 9) and TH- and DA-immunoreactive fibers (layers 9 and 11) are present in G. gecko but absent or, at least, less distinct in G. galloti. On the contrary, the optic layers in the tectum of G. galloti show a rather dense plexus of LENK immunoreactive fibers, whereas the corresponding layers in G. gecko are devoid of LENK-immunoreactivity. Since only a very few ChAT immunoreactive fibers were observed in the optic nerve of G. galloti, most of the observed immunoreactive fibers in the primary visual centers are considered to have an extraretinal origin. Putative sources of the cholinergic, the monoaminergic, and the peptidergic innervation of the primary visual centers in reptiles include the isthmic nucleus, the raphe nuclei, the substantia nigra and the nucleus of the posterior commissure, as reported in other amniotes."} {"id": "PMID:1280515", "title": "The formation of a 'pseudo-nerve' in silicone chambers in the absence of regenerating axons.", "content": "The formation of a regenerate between sciatic nerve segments or stumps inserted into Y-tunnelled silicone chambers was studied under conditions where regenerating axons were prevented from entering the chamber. This was accomplished by using an isolated segment of the nerve as a proximal insert. After one week, a cellular regenerate spanned the proximal and distal inserts. The size of the regenerate increased if circulation was preserved in the distal inserts. At four weeks, a perineurium-like sheath surrounded the regenerate and longitudinally oriented Schwann cell columns could be observed throughout the regenerate. A similar 'pseudo-nerve' formed towards a piece of distally inserted tendon. Thus, the information required for the formation of a nerve-like structure is inherent to the non-neuronal cells entering the chamber. Schwann cells, in contrast to regenerating axons, do not exhibit preferential growth towards nervous tissue.", "contents": "The formation of a 'pseudo-nerve' in silicone chambers in the absence of regenerating axons. The formation of a regenerate between sciatic nerve segments or stumps inserted into Y-tunnelled silicone chambers was studied under conditions where regenerating axons were prevented from entering the chamber. This was accomplished by using an isolated segment of the nerve as a proximal insert. After one week, a cellular regenerate spanned the proximal and distal inserts. The size of the regenerate increased if circulation was preserved in the distal inserts. At four weeks, a perineurium-like sheath surrounded the regenerate and longitudinally oriented Schwann cell columns could be observed throughout the regenerate. A similar 'pseudo-nerve' formed towards a piece of distally inserted tendon. Thus, the information required for the formation of a nerve-like structure is inherent to the non-neuronal cells entering the chamber. Schwann cells, in contrast to regenerating axons, do not exhibit preferential growth towards nervous tissue."} {"id": "PMID:1280516", "title": "The C-terminal fragment of substance P enhances dopamine release in nucleus accumbens but not in neostriatum in freely moving rats.", "content": "The in vivo microdialysis technique was used to study the effects of carboxyl or amino terminal sequences of substance P on the extracellular concentrations of dopamine, its metabolites dihydroxyphenylacetic acid and homovanillic acid, as well as on 5-hydroxyindoleacetic acid, in neostriatum and nucleus accumbens of freely moving rats. The i.p. administration of 37 nmol/kg of the substance P C-terminal heptapeptide analog [pGlu5, MePhe8, Sar9]SP5-11 (DiMe-C7) caused an increase in extracellular dopamine concentrations in nucleus accumbens but not in neostriatum. The administration of the equimolar dose of the heptapeptide N-terminal fragment substance P 1-7 (SP1-7) did not have an effect in either structure. No changes were observed in the extracellular concentrations of the metabolites after the administration of either substance. These results are discussed with respect to the reinforcing effects of substance P and its C-terminal sequence, which may be mediated via dopamine release in the nucleus accumbens.", "contents": "The C-terminal fragment of substance P enhances dopamine release in nucleus accumbens but not in neostriatum in freely moving rats. The in vivo microdialysis technique was used to study the effects of carboxyl or amino terminal sequences of substance P on the extracellular concentrations of dopamine, its metabolites dihydroxyphenylacetic acid and homovanillic acid, as well as on 5-hydroxyindoleacetic acid, in neostriatum and nucleus accumbens of freely moving rats. The i.p. administration of 37 nmol/kg of the substance P C-terminal heptapeptide analog [pGlu5, MePhe8, Sar9]SP5-11 (DiMe-C7) caused an increase in extracellular dopamine concentrations in nucleus accumbens but not in neostriatum. The administration of the equimolar dose of the heptapeptide N-terminal fragment substance P 1-7 (SP1-7) did not have an effect in either structure. No changes were observed in the extracellular concentrations of the metabolites after the administration of either substance. These results are discussed with respect to the reinforcing effects of substance P and its C-terminal sequence, which may be mediated via dopamine release in the nucleus accumbens."} {"id": "PMID:1280517", "title": "Serial reconstruction of beta-protein amyloid plaques: relationship to microvessels and size distribution.", "content": "The suggestion that the amyloid plaques in Alzheimer disease are formed by abnormal leakage from microvessels is mainly based on the finding that many plaques are topographically associated with microvessels. However, because the microvessel network is dense and amyloid plaques are numerous, the frequently observed association may result from chance contact, especially for larger plaques. Therefore, we determined the frequency of this association as a variable of plaque size. If all the amyloid plaques are associated with microvessels, a constant and high rate of association would be expected for all plaque sizes. On the other hand, if the association is a chance contact, larger plaques would show more frequent contact than smaller ones. Sections were double-immunostained for amyloid plaques and microvessels with antibodies raised against beta-protein and collagen type IV, respectively. Amyloid plaques were reconstructed using 12 serial sections (7 microns thick) from the entorhinal cortex of two Alzheimer patients. With reconstruction we determined the size distribution of amyloid plaques as well as the influence of size on vascular association. All the amyloid plaques larger than 42 microns were associated with microvessels, however, the smaller the amyloid plaques, the less frequently they were associated with microvessels. Interestingly, although diffuse amyloid plaques occur in all size classes, core-containing amyloid plaques have a more discrete size. We conclude that the topographical relationship between amyloid deposition and capillaries does not support the leakage theory for amyloid plaque formation.", "contents": "Serial reconstruction of beta-protein amyloid plaques: relationship to microvessels and size distribution. The suggestion that the amyloid plaques in Alzheimer disease are formed by abnormal leakage from microvessels is mainly based on the finding that many plaques are topographically associated with microvessels. However, because the microvessel network is dense and amyloid plaques are numerous, the frequently observed association may result from chance contact, especially for larger plaques. Therefore, we determined the frequency of this association as a variable of plaque size. If all the amyloid plaques are associated with microvessels, a constant and high rate of association would be expected for all plaque sizes. On the other hand, if the association is a chance contact, larger plaques would show more frequent contact than smaller ones. Sections were double-immunostained for amyloid plaques and microvessels with antibodies raised against beta-protein and collagen type IV, respectively. Amyloid plaques were reconstructed using 12 serial sections (7 microns thick) from the entorhinal cortex of two Alzheimer patients. With reconstruction we determined the size distribution of amyloid plaques as well as the influence of size on vascular association. All the amyloid plaques larger than 42 microns were associated with microvessels, however, the smaller the amyloid plaques, the less frequently they were associated with microvessels. Interestingly, although diffuse amyloid plaques occur in all size classes, core-containing amyloid plaques have a more discrete size. We conclude that the topographical relationship between amyloid deposition and capillaries does not support the leakage theory for amyloid plaque formation."} {"id": "PMID:1280518", "title": "Three types of sodium channels in adult rat dorsal root ganglion neurons.", "content": "Several types of Na+ currents have previously been demonstrated in dorsal root ganglion (DRG) neurons isolated from neonatal rats, but their expression in adult neurons has not been studied. Na+ current properties in adult dorsal root ganglion (DRG) neurons of defined size class were investigated in isolated neurons maintained in primary culture using a combination of microelectrode current clamp, patch voltage clamp and immunocytochemical techniques. Intracellular current clamp recordings identified differing relative contributions of TTX-sensitive and -resistant inward currents to action potential waveforms in DRG neuronal populations of defined size. Patch voltage clamp recordings identified three distinct kinetic types of Na+ current differentially distributed among these size classes of DRG neurons. 'Small' DRG neurons co-express two types of Na+ current: (i) a rapidly-inactivating, TTX-sensitive 'fast' current and (ii) a slowly-activating and -inactivating, TTX-resistant 'slow' current. The TTX-sensitive Na+ current in these cells was almost completely inactivated at typical resting potentials. 'Large' cells expressed a single TTX-sensitive Na+ current identified as 'intermediate' by its inactivation rate constants. 'Medium'-sized neurons either co-expressed 'fast' and 'slow' current or expressed only 'intermediate' current. Na+ channel expression in these size classes was also measured by immunocytochemical techniques. An antibody against brain-type Na+ channels (Ab7493)10 labeled small and large neurons with similar intensity. These results demonstrate that three types of Na+ currents can be detected which correlate with electrogenic properties of physiologically and anatomically distinct populations of adult rat DRG neurons.", "contents": "Three types of sodium channels in adult rat dorsal root ganglion neurons. Several types of Na+ currents have previously been demonstrated in dorsal root ganglion (DRG) neurons isolated from neonatal rats, but their expression in adult neurons has not been studied. Na+ current properties in adult dorsal root ganglion (DRG) neurons of defined size class were investigated in isolated neurons maintained in primary culture using a combination of microelectrode current clamp, patch voltage clamp and immunocytochemical techniques. Intracellular current clamp recordings identified differing relative contributions of TTX-sensitive and -resistant inward currents to action potential waveforms in DRG neuronal populations of defined size. Patch voltage clamp recordings identified three distinct kinetic types of Na+ current differentially distributed among these size classes of DRG neurons. 'Small' DRG neurons co-express two types of Na+ current: (i) a rapidly-inactivating, TTX-sensitive 'fast' current and (ii) a slowly-activating and -inactivating, TTX-resistant 'slow' current. The TTX-sensitive Na+ current in these cells was almost completely inactivated at typical resting potentials. 'Large' cells expressed a single TTX-sensitive Na+ current identified as 'intermediate' by its inactivation rate constants. 'Medium'-sized neurons either co-expressed 'fast' and 'slow' current or expressed only 'intermediate' current. Na+ channel expression in these size classes was also measured by immunocytochemical techniques. An antibody against brain-type Na+ channels (Ab7493)10 labeled small and large neurons with similar intensity. These results demonstrate that three types of Na+ currents can be detected which correlate with electrogenic properties of physiologically and anatomically distinct populations of adult rat DRG neurons."} {"id": "PMID:1280519", "title": "Release of neuropeptide FF (FLFQPQRF-NH2) from rat spinal cord.", "content": "Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord.", "contents": "Release of neuropeptide FF (FLFQPQRF-NH2) from rat spinal cord. Neuropeptide FF (FLFQPQRF-NH2), originally isolated from bovine brain, is an FMRF-NH2-like peptide with morphine-modulating activity. Neuropeptide FF (NPFF) is highly localized in the dorsal spinal cords where there are also specific NPFF binding sites. Furthermore, there have been studies indicating that NPFF may participate in the regulation of pain threshold in the spinal cord. However, whether NPFF can be released from the spinal cord is not known. The present experiments, using an in vitro superfusion of an isolated whole rat spinal cord, demonstrated that high concentrations of KCl or substance P caused a release of NPFF immunoreactive material (IR) from the spinal cord into the perfusion medium in a calcium-dependent manner. Substance P (1-11) also produced a detectable release of NPFF-IR in vivo although the response was quite variable. The released NPFF-IR was analyzed by an HPLC study and found to consist of NPFF and other minor immunoreactive peptides. Further studies with substance P-related peptides showed that the in vitro release of NPFF-IR could also be induced by substance P (1-7) but not by [pGlu5,Me-Phe8,Sar9]-substance P (5-11) or substance K. These results suggest that the specific substance P receptor (SP-N), which is recognized by both substance P (1-11) and substance P (1-7) rather than the tachykinin receptor, is involved in NPFF secretion from the spinal cord. In view of the role of substance P (1-11) and substance P (1-7) in sensory transmission, the results of this study further support the role of NPFF in the modulation of antinociception in the spinal cord."} {"id": "PMID:1280520", "title": "Kindling causes changes in the composition of the astrocytic cytoskeleton.", "content": "Changes in the astrocytic cytoskeleton were examined in amygdala kindled rats using immunocytochemical techniques. One week following kindling, there was a dramatic increase in immunoreactivity to glial fibrillary acidic protein and vimentin in astrocytes throughout amygdala, pyriform cortex and hippocampus bilaterally. Since these changes occurred in anatomical sites involved in the propagation of kindled seizures, the observed cytoskeletal reorganization in astrocytes may signify important functional alterations in the kindled brain.", "contents": "Kindling causes changes in the composition of the astrocytic cytoskeleton. Changes in the astrocytic cytoskeleton were examined in amygdala kindled rats using immunocytochemical techniques. One week following kindling, there was a dramatic increase in immunoreactivity to glial fibrillary acidic protein and vimentin in astrocytes throughout amygdala, pyriform cortex and hippocampus bilaterally. Since these changes occurred in anatomical sites involved in the propagation of kindled seizures, the observed cytoskeletal reorganization in astrocytes may signify important functional alterations in the kindled brain."} {"id": "PMID:1280521", "title": "Expression of insulin-like growth factor I by astrocytes in response to injury.", "content": "Astrocytes are known to express several growth factors in response to injury and neurological disease. Insulin-like growth factor I (IGF-I) induces astrocytes to divide in vitro and is expressed by developing, but not adult astrocytes both in vivo and in vitro. We tested whether IGF-I is re-expressed by reactive astrocytes in response to injury. We found that astrocytes surrounding the lesioned parenchyma after introduction of a cannula through the cerebral cortex, hippocampus and midbrain contain high levels of immunoreactive IGF-I, as determined by immunocytochemistry using a highly sensitive and specific anti-IGF-I monoclonal antibody. Interestingly, the contralateral hippocampus also contained IGF-I positive astrocytes although in substantial lower numbers. Intact animals showed no detectable IGF-I immunoreactivity in astrocytes. IGF-I was detected at the first time point tested after the lesion was made, 1 week, and for at least 1 month thereafter. Reactive astrocytes expressing high levels of glial fibrillary acidic protein were found in a much wider distribution all along the lesioned area and beyond. We conclude that mechanical injury of the brain induces a specific pattern of expression of IGF-I by a subpopulation of astrocytes. These findings suggest that IGF-I is participating in the response of astrocytes to injury.", "contents": "Expression of insulin-like growth factor I by astrocytes in response to injury. Astrocytes are known to express several growth factors in response to injury and neurological disease. Insulin-like growth factor I (IGF-I) induces astrocytes to divide in vitro and is expressed by developing, but not adult astrocytes both in vivo and in vitro. We tested whether IGF-I is re-expressed by reactive astrocytes in response to injury. We found that astrocytes surrounding the lesioned parenchyma after introduction of a cannula through the cerebral cortex, hippocampus and midbrain contain high levels of immunoreactive IGF-I, as determined by immunocytochemistry using a highly sensitive and specific anti-IGF-I monoclonal antibody. Interestingly, the contralateral hippocampus also contained IGF-I positive astrocytes although in substantial lower numbers. Intact animals showed no detectable IGF-I immunoreactivity in astrocytes. IGF-I was detected at the first time point tested after the lesion was made, 1 week, and for at least 1 month thereafter. Reactive astrocytes expressing high levels of glial fibrillary acidic protein were found in a much wider distribution all along the lesioned area and beyond. We conclude that mechanical injury of the brain induces a specific pattern of expression of IGF-I by a subpopulation of astrocytes. These findings suggest that IGF-I is participating in the response of astrocytes to injury."} {"id": "PMID:1280522", "title": "Localization of amyloid precursor protein in selective postsynaptic densities of rat cortical neurons.", "content": "One of the hallmarks of Alzheimer pathology is extracellular deposition of beta-amyloid protein (BAP) which is derived from a larger glycoprotein called amyloid precursor protein (APP). Although APP has often been described as a surface membrane protein, such a localization has not previously been demonstrated at the light or electron microscopic level. We now report the results of immunoelectron microscopy using three specific antibodies against different synthetic fragments of APP. All three antibodies demonstrated a major localization to organelles such as the Golgi apparatus, endoplasmic reticulum and vesicular-like structures. A minor proportion of staining with all three was on selective postsynaptic membranes of asymmetrical synapses, whereas staining of presynaptic membranes was not observed. The morphological evidence suggests that one role of APP may be in association with the function of selective synapses.", "contents": "Localization of amyloid precursor protein in selective postsynaptic densities of rat cortical neurons. One of the hallmarks of Alzheimer pathology is extracellular deposition of beta-amyloid protein (BAP) which is derived from a larger glycoprotein called amyloid precursor protein (APP). Although APP has often been described as a surface membrane protein, such a localization has not previously been demonstrated at the light or electron microscopic level. We now report the results of immunoelectron microscopy using three specific antibodies against different synthetic fragments of APP. All three antibodies demonstrated a major localization to organelles such as the Golgi apparatus, endoplasmic reticulum and vesicular-like structures. A minor proportion of staining with all three was on selective postsynaptic membranes of asymmetrical synapses, whereas staining of presynaptic membranes was not observed. The morphological evidence suggests that one role of APP may be in association with the function of selective synapses."} {"id": "PMID:1280523", "title": "Lindane-induced convulsions in NMRI and OF1 mice: antagonism with (+)MK-801 and voltage-dependent calcium channel blockers.", "content": "The convulsant profile of lindane was investigated in OF1 and NMRI mice lines in relation to other convulsants acting at the GABAA and NMDA receptor complexes. Thus, a specific GABA-gated chloride channel blocker, PTX, a GABAA receptor antagonist, PTZ, and an excitatory amino acid receptor agonist, NMDA, were used. Antagonism of the convulsant effects of each of these drugs was investigated with (+)MK-801, a blocker of the NMDA-operated cation channel, and with nifedipine, a voltage-dependent calcium channel antagonist. While no differences in potency for PTX or PTZ to induce seizures were observed between OF1 and NMRI mice, lindane was approximately 80 and 90% more potent in its ability to induce seizures and lethality, respectively, in OF1 than in NMRI mice. Brain lindane concentrations at the moment of convulsion, measured after ED100 doses of lindane (400 and 200 mg/kg for NMRI and OF1 mice, respectively), did not differ between OF1 and NMRI mice, suggesting that the different potency of lindane between these mouse lines is a consequence of pharmacokinetic factors. Furthermore, (+)MK-801 antagonized seizures induced by either lindane, PTX or PTZ with similar potencies in both mouse lines. These results, coupled with the different pharmacokinetics of lindane in OF1 and NMRI mice, suggest that the distinct effects of lindane in these mice are not mediated by different activities at either NMDA or GABAA receptor complexes. Nonetheless, nifedipine antagonized lindane-induced seizures with a three-fold higher potency in NMRI than in OF1 mice. In contrast, nifedipine failed to antagonize PTX and PTZ convulsions in both OF1 and NMRI mice. These results suggest that besides the GABAA receptor complex other mechanisms related to calcium mobilization may be involved in the convulsant action of lindane.", "contents": "Lindane-induced convulsions in NMRI and OF1 mice: antagonism with (+)MK-801 and voltage-dependent calcium channel blockers. The convulsant profile of lindane was investigated in OF1 and NMRI mice lines in relation to other convulsants acting at the GABAA and NMDA receptor complexes. Thus, a specific GABA-gated chloride channel blocker, PTX, a GABAA receptor antagonist, PTZ, and an excitatory amino acid receptor agonist, NMDA, were used. Antagonism of the convulsant effects of each of these drugs was investigated with (+)MK-801, a blocker of the NMDA-operated cation channel, and with nifedipine, a voltage-dependent calcium channel antagonist. While no differences in potency for PTX or PTZ to induce seizures were observed between OF1 and NMRI mice, lindane was approximately 80 and 90% more potent in its ability to induce seizures and lethality, respectively, in OF1 than in NMRI mice. Brain lindane concentrations at the moment of convulsion, measured after ED100 doses of lindane (400 and 200 mg/kg for NMRI and OF1 mice, respectively), did not differ between OF1 and NMRI mice, suggesting that the different potency of lindane between these mouse lines is a consequence of pharmacokinetic factors. Furthermore, (+)MK-801 antagonized seizures induced by either lindane, PTX or PTZ with similar potencies in both mouse lines. These results, coupled with the different pharmacokinetics of lindane in OF1 and NMRI mice, suggest that the distinct effects of lindane in these mice are not mediated by different activities at either NMDA or GABAA receptor complexes. Nonetheless, nifedipine antagonized lindane-induced seizures with a three-fold higher potency in NMRI than in OF1 mice. In contrast, nifedipine failed to antagonize PTX and PTZ convulsions in both OF1 and NMRI mice. These results suggest that besides the GABAA receptor complex other mechanisms related to calcium mobilization may be involved in the convulsant action of lindane."} {"id": "PMID:1280524", "title": "Senile plaques in cerebral amyloid angiopathy show accumulation of amyloid precursor protein without cytoskeletal abnormalities.", "content": "The abnormal neurites that surround beta-amyloid in senile plaques (SP) in Alzheimer disease contain beta-amyloid precursor protein (beta APP) or abnormal filaments which react with antibodies to tau. Occasionally, beta APP and abnormal filaments are present in the same neurite. Whether both types of abnormal neurites are reactive to the presence of beta-amyloid or they are instead independent from each other is unknown. To begin to clarify this issue, we comparatively studied beta APP and tau-epitopes in SP from cases of classical Alzheimer disease and cases of cerebral amyloid angiopathy, with SP but without neurofibrillary pathology. In subjects with cerebral amyloid angiopathy, about one-third of SP, the same percentage as in Alzheimer disease, were beta APP reactive in the absence of tau-reactivity. beta APP epitopes were ultrastructurally localized in dense bodies of probable lysosomal origin, adjacent to the core of SP. These results demonstrate that beta APP and tau-reactive cytoskeletal alterations occur independently in the neurites of SP. The presence of beta APP in dystrophic neurites of SP and the localization of beta APP in lysosomes suggest that beta APP containing dystrophic neurites may play a role in the extracellular deposition of amyloid.", "contents": "Senile plaques in cerebral amyloid angiopathy show accumulation of amyloid precursor protein without cytoskeletal abnormalities. The abnormal neurites that surround beta-amyloid in senile plaques (SP) in Alzheimer disease contain beta-amyloid precursor protein (beta APP) or abnormal filaments which react with antibodies to tau. Occasionally, beta APP and abnormal filaments are present in the same neurite. Whether both types of abnormal neurites are reactive to the presence of beta-amyloid or they are instead independent from each other is unknown. To begin to clarify this issue, we comparatively studied beta APP and tau-epitopes in SP from cases of classical Alzheimer disease and cases of cerebral amyloid angiopathy, with SP but without neurofibrillary pathology. In subjects with cerebral amyloid angiopathy, about one-third of SP, the same percentage as in Alzheimer disease, were beta APP reactive in the absence of tau-reactivity. beta APP epitopes were ultrastructurally localized in dense bodies of probable lysosomal origin, adjacent to the core of SP. These results demonstrate that beta APP and tau-reactive cytoskeletal alterations occur independently in the neurites of SP. The presence of beta APP in dystrophic neurites of SP and the localization of beta APP in lysosomes suggest that beta APP containing dystrophic neurites may play a role in the extracellular deposition of amyloid."} {"id": "PMID:1280525", "title": "Preferential activation of [3H]phorbol-12,13-dibutyrate binding by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) in neonatal striatal cell cultures.", "content": "Activation of excitatory amino acid receptors increased [3H]phorbol-12,13-dibutyrate ([3H]PdBu) binding in four week cultures of striatal cells from postnatal day 7 rat pups (PN7), and in PN7 cells co-cultured the fourth week with striatal cells from postnatal day 1 rat pups. Kainate (KA), trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), and N-methyl-D-aspartate (NMDA) increased [3H]PdBu binding equally in both types of cultures, but alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) increased binding by 3-fold in the co-cultures. Thus, [3H]PdBu binding in these two types of striatal cultures offers a simple model system for studying the regulation of AMPA/KA receptor responses.", "contents": "Preferential activation of [3H]phorbol-12,13-dibutyrate binding by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) in neonatal striatal cell cultures. Activation of excitatory amino acid receptors increased [3H]phorbol-12,13-dibutyrate ([3H]PdBu) binding in four week cultures of striatal cells from postnatal day 7 rat pups (PN7), and in PN7 cells co-cultured the fourth week with striatal cells from postnatal day 1 rat pups. Kainate (KA), trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD), and N-methyl-D-aspartate (NMDA) increased [3H]PdBu binding equally in both types of cultures, but alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) increased binding by 3-fold in the co-cultures. Thus, [3H]PdBu binding in these two types of striatal cultures offers a simple model system for studying the regulation of AMPA/KA receptor responses."} {"id": "PMID:1280526", "title": "A selective and extremely potent antagonist of the neurokinin-1 receptor.", "content": "Sendide [Tyr6,D-Phe7,D-His9]-substance P(6-11) has been examined by measurements of ligand binding to crude membrane fractions and by functional tests on the spinally mediated behavioral response. Sendide potently displaced [3H]-labeled substance P (SP) binding to mouse spinal cord membranes in a competitive manner. In vivo, sendide, intrathecally co-injected with SP, competitively antagonized SP-induced scratching, biting and licking. The behaviors elicited by physalaemin, septide and [Sar9, Met(O2)11]-SP were also reduced by co-administration of sendide. Large doses of sendide were needed to reduce the action of neurokinin A, D-septide, neurokinin B and eledoisin. The in vitro and in vivo pharmacological profile of sendide demonstrated that it is a selective and extremely potent antagonist of the neurokinin-1 receptor.", "contents": "A selective and extremely potent antagonist of the neurokinin-1 receptor. Sendide [Tyr6,D-Phe7,D-His9]-substance P(6-11) has been examined by measurements of ligand binding to crude membrane fractions and by functional tests on the spinally mediated behavioral response. Sendide potently displaced [3H]-labeled substance P (SP) binding to mouse spinal cord membranes in a competitive manner. In vivo, sendide, intrathecally co-injected with SP, competitively antagonized SP-induced scratching, biting and licking. The behaviors elicited by physalaemin, septide and [Sar9, Met(O2)11]-SP were also reduced by co-administration of sendide. Large doses of sendide were needed to reduce the action of neurokinin A, D-septide, neurokinin B and eledoisin. The in vitro and in vivo pharmacological profile of sendide demonstrated that it is a selective and extremely potent antagonist of the neurokinin-1 receptor."} {"id": "PMID:1280527", "title": "Ultrastructural examination of enkephalin and substance P input to cholinergic neurons within the rat neostriatum.", "content": "Enkephalin and substance P-containing inputs to cholinergic perikarya were examined in the rat neostriatum using an ultrastructural immunocytochemical double-labeling protocol. Sections of rat neostriatum were double-labeled for either choline acetyltransferase (ChAT) and substance P or ChAT and enkephalin using silver intensified colloidal gold and peroxidase as labels. Regions containing both ChAT-positive neurons and peroxidase reaction product were identified in the light microscope prior to sectioning for electron microscopy. Substance P-containing terminals which contained round synaptic vesicles and made symmetrical synaptic contacts were commonly observed in the neostriatum. Substance P synapses onto ChAT-positive perikarya and dendrites were frequently observed: up to 5 synaptic contacts were observed onto a ChAT-positive dendrite. Enkephalin labeling was also seen in a population of axon terminals containing round synaptic vesicles and exhibiting symmetrical synaptic specializations. In contrast to substance P-containing terminals, relatively few synaptic contacts were observed onto ChAT-positive labeled perikarya and dendrites although enkephalin-labeled terminals were seen in frequent contact with perikarya and dendrites of unlabeled spiny neurons. Since enkephalin and substance P are contained within different populations of striatal spiny neurons, the results of the present study suggest that these two types of neurons differ in their intrinsic striatal connections.", "contents": "Ultrastructural examination of enkephalin and substance P input to cholinergic neurons within the rat neostriatum. Enkephalin and substance P-containing inputs to cholinergic perikarya were examined in the rat neostriatum using an ultrastructural immunocytochemical double-labeling protocol. Sections of rat neostriatum were double-labeled for either choline acetyltransferase (ChAT) and substance P or ChAT and enkephalin using silver intensified colloidal gold and peroxidase as labels. Regions containing both ChAT-positive neurons and peroxidase reaction product were identified in the light microscope prior to sectioning for electron microscopy. Substance P-containing terminals which contained round synaptic vesicles and made symmetrical synaptic contacts were commonly observed in the neostriatum. Substance P synapses onto ChAT-positive perikarya and dendrites were frequently observed: up to 5 synaptic contacts were observed onto a ChAT-positive dendrite. Enkephalin labeling was also seen in a population of axon terminals containing round synaptic vesicles and exhibiting symmetrical synaptic specializations. In contrast to substance P-containing terminals, relatively few synaptic contacts were observed onto ChAT-positive labeled perikarya and dendrites although enkephalin-labeled terminals were seen in frequent contact with perikarya and dendrites of unlabeled spiny neurons. Since enkephalin and substance P are contained within different populations of striatal spiny neurons, the results of the present study suggest that these two types of neurons differ in their intrinsic striatal connections."} {"id": "PMID:1280528", "title": "A new co-culture method utilizing a dual compartment cell-allocation apparatus for observation and identification of synapse formation in vitro.", "content": "A new co-culture method for observation and identification of synapse formation utilizing dissociated retinal and tectal neurons from 7-day-old chick embryos was developed using a glass apparatus which we named 'Dual Compartment Cell-Allocation Apparatus.' This apparatus enabled us to culture these two types of cells by forming two parallel lanes, each with a dimension of 200 microns by 15 mm and with an interval of 200 microns separating the two lanes, on a collagen-coated cover slip. Infiltration and/or migration of retinal cells into the tectal cell lane was minimal with only 0.15% identified and confirmed with the fluorescence-dye labeling method. Growth of neurites connecting the two lanes was observed within 48 h of culture in a serum-free medium. Double-immunostaining of the culture preparations with anti-neurofilament and anti-synaptophysin antibodies revealed the presence of synaptophysin-hot spots on neurofilament-positive processes connecting the retinal neurons with the tectal neurons, thus confirming the formation of synapses between the neurons of the retinal lane and the neurons of the tectal lane. The dual compartment cell-allocation apparatus has proven itself to be advantageous and useful for studying the formation of synapses between two types of neurons from different origin.", "contents": "A new co-culture method utilizing a dual compartment cell-allocation apparatus for observation and identification of synapse formation in vitro. A new co-culture method for observation and identification of synapse formation utilizing dissociated retinal and tectal neurons from 7-day-old chick embryos was developed using a glass apparatus which we named 'Dual Compartment Cell-Allocation Apparatus.' This apparatus enabled us to culture these two types of cells by forming two parallel lanes, each with a dimension of 200 microns by 15 mm and with an interval of 200 microns separating the two lanes, on a collagen-coated cover slip. Infiltration and/or migration of retinal cells into the tectal cell lane was minimal with only 0.15% identified and confirmed with the fluorescence-dye labeling method. Growth of neurites connecting the two lanes was observed within 48 h of culture in a serum-free medium. Double-immunostaining of the culture preparations with anti-neurofilament and anti-synaptophysin antibodies revealed the presence of synaptophysin-hot spots on neurofilament-positive processes connecting the retinal neurons with the tectal neurons, thus confirming the formation of synapses between the neurons of the retinal lane and the neurons of the tectal lane. The dual compartment cell-allocation apparatus has proven itself to be advantageous and useful for studying the formation of synapses between two types of neurons from different origin."} {"id": "PMID:1280529", "title": "Dextromethorphan antagonizes the acute depletion of brain serotonin by p-chloroamphetamine and H75/12 in rats.", "content": "A role for calcium in p-chloroamphetamine-induced neurotoxicity has been inferred previously from protective effects of dextromethorphan. We found that dextromethorphan reduces rat brain concentrations of 5-hydroxyindoleacetic acid and blocks the acute, non-neurotoxic depletion of brain serotonin by p-chloroamphetamine and by H75/12. Inhibition of the membrane transporter on brain serotonin neurons by dextromethorphan in vivo might explain its protective effect against p-chloroamphetamine neurotoxicity.", "contents": "Dextromethorphan antagonizes the acute depletion of brain serotonin by p-chloroamphetamine and H75/12 in rats. A role for calcium in p-chloroamphetamine-induced neurotoxicity has been inferred previously from protective effects of dextromethorphan. We found that dextromethorphan reduces rat brain concentrations of 5-hydroxyindoleacetic acid and blocks the acute, non-neurotoxic depletion of brain serotonin by p-chloroamphetamine and by H75/12. Inhibition of the membrane transporter on brain serotonin neurons by dextromethorphan in vivo might explain its protective effect against p-chloroamphetamine neurotoxicity."} {"id": "PMID:1280530", "title": "Organization of layers II-III connections in human visual cortex revealed by in vitro injections of biocytin.", "content": "In the search for cortical mechanisms subserving psychological phenomena, a better understanding of human cortical circuitry is crucial. In this report we describe aspects of intrinsic connectivity of supragranular layers in human visual cortex, revealed by extracellular injections of the anterograde tracer biocytin in vitro. Human cortical slices were obtained from visual association cortex in the posterior-medial portion of the dorsal bank of the occipital lobe, removed during neurosurgical tumor ablations. Small iontophoretic injections of biocytin into layers II-III revealed intense Golgi-like staining of axonal projections emanating from the injection sites. Vertically descending axons are grouped in bundles 20 microns in diameter which are spaced 15 microns apart. Some of these axons enter the white matter and send long oblique and horizontal collaterals. The main horizontal spread of the axons could be observed in layers II-III and V. The bulk of projections extends to a distance of 1.5 mm in layers II-III and 1.1 mm in layer V. Few individual axons could be observed at greater distances. In contrast, layer IV is almost devoid of horizontal connections, forming a clear gap between supra- and infragranular layers. Axon collaterals in the infragranular layers project mostly in a descending oblique direction with long horizontal collaterals in lower layer VI.", "contents": "Organization of layers II-III connections in human visual cortex revealed by in vitro injections of biocytin. In the search for cortical mechanisms subserving psychological phenomena, a better understanding of human cortical circuitry is crucial. In this report we describe aspects of intrinsic connectivity of supragranular layers in human visual cortex, revealed by extracellular injections of the anterograde tracer biocytin in vitro. Human cortical slices were obtained from visual association cortex in the posterior-medial portion of the dorsal bank of the occipital lobe, removed during neurosurgical tumor ablations. Small iontophoretic injections of biocytin into layers II-III revealed intense Golgi-like staining of axonal projections emanating from the injection sites. Vertically descending axons are grouped in bundles 20 microns in diameter which are spaced 15 microns apart. Some of these axons enter the white matter and send long oblique and horizontal collaterals. The main horizontal spread of the axons could be observed in layers II-III and V. The bulk of projections extends to a distance of 1.5 mm in layers II-III and 1.1 mm in layer V. Few individual axons could be observed at greater distances. In contrast, layer IV is almost devoid of horizontal connections, forming a clear gap between supra- and infragranular layers. Axon collaterals in the infragranular layers project mostly in a descending oblique direction with long horizontal collaterals in lower layer VI."} {"id": "PMID:1280531", "title": "Failure of anticytokeratin 18 antibody to improve flow cytometric detection of bladder cancer.", "content": "Bladder washing specimens containing inflammatory or squamous cells have been difficult to accurately analyze with single-parameter DNA flow cytometric (FCM) methods. The anticytokeratin 18 antibody, CK5, was used in a multiparameter assay of 275 bladder washing and voided urine specimens to immunoselect only the bladder transitional cells for DNA analysis. Flow cytometric detection of transitional cell carcinoma was increased by immunoselection of CK5-positive cells in specimens from patients with disease. Unfortunately, a similar increase in hyperdiploid cells in pathologically benign specimens was observed, which resulted in a false-positive rate of 45%. In some instances, multiparameter FCM assays with CK5 could detect aneuploid cell populations not clearly evident by single-parameter analysis. However, the results from this study of the hyperdiploid cell fraction showed that the increased sensitivity resulting from the use of CK5 was not clinically useful because of the decrease in specificity.", "contents": "Failure of anticytokeratin 18 antibody to improve flow cytometric detection of bladder cancer. Bladder washing specimens containing inflammatory or squamous cells have been difficult to accurately analyze with single-parameter DNA flow cytometric (FCM) methods. The anticytokeratin 18 antibody, CK5, was used in a multiparameter assay of 275 bladder washing and voided urine specimens to immunoselect only the bladder transitional cells for DNA analysis. Flow cytometric detection of transitional cell carcinoma was increased by immunoselection of CK5-positive cells in specimens from patients with disease. Unfortunately, a similar increase in hyperdiploid cells in pathologically benign specimens was observed, which resulted in a false-positive rate of 45%. In some instances, multiparameter FCM assays with CK5 could detect aneuploid cell populations not clearly evident by single-parameter analysis. However, the results from this study of the hyperdiploid cell fraction showed that the increased sensitivity resulting from the use of CK5 was not clinically useful because of the decrease in specificity."} {"id": "PMID:1280532", "title": "Changes in ventricular 1,2-diacylglycerol content in rats following monocrotaline treatment.", "content": "1,2-Diacylglycerol may initiate cardiac hypertrophy, probably by activating protein kinase C. To test this hypothesis we determined the 1,2-diacylglycerol content of hypertrophied tissue. Rats were treated with monocrotaline and developed severe right ventricular hypertrophy followed by congestive heart failure. 1,2-Diacylglycerol content and fatty acid composition, DNA concentrations, and RNA concentrations in the right ventricle from monocrotaline treated rats were compared with values obtained from the left side or from control rats. During the first week, the right ventricle showed no significant change in 1,2-diacylglycerol content and a small increase in RNA concentration. However, the 1,2-diacylglycerol content was significantly increased by 55% at two weeks after monocrotaline injection, when DNA and RNA synthesis was also enhanced to its highest level when compared with control rats (37% and 18%, respectively). At four weeks after monocrotaline injection, conversely, the 1,2-diacylglycerol content was decreased by 25% in the right ventricle from monocrotaline treated rats, most of which had pleural and peritoneal effusions indicating congestive heart failure, although RNA synthesis was sustained at a high level. The fatty acid composition of 1,2-diacylglycerol did not differ significantly between the right and left ventricles or control rat ventricles. These results suggest that 1,2-diacylglycerol accumulation is associated with development of hypertrophy in monocrotaline treated rats. In contrast, at a stage of congestive heart failure 1,2-diacylglycerol production decreased, suggesting that intracellular transduction mechanisms may be attenuated.", "contents": "Changes in ventricular 1,2-diacylglycerol content in rats following monocrotaline treatment. 1,2-Diacylglycerol may initiate cardiac hypertrophy, probably by activating protein kinase C. To test this hypothesis we determined the 1,2-diacylglycerol content of hypertrophied tissue. Rats were treated with monocrotaline and developed severe right ventricular hypertrophy followed by congestive heart failure. 1,2-Diacylglycerol content and fatty acid composition, DNA concentrations, and RNA concentrations in the right ventricle from monocrotaline treated rats were compared with values obtained from the left side or from control rats. During the first week, the right ventricle showed no significant change in 1,2-diacylglycerol content and a small increase in RNA concentration. However, the 1,2-diacylglycerol content was significantly increased by 55% at two weeks after monocrotaline injection, when DNA and RNA synthesis was also enhanced to its highest level when compared with control rats (37% and 18%, respectively). At four weeks after monocrotaline injection, conversely, the 1,2-diacylglycerol content was decreased by 25% in the right ventricle from monocrotaline treated rats, most of which had pleural and peritoneal effusions indicating congestive heart failure, although RNA synthesis was sustained at a high level. The fatty acid composition of 1,2-diacylglycerol did not differ significantly between the right and left ventricles or control rat ventricles. These results suggest that 1,2-diacylglycerol accumulation is associated with development of hypertrophy in monocrotaline treated rats. In contrast, at a stage of congestive heart failure 1,2-diacylglycerol production decreased, suggesting that intracellular transduction mechanisms may be attenuated."} {"id": "PMID:1280533", "title": "Prevention of experimental autoimmune encephalomyelitis in Lewis rats by treatment with an anti-rat CD5 antibody (OX19).", "content": "Treatment of Lewis rats with a single dose of OX19 antibody, specific for rat CD5, uniformly prevented the development of experimental autoimmune encephalomyelitis (EAE). This protective effect had several notable characteristics: (1) it persisted for at least 10 days; (2) it could be achieved with either high doses of the antibody (> 200 micrograms) or lower doses (100-200 micrograms), which did not deplete T cell populations; and (3) the treated animals were able to mount comparable T cell responses to both myelin basic protein and myelin-unrelated antigens. In addition, antibody treatment consistently prevented the development of adoptively transferred EAE, suggesting that enhanced suppressor cell activity may have contributed to the protection. Antibodies such as OX19 appear capable of blocking the development of EAE, and perhaps other autoimmune diseases as well.", "contents": "Prevention of experimental autoimmune encephalomyelitis in Lewis rats by treatment with an anti-rat CD5 antibody (OX19). Treatment of Lewis rats with a single dose of OX19 antibody, specific for rat CD5, uniformly prevented the development of experimental autoimmune encephalomyelitis (EAE). This protective effect had several notable characteristics: (1) it persisted for at least 10 days; (2) it could be achieved with either high doses of the antibody (> 200 micrograms) or lower doses (100-200 micrograms), which did not deplete T cell populations; and (3) the treated animals were able to mount comparable T cell responses to both myelin basic protein and myelin-unrelated antigens. In addition, antibody treatment consistently prevented the development of adoptively transferred EAE, suggesting that enhanced suppressor cell activity may have contributed to the protection. Antibodies such as OX19 appear capable of blocking the development of EAE, and perhaps other autoimmune diseases as well."} {"id": "PMID:1280534", "title": "Effect of interferon-gamma on myelin basic protein-specific T cell line proliferation in response to antigen-pulsed accessory cells.", "content": "We have shown previously that treatment of SJL/J mice with anti-interferon-gamma monoclonal antibody (mAb) exacerbated experimental allergic encephalomyelitis (EAE) only if administered at the time of encephalitogenic challenge. Here we investigate the role of interferon-gamma (IFN-gamma) and anti-IFN-gamma mAb in the early events of T cell activation in vitro. Pretreatment of murine peritoneal exudate cells (PEC) with IFN-gamma led to a significant increase in their ability to activate myelin basic protein (MBP)-specific, short-term T cell lines. When exogenous IFN-gamma was added to cocultures of T cells and MBP-pulsed PEC, the antigen-specific T cell proliferation was considerably reduced. Anti-IFN-gamma mAb added to these cultures neutralized the inhibitory effect of the exogenous IFN-gamma on T cell proliferation but had no visible effect on class II MHC expression by the antigen-pulsed PEC present in the same cultures. A reduction in T cell proliferation was also observed when the T cells were treated with IFN-gamma prior to coculture with the MBP-pulsed PEC. These results demonstrate that, on one hand, IFN-gamma enhances the ability of PEC to induce antigen-specific T cell proliferation but, on the other hand, acts on the T cells themselves by inhibiting their proliferation in response to the antigen-pulsed PEC. This may explain why treatment with anti-IFN-gamma antibody in vivo induces EAE exacerbation.", "contents": "Effect of interferon-gamma on myelin basic protein-specific T cell line proliferation in response to antigen-pulsed accessory cells. We have shown previously that treatment of SJL/J mice with anti-interferon-gamma monoclonal antibody (mAb) exacerbated experimental allergic encephalomyelitis (EAE) only if administered at the time of encephalitogenic challenge. Here we investigate the role of interferon-gamma (IFN-gamma) and anti-IFN-gamma mAb in the early events of T cell activation in vitro. Pretreatment of murine peritoneal exudate cells (PEC) with IFN-gamma led to a significant increase in their ability to activate myelin basic protein (MBP)-specific, short-term T cell lines. When exogenous IFN-gamma was added to cocultures of T cells and MBP-pulsed PEC, the antigen-specific T cell proliferation was considerably reduced. Anti-IFN-gamma mAb added to these cultures neutralized the inhibitory effect of the exogenous IFN-gamma on T cell proliferation but had no visible effect on class II MHC expression by the antigen-pulsed PEC present in the same cultures. A reduction in T cell proliferation was also observed when the T cells were treated with IFN-gamma prior to coculture with the MBP-pulsed PEC. These results demonstrate that, on one hand, IFN-gamma enhances the ability of PEC to induce antigen-specific T cell proliferation but, on the other hand, acts on the T cells themselves by inhibiting their proliferation in response to the antigen-pulsed PEC. This may explain why treatment with anti-IFN-gamma antibody in vivo induces EAE exacerbation."} {"id": "PMID:1280535", "title": "Anaesthetic implications of 32% Dextran-70 (Hyskon) during hysteroscopy: hysteroscopy syndrome.", "content": "This review describes the properties and side effects of Hyskon and the implications for the patient and anaesthetist during hysteroscopy. The amount of Hyskon absorbed is dependent on the injection pressure, the extent of tissue trauma, the seal of the hysteroscope around the cervix, and the duration of infusion. The mechanism of pulmonary oedema after absorbtion of Hyskon is fluid overload, and not injury to pulmonary capillary endothelium. The haematological effects are primarily due to haemodilution. However, case reports suggest that Dextran 70 may cause a syndrome resembling disseminated intravascular coagulation. The allergic response to Hyskon consists of both an anaphylactic and an anaphylactoid component. It is recommended that hysteroscopy with Hyskon be limited to 45 min, and that all possible measures be taken to minimize tissue trauma and bleeding. The volume of Hyskon should be limited to less than 500 ml, since pulmonary oedema and coagulopathy have been described with even lesser amounts. The cumulative volume of Hyskon should be monitored frequently and the patient should be closely monitored for signs of impending pulmonary oedema.", "contents": "Anaesthetic implications of 32% Dextran-70 (Hyskon) during hysteroscopy: hysteroscopy syndrome. This review describes the properties and side effects of Hyskon and the implications for the patient and anaesthetist during hysteroscopy. The amount of Hyskon absorbed is dependent on the injection pressure, the extent of tissue trauma, the seal of the hysteroscope around the cervix, and the duration of infusion. The mechanism of pulmonary oedema after absorbtion of Hyskon is fluid overload, and not injury to pulmonary capillary endothelium. The haematological effects are primarily due to haemodilution. However, case reports suggest that Dextran 70 may cause a syndrome resembling disseminated intravascular coagulation. The allergic response to Hyskon consists of both an anaphylactic and an anaphylactoid component. It is recommended that hysteroscopy with Hyskon be limited to 45 min, and that all possible measures be taken to minimize tissue trauma and bleeding. The volume of Hyskon should be limited to less than 500 ml, since pulmonary oedema and coagulopathy have been described with even lesser amounts. The cumulative volume of Hyskon should be monitored frequently and the patient should be closely monitored for signs of impending pulmonary oedema."} {"id": "PMID:1280536", "title": "Lack of evidence for a high-affinity sarcosinamide carrier or a catecholamine carrier in Calu-1 lung-cancer cells, HT-29 colon-cancer cells, and DHF fibroblasts.", "content": "We have previously demonstrated that uptake of the amino acid amide sarcosinamide by the glioma cell line SK-MG-1 occurs via the catecholamine carrier that accommodates epinephrine (Km = 0.284 mM; Vmax = 0.154 nmol/10(6) cells/min). Sarcosinamide chloroethylnitrosourea (SarCNU), a new anticancer agent that exerts increased in vitro antitumor activity against gliomas as compared with BCNU (bis-chloroethylnitrosourea), the standard agent of choice, competitively inhibits sarcosinamide uptake by SK-MG-1 cells [inhibition constant (Ki) = 3.26 mM]. Using radiolabeled N-[3H]-sarcosinamide, we determined the transport of sarcosinamide in HT-29 colon-cancer cells, in Calu-1 lung-cancer cells, and in normal foreskin DHF fibroblasts. Sarcosinamide transport was linear for up to 1 min at 22 degrees C. In HT-29 cells and DHF fibroblasts, the uptake of sarcosinamide followed Michaelis-Menten kinetics of carrier-mediated transport. In HT-29 cells the Michaelis constant (Km) was 2.76 +/- 0.1 mM and the maximal velocity (Vmax) was 2.03 +/- 0.1 nmol/10(6) cells/min, whereas in DHF fibroblasts the respective values were 6.58 +/- 3.90 mM and 12.08 +/- 8.20 nmol/10(6) cells/min. In these two cell lines, neither epinephrine nor leucine significantly reduced sarcosinamide transport. In Calu-1 cells there was no evidence of carrier-mediated transport of either sarcosinamide or epinephrine. These nonglial cell lines lack a high-affinity catecholamine carrier. The increased cytotoxicity of SarCNU in gliomas may correlate with the presence of a high-affinity catecholamine carrier.", "contents": "Lack of evidence for a high-affinity sarcosinamide carrier or a catecholamine carrier in Calu-1 lung-cancer cells, HT-29 colon-cancer cells, and DHF fibroblasts. We have previously demonstrated that uptake of the amino acid amide sarcosinamide by the glioma cell line SK-MG-1 occurs via the catecholamine carrier that accommodates epinephrine (Km = 0.284 mM; Vmax = 0.154 nmol/10(6) cells/min). Sarcosinamide chloroethylnitrosourea (SarCNU), a new anticancer agent that exerts increased in vitro antitumor activity against gliomas as compared with BCNU (bis-chloroethylnitrosourea), the standard agent of choice, competitively inhibits sarcosinamide uptake by SK-MG-1 cells [inhibition constant (Ki) = 3.26 mM]. Using radiolabeled N-[3H]-sarcosinamide, we determined the transport of sarcosinamide in HT-29 colon-cancer cells, in Calu-1 lung-cancer cells, and in normal foreskin DHF fibroblasts. Sarcosinamide transport was linear for up to 1 min at 22 degrees C. In HT-29 cells and DHF fibroblasts, the uptake of sarcosinamide followed Michaelis-Menten kinetics of carrier-mediated transport. In HT-29 cells the Michaelis constant (Km) was 2.76 +/- 0.1 mM and the maximal velocity (Vmax) was 2.03 +/- 0.1 nmol/10(6) cells/min, whereas in DHF fibroblasts the respective values were 6.58 +/- 3.90 mM and 12.08 +/- 8.20 nmol/10(6) cells/min. In these two cell lines, neither epinephrine nor leucine significantly reduced sarcosinamide transport. In Calu-1 cells there was no evidence of carrier-mediated transport of either sarcosinamide or epinephrine. These nonglial cell lines lack a high-affinity catecholamine carrier. The increased cytotoxicity of SarCNU in gliomas may correlate with the presence of a high-affinity catecholamine carrier."} {"id": "PMID:1280537", "title": "Phase II study of cisplatin as a 5-day continuous infusion with vindesine plus recombinant human granulocyte-colony-stimulating factor in the treatment of advanced non-small-cell lung cancer.", "content": "A total of 36 patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of 5-day continuous i.v. infusion of cisplatin (25 mg/m2 daily), bolus infusion of vindesine (3 mg/m2) on days 1 and 8, and s.c. injection of recombinant human granulocyte-colony-stimulating factor (2 micrograms/kg daily) on days 6-21. Treatment was repeated every 3-4 weeks. Responding patients with stage IIIA or IIIB disease received chest radiation therapy (50-60 Gy) after this treatment. One complete response and 23 partial responses were observed, for an overall response rate of 66.7% (24/36; 95% confidence limits, 51.3%-82.1%). The median duration of response was 5.7 months and the median overall survival was 10.1 months. WHO grade 3 or 4 leukopenia and neutropenia occurred in 22 (61%) and 27 (75%) patients, respectively, but the mean duration of leukopenia (< 2,000/mm3) and neutropenia (< 1,000/mm3) was 3.4 and 3.5 days, respectively, and there was no instance of life-threatening infection. Thrombocytopenia and anemia of grade 3 or 4 occurred in 28% and 36% of our subjects, respectively. Grade 2 nausea and vomiting occurred in 47% of the patients. Elevated serum creatinine levels (> 1.5 mg/dl) were observed in 3 (8%) of the 36 patients. One patient died of acute renal failure induced by hemorrhage of a gastric ulcer. This regimen is effective in the treatment of NSCLC and further studies of this combination are warranted.", "contents": "Phase II study of cisplatin as a 5-day continuous infusion with vindesine plus recombinant human granulocyte-colony-stimulating factor in the treatment of advanced non-small-cell lung cancer. A total of 36 patients with advanced non-small-cell lung cancer (NSCLC) were treated with a combination of 5-day continuous i.v. infusion of cisplatin (25 mg/m2 daily), bolus infusion of vindesine (3 mg/m2) on days 1 and 8, and s.c. injection of recombinant human granulocyte-colony-stimulating factor (2 micrograms/kg daily) on days 6-21. Treatment was repeated every 3-4 weeks. Responding patients with stage IIIA or IIIB disease received chest radiation therapy (50-60 Gy) after this treatment. One complete response and 23 partial responses were observed, for an overall response rate of 66.7% (24/36; 95% confidence limits, 51.3%-82.1%). The median duration of response was 5.7 months and the median overall survival was 10.1 months. WHO grade 3 or 4 leukopenia and neutropenia occurred in 22 (61%) and 27 (75%) patients, respectively, but the mean duration of leukopenia (< 2,000/mm3) and neutropenia (< 1,000/mm3) was 3.4 and 3.5 days, respectively, and there was no instance of life-threatening infection. Thrombocytopenia and anemia of grade 3 or 4 occurred in 28% and 36% of our subjects, respectively. Grade 2 nausea and vomiting occurred in 47% of the patients. Elevated serum creatinine levels (> 1.5 mg/dl) were observed in 3 (8%) of the 36 patients. One patient died of acute renal failure induced by hemorrhage of a gastric ulcer. This regimen is effective in the treatment of NSCLC and further studies of this combination are warranted."} {"id": "PMID:1280538", "title": "Blighted ovum: ultrasonic, histopathologic and hormonal considerations.", "content": "Thirty women experiencing early pregnancy failure (blighted ovum) were studied at frequent intervals with serial measurements of serum human chorionic gonadotropin (beta-hCG), progesterone (P4) and estradiol (E2). The diagnosis of blighted ovum had previously been made by careful ultrasonic examination (s). Histopathologic findings in the placenta were studied in all cases. Hormonal levels were variable and in most of the cases indistinguishable from normal pregnancies. In only 50% of the cases the histopathologic examination revealed findings compatible for the blighted ovum criteria.", "contents": "Blighted ovum: ultrasonic, histopathologic and hormonal considerations. Thirty women experiencing early pregnancy failure (blighted ovum) were studied at frequent intervals with serial measurements of serum human chorionic gonadotropin (beta-hCG), progesterone (P4) and estradiol (E2). The diagnosis of blighted ovum had previously been made by careful ultrasonic examination (s). Histopathologic findings in the placenta were studied in all cases. Hormonal levels were variable and in most of the cases indistinguishable from normal pregnancies. In only 50% of the cases the histopathologic examination revealed findings compatible for the blighted ovum criteria."} {"id": "PMID:1280539", "title": "Amniotic fluid hormone profiles during normal and abnormal pregnancy.", "content": "Amniotic fluid (AF) and maternal serum (MS) chorionic gonadotropin (HCG), placental lactogen (HPL), pregnancy-specific beta 1-glycoprotein (SP1), total estrogens (ET), alpha-fetoprotein (AFP) and prolactin (PRL) were measured by enzyme-immunoassays, in 50 normal (A) and in 37 abnormal (B) pregnancies, from 16th to 40th weeks. A: the proteins HCG, AFP and PRL showed a similar decreasing trend after the 20th week, while HPL and SP1 rose progressively throughout the 2nd trimester, thereafter remaining constant. On the contrary ET showed an increasing pattern until term. Chorionic gonadotropin HPL and SP1 in MS were higher than in AF, while AF values of AFP and PRL were higher than in MS, but the ratio MS/AF of all hormone values increased significantly from the 2nd to the 3rd trimester (p < 0.005-p < 0.000001). Estrogens had about the same concentration in AF and MS during the 2nd trimester, but at term of pregnancy, their AF values were double those of MS. B: in polyhydramnios, elevated AF placental hormones were found, while PRL was very low. In erythroblastosis and diabetes, AFP was very low, but placental hormones, PRL and ET were both high and low. In toxemia, SP1, hCG and PRL were elevated, while HPL and ET were very low. In anencephaly and hydrocephaly with spina bifida, AFP was markedly elevated and ET were very low, but in simple hydrocephalus, very low AFP was found. In chromosomal anomalies very high placental hormones and very low AFP and ET were found.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Amniotic fluid hormone profiles during normal and abnormal pregnancy. Amniotic fluid (AF) and maternal serum (MS) chorionic gonadotropin (HCG), placental lactogen (HPL), pregnancy-specific beta 1-glycoprotein (SP1), total estrogens (ET), alpha-fetoprotein (AFP) and prolactin (PRL) were measured by enzyme-immunoassays, in 50 normal (A) and in 37 abnormal (B) pregnancies, from 16th to 40th weeks. A: the proteins HCG, AFP and PRL showed a similar decreasing trend after the 20th week, while HPL and SP1 rose progressively throughout the 2nd trimester, thereafter remaining constant. On the contrary ET showed an increasing pattern until term. Chorionic gonadotropin HPL and SP1 in MS were higher than in AF, while AF values of AFP and PRL were higher than in MS, but the ratio MS/AF of all hormone values increased significantly from the 2nd to the 3rd trimester (p < 0.005-p < 0.000001). Estrogens had about the same concentration in AF and MS during the 2nd trimester, but at term of pregnancy, their AF values were double those of MS. B: in polyhydramnios, elevated AF placental hormones were found, while PRL was very low. In erythroblastosis and diabetes, AFP was very low, but placental hormones, PRL and ET were both high and low. In toxemia, SP1, hCG and PRL were elevated, while HPL and ET were very low. In anencephaly and hydrocephaly with spina bifida, AFP was markedly elevated and ET were very low, but in simple hydrocephalus, very low AFP was found. In chromosomal anomalies very high placental hormones and very low AFP and ET were found.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280540", "title": "An unusual T-cell surface phenotype in vivo correlates with the failure to proliferate and produce IL-2 in vitro in a patient with common variable immunodeficiency.", "content": "Stimulation of T-lymphocytes derived from some patients with common variable immunodeficiency (CVID) syndrome results in defective proliferation. The underlying mechanism is related to the inability of stimulated cells to secrete IL-2 while the expression of IL-2 receptor (IL-2R) is normal. We have identified a patient whose peripheral T-cells failed to proliferate and secrete IL-2 upon stimulation. The addition of recombinant IL-2 restored proliferation. The defect did not seem to be caused by accessory cell failure since the patient's adherent cells produced IL-1 and IL-6, and addition of allogeneic irradiated cells did not induce proliferation. Stimulation of CVID T-cells with phorbol esters and Ca2+ ionophore induced both IL-2 secretion and proliferation, indicating the absence of a defect in the transcription and/or translation of the IL-2 gene. The patient's T-cells expressed high levels of CD3. The majority of T-cells expressed the CD38 molecule which is normally found on thymocytes or activated T-cells but not peripheral blood T-cells and HLA-DR, another activation marker. However, CD25 (the IL-2R) and CD1, a marker of more immature thymocytes, were not expressed. Finally, the patient's cells were sensitive to an in vitro corticosteroid treatment. The possibilities that this patient's T-cells represent anergic T-cells or not fully matured thymocytes are discussed.", "contents": "An unusual T-cell surface phenotype in vivo correlates with the failure to proliferate and produce IL-2 in vitro in a patient with common variable immunodeficiency. Stimulation of T-lymphocytes derived from some patients with common variable immunodeficiency (CVID) syndrome results in defective proliferation. The underlying mechanism is related to the inability of stimulated cells to secrete IL-2 while the expression of IL-2 receptor (IL-2R) is normal. We have identified a patient whose peripheral T-cells failed to proliferate and secrete IL-2 upon stimulation. The addition of recombinant IL-2 restored proliferation. The defect did not seem to be caused by accessory cell failure since the patient's adherent cells produced IL-1 and IL-6, and addition of allogeneic irradiated cells did not induce proliferation. Stimulation of CVID T-cells with phorbol esters and Ca2+ ionophore induced both IL-2 secretion and proliferation, indicating the absence of a defect in the transcription and/or translation of the IL-2 gene. The patient's T-cells expressed high levels of CD3. The majority of T-cells expressed the CD38 molecule which is normally found on thymocytes or activated T-cells but not peripheral blood T-cells and HLA-DR, another activation marker. However, CD25 (the IL-2R) and CD1, a marker of more immature thymocytes, were not expressed. Finally, the patient's cells were sensitive to an in vitro corticosteroid treatment. The possibilities that this patient's T-cells represent anergic T-cells or not fully matured thymocytes are discussed."} {"id": "PMID:1280541", "title": "Mapping of the immunoreactive domains of a small nuclear ribonucleoprotein-associated Sm-D autoantigen.", "content": "The Sm-D(D1) small nuclear ribonucleoprotein (snRNP) polypeptide is a major target of autoantibodies diagnostic for systemic lupus erythematosus. The cDNA encoding the protein from Raji cells was expressed in Escherichia coli as a fusion protein with anthranilate synthase (TrpE-Sm-D). When tested by protein blot, the recombinant polypeptide was strongly immunoreactive under defined blotting conditions, which appear to facilitate the refolding of the polypeptide into a native conformation. Multiple translational fusions between the trpE gene and fragments encompassing the length of the Sm-D coding sequence were constructed for epitope mapping. The results describe two general patterns of anti-Sm reactivity: (i) antibodies that recognize only the full-length antigen and are presumably directed against discontinuous epitopes, and (ii) antibodies that recognize the carboxy terminus of the antigen which embodies an extended/charged structure.", "contents": "Mapping of the immunoreactive domains of a small nuclear ribonucleoprotein-associated Sm-D autoantigen. The Sm-D(D1) small nuclear ribonucleoprotein (snRNP) polypeptide is a major target of autoantibodies diagnostic for systemic lupus erythematosus. The cDNA encoding the protein from Raji cells was expressed in Escherichia coli as a fusion protein with anthranilate synthase (TrpE-Sm-D). When tested by protein blot, the recombinant polypeptide was strongly immunoreactive under defined blotting conditions, which appear to facilitate the refolding of the polypeptide into a native conformation. Multiple translational fusions between the trpE gene and fragments encompassing the length of the Sm-D coding sequence were constructed for epitope mapping. The results describe two general patterns of anti-Sm reactivity: (i) antibodies that recognize only the full-length antigen and are presumably directed against discontinuous epitopes, and (ii) antibodies that recognize the carboxy terminus of the antigen which embodies an extended/charged structure."} {"id": "PMID:1280542", "title": "Generalized inflammation during peritonitis evidenced by intracutaneous E-selectin expression.", "content": "E-selectin is a human endothelial leukocyte adhesion molecule which is expressed on endothelial cells after exposure to inflammatory mediators and which is known to be involved in the adhesion of polymorphonuclear cells to the endothelium in vitro. Data on E-selectin expression in vivo are limited. In the present report, we studied the expression of E-selectin in skin biopsies from patients with peritonitis due to a perforation of the gastrointestinal tract. Substantial E-selectin expression was observed on the vasculature of the skin from six out of eight of these severely ill patients. Skin obtained from healthy individuals stained negative, or showed a faint patchy staining in 30% of biopsies tested. These results provide evidence that E-selectin expression was induced at a distance from the primary inflammatory process on the vascular endothelium of the skin during severe peritonitis. Cutaneous E-selectin expression thus reflected on the surface of the body a state of generalized activated endothelium.", "contents": "Generalized inflammation during peritonitis evidenced by intracutaneous E-selectin expression. E-selectin is a human endothelial leukocyte adhesion molecule which is expressed on endothelial cells after exposure to inflammatory mediators and which is known to be involved in the adhesion of polymorphonuclear cells to the endothelium in vitro. Data on E-selectin expression in vivo are limited. In the present report, we studied the expression of E-selectin in skin biopsies from patients with peritonitis due to a perforation of the gastrointestinal tract. Substantial E-selectin expression was observed on the vasculature of the skin from six out of eight of these severely ill patients. Skin obtained from healthy individuals stained negative, or showed a faint patchy staining in 30% of biopsies tested. These results provide evidence that E-selectin expression was induced at a distance from the primary inflammatory process on the vascular endothelium of the skin during severe peritonitis. Cutaneous E-selectin expression thus reflected on the surface of the body a state of generalized activated endothelium."} {"id": "PMID:1280543", "title": "Hydroxyethyl starch induced acquired von Willebrand's disease.", "content": "Hydroxyethyl starch (HES) (Hespan, DuPont) is a widely used synthetic volume expander which in standard doses of up to 1.5l in 24 h has no significant effect on coagulation (Munsch et al. 1988). However, the data sheet states that in large volumes HES may alter the coagulation mechanism. We now report a case of HES induced acquired von Willebrand's disease (vWD) in which severe bleeding occurred.", "contents": "Hydroxyethyl starch induced acquired von Willebrand's disease. Hydroxyethyl starch (HES) (Hespan, DuPont) is a widely used synthetic volume expander which in standard doses of up to 1.5l in 24 h has no significant effect on coagulation (Munsch et al. 1988). However, the data sheet states that in large volumes HES may alter the coagulation mechanism. We now report a case of HES induced acquired von Willebrand's disease (vWD) in which severe bleeding occurred."} {"id": "PMID:1280544", "title": "Nucleotide sequence of the central coding region of bovine erythrotropin/insulin-like growth factor II cDNA from fetal intestine and northern analysis of the major IGF II transcripts at the time of hepatic erythropoiesis.", "content": "1. cDNA for insulin-like growth factor II (IGF II) was synthesized from poly A(+)-RNA from fetal bovine intestine and amplified. 2. The sequence corresponding to amino acids 6-62 was identical to a published ovine IGF II sequence cDNA with the exception of a single nucleotide change (G to A). 3. Northern blot analysis of intestine, liver, kidney and spleen from bovine fetuses showed multiple IGF II RNA species which are more similar to the human than to the rodent mRNAs. 4. Under the hybridization conditions used, synthesis of antisense strands, as described in embryonic chicken IGF II transcripts, was undetectable.", "contents": "Nucleotide sequence of the central coding region of bovine erythrotropin/insulin-like growth factor II cDNA from fetal intestine and northern analysis of the major IGF II transcripts at the time of hepatic erythropoiesis. 1. cDNA for insulin-like growth factor II (IGF II) was synthesized from poly A(+)-RNA from fetal bovine intestine and amplified. 2. The sequence corresponding to amino acids 6-62 was identical to a published ovine IGF II sequence cDNA with the exception of a single nucleotide change (G to A). 3. Northern blot analysis of intestine, liver, kidney and spleen from bovine fetuses showed multiple IGF II RNA species which are more similar to the human than to the rodent mRNAs. 4. Under the hybridization conditions used, synthesis of antisense strands, as described in embryonic chicken IGF II transcripts, was undetectable."} {"id": "PMID:1280545", "title": "Immunochemical characterisation of tachykinin immunoreactivity in the nervous system of the garden snail, Helix aspersa.", "content": "1. Circumoesophageal ganglia and foot muscle of the garden snail, Helix aspersa, were subjected to immunocytochemistry using antisera to the tachykinins, substance P (SP), neurokinin A (NKA), kassinin (KAS) and eledoisin (ELE). 2. Immunoreactivity in neuronal somata and fibres was detected only with the SP antiserum. 3. SP and NKA radioimmunoassays were performed on extracts of circumoesophageal ganglia. In common with immunocytochemistry, immunoreactivity was only detected with the SP antiserum. 4. Gel permeation chromatography of extracts resolved a single peak of immunoreactivity eluting slightly later than synthetic mammalian SP. Reverse-phase HPLC of immunoreactive fractions resolved two immunoreactive peptides representing oxidised and reduced forms of a single peptide. 5. These data suggest that the nervous system of H. aspersa contains a single tachykinin with C-terminal structural characteristics similar to mammalian SP.", "contents": "Immunochemical characterisation of tachykinin immunoreactivity in the nervous system of the garden snail, Helix aspersa. 1. Circumoesophageal ganglia and foot muscle of the garden snail, Helix aspersa, were subjected to immunocytochemistry using antisera to the tachykinins, substance P (SP), neurokinin A (NKA), kassinin (KAS) and eledoisin (ELE). 2. Immunoreactivity in neuronal somata and fibres was detected only with the SP antiserum. 3. SP and NKA radioimmunoassays were performed on extracts of circumoesophageal ganglia. In common with immunocytochemistry, immunoreactivity was only detected with the SP antiserum. 4. Gel permeation chromatography of extracts resolved a single peak of immunoreactivity eluting slightly later than synthetic mammalian SP. Reverse-phase HPLC of immunoreactive fractions resolved two immunoreactive peptides representing oxidised and reduced forms of a single peptide. 5. These data suggest that the nervous system of H. aspersa contains a single tachykinin with C-terminal structural characteristics similar to mammalian SP."} {"id": "PMID:1280546", "title": "Time course of glutamate receptor expression in individual oocytes of Xenopus laevis after injection of rat brain RNA.", "content": "1. The receptor for the neurotransmitter glutamate was functionally expressed in oocytes of Xenopus laevis after microinjection of rat brain RNA. The functional differentiation of this receptor type was further analyzed. 2. The development of the sensitivity to the agonists showed a time course which was differential for the various ligands in individual oocytes. 3. Sensitivity appeared after one day for kainate (KA), after two days for alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and quisqualate (QA), and after five days for N-methyl-D-aspartate (NMDA). 4. The KA response was markedly reduced by simultaneous application of AMPA. This was even found on the first day when an agonistic AMPA reaction was not detectable. 5. NMDA and non-NMDA receptors can clearly be differentiated by their delay of expression.", "contents": "Time course of glutamate receptor expression in individual oocytes of Xenopus laevis after injection of rat brain RNA. 1. The receptor for the neurotransmitter glutamate was functionally expressed in oocytes of Xenopus laevis after microinjection of rat brain RNA. The functional differentiation of this receptor type was further analyzed. 2. The development of the sensitivity to the agonists showed a time course which was differential for the various ligands in individual oocytes. 3. Sensitivity appeared after one day for kainate (KA), after two days for alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) and quisqualate (QA), and after five days for N-methyl-D-aspartate (NMDA). 4. The KA response was markedly reduced by simultaneous application of AMPA. This was even found on the first day when an agonistic AMPA reaction was not detectable. 5. NMDA and non-NMDA receptors can clearly be differentiated by their delay of expression."} {"id": "PMID:1280547", "title": "Second messengers and ion channels in acetylcholine-induced chloride secretion in hen trachea.", "content": "1. Hen tracheal epithelium can be stimulated by serosal application of acetylcholine (ACh) to secrete Cl- equal to approximately 60-90 microA/cm2. 2. Radio-ligand-displacement for IP3, cAMP and cGMP and ion channel selective drugs in voltage clamp set-ups were employed to characterize second messengers and Cl-, K+ and Ca2+ channels involved in the ACh response. 3. ACh induced a significant rise in IP3 in isolated tracheocytes, while ACh did not influence the production of cAMP in whole tissue, isolated tracheocytes or basolateral cell membrane vesicles. Further ACh desensitization did not effect cAMP level in tracheocytes. In addition neither ACh stimulation nor desensitization interfered with cAMP production in presence of 4.5 microM forskolin in tracheocytes, a level of forskolin rising base level cAMP by around five fold. 4. Around 35% of ACh Cl- secretion depends on Ca2+ mobilization from internal stores and about 65% on Ca2+ influx over basolateral membrane. The activated Ca2+ channel is insensitive to class I, II, III and IV Ca2+ antagonists. 5. A 23187 can mimic the ACh effect although 30% is indomethacin-sensitive demonstrating a prostaglandin activated adenylyl cyclase. 6. Two K+ channels are involved in ACh secretion, one sensitive to Ba2+ and quinine and both insensitive to 4-aminopyridine, apamin, charybdotoxin and TEA. 7. Flufenamate and triaminopyrimidine block a non-selective ion channel likely involved in the ACh response. An ACh activated apical Cl- channel is NPPB-sensitive.", "contents": "Second messengers and ion channels in acetylcholine-induced chloride secretion in hen trachea. 1. Hen tracheal epithelium can be stimulated by serosal application of acetylcholine (ACh) to secrete Cl- equal to approximately 60-90 microA/cm2. 2. Radio-ligand-displacement for IP3, cAMP and cGMP and ion channel selective drugs in voltage clamp set-ups were employed to characterize second messengers and Cl-, K+ and Ca2+ channels involved in the ACh response. 3. ACh induced a significant rise in IP3 in isolated tracheocytes, while ACh did not influence the production of cAMP in whole tissue, isolated tracheocytes or basolateral cell membrane vesicles. Further ACh desensitization did not effect cAMP level in tracheocytes. In addition neither ACh stimulation nor desensitization interfered with cAMP production in presence of 4.5 microM forskolin in tracheocytes, a level of forskolin rising base level cAMP by around five fold. 4. Around 35% of ACh Cl- secretion depends on Ca2+ mobilization from internal stores and about 65% on Ca2+ influx over basolateral membrane. The activated Ca2+ channel is insensitive to class I, II, III and IV Ca2+ antagonists. 5. A 23187 can mimic the ACh effect although 30% is indomethacin-sensitive demonstrating a prostaglandin activated adenylyl cyclase. 6. Two K+ channels are involved in ACh secretion, one sensitive to Ba2+ and quinine and both insensitive to 4-aminopyridine, apamin, charybdotoxin and TEA. 7. Flufenamate and triaminopyrimidine block a non-selective ion channel likely involved in the ACh response. An ACh activated apical Cl- channel is NPPB-sensitive."} {"id": "PMID:1280548", "title": "A short-term test for nucleotoxicity that uses chick embryo cells treated in vitro and in vivo--physico-chemical and biochemical investigations.", "content": "1. In vitro, some nucleotoxic or potentially nucleotoxic agents were tested with freshly isolated liver and brain cells from chick embryos as well as with thymic cells of the rat. 2. In vivo, chicken embryos were exposed to X-rays, methyl methanesulfonate, methyl nitrosourea, triethylene thiophosphoramide, and dimethylnitrosamine. 3. The toxic effects were determined by viscometry of alkaline cell lysates, nucleoid sedimentation, scheduled (SDS) and unscheduled (UDS) DNA synthesis and/or RNA synthesis. 4. The dose-effect curves obtained in vitro show that directly acting genotoxic agents are detected by the embryonic cells with equal or comparable sensitivity as by mammalian cells. 5. In vivo, genotoxicity is reflected by a decrease in alkaline lysate viscosity, nucleoid sedimentation and SDS and an increase in UDS. 6. From the present results it is suggested that chick embryo cells offer a simple, rapid and inexpensive short-term nucleotoxicity test for directly acting agents, the main disadvantage being the innate inability to biotransform indirectly acting agents.", "contents": "A short-term test for nucleotoxicity that uses chick embryo cells treated in vitro and in vivo--physico-chemical and biochemical investigations. 1. In vitro, some nucleotoxic or potentially nucleotoxic agents were tested with freshly isolated liver and brain cells from chick embryos as well as with thymic cells of the rat. 2. In vivo, chicken embryos were exposed to X-rays, methyl methanesulfonate, methyl nitrosourea, triethylene thiophosphoramide, and dimethylnitrosamine. 3. The toxic effects were determined by viscometry of alkaline cell lysates, nucleoid sedimentation, scheduled (SDS) and unscheduled (UDS) DNA synthesis and/or RNA synthesis. 4. The dose-effect curves obtained in vitro show that directly acting genotoxic agents are detected by the embryonic cells with equal or comparable sensitivity as by mammalian cells. 5. In vivo, genotoxicity is reflected by a decrease in alkaline lysate viscosity, nucleoid sedimentation and SDS and an increase in UDS. 6. From the present results it is suggested that chick embryo cells offer a simple, rapid and inexpensive short-term nucleotoxicity test for directly acting agents, the main disadvantage being the innate inability to biotransform indirectly acting agents."} {"id": "PMID:1280549", "title": "Systemic contact dermatitis from subcutaneous hydromorphone.", "content": "We report a patient who developed a generalized dermatitis after a period of progressive local intolerance to continuous subcutaneous infusion of hydromorphone for cancer pain. Sensitization to hydromorphone was proved by a positive patch test. Infusions with an equianalgesic dose of diacetylmorphine were well tolerated, without local or systemic side-effects, and prolonged the duration of infusion sites.", "contents": "Systemic contact dermatitis from subcutaneous hydromorphone. We report a patient who developed a generalized dermatitis after a period of progressive local intolerance to continuous subcutaneous infusion of hydromorphone for cancer pain. Sensitization to hydromorphone was proved by a positive patch test. Infusions with an equianalgesic dose of diacetylmorphine were well tolerated, without local or systemic side-effects, and prolonged the duration of infusion sites."} {"id": "PMID:1280550", "title": "Growth factor-dependent phosphorylation of membrane proteins in cultured human retinal pigment epithelial cells.", "content": "Recently, growth factors are known to phosphorylate tyrosine residues of proteins to regulate cellular functions. We investigated growth factor-dependent phosphorylation of membrane proteins in cultured human retinal pigment epithelial (RPE) cells. The phosphorylation experiments were done in membrane preparations of cultured RPE cell and the reaction was started by applying [32P]adenosine 5'-triphosphate (ATP) at 0 degrees C, and terminated after 0, 1, 5, 15, and 30 min. The samples were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and were analyzed by autoradiography. Many proteins showed time-dependent phosphorylation. Among them, a 170 kDa protein showed platelet-derived growth factor (PDGF)-specific phosphorylation with both time- (up to 30 min) and dose-(maximal effect at 50 ng/ml) dependence. On the other hand, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) showed no specific phosphorylation. Phosphoaminoacids of the 170 kDa protein were analyzed by thin layer chromatography and autoradiography. Phosphotyrosine showed much higher radioactivity than phosphoserine or phosphothreonine. Consequently, PDGF induced phosphorylation of the 170 kDa protein which mainly consisted of phosphotyrosine. The data suggest that tyrosine phosphorylation of membrane protein is involved in signal transduction of PDGF in human RPE cells.", "contents": "Growth factor-dependent phosphorylation of membrane proteins in cultured human retinal pigment epithelial cells. Recently, growth factors are known to phosphorylate tyrosine residues of proteins to regulate cellular functions. We investigated growth factor-dependent phosphorylation of membrane proteins in cultured human retinal pigment epithelial (RPE) cells. The phosphorylation experiments were done in membrane preparations of cultured RPE cell and the reaction was started by applying [32P]adenosine 5'-triphosphate (ATP) at 0 degrees C, and terminated after 0, 1, 5, 15, and 30 min. The samples were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and were analyzed by autoradiography. Many proteins showed time-dependent phosphorylation. Among them, a 170 kDa protein showed platelet-derived growth factor (PDGF)-specific phosphorylation with both time- (up to 30 min) and dose-(maximal effect at 50 ng/ml) dependence. On the other hand, epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) showed no specific phosphorylation. Phosphoaminoacids of the 170 kDa protein were analyzed by thin layer chromatography and autoradiography. Phosphotyrosine showed much higher radioactivity than phosphoserine or phosphothreonine. Consequently, PDGF induced phosphorylation of the 170 kDa protein which mainly consisted of phosphotyrosine. The data suggest that tyrosine phosphorylation of membrane protein is involved in signal transduction of PDGF in human RPE cells."} {"id": "PMID:1280551", "title": "Increased expression of keratin polypeptides in long term culture of adult rat hepatocytes.", "content": "Adult rat hepatocyte cultures showed the presence of albumin after 1 week of seeding. As the cultures aged, the cells commenced expressing alpha-foetoprotein and later keratin polypeptides 55 and 52 kD but ceased expressing albumin and alpha-foetoprotein. Enhanced expression of keratin polypeptides was confirmed by Western blot analysis in long term cultures. A possible mechanism for dedifferentiation of hepatocytes in culture is discussed.", "contents": "Increased expression of keratin polypeptides in long term culture of adult rat hepatocytes. Adult rat hepatocyte cultures showed the presence of albumin after 1 week of seeding. As the cultures aged, the cells commenced expressing alpha-foetoprotein and later keratin polypeptides 55 and 52 kD but ceased expressing albumin and alpha-foetoprotein. Enhanced expression of keratin polypeptides was confirmed by Western blot analysis in long term cultures. A possible mechanism for dedifferentiation of hepatocytes in culture is discussed."} {"id": "PMID:1280552", "title": "Thrombus imaging in dogs with a monoclonal antibody (SZ-51) specific for activated human platelets.", "content": "To specifically detect the localization of thrombus in vivo, we prepared a monoclonal antibody (McAb) SZ-51 specific for an alpha-granule membrane protein (GMP-140) on the surface of activated human platelets. The thrombus binding rate in vitro was 80 +/- 5% for 131I-SZ-51 and 4.4 +/- 0.5% for 131I-nonimmune IgG. Owing to the crossreaction of McAb SZ-51 with the activated platelets of dogs, thrombus in the femoral artery and vein of dogs was formed and imaged with single photon emission computerized tomography (SPECT). The ratio of thrombus to blood radioactivity (T/B) was 2.1, 4.8, 14.0 and 18.0 at 1, 2, 3 and 4 hours after injection of 131I-SZ-51 (0.6 mCi, 50 micrograms) into the arterial thrombus respectively, while the T/B ratio was 1.7, 2.2, 5.3 and 8.0 for venous one. The injection of 131I-nonimmune IgG at the same doses yielded a T/B ratio of 1.2 +/- 0.3 at each time period for both arterial and venous thrombi. These findings were in good agreement with the counting of removed thrombi 24 hours after the injection of radiotracer. The ratio was 21.7 and 2.6 for the 131I-SZ-51 in the arterial and venous thrombus, respectively. However, there were only 1.48 and 1.6 for the 131I-nonimmune IgG. These results indicate the great potentiality of McAb SZ-51 in application to detection of thrombi in vivo.", "contents": "Thrombus imaging in dogs with a monoclonal antibody (SZ-51) specific for activated human platelets. To specifically detect the localization of thrombus in vivo, we prepared a monoclonal antibody (McAb) SZ-51 specific for an alpha-granule membrane protein (GMP-140) on the surface of activated human platelets. The thrombus binding rate in vitro was 80 +/- 5% for 131I-SZ-51 and 4.4 +/- 0.5% for 131I-nonimmune IgG. Owing to the crossreaction of McAb SZ-51 with the activated platelets of dogs, thrombus in the femoral artery and vein of dogs was formed and imaged with single photon emission computerized tomography (SPECT). The ratio of thrombus to blood radioactivity (T/B) was 2.1, 4.8, 14.0 and 18.0 at 1, 2, 3 and 4 hours after injection of 131I-SZ-51 (0.6 mCi, 50 micrograms) into the arterial thrombus respectively, while the T/B ratio was 1.7, 2.2, 5.3 and 8.0 for venous one. The injection of 131I-nonimmune IgG at the same doses yielded a T/B ratio of 1.2 +/- 0.3 at each time period for both arterial and venous thrombi. These findings were in good agreement with the counting of removed thrombi 24 hours after the injection of radiotracer. The ratio was 21.7 and 2.6 for the 131I-SZ-51 in the arterial and venous thrombus, respectively. However, there were only 1.48 and 1.6 for the 131I-nonimmune IgG. These results indicate the great potentiality of McAb SZ-51 in application to detection of thrombi in vivo."} {"id": "PMID:1280553", "title": "Photo-bleaching and photon saturation in flow cytometry.", "content": "In flow cytometry, small particles travel at a high speed through a bright light spot. The high light intensity at the point of measurement causes measurable photon saturation. This observation indicates that the rate at which individual dye molecules emit photons is close to the maximum emission rate. Despite the short exposure time, individual molecules may go through a few hundred excitation cycles while they are in the light beam. The absorbed light dose causes significant dye destruction. This article presents experimental procedures to determine the extent of photon saturation and photo-bleaching of dyes bound to cell nuclei in a flow cytometer. Measurements of Hoechst and propidium iodide bound to chromatin show that the amount of dye bleached per emitted photon is the same at low and high illumination intensities. This finding indicates that photon emission and dye destruction are both the result of the absorption of single excitation photons. The experimental observations allow rough estimates of the lifetime of the excited state and the lifetime of the molecule. The lifetime of the Hoechst 33258 bound to DNA is estimated to be 100 excitation-relaxation cycles. The average propidium iodide molecule lasts approximately 200 excitation-relaxation cycles. The theoretical considerations show that the optimal illumination conditions are different for bleaching and nonbleaching dyes. An optical arrangement for high precision measurements of bleaching dyes is presented.", "contents": "Photo-bleaching and photon saturation in flow cytometry. In flow cytometry, small particles travel at a high speed through a bright light spot. The high light intensity at the point of measurement causes measurable photon saturation. This observation indicates that the rate at which individual dye molecules emit photons is close to the maximum emission rate. Despite the short exposure time, individual molecules may go through a few hundred excitation cycles while they are in the light beam. The absorbed light dose causes significant dye destruction. This article presents experimental procedures to determine the extent of photon saturation and photo-bleaching of dyes bound to cell nuclei in a flow cytometer. Measurements of Hoechst and propidium iodide bound to chromatin show that the amount of dye bleached per emitted photon is the same at low and high illumination intensities. This finding indicates that photon emission and dye destruction are both the result of the absorption of single excitation photons. The experimental observations allow rough estimates of the lifetime of the excited state and the lifetime of the molecule. The lifetime of the Hoechst 33258 bound to DNA is estimated to be 100 excitation-relaxation cycles. The average propidium iodide molecule lasts approximately 200 excitation-relaxation cycles. The theoretical considerations show that the optimal illumination conditions are different for bleaching and nonbleaching dyes. An optical arrangement for high precision measurements of bleaching dyes is presented."} {"id": "PMID:1280554", "title": "Cell cycle analysis of asynchronous cell populations by flow cytometry using bromodeoxyuridine label and Hoechst-propidium iodide stain.", "content": "Continuous labelling of cells with deoxybromouridine (BrdUrd) followed by staining with a bis-benzimidazole (Hoechst 33258) and a phenanthridinium (propidium iodide or ethidium bromide) allows the cells to be separated by flow cytometry according to the extent of their DNA replication. This BrdUrd-Hoechst/PI method has been used mainly to observe perturbations of the cell cycle in synchronously growing cells. In this paper we demonstrate that, when the method is applied to asynchronously dividing cells, more extensive information can be derived about the effects of cytotoxic and other treatments on the kinetics of the cell cycle. The interpretation of the data is explained, the effects of different types of cytotoxic agent are described, and the method is compared briefly to other methods for following cell cycle kinetics.", "contents": "Cell cycle analysis of asynchronous cell populations by flow cytometry using bromodeoxyuridine label and Hoechst-propidium iodide stain. Continuous labelling of cells with deoxybromouridine (BrdUrd) followed by staining with a bis-benzimidazole (Hoechst 33258) and a phenanthridinium (propidium iodide or ethidium bromide) allows the cells to be separated by flow cytometry according to the extent of their DNA replication. This BrdUrd-Hoechst/PI method has been used mainly to observe perturbations of the cell cycle in synchronously growing cells. In this paper we demonstrate that, when the method is applied to asynchronously dividing cells, more extensive information can be derived about the effects of cytotoxic and other treatments on the kinetics of the cell cycle. The interpretation of the data is explained, the effects of different types of cytotoxic agent are described, and the method is compared briefly to other methods for following cell cycle kinetics."} {"id": "PMID:1280555", "title": "Streptavidin-based quantitative staining of intracellular antigens for flow cytometric analysis.", "content": "A streptavidin-biotin-based three-step immunolabeling protocol for quantitative staining of intracellular antigens for flow cytometric analysis was evaluated using simian virus 40 (SV40) large T antigen. The concentration as well as the quantity of antibody used required optimization. The optimum labeling conditions varied moderately with cell lines that express T antigen levels over a 40-50-fold range. The procedure resulted in specific fluorescence 2.4 times higher than that using a comparable two-step indirect immunofluorescence technique. The gain in resolution was shown to be greater when staining cells with lower antigen levels. In the analysis of background fluorescence, the principal components were, as for the two-step technique, autofluorescence and propidium spectral overlap. While streptavidin does add to the background, the increase is relatively small. Decreasing the propidium concentration from 50 micrograms/ml to 5 micrograms/ml was found to reduce significantly the level of background from this source. Theoretical aspects of quantitative staining and of resolution versus quantification are discussed.", "contents": "Streptavidin-based quantitative staining of intracellular antigens for flow cytometric analysis. A streptavidin-biotin-based three-step immunolabeling protocol for quantitative staining of intracellular antigens for flow cytometric analysis was evaluated using simian virus 40 (SV40) large T antigen. The concentration as well as the quantity of antibody used required optimization. The optimum labeling conditions varied moderately with cell lines that express T antigen levels over a 40-50-fold range. The procedure resulted in specific fluorescence 2.4 times higher than that using a comparable two-step indirect immunofluorescence technique. The gain in resolution was shown to be greater when staining cells with lower antigen levels. In the analysis of background fluorescence, the principal components were, as for the two-step technique, autofluorescence and propidium spectral overlap. While streptavidin does add to the background, the increase is relatively small. Decreasing the propidium concentration from 50 micrograms/ml to 5 micrograms/ml was found to reduce significantly the level of background from this source. Theoretical aspects of quantitative staining and of resolution versus quantification are discussed."} {"id": "PMID:1280556", "title": "Improved BrdUrd-Hoechst bivariate cell kinetic analysis by helium-cadmium single laser excitation.", "content": "In laser based flow cytometers, UV excitation of Hoechst 33258 and propidium iodide (PI) or ethidium bromide (EB) is performed with 351/364 nm high power lines of UV-capable argon ion lasers, which are expensive and short-lived. In this paper we note for the first time that helium-cadmium lasers emitting 10 to 30 mW at 325 nm are even more superior for cell kinetic bivariate bromodeoxyuridine (BrdUrd)/Hoechst PI or EB cell cycle analysis. HeCd single laser UV excitation gives comparable CVs for cell cycle distributions, and almost normal G2M/G1 ratios of 1.9 to 2.0 for all cell cycles. This is shown for synchronous and asynchronous cell populations on a FACStar+ and an Ortho Cytofluorograf. Therefore we recommend helium-cadmium lasers as low-power, cheap, and long-lived UV excitation sources for the cytochemically simple but high resolution multiparameter BrdUrd-Hoechst cell kinetic analysis.", "contents": "Improved BrdUrd-Hoechst bivariate cell kinetic analysis by helium-cadmium single laser excitation. In laser based flow cytometers, UV excitation of Hoechst 33258 and propidium iodide (PI) or ethidium bromide (EB) is performed with 351/364 nm high power lines of UV-capable argon ion lasers, which are expensive and short-lived. In this paper we note for the first time that helium-cadmium lasers emitting 10 to 30 mW at 325 nm are even more superior for cell kinetic bivariate bromodeoxyuridine (BrdUrd)/Hoechst PI or EB cell cycle analysis. HeCd single laser UV excitation gives comparable CVs for cell cycle distributions, and almost normal G2M/G1 ratios of 1.9 to 2.0 for all cell cycles. This is shown for synchronous and asynchronous cell populations on a FACStar+ and an Ortho Cytofluorograf. Therefore we recommend helium-cadmium lasers as low-power, cheap, and long-lived UV excitation sources for the cytochemically simple but high resolution multiparameter BrdUrd-Hoechst cell kinetic analysis."} {"id": "PMID:1280557", "title": "Perturbation of developmental gene expression in rat liver by fibric acid derivatives: lipoprotein lipase and alpha-fetoprotein as models.", "content": "Liver lipoprotein lipase (LPL) and alpha-fetoprotein (AFP) gene expression show similar developmental patterns. Both mRNAs are abundantly expressed in neonatal rat liver and gradually disappear upon ageing. Treatment with fibric acid derivatives, such as fenofibrate, not only delays the developmental extinction of the LPL gene, but also increases LPL mRNA levels in neonatal rat liver. Similarly, the developmental extinction of the AFP gene in the liver is clearly delayed after fenofibrate. In adult rat liver, fibric acid derivatives transcriptionally reinduce a mRNA with similar size as LPL, but no effect on AFP mRNA was detected. Sequence comparison of clones isolated from a fenofibrate-induced cDNA library demonstrates that the fenofibrate-(re)induced mRNA in adult rat liver is encoding for LPL. The induction of LPL after fenofibrate is tissue-specific, since heart and adipose tissue LPL mRNA levels remain unchanged. In conclusion, fibric acid derivatives modulate developmental expression patterns in rat liver, and may selectively reinduce the expression of extinct genes in adult rat liver.", "contents": "Perturbation of developmental gene expression in rat liver by fibric acid derivatives: lipoprotein lipase and alpha-fetoprotein as models. Liver lipoprotein lipase (LPL) and alpha-fetoprotein (AFP) gene expression show similar developmental patterns. Both mRNAs are abundantly expressed in neonatal rat liver and gradually disappear upon ageing. Treatment with fibric acid derivatives, such as fenofibrate, not only delays the developmental extinction of the LPL gene, but also increases LPL mRNA levels in neonatal rat liver. Similarly, the developmental extinction of the AFP gene in the liver is clearly delayed after fenofibrate. In adult rat liver, fibric acid derivatives transcriptionally reinduce a mRNA with similar size as LPL, but no effect on AFP mRNA was detected. Sequence comparison of clones isolated from a fenofibrate-induced cDNA library demonstrates that the fenofibrate-(re)induced mRNA in adult rat liver is encoding for LPL. The induction of LPL after fenofibrate is tissue-specific, since heart and adipose tissue LPL mRNA levels remain unchanged. In conclusion, fibric acid derivatives modulate developmental expression patterns in rat liver, and may selectively reinduce the expression of extinct genes in adult rat liver."} {"id": "PMID:1280558", "title": "TRP-2/DT, a new early melanoblast marker, shows that steel growth factor (c-kit ligand) is a survival factor.", "content": "We have used a probe derived from TRP-2/DT to detect migratory melanoblasts shortly after they emerge from the neural crest, as early as 10 days post coitum (dpc). TRP-2/DT expression is otherwise restricted to the presumptive pigmented retinal epithelium, the developing telencephalon and the endolymphatic duct. The pattern of steel and c-kit hybridisation in the developing brain differed from that of TRP-2. TRP-1 and tyrosinase probes also detected melanoblasts but were both expressed later in development than TRP-2. We used the TRP-2/DT probe to investigate the way that the Steel-dickie (Sld) mutation interferes with melanocyte development, and found that the membrane-bound steel growth factor which is missing in Sld/Sld mutants is necessary for the survival of melanoblasts but not for their early migration and initial differentiation.", "contents": "TRP-2/DT, a new early melanoblast marker, shows that steel growth factor (c-kit ligand) is a survival factor. We have used a probe derived from TRP-2/DT to detect migratory melanoblasts shortly after they emerge from the neural crest, as early as 10 days post coitum (dpc). TRP-2/DT expression is otherwise restricted to the presumptive pigmented retinal epithelium, the developing telencephalon and the endolymphatic duct. The pattern of steel and c-kit hybridisation in the developing brain differed from that of TRP-2. TRP-1 and tyrosinase probes also detected melanoblasts but were both expressed later in development than TRP-2. We used the TRP-2/DT probe to investigate the way that the Steel-dickie (Sld) mutation interferes with melanocyte development, and found that the membrane-bound steel growth factor which is missing in Sld/Sld mutants is necessary for the survival of melanoblasts but not for their early migration and initial differentiation."} {"id": "PMID:1280559", "title": "Developmentally regulated cell surface expression and function of c-kit receptor during lymphocyte ontogeny in the embryo and adult mice.", "content": "We have used a c-kit-specific monoclonal antibody, immuno-fluorescence staining and flow fluorocytometry or microscopy analysis to assess the cell surface expression of the c-kit receptor on a panel of non-transformed clones representing different stages of T- and B-lymphocyte development, freshly isolated lymphoid cells from thymus, bone marrow and spleen of young adult C57BL/6 mice and cells from yolk sac, thymus and liver of developing C57BL/6 mouse embryos. Pro-T, Pro-B and Pre-B clones derived from thymus or liver of 14-day embryos are c-kit+. Starting at day 8 to 8.5 in yolk sac, day-10 in fetal liver, and day 11 to 12 in fetal thymus, there are many c-kit+ cells. The number of c-kit+ cells in liver and thymus increases up to day 15 and progressively decreases thereafter. Cell sorter purified c-kit+ day 14 fetal liver cells fully reconstitute the T and B cell compartments of immunodeficient Scid mice. Stromal cells or epithelial cells derived from fetal thymus or liver, which can support growth and differentiation of c-kit+ lymphocyte progenitor clones, synthesize mRNA for Steel Factor (SF), the ligand of c-kit. In the adult mouse, however, c-kit expression is restricted to very early stages of T- and B-lymphocyte development (multipotent progenitors, B-cell/myelocytic progenitors, Pro-T and Pro-B lymphocyte progenitors). Most cells at the Pre-T, Pre-B and later stages of development do not bear detectable c-kit. Using Cos-1 cells transfected with mouse SF-cDNA and an antagonistic c-kit receptor-specific antibody, we show that the c-kit/SF system contributes to the survival of lymphocyte progenitors and enhances the proliferative responses of these cells to other growth factors (i.e. IL2, IL3, IL4, IL7). However, the c-kit receptor/SF ligand pair is neither sufficient nor necessary for the differentiation of lymphocyte progenitors into mature T- or B-lymphocytes. Finally, in stromal cell lines from fetal liver and adult bone marrow and thymic epithelial cell lines the level of steady state SF-RNA transcripts is inversely correlated with that of IL-7-mRNA. Moreover, IL7 inhibits the synthesis of SF-mRNA in stromal cells and rIL6 abrogates this inhibitory effect of rIL7. Thus, the expression of SF in stromal cells is subjected to complex regulation by other cytokines produced by the same stromal cells or by neighboring cells in a given microenvironment.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Developmentally regulated cell surface expression and function of c-kit receptor during lymphocyte ontogeny in the embryo and adult mice. We have used a c-kit-specific monoclonal antibody, immuno-fluorescence staining and flow fluorocytometry or microscopy analysis to assess the cell surface expression of the c-kit receptor on a panel of non-transformed clones representing different stages of T- and B-lymphocyte development, freshly isolated lymphoid cells from thymus, bone marrow and spleen of young adult C57BL/6 mice and cells from yolk sac, thymus and liver of developing C57BL/6 mouse embryos. Pro-T, Pro-B and Pre-B clones derived from thymus or liver of 14-day embryos are c-kit+. Starting at day 8 to 8.5 in yolk sac, day-10 in fetal liver, and day 11 to 12 in fetal thymus, there are many c-kit+ cells. The number of c-kit+ cells in liver and thymus increases up to day 15 and progressively decreases thereafter. Cell sorter purified c-kit+ day 14 fetal liver cells fully reconstitute the T and B cell compartments of immunodeficient Scid mice. Stromal cells or epithelial cells derived from fetal thymus or liver, which can support growth and differentiation of c-kit+ lymphocyte progenitor clones, synthesize mRNA for Steel Factor (SF), the ligand of c-kit. In the adult mouse, however, c-kit expression is restricted to very early stages of T- and B-lymphocyte development (multipotent progenitors, B-cell/myelocytic progenitors, Pro-T and Pro-B lymphocyte progenitors). Most cells at the Pre-T, Pre-B and later stages of development do not bear detectable c-kit. Using Cos-1 cells transfected with mouse SF-cDNA and an antagonistic c-kit receptor-specific antibody, we show that the c-kit/SF system contributes to the survival of lymphocyte progenitors and enhances the proliferative responses of these cells to other growth factors (i.e. IL2, IL3, IL4, IL7). However, the c-kit receptor/SF ligand pair is neither sufficient nor necessary for the differentiation of lymphocyte progenitors into mature T- or B-lymphocytes. Finally, in stromal cell lines from fetal liver and adult bone marrow and thymic epithelial cell lines the level of steady state SF-RNA transcripts is inversely correlated with that of IL-7-mRNA. Moreover, IL7 inhibits the synthesis of SF-mRNA in stromal cells and rIL6 abrogates this inhibitory effect of rIL7. Thus, the expression of SF in stromal cells is subjected to complex regulation by other cytokines produced by the same stromal cells or by neighboring cells in a given microenvironment.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1280560", "title": "Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila.", "content": "hedgehog is a segment polarity gene necessary to maintain the proper organization of each segment of the Drosophila embryo. We have identified the physical location of a number of rearrangement breakpoints associated with hedgehog mutations. The corresponding hh RNA is expressed in a series of segmental stripes starting at cellular blastoderm in the posterior portion of each segment. This RNA is localized predominantly within nuclei until stage 10, when the localization becomes primarily cytoplasmic. Expression of hh RNA in the posterior compartment is independent of most other segment polarity genes, including en, until the late extended germ-band stage (stage 11). Sequence analysis of the hedgehog locus suggests the protein product is a transmembrane protein, which may, therefore, be directly involved in cell-cell communication.", "contents": "Molecular organization and embryonic expression of the hedgehog gene involved in cell-cell communication in segmental patterning of Drosophila. hedgehog is a segment polarity gene necessary to maintain the proper organization of each segment of the Drosophila embryo. We have identified the physical location of a number of rearrangement breakpoints associated with hedgehog mutations. The corresponding hh RNA is expressed in a series of segmental stripes starting at cellular blastoderm in the posterior portion of each segment. This RNA is localized predominantly within nuclei until stage 10, when the localization becomes primarily cytoplasmic. Expression of hh RNA in the posterior compartment is independent of most other segment polarity genes, including en, until the late extended germ-band stage (stage 11). Sequence analysis of the hedgehog locus suggests the protein product is a transmembrane protein, which may, therefore, be directly involved in cell-cell communication."} {"id": "PMID:1280562", "title": "Prediction of response to drug therapy of cancer. A review of in vitro assays.", "content": "Cancer chemotherapy has witnessed a great deal of progress since the introduction of the nitrogen mustards in the 1940s. Unfortunately, individual patients with apparently identical tumour histologies do not always respond identically to the same drug regimen. Determining the sensitivity and resistance of an organism before treatment has been the standard of care in infectious diseases for many years, while in oncology treatment has been initiated according to tumour histology rather than the tumour's sensitivity to a given agent. Attempts to individualise therapy have been the goal of oncologists since the 1950s. Since that time a number of in vitro assays have been developed to predict therapeutic outcome prior to the start of therapy. In the 1970s, with the introduction of the human tumour stem cell assay, it was generally believed that oncology was on the threshold of entering an era of predictive in vitro chemosensitivity testing. Unfortunately, this assay was shown to have a number of technical drawbacks including the low plating efficiencies of many primary tumour samples which thus limits the percentage which can be evaluated, leaving us still at this threshold today. Several recent developments, such as the Kern assay, which measures inhibition of radioactive precursors into tumour cells in the presence of antineoplastic agents, ATP bioluminescence assays, and the fluorescent cytoprint assay offer the promise of rapid and sensitive results. Other assays, such as the tetrazolium-based MTT and the sulphorhodamine blue assay appear to hold more promise in the screening and evaluation of potential new agents in established tumour cell lines than for evaluating chemosensitivity of clinical specimens. However, before a particular assay can be considered as an in vitro test of chemosensitivity or resistance, controlled prospective studies must be carried out to validate the assay in a number of different tumour types.", "contents": "Prediction of response to drug therapy of cancer. A review of in vitro assays. Cancer chemotherapy has witnessed a great deal of progress since the introduction of the nitrogen mustards in the 1940s. Unfortunately, individual patients with apparently identical tumour histologies do not always respond identically to the same drug regimen. Determining the sensitivity and resistance of an organism before treatment has been the standard of care in infectious diseases for many years, while in oncology treatment has been initiated according to tumour histology rather than the tumour's sensitivity to a given agent. Attempts to individualise therapy have been the goal of oncologists since the 1950s. Since that time a number of in vitro assays have been developed to predict therapeutic outcome prior to the start of therapy. In the 1970s, with the introduction of the human tumour stem cell assay, it was generally believed that oncology was on the threshold of entering an era of predictive in vitro chemosensitivity testing. Unfortunately, this assay was shown to have a number of technical drawbacks including the low plating efficiencies of many primary tumour samples which thus limits the percentage which can be evaluated, leaving us still at this threshold today. Several recent developments, such as the Kern assay, which measures inhibition of radioactive precursors into tumour cells in the presence of antineoplastic agents, ATP bioluminescence assays, and the fluorescent cytoprint assay offer the promise of rapid and sensitive results. Other assays, such as the tetrazolium-based MTT and the sulphorhodamine blue assay appear to hold more promise in the screening and evaluation of potential new agents in established tumour cell lines than for evaluating chemosensitivity of clinical specimens. However, before a particular assay can be considered as an in vitro test of chemosensitivity or resistance, controlled prospective studies must be carried out to validate the assay in a number of different tumour types."} {"id": "PMID:1280563", "title": "Histamine H2-receptor antagonists in peptic ulcer disease. Efficacy in healing peptic ulcers.", "content": "Duodenal ulcer healing depends on the degree and length of inhibition of gastric secretion and upon the duration of therapy, while gastric ulcer healing is dependent mainly on the duration of therapy. Currently marketed doses of the histamine H2-receptor antagonists heal between 77 and 92% of duodenal ulcers at 4 weeks, and adjuvant treatment to eradicate Helicobacter pylori increases this rate. Once-daily administration is as effective as more frequent dosing regimens and may even result in higher healing rates. Gastric ulcers heal more slowly, but 75 to 88% of ulcers heal after 8 weeks of treatment. While newer more potent acid suppressors such as omeprazole heal ulcers slightly more quickly, the H2-receptor antagonists have an unparalleled safety record of over 15 years. It is unlikely that the prostaglandin analogues can improve on the efficacy of the H2-receptor antagonists with as low an incidence of side effects.", "contents": "Histamine H2-receptor antagonists in peptic ulcer disease. Efficacy in healing peptic ulcers. Duodenal ulcer healing depends on the degree and length of inhibition of gastric secretion and upon the duration of therapy, while gastric ulcer healing is dependent mainly on the duration of therapy. Currently marketed doses of the histamine H2-receptor antagonists heal between 77 and 92% of duodenal ulcers at 4 weeks, and adjuvant treatment to eradicate Helicobacter pylori increases this rate. Once-daily administration is as effective as more frequent dosing regimens and may even result in higher healing rates. Gastric ulcers heal more slowly, but 75 to 88% of ulcers heal after 8 weeks of treatment. While newer more potent acid suppressors such as omeprazole heal ulcers slightly more quickly, the H2-receptor antagonists have an unparalleled safety record of over 15 years. It is unlikely that the prostaglandin analogues can improve on the efficacy of the H2-receptor antagonists with as low an incidence of side effects."} {"id": "PMID:1280564", "title": "Use of plasma volume expanders in myocardial revascularisation.", "content": "The optimal solution for priming cardiopulmonary bypass machines and for postoperative resuscitation following myocardial revascularisation should be inexpensive, free of risk of transmitting disease, and free of other detrimental side effects. Colloid solutions are preferred over crystalloid solutions because of elevations in extracellular sodium and water that occur with cardiopulmonary bypass. Albumin, plasma protein solution, hetastarch (hydroxyethyl starch) and dextran are available for use if blood is not necessary and mediastinal blood is not available. Hetastarch is associated with a lower risk of bleeding and less risk of allergic reaction than dextran, and its cost is substantially less than that of albumin. However, high doses increase the risk of bleeding complications.", "contents": "Use of plasma volume expanders in myocardial revascularisation. The optimal solution for priming cardiopulmonary bypass machines and for postoperative resuscitation following myocardial revascularisation should be inexpensive, free of risk of transmitting disease, and free of other detrimental side effects. Colloid solutions are preferred over crystalloid solutions because of elevations in extracellular sodium and water that occur with cardiopulmonary bypass. Albumin, plasma protein solution, hetastarch (hydroxyethyl starch) and dextran are available for use if blood is not necessary and mediastinal blood is not available. Hetastarch is associated with a lower risk of bleeding and less risk of allergic reaction than dextran, and its cost is substantially less than that of albumin. However, high doses increase the risk of bleeding complications."} {"id": "PMID:1280565", "title": "Sinus node disease. Current concepts in diagnosis and therapy.", "content": "Sinus node disease (SND) encompasses a number of abnormalities of sinus impulse generation and transmission within the atria and may lead to both bradyarrhythmias and tachycardias. Such abnormalities may be due to primary atrial electrophysiological abnormalities, or be secondary to drugs or abnormal autonomic control. The diagnosis may be readily established from the surface ECG or Holter recordings in many cases, but invasive electrophysiological study or assessment of the effects of autonomic blockade may be required in symptomatic patients in whom the diagnosis is suspected but not confirmed by simple electrocardiographic monitoring. Treatment should be restricted to those patients in whom clear correlation between symptoms and electrocardiographic or electrophysiological abnormalities has been established. Although a number of pharmacological agents have been assessed, the treatment of bradyarrhythmias should be permanent pacing. There is now substantial evidence that physiological (atrial or dual chamber) pacing reduces atrial arrhythmias, systemic embolisation, progression to heart failure and mortality, compared to single chamber ventricular pacing. Antiarrhythmic therapy may be required to control atrial tachyarrhythmias if they persist following pacing. In patients with uncontrolled atrial arrhythmias, especially those with ventricular pacemakers, long term oral anticoagulation should be considered to reduce the risk of systemic embolisation which is a common complication in patients with the bradycardia/tachycardia syndrome.", "contents": "Sinus node disease. Current concepts in diagnosis and therapy. Sinus node disease (SND) encompasses a number of abnormalities of sinus impulse generation and transmission within the atria and may lead to both bradyarrhythmias and tachycardias. Such abnormalities may be due to primary atrial electrophysiological abnormalities, or be secondary to drugs or abnormal autonomic control. The diagnosis may be readily established from the surface ECG or Holter recordings in many cases, but invasive electrophysiological study or assessment of the effects of autonomic blockade may be required in symptomatic patients in whom the diagnosis is suspected but not confirmed by simple electrocardiographic monitoring. Treatment should be restricted to those patients in whom clear correlation between symptoms and electrocardiographic or electrophysiological abnormalities has been established. Although a number of pharmacological agents have been assessed, the treatment of bradyarrhythmias should be permanent pacing. There is now substantial evidence that physiological (atrial or dual chamber) pacing reduces atrial arrhythmias, systemic embolisation, progression to heart failure and mortality, compared to single chamber ventricular pacing. Antiarrhythmic therapy may be required to control atrial tachyarrhythmias if they persist following pacing. In patients with uncontrolled atrial arrhythmias, especially those with ventricular pacemakers, long term oral anticoagulation should be considered to reduce the risk of systemic embolisation which is a common complication in patients with the bradycardia/tachycardia syndrome."} {"id": "PMID:1280566", "title": "Heparin therapy. Regimens and treatment considerations.", "content": "Heparin is a parenteral antithrombotic agent with efficacy in the treatment and prevention of venous thromboembolic disease and in preinfarctional angina. Accumulating evidence also suggests that heparin is useful in the prevention of coronary artery reocclusion after thrombolytic therapy for acute myocardial infarction, and in the prevention of left ventricular mural thrombosis after anterior wall myocardial infarction. Heparin appears to offer only marginal benefit in reducing mortality when given in combination with thrombolytic therapy and aspirin for acute myocardial infarction. When used for prevention of venous thromboembolism in moderate risk patients, heparin should be given subcutaneously in a dose of 5000 U every 12 hours for 5 to 7 days or until the patient is ambulatory. In higher risk patients, such as those undergoing total hip replacement, heparin should be given subcutaneously every 12 hours in a dose to prolong the activated partial thromboplastin time (aPTT) by 4 to 5 seconds into the upper normal range. When used to treat active venous thromboembolism or the peri-infarctional state, heparin should be given by intravenous infusion with loading and maintenance doses to consistently prolong the aPTT to between 1.5- and 2.5-fold the control value (mean of laboratory's normal range). If constant intravenous infusion is not possible, the drug should be given subcutaneously every 12 hours to consistently prolong the aPTT between 1.5 and 2.5 times control. This regimen is also recommended in pregnant women with venous thromboembolic disease or mechanical heart valves.", "contents": "Heparin therapy. Regimens and treatment considerations. Heparin is a parenteral antithrombotic agent with efficacy in the treatment and prevention of venous thromboembolic disease and in preinfarctional angina. Accumulating evidence also suggests that heparin is useful in the prevention of coronary artery reocclusion after thrombolytic therapy for acute myocardial infarction, and in the prevention of left ventricular mural thrombosis after anterior wall myocardial infarction. Heparin appears to offer only marginal benefit in reducing mortality when given in combination with thrombolytic therapy and aspirin for acute myocardial infarction. When used for prevention of venous thromboembolism in moderate risk patients, heparin should be given subcutaneously in a dose of 5000 U every 12 hours for 5 to 7 days or until the patient is ambulatory. In higher risk patients, such as those undergoing total hip replacement, heparin should be given subcutaneously every 12 hours in a dose to prolong the activated partial thromboplastin time (aPTT) by 4 to 5 seconds into the upper normal range. When used to treat active venous thromboembolism or the peri-infarctional state, heparin should be given by intravenous infusion with loading and maintenance doses to consistently prolong the aPTT to between 1.5- and 2.5-fold the control value (mean of laboratory's normal range). If constant intravenous infusion is not possible, the drug should be given subcutaneously every 12 hours to consistently prolong the aPTT between 1.5 and 2.5 times control. This regimen is also recommended in pregnant women with venous thromboembolic disease or mechanical heart valves."} {"id": "PMID:1280567", "title": "Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy.", "content": "Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum and in the treatment of early Lyme disease. Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the above infections. Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to therapy with azithromycin (as is the case with erythromycin) indicating the need for physician vigilance, although it should be noted that azithromycin is of equivalent efficacy to amoxicillin in the treatment of such patients. In the therapy of urethritis/cervicitis associated with C. trachomatis, N. gonorrhoea or U. urealyticum, a single dose azithromycin regimen offers a distinct advantage over currently available pharmacological options, while providing effective therapy.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Azithromycin. A review of its antimicrobial activity, pharmacokinetic properties and clinical efficacy. Azithromycin is an acid stable orally administered macrolide antimicrobial drug, structurally related to erythromycin, with a similar spectrum of antimicrobial activity. Azithromycin is marginally less active than erythromycin in vitro against Gram-positive organisms, although this is of doubtful clinical significance as susceptibility concentrations fall within the range of achievable tissue azithromycin concentrations. In contrast, azithromycin appears to be more active than erythromycin against many Gram-negative pathogens and several other pathogens, notably Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Urea-plasma urealyticum and Borrelia burgdorferi. Like erythromycin and other macrolides, the activity of azithromycin is unaffected by the production of beta-lactamase. However, erythromycin-resistant organisms are also resistant to azithromycin. Following oral administration, serum concentrations of azithromycin are lower than those of erythromycin, but this reflects the rapid and extensive movement of the drug from the circulation into intracellular compartments resulting in tissue concentrations exceeding those commonly seen with erythromycin. Azithromycin is subsequently slowly released, reflecting its long terminal phase elimination half-life relative to that of erythromycin. These factors allow for a single dose or single daily dose regimen in most infections, with the potential for increased compliance among outpatients where a more frequent antimicrobial regimen might traditionally be indicated. The potential disadvantage of low azithromycin serum concentrations, however, is that breakthrough bacteraemia may occur in patients who are severely ill; nevertheless, animal studies suggest that tissue concentrations of azithromycin are more important than those in serum when treating respiratory and other infections. The clinical efficacy of azithromycin has been confirmed in the treatment of infections of the lower and upper respiratory tracts (the latter including paediatric patients), skin and soft tissues (again including paediatric patients), in uncomplicated urethritis/cervicitis associated with N. gonorrhoeae, Chlamydia trachomatis or U. urealyticum and in the treatment of early Lyme disease. Azithromycin was as effective as erythromycin and other commonly used drugs including clarithromycin, beta-lactams (penicillins and cephalosporins), and quinolone and tetracycline antibiotics in some of the above infections. Some patients with acute exacerbations of chronic bronchitis due to H. influenzae may be refractory to therapy with azithromycin (as is the case with erythromycin) indicating the need for physician vigilance, although it should be noted that azithromycin is of equivalent efficacy to amoxicillin in the treatment of such patients. In the therapy of urethritis/cervicitis associated with C. trachomatis, N. gonorrhoea or U. urealyticum, a single dose azithromycin regimen offers a distinct advantage over currently available pharmacological options, while providing effective therapy.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1280568", "title": "Cefodizime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.", "content": "Cefodizime is a third generation cephalosporin with a broad spectrum of antibacterial activity. Administered intravenously or intramuscularly, cefodizime 1 to 4 g daily for an average of 7 to 10 days produced clinical cure in 80 to 100% of patients (adults, elderly or children) with upper or lower respiratory tract infections or urinary tract infections, and in comparative trials cefodizime was as effective as other third generation cephalosporins. A single dose of cefodizime 1 or 2 g is also useful in treating lower urinary tract infections, particularly uncomplicated infections, with a rate of clinical success of 72 to 88%. Urogenital gonorrhoea, whether caused by beta-lactamase producing or non-beta-lactamase producing Neisseria gonorrhoeae, is very effectively treated by single dose therapy with intramuscular cefodizime 0.25 to 1 g (virtually 100% cured). Preliminary data from a small number of patients indicate that cefodizime may also be useful in the treatment of otitis media, sinusitis and gynaecological infections, and for the prophylaxis or treatment of surgical infections. The clinical efficacy of cefodizime in comparison with other third generation cephalosporins is superior to that predicted from in vitro results. This superior activity of cefodizime may be related to the relatively long elimination half-life of the drug or its ability to modify some functions of the immune system--a potentially important finding awaiting further investigation. Cefodizime is well tolerated and has a tolerability profile similar to other members of its class with systemic adverse events being primarily gastrointestinal or dermatological. Thus, limited comparative studies indicate cefodizime has the potential to become a useful alternative to current antimicrobial therapy for the treatment of a variety of infections. Cefodizime may be more convenient to administer than some other agents of its class as it may be given once or twice daily. While there are no trials comparing cefodizime to other third generation cephalosporins in immunosuppressed populations, preliminary information indicates cefodizime may be useful in this group.", "contents": "Cefodizime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Cefodizime is a third generation cephalosporin with a broad spectrum of antibacterial activity. Administered intravenously or intramuscularly, cefodizime 1 to 4 g daily for an average of 7 to 10 days produced clinical cure in 80 to 100% of patients (adults, elderly or children) with upper or lower respiratory tract infections or urinary tract infections, and in comparative trials cefodizime was as effective as other third generation cephalosporins. A single dose of cefodizime 1 or 2 g is also useful in treating lower urinary tract infections, particularly uncomplicated infections, with a rate of clinical success of 72 to 88%. Urogenital gonorrhoea, whether caused by beta-lactamase producing or non-beta-lactamase producing Neisseria gonorrhoeae, is very effectively treated by single dose therapy with intramuscular cefodizime 0.25 to 1 g (virtually 100% cured). Preliminary data from a small number of patients indicate that cefodizime may also be useful in the treatment of otitis media, sinusitis and gynaecological infections, and for the prophylaxis or treatment of surgical infections. The clinical efficacy of cefodizime in comparison with other third generation cephalosporins is superior to that predicted from in vitro results. This superior activity of cefodizime may be related to the relatively long elimination half-life of the drug or its ability to modify some functions of the immune system--a potentially important finding awaiting further investigation. Cefodizime is well tolerated and has a tolerability profile similar to other members of its class with systemic adverse events being primarily gastrointestinal or dermatological. Thus, limited comparative studies indicate cefodizime has the potential to become a useful alternative to current antimicrobial therapy for the treatment of a variety of infections. Cefodizime may be more convenient to administer than some other agents of its class as it may be given once or twice daily. While there are no trials comparing cefodizime to other third generation cephalosporins in immunosuppressed populations, preliminary information indicates cefodizime may be useful in this group."} {"id": "PMID:1280569", "title": "Bepridil. A review of its pharmacological properties and therapeutic use in stable angina pectoris.", "content": "Bepridil is a calcium antagonist with direct negative chronotropic, dromotropic, inotropic and vasodilatory actions which reduces myocardial oxygen consumption and increases coronary blood flow, leading to a significant anti-ischaemic and antianginal effect in the absence of reflex tachycardia. In contrast to other calcium channel blockers, bepridil produces only modest peripheral vasodilatation and displays weak antihypertensive activity. Its plasma elimination half-life of 1 to 2 days permits once daily administration. Results of short term clinical trials have shown bepridil to be of comparable efficacy to nifedipine, verapamil, diltiazem, propranolol and nadolol in decreasing the frequency of anginal attacks and consumption of nitroglycerin (glyceryl trinitrate) in patients with stable angina. Bepridil is more effective than nifedipine in improving exercise performance in patients with stable angina. Although bepridil proved superior to diltiazem in improving exercise performance in patients refractory to diltiazem, further studies are required to confirm the efficacy of bepridil in patients refractory to, or intolerant of, other antianginal agents. Bepridil in therapeutic doses is well tolerated, and appears to have a similar adverse effect profile to the established calcium antagonists. However, rate-dependent prolongation of the QTc interval and development of torsade de pointes have been associated with the use of bepridil. Therefore, bepridil is contraindicated in patients with hypokalaemia, those receiving other drugs that may prolong the QT interval, and those with congenital QT interval prolongation. Future clinical research will help to further define the position of bepridil as an antianginal treatment relative to the traditional calcium antagonists; in the interim, bepridil is indicated for the treatment of patients with angina refractory to or intolerant of other agents.", "contents": "Bepridil. A review of its pharmacological properties and therapeutic use in stable angina pectoris. Bepridil is a calcium antagonist with direct negative chronotropic, dromotropic, inotropic and vasodilatory actions which reduces myocardial oxygen consumption and increases coronary blood flow, leading to a significant anti-ischaemic and antianginal effect in the absence of reflex tachycardia. In contrast to other calcium channel blockers, bepridil produces only modest peripheral vasodilatation and displays weak antihypertensive activity. Its plasma elimination half-life of 1 to 2 days permits once daily administration. Results of short term clinical trials have shown bepridil to be of comparable efficacy to nifedipine, verapamil, diltiazem, propranolol and nadolol in decreasing the frequency of anginal attacks and consumption of nitroglycerin (glyceryl trinitrate) in patients with stable angina. Bepridil is more effective than nifedipine in improving exercise performance in patients with stable angina. Although bepridil proved superior to diltiazem in improving exercise performance in patients refractory to diltiazem, further studies are required to confirm the efficacy of bepridil in patients refractory to, or intolerant of, other antianginal agents. Bepridil in therapeutic doses is well tolerated, and appears to have a similar adverse effect profile to the established calcium antagonists. However, rate-dependent prolongation of the QTc interval and development of torsade de pointes have been associated with the use of bepridil. Therefore, bepridil is contraindicated in patients with hypokalaemia, those receiving other drugs that may prolong the QT interval, and those with congenital QT interval prolongation. Future clinical research will help to further define the position of bepridil as an antianginal treatment relative to the traditional calcium antagonists; in the interim, bepridil is indicated for the treatment of patients with angina refractory to or intolerant of other agents."} {"id": "PMID:1280570", "title": "Nadroparin calcium. A review of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disorders.", "content": "Nadroparin calcium is a low molecular weight heparin with a mean molecular weight of 4.5 kD. Compared with unfractionated heparin, nadroparin calcium has a greater ratio of anti-factor Xa/anti-factor IIa activity. Nadroparin calcium has a longer half-life and greater bioavailability than unfractionated heparin and can be administered by subcutaneous injection once daily for prophylaxis and twice daily for treatment. In clinical trials, nadroparin calcium has been shown to be at least as effective as unfractionated heparin in preventing deep venous thrombosis (DVT) after various surgical procedures including major orthopaedic and abdominal surgery, and in maintaining the patency of the extracorporeal circulation in adults and children undergoing haemodialysis. Nadroparin calcium is well tolerated, the most common adverse event associated with its use being the development of minor haematoma at the operative incision site. In postmarketing surveillance data to date, the incidence of major haemorrhage related to nadroparin calcium use has been very low (< 1%). Nadroparin calcium has also been associated with a very low incidence of thrombocytopenia (< 0.001%). Thus, nadroparin calcium is an effective alternative to unfractionated heparin in the prophylaxis or treatment of thromboembolic venous events, with the advantages of more convenient administration and a lower incidence of thrombocytopenia.", "contents": "Nadroparin calcium. A review of its pharmacology and clinical applications in the prevention and treatment of thromboembolic disorders. Nadroparin calcium is a low molecular weight heparin with a mean molecular weight of 4.5 kD. Compared with unfractionated heparin, nadroparin calcium has a greater ratio of anti-factor Xa/anti-factor IIa activity. Nadroparin calcium has a longer half-life and greater bioavailability than unfractionated heparin and can be administered by subcutaneous injection once daily for prophylaxis and twice daily for treatment. In clinical trials, nadroparin calcium has been shown to be at least as effective as unfractionated heparin in preventing deep venous thrombosis (DVT) after various surgical procedures including major orthopaedic and abdominal surgery, and in maintaining the patency of the extracorporeal circulation in adults and children undergoing haemodialysis. Nadroparin calcium is well tolerated, the most common adverse event associated with its use being the development of minor haematoma at the operative incision site. In postmarketing surveillance data to date, the incidence of major haemorrhage related to nadroparin calcium use has been very low (< 1%). Nadroparin calcium has also been associated with a very low incidence of thrombocytopenia (< 0.001%). Thus, nadroparin calcium is an effective alternative to unfractionated heparin in the prophylaxis or treatment of thromboembolic venous events, with the advantages of more convenient administration and a lower incidence of thrombocytopenia."} {"id": "PMID:1280571", "title": "Cefpodoxime proxetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential.", "content": "Cefpodoxime proxetil is an orally administered prodrug which is absorbed and de-esterified by the intestinal mucosa to release the third generation cephalosporin, cefpodoxime. Cefpodoxime is stable towards the most commonly found plasmid-mediated beta-lactamases and the drug has a broad spectrum of antibacterial activity encompassing both Gram-negative and Gram-positive bacteria, rendering it a possible option for empirical use in a wide range of community acquired infections in both adult and paediatric patients. The extended plasma half-life of cefpodoxime (1.9 to 3.7 h) permits twice daily administration. In comparative trials, twice daily cefpodoxime proxetil (dose equivalent cefpodoxime 100 to 400 mg) was as effective as a 3- to 4-times daily regimen of phenoxymethylpenicillin in pharyngotonsillitis, as well as thrice daily amoxicillin (with or without clavulanic acid) or cefaclor against infections of the ear, the upper and lower respiratory tract, the urinary tract and those of the skin and soft tissues. The latter reflects the enhanced antistaphylococcal activity of cefpodoxime, which distinguishes it from other orally active third generation cephalosporins such as cefixime. Most notably, an oral regimen of cefpodoxime proxetil was as efficacious as parenterally administered ceftriaxone for the treatment of bronchopneumonia in hospitalised patients at risk due to the presence of underlying diseases, addictions or advancing age. A single oral dose of cefpodoxime was also as efficacious as ceftriaxone in uncomplicated anogenital gonococcal infections. Cefpodoxime proxetil is generally well tolerated, with mild to moderate gastrointestinal disturbances occurring in 4 to 15% of patients treated with therapeutic doses. Thus, a convenient twice daily oral regimen of cefpodoxime proxetil can be prescribed as an effective alternative to established beta-lactam therapies in the empirical outpatient treatment of infections of the respiratory and urinary tracts as well as those of the skin and soft tissues.", "contents": "Cefpodoxime proxetil. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential. Cefpodoxime proxetil is an orally administered prodrug which is absorbed and de-esterified by the intestinal mucosa to release the third generation cephalosporin, cefpodoxime. Cefpodoxime is stable towards the most commonly found plasmid-mediated beta-lactamases and the drug has a broad spectrum of antibacterial activity encompassing both Gram-negative and Gram-positive bacteria, rendering it a possible option for empirical use in a wide range of community acquired infections in both adult and paediatric patients. The extended plasma half-life of cefpodoxime (1.9 to 3.7 h) permits twice daily administration. In comparative trials, twice daily cefpodoxime proxetil (dose equivalent cefpodoxime 100 to 400 mg) was as effective as a 3- to 4-times daily regimen of phenoxymethylpenicillin in pharyngotonsillitis, as well as thrice daily amoxicillin (with or without clavulanic acid) or cefaclor against infections of the ear, the upper and lower respiratory tract, the urinary tract and those of the skin and soft tissues. The latter reflects the enhanced antistaphylococcal activity of cefpodoxime, which distinguishes it from other orally active third generation cephalosporins such as cefixime. Most notably, an oral regimen of cefpodoxime proxetil was as efficacious as parenterally administered ceftriaxone for the treatment of bronchopneumonia in hospitalised patients at risk due to the presence of underlying diseases, addictions or advancing age. A single oral dose of cefpodoxime was also as efficacious as ceftriaxone in uncomplicated anogenital gonococcal infections. Cefpodoxime proxetil is generally well tolerated, with mild to moderate gastrointestinal disturbances occurring in 4 to 15% of patients treated with therapeutic doses. Thus, a convenient twice daily oral regimen of cefpodoxime proxetil can be prescribed as an effective alternative to established beta-lactam therapies in the empirical outpatient treatment of infections of the respiratory and urinary tracts as well as those of the skin and soft tissues."} {"id": "PMID:1280572", "title": "Pathophysiology of diabetes. A review of selected recent developments and their impact on treatment.", "content": "Recent developments in epidemiology, physiology, anatomy and molecular biology have greatly increased our knowledge of the aetiology and immunological mechanisms involved in diabetes mellitus. This understanding has, in turn, facilitated progress in the diagnosis and treatment of the disease. It is generally accepted that both genetic and environmental factors have a role in the pathogenesis of insulin- and non-insulin-dependent diabetes mellitus. The contribution of insulin resistance or decreased insulin secretion to the pathogenesis of non-insulin-dependent diabetes remains controversial but it is likely that both have a role to play. Counterregulatory hormones, principally adrenaline (epinephrine) and glucagon, prevent blood glucose levels falling to extreme levels by antagonising the effect of insulin hypoglycaemia, and inducing hepatic glucose production. Patients with insulin-dependent diabetes frequently exhibit impaired glucose counterregulation and, although its aetiology is uncertain in some patients, intensification of insulin therapy per se has been implicated. Secondary failure of oral hypoglycaemic agents in patients with non-insulin-dependent diabetes is a major and often inevitable problem, necessitating combined use of sulphonylurea and insulin in most patients. Recently, new treatments for patients with diabetes have been developed, including insulin analogues administered by a variety of novel methods, pancreatic grafts and transplantation of islet cells. Although promising, the clinical viability of these techniques remains to be demonstrated.", "contents": "Pathophysiology of diabetes. A review of selected recent developments and their impact on treatment. Recent developments in epidemiology, physiology, anatomy and molecular biology have greatly increased our knowledge of the aetiology and immunological mechanisms involved in diabetes mellitus. This understanding has, in turn, facilitated progress in the diagnosis and treatment of the disease. It is generally accepted that both genetic and environmental factors have a role in the pathogenesis of insulin- and non-insulin-dependent diabetes mellitus. The contribution of insulin resistance or decreased insulin secretion to the pathogenesis of non-insulin-dependent diabetes remains controversial but it is likely that both have a role to play. Counterregulatory hormones, principally adrenaline (epinephrine) and glucagon, prevent blood glucose levels falling to extreme levels by antagonising the effect of insulin hypoglycaemia, and inducing hepatic glucose production. Patients with insulin-dependent diabetes frequently exhibit impaired glucose counterregulation and, although its aetiology is uncertain in some patients, intensification of insulin therapy per se has been implicated. Secondary failure of oral hypoglycaemic agents in patients with non-insulin-dependent diabetes is a major and often inevitable problem, necessitating combined use of sulphonylurea and insulin in most patients. Recently, new treatments for patients with diabetes have been developed, including insulin analogues administered by a variety of novel methods, pancreatic grafts and transplantation of islet cells. Although promising, the clinical viability of these techniques remains to be demonstrated."} {"id": "PMID:1280573", "title": "Nutritional recommendations for diabetic patients and treatment with alpha-glucosidase inhibitors.", "content": "Adjunctive treatment with acarbose (possibLy together with sulphonylurea or insulin treatment) can be effectively utilised to achieve blood glucose control if postprandial hyperglycaemia is a problem and cannot be sufficiently controlled by dietary modifications. The alpha-glucosidase inhibitor, acarbose, should be taken with meals that are rich in complex carbohydrates and low in simple sugars, as recommended by diabetes associations, to achieve the greatest possible benefit from treatment.", "contents": "Nutritional recommendations for diabetic patients and treatment with alpha-glucosidase inhibitors. Adjunctive treatment with acarbose (possibLy together with sulphonylurea or insulin treatment) can be effectively utilised to achieve blood glucose control if postprandial hyperglycaemia is a problem and cannot be sufficiently controlled by dietary modifications. The alpha-glucosidase inhibitor, acarbose, should be taken with meals that are rich in complex carbohydrates and low in simple sugars, as recommended by diabetes associations, to achieve the greatest possible benefit from treatment."} {"id": "PMID:1280574", "title": "Oral antidiabetic agents. The emergence of alpha-glucosidase inhibitors.", "content": "Hyperglycaemia in patients with non-insulin-dependent diabetes mellitus (NIDDM) results from impaired insulin action and/or deficient insulin secretion. These abnormalities lead to increased hepatic glucose production, the primary cause of fasting hyperglycaemia, and decreased peripheral glucose uptake, the major mechanism responsible for postprandial hyperglycaemia. Hyperglycaemia in patients with NIDDM can be decreased by several different mechanisms: (1) a decrease in nutrient ingestion; (2) an increase in insulin secretion; (3) a decrease in hepatic glucose production; (4) an increase in peripheral glucose uptake. Oral agents used to treat NIDDM operate through 1 or more of the above mechanisms. alpha-Glucosidase inhibitors, a new class of drugs that delay carbohydrate digestion and absorption, reduce postprandial glycaemic rises by about 3 mmol/L. Metformin decreases fasting and postprandial hyperglycaemia through increasing glucose uptake and perhaps decreasing appetite. Sulphonylureas lower hyperglycaemia by increasing insulin secretion and to a lesser degree potentiating insulin action on the liver and peripheral tissues. alpha-Glucosidase inhibitors are particularly useful as primary therapy for patients with mild to moderate hyperglycaemia and in those patients who may be at risk for hypoglycaemia or lactic acidosis. Sulphonylureas are indicated for the more severely hyperglycaemic NIDDM patients who are not yet candidates for insulin therapy. Metformin is useful in obese moderately hyperglycaemic NIDDM patients. These oral agents can be used in combination to give better glycaemic control than is possible with each alone.", "contents": "Oral antidiabetic agents. The emergence of alpha-glucosidase inhibitors. Hyperglycaemia in patients with non-insulin-dependent diabetes mellitus (NIDDM) results from impaired insulin action and/or deficient insulin secretion. These abnormalities lead to increased hepatic glucose production, the primary cause of fasting hyperglycaemia, and decreased peripheral glucose uptake, the major mechanism responsible for postprandial hyperglycaemia. Hyperglycaemia in patients with NIDDM can be decreased by several different mechanisms: (1) a decrease in nutrient ingestion; (2) an increase in insulin secretion; (3) a decrease in hepatic glucose production; (4) an increase in peripheral glucose uptake. Oral agents used to treat NIDDM operate through 1 or more of the above mechanisms. alpha-Glucosidase inhibitors, a new class of drugs that delay carbohydrate digestion and absorption, reduce postprandial glycaemic rises by about 3 mmol/L. Metformin decreases fasting and postprandial hyperglycaemia through increasing glucose uptake and perhaps decreasing appetite. Sulphonylureas lower hyperglycaemia by increasing insulin secretion and to a lesser degree potentiating insulin action on the liver and peripheral tissues. alpha-Glucosidase inhibitors are particularly useful as primary therapy for patients with mild to moderate hyperglycaemia and in those patients who may be at risk for hypoglycaemia or lactic acidosis. Sulphonylureas are indicated for the more severely hyperglycaemic NIDDM patients who are not yet candidates for insulin therapy. Metformin is useful in obese moderately hyperglycaemic NIDDM patients. These oral agents can be used in combination to give better glycaemic control than is possible with each alone."} {"id": "PMID:1280575", "title": "Management of non-insulin-dependent diabetes mellitus.", "content": "The initial management of non-insulin-dependent diabetes mellitus (NIDDM) should include patient education, dietary counselling and, when feasible, individualised physical activity. It is only when such measures fail that drug therapy should be considered. Dietary management of NIDDM includes a restriction in calories, and these should be appropriately distributed as carbohydrates, lipids and proteins. Supplementation of the diet with soluble fibre and supplementation with magnesium salts if hypomagnesaemia is demonstrated, is recommended. However, supplementation with fish oils or with fish oil-derived omega-3 fatty acids is not currently recommended. Oral drug therapies used in NIDDM include sulphonylurea derivatives, which are a first-line treatment in patients who are not grossly obese, metformin, which is the treatment of choice for obese patients, and alpha-glucosidase inhibitors such as acarbose, which are used mainly to reduce postprandial blood glucose peaks. These types of drugs can be used alone or in combination. Insulin therapy may be required to achieve adequate control of blood glucose levels in some patients. In several instances, it is suggested that insulin therapy be combined with sulphonylureas (essentially when residual insulin secretion is present), with metformin, or with alpha-glucosidase inhibitors. The treatment of disorders associated with NIDDM, such as obesity, hypertension or hyperlipidaemia, requires particular attention in diabetic patients, since some drugs can adversely affect glycaemic control. Oral drugs for the treatment of NIDDM include sulphonylurea derivatives used in first-line treatment in patients who are not grossly obese, metformin, which is often the treatment of choice for obese patients and, more recently, the alpha-glucosidase inhibitors, such as acarbose, which are effective in reducing the postprandial rise in blood glucose.", "contents": "Management of non-insulin-dependent diabetes mellitus. The initial management of non-insulin-dependent diabetes mellitus (NIDDM) should include patient education, dietary counselling and, when feasible, individualised physical activity. It is only when such measures fail that drug therapy should be considered. Dietary management of NIDDM includes a restriction in calories, and these should be appropriately distributed as carbohydrates, lipids and proteins. Supplementation of the diet with soluble fibre and supplementation with magnesium salts if hypomagnesaemia is demonstrated, is recommended. However, supplementation with fish oils or with fish oil-derived omega-3 fatty acids is not currently recommended. Oral drug therapies used in NIDDM include sulphonylurea derivatives, which are a first-line treatment in patients who are not grossly obese, metformin, which is the treatment of choice for obese patients, and alpha-glucosidase inhibitors such as acarbose, which are used mainly to reduce postprandial blood glucose peaks. These types of drugs can be used alone or in combination. Insulin therapy may be required to achieve adequate control of blood glucose levels in some patients. In several instances, it is suggested that insulin therapy be combined with sulphonylureas (essentially when residual insulin secretion is present), with metformin, or with alpha-glucosidase inhibitors. The treatment of disorders associated with NIDDM, such as obesity, hypertension or hyperlipidaemia, requires particular attention in diabetic patients, since some drugs can adversely affect glycaemic control. Oral drugs for the treatment of NIDDM include sulphonylurea derivatives used in first-line treatment in patients who are not grossly obese, metformin, which is often the treatment of choice for obese patients and, more recently, the alpha-glucosidase inhibitors, such as acarbose, which are effective in reducing the postprandial rise in blood glucose."} {"id": "PMID:1280576", "title": "Management of insulin-dependent diabetes mellitus.", "content": "Insulin therapy has been lifesaving for patients with insulin-dependent diabetes mellitus. Unfortunately, longer lifespan has unmasked microvascular, neurological and macrovascular complications that result in profound morbidity and increased mortality. Driven by the conviction that better physiological control of glycaemic levels will prevent and/or ameliorate long term complications, and by the desire to make diabetes care as user-friendly as possible, clinical research efforts have led to the development of new treatment methods with the aim of achieving near normal metabolic control. Such methods include the use of self monitoring, multiple daily insulin injection regimens, external and implantable insulin pumps, and whole organ pancreas and isolated islet cell transplantation. In addition, dietary manipulation, including the use of alpha-glucosidase inhibitors, has played a role in controlling glycaemia.", "contents": "Management of insulin-dependent diabetes mellitus. Insulin therapy has been lifesaving for patients with insulin-dependent diabetes mellitus. Unfortunately, longer lifespan has unmasked microvascular, neurological and macrovascular complications that result in profound morbidity and increased mortality. Driven by the conviction that better physiological control of glycaemic levels will prevent and/or ameliorate long term complications, and by the desire to make diabetes care as user-friendly as possible, clinical research efforts have led to the development of new treatment methods with the aim of achieving near normal metabolic control. Such methods include the use of self monitoring, multiple daily insulin injection regimens, external and implantable insulin pumps, and whole organ pancreas and isolated islet cell transplantation. In addition, dietary manipulation, including the use of alpha-glucosidase inhibitors, has played a role in controlling glycaemia."} {"id": "PMID:1280577", "title": "Safety profile of acarbose, an alpha-glucosidase inhibitor.", "content": "Acarbose, an alpha-glucosidase inhibitor, delays absorption of carbohydrate in the gut, thereby lowering postprandial glucose levels. Safety data on this drug have been gathered in a series of studies on animals and in extensive clinical trials in humans. Although an initial long term feeding study in rats showed an excess of renal tumours at very high dosages of acarbose (up to 300 mg/kg bodyweight daily), further evaluation with similar studies in rats, hamsters, and dogs indicated that the problem was related to carbohydrate malabsorption. With adequate glucose intake and in gavage studies, no difference in tumour incidence between placebo- and acarbose-treated groups was seen. From 1976 to 1989, safety data on acarbose were obtained in approximately 8800 patients in 2 separate groups of clinical trials, the Bayer International Clinical Data Pool and the American phase III trials. Almost all adverse experiences, as reported by 56 to 76% of patients on acarbose vs 32 to 37% of patients on placebo, were related to the digestive system and included diarrhoea, flatulence, bloating and nausea. Most symptoms were of mild to moderate intensity and tended to improve with time. In the American trials a small but significant increase in liver transaminases was seen, 3.8% in acarbose-treated patients vs 0.9% in controls together with a 1% increase in anaemia in the acarbose group. Overall, acarbose was well tolerated and the adverse experience profile was clinically acceptable.", "contents": "Safety profile of acarbose, an alpha-glucosidase inhibitor. Acarbose, an alpha-glucosidase inhibitor, delays absorption of carbohydrate in the gut, thereby lowering postprandial glucose levels. Safety data on this drug have been gathered in a series of studies on animals and in extensive clinical trials in humans. Although an initial long term feeding study in rats showed an excess of renal tumours at very high dosages of acarbose (up to 300 mg/kg bodyweight daily), further evaluation with similar studies in rats, hamsters, and dogs indicated that the problem was related to carbohydrate malabsorption. With adequate glucose intake and in gavage studies, no difference in tumour incidence between placebo- and acarbose-treated groups was seen. From 1976 to 1989, safety data on acarbose were obtained in approximately 8800 patients in 2 separate groups of clinical trials, the Bayer International Clinical Data Pool and the American phase III trials. Almost all adverse experiences, as reported by 56 to 76% of patients on acarbose vs 32 to 37% of patients on placebo, were related to the digestive system and included diarrhoea, flatulence, bloating and nausea. Most symptoms were of mild to moderate intensity and tended to improve with time. In the American trials a small but significant increase in liver transaminases was seen, 3.8% in acarbose-treated patients vs 0.9% in controls together with a 1% increase in anaemia in the acarbose group. Overall, acarbose was well tolerated and the adverse experience profile was clinically acceptable."} {"id": "PMID:1280578", "title": "Preventing long term complications. Implications for combination therapy with acarbose.", "content": "Long term complications continue to be the major source of morbidity and mortality in patients with diabetes. Acarbose could potentially help to reduce diabetic complications if it improved glucose control, reduced lipid levels and hyperinsulinaemia. Acarbose has been shown to effectively reduce postprandial hyperglycaemia and haemoglobin A1c. This effect might be helpful in patients with insulin-dependent diabetes mellitus, as insulin injections do not provide complete control of rises in postprandial glucose levels, and in patients with non-insulin-dependent diabetes mellitus, because it simplifies the treatment programme. If improved control is shown to reduce complications, acarbose may be helpful. Although acarbose does not reduce hyperinsulinaemia, it reduces lipid levels and thus could reduce the risk of atherosclerosis.", "contents": "Preventing long term complications. Implications for combination therapy with acarbose. Long term complications continue to be the major source of morbidity and mortality in patients with diabetes. Acarbose could potentially help to reduce diabetic complications if it improved glucose control, reduced lipid levels and hyperinsulinaemia. Acarbose has been shown to effectively reduce postprandial hyperglycaemia and haemoglobin A1c. This effect might be helpful in patients with insulin-dependent diabetes mellitus, as insulin injections do not provide complete control of rises in postprandial glucose levels, and in patients with non-insulin-dependent diabetes mellitus, because it simplifies the treatment programme. If improved control is shown to reduce complications, acarbose may be helpful. Although acarbose does not reduce hyperinsulinaemia, it reduces lipid levels and thus could reduce the risk of atherosclerosis."} {"id": "PMID:1280579", "title": "Effect of ambient oxygen concentration upon the acute toxicity of chlorophenols and heavy metals to the groundwater copepod Parastenocaris germanica (Crustacea).", "content": "Acute static toxicity experiments have been performed under normoxic and hypoxic conditions. The test animals used were adults of the groundwater-adapted copepod Parastenocaris germanica. The animals originated from a sandy, gravelly phreatic aquifer of the Meuse valley in The Netherlands. Toxicants applied were pentachlorophenol, 3,4-dichlorophenol, zinc, and cadmium. The results were statistically evaluated by a log-logistic model. LC50 and LC5 values with 95% confidence limits were calculated. Response models of application under both oxygen conditions were compared. The influence of ambient oxygen concentration on sensitivity appeared to be very small; only in the case of pentachlorophenol were hypoxic and normoxic models slightly but significantly different. Comparisons with the sensitivity of other organisms are made and the results are discussed against the specific physiological adaptations of the organisms to groundwater conditions.", "contents": "Effect of ambient oxygen concentration upon the acute toxicity of chlorophenols and heavy metals to the groundwater copepod Parastenocaris germanica (Crustacea). Acute static toxicity experiments have been performed under normoxic and hypoxic conditions. The test animals used were adults of the groundwater-adapted copepod Parastenocaris germanica. The animals originated from a sandy, gravelly phreatic aquifer of the Meuse valley in The Netherlands. Toxicants applied were pentachlorophenol, 3,4-dichlorophenol, zinc, and cadmium. The results were statistically evaluated by a log-logistic model. LC50 and LC5 values with 95% confidence limits were calculated. Response models of application under both oxygen conditions were compared. The influence of ambient oxygen concentration on sensitivity appeared to be very small; only in the case of pentachlorophenol were hypoxic and normoxic models slightly but significantly different. Comparisons with the sensitivity of other organisms are made and the results are discussed against the specific physiological adaptations of the organisms to groundwater conditions."} {"id": "PMID:1280580", "title": "Induction and characterization of cytochromes P450IA and -IIB in the newt, Pleurodeles waltl.", "content": "The newt (Pleurodeles waltl) is an amphibian species used in a mutagenicity test (micronucleus). This study was carried out to establish if the inducibility of hepatic cytochromes P450 of this species is similar to that of the rat. Our results showed that the newt is characterized by a lower level of hepatic cytochrome P450-dependent activities than the rat. Variations of enzymatic activities according to sex and season were observed. Specific activities in newt were characterized by an almost complete insensitivity to induction by phenobarbital pretreatment. On the other hand, pretreatment by 3-methylcholanthrene resulted in an increase in the metabolism of several hydroxycoumarin and resorufin derivatives, similar to the effects observed in rat liver. Occurrence of specific forms of cytochromes P450 was assessed by specific antibodies.", "contents": "Induction and characterization of cytochromes P450IA and -IIB in the newt, Pleurodeles waltl. The newt (Pleurodeles waltl) is an amphibian species used in a mutagenicity test (micronucleus). This study was carried out to establish if the inducibility of hepatic cytochromes P450 of this species is similar to that of the rat. Our results showed that the newt is characterized by a lower level of hepatic cytochrome P450-dependent activities than the rat. Variations of enzymatic activities according to sex and season were observed. Specific activities in newt were characterized by an almost complete insensitivity to induction by phenobarbital pretreatment. On the other hand, pretreatment by 3-methylcholanthrene resulted in an increase in the metabolism of several hydroxycoumarin and resorufin derivatives, similar to the effects observed in rat liver. Occurrence of specific forms of cytochromes P450 was assessed by specific antibodies."} {"id": "PMID:1280581", "title": "Toxic effects of omega chrome red ME and its treatment by adsorption.", "content": "Toxic effects of Omega Chrome Red ME, a popular textile dye, on the nitrogen fixing cyanobacterium Nostoc calcicola were studied. The growth of N. calcicola was found to be suppressed at 10 and 20 mg liter-1 initial concentrations of dye, whereas a low initial concentration of 5 mg liter-1 slightly favors growth. Removal of the dye was carried out by adsorption using some cheap and unconventional adsorbents like coal, fly ash, wollastonite, and china clay. It has been observed that, in all cases, the low adsorbate concentration, the low temperature, and an acidic medium favor the dye removal process. The process of uptake follows first-order adsorption rate expression and obeys Langmuir's model of adsorption. The removal process is also partially diffusion controlled. Thermodynamic and pH studies were run to explain the results.", "contents": "Toxic effects of omega chrome red ME and its treatment by adsorption. Toxic effects of Omega Chrome Red ME, a popular textile dye, on the nitrogen fixing cyanobacterium Nostoc calcicola were studied. The growth of N. calcicola was found to be suppressed at 10 and 20 mg liter-1 initial concentrations of dye, whereas a low initial concentration of 5 mg liter-1 slightly favors growth. Removal of the dye was carried out by adsorption using some cheap and unconventional adsorbents like coal, fly ash, wollastonite, and china clay. It has been observed that, in all cases, the low adsorbate concentration, the low temperature, and an acidic medium favor the dye removal process. The process of uptake follows first-order adsorption rate expression and obeys Langmuir's model of adsorption. The removal process is also partially diffusion controlled. Thermodynamic and pH studies were run to explain the results."} {"id": "PMID:1280583", "title": "The effect of Cu (II) on the electro-olfactogram (EOG) of the Atlantic salmon (Salmo salar L) in artificial freshwater of varying inorganic carbon concentrations.", "content": "The effect of inorganic copper species was studied by recording the receptor potential, electro-olfactogram (EOG), from the olfactory epithelium of Atlantic salmon (Salmo salar L). In a series of experiments, the olfactory organ was irrigated with aqueous copper solutions with concentrations of the free cupric ion (Cu2+) ranging from 0.2 to 9.7 microM. The diverse copper species were created by varying the amount of bicarbonate (NaHCO3) in artificial freshwater solutions of equal total copper concentrations. In general, these copper solutions induced a slow depolarization of the baseline followed by a hyperpolarization. The amplitudes of these variations in baseline potentials increased with increasing concentrations of Cu2+ ion, i.e., decreasing concentrations of NaHCO3. Stimulating the olfactory epithelium with L-alanine during the copper exposure evoked atypical EOG responses. The amplitudes and form of the EOGs changed drastically with increasing Cu2+ concentrations, with significant correlation between the reduction in EOG amplitudes and the Cu2+ concentration. The results indicate that among the copper species tested the toxic effect is caused mainly by the dissolved Cu2+ ion. The results also suggest that the Cu2+ ion exerts its toxic effects on the transduction mechanisms of the olfactory receptor cells. The different EOG profiles obtained in response to varying Cu2+ concentrations indicate that this ion affects the transduction mechanisms at different stages.", "contents": "The effect of Cu (II) on the electro-olfactogram (EOG) of the Atlantic salmon (Salmo salar L) in artificial freshwater of varying inorganic carbon concentrations. The effect of inorganic copper species was studied by recording the receptor potential, electro-olfactogram (EOG), from the olfactory epithelium of Atlantic salmon (Salmo salar L). In a series of experiments, the olfactory organ was irrigated with aqueous copper solutions with concentrations of the free cupric ion (Cu2+) ranging from 0.2 to 9.7 microM. The diverse copper species were created by varying the amount of bicarbonate (NaHCO3) in artificial freshwater solutions of equal total copper concentrations. In general, these copper solutions induced a slow depolarization of the baseline followed by a hyperpolarization. The amplitudes of these variations in baseline potentials increased with increasing concentrations of Cu2+ ion, i.e., decreasing concentrations of NaHCO3. Stimulating the olfactory epithelium with L-alanine during the copper exposure evoked atypical EOG responses. The amplitudes and form of the EOGs changed drastically with increasing Cu2+ concentrations, with significant correlation between the reduction in EOG amplitudes and the Cu2+ concentration. The results indicate that among the copper species tested the toxic effect is caused mainly by the dissolved Cu2+ ion. The results also suggest that the Cu2+ ion exerts its toxic effects on the transduction mechanisms of the olfactory receptor cells. The different EOG profiles obtained in response to varying Cu2+ concentrations indicate that this ion affects the transduction mechanisms at different stages."} {"id": "PMID:1280584", "title": "Short-term effect of a toxicant on scope for change in ascendency in a microcosm community.", "content": "A need in the field of toxicity testing is the development of parallel tests applicable to all levels of biological organization: single-species tests alone cannot predict effects at ecosystem levels. Scope for change in ascendency (SfCA) is a comparative index applicable to the short-term assessment of stress effects on any biological system. The SfCA of a community, defined by analogy to scope for growth of an organism, is the balance of ascendency (network size and organization) of population inputs and outputs. It takes into account the interrelated processes of growth and development, both of which can be affected by stress factors. To illustrate this approach, the effect of atrazine on SfCA of a simple epilimnetic microcosm community was investigated. Simultaneous, short-term measurements of all carbon flows between populations were made and SfCA was calculated. Compounded effects of stress on populations, measured as a relative drop in community SfCA in the presence of atrazine, were observed within 2-3 weeks. This indicates that SfCA may be useful as a comparative index for the short-term assessment of perturbation effects. A refinement of the methodology for measuring resource flows at levels other than the organism would allow full advantage of this assessment tool to be taken.", "contents": "Short-term effect of a toxicant on scope for change in ascendency in a microcosm community. A need in the field of toxicity testing is the development of parallel tests applicable to all levels of biological organization: single-species tests alone cannot predict effects at ecosystem levels. Scope for change in ascendency (SfCA) is a comparative index applicable to the short-term assessment of stress effects on any biological system. The SfCA of a community, defined by analogy to scope for growth of an organism, is the balance of ascendency (network size and organization) of population inputs and outputs. It takes into account the interrelated processes of growth and development, both of which can be affected by stress factors. To illustrate this approach, the effect of atrazine on SfCA of a simple epilimnetic microcosm community was investigated. Simultaneous, short-term measurements of all carbon flows between populations were made and SfCA was calculated. Compounded effects of stress on populations, measured as a relative drop in community SfCA in the presence of atrazine, were observed within 2-3 weeks. This indicates that SfCA may be useful as a comparative index for the short-term assessment of perturbation effects. A refinement of the methodology for measuring resource flows at levels other than the organism would allow full advantage of this assessment tool to be taken."} {"id": "PMID:1280585", "title": "Modulatory actions of ovine luteinizing hormone-releasing hormone and Mystus gonadotropin on gamma-BHC-induced changes in lipid levels in the freshwater catfish, Heteropneustes fossilis.", "content": "Female specimens of Heteropneustes fossilis were exposed to a sublethal concentration of gamma-BHC (16 mg/liter) for 4 weeks during the preparatory and prespawning phases of their annual reproductive cycle. The effect of gamma-BHC on free fatty acids (FFA), monoglycerides (MG), diglycerides (DG), and triglycerides (TG) was monitored. gamma-BHC in general was inhibitory to lipogenesis during both of the reproductively active phases as judged by decreased levels of FFA, MG, DG, and TG. Lower doses of ovine luteinizing hormone-releasing hormone (oLH-RH) and Mystus gonadotropin (mGTH) were ineffective in modulating the impact of gamma-BHC; however, their higher doses effectively revoked the impact of gamma-BHC. From the evidence obtained here, it is concluded that gamma-BHC suppressed the action of oLH-RH and mGTH and affected lipogenesis in this species.", "contents": "Modulatory actions of ovine luteinizing hormone-releasing hormone and Mystus gonadotropin on gamma-BHC-induced changes in lipid levels in the freshwater catfish, Heteropneustes fossilis. Female specimens of Heteropneustes fossilis were exposed to a sublethal concentration of gamma-BHC (16 mg/liter) for 4 weeks during the preparatory and prespawning phases of their annual reproductive cycle. The effect of gamma-BHC on free fatty acids (FFA), monoglycerides (MG), diglycerides (DG), and triglycerides (TG) was monitored. gamma-BHC in general was inhibitory to lipogenesis during both of the reproductively active phases as judged by decreased levels of FFA, MG, DG, and TG. Lower doses of ovine luteinizing hormone-releasing hormone (oLH-RH) and Mystus gonadotropin (mGTH) were ineffective in modulating the impact of gamma-BHC; however, their higher doses effectively revoked the impact of gamma-BHC. From the evidence obtained here, it is concluded that gamma-BHC suppressed the action of oLH-RH and mGTH and affected lipogenesis in this species."} {"id": "PMID:1280586", "title": "A comparison of test systems for assessing effects of metals on isopod ecological functions.", "content": "The effects of metals on the isopod Porcellio scaber and the implication of metal pollution for the functioning of isopods in soil decomposition processes were determined. The experiments were carried out using two test systems, a simple test container without natural substrate and a micro-ecosystem with leaf litter, the latter being more comparable to the field situation. Metals were offered to the isopods by feeding artificially contaminated litter and litter from contaminated field sites. The Cd concentrations in isopods in test containers with ground litter as food were similar to those in isopods in micro-ecosystems with intact leaves as food. Exposure to artificially contaminated litter with Cd alone or litter from contaminated field sites with Cd, Pb, Zn, and Cu resulted in comparable Cd concentrations in the isopods. Growth of the isopods was not affected by Cd or by the combination of Cd, Pb, Zn, and Cu, but differed between the test systems. Fragmentation activity of isopods decreased in litter containing 155 nmol/g Cd and 33500 nmol/g Zn, sampled at a contaminated field site. CO2 production from micro-ecosystems decreased at a concentration of 1010 nmol/g Cd, but NH4 and NO3 concentrations in the litter did not respond to Cd. Isopod growth was better in micro-ecosystems. These systems are therefore recommended for ecotoxicity tests using isopods. After comparison with literature data it was concluded that the bioavailability of Cd in laboratory tests is often higher than the bioavailability in the field at the same total concentrations. This may be due to environmental heterogeneity; this gives animals food choice and is absent in many laboratory test systems. For the quantification of a laboratory-field extrapolation factor for general use, more detailed information is needed than is available now.", "contents": "A comparison of test systems for assessing effects of metals on isopod ecological functions. The effects of metals on the isopod Porcellio scaber and the implication of metal pollution for the functioning of isopods in soil decomposition processes were determined. The experiments were carried out using two test systems, a simple test container without natural substrate and a micro-ecosystem with leaf litter, the latter being more comparable to the field situation. Metals were offered to the isopods by feeding artificially contaminated litter and litter from contaminated field sites. The Cd concentrations in isopods in test containers with ground litter as food were similar to those in isopods in micro-ecosystems with intact leaves as food. Exposure to artificially contaminated litter with Cd alone or litter from contaminated field sites with Cd, Pb, Zn, and Cu resulted in comparable Cd concentrations in the isopods. Growth of the isopods was not affected by Cd or by the combination of Cd, Pb, Zn, and Cu, but differed between the test systems. Fragmentation activity of isopods decreased in litter containing 155 nmol/g Cd and 33500 nmol/g Zn, sampled at a contaminated field site. CO2 production from micro-ecosystems decreased at a concentration of 1010 nmol/g Cd, but NH4 and NO3 concentrations in the litter did not respond to Cd. Isopod growth was better in micro-ecosystems. These systems are therefore recommended for ecotoxicity tests using isopods. After comparison with literature data it was concluded that the bioavailability of Cd in laboratory tests is often higher than the bioavailability in the field at the same total concentrations. This may be due to environmental heterogeneity; this gives animals food choice and is absent in many laboratory test systems. For the quantification of a laboratory-field extrapolation factor for general use, more detailed information is needed than is available now."} {"id": "PMID:1280587", "title": "Tissue lead concentrations and shot ingestion in nine species of waterbirds from the Camargue (France).", "content": "This study investigates the relationship among lead exposure (shot ingestion), current lead impregnation (liver lead values), current and previous lead impregnation (bone lead values), and lead excretion (feather lead) in nine species of waterbird from the Camargue (Rhone river delta), France. Results indicate that for individuals there is no readily predictable relationship between ingested shot and liver or bone lead concentrations. However, at the \"population\" level, and interspecifically, significant positive relationships exist between the susceptibility to shot ingestion and the degree of lead impregnation. Shoveler (Anas clypeata) proved to be an exception, with a high level of shot ingestion and no elevated tissue lead values. This is probably related to dietary factors. Species with a high degree of current lead contamination tended to be those that had also previously absorbed elevated levels of lead. Feather lead concentrations were not clearly related to the vulnerability of a species to shot ingestion or lead poisoning. There was no significant absorption of arsenic and antimony from gunshot associated with lead absorption.", "contents": "Tissue lead concentrations and shot ingestion in nine species of waterbirds from the Camargue (France). This study investigates the relationship among lead exposure (shot ingestion), current lead impregnation (liver lead values), current and previous lead impregnation (bone lead values), and lead excretion (feather lead) in nine species of waterbird from the Camargue (Rhone river delta), France. Results indicate that for individuals there is no readily predictable relationship between ingested shot and liver or bone lead concentrations. However, at the \"population\" level, and interspecifically, significant positive relationships exist between the susceptibility to shot ingestion and the degree of lead impregnation. Shoveler (Anas clypeata) proved to be an exception, with a high level of shot ingestion and no elevated tissue lead values. This is probably related to dietary factors. Species with a high degree of current lead contamination tended to be those that had also previously absorbed elevated levels of lead. Feather lead concentrations were not clearly related to the vulnerability of a species to shot ingestion or lead poisoning. There was no significant absorption of arsenic and antimony from gunshot associated with lead absorption."} {"id": "PMID:1280588", "title": "Primary chemical and physical characterization of acute toxic components in wastewaters.", "content": "A chemical and physical primary characterization work sheet was developed based on the Microtox test, a bacterial bioluminescence system used as a rapid estimate of acute aquatic toxic effects. Measurements of the variation in light reduction upon different pretreatments provided information about the chemical and physical properties of the main toxic component(s) in test wastewater samples. This primary characterization of a wastewater sample was performed within 1 day. Tests of pure toxic chemical compounds and wastewaters with known and unknown primary toxicants are presented. Outlines to the chemical analysis and identification of toxic components may be deduced from the primary characterization. The provisional characterization may also provide information on wastewater treatment techniques.", "contents": "Primary chemical and physical characterization of acute toxic components in wastewaters. A chemical and physical primary characterization work sheet was developed based on the Microtox test, a bacterial bioluminescence system used as a rapid estimate of acute aquatic toxic effects. Measurements of the variation in light reduction upon different pretreatments provided information about the chemical and physical properties of the main toxic component(s) in test wastewater samples. This primary characterization of a wastewater sample was performed within 1 day. Tests of pure toxic chemical compounds and wastewaters with known and unknown primary toxicants are presented. Outlines to the chemical analysis and identification of toxic components may be deduced from the primary characterization. The provisional characterization may also provide information on wastewater treatment techniques."} {"id": "PMID:1280590", "title": "Cloricromene synergizes with antiplatelet drugs and nitric oxide-like factor derived from rat peritoneal polymorphonuclear cells.", "content": "We report that cloricromene (5-30 microM) inhibited thrombin-induced platelet aggregation and synergized with other antiplatelet compounds. The antiaggregatory effect of subthreshold concentrations of the prostaglandin (PG)I2 analogue, iloprost (0.2 nM), or of sodium nitroprusside (1 micron), acting through a nitric oxide (NO)-like mechanism, was significantly potentiated by co-incubation with cloricromene (5 microM). In addition, cloricromene enhanced the antiplatelet activity of the NO-like factor released by peritoneal rat polymorphonuclear cells. Thus, the present results show that cloricromene possesses direct antiplatelet properties and synergizes with other endogenous as well as exogenous antiplatelet compounds.", "contents": "Cloricromene synergizes with antiplatelet drugs and nitric oxide-like factor derived from rat peritoneal polymorphonuclear cells. We report that cloricromene (5-30 microM) inhibited thrombin-induced platelet aggregation and synergized with other antiplatelet compounds. The antiaggregatory effect of subthreshold concentrations of the prostaglandin (PG)I2 analogue, iloprost (0.2 nM), or of sodium nitroprusside (1 micron), acting through a nitric oxide (NO)-like mechanism, was significantly potentiated by co-incubation with cloricromene (5 microM). In addition, cloricromene enhanced the antiplatelet activity of the NO-like factor released by peritoneal rat polymorphonuclear cells. Thus, the present results show that cloricromene possesses direct antiplatelet properties and synergizes with other endogenous as well as exogenous antiplatelet compounds."} {"id": "PMID:1280591", "title": "CP-96,345 antagonism of NK1 receptors and smoke-induced protein extravasation in relation to its cardiovascular effects.", "content": "The effects of the non-peptide NK1 receptor antagonist, CP-96,345, on cardiovascular homeostasis were investigated in conscious and anaesthetized rats in vivo and on heart function and muscle tonicity of vessels in vitro. CP-96,345 and its enantiomer, CP-96,344, which does not exhibit NK1 receptor-blocking activity when tested at a concentration of 1 microM, significantly decreased blood pressure in conscious rats at a dose of 0.32 mg/kg i.v. CP-96,345 and CP-96,344 additionally reduced heart rate at doses of 1 and 3.2 mg/kg, respectively. Studies in anaesthetized rats showed that ganglionic blockade did not modify the decreases in blood pressure and heart rate elicited by CP-96,345. In the isolated guinea-pig heart, CP-96,345 and CP-96,344 exerted negative chronotropic effects at 10(-7) M; negative inotropic effects were observed at 10(-6) M. At 10(-5) M, both CP-96,345 and CP-96,344 decreased the amplitude of contraction of the rat portal vein, whereas at 10(-4) M, both compounds increased the frequency of contraction of this vessel. CP-96,345, at 5 x 10(-8) M, caused relaxation of precontracted pig coronary arteries. Since both CP-96,345 and CP-96,344 produced similar changes in haemodynamics and in the contractility of vascular and cardiac tissue, the cardiovascular effects of CP-96,345 are probably not related to NK1 receptor antagonism. As only the enantiomer with NK1 antagonistic activity inhibited cigarette smoke-induced plasma protein extravasation in rat trachea, CP-96,345 remains a useful tool for elucidating NK1 receptor-mediated responses, provided CP-96,344 is included as control.", "contents": "CP-96,345 antagonism of NK1 receptors and smoke-induced protein extravasation in relation to its cardiovascular effects. The effects of the non-peptide NK1 receptor antagonist, CP-96,345, on cardiovascular homeostasis were investigated in conscious and anaesthetized rats in vivo and on heart function and muscle tonicity of vessels in vitro. CP-96,345 and its enantiomer, CP-96,344, which does not exhibit NK1 receptor-blocking activity when tested at a concentration of 1 microM, significantly decreased blood pressure in conscious rats at a dose of 0.32 mg/kg i.v. CP-96,345 and CP-96,344 additionally reduced heart rate at doses of 1 and 3.2 mg/kg, respectively. Studies in anaesthetized rats showed that ganglionic blockade did not modify the decreases in blood pressure and heart rate elicited by CP-96,345. In the isolated guinea-pig heart, CP-96,345 and CP-96,344 exerted negative chronotropic effects at 10(-7) M; negative inotropic effects were observed at 10(-6) M. At 10(-5) M, both CP-96,345 and CP-96,344 decreased the amplitude of contraction of the rat portal vein, whereas at 10(-4) M, both compounds increased the frequency of contraction of this vessel. CP-96,345, at 5 x 10(-8) M, caused relaxation of precontracted pig coronary arteries. Since both CP-96,345 and CP-96,344 produced similar changes in haemodynamics and in the contractility of vascular and cardiac tissue, the cardiovascular effects of CP-96,345 are probably not related to NK1 receptor antagonism. As only the enantiomer with NK1 antagonistic activity inhibited cigarette smoke-induced plasma protein extravasation in rat trachea, CP-96,345 remains a useful tool for elucidating NK1 receptor-mediated responses, provided CP-96,344 is included as control."} {"id": "PMID:1280592", "title": "Pharmacological characterization of new cholecystokinin analogues.", "content": "New analogues of cholecystokinin-7 (CCK-7) modified at amino acid residues 5 and 7 were assayed for their effect on gall bladder, pancreatic secretion, food intake (anorectic activity), amount of rearing (sedative activity) and analgesia, as well as their ability to inhibit 125I-CCK-8 binding to pancreatic cell membrane receptors and brain membrane receptors. The results were compared to the activities of standard compounds, CCK-8, cerulein, BOC-CCK-7 (BOC = tertbutyloxycarbonyl) and BOC-[Nle2,Nle5]CCK-7. All analogues exhibited agonistic effects. Their anorectic activity was significantly prolonged.", "contents": "Pharmacological characterization of new cholecystokinin analogues. New analogues of cholecystokinin-7 (CCK-7) modified at amino acid residues 5 and 7 were assayed for their effect on gall bladder, pancreatic secretion, food intake (anorectic activity), amount of rearing (sedative activity) and analgesia, as well as their ability to inhibit 125I-CCK-8 binding to pancreatic cell membrane receptors and brain membrane receptors. The results were compared to the activities of standard compounds, CCK-8, cerulein, BOC-CCK-7 (BOC = tertbutyloxycarbonyl) and BOC-[Nle2,Nle5]CCK-7. All analogues exhibited agonistic effects. Their anorectic activity was significantly prolonged."} {"id": "PMID:1280593", "title": "Atrial natriuretic peptide suppresses renal vasoconstriction induced by angiotensin II and norepinephrine in dogs.", "content": "Atrial natriuretic peptide (ANP, 10 and 50 ng/kg per min), infused into the renal artery, suppressed decreases in renal blood flow induced by intrarenal arterial injection of angiotensin II (Ang II, 25-100 ng) and norepinephrine (NE, 0.25-1 microgram) in anesthetized dogs. Sodium nitroprusside (SNP, 0.1-5.0 micrograms/kg per min) slightly attenuated the blood flow response to Ang II but not the response to NE. 8-Bromo cyclic GMP (8bcGMP, 0.5-25 micrograms/kg per min) did not suppress the blood flow response to Ang II. Although at a high dose ANP attenuated the blood flow response to Bay K 8644 (1-4 micrograms), nifedipine pretreatment (20 micrograms/kg plus 1 microgram/kg per min i.v.) did not affect the inhibitory effect of ANP on the NE-induced response. The vaso-inhibitory effects of ANP therefore could not be related exclusively to stimulation of cGMP production or inhibition of voltage-dependent Ca2+ channels.", "contents": "Atrial natriuretic peptide suppresses renal vasoconstriction induced by angiotensin II and norepinephrine in dogs. Atrial natriuretic peptide (ANP, 10 and 50 ng/kg per min), infused into the renal artery, suppressed decreases in renal blood flow induced by intrarenal arterial injection of angiotensin II (Ang II, 25-100 ng) and norepinephrine (NE, 0.25-1 microgram) in anesthetized dogs. Sodium nitroprusside (SNP, 0.1-5.0 micrograms/kg per min) slightly attenuated the blood flow response to Ang II but not the response to NE. 8-Bromo cyclic GMP (8bcGMP, 0.5-25 micrograms/kg per min) did not suppress the blood flow response to Ang II. Although at a high dose ANP attenuated the blood flow response to Bay K 8644 (1-4 micrograms), nifedipine pretreatment (20 micrograms/kg plus 1 microgram/kg per min i.v.) did not affect the inhibitory effect of ANP on the NE-induced response. The vaso-inhibitory effects of ANP therefore could not be related exclusively to stimulation of cGMP production or inhibition of voltage-dependent Ca2+ channels."} {"id": "PMID:1280594", "title": "Effects of FR 113680 and FK 224, novel tachykinin receptor antagonists, on cigarette smoke-induced rat tracheal plasma extravasation.", "content": "We examined the effects of novel tachykinin antagonists, FR 113680 (N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-phenylmethyl-L-phenylalaninamide) and FK 224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N[3-(2-phenthylpheny l) - propionyl]-L-threonyl]-tyrosyl]-L-leucynyl]-D-phenylalanyl]-L-allo - threonyl]-L-asparaginyl]-L-serine nu-lactone) on rat tracheal plasma extravasation induced by cigarette smoke. Intravenous injection of FK 224 (0.032-3.2 mg kg-1) inhibited rat tracheal plasma extravasation induced by cigarette smoke and capsaicin. FR 113680 (32 mg kg-1 i.v.) also significantly inhibited cigarette smoke-induced plasma extravasation, whereas D-chlorpheniramine maleate, FPL 55712, atropine sulfate and indomethacin had no effect. Tracheal plasma extravasation induced by substance P (SP) and neurokinin A (NKA), but not histamine, was also reduced by intravenous administration of FR 113680 and FK 224. These findings suggest that cigarette smoke stimulates primary afferent sensory nerves, releases tachykinins and evokes plasma extravasation in rat trachea.", "contents": "Effects of FR 113680 and FK 224, novel tachykinin receptor antagonists, on cigarette smoke-induced rat tracheal plasma extravasation. We examined the effects of novel tachykinin antagonists, FR 113680 (N alpha-[N alpha-(N alpha-acetyl-L-threonyl)-N1-formyl-D-tryptophyl]-N- methyl-N-phenylmethyl-L-phenylalaninamide) and FK 224 (N-[N2-[N-[N-[N-[2,3-didehydro-N-methyl-N-[N[3-(2-phenthylpheny l) - propionyl]-L-threonyl]-tyrosyl]-L-leucynyl]-D-phenylalanyl]-L-allo - threonyl]-L-asparaginyl]-L-serine nu-lactone) on rat tracheal plasma extravasation induced by cigarette smoke. Intravenous injection of FK 224 (0.032-3.2 mg kg-1) inhibited rat tracheal plasma extravasation induced by cigarette smoke and capsaicin. FR 113680 (32 mg kg-1 i.v.) also significantly inhibited cigarette smoke-induced plasma extravasation, whereas D-chlorpheniramine maleate, FPL 55712, atropine sulfate and indomethacin had no effect. Tracheal plasma extravasation induced by substance P (SP) and neurokinin A (NKA), but not histamine, was also reduced by intravenous administration of FR 113680 and FK 224. These findings suggest that cigarette smoke stimulates primary afferent sensory nerves, releases tachykinins and evokes plasma extravasation in rat trachea."} {"id": "PMID:1280595", "title": "Further evidence from an elastic artery that angiotensin II amplifies noradrenaline-induced contraction through activation of protein kinase C.", "content": "Angiotensin II (AII, 0.1 nM) increased concentration dependently the sensitivity of rabbit aortic rings to low concentrations of noradrenaline. This was not associated with increases in noradrenaline-induced 45Ca2+ uptake or efflux and was prevented by the protein kinase C (PKC) inhibitors staurosporine (0.01 microM) and calphostin C (0.1 microM). Pretreatment of the rings with PMA (phorbol-12-myristate-13-acetate, 0.1 and 1 microM, 24 h at 4 degrees C) abolished the potentiation phenomenon. We conclude that AII potentiation of noradrenaline-induced vascular tone may be due to a PKC-mediated increase in intracellular sensitivity of the contractile apparatus to Ca2+.", "contents": "Further evidence from an elastic artery that angiotensin II amplifies noradrenaline-induced contraction through activation of protein kinase C. Angiotensin II (AII, 0.1 nM) increased concentration dependently the sensitivity of rabbit aortic rings to low concentrations of noradrenaline. This was not associated with increases in noradrenaline-induced 45Ca2+ uptake or efflux and was prevented by the protein kinase C (PKC) inhibitors staurosporine (0.01 microM) and calphostin C (0.1 microM). Pretreatment of the rings with PMA (phorbol-12-myristate-13-acetate, 0.1 and 1 microM, 24 h at 4 degrees C) abolished the potentiation phenomenon. We conclude that AII potentiation of noradrenaline-induced vascular tone may be due to a PKC-mediated increase in intracellular sensitivity of the contractile apparatus to Ca2+."} {"id": "PMID:1280596", "title": "Modification of alpha-adrenoceptor-mediated pressor responses by NG-nitro-L-arginine methyl ester and vasopressin in endotoxin-treated pithed rats.", "content": "Pithed rats were used to compare the abilities of vasopressin and NG-nitro-L-arginine methyl ester (L-NAME) to prevent the early (1 h after starting an endotoxin infusion) E. coli endotoxin-induced impairment of pressor responsiveness to noradrenaline, cirazoline, BHT 933 and to sympathetic stimulation (T8). L-NAME increased arterial blood pressure and augmented pressor responses to noradrenaline and to sympathetic nerve stimulation to a similar degree in control and endotoxin-treated rats. The response to the alpha 1-adrenoceptor agonist cirazoline was augmented by L-NAME in endotoxin-treated rats only, whereas the response to the alpha 2-adrenoceptor agonist BHT 933 was unaffected. Vasopressin (0.64 I.U. kg-1 h-1) prevented the hypotension that resulted from endotoxin administration and produced a similar increase in blood pressure to that produced by L-NAME. This dose of vasopressin also augmented pressor responses to noradrenaline and sympathetic nerve stimulation similarly in both control and endotoxin-treated rats. Sodium nitroprusside, in a dose that mimicked the degree of hypotension caused by endotoxin, also impaired pressor responsiveness to cirazoline; this impairment was prevented by co-infusion of vasopressin. Thus the effects of L-NAME in preventing the early phase of endotoxin-induced impairment of vascular responsiveness may be related to its hypertensive properties, due to inhibition of the constitutive form of nitric oxide synthase, rather than inhibition of endotoxin-induced nitric oxide synthase. These data suggest that early endotoxin-induced impairment of vascular reactivity probably involves factors other than nitric oxide. The well documented effect of endotoxin in inducing nitric oxide synthase probably explains the later, more sustained loss of vascular responsiveness.", "contents": "Modification of alpha-adrenoceptor-mediated pressor responses by NG-nitro-L-arginine methyl ester and vasopressin in endotoxin-treated pithed rats. Pithed rats were used to compare the abilities of vasopressin and NG-nitro-L-arginine methyl ester (L-NAME) to prevent the early (1 h after starting an endotoxin infusion) E. coli endotoxin-induced impairment of pressor responsiveness to noradrenaline, cirazoline, BHT 933 and to sympathetic stimulation (T8). L-NAME increased arterial blood pressure and augmented pressor responses to noradrenaline and to sympathetic nerve stimulation to a similar degree in control and endotoxin-treated rats. The response to the alpha 1-adrenoceptor agonist cirazoline was augmented by L-NAME in endotoxin-treated rats only, whereas the response to the alpha 2-adrenoceptor agonist BHT 933 was unaffected. Vasopressin (0.64 I.U. kg-1 h-1) prevented the hypotension that resulted from endotoxin administration and produced a similar increase in blood pressure to that produced by L-NAME. This dose of vasopressin also augmented pressor responses to noradrenaline and sympathetic nerve stimulation similarly in both control and endotoxin-treated rats. Sodium nitroprusside, in a dose that mimicked the degree of hypotension caused by endotoxin, also impaired pressor responsiveness to cirazoline; this impairment was prevented by co-infusion of vasopressin. Thus the effects of L-NAME in preventing the early phase of endotoxin-induced impairment of vascular responsiveness may be related to its hypertensive properties, due to inhibition of the constitutive form of nitric oxide synthase, rather than inhibition of endotoxin-induced nitric oxide synthase. These data suggest that early endotoxin-induced impairment of vascular reactivity probably involves factors other than nitric oxide. The well documented effect of endotoxin in inducing nitric oxide synthase probably explains the later, more sustained loss of vascular responsiveness."} {"id": "PMID:1280597", "title": "Synergism between interleukin-1 beta and interferon-gamma, an inducer of nitric oxide synthase, in rat lung fibroblasts.", "content": "An L-arginine-dependent pathway, by which L-arginine is metabolised to citrulline and nitrogen oxides, has been recently identified in some cell types. In cultured rat lung fibroblasts the presence of L-arginine was necessary for the production of nitrite to be induced by rat recombinant interferon-gamma and synergistically enhanced by lipopolysaccharide and interleukin-1 beta. Lipopolysaccharide and interleukin-1 beta did not induce nitrite biosynthesis by themselves. Biosynthesis was apparently dependent on tetrahydrobiopterin, since it could be blocked by diaminohydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis. Dexamethasone blocked nitrite production by a receptor-mediated mechanism. These data indicate that rat lung fibroblasts express an L-arginine-dependent nitric oxide synthase which can be induced by some mediators of inflammation.", "contents": "Synergism between interleukin-1 beta and interferon-gamma, an inducer of nitric oxide synthase, in rat lung fibroblasts. An L-arginine-dependent pathway, by which L-arginine is metabolised to citrulline and nitrogen oxides, has been recently identified in some cell types. In cultured rat lung fibroblasts the presence of L-arginine was necessary for the production of nitrite to be induced by rat recombinant interferon-gamma and synergistically enhanced by lipopolysaccharide and interleukin-1 beta. Lipopolysaccharide and interleukin-1 beta did not induce nitrite biosynthesis by themselves. Biosynthesis was apparently dependent on tetrahydrobiopterin, since it could be blocked by diaminohydroxypyrimidine, an inhibitor of tetrahydrobiopterin synthesis. Dexamethasone blocked nitrite production by a receptor-mediated mechanism. These data indicate that rat lung fibroblasts express an L-arginine-dependent nitric oxide synthase which can be induced by some mediators of inflammation."} {"id": "PMID:1280598", "title": "Glibenclamide and L-NG-nitro-arginine methyl ester modulate the ocular and hypotensive effects of calcitonin gene-related peptide.", "content": "Calcitonin gene-related peptide (CGRP) given i.v. to rabbits induced hypotension and a breakdown of the blood-aqueous barrier. Glibenclamide, a blocker of ATP-sensitive K+ (K+ATP) channels antagonized both these effects. The K+ATP channel opener diazoxide reduced blood pressure but did not damage the blood-aqueous barrier. Inhibition of nitric oxide synthase antagonized the effects of CGRP on the blood-aqueous barrier but did not attenuate the hypotensive response. The results suggest that vasodilatation induced by the opening of K+ATP channels is a prerequisite for the effect of CGRP on the blood-aqueous barrier.", "contents": "Glibenclamide and L-NG-nitro-arginine methyl ester modulate the ocular and hypotensive effects of calcitonin gene-related peptide. Calcitonin gene-related peptide (CGRP) given i.v. to rabbits induced hypotension and a breakdown of the blood-aqueous barrier. Glibenclamide, a blocker of ATP-sensitive K+ (K+ATP) channels antagonized both these effects. The K+ATP channel opener diazoxide reduced blood pressure but did not damage the blood-aqueous barrier. Inhibition of nitric oxide synthase antagonized the effects of CGRP on the blood-aqueous barrier but did not attenuate the hypotensive response. The results suggest that vasodilatation induced by the opening of K+ATP channels is a prerequisite for the effect of CGRP on the blood-aqueous barrier."} {"id": "PMID:1280599", "title": "Effect of TGF beta on liver genes expression. Antagonistic effect of TGF beta on IL-6-stimulated genes in Hep 3B cells.", "content": "The effect of transforming growth factor beta (TGF beta) on the expression of a group of liver genes has been investigated in the hepatoma cell line Hep 3B. TGF beta induces a decrease of the basal level of apolipoprotein A-II (ApoA-II), retinol binding protein (RBP) and alpha-fetoprotein (alpha Fp). Furthermore, TGF beta efficiently antagonizes the IL-6-induction of hemopexin (Hpx) and haptoglobin (Hp) and alpha 1-acid glycoprotein (AGP). These effects of TGF beta are apparently mediated by post-transcriptional mechanism(s). These findings, together with previously reported data on the inhibitory effect of TGF beta on acute phase genes (e.g. ApoA-I and albumin), suggest a role for TGF beta in the regulation of expression of liver genes.", "contents": "Effect of TGF beta on liver genes expression. Antagonistic effect of TGF beta on IL-6-stimulated genes in Hep 3B cells. The effect of transforming growth factor beta (TGF beta) on the expression of a group of liver genes has been investigated in the hepatoma cell line Hep 3B. TGF beta induces a decrease of the basal level of apolipoprotein A-II (ApoA-II), retinol binding protein (RBP) and alpha-fetoprotein (alpha Fp). Furthermore, TGF beta efficiently antagonizes the IL-6-induction of hemopexin (Hpx) and haptoglobin (Hp) and alpha 1-acid glycoprotein (AGP). These effects of TGF beta are apparently mediated by post-transcriptional mechanism(s). These findings, together with previously reported data on the inhibitory effect of TGF beta on acute phase genes (e.g. ApoA-I and albumin), suggest a role for TGF beta in the regulation of expression of liver genes."} {"id": "PMID:1280600", "title": "Biochemical characterization of the p51 sub-unit of human immunodeficiency virus reverse transcriptase in homo- and heterodimeric recombinant forms of the enzyme.", "content": "The biochemical properties of the p51 subunit of HIV-1 reverse transcriptase (RT) were studied in order to understand its role in the heterodimeric form p66/p51 found in virions. A recombinant form of RT, p51/p51, expressed in yeast, was purified and characterized. The enzyme was affinity labeled using a 5' modified oligonucleotide primer, covalently linked, that was further elongated in the presence of a radioactive dNTP precursor. We found that the p51 subunit was labeled in the p51/p51 form, thus reflecting its activity, while this subunit was catalytically silent in the heterodimer, since only the p66 subunit was labeled in the latter recombinant form. Processivity studies showed long-sized products synthesized by p51/p51, as in the case of the other RT forms. The effect of primer tRNA(Lys) on the p51/p51 activity showed a strong inhibitory effect in the absence of KCl, similar to that observed with the p66/p51 form, while the same p51/p51 enzyme was strongly stimulated by tRNA(Lys), like RT p66/p66, when KCl was present in the incubation mixture.", "contents": "Biochemical characterization of the p51 sub-unit of human immunodeficiency virus reverse transcriptase in homo- and heterodimeric recombinant forms of the enzyme. The biochemical properties of the p51 subunit of HIV-1 reverse transcriptase (RT) were studied in order to understand its role in the heterodimeric form p66/p51 found in virions. A recombinant form of RT, p51/p51, expressed in yeast, was purified and characterized. The enzyme was affinity labeled using a 5' modified oligonucleotide primer, covalently linked, that was further elongated in the presence of a radioactive dNTP precursor. We found that the p51 subunit was labeled in the p51/p51 form, thus reflecting its activity, while this subunit was catalytically silent in the heterodimer, since only the p66 subunit was labeled in the latter recombinant form. Processivity studies showed long-sized products synthesized by p51/p51, as in the case of the other RT forms. The effect of primer tRNA(Lys) on the p51/p51 activity showed a strong inhibitory effect in the absence of KCl, similar to that observed with the p66/p51 form, while the same p51/p51 enzyme was strongly stimulated by tRNA(Lys), like RT p66/p66, when KCl was present in the incubation mixture."} {"id": "PMID:1280601", "title": "Changes in chromatin structure due to hypomethylation induced with 5-azacytidine or DL-ethionine.", "content": "Changes in chromatin structure of the HRS60 family of repetitive sequences in tobacco DNA were studied after hypomethylation induced with 5-azacytidine or DL-ethionine. The TaqI site in the HRS60 units lies in nucleosomal core regions and its cleavage is enhanced in the hypomethylated chromatin. In contrast, the cleavage of the Sau3AI site located in linker DNA does not depend on the level of methylation of DNA.", "contents": "Changes in chromatin structure due to hypomethylation induced with 5-azacytidine or DL-ethionine. Changes in chromatin structure of the HRS60 family of repetitive sequences in tobacco DNA were studied after hypomethylation induced with 5-azacytidine or DL-ethionine. The TaqI site in the HRS60 units lies in nucleosomal core regions and its cleavage is enhanced in the hypomethylated chromatin. In contrast, the cleavage of the Sau3AI site located in linker DNA does not depend on the level of methylation of DNA."} {"id": "PMID:1280602", "title": "The amphicrine pancreatic cell line, AR42J, secretes GABA and amylase by separate regulated pathways.", "content": "Treatment of AR42J cells with dexamethasone leads to an enhanced formation of amylase-containing granules and facilitates their regulated secretion. Besides the exocrine properties, AR42J cells possess a specific uptake system for [3H]GABA. The stored GABA can be released upon potassium depolarisation in a Ca(2+)-dependent manner. After treatment with dexamethasone, potassium depolarisation fails to release GABA, but instead causes a Ca(2+)-dependent secretion of amylase. Since vesicles similar to small synaptic vesicles of neurons have been identified in AR42J cells, we suggest that the regulated GABA release is mediated by this vesicle type. It is tentatively speculated that other epithelial cells, which also contain small synaptic vesicles and amino acid neurotransmitters, may release them in a similar fashion.", "contents": "The amphicrine pancreatic cell line, AR42J, secretes GABA and amylase by separate regulated pathways. Treatment of AR42J cells with dexamethasone leads to an enhanced formation of amylase-containing granules and facilitates their regulated secretion. Besides the exocrine properties, AR42J cells possess a specific uptake system for [3H]GABA. The stored GABA can be released upon potassium depolarisation in a Ca(2+)-dependent manner. After treatment with dexamethasone, potassium depolarisation fails to release GABA, but instead causes a Ca(2+)-dependent secretion of amylase. Since vesicles similar to small synaptic vesicles of neurons have been identified in AR42J cells, we suggest that the regulated GABA release is mediated by this vesicle type. It is tentatively speculated that other epithelial cells, which also contain small synaptic vesicles and amino acid neurotransmitters, may release them in a similar fashion."} {"id": "PMID:1280603", "title": "Inhibition of actin-activated myosin Mg(2+)-ATPase in smooth muscle by ruthenium red.", "content": "Ruthenium red was found to inhibit actin-activated myosin Mg(2+)-ATPase in smooth muscle and to bind to myosin heavy chain, but not to F-actin. The inhibition by Ruthenium red of actin-activated Mg(2+)-ATPase was of the competitive type with respect to actin (Ki 4.4 microM) and of the non-competitive type with respect to ATP (Ki 6.6 microM). However, Ruthenium red scarcely dissociated the acto-heavy meromyosin complex during the ATPase reaction. These results suggest that Ruthenium red interacts directly with the binding site for F-actin on the myosin heavy chain. This site is considered to be necessary not for maintaining the binding affinity of myosin for F-actin, but for activation of the Mg(2+)-ATPase.", "contents": "Inhibition of actin-activated myosin Mg(2+)-ATPase in smooth muscle by ruthenium red. Ruthenium red was found to inhibit actin-activated myosin Mg(2+)-ATPase in smooth muscle and to bind to myosin heavy chain, but not to F-actin. The inhibition by Ruthenium red of actin-activated Mg(2+)-ATPase was of the competitive type with respect to actin (Ki 4.4 microM) and of the non-competitive type with respect to ATP (Ki 6.6 microM). However, Ruthenium red scarcely dissociated the acto-heavy meromyosin complex during the ATPase reaction. These results suggest that Ruthenium red interacts directly with the binding site for F-actin on the myosin heavy chain. This site is considered to be necessary not for maintaining the binding affinity of myosin for F-actin, but for activation of the Mg(2+)-ATPase."} {"id": "PMID:1280605", "title": "Altering the course of proliferative nephritides: the challenge of the 1990s.", "content": "There is considerable evidence based on experimental pathology that heparin/heparinoids will benefit the course of the various forms of human proliferative nephritis. An alternative to heparin may be pentosan polysulphate. Another possibility is the infusion of prostaglandin E1 because of its anti-inflammatory and potentially antiproliferative actions. Both these approaches mimic natural pathophysiological control mechanisms.", "contents": "Altering the course of proliferative nephritides: the challenge of the 1990s. There is considerable evidence based on experimental pathology that heparin/heparinoids will benefit the course of the various forms of human proliferative nephritis. An alternative to heparin may be pentosan polysulphate. Another possibility is the infusion of prostaglandin E1 because of its anti-inflammatory and potentially antiproliferative actions. Both these approaches mimic natural pathophysiological control mechanisms."} {"id": "PMID:1280606", "title": "Effects of biological response modifiers with different modes of action used separately and together on immune responses in mice with syngeneic tumours.", "content": "The effect of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of the Basidiomycetes Coriolus versicolor on activities involved in the host defence mechanism of C57BL/6 mice bearing adenocarcinoma 755 was compared with that of live bacille Calmette-Gu\u00e9rin (BCG). Delayed footpad reaction, the activity of splenic natural killer cells and interferon production induced by concanavalin A in splenic cells of healthy mice were little affected by PSK, but in mice bearing tumours PSK prevented the tumour-induced reduction in these activities. Live BCG augmented these activities in healthy mice but had little effect on the reduction of activities induced by a tumour. The immunosuppressive activity of the serum of tumour-bearing mice was reduced by PSK administration; live BCG did not have this effect. The combined use of live BCG and PSK improved these activities in the host, with synergistic increases in the antitumour effect. These results suggest that the combined use of live BCG and PSK, which have different modes of action, may be useful in the treatment of cancer.", "contents": "Effects of biological response modifiers with different modes of action used separately and together on immune responses in mice with syngeneic tumours. The effect of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of the Basidiomycetes Coriolus versicolor on activities involved in the host defence mechanism of C57BL/6 mice bearing adenocarcinoma 755 was compared with that of live bacille Calmette-Gu\u00e9rin (BCG). Delayed footpad reaction, the activity of splenic natural killer cells and interferon production induced by concanavalin A in splenic cells of healthy mice were little affected by PSK, but in mice bearing tumours PSK prevented the tumour-induced reduction in these activities. Live BCG augmented these activities in healthy mice but had little effect on the reduction of activities induced by a tumour. The immunosuppressive activity of the serum of tumour-bearing mice was reduced by PSK administration; live BCG did not have this effect. The combined use of live BCG and PSK improved these activities in the host, with synergistic increases in the antitumour effect. These results suggest that the combined use of live BCG and PSK, which have different modes of action, may be useful in the treatment of cancer."} {"id": "PMID:1280607", "title": "Modulation of embryonic and muscle-specific enolase gene products in the developing mouse hindlimb.", "content": "During striated muscle development, the glycolytic enzyme enolase (EC 4.2.1.11) undergoes an isozymic transition, from the embryonic alpha alpha form towards the muscle-specific forms alpha beta and beta beta. The regulation of this transition was analyzed in mouse hindlimb muscles from embryonic day 15 (E15) to the adult stage. The quantitative modulations of the levels of the transcripts and subunits of alpha and beta enolase genes were determined. The absolute amounts of alpha and beta enolase mRNAs were estimated using in vitro synthesized transcripts as calibration standards, thus allowing an evaluation of their relative contribution at each stage examined. The muscle-specific beta enolase mRNA is already present at E15. Its level then increases and, from E17, this transcript becomes predominant. This accumulation is biphasic: a steep prenatal rise, corresponding to a net increase per fiber, accompanies the formation of secondary myofibers and the development of innervation; a second rise, beginning at postnatal day 5, is temporally correlated with the definitive specialization of the myofibers. Most of the decrease in alpha mRNA level occurs postnatally. No temporal or quantitative correlation between the up-regulation of beta mRNA and the down-regulation of alpha mRNA levels is observed throughout hindlimb muscle development. Quantitative immunoblotting analyses carried out in parallel show that the enolase isozymic transition is mainly controlled at the mRNA level.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Modulation of embryonic and muscle-specific enolase gene products in the developing mouse hindlimb. During striated muscle development, the glycolytic enzyme enolase (EC 4.2.1.11) undergoes an isozymic transition, from the embryonic alpha alpha form towards the muscle-specific forms alpha beta and beta beta. The regulation of this transition was analyzed in mouse hindlimb muscles from embryonic day 15 (E15) to the adult stage. The quantitative modulations of the levels of the transcripts and subunits of alpha and beta enolase genes were determined. The absolute amounts of alpha and beta enolase mRNAs were estimated using in vitro synthesized transcripts as calibration standards, thus allowing an evaluation of their relative contribution at each stage examined. The muscle-specific beta enolase mRNA is already present at E15. Its level then increases and, from E17, this transcript becomes predominant. This accumulation is biphasic: a steep prenatal rise, corresponding to a net increase per fiber, accompanies the formation of secondary myofibers and the development of innervation; a second rise, beginning at postnatal day 5, is temporally correlated with the definitive specialization of the myofibers. Most of the decrease in alpha mRNA level occurs postnatally. No temporal or quantitative correlation between the up-regulation of beta mRNA and the down-regulation of alpha mRNA levels is observed throughout hindlimb muscle development. Quantitative immunoblotting analyses carried out in parallel show that the enolase isozymic transition is mainly controlled at the mRNA level.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280608", "title": "Widespread differentiation stage-specific expression of the gene encoding phosphoprotein p19 (metablastin) in mammalian cells.", "content": "p19 is a highly conserved 19 kD cytosolic protein that undergoes phosphorylation in response to diverse extracellular factors in mammalian cells. Its expression is abundant in brain and testis and is developmentally regulated. To gain insights regarding its function, we analyzed the expression of p19 mRNA in a variety of cell types during induction of differentiation. Murine erythroleukemia cells showed a moderate increase followed by a marked decrease in the abundance of p19 mRNA during induction of differentiation. In murine C2 myoblasts and primary fetal rat osteoblasts, p19 mRNA was abundant in replicating cells and decreased to undetectable levels during differentiation. In resting human peripheral blood lymphocytes, p19 mRNA was virtually undetectable but was strongly induced during blast transformation of both B and T cells. In rat liver, p19 mRNA was abundant on embryonic day 17 and decreased during early postnatal development. Upon fractionation of adult rat liver cells by centrifugal elutriation, p19 mRNA was not detected in hepatocytes while a low level was observed in a fraction enriched in non-parenchymal epithelial cells. CCl4-induced liver regeneration resulted in induction of p19 mRNA in hepatocytes. Primary cultures of embryonic and neonatal rat brain were analyzed by indirect immunofluorescence using co-staining with stage-specific markers. p19 expression was restricted to immature neurons and oligodendrocyte precursors. In contrast to the other cell types examined, the neuronal and glial precursors that express p19 were shown, using BrdU labeling, to be postmitotic both in primary culture and in vivo. The data demonstrate widespread, stage-specific expression of p19 and suggest that the protein exerts a general, lineage-independent function during induction of differentiation of mammalian cells. In view of the available evidence on the stimulation of serine phosphorylation of p19 by several growth factors, our working hypothesis is that phosphorylation of p19 may be involved in the mechanism by which growth factors control cell differentiation.", "contents": "Widespread differentiation stage-specific expression of the gene encoding phosphoprotein p19 (metablastin) in mammalian cells. p19 is a highly conserved 19 kD cytosolic protein that undergoes phosphorylation in response to diverse extracellular factors in mammalian cells. Its expression is abundant in brain and testis and is developmentally regulated. To gain insights regarding its function, we analyzed the expression of p19 mRNA in a variety of cell types during induction of differentiation. Murine erythroleukemia cells showed a moderate increase followed by a marked decrease in the abundance of p19 mRNA during induction of differentiation. In murine C2 myoblasts and primary fetal rat osteoblasts, p19 mRNA was abundant in replicating cells and decreased to undetectable levels during differentiation. In resting human peripheral blood lymphocytes, p19 mRNA was virtually undetectable but was strongly induced during blast transformation of both B and T cells. In rat liver, p19 mRNA was abundant on embryonic day 17 and decreased during early postnatal development. Upon fractionation of adult rat liver cells by centrifugal elutriation, p19 mRNA was not detected in hepatocytes while a low level was observed in a fraction enriched in non-parenchymal epithelial cells. CCl4-induced liver regeneration resulted in induction of p19 mRNA in hepatocytes. Primary cultures of embryonic and neonatal rat brain were analyzed by indirect immunofluorescence using co-staining with stage-specific markers. p19 expression was restricted to immature neurons and oligodendrocyte precursors. In contrast to the other cell types examined, the neuronal and glial precursors that express p19 were shown, using BrdU labeling, to be postmitotic both in primary culture and in vivo. The data demonstrate widespread, stage-specific expression of p19 and suggest that the protein exerts a general, lineage-independent function during induction of differentiation of mammalian cells. In view of the available evidence on the stimulation of serine phosphorylation of p19 by several growth factors, our working hypothesis is that phosphorylation of p19 may be involved in the mechanism by which growth factors control cell differentiation."} {"id": "PMID:1280609", "title": "Characterization of the Salmonella typhimurium phoE gene and development of Salmonella-specific DNA probes.", "content": "In Escherichia coli K-12, the phoE gene, encoding a phosphate-limitation-inducible outer membrane pore protein (PhoE), is closely linked to the genes proA and proB. When the corresponding fragment of the Salmonella typhimurium chromosome was transferred to E. coli K-12 using an RP4::miniMu plasmid, pULB113, no production of S. typhimurium PhoE could be detected. Nevertheless, DNA hybridization studies revealed that the corresponding plasmid did contain S. typhimurium phoE. Production of S. typhimurium PhoE in E. coli was detected only after subcloning the gene in a multicopy vector. Nucleotide (nt) sequence analysis showed extensive homology of S. typhimurium phoE to the E. coli gene and suggested possible explanations for the low expression of S. typhimurium phoE in E. coli. In addition, the sequence information was used to develop Salmonella-specific DNA probes. Two oligodeoxyribonucleotides were synthesized based on nt sequences encoding the fifth and eighth cell-surface-exposed regions of PhoE. When used in polymerase chain reactions, these probes turned out to be specific, i.e., no crossreactions occurred with the non-Salmonella strains, whereas 132 out of 133 tested Salmonella strains were recognized.", "contents": "Characterization of the Salmonella typhimurium phoE gene and development of Salmonella-specific DNA probes. In Escherichia coli K-12, the phoE gene, encoding a phosphate-limitation-inducible outer membrane pore protein (PhoE), is closely linked to the genes proA and proB. When the corresponding fragment of the Salmonella typhimurium chromosome was transferred to E. coli K-12 using an RP4::miniMu plasmid, pULB113, no production of S. typhimurium PhoE could be detected. Nevertheless, DNA hybridization studies revealed that the corresponding plasmid did contain S. typhimurium phoE. Production of S. typhimurium PhoE in E. coli was detected only after subcloning the gene in a multicopy vector. Nucleotide (nt) sequence analysis showed extensive homology of S. typhimurium phoE to the E. coli gene and suggested possible explanations for the low expression of S. typhimurium phoE in E. coli. In addition, the sequence information was used to develop Salmonella-specific DNA probes. Two oligodeoxyribonucleotides were synthesized based on nt sequences encoding the fifth and eighth cell-surface-exposed regions of PhoE. When used in polymerase chain reactions, these probes turned out to be specific, i.e., no crossreactions occurred with the non-Salmonella strains, whereas 132 out of 133 tested Salmonella strains were recognized."} {"id": "PMID:1280610", "title": "Coeliac disease: characterisation of monoclonal antibodies raised against a synthetic peptide corresponding to amino acid residues 206-217 of A-gliadin.", "content": "A dodecapeptide of A-gliadin, which shares amino acid homologies with the E1b protein of adenovirus 12, was used to produce murine monoclonal antibodies. Five monoclonal antibodies were produced and were screened by enzyme linked immunosorbant assay, immunodot assay, and immunoblotting. The antibodies were tested against whole wheat gliadin and its alpha, beta, gamma, and omega subfractions, and the prolamins of rye, barley, oats, maize, millet, rice, and sorghum. Four of the five antibodies cross reacted with one or more of the coeliac non-toxic cereals--maize, millet, sorghum, and rice. The monoclonal antibody that did not cross react with these non-toxic cereals, did not recognize Frazer's fraction III, a peptic-tryptic digest of wheat gluten which is known to be toxic. The results suggest that the A-gliadin dodecapeptide shares a region of homology with cereals that do not exacerbate coeliac disease. This study does not support the hypothesis that prior infection with adenovirus 12 is a precipitating factor in coeliac disease.", "contents": "Coeliac disease: characterisation of monoclonal antibodies raised against a synthetic peptide corresponding to amino acid residues 206-217 of A-gliadin. A dodecapeptide of A-gliadin, which shares amino acid homologies with the E1b protein of adenovirus 12, was used to produce murine monoclonal antibodies. Five monoclonal antibodies were produced and were screened by enzyme linked immunosorbant assay, immunodot assay, and immunoblotting. The antibodies were tested against whole wheat gliadin and its alpha, beta, gamma, and omega subfractions, and the prolamins of rye, barley, oats, maize, millet, rice, and sorghum. Four of the five antibodies cross reacted with one or more of the coeliac non-toxic cereals--maize, millet, sorghum, and rice. The monoclonal antibody that did not cross react with these non-toxic cereals, did not recognize Frazer's fraction III, a peptic-tryptic digest of wheat gluten which is known to be toxic. The results suggest that the A-gliadin dodecapeptide shares a region of homology with cereals that do not exacerbate coeliac disease. This study does not support the hypothesis that prior infection with adenovirus 12 is a precipitating factor in coeliac disease."} {"id": "PMID:1280611", "title": "Importance of endogenous prostaglandins for the toxicity of cyclosporin A to rat endocrine and exocrine pancreas?", "content": "Previous work has shown that cyclosporin A is toxic to the endocrine and exocrine pancreas. The aim of this study was to examine whether endogenous eicosanoids play a role in controlling cyclosporin A induced toxicity. Rats were treated for eight days with indomethacin (2 mg/kg, twice daily) in addition to cyclosporin A (5 or 10 mg/kg daily). Effects of drug treatments on exocrine (as assessed by amylase and protein secretion into the pancreatic juice) and endocrine (as assessed by the glucose dependent insulin release) pancreatic functions, and pancreatic formation of prostaglandins and thromboxane were evaluated. Treatment with cyclosporin A in the doses used did not inhibit eicosanoid formation by the pancreatic tissue ex vivo. Indomethacin caused significant inhibition of pancreatic formation of prostaglandin E2, 6k prostaglandin F1 alpha and thromboxane B2. Combined treatment with indomethacin and cyclosporin A (5 or 10 mg/kg) augmented cyclosporin A induced pancreatic toxicity with further impairment of insulin release, amylase secretion, and pancreatic juice protein content, but did not result in more pronounced inhibition of pancreatic eicosanoid formation. The increased toxicity of the combined treatment was, however, associated with raised cyclosporin A whole blood concentrations. The data suggest that the potentiation of pancreatic toxicity of cyclosporin A observed during coadministration of indomethacin is not the result of suppression of endogenous pancreatic eicosanoid biosynthesis, but more likely results from altered cyclosporin A pharmacokinetic which may be caused by an interference of indomethacin with the hepatic cytochrome P-450 dependent monooxygenase involved in cyclosporin A metabolism. The possibility that coadministration of non-steroidal antiinflammatory drugs aggravates toxic effects in cyclosporin A treated patients should be considered.", "contents": "Importance of endogenous prostaglandins for the toxicity of cyclosporin A to rat endocrine and exocrine pancreas? Previous work has shown that cyclosporin A is toxic to the endocrine and exocrine pancreas. The aim of this study was to examine whether endogenous eicosanoids play a role in controlling cyclosporin A induced toxicity. Rats were treated for eight days with indomethacin (2 mg/kg, twice daily) in addition to cyclosporin A (5 or 10 mg/kg daily). Effects of drug treatments on exocrine (as assessed by amylase and protein secretion into the pancreatic juice) and endocrine (as assessed by the glucose dependent insulin release) pancreatic functions, and pancreatic formation of prostaglandins and thromboxane were evaluated. Treatment with cyclosporin A in the doses used did not inhibit eicosanoid formation by the pancreatic tissue ex vivo. Indomethacin caused significant inhibition of pancreatic formation of prostaglandin E2, 6k prostaglandin F1 alpha and thromboxane B2. Combined treatment with indomethacin and cyclosporin A (5 or 10 mg/kg) augmented cyclosporin A induced pancreatic toxicity with further impairment of insulin release, amylase secretion, and pancreatic juice protein content, but did not result in more pronounced inhibition of pancreatic eicosanoid formation. The increased toxicity of the combined treatment was, however, associated with raised cyclosporin A whole blood concentrations. The data suggest that the potentiation of pancreatic toxicity of cyclosporin A observed during coadministration of indomethacin is not the result of suppression of endogenous pancreatic eicosanoid biosynthesis, but more likely results from altered cyclosporin A pharmacokinetic which may be caused by an interference of indomethacin with the hepatic cytochrome P-450 dependent monooxygenase involved in cyclosporin A metabolism. The possibility that coadministration of non-steroidal antiinflammatory drugs aggravates toxic effects in cyclosporin A treated patients should be considered."} {"id": "PMID:1280612", "title": "Stimulatory effect of oCRH on alpha-subunit secretion during petrosal sinus sampling in patients with Cushing's disease.", "content": "During bilateral and simultaneous venous sampling of the inferior petrosal sinuses for preoperative localization of ACTH secreting microadenomas, alpha-subunit levels, in addition to ACTH, were determined in 9 patients with Cushing's disease. The aim of the study was to evaluate the possible occurrence of unilateral increases of alpha-subunit in basal conditions and the alpha-subunit responsiveness to oCRH. All the patients examined showed a central to peripheral and an intersinus gradient of ACTH concentrations before and/or after oCRH stimulation. Seven patients showed a central to peripheral alpha-subunit gradient in basal conditions. Lateralization of alpha-subunit concentrations was recorded in 4 patients in basal conditions (intersinus gradient > or = 1.55) and paralleled the side with the highest ACTH concentrations. After oCRH stimulation all but one patient showed a unilateral alpha-subunit increase in blood from the inferior petrosal sinus with the highest oCRH stimulated ACTH increase. The present data confirm the occurrence of an increase of alpha-subunit concentration in response to nonspecific stimulation with exogenously administered oCRH, concurrent with an ipsilateral increase of ACTH levels. The mechanism underlying this finding is still unclear, although a paracrine effect from the corticotroph tumour on adjacent pituitary tissue seems so far the most likely explanation.", "contents": "Stimulatory effect of oCRH on alpha-subunit secretion during petrosal sinus sampling in patients with Cushing's disease. During bilateral and simultaneous venous sampling of the inferior petrosal sinuses for preoperative localization of ACTH secreting microadenomas, alpha-subunit levels, in addition to ACTH, were determined in 9 patients with Cushing's disease. The aim of the study was to evaluate the possible occurrence of unilateral increases of alpha-subunit in basal conditions and the alpha-subunit responsiveness to oCRH. All the patients examined showed a central to peripheral and an intersinus gradient of ACTH concentrations before and/or after oCRH stimulation. Seven patients showed a central to peripheral alpha-subunit gradient in basal conditions. Lateralization of alpha-subunit concentrations was recorded in 4 patients in basal conditions (intersinus gradient > or = 1.55) and paralleled the side with the highest ACTH concentrations. After oCRH stimulation all but one patient showed a unilateral alpha-subunit increase in blood from the inferior petrosal sinus with the highest oCRH stimulated ACTH increase. The present data confirm the occurrence of an increase of alpha-subunit concentration in response to nonspecific stimulation with exogenously administered oCRH, concurrent with an ipsilateral increase of ACTH levels. The mechanism underlying this finding is still unclear, although a paracrine effect from the corticotroph tumour on adjacent pituitary tissue seems so far the most likely explanation."} {"id": "PMID:1280613", "title": "Insulin-like growth factor binding protein 1 (IGFBP-1) levels in Turner syndrome.", "content": "We tested whether IGFBP-1, a modulator of IGF-I action, would play a role in the pathogenesis of growth failure and metabolic picture of Turner syndrome. Fasting serum levels of IGFBP-1 were assessed in nineteen girls with Turner syndrome (aging 6.5 to 17.2 years) by radioimmunoassay. Our patients showed normal values of IGFBP-1 (mean +/- SD: 68.6 +/- 32.5 micrograms/l, range: 16 to 134 micrograms/l; range for age and pubertal stage-matched normal children: 15 to 180 micrograms/l). IGFBP-1 levels inversely correlated with bone age (p < 0.05), weight (p < 0.001), percentage of ideal body weight (p < 0.002) and body mass index (BMI) (p < 0.001). Our results seem to rule out a role of IGFBP-1 in the pathogenesis of growth failure in Turner syndrome. The close inverse relationship between IGFBP-1 levels and BMI suggests the serum concentrations of IGFBP-1 to be regulated by the nutritional status. Due to IGFBP-1 inhibiting action on IGF biological activity, the reduction of IGFBP-1 levels in overweight subjects might represent a mechanism to enhance the IGF insulin-like activity, thus supplementing the insulin action.", "contents": "Insulin-like growth factor binding protein 1 (IGFBP-1) levels in Turner syndrome. We tested whether IGFBP-1, a modulator of IGF-I action, would play a role in the pathogenesis of growth failure and metabolic picture of Turner syndrome. Fasting serum levels of IGFBP-1 were assessed in nineteen girls with Turner syndrome (aging 6.5 to 17.2 years) by radioimmunoassay. Our patients showed normal values of IGFBP-1 (mean +/- SD: 68.6 +/- 32.5 micrograms/l, range: 16 to 134 micrograms/l; range for age and pubertal stage-matched normal children: 15 to 180 micrograms/l). IGFBP-1 levels inversely correlated with bone age (p < 0.05), weight (p < 0.001), percentage of ideal body weight (p < 0.002) and body mass index (BMI) (p < 0.001). Our results seem to rule out a role of IGFBP-1 in the pathogenesis of growth failure in Turner syndrome. The close inverse relationship between IGFBP-1 levels and BMI suggests the serum concentrations of IGFBP-1 to be regulated by the nutritional status. Due to IGFBP-1 inhibiting action on IGF biological activity, the reduction of IGFBP-1 levels in overweight subjects might represent a mechanism to enhance the IGF insulin-like activity, thus supplementing the insulin action."} {"id": "PMID:1280615", "title": "Intermediate filament expression in mesotheliomas: leiomyoid mesotheliomas are not uncommon.", "content": "In this study we examined intermediate filament expression in 45 formalin-fixed mesotheliomas. Immunostaining for cytokeratin was found in 86%, for vimentin in 71%, and for desmin in 4%; none stained for glial fibrillary acidic protein or neurofilament. The two biphasic mesotheliomas which expressed desmin also expressed smooth muscle actin but were negative for myoglobin. This, together with the ultrastructural findings, was taken as unequivocal evidence of a leiomyoid form of mesothelioma which might easily be confused with leiomyosarcoma. Both of these tumours co-expressed cytokeratin, exemplifying the value of cytokeratin immunostaining in the distinction between mesothelioma and sarcoma. Consistent non-expression of glial fibrillary acidic protein in mesotheliomas may help to distinguish them from nerve sheath tumours.", "contents": "Intermediate filament expression in mesotheliomas: leiomyoid mesotheliomas are not uncommon. In this study we examined intermediate filament expression in 45 formalin-fixed mesotheliomas. Immunostaining for cytokeratin was found in 86%, for vimentin in 71%, and for desmin in 4%; none stained for glial fibrillary acidic protein or neurofilament. The two biphasic mesotheliomas which expressed desmin also expressed smooth muscle actin but were negative for myoglobin. This, together with the ultrastructural findings, was taken as unequivocal evidence of a leiomyoid form of mesothelioma which might easily be confused with leiomyosarcoma. Both of these tumours co-expressed cytokeratin, exemplifying the value of cytokeratin immunostaining in the distinction between mesothelioma and sarcoma. Consistent non-expression of glial fibrillary acidic protein in mesotheliomas may help to distinguish them from nerve sheath tumours."} {"id": "PMID:1280617", "title": "Microwave effects on input resistance and action potential firing of snail neurons.", "content": "Excitable tissues have been reported to respond to weak microwave (MW) fields, possibly by nonlinear perturbation of a cellular process such as ion conduction across membranes. We sought effects of MW (continuous wave, 2.45 GHz, specific absorption rates 12.5 or 125 mW/g) on input resistances and action potential (AP) intervals of neurons in ganglia of snails (Helix aspersa), at 20.9 +/- 0.1 degrees C. At 12.5 mW/g, input resistance did not change during irradiation, but increased (p < 0.05) afterward. At 125 mW/g, input resistance during irradiation was lower than in unirradiated controls. Serial correlograms changed marginally more frequently in MW experiments than in controls, but the changes had no consistent pattern. The AP firing rate was affected by MW, but the direction was not consistent across cells. When AP generation was modeled as being due to a neuronal input current, MW did not affect its mean, standard deviation, or autocorrelation. Unlike MW, temperature changes caused neurons to respond robustly and reversibly. Threshold for changing input resistance was 0.63 degree C. The data suggest that MW may enhance degenerative effects such as metabolic rundown or loss of ion channel patency, but do not indicate a specific mechanism for MW interaction with neurons.", "contents": "Microwave effects on input resistance and action potential firing of snail neurons. Excitable tissues have been reported to respond to weak microwave (MW) fields, possibly by nonlinear perturbation of a cellular process such as ion conduction across membranes. We sought effects of MW (continuous wave, 2.45 GHz, specific absorption rates 12.5 or 125 mW/g) on input resistances and action potential (AP) intervals of neurons in ganglia of snails (Helix aspersa), at 20.9 +/- 0.1 degrees C. At 12.5 mW/g, input resistance did not change during irradiation, but increased (p < 0.05) afterward. At 125 mW/g, input resistance during irradiation was lower than in unirradiated controls. Serial correlograms changed marginally more frequently in MW experiments than in controls, but the changes had no consistent pattern. The AP firing rate was affected by MW, but the direction was not consistent across cells. When AP generation was modeled as being due to a neuronal input current, MW did not affect its mean, standard deviation, or autocorrelation. Unlike MW, temperature changes caused neurons to respond robustly and reversibly. Threshold for changing input resistance was 0.63 degree C. The data suggest that MW may enhance degenerative effects such as metabolic rundown or loss of ion channel patency, but do not indicate a specific mechanism for MW interaction with neurons."} {"id": "PMID:1280619", "title": "Application of BrdU/Hoechst-ethidium bromide two parameter flow cytometry in studying synchronous and non-synchronous mouse cells.", "content": "BrdU/Hoechst-EB bivariate flow cytometry has a wide application in the study of factors controlling cell cycle for asynchronous cells such as embryonic stem cells (ES), and for synchronous cells such as stimulated resting B cells (Bo). The technique allows one to calculate the average cell cycle duration time. ES cells are found to cycle every 8-10 h, and most B cells are 11-12 h, but there is a small subset of B cells with a cycle time of only 6-7 h. Using this technique, we also study the roles of different T lymphocytes on B cell activation when B cells are stimulated with anti-IgM antibodies (commonly used, anti-mu). Exposure to anti-mu recruits small B cells into the cell cycle, but arrests them in the G1 phase of the second cycle. Interleukin (IL) 4 is a costimulator of anti-mu. In addition, IL-4 is an S-phase progression factor. Contrary to that seen when B cells are stimulated by other mitogens, very few cells are in the G2 compartments after anti-mu plus IL-4 stimulation. This phenomenon is reminiscent of embryonic cells. Our findings provide strong evidence to propose that there are two restriction points for B cell activation: at the transition from G0 to G1 and at the transition from G1 to S phase.", "contents": "Application of BrdU/Hoechst-ethidium bromide two parameter flow cytometry in studying synchronous and non-synchronous mouse cells. BrdU/Hoechst-EB bivariate flow cytometry has a wide application in the study of factors controlling cell cycle for asynchronous cells such as embryonic stem cells (ES), and for synchronous cells such as stimulated resting B cells (Bo). The technique allows one to calculate the average cell cycle duration time. ES cells are found to cycle every 8-10 h, and most B cells are 11-12 h, but there is a small subset of B cells with a cycle time of only 6-7 h. Using this technique, we also study the roles of different T lymphocytes on B cell activation when B cells are stimulated with anti-IgM antibodies (commonly used, anti-mu). Exposure to anti-mu recruits small B cells into the cell cycle, but arrests them in the G1 phase of the second cycle. Interleukin (IL) 4 is a costimulator of anti-mu. In addition, IL-4 is an S-phase progression factor. Contrary to that seen when B cells are stimulated by other mitogens, very few cells are in the G2 compartments after anti-mu plus IL-4 stimulation. This phenomenon is reminiscent of embryonic cells. Our findings provide strong evidence to propose that there are two restriction points for B cell activation: at the transition from G0 to G1 and at the transition from G1 to S phase."} {"id": "PMID:1280620", "title": "Properties of soluble CR2 in human serum.", "content": "A soluble form of complement receptor number 2 (sCR2) found in human serum closely resembles that produced in culture by B lymphoblastoid cells. Epitope analysis with a panel of CD21 monoclonal antibodies revealed only minor differences between antigen from the two sources. Purified sCR2 from both sources bound to C3dg prepared from human or mouse serum and to u.v.-inactivated Epstein-Barr virus. SDS-PAGE analysis of culture supernates of B-lymphoid cells labelled by growth in medium containing 35S-methionine revealed a major component of molecular weight approximately 130 kDa and another band at 30 kDa. Incubation with endoglycosidase F reduced the size of the high molecular weight component. Gel filtration of untreated serum or culture supernate revealed that, in its native state, sCR2 behaved as a molecule or complex of apparent molecular weight 320 kDa. Possible explanations are discussed.", "contents": "Properties of soluble CR2 in human serum. A soluble form of complement receptor number 2 (sCR2) found in human serum closely resembles that produced in culture by B lymphoblastoid cells. Epitope analysis with a panel of CD21 monoclonal antibodies revealed only minor differences between antigen from the two sources. Purified sCR2 from both sources bound to C3dg prepared from human or mouse serum and to u.v.-inactivated Epstein-Barr virus. SDS-PAGE analysis of culture supernates of B-lymphoid cells labelled by growth in medium containing 35S-methionine revealed a major component of molecular weight approximately 130 kDa and another band at 30 kDa. Incubation with endoglycosidase F reduced the size of the high molecular weight component. Gel filtration of untreated serum or culture supernate revealed that, in its native state, sCR2 behaved as a molecule or complex of apparent molecular weight 320 kDa. Possible explanations are discussed."} {"id": "PMID:1280624", "title": "The Anaplasma marginale msp5 gene encodes a 19-kilodalton protein conserved in all recognized Anaplasma species.", "content": "Immunization with Anaplasma marginale outer membranes induced immunity against clinical disease which correlated with antibody titer to outer membrane proteins, including a 19-kDa protein (N. Tebele, T. C. McGuire, and G. H. Palmer, Infect. Immun. 59:3199-3204, 1991). This 19-kDa protein, designated major surface protein 5 (MSP-5), was encoded by a single-copy 633-bp gene. The molecular mass of MSP-5, defined in immunoblots by binding to monoclonal antibody ANAF16C1, was conserved among all recognized species of Anaplasma: A. marginale, A. centrale, and A. ovis. Recombinant MSP-5, which absorbed the antibody reactivity of bovine immune serum to native MSP-5, was recognized by anti-A. marginale and anti-A. centrale immune sera in a competitive inhibition assay with monoclonal antibody ANAF16C1. The presence of antibody to the epitope defined by monoclonal antibody ANAF16C1 in all postinfection sera tested indicates that this epitope is a potential diagnostic antigen for use in identifying persistently infected cattle.", "contents": "The Anaplasma marginale msp5 gene encodes a 19-kilodalton protein conserved in all recognized Anaplasma species. Immunization with Anaplasma marginale outer membranes induced immunity against clinical disease which correlated with antibody titer to outer membrane proteins, including a 19-kDa protein (N. Tebele, T. C. McGuire, and G. H. Palmer, Infect. Immun. 59:3199-3204, 1991). This 19-kDa protein, designated major surface protein 5 (MSP-5), was encoded by a single-copy 633-bp gene. The molecular mass of MSP-5, defined in immunoblots by binding to monoclonal antibody ANAF16C1, was conserved among all recognized species of Anaplasma: A. marginale, A. centrale, and A. ovis. Recombinant MSP-5, which absorbed the antibody reactivity of bovine immune serum to native MSP-5, was recognized by anti-A. marginale and anti-A. centrale immune sera in a competitive inhibition assay with monoclonal antibody ANAF16C1. The presence of antibody to the epitope defined by monoclonal antibody ANAF16C1 in all postinfection sera tested indicates that this epitope is a potential diagnostic antigen for use in identifying persistently infected cattle."} {"id": "PMID:1280625", "title": "Modulation of endotoxin-induced monokine release in human monocytes by lipid A partial structures that inhibit binding of 125I-lipopolysaccharide.", "content": "We have previously shown that the synthetic tetraacyl precursor Ia (compound 406, LA-14-PP, or lipid IVa) was not able to induce the production of tumor necrosis factor, interleukin-1, and interleukin-6 in human monocytes but strongly antagonized lipopolysaccharide (LPS)-induced formation of these monokines. This inhibition was detectable at the level of mRNA production. To achieve a better understanding of molecular basis of this inhibition, we investigated whether lipid A precursor Ia (LA-14-PP), Escherichia coli-type lipid A (LA-15-PP), Chromobacterium violaceum-type lipid A (LA-22-PP), and synthetic lipid A partial structures and analogs (LA-23-PP, LA-24-PP, and PE-4) were able to influence the binding of 125I-LPS to human monocytes and compared this inhibitory activity with the agonistic and antagonistic action in the induction of monokines in human monocytes. 125I-LPS (20 ng per well) was added to human monocytes in the presence or absence of unlabeled rough Re mutant-derived LPS (Re-LPS) or lipid A compounds, and specific LPS binding was determined after 7 h. This binding was found to be dependent on CD14 as shown by the use of an anti-CD14 monoclonal antibody. Compound LA-14-PP was found to inhibit the binding of 125I-LPS to the cells in a similar dose-response to that of unlabeled LPS. This shows that the inhibitory capacity on LPS binding does not correlate with the monokine-inducing capacity because Re-LPS is active in inducing tumor necrosis factor, interleukin-1, and interleukin-6, while LA-14-PP is not. The strong capacity of LA-14-PP to inhibit 125I-LPS binding, however, correlates with the strong inhibitory capacity of this compound on LPS-induced monokine production. Compounds LA-15-PP, LA-23-PP, and LA-24-PP were active in the inhibition of 125I-LPS binding but were 5- to 10-fold weaker than Re-LPS and LA-14-PP. Of all lipid A structures tested, compound LA-22-PP expressed the weakest inhibitory capacity on LPS binding. These compounds showed again that the activity of binding inhibition does not correlate with the monokine-inducing capacity. We assume that the inhibitory effects of lipid A partial structures on LPS-induced monokine production have their origin in a competitive inhibition between LPS and the lipid A partial structures for the same binding site on the cell membrane.", "contents": "Modulation of endotoxin-induced monokine release in human monocytes by lipid A partial structures that inhibit binding of 125I-lipopolysaccharide. We have previously shown that the synthetic tetraacyl precursor Ia (compound 406, LA-14-PP, or lipid IVa) was not able to induce the production of tumor necrosis factor, interleukin-1, and interleukin-6 in human monocytes but strongly antagonized lipopolysaccharide (LPS)-induced formation of these monokines. This inhibition was detectable at the level of mRNA production. To achieve a better understanding of molecular basis of this inhibition, we investigated whether lipid A precursor Ia (LA-14-PP), Escherichia coli-type lipid A (LA-15-PP), Chromobacterium violaceum-type lipid A (LA-22-PP), and synthetic lipid A partial structures and analogs (LA-23-PP, LA-24-PP, and PE-4) were able to influence the binding of 125I-LPS to human monocytes and compared this inhibitory activity with the agonistic and antagonistic action in the induction of monokines in human monocytes. 125I-LPS (20 ng per well) was added to human monocytes in the presence or absence of unlabeled rough Re mutant-derived LPS (Re-LPS) or lipid A compounds, and specific LPS binding was determined after 7 h. This binding was found to be dependent on CD14 as shown by the use of an anti-CD14 monoclonal antibody. Compound LA-14-PP was found to inhibit the binding of 125I-LPS to the cells in a similar dose-response to that of unlabeled LPS. This shows that the inhibitory capacity on LPS binding does not correlate with the monokine-inducing capacity because Re-LPS is active in inducing tumor necrosis factor, interleukin-1, and interleukin-6, while LA-14-PP is not. The strong capacity of LA-14-PP to inhibit 125I-LPS binding, however, correlates with the strong inhibitory capacity of this compound on LPS-induced monokine production. Compounds LA-15-PP, LA-23-PP, and LA-24-PP were active in the inhibition of 125I-LPS binding but were 5- to 10-fold weaker than Re-LPS and LA-14-PP. Of all lipid A structures tested, compound LA-22-PP expressed the weakest inhibitory capacity on LPS binding. These compounds showed again that the activity of binding inhibition does not correlate with the monokine-inducing capacity. We assume that the inhibitory effects of lipid A partial structures on LPS-induced monokine production have their origin in a competitive inhibition between LPS and the lipid A partial structures for the same binding site on the cell membrane."} {"id": "PMID:1280626", "title": "Heterogeneity of monoclonal antibody-reactive epitopes on mycobacterial 30-kilodalton-region proteins and the secreted antigen 85 complex and demonstration of antigen 85B on the Mycobacterium leprae cell wall surface.", "content": "Proteins of the antigen 85 complex in the 30-kDa region secreted by live mycobacteria are important in the immune response against mycobacterial infections and may play an important biological role in the host-parasite interaction. In the present study, we have characterized epitopes of the 30-kDa-region proteins and the antigen 85 complex by using a panel of 13 monoclonal antibodies (MAbs) reacting with these antigens, 6 of which have not been described before. By using five previously characterized related secreted proteins of Mycobacterium tuberculosis, MPT44 (85A), MPT59 (85B), MPT45 (85C), MPT51 (27 kDa), and MPT64 (26 kDa), we have identified at least 10 different MAb-reactive epitopes on the proteins of the antigen 85 complex. A heterogeneous distribution of epitopes was observed within the components of the antigen 85 complex. Two distinct epitopes specific for antigen 85B and two other epitopes restricted to the 85A and 85B components were recognized. Two of them were shared with a previously unidentified 27-kDa protein present in M. tuberculosis culture fluid from which all MPT proteins were derived. The rest of the MAb-reactive epitopes were found to be present mostly in antigens 85A and 85B and to a lesser extent in antigen 85C. None of these MAbs recognized component 85C alone nor did they bind to the related MPT51 and MPT64 proteins. Interestingly, most of the MAbs reacted with purified native proteins of the antigen 85 complex but not to them in their denatured forms. In contrast, reactivity of the MAbs with the cytosol fraction of M. tuberculosis in immunoblotting revealed that they bound to a closely related cytosolic 30-kDa protein(s) even when they were denatured. Heterogeneity of these MAb-reactive epitopes of the antigen 85 complex was further evident as they were found to be distributed in various patterns among 19 different mycobacterial species. By using fusion proteins of the Mycobacterium leprae 30/31-kDa antigen 85 complex, we have localized at least six different epitopes within amino acid residues 55 to 266 of the M. leprae antigen 85 complex. Finally, by immunohistochemical analysis, we have demonstrated the in situ expression of one of the novel MAb-reactive epitopes specific for antigen 85B on the cell wall surface of M. leprae within macrophages in lepromatous leprosy lesions and thus provide direct evidence for the presence of the B component of the antigen 85 complex on the surface of intact M. leprae.", "contents": "Heterogeneity of monoclonal antibody-reactive epitopes on mycobacterial 30-kilodalton-region proteins and the secreted antigen 85 complex and demonstration of antigen 85B on the Mycobacterium leprae cell wall surface. Proteins of the antigen 85 complex in the 30-kDa region secreted by live mycobacteria are important in the immune response against mycobacterial infections and may play an important biological role in the host-parasite interaction. In the present study, we have characterized epitopes of the 30-kDa-region proteins and the antigen 85 complex by using a panel of 13 monoclonal antibodies (MAbs) reacting with these antigens, 6 of which have not been described before. By using five previously characterized related secreted proteins of Mycobacterium tuberculosis, MPT44 (85A), MPT59 (85B), MPT45 (85C), MPT51 (27 kDa), and MPT64 (26 kDa), we have identified at least 10 different MAb-reactive epitopes on the proteins of the antigen 85 complex. A heterogeneous distribution of epitopes was observed within the components of the antigen 85 complex. Two distinct epitopes specific for antigen 85B and two other epitopes restricted to the 85A and 85B components were recognized. Two of them were shared with a previously unidentified 27-kDa protein present in M. tuberculosis culture fluid from which all MPT proteins were derived. The rest of the MAb-reactive epitopes were found to be present mostly in antigens 85A and 85B and to a lesser extent in antigen 85C. None of these MAbs recognized component 85C alone nor did they bind to the related MPT51 and MPT64 proteins. Interestingly, most of the MAbs reacted with purified native proteins of the antigen 85 complex but not to them in their denatured forms. In contrast, reactivity of the MAbs with the cytosol fraction of M. tuberculosis in immunoblotting revealed that they bound to a closely related cytosolic 30-kDa protein(s) even when they were denatured. Heterogeneity of these MAb-reactive epitopes of the antigen 85 complex was further evident as they were found to be distributed in various patterns among 19 different mycobacterial species. By using fusion proteins of the Mycobacterium leprae 30/31-kDa antigen 85 complex, we have localized at least six different epitopes within amino acid residues 55 to 266 of the M. leprae antigen 85 complex. Finally, by immunohistochemical analysis, we have demonstrated the in situ expression of one of the novel MAb-reactive epitopes specific for antigen 85B on the cell wall surface of M. leprae within macrophages in lepromatous leprosy lesions and thus provide direct evidence for the presence of the B component of the antigen 85 complex on the surface of intact M. leprae."} {"id": "PMID:1280627", "title": "Molecular analysis of the P2 porin protein of nontypeable Haemophilus influenzae.", "content": "The P2 porin protein is the most abundant outer membrane protein (OMP) of nontypeable Haemophilus influenzae (NTHI) and shows extensive antigenic heterogeneity among strains. To study the molecular basis of this heterogeneity, the DNA sequences of the genes encoding the P2 proteins of three unrelated strains of NTHI were determined, and restriction fragment length polymorphisms around the P2 genes of 35 strains were analyzed. The deduced amino acid sequences of the P2 genes from the three strains of NTHI revealed four major (12 to 35 amino acids long) and several smaller (2 to 7 amino acids) hypervariable regions in each protein. The major variations occurred in identical portions of the genes, and these regions showed a high antigenic index and surface exposure probability in computer modeling analysis. Differences in the molecular mass of the P2 protein correlate with differences in the size of the variable region in each strain. Oligonucleotide primers suitable for amplification of the P2 genes by polymerase chain reaction were developed. Restriction fragment length polymorphism analysis showed marked heterogeneity in and around the ompP2 locus of 35 NTHI strains. These results contrast with the high degree of conservation of the P2 genes in H. influenzae type b strains. We conclude that the molecular mass and antigenic heterogeneity of the P2 molecule of NTHI is due to variations in gene sequence that are clustered primarily in four large hypervariable regions of the gene.", "contents": "Molecular analysis of the P2 porin protein of nontypeable Haemophilus influenzae. The P2 porin protein is the most abundant outer membrane protein (OMP) of nontypeable Haemophilus influenzae (NTHI) and shows extensive antigenic heterogeneity among strains. To study the molecular basis of this heterogeneity, the DNA sequences of the genes encoding the P2 proteins of three unrelated strains of NTHI were determined, and restriction fragment length polymorphisms around the P2 genes of 35 strains were analyzed. The deduced amino acid sequences of the P2 genes from the three strains of NTHI revealed four major (12 to 35 amino acids long) and several smaller (2 to 7 amino acids) hypervariable regions in each protein. The major variations occurred in identical portions of the genes, and these regions showed a high antigenic index and surface exposure probability in computer modeling analysis. Differences in the molecular mass of the P2 protein correlate with differences in the size of the variable region in each strain. Oligonucleotide primers suitable for amplification of the P2 genes by polymerase chain reaction were developed. Restriction fragment length polymorphism analysis showed marked heterogeneity in and around the ompP2 locus of 35 NTHI strains. These results contrast with the high degree of conservation of the P2 genes in H. influenzae type b strains. We conclude that the molecular mass and antigenic heterogeneity of the P2 molecule of NTHI is due to variations in gene sequence that are clustered primarily in four large hypervariable regions of the gene."} {"id": "PMID:1280628", "title": "Enhancement of host defense by Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, a novel synthetic compound. A comparison with recombinant human granulocyte colony-stimulating factor in 5-fluorouracil-treated mice.", "content": "The effect of a novel synthetic compound, Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, on recovery from long-lasting leukopenia induced by 5-fluorouracil was compared with that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). When mice were administered i.p. with 5-FU (200 mg/kg) on days 0 and 7, intravenous administration of Y-25510 (100 and 1000 micrograms/kg) prevented the decrease in the peripheral leukocyte and neutrophil number and accelerated the recovery from leukopenia. Subcutaneous administration of rhG-CSF (50 micrograms/kg) did not prevent leukopenia but accelerated the recovery from leukopenia. In particular, peripheral neutrophil number increased over a normal level. The administration of Y-25510 (10, 100 and 1000 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, lymphocytes, neutrophils and monocytes. The administration of rhG-CSF (50 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, and neutrophils but not that of lymphocytes and monocytes. In fractions of bone marrow cells on day 21, the administration of Y-25510 (1000 micrograms/kg) showed a tendency of restoring the decrease in neutrophil number. In conclusion, the administration of Y-25510 prevented leukopenia and accelerated the recovery from leukopenia in the 5-FU-treated mice. It is suggested that the mechanism of the restorative action of Y-25510 is different from that of rhG-CSF. In a number of immature bone marrow cells Y-25510 has a potent stimulatory effect on the recovery from the decrease in number of hematopoietic cells, keeping a balance in number of each blood cell.", "contents": "Enhancement of host defense by Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, a novel synthetic compound. A comparison with recombinant human granulocyte colony-stimulating factor in 5-fluorouracil-treated mice. The effect of a novel synthetic compound, Y-25510, (+-)-3-[4-(2-dimethylamino-1-methylethoxy)phenyl]-1H-pyrazolo[3,4 -b] pyridine-1-acetic acid, on recovery from long-lasting leukopenia induced by 5-fluorouracil was compared with that of recombinant human granulocyte colony-stimulating factor (rhG-CSF). When mice were administered i.p. with 5-FU (200 mg/kg) on days 0 and 7, intravenous administration of Y-25510 (100 and 1000 micrograms/kg) prevented the decrease in the peripheral leukocyte and neutrophil number and accelerated the recovery from leukopenia. Subcutaneous administration of rhG-CSF (50 micrograms/kg) did not prevent leukopenia but accelerated the recovery from leukopenia. In particular, peripheral neutrophil number increased over a normal level. The administration of Y-25510 (10, 100 and 1000 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, lymphocytes, neutrophils and monocytes. The administration of rhG-CSF (50 micrograms/kg) restored the decrease in the number of bone marrow cells, spleen cells, and neutrophils but not that of lymphocytes and monocytes. In fractions of bone marrow cells on day 21, the administration of Y-25510 (1000 micrograms/kg) showed a tendency of restoring the decrease in neutrophil number. In conclusion, the administration of Y-25510 prevented leukopenia and accelerated the recovery from leukopenia in the 5-FU-treated mice. It is suggested that the mechanism of the restorative action of Y-25510 is different from that of rhG-CSF. In a number of immature bone marrow cells Y-25510 has a potent stimulatory effect on the recovery from the decrease in number of hematopoietic cells, keeping a balance in number of each blood cell."} {"id": "PMID:1280629", "title": "Protective effect of ren-shen-yang-rong-tang (Ninjin-youei-to) in mice with drug-induced leukopenia against Pseudomonas aeruginosa infection.", "content": "When 200 mg/kg of cyclophosphamide (CY) or 5-fluorouracil (5-FU) were given subcutaneously to mice, severe reduction of leukocyte numbers in the peripheral blood was observed on day 4 and from day 4 to day 8 after the treatment, respectively. Daily administration of ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT), (1 g/kg/day) and recombinant human granulocyte-colony stimulating factor (rhuG-CSF, 2 micrograms/mouse/day) either from day 0 to day 4 after treatment with CY or from day 0 to day 8 after treatment with 5-FU accelerated the recovery of peripheral leukocytes. Administration of NYT and rhuG-CSF inhibited decreases in the number of colony forming units in the spleen (CFU-S) in drug-treated mice. In mice infected intraperitoneally with a virulent strain of Pseudomonas aeruginosa 4 days and 8 days after treatment with CY and 5-FU, respectively, lethal doses were much lower (approximately 1/1000) than that in normal mice. Administration of NYT and rhuG-CSF to drug-treated mice inhibited the enhanced bacterial growth in the peritoneal cavity. Administration of NYT or rhuG-CSF to drug-treated mice enhanced the recovery of accumulation of leukocytes into the infected peritoneal cavity from their depressed state. Administration of NYT was more effective for improving the host resistance of 5-FU-treated mice than for improving that of CY-treated mice in contrast to rhuG-CSF which exhibited stronger effect in CY-treated mice than in 5-FU treated mice.", "contents": "Protective effect of ren-shen-yang-rong-tang (Ninjin-youei-to) in mice with drug-induced leukopenia against Pseudomonas aeruginosa infection. When 200 mg/kg of cyclophosphamide (CY) or 5-fluorouracil (5-FU) were given subcutaneously to mice, severe reduction of leukocyte numbers in the peripheral blood was observed on day 4 and from day 4 to day 8 after the treatment, respectively. Daily administration of ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NYT), (1 g/kg/day) and recombinant human granulocyte-colony stimulating factor (rhuG-CSF, 2 micrograms/mouse/day) either from day 0 to day 4 after treatment with CY or from day 0 to day 8 after treatment with 5-FU accelerated the recovery of peripheral leukocytes. Administration of NYT and rhuG-CSF inhibited decreases in the number of colony forming units in the spleen (CFU-S) in drug-treated mice. In mice infected intraperitoneally with a virulent strain of Pseudomonas aeruginosa 4 days and 8 days after treatment with CY and 5-FU, respectively, lethal doses were much lower (approximately 1/1000) than that in normal mice. Administration of NYT and rhuG-CSF to drug-treated mice inhibited the enhanced bacterial growth in the peritoneal cavity. Administration of NYT or rhuG-CSF to drug-treated mice enhanced the recovery of accumulation of leukocytes into the infected peritoneal cavity from their depressed state. Administration of NYT was more effective for improving the host resistance of 5-FU-treated mice than for improving that of CY-treated mice in contrast to rhuG-CSF which exhibited stronger effect in CY-treated mice than in 5-FU treated mice."} {"id": "PMID:1280633", "title": "A new histological embedding method by low-temperature polymerisation of methyl methacrylate allowing immuno- and enzyme histochemical studies on semi-thin sections of undecalcified bone marrow biopsies.", "content": "A new procedure of embedding in methyl methacrylate (MMA) is introduced, which enables immunostaining by preservation of cellular epitopes. This could be achieved by reduction of polymerisation temperature from ca. 60 degrees C to 22 degrees C within the core of tissue blocks. Reduction of the polymerisation temperature is due to destabilisation of acrylate monomer, reduction of catalyst, exclusion of molecular oxygen, chemical initiation and reduction of environmental temperature. This results in good preservation of antigens and enzymes in the haematopoietic and lymphatic tissue of bone marrow as well as lymphoid, epithelial and mesenchymal markers in other tissues, comparable to paraffin embedding. Results are demonstrated by application of monoclonal and polyclonal antibodies and by demonstration of enzyme activity conventionally used in haematology.", "contents": "A new histological embedding method by low-temperature polymerisation of methyl methacrylate allowing immuno- and enzyme histochemical studies on semi-thin sections of undecalcified bone marrow biopsies. A new procedure of embedding in methyl methacrylate (MMA) is introduced, which enables immunostaining by preservation of cellular epitopes. This could be achieved by reduction of polymerisation temperature from ca. 60 degrees C to 22 degrees C within the core of tissue blocks. Reduction of the polymerisation temperature is due to destabilisation of acrylate monomer, reduction of catalyst, exclusion of molecular oxygen, chemical initiation and reduction of environmental temperature. This results in good preservation of antigens and enzymes in the haematopoietic and lymphatic tissue of bone marrow as well as lymphoid, epithelial and mesenchymal markers in other tissues, comparable to paraffin embedding. Results are demonstrated by application of monoclonal and polyclonal antibodies and by demonstration of enzyme activity conventionally used in haematology."} {"id": "PMID:1280634", "title": "Human carcinoma cells synthesize and secrete tenascin in vitro.", "content": "Tenascin is an extracellular matrix glycoprotein produced in response to epithelial-mesenchymal interactions that initiate fetal organogenesis, and it is also found in the stroma of benign and malignant neoplasms. Thirty-five human cell lines representing a variety of cancers were examined by immunoprecipitation and polyacrylamide gel electrophoresis of radiolabeled tenascin proteins from conditioned media. Two forms of tenascin with relative molecular masses of 190,000 and 250,000 were identified. Eight cell lines produced both forms. With the exception of myeloid and lymphoid leukemias and Burkitt's lymphoma, all of the mesodermal and neuroectodermal tumor lines were found to synthesize tenascin. Unexpectedly, tenascin was secreted by several mammary and colonic adenocarcinomas as well as by a line derived from normal mammary epithelial cells, and in some cases increased production was induced by transforming growth factor beta in serum-free medium. Cells producing fibronectin but not tenascin attached and spread on plastic culture dishes, while those producing tenascin alone remained suspended in the medium or were rarely attached. Tenascin also inhibited fibronectin-mediated adhesion of MCF7 breast carcinoma cells in vitro. The results suggest that tenascins synthesized and secreted by some cancer cells, especially those of epithelial origin, may have specific roles in determining tumor cell adhesion and ultimately the ability to form invasive outgrowths.", "contents": "Human carcinoma cells synthesize and secrete tenascin in vitro. Tenascin is an extracellular matrix glycoprotein produced in response to epithelial-mesenchymal interactions that initiate fetal organogenesis, and it is also found in the stroma of benign and malignant neoplasms. Thirty-five human cell lines representing a variety of cancers were examined by immunoprecipitation and polyacrylamide gel electrophoresis of radiolabeled tenascin proteins from conditioned media. Two forms of tenascin with relative molecular masses of 190,000 and 250,000 were identified. Eight cell lines produced both forms. With the exception of myeloid and lymphoid leukemias and Burkitt's lymphoma, all of the mesodermal and neuroectodermal tumor lines were found to synthesize tenascin. Unexpectedly, tenascin was secreted by several mammary and colonic adenocarcinomas as well as by a line derived from normal mammary epithelial cells, and in some cases increased production was induced by transforming growth factor beta in serum-free medium. Cells producing fibronectin but not tenascin attached and spread on plastic culture dishes, while those producing tenascin alone remained suspended in the medium or were rarely attached. Tenascin also inhibited fibronectin-mediated adhesion of MCF7 breast carcinoma cells in vitro. The results suggest that tenascins synthesized and secreted by some cancer cells, especially those of epithelial origin, may have specific roles in determining tumor cell adhesion and ultimately the ability to form invasive outgrowths."} {"id": "PMID:1280631", "title": "Influence of glucocorticoid, aspirin, and gamma globulin on interleukin-6 production in the hepatoma cell line.", "content": "The current study was designed to observe the effects of drugs used for the treatment of inflammatory diseases (glucocorticoid, aspirin, and gamma globulin) on interleukin 6 (IL-6) production in the liver which may be involved in acute phase protein stimulation. The HUH-7 hepatoma cell line was used in which the IL-6 gene is expressed and produces IL-6 in vitro. The cells were cultured in RPMI 1640 supplemented with 1% fetal calf serum for 12 h prior to addition of these drugs. We collected the cells and supernatants at 24 h, 48 h, and 72 h after addition of glucocorticoid, aspirin, and gamma globulin. IL-6 mRNA in the cells was measured by Northern blot hybridization, while the IL-6 activity in culture supernatants was measured by enzyme-linked immunosorbent assay. At 48 h after addition of glucocorticoid and aspirin, there was a suppression of IL-6 activity in the culture supernatants, which was associated with a decrease of mRNA level in the cells. However, suppression by gamma globulin was not observed. These data demonstrate that glucocorticoid and aspirin are potent regulators of IL-6 synthesis in the hepatoma cell. These components may decrease acute phase protein production via the suppression of IL-6 production in the liver during inflammation.", "contents": "Influence of glucocorticoid, aspirin, and gamma globulin on interleukin-6 production in the hepatoma cell line. The current study was designed to observe the effects of drugs used for the treatment of inflammatory diseases (glucocorticoid, aspirin, and gamma globulin) on interleukin 6 (IL-6) production in the liver which may be involved in acute phase protein stimulation. The HUH-7 hepatoma cell line was used in which the IL-6 gene is expressed and produces IL-6 in vitro. The cells were cultured in RPMI 1640 supplemented with 1% fetal calf serum for 12 h prior to addition of these drugs. We collected the cells and supernatants at 24 h, 48 h, and 72 h after addition of glucocorticoid, aspirin, and gamma globulin. IL-6 mRNA in the cells was measured by Northern blot hybridization, while the IL-6 activity in culture supernatants was measured by enzyme-linked immunosorbent assay. At 48 h after addition of glucocorticoid and aspirin, there was a suppression of IL-6 activity in the culture supernatants, which was associated with a decrease of mRNA level in the cells. However, suppression by gamma globulin was not observed. These data demonstrate that glucocorticoid and aspirin are potent regulators of IL-6 synthesis in the hepatoma cell. These components may decrease acute phase protein production via the suppression of IL-6 production in the liver during inflammation."} {"id": "PMID:1280632", "title": "Influence of staurosporine, a more selective derivative CGP 41,251 and an inactive analogue CGP 42,700 on histamine release from isolated rat mast cells.", "content": "The influence of staurosporine, a potent but nonselective inhibitor of protein kinase C, on rat mast cell histamine release, was compared with that of two derivatives, CGP 41,251 with a high degree of selectivity for protein kinase C and the related CGP 42,700 which is without activity. Staurosporine was a more potent inhibitor of mast cell responses than CGP 41,251, in accordance with their reported potencies. CGP 42,700 was investigated in the same concentration range as CGP 41,251 and served as a control for unspecific effects. Antigen induced histamine release was more effectively inhibited by staurosporine than by CGP 41,251, and responses to compound 48/80 were only modestly affected by both drugs. Responses to the ionophore A23187 were unaffected by staurosporine whereas CGP 41,251 was an effective inhibitor at suboptimal ionophore concentrations. In contrast, responses to combinations of the phorbol ester TPA and subthreshold concentrations of the ionophore could be potently inhibited by staurosporine but were under certain conditions moderately enhanced by lower concentrations of the drug, whereas CGP 41,251 was only inhibitory. Except for a slight inhibition of ionophore responses CGP 42,700 was without effect. The results demonstrate that the actions of staurosporine cannot be ascribed solely to inhibition of protein kinase C, whereas the influence of CGP 41,251 appears to be consistent with an inhibition of this kinase.", "contents": "Influence of staurosporine, a more selective derivative CGP 41,251 and an inactive analogue CGP 42,700 on histamine release from isolated rat mast cells. The influence of staurosporine, a potent but nonselective inhibitor of protein kinase C, on rat mast cell histamine release, was compared with that of two derivatives, CGP 41,251 with a high degree of selectivity for protein kinase C and the related CGP 42,700 which is without activity. Staurosporine was a more potent inhibitor of mast cell responses than CGP 41,251, in accordance with their reported potencies. CGP 42,700 was investigated in the same concentration range as CGP 41,251 and served as a control for unspecific effects. Antigen induced histamine release was more effectively inhibited by staurosporine than by CGP 41,251, and responses to compound 48/80 were only modestly affected by both drugs. Responses to the ionophore A23187 were unaffected by staurosporine whereas CGP 41,251 was an effective inhibitor at suboptimal ionophore concentrations. In contrast, responses to combinations of the phorbol ester TPA and subthreshold concentrations of the ionophore could be potently inhibited by staurosporine but were under certain conditions moderately enhanced by lower concentrations of the drug, whereas CGP 41,251 was only inhibitory. Except for a slight inhibition of ionophore responses CGP 42,700 was without effect. The results demonstrate that the actions of staurosporine cannot be ascribed solely to inhibition of protein kinase C, whereas the influence of CGP 41,251 appears to be consistent with an inhibition of this kinase."} {"id": "PMID:1280635", "title": "Optimal electric conditions in electrical impulse chemotherapy.", "content": "The relationship was examined between the tumoricidal effect and the electrical variables of in vivo electrical impulse chemotherapy. Donryu rats subcutaneously inoculated with AH-109AY hepatocellular carcinomas were given a single high-voltage electrical impulse of varying voltage and duration, 30 min after an intramuscular injection of 4 mg/kg bleomycin. As the voltage (V) was increased from 0 to 5 kV, the tumoricidal effect (E) increased in proportion to the square of the voltage. As the pulse duration (D) was increased from 2.5 to 5.8 ms, the tumoricidal effect increased in direct proportion to it. Combining these results yielded the formula, E = gamma V2D, which indicates that tumoricidal efficacy was proportional to the applied electrical energy. When the electrical energy was kept constant while varying the voltage and duration of pulse, the anticancer effect was the same, confirming this relationship for lower energy levels.", "contents": "Optimal electric conditions in electrical impulse chemotherapy. The relationship was examined between the tumoricidal effect and the electrical variables of in vivo electrical impulse chemotherapy. Donryu rats subcutaneously inoculated with AH-109AY hepatocellular carcinomas were given a single high-voltage electrical impulse of varying voltage and duration, 30 min after an intramuscular injection of 4 mg/kg bleomycin. As the voltage (V) was increased from 0 to 5 kV, the tumoricidal effect (E) increased in proportion to the square of the voltage. As the pulse duration (D) was increased from 2.5 to 5.8 ms, the tumoricidal effect increased in direct proportion to it. Combining these results yielded the formula, E = gamma V2D, which indicates that tumoricidal efficacy was proportional to the applied electrical energy. When the electrical energy was kept constant while varying the voltage and duration of pulse, the anticancer effect was the same, confirming this relationship for lower energy levels."} {"id": "PMID:1280636", "title": "Cytochemical localisation and characterisation of proteoglycans (glycosaminoglycans) in the epithelial-stromal interface of the seminal vesicle of the guinea pig.", "content": "The proteoglycans (PGs) in the guinea pig seminal vesicle were demonstrated ultrastructurally by both cuprolinic blue (CB) and ruthenium red (RR) staining. The PGs appeared as electron-dense granules with RR, but were filamentous following CB staining using the critical electrolyte concentration method. Three major types of PGs (T1, T2, T3) have been described according to their different locations and sizes. T1 filaments were short and were found mostly on both sides of the lamina densa of the basal lamina of the glandular epithelium (40-60 nm long) and also on the basal laminae of smooth muscle cells and capillary endothelial cells (20-30 nm long). In the epithelial basal lamina they were regularly spaced at an interval of 40-60 nm. T1 filaments in the lamina densa were smaller and more randomly distributed. Cytochemical characterisation of these PGs by various GAG degrading enzymes showed that T1 PGs are rich in heparan sulphate. T2 filaments were 30-40 nm long and closely associated with the collagen fibrils. They were arranged perpendicular to the long axis of collagen fibrils, also at intervals of about 60 nm. T2 filaments were removed by chondroitinase (Ch)-ABC, Ch-ABC plus Streptomyces (S)-hyaluronidase and pronase, but resistant to nitrous acid, heparitinase, heparinase, neuraminidase and S-hyaluronidase. These show that T2 filaments are rich in dermatan sulphate. T3 filaments (60-100 nm) were widely distributed in the stroma at sites such as the interstitial spaces of the lamina propria, the reticular layer below the basal lamina, around individual collagen fibrils or bundles of such fibres, and on the cell surfaces of fibroblasts. The T3 filaments were removed by Ch-ABC, Ch-AC and pronase but were resistant to heparitinase, heparinase, S-hyaluronidase, neuraminidase and nitrous acid. They are therefore rich in chondroitin sulphate.", "contents": "Cytochemical localisation and characterisation of proteoglycans (glycosaminoglycans) in the epithelial-stromal interface of the seminal vesicle of the guinea pig. The proteoglycans (PGs) in the guinea pig seminal vesicle were demonstrated ultrastructurally by both cuprolinic blue (CB) and ruthenium red (RR) staining. The PGs appeared as electron-dense granules with RR, but were filamentous following CB staining using the critical electrolyte concentration method. Three major types of PGs (T1, T2, T3) have been described according to their different locations and sizes. T1 filaments were short and were found mostly on both sides of the lamina densa of the basal lamina of the glandular epithelium (40-60 nm long) and also on the basal laminae of smooth muscle cells and capillary endothelial cells (20-30 nm long). In the epithelial basal lamina they were regularly spaced at an interval of 40-60 nm. T1 filaments in the lamina densa were smaller and more randomly distributed. Cytochemical characterisation of these PGs by various GAG degrading enzymes showed that T1 PGs are rich in heparan sulphate. T2 filaments were 30-40 nm long and closely associated with the collagen fibrils. They were arranged perpendicular to the long axis of collagen fibrils, also at intervals of about 60 nm. T2 filaments were removed by chondroitinase (Ch)-ABC, Ch-ABC plus Streptomyces (S)-hyaluronidase and pronase, but resistant to nitrous acid, heparitinase, heparinase, neuraminidase and S-hyaluronidase. These show that T2 filaments are rich in dermatan sulphate. T3 filaments (60-100 nm) were widely distributed in the stroma at sites such as the interstitial spaces of the lamina propria, the reticular layer below the basal lamina, around individual collagen fibrils or bundles of such fibres, and on the cell surfaces of fibroblasts. The T3 filaments were removed by Ch-ABC, Ch-AC and pronase but were resistant to heparitinase, heparinase, S-hyaluronidase, neuraminidase and nitrous acid. They are therefore rich in chondroitin sulphate."} {"id": "PMID:1280637", "title": "Oncogene.", "content": "Recent studies have shown that activation of oncogenes, genes concerned with cell growth, and inactivation of anti-oncogenes may be responsible for uncontrolled cell proliferation leading to malignancy. These oncogenes code for products or proteins which are closely similar to growth factors or receptors of growth factors. Alterations in lipid metabolism in the form of excess formation of inositol triphosphate and relocation of protein kinase C, the second messengers of the mitotic process, can initiate cell division. Oncogenes can be activated by chromosomal aberrations induced by chemicals, viruses and drugs. The identification of oncogenes and their products may have relevance to the development of new therapeutic strategies in cancer.", "contents": "Oncogene. Recent studies have shown that activation of oncogenes, genes concerned with cell growth, and inactivation of anti-oncogenes may be responsible for uncontrolled cell proliferation leading to malignancy. These oncogenes code for products or proteins which are closely similar to growth factors or receptors of growth factors. Alterations in lipid metabolism in the form of excess formation of inositol triphosphate and relocation of protein kinase C, the second messengers of the mitotic process, can initiate cell division. Oncogenes can be activated by chromosomal aberrations induced by chemicals, viruses and drugs. The identification of oncogenes and their products may have relevance to the development of new therapeutic strategies in cancer."} {"id": "PMID:1280639", "title": "Detection of HTLV-I in clinical specimens.", "content": "The American Red Cross, which collects 50% of blood for transfusion in the United States, now tests all prospective blood donors for HTLV-I and HTLV-II antibodies. It will therefore be important to recognize the significance and clinical spectrum of diseases associated with these viruses, and to become familiar with the current methods used to diagnose infection. This review summarizes the techniques currently in use to screen for HTLV-I/II antibodies, as well as methods to detect viral genome and/or gene products in blood and tissue specimens.", "contents": "Detection of HTLV-I in clinical specimens. The American Red Cross, which collects 50% of blood for transfusion in the United States, now tests all prospective blood donors for HTLV-I and HTLV-II antibodies. It will therefore be important to recognize the significance and clinical spectrum of diseases associated with these viruses, and to become familiar with the current methods used to diagnose infection. This review summarizes the techniques currently in use to screen for HTLV-I/II antibodies, as well as methods to detect viral genome and/or gene products in blood and tissue specimens."} {"id": "PMID:1280640", "title": "A non-radioisotopic reverse transcriptase assay using biotin-11-deoxyuridinetriphosphate on primer-immobilized microtiter plates.", "content": "We developed a non-radioisotopic (non-RI) reverse transcriptase assay (RTA). The reverse transcriptase (RT) incorporates biotin-11-deoxyuridine-triphosphate (bio-dUTP) using a poly(rA) template hybridized with oligo(dT) primer that is immobilized on the surface of a 96-well microtiter plate. This assay is thus semi-automated by adapting it to an ELISA testing format. The incorporation of bio-dUTP was enhanced by adding cold dTTP to the reaction mixture, optimally in a molar ratio 4:1 (dTTP:bio-dUTP). This non-RI RTA is more sensitive than the conventional RI assay for the detection of purified Rous-associated virus 2 (RAV-2) and of human immunodeficiency virus type 1 (HIV-1) lysate. Because of its simple procedure, higher sensitivity and non-use of RI materials, the assay can be utilized not only for virological studies but also for routine safety screening of biological products for retroviral contamination.", "contents": "A non-radioisotopic reverse transcriptase assay using biotin-11-deoxyuridinetriphosphate on primer-immobilized microtiter plates. We developed a non-radioisotopic (non-RI) reverse transcriptase assay (RTA). The reverse transcriptase (RT) incorporates biotin-11-deoxyuridine-triphosphate (bio-dUTP) using a poly(rA) template hybridized with oligo(dT) primer that is immobilized on the surface of a 96-well microtiter plate. This assay is thus semi-automated by adapting it to an ELISA testing format. The incorporation of bio-dUTP was enhanced by adding cold dTTP to the reaction mixture, optimally in a molar ratio 4:1 (dTTP:bio-dUTP). This non-RI RTA is more sensitive than the conventional RI assay for the detection of purified Rous-associated virus 2 (RAV-2) and of human immunodeficiency virus type 1 (HIV-1) lysate. Because of its simple procedure, higher sensitivity and non-use of RI materials, the assay can be utilized not only for virological studies but also for routine safety screening of biological products for retroviral contamination."} {"id": "PMID:1280641", "title": "Genetic heterogeneity within Mycobacterium fortuitum complex species: genotypic criteria for identification.", "content": "A 1.5-kb segment of the DNA that encodes 16S rRNA was amplified by polymerase chain reaction, and 880 nucleotide positions were determined from each of the described biovariants of Mycobacterium fortuitum. Signature sequences which allow rapid identification of M. fortuitum strains at the biovariant level are described. Our data demonstrate a close phylogenetic relationship between Mycobacterium senegalense and M. fortuitum and indicate that the described biovariants of M. fortuitum represent genetically distinct taxa.", "contents": "Genetic heterogeneity within Mycobacterium fortuitum complex species: genotypic criteria for identification. A 1.5-kb segment of the DNA that encodes 16S rRNA was amplified by polymerase chain reaction, and 880 nucleotide positions were determined from each of the described biovariants of Mycobacterium fortuitum. Signature sequences which allow rapid identification of M. fortuitum strains at the biovariant level are described. Our data demonstrate a close phylogenetic relationship between Mycobacterium senegalense and M. fortuitum and indicate that the described biovariants of M. fortuitum represent genetically distinct taxa."} {"id": "PMID:1280642", "title": "Infection with a plasmid-free variant Chlamydia related to Chlamydia trachomatis identified by using multiple assays for nucleic acid detection.", "content": "Clinical samples in transport media from 40 patients exhibiting pathologies potentially caused by Chlamydia trachomatis infection were analyzed for chlamydial nucleic acid, and the results were compared with those of culture. Chlamydial culture was performed by a shell vial centrifugation method with HeLa 229 host cells. Polymerase chain reaction (PCR) assays were used to detect either regions on a 7.5-kb plasmid characteristic of C. trachomatis (plasmid-PCR) or a segment of the 16S rRNA genes (rRNA-PCR). All PCR results were confirmed by hybridization with probes for the specific amplified products in either a Southern or a dot blot format. An RNase protection (RNP) assay was used to detect genus-specific chlamydial 16S rRNA directly from the clinical samples. The PCR assays detected C. trachomatis but not other bacteria, including Chlamydia spp. C. trachomatis was isolated from six samples which were positive by the rDNA-PCR and plasmid-PCR assays. Five of the culture-positive specimens were positive by the RNP assay. Twenty-two samples were negative by all criteria. Surprisingly, nine samples were positive by rRNA-PCR and RNP assays only. Nucleic acid sequencing of the rRNA-PCR-amplified products indicated a close relationship between the variants and C. trachomatis. The data may indicate an unrecognized process in C. trachomatis infection or that these patients were infected by a variant strain of C. trachomatis which lacks the C. trachomatis-specific plasmid.", "contents": "Infection with a plasmid-free variant Chlamydia related to Chlamydia trachomatis identified by using multiple assays for nucleic acid detection. Clinical samples in transport media from 40 patients exhibiting pathologies potentially caused by Chlamydia trachomatis infection were analyzed for chlamydial nucleic acid, and the results were compared with those of culture. Chlamydial culture was performed by a shell vial centrifugation method with HeLa 229 host cells. Polymerase chain reaction (PCR) assays were used to detect either regions on a 7.5-kb plasmid characteristic of C. trachomatis (plasmid-PCR) or a segment of the 16S rRNA genes (rRNA-PCR). All PCR results were confirmed by hybridization with probes for the specific amplified products in either a Southern or a dot blot format. An RNase protection (RNP) assay was used to detect genus-specific chlamydial 16S rRNA directly from the clinical samples. The PCR assays detected C. trachomatis but not other bacteria, including Chlamydia spp. C. trachomatis was isolated from six samples which were positive by the rDNA-PCR and plasmid-PCR assays. Five of the culture-positive specimens were positive by the RNP assay. Twenty-two samples were negative by all criteria. Surprisingly, nine samples were positive by rRNA-PCR and RNP assays only. Nucleic acid sequencing of the rRNA-PCR-amplified products indicated a close relationship between the variants and C. trachomatis. The data may indicate an unrecognized process in C. trachomatis infection or that these patients were infected by a variant strain of C. trachomatis which lacks the C. trachomatis-specific plasmid."} {"id": "PMID:1280643", "title": "Development of polymerase chain reaction primer sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis.", "content": "We have determined and compared partial 16S rRNA sequences from 23 Lyme disease spirochete isolates and aligned these with 8 sequences previously presented. The 16S rRNA signature nucleotide compositions were defined for each isolate and compared with the genomic species signature nucleotide sets previously established. To identify positions truly indicative of species classification which could serve as targets for polymerase chain reaction species-specific identification primers, 16S rRNA-based phylogenetic analyses were conducted. On the basis of the identified signature nucleotides, we designed polymerase chain reaction primer sets which (i) amplify all spirochete species associated with Lyme disease and (ii) differentiate between these species. The primer sets were tested on 38 Borrelia isolates associated with Lyme disease and were found to be sensitive and specific. All Lyme disease isolates tested were amplification positive. These primers allow for the rapid species identification of Lyme disease isolates.", "contents": "Development of polymerase chain reaction primer sets for diagnosis of Lyme disease and for species-specific identification of Lyme disease isolates by 16S rRNA signature nucleotide analysis. We have determined and compared partial 16S rRNA sequences from 23 Lyme disease spirochete isolates and aligned these with 8 sequences previously presented. The 16S rRNA signature nucleotide compositions were defined for each isolate and compared with the genomic species signature nucleotide sets previously established. To identify positions truly indicative of species classification which could serve as targets for polymerase chain reaction species-specific identification primers, 16S rRNA-based phylogenetic analyses were conducted. On the basis of the identified signature nucleotides, we designed polymerase chain reaction primer sets which (i) amplify all spirochete species associated with Lyme disease and (ii) differentiate between these species. The primer sets were tested on 38 Borrelia isolates associated with Lyme disease and were found to be sensitive and specific. All Lyme disease isolates tested were amplification positive. These primers allow for the rapid species identification of Lyme disease isolates."} {"id": "PMID:1280644", "title": "Identification of a genetically distinct subspecies of Mycobacterium kansasii.", "content": "To assess the usefulness of a specific DNA probe for Mycobacterium kansasii, 105 isolates from Australia, Belgium, Japan, South Africa, and Switzerland were collected and analyzed. Twenty of these isolates were probe negative, of which 18 were from Belgium and Switzerland. Analysis of all isolates by Southern blot hybridization indicated a lack of variability among probe-positive isolates, while probe-negative isolates were clearly distinct and showed greater diversity. Sequence analysis of the 250 nucleotides at the 5' end of the 16S rRNA gene revealed that 19 of the 20 probe-negative isolates had a sequence different from that of M. kansasii. A total of five nucleotide differences were present in a cluster consisting of two nucleotide deletions and three nucleotide substitutions. These results suggest the existence of a genetic subspecies of M. kansasii.", "contents": "Identification of a genetically distinct subspecies of Mycobacterium kansasii. To assess the usefulness of a specific DNA probe for Mycobacterium kansasii, 105 isolates from Australia, Belgium, Japan, South Africa, and Switzerland were collected and analyzed. Twenty of these isolates were probe negative, of which 18 were from Belgium and Switzerland. Analysis of all isolates by Southern blot hybridization indicated a lack of variability among probe-positive isolates, while probe-negative isolates were clearly distinct and showed greater diversity. Sequence analysis of the 250 nucleotides at the 5' end of the 16S rRNA gene revealed that 19 of the 20 probe-negative isolates had a sequence different from that of M. kansasii. A total of five nucleotide differences were present in a cluster consisting of two nucleotide deletions and three nucleotide substitutions. These results suggest the existence of a genetic subspecies of M. kansasii."} {"id": "PMID:1280645", "title": "Isolation of a fastidious Mycobacterium species from two AIDS patients.", "content": "Two strains of fastidious mycobacteria were isolated from two patients with AIDS and clinical disease suggestive of Mycobacterium avium complex infection. Acid-fast bacilli were isolated from blood and bone marrow of both patients in BACTEC 12B and/or 13A media. The acid-fast bacilli failed to grow on subculture to routine L\u00f6wenstein-Jensen medium containing pyruvate and egg yolk agar. After several attempts, the strain from one patient was finally cultured on Middlebrook 7H9 medium with agar, charcoal, and yeast extract 13 months after the initial specimens were received in the laboratory. The second patient's strain was cultured on the same medium 6 weeks postinoculation with fresh BACTEC fluid and 5 months after specimen collection. Routine biochemical and growth tests were performed on these isolates but failed to give definitive identifications. 16S rRNA gene sequencing suggested that the organisms share at least 98.9% homology with M. simiae. Even greater homology (99.86%) was found with the recently described species \"M. genavense.\" Recognition of the fastidious nature of some mycobacteria that infect AIDS patients is important in the treatment of infections in these patients and in understanding the epidemiology of atypical mycobacterial infections. It is suggested that a liquid culture medium such as BACTEC be employed for primary isolation of mycobacteria from AIDS patients and that subculture to the charcoal medium described here be carried out for those organisms that fail to grow on subculture to routine media.", "contents": "Isolation of a fastidious Mycobacterium species from two AIDS patients. Two strains of fastidious mycobacteria were isolated from two patients with AIDS and clinical disease suggestive of Mycobacterium avium complex infection. Acid-fast bacilli were isolated from blood and bone marrow of both patients in BACTEC 12B and/or 13A media. The acid-fast bacilli failed to grow on subculture to routine L\u00f6wenstein-Jensen medium containing pyruvate and egg yolk agar. After several attempts, the strain from one patient was finally cultured on Middlebrook 7H9 medium with agar, charcoal, and yeast extract 13 months after the initial specimens were received in the laboratory. The second patient's strain was cultured on the same medium 6 weeks postinoculation with fresh BACTEC fluid and 5 months after specimen collection. Routine biochemical and growth tests were performed on these isolates but failed to give definitive identifications. 16S rRNA gene sequencing suggested that the organisms share at least 98.9% homology with M. simiae. Even greater homology (99.86%) was found with the recently described species \"M. genavense.\" Recognition of the fastidious nature of some mycobacteria that infect AIDS patients is important in the treatment of infections in these patients and in understanding the epidemiology of atypical mycobacterial infections. It is suggested that a liquid culture medium such as BACTEC be employed for primary isolation of mycobacteria from AIDS patients and that subculture to the charcoal medium described here be carried out for those organisms that fail to grow on subculture to routine media."} {"id": "PMID:1280646", "title": "Molecular characterization of Serpulina (Treponema) hyodysenteriae isolates representing serotypes 8 and 9.", "content": "The study described here was carried out to further characterize reference strains of Serpulina (Treponema) hyodysenteriae representing serotypes 8 and 9. Results obtained from restriction fragment length polymorphism analysis, enteropathogenicity testing, and endotoxin profiles confirmed their identifications. Electron microscopy indicated that both strains were covered with a thin layer of capsule-like material. Immunoblot analysis indicated that an antigen in the 19-kDa region of proteinase K-digested whole cells reacted only with homologous antiserum. The serotype-specific antigens were sensitive to periodate oxidation but resistant to proteinase K digestion and migrated in the same region as purified lipopolysaccharides. Immunoblotting with proteinase K-digested whole cells appeared as useful as immunodiffusion with extracted lipopolysaccharide for the serological classification of S. hyodysenteriae. Immunogold labeling of whole cells and purified periplasmic flagella showed strong cross-reactions between S. hyodysenteriae and Serpulina innocens. Outer membrane preparations of strains representing serotypes 8 and 9 contained four major proteins which reacted with antisera against both species, and one major protein with a molecular mass of 46 kDa which reacted only with antisera against S. hyodysenteriae, irrespective of the serotype. Our findings suggest that periplasmic flagella and some outer membrane proteins are antigens common to both S. hyodysenteriae and S. innocens, whereas a 46-kDa outer membrane protein may be a species-specific antigen of S. hyodysenteriae. Finally, we propose immunoblotting as an alternative method to immunodiffusion for the serotyping of S. hyodysenteriae.", "contents": "Molecular characterization of Serpulina (Treponema) hyodysenteriae isolates representing serotypes 8 and 9. The study described here was carried out to further characterize reference strains of Serpulina (Treponema) hyodysenteriae representing serotypes 8 and 9. Results obtained from restriction fragment length polymorphism analysis, enteropathogenicity testing, and endotoxin profiles confirmed their identifications. Electron microscopy indicated that both strains were covered with a thin layer of capsule-like material. Immunoblot analysis indicated that an antigen in the 19-kDa region of proteinase K-digested whole cells reacted only with homologous antiserum. The serotype-specific antigens were sensitive to periodate oxidation but resistant to proteinase K digestion and migrated in the same region as purified lipopolysaccharides. Immunoblotting with proteinase K-digested whole cells appeared as useful as immunodiffusion with extracted lipopolysaccharide for the serological classification of S. hyodysenteriae. Immunogold labeling of whole cells and purified periplasmic flagella showed strong cross-reactions between S. hyodysenteriae and Serpulina innocens. Outer membrane preparations of strains representing serotypes 8 and 9 contained four major proteins which reacted with antisera against both species, and one major protein with a molecular mass of 46 kDa which reacted only with antisera against S. hyodysenteriae, irrespective of the serotype. Our findings suggest that periplasmic flagella and some outer membrane proteins are antigens common to both S. hyodysenteriae and S. innocens, whereas a 46-kDa outer membrane protein may be a species-specific antigen of S. hyodysenteriae. Finally, we propose immunoblotting as an alternative method to immunodiffusion for the serotyping of S. hyodysenteriae."} {"id": "PMID:1280647", "title": "Differentiation of Shigella flexneri strains by rRNA gene restriction patterns.", "content": "We studied the restriction endonuclease cleavage patterns of rRNA genes (ribotypes) of 72 clinical isolates of Shigella flexneri representing eight serotypes to determine whether ribotyping could be used to distinguish S. flexneri strains and to compare the discriminating ability of the method with that of serotyping. By using a cloned Escherichia coli rRNA operon as the probe, Southern blot hybridization of restriction endonuclease-digested total DNA was carried out. Ribotyping of the isolates with each of the five restriction endonucleases BamHI, EcoRI, HindIII, PstI, and SalI generated reproducible restriction patterns. However, HindIII produced the optimum digestion pattern of the rRNA genes and was more useful than the other enzymes used in differentiating strains. Analysis of the 72 isolates showed 11 different HindIII cleavage patterns of their rRNA genes. Four of these HindIII-generated ribotypes could be further differentiated into two to four subribotypes by using PstI. The results indicate that ribotyping has an application for differentiation of S. flexneri strains and can complement serotyping. Definition of strains in terms of both serotype and ribotype may be of greater use in epidemiological studies.", "contents": "Differentiation of Shigella flexneri strains by rRNA gene restriction patterns. We studied the restriction endonuclease cleavage patterns of rRNA genes (ribotypes) of 72 clinical isolates of Shigella flexneri representing eight serotypes to determine whether ribotyping could be used to distinguish S. flexneri strains and to compare the discriminating ability of the method with that of serotyping. By using a cloned Escherichia coli rRNA operon as the probe, Southern blot hybridization of restriction endonuclease-digested total DNA was carried out. Ribotyping of the isolates with each of the five restriction endonucleases BamHI, EcoRI, HindIII, PstI, and SalI generated reproducible restriction patterns. However, HindIII produced the optimum digestion pattern of the rRNA genes and was more useful than the other enzymes used in differentiating strains. Analysis of the 72 isolates showed 11 different HindIII cleavage patterns of their rRNA genes. Four of these HindIII-generated ribotypes could be further differentiated into two to four subribotypes by using PstI. The results indicate that ribotyping has an application for differentiation of S. flexneri strains and can complement serotyping. Definition of strains in terms of both serotype and ribotype may be of greater use in epidemiological studies."} {"id": "PMID:1280648", "title": "Antibody to a recombinant merozoite protein epitope identifies horses infected with Babesia equi.", "content": "Horses infected with Babesia equi were previously identified by the presence of antibodies reactive with a merozoite surface protein epitope (D. P. Knowles, Jr., L. E. Perryman, L. S. Kappmeyer, and S. G. Hennager. J. Clin. Microbiol. 29:2056-2058, 1991). The antibodies were detected in a competitive inhibition enzyme-linked immunosorbent assay (CI ELISA) by using monoclonal antibody 36/133.97, which defines a protein epitope on the merozoite surface. The gene encoding this B. equi merozoite epitope was cloned and expressed in Escherichia coli. The recombinant merozoite protein, designated equi merozoite antigen 1 (EMA-1), was evaluated in the CI ELISA. Recombinant EMA-1 bound antibody from the sera of B. equi-infected horses from 18 countries. The antibody response to EMA-1 was then measured in horses experimentally infected with B. equi via transmission by the tick vector Boophilus microplus or by intravenous inoculation. Anti-EMA-1 antibody was detected 7 weeks post-tick exposure and remained, without reexposure to B. equi, for the 33 weeks of the evaluation period. The data indicate that recombinant EMA-1 can be used in the CI ELISA to detect horses infected with B. equi.", "contents": "Antibody to a recombinant merozoite protein epitope identifies horses infected with Babesia equi. Horses infected with Babesia equi were previously identified by the presence of antibodies reactive with a merozoite surface protein epitope (D. P. Knowles, Jr., L. E. Perryman, L. S. Kappmeyer, and S. G. Hennager. J. Clin. Microbiol. 29:2056-2058, 1991). The antibodies were detected in a competitive inhibition enzyme-linked immunosorbent assay (CI ELISA) by using monoclonal antibody 36/133.97, which defines a protein epitope on the merozoite surface. The gene encoding this B. equi merozoite epitope was cloned and expressed in Escherichia coli. The recombinant merozoite protein, designated equi merozoite antigen 1 (EMA-1), was evaluated in the CI ELISA. Recombinant EMA-1 bound antibody from the sera of B. equi-infected horses from 18 countries. The antibody response to EMA-1 was then measured in horses experimentally infected with B. equi via transmission by the tick vector Boophilus microplus or by intravenous inoculation. Anti-EMA-1 antibody was detected 7 weeks post-tick exposure and remained, without reexposure to B. equi, for the 33 weeks of the evaluation period. The data indicate that recombinant EMA-1 can be used in the CI ELISA to detect horses infected with B. equi."} {"id": "PMID:1280649", "title": "Detection of Norwalk virus in stool specimens by reverse transcriptase-polymerase chain reaction and nonradioactive oligoprobes.", "content": "A reverse transcriptase (RT)-polymerase chain reaction (PCR)-oligoprobe (OP), or RT-PCR-OP, method was developed for the detection of the Norwalk virus, which causes acute, epidemic gastroenteritis, in stool specimens. The Norwalk virus genome regions encoding the following two proteins were amplified by RT-PCR: the RNA polymerase (260-bp product) and a putative immunogenic protein (224-bp product). The resulting DNA fragments (amplicons) were hybridized to a digoxigenin-labeled internal OP specific to each amplicon. The detection limit of Norwalk virus, as determined by the endpoint of RT-PCR amplification for serially diluted, positive stool specimens, was similar to the actual virion titer as estimated by electron microscopy and at least 100-fold greater than the titer determined by radioimmunoassay (RIA). The RT-PCR-OP assay was specific for Norwalk virus and negative for other enteric viruses, including human and animal caliciviruses, hepatitis E virus, Snow Mountain agent, astroviruses, 16 human enteroviruses, and 5 human rotaviruses. Components of fecal specimens that interfere with RT-PCR were removed successfully by Sephadex G-200 gel chromatography. Of 20 stool specimens from human volunteers that were positive for Norwalk virus by RIA, a specific RT-PCR-OP result was obtained in 95% (19 of 20) of the samples by using the immunogenic protein primers and 75% (15 of 20) by using the polymerase primers. Twenty-six stool specimens from asymptomatic children and adults were negative by the Norwalk virus RT-PCR-OP. RT-PCR-OP detected Norwalk virus in the 4 of 21 coded fecal specimens that were also positive by enzyme immunoassay. Two samples that were positive by RIA or enzyme immunoassay were negative by RT-PCR, perhaps because viral RNA was not present or RT-PCR inhibitors were not adequately removed.", "contents": "Detection of Norwalk virus in stool specimens by reverse transcriptase-polymerase chain reaction and nonradioactive oligoprobes. A reverse transcriptase (RT)-polymerase chain reaction (PCR)-oligoprobe (OP), or RT-PCR-OP, method was developed for the detection of the Norwalk virus, which causes acute, epidemic gastroenteritis, in stool specimens. The Norwalk virus genome regions encoding the following two proteins were amplified by RT-PCR: the RNA polymerase (260-bp product) and a putative immunogenic protein (224-bp product). The resulting DNA fragments (amplicons) were hybridized to a digoxigenin-labeled internal OP specific to each amplicon. The detection limit of Norwalk virus, as determined by the endpoint of RT-PCR amplification for serially diluted, positive stool specimens, was similar to the actual virion titer as estimated by electron microscopy and at least 100-fold greater than the titer determined by radioimmunoassay (RIA). The RT-PCR-OP assay was specific for Norwalk virus and negative for other enteric viruses, including human and animal caliciviruses, hepatitis E virus, Snow Mountain agent, astroviruses, 16 human enteroviruses, and 5 human rotaviruses. Components of fecal specimens that interfere with RT-PCR were removed successfully by Sephadex G-200 gel chromatography. Of 20 stool specimens from human volunteers that were positive for Norwalk virus by RIA, a specific RT-PCR-OP result was obtained in 95% (19 of 20) of the samples by using the immunogenic protein primers and 75% (15 of 20) by using the polymerase primers. Twenty-six stool specimens from asymptomatic children and adults were negative by the Norwalk virus RT-PCR-OP. RT-PCR-OP detected Norwalk virus in the 4 of 21 coded fecal specimens that were also positive by enzyme immunoassay. Two samples that were positive by RIA or enzyme immunoassay were negative by RT-PCR, perhaps because viral RNA was not present or RT-PCR inhibitors were not adequately removed."} {"id": "PMID:1280650", "title": "Comparison of whole-cell antibodies and an antigenic flagellar epitope of Borrelia burgdorferi in serologic tests for diagnosis of Lyme borreliosis.", "content": "A recombinant protein (p41-G) of an antigenic region of flagellin was used in a standard and amplified enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Borrelia burgdorferi, the causative agent of Lyme borreliosis. Comparable sensitivities (88 to 94%) were noted when sera from 17 persons who had erythema migrans and antibodies to whole-cell B. burgdorferi were tested against the p41-G antigen. In tests of a second study group of 36 persons who had erythema migrans but no detectable antibodies to whole-cell B. burgdorferi, 3 (8%) were positive when the p41-G antigen was used. Assay specificity likewise increased when the p41-G fragment was included in an ELISA with human sera containing treponemal antibodies. Recombinant flagellar proteins of B. burgdorferi, such as the p41-G antigen, can be used in an ELISA and may help confirm Lyme borreliosis during early stages of infection and improve specificity.", "contents": "Comparison of whole-cell antibodies and an antigenic flagellar epitope of Borrelia burgdorferi in serologic tests for diagnosis of Lyme borreliosis. A recombinant protein (p41-G) of an antigenic region of flagellin was used in a standard and amplified enzyme-linked immunosorbent assay (ELISA) to detect antibodies to Borrelia burgdorferi, the causative agent of Lyme borreliosis. Comparable sensitivities (88 to 94%) were noted when sera from 17 persons who had erythema migrans and antibodies to whole-cell B. burgdorferi were tested against the p41-G antigen. In tests of a second study group of 36 persons who had erythema migrans but no detectable antibodies to whole-cell B. burgdorferi, 3 (8%) were positive when the p41-G antigen was used. Assay specificity likewise increased when the p41-G fragment was included in an ELISA with human sera containing treponemal antibodies. Recombinant flagellar proteins of B. burgdorferi, such as the p41-G antigen, can be used in an ELISA and may help confirm Lyme borreliosis during early stages of infection and improve specificity."} {"id": "PMID:1280651", "title": "Antigenicity of Helicobacter pylori lipopolysaccharides.", "content": "An investigation of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) profiles of lipopolysaccharides (LPSs) extracted from seven strains of Helicobacter pylori revealed that these molecules were silver stainable and exhibited a high degree of variability in their patterns. Two strains synthesized a variety of sizes of LPS molecules such that fractionation by SDS-PAGE resulted in a stepwise gradation of bands which extended from the top to the bottom of the silver-stained gel. The LPSs from the remaining five strains were made up of molecules which were more homogeneous in size and clustered around two separate areas of the gel. Antigenic analyses of phenol-water-extracted LPSs by immunoblotting and the passive hemagglutination assay suggested that, in addition to strain-specific antigens, all of the LPSs carried a common antigen. Antibodies to this common antigen could be removed from antisera by absorption, and the resulting antisera were used to differentiate strains on the basis of their O antigens by the passive hemagglutination assay technique. The finding that LPSs from 3 of 10 clinical isolates reacted specifically in one or two of the typing antisera suggested that the development of a scheme for differentiating H. pylori on the basis of O antigens is feasible.", "contents": "Antigenicity of Helicobacter pylori lipopolysaccharides. An investigation of the sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) profiles of lipopolysaccharides (LPSs) extracted from seven strains of Helicobacter pylori revealed that these molecules were silver stainable and exhibited a high degree of variability in their patterns. Two strains synthesized a variety of sizes of LPS molecules such that fractionation by SDS-PAGE resulted in a stepwise gradation of bands which extended from the top to the bottom of the silver-stained gel. The LPSs from the remaining five strains were made up of molecules which were more homogeneous in size and clustered around two separate areas of the gel. Antigenic analyses of phenol-water-extracted LPSs by immunoblotting and the passive hemagglutination assay suggested that, in addition to strain-specific antigens, all of the LPSs carried a common antigen. Antibodies to this common antigen could be removed from antisera by absorption, and the resulting antisera were used to differentiate strains on the basis of their O antigens by the passive hemagglutination assay technique. The finding that LPSs from 3 of 10 clinical isolates reacted specifically in one or two of the typing antisera suggested that the development of a scheme for differentiating H. pylori on the basis of O antigens is feasible."} {"id": "PMID:1280652", "title": "Laboratory aspects of \"Mycobacterium genavense,\" a proposed species isolated from AIDS patients.", "content": "\"Mycobacterium genavense\" is a proposed new species recently reported to cause disseminated infections in 18 patients with AIDS in Europe. We have recovered \"M. genavense\" as slowly growing fastidious mycobacteria in blood cultures of seven patients with AIDS. In the original studies of \"M. genavense,\" the fastidious organism grew only in BACTEC 13A vials. The Seattle, Washington, isolates of \"M. genavense\" also failed to grow when subcultured from 13A vials to routine solid media, but dysgonic colonies were produced on Middlebrook 7H11 agar supplemented with mycobactin J. The mycolic acid pattern of patients' isolates closely resembled that of the type strain of Mycobacterium simiae when analyzed by one- and two-dimensional thin-layer chromatography and by high-performance liquid chromatography. Whole-cell fatty acid analyses by gas-liquid chromatography distinguished the isolates from M. simiae but misidentified them as Mycobacterium fortuitum. Sequence determinations of the hypervariable regions of the 16S rRNA gene indicate that these organisms belong to the recently proposed new species \"M. genavense.\" Growth from Middlebrook 7H11 agar supplemented with mycobactin J consistently yielded positive tests for catalase (semiquantitative and at 68 degrees C), pyrazinamidase, and urease which enable mycobacteriology laboratories to presumptively identify \"M. genavense\" without nucleic acid analyses. The failure of \"M. genavense\" to grow on conventional mycobacterial solid media suggests that mycobacterial blood cultures should include a broth medium incubated for at least 8 weeks.", "contents": "Laboratory aspects of \"Mycobacterium genavense,\" a proposed species isolated from AIDS patients. \"Mycobacterium genavense\" is a proposed new species recently reported to cause disseminated infections in 18 patients with AIDS in Europe. We have recovered \"M. genavense\" as slowly growing fastidious mycobacteria in blood cultures of seven patients with AIDS. In the original studies of \"M. genavense,\" the fastidious organism grew only in BACTEC 13A vials. The Seattle, Washington, isolates of \"M. genavense\" also failed to grow when subcultured from 13A vials to routine solid media, but dysgonic colonies were produced on Middlebrook 7H11 agar supplemented with mycobactin J. The mycolic acid pattern of patients' isolates closely resembled that of the type strain of Mycobacterium simiae when analyzed by one- and two-dimensional thin-layer chromatography and by high-performance liquid chromatography. Whole-cell fatty acid analyses by gas-liquid chromatography distinguished the isolates from M. simiae but misidentified them as Mycobacterium fortuitum. Sequence determinations of the hypervariable regions of the 16S rRNA gene indicate that these organisms belong to the recently proposed new species \"M. genavense.\" Growth from Middlebrook 7H11 agar supplemented with mycobactin J consistently yielded positive tests for catalase (semiquantitative and at 68 degrees C), pyrazinamidase, and urease which enable mycobacteriology laboratories to presumptively identify \"M. genavense\" without nucleic acid analyses. The failure of \"M. genavense\" to grow on conventional mycobacterial solid media suggests that mycobacterial blood cultures should include a broth medium incubated for at least 8 weeks."} {"id": "PMID:1280653", "title": "Purification of Pneumocystis carinii trophozoites and identification of their circulating antigens.", "content": "We have developed a new method to isolate Pneumocystis carinii trophozoites from experimental rat bronchoalveolar lavage specimens by using a Percoll discontinuous gradient and have identified the circulating antigens in experimental rat P. carinii pneumonia. The antigenic components of the trophozoites were compared with those of cysts by immunoblotting. A major immunoreactive band of 90,000 Da and some others of lower molecular mass were found in trophozoites. On the other hand, bands of 110,000, 50,000, and 45,000 Da were observed in cysts. The band of 50,000 Da was not identified when antitrophozoite rabbit serum preabsorbed with P. carinii-infected rat serum was used for immunoblotting. These results suggest that the molecule of 50,000 Da is the major circulating antigen in P. carinii-infected rats.", "contents": "Purification of Pneumocystis carinii trophozoites and identification of their circulating antigens. We have developed a new method to isolate Pneumocystis carinii trophozoites from experimental rat bronchoalveolar lavage specimens by using a Percoll discontinuous gradient and have identified the circulating antigens in experimental rat P. carinii pneumonia. The antigenic components of the trophozoites were compared with those of cysts by immunoblotting. A major immunoreactive band of 90,000 Da and some others of lower molecular mass were found in trophozoites. On the other hand, bands of 110,000, 50,000, and 45,000 Da were observed in cysts. The band of 50,000 Da was not identified when antitrophozoite rabbit serum preabsorbed with P. carinii-infected rat serum was used for immunoblotting. These results suggest that the molecule of 50,000 Da is the major circulating antigen in P. carinii-infected rats."} {"id": "PMID:1280654", "title": "CD43 expression in B cell lymphoma.", "content": "To determine the expression of CD43 in frozen sections in a range of B cell lymphomas. The monoclonal antibody WR14, clustered provisionally in the Fourth Leucocyte Typing Workshop as a CD43 reagent, was investigated by epitope blocking studies on formalin fixed reactive lymph node tissue, using the established CD43 antibody MT1, to validate its use as a CD43 reagent. CD43 expression was studied in 131 immunophenotypically defined B cell lymphomas, including lymphocytic lymphoma (Lc, n = 13), centrocytic lymphoma (Cc, n = 14), and a range of follicle centre cell lymphomas (FCC) including centroblastic/centrocytic follicular (CbCcF, n = 48), centroblastic diffuse (CbD, n = 39), centroblastic/centrocytic diffuse (CbCcD, n = 4), centroblastic follicular and diffuse (Cb FD, n = 3) and centroblastic/centrocytic follicular and diffuse (CbCc FD, n = 1). Nine lymphomas of mucosa associated lymphoid tissue (MALT) were also examined. Epitope blocking studies showed that WR14 is a CD43 reagent that binds to an epitope identical with or close to that recognised by MT1. Eleven of 13 (84%) cases of Lc and 11 of 14 (78%) cases of Cc expressed CD43; 87 of 95 (91%) cases of FCC did not. All eight low grade lymphomas of MALT were negative. One high grade lymphoma, transformed from a low grade MALT lymphoma, was positive for CD43. The expression of CD43 by tumours of B cell lineage was associated with the expression of CD5 (p < 0.001) although either antigen could occasionally be found in the absence of the other. CD43 reagents can be used in conjunction with CD5 antibodies for the immunophenotypic discrimination of follicle centre cell lymphomas from non-follicle centre cell lymphomas.", "contents": "CD43 expression in B cell lymphoma. To determine the expression of CD43 in frozen sections in a range of B cell lymphomas. The monoclonal antibody WR14, clustered provisionally in the Fourth Leucocyte Typing Workshop as a CD43 reagent, was investigated by epitope blocking studies on formalin fixed reactive lymph node tissue, using the established CD43 antibody MT1, to validate its use as a CD43 reagent. CD43 expression was studied in 131 immunophenotypically defined B cell lymphomas, including lymphocytic lymphoma (Lc, n = 13), centrocytic lymphoma (Cc, n = 14), and a range of follicle centre cell lymphomas (FCC) including centroblastic/centrocytic follicular (CbCcF, n = 48), centroblastic diffuse (CbD, n = 39), centroblastic/centrocytic diffuse (CbCcD, n = 4), centroblastic follicular and diffuse (Cb FD, n = 3) and centroblastic/centrocytic follicular and diffuse (CbCc FD, n = 1). Nine lymphomas of mucosa associated lymphoid tissue (MALT) were also examined. Epitope blocking studies showed that WR14 is a CD43 reagent that binds to an epitope identical with or close to that recognised by MT1. Eleven of 13 (84%) cases of Lc and 11 of 14 (78%) cases of Cc expressed CD43; 87 of 95 (91%) cases of FCC did not. All eight low grade lymphomas of MALT were negative. One high grade lymphoma, transformed from a low grade MALT lymphoma, was positive for CD43. The expression of CD43 by tumours of B cell lineage was associated with the expression of CD5 (p < 0.001) although either antigen could occasionally be found in the absence of the other. CD43 reagents can be used in conjunction with CD5 antibodies for the immunophenotypic discrimination of follicle centre cell lymphomas from non-follicle centre cell lymphomas."} {"id": "PMID:1280655", "title": "Neurogenic inflammation and the oral mucosa.", "content": "Since the r\u00f4le of neurogenic inflammation in various pathological conditions is well-established, we presume that it also has great importance in the development of several inflammatory processes in the oral mucosa. In the course of experimentally-induced neurogenic inflammation of the oral mucosa in rats, vasodilation and plasma extravasation occur in the area supplied by unmyelinated capsaicin-sensitive fibres. Upon activating these fibres in the oral mucosa, mediators such as histamine, substance P (SP) and calcitonin gene related peptide (CGRP) are released from the peripheral terminals of afferent nerves causing characteristic symptoms of neurogenic inflammation. By histochemical techniques, SP- and CGRP-immunoreactive fibres have occurred in the area of the rat oral mucosa stimulated mostly in the free and attached gingiva around the molar teeth in the lower jaw. Capsaicin pretreatment performed neonatally or at adult age causes a loss of SP-immunoreactive fibres and prevents the vasodilatory responses, as well as the increase in vascular permeability elicited by the antidromic stimulation of the inferior alveolar nerve. As the transection of inferior alveolar nerve decreased the extravasation of Evans blue on the ipsilateral side and did not affect the capsaicin-induced enhancement in blood flow, we suggest that the two symptoms of the inflammation, i.e., the increased vascular permeability and decreased vascular resistance, should be produced by different mechanisms. The results of all the morphological and functional studies seem to confirm the possibility that there is an important neurogenic component of the inflammatory alterations caused by different mechanical and chemical stimuli in the oral mucosa.", "contents": "Neurogenic inflammation and the oral mucosa. Since the r\u00f4le of neurogenic inflammation in various pathological conditions is well-established, we presume that it also has great importance in the development of several inflammatory processes in the oral mucosa. In the course of experimentally-induced neurogenic inflammation of the oral mucosa in rats, vasodilation and plasma extravasation occur in the area supplied by unmyelinated capsaicin-sensitive fibres. Upon activating these fibres in the oral mucosa, mediators such as histamine, substance P (SP) and calcitonin gene related peptide (CGRP) are released from the peripheral terminals of afferent nerves causing characteristic symptoms of neurogenic inflammation. By histochemical techniques, SP- and CGRP-immunoreactive fibres have occurred in the area of the rat oral mucosa stimulated mostly in the free and attached gingiva around the molar teeth in the lower jaw. Capsaicin pretreatment performed neonatally or at adult age causes a loss of SP-immunoreactive fibres and prevents the vasodilatory responses, as well as the increase in vascular permeability elicited by the antidromic stimulation of the inferior alveolar nerve. As the transection of inferior alveolar nerve decreased the extravasation of Evans blue on the ipsilateral side and did not affect the capsaicin-induced enhancement in blood flow, we suggest that the two symptoms of the inflammation, i.e., the increased vascular permeability and decreased vascular resistance, should be produced by different mechanisms. The results of all the morphological and functional studies seem to confirm the possibility that there is an important neurogenic component of the inflammatory alterations caused by different mechanical and chemical stimuli in the oral mucosa."} {"id": "PMID:1280656", "title": "Characteristics of ruminant mammary epithelial cells grown in primary culture in serum-free medium.", "content": "Cells were obtained from the mammary glands of sheep and cows by collagenase-hyaluronidase digestion. Characterization of cells as epithelial was by reaction with a monoclonal antibody to cytokeratin. A subpopulation of spindle-shaped or stellate cells reacted with a monoclonal antibody to desmin and may be related to myoepithelial cells. The development is described of a simple serum-free culture system for these cells on gels of rat tail (type 1) collagen. A commercial medium (M199) was used, buffered with Hepes and with bovine serum albumin as the sole protein supplement, plus fibronectin for the first 18 h only as an attachment factor. The cell cultures showed stimulated DNA synthesis in response to mitogens on attached gels and also responded as floating cultures to lactogenic hormones with production of alpha-lactalbumin.", "contents": "Characteristics of ruminant mammary epithelial cells grown in primary culture in serum-free medium. Cells were obtained from the mammary glands of sheep and cows by collagenase-hyaluronidase digestion. Characterization of cells as epithelial was by reaction with a monoclonal antibody to cytokeratin. A subpopulation of spindle-shaped or stellate cells reacted with a monoclonal antibody to desmin and may be related to myoepithelial cells. The development is described of a simple serum-free culture system for these cells on gels of rat tail (type 1) collagen. A commercial medium (M199) was used, buffered with Hepes and with bovine serum albumin as the sole protein supplement, plus fibronectin for the first 18 h only as an attachment factor. The cell cultures showed stimulated DNA synthesis in response to mitogens on attached gels and also responded as floating cultures to lactogenic hormones with production of alpha-lactalbumin."} {"id": "PMID:1280657", "title": "'Usage' testing of root canal sealing materials--a personal view.", "content": "A number of systems for the biological testing of dental materials have been suggested. This paper reviews the protocols suggested in the ISO standards for the in-use or 'usage' tests for root canal sealing materials.", "contents": "'Usage' testing of root canal sealing materials--a personal view. A number of systems for the biological testing of dental materials have been suggested. This paper reviews the protocols suggested in the ISO standards for the in-use or 'usage' tests for root canal sealing materials."} {"id": "PMID:1280658", "title": "A comparison of four in vitro marginal leakage tests applied to root surface restorations.", "content": "Marginal leakage associated with a variety of restorative materials, placed in root surface cavities of extracted teeth, was assessed by immersing the teeth in either acidified gelatin, eosin dye, silver nitrate or a solution of radiocalcium. The allocation of a score, dependent on the depth of tracer penetration at the interface, allowed comparisons to be made between the leakage tests employed. The rank order of the four leakage tests was generally consistent. Eosin resulted in the most severe leakage, followed by silver nitrate and radiocalcium, whilst acidified gelatin was the least sensitive method for demonstrating marginal leakage. Differences in leakage scores were not, however, always statistically significant. None of the four tests investigated was ideal, although eosin dye was considered to be the most appropriate method of demonstrating marginal leakage associated with root restorations.", "contents": "A comparison of four in vitro marginal leakage tests applied to root surface restorations. Marginal leakage associated with a variety of restorative materials, placed in root surface cavities of extracted teeth, was assessed by immersing the teeth in either acidified gelatin, eosin dye, silver nitrate or a solution of radiocalcium. The allocation of a score, dependent on the depth of tracer penetration at the interface, allowed comparisons to be made between the leakage tests employed. The rank order of the four leakage tests was generally consistent. Eosin resulted in the most severe leakage, followed by silver nitrate and radiocalcium, whilst acidified gelatin was the least sensitive method for demonstrating marginal leakage. Differences in leakage scores were not, however, always statistically significant. None of the four tests investigated was ideal, although eosin dye was considered to be the most appropriate method of demonstrating marginal leakage associated with root restorations."} {"id": "PMID:1280660", "title": "Canine left ventricular hypertrophy predisposes to ventricular tachycardia induction by phase 2 early afterdepolarizations after administration of BAY K 8644.", "content": "The purpose of this study was to test the hypothesis that the longer duration of ventricular action potentials in hypertrophied hearts predisposes to the development of early after-depolarizations and triggered ventricular tachyarrhythmias. For unknown reasons, the incidence of sudden death is greater in patients with myocardial hypertrophy. We measured left ventricular monophasic action potentials in normal dogs and dogs with left ventricular hypertrophy before and after administration of the calcium agonist BAY K 8644 and the potassium channel blocker cesium. We demonstrated longer action potential durations in dogs with than in those without left ventricular hypertrophy. Also, BAY K 8644 produced phase 2 early afterdepolarizations and ventricular tachyarrhythmias more frequently in the dogs with than in those without left ventricular hypertrophy. Phenylephrine, an alpha agonist, further increased the action potential duration in hypertrophied hearts and the propensity to develop early afterdepolarizations and ventricular tachyarrhythmia after administration of BAY K 8644. Control and hypertrophied hearts developed early afterdepolarizations and ventricular tachyarrhythmia equally when exposed to cesium. Although in vitro studies have shown that fibers of hypertrophied ventricular myocardium can develop triggered activity as a result of both early and late afterdepolarizations, the present study is the first to show in vivo that the hypertrophied ventricular myocardium compared with the normal ventricle is predisposed to develop phase 2 early afterdepolarizations that appear to trigger ventricular tachyarrhythmia. It is possible that such a mechanism contributes to the development of ventricular tachyarrhythmia and sudden cardiac death in patients with left ventricular hypertrophy. If this is shown to be true, specific pharmacologic interventions can be suggested.", "contents": "Canine left ventricular hypertrophy predisposes to ventricular tachycardia induction by phase 2 early afterdepolarizations after administration of BAY K 8644. The purpose of this study was to test the hypothesis that the longer duration of ventricular action potentials in hypertrophied hearts predisposes to the development of early after-depolarizations and triggered ventricular tachyarrhythmias. For unknown reasons, the incidence of sudden death is greater in patients with myocardial hypertrophy. We measured left ventricular monophasic action potentials in normal dogs and dogs with left ventricular hypertrophy before and after administration of the calcium agonist BAY K 8644 and the potassium channel blocker cesium. We demonstrated longer action potential durations in dogs with than in those without left ventricular hypertrophy. Also, BAY K 8644 produced phase 2 early afterdepolarizations and ventricular tachyarrhythmias more frequently in the dogs with than in those without left ventricular hypertrophy. Phenylephrine, an alpha agonist, further increased the action potential duration in hypertrophied hearts and the propensity to develop early afterdepolarizations and ventricular tachyarrhythmia after administration of BAY K 8644. Control and hypertrophied hearts developed early afterdepolarizations and ventricular tachyarrhythmia equally when exposed to cesium. Although in vitro studies have shown that fibers of hypertrophied ventricular myocardium can develop triggered activity as a result of both early and late afterdepolarizations, the present study is the first to show in vivo that the hypertrophied ventricular myocardium compared with the normal ventricle is predisposed to develop phase 2 early afterdepolarizations that appear to trigger ventricular tachyarrhythmia. It is possible that such a mechanism contributes to the development of ventricular tachyarrhythmia and sudden cardiac death in patients with left ventricular hypertrophy. If this is shown to be true, specific pharmacologic interventions can be suggested."} {"id": "PMID:1280661", "title": "Chick embryo exposure to carbamates alters neurochemical parameters and behavior.", "content": "Recent evidence has shown that exposure to pesticides can lead to long-term neurophysiological and functional deficits. We have demonstrated previously that locomotion in chicks exposed to some organophosphates and carbamates could be altered persistently without concomitant central or peripheral esterase inhibition. Furthermore, histopathology of the ataxic chickens showed no lesions in either the central or peripheral systems. In this study, we examined whether locomotion alterations seen in chicks exposed in ovo to carbaryl and aldicarb are accompanied by perturbations in particular central neurotransmitter systems. Carbaryl and aldicarb were injected in ovo on day 15 of incubation at 6, 16 and 65 mg kg-1 egg weight and at 0.2, 0.4 and 35 mg kg-1 egg weight, respectively. Neurotransmitter levels (assayed by high performance liquid chromatography with electrochemical detection) and locomotion were measured at various times (1-43 days) after dosing. At the lower doses of both carbaryl and aldicarb, a trend towards prolonged decreases in cerebral dopamine and homovanillic acid was seen. The high dose of carbaryl significantly reduced dopamine and the high dose of both compounds significantly decreased homovanillic acid and 5-hydroxyindoleacetic acid. Persistent locomotion alterations were observed only at the higher doses of both carbaryl and aldicarb when the specific neurotransmitters measured returned to normal levels.", "contents": "Chick embryo exposure to carbamates alters neurochemical parameters and behavior. Recent evidence has shown that exposure to pesticides can lead to long-term neurophysiological and functional deficits. We have demonstrated previously that locomotion in chicks exposed to some organophosphates and carbamates could be altered persistently without concomitant central or peripheral esterase inhibition. Furthermore, histopathology of the ataxic chickens showed no lesions in either the central or peripheral systems. In this study, we examined whether locomotion alterations seen in chicks exposed in ovo to carbaryl and aldicarb are accompanied by perturbations in particular central neurotransmitter systems. Carbaryl and aldicarb were injected in ovo on day 15 of incubation at 6, 16 and 65 mg kg-1 egg weight and at 0.2, 0.4 and 35 mg kg-1 egg weight, respectively. Neurotransmitter levels (assayed by high performance liquid chromatography with electrochemical detection) and locomotion were measured at various times (1-43 days) after dosing. At the lower doses of both carbaryl and aldicarb, a trend towards prolonged decreases in cerebral dopamine and homovanillic acid was seen. The high dose of carbaryl significantly reduced dopamine and the high dose of both compounds significantly decreased homovanillic acid and 5-hydroxyindoleacetic acid. Persistent locomotion alterations were observed only at the higher doses of both carbaryl and aldicarb when the specific neurotransmitters measured returned to normal levels."} {"id": "PMID:1280659", "title": "[New approaches to the diagnosis of carbohydrate metabolic disorders].", "content": "A bioenergetic conception of insulin-independent diabetes mellitus (IIDM) is put forward. Molecular mechanisms of carbohydrate and fat metabolism are discussed which result in a vicious regulatory cycle to provoke a transition to stable pathology. Previously unknown role of human saliva in oral cavity in this regulatory cycle is revealed. New diagnostic tests are developed on the basis of the conception on IIDM pathogenesis. The results of clinical trials are presented which have been obtained during population screening.", "contents": "[New approaches to the diagnosis of carbohydrate metabolic disorders]. A bioenergetic conception of insulin-independent diabetes mellitus (IIDM) is put forward. Molecular mechanisms of carbohydrate and fat metabolism are discussed which result in a vicious regulatory cycle to provoke a transition to stable pathology. Previously unknown role of human saliva in oral cavity in this regulatory cycle is revealed. New diagnostic tests are developed on the basis of the conception on IIDM pathogenesis. The results of clinical trials are presented which have been obtained during population screening."} {"id": "PMID:1280662", "title": "Is your audiovisual teaching effective?", "content": "Medical illustrators produce vast numbers of images used in audiovisual programmes for medical teaching. We know that students can learn by using audiovisual teaching materials but do not always know how well they learn, particularly in comparison with other teaching methods. To find out how effective audiovisual teaching is, it must be evaluated or measured. This paper looks at the evaluation of a range of medical audiovisual teaching programmes and their effectiveness by observation, questionnaire, tests and examinations.", "contents": "Is your audiovisual teaching effective? Medical illustrators produce vast numbers of images used in audiovisual programmes for medical teaching. We know that students can learn by using audiovisual teaching materials but do not always know how well they learn, particularly in comparison with other teaching methods. To find out how effective audiovisual teaching is, it must be evaluated or measured. This paper looks at the evaluation of a range of medical audiovisual teaching programmes and their effectiveness by observation, questionnaire, tests and examinations."} {"id": "PMID:1280663", "title": "Immunodiagnosis of human dirofilariasis by enzyme-linked immunosorbent assay using recombinant DNA-derived fusion protein.", "content": "An enzyme-linked immunosorbent assay (ELISA) using antigenic beta-galactosidase-Dirofilaria immitis recombinant fusion protein (FP) obtained by the recombinant DNA technique provided a useful diagnostic tool for human dirofilariasis. D. immitis-infected human sera reacted strongly with FP that was immobilized with anti-beta-galactosidase monoclonal antibody on microplates. However, the FP did not react with sera from patients with other filariasis. In detection of anti-D. immitis IgG antibody. ELISA using FP was highly sensitive and specific compared to that using crude somatic antigen.", "contents": "Immunodiagnosis of human dirofilariasis by enzyme-linked immunosorbent assay using recombinant DNA-derived fusion protein. An enzyme-linked immunosorbent assay (ELISA) using antigenic beta-galactosidase-Dirofilaria immitis recombinant fusion protein (FP) obtained by the recombinant DNA technique provided a useful diagnostic tool for human dirofilariasis. D. immitis-infected human sera reacted strongly with FP that was immobilized with anti-beta-galactosidase monoclonal antibody on microplates. However, the FP did not react with sera from patients with other filariasis. In detection of anti-D. immitis IgG antibody. ELISA using FP was highly sensitive and specific compared to that using crude somatic antigen."} {"id": "PMID:1280664", "title": "Use of an aceto-carmine procedure to examine the excysted metacercariae of Echinostoma caproni and E. trivolvis.", "content": "A simple aceto-carmine procedure was developed to relax, fix, stain, and clear excysted metacercariae of Echinostoma caproni and E. trivolvis. This procedure allowed for morphologic details on whole metacercariae comparable to those seen with more elaborate staining procedures. Differences in dimensions and staining intensities between the two species of metacercariae are described.", "contents": "Use of an aceto-carmine procedure to examine the excysted metacercariae of Echinostoma caproni and E. trivolvis. A simple aceto-carmine procedure was developed to relax, fix, stain, and clear excysted metacercariae of Echinostoma caproni and E. trivolvis. This procedure allowed for morphologic details on whole metacercariae comparable to those seen with more elaborate staining procedures. Differences in dimensions and staining intensities between the two species of metacercariae are described."} {"id": "PMID:1280665", "title": "Preservation of RNA for in situ hybridization: Carnoy's versus formaldehyde fixation.", "content": "Tissues fixed with organic solvent fixatives such as Carnoy's solution are known to give poor and erratic results with in situ hybridization, whereas those fixed with paraformaldehyde produce more consistent results. To understand this difference and to improve the utility of Carnoy's-fixed tissue for in situ hybridization, we explored several parameters of RNA integrity and preservation. Carnoy's-fixed, paraffin-embedded livers and paraformaldehyde-fixed, paraffin-embedded livers of mice were compared for RNA extractability, degradation, and hybridizability. In addition, retention of RNA in tissue sections after sequential in situ hybridization treatments was compared. RNA was found to be easily extractable from Carnoy's-fixed liver and was well preserved, with only slight degradation of high molecular weight RNA. Conversely, only a small percentage of the RNA was extractable from paraformaldehyde-fixed liver unless the tissue was digested with protease. The extracted RNA was well preserved, without detectable degradation. Sections of tissue fixed in Carnoy's solution subjected to in situ hybridization retained only about 10% of their original RNA content and gave correspondingly weak in situ hybridization signals. Formaldehyde-fixed tissues retained much more of the RNA (about 45%) and produced strong in situ hybridization signals. Treatment of Carnoy's-fixed tissue sections with vaporous formaldehyde increased retention of RNA and provided in situ hybridization signals comparable with those of paraformaldehyde-fixed tissues.", "contents": "Preservation of RNA for in situ hybridization: Carnoy's versus formaldehyde fixation. Tissues fixed with organic solvent fixatives such as Carnoy's solution are known to give poor and erratic results with in situ hybridization, whereas those fixed with paraformaldehyde produce more consistent results. To understand this difference and to improve the utility of Carnoy's-fixed tissue for in situ hybridization, we explored several parameters of RNA integrity and preservation. Carnoy's-fixed, paraffin-embedded livers and paraformaldehyde-fixed, paraffin-embedded livers of mice were compared for RNA extractability, degradation, and hybridizability. In addition, retention of RNA in tissue sections after sequential in situ hybridization treatments was compared. RNA was found to be easily extractable from Carnoy's-fixed liver and was well preserved, with only slight degradation of high molecular weight RNA. Conversely, only a small percentage of the RNA was extractable from paraformaldehyde-fixed liver unless the tissue was digested with protease. The extracted RNA was well preserved, without detectable degradation. Sections of tissue fixed in Carnoy's solution subjected to in situ hybridization retained only about 10% of their original RNA content and gave correspondingly weak in situ hybridization signals. Formaldehyde-fixed tissues retained much more of the RNA (about 45%) and produced strong in situ hybridization signals. Treatment of Carnoy's-fixed tissue sections with vaporous formaldehyde increased retention of RNA and provided in situ hybridization signals comparable with those of paraformaldehyde-fixed tissues."} {"id": "PMID:1280666", "title": "Loss of laminin epitopes during glomerular basement membrane assembly in developing mouse kidneys.", "content": "Kidney glomerular basement membranes (GMBs) originate in development from fusion of a dual basement membrane between endothelial cells and primitive epithelial podocytes. After fusion, segments of newly synthesized matrix, derived primarily from podocytes, appear as subepithelial outpockets and are spliced into GBMs during glomerular capillary loop expansion. To investigate GBM assembly further, we examined newborn mouse kidneys with monoclonal rat anti-mouse laminin IgGs (MAb) conjugated to horseradish peroxidase (HRP). In adults, these MAb strongly label glomerular mesangial matrices but bind only weakly or not at all to mature GBMs. In contrast, anti-laminin MAb intensely bound newborn mouse GBMs undergoing initial assembly. After intraperitoneal injection of MAb-HRP into neonates, dense binding occurred across both subendothelial and subepithelial pre-fusion GMBs as well as forming mesangial matrices. Considerably less MAb binding was seen, however, in post-fusion GBMs from more mature glomeruli in the same section, although mesangial matrices remained positive. In addition, new subepithelial segments in areas of splicing were negative. These results conflict with those obtained previously with injections of polyclonal anti-laminin IgGs into newborns or adults, which result in complete labeling of all GBMs. Although epitope masking cannot be completely excluded, we believe that decreased MAb binding to developing GBM reflects actual epitope loss. This loss could occur by laminin isoform substitution, conformational change, and/or proteolytic processing during GBM assembly.", "contents": "Loss of laminin epitopes during glomerular basement membrane assembly in developing mouse kidneys. Kidney glomerular basement membranes (GMBs) originate in development from fusion of a dual basement membrane between endothelial cells and primitive epithelial podocytes. After fusion, segments of newly synthesized matrix, derived primarily from podocytes, appear as subepithelial outpockets and are spliced into GBMs during glomerular capillary loop expansion. To investigate GBM assembly further, we examined newborn mouse kidneys with monoclonal rat anti-mouse laminin IgGs (MAb) conjugated to horseradish peroxidase (HRP). In adults, these MAb strongly label glomerular mesangial matrices but bind only weakly or not at all to mature GBMs. In contrast, anti-laminin MAb intensely bound newborn mouse GBMs undergoing initial assembly. After intraperitoneal injection of MAb-HRP into neonates, dense binding occurred across both subendothelial and subepithelial pre-fusion GMBs as well as forming mesangial matrices. Considerably less MAb binding was seen, however, in post-fusion GBMs from more mature glomeruli in the same section, although mesangial matrices remained positive. In addition, new subepithelial segments in areas of splicing were negative. These results conflict with those obtained previously with injections of polyclonal anti-laminin IgGs into newborns or adults, which result in complete labeling of all GBMs. Although epitope masking cannot be completely excluded, we believe that decreased MAb binding to developing GBM reflects actual epitope loss. This loss could occur by laminin isoform substitution, conformational change, and/or proteolytic processing during GBM assembly."} {"id": "PMID:1280667", "title": "Simultaneous visualization of immunodetected antigens and tissue components revealed by non-enzymatic histochemical stains.", "content": "We explored the possibility of simultaneous application of histochemical and immunohistochemical staining techniques on the same paraffin-embedded human tissue section. Conventional histological stains (PAS, Alcian, Alcian-PAS, Van Gieson, Gomori silver impregnation, and Giemsa) were used in association with a battery of markers (keratins, leucocyte common antigen, S-100 protein, Factor VIII-related antigen) that are widely employed in diagnostic and experimental studies. We found that the best procedure was to perform immunostaining before the histochemical reaction, as this enables all the other possible combinations to be carried out. In addition, several detection systems, such as peroxidase-anti-peroxidase (PAP), alkaline phosphatase-anti-alkaline phosphatase (APAAP), and avidin-biotin complex (ABC), were tested and all gave consistent results. Some minor modifications of the histological staining methods were necessary, but the current immunohistochemical techniques could be used as established. Preliminary findings indicate that immunohistochemistry can be combined with histochemistry techniques by means of a relatively simple procedure whose only disadvantage is the time required to carry out the double staining.", "contents": "Simultaneous visualization of immunodetected antigens and tissue components revealed by non-enzymatic histochemical stains. We explored the possibility of simultaneous application of histochemical and immunohistochemical staining techniques on the same paraffin-embedded human tissue section. Conventional histological stains (PAS, Alcian, Alcian-PAS, Van Gieson, Gomori silver impregnation, and Giemsa) were used in association with a battery of markers (keratins, leucocyte common antigen, S-100 protein, Factor VIII-related antigen) that are widely employed in diagnostic and experimental studies. We found that the best procedure was to perform immunostaining before the histochemical reaction, as this enables all the other possible combinations to be carried out. In addition, several detection systems, such as peroxidase-anti-peroxidase (PAP), alkaline phosphatase-anti-alkaline phosphatase (APAAP), and avidin-biotin complex (ABC), were tested and all gave consistent results. Some minor modifications of the histological staining methods were necessary, but the current immunohistochemical techniques could be used as established. Preliminary findings indicate that immunohistochemistry can be combined with histochemistry techniques by means of a relatively simple procedure whose only disadvantage is the time required to carry out the double staining."} {"id": "PMID:1280672", "title": "Amylase-producing IgD-type multiple myeloma.", "content": "We describe the case of a 63-year-old woman with an IgD-type multiple myeloma and hyperamylasaemia. The evolution of the amylase concentration, the immunohistochemical data and the intracellular amylase contents of the plasma cell were consistent with secretion of amylase by the malignant clone. Moreover, cytogenetic analysis of the bone marrow revealed two structural rearrangements involving chromosome 1 near the amylase locus. Multiple myeloma should be added to the amylase-secreting tumours. This rare entity is not confined to Japan, where it was first recognized.", "contents": "Amylase-producing IgD-type multiple myeloma. We describe the case of a 63-year-old woman with an IgD-type multiple myeloma and hyperamylasaemia. The evolution of the amylase concentration, the immunohistochemical data and the intracellular amylase contents of the plasma cell were consistent with secretion of amylase by the malignant clone. Moreover, cytogenetic analysis of the bone marrow revealed two structural rearrangements involving chromosome 1 near the amylase locus. Multiple myeloma should be added to the amylase-secreting tumours. This rare entity is not confined to Japan, where it was first recognized."} {"id": "PMID:1280673", "title": "A promising interferon plus four-drug chemotherapy regimen for metastatic melanoma.", "content": "The goal of this study was to determine the therapeutic efficacy and toxicity of a four-drug chemotherapy regimen combined with natural leukocyte interferon alfa (IFN-alpha) for metastatic melanoma. Between December 1988 and December 1991, 48 consecutive unselected patients with metastatic melanoma were entered onto this phase II study. Forty-five of these patients were assessable for response and 46 for toxicity. The four-drug chemotherapy regimen was as follows: dacarbazine (DTIC) 200 mg/m2 days 1 to 5, vincristine 1 mg/m2 days 1 and 4, bleomycin 15 mg days 2 and 5 intravenously (IV), and lomustine (CCNU) 80 mg day 1 orally. IFN-alpha, initiated day 8, was administered 3 x 10(6) IU/d, subcutaneously (SC) for 6 weeks, followed by 6 x 10(6) IU three times per week. A small protocol modification was adopted from the 21st patient onwards whenever there was more than 2 months' stabilization or progression with the original protocol: IFN therapy was split into 2-week treatment periods interrupted by a 2-week rest period. Among the 45 assessable patients, the objective response rate was 62% (95% confidence limit, 48 to 77); six patients (13%) achieved a complete response (CR) and 22 (49%) a partial response (PR). Metastases in such sites as liver also responded favorably (one CR, six PR, one stable disease [SD], two progressive disease [PD]). After splitting IFN therapy for nonresponders, in two patients PD and in another two patients SD changed into regression. Three of the six patients with a CR have suffered a relapse, but the other three have been off treatment for 7, 18, and 31 months without recurrence. Most of the symptomatic patients also experienced rapid relief of symptoms. Overall toxicity of this mainly outpatient regimen seemed to be acceptable. One patient died of a septic fever with grade 4 leukopenia and thrombocytopenia. The most frequent side effects were transient fever, nausea/vomiting, fatigue, and grade I/II hematologic toxicity. Results demonstrate a remarkably high response rate in combining IFN-alpha and four chemotherapeutic agents. The apparent schedule-dependency of responses must be further explored in a controlled phase III study.", "contents": "A promising interferon plus four-drug chemotherapy regimen for metastatic melanoma. The goal of this study was to determine the therapeutic efficacy and toxicity of a four-drug chemotherapy regimen combined with natural leukocyte interferon alfa (IFN-alpha) for metastatic melanoma. Between December 1988 and December 1991, 48 consecutive unselected patients with metastatic melanoma were entered onto this phase II study. Forty-five of these patients were assessable for response and 46 for toxicity. The four-drug chemotherapy regimen was as follows: dacarbazine (DTIC) 200 mg/m2 days 1 to 5, vincristine 1 mg/m2 days 1 and 4, bleomycin 15 mg days 2 and 5 intravenously (IV), and lomustine (CCNU) 80 mg day 1 orally. IFN-alpha, initiated day 8, was administered 3 x 10(6) IU/d, subcutaneously (SC) for 6 weeks, followed by 6 x 10(6) IU three times per week. A small protocol modification was adopted from the 21st patient onwards whenever there was more than 2 months' stabilization or progression with the original protocol: IFN therapy was split into 2-week treatment periods interrupted by a 2-week rest period. Among the 45 assessable patients, the objective response rate was 62% (95% confidence limit, 48 to 77); six patients (13%) achieved a complete response (CR) and 22 (49%) a partial response (PR). Metastases in such sites as liver also responded favorably (one CR, six PR, one stable disease [SD], two progressive disease [PD]). After splitting IFN therapy for nonresponders, in two patients PD and in another two patients SD changed into regression. Three of the six patients with a CR have suffered a relapse, but the other three have been off treatment for 7, 18, and 31 months without recurrence. Most of the symptomatic patients also experienced rapid relief of symptoms. Overall toxicity of this mainly outpatient regimen seemed to be acceptable. One patient died of a septic fever with grade 4 leukopenia and thrombocytopenia. The most frequent side effects were transient fever, nausea/vomiting, fatigue, and grade I/II hematologic toxicity. Results demonstrate a remarkably high response rate in combining IFN-alpha and four chemotherapeutic agents. The apparent schedule-dependency of responses must be further explored in a controlled phase III study."} {"id": "PMID:1280674", "title": "Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor infusion makes high-dose etoposide a safe outpatient regimen that is effective in lymphoma and myeloma patients.", "content": "This study assessed the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or recombinant human granulocyte colony-stimulating factor (rhG-CSF) in ameliorating the extent and duration of hematologic toxicity after high-dose etoposide cancer therapy. Thirty-two non-Hodgkin's lymphoma and myeloma patients were treated with 2 to 2.4 g/m2 etoposide infused intravenously (IV) during a 10- to 12-hour period, followed 72 hours later by subcutaneous administration of rhGM-CSF or rhG-CSF. Hematologic toxicity was compared with that observed in 29 patients who were treated with high-dose etoposide without growth factors. The median duration of grade 4 neutropenia in growth factor-treated patients was 3 days, and granulocyte counts never decreased to less than 100/microL in approximately half of the patients. The corresponding figures in the control patients were 8 and 3 days, respectively (P < .0001). No effect was observed in platelet and RBC recovery. Growth factor-treated patients became eligible to receive additional myelotoxic chemotherapy a median of 5 days earlier than controls. Nonhematologic toxicity was minimal. Grade 1 mucositis was observed in two of 61 patients (3%). Antitumor activity assessed within 1 month after etoposide administration was documented in 58% of 38 assessable patients. Finally, high-dose etoposide expanded and mobilized the pool of peripheral-blood hematopoietic progenitors. The use of rhGM-CSF or rhG-CSF makes high-dose etoposide a safe outpatient regimen and should encourage the inclusion of this highly effective and well-tolerated drug in novel treatment strategies that use high-dose therapy early in the clinical course of chemosensitive tumors.", "contents": "Granulocyte-macrophage colony-stimulating factor or granulocyte colony-stimulating factor infusion makes high-dose etoposide a safe outpatient regimen that is effective in lymphoma and myeloma patients. This study assessed the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or recombinant human granulocyte colony-stimulating factor (rhG-CSF) in ameliorating the extent and duration of hematologic toxicity after high-dose etoposide cancer therapy. Thirty-two non-Hodgkin's lymphoma and myeloma patients were treated with 2 to 2.4 g/m2 etoposide infused intravenously (IV) during a 10- to 12-hour period, followed 72 hours later by subcutaneous administration of rhGM-CSF or rhG-CSF. Hematologic toxicity was compared with that observed in 29 patients who were treated with high-dose etoposide without growth factors. The median duration of grade 4 neutropenia in growth factor-treated patients was 3 days, and granulocyte counts never decreased to less than 100/microL in approximately half of the patients. The corresponding figures in the control patients were 8 and 3 days, respectively (P < .0001). No effect was observed in platelet and RBC recovery. Growth factor-treated patients became eligible to receive additional myelotoxic chemotherapy a median of 5 days earlier than controls. Nonhematologic toxicity was minimal. Grade 1 mucositis was observed in two of 61 patients (3%). Antitumor activity assessed within 1 month after etoposide administration was documented in 58% of 38 assessable patients. Finally, high-dose etoposide expanded and mobilized the pool of peripheral-blood hematopoietic progenitors. The use of rhGM-CSF or rhG-CSF makes high-dose etoposide a safe outpatient regimen and should encourage the inclusion of this highly effective and well-tolerated drug in novel treatment strategies that use high-dose therapy early in the clinical course of chemosensitive tumors."} {"id": "PMID:1280676", "title": "Leucine excess under conditions of low or compensated aminoacidemia does not change skeletal muscle and whole-body protein synthesis in suckling lambs during postprandial period.", "content": "We determined the effect of a 4-h leucine infusion, leading to 15-fold elevated plasma leucine concentrations, on skeletal muscle and whole-body protein synthesis in suckling lambs during the postprandial period. The [3H]phenylalanine large dose method was validated and used to quantify the fractional rates of protein synthesis (Ks in %/d) at the end of the leucine infusion. In the first experiment leucine infusion lowered plasma amino acid concentrations but did not change the Ks, the capacity for protein synthesis (Cs, mg RNA/g protein) or the efficiency of translation [g protein synthesized/(d-g RNA)] in any muscles studied or the whole body. In the second experiment the leucine-induced decreases in plasma amino acid concentrations were compensated by the simultaneous infusion of substantial amounts of amino acids. Again leucine excess did not significantly change Ks, Cs and efficiency of protein synthesis. These results indicated that leucine excess in suckling lambs during the postprandial period lowered aminoacidemia without any change of the protein synthesis rates in skeletal muscles or the whole body.", "contents": "Leucine excess under conditions of low or compensated aminoacidemia does not change skeletal muscle and whole-body protein synthesis in suckling lambs during postprandial period. We determined the effect of a 4-h leucine infusion, leading to 15-fold elevated plasma leucine concentrations, on skeletal muscle and whole-body protein synthesis in suckling lambs during the postprandial period. The [3H]phenylalanine large dose method was validated and used to quantify the fractional rates of protein synthesis (Ks in %/d) at the end of the leucine infusion. In the first experiment leucine infusion lowered plasma amino acid concentrations but did not change the Ks, the capacity for protein synthesis (Cs, mg RNA/g protein) or the efficiency of translation [g protein synthesized/(d-g RNA)] in any muscles studied or the whole body. In the second experiment the leucine-induced decreases in plasma amino acid concentrations were compensated by the simultaneous infusion of substantial amounts of amino acids. Again leucine excess did not significantly change Ks, Cs and efficiency of protein synthesis. These results indicated that leucine excess in suckling lambs during the postprandial period lowered aminoacidemia without any change of the protein synthesis rates in skeletal muscles or the whole body."} {"id": "PMID:1280677", "title": "Angiogenic activity of fibrin degradation products is located in fibrin fragment E.", "content": "The source of angiogenic activity of fibrin degradation products has been sought in a series of experiments, applying degradation products from different types of fibrin and fibrinogen to the chick chorioallantoic membrane. The presence of platelets or fibronectin during clotting was not essential for activity, and neither was crosslinking. Fibrinogen degradation products were non-stimulatory, as was serum. Molecular sieve column chromatography indicated a range of active fragments. Admixture of active fibrin degradation products with antifibrin fragment E, but not D, antiserum neutralized activity. Preparations containing only fibrin fragment E retained activity. A commercial preparation of fibrinogen fragment E was inactive until treated with thrombin. These experiments point to fibrin fragment E being the source of angiogenic activity, with thrombin cleavage being the essential step in generating activity.", "contents": "Angiogenic activity of fibrin degradation products is located in fibrin fragment E. The source of angiogenic activity of fibrin degradation products has been sought in a series of experiments, applying degradation products from different types of fibrin and fibrinogen to the chick chorioallantoic membrane. The presence of platelets or fibronectin during clotting was not essential for activity, and neither was crosslinking. Fibrinogen degradation products were non-stimulatory, as was serum. Molecular sieve column chromatography indicated a range of active fragments. Admixture of active fibrin degradation products with antifibrin fragment E, but not D, antiserum neutralized activity. Preparations containing only fibrin fragment E retained activity. A commercial preparation of fibrinogen fragment E was inactive until treated with thrombin. These experiments point to fibrin fragment E being the source of angiogenic activity, with thrombin cleavage being the essential step in generating activity."} {"id": "PMID:1280678", "title": "The \"plaque-free zone\" in health and disease: a scanning electron microscope study.", "content": "A \"plaque-free\" zone has been described on the enamel surface of healthy extracted teeth. This study examined this zone on chronic adult periodontitis-affected teeth (CAPT). Ten healthy controls and 16 CAPT were collected immediately after extraction, fixed, dehydrated, critical point dried, coated, and viewed by scanning electron microscopy (SEM). The \"plaque-free\" zone was observed in both groups as an area with few bacteria between the apical plaque border and the coronal limit of an epithelial layer on the root surface, extending to the residual periodontal ligament. On the healthy specimens, the apical plaque border consisted mainly of cocci and short rods, while on the CAPT specimens spirochetes predominated. Isolated or small groups of microorganisms were always present in the \"plaque-free\" zone and at its apical limit, close to or in contact with junctional epithelial cells. This zone is therefore not completely free of plaque, as suggested. It was concluded that a tissue complex, analogous to that in health on enamel, persists on the root surfaces of CAPT throughout the disease process. It comprises a discrete plaque border, a dental cuticle with sparse organisms, and an epithelium analogous to junctional epithelium. Its main function would appear to be to prevent bulk access of plaque to the surrounding tissues, including direct contact of bacteria with underlying ligament.", "contents": "The \"plaque-free zone\" in health and disease: a scanning electron microscope study. A \"plaque-free\" zone has been described on the enamel surface of healthy extracted teeth. This study examined this zone on chronic adult periodontitis-affected teeth (CAPT). Ten healthy controls and 16 CAPT were collected immediately after extraction, fixed, dehydrated, critical point dried, coated, and viewed by scanning electron microscopy (SEM). The \"plaque-free\" zone was observed in both groups as an area with few bacteria between the apical plaque border and the coronal limit of an epithelial layer on the root surface, extending to the residual periodontal ligament. On the healthy specimens, the apical plaque border consisted mainly of cocci and short rods, while on the CAPT specimens spirochetes predominated. Isolated or small groups of microorganisms were always present in the \"plaque-free\" zone and at its apical limit, close to or in contact with junctional epithelial cells. This zone is therefore not completely free of plaque, as suggested. It was concluded that a tissue complex, analogous to that in health on enamel, persists on the root surfaces of CAPT throughout the disease process. It comprises a discrete plaque border, a dental cuticle with sparse organisms, and an epithelium analogous to junctional epithelium. Its main function would appear to be to prevent bulk access of plaque to the surrounding tissues, including direct contact of bacteria with underlying ligament."} {"id": "PMID:1280679", "title": "Retardation of epithelial migration in monkeys using a carbon dioxide laser: an animal study.", "content": "Obtaining a connective tissue attachment to the root surface following a mucoperiosteal flap surgery has been a goal of periodontal therapy for a long time. The objective of this study was to examine whether controlled de-epithelialization with the CO2 laser would retard the apical migration of the epithelium and thereby increase the amount of connective tissue attachment. Elastics were placed on the maxillary premolars and incisors of 7 cynomolgus monkeys to create periodontal defects. Open flap debridement was performed on each side. On the experimental side, the oral epithelium was removed by CO2 laser irradiation. This report describes the 3 specimens at 7, 14, and 28 days respectively. On the control side sulcular epithelium was seen at 14 days. Sulcular epithelium was first seen on the test side at 28 days. For all specimens over 7 days, there was a trend to less epithelium and more connective tissue attachment on the experimental side than on the control side. However, no statistical analysis was possible on this histologic study. The CO2 laser may be a useful tool to retard epithelium and thereby enhance new connective tissue attachment.", "contents": "Retardation of epithelial migration in monkeys using a carbon dioxide laser: an animal study. Obtaining a connective tissue attachment to the root surface following a mucoperiosteal flap surgery has been a goal of periodontal therapy for a long time. The objective of this study was to examine whether controlled de-epithelialization with the CO2 laser would retard the apical migration of the epithelium and thereby increase the amount of connective tissue attachment. Elastics were placed on the maxillary premolars and incisors of 7 cynomolgus monkeys to create periodontal defects. Open flap debridement was performed on each side. On the experimental side, the oral epithelium was removed by CO2 laser irradiation. This report describes the 3 specimens at 7, 14, and 28 days respectively. On the control side sulcular epithelium was seen at 14 days. Sulcular epithelium was first seen on the test side at 28 days. For all specimens over 7 days, there was a trend to less epithelium and more connective tissue attachment on the experimental side than on the control side. However, no statistical analysis was possible on this histologic study. The CO2 laser may be a useful tool to retard epithelium and thereby enhance new connective tissue attachment."} {"id": "PMID:1280680", "title": "Effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide in volunteers.", "content": "The effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide (VIP) was studied in 7 healthy subjects and 8 subjects with the common cold. Before terfenadine administration, the mean plasma substance P concentration of the subjects with the common cold was significantly higher than that of the healthy subjects. The increased mean plasma substance P concentration of the subjects with the common cold was decreased after terfenadine administration. In the healthy subjects, the mean plasma substance P concentration was unchanged by terfenadine administration. The mean plasma VIP concentration of the subjects with common cold was slightly higher than that of the healthy subjects before and after terfenadine administration, with no significant difference.", "contents": "Effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide in volunteers. The effect of terfenadine on the plasma concentrations of substance P and vasoactive intestinal polypeptide (VIP) was studied in 7 healthy subjects and 8 subjects with the common cold. Before terfenadine administration, the mean plasma substance P concentration of the subjects with the common cold was significantly higher than that of the healthy subjects. The increased mean plasma substance P concentration of the subjects with the common cold was decreased after terfenadine administration. In the healthy subjects, the mean plasma substance P concentration was unchanged by terfenadine administration. The mean plasma VIP concentration of the subjects with common cold was slightly higher than that of the healthy subjects before and after terfenadine administration, with no significant difference."} {"id": "PMID:1280681", "title": "Effects of long-term laxative treatment on neuropeptides in rat mesenteric vessels and caecum.", "content": "In order to investigate the toxic effects of long-term treatment with anthraquinone laxatives, rats were fed either chocolate alone, or chocolate adulterated with senna or danthron (1,8-dihydroxyanthraquinone) for 5 months. Mesenteric blood vessels and the outer muscle layers of the caecum, together with the myenteric plexus, were examined using ultrastructural, histochemical, immunohistochemical and immunoassay techniques. There was no ultrastructural evidence of degeneration in either the mesenteric vessels or the caecum. In the mesenteric vessels, levels of neuropeptide Y were significantly reduced in the danthron-fed rats, but levels of substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were unaffected by all treatments. In the caecum, VIP-, SP- and CGRP-immunoreactivity and catecholamine-fluorescence were unchanged by the laxative treatments.", "contents": "Effects of long-term laxative treatment on neuropeptides in rat mesenteric vessels and caecum. In order to investigate the toxic effects of long-term treatment with anthraquinone laxatives, rats were fed either chocolate alone, or chocolate adulterated with senna or danthron (1,8-dihydroxyanthraquinone) for 5 months. Mesenteric blood vessels and the outer muscle layers of the caecum, together with the myenteric plexus, were examined using ultrastructural, histochemical, immunohistochemical and immunoassay techniques. There was no ultrastructural evidence of degeneration in either the mesenteric vessels or the caecum. In the mesenteric vessels, levels of neuropeptide Y were significantly reduced in the danthron-fed rats, but levels of substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were unaffected by all treatments. In the caecum, VIP-, SP- and CGRP-immunoreactivity and catecholamine-fluorescence were unchanged by the laxative treatments."} {"id": "PMID:1280682", "title": "Comparative immunogenicity of gp120-derived proteins and their induction of anti-V3 loop region antibodies.", "content": "This report compares the immunogenicity of three different preparations of gp120 [the envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) virus]: (a) native, fully glycosylated gp120; (b) a nonglycosylated, denatured form of gp120; and (c) a nonglycosylated peptide representing the \"immunodominant\" third hypervariable region of the gp120 molecule. Results indicate that the native glycosylated form of gp120 induces a maximal anti-HIV response in which a majority of B cells bind to conformation-dependent epitopes but less than one-fifth recognize the V3 loop region.", "contents": "Comparative immunogenicity of gp120-derived proteins and their induction of anti-V3 loop region antibodies. This report compares the immunogenicity of three different preparations of gp120 [the envelope glycoprotein of the human immunodeficiency virus type 1 (HIV-1) virus]: (a) native, fully glycosylated gp120; (b) a nonglycosylated, denatured form of gp120; and (c) a nonglycosylated peptide representing the \"immunodominant\" third hypervariable region of the gp120 molecule. Results indicate that the native glycosylated form of gp120 induces a maximal anti-HIV response in which a majority of B cells bind to conformation-dependent epitopes but less than one-fifth recognize the V3 loop region."} {"id": "PMID:1280683", "title": "Replication and apical budding of HIV-1 in mucous-secreting colonic epithelial cells.", "content": "The human colonic adenocarcinoma cell line HT29 can be infected with various isolates of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). In some cases, the virus was able to perform its complete cycle of replication as demonstrated by the persistent production of mature viral particles in the cell-free culture supernatant. We have cultured HT29 cells chronically infected with the replicative strain HIV1-NDK in a chemically defined serum-free medium. Under these conditions, the cells were able to maintain a high level of viral replication, as demonstrated by reverse transcriptase activities and in situ hybridization studies. By indirect immunofluorescence labeling and electron microscopy, we observed that serum starvation was associated with the differentiation of HIV-1-infected HT29 cells into mucous-secreting cells resembling epithelial goblet cells of the colonic mucosa. These mucous-secreting cells, which accounted for 50% of the overall population, produced mature particles of HIV through their apical membrane in the vicinity of mucous granules. These data suggest that HIV-infected goblet cells in the colonic mucosa may produce the virus in the colorectal lumen; this could explain the route of transmission of HIV in the case of anal intercourse.", "contents": "Replication and apical budding of HIV-1 in mucous-secreting colonic epithelial cells. The human colonic adenocarcinoma cell line HT29 can be infected with various isolates of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2). In some cases, the virus was able to perform its complete cycle of replication as demonstrated by the persistent production of mature viral particles in the cell-free culture supernatant. We have cultured HT29 cells chronically infected with the replicative strain HIV1-NDK in a chemically defined serum-free medium. Under these conditions, the cells were able to maintain a high level of viral replication, as demonstrated by reverse transcriptase activities and in situ hybridization studies. By indirect immunofluorescence labeling and electron microscopy, we observed that serum starvation was associated with the differentiation of HIV-1-infected HT29 cells into mucous-secreting cells resembling epithelial goblet cells of the colonic mucosa. These mucous-secreting cells, which accounted for 50% of the overall population, produced mature particles of HIV through their apical membrane in the vicinity of mucous granules. These data suggest that HIV-infected goblet cells in the colonic mucosa may produce the virus in the colorectal lumen; this could explain the route of transmission of HIV in the case of anal intercourse."} {"id": "PMID:1280685", "title": "Sperm immobilizing antibodies react to the 3-O-sulfated galactose residue of seminolipid on human sperm.", "content": "It is well known that very few women who possess sperm immobilizing antibodies in their sera can conceive naturally even though there are no abnormalities in their reproductive organs on routine medical examination. A monoclonal antibody (MAb), designated 2H12, was produced by immunizing a BALB/c mouse with the human choriocarcinoma cell line JEG-3. MAb 2H12 showed strong sperm immobilizing activities and reacted to sulfatide and seminolipids. The sperm immobilizing activities of 2H12 were clearly absorbed with sulfatide or seminolipid whilst several other sperm immobilizing MAbs that were made by immunization with human sperm or seminal plasma could not be absorbed with the same sulfoglycolipids. The sperm immobilizing antibodies in the sera of infertile women with unknown cause were also clearly absorbed with sulfatide or seminolipid. MAb 2H12-conjugated immunobeads (MAb 2H12-IMBs) bound to motile sperm. This binding of 2H12-IMBs to sperm was competitively inhibited either by 2H12 or women's sera containing sperm immobilizing antibodies, but not by normal women's sera or several other sperm immobilizing MAbs to human sperm. These results suggest that the sperm immobilizing antibody in women's sera is directed against the 3-O-sulfogalactose residue of seminolipid on the sperm membrane.", "contents": "Sperm immobilizing antibodies react to the 3-O-sulfated galactose residue of seminolipid on human sperm. It is well known that very few women who possess sperm immobilizing antibodies in their sera can conceive naturally even though there are no abnormalities in their reproductive organs on routine medical examination. A monoclonal antibody (MAb), designated 2H12, was produced by immunizing a BALB/c mouse with the human choriocarcinoma cell line JEG-3. MAb 2H12 showed strong sperm immobilizing activities and reacted to sulfatide and seminolipids. The sperm immobilizing activities of 2H12 were clearly absorbed with sulfatide or seminolipid whilst several other sperm immobilizing MAbs that were made by immunization with human sperm or seminal plasma could not be absorbed with the same sulfoglycolipids. The sperm immobilizing antibodies in the sera of infertile women with unknown cause were also clearly absorbed with sulfatide or seminolipid. MAb 2H12-conjugated immunobeads (MAb 2H12-IMBs) bound to motile sperm. This binding of 2H12-IMBs to sperm was competitively inhibited either by 2H12 or women's sera containing sperm immobilizing antibodies, but not by normal women's sera or several other sperm immobilizing MAbs to human sperm. These results suggest that the sperm immobilizing antibody in women's sera is directed against the 3-O-sulfogalactose residue of seminolipid on the sperm membrane."} {"id": "PMID:1280686", "title": "Light and electron microscopic immunolocalization of sperm proteins identified by monoclonal antibodies from the World Health Organization Task Force on Sperm Antigens.", "content": "Sperm antigens recognized by monoclonal antibodies (mAbs), S19, S69, S71, S72 and S77 submitted to the World Health Organization (WHO)-Sponsored Sperm Monoclonal Antibody Workshops were immunolocalized by light (LM) and transmission electron microscopy (TEM). S19 was surface reactive while mAbs S69, S71, S72 and S77 recognized internal antigens. Indirect immunofluorescence staining of permeabilized sperm with the mAbs revealed that S69 recognized an internal tail antigen, while S71, S72 and S77 recognized acrosomal proteins. Preservation of immunoreactivity after fixation in various combinations of glutaraldehyde, paraformaldehyde and tannic acid was evaluated for mAbs S69 to S77 using immunofluorescence microscopy. The epitopes recognized by these mAbs were adversely affected by these fixatives; therefore, pre-embedding immunogold staining was employed, prior to fixation, osmication, dehydration and embedding. Using this approach, the antigen recognized by mAb S19 was found associated with the plasmalemma of the head and tail of intact sperm. Monoclonal antibody S69 localized to the fibrous sheath. The mAbs S71, S72 and S77, which required sperm permeabilization to expose their acrosomal locus by LM, did not immunoreact with the plasmalemma at the TEM level. Ultrastructural examination of acrosome-reacted sperm revealed the localization of S71 and S77 on the inner and outer acrosomal membranes and with acrosomal matrix. The S72 antigen was associated with the inner and outer acrosomal membranes.", "contents": "Light and electron microscopic immunolocalization of sperm proteins identified by monoclonal antibodies from the World Health Organization Task Force on Sperm Antigens. Sperm antigens recognized by monoclonal antibodies (mAbs), S19, S69, S71, S72 and S77 submitted to the World Health Organization (WHO)-Sponsored Sperm Monoclonal Antibody Workshops were immunolocalized by light (LM) and transmission electron microscopy (TEM). S19 was surface reactive while mAbs S69, S71, S72 and S77 recognized internal antigens. Indirect immunofluorescence staining of permeabilized sperm with the mAbs revealed that S69 recognized an internal tail antigen, while S71, S72 and S77 recognized acrosomal proteins. Preservation of immunoreactivity after fixation in various combinations of glutaraldehyde, paraformaldehyde and tannic acid was evaluated for mAbs S69 to S77 using immunofluorescence microscopy. The epitopes recognized by these mAbs were adversely affected by these fixatives; therefore, pre-embedding immunogold staining was employed, prior to fixation, osmication, dehydration and embedding. Using this approach, the antigen recognized by mAb S19 was found associated with the plasmalemma of the head and tail of intact sperm. Monoclonal antibody S69 localized to the fibrous sheath. The mAbs S71, S72 and S77, which required sperm permeabilization to expose their acrosomal locus by LM, did not immunoreact with the plasmalemma at the TEM level. Ultrastructural examination of acrosome-reacted sperm revealed the localization of S71 and S77 on the inner and outer acrosomal membranes and with acrosomal matrix. The S72 antigen was associated with the inner and outer acrosomal membranes."} {"id": "PMID:1280684", "title": "Sustained food vacuole formation by axenic Paramecium tetraurelia and the inhibition of membrane recycling by Alcian Blue.", "content": "It is believed that the uptake mechanism of some nutrients by Paramecium tetraurelia primarily involves transport through the cell surface, whereas the uptake of other compounds appears to be restricted to bulk transport during food vacuole (phagosome) formation. In this study, we established that, in axenically grown cells, food vacuole formation occurred at continuous rates over long periods. This information allows quantitation of the volume of media taken up by bulk transport. India ink and latex beads were shown to be inert food vacuole markers and carmine was found to have an initial stimulatory effect on phagosome formation rates. Cultures grown for 3.5 h or longer with the glycocalyx stain Alcian Blue, contained only three phagosomes/cell, whereas cells cultured with the other markers contained 15 phagosomes/cell. Electron microscopy of fecal material that accumulated at the bottom of Alcian Blue-grown cells demonstrated the presence of membranes, suggesting that the vacuolar membrane was eliminated during defecation. Neither cell lysis nor the formation of autophagous vacuoles was detected in Alcian Blue-grown cells, indicating that the stain was not cytotoxic at the concentrations used. Thus it appeared that the binding of Alcian Blue to the digestive vacuole membrane resulted in a loss of the vacuole membranes from the cell which reduced the amount of membranes retrieved and recycled and hence eventually reduced the rate of phagosome formation. Alcian Blue-treated cultures exhibited decreased rate of growth and final density, which is consistent with a decrease in bulk transport of nutrients resulting from reduced membranes of digestive cycle organelles available in the cell.", "contents": "Sustained food vacuole formation by axenic Paramecium tetraurelia and the inhibition of membrane recycling by Alcian Blue. It is believed that the uptake mechanism of some nutrients by Paramecium tetraurelia primarily involves transport through the cell surface, whereas the uptake of other compounds appears to be restricted to bulk transport during food vacuole (phagosome) formation. In this study, we established that, in axenically grown cells, food vacuole formation occurred at continuous rates over long periods. This information allows quantitation of the volume of media taken up by bulk transport. India ink and latex beads were shown to be inert food vacuole markers and carmine was found to have an initial stimulatory effect on phagosome formation rates. Cultures grown for 3.5 h or longer with the glycocalyx stain Alcian Blue, contained only three phagosomes/cell, whereas cells cultured with the other markers contained 15 phagosomes/cell. Electron microscopy of fecal material that accumulated at the bottom of Alcian Blue-grown cells demonstrated the presence of membranes, suggesting that the vacuolar membrane was eliminated during defecation. Neither cell lysis nor the formation of autophagous vacuoles was detected in Alcian Blue-grown cells, indicating that the stain was not cytotoxic at the concentrations used. Thus it appeared that the binding of Alcian Blue to the digestive vacuole membrane resulted in a loss of the vacuole membranes from the cell which reduced the amount of membranes retrieved and recycled and hence eventually reduced the rate of phagosome formation. Alcian Blue-treated cultures exhibited decreased rate of growth and final density, which is consistent with a decrease in bulk transport of nutrients resulting from reduced membranes of digestive cycle organelles available in the cell."} {"id": "PMID:1280687", "title": "Unexplained positive/elevated maternal serum alpha-fetoprotein associated with placenta increta. A case report.", "content": "Maternal serum alpha-fetoprotein (MSAFP) is a regularly utilized antenatal screening test for the identification of pregnancies at increased risk for a variety of genetic and nongenetic abnormalities. Complete mid-trimester evaluation of the patient with a positive screening test may fail to reveal an etiology for a positive MSAFP value. This case report concerns an unexplained positive/elevated MSAFP screening test for a patient found at delivery to have abnormal placentation.", "contents": "Unexplained positive/elevated maternal serum alpha-fetoprotein associated with placenta increta. A case report. Maternal serum alpha-fetoprotein (MSAFP) is a regularly utilized antenatal screening test for the identification of pregnancies at increased risk for a variety of genetic and nongenetic abnormalities. Complete mid-trimester evaluation of the patient with a positive screening test may fail to reveal an etiology for a positive MSAFP value. This case report concerns an unexplained positive/elevated MSAFP screening test for a patient found at delivery to have abnormal placentation."} {"id": "PMID:1280688", "title": "Nitric oxide synthase is critical in mediating basal forebrain regulation of cortical cerebral circulation.", "content": "This study sought to determine whether the activity of nitric oxide synthase (NOS) is an important physiological link required to mediate increases in cortical cerebral blood flow (CBF) elicited by electrical microstimulation of the basal forebrain (BF). Changes in cortical CBF were assessed in urethane anesthetized rats using laser-Doppler flowmetry. Microstimulation of the BF elicited stimulus-locked increases in CBF that were dependent on frequency and current intensity (up to 280% of control at 50 Hz). Infusion of the potent NOS inhibitor NG-nitro-L-arginine (L-NNA) resulted in significant dose-related reductions in the BF-elicited response at 50 Hz (3.75-60 mg/kg, i.v.), significant elevation in resting mean arterial pressure (MAP) from 106 to 160 mmHg, and modest 21% reductions in resting CBF. The stereoisomer NG-nitro-D-arginine (D-NNA) was without any effect on CBF, although at higher concentrations MAP was elevated to levels comparable to those obtained with L-NNA. Infusion of arginase was also without effect on resting or BF-elicited CBF responses. In contrast, L-arginine (100-400 mg/kg, i.v.) significantly potentiated the BF-elicited response up to an additional 38%, without affecting resting CBF or MAP. This study suggests that NO, or a related nitroso precursor formed by NOS, has a critical role in mediating regulation of cortical CBF by BF neurons.", "contents": "Nitric oxide synthase is critical in mediating basal forebrain regulation of cortical cerebral circulation. This study sought to determine whether the activity of nitric oxide synthase (NOS) is an important physiological link required to mediate increases in cortical cerebral blood flow (CBF) elicited by electrical microstimulation of the basal forebrain (BF). Changes in cortical CBF were assessed in urethane anesthetized rats using laser-Doppler flowmetry. Microstimulation of the BF elicited stimulus-locked increases in CBF that were dependent on frequency and current intensity (up to 280% of control at 50 Hz). Infusion of the potent NOS inhibitor NG-nitro-L-arginine (L-NNA) resulted in significant dose-related reductions in the BF-elicited response at 50 Hz (3.75-60 mg/kg, i.v.), significant elevation in resting mean arterial pressure (MAP) from 106 to 160 mmHg, and modest 21% reductions in resting CBF. The stereoisomer NG-nitro-D-arginine (D-NNA) was without any effect on CBF, although at higher concentrations MAP was elevated to levels comparable to those obtained with L-NNA. Infusion of arginase was also without effect on resting or BF-elicited CBF responses. In contrast, L-arginine (100-400 mg/kg, i.v.) significantly potentiated the BF-elicited response up to an additional 38%, without affecting resting CBF or MAP. This study suggests that NO, or a related nitroso precursor formed by NOS, has a critical role in mediating regulation of cortical CBF by BF neurons."} {"id": "PMID:1280689", "title": "DM20 mRNA splice product of the myelin proteolipid protein gene is expressed in the murine heart.", "content": "Northern blot analysis of poly A(+) RNA isolated from mouse heart revealed the expression of 3.3 and 2.4 kb mRNAs that hybridized with a cDNA for the mouse proteolipid protein (PLP). In order to examine the relationship of these RNAs to the myelin PLP/DM20 mRNAs, a mouse heart cDNA library was prepared and screened with a mouse PLP cDNA. A cDNA was isolated, sequenced, and found to encode the DM20 variant of PLP. Polymerase chain reaction (PCR) analysis of heart cDNA with three sets of primers confirmed the presence of DM20 mRNA in mouse heart and indicated that it is the major splice product of the PLP gene expressed in that tissue. In situ hybridization localized the expression of the DM20 mRNA to the myocardial cells. Northern blot analysis indicated that expression of the DM20 mRNA is developmentally regulated in the murine heart, increasing significantly in concentration after 12 days postpartum. Northern analysis also revealed the expression of the DM20 mRNA in the hearts of the jimpy and quaking mutants. These results indicate that the PLP gene is expressed in tissues other than brain and support the concept that products of the PLP gene may have some biological role other than as structural components of myelin.", "contents": "DM20 mRNA splice product of the myelin proteolipid protein gene is expressed in the murine heart. Northern blot analysis of poly A(+) RNA isolated from mouse heart revealed the expression of 3.3 and 2.4 kb mRNAs that hybridized with a cDNA for the mouse proteolipid protein (PLP). In order to examine the relationship of these RNAs to the myelin PLP/DM20 mRNAs, a mouse heart cDNA library was prepared and screened with a mouse PLP cDNA. A cDNA was isolated, sequenced, and found to encode the DM20 variant of PLP. Polymerase chain reaction (PCR) analysis of heart cDNA with three sets of primers confirmed the presence of DM20 mRNA in mouse heart and indicated that it is the major splice product of the PLP gene expressed in that tissue. In situ hybridization localized the expression of the DM20 mRNA to the myocardial cells. Northern blot analysis indicated that expression of the DM20 mRNA is developmentally regulated in the murine heart, increasing significantly in concentration after 12 days postpartum. Northern analysis also revealed the expression of the DM20 mRNA in the hearts of the jimpy and quaking mutants. These results indicate that the PLP gene is expressed in tissues other than brain and support the concept that products of the PLP gene may have some biological role other than as structural components of myelin."} {"id": "PMID:1280690", "title": "Endogenous aFGF expression and cellular changes after a demyelinating lesion in the spinal cord of adult normal mice: immunohistochemical study.", "content": "Fibroblast growth factors (FGFs) are known to act on glial cells in vitro. At the present time, their involvement in the remyelinating process of the adult central nervous system (CNS) is still unknown. In the present study, using immunohistochemistry (IHC), we investigated the evolution in time and space of acidic FGF (aFGF) expression and CNS cell changes occurring after a chemically induced demyelinating lesion. In a first early period, aFGF immunostaining was shown to decrease around the demyelinated area. A dramatic increase was then observed and was accompanied by an increase of cell density around and inside the lesion. This was correlated with the beginning of remyelination. Late after demyelination, while remyelination was still in progress, aFGF immunostaining of the lesion and unlesioned spinal cord were comparable. A role of aFGF in remyelination is proposed.", "contents": "Endogenous aFGF expression and cellular changes after a demyelinating lesion in the spinal cord of adult normal mice: immunohistochemical study. Fibroblast growth factors (FGFs) are known to act on glial cells in vitro. At the present time, their involvement in the remyelinating process of the adult central nervous system (CNS) is still unknown. In the present study, using immunohistochemistry (IHC), we investigated the evolution in time and space of acidic FGF (aFGF) expression and CNS cell changes occurring after a chemically induced demyelinating lesion. In a first early period, aFGF immunostaining was shown to decrease around the demyelinated area. A dramatic increase was then observed and was accompanied by an increase of cell density around and inside the lesion. This was correlated with the beginning of remyelination. Late after demyelination, while remyelination was still in progress, aFGF immunostaining of the lesion and unlesioned spinal cord were comparable. A role of aFGF in remyelination is proposed."} {"id": "PMID:1280691", "title": "Mitotic potential of adult rat oligodendrocytes in culture.", "content": "The proliferation of adult oligodendrocytes (OLGs) was examined in response to membrane bound and soluble mitogens. OLGs were isolated according to Vick, et al., J Neurosci Res 25:524-534, 1990, and co-cultured with dorsal root ganglia (DRGs). Less than 5% of the total cells incorporated a 48 hr pulse of 3H thymidine during the first 4 days of co-culture. From day 4 to day 6 there was a dramatic increase in proliferation which reached a plateau at 40% and gradually decreased to 25% from days 10 to 20 of co-culture. Axolemma-enriched fractions (AEF) were weak mitogens for OLGs (less than 5% proliferation after 7 days of stimulation), however, heparin extracts of AEF were five-fold more mitogenic than the AEF from which they were derived. Basic and acidic fibroblast growth factor were effective mitogens for the adult OLGs (labelling indices of 28% and 12%, respectively) provided that the cells were treated for 7 days with the growth factor and that the cells had been in culture for at least 14 days. Other soluble growth factors (IL-2 and PDGF) gave no mitotic response. We conclude that adult OLGs are mitotically responsive to mitogens provided that (1) the adult OLG has been cultured for sufficient time (14 days, acidic or basic fibroblast growth factor); (2) the axonal mitogen is allowed to interact with the OLG for a sufficient time (neuritic mitogen); and (3) the axonal mitogen is presented to the OLG in an activated form (AEF-heparin extract).", "contents": "Mitotic potential of adult rat oligodendrocytes in culture. The proliferation of adult oligodendrocytes (OLGs) was examined in response to membrane bound and soluble mitogens. OLGs were isolated according to Vick, et al., J Neurosci Res 25:524-534, 1990, and co-cultured with dorsal root ganglia (DRGs). Less than 5% of the total cells incorporated a 48 hr pulse of 3H thymidine during the first 4 days of co-culture. From day 4 to day 6 there was a dramatic increase in proliferation which reached a plateau at 40% and gradually decreased to 25% from days 10 to 20 of co-culture. Axolemma-enriched fractions (AEF) were weak mitogens for OLGs (less than 5% proliferation after 7 days of stimulation), however, heparin extracts of AEF were five-fold more mitogenic than the AEF from which they were derived. Basic and acidic fibroblast growth factor were effective mitogens for the adult OLGs (labelling indices of 28% and 12%, respectively) provided that the cells were treated for 7 days with the growth factor and that the cells had been in culture for at least 14 days. Other soluble growth factors (IL-2 and PDGF) gave no mitotic response. We conclude that adult OLGs are mitotically responsive to mitogens provided that (1) the adult OLG has been cultured for sufficient time (14 days, acidic or basic fibroblast growth factor); (2) the axonal mitogen is allowed to interact with the OLG for a sufficient time (neuritic mitogen); and (3) the axonal mitogen is presented to the OLG in an activated form (AEF-heparin extract)."} {"id": "PMID:1280692", "title": "Developmental expression of major myelin protein genes in the CNS of X-linked hypomyelinating mutant rumpshaker.", "content": "Rumpshaker (rsh) is an X-linked mutation causing hypomyelination of the CNS of mice and has recently been identified as an allele of jimpy (jp). The mutation (known as jprsh) differs in several respects from other X-linked myelin mutants, including jp, in that mice have normal longevity, oligodendrocyte numbers are not decreased, and cell death is not a feature. Myelin sheaths are deficient in immunostainable PLP protein. The present study examines the developmental expression of the major myelin protein genes and translatability of PLP and MBP mRNA. Differences between the spinal cord and brain of mutants are evident in that mRNA levels are more markedly decreased in the brain. Protein levels are severely reduced in both locations and to a proportionately greater extent than the mRNA, particularly in the spinal cord where PLP RNA and protein are approximately 80% and 10-20%, respectively, of age-matched wild type mice. DM-20 protein, the other major product of the PLP gene, is disproportionately expressed in rumpshaker as is a 10 kDa proteolipid. In vitro translation studies indicate a marked decrease in PLP translation products from mutant RNA. There is no deficiency in the number of PLP mRNA-expressing oligodendrocytes although the abundance per cell is reduced. The data suggest that the phenotypic effects of the mutation may be associated with reduced translation of major myelin proteins, in particular PLP and its incorporation into compact myelin. However, the mutation is compatible with survival of oligodendrocytes and their differentiation to the stage of expressing PLP/DM-20 mRNA.", "contents": "Developmental expression of major myelin protein genes in the CNS of X-linked hypomyelinating mutant rumpshaker. Rumpshaker (rsh) is an X-linked mutation causing hypomyelination of the CNS of mice and has recently been identified as an allele of jimpy (jp). The mutation (known as jprsh) differs in several respects from other X-linked myelin mutants, including jp, in that mice have normal longevity, oligodendrocyte numbers are not decreased, and cell death is not a feature. Myelin sheaths are deficient in immunostainable PLP protein. The present study examines the developmental expression of the major myelin protein genes and translatability of PLP and MBP mRNA. Differences between the spinal cord and brain of mutants are evident in that mRNA levels are more markedly decreased in the brain. Protein levels are severely reduced in both locations and to a proportionately greater extent than the mRNA, particularly in the spinal cord where PLP RNA and protein are approximately 80% and 10-20%, respectively, of age-matched wild type mice. DM-20 protein, the other major product of the PLP gene, is disproportionately expressed in rumpshaker as is a 10 kDa proteolipid. In vitro translation studies indicate a marked decrease in PLP translation products from mutant RNA. There is no deficiency in the number of PLP mRNA-expressing oligodendrocytes although the abundance per cell is reduced. The data suggest that the phenotypic effects of the mutation may be associated with reduced translation of major myelin proteins, in particular PLP and its incorporation into compact myelin. However, the mutation is compatible with survival of oligodendrocytes and their differentiation to the stage of expressing PLP/DM-20 mRNA."} {"id": "PMID:1280693", "title": "Isolation of activated adult Schwann cells and a spontaneously immortal Schwann cell clone.", "content": "Successful mammalian peripheral nerve regeneration is dependent on activated Schwann cells. Schwann cells facilitate neuronal regrowth through the production of tropic cell membrane molecules, neurotrophins, and extracellular matrix components. To better understand Schwann cell function in the regenerating nerve, we have designed a method of isolating proliferating adult Schwann cells from the injured rat sciatic nerve. Relying on the mitotic signal that is present after a crush injury, we can obtain sufficient numbers of dividing Schwann cells within one week of initial culture. A spontaneously immortal Schwann cell clone (iSC) was observed in and isolated from one of these primary cultures. These cells were transformed at a time of maximal Schwann cell activation in response to injury. Both the primary Schwann cells and the iSC have been characterized as Schwann cells by morphology, immunohistochemistry and gene expression.", "contents": "Isolation of activated adult Schwann cells and a spontaneously immortal Schwann cell clone. Successful mammalian peripheral nerve regeneration is dependent on activated Schwann cells. Schwann cells facilitate neuronal regrowth through the production of tropic cell membrane molecules, neurotrophins, and extracellular matrix components. To better understand Schwann cell function in the regenerating nerve, we have designed a method of isolating proliferating adult Schwann cells from the injured rat sciatic nerve. Relying on the mitotic signal that is present after a crush injury, we can obtain sufficient numbers of dividing Schwann cells within one week of initial culture. A spontaneously immortal Schwann cell clone (iSC) was observed in and isolated from one of these primary cultures. These cells were transformed at a time of maximal Schwann cell activation in response to injury. Both the primary Schwann cells and the iSC have been characterized as Schwann cells by morphology, immunohistochemistry and gene expression."} {"id": "PMID:1280694", "title": "Developmental changes in nerve growth factor level in rat serum.", "content": "In serum, nerve growth factor (NGF) forms a complex with alpha 2-macroglobulin (alpha 2M), which formation inhibits the immunoreactivity between NGF and its antibodies. For measuring the serum level of NGF, it is thus necessary to liberate NGF from the NGF-alpha 2M complex and prevent reformation of such complex. The pretreatment of rat serum with 1 M guanidine hydrochloride for a few hours and operation of the enzyme immunoassay (EIA) in the presence of guanidine hydrochloride provided a reliable means for determination of the NGF level in serum. By this procedure we followed the serum NGF level in rats developmentally. It increased from prenatal day 2 to postnatal day 5 and decreased slightly at postnatal week 3, thereafter remaining constant throughout adulthood. In pregnant rats, the NGF level in serum increased threefold to fivefold before birth and then decreased rapidly. These data suggest that serum NGF level may reflect the demand for this molecule during establishment of the peripheral nervous system.", "contents": "Developmental changes in nerve growth factor level in rat serum. In serum, nerve growth factor (NGF) forms a complex with alpha 2-macroglobulin (alpha 2M), which formation inhibits the immunoreactivity between NGF and its antibodies. For measuring the serum level of NGF, it is thus necessary to liberate NGF from the NGF-alpha 2M complex and prevent reformation of such complex. The pretreatment of rat serum with 1 M guanidine hydrochloride for a few hours and operation of the enzyme immunoassay (EIA) in the presence of guanidine hydrochloride provided a reliable means for determination of the NGF level in serum. By this procedure we followed the serum NGF level in rats developmentally. It increased from prenatal day 2 to postnatal day 5 and decreased slightly at postnatal week 3, thereafter remaining constant throughout adulthood. In pregnant rats, the NGF level in serum increased threefold to fivefold before birth and then decreased rapidly. These data suggest that serum NGF level may reflect the demand for this molecule during establishment of the peripheral nervous system."} {"id": "PMID:1280695", "title": "Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) in rats. 1. Acute and subchronic toxicity.", "content": "The acute and subchronic toxicity studies on 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) were conducted using male and female Wistar rats. In acute toxicity test, the LD50 values were estimated to be greater than 10 g/kg BW by oral and intraperitoneal administration in each sex. In subchronic toxicity test, groups of 10 rats of each sex were fed a diet containing 0.2, 1.0 or 5.0% of MBEBP and examined at 4 and 12 weeks. Body weight gain was significantly depressed at doses of 1.0 and 5.0% in both sexes, but the depression in the 1.0% group was severer than that in the 5.0% group in males. Hematological analysis showed slight but significant decrease of hemoglobin in the 1.0 and 5.0% groups of both sexes. Urine analysis showed no remarkable changes in all treated rats of both sexes. In biochemical analysis of serum, decrease of triglyceride level and cholinesterase activity, and increase of amylase activity were observed in treated rats. Histopathologically, testicular atrophy and decrease of spermatogenesis were observed in male rats fed 1.0 or 5.0% MBEBP for 4 and 12 weeks and vacuolization of parathyroid gland cells was observed in female rats fed 1.0 and 5.0% MBEBP for 12 weeks. In subchronic test, the lowest observable adverse effect levels for MBEBP toxicity were estimated to be 171 mg/kg BW/day in male rats and 180 mg/kg BW/day in female rats.", "contents": "Toxicity studies of a synthetic antioxidant, 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) in rats. 1. Acute and subchronic toxicity. The acute and subchronic toxicity studies on 2,2'-methylenebis (4-ethyl-6-tert-butylphenol) (MBEBP) were conducted using male and female Wistar rats. In acute toxicity test, the LD50 values were estimated to be greater than 10 g/kg BW by oral and intraperitoneal administration in each sex. In subchronic toxicity test, groups of 10 rats of each sex were fed a diet containing 0.2, 1.0 or 5.0% of MBEBP and examined at 4 and 12 weeks. Body weight gain was significantly depressed at doses of 1.0 and 5.0% in both sexes, but the depression in the 1.0% group was severer than that in the 5.0% group in males. Hematological analysis showed slight but significant decrease of hemoglobin in the 1.0 and 5.0% groups of both sexes. Urine analysis showed no remarkable changes in all treated rats of both sexes. In biochemical analysis of serum, decrease of triglyceride level and cholinesterase activity, and increase of amylase activity were observed in treated rats. Histopathologically, testicular atrophy and decrease of spermatogenesis were observed in male rats fed 1.0 or 5.0% MBEBP for 4 and 12 weeks and vacuolization of parathyroid gland cells was observed in female rats fed 1.0 and 5.0% MBEBP for 12 weeks. In subchronic test, the lowest observable adverse effect levels for MBEBP toxicity were estimated to be 171 mg/kg BW/day in male rats and 180 mg/kg BW/day in female rats."} {"id": "PMID:1280697", "title": "[Basic and clinical evaluation of the new kit for detection of serum prostate specific antigen (PSA)].", "content": "BALL-ELSA PSA is a monoclonal radioimmunometric assay kit for detection of serum prostate specific antigen (PSA) developed and generally used in Europe. Basic and clinical study of the kit was performed for evaluation of it's utility in Japanese patients. The sera from 56 patients with benign prostatic hyperplasia (BPH), 35 patients with prostate cancer (PCA) and 18 normal males were examined. Other kits such as EIKEN PSA and EIKEN PAP (prostatic acid phosphatase) were also evaluated in same sera. The results of the range in the measurement, within-assay error, between-assay error, dilution test, recovery test and others were well satisfied. In our clinical study, mean + 2SD of serum PSA values in normal males was 2.57 ng/ml. Serum PSA values determined by the two RIA kits, BALL-ELSA and EIKEN, showed a good correlation (r = 0.9909), but the BALL-ELSA PSA kit yielded values about 2.4 times higher than the EIKEN PSA kit on the same sample. We think that the difference might be largely due to differences in assigned PSA calibrators and diluents between the assay kits. Further investigations and discussions were expected on this point. In our study, the most suitable cut-off level for distinguishing PCA from BPH in BALL-ELSA PSA kit was 10.0 ng/ml.", "contents": "[Basic and clinical evaluation of the new kit for detection of serum prostate specific antigen (PSA)]. BALL-ELSA PSA is a monoclonal radioimmunometric assay kit for detection of serum prostate specific antigen (PSA) developed and generally used in Europe. Basic and clinical study of the kit was performed for evaluation of it's utility in Japanese patients. The sera from 56 patients with benign prostatic hyperplasia (BPH), 35 patients with prostate cancer (PCA) and 18 normal males were examined. Other kits such as EIKEN PSA and EIKEN PAP (prostatic acid phosphatase) were also evaluated in same sera. The results of the range in the measurement, within-assay error, between-assay error, dilution test, recovery test and others were well satisfied. In our clinical study, mean + 2SD of serum PSA values in normal males was 2.57 ng/ml. Serum PSA values determined by the two RIA kits, BALL-ELSA and EIKEN, showed a good correlation (r = 0.9909), but the BALL-ELSA PSA kit yielded values about 2.4 times higher than the EIKEN PSA kit on the same sample. We think that the difference might be largely due to differences in assigned PSA calibrators and diluents between the assay kits. Further investigations and discussions were expected on this point. In our study, the most suitable cut-off level for distinguishing PCA from BPH in BALL-ELSA PSA kit was 10.0 ng/ml."} {"id": "PMID:1280698", "title": "Expression of nitric oxide synthase in kidney macula densa cells.", "content": "The distribution of nitric oxide synthase (NOS), the enzyme by which NO is generated from L-arginine, was investigated in rat kidney. The indirect immunofluorescence technique using a polyclonal antibody against type I NOS was applied, followed by the histochemical NADPH diaphorase staining technique on the same sections in order to demonstrate the enzymatic activity of NOS. Macula densa cells were strongly stained by both techniques, demonstrating abundant NOS in the cytoplasm of these cells. In addition, these findings were confirmed by nonradioactive in situ hybridization, thus demonstrating the corresponding messenger RNA in macula densa cells as well. Our findings provide the morphological basis for a possible role of NO as a mediator substance in signal transfer from distal tubular fluid to glomerular arterioles.", "contents": "Expression of nitric oxide synthase in kidney macula densa cells. The distribution of nitric oxide synthase (NOS), the enzyme by which NO is generated from L-arginine, was investigated in rat kidney. The indirect immunofluorescence technique using a polyclonal antibody against type I NOS was applied, followed by the histochemical NADPH diaphorase staining technique on the same sections in order to demonstrate the enzymatic activity of NOS. Macula densa cells were strongly stained by both techniques, demonstrating abundant NOS in the cytoplasm of these cells. In addition, these findings were confirmed by nonradioactive in situ hybridization, thus demonstrating the corresponding messenger RNA in macula densa cells as well. Our findings provide the morphological basis for a possible role of NO as a mediator substance in signal transfer from distal tubular fluid to glomerular arterioles."} {"id": "PMID:1280699", "title": "Vascular cell adhesion molecule-1 (VCAM-1) expression in murine lupus nephritis.", "content": "Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface protein which mediates adherence of inflammatory cells to target cells by binding with the beta 1-integrin ligand Very Late Antigen-4 (VLA-4) on leukocytes. The expression of VCAM-1 was investigated in a murine model of lupus nephritis, the autoimmune MRL/lpr mouse. Compared with normal mice, MRL/lpr kidneys show increased VCAM-1 expression not only in the endothelium, but also in cortical tubules and glomeruli. Increased steady-state VCAM-1 mRNA levels (approximately 3 kB) are detected in the kidney of nephritic MRL/lpr mice. Two additional transcripts (approximately 2 and approximately 1.8 kB) are present in autoimmune MRL/lpr but not in normal mice. Like ICAM-1, VCAM-1 is also upregulated in vitro in renal cortical tubular and mesangial cells by TNF-alpha, IL-1 and IFN-gamma. T cell and macrophage cell lines adhere to TNF-alpha stimulated tubular epithelial cells by using the VCAM-1/VLA-4 and the ICAM-1/LFA-1 binding pairs. Kidney tissue sections from nephritic MRL/lpr also display increased adhesiveness for T cell and macrophage cell lines, and for MRL/lpr lymph node cells when compared with normal kidney sections. This enhanced adhesiveness of MRL/lpr kidney tissue is inhibited with monoclonal antibodies targeting the VCAM-1 and ICAM-1 molecules. Thus, VCAM-1 and ICAM-1 function as renal parenchymal adhesion molecules and mediate the adherence of pathogenic inflammatory cells in murine lupus nephritis.", "contents": "Vascular cell adhesion molecule-1 (VCAM-1) expression in murine lupus nephritis. Vascular cell adhesion molecule-1 (VCAM-1) is a cell surface protein which mediates adherence of inflammatory cells to target cells by binding with the beta 1-integrin ligand Very Late Antigen-4 (VLA-4) on leukocytes. The expression of VCAM-1 was investigated in a murine model of lupus nephritis, the autoimmune MRL/lpr mouse. Compared with normal mice, MRL/lpr kidneys show increased VCAM-1 expression not only in the endothelium, but also in cortical tubules and glomeruli. Increased steady-state VCAM-1 mRNA levels (approximately 3 kB) are detected in the kidney of nephritic MRL/lpr mice. Two additional transcripts (approximately 2 and approximately 1.8 kB) are present in autoimmune MRL/lpr but not in normal mice. Like ICAM-1, VCAM-1 is also upregulated in vitro in renal cortical tubular and mesangial cells by TNF-alpha, IL-1 and IFN-gamma. T cell and macrophage cell lines adhere to TNF-alpha stimulated tubular epithelial cells by using the VCAM-1/VLA-4 and the ICAM-1/LFA-1 binding pairs. Kidney tissue sections from nephritic MRL/lpr also display increased adhesiveness for T cell and macrophage cell lines, and for MRL/lpr lymph node cells when compared with normal kidney sections. This enhanced adhesiveness of MRL/lpr kidney tissue is inhibited with monoclonal antibodies targeting the VCAM-1 and ICAM-1 molecules. Thus, VCAM-1 and ICAM-1 function as renal parenchymal adhesion molecules and mediate the adherence of pathogenic inflammatory cells in murine lupus nephritis."} {"id": "PMID:1280700", "title": "Demonstration of plasma proteinase inhibitors in beta 2-microglobulin amyloid deposits.", "content": "beta 2-microglobulin-related amyloidosis (A beta 2M) represents a frequent complication in long-term dialysis patients. Although the pathogenetic mechanism has yet to be fully understood, it is known that amyloid fibrils usually consist of intact molecules of beta 2-microglobulin (beta 2m). Plasma proteinase inhibitors (PPI) are a broad family of glycoproteins with the function of eliminating unwanted proteolysis of serine proteases. Their role in amyloidogenesis has become a subject of intense discussion, especially since the recent identification of alpha 1-antichymotrypsin in the beta-protein amyloid deposits of Alzheimer's disease. We evaluated immunohistochemically and biochemically the presence and distribution of several PPIs (alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, antithrombin III, alpha 2-macroglobulin and tissue inhibitor metalloproteinase) and amyloid P component in A beta 2M deposits in osteo-articular and visceral tissues from dialysis patients with amyloidosis, as well as two carpal tunnel synovia from non-dialysis patients and one Alzheimer's brain as controls. The immunohistochemical study demonstrated that all but one (anti-alpha 1-antichymotrypsin) of the PPI antibodies tested showed varying degrees of positive reaction against A beta 2M deposits. All the antibodies (including anti-alpha 1-antichymotrypsin) also reacted to some extent with other non-amyloid visceral and connective tissue elements diffusely and/or selectively. Among them, only the reaction of anti-amyloid P component had significantly distinctive localization to A beta 2M deposits, which were identified in adjacent serial sections by Congo red staining and immunohistochemical reaction against anti-beta 2m.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Demonstration of plasma proteinase inhibitors in beta 2-microglobulin amyloid deposits. beta 2-microglobulin-related amyloidosis (A beta 2M) represents a frequent complication in long-term dialysis patients. Although the pathogenetic mechanism has yet to be fully understood, it is known that amyloid fibrils usually consist of intact molecules of beta 2-microglobulin (beta 2m). Plasma proteinase inhibitors (PPI) are a broad family of glycoproteins with the function of eliminating unwanted proteolysis of serine proteases. Their role in amyloidogenesis has become a subject of intense discussion, especially since the recent identification of alpha 1-antichymotrypsin in the beta-protein amyloid deposits of Alzheimer's disease. We evaluated immunohistochemically and biochemically the presence and distribution of several PPIs (alpha 1-proteinase inhibitor, alpha 1-antichymotrypsin, antithrombin III, alpha 2-macroglobulin and tissue inhibitor metalloproteinase) and amyloid P component in A beta 2M deposits in osteo-articular and visceral tissues from dialysis patients with amyloidosis, as well as two carpal tunnel synovia from non-dialysis patients and one Alzheimer's brain as controls. The immunohistochemical study demonstrated that all but one (anti-alpha 1-antichymotrypsin) of the PPI antibodies tested showed varying degrees of positive reaction against A beta 2M deposits. All the antibodies (including anti-alpha 1-antichymotrypsin) also reacted to some extent with other non-amyloid visceral and connective tissue elements diffusely and/or selectively. Among them, only the reaction of anti-amyloid P component had significantly distinctive localization to A beta 2M deposits, which were identified in adjacent serial sections by Congo red staining and immunohistochemical reaction against anti-beta 2m.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280701", "title": "Adhesion of rat glomerular epithelial cells to extracellular matrices: role of beta 1 integrins.", "content": "Glomerular epithelial cells (GEC) maintain glomerular permselectivity and are a target of immunological glomerular injury, which may lead to proliferation or detachment from extracellular matrix (ECM). We studied adhesion mechanisms in rat GEC in culture, focusing on adhesion molecules of the beta 1 integrin family. At early time points (1 hr after plating of cells into culture wells that had been pre-incubated with purified ECM proteins), adhesion of GEC to collagen I, collagen IV, laminin, and fibronectin was inhibited with anti-beta 1 integrin antibody. The peptide RGDS inhibited adhesion to fibronectin and laminin. Immunoprecipitation studies demonstrated the presence of alpha 2, alpha 3, and beta 1 integrins; the alpha 1, alpha 4, alpha 5, alpha 6, alpha v, and beta 3 subunits were undetectable. Adhesion to all ECM proteins was dependent on divalent cations, but the effects of individual cations varied among substrata. In rat GEC, alpha 2 beta 1 and/or alpha 3 beta 1 integrins appear to mediate adhesion to collagen I, collagen IV, and laminin. The alpha 3 beta 1 integrin is also the likely receptor for fibronectin, interacting through an RGD binding site. Furthermore, single integrins or combinations of integrins appear to have distinct ligand-binding functions that are differentially regulated by divalent cations. Characterization of GEC adhesion molecules may facilitate the understanding of mechanisms of glomerular development, and cell detachment or proliferation in immune glomerular injury.", "contents": "Adhesion of rat glomerular epithelial cells to extracellular matrices: role of beta 1 integrins. Glomerular epithelial cells (GEC) maintain glomerular permselectivity and are a target of immunological glomerular injury, which may lead to proliferation or detachment from extracellular matrix (ECM). We studied adhesion mechanisms in rat GEC in culture, focusing on adhesion molecules of the beta 1 integrin family. At early time points (1 hr after plating of cells into culture wells that had been pre-incubated with purified ECM proteins), adhesion of GEC to collagen I, collagen IV, laminin, and fibronectin was inhibited with anti-beta 1 integrin antibody. The peptide RGDS inhibited adhesion to fibronectin and laminin. Immunoprecipitation studies demonstrated the presence of alpha 2, alpha 3, and beta 1 integrins; the alpha 1, alpha 4, alpha 5, alpha 6, alpha v, and beta 3 subunits were undetectable. Adhesion to all ECM proteins was dependent on divalent cations, but the effects of individual cations varied among substrata. In rat GEC, alpha 2 beta 1 and/or alpha 3 beta 1 integrins appear to mediate adhesion to collagen I, collagen IV, and laminin. The alpha 3 beta 1 integrin is also the likely receptor for fibronectin, interacting through an RGD binding site. Furthermore, single integrins or combinations of integrins appear to have distinct ligand-binding functions that are differentially regulated by divalent cations. Characterization of GEC adhesion molecules may facilitate the understanding of mechanisms of glomerular development, and cell detachment or proliferation in immune glomerular injury."} {"id": "PMID:1280702", "title": "Arginase is a major pathway of L-arginine metabolism in nephritic glomeruli.", "content": "L-arginine can be metabolized to nitric oxide (NO) by nitric oxide synthase (NOS) and to urea and L-ornithine by arginase. Competition between these pathways for L-arginine in inflammatory sites has been suggested. In experimental glomerulonephritis glomeruli produce nitrite; a major source is macrophages. We hypothesized that arginase is present in glomeruli and may compete for substrate with NOS in glomerulonephritis. Therefore we examined both pathways in isolated nephritic glomeruli and peritoneal macrophages. Arginase activity was present in glomeruli, increased by > 500% in nephritic glomeruli compared to controls, and was predominant over NOS. Activity increased with L-NMMA (a NOS inhibitor), but this trend did not reach statistical significance. In macrophages both pathways were present; NOS predominated basally but this was reversed by L-NMMA. In contrast with glomeruli macrophage arginase activity increased after LPS stimulation. Levels of macrophage arginase activity could not account for activity in nephritic glomeruli, suggesting another source of arginase. This is the first demonstration of high arginase activity of nephritic glomeruli. Competition between arginase and NOS pathways suggests a regulatory mechanism of L-arginine metabolism within the glomerulus, with implications for the pathogenesis of injury and scarring in glomerulonephritis.", "contents": "Arginase is a major pathway of L-arginine metabolism in nephritic glomeruli. L-arginine can be metabolized to nitric oxide (NO) by nitric oxide synthase (NOS) and to urea and L-ornithine by arginase. Competition between these pathways for L-arginine in inflammatory sites has been suggested. In experimental glomerulonephritis glomeruli produce nitrite; a major source is macrophages. We hypothesized that arginase is present in glomeruli and may compete for substrate with NOS in glomerulonephritis. Therefore we examined both pathways in isolated nephritic glomeruli and peritoneal macrophages. Arginase activity was present in glomeruli, increased by > 500% in nephritic glomeruli compared to controls, and was predominant over NOS. Activity increased with L-NMMA (a NOS inhibitor), but this trend did not reach statistical significance. In macrophages both pathways were present; NOS predominated basally but this was reversed by L-NMMA. In contrast with glomeruli macrophage arginase activity increased after LPS stimulation. Levels of macrophage arginase activity could not account for activity in nephritic glomeruli, suggesting another source of arginase. This is the first demonstration of high arginase activity of nephritic glomeruli. Competition between arginase and NOS pathways suggests a regulatory mechanism of L-arginine metabolism within the glomerulus, with implications for the pathogenesis of injury and scarring in glomerulonephritis."} {"id": "PMID:1280703", "title": "Development and characterization of rabbit proximal tubular epithelial cell lines.", "content": "We have isolated rabbit kidney proximal tubular epithelial cell lines. The selection was based on their ability to form confluent monolayers on porous supports and to maintain receptor-mediated signal transduction and ion transport, characteristic of the proximal tubule. The isolation method consisted of several steps: (1) superficial cortical proximal tubule segments were microdissected and cultured on a matrix-coated porous support until cells formed a confluent monolayer; (2) primary cultures showing hormone-regulated ion transport typical for the proximal tubule were selected and co-cultured with irradiated fibroblasts; and (3) the epithelial cells surviving after several passages were expanded and passaged on porous substrates. Most of the cell lines developed in this manner were obtained by co-culture with irradiated fibroblasts producing a recombinant retrovirus encoding SV40 large T antigen and G418 resistance. However, SV40 T antigen expression was not essential for immortalization, since neither T antigen nor G418 resistance was detected in the isolated cell lines and co-culture with non-producing 3T3 cells gave similar results. One cell line (vEPT) has been characterized in some detail with respect to morphological, biochemical, and ion transport properties. This line forms confluent monolayers with apical microvilli, tight junctions, and convolutions of the basolateral plasma membrane. Once confluent, monolayers maintain conductances of 25 to 32 mS/cm2 for several weeks in culture and possess phlorizin-sensitive short-circuit current (Isc) in glucose containing media, indicative of apical Na(+)-glucose co-transport. vEPT cells also retain receptor and signaling mechanisms for angiotensin II (Ang II). Apical and basal Ang II and 5,6-epoxy-eicosatrienoic acid (5,6-EET) modulate the Isc in a manner similar to primary cultures. The cell lines share with primary cultures expression of the cytokeratins K8, K10/K11, and K19 (\"nomenclature\" [21]). They also retain several receptor and signal transduction mechanisms. For example, Ang II, arachidonate, bradykinin, 5,6-EET, parathyroid hormone (residues 1 through 34), and purine nucleotides increase cytosolic Ca2+, PTH elevates cAMP levels, and Ang II enhances proximal tubule-specific arachidonic acid metabolism.", "contents": "Development and characterization of rabbit proximal tubular epithelial cell lines. We have isolated rabbit kidney proximal tubular epithelial cell lines. The selection was based on their ability to form confluent monolayers on porous supports and to maintain receptor-mediated signal transduction and ion transport, characteristic of the proximal tubule. The isolation method consisted of several steps: (1) superficial cortical proximal tubule segments were microdissected and cultured on a matrix-coated porous support until cells formed a confluent monolayer; (2) primary cultures showing hormone-regulated ion transport typical for the proximal tubule were selected and co-cultured with irradiated fibroblasts; and (3) the epithelial cells surviving after several passages were expanded and passaged on porous substrates. Most of the cell lines developed in this manner were obtained by co-culture with irradiated fibroblasts producing a recombinant retrovirus encoding SV40 large T antigen and G418 resistance. However, SV40 T antigen expression was not essential for immortalization, since neither T antigen nor G418 resistance was detected in the isolated cell lines and co-culture with non-producing 3T3 cells gave similar results. One cell line (vEPT) has been characterized in some detail with respect to morphological, biochemical, and ion transport properties. This line forms confluent monolayers with apical microvilli, tight junctions, and convolutions of the basolateral plasma membrane. Once confluent, monolayers maintain conductances of 25 to 32 mS/cm2 for several weeks in culture and possess phlorizin-sensitive short-circuit current (Isc) in glucose containing media, indicative of apical Na(+)-glucose co-transport. vEPT cells also retain receptor and signaling mechanisms for angiotensin II (Ang II). Apical and basal Ang II and 5,6-epoxy-eicosatrienoic acid (5,6-EET) modulate the Isc in a manner similar to primary cultures. The cell lines share with primary cultures expression of the cytokeratins K8, K10/K11, and K19 (\"nomenclature\" [21]). They also retain several receptor and signal transduction mechanisms. For example, Ang II, arachidonate, bradykinin, 5,6-EET, parathyroid hormone (residues 1 through 34), and purine nucleotides increase cytosolic Ca2+, PTH elevates cAMP levels, and Ang II enhances proximal tubule-specific arachidonic acid metabolism."} {"id": "PMID:1280704", "title": "Tetrandrine inhibits both T and L calcium channel currents in ventricular cells.", "content": "Tetrandrine, a putative Ca2+ channel blocker, is extracted from the Chinese medicinal herb, Radix stephania tetrandrae. In the present study, the whole-cell version of the patch clamp technique was used to investigate the effects of tetrandrine on both T and L calcium channel currents in primary cultured neonatal rat ventricular cells. We show that tetrandrine inhibits both T and L calcium channel currents in ventricular cells. This inhibition of inward Ca2+ currents is concentration dependent and reversible. Tetrandrine does not shift the I-V relationship of the calcium currents. These results clearly demonstrate that tetrandrine acts as a calcium channel antagonist in ventricular cells. Previous data show that tetrandrine may be regarded as a wide-spectrum calcium channel antagonist.", "contents": "Tetrandrine inhibits both T and L calcium channel currents in ventricular cells. Tetrandrine, a putative Ca2+ channel blocker, is extracted from the Chinese medicinal herb, Radix stephania tetrandrae. In the present study, the whole-cell version of the patch clamp technique was used to investigate the effects of tetrandrine on both T and L calcium channel currents in primary cultured neonatal rat ventricular cells. We show that tetrandrine inhibits both T and L calcium channel currents in ventricular cells. This inhibition of inward Ca2+ currents is concentration dependent and reversible. Tetrandrine does not shift the I-V relationship of the calcium currents. These results clearly demonstrate that tetrandrine acts as a calcium channel antagonist in ventricular cells. Previous data show that tetrandrine may be regarded as a wide-spectrum calcium channel antagonist."} {"id": "PMID:1280705", "title": "Renal effects of alacepril in essential hypertension.", "content": "Short-term effects of alacepril, an angiotensin-converting enzyme inhibitor (ACEI), on renal function and hemodynamics were investigated in 10 hypertensive subjects (aged 55.7 +/- 9.5 years, mean +/- SD). Renal plasma flow (RPF) and glomerular filtration rate (GFR) were examined before and after 12-week administration of alacepril, by [131I]hippuran and [99mTc]DTPA, respectively. Alacepril (50 mg/day) caused a significant decrease in both systolic and diastolic blood pressure (SBP and DBP, from 161 +/- 8 to 140 +/- 10 mm Hg and from 100 +/- 3 to 90 +/- 5 mm Hg, respectively). Alacepril increased GFR (from 63.4 +/- 22.2 to 69.1 +/- 22.1 ml/min/1.73 m2, p less than 0.05) without changing RPF (from 438 +/- 194 to 432 +/- 148 ml/min/1.73 m2, p greater than 0.05). Serum creatinine and electrolytes were not changed by alacepril administration. These data show that short-term alacepril administration improves renal function, probably owing to relaxation of renal vasoconstriction.", "contents": "Renal effects of alacepril in essential hypertension. Short-term effects of alacepril, an angiotensin-converting enzyme inhibitor (ACEI), on renal function and hemodynamics were investigated in 10 hypertensive subjects (aged 55.7 +/- 9.5 years, mean +/- SD). Renal plasma flow (RPF) and glomerular filtration rate (GFR) were examined before and after 12-week administration of alacepril, by [131I]hippuran and [99mTc]DTPA, respectively. Alacepril (50 mg/day) caused a significant decrease in both systolic and diastolic blood pressure (SBP and DBP, from 161 +/- 8 to 140 +/- 10 mm Hg and from 100 +/- 3 to 90 +/- 5 mm Hg, respectively). Alacepril increased GFR (from 63.4 +/- 22.2 to 69.1 +/- 22.1 ml/min/1.73 m2, p less than 0.05) without changing RPF (from 438 +/- 194 to 432 +/- 148 ml/min/1.73 m2, p greater than 0.05). Serum creatinine and electrolytes were not changed by alacepril administration. These data show that short-term alacepril administration improves renal function, probably owing to relaxation of renal vasoconstriction."} {"id": "PMID:1280706", "title": "Hemodynamic and renal effects of the protein kinase inhibitor staurosporine in conscious rats.", "content": "To evaluate the pattern of hemodynamic responses produced by an inhibitor of protein kinase C (PKC), staurosporine 0.03-0.55 mg/kg was administered intravenously (i.v.) to conscious, normotensive rats chronically instrumented with vascular catheters for direct measurement of blood pressure (BP) and i.v. administration of drugs and either an aortic flow probe for measurement of cardiac output (CO) or miniaturized pulsed Doppler flow probes for measurement of hindquarter, renal, and mesenteric vascular resistances. Staurosporine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR) and increased heart rate (HR) in a dose-dependent manner. Because staurosporine decreased resistance in all three vascular beds monitored (hindquarter, renal, and mesenteric), staurosporine is probably a nonselective vasodilator that decreases MAP by decreasing resistance in a number of peripheral vascular beds. Staurosporine produced biphasic effects on CO, dF/dtmax and peak aortic blood flow; these parameters were significantly increased at doses less than 0.3 mg/kg and decreased to levels equal to or significantly less than control values at doses greater than 0.3 mg/kg. In comparison, the calcium channel blocker nitrendipine decreased MAP and TPR and increased HR, CO, dF/dtmax, and peak aortic flow in a dose-dependent manner over the entire dose range (0.01-1 mg/kg i.v.). Staurosporine (0.3 mg/kg) and nitrendipine (1 mg/kg) produced similar changes in MAP (-44 +/- 3 and -33 +/- 2 mm Hg, respectively), yet staurosporine affected dF/dtmax to a lesser extent than nitrendipine (-5 +/- 36 and 390 +/- 46 ml/s/s, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Hemodynamic and renal effects of the protein kinase inhibitor staurosporine in conscious rats. To evaluate the pattern of hemodynamic responses produced by an inhibitor of protein kinase C (PKC), staurosporine 0.03-0.55 mg/kg was administered intravenously (i.v.) to conscious, normotensive rats chronically instrumented with vascular catheters for direct measurement of blood pressure (BP) and i.v. administration of drugs and either an aortic flow probe for measurement of cardiac output (CO) or miniaturized pulsed Doppler flow probes for measurement of hindquarter, renal, and mesenteric vascular resistances. Staurosporine decreased mean arterial pressure (MAP) and total peripheral resistance (TPR) and increased heart rate (HR) in a dose-dependent manner. Because staurosporine decreased resistance in all three vascular beds monitored (hindquarter, renal, and mesenteric), staurosporine is probably a nonselective vasodilator that decreases MAP by decreasing resistance in a number of peripheral vascular beds. Staurosporine produced biphasic effects on CO, dF/dtmax and peak aortic blood flow; these parameters were significantly increased at doses less than 0.3 mg/kg and decreased to levels equal to or significantly less than control values at doses greater than 0.3 mg/kg. In comparison, the calcium channel blocker nitrendipine decreased MAP and TPR and increased HR, CO, dF/dtmax, and peak aortic flow in a dose-dependent manner over the entire dose range (0.01-1 mg/kg i.v.). Staurosporine (0.3 mg/kg) and nitrendipine (1 mg/kg) produced similar changes in MAP (-44 +/- 3 and -33 +/- 2 mm Hg, respectively), yet staurosporine affected dF/dtmax to a lesser extent than nitrendipine (-5 +/- 36 and 390 +/- 46 ml/s/s, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280707", "title": "Progesterone potentiation of bupivacaine arrhythmogenicity in pentobarbital-anesthetized rats and beating rat heart cell cultures.", "content": "The effects of progesterone treatment on bupivacaine arrhythmogenicity in beating rat heart myocyte cultures and on anesthetized rats were determined. After determining the bupivacaine AD50 (the concentration of bupivacaine that caused 50% of all beating rat heart myocyte cultures to become arrhythmic), we determined the effect of 1-hour progesterone HCl exposure on myocyte contractile rhythm. Each concentration of progesterone (6.25, 12.5, 25, and 50 micrograms/ml) caused a significant and concentration-dependent reduction in the AD50 for bupivacaine. Estradiol treatment also increased the arrhythmogenicity of bupivacaine in myocyte cultures, but was only one fourth as potent as progesterone. Neither progesterone nor estradiol effects on bupivacaine arrhythmogenicity were potentiated by epinephrine. Chronic progesterone pretreatment (5 mg/kg/day for 21 days) caused a significant increase in bupivacaine arrhythmogenicity in intact pentobarbital-anesthetized rats. There was a significant decrease in the time to onset of arrhythmia as compared with control nonprogesterone-treated rats (6.2 +/- 1.3 vs. 30.8 +/- 2.5 min, mean +/- SE). The results of this study indicate that progesterone can potentiate bupivacaine arrhythmogenicity both in vivo and in vitro. Potentiation of bupivacaine arrhythmia in myocyte cultures suggests that this effect is at least partly mediated at the myocyte level.", "contents": "Progesterone potentiation of bupivacaine arrhythmogenicity in pentobarbital-anesthetized rats and beating rat heart cell cultures. The effects of progesterone treatment on bupivacaine arrhythmogenicity in beating rat heart myocyte cultures and on anesthetized rats were determined. After determining the bupivacaine AD50 (the concentration of bupivacaine that caused 50% of all beating rat heart myocyte cultures to become arrhythmic), we determined the effect of 1-hour progesterone HCl exposure on myocyte contractile rhythm. Each concentration of progesterone (6.25, 12.5, 25, and 50 micrograms/ml) caused a significant and concentration-dependent reduction in the AD50 for bupivacaine. Estradiol treatment also increased the arrhythmogenicity of bupivacaine in myocyte cultures, but was only one fourth as potent as progesterone. Neither progesterone nor estradiol effects on bupivacaine arrhythmogenicity were potentiated by epinephrine. Chronic progesterone pretreatment (5 mg/kg/day for 21 days) caused a significant increase in bupivacaine arrhythmogenicity in intact pentobarbital-anesthetized rats. There was a significant decrease in the time to onset of arrhythmia as compared with control nonprogesterone-treated rats (6.2 +/- 1.3 vs. 30.8 +/- 2.5 min, mean +/- SE). The results of this study indicate that progesterone can potentiate bupivacaine arrhythmogenicity both in vivo and in vitro. Potentiation of bupivacaine arrhythmia in myocyte cultures suggests that this effect is at least partly mediated at the myocyte level."} {"id": "PMID:1280708", "title": "Effects of a combination of acidosis, lactate, and lysophosphatidylcholine on action potentials and ionic currents in guinea pig ventricular myocytes.", "content": "The aim of this study was to determine the electrophysiological effects of a combination of factors that are of importance during myocardial ischaemia, i.e., acidosis, lactate, and lysophosphatidylcholine, in ventricular myocytes. Intracellular microelectrode techniques were used to record action potential and ionic currents in ventricular myocytes before, during, and after a 30 min exposure to a salt solution that was acidotic (pH 6.8), and contained lactate (10 mM) and lysophosphatidylcholine (5 microM). Single ventricular myocytes were dissociated enzymatically from guinea pig hearts, and perfused with either normal or modified physiological salt solution. Combined acidosis, lactate, and lysophosphatidylcholine resulted in a reduction in the resting membrane potential and maximum rate of depolarisation of phase 0, and flattening of the plateau but prolongation of the action potential duration at 90% repolarisation. Automatic activity was also induced in about one-third of the cells studied. Under voltage-clamp conditions, this combination of factors reduced the peak inward calcium current, on repolarisation after a depolarising step, reduced the steady-state outward current, and reduced the delayed rectifier current, measured as the tail current at the end of a depolarising clamp step. In some cells, a transient inward current was induced by the modified salt solution. It is concluded that the characteristic alterations in action potential characteristics induced by a combination of acidosis, lactate, and lysophosphatidylcholine are likely to result from reductions in the inward Ca current and the background and delayed rectifier K current.", "contents": "Effects of a combination of acidosis, lactate, and lysophosphatidylcholine on action potentials and ionic currents in guinea pig ventricular myocytes. The aim of this study was to determine the electrophysiological effects of a combination of factors that are of importance during myocardial ischaemia, i.e., acidosis, lactate, and lysophosphatidylcholine, in ventricular myocytes. Intracellular microelectrode techniques were used to record action potential and ionic currents in ventricular myocytes before, during, and after a 30 min exposure to a salt solution that was acidotic (pH 6.8), and contained lactate (10 mM) and lysophosphatidylcholine (5 microM). Single ventricular myocytes were dissociated enzymatically from guinea pig hearts, and perfused with either normal or modified physiological salt solution. Combined acidosis, lactate, and lysophosphatidylcholine resulted in a reduction in the resting membrane potential and maximum rate of depolarisation of phase 0, and flattening of the plateau but prolongation of the action potential duration at 90% repolarisation. Automatic activity was also induced in about one-third of the cells studied. Under voltage-clamp conditions, this combination of factors reduced the peak inward calcium current, on repolarisation after a depolarising step, reduced the steady-state outward current, and reduced the delayed rectifier current, measured as the tail current at the end of a depolarising clamp step. In some cells, a transient inward current was induced by the modified salt solution. It is concluded that the characteristic alterations in action potential characteristics induced by a combination of acidosis, lactate, and lysophosphatidylcholine are likely to result from reductions in the inward Ca current and the background and delayed rectifier K current."} {"id": "PMID:1280709", "title": "Prostaglandin E2 in dogs with heart failure: hemodynamic, hormonal, and renal effects.", "content": "To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the hemodynamic, hormonal, and renal effects of prostaglandin E2 (1.5-150 ng/kg/min) in six conscious dogs before and after induction of heart failure by right ventricular pacing (250 beats/min, 10 days). In healthy dogs, PGE2 decreased the mean arterial pressure (MAP) by a reduction in total peripheral resistance (TPR), increased cardiac output (CO), stroke volume (SV), and heart rate with no effect on right atrial pressure (RAP). Plasma levels of renin (PRC) and norepinephrine (NE) were increased at the highest dosage. Renal plasma flow (RPF) and sodium excretion (UNaV) were augmented without a change in the glomerular filtration rate (GFR) and urine flow (UF). In dogs with heart failure, PGE2 lowered the MAP and TPR and elevated the CO and SV without an effect on the RAP, PRC, and NE. The RPF and GFR were not changed, but the increase in UNaV was preserved and UF significantly augmented. In experimental heart failure, PGE2 increases the CO due to arteriolar dilation and afterload reduction without inducing further neurohumoral activation and exerts potent natriuretic and diuretic action. Therefore, PGE2 may have beneficial effects in heart failure therapy.", "contents": "Prostaglandin E2 in dogs with heart failure: hemodynamic, hormonal, and renal effects. To test the efficacy of exogenous prostaglandins for vasodilator therapy in heart failure, we studied the hemodynamic, hormonal, and renal effects of prostaglandin E2 (1.5-150 ng/kg/min) in six conscious dogs before and after induction of heart failure by right ventricular pacing (250 beats/min, 10 days). In healthy dogs, PGE2 decreased the mean arterial pressure (MAP) by a reduction in total peripheral resistance (TPR), increased cardiac output (CO), stroke volume (SV), and heart rate with no effect on right atrial pressure (RAP). Plasma levels of renin (PRC) and norepinephrine (NE) were increased at the highest dosage. Renal plasma flow (RPF) and sodium excretion (UNaV) were augmented without a change in the glomerular filtration rate (GFR) and urine flow (UF). In dogs with heart failure, PGE2 lowered the MAP and TPR and elevated the CO and SV without an effect on the RAP, PRC, and NE. The RPF and GFR were not changed, but the increase in UNaV was preserved and UF significantly augmented. In experimental heart failure, PGE2 increases the CO due to arteriolar dilation and afterload reduction without inducing further neurohumoral activation and exerts potent natriuretic and diuretic action. Therefore, PGE2 may have beneficial effects in heart failure therapy."} {"id": "PMID:1280710", "title": "Differential effects of alpha 1- and alpha 2-adrenoceptor agonists on peripheral vasoconstriction in pithed diabetic rats.", "content": "The pressor responses to selective alpha 1-adrenoceptor agonists (cirazoline and methoxamine) and to alpha 2-adrenoceptor agonists (UK-14,304 and B-HT 933) were investigated in pithed, streptozotocin-induced diabetic rats and age-matched control animals. Three months after induction of diabetes, the basal values of diastolic blood pressure (DBP) were the same in pithed diabetic and control rats (34.3 +/- 4.4 vs. 32.8 +/- 4.4 mm Hg, p greater than 0.05, n = 30). In pithed diabetic rats, dose-response curves for the vasoconstrictor effects of cirazoline and methoxamine were shifted to the right with a slight decrease in the maximum response as compared with those in control animals. In contrast, no shift in dose-response curves for the alpha 2-adrenoceptor-mediated vasoconstrictor effects was observed, as reflected by similar pD2 values. A pronounced decrease in the maximum pressor response to the alpha 2-adrenoceptor agonists could be demonstrated. This reduction was significantly greater than that of the alpha 1-adrenoceptor agonists. In conclusion, the functional role of alpha 1- and alpha 2-adrenoceptors in the peripheral resistance vessels appears to be differentially influenced by the diabetic state.", "contents": "Differential effects of alpha 1- and alpha 2-adrenoceptor agonists on peripheral vasoconstriction in pithed diabetic rats. The pressor responses to selective alpha 1-adrenoceptor agonists (cirazoline and methoxamine) and to alpha 2-adrenoceptor agonists (UK-14,304 and B-HT 933) were investigated in pithed, streptozotocin-induced diabetic rats and age-matched control animals. Three months after induction of diabetes, the basal values of diastolic blood pressure (DBP) were the same in pithed diabetic and control rats (34.3 +/- 4.4 vs. 32.8 +/- 4.4 mm Hg, p greater than 0.05, n = 30). In pithed diabetic rats, dose-response curves for the vasoconstrictor effects of cirazoline and methoxamine were shifted to the right with a slight decrease in the maximum response as compared with those in control animals. In contrast, no shift in dose-response curves for the alpha 2-adrenoceptor-mediated vasoconstrictor effects was observed, as reflected by similar pD2 values. A pronounced decrease in the maximum pressor response to the alpha 2-adrenoceptor agonists could be demonstrated. This reduction was significantly greater than that of the alpha 1-adrenoceptor agonists. In conclusion, the functional role of alpha 1- and alpha 2-adrenoceptors in the peripheral resistance vessels appears to be differentially influenced by the diabetic state."} {"id": "PMID:1280711", "title": "Enhanced inotropic responsiveness to alpha 1-adrenoceptor stimulation in isolated working hearts from diabetic rats.", "content": "We compared the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline and the calcium entry promoter Bay K 8644 in isolated working hearts from streptozotocin (STZ) diabetic rats and age-matched controls. The maximal rate of contraction and cardiac output (CO) were unaffected by diabetes. The maximal rate of relaxation was significantly decreased in diabetic hearts as compared with controls. Cirazoline (10(-9)-10(-6) M) induced an increase in both maximal rate of contraction and relaxation in diabetic and control hearts. Notably, the maximal rate of contraction was significantly greater in diabetic hearts. Changes in maximal rate of relaxation were similar in both preparations. A significant increase in CO was observed in diabetic hearts, but not in controls. With Bay K 8644 (10(-9)-10(-6) M) added, the increase in maximal rate of contraction and relaxation as well as CO were not significantly different in the two preparations although the changes in maximal rate of relaxation tended to be decreased in diabetic hearts. Our results indicate that cardiac alpha 1-adrenoceptors appear to gain greater functional importance in regulation of myocardial inotropism in diabetes mellitus.", "contents": "Enhanced inotropic responsiveness to alpha 1-adrenoceptor stimulation in isolated working hearts from diabetic rats. We compared the inotropic responsiveness to the alpha 1-adrenoceptor agonist cirazoline and the calcium entry promoter Bay K 8644 in isolated working hearts from streptozotocin (STZ) diabetic rats and age-matched controls. The maximal rate of contraction and cardiac output (CO) were unaffected by diabetes. The maximal rate of relaxation was significantly decreased in diabetic hearts as compared with controls. Cirazoline (10(-9)-10(-6) M) induced an increase in both maximal rate of contraction and relaxation in diabetic and control hearts. Notably, the maximal rate of contraction was significantly greater in diabetic hearts. Changes in maximal rate of relaxation were similar in both preparations. A significant increase in CO was observed in diabetic hearts, but not in controls. With Bay K 8644 (10(-9)-10(-6) M) added, the increase in maximal rate of contraction and relaxation as well as CO were not significantly different in the two preparations although the changes in maximal rate of relaxation tended to be decreased in diabetic hearts. Our results indicate that cardiac alpha 1-adrenoceptors appear to gain greater functional importance in regulation of myocardial inotropism in diabetes mellitus."} {"id": "PMID:1280712", "title": "Bay K 8644 is a negative inotrope in the presence of arachidonic acid but not eicosapentaenoic acid.", "content": "The inotropic and radioligand binding characteristics of arachidonic acid (AA) and the fish oil derivative, eicosapentaenoic acid (EPA), were studied. AA alone was a concentration-dependent negative inotrope in isolated hamster papillary muscles. The negative inotropic effect of AA was enhanced 500-fold by the coadministration of indomethacin (cyclo-oxygenase inhibitor) and caffeic acid (lipoxygenase inhibitor). The dihydropyridine calcium channel agonist Bay K 8644 (BK) was a concentration-dependent positive inotrope. BK in the presence of AA was a concentration-dependent negative inotrope. The negative inotropic effect of BK in the presence of AA was blocked by caffeic acid but not indomethacin. EPA alone was a concentration-dependent negative inotrope. EPA had no effect on the positive inotropic effect of BK. Scatchard analyses of [3H]nitrendipine (dihydropyridine) binding to cardiac membranes in the presence of AA or EPA resulted in a decrease in the KD (-1/slope) with no effect on Bmax (x intercept). Kinetic studies further revealed that both AA and EPA enhanced the off rate of [3H]nitrendipine binding. These data suggest that both AA and EPA mediate similar direct negative inotropic effects through cardiac sarcolemmal calcium channels. A unique effect on E-C coupling by AA, not shared by EPA, is mediated through the lipoxygenase pathway (leukotrienes). AA and its eicosanoid products may play critically important roles in regulating myocardial contractility during acute and chronic myocardial ischemia. Differences between AA and EPA may contribute to the beneficial effects of dietary fish oils enriched in EPA.", "contents": "Bay K 8644 is a negative inotrope in the presence of arachidonic acid but not eicosapentaenoic acid. The inotropic and radioligand binding characteristics of arachidonic acid (AA) and the fish oil derivative, eicosapentaenoic acid (EPA), were studied. AA alone was a concentration-dependent negative inotrope in isolated hamster papillary muscles. The negative inotropic effect of AA was enhanced 500-fold by the coadministration of indomethacin (cyclo-oxygenase inhibitor) and caffeic acid (lipoxygenase inhibitor). The dihydropyridine calcium channel agonist Bay K 8644 (BK) was a concentration-dependent positive inotrope. BK in the presence of AA was a concentration-dependent negative inotrope. The negative inotropic effect of BK in the presence of AA was blocked by caffeic acid but not indomethacin. EPA alone was a concentration-dependent negative inotrope. EPA had no effect on the positive inotropic effect of BK. Scatchard analyses of [3H]nitrendipine (dihydropyridine) binding to cardiac membranes in the presence of AA or EPA resulted in a decrease in the KD (-1/slope) with no effect on Bmax (x intercept). Kinetic studies further revealed that both AA and EPA enhanced the off rate of [3H]nitrendipine binding. These data suggest that both AA and EPA mediate similar direct negative inotropic effects through cardiac sarcolemmal calcium channels. A unique effect on E-C coupling by AA, not shared by EPA, is mediated through the lipoxygenase pathway (leukotrienes). AA and its eicosanoid products may play critically important roles in regulating myocardial contractility during acute and chronic myocardial ischemia. Differences between AA and EPA may contribute to the beneficial effects of dietary fish oils enriched in EPA."} {"id": "PMID:1280713", "title": "Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans.", "content": "Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Hemodynamic and neurohumoral responses to intravenous nicorandil in congestive heart failure in humans. Nicorandil is a vasodilator drug that combines potassium channel opening properties with nitrate effects. The resulting potent and unique vasodilating properties suggest a potential therapeutic role in congestive heart failure. We therefore studied the acute hemodynamic and neurohumoral responses to nicorandil, given as single intravenous bolus doses of 158, 251, 398, or 630 micrograms/kg, to 22 patients with chronic congestive heart failure (ejection fraction less than 40%). Hemodynamic responses occurred within 5 min of dosing and terminated within 240 min. The heart rate was significantly increased only at 5 min after the 158 micrograms/kg dose, and was unchanged after all other doses. The mean arterial pressure was reduced only by the 398 and 630 micrograms/kg doses. The pulmonary capillary wedge pressure and right atrial pressure were significantly reduced by all doses within the initial 30 min; this reduction in pulmonary capillary wedge pressure was better sustained over time by the two larger doses, whereas the reduction in right atrial pressure was sustained only by the 158 micrograms/kg dose. The cardiac index was reduced by the 158 micrograms/kg dose, but increased after 251, 398, and 630 micrograms/kg of nicorandil. Plasma nicorandil concentrations were positively correlated with changes in cardiac index, systemic arterial pressure, pulmonary capillary wedge pressure, heart rate, and systemic vascular resistance. When measured 1 h after dosing, plasma immunoreactive ANF decreased, norepinephrine concentrations did not change, and plasma renin activity increased, but only at the 630 micrograms/kg dose level.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280714", "title": "Cardiovascular pharmacology of the vasodilator-cardiotonic agent, 349U85.", "content": "349U85 is a chemically novel, nonglycoside, noncatecholamine cardiotonic-vasodilator agent with a unique cardiovascular profile in vitro and in vivo. 349U85 and milrinone, 10(-6) to 3 x 10(-5) M each, produce concentration-dependent increases in tension development of 33-60% and 37-60%, respectively, with corresponding 5-18% and 17-55% increases in contractile rate, respectively, in guinea pig spontaneously beating isolated paired atria. In anesthetized dogs, 349U85 at 0.03-1.0 mg/kg i.v. produces dose-dependent increases in left ventricular contractility (dP/dt) of 12-159%, decreases in total peripheral resistance of 11-38%, and increases in heart rate of 3-26%. Milrinone, Cl-914, and enoximone produce comparable increases in dP/dt and decreases in peripheral resistance yet increase the heart rate a maximum of 71, 49, and 41%, respectively. Intra-arterial injection of 349U85 into the vascularly isolated hindlimb of anesthetized dogs produces dose-dependent direct vasodilation. The inotropic effect of 349U85, following a single intravenous dose, is sustained in excess of 4 h while comparable initial inotropic effects of milrinone and enoximone are sustained less than 1 and 2.5 h, respectively. 349U85 effectively reverses acute cardiac depression in anesthetized dogs with a duration exceeding that of milrinone. In conscious dogs, 349U85, at 0.1-1.0 mg/kg p.o., produces a dose-dependent positive inotropic effect (15-73%) with no significant effect on heart rate. Following a single oral dose of 349U85, the inotropic effect is sustained in excess of 6 h. Results of these studies indicate that 349U85 is a potent, long-lasting positive inotropic and vasodilator agent with minimal heart rate effect in vitro and in vivo and is different from a number of reference inodilators.", "contents": "Cardiovascular pharmacology of the vasodilator-cardiotonic agent, 349U85. 349U85 is a chemically novel, nonglycoside, noncatecholamine cardiotonic-vasodilator agent with a unique cardiovascular profile in vitro and in vivo. 349U85 and milrinone, 10(-6) to 3 x 10(-5) M each, produce concentration-dependent increases in tension development of 33-60% and 37-60%, respectively, with corresponding 5-18% and 17-55% increases in contractile rate, respectively, in guinea pig spontaneously beating isolated paired atria. In anesthetized dogs, 349U85 at 0.03-1.0 mg/kg i.v. produces dose-dependent increases in left ventricular contractility (dP/dt) of 12-159%, decreases in total peripheral resistance of 11-38%, and increases in heart rate of 3-26%. Milrinone, Cl-914, and enoximone produce comparable increases in dP/dt and decreases in peripheral resistance yet increase the heart rate a maximum of 71, 49, and 41%, respectively. Intra-arterial injection of 349U85 into the vascularly isolated hindlimb of anesthetized dogs produces dose-dependent direct vasodilation. The inotropic effect of 349U85, following a single intravenous dose, is sustained in excess of 4 h while comparable initial inotropic effects of milrinone and enoximone are sustained less than 1 and 2.5 h, respectively. 349U85 effectively reverses acute cardiac depression in anesthetized dogs with a duration exceeding that of milrinone. In conscious dogs, 349U85, at 0.1-1.0 mg/kg p.o., produces a dose-dependent positive inotropic effect (15-73%) with no significant effect on heart rate. Following a single oral dose of 349U85, the inotropic effect is sustained in excess of 6 h. Results of these studies indicate that 349U85 is a potent, long-lasting positive inotropic and vasodilator agent with minimal heart rate effect in vitro and in vivo and is different from a number of reference inodilators."} {"id": "PMID:1280715", "title": "Comparison of negative inotropic and vasodilator effects of isradipine and nifedipine after complete autonomic blockade in ischemic heart disease.", "content": "The cardiodepressant and vasodilator effects of an intravenous (i.v.) infusion of 0.5 mg isradipine or 2 mg nifedipine were interindividually (10 vs. 10 patients) compared in a double-blind study in patients with stable coronary heart disease. To minimize vasodilation-induced autonomic reflex mechanisms, which may counterbalance negative inotropic effects after acute administration of calcium antagonists, i.v. autonomic blockade was produced by 0.2 mg/kg propranolol and 0.04 mg/kg atropine. Systemic hemodynamics were measured before and 15 min after the end of the 15-min calcium antagonist infusion. After administration of both drugs, heart rate (HR) decreased similarly during the observation period (isradipine from 93 +/- 10 to 88 +/- 9 beats/min and nifedipine from 84 +/- 9 to 79 +/- 6 beats/min, both p less than or equal to 0.01). The reduction in total peripheral resistance (TPR) was significantly (p less than or equal to 0.01) greater after isradipine (from 1,376 +/- 285 to 1,002 +/- 224 dynes s cm-5) than after nifedipine (1,258 +/- 262 to 1,112 +/- 225 dynes s cm-5). Between the two drugs, the difference in the reduction of afterload independent dP/dt40, determined by tip-manometry, reached borderline significance (p = 0.08) (isradipine from 1,197 +/- 258 to 1,157 +/- 225 mm Hg/s, NS and nifedipine 1,228 +/- 226 to 1,109 +/- 227 mm Hg/s, p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Comparison of negative inotropic and vasodilator effects of isradipine and nifedipine after complete autonomic blockade in ischemic heart disease. The cardiodepressant and vasodilator effects of an intravenous (i.v.) infusion of 0.5 mg isradipine or 2 mg nifedipine were interindividually (10 vs. 10 patients) compared in a double-blind study in patients with stable coronary heart disease. To minimize vasodilation-induced autonomic reflex mechanisms, which may counterbalance negative inotropic effects after acute administration of calcium antagonists, i.v. autonomic blockade was produced by 0.2 mg/kg propranolol and 0.04 mg/kg atropine. Systemic hemodynamics were measured before and 15 min after the end of the 15-min calcium antagonist infusion. After administration of both drugs, heart rate (HR) decreased similarly during the observation period (isradipine from 93 +/- 10 to 88 +/- 9 beats/min and nifedipine from 84 +/- 9 to 79 +/- 6 beats/min, both p less than or equal to 0.01). The reduction in total peripheral resistance (TPR) was significantly (p less than or equal to 0.01) greater after isradipine (from 1,376 +/- 285 to 1,002 +/- 224 dynes s cm-5) than after nifedipine (1,258 +/- 262 to 1,112 +/- 225 dynes s cm-5). Between the two drugs, the difference in the reduction of afterload independent dP/dt40, determined by tip-manometry, reached borderline significance (p = 0.08) (isradipine from 1,197 +/- 258 to 1,157 +/- 225 mm Hg/s, NS and nifedipine 1,228 +/- 226 to 1,109 +/- 227 mm Hg/s, p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280716", "title": "Contrasting effects of cyclic AMP increase caused by beta-adrenergic stimulation or by adenylate cyclase activation on ventricular fibrillation threshold of isolated rat heart.", "content": "Increased myocardial tissue cyclic AMP has been associated with both a positive inotropic and a proarrhythmic effect. We wished to determine whether two agents that increase myocardial cyclic AMP levels by different mechanisms would induce comparable changes in vulnerability of the heart to ventricular fibrillation (VF) and in the inotropic status. Using an isolated perfused rat heart model, we studied the effects of beta-adrenoceptor stimulation by isoproterenol (ISO) and direct activation of adenylate cyclase by forskolin. The ventricular fibrillation threshold (VFT) was taken as an index of the vulnerability to VF and peak left ventricular systolic pressure (LVSP) as a measure of the force of LV contraction. ISO resulted in a dose-related increase in tissue cyclic AMP with a corresponding decrease in VFT and a marked increase in LVSP. Forskolin produced a delayed but exponential increase in cyclic AMP at concentrations greater than 3 x 10(-7) M with relatively small increases in LVSP. With forskolin, the VFT decreased only at extremely high cyclic AMP levels, suggesting that the drug had increased cyclic AMP in a compartmentalized manner. The discrepant effects of ISO and forskolin on VFT could not be explained by changes in heart rate (HR). These results show that an increase in tissue cyclic AMP can have markedly different arrhythmogenic effects depending on the mechanism by which cyclic AMP is increased.", "contents": "Contrasting effects of cyclic AMP increase caused by beta-adrenergic stimulation or by adenylate cyclase activation on ventricular fibrillation threshold of isolated rat heart. Increased myocardial tissue cyclic AMP has been associated with both a positive inotropic and a proarrhythmic effect. We wished to determine whether two agents that increase myocardial cyclic AMP levels by different mechanisms would induce comparable changes in vulnerability of the heart to ventricular fibrillation (VF) and in the inotropic status. Using an isolated perfused rat heart model, we studied the effects of beta-adrenoceptor stimulation by isoproterenol (ISO) and direct activation of adenylate cyclase by forskolin. The ventricular fibrillation threshold (VFT) was taken as an index of the vulnerability to VF and peak left ventricular systolic pressure (LVSP) as a measure of the force of LV contraction. ISO resulted in a dose-related increase in tissue cyclic AMP with a corresponding decrease in VFT and a marked increase in LVSP. Forskolin produced a delayed but exponential increase in cyclic AMP at concentrations greater than 3 x 10(-7) M with relatively small increases in LVSP. With forskolin, the VFT decreased only at extremely high cyclic AMP levels, suggesting that the drug had increased cyclic AMP in a compartmentalized manner. The discrepant effects of ISO and forskolin on VFT could not be explained by changes in heart rate (HR). These results show that an increase in tissue cyclic AMP can have markedly different arrhythmogenic effects depending on the mechanism by which cyclic AMP is increased."} {"id": "PMID:1280717", "title": "Protective effect of cicletanine on hypertension-induced decreases in the renal kallikrein-kinin and prostaglandin systems in stroke-prone spontaneously hypertensive rats.", "content": "We investigated the effect of two oral (p.o.) doses of cicletanine (5 and 30 mg/kg/day) for 4 weeks on urinary excretion (UKE), renal concentration (RKC) of kallikrein, and prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha urinary excretion of stroke-prone (SP) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) rats submitted to a high sodium intake (1%). Both doses of cicletanine induced a significant antihypertensive effect in treated SHR as compared with hypertensive untreated controls (HC). After 4-week treatment, a significant difference in mortality was observed between normotensive controls (NC) (0%) and HC (84%). Both doses of cicletanine reduced the mortality of hypertensive animals (8% SHR with 5 mg and 24% SHR with 30 mg vs. 84% in HC). Whereas UKE and RKC were decreased in HC during the progression of untreated hypertension from week 1 to week 4, both doses of cicletanine administration significantly prevented this decrease. Consistently with maintenance of UKE during the course of hypertension, the level of tissue kallikrein was higher in hypertensive cicletanine-treated than in untreated SHR. This increased RKC was associated with a significantly higher rate of kallikrein biosynthesis. The increased level of the urinary excretion and tissue concentration of PGE2 and 6-keto-PGF1 alpha in cicletanine-treated SHR as compared with untreated animals was also of interest. This protective effect on PG excretion correlated with that on kallikrein excretion. The results confirm the efficiency of cicletatine as an antihypertensive treatment. The antihypertensive action includes protective effects on potential vasodepressor kallikrein-kinin and prostaglandin systems.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Protective effect of cicletanine on hypertension-induced decreases in the renal kallikrein-kinin and prostaglandin systems in stroke-prone spontaneously hypertensive rats. We investigated the effect of two oral (p.o.) doses of cicletanine (5 and 30 mg/kg/day) for 4 weeks on urinary excretion (UKE), renal concentration (RKC) of kallikrein, and prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha urinary excretion of stroke-prone (SP) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) rats submitted to a high sodium intake (1%). Both doses of cicletanine induced a significant antihypertensive effect in treated SHR as compared with hypertensive untreated controls (HC). After 4-week treatment, a significant difference in mortality was observed between normotensive controls (NC) (0%) and HC (84%). Both doses of cicletanine reduced the mortality of hypertensive animals (8% SHR with 5 mg and 24% SHR with 30 mg vs. 84% in HC). Whereas UKE and RKC were decreased in HC during the progression of untreated hypertension from week 1 to week 4, both doses of cicletanine administration significantly prevented this decrease. Consistently with maintenance of UKE during the course of hypertension, the level of tissue kallikrein was higher in hypertensive cicletanine-treated than in untreated SHR. This increased RKC was associated with a significantly higher rate of kallikrein biosynthesis. The increased level of the urinary excretion and tissue concentration of PGE2 and 6-keto-PGF1 alpha in cicletanine-treated SHR as compared with untreated animals was also of interest. This protective effect on PG excretion correlated with that on kallikrein excretion. The results confirm the efficiency of cicletatine as an antihypertensive treatment. The antihypertensive action includes protective effects on potential vasodepressor kallikrein-kinin and prostaglandin systems.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280718", "title": "Effects of yohimbine on heart rate variability in panic disorder patients and normal controls: a study of power spectral analysis of heart rate.", "content": "We studied the effects of yohimbine on heart rate (HR) variability in 13 normal controls and 13 patients with panic disorder. Yohimbine produced a significant increase in SD of HR in standing posture in both patients (p = 0.01) and normal controls (p = 0.025). Panic disorder patients had a significant increase in standing absolute midfrequency (MF) power (0.07-0.15 Hz) after administration of yohimbine (p = 0.002). The ratio of post- to preyohimbine standing MF power (0.07-0.15 Hz) during standing was significantly higher in patients as compared with controls (2.3 +/- 1.08 vs. 1.33 +/- 0.38; p = 0.01), which suggests an increased responsivity of panic disorder patients to the adrenergic effects of yohimbine.", "contents": "Effects of yohimbine on heart rate variability in panic disorder patients and normal controls: a study of power spectral analysis of heart rate. We studied the effects of yohimbine on heart rate (HR) variability in 13 normal controls and 13 patients with panic disorder. Yohimbine produced a significant increase in SD of HR in standing posture in both patients (p = 0.01) and normal controls (p = 0.025). Panic disorder patients had a significant increase in standing absolute midfrequency (MF) power (0.07-0.15 Hz) after administration of yohimbine (p = 0.002). The ratio of post- to preyohimbine standing MF power (0.07-0.15 Hz) during standing was significantly higher in patients as compared with controls (2.3 +/- 1.08 vs. 1.33 +/- 0.38; p = 0.01), which suggests an increased responsivity of panic disorder patients to the adrenergic effects of yohimbine."} {"id": "PMID:1280719", "title": "Reduction of canine myocardial infarct size by CI-959, an inhibitor of inflammatory cell activation.", "content": "CI-959, a cell-activation inhibitor that prevents the formation of oxygen-derived free radicals by inflammatory cells, was studied to determine its effects on myocardial infarct size and subsequent scar formation in dogs. The left circumflex coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Drug infusion was started 15 min before reperfusion at a loading dose of 8 mg/kg i.v., followed immediately by 2 mg/kg i.v. infused over 80 min. The infarct size, assessed by TTC staining techniques, was significantly reduced in 12 dogs treated with CI-959 (23.3 +/- 3.6% of the area at risk) when compared to 11 vehicle-treated animals (35.5 +/- 4% of the area at risk, p less than 0.05). This reduction in infarct size was not attributed to changes in regional myocardial blood flow, as measured by radioactive microspheres, or to a reduction in myocardial oxygen demand, as estimated by changes in the rate-pressure product. The scar thickness, measured after a 6-week recovery period in 9 animals treated with CI-959, was not significantly reduced in comparison with 11 controls. In vitro, CI-959 effectively inhibited oxygen free radical formation by canine neutrophils. The results of this study show that CI-959 significantly reduces the myocardial infarct size without causing scar thinning, which might lead to ventricular aneurysm, and suggests the most likely mechanism for its beneficial action is the prevention of formation of toxic oxygen radicals.", "contents": "Reduction of canine myocardial infarct size by CI-959, an inhibitor of inflammatory cell activation. CI-959, a cell-activation inhibitor that prevents the formation of oxygen-derived free radicals by inflammatory cells, was studied to determine its effects on myocardial infarct size and subsequent scar formation in dogs. The left circumflex coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Drug infusion was started 15 min before reperfusion at a loading dose of 8 mg/kg i.v., followed immediately by 2 mg/kg i.v. infused over 80 min. The infarct size, assessed by TTC staining techniques, was significantly reduced in 12 dogs treated with CI-959 (23.3 +/- 3.6% of the area at risk) when compared to 11 vehicle-treated animals (35.5 +/- 4% of the area at risk, p less than 0.05). This reduction in infarct size was not attributed to changes in regional myocardial blood flow, as measured by radioactive microspheres, or to a reduction in myocardial oxygen demand, as estimated by changes in the rate-pressure product. The scar thickness, measured after a 6-week recovery period in 9 animals treated with CI-959, was not significantly reduced in comparison with 11 controls. In vitro, CI-959 effectively inhibited oxygen free radical formation by canine neutrophils. The results of this study show that CI-959 significantly reduces the myocardial infarct size without causing scar thinning, which might lead to ventricular aneurysm, and suggests the most likely mechanism for its beneficial action is the prevention of formation of toxic oxygen radicals."} {"id": "PMID:1280720", "title": "Beneficial effects of a new prostacyclin analogue, KP-10614, on acute myocardial infarction in rats.", "content": "The potential therapeutic value of a new prostacyclin analogue, (4z, 16s)-4,5,18,18,19,19-hexadehydro-16,20-dimethyl-delta 6(9a)- 9-(O)-methano-PGI1 (KP-10614), was studied in acute myocardial infarction in rats. Myocardial infarction was induced by ligation of the left coronary artery and ischemic injury was followed up to 4 h. The infarct size, evaluated by the area unstained by 2,3,5-triphenyltetrazolium chloride, reached 41.1 +/- 1.4% of the left ventricle at 4 h. KP-10614 (3 ng/kg/min x 4 h) reduced the infarct size at 4 h significantly (26.5 +/- 2.9%). At the same dose, KP-10614 inhibited ADP-induced ex vivo platelet aggregation significantly (21.5 +/- 4.0% of the control aggregation), but did not alter the arterial blood pressure or heart rate. To assess the role of platelets in myocardial infarction, circulating platelets were reduced by about 95% with rabbit antiserum to rat platelets. In platelet-depleted rats, the infarct size decreased significantly to 24.1 +/- 4.6% of the left ventricle at 4 h. These results suggest that platelets play an important role in expression of myocardial ischemic injury resulting from coronary artery occlusion in rats, and the ability of KP-10614 to decrease the infarct size appeared to be attributable, at least in part, to the inhibition of platelet aggregation or cellular metabolic effects produced by platelets at the site of tissue injury.", "contents": "Beneficial effects of a new prostacyclin analogue, KP-10614, on acute myocardial infarction in rats. The potential therapeutic value of a new prostacyclin analogue, (4z, 16s)-4,5,18,18,19,19-hexadehydro-16,20-dimethyl-delta 6(9a)- 9-(O)-methano-PGI1 (KP-10614), was studied in acute myocardial infarction in rats. Myocardial infarction was induced by ligation of the left coronary artery and ischemic injury was followed up to 4 h. The infarct size, evaluated by the area unstained by 2,3,5-triphenyltetrazolium chloride, reached 41.1 +/- 1.4% of the left ventricle at 4 h. KP-10614 (3 ng/kg/min x 4 h) reduced the infarct size at 4 h significantly (26.5 +/- 2.9%). At the same dose, KP-10614 inhibited ADP-induced ex vivo platelet aggregation significantly (21.5 +/- 4.0% of the control aggregation), but did not alter the arterial blood pressure or heart rate. To assess the role of platelets in myocardial infarction, circulating platelets were reduced by about 95% with rabbit antiserum to rat platelets. In platelet-depleted rats, the infarct size decreased significantly to 24.1 +/- 4.6% of the left ventricle at 4 h. These results suggest that platelets play an important role in expression of myocardial ischemic injury resulting from coronary artery occlusion in rats, and the ability of KP-10614 to decrease the infarct size appeared to be attributable, at least in part, to the inhibition of platelet aggregation or cellular metabolic effects produced by platelets at the site of tissue injury."} {"id": "PMID:1280721", "title": "Diltiazem potentiates angiotensin II-mediated renal prostacyclin synthesis.", "content": "Diltiazem (DIL), a calcium antagonist, has variable effects on renal hemodynamics, and has been considered to act independently of renal prostaglandins (PGs). Angiotensin II (AII) constricts renal vasculature but also increases renal vasodilator PG synthesis. We examined interactions between AII and DIL on [14C]p-aminohippurate ([14C]PAH) clearance, mean arterial pressure (MAP), and urine 6-ketoprostaglandin F1 alpha excretion (U6k) in groups of seven to nine conscious Sprague-Dawley rats. We calculated the renal vascular resistance (RVR) as the ratio of MAP/[14C]PAH clearance. AII infusion (10 ng/kg/min i.v.) increased the RVR by 50-80% for at least 120 min. DIL (1 mg/kg plus 2 micrograms/kg/min) reversed this vasoconstriction but adding indomethacin to DIL prevented the reversal. DIL alone did not change the RVR at 30-60 min after starting an infusion but increased it by 22% at 90-120 min. Adding AII to the DIL infusion actually decreased the RVR and this decrease was abolished by indomethacin. DIL alone had no effect on U6k while AII increased it slightly (1.36 +/- 0.12 to 1.86 +/- 0.22 ng/30 min, n = 6, p less than 0.05), and adding DIL to AII increased it further (3.19 ng/30 min, n = 6, p less than 0.05). We conclude that DIL enhances AII-induced renal prostacyclin synthesis and that this is functionally relevant. This mechanism may explain the reported variability of the renal hemodynamic effects of DIL. Furthermore, DIL-enhanced renal vasodilator PG synthesis may help protect the kidney during vasoconstrictor stress.", "contents": "Diltiazem potentiates angiotensin II-mediated renal prostacyclin synthesis. Diltiazem (DIL), a calcium antagonist, has variable effects on renal hemodynamics, and has been considered to act independently of renal prostaglandins (PGs). Angiotensin II (AII) constricts renal vasculature but also increases renal vasodilator PG synthesis. We examined interactions between AII and DIL on [14C]p-aminohippurate ([14C]PAH) clearance, mean arterial pressure (MAP), and urine 6-ketoprostaglandin F1 alpha excretion (U6k) in groups of seven to nine conscious Sprague-Dawley rats. We calculated the renal vascular resistance (RVR) as the ratio of MAP/[14C]PAH clearance. AII infusion (10 ng/kg/min i.v.) increased the RVR by 50-80% for at least 120 min. DIL (1 mg/kg plus 2 micrograms/kg/min) reversed this vasoconstriction but adding indomethacin to DIL prevented the reversal. DIL alone did not change the RVR at 30-60 min after starting an infusion but increased it by 22% at 90-120 min. Adding AII to the DIL infusion actually decreased the RVR and this decrease was abolished by indomethacin. DIL alone had no effect on U6k while AII increased it slightly (1.36 +/- 0.12 to 1.86 +/- 0.22 ng/30 min, n = 6, p less than 0.05), and adding DIL to AII increased it further (3.19 ng/30 min, n = 6, p less than 0.05). We conclude that DIL enhances AII-induced renal prostacyclin synthesis and that this is functionally relevant. This mechanism may explain the reported variability of the renal hemodynamic effects of DIL. Furthermore, DIL-enhanced renal vasodilator PG synthesis may help protect the kidney during vasoconstrictor stress."} {"id": "PMID:1280722", "title": "The role of the renin-angiotensin system in the control of cell communication in the heart: effects of enalapril and angiotensin II.", "content": "The influence of the renin-angiotensin system on the control of cell communication was investigated in isolated ventricular cell pairs of adult rats. It was found that angiotensin II (1 microgram/ml) reduced the junctional conductance (gj) by about 55% within 20 s. This effect of angiotensin II was suppressed by DuP 753--an angiotensin receptor blocking agent. Enalapril (1 microgram/ml)--an angiotensin converting enzyme inhibitor--caused an increase in junctional conductance (106%) within 2 min. The effect of enalapril on gj was not related to activation of beta-adrenergic receptors or cAMP-dependent protein kinase. The effect of angiotensin II on gj was suppressed by staurosporine--a potent inhibitor of protein kinase C. This finding indicates that the peptide is changing gj through activation of protein kinase C. The increase in cell coupling caused by enalapril raises the possibility that the antiarrhythmic action of enalapril as well its effect in congestive heart failure are related to an increase in electrical synchronization of cardiac myocytes.", "contents": "The role of the renin-angiotensin system in the control of cell communication in the heart: effects of enalapril and angiotensin II. The influence of the renin-angiotensin system on the control of cell communication was investigated in isolated ventricular cell pairs of adult rats. It was found that angiotensin II (1 microgram/ml) reduced the junctional conductance (gj) by about 55% within 20 s. This effect of angiotensin II was suppressed by DuP 753--an angiotensin receptor blocking agent. Enalapril (1 microgram/ml)--an angiotensin converting enzyme inhibitor--caused an increase in junctional conductance (106%) within 2 min. The effect of enalapril on gj was not related to activation of beta-adrenergic receptors or cAMP-dependent protein kinase. The effect of angiotensin II on gj was suppressed by staurosporine--a potent inhibitor of protein kinase C. This finding indicates that the peptide is changing gj through activation of protein kinase C. The increase in cell coupling caused by enalapril raises the possibility that the antiarrhythmic action of enalapril as well its effect in congestive heart failure are related to an increase in electrical synchronization of cardiac myocytes."} {"id": "PMID:1280723", "title": "Prostacyclin and nitric oxide contribute to the vasodilator action of acetylcholine and bradykinin in the intact rabbit coronary bed.", "content": "The relative contribution of nitric oxide (NO) and cyclo-oxygenase products in the dilator response to equieffective doses of acetylcholine (ACh) and bradykinin (Bk) was studied in the isolated, saline-perfused rabbit heart under constant flow conditions. ACh (1 microM) and Bk (10 nM) induced a similar vasodilation, with a maximum reduction in coronary perfusion pressure (CPP) of 27 +/- 2%. The vasodilation induced by both agonists was associated with an enhanced release of 6-keto-PGF1 alpha from the coronary bed, with the Bk-induced increase in 6-keto-PGF1 alpha being threefold greater than that induced by ACh. The angiotensin converting enzyme (ACE) inhibitor ramiprilat (0.3 microM) selectively enhanced both the 6-keto-PGF1 alpha outflow and the dilator response to Bk. The B2-receptor antagonist Hoe 140 (0.1 microM) blocked both Bk effects. The cyclo-oxygenase inhibitor diclofenac (1 microM) halved the dilator response to Bk, but did not affect the vasodilation to ACh. Both agonists induced the release of NO, as assessed by the increase in cyclic GMP content of platelets passing through the vascular bed. However, ACh induced a 2.5-fold greater increase in platelet cyclic GMP content, compared to Bk. Treatment of hearts with NG-nitro-L-arginine (L-NNA, 30 microM) halved the ACh- and Bk-induced maximum reduction in CPP. Combined infusion of L-NNA and diclofenac completely blocked the dilator response to Bk, and inhibited the vasodilation to ACh more efficiently than L-NNA alone. We conclude that both NO and PGI2 contribute to the coronary dilator response to Bk and ACh in the rabbit Langendorff heart.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Prostacyclin and nitric oxide contribute to the vasodilator action of acetylcholine and bradykinin in the intact rabbit coronary bed. The relative contribution of nitric oxide (NO) and cyclo-oxygenase products in the dilator response to equieffective doses of acetylcholine (ACh) and bradykinin (Bk) was studied in the isolated, saline-perfused rabbit heart under constant flow conditions. ACh (1 microM) and Bk (10 nM) induced a similar vasodilation, with a maximum reduction in coronary perfusion pressure (CPP) of 27 +/- 2%. The vasodilation induced by both agonists was associated with an enhanced release of 6-keto-PGF1 alpha from the coronary bed, with the Bk-induced increase in 6-keto-PGF1 alpha being threefold greater than that induced by ACh. The angiotensin converting enzyme (ACE) inhibitor ramiprilat (0.3 microM) selectively enhanced both the 6-keto-PGF1 alpha outflow and the dilator response to Bk. The B2-receptor antagonist Hoe 140 (0.1 microM) blocked both Bk effects. The cyclo-oxygenase inhibitor diclofenac (1 microM) halved the dilator response to Bk, but did not affect the vasodilation to ACh. Both agonists induced the release of NO, as assessed by the increase in cyclic GMP content of platelets passing through the vascular bed. However, ACh induced a 2.5-fold greater increase in platelet cyclic GMP content, compared to Bk. Treatment of hearts with NG-nitro-L-arginine (L-NNA, 30 microM) halved the ACh- and Bk-induced maximum reduction in CPP. Combined infusion of L-NNA and diclofenac completely blocked the dilator response to Bk, and inhibited the vasodilation to ACh more efficiently than L-NNA alone. We conclude that both NO and PGI2 contribute to the coronary dilator response to Bk and ACh in the rabbit Langendorff heart.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280724", "title": "Endothelin-1 increases the pulmonary microvascular pressure and causes pulmonary edema in salt solution but not blood-perfused rat lungs.", "content": "Endothelin-1 (ET-1) is a potent vasoactive peptide that has been reported to cause lung edema. This study tested if the edemagenic effect of ET-1 is due to preferential venoconstriction and, if so, whether the site of resistance is similar with salt solution (PSS) and more physiologic blood perfusate. ET-1 caused concentration-dependent contraction of pulmonary arterial and venous rings, with an EC50 of 1.3 nM in artery and 0.6 nM in vein (p less than 0.05). In PSS-perfused lungs, 5 nM ET-1 caused a 7.0 +/- 0.8 torr pressor response that was associated with a 5.0 +/- 0.3 torr increase in microvascular pressure and a 530 +/- 20 mg increase in lung weight within 10 min. In contrast, KCl-treated lungs had an equivalent pressor response (7.4 +/- 1.1 torr), yet the microvascular pressure increased by only 2.5 +/- 0.4 torr (p less than 0.05 from ET-1) and the lung weight was unchanged. Meclofenamate did not prevent the effect of ET-1 on microvascular pressure or lung weight. In blood-perfused lungs, ET-1 caused a 7.3 +/- 0.1 torr pressor response but only a 2.0 +/- 0.5 torr increase in microvascular pressure and no increase in lung weight. ET-1 had no effect on permeability either of cultured endothelial cell monolayers or in the pulmonary microvasculature in vivo. We conclude that the edemagenic effect of ET-1 in PSS-perfused lungs is mediated through venoconstriction and an increase in microvascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Endothelin-1 increases the pulmonary microvascular pressure and causes pulmonary edema in salt solution but not blood-perfused rat lungs. Endothelin-1 (ET-1) is a potent vasoactive peptide that has been reported to cause lung edema. This study tested if the edemagenic effect of ET-1 is due to preferential venoconstriction and, if so, whether the site of resistance is similar with salt solution (PSS) and more physiologic blood perfusate. ET-1 caused concentration-dependent contraction of pulmonary arterial and venous rings, with an EC50 of 1.3 nM in artery and 0.6 nM in vein (p less than 0.05). In PSS-perfused lungs, 5 nM ET-1 caused a 7.0 +/- 0.8 torr pressor response that was associated with a 5.0 +/- 0.3 torr increase in microvascular pressure and a 530 +/- 20 mg increase in lung weight within 10 min. In contrast, KCl-treated lungs had an equivalent pressor response (7.4 +/- 1.1 torr), yet the microvascular pressure increased by only 2.5 +/- 0.4 torr (p less than 0.05 from ET-1) and the lung weight was unchanged. Meclofenamate did not prevent the effect of ET-1 on microvascular pressure or lung weight. In blood-perfused lungs, ET-1 caused a 7.3 +/- 0.1 torr pressor response but only a 2.0 +/- 0.5 torr increase in microvascular pressure and no increase in lung weight. ET-1 had no effect on permeability either of cultured endothelial cell monolayers or in the pulmonary microvasculature in vivo. We conclude that the edemagenic effect of ET-1 in PSS-perfused lungs is mediated through venoconstriction and an increase in microvascular pressure.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280725", "title": "Endothelin plasma levels in old and young patients during open heart surgery: correlations to cardiopulmonary and endocrinology parameters.", "content": "We compared endothelin (ET) plasma levels during and after aortocoronary bypass (CPB) grafting in old and young patients. Correlations to cardiopulmonary parameters and catecholamines were tested. The study included 22 patients (11 aged greater than 70 years and 11 aged less than 55 years). Measurements were performed after induction of anesthesia (baseline), before bypass, during bypass, after patients were weaned off bypass, at the end of operation, and after 4-h intensive care (IC) treatment. ET [radioimmunoassay (RIA) technique] and catecholamines [high pressure liquid chromatography (HPLC) technique] plasma levels were determined from arterial blood samples; hemodynamics (pulmonary artery catheter), oxygen data, and laser Doppler flow were also monitored. Baseline ET plasma levels were within normal range (young, 3.1 +/- 0.9 pg/ml, old, 4.5 +/- 1.4 pg/ml). Old patients had higher values during the entire investigation period. During CPB ET plasma levels increased to a maximum immediately after patients were weaned off bypass. A significant increase (twofold to baseline) was noted during IC therapy. ET plasma levels did not correlate to catecholamine plasma levels or to hemodynamic or laser Doppler flow parameters. A significant correlation existed between ET plasma levels and oxygen consumption. Monitoring ET plasma levels appears to be of minor value in predicting circulatory changes and assessing surgical stress. Further investigations must elucidate the increase in oxygen consumption and its correlation to ET plasma level.", "contents": "Endothelin plasma levels in old and young patients during open heart surgery: correlations to cardiopulmonary and endocrinology parameters. We compared endothelin (ET) plasma levels during and after aortocoronary bypass (CPB) grafting in old and young patients. Correlations to cardiopulmonary parameters and catecholamines were tested. The study included 22 patients (11 aged greater than 70 years and 11 aged less than 55 years). Measurements were performed after induction of anesthesia (baseline), before bypass, during bypass, after patients were weaned off bypass, at the end of operation, and after 4-h intensive care (IC) treatment. ET [radioimmunoassay (RIA) technique] and catecholamines [high pressure liquid chromatography (HPLC) technique] plasma levels were determined from arterial blood samples; hemodynamics (pulmonary artery catheter), oxygen data, and laser Doppler flow were also monitored. Baseline ET plasma levels were within normal range (young, 3.1 +/- 0.9 pg/ml, old, 4.5 +/- 1.4 pg/ml). Old patients had higher values during the entire investigation period. During CPB ET plasma levels increased to a maximum immediately after patients were weaned off bypass. A significant increase (twofold to baseline) was noted during IC therapy. ET plasma levels did not correlate to catecholamine plasma levels or to hemodynamic or laser Doppler flow parameters. A significant correlation existed between ET plasma levels and oxygen consumption. Monitoring ET plasma levels appears to be of minor value in predicting circulatory changes and assessing surgical stress. Further investigations must elucidate the increase in oxygen consumption and its correlation to ET plasma level."} {"id": "PMID:1280726", "title": "Evaluation of inotropic effect of endothelin-1 in vivo.", "content": "The vasoconstrictive peptide endothelin-1 (ET-1) has been reported to exert a very important positive inotropic effect in vitro. To assess the effect of ET-1 on myocardial contractility in vivo, we compared the effect of intracoronary infusion of 10(-8) M ET-1 (constant coronary blood flow) to that of 10(-8) M dobutamine in 8 swine. ET infusion did not produce changes in segmental shortening (control vs. drug, mean +/- SD): 33.8 +/- 14.3 vs. 30.8 +/- 12.1%, shortening velocity: 10.3 +/- 4.3 vs. 10.7 +/- 4.5 mm/s, or maximum +dP/dt: 1,691 +/- 701 vs. 1,772 +/- 773 mm Hg/s, whereas dobutamine infusion induced an important increase in these measurements; segmental shortening: 36.9 +/- 14 vs. 48.4 +/- 18.8%, shortening velocity: 10.1 +/- 2.6 vs. 14.7 +/- 4.5 mm/s, and maximum +dP/dt: 2,041 +/- 567 vs. 2,389 +/- 765 mm Hg/s (all p less than 0.05). Mean myocardial blood flow assessed by microspheres was unchanged by ET-1 despite a marked increase in coronary artery pressure (88.6 +/- 12.9 vs. 157 +/- 8.8 mm Hg, p less than 0.001). Regional infusion of ET-1 at a dose provoking extensive coronary vasoconstriction does not induce any change in regional or global myocardial function in swine.", "contents": "Evaluation of inotropic effect of endothelin-1 in vivo. The vasoconstrictive peptide endothelin-1 (ET-1) has been reported to exert a very important positive inotropic effect in vitro. To assess the effect of ET-1 on myocardial contractility in vivo, we compared the effect of intracoronary infusion of 10(-8) M ET-1 (constant coronary blood flow) to that of 10(-8) M dobutamine in 8 swine. ET infusion did not produce changes in segmental shortening (control vs. drug, mean +/- SD): 33.8 +/- 14.3 vs. 30.8 +/- 12.1%, shortening velocity: 10.3 +/- 4.3 vs. 10.7 +/- 4.5 mm/s, or maximum +dP/dt: 1,691 +/- 701 vs. 1,772 +/- 773 mm Hg/s, whereas dobutamine infusion induced an important increase in these measurements; segmental shortening: 36.9 +/- 14 vs. 48.4 +/- 18.8%, shortening velocity: 10.1 +/- 2.6 vs. 14.7 +/- 4.5 mm/s, and maximum +dP/dt: 2,041 +/- 567 vs. 2,389 +/- 765 mm Hg/s (all p less than 0.05). Mean myocardial blood flow assessed by microspheres was unchanged by ET-1 despite a marked increase in coronary artery pressure (88.6 +/- 12.9 vs. 157 +/- 8.8 mm Hg, p less than 0.001). Regional infusion of ET-1 at a dose provoking extensive coronary vasoconstriction does not induce any change in regional or global myocardial function in swine."} {"id": "PMID:1280727", "title": "Comparative cardiovascular actions of clentiazem, diltiazem, verapamil, nifedipine, and nimodipine in isolated rabbit tissues.", "content": "Clentiazem is an 8-chloro-substituted derivative of diltiazem. We compared the relative potency of clentiazem with that of diltiazem, verapamil, nifedipine, and nimodipine in isolated rabbit right atria and vascular smooth muscle removed from various arterial beds. In experiments with isolated right atria, calcium channel blockers were added cumulatively to study relative cardiodepressive potencies (as compared with vascular effects) with the following results: verapamil greater than or equal to diltiazem greater than clentiazem greater than or equal to nimodipine much greater than nifedipine. The aorta, pulmonary, renal, mesenteric, coronary, and basilar arteries were removed, cut helically in strips, and mounted in isolated tissue baths to measure isometric force. Vessels were contracted with either 40 mM KCl (opening voltage-operated calcium channels) or 1 x 10(-5) M norepinephrine (NE, opening receptor-operated calcium channels). Cumulative dose-response curves were generated for relaxation with each calcium channel blocker. All compounds were more potent at relaxing potassium-induced contractions than NE-induced contractions. In vessels precontracted with KCl, neither diltiazem, verapamil, or nifedipine showed selectivity for basilar artery as compared with the mesenteric artery. Both clentiazem and nimodipine were selective (6- and 30-fold, respectively) for basilar artery in blocking potassium-induced contractions. When NE was used to contract the arteries, clentiazem (12-fold), diltiazem (8-fold), verapamil (8-fold), and nifedipine (153-fold) were all more potent in relaxing the contraction in basilar artery than in mesenteric artery. Nimodipine failed to demonstrate selectivity for basilar artery as compared with mesenteric artery contracted with NE.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Comparative cardiovascular actions of clentiazem, diltiazem, verapamil, nifedipine, and nimodipine in isolated rabbit tissues. Clentiazem is an 8-chloro-substituted derivative of diltiazem. We compared the relative potency of clentiazem with that of diltiazem, verapamil, nifedipine, and nimodipine in isolated rabbit right atria and vascular smooth muscle removed from various arterial beds. In experiments with isolated right atria, calcium channel blockers were added cumulatively to study relative cardiodepressive potencies (as compared with vascular effects) with the following results: verapamil greater than or equal to diltiazem greater than clentiazem greater than or equal to nimodipine much greater than nifedipine. The aorta, pulmonary, renal, mesenteric, coronary, and basilar arteries were removed, cut helically in strips, and mounted in isolated tissue baths to measure isometric force. Vessels were contracted with either 40 mM KCl (opening voltage-operated calcium channels) or 1 x 10(-5) M norepinephrine (NE, opening receptor-operated calcium channels). Cumulative dose-response curves were generated for relaxation with each calcium channel blocker. All compounds were more potent at relaxing potassium-induced contractions than NE-induced contractions. In vessels precontracted with KCl, neither diltiazem, verapamil, or nifedipine showed selectivity for basilar artery as compared with the mesenteric artery. Both clentiazem and nimodipine were selective (6- and 30-fold, respectively) for basilar artery in blocking potassium-induced contractions. When NE was used to contract the arteries, clentiazem (12-fold), diltiazem (8-fold), verapamil (8-fold), and nifedipine (153-fold) were all more potent in relaxing the contraction in basilar artery than in mesenteric artery. Nimodipine failed to demonstrate selectivity for basilar artery as compared with mesenteric artery contracted with NE.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280728", "title": "Short-term effects of celiprolol on blood pressure and left ventricular performance in hypertensive cardiomyopathy.", "content": "Celiprolol (C) is a new selective beta 1-blocker with partial beta 2-agonistic activity. The purpose of this study was to explore its antihypertensive efficacy and its short-term effect on systemic vascular resistances (SVR), cardiac output (CO), left ventricular ejection fraction (LVEF), and left ventricular diastolic performance (LVDP). The Doppler technique was used. In an open-label study, 20 hypertensive patients (15 males, 5 females, age range of 29-68 years) with left ventricular hypertrophy detected by echography were daily treated with 400 mg of C in a single dose, for a period of 4 weeks. C reduced significantly the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) (158 +/- 12 vs. 142 +/- 11 mm Hg, p < 0.05 and 101 +/- 6 vs. 87 +/- 4 mm Hg, p < 0.001, respectively) with a decrease in heart rate (74 +/- 12 vs. 67 +/- 8 beats/min, p = NS). The SVR decreased significantly (2,050 +/- 22 vs. 1,495 +/- 23 dyn/s/cm5, p < 0.001) with a slight but not significant increase in the CO (4.5 +/- 0.69 vs. 5.11 +/- 0.82 L/min). The LVEF did not decrease significantly (58 +/- 5 vs. 56.9 +/- 6%, p = NS) while the LVDP was modified favorably, significantly reducing the early diastolic deceleration time (EDDT) (199 +/- 61 vs. 132 +/- 80 ms, p < 0.01) and reducing the isovolumetric relaxation time (IVRT) (167 +/- 16 vs. 117 +/- 23 ms, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Short-term effects of celiprolol on blood pressure and left ventricular performance in hypertensive cardiomyopathy. Celiprolol (C) is a new selective beta 1-blocker with partial beta 2-agonistic activity. The purpose of this study was to explore its antihypertensive efficacy and its short-term effect on systemic vascular resistances (SVR), cardiac output (CO), left ventricular ejection fraction (LVEF), and left ventricular diastolic performance (LVDP). The Doppler technique was used. In an open-label study, 20 hypertensive patients (15 males, 5 females, age range of 29-68 years) with left ventricular hypertrophy detected by echography were daily treated with 400 mg of C in a single dose, for a period of 4 weeks. C reduced significantly the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) (158 +/- 12 vs. 142 +/- 11 mm Hg, p < 0.05 and 101 +/- 6 vs. 87 +/- 4 mm Hg, p < 0.001, respectively) with a decrease in heart rate (74 +/- 12 vs. 67 +/- 8 beats/min, p = NS). The SVR decreased significantly (2,050 +/- 22 vs. 1,495 +/- 23 dyn/s/cm5, p < 0.001) with a slight but not significant increase in the CO (4.5 +/- 0.69 vs. 5.11 +/- 0.82 L/min). The LVEF did not decrease significantly (58 +/- 5 vs. 56.9 +/- 6%, p = NS) while the LVDP was modified favorably, significantly reducing the early diastolic deceleration time (EDDT) (199 +/- 61 vs. 132 +/- 80 ms, p < 0.01) and reducing the isovolumetric relaxation time (IVRT) (167 +/- 16 vs. 117 +/- 23 ms, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280729", "title": "Contrasting influences of central and peripheral opioids on cardiac baroreflex sensitivity in rabbits.", "content": "We studied the effects of naloxone [0.1 mg/kg intravenously (i.v.) or 7.5 micrograms/kg intracisternally (i.c.)], naloxone methyl iodide (NMI, 0.2 mg/kg, i.v. or 15 micrograms/kg i.c.) and morphine (2 mg/kg i.v.) on the cardiac baroreflex elicited in conscious rabbits especially bred for high and low baroreflex sensitivity (BRS) (group I, BRS > 5.5 beats/min/mm Hg and group II BRS < 4 beats/min/mm Hg, respectively). Full sigmoid barocurves were produced in 37 rabbits by i.v. injection of phenylephrine (1-15 micrograms/kg) and nitroglycerin (1-20 micrograms/kg) after pretreatment with saline or one of the above drugs. In group I, both naloxone i.v. and i.c. and NMI i.c. significantly reduced BRS and decreased the degree of bradycardia in response to a pressor stimulus; neither morphine nor NMI i.v. had any effect. In group II, naloxone i.v. and i.c. and NMI i.c. had no effect on BRS, but both morphine and NMI i.v. significantly increased BRS. An even greater increase was achieved by a combination of these drugs, which also increased specifically the degree of tachycardia in response to a decrease in blood pressure (BP). The results suggest that baroreceptor activation in group I released in the brainstem an opioid peptide that acts to increase BRS. In contrast, group II rabbits responded by peripheral opioid activation, which results in a decrease in BRS, possibly by inhibiting norepinephrine (NE) release from cardiac neurons. The predominance of peripheral or central opioid involvement in BRS modulation appears to be due to genetic factors.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Contrasting influences of central and peripheral opioids on cardiac baroreflex sensitivity in rabbits. We studied the effects of naloxone [0.1 mg/kg intravenously (i.v.) or 7.5 micrograms/kg intracisternally (i.c.)], naloxone methyl iodide (NMI, 0.2 mg/kg, i.v. or 15 micrograms/kg i.c.) and morphine (2 mg/kg i.v.) on the cardiac baroreflex elicited in conscious rabbits especially bred for high and low baroreflex sensitivity (BRS) (group I, BRS > 5.5 beats/min/mm Hg and group II BRS < 4 beats/min/mm Hg, respectively). Full sigmoid barocurves were produced in 37 rabbits by i.v. injection of phenylephrine (1-15 micrograms/kg) and nitroglycerin (1-20 micrograms/kg) after pretreatment with saline or one of the above drugs. In group I, both naloxone i.v. and i.c. and NMI i.c. significantly reduced BRS and decreased the degree of bradycardia in response to a pressor stimulus; neither morphine nor NMI i.v. had any effect. In group II, naloxone i.v. and i.c. and NMI i.c. had no effect on BRS, but both morphine and NMI i.v. significantly increased BRS. An even greater increase was achieved by a combination of these drugs, which also increased specifically the degree of tachycardia in response to a decrease in blood pressure (BP). The results suggest that baroreceptor activation in group I released in the brainstem an opioid peptide that acts to increase BRS. In contrast, group II rabbits responded by peripheral opioid activation, which results in a decrease in BRS, possibly by inhibiting norepinephrine (NE) release from cardiac neurons. The predominance of peripheral or central opioid involvement in BRS modulation appears to be due to genetic factors.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280730", "title": "Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: insight into its mechanism of action.", "content": "We assessed whether local inhibition of myocardial converting enzyme by captopril and zofenopril reduces the functional and metabolic damage caused by ischemia and reperfusion. First we investigated the effects of zofenopril and captopril on the mechanical function, cellular redox state, and norepinephrine (NE) content of isolated and aerobically perfused rabbit hearts. Both drugs failed to modify the myocardial redox state. At concentrations > 10(-6) M, zofenopril, but not captopril, caused a reduction in myocardial NE content. At 10(-4) M, both drugs caused a reduction in developed pressure and an increase in diastolic pressure and release of creatine phosphokinase (CPK). Second we investigated their effects on ischemic and reperfused myocardium. Both drugs exerted a cardioprotection; zofenopril was always more potent than captopril. Recovery of developed pressure on reperfusion improved, and peak release of NE was reduced, as was release of CPK. Calcium homeostasis and mitochondrial function were maintained. Captopril had no effect on occurrence of oxidative stress during reperfusion, whereas zofenopril reduced it. In hearts treated with the converting enzyme inhibitors, peak release of NE was correlated to mitochondrial calcium content, production of ATP, and recovery of mechanical function on reperfusion. These data suggest that the cardioprotective effect of zofenopril and captopril is independent of hemodynamic changes or reduction of the toxicity of oxygen free radicals and that it could be related to a reduction in release of NE.", "contents": "Protection of the ischemic myocardium by the converting-enzyme inhibitor zofenopril: insight into its mechanism of action. We assessed whether local inhibition of myocardial converting enzyme by captopril and zofenopril reduces the functional and metabolic damage caused by ischemia and reperfusion. First we investigated the effects of zofenopril and captopril on the mechanical function, cellular redox state, and norepinephrine (NE) content of isolated and aerobically perfused rabbit hearts. Both drugs failed to modify the myocardial redox state. At concentrations > 10(-6) M, zofenopril, but not captopril, caused a reduction in myocardial NE content. At 10(-4) M, both drugs caused a reduction in developed pressure and an increase in diastolic pressure and release of creatine phosphokinase (CPK). Second we investigated their effects on ischemic and reperfused myocardium. Both drugs exerted a cardioprotection; zofenopril was always more potent than captopril. Recovery of developed pressure on reperfusion improved, and peak release of NE was reduced, as was release of CPK. Calcium homeostasis and mitochondrial function were maintained. Captopril had no effect on occurrence of oxidative stress during reperfusion, whereas zofenopril reduced it. In hearts treated with the converting enzyme inhibitors, peak release of NE was correlated to mitochondrial calcium content, production of ATP, and recovery of mechanical function on reperfusion. These data suggest that the cardioprotective effect of zofenopril and captopril is independent of hemodynamic changes or reduction of the toxicity of oxygen free radicals and that it could be related to a reduction in release of NE."} {"id": "PMID:1280731", "title": "In vitro pharmacology of R 80122, a novel phosphodiesterase inhibitor.", "content": "The cardiac in vitro effects of R 80122, a novel phosphodiesterase (PDE) inhibitor, were investigated and compared with those of the reference compound milrinone and of the calcium-sensitizer adibendan. In guinea pig left atria, both milrinone and R 80122 increased contractile force; 10 microM milrinone was equieffective to 1 microM R 80122. The rate of spontaneously beating atria was not altered by R 80122 in the concentration range of 0.01-0.3 microM. Higher concentrations (1-10 microM) led to a statistically insignificant increase of 20%. Milrinone's effect on frequency was more pronounced and amounted to 21% at 10 microM and to 40% at 100 microM. Adibendan increased heart rate (HR) by 10% at a concentration of only 0.03 microM. This effect was not enhanced any further by increasing the concentration. In papillary muscle, the positive inotropic effects of both milrinone and R 80122 were inhibited by carbachol, indicating involvement of cyclic AMP. Further indications for a cyclic AMP-dependent action were obtained by induction of slow action potentials and synergism with isoprenaline. In electrophysiologic measurements, milrinone reduced action potential duration (APD) in a high concentration whereas R 80122 had no effect. Action potential changes elicited by a toxic concentration of ouabain were reduced by R 80122. Relaxation of rat aortic rings contracted by KCl and relaxation of guinea pig aortic rings contracted by norepinephrine (NE) was comparable for both milrinone and R 80122. R 80122 also caused relaxation of canine coronary arteries constricted with prostaglandin F2 alpha (PGF2 alpha) both with and without endothelium. NE-induced contractions in canine gastrosplenic arteries were not affected by R 80122. Cardiac contractility that had been impaired to various degrees by pentobarbital or by aging was restored to control values by both milrinone and R 80122. R 80122 enhanced cardiac contractility at lower concentrations than milrinone with no concomitant increase in frequency or shortening of the action potential, which may be advantageous for treatment of heart failure.", "contents": "In vitro pharmacology of R 80122, a novel phosphodiesterase inhibitor. The cardiac in vitro effects of R 80122, a novel phosphodiesterase (PDE) inhibitor, were investigated and compared with those of the reference compound milrinone and of the calcium-sensitizer adibendan. In guinea pig left atria, both milrinone and R 80122 increased contractile force; 10 microM milrinone was equieffective to 1 microM R 80122. The rate of spontaneously beating atria was not altered by R 80122 in the concentration range of 0.01-0.3 microM. Higher concentrations (1-10 microM) led to a statistically insignificant increase of 20%. Milrinone's effect on frequency was more pronounced and amounted to 21% at 10 microM and to 40% at 100 microM. Adibendan increased heart rate (HR) by 10% at a concentration of only 0.03 microM. This effect was not enhanced any further by increasing the concentration. In papillary muscle, the positive inotropic effects of both milrinone and R 80122 were inhibited by carbachol, indicating involvement of cyclic AMP. Further indications for a cyclic AMP-dependent action were obtained by induction of slow action potentials and synergism with isoprenaline. In electrophysiologic measurements, milrinone reduced action potential duration (APD) in a high concentration whereas R 80122 had no effect. Action potential changes elicited by a toxic concentration of ouabain were reduced by R 80122. Relaxation of rat aortic rings contracted by KCl and relaxation of guinea pig aortic rings contracted by norepinephrine (NE) was comparable for both milrinone and R 80122. R 80122 also caused relaxation of canine coronary arteries constricted with prostaglandin F2 alpha (PGF2 alpha) both with and without endothelium. NE-induced contractions in canine gastrosplenic arteries were not affected by R 80122. Cardiac contractility that had been impaired to various degrees by pentobarbital or by aging was restored to control values by both milrinone and R 80122. R 80122 enhanced cardiac contractility at lower concentrations than milrinone with no concomitant increase in frequency or shortening of the action potential, which may be advantageous for treatment of heart failure."} {"id": "PMID:1280732", "title": "Effects of a cardiotonic quinolinone derivative Y-20487 on the isoproterenol-induced positive inotropic action and cyclic AMP accumulation in rat ventricular myocardium: comparison with rolipram, Ro 20-1724, milrinone, and isobutylmethylxanthine.", "content": "The effect of a new cardiotonic agent Y-20487 [6-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-3,4-dihydro-2(1H)- quinolinone] on cyclic AMP levels of rat ventricular cardiomyocytes and the contractile force of papillary muscles was investigated in comparison with selective cyclic AMP phosphodiesterase (PDE) inhibitors, milrinone (PDE-III selective), rolipram and Ro 20-1724 (PDE-IV selective), and a nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX). Rolipram and Ro 20-1724 did not elicit cyclic AMP accumulation and positive inotropy, but they potentiated the isoproterenol (ISO)-induced cyclic AMP accumulation more effectively than IBMX. Rolipram was more effective than Ro 20-1724 in enhancing ISO-induced cyclic AMP accumulation but was less effective in enhancing the ISO-induced positive inotropic effect, indicating that these agents produce a differential action on cyclic AMP metabolism and inotropy. Milrinone and Y-20487 elicited cyclic AMP accumulation and positive inotropy by themselves. Whereas milrinone scarcely affected the ISO-induced effects, Y-20487 shifted the concentration-response curve for the positive inotropic effect of ISO to the left to the same extent that IBMX did. Y-20487, however, was much less effective than IBMX in enhancing the ISO-induced cyclic AMP accumulation. The present results indicate that in rat ventricular myocardium, PDE-IV may play a crucial role in breakdown of cyclic AMP generated by beta-adrenoceptor stimulation, whereas other types of PDE isoenzymes, including PDE-III, may be responsible for the cyclic AMP accumulation and direct positive inotropic effect induced by PDE inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of a cardiotonic quinolinone derivative Y-20487 on the isoproterenol-induced positive inotropic action and cyclic AMP accumulation in rat ventricular myocardium: comparison with rolipram, Ro 20-1724, milrinone, and isobutylmethylxanthine. The effect of a new cardiotonic agent Y-20487 [6-(3,6-dihydro-2-oxo-2H-1,3,4-thiadiazin-5-yl)-3,4-dihydro-2(1H)- quinolinone] on cyclic AMP levels of rat ventricular cardiomyocytes and the contractile force of papillary muscles was investigated in comparison with selective cyclic AMP phosphodiesterase (PDE) inhibitors, milrinone (PDE-III selective), rolipram and Ro 20-1724 (PDE-IV selective), and a nonselective inhibitor 3-isobutyl-1-methylxanthine (IBMX). Rolipram and Ro 20-1724 did not elicit cyclic AMP accumulation and positive inotropy, but they potentiated the isoproterenol (ISO)-induced cyclic AMP accumulation more effectively than IBMX. Rolipram was more effective than Ro 20-1724 in enhancing ISO-induced cyclic AMP accumulation but was less effective in enhancing the ISO-induced positive inotropic effect, indicating that these agents produce a differential action on cyclic AMP metabolism and inotropy. Milrinone and Y-20487 elicited cyclic AMP accumulation and positive inotropy by themselves. Whereas milrinone scarcely affected the ISO-induced effects, Y-20487 shifted the concentration-response curve for the positive inotropic effect of ISO to the left to the same extent that IBMX did. Y-20487, however, was much less effective than IBMX in enhancing the ISO-induced cyclic AMP accumulation. The present results indicate that in rat ventricular myocardium, PDE-IV may play a crucial role in breakdown of cyclic AMP generated by beta-adrenoceptor stimulation, whereas other types of PDE isoenzymes, including PDE-III, may be responsible for the cyclic AMP accumulation and direct positive inotropic effect induced by PDE inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280733", "title": "Antihypertensive effects of MPC-1304, a novel calcium antagonist, in experimental hypertensive rats and dogs.", "content": "Antihypertensive effects of a novel calcium antagonist, MPC-1304, (+-)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5- pyridine-dicarboxylate and its active metabolites were investigated in experimental hypertensive rats and dogs and compared with those of other dihydropyridine derivatives (nifedipine, nisoldipine, nicardipine, and nitrendipine). MPC-1304 had a dose-related antihypertensive effect with a slight increase in heart rate (HR) in rats. The antihypertensive effects of MPC-1304 were more potent than those of other dihydropyridines, and its active metabolites had antihypertensive effects comparable to those of other dihydropyridines. The hypotensive effects of MPC-1304 were stronger in hypertensive rats than in normotensive rats. During repeated oral administration of MPC-1304 to spontaneously hypertensive rats (SHR, once daily for 4 weeks, 0.3-3 mg/kg), dose-response curves of the antihypertensive effect did not change and body weight gain was equal to that of the vehicle-treated group. When given orally to conscious renal hypertensive dogs, MPC-1304 0.1-0.3 mg/kg had a potency and duration of antihypertensive action comparable to that of nitrendipine (1-3 mg/kg). MPC-1304 increased coronary blood flow (CBF) and aortic blood flow (ABF) in conscious normotensive dogs. In conclusion, MPC-1304 and its active metabolites have potent antihypertensive effects and cause slight tachycardia, and they may be useful in treating hypertension.", "contents": "Antihypertensive effects of MPC-1304, a novel calcium antagonist, in experimental hypertensive rats and dogs. Antihypertensive effects of a novel calcium antagonist, MPC-1304, (+-)-methyl 2-oxopropyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5- pyridine-dicarboxylate and its active metabolites were investigated in experimental hypertensive rats and dogs and compared with those of other dihydropyridine derivatives (nifedipine, nisoldipine, nicardipine, and nitrendipine). MPC-1304 had a dose-related antihypertensive effect with a slight increase in heart rate (HR) in rats. The antihypertensive effects of MPC-1304 were more potent than those of other dihydropyridines, and its active metabolites had antihypertensive effects comparable to those of other dihydropyridines. The hypotensive effects of MPC-1304 were stronger in hypertensive rats than in normotensive rats. During repeated oral administration of MPC-1304 to spontaneously hypertensive rats (SHR, once daily for 4 weeks, 0.3-3 mg/kg), dose-response curves of the antihypertensive effect did not change and body weight gain was equal to that of the vehicle-treated group. When given orally to conscious renal hypertensive dogs, MPC-1304 0.1-0.3 mg/kg had a potency and duration of antihypertensive action comparable to that of nitrendipine (1-3 mg/kg). MPC-1304 increased coronary blood flow (CBF) and aortic blood flow (ABF) in conscious normotensive dogs. In conclusion, MPC-1304 and its active metabolites have potent antihypertensive effects and cause slight tachycardia, and they may be useful in treating hypertension."} {"id": "PMID:1280734", "title": "Effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery in miniature pigs.", "content": "The effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery was examined in miniature pigs. A diffuse intimal thickening was observed in vehicle-treated controls 6 weeks after balloon catheterization. The histologic features of the intimal thickening resembled those of early atherosclerotic lesions and restenosis after percutaneous transluminal coronary angioplasty (PTCA). Nilvadipine given in a daily dose of 10 mg/kg (subcutaneously, s.c.) for 6 weeks significantly inhibited intimal thickening. The ratio of the cross-sectional area of the intima to the cross-sectional area of the media was significantly reduced by 62% in nilvadipine-treated animals. These results suggest that nilvadipine may prevent or exert beneficial effects on coronary arterial injuries such as atherosclerosis and restenosis after PTCA.", "contents": "Effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery in miniature pigs. The effect of nilvadipine on balloon catheterization-induced intimal thickening of the coronary artery was examined in miniature pigs. A diffuse intimal thickening was observed in vehicle-treated controls 6 weeks after balloon catheterization. The histologic features of the intimal thickening resembled those of early atherosclerotic lesions and restenosis after percutaneous transluminal coronary angioplasty (PTCA). Nilvadipine given in a daily dose of 10 mg/kg (subcutaneously, s.c.) for 6 weeks significantly inhibited intimal thickening. The ratio of the cross-sectional area of the intima to the cross-sectional area of the media was significantly reduced by 62% in nilvadipine-treated animals. These results suggest that nilvadipine may prevent or exert beneficial effects on coronary arterial injuries such as atherosclerosis and restenosis after PTCA."} {"id": "PMID:1280735", "title": "Acute inhibition of endopeptidase 24.11 in essential hypertension: SCH 34826 enhances atrial natriuretic peptide and natriuresis without lowering blood pressure.", "content": "The acute renal, endocrine, and hemodynamic effects of the orally active endopeptidase inhibitor SCH 34826 (400 mg every 6 hours for five doses) were investigated in a group of 6 male patients [with established mild to moderate essential hypertension and left ventricular (LV) hypertrophy] in a balanced random-order double-blind, placebo-controlled cross-over study. Plasma atrial natriuretic factor (ANF) concentrations increased (p < 0.05) to fourfold control values after the first dose of inhibitor, but later postdose increments of ANF were less pronounced. Plasma cyclic GMP also increased significantly (p < 0.05). These effects were associated with a transient modest but significant (p < 0.05) increase in sodium excretion (50 mmol sodium in excess of placebo values) that was complete in 24 h. Mean 24-h urinary excretions of cyclic GMP and immunoreactive ANF were also significantly increased by 55 and 86%, respectively. Other urine indexes (including other electrolytes, volume, creatinine, aldosterone, and cortisol) and renal hemodynamics [including glomerular filtration rate (GFR) and effective renal plasma flow (RPF)] were unchanged. Renin-angiotensin-aldosterone system (RAAS) activity was not significantly altered. Plasma epinephrine increased after the initial three doses of SCH 34826. Systolic blood pressure (SBP) and heart rate (HR) were not altered by SCH 34826. Diastolic BP (DBP) increased slightly (p = 0.044). Acute inhibition of endopeptidase 24.11 by SCH 34826 in essential hypertension caused significant increments in plasma ANF and cyclic GMP together with modest natriuresis. No antihypertensive effect was observed in the first 30 h of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Acute inhibition of endopeptidase 24.11 in essential hypertension: SCH 34826 enhances atrial natriuretic peptide and natriuresis without lowering blood pressure. The acute renal, endocrine, and hemodynamic effects of the orally active endopeptidase inhibitor SCH 34826 (400 mg every 6 hours for five doses) were investigated in a group of 6 male patients [with established mild to moderate essential hypertension and left ventricular (LV) hypertrophy] in a balanced random-order double-blind, placebo-controlled cross-over study. Plasma atrial natriuretic factor (ANF) concentrations increased (p < 0.05) to fourfold control values after the first dose of inhibitor, but later postdose increments of ANF were less pronounced. Plasma cyclic GMP also increased significantly (p < 0.05). These effects were associated with a transient modest but significant (p < 0.05) increase in sodium excretion (50 mmol sodium in excess of placebo values) that was complete in 24 h. Mean 24-h urinary excretions of cyclic GMP and immunoreactive ANF were also significantly increased by 55 and 86%, respectively. Other urine indexes (including other electrolytes, volume, creatinine, aldosterone, and cortisol) and renal hemodynamics [including glomerular filtration rate (GFR) and effective renal plasma flow (RPF)] were unchanged. Renin-angiotensin-aldosterone system (RAAS) activity was not significantly altered. Plasma epinephrine increased after the initial three doses of SCH 34826. Systolic blood pressure (SBP) and heart rate (HR) were not altered by SCH 34826. Diastolic BP (DBP) increased slightly (p = 0.044). Acute inhibition of endopeptidase 24.11 by SCH 34826 in essential hypertension caused significant increments in plasma ANF and cyclic GMP together with modest natriuresis. No antihypertensive effect was observed in the first 30 h of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280736", "title": "Effects of S-dobutamine on venous blood return and organ nutrient blood flow.", "content": "The selective contractile effects of s-dobutamine were studied in vitro in selected canine arteries and vein preparations; propranolol was included to block potential beta-mediated vasodilation. These in vitro data were expanded by quantifying the in vivo effects of s-dobutamine on venous blood return and redistribution of regional nutrient blood flow (NBF) and non-nutrient blood flow (non-NBF) in anesthetized dogs. In in vitro studies with isolated canine arteries and veins, s-dobutamine exhibited vein-selective constriction. At maximally efficacious concentrations of agonist, contractions of carotid, coronary, and femoral arteries in response to s-dobutamine were only 7, 25 and 45% as great as those elicited by norepinephrine (NE). Similarly, in jugular vein, s-dobutamine-mediated contractions were 55% as great as those obtained in response to NE. Coronary and femoral arteries precontracted with NE were relaxed in a dose-related manner by increasing concentrations of s-dobutamine. Effects of NE and s-dobutamine on venous blood return (VR) were compared in dogs. s-Dobutamine increased VR by 49 +/- 10 ml, whereas NE increased VR by 14 +/- 6 ml during 5-min infusion. s-Dobutamine significantly increased coronary NBF in left ventricular (LV) endocardium from 115 +/- 10 to 194 +/- 13 and 263 +/- 9 ml/min/100 g at doses of 10 and 20 micrograms/kg/min, respectively. In addition, LV epicardium flow was increased from 87 +/- 8 to 189 +/- 15 and 262 +/- 11 ml/min/100 g at 10 and 20 micrograms/kg/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of S-dobutamine on venous blood return and organ nutrient blood flow. The selective contractile effects of s-dobutamine were studied in vitro in selected canine arteries and vein preparations; propranolol was included to block potential beta-mediated vasodilation. These in vitro data were expanded by quantifying the in vivo effects of s-dobutamine on venous blood return and redistribution of regional nutrient blood flow (NBF) and non-nutrient blood flow (non-NBF) in anesthetized dogs. In in vitro studies with isolated canine arteries and veins, s-dobutamine exhibited vein-selective constriction. At maximally efficacious concentrations of agonist, contractions of carotid, coronary, and femoral arteries in response to s-dobutamine were only 7, 25 and 45% as great as those elicited by norepinephrine (NE). Similarly, in jugular vein, s-dobutamine-mediated contractions were 55% as great as those obtained in response to NE. Coronary and femoral arteries precontracted with NE were relaxed in a dose-related manner by increasing concentrations of s-dobutamine. Effects of NE and s-dobutamine on venous blood return (VR) were compared in dogs. s-Dobutamine increased VR by 49 +/- 10 ml, whereas NE increased VR by 14 +/- 6 ml during 5-min infusion. s-Dobutamine significantly increased coronary NBF in left ventricular (LV) endocardium from 115 +/- 10 to 194 +/- 13 and 263 +/- 9 ml/min/100 g at doses of 10 and 20 micrograms/kg/min, respectively. In addition, LV epicardium flow was increased from 87 +/- 8 to 189 +/- 15 and 262 +/- 11 ml/min/100 g at 10 and 20 micrograms/kg/min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280737", "title": "Quality of life perception during antihypertensive treatment: a comparative study of bisoprolol and enalapril.", "content": "The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. We compared the effect on quality of life of the angiotensin-converting enzyme (ACE) inhibitor enalapril to the effect of bisoprolol as a representative of a new class of selective beta 1-adrenoreceptor blocking agents. Fifty-seven patients with mild to moderate hypertension were eligible to enter an 18-week cross-over study, consisting of a single-blind 2-week run-in period and two 8-week double-blind cross-over periods. At the end of the run-in period and the two cross-over periods, both systolic and diastolic blood pressure (SBP, DBP) were assessed, as was quality of life perception by the Inventory of Subjective Health. During bisoprolol treatment, supine BP decreased from 163 +/- 2/102 +/- 1 to 144 +/- 3/86 +/- 1 mm Hg. The antihypertensive effect was at least as good with bisoprolol as with enalapril. Quality of life perception as measured with the Inventory of Subjective Health was comparable for the two drugs. Spontaneously mentioned adverse effects were more frequent (74%) during enalapril than during bisoprolol treatment. At the end of the study, 69% of patients chose to continue antihypertensive treatment with bisoprolol. Our results show that the highly selective beta 1-adrenoreceptor blocking drug bisoprolol is at least as effective as enalapril and has no deleterious effects on well-being.", "contents": "Quality of life perception during antihypertensive treatment: a comparative study of bisoprolol and enalapril. The well-being of hypertensive patients may be adversely affected by the disease itself, its complications, and other concomitant processes such as anxiety, sedation, and side effects of prescribed drugs. Some recently developed antihypertensive agents have been suggested to be devoid of these deleterious effects on well-being expressed as quality of life. We compared the effect on quality of life of the angiotensin-converting enzyme (ACE) inhibitor enalapril to the effect of bisoprolol as a representative of a new class of selective beta 1-adrenoreceptor blocking agents. Fifty-seven patients with mild to moderate hypertension were eligible to enter an 18-week cross-over study, consisting of a single-blind 2-week run-in period and two 8-week double-blind cross-over periods. At the end of the run-in period and the two cross-over periods, both systolic and diastolic blood pressure (SBP, DBP) were assessed, as was quality of life perception by the Inventory of Subjective Health. During bisoprolol treatment, supine BP decreased from 163 +/- 2/102 +/- 1 to 144 +/- 3/86 +/- 1 mm Hg. The antihypertensive effect was at least as good with bisoprolol as with enalapril. Quality of life perception as measured with the Inventory of Subjective Health was comparable for the two drugs. Spontaneously mentioned adverse effects were more frequent (74%) during enalapril than during bisoprolol treatment. At the end of the study, 69% of patients chose to continue antihypertensive treatment with bisoprolol. Our results show that the highly selective beta 1-adrenoreceptor blocking drug bisoprolol is at least as effective as enalapril and has no deleterious effects on well-being."} {"id": "PMID:1280738", "title": "Cardiovascular effects of omega-conopeptides in conscious rats: mechanisms of action.", "content": "We examined the effects of omega-conopeptides, a novel class of neuronal voltage-gated calcium channel antagonists, on hemodynamic responses in rats. Intravenous (i.v.) injections of SNX-111 (omega-conopeptide MVIIA) dose-dependently decreased arterial blood pressure (BP) in conscious rats. Intracerebroventricular (i.c.v.) SNX-111 injections (580 pmol) tended to increase BP and, after an initial decrease, to increase heart rate (HR). The dose-response curve for SNX-111 administered i.v. in conscious rats was biphasic. Beginning at subdepressor doses, SNX-111 caused a long-lasting blockade of pressor responses elicited by sympathetic nerve stimulation in pithed animals but did not prevent increases in BP evoked by exogenously administered norepinephrine (NE). Pretreatment of rats with histamine antagonists partially blocked the hypotensive effects of the higher (870 and 2,900 nmol/kg) doses of SNX-111. Substitution of alanine for arginine at position 10 ([Ala10]-MVIIA) markedly attenuated the histamine-mediated component of the vasodepressor response. Together, these findings indicate that SNX-111 administered i.v. decreases systemic BP by a combination of blockade of sympathetic neurotransmission and mast cell degranulation; the latter function appears to be dependent on the arginine residue in position 10 of the amino acid sequence of SNX-111.", "contents": "Cardiovascular effects of omega-conopeptides in conscious rats: mechanisms of action. We examined the effects of omega-conopeptides, a novel class of neuronal voltage-gated calcium channel antagonists, on hemodynamic responses in rats. Intravenous (i.v.) injections of SNX-111 (omega-conopeptide MVIIA) dose-dependently decreased arterial blood pressure (BP) in conscious rats. Intracerebroventricular (i.c.v.) SNX-111 injections (580 pmol) tended to increase BP and, after an initial decrease, to increase heart rate (HR). The dose-response curve for SNX-111 administered i.v. in conscious rats was biphasic. Beginning at subdepressor doses, SNX-111 caused a long-lasting blockade of pressor responses elicited by sympathetic nerve stimulation in pithed animals but did not prevent increases in BP evoked by exogenously administered norepinephrine (NE). Pretreatment of rats with histamine antagonists partially blocked the hypotensive effects of the higher (870 and 2,900 nmol/kg) doses of SNX-111. Substitution of alanine for arginine at position 10 ([Ala10]-MVIIA) markedly attenuated the histamine-mediated component of the vasodepressor response. Together, these findings indicate that SNX-111 administered i.v. decreases systemic BP by a combination of blockade of sympathetic neurotransmission and mast cell degranulation; the latter function appears to be dependent on the arginine residue in position 10 of the amino acid sequence of SNX-111."} {"id": "PMID:1280739", "title": "Nicorandil attenuates myocardial dysfunction associated with transient ischemia by opening ATP-dependent potassium channels.", "content": "The objective of this study was to determine whether ATP-dependent potassium channel activation is involved in the mechanism by which nicorandil reduces postischemic contractile dysfunction produced by a brief period of ischemia (myocardial stunning). Barbital-anesthetized dogs were subjected to 15-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. Saline or nicorandil (100 micrograms/kg + 25 micrograms/kg/min) were infused 15 min before and throughout occlusion with or without addition of the KATP channel antagonist, glibenclamide 0.3 mg/kg as an intravenous (i.v.) bolus. Regional myocardial blood flow was measured by radioactive microspheres, and left ventricular (LV) segment function was measured by sonomicrometry. There were no significant differences between the groups in area-at-risk size or collateral blood flow. In contrast, nicorandil significantly reduced mean aortic blood pressure (BP) and the rate-pressure product (RPP) which persisted throughout the occlusion period. In addition, nicorandil markedly accelerated recovery of segment shortening in the ischemic/reperfused region as compared with control dogs. Pretreatment of dogs with glibenclamide blocked none of the hemodynamic effects of nicorandil, but it did prevent improvement in reperfusion segment function. The small dose of glibenclamide used had no effect on hemodynamics or the degree of stunning. Thus, these results suggest that nicorandil attenuates stunning in anesthetized dogs by a direct cardioprotective effect as a result of KATP channel activation in ischemic myocardium.", "contents": "Nicorandil attenuates myocardial dysfunction associated with transient ischemia by opening ATP-dependent potassium channels. The objective of this study was to determine whether ATP-dependent potassium channel activation is involved in the mechanism by which nicorandil reduces postischemic contractile dysfunction produced by a brief period of ischemia (myocardial stunning). Barbital-anesthetized dogs were subjected to 15-min left anterior descending (LAD) coronary artery occlusion followed by 3-h reperfusion. Saline or nicorandil (100 micrograms/kg + 25 micrograms/kg/min) were infused 15 min before and throughout occlusion with or without addition of the KATP channel antagonist, glibenclamide 0.3 mg/kg as an intravenous (i.v.) bolus. Regional myocardial blood flow was measured by radioactive microspheres, and left ventricular (LV) segment function was measured by sonomicrometry. There were no significant differences between the groups in area-at-risk size or collateral blood flow. In contrast, nicorandil significantly reduced mean aortic blood pressure (BP) and the rate-pressure product (RPP) which persisted throughout the occlusion period. In addition, nicorandil markedly accelerated recovery of segment shortening in the ischemic/reperfused region as compared with control dogs. Pretreatment of dogs with glibenclamide blocked none of the hemodynamic effects of nicorandil, but it did prevent improvement in reperfusion segment function. The small dose of glibenclamide used had no effect on hemodynamics or the degree of stunning. Thus, these results suggest that nicorandil attenuates stunning in anesthetized dogs by a direct cardioprotective effect as a result of KATP channel activation in ischemic myocardium."} {"id": "PMID:1280740", "title": "Angiotensin II receptor blockade after myocardial infarction in rats: effects on hemodynamics, myocardial DNA synthesis, and interstitial collagen content.", "content": "Angiotensin-converting enzyme (ACE) inhibitors are widely used for treatment of heart failure after myocardial infarction (MI). The beneficial effects consist of a combination of hemodynamic effects and interference with cardiac structural alterations. These effects are believed to depend on inhibition of angiotensin II (AII) formation and thus diminished angiotensin receptor stimulation. We administered the angiotensin II-1 (AT-1) receptor antagonist losartan during and after completion of the repair phase of an MI to investigate involvement of the AT-1 receptor in the above described effects of captopril. MI reduced cardiac output (CO) (sham 94 +/- 4 ml/min, MI 78 +/- 5 ml/min) and maximal CO (sham 154 +/- 4, MI 107 +/- 5 ml/min, respectively). Losartan (15 mg/kg/day) resulted in a rightward shift of the AII pressor dose-response curve by a factor of 32-40. Neither CO nor COVL,max was affected by losartan treatment in either phase (late treatment CO = 78 +/- 5, COVL,max = 118 +/- 9 ml/min). Although early treatment with losartan reduced cardiac hypertrophy measured as heart weight, DNA synthesis was reduced only slightly. In contrast, collagen deposition was inhibited completely. The results suggest that the effects of captopril in rats after MI are not dependent on AT-1 receptor-mediated mechanisms.", "contents": "Angiotensin II receptor blockade after myocardial infarction in rats: effects on hemodynamics, myocardial DNA synthesis, and interstitial collagen content. Angiotensin-converting enzyme (ACE) inhibitors are widely used for treatment of heart failure after myocardial infarction (MI). The beneficial effects consist of a combination of hemodynamic effects and interference with cardiac structural alterations. These effects are believed to depend on inhibition of angiotensin II (AII) formation and thus diminished angiotensin receptor stimulation. We administered the angiotensin II-1 (AT-1) receptor antagonist losartan during and after completion of the repair phase of an MI to investigate involvement of the AT-1 receptor in the above described effects of captopril. MI reduced cardiac output (CO) (sham 94 +/- 4 ml/min, MI 78 +/- 5 ml/min) and maximal CO (sham 154 +/- 4, MI 107 +/- 5 ml/min, respectively). Losartan (15 mg/kg/day) resulted in a rightward shift of the AII pressor dose-response curve by a factor of 32-40. Neither CO nor COVL,max was affected by losartan treatment in either phase (late treatment CO = 78 +/- 5, COVL,max = 118 +/- 9 ml/min). Although early treatment with losartan reduced cardiac hypertrophy measured as heart weight, DNA synthesis was reduced only slightly. In contrast, collagen deposition was inhibited completely. The results suggest that the effects of captopril in rats after MI are not dependent on AT-1 receptor-mediated mechanisms."} {"id": "PMID:1280741", "title": "Serotonin-induced vasoconstriction in dog kidney.", "content": "Serotonin (5-HT 0.1 and 0.3 micrograms/kg) was injected as a bolus into the renal artery of anesthetized dogs. Renal blood flow (RBF) decreased initially after 5-HT injection and then increased. The 5-HT-induced decrease in RBF was potentiated during intrarenal infusion of a 5-HT1 and 5-HT2 antagonist methysergide at 3 micrograms/kg/min or of a 5-HT2 antagonist ketanserin (3-30 micrograms/kg/min), but methysergide at 30 micrograms/kg/min attenuated the decrease in RBF. The delayed increase in RBF was suppressed during ketanserin or methysergide infusion. In ketanserin-pretreated dogs, methysergide (3-30 micrograms/kg/min) dose-dependently suppressed the 5-HT-induced decrease in RBF. A 5-HT3 antagonist, ICS 205-930 (3-30 micrograms/kg/min), did not affect the 5-HT-induced RBF responses. A Ca2+ entry blocker CD-349 (30 and 100 ng/kg/min) and a Ca2+ release inhibitor TMB-8 (30 and 100 micrograms/kg/min) suppressed the 5-HT-induced decrease in RBF. These results suggest that 5-HT activates 5-HT1 receptors to induce vasoconstriction by mobilization of extracellular and intracellular Ca2+, but simultaneous activation of 5-HT2 receptors attenuates the vasoconstriction, probably by causing vasodilation in dog kidney.", "contents": "Serotonin-induced vasoconstriction in dog kidney. Serotonin (5-HT 0.1 and 0.3 micrograms/kg) was injected as a bolus into the renal artery of anesthetized dogs. Renal blood flow (RBF) decreased initially after 5-HT injection and then increased. The 5-HT-induced decrease in RBF was potentiated during intrarenal infusion of a 5-HT1 and 5-HT2 antagonist methysergide at 3 micrograms/kg/min or of a 5-HT2 antagonist ketanserin (3-30 micrograms/kg/min), but methysergide at 30 micrograms/kg/min attenuated the decrease in RBF. The delayed increase in RBF was suppressed during ketanserin or methysergide infusion. In ketanserin-pretreated dogs, methysergide (3-30 micrograms/kg/min) dose-dependently suppressed the 5-HT-induced decrease in RBF. A 5-HT3 antagonist, ICS 205-930 (3-30 micrograms/kg/min), did not affect the 5-HT-induced RBF responses. A Ca2+ entry blocker CD-349 (30 and 100 ng/kg/min) and a Ca2+ release inhibitor TMB-8 (30 and 100 micrograms/kg/min) suppressed the 5-HT-induced decrease in RBF. These results suggest that 5-HT activates 5-HT1 receptors to induce vasoconstriction by mobilization of extracellular and intracellular Ca2+, but simultaneous activation of 5-HT2 receptors attenuates the vasoconstriction, probably by causing vasodilation in dog kidney."} {"id": "PMID:1280742", "title": "Terbutaline-induced downregulation of beta 2-adrenoceptors without Gi-protein alterations in human lymphocytes.", "content": "Recent evidence suggests that agonist-induced desensitization of Gs protein-coupled beta-adrenoceptors is accompanied by sensitization of Gi protein-coupled receptors and/or an increase in Gi protein. To find out whether such \"cross-regulation\" between Gs protein- and Gi protein-coupled receptors can be also demonstrated in vivo in humans, we studied the effects of a 2 week treatment of eight male volunteers with the beta 2-adrenoceptor agonist terbutaline (3 x 5 mg/day) on beta 2-adrenoceptor density and Gi-protein content in lymphocytes and on alpha 2-adrenoceptor density (Gi-coupled receptors) in platelets. Terbutaline decreased the lymphocyte beta 2-adrenoceptor density by about 30%, but had no significant influence on lymphocyte Gi-protein levels (assessed by pertussis toxin-catalyzed [32P]ADP ribosylation) or on platelet alpha 2-adrenoceptor density. We conclude that circulating blood cells are not suitable to demonstrate in humans in vivo a \"cross-regulation\" between Gs- and Gi-coupled beta- and alpha-adrenoceptors.", "contents": "Terbutaline-induced downregulation of beta 2-adrenoceptors without Gi-protein alterations in human lymphocytes. Recent evidence suggests that agonist-induced desensitization of Gs protein-coupled beta-adrenoceptors is accompanied by sensitization of Gi protein-coupled receptors and/or an increase in Gi protein. To find out whether such \"cross-regulation\" between Gs protein- and Gi protein-coupled receptors can be also demonstrated in vivo in humans, we studied the effects of a 2 week treatment of eight male volunteers with the beta 2-adrenoceptor agonist terbutaline (3 x 5 mg/day) on beta 2-adrenoceptor density and Gi-protein content in lymphocytes and on alpha 2-adrenoceptor density (Gi-coupled receptors) in platelets. Terbutaline decreased the lymphocyte beta 2-adrenoceptor density by about 30%, but had no significant influence on lymphocyte Gi-protein levels (assessed by pertussis toxin-catalyzed [32P]ADP ribosylation) or on platelet alpha 2-adrenoceptor density. We conclude that circulating blood cells are not suitable to demonstrate in humans in vivo a \"cross-regulation\" between Gs- and Gi-coupled beta- and alpha-adrenoceptors."} {"id": "PMID:1280743", "title": "Modulation of antigen- and ischemia-induced effects by the platelet-activating factor antagonist WEB-2086 in isolated sensitized rat hearts.", "content": "The modulatory role of the platelet-activating factor (PAF) antagonist WEB-2086 (30 microM) on the response to antigen-induced (trinitrophenyl-haptenized ovalbumin) and global ischemia (30 and 60 min)-induced changes in the response to antigen was studied in isolated hearts from actively sensitized rats. In sensitized normoxic hearts, both antigen (0.8 mg) and PAF (100 pmol) induced a short-term increase followed by a long-term decrease in coronary flow (CF). The antigen- but not the PAF-evoked increase in CF was accompanied by a substantial release of histamine. WEB-2086 enhanced the vasodilator effect and abolished the vasoconstrictor effect of 100 pmol of PAF but neither modified the coronary vascular effects of antigen nor the antigen-induced histamine release. Ischemia for 60 min followed by 30 min of reperfusion increased the diastolic left ventricular pressure but a 30-min period of ischemia and reperfusion had no effect on baseline cardiac function. WEB-2086 had no effect on ischemia-induced changes in cardiac function. A 30-min period of global ischemia enhanced the antigen-induced decrease in CF and systolic left ventricular pressure (SLVP). A 60 min period, however, suppressed the antigen-induced effects on CF and SLVP as well as antigen-induced histamine release. WEB-2086 partly protected the heart against the enhanced antigen-induced decrease in CF and SLVP after a 30-min period of global ischemia but no modulatory role of WEB-2086 was observed after 60 min of global ischemia. Our conclusions are that (a) PAF is not involved in rat cardiac anaphylaxis since WEB-2086 was proven to be inactive; (b) cardiac ischemia and cardiac anaphylaxis have interrelated mechanism of action since ischemia changed the anaphylactic response, which indicates that coincidence of these two pathological events could influence the clinical outcome; and (c) PAF is possibly involved in rat cardiac ischemia since WEB-2086 partly protected the heart against the enhanced antigen-induced decrease in CF and SLVP after 30 min of ischemia and reperfusion.", "contents": "Modulation of antigen- and ischemia-induced effects by the platelet-activating factor antagonist WEB-2086 in isolated sensitized rat hearts. The modulatory role of the platelet-activating factor (PAF) antagonist WEB-2086 (30 microM) on the response to antigen-induced (trinitrophenyl-haptenized ovalbumin) and global ischemia (30 and 60 min)-induced changes in the response to antigen was studied in isolated hearts from actively sensitized rats. In sensitized normoxic hearts, both antigen (0.8 mg) and PAF (100 pmol) induced a short-term increase followed by a long-term decrease in coronary flow (CF). The antigen- but not the PAF-evoked increase in CF was accompanied by a substantial release of histamine. WEB-2086 enhanced the vasodilator effect and abolished the vasoconstrictor effect of 100 pmol of PAF but neither modified the coronary vascular effects of antigen nor the antigen-induced histamine release. Ischemia for 60 min followed by 30 min of reperfusion increased the diastolic left ventricular pressure but a 30-min period of ischemia and reperfusion had no effect on baseline cardiac function. WEB-2086 had no effect on ischemia-induced changes in cardiac function. A 30-min period of global ischemia enhanced the antigen-induced decrease in CF and systolic left ventricular pressure (SLVP). A 60 min period, however, suppressed the antigen-induced effects on CF and SLVP as well as antigen-induced histamine release. WEB-2086 partly protected the heart against the enhanced antigen-induced decrease in CF and SLVP after a 30-min period of global ischemia but no modulatory role of WEB-2086 was observed after 60 min of global ischemia. Our conclusions are that (a) PAF is not involved in rat cardiac anaphylaxis since WEB-2086 was proven to be inactive; (b) cardiac ischemia and cardiac anaphylaxis have interrelated mechanism of action since ischemia changed the anaphylactic response, which indicates that coincidence of these two pathological events could influence the clinical outcome; and (c) PAF is possibly involved in rat cardiac ischemia since WEB-2086 partly protected the heart against the enhanced antigen-induced decrease in CF and SLVP after 30 min of ischemia and reperfusion."} {"id": "PMID:1280744", "title": "Effect of therapeutic dopamine administration on myocardial catecholamine and neuropeptide Y concentrations in the failing ventricles of patients with idiopathic dilated cardiomyopathy.", "content": "The purpose of this study was to investigate the relationship between dopamine (DA) exposure and myocardial catecholamine and neuropeptide Y (NPY) concentrations in patients with severe congestive heart failure due to idiopathic dilated cardiomyopathy (IDC). Both nonfailing (NF) and failing (F) hearts were obtained in collaboration with the Utah Cardiac Transplantation Program and the Intermountain Organ Recovery System. The patients were stratified into five groups according to their preoperative exposure to dobutamine (DBT) and/or DA. Compared to 12 untreated, NF control hearts, norepinephrine (NE) concentrations were significantly decreased in 30 untreated F hearts obtained from patients with IDC. Norepinephrine concentrations were also significantly decreased in DA-treated NF hearts and in DA-treated F hearts compared to untreated NF and untreated or DBT-treated failing hearts, respectively. NPY concentrations were significantly decreased in untreated F hearts and were further decreased in dopamine-treated NF and DA-treated F hearts compared to untreated NF and untreated or DBT-treated F hearts. Thus, NE and NPY depletion related to DA administration was evident in both NF and F myocardium and was specific for DA in that it was not evident in patients who received the direct-acting beta-agonist inotrope DBT. These data suggest that the major inotropic mechanism of action of DA is through cardiac adrenergic neurotransmitter release. The data also provide further support for the concept that indirect acting inotropes such as DA may have limited inotropic potential in F hearts where neuronal NE has been depleted.", "contents": "Effect of therapeutic dopamine administration on myocardial catecholamine and neuropeptide Y concentrations in the failing ventricles of patients with idiopathic dilated cardiomyopathy. The purpose of this study was to investigate the relationship between dopamine (DA) exposure and myocardial catecholamine and neuropeptide Y (NPY) concentrations in patients with severe congestive heart failure due to idiopathic dilated cardiomyopathy (IDC). Both nonfailing (NF) and failing (F) hearts were obtained in collaboration with the Utah Cardiac Transplantation Program and the Intermountain Organ Recovery System. The patients were stratified into five groups according to their preoperative exposure to dobutamine (DBT) and/or DA. Compared to 12 untreated, NF control hearts, norepinephrine (NE) concentrations were significantly decreased in 30 untreated F hearts obtained from patients with IDC. Norepinephrine concentrations were also significantly decreased in DA-treated NF hearts and in DA-treated F hearts compared to untreated NF and untreated or DBT-treated failing hearts, respectively. NPY concentrations were significantly decreased in untreated F hearts and were further decreased in dopamine-treated NF and DA-treated F hearts compared to untreated NF and untreated or DBT-treated F hearts. Thus, NE and NPY depletion related to DA administration was evident in both NF and F myocardium and was specific for DA in that it was not evident in patients who received the direct-acting beta-agonist inotrope DBT. These data suggest that the major inotropic mechanism of action of DA is through cardiac adrenergic neurotransmitter release. The data also provide further support for the concept that indirect acting inotropes such as DA may have limited inotropic potential in F hearts where neuronal NE has been depleted."} {"id": "PMID:1280745", "title": "C14-aminosteroid LNF 209, an agent with positive inotropic and antimuscarinic activity.", "content": "LNF 209 is a cardioactive steroid containing at position C14 a protonized amino group. It was tested whether LNF 209 has antimuscarinic properties besides its cardiotonic effect, which was also quantified. In guinea pig left atria (3 Hz, 0.9 mM Ca2+, 5.4 mM K+), LNF 209 increased the force of contraction at concentrations > or = 1 microM, thus having a tenfold lower potency than ouabain. Correspondingly, cardiac glycoside binding sites in guinea pig cardiac membranes labeled with [3H]ouabain were occupied by LNF 209 (Ki = 1.7 microM) at concentrations tenfold higher compared with ouabain (Kd = 0.14 microM). The negative inotropic effect of the muscarinic agonist oxotremorine was antagonized by LNF 209, but not by ouabain; in the Schild plot, the data for LNF 209 could be connected by a line with a slope of unity and a pA2 = 7.5. The binding of [3H]N-methylscopolamine ([3H]NMS) to the M2-cholinoceptors in guinea pig cardiac membranes was inhibited by LNF 209 with a Ki = 0.5 microM; LNF reduced the affinity of [3H]NMS binding without affecting the number of receptor sites. In isolated segments of guinea pig ileum, LNF 209 antagonized the effect of oxotremorine with a pA2 = 7.4. It is concluded that LNF 209 is a competitive antagonist at M-cholinoceptors without preference for the cardiac M2-cholinoceptors. Whether the antimuscarinic property is of significance in species highly sensitive to digitalis remains to be established.", "contents": "C14-aminosteroid LNF 209, an agent with positive inotropic and antimuscarinic activity. LNF 209 is a cardioactive steroid containing at position C14 a protonized amino group. It was tested whether LNF 209 has antimuscarinic properties besides its cardiotonic effect, which was also quantified. In guinea pig left atria (3 Hz, 0.9 mM Ca2+, 5.4 mM K+), LNF 209 increased the force of contraction at concentrations > or = 1 microM, thus having a tenfold lower potency than ouabain. Correspondingly, cardiac glycoside binding sites in guinea pig cardiac membranes labeled with [3H]ouabain were occupied by LNF 209 (Ki = 1.7 microM) at concentrations tenfold higher compared with ouabain (Kd = 0.14 microM). The negative inotropic effect of the muscarinic agonist oxotremorine was antagonized by LNF 209, but not by ouabain; in the Schild plot, the data for LNF 209 could be connected by a line with a slope of unity and a pA2 = 7.5. The binding of [3H]N-methylscopolamine ([3H]NMS) to the M2-cholinoceptors in guinea pig cardiac membranes was inhibited by LNF 209 with a Ki = 0.5 microM; LNF reduced the affinity of [3H]NMS binding without affecting the number of receptor sites. In isolated segments of guinea pig ileum, LNF 209 antagonized the effect of oxotremorine with a pA2 = 7.4. It is concluded that LNF 209 is a competitive antagonist at M-cholinoceptors without preference for the cardiac M2-cholinoceptors. Whether the antimuscarinic property is of significance in species highly sensitive to digitalis remains to be established."} {"id": "PMID:1280746", "title": "Tumour necrosis factor alpha augments the release of an endothelium-dependent vasoconstrictor from human polymorphonuclear leukocytes.", "content": "We have studied the effect of cytokine priming by recombinant human tumour necrosis factor alpha (rhTNF alpha) on the release of vasoactive mediators from human polymorphonuclear leukocytes (PMNs). Supernatants of human PMNs (100 microliters, 5 x 10(7) ml, from 12 donors) relaxed precontracted rabbit aortic rings. The relaxations were preceded by a transient contraction in four experiments. In contrast, supernatants of PMNs incubated with rhTNF alpha (0.3 nM, 30 min, 37 degrees C) elicited variable vascular responses that consisted of either a sustained contraction (n = 4), a transient contraction followed by a sustained relaxation (n = 2), or a sustained relaxation only (n = 6). The vascular tone produced by the rhTNF alpha-treated PMN supernatant was significantly greater over 30 min than that produced by the control supernatant (p < 0.01). Endothelium removal prevented the PMN-induced contractions and significantly decreased the vascular tone produced by all rhTNF alpha-treated PMN supernatants (p < 0.05). The PMN supernatants had no vasoactive effect on aortic rings at resting tension. Molecular size analysis indicated that the PMN-derived contractile mediator is > 30,000 Da. These results suggest that human PMNs, primed by rhTNF alpha, release a stable endothelium-dependent vasoconstrictor that opposes the action of a stable, spontaneously released direct vasodilator.", "contents": "Tumour necrosis factor alpha augments the release of an endothelium-dependent vasoconstrictor from human polymorphonuclear leukocytes. We have studied the effect of cytokine priming by recombinant human tumour necrosis factor alpha (rhTNF alpha) on the release of vasoactive mediators from human polymorphonuclear leukocytes (PMNs). Supernatants of human PMNs (100 microliters, 5 x 10(7) ml, from 12 donors) relaxed precontracted rabbit aortic rings. The relaxations were preceded by a transient contraction in four experiments. In contrast, supernatants of PMNs incubated with rhTNF alpha (0.3 nM, 30 min, 37 degrees C) elicited variable vascular responses that consisted of either a sustained contraction (n = 4), a transient contraction followed by a sustained relaxation (n = 2), or a sustained relaxation only (n = 6). The vascular tone produced by the rhTNF alpha-treated PMN supernatant was significantly greater over 30 min than that produced by the control supernatant (p < 0.01). Endothelium removal prevented the PMN-induced contractions and significantly decreased the vascular tone produced by all rhTNF alpha-treated PMN supernatants (p < 0.05). The PMN supernatants had no vasoactive effect on aortic rings at resting tension. Molecular size analysis indicated that the PMN-derived contractile mediator is > 30,000 Da. These results suggest that human PMNs, primed by rhTNF alpha, release a stable endothelium-dependent vasoconstrictor that opposes the action of a stable, spontaneously released direct vasodilator."} {"id": "PMID:1280747", "title": "Enalapril increases cardiac refractoriness.", "content": "The influence of enalapril--an angiotensin converting enzyme inhibitor--on cardiac refractoriness was investigated. Strength-interval curves were initially obtained under control conditions and after exposing the muscles to Tyrode solution containing 50 micrograms/ml of enalapril. The results indicate that enalapril displaced the strength-curves to the right. The minimal current intensity required to elicit a propagated response was clearly increased by enalapril at all the intervals used. No change in action potential duration was found with enalapril but the action potential amplitude and the resting potential were both increased. The rise in cardiac refractoriness caused by enalapril might indicate that the drug has anti-arrhythmic properties.", "contents": "Enalapril increases cardiac refractoriness. The influence of enalapril--an angiotensin converting enzyme inhibitor--on cardiac refractoriness was investigated. Strength-interval curves were initially obtained under control conditions and after exposing the muscles to Tyrode solution containing 50 micrograms/ml of enalapril. The results indicate that enalapril displaced the strength-curves to the right. The minimal current intensity required to elicit a propagated response was clearly increased by enalapril at all the intervals used. No change in action potential duration was found with enalapril but the action potential amplitude and the resting potential were both increased. The rise in cardiac refractoriness caused by enalapril might indicate that the drug has anti-arrhythmic properties."} {"id": "PMID:1280748", "title": "Central noradrenergic activity and the cardiovascular effects of nitroglycerin and amyl nitrate.", "content": "Intracerebroventricular and i.v. administration of nitroglycerin in anesthetized Sprague-Dawley rats produced dose-dependent decreases in mean arterial pressure and increases in heart rate, but intracisternal injection of the drug induced hypotension and bradycardia. Hypotensive responses to intracisternal injection of nitroglycerin showed that the compound was two to three times more potent than by i.v. administration (six times when comparing the area under the curve). Intravenous sodium nitroprusside produced dose-dependent hypotensive and tachycardiac effects, but minimal responses were induced by i.c.v. and intracisternal injection. Central pretreatment with either yohimbine or rauwolscine antagonized hypotensive responses to i.c.v. and i.v. nitroglycerin, but did not alter the depressor responses induced by i.v. sodium nitroprusside. Tachycardiac responses to i.c.v. nitroglycerin are greater than the responses induced by i.v. administration. Inhalation of amyl nitrite produced marked hypotensive responses, with the dose-response curves being shifted to the right by i.c.v. pretreatment with rauwolscine, but not by i.v. pretreatment. The concentrations of 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol in cerebrospinal fluid were increased by i.v., i.c.v., and intracisternal administration of nitroglycerin, but were not altered by i.v. sodium nitroprusside. The concentrations of dihydroxyphenylacetic acid were elevated by i.v. and i.c.v. injection of nitroglycerin. Results suggest that nitroglycerin stimulates central noradrenergic activity, which may be involved in the component of hypotensive effects of the drug. Reflex tachycardiac responses to nitroglycerin may be further complicated by forebrain stimulation and medulla-mediated bradycardia. Sodium nitroprusside did not demonstrate central activity.", "contents": "Central noradrenergic activity and the cardiovascular effects of nitroglycerin and amyl nitrate. Intracerebroventricular and i.v. administration of nitroglycerin in anesthetized Sprague-Dawley rats produced dose-dependent decreases in mean arterial pressure and increases in heart rate, but intracisternal injection of the drug induced hypotension and bradycardia. Hypotensive responses to intracisternal injection of nitroglycerin showed that the compound was two to three times more potent than by i.v. administration (six times when comparing the area under the curve). Intravenous sodium nitroprusside produced dose-dependent hypotensive and tachycardiac effects, but minimal responses were induced by i.c.v. and intracisternal injection. Central pretreatment with either yohimbine or rauwolscine antagonized hypotensive responses to i.c.v. and i.v. nitroglycerin, but did not alter the depressor responses induced by i.v. sodium nitroprusside. Tachycardiac responses to i.c.v. nitroglycerin are greater than the responses induced by i.v. administration. Inhalation of amyl nitrite produced marked hypotensive responses, with the dose-response curves being shifted to the right by i.c.v. pretreatment with rauwolscine, but not by i.v. pretreatment. The concentrations of 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol in cerebrospinal fluid were increased by i.v., i.c.v., and intracisternal administration of nitroglycerin, but were not altered by i.v. sodium nitroprusside. The concentrations of dihydroxyphenylacetic acid were elevated by i.v. and i.c.v. injection of nitroglycerin. Results suggest that nitroglycerin stimulates central noradrenergic activity, which may be involved in the component of hypotensive effects of the drug. Reflex tachycardiac responses to nitroglycerin may be further complicated by forebrain stimulation and medulla-mediated bradycardia. Sodium nitroprusside did not demonstrate central activity."} {"id": "PMID:1280749", "title": "Absence of hemodynamic deterioration in the presence of amlodipine following experimental myocardial infarction.", "content": "In general, calcium channel blockers have not been used in patients during acute myocardial infarction as they may exacerbate heart failure, possibly by neuro-humoral stimulation. Amlodipine, a new dihydropyridine calcium channel blocker without neurohumoral stimulation, was tested in an experimental model of acute myocardial infarction with assessment of hemodynamics, left ventricular (LV) function, and infarct size. Anesthetized dogs were subjected to 3 h of coronary artery occlusion followed by 3 h of reperfusion. At 2 h of occlusion, they were randomized to receive either amlodipine (250 micrograms/kg, n = 11) or saline (n = 11). Before treatment, all variables were similar in both groups. The diastolic pressure was unchanged following saline, but was reduced following amlodipine by 1 h after therapy (from 94 +/- 5 to 71 +/- 3 mm Hg, p < 0.0001 vs. saline) and for the duration of the protocol. Indices of left ventricular (LV) function did not deteriorate with amlodipine treatment compared with saline. After 3 h of reperfusion, the LV dP/dt was 1,720 +/- 114 mm Hg/s in the saline group and 1,958 +/- 167 mm Hg/s with amlodipine (p = ns). The area ejection fraction, assessed by echocardiography, was similar in both groups (43 +/- 5%, saline; 45 +/- 3%, amlodipine; p = ns), as was the LV end-diastolic pressure (8 +/- 1 mm Hg, saline; 7 +/- 1 mm Hg, amlodipine; p = ns). Subendocardial regional myocardial blood flow, measured by radioactive microspheres, was 0.75 +/- 0.08 ml/min/g with saline and 1.34 +/- 0.33 ml/min/g with amlodipine in the previously ischemic reperfused subendocardium (p = 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Absence of hemodynamic deterioration in the presence of amlodipine following experimental myocardial infarction. In general, calcium channel blockers have not been used in patients during acute myocardial infarction as they may exacerbate heart failure, possibly by neuro-humoral stimulation. Amlodipine, a new dihydropyridine calcium channel blocker without neurohumoral stimulation, was tested in an experimental model of acute myocardial infarction with assessment of hemodynamics, left ventricular (LV) function, and infarct size. Anesthetized dogs were subjected to 3 h of coronary artery occlusion followed by 3 h of reperfusion. At 2 h of occlusion, they were randomized to receive either amlodipine (250 micrograms/kg, n = 11) or saline (n = 11). Before treatment, all variables were similar in both groups. The diastolic pressure was unchanged following saline, but was reduced following amlodipine by 1 h after therapy (from 94 +/- 5 to 71 +/- 3 mm Hg, p < 0.0001 vs. saline) and for the duration of the protocol. Indices of left ventricular (LV) function did not deteriorate with amlodipine treatment compared with saline. After 3 h of reperfusion, the LV dP/dt was 1,720 +/- 114 mm Hg/s in the saline group and 1,958 +/- 167 mm Hg/s with amlodipine (p = ns). The area ejection fraction, assessed by echocardiography, was similar in both groups (43 +/- 5%, saline; 45 +/- 3%, amlodipine; p = ns), as was the LV end-diastolic pressure (8 +/- 1 mm Hg, saline; 7 +/- 1 mm Hg, amlodipine; p = ns). Subendocardial regional myocardial blood flow, measured by radioactive microspheres, was 0.75 +/- 0.08 ml/min/g with saline and 1.34 +/- 0.33 ml/min/g with amlodipine in the previously ischemic reperfused subendocardium (p = 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280750", "title": "The effect of transforming growth factor-alpha on airway angiogenesis.", "content": "A problem in lung transplantation is tracheal or bronchial dehiscence from ischemia. To determine if an angiogenic factor applied to the airway would improve capillary regrowth, a three-ring segment of trachea was completely severed and sutured in rats. In one group of animals the ischemic segment was wrapped with Gelfoam soaked in an angiogenic factor, transforming growth factor-alpha. In a second group the ischemic area was wrapped with Gelfoam soaked with only the vehicle. In a third group the devascularized area received no additional treatment. One animal from each group was killed daily for 7 days after operation. The tracheal vasculature was cast and viewed by light and scanning electron microscopy. None of the four animals that died early were in the transforming growth factor-alpha group. All animals lost weight between the day of operation and death, but this was least in the transforming growth factor-alpha group (p = 0.05). The light microscopy showed ischemic changes and the development of granulation tissue. The scanning electron microscopy of the vascular casts showed extensive loss of the vessels in the cut area. On day 1 the vessels of all animals dilated and their walls became rough. By day 3 a few corkscrew vessels penetrated the ischemic zone. By day 4 the animal that received transforming growth factor-alpha had more capillaries than the others. By day 6 revascularization in the transforming growth factor-alpha animal was abundant. Besides budding, new capillaries appeared to develop by lateral growth. After the fifth day vessels about 30 to 50 microns in diameter bulged focally. On the bulges, ridges the size, shape, and pattern of capillaries formed. Capillary formation in this manner has not been reported previously. Revascularization emerged sooner and more extensively with transforming growth factor-alpha. No adverse effect of transforming growth factor-alpha was found.", "contents": "The effect of transforming growth factor-alpha on airway angiogenesis. A problem in lung transplantation is tracheal or bronchial dehiscence from ischemia. To determine if an angiogenic factor applied to the airway would improve capillary regrowth, a three-ring segment of trachea was completely severed and sutured in rats. In one group of animals the ischemic segment was wrapped with Gelfoam soaked in an angiogenic factor, transforming growth factor-alpha. In a second group the ischemic area was wrapped with Gelfoam soaked with only the vehicle. In a third group the devascularized area received no additional treatment. One animal from each group was killed daily for 7 days after operation. The tracheal vasculature was cast and viewed by light and scanning electron microscopy. None of the four animals that died early were in the transforming growth factor-alpha group. All animals lost weight between the day of operation and death, but this was least in the transforming growth factor-alpha group (p = 0.05). The light microscopy showed ischemic changes and the development of granulation tissue. The scanning electron microscopy of the vascular casts showed extensive loss of the vessels in the cut area. On day 1 the vessels of all animals dilated and their walls became rough. By day 3 a few corkscrew vessels penetrated the ischemic zone. By day 4 the animal that received transforming growth factor-alpha had more capillaries than the others. By day 6 revascularization in the transforming growth factor-alpha animal was abundant. Besides budding, new capillaries appeared to develop by lateral growth. After the fifth day vessels about 30 to 50 microns in diameter bulged focally. On the bulges, ridges the size, shape, and pattern of capillaries formed. Capillary formation in this manner has not been reported previously. Revascularization emerged sooner and more extensively with transforming growth factor-alpha. No adverse effect of transforming growth factor-alpha was found."} {"id": "PMID:1280751", "title": "Measurement of serum cytokine levels in patients with myelodysplastic syndromes.", "content": "Sera of 25 healthy controls and 75 patients suffering from myelodysplastic syndromes (MDS) were investigated for serum concentration of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), erythropoietin (Epo), and tumor necrosis factor-alpha (TNF-alpha). According to French-American-British (FAB) classification, 21 refractory anemia (RA), seven refractory anemia with ring sideroblasts (RARS), 15 chronic myelomonocytic leukemia (CMML), 12 refractory anemia with excess of blasts (RAEB), and 20 RAEB in transformation (RAEBt) were examined. TNF-alpha levels were inversely correlated with lower levels of hemoglobin concentration (r = -0.31, p = 0.005), irrespective of the requirements for transfusion in anemic MDS patients. Significant differences in TNF-alpha levels between CMML (26.2 +/- 5.9 pg/ml) and the FAB subgroups (16.1 +/- 1.6 pg/ml) were detected. There was an overall inverse relationship between the level of erythropoietin and the degree of anemia, but a wide range of Epo response between patients with similar hemoglobin concentrations. Serum levels of IL-1 alpha and GM-CSF were undetected in most of the patients. In 57% of the samples there were detectable levels of G-CSF, without a correlation of the serum levels with blood cell counts, nor with any of the FAB subcategories. Overall, 29% and 25% of the patient sera exhibited elevated IL-3 and IL-6 levels, respectively. There was no correlation of the serum levels with any of the blood counts, other cytokines, nor FAB subcategories. In conclusion, simple negative feedback mechanism between a specific cytokine and the production of blood cells seems not to be the case in MDS, except for red cell production and erythropoietin concentration. Our data may suggest the involvement of TNF-alpha in the pathogenesis of anemia in MDS.", "contents": "Measurement of serum cytokine levels in patients with myelodysplastic syndromes. Sera of 25 healthy controls and 75 patients suffering from myelodysplastic syndromes (MDS) were investigated for serum concentration of interleukin-1 alpha (IL-1 alpha), IL-3, IL-6, granulocyte-colony-stimulating factor (G-CSF), granulocyte-macrophage-CSF (GM-CSF), erythropoietin (Epo), and tumor necrosis factor-alpha (TNF-alpha). According to French-American-British (FAB) classification, 21 refractory anemia (RA), seven refractory anemia with ring sideroblasts (RARS), 15 chronic myelomonocytic leukemia (CMML), 12 refractory anemia with excess of blasts (RAEB), and 20 RAEB in transformation (RAEBt) were examined. TNF-alpha levels were inversely correlated with lower levels of hemoglobin concentration (r = -0.31, p = 0.005), irrespective of the requirements for transfusion in anemic MDS patients. Significant differences in TNF-alpha levels between CMML (26.2 +/- 5.9 pg/ml) and the FAB subgroups (16.1 +/- 1.6 pg/ml) were detected. There was an overall inverse relationship between the level of erythropoietin and the degree of anemia, but a wide range of Epo response between patients with similar hemoglobin concentrations. Serum levels of IL-1 alpha and GM-CSF were undetected in most of the patients. In 57% of the samples there were detectable levels of G-CSF, without a correlation of the serum levels with blood cell counts, nor with any of the FAB subcategories. Overall, 29% and 25% of the patient sera exhibited elevated IL-3 and IL-6 levels, respectively. There was no correlation of the serum levels with any of the blood counts, other cytokines, nor FAB subcategories. In conclusion, simple negative feedback mechanism between a specific cytokine and the production of blood cells seems not to be the case in MDS, except for red cell production and erythropoietin concentration. Our data may suggest the involvement of TNF-alpha in the pathogenesis of anemia in MDS."} {"id": "PMID:1280752", "title": "Utility of immediate on-site cytopathological procurement and evaluation in fine needle aspiration biopsy of head and neck masses.", "content": "The utility of on-site microscopic evaluation of fine needle aspirates (FNAs) of the head and neck was assessed by comparing the diagnostic yield in 336 specimens obtained with immediate on-site cytopathological procurement and evaluation to that achieved in 548 cases performed without immediate on-site evaluation. Three hundred six (91%) of 336 immediate evaluation specimens were adequate for cytopathologic diagnosis, compared to 391 (71%) of 548 specimens not evaluated immediately (P < .001, chi-squared test). The higher satisfactory rate in immediate evaluation cases was related primarily to 1. immediate reaspiration of the masses until sufficient cytopathologic material was obtained for diagnosis; and 2. optimal specimen preparation. It is concluded that immediate on-site cytopathological procurement and evaluation of fine needle aspirates of head and neck masses is a valuable practice which assures a higher yield of adequate specimens compared to biopsies taken without immediate evaluation. The technique of immediate on-site evaluation of FNAs is discussed and a cost-benefit analysis of immediate on-site evaluation of FNAs is presented.", "contents": "Utility of immediate on-site cytopathological procurement and evaluation in fine needle aspiration biopsy of head and neck masses. The utility of on-site microscopic evaluation of fine needle aspirates (FNAs) of the head and neck was assessed by comparing the diagnostic yield in 336 specimens obtained with immediate on-site cytopathological procurement and evaluation to that achieved in 548 cases performed without immediate on-site evaluation. Three hundred six (91%) of 336 immediate evaluation specimens were adequate for cytopathologic diagnosis, compared to 391 (71%) of 548 specimens not evaluated immediately (P < .001, chi-squared test). The higher satisfactory rate in immediate evaluation cases was related primarily to 1. immediate reaspiration of the masses until sufficient cytopathologic material was obtained for diagnosis; and 2. optimal specimen preparation. It is concluded that immediate on-site cytopathological procurement and evaluation of fine needle aspirates of head and neck masses is a valuable practice which assures a higher yield of adequate specimens compared to biopsies taken without immediate evaluation. The technique of immediate on-site evaluation of FNAs is discussed and a cost-benefit analysis of immediate on-site evaluation of FNAs is presented."} {"id": "PMID:1280753", "title": "Laser-induced hyperthermia: comparison of two different methods.", "content": "The effectiveness of two different techniques of laser-induced hyperthermia was analyzed in healthy piglet livers. Hyperthermia was produced using a continuous-wave Nd:YAG laser with both a contact sapphire probe and a bare quartz fibre. In both methods the tip was inserted into the liver, and the temperature 1 cm from the tip was raised and held between 42 degrees C and 44 degrees C for 600 seconds. Specimens were taken 0, 7 and 14 days after the treatment. The tissue effects of 36 treatment sites were analysed using standard van Gieson's method. In addition, a histochemical method for demonstrating lactate dehydrogenase activity was employed to show damage not observable by routine methods. No statistically significant difference in the extent of the treatment sites at d 0 and after 7 days was seen when comparing the two laser methods. After 2 weeks, the diameter of the lesion with the bare fibre was significantly larger (3,7 mm with both analysing methods) than by using the contact probe (2,6 with LDH demonstration; P < 0.01 and 2.1 mm with van Gieson's staining; P < 0.001). It can be concluded that the simple fibre tip seems more effective in causing tissue necrosis than the sapphire tip.", "contents": "Laser-induced hyperthermia: comparison of two different methods. The effectiveness of two different techniques of laser-induced hyperthermia was analyzed in healthy piglet livers. Hyperthermia was produced using a continuous-wave Nd:YAG laser with both a contact sapphire probe and a bare quartz fibre. In both methods the tip was inserted into the liver, and the temperature 1 cm from the tip was raised and held between 42 degrees C and 44 degrees C for 600 seconds. Specimens were taken 0, 7 and 14 days after the treatment. The tissue effects of 36 treatment sites were analysed using standard van Gieson's method. In addition, a histochemical method for demonstrating lactate dehydrogenase activity was employed to show damage not observable by routine methods. No statistically significant difference in the extent of the treatment sites at d 0 and after 7 days was seen when comparing the two laser methods. After 2 weeks, the diameter of the lesion with the bare fibre was significantly larger (3,7 mm with both analysing methods) than by using the contact probe (2,6 with LDH demonstration; P < 0.01 and 2.1 mm with van Gieson's staining; P < 0.001). It can be concluded that the simple fibre tip seems more effective in causing tissue necrosis than the sapphire tip."} {"id": "PMID:1280754", "title": "Possible involvement of nitric oxide in chlordiazepoxide-induced anxiolysis in mice.", "content": "Mice challenged with the anxiolytic benzodiazepine chlordiazepoxide exhibited significant increases in the percent of total entries into and percent of total time spent on open arms of an elevated plus maze. Systemic pretreatment with the nitric oxide synthase-inhibitor L-NG-nitro arginine (L-NOARG) antagonized these effects of chlordiazepoxide. This inhibitory effect of L-NOARG was stereospecifically and completely reversed by intracerebroventricular administration of L-arginine but not D-arginine. These findings suggest a possible role of nitric oxide in the anxiolytic effect of chlordiazepoxide in the elevated plus maze.", "contents": "Possible involvement of nitric oxide in chlordiazepoxide-induced anxiolysis in mice. Mice challenged with the anxiolytic benzodiazepine chlordiazepoxide exhibited significant increases in the percent of total entries into and percent of total time spent on open arms of an elevated plus maze. Systemic pretreatment with the nitric oxide synthase-inhibitor L-NG-nitro arginine (L-NOARG) antagonized these effects of chlordiazepoxide. This inhibitory effect of L-NOARG was stereospecifically and completely reversed by intracerebroventricular administration of L-arginine but not D-arginine. These findings suggest a possible role of nitric oxide in the anxiolytic effect of chlordiazepoxide in the elevated plus maze."} {"id": "PMID:1280755", "title": "Stimulus-specific inhibition of insulin release from rat pancreas by both rat and porcine galanin.", "content": "The effect of the neuropeptide galanin on insulin and somatostatin secretion in the rat was studied under various conditions. In the perfused rat pancreas, insulin secretion stimulated by arginine, but not cholecystokinin-8 (CCK-8) or acetylcholine (ACh) was inhibited by both rat and porcine galanin, whereas ACh-stimulated somatostatin release was inhibited by rat but not porcine galanin. Neither arginine nor CCK-8 significantly altered somatostatin secretion and galanin was without effect under those conditions. Gastric inhibitory polypeptide-stimulated insulin release from cultured mixtures of purified rat beta- and non-beta-cells was inhibited by rat and porcine galanin in a concentration-dependent and equipotent manner. The results suggest that the inhibitory effect of galanin on insulin and somatostatin secretion may be stimulus-specific and species-specific.", "contents": "Stimulus-specific inhibition of insulin release from rat pancreas by both rat and porcine galanin. The effect of the neuropeptide galanin on insulin and somatostatin secretion in the rat was studied under various conditions. In the perfused rat pancreas, insulin secretion stimulated by arginine, but not cholecystokinin-8 (CCK-8) or acetylcholine (ACh) was inhibited by both rat and porcine galanin, whereas ACh-stimulated somatostatin release was inhibited by rat but not porcine galanin. Neither arginine nor CCK-8 significantly altered somatostatin secretion and galanin was without effect under those conditions. Gastric inhibitory polypeptide-stimulated insulin release from cultured mixtures of purified rat beta- and non-beta-cells was inhibited by rat and porcine galanin in a concentration-dependent and equipotent manner. The results suggest that the inhibitory effect of galanin on insulin and somatostatin secretion may be stimulus-specific and species-specific."} {"id": "PMID:1280756", "title": "Porcine endometrial epithelial cells immortalized by transfection with origin-defective, temperature-sensitive simian virus 40 DNA.", "content": "The purpose of this study was to immortalize porcine endometrial cells and to characterize the transformed cells. Primary porcine endometrial cells were transfected with the plasmid vector (pmk16) containing SV40 DNA using a liposome-mediated method. The viral DNA was from a replication-defective, origin-minus, temperature-sensitive mutant strain (A58). One clone, designated PE-1, has been propagated for over 120 passages. PE-1 cells grown at 33C (33C cells) exhibit spindle-shaped morphology; when cultured at 40C (40C cells), they took on a polygonal or spherical shape. Morphology of 40C cells returned to the spindle shape after culture flasks were shifted back to 33C. During a 2-week period, 33C cells propagated approximately 30-fold faster than 40C cells, whereas protein concentration was higher in 40C cells. Southern blot analysis of PE-1 cells demonstrated successful integration of the ts-SV40 DNA sequence into the porcine endometrial cells, possibly at multiple sites. The presence of cytokeratin on PE-1 cell membranes was shown by immunocytochemical studies, suggesting that the PE-1 cell clone was of epithelial origin. Reverse phase (RP)-HPLC analysis of PE-1 cell extract indicated that the majority of immunoreactive beta-endorphin (ir-BEND) eluted with a hydrophobicity similar to that of synthetic BEND and alpha-N-acetylated BEND (Nac-BEND). These results demonstrate that a porcine endometrial cell line has been established, and that this cell line possesses characteristics of temperature sensitivity in cell morphology, growth rate, and protein synthesis.", "contents": "Porcine endometrial epithelial cells immortalized by transfection with origin-defective, temperature-sensitive simian virus 40 DNA. The purpose of this study was to immortalize porcine endometrial cells and to characterize the transformed cells. Primary porcine endometrial cells were transfected with the plasmid vector (pmk16) containing SV40 DNA using a liposome-mediated method. The viral DNA was from a replication-defective, origin-minus, temperature-sensitive mutant strain (A58). One clone, designated PE-1, has been propagated for over 120 passages. PE-1 cells grown at 33C (33C cells) exhibit spindle-shaped morphology; when cultured at 40C (40C cells), they took on a polygonal or spherical shape. Morphology of 40C cells returned to the spindle shape after culture flasks were shifted back to 33C. During a 2-week period, 33C cells propagated approximately 30-fold faster than 40C cells, whereas protein concentration was higher in 40C cells. Southern blot analysis of PE-1 cells demonstrated successful integration of the ts-SV40 DNA sequence into the porcine endometrial cells, possibly at multiple sites. The presence of cytokeratin on PE-1 cell membranes was shown by immunocytochemical studies, suggesting that the PE-1 cell clone was of epithelial origin. Reverse phase (RP)-HPLC analysis of PE-1 cell extract indicated that the majority of immunoreactive beta-endorphin (ir-BEND) eluted with a hydrophobicity similar to that of synthetic BEND and alpha-N-acetylated BEND (Nac-BEND). These results demonstrate that a porcine endometrial cell line has been established, and that this cell line possesses characteristics of temperature sensitivity in cell morphology, growth rate, and protein synthesis."} {"id": "PMID:1280757", "title": "Non-linear epitopes of the large subunit of Ku autoantigen recognized by monoclonal and autoantibodies.", "content": "Sera from certain patients with SLE, scleroderma and other autoimmune diseases react with the two subunits of the Ku protein: 86 and 70 kDa. Previous experiments indicated that a region of 40 amino acids near the C-terminus of the 86 kDa subunit between amino acids 667 and 708 was critical for binding of monoclonal and some autoimmune antibodies. In the present study, a series of additional 5' deletions and site-specific mutations in the critical region were produced and the immunoreactivities of the recombinant proteins were examined. ELISA and immunoblot analyses showed that three non-competing monoclonal antibodies specific for the 86 kDa subunit require stretches of amino acids significantly longer than 40 amino acids for reactivity, suggesting that the antigen is recognized in a folded state with perhaps more than one contact point. The reactivities of 12 of 24 anti-Ku positive autoimmune sera screened depended on the same amino acid sequences required for binding of the monoclonal antibodies, site-specific mutations reduced the reactivities of monoclonal and autoantibodies in a similar way. Preincubation of native Ku protein with the monoclonal antibodies shifted the electrophoretic mobility of Ku protein-DNA complex, suggesting that these monoclonal antibodies bind to epitopes on the surface of the native Ku protein. Taken together, the results from the deletion and site-directed mutagenesis demonstrate that both monoclonal and autoantibodies recognize non-linear epitopes of the 86 kDa polypeptide. These findings indicate that in a large portion of patients the anti-Ku autoimmune response is similar to the normal immune response to the Ku antigen in mice.", "contents": "Non-linear epitopes of the large subunit of Ku autoantigen recognized by monoclonal and autoantibodies. Sera from certain patients with SLE, scleroderma and other autoimmune diseases react with the two subunits of the Ku protein: 86 and 70 kDa. Previous experiments indicated that a region of 40 amino acids near the C-terminus of the 86 kDa subunit between amino acids 667 and 708 was critical for binding of monoclonal and some autoimmune antibodies. In the present study, a series of additional 5' deletions and site-specific mutations in the critical region were produced and the immunoreactivities of the recombinant proteins were examined. ELISA and immunoblot analyses showed that three non-competing monoclonal antibodies specific for the 86 kDa subunit require stretches of amino acids significantly longer than 40 amino acids for reactivity, suggesting that the antigen is recognized in a folded state with perhaps more than one contact point. The reactivities of 12 of 24 anti-Ku positive autoimmune sera screened depended on the same amino acid sequences required for binding of the monoclonal antibodies, site-specific mutations reduced the reactivities of monoclonal and autoantibodies in a similar way. Preincubation of native Ku protein with the monoclonal antibodies shifted the electrophoretic mobility of Ku protein-DNA complex, suggesting that these monoclonal antibodies bind to epitopes on the surface of the native Ku protein. Taken together, the results from the deletion and site-directed mutagenesis demonstrate that both monoclonal and autoantibodies recognize non-linear epitopes of the 86 kDa polypeptide. These findings indicate that in a large portion of patients the anti-Ku autoimmune response is similar to the normal immune response to the Ku antigen in mice."} {"id": "PMID:1280758", "title": "Sequence diversity of T cell receptor alpha chain transcripts from BALB/c thymus.", "content": "Most of the diversity in T cell receptor subunits resides in the region that is the equivalent of the CDR3 of immunoglobulins. In order to learn more about the relative contributions of the various mechanisms that generate this diversity we have analyzed the sequences of alpha chain transcripts from BALB/c thymus. The J alpha repertoire of BALB/c mice was examined by comparison of new J alpha sequences and previously published sequences. Among the 41 J alpha genes examined, most of the diversity is located at the 5' end, consistent with the notion that this region contacts the antigen. VJ junctional diversity was examined by sequencing various V alpha J alpha combinations derived from different stages of development. Deletion of bases from the ends of V and J genes does not occur with equal frequency. A greater number of bases were deleted on average from the ends of J genes. Bases were added at junctions frequently in isolates from adult animals, consistent with the presence of terminal deoxynucleotidyl transferase. However, there were short stretches of sequences at junctions which were also present at the 5' end of J genes. These findings extend recent observations that alpha chain genes use multiple mechanisms for generating diversity.", "contents": "Sequence diversity of T cell receptor alpha chain transcripts from BALB/c thymus. Most of the diversity in T cell receptor subunits resides in the region that is the equivalent of the CDR3 of immunoglobulins. In order to learn more about the relative contributions of the various mechanisms that generate this diversity we have analyzed the sequences of alpha chain transcripts from BALB/c thymus. The J alpha repertoire of BALB/c mice was examined by comparison of new J alpha sequences and previously published sequences. Among the 41 J alpha genes examined, most of the diversity is located at the 5' end, consistent with the notion that this region contacts the antigen. VJ junctional diversity was examined by sequencing various V alpha J alpha combinations derived from different stages of development. Deletion of bases from the ends of V and J genes does not occur with equal frequency. A greater number of bases were deleted on average from the ends of J genes. Bases were added at junctions frequently in isolates from adult animals, consistent with the presence of terminal deoxynucleotidyl transferase. However, there were short stretches of sequences at junctions which were also present at the 5' end of J genes. These findings extend recent observations that alpha chain genes use multiple mechanisms for generating diversity."} {"id": "PMID:1280759", "title": "Intrinsic immunogenicity of an internal VP1 T-B epitope pair of type 1 poliovirus.", "content": "We describe the intrinsic immunogenicity of a poliovirus T-B epitope pair that is located in the N-terminus of the capsid protein VP1. This peptide is unusual in that it is located on the interior of the native virion at the VP1-VP3 interface in a region that becomes exposed after cell binding, proteolysis, or heating of the virus. Immunization of mice with either the virion or free peptide leads to anti-peptide antibody production. Anti-peptide immunity is under genetic control and 1-Ak restricted T cell proliferative responses have been identified. SJL/J (H-2s) mice that are low responders to this T-B epitope pair are also low responders to PSV-1 itself, suggesting that this site may be important in the production of neutralizing anti-PSV-1 antibodies. Interestingly, seropositive humans also have significant anti-peptide titers suggesting that immunization with poliovirus in a species permissive for infection also leads to anti-peptide antibody production. Collectively, these data suggest that a T-B epitope pair located on the interior of a protein or virion can be immunogenic. Several mechanisms whereby internal T-B epitope pairs might become immunogenic are discussed.", "contents": "Intrinsic immunogenicity of an internal VP1 T-B epitope pair of type 1 poliovirus. We describe the intrinsic immunogenicity of a poliovirus T-B epitope pair that is located in the N-terminus of the capsid protein VP1. This peptide is unusual in that it is located on the interior of the native virion at the VP1-VP3 interface in a region that becomes exposed after cell binding, proteolysis, or heating of the virus. Immunization of mice with either the virion or free peptide leads to anti-peptide antibody production. Anti-peptide immunity is under genetic control and 1-Ak restricted T cell proliferative responses have been identified. SJL/J (H-2s) mice that are low responders to this T-B epitope pair are also low responders to PSV-1 itself, suggesting that this site may be important in the production of neutralizing anti-PSV-1 antibodies. Interestingly, seropositive humans also have significant anti-peptide titers suggesting that immunization with poliovirus in a species permissive for infection also leads to anti-peptide antibody production. Collectively, these data suggest that a T-B epitope pair located on the interior of a protein or virion can be immunogenic. Several mechanisms whereby internal T-B epitope pairs might become immunogenic are discussed."} {"id": "PMID:1280760", "title": "Unique biochemical properties of a mutant MHC class I molecule, H-2Ksm1.", "content": "This study describes serological and biochemical properties of a novel MHC class I molecule. The mutant H-2Ksm1 molecule was discovered in a mouse because of loss of reactivity of its peripheral blood lymphocytes to monoclonal antibodies. This mutation in the H-2Ks molecule is the first in vivo mutation described that has altered an amino acid residue (amino acid 107) distant from the regions generally considered to be peptide or TCR contacts. Cell surface expression of the mutant molecules remains high but the Arg107 to Trp substitution appears to alter the native protein conformation, markedly decreasing cell surface association with beta 2-microglobulin light chains and conferring a loss of recognition by Ks specific antibodies.", "contents": "Unique biochemical properties of a mutant MHC class I molecule, H-2Ksm1. This study describes serological and biochemical properties of a novel MHC class I molecule. The mutant H-2Ksm1 molecule was discovered in a mouse because of loss of reactivity of its peripheral blood lymphocytes to monoclonal antibodies. This mutation in the H-2Ks molecule is the first in vivo mutation described that has altered an amino acid residue (amino acid 107) distant from the regions generally considered to be peptide or TCR contacts. Cell surface expression of the mutant molecules remains high but the Arg107 to Trp substitution appears to alter the native protein conformation, markedly decreasing cell surface association with beta 2-microglobulin light chains and conferring a loss of recognition by Ks specific antibodies."} {"id": "PMID:1280761", "title": "Human anti-acetylcholine receptor antibodies use variable gene segments analogous to those used in autoantibodies of various specificities.", "content": "The production of autoantibodies to the nicotinic acetylcholine receptor are responsible for many of the neurological symptoms observed in myasthenia gravis. An understanding of the structural organization of the anti-receptor antibodies may help to define the role of these antibodies in the pathogenesis of this disease. The nucleotide sequences of the heavy and light chains of three human monoclonal anti-receptor antibodies isolated from peripheral blood lymphocytes from two patients with myasthenia gravis were analyzed. In addition, the structure of an anti-idiotypic antibody was studied. The VH and VL gene segments used in the anti-receptor antibodies appear to be derived from the same repertoire as gene segments that have been found in other autoantibodies isolated from patients with various autoimmune diseases. The IgM anti-receptor antibodies are direct copies of germline gene segments, while the structures of the IgG anti-receptor antibody and the anti-idiotypic antibody appear to be mutated suggesting that they have undergone antigenic selection.", "contents": "Human anti-acetylcholine receptor antibodies use variable gene segments analogous to those used in autoantibodies of various specificities. The production of autoantibodies to the nicotinic acetylcholine receptor are responsible for many of the neurological symptoms observed in myasthenia gravis. An understanding of the structural organization of the anti-receptor antibodies may help to define the role of these antibodies in the pathogenesis of this disease. The nucleotide sequences of the heavy and light chains of three human monoclonal anti-receptor antibodies isolated from peripheral blood lymphocytes from two patients with myasthenia gravis were analyzed. In addition, the structure of an anti-idiotypic antibody was studied. The VH and VL gene segments used in the anti-receptor antibodies appear to be derived from the same repertoire as gene segments that have been found in other autoantibodies isolated from patients with various autoimmune diseases. The IgM anti-receptor antibodies are direct copies of germline gene segments, while the structures of the IgG anti-receptor antibody and the anti-idiotypic antibody appear to be mutated suggesting that they have undergone antigenic selection."} {"id": "PMID:1280762", "title": "Profile of the regions on the alpha-chain of human acetylcholine receptor recognized by autoantibodies in myasthenia gravis.", "content": "Eighteen synthetic overlapping peptides encompassing the entire extracellular part (residues alpha 1-210) of the alpha-chain of human acetylcholine receptor (AChR) and a 19th peptide (residues alpha 262-276) corresponding to an extracellular connection between two transmembrane regions were prepared and used for the measurement, by solid-phase radioimmunoassay, of the binding of autoantibodies in plasma from myasthenia gravis (MG) patients. Autoantibodies were found to recognize only a limited number of the synthetic peptides. The regions recognized resided predominantly within the areas alpha 10-30, alpha 111-145 and alpha 175-198 and, less frequently, region alpha 45-77. Differences in the recognition profile of the peptides from patient to patient indicated that the autoantibody responses were under genetic control. However, by using a mixture of the appropriate peptides, it was possible to determine autoantibodies in all 15 myasthenia sera and to distinguish between these, normal human sera and other neurological or autoimmune diseases. The mapping of the continuous antigenic regions recognized by autoantibodies on the alpha-chain of human AChR has permitted a comparison of the regions recognized by autoantibodies and autoimmune T-cells from the same donor. It also provided a peptide-based direct antibody binding method for diagnosis of MG.", "contents": "Profile of the regions on the alpha-chain of human acetylcholine receptor recognized by autoantibodies in myasthenia gravis. Eighteen synthetic overlapping peptides encompassing the entire extracellular part (residues alpha 1-210) of the alpha-chain of human acetylcholine receptor (AChR) and a 19th peptide (residues alpha 262-276) corresponding to an extracellular connection between two transmembrane regions were prepared and used for the measurement, by solid-phase radioimmunoassay, of the binding of autoantibodies in plasma from myasthenia gravis (MG) patients. Autoantibodies were found to recognize only a limited number of the synthetic peptides. The regions recognized resided predominantly within the areas alpha 10-30, alpha 111-145 and alpha 175-198 and, less frequently, region alpha 45-77. Differences in the recognition profile of the peptides from patient to patient indicated that the autoantibody responses were under genetic control. However, by using a mixture of the appropriate peptides, it was possible to determine autoantibodies in all 15 myasthenia sera and to distinguish between these, normal human sera and other neurological or autoimmune diseases. The mapping of the continuous antigenic regions recognized by autoantibodies on the alpha-chain of human AChR has permitted a comparison of the regions recognized by autoantibodies and autoimmune T-cells from the same donor. It also provided a peptide-based direct antibody binding method for diagnosis of MG."} {"id": "PMID:1280771", "title": "The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team.", "content": "Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.", "contents": "The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team. Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease."} {"id": "PMID:1280770", "title": "[Mobilization using incompatibility group P1 plasmids in strains of Pseudomonas pseudomallei and Pseudomonas mallei as potential vectors for DNA cloning].", "content": "The cells of Pseudomonas pseudomallei and Pseudomonas mallei have been shown to serve as recipients for the plasmid RSF1010 and its recombinant derivatives pVA1 and pVA4. The conjugative plasmids RP1 and pTH10 of the incompatibility group P1 are able to mobilize the nontransmissive vector plasmids for conjugation transfer into Pseudomonas pseudomallei and Pseudomonas mallei strains. The SmR determinant of the plasmid RSF1010 is expressed in the latter strains. These data makes the mentioned vector plasmids the candidates for DNA cloning in these strains.", "contents": "[Mobilization using incompatibility group P1 plasmids in strains of Pseudomonas pseudomallei and Pseudomonas mallei as potential vectors for DNA cloning]. The cells of Pseudomonas pseudomallei and Pseudomonas mallei have been shown to serve as recipients for the plasmid RSF1010 and its recombinant derivatives pVA1 and pVA4. The conjugative plasmids RP1 and pTH10 of the incompatibility group P1 are able to mobilize the nontransmissive vector plasmids for conjugation transfer into Pseudomonas pseudomallei and Pseudomonas mallei strains. The SmR determinant of the plasmid RSF1010 is expressed in the latter strains. These data makes the mentioned vector plasmids the candidates for DNA cloning in these strains."} {"id": "PMID:1280773", "title": "Altered structure and expression of the p53 gene in human neuroepithelial tumors.", "content": "The p53 gene, located on chromosome 17p13.1, may be important in the pathogenesis of human neuroepithelial tumors, because it is a tumor suppressor gene and genetic alteration is essential for certain human cells to acquire the neoplastic phenotype. The structure and expression of the p53 gene were investigated in cultured human glioma cells and biopsied specimens of neuroepithelial tumors. Immunocytochemical examination of p53 gene expression revealed positive nuclear staining in six of seven glioma cell lines tested. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis demonstrated unequivocal heterogeneity of migration rate in p53 bands. Pulse-chase analysis clearly showed an increased half-life of p53 in cultured human glioma cells. These abnormalities are presumably due to genetic alterations in the p53 gene. Nucleotide substitutions in exon 5, 7, or 8 of the p53 gene could be detected by polymerase chain reaction-single strand conformational polymorphic analysis in four of seven (57%) human glioma cell lines, and nine of 29 (31%) biopsied specimens of neuroepithelial tumors examined. The present results indicate that genetic alterations in the p53 gene are responsible for the tumorigenesis of at least some human neuroepithelial tumors.", "contents": "Altered structure and expression of the p53 gene in human neuroepithelial tumors. The p53 gene, located on chromosome 17p13.1, may be important in the pathogenesis of human neuroepithelial tumors, because it is a tumor suppressor gene and genetic alteration is essential for certain human cells to acquire the neoplastic phenotype. The structure and expression of the p53 gene were investigated in cultured human glioma cells and biopsied specimens of neuroepithelial tumors. Immunocytochemical examination of p53 gene expression revealed positive nuclear staining in six of seven glioma cell lines tested. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis demonstrated unequivocal heterogeneity of migration rate in p53 bands. Pulse-chase analysis clearly showed an increased half-life of p53 in cultured human glioma cells. These abnormalities are presumably due to genetic alterations in the p53 gene. Nucleotide substitutions in exon 5, 7, or 8 of the p53 gene could be detected by polymerase chain reaction-single strand conformational polymorphic analysis in four of seven (57%) human glioma cell lines, and nine of 29 (31%) biopsied specimens of neuroepithelial tumors examined. The present results indicate that genetic alterations in the p53 gene are responsible for the tumorigenesis of at least some human neuroepithelial tumors."} {"id": "PMID:1280774", "title": "Cerebral vein disorders and postoperative brain damage associated with the pterional approach in aneurysm surgery.", "content": "The possible causes of postoperative brain damage were examined in 100 cases of cerebral aneurysms operated on by the pterional approach. Postoperative brain damage occurred in 15% of cases, located mostly in the inferior frontal lobe. Its incidence was higher in early than in delayed operation and increased with severity of preoperative clinical conditions but not correlated with patient age and aneurysm location. The venous perfusion patterns in the inferior frontal lobe were classified into three types based on preoperative venograms: Sylvian type drained mainly into the superficial Sylvian veins (SSVs), Frontal type drained mainly into the frontal bridging veins, and Intermediate type. Postoperative brain damage was most frequent in the Sylvian type with statistical significance (p < 0.01). The brain retraction procedure impairs regional cerebral blood flow (rCBF). Venous congestion in the retracted inferior frontal lobe, caused by stretching and narrowing of SSVs due to both brain retraction and dissection of the Sylvian fissure, also reduces rCBF. Thus, a marked reduction in rCBF in the retracted area causes postoperative brain damage. Postoperative venograms showed the SSVs to be obscured in 24% of patients, indicating that the pterional approach possibly influences the SSV perfusion. A venous perfusion disorder during the pterional approach is the most important factor in postoperative brain damage, and careful preoperative assessment of cerebral veins is indispensable.", "contents": "Cerebral vein disorders and postoperative brain damage associated with the pterional approach in aneurysm surgery. The possible causes of postoperative brain damage were examined in 100 cases of cerebral aneurysms operated on by the pterional approach. Postoperative brain damage occurred in 15% of cases, located mostly in the inferior frontal lobe. Its incidence was higher in early than in delayed operation and increased with severity of preoperative clinical conditions but not correlated with patient age and aneurysm location. The venous perfusion patterns in the inferior frontal lobe were classified into three types based on preoperative venograms: Sylvian type drained mainly into the superficial Sylvian veins (SSVs), Frontal type drained mainly into the frontal bridging veins, and Intermediate type. Postoperative brain damage was most frequent in the Sylvian type with statistical significance (p < 0.01). The brain retraction procedure impairs regional cerebral blood flow (rCBF). Venous congestion in the retracted inferior frontal lobe, caused by stretching and narrowing of SSVs due to both brain retraction and dissection of the Sylvian fissure, also reduces rCBF. Thus, a marked reduction in rCBF in the retracted area causes postoperative brain damage. Postoperative venograms showed the SSVs to be obscured in 24% of patients, indicating that the pterional approach possibly influences the SSV perfusion. A venous perfusion disorder during the pterional approach is the most important factor in postoperative brain damage, and careful preoperative assessment of cerebral veins is indispensable."} {"id": "PMID:1280775", "title": "Preliminary results of interstitial 192Ir brachytherapy for malignant gliomas.", "content": "Twenty-six patients with recurrent or unremovable malignant gliomas were treated by interstitial brachytherapy with iridium-192 seeds. Stereotactic implantation of the afterloading catheters using the Brown-Roberts-Wells computed tomography (CT)-guided stereotactic system was performed in 24 patients and surgical implantation in two patients with pontine glioma. The response to therapy was measured by serial CT, magnetic resonance imaging, and clinical examination. Tumor regression was seen in 17 patients 1-3 months after implantation. Tumor progression was seen in only three patients. After interstitial brachytherapy, the most commonly observed CT finding was central low density. Median survival time was 18 months after implantation. Autopsies in five patients revealed the delayed effects of radiation injury such as typical vascular changes, microcalcification, and coagulative necrosis in the implant area and tumor recurrence at the periphery. The results suggest that brachytherapy is not curative but prolonged the median survival time by 6 months.", "contents": "Preliminary results of interstitial 192Ir brachytherapy for malignant gliomas. Twenty-six patients with recurrent or unremovable malignant gliomas were treated by interstitial brachytherapy with iridium-192 seeds. Stereotactic implantation of the afterloading catheters using the Brown-Roberts-Wells computed tomography (CT)-guided stereotactic system was performed in 24 patients and surgical implantation in two patients with pontine glioma. The response to therapy was measured by serial CT, magnetic resonance imaging, and clinical examination. Tumor regression was seen in 17 patients 1-3 months after implantation. Tumor progression was seen in only three patients. After interstitial brachytherapy, the most commonly observed CT finding was central low density. Median survival time was 18 months after implantation. Autopsies in five patients revealed the delayed effects of radiation injury such as typical vascular changes, microcalcification, and coagulative necrosis in the implant area and tumor recurrence at the periphery. The results suggest that brachytherapy is not curative but prolonged the median survival time by 6 months."} {"id": "PMID:1280776", "title": "A provocative internal carotid artery balloon occlusion test with 99mTc-HM-PAO CBF mapping--report of three cases.", "content": "The balloon occlusion test (BOT) of the internal carotid artery (ICA), combined with induced hypotension and cerebral blood flow (CBF) mapping, was carried out in three patients with a large or giant aneurysm of the ICA. Occlusion of the ICA for 10 minutes in the normotensive state was followed by 5 minutes of induced hypotension. During the last 2 minutes of hypotensive occlusion, technetium-99m-hexamethyl-propyleneamine oxime was administered to study the CBF. All patients tolerated the procedure well. One patient with moderate CBF reduction developed ischemic complications 24 hours after permanent ICA occlusion. Another showed no significant change in CBF and tolerated permanent ICA occlusion well, while the third refused permanent occlusion. The provocative BOT combined with CBF mapping is a promising predictor of complications of ICA occlusion secondary to perfusion abnormalities.", "contents": "A provocative internal carotid artery balloon occlusion test with 99mTc-HM-PAO CBF mapping--report of three cases. The balloon occlusion test (BOT) of the internal carotid artery (ICA), combined with induced hypotension and cerebral blood flow (CBF) mapping, was carried out in three patients with a large or giant aneurysm of the ICA. Occlusion of the ICA for 10 minutes in the normotensive state was followed by 5 minutes of induced hypotension. During the last 2 minutes of hypotensive occlusion, technetium-99m-hexamethyl-propyleneamine oxime was administered to study the CBF. All patients tolerated the procedure well. One patient with moderate CBF reduction developed ischemic complications 24 hours after permanent ICA occlusion. Another showed no significant change in CBF and tolerated permanent ICA occlusion well, while the third refused permanent occlusion. The provocative BOT combined with CBF mapping is a promising predictor of complications of ICA occlusion secondary to perfusion abnormalities."} {"id": "PMID:1280777", "title": "Moyamoya disease associated with pituitary adenoma--report of two cases.", "content": "Moyamoya disease associated with prolactin (PRL)-producing pituitary adenomas occurred in two females with elevated blood PRL levels (285 and 120 ng/ml). Computed tomography revealed cystic tumors extending from the sella turcica to the suprasellar cistern. Carotid angiography demonstrated stenoses or obstructions of the bilateral internal carotid arteries at their end point and development of bilateral basal moyamoya vessels. Histological diagnosis in one case was PRL-producing chromophobe adenoma. No stigmata of neurofibromatosis or any history of irradiation was found. Compression of carotid arteries by the tumor was unlikely. These cases should therefore be classified as moyamoya disease accompanied by brain tumor, a very rare occurrence. The hypothalamic disturbance caused by moyamoya disease may have induced the hyperprolactinemia, resulting in secondary prolactinoma.", "contents": "Moyamoya disease associated with pituitary adenoma--report of two cases. Moyamoya disease associated with prolactin (PRL)-producing pituitary adenomas occurred in two females with elevated blood PRL levels (285 and 120 ng/ml). Computed tomography revealed cystic tumors extending from the sella turcica to the suprasellar cistern. Carotid angiography demonstrated stenoses or obstructions of the bilateral internal carotid arteries at their end point and development of bilateral basal moyamoya vessels. Histological diagnosis in one case was PRL-producing chromophobe adenoma. No stigmata of neurofibromatosis or any history of irradiation was found. Compression of carotid arteries by the tumor was unlikely. These cases should therefore be classified as moyamoya disease accompanied by brain tumor, a very rare occurrence. The hypothalamic disturbance caused by moyamoya disease may have induced the hyperprolactinemia, resulting in secondary prolactinoma."} {"id": "PMID:1280778", "title": "Intracranial extension of an orbital pseudotumor accompanied by internal carotid artery occlusion--case report.", "content": "A rare case of histologically verified orbital pseudotumor with intracranial extension in a 33-year-old male is reported. Preoperative radiographs showed the mass extending beyond the orbit and involving the bilateral cavernous sinuses. The intracranial lesion at biopsy surrounded the right internal carotid artery above the right cavernous sinus. Cerebral angiography showed complete occlusion of the cervical portion of the right internal carotid artery. Possibly, multiple lesions had extended contiguously through the venous system around the cavernous sinus, with subsequent involvement of the internal carotid artery. This case suggests that orbital pseudotumor may not be a separate clinical entity, but a part of the syndrome caused by inflammation of the venous system around the cavernous sinus.", "contents": "Intracranial extension of an orbital pseudotumor accompanied by internal carotid artery occlusion--case report. A rare case of histologically verified orbital pseudotumor with intracranial extension in a 33-year-old male is reported. Preoperative radiographs showed the mass extending beyond the orbit and involving the bilateral cavernous sinuses. The intracranial lesion at biopsy surrounded the right internal carotid artery above the right cavernous sinus. Cerebral angiography showed complete occlusion of the cervical portion of the right internal carotid artery. Possibly, multiple lesions had extended contiguously through the venous system around the cavernous sinus, with subsequent involvement of the internal carotid artery. This case suggests that orbital pseudotumor may not be a separate clinical entity, but a part of the syndrome caused by inflammation of the venous system around the cavernous sinus."} {"id": "PMID:1280779", "title": "Cavernous angioma of the cerebellum and cerebellar atrophy--case report.", "content": "A cavernous angioma of the cerebellum occurred in a 55-year-old female presenting with a 3-year history of slowly progressive cerebellar signs and symptoms. Computed tomography and magnetic resonance imaging revealed a lesion in the left cerebellar nuclei and atrophic change of the affected cerebellar hemisphere. The final diagnosis was made at operation. The cerebellar nuclei and white matter were probably affected by the slowly expanding lesion, with repeated hemorrhage leading to degeneration of the afferent and efferent fibers, and subsequent atrophy of the affected cerebellar hemisphere.", "contents": "Cavernous angioma of the cerebellum and cerebellar atrophy--case report. A cavernous angioma of the cerebellum occurred in a 55-year-old female presenting with a 3-year history of slowly progressive cerebellar signs and symptoms. Computed tomography and magnetic resonance imaging revealed a lesion in the left cerebellar nuclei and atrophic change of the affected cerebellar hemisphere. The final diagnosis was made at operation. The cerebellar nuclei and white matter were probably affected by the slowly expanding lesion, with repeated hemorrhage leading to degeneration of the afferent and efferent fibers, and subsequent atrophy of the affected cerebellar hemisphere."} {"id": "PMID:1280780", "title": "Diaphragma sellae meningioma associated only with signs of hypopituitarism--case report.", "content": "A rare diaphragma sellae meningioma presenting only with signs of hypopituitarism occurred in a 54-year-old male. Preoperative magnetic resonance (MR) imaging clearly demonstrated a small lesion in the supradiaphragmatic area immediately beneath the optic chiasm, displacing the pituitary stalk laterally. Intraoperatively, the tumor was confirmed to be attached only to the posterior leaf of the diaphragma sellae. Histological examination revealed a transitional type meningioma. Such a small meningioma may be associated only with hypopituitarism, as compression is confined to the pituitary stalk, not affecting the optic pathways. MR imaging can demonstrate the clinicopathological features of this small but significant tumor.", "contents": "Diaphragma sellae meningioma associated only with signs of hypopituitarism--case report. A rare diaphragma sellae meningioma presenting only with signs of hypopituitarism occurred in a 54-year-old male. Preoperative magnetic resonance (MR) imaging clearly demonstrated a small lesion in the supradiaphragmatic area immediately beneath the optic chiasm, displacing the pituitary stalk laterally. Intraoperatively, the tumor was confirmed to be attached only to the posterior leaf of the diaphragma sellae. Histological examination revealed a transitional type meningioma. Such a small meningioma may be associated only with hypopituitarism, as compression is confined to the pituitary stalk, not affecting the optic pathways. MR imaging can demonstrate the clinicopathological features of this small but significant tumor."} {"id": "PMID:1280781", "title": "Hemichorea associated with ipsilateral chronic subdural hematoma--case report.", "content": "Left-sided hemichorea developed suddenly in a 73-year-old male. Computed tomography revealed a left subdural hematoma (SDH) and infarction in the right corona radiata and temporo-occipital region. Hemichorea subsided completely after removal of the SDH. Postoperative single photon emission computed tomography with technetium-99m-hexamethyl-propyleneamine oxime revealed a global low-perfusion area in the right cerebral hemisphere. Right carotid angiography demonstrated severe stenosis of the trunk of the right middle cerebral artery. The cerebral blood flow in the right cerebral hemisphere had probably already decreased to nearly the critical level and was reduced further by the left SDH, inducing the left-sided hemichorea due to dysfunction of the right cerebral hemisphere. This case shows that when hemichorea ipsilateral to a SDH is present, it is important to ascertain whether there is a pre-existing ischemic lesion in the contralateral cerebral hemisphere, particularly in the basal ganglia, thalamus, or corona radiata.", "contents": "Hemichorea associated with ipsilateral chronic subdural hematoma--case report. Left-sided hemichorea developed suddenly in a 73-year-old male. Computed tomography revealed a left subdural hematoma (SDH) and infarction in the right corona radiata and temporo-occipital region. Hemichorea subsided completely after removal of the SDH. Postoperative single photon emission computed tomography with technetium-99m-hexamethyl-propyleneamine oxime revealed a global low-perfusion area in the right cerebral hemisphere. Right carotid angiography demonstrated severe stenosis of the trunk of the right middle cerebral artery. The cerebral blood flow in the right cerebral hemisphere had probably already decreased to nearly the critical level and was reduced further by the left SDH, inducing the left-sided hemichorea due to dysfunction of the right cerebral hemisphere. This case shows that when hemichorea ipsilateral to a SDH is present, it is important to ascertain whether there is a pre-existing ischemic lesion in the contralateral cerebral hemisphere, particularly in the basal ganglia, thalamus, or corona radiata."} {"id": "PMID:1280782", "title": "Magnetic resonance findings in spontaneous dissection of the cervical internal carotid artery--case report.", "content": "The magnetic resonance (MR) appearance of a spontaneous dissection of the cervical internal carotid artery (ICA) in a 53-year-old male is described. Cerebral angiograms demonstrated a long-segment stenosis of the left cervical ICA beginning above the common carotid bifurcation and extending to the skull base (\"string sign\"). T1-, T2-, and proton density-weighted MR images of the upper neck revealed a high-intensity crescent mass expanding the arterial wall and narrowing the arterial lumen of the left ICA. This high-intensity mass was considered to represent the mural hematoma of the involved ICA. Gradual improvement of the dissection was confirmed by both angiography and MR imaging. Cerebral angiograms have shown pathognomonic findings such as double lumen and intimal flap in only some patients with ICA dissection. Our experience suggests that MR demonstration of the mural hematoma is specific and important for diagnosis and follow-up in cases of spontaneous dissection of the cervical ICA.", "contents": "Magnetic resonance findings in spontaneous dissection of the cervical internal carotid artery--case report. The magnetic resonance (MR) appearance of a spontaneous dissection of the cervical internal carotid artery (ICA) in a 53-year-old male is described. Cerebral angiograms demonstrated a long-segment stenosis of the left cervical ICA beginning above the common carotid bifurcation and extending to the skull base (\"string sign\"). T1-, T2-, and proton density-weighted MR images of the upper neck revealed a high-intensity crescent mass expanding the arterial wall and narrowing the arterial lumen of the left ICA. This high-intensity mass was considered to represent the mural hematoma of the involved ICA. Gradual improvement of the dissection was confirmed by both angiography and MR imaging. Cerebral angiograms have shown pathognomonic findings such as double lumen and intimal flap in only some patients with ICA dissection. Our experience suggests that MR demonstration of the mural hematoma is specific and important for diagnosis and follow-up in cases of spontaneous dissection of the cervical ICA."} {"id": "PMID:1280783", "title": "Giant aneurysm at the junction of the left internal carotid and persistent primitive trigeminal arteries--case report.", "content": "A 67-year-old female presented with an unruptured giant aneurysm at the junction of the left internal carotid artery (ICA) and the persistent primitive trigeminal artery (PTA), manifesting as progressive left abducens nerve paresis. The PTA was clipped by the left suboccipital approach. The aneurysm was then successfully thrombosed by ligation of the left ICA at the cervical portion following left superficial temporal artery-middle cerebral artery anastomosis. The left abducens nerve paresis improved postoperatively. Magnetic resonance imaging was of considerable value in the pre- and postoperative evaluation of the giant aneurysm.", "contents": "Giant aneurysm at the junction of the left internal carotid and persistent primitive trigeminal arteries--case report. A 67-year-old female presented with an unruptured giant aneurysm at the junction of the left internal carotid artery (ICA) and the persistent primitive trigeminal artery (PTA), manifesting as progressive left abducens nerve paresis. The PTA was clipped by the left suboccipital approach. The aneurysm was then successfully thrombosed by ligation of the left ICA at the cervical portion following left superficial temporal artery-middle cerebral artery anastomosis. The left abducens nerve paresis improved postoperatively. Magnetic resonance imaging was of considerable value in the pre- and postoperative evaluation of the giant aneurysm."} {"id": "PMID:1280786", "title": "Major histocompatibility complex (MHC) antigen expression in HIV encephalitis.", "content": "In order to study possible immunopathogenic mechanisms in Human Immunodeficiency Virus (HIV) encephalitis, immunocytochemical localization of Class I and Class II major histocompatibility complex (MHC) antigens was studied in formalin-fixed tissue sections from the brains of 10 individuals who had died with this disorder. Using the avidin biotin peroxidase technique and monoclonal antibodies to these antigens, increased expression of Class I antigens was found in five out of 10 and of Class II antigens in six out of 10 cases of HIV encephalitis. This contrasted with results obtained with the HIV-specific anti-P24 antibody which reacted with only a small number of cells in four cases. Class I and II antigens were detected mainly in perivascular monocytes/macrophages and also in multinucleated giant cells. In two cases, slight labelling was also detected in these cells more diffusely in the brain parenchyma. Immune and viral antigens were not detected in glial cells or neurons. Neither normal control cases nor brain sections from patients who had died from other neurological diseases were labelled with any of the antibodies apart from two cases of varicella-zoster virus-associated encephalitis in which increased expression of Class II antigens occurred. These findings support the notion that indirect immune-mediated mechanisms may be important in the pathogenesis of HIV encephalitis.", "contents": "Major histocompatibility complex (MHC) antigen expression in HIV encephalitis. In order to study possible immunopathogenic mechanisms in Human Immunodeficiency Virus (HIV) encephalitis, immunocytochemical localization of Class I and Class II major histocompatibility complex (MHC) antigens was studied in formalin-fixed tissue sections from the brains of 10 individuals who had died with this disorder. Using the avidin biotin peroxidase technique and monoclonal antibodies to these antigens, increased expression of Class I antigens was found in five out of 10 and of Class II antigens in six out of 10 cases of HIV encephalitis. This contrasted with results obtained with the HIV-specific anti-P24 antibody which reacted with only a small number of cells in four cases. Class I and II antigens were detected mainly in perivascular monocytes/macrophages and also in multinucleated giant cells. In two cases, slight labelling was also detected in these cells more diffusely in the brain parenchyma. Immune and viral antigens were not detected in glial cells or neurons. Neither normal control cases nor brain sections from patients who had died from other neurological diseases were labelled with any of the antibodies apart from two cases of varicella-zoster virus-associated encephalitis in which increased expression of Class II antigens occurred. These findings support the notion that indirect immune-mediated mechanisms may be important in the pathogenesis of HIV encephalitis."} {"id": "PMID:1280784", "title": "[Effect of elimination of supratentorial aneurysms by micro- surgical method on early structural and functional changes near the operation site].", "content": "On the basis of neurological, psychological and computed tomographic studies of the head early consequences of microsurgical elimination of supratentorial brain aneurysms were analysed in a group of 37 patients. It was shown that this method of aneurysm treatment may lead to brain oedema near the operation site. Oedema development was observed most frequently in cases of prolonged pressure exerted by spatulae on the brain tissue during the operation, aneurysm location in the anterior cerebral artery system and in cases operated on from 4 to 10 days after subarachnoid haemorrhage.", "contents": "[Effect of elimination of supratentorial aneurysms by micro- surgical method on early structural and functional changes near the operation site]. On the basis of neurological, psychological and computed tomographic studies of the head early consequences of microsurgical elimination of supratentorial brain aneurysms were analysed in a group of 37 patients. It was shown that this method of aneurysm treatment may lead to brain oedema near the operation site. Oedema development was observed most frequently in cases of prolonged pressure exerted by spatulae on the brain tissue during the operation, aneurysm location in the anterior cerebral artery system and in cases operated on from 4 to 10 days after subarachnoid haemorrhage."} {"id": "PMID:1280787", "title": "[Pro9]SP and [pGlu6, Pro9]SP(6-11) interact with two different receptors in the guinea-pig ileum as demonstrated with new SP antagonists.", "content": "Structural considerations led us to postulate that the introduction of the dipeptides DPro9-Pro10 and DPro9-MeLeu10 should lock the C-terminal tetrapeptide of SP in a type II' beta-turn structure, a prerequisite for antagonist activity. Indeed, as the GR 71251, [DPro9, Pro10, Trp11]SP was more potent in inhibiting the septide, (pA2 = 6.5), than the [Pro9]SP, (pA2 < or = 5), spasmogenic activity in the guinea-pig ileum bioassay. This result confirms that septide, [pGlu6, Pro9]SP(6-11), a peptide active in the guinea-pig ileum bioassay and practically devoid of binding potencies for the three specific NK-1, NK-2 and NK-3 tachykinin binding sites interacts with a tachykinin receptor different from the NK-1 receptor sensitive to [Pro9]SP. Interestingly enough, the reintroduction of the leucine side-chain in position 10 yielded [DPro9, MeLeu10, Trp11]SP, an antagonist, equipotent in inhibiting both the septide- and the [Pro9]SP-evoked contractile response in the guinea-pig ileum bioassay, (pA2 = 6.6).", "contents": "[Pro9]SP and [pGlu6, Pro9]SP(6-11) interact with two different receptors in the guinea-pig ileum as demonstrated with new SP antagonists. Structural considerations led us to postulate that the introduction of the dipeptides DPro9-Pro10 and DPro9-MeLeu10 should lock the C-terminal tetrapeptide of SP in a type II' beta-turn structure, a prerequisite for antagonist activity. Indeed, as the GR 71251, [DPro9, Pro10, Trp11]SP was more potent in inhibiting the septide, (pA2 = 6.5), than the [Pro9]SP, (pA2 < or = 5), spasmogenic activity in the guinea-pig ileum bioassay. This result confirms that septide, [pGlu6, Pro9]SP(6-11), a peptide active in the guinea-pig ileum bioassay and practically devoid of binding potencies for the three specific NK-1, NK-2 and NK-3 tachykinin binding sites interacts with a tachykinin receptor different from the NK-1 receptor sensitive to [Pro9]SP. Interestingly enough, the reintroduction of the leucine side-chain in position 10 yielded [DPro9, MeLeu10, Trp11]SP, an antagonist, equipotent in inhibiting both the septide- and the [Pro9]SP-evoked contractile response in the guinea-pig ileum bioassay, (pA2 = 6.6)."} {"id": "PMID:1280785", "title": "[2 cases of ischemic cerebral stroke in a young man with hyperlipidemia type IV].", "content": "In a young man at the age of 29 and 35 years without risk factors for atherosclerosis and, consequently, cerebrovascular disease two severe strokes of atypical clinical pattern developed leading to considerable impairment of psychomotor fitness. Diagnostic tests and study of family members demonstrated familial hyperlipidaemia type IV.", "contents": "[2 cases of ischemic cerebral stroke in a young man with hyperlipidemia type IV]. In a young man at the age of 29 and 35 years without risk factors for atherosclerosis and, consequently, cerebrovascular disease two severe strokes of atypical clinical pattern developed leading to considerable impairment of psychomotor fitness. Diagnostic tests and study of family members demonstrated familial hyperlipidaemia type IV."} {"id": "PMID:1280788", "title": "Central substance P increased blood pressure, heart rate and splanchnic nerve activity in anaesthetized rats without impairment of the baroreflex regulation.", "content": "In anaesthetized rats the baroreflex was checked before and 15 min after i.c.v. administration of 10 micrograms SP. The baroreflex was checked indirectly by relating both the reflex prolongation in heart period (inter-beat-interval: IBI) and the reflex inhibition of SNA to a pharmacologically induced BP rise. After i.c.v. administration of SP (n = 10) the resting values of the BP increased significantly from 73 +/- 16 mm Hg to 86 +/- 9 mm Hg (diastolic pressure) and from 98 +/- 20 mm Hg to 113 +/- 14 mm Hg (systolic pressure) whilst in the control group (n = 14) the BP remained constant (63 +/- 9 vs 63 +/- 7 mm Hg diastolic pressure and 106 +/- 12 vs 106 +/- 9 mm Hg systolic pressure). In the experimental group the resting value in IBI was shortened significantly from 218 +/- 40 ms to 167 +/- 28 ms (controls: 218 +/- 22 ms vs 218 +/- 18 ms) and the SNA (estimated in arbitrary units) rose significantly by about 50% in relation to the reference period before i.c.v. SP (3.31 +/- 0.11 vs 6.27 +/- 0.17 arbitrary units per IBI). In contrast, the baroreflex behaved similarly before and after any treatment, i.e. both the reflex prolongation in IBI (1.34 +/- 0.75 vs 1.39 +/- 0.95 ms/mm Hg) and the reflex inhibition of SNA (0.0312 +/- 0.01 vs 0.0555 +/- 0.015 arbitrary units/mm Hg) caused by that pharmacologically induced BP rise were comparable before and after i.c.v. SP.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Central substance P increased blood pressure, heart rate and splanchnic nerve activity in anaesthetized rats without impairment of the baroreflex regulation. In anaesthetized rats the baroreflex was checked before and 15 min after i.c.v. administration of 10 micrograms SP. The baroreflex was checked indirectly by relating both the reflex prolongation in heart period (inter-beat-interval: IBI) and the reflex inhibition of SNA to a pharmacologically induced BP rise. After i.c.v. administration of SP (n = 10) the resting values of the BP increased significantly from 73 +/- 16 mm Hg to 86 +/- 9 mm Hg (diastolic pressure) and from 98 +/- 20 mm Hg to 113 +/- 14 mm Hg (systolic pressure) whilst in the control group (n = 14) the BP remained constant (63 +/- 9 vs 63 +/- 7 mm Hg diastolic pressure and 106 +/- 12 vs 106 +/- 9 mm Hg systolic pressure). In the experimental group the resting value in IBI was shortened significantly from 218 +/- 40 ms to 167 +/- 28 ms (controls: 218 +/- 22 ms vs 218 +/- 18 ms) and the SNA (estimated in arbitrary units) rose significantly by about 50% in relation to the reference period before i.c.v. SP (3.31 +/- 0.11 vs 6.27 +/- 0.17 arbitrary units per IBI). In contrast, the baroreflex behaved similarly before and after any treatment, i.e. both the reflex prolongation in IBI (1.34 +/- 0.75 vs 1.39 +/- 0.95 ms/mm Hg) and the reflex inhibition of SNA (0.0312 +/- 0.01 vs 0.0555 +/- 0.015 arbitrary units/mm Hg) caused by that pharmacologically induced BP rise were comparable before and after i.c.v. SP.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280789", "title": "Galanin message-associated peptide (GMAP)- and galanin-like immunoreactivities: overlapping and differential distributions in the rat.", "content": "Using the indirect immunofluorescence method the distribution of galanin message associated peptide (GMAP)- and galanin-like immunoreactivities (LI) was compared in brain, intestine and some endocrine tissues of rat. In general, neurons in the peripheral and central nervous system contained both immunoreactivities. However, in retina the cones were GMAP-positive but galanin-negative. A strong GMAP-LI was observed in the prolactin cells in the anterior lobe of the pituitary and in the insulin cells in the islets of Langerhans in the pancreas, whereas incubation with galanin antiserum resulted in staining of fewer cells (anterior pituitary) or a very weak fluorescence (pancreas). The results show that most neurons express both GMAP- and galanin-LI, but raise the possibility that in some systems there is a tissue specific, posttranslational differential processing of preprogalanin.", "contents": "Galanin message-associated peptide (GMAP)- and galanin-like immunoreactivities: overlapping and differential distributions in the rat. Using the indirect immunofluorescence method the distribution of galanin message associated peptide (GMAP)- and galanin-like immunoreactivities (LI) was compared in brain, intestine and some endocrine tissues of rat. In general, neurons in the peripheral and central nervous system contained both immunoreactivities. However, in retina the cones were GMAP-positive but galanin-negative. A strong GMAP-LI was observed in the prolactin cells in the anterior lobe of the pituitary and in the insulin cells in the islets of Langerhans in the pancreas, whereas incubation with galanin antiserum resulted in staining of fewer cells (anterior pituitary) or a very weak fluorescence (pancreas). The results show that most neurons express both GMAP- and galanin-LI, but raise the possibility that in some systems there is a tissue specific, posttranslational differential processing of preprogalanin."} {"id": "PMID:1280790", "title": "Identification of neurons expressing thyrotropin releasing-hormone receptor mRNA in spinal cord and lower brainstem of rat.", "content": "The distribution of mRNA coding for a pituitary thyrotropin releasing-hormone (TRH) receptor was examined on sections of spinal cord and lower brainstem of rat using in situ hybridization. Hybridization signals were observed over large neurons in the ventral horn in cervical, thoracic, and lumbar segments of spinal cord, and over neurons in the motor nuclei of the lower brainstem. Although significant thyrotropin-releasing hormone binding has been reported in the superficial dorsal horn, only background levels of hybridization were observed over neurons in this region. These findings suggest that mRNA coding for thyrotropin-releasing hormone receptor is expressed in some spinal and brainstem motor neurons. Since many of these neurons are innervated by TRH-containing afferents, TRH may exert a direct effect upon at least some of these cells.", "contents": "Identification of neurons expressing thyrotropin releasing-hormone receptor mRNA in spinal cord and lower brainstem of rat. The distribution of mRNA coding for a pituitary thyrotropin releasing-hormone (TRH) receptor was examined on sections of spinal cord and lower brainstem of rat using in situ hybridization. Hybridization signals were observed over large neurons in the ventral horn in cervical, thoracic, and lumbar segments of spinal cord, and over neurons in the motor nuclei of the lower brainstem. Although significant thyrotropin-releasing hormone binding has been reported in the superficial dorsal horn, only background levels of hybridization were observed over neurons in this region. These findings suggest that mRNA coding for thyrotropin-releasing hormone receptor is expressed in some spinal and brainstem motor neurons. Since many of these neurons are innervated by TRH-containing afferents, TRH may exert a direct effect upon at least some of these cells."} {"id": "PMID:1280791", "title": "The distribution of angiotensin II AT1 receptor subtype mRNA in the rat brain.", "content": "The present study demonstrates the existence and regional distribution of angiotensin II AT1 receptor subtype mRNA expression in the rat brain by the use of in situ hybridization and RNase protection assay. Substantial expression levels in the brain have only been detected in certain distinct areas, such as the subfornical organ, the parvocellular part of the paraventricular hypothalamic nucleus, and the median preoptic nucleus. The results give further evidence for the involvement of the angiotensin II AT1 receptor subtype in the classical functions of central angiotensin II, like blood pressure control, body fluid homeostasis and in corticotropin-releasing factor (CRF) secretion.", "contents": "The distribution of angiotensin II AT1 receptor subtype mRNA in the rat brain. The present study demonstrates the existence and regional distribution of angiotensin II AT1 receptor subtype mRNA expression in the rat brain by the use of in situ hybridization and RNase protection assay. Substantial expression levels in the brain have only been detected in certain distinct areas, such as the subfornical organ, the parvocellular part of the paraventricular hypothalamic nucleus, and the median preoptic nucleus. The results give further evidence for the involvement of the angiotensin II AT1 receptor subtype in the classical functions of central angiotensin II, like blood pressure control, body fluid homeostasis and in corticotropin-releasing factor (CRF) secretion."} {"id": "PMID:1280792", "title": "Enhanced neurite growth in cultured neuroblastoma cells exposed to aluminum.", "content": "Patients with aluminum-induced encephalopathy syndromes have been shown to have a high level of aluminum concentration in the brain. In the present study, the effects of aluminum were studied in mouse neuroblastoma cells (N-2A) grown in medium supplemented with aluminum (100 microM). It was found that aluminum enhanced neurite growth within 2 days of exposure. The mean total length of neurites in the control after 14 days in culture was 29.8 +/- 4.7 microns, whereas the neurite length of cells pre-exposed to aluminum for 2 days and then maintained in normal media for an additional 12 days was 56.4 +/- 8.9 microns. Further, the duration of exposure did not significantly promote a greater neurite response. The neurite length of cells exposed to aluminum for 14 days (60.7 +/- 9.6 microns) was not statistically different from that of cells exposed to aluminum for 2 days. Using morin stain, intracellular aluminum was detected within 24 h of exposure in the majority of aluminum-exposed cells. Intracellular aluminum did not disappear from those cells even after they were grown for 12 days in control medium. Our finding suggests that a brief exposure (2 days) to low level aluminum (100 microM) is sufficient to cause long-lasting effects on the morphology of neuroblastoma cells in culture. Such neurite behavior associated with aluminum exposure may suggest a morphological basis for the dementia seen in aluminum encephalopathy.", "contents": "Enhanced neurite growth in cultured neuroblastoma cells exposed to aluminum. Patients with aluminum-induced encephalopathy syndromes have been shown to have a high level of aluminum concentration in the brain. In the present study, the effects of aluminum were studied in mouse neuroblastoma cells (N-2A) grown in medium supplemented with aluminum (100 microM). It was found that aluminum enhanced neurite growth within 2 days of exposure. The mean total length of neurites in the control after 14 days in culture was 29.8 +/- 4.7 microns, whereas the neurite length of cells pre-exposed to aluminum for 2 days and then maintained in normal media for an additional 12 days was 56.4 +/- 8.9 microns. Further, the duration of exposure did not significantly promote a greater neurite response. The neurite length of cells exposed to aluminum for 14 days (60.7 +/- 9.6 microns) was not statistically different from that of cells exposed to aluminum for 2 days. Using morin stain, intracellular aluminum was detected within 24 h of exposure in the majority of aluminum-exposed cells. Intracellular aluminum did not disappear from those cells even after they were grown for 12 days in control medium. Our finding suggests that a brief exposure (2 days) to low level aluminum (100 microM) is sufficient to cause long-lasting effects on the morphology of neuroblastoma cells in culture. Such neurite behavior associated with aluminum exposure may suggest a morphological basis for the dementia seen in aluminum encephalopathy."} {"id": "PMID:1280793", "title": "NBQX (6-nitro-sulfamoyl-benzo-quinoxaline-dione) and CPP (3-carboxy-piperazin-propyl phosphonic acid) potentiate dopamine agonist induced rotations in substantia nigra lesioned rats.", "content": "Degeneration of dopaminergic nigrostriatal neurons in primate models of Parkinson's disease (PD) leads to an overactivity of excitatory glutamatergic projections from the subthalamic nucleus (STN) to the output nuclei of the basal ganglia resulting in rigidity and akinesia. The selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist 6-nitro-sulfamoyl-benzo-quinoxaline-dione (NBQX) and the competitive N-methyl-D-aspartate (NMDA) antagonist 3-carboxy-piperazin-propyl phosphonic acid (CPP) ameliorate parkinsonian symptomatology when co-administered with threshold doses of L-DOPA in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets and induce rotations in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra (SN). Here we report that in the 6-OHDA-lesioned rat NBQX and CPP induce contralateral rotations when combined with threshold doses of the direct dopamine agonists lisuride or apomorphine. AMPA antagonists and competitive NMDA antagonists may therefore be suitable as adjuvants for the treatment of PD.", "contents": "NBQX (6-nitro-sulfamoyl-benzo-quinoxaline-dione) and CPP (3-carboxy-piperazin-propyl phosphonic acid) potentiate dopamine agonist induced rotations in substantia nigra lesioned rats. Degeneration of dopaminergic nigrostriatal neurons in primate models of Parkinson's disease (PD) leads to an overactivity of excitatory glutamatergic projections from the subthalamic nucleus (STN) to the output nuclei of the basal ganglia resulting in rigidity and akinesia. The selective alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) antagonist 6-nitro-sulfamoyl-benzo-quinoxaline-dione (NBQX) and the competitive N-methyl-D-aspartate (NMDA) antagonist 3-carboxy-piperazin-propyl phosphonic acid (CPP) ameliorate parkinsonian symptomatology when co-administered with threshold doses of L-DOPA in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets and induce rotations in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra (SN). Here we report that in the 6-OHDA-lesioned rat NBQX and CPP induce contralateral rotations when combined with threshold doses of the direct dopamine agonists lisuride or apomorphine. AMPA antagonists and competitive NMDA antagonists may therefore be suitable as adjuvants for the treatment of PD."} {"id": "PMID:1280794", "title": "Miniature postsynaptic currents recorded from identified rat spinal dorsal horn projection neurons in thin-slice preparations.", "content": "Whole-cell voltage-clamp recordings were made from spinothalamic and spinomesencephalic tract neurons in thin-slice preparations of rat spinal cord. In the presence of tetrodotoxin, spontaneous inward and outward postsynaptic currents were observed near the resting membrane potential. These currents were divided into miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate, and miniature inhibitory postsynaptic currents (mIPSCs) mediated by glycine or gamma-aminobutyric acid (GABA). Glutamatergic mEPSCs had two components mediated by NMDA and non-NMDA receptors. Analyzing these miniature synaptic currents, valuable information concerning the pre- and postsynaptic mechanisms underlying modulation of synaptic transmission in the spinal dorsal horn could be obtained.", "contents": "Miniature postsynaptic currents recorded from identified rat spinal dorsal horn projection neurons in thin-slice preparations. Whole-cell voltage-clamp recordings were made from spinothalamic and spinomesencephalic tract neurons in thin-slice preparations of rat spinal cord. In the presence of tetrodotoxin, spontaneous inward and outward postsynaptic currents were observed near the resting membrane potential. These currents were divided into miniature excitatory postsynaptic currents (mEPSCs) mediated by glutamate, and miniature inhibitory postsynaptic currents (mIPSCs) mediated by glycine or gamma-aminobutyric acid (GABA). Glutamatergic mEPSCs had two components mediated by NMDA and non-NMDA receptors. Analyzing these miniature synaptic currents, valuable information concerning the pre- and postsynaptic mechanisms underlying modulation of synaptic transmission in the spinal dorsal horn could be obtained."} {"id": "PMID:1280795", "title": "Origins of parasympathetic postganglionic vasodilator fibers supplying the lips and gingivae; an WGA-HRP study in the cat.", "content": "Application of WGA-HRP to the mandibular lip and buccal gingiva of the cat resulted in retrograde labeling in the ipsilateral otic ganglion (OG), whereas labeled neurons appeared in the pterygopalatine ganglion (PPG) as well as in the OG when the tracer was injected into the maxillary lip and buccal gingiva. The results suggest that both the facial and the glossopharyngeal preganglionic vasodilator fibers supplying the mandibular lip and buccal gingiva mediated in the OG, and those innervating the maxillary lip and buccal gingiva are mediated in the PPG and the OG.", "contents": "Origins of parasympathetic postganglionic vasodilator fibers supplying the lips and gingivae; an WGA-HRP study in the cat. Application of WGA-HRP to the mandibular lip and buccal gingiva of the cat resulted in retrograde labeling in the ipsilateral otic ganglion (OG), whereas labeled neurons appeared in the pterygopalatine ganglion (PPG) as well as in the OG when the tracer was injected into the maxillary lip and buccal gingiva. The results suggest that both the facial and the glossopharyngeal preganglionic vasodilator fibers supplying the mandibular lip and buccal gingiva mediated in the OG, and those innervating the maxillary lip and buccal gingiva are mediated in the PPG and the OG."} {"id": "PMID:1280796", "title": "An after-depolarization following action potentials and its modulation by substance P in rat sympathetic neurons.", "content": "Sympathetic neurons in rat coeliac-superior mesenteric ganglia (C-SMG) displayed an after-depolarization (ADP) following action potentials and after-hyperpolarization. The ADP had amplitudes of 3-10 mV and lasted for 2-6 s, during which membrane resistance and excitability of C-SMG neurons increased. The reversal potential of ADP was dependent on external K+ concentrations. The ADP was suppressed in a solution containing Cd2+ or zero Ca2+. The ADP thus appears to be produced by inhibition of certain K+ channels via a Ca(2+)-dependent process. Substances P (SP) depolarized ganglion cells and increased the ADP, leading to a long-lasting increase in membrane excitability of rat C-SMG neurons.", "contents": "An after-depolarization following action potentials and its modulation by substance P in rat sympathetic neurons. Sympathetic neurons in rat coeliac-superior mesenteric ganglia (C-SMG) displayed an after-depolarization (ADP) following action potentials and after-hyperpolarization. The ADP had amplitudes of 3-10 mV and lasted for 2-6 s, during which membrane resistance and excitability of C-SMG neurons increased. The reversal potential of ADP was dependent on external K+ concentrations. The ADP was suppressed in a solution containing Cd2+ or zero Ca2+. The ADP thus appears to be produced by inhibition of certain K+ channels via a Ca(2+)-dependent process. Substances P (SP) depolarized ganglion cells and increased the ADP, leading to a long-lasting increase in membrane excitability of rat C-SMG neurons."} {"id": "PMID:1280798", "title": "Multifocal choroiditis and choroidal neovascularization associated with the multiple evanescent white dot and acute idiopathic blind spot enlargement syndrome.", "content": "Several recent articles have described syndromes in which there is enlargement of the blind spot associated with retinal lesions. These have included the multiple evanescent white dot syndrome, acute macular neuroretinopathy, acute idiopathic blind spot enlargement syndrome, and multifocal choroiditis or pseudo presumed ocular histoplasmosis syndrome (pseudo POHS). The authors reviewed the records of seven patients in whom signs and symptoms of acute enlargement of the blind spot and pseudo POHS developed. All seven patients had photopsia accompanying enlargement of the blind spot during their illness. Four had transient white spots as seen in the multiple evanescent white dot syndrome. All presented with or developed chorioretinal scars or neovascularization similar to that seen in multifocal choroiditis or pseudo POHS. In four of the seven patients, POHS-like scars developed only in the eye that was symptomatic with blind spot enlargement and photopsia. Five of the 7 had visual acuity of 20/25 or better at the last follow-up. It would appear that there is an overlap in the clinical findings of all of these syndromes and that there may be a common link in their etiology.", "contents": "Multifocal choroiditis and choroidal neovascularization associated with the multiple evanescent white dot and acute idiopathic blind spot enlargement syndrome. Several recent articles have described syndromes in which there is enlargement of the blind spot associated with retinal lesions. These have included the multiple evanescent white dot syndrome, acute macular neuroretinopathy, acute idiopathic blind spot enlargement syndrome, and multifocal choroiditis or pseudo presumed ocular histoplasmosis syndrome (pseudo POHS). The authors reviewed the records of seven patients in whom signs and symptoms of acute enlargement of the blind spot and pseudo POHS developed. All seven patients had photopsia accompanying enlargement of the blind spot during their illness. Four had transient white spots as seen in the multiple evanescent white dot syndrome. All presented with or developed chorioretinal scars or neovascularization similar to that seen in multifocal choroiditis or pseudo POHS. In four of the seven patients, POHS-like scars developed only in the eye that was symptomatic with blind spot enlargement and photopsia. Five of the 7 had visual acuity of 20/25 or better at the last follow-up. It would appear that there is an overlap in the clinical findings of all of these syndromes and that there may be a common link in their etiology."} {"id": "PMID:1280799", "title": "Preliminary assessment of the Dex Frame for assisting children with specific learning difficulties.", "content": "A device called the Dex Frame has recently been marketed as an aid for children with specific learning difficulties. Using a test of reading speed and a test of reading accuracy we have attempted to evaluate the device. Two groups of children with learning difficulties were used, one having sole use of the device and being allowed to carry it with them and a second group who only used the device when attending for remedial tuition and assessment. The results show that no significant improvement occurred in reading performance of the groups with learning difficulties using the Dex Frame as compared with a control group. The teachers of the groups did, however, feel that on an individual basis some children (< 10%) expressed that they felt more comfortable using the device.", "contents": "Preliminary assessment of the Dex Frame for assisting children with specific learning difficulties. A device called the Dex Frame has recently been marketed as an aid for children with specific learning difficulties. Using a test of reading speed and a test of reading accuracy we have attempted to evaluate the device. Two groups of children with learning difficulties were used, one having sole use of the device and being allowed to carry it with them and a second group who only used the device when attending for remedial tuition and assessment. The results show that no significant improvement occurred in reading performance of the groups with learning difficulties using the Dex Frame as compared with a control group. The teachers of the groups did, however, feel that on an individual basis some children (< 10%) expressed that they felt more comfortable using the device."} {"id": "PMID:1280800", "title": "Medical students' attitudes toward pain before and after a brief course on pain.", "content": "The effectiveness of a brief clinical and basic science seminar on pain for 1st year medical students was examined by comparing attitudes about pain prior to the seminar to attitudes 5 months after the seminar. The 6-h course combined written materials conveying facts about behavioral, social and biological aspects of pain with clinical observations of an acute and a chronic pain treatment team. Examination of responses to a questionnaire assessing attitudes toward pain patients revealed that medical students have limited personal experience with pain and medications for pain, and limited knowledge about pain. Pre-course attitudes toward pain patients were dominated by perceived negative characteristics of pain patients and the belief that working with such patients is difficult. Attitudes measured 5 months after the course reflected increased complexity, greater emphasis that pain is real and not imaginary, and stronger belief that working with pain patients is rewarding. Five months after the seminar, students reported more accurate estimates of the frequency of problems with addiction stemming from acute pain treatment and exaggerated the prevalence of pain problems in the society. The importance of integrating clinical and basic science experiences in order to influence long-term clinical attitudes and produce lasting changes in clinically relevant knowledge is discussed.", "contents": "Medical students' attitudes toward pain before and after a brief course on pain. The effectiveness of a brief clinical and basic science seminar on pain for 1st year medical students was examined by comparing attitudes about pain prior to the seminar to attitudes 5 months after the seminar. The 6-h course combined written materials conveying facts about behavioral, social and biological aspects of pain with clinical observations of an acute and a chronic pain treatment team. Examination of responses to a questionnaire assessing attitudes toward pain patients revealed that medical students have limited personal experience with pain and medications for pain, and limited knowledge about pain. Pre-course attitudes toward pain patients were dominated by perceived negative characteristics of pain patients and the belief that working with such patients is difficult. Attitudes measured 5 months after the course reflected increased complexity, greater emphasis that pain is real and not imaginary, and stronger belief that working with pain patients is rewarding. Five months after the seminar, students reported more accurate estimates of the frequency of problems with addiction stemming from acute pain treatment and exaggerated the prevalence of pain problems in the society. The importance of integrating clinical and basic science experiences in order to influence long-term clinical attitudes and produce lasting changes in clinically relevant knowledge is discussed."} {"id": "PMID:1280801", "title": "Regression to the mean in treated versus untreated chronic pain.", "content": "The course of pain associated with temporomandibular disorders (TMD) and other chronic pain conditions is typically episodic. Its expression may influence when a person seeks treatment, for example, when the level of pain flares up or exceeds its characteristic severity. Improvement in pain status subsequent to entering treatment may be due to: (1) specific effects of treatment; (2) non-specific effects of treatment ('placebo effects'); or (3) regression to the mean. Due to regression to the mean, uncontrolled evaluation of treatment in persons self-selected by a pain flare-up may lead to erroneous conclusions concerning effects of treatment by patients, providers, and/or researchers. For this report, the magnitude of regression to the mean due to self-selection for treatment is estimated by comparing subjects who sought treatment for TMD pain (n = 147) to a random sample of subjects with TMD pain not seeking treatment (n = 95). Among subjects seeking treatment, a significant 14.7-point reduction in VAS pain intensity was observed at 1-year follow-up. A control group of TMD subjects not seeking treatment showed no mean reduction in pain intensity but reported lower pain intensity at baseline than the group seeking care. When both groups of subjects were stratified on baseline VAS pain values, the reduction in pain increased as the baseline pain level increased, but no differences between comparable treated and untreated cases in the extent of improvement were observed. The before-after differences in both groups may be attributed to regression to the mean.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Regression to the mean in treated versus untreated chronic pain. The course of pain associated with temporomandibular disorders (TMD) and other chronic pain conditions is typically episodic. Its expression may influence when a person seeks treatment, for example, when the level of pain flares up or exceeds its characteristic severity. Improvement in pain status subsequent to entering treatment may be due to: (1) specific effects of treatment; (2) non-specific effects of treatment ('placebo effects'); or (3) regression to the mean. Due to regression to the mean, uncontrolled evaluation of treatment in persons self-selected by a pain flare-up may lead to erroneous conclusions concerning effects of treatment by patients, providers, and/or researchers. For this report, the magnitude of regression to the mean due to self-selection for treatment is estimated by comparing subjects who sought treatment for TMD pain (n = 147) to a random sample of subjects with TMD pain not seeking treatment (n = 95). Among subjects seeking treatment, a significant 14.7-point reduction in VAS pain intensity was observed at 1-year follow-up. A control group of TMD subjects not seeking treatment showed no mean reduction in pain intensity but reported lower pain intensity at baseline than the group seeking care. When both groups of subjects were stratified on baseline VAS pain values, the reduction in pain increased as the baseline pain level increased, but no differences between comparable treated and untreated cases in the extent of improvement were observed. The before-after differences in both groups may be attributed to regression to the mean.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280802", "title": "Ibuprofen plus codeine, ibuprofen, and placebo in a single- and multidose cross-over comparison for coxarthrosis pain.", "content": "The analgesic efficacy of 200 mg ibuprofen plus 30 mg codeine, 200 mg ibuprofen and placebo was investigated in a new analgesic evaluation model using single- and repeated-dose administration. The study was a double-blind randomized cross-over investigation in 26 coxarthrosis patients with persistent pain. After a washout period of at least 2 days with paracetamol available as rescue analgesic, each of the 3 treatments was administered in a total of 6 doses during 24 h. The hourly pain intensity was recorded on a 100-mm visual analogue scale (VAS) for 8 h after the 1st and the 6th dose. The pretreatment VAS score was 31-37 mm. After the 1st dose the 8-h mean pain intensity values were 25, 27, and 26 mm after ibuprofen plus codeine, ibuprofen, and placebo, respectively. Following another 5 doses every 4 h the corresponding values were 10, 17 and 29 mm. Repeated administration of both active drugs reduced the pain intensity significantly. The analgesic efficacy of ibuprofen plus codeine was significantly superior to that of ibuprofen which was, in turn, superior to that of placebo. In conclusion, analgesic efficacy was better differentiated after repeated-dose than after single-dose administration. The present study design was able to differentiate between 200 mg ibuprofen plus 30 mg codeine and 200 mg ibuprofen alone in a relatively small number of patients.", "contents": "Ibuprofen plus codeine, ibuprofen, and placebo in a single- and multidose cross-over comparison for coxarthrosis pain. The analgesic efficacy of 200 mg ibuprofen plus 30 mg codeine, 200 mg ibuprofen and placebo was investigated in a new analgesic evaluation model using single- and repeated-dose administration. The study was a double-blind randomized cross-over investigation in 26 coxarthrosis patients with persistent pain. After a washout period of at least 2 days with paracetamol available as rescue analgesic, each of the 3 treatments was administered in a total of 6 doses during 24 h. The hourly pain intensity was recorded on a 100-mm visual analogue scale (VAS) for 8 h after the 1st and the 6th dose. The pretreatment VAS score was 31-37 mm. After the 1st dose the 8-h mean pain intensity values were 25, 27, and 26 mm after ibuprofen plus codeine, ibuprofen, and placebo, respectively. Following another 5 doses every 4 h the corresponding values were 10, 17 and 29 mm. Repeated administration of both active drugs reduced the pain intensity significantly. The analgesic efficacy of ibuprofen plus codeine was significantly superior to that of ibuprofen which was, in turn, superior to that of placebo. In conclusion, analgesic efficacy was better differentiated after repeated-dose than after single-dose administration. The present study design was able to differentiate between 200 mg ibuprofen plus 30 mg codeine and 200 mg ibuprofen alone in a relatively small number of patients."} {"id": "PMID:1280803", "title": "An effect of ascorbic acid on delayed-onset muscle soreness.", "content": "Delayed-onset muscle soreness following strenuous use of the posterior calf muscles was studied to determine if ascorbic acid might have an effect on the appearance of this familiar pain. A double-blind, randomized, crossover study compared the soreness in subjects taking ascorbic acid against those taking a lactose placebo. Visual analog scales were used in conjunction with a variety of pain-challenging methods, and the results indicated a significant difference between experimental and placebo groups at the height of soreness. Typical soreness abatement scores of 25-44% were observed. A sample size of 19, lack of an untreated control group as well as the singular nature of the exercise and its intensity were considered limitations of the study.", "contents": "An effect of ascorbic acid on delayed-onset muscle soreness. Delayed-onset muscle soreness following strenuous use of the posterior calf muscles was studied to determine if ascorbic acid might have an effect on the appearance of this familiar pain. A double-blind, randomized, crossover study compared the soreness in subjects taking ascorbic acid against those taking a lactose placebo. Visual analog scales were used in conjunction with a variety of pain-challenging methods, and the results indicated a significant difference between experimental and placebo groups at the height of soreness. Typical soreness abatement scores of 25-44% were observed. A sample size of 19, lack of an untreated control group as well as the singular nature of the exercise and its intensity were considered limitations of the study."} {"id": "PMID:1280804", "title": "Alterations in neuronal excitability and the potency of spinal mu, delta and kappa opioids after carrageenan-induced inflammation.", "content": "These electrophysiological results show that the development of inflammation following peripheral injection of carrageenan into the paw is accompanied by alterations in the magnitude of the C-fibre evoked response of multireceptive dorsal horn neurones. The evoked response of the dorsal horn cells was found to either increase or decrease in the 3 h following the carrageenan injection, and the direction of this change was related to the degree of wind-up exhibited by the cell. Regardless of whether a cell was facilitated or inhibited by carrageenan, mu, delta and kappa opioids applied topically onto the spinal cord (equivalent to an intrathecal injection) exhibited increased antinociceptive potency. This increased effectiveness was especially marked for the mu opioid, morphine, which showed a 30-fold increase in potency. Interestingly the facilitations seen with the lowest doses of the mu and kappa opioids in this model in normal animals were absent after carrageenan. In addition, a very low dose of spinal naloxone caused a small but significant reduction in the C-fibre evoked responses. These results demonstrate that following peripheral inflammation, functional changes develop in both spinal transmission and modulatory systems. Alterations in the antinociceptive potency of opioid agonists occurs, with the mu agonist, morphine, showing the greatest change.", "contents": "Alterations in neuronal excitability and the potency of spinal mu, delta and kappa opioids after carrageenan-induced inflammation. These electrophysiological results show that the development of inflammation following peripheral injection of carrageenan into the paw is accompanied by alterations in the magnitude of the C-fibre evoked response of multireceptive dorsal horn neurones. The evoked response of the dorsal horn cells was found to either increase or decrease in the 3 h following the carrageenan injection, and the direction of this change was related to the degree of wind-up exhibited by the cell. Regardless of whether a cell was facilitated or inhibited by carrageenan, mu, delta and kappa opioids applied topically onto the spinal cord (equivalent to an intrathecal injection) exhibited increased antinociceptive potency. This increased effectiveness was especially marked for the mu opioid, morphine, which showed a 30-fold increase in potency. Interestingly the facilitations seen with the lowest doses of the mu and kappa opioids in this model in normal animals were absent after carrageenan. In addition, a very low dose of spinal naloxone caused a small but significant reduction in the C-fibre evoked responses. These results demonstrate that following peripheral inflammation, functional changes develop in both spinal transmission and modulatory systems. Alterations in the antinociceptive potency of opioid agonists occurs, with the mu agonist, morphine, showing the greatest change."} {"id": "PMID:1280805", "title": "Pathology of fatal and resolving Plasmodium berghei cerebral malaria in mice.", "content": "CBA/T6 and Balb/c mice inoculated with Plasmodium berghei ANKA strain (PbA) died from cerebral malaria 6-8 days post-inoculation. DBA/2J mice similarly inoculated developed a non-fatal cerebral malaria, with mild temporary cerebral symptoms, and died between days 15 and 22 from other malaria-related complications. When inoculated with P. berghei K173 (Pb) these mouse strains did not develop a cerebral malaria but died between days 15 and 22 from other malaria-related complications. These mouse strain/parasite strain combinations allow for detailed examination of factors critical in the pathology of murine cerebral malaria. Monastral Blue, a colloid dye, when injected intravascularly between days 0 and 2 into PbA-inoculated CBA (PbA-CBA) or Balb/c (PbA-Balb/c) mice prevented death from cerebral malaria. There was no evidence of increased vascular permeability at this stage. When Monastral Blue was injected between days 5 and 8, there was increased vascular permeability in the kidney, liver, lung, spleen and brain of PbA-CBA and PbA-Balb/c mice. Injection of Monastral Blue into these animals at this time also precipitated cerebral symptoms and death, but not in Pb-infected mice. Endothelial and mononuclear cells phagocytosed, and were coated with, the Monastral Blue particles when the dye was injected between days 5 and 8 into PbA-CBA and PbA-Balb/c mice. Control, uninfected mice did not demonstrate either of these features. Pb-infected mice only demonstrated coated mononuclear cells. Mononuclear cell attachment to the endothelium, increased vascular permeability and increased association of Monastral Blue particles with monocytes and endothelial cells were correlated with cerebral symptoms and death. Monastral Blue is thus a useful agent for studying the roles of mononuclear cells and endothelium in murine cerebral malaria.", "contents": "Pathology of fatal and resolving Plasmodium berghei cerebral malaria in mice. CBA/T6 and Balb/c mice inoculated with Plasmodium berghei ANKA strain (PbA) died from cerebral malaria 6-8 days post-inoculation. DBA/2J mice similarly inoculated developed a non-fatal cerebral malaria, with mild temporary cerebral symptoms, and died between days 15 and 22 from other malaria-related complications. When inoculated with P. berghei K173 (Pb) these mouse strains did not develop a cerebral malaria but died between days 15 and 22 from other malaria-related complications. These mouse strain/parasite strain combinations allow for detailed examination of factors critical in the pathology of murine cerebral malaria. Monastral Blue, a colloid dye, when injected intravascularly between days 0 and 2 into PbA-inoculated CBA (PbA-CBA) or Balb/c (PbA-Balb/c) mice prevented death from cerebral malaria. There was no evidence of increased vascular permeability at this stage. When Monastral Blue was injected between days 5 and 8, there was increased vascular permeability in the kidney, liver, lung, spleen and brain of PbA-CBA and PbA-Balb/c mice. Injection of Monastral Blue into these animals at this time also precipitated cerebral symptoms and death, but not in Pb-infected mice. Endothelial and mononuclear cells phagocytosed, and were coated with, the Monastral Blue particles when the dye was injected between days 5 and 8 into PbA-CBA and PbA-Balb/c mice. Control, uninfected mice did not demonstrate either of these features. Pb-infected mice only demonstrated coated mononuclear cells. Mononuclear cell attachment to the endothelium, increased vascular permeability and increased association of Monastral Blue particles with monocytes and endothelial cells were correlated with cerebral symptoms and death. Monastral Blue is thus a useful agent for studying the roles of mononuclear cells and endothelium in murine cerebral malaria."} {"id": "PMID:1280806", "title": "Structure determination of two new amino acid-containing derivatives of adenosine from tRNA of thermophilic bacteria and archaea.", "content": "Two new nucleosides have been identified in unfractionated transfer RNA of two thermophilic bacteria, Thermodesulfobacterium commune, and Thermotoga maritima, six hyperthermophilic archaea, including Pyrobaculum islandicum, Pyrococcus furiosus and Thermococcus sp. and two mesophilic archaea, Methanococcus vannielii and Methanolobus tindarius. Structures were determined primarily by mass spectrometry, as 3-hydroxy-N-[[(9-beta-D-ribofuranosyl-9H-purin-6- yl)amino]carbonyl]norvaline, (hn6A), structure 1, and 3-hydroxy-N-[[(9-beta-D-ribofuranosyl-9H-2-methylthiopurin-6- yl)amino]carbonyl]norvaline (ms2hn6A), 2. The amino acid side chain was characterized as 3-hydroxynorvaline (3) by gas chromatography-mass spectrometry of the trimethylsilyl derivative after cleavage from 1 and 2 by alkaline hydrolysis. Evidence for the amino acid-purine carbamoyl linkage was obtained from the collision-induced dissociation mass spectrum of trimethylsilylated 1, and the total structure was confirmed by chemical synthesis of 1.", "contents": "Structure determination of two new amino acid-containing derivatives of adenosine from tRNA of thermophilic bacteria and archaea. Two new nucleosides have been identified in unfractionated transfer RNA of two thermophilic bacteria, Thermodesulfobacterium commune, and Thermotoga maritima, six hyperthermophilic archaea, including Pyrobaculum islandicum, Pyrococcus furiosus and Thermococcus sp. and two mesophilic archaea, Methanococcus vannielii and Methanolobus tindarius. Structures were determined primarily by mass spectrometry, as 3-hydroxy-N-[[(9-beta-D-ribofuranosyl-9H-purin-6- yl)amino]carbonyl]norvaline, (hn6A), structure 1, and 3-hydroxy-N-[[(9-beta-D-ribofuranosyl-9H-2-methylthiopurin-6- yl)amino]carbonyl]norvaline (ms2hn6A), 2. The amino acid side chain was characterized as 3-hydroxynorvaline (3) by gas chromatography-mass spectrometry of the trimethylsilyl derivative after cleavage from 1 and 2 by alkaline hydrolysis. Evidence for the amino acid-purine carbamoyl linkage was obtained from the collision-induced dissociation mass spectrum of trimethylsilylated 1, and the total structure was confirmed by chemical synthesis of 1."} {"id": "PMID:1280807", "title": "Molecular mimicry in translational control of E. coli threonyl-tRNA synthetase gene. Competitive inhibition in tRNA aminoacylation and operator-repressor recognition switch using tRNA identity rules.", "content": "We previously showed that: (i) E.coli threonyl-tRNA synthetase (ThrRS) binds to the leader of its mRNA and represses translation by preventing ribosome binding to its loading site; (ii) the translational operator shares sequence and structure similarities with tRNA(Thr); (iii) it is possible to switch the specificity of the translational control from ThrRS to methionyl-tRNA synthetase (MetRS) by changing the CGU anticodon-like sequence to CAU, the tRNA(Met) anticodon. Here, we show that the wild type (CGU) and the mutated (CAU) operators act as competitive inhibitors of tRNA(Thr) and tRNA(fMet) for aminoacylation catalyzed by E.coli ThrRS and MetRS, respectively. The apparent Kd of the MetRS/CAU operator complex is one order magnitude higher than that of the ThrRS/CGU operator complex. Although ThrRS and MetRS shield the anticodon- and acceptor-like domains of their respective operators, the relative contribution of these two domains differs significantly. As in the threonine system, the interaction of MetRS with the CAU operator occludes ribosome binding to its loading site. The present data demonstrate that the anticodon-like sequence is one major determinant for the identity of the operator and the regulation specificity. It further shows that the tRNA-like operator obeys to tRNA identity rules.", "contents": "Molecular mimicry in translational control of E. coli threonyl-tRNA synthetase gene. Competitive inhibition in tRNA aminoacylation and operator-repressor recognition switch using tRNA identity rules. We previously showed that: (i) E.coli threonyl-tRNA synthetase (ThrRS) binds to the leader of its mRNA and represses translation by preventing ribosome binding to its loading site; (ii) the translational operator shares sequence and structure similarities with tRNA(Thr); (iii) it is possible to switch the specificity of the translational control from ThrRS to methionyl-tRNA synthetase (MetRS) by changing the CGU anticodon-like sequence to CAU, the tRNA(Met) anticodon. Here, we show that the wild type (CGU) and the mutated (CAU) operators act as competitive inhibitors of tRNA(Thr) and tRNA(fMet) for aminoacylation catalyzed by E.coli ThrRS and MetRS, respectively. The apparent Kd of the MetRS/CAU operator complex is one order magnitude higher than that of the ThrRS/CGU operator complex. Although ThrRS and MetRS shield the anticodon- and acceptor-like domains of their respective operators, the relative contribution of these two domains differs significantly. As in the threonine system, the interaction of MetRS with the CAU operator occludes ribosome binding to its loading site. The present data demonstrate that the anticodon-like sequence is one major determinant for the identity of the operator and the regulation specificity. It further shows that the tRNA-like operator obeys to tRNA identity rules."} {"id": "PMID:1280808", "title": "A ribozyme with DNA in the hybridising arms displays enhanced cleavage ability.", "content": "Hammerhead ribozymes cleave RNA substrates containing the UX sequence, where X = U, C or A, embedded within sequences which are complementary to the hybridising 'arms' of the ribozyme. In this study we have replaced the RNA in the hybridising arms of the ribozyme with DNA, and the resulting ribozyme is many times more active than its precursor. In turnover-kinetics experiments with a 13-mer RNA substrate, the kcat/Km ratios are 10 and 150 microM-1min-1 for the RNA- and DNA-armed ribozymes, respectively. The effect is due mainly to differences in kcat. In independent experiments where the cleavage step is rate-limiting, the DNA-armed ribozyme cleaves the substrate with a rate constant more than 3 times greater than the all-RNA ribozyme. DNA substrates containing a ribocytidine at the cleavage site have been shown to be cleaved less efficiently than their all-RNA analogues; again however, the DNA-armed ribozyme is more effective than the all-RNA ribozyme against such DNA substrates. These results demonstrate that there are no 2'-hydroxyl groups in the arms of the ribozyme that are required for cleavage; and that the structure of the complex formed by the DNA-armed ribozyme with its substrate is more favourable for cleavage than that formed by the all-RNA ribozyme and its substrate.", "contents": "A ribozyme with DNA in the hybridising arms displays enhanced cleavage ability. Hammerhead ribozymes cleave RNA substrates containing the UX sequence, where X = U, C or A, embedded within sequences which are complementary to the hybridising 'arms' of the ribozyme. In this study we have replaced the RNA in the hybridising arms of the ribozyme with DNA, and the resulting ribozyme is many times more active than its precursor. In turnover-kinetics experiments with a 13-mer RNA substrate, the kcat/Km ratios are 10 and 150 microM-1min-1 for the RNA- and DNA-armed ribozymes, respectively. The effect is due mainly to differences in kcat. In independent experiments where the cleavage step is rate-limiting, the DNA-armed ribozyme cleaves the substrate with a rate constant more than 3 times greater than the all-RNA ribozyme. DNA substrates containing a ribocytidine at the cleavage site have been shown to be cleaved less efficiently than their all-RNA analogues; again however, the DNA-armed ribozyme is more effective than the all-RNA ribozyme against such DNA substrates. These results demonstrate that there are no 2'-hydroxyl groups in the arms of the ribozyme that are required for cleavage; and that the structure of the complex formed by the DNA-armed ribozyme with its substrate is more favourable for cleavage than that formed by the all-RNA ribozyme and its substrate."} {"id": "PMID:1280809", "title": "A Mycoplasma protein homologous to mammalian SRP54 recognizes a highly conserved domain of SRP RNA.", "content": "A protein homologous to SRP54, a subunit of the mammalian signal recognition particle (SRP), was identified in Mycoplasma mycoides. The mycoplasma protein was expressed in E.coli and purified to near homogeneity. It was shown to bind specifically in vitro to a small mycoplasma RNA with structural features related to the RNA component of SRP. These findings provide evidence of a ribonucleoprotein complex in mycoplasma reminiscent of SRP. A part of the RNA was protected from ribonuclease digestion in the presence of the SRP54 homologue. The protected region contains structural elements that have been highly conserved in SRP RNAs during evolution.", "contents": "A Mycoplasma protein homologous to mammalian SRP54 recognizes a highly conserved domain of SRP RNA. A protein homologous to SRP54, a subunit of the mammalian signal recognition particle (SRP), was identified in Mycoplasma mycoides. The mycoplasma protein was expressed in E.coli and purified to near homogeneity. It was shown to bind specifically in vitro to a small mycoplasma RNA with structural features related to the RNA component of SRP. These findings provide evidence of a ribonucleoprotein complex in mycoplasma reminiscent of SRP. A part of the RNA was protected from ribonuclease digestion in the presence of the SRP54 homologue. The protected region contains structural elements that have been highly conserved in SRP RNAs during evolution."} {"id": "PMID:1280810", "title": "RNase D, a reported new activity associated with HIV-1 reverse transcriptase, displays the same cleavage specificity as Escherichia coli RNase III.", "content": "RNase D was recently reported as a new enzymatic activity associated with HIV-1 reverse transcriptase (RT), cleaving RNA at two positions within the double-stranded region of the tRNA primer-viral RNA template complex (Ben-Artzi et al., Proc. Natl. Acad. Sci. USA 89 (1992) 927-931). This would make RNase D a fourth distinct activity of HIV-1 RT, in addition to RNA- and DNA-dependent DNA polymerase and RNase H. Using a specific substrate containing tRNA(Lys,3) hybridized to the primer binding site, we were able to detect the reported RNase D activity in our preparations of recombinant HIV-1 RT. This activity was also present in several active-site mutants of RT, suggesting that it is independent of the RNase H and polymerase functionalities of RT. Furthermore, we found that the cleavage specificity of RNase D is the same as that of RNase III isolated from E.coli. A likely explantation of these results--that the observed RNase D activity is attributable to traces of RNase III contamination--was further strengthened by the finding that the recombinant preparations of HIV-1 RT can specifically cleave a phage T7-derived double-stranded RNA processing signal, which has been used as a model substrate for detection of E.coli RNase III. Moreover, RT purified from an RNase III- strain of E.coli displayed no cleavage of the tRNA primer-RNA template complex.", "contents": "RNase D, a reported new activity associated with HIV-1 reverse transcriptase, displays the same cleavage specificity as Escherichia coli RNase III. RNase D was recently reported as a new enzymatic activity associated with HIV-1 reverse transcriptase (RT), cleaving RNA at two positions within the double-stranded region of the tRNA primer-viral RNA template complex (Ben-Artzi et al., Proc. Natl. Acad. Sci. USA 89 (1992) 927-931). This would make RNase D a fourth distinct activity of HIV-1 RT, in addition to RNA- and DNA-dependent DNA polymerase and RNase H. Using a specific substrate containing tRNA(Lys,3) hybridized to the primer binding site, we were able to detect the reported RNase D activity in our preparations of recombinant HIV-1 RT. This activity was also present in several active-site mutants of RT, suggesting that it is independent of the RNase H and polymerase functionalities of RT. Furthermore, we found that the cleavage specificity of RNase D is the same as that of RNase III isolated from E.coli. A likely explantation of these results--that the observed RNase D activity is attributable to traces of RNase III contamination--was further strengthened by the finding that the recombinant preparations of HIV-1 RT can specifically cleave a phage T7-derived double-stranded RNA processing signal, which has been used as a model substrate for detection of E.coli RNase III. Moreover, RT purified from an RNase III- strain of E.coli displayed no cleavage of the tRNA primer-RNA template complex."} {"id": "PMID:1280817", "title": "Intervention in Graves' disease. Choosing among imperfect but effective treatment options.", "content": "Graves' disease is an autoimmune disorder that comprises the triad of diffuse toxic goiter, ophthalmopathy, and infiltrative dermopathy, although all three are not necessarily present in a given patient. The manifestations of Graves' disease vary, depending on the patient's age and other factors. Choice of therapy is influenced by the patient's age, history of heart disease, pregnancy status, expectations, and preferences. Most patients are treated with either radioactive iodine (sodium iodide I 131 [Iodotope]) or the antithyroid drugs propylthiouracil or methimazole (Tapazole). Antithyroid drugs may be more effective in producing long-term remission if levothyroxine sodium (Levothroid, Levoxine, Synthroid) is added to the regimen after the patient becomes euthyroid. Hypothyroidism occurs in many patients following 131I therapy but is also seen in a substantial number of patients who have been treated with thyroidectomy and even in some who have taken antithyroid drugs. Long-term follow-up is necessary, regardless of type of initial treatment, and should include an annual physical examination and measurement of serum concentrations of thyrotropin and the free thyroxine index, both of which should be maintained in the normal range.", "contents": "Intervention in Graves' disease. Choosing among imperfect but effective treatment options. Graves' disease is an autoimmune disorder that comprises the triad of diffuse toxic goiter, ophthalmopathy, and infiltrative dermopathy, although all three are not necessarily present in a given patient. The manifestations of Graves' disease vary, depending on the patient's age and other factors. Choice of therapy is influenced by the patient's age, history of heart disease, pregnancy status, expectations, and preferences. Most patients are treated with either radioactive iodine (sodium iodide I 131 [Iodotope]) or the antithyroid drugs propylthiouracil or methimazole (Tapazole). Antithyroid drugs may be more effective in producing long-term remission if levothyroxine sodium (Levothroid, Levoxine, Synthroid) is added to the regimen after the patient becomes euthyroid. Hypothyroidism occurs in many patients following 131I therapy but is also seen in a substantial number of patients who have been treated with thyroidectomy and even in some who have taken antithyroid drugs. Long-term follow-up is necessary, regardless of type of initial treatment, and should include an annual physical examination and measurement of serum concentrations of thyrotropin and the free thyroxine index, both of which should be maintained in the normal range."} {"id": "PMID:1280819", "title": "Cloned, expressed rat cerebellar nitric oxide synthase contains stoichiometric amounts of heme, which binds carbon monoxide.", "content": "The endogenous formation of nitric oxide (NO) has become an area of intense interest as evidence for its biological functions has been obtained in three distinct tissues: circulating macrophages, in which it exerts cytotoxic effects; blood vessels, in which it has been identified as endothelium-derived relaxing factor; and neuronal cells, in which it functions as a neurotransmitter. The formation of NO in brain extracts has been shown to be catalyzed by an enzyme, termed NO synthase, which generates the NO responsible for stimulation of cGMP formation, the highest levels of which occur in the cerebellum. NO synthase catalyzes the formation of citrulline from arginine with the coincident production of NO and has been shown to be a flavoprotein, containing 1 mol each of FAD and FMN, tetrahydrobiopterin, and iron. It is also reported to contain an alpha-helical, calmodulin-binding consensus sequence consistent with its stimulation by calmodulin in the presence of Ca2+. The formation of NO requires incorporation of one of the atoms of molecular oxygen into one of the guanidinium nitrogen atoms of arginine with the coincident formation of citrulline. This communication reports that rat cerebellar NO synthase, cloned and stably expressed in human kidney 293 cells, contains heme in amounts stoichiometric with the flavins FAD and FMN as evidenced by the appearance of a pyridine hemochrome and a reduced CO difference spectrum with an absorbance maximum at approximately 445 nm. The finding of a CO-binding heme moiety explains the presence of iron in the enzyme and suggests a role for prosthetic heme as an oxygenase reaction center. This report also presents evidence for incorporation of delta-[14C]aminolevulinate specifically into immunoprecipitable NO synthase in stably transfected human kidney 293 cells but not in nontransfected cells. Simultaneously, K. A. White and M. A. Marletta [(1992) Biochemistry 31, 6627-6631] have demonstrated a CO-binding heme prosthetic group in purified murine macrophage NO synthase and have suggested the identity of these reaction centers in both the constitutive (cerebellar) and inducible (macrophage) forms of NO synthase.", "contents": "Cloned, expressed rat cerebellar nitric oxide synthase contains stoichiometric amounts of heme, which binds carbon monoxide. The endogenous formation of nitric oxide (NO) has become an area of intense interest as evidence for its biological functions has been obtained in three distinct tissues: circulating macrophages, in which it exerts cytotoxic effects; blood vessels, in which it has been identified as endothelium-derived relaxing factor; and neuronal cells, in which it functions as a neurotransmitter. The formation of NO in brain extracts has been shown to be catalyzed by an enzyme, termed NO synthase, which generates the NO responsible for stimulation of cGMP formation, the highest levels of which occur in the cerebellum. NO synthase catalyzes the formation of citrulline from arginine with the coincident production of NO and has been shown to be a flavoprotein, containing 1 mol each of FAD and FMN, tetrahydrobiopterin, and iron. It is also reported to contain an alpha-helical, calmodulin-binding consensus sequence consistent with its stimulation by calmodulin in the presence of Ca2+. The formation of NO requires incorporation of one of the atoms of molecular oxygen into one of the guanidinium nitrogen atoms of arginine with the coincident formation of citrulline. This communication reports that rat cerebellar NO synthase, cloned and stably expressed in human kidney 293 cells, contains heme in amounts stoichiometric with the flavins FAD and FMN as evidenced by the appearance of a pyridine hemochrome and a reduced CO difference spectrum with an absorbance maximum at approximately 445 nm. The finding of a CO-binding heme moiety explains the presence of iron in the enzyme and suggests a role for prosthetic heme as an oxygenase reaction center. This report also presents evidence for incorporation of delta-[14C]aminolevulinate specifically into immunoprecipitable NO synthase in stably transfected human kidney 293 cells but not in nontransfected cells. Simultaneously, K. A. White and M. A. Marletta [(1992) Biochemistry 31, 6627-6631] have demonstrated a CO-binding heme prosthetic group in purified murine macrophage NO synthase and have suggested the identity of these reaction centers in both the constitutive (cerebellar) and inducible (macrophage) forms of NO synthase."} {"id": "PMID:1280820", "title": "Identification of a pathogenic epitope involved in initiation of Heymann nephritis.", "content": "Heymann nephritis is an experimental autoimmune disease model for human membranous nephropathy. We have recently identified a pathogenic epitope, clone 14 (C14), responsible for formation and deposition of glomerular immune complexes that is contained within the small subunit of the Heymann nephritis antigenic complex (HNAC). HNAC is a heterodimer composed of a large subunit designated gp330 and a smaller (44 kDa) subunit, which is immunologically identical to the receptor-associated protein. In this study, we prepared antibodies to fusion proteins with C-terminal deletions in the C14 sequence and assessed their ability to promote formation of immune deposits (IDs). When IgG specific for the shortest truncated fusion protein (C14/delta 3; 86 amino acids) was injected into rats, small IDs developed. In contrast, when IgG raised against the full-length C14 sequence was depleted of its reactivity toward the C14/delta 3 fusion protein (C14/delta 3-fp), no IDs could be detected. These data indicate that at least one pathogenic epitope is contained within the N-terminal 86 amino acids of C14. Since the IDs induced with the C14/delta 3-fp-specific IgG are smaller than those induced with the poly-epitope-specific anti-gp330 antibodies, it is likely that other epitopes in addition to those expressed by the C14/delta 3-fp are required for formation and growth of immune complexes.", "contents": "Identification of a pathogenic epitope involved in initiation of Heymann nephritis. Heymann nephritis is an experimental autoimmune disease model for human membranous nephropathy. We have recently identified a pathogenic epitope, clone 14 (C14), responsible for formation and deposition of glomerular immune complexes that is contained within the small subunit of the Heymann nephritis antigenic complex (HNAC). HNAC is a heterodimer composed of a large subunit designated gp330 and a smaller (44 kDa) subunit, which is immunologically identical to the receptor-associated protein. In this study, we prepared antibodies to fusion proteins with C-terminal deletions in the C14 sequence and assessed their ability to promote formation of immune deposits (IDs). When IgG specific for the shortest truncated fusion protein (C14/delta 3; 86 amino acids) was injected into rats, small IDs developed. In contrast, when IgG raised against the full-length C14 sequence was depleted of its reactivity toward the C14/delta 3 fusion protein (C14/delta 3-fp), no IDs could be detected. These data indicate that at least one pathogenic epitope is contained within the N-terminal 86 amino acids of C14. Since the IDs induced with the C14/delta 3-fp-specific IgG are smaller than those induced with the poly-epitope-specific anti-gp330 antibodies, it is likely that other epitopes in addition to those expressed by the C14/delta 3-fp are required for formation and growth of immune complexes."} {"id": "PMID:1280821", "title": "itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2.", "content": "T lymphocytes are activated by interactions with antigens, lymphokines, and cell adhesion molecules. Tyrosine phosphorylation has been implicated as important in signaling through each of these pathways, but except for p56lck, a member of the Src family that associates with CD4 and CD8, the protein-tyrosine kinases involved have not been defined. We describe here a tyrosine kinase gene that we have designated itk (for IL-2-inducible T-cell kinase). The itk gene specifies a 72-kDa protein-tyrosine kinase that is related to members of the Src family but lacks two features characteristic of Src kinases: an N-terminal myristoylation consensus sequence and a regulatory tyrosine residue near the C terminus. Analysis of mouse tissues and cell lines indicates that itk is specifically expressed in the T-cell lineage, suggesting that the tyrosine kinase encoded by itk functions in a signal transduction pathway unique to T lymphocytes. On addition of IL-2 to responsive T cells, itk RNA increases in parallel with that of IL-2R alpha, implicating itk in T-cell activation.", "contents": "itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2. T lymphocytes are activated by interactions with antigens, lymphokines, and cell adhesion molecules. Tyrosine phosphorylation has been implicated as important in signaling through each of these pathways, but except for p56lck, a member of the Src family that associates with CD4 and CD8, the protein-tyrosine kinases involved have not been defined. We describe here a tyrosine kinase gene that we have designated itk (for IL-2-inducible T-cell kinase). The itk gene specifies a 72-kDa protein-tyrosine kinase that is related to members of the Src family but lacks two features characteristic of Src kinases: an N-terminal myristoylation consensus sequence and a regulatory tyrosine residue near the C terminus. Analysis of mouse tissues and cell lines indicates that itk is specifically expressed in the T-cell lineage, suggesting that the tyrosine kinase encoded by itk functions in a signal transduction pathway unique to T lymphocytes. On addition of IL-2 to responsive T cells, itk RNA increases in parallel with that of IL-2R alpha, implicating itk in T-cell activation."} {"id": "PMID:1280822", "title": "Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2, and NK3 tachykinin receptors.", "content": "Using a sensitive in vitro microperfusion method, the effects of selective and potent agonists of NK1, NK2, and NK3 tachykinin receptors ([Pro9]SP, ([Lys5,MeLeu9,Nle10]NKA-(4-10), and [Pro7]NKB, respectively) on the presynaptic control of dopamine release were investigated in striosomal-enriched (area rich in [3H]naloxone binding sites) and matrix-enriched areas of the rat striatum. Marked differences could be demonstrated as follows: (i) when used at 0.1 microM, the NK1 agonist stimulated the release of [3H]dopamine continuously synthesized from [3H]tyrosine in both compartments, while the NK2 and NK3 agonists enhanced the release of [3H]dopamine only in the matrix; (ii) the stimulatory effect of the NK3 agonist was less pronounced than those of the NK1 and NK2 agonists; (iii) the NK1 agonist-evoked responses were tetrodotoxin (1 microM) sensitive, while those of the NK2 and NK3 agonists were, respectively, partially and totally tetrodotoxin resistant; (iv) specific receptors are involved in these responses since the stimulatory effects of the NK1 and NK2 agonists were, respectively, blocked by potent antagonists of NK1 (RP-67580; 1 microM) and NK2 (SR-48968; 1 microM) receptors, while these antagonists did not affect the NK3 agonist-evoked response; (v) the indirect stimulatory effect of the NK1 agonist was partially reduced under local blockade of cholinergic transmission in the matrix but not in the striosomal-enriched area. Interestingly, this study also revealed mismatches between autoradiographic data and receptor-mediated responses, since NK2 binding sites could not be observed in the striatum while NK3 but not NK1 binding sites were visualized in the striosomal-enriched area.", "contents": "Distinct presynaptic control of dopamine release in striosomal- and matrix-enriched areas of the rat striatum by selective agonists of NK1, NK2, and NK3 tachykinin receptors. Using a sensitive in vitro microperfusion method, the effects of selective and potent agonists of NK1, NK2, and NK3 tachykinin receptors ([Pro9]SP, ([Lys5,MeLeu9,Nle10]NKA-(4-10), and [Pro7]NKB, respectively) on the presynaptic control of dopamine release were investigated in striosomal-enriched (area rich in [3H]naloxone binding sites) and matrix-enriched areas of the rat striatum. Marked differences could be demonstrated as follows: (i) when used at 0.1 microM, the NK1 agonist stimulated the release of [3H]dopamine continuously synthesized from [3H]tyrosine in both compartments, while the NK2 and NK3 agonists enhanced the release of [3H]dopamine only in the matrix; (ii) the stimulatory effect of the NK3 agonist was less pronounced than those of the NK1 and NK2 agonists; (iii) the NK1 agonist-evoked responses were tetrodotoxin (1 microM) sensitive, while those of the NK2 and NK3 agonists were, respectively, partially and totally tetrodotoxin resistant; (iv) specific receptors are involved in these responses since the stimulatory effects of the NK1 and NK2 agonists were, respectively, blocked by potent antagonists of NK1 (RP-67580; 1 microM) and NK2 (SR-48968; 1 microM) receptors, while these antagonists did not affect the NK3 agonist-evoked response; (v) the indirect stimulatory effect of the NK1 agonist was partially reduced under local blockade of cholinergic transmission in the matrix but not in the striosomal-enriched area. Interestingly, this study also revealed mismatches between autoradiographic data and receptor-mediated responses, since NK2 binding sites could not be observed in the striatum while NK3 but not NK1 binding sites were visualized in the striosomal-enriched area."} {"id": "PMID:1280823", "title": "Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew.", "content": "src homology 2 (SH2) domains direct binding to specific phosphotyrosyl proteins. Recently, SH2-containing protein-tyrosine-phosphatases (PTPs) were identified. Using degenerate oligonucleotides and the PCR, we have cloned a cDNA for an additional PTP, SH-PTP2, which contains two SH2 domains and is expressed ubiquitously. When expressed in Escherichia coli, SH-PTP2 displays tyrosine-specific phosphatase activity. Strong sequence similarity between SH-PTP2 and the Drosophila gene corkscrew (csw) and their similar patterns of expression suggest that SH-PTP2 is the human corkscrew homolog. Sequence comparisons between SH-PTP2, SH-PTP1, corkscrew, and other SH2-containing proteins suggest the existence of a subfamily of SH2 domains found specifically in PTPs, whereas comparison of the PTP domains of the SH2-containing PTPs with other tyrosine phosphatases suggests the existence of a subfamily of PTPs containing SH2 domains. Since corkscrew, a member of the terminal class signal transduction pathway, acts in concert with D-raf to positively transduce the signal generated by the receptor tyrosine kinase torso, these findings suggest several mechanisms by which SH-PTP2 may participate in mammalian signal transduction.", "contents": "Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew. src homology 2 (SH2) domains direct binding to specific phosphotyrosyl proteins. Recently, SH2-containing protein-tyrosine-phosphatases (PTPs) were identified. Using degenerate oligonucleotides and the PCR, we have cloned a cDNA for an additional PTP, SH-PTP2, which contains two SH2 domains and is expressed ubiquitously. When expressed in Escherichia coli, SH-PTP2 displays tyrosine-specific phosphatase activity. Strong sequence similarity between SH-PTP2 and the Drosophila gene corkscrew (csw) and their similar patterns of expression suggest that SH-PTP2 is the human corkscrew homolog. Sequence comparisons between SH-PTP2, SH-PTP1, corkscrew, and other SH2-containing proteins suggest the existence of a subfamily of SH2 domains found specifically in PTPs, whereas comparison of the PTP domains of the SH2-containing PTPs with other tyrosine phosphatases suggests the existence of a subfamily of PTPs containing SH2 domains. Since corkscrew, a member of the terminal class signal transduction pathway, acts in concert with D-raf to positively transduce the signal generated by the receptor tyrosine kinase torso, these findings suggest several mechanisms by which SH-PTP2 may participate in mammalian signal transduction."} {"id": "PMID:1280824", "title": "Tyrosine phosphorylation is required for activation of an alpha interferon-stimulated transcription factor.", "content": "The signal transduction pathway of alpha interferon utilizes tyrosine phosphorylation to transmit a signal generated at the cell surface to the transcriptional machinery in the nucleus. Activation of the interferon pathway initiates with the binding of alpha interferon to its cell surface receptor. The ligand-receptor complex signals the activation of a latent cytoplasmic transcription factor. The active form of the interferon-stimulated gene factor (ISGF3) is phosphorylated on tyrosine residues. ISGF3 subsequently translocates to the nucleus and binds to a DNA sequence, the interferon-stimulated response element, found within the promoter of inducible genes. ISGF3 is a multicomponent factor consisting of four proteins of 113 kDa, 91 kDa, 84 kDa, and 48 kDa. Three proteins consistent with sizes of 113 kDa, 91 kDa, and 84 kDa copurify with ISGF3 and are phosphorylated on tyrosine residues after stimulation by alpha interferon. Tyrosine phosphorylation is essential for activation of ISGF3. Genistein, a tyrosine kinase inhibitor, blocks the appearance of ISGF3 and blocks the transcriptional stimulation of interferon-induced genes. This study shows that tyrosine phosphorylation provides a link between the interferon-receptor complex at the plasma membrane and specific activation of gene expression in the nucleus.", "contents": "Tyrosine phosphorylation is required for activation of an alpha interferon-stimulated transcription factor. The signal transduction pathway of alpha interferon utilizes tyrosine phosphorylation to transmit a signal generated at the cell surface to the transcriptional machinery in the nucleus. Activation of the interferon pathway initiates with the binding of alpha interferon to its cell surface receptor. The ligand-receptor complex signals the activation of a latent cytoplasmic transcription factor. The active form of the interferon-stimulated gene factor (ISGF3) is phosphorylated on tyrosine residues. ISGF3 subsequently translocates to the nucleus and binds to a DNA sequence, the interferon-stimulated response element, found within the promoter of inducible genes. ISGF3 is a multicomponent factor consisting of four proteins of 113 kDa, 91 kDa, 84 kDa, and 48 kDa. Three proteins consistent with sizes of 113 kDa, 91 kDa, and 84 kDa copurify with ISGF3 and are phosphorylated on tyrosine residues after stimulation by alpha interferon. Tyrosine phosphorylation is essential for activation of ISGF3. Genistein, a tyrosine kinase inhibitor, blocks the appearance of ISGF3 and blocks the transcriptional stimulation of interferon-induced genes. This study shows that tyrosine phosphorylation provides a link between the interferon-receptor complex at the plasma membrane and specific activation of gene expression in the nucleus."} {"id": "PMID:1280825", "title": "Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues.", "content": "The ability of lymphocytes to recognize and bind to high endothelial venules (HEVs) is essential for lymphocyte migration from the blood into lymphoid tissues and into sites of inflammation. Endothelial cell binding capacity also critically determines the clinical usefulness of T-cell lines and clones in immunotherapy. In the present study, interleukin-2-dependent T-cell lines were derived from the blood, lamina propria of the gut, inflamed synovium, synovial fluid, and peripheral lymph nodes. After 3-8 weeks of culture, the expression of homing-associated molecules and binding to mucosal, synovial, and peripheral lymph node HEVs were analyzed. Cell lines derived from the blood and mucosal sites bound significantly better to mucosal and synovial HEVs than to peripheral lymph node HEVs. Three out of seven synovial T-cell lines showed preferential binding to synovial HEVs, whereas the rest bound almost equally well to synovial and mucosal HEVs. T-cell lines from peripheral lymph nodes bound preferentially to lymph node HEVs despite the lack of L-selectin (the peripheral lymph node homing receptor). Expression of the known homing-associated molecules did not predict the HEV-binding specificity of these lines. Importantly, two cell lines bound well to synovial venules, but poorly, if at all, to mucosal or peripheral lymph node HEVs, supporting the concept that synovial-specific HEV recognition mechanisms exist. In conclusion, the tissue origin of T-cell lines critically determines their selectivity for endothelial cell recognition, and besides the known \"homing receptors,\" other molecules may also mediate tissue-specific HEV-binding of interleukin-2-activated T cells.", "contents": "Selective endothelial binding of interleukin-2-dependent human T-cell lines derived from different tissues. The ability of lymphocytes to recognize and bind to high endothelial venules (HEVs) is essential for lymphocyte migration from the blood into lymphoid tissues and into sites of inflammation. Endothelial cell binding capacity also critically determines the clinical usefulness of T-cell lines and clones in immunotherapy. In the present study, interleukin-2-dependent T-cell lines were derived from the blood, lamina propria of the gut, inflamed synovium, synovial fluid, and peripheral lymph nodes. After 3-8 weeks of culture, the expression of homing-associated molecules and binding to mucosal, synovial, and peripheral lymph node HEVs were analyzed. Cell lines derived from the blood and mucosal sites bound significantly better to mucosal and synovial HEVs than to peripheral lymph node HEVs. Three out of seven synovial T-cell lines showed preferential binding to synovial HEVs, whereas the rest bound almost equally well to synovial and mucosal HEVs. T-cell lines from peripheral lymph nodes bound preferentially to lymph node HEVs despite the lack of L-selectin (the peripheral lymph node homing receptor). Expression of the known homing-associated molecules did not predict the HEV-binding specificity of these lines. Importantly, two cell lines bound well to synovial venules, but poorly, if at all, to mucosal or peripheral lymph node HEVs, supporting the concept that synovial-specific HEV recognition mechanisms exist. In conclusion, the tissue origin of T-cell lines critically determines their selectivity for endothelial cell recognition, and besides the known \"homing receptors,\" other molecules may also mediate tissue-specific HEV-binding of interleukin-2-activated T cells."} {"id": "PMID:1280826", "title": "Transmembrane signaling by the high-affinity IgE receptor on membrane preparations.", "content": "Aggregating the receptor with high affinity for IgE (Fc epsilon RI) stimulates a variety of phenomena in mast cells. Previous efforts to reproduce some of these events in broken-cell preparations such as isolated membranes have had limited success, possibly because the phenomena being monitored were too distal from the initial events. One of the earliest responses is now known to be the phosphorylation of tyrosine residues on several proteins, including the beta and gamma subunits of Fc epsilon RI. We show that in cell sonicates or on partially purified membranes derived from tumor mast cells, aggregating Fc epsilon RI stimulates phosphorylation of receptor tyrosine residues. As in the intact cells, receptor-mediated phosphorylation occurs only on receptors that are themselves aggregated. Because even in the unfractionated sonicates the phosphorylation of other cellular components was not detectably enhanced, and because the evidence is against the receptor itself being a kinase, our results suggest that phosphorylation of Fc epsilon RI is one of the earliest events stimulated by the receptor--an event that can now be investigated on simpler biological preparations than previously available.", "contents": "Transmembrane signaling by the high-affinity IgE receptor on membrane preparations. Aggregating the receptor with high affinity for IgE (Fc epsilon RI) stimulates a variety of phenomena in mast cells. Previous efforts to reproduce some of these events in broken-cell preparations such as isolated membranes have had limited success, possibly because the phenomena being monitored were too distal from the initial events. One of the earliest responses is now known to be the phosphorylation of tyrosine residues on several proteins, including the beta and gamma subunits of Fc epsilon RI. We show that in cell sonicates or on partially purified membranes derived from tumor mast cells, aggregating Fc epsilon RI stimulates phosphorylation of receptor tyrosine residues. As in the intact cells, receptor-mediated phosphorylation occurs only on receptors that are themselves aggregated. Because even in the unfractionated sonicates the phosphorylation of other cellular components was not detectably enhanced, and because the evidence is against the receptor itself being a kinase, our results suggest that phosphorylation of Fc epsilon RI is one of the earliest events stimulated by the receptor--an event that can now be investigated on simpler biological preparations than previously available."} {"id": "PMID:1280827", "title": "DNA binding and heteromerization of the Drosophila transcription factor chorion factor 1/ultraspiracle.", "content": "The Drosophila chorion factor 1/ultraspiracle (CF1/USP) transcription factor, a homologue of the retinoid X receptor, is a developmentally important member of the family of nuclear (steroid) hormone receptors. Using newly developed monoclonal antibodies and a full-length bacterially produced protein, we have studied in detail the in vitro DNA-binding properties of this factor and aspects of its distribution in vivo. During oogenesis, CF1/USP is present both in germline cells and in the somatic follicular epithelium. We have determined the optimal binding site of partially purified bacterially produced CF1/USP by an in vitro selection procedure and also have characterized its binding to the follicular-specific chorion s15 promoter. In vitro this bacterially produced factor is unusual in binding to a single element (\"half-site\"); simultaneous but noncoordinate binding to a second half-site is possible if these repeated elements are organized in direct orientation and spaced adequately. However, the factor interacts synergistically with several other nuclear hormone receptors: notably, it can form in vitro heteromers with mammalian thyroid and retinoic acid receptors, binding to two half-sites that are organized in either direct or inverted orientation. In vivo the factor most probably functions as a heterodimer, but its partner(s) remains to be determined.", "contents": "DNA binding and heteromerization of the Drosophila transcription factor chorion factor 1/ultraspiracle. The Drosophila chorion factor 1/ultraspiracle (CF1/USP) transcription factor, a homologue of the retinoid X receptor, is a developmentally important member of the family of nuclear (steroid) hormone receptors. Using newly developed monoclonal antibodies and a full-length bacterially produced protein, we have studied in detail the in vitro DNA-binding properties of this factor and aspects of its distribution in vivo. During oogenesis, CF1/USP is present both in germline cells and in the somatic follicular epithelium. We have determined the optimal binding site of partially purified bacterially produced CF1/USP by an in vitro selection procedure and also have characterized its binding to the follicular-specific chorion s15 promoter. In vitro this bacterially produced factor is unusual in binding to a single element (\"half-site\"); simultaneous but noncoordinate binding to a second half-site is possible if these repeated elements are organized in direct orientation and spaced adequately. However, the factor interacts synergistically with several other nuclear hormone receptors: notably, it can form in vitro heteromers with mammalian thyroid and retinoic acid receptors, binding to two half-sites that are organized in either direct or inverted orientation. In vivo the factor most probably functions as a heterodimer, but its partner(s) remains to be determined."} {"id": "PMID:1280828", "title": "Distinct monoclonal antibodies separately label the hexons or the pentons of herpes simplex virus capsid.", "content": "The surface shell of the capsid of herpes simplex virus type 1 (HSV-1) is 15 nm thick and 125 nm in outer diameter and has the form of an icosahedral (T = 16) surface lattice, composed of 150 hexons and 12 pentons. Hexons are traversed by axial channels and have six-fold symmetric external protrusions, separated by triangular nodules (\"triplexes\"). Pentons resemble hexons morphologically, apart from their different order of symmetry. To localize VP5, the major capsid protein, in the shell structure and to investigate whether pentons are composed of the same molecules as hexons, we have performed cryo-electron microscopy and three-dimensional image reconstructions of control HSV-1 B capsids and of B capsids immunoprecipitated with two monoclonal antibodies raised against purified VP5 and purified capsids. The results clearly map the epitope of the anti-VP5 monoclonal antibody to the distal tips of the hexon protrusions. In contrast, no detectable labeling of pentons was observed. We conclude that the hexon protrusions are domains of VP5 hexamers, other parts of these molecules forming the basic matrix of the capsid shell to which the other proteins are attached at specific sites. Conversely, the anti-capsid monoclonal antibody decorates the outer rim of pentons but does not bind to hexons. These observations imply that either pentons are composed of some other protein(s) or that they also contain VP5, but in a conformation sufficiently different from that assumed in hexons as to transform its antigenic character. Other evidence leads us to favor the latter alternative.", "contents": "Distinct monoclonal antibodies separately label the hexons or the pentons of herpes simplex virus capsid. The surface shell of the capsid of herpes simplex virus type 1 (HSV-1) is 15 nm thick and 125 nm in outer diameter and has the form of an icosahedral (T = 16) surface lattice, composed of 150 hexons and 12 pentons. Hexons are traversed by axial channels and have six-fold symmetric external protrusions, separated by triangular nodules (\"triplexes\"). Pentons resemble hexons morphologically, apart from their different order of symmetry. To localize VP5, the major capsid protein, in the shell structure and to investigate whether pentons are composed of the same molecules as hexons, we have performed cryo-electron microscopy and three-dimensional image reconstructions of control HSV-1 B capsids and of B capsids immunoprecipitated with two monoclonal antibodies raised against purified VP5 and purified capsids. The results clearly map the epitope of the anti-VP5 monoclonal antibody to the distal tips of the hexon protrusions. In contrast, no detectable labeling of pentons was observed. We conclude that the hexon protrusions are domains of VP5 hexamers, other parts of these molecules forming the basic matrix of the capsid shell to which the other proteins are attached at specific sites. Conversely, the anti-capsid monoclonal antibody decorates the outer rim of pentons but does not bind to hexons. These observations imply that either pentons are composed of some other protein(s) or that they also contain VP5, but in a conformation sufficiently different from that assumed in hexons as to transform its antigenic character. Other evidence leads us to favor the latter alternative."} {"id": "PMID:1280829", "title": "Nitric oxide mediates norepinephrine-induced prostaglandin E2 release from the hypothalamus.", "content": "Nitric oxide (NO), formed by conversion of arginine to citrulline and NO by NO synthase, mediates relaxation of vascular smooth muscle. NO synthase has been demonstrated by immunocytochemical methods in neurons in various parts of the central nervous system including the hypothalamus. The latter finding suggested to us that NO might play a role in controlling the release of hypothalamic peptides. We have previously shown that norepinephrine mediates the release of luteinizing hormone-releasing hormone (LHRH) from LHRH terminals in the median eminence into the hypophyseal portal veins, which transport LHRH to the anterior pituitary gland to trigger release of luteinizing hormone from gonadotrophs. LHRH release from these terminals requires increased release of prostaglandin E2 (PGE2). PGE2 activates adenylate cyclase to produce cAMP, and then cAMP induces the exocytosis of LHRH secretory granules. In view of the evidence above and because of the developing evidence for the importance of NO in the central nervous system, it occurred to us that NO might be involved in this process. Consequently, we evaluated the role of NO in the release of PGE2 from medial basal hypothalamic fragments. As previously reported, norepinephrine (10 microM) increased PGE2 release from the hypothalamic fragments. The inhibitor of NO synthase NG-monomethyl-L-arginine (NMMA, 300 microM) blocked the stimulation of PGE2 release induced by norepinephrine but had no effect on the basal release of PGE2. Sodium nitroprusside (100 microM), which liberates NO, also elevated PGE2 release from the hypothalamic fragments. This elevation was not affected by NMMA, presumably because NMMA blocks enzymatic generation of NO but does not alter NO liberated by nitroprusside. When the NO liberated by nitroprusside was inactivated by hemoglobin (2 micrograms/ml), the effect of nitroprusside on PGE2 release was completely inhibited. Neither NMMA nor hemoglobin altered the basal release of PGE2, which indicates that NO is not responsible for basal PGE2 release. Addition of L-arginine (10 microM to 1 mM), the substrate for NO synthase, had no effect on basal PGE2 production. These results indicate that NO synthase is not activated in unstimulated hypothalamic fragments in vitro. The results suggest that norepinephrine activates NO synthase leading to the production of NO, which subsequently activates cyclooxygenase and results in the production of PGE2. PGE2 then activates adenylate cyclase leading to generation of increased cAMP, which induces exocytosis of secretory granules of LHRH and other neuropeptides released by PGE2. The indication that NO is essential to norepinephrine-induced release of PGE2 from hypothalamic fragments provides insight into the mechanism of LHRH release and the results open the possibility that the importance of NO to neuronal functions may be widespread in the nervous system.", "contents": "Nitric oxide mediates norepinephrine-induced prostaglandin E2 release from the hypothalamus. Nitric oxide (NO), formed by conversion of arginine to citrulline and NO by NO synthase, mediates relaxation of vascular smooth muscle. NO synthase has been demonstrated by immunocytochemical methods in neurons in various parts of the central nervous system including the hypothalamus. The latter finding suggested to us that NO might play a role in controlling the release of hypothalamic peptides. We have previously shown that norepinephrine mediates the release of luteinizing hormone-releasing hormone (LHRH) from LHRH terminals in the median eminence into the hypophyseal portal veins, which transport LHRH to the anterior pituitary gland to trigger release of luteinizing hormone from gonadotrophs. LHRH release from these terminals requires increased release of prostaglandin E2 (PGE2). PGE2 activates adenylate cyclase to produce cAMP, and then cAMP induces the exocytosis of LHRH secretory granules. In view of the evidence above and because of the developing evidence for the importance of NO in the central nervous system, it occurred to us that NO might be involved in this process. Consequently, we evaluated the role of NO in the release of PGE2 from medial basal hypothalamic fragments. As previously reported, norepinephrine (10 microM) increased PGE2 release from the hypothalamic fragments. The inhibitor of NO synthase NG-monomethyl-L-arginine (NMMA, 300 microM) blocked the stimulation of PGE2 release induced by norepinephrine but had no effect on the basal release of PGE2. Sodium nitroprusside (100 microM), which liberates NO, also elevated PGE2 release from the hypothalamic fragments. This elevation was not affected by NMMA, presumably because NMMA blocks enzymatic generation of NO but does not alter NO liberated by nitroprusside. When the NO liberated by nitroprusside was inactivated by hemoglobin (2 micrograms/ml), the effect of nitroprusside on PGE2 release was completely inhibited. Neither NMMA nor hemoglobin altered the basal release of PGE2, which indicates that NO is not responsible for basal PGE2 release. Addition of L-arginine (10 microM to 1 mM), the substrate for NO synthase, had no effect on basal PGE2 production. These results indicate that NO synthase is not activated in unstimulated hypothalamic fragments in vitro. The results suggest that norepinephrine activates NO synthase leading to the production of NO, which subsequently activates cyclooxygenase and results in the production of PGE2. PGE2 then activates adenylate cyclase leading to generation of increased cAMP, which induces exocytosis of secretory granules of LHRH and other neuropeptides released by PGE2. The indication that NO is essential to norepinephrine-induced release of PGE2 from hypothalamic fragments provides insight into the mechanism of LHRH release and the results open the possibility that the importance of NO to neuronal functions may be widespread in the nervous system."} {"id": "PMID:1280830", "title": "A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis.", "content": "We recently found that scatter factor (SF), a cell motility factor with a multimodular structure, is identical to hepatocyte growth factor (HGF), a potent mitogen of various cell types. SF/HGF is the ligand of the c-Met receptor tyrosine kinase. Here we used transient expression of naturally occurring and in vitro mutagenized cDNAs of SF/HGF to delineate the protein domains necessary for biological activity and binding to the c-Met receptor. (i) A single-chain SF/HGF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg-494--> Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A SF/HGF splice variant encoding a protein with a 5-amino acid deletion in the first kringle domain was as highly active as the wild-type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N terminus and the first two kringle domains bound the c-Met receptor, stimulated tyrosine auto-phosphorylation, and induced scattering of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N terminus/first two kringle regions of SF/HGF is sufficient for binding to the Met receptor and that this leads to the activation of the downstream signal cascade involved in the motility response. However, the complete SF/HGF protein seems to be required for mitogenic activity.", "contents": "A functional domain in the heavy chain of scatter factor/hepatocyte growth factor binds the c-Met receptor and induces cell dissociation but not mitogenesis. We recently found that scatter factor (SF), a cell motility factor with a multimodular structure, is identical to hepatocyte growth factor (HGF), a potent mitogen of various cell types. SF/HGF is the ligand of the c-Met receptor tyrosine kinase. Here we used transient expression of naturally occurring and in vitro mutagenized cDNAs of SF/HGF to delineate the protein domains necessary for biological activity and binding to the c-Met receptor. (i) A single-chain SF/HGF resulting from the destruction of the protease cleavage site between heavy and light chain (Arg-494--> Gln) was largely inactive, indicating that proteolytic cleavage is essential for acquisition of the biologically active conformation. (ii) A SF/HGF splice variant encoding a protein with a 5-amino acid deletion in the first kringle domain was as highly active as the wild-type molecule. (iii) The separately expressed light chain (with serine protease homology) was inactive in all assays tested. (iv) The separate heavy chain as well as a naturally occurring splice variant consisting of the N terminus and the first two kringle domains bound the c-Met receptor, stimulated tyrosine auto-phosphorylation, and induced scattering of epithelial cells but not mitogenesis. These data indicate that a functional domain in the N terminus/first two kringle regions of SF/HGF is sufficient for binding to the Met receptor and that this leads to the activation of the downstream signal cascade involved in the motility response. However, the complete SF/HGF protein seems to be required for mitogenic activity."} {"id": "PMID:1280831", "title": "Genetic control of murine hematopoietic stem cell pool sizes and cycling kinetics.", "content": "Bone marrow from each of two inbred mouse strains, C57BL/6J and DBA/2J, was highly enriched for stem cells using flow cytometry and was divided into two stem cell subpopulations using the mitochondrial dye rhodamine 123 (Rh-123). The Rh-123lo population was determined to be more primitive than Rh-123hi based on the expression of stem cell markers such as the c-kit protooncogene (stem cell factor receptor) and the Ly-6A/E stem cell antigen (Sca-1) as well as the lack of in vitro colony-forming ability. Compared to DBA/2J mice, marrow from the C57BL/6J strain consistently showed a higher proportion of \"very primitive\" (Rh-123lo) cells, suggesting that the sizes of functionally distinct stem cell subpopulations are maintained under precise genetic control. Marrow from both strains exposed to the cytotoxic drug 5-fluorouracil showed a dramatic increase in the proportion of Rh-123lo cells within 2 days as repopulation began. Marrow subpopulations returned to pretreatment proportions by the eighth day in DBA/2J mice but not until 14 days in C57BL/6J mice. This intrinsic difference in 5-fluorouracil recovery time was attributed to an increase rate of stem cell cycling in DBA/2J relative to C57BL/6J mice. When stem cell factor was injected into a C57BL/6J<-->DBA/2J allophenic mouse, blood cell chimerism shifted markedly but transiently toward the DBA/2J genotype, suggesting that the DBA/2J target population, because of an inherent kinetic advantage, was able to respond faster to the cytokine. A model is proposed that is based on these and our earlier observations to explain this strain-specific stem cell behavior and offer new insights into the genetic control of stem cell cycling and population dynamics.", "contents": "Genetic control of murine hematopoietic stem cell pool sizes and cycling kinetics. Bone marrow from each of two inbred mouse strains, C57BL/6J and DBA/2J, was highly enriched for stem cells using flow cytometry and was divided into two stem cell subpopulations using the mitochondrial dye rhodamine 123 (Rh-123). The Rh-123lo population was determined to be more primitive than Rh-123hi based on the expression of stem cell markers such as the c-kit protooncogene (stem cell factor receptor) and the Ly-6A/E stem cell antigen (Sca-1) as well as the lack of in vitro colony-forming ability. Compared to DBA/2J mice, marrow from the C57BL/6J strain consistently showed a higher proportion of \"very primitive\" (Rh-123lo) cells, suggesting that the sizes of functionally distinct stem cell subpopulations are maintained under precise genetic control. Marrow from both strains exposed to the cytotoxic drug 5-fluorouracil showed a dramatic increase in the proportion of Rh-123lo cells within 2 days as repopulation began. Marrow subpopulations returned to pretreatment proportions by the eighth day in DBA/2J mice but not until 14 days in C57BL/6J mice. This intrinsic difference in 5-fluorouracil recovery time was attributed to an increase rate of stem cell cycling in DBA/2J relative to C57BL/6J mice. When stem cell factor was injected into a C57BL/6J<-->DBA/2J allophenic mouse, blood cell chimerism shifted markedly but transiently toward the DBA/2J genotype, suggesting that the DBA/2J target population, because of an inherent kinetic advantage, was able to respond faster to the cytokine. A model is proposed that is based on these and our earlier observations to explain this strain-specific stem cell behavior and offer new insights into the genetic control of stem cell cycling and population dynamics."} {"id": "PMID:1280832", "title": "Marked increase in nitric oxide synthase mRNA in rat dorsal root ganglia after peripheral axotomy: in situ hybridization and functional studies.", "content": "Using in situ hybridization, we studied nitric oxide (NO) synthase (EC 1.14.23.-) mRNA in lumbar dorsal root ganglia after peripheral transection of the sciatic nerve in rats. The effect of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester on the nociceptive flexor reflex was also studied in axotomized rats. Nerve section induced a dramatic increase in number of NO synthase mRNA-positive cells in the ipsilateral dorsal root ganglia. In some of these cells the peptides galanin and/or vasoactive intestinal polypeptide and/or neuropeptide Y were also strongly up-regulated. Intravenous administration of nitro-L-arginine methyl ester blocked spinal hyperexcitability at much lower dosages in axotomized than in normal animals. The results suggest involvement of NO in the function of lumbar sensory neurons, especially after axotomy, perhaps preferentially at peripheral sites.", "contents": "Marked increase in nitric oxide synthase mRNA in rat dorsal root ganglia after peripheral axotomy: in situ hybridization and functional studies. Using in situ hybridization, we studied nitric oxide (NO) synthase (EC 1.14.23.-) mRNA in lumbar dorsal root ganglia after peripheral transection of the sciatic nerve in rats. The effect of the NO synthase inhibitor N omega-nitro-L-arginine methyl ester on the nociceptive flexor reflex was also studied in axotomized rats. Nerve section induced a dramatic increase in number of NO synthase mRNA-positive cells in the ipsilateral dorsal root ganglia. In some of these cells the peptides galanin and/or vasoactive intestinal polypeptide and/or neuropeptide Y were also strongly up-regulated. Intravenous administration of nitro-L-arginine methyl ester blocked spinal hyperexcitability at much lower dosages in axotomized than in normal animals. The results suggest involvement of NO in the function of lumbar sensory neurons, especially after axotomy, perhaps preferentially at peripheral sites."} {"id": "PMID:1280833", "title": "Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor.", "content": "Rabbits were immunized with a synthetic phosphopeptide corresponding to a major autophosphorylation site of p185neu/erbB2 to determine the feasibility of producing tyrosine-phosphopeptide-specific antibodies. A series of adsorption and affinity chromatography steps were used to select antibodies with the desired reactivity. Immunoblot experiments showed that the resulting serum is highly specific for tyrosine-phosphorylated forms of p185 and the related epidermal growth factor receptor. The serum recognized these two receptors selectively when compared to five other receptor tyrosine kinases and several phosphorylated substrates. The serum is compatible with tissue-based assays since it detected tyrosine phosphorylation of the epidermal growth factor receptor in immunofluorescence experiments on permeabilized cells. The generality of the procedures used means that similar anti-tyrosine phosphopeptide sera can be produced that recognize other tyrosine kinases and substrates. Such sera will have numerous applications in research and clinical settings.", "contents": "Antiserum raised against a synthetic phosphotyrosine-containing peptide selectively recognizes p185neu/erbB-2 and the epidermal growth factor receptor. Rabbits were immunized with a synthetic phosphopeptide corresponding to a major autophosphorylation site of p185neu/erbB2 to determine the feasibility of producing tyrosine-phosphopeptide-specific antibodies. A series of adsorption and affinity chromatography steps were used to select antibodies with the desired reactivity. Immunoblot experiments showed that the resulting serum is highly specific for tyrosine-phosphorylated forms of p185 and the related epidermal growth factor receptor. The serum recognized these two receptors selectively when compared to five other receptor tyrosine kinases and several phosphorylated substrates. The serum is compatible with tissue-based assays since it detected tyrosine phosphorylation of the epidermal growth factor receptor in immunofluorescence experiments on permeabilized cells. The generality of the procedures used means that similar anti-tyrosine phosphopeptide sera can be produced that recognize other tyrosine kinases and substrates. Such sera will have numerous applications in research and clinical settings."} {"id": "PMID:1280834", "title": "Maximum likelihood estimation and identification directly from single-channel recordings.", "content": "We present a method for analysis of noisy sampled data from a single-channel patch clamp which bypasses restoration of an idealized quantal signal. We show that, even in the absence of a specific model, the conductance levels and mean dwell times within those levels can be estimated. Estimation of the rate constants of a hypothesized kinetic scheme is more difficult. We present examples in which the rate constants can be effectively estimated and examples in which they cannot.", "contents": "Maximum likelihood estimation and identification directly from single-channel recordings. We present a method for analysis of noisy sampled data from a single-channel patch clamp which bypasses restoration of an idealized quantal signal. We show that, even in the absence of a specific model, the conductance levels and mean dwell times within those levels can be estimated. Estimation of the rate constants of a hypothesized kinetic scheme is more difficult. We present examples in which the rate constants can be effectively estimated and examples in which they cannot."} {"id": "PMID:1280835", "title": "Dependency plots suggest the kinetic structure of ion channels.", "content": "Ion channels are integral membrane proteins that regulate ionic flux through cell membranes by opening and closing (gating) their pores. The gating can be monitored by observing step changes in the current flowing through single channels, and analysis of the observed open and closed interval durations has provided a window to develop kinetic models for the gating process. One difficulty in developing such models has been to determine the connections (transition pathways) among the various kinetic states involved in the gating. To help overcome this difficulty we present a transform (dependency plot) of the single-channel data that can give immediate insight into the connections. A dependency plot is derived by calculating a contingency table from a two-dimensional (joint density) dwell-time distribution of adjacent open and closed intervals by assuming that the two classified criteria are the open and closed durations of each pair of adjacent intervals. A three-dimensional surface plot of the fractional difference between the numbers of observed interval pairs and the numbers expected if the durations of adjacent intervals are independent then gives the dependency plot. An excess of interval pairs in the dependency plot suggests that the open and closed states (or compound states) that give rise to the interval pairs in excess are directly connected. A deficit of interval pairs suggests that the open and closed states (or compound states) that give rise to the interval pairs in deficit are either not directly connected or that there are additional open-closed transition pathways arising from the directly connected states.", "contents": "Dependency plots suggest the kinetic structure of ion channels. Ion channels are integral membrane proteins that regulate ionic flux through cell membranes by opening and closing (gating) their pores. The gating can be monitored by observing step changes in the current flowing through single channels, and analysis of the observed open and closed interval durations has provided a window to develop kinetic models for the gating process. One difficulty in developing such models has been to determine the connections (transition pathways) among the various kinetic states involved in the gating. To help overcome this difficulty we present a transform (dependency plot) of the single-channel data that can give immediate insight into the connections. A dependency plot is derived by calculating a contingency table from a two-dimensional (joint density) dwell-time distribution of adjacent open and closed intervals by assuming that the two classified criteria are the open and closed durations of each pair of adjacent intervals. A three-dimensional surface plot of the fractional difference between the numbers of observed interval pairs and the numbers expected if the durations of adjacent intervals are independent then gives the dependency plot. An excess of interval pairs in the dependency plot suggests that the open and closed states (or compound states) that give rise to the interval pairs in excess are directly connected. A deficit of interval pairs suggests that the open and closed states (or compound states) that give rise to the interval pairs in deficit are either not directly connected or that there are additional open-closed transition pathways arising from the directly connected states."} {"id": "PMID:1280836", "title": "Mechano-electrical transducer currents in hair cells of the cultured neonatal mouse cochlea.", "content": "The first step towards the generation of the receptor potential in hair cells is the gating of the transducer channels and subsequent flow of transducer current, induced by deflection of the stereocilia. We describe properties of the transducer current in outer hair cells of neonatal mice. Less extensive observations on inner hair cells suggest that their transducer currents have similar characteristics. The hair bundles were stimulated by force from a fluid jet. The transducer currents in outer hair cells are the largest found so far in any hair cell, with a chord conductance of up to 9.2 nS at -84 mV. The transfer function suggests that the channel has at least two closed states and one open state. The permeabilities for sodium, potassium and caesium are similar, consistent with the channel being a fairly non-selective cation channel. At negative potentials the currents adapt in most cells, although never as completely as in hair cells of lower vertebrates. If the unit conductance of the transducer channel is similar to that of the turtle's auditory hair cells (100 pS), then there are about 90 channels per hair bundle, or one channel between every pair of adjacent stereocilia in neighbouring rows.", "contents": "Mechano-electrical transducer currents in hair cells of the cultured neonatal mouse cochlea. The first step towards the generation of the receptor potential in hair cells is the gating of the transducer channels and subsequent flow of transducer current, induced by deflection of the stereocilia. We describe properties of the transducer current in outer hair cells of neonatal mice. Less extensive observations on inner hair cells suggest that their transducer currents have similar characteristics. The hair bundles were stimulated by force from a fluid jet. The transducer currents in outer hair cells are the largest found so far in any hair cell, with a chord conductance of up to 9.2 nS at -84 mV. The transfer function suggests that the channel has at least two closed states and one open state. The permeabilities for sodium, potassium and caesium are similar, consistent with the channel being a fairly non-selective cation channel. At negative potentials the currents adapt in most cells, although never as completely as in hair cells of lower vertebrates. If the unit conductance of the transducer channel is similar to that of the turtle's auditory hair cells (100 pS), then there are about 90 channels per hair bundle, or one channel between every pair of adjacent stereocilia in neighbouring rows."} {"id": "PMID:1280837", "title": "Inhibition of protein kinases in rat pheochromocytoma (PC12) cells promotes morphological differentiation and down-regulates ion channel expression.", "content": "We have studied morphological differentiation and ion channel expression in PC12 cells under different culture conditions. Differentiation mediated by nerve growth factor (NGF) was compared with that induced by depletion and inhibition of protein kinases (phorbol ester beta-PMA plus staurosporine). Morphological differentiation was similar under both conditions. However, ion channel densities, studied by means of the patch-clamp technique, were enhanced by NGF and reduced by beta-PMA+staurosporine. Similar changes were also observed for omega-conotoxin-sensitive Ca2+ channels by measuring radioligand binding. The decrease in Ca2+ channel density, after treatment of the cells with beta-PMA+staurosporine, resulted in a reduced increase in the intracellular Ca2+ concentration during K+ depolarization. We conclude that morphological differentiation, but not ion channel expression, can occur during depression of protein kinase activities in PC12 cells.", "contents": "Inhibition of protein kinases in rat pheochromocytoma (PC12) cells promotes morphological differentiation and down-regulates ion channel expression. We have studied morphological differentiation and ion channel expression in PC12 cells under different culture conditions. Differentiation mediated by nerve growth factor (NGF) was compared with that induced by depletion and inhibition of protein kinases (phorbol ester beta-PMA plus staurosporine). Morphological differentiation was similar under both conditions. However, ion channel densities, studied by means of the patch-clamp technique, were enhanced by NGF and reduced by beta-PMA+staurosporine. Similar changes were also observed for omega-conotoxin-sensitive Ca2+ channels by measuring radioligand binding. The decrease in Ca2+ channel density, after treatment of the cells with beta-PMA+staurosporine, resulted in a reduced increase in the intracellular Ca2+ concentration during K+ depolarization. We conclude that morphological differentiation, but not ion channel expression, can occur during depression of protein kinase activities in PC12 cells."} {"id": "PMID:1280838", "title": "A new scheme of symbiosis: ligand- and voltage-gated anion channels in plants and animals.", "content": "Anion channels in the plasma membrane of both plant and animal cells participate in a number of important cellular functions such as volume regulation, trans-epithelial transport, stabilization of the membrane potential and excitability. Only very recently attention has turned to the presence of anion channels in higher plant cells. A dominant theme among recent discoveries is the role of Ca2+ in activating or modulating channel current involved in signal transduction. The major anion channel of stomatal guard cell protoplasts is a 32-40 pS channel which is highly selective for anions, in particular NO3-, Cl- and malate. These channels are characterized by a steep voltage dependence. Anion release is elicited upon depolarization and restricted to a narrow voltage span of -100 mV to the reversal potential of anions. During prolonged activation the current slowly inactivates. A rise in cytoplasmic calcium in the presence of nucleotides evokes activation of the anion channels. Following activation they catalyse anion currents 10-20 times higher than in the inactivated state thereby shifting the resting potential of the guard cell from a K(+)-conducting to an anion-conducting state. Patch-clamp studies have also revealed that growth hormones directly affect voltage-dependent activity of the anion channel in a dose-dependent manner. Auxin binding resulted in a shift of the activation potential towards the resting potential. Auxin-dependent gating of the anion channel is side- and hormone-specific. Its action is also channel-specific as K+ channels coexisting in the same membrane patch were insensitive to this ligand.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "A new scheme of symbiosis: ligand- and voltage-gated anion channels in plants and animals. Anion channels in the plasma membrane of both plant and animal cells participate in a number of important cellular functions such as volume regulation, trans-epithelial transport, stabilization of the membrane potential and excitability. Only very recently attention has turned to the presence of anion channels in higher plant cells. A dominant theme among recent discoveries is the role of Ca2+ in activating or modulating channel current involved in signal transduction. The major anion channel of stomatal guard cell protoplasts is a 32-40 pS channel which is highly selective for anions, in particular NO3-, Cl- and malate. These channels are characterized by a steep voltage dependence. Anion release is elicited upon depolarization and restricted to a narrow voltage span of -100 mV to the reversal potential of anions. During prolonged activation the current slowly inactivates. A rise in cytoplasmic calcium in the presence of nucleotides evokes activation of the anion channels. Following activation they catalyse anion currents 10-20 times higher than in the inactivated state thereby shifting the resting potential of the guard cell from a K(+)-conducting to an anion-conducting state. Patch-clamp studies have also revealed that growth hormones directly affect voltage-dependent activity of the anion channel in a dose-dependent manner. Auxin binding resulted in a shift of the activation potential towards the resting potential. Auxin-dependent gating of the anion channel is side- and hormone-specific. Its action is also channel-specific as K+ channels coexisting in the same membrane patch were insensitive to this ligand.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280839", "title": "Calcium- and voltage-dependent ion channels in Saccharomyces cerevisiae.", "content": "Ion channels in both the tonoplast and the plasma membrane of Saccharomyces cerevisiae have been characterized at the single channel level by patch-clamp techniques. The predominant tonoplast channel is cation selective, has an open-channel conductance of 120 pS in 100 mM KCl, and conducts Na+ or K+ equally well, and Ca2+ to a lesser extent. Its open probability (Po) is voltage-dependent, peaking at about -80 mV (cytoplasm negative), and falling to near zero at +80 mV. Elevated cytoplasmic Ca2+, alkaline cytoplasmic pH, and reducing agents activate the channel. The predominant plasma membrane channel is highly selective for K+ over anions and other cations, and shows strong outward rectification of the time-averaged current-voltage curves in cell-attached experiments. In isolated inside-out patches with micromolar cytoplasmic Ca2+, this channel is activated by positive going membrane voltages: mean Po is zero at negative membrane voltages and near unity at 100 mV. At moderate positive membrane voltages (20-40 mV), elevating cytoplasmic Ca2+ activates the channel to open in bursts of several hundred milliseconds duration. At higher positive membrane voltages, however, elevating cytoplasmic Ca2+ blocks the channel in a voltage-dependent fashion for periods of 2-3 ms. The frequency of these blocking events depends on cytoplasmic Ca2+ and membrane voltage according to second-order kinetics. Alternative cations, such as Mg2+ or Na+, block the yeast plasma-membrane K+ channel in a similar but less pronounced manner.", "contents": "Calcium- and voltage-dependent ion channels in Saccharomyces cerevisiae. Ion channels in both the tonoplast and the plasma membrane of Saccharomyces cerevisiae have been characterized at the single channel level by patch-clamp techniques. The predominant tonoplast channel is cation selective, has an open-channel conductance of 120 pS in 100 mM KCl, and conducts Na+ or K+ equally well, and Ca2+ to a lesser extent. Its open probability (Po) is voltage-dependent, peaking at about -80 mV (cytoplasm negative), and falling to near zero at +80 mV. Elevated cytoplasmic Ca2+, alkaline cytoplasmic pH, and reducing agents activate the channel. The predominant plasma membrane channel is highly selective for K+ over anions and other cations, and shows strong outward rectification of the time-averaged current-voltage curves in cell-attached experiments. In isolated inside-out patches with micromolar cytoplasmic Ca2+, this channel is activated by positive going membrane voltages: mean Po is zero at negative membrane voltages and near unity at 100 mV. At moderate positive membrane voltages (20-40 mV), elevating cytoplasmic Ca2+ activates the channel to open in bursts of several hundred milliseconds duration. At higher positive membrane voltages, however, elevating cytoplasmic Ca2+ blocks the channel in a voltage-dependent fashion for periods of 2-3 ms. The frequency of these blocking events depends on cytoplasmic Ca2+ and membrane voltage according to second-order kinetics. Alternative cations, such as Mg2+ or Na+, block the yeast plasma-membrane K+ channel in a similar but less pronounced manner."} {"id": "PMID:1280842", "title": "[Effect of using recombinant human erythropoietin on the effectiveness of hemodialysis in children with terminal renal failure].", "content": "Recombinant human erythropoietin (EPO) was administered to 12 children aged 8-17 years subjected to hemodialysis for a mean period of 16 (S.D. 19.7) months prior to EPO treatment. The hormone was administered thrice weekly at an intravenous dose of 25-75 u/kg until hemoglobin value of 100 g/l was obtained, and subsequently at maintenance doses for mean period of 7 (S.D. 4.0) months. The urea kinetic modeling (UKM) algorithms allowed to compute dialysis index KT/V for each patient in modeling sessions performed once a month. The analysis included the effect of EPO upon: peripheral whole blood count; individual UKM parameters; selected laboratory data (predialysis potassium, phosphorus, creatinine, total blood protein and albumin levels) in three randomized groups according to the value of KT/V: I. KT/V less than or equal to 1.0--underdialyzed, II. KT/V (1.0-1.4)--adequately dialyzed, III. KT/V greater than 1.4--overdialyzed. The results from 188 pre-EPO modeling sessions and 78 sessions in the course of EPO treatment were compared. All the three groups revealed increased Hb, Ht and erythrocyte count in cu mm, statistically significant in Groups II and III. EPO administration resulted in an improvement of dialysis adequacy, increasing the number of adequate modeling sessions from 66 up to 90% and simultaneously reducing the number of sessions in Groups I and III from 9.5 to 2.5% and from 24.5 to 7.5%, respectively. The 2.4% decrease of dialysis index observed after EPO administration was due to increased urea distribution volume.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Effect of using recombinant human erythropoietin on the effectiveness of hemodialysis in children with terminal renal failure]. Recombinant human erythropoietin (EPO) was administered to 12 children aged 8-17 years subjected to hemodialysis for a mean period of 16 (S.D. 19.7) months prior to EPO treatment. The hormone was administered thrice weekly at an intravenous dose of 25-75 u/kg until hemoglobin value of 100 g/l was obtained, and subsequently at maintenance doses for mean period of 7 (S.D. 4.0) months. The urea kinetic modeling (UKM) algorithms allowed to compute dialysis index KT/V for each patient in modeling sessions performed once a month. The analysis included the effect of EPO upon: peripheral whole blood count; individual UKM parameters; selected laboratory data (predialysis potassium, phosphorus, creatinine, total blood protein and albumin levels) in three randomized groups according to the value of KT/V: I. KT/V less than or equal to 1.0--underdialyzed, II. KT/V (1.0-1.4)--adequately dialyzed, III. KT/V greater than 1.4--overdialyzed. The results from 188 pre-EPO modeling sessions and 78 sessions in the course of EPO treatment were compared. All the three groups revealed increased Hb, Ht and erythrocyte count in cu mm, statistically significant in Groups II and III. EPO administration resulted in an improvement of dialysis adequacy, increasing the number of adequate modeling sessions from 66 up to 90% and simultaneously reducing the number of sessions in Groups I and III from 9.5 to 2.5% and from 24.5 to 7.5%, respectively. The 2.4% decrease of dialysis index observed after EPO administration was due to increased urea distribution volume.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280843", "title": "Capsaicin releases calcitonin gene-related peptide from the human iris and ciliary body in vitro.", "content": "Slices of human iris or ciliary body, obtained post-mortem (8-12 h after death, n = 5), were superfused in vitro with capsaicin (10 microM) and the immunoreactivity for substance P (SP-LI) or calcitonin gene-related peptide (CGRP-LI) was measured in the effluent. In the iris and in the ciliary body CGRP-LI was 3.71 +/- 0.74 pmol/g and 3.01 +/- 0.55 pmol/g and SP-LI was 6.68 +/- 0.75 pmol/g and 6.55 +/- 0.84 pmol/g, respectively. A first exposure to capsaicin increased the CGRP-LI outflow from the ciliary body (427 +/- 46 fmol/g/30 min), whereas a second challenge with the drug 30 min later, failed to significantly enhance the CGRP-LI outflow (21.8 +/- 15.6 fmol/g/30 min). Likewise, the capsaicin-evoked increase in CGRP-LI outflow from the iris slices (472 +/- 62 fmol/g/30 min) was no longer observed at the second drug administration (38.4 +/- 12.8 fmol/g/30 min). Capsaicin failed to increase the SP-LI outflow from either the iris or the ciliary body. Reverse phase HPLC analysis of CGRP-LI indicated that authentic CGRP was contained in the tissue and in the superfusate collected during exposure to capsaicin. The present results show that in the human iris and ciliary body, capsaicin releases CGRP possibly contained in terminals of sensory nerves.", "contents": "Capsaicin releases calcitonin gene-related peptide from the human iris and ciliary body in vitro. Slices of human iris or ciliary body, obtained post-mortem (8-12 h after death, n = 5), were superfused in vitro with capsaicin (10 microM) and the immunoreactivity for substance P (SP-LI) or calcitonin gene-related peptide (CGRP-LI) was measured in the effluent. In the iris and in the ciliary body CGRP-LI was 3.71 +/- 0.74 pmol/g and 3.01 +/- 0.55 pmol/g and SP-LI was 6.68 +/- 0.75 pmol/g and 6.55 +/- 0.84 pmol/g, respectively. A first exposure to capsaicin increased the CGRP-LI outflow from the ciliary body (427 +/- 46 fmol/g/30 min), whereas a second challenge with the drug 30 min later, failed to significantly enhance the CGRP-LI outflow (21.8 +/- 15.6 fmol/g/30 min). Likewise, the capsaicin-evoked increase in CGRP-LI outflow from the iris slices (472 +/- 62 fmol/g/30 min) was no longer observed at the second drug administration (38.4 +/- 12.8 fmol/g/30 min). Capsaicin failed to increase the SP-LI outflow from either the iris or the ciliary body. Reverse phase HPLC analysis of CGRP-LI indicated that authentic CGRP was contained in the tissue and in the superfusate collected during exposure to capsaicin. The present results show that in the human iris and ciliary body, capsaicin releases CGRP possibly contained in terminals of sensory nerves."} {"id": "PMID:1280844", "title": "Genetic and environmental factors in the immune pathogenesis of rheumatoid arthritis.", "content": "Our experiments have led us to conclude that the rheumatoid arthritis shared epitope may act as a peptide that is important for positive and negative selection of T lymphocytes, that T lymphocytes are skewed by positive selection to recognize epitopes that are similar but not identical to self, and that peptide sequences that are similar to the RA-shared epitope are abundantly expressed by microorganisms that chronically infect most people. This combination of events could partly explain the association of the shared epitope with the severe forms of RA. The hypothesis cannot be tested directly, because we do not postulate that any unique population of autoreactive T cells is expanded in RA; however, the role of positive selection in molding the human T-cell repertoire to exogenous antigens can be tested by mapping T-cell antigenic determinants on the E. coli dnaJ protein or the gp110 protein of EBV in people with different HLA-DR types. Moreover, positive selection models imply that maternal antigens that cross the placenta can influence the T-cell repertoire. Thus, one might expect to find that the frequency of HLA-DR4 in the mothers of patients with RA who themselves lack the DR4 antigen, would be more frequent than predicted by chance alone. As the principles of positive selection are more precisely delineated in animal systems, it should become possible to ascertain more clearly how the shared epitope on HLA-DR molecules enhances the severity of autoimmune reactions; however, RA only occurs in humans; possibly because of the unique inability of human macrophages to replicate. Thus, only the direct analysis of patients can directly reveal the mechanisms of disease pathogenesis.", "contents": "Genetic and environmental factors in the immune pathogenesis of rheumatoid arthritis. Our experiments have led us to conclude that the rheumatoid arthritis shared epitope may act as a peptide that is important for positive and negative selection of T lymphocytes, that T lymphocytes are skewed by positive selection to recognize epitopes that are similar but not identical to self, and that peptide sequences that are similar to the RA-shared epitope are abundantly expressed by microorganisms that chronically infect most people. This combination of events could partly explain the association of the shared epitope with the severe forms of RA. The hypothesis cannot be tested directly, because we do not postulate that any unique population of autoreactive T cells is expanded in RA; however, the role of positive selection in molding the human T-cell repertoire to exogenous antigens can be tested by mapping T-cell antigenic determinants on the E. coli dnaJ protein or the gp110 protein of EBV in people with different HLA-DR types. Moreover, positive selection models imply that maternal antigens that cross the placenta can influence the T-cell repertoire. Thus, one might expect to find that the frequency of HLA-DR4 in the mothers of patients with RA who themselves lack the DR4 antigen, would be more frequent than predicted by chance alone. As the principles of positive selection are more precisely delineated in animal systems, it should become possible to ascertain more clearly how the shared epitope on HLA-DR molecules enhances the severity of autoimmune reactions; however, RA only occurs in humans; possibly because of the unique inability of human macrophages to replicate. Thus, only the direct analysis of patients can directly reveal the mechanisms of disease pathogenesis."} {"id": "PMID:1280845", "title": "Population genetics of rheumatoid arthritis.", "content": "A major component of genetic susceptibility to rheumatoid arthritis (RA) appears to be explained by inheritance of HLA-DRB1 alleles, which have a conserved sequence of amino acids in the third hyper-variable region of the molecule. This \"shared epitope\" is found on various DR4, DR1, and DR6 variants, as well as on DR10. The evidence for this \"shared epitope\" in RA is examined at the population level, including how it fits in with the available epidemiologic data and RA disease severity.", "contents": "Population genetics of rheumatoid arthritis. A major component of genetic susceptibility to rheumatoid arthritis (RA) appears to be explained by inheritance of HLA-DRB1 alleles, which have a conserved sequence of amino acids in the third hyper-variable region of the molecule. This \"shared epitope\" is found on various DR4, DR1, and DR6 variants, as well as on DR10. The evidence for this \"shared epitope\" in RA is examined at the population level, including how it fits in with the available epidemiologic data and RA disease severity."} {"id": "PMID:1280847", "title": "T-cell receptor-major histocompatibility complex genetic interactions in rheumatoid arthritis.", "content": "Rheumatoid arthritis (RA) is a complex multifactorial illness. It is proposed that multiple genes involved in immune recognition interact to produce a state of genetic susceptibility for RA. The role of HLA and T-cell receptor and other background genes is discussed, with an emphasis on their role in shaping the T-cell repertoire.", "contents": "T-cell receptor-major histocompatibility complex genetic interactions in rheumatoid arthritis. Rheumatoid arthritis (RA) is a complex multifactorial illness. It is proposed that multiple genes involved in immune recognition interact to produce a state of genetic susceptibility for RA. The role of HLA and T-cell receptor and other background genes is discussed, with an emphasis on their role in shaping the T-cell repertoire."} {"id": "PMID:1280848", "title": "Immunotherapy of rheumatic diseases based on understanding genetic predisposition to the development of these diseases.", "content": "During the past two decades, investigators have made great inroads in understanding markers of genetic predisposition to the development of rheumatic diseases. An important question that must be addressed by investigators and clinicians is whether this knowledge will ultimately benefit patients, either through genetic counseling or predictions for beneficial therapeutic intervention. This article discusses various disease mechanisms and modes of immunotherapy such as anti-CD4, major histocompatibility complex blockade, and T-cell receptor-based and determinant-induced responsiveness.", "contents": "Immunotherapy of rheumatic diseases based on understanding genetic predisposition to the development of these diseases. During the past two decades, investigators have made great inroads in understanding markers of genetic predisposition to the development of rheumatic diseases. An important question that must be addressed by investigators and clinicians is whether this knowledge will ultimately benefit patients, either through genetic counseling or predictions for beneficial therapeutic intervention. This article discusses various disease mechanisms and modes of immunotherapy such as anti-CD4, major histocompatibility complex blockade, and T-cell receptor-based and determinant-induced responsiveness."} {"id": "PMID:1280852", "title": "Subretinal membranes in proliferative vitreoretinopathy. An immunohistochemical study.", "content": "Proliferative vitreoretinopathy may be associated with taut subretinal membranes (SRMs) that prevent retinal reattachment. Light microscopic and immunohistochemical procedures were used to identify the cell composition of 15 surgically excised SRMs. Anti glial fibrillary acidic protein (anti-GFAP) and anti S-100 protein stainings were used to examine the distribution of glial cells, and antikeratin staining was used to investigate the distribution of epithelial cells. Our findings confirm the presence of retinal pigment epithelium (RPE) and glial cells in human SRMs. A semiquantitative evaluation of the immunohistochemical studies demonstrated the prevailing role of cells derived from the RPE (48.4%). The glial component of the SRMs appeared to be smaller than in epiretinal membranes, but was not negligible (30.8%). A high incidence (26.6%) of damaged external retina adhered to the SRMs was also observed.", "contents": "Subretinal membranes in proliferative vitreoretinopathy. An immunohistochemical study. Proliferative vitreoretinopathy may be associated with taut subretinal membranes (SRMs) that prevent retinal reattachment. Light microscopic and immunohistochemical procedures were used to identify the cell composition of 15 surgically excised SRMs. Anti glial fibrillary acidic protein (anti-GFAP) and anti S-100 protein stainings were used to examine the distribution of glial cells, and antikeratin staining was used to investigate the distribution of epithelial cells. Our findings confirm the presence of retinal pigment epithelium (RPE) and glial cells in human SRMs. A semiquantitative evaluation of the immunohistochemical studies demonstrated the prevailing role of cells derived from the RPE (48.4%). The glial component of the SRMs appeared to be smaller than in epiretinal membranes, but was not negligible (30.8%). A high incidence (26.6%) of damaged external retina adhered to the SRMs was also observed."} {"id": "PMID:1280853", "title": "[Extrasystole following heart transplantation].", "content": "A 43 year old man developed extensive supraventricular and ventricular extrasystoles (over 500 supraventricular extrasystoles per hour, VES class II) within 3 months after orthotopic heart transplantation because of dilatative cardiomyopathy. At the same time severe graft rejection (class III according to Billingham) was documented. After treatment of the rejection the following three controls by 24 hours Holter EKG showed only slight supraventricular extrasystoles of less than 10 per hour and in three consecutive myocardial biopsies no rejection process requiring additional treatment was found. In individual cases severe ventricular arrhythmia registered by the family doctor may be a first hint for early rejection. Since intervals for inpatient controls have been extended observation of extrasystoles may be helpful for initiation of a next inpatient control. Incidence of extrasystoles after heart transplantation in the cyclosporine-era is discussed.", "contents": "[Extrasystole following heart transplantation]. A 43 year old man developed extensive supraventricular and ventricular extrasystoles (over 500 supraventricular extrasystoles per hour, VES class II) within 3 months after orthotopic heart transplantation because of dilatative cardiomyopathy. At the same time severe graft rejection (class III according to Billingham) was documented. After treatment of the rejection the following three controls by 24 hours Holter EKG showed only slight supraventricular extrasystoles of less than 10 per hour and in three consecutive myocardial biopsies no rejection process requiring additional treatment was found. In individual cases severe ventricular arrhythmia registered by the family doctor may be a first hint for early rejection. Since intervals for inpatient controls have been extended observation of extrasystoles may be helpful for initiation of a next inpatient control. Incidence of extrasystoles after heart transplantation in the cyclosporine-era is discussed."} {"id": "PMID:1280854", "title": "Continuous focal spikes during REM sleep in a case of acquired aphasia (Landau-Kleffner syndrome).", "content": "We report a girl 3 years and 6 months old with onset of aphasia at age 3 years and 3 months. There was no evidence of brain damage and there were no seizures. The neuropsychological evaluation showed that the girl tended to be right-handed, that aphasia was global and that other higher cortical functions seemed to be preserved. Isolated spikes and spikes-and-wave were recorded during wake over the right temporal region with rare independent contralateral abnormalities. During polysomnography (PSG), the physiological patterns of sleep were preserved and right temporal epileptiform discharges were significantly increased in all sleep stages. Maximal activation was obtained at sleep onset and during rapid eye movement (REM) sleep periods, when focal abnormalities became continuous and spread contralaterally. Repeat PSGs showed that the activation profile retained this particular trait, although subclinical discharges tended to increase during slow wave sleep (SWS). This pattern of subclinical temporal status epilepticus during REM sleep differs from the characteristic activation profile found in the syndrome of continuous spikes-and-waves during SWS. However, this profile was transient and all epileptiform changes disappeared during clinical recovery at 18 months of follow-up.", "contents": "Continuous focal spikes during REM sleep in a case of acquired aphasia (Landau-Kleffner syndrome). We report a girl 3 years and 6 months old with onset of aphasia at age 3 years and 3 months. There was no evidence of brain damage and there were no seizures. The neuropsychological evaluation showed that the girl tended to be right-handed, that aphasia was global and that other higher cortical functions seemed to be preserved. Isolated spikes and spikes-and-wave were recorded during wake over the right temporal region with rare independent contralateral abnormalities. During polysomnography (PSG), the physiological patterns of sleep were preserved and right temporal epileptiform discharges were significantly increased in all sleep stages. Maximal activation was obtained at sleep onset and during rapid eye movement (REM) sleep periods, when focal abnormalities became continuous and spread contralaterally. Repeat PSGs showed that the activation profile retained this particular trait, although subclinical discharges tended to increase during slow wave sleep (SWS). This pattern of subclinical temporal status epilepticus during REM sleep differs from the characteristic activation profile found in the syndrome of continuous spikes-and-waves during SWS. However, this profile was transient and all epileptiform changes disappeared during clinical recovery at 18 months of follow-up."} {"id": "PMID:1280855", "title": "Effect of emeriamine on exocrine and endocrine pancreatic function in normal and diabetic rats.", "content": "The effects of emeriamine, a new anti-diabetic drug, on exocrine and endocrine pancreatic function in normal and diabetic rats have been studied both in vivo and in vitro. It was found that emeriamine dose-dependently normalized the symptoms of hyperingestion and hyperposia in streptozotocin (STZ)-induced diabetic rats, with fasting glucose levels significantly decreased and insulin levels not changed. In STZ-induced diabetic rats, there was a significant increase in pancreatic lipase and trypsin contents and a sharp decrease in amylase content. These changes in lipase and trypsin, but not in amylase were normalized by administration of emeriamine. In the normal rat, emeriamine had no effect on either serum glucose or insulin levels, but significantly decreased the pancreatic amylase, lipase as well as trypsin contents by 68%, 58% and 51%, respectively. In vitro, emeriamine (10(-8) - 10(-4) mol l-1) had no effect on enzyme release from pancreatic acini either under basal or carbachol-stimulated conditions. Emeriamine inhibited glucose-induced insulin release from isolated pancreatic islets. In conclusion, emeriamine has an inhibitory effect on synthesis of pancreatic enzymes and on glucose-stimulated insulin release.", "contents": "Effect of emeriamine on exocrine and endocrine pancreatic function in normal and diabetic rats. The effects of emeriamine, a new anti-diabetic drug, on exocrine and endocrine pancreatic function in normal and diabetic rats have been studied both in vivo and in vitro. It was found that emeriamine dose-dependently normalized the symptoms of hyperingestion and hyperposia in streptozotocin (STZ)-induced diabetic rats, with fasting glucose levels significantly decreased and insulin levels not changed. In STZ-induced diabetic rats, there was a significant increase in pancreatic lipase and trypsin contents and a sharp decrease in amylase content. These changes in lipase and trypsin, but not in amylase were normalized by administration of emeriamine. In the normal rat, emeriamine had no effect on either serum glucose or insulin levels, but significantly decreased the pancreatic amylase, lipase as well as trypsin contents by 68%, 58% and 51%, respectively. In vitro, emeriamine (10(-8) - 10(-4) mol l-1) had no effect on enzyme release from pancreatic acini either under basal or carbachol-stimulated conditions. Emeriamine inhibited glucose-induced insulin release from isolated pancreatic islets. In conclusion, emeriamine has an inhibitory effect on synthesis of pancreatic enzymes and on glucose-stimulated insulin release."} {"id": "PMID:1280856", "title": "Functional transcription elongation complexes from synthetic RNA-DNA bubble duplexes.", "content": "A synthetic RNA-DNA bubble duplex construct intended to mimic the nucleic acid framework of a functional transcription elongation complex was designed and assembled. The construct consisted of a double-stranded DNA duplex of variable length (the template and nontemplate strands) containing an internal noncomplementary DNA \"bubble\" sequence. The 3' end of an RNA oligonucleotide that is partially complementary to the template DNA strand was hybridized within the DNA bubble to form an RNA-DNA duplex with a non-complementary 5'-terminal RNA tail. The addition of either Escherichia coli or T7 RNA polymerase to this construct formed a complex that synthesized RNA with good efficiency from the hybridized RNA primer in a template-directed and processive manner, and displayed other features of a normal promoter-initiated transcription elongation complex. Other such constructs can be designed to examine many of the functional and regulatory properties of transcription systems.", "contents": "Functional transcription elongation complexes from synthetic RNA-DNA bubble duplexes. A synthetic RNA-DNA bubble duplex construct intended to mimic the nucleic acid framework of a functional transcription elongation complex was designed and assembled. The construct consisted of a double-stranded DNA duplex of variable length (the template and nontemplate strands) containing an internal noncomplementary DNA \"bubble\" sequence. The 3' end of an RNA oligonucleotide that is partially complementary to the template DNA strand was hybridized within the DNA bubble to form an RNA-DNA duplex with a non-complementary 5'-terminal RNA tail. The addition of either Escherichia coli or T7 RNA polymerase to this construct formed a complex that synthesized RNA with good efficiency from the hybridized RNA primer in a template-directed and processive manner, and displayed other features of a normal promoter-initiated transcription elongation complex. Other such constructs can be designed to examine many of the functional and regulatory properties of transcription systems."} {"id": "PMID:1280857", "title": "Phthalate dioxygenase reductase: a modular structure for electron transfer from pyridine nucleotides to [2Fe-2S].", "content": "Phthalate dioxygenase reductase (PDR) is a prototypical iron-sulfur flavoprotein (36 kilodaltons) that utilizes flavin mononucleotide (FMN) to mediate electron transfer from the two-electron donor, reduced nicotinamide adenine nucleotide (NADH), to the one-electron acceptor, [2Fe-2S]. The crystal structure of oxidized PDR from Pseudomonas cepacia has been analyzed at 2.0 angstrom resolution resolution; reduced PDR and pyridine nucleotide complexes have been analyzed at 2.7 angstrom resolution. NADH, FMN, and the [2Fe-2S] cluster, bound to distinct domains, are brought together near a central cleft in the molecule, with only 4.9 angstroms separating the flavin 8-methyl and a cysteine sulfur ligated to iron. The domains that bind FMN and [2Fe-2S] are packed so that the flavin ring and the plane of the [2Fe-2S] core are approximately perpendicular. The [2Fe-2S] group is bound by four cysteines in a site resembling that in plant ferredoxins, but its redox potential (-174 millivolts at pH 7.0) is much higher than the potentials of plant ferredoxins. Structural and sequence similarities assign PDR to a distinct family of flavoprotein reductases, all related to ferredoxin NADP(+)-reductase.", "contents": "Phthalate dioxygenase reductase: a modular structure for electron transfer from pyridine nucleotides to [2Fe-2S]. Phthalate dioxygenase reductase (PDR) is a prototypical iron-sulfur flavoprotein (36 kilodaltons) that utilizes flavin mononucleotide (FMN) to mediate electron transfer from the two-electron donor, reduced nicotinamide adenine nucleotide (NADH), to the one-electron acceptor, [2Fe-2S]. The crystal structure of oxidized PDR from Pseudomonas cepacia has been analyzed at 2.0 angstrom resolution resolution; reduced PDR and pyridine nucleotide complexes have been analyzed at 2.7 angstrom resolution. NADH, FMN, and the [2Fe-2S] cluster, bound to distinct domains, are brought together near a central cleft in the molecule, with only 4.9 angstroms separating the flavin 8-methyl and a cysteine sulfur ligated to iron. The domains that bind FMN and [2Fe-2S] are packed so that the flavin ring and the plane of the [2Fe-2S] core are approximately perpendicular. The [2Fe-2S] group is bound by four cysteines in a site resembling that in plant ferredoxins, but its redox potential (-174 millivolts at pH 7.0) is much higher than the potentials of plant ferredoxins. Structural and sequence similarities assign PDR to a distinct family of flavoprotein reductases, all related to ferredoxin NADP(+)-reductase."} {"id": "PMID:1280858", "title": "Solution structure of the SH3 domain of Src and identification of its ligand-binding site.", "content": "The Src homology 3 (SH3) region is a protein domain of 55 to 75 amino acids found in many cytoplasmic proteins, including those that participate in signal transduction pathways. The solution structure of the SH3 domain of the tyrosine kinase Src was determined by multidimensional nuclear magnetic resonance methods. The molecule is composed of two short three-stranded anti-parallel beta sheets packed together at approximately right angles. Studies of the SH3 domain bound to proline-rich peptide ligands revealed a hydrophobic binding site on the surface of the protein that is lined with the side chains of conserved aromatic amino acids.", "contents": "Solution structure of the SH3 domain of Src and identification of its ligand-binding site. The Src homology 3 (SH3) region is a protein domain of 55 to 75 amino acids found in many cytoplasmic proteins, including those that participate in signal transduction pathways. The solution structure of the SH3 domain of the tyrosine kinase Src was determined by multidimensional nuclear magnetic resonance methods. The molecule is composed of two short three-stranded anti-parallel beta sheets packed together at approximately right angles. Studies of the SH3 domain bound to proline-rich peptide ligands revealed a hydrophobic binding site on the surface of the protein that is lined with the side chains of conserved aromatic amino acids."} {"id": "PMID:1280860", "title": "Multiglandular disease in seemingly sporadic primary hyperparathyroidism revisited: where are we in the early 1990s? A plea against unilateral parathyroid exploration.", "content": "Most of the available data on multiglandular disease (MGD) originate from long-term series. The spectrum of the disease has changed now because of earlier diagnosis. We decided to assess the current frequency of MGD in seemingly sporadic primary hyperparathyroidism. MGD was defined as the finding that more than one grossly enlarged gland weighed more than 50 mg and the rim of normal parathyroid tissue was diagnostic of adenoma. Nine hundred eight consecutive neck explorations for hyperparathyroidism were performed, 624 before 1989 and 284 between 1989 and 1991, and studied retrospectively. Since 1989, oil Red O staining has been done to assess hyperfunction. When multiple endocrine neoplasia and non-multiple endocrine neoplasia familial cases of hyperparathyroidism are excluded, the frequency of MGD in seemingly sporadic primary hyperparathyroidism, 17.7% before 1989, is still 14% since then, including a 3% frequency of true multiple adenomas. With more restrictive criteria, which exclude the second enlarged gland if it weighed less than 100 mg, if it had no rim, and if oil Red O staining was negative, the frequency of MGD in sporadic hyperparathyroidism has remained 11% since 1989. Unilateral exploration had missed 78% of second enlarged glands, and preoperative imaging studies, when performed, showed more than one gland in only two of 22 cases. Routine bilateral neck exploration is recommended in primary hyperparathyroidism because of a current frequency of MGD of at least 11%.", "contents": "Multiglandular disease in seemingly sporadic primary hyperparathyroidism revisited: where are we in the early 1990s? A plea against unilateral parathyroid exploration. Most of the available data on multiglandular disease (MGD) originate from long-term series. The spectrum of the disease has changed now because of earlier diagnosis. We decided to assess the current frequency of MGD in seemingly sporadic primary hyperparathyroidism. MGD was defined as the finding that more than one grossly enlarged gland weighed more than 50 mg and the rim of normal parathyroid tissue was diagnostic of adenoma. Nine hundred eight consecutive neck explorations for hyperparathyroidism were performed, 624 before 1989 and 284 between 1989 and 1991, and studied retrospectively. Since 1989, oil Red O staining has been done to assess hyperfunction. When multiple endocrine neoplasia and non-multiple endocrine neoplasia familial cases of hyperparathyroidism are excluded, the frequency of MGD in seemingly sporadic primary hyperparathyroidism, 17.7% before 1989, is still 14% since then, including a 3% frequency of true multiple adenomas. With more restrictive criteria, which exclude the second enlarged gland if it weighed less than 100 mg, if it had no rim, and if oil Red O staining was negative, the frequency of MGD in sporadic hyperparathyroidism has remained 11% since 1989. Unilateral exploration had missed 78% of second enlarged glands, and preoperative imaging studies, when performed, showed more than one gland in only two of 22 cases. Routine bilateral neck exploration is recommended in primary hyperparathyroidism because of a current frequency of MGD of at least 11%."} {"id": "PMID:1280861", "title": "[The use of interferon in the combined therapy of juvenile rheumatoid arthritis].", "content": "The efficacy of recombinant gene engineering alpha 2-interferon (reaferon) was studied and compared in 60 patients suffering from verified juvenile rheumatoid arthritis (JRA). Reaferon was shown to possess good tolerance and to produce an adequate therapeutic effect. The combined use of reaferon and methotrexate permits potentiating the therapeutic effect of interferon and avoiding side effects seen with methotrexate used alone. Besides, it makes it possible to reduce the incidence of respiratory infections which are often associated with exacerbation of the underlying disease when treated by conventional methods.", "contents": "[The use of interferon in the combined therapy of juvenile rheumatoid arthritis]. The efficacy of recombinant gene engineering alpha 2-interferon (reaferon) was studied and compared in 60 patients suffering from verified juvenile rheumatoid arthritis (JRA). Reaferon was shown to possess good tolerance and to produce an adequate therapeutic effect. The combined use of reaferon and methotrexate permits potentiating the therapeutic effect of interferon and avoiding side effects seen with methotrexate used alone. Besides, it makes it possible to reduce the incidence of respiratory infections which are often associated with exacerbation of the underlying disease when treated by conventional methods."} {"id": "PMID:1280862", "title": "Influence of heparin and a low molecular weight heparinoid on specific endogenous and exogenous fibrinolytic factors during rest and exercise.", "content": "The effects of heparin (5,000 IU i.v.) and the low molecular weight heparinoid Org 10172 (Orgaran) (3,250 anti-Xa units i.v.) on components of the fibrinolytic system were studied in two double-blind, randomised, placebo-controlled, cross-over trials using healthy subjects. In study A (n = 6) the effects were studied during rest and standardized exercise and in study B (n = 6) during a low dose infusion of recombinant tissue-type plasminogen activator (rt-PA; 80 micrograms over 16 min). At rest, heparin and Org 10172 did not influence the plasma concentrations of endogenous t-PA antigen and activity, urokinase-type PA (u-PA) antigen, plasmin activatable pro-urokinase (scu-PA), active urokinase (tcu-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen. Recombinant t-PA antigen and activity during rt-PA infusion were also not affected. During exercise, neither heparin nor Org 10172 influenced the area under the curve (AUC) of t-PA and u-PA antigen and t-PA activity when compared with placebo. Unexpectedly, after heparin the AUC of t-PA activity was 49% larger (range +19 to +245%) than after Org 10172 (p < 0.05). The last difference was considered spurious, scu-PA, tcu-PA and PAI-1 antigen levels at 2 min after termination of exercise were unaffected by both compounds (p > 0.05). Sulphated polysaccharides do not increase fibrinolytic activity of the plasma by changing the concentrations of the components of the fibrinolytic system.", "contents": "Influence of heparin and a low molecular weight heparinoid on specific endogenous and exogenous fibrinolytic factors during rest and exercise. The effects of heparin (5,000 IU i.v.) and the low molecular weight heparinoid Org 10172 (Orgaran) (3,250 anti-Xa units i.v.) on components of the fibrinolytic system were studied in two double-blind, randomised, placebo-controlled, cross-over trials using healthy subjects. In study A (n = 6) the effects were studied during rest and standardized exercise and in study B (n = 6) during a low dose infusion of recombinant tissue-type plasminogen activator (rt-PA; 80 micrograms over 16 min). At rest, heparin and Org 10172 did not influence the plasma concentrations of endogenous t-PA antigen and activity, urokinase-type PA (u-PA) antigen, plasmin activatable pro-urokinase (scu-PA), active urokinase (tcu-PA) and plasminogen activator inhibitor-1 (PAI-1) antigen. Recombinant t-PA antigen and activity during rt-PA infusion were also not affected. During exercise, neither heparin nor Org 10172 influenced the area under the curve (AUC) of t-PA and u-PA antigen and t-PA activity when compared with placebo. Unexpectedly, after heparin the AUC of t-PA activity was 49% larger (range +19 to +245%) than after Org 10172 (p < 0.05). The last difference was considered spurious, scu-PA, tcu-PA and PAI-1 antigen levels at 2 min after termination of exercise were unaffected by both compounds (p > 0.05). Sulphated polysaccharides do not increase fibrinolytic activity of the plasma by changing the concentrations of the components of the fibrinolytic system."} {"id": "PMID:1280863", "title": "Influence of selected heparins on human neutrophil functions in vitro.", "content": "The effects of four heparin derivatives [unfractionated heparin (UFH) at 5-50 IU/ml, low molecular weight heparin (LMWH) at 2-20 IU/ml, pentasaccharide (Penta) at 5 IU/ml and a synthetic heparinoid (PPS) at 10(-6)-10(-5) M] on various polymorphonuclear (PMN) leukocyte end-functions (aggregation, chemotaxis, phagocytosis and burst) were examined. CR3 expression, actin polymerization and membrane surface charge were also studied to gain more insight on the mechanisms of the action of heparins on PMN. The different heparins were found to have rather different actions. PMN were found to be hyperreactive to PPS. Pentasaccharide hat no effect on PMN functions, while UFH and LMWH had intermediate reactivity, modulating responses in an adenosine-like manner. Interactions of heparins with PMN were attributed to biophysical properties of the molecules rather than to the presence of a specific sequence such as a pentasaccharide. Our results show that certain heparin derivatives, apart their well-known anticoagulant action, modulate polymorphonuclear leukocyte functions that may be involved in vascular injury.", "contents": "Influence of selected heparins on human neutrophil functions in vitro. The effects of four heparin derivatives [unfractionated heparin (UFH) at 5-50 IU/ml, low molecular weight heparin (LMWH) at 2-20 IU/ml, pentasaccharide (Penta) at 5 IU/ml and a synthetic heparinoid (PPS) at 10(-6)-10(-5) M] on various polymorphonuclear (PMN) leukocyte end-functions (aggregation, chemotaxis, phagocytosis and burst) were examined. CR3 expression, actin polymerization and membrane surface charge were also studied to gain more insight on the mechanisms of the action of heparins on PMN. The different heparins were found to have rather different actions. PMN were found to be hyperreactive to PPS. Pentasaccharide hat no effect on PMN functions, while UFH and LMWH had intermediate reactivity, modulating responses in an adenosine-like manner. Interactions of heparins with PMN were attributed to biophysical properties of the molecules rather than to the presence of a specific sequence such as a pentasaccharide. Our results show that certain heparin derivatives, apart their well-known anticoagulant action, modulate polymorphonuclear leukocyte functions that may be involved in vascular injury."} {"id": "PMID:1280864", "title": "Quantitation of platelet glycoprotein IV (CD36) in healthy subjects and in patients with essential thrombocythemia using an immunocapture assay.", "content": "Glycoprotein IV (GPIIb, CD36) is a major platelet membrane glycoprotein which is thought to participate in a number of adhesive reactions and to mediate signal transduction. In order to measure the total content of GPIV in human platelets, we have developed a simple and sensitive solid-phase radioimmunoassay based on the immunocapture of GPIV from Triton X-100-solubilized platelets. FA6-152, a monoclonal antibody to GPIV was coated on microtiter plates and bound antigen was quantified with a radiolabeled polyclonal antibody to GPIV. Using purified GPIV as a standard, the coefficients of variation of the assay were found to be less than 10% at concentrations of GPIV ranging from 0.15 to 0.75 micrograms/ml. The assay was validated by the parallelism obtained between purified GPIV dose-response curves and those obtained with platelet lysates, indicating a similar antigenic activity for GPIV in both samples. The level of GPIV in platelets from healthy donors was 0.23 +/- 0.05 (mean +/- SD, n = 15) micrograms per 100 micrograms of platelet proteins and a mean value of 27,440 +/- 6,200 (SD) molecules per platelet was calculated. The radioimmunoassay could be used to discriminate between the high level of platelet GPIV in patients with essential thrombocythemia (mean +/- SD = 81,850 +/- 27,780 molecules/platelet; n = 8) and the normal GPIV level in patients with secondary thrombocytosis (mean +/- SD = 26,810 +/- 4,030 molecules/platelet; n = 5), thereby demonstrating the clinical usefulness of the assay. The specific increase in platelet GPIV in patients with essential thrombocythemia was confirmed by immunoblot analysis whereas no increase in platelet GPIb or GPIIb-IIIa was observed by this technique.", "contents": "Quantitation of platelet glycoprotein IV (CD36) in healthy subjects and in patients with essential thrombocythemia using an immunocapture assay. Glycoprotein IV (GPIIb, CD36) is a major platelet membrane glycoprotein which is thought to participate in a number of adhesive reactions and to mediate signal transduction. In order to measure the total content of GPIV in human platelets, we have developed a simple and sensitive solid-phase radioimmunoassay based on the immunocapture of GPIV from Triton X-100-solubilized platelets. FA6-152, a monoclonal antibody to GPIV was coated on microtiter plates and bound antigen was quantified with a radiolabeled polyclonal antibody to GPIV. Using purified GPIV as a standard, the coefficients of variation of the assay were found to be less than 10% at concentrations of GPIV ranging from 0.15 to 0.75 micrograms/ml. The assay was validated by the parallelism obtained between purified GPIV dose-response curves and those obtained with platelet lysates, indicating a similar antigenic activity for GPIV in both samples. The level of GPIV in platelets from healthy donors was 0.23 +/- 0.05 (mean +/- SD, n = 15) micrograms per 100 micrograms of platelet proteins and a mean value of 27,440 +/- 6,200 (SD) molecules per platelet was calculated. The radioimmunoassay could be used to discriminate between the high level of platelet GPIV in patients with essential thrombocythemia (mean +/- SD = 81,850 +/- 27,780 molecules/platelet; n = 8) and the normal GPIV level in patients with secondary thrombocytosis (mean +/- SD = 26,810 +/- 4,030 molecules/platelet; n = 5), thereby demonstrating the clinical usefulness of the assay. The specific increase in platelet GPIV in patients with essential thrombocythemia was confirmed by immunoblot analysis whereas no increase in platelet GPIb or GPIIb-IIIa was observed by this technique."} {"id": "PMID:1280865", "title": "Effect of platelet encapsulated Iloprost on platelet aggregation and adhesion to collagen and injured blood vessels in vitro.", "content": "A novel approach to site-directed delivery of drugs in vivo using blood platelets as carrier vehicles is being investigated. In this context some initial studies are reported on the effect of platelet encapsulated anti-platelet drugs on platelet aggregation and adhesion to fibrillar collagen and injured arteries in vitro. The stable prostacyclin analogue Iloprost has been encapsulated within human and pig platelets by high voltage electroporation (Hughes and Crawford 1989 and 1990). After resealing the platelets, the packaged drug has a negligible effect upon platelet adhesion to a surface of fibrillar collagen or to damaged aorta (stripped to the tunica media to simulate deep injury). The rate of platelet recruitment to the collagen shows no dose dependency with respect to intracellular Iloprost concentrations. After high Iloprost loading, as few as 2% drug loaded platelets in a mixture with control (sham encapsulated) platelets, inhibit agonist-induced platelet aggregation > 50%. The prior deposition of a \"lawn\" of Iloprost-loaded platelets onto fibrillar collagen or damaged aorta has a substantial inhibitory effect (50-70%) upon the secondary recruitment of normal platelets compared with recruitment to a \"lawn\" of normal platelets. This inhibition of secondary recruitment occurs even in the presence of a platelet activator. If reduction of platelet recruitment to a vessel wall lesion results in a decrease in the local concentration of platelet granule-derived smooth muscle cell chemotactic and proliferative factors, this site-directed drug delivery may well have application for the prevention of restenosis following balloon angioplasty procedures.", "contents": "Effect of platelet encapsulated Iloprost on platelet aggregation and adhesion to collagen and injured blood vessels in vitro. A novel approach to site-directed delivery of drugs in vivo using blood platelets as carrier vehicles is being investigated. In this context some initial studies are reported on the effect of platelet encapsulated anti-platelet drugs on platelet aggregation and adhesion to fibrillar collagen and injured arteries in vitro. The stable prostacyclin analogue Iloprost has been encapsulated within human and pig platelets by high voltage electroporation (Hughes and Crawford 1989 and 1990). After resealing the platelets, the packaged drug has a negligible effect upon platelet adhesion to a surface of fibrillar collagen or to damaged aorta (stripped to the tunica media to simulate deep injury). The rate of platelet recruitment to the collagen shows no dose dependency with respect to intracellular Iloprost concentrations. After high Iloprost loading, as few as 2% drug loaded platelets in a mixture with control (sham encapsulated) platelets, inhibit agonist-induced platelet aggregation > 50%. The prior deposition of a \"lawn\" of Iloprost-loaded platelets onto fibrillar collagen or damaged aorta has a substantial inhibitory effect (50-70%) upon the secondary recruitment of normal platelets compared with recruitment to a \"lawn\" of normal platelets. This inhibition of secondary recruitment occurs even in the presence of a platelet activator. If reduction of platelet recruitment to a vessel wall lesion results in a decrease in the local concentration of platelet granule-derived smooth muscle cell chemotactic and proliferative factors, this site-directed drug delivery may well have application for the prevention of restenosis following balloon angioplasty procedures."} {"id": "PMID:1280866", "title": "A case of pulmonary hyalinizing granuloma.", "content": "A case of pulmonary hyalinizing granuloma was presented. The patient was a 37-year-old male who was found to have abnormal chest roentgenograms showing multiple pulmonary nodules taken at the annual chest mass survey in October 1989. The largest nodule measured 35 mm in diameter. He was asymptomatic. No definite diagnosis was established either by brushing cytology, biopsy through bronchoscopy or percutaneous needle biopsy. No abnormalities were found in the GI tract, the urogenital system or the bone. Brain CT indicated an iso-density area surrounded by low density in the left fronto-parietal region. Two nodules of the lingula removed by open lung biopsy revealed a homogeneous cut surface. Histological diagnosis was pulmonary hyalinizing granuloma, consisting of hyalinized collagen fibers and bundles infiltrated with chronic inflammatory cells. No therapeutic effect was recognized with prednisolone. Craniotomy was performed and the brain lesion was removed. Anaplastic astrocytoma was the diagnosis. The brain lesion had no etiological correlation with pulmonary hyalinizing granuloma. Pulmonary hyalinizing granuloma itself is a rare benign disease with no specific therapy and is important in the differential diagnosis of lung diseases showing multiple pulmonary nodules.", "contents": "A case of pulmonary hyalinizing granuloma. A case of pulmonary hyalinizing granuloma was presented. The patient was a 37-year-old male who was found to have abnormal chest roentgenograms showing multiple pulmonary nodules taken at the annual chest mass survey in October 1989. The largest nodule measured 35 mm in diameter. He was asymptomatic. No definite diagnosis was established either by brushing cytology, biopsy through bronchoscopy or percutaneous needle biopsy. No abnormalities were found in the GI tract, the urogenital system or the bone. Brain CT indicated an iso-density area surrounded by low density in the left fronto-parietal region. Two nodules of the lingula removed by open lung biopsy revealed a homogeneous cut surface. Histological diagnosis was pulmonary hyalinizing granuloma, consisting of hyalinized collagen fibers and bundles infiltrated with chronic inflammatory cells. No therapeutic effect was recognized with prednisolone. Craniotomy was performed and the brain lesion was removed. Anaplastic astrocytoma was the diagnosis. The brain lesion had no etiological correlation with pulmonary hyalinizing granuloma. Pulmonary hyalinizing granuloma itself is a rare benign disease with no specific therapy and is important in the differential diagnosis of lung diseases showing multiple pulmonary nodules."} {"id": "PMID:1280867", "title": "The acute phase response of rats to soman intoxication.", "content": "The capacity of an organophosphate to elicit the acute phase response (APR) was assessed by studying the effects of acute soman intoxication on two major processes which characterize inflammation, cytokine production in macrophages and the expression of acute phase protein (APP) genes in the liver. It was established that the concentration of lymphostimulatory substances secreted by the macrophages of soman-intoxicated rats was increased to a level characteristic of the primary inflammatory reaction. Macrophage activation was followed by increased transcription rates of APP genes and the corresponding mRNA and protein synthesis in the liver. The pattern of the DNA-protein complexes obtained with nuclear extracts and the cis-element of the rat haptoglobin gene in the gel-retardation assay suggested that the molecular events which underlie the expression of APP genes of intoxicated rats are similar to those that occur during the APR. From these findings we concluded that soman intoxication was a metabolic injury which elicited the typical APR.", "contents": "The acute phase response of rats to soman intoxication. The capacity of an organophosphate to elicit the acute phase response (APR) was assessed by studying the effects of acute soman intoxication on two major processes which characterize inflammation, cytokine production in macrophages and the expression of acute phase protein (APP) genes in the liver. It was established that the concentration of lymphostimulatory substances secreted by the macrophages of soman-intoxicated rats was increased to a level characteristic of the primary inflammatory reaction. Macrophage activation was followed by increased transcription rates of APP genes and the corresponding mRNA and protein synthesis in the liver. The pattern of the DNA-protein complexes obtained with nuclear extracts and the cis-element of the rat haptoglobin gene in the gel-retardation assay suggested that the molecular events which underlie the expression of APP genes of intoxicated rats are similar to those that occur during the APR. From these findings we concluded that soman intoxication was a metabolic injury which elicited the typical APR."} {"id": "PMID:1280869", "title": "Nitric oxide as a signal in blood vessels.", "content": "In the five years since the discovery that nitric oxide is produced as a signal in blood vessels, a great deal has been discovered about the processes involved. This article reviews current knowledge about the vascular cell synthesis, effects and subsequent destruction of this messenger molecule.", "contents": "Nitric oxide as a signal in blood vessels. In the five years since the discovery that nitric oxide is produced as a signal in blood vessels, a great deal has been discovered about the processes involved. This article reviews current knowledge about the vascular cell synthesis, effects and subsequent destruction of this messenger molecule."} {"id": "PMID:1280870", "title": "Foetal haemoglobin in Nigerian children with sickle cell anaemia. Effect on haematological parameters and clinical severity.", "content": "The relationship of foetal haemoglobin (HbF) to several clinical and haematological parameters in 86 children aged 5 to 16 years who had sickle cell anaemia (SCA) has been examined. The mean HbF level was 6.8 +/- 3.6%. Higher HbF values were significantly associated with fewer blood transfusions, fewer hospital admissions and higher rate of hepatomegaly. A trend for children with higher HbF levels to have better physical development and a more normal haemogram was also noted though this was not statistically significant.", "contents": "Foetal haemoglobin in Nigerian children with sickle cell anaemia. Effect on haematological parameters and clinical severity. The relationship of foetal haemoglobin (HbF) to several clinical and haematological parameters in 86 children aged 5 to 16 years who had sickle cell anaemia (SCA) has been examined. The mean HbF level was 6.8 +/- 3.6%. Higher HbF values were significantly associated with fewer blood transfusions, fewer hospital admissions and higher rate of hepatomegaly. A trend for children with higher HbF levels to have better physical development and a more normal haemogram was also noted though this was not statistically significant."} {"id": "PMID:1280868", "title": "[The use of gel chromatography for the purification of beta-adrenoblockaders isolated from cadaveric material].", "content": "Efficacy of gel chromatography for purification of extracts from cadaveric material containing beta-adrenoblockers was shown in model tests. Distribution curves and chromatographic features of beta-adrenoblockers obtained on hydrophilic and lipophilic-hydrophilic Sephadex were studied.", "contents": "[The use of gel chromatography for the purification of beta-adrenoblockaders isolated from cadaveric material]. Efficacy of gel chromatography for purification of extracts from cadaveric material containing beta-adrenoblockers was shown in model tests. Distribution curves and chromatographic features of beta-adrenoblockers obtained on hydrophilic and lipophilic-hydrophilic Sephadex were studied."} {"id": "PMID:1280871", "title": "[The regulation of protein kinase C activity in normal, immortalized and transformed rat fibroblasts].", "content": "In view of recent studies showing that cell proliferation of E1Aad5+c-Ha-ras-transformed fibroblasts cannot be regulated by growth factors and phorbol eaters in contrast to normal and E1Aad5-immortalized cell lines, the present work was undertaken to examine the role of protein kinase C (PKC) in the mitogenic signal transduction machinery in rat embryonal fibroblasts. It is shown that PKC is activated by acidic growth factor and phorbol esters in all the three cell lines. These findings suggest the existence of an additional, not associated with PKC-, growth-signaling pathway in E1Aad5-Ha-ras-transformed rat embryonal fibroblasts.", "contents": "[The regulation of protein kinase C activity in normal, immortalized and transformed rat fibroblasts]. In view of recent studies showing that cell proliferation of E1Aad5+c-Ha-ras-transformed fibroblasts cannot be regulated by growth factors and phorbol eaters in contrast to normal and E1Aad5-immortalized cell lines, the present work was undertaken to examine the role of protein kinase C (PKC) in the mitogenic signal transduction machinery in rat embryonal fibroblasts. It is shown that PKC is activated by acidic growth factor and phorbol esters in all the three cell lines. These findings suggest the existence of an additional, not associated with PKC-, growth-signaling pathway in E1Aad5-Ha-ras-transformed rat embryonal fibroblasts."} {"id": "PMID:1280872", "title": "[The localization of DNA in the nucleoli of mammalian cells].", "content": "The localization of DNA within nucleoli of mammalian cells was studied in human diploid fibroblasts (strain MRC-5), stained with chromomycin A3--the fluorochrome specific for G-C DNA base pairs. To change the rate of rDNA transcription, actinomycin D (0.08 mkg/ml) was added to log phase cells for 30-90 min. The stained cells were analysed with a highly sensitive video camera and deblurring algorithm (Jordan, Rawlins, 1990). The pattern of staining was compared with the ultrastructural peculiarities of the cells fixed in the same conditions. As the result, it is inferred that the intranucleolar DNA (rDNA) is consistent with the fibrillar centres as well as with the dense fibrillar component. The localization of rDNA may alter due to the transcriptional activity of ribosomal genes. The data obtained support the idea on the transcription of ribosomal genes inside the dense fibrillar component of the nucleolus.", "contents": "[The localization of DNA in the nucleoli of mammalian cells]. The localization of DNA within nucleoli of mammalian cells was studied in human diploid fibroblasts (strain MRC-5), stained with chromomycin A3--the fluorochrome specific for G-C DNA base pairs. To change the rate of rDNA transcription, actinomycin D (0.08 mkg/ml) was added to log phase cells for 30-90 min. The stained cells were analysed with a highly sensitive video camera and deblurring algorithm (Jordan, Rawlins, 1990). The pattern of staining was compared with the ultrastructural peculiarities of the cells fixed in the same conditions. As the result, it is inferred that the intranucleolar DNA (rDNA) is consistent with the fibrillar centres as well as with the dense fibrillar component. The localization of rDNA may alter due to the transcriptional activity of ribosomal genes. The data obtained support the idea on the transcription of ribosomal genes inside the dense fibrillar component of the nucleolus."} {"id": "PMID:1280873", "title": "Obstructive nephropathy in the pig. Possible roles for insulin-like growth factor I.", "content": "Kidney growth was investigated in 30-kg pigs after 72 h of unilateral ureteral obstruction. The data were compared to control kidneys from normal non-operated pigs at same weight. Kidney wet weight was determined. Cortex and medulla were separated, and from both regions RNA, DNA, protein and kidney tissue insulin-like growth factor I was determined. Unilateral obstruction caused a doubling of the wet hydronephrotic kidney weight and an ipsilateral 76% increase in total kidney protein content. RNA increased by 45% in the cortex and 76% in the medulla. Kidney protein in the contralateral cortex increased by 23% and RNA by 42%. In the hydronephrotic kidney DNA was reduced by 13% in the cortex and by 21% in the medulla. Contralaterally, DNA was the same as in the controls. Mean kidney insulin-like growth factor I increased sevenfold in the ipsilateral medulla but in the cortex it was the same as in the controls. Serum insulin-like growth factor I concentration was 1.7 +/- 1.1 micrograms/l in the hydronephrotic animals and 1.2 +/- 0.8 micrograms/l in controls. At this stage of obstruction, our data demonstrate (1) hydronephrotic growth that is most probably hyperplastic in the medulla, associated with an increase in medullary insulin-like growth factor I, (2) hyperplastic growth in the cortex, and (3) contralateral kidney growth that is mainly hypertrophic after 72 h of contralateral ureteral obstruction.", "contents": "Obstructive nephropathy in the pig. Possible roles for insulin-like growth factor I. Kidney growth was investigated in 30-kg pigs after 72 h of unilateral ureteral obstruction. The data were compared to control kidneys from normal non-operated pigs at same weight. Kidney wet weight was determined. Cortex and medulla were separated, and from both regions RNA, DNA, protein and kidney tissue insulin-like growth factor I was determined. Unilateral obstruction caused a doubling of the wet hydronephrotic kidney weight and an ipsilateral 76% increase in total kidney protein content. RNA increased by 45% in the cortex and 76% in the medulla. Kidney protein in the contralateral cortex increased by 23% and RNA by 42%. In the hydronephrotic kidney DNA was reduced by 13% in the cortex and by 21% in the medulla. Contralaterally, DNA was the same as in the controls. Mean kidney insulin-like growth factor I increased sevenfold in the ipsilateral medulla but in the cortex it was the same as in the controls. Serum insulin-like growth factor I concentration was 1.7 +/- 1.1 micrograms/l in the hydronephrotic animals and 1.2 +/- 0.8 micrograms/l in controls. At this stage of obstruction, our data demonstrate (1) hydronephrotic growth that is most probably hyperplastic in the medulla, associated with an increase in medullary insulin-like growth factor I, (2) hyperplastic growth in the cortex, and (3) contralateral kidney growth that is mainly hypertrophic after 72 h of contralateral ureteral obstruction."} {"id": "PMID:1280874", "title": "Effects of cytokines on growth in vitro of primary human renal cell carcinoma.", "content": "In clinical trials different haematopoietic active cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) have been proven to alleviate myelosuppressive side effects of intensive chemotherapy in different non-urological malignancies. On the other hand, these cytokines can directly stimulate the proliferation of cells originating from some non-urological tumours. To clarify the impact of these cytokines on the proliferative behaviour of human renal cell carcinoma (RCC), 29 previously untreated RCC tumours were prepared for culturing in vitro using the cell cluster technique. The success rate for growth in vitro was 82.8% (24/29). The malignant renal cells were treated with different cytokines (GM-CSF, G-CSF and interleukin-3) in different dosages. Cell number and proliferation rates detected by immunostaining were used for treatment evaluation. A dosage-dependent stimulation of cell growth could not be observed compared to untreated cells. From the data presented in this study, proliferative stimulation of RCC by administering colony-stimulating factors in clinical trials cannot be assumed.", "contents": "Effects of cytokines on growth in vitro of primary human renal cell carcinoma. In clinical trials different haematopoietic active cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) have been proven to alleviate myelosuppressive side effects of intensive chemotherapy in different non-urological malignancies. On the other hand, these cytokines can directly stimulate the proliferation of cells originating from some non-urological tumours. To clarify the impact of these cytokines on the proliferative behaviour of human renal cell carcinoma (RCC), 29 previously untreated RCC tumours were prepared for culturing in vitro using the cell cluster technique. The success rate for growth in vitro was 82.8% (24/29). The malignant renal cells were treated with different cytokines (GM-CSF, G-CSF and interleukin-3) in different dosages. Cell number and proliferation rates detected by immunostaining were used for treatment evaluation. A dosage-dependent stimulation of cell growth could not be observed compared to untreated cells. From the data presented in this study, proliferative stimulation of RCC by administering colony-stimulating factors in clinical trials cannot be assumed."} {"id": "PMID:1280875", "title": "Development of a control strategy for Leptospira hardjo infection in a closed beef herd.", "content": "Serological evidence of infection with a leptospire belonging to the Sejroe serogroup was identified in a closed population of Luing cattle in the west of Scotland, and the geographical isolation of the population presented an opportunity to control and possibly eradicate the infection in a large beef herd farmed under extensive conditions. Serological and bacteriological studies revealed that infection was present at a high level throughout the herd, and that the infecting serovar was hardjo. Unlike endemic hardjo infection in dairy herds, new infections were still occurring in older age-groups. Investigations of other domestic and free-living species sharing the habitat demonstrated that the maintenance of an endemic focus of hardjo was restricted to the cattle. Changes in management to prevent the transmission of infection to successive cohorts of young animals were impractical and risky, and antibiotic treatment followed by removal to clean pasture failed to prevent new cases. Thus vaccination offered the only means of control and possible eradication, and the epidemiological characteristics of the infection dictated that the programme be applied to the whole herd.", "contents": "Development of a control strategy for Leptospira hardjo infection in a closed beef herd. Serological evidence of infection with a leptospire belonging to the Sejroe serogroup was identified in a closed population of Luing cattle in the west of Scotland, and the geographical isolation of the population presented an opportunity to control and possibly eradicate the infection in a large beef herd farmed under extensive conditions. Serological and bacteriological studies revealed that infection was present at a high level throughout the herd, and that the infecting serovar was hardjo. Unlike endemic hardjo infection in dairy herds, new infections were still occurring in older age-groups. Investigations of other domestic and free-living species sharing the habitat demonstrated that the maintenance of an endemic focus of hardjo was restricted to the cattle. Changes in management to prevent the transmission of infection to successive cohorts of young animals were impractical and risky, and antibiotic treatment followed by removal to clean pasture failed to prevent new cases. Thus vaccination offered the only means of control and possible eradication, and the epidemiological characteristics of the infection dictated that the programme be applied to the whole herd."} {"id": "PMID:1280876", "title": "Immune responses of specific pathogen free foals to EHV-1 infection.", "content": "Four foals were raised under specific pathogen free (SPF) conditions. At 3 to 4 months of age, SPF foals and 1 other non-SPF foal were intranasally inoculated with equine herpes virus type 1 (EHV-1). Clinical signs included depression, fever, inappetence and intermittent coughing. Clinical recovery was complete by seven days but high titres of virus were detected in nasal mucus for at least 10 days after inoculation. Clinical illness was less severe in the non-SPF foal. Interferon was detected in the nasal mucus of all foals from 2 days post infection (dpi), persisting until 8 or 10 dpi. ELISA antibody was detected in serum from 6 dpi. Titres continued to rise throughout the period of observation, and were slightly stimulated by re-inoculation. EHV antibody, identified as belonging to the IgM class by the double sandwich ELISA, was detected from 6 dpi. Peak IgM titres were observed between day 10 and 18, declining to base levels by day 42. Virus neutralizing antibody was detectable in serum from day 14 and rises in titre were parallel to that of total ELISA antibody. Cellular immunity in EHV-1 infected SPF horses was examined by the antibody dependent cytotoxicity (ADCC) test and the specific lymphocyte transformation test. The ability of foal neutrophils to effect ADCC decreased significantly between 3 to 10 days after inoculation. Peripheral blood mononuclear cells (PBMC) displayed reactivity towards EHV-1 antigens from about day 14, with maximum stimulation indices being obtained between 28 and 42 dpi.", "contents": "Immune responses of specific pathogen free foals to EHV-1 infection. Four foals were raised under specific pathogen free (SPF) conditions. At 3 to 4 months of age, SPF foals and 1 other non-SPF foal were intranasally inoculated with equine herpes virus type 1 (EHV-1). Clinical signs included depression, fever, inappetence and intermittent coughing. Clinical recovery was complete by seven days but high titres of virus were detected in nasal mucus for at least 10 days after inoculation. Clinical illness was less severe in the non-SPF foal. Interferon was detected in the nasal mucus of all foals from 2 days post infection (dpi), persisting until 8 or 10 dpi. ELISA antibody was detected in serum from 6 dpi. Titres continued to rise throughout the period of observation, and were slightly stimulated by re-inoculation. EHV antibody, identified as belonging to the IgM class by the double sandwich ELISA, was detected from 6 dpi. Peak IgM titres were observed between day 10 and 18, declining to base levels by day 42. Virus neutralizing antibody was detectable in serum from day 14 and rises in titre were parallel to that of total ELISA antibody. Cellular immunity in EHV-1 infected SPF horses was examined by the antibody dependent cytotoxicity (ADCC) test and the specific lymphocyte transformation test. The ability of foal neutrophils to effect ADCC decreased significantly between 3 to 10 days after inoculation. Peripheral blood mononuclear cells (PBMC) displayed reactivity towards EHV-1 antigens from about day 14, with maximum stimulation indices being obtained between 28 and 42 dpi."} {"id": "PMID:1280877", "title": "A characterization of monoclonal antibodies prepared against Pasteurella haemolytica serotype 1 surface antigens.", "content": "The production and characterization of monoclonal antibodies against Pasteurella haemolytica serotype 1 is described. Ten monoclonal antibodies were produced and divided, on the basis of their properties, into six different groups. One produced bacteria agglutination only of P. haemolytica serotype 1. Three antibodies bound with P. haemolytica serotypes 1, 5-8 and 12 and the antigen was identified in immunoblots as lipopolysaccharide. Two antibodies bound P. haemolytica serotypes 1, 2, 5-8 and 12 and P. multocida serotypes 1-7, 9, 12, 15 and 16, recognizing an epitope present on a 29 kDa outer membrane protein. One antibody bound all P. haemolytica and P. multocida serotypes. The antigen was a hexosamine less than 30 kDa which contained a formalin sensitive epitope. One antibody bound only to P. haemolytica serotype 1 and the antigen was identified as a 66 kDa outer membrane protein. Two antibodies bound P. haemolytica serotypes 1, 2, 5-9 and 12 and the antigen, while not identified, was localized on the outer membrane. This study identified antigens which contribute to the cross-reactions among P. haemolytica and P. multocida serotypes and the antibodies may be useful in investigating the pathogenesis of pneumonic pasteurellosis.", "contents": "A characterization of monoclonal antibodies prepared against Pasteurella haemolytica serotype 1 surface antigens. The production and characterization of monoclonal antibodies against Pasteurella haemolytica serotype 1 is described. Ten monoclonal antibodies were produced and divided, on the basis of their properties, into six different groups. One produced bacteria agglutination only of P. haemolytica serotype 1. Three antibodies bound with P. haemolytica serotypes 1, 5-8 and 12 and the antigen was identified in immunoblots as lipopolysaccharide. Two antibodies bound P. haemolytica serotypes 1, 2, 5-8 and 12 and P. multocida serotypes 1-7, 9, 12, 15 and 16, recognizing an epitope present on a 29 kDa outer membrane protein. One antibody bound all P. haemolytica and P. multocida serotypes. The antigen was a hexosamine less than 30 kDa which contained a formalin sensitive epitope. One antibody bound only to P. haemolytica serotype 1 and the antigen was identified as a 66 kDa outer membrane protein. Two antibodies bound P. haemolytica serotypes 1, 2, 5-9 and 12 and the antigen, while not identified, was localized on the outer membrane. This study identified antigens which contribute to the cross-reactions among P. haemolytica and P. multocida serotypes and the antibodies may be useful in investigating the pathogenesis of pneumonic pasteurellosis."} {"id": "PMID:1280878", "title": "Common and stage-specific antigens of Theileria annulata.", "content": "Western blot analysis of Theileria annulata antigens was carried out using sera collected from cattle which had been immunised and challenged with either T. annulata sporozoites or schizont-infected cells. Three antigens between 71 and 73 kDa proved to be common to the three stages of parasite studied: sporozoites, schizonts and piroplasms. An antigen was found at 32 kDa which was specific to T. annulata piroplasms. Results were reproducible using sera from Morocco and the UK. At least one of the proteins at 71-73 kDa, but not that at 32 kDa were also recognised by sera from animals infected with Babesia species.", "contents": "Common and stage-specific antigens of Theileria annulata. Western blot analysis of Theileria annulata antigens was carried out using sera collected from cattle which had been immunised and challenged with either T. annulata sporozoites or schizont-infected cells. Three antigens between 71 and 73 kDa proved to be common to the three stages of parasite studied: sporozoites, schizonts and piroplasms. An antigen was found at 32 kDa which was specific to T. annulata piroplasms. Results were reproducible using sera from Morocco and the UK. At least one of the proteins at 71-73 kDa, but not that at 32 kDa were also recognised by sera from animals infected with Babesia species."} {"id": "PMID:1280879", "title": "Immunostimulants added to injected Aeromonas salmonicida bacterin enhance the defense mechanisms and protection in rainbow trout (Oncorhynchus mykiss).", "content": "Immunostimulants were given to rainbow trout for assaying effects on modulating non-specific defense mechanisms, specific immune response, and protection levels against pathogen challenge with Aeromonas salmonicida. Three drugs, levamisole (an approved veterinary drug in the USA), a quaternary ammonium compound (QAC), and a short-chain polypeptide (ISK) were found to affect the non-specific defense mechanism activities, which were measured by changes in circulatory neutrophil and phagocytic activity levels, and the specific immune response factors, which were measured by numbers of plaque-forming cells, and circulatory antibody levels. When given alone, the immunostimulants elevated the non-specific factors. When injected in combination with an A. salmonicida O-antigen bacterin, the non-specific factors were further elevated, and the specific response was raised over samples taken from fish given the bacterin without the immunostimulants. Challenge tests with the virulent pathogen, A. salmonicida, showed a 5-6 day delay in the onset of mortalities in the fish given the immunostimulants alone, and a 12-14 day delay when immunostimulants given were combined with the bacterin. In the groups given the QAC or ISK with the bacterin, there was a 20% and 40% survival rate, respectively.", "contents": "Immunostimulants added to injected Aeromonas salmonicida bacterin enhance the defense mechanisms and protection in rainbow trout (Oncorhynchus mykiss). Immunostimulants were given to rainbow trout for assaying effects on modulating non-specific defense mechanisms, specific immune response, and protection levels against pathogen challenge with Aeromonas salmonicida. Three drugs, levamisole (an approved veterinary drug in the USA), a quaternary ammonium compound (QAC), and a short-chain polypeptide (ISK) were found to affect the non-specific defense mechanism activities, which were measured by changes in circulatory neutrophil and phagocytic activity levels, and the specific immune response factors, which were measured by numbers of plaque-forming cells, and circulatory antibody levels. When given alone, the immunostimulants elevated the non-specific factors. When injected in combination with an A. salmonicida O-antigen bacterin, the non-specific factors were further elevated, and the specific response was raised over samples taken from fish given the bacterin without the immunostimulants. Challenge tests with the virulent pathogen, A. salmonicida, showed a 5-6 day delay in the onset of mortalities in the fish given the immunostimulants alone, and a 12-14 day delay when immunostimulants given were combined with the bacterin. In the groups given the QAC or ISK with the bacterin, there was a 20% and 40% survival rate, respectively."} {"id": "PMID:1280880", "title": "Multicystic mesothelial proliferation. Immunohistochemical, ultrastructural and DNA analysis of five cases.", "content": "We investigated the clinicopathological findings in five cases of multicystic mesothelial proliferation (MMP). All masses consisted of multiloculated cysts attached to pelvic organs and sometimes growing into the upper abdominal cavity. The cystic spaces were lined by flattened or cuboidal cells. The stroma showed fibrosis, oedema and chronic inflammation. Immunohistochemistry revealed strong positive staining for cytokeratin and epithelial membrane antigen, and focal positivity for vimentin and carcinoembryonic antigen. The endothelial markers were negative. Electron microscopy showed abundant surface microvilli and well-developed basal lamina. DNA analysis identified euploid cell populations in all cases. All but one case had a previous history of abdominal surgery. Despite the worrying appearance the clinical outcome was favourable in all cases; there was one recurrence. Clinical and pathological data support the hypothesis that MMP represent a reactive mesothelial proliferation and not a neoplastic process.", "contents": "Multicystic mesothelial proliferation. Immunohistochemical, ultrastructural and DNA analysis of five cases. We investigated the clinicopathological findings in five cases of multicystic mesothelial proliferation (MMP). All masses consisted of multiloculated cysts attached to pelvic organs and sometimes growing into the upper abdominal cavity. The cystic spaces were lined by flattened or cuboidal cells. The stroma showed fibrosis, oedema and chronic inflammation. Immunohistochemistry revealed strong positive staining for cytokeratin and epithelial membrane antigen, and focal positivity for vimentin and carcinoembryonic antigen. The endothelial markers were negative. Electron microscopy showed abundant surface microvilli and well-developed basal lamina. DNA analysis identified euploid cell populations in all cases. All but one case had a previous history of abdominal surgery. Despite the worrying appearance the clinical outcome was favourable in all cases; there was one recurrence. Clinical and pathological data support the hypothesis that MMP represent a reactive mesothelial proliferation and not a neoplastic process."} {"id": "PMID:1280881", "title": "Epithelioid sarcoma: an electron-microscopic, immunohistochemical and DNA flow cytometric analysis.", "content": "Eight epithelioid sarcomas (ES) were studied by electron microscopy, immunohistochemistry, and DNA flow cytometry. Ultrastructurally, the tumour cells showed desmosome-like intercellular junctions and numerous microvilli, in addition to whorled arrangements of intermediate filaments. Tumour cells were positive for epithelial membrane antigen, cytokeratin, and vimentin, and negative for carcinoembryonic antigen and desmin. All seven cases examined by flow cytometry showed diploid or hyperploid (near diploid) DNA content. This seems to correspond to the relatively long clinical course and low-grade malignant nature of ES. Although the histogenesis of ES is still uncertain, the results of this study suggest that it is a tumour of primitive mesenchymal cells with the capacity to show epithelial differentiation.", "contents": "Epithelioid sarcoma: an electron-microscopic, immunohistochemical and DNA flow cytometric analysis. Eight epithelioid sarcomas (ES) were studied by electron microscopy, immunohistochemistry, and DNA flow cytometry. Ultrastructurally, the tumour cells showed desmosome-like intercellular junctions and numerous microvilli, in addition to whorled arrangements of intermediate filaments. Tumour cells were positive for epithelial membrane antigen, cytokeratin, and vimentin, and negative for carcinoembryonic antigen and desmin. All seven cases examined by flow cytometry showed diploid or hyperploid (near diploid) DNA content. This seems to correspond to the relatively long clinical course and low-grade malignant nature of ES. Although the histogenesis of ES is still uncertain, the results of this study suggest that it is a tumour of primitive mesenchymal cells with the capacity to show epithelial differentiation."} {"id": "PMID:1280882", "title": "Immunohistochemical and ultrastructural studies of intraluminal crystalloids in human prostatic carcinomas.", "content": "Intraluminal crystalloids (ICr) observed in 19 cases of incidental or invasive human prostatic carcinoma (PCa) and in a case of benign prostatic hyperplasia were examined extensively by immunohistochemistry and electron microscopy. They were brilliantly eosinophilic with haematoxylin and eosin, manifesting needle-like, triangular, rectangular, hexagonal and irregular lump-like in shape. They were strongly positive, dark blue, with phosphotungstic acid -haematoxylin (PTAH) stain in all cases examined. Among the human antibodies tested, epithelial membrane antigen (EMA) gave specifically positive immunostainability with ICr in all cases. Annual ring-like lamellar or concentric structures were detected by electron microscopy. Positive staining of ICr with PTAH and anti-EMA antibody is very useful as a diagnostic marker for PCa in human prostatic tissues.", "contents": "Immunohistochemical and ultrastructural studies of intraluminal crystalloids in human prostatic carcinomas. Intraluminal crystalloids (ICr) observed in 19 cases of incidental or invasive human prostatic carcinoma (PCa) and in a case of benign prostatic hyperplasia were examined extensively by immunohistochemistry and electron microscopy. They were brilliantly eosinophilic with haematoxylin and eosin, manifesting needle-like, triangular, rectangular, hexagonal and irregular lump-like in shape. They were strongly positive, dark blue, with phosphotungstic acid -haematoxylin (PTAH) stain in all cases examined. Among the human antibodies tested, epithelial membrane antigen (EMA) gave specifically positive immunostainability with ICr in all cases. Annual ring-like lamellar or concentric structures were detected by electron microscopy. Positive staining of ICr with PTAH and anti-EMA antibody is very useful as a diagnostic marker for PCa in human prostatic tissues."} {"id": "PMID:1280883", "title": "Histopathology of myoepithelial (basocellular) hyperplasias in adenosis and epitheliosis of the breast demonstrated by the reactivity of cytokeratins and S100 protein. An analysis of heterogenic cell proliferations in 90 cases of benign and malignant breast diseases.", "content": "This study on the different types of epithelial hyperplasia in fibrocystic disease was inspired by the observation of myoepithelial (basocellular) hyperplasia identified by strong expression of S100 protein and a weak reaction with antibodies against cytokeratin (KL1) in cells forming solid and acinar buds. The cells do not contain immunohistochemically detectable actin or desmin. Glandular transformation and proliferation give rise to basocellular circumductal adenosis. Normal breast tissue, 51 cases of fibrocystic disease with mild, florid and atypical hyperplasias, 7 fibroadenomas and 20 cases of carcinoma in situ were studied and a semiquantitative analysis revealed basal buds and adenosis in less than 40% of cases of mild hyperplasia and up to 73% in florid hyperplasia. Epitheliosis is characterized by a heterogeneous cell pattern with cells positive for S100 protein in 30-60%, but in small ducts up to 100% with an immediate connection to the basal cell layer were positive. Carcinoma in situ contained very rare tumour cells positive for S100 protein. The cells expressing S100 protein in terminal ducts, in adenosis and epitheliosis showed only some of the characteristics of myoepithelial cells, since they lack immunoreactivity with antibodies against actin. These basal clear cells are interpreted as transitional or indeterminate cells with features of myoepithelial precursor cells, but with the ability to develop basocellular nodular and glandular hyperplasia in the ductulo-lobular units in cases of adenosis and juvenile fibroadenoma.", "contents": "Histopathology of myoepithelial (basocellular) hyperplasias in adenosis and epitheliosis of the breast demonstrated by the reactivity of cytokeratins and S100 protein. An analysis of heterogenic cell proliferations in 90 cases of benign and malignant breast diseases. This study on the different types of epithelial hyperplasia in fibrocystic disease was inspired by the observation of myoepithelial (basocellular) hyperplasia identified by strong expression of S100 protein and a weak reaction with antibodies against cytokeratin (KL1) in cells forming solid and acinar buds. The cells do not contain immunohistochemically detectable actin or desmin. Glandular transformation and proliferation give rise to basocellular circumductal adenosis. Normal breast tissue, 51 cases of fibrocystic disease with mild, florid and atypical hyperplasias, 7 fibroadenomas and 20 cases of carcinoma in situ were studied and a semiquantitative analysis revealed basal buds and adenosis in less than 40% of cases of mild hyperplasia and up to 73% in florid hyperplasia. Epitheliosis is characterized by a heterogeneous cell pattern with cells positive for S100 protein in 30-60%, but in small ducts up to 100% with an immediate connection to the basal cell layer were positive. Carcinoma in situ contained very rare tumour cells positive for S100 protein. The cells expressing S100 protein in terminal ducts, in adenosis and epitheliosis showed only some of the characteristics of myoepithelial cells, since they lack immunoreactivity with antibodies against actin. These basal clear cells are interpreted as transitional or indeterminate cells with features of myoepithelial precursor cells, but with the ability to develop basocellular nodular and glandular hyperplasia in the ductulo-lobular units in cases of adenosis and juvenile fibroadenoma."} {"id": "PMID:1280884", "title": "Activation of collagen type II expression in osteoarthritic and rheumatoid cartilage.", "content": "In situ hybridization and immunohistochemical techniques were applied to investigate gene expression and extracellular deposition of collagen type II in normal, osteoarthritic and rheumatoid human articular cartilage. Normal cartilage showed an essentially even extracellular distribution of type II collagen with poly- and monoclonal antibodies, while only a few cells were positive for alpha 1(II) collagen mRNA. In situ hybridization of osteoarthritic and rheumatoid cartilage, however, showed strong enhancement of type II collagen gene expression; transcripts were observed predominantly in the upper middle zone of the articular cartilage while the upper layer was mostly negative and correlated with a zone of reduced proteoglycan staining. The elevated mRNA levels frequently coincided with pericellular immunostaining for type II collagen, indicative for enhanced synthesis of the protein. In two samples, however, pericellular loss of collagen type II staining was found despite positive cytoplasmic signals with the alpha 1(II) RNA probe, suggesting enhanced collagen destruction. Control hybridization with a probe for 18S rRNA revealed very few negative cells throughout both normal and arthritic cartilage samples, ruling out major cell necrosis in the specimens investigated. Thus, our observations identify sites of activated type II collagen synthesis in osteoarthritic cartilage that were predicted by previous biochemical studies and support the notion that damaged cartilage attempts to restore matrix by enhanced synthesis of its components.", "contents": "Activation of collagen type II expression in osteoarthritic and rheumatoid cartilage. In situ hybridization and immunohistochemical techniques were applied to investigate gene expression and extracellular deposition of collagen type II in normal, osteoarthritic and rheumatoid human articular cartilage. Normal cartilage showed an essentially even extracellular distribution of type II collagen with poly- and monoclonal antibodies, while only a few cells were positive for alpha 1(II) collagen mRNA. In situ hybridization of osteoarthritic and rheumatoid cartilage, however, showed strong enhancement of type II collagen gene expression; transcripts were observed predominantly in the upper middle zone of the articular cartilage while the upper layer was mostly negative and correlated with a zone of reduced proteoglycan staining. The elevated mRNA levels frequently coincided with pericellular immunostaining for type II collagen, indicative for enhanced synthesis of the protein. In two samples, however, pericellular loss of collagen type II staining was found despite positive cytoplasmic signals with the alpha 1(II) RNA probe, suggesting enhanced collagen destruction. Control hybridization with a probe for 18S rRNA revealed very few negative cells throughout both normal and arthritic cartilage samples, ruling out major cell necrosis in the specimens investigated. Thus, our observations identify sites of activated type II collagen synthesis in osteoarthritic cartilage that were predicted by previous biochemical studies and support the notion that damaged cartilage attempts to restore matrix by enhanced synthesis of its components."} {"id": "PMID:1280885", "title": "Dendritic cells in glomerulonephritis.", "content": "Renal biopsies (n = 45) from patients with various forms of glomerulonephritis (GN), comprising mesangial IgA-GN (n = 25), focal glomerular sclerosis (n = 13) and acute GN (n = 7), were examined by double staining immunocytochemistry (APAAP, streptavidin-peroxidase) using unconjugated monoclonal antibodies (Ab) against--(i) the CD1b antigen expressed on dendritic cells (DCs), (ii) the invariant chain (Ii), and (iii) biotin-conjugated Ab against HLA-DR. In normal control kidneys (n = 7) without interstitial inflammation, CD1b-positive DCs were not detected. Glomerular endothelial cells and a few cells in mesangial areas showed double staining with the Ab against HLA-DR in Ii. In GN without active interstitial inflammation (n = 9), CD1b-positive DCs were not found. In biopsies with interstitial inflammation (n = 36) CD1b-positive DCs were found interspersed among other inflammatory cells. In seven of the biopsies showing IgA-GN DCs were seen in the vicinity of those glomeruli that exhibited either crescents or glomerular sclerosis with splitting of Bowman's capsule. In proximal tubular epithelial cells de novo expression of HLA-DR/Ii-chain was only seen when DCs were present. We conclude that in different forms of GN: (i) CD1b-positive DCs play an important role in the development of interstitial inflammation, and (ii) their presence may be related to the de novo coexpression of HLA-DR/Ii in tubular epithelial cells, possibly mediated through the production of interferon gamma and other cytokines.", "contents": "Dendritic cells in glomerulonephritis. Renal biopsies (n = 45) from patients with various forms of glomerulonephritis (GN), comprising mesangial IgA-GN (n = 25), focal glomerular sclerosis (n = 13) and acute GN (n = 7), were examined by double staining immunocytochemistry (APAAP, streptavidin-peroxidase) using unconjugated monoclonal antibodies (Ab) against--(i) the CD1b antigen expressed on dendritic cells (DCs), (ii) the invariant chain (Ii), and (iii) biotin-conjugated Ab against HLA-DR. In normal control kidneys (n = 7) without interstitial inflammation, CD1b-positive DCs were not detected. Glomerular endothelial cells and a few cells in mesangial areas showed double staining with the Ab against HLA-DR in Ii. In GN without active interstitial inflammation (n = 9), CD1b-positive DCs were not found. In biopsies with interstitial inflammation (n = 36) CD1b-positive DCs were found interspersed among other inflammatory cells. In seven of the biopsies showing IgA-GN DCs were seen in the vicinity of those glomeruli that exhibited either crescents or glomerular sclerosis with splitting of Bowman's capsule. In proximal tubular epithelial cells de novo expression of HLA-DR/Ii-chain was only seen when DCs were present. We conclude that in different forms of GN: (i) CD1b-positive DCs play an important role in the development of interstitial inflammation, and (ii) their presence may be related to the de novo coexpression of HLA-DR/Ii in tubular epithelial cells, possibly mediated through the production of interferon gamma and other cytokines."} {"id": "PMID:1280887", "title": "[Specific immune preparations for the prevention and treatment of suppurative-inflammatory diseases of Proteus etiology (a review of the literature)].", "content": "Literature data are analyzed on the possibility of designing vaccines Proteus agents for obtaining specific blood agents. Perspective are designs directed to investigation of the raw material base for obtaining allogenous anti-Proteus blood agents.", "contents": "[Specific immune preparations for the prevention and treatment of suppurative-inflammatory diseases of Proteus etiology (a review of the literature)]. Literature data are analyzed on the possibility of designing vaccines Proteus agents for obtaining specific blood agents. Perspective are designs directed to investigation of the raw material base for obtaining allogenous anti-Proteus blood agents."} {"id": "PMID:1280888", "title": "[A method for the individual choice of anti-arrhythmia preparations in extrasystole].", "content": "Pharmacological analysis of arrhythmogenesis was approved in 60 patients with ventricular extrasystolic arrhythmia (EA). Individual choice of anti-arrhythmia agents (AAA) was realized by successive drug-induced block of slow calcium cancels by isoptin and rapid sodium channel by class I AAA. Changes of arrhythmogenesis were registered electrocardiographically. Acute tests with isoptin revealed a good antiarrhythmic effect in 46.67%, with AAA--in 30%. It is concluded that methods of pharmacological analysis of arrhythmogenesis widely used in experimental cardiology may be used in the clinic for individual choice of AAA.", "contents": "[A method for the individual choice of anti-arrhythmia preparations in extrasystole]. Pharmacological analysis of arrhythmogenesis was approved in 60 patients with ventricular extrasystolic arrhythmia (EA). Individual choice of anti-arrhythmia agents (AAA) was realized by successive drug-induced block of slow calcium cancels by isoptin and rapid sodium channel by class I AAA. Changes of arrhythmogenesis were registered electrocardiographically. Acute tests with isoptin revealed a good antiarrhythmic effect in 46.67%, with AAA--in 30%. It is concluded that methods of pharmacological analysis of arrhythmogenesis widely used in experimental cardiology may be used in the clinic for individual choice of AAA."} {"id": "PMID:1280891", "title": "Comparison of immune responses to a native viral antigen and a synthetic peptide derived from it: implications for vaccine development.", "content": "Murine immune responses to the hepatitis B surface antigen (HBsAg) and a synthetic peptide derived from it were compared at the humoral level. Six of nine strains used responded to either peptide or HBsAg, though restriction profiles were not superimposable. Two of three strains non-responsive to HBsAg produced an antibody response on immunization with peptide which was cross-reactive with both peptide and HBsAg. In in vitro lymphocyte stimulation assays, lymphocyte from all six peptide-immunized mouse strains could be induced to proliferate on challenge with HBsAg. However, of the HBsAg-immunized groups, lymphocytes from only three of six responder strains proliferated on in vitro HBsAg challenge. Cumulatively, these results suggest that a vaccine formulation that includes both protein antigens and synthetic peptides derived from these proteins may be more effective at eliciting an immune response in a broader cross-section of target population.", "contents": "Comparison of immune responses to a native viral antigen and a synthetic peptide derived from it: implications for vaccine development. Murine immune responses to the hepatitis B surface antigen (HBsAg) and a synthetic peptide derived from it were compared at the humoral level. Six of nine strains used responded to either peptide or HBsAg, though restriction profiles were not superimposable. Two of three strains non-responsive to HBsAg produced an antibody response on immunization with peptide which was cross-reactive with both peptide and HBsAg. In in vitro lymphocyte stimulation assays, lymphocyte from all six peptide-immunized mouse strains could be induced to proliferate on challenge with HBsAg. However, of the HBsAg-immunized groups, lymphocytes from only three of six responder strains proliferated on in vitro HBsAg challenge. Cumulatively, these results suggest that a vaccine formulation that includes both protein antigens and synthetic peptides derived from these proteins may be more effective at eliciting an immune response in a broader cross-section of target population."} {"id": "PMID:1280892", "title": "Influence of substance P on gastrointestinal myoelectrical activity in the conscious piglet.", "content": "In conscious piglets with electrodes implanted in the wall of the antrum pylori, the small intestine and the caecum, the influence of intravenous infusion of substance P (SP) (0.1 and 1 micrograms/kg/min for 2 hours) on gastrointestinal myoelectrical activity and arterial pressure was studied. SP was without significant influence on electrical activity of the antrum. However, intestinal myoelectrical activities were significantly stimulated. In the small intestine SP infusion resulted in an increase in frequency of migrating myoelectrical complexes and in irregular spiking activity, resulting in an augmentation of the integrated total activity. In the caecum SP provoked a prolongation of complexes of long spike bursts (LSB) as well as an increase in number of LSB/complex. In the studied doses SP had no significant effect on arterial pressure.", "contents": "Influence of substance P on gastrointestinal myoelectrical activity in the conscious piglet. In conscious piglets with electrodes implanted in the wall of the antrum pylori, the small intestine and the caecum, the influence of intravenous infusion of substance P (SP) (0.1 and 1 micrograms/kg/min for 2 hours) on gastrointestinal myoelectrical activity and arterial pressure was studied. SP was without significant influence on electrical activity of the antrum. However, intestinal myoelectrical activities were significantly stimulated. In the small intestine SP infusion resulted in an increase in frequency of migrating myoelectrical complexes and in irregular spiking activity, resulting in an augmentation of the integrated total activity. In the caecum SP provoked a prolongation of complexes of long spike bursts (LSB) as well as an increase in number of LSB/complex. In the studied doses SP had no significant effect on arterial pressure."} {"id": "PMID:1280890", "title": "Laser therapy of gastrointestinal tumors.", "content": "Surgical resection remains the therapy of choice for the treatment of potentially curable gastrointestinal tract (GI) malignancies. Many of these tumors are incurable at the time of diagnosis and therapy should be directed towards palliation with the intent of minimizing pain, bleeding, obstruction, and potential morbidity. Endoscopic laser therapy is uniquely applicable for the palliation of GI tumors and in selective instances may be appropriate for the treatment of early lesions. Eighty-six patients with GI malignancy have been treated at our institution since 1985. Thirty-one patients had advanced upper GI lesions (esophagus: 26, gastric: 3, duodenal: 1, and pancreatic: 1) and 55 patients had lower GI tumors (colon: 37 and rectal: 18). Pre-resectional recanalization for obstructing colorectal carcinomas obviating initial operative diversion was performed in 31 (56%) of 55 patients. Twenty-four patients had palliative laser therapy (obstruction: 17 and hemorrhage: 7) with resolution of their symptoms. There was 1 laser related perforation in the pre-resectional group and the overall complication rate was 1.2%. Endoscopic Nd:YAG and currently photodynamic laser therapy for GI tumors has proven to be an effective mode of therapy for advanced GI neoplasms with minimal morbidity. The utility of photodynamic therapy for the treatment of early stage esophageal and gastric cancers remains controversial.", "contents": "Laser therapy of gastrointestinal tumors. Surgical resection remains the therapy of choice for the treatment of potentially curable gastrointestinal tract (GI) malignancies. Many of these tumors are incurable at the time of diagnosis and therapy should be directed towards palliation with the intent of minimizing pain, bleeding, obstruction, and potential morbidity. Endoscopic laser therapy is uniquely applicable for the palliation of GI tumors and in selective instances may be appropriate for the treatment of early lesions. Eighty-six patients with GI malignancy have been treated at our institution since 1985. Thirty-one patients had advanced upper GI lesions (esophagus: 26, gastric: 3, duodenal: 1, and pancreatic: 1) and 55 patients had lower GI tumors (colon: 37 and rectal: 18). Pre-resectional recanalization for obstructing colorectal carcinomas obviating initial operative diversion was performed in 31 (56%) of 55 patients. Twenty-four patients had palliative laser therapy (obstruction: 17 and hemorrhage: 7) with resolution of their symptoms. There was 1 laser related perforation in the pre-resectional group and the overall complication rate was 1.2%. Endoscopic Nd:YAG and currently photodynamic laser therapy for GI tumors has proven to be an effective mode of therapy for advanced GI neoplasms with minimal morbidity. The utility of photodynamic therapy for the treatment of early stage esophageal and gastric cancers remains controversial."} {"id": "PMID:1280893", "title": "[The demonstration of recurrent motor axon collaterals in the chick embryo by using horseradish peroxidase axonal transport].", "content": "Motoneurons were labelled by retrograde axonal transport of HRP applied to transected spinal nerves in 9-11-day chick embryos in the in vitro spinal cord preparation. Recurrent motor axon collaterals were revealed in 17 of 48 motor axons which could be followed in the edge regions of labelled motoneuronal pools. The results, coupled with author's earlier electrophysiological data, provide further evidence for the presence of the Renshaw inhibition in the avian spinal cord.", "contents": "[The demonstration of recurrent motor axon collaterals in the chick embryo by using horseradish peroxidase axonal transport]. Motoneurons were labelled by retrograde axonal transport of HRP applied to transected spinal nerves in 9-11-day chick embryos in the in vitro spinal cord preparation. Recurrent motor axon collaterals were revealed in 17 of 48 motor axons which could be followed in the edge regions of labelled motoneuronal pools. The results, coupled with author's earlier electrophysiological data, provide further evidence for the presence of the Renshaw inhibition in the avian spinal cord."} {"id": "PMID:1280894", "title": "[A light microscopic study of the axonal collaterals of the lumbar motoneurons in the spinal cord of the frog Rana ridibunda].", "content": "By using intracellular injection of horseradish peroxidase into the lumbar motoneurones of the isolated spinal cord of the frog Rana ridibunda the structure of axon collaterals was studied. It was shown that about 50% of the HRP-stained cells had mainly one axon collateral of the 1st order. The subsequent branching patterns of the collaterals showed considerable variations. The number of swellings in various collaterals was from 10 up 100. The mean diameter of swellings varied from 0.8 up 10.0 microns. It is believed that the axon collateral swellings from contacts on the dendrites of the nerve cells mainly. Apparent axosomatic contacts were revealed on the motoneurons and small nerve cells. As in the cat, collateral swellings were found on the dendrites of the parent motoneuron. Obtained morphological data the structure of motor axon collaterals in the frog are compared with those in the cat. Functional significance of the axon collateral in the frog is discussed.", "contents": "[A light microscopic study of the axonal collaterals of the lumbar motoneurons in the spinal cord of the frog Rana ridibunda]. By using intracellular injection of horseradish peroxidase into the lumbar motoneurones of the isolated spinal cord of the frog Rana ridibunda the structure of axon collaterals was studied. It was shown that about 50% of the HRP-stained cells had mainly one axon collateral of the 1st order. The subsequent branching patterns of the collaterals showed considerable variations. The number of swellings in various collaterals was from 10 up 100. The mean diameter of swellings varied from 0.8 up 10.0 microns. It is believed that the axon collateral swellings from contacts on the dendrites of the nerve cells mainly. Apparent axosomatic contacts were revealed on the motoneurons and small nerve cells. As in the cat, collateral swellings were found on the dendrites of the parent motoneuron. Obtained morphological data the structure of motor axon collaterals in the frog are compared with those in the cat. Functional significance of the axon collateral in the frog is discussed."} {"id": "PMID:1280895", "title": "[The quantitative morphological characteristics of the neurons of the anterior horns of the spinal cord in the kitten].", "content": "Golgi preparations of cervical part of the spinal cord of 30-day kittens were used to study sparely and densely branching neurons of lamina VII, sparely and densely branching neurons of lamina VIII and big densely branching motor neurons (as classified by Leontovich) of medial and lateral regions of lamina IX. Qualitative morphological characteristics of geometry of each cell type were obtained by the method of computerized morphometry. The details of the structure of neurons belonging to different laminae of grey matter are discussed.", "contents": "[The quantitative morphological characteristics of the neurons of the anterior horns of the spinal cord in the kitten]. Golgi preparations of cervical part of the spinal cord of 30-day kittens were used to study sparely and densely branching neurons of lamina VII, sparely and densely branching neurons of lamina VIII and big densely branching motor neurons (as classified by Leontovich) of medial and lateral regions of lamina IX. Qualitative morphological characteristics of geometry of each cell type were obtained by the method of computerized morphometry. The details of the structure of neurons belonging to different laminae of grey matter are discussed."} {"id": "PMID:1280898", "title": "Personality of patients with Sudeck's atrophy following tibial fracture.", "content": "Patients with reflex sympathetic dystrophy are often considered by physicians and allied health personnel as having a peculiar personality. In medical literature they are frequently described as anxious and depressive, emotional, nervous and irritable patients with neurovegetative instability. A review of the literature on psychological research in this field is not always illuminating. Hypochondria and hysteria, whether or not accompanied by depression, are frequently reported to be typical traits, whereas other findings point more in the direction of psychosis. Increased anxiety, emotional lability and lowered self-esteem are psychological entities that are regularly encountered. The present study includes 42 cases of severe reflex sympathetic dystrophy. Except for the 7 cases of Sudeck atrophy of the hand and wrist, the localization was always in the foot or ankle. The majority of patients had a history of fractures or orthopedic procedures on the lower limbs as a causative factor. In addition to an interview, two questionnaires and a projective test (Rorschach) were used in the personality assessment. While the Rorschach test did not reveal any findings that could be considered as typical of our study population, we did observe different frequency distributions for the personality traits \"self-satisfaction\", \"rigidity\" and \"somatization\".", "contents": "Personality of patients with Sudeck's atrophy following tibial fracture. Patients with reflex sympathetic dystrophy are often considered by physicians and allied health personnel as having a peculiar personality. In medical literature they are frequently described as anxious and depressive, emotional, nervous and irritable patients with neurovegetative instability. A review of the literature on psychological research in this field is not always illuminating. Hypochondria and hysteria, whether or not accompanied by depression, are frequently reported to be typical traits, whereas other findings point more in the direction of psychosis. Increased anxiety, emotional lability and lowered self-esteem are psychological entities that are regularly encountered. The present study includes 42 cases of severe reflex sympathetic dystrophy. Except for the 7 cases of Sudeck atrophy of the hand and wrist, the localization was always in the foot or ankle. The majority of patients had a history of fractures or orthopedic procedures on the lower limbs as a causative factor. In addition to an interview, two questionnaires and a projective test (Rorschach) were used in the personality assessment. While the Rorschach test did not reveal any findings that could be considered as typical of our study population, we did observe different frequency distributions for the personality traits \"self-satisfaction\", \"rigidity\" and \"somatization\"."} {"id": "PMID:1280896", "title": "[The quantitative morphological characteristics of the spinal neurons in the kitten developing under conditions of limited afferent input].", "content": "Golgi preparations of cervical part of the spinal cord were used to study sparely and densely branching neurons of lamina VII, sparely and densely branching neurons of lamina VIII and large densely branching motor neurons of lamina IX in 30-day kittens developing under the conditions of limited reticulospinal input. Limitation was induced by electrocoagulation of bulbar magnocellular nucleus and caudal reticular pontine nucleus performed at the 7th day. Computerized morphometry revealed that partial deafferentation affects the geometry in all studied cell types except densely branching neurons of lamina VIII. Adaptive nature of structural reorganization of spinal neurons and possible relationship between morphological properties and functional profile of cells are discussed.", "contents": "[The quantitative morphological characteristics of the spinal neurons in the kitten developing under conditions of limited afferent input]. Golgi preparations of cervical part of the spinal cord were used to study sparely and densely branching neurons of lamina VII, sparely and densely branching neurons of lamina VIII and large densely branching motor neurons of lamina IX in 30-day kittens developing under the conditions of limited reticulospinal input. Limitation was induced by electrocoagulation of bulbar magnocellular nucleus and caudal reticular pontine nucleus performed at the 7th day. Computerized morphometry revealed that partial deafferentation affects the geometry in all studied cell types except densely branching neurons of lamina VIII. Adaptive nature of structural reorganization of spinal neurons and possible relationship between morphological properties and functional profile of cells are discussed."} {"id": "PMID:1280899", "title": "Mercury deposition and its relationship to inner ear function in methylmercury-poisoned rats. A histological and immunohistochemical study.", "content": "Mercury deposition and its relationship to the inner ear function in methylmercury-poisoned rats were examined. Rats were poisoned with methylmercury chloride. After the appearance of signs of poisoning, the cerebellar and inner ear tissues were examined histochemically using an autoradiographic procedure. Mercury deposits were typically found in the cerebellum and appeared in parts of the vestibular nerves, cochlear nerves, spiral ganglion and stria vascularis. In the vestibule, a slight mercury deposition was observed in the acoustic maculae and in the cochlea; only one instance of mercury deposit in the organ of Corti was detected. The effect of mercury on the inner ear function was also assessed on the basis of immunohistochemical localization of substance P which is believed to be a neurotransmitter in the inner ear. However, no pathological changes were detected. These findings suggest that methylmercury deposition has little effect on the inner ear function.", "contents": "Mercury deposition and its relationship to inner ear function in methylmercury-poisoned rats. A histological and immunohistochemical study. Mercury deposition and its relationship to the inner ear function in methylmercury-poisoned rats were examined. Rats were poisoned with methylmercury chloride. After the appearance of signs of poisoning, the cerebellar and inner ear tissues were examined histochemically using an autoradiographic procedure. Mercury deposits were typically found in the cerebellum and appeared in parts of the vestibular nerves, cochlear nerves, spiral ganglion and stria vascularis. In the vestibule, a slight mercury deposition was observed in the acoustic maculae and in the cochlea; only one instance of mercury deposit in the organ of Corti was detected. The effect of mercury on the inner ear function was also assessed on the basis of immunohistochemical localization of substance P which is believed to be a neurotransmitter in the inner ear. However, no pathological changes were detected. These findings suggest that methylmercury deposition has little effect on the inner ear function."} {"id": "PMID:1280900", "title": "Inhibitory effects of tetramethylpyrazine on platelets during cardiopulmonary bypass and arterial thrombus formation in dogs.", "content": "The corrected platelet count at the end of cardiopulmonary bypass (CPB) in nontreated dogs fell to 56.7% of the pre-operative level, while in tetramethylpyrazine (TMP, 10 mg.kg-1, iv)-treated dogs it fell to 82.8%. The number of alpha-granule membrane protein (GMP-140) which was expressed on the surface of activated platelets increased from the outset of CPB and reached the peak at the end of CPB in control dogs. But the number of GMP-140 molecules did not increase significantly throughout the operative procedure in TMP-treated dogs. In experimental thrombosis in dogs, the weight of the thrombus reduced to 23% of that in controls and the radioactivity ratio between the thrombus and blood was only 29% of that in controls at 4 h after iv injection of 125I-SZ-51 (a monoclonal antibody against GMP-140). These results indicate that TMP inhibits the platelet activation during CPB and arterial thrombosis.", "contents": "Inhibitory effects of tetramethylpyrazine on platelets during cardiopulmonary bypass and arterial thrombus formation in dogs. The corrected platelet count at the end of cardiopulmonary bypass (CPB) in nontreated dogs fell to 56.7% of the pre-operative level, while in tetramethylpyrazine (TMP, 10 mg.kg-1, iv)-treated dogs it fell to 82.8%. The number of alpha-granule membrane protein (GMP-140) which was expressed on the surface of activated platelets increased from the outset of CPB and reached the peak at the end of CPB in control dogs. But the number of GMP-140 molecules did not increase significantly throughout the operative procedure in TMP-treated dogs. In experimental thrombosis in dogs, the weight of the thrombus reduced to 23% of that in controls and the radioactivity ratio between the thrombus and blood was only 29% of that in controls at 4 h after iv injection of 125I-SZ-51 (a monoclonal antibody against GMP-140). These results indicate that TMP inhibits the platelet activation during CPB and arterial thrombosis."} {"id": "PMID:1280901", "title": "Expression of helix-loop-helix regulatory genes during differentiation of mouse osteoblastic cells.", "content": "Although much is known about the hormonal regulation of osteoblastic cell differentiation, much less is known about the nuclear regulatory molecules that affect this process. We analyzed the expression of several regulatory molecules of the helix-loop-helix (H-L-H) group in primary mouse calvarial cells and in MC3T3-E1 mouse osteoblastic cells in situations representing different degrees of cellular differentiation. H-L-H class regulators are known to participate directly in directing cell fate and differentiation decisions in other mesodermal lineages. Two of the molecules that we studied, Id and E12, have well-established roles in this process. The other, mTwi, the murine homolog of the Drosophila twist gene, is a newly cloned mammalian H-L-H gene. Levels of E12 RNA remained unchanged during differentiation. On the other hand, in both primary osteoblastic cells and MC3T3-E1 cells, the abundance of Id and mTwi declined with cell maturation; mTwi less dramatically than Id. That Id expression is causally related to differentiation is suggested by the finding that MC3T3-E1 cells transfected with an Id-expression plasmid fail to undergo differentiation. We conclude that helix-loop-helix regulatory genes are expressed in mouse osteoblastic cells, where they are likely to participate in differentiation. The E12 gene product is likely to function as a positive modulating factor. In contrast, Id inhibits differentiation, probably by sequestering other H-L-H gene regulators, including E12, in inactive complexes. The precise role of mTwi is more speculative at this time, but the observed pattern of expression is consistent with a role in early and midmesodermal specification that is terminated as cells differentiate.", "contents": "Expression of helix-loop-helix regulatory genes during differentiation of mouse osteoblastic cells. Although much is known about the hormonal regulation of osteoblastic cell differentiation, much less is known about the nuclear regulatory molecules that affect this process. We analyzed the expression of several regulatory molecules of the helix-loop-helix (H-L-H) group in primary mouse calvarial cells and in MC3T3-E1 mouse osteoblastic cells in situations representing different degrees of cellular differentiation. H-L-H class regulators are known to participate directly in directing cell fate and differentiation decisions in other mesodermal lineages. Two of the molecules that we studied, Id and E12, have well-established roles in this process. The other, mTwi, the murine homolog of the Drosophila twist gene, is a newly cloned mammalian H-L-H gene. Levels of E12 RNA remained unchanged during differentiation. On the other hand, in both primary osteoblastic cells and MC3T3-E1 cells, the abundance of Id and mTwi declined with cell maturation; mTwi less dramatically than Id. That Id expression is causally related to differentiation is suggested by the finding that MC3T3-E1 cells transfected with an Id-expression plasmid fail to undergo differentiation. We conclude that helix-loop-helix regulatory genes are expressed in mouse osteoblastic cells, where they are likely to participate in differentiation. The E12 gene product is likely to function as a positive modulating factor. In contrast, Id inhibits differentiation, probably by sequestering other H-L-H gene regulators, including E12, in inactive complexes. The precise role of mTwi is more speculative at this time, but the observed pattern of expression is consistent with a role in early and midmesodermal specification that is terminated as cells differentiate."} {"id": "PMID:1280902", "title": "Release of oxygen radicals by articular chondrocytes: a study of luminol-dependent chemiluminescence and hydrogen peroxide secretion.", "content": "We previously established that normal articular chondrocytes, like macrophages, express class II major histocompatibility antigens, present antigen, and induce mixed and autologous lymphocyte stimulation. In a recent study using the trapped indicator 2',7'-dichlorofluorescein diacetate, we were able to measure levels of intracellular hydrogen peroxide within normal articular chondrocytes (J Immunol 245:690-696, 1990). In the present study, we utilized the technique of chemiluminescence and the biochemical method of quantitating hydrogen peroxide release to measure the production of reactive oxygen intermediates by articular chondrocytes. Chondrocytes, in suspension or adherent to coverslips, showed luminol-dependent chemiluminescence that was dependent on the number and viability of cells. There was a dose-dependent increase in chemiluminescence in response to soluble stimuli, such as phorbol myristate acetate (PMA), concanavalin A (ConA), and f-Met-Leu-Phe (FMLP). Azide inhibited chemiluminescence, suggesting that the light emission in chondrocytes is myeloperoxidase dependent. The antioxidant, catalase, inhibited chemiluminescence but superoxide dismutase had no effect, suggesting that luminol-dependent chemiluminescence in chondrocytes mostly measured hydrogen peroxide. Chemiluminescence was also observed in fragments of live cartilage tissue, indicating that chondrocytes that are cartilage matrix bound can generate the respiratory burst response. Using the scopoletin oxidation assay, we confirmed the release of increasing amounts of hydrogen peroxide by chondrocytes exposed to interleukin-1, rabbit interferon, and tumor necrosis factor alpha. Tumor necrosis factor alpha had both priming and enhancing effects on reactive oxygen intermediate production by chondrocytes. Reactive oxygen intermediates have been shown to play a significant role in matrix degradation. We suggest that reactive oxygen intermediates produced by chondrocytes play an important role in the degradation of matrix in arthritis.", "contents": "Release of oxygen radicals by articular chondrocytes: a study of luminol-dependent chemiluminescence and hydrogen peroxide secretion. We previously established that normal articular chondrocytes, like macrophages, express class II major histocompatibility antigens, present antigen, and induce mixed and autologous lymphocyte stimulation. In a recent study using the trapped indicator 2',7'-dichlorofluorescein diacetate, we were able to measure levels of intracellular hydrogen peroxide within normal articular chondrocytes (J Immunol 245:690-696, 1990). In the present study, we utilized the technique of chemiluminescence and the biochemical method of quantitating hydrogen peroxide release to measure the production of reactive oxygen intermediates by articular chondrocytes. Chondrocytes, in suspension or adherent to coverslips, showed luminol-dependent chemiluminescence that was dependent on the number and viability of cells. There was a dose-dependent increase in chemiluminescence in response to soluble stimuli, such as phorbol myristate acetate (PMA), concanavalin A (ConA), and f-Met-Leu-Phe (FMLP). Azide inhibited chemiluminescence, suggesting that the light emission in chondrocytes is myeloperoxidase dependent. The antioxidant, catalase, inhibited chemiluminescence but superoxide dismutase had no effect, suggesting that luminol-dependent chemiluminescence in chondrocytes mostly measured hydrogen peroxide. Chemiluminescence was also observed in fragments of live cartilage tissue, indicating that chondrocytes that are cartilage matrix bound can generate the respiratory burst response. Using the scopoletin oxidation assay, we confirmed the release of increasing amounts of hydrogen peroxide by chondrocytes exposed to interleukin-1, rabbit interferon, and tumor necrosis factor alpha. Tumor necrosis factor alpha had both priming and enhancing effects on reactive oxygen intermediate production by chondrocytes. Reactive oxygen intermediates have been shown to play a significant role in matrix degradation. We suggest that reactive oxygen intermediates produced by chondrocytes play an important role in the degradation of matrix in arthritis."} {"id": "PMID:1280903", "title": "Prostaglandin E2 stimulates synthesis of insulin-like growth factor binding protein-3 in rat bone cells in vitro.", "content": "Prostaglandin E2 is produced by bone cells and increases cyclic AMP in these cells. Like PTH and dibutyryl cyclic AMP, PGE2 is a potent stimulator of IGF-I synthesis in cultured rat osteoblasts and inhibits DNA synthesis and type I procollagen gene expression. In addition, PGE2 inhibits the response of the cells toward IGF-I after 1 day but not after 4 days of incubation. Rat calvaria osteoblasts constitutively release IGFBPs into the culture medium, in particular IGFBP-2 and IGFBP-3. Like growth hormone, PGE2 stimulates the accumulation of IGFBP-3. PGE2 rapidly increases IGF-I and IGFBP-3 mRNA expression in calvaria cells, with a time course clearly different from that observed in response to growth hormone. Thus, PGE2 modifies not only the synthesis of IGF-I but also that of IGFBP-3 in skeletal tissue.", "contents": "Prostaglandin E2 stimulates synthesis of insulin-like growth factor binding protein-3 in rat bone cells in vitro. Prostaglandin E2 is produced by bone cells and increases cyclic AMP in these cells. Like PTH and dibutyryl cyclic AMP, PGE2 is a potent stimulator of IGF-I synthesis in cultured rat osteoblasts and inhibits DNA synthesis and type I procollagen gene expression. In addition, PGE2 inhibits the response of the cells toward IGF-I after 1 day but not after 4 days of incubation. Rat calvaria osteoblasts constitutively release IGFBPs into the culture medium, in particular IGFBP-2 and IGFBP-3. Like growth hormone, PGE2 stimulates the accumulation of IGFBP-3. PGE2 rapidly increases IGF-I and IGFBP-3 mRNA expression in calvaria cells, with a time course clearly different from that observed in response to growth hormone. Thus, PGE2 modifies not only the synthesis of IGF-I but also that of IGFBP-3 in skeletal tissue."} {"id": "PMID:1280905", "title": "Influence of protein kinase C, cAMP and phosphatase activity on histamine release produced by compound 48/80 and sodium fluoride on rat mast cells.", "content": "We have studied the effect of protein kinase C and protein kinase A activation, and phosphatase inhibition on two different stimuli with distinct mechanisms of action. The first stimulus is compound 48/80, and its action is mediated probably by a Gi-protein, while the other is sodium fluoride, which unspecifically activates G-proteins. We established a comparative study because the action of compound 48/80 is calcium-independent, while fluoride is strictly calcium-dependent. The activation of protein kinase C was attained with the phorbol esther 12-O-tetradecanoylphorbol-13-acetate, protein kinase A was activated by increasing cAMP levels with forskolin or rolipram, and the phosphatase activity was inhibited with okadaic acid (OA), which inhibits phosphatases type 1 and 2A. Our results show that OA enhances the response to fluoride and compound 48/80 in the absence of calcium, and we conclude that calcium has a negative feedback role on the cell response. Protein kinase A activation strongly inhibits the response to fluoride, and the results show a positive regulation of protein kinase C and a negative regulation of protein kinase A over fluoride response. As previously reported by other authors for the ionophore A23187, TPA notably potentiates the response to fluoride, which supports its possible modulatory role on extracellular calcium-dependent stimuli.", "contents": "Influence of protein kinase C, cAMP and phosphatase activity on histamine release produced by compound 48/80 and sodium fluoride on rat mast cells. We have studied the effect of protein kinase C and protein kinase A activation, and phosphatase inhibition on two different stimuli with distinct mechanisms of action. The first stimulus is compound 48/80, and its action is mediated probably by a Gi-protein, while the other is sodium fluoride, which unspecifically activates G-proteins. We established a comparative study because the action of compound 48/80 is calcium-independent, while fluoride is strictly calcium-dependent. The activation of protein kinase C was attained with the phorbol esther 12-O-tetradecanoylphorbol-13-acetate, protein kinase A was activated by increasing cAMP levels with forskolin or rolipram, and the phosphatase activity was inhibited with okadaic acid (OA), which inhibits phosphatases type 1 and 2A. Our results show that OA enhances the response to fluoride and compound 48/80 in the absence of calcium, and we conclude that calcium has a negative feedback role on the cell response. Protein kinase A activation strongly inhibits the response to fluoride, and the results show a positive regulation of protein kinase C and a negative regulation of protein kinase A over fluoride response. As previously reported by other authors for the ionophore A23187, TPA notably potentiates the response to fluoride, which supports its possible modulatory role on extracellular calcium-dependent stimuli."} {"id": "PMID:1280906", "title": "Ionic regulation of human basophil releasability. I. Inhibitory effect of copper.", "content": "The effects of copper (CuSO4 and CuCl2) on in vitro histamine release from human basophils stimulated by anti-IgE and Ca2+ ionophore A23187 were evaluated. Both CuSO4 and CuCl2 caused a dose-related inhibition of histamine release, which was more pronounced on anti-IgE- than on Ca2+ ionophore-induced histamine release. The concentration which produced 50% inhibition of anti-IgE-induced histamine release was 1.3 microM for CuSO4 and 1.5 microM for CuCl2; the maximal inhibition of Ca2+ ionophore-induced histamine release was 33% for CuCl2 (4 microM) and 51% for CuSO4 (16 microM). The inhibitory effect on anti-IgE-induced histamine release persisted also when extracellular Cu2+ was removed by cell washing before stimulation, whereas no inhibition of Ca2+ ionophore-induced histamine release was found when extracellular Cu2+ was removed. The activity of Cu2+ was independent of any effects of deuterium oxide and colchicine, two agents known to interact with microtubules. Increased extracellular Ca2+ concentrations reduced the inhibitory effect of CuCl2 on Ca2+ ionophore-induced histamine release, and Schild plot analysis demonstrated that Cu2+ ions are competitive antagonists of Ca2+ ions. These results indicate that Cu2+ ions in the micromolar range down-regulate anti-IgE- and Ca2+ ionophore-induced histamine release. Since Cu2+ concentration in human plasma is in the micromolar range (30 microM with 10-30% of free Cu2+), it is conceivable that Cu2+ ions contribute to the in vivo regulation of histamine release from human basophils.", "contents": "Ionic regulation of human basophil releasability. I. Inhibitory effect of copper. The effects of copper (CuSO4 and CuCl2) on in vitro histamine release from human basophils stimulated by anti-IgE and Ca2+ ionophore A23187 were evaluated. Both CuSO4 and CuCl2 caused a dose-related inhibition of histamine release, which was more pronounced on anti-IgE- than on Ca2+ ionophore-induced histamine release. The concentration which produced 50% inhibition of anti-IgE-induced histamine release was 1.3 microM for CuSO4 and 1.5 microM for CuCl2; the maximal inhibition of Ca2+ ionophore-induced histamine release was 33% for CuCl2 (4 microM) and 51% for CuSO4 (16 microM). The inhibitory effect on anti-IgE-induced histamine release persisted also when extracellular Cu2+ was removed by cell washing before stimulation, whereas no inhibition of Ca2+ ionophore-induced histamine release was found when extracellular Cu2+ was removed. The activity of Cu2+ was independent of any effects of deuterium oxide and colchicine, two agents known to interact with microtubules. Increased extracellular Ca2+ concentrations reduced the inhibitory effect of CuCl2 on Ca2+ ionophore-induced histamine release, and Schild plot analysis demonstrated that Cu2+ ions are competitive antagonists of Ca2+ ions. These results indicate that Cu2+ ions in the micromolar range down-regulate anti-IgE- and Ca2+ ionophore-induced histamine release. Since Cu2+ concentration in human plasma is in the micromolar range (30 microM with 10-30% of free Cu2+), it is conceivable that Cu2+ ions contribute to the in vivo regulation of histamine release from human basophils."} {"id": "PMID:1280907", "title": "Actions and cross-reactivity of antiallergic agents and a calcium channel antagonist on rat peritoneal mast cells. Difference in the action mechanisms and cross-reactivity among the agents.", "content": "The actions of the antiallergic agents, disodium chromoglycate (DSCG), tranilast and ketotifen, and of a calcium channel antagonist, nicardipine, and cross-reactivity among the agents were examined by observing the inhibition of 45Ca uptake and histamine release in rat mast cells stimulated by antigen and compound 48/80 (comp. 48/80). 1) All agents inhibited 45Ca uptake and histamine release in mast cells stimulated by antigen. The inhibition of 45Ca uptake by the antiallergic agents paralleled the inhibition of histamine release, while nicardipine inhibition of 45Ca uptake was stronger than its inhibition of histamine release. 2) The action of DSCG on 45Ca uptake and histamine release was significantly decreased in cells stimulated with antigen and phosphatidylserine (PS), while tranilast inhibition of histamine release was not affected by the addition of PS despite a significant decrease in the inhibition of 45Ca uptake. 3) The inhibitory effect of DSCG and tranilast was significantly lower in mast cells stimulated by comp. 48/80 than in the cells stimulated by antigen. 4) Tachyphylaxis was observed in cells re-exposed to DSCG and tranilast following previous exposure to the agents. 5) Cross-reactivity was found between DSCG and tranilast.", "contents": "Actions and cross-reactivity of antiallergic agents and a calcium channel antagonist on rat peritoneal mast cells. Difference in the action mechanisms and cross-reactivity among the agents. The actions of the antiallergic agents, disodium chromoglycate (DSCG), tranilast and ketotifen, and of a calcium channel antagonist, nicardipine, and cross-reactivity among the agents were examined by observing the inhibition of 45Ca uptake and histamine release in rat mast cells stimulated by antigen and compound 48/80 (comp. 48/80). 1) All agents inhibited 45Ca uptake and histamine release in mast cells stimulated by antigen. The inhibition of 45Ca uptake by the antiallergic agents paralleled the inhibition of histamine release, while nicardipine inhibition of 45Ca uptake was stronger than its inhibition of histamine release. 2) The action of DSCG on 45Ca uptake and histamine release was significantly decreased in cells stimulated with antigen and phosphatidylserine (PS), while tranilast inhibition of histamine release was not affected by the addition of PS despite a significant decrease in the inhibition of 45Ca uptake. 3) The inhibitory effect of DSCG and tranilast was significantly lower in mast cells stimulated by comp. 48/80 than in the cells stimulated by antigen. 4) Tachyphylaxis was observed in cells re-exposed to DSCG and tranilast following previous exposure to the agents. 5) Cross-reactivity was found between DSCG and tranilast."} {"id": "PMID:1280908", "title": "Case report: granulocyte colony-stimulating factor overcomes severe neutropenia of large granular lymphocytosis.", "content": "Large granular lymphocytosis (LGL) is characterized by enhanced proliferation of T lymphocytes that have antibody-dependent cell-mediated cytotoxicity or natural killer cell activity and that often produce severe cytopenias, including neutropenia. When a 68-year-old man with seropositive rheumatoid arthritis and severe neutropenia was examined, he was found to have LGL with a T cell gene rearrangement, indicating the presence of a clonal population of T lymphocytes. The patient was admitted with a fever of 102 degrees F and a nonhealing ulcer over the right tibia. When the infection did not respond to intravenous antibiotics, granulocyte colony-stimulating factor (GCSF) therapy was started at 5 micrograms/kg subcutaneously each day. The neutrophil count promptly increased and the patient subsequently defervesced and was able to have a skin graft placed, which healed without difficulty. GCSF, which is known to be an effective therapeutic agent for neutropenia associated with chemotherapy and bone marrow transplantation, also was a very valuable treatment for the life-threatening neutropenia of LGL.", "contents": "Case report: granulocyte colony-stimulating factor overcomes severe neutropenia of large granular lymphocytosis. Large granular lymphocytosis (LGL) is characterized by enhanced proliferation of T lymphocytes that have antibody-dependent cell-mediated cytotoxicity or natural killer cell activity and that often produce severe cytopenias, including neutropenia. When a 68-year-old man with seropositive rheumatoid arthritis and severe neutropenia was examined, he was found to have LGL with a T cell gene rearrangement, indicating the presence of a clonal population of T lymphocytes. The patient was admitted with a fever of 102 degrees F and a nonhealing ulcer over the right tibia. When the infection did not respond to intravenous antibiotics, granulocyte colony-stimulating factor (GCSF) therapy was started at 5 micrograms/kg subcutaneously each day. The neutrophil count promptly increased and the patient subsequently defervesced and was able to have a skin graft placed, which healed without difficulty. GCSF, which is known to be an effective therapeutic agent for neutropenia associated with chemotherapy and bone marrow transplantation, also was a very valuable treatment for the life-threatening neutropenia of LGL."} {"id": "PMID:1280909", "title": "Deletion (14) (q24.3q32.1): evidence for a distinct clinical phenotype.", "content": "We report on a 4-year-old girl with distinctive facial features (redundant skin, bushy eyebrows, narrow palpebral fissures, short, upturned nose, epicanthal folds, and a long upper lip with well-defined philtrum) who has an interstitial deletion of chromosome 14 including band 14q31, designated as 46,XX,del(14)(pter-->q24.3::q32.1-->qter). Comparison with previously reported patients with deletions of 14q involving band 14q31 suggests that there is a distinctive clinical phenotype associated with this deletion. Our patient had dental abnormalities (3 maxillary and 3 mandibular incisors) not described in the other patients.", "contents": "Deletion (14) (q24.3q32.1): evidence for a distinct clinical phenotype. We report on a 4-year-old girl with distinctive facial features (redundant skin, bushy eyebrows, narrow palpebral fissures, short, upturned nose, epicanthal folds, and a long upper lip with well-defined philtrum) who has an interstitial deletion of chromosome 14 including band 14q31, designated as 46,XX,del(14)(pter-->q24.3::q32.1-->qter). Comparison with previously reported patients with deletions of 14q involving band 14q31 suggests that there is a distinctive clinical phenotype associated with this deletion. Our patient had dental abnormalities (3 maxillary and 3 mandibular incisors) not described in the other patients."} {"id": "PMID:1280911", "title": "A role of autoimmunity in the etiopathogenesis of Landau-Kleffner syndrome?", "content": "Four children, 3 boys and 1 girl, with the syndrome of acquired aphasia Landau-Kleffner were followed up during the last 10 years. In 3 children an episodic form of the disease with a good response to corticosteroid treatment and with a favourable prognosis was observed. In the other 1 no improvement of speech function was observed and also epileptic fits were reduced only with difficulty. A positive autoimmune reaction to central (MOZAN) and peripheral (LISAN) myelin was observed repeatedly during the attacks of clinical worsening. On the contrary, during the periods of improvement of language disturbances during the treatment with corticosteroids this hypersensitivity to central as well as peripheral myelin disappeared. Possible changes in myelinization and the role of autoimmune reactions in the etiopathogenesis of the disease are discussed.", "contents": "A role of autoimmunity in the etiopathogenesis of Landau-Kleffner syndrome? Four children, 3 boys and 1 girl, with the syndrome of acquired aphasia Landau-Kleffner were followed up during the last 10 years. In 3 children an episodic form of the disease with a good response to corticosteroid treatment and with a favourable prognosis was observed. In the other 1 no improvement of speech function was observed and also epileptic fits were reduced only with difficulty. A positive autoimmune reaction to central (MOZAN) and peripheral (LISAN) myelin was observed repeatedly during the attacks of clinical worsening. On the contrary, during the periods of improvement of language disturbances during the treatment with corticosteroids this hypersensitivity to central as well as peripheral myelin disappeared. Possible changes in myelinization and the role of autoimmune reactions in the etiopathogenesis of the disease are discussed."} {"id": "PMID:1280910", "title": "Microscopic histopathology of chronic refractory lateral epicondylitis.", "content": "The histopathologic features from 11 patients who were treated surgically for lateral epicondylitis were graded and compared to similar tissue from 12 cadaveric specimens. All studies were done by a single pathologist who had no knowledge of the origin of the specimen. The surgical specimens were interpreted as abnormal in all 11 specimens, and all 12 of the control specimens were reported as being without histologic abnormality. Vascular proliferation was present in 10 of 11 and focal hyaline degeneration was recorded in all 11 of the surgical specimens. Neither feature was present in any of the control material (P < 0.001). These data suggest that chronic refractory lateral epicondylitis requiring surgery is a degenerative rather than inflammatory process. This may account for the lack of response to rest and antiinflammatory medication.", "contents": "Microscopic histopathology of chronic refractory lateral epicondylitis. The histopathologic features from 11 patients who were treated surgically for lateral epicondylitis were graded and compared to similar tissue from 12 cadaveric specimens. All studies were done by a single pathologist who had no knowledge of the origin of the specimen. The surgical specimens were interpreted as abnormal in all 11 specimens, and all 12 of the control specimens were reported as being without histologic abnormality. Vascular proliferation was present in 10 of 11 and focal hyaline degeneration was recorded in all 11 of the surgical specimens. Neither feature was present in any of the control material (P < 0.001). These data suggest that chronic refractory lateral epicondylitis requiring surgery is a degenerative rather than inflammatory process. This may account for the lack of response to rest and antiinflammatory medication."} {"id": "PMID:1280913", "title": "Growth and development in white patients with sickle cell diseases.", "content": "We have evaluated height, weight, bone age, somatomedin-C levels, and pubertal development in 114 Sicilian patients affected by sickle cell diseases (SCDs). Thirty-one had homozygous sickle hemoglobin (SS), 55 S-beta 0 thalassemia, and 28 S-beta + thalassemia. In both children and adults, the mean height and weight were approximately 1 SD below the normal mean for age. The height was below the normal range only in a few subjects (8 children and 4 adult women). Somatomedin-C levels were within the normal range in most of the patients (37/44 children and 17/22 adults). Bone age revealed a slight delay in skeletal maturation (mean chronological age and bone age were 7.7 +/- 3 and 7.11 +/- 2.9 respectively; p < 0.05). Mean age at menarche was increased compared to normal subjects. Our findings show that Sicilian patients with SCD exhibit a moderate delay of growth and adolescence but attain a final height within the normal range.", "contents": "Growth and development in white patients with sickle cell diseases. We have evaluated height, weight, bone age, somatomedin-C levels, and pubertal development in 114 Sicilian patients affected by sickle cell diseases (SCDs). Thirty-one had homozygous sickle hemoglobin (SS), 55 S-beta 0 thalassemia, and 28 S-beta + thalassemia. In both children and adults, the mean height and weight were approximately 1 SD below the normal mean for age. The height was below the normal range only in a few subjects (8 children and 4 adult women). Somatomedin-C levels were within the normal range in most of the patients (37/44 children and 17/22 adults). Bone age revealed a slight delay in skeletal maturation (mean chronological age and bone age were 7.7 +/- 3 and 7.11 +/- 2.9 respectively; p < 0.05). Mean age at menarche was increased compared to normal subjects. Our findings show that Sicilian patients with SCD exhibit a moderate delay of growth and adolescence but attain a final height within the normal range."} {"id": "PMID:1280914", "title": "A cystic partially differentiated nephroblastoma producing alpha-fetoprotein.", "content": "A case of cystic partially differentiated nephroblastoma with immunohistochemical and serological demonstration of alpha-fetoprotein (AFP) production is described. To our knowledge, this is the first such case reported. The morphological heterogeneity of this rare tumor led us to describe the criteria of its nosological classification and of its differential diagnosis with intrarenal teratoma. AFP, besides being a marker of germline-derived tumor, was associated to this rare variant of Wilm's tumor. Although the tumor did not show regression either on clinical or pathologic assessments, serum AFP levels decreased after preoperative chemotherapy and returned to normal limits after nephrectomy.", "contents": "A cystic partially differentiated nephroblastoma producing alpha-fetoprotein. A case of cystic partially differentiated nephroblastoma with immunohistochemical and serological demonstration of alpha-fetoprotein (AFP) production is described. To our knowledge, this is the first such case reported. The morphological heterogeneity of this rare tumor led us to describe the criteria of its nosological classification and of its differential diagnosis with intrarenal teratoma. AFP, besides being a marker of germline-derived tumor, was associated to this rare variant of Wilm's tumor. Although the tumor did not show regression either on clinical or pathologic assessments, serum AFP levels decreased after preoperative chemotherapy and returned to normal limits after nephrectomy."} {"id": "PMID:1280915", "title": "Human basophil histamine release is differently affected by inhibitors of calmodulin, diacylglycerol kinase and peptidyl prolyl cis-trans isomerase in a secretagogue specific manner.", "content": "To assess the role of calmodulin in human basophil histamine release, we triggered leukocytes with different secretagogues in the presence of putative inhibitors of calmodulin. Calcium ionophore-induced histamine release was reduced or blocked by calmidazolium, CGS 9343B, felodipine, metofenazate, and Ro 22-4839. H 186/86, a felodipine-related dihydropyridine derivative, blocked A23187-but not ionomycin-triggered histamine release, suggesting a difference in the mode of action of these ionophores. In contrast, leukocyte histamine release triggered by the purported protein kinase C (PKC) activator, 1,2-isopropylidene-3-decanoyl-sn-glycerol (IpOCOC9), was enhanced by calmidazolium, CGS 9349B and metofenazate but not affected by felodipine or Ro 22-4839, whereas the response triggered by 4 beta-phorbol 12-myristate 13-acetate (PMA) was reduced by metofenazate and Ro 22-4839 but not consistently affected by calmidazolium, CGS 9343B or felodipine. The PMA-induced histamine release was enhanced by H 186/86. Anti-IgE- and FMLP-induced responses were either unaffected or slightly enhanced by the examined calmodulin antagonists. In comparison with the calmodulin antagonists, R 59022, an inhibitor of diacylglycerol kinase, failed to reduce calcium ionophore-triggered histamine release, whereas FK506, an inhibitor of peptidyl prolyl cis-trans isomerase (PPI), reduced both anti-IgE- and ionophore-triggered responses. These results indicate that calmodulin constitutes an obligate link in signal transduction pathways leading to human leukocyte histamine release if the trigger is a calcium ionophore but not when responses are induced by anti-IgE, FMLP or PMA; a calmodulin-dependent component may rather balance responses induced by IpOCOC9.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Human basophil histamine release is differently affected by inhibitors of calmodulin, diacylglycerol kinase and peptidyl prolyl cis-trans isomerase in a secretagogue specific manner. To assess the role of calmodulin in human basophil histamine release, we triggered leukocytes with different secretagogues in the presence of putative inhibitors of calmodulin. Calcium ionophore-induced histamine release was reduced or blocked by calmidazolium, CGS 9343B, felodipine, metofenazate, and Ro 22-4839. H 186/86, a felodipine-related dihydropyridine derivative, blocked A23187-but not ionomycin-triggered histamine release, suggesting a difference in the mode of action of these ionophores. In contrast, leukocyte histamine release triggered by the purported protein kinase C (PKC) activator, 1,2-isopropylidene-3-decanoyl-sn-glycerol (IpOCOC9), was enhanced by calmidazolium, CGS 9349B and metofenazate but not affected by felodipine or Ro 22-4839, whereas the response triggered by 4 beta-phorbol 12-myristate 13-acetate (PMA) was reduced by metofenazate and Ro 22-4839 but not consistently affected by calmidazolium, CGS 9343B or felodipine. The PMA-induced histamine release was enhanced by H 186/86. Anti-IgE- and FMLP-induced responses were either unaffected or slightly enhanced by the examined calmodulin antagonists. In comparison with the calmodulin antagonists, R 59022, an inhibitor of diacylglycerol kinase, failed to reduce calcium ionophore-triggered histamine release, whereas FK506, an inhibitor of peptidyl prolyl cis-trans isomerase (PPI), reduced both anti-IgE- and ionophore-triggered responses. These results indicate that calmodulin constitutes an obligate link in signal transduction pathways leading to human leukocyte histamine release if the trigger is a calcium ionophore but not when responses are induced by anti-IgE, FMLP or PMA; a calmodulin-dependent component may rather balance responses induced by IpOCOC9.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280916", "title": "Cold urticaria as a model of mediator release: platelet factor 4, eosinophil cationic protein and histamine.", "content": "Platelet factor 4 (PF4) has previously been linked to precipitation of cold urticaria (CU). The aim of the study was to assess the liberation of PF4, eosinophil cationic protein (ECP) and histamine after cold challenge in patients with CU. Ten controls and 8 patients with CU verified by clinical data and cold challenge test were investigated. Assessment of histamine, ECP and PF4 were done using radioimmunoassays. In patients histamine increased after 10 min on the challenged arm (NS), PF4 increase was statistically significant (p less than 0.05) both in patients and controls. ECP release showed no significant changes. Treatment with doxepin results in clinical improvement, but no changes in mediator release were seen. Thus, in contrast to previous reports an increase of PF4 was seen both in controls as well as in patients. An involvement of ECP was not ascertained. Our data suggest that neither basophils, nor eosinophils or platelets are directly involved in cold urticaria and that mast cell-dependent mediators may be of greater relevance.", "contents": "Cold urticaria as a model of mediator release: platelet factor 4, eosinophil cationic protein and histamine. Platelet factor 4 (PF4) has previously been linked to precipitation of cold urticaria (CU). The aim of the study was to assess the liberation of PF4, eosinophil cationic protein (ECP) and histamine after cold challenge in patients with CU. Ten controls and 8 patients with CU verified by clinical data and cold challenge test were investigated. Assessment of histamine, ECP and PF4 were done using radioimmunoassays. In patients histamine increased after 10 min on the challenged arm (NS), PF4 increase was statistically significant (p less than 0.05) both in patients and controls. ECP release showed no significant changes. Treatment with doxepin results in clinical improvement, but no changes in mediator release were seen. Thus, in contrast to previous reports an increase of PF4 was seen both in controls as well as in patients. An involvement of ECP was not ascertained. Our data suggest that neither basophils, nor eosinophils or platelets are directly involved in cold urticaria and that mast cell-dependent mediators may be of greater relevance."} {"id": "PMID:1280917", "title": "Role of carbohydrate moieties in cross-reactivity between different components of Parietaria judaica pollen extract.", "content": "Cross-reactivity between the different components in Parietaria judaica pollen extract has been investigated by polyclonal as well as monoclonal antibodies before and after chemical deglycosylation obtained by trifluoromethanesulphonic acid (TFMS) treatment of the extract. In western blotting a polyclonal rabbit antiserum, obtained by injecting purified Par j I, was able to recognise many components of the native extract. However, its reactivity was restricted, after chemical deglycosylation of the extract, to the major allergen alone, indicating that its cross-reactivity was due to sugar moieties. Moreover, out of several monoclonal antibodies raised by injecting the whole Parietaria judaica extract, one (1A4/2F8) was also able in western blotting to recognise an epitope shared by many components of the extract except the major allergen Par j I. However, in this case the broad reactivity of the antibody was not affected by the deglycosylating procedure. When the reactivity of Parietaria judaica extract was tested before and after sugar removal, against specific IgE from a pool of patient sera, no differences could be demonstrated, thus indicating that carbohydrates are not strongly involved in the binding of Parietaria judaica-specific IgE. The results indicate that both proteic and carbohydratic cross-reactive epitopes are shared by many components of Parietaria judaica pollen extract.", "contents": "Role of carbohydrate moieties in cross-reactivity between different components of Parietaria judaica pollen extract. Cross-reactivity between the different components in Parietaria judaica pollen extract has been investigated by polyclonal as well as monoclonal antibodies before and after chemical deglycosylation obtained by trifluoromethanesulphonic acid (TFMS) treatment of the extract. In western blotting a polyclonal rabbit antiserum, obtained by injecting purified Par j I, was able to recognise many components of the native extract. However, its reactivity was restricted, after chemical deglycosylation of the extract, to the major allergen alone, indicating that its cross-reactivity was due to sugar moieties. Moreover, out of several monoclonal antibodies raised by injecting the whole Parietaria judaica extract, one (1A4/2F8) was also able in western blotting to recognise an epitope shared by many components of the extract except the major allergen Par j I. However, in this case the broad reactivity of the antibody was not affected by the deglycosylating procedure. When the reactivity of Parietaria judaica extract was tested before and after sugar removal, against specific IgE from a pool of patient sera, no differences could be demonstrated, thus indicating that carbohydrates are not strongly involved in the binding of Parietaria judaica-specific IgE. The results indicate that both proteic and carbohydratic cross-reactive epitopes are shared by many components of Parietaria judaica pollen extract."} {"id": "PMID:1280918", "title": "Use of [8-3H]guanine-labeled deoxyribonucleic acid to study alkylating agent reaction kinetics and stability.", "content": "Alkylation at the N7 position of guanine in DNA renders the C8-hydrogen acidic. This serves as the basis for an assay of guanine N7 alkylation using [8-3H]-guanine-labeled DNA. I modified the assay by preparing a high specific activity substrate in vitro and by replacing the distillation step with charcoal adsorption of substrate. Using the appearance of noncharcoal-adsorbable label as a measure of guanine-N7 alkylation I examined the reaction of DNA with dimethyl sulfate and mechlorethamine. The rate of reaction of dimethyl sulfate with the N7 position of guanine in DNA was constant over time, i.e., loss of label from DNA proceeded linearly with time. On the other hand, the rate of reaction of mechlorethamine with DNA increased with time, consistent with the initial formation of the reactive aziridinium ion. The assay can also be used to compare the reaction rates of various alkylating agents with DNA. Thus, the acridine mustards ICR-170 and quinacrine mustard were far more potent alkylating agents than mechlorethamine. Furthermore the assay may be used to determine the alkylating potency and stability of various alkylating agent preparations: while frozen solutions of acridine mustards in organic solvents retained alkylating activity for several months, different commercial preparations of quinacrine mustard had little or no alkylating activity.", "contents": "Use of [8-3H]guanine-labeled deoxyribonucleic acid to study alkylating agent reaction kinetics and stability. Alkylation at the N7 position of guanine in DNA renders the C8-hydrogen acidic. This serves as the basis for an assay of guanine N7 alkylation using [8-3H]-guanine-labeled DNA. I modified the assay by preparing a high specific activity substrate in vitro and by replacing the distillation step with charcoal adsorption of substrate. Using the appearance of noncharcoal-adsorbable label as a measure of guanine-N7 alkylation I examined the reaction of DNA with dimethyl sulfate and mechlorethamine. The rate of reaction of dimethyl sulfate with the N7 position of guanine in DNA was constant over time, i.e., loss of label from DNA proceeded linearly with time. On the other hand, the rate of reaction of mechlorethamine with DNA increased with time, consistent with the initial formation of the reactive aziridinium ion. The assay can also be used to compare the reaction rates of various alkylating agents with DNA. Thus, the acridine mustards ICR-170 and quinacrine mustard were far more potent alkylating agents than mechlorethamine. Furthermore the assay may be used to determine the alkylating potency and stability of various alkylating agent preparations: while frozen solutions of acridine mustards in organic solvents retained alkylating activity for several months, different commercial preparations of quinacrine mustard had little or no alkylating activity."} {"id": "PMID:1280919", "title": "The zymogram method for detection of ribonucleases after isoelectric focusing: analysis of multiple forms of human, bovine, and microbial enzymes.", "content": "A zymogram method for detection of in situ ribonuclease (RNase) activity, combined with isoelectric focusing in a thin layer of polyacrylamide gel (IEF-PAGE), has been developed. After incubation with a dried agarose film containing substrate RNA, ethidium bromide, and an appropriate reaction buffer, which was placed tightly on the top of the focused gel, sharp and distinct dark bands corresponding to RNase isoenzymes on a fluorescent background appeared under uv light. Addition of urea to the IEF-PAGE gel at a final concentration of 4.8 M permitted optimal focusing of the RNases. This method had not only a high sensitivity of less than 0.1 ng purified RNase A, but also a high band resolution compared with the immunostaining method. It was also useful for analysis of purified enzymes, including bovine pancreatic RNases and two types of human urine RNase as mammalian enzymes, and RNases T1 and T2 as microbial enzymes, as well as for detection of RNases present in crude tissue extracts, resulting in more detailed elucidation of the multiplicity of these enzymes.", "contents": "The zymogram method for detection of ribonucleases after isoelectric focusing: analysis of multiple forms of human, bovine, and microbial enzymes. A zymogram method for detection of in situ ribonuclease (RNase) activity, combined with isoelectric focusing in a thin layer of polyacrylamide gel (IEF-PAGE), has been developed. After incubation with a dried agarose film containing substrate RNA, ethidium bromide, and an appropriate reaction buffer, which was placed tightly on the top of the focused gel, sharp and distinct dark bands corresponding to RNase isoenzymes on a fluorescent background appeared under uv light. Addition of urea to the IEF-PAGE gel at a final concentration of 4.8 M permitted optimal focusing of the RNases. This method had not only a high sensitivity of less than 0.1 ng purified RNase A, but also a high band resolution compared with the immunostaining method. It was also useful for analysis of purified enzymes, including bovine pancreatic RNases and two types of human urine RNase as mammalian enzymes, and RNases T1 and T2 as microbial enzymes, as well as for detection of RNases present in crude tissue extracts, resulting in more detailed elucidation of the multiplicity of these enzymes."} {"id": "PMID:1280920", "title": "Analysis of glycoform of O-glycan from human myeloma immunoglobulin A1 by gas-phase hydrazinolysis following pyridylamination of oligosaccharides.", "content": "A comparative study was made on the glycoform of O-glycan from human myeloma immunoglobulin A1. By gas-phase hydrazinolysis, O-glycan was released from its hinge portion. The released oligosaccharide was pyridylaminated and separated by a two-dimensional analytical method of gel filtration and reverse-phase HPLC. Four major pyridylamino derivatives (P1-P4) were obtained. The neutral component (P4) among them was identified as Gal beta 1,3GalNAc-PA by cochromatography with an authentic standard pyridylamino sugar. The desialylation of the other components indicated the largest P1 and middle size P2 components possibly corresponded to a disialylated structure, NeuAc alpha 2,3Gal beta 1,3(NeuAc alpha 2,6)GalNAc-PA, and a monosialylated component, NeuAc alpha 2,3Gal beta 1,3GalNAc-PA, respectively. The structural assignment of P3 is still incomplete. Four similar components were also detected in bovine fetuin whose relative content (P1:P2: P3:P:4) was 16:43:19:22. The relative content (%) of P1-P4 (glycoform) in IgA1 from the healthy control was 10.1 +/- 3.3, 48.2 +/- 4.6, 7.0 +/- 2.6, and 34.7 +/- 4.5. The glycoform of O-glycan on IgA1 thus appears the same for any individual. Analysis of IgA1 myeloma protein indicated glycoforms distinct from those of the healthy controls. The relative content of these component could be classed as 2:8:0:90 (Type I, only one case designated as Kita), 5:24:3:68 (Type II, seven cases), and 9:41:5:45 (Type III, four cases). Thus, the results for IgA1 myeloma protein indicate that at least three glycoforms of O-glycan are possible for the IgA1 hinge structure. However, only one glycoform was found in the healthy controls.", "contents": "Analysis of glycoform of O-glycan from human myeloma immunoglobulin A1 by gas-phase hydrazinolysis following pyridylamination of oligosaccharides. A comparative study was made on the glycoform of O-glycan from human myeloma immunoglobulin A1. By gas-phase hydrazinolysis, O-glycan was released from its hinge portion. The released oligosaccharide was pyridylaminated and separated by a two-dimensional analytical method of gel filtration and reverse-phase HPLC. Four major pyridylamino derivatives (P1-P4) were obtained. The neutral component (P4) among them was identified as Gal beta 1,3GalNAc-PA by cochromatography with an authentic standard pyridylamino sugar. The desialylation of the other components indicated the largest P1 and middle size P2 components possibly corresponded to a disialylated structure, NeuAc alpha 2,3Gal beta 1,3(NeuAc alpha 2,6)GalNAc-PA, and a monosialylated component, NeuAc alpha 2,3Gal beta 1,3GalNAc-PA, respectively. The structural assignment of P3 is still incomplete. Four similar components were also detected in bovine fetuin whose relative content (P1:P2: P3:P:4) was 16:43:19:22. The relative content (%) of P1-P4 (glycoform) in IgA1 from the healthy control was 10.1 +/- 3.3, 48.2 +/- 4.6, 7.0 +/- 2.6, and 34.7 +/- 4.5. The glycoform of O-glycan on IgA1 thus appears the same for any individual. Analysis of IgA1 myeloma protein indicated glycoforms distinct from those of the healthy controls. The relative content of these component could be classed as 2:8:0:90 (Type I, only one case designated as Kita), 5:24:3:68 (Type II, seven cases), and 9:41:5:45 (Type III, four cases). Thus, the results for IgA1 myeloma protein indicate that at least three glycoforms of O-glycan are possible for the IgA1 hinge structure. However, only one glycoform was found in the healthy controls."} {"id": "PMID:1280921", "title": "Activity staining of endoglucanases in polyacrylamide gels.", "content": "The endoglucanases of Penicillium funiculosum were analyzed for the presence of multiple forms using a modified version of the Congo red method. Postelectrophoretic slab gels were directly incubated in a solution of carboxymethylcellulose for a period as short as 15 min and then the activities were visualized by staining with Congo red. Ten distinct bands of clearances were obtained indicating the presence of at least as many multiple forms.", "contents": "Activity staining of endoglucanases in polyacrylamide gels. The endoglucanases of Penicillium funiculosum were analyzed for the presence of multiple forms using a modified version of the Congo red method. Postelectrophoretic slab gels were directly incubated in a solution of carboxymethylcellulose for a period as short as 15 min and then the activities were visualized by staining with Congo red. Ten distinct bands of clearances were obtained indicating the presence of at least as many multiple forms."} {"id": "PMID:1280922", "title": "An extracellular matrix infrastructure provides support for murine secondary palatal shelf remodelling.", "content": "A crucial part of secondary palate morphogenesis is the movement of the palatal shelves from an initial vertical position on either side of the tongue to a final horizontal one above it to achieve palate closure. The immunocytochemical localization of extracellular matrix (ECM) molecules in the palatal shelf during this remodelling and reorientation revealed the existence of an ECM infrastructure within the mesenchyme. The major components of this infrastructure were collagen III, fibronectin, and hyaluronate (HA). With remodelling, HA's domain within the mesenchyme was expanded, whereas those of fibronectin and collagen III became more circumscribed. The expansion of an HA-rich matrix within the mesenchyme is thought to be crucial for palatal reorientation. The results of this study suggest that, as this expansion occurs, it is modulated by collagen and fibronectin components of the ECM infrastructure. Prior to shelf remodelling, this infrastructure may be anchored by a specialized region of the midoral epithelial-mesenchymal interface and the subjacent mesenchyme which is characterized by the unique distribution of collagen III, fibronectin, and tenascin. The midoral palatal epithelium also may play a role in directing shelf expansion. This epithelial region undergoes changes in cell packing and epithelial cell layering that correlate with shelf remodelling. These changes occur concomitantly with changes in the expression of collagen III, collagen IV, and laminin within the underlying basement membrane. The localization and patterning of tenascin within the developing palate suggests that it not only contributes to the postulated anchoring structure of the midoral epithelial-mesenchymal region, but also plays a role in the determining the fate of the medial edge epithelial cells during the final stage of palate closure.", "contents": "An extracellular matrix infrastructure provides support for murine secondary palatal shelf remodelling. A crucial part of secondary palate morphogenesis is the movement of the palatal shelves from an initial vertical position on either side of the tongue to a final horizontal one above it to achieve palate closure. The immunocytochemical localization of extracellular matrix (ECM) molecules in the palatal shelf during this remodelling and reorientation revealed the existence of an ECM infrastructure within the mesenchyme. The major components of this infrastructure were collagen III, fibronectin, and hyaluronate (HA). With remodelling, HA's domain within the mesenchyme was expanded, whereas those of fibronectin and collagen III became more circumscribed. The expansion of an HA-rich matrix within the mesenchyme is thought to be crucial for palatal reorientation. The results of this study suggest that, as this expansion occurs, it is modulated by collagen and fibronectin components of the ECM infrastructure. Prior to shelf remodelling, this infrastructure may be anchored by a specialized region of the midoral epithelial-mesenchymal interface and the subjacent mesenchyme which is characterized by the unique distribution of collagen III, fibronectin, and tenascin. The midoral palatal epithelium also may play a role in directing shelf expansion. This epithelial region undergoes changes in cell packing and epithelial cell layering that correlate with shelf remodelling. These changes occur concomitantly with changes in the expression of collagen III, collagen IV, and laminin within the underlying basement membrane. The localization and patterning of tenascin within the developing palate suggests that it not only contributes to the postulated anchoring structure of the midoral epithelial-mesenchymal region, but also plays a role in the determining the fate of the medial edge epithelial cells during the final stage of palate closure."} {"id": "PMID:1280923", "title": "Expression of intermediate filaments and actins in human dental pulp and embryonic dental papilla.", "content": "The localization of different cytoskeletal proteins (keratin, vimentin, desmin, actin, and alpha-smooth muscle actin) was examined by immunohistochemistry in normal human adult dental pulp and compared with dental papilla of tooth germs. Keratin and actin were localized in enamel organ. Vimentin and actin were observed in the dental papilla and in the adult dental pulp. Desmin and alpha-smooth muscle actin were present only in the vessel walls. These data are discussed paying particular attention to the origin and the peculiar functional characters of the dental papilla and pulp.", "contents": "Expression of intermediate filaments and actins in human dental pulp and embryonic dental papilla. The localization of different cytoskeletal proteins (keratin, vimentin, desmin, actin, and alpha-smooth muscle actin) was examined by immunohistochemistry in normal human adult dental pulp and compared with dental papilla of tooth germs. Keratin and actin were localized in enamel organ. Vimentin and actin were observed in the dental papilla and in the adult dental pulp. Desmin and alpha-smooth muscle actin were present only in the vessel walls. These data are discussed paying particular attention to the origin and the peculiar functional characters of the dental papilla and pulp."} {"id": "PMID:1280925", "title": "Single-step technique for staining Anaplasma marginale in bovine blood smears.", "content": "Three available differential stains, Camco-Quik, Diff-Quik, and Wright-Giesma were compared for detection of intraerythrocytic Anaplasma marginale in bovine blood smears. In samples where < 1% to more than 51% of the RBC were infected, statistical analysis of the data indicated no significant difference in the detection of A marginale with Camco-Quik or Diff-Quik stains. However, a significantly lower percentage of infected RBC were detected when blood smears were stained with the Wright-Giemsa stain, compared with the other 2 methods.", "contents": "Single-step technique for staining Anaplasma marginale in bovine blood smears. Three available differential stains, Camco-Quik, Diff-Quik, and Wright-Giesma were compared for detection of intraerythrocytic Anaplasma marginale in bovine blood smears. In samples where < 1% to more than 51% of the RBC were infected, statistical analysis of the data indicated no significant difference in the detection of A marginale with Camco-Quik or Diff-Quik stains. However, a significantly lower percentage of infected RBC were detected when blood smears were stained with the Wright-Giemsa stain, compared with the other 2 methods."} {"id": "PMID:1280926", "title": "Use of a biological extract of Serratia marcescens to decrease doxorubicin-induced myelosuppression in dogs.", "content": "Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered SC to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Use of a biological extract of Serratia marcescens to decrease doxorubicin-induced myelosuppression in dogs. Fifteen dogs were given doxorubicin, IV, at a dosage of 30 mg/m2 of body surface. A commercially available biological extract of Serratia marcescens (BESM) was administered SC to 9 of these dogs (0.04 mg/kg of body weight every third day, n = 2; 0.08 mg/kg every other day, n = 2; and 0.08 mg/kg daily, n = 5), beginning the day after administration of doxorubicin, in an attempt to find an optimal dosage and schedule of administration of BESM to reduce the duration and severity of chemotherapy-induced myelosuppression. Nine additional dogs were randomized into 3 groups of 3 dogs to receive 1 of the following dosages of BESM SC: 0.08, 0.16, and 0.32 mg/kg. Serum was harvested immediately prior to treatment and at 2, 4, 6, 8, 12, 24, 48, and 72 hours from this latter group of dogs for subsequent analysis of canine granulocyte colony-stimulating factor (G-CSF) by enzyme immunoassay. Increasing the dosage and schedule of administration of BESM reduced the duration and severity of doxorubicin-induced myelosuppression. Neutrophil counts of the group of dogs given BESM daily at a dosage of 0.08 mg/kg and the controls were evaluated statistically. The neutrophil count increased significantly (P < 0.05) above pretreatment values in BESM-treated dogs after day 7. Median neutrophil counts of the BESM-treated dogs were never significantly lower than pretreatment values, whereas the median counts of the dogs treated with doxorubicin alone were significantly below normal for 6 days (days 7-12).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280927", "title": "Keratin and associated proteins of the equine hoof wall.", "content": "In this study, we described water-insoluble proteins extracted from the germinative regions (stratum internum and coronary band epithelium) and the cornified outer surface (stratum medium) of the equine hoof wall. Two major types of polypeptides were identified: the intermediate filaments (IF) and the IF-associated proteins. The IF, including keratins, composed a major portion of this fraction, had electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the range of 40 to 80 kDa, and reacted with acidic or basic keratin-specific monoclonal antibodies. Differences in the composition of keratins between germinative layers and the stratum medium were seen. Another less well-characterized group of polypeptides associated with the IF also were extracted with the water-insoluble polypeptide fraction. These associated proteins had an apparent molecular weight between 10 and 30 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and contained a higher percentage of sulfur-containing amino acids than did the IF. Water-insoluble protein fractions compared favorably with those found in other less-specialized keratinizing tissue with respect to size, immunoreactivity with monoclonal antibody, and amino acid composition.", "contents": "Keratin and associated proteins of the equine hoof wall. In this study, we described water-insoluble proteins extracted from the germinative regions (stratum internum and coronary band epithelium) and the cornified outer surface (stratum medium) of the equine hoof wall. Two major types of polypeptides were identified: the intermediate filaments (IF) and the IF-associated proteins. The IF, including keratins, composed a major portion of this fraction, had electrophoretic mobilities on sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the range of 40 to 80 kDa, and reacted with acidic or basic keratin-specific monoclonal antibodies. Differences in the composition of keratins between germinative layers and the stratum medium were seen. Another less well-characterized group of polypeptides associated with the IF also were extracted with the water-insoluble polypeptide fraction. These associated proteins had an apparent molecular weight between 10 and 30 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and contained a higher percentage of sulfur-containing amino acids than did the IF. Water-insoluble protein fractions compared favorably with those found in other less-specialized keratinizing tissue with respect to size, immunoreactivity with monoclonal antibody, and amino acid composition."} {"id": "PMID:1280928", "title": "Mucus hypersecretion in bronchiectasis. The role of neutrophil proteases.", "content": "To investigate the role of neutrophil proteases in the pathogenesis of mucus hypersecretion in bronchiectasis, we collected sputum samples from seven patients with bronchiectasis and measured their secretagogue activity by examining secretion of radiolabeled macromolecules by bovine airway submucosal gland cells incubated with sputum supernatants. There was marked secretagogue activity in bronchiectasis sputum, reaching a maximum of 1,963 +/- 292% (mean +/- SEM) above baseline at 1:15 dilution. Addition of ICI 200,355 (10(-5) M), a selective human neutrophil elastase inhibitor, decreased the secretory response markedly (72.53 +/- 5.89% reduction). The combination of aprotinin, an inhibitor of cathepsin G, and ICI 200,355 caused significantly more reduction in the secretory response than ICI 200,355 alone (89.12 +/- 3.8 versus 72.53 +/- 5.89% reduction, p < 0.05). We conclude that bronchiectasis sputum causes a large secretory response from tracheal submucosal glands due mostly to neutrophil proteases.", "contents": "Mucus hypersecretion in bronchiectasis. The role of neutrophil proteases. To investigate the role of neutrophil proteases in the pathogenesis of mucus hypersecretion in bronchiectasis, we collected sputum samples from seven patients with bronchiectasis and measured their secretagogue activity by examining secretion of radiolabeled macromolecules by bovine airway submucosal gland cells incubated with sputum supernatants. There was marked secretagogue activity in bronchiectasis sputum, reaching a maximum of 1,963 +/- 292% (mean +/- SEM) above baseline at 1:15 dilution. Addition of ICI 200,355 (10(-5) M), a selective human neutrophil elastase inhibitor, decreased the secretory response markedly (72.53 +/- 5.89% reduction). The combination of aprotinin, an inhibitor of cathepsin G, and ICI 200,355 caused significantly more reduction in the secretory response than ICI 200,355 alone (89.12 +/- 3.8 versus 72.53 +/- 5.89% reduction, p < 0.05). We conclude that bronchiectasis sputum causes a large secretory response from tracheal submucosal glands due mostly to neutrophil proteases."} {"id": "PMID:1280929", "title": "Detection of dysplasia and carcinoma in situ by ratio fluorometry.", "content": "Fluorescence bronchoscopy was performed in 82 volunteers recruited from occupational groups at risk of exposure to asbestos and/or diesel fumes to determine whether differences in tissue autofluorescence between normal and malignant bronchial tissues can be used to improve the sensitivity of standard fiberoptic bronchoscopy in detecting dysplasic and carcinoma in situ (CIS). This study consisted of 25 nonsmokers, 40 exsmokers, and 17 current smokers with mean ages of 52, 55, and 49 yr, respectively. Tissue autofluorescence was induced by a blue light from an He-Cd laser coupled to the illumination channel of the bronchoscope and analyzed by a ratiofluorometer. One or more sites of moderate or severe dysplasia were found in 12% of the exsmokers and current smokers but in none of the nonsmoker volunteers. CIS was found in two of the exsmokers. The sensitivity of fluorescence bronchoscopy (86%) was found to be 50% better than that of conventional white-light bronchoscopy (52%) in detecting dysplasia and CIS. Pre- and post-bronchoscopy sputum cytology failed to detect these precancerous lesions. Our results suggest that fluorescence bronchoscopy may be an important new method that can improve the ability to detect and localize precancerous and/or CIS lesions.", "contents": "Detection of dysplasia and carcinoma in situ by ratio fluorometry. Fluorescence bronchoscopy was performed in 82 volunteers recruited from occupational groups at risk of exposure to asbestos and/or diesel fumes to determine whether differences in tissue autofluorescence between normal and malignant bronchial tissues can be used to improve the sensitivity of standard fiberoptic bronchoscopy in detecting dysplasic and carcinoma in situ (CIS). This study consisted of 25 nonsmokers, 40 exsmokers, and 17 current smokers with mean ages of 52, 55, and 49 yr, respectively. Tissue autofluorescence was induced by a blue light from an He-Cd laser coupled to the illumination channel of the bronchoscope and analyzed by a ratiofluorometer. One or more sites of moderate or severe dysplasia were found in 12% of the exsmokers and current smokers but in none of the nonsmoker volunteers. CIS was found in two of the exsmokers. The sensitivity of fluorescence bronchoscopy (86%) was found to be 50% better than that of conventional white-light bronchoscopy (52%) in detecting dysplasia and CIS. Pre- and post-bronchoscopy sputum cytology failed to detect these precancerous lesions. Our results suggest that fluorescence bronchoscopy may be an important new method that can improve the ability to detect and localize precancerous and/or CIS lesions."} {"id": "PMID:1280933", "title": "Effect of inflammation of enteric nerves. Cytokine-induced changes in neurotransmitter content and release.", "content": "The results of our previously published work provide evidence of inflammation-induced functional disturbances in the enteric nervous system. Data presented in this paper describe our preliminary results indicating that the altered function in enteric nerves in the nematode-infected rat model of intestinal inflammation is mediated by interleukin-1. This is based on the ability of the exogenous cytokine to mimic changes observed in the model, and on the ability of a specific IL-1 antagonist to attenuate these changes. In addition, we have identified mechanisms underlying the actions of IL-1 in the myenteric plexus. Our data are consistent with a direct interaction between the cytokine and neural membranes. In addition, the delayed effect of IL-1 beta on neurotransmitter release appears to be due to the release of endogenous IL-1, most likely from macrophage-like cells in the myenteric plexus (Fig. 3). If such cells possess receptors for neuropeptides, as has been found with macrophages elsewhere in the gut, a neuroimmune axis would exist in the myenteric plexus. Thus, the finding of a source of IL-1 in the plexus of the noninflamed intestine invites speculation on a neuromodulatory role of the cytokine within the enteric nervous system.", "contents": "Effect of inflammation of enteric nerves. Cytokine-induced changes in neurotransmitter content and release. The results of our previously published work provide evidence of inflammation-induced functional disturbances in the enteric nervous system. Data presented in this paper describe our preliminary results indicating that the altered function in enteric nerves in the nematode-infected rat model of intestinal inflammation is mediated by interleukin-1. This is based on the ability of the exogenous cytokine to mimic changes observed in the model, and on the ability of a specific IL-1 antagonist to attenuate these changes. In addition, we have identified mechanisms underlying the actions of IL-1 in the myenteric plexus. Our data are consistent with a direct interaction between the cytokine and neural membranes. In addition, the delayed effect of IL-1 beta on neurotransmitter release appears to be due to the release of endogenous IL-1, most likely from macrophage-like cells in the myenteric plexus (Fig. 3). If such cells possess receptors for neuropeptides, as has been found with macrophages elsewhere in the gut, a neuroimmune axis would exist in the myenteric plexus. Thus, the finding of a source of IL-1 in the plexus of the noninflamed intestine invites speculation on a neuromodulatory role of the cytokine within the enteric nervous system."} {"id": "PMID:1280935", "title": "Analyzing mast cell development and function using mice carrying mutations at W/c-kit or Sl/MGF (SCF) loci.", "content": "Mast cells have been implicated in a wide variety of biological responses, but identifying the nature and importance of the mast cell's specific contributions to these reactions has been difficult. W/Wv mice have mutations affecting the c-kit tyrosine kinase receptor which is encoded at the W locus and which is necessary for normal mast cell development. In W/Wv mice, the cells which ordinarily give rise to normal mast cell populations do not adequately respond to a major migration, survival, proliferation and maturation factor expressed in the microenvironments where mast cells ordinarily develop: the c-kit receptor ligand, SCF. As a result, W/Wv mice virtually lack tissue mast cells. However, adoptive transfer to W/Wv mice of immature mast cells derived in vitro from the bone marrow cells of the congenic normal (+/+) mice selectively repairs the mast cell deficiency of the W/Wv recipients. These \"mast cell knock-in\" mice can be used to analyze the expression of biological responses in tissues which differ only because they do or do not contain populations of mast cells. This approach permits identification and quantification of the specific contributions of the mast cell to biological responses expressed in the skin, gastrointestinal tract and other anatomical sites, and also greatly facilitates analysis of the mechanisms by which mast cells influence these responses.", "contents": "Analyzing mast cell development and function using mice carrying mutations at W/c-kit or Sl/MGF (SCF) loci. Mast cells have been implicated in a wide variety of biological responses, but identifying the nature and importance of the mast cell's specific contributions to these reactions has been difficult. W/Wv mice have mutations affecting the c-kit tyrosine kinase receptor which is encoded at the W locus and which is necessary for normal mast cell development. In W/Wv mice, the cells which ordinarily give rise to normal mast cell populations do not adequately respond to a major migration, survival, proliferation and maturation factor expressed in the microenvironments where mast cells ordinarily develop: the c-kit receptor ligand, SCF. As a result, W/Wv mice virtually lack tissue mast cells. However, adoptive transfer to W/Wv mice of immature mast cells derived in vitro from the bone marrow cells of the congenic normal (+/+) mice selectively repairs the mast cell deficiency of the W/Wv recipients. These \"mast cell knock-in\" mice can be used to analyze the expression of biological responses in tissues which differ only because they do or do not contain populations of mast cells. This approach permits identification and quantification of the specific contributions of the mast cell to biological responses expressed in the skin, gastrointestinal tract and other anatomical sites, and also greatly facilitates analysis of the mechanisms by which mast cells influence these responses."} {"id": "PMID:1280937", "title": "The cortical lesion of Huntington's disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex.", "content": "Huntington's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma-aminobutyric acid (GABA)-ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N-methyl-D-aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA-induced lesions showed striking sparing of parvalbumin-positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA-induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease.", "contents": "The cortical lesion of Huntington's disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex. Huntington's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma-aminobutyric acid (GABA)-ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N-methyl-D-aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA-induced lesions showed striking sparing of parvalbumin-positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA-induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease."} {"id": "PMID:1280938", "title": "[Combined experimental use of vaccine against acute human encephalomyelitis and immunomodulators].", "content": "Combined use of vaccine and immunomodulators such as ridostin, inosiplex and polyribonate against acute encephalomyelitis of humans (AEMHs) was studied. It was shown that low immunogenic doses of the vaccine did not provide a protective action against the virus of AEMHs while after administration of the vaccine in combination with the immunomodulators there was protection in all the groups of the animals exposed to the low immunogenic doses of the vaccine during the first immunization. It was noted in regard to all the combinations of the immunomodulators and vaccine used in the low immunogenic doses that the level of the increase in the titer of the virus-specific antibodies, the proliferative activity to the specific antigen and mitogens and of interferon induction depended on the immunomodulator type. At the same time, it was found that the marked production of interferon within the first 24 hours observed after the use of the combination of inosiplex, ridostin and the vaccine resulted in increased activity of natural killer cells and lower proliferative activity of cells and production of virus-specific antibodies. This was indicative of the necessity of choosing the immunomodulators, their doses and time of the administration in relation to the immunization.", "contents": "[Combined experimental use of vaccine against acute human encephalomyelitis and immunomodulators]. Combined use of vaccine and immunomodulators such as ridostin, inosiplex and polyribonate against acute encephalomyelitis of humans (AEMHs) was studied. It was shown that low immunogenic doses of the vaccine did not provide a protective action against the virus of AEMHs while after administration of the vaccine in combination with the immunomodulators there was protection in all the groups of the animals exposed to the low immunogenic doses of the vaccine during the first immunization. It was noted in regard to all the combinations of the immunomodulators and vaccine used in the low immunogenic doses that the level of the increase in the titer of the virus-specific antibodies, the proliferative activity to the specific antigen and mitogens and of interferon induction depended on the immunomodulator type. At the same time, it was found that the marked production of interferon within the first 24 hours observed after the use of the combination of inosiplex, ridostin and the vaccine resulted in increased activity of natural killer cells and lower proliferative activity of cells and production of virus-specific antibodies. This was indicative of the necessity of choosing the immunomodulators, their doses and time of the administration in relation to the immunization."} {"id": "PMID:1280939", "title": "[Chemical modification of an antineoplastic antibiotic bleomycetin by the C-end fragment].", "content": "Bleomycetin, an antitumor antibiotic, was subjected to chemical modification by the C-end fragment i.e. the residue of 3-[(4-aminobutyl)amino]propylamine (spermidine++) with acylation, carbamoylation and reducing alkylation, which yielded its new semisynthetic derivatives. The use of physicochemical methods showed that the chemical modification involved the primary and secondary amino groups++ of spermidine++ and gave rise to N,N'-diacyl, N,N'-dicarbamoyl and N,N'-dialkyl bleomycetins. The biological properties of the derivatives, i.e. their cytotoxic activity, acute and pulmonary toxicities were studied. The transformation of bleomycetin by the C-end fragment lowered the antibiotic toxicity and was believed to be a promising approach to modifying its molecule.", "contents": "[Chemical modification of an antineoplastic antibiotic bleomycetin by the C-end fragment]. Bleomycetin, an antitumor antibiotic, was subjected to chemical modification by the C-end fragment i.e. the residue of 3-[(4-aminobutyl)amino]propylamine (spermidine++) with acylation, carbamoylation and reducing alkylation, which yielded its new semisynthetic derivatives. The use of physicochemical methods showed that the chemical modification involved the primary and secondary amino groups++ of spermidine++ and gave rise to N,N'-diacyl, N,N'-dicarbamoyl and N,N'-dialkyl bleomycetins. The biological properties of the derivatives, i.e. their cytotoxic activity, acute and pulmonary toxicities were studied. The transformation of bleomycetin by the C-end fragment lowered the antibiotic toxicity and was believed to be a promising approach to modifying its molecule."} {"id": "PMID:1280936", "title": "Different distributions of lung and blood lymphocyte subsets in pediatric AIDS or tuberculosis.", "content": "Pulmonary immunity has not been studied in children with acquired immunodeficiency syndrome (AIDS) or tuberculosis (TB), even though lungs of both children and adults infected with human immunodeficiency virus (HIV-1) or Mycobacterium tuberculosis are affected frequently and severely. In the present studies, the distributions of T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in bronchoalveolar lavage fluid (BALF) and blood of children with AIDS (N = 28) and children with pulmonary TB (N = 18) were determined using direct immunofluorescence (flow microfluorimetry). The distributions of lymphocyte subsets in BALF differed dramatically from those in blood. In pediatric AIDS, reduction of CD4/CD8 ratio was much more pronounced in BALF than in peripheral blood (0.15 +/- 0.04 vs. 0.43 +/- 0.11). This difference was due to selective depletion of BALF CD4+ lymphocytes, rather than to a great influx of CD8+ cells into the lung. In childhood TB, the CD4/CD8 ratio in BALF also was significantly decreased, despite its elevation in blood (1.02 +/- 0.26 vs. 1.96 +/- 0.32). The results show that (1) examination of peripheral blood lymphocytes does not reflect the kind and extent of changes observed in the distribution of pulmonary lymphocyte subsets, and (2) the profound decrease of the CD4/CD8 ratios in BALF of children with AIDS or TB is due to decreased percentages and absolute numbers of BALF CD4+ lymphocytes. The data suggest that analysis of BALF provides a more accurate evaluation of the patient pulmonary immune status than monitoring peripheral blood.", "contents": "Different distributions of lung and blood lymphocyte subsets in pediatric AIDS or tuberculosis. Pulmonary immunity has not been studied in children with acquired immunodeficiency syndrome (AIDS) or tuberculosis (TB), even though lungs of both children and adults infected with human immunodeficiency virus (HIV-1) or Mycobacterium tuberculosis are affected frequently and severely. In the present studies, the distributions of T (CD3+, CD4+, CD8+) and B (CD19+) lymphocytes in bronchoalveolar lavage fluid (BALF) and blood of children with AIDS (N = 28) and children with pulmonary TB (N = 18) were determined using direct immunofluorescence (flow microfluorimetry). The distributions of lymphocyte subsets in BALF differed dramatically from those in blood. In pediatric AIDS, reduction of CD4/CD8 ratio was much more pronounced in BALF than in peripheral blood (0.15 +/- 0.04 vs. 0.43 +/- 0.11). This difference was due to selective depletion of BALF CD4+ lymphocytes, rather than to a great influx of CD8+ cells into the lung. In childhood TB, the CD4/CD8 ratio in BALF also was significantly decreased, despite its elevation in blood (1.02 +/- 0.26 vs. 1.96 +/- 0.32). The results show that (1) examination of peripheral blood lymphocytes does not reflect the kind and extent of changes observed in the distribution of pulmonary lymphocyte subsets, and (2) the profound decrease of the CD4/CD8 ratios in BALF of children with AIDS or TB is due to decreased percentages and absolute numbers of BALF CD4+ lymphocytes. The data suggest that analysis of BALF provides a more accurate evaluation of the patient pulmonary immune status than monitoring peripheral blood."} {"id": "PMID:1280941", "title": "Identification of epitopes associated with different biological activities on the glycoprotein of vesicular stomatitis virus by use of monoclonal antibodies.", "content": "Thirteen monoclonal antibodies (MAbs) to the glycoprotein (G) of vesicular stomatitis virus (VSV) serotype Indiana were prepared and examined for their effects on various biological activities of VSV, including in vitro infection, hemagglutination, adsorption to cells, and mediation of cell fusion. Competitive binding assays with these MAbs revealed the presence of at least seven distinct antigenic determinants (epitopes) on the G protein. In some cases, overlappings among epitopes to various degrees were observed as partial inhibition or binding enhancement. The MAbs to all the epitopes but one (epitopes 1-6) reacted with the denatured G protein in a Western immunoblot analysis. Four of the epitopes (epitopes 2, 4, 5, and 7) were involved in neutralization and two (epitopes 1 and 2) in hemagglutination inhibition. None of the MAbs inhibited the adsorption of radiolabeled VSV to BHK-21 cells; the MAbs to epitope 2 slightly enhanced the virus adsorption. All neutralization epitopes except epitope 2 (epitopes 4, 5, and 7) were associated with inhibition of VSV-mediated cell fusion. These results show a direct spatial relationship between the epitopes recognized by the MAbs and functional sites on G protein and further insights into the structure and function of G protein.", "contents": "Identification of epitopes associated with different biological activities on the glycoprotein of vesicular stomatitis virus by use of monoclonal antibodies. Thirteen monoclonal antibodies (MAbs) to the glycoprotein (G) of vesicular stomatitis virus (VSV) serotype Indiana were prepared and examined for their effects on various biological activities of VSV, including in vitro infection, hemagglutination, adsorption to cells, and mediation of cell fusion. Competitive binding assays with these MAbs revealed the presence of at least seven distinct antigenic determinants (epitopes) on the G protein. In some cases, overlappings among epitopes to various degrees were observed as partial inhibition or binding enhancement. The MAbs to all the epitopes but one (epitopes 1-6) reacted with the denatured G protein in a Western immunoblot analysis. Four of the epitopes (epitopes 2, 4, 5, and 7) were involved in neutralization and two (epitopes 1 and 2) in hemagglutination inhibition. None of the MAbs inhibited the adsorption of radiolabeled VSV to BHK-21 cells; the MAbs to epitope 2 slightly enhanced the virus adsorption. All neutralization epitopes except epitope 2 (epitopes 4, 5, and 7) were associated with inhibition of VSV-mediated cell fusion. These results show a direct spatial relationship between the epitopes recognized by the MAbs and functional sites on G protein and further insights into the structure and function of G protein."} {"id": "PMID:1280942", "title": "Production, characterization and use of monoclonal antibodies to grapevine virus A.", "content": "Four stable hybridoma cell lines secreting monoclonal antibodies to grapevine closterovirus A (GVA) were obtained by fusing spleen cells of immunized BALB/c mice with mouse myeloma cell line Sp2/0-Ag 14. In ELISA all MAbs reacted with virus in leaf extracts from Nicotiana benthamiana, glass-house-, field-, or in vitro-grown grapevines, or with cortical shavings from mature grape canes. In IEM tests, only one of the MAbs (PA3.F5) decorated virus particles on the entire surface. This MAb was likely induced by a surface antigenic determinant, whereas the other three MAbs (PA3.D 11, PA3.C 6, and PA3.B 9) were originated by cryptotopes. Coupling polyclonal antibodies for coating protein A-sensitized plates, and monoclonal antibody conjugates for antigen detection, gave highly efficient and reproducible results for identification of GVA in field-grown grapevines.", "contents": "Production, characterization and use of monoclonal antibodies to grapevine virus A. Four stable hybridoma cell lines secreting monoclonal antibodies to grapevine closterovirus A (GVA) were obtained by fusing spleen cells of immunized BALB/c mice with mouse myeloma cell line Sp2/0-Ag 14. In ELISA all MAbs reacted with virus in leaf extracts from Nicotiana benthamiana, glass-house-, field-, or in vitro-grown grapevines, or with cortical shavings from mature grape canes. In IEM tests, only one of the MAbs (PA3.F5) decorated virus particles on the entire surface. This MAb was likely induced by a surface antigenic determinant, whereas the other three MAbs (PA3.D 11, PA3.C 6, and PA3.B 9) were originated by cryptotopes. Coupling polyclonal antibodies for coating protein A-sensitized plates, and monoclonal antibody conjugates for antigen detection, gave highly efficient and reproducible results for identification of GVA in field-grown grapevines."} {"id": "PMID:1280940", "title": "Decondensation of human sperm nuclei and HP1 protamine degradation from normospermia and asthenospermia in Xenopus egg extracts.", "content": "The process of human sperm decondensation has been studied in vitro in cytoplasmic extracts prepared from unfertilized Xenopus laevis eggs. The chromatin decondensation-recondensation cycle was divided into four stages according to chromatin appearance. Spermatozoa from normospermia and asthenospermia were evaluated according to their capacity to reach these stages, and their DNA integrity was assessed by acridine orange (AO) staining. We observed a significant difference between normospermia and asthenozoospermia in the ability to achieve the cycle of chromatin decondensation-recondensation. These results correlated with AO staining. The role of human protamine 1 degradation in the decondensation process was evaluated by immunostaining. It was found not to be a prerequisite for the earlier stage of chromatin decondensation and it was not implied in the latest stages of pronuclear development.", "contents": "Decondensation of human sperm nuclei and HP1 protamine degradation from normospermia and asthenospermia in Xenopus egg extracts. The process of human sperm decondensation has been studied in vitro in cytoplasmic extracts prepared from unfertilized Xenopus laevis eggs. The chromatin decondensation-recondensation cycle was divided into four stages according to chromatin appearance. Spermatozoa from normospermia and asthenospermia were evaluated according to their capacity to reach these stages, and their DNA integrity was assessed by acridine orange (AO) staining. We observed a significant difference between normospermia and asthenozoospermia in the ability to achieve the cycle of chromatin decondensation-recondensation. These results correlated with AO staining. The role of human protamine 1 degradation in the decondensation process was evaluated by immunostaining. It was found not to be a prerequisite for the earlier stage of chromatin decondensation and it was not implied in the latest stages of pronuclear development."} {"id": "PMID:1280943", "title": "Neutralizing-enhancing monoclonal antibody recognizes the denatured glycoprotein of viral haemorrhagic septicaemia virus.", "content": "Two monoclonal antibodies (MAbs), 1H10 and 1F10, have been selected against the denatured glycoprotein of the viral haemorrhagic septicaemia virus (VHSV) of salmonids by immunoblotting. Three reference VHSV serotypes (F1, F2, 23.75) and five VHSV isolates from either different host species (trout, salmon, barbel) or geographical locations in Spain reacted with both MAbs by ELISA. In vitro neutralization of all VHSV serotypes but not infectious haematopoietic necrosis virus (IHNV) was obtained only with MAb 1H10. However, when the MAb 1H10 (but not the non-neutralizing Mab 1F10) concentration was below 100 micrograms/ml rather than neutralizing VHSV infectivity, plaque counts increased 2-3-fold. MAb 1H10 is unique in that it has both, an in vitro enhancing infectivity effect (not described yet for VHSV) and it recognizes denatured G protein in contrast to other previously described neutralizing MAbs against VHSV.", "contents": "Neutralizing-enhancing monoclonal antibody recognizes the denatured glycoprotein of viral haemorrhagic septicaemia virus. Two monoclonal antibodies (MAbs), 1H10 and 1F10, have been selected against the denatured glycoprotein of the viral haemorrhagic septicaemia virus (VHSV) of salmonids by immunoblotting. Three reference VHSV serotypes (F1, F2, 23.75) and five VHSV isolates from either different host species (trout, salmon, barbel) or geographical locations in Spain reacted with both MAbs by ELISA. In vitro neutralization of all VHSV serotypes but not infectious haematopoietic necrosis virus (IHNV) was obtained only with MAb 1H10. However, when the MAb 1H10 (but not the non-neutralizing Mab 1F10) concentration was below 100 micrograms/ml rather than neutralizing VHSV infectivity, plaque counts increased 2-3-fold. MAb 1H10 is unique in that it has both, an in vitro enhancing infectivity effect (not described yet for VHSV) and it recognizes denatured G protein in contrast to other previously described neutralizing MAbs against VHSV."} {"id": "PMID:1280944", "title": "Topographical analysis of the G virion of Aleutian mink disease parvovirus with monoclonal antibodies.", "content": "The topography of the Aleutian mink disease parvovirus (ADV) G virion was analyzed with monoclonal antibodies and polyclonal antiserum. There was homology between the two major structural proteins as others have previously reported. Trypsin treatment of the virion with subsequent immunoblotting revealed that VP2 represents the main peptide on the exterior of virion and that VP1 is probably embedded within the capsid. Additional analyses of the trypsin-treated virions showed that VP2 is responsible for binding complement and that it also represents the structural part of the virion that binds to cellular receptors. A third protein, p34, was detected that might represent a third structural polypeptide because of its many unique epitopes relative to the other peptides detected.", "contents": "Topographical analysis of the G virion of Aleutian mink disease parvovirus with monoclonal antibodies. The topography of the Aleutian mink disease parvovirus (ADV) G virion was analyzed with monoclonal antibodies and polyclonal antiserum. There was homology between the two major structural proteins as others have previously reported. Trypsin treatment of the virion with subsequent immunoblotting revealed that VP2 represents the main peptide on the exterior of virion and that VP1 is probably embedded within the capsid. Additional analyses of the trypsin-treated virions showed that VP2 is responsible for binding complement and that it also represents the structural part of the virion that binds to cellular receptors. A third protein, p34, was detected that might represent a third structural polypeptide because of its many unique epitopes relative to the other peptides detected."} {"id": "PMID:1280945", "title": "Genetic characterization of an antigenic subtype of eastern equine encephalomyelitis virus.", "content": "A 1983 human Mississippi isolate of eastern equine encephalomyelitis virus (EEEV), recently identified as an antigenic subtype of the North American variety, was genetically characterized using oligonucleotide fingerprinting and sequencing of viral RNA. This strain was found to be very closely related to other North American EEEV isolates from the same time period. Phylogenetic analysis suggested that this subtype belongs to a single EEEV lineage in North America. Two amino acid substitutions in the E2 envelope glycoprotein, not seen in either other isolates sequenced, probably contributed to the antigenic difference with respect to other EEEV strains. These substitutions include threonine for lysine at position 71, resulting in the addition of a potential N-linked glycosylation site, and lysine for glutamic acid at position 147.", "contents": "Genetic characterization of an antigenic subtype of eastern equine encephalomyelitis virus. A 1983 human Mississippi isolate of eastern equine encephalomyelitis virus (EEEV), recently identified as an antigenic subtype of the North American variety, was genetically characterized using oligonucleotide fingerprinting and sequencing of viral RNA. This strain was found to be very closely related to other North American EEEV isolates from the same time period. Phylogenetic analysis suggested that this subtype belongs to a single EEEV lineage in North America. Two amino acid substitutions in the E2 envelope glycoprotein, not seen in either other isolates sequenced, probably contributed to the antigenic difference with respect to other EEEV strains. These substitutions include threonine for lysine at position 71, resulting in the addition of a potential N-linked glycosylation site, and lysine for glutamic acid at position 147."} {"id": "PMID:1280946", "title": "Human rotavirus strain with unique VP4 neutralization epitopes as a result of natural reassortment between members of the AU-1 and Wa genogroups.", "content": "Human rotavirus strain K8, which possesses unique VP4 neutralization epitopes, was examined by RNA-RNA hybridization to determine its genogroup. While it possessed four gene segments that formed hybrids with strain Wa (a prototype of the Wa genogroup), strain K8 possessed seven gene segments, including gene segment 4, that formed hybrids with strain AU-1 (a prototype of the AU-1 genogroup) which has been shown to share a unique gene 4 allele with feline rotaviruses. These results suggest that strain K8 is an intergenogroup reassortant formed in nature between a member of the Wa genogroup and a member of the AU-1 genogroup.", "contents": "Human rotavirus strain with unique VP4 neutralization epitopes as a result of natural reassortment between members of the AU-1 and Wa genogroups. Human rotavirus strain K8, which possesses unique VP4 neutralization epitopes, was examined by RNA-RNA hybridization to determine its genogroup. While it possessed four gene segments that formed hybrids with strain Wa (a prototype of the Wa genogroup), strain K8 possessed seven gene segments, including gene segment 4, that formed hybrids with strain AU-1 (a prototype of the AU-1 genogroup) which has been shown to share a unique gene 4 allele with feline rotaviruses. These results suggest that strain K8 is an intergenogroup reassortant formed in nature between a member of the Wa genogroup and a member of the AU-1 genogroup."} {"id": "PMID:1280947", "title": "Objective evaluation of the quality of palliation in patients with oesophageal cancer comparing surgery, radiotherapy and intubation.", "content": "The objective of this study was to prospectively evaluate the quality of palliation of 103 patients presenting to a joint oesophageal cancer clinic while recording the outcome in terms of treatment, morbidity, mortality and long-term survival. Twenty-five patients underwent surgical resection (S), 22 radical radiotherapy (RR), 30 palliative radiotherapy (PR), 13 intubation (I) and 13 had no treatment (NT). The quality of palliation was quantified by plotting a score out of 100 on a graph at each visit for Karnofsky performance, severity of pain and swallowing ability, then calculating the area under each curve created using an algorithm, Simpson's discrete approximation. Efficiency of palliation was estimated by comparing the area calculated to the maximum that could be achieved during the time frame being studied. The incidence of stricture (benign and malignant) was 16% after surgery and 50% after radical radiotherapy. Treatment mortality was as follows: RR, 0; S, 1 (4%); PR, 3 (7%); and I, 0. The median survival was 26 months after surgery and 16 months after radical radiotherapy. It was 6 months for palliative radiotherapy, 4 months for intubation and 4 months for no treatment. The difference in swallowing was the only statistical difference in the quality of palliation of patients having surgery and radical radiotherapy, there being no differences in patients having palliative measures.", "contents": "Objective evaluation of the quality of palliation in patients with oesophageal cancer comparing surgery, radiotherapy and intubation. The objective of this study was to prospectively evaluate the quality of palliation of 103 patients presenting to a joint oesophageal cancer clinic while recording the outcome in terms of treatment, morbidity, mortality and long-term survival. Twenty-five patients underwent surgical resection (S), 22 radical radiotherapy (RR), 30 palliative radiotherapy (PR), 13 intubation (I) and 13 had no treatment (NT). The quality of palliation was quantified by plotting a score out of 100 on a graph at each visit for Karnofsky performance, severity of pain and swallowing ability, then calculating the area under each curve created using an algorithm, Simpson's discrete approximation. Efficiency of palliation was estimated by comparing the area calculated to the maximum that could be achieved during the time frame being studied. The incidence of stricture (benign and malignant) was 16% after surgery and 50% after radical radiotherapy. Treatment mortality was as follows: RR, 0; S, 1 (4%); PR, 3 (7%); and I, 0. The median survival was 26 months after surgery and 16 months after radical radiotherapy. It was 6 months for palliative radiotherapy, 4 months for intubation and 4 months for no treatment. The difference in swallowing was the only statistical difference in the quality of palliation of patients having surgery and radical radiotherapy, there being no differences in patients having palliative measures."} {"id": "PMID:1280948", "title": "Learning of a hippocampal-dependent conditioning task changes the binding properties of AMPA receptors in rabbit hippocampus.", "content": "The N-methyl-D-asparate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtypes of glutamate receptors have been shown to play critical roles in various forms of synaptic plasticity (i.e., learning and memory, long-term potentiation). We previously demonstrated that the binding of [3H]AMPA to the AMPA subtype of glutamate receptors was selectively increased in hippocampus following classical conditioning of the rabbit nictitating membrane response in a delay paradigm. We report here that the same effect was observed in a variant of this learning paradigm that requires the participation of the hippocampus, i.e., trace conditioning of the rabbit nictitating membrane. The binding of [3H]TCP (N-[1-(2-thienyl)cyclo-hexyl]-3,4-piperidine) to the NMDA receptor remained unchanged in all the experimental groups tested. Paired presentations of conditioned and unconditioned stimuli resulted in an increased binding of [3H]AMPA, an agonist of the AMPA receptors, in several hippocampal subfields while the binding of an antagonist, [3H]CNQX (6-nitro-7-cyanoquinoxaline-2,3-dione), was decreased. The results suggest that the learning-induced changes in binding of the ligands to the AMPA receptor reflect changes in affinity of the receptor rather than in the number of sites. These results support the hypothesis that changes in hippocampal glutamate receptors are a corollary of synaptic plasticity in certain forms of learning.", "contents": "Learning of a hippocampal-dependent conditioning task changes the binding properties of AMPA receptors in rabbit hippocampus. The N-methyl-D-asparate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) subtypes of glutamate receptors have been shown to play critical roles in various forms of synaptic plasticity (i.e., learning and memory, long-term potentiation). We previously demonstrated that the binding of [3H]AMPA to the AMPA subtype of glutamate receptors was selectively increased in hippocampus following classical conditioning of the rabbit nictitating membrane response in a delay paradigm. We report here that the same effect was observed in a variant of this learning paradigm that requires the participation of the hippocampus, i.e., trace conditioning of the rabbit nictitating membrane. The binding of [3H]TCP (N-[1-(2-thienyl)cyclo-hexyl]-3,4-piperidine) to the NMDA receptor remained unchanged in all the experimental groups tested. Paired presentations of conditioned and unconditioned stimuli resulted in an increased binding of [3H]AMPA, an agonist of the AMPA receptors, in several hippocampal subfields while the binding of an antagonist, [3H]CNQX (6-nitro-7-cyanoquinoxaline-2,3-dione), was decreased. The results suggest that the learning-induced changes in binding of the ligands to the AMPA receptor reflect changes in affinity of the receptor rather than in the number of sites. These results support the hypothesis that changes in hippocampal glutamate receptors are a corollary of synaptic plasticity in certain forms of learning."} {"id": "PMID:1280949", "title": "A rapid technique for visualizing cerebral arteries in rat.", "content": "Intracardiac perfusion with cresyl violet acetate dissolved in 0.9% isotonic saline and dimethyl sulfoxide (DMSO) allows one to visualize the arterial blood supply to the central hemispheres. This technique is especially useful in demonstrating the ramifications of and areas supplied by the middle cerebral artery. Many individual differences in the course traversed by the artery and the distal areas supplied were observed. This technique could prove to be a useful adjunct to neurohistological techniques in studies investigating rodent models of stroke.", "contents": "A rapid technique for visualizing cerebral arteries in rat. Intracardiac perfusion with cresyl violet acetate dissolved in 0.9% isotonic saline and dimethyl sulfoxide (DMSO) allows one to visualize the arterial blood supply to the central hemispheres. This technique is especially useful in demonstrating the ramifications of and areas supplied by the middle cerebral artery. Many individual differences in the course traversed by the artery and the distal areas supplied were observed. This technique could prove to be a useful adjunct to neurohistological techniques in studies investigating rodent models of stroke."} {"id": "PMID:1280950", "title": "Anti-caldesmon monoclonal antibody reverses the inhibition of actomyosin Mg(2+)-ATPase activity by caldesmon.", "content": "Five mouse monoclonal antibodies, CaD 1-5, against chicken gizzard caldesmon were prepared. One of them (CaD4) was characterized by means of immunoblotting and its effect on actomyosin Mg(2+)-ATPase activity. CaD4 recognized the tropomyosin-binding site of caldesmon. CaD4 reversed the caldesmon-induced inhibition of actomyosin Mg(2+)-ATPase activity in a dose-dependent manner. These results suggest that the epitope recognized by CaD4 is an important domain for the function of caldesmon on the actinmyosin interaction in the smooth muscle contraction-relaxation system.", "contents": "Anti-caldesmon monoclonal antibody reverses the inhibition of actomyosin Mg(2+)-ATPase activity by caldesmon. Five mouse monoclonal antibodies, CaD 1-5, against chicken gizzard caldesmon were prepared. One of them (CaD4) was characterized by means of immunoblotting and its effect on actomyosin Mg(2+)-ATPase activity. CaD4 recognized the tropomyosin-binding site of caldesmon. CaD4 reversed the caldesmon-induced inhibition of actomyosin Mg(2+)-ATPase activity in a dose-dependent manner. These results suggest that the epitope recognized by CaD4 is an important domain for the function of caldesmon on the actinmyosin interaction in the smooth muscle contraction-relaxation system."} {"id": "PMID:1280951", "title": "Enhanced expression of type 2C protein phosphatase gene during myogenic differentiation of C3H10T1/2 cells.", "content": "Type 2C phosphatase is one of the four major protein serine.threonine phosphatases (types 1, 2A, 2B and 2C). The mRNA level of the enzyme protein was 11.5 times higher in mouse skeletal muscle than in undifferentiated mesenchymal cells (C3H10T1/2). The mRNA level was enhanced 4.2-fold in accordance with the differentiation of C3H10T1/2 cells into myoblasts induced by transfection with a MyoD1 expression vector, and this high level was maintained in terminally differentiated myotubes. Furthermore, type 2C phosphatase activity in both myoblast and myotube fractions was slightly higher than in control C3H10T1/2 cells. These results indicate that the expression of type 2C phosphatase gene is enhanced during the course of myogenic differentiation.", "contents": "Enhanced expression of type 2C protein phosphatase gene during myogenic differentiation of C3H10T1/2 cells. Type 2C phosphatase is one of the four major protein serine.threonine phosphatases (types 1, 2A, 2B and 2C). The mRNA level of the enzyme protein was 11.5 times higher in mouse skeletal muscle than in undifferentiated mesenchymal cells (C3H10T1/2). The mRNA level was enhanced 4.2-fold in accordance with the differentiation of C3H10T1/2 cells into myoblasts induced by transfection with a MyoD1 expression vector, and this high level was maintained in terminally differentiated myotubes. Furthermore, type 2C phosphatase activity in both myoblast and myotube fractions was slightly higher than in control C3H10T1/2 cells. These results indicate that the expression of type 2C phosphatase gene is enhanced during the course of myogenic differentiation."} {"id": "PMID:1280952", "title": "Platelet cAMP and cGMP in essential hypertension.", "content": "Vasodilator substances released in the blood vessel wall, such as the endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2), may participate in the regulation of arterial blood pressure. However, their role in the pathogenesis of human essential hypertension to date remains unclear. For some of these factors affecting vascular smooth muscle cells, blood platelets represent a second target tissue. Thus, EDRF and PGI2 inactivate platelets by stimulation of cyclic guanosine-5'-monophosphate (cGMP) and cyclic adenosine-5'-monophosphate (cAMP) synthesis, respectively. In the present study, platelet cAMP (n = 68) and cGMP (n = 60) were determined in a control group of healthy subjects (C) and in 12 patients with untreated essential hypertension (EH). In the control group, platelet cAMP and cGMP content averaged 13.52 +/- 0.38 and 1.48 +/- 0.06 pmol/10(9) platelets and no dependence of either variable on sex or age could be established. Furthermore, cGMP levels were similar in EH as compared to the control group (1.38 +/- 0.11 pmol/10(9) platelets). However, intracellular concentrations of cAMP were significantly lower in EH as compared to C (11.22 +/- 1.37 pmol/10(9) platelets; P < .01). In addition, we investigated the stimulatory effect on cAMP of the stable PGI2 analog iloprost (10(-9), 5 x 10(-9), 10(-8), 5 x 10(-8) mol/L) in the platelets of 12 control subjects (C12) and EH.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Platelet cAMP and cGMP in essential hypertension. Vasodilator substances released in the blood vessel wall, such as the endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2), may participate in the regulation of arterial blood pressure. However, their role in the pathogenesis of human essential hypertension to date remains unclear. For some of these factors affecting vascular smooth muscle cells, blood platelets represent a second target tissue. Thus, EDRF and PGI2 inactivate platelets by stimulation of cyclic guanosine-5'-monophosphate (cGMP) and cyclic adenosine-5'-monophosphate (cAMP) synthesis, respectively. In the present study, platelet cAMP (n = 68) and cGMP (n = 60) were determined in a control group of healthy subjects (C) and in 12 patients with untreated essential hypertension (EH). In the control group, platelet cAMP and cGMP content averaged 13.52 +/- 0.38 and 1.48 +/- 0.06 pmol/10(9) platelets and no dependence of either variable on sex or age could be established. Furthermore, cGMP levels were similar in EH as compared to the control group (1.38 +/- 0.11 pmol/10(9) platelets). However, intracellular concentrations of cAMP were significantly lower in EH as compared to C (11.22 +/- 1.37 pmol/10(9) platelets; P < .01). In addition, we investigated the stimulatory effect on cAMP of the stable PGI2 analog iloprost (10(-9), 5 x 10(-9), 10(-8), 5 x 10(-8) mol/L) in the platelets of 12 control subjects (C12) and EH.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1280953", "title": "Ultrastructural study of the choroid plexus of spontaneously hypertensive rats.", "content": "We previously gave an account of an increased ion transport activity in choroid plexus from spontaneously hypertensive rats. We have since examined this organ in scanning and transmission electronic microscopy. In the choroid plexus from young spontaneously hypertensive rats, the epithelial cells showed the following: a partial loss of the brush border and infoldings of basolateral membranes, an increased number of Golgi apparatus, vesicles, and mitochondria, and an activated nucleus. In adult hypertensive rats, the mitochondria had increased in number and tended to fill the cytoplasma while the nuclei had returned to a resting level. These ultrastructural changes furthermore suggest an increased secretory activity in the choroid plexus in spontaneously hypertensive rats.", "contents": "Ultrastructural study of the choroid plexus of spontaneously hypertensive rats. We previously gave an account of an increased ion transport activity in choroid plexus from spontaneously hypertensive rats. We have since examined this organ in scanning and transmission electronic microscopy. In the choroid plexus from young spontaneously hypertensive rats, the epithelial cells showed the following: a partial loss of the brush border and infoldings of basolateral membranes, an increased number of Golgi apparatus, vesicles, and mitochondria, and an activated nucleus. In adult hypertensive rats, the mitochondria had increased in number and tended to fill the cytoplasma while the nuclei had returned to a resting level. These ultrastructural changes furthermore suggest an increased secretory activity in the choroid plexus in spontaneously hypertensive rats."} {"id": "PMID:1280954", "title": "Three essential promoter elements mediate tumour necrosis factor and interleukin-1 activation of the granulocyte-colony stimulating factor gene.", "content": "Granulocyte-colony stimulating factor (G-CSF) is a haemopoietic growth factor produced by mesenchymal cells but not T lymphocytes after stimulation with specific cytokines or mitogens. A 330 bp promoter fragment of the human G-CSF gene induced reporter gene expression in human embryonic lung fibroblasts in response to tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). The same promoter fragment was not active in Jurkat T cells nor did it respond to phorbol ester in either cell type. At least three distinct elements, the CK-1 sequence, a decanucleotide present in haemopoietic growth factor genes, an NF-IL-6 consensus sequence and a consensus octamer sequence, were essential in the G-CSF promoter for TNF-alpha and IL-1 beta response. Mutation of any of these sequences abolished promoter function. In contrast, mutation of two other consensus protein binding sequences, i.e. a Pu-1 site and a CK-2-like sequence, did not eliminate promoter function. Both the CK-1 and octamer sequences acted independently as TNF-alpha and IL-1 beta responsive elements upstream of a heterologous promoter. The response of the octamer sequence and the 330 bp promoter but not the CK-1 sequence was greater with IL-1 beta than TNF-alpha reflecting a similar response of the endogenous gene.", "contents": "Three essential promoter elements mediate tumour necrosis factor and interleukin-1 activation of the granulocyte-colony stimulating factor gene. Granulocyte-colony stimulating factor (G-CSF) is a haemopoietic growth factor produced by mesenchymal cells but not T lymphocytes after stimulation with specific cytokines or mitogens. A 330 bp promoter fragment of the human G-CSF gene induced reporter gene expression in human embryonic lung fibroblasts in response to tumor necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). The same promoter fragment was not active in Jurkat T cells nor did it respond to phorbol ester in either cell type. At least three distinct elements, the CK-1 sequence, a decanucleotide present in haemopoietic growth factor genes, an NF-IL-6 consensus sequence and a consensus octamer sequence, were essential in the G-CSF promoter for TNF-alpha and IL-1 beta response. Mutation of any of these sequences abolished promoter function. In contrast, mutation of two other consensus protein binding sequences, i.e. a Pu-1 site and a CK-2-like sequence, did not eliminate promoter function. Both the CK-1 and octamer sequences acted independently as TNF-alpha and IL-1 beta responsive elements upstream of a heterologous promoter. The response of the octamer sequence and the 330 bp promoter but not the CK-1 sequence was greater with IL-1 beta than TNF-alpha reflecting a similar response of the endogenous gene."} {"id": "PMID:1280955", "title": "Immunodominant epitopes of HIV-1 p17 and p24.", "content": "Immunodominant antibody-binding sites were mapped using overlapping synthetic peptides of the structural proteins p17 and p24 of human immunodeficiency virus type 1 (HIV-1). Using sera from HIV-1-infected individuals at a variety of disease states, three major epitopes were identified within p17 and one within p24. Antibodies which recognized these epitopes were present in all risk groups throughout all stages of HIV infection, regardless of the presence of high levels of serum p24 antigen.", "contents": "Immunodominant epitopes of HIV-1 p17 and p24. Immunodominant antibody-binding sites were mapped using overlapping synthetic peptides of the structural proteins p17 and p24 of human immunodeficiency virus type 1 (HIV-1). Using sera from HIV-1-infected individuals at a variety of disease states, three major epitopes were identified within p17 and one within p24. Antibodies which recognized these epitopes were present in all risk groups throughout all stages of HIV infection, regardless of the presence of high levels of serum p24 antigen."} {"id": "PMID:1280956", "title": "Mapping of linear B-cell epitopes on the major core protein p24 of human immunodeficiency virus type 1 (HIV-1).", "content": "Three murine monoclonal antibodies (MAbs) F5-2, F5-4, and F5-16 defining three different epitopes on the major core protein p24 of the human immunodeficiency virus type 1 (HIV-1) were epitope mapped using a random fragment expression library representing the p17- and p24-encoding part of the gag open reading frame. F5-2 defined an epitope within amino acids (aa) 14-23 at the N-terminus of p24, and F5-4 defined an epitope within aa 153-174 in the C-terminus of p24. F5-16 did not recognize any of the fusion proteins produced by the expression library indicating that this MAb defines a true conformational epitope on p24. Since the N-terminus of p24 has been reported to be immunosilent in humans, 356 HIV-1 antibody-positive serum samples were tested for reactivity against the region of p24 defined by F5-2. More than one third of the samples recognized this region indicating that it is immunoreactive and, further, the presence of antibodies against this region was associated with a reduced CD4 cell count.", "contents": "Mapping of linear B-cell epitopes on the major core protein p24 of human immunodeficiency virus type 1 (HIV-1). Three murine monoclonal antibodies (MAbs) F5-2, F5-4, and F5-16 defining three different epitopes on the major core protein p24 of the human immunodeficiency virus type 1 (HIV-1) were epitope mapped using a random fragment expression library representing the p17- and p24-encoding part of the gag open reading frame. F5-2 defined an epitope within amino acids (aa) 14-23 at the N-terminus of p24, and F5-4 defined an epitope within aa 153-174 in the C-terminus of p24. F5-16 did not recognize any of the fusion proteins produced by the expression library indicating that this MAb defines a true conformational epitope on p24. Since the N-terminus of p24 has been reported to be immunosilent in humans, 356 HIV-1 antibody-positive serum samples were tested for reactivity against the region of p24 defined by F5-2. More than one third of the samples recognized this region indicating that it is immunoreactive and, further, the presence of antibodies against this region was associated with a reduced CD4 cell count."} {"id": "PMID:1280957", "title": "Direct observation of reverse transcriptases by scanning tunneling microscopy.", "content": "First images on a nanometer scale of reverse transcriptases (RT) of the human immunodeficiency virus (HIV-1) and of the Moloney murine leukemia virus (MuLV) obtained by scanning tunneling microscopy (STM) are reported. The common feature of the observed molecules is a ring-type or horseshoe shape with hole diameters of approximately 30 A. The STM images are compared with high resolution transmission electron microscopy (TEM) and existing structure predictions. The similarities of the structural data obtained by STM and TEM and their agreement with the structure prediction for the RT of HIV-1 shows the principal possibility to image such biomolecules by STM.", "contents": "Direct observation of reverse transcriptases by scanning tunneling microscopy. First images on a nanometer scale of reverse transcriptases (RT) of the human immunodeficiency virus (HIV-1) and of the Moloney murine leukemia virus (MuLV) obtained by scanning tunneling microscopy (STM) are reported. The common feature of the observed molecules is a ring-type or horseshoe shape with hole diameters of approximately 30 A. The STM images are compared with high resolution transmission electron microscopy (TEM) and existing structure predictions. The similarities of the structural data obtained by STM and TEM and their agreement with the structure prediction for the RT of HIV-1 shows the principal possibility to image such biomolecules by STM."} {"id": "PMID:1280961", "title": "[Multicentric study of 143 cases of resection of the proximal carpal bones].", "content": "Proximal row carpectomy is an old procedure but the good results published in the literature, it still has bad reputation. The authors conducted a retrospective multicentric study in 143 patients, 128 of whom were post-traumatic cases. And results were good in terms of pain relief. Increase in grip strength was observed in 80% of cases. Wrist range of motion was not improved by resection. The results were not predicted by preoperative status. No prognostic factor could be defined on the basis of study.", "contents": "[Multicentric study of 143 cases of resection of the proximal carpal bones]. Proximal row carpectomy is an old procedure but the good results published in the literature, it still has bad reputation. The authors conducted a retrospective multicentric study in 143 patients, 128 of whom were post-traumatic cases. And results were good in terms of pain relief. Increase in grip strength was observed in 80% of cases. Wrist range of motion was not improved by resection. The results were not predicted by preoperative status. No prognostic factor could be defined on the basis of study."} {"id": "PMID:1280962", "title": "[Operative technique of arthroplastic resection of the three proximal bones].", "content": "Proximal row carpectomy is a controversial operative technique for difficult wrist problems. Based upon resection of bones, it represents in fact a reconstructive technique of a new joint. The majors steps of the technique are described in detail.", "contents": "[Operative technique of arthroplastic resection of the three proximal bones]. Proximal row carpectomy is a controversial operative technique for difficult wrist problems. Based upon resection of bones, it represents in fact a reconstructive technique of a new joint. The majors steps of the technique are described in detail."} {"id": "PMID:1280963", "title": "[Resection of the proximal carpal bones in the sequelae of scaphoid fractures].", "content": "Proximal row carpectomy has precise indications in cases of severe sequelae of scaphoid fractures. This procedure may be indicated either as first-line treatment in a case of advanced pseudarthrosis with osteoarthritis, particularly radio-scaphoid, or secondarily after scaphoid pseudarthrosis has been unsuccessfully treated by other methods. It is essential to make sure that the head of the capitatum and the radial surface of the lunate bone have a satisfactory appearance on plain X-rays, MRI and occasionally arthroscopy. The overall results of this operation which retains wrist movements and which also preserves a good grip strength are very encouraging, as demonstrated by the series of 48 cases of sequelae of scAphoid fractures treated by this technique.", "contents": "[Resection of the proximal carpal bones in the sequelae of scaphoid fractures]. Proximal row carpectomy has precise indications in cases of severe sequelae of scaphoid fractures. This procedure may be indicated either as first-line treatment in a case of advanced pseudarthrosis with osteoarthritis, particularly radio-scaphoid, or secondarily after scaphoid pseudarthrosis has been unsuccessfully treated by other methods. It is essential to make sure that the head of the capitatum and the radial surface of the lunate bone have a satisfactory appearance on plain X-rays, MRI and occasionally arthroscopy. The overall results of this operation which retains wrist movements and which also preserves a good grip strength are very encouraging, as demonstrated by the series of 48 cases of sequelae of scAphoid fractures treated by this technique."} {"id": "PMID:1280964", "title": "[Resection of the proximal carpal bones versus partial arthrodesis in carpal instability].", "content": "Ten resections of the proximal row of carpal bones and 42 partial arthrodese were performed for carpal instability. Whenever possible, the authors prefer the second operation. This choice is often made during the operation and essentially depends on the presence of radio-scaphoid osteoarthritis and the condition of the cartilage of the head of the capitatum.", "contents": "[Resection of the proximal carpal bones versus partial arthrodesis in carpal instability]. Ten resections of the proximal row of carpal bones and 42 partial arthrodese were performed for carpal instability. Whenever possible, the authors prefer the second operation. This choice is often made during the operation and essentially depends on the presence of radio-scaphoid osteoarthritis and the condition of the cartilage of the head of the capitatum."} {"id": "PMID:1280966", "title": "[Emergency resection of the proximal carpal bones].", "content": "Nine cases of emergency proximal row carpectomy are analysed. In 3 cases, the resection was performed in the context of transcarpal amputation in which the bone shortening obtained by resection allowed revascularisation without a flap. The functional result was poor because of the severity of the initial lesion. In the other 6 cases, consisting of proximal row bone defects or so-called intreatable fracture-dislocations, the results in terms of pain, range of movement and strength were similar to those obtained with elective operations.", "contents": "[Emergency resection of the proximal carpal bones]. Nine cases of emergency proximal row carpectomy are analysed. In 3 cases, the resection was performed in the context of transcarpal amputation in which the bone shortening obtained by resection allowed revascularisation without a flap. The functional result was poor because of the severity of the initial lesion. In the other 6 cases, consisting of proximal row bone defects or so-called intreatable fracture-dislocations, the results in terms of pain, range of movement and strength were similar to those obtained with elective operations."} {"id": "PMID:1280967", "title": "[Wrist arthrodesis: alternative to resection of the proximal carpal bones?].", "content": "The results of a series of 36 post-traumatic radio-carpal arthrodeses were compared with those of the series of resection of the first row of carpal bones reported during the round table. The advantages and disadvantages of both procedures were discussed. Arthrodesis results in: 1) loss of grip strength in all cases, averaging 41%; 2) persistent pain in 78% of cases; 3) impairment of function resulting from blocking of the wrist. After the procedure, average time off work is 15 months, level of permanent disability was 30%, and 20% of patients returned to their previous jobs. These figures could be used as arguments against arthrodesis. However, they must be taken in context: final arthrodesis, usually performed on manual workers, is often chosen when resection of the first row of carpal bones would obviously be insufficient, for example, when severe arthritis of the head of the capitate is present.", "contents": "[Wrist arthrodesis: alternative to resection of the proximal carpal bones?]. The results of a series of 36 post-traumatic radio-carpal arthrodeses were compared with those of the series of resection of the first row of carpal bones reported during the round table. The advantages and disadvantages of both procedures were discussed. Arthrodesis results in: 1) loss of grip strength in all cases, averaging 41%; 2) persistent pain in 78% of cases; 3) impairment of function resulting from blocking of the wrist. After the procedure, average time off work is 15 months, level of permanent disability was 30%, and 20% of patients returned to their previous jobs. These figures could be used as arguments against arthrodesis. However, they must be taken in context: final arthrodesis, usually performed on manual workers, is often chosen when resection of the first row of carpal bones would obviously be insufficient, for example, when severe arthritis of the head of the capitate is present."} {"id": "PMID:1280968", "title": "[Denervation of the wrist].", "content": "Fifty patients with wrist arthritis mainly secondary to a scaphoid pseudarthrosis (44%) or a Kienb\u00f6ck disease (22%) were operated on by one surgeon by \"total\" denervation. With a post-operative follow up of 5 years, pain, strength and range of movement were reviewed. Four complications are by means of stressed: one painful neuroma and three radial nerve paresthesiae. 72% of the patients had pain improvement with an average of 72 points on a scale of 100 points. Strength and range of movement were not significantly improved.", "contents": "[Denervation of the wrist]. Fifty patients with wrist arthritis mainly secondary to a scaphoid pseudarthrosis (44%) or a Kienb\u00f6ck disease (22%) were operated on by one surgeon by \"total\" denervation. With a post-operative follow up of 5 years, pain, strength and range of movement were reviewed. Four complications are by means of stressed: one painful neuroma and three radial nerve paresthesiae. 72% of the patients had pain improvement with an average of 72 points on a scale of 100 points. Strength and range of movement were not significantly improved."} {"id": "PMID:1280969", "title": "[Experimental proximal carpectomy. Biodynamics].", "content": "Proximal carpectomy was performed in 10 fresh cadavre wrists. Dynamic x-rays were taken and the forces necessary to obtain different movements before and after the operation were measured. Comparison of these parameters clearly defines the advantages and limitations of carpectomy and indicates the reasons.", "contents": "[Experimental proximal carpectomy. Biodynamics]. Proximal carpectomy was performed in 10 fresh cadavre wrists. Dynamic x-rays were taken and the forces necessary to obtain different movements before and after the operation were measured. Comparison of these parameters clearly defines the advantages and limitations of carpectomy and indicates the reasons."} {"id": "PMID:1280970", "title": "[Biomechanic considerations in wrist prostheses].", "content": "At the present time, in disorders of the wrist, avulsion of the first carpal row is the most commonly used technique as a last resort. However, there are many wrist prostheses, which are reviewed here. Roughly, they belong to two families: the three axis prostheses (spherical) that cannot transmit to the hand the pronation supination torque, because of their geometrical characteristics, and the two axis prostheses (universal joint) that are able to transmit this movement. The characteristics of future prostheses must include: based on the \"universal joint\" principle, occupy minimum space, isometric, maintain tendon tension, an axis identical to the true axis of the wrist, to maintain the hand in line with the forearm, fixed without cement but, not shortened with time, possibilities of mechanical flexibility immediately and lastingly stable, to be easily replaced modularly. This ideal prosthesis will certainly exist one day and will take the place of the first carpal row avulsion. In the meantime, this technique will still have a long use.", "contents": "[Biomechanic considerations in wrist prostheses]. At the present time, in disorders of the wrist, avulsion of the first carpal row is the most commonly used technique as a last resort. However, there are many wrist prostheses, which are reviewed here. Roughly, they belong to two families: the three axis prostheses (spherical) that cannot transmit to the hand the pronation supination torque, because of their geometrical characteristics, and the two axis prostheses (universal joint) that are able to transmit this movement. The characteristics of future prostheses must include: based on the \"universal joint\" principle, occupy minimum space, isometric, maintain tendon tension, an axis identical to the true axis of the wrist, to maintain the hand in line with the forearm, fixed without cement but, not shortened with time, possibilities of mechanical flexibility immediately and lastingly stable, to be easily replaced modularly. This ideal prosthesis will certainly exist one day and will take the place of the first carpal row avulsion. In the meantime, this technique will still have a long use."} {"id": "PMID:1280971", "title": "[Dorsal tenolysis and arthrolysis of the proximal interphalangeal joint. 19 cases].", "content": "18 patients suffering from PIP stiffness in extension were treated by dorsal teno-arthrolysis. PIP joint stiffness was due to 3 cases of fracture of P1, 2 cases of fracture of P2, 2 cases of extensor tendons, 8 fractures of P1 associated with section of the extensor tendon, 2 cases of PIP closed trauma (1 sprain, 1 dislocation), and 2 crush injuries of the extensor tendon at the PIP joint. The surgical technique combined a dorsal sinuous approach, tenolysis of the extensor tendon on the dorsum of first phalanx dorsal capsulotomy, and more rarely (3 cases), section of collateral ligaments. The mean pre-operative active flexion was 44 degrees and the mean post operative active flexion was 78 degrees, which represents a gain of 34 degrees of active movement. Thanks to a classification which incorporates the range of active flexion in PIP joint, and the lock of active extension we rated 3 results as excellent, 4 as good, 8 as useful and 4 as insufficient. We therefore improved the range of movement in 15 out of 19 cases, which seams very encouraging.", "contents": "[Dorsal tenolysis and arthrolysis of the proximal interphalangeal joint. 19 cases]. 18 patients suffering from PIP stiffness in extension were treated by dorsal teno-arthrolysis. PIP joint stiffness was due to 3 cases of fracture of P1, 2 cases of fracture of P2, 2 cases of extensor tendons, 8 fractures of P1 associated with section of the extensor tendon, 2 cases of PIP closed trauma (1 sprain, 1 dislocation), and 2 crush injuries of the extensor tendon at the PIP joint. The surgical technique combined a dorsal sinuous approach, tenolysis of the extensor tendon on the dorsum of first phalanx dorsal capsulotomy, and more rarely (3 cases), section of collateral ligaments. The mean pre-operative active flexion was 44 degrees and the mean post operative active flexion was 78 degrees, which represents a gain of 34 degrees of active movement. Thanks to a classification which incorporates the range of active flexion in PIP joint, and the lock of active extension we rated 3 results as excellent, 4 as good, 8 as useful and 4 as insufficient. We therefore improved the range of movement in 15 out of 19 cases, which seams very encouraging."} {"id": "PMID:1280972", "title": "[Correlation between Dupuytren's disease and arcus senilis: is dyslipidemia a common etiopathological factor?].", "content": "Because of the frequent presence of corneal arcus senilis in patients affected by Dupuytren's disease in order to evaluate this association, the authors conducted a biomicroscopic examination of the cornea in 336 patients treated surgically for Dupuytren's disease, at the Hand Surgery Unit of the University of Modena from November 1985 to December 1989. They observed corneal arcus senilis in 259 patients, i.e. in 77.1% of patients with Dupuytren's disease. Due to the statistically significant correlation between arcus senilis and hyperlipidemia as reported by Tschetter (1980) and Felder (1981), the Authors collected a blood sample from all 336 patients to evaluate serum cholesterol and tryglicerides. This study revealed a dyslipidemia in 54.8% of patients with Dupuytren's disease and in 60.2% of patients suffering from both Dupuytren's disease and arcus senilis. Because of the high frequency of dislipidemia in patients with Dupuytren's disease and arcus senilis, which are apparently two well-distinguished disease, the authors suggest that a lipid disorder may be a common aetiopathogenic factor. In particular, in favour of the possible role of hyperlipidemia in Dupuytren's disease, Electron Microscope Studies revealed lipid inclusions within fibroblasts and in the extracellular connective tissue of all pathologic palmar aponeurosis from 11 patients with Dupuytren's disease: these lipid inclusions were never seen in the normal aponeurosis taken from 5 control patients treated for traumatic palmar injuries.", "contents": "[Correlation between Dupuytren's disease and arcus senilis: is dyslipidemia a common etiopathological factor?]. Because of the frequent presence of corneal arcus senilis in patients affected by Dupuytren's disease in order to evaluate this association, the authors conducted a biomicroscopic examination of the cornea in 336 patients treated surgically for Dupuytren's disease, at the Hand Surgery Unit of the University of Modena from November 1985 to December 1989. They observed corneal arcus senilis in 259 patients, i.e. in 77.1% of patients with Dupuytren's disease. Due to the statistically significant correlation between arcus senilis and hyperlipidemia as reported by Tschetter (1980) and Felder (1981), the Authors collected a blood sample from all 336 patients to evaluate serum cholesterol and tryglicerides. This study revealed a dyslipidemia in 54.8% of patients with Dupuytren's disease and in 60.2% of patients suffering from both Dupuytren's disease and arcus senilis. Because of the high frequency of dislipidemia in patients with Dupuytren's disease and arcus senilis, which are apparently two well-distinguished disease, the authors suggest that a lipid disorder may be a common aetiopathogenic factor. In particular, in favour of the possible role of hyperlipidemia in Dupuytren's disease, Electron Microscope Studies revealed lipid inclusions within fibroblasts and in the extracellular connective tissue of all pathologic palmar aponeurosis from 11 patients with Dupuytren's disease: these lipid inclusions were never seen in the normal aponeurosis taken from 5 control patients treated for traumatic palmar injuries."} {"id": "PMID:1280973", "title": "[Distal radio-ulnar prosthesis].", "content": "Many procedures have been proposed for the treatment of traumatic painful instabilities of the Distal Radio-Ulnar Joint (DRUJ). Moore-Darrach, Milch, Baldwin, Bowers, Kapandji-Sauv\u00e9. Except for the Milch procedure, the risk of painful instability of the ulnar stump is real, but not very frequent if the technique is correctly applied. When this complication occurs, the best way to ensure the ulnar stump stabilization is mechanical, by mean of a DRUJ Prosthesis which we were the first to imagine and build. Used in two cases, with or without remnant ulnar head, these two types of prosthesis seem to have been favourable. Obviously, it is too early to know the final value of this prosthesis, based only on two cases, but it seemed important to make it known as an additional possibility in the treatment of the DRUJ problems. These two types of prosthesis are conceived on original principles: cementless fixation but with screws and nuts giving immediate and definitive stability and allowing a fast rehabilitation. The articular pieces are composite, metal on H.D. Polythylene. The articular surface is spherical permitting all the mobilities of this complex joint. The two articular surfaces are supported by two pieces: the proximal part, holding a hollow hemisphere, inserted in the ulna and the same for the two types of prosthesis, and a distal part, holding the sphere; this part is different according to the type of the prosthesis. We are well aware that in time and with clinical experience, some of its secondary characteristics will evolve, mainly its fixation system. At the present time this prosthesis is indicated in two \"second look\" situations: painful ulnar stump instability after a Kapandji-Sauv\u00e9 procedure, and after a Moore-Darrach procedure. Perhaps it will be used in unstable stumps after a Bowers procedure? It is possible that this prosthesis will be used primarlly in the future when its reliability has been definitively established. We are working towards this objective.", "contents": "[Distal radio-ulnar prosthesis]. Many procedures have been proposed for the treatment of traumatic painful instabilities of the Distal Radio-Ulnar Joint (DRUJ). Moore-Darrach, Milch, Baldwin, Bowers, Kapandji-Sauv\u00e9. Except for the Milch procedure, the risk of painful instability of the ulnar stump is real, but not very frequent if the technique is correctly applied. When this complication occurs, the best way to ensure the ulnar stump stabilization is mechanical, by mean of a DRUJ Prosthesis which we were the first to imagine and build. Used in two cases, with or without remnant ulnar head, these two types of prosthesis seem to have been favourable. Obviously, it is too early to know the final value of this prosthesis, based only on two cases, but it seemed important to make it known as an additional possibility in the treatment of the DRUJ problems. These two types of prosthesis are conceived on original principles: cementless fixation but with screws and nuts giving immediate and definitive stability and allowing a fast rehabilitation. The articular pieces are composite, metal on H.D. Polythylene. The articular surface is spherical permitting all the mobilities of this complex joint. The two articular surfaces are supported by two pieces: the proximal part, holding a hollow hemisphere, inserted in the ulna and the same for the two types of prosthesis, and a distal part, holding the sphere; this part is different according to the type of the prosthesis. We are well aware that in time and with clinical experience, some of its secondary characteristics will evolve, mainly its fixation system. At the present time this prosthesis is indicated in two \"second look\" situations: painful ulnar stump instability after a Kapandji-Sauv\u00e9 procedure, and after a Moore-Darrach procedure. Perhaps it will be used in unstable stumps after a Bowers procedure? It is possible that this prosthesis will be used primarlly in the future when its reliability has been definitively established. We are working towards this objective."} {"id": "PMID:1280974", "title": "[Trismus-pseudocamptodactyly syndrome: presentation and genealogy of a new European case].", "content": "The trismus pseudocamptodactyly syndrome also called Hecht syndrome or Dutch-Kentucky syndrome is characterized by loss of the ability to fully open the mouth (trismus) and a finger contracture with progressive flexion of the fingers upon extension of the wrist (pseudocamptodactyly). Deformities of the foot may be associated e.g. hammer and claw toes, tightening of the muscles of the posterior part of the leg producing an equinovarus foot. The authors presents two affected individuals from one family from which nine members had some involvement. The expression of the syndrome may vary. The pattern of the finger contracture is specific. The inheritance is autosomal dominant.", "contents": "[Trismus-pseudocamptodactyly syndrome: presentation and genealogy of a new European case]. The trismus pseudocamptodactyly syndrome also called Hecht syndrome or Dutch-Kentucky syndrome is characterized by loss of the ability to fully open the mouth (trismus) and a finger contracture with progressive flexion of the fingers upon extension of the wrist (pseudocamptodactyly). Deformities of the foot may be associated e.g. hammer and claw toes, tightening of the muscles of the posterior part of the leg producing an equinovarus foot. The authors presents two affected individuals from one family from which nine members had some involvement. The expression of the syndrome may vary. The pattern of the finger contracture is specific. The inheritance is autosomal dominant."} {"id": "PMID:1280975", "title": "Comparative histological overview of the chemical coding of the pulmonary neuroepithelial endocrine system in health and disease.", "content": "Pulmonary neuroepithelial endocrine cells have been shown to contain serotonin-immunoreactivity in almost every species studied. Regulatory peptides, of which at least ten have been reported so far, were mostly only demonstrated in a number of the investigated species or in a subpopulation of neuroepithelial endocrine cells. Calcitonin gene-related peptide, calcitonin, bombesin/gastrin-releasing peptide, enkephalin, somatostatin, substance P, cholecystokinin and polypeptide YY were found in normal lung tissues, whereas ACTH and several other bioactive substances should be regarded as ectopic. The human pulmonary neuroepithelial endocrine system seems to harbour the largest spectrum of bioactive mediators. The distribution patterns of bioactive substances in various subpopulations of solitary neuroepithelial endocrine cells or neuroepithelial bodies and in different cells of a single neuroepithelial body reveal a great complexity. Therefore, further research is needed to elucidate the chemical coding of this system.", "contents": "Comparative histological overview of the chemical coding of the pulmonary neuroepithelial endocrine system in health and disease. Pulmonary neuroepithelial endocrine cells have been shown to contain serotonin-immunoreactivity in almost every species studied. Regulatory peptides, of which at least ten have been reported so far, were mostly only demonstrated in a number of the investigated species or in a subpopulation of neuroepithelial endocrine cells. Calcitonin gene-related peptide, calcitonin, bombesin/gastrin-releasing peptide, enkephalin, somatostatin, substance P, cholecystokinin and polypeptide YY were found in normal lung tissues, whereas ACTH and several other bioactive substances should be regarded as ectopic. The human pulmonary neuroepithelial endocrine system seems to harbour the largest spectrum of bioactive mediators. The distribution patterns of bioactive substances in various subpopulations of solitary neuroepithelial endocrine cells or neuroepithelial bodies and in different cells of a single neuroepithelial body reveal a great complexity. Therefore, further research is needed to elucidate the chemical coding of this system."} {"id": "PMID:1280977", "title": "Selenium metabolism and glutathione peroxidase activity in cultured human lymphoblasts. Effects of transsulfuration defects and pyridoxal phosphate.", "content": "The metabolism of selenite, selenocysteine (SeCys), and selenomethionine (SeMet) was studied in three human lymphoblast cell lines with defects in the transsulfuration pathway and in control cells without this defect. There were very little differences in the induction of glutathione peroxidase (GPX) activity by selenite and SeCys among these cells. However, markedly higher levels of SeMet were required to induce GPX activity in transsulfuration defective cells than in control cells. Surprisingly, the addition of pyridoxal phosphate (PLP) to the media resulted in elevated GPX activity in all cells regardless of the chemical form of Se used. There is no explanation for this effect of PLP, but it is not through direct reaction with GPX or on the alteration of sulfhydryl groups.", "contents": "Selenium metabolism and glutathione peroxidase activity in cultured human lymphoblasts. Effects of transsulfuration defects and pyridoxal phosphate. The metabolism of selenite, selenocysteine (SeCys), and selenomethionine (SeMet) was studied in three human lymphoblast cell lines with defects in the transsulfuration pathway and in control cells without this defect. There were very little differences in the induction of glutathione peroxidase (GPX) activity by selenite and SeCys among these cells. However, markedly higher levels of SeMet were required to induce GPX activity in transsulfuration defective cells than in control cells. Surprisingly, the addition of pyridoxal phosphate (PLP) to the media resulted in elevated GPX activity in all cells regardless of the chemical form of Se used. There is no explanation for this effect of PLP, but it is not through direct reaction with GPX or on the alteration of sulfhydryl groups."} {"id": "PMID:1280978", "title": "Selenium in the central nervous system of rats exposed to 75-Se L-selenomethionine and sodium selenite.", "content": "The aim of the present study is to investigate the accumulation and retention of organic and inorganic selenium in the central nervous system (CNS) of the rat. Selenium accumulation was investigated after oral treatment (3.0 mg Se/L drinking water) or ip injection (1.7 mg Se/kg body wt) of rats exposed to 75-Se L-selenomethionine (SeMeth) or sodium selenite (NaSe). Significant higher concentrations were observed after exposure to organic compared to inorganic selenium after oral as well as ip administration. Highest concentrations in both experiments were observed in cerebellum followed by the nearly identical levels in the cerebral hemisphere and spinal cord independent of the chemical form of selenium or the route of administration. The difference in concentrations observed between the different parts of the CNS investigated in each group were, however, not significant. Retention of selenium in the CNS was investigated after a single ip injection (1.7 mg Se/kg body wt) of 75-Se SeMeth or NaSe. In both groups, we observed an initial fast excretion phase followed by a slower excretion phase resembling a first-order reaction. Organic selenium disappeared much slower from all parts of the central nervous system compared to NaSe after a single injection.", "contents": "Selenium in the central nervous system of rats exposed to 75-Se L-selenomethionine and sodium selenite. The aim of the present study is to investigate the accumulation and retention of organic and inorganic selenium in the central nervous system (CNS) of the rat. Selenium accumulation was investigated after oral treatment (3.0 mg Se/L drinking water) or ip injection (1.7 mg Se/kg body wt) of rats exposed to 75-Se L-selenomethionine (SeMeth) or sodium selenite (NaSe). Significant higher concentrations were observed after exposure to organic compared to inorganic selenium after oral as well as ip administration. Highest concentrations in both experiments were observed in cerebellum followed by the nearly identical levels in the cerebral hemisphere and spinal cord independent of the chemical form of selenium or the route of administration. The difference in concentrations observed between the different parts of the CNS investigated in each group were, however, not significant. Retention of selenium in the CNS was investigated after a single ip injection (1.7 mg Se/kg body wt) of 75-Se SeMeth or NaSe. In both groups, we observed an initial fast excretion phase followed by a slower excretion phase resembling a first-order reaction. Organic selenium disappeared much slower from all parts of the central nervous system compared to NaSe after a single injection."} {"id": "PMID:1280979", "title": "Selenite-induced inhibition of colony formation by buthionine sulfoximine-sensitive and resistant cell lines.", "content": "We previously demonstrated that treatment of HeLa cells with buthionine sulfoximine (BSO), which decreases the level of cellular glutathione, resulted in a decrease in the potency of selenite in inhibiting cell colony formation. We have now examined the effect of selenite on normal human lung fibroblast (CCL-210) cells, which resemble HeLa cells in their sensitivity to BSO, and on human lung adenocarcinoma (A549) cells, which are relatively insensitive to BSO. We have found that BSO treatment caused an approximately fourfold decrease in selenite potency in the CCL-210 cells, but had no significant effect on its potency in A549 cells. These results support the hypothesis that for selenite to exert its cytotoxic effect, it must undergo the reaction with an SH compound to form the selenotrisulfide. As a result of the lower sensitivity of the tumor cells to BSO, it was possible to achieve a large differential sensitivity to the cytotoxic effect of selenite.", "contents": "Selenite-induced inhibition of colony formation by buthionine sulfoximine-sensitive and resistant cell lines. We previously demonstrated that treatment of HeLa cells with buthionine sulfoximine (BSO), which decreases the level of cellular glutathione, resulted in a decrease in the potency of selenite in inhibiting cell colony formation. We have now examined the effect of selenite on normal human lung fibroblast (CCL-210) cells, which resemble HeLa cells in their sensitivity to BSO, and on human lung adenocarcinoma (A549) cells, which are relatively insensitive to BSO. We have found that BSO treatment caused an approximately fourfold decrease in selenite potency in the CCL-210 cells, but had no significant effect on its potency in A549 cells. These results support the hypothesis that for selenite to exert its cytotoxic effect, it must undergo the reaction with an SH compound to form the selenotrisulfide. As a result of the lower sensitivity of the tumor cells to BSO, it was possible to achieve a large differential sensitivity to the cytotoxic effect of selenite."} {"id": "PMID:1280980", "title": "Zinc uptake by blood cells of rats in zinc deficiency and inflammation.", "content": "In zinc deficiency, the function of leukocytes is impaired. However, the results of studies on the zinc concentration of blood cells in zinc deficiency are conflicting, probably in part because of technical and analytical problems. The aim of this study was to investigate, under standard conditions, the uptake of 65Zn-labeled zinc by blood cells, taken from zinc-deficient rats and from rats in which an inflammation is induced. In both conditions, the serum zinc concentration is reduced. In clinical practice, this makes it difficult to determine whether the decrease in serum zinc is the result of a real or an apparent zinc deficiency. In stress, like an inflammatory disease, the decrease of zinc reflects an apparent zinc deficiency because of redistribution of serum zinc into the liver and because of decrease in serum albumin concentration. Over 70% of the serum zinc is bound to albumin. Blood cells from zinc-deficient and control rats were isolated using a discontinuous Percoll gradient and incubated under nearly physiological conditions in a 65Zn-containing medium. A significant increase in the in vitro uptake of 65Zn-labeled zinc by the blood cells of zinc-deficient rats was seen: erythrocytes 1.3, mononuclear cells 2.0, and polymorphonuclear cells 2.6 times the control values. During inflammation, no change in 65Zn-labeled zinc uptake by erythrocytes and mononuclear cells was demonstrated after 2 d, although the serum zinc and albumin concentrations were decreased, but a small but significant increase in zinc uptake by polymorphonuclear cells was observed. This study of 65Zn uptake in vitro under standard conditions may prove of value for distinguishing in patients real zinc deficiency from apparent zinc deficiency owing to, e.g., stress, although additional experiments should be performed.", "contents": "Zinc uptake by blood cells of rats in zinc deficiency and inflammation. In zinc deficiency, the function of leukocytes is impaired. However, the results of studies on the zinc concentration of blood cells in zinc deficiency are conflicting, probably in part because of technical and analytical problems. The aim of this study was to investigate, under standard conditions, the uptake of 65Zn-labeled zinc by blood cells, taken from zinc-deficient rats and from rats in which an inflammation is induced. In both conditions, the serum zinc concentration is reduced. In clinical practice, this makes it difficult to determine whether the decrease in serum zinc is the result of a real or an apparent zinc deficiency. In stress, like an inflammatory disease, the decrease of zinc reflects an apparent zinc deficiency because of redistribution of serum zinc into the liver and because of decrease in serum albumin concentration. Over 70% of the serum zinc is bound to albumin. Blood cells from zinc-deficient and control rats were isolated using a discontinuous Percoll gradient and incubated under nearly physiological conditions in a 65Zn-containing medium. A significant increase in the in vitro uptake of 65Zn-labeled zinc by the blood cells of zinc-deficient rats was seen: erythrocytes 1.3, mononuclear cells 2.0, and polymorphonuclear cells 2.6 times the control values. During inflammation, no change in 65Zn-labeled zinc uptake by erythrocytes and mononuclear cells was demonstrated after 2 d, although the serum zinc and albumin concentrations were decreased, but a small but significant increase in zinc uptake by polymorphonuclear cells was observed. This study of 65Zn uptake in vitro under standard conditions may prove of value for distinguishing in patients real zinc deficiency from apparent zinc deficiency owing to, e.g., stress, although additional experiments should be performed."} {"id": "PMID:1280981", "title": "Development and application of an alpha-face-specific radioimmunoassay for vitamin B12.", "content": "The first development of an alpha-face-specific radioimmunoassay for vitamin B12 is described. Sheep, fed a cobalt-deficient diet, and immunized with a conjugate between Co-beta carboxypropyl cobalamin and keyhole limpet hemocyanin, were used to produce antisera. The antisera crossreacted with Co-beta derivatives of vitamin B12, but did not crossreact with the alpha-face vitamin B12 analog cobinamide. The antisera were used to develop a sensitive and reproducible radioimmunoassay that was free from contamination with the nonspecific vitamin B12 binding protein, R-protein. Both the radioimmunoassay and measurements of plasma concentrations of methylmalonic acid were applied to the diagnosis of cobalt/vitamin B12 deficiency in sheep. The assay correlated well with a commercially available radioassay and did not falsely detect normal vitamin B12 concentration in plasma samples containing elevated concentrations of methylmalonic acid.", "contents": "Development and application of an alpha-face-specific radioimmunoassay for vitamin B12. The first development of an alpha-face-specific radioimmunoassay for vitamin B12 is described. Sheep, fed a cobalt-deficient diet, and immunized with a conjugate between Co-beta carboxypropyl cobalamin and keyhole limpet hemocyanin, were used to produce antisera. The antisera crossreacted with Co-beta derivatives of vitamin B12, but did not crossreact with the alpha-face vitamin B12 analog cobinamide. The antisera were used to develop a sensitive and reproducible radioimmunoassay that was free from contamination with the nonspecific vitamin B12 binding protein, R-protein. Both the radioimmunoassay and measurements of plasma concentrations of methylmalonic acid were applied to the diagnosis of cobalt/vitamin B12 deficiency in sheep. The assay correlated well with a commercially available radioassay and did not falsely detect normal vitamin B12 concentration in plasma samples containing elevated concentrations of methylmalonic acid."} {"id": "PMID:1280982", "title": "Effect of calcium, copper, and zinc levels in a rapeseed meal diet on mineral and trace element utilization in the rat.", "content": "Mineral and trace element interactions were studied in a balance trial with rats. Calcium, copper, and zinc were supplied to a rapeseed meal diet in a factorial design. Animals were fed ad libitum, and absorption, excretion, and retention of the elements were evaluated either as fractions of total intake or in relation to nitrogen retention to account for differences in food intake and lean body mass increment. The intrinsic content of minerals and trace elements was sufficient to support growth at a rate that could be expected from the rapeseed protein quality. However, when calcium was included in the diet, the intrinsic dietary level of zinc appeared to be limiting, despite the fact that the zinc level was twice the recommended level. Additional zinc supply reversed growth impairment. This calcium-zinc interaction is believed to be owing to the formation of phytate complexes. Calcium addition influenced the calcium, phosphorus, magnesium, zinc, and iron--but not the copper--balances. The addition of calcium reduced the availability of the intrinsic zinc, whereas no effect was seen in the zinc-fortified groups. The availability of intrinsic copper was in a similar way significantly impaired by addition of dietary zinc, whereas copper-supplied groups were unaffected by zinc addition. Intrinsic iron availability was also dependent upon zinc addition, although in a more ambiguous way. Thus, addition of extrinsic minerals to a diet high in phytate can result in significant impairments of growth and mineral utilization.", "contents": "Effect of calcium, copper, and zinc levels in a rapeseed meal diet on mineral and trace element utilization in the rat. Mineral and trace element interactions were studied in a balance trial with rats. Calcium, copper, and zinc were supplied to a rapeseed meal diet in a factorial design. Animals were fed ad libitum, and absorption, excretion, and retention of the elements were evaluated either as fractions of total intake or in relation to nitrogen retention to account for differences in food intake and lean body mass increment. The intrinsic content of minerals and trace elements was sufficient to support growth at a rate that could be expected from the rapeseed protein quality. However, when calcium was included in the diet, the intrinsic dietary level of zinc appeared to be limiting, despite the fact that the zinc level was twice the recommended level. Additional zinc supply reversed growth impairment. This calcium-zinc interaction is believed to be owing to the formation of phytate complexes. Calcium addition influenced the calcium, phosphorus, magnesium, zinc, and iron--but not the copper--balances. The addition of calcium reduced the availability of the intrinsic zinc, whereas no effect was seen in the zinc-fortified groups. The availability of intrinsic copper was in a similar way significantly impaired by addition of dietary zinc, whereas copper-supplied groups were unaffected by zinc addition. Intrinsic iron availability was also dependent upon zinc addition, although in a more ambiguous way. Thus, addition of extrinsic minerals to a diet high in phytate can result in significant impairments of growth and mineral utilization."} {"id": "PMID:1280983", "title": "Tissues and organs as indicators of intestinal absorption of minerals and trace elements, evaluated in rats.", "content": "Tissue and organ deposition and blood parameters were evaluated as indices of mineral and trace element absorption in rats. The absorption of elements was quantified in relation to nitrogen retention, i.e., considering the weight gain and new tissue synthesis. A rapeseed meal diet was supplied with three levels of calcium, two levels of zinc, and two levels of copper in a factorial design. In general, an increase in dietary mineral content increased the relative absorption, which in turn, increased the tissue deposition progressively. Striated muscle, however, did not respond to either an increased calcium or zinc supply. Furthermore, an increased calcium absorption caused a depression of the fractional phosphorus and magnesium content of femur bones. The copper content of the kidneys and the heart muscle was directly proportional to the amount of absorbed zinc and iron, respectively. The iron content of tissue was, in general, inversely proportional to zinc absorption and showed a tendency to be directly proportional to copper absorption. The zinc level in tissues was, in a similar way, inversely correlated to measured calcium absorption. In conclusion, interactions between elements do not only affect the intestinal element absorption, but also the distribution of already absorbed elements in tissues and organs.", "contents": "Tissues and organs as indicators of intestinal absorption of minerals and trace elements, evaluated in rats. Tissue and organ deposition and blood parameters were evaluated as indices of mineral and trace element absorption in rats. The absorption of elements was quantified in relation to nitrogen retention, i.e., considering the weight gain and new tissue synthesis. A rapeseed meal diet was supplied with three levels of calcium, two levels of zinc, and two levels of copper in a factorial design. In general, an increase in dietary mineral content increased the relative absorption, which in turn, increased the tissue deposition progressively. Striated muscle, however, did not respond to either an increased calcium or zinc supply. Furthermore, an increased calcium absorption caused a depression of the fractional phosphorus and magnesium content of femur bones. The copper content of the kidneys and the heart muscle was directly proportional to the amount of absorbed zinc and iron, respectively. The iron content of tissue was, in general, inversely proportional to zinc absorption and showed a tendency to be directly proportional to copper absorption. The zinc level in tissues was, in a similar way, inversely correlated to measured calcium absorption. In conclusion, interactions between elements do not only affect the intestinal element absorption, but also the distribution of already absorbed elements in tissues and organs."} {"id": "PMID:1280984", "title": "Effects of cadmium and copper on zinc transport kinetics by isolated renal proximal cells.", "content": "Zinc, cadmium, and copper are known to interact in many transport processes, but the mechanism of inhibition is widely debated, being either competitive or noncompetitive according to the experimental model employed. We investigated the mechanisms of inhibition of zinc transport by cadmium and copper using renal proximal cells isolated from rabbit kidney. Initial rates of 65Zn uptake were assessed after 0.5 min of incubation. The kinetics parameters of zinc uptake obtained at 20 degrees C were a Jmax of 208.0 +/- 8.4 pmol.min-1.(mg protein)-1, a Km of 15.0 +/- 1.5 microM and an unsaturable constant of 0.259 +/- 0.104 (n = 8). Cadmium at 15 microM competitively inhibited zinc uptake. In the presence of 50 microM cadmium, or copper at both 15 and 50 microM, there was evidence of noncompetitive inhibition. These data suggest that zinc and cadmium enter renal proximal cells via a common, saturable, carrier-mediated process. The mechanisms of the noncompetitive inhibition observed at higher concentrations of cadmium or with copper require further investigation, but may involve a toxic effect on the cytoskeleton.", "contents": "Effects of cadmium and copper on zinc transport kinetics by isolated renal proximal cells. Zinc, cadmium, and copper are known to interact in many transport processes, but the mechanism of inhibition is widely debated, being either competitive or noncompetitive according to the experimental model employed. We investigated the mechanisms of inhibition of zinc transport by cadmium and copper using renal proximal cells isolated from rabbit kidney. Initial rates of 65Zn uptake were assessed after 0.5 min of incubation. The kinetics parameters of zinc uptake obtained at 20 degrees C were a Jmax of 208.0 +/- 8.4 pmol.min-1.(mg protein)-1, a Km of 15.0 +/- 1.5 microM and an unsaturable constant of 0.259 +/- 0.104 (n = 8). Cadmium at 15 microM competitively inhibited zinc uptake. In the presence of 50 microM cadmium, or copper at both 15 and 50 microM, there was evidence of noncompetitive inhibition. These data suggest that zinc and cadmium enter renal proximal cells via a common, saturable, carrier-mediated process. The mechanisms of the noncompetitive inhibition observed at higher concentrations of cadmium or with copper require further investigation, but may involve a toxic effect on the cytoskeleton."} {"id": "PMID:1280985", "title": "New concepts in respiratory chain diseases.", "content": "Recent advances in mitochondrial cytopathies are reviewed. Particular emphasis is given to diseases related to mitochondrial DNA mutations, a field now encompassing myopathic and encephalopathic syndromes, some more common degenerative disorders, and certain aspects of the aging process. Diseases caused by defective oxidative energy generation now have an important place in human pathology.", "contents": "New concepts in respiratory chain diseases. Recent advances in mitochondrial cytopathies are reviewed. Particular emphasis is given to diseases related to mitochondrial DNA mutations, a field now encompassing myopathic and encephalopathic syndromes, some more common degenerative disorders, and certain aspects of the aging process. Diseases caused by defective oxidative energy generation now have an important place in human pathology."} {"id": "PMID:1280986", "title": "Direct application to dairy foods of a Listeria-specific oligonucleotide probe to 16S rRNA.", "content": "A potentially Listeria-specific 28 base oligonucleotide probe was designed from 16S rRNA sequence data. Using either 32P or non-radioactive (alkaline phosphatase) labels, the probe was shown to be highly specific as it hybridised to RNA extracted from all of the species of Listeria but not to any of the other bacteria tested. Both probe methods were highly sensitive and ca 10(2) cfu/ml Listeria could be detected in pure cultures. A rapid procedure for extracting RNA from milk, Camembert and cottage cheese was developed. This allowed the direct application of the probe to these foods and gave a rapid and specific method of detecting > 10(2) cfu/g or ml Listeria in these foods.", "contents": "Direct application to dairy foods of a Listeria-specific oligonucleotide probe to 16S rRNA. A potentially Listeria-specific 28 base oligonucleotide probe was designed from 16S rRNA sequence data. Using either 32P or non-radioactive (alkaline phosphatase) labels, the probe was shown to be highly specific as it hybridised to RNA extracted from all of the species of Listeria but not to any of the other bacteria tested. Both probe methods were highly sensitive and ca 10(2) cfu/ml Listeria could be detected in pure cultures. A rapid procedure for extracting RNA from milk, Camembert and cottage cheese was developed. This allowed the direct application of the probe to these foods and gave a rapid and specific method of detecting > 10(2) cfu/g or ml Listeria in these foods."} {"id": "PMID:1280987", "title": "Interferon treatment for hepatitis B-associated membranous glomerulonephritis in two Chinese children.", "content": "Two Chinese boys, aged 3.5 and 5 years, developed nephrotic syndrome and were chronic carriers of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg). Renal biopsy showed membranous glomerulonephritis and liver biopsy showed chronic persistent hepatitis. They were given interferon-alpha-2a at a dose of 5 MU/m2 on alternate days for 12 and 16 weeks after 2 years of persistent nephrotic syndrome. Patient 1 showed complete remission and resolution of hepatosplenomegaly, but his serum remained positive for HBsAg, HBeAg and hepatitis B virus DNA. Patient 2 showed only a transient clinical response and seroconversion from HBeAg to anti-HBe status. Although not always successful, interferon treatment should be considered in severe persistent nephrotic states, since there is at present no satisfactory treatment for this form of glomerulonephropathy.", "contents": "Interferon treatment for hepatitis B-associated membranous glomerulonephritis in two Chinese children. Two Chinese boys, aged 3.5 and 5 years, developed nephrotic syndrome and were chronic carriers of hepatitis B virus surface antigen (HBsAg) and hepatitis B virus e antigen (HBeAg). Renal biopsy showed membranous glomerulonephritis and liver biopsy showed chronic persistent hepatitis. They were given interferon-alpha-2a at a dose of 5 MU/m2 on alternate days for 12 and 16 weeks after 2 years of persistent nephrotic syndrome. Patient 1 showed complete remission and resolution of hepatosplenomegaly, but his serum remained positive for HBsAg, HBeAg and hepatitis B virus DNA. Patient 2 showed only a transient clinical response and seroconversion from HBeAg to anti-HBe status. Although not always successful, interferon treatment should be considered in severe persistent nephrotic states, since there is at present no satisfactory treatment for this form of glomerulonephropathy."} {"id": "PMID:1280988", "title": "Insulin-like growth factor-1, growth hormone-dependent insulin-like growth factor-binding protein and growth in children with chronic renal failure.", "content": "Insulin-like growth factor-binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) levels were measured by specific radioimmunoassays in children with all degrees of chronic renal failure (CRF). Study group 1 comprised 29 children (10 on dialysis) who had been studied one to four times over 2 years to determine whether IGF-1 and IGFBP-3 levels differed from those in age-matched healthy children and to examine the relationship between these levels and heights. IGF-1 and IGFBP-3 levels did not differ from those in normal children. IGF-1 and IGFBP-3 were significantly correlated, increased with pubertal stage in all children and with age in non-dialysis patients. IGF-1, but not IGFBP-3, correlated with age in dialysis patients. There was no correlation between IGF-1 or IGFBP-3 levels (corrected for age) and height standard deviation score (SDS) in either non-dialysis or dialysis patients. Study group 2 comprised 19 children (7 on dialysis) who were studied prospectively for 1-2 years to examine the relationship between IGF-1 and IGFBP-3 levels, growth rates and nutritional parameters. Mean values of IGF-1 and IGFBP-3 (corrected for age) did not change over 1-year periods, while height SDS fell by -0.38 +/- 0.21 SD/year in dialysis patients and by -0.11 +/- 0.29 SD/year in non-dialysis patients. No significant correlations were found between IGF-1 or IGFBP-3 levels and growth rates or nutritional parameters. Thus growth retardation in children with CRF is not related to circulating levels of IGF-1 or IGFBP-3.", "contents": "Insulin-like growth factor-1, growth hormone-dependent insulin-like growth factor-binding protein and growth in children with chronic renal failure. Insulin-like growth factor-binding protein-3 (IGFBP-3) and insulin-like growth factor-1 (IGF-1) levels were measured by specific radioimmunoassays in children with all degrees of chronic renal failure (CRF). Study group 1 comprised 29 children (10 on dialysis) who had been studied one to four times over 2 years to determine whether IGF-1 and IGFBP-3 levels differed from those in age-matched healthy children and to examine the relationship between these levels and heights. IGF-1 and IGFBP-3 levels did not differ from those in normal children. IGF-1 and IGFBP-3 were significantly correlated, increased with pubertal stage in all children and with age in non-dialysis patients. IGF-1, but not IGFBP-3, correlated with age in dialysis patients. There was no correlation between IGF-1 or IGFBP-3 levels (corrected for age) and height standard deviation score (SDS) in either non-dialysis or dialysis patients. Study group 2 comprised 19 children (7 on dialysis) who were studied prospectively for 1-2 years to examine the relationship between IGF-1 and IGFBP-3 levels, growth rates and nutritional parameters. Mean values of IGF-1 and IGFBP-3 (corrected for age) did not change over 1-year periods, while height SDS fell by -0.38 +/- 0.21 SD/year in dialysis patients and by -0.11 +/- 0.29 SD/year in non-dialysis patients. No significant correlations were found between IGF-1 or IGFBP-3 levels and growth rates or nutritional parameters. Thus growth retardation in children with CRF is not related to circulating levels of IGF-1 or IGFBP-3."} {"id": "PMID:1280989", "title": "Short-term dietary copper deficiency does not inhibit angiogenesis in tumours implanted in striated muscle.", "content": "The effect of dietary copper deficiency on tumour growth, neovascularisation and microvascular integrity was studied in the rat cremaster muscle. Male, weanling Sprague-Dawley rats were fed purified diets which were copper deficient (< 0.5 micrograms g-1 of diet) or copper adequate (5 micrograms g-1 of diet). Seven days after initiation of diets, a chondrosarcoma was implanted in the cremaster muscle of each rat. Five, 10 or 20 days after tumour implantation, rats were anesthetised and their cremasters prepared for observation by intravital microscopy. Intraarterial injection of fluorescein isothiocyanate-conjugated albumin and subsequent observation of fluorescence in the perivascular space indicated no difference in microvascular albumin leakage between the tumour vasculature of copper deficient and copper adequate rats. Neither tumour growth (assessed by wet weight), vascular density (assessed by light microscopy), nor any ultrastructural characteristics of the tumour or its vasculature (assessed by electron microscopy) were affected by copper deficiency. In view of findings by others which indicate changes in tumour characteristics with copper deficiency, we conclude that the copper dependency of tumour growth and vascularisation is a function of the type of tumour, the host tissue, or the conditions of copper depletion.", "contents": "Short-term dietary copper deficiency does not inhibit angiogenesis in tumours implanted in striated muscle. The effect of dietary copper deficiency on tumour growth, neovascularisation and microvascular integrity was studied in the rat cremaster muscle. Male, weanling Sprague-Dawley rats were fed purified diets which were copper deficient (< 0.5 micrograms g-1 of diet) or copper adequate (5 micrograms g-1 of diet). Seven days after initiation of diets, a chondrosarcoma was implanted in the cremaster muscle of each rat. Five, 10 or 20 days after tumour implantation, rats were anesthetised and their cremasters prepared for observation by intravital microscopy. Intraarterial injection of fluorescein isothiocyanate-conjugated albumin and subsequent observation of fluorescence in the perivascular space indicated no difference in microvascular albumin leakage between the tumour vasculature of copper deficient and copper adequate rats. Neither tumour growth (assessed by wet weight), vascular density (assessed by light microscopy), nor any ultrastructural characteristics of the tumour or its vasculature (assessed by electron microscopy) were affected by copper deficiency. In view of findings by others which indicate changes in tumour characteristics with copper deficiency, we conclude that the copper dependency of tumour growth and vascularisation is a function of the type of tumour, the host tissue, or the conditions of copper depletion."} {"id": "PMID:1280990", "title": "Nitroimidazole adducts as markers for tissue hypoxia: mechanistic studies in aerobic normal tissues and tumour cells.", "content": "Two aspects of the aerobic metabolism of nitroimidazole markers for hypoxia were investigated. Several normal murine tissues which are likely to be well oxygenated bind misonidazole at rates comparable to those of hypoxic regions in tumours. The possibility that this aerobic activation occurs via an oxygen independent process such as an initial two electron reduction was studied. Binding to the oesophageal mucosa of mice which occurred under hypoxia in vitro was inhibited by at least 95% in the presence of 10% oxygen. Dicoumarol, an inhibitor of DT-diaphorase, was shown to cause only small reductions in misonidazole binding to oesophageal epithelium and smooth muscle in vitro and to EMT6 tumours, liver, oesophageal and tracheal epithelium, parotid gland and smooth muscle in vivo. Thus an oxygen-insensitive process is not a major cause of the high binding rate in oesophageal mucosa, and may not contribute significantly to the observed binding in other normal tissues. It has been suggested that metabolism of nitroimidazoles by aerobic cells in tumours might be sufficient to minimise access of these compounds to hypoxic regions, particularly at the micromolar concentrations currently in use clinically. The uptake of 125I-iodoazomycin arabinoside by RIF-1 and EMT6 tumours was found to be directly proportional to injected dose over concentrations between 0.5 and 50 microM. Labelling of hypoxic regions in EMT6 tumours by high specific activity 3H-misonidazole at 1 microM was found to be similar to that obtained at 50 microM.", "contents": "Nitroimidazole adducts as markers for tissue hypoxia: mechanistic studies in aerobic normal tissues and tumour cells. Two aspects of the aerobic metabolism of nitroimidazole markers for hypoxia were investigated. Several normal murine tissues which are likely to be well oxygenated bind misonidazole at rates comparable to those of hypoxic regions in tumours. The possibility that this aerobic activation occurs via an oxygen independent process such as an initial two electron reduction was studied. Binding to the oesophageal mucosa of mice which occurred under hypoxia in vitro was inhibited by at least 95% in the presence of 10% oxygen. Dicoumarol, an inhibitor of DT-diaphorase, was shown to cause only small reductions in misonidazole binding to oesophageal epithelium and smooth muscle in vitro and to EMT6 tumours, liver, oesophageal and tracheal epithelium, parotid gland and smooth muscle in vivo. Thus an oxygen-insensitive process is not a major cause of the high binding rate in oesophageal mucosa, and may not contribute significantly to the observed binding in other normal tissues. It has been suggested that metabolism of nitroimidazoles by aerobic cells in tumours might be sufficient to minimise access of these compounds to hypoxic regions, particularly at the micromolar concentrations currently in use clinically. The uptake of 125I-iodoazomycin arabinoside by RIF-1 and EMT6 tumours was found to be directly proportional to injected dose over concentrations between 0.5 and 50 microM. Labelling of hypoxic regions in EMT6 tumours by high specific activity 3H-misonidazole at 1 microM was found to be similar to that obtained at 50 microM."} {"id": "PMID:1280991", "title": "Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia.", "content": "There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen for the expression of BMPs one to six in the prostatic tissue of patients with benign prostatic hyperplasia (BPH), non-metastatic prostatic adenocarcinoma and metastatic prostatic adenocarcinoma. BMPs were expressed in both benign and malignant prostate tissue and in the prostate tumour cell lines, PC3 and DU145. BMPs were also expressed in ocular melanoma tissue, a tissue which rarely metastasizes to bone. BMP-6 expression was detected in the prostate tissue of over 50% of patients with clinically defined metastatic prostate adenocarcinoma, but was not detected in non-metastatic or benign prostate samples or in ocular melanoma tissue. These findings suggest that the BMPs may play a role in the osteoinductive activity of prostate metastases and that the pattern of expression of BMPs may be important in the pathogenesis of osteoblastic metastases associated with prostate adenocarcinoma.", "contents": "Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia. There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen for the expression of BMPs one to six in the prostatic tissue of patients with benign prostatic hyperplasia (BPH), non-metastatic prostatic adenocarcinoma and metastatic prostatic adenocarcinoma. BMPs were expressed in both benign and malignant prostate tissue and in the prostate tumour cell lines, PC3 and DU145. BMPs were also expressed in ocular melanoma tissue, a tissue which rarely metastasizes to bone. BMP-6 expression was detected in the prostate tissue of over 50% of patients with clinically defined metastatic prostate adenocarcinoma, but was not detected in non-metastatic or benign prostate samples or in ocular melanoma tissue. These findings suggest that the BMPs may play a role in the osteoinductive activity of prostate metastases and that the pattern of expression of BMPs may be important in the pathogenesis of osteoblastic metastases associated with prostate adenocarcinoma."} {"id": "PMID:1280992", "title": "Vancomycin: its effect on intracranial pressure.", "content": "Vancomycin is a commonly used antibiotic in neurosurgical practice. It is, however, notorious for causing histamine release which has been associated experimentally with rises in intracranial pressure (ICP). The observation that patients receiving vancomycin had an elevation in ICP during vancomycin infusion over 1 h, and that this elevation persisted for the hour following infusion led to a more formal evaluation. Presented here are data obtained from 6 patients who received vancomycin while on external ventricular drainage for a variety of reasons. The mean ICP for the hour prior to, during and following vancomycin administration was 8 mm Hg (SD 5.6), 13.8 mm Hg (SD 4.9), and 12.6 mm Hg (SD 4.3), respectively. The data were analyzed using a repeated measures analysis of variance between the preadministration values, during-administration values and postadministration values. The p value was significant at < 0.0001. These observations led to experimentation in animals to further assess the effects of vancomycin on ICP. The mean ICP prior to, during and following vancomycin infusion was 1.95 mm Hg (SD 0.75), 8.4 mm Hg (SD 5.1) and 5.6 mm Hg (SD 2.5), respectively. The data were analyzed using a repeated measure analysis of variance for the preadministration, during-administration and postadministration values. The p value was significant at < 0.0001. Based on these data the use of vancomycin should be tempered in the setting of intracranial pathology.", "contents": "Vancomycin: its effect on intracranial pressure. Vancomycin is a commonly used antibiotic in neurosurgical practice. It is, however, notorious for causing histamine release which has been associated experimentally with rises in intracranial pressure (ICP). The observation that patients receiving vancomycin had an elevation in ICP during vancomycin infusion over 1 h, and that this elevation persisted for the hour following infusion led to a more formal evaluation. Presented here are data obtained from 6 patients who received vancomycin while on external ventricular drainage for a variety of reasons. The mean ICP for the hour prior to, during and following vancomycin administration was 8 mm Hg (SD 5.6), 13.8 mm Hg (SD 4.9), and 12.6 mm Hg (SD 4.3), respectively. The data were analyzed using a repeated measures analysis of variance between the preadministration values, during-administration values and postadministration values. The p value was significant at < 0.0001. These observations led to experimentation in animals to further assess the effects of vancomycin on ICP. The mean ICP prior to, during and following vancomycin infusion was 1.95 mm Hg (SD 0.75), 8.4 mm Hg (SD 5.1) and 5.6 mm Hg (SD 2.5), respectively. The data were analyzed using a repeated measure analysis of variance for the preadministration, during-administration and postadministration values. The p value was significant at < 0.0001. Based on these data the use of vancomycin should be tempered in the setting of intracranial pathology."} {"id": "PMID:1280993", "title": "Comparison of three different methods for automated classification of cervical cells.", "content": "Over 4600 exfoliated squamous cervical cells taken from appropriate Papanicolaou samples were classified as normal, mildly dysplastic, moderately dysplastic and severely dysplastic by an experienced cytopathologist. The slides were de-stained and subsequently re-stained with Feulgen Thionin-SO2 stain. Images of the nuclei were then captured, recorded and processed employing an image cytometry device. Automated classification of the cells was carried out using three different methods--discriminant function analysis, a decision tree classifier and a neutral network classifier. The discriminant function analysis method, which combined all dysplastic cells into an abnormal group, achieved a combined error rate of less than 0.4% for moderate and severe dysplastic cells, and less than 40% for mildly dysplastic cells. All three methods yielded comparable results, which approached those of human performance.", "contents": "Comparison of three different methods for automated classification of cervical cells. Over 4600 exfoliated squamous cervical cells taken from appropriate Papanicolaou samples were classified as normal, mildly dysplastic, moderately dysplastic and severely dysplastic by an experienced cytopathologist. The slides were de-stained and subsequently re-stained with Feulgen Thionin-SO2 stain. Images of the nuclei were then captured, recorded and processed employing an image cytometry device. Automated classification of the cells was carried out using three different methods--discriminant function analysis, a decision tree classifier and a neutral network classifier. The discriminant function analysis method, which combined all dysplastic cells into an abnormal group, achieved a combined error rate of less than 0.4% for moderate and severe dysplastic cells, and less than 40% for mildly dysplastic cells. All three methods yielded comparable results, which approached those of human performance."} {"id": "PMID:1280994", "title": "Interaction between the two conserved single-stranded regions at the decoding site of small subunit ribosomal RNA is essential for ribosome function.", "content": "Formation of the tertiary base pair G1401:C1501, which brings together two universally present and highly sequence-conserved single-stranded segments of small subunit ribosomal RNA, is essential for ribosome function. It was previously reported that mutation of G1401 inactivated all in vitro functions of the ribosome [Cunningham et al. (1992) Biochemistry 31, 7629-7637]. Here we show that mutation of C1501 to G was equally inactivating but that the double mutant C1401:G1501 with the base pair reversed had virtually full activity for tRNA binding to the P, A, and I sites and for peptide bond formation. Initiation-dependent formation of the first peptide bond remained 70-85% inhibited, despite full 70S initiation complex formation ability as evidenced by the ability to form fMET-puromycin. These results suggest that the defect in formation of the first peptide bond lies in filling the initial A site, Ai, rather than the subsequent elongation A sites, Ae. An increased mobility around the anticodon was detected by UV cross-linking of the anticodon of P-site-bound tRNA to C1399 as well as to the expected C1400. These findings provide the first experimental evidence for the existence of the G1401:C1501 base pair and show that this base pair, located at the decoding site, is essential for function. The structural implications of tertiary base pair formation are discussed.", "contents": "Interaction between the two conserved single-stranded regions at the decoding site of small subunit ribosomal RNA is essential for ribosome function. Formation of the tertiary base pair G1401:C1501, which brings together two universally present and highly sequence-conserved single-stranded segments of small subunit ribosomal RNA, is essential for ribosome function. It was previously reported that mutation of G1401 inactivated all in vitro functions of the ribosome [Cunningham et al. (1992) Biochemistry 31, 7629-7637]. Here we show that mutation of C1501 to G was equally inactivating but that the double mutant C1401:G1501 with the base pair reversed had virtually full activity for tRNA binding to the P, A, and I sites and for peptide bond formation. Initiation-dependent formation of the first peptide bond remained 70-85% inhibited, despite full 70S initiation complex formation ability as evidenced by the ability to form fMET-puromycin. These results suggest that the defect in formation of the first peptide bond lies in filling the initial A site, Ai, rather than the subsequent elongation A sites, Ae. An increased mobility around the anticodon was detected by UV cross-linking of the anticodon of P-site-bound tRNA to C1399 as well as to the expected C1400. These findings provide the first experimental evidence for the existence of the G1401:C1501 base pair and show that this base pair, located at the decoding site, is essential for function. The structural implications of tertiary base pair formation are discussed."} {"id": "PMID:1280995", "title": "In vivo chemical footprinting of the Escherichia coli ribosome.", "content": "We have studied the in vivo chemical accessibility of 16S rRNA residues A349-G1505 in the small subunit of the Escherichia coli ribosome. Exponentially growing E. coli cultures were reacted with dimethyl sulfate, and the reactive sites on the 16S ribosomal RNA were analyzed by reverse transcription, an assay which detects reactions at N1-A and N3-C. In agreement with previous in vitro results, three regions of 16S RNA appeared particularly reactive to dimethyl sulfate: hairpin 27 (residues A892-A915) of the central domain, and hairpin 33-33A (residues A994-C1037) and the tip of hairpin 41 (residues A1256-A1275), both from the 3' major domain. These three regions contained 52% of the reactive residues but only 8% of the residues scanned. In contrast to previous in vitro results, three small sections of 16S RNA appeared protected: the tip of hairpins 26 (residue A845) and 31 (residues A968-A969), and residues A1418, A1441, and A1483 of the middle body of hairpin 44. Four of the dimethyl sulfate reactive sites (A831, C948, A1019, and C1192) are located in positions usually assumed to be double-stranded (helices 26, 30, 33-33A, and 34), which suggests alternative structures for these helices at least during part of the translation process, as if the residues in question belonged to \"conformational switches.\" The addition of chloramphenicol protected residues A831, A1035-A1036, and A1503, which suggests that they belong to the mobile regions of the elongating ribosome, and become exposed during some transition(s) from one ribosomal state to the other during the elongation cycle.", "contents": "In vivo chemical footprinting of the Escherichia coli ribosome. We have studied the in vivo chemical accessibility of 16S rRNA residues A349-G1505 in the small subunit of the Escherichia coli ribosome. Exponentially growing E. coli cultures were reacted with dimethyl sulfate, and the reactive sites on the 16S ribosomal RNA were analyzed by reverse transcription, an assay which detects reactions at N1-A and N3-C. In agreement with previous in vitro results, three regions of 16S RNA appeared particularly reactive to dimethyl sulfate: hairpin 27 (residues A892-A915) of the central domain, and hairpin 33-33A (residues A994-C1037) and the tip of hairpin 41 (residues A1256-A1275), both from the 3' major domain. These three regions contained 52% of the reactive residues but only 8% of the residues scanned. In contrast to previous in vitro results, three small sections of 16S RNA appeared protected: the tip of hairpins 26 (residue A845) and 31 (residues A968-A969), and residues A1418, A1441, and A1483 of the middle body of hairpin 44. Four of the dimethyl sulfate reactive sites (A831, C948, A1019, and C1192) are located in positions usually assumed to be double-stranded (helices 26, 30, 33-33A, and 34), which suggests alternative structures for these helices at least during part of the translation process, as if the residues in question belonged to \"conformational switches.\" The addition of chloramphenicol protected residues A831, A1035-A1036, and A1503, which suggests that they belong to the mobile regions of the elongating ribosome, and become exposed during some transition(s) from one ribosomal state to the other during the elongation cycle."} {"id": "PMID:1280996", "title": "Kinetics of intermolecular cleavage by hammerhead ribozymes.", "content": "The hammerhead catalytic RNA effects cleavage of the phosphodiester backbone of RNA through a transesterification mechanism that generates products with 2'-3'-cyclic phosphate and 5'-hydroxyl termini. A minimal kinetic mechanism for the intermolecular hammerhead cleavage reaction includes substrate binding, cleavage, and product release. Elemental rate constants for these steps were measured with six hammerhead sequences. Changes in substrate length and sequence had little effect on the rate of the cleavage step, but dramatic differences were observed in the substrate dissociation and product release steps that require helix-coil transitions. Rates of substrate binding and product dissociation correlated well with predictions based on the behavior of simple RNA duplexes, but substrate dissociation rates were significantly faster than expected. Ribozyme and substrate alterations that eliminated catalytic activity increased the stability of the hammerhead complex. These results suggest that substrate destabilization may play a role in hammerhead catalysis.", "contents": "Kinetics of intermolecular cleavage by hammerhead ribozymes. The hammerhead catalytic RNA effects cleavage of the phosphodiester backbone of RNA through a transesterification mechanism that generates products with 2'-3'-cyclic phosphate and 5'-hydroxyl termini. A minimal kinetic mechanism for the intermolecular hammerhead cleavage reaction includes substrate binding, cleavage, and product release. Elemental rate constants for these steps were measured with six hammerhead sequences. Changes in substrate length and sequence had little effect on the rate of the cleavage step, but dramatic differences were observed in the substrate dissociation and product release steps that require helix-coil transitions. Rates of substrate binding and product dissociation correlated well with predictions based on the behavior of simple RNA duplexes, but substrate dissociation rates were significantly faster than expected. Ribozyme and substrate alterations that eliminated catalytic activity increased the stability of the hammerhead complex. These results suggest that substrate destabilization may play a role in hammerhead catalysis."} {"id": "PMID:1280997", "title": "Implication of RNA structure on antisense oligonucleotide hybridization kinetics.", "content": "A 47-nucleotide transcript of the activated Ha-ras gene was prepared and determined, by enzymatic structure mapping, to form a stable hairpin structure. Six antisense decaribonucleotides were designed, and association constants (Ka) for the hairpin- and length-matched complements were measured. Two of the antisense oligonucleotides targeted to the loop had nearly equal affinity for the transcript compared to the complement. The others, including one oligonucleotide complementary to the 3' side of the single-stranded loop, bound 10(5)-10(6)-fold less tightly to the transcript than to the short complement. We propose the difference in affinity is due to the target structure, both the secondary structure of the stem and the structure in the loop. Measurement of the bimolecular association rate constant, k1, and the dissociation rate constant, k-1, for these oligonucleotides indicates the observed relationship between affinity and structure is primarily due to k1.", "contents": "Implication of RNA structure on antisense oligonucleotide hybridization kinetics. A 47-nucleotide transcript of the activated Ha-ras gene was prepared and determined, by enzymatic structure mapping, to form a stable hairpin structure. Six antisense decaribonucleotides were designed, and association constants (Ka) for the hairpin- and length-matched complements were measured. Two of the antisense oligonucleotides targeted to the loop had nearly equal affinity for the transcript compared to the complement. The others, including one oligonucleotide complementary to the 3' side of the single-stranded loop, bound 10(5)-10(6)-fold less tightly to the transcript than to the short complement. We propose the difference in affinity is due to the target structure, both the secondary structure of the stem and the structure in the loop. Measurement of the bimolecular association rate constant, k1, and the dissociation rate constant, k-1, for these oligonucleotides indicates the observed relationship between affinity and structure is primarily due to k1."} {"id": "PMID:1280998", "title": "Constrained and restrained refinement in EXAFS data analysis with curved wave theory.", "content": "This paper describes methods of constrained and restrained refinement of EXAFS data which provide a means of substantially reducing the number of independent parameters compared to conventional least-squares methods commonly used. Constrained refinement allows a major reduction in the number of free parameters for a refinement of a structural model. In restrained refinement, additional structural information from well-characterized small molecules is used to provide additional observations in the data analysis. Even though these methods are of general application to the majority of complex systems, they are particularly valuable for biological molecules. The methods are of major advantage for ligands where significant multiple scattering is present, e.g., histidine, tyrosine, CO, CN, etc. The bases of these methods are described, and applications to some complex chemical and biological systems are given.", "contents": "Constrained and restrained refinement in EXAFS data analysis with curved wave theory. This paper describes methods of constrained and restrained refinement of EXAFS data which provide a means of substantially reducing the number of independent parameters compared to conventional least-squares methods commonly used. Constrained refinement allows a major reduction in the number of free parameters for a refinement of a structural model. In restrained refinement, additional structural information from well-characterized small molecules is used to provide additional observations in the data analysis. Even though these methods are of general application to the majority of complex systems, they are particularly valuable for biological molecules. The methods are of major advantage for ligands where significant multiple scattering is present, e.g., histidine, tyrosine, CO, CN, etc. The bases of these methods are described, and applications to some complex chemical and biological systems are given."} {"id": "PMID:1281000", "title": "Identification of two general diffusion channels in the outer membrane of pea mitochondria.", "content": "Reconstitution experiments were performed on lipid bilayer membranes in the presence of detergent solubilized mitochondrial membranes of pea seedlings (Pisum sativum). The addition of the detergent-solubilized material to the membranes resulted in a strong increase of the membrane conductance. To identify the proteins responsible for membrane activity the detergent extracts were applied to a hydroxyapatite (HTP) column and the fractions were tested for channel formation. The eluate of the column contained a protein which migrated as a single band with an apparent molecular mass of 30 kDa on SDS-PAGE. This channel was identified as the porin of pea mitochondria since it formed voltage-dependent channels with single-channel conductances of 1.5 and 3.7 nS in 1 M KCl and an estimated effective diameter of about 1.7 nm. Further elution of the column with KCl containing solutions yielded fractions which resulted in the formation of transient channels in lipid bilayer membranes. These channels had a single-channel conductance of 2.2 nS in 1 M KCl and had also the characteristics of general diffusion pores with an estimated effective diameter of 1.2 nm. Zero-current membrane potential measurements suggested that pea porin was anion-selective in the open state. The selectivity of the second channel was investigated by the measurement of the reversal potential. It was also slightly anion-selective. Its possible role in the metabolism of mitochondria is discussed.", "contents": "Identification of two general diffusion channels in the outer membrane of pea mitochondria. Reconstitution experiments were performed on lipid bilayer membranes in the presence of detergent solubilized mitochondrial membranes of pea seedlings (Pisum sativum). The addition of the detergent-solubilized material to the membranes resulted in a strong increase of the membrane conductance. To identify the proteins responsible for membrane activity the detergent extracts were applied to a hydroxyapatite (HTP) column and the fractions were tested for channel formation. The eluate of the column contained a protein which migrated as a single band with an apparent molecular mass of 30 kDa on SDS-PAGE. This channel was identified as the porin of pea mitochondria since it formed voltage-dependent channels with single-channel conductances of 1.5 and 3.7 nS in 1 M KCl and an estimated effective diameter of about 1.7 nm. Further elution of the column with KCl containing solutions yielded fractions which resulted in the formation of transient channels in lipid bilayer membranes. These channels had a single-channel conductance of 2.2 nS in 1 M KCl and had also the characteristics of general diffusion pores with an estimated effective diameter of 1.2 nm. Zero-current membrane potential measurements suggested that pea porin was anion-selective in the open state. The selectivity of the second channel was investigated by the measurement of the reversal potential. It was also slightly anion-selective. Its possible role in the metabolism of mitochondria is discussed."} {"id": "PMID:1281001", "title": "Therapeutic agents for treatment of established metastases and inhibitors of metastatic spread: preclinical and clinical progress.", "content": "This article reviews recently described agents for the treatment of established metastases or inhibitors of metastatic spread. Recent progress in both preclinical models of experimental metastasis and clinical evaluation is highlighted. Where possible, distinctions are made between therapeutic agents for established metastatic tumors and those that merely interfere with the process of metastasis. The approaches emphasized include radiotherapy, cytotoxic chemotherapy, targeting the metastatic process and tumor metastases (adhesion, invasion, and angiogenesis), and modulation of the immune response, including chemoimmunotherapy. Emphasis has been placed on the necessity of using appropriate animal models of metastatic disease for the discovery and development of novel and effective antimetastatic therapeutic agents. Also addressed is the likelihood that future approaches to the metastasis problem will employ novel combined antimetastatic therapeutic modalities.", "contents": "Therapeutic agents for treatment of established metastases and inhibitors of metastatic spread: preclinical and clinical progress. This article reviews recently described agents for the treatment of established metastases or inhibitors of metastatic spread. Recent progress in both preclinical models of experimental metastasis and clinical evaluation is highlighted. Where possible, distinctions are made between therapeutic agents for established metastatic tumors and those that merely interfere with the process of metastasis. The approaches emphasized include radiotherapy, cytotoxic chemotherapy, targeting the metastatic process and tumor metastases (adhesion, invasion, and angiogenesis), and modulation of the immune response, including chemoimmunotherapy. Emphasis has been placed on the necessity of using appropriate animal models of metastatic disease for the discovery and development of novel and effective antimetastatic therapeutic agents. Also addressed is the likelihood that future approaches to the metastasis problem will employ novel combined antimetastatic therapeutic modalities."} {"id": "PMID:1280999", "title": "Vascular cell adhesion molecule-1 is induced on endothelium during acute rejection in human cardiac allografts.", "content": "An infiltration of mononuclear leukocytes into the myocardium of a cardiac allograft is diagnostic of transplant rejection. The presence of these leukocytes implies their adhesion to, and subsequent migration through, the vascular endothelium. Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are endothelial proteins that have been shown to be involved in the binding of mononuclear leukocytes to the endothelium in vitro. We investigated the induction of these proteins in a random series from 99 endomyocardial biopsy specimens obtained from 1 week to 4 years after cardiac allograft transplantation. Intercellular adhesion molecule-1 was found to be expressed constitutively by the myocardial microvasculature in the recipient's original heart and in the posttransplantation biopsy specimens. No correlation was found between the presence or absence of intercellular adhesion molecule-1 expression and cellular rejection. In contrast, no endothelial expression of vascular cell adhesion molecule-1 was observed in the recipient heart or in endomyocardial biopsy specimens lacking cellular rejection. The presence of vascular cell adhesion molecule-1 significantly correlated with the presence of mild or moderate rejection. The de novo induction of vascular cell adhesion molecule-1 on the myocardial vasculature during periods of rejection, in addition to the recruitment of mononuclear leukocytes that are known to bind to this protein, suggests that the expression of this endothelial adhesion protein could be of use in diagnosing rejection.", "contents": "Vascular cell adhesion molecule-1 is induced on endothelium during acute rejection in human cardiac allografts. An infiltration of mononuclear leukocytes into the myocardium of a cardiac allograft is diagnostic of transplant rejection. The presence of these leukocytes implies their adhesion to, and subsequent migration through, the vascular endothelium. Intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are endothelial proteins that have been shown to be involved in the binding of mononuclear leukocytes to the endothelium in vitro. We investigated the induction of these proteins in a random series from 99 endomyocardial biopsy specimens obtained from 1 week to 4 years after cardiac allograft transplantation. Intercellular adhesion molecule-1 was found to be expressed constitutively by the myocardial microvasculature in the recipient's original heart and in the posttransplantation biopsy specimens. No correlation was found between the presence or absence of intercellular adhesion molecule-1 expression and cellular rejection. In contrast, no endothelial expression of vascular cell adhesion molecule-1 was observed in the recipient heart or in endomyocardial biopsy specimens lacking cellular rejection. The presence of vascular cell adhesion molecule-1 significantly correlated with the presence of mild or moderate rejection. The de novo induction of vascular cell adhesion molecule-1 on the myocardial vasculature during periods of rejection, in addition to the recruitment of mononuclear leukocytes that are known to bind to this protein, suggests that the expression of this endothelial adhesion protein could be of use in diagnosing rejection."} {"id": "PMID:1281002", "title": "Detection of bluetongue virus serogroup by polymerase chain reaction.", "content": "To facilitate detection of active bluetongue virus (BTV) infection, a polymerase chain reaction (PCR) protocol was developed. The BTV reverse transcriptase PCR (RT-PCR) is a 1-tube reaction and involves chemical denaturation of the double-stranded viral RNA target, a complementary DNA (cDNA) synthesis step, and PCR amplification of the cDNA. BTV RT-PCR using primers derived from highly conserved genome segment 10 results in a 251-base pair (bp) product. BTV RNA from all USA prototype serotypes 2, 10, 11, 13, and 17; a wide spectrum of USA BTV field isolates including serotypes 10, 11, 13, and 17; and a spectrum of Israeli field isolates including serotypes 2, 4, 6, 10, and 16 were detected by BTV RT-PCR. With agarose gels, the 251-bp product was detected from as little as 100 fg-1 pg of BTV RNA, which is equivalent to 5 x 10(3)-5 x 10(4) viral particles or 5 x 10(2)-5 x 10(3) infectious units. With dot blot hybridization, specific PCR product was detected from as little as 1 fg of BTV RNA, which is equivalent to 50 viral particles, or 5 infectious units. This level of sensitivity is comparable to that of virus isolation. The BTV RT-PCR using primers derived from genome segment 10 can detect a wide spectrum of USA and Israeli BTV serotypes and has potential for detection of infection by the BTV serogroup. Application of this BTV PCR to clinical samples is in progress.", "contents": "Detection of bluetongue virus serogroup by polymerase chain reaction. To facilitate detection of active bluetongue virus (BTV) infection, a polymerase chain reaction (PCR) protocol was developed. The BTV reverse transcriptase PCR (RT-PCR) is a 1-tube reaction and involves chemical denaturation of the double-stranded viral RNA target, a complementary DNA (cDNA) synthesis step, and PCR amplification of the cDNA. BTV RT-PCR using primers derived from highly conserved genome segment 10 results in a 251-base pair (bp) product. BTV RNA from all USA prototype serotypes 2, 10, 11, 13, and 17; a wide spectrum of USA BTV field isolates including serotypes 10, 11, 13, and 17; and a spectrum of Israeli field isolates including serotypes 2, 4, 6, 10, and 16 were detected by BTV RT-PCR. With agarose gels, the 251-bp product was detected from as little as 100 fg-1 pg of BTV RNA, which is equivalent to 5 x 10(3)-5 x 10(4) viral particles or 5 x 10(2)-5 x 10(3) infectious units. With dot blot hybridization, specific PCR product was detected from as little as 1 fg of BTV RNA, which is equivalent to 50 viral particles, or 5 infectious units. This level of sensitivity is comparable to that of virus isolation. The BTV RT-PCR using primers derived from genome segment 10 can detect a wide spectrum of USA and Israeli BTV serotypes and has potential for detection of infection by the BTV serogroup. Application of this BTV PCR to clinical samples is in progress."} {"id": "PMID:1281006", "title": "Neural computing in discovering RNA interactions.", "content": "High-order RNA structures are involved in regulating many biological processes; various algorithms have been designed to predict them. Experimental methods to probe such structures and to decipher the results are tedious. Artificial intelligence and the neural network approach can support the process of discovering RNA structures. Secondary structures of RNA molecules are probed by autoradiographing gels, separating end-labeled fragments generated by base-specific RNases. This process is performed in both conditions, denaturing (for sequencing purposes) and native. The resultant autoradiograms are scanned using line-detection techniques to identify the fragments by comparing the lines with those obtained by 'alkaline ladders'. The identified paired bases are treated by either one of two methods to find the foldings which are consistent with the RNases' 'cutting' rules. One exploits the maximum independent set algorithm; the other, the planarization algorithm. They require, respectively, n and n2 processing elements, where n is the number of base pairs. The state of the system usually converges to the near-optimum solution within about 500 iteration steps, where each processing element implements the McCulloch-Pitts binary neuron. Our simulator, based on the proposed algorithm, discovered a new structure in a sequence of 38 bases, which is more stable than that formerly proposed.", "contents": "Neural computing in discovering RNA interactions. High-order RNA structures are involved in regulating many biological processes; various algorithms have been designed to predict them. Experimental methods to probe such structures and to decipher the results are tedious. Artificial intelligence and the neural network approach can support the process of discovering RNA structures. Secondary structures of RNA molecules are probed by autoradiographing gels, separating end-labeled fragments generated by base-specific RNases. This process is performed in both conditions, denaturing (for sequencing purposes) and native. The resultant autoradiograms are scanned using line-detection techniques to identify the fragments by comparing the lines with those obtained by 'alkaline ladders'. The identified paired bases are treated by either one of two methods to find the foldings which are consistent with the RNases' 'cutting' rules. One exploits the maximum independent set algorithm; the other, the planarization algorithm. They require, respectively, n and n2 processing elements, where n is the number of base pairs. The state of the system usually converges to the near-optimum solution within about 500 iteration steps, where each processing element implements the McCulloch-Pitts binary neuron. Our simulator, based on the proposed algorithm, discovered a new structure in a sequence of 38 bases, which is more stable than that formerly proposed."} {"id": "PMID:1281007", "title": "Molecular biology techniques and their applicability to the study of diabetes and hypertension: the renin-angiotensin system as an example.", "content": "Recently developed molecular biology techniques lend themselves to the study of both normal physiology and pathophysiology. This review discusses a number of such techniques and their applicability to the study of diabetes and hypertension with the renin-angiotensin system as an example. The demonstration of specific mRNA in tissue provides strong evidence that the protein for which it encodes is expressed there. The contribution of several methods to demonstrate mRNA expression including Northern analysis, slot blot analysis, solution hybridization, in situ hybridization, run-on assays, and polymerase chain reaction are discussed in the light of how these are used to study renin-angiotensin system mechanisms. Additionally, recent developments in the study of gene transfer and identification of genes are reviewed.", "contents": "Molecular biology techniques and their applicability to the study of diabetes and hypertension: the renin-angiotensin system as an example. Recently developed molecular biology techniques lend themselves to the study of both normal physiology and pathophysiology. This review discusses a number of such techniques and their applicability to the study of diabetes and hypertension with the renin-angiotensin system as an example. The demonstration of specific mRNA in tissue provides strong evidence that the protein for which it encodes is expressed there. The contribution of several methods to demonstrate mRNA expression including Northern analysis, slot blot analysis, solution hybridization, in situ hybridization, run-on assays, and polymerase chain reaction are discussed in the light of how these are used to study renin-angiotensin system mechanisms. Additionally, recent developments in the study of gene transfer and identification of genes are reviewed."} {"id": "PMID:1281008", "title": "Methyl green and its analogues bind selectively to AT-rich regions of native DNA.", "content": "Methyl green has long been used as a DNA stain in histochemistry. The sequence selective binding of the cationic triphenylmethane dyes methyl green, crystal violet and Malachite green to DNA was investigated by DNAase 1 and micrococcal nuclease footprinting. At low concentrations the ligands showed similar footprinting patterns which centred around AT-rich regions with a mild preference for hompolymeric A and T. At higher concentrations the dyes bound to almost all available DNA sites. Models, with and without intercalation are discussed to account for the specific binding.", "contents": "Methyl green and its analogues bind selectively to AT-rich regions of native DNA. Methyl green has long been used as a DNA stain in histochemistry. The sequence selective binding of the cationic triphenylmethane dyes methyl green, crystal violet and Malachite green to DNA was investigated by DNAase 1 and micrococcal nuclease footprinting. At low concentrations the ligands showed similar footprinting patterns which centred around AT-rich regions with a mild preference for hompolymeric A and T. At higher concentrations the dyes bound to almost all available DNA sites. Models, with and without intercalation are discussed to account for the specific binding."} {"id": "PMID:1281009", "title": "Comparative study of in situ hybridization and immunohistochemical techniques for the detection of human papillomavirus in lesions of the uterine cervix.", "content": "Among the techniques currently used for the detection of human papillomavirus (HPV) in genital lesions, only two correlate HPV with the histopathological findings of the lesion: immunohistochemistry and in situ hybridization. Consequently, we were prompted to carry out a comparative study on both techniques to check their utility and efficacy as routine diagnostic methods. 52 biopsy specimens of uterine cervix diagnosed histopathologically as condylomas and cervical intraepithelial neoplasia+koilocytosis were studied by immunohistochemical and in situ hybridization techniques using a polyclonal antibody against the common antigen of the HPV capsid and three biotinylated DNA probes specific to HPV types 6/11, 16/18 and 31/35/51. Immunohistochemistry detected 21 positive cases (40.38%), whereas in situ hybridization detected 40 positive cases (76.92%); of the latter, 30 were positive for HPV types 6/11, 3 for HPV types 16/18 and 11 for HPV types 31/35/51. The results suggest that in situ hybridization is a more sensitive technique than immunohistochemistry. However, we recommend the use of both techniques in the case of potentially malignant lesions since better prognostic information can be obtained from joint analysis of both results.", "contents": "Comparative study of in situ hybridization and immunohistochemical techniques for the detection of human papillomavirus in lesions of the uterine cervix. Among the techniques currently used for the detection of human papillomavirus (HPV) in genital lesions, only two correlate HPV with the histopathological findings of the lesion: immunohistochemistry and in situ hybridization. Consequently, we were prompted to carry out a comparative study on both techniques to check their utility and efficacy as routine diagnostic methods. 52 biopsy specimens of uterine cervix diagnosed histopathologically as condylomas and cervical intraepithelial neoplasia+koilocytosis were studied by immunohistochemical and in situ hybridization techniques using a polyclonal antibody against the common antigen of the HPV capsid and three biotinylated DNA probes specific to HPV types 6/11, 16/18 and 31/35/51. Immunohistochemistry detected 21 positive cases (40.38%), whereas in situ hybridization detected 40 positive cases (76.92%); of the latter, 30 were positive for HPV types 6/11, 3 for HPV types 16/18 and 11 for HPV types 31/35/51. The results suggest that in situ hybridization is a more sensitive technique than immunohistochemistry. However, we recommend the use of both techniques in the case of potentially malignant lesions since better prognostic information can be obtained from joint analysis of both results."} {"id": "PMID:1281010", "title": "HER-2/neu oncogene expression and DNA ploidy in normal human kidney and renal cell carcinoma.", "content": "Using flow cytometry (FCM), we have investigated both the DNA content (stained with propidium iodide) and HER-2/neu oncogene expression (revealed by means of an anti-HER-2/neu monoclonal antibody) in neoplastic and non-neoplastic kidney samples from 20 patients with renal cell carcinoma. All the non-neoplastic samples and 15/20 (75%) renal cell cancers showed diploid modal DNA content while the remaining 5 neoplastic sample (25%) showed both diploid and hyperdiploid cell populations. In normal kidney the level of HER-2/neu oncoprotein was low (median fluorescence values in arbitrary units = 7.5 AU, range: 4-10 AU). In diploid renal cancers the level of HER-2/neu was slightly increased (median fluorescence values = 20 AU, range: 9.5-30 AU) (p < .005). The relationship of HER-2/neu expression to the cell cycle in these tumor samples is not clear since most of the cells express the antigen in all phases of the cell cycle. On the other hand, there is an association between HER-2/neu expression and abnormal DNA content suggesting that aneuploid pattern may be biologically related to overexpression of the HER-2/neu gene.", "contents": "HER-2/neu oncogene expression and DNA ploidy in normal human kidney and renal cell carcinoma. Using flow cytometry (FCM), we have investigated both the DNA content (stained with propidium iodide) and HER-2/neu oncogene expression (revealed by means of an anti-HER-2/neu monoclonal antibody) in neoplastic and non-neoplastic kidney samples from 20 patients with renal cell carcinoma. All the non-neoplastic samples and 15/20 (75%) renal cell cancers showed diploid modal DNA content while the remaining 5 neoplastic sample (25%) showed both diploid and hyperdiploid cell populations. In normal kidney the level of HER-2/neu oncoprotein was low (median fluorescence values in arbitrary units = 7.5 AU, range: 4-10 AU). In diploid renal cancers the level of HER-2/neu was slightly increased (median fluorescence values = 20 AU, range: 9.5-30 AU) (p < .005). The relationship of HER-2/neu expression to the cell cycle in these tumor samples is not clear since most of the cells express the antigen in all phases of the cell cycle. On the other hand, there is an association between HER-2/neu expression and abnormal DNA content suggesting that aneuploid pattern may be biologically related to overexpression of the HER-2/neu gene."} {"id": "PMID:1281011", "title": "Qualitative and quantitative changes in nuclear DNA and phenotypic gene expression in human malignant skin tumors during their progression.", "content": "Qualitative and quantitative changes in nuclear DNA and phenotypic expression of human malignant skin tumors were examined during the course of progression. The numerical abnormalities of chromosomes demonstrated by interphase cytogenetics using the chromosome-specific in situ hybridization technique, were also used to reveal qualitative DNA changes in malignant tumor cells. For the analysis of the quantitative changes in nuclear DNA, fluorescence cytophotometry was used on the DAPI-stained tumor cells isolated from the paraffin-embedded sections. To survey abnormal gene expression in malignant tumor cells, lectin histochemistry for different sugar residues, immunohistochemical staining of HLA-DR, and in situ hybridization for H-ras, c-myc, N-myc or v-fos were used. The results showed that: 1) in one case of squamous cell carcinoma with invasion, the number of chromosomal abnormalities was much greater in the invasive than in non-invasive parts, with marked topographical heterogeneities; 2) the DNA-ploidies were largely shifted to the higher side with aneuploid stem-lines and polyploid cells in the invasive parts of all malignant tumors; 3) the expression of HLA-DR was induced at the invasive fronts of malignant melanomas; 4) the GS-I specific sugar residue(D-galactose) appeared in all extra-mammary Paget's cells; and 5) expression of \"oncogenes\" was found in about 60% of all malignant tumors examined. Thus, the progression of malignancy is accompanied by both qualitative and quantitative changes in nuclear DNA, resulting in abnormal gene expression.", "contents": "Qualitative and quantitative changes in nuclear DNA and phenotypic gene expression in human malignant skin tumors during their progression. Qualitative and quantitative changes in nuclear DNA and phenotypic expression of human malignant skin tumors were examined during the course of progression. The numerical abnormalities of chromosomes demonstrated by interphase cytogenetics using the chromosome-specific in situ hybridization technique, were also used to reveal qualitative DNA changes in malignant tumor cells. For the analysis of the quantitative changes in nuclear DNA, fluorescence cytophotometry was used on the DAPI-stained tumor cells isolated from the paraffin-embedded sections. To survey abnormal gene expression in malignant tumor cells, lectin histochemistry for different sugar residues, immunohistochemical staining of HLA-DR, and in situ hybridization for H-ras, c-myc, N-myc or v-fos were used. The results showed that: 1) in one case of squamous cell carcinoma with invasion, the number of chromosomal abnormalities was much greater in the invasive than in non-invasive parts, with marked topographical heterogeneities; 2) the DNA-ploidies were largely shifted to the higher side with aneuploid stem-lines and polyploid cells in the invasive parts of all malignant tumors; 3) the expression of HLA-DR was induced at the invasive fronts of malignant melanomas; 4) the GS-I specific sugar residue(D-galactose) appeared in all extra-mammary Paget's cells; and 5) expression of \"oncogenes\" was found in about 60% of all malignant tumors examined. Thus, the progression of malignancy is accompanied by both qualitative and quantitative changes in nuclear DNA, resulting in abnormal gene expression."} {"id": "PMID:1281012", "title": "Amplification of GC-rich DNAs in neuronal nuclei of Planorbarius corneus (L.) (Mollusca, pulmonata).", "content": "Quantitative microfluorometric evaluation of DNA content in nerve cells of the Pulmonate Gastropod Planorbarius corneus has indicated that the increase in nuclear volume is due to DNA amplification. Indeed, it has been observed that the DNA contents are scattered at random between 2C and 1,000C values. This is not in agreement with the occurrence of repeated duplications of the whole genome. Furthermore, chromatin photo-oxidation, a technique useful in discriminating GC-rich from AT-rich DNAs, suggests that DNA amplification involves GC-rich sequences.", "contents": "Amplification of GC-rich DNAs in neuronal nuclei of Planorbarius corneus (L.) (Mollusca, pulmonata). Quantitative microfluorometric evaluation of DNA content in nerve cells of the Pulmonate Gastropod Planorbarius corneus has indicated that the increase in nuclear volume is due to DNA amplification. Indeed, it has been observed that the DNA contents are scattered at random between 2C and 1,000C values. This is not in agreement with the occurrence of repeated duplications of the whole genome. Furthermore, chromatin photo-oxidation, a technique useful in discriminating GC-rich from AT-rich DNAs, suggests that DNA amplification involves GC-rich sequences."} {"id": "PMID:1281014", "title": "Effects of sham hemodialysis on plasma levels of vasoactive peptides in patients with uremia.", "content": "Changes in plasma levels of vasoactive peptides during hemodialysis have mainly been attributed to changes in plasma volume and osmolality. This study investigated the effect of the extracorporeal circulation on plasma levels of vasoactive peptides, noradrenaline, and renin. Eleven stable hemodialysis patients were studied during sham dialysis for 60 min using a Cuprophan dialyzer (Alwall GFE11, Gambro AB, Lund, Sweden). With regard to vasoconstrictors, there was an increase in noradrenaline (NA) (13%, p < 0.05) and renin (PRA) (32%, p < 0.05), while arginine vasopressin and neuropeptide Y remained unaltered. Concerning vasodilators, an increase in substance P (SP) (23%, p < 0.05) and vasoactive intestinal peptide (VIP) (15%, p < 0.01) was observed, while a decrease in atrial natriuretic peptide (ANP) (17%, p < 0.05) and motilin (MOT) (24%, p < 0.01) occurred. Calcitonin gene related peptide and beta endorphin were unaltered. A decrease in blood pressure was observed, while heart rate remained unchanged. The authors conclude that the extracorporeal circulation, per se, affects plasma levels of vasoactive substances and influences vascular stability. The decrease in ANP and MOT might be due to adsorption to the dialysis membrane. The increase in some vasoconstrictors (NA, PRA) and vasodilators (SP, VIP) might be induced by the blood-artificial surface contact, or by other factors, e.g., heparin or cooling of the blood during the procedure.", "contents": "Effects of sham hemodialysis on plasma levels of vasoactive peptides in patients with uremia. Changes in plasma levels of vasoactive peptides during hemodialysis have mainly been attributed to changes in plasma volume and osmolality. This study investigated the effect of the extracorporeal circulation on plasma levels of vasoactive peptides, noradrenaline, and renin. Eleven stable hemodialysis patients were studied during sham dialysis for 60 min using a Cuprophan dialyzer (Alwall GFE11, Gambro AB, Lund, Sweden). With regard to vasoconstrictors, there was an increase in noradrenaline (NA) (13%, p < 0.05) and renin (PRA) (32%, p < 0.05), while arginine vasopressin and neuropeptide Y remained unaltered. Concerning vasodilators, an increase in substance P (SP) (23%, p < 0.05) and vasoactive intestinal peptide (VIP) (15%, p < 0.01) was observed, while a decrease in atrial natriuretic peptide (ANP) (17%, p < 0.05) and motilin (MOT) (24%, p < 0.01) occurred. Calcitonin gene related peptide and beta endorphin were unaltered. A decrease in blood pressure was observed, while heart rate remained unchanged. The authors conclude that the extracorporeal circulation, per se, affects plasma levels of vasoactive substances and influences vascular stability. The decrease in ANP and MOT might be due to adsorption to the dialysis membrane. The increase in some vasoconstrictors (NA, PRA) and vasodilators (SP, VIP) might be induced by the blood-artificial surface contact, or by other factors, e.g., heparin or cooling of the blood during the procedure."} {"id": "PMID:1281015", "title": "Clinical evaluation of a new synthetic protease inhibitor in open heart surgery. Effect on plasma serotonin and histamine release and blood conservation.", "content": "To achieve more physiologically successful cardiopulmonary bypass (CPB), the effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT), were examined in open heart surgery. Thirty adult patients were divided into two groups. In Group F (GpF; n = 15), 2 mg/kg/hr of FUT was administered continuously during CPB and 0.2 mg/kg/hr before and after CPB. FUT was not given to Group C patients (GpC; n = 15), who acted as controls. Serotonin and histamine levels in plasma, platelet counts, platelet adhesive function levels, and alpha 2 plasmin inhibitor-plasmin complexes (PIC) were serially measured. The serotonin level in GpF was significantly lower at 5 min of CPB than in GpC. Histamine levels in GpC decreased remarkably after starting CPB, then later recovered; by contrast, they did not decrease in GpF during CPB. At 1 hr after CPB, platelet counts were higher (p < 0.01) in GpF (54 +/- 8%) than in GpC (41 +/- 10%), and platelet adhesion was lower (p < 0.01) in GpF (7 +/- 7%) than in GpC (34 +/- 13%). The PIC was significantly less in GpF than in GpC throughout the surgery. Blood loss in GpF was significantly reduced compared with that in GpC. In conclusion, FUT attenuated chemical mediator reactions, such as plasma serotonin and histamine, and also reduced blood loss by preserving platelets and inhibiting fibrinolysis during CPB.", "contents": "Clinical evaluation of a new synthetic protease inhibitor in open heart surgery. Effect on plasma serotonin and histamine release and blood conservation. To achieve more physiologically successful cardiopulmonary bypass (CPB), the effects of a new synthetic protease inhibitor, nafamostat mesilate (FUT), were examined in open heart surgery. Thirty adult patients were divided into two groups. In Group F (GpF; n = 15), 2 mg/kg/hr of FUT was administered continuously during CPB and 0.2 mg/kg/hr before and after CPB. FUT was not given to Group C patients (GpC; n = 15), who acted as controls. Serotonin and histamine levels in plasma, platelet counts, platelet adhesive function levels, and alpha 2 plasmin inhibitor-plasmin complexes (PIC) were serially measured. The serotonin level in GpF was significantly lower at 5 min of CPB than in GpC. Histamine levels in GpC decreased remarkably after starting CPB, then later recovered; by contrast, they did not decrease in GpF during CPB. At 1 hr after CPB, platelet counts were higher (p < 0.01) in GpF (54 +/- 8%) than in GpC (41 +/- 10%), and platelet adhesion was lower (p < 0.01) in GpF (7 +/- 7%) than in GpC (34 +/- 13%). The PIC was significantly less in GpF than in GpC throughout the surgery. Blood loss in GpF was significantly reduced compared with that in GpC. In conclusion, FUT attenuated chemical mediator reactions, such as plasma serotonin and histamine, and also reduced blood loss by preserving platelets and inhibiting fibrinolysis during CPB."} {"id": "PMID:1281018", "title": "Myeloid cell kinetics in response to haemopoietic growth factors.", "content": "The morphologically recognizable cells of haemopoietic tissue comprise some 95% of the total and their kinetic performance is both flexible and adaptable to stress conditions. The effects of the common myeloid growth factors on these cells have been examined. Using the classically developed analyses of cell kinetics with tritiated thymidine labelling autoradiography, it is shown that continuously infused or repeated injections of G-CSF increases the proliferative activity of marrow haemopoietic tissue in both mouse and man, shortening the average cell cycle times by 35 and 65% respectively, amplifying neutrophil production so that levels in the peripheral blood rise 10-15-fold. This amplified production, amounting to 3-4 extra proliferation divisions, is mostly confined to the proliferatively active maturing neutrophil cell compartments. In addition, the neutrophil maturation time is also reduced, leading to a rapid and sustained release of postmitotic cells within 1-2 days, compared with the normal time of 4-6 days. Neither GM-CSF nor IL-3 generates any significant amplification of neutrophil production in mice but, in humans, GM-CSF stimulates cell proliferation in the bone marrow to a similar degree as doses G-CSF. Studies on the granulocyte-macrophage progenitor population show that the proliferation stimulus in response to GM-CSF is not confined to the maturing populations. In the maturing neutrophil precursor population, average cell cycle times are shortened by 60%, but in this case the overall maturation times are unaffected and their time of release into the circulation is normal. The response to GM-CSF, however, is not so straightforward as that to G-CSF. The peripheral half-life of the mature cells is considerably prolonged and this is consistent with some suggestion of functional impairment. In addition, a significant release of immature cells and eosinophils (also expanded in the bone marrow in response to GM-CSF) dilutes the neutrophilic response. Monocyte production is also stimulated by G- and GM-CSF and, though no direct measurement of proliferation has been made, stimulation at all stages of their proliferation, maturation and release are implied.", "contents": "Myeloid cell kinetics in response to haemopoietic growth factors. The morphologically recognizable cells of haemopoietic tissue comprise some 95% of the total and their kinetic performance is both flexible and adaptable to stress conditions. The effects of the common myeloid growth factors on these cells have been examined. Using the classically developed analyses of cell kinetics with tritiated thymidine labelling autoradiography, it is shown that continuously infused or repeated injections of G-CSF increases the proliferative activity of marrow haemopoietic tissue in both mouse and man, shortening the average cell cycle times by 35 and 65% respectively, amplifying neutrophil production so that levels in the peripheral blood rise 10-15-fold. This amplified production, amounting to 3-4 extra proliferation divisions, is mostly confined to the proliferatively active maturing neutrophil cell compartments. In addition, the neutrophil maturation time is also reduced, leading to a rapid and sustained release of postmitotic cells within 1-2 days, compared with the normal time of 4-6 days. Neither GM-CSF nor IL-3 generates any significant amplification of neutrophil production in mice but, in humans, GM-CSF stimulates cell proliferation in the bone marrow to a similar degree as doses G-CSF. Studies on the granulocyte-macrophage progenitor population show that the proliferation stimulus in response to GM-CSF is not confined to the maturing populations. In the maturing neutrophil precursor population, average cell cycle times are shortened by 60%, but in this case the overall maturation times are unaffected and their time of release into the circulation is normal. The response to GM-CSF, however, is not so straightforward as that to G-CSF. The peripheral half-life of the mature cells is considerably prolonged and this is consistent with some suggestion of functional impairment. In addition, a significant release of immature cells and eosinophils (also expanded in the bone marrow in response to GM-CSF) dilutes the neutrophilic response. Monocyte production is also stimulated by G- and GM-CSF and, though no direct measurement of proliferation has been made, stimulation at all stages of their proliferation, maturation and release are implied."} {"id": "PMID:1281016", "title": "Human intraperitoneal response to a left ventricular assist device with a Ti-6AI-4V alloy surface.", "content": "The soft tissue reaction to long-term implantation of an intraperitoneal left ventricular assist device (LVAD) was investigated. The HeartMate 1000 (Thermo Cardiosystems, Inc., Woburn, MA) is a pneumatically driven blood pump with smooth titanium alloy (Ti-6AI-4V) outer surfaces that is placed intraperitoneally in the left upper quadrant and sutured to the anterior abdominal wall. It is being used currently as a bridge to cardiac transplant, which sometimes requires extended support times. We examined the tissue capsule that formed around the rigid circular pump housing of four LVADs (duration of implant: 61, 86, 128, and 153 days) for gross, histologic, immunohistochemical, and ultrastructural analysis. Immunostaining was performed using monoclonal and polyclonal antibodies against cytoskeletal tissue markers (vimentin, desmin, alpha-smooth muscle actin), T and B lymphocytes, carcinoembryonic antigen, factor VIII, and cytokeratins (CAM 5.2 AE1/AE3, 34 beta E12, and 35 beta H11). Direct fluorescent immunolabeling for fibrinogen was also performed to characterize cell and tissue type. Histologic analysis of the 3 to 4 mm thick capsule with white, glistening inner surfaces showed fibrovascular tissue with multipotential subserosal cells (MSCs), capillary endothelium, collagen, and a few mononuclear infiltrates. The immunohistochemical profile of the MSCs differed from myofibroblasts despite a morphologic similarity. Transmission electron microscopy revealed abundant rough endoplasmic reticulum and peripherally arranged myofilaments within the spindle shaped cells. It was hypothesized that capsule formation was initiated by fibrin deposition, followed by proliferation of MSCs and subsequent formation of fibrovascular tissue.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Human intraperitoneal response to a left ventricular assist device with a Ti-6AI-4V alloy surface. The soft tissue reaction to long-term implantation of an intraperitoneal left ventricular assist device (LVAD) was investigated. The HeartMate 1000 (Thermo Cardiosystems, Inc., Woburn, MA) is a pneumatically driven blood pump with smooth titanium alloy (Ti-6AI-4V) outer surfaces that is placed intraperitoneally in the left upper quadrant and sutured to the anterior abdominal wall. It is being used currently as a bridge to cardiac transplant, which sometimes requires extended support times. We examined the tissue capsule that formed around the rigid circular pump housing of four LVADs (duration of implant: 61, 86, 128, and 153 days) for gross, histologic, immunohistochemical, and ultrastructural analysis. Immunostaining was performed using monoclonal and polyclonal antibodies against cytoskeletal tissue markers (vimentin, desmin, alpha-smooth muscle actin), T and B lymphocytes, carcinoembryonic antigen, factor VIII, and cytokeratins (CAM 5.2 AE1/AE3, 34 beta E12, and 35 beta H11). Direct fluorescent immunolabeling for fibrinogen was also performed to characterize cell and tissue type. Histologic analysis of the 3 to 4 mm thick capsule with white, glistening inner surfaces showed fibrovascular tissue with multipotential subserosal cells (MSCs), capillary endothelium, collagen, and a few mononuclear infiltrates. The immunohistochemical profile of the MSCs differed from myofibroblasts despite a morphologic similarity. Transmission electron microscopy revealed abundant rough endoplasmic reticulum and peripherally arranged myofilaments within the spindle shaped cells. It was hypothesized that capsule formation was initiated by fibrin deposition, followed by proliferation of MSCs and subsequent formation of fibrovascular tissue.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281019", "title": "Cell interaction molecules and cytokines which participate in B lymphopoiesis.", "content": "A molecular and cellular definition of the bone marrow microenvironment is rapidly contributing to our understanding of lymphohaemopoiesis. While lineage specific genes and their protein products are being identified, information is accumulating about mechanisms which may regulate their expression. Stimulation of B lymphocyte precursor replication, and other discrete functions, are being attributed to cytokines such as interleukin 7 (IL-7). The activity of these factors may be controlled at the level of synthesis, local concentration and interaction with extracellular matrix. Extremely small amounts of IL-7 are made by stromal cells, which are themselves being thoroughly studied as cloned cell lines. This in vitro characterization suggests that stromal cells can make at least 12 cytokines, that they can respond to some of those cytokines themselves, and that they retain differentiation potential. Several molecules have been identified which are probably required for recognition between cells in marrow. It is noteworthy that they belong to several previously described families of adhesion molecules and none is unique to that tissue. VCAM-1 is constitutively expressed on stromal cells in marrow and can be recognized by pre-B cells which bear the integrin VLA-4. The same pair of molecules is probably responsible for extravasation of leukocytes in other tissues during inflammation. Cell adhesion molecules are likely to work in a carefully coordinated and cooperative fashion. Their activity can be controlled by expression or, in some cases, modulated after display on the cell surface. For example, while most haemopoietic cells bear CD44, only certain cells utilize it for recognition of the ligand hyaluronate. The affinity for hyaluronate can be experimentally regulated and depends on the cytoplasmic domain of CD44. This capability for dynamic change may be important for transient interactions between cells, permitting movement of maturing precursors within and from marrow.", "contents": "Cell interaction molecules and cytokines which participate in B lymphopoiesis. A molecular and cellular definition of the bone marrow microenvironment is rapidly contributing to our understanding of lymphohaemopoiesis. While lineage specific genes and their protein products are being identified, information is accumulating about mechanisms which may regulate their expression. Stimulation of B lymphocyte precursor replication, and other discrete functions, are being attributed to cytokines such as interleukin 7 (IL-7). The activity of these factors may be controlled at the level of synthesis, local concentration and interaction with extracellular matrix. Extremely small amounts of IL-7 are made by stromal cells, which are themselves being thoroughly studied as cloned cell lines. This in vitro characterization suggests that stromal cells can make at least 12 cytokines, that they can respond to some of those cytokines themselves, and that they retain differentiation potential. Several molecules have been identified which are probably required for recognition between cells in marrow. It is noteworthy that they belong to several previously described families of adhesion molecules and none is unique to that tissue. VCAM-1 is constitutively expressed on stromal cells in marrow and can be recognized by pre-B cells which bear the integrin VLA-4. The same pair of molecules is probably responsible for extravasation of leukocytes in other tissues during inflammation. Cell adhesion molecules are likely to work in a carefully coordinated and cooperative fashion. Their activity can be controlled by expression or, in some cases, modulated after display on the cell surface. For example, while most haemopoietic cells bear CD44, only certain cells utilize it for recognition of the ligand hyaluronate. The affinity for hyaluronate can be experimentally regulated and depends on the cytoplasmic domain of CD44. This capability for dynamic change may be important for transient interactions between cells, permitting movement of maturing precursors within and from marrow."} {"id": "PMID:1281021", "title": "Mannosyl/N-acetyl-beta-D-glucosaminyl binding properties of the envelope glycoprotein of human immunodeficiency virus type 2.", "content": "We have recently demonstrated that human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein precursor gp160 (rgp160) behaves as a mannosyl/N-acetylglucosaminyl (GlcNAc) binding protein. If such a carbohydrate-binding property were of biological relevance it should be shared by other related primate immunodeficiency viruses such as HIV-2. The present study confirms this hypothesis and extends these findings by showing that HIV-2 recombinant gp140 (rgp140) specifically interacts with three affinity matrices substituted by synthetic or natural carbohydrate structures: D-mannose-divinylsulphone-agarose, para-aminophenyl-beta-D-GlcNAc-agarose and the natural glycoprotein, bovine fetuin, also coupled to agarose. Binding of rpg140 to the matrices was inhibited by alpha-D-Man17-BSA (where BSA is bovine serum albumin), beta-D-GlcNAc47-BSA and fetuin, and by glycopeptides derived from pronase-treated porcine thyroglobulin. Glycopeptides obtained after endoglycosidase H treatment of thyroglobulin had a limited inhibitory effect, whereas beta-D-Gal17-BSA and beta-D-glucan had no effect. These results indicate that, like HIV-1 envelope glycoprotein, HIV-2 rgp140 interacts with high-mannose and with the mannosyl core of complex-type N-linked glycans, as well as with the N-acetylglucosaminyl core of oligosaccharidic structures.", "contents": "Mannosyl/N-acetyl-beta-D-glucosaminyl binding properties of the envelope glycoprotein of human immunodeficiency virus type 2. We have recently demonstrated that human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein precursor gp160 (rgp160) behaves as a mannosyl/N-acetylglucosaminyl (GlcNAc) binding protein. If such a carbohydrate-binding property were of biological relevance it should be shared by other related primate immunodeficiency viruses such as HIV-2. The present study confirms this hypothesis and extends these findings by showing that HIV-2 recombinant gp140 (rgp140) specifically interacts with three affinity matrices substituted by synthetic or natural carbohydrate structures: D-mannose-divinylsulphone-agarose, para-aminophenyl-beta-D-GlcNAc-agarose and the natural glycoprotein, bovine fetuin, also coupled to agarose. Binding of rpg140 to the matrices was inhibited by alpha-D-Man17-BSA (where BSA is bovine serum albumin), beta-D-GlcNAc47-BSA and fetuin, and by glycopeptides derived from pronase-treated porcine thyroglobulin. Glycopeptides obtained after endoglycosidase H treatment of thyroglobulin had a limited inhibitory effect, whereas beta-D-Gal17-BSA and beta-D-glucan had no effect. These results indicate that, like HIV-1 envelope glycoprotein, HIV-2 rgp140 interacts with high-mannose and with the mannosyl core of complex-type N-linked glycans, as well as with the N-acetylglucosaminyl core of oligosaccharidic structures."} {"id": "PMID:1281022", "title": "Dermal cylindroma. Expression of intermediate filaments, epithelial and neuroectodermal antigens.", "content": "We report on immunohistochemical staining patterns in so-called apocrine tumors of skin with special emphasis on the dermal cylindroma. The results were compared with apocrine tubular adenoma, syringocystadenoma papilliferum and the normal eccrine sweat gland. A relationship of dermal cylindroma to the apocrine gland is suggested by expression of lysozyme and alpha 1-antichymotrypsin. The tumor shares keratin, epithelial membrane antigen (EMA) and EGF-receptor expression with eccrine and apocrine glands. The presence of intermingled cells with a coexpression of keratin and vimentin argues for a partial myoepithelia-like differentiation. Neuroectodermal antigens are missing. Therefore, dermal cylindroma is classified as an adnexal tumor of skin with a variable rate of cells of apocrine secretory, myoepithelial and undifferentiated phenotypes.", "contents": "Dermal cylindroma. Expression of intermediate filaments, epithelial and neuroectodermal antigens. We report on immunohistochemical staining patterns in so-called apocrine tumors of skin with special emphasis on the dermal cylindroma. The results were compared with apocrine tubular adenoma, syringocystadenoma papilliferum and the normal eccrine sweat gland. A relationship of dermal cylindroma to the apocrine gland is suggested by expression of lysozyme and alpha 1-antichymotrypsin. The tumor shares keratin, epithelial membrane antigen (EMA) and EGF-receptor expression with eccrine and apocrine glands. The presence of intermingled cells with a coexpression of keratin and vimentin argues for a partial myoepithelia-like differentiation. Neuroectodermal antigens are missing. Therefore, dermal cylindroma is classified as an adnexal tumor of skin with a variable rate of cells of apocrine secretory, myoepithelial and undifferentiated phenotypes."} {"id": "PMID:1281024", "title": "Treatment with recombinant human insulin-like growth factor I of children with growth hormone receptor deficiency (Laron syndrome). Kabi Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes.", "content": "Twenty-seven patients (14 female, 13 male; 3 pubertal) with growth hormone receptor deficiency (Laron syndrome) were treated with recombinant insulin-like growth factor I (IGF-I), 40-120 micrograms/kg body weight b.d., for up to 12 months. Height SDS was between -9.1 and -3.2 at the start of treatment (age, 3.7-22.9 years). Before treatment, most patients had increased basal serum concentrations of growth hormone (2.4-208 mU/l) and low serum concentrations of IGF-I (< 20-69 micrograms/l), IGF-II (69-295 micrograms/l) and IGF binding protein-3 (0.16-1.59 mg/l). In all but the two oldest patients, the growth rate increased by more than 2 cm/year compared with that before treatment. Asymptomatic hypoglycaemia (blood glucose < 3.0 mmol/l) was recorded in ten patients in 0.7% of measurements. Four patients experienced symptomatic hypoglycaemia. A transient asymptomatic decrease in serum potassium occurred in most patients after injections.", "contents": "Treatment with recombinant human insulin-like growth factor I of children with growth hormone receptor deficiency (Laron syndrome). Kabi Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes. Twenty-seven patients (14 female, 13 male; 3 pubertal) with growth hormone receptor deficiency (Laron syndrome) were treated with recombinant insulin-like growth factor I (IGF-I), 40-120 micrograms/kg body weight b.d., for up to 12 months. Height SDS was between -9.1 and -3.2 at the start of treatment (age, 3.7-22.9 years). Before treatment, most patients had increased basal serum concentrations of growth hormone (2.4-208 mU/l) and low serum concentrations of IGF-I (< 20-69 micrograms/l), IGF-II (69-295 micrograms/l) and IGF binding protein-3 (0.16-1.59 mg/l). In all but the two oldest patients, the growth rate increased by more than 2 cm/year compared with that before treatment. Asymptomatic hypoglycaemia (blood glucose < 3.0 mmol/l) was recorded in ten patients in 0.7% of measurements. Four patients experienced symptomatic hypoglycaemia. A transient asymptomatic decrease in serum potassium occurred in most patients after injections."} {"id": "PMID:1281025", "title": "Production and purification of salicylate monooxygenase from Pseudomonas cepacia ATCC 29351.", "content": "Salicylate monooxygenase (EC: 1.14.13.1) has been produced and purified from Pseudomonas cepacia ATCC 29351 which has the ability to utilise salicylate as a sole carbon source. The bacterium was grown on a defined medium containing 2% (w/v) casamino acids and 0.15% (w/v) yeast extract at 25 degrees C; salicylate monooxygenase production was induced by the presence of up to 0.7% (w/v) sodium salicylate, to a level of approximately 2% of the soluble cell protein. The enzyme was purified over 50-fold, with a recovery of about 40%, by a combination of ion exchange and hydrophobic interaction chromatography. The purified enzyme had a specific activity of 14-15 U mg-1 protein and was essentially homogeneous.", "contents": "Production and purification of salicylate monooxygenase from Pseudomonas cepacia ATCC 29351. Salicylate monooxygenase (EC: 1.14.13.1) has been produced and purified from Pseudomonas cepacia ATCC 29351 which has the ability to utilise salicylate as a sole carbon source. The bacterium was grown on a defined medium containing 2% (w/v) casamino acids and 0.15% (w/v) yeast extract at 25 degrees C; salicylate monooxygenase production was induced by the presence of up to 0.7% (w/v) sodium salicylate, to a level of approximately 2% of the soluble cell protein. The enzyme was purified over 50-fold, with a recovery of about 40%, by a combination of ion exchange and hydrophobic interaction chromatography. The purified enzyme had a specific activity of 14-15 U mg-1 protein and was essentially homogeneous."} {"id": "PMID:1281026", "title": "Recent writings on yeast recombination.", "content": "The analysis of recombination mechanisms in Saccharomyces cerevisiae produces a lively literature spanning classical genetics, enzymology and the physical analysis of intermediates. Recent papers include excellent examples from each of these areas.", "contents": "Recent writings on yeast recombination. The analysis of recombination mechanisms in Saccharomyces cerevisiae produces a lively literature spanning classical genetics, enzymology and the physical analysis of intermediates. Recent papers include excellent examples from each of these areas."} {"id": "PMID:1281027", "title": "Diversity of mechanisms in the regulation of translation in prokaryotes and lower eukaryotes.", "content": "Regulation of translation is used to control the expression of many essential and highly expressed genes. The known repertoire of molecular mechanisms for translational regulation is expanding. Recently elucidated mechanisms involve alterations in mRNA structure and modulation of the activity of translation initiation factors.", "contents": "Diversity of mechanisms in the regulation of translation in prokaryotes and lower eukaryotes. Regulation of translation is used to control the expression of many essential and highly expressed genes. The known repertoire of molecular mechanisms for translational regulation is expanding. Recently elucidated mechanisms involve alterations in mRNA structure and modulation of the activity of translation initiation factors."} {"id": "PMID:1281028", "title": "Turnover of mRNA in prokaryotes and lower eukaryotes.", "content": "The turnover of mRNA plays an important role in the regulation of gene expression. The two best understood model systems are those of the prokaryote Escherichia coli and the lower eukaryote Saccharomyces cerevisiae. Considerable progress in recent years has helped define the general pathways by which mRNA is degraded in E coli. Much less is known about the pathways of decay, or the enzymes involved, in eukaryotic cells. However, both cis-acting sequences and trans-acting factors have recently been characterized in S. cerevisiae and an indispensable role for translation has been identified. A comparison of these model species highlights both similarities and differences in mRNA turnover between prokaryotic and eukaryotic systems.", "contents": "Turnover of mRNA in prokaryotes and lower eukaryotes. The turnover of mRNA plays an important role in the regulation of gene expression. The two best understood model systems are those of the prokaryote Escherichia coli and the lower eukaryote Saccharomyces cerevisiae. Considerable progress in recent years has helped define the general pathways by which mRNA is degraded in E coli. Much less is known about the pathways of decay, or the enzymes involved, in eukaryotic cells. However, both cis-acting sequences and trans-acting factors have recently been characterized in S. cerevisiae and an indispensable role for translation has been identified. A comparison of these model species highlights both similarities and differences in mRNA turnover between prokaryotic and eukaryotic systems."} {"id": "PMID:1281030", "title": "Low molecular weight heparin in prevention of perioperative thrombosis.", "content": "To determine whether prophylactic treatment with low molecular weight heparin reduces the incidence of thrombosis in patients who have had general or orthopaedic surgery. Meta-analysis of results from 52 randomised, controlled clinical studies (29 in general surgery and 23 in orthopaedic surgery) in which low molecular weight heparin was compared with placebo, dextran, or unfractionated heparin. Patients who had had general or orthopaedic surgery. Once daily injection of a low molecular weight heparin compared with placebo, dextran, or unfractionated heparin. Incidence of deep venous thrombosis, pulmonary embolism, major haemorrhages, and death. The results confirm that low molecular weight heparins are more efficacious for the prophylactic treatment of deep venous thrombosis than placebo (common odds ratio 0.31, 95% confidence interval 0.22 to 0.43; p < 0.001) and dextran (0.44, 0.30 to 0.65; p < 0.001). The results suggest that low molecular weight heparins are also more efficacious than unfractionated heparin (0.85, 0.74 to 0.97; p = 0.02), with no significant difference in the incidence of major haemorrhages (1.06, 0.93 to 1.20; p = 0.62). Low molecular weight heparins seem to have a higher benefit to risk ratio than unfractionated heparin in preventing perioperative thrombosis. However, it remains to be shown in a suitably powered clinical trial whether low molecular weight heparin reduces the risk of fatal pulmonary embolism compared with heparin.", "contents": "Low molecular weight heparin in prevention of perioperative thrombosis. To determine whether prophylactic treatment with low molecular weight heparin reduces the incidence of thrombosis in patients who have had general or orthopaedic surgery. Meta-analysis of results from 52 randomised, controlled clinical studies (29 in general surgery and 23 in orthopaedic surgery) in which low molecular weight heparin was compared with placebo, dextran, or unfractionated heparin. Patients who had had general or orthopaedic surgery. Once daily injection of a low molecular weight heparin compared with placebo, dextran, or unfractionated heparin. Incidence of deep venous thrombosis, pulmonary embolism, major haemorrhages, and death. The results confirm that low molecular weight heparins are more efficacious for the prophylactic treatment of deep venous thrombosis than placebo (common odds ratio 0.31, 95% confidence interval 0.22 to 0.43; p < 0.001) and dextran (0.44, 0.30 to 0.65; p < 0.001). The results suggest that low molecular weight heparins are also more efficacious than unfractionated heparin (0.85, 0.74 to 0.97; p = 0.02), with no significant difference in the incidence of major haemorrhages (1.06, 0.93 to 1.20; p = 0.62). Low molecular weight heparins seem to have a higher benefit to risk ratio than unfractionated heparin in preventing perioperative thrombosis. However, it remains to be shown in a suitably powered clinical trial whether low molecular weight heparin reduces the risk of fatal pulmonary embolism compared with heparin."} {"id": "PMID:1281032", "title": "Milestones in cystic fibrosis.", "content": "The study of cystic fibrosis (CF) provides a fascinating insight into developments in medicine in the 20th century. Milestones include the first clear clinical descriptions in the 1930s, discovery of a sweat electrolyte abnormality, establishing the autosomal recessive mode of inheritance and improvements in treatment. Microdissection experiments on sweat glands allowed the main defect to be delineated as one of chloride transport. Location of the gene to chromosome 7 made prenatal diagnosis feasible and carrier detection in siblings. The CF gene--its product being the cystic fibrosis transmembrane conductance regulator (CFTR), and its major mutation Delta F508 was discovered in 1989. World-wide collaboration has resulted in discovery of more than 150 further mutations. Incorporation of CFTR into non-chloride transporting insect cells by conferring chloride transport, proved it a chloride channel. CFTR incorporated into adenovirus results in correction of the chloride transport defect in airway cells, bringing gene therapy closer.", "contents": "Milestones in cystic fibrosis. The study of cystic fibrosis (CF) provides a fascinating insight into developments in medicine in the 20th century. Milestones include the first clear clinical descriptions in the 1930s, discovery of a sweat electrolyte abnormality, establishing the autosomal recessive mode of inheritance and improvements in treatment. Microdissection experiments on sweat glands allowed the main defect to be delineated as one of chloride transport. Location of the gene to chromosome 7 made prenatal diagnosis feasible and carrier detection in siblings. The CF gene--its product being the cystic fibrosis transmembrane conductance regulator (CFTR), and its major mutation Delta F508 was discovered in 1989. World-wide collaboration has resulted in discovery of more than 150 further mutations. Incorporation of CFTR into non-chloride transporting insect cells by conferring chloride transport, proved it a chloride channel. CFTR incorporated into adenovirus results in correction of the chloride transport defect in airway cells, bringing gene therapy closer."} {"id": "PMID:1281033", "title": "Cystic fibrosis gene.", "content": "The cystic fibrosis gene, located at 7q31, spans about 230 kb of genomic DNA and contains 27 exons. The cDNA of 6.2kb would predict an 1480 amino acid protein, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR has a high degree of homology with members of the ABC-transporter super family. The predicted protein structure consists of two membrane-spanning domains, each of 6 sub-units, anchoring CFTR in the apical membrane of specialized epithelial cells, 2 nucleotide binding folds (NBF) and a regulatory (R) domain. Disease-associated mutations in the CF gene are mainly clustered in the nucleotide-binding folds. The most common mutation, occurring in 70% of CF genes in Northern Europe and North America, is the deletion of amino acid phenylalanine at position 508 in the first NBF (ie delta F508).", "contents": "Cystic fibrosis gene. The cystic fibrosis gene, located at 7q31, spans about 230 kb of genomic DNA and contains 27 exons. The cDNA of 6.2kb would predict an 1480 amino acid protein, the cystic fibrosis transmembrane conductance regulator (CFTR). CFTR has a high degree of homology with members of the ABC-transporter super family. The predicted protein structure consists of two membrane-spanning domains, each of 6 sub-units, anchoring CFTR in the apical membrane of specialized epithelial cells, 2 nucleotide binding folds (NBF) and a regulatory (R) domain. Disease-associated mutations in the CF gene are mainly clustered in the nucleotide-binding folds. The most common mutation, occurring in 70% of CF genes in Northern Europe and North America, is the deletion of amino acid phenylalanine at position 508 in the first NBF (ie delta F508)."} {"id": "PMID:1281034", "title": "Cystic fibrosis transmembrane conductance regulator (CFTR).", "content": "Since the identification of the CF gene, less than 3 years ago, progress in analysing the function of its product, the cystic fibrosis transmembrane conductance regulator (CFTR), has been remarkable. It is now clear that CFTR functions as a small conductance chloride channel in epithelial membranes. However, many other questions remain unanswered. How does a defect in this channel result in the various pathologies associated with cystic fibrosis? Does CFTR have additional functions? How do CF mutations alter the function of the protein? Tools are now available to address these and other questions. Many features of CFTR activity suggest that pharmacological interventions may be possible. Nevertheless, an enhanced understanding of CFTR function is still essential before this basic research will provide direct benefit to CF sufferers.", "contents": "Cystic fibrosis transmembrane conductance regulator (CFTR). Since the identification of the CF gene, less than 3 years ago, progress in analysing the function of its product, the cystic fibrosis transmembrane conductance regulator (CFTR), has been remarkable. It is now clear that CFTR functions as a small conductance chloride channel in epithelial membranes. However, many other questions remain unanswered. How does a defect in this channel result in the various pathologies associated with cystic fibrosis? Does CFTR have additional functions? How do CF mutations alter the function of the protein? Tools are now available to address these and other questions. Many features of CFTR activity suggest that pharmacological interventions may be possible. Nevertheless, an enhanced understanding of CFTR function is still essential before this basic research will provide direct benefit to CF sufferers."} {"id": "PMID:1281035", "title": "Abnormalities in intracellular regulation in cystic fibrosis.", "content": "Abnormalities in intracellular regulation in cystic fibrosis (CF) result from a given mutation in the cytoplasmic domain of CFTR, which renders it unable to respond correctly to agonists acting at the cell surface. This results in altered composition of epithelial secretions, which leads to some of the clinical manifestations of CF. Investigation of cyclic AMP- and Ca(2+)-mediated pathways controlling secretion is crucial for understanding how CFTR fails to respond to stimuli and how to reverse the defect in a CF cell. It should be feasible either to upregulate abnormal CFTR activity or to bypass the defect in the cell by stimulating a compensatory signalling pathway. Although their mechanism of action is unknown, one class of compounds, the methylxanthines, have been shown to reverse a fundamental CF abnormality in CF salivary cells and in non-epithelial cells overexpressing CFTR. This affords the exciting possibility that agents acting on intracellular signal transduction pathways will prove to be useful in devising new drug strategies for CF.", "contents": "Abnormalities in intracellular regulation in cystic fibrosis. Abnormalities in intracellular regulation in cystic fibrosis (CF) result from a given mutation in the cytoplasmic domain of CFTR, which renders it unable to respond correctly to agonists acting at the cell surface. This results in altered composition of epithelial secretions, which leads to some of the clinical manifestations of CF. Investigation of cyclic AMP- and Ca(2+)-mediated pathways controlling secretion is crucial for understanding how CFTR fails to respond to stimuli and how to reverse the defect in a CF cell. It should be feasible either to upregulate abnormal CFTR activity or to bypass the defect in the cell by stimulating a compensatory signalling pathway. Although their mechanism of action is unknown, one class of compounds, the methylxanthines, have been shown to reverse a fundamental CF abnormality in CF salivary cells and in non-epithelial cells overexpressing CFTR. This affords the exciting possibility that agents acting on intracellular signal transduction pathways will prove to be useful in devising new drug strategies for CF."} {"id": "PMID:1281036", "title": "Microbiology of lung infection in cystic fibrosis.", "content": "Bronchopulmonary infection in cystic fibrosis (CF) patients is associated with chronic progressive lung disease and episodes of acute exacerbation. Infection is predominantly caused by bacteria, although infections with viruses, mycoplasma and fungi may play undervalued roles. Bacteria commonly isolated from CF sputum include Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. Colonisation of the airways by mucoid, alginate-producing variants of P. aeruginosa is recognised as a major cause of pulmonary deterioration. In addition, there is now considerable concern relating to the clinical consequences of colonisation and cross-infection with P. cepacia. This review discusses the microbiology of CF focussing on the pathogenesis and epidemiology of P. aeruginosa and P. cepacia.", "contents": "Microbiology of lung infection in cystic fibrosis. Bronchopulmonary infection in cystic fibrosis (CF) patients is associated with chronic progressive lung disease and episodes of acute exacerbation. Infection is predominantly caused by bacteria, although infections with viruses, mycoplasma and fungi may play undervalued roles. Bacteria commonly isolated from CF sputum include Staphylococcus aureus, Haemophilus influenzae and Pseudomonas aeruginosa. Colonisation of the airways by mucoid, alginate-producing variants of P. aeruginosa is recognised as a major cause of pulmonary deterioration. In addition, there is now considerable concern relating to the clinical consequences of colonisation and cross-infection with P. cepacia. This review discusses the microbiology of CF focussing on the pathogenesis and epidemiology of P. aeruginosa and P. cepacia."} {"id": "PMID:1281037", "title": "Amylin increases transport of tyrosine and tryptophan into the brain.", "content": "Injection of amylin (diabetes-associated peptide) into the hypothalamus induces anorexia, increases brain metabolism of dopamine and serotonin and elevates brain level of tryptophan. When male Sprague-Dawley rats were treated with 50 mg/kg L-tryptophan and L-tyrosine ethyl ester 30 min prior to the intrahypothalamic injection of 2 micrograms amylin, brain tryptophan and tyrosine levels were selectively increased as compared to rats treated with amylin alone. Hypothalamic and striatal serotonin metabolism also appeared to be increased following the amino acid-amylin treatment combination. These results suggest that amylin may increase transport of tyrosine and tryptophan into the brain, and that the increased availability of tryptophan may contribute to increased serotonin turnover observed following intrahypothalamic amylin treatment.", "contents": "Amylin increases transport of tyrosine and tryptophan into the brain. Injection of amylin (diabetes-associated peptide) into the hypothalamus induces anorexia, increases brain metabolism of dopamine and serotonin and elevates brain level of tryptophan. When male Sprague-Dawley rats were treated with 50 mg/kg L-tryptophan and L-tyrosine ethyl ester 30 min prior to the intrahypothalamic injection of 2 micrograms amylin, brain tryptophan and tyrosine levels were selectively increased as compared to rats treated with amylin alone. Hypothalamic and striatal serotonin metabolism also appeared to be increased following the amino acid-amylin treatment combination. These results suggest that amylin may increase transport of tyrosine and tryptophan into the brain, and that the increased availability of tryptophan may contribute to increased serotonin turnover observed following intrahypothalamic amylin treatment."} {"id": "PMID:1281039", "title": "Enhancement of xanthine dehydrogenase mediated mitomycin C metabolism by dicumarol.", "content": "These studies examined the effect of dicumarol on xanthine dehydrogenase (XDH), an enzyme recently shown to bioreduce mitomycin C. Dicumarol, which has previously been shown to inhibit xanthine oxidase (XO), inhibited both XDH and XO mediated conversion of xanthine to uric acid but potentiated the metabolism of mitomycin C by XDH and XO. Formation of 2,7-diaminomitosene following mitomycin C bioactivation by XDH was increased 3-fold aerobically and 4-fold hypoxically when 20 microM dicumarol was included in the reaction mixture. XO mediated metabolism of mitomycin C hypoxically was increased approximately 50% by the inclusion of dicumarol.", "contents": "Enhancement of xanthine dehydrogenase mediated mitomycin C metabolism by dicumarol. These studies examined the effect of dicumarol on xanthine dehydrogenase (XDH), an enzyme recently shown to bioreduce mitomycin C. Dicumarol, which has previously been shown to inhibit xanthine oxidase (XO), inhibited both XDH and XO mediated conversion of xanthine to uric acid but potentiated the metabolism of mitomycin C by XDH and XO. Formation of 2,7-diaminomitosene following mitomycin C bioactivation by XDH was increased 3-fold aerobically and 4-fold hypoxically when 20 microM dicumarol was included in the reaction mixture. XO mediated metabolism of mitomycin C hypoxically was increased approximately 50% by the inclusion of dicumarol."} {"id": "PMID:1281040", "title": "Immunohistochemical differentiation of atypical hyperplasia vs. carcinoma in situ of the breast.", "content": "The distinction between atypical hyperplasia and carcinoma in situ in breast lesions can be difficult. The identification of myoepithelial cell layers may be helpful in establishing a diagnosis of proliferative breast disease vs. intraepithelial neoplasia. We reviewed pathologic material on 20 cases of atypical hyperplasia and 29 cases of carcinoma in situ. Immunohistochemical stains were employed against muscle-specific actin, S-100 protein, and cytokeratin to identify myoepithelial cells and to recognize different staining patterns. In atypical hyperplasia, muscle-specific actin staining identified myoepithelial cells in fine branching fibrovascular layers or as scattered cells between other proliferating cells. This pattern was absent in carcinoma in situ. S-100 protein showed more positive staining in atypical hyperplasia than in carcinoma in situ with patterns distinct from muscle-specific actin. Immunostaining for cytokeratin demonstrated distinctly different patterns between the two lesions. This study suggests that muscle-specific actin, S-100 protein, and cytokeratin in combination may assist in distinguishing proliferative breast disease with atypia from carcinoma in situ.", "contents": "Immunohistochemical differentiation of atypical hyperplasia vs. carcinoma in situ of the breast. The distinction between atypical hyperplasia and carcinoma in situ in breast lesions can be difficult. The identification of myoepithelial cell layers may be helpful in establishing a diagnosis of proliferative breast disease vs. intraepithelial neoplasia. We reviewed pathologic material on 20 cases of atypical hyperplasia and 29 cases of carcinoma in situ. Immunohistochemical stains were employed against muscle-specific actin, S-100 protein, and cytokeratin to identify myoepithelial cells and to recognize different staining patterns. In atypical hyperplasia, muscle-specific actin staining identified myoepithelial cells in fine branching fibrovascular layers or as scattered cells between other proliferating cells. This pattern was absent in carcinoma in situ. S-100 protein showed more positive staining in atypical hyperplasia than in carcinoma in situ with patterns distinct from muscle-specific actin. Immunostaining for cytokeratin demonstrated distinctly different patterns between the two lesions. This study suggests that muscle-specific actin, S-100 protein, and cytokeratin in combination may assist in distinguishing proliferative breast disease with atypia from carcinoma in situ."} {"id": "PMID:1281041", "title": "Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of lipiodol-transcatheter arterial embolization with and without adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.", "content": "A randomized, controlled clinical trial comparing the use of lipiodol-transcatheter arterial embolization (L-TAE) in the presence versus the absence of Adriamycin (ADR) for the treatment of hepatocellular carcinoma was conducted from August 1988 through September 1989. In all, 125 Japanese hospitals participated in this study and 289 patients were entered in the trial. The patients were randomly allocated into group A (L-TAE) or group B (L-TAE + ADR) by telephone registration. There was no significant difference in background factors between group A and group B. Additional treatment, including repeated TAE or hepatic resection, was given to 189 patients. Among the four endpoints analyzed, the rate of tumor reduction and lipiodol accumulation in the tumor did not significantly differ between the two groups. The 3-year survival values for groups A and B were 33.6% and 34.9%, respectively; the difference was not significant. The serum alpha-fetoprotein level, however, decreased to a significantly greater extent in the group that received ADR than in the group that did not (P < 0.05). This result suggests that ADR has some favorable additional effect in L-TAE for the treatment of hepatocellular carcinoma.", "contents": "Prospective and randomized clinical trial for the treatment of hepatocellular carcinoma--a comparison of lipiodol-transcatheter arterial embolization with and without adriamycin (first cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan. A randomized, controlled clinical trial comparing the use of lipiodol-transcatheter arterial embolization (L-TAE) in the presence versus the absence of Adriamycin (ADR) for the treatment of hepatocellular carcinoma was conducted from August 1988 through September 1989. In all, 125 Japanese hospitals participated in this study and 289 patients were entered in the trial. The patients were randomly allocated into group A (L-TAE) or group B (L-TAE + ADR) by telephone registration. There was no significant difference in background factors between group A and group B. Additional treatment, including repeated TAE or hepatic resection, was given to 189 patients. Among the four endpoints analyzed, the rate of tumor reduction and lipiodol accumulation in the tumor did not significantly differ between the two groups. The 3-year survival values for groups A and B were 33.6% and 34.9%, respectively; the difference was not significant. The serum alpha-fetoprotein level, however, decreased to a significantly greater extent in the group that received ADR than in the group that did not (P < 0.05). This result suggests that ADR has some favorable additional effect in L-TAE for the treatment of hepatocellular carcinoma."} {"id": "PMID:1281042", "title": "Phase II trial for combined external radiotherapy and hyperthermia for unresectable hepatoma.", "content": "Hepatocellular carcinoma is a major malignant disease in parts of Africa and Asia, including Korea. Surgical resection, which represents the best hope for cure, is limited by the extent of the disease and the high incidence of concurrent liver cirrhosis in Korea. We designed a phase II trial of combined external radiotherapy and hyperthermia for hepatocellular carcinoma that was unresectable due to either locally advanced lesions or associated liver cirrhosis so as to evaluate the efficacy and the safety of this combination regimen. This trial was performed at Yonsei Cancer Center between April 1988 and July 1988. External radiotherapy was delivered to a total dose of 3060 cGy/3.5 weeks. Hyperthermia was applied twice a week for a total of six treatment sessions using an 8-MHz radio-frequency capacitive-type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases, hyperthermia was carried out within 30 min of the radiotherapy for a period of 30-60 min. The temperature in the tumor was measured by inserting a thermocouple into the tumor mass under ultrasonographic guidance in patients who did not have a bleeding tendency. The tumor response was assessed by CT scan after completion of the designed treatment. No complete response was obtained. However, a symptomatic improvement in abdominal pain was observed in 78.6% of cases and a partial response was achieved in 40% of the patients. The most important factor affecting the tumor response was the type of tumor (single massive, 71.4%; diffuse infiltrative, 20%; multinodular, 0; P < 0.005). The 1-year survival values determined for all patients and for the partial responders were 34% and 50%, respectively. The overall median duration of survival was 6.5 months. The median duration of survival for the partial responders was longer than that for the nonresponders (11 vs 5 months; P < 0.05). A mild degree of heat sensation, fever, first-degree burns of the skin, and nausea were observed as treatment-related adverse reactions. In conclusion, although this study is being continued, the results obtained thus for indicate that combined radiotherapy and hyperthermia seem to be effective in providing local tumor control and pain palliation in unresectable hepatocellular carcinoma while producing an acceptable level of toxicity.", "contents": "Phase II trial for combined external radiotherapy and hyperthermia for unresectable hepatoma. Hepatocellular carcinoma is a major malignant disease in parts of Africa and Asia, including Korea. Surgical resection, which represents the best hope for cure, is limited by the extent of the disease and the high incidence of concurrent liver cirrhosis in Korea. We designed a phase II trial of combined external radiotherapy and hyperthermia for hepatocellular carcinoma that was unresectable due to either locally advanced lesions or associated liver cirrhosis so as to evaluate the efficacy and the safety of this combination regimen. This trial was performed at Yonsei Cancer Center between April 1988 and July 1988. External radiotherapy was delivered to a total dose of 3060 cGy/3.5 weeks. Hyperthermia was applied twice a week for a total of six treatment sessions using an 8-MHz radio-frequency capacitive-type heating device, i.e., Thermotron RF-8 and Cancermia. In all cases, hyperthermia was carried out within 30 min of the radiotherapy for a period of 30-60 min. The temperature in the tumor was measured by inserting a thermocouple into the tumor mass under ultrasonographic guidance in patients who did not have a bleeding tendency. The tumor response was assessed by CT scan after completion of the designed treatment. No complete response was obtained. However, a symptomatic improvement in abdominal pain was observed in 78.6% of cases and a partial response was achieved in 40% of the patients. The most important factor affecting the tumor response was the type of tumor (single massive, 71.4%; diffuse infiltrative, 20%; multinodular, 0; P < 0.005). The 1-year survival values determined for all patients and for the partial responders were 34% and 50%, respectively. The overall median duration of survival was 6.5 months. The median duration of survival for the partial responders was longer than that for the nonresponders (11 vs 5 months; P < 0.05). A mild degree of heat sensation, fever, first-degree burns of the skin, and nausea were observed as treatment-related adverse reactions. In conclusion, although this study is being continued, the results obtained thus for indicate that combined radiotherapy and hyperthermia seem to be effective in providing local tumor control and pain palliation in unresectable hepatocellular carcinoma while producing an acceptable level of toxicity."} {"id": "PMID:1281043", "title": "Treatment of hepatocellular carcinoma by transcatheter hepatic arterial injection of radioactive iodized oil solution.", "content": "After 12 days of culture, VX2 carcinoma cells were inoculated into the liver of 16 rabbits; 14 days later, 131I-labeled iodized oil ([131I]-Lp) suspended in lipiodol was injected into the hepatic artery. Selective accumulation of the contrast material in the tumor for an extended time was evident on X-rays and hepatic scintiphotographs. The antitumor effect was remarkable. [131I]-Lp agents warrant further examination for their clinical usefulness. Internal radiation therapy by transcatheter hepatic arterial injection of [131I]-Lp (group A) was evaluated in 9 patients with hepatocellular carcinoma (HCC, tumor stage III or IV) associated with liver cirrhosis (LC) and compared with combination therapy of Lp-TAE (group B) in 18 patients with HCC (tumor stage III or IV) associated with LC. In group A, serum AFP levels dropped rapidly in eight of the nine patients who had an elevated initial level of more than 500 ng/ml. The average reduction in tumor size was 50% in eight cases as determined by computed tomography. Histological examination of one resected liver specimen at 3 months after the third injection of [131I]-Lp revealed microscopic features highly suggestive of a radiation effect in the [131I]-Lp-containing area. The 1-year survival value for patients with HCC was estimated at 49.0% using the Kaplan-Meier method. The survival of patients treated with internal radiation therapy tended to be better than that of those treated with Lp-TAE (P = 0.119).", "contents": "Treatment of hepatocellular carcinoma by transcatheter hepatic arterial injection of radioactive iodized oil solution. After 12 days of culture, VX2 carcinoma cells were inoculated into the liver of 16 rabbits; 14 days later, 131I-labeled iodized oil ([131I]-Lp) suspended in lipiodol was injected into the hepatic artery. Selective accumulation of the contrast material in the tumor for an extended time was evident on X-rays and hepatic scintiphotographs. The antitumor effect was remarkable. [131I]-Lp agents warrant further examination for their clinical usefulness. Internal radiation therapy by transcatheter hepatic arterial injection of [131I]-Lp (group A) was evaluated in 9 patients with hepatocellular carcinoma (HCC, tumor stage III or IV) associated with liver cirrhosis (LC) and compared with combination therapy of Lp-TAE (group B) in 18 patients with HCC (tumor stage III or IV) associated with LC. In group A, serum AFP levels dropped rapidly in eight of the nine patients who had an elevated initial level of more than 500 ng/ml. The average reduction in tumor size was 50% in eight cases as determined by computed tomography. Histological examination of one resected liver specimen at 3 months after the third injection of [131I]-Lp revealed microscopic features highly suggestive of a radiation effect in the [131I]-Lp-containing area. The 1-year survival value for patients with HCC was estimated at 49.0% using the Kaplan-Meier method. The survival of patients treated with internal radiation therapy tended to be better than that of those treated with Lp-TAE (P = 0.119)."} {"id": "PMID:1281044", "title": "Changes in the plasma abnormal prothrombin level following treatment of hepatocellular carcinoma.", "content": "The Hokkaido Liver Cancer Study Group focused on the changes in PIVKA-II levels observed in 61 HCC patients after several regimens of treatment in comparison with the AFP levels and the pathophysiological characteristics of HCC. The overall positivity rate for PIVKA-II was 47%, and there was no correlation between the PIVKA-II values and the AFP levels. Accordingly, the HCC detection rate was increased by about 20% by the measurement of both markers. In all, 13 patients underwent hepatic resection, and nonsurgical therapy was carried out in the other 48 subjects. Of the 6 surgically treated patients, 5 (83%) showed a fall in PIVKA-II levels to the normal range immediately after surgery, whereas 14/29 (48%) subjects receiving nonsurgical treatment showed a decrease in PIVKA-II values. Although inconsistency between these tumor markers was detected in four treated cases, we concluded that assay for both of these two parameters may expand their clinical utility for the diagnosis of HCC and monitoring of patients after treatment.", "contents": "Changes in the plasma abnormal prothrombin level following treatment of hepatocellular carcinoma. The Hokkaido Liver Cancer Study Group focused on the changes in PIVKA-II levels observed in 61 HCC patients after several regimens of treatment in comparison with the AFP levels and the pathophysiological characteristics of HCC. The overall positivity rate for PIVKA-II was 47%, and there was no correlation between the PIVKA-II values and the AFP levels. Accordingly, the HCC detection rate was increased by about 20% by the measurement of both markers. In all, 13 patients underwent hepatic resection, and nonsurgical therapy was carried out in the other 48 subjects. Of the 6 surgically treated patients, 5 (83%) showed a fall in PIVKA-II levels to the normal range immediately after surgery, whereas 14/29 (48%) subjects receiving nonsurgical treatment showed a decrease in PIVKA-II values. Although inconsistency between these tumor markers was detected in four treated cases, we concluded that assay for both of these two parameters may expand their clinical utility for the diagnosis of HCC and monitoring of patients after treatment."} {"id": "PMID:1281045", "title": "Treatment of hepatocellular carcinoma with a CDDP-epirubicin-lipiodol suspension: a pilot clinico-pharmacological study.", "content": "Lipiodol injection is a useful method for detecting liver tumors, especially hepatocellular carcinoma (HCC). We therefore prepared and tested a new emulsion of lipiodol containing epirubicin and cis-diammine-dichloroplatinum (CDDP), drugs that are very effective against HCC. This CDDP-epirubicin-lipiodol suspension (CELS) was injected into 18 HCC patients via a celiac angiographic catheter. In 11 of these patients, CELS was followed by transcatheter arterial embolization (TAE) therapy. Clinical and pharmacological investigations were performed in all 18 patients, and the following results were obtained. CELS is pharmacologically and chemically stable, and both the results of the dissolution test and the serum levels of these two drugs indicate that slow release can be obtained. After the injection of CELS, serum levels of AFP and PIVKA-II decreased immediately, and no fatal clinical side effects were encountered. Although no statistically significant difference was observed, the survival (Kaplan-Meier method) of patients injected with CELS in the presence or absence of TAE therapy can be estimated to be much longer than that of patients receiving CDDP-lipiodol suspension injection in the presence (16 patients) or absence (6 patients) of TAE therapy. A combination of CELS injection and TAE therapy might be effective and useful for the treatment of HCC.", "contents": "Treatment of hepatocellular carcinoma with a CDDP-epirubicin-lipiodol suspension: a pilot clinico-pharmacological study. Lipiodol injection is a useful method for detecting liver tumors, especially hepatocellular carcinoma (HCC). We therefore prepared and tested a new emulsion of lipiodol containing epirubicin and cis-diammine-dichloroplatinum (CDDP), drugs that are very effective against HCC. This CDDP-epirubicin-lipiodol suspension (CELS) was injected into 18 HCC patients via a celiac angiographic catheter. In 11 of these patients, CELS was followed by transcatheter arterial embolization (TAE) therapy. Clinical and pharmacological investigations were performed in all 18 patients, and the following results were obtained. CELS is pharmacologically and chemically stable, and both the results of the dissolution test and the serum levels of these two drugs indicate that slow release can be obtained. After the injection of CELS, serum levels of AFP and PIVKA-II decreased immediately, and no fatal clinical side effects were encountered. Although no statistically significant difference was observed, the survival (Kaplan-Meier method) of patients injected with CELS in the presence or absence of TAE therapy can be estimated to be much longer than that of patients receiving CDDP-lipiodol suspension injection in the presence (16 patients) or absence (6 patients) of TAE therapy. A combination of CELS injection and TAE therapy might be effective and useful for the treatment of HCC."} {"id": "PMID:1281046", "title": "Evaluation of transcatheter arterial embolization with epirubicin-lipiodol emulsion for hepatocellular carcinoma.", "content": "A total of 18 patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) with a 4'-epi-doxorubicin (EDX)-lipiodol emulsion. Infusion of the EDX-lipiodol emulsion (EDX-L) via the hepatic artery was followed by the injection of gelatin sponge in 12 cases. The response and survival of these 12 patients following EDX-L treatment were compared with those of 42 subjects treated with a doxorubicin-lipiodol emulsion (DX-L) and those of 23 patients treated by TAE with gelatin sponge (GS) only. In the group treated with EDX-L, nine cases were AFP-positive in sera and four showed a decrease in serum AFP values to less than 10% of the pretreatment level. Seven cases showed a partial response, and nine cases showed no change in the size of the tumor. In the group treated with EDX-L, nine cases are alive, and the oldest has survived for more than 431 days since the treatment. The half-year survival value was 57%, and the 1-year survival value was 49%. These values did not differ significantly from those calculated for the group treated with DX-L. The 1-year survival value determined for patients treated with a lipiodol emulsion (EDX-L or DX-L) followed by GS was 65%, and the 2-year survival value was 39%. These results rates are significantly better than those obtained in patients treated with GS only (1-year survival, 39%; 2-year survival, 13%.", "contents": "Evaluation of transcatheter arterial embolization with epirubicin-lipiodol emulsion for hepatocellular carcinoma. A total of 18 patients with hepatocellular carcinoma (HCC) were treated by transcatheter arterial embolization (TAE) with a 4'-epi-doxorubicin (EDX)-lipiodol emulsion. Infusion of the EDX-lipiodol emulsion (EDX-L) via the hepatic artery was followed by the injection of gelatin sponge in 12 cases. The response and survival of these 12 patients following EDX-L treatment were compared with those of 42 subjects treated with a doxorubicin-lipiodol emulsion (DX-L) and those of 23 patients treated by TAE with gelatin sponge (GS) only. In the group treated with EDX-L, nine cases were AFP-positive in sera and four showed a decrease in serum AFP values to less than 10% of the pretreatment level. Seven cases showed a partial response, and nine cases showed no change in the size of the tumor. In the group treated with EDX-L, nine cases are alive, and the oldest has survived for more than 431 days since the treatment. The half-year survival value was 57%, and the 1-year survival value was 49%. These values did not differ significantly from those calculated for the group treated with DX-L. The 1-year survival value determined for patients treated with a lipiodol emulsion (EDX-L or DX-L) followed by GS was 65%, and the 2-year survival value was 39%. These results rates are significantly better than those obtained in patients treated with GS only (1-year survival, 39%; 2-year survival, 13%."} {"id": "PMID:1281047", "title": "Analysis of prognostic factors in patients with hepatocellular carcinoma treated by transcatheter arterial embolization.", "content": "We studied 240 cases of unresected hepatocellular carcinoma (HCC) using Cox's proportional hazard model to elucidate which factors would be closely related with the survival period after treatment by transcatheter arterial embolization (TAE) in the presence or absence of iodized oil. The results were as follows. The cumulative survival values obtained after TAE were 67.5% for 1 year, 32.0% for 2 years, and 20.5% for 3 years. The most significant prognostic factor was the degree of extension of tumor embolus in the portal vein or its branch. The tumor extension and the tumor type were also important factors. Age, sex, and AFP, HBsAg, and HCV Ab values were not useful as prognostic factors. This study provides a rational background for the selection of treatment for HCC. Furthermore, knowledge of the prognostic factors is useful for the management of patients, particularly in maintaining their good quality of life.", "contents": "Analysis of prognostic factors in patients with hepatocellular carcinoma treated by transcatheter arterial embolization. We studied 240 cases of unresected hepatocellular carcinoma (HCC) using Cox's proportional hazard model to elucidate which factors would be closely related with the survival period after treatment by transcatheter arterial embolization (TAE) in the presence or absence of iodized oil. The results were as follows. The cumulative survival values obtained after TAE were 67.5% for 1 year, 32.0% for 2 years, and 20.5% for 3 years. The most significant prognostic factor was the degree of extension of tumor embolus in the portal vein or its branch. The tumor extension and the tumor type were also important factors. Age, sex, and AFP, HBsAg, and HCV Ab values were not useful as prognostic factors. This study provides a rational background for the selection of treatment for HCC. Furthermore, knowledge of the prognostic factors is useful for the management of patients, particularly in maintaining their good quality of life."} {"id": "PMID:1281048", "title": "Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization and analysis of prognostic factors.", "content": "A total of 100 patients with histologically proven hepatocellular carcinoma (HCC) underwent transcatheter arterial chemoembolization (TACE) and were followed for more than 1 year and 10 months. Portal vein branch thrombosis was diagnosed in 14 patients, and extrahepatic metastasis was noted in 11 subjects. The embolization material used was iodized oil (0.1-0.2 ml/cm tumor area at its maximal diameter), which was prepared by pumping with contrast agent and then mixed with anticancer drugs; Gelfoam particles measuring 1-2 mm in size were subsequently injected. The overall cumulative 0.5- 1-, 2-, and 3-year survival rates were 81%, 57%, 31%, and 21%, respectively. Patients with an intact capsule and those with solitary lesions, especially when the tumor diameter was < 5 cm, achieved a higher survival rate. In contrast, incomplete TACE, extrahepatic metastasis, and portal vein thrombosis were associated with the worst outcome. Patients with positive HBsAG and diffuse or multiple tumors also showed a poor outcome. Early diagnosis and early treatment of HCC are the keys for the achievement of better clinical results.", "contents": "Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization and analysis of prognostic factors. A total of 100 patients with histologically proven hepatocellular carcinoma (HCC) underwent transcatheter arterial chemoembolization (TACE) and were followed for more than 1 year and 10 months. Portal vein branch thrombosis was diagnosed in 14 patients, and extrahepatic metastasis was noted in 11 subjects. The embolization material used was iodized oil (0.1-0.2 ml/cm tumor area at its maximal diameter), which was prepared by pumping with contrast agent and then mixed with anticancer drugs; Gelfoam particles measuring 1-2 mm in size were subsequently injected. The overall cumulative 0.5- 1-, 2-, and 3-year survival rates were 81%, 57%, 31%, and 21%, respectively. Patients with an intact capsule and those with solitary lesions, especially when the tumor diameter was < 5 cm, achieved a higher survival rate. In contrast, incomplete TACE, extrahepatic metastasis, and portal vein thrombosis were associated with the worst outcome. Patients with positive HBsAG and diffuse or multiple tumors also showed a poor outcome. Early diagnosis and early treatment of HCC are the keys for the achievement of better clinical results."} {"id": "PMID:1281049", "title": "Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology.", "content": "Aromatic L-amino acid decarboxylase (EC. 4.1.1.28) deficiency is a newly described inborn error of metabolism that affects serotonin and dopamine biosynthesis. The major biochemical markers for this disease are increases of L-dopa, 3-methoxytyrosine, and 5-hydroxytryptophan in urine, plasma, and cerebrospinal fluid together with decreased cerebrospinal fluid concentrations of homovanillic acid and 5-hydroxyindoleacetic acid. In addition, concentrations of vanillactic acid are increased in the urine. Specific HPLC and gas chromatography-mass spectrometry methods are described that permit the identification and measurement of these metabolites in the above body fluids. Simplified assays for human plasma L-dopa decarboxylase and liver L-dopa and 5-hydroxytryptophan decarboxylase, used to demonstrate the enzyme deficiency, are also reported.", "contents": "Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology. Aromatic L-amino acid decarboxylase (EC. 4.1.1.28) deficiency is a newly described inborn error of metabolism that affects serotonin and dopamine biosynthesis. The major biochemical markers for this disease are increases of L-dopa, 3-methoxytyrosine, and 5-hydroxytryptophan in urine, plasma, and cerebrospinal fluid together with decreased cerebrospinal fluid concentrations of homovanillic acid and 5-hydroxyindoleacetic acid. In addition, concentrations of vanillactic acid are increased in the urine. Specific HPLC and gas chromatography-mass spectrometry methods are described that permit the identification and measurement of these metabolites in the above body fluids. Simplified assays for human plasma L-dopa decarboxylase and liver L-dopa and 5-hydroxytryptophan decarboxylase, used to demonstrate the enzyme deficiency, are also reported."} {"id": "PMID:1281050", "title": "Performance of an enzyme-linked immunosorbent assay system for antibodies to hepatitis C virus with two new antigens (c11/c7).", "content": "We developed an enzyme-linked immunosorbent assay (ELISA) system for antibodies to the hepatitis C virus (HCV), using two new recombinant antigens (c11 and c7) derived from the HCV genome. The performance of this ELISA system (Imucheck HCV Ab) was examined. The CV values for both intra-assay precision and reproducibility of identifying HCV antibody in the panel sera ranged from 3.5% to 6.4%. The blood elements in serum and anticoagulants did not interfere in this ELISA system. The specificity of Imucheck HCV Ab to samples from patients with non-A, non-B (NANB)-type chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma was 93.7%, 93.5%, and 81.4%, respectively. These results are more sensitive than those obtained by the first-generation anti-HCV ELISA system. In the samples from patients with NANB-type acute hepatitis, Imucheck HCV Ab enabled detection of HCV antibodies at an early stage. This system increased the sensitivity for blood donor screening and for monitoring patients with acute hepatitis.", "contents": "Performance of an enzyme-linked immunosorbent assay system for antibodies to hepatitis C virus with two new antigens (c11/c7). We developed an enzyme-linked immunosorbent assay (ELISA) system for antibodies to the hepatitis C virus (HCV), using two new recombinant antigens (c11 and c7) derived from the HCV genome. The performance of this ELISA system (Imucheck HCV Ab) was examined. The CV values for both intra-assay precision and reproducibility of identifying HCV antibody in the panel sera ranged from 3.5% to 6.4%. The blood elements in serum and anticoagulants did not interfere in this ELISA system. The specificity of Imucheck HCV Ab to samples from patients with non-A, non-B (NANB)-type chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma was 93.7%, 93.5%, and 81.4%, respectively. These results are more sensitive than those obtained by the first-generation anti-HCV ELISA system. In the samples from patients with NANB-type acute hepatitis, Imucheck HCV Ab enabled detection of HCV antibodies at an early stage. This system increased the sensitivity for blood donor screening and for monitoring patients with acute hepatitis."} {"id": "PMID:1281051", "title": "Spuriously low concentrations of serum iron measured with generation 14 Kodak Ektachem slides: prevalence, possible causes, and partial improvement with generation 16 slides.", "content": "For sera with iron (Fe) concentrations < 4 mumol/L, Kodak Ektachem slides Generation (GEN) 14 (without ascorbic acid) yielded systematically lower results for Fe than did liquid Ferrozine-based reagents from Baker containing ascorbic acid (10 g/L, final concentration) and adapted to Cobas-Bio. During an 8-month comparison period, outliers (defined as [Fe]Cobas - [Fe]Kodak > 4 mumol/L) were seen in 21 of the 8731 sera (0.24%) tested, corresponding to < 5% of the sera with [Fe]Kodak < 4 mumol/L. In vitro addition of ascorbic acid and (or) Fe identified at least two types of outliers: type 1 (approximately 70%), characterized by [Fe]Kodak > 0.4 mumol/L, by (supra)normal Fe recovery in Kodak slides in the presence or absence of ascorbic acid (10 g/L), and by between-method differences in serum Fe (Cobas - Kodak) that were significantly correlated with serum Zn content (P < 0.0004); and type 2 (approximately 30%), tentatively ascribed to contamination by EDTA, with serum Fe by Kodak < 0.4 mumol/L and Fe recovery near 0%, both of which could be significantly and dose-dependently increased by addition of ascorbic acid (5-20 g/L). For both types of outliers, flameless atomic absorption spectrometry (AAS) yielded results that were significantly higher than concentrations by Kodak with GEN 14. Use of GEN 16 slides (containing ascorbic acid) improved concordance of Kodak results with Cobas, and hence with flameless AAS, for both types of outliers; abolished Zn dependency of results; and increased Fe results in sera with type 2 outliers, although these remained substantially lower than by Cobas. However, like other ascorbic acid-containing reagents, GEN 16 slides were more sensitive to interference by dextran-bound Fe, as assessed during in vitro addition experiments and comparisons involving samples from Fe-dextran-treated patients. GEN 16 slides are hence expected to more frequently overestimate the physiologically available protein-bound Fe in hemodialysis patients. In hospital laboratories, this new interference will probably arise more frequently than the spuriously low results with GEN 14, hence warranting further efforts in optimizing Fe slides.", "contents": "Spuriously low concentrations of serum iron measured with generation 14 Kodak Ektachem slides: prevalence, possible causes, and partial improvement with generation 16 slides. For sera with iron (Fe) concentrations < 4 mumol/L, Kodak Ektachem slides Generation (GEN) 14 (without ascorbic acid) yielded systematically lower results for Fe than did liquid Ferrozine-based reagents from Baker containing ascorbic acid (10 g/L, final concentration) and adapted to Cobas-Bio. During an 8-month comparison period, outliers (defined as [Fe]Cobas - [Fe]Kodak > 4 mumol/L) were seen in 21 of the 8731 sera (0.24%) tested, corresponding to < 5% of the sera with [Fe]Kodak < 4 mumol/L. In vitro addition of ascorbic acid and (or) Fe identified at least two types of outliers: type 1 (approximately 70%), characterized by [Fe]Kodak > 0.4 mumol/L, by (supra)normal Fe recovery in Kodak slides in the presence or absence of ascorbic acid (10 g/L), and by between-method differences in serum Fe (Cobas - Kodak) that were significantly correlated with serum Zn content (P < 0.0004); and type 2 (approximately 30%), tentatively ascribed to contamination by EDTA, with serum Fe by Kodak < 0.4 mumol/L and Fe recovery near 0%, both of which could be significantly and dose-dependently increased by addition of ascorbic acid (5-20 g/L). For both types of outliers, flameless atomic absorption spectrometry (AAS) yielded results that were significantly higher than concentrations by Kodak with GEN 14. Use of GEN 16 slides (containing ascorbic acid) improved concordance of Kodak results with Cobas, and hence with flameless AAS, for both types of outliers; abolished Zn dependency of results; and increased Fe results in sera with type 2 outliers, although these remained substantially lower than by Cobas. However, like other ascorbic acid-containing reagents, GEN 16 slides were more sensitive to interference by dextran-bound Fe, as assessed during in vitro addition experiments and comparisons involving samples from Fe-dextran-treated patients. GEN 16 slides are hence expected to more frequently overestimate the physiologically available protein-bound Fe in hemodialysis patients. In hospital laboratories, this new interference will probably arise more frequently than the spuriously low results with GEN 14, hence warranting further efforts in optimizing Fe slides."} {"id": "PMID:1281052", "title": "Allelic amino acid substitutions affect the conformation and immunoreactivity of germ-cell alkaline phosphatase phenotypes.", "content": "The gene encoding placental alkaline phosphatase (PLAP) displays a well-documented allelic polymorphism. Likewise, different phenotypes exist for the PLAP-related germ-cell alkaline phosphatase (GCAP). We investigated the extent to which various allelic GCAP positions are critical in determining the enzymatic, structural, and immunological properties of GCAP phenotypes. Three homozygous GCAP phenotypes [JEG3, BeWo, and wild-type (wt) GCAP] were analyzed and compared with a \"core\" GCAP mutant that contains the seven amino acid substitutions that are consistently different between PLAP and GCAP but are common to the three known allelic GCAP genotypes. Although some substitutions could influence the electrophoretic behavior of the phenotypes, the allelic differences did not affect the kinetic properties of GCAP. However, they did affect the immunoreactivity and conformation of the variants as detected with a panel of 18 epitope-mapped monoclonal antibodies (MAbs) to PLAP. The selective immunoreactivity of the PLAP/GCAP-discriminating MAb C2 was critically dependent on the nature of the allelic residues 133 and 361 in GCAP. Residue 133 was also important for the general stability of the molecule because BeWo and wt GCAP, which have Asn133 and Val133, respectively, instead of Met133, showed a consistently reduced heat stability compared to core GCAP and JEG3. Because the core GCAP mutant consistently shows the characteristics of wt GCAP, its use as an antigen should allow the generation of monoclonal antibodies to GCAP that will not cross-react with PLAP and whose immunoreactivity will only marginally be influenced by allelic GCAP variation.", "contents": "Allelic amino acid substitutions affect the conformation and immunoreactivity of germ-cell alkaline phosphatase phenotypes. The gene encoding placental alkaline phosphatase (PLAP) displays a well-documented allelic polymorphism. Likewise, different phenotypes exist for the PLAP-related germ-cell alkaline phosphatase (GCAP). We investigated the extent to which various allelic GCAP positions are critical in determining the enzymatic, structural, and immunological properties of GCAP phenotypes. Three homozygous GCAP phenotypes [JEG3, BeWo, and wild-type (wt) GCAP] were analyzed and compared with a \"core\" GCAP mutant that contains the seven amino acid substitutions that are consistently different between PLAP and GCAP but are common to the three known allelic GCAP genotypes. Although some substitutions could influence the electrophoretic behavior of the phenotypes, the allelic differences did not affect the kinetic properties of GCAP. However, they did affect the immunoreactivity and conformation of the variants as detected with a panel of 18 epitope-mapped monoclonal antibodies (MAbs) to PLAP. The selective immunoreactivity of the PLAP/GCAP-discriminating MAb C2 was critically dependent on the nature of the allelic residues 133 and 361 in GCAP. Residue 133 was also important for the general stability of the molecule because BeWo and wt GCAP, which have Asn133 and Val133, respectively, instead of Met133, showed a consistently reduced heat stability compared to core GCAP and JEG3. Because the core GCAP mutant consistently shows the characteristics of wt GCAP, its use as an antigen should allow the generation of monoclonal antibodies to GCAP that will not cross-react with PLAP and whose immunoreactivity will only marginally be influenced by allelic GCAP variation."} {"id": "PMID:1281054", "title": "Epidermal proliferation and keratinization following standardized elicitation with diphenylcyclopropenone.", "content": "Diphenylcyclopropenone (DCP) was applied to the upper arms of five alopecia areata patients using 10% of the concentration that had been applied previously to the scalp during topical immunotherapy. DCP applied in this concentration evoked a mild eczematous reaction. Biopsies were taken before DCP application and after 24, 48 and 96 h. A large increase in T-lymphocytes and CD14-positive cells in the dermis was seen after 24 h. Migration of these cells into the epidermis was mainly observed during the first 48 h. This was followed by epidermal proliferation as assessed by the number of Ki-67-positive nuclei and the degree of Ks8.12-binding. Both showed their main increase after 48 h; but after 24 h the increase of Ki-67-positive nuclei was significant (P < 0.04). Involucrin and filaggrin showed a gradual increase which became substantial after 96 h (both P < 0.04). As the invasion of inflammatory cells into the epidermis preceded the main increase in epidermal proliferation, cytokines are suggested as possible mediators for the initial phase of the proliferative response after DCP application.", "contents": "Epidermal proliferation and keratinization following standardized elicitation with diphenylcyclopropenone. Diphenylcyclopropenone (DCP) was applied to the upper arms of five alopecia areata patients using 10% of the concentration that had been applied previously to the scalp during topical immunotherapy. DCP applied in this concentration evoked a mild eczematous reaction. Biopsies were taken before DCP application and after 24, 48 and 96 h. A large increase in T-lymphocytes and CD14-positive cells in the dermis was seen after 24 h. Migration of these cells into the epidermis was mainly observed during the first 48 h. This was followed by epidermal proliferation as assessed by the number of Ki-67-positive nuclei and the degree of Ks8.12-binding. Both showed their main increase after 48 h; but after 24 h the increase of Ki-67-positive nuclei was significant (P < 0.04). Involucrin and filaggrin showed a gradual increase which became substantial after 96 h (both P < 0.04). As the invasion of inflammatory cells into the epidermis preceded the main increase in epidermal proliferation, cytokines are suggested as possible mediators for the initial phase of the proliferative response after DCP application."} {"id": "PMID:1281055", "title": "Killing of human leukaemia/lymphoma B cells by activated cytotoxic T lymphocytes in the presence of a bispecific monoclonal antibody (alpha CD3/alpha CD19).", "content": "Bispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL), expressing TCR alpha beta or TCR gamma delta, were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb. CD19- target cells were not killed. Fresh CD19+ leukaemia/lymphoma cells were also efficiently killed by SHR-1 preincubated CTL clones. In addition, phytohaemagglutinin (PHA) or CD3-activated IL-2 expanded peripheral blood mononuclear cells (PBMC) of normal donors did so after 2 weeks of stimulation. A concentration of 100 ng/ml of the BsAb was sufficient to obtain optimal lysis of all target cells tested. These results show that fresh human leukaemia/lymphoma cells, freshly derived from active lymphoblastic leukaemia (ALL) as well as non-Hodgkin's lymphoma (NHL) patients, can be effectively killed in the presence of this BsAb by activated T cells.", "contents": "Killing of human leukaemia/lymphoma B cells by activated cytotoxic T lymphocytes in the presence of a bispecific monoclonal antibody (alpha CD3/alpha CD19). Bispecific antibodies (BsAb) can be used to retarget T cells irrespective of their specificity to certain target cells inducing target cell lysis. We have tested the efficacy of the BsAb SHR-1, directed against the T cell antigen CD3 and the B cell antigen CD19 to induce (malignant) B cell kill by T cells as measured in a 51Cr-release assay. Two cytotoxic T cell clones (CTL), expressing TCR alpha beta or TCR gamma delta, were effective in killing CD19 expressing B cell lines at different stages of differentiation in the presence, but not in the absence, of the BsAb. CD19- target cells were not killed. Fresh CD19+ leukaemia/lymphoma cells were also efficiently killed by SHR-1 preincubated CTL clones. In addition, phytohaemagglutinin (PHA) or CD3-activated IL-2 expanded peripheral blood mononuclear cells (PBMC) of normal donors did so after 2 weeks of stimulation. A concentration of 100 ng/ml of the BsAb was sufficient to obtain optimal lysis of all target cells tested. These results show that fresh human leukaemia/lymphoma cells, freshly derived from active lymphoblastic leukaemia (ALL) as well as non-Hodgkin's lymphoma (NHL) patients, can be effectively killed in the presence of this BsAb by activated T cells."} {"id": "PMID:1281056", "title": "Antibodies to Mycobacterium paratuberculosis-specific protein antigens in Crohn's disease.", "content": "The possible role of infection with Mycobacterium paratuberculosis (MAP) for the etiopathogenesis of Crohn's disease (CD) has been a matter of long-term controversy. In addition to similarities with the pathology of ruminant paratuberculosis, DNA fingerprinting confirmed the organism isolated from gut tissue, but the specificity of the immune repertoire has not as yet been evaluated. We report here on a serological study of 29 patients with CD, 20 patients with ulcerative colitis and 18 healthy control subjects, using three antigens attributed with species-specificity and selective immunogenicity following MAP infection. Antibodies binding to the 38-kD band of MAP extract were demonstrable by the Western blot technique in 57% of CD patients. Antibody levels to the 24-kD (p24BCD) cathodic bands, determined by competition ELISA using a monospecific murine antiserum, and to the 18-kD protease-resistant purified bacterioferritin, detected by standard ELISA, were significantly elevated in 53% of CD patients. However, these three antibody specificities tested in individual CD patients did not show any correlation with each other. Thus, 18% of patients were positive for all three specificities, whilst 84% had antibodies to at least one of the specific antigens. Although the exact proportion of affected patients is yet to be defined, the serological results obtained support the view that MAP infection may play an etiological role in Crohn's disease.", "contents": "Antibodies to Mycobacterium paratuberculosis-specific protein antigens in Crohn's disease. The possible role of infection with Mycobacterium paratuberculosis (MAP) for the etiopathogenesis of Crohn's disease (CD) has been a matter of long-term controversy. In addition to similarities with the pathology of ruminant paratuberculosis, DNA fingerprinting confirmed the organism isolated from gut tissue, but the specificity of the immune repertoire has not as yet been evaluated. We report here on a serological study of 29 patients with CD, 20 patients with ulcerative colitis and 18 healthy control subjects, using three antigens attributed with species-specificity and selective immunogenicity following MAP infection. Antibodies binding to the 38-kD band of MAP extract were demonstrable by the Western blot technique in 57% of CD patients. Antibody levels to the 24-kD (p24BCD) cathodic bands, determined by competition ELISA using a monospecific murine antiserum, and to the 18-kD protease-resistant purified bacterioferritin, detected by standard ELISA, were significantly elevated in 53% of CD patients. However, these three antibody specificities tested in individual CD patients did not show any correlation with each other. Thus, 18% of patients were positive for all three specificities, whilst 84% had antibodies to at least one of the specific antigens. Although the exact proportion of affected patients is yet to be defined, the serological results obtained support the view that MAP infection may play an etiological role in Crohn's disease."} {"id": "PMID:1281057", "title": "Distribution of the PBC-specific- (M2) and the naturally-occurring mitochondrial antigen- (NOMAg) systems in plants.", "content": "In previous studies it was demonstrated that antibodies in sera from patients with primary biliary cirrhosis (PBC) and their relatives can recognize two different antigen systems in the ATPase fraction prepared from beef heart mitochondria, namely the PBC-related M2- and the naturally occurring mitochondrial antigen (NOMAg)-related epitopes. Since separation of these two antigen systems could not be achieved using mammalian mitochondria, mitochondria from a wide spectrum of plants were analysed with respect to the presence of mitochondrial antigens. Mitochondria from 29 species of plants were prepared and tested by ELISA and Western blot using marker sera from patients with PBC reacting in the Western blot with M2a,b,c,d (alpha-ketoacid-dehydrogenase complex) and NOMAg-specific sera recognizing the three major epitopes epsilon, zeta, and eta at 65, 61 and 58 kD. Naturally occurring mitochondrial antibody (NOMA)-positive marker sera reacted in the ELISA with mitochondria from all plants, and the zeta/eta positive sera gave also a positive reaction at 61/58 kD in the Western blot while the epsilon epitope could not be visualized by this method. In contrast, the M2 antigen was detected preferentially in lower plants such as algae, fungi, and ferns. Analysing these data with respect to the evolution of proteins one would have to assume that the M2 antigen was lost in most higher plants or underwent some structural alterations. Furthermore, considering the fact that the M2- and the NOMAg-related epitopes could be only partially separated, i.e. there were no plant mitochondria showing only M2 but no NOMAg, one could speculate that anti-M2 antibodies are derived from the pool of naturally occurring antibodies.", "contents": "Distribution of the PBC-specific- (M2) and the naturally-occurring mitochondrial antigen- (NOMAg) systems in plants. In previous studies it was demonstrated that antibodies in sera from patients with primary biliary cirrhosis (PBC) and their relatives can recognize two different antigen systems in the ATPase fraction prepared from beef heart mitochondria, namely the PBC-related M2- and the naturally occurring mitochondrial antigen (NOMAg)-related epitopes. Since separation of these two antigen systems could not be achieved using mammalian mitochondria, mitochondria from a wide spectrum of plants were analysed with respect to the presence of mitochondrial antigens. Mitochondria from 29 species of plants were prepared and tested by ELISA and Western blot using marker sera from patients with PBC reacting in the Western blot with M2a,b,c,d (alpha-ketoacid-dehydrogenase complex) and NOMAg-specific sera recognizing the three major epitopes epsilon, zeta, and eta at 65, 61 and 58 kD. Naturally occurring mitochondrial antibody (NOMA)-positive marker sera reacted in the ELISA with mitochondria from all plants, and the zeta/eta positive sera gave also a positive reaction at 61/58 kD in the Western blot while the epsilon epitope could not be visualized by this method. In contrast, the M2 antigen was detected preferentially in lower plants such as algae, fungi, and ferns. Analysing these data with respect to the evolution of proteins one would have to assume that the M2 antigen was lost in most higher plants or underwent some structural alterations. Furthermore, considering the fact that the M2- and the NOMAg-related epitopes could be only partially separated, i.e. there were no plant mitochondria showing only M2 but no NOMAg, one could speculate that anti-M2 antibodies are derived from the pool of naturally occurring antibodies."} {"id": "PMID:1281058", "title": "Changes in hepatic mRNA levels of acute phase proteins during rat adjuvant arthritis.", "content": "Using specific cDNA probes, we have investigated changes in hepatic mRNA concentrations of the major acute phase proteins fibrinogen, alpha 2-macroglobulin (alpha 2-MG), albumin and alpha 1-acid glycoprotein (alpha 1-AGP) during developing adjuvant arthritis in Lewis rats. Continuously increasing levels in the mRNA of the positive reactants beta-fibrinogen, alpha 2-MG and alpha 1-AGP were found during developing disease with peak levels from day 15 to 21, whereas mRNA concentrations of the negative reactant albumin decreased, reaching their lowest levels on day 11 to 15. As early as 4 days after arthritis induction, the hepatic mRNA levels of beta-fibrinogen, alpha 1-AGP and albumin were distinctly different from control values. The most dramatic changes in the hepatic mRNA levels and plasma concentrations of acute phase reactants were seen between days 11 and 21. These results indicate that overproduction of the major inflammatory cytokines IL-1, TNF-alpha and IL-6, which are now felt to be largely responsible for the acute phase response in the rat, is an early event during adjuvant arthritis and that the highest amounts are produced during the inflammatory phase of the disease. mRNA changes in the acute phase proteins alpha 1-AGP and albumin, which are mainly regulated by IL-1/TNF alpha, were more pronounced than those of alpha 2-MG and beta-fibrinogen, which are predominantly controlled by IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Changes in hepatic mRNA levels of acute phase proteins during rat adjuvant arthritis. Using specific cDNA probes, we have investigated changes in hepatic mRNA concentrations of the major acute phase proteins fibrinogen, alpha 2-macroglobulin (alpha 2-MG), albumin and alpha 1-acid glycoprotein (alpha 1-AGP) during developing adjuvant arthritis in Lewis rats. Continuously increasing levels in the mRNA of the positive reactants beta-fibrinogen, alpha 2-MG and alpha 1-AGP were found during developing disease with peak levels from day 15 to 21, whereas mRNA concentrations of the negative reactant albumin decreased, reaching their lowest levels on day 11 to 15. As early as 4 days after arthritis induction, the hepatic mRNA levels of beta-fibrinogen, alpha 1-AGP and albumin were distinctly different from control values. The most dramatic changes in the hepatic mRNA levels and plasma concentrations of acute phase reactants were seen between days 11 and 21. These results indicate that overproduction of the major inflammatory cytokines IL-1, TNF-alpha and IL-6, which are now felt to be largely responsible for the acute phase response in the rat, is an early event during adjuvant arthritis and that the highest amounts are produced during the inflammatory phase of the disease. mRNA changes in the acute phase proteins alpha 1-AGP and albumin, which are mainly regulated by IL-1/TNF alpha, were more pronounced than those of alpha 2-MG and beta-fibrinogen, which are predominantly controlled by IL-6.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281061", "title": "Influence of calcitonin treatment on the osteocalcin concentration in the algodystrophy of bone.", "content": "Algodystrophy (AD) attacks all tissues in the affected region and results in the rapid demineralization of bones. Osteocalcin (OC) and alkaline phosphatase (AP) are markers of bone turnover. Calcitonin is the treatment of choice of AD. Two groups of patients were studied: Group I (n = 8)--acute stage of AD (before and during the calcitonin treatment), Group II (n = 5)--late chronic stage of AD. In the acute stage of AD both OC level and AP activity were increased. They were normal in the chronic stage of AD. During the calcitonin treatment OC level normalized after 14 days and then increased again. During the treatment, AP activity temporarily increased and then returned to the initial level. We confirm that an increased bone turnover is observed in the acute stage of AD. Discrepancy between OC level and AP activity reflects the local metabolic disturbances. Salmon calcitonin inhibits the algodystrophic process and probably contributes to the activation of the skeletal restoration.", "contents": "Influence of calcitonin treatment on the osteocalcin concentration in the algodystrophy of bone. Algodystrophy (AD) attacks all tissues in the affected region and results in the rapid demineralization of bones. Osteocalcin (OC) and alkaline phosphatase (AP) are markers of bone turnover. Calcitonin is the treatment of choice of AD. Two groups of patients were studied: Group I (n = 8)--acute stage of AD (before and during the calcitonin treatment), Group II (n = 5)--late chronic stage of AD. In the acute stage of AD both OC level and AP activity were increased. They were normal in the chronic stage of AD. During the calcitonin treatment OC level normalized after 14 days and then increased again. During the treatment, AP activity temporarily increased and then returned to the initial level. We confirm that an increased bone turnover is observed in the acute stage of AD. Discrepancy between OC level and AP activity reflects the local metabolic disturbances. Salmon calcitonin inhibits the algodystrophic process and probably contributes to the activation of the skeletal restoration."} {"id": "PMID:1281062", "title": "The frozen shoulder: diagnosis and treatment. Prospective study of 50 cases of adhesive capsulitis.", "content": "A prospective study of randomized analysis treatment of 50 cases of frozen shoulder was carried out in 3 Swiss medical centres. Three separate aetiological groups were studied: post-traumatic (40%), neurological (14%) and idiopathic (46%). An increased radioisotope bone scan (99 mTc diphosphonate) was found in 96% of cases, regardless of aetiology. The so-called idiopathic frozen shoulder showed a scapulo-humeral increase in radioisotope uptake in several areas (in 82% of cases) without involvement of the ipsilateral carpus. Clinically, the neurological type was associated with a shoulder-hand syndrome with positive bone scan of the shoulder and the wrist in all cases. The post-traumatic type showed a diffuse (in 50% of the cases) or at several circumscribed areas (also in 50%) increase in radioisotope uptake in the shoulder. In 45% of the post-traumatic type, there was also a shoulder-hand syndrome with uptake in the wrist also. A physical treatment and early mobilization, associated with the administration of subcutaneous salmon calcitonin for 21 days (100 U Calcitonin Sandoz) had a statistically significant increased effect on pain compared to treatment with physiotherapy alone by patients with post-traumatic frozen shoulders (p < 0.02). There was no significant difference, however, in the speed of recovery of function between the two treatment groups. These observations strengthen the hypothesis that adhesive capsulitis behave like an algoneurodystrophic process.", "contents": "The frozen shoulder: diagnosis and treatment. Prospective study of 50 cases of adhesive capsulitis. A prospective study of randomized analysis treatment of 50 cases of frozen shoulder was carried out in 3 Swiss medical centres. Three separate aetiological groups were studied: post-traumatic (40%), neurological (14%) and idiopathic (46%). An increased radioisotope bone scan (99 mTc diphosphonate) was found in 96% of cases, regardless of aetiology. The so-called idiopathic frozen shoulder showed a scapulo-humeral increase in radioisotope uptake in several areas (in 82% of cases) without involvement of the ipsilateral carpus. Clinically, the neurological type was associated with a shoulder-hand syndrome with positive bone scan of the shoulder and the wrist in all cases. The post-traumatic type showed a diffuse (in 50% of the cases) or at several circumscribed areas (also in 50%) increase in radioisotope uptake in the shoulder. In 45% of the post-traumatic type, there was also a shoulder-hand syndrome with uptake in the wrist also. A physical treatment and early mobilization, associated with the administration of subcutaneous salmon calcitonin for 21 days (100 U Calcitonin Sandoz) had a statistically significant increased effect on pain compared to treatment with physiotherapy alone by patients with post-traumatic frozen shoulders (p < 0.02). There was no significant difference, however, in the speed of recovery of function between the two treatment groups. These observations strengthen the hypothesis that adhesive capsulitis behave like an algoneurodystrophic process."} {"id": "PMID:1281060", "title": "Monoclonal antibodies against partially deglycosylated colon cancer mucin that recognize Tn antigen.", "content": "In order to develop reagents that can detect the exposed core carbohydrate antigens of mucins, we have prepared monoclonal antibodies against partially deglycosylated LS174T human colon cancer mucin. The three monoclonal antibodies, 10F4, 15D3a, and 91S8, stained cancers of the colon, pancreas, stomach, breast, prostate, and lung to a greater extent than corresponding normal tissues. There was no staining of normal pancreas or breast, suggesting that these antibodies may be particularly useful for detecting cancers in these two organs. In homogenates of cultured cancer cells, antigen was detectable in three colon cancer cell lines, but not in a variety of other epithelial cancers. The epitope specificity of all three monoclonal antibodies appears to be for Tn antigen, i.e. GalNAc-alpha-Ser/Thr, based on their recognition of alpha-linked GalNAc, but not T antigen, sialyl Tn, or a range of other structures. However, the three anti-Tn antibodies differed in tissue staining specificity and in relative binding to different mucins. These monoclonal antibodies, prepared against deglycosylated colon cancer mucin, appear to be useful reagents for the immunohistochemical detection of epithelial cancers, especially pancreatic cancer and breast cancer.", "contents": "Monoclonal antibodies against partially deglycosylated colon cancer mucin that recognize Tn antigen. In order to develop reagents that can detect the exposed core carbohydrate antigens of mucins, we have prepared monoclonal antibodies against partially deglycosylated LS174T human colon cancer mucin. The three monoclonal antibodies, 10F4, 15D3a, and 91S8, stained cancers of the colon, pancreas, stomach, breast, prostate, and lung to a greater extent than corresponding normal tissues. There was no staining of normal pancreas or breast, suggesting that these antibodies may be particularly useful for detecting cancers in these two organs. In homogenates of cultured cancer cells, antigen was detectable in three colon cancer cell lines, but not in a variety of other epithelial cancers. The epitope specificity of all three monoclonal antibodies appears to be for Tn antigen, i.e. GalNAc-alpha-Ser/Thr, based on their recognition of alpha-linked GalNAc, but not T antigen, sialyl Tn, or a range of other structures. However, the three anti-Tn antibodies differed in tissue staining specificity and in relative binding to different mucins. These monoclonal antibodies, prepared against deglycosylated colon cancer mucin, appear to be useful reagents for the immunohistochemical detection of epithelial cancers, especially pancreatic cancer and breast cancer."} {"id": "PMID:1281065", "title": "[Therapy of bone metastases of the lower extremity with the KMFTR modular tumor endoprosthesis system].", "content": "During the years 1975 through 1989, 189 patients have been operated because of metastases within bones of the lower extremity. Thereof, 34 patients received an endoprosthesis of the KMFTR (Kotz Modular Femur-Tibia reconstruction system) type. In detail, the following reconstruction elements had been used: proximal femur (n = 20), distal femur (n = 7), complete femur (n = 2), proximal tibia (n = 5). At the time of follow-up examination 30 patients had died. Mean survival time after resection of metastases was 18.6 months (range 8-44 months). According to histologic judgement, in 23 cases wide or marginal resections had been performed whereas 11 patients had been operated intralesionally. In no case local recurrence as relevant to therapy was observed. At the same time-point, survival periods after detection of secondary manifestations of the malignant diseases within the remaining 4 patients were 29, 61, 73 and 125 months, respectively. The following complications were observed: luxation of the prosthesis (n = 6), transient paresis of the peroneus (n = 3), deep vein thrombosis (n = 2), pulmonary infarction (n = 1), wound healing disturbances (n = 2) and hematoma (n = 3).", "contents": "[Therapy of bone metastases of the lower extremity with the KMFTR modular tumor endoprosthesis system]. During the years 1975 through 1989, 189 patients have been operated because of metastases within bones of the lower extremity. Thereof, 34 patients received an endoprosthesis of the KMFTR (Kotz Modular Femur-Tibia reconstruction system) type. In detail, the following reconstruction elements had been used: proximal femur (n = 20), distal femur (n = 7), complete femur (n = 2), proximal tibia (n = 5). At the time of follow-up examination 30 patients had died. Mean survival time after resection of metastases was 18.6 months (range 8-44 months). According to histologic judgement, in 23 cases wide or marginal resections had been performed whereas 11 patients had been operated intralesionally. In no case local recurrence as relevant to therapy was observed. At the same time-point, survival periods after detection of secondary manifestations of the malignant diseases within the remaining 4 patients were 29, 61, 73 and 125 months, respectively. The following complications were observed: luxation of the prosthesis (n = 6), transient paresis of the peroneus (n = 3), deep vein thrombosis (n = 2), pulmonary infarction (n = 1), wound healing disturbances (n = 2) and hematoma (n = 3)."} {"id": "PMID:1281066", "title": "Reticulocyte quantification by flow cytometry, image analysis, and manual counting.", "content": "Reticulocyte counting by flow cytometry with thiazole orange was compared to manual or automated counting of new methylene blue stained blood smears. Forty-nine samples were compared for manual counting from randomly chosen clinical samples. Two hundred and eighty-nine samples from bone marrow transplant patients were compared during the period before and through chemo-irradiation and engraftment. The slopes of correlation plots were less than 1 when flow cytometric data were the dependent variable, suggesting that thiazole orange is less sensitive than new methylene blue. In a third study, 407 samples from bone marrow transplant patients were compared after increasing the thiazole orange concentration. The reticulocyte fluorescence distribution was divided into four groups of the brightest (youngest) 40, 60, 80, and 100% of reticulocytes. The slopes from regression analysis were 0.25, 0.49, 0.78, and 1.14, respectively. This demonstrates that thiazole orange is more sensitive than new methylene blue because the window of analysis includes an increased fraction of mature reticulocytes. In addition, the precision of each assay as measured. The rank order of precision from high to low was flow cytometry > image analysis >> manual counting.", "contents": "Reticulocyte quantification by flow cytometry, image analysis, and manual counting. Reticulocyte counting by flow cytometry with thiazole orange was compared to manual or automated counting of new methylene blue stained blood smears. Forty-nine samples were compared for manual counting from randomly chosen clinical samples. Two hundred and eighty-nine samples from bone marrow transplant patients were compared during the period before and through chemo-irradiation and engraftment. The slopes of correlation plots were less than 1 when flow cytometric data were the dependent variable, suggesting that thiazole orange is less sensitive than new methylene blue. In a third study, 407 samples from bone marrow transplant patients were compared after increasing the thiazole orange concentration. The reticulocyte fluorescence distribution was divided into four groups of the brightest (youngest) 40, 60, 80, and 100% of reticulocytes. The slopes from regression analysis were 0.25, 0.49, 0.78, and 1.14, respectively. This demonstrates that thiazole orange is more sensitive than new methylene blue because the window of analysis includes an increased fraction of mature reticulocytes. In addition, the precision of each assay as measured. The rank order of precision from high to low was flow cytometry > image analysis >> manual counting."} {"id": "PMID:1281068", "title": "Suppression of interferon response of bovine leukocytes during clinical and subclinical ketosis in lactating cows.", "content": "The influence of spontaneous ketosis on interferon alpha and gamma production in blood leucocytes and on PHA induced lymphocyte blastogenic response was investigated. Twenty three cows 4.13 +/- 2.8 weeks after calving were divided into three experimental groups on the basis of blood ketone bodies, glucose and free fatty acids concentrations. The leukocytes of cows with clinical symptoms and the highest concentration of ketones and free fatty acids in blood responded with the lowest levels of interferons alpha and gamma to three interferon inducers: Newcastle Disease Virus (NDV), phytohemagglutinin (PHA) and concanavalin A (ConA). Depression in interferon PHA stimulated synthesis correlated with a very low mitogenic response of blood lymphocytes. Blood leukocytes of cows with subclinical ketosis, characterized by mild clinical symptoms and a lower concentration of ketones in blood in comparison to cows with clinical ketosis, responded better to interferon and mitogenic stimulation; however, the interferon titer and blastogenesis were still lower than in leukocytes of healthy cows. Correlation between the stage of ketosis and the level of interferon production in milk leukocytes was also observed. A possible relationship between the suppression of interferon production in blood leukocytes and the increased concentration of ketone bodies in blood is discussed.", "contents": "Suppression of interferon response of bovine leukocytes during clinical and subclinical ketosis in lactating cows. The influence of spontaneous ketosis on interferon alpha and gamma production in blood leucocytes and on PHA induced lymphocyte blastogenic response was investigated. Twenty three cows 4.13 +/- 2.8 weeks after calving were divided into three experimental groups on the basis of blood ketone bodies, glucose and free fatty acids concentrations. The leukocytes of cows with clinical symptoms and the highest concentration of ketones and free fatty acids in blood responded with the lowest levels of interferons alpha and gamma to three interferon inducers: Newcastle Disease Virus (NDV), phytohemagglutinin (PHA) and concanavalin A (ConA). Depression in interferon PHA stimulated synthesis correlated with a very low mitogenic response of blood lymphocytes. Blood leukocytes of cows with subclinical ketosis, characterized by mild clinical symptoms and a lower concentration of ketones in blood in comparison to cows with clinical ketosis, responded better to interferon and mitogenic stimulation; however, the interferon titer and blastogenesis were still lower than in leukocytes of healthy cows. Correlation between the stage of ketosis and the level of interferon production in milk leukocytes was also observed. A possible relationship between the suppression of interferon production in blood leukocytes and the increased concentration of ketone bodies in blood is discussed."} {"id": "PMID:1281070", "title": "Diabetic gastroparesis. A critical reappraisal of new treatment strategies.", "content": "Delayed gastric emptying, gastroparesis, is one of the sequelae of diabetes mellitus. Symptoms may include postprandial nausea, epigastric pain, bloating, vomiting, early satiety and unpredictable blood sugar fluctuations. Nowadays diagnosis is made by the measurement of gastric emptying with a radionuclide test meal. Using this technique some 50% of diabetic patients show signs of disordered gastric emptying. Relief is best delivered by agents promoting gastric emptying. In phase II single-dose studies metoclopramide, domperidone, cisapride, erythromycin and renzapride were all able to enhance gastric evacuation of solid and liquid meals in patients with diabetic gastroparesis. A few short term studies support the efficacy of domperidone and renzapride, but long term trials are lacking. Erythromycin, mimicking the potent gastrokinetic effect of motilin, may hold considerable promise for the future. Experience with erythromycin in diabetic gastroparesis is nonetheless very limited. To some extent the therapeutic effectiveness of metoclopramide and cisapride has been established in placebo-controlled trials. In trials with a placebo-controlled crossover design, however, only metoclopramide showed a sustained positive effect. Metoclopramide, which combines gastrokinetic and antiemetic properties seems, so far, the best therapeutic option in diabetic gastroparesis. Cisapride may be considered as a good alternative in cases where limited efficacy or side effects preclude the use of metoclopramide.", "contents": "Diabetic gastroparesis. A critical reappraisal of new treatment strategies. Delayed gastric emptying, gastroparesis, is one of the sequelae of diabetes mellitus. Symptoms may include postprandial nausea, epigastric pain, bloating, vomiting, early satiety and unpredictable blood sugar fluctuations. Nowadays diagnosis is made by the measurement of gastric emptying with a radionuclide test meal. Using this technique some 50% of diabetic patients show signs of disordered gastric emptying. Relief is best delivered by agents promoting gastric emptying. In phase II single-dose studies metoclopramide, domperidone, cisapride, erythromycin and renzapride were all able to enhance gastric evacuation of solid and liquid meals in patients with diabetic gastroparesis. A few short term studies support the efficacy of domperidone and renzapride, but long term trials are lacking. Erythromycin, mimicking the potent gastrokinetic effect of motilin, may hold considerable promise for the future. Experience with erythromycin in diabetic gastroparesis is nonetheless very limited. To some extent the therapeutic effectiveness of metoclopramide and cisapride has been established in placebo-controlled trials. In trials with a placebo-controlled crossover design, however, only metoclopramide showed a sustained positive effect. Metoclopramide, which combines gastrokinetic and antiemetic properties seems, so far, the best therapeutic option in diabetic gastroparesis. Cisapride may be considered as a good alternative in cases where limited efficacy or side effects preclude the use of metoclopramide."} {"id": "PMID:1281071", "title": "Immunosuppressive drugs in renal transplantation. A review of the regimens.", "content": "Currently, expected 10-year first graft survival rates for kidneys from HLA-identical sibling, 1-haplotype-matched relative, and cadaver donors are 74, 51, and 40%, respectively. Histocompatibility, immunological conditioning with blood products, and immunosuppression with glucocorticoids, azathioprine, cyclosporin, and the antithymocyte (antilymphocyte) antibody preparations have been significant factors in the gradual improvement of kidney graft survival rates. Nearly all immunosuppression regimens are cyclosporin-based. Antithymocyte antibody induction therapy with delayed administration of cyclosporin is widely practised to avoid cyclosporin nephrotoxicity while the kidney graft is recovering from preservation injury. Late cyclosporin withdrawal results in inferior cadaver kidney transplant survival rates. Rejection crises usually respond to high dose glucocorticoid therapy. Glucocorticoid-resistant rejection usually responds to treatment with antithymocyte antibody. FK-506 is a promising new immunosuppressant that has properties similar to cyclosporin. Prophylaxis against viral, bacterial and fungal infections is necessary to reduce the morbidity of immunosuppression. The incidence of malignant conditions associated with viral infections is significantly increased with immunosuppression. New immunopharmacological agents and advances in genetic procedures may allow the induction of specific transplantation tolerance and successful xenotransplantation within the next decade.", "contents": "Immunosuppressive drugs in renal transplantation. A review of the regimens. Currently, expected 10-year first graft survival rates for kidneys from HLA-identical sibling, 1-haplotype-matched relative, and cadaver donors are 74, 51, and 40%, respectively. Histocompatibility, immunological conditioning with blood products, and immunosuppression with glucocorticoids, azathioprine, cyclosporin, and the antithymocyte (antilymphocyte) antibody preparations have been significant factors in the gradual improvement of kidney graft survival rates. Nearly all immunosuppression regimens are cyclosporin-based. Antithymocyte antibody induction therapy with delayed administration of cyclosporin is widely practised to avoid cyclosporin nephrotoxicity while the kidney graft is recovering from preservation injury. Late cyclosporin withdrawal results in inferior cadaver kidney transplant survival rates. Rejection crises usually respond to high dose glucocorticoid therapy. Glucocorticoid-resistant rejection usually responds to treatment with antithymocyte antibody. FK-506 is a promising new immunosuppressant that has properties similar to cyclosporin. Prophylaxis against viral, bacterial and fungal infections is necessary to reduce the morbidity of immunosuppression. The incidence of malignant conditions associated with viral infections is significantly increased with immunosuppression. New immunopharmacological agents and advances in genetic procedures may allow the induction of specific transplantation tolerance and successful xenotransplantation within the next decade."} {"id": "PMID:1281072", "title": "Treatment considerations in acute renal failure.", "content": "Acute renal failure (ARF) is characterised by progressive azotaemia, and for therapeutic purposes consideration of prerenal, intrinsic renal and postrenal types still holds good. Prerenal azotaemia is generally caused by loss of body fluids or blood, whereas postrenal azotaemia is effected by acute or chronic urinary tract obstruction. Provided these conditions are recognised on time and treated, they are reversible. However, delay in recognition or treatment could result in renal parenchymal damage and sustained ARF. Therefore utmost attention should be focused on identifying reversible factor(s) in the setting of ARF. Once reversible factors have been excluded, and ARF becomes sustained, a diagnosis of acute intrinsic renal failure is almost certain. Lack of natriuretic and diuretic responses to fluid challenge or infusion of furosemide (frusemide) and dopamine are further indications of this possibility. Management of acute intrinsic renal failure essentially consists of dietary control and dialysis therapy. The latter facilitates fluid and electrolyte management, but does not reduce the overall mortality. The potential benefit of parenteral hyperalimentation to promote renal function recovery must be carefully weighed against the risk of severe infectious complications.", "contents": "Treatment considerations in acute renal failure. Acute renal failure (ARF) is characterised by progressive azotaemia, and for therapeutic purposes consideration of prerenal, intrinsic renal and postrenal types still holds good. Prerenal azotaemia is generally caused by loss of body fluids or blood, whereas postrenal azotaemia is effected by acute or chronic urinary tract obstruction. Provided these conditions are recognised on time and treated, they are reversible. However, delay in recognition or treatment could result in renal parenchymal damage and sustained ARF. Therefore utmost attention should be focused on identifying reversible factor(s) in the setting of ARF. Once reversible factors have been excluded, and ARF becomes sustained, a diagnosis of acute intrinsic renal failure is almost certain. Lack of natriuretic and diuretic responses to fluid challenge or infusion of furosemide (frusemide) and dopamine are further indications of this possibility. Management of acute intrinsic renal failure essentially consists of dietary control and dialysis therapy. The latter facilitates fluid and electrolyte management, but does not reduce the overall mortality. The potential benefit of parenteral hyperalimentation to promote renal function recovery must be carefully weighed against the risk of severe infectious complications."} {"id": "PMID:1281073", "title": "Management of dysfunctional uterine bleeding.", "content": "Dysfunctional uterine bleeding, although not usually life-threatening, can cause disruption and discomfort for many women. It has often been poorly researched in the past, possibly because of the difficulty in measuring menstrual blood loss. Several different therapies are available and individual women can choose from a number of options. Nonsteroidal anti-inflammatory drugs such as mefenamic acid or indomethacin will be the first choice for many women as they have few side effects and it is only necessary to take them when menstrual bleeding occurs. When contraception is also required, combined oral contraceptives are helpful. Progestogen and danazol therapy are also effective, although side effects do occur. A new development has been the levonorgestrel-containing intrauterine contraceptive device which has been shown to result in large decreases in menstrual blood loss. For those women who would like a surgical approach but do not want to undergo hysterectomy, the relatively new technique of endometrial resection results either in amenorrhoea or reduced menstrual blood loss in the majority of women.", "contents": "Management of dysfunctional uterine bleeding. Dysfunctional uterine bleeding, although not usually life-threatening, can cause disruption and discomfort for many women. It has often been poorly researched in the past, possibly because of the difficulty in measuring menstrual blood loss. Several different therapies are available and individual women can choose from a number of options. Nonsteroidal anti-inflammatory drugs such as mefenamic acid or indomethacin will be the first choice for many women as they have few side effects and it is only necessary to take them when menstrual bleeding occurs. When contraception is also required, combined oral contraceptives are helpful. Progestogen and danazol therapy are also effective, although side effects do occur. A new development has been the levonorgestrel-containing intrauterine contraceptive device which has been shown to result in large decreases in menstrual blood loss. For those women who would like a surgical approach but do not want to undergo hysterectomy, the relatively new technique of endometrial resection results either in amenorrhoea or reduced menstrual blood loss in the majority of women."} {"id": "PMID:1281074", "title": "Ankylosing spondylitis. Current drug treatment.", "content": "The administration of drugs constitutes an important component of the therapeutic programme in ankylosing spondylitis (AS). The main objective of initiating such therapy is to reduce pain, stiffness and discomfort. There are at present 3 groups of drugs available for the management of AS. The first group is represented by drugs thought to influence the disease process itself. In this group, sulfasalazine is the only drug which is controlled trials has been shown to suppress disease activity in AS. We recommend the use of sulfasalazine in patients with high disease activity, with peripheral arthritis and in those with AS of short duration. The second group of drugs includes nonsteroidal anti-inflammatory drugs (NSAIDs), which suppress inflammation without influencing the disease process. These drugs should be administered selectively during periods of high disease activity. Moreover, 1 drug should be used in appropriate dosage before it is assumed to be inefficient. High doses of NSAIDs may be prescribed before bedtime in patients suffering from severe pain and stiffness during the night. The toxicity profile of NSAIDs includes gastrointestinal and renal side effects. The third group comprises analgesics and muscle relaxants. Such drugs should be used rather frequently in patients with longstanding AS refractory to treatment with NSAIDs. Peripheral arthritis and enthesopathy are generally managed by local injections of corticosteroids, while AS complicated by psoriasis or inflammatory bowel disease is treated as primary AS. AS occurring in juveniles is best treated with aspirin and an NSAID, although careful observation is necessary for the development of Reye's syndrome (with aspirin) and gastric irritation (with NSAIDs). When patients with AS undergo surgery, the possibility of silent gastrointestinal bleeding due to the use of NSAIDs and salicylates should not be ignored. Patients treated with oral corticosteroids should receive a bolus injection of soluble corticosteroid prior to surgical intervention. NSAIDs may be administered pre- and postoperatively to relieve stiffness induced by immobility. Rapid treatment of intervening infections and use of NSAIDs is recommended in AS complicated by renal amyloidosis. During pregnancy and lactation, ibuprofen may be the preferred drug in AS.", "contents": "Ankylosing spondylitis. Current drug treatment. The administration of drugs constitutes an important component of the therapeutic programme in ankylosing spondylitis (AS). The main objective of initiating such therapy is to reduce pain, stiffness and discomfort. There are at present 3 groups of drugs available for the management of AS. The first group is represented by drugs thought to influence the disease process itself. In this group, sulfasalazine is the only drug which is controlled trials has been shown to suppress disease activity in AS. We recommend the use of sulfasalazine in patients with high disease activity, with peripheral arthritis and in those with AS of short duration. The second group of drugs includes nonsteroidal anti-inflammatory drugs (NSAIDs), which suppress inflammation without influencing the disease process. These drugs should be administered selectively during periods of high disease activity. Moreover, 1 drug should be used in appropriate dosage before it is assumed to be inefficient. High doses of NSAIDs may be prescribed before bedtime in patients suffering from severe pain and stiffness during the night. The toxicity profile of NSAIDs includes gastrointestinal and renal side effects. The third group comprises analgesics and muscle relaxants. Such drugs should be used rather frequently in patients with longstanding AS refractory to treatment with NSAIDs. Peripheral arthritis and enthesopathy are generally managed by local injections of corticosteroids, while AS complicated by psoriasis or inflammatory bowel disease is treated as primary AS. AS occurring in juveniles is best treated with aspirin and an NSAID, although careful observation is necessary for the development of Reye's syndrome (with aspirin) and gastric irritation (with NSAIDs). When patients with AS undergo surgery, the possibility of silent gastrointestinal bleeding due to the use of NSAIDs and salicylates should not be ignored. Patients treated with oral corticosteroids should receive a bolus injection of soluble corticosteroid prior to surgical intervention. NSAIDs may be administered pre- and postoperatively to relieve stiffness induced by immobility. Rapid treatment of intervening infections and use of NSAIDs is recommended in AS complicated by renal amyloidosis. During pregnancy and lactation, ibuprofen may be the preferred drug in AS."} {"id": "PMID:1281075", "title": "Sertraline. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder.", "content": "Sertraline is a selective inhibitor of central serotonin reuptake. Thus, it enhances serotoninergic transmission--a property which appears to explain its antidepressant activity. Its elimination half-life (approximately 26 hours) makes it suitable for once daily administration. Although clinical experience with sertraline is limited, it appears to possess antidepressant efficacy similar to that of amitriptyline and dothiepin, marginally better than imipramine, and significantly better than placebo. Additionally, sertraline is the only antidepressant licensed in the UK for the prevention of recurrence of depression, and preliminary findings suggest that the drug may also be effective in the treatment of obsessive-compulsive disorder. Sertraline and other serotonin reuptake inhibitors possess tolerability advantages over tricyclic antidepressants. Sertraline has minimal anticholinergic activity, is essentially devoid of cardiovascular effects, has a wide therapeutic index and may be administered to elderly patients or those with underlying cardiovascular disorders. However, as with other serotonin reuptake inhibitors, sertraline has been associated with gastrointestinal disturbances (nausea, diarrhoea/loose stools) and male sexual dysfunction (primarily ejaculatory disturbance), although each of these effects is usually mild and transient, decreasing in frequency with continued treatment. As a drug class, serotonin reuptake inhibitors such as sertraline appear to provide significant advantages compared with the more established antidepressant agents, particularly in terms of tolerability. Although much broader clinical experience is required before sertraline's full therapeutic potential can be realised, if future studies confirm the encouraging initial findings, sertraline will undoubtedly become an important option in the treatment of depression.", "contents": "Sertraline. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Sertraline is a selective inhibitor of central serotonin reuptake. Thus, it enhances serotoninergic transmission--a property which appears to explain its antidepressant activity. Its elimination half-life (approximately 26 hours) makes it suitable for once daily administration. Although clinical experience with sertraline is limited, it appears to possess antidepressant efficacy similar to that of amitriptyline and dothiepin, marginally better than imipramine, and significantly better than placebo. Additionally, sertraline is the only antidepressant licensed in the UK for the prevention of recurrence of depression, and preliminary findings suggest that the drug may also be effective in the treatment of obsessive-compulsive disorder. Sertraline and other serotonin reuptake inhibitors possess tolerability advantages over tricyclic antidepressants. Sertraline has minimal anticholinergic activity, is essentially devoid of cardiovascular effects, has a wide therapeutic index and may be administered to elderly patients or those with underlying cardiovascular disorders. However, as with other serotonin reuptake inhibitors, sertraline has been associated with gastrointestinal disturbances (nausea, diarrhoea/loose stools) and male sexual dysfunction (primarily ejaculatory disturbance), although each of these effects is usually mild and transient, decreasing in frequency with continued treatment. As a drug class, serotonin reuptake inhibitors such as sertraline appear to provide significant advantages compared with the more established antidepressant agents, particularly in terms of tolerability. Although much broader clinical experience is required before sertraline's full therapeutic potential can be realised, if future studies confirm the encouraging initial findings, sertraline will undoubtedly become an important option in the treatment of depression."} {"id": "PMID:1281076", "title": "Nicorandil. A review of its pharmacology and therapeutic efficacy in angina pectoris.", "content": "Nicorandil belongs to the class of compounds known as potassium channel activators which are characterised by their arterial vasodilator properties. In addition, nicorandil has venodilating properties which are attributable to a nitrate group in its chemical structure. Therefore, by combining these two vasodilator mechanisms, nicorandil represents a novel type of compound for use in the treatment of angina pectoris. Furthermore, increasing experimental evidence suggests that potassium channel activation may also exert a direct cytoprotective effect by augmenting normal physiological processes which protect the heart against ischaemic events. Comparative studies of up to 3 months' duration suggest that nicorandil is equivalent in efficacy to isosorbide dinitrate, propranolol, atenolol, nifedipine or diltiazem in the treatment of stable angina. Preliminary evidence suggests that an improvement of anginal and ischaemic symptoms is maintained for up to 1 year. Whilst the efficacy of nicorandil in other types of angina has not been extensively studied, preliminary results indicate that intravenous nicorandil is as effective as isosorbide dinitrate in the treatment of unstable angina and is also effective in patients with variant angina. In addition, the limited data available indicate that nicorandil may be effective in patients with unstable and variant angina who are refractory to therapy with conventional antianginal agents, a potentially important area for further study. Headache, mostly of mild to moderate intensity was the most commonly reported adverse event, occurring in one-third of patients receiving the recommended therapeutic regimen of nicorandil 10 to 20mg twice daily. In comparative trials involving a total of 84 patients who received nicorandil, the incidence of headache was similar to that produced by isosorbide mononitrate and isosorbide dinitrate. Headache was most frequent on initiating therapy but declined with continued treatment. To date, approximately 5% of patients participating in European trials have withdrawn due to headache, although this rate may be reduced by using a lower starting dose of nicorandil (5 mg twice daily). In summary, clinical experience thus far indicates that nicorandil, with its novel combination of two distinct vasodilator mechanisms, offers an effective alternative to established vasodilator therapy with conventional nitrates and calcium antagonists in the long term treatment of stable angina pectoris. Further studies are warranted to establish whether the unique pharmacodynamic profile of nicorandil is advantageous for the treatment of other types of angina and/or the ischaemic myocardium.", "contents": "Nicorandil. A review of its pharmacology and therapeutic efficacy in angina pectoris. Nicorandil belongs to the class of compounds known as potassium channel activators which are characterised by their arterial vasodilator properties. In addition, nicorandil has venodilating properties which are attributable to a nitrate group in its chemical structure. Therefore, by combining these two vasodilator mechanisms, nicorandil represents a novel type of compound for use in the treatment of angina pectoris. Furthermore, increasing experimental evidence suggests that potassium channel activation may also exert a direct cytoprotective effect by augmenting normal physiological processes which protect the heart against ischaemic events. Comparative studies of up to 3 months' duration suggest that nicorandil is equivalent in efficacy to isosorbide dinitrate, propranolol, atenolol, nifedipine or diltiazem in the treatment of stable angina. Preliminary evidence suggests that an improvement of anginal and ischaemic symptoms is maintained for up to 1 year. Whilst the efficacy of nicorandil in other types of angina has not been extensively studied, preliminary results indicate that intravenous nicorandil is as effective as isosorbide dinitrate in the treatment of unstable angina and is also effective in patients with variant angina. In addition, the limited data available indicate that nicorandil may be effective in patients with unstable and variant angina who are refractory to therapy with conventional antianginal agents, a potentially important area for further study. Headache, mostly of mild to moderate intensity was the most commonly reported adverse event, occurring in one-third of patients receiving the recommended therapeutic regimen of nicorandil 10 to 20mg twice daily. In comparative trials involving a total of 84 patients who received nicorandil, the incidence of headache was similar to that produced by isosorbide mononitrate and isosorbide dinitrate. Headache was most frequent on initiating therapy but declined with continued treatment. To date, approximately 5% of patients participating in European trials have withdrawn due to headache, although this rate may be reduced by using a lower starting dose of nicorandil (5 mg twice daily). In summary, clinical experience thus far indicates that nicorandil, with its novel combination of two distinct vasodilator mechanisms, offers an effective alternative to established vasodilator therapy with conventional nitrates and calcium antagonists in the long term treatment of stable angina pectoris. Further studies are warranted to establish whether the unique pharmacodynamic profile of nicorandil is advantageous for the treatment of other types of angina and/or the ischaemic myocardium."} {"id": "PMID:1281077", "title": "Zalcitabine. A review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS).", "content": "Zalcitabine is an analogue of the nucleoside deoxycytidine which, when intracellularly converted to an active triphosphate metabolite, inhibits replication of human immunodeficiency virus (HIV). Zalcitabine is thought to act in the early phase of HIV replication by inhibiting reverse transcriptase and terminating the viral DNA chain. In vitro, zalcitabine is one of the more effective nucleoside analogues currently in clinical use for HIV infection, with 0.5 mumol/L concentrations completely inhibiting HIV replication in human T lymphocyte cell lines. In clinical trials, p24 antigen levels decreased and CD4 cell counts increased in patients with acquired immunodeficiency syndrome (AIDS) receiving zalcitabine > or = 0.03 mg/kg/day as monotherapy. Dose-dependent adverse effects that include peripheral neuropathy, stomatitis and rash, restrict long term use at higher dosages, and it is unclear whether zalcitabine monotherapy is as effective as zidovudine in extending survival in HIV-infected patients. Alternating or concomitant therapy with zalcitabine and zidovudine provides effective inhibition of viral replication and disease progression (as measured by improvements in CD4 cell counts) with lower and less toxic dosage regimens. At present, therefore, zalcitabine has a place in AIDS therapy both in combination with zidovudine, and as monotherapy for patients unable to tolerate zidovudine.", "contents": "Zalcitabine. A review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS). Zalcitabine is an analogue of the nucleoside deoxycytidine which, when intracellularly converted to an active triphosphate metabolite, inhibits replication of human immunodeficiency virus (HIV). Zalcitabine is thought to act in the early phase of HIV replication by inhibiting reverse transcriptase and terminating the viral DNA chain. In vitro, zalcitabine is one of the more effective nucleoside analogues currently in clinical use for HIV infection, with 0.5 mumol/L concentrations completely inhibiting HIV replication in human T lymphocyte cell lines. In clinical trials, p24 antigen levels decreased and CD4 cell counts increased in patients with acquired immunodeficiency syndrome (AIDS) receiving zalcitabine > or = 0.03 mg/kg/day as monotherapy. Dose-dependent adverse effects that include peripheral neuropathy, stomatitis and rash, restrict long term use at higher dosages, and it is unclear whether zalcitabine monotherapy is as effective as zidovudine in extending survival in HIV-infected patients. Alternating or concomitant therapy with zalcitabine and zidovudine provides effective inhibition of viral replication and disease progression (as measured by improvements in CD4 cell counts) with lower and less toxic dosage regimens. At present, therefore, zalcitabine has a place in AIDS therapy both in combination with zidovudine, and as monotherapy for patients unable to tolerate zidovudine."} {"id": "PMID:1281078", "title": "Anterior \"cheek\" electrodes are comparable to sphenoidal electrodes for the identification of ictal activity.", "content": "Sphenoidal electrodes are used to localize epileptiform activity originating in the temporal lobe during complex partial seizures. Sphenoidal electrodes, however, are semi-invasive and uncomfortable to the patient. We compared skin electrodes placed on the cheek (\"cheek electrodes\") with sphenoidal electrodes for the detection of the side and site of complex partial seizure onset. In a masked, randomized comparison of single ictal recordings in 22 patients, there were no significant differences between sphenoidal and cheek electrode montages in detecting the side or site of ictal onset (P < 0.01). Signal/noise ratios for interictal spikes were a mean 16.5% greater at sphenoidal sites compared to cheek sites (paired t test, t = 2.4, P < 0.05). This difference, however, did not influence the detection of rhythmical ictal activity in cheek and sphenoidal montages in our study, nor the assignment of side, site or time of seizure onset by unbiased readers. Recordings from cheek electrodes are comparable to those from sphenoidal electrodes and are useful for localizing ictal activity.", "contents": "Anterior \"cheek\" electrodes are comparable to sphenoidal electrodes for the identification of ictal activity. Sphenoidal electrodes are used to localize epileptiform activity originating in the temporal lobe during complex partial seizures. Sphenoidal electrodes, however, are semi-invasive and uncomfortable to the patient. We compared skin electrodes placed on the cheek (\"cheek electrodes\") with sphenoidal electrodes for the detection of the side and site of complex partial seizure onset. In a masked, randomized comparison of single ictal recordings in 22 patients, there were no significant differences between sphenoidal and cheek electrode montages in detecting the side or site of ictal onset (P < 0.01). Signal/noise ratios for interictal spikes were a mean 16.5% greater at sphenoidal sites compared to cheek sites (paired t test, t = 2.4, P < 0.05). This difference, however, did not influence the detection of rhythmical ictal activity in cheek and sphenoidal montages in our study, nor the assignment of side, site or time of seizure onset by unbiased readers. Recordings from cheek electrodes are comparable to those from sphenoidal electrodes and are useful for localizing ictal activity."} {"id": "PMID:1281079", "title": "Sleep deprivation in narcoleptic subjects: effect on sleep stages and EEG power density.", "content": "Sleep of 8 narcoleptic and 8 control subjects was recorded under baseline (i.e., prior wakefulness 16 h) and after 24 h without sleep. During both baseline and recovery total sleep time and stage 2 non-REM sleep were significantly decreased in narcoleptic subjects. Slow wave activity (i.e., EEG power density in the range of 0.75-4.5 Hz) decayed exponentially during baseline and after sleep deprivation in both narcoleptic and control subjects. During both baseline and recovery EEG power density in delta and sigma frequencies in non-REM sleep was enhanced in narcoleptic subjects relative to controls. In REM sleep differences in the same direction were present in delta and beta frequencies. After sleep deprivation EEG power density in non-REM sleep was elevated in delta and some higher frequencies in both patients and controls, but the response to sleep deprivation was stronger in narcoleptic subjects. These data show that in narcoleptic subjects regulatory processes underlying non-REM sleep homeostasis are operative and indicate that the response to sleep deprivation is stronger than in control subjects.", "contents": "Sleep deprivation in narcoleptic subjects: effect on sleep stages and EEG power density. Sleep of 8 narcoleptic and 8 control subjects was recorded under baseline (i.e., prior wakefulness 16 h) and after 24 h without sleep. During both baseline and recovery total sleep time and stage 2 non-REM sleep were significantly decreased in narcoleptic subjects. Slow wave activity (i.e., EEG power density in the range of 0.75-4.5 Hz) decayed exponentially during baseline and after sleep deprivation in both narcoleptic and control subjects. During both baseline and recovery EEG power density in delta and sigma frequencies in non-REM sleep was enhanced in narcoleptic subjects relative to controls. In REM sleep differences in the same direction were present in delta and beta frequencies. After sleep deprivation EEG power density in non-REM sleep was elevated in delta and some higher frequencies in both patients and controls, but the response to sleep deprivation was stronger in narcoleptic subjects. These data show that in narcoleptic subjects regulatory processes underlying non-REM sleep homeostasis are operative and indicate that the response to sleep deprivation is stronger than in control subjects."} {"id": "PMID:1281080", "title": "Maturation of the coherence of EEG activity in normal and learning-disabled children.", "content": "The age effect on coherence has been studied in control (98) and learning-disabled (LD, 54) school-aged children (from 6.0 to 16.8 years old). The EEG recordings were made at rest in 15 leads, and 105 pairwise combinations for coherence were calculated (each lead was compared with all the rest) for delta, theta, alpha, beta and total frequency bands. A significant increase of coherence with age was found in both groups, with a different pattern of maturation. In the control group, a significant increase with age was found in the coherences between posterior regions and vertex (Cz). A significant decrease with age in the coherence between frontal areas was observed, especially in the theta band. The LD group showed a different pattern: no significant relation with age was found in the coherence between any lead and vertex. A high effect of age on coherence between temporal regions was observed with a predominance of the left side in comparison with the contralateral and the ipsilateral. No decrease in frontal coherence was found: in the same region where the control group showed negative values with age, the LD groups had no age effect. The results obtained are discussed as differences in brain organization, in myelogenesis and synaptogenesis and an explanation of the etiology of LD is proposed.", "contents": "Maturation of the coherence of EEG activity in normal and learning-disabled children. The age effect on coherence has been studied in control (98) and learning-disabled (LD, 54) school-aged children (from 6.0 to 16.8 years old). The EEG recordings were made at rest in 15 leads, and 105 pairwise combinations for coherence were calculated (each lead was compared with all the rest) for delta, theta, alpha, beta and total frequency bands. A significant increase of coherence with age was found in both groups, with a different pattern of maturation. In the control group, a significant increase with age was found in the coherences between posterior regions and vertex (Cz). A significant decrease with age in the coherence between frontal areas was observed, especially in the theta band. The LD group showed a different pattern: no significant relation with age was found in the coherence between any lead and vertex. A high effect of age on coherence between temporal regions was observed with a predominance of the left side in comparison with the contralateral and the ipsilateral. No decrease in frontal coherence was found: in the same region where the control group showed negative values with age, the LD groups had no age effect. The results obtained are discussed as differences in brain organization, in myelogenesis and synaptogenesis and an explanation of the etiology of LD is proposed."} {"id": "PMID:1281081", "title": "A comparison of quantitative EEG frequency analysis and conventional EEG in patients with focal brain lesions.", "content": "The sensitivity and specificity of quantified EEG frequency analysis (EEGFA) were assessed in a group of patients with CT or MRI verified unilateral cerebral lesions and compared with the results of conventional EEG interpretations. Digital EEG recordings were obtained in 25 patients and 25 normal control subjects during performance of an alerting task. Recording artifacts were carefully eliminated. The results of EEGFA were then statistically compared with those of 75 additional normal subjects in the same age range. Complete conventional EEGs were blindly interpreted by two independent electroencephalographers using a structured reporting procedure. We observed similar overall sensitivities for the two methods. Optimal yield for EEGFA was associated with the use of longer edited EEG lengths, longitudinal bipolar montage, and normative data based on total EEG power. In those recordings with normal or mildly abnormal EEG backgrounds the two techniques were to an extent complimentary, each detecting abnormalities missed by the other. In such circumstances EEGFA may be useful as an extension of conventional EEG interpretation.", "contents": "A comparison of quantitative EEG frequency analysis and conventional EEG in patients with focal brain lesions. The sensitivity and specificity of quantified EEG frequency analysis (EEGFA) were assessed in a group of patients with CT or MRI verified unilateral cerebral lesions and compared with the results of conventional EEG interpretations. Digital EEG recordings were obtained in 25 patients and 25 normal control subjects during performance of an alerting task. Recording artifacts were carefully eliminated. The results of EEGFA were then statistically compared with those of 75 additional normal subjects in the same age range. Complete conventional EEGs were blindly interpreted by two independent electroencephalographers using a structured reporting procedure. We observed similar overall sensitivities for the two methods. Optimal yield for EEGFA was associated with the use of longer edited EEG lengths, longitudinal bipolar montage, and normative data based on total EEG power. In those recordings with normal or mildly abnormal EEG backgrounds the two techniques were to an extent complimentary, each detecting abnormalities missed by the other. In such circumstances EEGFA may be useful as an extension of conventional EEG interpretation."} {"id": "PMID:1281082", "title": "EEG in liver transplantation: visual and computerized analysis.", "content": "We prospectively evaluated 40 liver transplant candidates (including 28 recipients) with visually scored or computerized EEG. As expected, EEG frequencies rose significantly after successful transplant (P < 0.01). For all subjects, but especially for the transplant recipients, higher frequencies on computerized EEG at baseline had a strong association with survival at 18 months (P < 0.001). A logistic regression model allowed estimation of the odds for survival and indicated less than 50% long-term survival with central-occipital mean frequencies below 7.6 c/sec. Visual EEG scores closely paralleled the quantitative results, but only the latter were amenable to formal statistical analysis. EEG had much stronger predictive value for survival than serum albumin, although albumin improved more significantly in the months after transplantation.", "contents": "EEG in liver transplantation: visual and computerized analysis. We prospectively evaluated 40 liver transplant candidates (including 28 recipients) with visually scored or computerized EEG. As expected, EEG frequencies rose significantly after successful transplant (P < 0.01). For all subjects, but especially for the transplant recipients, higher frequencies on computerized EEG at baseline had a strong association with survival at 18 months (P < 0.001). A logistic regression model allowed estimation of the odds for survival and indicated less than 50% long-term survival with central-occipital mean frequencies below 7.6 c/sec. Visual EEG scores closely paralleled the quantitative results, but only the latter were amenable to formal statistical analysis. EEG had much stronger predictive value for survival than serum albumin, although albumin improved more significantly in the months after transplantation."} {"id": "PMID:1281083", "title": "Half-field sinusoidally modulated light stimulation at subject's alpha frequency.", "content": "Interhemispheric responses of alpha activity were investigated by use of half-field sinusoidally modulated light (SML) stimulation at the subject's alpha frequency. The left and right visual half-fields as well as full-field were separately stimulated by the SML. The power spectrum of SML responses, averaged with Wiener filtering, was obtained at the left and the right occipital area (O1 and O2) in 11 normal subjects. Power in each hemisphere, phase difference and coherence between O1 and O2 were estimated at an alpha frequency. A laterality index of power was defined as (P(l)-P(r))/(P(l) + P(r)) where P(l) is a power value at O1, and P(r) at O2. In most of the subjects, laterality index decreased in the order: left half-field, full-field and right half-field stimulation. This relationship revealed greater SML responses on the ipsilateral occipital area. There were significant differences in laterality index among 3 visual field conditions, thus showing that full-field responses ranged in lateralization between the left and right half-field responses in most of the subjects. This hemispheric distribution suggests that half-field SML stimulation affected alpha activity selectively in each hemisphere, mostly in the ipsilateral hemisphere.", "contents": "Half-field sinusoidally modulated light stimulation at subject's alpha frequency. Interhemispheric responses of alpha activity were investigated by use of half-field sinusoidally modulated light (SML) stimulation at the subject's alpha frequency. The left and right visual half-fields as well as full-field were separately stimulated by the SML. The power spectrum of SML responses, averaged with Wiener filtering, was obtained at the left and the right occipital area (O1 and O2) in 11 normal subjects. Power in each hemisphere, phase difference and coherence between O1 and O2 were estimated at an alpha frequency. A laterality index of power was defined as (P(l)-P(r))/(P(l) + P(r)) where P(l) is a power value at O1, and P(r) at O2. In most of the subjects, laterality index decreased in the order: left half-field, full-field and right half-field stimulation. This relationship revealed greater SML responses on the ipsilateral occipital area. There were significant differences in laterality index among 3 visual field conditions, thus showing that full-field responses ranged in lateralization between the left and right half-field responses in most of the subjects. This hemispheric distribution suggests that half-field SML stimulation affected alpha activity selectively in each hemisphere, mostly in the ipsilateral hemisphere."} {"id": "PMID:1281084", "title": "Frontocentral DC-potential shifts predicting behavior with or without a motor task.", "content": "This study was designed to investigate the predictive value of the event-related potentials (ERPs) preceding the initiation of a difficult perceptual-memory task and to investigate whether these ERPs require a motor movement on the part of the subject for their occurrence. Across 4 conditions the DC-potential shifts were recorded from 23 right-handed subjects using DC amplifiers. Although the start of each trial began with a ready signal, the conditions differed in that the subjects initiated the task by a button press in 2 conditions and the computer initiated it in 2 others without a press. The results showed that, especially in the frontocentral electrode sites, the DC-potential shifts which began those trials ending in correct performance were more negative relative to those trials ending in an incorrect response. Those conditions which required the subjects to self-initiate the trial and those which were initiated by the computer showed similar results indicating that the negative DC-potential shifts preceding correct performance are neither produced by nor depend on a task initiating motor movement. The onset of the DC-potential shifts preceded task initiation by up to 4.1 sec indicating that they were more than the Bereitschaftspotential.", "contents": "Frontocentral DC-potential shifts predicting behavior with or without a motor task. This study was designed to investigate the predictive value of the event-related potentials (ERPs) preceding the initiation of a difficult perceptual-memory task and to investigate whether these ERPs require a motor movement on the part of the subject for their occurrence. Across 4 conditions the DC-potential shifts were recorded from 23 right-handed subjects using DC amplifiers. Although the start of each trial began with a ready signal, the conditions differed in that the subjects initiated the task by a button press in 2 conditions and the computer initiated it in 2 others without a press. The results showed that, especially in the frontocentral electrode sites, the DC-potential shifts which began those trials ending in correct performance were more negative relative to those trials ending in an incorrect response. Those conditions which required the subjects to self-initiate the trial and those which were initiated by the computer showed similar results indicating that the negative DC-potential shifts preceding correct performance are neither produced by nor depend on a task initiating motor movement. The onset of the DC-potential shifts preceded task initiation by up to 4.1 sec indicating that they were more than the Bereitschaftspotential."} {"id": "PMID:1281085", "title": "Alterations in brain electrical activity caused by magnetic fields: detecting the detection process.", "content": "Static and 60 Hz magnetic fields, 0.78 gauss, were applied individually and combined to each of 20 human subjects during 2 sec epochs, and the effect on the EEG was determined by comparing the power spectrum obtained during field exposure with that from control epochs. All but one subject exhibited field-induced alterations in the EEG; most subjects exhibited increased EEG activity at 2 or more frequencies within 1-18.5 Hz. The field-induced changes were recorded more often at the central and parietal electrodes than at the occipital electrodes. The responses observed during application of combined static and alternating fields did not differ from the sum of the responses observed when the fields were applied individually, even though the exposure conditions were specifically chosen to favor the hypothesized ion-resonance mechanism of interaction involving Ca2+. The data support the view that detection loci for magnetic fields exist within the nervous system.", "contents": "Alterations in brain electrical activity caused by magnetic fields: detecting the detection process. Static and 60 Hz magnetic fields, 0.78 gauss, were applied individually and combined to each of 20 human subjects during 2 sec epochs, and the effect on the EEG was determined by comparing the power spectrum obtained during field exposure with that from control epochs. All but one subject exhibited field-induced alterations in the EEG; most subjects exhibited increased EEG activity at 2 or more frequencies within 1-18.5 Hz. The field-induced changes were recorded more often at the central and parietal electrodes than at the occipital electrodes. The responses observed during application of combined static and alternating fields did not differ from the sum of the responses observed when the fields were applied individually, even though the exposure conditions were specifically chosen to favor the hypothesized ion-resonance mechanism of interaction involving Ca2+. The data support the view that detection loci for magnetic fields exist within the nervous system."} {"id": "PMID:1281086", "title": "Development of data reconstruction system of paper-recorded EEG: method and its evaluation.", "content": "A new system by which paper-recorded EEG can be converted to computer treatable digital data was developed. It consists simply of an image scanner and a microcomputer. The performance of the system was evaluated and found to perform well in data reconstruction. The system makes it possible to apply various computer analyses to EEGs recorded on paper.", "contents": "Development of data reconstruction system of paper-recorded EEG: method and its evaluation. A new system by which paper-recorded EEG can be converted to computer treatable digital data was developed. It consists simply of an image scanner and a microcomputer. The performance of the system was evaluated and found to perform well in data reconstruction. The system makes it possible to apply various computer analyses to EEGs recorded on paper."} {"id": "PMID:1281089", "title": "Native horizontal ultrathin polyacrylamide gel electrophoresis of proteins under basic and acidic conditions.", "content": "The preparation of homogeneous ultrathin native polyacrylamide gels, using a basic as well as an acidic buffer system is described. The basic buffer system consists of Tris-HC1/Tris-glycine, the same buffer as in sodium dodecyl sulfate (SDS)-gel electrophoresis but without SDS. The acidic system uses potassium acetate, pH 4.3, as gel buffer and beta-alanine, pH 4.6, acetic acid as electrolytes. The gels are covalently bound on glass plates. Binding of acidic gels requires a special pretreatment of glass plates. The whole procedure is simple and extraordinarily fast: 100-120 min from the start of gel preparation to the end of electrophoresis. Coomassie staining is done in 40 min and silver staining in 90 min. The native gels are excellently suited for diffusion blotting. Further attractive properties of these gels are easy handling, simple drying and dimensional stability.", "contents": "Native horizontal ultrathin polyacrylamide gel electrophoresis of proteins under basic and acidic conditions. The preparation of homogeneous ultrathin native polyacrylamide gels, using a basic as well as an acidic buffer system is described. The basic buffer system consists of Tris-HC1/Tris-glycine, the same buffer as in sodium dodecyl sulfate (SDS)-gel electrophoresis but without SDS. The acidic system uses potassium acetate, pH 4.3, as gel buffer and beta-alanine, pH 4.6, acetic acid as electrolytes. The gels are covalently bound on glass plates. Binding of acidic gels requires a special pretreatment of glass plates. The whole procedure is simple and extraordinarily fast: 100-120 min from the start of gel preparation to the end of electrophoresis. Coomassie staining is done in 40 min and silver staining in 90 min. The native gels are excellently suited for diffusion blotting. Further attractive properties of these gels are easy handling, simple drying and dimensional stability."} {"id": "PMID:1281090", "title": "Improving the detection of proteins after transfer to polyvinylidene difluoride membranes.", "content": "N-Terminal sequence analysis of proteins separated by two-dimensional polyacrylamide gel electrophoresis and transferred onto polyvinylidene difluoride (PVDF) membranes has become the method for molecular characterization of proteins contained in biological samples. However, the proteins of lower abundance cannot be sequenced directly, without improving the technique. We have studied a drying method on several PVDF membranes including Trans-Blott, Immobilon P and Problott. Using Amido Black, Coomassie Brilliant Blue R-250 and Ponceau S, we have obtained, in comparison with the non-dried membranes, an enormous increase in the number of detectable proteins.", "contents": "Improving the detection of proteins after transfer to polyvinylidene difluoride membranes. N-Terminal sequence analysis of proteins separated by two-dimensional polyacrylamide gel electrophoresis and transferred onto polyvinylidene difluoride (PVDF) membranes has become the method for molecular characterization of proteins contained in biological samples. However, the proteins of lower abundance cannot be sequenced directly, without improving the technique. We have studied a drying method on several PVDF membranes including Trans-Blott, Immobilon P and Problott. Using Amido Black, Coomassie Brilliant Blue R-250 and Ponceau S, we have obtained, in comparison with the non-dried membranes, an enormous increase in the number of detectable proteins."} {"id": "PMID:1281091", "title": "Detection of the hypusine-containing protein (HP = eIF-5A) in crude yeast extracts by two-dimensional western blots.", "content": "The hypusine-containing protein (HP) with its unique modification of a specific lysine residue resulting in the amino acid hypusine is highly conserved among all eukaryotes and is also found in Archaebacteria. Studies of the protein function in translational processes showed a stimulatory effect in the methionyl puromycin assay, but not in in vitro translation of native mRNA. It was therefore also designated as eIF-5A. To further investigate the role of HP in cellular metabolism, we purified the protein from Saccharomyces cerevisiae and raised polyclonal antibodies in chicken. Immunoglobulin preparations from the eggs of the immunized hens were used for Western blot analysis of HP in crude yeast extracts. For those studies, the soluble protein fraction of the yeast was resolved on two-dimensional gels (first dimension: isoelectric focusing using an immobilized pH gradient (IPG), pH 4-7; second dimension: sodium dodecyl sulfate-polyacrylamide gel electrophoresis, 12% T) and subsequently blotted onto Fluorotrans membrane. Anodic versus cathodic application of the extracts of the IPG strips was compared.", "contents": "Detection of the hypusine-containing protein (HP = eIF-5A) in crude yeast extracts by two-dimensional western blots. The hypusine-containing protein (HP) with its unique modification of a specific lysine residue resulting in the amino acid hypusine is highly conserved among all eukaryotes and is also found in Archaebacteria. Studies of the protein function in translational processes showed a stimulatory effect in the methionyl puromycin assay, but not in in vitro translation of native mRNA. It was therefore also designated as eIF-5A. To further investigate the role of HP in cellular metabolism, we purified the protein from Saccharomyces cerevisiae and raised polyclonal antibodies in chicken. Immunoglobulin preparations from the eggs of the immunized hens were used for Western blot analysis of HP in crude yeast extracts. For those studies, the soluble protein fraction of the yeast was resolved on two-dimensional gels (first dimension: isoelectric focusing using an immobilized pH gradient (IPG), pH 4-7; second dimension: sodium dodecyl sulfate-polyacrylamide gel electrophoresis, 12% T) and subsequently blotted onto Fluorotrans membrane. Anodic versus cathodic application of the extracts of the IPG strips was compared."} {"id": "PMID:1281092", "title": "Two-dimensional electrophoresis analysis of human serum proteins during the acute-phase response.", "content": "The serum of patients with meningitis, due to infection by Haemophilus influenzae type b, was analyzed. Several known acute-phase proteins were separated by two-dimensional electrophoresis and estimated quantitatively. In addition, hitherto undescribed reactants were recognized. Gels were calibrated and relevant spots related to master spot numbers in the human serum protein database.", "contents": "Two-dimensional electrophoresis analysis of human serum proteins during the acute-phase response. The serum of patients with meningitis, due to infection by Haemophilus influenzae type b, was analyzed. Several known acute-phase proteins were separated by two-dimensional electrophoresis and estimated quantitatively. In addition, hitherto undescribed reactants were recognized. Gels were calibrated and relevant spots related to master spot numbers in the human serum protein database."} {"id": "PMID:1281093", "title": "Comparison of the cellular protein composition of aortic smooth muscle cells in vivo and in vitro by two-dimensional gel electrophoresis.", "content": "Vascular smooth muscle cells are of major interest for the evaluation of atherosclerotic processes. By the use of two-dimensional gel electrophoresis and subsequent silver staining we investigated the protein expression of smooth muscle cells in the native thoracic aorta, immediately after enzymatic disaggregation, in subconfluent proliferating and in postconfluent nonproliferating primary cell cultures. Compared to the native thoracic aorta the protein composition of smooth muscle cells in cell culture is changed dramatically. Furthermore, significant differences in protein expression between proliferating and nonproliferating smooth muscle cells in cell culture were found.", "contents": "Comparison of the cellular protein composition of aortic smooth muscle cells in vivo and in vitro by two-dimensional gel electrophoresis. Vascular smooth muscle cells are of major interest for the evaluation of atherosclerotic processes. By the use of two-dimensional gel electrophoresis and subsequent silver staining we investigated the protein expression of smooth muscle cells in the native thoracic aorta, immediately after enzymatic disaggregation, in subconfluent proliferating and in postconfluent nonproliferating primary cell cultures. Compared to the native thoracic aorta the protein composition of smooth muscle cells in cell culture is changed dramatically. Furthermore, significant differences in protein expression between proliferating and nonproliferating smooth muscle cells in cell culture were found."} {"id": "PMID:1281096", "title": "Tyrosine phosphorylation and the mechanism of signal transduction by the B-lymphocyte antigen receptor.", "content": "Lymphocytes provide a powerful defense against infectious agents with their exquisite ability to distinguish between macromolecules of the host and macromolecules of foreign invaders. This ability derives from the antigen receptors, which are created from precursor minigenes by a series of genetic-recombination reactions [1, 2] and from cellular mechanisms that inactivate lymphocytes expressing self-reactive antigen receptors [3, 4]. Central to the problem of distinguishing self from non-self is the means by which these antigen receptors recognize antigen and transmit the information of that recognition to the interior of the cell. This information ultimately leads to lymphocyte activation or inactivation, depending upon the context. In this review, I shall summarize recent advances in understanding the structural elements of the antigen receptor complex of B lymphocytes and in understanding the signal-transduction events initiated by this receptor.", "contents": "Tyrosine phosphorylation and the mechanism of signal transduction by the B-lymphocyte antigen receptor. Lymphocytes provide a powerful defense against infectious agents with their exquisite ability to distinguish between macromolecules of the host and macromolecules of foreign invaders. This ability derives from the antigen receptors, which are created from precursor minigenes by a series of genetic-recombination reactions [1, 2] and from cellular mechanisms that inactivate lymphocytes expressing self-reactive antigen receptors [3, 4]. Central to the problem of distinguishing self from non-self is the means by which these antigen receptors recognize antigen and transmit the information of that recognition to the interior of the cell. This information ultimately leads to lymphocyte activation or inactivation, depending upon the context. In this review, I shall summarize recent advances in understanding the structural elements of the antigen receptor complex of B lymphocytes and in understanding the signal-transduction events initiated by this receptor."} {"id": "PMID:1281094", "title": "Detection of polypeptides and amylase isoenzyme modifications related to malting quality during malting process of barley by two-dimensional electrophoresis and isoelectric focusing with immobilized pH gradients.", "content": "Two cultivars (\"Alexis\" and \"Lenka\") of contrasting final attenuation values were malted, and the protein and amylase isoenzyme composition, as well as the change in protein and amylase isoenzyme composition during malting, was investigated by two-dimensional polyacrylamide gel electrophoresis of total proteins, and isoelectric focusing of amylase isoenzymes, respectively. Isoelectric focusing demonstrated that significant differences exist between the amylase isoenzyme patterns of the two cultivars, suggesting a correlation between the presence of certain amylase isoenzyme bands and final attenuation. This finding was confirmed by analysis of 36 barley cultivars with a wide range of quality. It was shown that all cultivars which are of low or, at best, moderate final attenuation values exhibit the amylase band \"B\" (isoelectric point approximately 6.8), whereas those cultivars which are predominantly of high malting grade do not possess this \"B\" isoenzyme band, but exhibit the pronounced \"A\" isoenzyme band (isoelectric point approximately 6.5) instead, suggesting that these isoenzymes (which we suppose to be beta-amylases) can be utilized to predict the final attenuation values of unknown barley samples or new lines. However, \"final attenuation\" is a complex function. Preliminary results of two-dimensional gel electrophoresis indicate that other factors, such as total amount of amylases, or a 19 kDa A hordein-like polypeptide, which was degraded faster in the low malting grade cultivar \"Lenka\", may also have a role in determining quality.", "contents": "Detection of polypeptides and amylase isoenzyme modifications related to malting quality during malting process of barley by two-dimensional electrophoresis and isoelectric focusing with immobilized pH gradients. Two cultivars (\"Alexis\" and \"Lenka\") of contrasting final attenuation values were malted, and the protein and amylase isoenzyme composition, as well as the change in protein and amylase isoenzyme composition during malting, was investigated by two-dimensional polyacrylamide gel electrophoresis of total proteins, and isoelectric focusing of amylase isoenzymes, respectively. Isoelectric focusing demonstrated that significant differences exist between the amylase isoenzyme patterns of the two cultivars, suggesting a correlation between the presence of certain amylase isoenzyme bands and final attenuation. This finding was confirmed by analysis of 36 barley cultivars with a wide range of quality. It was shown that all cultivars which are of low or, at best, moderate final attenuation values exhibit the amylase band \"B\" (isoelectric point approximately 6.8), whereas those cultivars which are predominantly of high malting grade do not possess this \"B\" isoenzyme band, but exhibit the pronounced \"A\" isoenzyme band (isoelectric point approximately 6.5) instead, suggesting that these isoenzymes (which we suppose to be beta-amylases) can be utilized to predict the final attenuation values of unknown barley samples or new lines. However, \"final attenuation\" is a complex function. Preliminary results of two-dimensional gel electrophoresis indicate that other factors, such as total amount of amylases, or a 19 kDa A hordein-like polypeptide, which was degraded faster in the low malting grade cultivar \"Lenka\", may also have a role in determining quality."} {"id": "PMID:1281097", "title": "Characterization of S1 nuclease. Involvement of carboxylate groups in metal binding.", "content": "Modification of the carboxylate groups of purified S1 nuclease resulted in a loss of its single-stranded DNAase, RNAase and phosphomonoesterase activities. The inactivation was due to the removal of zinc atoms from the enzyme and this in turn was dependent on the degree of modification. While the removal of one zinc atom resulted in the partial inactivation of the enzyme, removal of the remaining zinc atoms resulted in the complete inactivation of the enzyme. Similar results were obtained when the purified enzyme was incubated with various concentrations of the metal chelator, EDTA. The EDTA-(1 mM)-treated enzyme, depleted of one zinc atom, showing 40-45% residual activity, when incubated with 1 mM Zn2+ or 1 mM Co2+, regained a significant amount of its initial activity towards all the substrates. However, Woodward's-Reagent-K-modified enzyme depleted of one zinc atom and having the same level of activity (40-45%) could not regain its activity, indicating that the carboxylate groups are involved in the metal binding. Data obtained with carboxylate-group modification, EDTA-treatment, reconstitution with metal ions, zinc estimation and CD analysis of the enzyme suggests that, out of three zinc atoms present in S1 nuclease, zinc I is easily replaceable and is probably involved in the catalytic activity while zinc II and zinc III are involved in maintaining the enzyme structure.", "contents": "Characterization of S1 nuclease. Involvement of carboxylate groups in metal binding. Modification of the carboxylate groups of purified S1 nuclease resulted in a loss of its single-stranded DNAase, RNAase and phosphomonoesterase activities. The inactivation was due to the removal of zinc atoms from the enzyme and this in turn was dependent on the degree of modification. While the removal of one zinc atom resulted in the partial inactivation of the enzyme, removal of the remaining zinc atoms resulted in the complete inactivation of the enzyme. Similar results were obtained when the purified enzyme was incubated with various concentrations of the metal chelator, EDTA. The EDTA-(1 mM)-treated enzyme, depleted of one zinc atom, showing 40-45% residual activity, when incubated with 1 mM Zn2+ or 1 mM Co2+, regained a significant amount of its initial activity towards all the substrates. However, Woodward's-Reagent-K-modified enzyme depleted of one zinc atom and having the same level of activity (40-45%) could not regain its activity, indicating that the carboxylate groups are involved in the metal binding. Data obtained with carboxylate-group modification, EDTA-treatment, reconstitution with metal ions, zinc estimation and CD analysis of the enzyme suggests that, out of three zinc atoms present in S1 nuclease, zinc I is easily replaceable and is probably involved in the catalytic activity while zinc II and zinc III are involved in maintaining the enzyme structure."} {"id": "PMID:1281095", "title": "Application of sequential extraction procedures and glycoprotein blotting for the characterization of the 2-D polypeptide patterns of barley seed proteins.", "content": "Barley (Hordeum vulgare L.) proteins were sequentially extracted from ground seeds with Tris-HCl buffer, 55% 2-propanol, 55% 2-propanol containing 1% dithiothreitol, and 6 M urea containing 2% Nonidet P-40 and 1% dithiothreitol. The protein composition of these solubility fractions was then analyzed by high resolution two-dimensional gel electrophoresis with immobilized pH gradient 4-9 in the first dimension, followed by silver staining and glycoprotein blotting, respectively, for a more detailed characterization of the two-dimensional polypeptide pattern of barley seed proteins.", "contents": "Application of sequential extraction procedures and glycoprotein blotting for the characterization of the 2-D polypeptide patterns of barley seed proteins. Barley (Hordeum vulgare L.) proteins were sequentially extracted from ground seeds with Tris-HCl buffer, 55% 2-propanol, 55% 2-propanol containing 1% dithiothreitol, and 6 M urea containing 2% Nonidet P-40 and 1% dithiothreitol. The protein composition of these solubility fractions was then analyzed by high resolution two-dimensional gel electrophoresis with immobilized pH gradient 4-9 in the first dimension, followed by silver staining and glycoprotein blotting, respectively, for a more detailed characterization of the two-dimensional polypeptide pattern of barley seed proteins."} {"id": "PMID:1281098", "title": "The structure of the O-antigenic polysaccharide from lipopolysaccharide of Vibrio cholerae strain H11 (non-O1).", "content": "After acid degradation of the lipopolysaccharide (LPS) of Vibrio cholerae strain H11 (non-O1), a tetrasaccharide was obtained, the structure of which was determined by quantitative and methylation analyses, periodate oxidation, one- and two-dimensional NMR spectroscopy, and fast-atom-bombardment and four-sector tandem mass spectrometry as beta-D-GalANGro-(1-3)-beta-D-QuiNAc-(1-4)-alpha-D-GalANGr o-(1-4)-NeuAc, in which GalANGro is N-galacturonoyl-2-aminoglycerol and QuiN 2-amino-2,6-dideoxy-glucopyranose. In addition, the trisaccharide beta-D-GalANGro-(1-3)-beta-D-QuiNAc-(1-4)-D-altro-hept ulose and the disaccharide alpha-D-GalANGro-(1-4)-NeuAc were isolated from acid-degraded lipopolysaccharide; the occurrence of sedoheptulose in lipopolysaccharide has not been described before. Based on the result of methylation analysis showing that galacturonic acid was the terminal sugar of the polysaccharide chain, and on the assumption that the tri- and the disaccharide represented the reducing and the non-reducing ends of the polysaccharide, respectively, the chemical structure of the O-specific chain of V. cholerae H11 is proposed as alpha-D-GalANGro-(1-4)-alpha-NeuAc-(2-3)-beta-D-GalANGro-(1- 3)-beta-D-QuiNAc- (1-[4)-alpha-D-GalANGro-(1-4)-alpha-NeuAc-(2-3)-beta-D-GalANGro -(1-3)-beta-D- QuiNAc-(1-]n-(1-4)-D-altro-heptulose. However, other possible structures can not be ruled out since the tri- and the disaccharide could be localised at different positions.", "contents": "The structure of the O-antigenic polysaccharide from lipopolysaccharide of Vibrio cholerae strain H11 (non-O1). After acid degradation of the lipopolysaccharide (LPS) of Vibrio cholerae strain H11 (non-O1), a tetrasaccharide was obtained, the structure of which was determined by quantitative and methylation analyses, periodate oxidation, one- and two-dimensional NMR spectroscopy, and fast-atom-bombardment and four-sector tandem mass spectrometry as beta-D-GalANGro-(1-3)-beta-D-QuiNAc-(1-4)-alpha-D-GalANGr o-(1-4)-NeuAc, in which GalANGro is N-galacturonoyl-2-aminoglycerol and QuiN 2-amino-2,6-dideoxy-glucopyranose. In addition, the trisaccharide beta-D-GalANGro-(1-3)-beta-D-QuiNAc-(1-4)-D-altro-hept ulose and the disaccharide alpha-D-GalANGro-(1-4)-NeuAc were isolated from acid-degraded lipopolysaccharide; the occurrence of sedoheptulose in lipopolysaccharide has not been described before. Based on the result of methylation analysis showing that galacturonic acid was the terminal sugar of the polysaccharide chain, and on the assumption that the tri- and the disaccharide represented the reducing and the non-reducing ends of the polysaccharide, respectively, the chemical structure of the O-specific chain of V. cholerae H11 is proposed as alpha-D-GalANGro-(1-4)-alpha-NeuAc-(2-3)-beta-D-GalANGro-(1- 3)-beta-D-QuiNAc- (1-[4)-alpha-D-GalANGro-(1-4)-alpha-NeuAc-(2-3)-beta-D-GalANGro -(1-3)-beta-D- QuiNAc-(1-]n-(1-4)-D-altro-heptulose. However, other possible structures can not be ruled out since the tri- and the disaccharide could be localised at different positions."} {"id": "PMID:1281099", "title": "Purification and characterization of a pore-forming protein from the marine sponge Tethya lyncurium.", "content": "A pore-forming protein was detected and purified for the first time from a marine sponge (Tethya lyncurium). The purified protein has a polypeptide molecular mass of 21 kDa and a pI of 6.4. Tethya pore-forming protein (also called Tethya hemolysin) rapidly lysed erythrocytes from a variety of organisms. After binding to target membranes, the hemolysin resisted elution with EDTA, salt or solutions of low ionic strength and hence resembled an integral membrane protein. Erythrocytes could be protected from hemolysis induced by Tethya hemolysin by addition of 30 mM dextran 4 (4-6 kDa; equivalent hydrodynamic diffusion radius, 1.75-2.3 nm) to the extracellular medium, but not by addition of uncharged molecules of smaller size [sucrose, raffinose and poly(ethylene glycol) 1550; equivalent hydrodynamic diffusion radii, 0.46, 0.57 and 1.2 nm, respectively]. This result indicates that hemolysin is able to form stable transmembrane pores with an effective diameter of about 2-3 nm. Treatment of osmotically protected erythrocytes with Tethya hemolysin caused a rapid efflux of intracellular K+ and ATP, and a rapid influx of extracellularly added Ca2+ and sucrose. In negative-staining electron microscopy, target erythrocyte membranes exposed to purified Tethya hemolysin displayed ultrastructural lesions but without visible pores.", "contents": "Purification and characterization of a pore-forming protein from the marine sponge Tethya lyncurium. A pore-forming protein was detected and purified for the first time from a marine sponge (Tethya lyncurium). The purified protein has a polypeptide molecular mass of 21 kDa and a pI of 6.4. Tethya pore-forming protein (also called Tethya hemolysin) rapidly lysed erythrocytes from a variety of organisms. After binding to target membranes, the hemolysin resisted elution with EDTA, salt or solutions of low ionic strength and hence resembled an integral membrane protein. Erythrocytes could be protected from hemolysis induced by Tethya hemolysin by addition of 30 mM dextran 4 (4-6 kDa; equivalent hydrodynamic diffusion radius, 1.75-2.3 nm) to the extracellular medium, but not by addition of uncharged molecules of smaller size [sucrose, raffinose and poly(ethylene glycol) 1550; equivalent hydrodynamic diffusion radii, 0.46, 0.57 and 1.2 nm, respectively]. This result indicates that hemolysin is able to form stable transmembrane pores with an effective diameter of about 2-3 nm. Treatment of osmotically protected erythrocytes with Tethya hemolysin caused a rapid efflux of intracellular K+ and ATP, and a rapid influx of extracellularly added Ca2+ and sucrose. In negative-staining electron microscopy, target erythrocyte membranes exposed to purified Tethya hemolysin displayed ultrastructural lesions but without visible pores."} {"id": "PMID:1281100", "title": "The alpha subunit of the stimulatory guanine-nucleotide-binding regulatory protein forms high-molecular-mass aggregates, concomitant with iloprost-induced desensitization of human platelet adenylyl cyclase.", "content": "Prolonged treatment of human platelets with the prostacyclin analog iloprost led to desensitization of the response to various prostaglandin derivatives. However, basal adenylyl cyclase activity and stimulation by agents acting directly via Gs, the stimulatory guanine-nucleotide-binding regulatory protein of adenylyl cyclase, were likewise decreased. Reconstitution of desensitized membranes with purified Gs from turkey erythrocytes indicated no alteration in the catalyst itself. However, the function of Gs (in cholate extracts) appeared to be severely impaired when reconstituted with adenylyl cyclase catalyst. Modification of Gs was also indicated by its altered sedimentation in sucrose density gradients. From Western blots, the alpha subunit of Gs, alpha s, from control platelets sedimented as a 5.6S species, while that from desensitized cells appeared at higher S values (in a polydisperse distribution). Activation by guanosine 5'-[gamma-thio]triphosphate of Gs from control platelets shifted alpha s to 3.5-3.7S, while activation of Gs from desensitized platelets induced such shift only for a minor portion of alpha s. This small fraction alone appeared to be susceptible to ADP-ribosylation by cholera toxin/[32P]NAD. Furthermore, an antibody directed against the C-terminal hexadecapeptide of alpha s precipitated much less alpha s from cholate extracts derived from desensitized platelets. Modification of alpha s during desensitization was also suggested from cross-linking experiments using the homobifunctional agent bismaleimidohexane: alpha s from desensitized platelets formed a single product of 80 kDa, while that from untreated platelets yielded a doublet (100 kDa and 110 kDa).", "contents": "The alpha subunit of the stimulatory guanine-nucleotide-binding regulatory protein forms high-molecular-mass aggregates, concomitant with iloprost-induced desensitization of human platelet adenylyl cyclase. Prolonged treatment of human platelets with the prostacyclin analog iloprost led to desensitization of the response to various prostaglandin derivatives. However, basal adenylyl cyclase activity and stimulation by agents acting directly via Gs, the stimulatory guanine-nucleotide-binding regulatory protein of adenylyl cyclase, were likewise decreased. Reconstitution of desensitized membranes with purified Gs from turkey erythrocytes indicated no alteration in the catalyst itself. However, the function of Gs (in cholate extracts) appeared to be severely impaired when reconstituted with adenylyl cyclase catalyst. Modification of Gs was also indicated by its altered sedimentation in sucrose density gradients. From Western blots, the alpha subunit of Gs, alpha s, from control platelets sedimented as a 5.6S species, while that from desensitized cells appeared at higher S values (in a polydisperse distribution). Activation by guanosine 5'-[gamma-thio]triphosphate of Gs from control platelets shifted alpha s to 3.5-3.7S, while activation of Gs from desensitized platelets induced such shift only for a minor portion of alpha s. This small fraction alone appeared to be susceptible to ADP-ribosylation by cholera toxin/[32P]NAD. Furthermore, an antibody directed against the C-terminal hexadecapeptide of alpha s precipitated much less alpha s from cholate extracts derived from desensitized platelets. Modification of alpha s during desensitization was also suggested from cross-linking experiments using the homobifunctional agent bismaleimidohexane: alpha s from desensitized platelets formed a single product of 80 kDa, while that from untreated platelets yielded a doublet (100 kDa and 110 kDa)."} {"id": "PMID:1281101", "title": "Measuring the quality of life of patients with benign prostatic hyperplasia. Assessment of the usefulness of a new quality of life questionnaire specially adapted to benign prostatic hyperplasia patients.", "content": "A questionnaire consisting of 36 questions based on a visual analogue scale for measuring the quality of life (QOL) of benign prostatic hyperplasia (BPH) patients is presented and assessed. The sensitivity of the questionnaire is demonstrated by its ability to register a statistically significant (p less than 0.01) improvement of QOL after prostate surgery (transurethral resection of the prostate). Its reliability is shown by its ability to give reproducible results in a nonoperated BPH patient group. Patient compliance has been excellent. It is discussed to what extent questions directly concerning symptoms from prostatism should be included in QOL questionnaires for BPH patients. Nonparametric statistics are applied. It is concluded that questionnaires like this are useful tools in the assessment of BPH patients, irrespective of the treatment modality. They will probably be of particular value in studies of drug therapy of BPH, complementing methods of assessment like symptom score and urodynamic parameters.", "contents": "Measuring the quality of life of patients with benign prostatic hyperplasia. Assessment of the usefulness of a new quality of life questionnaire specially adapted to benign prostatic hyperplasia patients. A questionnaire consisting of 36 questions based on a visual analogue scale for measuring the quality of life (QOL) of benign prostatic hyperplasia (BPH) patients is presented and assessed. The sensitivity of the questionnaire is demonstrated by its ability to register a statistically significant (p less than 0.01) improvement of QOL after prostate surgery (transurethral resection of the prostate). Its reliability is shown by its ability to give reproducible results in a nonoperated BPH patient group. Patient compliance has been excellent. It is discussed to what extent questions directly concerning symptoms from prostatism should be included in QOL questionnaires for BPH patients. Nonparametric statistics are applied. It is concluded that questionnaires like this are useful tools in the assessment of BPH patients, irrespective of the treatment modality. They will probably be of particular value in studies of drug therapy of BPH, complementing methods of assessment like symptom score and urodynamic parameters."} {"id": "PMID:1281102", "title": "Prostate-specific antigen and prostatic acid phosphatase in the detection of early prostate cancer and in the prediction of regional lymph node metastases.", "content": "Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed, however, by digital rectal examination. This indicates that PSA determination cannot replace digital rectal examination as a screening method for prostate cancer. In this study, it was possible neither by PSA nor by PAP to define a practicable cutoff level for patients with and without lymph node metastases. A clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible by either PSA or PAP alone.", "contents": "Prostate-specific antigen and prostatic acid phosphatase in the detection of early prostate cancer and in the prediction of regional lymph node metastases. Serum values of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were determined in 180 patients prior to pelvic lymphadenectomy and radical prostatectomy and in 40 patients prior to pelvic lymphadenectomy alone. In all tumor stages, PSA was superior to PAP in detecting cancer of the prostate. By PSA determination using a cutoff level of 4 ng/ml (Tandem assay), 28.8% of the patients with prostate cancer, stage pT2pN0M0, and 17.8% of the cases with a stage pT3pN0M0 tumor could not be detected. All these tumors had been noticed, however, by digital rectal examination. This indicates that PSA determination cannot replace digital rectal examination as a screening method for prostate cancer. In this study, it was possible neither by PSA nor by PAP to define a practicable cutoff level for patients with and without lymph node metastases. A clear differentiation between the stages pT2pN0M0 and pT3pN0M0 was not possible by either PSA or PAP alone."} {"id": "PMID:1281103", "title": "Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients.", "content": "A double-blind placebo-controlled study was performed in 35 benign prostatic hypertrophy (BPH) patients never treated before. The patients were randomized into two groups, the 1st (18 cases) receiving Serenoa repens extract (160 mg t.d.) for 3 months up to the day before the operation of transvesical adenomectomy and the 2nd (17 cases) receiving placebo. Steroid receptors were evaluated in the nuclear (n) and cytosolic (c) fraction using the saturation analysis technique (Scatchard analysis or single saturating-dose assay) for androgen (AR) and estrogen (ER) receptors and the enzyme immunoassay (EIA) for ER and progesterone receptors (PgR). Scatchard analysis of ERc and ERn revealed the presence of two classes of binding sites, one with high-affinity low-capacity binding and the other with low-affinity high-capacity binding. In the untreated BPH group, ER were higher in the n than in the c fraction: ERn were positive in 14 cases and ERc in 12 of 17 cases. In the BPH group treated with S. repens extract on the contrary, ERn were negative for both binding classes in 17 cases and ERc in 6 of 18 cases. Using EIA, ERn and ERc were detected in all 15 samples examined, but in the treated group, ERn were significantly (p less than 0.01) lower than in the untreated group, whilst ERc remained almost unchanged. Similar results were obtained measuring PgR: the n fraction of the treated group prostatic samples was significantly (p less than 0.01) lower than that of the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Evidence that Serenoa repens extract displays an antiestrogenic activity in prostatic tissue of benign prostatic hypertrophy patients. A double-blind placebo-controlled study was performed in 35 benign prostatic hypertrophy (BPH) patients never treated before. The patients were randomized into two groups, the 1st (18 cases) receiving Serenoa repens extract (160 mg t.d.) for 3 months up to the day before the operation of transvesical adenomectomy and the 2nd (17 cases) receiving placebo. Steroid receptors were evaluated in the nuclear (n) and cytosolic (c) fraction using the saturation analysis technique (Scatchard analysis or single saturating-dose assay) for androgen (AR) and estrogen (ER) receptors and the enzyme immunoassay (EIA) for ER and progesterone receptors (PgR). Scatchard analysis of ERc and ERn revealed the presence of two classes of binding sites, one with high-affinity low-capacity binding and the other with low-affinity high-capacity binding. In the untreated BPH group, ER were higher in the n than in the c fraction: ERn were positive in 14 cases and ERc in 12 of 17 cases. In the BPH group treated with S. repens extract on the contrary, ERn were negative for both binding classes in 17 cases and ERc in 6 of 18 cases. Using EIA, ERn and ERc were detected in all 15 samples examined, but in the treated group, ERn were significantly (p less than 0.01) lower than in the untreated group, whilst ERc remained almost unchanged. Similar results were obtained measuring PgR: the n fraction of the treated group prostatic samples was significantly (p less than 0.01) lower than that of the untreated group.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281104", "title": "Noradrenergic and peptidergic innervation of secondary lymphoid organs: role in experimental rheumatoid arthritis.", "content": "Noradrenergic (NA) and peptidergic nerve fibres are present in both primary and secondary lymphoid organs, distributing with the vasculature, trabecular and capsular smooth muscle, and within the parenchyma among cells of the immune system. NA nerve terminals directly abut lymphocytes and macrophages in spleen and lymph nodes. In these organs, norepinephrine has fulfilled the basic criteria for neurotransmission with cells of the immune system as targets. In vitro and in vivo studies have demonstrated NA modulation of primary and secondary antibody responses, cytotoxic T cell responses, natural killer cell activity, and proliferation and differentiation of both T and B lymphocytes. Substance P (SP) has been shown to modulate inflammatory responses, lymphocyte proliferation, and other immunologic reactivity. We investigated the role of NA and SP nerve fibres within lymph nodes in experimental allergic auto-immune arthritis in Lewis rats. Denervation of NA nerve fibres in popliteal and inguinal lymph nodes with 6-hydroxy-dopamine resulted in earlier onset and enhanced severity of arthritic changes as well as inflammation in bilaterally induced experimental arthritis, while denervation of SP nerve fibres in popliteal and inguinal lymph nodes with capsaicin resulted in delayed onset and diminished severity of the inflammatory changes ipsilaterally, and prevention of contralateral arthritic changes in unilaterally induced experimental arthritis. These findings suggest that NA and SP nerve fibres in lymph nodes can modulate the time course of onset and the severity of experimental arthritis in Lewis rats. These modulatory effects are distinctly different from the effects of NA and SP nerve fibres in the joints themselves.", "contents": "Noradrenergic and peptidergic innervation of secondary lymphoid organs: role in experimental rheumatoid arthritis. Noradrenergic (NA) and peptidergic nerve fibres are present in both primary and secondary lymphoid organs, distributing with the vasculature, trabecular and capsular smooth muscle, and within the parenchyma among cells of the immune system. NA nerve terminals directly abut lymphocytes and macrophages in spleen and lymph nodes. In these organs, norepinephrine has fulfilled the basic criteria for neurotransmission with cells of the immune system as targets. In vitro and in vivo studies have demonstrated NA modulation of primary and secondary antibody responses, cytotoxic T cell responses, natural killer cell activity, and proliferation and differentiation of both T and B lymphocytes. Substance P (SP) has been shown to modulate inflammatory responses, lymphocyte proliferation, and other immunologic reactivity. We investigated the role of NA and SP nerve fibres within lymph nodes in experimental allergic auto-immune arthritis in Lewis rats. Denervation of NA nerve fibres in popliteal and inguinal lymph nodes with 6-hydroxy-dopamine resulted in earlier onset and enhanced severity of arthritic changes as well as inflammation in bilaterally induced experimental arthritis, while denervation of SP nerve fibres in popliteal and inguinal lymph nodes with capsaicin resulted in delayed onset and diminished severity of the inflammatory changes ipsilaterally, and prevention of contralateral arthritic changes in unilaterally induced experimental arthritis. These findings suggest that NA and SP nerve fibres in lymph nodes can modulate the time course of onset and the severity of experimental arthritis in Lewis rats. These modulatory effects are distinctly different from the effects of NA and SP nerve fibres in the joints themselves."} {"id": "PMID:1281105", "title": "Role of the endothelial system in Bay K 8644 enantiomer and nifedipine vasomodulator action in rat aorta.", "content": "The potential importance of the endothelial system in regulating the effects of (-)-Bay K 8644 (0.1 microM), (+)-Bay K 8644 (0.1 microM) and nifedipine (10 nM) on resting tension, on contractile responses to noradrenaline (NA) and Ca2+ (in a Ca(2+)-free high-K+ solution), and on basal, NA-induced and K(+)-induced 45Ca2+ uptake, was investigated in rat aorta rings. Mechanical removal of endothelium considerably potentiated the contractile response induced by NA in standard medium and by Ca2+ in Ca(2+)-free high-K+ (15 mM) medium, but did not modify the response induced by Ca2+ in Ca(2+)-free high-K+ (55 mM) medium or by NA in Ca(2+)-free medium. Furthermore, the basal 45Ca2+ uptake and that induced by NA (10 microM) or KCl (15 and 55 mM) were similar in endothelium-rubbed and intact rings. (-)-Bay K 8644 (0.1 microM) shifted the NA and Ca2+ concentration-response curves to the left with potentiation of the maximal contraction. However, (+)-Bay K 8644 (0.1 microM) and nifedipine (10 nM) caused a shift to the right, with depression of the maximal contraction. The NA concentration-response curves, and those of Ca2+ in Ca(2+)-free high-K+ (55 mM) medium, were affected by the drugs to similar extents, and were not modified by the presence or absence of endothelial cells. The drugs tested did not affect resting tension. Basal 45Ca2+ uptake was not modified by either nifedipine or the Bay K 8644 enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Role of the endothelial system in Bay K 8644 enantiomer and nifedipine vasomodulator action in rat aorta. The potential importance of the endothelial system in regulating the effects of (-)-Bay K 8644 (0.1 microM), (+)-Bay K 8644 (0.1 microM) and nifedipine (10 nM) on resting tension, on contractile responses to noradrenaline (NA) and Ca2+ (in a Ca(2+)-free high-K+ solution), and on basal, NA-induced and K(+)-induced 45Ca2+ uptake, was investigated in rat aorta rings. Mechanical removal of endothelium considerably potentiated the contractile response induced by NA in standard medium and by Ca2+ in Ca(2+)-free high-K+ (15 mM) medium, but did not modify the response induced by Ca2+ in Ca(2+)-free high-K+ (55 mM) medium or by NA in Ca(2+)-free medium. Furthermore, the basal 45Ca2+ uptake and that induced by NA (10 microM) or KCl (15 and 55 mM) were similar in endothelium-rubbed and intact rings. (-)-Bay K 8644 (0.1 microM) shifted the NA and Ca2+ concentration-response curves to the left with potentiation of the maximal contraction. However, (+)-Bay K 8644 (0.1 microM) and nifedipine (10 nM) caused a shift to the right, with depression of the maximal contraction. The NA concentration-response curves, and those of Ca2+ in Ca(2+)-free high-K+ (55 mM) medium, were affected by the drugs to similar extents, and were not modified by the presence or absence of endothelial cells. The drugs tested did not affect resting tension. Basal 45Ca2+ uptake was not modified by either nifedipine or the Bay K 8644 enantiomers.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281106", "title": "Alpha 2-adrenoceptor-mediated contractions in the rabbit aorta treated with BAY K 8644.", "content": "We tested the effect of the selective alpha 2-adrenoceptor agonists B-HT 920 and B-HT 933 on the rabbit aorta. These drugs had weak contractile effects in the tissue, which were inhibited by the selective alpha 1-adrenoceptor antagonist prazosin (10(-5) M). Their contractile effects were potentiated by the Ca2+ channel facilitator BAY K 8644 (10(-6) M). The selective alpha 2-adrenoceptor antagonist yohimbine (10(-5) M) reduced the contractions elicited by B-HT 920 and B-HT 933 in the presence of BAY K 8644 (10(-6) M), but did not alter the control effect of these drugs. In the rabbit aorta, the contractile effect of B-HT 920 and B-HT 933 in the presence of BAY K 8644 (10(-6) M) was partly caused by alpha 1-adrenoceptor stimulation, because prazosin (10(-5) M) relaxed the contractions elicited under these conditions. In the aorta preincubated with BAY K 8644 (10(-6) M) and prazosin (10(-5) M), B-HT 920 (3 x 10(-4) M) elicited non-sustained phasic contractions (1-5 g), which were probably due to alpha 2-adrenoceptor stimulation, as they were inhibited by yohimbine (10(-5) M). In similar experiments B-HT 933 (3 x 10(-4) M) caused inconsistent and slight contractions (< 0.5 g developed tension).", "contents": "Alpha 2-adrenoceptor-mediated contractions in the rabbit aorta treated with BAY K 8644. We tested the effect of the selective alpha 2-adrenoceptor agonists B-HT 920 and B-HT 933 on the rabbit aorta. These drugs had weak contractile effects in the tissue, which were inhibited by the selective alpha 1-adrenoceptor antagonist prazosin (10(-5) M). Their contractile effects were potentiated by the Ca2+ channel facilitator BAY K 8644 (10(-6) M). The selective alpha 2-adrenoceptor antagonist yohimbine (10(-5) M) reduced the contractions elicited by B-HT 920 and B-HT 933 in the presence of BAY K 8644 (10(-6) M), but did not alter the control effect of these drugs. In the rabbit aorta, the contractile effect of B-HT 920 and B-HT 933 in the presence of BAY K 8644 (10(-6) M) was partly caused by alpha 1-adrenoceptor stimulation, because prazosin (10(-5) M) relaxed the contractions elicited under these conditions. In the aorta preincubated with BAY K 8644 (10(-6) M) and prazosin (10(-5) M), B-HT 920 (3 x 10(-4) M) elicited non-sustained phasic contractions (1-5 g), which were probably due to alpha 2-adrenoceptor stimulation, as they were inhibited by yohimbine (10(-5) M). In similar experiments B-HT 933 (3 x 10(-4) M) caused inconsistent and slight contractions (< 0.5 g developed tension)."} {"id": "PMID:1281107", "title": "Rat hepatocytes in primary culture synthesize and secrete cellular fibronectin.", "content": "Fibronectins, involved in cell-matrix interactions and cell attachment, are glycoproteins which show a remarkable heterogeneity, due to alternative splicing. The type III-related domains, ED-A and ED-B, are present in cellular fibronectin in a variety of ratios whereas they are absent in circulating plasma fibronectin. Fibronectin synthesis by hepatocytes which are accepted as suppliers of plasma fibronectin was studied in primary cultures during a 6-day culture period. Using site-specific antibodies we demonstrate that rat hepatocytes are also able to synthesize and secrete fibronectin bearing the ED-A domain from Day 3 on after inoculation. By immunocytological characterization of the hepatocyte monolayer with antibodies directed against desmin, laminin, collagen IV, alpha-SM-actin, or ED-1 or factor VIII-related antigen, contaminating mesenchymal hepatic cell-types as a source for cellular fibronectin production could be ruled out. Dexamethasone treatment caused enhanced fibronectin synthesis and cellular fibronectin was already detectable at Day 1 after plating. Elevation of cellular fibronectin synthesis after prolonged culture-terms and by dexamethasone could also be demonstrated on mRNA steady-state level, using ED-A cDNA as a probe in hybridization analysis. Dot blot hybridisation proved a prominent response of cellular fibronectin mRNA level to dexamethasone at Day 1 when dexamethasone treatment resulted in an increased contribution of ED-A-positive fibronectin transcripts to total fibronectin mRNA level.", "contents": "Rat hepatocytes in primary culture synthesize and secrete cellular fibronectin. Fibronectins, involved in cell-matrix interactions and cell attachment, are glycoproteins which show a remarkable heterogeneity, due to alternative splicing. The type III-related domains, ED-A and ED-B, are present in cellular fibronectin in a variety of ratios whereas they are absent in circulating plasma fibronectin. Fibronectin synthesis by hepatocytes which are accepted as suppliers of plasma fibronectin was studied in primary cultures during a 6-day culture period. Using site-specific antibodies we demonstrate that rat hepatocytes are also able to synthesize and secrete fibronectin bearing the ED-A domain from Day 3 on after inoculation. By immunocytological characterization of the hepatocyte monolayer with antibodies directed against desmin, laminin, collagen IV, alpha-SM-actin, or ED-1 or factor VIII-related antigen, contaminating mesenchymal hepatic cell-types as a source for cellular fibronectin production could be ruled out. Dexamethasone treatment caused enhanced fibronectin synthesis and cellular fibronectin was already detectable at Day 1 after plating. Elevation of cellular fibronectin synthesis after prolonged culture-terms and by dexamethasone could also be demonstrated on mRNA steady-state level, using ED-A cDNA as a probe in hybridization analysis. Dot blot hybridisation proved a prominent response of cellular fibronectin mRNA level to dexamethasone at Day 1 when dexamethasone treatment resulted in an increased contribution of ED-A-positive fibronectin transcripts to total fibronectin mRNA level."} {"id": "PMID:1281108", "title": "Synthesis of undulin by rat liver fat-storing cells: comparison with fibronectin and tenascin.", "content": "Fat-storing cells (FSCs) are known to synthesize various components of the hepatic extracellular matrix and thereby play an important role during liver fibrogenesis. The aim of our study was to investigate the synthesis of undulin, a recently described connective tissue protein belonging to the fibronectin-tenascin superfamily of glycoproteins, by fat-storing cells in primary culture. SDS-PAGE analysis of immunoprecipitates from cell layer lysates or media pulse-labeled with radioactive methionine revealed undulin-specific bands A (270 kDa), B1 (190 kDa), and B2 (180 kDa) after reduction. A single undulin-specific transcript was detected at about 7 kb. Undulin synthesized by cell-free translation revealed two polypeptides migrating about 5000 Da below the B1 and B2 subunits. Treatment of FSCs with tunicamycin created two novel bands slightly below the B2 chain. Since the electrophoretic patterns of undulin chains recovered by cell-free translation and tunicamycin treatment of cells were very similar we suggest that N-glycosylation is the major post-translational processing event. Newly synthesized undulin was detected after 30 min of pulse labeling in the cell layer fraction and was secreted into the medium at a slower rate than fibronectin. In contrast to fibronectin and tenascin, undulin was already synthesized by freshly isolated FSCs and during the early stage of primary FSC culture (\"resting\" cells), supporting the hypothesis that undulin is associated with a differentiated mesenchyma. However, in analogy to fibronectin and tenascin, undulin was also synthesized by \"activated\" FSCs, indicating that undulin might also be of importance in dedifferentiated tissues.", "contents": "Synthesis of undulin by rat liver fat-storing cells: comparison with fibronectin and tenascin. Fat-storing cells (FSCs) are known to synthesize various components of the hepatic extracellular matrix and thereby play an important role during liver fibrogenesis. The aim of our study was to investigate the synthesis of undulin, a recently described connective tissue protein belonging to the fibronectin-tenascin superfamily of glycoproteins, by fat-storing cells in primary culture. SDS-PAGE analysis of immunoprecipitates from cell layer lysates or media pulse-labeled with radioactive methionine revealed undulin-specific bands A (270 kDa), B1 (190 kDa), and B2 (180 kDa) after reduction. A single undulin-specific transcript was detected at about 7 kb. Undulin synthesized by cell-free translation revealed two polypeptides migrating about 5000 Da below the B1 and B2 subunits. Treatment of FSCs with tunicamycin created two novel bands slightly below the B2 chain. Since the electrophoretic patterns of undulin chains recovered by cell-free translation and tunicamycin treatment of cells were very similar we suggest that N-glycosylation is the major post-translational processing event. Newly synthesized undulin was detected after 30 min of pulse labeling in the cell layer fraction and was secreted into the medium at a slower rate than fibronectin. In contrast to fibronectin and tenascin, undulin was already synthesized by freshly isolated FSCs and during the early stage of primary FSC culture (\"resting\" cells), supporting the hypothesis that undulin is associated with a differentiated mesenchyma. However, in analogy to fibronectin and tenascin, undulin was also synthesized by \"activated\" FSCs, indicating that undulin might also be of importance in dedifferentiated tissues."} {"id": "PMID:1281109", "title": "A role of retinoic acid in the regulation of the morphology and the levels of intermediate filament proteins and mRNAs in PC12 cells.", "content": "An adrenal tumor-derived cell line (PC12W) cultured in the presence of nerve growth factor exhibited a spindle-shaped cell morphology resembling neuronal cells. The shape of these cells can be specifically changed in vitamin A-depleted medium supplemented with retinoic acid. Retinoic acid promoted an epithelial-like cell morphology except for occasional neuronal processes. These morphological results were correlated with differential expression of intermediate filaments at the mRNA and protein levels in these cells. Retinoic acid suppressed the synthesis of peripherin, an intermediate filament protein predominantly found in peripheral nerve cells, but a high level of simple keratins, normally found in simple epithelial cells, was present in retinoic acid-treated PC12 cells. The neurofilaments typically expressed in neurons remained virtually unaffected under the same conditions. In contrast, nerve growth factor induced the production of neurofilaments, but suppressed the synthesis of simple keratins. Since intermediate filament expression is known to be tissue-specific, these changes in expression together with the cell morphology changes are consistent with PC12 cells undergoing an epithelial-like differentiation in the presence of retinoic acid and a neuronal-like differentiation in the presence of nerve growth factor. These results suggest that retinoic acid and nerve growth factor are both effective regulators of PC12 cell differentiation but stimulate opposing pathways.", "contents": "A role of retinoic acid in the regulation of the morphology and the levels of intermediate filament proteins and mRNAs in PC12 cells. An adrenal tumor-derived cell line (PC12W) cultured in the presence of nerve growth factor exhibited a spindle-shaped cell morphology resembling neuronal cells. The shape of these cells can be specifically changed in vitamin A-depleted medium supplemented with retinoic acid. Retinoic acid promoted an epithelial-like cell morphology except for occasional neuronal processes. These morphological results were correlated with differential expression of intermediate filaments at the mRNA and protein levels in these cells. Retinoic acid suppressed the synthesis of peripherin, an intermediate filament protein predominantly found in peripheral nerve cells, but a high level of simple keratins, normally found in simple epithelial cells, was present in retinoic acid-treated PC12 cells. The neurofilaments typically expressed in neurons remained virtually unaffected under the same conditions. In contrast, nerve growth factor induced the production of neurofilaments, but suppressed the synthesis of simple keratins. Since intermediate filament expression is known to be tissue-specific, these changes in expression together with the cell morphology changes are consistent with PC12 cells undergoing an epithelial-like differentiation in the presence of retinoic acid and a neuronal-like differentiation in the presence of nerve growth factor. These results suggest that retinoic acid and nerve growth factor are both effective regulators of PC12 cell differentiation but stimulate opposing pathways."} {"id": "PMID:1281110", "title": "Expression of decorin by sprouting bovine aortic endothelial cells exhibiting angiogenesis in vitro.", "content": "In our recent studies, we have demonstrated that monolayer cultures of bovine aortic endothelial (BAE) cells that do not express type I collagen also fail to express and synthesize decorin, a small chondroitin/dermatan sulfate proteoglycan that interacts with type I collagen and regulates collagen fibrillogenesis in vitro. However, BAE cells exhibiting a spontaneous sprouting phenotype and a predisposition toward the formation of cords and tube-like structures (an in vitro model for angiogenesis) initiate the synthesis of type I collagen during their morphological transition from a polygonal monolayer to an angiogenic phenotype. In the present study, we examined whether BAE cells also initiate the synthesis of the proteoglycan decorin during this morphological transition. We show by Northern blot analysis and by immunochemical methods that BAE cell cultures containing sprouting cells and cords, but not monolayer cultures of these cells, express and synthesize decorin (M(r) approximately 100,000). We also show that type I collagen expression by BAE cell cultures is initiated concomitantly. However, the localization of decorin and type I collagen in cord and tube-forming BAE cell cultures is not completely identical. Type I collagen is detected only in sprouting BAE cells and in endothelial cords, whereas decorin is also apparent in BAE cells surrounding the cords and tubes. Our results indicate that the synthesis of decorin as well as type I collagen is associated with endothelial cord and tube formation in vitro.", "contents": "Expression of decorin by sprouting bovine aortic endothelial cells exhibiting angiogenesis in vitro. In our recent studies, we have demonstrated that monolayer cultures of bovine aortic endothelial (BAE) cells that do not express type I collagen also fail to express and synthesize decorin, a small chondroitin/dermatan sulfate proteoglycan that interacts with type I collagen and regulates collagen fibrillogenesis in vitro. However, BAE cells exhibiting a spontaneous sprouting phenotype and a predisposition toward the formation of cords and tube-like structures (an in vitro model for angiogenesis) initiate the synthesis of type I collagen during their morphological transition from a polygonal monolayer to an angiogenic phenotype. In the present study, we examined whether BAE cells also initiate the synthesis of the proteoglycan decorin during this morphological transition. We show by Northern blot analysis and by immunochemical methods that BAE cell cultures containing sprouting cells and cords, but not monolayer cultures of these cells, express and synthesize decorin (M(r) approximately 100,000). We also show that type I collagen expression by BAE cell cultures is initiated concomitantly. However, the localization of decorin and type I collagen in cord and tube-forming BAE cell cultures is not completely identical. Type I collagen is detected only in sprouting BAE cells and in endothelial cords, whereas decorin is also apparent in BAE cells surrounding the cords and tubes. Our results indicate that the synthesis of decorin as well as type I collagen is associated with endothelial cord and tube formation in vitro."} {"id": "PMID:1281111", "title": "An in vitro model of rodent nongenotoxic hepatocarcinogenesis.", "content": "An in vitro model of liver in which rat hepatocytes are maintained as cocultures with nonparenchymal epithelial cells (NPC) derived from liver has been developed and characterized with respect to maintenance of hepatocyte viability and differentiated function. The system was then evaluated as a model for studying peroxisome proliferator-induced rodent liver nongenotoxic carcinogenesis. Within the coculture model, hepatocyte viability and morphology were maintained for 1 month or more within a system that is both easily accessible for microscopic examination and is free of any additives that may lead to artifacts. Even after 1 month or more, hepatocyte cocultures retained expression of the constitutive liver marker albumin. In addition, they maintained the ability to show induction of the peroxisome proliferator-inducible enzymes peroxisomal bifunctional enzyme (PBE) and cytochrome P450IVA1 in response to the peroxisome proliferator nafenopin. After 4 weeks, NPC cocultures showed a six- and a fourfold induction of PBE and cytochrome P450IVA1 expression, respectively, which compared well with the three- and fivefold induction seen in freshly isolated cells. This was paralleled by an increase in the cytoplasmic volume fraction of peroxisomes averaging eightfold. Interestingly, great heterogeneity was exhibited between adjacent hepatocytes in terms of the degree of peroxisome proliferation, a finding reflected by immunocytochemical staining which indicated heterogeneity in the level of expression of the peroxisome proliferator-inducible enzymes. Other cell lines representing different tissue types, morphologies, and species were also examined for their ability to support hepatocyte survival but were found to be ineffective, with the exception of a bovine corneal endothelial cell line. This line supported hepatocyte survival and maintenance of differentiated function but to a lesser extent than that observed with NPC. Ultrastructural examination of NPC cocultures revealed extensive interhepatocyte junctional complexes and interdigitation of adjacent membranes together with the presence of bile canalicular structures. There were no junctional complexes between the hepatocytes and the supporting feeder cells with any contact being limited to a close association of the hepatocytes with the extracellular matrix presumably produced by the NPC. The data demonstrate that hepatocytes maintained in vitro within an NPC coculture system retain differentiated function and the ability to respond to the peroxisome proliferator class of nongenotoxic carcinogens. Cocultures will provide us with a model system for the study of changes in hepatocyte growth regulation during rodent liver nongenotoxic carcinogenesis.", "contents": "An in vitro model of rodent nongenotoxic hepatocarcinogenesis. An in vitro model of liver in which rat hepatocytes are maintained as cocultures with nonparenchymal epithelial cells (NPC) derived from liver has been developed and characterized with respect to maintenance of hepatocyte viability and differentiated function. The system was then evaluated as a model for studying peroxisome proliferator-induced rodent liver nongenotoxic carcinogenesis. Within the coculture model, hepatocyte viability and morphology were maintained for 1 month or more within a system that is both easily accessible for microscopic examination and is free of any additives that may lead to artifacts. Even after 1 month or more, hepatocyte cocultures retained expression of the constitutive liver marker albumin. In addition, they maintained the ability to show induction of the peroxisome proliferator-inducible enzymes peroxisomal bifunctional enzyme (PBE) and cytochrome P450IVA1 in response to the peroxisome proliferator nafenopin. After 4 weeks, NPC cocultures showed a six- and a fourfold induction of PBE and cytochrome P450IVA1 expression, respectively, which compared well with the three- and fivefold induction seen in freshly isolated cells. This was paralleled by an increase in the cytoplasmic volume fraction of peroxisomes averaging eightfold. Interestingly, great heterogeneity was exhibited between adjacent hepatocytes in terms of the degree of peroxisome proliferation, a finding reflected by immunocytochemical staining which indicated heterogeneity in the level of expression of the peroxisome proliferator-inducible enzymes. Other cell lines representing different tissue types, morphologies, and species were also examined for their ability to support hepatocyte survival but were found to be ineffective, with the exception of a bovine corneal endothelial cell line. This line supported hepatocyte survival and maintenance of differentiated function but to a lesser extent than that observed with NPC. Ultrastructural examination of NPC cocultures revealed extensive interhepatocyte junctional complexes and interdigitation of adjacent membranes together with the presence of bile canalicular structures. There were no junctional complexes between the hepatocytes and the supporting feeder cells with any contact being limited to a close association of the hepatocytes with the extracellular matrix presumably produced by the NPC. The data demonstrate that hepatocytes maintained in vitro within an NPC coculture system retain differentiated function and the ability to respond to the peroxisome proliferator class of nongenotoxic carcinogens. Cocultures will provide us with a model system for the study of changes in hepatocyte growth regulation during rodent liver nongenotoxic carcinogenesis."} {"id": "PMID:1281112", "title": "Induction of alpha v beta 3 integrin-mediated attachment to extracellular matrix in beta 1 integrin (CD29)-negative B cell lines.", "content": "beta 1 integrin containing complexes have been implicated as the primary adhesion structures in many lymphocyte extracellular matrix (ECM) interactions. However, many B lymphocytes lack surface expression of the beta 1 subunit, implying that this subpopulation of lymphoid cells must employ alternate adhesion structures if they are to maintain an interactive capacity with ECM. An examination of the adherence properties of the beta 1 integrin-negative B cell line JY indicated that these cells exhibit little or no basal adherence to any of the ECM components examined. However, these cells could be induced to adhere to the ECM components fibronectin, laminin, and vitronectin following treatment with PMA. Blocking studies with monoclonal antibodies indicated the alpha v beta 3 integrin complex was involved in the attachment to each of these ligands. However, the adherence to fibronectin displayed a complex pattern of inhibition suggesting the involvement of other ECM receptors. The utilization of the alpha v beta 3 complex was not unique to the JY cell line. Other B cell lines were observed to employ alpha v beta 3, and these lines similarly lacked expression of beta 1 integrin. These results indicate that alpha v beta 3 can act as a lymphoid ECM-adhesion structure which may provide an alternative means for lymphocytes to interact with ECM. Furthermore, these studies provide evidence for the presence of lymphoid-associated alpha v beta 3 integrins with regulatable activity, which contrasts with the constitutive adhesive potential of these complexes when present on other cell types.", "contents": "Induction of alpha v beta 3 integrin-mediated attachment to extracellular matrix in beta 1 integrin (CD29)-negative B cell lines. beta 1 integrin containing complexes have been implicated as the primary adhesion structures in many lymphocyte extracellular matrix (ECM) interactions. However, many B lymphocytes lack surface expression of the beta 1 subunit, implying that this subpopulation of lymphoid cells must employ alternate adhesion structures if they are to maintain an interactive capacity with ECM. An examination of the adherence properties of the beta 1 integrin-negative B cell line JY indicated that these cells exhibit little or no basal adherence to any of the ECM components examined. However, these cells could be induced to adhere to the ECM components fibronectin, laminin, and vitronectin following treatment with PMA. Blocking studies with monoclonal antibodies indicated the alpha v beta 3 integrin complex was involved in the attachment to each of these ligands. However, the adherence to fibronectin displayed a complex pattern of inhibition suggesting the involvement of other ECM receptors. The utilization of the alpha v beta 3 complex was not unique to the JY cell line. Other B cell lines were observed to employ alpha v beta 3, and these lines similarly lacked expression of beta 1 integrin. These results indicate that alpha v beta 3 can act as a lymphoid ECM-adhesion structure which may provide an alternative means for lymphocytes to interact with ECM. Furthermore, these studies provide evidence for the presence of lymphoid-associated alpha v beta 3 integrins with regulatable activity, which contrasts with the constitutive adhesive potential of these complexes when present on other cell types."} {"id": "PMID:1281113", "title": "Induction of nuclear lamins A/C during in vitro-induced differentiation of F9 and P19 embryonal carcinoma cells.", "content": "Lamin B is the major constituent of the nuclear lamina of undifferentiated mouse embryonal carcinoma cells. The full complement of the three major lamins A, B, and C, found in somatic mammalian cells, is acquired after induction of differentiation in vitro by certain drugs. In this study we have examined the time course of lamin A/C expression in the two embryonal carcinoma cell lines F9 and P19. We show here that lamins A/C are detectable in these cell lines, at the mRNA level and at the protein level, after 3 days of growth in media containing retinoic acid or retinoic acid + 3-isobutyl-1-methylxanthine. The data reported here indicate that the expression of lamins A/C is mainly regulated at the transcriptional level and occurs when the cells, by morphological and functional criteria, have differentiated along their developmental pathway.", "contents": "Induction of nuclear lamins A/C during in vitro-induced differentiation of F9 and P19 embryonal carcinoma cells. Lamin B is the major constituent of the nuclear lamina of undifferentiated mouse embryonal carcinoma cells. The full complement of the three major lamins A, B, and C, found in somatic mammalian cells, is acquired after induction of differentiation in vitro by certain drugs. In this study we have examined the time course of lamin A/C expression in the two embryonal carcinoma cell lines F9 and P19. We show here that lamins A/C are detectable in these cell lines, at the mRNA level and at the protein level, after 3 days of growth in media containing retinoic acid or retinoic acid + 3-isobutyl-1-methylxanthine. The data reported here indicate that the expression of lamins A/C is mainly regulated at the transcriptional level and occurs when the cells, by morphological and functional criteria, have differentiated along their developmental pathway."} {"id": "PMID:1281116", "title": "Irreversible oxidative inactivation of protein kinase C by photosensitive inhibitor calphostin C.", "content": "Isolated protein kinase C (PKC) was irreversibly inactivated by a brief (min) incubation with calphostin C in the presence of light. This inactivation required Ca2+ either in a millimolar range in the absence of lipid activators or in a submicromolar range in the presence of lipid activators. In addition, an oxygen atmosphere was required suggesting the involvement of oxidation(s) in this inactivation process. Furthermore, PKC inactivation might involve a site-specific oxidative modification of the enzyme at the Ca(2+)-induced hydrophobic region. Physical quenchers of singlet oxygen such as lycopene, beta-carotene, and alpha-tocopherol all reduced the calphostin C-induced inactivation of PKC. In intact cells treated with calphostin C, the inactivation of PKC was rapid in the membrane fraction compared to cytosol. This intracellular PKC inactivation was also found to be irreversible. Therefore, calphostin C can bring prolonged effects for several hours in cells treated for a short time. Taken together these results suggest that the calphostin C-mediated inactivation of PKC involves a site-specific and a 'cage' type oxidative modification of PKC.", "contents": "Irreversible oxidative inactivation of protein kinase C by photosensitive inhibitor calphostin C. Isolated protein kinase C (PKC) was irreversibly inactivated by a brief (min) incubation with calphostin C in the presence of light. This inactivation required Ca2+ either in a millimolar range in the absence of lipid activators or in a submicromolar range in the presence of lipid activators. In addition, an oxygen atmosphere was required suggesting the involvement of oxidation(s) in this inactivation process. Furthermore, PKC inactivation might involve a site-specific oxidative modification of the enzyme at the Ca(2+)-induced hydrophobic region. Physical quenchers of singlet oxygen such as lycopene, beta-carotene, and alpha-tocopherol all reduced the calphostin C-induced inactivation of PKC. In intact cells treated with calphostin C, the inactivation of PKC was rapid in the membrane fraction compared to cytosol. This intracellular PKC inactivation was also found to be irreversible. Therefore, calphostin C can bring prolonged effects for several hours in cells treated for a short time. Taken together these results suggest that the calphostin C-mediated inactivation of PKC involves a site-specific and a 'cage' type oxidative modification of PKC."} {"id": "PMID:1281117", "title": "Sperm nuclear chromatin normality: relationship with sperm morphology, sperm-zona pellucida binding, and fertilization rates in vitro.", "content": "To study whether the results of tests of sperm chromatin and deoxyribonucleic acid (DNA) normality are related to fertilization rates in vitro. Normal morphology, nuclear maturity determined by acidic aniline blue stain, and DNA normality determined by acridine orange fluorescence of sperm in insemination medium and the number of sperm bound to the zona pellucida (ZP) of the oocytes that had failed to fertilize in vitro were determined. The relationship between sperm test results and fertilization rates were analyzed by logistic regression. Samples were obtained from patients undergoing in vitro fertilization (IVF) treatment. The number of sperm bound to the ZP, the percentage of sperm with normal morphology, and the percentage of sperm with normal DNA were the most significant factors related to fertilization rates in vitro. In patients with normal morphology > or = 15% or with > 10 sperm bound per ZP, the percentage of sperm with normal DNA, the number of sperm bound to the ZP, and motility grade were significantly related to IVF rates. In patients with normal morphology > or = 15%, failure of fertilization may be because of defects of sperm-ZP binding or abnormal DNA. Assessment of DNA normality of motile sperm in the insemination medium may aid prediction of fertilization rates in addition to normal morphology and sperm-ZP binding.", "contents": "Sperm nuclear chromatin normality: relationship with sperm morphology, sperm-zona pellucida binding, and fertilization rates in vitro. To study whether the results of tests of sperm chromatin and deoxyribonucleic acid (DNA) normality are related to fertilization rates in vitro. Normal morphology, nuclear maturity determined by acidic aniline blue stain, and DNA normality determined by acridine orange fluorescence of sperm in insemination medium and the number of sperm bound to the zona pellucida (ZP) of the oocytes that had failed to fertilize in vitro were determined. The relationship between sperm test results and fertilization rates were analyzed by logistic regression. Samples were obtained from patients undergoing in vitro fertilization (IVF) treatment. The number of sperm bound to the ZP, the percentage of sperm with normal morphology, and the percentage of sperm with normal DNA were the most significant factors related to fertilization rates in vitro. In patients with normal morphology > or = 15% or with > 10 sperm bound per ZP, the percentage of sperm with normal DNA, the number of sperm bound to the ZP, and motility grade were significantly related to IVF rates. In patients with normal morphology > or = 15%, failure of fertilization may be because of defects of sperm-ZP binding or abnormal DNA. Assessment of DNA normality of motile sperm in the insemination medium may aid prediction of fertilization rates in addition to normal morphology and sperm-ZP binding."} {"id": "PMID:1281118", "title": "Treatment of interstitial pregnancy with methotrexate via hysteroscopy.", "content": "We present a case in which treatment of interstitial pregnancy with local MTX administration was performed successfully through hysteroscopic vision, without the need to operate. Decreased gestational sac dimension and increased or low beta-hCG level ( < 1,400 mIU/mL) facilitates the success rate. The follow-up showed disappearance of the gestational sac and decrease of beta-hCG levels to < 10 mIU/mL. We conclude that local MTX administration via hysteroscopy after tubal ostium visualization is feasible. The procedure should be considered in women during the reproductive age, especially in rare cases of interstitial pregnancy.", "contents": "Treatment of interstitial pregnancy with methotrexate via hysteroscopy. We present a case in which treatment of interstitial pregnancy with local MTX administration was performed successfully through hysteroscopic vision, without the need to operate. Decreased gestational sac dimension and increased or low beta-hCG level ( < 1,400 mIU/mL) facilitates the success rate. The follow-up showed disappearance of the gestational sac and decrease of beta-hCG levels to < 10 mIU/mL. We conclude that local MTX administration via hysteroscopy after tubal ostium visualization is feasible. The procedure should be considered in women during the reproductive age, especially in rare cases of interstitial pregnancy."} {"id": "PMID:1281119", "title": "The evaluation of various culture media in combination with dimethylsulfoxide for ultrarapid freezing of murine embryos.", "content": "Bicarbonate-buffered HTF medium, Medicult, and T6 are as effective as PB1 medium when used in combination with DMSO in ultrarapid freezing of two-cell mouse embryos. However, the use of phosphate-buffered T6 results in reduced in vitro development and inner cell mass size as compared with bicarbonate- and Hepes-buffered T6 when used with 3.5 M of DMSO. Hence, the use of this media for ultrarapid freezing should be avoided when this concentration of DMSO is used.", "contents": "The evaluation of various culture media in combination with dimethylsulfoxide for ultrarapid freezing of murine embryos. Bicarbonate-buffered HTF medium, Medicult, and T6 are as effective as PB1 medium when used in combination with DMSO in ultrarapid freezing of two-cell mouse embryos. However, the use of phosphate-buffered T6 results in reduced in vitro development and inner cell mass size as compared with bicarbonate- and Hepes-buffered T6 when used with 3.5 M of DMSO. Hence, the use of this media for ultrarapid freezing should be avoided when this concentration of DMSO is used."} {"id": "PMID:1281121", "title": "[Serum growth hormone binding protein (GHBP) and insulin-like growth factor binding protein (IGFBP)].", "content": "Insulin--like growth factors bind to specific binding proteins (IGFBPs) in serum and tissues. At present, six different IGFBPs have been characterized. Recent studies suggest that IGFBPs act as a reservoir for IGFs but also modulate the bioavailability of IGFs. Binding protein for growth hormone (GH) in serum has been recognized recently. Interestingly, the high affinity GH binding protein (GHBP) is identical with the extracellular domain of GH receptor and is absent in patients with Laron-type dwarfism, suggesting that serum GHBP might serve as a marker for the GH receptor in tissue. In this short review, updated information on serum GHBP and IGFBP is presented.", "contents": "[Serum growth hormone binding protein (GHBP) and insulin-like growth factor binding protein (IGFBP)]. Insulin--like growth factors bind to specific binding proteins (IGFBPs) in serum and tissues. At present, six different IGFBPs have been characterized. Recent studies suggest that IGFBPs act as a reservoir for IGFs but also modulate the bioavailability of IGFs. Binding protein for growth hormone (GH) in serum has been recognized recently. Interestingly, the high affinity GH binding protein (GHBP) is identical with the extracellular domain of GH receptor and is absent in patients with Laron-type dwarfism, suggesting that serum GHBP might serve as a marker for the GH receptor in tissue. In this short review, updated information on serum GHBP and IGFBP is presented."} {"id": "PMID:1281122", "title": "[Change in serum G-CSF levels in patients with Graves' disease by treatment with methimazole].", "content": "We evaluated the determination of serum G-CSF in the diagnosis of granulocytopenia due to methimazole (MMI) in 54 patients with Graves' disease, while they were being treated with MMI, by way of measuring WBC counts and serum levels of G-CSF, thyroid hormones, IgE, and interleukin-2. Serum TSH was measured by immunoradiometric assay, serum G-CSF was done by enzyme immunoassay, thyroid hormones and IgE were done by radioimmunoassay, and serum Interleukin-2 was done by enzyme-linked immunosorbent assay. The population whose G-CSF levels were higher than the minimum detectable level (30pg/ml) was 6 (30%) in normal subjects, 4 (22%) in patients with untreated Graves' disease, 2 (12%) in patients with treated euthyroid Graves' disease, 3 (23%) in patients with Graves' disease who had gone through agranulocytosis, and 2 (33%) in patients with Graves' disease complicated with granulocytopenia. There was no significant change in WBC counts for 4 weeks, but there was a significant difference between WBC counts before treatment and those at 8 weeks after treatment. We observed no significant change of serum G-CSF levels in patients with Graves' disease under treatment. However, there were significantly high levels of serum G-CSF and significantly low counts of WBC in patients with Graves' disease complicated with granulocytopenia induced by MMI, compared with those in normal subjects, patients with untreated Graves' disease, patients with treated euthyroid Graves' disease, and patients with euthyroid Graves' disease who had gone through agranulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Change in serum G-CSF levels in patients with Graves' disease by treatment with methimazole]. We evaluated the determination of serum G-CSF in the diagnosis of granulocytopenia due to methimazole (MMI) in 54 patients with Graves' disease, while they were being treated with MMI, by way of measuring WBC counts and serum levels of G-CSF, thyroid hormones, IgE, and interleukin-2. Serum TSH was measured by immunoradiometric assay, serum G-CSF was done by enzyme immunoassay, thyroid hormones and IgE were done by radioimmunoassay, and serum Interleukin-2 was done by enzyme-linked immunosorbent assay. The population whose G-CSF levels were higher than the minimum detectable level (30pg/ml) was 6 (30%) in normal subjects, 4 (22%) in patients with untreated Graves' disease, 2 (12%) in patients with treated euthyroid Graves' disease, 3 (23%) in patients with Graves' disease who had gone through agranulocytosis, and 2 (33%) in patients with Graves' disease complicated with granulocytopenia. There was no significant change in WBC counts for 4 weeks, but there was a significant difference between WBC counts before treatment and those at 8 weeks after treatment. We observed no significant change of serum G-CSF levels in patients with Graves' disease under treatment. However, there were significantly high levels of serum G-CSF and significantly low counts of WBC in patients with Graves' disease complicated with granulocytopenia induced by MMI, compared with those in normal subjects, patients with untreated Graves' disease, patients with treated euthyroid Graves' disease, and patients with euthyroid Graves' disease who had gone through agranulocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281123", "title": "Prostacyclin rather than nitric oxide lowers human umbilical artery tone in vitro.", "content": "This study was designed to determine vasodilator activities of two endothelium-derived relaxing factors: prostacyclin (PGI2) and nitric oxide (NO) in human umbilical arteries. Isolated vessel segments were contracted by submaximal concentrations of serotonin and bradykinin. These contractions were enhanced after inhibition of prostaglandin formation by the cyclooxygenase inhibitor indomethacin and after removal of the endothelium, both resulting in a pronounced decrease in PGI2 formation. Contractions remained unchanged after treatment of the vessels with nitro-L-arginine, a selective inhibitor of endogenous NO biosynthesis. The efficacy of inhibition of NO biosynthesis was established by a more than 60% reduction in cyclic GMP accumulation. Even inhibition of stimulated NO formation by histamine did not change vascular tone. These data suggest that PGI2 rather than NO is an endothelium-derived relaxing factor in human umbilical arteries.", "contents": "Prostacyclin rather than nitric oxide lowers human umbilical artery tone in vitro. This study was designed to determine vasodilator activities of two endothelium-derived relaxing factors: prostacyclin (PGI2) and nitric oxide (NO) in human umbilical arteries. Isolated vessel segments were contracted by submaximal concentrations of serotonin and bradykinin. These contractions were enhanced after inhibition of prostaglandin formation by the cyclooxygenase inhibitor indomethacin and after removal of the endothelium, both resulting in a pronounced decrease in PGI2 formation. Contractions remained unchanged after treatment of the vessels with nitro-L-arginine, a selective inhibitor of endogenous NO biosynthesis. The efficacy of inhibition of NO biosynthesis was established by a more than 60% reduction in cyclic GMP accumulation. Even inhibition of stimulated NO formation by histamine did not change vascular tone. These data suggest that PGI2 rather than NO is an endothelium-derived relaxing factor in human umbilical arteries."} {"id": "PMID:1281124", "title": "Galanin in sensory neurons in the spinal cord.", "content": "The distribution and physiological effects of the neuropeptide galanin (GAL) have been examined in the somatosensory system. GAL is normally present in a few sensory neurons that terminate in the dorsal horn of the spinal cord and it is colocalized with substance P and calcitonin gene-related peptide. After peripheral nerve section, but not dorsal root section, the amount of GAL produced and present in sensory fibers proximal to the section is dramatically upregulated. In parallel functional studies, we could demonstrate that exogenous GAL has a complex effect on the spinal cord reflex excitability, facilitatory at low doses and inhibitory at high doses. Furthermore, GAL inhibits the effect of excitatory neuropeptides physiologically released at the peripheral and central terminals of small diameter afferents that subserve a nociceptive function. After axotomy, the inhibitory effect of GAL is increased. We conclude that GAL may have an important role in the control of nervous impulses that underlie pain states that can occur after peripheral nerve injury.", "contents": "Galanin in sensory neurons in the spinal cord. The distribution and physiological effects of the neuropeptide galanin (GAL) have been examined in the somatosensory system. GAL is normally present in a few sensory neurons that terminate in the dorsal horn of the spinal cord and it is colocalized with substance P and calcitonin gene-related peptide. After peripheral nerve section, but not dorsal root section, the amount of GAL produced and present in sensory fibers proximal to the section is dramatically upregulated. In parallel functional studies, we could demonstrate that exogenous GAL has a complex effect on the spinal cord reflex excitability, facilitatory at low doses and inhibitory at high doses. Furthermore, GAL inhibits the effect of excitatory neuropeptides physiologically released at the peripheral and central terminals of small diameter afferents that subserve a nociceptive function. After axotomy, the inhibitory effect of GAL is increased. We conclude that GAL may have an important role in the control of nervous impulses that underlie pain states that can occur after peripheral nerve injury."} {"id": "PMID:1281125", "title": "Differential stability of mRNAs coding for alpha and gonadotropin beta subunits in cultured rat pituitary cells.", "content": "Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) result from the assembly of a common subunit alpha and a unique subunit beta, expressed in the same cell by single, structurally-related genes. In order to compare the intrinsic stability of the alpha, LH beta and FSH beta mRNA transcripts, we used cultured rat pituitary cells incubated in presence of actinomycin D. Hybridization with 32P-labelled rat cDNA probes showed that the cell content of all three mRNAs decreased with time, but at different rates. Apparent half-lives, estimated as the time necessary to observe a 50% mRNA decay, were 1.0 +/- 0.13 h for FSH beta, 6.5 +/- 0.25 h for alpha and 44 +/- 0.5 h for LH beta, stability thus exhibiting an inverse relation to the sizes of the corresponding mRNAs (approximately 1700, 800 and 700 nucleotides, respectively). Northern analysis revealed that the decline in mRNA abundance was associated with a progressive decrease in the length of mRNAs, most clearly visible for alpha and LH beta. For the most stable LH beta mRNA, shortening was apparent as early as 2 h after exposure to actinomycin D thus preceding neatly the decrease in amount starting at about 10-12 h. In vitro RNase H digestion demonstrated that shortening resulted from a reduction of the length of the poly(A) tract. These data establish that the three mRNAs coding for gonadotropin subunits have different stabilities although they share substantial homology. Diversity in size and sequence essentially resides in untranslated regions in which, we suggest, specific motifs and protein factors may interact to determine mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Differential stability of mRNAs coding for alpha and gonadotropin beta subunits in cultured rat pituitary cells. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) result from the assembly of a common subunit alpha and a unique subunit beta, expressed in the same cell by single, structurally-related genes. In order to compare the intrinsic stability of the alpha, LH beta and FSH beta mRNA transcripts, we used cultured rat pituitary cells incubated in presence of actinomycin D. Hybridization with 32P-labelled rat cDNA probes showed that the cell content of all three mRNAs decreased with time, but at different rates. Apparent half-lives, estimated as the time necessary to observe a 50% mRNA decay, were 1.0 +/- 0.13 h for FSH beta, 6.5 +/- 0.25 h for alpha and 44 +/- 0.5 h for LH beta, stability thus exhibiting an inverse relation to the sizes of the corresponding mRNAs (approximately 1700, 800 and 700 nucleotides, respectively). Northern analysis revealed that the decline in mRNA abundance was associated with a progressive decrease in the length of mRNAs, most clearly visible for alpha and LH beta. For the most stable LH beta mRNA, shortening was apparent as early as 2 h after exposure to actinomycin D thus preceding neatly the decrease in amount starting at about 10-12 h. In vitro RNase H digestion demonstrated that shortening resulted from a reduction of the length of the poly(A) tract. These data establish that the three mRNAs coding for gonadotropin subunits have different stabilities although they share substantial homology. Diversity in size and sequence essentially resides in untranslated regions in which, we suggest, specific motifs and protein factors may interact to determine mRNA stability.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281126", "title": "Tyrosine iodination and iodotyrosyl coupling of the N-terminal thyroid hormone forming site of human thyroglobulin modulate its binding to auto- and monoclonal antibodies.", "content": "The present work was aimed at studying the interaction of autoantibodies (aAb) and monoclonal antibodies (mAb) with the N-terminal thyroid hormone forming site of human thyroglobulin (TG). Obtained by CNBr treatment of TG, the peptide (22 kDa) containing the complete major hormonogenic site of human TG was purified in three forms according to the degree of iodination and iodotyrosine coupling: the native, poorly iodinated form (n-22K), the iodinated form containing iodotyrosine but not hormone residues (i-22K) and the form containing thyroid hormone (t-22K). We report that aAb from some patients with autoimmune thyroid diseases showed significant binding to both iodinated 22 kDa forms. Furthermore, a detailed study using mAb evidenced that iodination and coupling induced changes in the antigenicity of the molecule, some occurring without direct implication of iodine or thyroid hormones. The 22 kDa peptide appears as an interesting model to study the antigenic changes induced by the structural modifications in the course of thyroid hormone synthesis. This observation could be relevant to the etiopathogenic process of thyroid autoimmune diseases.", "contents": "Tyrosine iodination and iodotyrosyl coupling of the N-terminal thyroid hormone forming site of human thyroglobulin modulate its binding to auto- and monoclonal antibodies. The present work was aimed at studying the interaction of autoantibodies (aAb) and monoclonal antibodies (mAb) with the N-terminal thyroid hormone forming site of human thyroglobulin (TG). Obtained by CNBr treatment of TG, the peptide (22 kDa) containing the complete major hormonogenic site of human TG was purified in three forms according to the degree of iodination and iodotyrosine coupling: the native, poorly iodinated form (n-22K), the iodinated form containing iodotyrosine but not hormone residues (i-22K) and the form containing thyroid hormone (t-22K). We report that aAb from some patients with autoimmune thyroid diseases showed significant binding to both iodinated 22 kDa forms. Furthermore, a detailed study using mAb evidenced that iodination and coupling induced changes in the antigenicity of the molecule, some occurring without direct implication of iodine or thyroid hormones. The 22 kDa peptide appears as an interesting model to study the antigenic changes induced by the structural modifications in the course of thyroid hormone synthesis. This observation could be relevant to the etiopathogenic process of thyroid autoimmune diseases."} {"id": "PMID:1281127", "title": "Direct estradiol down-regulation of secretogranin II and chromogranin A mRNA levels in rat pituitary cells.", "content": "Estradiol (E2) has been previously shown to negatively regulate, in vivo, the secretogranin (SgII) and chromogranin A (CgA) mRNA levels in the rat pituitary. Using cultured pituitary cell aggregates, experiments were undertaken to discriminate between direct or indirect effects of E2 on SgII and CgA levels. SgII, CgA and gonadotropin alpha- and beta-subunit mRNA levels were determined by Northern blotting. SgII and CgA protein levels were quantitated by Western blotting, and by immunoprecipitation of radioactive SgII after [35S]methionine labeling. Increasing concentrations of E2 (from 10(-12) M to 10(-8) M) in the culture medium promoted a decrease of SgII and CgA mRNA levels to 30% and 50% of the control, respectively, after 72.h treatment. By contrast, none of the gonadotropin subunit mRNAs exhibited changes in concentration. A 24 h treatment with 10(-8) M E2 was sufficient to promote such a decrease in SgII and CgA mRNAs. Quantitation of the proteins after Western blotting revealed that 10(-8) M E2 lowered by 30% in CgA content of aggregates (P < 0.05 vs. control) while SgII content remained unaffected. Moreover, quantitation of the newly synthesized SgII by immunoprecipitation of the 35S-labeled SgII gave evidence for a lack of E2 effect. These data demonstrate: (1) a direct effect of E2 on the pituitary cells to down-regulate SgII and CgA mRNA steady-state levels; (2) though contained within the same secretory granules, a distinct pathway for negative E2 regulation of the gonadotropins and both granins; and (3) a differential effect of E2 on cell SgII and CgA contents as was previously demonstrated in vivo.", "contents": "Direct estradiol down-regulation of secretogranin II and chromogranin A mRNA levels in rat pituitary cells. Estradiol (E2) has been previously shown to negatively regulate, in vivo, the secretogranin (SgII) and chromogranin A (CgA) mRNA levels in the rat pituitary. Using cultured pituitary cell aggregates, experiments were undertaken to discriminate between direct or indirect effects of E2 on SgII and CgA levels. SgII, CgA and gonadotropin alpha- and beta-subunit mRNA levels were determined by Northern blotting. SgII and CgA protein levels were quantitated by Western blotting, and by immunoprecipitation of radioactive SgII after [35S]methionine labeling. Increasing concentrations of E2 (from 10(-12) M to 10(-8) M) in the culture medium promoted a decrease of SgII and CgA mRNA levels to 30% and 50% of the control, respectively, after 72.h treatment. By contrast, none of the gonadotropin subunit mRNAs exhibited changes in concentration. A 24 h treatment with 10(-8) M E2 was sufficient to promote such a decrease in SgII and CgA mRNAs. Quantitation of the proteins after Western blotting revealed that 10(-8) M E2 lowered by 30% in CgA content of aggregates (P < 0.05 vs. control) while SgII content remained unaffected. Moreover, quantitation of the newly synthesized SgII by immunoprecipitation of the 35S-labeled SgII gave evidence for a lack of E2 effect. These data demonstrate: (1) a direct effect of E2 on the pituitary cells to down-regulate SgII and CgA mRNA steady-state levels; (2) though contained within the same secretory granules, a distinct pathway for negative E2 regulation of the gonadotropins and both granins; and (3) a differential effect of E2 on cell SgII and CgA contents as was previously demonstrated in vivo."} {"id": "PMID:1281128", "title": "Characterization of muscarinic receptor subtypes on rat pancreatic acini: pharmacological identification by secretory responses and binding studies.", "content": "In order to identify subtypes of muscarinic receptor on the rat pancreas, the effects of new muscarinic receptor antagonists, [11-[[2-(diethylamino)-methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116) and 4-diphenylacetoxy-N-methylpiperadine-methiodide (4-DAMP), on amylase secretion stimulated by carbachol and binding of [3H]quinuclidinyl benzilate (QNB) were evaluated using isolated rat pancreatic acini. Atropine, pirenzepine, AF-DX 116 and 4-DAMP inhibited carbachol-stimulated amylase release in a dose-dependent manner. All these antagonists caused a concentration-dependent rightward shift of the dose-response curve for carbachol-stimulated amylase release without altering the maximal response. Schild plots revealed that pA2 values for atropine, pirenzepine, AF-DX 116 and 4-DAMP were 9.15, 6.78, 6.09 and 8.79, respectively. Every slope of Schild plots was not different from unity, suggesting that these antagonists act as competitive inhibitors. These antagonists also inhibited the binding of [3H]QNB in a dose-dependent manner. The inhibition constants were 1.21 x 10(-9) M (atropine), 1.26 x 10(-7) M (pirenzepine), 0.57 x 10(-6) M (AF-DX 116) and 2.75 x 10(-9) M (4-DAMP). Thus, the order of inhibitory potencies was atropine > or = 4-DAMP > pirenzepine > AF-DX 116. These findings suggest that 4-DAMP-sensitive M3 receptor may play an important role in the pancreatic exocrine functions.", "contents": "Characterization of muscarinic receptor subtypes on rat pancreatic acini: pharmacological identification by secretory responses and binding studies. In order to identify subtypes of muscarinic receptor on the rat pancreas, the effects of new muscarinic receptor antagonists, [11-[[2-(diethylamino)-methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one (AF-DX 116) and 4-diphenylacetoxy-N-methylpiperadine-methiodide (4-DAMP), on amylase secretion stimulated by carbachol and binding of [3H]quinuclidinyl benzilate (QNB) were evaluated using isolated rat pancreatic acini. Atropine, pirenzepine, AF-DX 116 and 4-DAMP inhibited carbachol-stimulated amylase release in a dose-dependent manner. All these antagonists caused a concentration-dependent rightward shift of the dose-response curve for carbachol-stimulated amylase release without altering the maximal response. Schild plots revealed that pA2 values for atropine, pirenzepine, AF-DX 116 and 4-DAMP were 9.15, 6.78, 6.09 and 8.79, respectively. Every slope of Schild plots was not different from unity, suggesting that these antagonists act as competitive inhibitors. These antagonists also inhibited the binding of [3H]QNB in a dose-dependent manner. The inhibition constants were 1.21 x 10(-9) M (atropine), 1.26 x 10(-7) M (pirenzepine), 0.57 x 10(-6) M (AF-DX 116) and 2.75 x 10(-9) M (4-DAMP). Thus, the order of inhibitory potencies was atropine > or = 4-DAMP > pirenzepine > AF-DX 116. These findings suggest that 4-DAMP-sensitive M3 receptor may play an important role in the pancreatic exocrine functions."} {"id": "PMID:1281129", "title": "Reciprocal expression of c-jun, proline-rich protein and amylase genes during rat parotid salivary gland development.", "content": "We have investigated the temporal expression and cellular localization of the c-jun proto-oncogene and two major rat parotid gland secretory protein genes, PRP (proline-rich protein) and amylase, during postnatal development. c-jun mRNA steady-state levels increased at days 1, 7 and 14 after birth and decreased to basal levels at 21 days and older. PRP mRNA was first detected at 14 days and abruptly increased to adult levels at day 21. Amylase transcripts were first seen at day 7 and progressively increased to adult levels by 28 days. In situ hybridization demonstrated c-jun mRNA accumulation in the differentiating acinar cells and the ducts. The c-jun mRNA accumulation with time corresponds with the proliferative activity reported to occur in these two cellular populations. PRP transcripts were present exclusively in the well differentiated acinar cells while the accumulation of amylase mRNA corresponded to the progressive commitment of parotid cells to acinar differentiation. Our data suggest that during the postnatal development of the rat parotid gland: (a) c-jun expression associates with parotid gland proliferation and precedes the expression of PRP and amylase genes, and (b) activation of PRP and amylase genes is not concomitant and apparently occurs only in differentiating acinar cells.", "contents": "Reciprocal expression of c-jun, proline-rich protein and amylase genes during rat parotid salivary gland development. We have investigated the temporal expression and cellular localization of the c-jun proto-oncogene and two major rat parotid gland secretory protein genes, PRP (proline-rich protein) and amylase, during postnatal development. c-jun mRNA steady-state levels increased at days 1, 7 and 14 after birth and decreased to basal levels at 21 days and older. PRP mRNA was first detected at 14 days and abruptly increased to adult levels at day 21. Amylase transcripts were first seen at day 7 and progressively increased to adult levels by 28 days. In situ hybridization demonstrated c-jun mRNA accumulation in the differentiating acinar cells and the ducts. The c-jun mRNA accumulation with time corresponds with the proliferative activity reported to occur in these two cellular populations. PRP transcripts were present exclusively in the well differentiated acinar cells while the accumulation of amylase mRNA corresponded to the progressive commitment of parotid cells to acinar differentiation. Our data suggest that during the postnatal development of the rat parotid gland: (a) c-jun expression associates with parotid gland proliferation and precedes the expression of PRP and amylase genes, and (b) activation of PRP and amylase genes is not concomitant and apparently occurs only in differentiating acinar cells."} {"id": "PMID:1281130", "title": "Nucleotide sequence of the nfaA gene encoding the antigen 8786 adhesive factor of enterotoxigenic Escherichia coli.", "content": "The nucleotide sequence of a 714-bp DNA fragment containing the enterotoxic Escherichia coli (ETEC) adhesive factor 8786 structural gene, designated nfaA, revealed an open reading frame of 498 bp encoding a polypeptide of 166 amino acids. Primer-extension experiments showed that the nfaA gene is within a single transcription unit. No homology was found with the ETEC adhesive factors already sequenced. In contrast, a homology with Salmonella enteritidis fimbrin SEF 14 was observed.", "contents": "Nucleotide sequence of the nfaA gene encoding the antigen 8786 adhesive factor of enterotoxigenic Escherichia coli. The nucleotide sequence of a 714-bp DNA fragment containing the enterotoxic Escherichia coli (ETEC) adhesive factor 8786 structural gene, designated nfaA, revealed an open reading frame of 498 bp encoding a polypeptide of 166 amino acids. Primer-extension experiments showed that the nfaA gene is within a single transcription unit. No homology was found with the ETEC adhesive factors already sequenced. In contrast, a homology with Salmonella enteritidis fimbrin SEF 14 was observed."} {"id": "PMID:1281131", "title": "Transcription in vitro and in vivo of the 7S RNA gene associated with the ribosomal RNA operon in the hyperthermophilic archaeon Methanothermus fervidus.", "content": "The gene encoding the archaeal 7S RNA in the hyperthermophile Methanothermus fervidus is linked to a tRNA(Ser) and rRNA operon in the arrangement 5'-7S RNA-14nt-tRNA(Ser)-196nt-16S rRNA and the promoter directing transcription of this 7S RNA gene has now been identified. Initiation of transcription of the 7S RNA gene has been shown to occur both in vivo in M. fervidus and in vitro, using a Methanococcus thermolithotrophicus derived cell-free transcription system, at the first G residue within the initiator sequence ATGG, located 6 bp upstream of the 5' end of the 7S RNA coding region. Cotranscription of the 7S RNA and tRNA(Ser) has been demonstrated in vitro.", "contents": "Transcription in vitro and in vivo of the 7S RNA gene associated with the ribosomal RNA operon in the hyperthermophilic archaeon Methanothermus fervidus. The gene encoding the archaeal 7S RNA in the hyperthermophile Methanothermus fervidus is linked to a tRNA(Ser) and rRNA operon in the arrangement 5'-7S RNA-14nt-tRNA(Ser)-196nt-16S rRNA and the promoter directing transcription of this 7S RNA gene has now been identified. Initiation of transcription of the 7S RNA gene has been shown to occur both in vivo in M. fervidus and in vitro, using a Methanococcus thermolithotrophicus derived cell-free transcription system, at the first G residue within the initiator sequence ATGG, located 6 bp upstream of the 5' end of the 7S RNA coding region. Cotranscription of the 7S RNA and tRNA(Ser) has been demonstrated in vitro."} {"id": "PMID:1281132", "title": "The effect of superoxide dismutase in the myocardium during reperfusion in the dog.", "content": "The aim of the study was to investigate the pathological role of free radicals during myocardial reperfusion. Low (0.5 mg/kg body weight) and high doses (5 mg/kg) of superoxide dismutase (SOD) were infused into the left atrium of mongrel dogs for 4 min starting 29 min after ligation and 1 min before reperfusion of the left anterior descending coronary artery (LAD). Arterial blood pressure, heart rate, electrocardiogram, and the regional contractile force of the left ventricle were monitored throughout the ligation (30 min) and reperfusion periods (20 min). Concentrations of creatine kinase (CK) and malondialdehyde (MDA) in the coronary sinus blood were determined before (0 min) and during ligation (15 and 25 min) and during reperfusion of the LAD (2, 7, and 20 min). In other groups of dogs, the effect of the two doses of SOD on epicardial blood flow was investigated during ligation and reperfusion by the measurement of epicardial temperature using a thermocardiograph. Experimental subjects were mongrel dogs of either sex (n = 25), weight 10-35 kg. Compared to controls (mean +/- SEM, 43.1 +/- 1.2; n = 7), the number of ventricular extrasystoles during the first 5 min of reperfusion was significantly (p < .001) decreased in dogs treated with the high dose (15.01 +/- 2.14; n = 5), but not in those receiving the low dose of the drug (34.6 +/- 5.66; n = 5). The concentrations of CK increased gradually until the end of reperfusion without differences among the different groups. Plasma MDA was the highest in control dogs 7 min after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "The effect of superoxide dismutase in the myocardium during reperfusion in the dog. The aim of the study was to investigate the pathological role of free radicals during myocardial reperfusion. Low (0.5 mg/kg body weight) and high doses (5 mg/kg) of superoxide dismutase (SOD) were infused into the left atrium of mongrel dogs for 4 min starting 29 min after ligation and 1 min before reperfusion of the left anterior descending coronary artery (LAD). Arterial blood pressure, heart rate, electrocardiogram, and the regional contractile force of the left ventricle were monitored throughout the ligation (30 min) and reperfusion periods (20 min). Concentrations of creatine kinase (CK) and malondialdehyde (MDA) in the coronary sinus blood were determined before (0 min) and during ligation (15 and 25 min) and during reperfusion of the LAD (2, 7, and 20 min). In other groups of dogs, the effect of the two doses of SOD on epicardial blood flow was investigated during ligation and reperfusion by the measurement of epicardial temperature using a thermocardiograph. Experimental subjects were mongrel dogs of either sex (n = 25), weight 10-35 kg. Compared to controls (mean +/- SEM, 43.1 +/- 1.2; n = 7), the number of ventricular extrasystoles during the first 5 min of reperfusion was significantly (p < .001) decreased in dogs treated with the high dose (15.01 +/- 2.14; n = 5), but not in those receiving the low dose of the drug (34.6 +/- 5.66; n = 5). The concentrations of CK increased gradually until the end of reperfusion without differences among the different groups. Plasma MDA was the highest in control dogs 7 min after reperfusion.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281133", "title": "MspI polymorphism of the apolipoprotein A-II gene, serum lipids and apolipoproteins in Chinese from Singapore.", "content": "The effect of a DNA polymorphism (MspI) of the apolipoprotein (apo) A-II gene on serum lipid and apo levels was studied in a group of 125 healthy Chinese of both sexes. The frequency of the 3.7-kb rarer allele (M2) was found to be significantly higher in the Chinese (0.30) than in Caucasians (0.16; p < 0.025). The distribution of apo A-II genotypes was in Hardy-Weinberg equilibrium in the Chinese population. The presence of a polymorphic site (MspI) within an Alu sequence at the 3' end of the gene, the 3.0 kb (M1) allele, was associated with significantly higher levels of serum apo A-I and A-II (p < 0.05 and < 0.01, respectively). Serum high-density Lipoprotein cholesterol levels were also correspondingly higher in individuals with M1, but did not reach a significant level. Male heterozygotes of the apo A-II polymorphism had significantly higher levels of serum triglycerides compared to homozygotes (p < 0.05). Thus the MspI polymorphism of the apo A-II gene appears to be associated with altered levels of lipids and apos in the Chinese population.", "contents": "MspI polymorphism of the apolipoprotein A-II gene, serum lipids and apolipoproteins in Chinese from Singapore. The effect of a DNA polymorphism (MspI) of the apolipoprotein (apo) A-II gene on serum lipid and apo levels was studied in a group of 125 healthy Chinese of both sexes. The frequency of the 3.7-kb rarer allele (M2) was found to be significantly higher in the Chinese (0.30) than in Caucasians (0.16; p < 0.025). The distribution of apo A-II genotypes was in Hardy-Weinberg equilibrium in the Chinese population. The presence of a polymorphic site (MspI) within an Alu sequence at the 3' end of the gene, the 3.0 kb (M1) allele, was associated with significantly higher levels of serum apo A-I and A-II (p < 0.05 and < 0.01, respectively). Serum high-density Lipoprotein cholesterol levels were also correspondingly higher in individuals with M1, but did not reach a significant level. Male heterozygotes of the apo A-II polymorphism had significantly higher levels of serum triglycerides compared to homozygotes (p < 0.05). Thus the MspI polymorphism of the apo A-II gene appears to be associated with altered levels of lipids and apos in the Chinese population."} {"id": "PMID:1281134", "title": "Use of monoclonal antibodies for discrimination between natural and recombinant human interferon-tau.", "content": "Different monoclonal antibodies (MAbs) were raised against denaturated and native recombinant human Interferon-tau (IFN-tau). This approach gave us MAbs which recognized either N-term (prepared with SDS-denaturated IFN-tau) or C-terminal part of the antigen as well as MAbs which linked to non linear epitopes (obtained with native form of IFN-tau). Some of them inhibited or enhanced their respective binding to IFN-tau. After characterization, these antibodies were used as probes and some were selected to prepare two quantitative sensitive sandwich IRMAs able to discriminate between recombinant and natural IFN-tau.", "contents": "Use of monoclonal antibodies for discrimination between natural and recombinant human interferon-tau. Different monoclonal antibodies (MAbs) were raised against denaturated and native recombinant human Interferon-tau (IFN-tau). This approach gave us MAbs which recognized either N-term (prepared with SDS-denaturated IFN-tau) or C-terminal part of the antigen as well as MAbs which linked to non linear epitopes (obtained with native form of IFN-tau). Some of them inhibited or enhanced their respective binding to IFN-tau. After characterization, these antibodies were used as probes and some were selected to prepare two quantitative sensitive sandwich IRMAs able to discriminate between recombinant and natural IFN-tau."} {"id": "PMID:1281135", "title": "Development of human monoclonal antibodies against human cytomegalovirus.", "content": "Human monoclonal antibodies (HMAbs) against human cytomegalovirus (HCMV) have been developed by fusion of human spleen cells and human lymphoblastoid cell lines (NP101 and NP197). The cell line NP101 had great advantages in its high fusion frequency and the stability of the resultant hybridomas. The specificity of HMAbs was confirmed by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. Two of the six HMAbs obtained, which were IgG3 subclass, neutralized viral infectivity in the absence of complement. The neutralizing activity of one of these two HMAbs was enhanced in the presence of human complement, whereas the other was not. Another IgG1 subclass HMAb neutralized viral infection only in the presence of complement. The remaining three HMAbs showed no neutralizing activity. Those HMAbs may provide an important approach to studying human immune responses to HCMV. HMAbs having neutralizing activity may prove to be useful for passive immunotherapy of HCMV diseases.", "contents": "Development of human monoclonal antibodies against human cytomegalovirus. Human monoclonal antibodies (HMAbs) against human cytomegalovirus (HCMV) have been developed by fusion of human spleen cells and human lymphoblastoid cell lines (NP101 and NP197). The cell line NP101 had great advantages in its high fusion frequency and the stability of the resultant hybridomas. The specificity of HMAbs was confirmed by enzyme-linked immunosorbent assay (ELISA) and immunofluorescence staining. Two of the six HMAbs obtained, which were IgG3 subclass, neutralized viral infectivity in the absence of complement. The neutralizing activity of one of these two HMAbs was enhanced in the presence of human complement, whereas the other was not. Another IgG1 subclass HMAb neutralized viral infection only in the presence of complement. The remaining three HMAbs showed no neutralizing activity. Those HMAbs may provide an important approach to studying human immune responses to HCMV. HMAbs having neutralizing activity may prove to be useful for passive immunotherapy of HCMV diseases."} {"id": "PMID:1281136", "title": "Monoclonal antibodies against heavy and light chains of domestic mink IgG.", "content": "A panel of 26 monoclonal antibodies (MAbs) specific to mink IgG was produced and analyzed by ELISA, immunodiffusion assay (IDA) and immunoblotting assay. All the raised MAbs were directed against the isotypic IgG epitopes. Immunoblotting assay demonstrated that 11 MAbs reacted only with the Fc-fragments of IgG and 7 only with the light chains. Four antibodies bound to the Fab-containing fragments and failed to react with the Fc-fragments or isolated L-chains. Three MAbs did not react with IgG in IDA. Based on the results of IDA and cross-blocking assays, the MAbs were divided into 10 groups, with the MAbs of each group recognizing the same epitope. In IDA some MAbs were able to react with the epitopes which are common to the IgGs of some other representatives of Mustelidae family and also to some mammalian species remote from mink (dog, horse, pig, fox and rabbit).", "contents": "Monoclonal antibodies against heavy and light chains of domestic mink IgG. A panel of 26 monoclonal antibodies (MAbs) specific to mink IgG was produced and analyzed by ELISA, immunodiffusion assay (IDA) and immunoblotting assay. All the raised MAbs were directed against the isotypic IgG epitopes. Immunoblotting assay demonstrated that 11 MAbs reacted only with the Fc-fragments of IgG and 7 only with the light chains. Four antibodies bound to the Fab-containing fragments and failed to react with the Fc-fragments or isolated L-chains. Three MAbs did not react with IgG in IDA. Based on the results of IDA and cross-blocking assays, the MAbs were divided into 10 groups, with the MAbs of each group recognizing the same epitope. In IDA some MAbs were able to react with the epitopes which are common to the IgGs of some other representatives of Mustelidae family and also to some mammalian species remote from mink (dog, horse, pig, fox and rabbit)."} {"id": "PMID:1281137", "title": "Influence of exposure to tobacco smoke on serum alpha fetoprotein levels of women in midtrimester pregnancy.", "content": "The influence of exposure to tobacco smoke on maternal serum alpha-fetoprotein (AFP) levels at 16 wk gestation was examined. Urinary cotinine levels were used to quantify exposure to tobacco smoke. Significantly higher levels of maternal serum AFP were found in 101 women who had more than 1.0 microgram cotinine/mg urinary creatinine compared with 180 women whose urinary cotinine levels were below this level [(mean +/- SD) 1.23 +/- 0.64 and 1.06 +/- 0.54 respectively; 95 per cent CI of difference of means 0.01-0.31; P < 0.05]. There was a mild albeit statistically significant correlation between urinary cotinine levels and maternal serum AFB (r 0.099; P < 0.05). However, the difference in maternal serum AFP levels between the two groups was not found to be significant, when adjustments for maternal body mass index were made.", "contents": "Influence of exposure to tobacco smoke on serum alpha fetoprotein levels of women in midtrimester pregnancy. The influence of exposure to tobacco smoke on maternal serum alpha-fetoprotein (AFP) levels at 16 wk gestation was examined. Urinary cotinine levels were used to quantify exposure to tobacco smoke. Significantly higher levels of maternal serum AFP were found in 101 women who had more than 1.0 microgram cotinine/mg urinary creatinine compared with 180 women whose urinary cotinine levels were below this level [(mean +/- SD) 1.23 +/- 0.64 and 1.06 +/- 0.54 respectively; 95 per cent CI of difference of means 0.01-0.31; P < 0.05]. There was a mild albeit statistically significant correlation between urinary cotinine levels and maternal serum AFB (r 0.099; P < 0.05). However, the difference in maternal serum AFP levels between the two groups was not found to be significant, when adjustments for maternal body mass index were made."} {"id": "PMID:1281142", "title": "des-(1-3)-IGF-I, an insulin-like growth factor analog used to mimic a potential IGF-II autocrine loop, promotes the differentiation of human colon-carcinoma cells.", "content": "HT29-D4 human colon-carcinoma cells have been shown to secrete insulin-like growth factor (IGF)-II and to simultaneously express type-I IGF receptors. However, the sequestration of IGF-II by several molecular forms of IGF-binding proteins (IGFBP) in the culture medium prevents the establishment of an operative IGF-II autocrine loop. IGFBPs secreted by HT29-D4 cells (HT29-D4 IGFBP) comprise isoforms of IGFBP-4 (25, 27 and 30 kDa) and 2 unidentified forms (34.5 and 32-34 kDa). This latter does not bind 125I-IGF-I. The net affinity of HT29-D4 IGFBP is about 12 times stronger for IGF-II (KD approx. 10(-10) M) than for IGF-I. All the HT29-D4 IGFBP molecular forms are unable to bind the N-terminally truncated IGF-I analog, des-(1-3)-IGF-I. In contrast, HT29-D4 cell-surface type-I IGF receptors bind IGF-I and des-(1-3)-IGF-I identically (KD approx. 5 x 10(-10) M). We have taken advantage of these particular binding properties to use des-(1-3)-IGF-I to mimic a potential IGF autocrine loop and to observe its biological consequences. Nanomolar concentrations of des-(1-3)-IGF-I induce HT29-D4 cells to develop into a differentiated phenotype, as judged by a substantial carcinoembryonic antigen release and the induction of numerous intercellular cysts with well-organized microvilli. In the same way, des-(1-3)-IGF-I early induces a slight inhibition of HT29-D4 cell proliferation. Based on these findings, we conclude that the type-I IGF receptor primarily controls the differentiation of these colonic cells, and that HT29-D4 cancer cells remain in an undifferentiated state because of their inability to use endogenous IGF-II as an autocrine regulatory factor.", "contents": "des-(1-3)-IGF-I, an insulin-like growth factor analog used to mimic a potential IGF-II autocrine loop, promotes the differentiation of human colon-carcinoma cells. HT29-D4 human colon-carcinoma cells have been shown to secrete insulin-like growth factor (IGF)-II and to simultaneously express type-I IGF receptors. However, the sequestration of IGF-II by several molecular forms of IGF-binding proteins (IGFBP) in the culture medium prevents the establishment of an operative IGF-II autocrine loop. IGFBPs secreted by HT29-D4 cells (HT29-D4 IGFBP) comprise isoforms of IGFBP-4 (25, 27 and 30 kDa) and 2 unidentified forms (34.5 and 32-34 kDa). This latter does not bind 125I-IGF-I. The net affinity of HT29-D4 IGFBP is about 12 times stronger for IGF-II (KD approx. 10(-10) M) than for IGF-I. All the HT29-D4 IGFBP molecular forms are unable to bind the N-terminally truncated IGF-I analog, des-(1-3)-IGF-I. In contrast, HT29-D4 cell-surface type-I IGF receptors bind IGF-I and des-(1-3)-IGF-I identically (KD approx. 5 x 10(-10) M). We have taken advantage of these particular binding properties to use des-(1-3)-IGF-I to mimic a potential IGF autocrine loop and to observe its biological consequences. Nanomolar concentrations of des-(1-3)-IGF-I induce HT29-D4 cells to develop into a differentiated phenotype, as judged by a substantial carcinoembryonic antigen release and the induction of numerous intercellular cysts with well-organized microvilli. In the same way, des-(1-3)-IGF-I early induces a slight inhibition of HT29-D4 cell proliferation. Based on these findings, we conclude that the type-I IGF receptor primarily controls the differentiation of these colonic cells, and that HT29-D4 cancer cells remain in an undifferentiated state because of their inability to use endogenous IGF-II as an autocrine regulatory factor."} {"id": "PMID:1281143", "title": "VLA-4 integrin on sarcoma cell lines recognizes endothelial VCAM-1. Differential regulation of the VLA-4 avidity on various sarcoma cell lines.", "content": "Osteosarcomas and rhabdomyosarcomas are vigorously invading tumors. Before they can extravasate to the parenchymal organs and form metastases, they have to adhere to the endothelial cells lining the blood vessels and then penetrate through the endothelium. We show that several human sarcoma cell lines, osteosarcomas HOS, MG-63, U2-OS, and a rhabdomyosarcoma RD, express VLA-4 molecule on their surface and bind to the VCAM-I-expressing activated endothelial cell line Ea.hy 926. The increased sarcoma-cell adhesion could be abolished by treating the sarcoma cells with monoclonal antibodies (MAbs) VLA4 (both alpha- and beta-chain, HP2/1 and 4B4 respectively) or treating endothelial cells with VCAM-I antibody (4B9). Furthermore, we show that sarcoma cells adhere to recombinant soluble VCAM-I protein. On the other hand, these sarcoma cell lines do not express marked amounts of other ligands (such as CDII/18 or sialyl-Lex) for other endothelial adhesion molecules (ICAM-I, ICAM-2, E- and P-selectin) indicating that the VLA-4-VCAM-I dependent pathway might be of major importance in sarcoma extravasation. VLA-4 is not always in an avid form and therefore the expression of VLA-4 does not directly predict adherence to VCAM-I. The avidity of VLA-4 (measured by adherence to soluble VCAM-I) of MG-63 and U2-OS cells could be increased by a 30-min PMA treatment, whereas the avidity of VLA-4 on HOS cells increased only after 48 hr of PMA induction. Our results show that sarcoma cell lines (HOS, MG-63, U2-OS and RD) adhere to stimulated endothelium via VLA-4-VCAM-I adhesion molecules and that VLA-4 avidity on sarcoma cells can be differentially modulated by PMA.", "contents": "VLA-4 integrin on sarcoma cell lines recognizes endothelial VCAM-1. Differential regulation of the VLA-4 avidity on various sarcoma cell lines. Osteosarcomas and rhabdomyosarcomas are vigorously invading tumors. Before they can extravasate to the parenchymal organs and form metastases, they have to adhere to the endothelial cells lining the blood vessels and then penetrate through the endothelium. We show that several human sarcoma cell lines, osteosarcomas HOS, MG-63, U2-OS, and a rhabdomyosarcoma RD, express VLA-4 molecule on their surface and bind to the VCAM-I-expressing activated endothelial cell line Ea.hy 926. The increased sarcoma-cell adhesion could be abolished by treating the sarcoma cells with monoclonal antibodies (MAbs) VLA4 (both alpha- and beta-chain, HP2/1 and 4B4 respectively) or treating endothelial cells with VCAM-I antibody (4B9). Furthermore, we show that sarcoma cells adhere to recombinant soluble VCAM-I protein. On the other hand, these sarcoma cell lines do not express marked amounts of other ligands (such as CDII/18 or sialyl-Lex) for other endothelial adhesion molecules (ICAM-I, ICAM-2, E- and P-selectin) indicating that the VLA-4-VCAM-I dependent pathway might be of major importance in sarcoma extravasation. VLA-4 is not always in an avid form and therefore the expression of VLA-4 does not directly predict adherence to VCAM-I. The avidity of VLA-4 (measured by adherence to soluble VCAM-I) of MG-63 and U2-OS cells could be increased by a 30-min PMA treatment, whereas the avidity of VLA-4 on HOS cells increased only after 48 hr of PMA induction. Our results show that sarcoma cell lines (HOS, MG-63, U2-OS and RD) adhere to stimulated endothelium via VLA-4-VCAM-I adhesion molecules and that VLA-4 avidity on sarcoma cells can be differentially modulated by PMA."} {"id": "PMID:1281144", "title": "The usefulness of ethylephrine (Efortil-R) in the treatment of priapism and intraoperative penile erections.", "content": "We present our experience in the treatment of 8 patients with priapism after intravenous injection of vasoactive drugs, and of 15 patients with persistent erections in the course of transurethral cystoscopy surgery. All of them were treated with intracavernous injection of 10 mg ethylephrine (1 ml Efortil-R). The results were satisfactory in all cases. In one patient we had to draw 75 ml blood and give another 10 mg dose of ethylephrine. We have not observed secondary effects of drug administration except two local haematomas with spontaneous resolution. We consider that this treatment is very useful in the management of patients with persistent erections or priapism because of the excellent results obtained without adverse effects.", "contents": "The usefulness of ethylephrine (Efortil-R) in the treatment of priapism and intraoperative penile erections. We present our experience in the treatment of 8 patients with priapism after intravenous injection of vasoactive drugs, and of 15 patients with persistent erections in the course of transurethral cystoscopy surgery. All of them were treated with intracavernous injection of 10 mg ethylephrine (1 ml Efortil-R). The results were satisfactory in all cases. In one patient we had to draw 75 ml blood and give another 10 mg dose of ethylephrine. We have not observed secondary effects of drug administration except two local haematomas with spontaneous resolution. We consider that this treatment is very useful in the management of patients with persistent erections or priapism because of the excellent results obtained without adverse effects."} {"id": "PMID:1281145", "title": "The prognostic value of prostate-specific antigen and prostatic acid phosphatase in serum of patients with prostate cancer after orchidectomy.", "content": "Correlations between the serum levels of PAP and PSA before and 1, 3 and 6 months after orchidectomy in 27 prostatic cancer patients (advanced clinical stages C and D according to Whitemore scale) were studied. The PSA values correlated more distinctly than PAP with the general clinical condition. PSA is a reliable tumour marker when used at regular intervals, especially for monitoring therapeutic results. A high preoperative PSA level correlates with a high postoperative level and progression of the disease.", "contents": "The prognostic value of prostate-specific antigen and prostatic acid phosphatase in serum of patients with prostate cancer after orchidectomy. Correlations between the serum levels of PAP and PSA before and 1, 3 and 6 months after orchidectomy in 27 prostatic cancer patients (advanced clinical stages C and D according to Whitemore scale) were studied. The PSA values correlated more distinctly than PAP with the general clinical condition. PSA is a reliable tumour marker when used at regular intervals, especially for monitoring therapeutic results. A high preoperative PSA level correlates with a high postoperative level and progression of the disease."} {"id": "PMID:1281146", "title": "Immunological detection of nitric oxide synthase(s) in human tissues using heterologous antibodies suggesting different isoforms.", "content": "Nitric oxide (NO) is generated from L-arginine by NO synthases. Localization of the brain enzyme has been carried out in the rat; however, despite data suggesting that NO is a major regulator of vascular and neural functions in man, there is no information about the localization of NO synthase in human tissues. Rabbit antisera to NO synthase purified from rat brain (antisera A and B) were raised, tested by Western blotting, affinity purification and enzyme immunoprecipitation assay, and used to investigate the distribution of the enzyme in a variety of human tissues by immunohistochemistry. Antisera to two synthetic peptides from cloned neural NO synthase were used to aid specificity testing. Anti-sera A and B reacted with a approximately 160-kDa protein in Western blots of human brain extracts, gave immunostaining of nerves, and precipitated enzyme activity from rat brain homogenates. Antiserum B to NO synthase also reacted with proteins of M(r) between 125 and 140 kDa in extracts of well-vascularised tissues, and immunostained vascular endothelium; the neural and vascular immunoreactivity persisted after affinity purification of antiserum B with the approximately 160 kDa protein. Endothelial staining with antiserum B was seen in respiratory tract, liver, skin and umbilicus; syncytial trophoblasts stained in the placenta. Neural staining with antiserum A and B was seen in the myenteric and submucous plexus, and in nerve fibres in smooth muscle of the gut and in many areas of the central nervous system, particularly cortex, hippocampus, hypothalamus, cerebellum, brain stem and spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Immunological detection of nitric oxide synthase(s) in human tissues using heterologous antibodies suggesting different isoforms. Nitric oxide (NO) is generated from L-arginine by NO synthases. Localization of the brain enzyme has been carried out in the rat; however, despite data suggesting that NO is a major regulator of vascular and neural functions in man, there is no information about the localization of NO synthase in human tissues. Rabbit antisera to NO synthase purified from rat brain (antisera A and B) were raised, tested by Western blotting, affinity purification and enzyme immunoprecipitation assay, and used to investigate the distribution of the enzyme in a variety of human tissues by immunohistochemistry. Antisera to two synthetic peptides from cloned neural NO synthase were used to aid specificity testing. Anti-sera A and B reacted with a approximately 160-kDa protein in Western blots of human brain extracts, gave immunostaining of nerves, and precipitated enzyme activity from rat brain homogenates. Antiserum B to NO synthase also reacted with proteins of M(r) between 125 and 140 kDa in extracts of well-vascularised tissues, and immunostained vascular endothelium; the neural and vascular immunoreactivity persisted after affinity purification of antiserum B with the approximately 160 kDa protein. Endothelial staining with antiserum B was seen in respiratory tract, liver, skin and umbilicus; syncytial trophoblasts stained in the placenta. Neural staining with antiserum A and B was seen in the myenteric and submucous plexus, and in nerve fibres in smooth muscle of the gut and in many areas of the central nervous system, particularly cortex, hippocampus, hypothalamus, cerebellum, brain stem and spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281147", "title": "Single-base mutations at position 2661 of Escherichia coli 23S rRNA increase efficiency of translational proofreading.", "content": "Two single-base substitutions were constructed in the 2660 loop of Escherichia coli 23S rRNA (G2661-->C or U) and were introduced into the rrnB operon cloned in plasmid pKK3535. Ribosomes were isolated from bacteria transformed with the mutated plasmids and assayed in vitro in a poly(U)-directed system for their response to the misreading effect of streptomycin, neomycin, and gentamicin, three aminoglycoside antibiotics known to impair the proofreading control of translational accuracy. Both mutations decreased the stimulation of misreading by these drugs, but neither interfered with their binding to the ribosome. The response of the mutant ribosomes to these drugs suggests that the 2660 loop, which belongs to the elongation factor Tu binding site, is involved in the proofreading step of the accuracy control. In vivo, both mutations reduced read-through of nonsense codons and frameshifting, which can also be related to the increased efficiency in proofreading control which they confer to ribosomes.", "contents": "Single-base mutations at position 2661 of Escherichia coli 23S rRNA increase efficiency of translational proofreading. Two single-base substitutions were constructed in the 2660 loop of Escherichia coli 23S rRNA (G2661-->C or U) and were introduced into the rrnB operon cloned in plasmid pKK3535. Ribosomes were isolated from bacteria transformed with the mutated plasmids and assayed in vitro in a poly(U)-directed system for their response to the misreading effect of streptomycin, neomycin, and gentamicin, three aminoglycoside antibiotics known to impair the proofreading control of translational accuracy. Both mutations decreased the stimulation of misreading by these drugs, but neither interfered with their binding to the ribosome. The response of the mutant ribosomes to these drugs suggests that the 2660 loop, which belongs to the elongation factor Tu binding site, is involved in the proofreading step of the accuracy control. In vivo, both mutations reduced read-through of nonsense codons and frameshifting, which can also be related to the increased efficiency in proofreading control which they confer to ribosomes."} {"id": "PMID:1281148", "title": "Structures of the O1B and O1C lipopolysaccharide antigens of Escherichia coli.", "content": "The O-specific moieties of the O1B antigen (lipopolysaccharide) from Escherichia coli O1B:K1 and the O1C antigen from E. coli O1C:K- both consist of L-rhamnose, D-galactose, N-acetyl-D-glucosamine, and N-acetyl-D-mannosamine in a molar ratio of 2:1:1:1. By using fragmentation procedures, methylation analysis, and one- and two-dimensional nuclear magnetic resonance spectroscopy, the structures of these polysaccharides were found to be [formula: see text] In the O1B polysaccharide X is 2, and in the O1C polysaccharide X is 3. With the recently published structure of the O1A polysaccharides (B. Jann, A. S. Shashkov, D. S. Gupta, S. M. Panasenko, and K. Jann, Carbohydr. Polym. 18:51-57 1992), three related O1 antigens are now known. Their common (O1-specific) epitope is suggested to be the side-chain N-acetyl-D-mannosamine residue.", "contents": "Structures of the O1B and O1C lipopolysaccharide antigens of Escherichia coli. The O-specific moieties of the O1B antigen (lipopolysaccharide) from Escherichia coli O1B:K1 and the O1C antigen from E. coli O1C:K- both consist of L-rhamnose, D-galactose, N-acetyl-D-glucosamine, and N-acetyl-D-mannosamine in a molar ratio of 2:1:1:1. By using fragmentation procedures, methylation analysis, and one- and two-dimensional nuclear magnetic resonance spectroscopy, the structures of these polysaccharides were found to be [formula: see text] In the O1B polysaccharide X is 2, and in the O1C polysaccharide X is 3. With the recently published structure of the O1A polysaccharides (B. Jann, A. S. Shashkov, D. S. Gupta, S. M. Panasenko, and K. Jann, Carbohydr. Polym. 18:51-57 1992), three related O1 antigens are now known. Their common (O1-specific) epitope is suggested to be the side-chain N-acetyl-D-mannosamine residue."} {"id": "PMID:1281149", "title": "Acholeplasma laidlawii has tRNA genes in the 16S-23S spacer of the rRNA operon.", "content": "We amplified the 16S-23S rRNA intergenic spacer region of Acholeplasma laidlawii PG8 by polymerase chain reaction (PCR) and obtained two specific PCR products in different sizes. We have sequenced both PCR products and found that one of them has sequence homologous to the spacer tRNA genes in Bacillus subtilis. This is the first evidence of tRNA genes between the 16S-23S rRNA intergenic spacer regions in members of the class Mollicutes.", "contents": "Acholeplasma laidlawii has tRNA genes in the 16S-23S spacer of the rRNA operon. We amplified the 16S-23S rRNA intergenic spacer region of Acholeplasma laidlawii PG8 by polymerase chain reaction (PCR) and obtained two specific PCR products in different sizes. We have sequenced both PCR products and found that one of them has sequence homologous to the spacer tRNA genes in Bacillus subtilis. This is the first evidence of tRNA genes between the 16S-23S rRNA intergenic spacer regions in members of the class Mollicutes."} {"id": "PMID:1281150", "title": "Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation.", "content": "Using conditions that produced chronic inflammation in rat liver, we were able to find a correlation between induction of nitric oxide production and inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12). This enzyme is a tetramer composed of identical M(r) 37,000 subunits. The tetramer contains 16 thiol groups, four of which are essential for enzymatic activity. Our information indicates that four thiol groups are S-nitrosylated by exposure to authentic nitric oxide (NO) gas. Furthermore, NO decreased GAPDH activity while increasing its auto-ADP-ribosylation. Reduced nicotinamide adenine dinucleotide and dithiothreitol are required for the S-nitrosylation of GAPDH caused by the NO-generating compound sodium nitroprusside. Our results suggests that a new and important action of nitric oxide on cells is the S-nitrosylation and inactivation of GAPDH. S-Nitrosylation of GAPDH may be a key covalent modification of multiple regulatory consequences in chronic liver inflammation.", "contents": "Nitric oxide-induced S-nitrosylation of glyceraldehyde-3-phosphate dehydrogenase inhibits enzymatic activity and increases endogenous ADP-ribosylation. Using conditions that produced chronic inflammation in rat liver, we were able to find a correlation between induction of nitric oxide production and inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH; EC 1.2.1.12). This enzyme is a tetramer composed of identical M(r) 37,000 subunits. The tetramer contains 16 thiol groups, four of which are essential for enzymatic activity. Our information indicates that four thiol groups are S-nitrosylated by exposure to authentic nitric oxide (NO) gas. Furthermore, NO decreased GAPDH activity while increasing its auto-ADP-ribosylation. Reduced nicotinamide adenine dinucleotide and dithiothreitol are required for the S-nitrosylation of GAPDH caused by the NO-generating compound sodium nitroprusside. Our results suggests that a new and important action of nitric oxide on cells is the S-nitrosylation and inactivation of GAPDH. S-Nitrosylation of GAPDH may be a key covalent modification of multiple regulatory consequences in chronic liver inflammation."} {"id": "PMID:1281151", "title": "Phorbol esters induce nitric oxide synthase activity in rat hepatocytes. Antagonism with the induction elicited by lipopolysaccharide.", "content": "The incubation of primary cultures of rat hepatocytes with lipopolysaccharide (LPS) or biologically active phorbol esters promotes the release of nitric oxide to the incubation medium. This process is the result of the induction of the Ca(2+)-and calmodulin-independent form of nitric oxide synthase. Both the release of nitric oxide to the incubation medium and the expression of nitric oxide synthase activity exhibited a lag period of about 45-60 min after cell stimulation. Exposure of hepatocytes to both stimuli produced an antagonistic effect on nitric oxide release, with a half-maximal inhibition obtained with 14 nM phorbol 12,13-dibutyrate at saturating concentration of LPS. Incubation of cells with alpha-phorbol 12,13-didecanoate failed to counteract the effect of LPS or to induce nitric oxide synthase, suggesting that activation of protein kinase C was involved in this process.", "contents": "Phorbol esters induce nitric oxide synthase activity in rat hepatocytes. Antagonism with the induction elicited by lipopolysaccharide. The incubation of primary cultures of rat hepatocytes with lipopolysaccharide (LPS) or biologically active phorbol esters promotes the release of nitric oxide to the incubation medium. This process is the result of the induction of the Ca(2+)-and calmodulin-independent form of nitric oxide synthase. Both the release of nitric oxide to the incubation medium and the expression of nitric oxide synthase activity exhibited a lag period of about 45-60 min after cell stimulation. Exposure of hepatocytes to both stimuli produced an antagonistic effect on nitric oxide release, with a half-maximal inhibition obtained with 14 nM phorbol 12,13-dibutyrate at saturating concentration of LPS. Incubation of cells with alpha-phorbol 12,13-didecanoate failed to counteract the effect of LPS or to induce nitric oxide synthase, suggesting that activation of protein kinase C was involved in this process."} {"id": "PMID:1281152", "title": "Alternative splicing of the Oct-2 transcription factor RNA is differentially regulated in neuronal cells and B cells and results in protein isoforms with opposite effects on the activity of octamer/TAATGARAT-containing promoters.", "content": "The RNA encoding the octamer-binding transcription factor Oct-2 is alternatively spliced in both neuronal cells and in B cells to yield multiple mRNAs encoding different isoforms of the protein. We show that, compared with B cells, neuronal cells overexpress the mRNAs encoding Oct 2.4 and 2.5 which differ from the other forms (Oct 2.1, 2.2, and 2.3) at the C terminus of the protein. When introduced into cells lacking endogenous Oct-2, the various Oct-2 isoforms have different effects on octamer-containing promoters. The Oct 2.1, 2.2, and 2.3 forms stimulate all octamer-containing promoters. However, the Oct 2.4 and 2.5 forms can repress some promoters and stimulate others, depending on the sequence of the octamer motif and its context within the promoter. In contrast, when introduced into neuronal cells which express a high endogenous level of the inhibitory Oct 2.4 and 2.5 forms, all the Oct-2 isoforms can repress octamer-mediated gene expression. The significance of these findings is discussed with regard to the known inhibitory effect of the octamer motif on viral and cellular gene expression in neuronal cells.", "contents": "Alternative splicing of the Oct-2 transcription factor RNA is differentially regulated in neuronal cells and B cells and results in protein isoforms with opposite effects on the activity of octamer/TAATGARAT-containing promoters. The RNA encoding the octamer-binding transcription factor Oct-2 is alternatively spliced in both neuronal cells and in B cells to yield multiple mRNAs encoding different isoforms of the protein. We show that, compared with B cells, neuronal cells overexpress the mRNAs encoding Oct 2.4 and 2.5 which differ from the other forms (Oct 2.1, 2.2, and 2.3) at the C terminus of the protein. When introduced into cells lacking endogenous Oct-2, the various Oct-2 isoforms have different effects on octamer-containing promoters. The Oct 2.1, 2.2, and 2.3 forms stimulate all octamer-containing promoters. However, the Oct 2.4 and 2.5 forms can repress some promoters and stimulate others, depending on the sequence of the octamer motif and its context within the promoter. In contrast, when introduced into neuronal cells which express a high endogenous level of the inhibitory Oct 2.4 and 2.5 forms, all the Oct-2 isoforms can repress octamer-mediated gene expression. The significance of these findings is discussed with regard to the known inhibitory effect of the octamer motif on viral and cellular gene expression in neuronal cells."} {"id": "PMID:1281153", "title": "Beta-L-thymidine 5'-triphosphate analogs as DNA polymerase substrates.", "content": "beta-L-3'-Deoxythymidine 5'-triphosphate (L-ddTTP) and beta-L-3'-deoxy-2',3'-didehydrothymidine 5'-triphosphate (L-d4TTP) were substrates for human immunodeficiency virus reverse transcriptase, Escherichia coli DNA polymerase I (Klenow), and Sequenase (modified T7 DNA polymerase). The beta-D- and beta-L-enantiomers of 5-methyluridine 5'-triphosphate (rTTP) were inhibitors but not substrates of reverse transcriptase. The steady-state Km values for L-ddTTP and L-d4TTP, with all three enzymes, were 12-70-fold larger than the Km values for the corresponding D-enantiomers. The Km value of reverse transcriptase for L-ddTTP was 50-fold larger than that for D-ddTTP because the Kd for L-ddTTP was 5-fold larger than that for D-ddTTP, and the first-order rate constant for incorporation of L-ddTMP into the template-primer was 10% that of the D-enantiomer. The D- and L-enantiomers had kcat values with reverse transcriptase and Sequenase that were similar to kcat for the natural substrate, thymidine 5'-triphosphate (dTTP). Thus, the rate determining step appeared to be dissociation of the enzyme-chain-terminated template-primer complex. In contrast, kcat values for the L-enantiomers with Klenow were only 0.1% that of dTTP, and the kcat values for the D-enantiomers were 15% the kcat for dTTP. The reduced kcat values were due to a change in rate determining step from dissociation of the Klenow-chain-terminated template-primer complex to an earlier step in the reaction mechanism, presumably catalysis. Thus, these DNA polymerases did not stereospecifically recognize D-nucleoside 5'-triphosphate analogs as substrates.", "contents": "Beta-L-thymidine 5'-triphosphate analogs as DNA polymerase substrates. beta-L-3'-Deoxythymidine 5'-triphosphate (L-ddTTP) and beta-L-3'-deoxy-2',3'-didehydrothymidine 5'-triphosphate (L-d4TTP) were substrates for human immunodeficiency virus reverse transcriptase, Escherichia coli DNA polymerase I (Klenow), and Sequenase (modified T7 DNA polymerase). The beta-D- and beta-L-enantiomers of 5-methyluridine 5'-triphosphate (rTTP) were inhibitors but not substrates of reverse transcriptase. The steady-state Km values for L-ddTTP and L-d4TTP, with all three enzymes, were 12-70-fold larger than the Km values for the corresponding D-enantiomers. The Km value of reverse transcriptase for L-ddTTP was 50-fold larger than that for D-ddTTP because the Kd for L-ddTTP was 5-fold larger than that for D-ddTTP, and the first-order rate constant for incorporation of L-ddTMP into the template-primer was 10% that of the D-enantiomer. The D- and L-enantiomers had kcat values with reverse transcriptase and Sequenase that were similar to kcat for the natural substrate, thymidine 5'-triphosphate (dTTP). Thus, the rate determining step appeared to be dissociation of the enzyme-chain-terminated template-primer complex. In contrast, kcat values for the L-enantiomers with Klenow were only 0.1% that of dTTP, and the kcat values for the D-enantiomers were 15% the kcat for dTTP. The reduced kcat values were due to a change in rate determining step from dissociation of the Klenow-chain-terminated template-primer complex to an earlier step in the reaction mechanism, presumably catalysis. Thus, these DNA polymerases did not stereospecifically recognize D-nucleoside 5'-triphosphate analogs as substrates."} {"id": "PMID:1281154", "title": "The dual role of the cAMP-dependent protein kinase C alpha subunit in T-cell receptor-triggered T-lymphocytes effector functions.", "content": "In order to directly evaluate the role of the cAMP-dependent protein kinase (PKA) catalytic (C) subunit in T-cell receptor- (TCR) triggered cytotoxic T-lymphocytes (CTL) effector functions, cells were studied after pretreatment with antisense oligomers complementary to mRNA for the C alpha or C beta subunits. C alpha subunit is shown to be predominantly expressed in CTL. In some experiments the pretreatment of the CTL with the C alpha antisense, but not with the control or C beta antisense oligomers, resulted in the inhibition of cAMP-independent PKA activity without significantly affecting the level of total cAMP-inducible PKA activity. In parallel assays, CTL which were pretreated with the C alpha antisense oligomer had enhanced antigen-bearing target cell-triggered-, anti-TCR monoclonal antibody-triggered-, and phorbol 12-myristate 13-acetate/A23187-triggered exocytosis of granules, as well as enhanced antigen-specific cytotoxicity. In contrast, the TCR-triggered gamma-interferon mRNA expression and gamma-interferon secretion were inhibited in C alpha antisense-pretreated CTL. These results suggest that the C alpha subunit of PKA may have a dual role in regulation of T-lymphocytes effector functions: (i) it may down-regulate TCR-triggered protein-synthesis independent responses such as cytotoxicity and exocytosis, thereby counteracting TCR-triggered activation even in the absence of the second messenger, cAMP, and (ii) the C alpha subunit activity is likely to be required for the nuclear and/or cytoplasmic events in CTL's activation involved in lymphokine synthesis and secretion.", "contents": "The dual role of the cAMP-dependent protein kinase C alpha subunit in T-cell receptor-triggered T-lymphocytes effector functions. In order to directly evaluate the role of the cAMP-dependent protein kinase (PKA) catalytic (C) subunit in T-cell receptor- (TCR) triggered cytotoxic T-lymphocytes (CTL) effector functions, cells were studied after pretreatment with antisense oligomers complementary to mRNA for the C alpha or C beta subunits. C alpha subunit is shown to be predominantly expressed in CTL. In some experiments the pretreatment of the CTL with the C alpha antisense, but not with the control or C beta antisense oligomers, resulted in the inhibition of cAMP-independent PKA activity without significantly affecting the level of total cAMP-inducible PKA activity. In parallel assays, CTL which were pretreated with the C alpha antisense oligomer had enhanced antigen-bearing target cell-triggered-, anti-TCR monoclonal antibody-triggered-, and phorbol 12-myristate 13-acetate/A23187-triggered exocytosis of granules, as well as enhanced antigen-specific cytotoxicity. In contrast, the TCR-triggered gamma-interferon mRNA expression and gamma-interferon secretion were inhibited in C alpha antisense-pretreated CTL. These results suggest that the C alpha subunit of PKA may have a dual role in regulation of T-lymphocytes effector functions: (i) it may down-regulate TCR-triggered protein-synthesis independent responses such as cytotoxicity and exocytosis, thereby counteracting TCR-triggered activation even in the absence of the second messenger, cAMP, and (ii) the C alpha subunit activity is likely to be required for the nuclear and/or cytoplasmic events in CTL's activation involved in lymphokine synthesis and secretion."} {"id": "PMID:1281155", "title": "Post-translational processing of the leukocyte integrin alpha 4 beta 1.", "content": "The leukocyte integrin alpha 4 beta 1 (VLA-4, CD49d/CD29) is a receptor for the extracellular matrix protein fibronectin and the endothelial adhesion protein VCAM-1. We have analyzed the biosynthesis and post-translational modifications of the two subunits of this receptor complex. The alpha 4 subunit was initially synthesized as a single-chain polypeptide that underwent the formation of complex endoglycosidase H-resistant oligosaccharide side chains and which could be proteolytically cleaved into two noncovalently associated fragments. The level and rate of alpha 4 subunit cleavage was dependent on the cell studied. The T cell tumor line HPB-ALL expressed both intact and fragmented alpha 4 on the cell surface. The interleukin-2-dependent natural killer line NK 3.3 and long term interleukin-2-dependent activated T lymphocytes cleaved the alpha 4 polypeptide earlier and more efficiently than did HPB-ALL cells and did not have detectable levels of intact alpha 4 on the cell surface. The proteolysis of alpha 4 was blocked by treating cells with either the lysosomotrophic amine NH4Cl or the carboxylic ionophore monensin. The presence of complex N-linked oligosaccharides did not seem to be necessary for alpha 4 cleavage or for binding of the alpha 4 beta 1 complex to a synthetic peptide corresponding to the binding site for this receptor on fibronectin.", "contents": "Post-translational processing of the leukocyte integrin alpha 4 beta 1. The leukocyte integrin alpha 4 beta 1 (VLA-4, CD49d/CD29) is a receptor for the extracellular matrix protein fibronectin and the endothelial adhesion protein VCAM-1. We have analyzed the biosynthesis and post-translational modifications of the two subunits of this receptor complex. The alpha 4 subunit was initially synthesized as a single-chain polypeptide that underwent the formation of complex endoglycosidase H-resistant oligosaccharide side chains and which could be proteolytically cleaved into two noncovalently associated fragments. The level and rate of alpha 4 subunit cleavage was dependent on the cell studied. The T cell tumor line HPB-ALL expressed both intact and fragmented alpha 4 on the cell surface. The interleukin-2-dependent natural killer line NK 3.3 and long term interleukin-2-dependent activated T lymphocytes cleaved the alpha 4 polypeptide earlier and more efficiently than did HPB-ALL cells and did not have detectable levels of intact alpha 4 on the cell surface. The proteolysis of alpha 4 was blocked by treating cells with either the lysosomotrophic amine NH4Cl or the carboxylic ionophore monensin. The presence of complex N-linked oligosaccharides did not seem to be necessary for alpha 4 cleavage or for binding of the alpha 4 beta 1 complex to a synthetic peptide corresponding to the binding site for this receptor on fibronectin."} {"id": "PMID:1281156", "title": "Release of transforming growth factor-beta 1 from the pericellular matrix of cultured fibroblasts and fibrosarcoma cells by plasmin and thrombin.", "content": "A sensitive immunoblotting assay was developed for the detection of transforming growth factor (TGF)-beta 1 from cell extracts and culture medium. HT-1080 human fibrosarcoma cells and human fibroblasts were used as models for the secretion and proteolytic release of pericellular matrix-associated TGF-beta 1. Analysis of the pericellular matrices of the cells indicated that the majority of cell-layer associated TGF-beta 1 was associated with the pericellular matrix. Treatment of the cells with plasmin or thrombin released the matrix-associated TGF-beta 1 to the culture medium. Assays for the biological activity of plasmin-released TGF-beta 1 by Mv1Lu cell growth inhibition assays indicated that the majority was in the latent form. Northern hybridization analyses indicated that the mRNA levels of TGF-beta 1 were not elevated during the proteinase treatment. Experiments using radiolabeled TGF-beta 1 indicated that exogenous active TGF-beta 1 associates mainly with the presumed TGF-beta 1 receptors that were not retained in the extracellular matrix preparations. These results indicate that a major fraction of latent TGF-beta 1 that is produced by the cells is deposited to and remains associated with the pericellular matrices of cultured fibroblasts and fibrosarcoma cells, and that matrix-associated TGF-beta 1 is very susceptible to release by various proteolytic enzymes.", "contents": "Release of transforming growth factor-beta 1 from the pericellular matrix of cultured fibroblasts and fibrosarcoma cells by plasmin and thrombin. A sensitive immunoblotting assay was developed for the detection of transforming growth factor (TGF)-beta 1 from cell extracts and culture medium. HT-1080 human fibrosarcoma cells and human fibroblasts were used as models for the secretion and proteolytic release of pericellular matrix-associated TGF-beta 1. Analysis of the pericellular matrices of the cells indicated that the majority of cell-layer associated TGF-beta 1 was associated with the pericellular matrix. Treatment of the cells with plasmin or thrombin released the matrix-associated TGF-beta 1 to the culture medium. Assays for the biological activity of plasmin-released TGF-beta 1 by Mv1Lu cell growth inhibition assays indicated that the majority was in the latent form. Northern hybridization analyses indicated that the mRNA levels of TGF-beta 1 were not elevated during the proteinase treatment. Experiments using radiolabeled TGF-beta 1 indicated that exogenous active TGF-beta 1 associates mainly with the presumed TGF-beta 1 receptors that were not retained in the extracellular matrix preparations. These results indicate that a major fraction of latent TGF-beta 1 that is produced by the cells is deposited to and remains associated with the pericellular matrices of cultured fibroblasts and fibrosarcoma cells, and that matrix-associated TGF-beta 1 is very susceptible to release by various proteolytic enzymes."} {"id": "PMID:1281157", "title": "Identification of inducible calmodulin-dependent nitric oxide synthase in the liver of rats.", "content": "A calmodulin-dependent nitric oxide synthase was significantly induced in the liver of rats treated intravenously with heat-killed Propionibacterium acnes and 5 days later with Escherichia coli lipopolysaccharide. The apparent calmodulin-dependent and -independent isozymes were separated by Mono Q column chromatography after their partial purification by 2',5'-ADP-agarose affinity chromatography. Both enzymes had a molecular weight of 125,000 as determined by SDS-polyacrylamide gel electrophoresis and required NADPH, tetrahydrobiopterin, and dithiothreitol as cofactors. Their activities were completely inhibited by the specific nitric oxide synthase inhibitors NG-monomethyl-L-arginine and N omega-nitro-L-arginine at 80 and 800 microM, respectively. The peptide maps of these two isozymes with lysylendopeptidase and their reverse-phase column chromatographic profiles were indistinguishable. In the presence of bovine calmodulin, the purified calmodulin-dependent isozyme behaved as a calmodulin-independent isozyme on Mono Q column chromatography. The purified calmodulin-independent isozyme was converted to a calmodulin-dependent isozyme by EDTA and EGTA. Calmodulin blot analysis using 125I-calmodulin showed that the two isozymes bound calmodulin equally efficiently.", "contents": "Identification of inducible calmodulin-dependent nitric oxide synthase in the liver of rats. A calmodulin-dependent nitric oxide synthase was significantly induced in the liver of rats treated intravenously with heat-killed Propionibacterium acnes and 5 days later with Escherichia coli lipopolysaccharide. The apparent calmodulin-dependent and -independent isozymes were separated by Mono Q column chromatography after their partial purification by 2',5'-ADP-agarose affinity chromatography. Both enzymes had a molecular weight of 125,000 as determined by SDS-polyacrylamide gel electrophoresis and required NADPH, tetrahydrobiopterin, and dithiothreitol as cofactors. Their activities were completely inhibited by the specific nitric oxide synthase inhibitors NG-monomethyl-L-arginine and N omega-nitro-L-arginine at 80 and 800 microM, respectively. The peptide maps of these two isozymes with lysylendopeptidase and their reverse-phase column chromatographic profiles were indistinguishable. In the presence of bovine calmodulin, the purified calmodulin-dependent isozyme behaved as a calmodulin-independent isozyme on Mono Q column chromatography. The purified calmodulin-independent isozyme was converted to a calmodulin-dependent isozyme by EDTA and EGTA. Calmodulin blot analysis using 125I-calmodulin showed that the two isozymes bound calmodulin equally efficiently."} {"id": "PMID:1281158", "title": "Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity.", "content": "Interleukin-8 (IL-8) is a key mediator in the migration of neutrophils from the circulation to the site of inflammation in the tissue. IL-8 is secreted by many cell types in response to proinflammatory stimuli such as interleukin 1, tumor necrosis factor, and lipopolysaccharide and is a potent chemoattractant and activator of neutrophils. Neutrophil activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA/GRO) are structurally and functionally related to IL-8 and, like IL-8, bind to specific G protein-coupled receptors on neutrophils. In the present study two closely related cloned IL-8 receptor subtypes are characterized by expression of the cDNA clones in monkey kidney cells (COS-7) or chinese hamster ovary cells and analysis of their ligand binding profiles. Both receptor subtypes bind 125I-labeled IL-8 with similar high affinity, however, the F3R receptor binds IL-8 exclusively, while the 4Ab receptor binds both IL-8 and MGSA/GRO with high affinity and NAP-2 with lesser affinity. Furthermore, we demonstrate with the use of intersubtype chimeric receptors that the specificity of ligand binding to both IL-8 receptor subtypes is dictated by the heterogeneous NH2-terminal domain. The F3R receptor is representative of a restricted IL-8 receptor subtype, and 4Ab represents a nonrestricted receptor subtype. It is proposed that these subtypes be named IL-8 receptors alpha and beta, respectively.", "contents": "Amino terminus of the interleukin-8 receptor is a major determinant of receptor subtype specificity. Interleukin-8 (IL-8) is a key mediator in the migration of neutrophils from the circulation to the site of inflammation in the tissue. IL-8 is secreted by many cell types in response to proinflammatory stimuli such as interleukin 1, tumor necrosis factor, and lipopolysaccharide and is a potent chemoattractant and activator of neutrophils. Neutrophil activating peptide-2 (NAP-2) and melanoma growth-stimulatory activity (MGSA/GRO) are structurally and functionally related to IL-8 and, like IL-8, bind to specific G protein-coupled receptors on neutrophils. In the present study two closely related cloned IL-8 receptor subtypes are characterized by expression of the cDNA clones in monkey kidney cells (COS-7) or chinese hamster ovary cells and analysis of their ligand binding profiles. Both receptor subtypes bind 125I-labeled IL-8 with similar high affinity, however, the F3R receptor binds IL-8 exclusively, while the 4Ab receptor binds both IL-8 and MGSA/GRO with high affinity and NAP-2 with lesser affinity. Furthermore, we demonstrate with the use of intersubtype chimeric receptors that the specificity of ligand binding to both IL-8 receptor subtypes is dictated by the heterogeneous NH2-terminal domain. The F3R receptor is representative of a restricted IL-8 receptor subtype, and 4Ab represents a nonrestricted receptor subtype. It is proposed that these subtypes be named IL-8 receptors alpha and beta, respectively."} {"id": "PMID:1281159", "title": "The Na-K-Cl cotransporter of avian salt gland. Phosphorylation in response to cAMP-dependent and calcium-dependent secretogogues.", "content": "The effect of a cAMP-dependent secretogogue (VIP) on the phosphorylation of an endogenous, membrane-bound protein (pp170) was assessed in an intact cell preparation from the avian salt gland. The addition of VIP, in the presence of 100 microM isobutylmethylxanthine, resulted in a concentration-dependent increase in phosphorylation of pp170. This effect was rapid and transient with a 3-5-fold increase in phosphorylation occurring 1 min after the addition of VIP. Under similar incubation conditions, VIP stimulated a 4.6-fold increase in cAMP accumulation that paralleled phosphorylation. Exposure of cells to either forskolin or 8-Br-cAMP resulted in a 5-8-fold increase in the phosphorylation of pp170. The effect of forskolin was dose dependent with an EC50 similar to that for stimulation of secretion (35 nM). These results implicate an involvement for a cAMP-dependent protein kinase in the phosphorylation of pp170. The identity of pp170 was assessed utilizing a monoclonal antibody (Q3) directed against pp170. Q3 recognized a single 170-kDa band on Western blots of salt gland membrane protein. Immunoprecipitation of pp170 from salt gland cells resulted in the selective extraction of a single protein whose phosphorylation state was increased approximately 5-fold in response to carbachol or VIP. The identity of pp170 was established using two criteria. First, Q3 recognized affinity-purified Na:K:Cl cotransporter preparations from shark rectal gland membranes. Second, pp170 was selectively immunoprecipitated by monoclonal antibodies (J3, J4, and J7) that recognize different epitopes of the shark transport protein. These results suggest that pp170 is homologous to the shark rectal gland Na-K-Cl cotransporter, and thus the proteins may be functionally similar.", "contents": "The Na-K-Cl cotransporter of avian salt gland. Phosphorylation in response to cAMP-dependent and calcium-dependent secretogogues. The effect of a cAMP-dependent secretogogue (VIP) on the phosphorylation of an endogenous, membrane-bound protein (pp170) was assessed in an intact cell preparation from the avian salt gland. The addition of VIP, in the presence of 100 microM isobutylmethylxanthine, resulted in a concentration-dependent increase in phosphorylation of pp170. This effect was rapid and transient with a 3-5-fold increase in phosphorylation occurring 1 min after the addition of VIP. Under similar incubation conditions, VIP stimulated a 4.6-fold increase in cAMP accumulation that paralleled phosphorylation. Exposure of cells to either forskolin or 8-Br-cAMP resulted in a 5-8-fold increase in the phosphorylation of pp170. The effect of forskolin was dose dependent with an EC50 similar to that for stimulation of secretion (35 nM). These results implicate an involvement for a cAMP-dependent protein kinase in the phosphorylation of pp170. The identity of pp170 was assessed utilizing a monoclonal antibody (Q3) directed against pp170. Q3 recognized a single 170-kDa band on Western blots of salt gland membrane protein. Immunoprecipitation of pp170 from salt gland cells resulted in the selective extraction of a single protein whose phosphorylation state was increased approximately 5-fold in response to carbachol or VIP. The identity of pp170 was established using two criteria. First, Q3 recognized affinity-purified Na:K:Cl cotransporter preparations from shark rectal gland membranes. Second, pp170 was selectively immunoprecipitated by monoclonal antibodies (J3, J4, and J7) that recognize different epitopes of the shark transport protein. These results suggest that pp170 is homologous to the shark rectal gland Na-K-Cl cotransporter, and thus the proteins may be functionally similar."} {"id": "PMID:1281160", "title": "Measurement of intracellular cadmium with fluorescent dyes. Further evidence for the role of calcium channels in cadmium uptake.", "content": "Cellular uptake of Cd2+ has been monitored using intracellularly trapped dyes, Fura 2 and Quin 2, which bind Cd2+ with extremely high affinity, and digital fluorescence imaging has been used to visualize intracellular free Cd2+. The excitation spectrum of the Cd2+ complex of Fura 2 is similar to that of the Ca2+ complex, whereas Cd2+ displaces Ca2+ from Quin 2 and reduces fluorescence. Fluorescence of Fura 2-loaded cells increased when 50 microM extracellular Cd2+ was added and fluorescence of Quin 2-loaded cells decreased. Cd2+ uptake by GH3 pituitary cells, which occurs in part via voltage-sensitive L-type calcium channels, was increased by BAY K8644 and depolarization and decreased by nimodipine. When Fura 2 and Quin 2 were used to measure Cd2+ uptake by glial C6 cells, which have no L-channel activity, high K+ and BAY K8644 did not change the apparent rate of Cd2+ uptake. GH3 and C6 cells were incubated with Cd2+ for 24 h and loaded with Fura 2, and fluorescence was measured before and after addition of tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN), a membrane permeant chelator with extremely high affinity for metals. TPEN had little effect on fluorescence of Fura 2-loaded GH3 and C6 cells not exposed to Cd2+ but decreased fluorescence of cells that had been incubated with 1-10 microM Cd2+. Fluorescence ratio imaging of Fura 2-loaded cells was used to image intracellular free Cd2+ for both GH3 and C6 cells. Cd2+ uptake over 30-180 min could be followed by the increase in 340/380 fluorescence ratio and the increase in fluorescence ratio was reversed within 5 min by TPEN. The results provide further evidence for the importance of voltage-gated calcium channels to Cd2+ uptake of certain cells.", "contents": "Measurement of intracellular cadmium with fluorescent dyes. Further evidence for the role of calcium channels in cadmium uptake. Cellular uptake of Cd2+ has been monitored using intracellularly trapped dyes, Fura 2 and Quin 2, which bind Cd2+ with extremely high affinity, and digital fluorescence imaging has been used to visualize intracellular free Cd2+. The excitation spectrum of the Cd2+ complex of Fura 2 is similar to that of the Ca2+ complex, whereas Cd2+ displaces Ca2+ from Quin 2 and reduces fluorescence. Fluorescence of Fura 2-loaded cells increased when 50 microM extracellular Cd2+ was added and fluorescence of Quin 2-loaded cells decreased. Cd2+ uptake by GH3 pituitary cells, which occurs in part via voltage-sensitive L-type calcium channels, was increased by BAY K8644 and depolarization and decreased by nimodipine. When Fura 2 and Quin 2 were used to measure Cd2+ uptake by glial C6 cells, which have no L-channel activity, high K+ and BAY K8644 did not change the apparent rate of Cd2+ uptake. GH3 and C6 cells were incubated with Cd2+ for 24 h and loaded with Fura 2, and fluorescence was measured before and after addition of tetrakis-(2-pyridylmethyl)ethylenediamine (TPEN), a membrane permeant chelator with extremely high affinity for metals. TPEN had little effect on fluorescence of Fura 2-loaded GH3 and C6 cells not exposed to Cd2+ but decreased fluorescence of cells that had been incubated with 1-10 microM Cd2+. Fluorescence ratio imaging of Fura 2-loaded cells was used to image intracellular free Cd2+ for both GH3 and C6 cells. Cd2+ uptake over 30-180 min could be followed by the increase in 340/380 fluorescence ratio and the increase in fluorescence ratio was reversed within 5 min by TPEN. The results provide further evidence for the importance of voltage-gated calcium channels to Cd2+ uptake of certain cells."} {"id": "PMID:1281161", "title": "Characterization of insulin-like growth factor (IGF) binding proteins and their role in modulating IGF-I action in BHK cells.", "content": "We have found that over one-half of the total cell surface 125I-insulin-like growth factor I (IGF-I) binding to BHK cells represents binding to IGF binding proteins (IGFBPs) rather than to the IGF-I receptor. In addition to a number of secreted IGFBPs, we have now characterized two cell-associated IGFBPs with unique characteristics. The cell-associated IGFBPs have molecular weights of 30,000 (30K) and 25,000 (25K), as determined by the Western ligand blot technique. IGFBP-30K is located at the cell surface and can be readily labeled by affinity cross-linking with 125I-IGF-I. Surface expression of IGFBP-30K increases 5.4 +/- 1.2-fold (n = 11) with serum starvation. This induction is fully evident by 4 h, plateauing by 24 h, and is completely inhibitable by cycloheximide. The fasting-induced increase in IGFBP-30K is inhibited by IGF-I and by des-IGF-I and, to a lesser extent, by insulin. Unlike cell-associated IGFBP-30K, secretion of IGFBP was stimulated (6.8 +/- 0.5-fold, n = 2) by IGF-I, whereas IGFBP secretion was inhibited 54% by insulin. These results demonstrate coordinate regulation of IGFBP by serum starvation and IGF-I, such that at low concentrations of IGF-I, cell surface binding protein increases whereas binding protein secretion decreases. At high concentrations of IGF-I, IGFBP secretion increases and cell surface IGF-I receptor, as well as IGFBP, decreases. Taken together, these regulatory events regulate the availability of IGF-I for biologic signalling.", "contents": "Characterization of insulin-like growth factor (IGF) binding proteins and their role in modulating IGF-I action in BHK cells. We have found that over one-half of the total cell surface 125I-insulin-like growth factor I (IGF-I) binding to BHK cells represents binding to IGF binding proteins (IGFBPs) rather than to the IGF-I receptor. In addition to a number of secreted IGFBPs, we have now characterized two cell-associated IGFBPs with unique characteristics. The cell-associated IGFBPs have molecular weights of 30,000 (30K) and 25,000 (25K), as determined by the Western ligand blot technique. IGFBP-30K is located at the cell surface and can be readily labeled by affinity cross-linking with 125I-IGF-I. Surface expression of IGFBP-30K increases 5.4 +/- 1.2-fold (n = 11) with serum starvation. This induction is fully evident by 4 h, plateauing by 24 h, and is completely inhibitable by cycloheximide. The fasting-induced increase in IGFBP-30K is inhibited by IGF-I and by des-IGF-I and, to a lesser extent, by insulin. Unlike cell-associated IGFBP-30K, secretion of IGFBP was stimulated (6.8 +/- 0.5-fold, n = 2) by IGF-I, whereas IGFBP secretion was inhibited 54% by insulin. These results demonstrate coordinate regulation of IGFBP by serum starvation and IGF-I, such that at low concentrations of IGF-I, cell surface binding protein increases whereas binding protein secretion decreases. At high concentrations of IGF-I, IGFBP secretion increases and cell surface IGF-I receptor, as well as IGFBP, decreases. Taken together, these regulatory events regulate the availability of IGF-I for biologic signalling."} {"id": "PMID:1281162", "title": "Release of amino-terminal fragments from amyloid precursor protein reporter and mutated derivatives in cultured cells.", "content": "Abnormal proteolytic processing of amyloid precursor protein (APP) is thought to be central to the formation and deposition of beta amyloid peptide in Alzheimer's disease. A putative \"secretase\" activity normally releases an amino-terminal APP fragment by cleaving APP at residues within the beta amyloid peptide thereby precluding amyloidogenesis. In order to better understand the requirements for APP cleavage by secretase, we have expressed a modified cDNA construct representing the 751-amino acid isoform of APP (APP-REP) and mutated APP-REP proteins in cultured cells. Here, we show that: (a) APP-REP is predominantly associated with membranes; (b) intracellular turnover and processing of APP-REP is similar to that reported for the intact APP protein; (c) secretion appears unaltered by introduction of the glutamate to glutamine mutation found in the APP gene of patients suffering from hereditary cerebral hemorrhage with amyloidosis of Dutch origin; (d) a mutation in which the 18 juxtamembranous amino acids encompassing the secretase site are deleted also allows release of an amino-terminal fragment into the conditioned medium; and (e) kinetics of cleavage of APP-REP and its mutated derivatives are similar. These results indicate that the secretory cleavage of the extracellular amino-terminal fragments of APP-REP can occur in the presence of different novel juxtamembranous amino acid sequences.", "contents": "Release of amino-terminal fragments from amyloid precursor protein reporter and mutated derivatives in cultured cells. Abnormal proteolytic processing of amyloid precursor protein (APP) is thought to be central to the formation and deposition of beta amyloid peptide in Alzheimer's disease. A putative \"secretase\" activity normally releases an amino-terminal APP fragment by cleaving APP at residues within the beta amyloid peptide thereby precluding amyloidogenesis. In order to better understand the requirements for APP cleavage by secretase, we have expressed a modified cDNA construct representing the 751-amino acid isoform of APP (APP-REP) and mutated APP-REP proteins in cultured cells. Here, we show that: (a) APP-REP is predominantly associated with membranes; (b) intracellular turnover and processing of APP-REP is similar to that reported for the intact APP protein; (c) secretion appears unaltered by introduction of the glutamate to glutamine mutation found in the APP gene of patients suffering from hereditary cerebral hemorrhage with amyloidosis of Dutch origin; (d) a mutation in which the 18 juxtamembranous amino acids encompassing the secretase site are deleted also allows release of an amino-terminal fragment into the conditioned medium; and (e) kinetics of cleavage of APP-REP and its mutated derivatives are similar. These results indicate that the secretory cleavage of the extracellular amino-terminal fragments of APP-REP can occur in the presence of different novel juxtamembranous amino acid sequences."} {"id": "PMID:1281163", "title": "Giant sarcoplasmic reticulum vesicles: a study of membrane morphogenesis.", "content": "Rabbit sarcoplasmic reticulum vesicles were fused into giant proteoliposomes in a medium of 0.1 M KCl, 10 mM Tris-maleate, pH 7.0, 10 micrograms ml-1 antipain, 10 micrograms ml-1 leupeptin, 25 IU per ml Trasylol, 3 mM NaN3, 3.75% PEG 1500 and 3% DMSO by brief exposure to 37 degrees C, followed by incubation for 4 h at 25 degrees C. Approximately 5-10% of the sarcoplasmic reticulum elements underwent fusion, forming single-walled spherical vesicles of 1-25 microns diameter, in which the polarity of the native membrane was preserved. The Ca(2+)-stimulated ATPase activity remained essentially unchanged after fusion. On exposure to decavanadate in a Ca(2+)-free medium the spherical vesicles assumed a corrugated appearance with the formation of long ridges separated by deep furrows that eventually pinched off longitudinally and separated into numerous long crystalline tubules of uniform (approximately 0.1 microns) diameter. The vanadate-induced transformation of giant vesicles into tubules implies that the geometry of the sarcoplasmic reticulum membrane is determined by the conformation of the Ca(2+)-ATPase.", "contents": "Giant sarcoplasmic reticulum vesicles: a study of membrane morphogenesis. Rabbit sarcoplasmic reticulum vesicles were fused into giant proteoliposomes in a medium of 0.1 M KCl, 10 mM Tris-maleate, pH 7.0, 10 micrograms ml-1 antipain, 10 micrograms ml-1 leupeptin, 25 IU per ml Trasylol, 3 mM NaN3, 3.75% PEG 1500 and 3% DMSO by brief exposure to 37 degrees C, followed by incubation for 4 h at 25 degrees C. Approximately 5-10% of the sarcoplasmic reticulum elements underwent fusion, forming single-walled spherical vesicles of 1-25 microns diameter, in which the polarity of the native membrane was preserved. The Ca(2+)-stimulated ATPase activity remained essentially unchanged after fusion. On exposure to decavanadate in a Ca(2+)-free medium the spherical vesicles assumed a corrugated appearance with the formation of long ridges separated by deep furrows that eventually pinched off longitudinally and separated into numerous long crystalline tubules of uniform (approximately 0.1 microns) diameter. The vanadate-induced transformation of giant vesicles into tubules implies that the geometry of the sarcoplasmic reticulum membrane is determined by the conformation of the Ca(2+)-ATPase."} {"id": "PMID:1281164", "title": "S-100ab increases Ca2+ release in purified sarcoplasmic reticulum vesicles of frog skeletal muscle.", "content": "The S-100ab protein, a mixed isoform member of the S-100 family, stimulates Ca(2+)-induced Ca(2+)-release from sarcoplasmic reticulum vesicles purified from frog skeletal muscle cells. The effects of S-100ab appear to be specific and result from its peculiar characteristics rather than the fact that it is a calcium-binding protein. Moreover, the addition of S-100ab to the solution completely abolished the inhibition provoked when Ruthenium Red was added alone. Experiments that added labelled Ryanodine with and without S-100 indicated that the protein diminished the affinity of the alkaloid at its receptor site.", "contents": "S-100ab increases Ca2+ release in purified sarcoplasmic reticulum vesicles of frog skeletal muscle. The S-100ab protein, a mixed isoform member of the S-100 family, stimulates Ca(2+)-induced Ca(2+)-release from sarcoplasmic reticulum vesicles purified from frog skeletal muscle cells. The effects of S-100ab appear to be specific and result from its peculiar characteristics rather than the fact that it is a calcium-binding protein. Moreover, the addition of S-100ab to the solution completely abolished the inhibition provoked when Ruthenium Red was added alone. Experiments that added labelled Ryanodine with and without S-100 indicated that the protein diminished the affinity of the alkaloid at its receptor site."} {"id": "PMID:1281165", "title": "Synergy between encephalitogenic T cells and myelin basic protein-specific antibodies in the induction of experimental autoimmune encephalomyelitis.", "content": "Experimental autoimmune encephalomyelitis (EAE) is an experimentally induced demyelinating disease mediated by CD4+ T cells specific for various myelin proteins including myelin basic protein (MBP) and myelin proteolipid protein (PLP). Although myelin- and other CNS-specific antibodies are produced in EAE, B cells and antibodies are thought by most not to play a decisive role in the induction of EAE. In this report we show that B cells serve as the major antigen-presenting cells (APC) during the T cell activation stage in lymph nodes, and that MBP-specific antibodies can greatly enhance the induction of EAE. The role of B cells as APC is demonstrated in B cell-depleted mice. EAE cannot be induced by antigen/complete Freund's adjuvant immunization unless these mice are locally reconstituted with B cells prior to immunization. The enhancing effect of antibodies is demonstrated in experiments in which EAE is induced by the adoptive transfer of encephalitogenic T cells. The adoptive transfer of large numbers of encephalitogenic T cells induces EAE in 90% of normal recipient mice, but only 33% of B cell-depleted mice get EAE at the same cell dose. The efficiency of EAE induction in B cell-depleted mice can be enhanced if MBP-specific antibodies are simultaneously administered. A similar enhancement is also seen in normal mice when the number of adoptively transferred T cells is limiting. We propose that MBP-specific antibodies enhance the presentation of myelin-derived antigens by APC in the CNS to the adoptively transferred encephalitogenic T cells.", "contents": "Synergy between encephalitogenic T cells and myelin basic protein-specific antibodies in the induction of experimental autoimmune encephalomyelitis. Experimental autoimmune encephalomyelitis (EAE) is an experimentally induced demyelinating disease mediated by CD4+ T cells specific for various myelin proteins including myelin basic protein (MBP) and myelin proteolipid protein (PLP). Although myelin- and other CNS-specific antibodies are produced in EAE, B cells and antibodies are thought by most not to play a decisive role in the induction of EAE. In this report we show that B cells serve as the major antigen-presenting cells (APC) during the T cell activation stage in lymph nodes, and that MBP-specific antibodies can greatly enhance the induction of EAE. The role of B cells as APC is demonstrated in B cell-depleted mice. EAE cannot be induced by antigen/complete Freund's adjuvant immunization unless these mice are locally reconstituted with B cells prior to immunization. The enhancing effect of antibodies is demonstrated in experiments in which EAE is induced by the adoptive transfer of encephalitogenic T cells. The adoptive transfer of large numbers of encephalitogenic T cells induces EAE in 90% of normal recipient mice, but only 33% of B cell-depleted mice get EAE at the same cell dose. The efficiency of EAE induction in B cell-depleted mice can be enhanced if MBP-specific antibodies are simultaneously administered. A similar enhancement is also seen in normal mice when the number of adoptively transferred T cells is limiting. We propose that MBP-specific antibodies enhance the presentation of myelin-derived antigens by APC in the CNS to the adoptively transferred encephalitogenic T cells."} {"id": "PMID:1281166", "title": "Novel LCMV-specific H-2k restricted CTL clones recognize internal viral gene products and cause CNS disease.", "content": "H-2k (C3H/Hej) cytotoxic T lymphocytes (CTL) specific for lymphocytic choriomeningitis virus (LCMV) were cloned. Three clones recognizing internal viral antigens were studied. One such CTL clone recognized neither the glycoprotein nor nucleoprotein encoded by the viral short RNA segment, but reacted with a protein encoded by the long RNA segment, either the viral polymerase, or the Z protein. This one clone, in addition to primary CTL harvested from immunized C3H mice, failed to lyse target cells expressing the Z protein, suggesting recognition was to the viral polymerase. Two other clones recognized the viral nucleoprotein, amino acids 93-100, as determined by protein deletion and peptide mapping studies. When introduced directly into the central nervous systems of LCMV-infected histocompatible mice, all clones were active in vivo and capable of causing immunopathologically mediated death.", "contents": "Novel LCMV-specific H-2k restricted CTL clones recognize internal viral gene products and cause CNS disease. H-2k (C3H/Hej) cytotoxic T lymphocytes (CTL) specific for lymphocytic choriomeningitis virus (LCMV) were cloned. Three clones recognizing internal viral antigens were studied. One such CTL clone recognized neither the glycoprotein nor nucleoprotein encoded by the viral short RNA segment, but reacted with a protein encoded by the long RNA segment, either the viral polymerase, or the Z protein. This one clone, in addition to primary CTL harvested from immunized C3H mice, failed to lyse target cells expressing the Z protein, suggesting recognition was to the viral polymerase. Two other clones recognized the viral nucleoprotein, amino acids 93-100, as determined by protein deletion and peptide mapping studies. When introduced directly into the central nervous systems of LCMV-infected histocompatible mice, all clones were active in vivo and capable of causing immunopathologically mediated death."} {"id": "PMID:1281167", "title": "Peripheral nervous system (PNS) expression of mRNAs encoding myelin proteins and Fc gamma RIII during experimental allergic neuritis.", "content": "Experimental allergic neuritis (EAN) was induced in Lewis rats by injection of 'SP26', a peptide homologous to amino acids 53-78 of bovine myelin P2 protein, in complete Freund's adjuvant. The rats developed signs of EAN which began on day 14, were maximal on day 18, and had subsided by day 30. RNA content of cauda equina and sciatic nerves increased more than 2-fold at the height of EAN. Expression of myelin P0 and P1 mRNAs did not fall during EAN, nor rise during recovery. Fc gamma R mRNA, which encodes Fc gamma RIII, an immunoglobulin-binding protein mediating activation of natural killer cells and macrophages by immune complexes, was transiently, but markedly induced in scattered endoneural cells, presumably macrophages, in cauda equina and sciatic nerves during the period of increasing weakness.", "contents": "Peripheral nervous system (PNS) expression of mRNAs encoding myelin proteins and Fc gamma RIII during experimental allergic neuritis. Experimental allergic neuritis (EAN) was induced in Lewis rats by injection of 'SP26', a peptide homologous to amino acids 53-78 of bovine myelin P2 protein, in complete Freund's adjuvant. The rats developed signs of EAN which began on day 14, were maximal on day 18, and had subsided by day 30. RNA content of cauda equina and sciatic nerves increased more than 2-fold at the height of EAN. Expression of myelin P0 and P1 mRNAs did not fall during EAN, nor rise during recovery. Fc gamma R mRNA, which encodes Fc gamma RIII, an immunoglobulin-binding protein mediating activation of natural killer cells and macrophages by immune complexes, was transiently, but markedly induced in scattered endoneural cells, presumably macrophages, in cauda equina and sciatic nerves during the period of increasing weakness."} {"id": "PMID:1281168", "title": "Autoimmunoregulation: differential modulation of CD10/neutral endopeptidase 24.11 by tumor necrosis factor and neuropeptides.", "content": "Neutral endopeptidase (NEP) 24.11 appears to be an important enzyme in both vertebrate and invertebrate autoimmunoregulation. Activation of human or invertebrate immunocytes that express NEP with substrates such as monokines and neuropeptides results in its increased expression, in other words, upregulation. However, since certain neuropeptides are also substrates for NEP, these activated immunocytes will respond to neuropeptides only at higher concentrations, thus downregulating the response. Specifically, in tumor necrosis factor (TNF)-treated immunocytes, we demonstrate the effects of increased NEP expression on altering the stimulatory activities of the neuropeptides met-enkephalin, melanocyte-stimulating hormone and substance P. We demonstrate the significance of NEP in modulating these responses through the use of specific enzyme inhibitors such as phosphoramidon, thiorphan and captopril. Furthermore, we present evidence suggesting that the individual variations seen in immunocytes from both different and the same donors to activating substances may reflect fluctuating levels of NEP expressed in response to endogenous stimuli. These results indicate that NEP is a highly significant factor in controlling the response(s) of certain immunocytes in man and higher invertebrates to the influence of biologically active substances such as monokines and neuropeptides.", "contents": "Autoimmunoregulation: differential modulation of CD10/neutral endopeptidase 24.11 by tumor necrosis factor and neuropeptides. Neutral endopeptidase (NEP) 24.11 appears to be an important enzyme in both vertebrate and invertebrate autoimmunoregulation. Activation of human or invertebrate immunocytes that express NEP with substrates such as monokines and neuropeptides results in its increased expression, in other words, upregulation. However, since certain neuropeptides are also substrates for NEP, these activated immunocytes will respond to neuropeptides only at higher concentrations, thus downregulating the response. Specifically, in tumor necrosis factor (TNF)-treated immunocytes, we demonstrate the effects of increased NEP expression on altering the stimulatory activities of the neuropeptides met-enkephalin, melanocyte-stimulating hormone and substance P. We demonstrate the significance of NEP in modulating these responses through the use of specific enzyme inhibitors such as phosphoramidon, thiorphan and captopril. Furthermore, we present evidence suggesting that the individual variations seen in immunocytes from both different and the same donors to activating substances may reflect fluctuating levels of NEP expressed in response to endogenous stimuli. These results indicate that NEP is a highly significant factor in controlling the response(s) of certain immunocytes in man and higher invertebrates to the influence of biologically active substances such as monokines and neuropeptides."} {"id": "PMID:1281169", "title": "Evidence for target tissue regulation of resistance to the induction of experimental allergic encephalomyelitis in AO rats.", "content": "A myelin basic protein (MBP)-specific T cell line derived from F1 hybrids between experimental allergic encephalomyelitis (EAE)-susceptible DA (RT1avl) strain and EAE-resistant AO (RT1u) strain was capable of inducing clinical EAE in F1 hybrids and DA, but not in AO rats. In vitro restimulation with MBP presented by AO antigen-presenting cells (APC) resulted in the generation of a MBP-specific subline restricted by RT1u MHC products which induced clinical EAE in F1 hybrids but not in the AO parental strain. Deletion of hosts' leukocytes using sublethal irradiation and cytotoxic drugs did not abrogate the resistance of AO rats, which argues against the involvement of hosts' lymphoid cells in the regulation of autoagression. Thus, mechanism(s) regulating the activity of autoagressive T cells on functional elements in the target tissue might be responsible for differences in susceptibility to EAE.", "contents": "Evidence for target tissue regulation of resistance to the induction of experimental allergic encephalomyelitis in AO rats. A myelin basic protein (MBP)-specific T cell line derived from F1 hybrids between experimental allergic encephalomyelitis (EAE)-susceptible DA (RT1avl) strain and EAE-resistant AO (RT1u) strain was capable of inducing clinical EAE in F1 hybrids and DA, but not in AO rats. In vitro restimulation with MBP presented by AO antigen-presenting cells (APC) resulted in the generation of a MBP-specific subline restricted by RT1u MHC products which induced clinical EAE in F1 hybrids but not in the AO parental strain. Deletion of hosts' leukocytes using sublethal irradiation and cytotoxic drugs did not abrogate the resistance of AO rats, which argues against the involvement of hosts' lymphoid cells in the regulation of autoagression. Thus, mechanism(s) regulating the activity of autoagressive T cells on functional elements in the target tissue might be responsible for differences in susceptibility to EAE."} {"id": "PMID:1281170", "title": "Afferent connections of the laterodorsal and the pedunculopontine tegmental nuclei in the rat: a retro- and antero-grade transport and immunohistochemical study.", "content": "Increasingly strong evidence suggests that cholinergic neurons in the mesopontine tegmentum play important roles in the control of wakefulness and sleep. To understand better how the activity of these neurons is regulated, the potential afferent connections of the laterodorsal (LDT) and pedunculopontine tegmental nuclei (PPT) were investigated in the rat. This was accomplished by using retrograde and anterograde axonal transport methods and NADPH-diaphorase histochemistry. Immunohistochemistry was also used to identify the transmitter content of some of the retrogradely identified afferents. Following injections of the retrograde tracer wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) into either the LDT or the PPT, labelled neurons were seen in a number of limbic forebrain structures. The medial prefrontal cortex and lateral habenula contained more retrogradely labelled neurons from the LDT, whereas in the bed nucleus of the stria terminalis and central nucleus of the amygdala, more cells were labelled from the PPT. Moderate numbers of neurons were seen in the magnocellular regions of the basal forebrain, and many labelled neurons were observed in the lateral hypothalamus, the zona incerta, and the midbrain central gray from both the LDT and the PPT. Accessory oculomotor nuclei in the midbrain as well as eye movement-related structures in the lower brainstem contained some neurons labelled from the LDT, and fewer neurons from the PPT. A few labelled neurons were seen in somatosensory and other sensory relay nuclei in the brainstem and the spinal cord. Retrograde labelling was seen in a number of extrapyramidal structures, including the globus pallidus, entopenduncular and subthalamic nuclei, and substantia nigra following PPT injections; with LDT injections, labelling was similar in density in the substantia nigra but virtually absent in the entopeduncular and subthalamic nuclei. Data with the fluorescent retrograde tracer fluorogold combined with immunofluorescence indicated that many neurons in the zona incerta-lateral hypothalamic region that were retrogradely labelled from the LDT contained alpha-melanocyte-stimulating hormone. Numerous neurons were labelled throughout the reticular formation of the brainstem following either LDT or PPT injections. Many neurons retrogradely labelled in the LDT and PPT, the dorsal and median raphe nuclei, and the locus ceruleus contained choline acetyltransferase, serotonin, and tyrosine hydroxylase, respectively. The anterograde tracers WGA-HRP and phaseolus vulgaris leucoagglutinin were used to confirm some of the projections indicated by the retrograde labelling data; anterograde labelling was seen in the LDT and PPT following injections of one of these tracers into the medial prefrontal cortex, lateral hypothalamus, and the contralateral LDT.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Afferent connections of the laterodorsal and the pedunculopontine tegmental nuclei in the rat: a retro- and antero-grade transport and immunohistochemical study. Increasingly strong evidence suggests that cholinergic neurons in the mesopontine tegmentum play important roles in the control of wakefulness and sleep. To understand better how the activity of these neurons is regulated, the potential afferent connections of the laterodorsal (LDT) and pedunculopontine tegmental nuclei (PPT) were investigated in the rat. This was accomplished by using retrograde and anterograde axonal transport methods and NADPH-diaphorase histochemistry. Immunohistochemistry was also used to identify the transmitter content of some of the retrogradely identified afferents. Following injections of the retrograde tracer wheatgerm agglutinin-conjugated horseradish peroxidase (WGA-HRP) into either the LDT or the PPT, labelled neurons were seen in a number of limbic forebrain structures. The medial prefrontal cortex and lateral habenula contained more retrogradely labelled neurons from the LDT, whereas in the bed nucleus of the stria terminalis and central nucleus of the amygdala, more cells were labelled from the PPT. Moderate numbers of neurons were seen in the magnocellular regions of the basal forebrain, and many labelled neurons were observed in the lateral hypothalamus, the zona incerta, and the midbrain central gray from both the LDT and the PPT. Accessory oculomotor nuclei in the midbrain as well as eye movement-related structures in the lower brainstem contained some neurons labelled from the LDT, and fewer neurons from the PPT. A few labelled neurons were seen in somatosensory and other sensory relay nuclei in the brainstem and the spinal cord. Retrograde labelling was seen in a number of extrapyramidal structures, including the globus pallidus, entopenduncular and subthalamic nuclei, and substantia nigra following PPT injections; with LDT injections, labelling was similar in density in the substantia nigra but virtually absent in the entopeduncular and subthalamic nuclei. Data with the fluorescent retrograde tracer fluorogold combined with immunofluorescence indicated that many neurons in the zona incerta-lateral hypothalamic region that were retrogradely labelled from the LDT contained alpha-melanocyte-stimulating hormone. Numerous neurons were labelled throughout the reticular formation of the brainstem following either LDT or PPT injections. Many neurons retrogradely labelled in the LDT and PPT, the dorsal and median raphe nuclei, and the locus ceruleus contained choline acetyltransferase, serotonin, and tyrosine hydroxylase, respectively. The anterograde tracers WGA-HRP and phaseolus vulgaris leucoagglutinin were used to confirm some of the projections indicated by the retrograde labelling data; anterograde labelling was seen in the LDT and PPT following injections of one of these tracers into the medial prefrontal cortex, lateral hypothalamus, and the contralateral LDT.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281171", "title": "Developmental differentiation of MAP2 expression in the central versus the peripheral and efferent projections of the inner ear.", "content": "The goal of this study was to extend our knowledge of MAP2 localization in the peripheral nervous system of mammals, since most results on MAP2 distribution are obtained in the central nervous system (CNS). This study shows the presence of microtubule-associated protein 2b (MAP2b) and MAP2c in the inner ear and describes the immunocytochemical distribution of MAP in adult and developing spiral ganglion of the rat by using a well-characterized antibody for MAP2a and MAP2b. (This antibody does not recognize the immature MAP2c). MAP2 labeling is already present in spiral ganglion neurons at 16 days of gestation. From this stage and up to the first postnatal week, MAP2 labeling was strong in all spiral ganglion neurons and their central processes. Double immunostaining at the 16-day stage with anti-MAP2 and anti-neurofilament (NF) antibodies mainly showed NF labeling in central branches that corresponded to anatomically and functionally described axons of spiral neurons. The peripheral branches lacked MAP2 labeling. In neonatal and postnatal stages, MAP2 reactivity was located in spiral ganglion perikarya and their neurites. The intensity of adult labeling was, however, lower than in younger animals. The antibody used in this study did not label axons originating in the CNS as seen by a negative response in efferent fibers from the intraganglionic spiral bundle of the cochlea. Our results suggest that during ontogenesis, MAP2 is highly expressed in the central projection of spiral ganglion neurons, and then is reduced to lower quantities in the central branch after the first postnatal week and persists into adulthood.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Developmental differentiation of MAP2 expression in the central versus the peripheral and efferent projections of the inner ear. The goal of this study was to extend our knowledge of MAP2 localization in the peripheral nervous system of mammals, since most results on MAP2 distribution are obtained in the central nervous system (CNS). This study shows the presence of microtubule-associated protein 2b (MAP2b) and MAP2c in the inner ear and describes the immunocytochemical distribution of MAP in adult and developing spiral ganglion of the rat by using a well-characterized antibody for MAP2a and MAP2b. (This antibody does not recognize the immature MAP2c). MAP2 labeling is already present in spiral ganglion neurons at 16 days of gestation. From this stage and up to the first postnatal week, MAP2 labeling was strong in all spiral ganglion neurons and their central processes. Double immunostaining at the 16-day stage with anti-MAP2 and anti-neurofilament (NF) antibodies mainly showed NF labeling in central branches that corresponded to anatomically and functionally described axons of spiral neurons. The peripheral branches lacked MAP2 labeling. In neonatal and postnatal stages, MAP2 reactivity was located in spiral ganglion perikarya and their neurites. The intensity of adult labeling was, however, lower than in younger animals. The antibody used in this study did not label axons originating in the CNS as seen by a negative response in efferent fibers from the intraganglionic spiral bundle of the cochlea. Our results suggest that during ontogenesis, MAP2 is highly expressed in the central projection of spiral ganglion neurons, and then is reduced to lower quantities in the central branch after the first postnatal week and persists into adulthood.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281172", "title": "Physiology and morphology of neurons in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract that are sensitive to distension of the small intestine.", "content": "We have recently shown that distension-sensitive vagal afferents are part of a neural circuit affecting absorption of water in the rat small intestine. Our results indicated that vagal afferent activity directly or indirectly influences the activity of neurons in the dorsal motor nucleus of the vagus (DMNV). In the present study we pursued this interaction by examining the structure and function of neurons in the DMNV and nucleus of the solitary tract (NST) that responded to moderate distension of the small intestine. Distension-sensitive cells were filled by intracellular iontophoretic injection of horseradish peroxidase. A total of 43 distension-sensitive brainstem neurons were successfully characterized and labeled. Sixteen of the 17 NST neurons were excited by distension of the small intestine. Ten of the seventeen were restricted to the ipsilateral NST. Only two NST neurons possessed axons that terminated in the subjacent DMNV. In contrast to the response profile of the NST neurons, 24 of 26 DMNV neurons were inhibited by intestinal distension. Fourteen of the DMNV neurons appeared to contribute to the vagus nerve and 15 extended dendrites into the overlying NST. We propose that distension-induced inhibition of DMNV activity is accomplished by inhibitory NST neurons, which synapse on the dendrites of DMNV neurons in the NST.", "contents": "Physiology and morphology of neurons in the dorsal motor nucleus of the vagus and the nucleus of the solitary tract that are sensitive to distension of the small intestine. We have recently shown that distension-sensitive vagal afferents are part of a neural circuit affecting absorption of water in the rat small intestine. Our results indicated that vagal afferent activity directly or indirectly influences the activity of neurons in the dorsal motor nucleus of the vagus (DMNV). In the present study we pursued this interaction by examining the structure and function of neurons in the DMNV and nucleus of the solitary tract (NST) that responded to moderate distension of the small intestine. Distension-sensitive cells were filled by intracellular iontophoretic injection of horseradish peroxidase. A total of 43 distension-sensitive brainstem neurons were successfully characterized and labeled. Sixteen of the 17 NST neurons were excited by distension of the small intestine. Ten of the seventeen were restricted to the ipsilateral NST. Only two NST neurons possessed axons that terminated in the subjacent DMNV. In contrast to the response profile of the NST neurons, 24 of 26 DMNV neurons were inhibited by intestinal distension. Fourteen of the DMNV neurons appeared to contribute to the vagus nerve and 15 extended dendrites into the overlying NST. We propose that distension-induced inhibition of DMNV activity is accomplished by inhibitory NST neurons, which synapse on the dendrites of DMNV neurons in the NST."} {"id": "PMID:1281173", "title": "Fine structure of rat septohippocampal neurons: I. Identification of septohippocampal projection neurons by retrograde tracing combined with electron microscopic immunocytochemistry and intracellular staining.", "content": "In this report the normal dendritic organization and fine structure of identified septohippocampal projection neurons is described as a prerequisite for a time course analysis of retrograde changes in these neurons following axotomy (see Naumann et al., J. Comp. Neurol. 325:219-242, 1992). Septohippocampal projection neurons were retrogradely labeled by injection of the fluorescent tracer Fluoro-Gold into the hippocampus. Next, retrogradely labeled cells in Vibratome sections of the medial septum/diagonal band complex were intracellularly stained with the fluorescent dye Lucifer Yellow (LY). Photooxidation of LY resulted in a stable electron-dense reaction product, which allowed us to study these double-labeled neurons by electron microscopy. Another series of sections containing retrogradely labeled neurons were immunostained for choline acetyltransferase (ChAT) or parvalbumin (PARV). In this way the fine structure of two different chemically characterized subpopulations of septohippocampal neurons could be compared with that of the LY-injected neurons. Intracellular filling of retrogradely labeled neurons with LY stained the cell body and the entire dendritic arbor. Essentially, three classes of neurons could be distinguished, i.e., bipolar cells, multipolar neurons, and an intermediate group. All these neurons displayed smooth, often varicose dendrites lacking spines. Mainly located close to the midline, there was a group of cells with only very few if any LY-stained dendrites. In the electron microscope, the double-labeled neurons were easily identified by numerous electron-dense lysosomes associated with transported Fluoro-Gold and the diffuse reaction product resulting from photooxidation. They displayed fine-structural characteristics as previously described for cholinergic neurons. In fact, our fine-structural analysis of ChAT-positive Fluoro-Gold-labeled neurons, but also of back-filled PARV-positive cells, gave very similar results. All these neurons had infolded nuclei, abundant cytoplasmic organelles, and a few axosomatic synapses. Thus, a plain electron microscopic study does not allow one to distinguish between subpopulations of septohippocampal projection neurons.", "contents": "Fine structure of rat septohippocampal neurons: I. Identification of septohippocampal projection neurons by retrograde tracing combined with electron microscopic immunocytochemistry and intracellular staining. In this report the normal dendritic organization and fine structure of identified septohippocampal projection neurons is described as a prerequisite for a time course analysis of retrograde changes in these neurons following axotomy (see Naumann et al., J. Comp. Neurol. 325:219-242, 1992). Septohippocampal projection neurons were retrogradely labeled by injection of the fluorescent tracer Fluoro-Gold into the hippocampus. Next, retrogradely labeled cells in Vibratome sections of the medial septum/diagonal band complex were intracellularly stained with the fluorescent dye Lucifer Yellow (LY). Photooxidation of LY resulted in a stable electron-dense reaction product, which allowed us to study these double-labeled neurons by electron microscopy. Another series of sections containing retrogradely labeled neurons were immunostained for choline acetyltransferase (ChAT) or parvalbumin (PARV). In this way the fine structure of two different chemically characterized subpopulations of septohippocampal neurons could be compared with that of the LY-injected neurons. Intracellular filling of retrogradely labeled neurons with LY stained the cell body and the entire dendritic arbor. Essentially, three classes of neurons could be distinguished, i.e., bipolar cells, multipolar neurons, and an intermediate group. All these neurons displayed smooth, often varicose dendrites lacking spines. Mainly located close to the midline, there was a group of cells with only very few if any LY-stained dendrites. In the electron microscope, the double-labeled neurons were easily identified by numerous electron-dense lysosomes associated with transported Fluoro-Gold and the diffuse reaction product resulting from photooxidation. They displayed fine-structural characteristics as previously described for cholinergic neurons. In fact, our fine-structural analysis of ChAT-positive Fluoro-Gold-labeled neurons, but also of back-filled PARV-positive cells, gave very similar results. All these neurons had infolded nuclei, abundant cytoplasmic organelles, and a few axosomatic synapses. Thus, a plain electron microscopic study does not allow one to distinguish between subpopulations of septohippocampal projection neurons."} {"id": "PMID:1281174", "title": "Distribution of the 275 kD hair cell antigen and cell surface specialisations on auditory and vestibular hair bundles in the chicken inner ear.", "content": "The 275 kD hair cell antigen (HCA) is a protein that is specifically associated with the apical surface of sensory hair cells in the chick inner ear. A comparative study of the vestibular and auditory organs of the inner ear, using both wholemounts and cryosections double labelled for the HCA and F-actin, reveals that two distinct types of hair cells can be distinguished on the basis of antibody staining in each of the vestibular epithelia. One type of hair cell has the HCA restricted to the base of the stereocilia bundle and is found in the striolae of the maculae and in a large, centrally located region of each ampulla. The other type of hair cell is found in the extrastriolar regions of the maculae and the peripheral regions of the ampullae and has the HCA distributed over the entire surface of the stereocilia bundle. In the basilar papilla, the auditory epithelium of the chick inner ear, the HCA is, as in the striolar regions of the maculae, restricted to the base of the hair bundles. In all sensory epithelia the HCA is also present on the apical, nonstereociliary surface of the hair cells. Ultrastructural examination of the basilar papilla and the striolar and the extrastriolar regions of the lagenar macula after staining with ruthenium red and tannic acid shows that there are four morphologically different types of interstereociliary connectors (oblique tip connectors, horizontal tip connectors, shaft connectors and basal connectors) associated with the hair bundles. Oblique tip connectors and basal connectors are found on hair cells from all regions and have a similar distribution. Horizontal tip connectors are seen only on hair cells in the basilar papilla and the striolar region of the lagenar macula. Shaft connectors extend all the way to the tips of extrastriolar hair cell bundles, but extend only a short way up the bundles of hair cells in the basilar papilla and striolar region of the lagenar macula. Immunogold labelling confirms the results obtained with immunofluorescence microscopy and demonstrates that the distribution of the HCA on the surface of adjacent stereocilia correlates closely with that of the shaft connectors; i.e., immunostaining is observed up to the tips of the extrastriolar hair cell bundles, but is restricted to the lower regions of hair cell bundles in the striolar region and basilar papilla.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Distribution of the 275 kD hair cell antigen and cell surface specialisations on auditory and vestibular hair bundles in the chicken inner ear. The 275 kD hair cell antigen (HCA) is a protein that is specifically associated with the apical surface of sensory hair cells in the chick inner ear. A comparative study of the vestibular and auditory organs of the inner ear, using both wholemounts and cryosections double labelled for the HCA and F-actin, reveals that two distinct types of hair cells can be distinguished on the basis of antibody staining in each of the vestibular epithelia. One type of hair cell has the HCA restricted to the base of the stereocilia bundle and is found in the striolae of the maculae and in a large, centrally located region of each ampulla. The other type of hair cell is found in the extrastriolar regions of the maculae and the peripheral regions of the ampullae and has the HCA distributed over the entire surface of the stereocilia bundle. In the basilar papilla, the auditory epithelium of the chick inner ear, the HCA is, as in the striolar regions of the maculae, restricted to the base of the hair bundles. In all sensory epithelia the HCA is also present on the apical, nonstereociliary surface of the hair cells. Ultrastructural examination of the basilar papilla and the striolar and the extrastriolar regions of the lagenar macula after staining with ruthenium red and tannic acid shows that there are four morphologically different types of interstereociliary connectors (oblique tip connectors, horizontal tip connectors, shaft connectors and basal connectors) associated with the hair bundles. Oblique tip connectors and basal connectors are found on hair cells from all regions and have a similar distribution. Horizontal tip connectors are seen only on hair cells in the basilar papilla and the striolar region of the lagenar macula. Shaft connectors extend all the way to the tips of extrastriolar hair cell bundles, but extend only a short way up the bundles of hair cells in the basilar papilla and striolar region of the lagenar macula. Immunogold labelling confirms the results obtained with immunofluorescence microscopy and demonstrates that the distribution of the HCA on the surface of adjacent stereocilia correlates closely with that of the shaft connectors; i.e., immunostaining is observed up to the tips of the extrastriolar hair cell bundles, but is restricted to the lower regions of hair cell bundles in the striolar region and basilar papilla.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281175", "title": "Cytoarchitecture and visual field representation in area 17 of the tammar wallaby (Macropus eugenii).", "content": "Tritiated proline was injected into one eye in the tammar wallaby and transported label was studied in the cortex after transneuronal passage through the lateral geniculate nucleus. The autoradiographic label and cytoarchitecture were used to anatomically demarcate the borders of area 17. Electrophysiological recordings from single units were done to obtain a retinotopic map of area 17. Single units in area 17 were found to have orientation sensitivity comparable to those seen in placental mammals such as cat and monkey. They could also be classified as simple, complex, and hypercomplex cells. Changes in the cortical areal magnification factor with eccentricity were found to match the drop off in retinal ganglion cell density only along the vertical meridian representation. Along the horizontal meridian, the cortical magnification falls off significantly with eccentricity, whereas the ganglion cell density shows only a mild reduction. Thus central vision, especially the binocular segment, is heavily represented at the cost of the periphery.", "contents": "Cytoarchitecture and visual field representation in area 17 of the tammar wallaby (Macropus eugenii). Tritiated proline was injected into one eye in the tammar wallaby and transported label was studied in the cortex after transneuronal passage through the lateral geniculate nucleus. The autoradiographic label and cytoarchitecture were used to anatomically demarcate the borders of area 17. Electrophysiological recordings from single units were done to obtain a retinotopic map of area 17. Single units in area 17 were found to have orientation sensitivity comparable to those seen in placental mammals such as cat and monkey. They could also be classified as simple, complex, and hypercomplex cells. Changes in the cortical areal magnification factor with eccentricity were found to match the drop off in retinal ganglion cell density only along the vertical meridian representation. Along the horizontal meridian, the cortical magnification falls off significantly with eccentricity, whereas the ganglion cell density shows only a mild reduction. Thus central vision, especially the binocular segment, is heavily represented at the cost of the periphery."} {"id": "PMID:1281176", "title": "Butyrylcholinesterase-rich neurons in rat brain demonstrated by a sensitive histochemical method.", "content": "Butyrylcholinesterase (BChE) is a highly active enzyme in brain, but little is known about its physiological functions. One obstacle has been the lack of a sensitive and specific method for determining its cellular localization. We report here on a histochemical technique that has permitted BChE to be detected in neuronal, glial, and vascular structures. The method, which utilizes butyrylthiocholine iodide as the substrate, is a modification of our previously described method for acetylcholinesterase (AChE) histochemistry. BChE-rich neuronal somata stained much more intensely than capillaries or glia. Prominent neuronal groups were located in the anterodorsal, laterodorsal, anteroventral, reuniens, centrolateral, paratenial, and periventricular thalamic nuclei, the laterodorsal tegmental nucleus, the pedunculopontine tegmental nucleus, and the dorsal motor nucleus of vagus. Several other areas of the forebrain and brainstem showed modest numbers of positive cells. No positive cells were detected in the striatum, hippocampus, and most parts of the hypothalamus, which are regions containing numerous AChE-rich neurons. Although the distribution pattern of BChE-rich neurons differed from that of AChE-rich neurons, some neuronal groups contained both esterases. The results suggest that BChE may play a unique role in neuronal function, particularly since many BChE-rich neurons have not been identified as to neurotransmitter type.", "contents": "Butyrylcholinesterase-rich neurons in rat brain demonstrated by a sensitive histochemical method. Butyrylcholinesterase (BChE) is a highly active enzyme in brain, but little is known about its physiological functions. One obstacle has been the lack of a sensitive and specific method for determining its cellular localization. We report here on a histochemical technique that has permitted BChE to be detected in neuronal, glial, and vascular structures. The method, which utilizes butyrylthiocholine iodide as the substrate, is a modification of our previously described method for acetylcholinesterase (AChE) histochemistry. BChE-rich neuronal somata stained much more intensely than capillaries or glia. Prominent neuronal groups were located in the anterodorsal, laterodorsal, anteroventral, reuniens, centrolateral, paratenial, and periventricular thalamic nuclei, the laterodorsal tegmental nucleus, the pedunculopontine tegmental nucleus, and the dorsal motor nucleus of vagus. Several other areas of the forebrain and brainstem showed modest numbers of positive cells. No positive cells were detected in the striatum, hippocampus, and most parts of the hypothalamus, which are regions containing numerous AChE-rich neurons. Although the distribution pattern of BChE-rich neurons differed from that of AChE-rich neurons, some neuronal groups contained both esterases. The results suggest that BChE may play a unique role in neuronal function, particularly since many BChE-rich neurons have not been identified as to neurotransmitter type."} {"id": "PMID:1281177", "title": "Mast cells and eosinophils in the allergic mucosal response to allergen challenge: changes in distribution and signs of activation in relation to symptoms.", "content": "An allergen challenge was performed in 10 asymptomatic patients with strictly seasonal allergic rhinitis. For comparison; seven nonallergic subjects were challenged with allergen, and seven allergic patients were challenged with diluent. Cell samples, obtained with use of a brush technique to recover cells from within the epithelium and nasal lavage to collect cells from the epithelial surface, and symptom scores were taken before challenge and at 2-hour intervals during 12 hours. The cell suspensions were cytocentrifuged onto object slides for light microscopy. Histamine was determined in the cell pellets. In brush samples from the allergic patients challenged with allergen, eosinophils, expressed as a percentage of the total granulocytes, increased from 4.3% +/- 2.7% (mean +/- SEM) to 10.3% +/- 3.8% (p < 0.05) 4 hours after challenge. This level was maintained for up to 12 hours. A similar increase was noted in the lavage specimens 2, 6, and 8 hours after the challenge. In the brush samples the proportion of eosinophils containing two or more cytoplasmic vacuoles, taken as a sign of activation, increased from 20% to 72% (p < 0.05) 8 hours after provocation. In brush samples from the allergic patients challenged with allergen, the numbers of metachromatic cells increased to a maximum of eightfold at 10 hours. In the lavage specimens, no metachromatic cells were observed before provocation, but they progressively increased in number 2 to 12 hours after provocation. Cell pellet histamine content decreased temporarily 2 to 4 hours after challenge (p < 0.05) in brush samples from allergen-challenged allergic patients. The local metachromatic cell density before challenge, as reflected in the brush specimens, correlated with nasal congestion, sneezing, and the degree of eosinophilia.", "contents": "Mast cells and eosinophils in the allergic mucosal response to allergen challenge: changes in distribution and signs of activation in relation to symptoms. An allergen challenge was performed in 10 asymptomatic patients with strictly seasonal allergic rhinitis. For comparison; seven nonallergic subjects were challenged with allergen, and seven allergic patients were challenged with diluent. Cell samples, obtained with use of a brush technique to recover cells from within the epithelium and nasal lavage to collect cells from the epithelial surface, and symptom scores were taken before challenge and at 2-hour intervals during 12 hours. The cell suspensions were cytocentrifuged onto object slides for light microscopy. Histamine was determined in the cell pellets. In brush samples from the allergic patients challenged with allergen, eosinophils, expressed as a percentage of the total granulocytes, increased from 4.3% +/- 2.7% (mean +/- SEM) to 10.3% +/- 3.8% (p < 0.05) 4 hours after challenge. This level was maintained for up to 12 hours. A similar increase was noted in the lavage specimens 2, 6, and 8 hours after the challenge. In the brush samples the proportion of eosinophils containing two or more cytoplasmic vacuoles, taken as a sign of activation, increased from 20% to 72% (p < 0.05) 8 hours after provocation. In brush samples from the allergic patients challenged with allergen, the numbers of metachromatic cells increased to a maximum of eightfold at 10 hours. In the lavage specimens, no metachromatic cells were observed before provocation, but they progressively increased in number 2 to 12 hours after provocation. Cell pellet histamine content decreased temporarily 2 to 4 hours after challenge (p < 0.05) in brush samples from allergen-challenged allergic patients. The local metachromatic cell density before challenge, as reflected in the brush specimens, correlated with nasal congestion, sneezing, and the degree of eosinophilia."} {"id": "PMID:1281178", "title": "Identification of common allergenic structures in hazel pollen and hazelnuts: a possible explanation for sensitivity to hazelnuts in patients allergic to tree pollen.", "content": "It is known that most patients with type I allergy to tree pollens also suffer from intolerance to nuts. To identify allergenic structures common to hazel pollen and hazelnuts, cross-reactivity of patients' IgE was investigated. With use of immunoblotting,.serum IgE from 25 patients displaying type I allergic reactions to tree pollens and intolerance to hazelnuts (group I) bound to the 17 kd major hazel pollen allergen Cor a I (100%) and to the 14 kd hazel pollen profilin (16%). IgE binding to proteins of comparable molecular weights in hazelnut extracts was found (18 kd and 14 kd), suggesting that proteins similar to Cor a I and hazel profilin might be also expressed in hazelnuts. In contrast, only four sera (22%) from 18 patients (group II) with tree pollen allergy but without any case history of nut hypersensitivity showed IgE binding to the 18 kd protein of hazelnut extract, and none of these sera exhibited IgE reactivity to the hazelnut profilin. To characterize the hazel pollen and hazelnut allergens, purified recombinant Bet v I (major birch pollen allergen) and purified recombinant Bet v II (birch profilin), respectively, were used for IgE-inhibition experiments. Binding of IgE from patients (with nut allergy) to the blotted hazelnut allergens could be blocked by preincubation of patients' sera with the recombinant proteins. Furthermore, the 18 kd protein of hazelnut extract was purified and induced specific release of histamine from basophils of a patient suffering nut hypersensitivity but not from a healthy control donor. A rabbit antibody raised against celery profilin identified the 14 kd proteins in hazel pollen and hazelnuts as profilin. Our experiments suggest a protein with IgE binding properties similar to the major allergens from pollens of hazel, Cor a I, and of birch, Bet v I, as predominant allergens in hazelnuts, and show that the plant pan-allergen profilin can be detected in both hazel pollen and hazelnut extracts.", "contents": "Identification of common allergenic structures in hazel pollen and hazelnuts: a possible explanation for sensitivity to hazelnuts in patients allergic to tree pollen. It is known that most patients with type I allergy to tree pollens also suffer from intolerance to nuts. To identify allergenic structures common to hazel pollen and hazelnuts, cross-reactivity of patients' IgE was investigated. With use of immunoblotting,.serum IgE from 25 patients displaying type I allergic reactions to tree pollens and intolerance to hazelnuts (group I) bound to the 17 kd major hazel pollen allergen Cor a I (100%) and to the 14 kd hazel pollen profilin (16%). IgE binding to proteins of comparable molecular weights in hazelnut extracts was found (18 kd and 14 kd), suggesting that proteins similar to Cor a I and hazel profilin might be also expressed in hazelnuts. In contrast, only four sera (22%) from 18 patients (group II) with tree pollen allergy but without any case history of nut hypersensitivity showed IgE binding to the 18 kd protein of hazelnut extract, and none of these sera exhibited IgE reactivity to the hazelnut profilin. To characterize the hazel pollen and hazelnut allergens, purified recombinant Bet v I (major birch pollen allergen) and purified recombinant Bet v II (birch profilin), respectively, were used for IgE-inhibition experiments. Binding of IgE from patients (with nut allergy) to the blotted hazelnut allergens could be blocked by preincubation of patients' sera with the recombinant proteins. Furthermore, the 18 kd protein of hazelnut extract was purified and induced specific release of histamine from basophils of a patient suffering nut hypersensitivity but not from a healthy control donor. A rabbit antibody raised against celery profilin identified the 14 kd proteins in hazel pollen and hazelnuts as profilin. Our experiments suggest a protein with IgE binding properties similar to the major allergens from pollens of hazel, Cor a I, and of birch, Bet v I, as predominant allergens in hazelnuts, and show that the plant pan-allergen profilin can be detected in both hazel pollen and hazelnut extracts."} {"id": "PMID:1281179", "title": "Localization of inhaled trimellitic anhydride to lung with a respiratory lymph node antibody secreting cell response.", "content": "Male Sprague-Dawley rats were exposed to trimellitic anhydride (TMA) by inhalation (500 micrograms/m3), 4 hours a day, for 1 to 10 days. TMA was localized to lung cells by immunoelectron microscopy. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used in an attempt to localize TMA to lung lavage proteins. The lung-associated lymph node (LALN) B-lymphocyte response was measured by quantitation of immunoglobulin (Ig)G, IgA, and IgM antibody secreting cells specific for TMA rat serum albumin (TM-RSA) by use of the enzyme-linked immunospot assay (ELISPOT) method. The IgG, IgM, and IgA antibody response to TM-RSA in serum and lavage fluid was quantitated by ELISA. Lung injury was assessed by the number of external lung hemorrhagic foci and lung weight. Immunoelectron microscopy localized TMA to alveolar and bronchial cells on all exposure days. ELISA detected trace amounts of TMA haptenized lavage proteins that could not be detected by Western blot analysis. A marked increase occurred in lung injury from day 7 to 10. The LALN IgG, IgA, and IgM antibody secreting cell response to TM-RSA paralleled measures of lung injury. IgG, IgM, and IgA serum and lavage antibody to TM-RSA were correlated with lung injury measures. Lavage and serum IgG antibody levels had the highest correlation with lung injury.", "contents": "Localization of inhaled trimellitic anhydride to lung with a respiratory lymph node antibody secreting cell response. Male Sprague-Dawley rats were exposed to trimellitic anhydride (TMA) by inhalation (500 micrograms/m3), 4 hours a day, for 1 to 10 days. TMA was localized to lung cells by immunoelectron microscopy. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were used in an attempt to localize TMA to lung lavage proteins. The lung-associated lymph node (LALN) B-lymphocyte response was measured by quantitation of immunoglobulin (Ig)G, IgA, and IgM antibody secreting cells specific for TMA rat serum albumin (TM-RSA) by use of the enzyme-linked immunospot assay (ELISPOT) method. The IgG, IgM, and IgA antibody response to TM-RSA in serum and lavage fluid was quantitated by ELISA. Lung injury was assessed by the number of external lung hemorrhagic foci and lung weight. Immunoelectron microscopy localized TMA to alveolar and bronchial cells on all exposure days. ELISA detected trace amounts of TMA haptenized lavage proteins that could not be detected by Western blot analysis. A marked increase occurred in lung injury from day 7 to 10. The LALN IgG, IgA, and IgM antibody secreting cell response to TM-RSA paralleled measures of lung injury. IgG, IgM, and IgA serum and lavage antibody to TM-RSA were correlated with lung injury measures. Lavage and serum IgG antibody levels had the highest correlation with lung injury."} {"id": "PMID:1281180", "title": "Respiratory allergy to Aspergillus-derived enzymes in bakers' asthma.", "content": "Baking and food industry workers are exposed to several powdered Aspergillus-derived enzymes with carbohydrate-cleaving activity that are commonly used to enhance baked products. We describe a retrospective study of sensitization to fungal alpha-amylase and cellulase on bakers. Five bakers in whom respiratory allergy symptoms developed when they were exposed to bread \"improvers\" that contained fungal alpha-amylase and cellulase were investigated by in vivo and in vitro tests. Type I hypersensitivity to these enzymes was demonstrated in the five patients by means of skin testing, histamine release test, positive reverse enzyme-immunoassay for specific IgE antibodies, and bronchial provocation test response to alpha-amylase or cellulase or both. Isolated immediate and dual responses to the bronchial challenge tests with these enzymes were observed. Immunoblot analysis with use of a pooled serum identified IgE-binding components in both enzymes. In the reverse-enzyme immunoassay-inhibition assays cross-reactivity between alpha-amylase and cellulase was not found, but some degree of cross-reactivity between alpha-amylase and A. oryzae, and between cellulase and A. niger was demonstrated. Four of the patients were also sensitized to cereal flour. Aspergillus-derived enzymes used as flour additives can elicit IgE-mediated respiratory allergy, and this fact has to be considered in the diagnosis and clinical management of bakers' asthma.", "contents": "Respiratory allergy to Aspergillus-derived enzymes in bakers' asthma. Baking and food industry workers are exposed to several powdered Aspergillus-derived enzymes with carbohydrate-cleaving activity that are commonly used to enhance baked products. We describe a retrospective study of sensitization to fungal alpha-amylase and cellulase on bakers. Five bakers in whom respiratory allergy symptoms developed when they were exposed to bread \"improvers\" that contained fungal alpha-amylase and cellulase were investigated by in vivo and in vitro tests. Type I hypersensitivity to these enzymes was demonstrated in the five patients by means of skin testing, histamine release test, positive reverse enzyme-immunoassay for specific IgE antibodies, and bronchial provocation test response to alpha-amylase or cellulase or both. Isolated immediate and dual responses to the bronchial challenge tests with these enzymes were observed. Immunoblot analysis with use of a pooled serum identified IgE-binding components in both enzymes. In the reverse-enzyme immunoassay-inhibition assays cross-reactivity between alpha-amylase and cellulase was not found, but some degree of cross-reactivity between alpha-amylase and A. oryzae, and between cellulase and A. niger was demonstrated. Four of the patients were also sensitized to cereal flour. Aspergillus-derived enzymes used as flour additives can elicit IgE-mediated respiratory allergy, and this fact has to be considered in the diagnosis and clinical management of bakers' asthma."} {"id": "PMID:1281181", "title": "Presence of galanin in rat vagal sensory neurons: evidence from immunohistochemistry and in situ hybridization.", "content": "Galanin (GAL), a 29 amino acid peptide originally isolated from the porcine upper small intestine, is widely distributed in the rat central nervous system, including the area postrema (AP) and nucleus of the solitary tract (NTS). Although vagal sensory neurons terminate in the AP/NTS, it is not known whether these neurons contain GAL in the rat. Therefore, we examined the presence and distribution of GAL in the rat nodose ganglia which contain the cell bodies of vagal sensory neurons. We used avidin-biotin-peroxidase immunohistochemistry and in situ hybridization histochemistry with a 35S-labeled oligonucleotide probe. Results with both techniques revealed the presence of GAL-containing cell bodies and fibers in the nodose ganglion. GAL-like immunoreactive cell bodies, mostly between 25 and 40 microns in diameter, were unevenly scattered throughout the nodose ganglia. The distribution and cell diameter range of GAL mRNA-labeled neurons appeared similar to those of GAL-like immunoreactive cells. These findings suggest a role for GAL in the transmission of visceral sensory information by the vagus nerve in rats.", "contents": "Presence of galanin in rat vagal sensory neurons: evidence from immunohistochemistry and in situ hybridization. Galanin (GAL), a 29 amino acid peptide originally isolated from the porcine upper small intestine, is widely distributed in the rat central nervous system, including the area postrema (AP) and nucleus of the solitary tract (NTS). Although vagal sensory neurons terminate in the AP/NTS, it is not known whether these neurons contain GAL in the rat. Therefore, we examined the presence and distribution of GAL in the rat nodose ganglia which contain the cell bodies of vagal sensory neurons. We used avidin-biotin-peroxidase immunohistochemistry and in situ hybridization histochemistry with a 35S-labeled oligonucleotide probe. Results with both techniques revealed the presence of GAL-containing cell bodies and fibers in the nodose ganglion. GAL-like immunoreactive cell bodies, mostly between 25 and 40 microns in diameter, were unevenly scattered throughout the nodose ganglia. The distribution and cell diameter range of GAL mRNA-labeled neurons appeared similar to those of GAL-like immunoreactive cells. These findings suggest a role for GAL in the transmission of visceral sensory information by the vagus nerve in rats."} {"id": "PMID:1281182", "title": "Brain oxygen transport related to levels of fetal haemoglobin in stable preterm infants.", "content": "The relative amount of regional cerebral oxygen transport was compared between different preterm infants by performing measurements of cerebral blood flow velocity, mean arterial blood pressure, whole blood viscosity and haemoglobin content for each individual. In addition the percentage of fetal haemoglobin was determined. On 25 occasions measurements of fetal haemoglobin and cerebral oxygen transport have been performed prior to and following a blood transfusion with adult red blood cells. Comparison of the data for cerebral oxygen transport suggests that the actual amount of cerebral oxygen transport is lowest at fetal haemoglobin levels below 30% and will increase progressively as soon as the percentage of fetal haemoglobin rises about 30%. Thus, at increasing fetal haemoglobin levels, cerebral haemodynamic mechanisms in the human neonate cause elevations of regional cerebral blood flow and oxygen transport. The found increase of cerebral blood flow and oxygen transport at high fetal haemoglobin levels will minimize the impeded dissociation and delivery of oxygen to brain tissues.", "contents": "Brain oxygen transport related to levels of fetal haemoglobin in stable preterm infants. The relative amount of regional cerebral oxygen transport was compared between different preterm infants by performing measurements of cerebral blood flow velocity, mean arterial blood pressure, whole blood viscosity and haemoglobin content for each individual. In addition the percentage of fetal haemoglobin was determined. On 25 occasions measurements of fetal haemoglobin and cerebral oxygen transport have been performed prior to and following a blood transfusion with adult red blood cells. Comparison of the data for cerebral oxygen transport suggests that the actual amount of cerebral oxygen transport is lowest at fetal haemoglobin levels below 30% and will increase progressively as soon as the percentage of fetal haemoglobin rises about 30%. Thus, at increasing fetal haemoglobin levels, cerebral haemodynamic mechanisms in the human neonate cause elevations of regional cerebral blood flow and oxygen transport. The found increase of cerebral blood flow and oxygen transport at high fetal haemoglobin levels will minimize the impeded dissociation and delivery of oxygen to brain tissues."} {"id": "PMID:1281183", "title": "Corticotrophin-releasing factors in the hypothalamus of the developing fetal sheep.", "content": "Corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are secreted from the hypothalamic median eminence to elicit the secretion of ACTH from the pituitary corticotrophs. During fetal development there is progressive maturation of the hypothalamic-pituitary-adrenal axis, manifest as increasing plasma ACTH and cortisol concentrations, which in species such as sheep culminates in the onset of birth. However, the precise nature of the hypothalamic signal controlling fetal pituitary ACTH secretion remains poorly understood. To investigate the ontogeny of this hypothalamic signal, the present study examined immunoreactive and bioactive ACTH-releasing factors in the developing fetal sheep hypothalamus. Immunoreactive CRH and AVP were measured by radioimmunoassay in extracts of hypothalami taken at day 70, day 100, and day 130 gestation (term = 145 days). There was a progressive and significant (P < 0.01) increase in hypothalamic CRH and AVP concentrations which was particularly marked between d100 and d130 gestation. AVP was always present in higher concentrations that CRH, although this difference was significantly reduced by day 130 gestation as the result of a large increase in the content of CRH relative to AVP. Sephadex G50 chromatography revealed that immunoreactive CRH and AVP in hypothalamic extracts existed as single molecular forms corresponding to synthetic peptides at each gestational age. In addition, these immunoreactive forms of CRH and AVP possessed significant ACTH-releasing bioactivity as measured in primary cultures of adult sheep anterior pituitary cells. Furthermore, significant bioactivity was present in high and low molecular weight fractions eluted after chromatography which did not contain any CRH or AVP immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Corticotrophin-releasing factors in the hypothalamus of the developing fetal sheep. Corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) are secreted from the hypothalamic median eminence to elicit the secretion of ACTH from the pituitary corticotrophs. During fetal development there is progressive maturation of the hypothalamic-pituitary-adrenal axis, manifest as increasing plasma ACTH and cortisol concentrations, which in species such as sheep culminates in the onset of birth. However, the precise nature of the hypothalamic signal controlling fetal pituitary ACTH secretion remains poorly understood. To investigate the ontogeny of this hypothalamic signal, the present study examined immunoreactive and bioactive ACTH-releasing factors in the developing fetal sheep hypothalamus. Immunoreactive CRH and AVP were measured by radioimmunoassay in extracts of hypothalami taken at day 70, day 100, and day 130 gestation (term = 145 days). There was a progressive and significant (P < 0.01) increase in hypothalamic CRH and AVP concentrations which was particularly marked between d100 and d130 gestation. AVP was always present in higher concentrations that CRH, although this difference was significantly reduced by day 130 gestation as the result of a large increase in the content of CRH relative to AVP. Sephadex G50 chromatography revealed that immunoreactive CRH and AVP in hypothalamic extracts existed as single molecular forms corresponding to synthetic peptides at each gestational age. In addition, these immunoreactive forms of CRH and AVP possessed significant ACTH-releasing bioactivity as measured in primary cultures of adult sheep anterior pituitary cells. Furthermore, significant bioactivity was present in high and low molecular weight fractions eluted after chromatography which did not contain any CRH or AVP immunoreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281184", "title": "Diagnostic techniques.", "content": "Use of the ocular microbiology techniques described in this article when inoculating specimens greatly reduces, if not eliminates, the confusion that occurs when an organism that is part of the normal flora or that is common in the environment is found in specimens of ocular material. The growth of microorganisms can be quantified. The results of lid and conjunctival cultures can be compared with growth from the cornea or anterior chamber and vitreous fluids to provide clues to the likely significance of the isolate.", "contents": "Diagnostic techniques. Use of the ocular microbiology techniques described in this article when inoculating specimens greatly reduces, if not eliminates, the confusion that occurs when an organism that is part of the normal flora or that is common in the environment is found in specimens of ocular material. The growth of microorganisms can be quantified. The results of lid and conjunctival cultures can be compared with growth from the cornea or anterior chamber and vitreous fluids to provide clues to the likely significance of the isolate."} {"id": "PMID:1281185", "title": "Evidence for voltage modulation of IL-2 production in mitogen-stimulated human peripheral blood lymphocytes.", "content": "The membrane potential of human PBMC was modulated in culture by isotonic high extracellular K+ (K+e), or the K+ channel blocker, charybdotoxin (ChTX), to determine the effect of depolarization on stimulated proliferation, IL-2 elaboration, and gene expression. In serum-free cultures, ChTX and high [K+]e induced a specific dose-dependent decrease in IL-2 production. ChTX inhibited proliferation of PBMC and purified T cells, decreased IL-2 elaboration 15 h after stimulation by 78.4 +/- 5.3% (n = 5), and decreased IL-2 mRNA steady-state levels by 80% between 8 and 10 h after stimulation. The IC50 for ChTX-inhibition of IL-2 elaboration and IL-2 mRNA were both 1 nM. Similarly, high [K+]e inhibited proliferation with an IC50 of 38.9 +/- 1.1 mM (n = 13), decreased IL-2 elaboration with an IC50 of 21.3 +/- 1.2 mM (n = 6), and decreased IL-2 mRNA steady-state levels with an IC50 of 18 mM. The sensitivities of both IL-2 production and proliferation to depolarization were substantially reduced by calcium, serum, and exogenous rIL-2. From these findings we conclude that membrane potential may contribute to the control of immune responsiveness in vivo.", "contents": "Evidence for voltage modulation of IL-2 production in mitogen-stimulated human peripheral blood lymphocytes. The membrane potential of human PBMC was modulated in culture by isotonic high extracellular K+ (K+e), or the K+ channel blocker, charybdotoxin (ChTX), to determine the effect of depolarization on stimulated proliferation, IL-2 elaboration, and gene expression. In serum-free cultures, ChTX and high [K+]e induced a specific dose-dependent decrease in IL-2 production. ChTX inhibited proliferation of PBMC and purified T cells, decreased IL-2 elaboration 15 h after stimulation by 78.4 +/- 5.3% (n = 5), and decreased IL-2 mRNA steady-state levels by 80% between 8 and 10 h after stimulation. The IC50 for ChTX-inhibition of IL-2 elaboration and IL-2 mRNA were both 1 nM. Similarly, high [K+]e inhibited proliferation with an IC50 of 38.9 +/- 1.1 mM (n = 13), decreased IL-2 elaboration with an IC50 of 21.3 +/- 1.2 mM (n = 6), and decreased IL-2 mRNA steady-state levels with an IC50 of 18 mM. The sensitivities of both IL-2 production and proliferation to depolarization were substantially reduced by calcium, serum, and exogenous rIL-2. From these findings we conclude that membrane potential may contribute to the control of immune responsiveness in vivo."} {"id": "PMID:1281186", "title": "CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production.", "content": "Ag-presenting cells provide at least two distinct signals for T cell activation. T cell receptor-dependent stimulation is provided by presentation of a specific peptide Ag in association with MHC molecules. In addition, APC also supply costimulatory signals required for T cell activation that are neither Ag- nor MHC restricted. One such costimulatory signal is mediated via the interaction of B7 on APC with the CD28 receptor on T cells. Recently, CTLA-4 has been shown to be a second B7 receptor on T cells. In the present report, we have examined the expression of CD28 and CTLA-4 on a panel of resting and activated normal T cell subsets and T cell clones by RNA blot analysis in an attempt to determine whether their expression defines reciprocal or overlapping subsets. CD28 was detected in resting T cells, whereas CTLA-4 was not. After stimulation with PHA and PMA for 24 h, CTLA-4 mRNA was expressed in both the CD4+ and CD8+ subsets as well as in CD28+ T cells. We examined 37 human and six murine T cell clones that had been previously characterized for their cytokine production. After activation, CTLA-4 and CD28 mRNA were coexpressed in 36 of 37 human T cell clones and all six murine T cell clones. These included T cells of CD4+8-, CD4-8+, and CD4-8- phenotypes as well as clones with Th1 and Th2 cytokine profiles. In contrast, CD28 but not CTLA-4 mRNA was detected in leukemic T cell lines and myelomas. CTLA-4 and B7 mRNA but not CD28 mRNA was detected in two long term HTLV-I-transformed T cell lines. These data demonstrate that CD28 and CTLA-4 mRNA are coexpressed in most activated T cells and T cell clones, providing evidence that they do not define reciprocal subsets. Moreover, they are consistent with the hypothesis that B7 transmits its signal through a single receptor, CD28, on resting T cells, and multiple receptors, CD28 and CTLA-4, on activated T cells.", "contents": "CTLA-4 and CD28 mRNA are coexpressed in most T cells after activation. Expression of CTLA-4 and CD28 mRNA does not correlate with the pattern of lymphokine production. Ag-presenting cells provide at least two distinct signals for T cell activation. T cell receptor-dependent stimulation is provided by presentation of a specific peptide Ag in association with MHC molecules. In addition, APC also supply costimulatory signals required for T cell activation that are neither Ag- nor MHC restricted. One such costimulatory signal is mediated via the interaction of B7 on APC with the CD28 receptor on T cells. Recently, CTLA-4 has been shown to be a second B7 receptor on T cells. In the present report, we have examined the expression of CD28 and CTLA-4 on a panel of resting and activated normal T cell subsets and T cell clones by RNA blot analysis in an attempt to determine whether their expression defines reciprocal or overlapping subsets. CD28 was detected in resting T cells, whereas CTLA-4 was not. After stimulation with PHA and PMA for 24 h, CTLA-4 mRNA was expressed in both the CD4+ and CD8+ subsets as well as in CD28+ T cells. We examined 37 human and six murine T cell clones that had been previously characterized for their cytokine production. After activation, CTLA-4 and CD28 mRNA were coexpressed in 36 of 37 human T cell clones and all six murine T cell clones. These included T cells of CD4+8-, CD4-8+, and CD4-8- phenotypes as well as clones with Th1 and Th2 cytokine profiles. In contrast, CD28 but not CTLA-4 mRNA was detected in leukemic T cell lines and myelomas. CTLA-4 and B7 mRNA but not CD28 mRNA was detected in two long term HTLV-I-transformed T cell lines. These data demonstrate that CD28 and CTLA-4 mRNA are coexpressed in most activated T cells and T cell clones, providing evidence that they do not define reciprocal subsets. Moreover, they are consistent with the hypothesis that B7 transmits its signal through a single receptor, CD28, on resting T cells, and multiple receptors, CD28 and CTLA-4, on activated T cells."} {"id": "PMID:1281187", "title": "Murine B7 antigen provides a sufficient costimulatory signal for antigen-specific and MHC-restricted T cell activation.", "content": "We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-Ad molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-Ad/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-Ad molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation.", "contents": "Murine B7 antigen provides a sufficient costimulatory signal for antigen-specific and MHC-restricted T cell activation. We have previously shown that the murine B7 (mB7) molecule, when expressed in Chinese hamster ovary cells in stable fashion, can costimulate with anti-CD3 mAb or Con A to induce T cell activation. We have now derived, by gene transfection, Chinese hamster ovary cell lines that express the I-Ad molecule, either alone or in context with mB7. We have analyzed these transfectants for their capacity to present Ag to murine CD4+ T lymphocytes. I-Ad/mB7-double transfectants were able to stimulate mixed lymphocyte reactions and to present peptide Ag to specific T cells. Chinese hamster ovary cells that expressed only the I-Ad molecule were not able to stimulate T cell proliferation in these systems. Thus, the mB7 protein is a sufficient costimulatory molecule for the physiologic, Ag-dependent/MHC-restricted activation of murine CD4+ T cells. Stimulation of T cell bulk cultures resulted predominantly in the production of IL-2 and not of IL-4. The costimulatory activity of mB7 is not, however, restricted to the IL-2-secreting subset. We have identified one IL-4-secreting T cell clone, CDC35, which is responsive to mB7 triggering. Finally, we present experiments that suggest that mB7 and peptide/MHC complexes need to be expressed on the same cell for optimal induction of T cell activation."} {"id": "PMID:1281188", "title": "Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation.", "content": "Treatment of T cells with the cysteine protease bromelain has been widely used to enhance the binding of human T cells to human E (autologous E rosettes) and has been shown to remove surface T cell CD44 molecules. Ligand binding to CD44 has been shown to markedly augment T cell activation. To study the activation potential of bromelain-treated CD44 T cells, we have compared the proliferation of sham- and bromelain-treated normal human PBMC to mitogenic CD2 mAb. We found that bromelain not only removed T cell CD44, but also removed the CD45RA isoform of CD45 as well as E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 molecules. T cell proliferation in response to CD2 mAb was increased 325% in bromelain-treated PBMC compared to sham-treated PBMC (p < 0.005). Reciprocal treatment experiments using purified T cells and monocytes demonstrated that the enhancement of T cell CD2 activation by bromelain occurred only when T cells were treated with bromelain and was accompanied by increased adhesion of T cells to monocytes. These data demonstrate that expression of portions of the extracellular domains of the CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules are not required for CD2 activation of human T cells. Rather, the removal of these surface molecules by bromelain is associated with enhanced T cell-monocyte aggregation and enhanced CD2-mediated T cell activation. Taken together with data that CD44, E2/MIC2, CD6, and CD7 mAb inhibit CD2/lymphocyte function-associated Ag-3-mediated cellular interactions and also augment CD2-mediated triggering of T cells, these data suggest that members of the bromelain-sensitive group of surface molecules may comprise a set of CD2-associated adhesion ligands that acts in concert to modulate human T cell activation.", "contents": "Bromelain treatment of human T cells removes CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules and markedly enhances CD2-mediated T cell activation. Treatment of T cells with the cysteine protease bromelain has been widely used to enhance the binding of human T cells to human E (autologous E rosettes) and has been shown to remove surface T cell CD44 molecules. Ligand binding to CD44 has been shown to markedly augment T cell activation. To study the activation potential of bromelain-treated CD44 T cells, we have compared the proliferation of sham- and bromelain-treated normal human PBMC to mitogenic CD2 mAb. We found that bromelain not only removed T cell CD44, but also removed the CD45RA isoform of CD45 as well as E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 molecules. T cell proliferation in response to CD2 mAb was increased 325% in bromelain-treated PBMC compared to sham-treated PBMC (p < 0.005). Reciprocal treatment experiments using purified T cells and monocytes demonstrated that the enhancement of T cell CD2 activation by bromelain occurred only when T cells were treated with bromelain and was accompanied by increased adhesion of T cells to monocytes. These data demonstrate that expression of portions of the extracellular domains of the CD44, CD45RA, E2/MIC2, CD6, CD7, CD8, and Leu 8/LAM1 surface molecules are not required for CD2 activation of human T cells. Rather, the removal of these surface molecules by bromelain is associated with enhanced T cell-monocyte aggregation and enhanced CD2-mediated T cell activation. Taken together with data that CD44, E2/MIC2, CD6, and CD7 mAb inhibit CD2/lymphocyte function-associated Ag-3-mediated cellular interactions and also augment CD2-mediated triggering of T cells, these data suggest that members of the bromelain-sensitive group of surface molecules may comprise a set of CD2-associated adhesion ligands that acts in concert to modulate human T cell activation."} {"id": "PMID:1281189", "title": "Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help.", "content": "In lymphoid follicles, CD4+ T lymphocytes provide contact-dependent stimuli to B cells that are critical for the generation of specific antibody responses in a process termed Th function. The CD4+ T cell-restricted surface activation protein, 5c8 Ag (T-BAM), has recently been shown to be a component of the contact-dependent helper signal to B cells. To further dissect this process, we utilized a Jurkat T cell lymphoma clone, termed D1.1, that constitutively expresses T-BAM and activates peripheral B cells to express surface CD23 in a contact-dependent mechanism that is inhibited by mAb anti-T-BAM (5c8). Similar to its effect on peripheral B cells, Jurkat D1.1 activates B cells from lymphoid organs, as well as a B cell lymphoma clone, RAMOS 266,4CN 3F10 (RAMOS 266), to up-regulate surface CD23. Interestingly, mAb to the B cell surface molecule, CD40 (mAb G28-5 and B-B20), inhibit D1.1 induced activation of RAMOS 266 and peripheral and lymphoid B cells. In contrast, mAb to CR2 or the adhesion molecules, LFA1, LFA3, or ICAM-1, have little effect. The inhibitory effect of anti-CD40 mAb on B cell activation induced by D1.1 is specific because anti-CD40 potentiates, rather than inhibits, the up-regulation of CD23 on B cells induced by rIL-4. Moreover, cross-linking CD40 molecules by anti-CD40 mAb bound to Fc gamma RII+ (CD32) L cells induces B cell CD23 expression. In vivo, T-BAM-expressing cells are CD4+ T cells that are restricted to lymphoid organs and are localized in the mantle and centrocytic zones of lymphoid follicles and the spleen periarteriolar lymphoid sheath in association with CD40+ B cells. Taken together, these data demonstrate that T-BAM on T cells and CD40 on B cells are involved in contact-dependent T-B help interactions that occur in lymphoid follicles.", "contents": "Molecular interactions mediating T-B lymphocyte collaboration in human lymphoid follicles. Roles of T cell-B-cell-activating molecule (5c8 antigen) and CD40 in contact-dependent help. In lymphoid follicles, CD4+ T lymphocytes provide contact-dependent stimuli to B cells that are critical for the generation of specific antibody responses in a process termed Th function. The CD4+ T cell-restricted surface activation protein, 5c8 Ag (T-BAM), has recently been shown to be a component of the contact-dependent helper signal to B cells. To further dissect this process, we utilized a Jurkat T cell lymphoma clone, termed D1.1, that constitutively expresses T-BAM and activates peripheral B cells to express surface CD23 in a contact-dependent mechanism that is inhibited by mAb anti-T-BAM (5c8). Similar to its effect on peripheral B cells, Jurkat D1.1 activates B cells from lymphoid organs, as well as a B cell lymphoma clone, RAMOS 266,4CN 3F10 (RAMOS 266), to up-regulate surface CD23. Interestingly, mAb to the B cell surface molecule, CD40 (mAb G28-5 and B-B20), inhibit D1.1 induced activation of RAMOS 266 and peripheral and lymphoid B cells. In contrast, mAb to CR2 or the adhesion molecules, LFA1, LFA3, or ICAM-1, have little effect. The inhibitory effect of anti-CD40 mAb on B cell activation induced by D1.1 is specific because anti-CD40 potentiates, rather than inhibits, the up-regulation of CD23 on B cells induced by rIL-4. Moreover, cross-linking CD40 molecules by anti-CD40 mAb bound to Fc gamma RII+ (CD32) L cells induces B cell CD23 expression. In vivo, T-BAM-expressing cells are CD4+ T cells that are restricted to lymphoid organs and are localized in the mantle and centrocytic zones of lymphoid follicles and the spleen periarteriolar lymphoid sheath in association with CD40+ B cells. Taken together, these data demonstrate that T-BAM on T cells and CD40 on B cells are involved in contact-dependent T-B help interactions that occur in lymphoid follicles."} {"id": "PMID:1281190", "title": "Role of antigen-specific T cell help in the generation of in vivo antibody responses. I. Antigen-specific T cell help is required to generate a polyclonal IgG1 response in anti-IgD antibody-injected mice.", "content": "A system in which injection of mice with an antibody to mouse IgD that they recognize as foreign stimulates a large, T cell-dependent IgG response was used to study whether Ag-specific T cell help is required to stimulate polyclonal (non-Ag-specific) IgG production in vivo. Igha x Ighb allotype heterozygous mice were injected with a conjugate of a foreign Ag coupled to a mAb specific for one of the two IgD allotypes expressed in these mice. This conjugate cross-links mIgD on B cells that express the recognized allotype. These cells process the conjugate and present the foreign Ag to Ag-specific T lymphocytes, which become activated. Thus, B cells of the recognized allotype can be stimulated by cross-linking of their mIgD, Ag-specific T cell help, non-Ag-specific cytokines, and non-Ag-specific contact with activated T cells. In contrast, B cells that express the Igh allotype not recognized by the Ag-anti-IgD antibody conjugate (bystander B cells) can be stimulated in this system only by non-Ag-specific cytokines and non-Ag-specific contact with activated T cells. Although both recognized and bystander B cells in conjugate-injected mice demonstrated substantial increases in size and Ia expression, only the recognized B cells were induced to synthesize DNA and to make a substantial polyclonal Ig response. Bystander B cells still failed to secrete IgG when mice were injected with an anti-IgD-Ag conjugate specific for the other Igh allotype as well as a mAb that cross-linked IgD of the bystander B cell allotype. These observations demonstrate that although non-Ag-specific cytokine and contact-mediated T cell help are sufficient to induce B cells to increase in size and Ia expression in anti-IgD antibody-injected mice, Ag-specific T cell help is required to stimulate the generation of an IgG response in these mice.", "contents": "Role of antigen-specific T cell help in the generation of in vivo antibody responses. I. Antigen-specific T cell help is required to generate a polyclonal IgG1 response in anti-IgD antibody-injected mice. A system in which injection of mice with an antibody to mouse IgD that they recognize as foreign stimulates a large, T cell-dependent IgG response was used to study whether Ag-specific T cell help is required to stimulate polyclonal (non-Ag-specific) IgG production in vivo. Igha x Ighb allotype heterozygous mice were injected with a conjugate of a foreign Ag coupled to a mAb specific for one of the two IgD allotypes expressed in these mice. This conjugate cross-links mIgD on B cells that express the recognized allotype. These cells process the conjugate and present the foreign Ag to Ag-specific T lymphocytes, which become activated. Thus, B cells of the recognized allotype can be stimulated by cross-linking of their mIgD, Ag-specific T cell help, non-Ag-specific cytokines, and non-Ag-specific contact with activated T cells. In contrast, B cells that express the Igh allotype not recognized by the Ag-anti-IgD antibody conjugate (bystander B cells) can be stimulated in this system only by non-Ag-specific cytokines and non-Ag-specific contact with activated T cells. Although both recognized and bystander B cells in conjugate-injected mice demonstrated substantial increases in size and Ia expression, only the recognized B cells were induced to synthesize DNA and to make a substantial polyclonal Ig response. Bystander B cells still failed to secrete IgG when mice were injected with an anti-IgD-Ag conjugate specific for the other Igh allotype as well as a mAb that cross-linked IgD of the bystander B cell allotype. These observations demonstrate that although non-Ag-specific cytokine and contact-mediated T cell help are sufficient to induce B cells to increase in size and Ia expression in anti-IgD antibody-injected mice, Ag-specific T cell help is required to stimulate the generation of an IgG response in these mice."} {"id": "PMID:1281191", "title": "Role of antigen-specific T cell help in the generation of in vivo antibody responses. II. Sustained antigen-specific T cell help is required to induce a specific antibody response.", "content": "The injection of mice with a goat or rabbit antibody to mouse IgD stimulates a large polyclonal IgG response, approximately 10% of which is specific for antigenic determinants on the anti-IgD antibody molecule. The large goat IgG (GIgG)-specific antibody response in mice injected with goat antibody to mouse IgD requires that GIgG-specific B cells undergo much greater clonal expansion than B cells specific for other Ag. One possible explanation for the greater clonal expansion of GIgG-specific B cells is that B cells that lack GIgG specificity can only be stimulated with GIgG-specific T help during the relatively short time that anti-IgD binds to, and is processed and presented by, these B cells before they cease to express membrane mIgD. In contrast, GIgG-specific B cells can continue to bind, process, and present GIgG through mIgM after they lose mIgD. To test the hypothesis that extended stimulation with Ag-specific T help is required to generate a specific antibody response, we determined time requirements for Ag-specific T cell help for the development of such a response. Mice were injected with rabbit antibody to mouse IgD plus one or more daily injections of FITC conjugated to a F(ab')2 fragment of rabbit IgG (FITC-(Fab')2), which has a short in vivo half-life, and IgG1 anti-FITC antibody production was analyzed. In this system, each additional injection of FITC-F(ab')2 extends the period during which FITC-specific B cells can process this Ag and present it to rabbit IgG-specific T cells. Each additional injection of FITC-F(ab')2 stimulated a several-fold increase in IgG1 anti-FITC antibody levels, and injections on 5 consecutive days were required to induce a maximal anti-FITC response. These observations provide evidence that sustained Ag-specific T cell help is required to stimulate the degree of B cell clonal expansion that characterizes a specific antibody response.", "contents": "Role of antigen-specific T cell help in the generation of in vivo antibody responses. II. Sustained antigen-specific T cell help is required to induce a specific antibody response. The injection of mice with a goat or rabbit antibody to mouse IgD stimulates a large polyclonal IgG response, approximately 10% of which is specific for antigenic determinants on the anti-IgD antibody molecule. The large goat IgG (GIgG)-specific antibody response in mice injected with goat antibody to mouse IgD requires that GIgG-specific B cells undergo much greater clonal expansion than B cells specific for other Ag. One possible explanation for the greater clonal expansion of GIgG-specific B cells is that B cells that lack GIgG specificity can only be stimulated with GIgG-specific T help during the relatively short time that anti-IgD binds to, and is processed and presented by, these B cells before they cease to express membrane mIgD. In contrast, GIgG-specific B cells can continue to bind, process, and present GIgG through mIgM after they lose mIgD. To test the hypothesis that extended stimulation with Ag-specific T help is required to generate a specific antibody response, we determined time requirements for Ag-specific T cell help for the development of such a response. Mice were injected with rabbit antibody to mouse IgD plus one or more daily injections of FITC conjugated to a F(ab')2 fragment of rabbit IgG (FITC-(Fab')2), which has a short in vivo half-life, and IgG1 anti-FITC antibody production was analyzed. In this system, each additional injection of FITC-F(ab')2 extends the period during which FITC-specific B cells can process this Ag and present it to rabbit IgG-specific T cells. Each additional injection of FITC-F(ab')2 stimulated a several-fold increase in IgG1 anti-FITC antibody levels, and injections on 5 consecutive days were required to induce a maximal anti-FITC response. These observations provide evidence that sustained Ag-specific T cell help is required to stimulate the degree of B cell clonal expansion that characterizes a specific antibody response."} {"id": "PMID:1281192", "title": "CD5+ B cells predominate in peripheral tissues of rabbit.", "content": "Restricted usage of VH genes is observed in rabbit B lymphocytes and in human and murine CD5 B lymphocytes. This observation raised the possibility that most rabbit B lymphocytes were CD5+. To investigate this we cloned the CD5 gene from a rabbit cosmid library, using a probe derived from human CD5 cDNA. The rabbit CD5 gene was transfected into a murine T cell line and then we used the transfectants to develop anti-rabbit CD5 mAb. By Western blot analysis, the mAb reacted with a 67-kDa protein in lysates prepared from mesenteric lymph node and spleen cells. We determined the frequency of CD5+ B lymphocytes in peripheral lymphoid tissues of adult rabbits by two-color immunofluorescence analysis using anti-CD5 mAb and anti-L chain antibodies. The analysis showed that essentially all peripheral B lymphocytes in adult rabbits express CD5. The observation that CD5 is expressed on nearly all rabbit B lymphocytes contrasts markedly to mouse and human, where only a small number of B lymphocytes express CD5. We propose that most peripheral B lymphocytes in rabbit, as in chicken, develop early in ontogeny and are maintained throughout life by a self-renewing process.", "contents": "CD5+ B cells predominate in peripheral tissues of rabbit. Restricted usage of VH genes is observed in rabbit B lymphocytes and in human and murine CD5 B lymphocytes. This observation raised the possibility that most rabbit B lymphocytes were CD5+. To investigate this we cloned the CD5 gene from a rabbit cosmid library, using a probe derived from human CD5 cDNA. The rabbit CD5 gene was transfected into a murine T cell line and then we used the transfectants to develop anti-rabbit CD5 mAb. By Western blot analysis, the mAb reacted with a 67-kDa protein in lysates prepared from mesenteric lymph node and spleen cells. We determined the frequency of CD5+ B lymphocytes in peripheral lymphoid tissues of adult rabbits by two-color immunofluorescence analysis using anti-CD5 mAb and anti-L chain antibodies. The analysis showed that essentially all peripheral B lymphocytes in adult rabbits express CD5. The observation that CD5 is expressed on nearly all rabbit B lymphocytes contrasts markedly to mouse and human, where only a small number of B lymphocytes express CD5. We propose that most peripheral B lymphocytes in rabbit, as in chicken, develop early in ontogeny and are maintained throughout life by a self-renewing process."} {"id": "PMID:1281193", "title": "Expression of surface lymphotoxin and tumor necrosis factor on activated T, B, and natural killer cells.", "content": "The expression of membrane-associated forms of lymphotoxin (LT) and TNF were examined on cell lines of T, B, and myeloid origin, IL-2 dependent T cell clones, and peripheral blood lymphocytes. Inducible and constitutive patterns of surface LT expression were found on T cells as exemplified by the II-23.D7, a CD4+T cell hybridoma, and HUT-78, a T cell lymphoma. Phorbol ester induced surface LT expression on Ramos, an EBV transformed B cell line, but at a slower rate of appearance when compared to the II-23.D7. Secretion of LT was rapidly inducible by phorbol ester in II-23.D7 and also in HUT-78 but with slower kinetics; surface LT expression continued in both lines after secretion had ceased. Low levels of membrane TNF were transiently induced on II-23.D7 and HUT-78, but none was observed on Ramos. Peripheral blood monocytes and some myeloid tumor lines did not express surface LT. Several T cell clones expressed surface LT after Ag-specific stimulation, and expression persisted several days. Stimulation through the TCR or by IL-2 rapidly induced surface LT on resting peripheral T cells and CD56+ NK cells; pokeweed mitogen activation induced expression on CD20+ B cells. Consistent with previous results, immunoprecipitation with anti-LT mAb showed that LT was complexed with a distinct 33 kDa glycoprotein (p33) on cells that expressed surface LT, whereas secreted LT was not associated with p33. Surface and secreted modes of LT expression by activated T, B, and NK cells suggests that LT can be utilized as either a localized or diffusible mediator in immune responses.", "contents": "Expression of surface lymphotoxin and tumor necrosis factor on activated T, B, and natural killer cells. The expression of membrane-associated forms of lymphotoxin (LT) and TNF were examined on cell lines of T, B, and myeloid origin, IL-2 dependent T cell clones, and peripheral blood lymphocytes. Inducible and constitutive patterns of surface LT expression were found on T cells as exemplified by the II-23.D7, a CD4+T cell hybridoma, and HUT-78, a T cell lymphoma. Phorbol ester induced surface LT expression on Ramos, an EBV transformed B cell line, but at a slower rate of appearance when compared to the II-23.D7. Secretion of LT was rapidly inducible by phorbol ester in II-23.D7 and also in HUT-78 but with slower kinetics; surface LT expression continued in both lines after secretion had ceased. Low levels of membrane TNF were transiently induced on II-23.D7 and HUT-78, but none was observed on Ramos. Peripheral blood monocytes and some myeloid tumor lines did not express surface LT. Several T cell clones expressed surface LT after Ag-specific stimulation, and expression persisted several days. Stimulation through the TCR or by IL-2 rapidly induced surface LT on resting peripheral T cells and CD56+ NK cells; pokeweed mitogen activation induced expression on CD20+ B cells. Consistent with previous results, immunoprecipitation with anti-LT mAb showed that LT was complexed with a distinct 33 kDa glycoprotein (p33) on cells that expressed surface LT, whereas secreted LT was not associated with p33. Surface and secreted modes of LT expression by activated T, B, and NK cells suggests that LT can be utilized as either a localized or diffusible mediator in immune responses."} {"id": "PMID:1281194", "title": "Genomic structure and chromosomal mapping of the murine CD40 gene.", "content": "The B cell-associated surface molecule, CD40, is likely to play a central role in the expansion of Ag-stimulated B cells, and their interaction with activated Th cells. In our study we have isolated genomic clones of murine CD40 from a mouse liver genomic DNA library. Comparison with the murine CD40 cDNA sequence revealed the presence of nine exons that together contain the entire murine CD40 coding region, and span approximately 16.3 kb of genomic DNA. The intron/exon structure of the CD40 gene resembles that of the low affinity nerve growth factor receptor gene, a close homolog of both human and murine CD40. In both cases the functional domains of the receptor molecules are separated onto different exons throughout the genes. Southern blot analysis demonstrated that murine CD40 is a single copy gene that maps in the distal region of mouse chromosome 2.", "contents": "Genomic structure and chromosomal mapping of the murine CD40 gene. The B cell-associated surface molecule, CD40, is likely to play a central role in the expansion of Ag-stimulated B cells, and their interaction with activated Th cells. In our study we have isolated genomic clones of murine CD40 from a mouse liver genomic DNA library. Comparison with the murine CD40 cDNA sequence revealed the presence of nine exons that together contain the entire murine CD40 coding region, and span approximately 16.3 kb of genomic DNA. The intron/exon structure of the CD40 gene resembles that of the low affinity nerve growth factor receptor gene, a close homolog of both human and murine CD40. In both cases the functional domains of the receptor molecules are separated onto different exons throughout the genes. Southern blot analysis demonstrated that murine CD40 is a single copy gene that maps in the distal region of mouse chromosome 2."} {"id": "PMID:1281195", "title": "Deletion mapping of Ig VH gene segments expressed in human CD5 B cell lines. JH proximity is not the sole determinant of the restricted fetal VH gene repertoire.", "content": "VH gene segments expressed in a panel of monoclonal human CD5 B cell lines have been positioned on the IgH locus by deletion mapping. The analysis yielded a relative order of VH fragments of the VH2, VH4, VH5, and VH6 gene families that was consistent with, and provided a further refinement of existing maps of the human IgH locus. We demonstrate that four of six VH gene segments expressed in the CD5 B cell lines map > 500 kb from the cluster of JH segments. Two of the gene segments, positioned at approximately 850 kb (58p2) and approximately 500 kb (1-9III) from the JH segments, respectively, belong to the previously identified small cohort of second trimester fetal VH gene segments. The data show that JH proximity is not the sole determinant of restricted VH gene utilization in early human ontogeny.", "contents": "Deletion mapping of Ig VH gene segments expressed in human CD5 B cell lines. JH proximity is not the sole determinant of the restricted fetal VH gene repertoire. VH gene segments expressed in a panel of monoclonal human CD5 B cell lines have been positioned on the IgH locus by deletion mapping. The analysis yielded a relative order of VH fragments of the VH2, VH4, VH5, and VH6 gene families that was consistent with, and provided a further refinement of existing maps of the human IgH locus. We demonstrate that four of six VH gene segments expressed in the CD5 B cell lines map > 500 kb from the cluster of JH segments. Two of the gene segments, positioned at approximately 850 kb (58p2) and approximately 500 kb (1-9III) from the JH segments, respectively, belong to the previously identified small cohort of second trimester fetal VH gene segments. The data show that JH proximity is not the sole determinant of restricted VH gene utilization in early human ontogeny."} {"id": "PMID:1281196", "title": "Highly diverse T cell recognition of a single Plasmodium berghei peptide presented by a series of mutant H-2Kd molecules.", "content": "We have tested 21 independent CTL clones for recognition of a single peptide derived from the Plasmodium berghei circumsporozoite protein in the context of 13 mutants of the murine MHC class I molecule H-2Kd. In this series of Kd mutants, amino acid residues located on the upper surface of the alpha-helices were individually substituted by alanine. Remarkably, most clones displayed individual recognition patterns on the Kd mutants. We had previously found that this series of CTL clones was likewise highly diverse in terms of both TCR primary structure and peptide fine specificity. Our data thus reinforce the concept that multiple T cell epitopes are available on the surface of a single peptide-MHC class I complex for recognition by specific TCR.", "contents": "Highly diverse T cell recognition of a single Plasmodium berghei peptide presented by a series of mutant H-2Kd molecules. We have tested 21 independent CTL clones for recognition of a single peptide derived from the Plasmodium berghei circumsporozoite protein in the context of 13 mutants of the murine MHC class I molecule H-2Kd. In this series of Kd mutants, amino acid residues located on the upper surface of the alpha-helices were individually substituted by alanine. Remarkably, most clones displayed individual recognition patterns on the Kd mutants. We had previously found that this series of CTL clones was likewise highly diverse in terms of both TCR primary structure and peptide fine specificity. Our data thus reinforce the concept that multiple T cell epitopes are available on the surface of a single peptide-MHC class I complex for recognition by specific TCR."} {"id": "PMID:1281197", "title": "T and B cell epitope mapping of SM23, an integral membrane protein of Schistosoma mansoni.", "content": "SM23 is an integral membrane protein of the blood-vessel dwelling parasitic worm Schistosoma mansoni. This protein has been detected with antibodies in all stages of the parasite found in the human host, notably the lung stage, and therefore is of interest as a vaccine candidate. In addition SM23 has been shown to be a member of a proposed new superfamily of membrane proteins whose structures do not conform to the previously known classifications. To date there are 13 members including ME491 (CD63, Pltgp40), CD9 (p23), TAPA-1, CD37, CD53, MRC OX-44, CO-029, MRP-1, L6, the gene product of TI-1, the target of mAb AD-1, SM23, and SJ23 (the Schistosoma japonicum homologue). Most of these molecules except for those in the two blood vessel-dwelling parasites are found in membranes of hemopoietic and/or malignant cells and all have unknown function. In this study we used recombinantly expressed full-length and partial molecules as well as synthesized peptides to map T cell and B cell epitopes of SM23. The two predicted external hydrophilic domains were found to be highly immunogenic and contained several B cell epitopes. There were at least four T cell epitopes in the large hydrophilic domain. One segment of 23 amino acids contained both a T cell and B cell epitope as well as the putative glycosylation site. This particular segment was recognized by immune sera and cells of every mouse strain tested. The elucidation of these epitopes demonstrates the immunogenic nature of this molecule and raises questions as to the role of SM23 in the host/parasite relationship.", "contents": "T and B cell epitope mapping of SM23, an integral membrane protein of Schistosoma mansoni. SM23 is an integral membrane protein of the blood-vessel dwelling parasitic worm Schistosoma mansoni. This protein has been detected with antibodies in all stages of the parasite found in the human host, notably the lung stage, and therefore is of interest as a vaccine candidate. In addition SM23 has been shown to be a member of a proposed new superfamily of membrane proteins whose structures do not conform to the previously known classifications. To date there are 13 members including ME491 (CD63, Pltgp40), CD9 (p23), TAPA-1, CD37, CD53, MRC OX-44, CO-029, MRP-1, L6, the gene product of TI-1, the target of mAb AD-1, SM23, and SJ23 (the Schistosoma japonicum homologue). Most of these molecules except for those in the two blood vessel-dwelling parasites are found in membranes of hemopoietic and/or malignant cells and all have unknown function. In this study we used recombinantly expressed full-length and partial molecules as well as synthesized peptides to map T cell and B cell epitopes of SM23. The two predicted external hydrophilic domains were found to be highly immunogenic and contained several B cell epitopes. There were at least four T cell epitopes in the large hydrophilic domain. One segment of 23 amino acids contained both a T cell and B cell epitope as well as the putative glycosylation site. This particular segment was recognized by immune sera and cells of every mouse strain tested. The elucidation of these epitopes demonstrates the immunogenic nature of this molecule and raises questions as to the role of SM23 in the host/parasite relationship."} {"id": "PMID:1281198", "title": "Role of colony-stimulating factor-1 in macrophage activation in tumor-bearing mice.", "content": "We previously reported a dramatically increased number of macrophages in tumor-bearing mice. In this study, we investigated the involvement of CSF in that phenomenon. CSF-1 responding cells as macrophages precursors increased significantly in number in the spleens of tumor-bearing mice as compared with those in normal mice. Splenic cells and sera from the tumor-bearing mice respectively expressed CSF-1 in mRNA and serum protein levels, but failed to express the other CSF (granulocyte-macrophage-CSF or IL-3). Nonadherent splenic mononuclear cells (< 0.5% macrophages) from normal mice proliferated and differentiated into mature macrophages in culture within 7 days with recombinant mouse CSF-1 (rCSF-1). Both macrophages harvested from tumor-bearing mice and those activated in vitro with rCSF-1 expressed mostly Mac-1, -2 (and -3) Ag, showed yeast phagocytosis, produced IL-1 but not IL-2 or IL-3, and displayed potent cytotoxicity against NK cell resistant Meth-A tumor cells. These macrophages also expressed lipocortin I mRNA and secreted lipocortin I protein, and suppressed mitogenic responses of splenic lymphocytes. rCSF-1-activated macrophages derived from nonadherent splenic cells expressed both CSF-1 and CSF-1 receptor (c-fms) mRNA. Administration of rCSF-1 into normal mice induced hemopoietic and immunologic alternations similar to those observed in tumor-bearing mice. These results suggest that CSF-1 is involved in the dramatic increase of macrophages in tumor-bearing mice, possibly through an autocrine or paracrine loop.", "contents": "Role of colony-stimulating factor-1 in macrophage activation in tumor-bearing mice. We previously reported a dramatically increased number of macrophages in tumor-bearing mice. In this study, we investigated the involvement of CSF in that phenomenon. CSF-1 responding cells as macrophages precursors increased significantly in number in the spleens of tumor-bearing mice as compared with those in normal mice. Splenic cells and sera from the tumor-bearing mice respectively expressed CSF-1 in mRNA and serum protein levels, but failed to express the other CSF (granulocyte-macrophage-CSF or IL-3). Nonadherent splenic mononuclear cells (< 0.5% macrophages) from normal mice proliferated and differentiated into mature macrophages in culture within 7 days with recombinant mouse CSF-1 (rCSF-1). Both macrophages harvested from tumor-bearing mice and those activated in vitro with rCSF-1 expressed mostly Mac-1, -2 (and -3) Ag, showed yeast phagocytosis, produced IL-1 but not IL-2 or IL-3, and displayed potent cytotoxicity against NK cell resistant Meth-A tumor cells. These macrophages also expressed lipocortin I mRNA and secreted lipocortin I protein, and suppressed mitogenic responses of splenic lymphocytes. rCSF-1-activated macrophages derived from nonadherent splenic cells expressed both CSF-1 and CSF-1 receptor (c-fms) mRNA. Administration of rCSF-1 into normal mice induced hemopoietic and immunologic alternations similar to those observed in tumor-bearing mice. These results suggest that CSF-1 is involved in the dramatic increase of macrophages in tumor-bearing mice, possibly through an autocrine or paracrine loop."} {"id": "PMID:1281199", "title": "Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells.", "content": "One of the key features associated with programmed cell death in many tissues is the phagocytosis of apoptotic bodies by macrophages. Removal of apoptotic cells occurs before their lysis, indicating that these cells, during the development of apoptosis, express specific surface changes recognized by macrophages. We have compared the mechanisms by which four different macrophage populations recognize apoptotic cells. Murine macrophages elicited into the peritoneal cavity with either of two different phlogistic agents were able to phagocytose apoptotic cells. This phagocytosis was inhibited by phosphatidylserine (PS), regardless of the species (human or murine) or type (lymphocyte or neutrophil) of the apoptotic cell. In contrast, the murine bone marrow macrophage, like the human monocyte-derived macrophage, utilized the vitronectin receptor, an alpha v beta 3 integrin, for the removal of apoptotic cells, regardless of their species or type. That human macrophages are capable, under some circumstances, of recognizing PS on apoptotic cells was suggested by the observation that PS liposomes inhibited phagocytosis by phorbol ester-treated THP-1 cells. These results suggest that the mechanism by which apoptotic cells are recognized and phagocytosed by macrophages is determined by the subpopulation of macrophages studied.", "contents": "Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. One of the key features associated with programmed cell death in many tissues is the phagocytosis of apoptotic bodies by macrophages. Removal of apoptotic cells occurs before their lysis, indicating that these cells, during the development of apoptosis, express specific surface changes recognized by macrophages. We have compared the mechanisms by which four different macrophage populations recognize apoptotic cells. Murine macrophages elicited into the peritoneal cavity with either of two different phlogistic agents were able to phagocytose apoptotic cells. This phagocytosis was inhibited by phosphatidylserine (PS), regardless of the species (human or murine) or type (lymphocyte or neutrophil) of the apoptotic cell. In contrast, the murine bone marrow macrophage, like the human monocyte-derived macrophage, utilized the vitronectin receptor, an alpha v beta 3 integrin, for the removal of apoptotic cells, regardless of their species or type. That human macrophages are capable, under some circumstances, of recognizing PS on apoptotic cells was suggested by the observation that PS liposomes inhibited phagocytosis by phorbol ester-treated THP-1 cells. These results suggest that the mechanism by which apoptotic cells are recognized and phagocytosed by macrophages is determined by the subpopulation of macrophages studied."} {"id": "PMID:1281200", "title": "IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis.", "content": "About 30% of patients suffering from the chronic autoimmune liver disease primary biliary cirrhosis produce autoantibodies against Sp100, a protein migrating in SDS-PAGE at a position corresponding to 100 kDa and located on discrete dot-shaped nuclear structures. The human Sp100 cDNA has recently been cloned and the deduced amino acid sequence was found to contain similarities to several transcriptional regulatory proteins; the biologic function of the Sp100 protein, however, is still unknown. In this study we present data which show that infection of HEp2 cells with influenza A virus, transformation of glial cells with SV40 DNA, and stimulation of PBL with mitogens affect the expression of the Sp100 autoantigen. These observations prompted us to investigate whether expression of the Sp100 protein is modulated by the action of IFN. Immunofluorescence staining of HEp2 and HeLa cells grown in the presence of IFN-alpha, IFN-beta, or IFN-gamma revealed an increase both in size and number of the Sp100 protein-containing nuclear dots, whereas no such effect was observed with cells treated with TNF-alpha. As measured by an immunoblot-based ELISA the amount of Sp100 protein in INF-beta-treated cells (1000 IU/ml, 18 h) was eight to nine times higher than in untreated cells. The enhanced protein expression was accompanied by an accumulation of the Sp100-specific mRNA (13-fold increase of the normal level after 10 h of INF-beta treatment of HEp2 cells). These findings characterize the Sp100 protein as a new member of IFN-modulated proteins and raise the question whether cytokine-mediated increase of Sp100 protein expression plays a role in induction of anti-Sp100 autoantibodies.", "contents": "IFN enhance expression of Sp100, an autoantigen in primary biliary cirrhosis. About 30% of patients suffering from the chronic autoimmune liver disease primary biliary cirrhosis produce autoantibodies against Sp100, a protein migrating in SDS-PAGE at a position corresponding to 100 kDa and located on discrete dot-shaped nuclear structures. The human Sp100 cDNA has recently been cloned and the deduced amino acid sequence was found to contain similarities to several transcriptional regulatory proteins; the biologic function of the Sp100 protein, however, is still unknown. In this study we present data which show that infection of HEp2 cells with influenza A virus, transformation of glial cells with SV40 DNA, and stimulation of PBL with mitogens affect the expression of the Sp100 autoantigen. These observations prompted us to investigate whether expression of the Sp100 protein is modulated by the action of IFN. Immunofluorescence staining of HEp2 and HeLa cells grown in the presence of IFN-alpha, IFN-beta, or IFN-gamma revealed an increase both in size and number of the Sp100 protein-containing nuclear dots, whereas no such effect was observed with cells treated with TNF-alpha. As measured by an immunoblot-based ELISA the amount of Sp100 protein in INF-beta-treated cells (1000 IU/ml, 18 h) was eight to nine times higher than in untreated cells. The enhanced protein expression was accompanied by an accumulation of the Sp100-specific mRNA (13-fold increase of the normal level after 10 h of INF-beta treatment of HEp2 cells). These findings characterize the Sp100 protein as a new member of IFN-modulated proteins and raise the question whether cytokine-mediated increase of Sp100 protein expression plays a role in induction of anti-Sp100 autoantibodies."} {"id": "PMID:1281201", "title": "Human bone marrow stromal cell lines from myeloma and rheumatoid arthritis that can support murine pre-B cell growth.", "content": "In order to elucidate the pathologic significance of the bone marrow (BM) microenvironment in multiple myeloma (MM) and rheumatoid arthritis (RA), we established patient- or healthy donor (HD)-derived BM stromal cell lines by transfecting the plasmid for expression of SV40 large T Ag and examined their ability to support the stromal cell-dependent growth of a pre-B cell line, DW34. The means of recovered cell numbers of DW34 co-cultured with MM- and RA-derived BM stromal cell lines ranged from 6- to 10-fold more than those with HD-derived ones. Their enhanced ability to support DW34 cell growth was not caused by cytokines, including IL-6, IL-7, and c-kit ligand, although exogenous IL-7 could augment the growth-supporting ability. DW34 cell growth on the stromal cell lines was abolished by inhibiting cell-to-cell interaction with a membrane filter. FACS analysis revealed that the stromal cell lines did not express LFA-1 alpha, beta, NCAM, or ELAM-1. Both patient and HD BM stromal cell lines variably expressed ICAM-1, VCAM-1, and CD44. However, surface expression levels of these molecules did not correlate with the ability of the stromal cell lines to support DW34 cell growth. Taken together, these results suggested that BM microenvironment might play important roles in the pathogenesis of MM and RA.", "contents": "Human bone marrow stromal cell lines from myeloma and rheumatoid arthritis that can support murine pre-B cell growth. In order to elucidate the pathologic significance of the bone marrow (BM) microenvironment in multiple myeloma (MM) and rheumatoid arthritis (RA), we established patient- or healthy donor (HD)-derived BM stromal cell lines by transfecting the plasmid for expression of SV40 large T Ag and examined their ability to support the stromal cell-dependent growth of a pre-B cell line, DW34. The means of recovered cell numbers of DW34 co-cultured with MM- and RA-derived BM stromal cell lines ranged from 6- to 10-fold more than those with HD-derived ones. Their enhanced ability to support DW34 cell growth was not caused by cytokines, including IL-6, IL-7, and c-kit ligand, although exogenous IL-7 could augment the growth-supporting ability. DW34 cell growth on the stromal cell lines was abolished by inhibiting cell-to-cell interaction with a membrane filter. FACS analysis revealed that the stromal cell lines did not express LFA-1 alpha, beta, NCAM, or ELAM-1. Both patient and HD BM stromal cell lines variably expressed ICAM-1, VCAM-1, and CD44. However, surface expression levels of these molecules did not correlate with the ability of the stromal cell lines to support DW34 cell growth. Taken together, these results suggested that BM microenvironment might play important roles in the pathogenesis of MM and RA."} {"id": "PMID:1281202", "title": "CD4 activation of HIV fusion.", "content": "The primary cellular receptor for the human immunodeficiency viruses type 1 (HIV-1) and type 2 (HIV-2) is the CD4 antigen. HIV infection of CD4+ cells is initiated by binding of the virus to the cell surface, via a high affinity interaction between CD4 and the HIV outer envelope glycoprotein, gp120. The development of model systems using soluble recombinant forms of CD4 (sCD4) has allowed kinetic and thermodynamic analyses of CD4 binding to gp120, and study of the post-binding events leading to virus-cell membrane fusion. It has thus been demonstrated that the affinity of sCD4 for gp120 on virions or HIV-infected cells depends on both the primary sequence and the tertiary structure of gp120 in the membrane. With cell-line adapted isolates of HIV-1, sCD4 binding induces conformational changes in gp120, leading to the complete dissociation of gp120 from the transmembrane glycoprotein, gp41, and exposing cryptic epitopes of gp41. Similar observations have been made with cell-anchored CD4; exposure of cryptic gp41 epitopes occurs at the fusion interface between clusters of CD4-expressing and HIV-infected cells. Thus, for HIV-1, CD4 induces exposure of fusogenic components of gp41 which triggers virus-cell membrane coalescence. This is termed receptor-mediated activation of fusion. With primary isolates of HIV-1 and the related lentiviruses, HIV-2 and simian immunodeficiency virus (SIV), the CD4-induced molecular rearrangements in gp120 are more subtle, implying that there is a spectrum of responses to sCD4 binding. The high-affinity binding site on CD4 for gp120 is necessary and probably sufficient for activation of HIV fusion, although other regions of CD4 may indirectly influence viral entry. There are two regions on the envelope glycoproteins which are recognized as playing a role in HIV entry: the N-terminus of gp41 and the gp120 V3 loop. The roles of these domains are discussed.", "contents": "CD4 activation of HIV fusion. The primary cellular receptor for the human immunodeficiency viruses type 1 (HIV-1) and type 2 (HIV-2) is the CD4 antigen. HIV infection of CD4+ cells is initiated by binding of the virus to the cell surface, via a high affinity interaction between CD4 and the HIV outer envelope glycoprotein, gp120. The development of model systems using soluble recombinant forms of CD4 (sCD4) has allowed kinetic and thermodynamic analyses of CD4 binding to gp120, and study of the post-binding events leading to virus-cell membrane fusion. It has thus been demonstrated that the affinity of sCD4 for gp120 on virions or HIV-infected cells depends on both the primary sequence and the tertiary structure of gp120 in the membrane. With cell-line adapted isolates of HIV-1, sCD4 binding induces conformational changes in gp120, leading to the complete dissociation of gp120 from the transmembrane glycoprotein, gp41, and exposing cryptic epitopes of gp41. Similar observations have been made with cell-anchored CD4; exposure of cryptic gp41 epitopes occurs at the fusion interface between clusters of CD4-expressing and HIV-infected cells. Thus, for HIV-1, CD4 induces exposure of fusogenic components of gp41 which triggers virus-cell membrane coalescence. This is termed receptor-mediated activation of fusion. With primary isolates of HIV-1 and the related lentiviruses, HIV-2 and simian immunodeficiency virus (SIV), the CD4-induced molecular rearrangements in gp120 are more subtle, implying that there is a spectrum of responses to sCD4 binding. The high-affinity binding site on CD4 for gp120 is necessary and probably sufficient for activation of HIV fusion, although other regions of CD4 may indirectly influence viral entry. There are two regions on the envelope glycoproteins which are recognized as playing a role in HIV entry: the N-terminus of gp41 and the gp120 V3 loop. The roles of these domains are discussed."} {"id": "PMID:1281203", "title": "Histochemical and immunocytochemical characterizations of laminated bodies in the pancreas acinar lumen.", "content": "Combined adrenalectomy and castration cause numerous morphological alterations in the exocrine pancreas of the rat. Accumulation of laminated bodies (LB) in the acinar lumen is one of these alterations. A series of classical histological stains was applied to identify the components of these structures. A positive reaction was observed with periodic acid-Schiff, Congo red, and Alcian blue (pH 2.5). The first stain reacts with neutral and some acid mucosubstances and the second with amyloid, whereas the last one reacts with sulfated and nonsulfated acid mucosubstances. The LB also responded to Luxol fast blue, indicating the presence of lipids, an observation that is in agreement with the osmiophilic properties of these structures. A more specific identification of LB components was carried out with the immunocytochemical protein A-gold technique. Presence of gamma-glutamyltranspeptidase (gamma-GT) and GP2, two glycoproteins known to be secreted by the pancreas, was tested. The gamma-GT was associated with LB whereas GP2 was found in the lumen but not associated with these structures. Amylase was undetectable when LB occupied the lumen, suggesting that the process leading to production of LB also blocks secretory activity. To determine if diet influences LB accumulation in the pancreas acinar lumen, their frequency was compared in rats fed Purina Lab Chow or a lipid-free synthetic diet. A significant increase was observed in castrated-adrenalectomized rats fed the latter diet. This increase corresponded to a pronounced reduction in the number of zymogen granules (ZG) in the acinar cell. Our results show that LB are made of lipids, neutral mucosubstances, and nonsulfated acid mucosubstances, and that hormonal (steroids) and dietary factors (lipids) influence their accumulation.", "contents": "Histochemical and immunocytochemical characterizations of laminated bodies in the pancreas acinar lumen. Combined adrenalectomy and castration cause numerous morphological alterations in the exocrine pancreas of the rat. Accumulation of laminated bodies (LB) in the acinar lumen is one of these alterations. A series of classical histological stains was applied to identify the components of these structures. A positive reaction was observed with periodic acid-Schiff, Congo red, and Alcian blue (pH 2.5). The first stain reacts with neutral and some acid mucosubstances and the second with amyloid, whereas the last one reacts with sulfated and nonsulfated acid mucosubstances. The LB also responded to Luxol fast blue, indicating the presence of lipids, an observation that is in agreement with the osmiophilic properties of these structures. A more specific identification of LB components was carried out with the immunocytochemical protein A-gold technique. Presence of gamma-glutamyltranspeptidase (gamma-GT) and GP2, two glycoproteins known to be secreted by the pancreas, was tested. The gamma-GT was associated with LB whereas GP2 was found in the lumen but not associated with these structures. Amylase was undetectable when LB occupied the lumen, suggesting that the process leading to production of LB also blocks secretory activity. To determine if diet influences LB accumulation in the pancreas acinar lumen, their frequency was compared in rats fed Purina Lab Chow or a lipid-free synthetic diet. A significant increase was observed in castrated-adrenalectomized rats fed the latter diet. This increase corresponded to a pronounced reduction in the number of zymogen granules (ZG) in the acinar cell. Our results show that LB are made of lipids, neutral mucosubstances, and nonsulfated acid mucosubstances, and that hormonal (steroids) and dietary factors (lipids) influence their accumulation."} {"id": "PMID:1281204", "title": "Protective effect of nafamostat mesilate on cellular and lysosomal fragility of acinar cells in rat cerulein pancreatitis.", "content": "This in vivo and in vitro study demonstrates the protective effects of a new synthetic protease inhibitor--nafamostat mesilate, FUT-175--on increased cellular and lysosomal fragility within acinar cells during the early stage of cerulein-induced acute pancreatitis in rats. FUT-175 prevented hyperamylasemia, pancreatic edema, congestion owing to amylase, and lactic dehydrogenase (LDH) discharge from acini as well as cathepsin-B leakage from lysosomes dose-dependently in doses of 1-10 mg/kg.h. These results suggest that FUT-175 can protect against pancreatitis at subcellular levels in lysosomes and cellular or organelle membranes. Proteases may well play the important role in the pathogenesis of acute pancreatitis, and such a low molecular protease inhibitor may be useful clinically in the treatment of acute pancreatitis.", "contents": "Protective effect of nafamostat mesilate on cellular and lysosomal fragility of acinar cells in rat cerulein pancreatitis. This in vivo and in vitro study demonstrates the protective effects of a new synthetic protease inhibitor--nafamostat mesilate, FUT-175--on increased cellular and lysosomal fragility within acinar cells during the early stage of cerulein-induced acute pancreatitis in rats. FUT-175 prevented hyperamylasemia, pancreatic edema, congestion owing to amylase, and lactic dehydrogenase (LDH) discharge from acini as well as cathepsin-B leakage from lysosomes dose-dependently in doses of 1-10 mg/kg.h. These results suggest that FUT-175 can protect against pancreatitis at subcellular levels in lysosomes and cellular or organelle membranes. Proteases may well play the important role in the pathogenesis of acute pancreatitis, and such a low molecular protease inhibitor may be useful clinically in the treatment of acute pancreatitis."} {"id": "PMID:1281205", "title": "Haemodilution in patients with peripheral arterial occlusive disease.", "content": "Haemodilution is an efficient conservative therapy of peripheral arterial occlusive disease. Already a single isovolaemic haemodilution (replacement of 500 ml blood for Haes* 0.5, 10%) increases the pain-free walking distance by 85%. These effects can be maintained by a constant therapy over six weeks and following haemodilution once or twice per month. The haematocrit values should be between 38 and 42%. The haemodilution should be done hyper- or isovolaemically. Not more than 250 ml blood and 500 ml Haes should be infused during one session in order to avoid hypovolaemia. This means an infusion of 250 ml Haes, venesection of 250 ml blood via the same access and then infusion of the remaining 250 ml. The whole procedure should not last more than one hour. Blood pressure, heart rate, lung auscultation and percussion as well as creatinine values has to be controlled during an intensive therapy. If the hydroxyethyl starch concentration exceeds 150 g per week pruritus may occur in singular cases, if the concentration exceeds 700 g per week it is observed in 50% of the cases. Provided the preventive measures are observed haemodilution is an efficient and good therapy which also increases the compliance to practice vascular exercise.", "contents": "Haemodilution in patients with peripheral arterial occlusive disease. Haemodilution is an efficient conservative therapy of peripheral arterial occlusive disease. Already a single isovolaemic haemodilution (replacement of 500 ml blood for Haes* 0.5, 10%) increases the pain-free walking distance by 85%. These effects can be maintained by a constant therapy over six weeks and following haemodilution once or twice per month. The haematocrit values should be between 38 and 42%. The haemodilution should be done hyper- or isovolaemically. Not more than 250 ml blood and 500 ml Haes should be infused during one session in order to avoid hypovolaemia. This means an infusion of 250 ml Haes, venesection of 250 ml blood via the same access and then infusion of the remaining 250 ml. The whole procedure should not last more than one hour. Blood pressure, heart rate, lung auscultation and percussion as well as creatinine values has to be controlled during an intensive therapy. If the hydroxyethyl starch concentration exceeds 150 g per week pruritus may occur in singular cases, if the concentration exceeds 700 g per week it is observed in 50% of the cases. Provided the preventive measures are observed haemodilution is an efficient and good therapy which also increases the compliance to practice vascular exercise."} {"id": "PMID:1281207", "title": "RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes.", "content": "The cellular infiltrates of certain inflammatory processes found in parasitic infection or in allergic diseases consist predominantly of eosinophilic granulocytes, often in association with activated T cells. This suggests the existence of chemotactic agonists specific for eosinophils and lymphocyte subsets devoid of neutrophil-activating properties. We therefore examined four members of the intercrine/chemokine superfamily of cytokines (monocyte chemotactic peptide 1 [MCP-1], RANTES, macrophage inflammatory protein 1 alpha [MIP-1 alpha], and MIP-1 beta), which do not activate neutrophils, for their ability to affect different eosinophil effector functions. RANTES strongly attracted normal human eosinophils by a chemotactic rather than a chemokinetic mechanism with a similar efficacy as the most potent chemotactic myeloid cell agonist, C5a. MIP-1 alpha also induced eosinophil migration, however, with lower efficacy. RANTES and MIP-1 alpha induced eosinophil cationic protein release in cytochalasin B-treated eosinophils, but did not promote leukotriene C4 formation by eosinophils, even after preincubation with interleukin 3 (IL-3), in contrast to other chemotactic agonists such as C5a and formyl-methionyl-leucyl-phenylalanine (FMLP). RANTES, but not MIP-1 alpha, induced a biphasic chemiluminescence response, however, of lower magnitude than C5a. RANTES and MIP-1 alpha both promoted identical transient changes in intracellular free calcium concentration ([Ca2+]i), with kinetics similar to those induced by chemotactic peptides known to interact with G protein-coupled receptors. No cross-desensitization towards other peptide agonists (e.g., C5a, IL-8, FMLP) was observed, suggesting the presence of specific receptors. Despite its weaker eosinophil-activating properties, MIP-1 alpha was at least 10 times more potent on a molar basis than RANTES at inducing [Ca2+]i changes. Interestingly, RANTES deactivated the MIP-1 alpha-induced [Ca2+]i changes, while the RANTES response was preserved after MIP-1 alpha stimulation. MCP-1, a potent monocyte chemoattractant and basophil agonist, as well as MIP-1 beta, a peptide with pronounced homology to MIP-1 alpha, did not activate the eosinophil functions tested. Our results indicate that RANTES and MIP-1 alpha are crucial mediators of inflammatory processes in which eosinophils predominate.", "contents": "RANTES and macrophage inflammatory protein 1 alpha induce the migration and activation of normal human eosinophil granulocytes. The cellular infiltrates of certain inflammatory processes found in parasitic infection or in allergic diseases consist predominantly of eosinophilic granulocytes, often in association with activated T cells. This suggests the existence of chemotactic agonists specific for eosinophils and lymphocyte subsets devoid of neutrophil-activating properties. We therefore examined four members of the intercrine/chemokine superfamily of cytokines (monocyte chemotactic peptide 1 [MCP-1], RANTES, macrophage inflammatory protein 1 alpha [MIP-1 alpha], and MIP-1 beta), which do not activate neutrophils, for their ability to affect different eosinophil effector functions. RANTES strongly attracted normal human eosinophils by a chemotactic rather than a chemokinetic mechanism with a similar efficacy as the most potent chemotactic myeloid cell agonist, C5a. MIP-1 alpha also induced eosinophil migration, however, with lower efficacy. RANTES and MIP-1 alpha induced eosinophil cationic protein release in cytochalasin B-treated eosinophils, but did not promote leukotriene C4 formation by eosinophils, even after preincubation with interleukin 3 (IL-3), in contrast to other chemotactic agonists such as C5a and formyl-methionyl-leucyl-phenylalanine (FMLP). RANTES, but not MIP-1 alpha, induced a biphasic chemiluminescence response, however, of lower magnitude than C5a. RANTES and MIP-1 alpha both promoted identical transient changes in intracellular free calcium concentration ([Ca2+]i), with kinetics similar to those induced by chemotactic peptides known to interact with G protein-coupled receptors. No cross-desensitization towards other peptide agonists (e.g., C5a, IL-8, FMLP) was observed, suggesting the presence of specific receptors. Despite its weaker eosinophil-activating properties, MIP-1 alpha was at least 10 times more potent on a molar basis than RANTES at inducing [Ca2+]i changes. Interestingly, RANTES deactivated the MIP-1 alpha-induced [Ca2+]i changes, while the RANTES response was preserved after MIP-1 alpha stimulation. MCP-1, a potent monocyte chemoattractant and basophil agonist, as well as MIP-1 beta, a peptide with pronounced homology to MIP-1 alpha, did not activate the eosinophil functions tested. Our results indicate that RANTES and MIP-1 alpha are crucial mediators of inflammatory processes in which eosinophils predominate."} {"id": "PMID:1281208", "title": "Thymus reconstitution by c-kit-expressing hematopoietic stem cells purified from adult mouse bone marrow.", "content": "The introduction of clonal assays and long-term culture systems has resulted in considerable progress in the understanding of the early events that control self-renewal and commitment to differentiation of pluripotent hematopoietic stem cells (PHSC). Relatively little is known about the factors that control the commitment of PHSC to the lymphoid lineages, especially the T cell lineage. In the present study, the expression of the proto-oncogene c-kit was used to isolate and study the capacity of highly purified day 14 colony-forming units-spleen (CFU-S) to reconstitute the thymus of sublethally irradiated Thy-1 congenic recipient mice. We demonstrate here that one c-kit positive (c-kitpos) stem cell upon intrathymic transfer can effectively reconstitute the thymus of a sublethally irradiated recipient. After a lag phase of 15 d, high levels of donor-derived thymocytes (Thy-1.1pos) could be detected until 65 d after transplantation in Thy-1.2pos host mice. Donor-derived cells were only detected in the lobe of the thymus in which cells were previously injected and not in the noninjected lobe. These data suggest that c-kitpos stem cells do not migrate from one lobe to another and that they do not re-seed the thymus after having migrated to the bone marrow. The level and duration of reconstitution was found to be cell dose dependent, suggesting that, over time, endogenous stem cells compete with donor stem cells for available sites in the thymus microenvironment. The data presented in this paper demonstrate that commitment of purified adult bone marrow-derived c-kitpos stem cells to the T cell differentiation pathway can occur in the thymus and does not have to happen in the bone marrow.", "contents": "Thymus reconstitution by c-kit-expressing hematopoietic stem cells purified from adult mouse bone marrow. The introduction of clonal assays and long-term culture systems has resulted in considerable progress in the understanding of the early events that control self-renewal and commitment to differentiation of pluripotent hematopoietic stem cells (PHSC). Relatively little is known about the factors that control the commitment of PHSC to the lymphoid lineages, especially the T cell lineage. In the present study, the expression of the proto-oncogene c-kit was used to isolate and study the capacity of highly purified day 14 colony-forming units-spleen (CFU-S) to reconstitute the thymus of sublethally irradiated Thy-1 congenic recipient mice. We demonstrate here that one c-kit positive (c-kitpos) stem cell upon intrathymic transfer can effectively reconstitute the thymus of a sublethally irradiated recipient. After a lag phase of 15 d, high levels of donor-derived thymocytes (Thy-1.1pos) could be detected until 65 d after transplantation in Thy-1.2pos host mice. Donor-derived cells were only detected in the lobe of the thymus in which cells were previously injected and not in the noninjected lobe. These data suggest that c-kitpos stem cells do not migrate from one lobe to another and that they do not re-seed the thymus after having migrated to the bone marrow. The level and duration of reconstitution was found to be cell dose dependent, suggesting that, over time, endogenous stem cells compete with donor stem cells for available sites in the thymus microenvironment. The data presented in this paper demonstrate that commitment of purified adult bone marrow-derived c-kitpos stem cells to the T cell differentiation pathway can occur in the thymus and does not have to happen in the bone marrow."} {"id": "PMID:1281209", "title": "Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion.", "content": "Signaling through the cell surface molecule, CD40, is known to play an important role in the proliferation and differentiation of B lymphocytes. Using the thymoma cell line EL4, we recently identified and cloned a cDNA encoding a murine ligand for the CD40 molecule (mCD40-L) and showed that it has biological activity in vitro. A cDNA encoding a human homologue of the mCD40-L was isolated using crosshybridization techniques from an activated peripheral blood T cell library. The predicted amino acid sequence indicates that this human ligand for CD40 (hCD40-L) is a 261 amino acid type II membrane protein that exhibits 78% amino acid identity with its murine counterpart. Northern blot and FACS analyses suggest that the hCD40-L is restricted in its expression to T lymphocytes, and that it is most abundant on the CD4+ T cell subpopulation. Cells transfected with hCD40-L caused the proliferation of human tonsil B cells in the absence of costimuli and, in the presence of interleukin 4, induced immunoglobulin E secretion from purified human B cells. A comparison of the efficacy of the hCD40-L and mCD40-L in these assays is presented.", "contents": "Recombinant human CD40 ligand stimulates B cell proliferation and immunoglobulin E secretion. Signaling through the cell surface molecule, CD40, is known to play an important role in the proliferation and differentiation of B lymphocytes. Using the thymoma cell line EL4, we recently identified and cloned a cDNA encoding a murine ligand for the CD40 molecule (mCD40-L) and showed that it has biological activity in vitro. A cDNA encoding a human homologue of the mCD40-L was isolated using crosshybridization techniques from an activated peripheral blood T cell library. The predicted amino acid sequence indicates that this human ligand for CD40 (hCD40-L) is a 261 amino acid type II membrane protein that exhibits 78% amino acid identity with its murine counterpart. Northern blot and FACS analyses suggest that the hCD40-L is restricted in its expression to T lymphocytes, and that it is most abundant on the CD4+ T cell subpopulation. Cells transfected with hCD40-L caused the proliferation of human tonsil B cells in the absence of costimuli and, in the presence of interleukin 4, induced immunoglobulin E secretion from purified human B cells. A comparison of the efficacy of the hCD40-L and mCD40-L in these assays is presented."} {"id": "PMID:1281210", "title": "The contribution of increased collagen synthesis to human glomerulosclerosis: a quantitative analysis of alpha 2IV collagen mRNA expression by competitive polymerase chain reaction.", "content": "We previously reported that one of the main components of the sclerotic material in human glomerular diseases was type IV collagen. In this study we examined the contribution of increased synthesis to this process at the gene expression level. Sufficient material has not been available to study type IV collagen synthesis by normal or sclerotic glomeruli in humans. We took advantage of the availability of nephrectomy specimens from patients with renal carcinoma, and of the observation that approximately 50% of these patients develop varying degrees of glomerulosclerosis. We microdissected glomeruli from 10 patients and analyzed them using in situ reverse transcription coupled with polymerase chain reaction (PCR) analyses (in situ RT-PCR). alpha 2IV collagen mRNA, after reverse transcription into cDNA, was detected in all patients and appeared to be increased in those with glomerulosclerosis (n = 5). A competitive PCR assay was developed to quantitate this change. There was an average 3.7-fold increase in glomerular type IV collagen cDNA in patients with significant sclerosis. This change was not due to an increased number of glomerular cells. Thus, glomerulosclerosis in humans is associated with an elevation of glomerular type IV collagen gene expression, suggesting that increased synthesis of type IV collagen may represent one component of this process.", "contents": "The contribution of increased collagen synthesis to human glomerulosclerosis: a quantitative analysis of alpha 2IV collagen mRNA expression by competitive polymerase chain reaction. We previously reported that one of the main components of the sclerotic material in human glomerular diseases was type IV collagen. In this study we examined the contribution of increased synthesis to this process at the gene expression level. Sufficient material has not been available to study type IV collagen synthesis by normal or sclerotic glomeruli in humans. We took advantage of the availability of nephrectomy specimens from patients with renal carcinoma, and of the observation that approximately 50% of these patients develop varying degrees of glomerulosclerosis. We microdissected glomeruli from 10 patients and analyzed them using in situ reverse transcription coupled with polymerase chain reaction (PCR) analyses (in situ RT-PCR). alpha 2IV collagen mRNA, after reverse transcription into cDNA, was detected in all patients and appeared to be increased in those with glomerulosclerosis (n = 5). A competitive PCR assay was developed to quantitate this change. There was an average 3.7-fold increase in glomerular type IV collagen cDNA in patients with significant sclerosis. This change was not due to an increased number of glomerular cells. Thus, glomerulosclerosis in humans is associated with an elevation of glomerular type IV collagen gene expression, suggesting that increased synthesis of type IV collagen may represent one component of this process."} {"id": "PMID:1281211", "title": "Functional analysis of the human vascular cell adhesion molecule 1 promoter.", "content": "The vascular cell adhesion molecule 1 (VCAM-1) is a 110-kD member of the immunoglobulin gene superfamily expressed on the surface of interleukin 1 beta- or tumor necrosis factor alpha (TNF)-stimulated endothelial cells. The cell surface protein functions as an inducible adhesion receptor for circulating mononuclear leukocytes and some tumor cells. We have previously characterized the genomic organization of the VCAM1 gene and described its chromosomal localization. In this report, the promoter of the VCAM1 gene is characterized. New transcription of the VCAM1 gene occurred when endothelial cells were treated with TNF. Fusion plasmids containing the 5' flanking sequence of the VCAM1 gene and the chloramphenicol acetyltransferase reporter gene were used to identify cis-acting sequences that direct the cytokine-induced transcription. When transfected into bovine aortic endothelial cells, constructs containing 755 bp of the 5' flanking sequence were induced by TNF. Within the cytokine-responsive region of the core promoter were functional NF-kappa B and GATA elements. Upstream of the core promoter, the VCAM1 5' flanking sequence contained a negative regulatory activity. NF-kappa B-mediated activation of VCAM1 gene expression may lead to endothelial expression of a mononuclear leukocyte adhesion molecule associated with initial events in the development of an atherosclerotic lesion.", "contents": "Functional analysis of the human vascular cell adhesion molecule 1 promoter. The vascular cell adhesion molecule 1 (VCAM-1) is a 110-kD member of the immunoglobulin gene superfamily expressed on the surface of interleukin 1 beta- or tumor necrosis factor alpha (TNF)-stimulated endothelial cells. The cell surface protein functions as an inducible adhesion receptor for circulating mononuclear leukocytes and some tumor cells. We have previously characterized the genomic organization of the VCAM1 gene and described its chromosomal localization. In this report, the promoter of the VCAM1 gene is characterized. New transcription of the VCAM1 gene occurred when endothelial cells were treated with TNF. Fusion plasmids containing the 5' flanking sequence of the VCAM1 gene and the chloramphenicol acetyltransferase reporter gene were used to identify cis-acting sequences that direct the cytokine-induced transcription. When transfected into bovine aortic endothelial cells, constructs containing 755 bp of the 5' flanking sequence were induced by TNF. Within the cytokine-responsive region of the core promoter were functional NF-kappa B and GATA elements. Upstream of the core promoter, the VCAM1 5' flanking sequence contained a negative regulatory activity. NF-kappa B-mediated activation of VCAM1 gene expression may lead to endothelial expression of a mononuclear leukocyte adhesion molecule associated with initial events in the development of an atherosclerotic lesion."} {"id": "PMID:1281212", "title": "Major histocompatibility complex conformational epitopes are peptide specific.", "content": "Serologically distinct forms of H-2Kb are stabilized by loading cells expressing \"empty\" class I major histocompatibility complex (MHC) molecules with different H-2Kb binding peptides. The H-2Kb epitope recognized by monoclonal antibody (mAb) 28.8.6 was stabilized by ovalbumin (OVA) (257-264) and murine cytomegalovirus (MCMV) pp89 (168-176) peptides, but not by vesicular stomatic virus nucleoprotein (VSV NP) (52-59) and influenza NP (Y345-360) peptides. The H-2Kb epitope recognized by mAb 34.4.20 was stabilized by VSV NP (52-59) peptide but not by OVA (257-264), MCMV pp89 (168-176), or influenza NP (Y345-360) peptides. Immunoprecipitation of H-2Kb molecules from normal cells showed that 28.8.6 and 34.4.20 epitopes were only present on a subset of all conformationally reactive H-2Kb molecules. Using alanine-substituted derivatives of the VSV peptide, the 28.8.6 epitope was completely stabilized by substitution of the first residue and partially stabilized by substitution of the third or the fifth residues in the peptides. These results indicate that distinct conformational MHC epitopes are dependent on the specific peptide that occupies the antigenic peptide binding groove on individual MHC molecules. The changes in MHC epitopes observed may also be important in understanding the diversity of T cell receptors used in an immune response and the influence of peptides on development of the T cell repertoire.", "contents": "Major histocompatibility complex conformational epitopes are peptide specific. Serologically distinct forms of H-2Kb are stabilized by loading cells expressing \"empty\" class I major histocompatibility complex (MHC) molecules with different H-2Kb binding peptides. The H-2Kb epitope recognized by monoclonal antibody (mAb) 28.8.6 was stabilized by ovalbumin (OVA) (257-264) and murine cytomegalovirus (MCMV) pp89 (168-176) peptides, but not by vesicular stomatic virus nucleoprotein (VSV NP) (52-59) and influenza NP (Y345-360) peptides. The H-2Kb epitope recognized by mAb 34.4.20 was stabilized by VSV NP (52-59) peptide but not by OVA (257-264), MCMV pp89 (168-176), or influenza NP (Y345-360) peptides. Immunoprecipitation of H-2Kb molecules from normal cells showed that 28.8.6 and 34.4.20 epitopes were only present on a subset of all conformationally reactive H-2Kb molecules. Using alanine-substituted derivatives of the VSV peptide, the 28.8.6 epitope was completely stabilized by substitution of the first residue and partially stabilized by substitution of the third or the fifth residues in the peptides. These results indicate that distinct conformational MHC epitopes are dependent on the specific peptide that occupies the antigenic peptide binding groove on individual MHC molecules. The changes in MHC epitopes observed may also be important in understanding the diversity of T cell receptors used in an immune response and the influence of peptides on development of the T cell repertoire."} {"id": "PMID:1281213", "title": "The Yersinia tyrosine phosphatase: specificity of a bacterial virulence determinant for phosphoproteins in the J774A.1 macrophage.", "content": "YopH is a plasmid-encoded protein tyrosine phosphatase (PTPase) secreted by pathogenic Yersinia. Although the enzyme likely acts to dephosphorylate eukaryotic proteins during Yersinia infection of the mammalian host, the targets of YopH have not been identified. We infected the murine macrophage-like cell line J774A.1 with Yersinia pseudotuberculosis and investigated the specificity of YopH and YopHC403A, a catalytically inactive mutant derivative, for eukaryotic phosphoproteins. Upon infection, YopH specifically and rapidly dephosphorylated a macrophage protein of 120 kD. The 120-kD protein and a previously detected 55-kD substrate of YopH coprecipitated with YopHC403A. Coprecipitation of these proteins required tyrosine phosphorylation and could be competitively inhibited with excess phosphotyrosine. The 120- and 55-kD proteins that coprecipitate with YopHC403A exhibited the in vitro activity of protein tyrosine kinases (PTKases), suggesting that YopH dephosphorylates activated tyrosine kinases in vivo.", "contents": "The Yersinia tyrosine phosphatase: specificity of a bacterial virulence determinant for phosphoproteins in the J774A.1 macrophage. YopH is a plasmid-encoded protein tyrosine phosphatase (PTPase) secreted by pathogenic Yersinia. Although the enzyme likely acts to dephosphorylate eukaryotic proteins during Yersinia infection of the mammalian host, the targets of YopH have not been identified. We infected the murine macrophage-like cell line J774A.1 with Yersinia pseudotuberculosis and investigated the specificity of YopH and YopHC403A, a catalytically inactive mutant derivative, for eukaryotic phosphoproteins. Upon infection, YopH specifically and rapidly dephosphorylated a macrophage protein of 120 kD. The 120-kD protein and a previously detected 55-kD substrate of YopH coprecipitated with YopHC403A. Coprecipitation of these proteins required tyrosine phosphorylation and could be competitively inhibited with excess phosphotyrosine. The 120- and 55-kD proteins that coprecipitate with YopHC403A exhibited the in vitro activity of protein tyrosine kinases (PTKases), suggesting that YopH dephosphorylates activated tyrosine kinases in vivo."} {"id": "PMID:1281214", "title": "Tumor necrosis factor alpha induces adhesion molecule expression on human fetal astrocytes.", "content": "Leukocyte adhesion molecules on endothelial cells of the blood-brain barrier may participate in the entry of leukocytes into the central nervous system. Because astrocytes are also a component of the blood-brain barrier and have been associated with inflammation, we studied the ability of astrocytes to express leukocyte adhesion molecules using Northern blot and immunocytochemical techniques. Astrocytes treated with the proinflammatory cytokine tumor necrosis factor alpha (TNF) expressed messenger RNA for the adhesion molecules E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1, as well as their corresponding proteins. In addition, TNF-treated astrocytes expressed a monocyte adhesion protein identified by our laboratory, recognized by the monoclonal antibody IG9. These results indicate that under inflammatory conditions in the central nervous system, such as multiple sclerosis and acquired immune deficiency syndrome, astrocyte expression of adhesion molecules may facilitate the migration of leukocytes and contribute to the disease process.", "contents": "Tumor necrosis factor alpha induces adhesion molecule expression on human fetal astrocytes. Leukocyte adhesion molecules on endothelial cells of the blood-brain barrier may participate in the entry of leukocytes into the central nervous system. Because astrocytes are also a component of the blood-brain barrier and have been associated with inflammation, we studied the ability of astrocytes to express leukocyte adhesion molecules using Northern blot and immunocytochemical techniques. Astrocytes treated with the proinflammatory cytokine tumor necrosis factor alpha (TNF) expressed messenger RNA for the adhesion molecules E-selectin, vascular cell adhesion molecule 1, and intercellular adhesion molecule 1, as well as their corresponding proteins. In addition, TNF-treated astrocytes expressed a monocyte adhesion protein identified by our laboratory, recognized by the monoclonal antibody IG9. These results indicate that under inflammatory conditions in the central nervous system, such as multiple sclerosis and acquired immune deficiency syndrome, astrocyte expression of adhesion molecules may facilitate the migration of leukocytes and contribute to the disease process."} {"id": "PMID:1281215", "title": "Soluble CD14 participates in the response of cells to lipopolysaccharide.", "content": "CD14 is a 55-kD protein found both as a glycosylphosphatidyl inositol-linked protein on the surface of mononuclear phagocytes and as a soluble protein in the blood. CD14 on the cell membrane (mCD14) has been shown to serve as a receptor for complexes of lipopolysaccharide (LPS) with LPS binding protein, but a function for soluble CD14 (sCD14) has not been described. Here we show that sCD14 enables responses to LPS by cells that do not express CD14. We have examined induction of endothelial-leukocyte adhesion molecule 1 expression by human umbilical vein endothelial cells, interleukin 6 secretion by U373 astrocytoma cells, and cytotoxicity of bovine endothelial cells. None of these cell types express mCD14, yet all respond to LPS in a serum-dependent fashion, and all responses are completely blocked by anti-CD14 antibodies. Immunodepletion of sCD14 from serum prevents responses to LPS, and the responses are restored by addition of sCD14. These studies suggest that a surface anchor is not needed for the function of CD14 and further imply that sCD14 must bind to additional proteins on the cell surface to associate with the cell and transduce a signal. They also indicate that sCD14 may have an important role in potentiating responses to LPS in cells lacking mCD14.", "contents": "Soluble CD14 participates in the response of cells to lipopolysaccharide. CD14 is a 55-kD protein found both as a glycosylphosphatidyl inositol-linked protein on the surface of mononuclear phagocytes and as a soluble protein in the blood. CD14 on the cell membrane (mCD14) has been shown to serve as a receptor for complexes of lipopolysaccharide (LPS) with LPS binding protein, but a function for soluble CD14 (sCD14) has not been described. Here we show that sCD14 enables responses to LPS by cells that do not express CD14. We have examined induction of endothelial-leukocyte adhesion molecule 1 expression by human umbilical vein endothelial cells, interleukin 6 secretion by U373 astrocytoma cells, and cytotoxicity of bovine endothelial cells. None of these cell types express mCD14, yet all respond to LPS in a serum-dependent fashion, and all responses are completely blocked by anti-CD14 antibodies. Immunodepletion of sCD14 from serum prevents responses to LPS, and the responses are restored by addition of sCD14. These studies suggest that a surface anchor is not needed for the function of CD14 and further imply that sCD14 must bind to additional proteins on the cell surface to associate with the cell and transduce a signal. They also indicate that sCD14 may have an important role in potentiating responses to LPS in cells lacking mCD14."} {"id": "PMID:1281216", "title": "Endogenous peptides of a soluble major histocompatibility complex class I molecule, H-2Lds: sequence motif, quantitative binding, and molecular modeling of the complex.", "content": "To gain insight into the rules that govern the binding of endogenous and viral peptides to a given major histocompatibility complex (MHC) class I molecule, we characterized the amino acid sequences of a set of self peptides bound by a soluble analogue of murine H-2Ld, H-2Lds. We tested corresponding synthetic peptides quantitatively for binding in several different assays, and built three-dimensional computer models of eight peptide/H-2Lds complexes, based on the crystallographic structure of the human HLA-B27/peptide complex. Comparison of primary and tertiary structures of bound self and antigenic peptides revealed that residues 2 and 9 were not only restricted in sequence and tolerant of conservative substitutions, but were spatially constrained in the three-dimensional models. The degree of sequence variability of specific residues in MHC-restricted peptides reflected the lack of structural constraint on those amino acids. Thus, amino acid residues that define a peptide motif represent side chains required or preferred for a close fit with the MHC class I heavy chain.", "contents": "Endogenous peptides of a soluble major histocompatibility complex class I molecule, H-2Lds: sequence motif, quantitative binding, and molecular modeling of the complex. To gain insight into the rules that govern the binding of endogenous and viral peptides to a given major histocompatibility complex (MHC) class I molecule, we characterized the amino acid sequences of a set of self peptides bound by a soluble analogue of murine H-2Ld, H-2Lds. We tested corresponding synthetic peptides quantitatively for binding in several different assays, and built three-dimensional computer models of eight peptide/H-2Lds complexes, based on the crystallographic structure of the human HLA-B27/peptide complex. Comparison of primary and tertiary structures of bound self and antigenic peptides revealed that residues 2 and 9 were not only restricted in sequence and tolerant of conservative substitutions, but were spatially constrained in the three-dimensional models. The degree of sequence variability of specific residues in MHC-restricted peptides reflected the lack of structural constraint on those amino acids. Thus, amino acid residues that define a peptide motif represent side chains required or preferred for a close fit with the MHC class I heavy chain."} {"id": "PMID:1281217", "title": "Stimulation of Fc gamma RIIIA results in phospholipase C-gamma 1 tyrosine phosphorylation and p56lck activation.", "content": "Binding of ligand to the alpha subunit of Fc gamma RIIIA(CD16), expressed at the natural killer (NK) cell membrane in association with homo or heterodimers of proteins of the zeta family, results in phosphorylation of several proteins on tyrosine residues. We have analyzed the role of protein tyrosine phosphorylation in the regulation of molecular events induced upon stimulation of Fc gamma RIIIA in NK cells and in T cells expressing the Fc gamma RIII alpha chain in association with endogenous zeta 2 homodimers and devoid of other (CD3, CD2) transducing molecules. Our data indicate that treatment of these cells with protein tyrosine kinase inhibitors prevents not only Fc gamma RIIIA-induced protein tyrosine phosphorylation but also phosphatidylinositol 4,5 diphosphate hydrolysis and increased intracellular Ca2+ concentration, indicating a primary role of tyrosine kinase(s) in the induction of these early activation events. Occupancy of Fc gamma RIIIA by ligand results in phospholipase C (PLC)-gamma 1 tyrosine phosphorylation in NK cells and in Fc gamma RIIIA-transfected CD3-/CD2- T cells, and induces functional activation of p56lck in Fc gamma RIIIA alpha/zeta 2-transfected T cells, suggesting the possibility that the receptor-induced PLC-gamma 1 activation occurs upon phosphorylation of its tyrosine residues mediated by this kinase and is, at least in part, responsible for the signal transduction mediated via CD16 upon ligand binding.", "contents": "Stimulation of Fc gamma RIIIA results in phospholipase C-gamma 1 tyrosine phosphorylation and p56lck activation. Binding of ligand to the alpha subunit of Fc gamma RIIIA(CD16), expressed at the natural killer (NK) cell membrane in association with homo or heterodimers of proteins of the zeta family, results in phosphorylation of several proteins on tyrosine residues. We have analyzed the role of protein tyrosine phosphorylation in the regulation of molecular events induced upon stimulation of Fc gamma RIIIA in NK cells and in T cells expressing the Fc gamma RIII alpha chain in association with endogenous zeta 2 homodimers and devoid of other (CD3, CD2) transducing molecules. Our data indicate that treatment of these cells with protein tyrosine kinase inhibitors prevents not only Fc gamma RIIIA-induced protein tyrosine phosphorylation but also phosphatidylinositol 4,5 diphosphate hydrolysis and increased intracellular Ca2+ concentration, indicating a primary role of tyrosine kinase(s) in the induction of these early activation events. Occupancy of Fc gamma RIIIA by ligand results in phospholipase C (PLC)-gamma 1 tyrosine phosphorylation in NK cells and in Fc gamma RIIIA-transfected CD3-/CD2- T cells, and induces functional activation of p56lck in Fc gamma RIIIA alpha/zeta 2-transfected T cells, suggesting the possibility that the receptor-induced PLC-gamma 1 activation occurs upon phosphorylation of its tyrosine residues mediated by this kinase and is, at least in part, responsible for the signal transduction mediated via CD16 upon ligand binding."} {"id": "PMID:1281218", "title": "Fc gamma receptor activation induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells.", "content": "Crosslinking of the low affinity immunoglobulin G (IgG) Fc receptor (Fc gamma R type III) on natural killer (NK) cells initiates antibody-dependent cellular cytotoxicity. During this process, Fc gamma R stimulation results in the rapid activation of phospholipase C (PLC), which hydrolyzes membrane phosphoinositides, generating inositol-1,4,5-trisphosphate and sn-1,2-diacylglycerol as second messengers. We have recently reported that PLC activation after Fc gamma R stimulation can be inhibited by a protein tyrosine kinase (PTK) inhibitor. Based on the paradigm provided by the receptor tyrosine kinases, we investigated whether PLC-gamma 1 and/or PLC-gamma 2 are expressed in NK cells, and whether the PLC-gamma isoforms are tyrosine phosphorylated in response to Fc gamma R stimulation. Immunoblotting analyses with PLC-gamma 1- and PLC-gamma 2-specific antisera demonstrate that both isoforms are expressed in human NK cells. Furthermore, Fc gamma R crosslinking triggers the tyrosine phosphorylation of both PLC-gamma 1 and PLC-gamma 2 in these cells. Phosphorylation of both isoforms is detectable within 1 min, and returns to basal level within 30 min. Pretreatment with herbimycin A, a PTK inhibitor, blocked the Fc gamma R-induced tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2, and the subsequent release of inositol phosphates. These results suggest that Fc gamma R-initiated phosphoinositide turnover in human NK cells is regulated by the tyrosine phosphorylation of PLC-gamma. More broadly, these observations demonstrate that nonreceptor PTK(s) activated by crosslinkage of a multisubunit receptor can phosphorylate both PLC-gamma isoforms.", "contents": "Fc gamma receptor activation induces the tyrosine phosphorylation of both phospholipase C (PLC)-gamma 1 and PLC-gamma 2 in natural killer cells. Crosslinking of the low affinity immunoglobulin G (IgG) Fc receptor (Fc gamma R type III) on natural killer (NK) cells initiates antibody-dependent cellular cytotoxicity. During this process, Fc gamma R stimulation results in the rapid activation of phospholipase C (PLC), which hydrolyzes membrane phosphoinositides, generating inositol-1,4,5-trisphosphate and sn-1,2-diacylglycerol as second messengers. We have recently reported that PLC activation after Fc gamma R stimulation can be inhibited by a protein tyrosine kinase (PTK) inhibitor. Based on the paradigm provided by the receptor tyrosine kinases, we investigated whether PLC-gamma 1 and/or PLC-gamma 2 are expressed in NK cells, and whether the PLC-gamma isoforms are tyrosine phosphorylated in response to Fc gamma R stimulation. Immunoblotting analyses with PLC-gamma 1- and PLC-gamma 2-specific antisera demonstrate that both isoforms are expressed in human NK cells. Furthermore, Fc gamma R crosslinking triggers the tyrosine phosphorylation of both PLC-gamma 1 and PLC-gamma 2 in these cells. Phosphorylation of both isoforms is detectable within 1 min, and returns to basal level within 30 min. Pretreatment with herbimycin A, a PTK inhibitor, blocked the Fc gamma R-induced tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2, and the subsequent release of inositol phosphates. These results suggest that Fc gamma R-initiated phosphoinositide turnover in human NK cells is regulated by the tyrosine phosphorylation of PLC-gamma. More broadly, these observations demonstrate that nonreceptor PTK(s) activated by crosslinkage of a multisubunit receptor can phosphorylate both PLC-gamma isoforms."} {"id": "PMID:1281219", "title": "Immunoglobulin E plus antigen challenge induces a novel intercrine/chemokine in mouse mast cells.", "content": "In an attempt to characterize genes participating in the allergic late phase reaction, we have isolated a novel intercrine/chemokine (called MARC) from a cDNA library of the stimulated mouse mast cell line, CPII. As measured by Northern blotting, it is strongly upregulated at the mRNA level after the physiological challenge of the cells with immunoglobulin (Ig)E plus antigen. Unstimulated cells completely lack significant, stable expression, as do a number of other, different cell lines (uninduced and induced) and mouse tissues. In contrast to the Northern blot analysis, a polymerase chain reaction (PCR) analysis, performed on CPII cells and on Percoll gradient purified mouse peritoneal mast cells, revealed a basal level of transcription in the uninduced stage. After 2 h of IgE plus antigen challenge, a quantitative reverse transcriptase-PCR, using a spiked in MIMIC, showed a level of transcripts more than 100-fold higher in the CPII cells and 5-20-fold higher in purified mouse peritoneal cavity mast cells. This rapid induction after the Fc epsilon RI challenge, the identification of the gene as a member of the chemokine family, and its upregulated expression in peritoneal mast cells, all suggest an involvement in certain acute and chronic pathological mast cell-driven diseases.", "contents": "Immunoglobulin E plus antigen challenge induces a novel intercrine/chemokine in mouse mast cells. In an attempt to characterize genes participating in the allergic late phase reaction, we have isolated a novel intercrine/chemokine (called MARC) from a cDNA library of the stimulated mouse mast cell line, CPII. As measured by Northern blotting, it is strongly upregulated at the mRNA level after the physiological challenge of the cells with immunoglobulin (Ig)E plus antigen. Unstimulated cells completely lack significant, stable expression, as do a number of other, different cell lines (uninduced and induced) and mouse tissues. In contrast to the Northern blot analysis, a polymerase chain reaction (PCR) analysis, performed on CPII cells and on Percoll gradient purified mouse peritoneal mast cells, revealed a basal level of transcription in the uninduced stage. After 2 h of IgE plus antigen challenge, a quantitative reverse transcriptase-PCR, using a spiked in MIMIC, showed a level of transcripts more than 100-fold higher in the CPII cells and 5-20-fold higher in purified mouse peritoneal cavity mast cells. This rapid induction after the Fc epsilon RI challenge, the identification of the gene as a member of the chemokine family, and its upregulated expression in peritoneal mast cells, all suggest an involvement in certain acute and chronic pathological mast cell-driven diseases."} {"id": "PMID:1281220", "title": "Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents.", "content": "The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel that is regulated by cAMP-dependent phosphorylation and by intracellular ATP. Intracellular ATP also regulates a class of K+ channels that have a distinct pharmacology: they are inhibited by sulfonylureas and activated by a novel class of drugs called K+ channel openers. In search of modulators of CFTR Cl- channels, we examined the effect of sulfonylureas and K+ channel openers on CFTR Cl- currents in cells expressing recombinant CFTR. The sulfonylureas, tolbutamide and glibenclamide, inhibited whole-cell CFTR Cl- currents at half-maximal concentrations of approximately 150 and 20 microM, respectively. Inhibition by both agents showed little voltage dependence and developed slowly; > 90% inhibition occurred 3 min after adding 1 mM tolbutamide or 100 microM glibenclamide. The effect of tolbutamide was reversible, while that of glibenclamide was not. In contrast to their activating effect on K+ channels, the K+ channel openers, diazoxide, BRL 38227, and minoxidil sulfate inhibited CFTR Cl- currents. Half-maximal inhibition was observed at approximately 250 microM diazoxide, 50 microM BRL 38227, and 40 microM minoxidil sulfate. The rank order of potency for inhibition of CFTR Cl- currents was: glibenclamide < BRL 38227 approximately equal to minoxidil sulfate > tolbutamide > diazoxide. Site-directed mutations of CFTR in the first membrane-spanning domain and second nucleotide-binding domain did not affect glibenclamide inhibition of CFTR Cl- currents. However, when part of the R domain was deleted, glibenclamide inhibition showed significant voltage dependence. These agents, especially glibenclamide, which was the most potent, may be of value in identifying CFTR Cl- channels. They or related analogues might also prove to be of value in treating diseases such as diarrhea, which may involve increased activity of the CFTR Cl- channel.", "contents": "Effect of ATP-sensitive K+ channel regulators on cystic fibrosis transmembrane conductance regulator chloride currents. The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl- channel that is regulated by cAMP-dependent phosphorylation and by intracellular ATP. Intracellular ATP also regulates a class of K+ channels that have a distinct pharmacology: they are inhibited by sulfonylureas and activated by a novel class of drugs called K+ channel openers. In search of modulators of CFTR Cl- channels, we examined the effect of sulfonylureas and K+ channel openers on CFTR Cl- currents in cells expressing recombinant CFTR. The sulfonylureas, tolbutamide and glibenclamide, inhibited whole-cell CFTR Cl- currents at half-maximal concentrations of approximately 150 and 20 microM, respectively. Inhibition by both agents showed little voltage dependence and developed slowly; > 90% inhibition occurred 3 min after adding 1 mM tolbutamide or 100 microM glibenclamide. The effect of tolbutamide was reversible, while that of glibenclamide was not. In contrast to their activating effect on K+ channels, the K+ channel openers, diazoxide, BRL 38227, and minoxidil sulfate inhibited CFTR Cl- currents. Half-maximal inhibition was observed at approximately 250 microM diazoxide, 50 microM BRL 38227, and 40 microM minoxidil sulfate. The rank order of potency for inhibition of CFTR Cl- currents was: glibenclamide < BRL 38227 approximately equal to minoxidil sulfate > tolbutamide > diazoxide. Site-directed mutations of CFTR in the first membrane-spanning domain and second nucleotide-binding domain did not affect glibenclamide inhibition of CFTR Cl- currents. However, when part of the R domain was deleted, glibenclamide inhibition showed significant voltage dependence. These agents, especially glibenclamide, which was the most potent, may be of value in identifying CFTR Cl- channels. They or related analogues might also prove to be of value in treating diseases such as diarrhea, which may involve increased activity of the CFTR Cl- channel."} {"id": "PMID:1281221", "title": "Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists.", "content": "Myocardial cells have two types of Ca channels commonly called T-type and L-type. Whole cell Ca channel currents in guinea pig atrial myocytes can be separated and quantitated by analyzing channel closing kinetics after a brief depolarization (tail current analysis). L-type Ca channels deactivate rapidly when the membrane is repolarized and T-type Ca channels deactivate relatively slowly. Ca channel block by the therapeutically useful Ca channel antagonists is voltage dependent, so it is desirable to study block of both channel types over an extended voltage range. Tail current analysis allows this and was used to study block of both types of Ca channels under identical conditions. Amiodarone, bepridil, and cinnarizine block T-type Ca channels more potently than L-type Ca channels when binding equilibrates at normal diastolic potentials (approximately -90 mV). None of these drugs is a selective blocker of T-type Ca channels because block of L-type Ca channels is enhanced when cells are almost completely depolarized. Although weak block of T-type Ca channels by 1,4-dihydropyridines has usually been reported, we found that felodipine blocks these channels with high affinity. When most T-type Ca channels are inactivated, the apparent dissociation constant (KI) is 13 nM. Felodipine also blocks T-type Ca channels in GH3 cells (a cell line derived from rat anterior pituitary), but KI = 700 nM. Thus, T-type Ca channels in different cell types are pharmacologically distinct. Felodipine can block L-type Ca channels in atrial cells more potently than T-type Ca channels, but block of L-type Ca channels is potent only at depolarized potentials; block of both channel types is comparable at normal diastolic membrane potentials. Felodipine and the 1,4-dihydropyridines isradipine and (-)-202-791 are approximately equipotent at blocking T-type Ca channels, but differ substantially in potency for block of L-type Ca channels. Block of T-type Ca channels may account for some of the pharmacological effects of 1,4-dihydropyridines and for the antiarrhythmic activity of amiodarone and bepridil.", "contents": "Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. Myocardial cells have two types of Ca channels commonly called T-type and L-type. Whole cell Ca channel currents in guinea pig atrial myocytes can be separated and quantitated by analyzing channel closing kinetics after a brief depolarization (tail current analysis). L-type Ca channels deactivate rapidly when the membrane is repolarized and T-type Ca channels deactivate relatively slowly. Ca channel block by the therapeutically useful Ca channel antagonists is voltage dependent, so it is desirable to study block of both channel types over an extended voltage range. Tail current analysis allows this and was used to study block of both types of Ca channels under identical conditions. Amiodarone, bepridil, and cinnarizine block T-type Ca channels more potently than L-type Ca channels when binding equilibrates at normal diastolic potentials (approximately -90 mV). None of these drugs is a selective blocker of T-type Ca channels because block of L-type Ca channels is enhanced when cells are almost completely depolarized. Although weak block of T-type Ca channels by 1,4-dihydropyridines has usually been reported, we found that felodipine blocks these channels with high affinity. When most T-type Ca channels are inactivated, the apparent dissociation constant (KI) is 13 nM. Felodipine also blocks T-type Ca channels in GH3 cells (a cell line derived from rat anterior pituitary), but KI = 700 nM. Thus, T-type Ca channels in different cell types are pharmacologically distinct. Felodipine can block L-type Ca channels in atrial cells more potently than T-type Ca channels, but block of L-type Ca channels is potent only at depolarized potentials; block of both channel types is comparable at normal diastolic membrane potentials. Felodipine and the 1,4-dihydropyridines isradipine and (-)-202-791 are approximately equipotent at blocking T-type Ca channels, but differ substantially in potency for block of L-type Ca channels. Block of T-type Ca channels may account for some of the pharmacological effects of 1,4-dihydropyridines and for the antiarrhythmic activity of amiodarone and bepridil."} {"id": "PMID:1281222", "title": "Influence of spinal cord transection on the presence and axonal transport of CGRP-, chromogranin A-, VIP-, synapsin I-, and synaptophysin-like immunoreactivities in rat motor nerve.", "content": "Using immunofluorescence and cytofluorimetric scanning (CFS), we investigated the short-term (1-7 days) influence of lower thoracic spinal cord transection on lumbar motor neurons. The content of calcitonin gene-related peptide- (CGRP) like immunoreactivity (LI), chromogranin A (Chr A)-LI, vasoactive intestinal polypeptide (VIP)-LI, Syn I-LI, and synaptophysin (p38)-LI in motor perikarya, and the anterograde and retrograde axonal transport of these substances in the sciatic nerve, were studied in nerve crush (6 h) experiments. During the week after transection, CGRP-LI in perikarya decreased, whereas Chr A-LI increased. VIP-LI, co-localized with Chr A-LI in motor perikarya, did not change after transection. The antero- and retrograde transport of CGRP-LI in the sciatic nerve, occurring in both motor and sensory axons, appeared unchanged in cytofluorimetric scanning (CFS) graphs, but the microscopical picture clearly showed that large motor axons had a decreased content of CGRP-LI at 3 and 7 days posttransection, whereas thinner axons were unchanged in fluorescence intensity. The anterograde transport of Chr A-LI, present in both motor and postganglionic adrenergic axons, was decreased 1 and 3 days after lesion, but returned to control by day 7. There was a marked decrease in anterograde transport of VIP-LI, present mainly in postganglionic sympathetic axons, at day 3, but at 7 days transport was normal. The amounts of transported p38, the synaptic vesicle marker, were in the normal range during the whole period. Syn I-LI accumulation anterogradely was somewhat decreased at 3 and 7 days posttransection, and at 1 day the retrograde accumulation was significantly increased. The results suggest that removal of supraspinal input to intact lower motor neurons causes alterations in metabolism and axonal transport of organelle-associated substances, partly probably related to the complex pattern of transmitter leakage from degenerating, descending nerve terminals. These alterations appear to take place also in postganglionic sympathetic neurons in the sciatic nerve, that originate in the lumbar sympathetic chain.", "contents": "Influence of spinal cord transection on the presence and axonal transport of CGRP-, chromogranin A-, VIP-, synapsin I-, and synaptophysin-like immunoreactivities in rat motor nerve. Using immunofluorescence and cytofluorimetric scanning (CFS), we investigated the short-term (1-7 days) influence of lower thoracic spinal cord transection on lumbar motor neurons. The content of calcitonin gene-related peptide- (CGRP) like immunoreactivity (LI), chromogranin A (Chr A)-LI, vasoactive intestinal polypeptide (VIP)-LI, Syn I-LI, and synaptophysin (p38)-LI in motor perikarya, and the anterograde and retrograde axonal transport of these substances in the sciatic nerve, were studied in nerve crush (6 h) experiments. During the week after transection, CGRP-LI in perikarya decreased, whereas Chr A-LI increased. VIP-LI, co-localized with Chr A-LI in motor perikarya, did not change after transection. The antero- and retrograde transport of CGRP-LI in the sciatic nerve, occurring in both motor and sensory axons, appeared unchanged in cytofluorimetric scanning (CFS) graphs, but the microscopical picture clearly showed that large motor axons had a decreased content of CGRP-LI at 3 and 7 days posttransection, whereas thinner axons were unchanged in fluorescence intensity. The anterograde transport of Chr A-LI, present in both motor and postganglionic adrenergic axons, was decreased 1 and 3 days after lesion, but returned to control by day 7. There was a marked decrease in anterograde transport of VIP-LI, present mainly in postganglionic sympathetic axons, at day 3, but at 7 days transport was normal. The amounts of transported p38, the synaptic vesicle marker, were in the normal range during the whole period. Syn I-LI accumulation anterogradely was somewhat decreased at 3 and 7 days posttransection, and at 1 day the retrograde accumulation was significantly increased. The results suggest that removal of supraspinal input to intact lower motor neurons causes alterations in metabolism and axonal transport of organelle-associated substances, partly probably related to the complex pattern of transmitter leakage from degenerating, descending nerve terminals. These alterations appear to take place also in postganglionic sympathetic neurons in the sciatic nerve, that originate in the lumbar sympathetic chain."} {"id": "PMID:1281223", "title": "Validation of a new quality of life questionnaire for benign prostatic hyperplasia.", "content": "In planning a longitudinal study to characterize the natural history of benign prostatic hyperplasia (BPH), we validated a new disease-specific quality of life questionnaire in a pilot study. We studied 110 men in Rochester, Minnesota who spanned the severity of BPH, from men with no known BPH to men who underwent surgery for this condition. Baseline data were obtained on all men, and the 30 who underwent prostatectomy were re-interviewed to test responsiveness. Reproducibility was examined on the pre-post responses (10 weeks apart) of the 37 men with BPH who did not undergo prostatectomy. Six of twelve question domains were retained in the final questionnaire on the basis of their responsiveness to change, reproducibility, internal consistency, and validity. These were: urinary symptoms, degree of bother due to urinary symptoms, BPH-specific interference with activities, general psychological well-being, worries and concerns, and sexual satisfaction. Most of the more generic measures were deleted.", "contents": "Validation of a new quality of life questionnaire for benign prostatic hyperplasia. In planning a longitudinal study to characterize the natural history of benign prostatic hyperplasia (BPH), we validated a new disease-specific quality of life questionnaire in a pilot study. We studied 110 men in Rochester, Minnesota who spanned the severity of BPH, from men with no known BPH to men who underwent surgery for this condition. Baseline data were obtained on all men, and the 30 who underwent prostatectomy were re-interviewed to test responsiveness. Reproducibility was examined on the pre-post responses (10 weeks apart) of the 37 men with BPH who did not undergo prostatectomy. Six of twelve question domains were retained in the final questionnaire on the basis of their responsiveness to change, reproducibility, internal consistency, and validity. These were: urinary symptoms, degree of bother due to urinary symptoms, BPH-specific interference with activities, general psychological well-being, worries and concerns, and sexual satisfaction. Most of the more generic measures were deleted."} {"id": "PMID:1281224", "title": "Intracerebral chemotherapy in the 9L rat brain tumor model.", "content": "We have used the 9L rat brain tumor model to search for effective chemotherapeutic approaches to the management of brain tumors. Several antineoplastic agents which have been proposed or are currently being used for human brain tumors, including 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), bleomycin, aziridinylbenzoquinone (AZQ), cis-Platinum, and acivicin, were administered intravenously (iv), intraperitoneally (ip), or intracerebrally (ic) to rats burdened with the intracranial 9L gliosarcoma. The results confirm that BCNU is the most effective systemic agent among the chemotherapeutic agents tested as indicated by its ability to significantly increase the median survival time (MST) and life span of the tumor-burdened animals. Bleomycin is an effective agent against the intracranial 9L tumor when administered ic. While neither systemic single iv dose AZQ (0.5-2.5 mg/kg) nor multiple ip treatments (0.5-1.0 mg/kg x 5, q 6 h) were effective in prolonging the survival, single ic dose AZQ (5-50 micrograms/rat) treatment significantly increased the MST of the treated animals (P < 0.05). Systemic AZQ treatments using higher doses produced a hematological toxicity, resulting in a decrease in MST of the treated animals. Cis-Platinum, either administered ip or ic, produced only a marginal effect on survival, although acute neurologic toxicity limited the dose of cis-Platinum that could be administered ic. Acivicin, either administered ip or ic, produced no effect on the survival of treated animals. Our results suggest that local treatment with certain antineoplastic agents may be an efficient therapy in the management of brain tumors.", "contents": "Intracerebral chemotherapy in the 9L rat brain tumor model. We have used the 9L rat brain tumor model to search for effective chemotherapeutic approaches to the management of brain tumors. Several antineoplastic agents which have been proposed or are currently being used for human brain tumors, including 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU), bleomycin, aziridinylbenzoquinone (AZQ), cis-Platinum, and acivicin, were administered intravenously (iv), intraperitoneally (ip), or intracerebrally (ic) to rats burdened with the intracranial 9L gliosarcoma. The results confirm that BCNU is the most effective systemic agent among the chemotherapeutic agents tested as indicated by its ability to significantly increase the median survival time (MST) and life span of the tumor-burdened animals. Bleomycin is an effective agent against the intracranial 9L tumor when administered ic. While neither systemic single iv dose AZQ (0.5-2.5 mg/kg) nor multiple ip treatments (0.5-1.0 mg/kg x 5, q 6 h) were effective in prolonging the survival, single ic dose AZQ (5-50 micrograms/rat) treatment significantly increased the MST of the treated animals (P < 0.05). Systemic AZQ treatments using higher doses produced a hematological toxicity, resulting in a decrease in MST of the treated animals. Cis-Platinum, either administered ip or ic, produced only a marginal effect on survival, although acute neurologic toxicity limited the dose of cis-Platinum that could be administered ic. Acivicin, either administered ip or ic, produced no effect on the survival of treated animals. Our results suggest that local treatment with certain antineoplastic agents may be an efficient therapy in the management of brain tumors."} {"id": "PMID:1281225", "title": "Effects of EGF-dextran-tyrosine-131I conjugates on the clonogenic survival of cultured glioma cells.", "content": "Epidermal growth factor, EGF, and 131I or 125I-labelled tyrosine were conjugated to the sugar polymer dextran. The conjugates bound to EGF-receptor rich human glioma cells in culture and the binding was mainly receptor specific because cells presaturated with nonradioactive EGF gave strongly reduced binding. The 131I labelled conjugates were used in tests on cellular retention and therapeutical effects. 131I activity delivered to the cells as EGF-dextran-tyrosine-131I remained cell-associated for much longer periods of time than 131I activity delivered by only EGF. The amount of cell-associated 131I activity was nearly constant for up to 25 hours. The 131I labelled conjugate gave, after a one hour incubation period for binding followed by a 25 hour incubation in nonradioactive medium, a good therapeutical effect. This effect, which corresponded to about 3.0 Gy of external 60Co radiation, was due to the specifically bound 131I. The comparatively small effects of nonbound 131I in the culture medium, present only during the first incubation hour, were measured in control experiments with presaturated receptors and were corrected for in the evaluation of the EGF-receptor mediated effects. Control experiments showed that neither nonradioactive EGF nor non-radioactive EGF-dextran conjugates gave measurable effects on clonogenic growth. The results obtained were promising and the possibilities to use EGF-dextran conjugates for therapy should be further examined.", "contents": "Effects of EGF-dextran-tyrosine-131I conjugates on the clonogenic survival of cultured glioma cells. Epidermal growth factor, EGF, and 131I or 125I-labelled tyrosine were conjugated to the sugar polymer dextran. The conjugates bound to EGF-receptor rich human glioma cells in culture and the binding was mainly receptor specific because cells presaturated with nonradioactive EGF gave strongly reduced binding. The 131I labelled conjugates were used in tests on cellular retention and therapeutical effects. 131I activity delivered to the cells as EGF-dextran-tyrosine-131I remained cell-associated for much longer periods of time than 131I activity delivered by only EGF. The amount of cell-associated 131I activity was nearly constant for up to 25 hours. The 131I labelled conjugate gave, after a one hour incubation period for binding followed by a 25 hour incubation in nonradioactive medium, a good therapeutical effect. This effect, which corresponded to about 3.0 Gy of external 60Co radiation, was due to the specifically bound 131I. The comparatively small effects of nonbound 131I in the culture medium, present only during the first incubation hour, were measured in control experiments with presaturated receptors and were corrected for in the evaluation of the EGF-receptor mediated effects. Control experiments showed that neither nonradioactive EGF nor non-radioactive EGF-dextran conjugates gave measurable effects on clonogenic growth. The results obtained were promising and the possibilities to use EGF-dextran conjugates for therapy should be further examined."} {"id": "PMID:1281226", "title": "Evaluation of blood-brain barrier permeability and the effect of interferon in mouse glioma model.", "content": "The aim of this study was to evaluate whether interferon [IFN] can affect intracerebrally grown glioma and how alteration of the blood-brain barrier [BBB] may influence this effect. An intracerebrally implanted glioma G-26 (G-26) mouse brain-tumor model was developed and used in these studies. Histological characterization of this intracerebrally grown tumor revealed its anaplastic character. The astrocytic origin of G-26 was evidenced by glial fibrillary acidic protein staining and electron microscopic visualization of glial filaments. A study of tumor progression and animal survival showed development of a well defined tumor nodule within approximately seven days after the implantation. The median animal survival time was 27 +/- 3.8 days. The integrity of the blood-brain barrier [BBB] within the tumor was evaluated by the intravenous injection of horseradish peroxidase at days 3, 7, 10 and 20 after brain tumor implant and compared to 'sham' controls. The tumor-induced BBB alteration was progressive from day 3 to day 20. Glioma-26 subcutaneously passed in C57BL/6 mice was also continuously cultured in vitro. Its proliferation was inhibited by homologous mouse interferon alpha/beta [MuIFN alpha/beta] but not by human interferon alpha lymphoblastoid or human interferon beta. The in vivo studies of G-26 glioma treatment with MuIFN alpha/beta were performed using single bolus of IFN in osmotically altered animals or slow IFN infusion through osmotic micro-pumps. The slow infusion of IFN had no effect on animal survival. However, a statistically significant increase in animal survival was observed after single bolus IFN treatment following osmotic BBB alteration.", "contents": "Evaluation of blood-brain barrier permeability and the effect of interferon in mouse glioma model. The aim of this study was to evaluate whether interferon [IFN] can affect intracerebrally grown glioma and how alteration of the blood-brain barrier [BBB] may influence this effect. An intracerebrally implanted glioma G-26 (G-26) mouse brain-tumor model was developed and used in these studies. Histological characterization of this intracerebrally grown tumor revealed its anaplastic character. The astrocytic origin of G-26 was evidenced by glial fibrillary acidic protein staining and electron microscopic visualization of glial filaments. A study of tumor progression and animal survival showed development of a well defined tumor nodule within approximately seven days after the implantation. The median animal survival time was 27 +/- 3.8 days. The integrity of the blood-brain barrier [BBB] within the tumor was evaluated by the intravenous injection of horseradish peroxidase at days 3, 7, 10 and 20 after brain tumor implant and compared to 'sham' controls. The tumor-induced BBB alteration was progressive from day 3 to day 20. Glioma-26 subcutaneously passed in C57BL/6 mice was also continuously cultured in vitro. Its proliferation was inhibited by homologous mouse interferon alpha/beta [MuIFN alpha/beta] but not by human interferon alpha lymphoblastoid or human interferon beta. The in vivo studies of G-26 glioma treatment with MuIFN alpha/beta were performed using single bolus of IFN in osmotically altered animals or slow IFN infusion through osmotic micro-pumps. The slow infusion of IFN had no effect on animal survival. However, a statistically significant increase in animal survival was observed after single bolus IFN treatment following osmotic BBB alteration."} {"id": "PMID:1281228", "title": "Changes in cytokeratin expression during the development of the human oral mucosa.", "content": "The changes in cytokeratin expression by the developing oral mucosa of 10 to 23-week-old human fetuses were studied by indirect immunofluorescence using a panel of 15 monoclonal antibodies. The lining and masticatory mucosae were incompletely differentiated in 10-wk fetuses, since they expressed identical patterns of cytokeratins (CK 4, 5, 8, 13, 18, 19 and probably CK 14, 16, 17) very similar to that of adult alveolar mucosa. The main difference was the presence of cytokeratins 8, 18 and 19 in embryonic tissues. Cytokeratins 1, 2, 10 and 11 began to appear in gingival and hard palate epithelium from wk 11, predicting the differentiation of the masticatory mucosa by wk 16. The patterns of cytokeratin expression in the 23-wk fetus in the lining and masticatory mucosae appear to be different. In lining mucosa, the only difference from the 10th wk is a decrease in cytokeratins 8, 18 and 19, whereas the pattern of cytokeratin expression in masticatory mucosa (CK 1, 2, 4, 5, 8, 10, 11, 13, 18, 19 and probably CK 14, 16 and 17) is now very near that of adult gingiva. This pattern appears, as in the adult, to be similar to that of the epidermis in the same period.", "contents": "Changes in cytokeratin expression during the development of the human oral mucosa. The changes in cytokeratin expression by the developing oral mucosa of 10 to 23-week-old human fetuses were studied by indirect immunofluorescence using a panel of 15 monoclonal antibodies. The lining and masticatory mucosae were incompletely differentiated in 10-wk fetuses, since they expressed identical patterns of cytokeratins (CK 4, 5, 8, 13, 18, 19 and probably CK 14, 16, 17) very similar to that of adult alveolar mucosa. The main difference was the presence of cytokeratins 8, 18 and 19 in embryonic tissues. Cytokeratins 1, 2, 10 and 11 began to appear in gingival and hard palate epithelium from wk 11, predicting the differentiation of the masticatory mucosa by wk 16. The patterns of cytokeratin expression in the 23-wk fetus in the lining and masticatory mucosae appear to be different. In lining mucosa, the only difference from the 10th wk is a decrease in cytokeratins 8, 18 and 19, whereas the pattern of cytokeratin expression in masticatory mucosa (CK 1, 2, 4, 5, 8, 10, 11, 13, 18, 19 and probably CK 14, 16 and 17) is now very near that of adult gingiva. This pattern appears, as in the adult, to be similar to that of the epidermis in the same period."} {"id": "PMID:1281229", "title": "Vascular reaction in plaque-induced gingivitis: a quantitative approach.", "content": "The clinical diagnostic features of gingivitis such as redness, swelling and bleeding are based on vascular changes. It would be desirable to directly make use of the vascular changes in the clinical evaluation of gingival inflammation. In the present study, capillary microscopy was used for quantitative evaluation of the vascular reaction of the marginal gingiva in response to experimental plaque formation in 6 healthy students. Low power stereomicroscopy was used and the number of vessel endings was evaluated from stereophotographs. A gradual increase in the number of visible vessel endings was observed over time of plaque accumulation. The mean +/- SEM at baseline was 24.0 +/- 6.30 as compared to 77.0 +/- 10.02 at day 28. After removal of plaque and re-institution of oral hygiene measures, a return toward pre-experimental numbers was observed. Throughout the test the number of vessel endings within the proximal-papillary part of the marginal gingiva was less than that within the basal-labial part. The results indicate that low power stereophotomicroscopy is a useful tool for the clinical study of inflammatory changes in the gingival vasculature.", "contents": "Vascular reaction in plaque-induced gingivitis: a quantitative approach. The clinical diagnostic features of gingivitis such as redness, swelling and bleeding are based on vascular changes. It would be desirable to directly make use of the vascular changes in the clinical evaluation of gingival inflammation. In the present study, capillary microscopy was used for quantitative evaluation of the vascular reaction of the marginal gingiva in response to experimental plaque formation in 6 healthy students. Low power stereomicroscopy was used and the number of vessel endings was evaluated from stereophotographs. A gradual increase in the number of visible vessel endings was observed over time of plaque accumulation. The mean +/- SEM at baseline was 24.0 +/- 6.30 as compared to 77.0 +/- 10.02 at day 28. After removal of plaque and re-institution of oral hygiene measures, a return toward pre-experimental numbers was observed. Throughout the test the number of vessel endings within the proximal-papillary part of the marginal gingiva was less than that within the basal-labial part. The results indicate that low power stereophotomicroscopy is a useful tool for the clinical study of inflammatory changes in the gingival vasculature."} {"id": "PMID:1281230", "title": "Endothelial cell leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression in gingival tissue during health and experimentally-induced gingivitis.", "content": "The changes in vascular adhesion molecule expression and numbers of infiltrating leukocytes during a 21-day experimental gingivitis episode were investigated immunohistochemically. Monoclonal antibodies to ELAM-1 (1.2B6), ICAM-1 (6.5B5), CD3 (OKT3-pan-T cell) and neutrophils (PMN-elastase) were used to identify positive vessels and leukocytes within gingival biopsies taken on d 0, 7, 14 and 21. Vascular endothelium expressed ELAM-1 and ICAM-1 both in clinically 'healthy' tissue (d 0) and in experimentally inflamed tissue (d 7 to 21). Positive vessels were found mainly in the connective tissue subjacent to the junctional epithelium where the highest numbers of T cells and neutrophils were also seen. Although T cells were found in all tissue areas studied, neutrophils were largely concentrated in the junctional epithelium and the subjacent connective tissue but were absent from the oral epithelial region. As the experimental gingivitis developed, the number of T cells or neutrophils in the different tissue regions did not change significantly although the most intense vascular ICAM-1 and ELAM-1 staining redistributed to the CT adjacent to the junctional epithelium. A prominent feature was the intense ICAM-1 positive staining of the junctional epithelium and its absence in the closely adjacent oral epithelium, in both clinically 'healthy' and inflamed tissue. The gradient of ICAM-1 in junctional epithelium, with the strongest staining on the crevicular aspect plus the vascular expression of ELAM-1 and ICAM-1 in both clinically 'healthy' and inflamed tissue may be crucial processes which direct leukocyte migration towards the gingival crevice.", "contents": "Endothelial cell leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression in gingival tissue during health and experimentally-induced gingivitis. The changes in vascular adhesion molecule expression and numbers of infiltrating leukocytes during a 21-day experimental gingivitis episode were investigated immunohistochemically. Monoclonal antibodies to ELAM-1 (1.2B6), ICAM-1 (6.5B5), CD3 (OKT3-pan-T cell) and neutrophils (PMN-elastase) were used to identify positive vessels and leukocytes within gingival biopsies taken on d 0, 7, 14 and 21. Vascular endothelium expressed ELAM-1 and ICAM-1 both in clinically 'healthy' tissue (d 0) and in experimentally inflamed tissue (d 7 to 21). Positive vessels were found mainly in the connective tissue subjacent to the junctional epithelium where the highest numbers of T cells and neutrophils were also seen. Although T cells were found in all tissue areas studied, neutrophils were largely concentrated in the junctional epithelium and the subjacent connective tissue but were absent from the oral epithelial region. As the experimental gingivitis developed, the number of T cells or neutrophils in the different tissue regions did not change significantly although the most intense vascular ICAM-1 and ELAM-1 staining redistributed to the CT adjacent to the junctional epithelium. A prominent feature was the intense ICAM-1 positive staining of the junctional epithelium and its absence in the closely adjacent oral epithelium, in both clinically 'healthy' and inflamed tissue. The gradient of ICAM-1 in junctional epithelium, with the strongest staining on the crevicular aspect plus the vascular expression of ELAM-1 and ICAM-1 in both clinically 'healthy' and inflamed tissue may be crucial processes which direct leukocyte migration towards the gingival crevice."} {"id": "PMID:1281231", "title": "Production of polyclonal antibody to the bovine adrenal atrial natriuretic factor-R1 receptor.", "content": "A polyclonal antibody monospecific for an intracellular epitope of the atrial natriuretic factor (ANF)-R1 receptor was produced. The receptor protein (200 pmoles) was purified to homogeneity from bovine adrenal zona glomerulosa (BAZG), reduced, alkylated and digested with trypsin. The tryptic fragments were purified by reverse-phase h.p.l.c. on a C18 column. Based on the sequence of one of these fragments, a peptide was chemically synthesized, coupled to thyroglobulin and injected into rabbits. The antibody obtained was shown to be specific for the R1-type as no receptor was detected in bovine red blood cells (RBC) (which are devoid of ANF receptors) and in NIH-3T3 cell membranes (where only the R2-type is expressed). Several other tissues were screened and comparison of the immunoreactive receptor density estimates with those obtained by ANF binding yielded a correlation coefficient (r2) of 0.965. The minimal detectable dose was typically 3 fmoles/tube and the ED50 of the RIA was 30 fmoles/tube. Cyanogen bromide digestion of the receptor was essential for antigenic detection, indicating that the epitope is probably hindered due to the tertiary structure of the native protein. Moreover, location of the epitope in the kinase homology domain of the receptor, combined with partial tryptic digestion, suggests that the proteolysis-sensitive region of the receptor is located between the transmembrane-spanning domain and the amino acid 586. This method of production of antibodies should be useful to precisely map the amino acids involved in various functions of the receptor.", "contents": "Production of polyclonal antibody to the bovine adrenal atrial natriuretic factor-R1 receptor. A polyclonal antibody monospecific for an intracellular epitope of the atrial natriuretic factor (ANF)-R1 receptor was produced. The receptor protein (200 pmoles) was purified to homogeneity from bovine adrenal zona glomerulosa (BAZG), reduced, alkylated and digested with trypsin. The tryptic fragments were purified by reverse-phase h.p.l.c. on a C18 column. Based on the sequence of one of these fragments, a peptide was chemically synthesized, coupled to thyroglobulin and injected into rabbits. The antibody obtained was shown to be specific for the R1-type as no receptor was detected in bovine red blood cells (RBC) (which are devoid of ANF receptors) and in NIH-3T3 cell membranes (where only the R2-type is expressed). Several other tissues were screened and comparison of the immunoreactive receptor density estimates with those obtained by ANF binding yielded a correlation coefficient (r2) of 0.965. The minimal detectable dose was typically 3 fmoles/tube and the ED50 of the RIA was 30 fmoles/tube. Cyanogen bromide digestion of the receptor was essential for antigenic detection, indicating that the epitope is probably hindered due to the tertiary structure of the native protein. Moreover, location of the epitope in the kinase homology domain of the receptor, combined with partial tryptic digestion, suggests that the proteolysis-sensitive region of the receptor is located between the transmembrane-spanning domain and the amino acid 586. This method of production of antibodies should be useful to precisely map the amino acids involved in various functions of the receptor."} {"id": "PMID:1281232", "title": "Is the endoscopic view too narrow?", "content": "Palliative laser therapy for gastrointestinal tumors is now well established. Its use however may be associated with complications not directly attributable to the laser therapy. These complications potentially decrease the quality of life which opposes the aim of treatment.", "contents": "Is the endoscopic view too narrow? Palliative laser therapy for gastrointestinal tumors is now well established. Its use however may be associated with complications not directly attributable to the laser therapy. These complications potentially decrease the quality of life which opposes the aim of treatment."} {"id": "PMID:1281233", "title": "Use of ribosomal RNA gene restriction patterns to investigate two outbreaks of Campylobacter enteritis in Melbourne, Australia.", "content": "The analysis of ribosomal RNA (rRNA) gene patterns (ribotyping) has been used to differentiate strains within bacterial species. We used this method to investigate two outbreaks of campylobacter enteritis that occurred recently in Melbourne, Australia. The first outbreak involved seven patients although isolates from only five patients were available for typing. The second outbreak consisted of three patients infected with human immunodeficiency virus (HIV) on the same ward of a hospital. Analysis of the rRNA gene patterns revealed identical patterns for the isolates from five patients in the first outbreak, suggesting that these isolates were from the same source. However, ribotyping of the four isolates from the second outbreak showed three distinct ribotypes indicative of contact with unrelated sources. This study demonstrated that ribotyping is a useful, reliable and convenient typing scheme for epidemiological purposes.", "contents": "Use of ribosomal RNA gene restriction patterns to investigate two outbreaks of Campylobacter enteritis in Melbourne, Australia. The analysis of ribosomal RNA (rRNA) gene patterns (ribotyping) has been used to differentiate strains within bacterial species. We used this method to investigate two outbreaks of campylobacter enteritis that occurred recently in Melbourne, Australia. The first outbreak involved seven patients although isolates from only five patients were available for typing. The second outbreak consisted of three patients infected with human immunodeficiency virus (HIV) on the same ward of a hospital. Analysis of the rRNA gene patterns revealed identical patterns for the isolates from five patients in the first outbreak, suggesting that these isolates were from the same source. However, ribotyping of the four isolates from the second outbreak showed three distinct ribotypes indicative of contact with unrelated sources. This study demonstrated that ribotyping is a useful, reliable and convenient typing scheme for epidemiological purposes."} {"id": "PMID:1281234", "title": "Identification of highly conserved and species-specific polypeptides of Haemophilus ducreyi.", "content": "Chancroid is a sexually transmitted diseased caused by Haemophilus ducreyi. The pathological manifestations of chancroid are unique among Haemophilus species and the virulence factors of H. ducreyi that account for these features have not been identified. Some of these virulence factors may be unique components of H. ducreyi, but attempts to identify H. ducreyi-specific components have been unsuccessful. Four polypeptides--A, B, C and D of 83, 77, 56 and 28 kDa, respectively--were identified with a panel of nine H. ducreyi-specific monoclonal antibodies (MAbs). Polypeptide C was one of the five major proteins in H. ducreyi and demonstrated micro-heterogeneity in SDS-PAGE. Polypeptides A, B and D were present in only small amounts in whole-cell lysates of H. ducreyi. The relative amounts of A and B varied, suggesting that they may be precursor molecules. The unique polypeptides C and D were not exposed on the surface. Polypeptide C was highly soluble and did not appear to be membrane-bound, whereas polypeptide D appeared to partition with the cytoplasmic membrane and was soluble in Sarkosyl. All four polypeptides appeared to be unique to H. ducreyi since MAbs directed against them did not cross-react with H. influenzae, H. parainfluenzae or Neisseria gonorrhoeae. The mol. wts of all of these polypeptides were conserved throughout 35 clinical isolates collected from 15 cities in eight countries and one reference strain of H. ducreyi that were tested.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Identification of highly conserved and species-specific polypeptides of Haemophilus ducreyi. Chancroid is a sexually transmitted diseased caused by Haemophilus ducreyi. The pathological manifestations of chancroid are unique among Haemophilus species and the virulence factors of H. ducreyi that account for these features have not been identified. Some of these virulence factors may be unique components of H. ducreyi, but attempts to identify H. ducreyi-specific components have been unsuccessful. Four polypeptides--A, B, C and D of 83, 77, 56 and 28 kDa, respectively--were identified with a panel of nine H. ducreyi-specific monoclonal antibodies (MAbs). Polypeptide C was one of the five major proteins in H. ducreyi and demonstrated micro-heterogeneity in SDS-PAGE. Polypeptides A, B and D were present in only small amounts in whole-cell lysates of H. ducreyi. The relative amounts of A and B varied, suggesting that they may be precursor molecules. The unique polypeptides C and D were not exposed on the surface. Polypeptide C was highly soluble and did not appear to be membrane-bound, whereas polypeptide D appeared to partition with the cytoplasmic membrane and was soluble in Sarkosyl. All four polypeptides appeared to be unique to H. ducreyi since MAbs directed against them did not cross-react with H. influenzae, H. parainfluenzae or Neisseria gonorrhoeae. The mol. wts of all of these polypeptides were conserved throughout 35 clinical isolates collected from 15 cities in eight countries and one reference strain of H. ducreyi that were tested.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281237", "title": "Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.", "content": "Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy.", "contents": "Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma. Axillary lymph node status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Our recent findings indicated that microvessel density (count or grade) in invasive breast carcinoma (a measure of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. This study was designed to further define the relationship of microvessel density with overall and relapse-free survival and with other reported prognostic indicators in breast carcinoma. In a prospective, blinded study of 165 consecutive patients, the microvessels within primary invasive breast carcinoma were highlighted by immunocytochemical staining to detect factor VIII-related antigen. Using light microscopy, we counted microvessels per 200x field in the most active areas of neovascularization and graded microvessel density. These findings were correlated, by univariate and multivariate analyses, with overall and relapse-free survival, axillary node status, and other prognostic indicators (median follow-up, 51 months). There was a highly significant (P < or = .001) association of microvessel density with overall survival and relapse-free survival in all patients, including node-negative and node-positive subsets. All patients with breast carcinomas having more than 100 microvessels per 200x field experienced tumor recurrence within 33 months of diagnosis, compared with less than 5% of the patients with breast carcinoma having 33 or fewer microvessels per 200x field. Moreover, microvessel density was the only statistically significant predictor of overall survival among node-negative women (P < .001). Only microvessel density (P < .001) and histologic grade (P = .04) showed statistically significant correlations with relapse-free survival in the node-negative subset. Microvessel density in the area of the most intense neovascularization in invasive breast carcinoma is an independent and highly significant prognostic indicator for overall and relapse-free survival in patients with early-stage breast carcinoma (I or II by International Union Against Cancer criteria). Such an indicator would be useful in selection of those node-negative patients with breast carcinoma who are at high risk for having occult metastasis at presentation. These patients could then be given systemic adjuvant therapy."} {"id": "PMID:1281239", "title": "Serodiagnosis of hepatitis C in acute and chronic liver disease in southwestern Saudi Arabia.", "content": "The extent of involvement of hepatitis C, as compared to hepatitis A and hepatitis B, virus infection in acute and chronic liver disease in the Asir Region, southwestern Saudi Arabia, was assessed in 898 patients hospitalized during the period from June 1990 to November 1991. Acute icteric hepatitis cases with severe onset were distinguished by their referral to the fever hospital while cases with milder onset and those with chronic hepatitis were followed at two general hospitals. Antibodies to the c-100-3 antigen of hepatitis C virus (anti HCV) were detected in a significant proportion of patients with chronic liver disease (chronic active hepatitis (65%), cirrhosis (44%)). Anti HCV was also detected in patients with acute hepatitis with milder onset at the general hospitals (10.9%) but proportionately much less in patients at the fever referral hospital (< 1%) where hepatitis A (52%) and, to a lesser extent hepatitis B (11%), were mostly diagnosed. These results indicate that HCV is a major identifiable infection in hospitalized patients with chronic liver disease in this region but that anti HCV antibodies (c-100-3) are not detected, at least at onset, in sporadic cases with acute manifestations. Testing for additional viral antigens or RNA and a longer follow-up period would be required before exclusion of a role for HCV in acute disease. Alternatively, other viral and non-viral agents may be sought in this illness.", "contents": "Serodiagnosis of hepatitis C in acute and chronic liver disease in southwestern Saudi Arabia. The extent of involvement of hepatitis C, as compared to hepatitis A and hepatitis B, virus infection in acute and chronic liver disease in the Asir Region, southwestern Saudi Arabia, was assessed in 898 patients hospitalized during the period from June 1990 to November 1991. Acute icteric hepatitis cases with severe onset were distinguished by their referral to the fever hospital while cases with milder onset and those with chronic hepatitis were followed at two general hospitals. Antibodies to the c-100-3 antigen of hepatitis C virus (anti HCV) were detected in a significant proportion of patients with chronic liver disease (chronic active hepatitis (65%), cirrhosis (44%)). Anti HCV was also detected in patients with acute hepatitis with milder onset at the general hospitals (10.9%) but proportionately much less in patients at the fever referral hospital (< 1%) where hepatitis A (52%) and, to a lesser extent hepatitis B (11%), were mostly diagnosed. These results indicate that HCV is a major identifiable infection in hospitalized patients with chronic liver disease in this region but that anti HCV antibodies (c-100-3) are not detected, at least at onset, in sporadic cases with acute manifestations. Testing for additional viral antigens or RNA and a longer follow-up period would be required before exclusion of a role for HCV in acute disease. Alternatively, other viral and non-viral agents may be sought in this illness."} {"id": "PMID:1281242", "title": "[Hepatic protein synthesis and cytokines in obstructive jaundice].", "content": "To clarify the mechanism of the increase of hepatic protein synthesis observed in the obstructive jaundiced rats, hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were estimated in the rats with obstructive jaundice and the contents of the following in the peripheral blood were determined in 21 patients with obstructive jaundice before and two weeks after percutaneous transhepatic biliary drainage (PTBD): interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), endotoxin (Et), acute-phase protein (APP) and negative acute-phase protein (NAPP). (1) HPS and SPS were markedly increased by obstructive jaundice; (2) IL-1 beta and IL-6 were significantly high and were reduced after PTBD; (3) neither TNF alpha nor Et was detected; (4) APP were significantly high and failed to decline after PTBD; (5) NAPP were significantly low and the contents were restored to the normal levels after PTBD. These results suggest that increased hepatic protein synthesis observed in the rats with obstructive jaundice correspond to the increased hepatic production of APP in patients with obstructive jaundice.", "contents": "[Hepatic protein synthesis and cytokines in obstructive jaundice]. To clarify the mechanism of the increase of hepatic protein synthesis observed in the obstructive jaundiced rats, hepatocellular protein synthesis (HPS) and secretory protein synthesis (SPS) were estimated in the rats with obstructive jaundice and the contents of the following in the peripheral blood were determined in 21 patients with obstructive jaundice before and two weeks after percutaneous transhepatic biliary drainage (PTBD): interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF alpha), endotoxin (Et), acute-phase protein (APP) and negative acute-phase protein (NAPP). (1) HPS and SPS were markedly increased by obstructive jaundice; (2) IL-1 beta and IL-6 were significantly high and were reduced after PTBD; (3) neither TNF alpha nor Et was detected; (4) APP were significantly high and failed to decline after PTBD; (5) NAPP were significantly low and the contents were restored to the normal levels after PTBD. These results suggest that increased hepatic protein synthesis observed in the rats with obstructive jaundice correspond to the increased hepatic production of APP in patients with obstructive jaundice."} {"id": "PMID:1281243", "title": "[Dysuria in male elderly outpatients evaluated by a questionnaire survey].", "content": "We surveyed complaints of dysuria in male elderly outpatients by questionnaire survey. Seven hundred and twenty outpatients (39 aged 30-39, 63 aged 40-49, 170 aged 50-59, 229 aged 60-69, and 219 aged 70 or more) visiting our outpatient internal medicine clinics were asked by a questionnaire about the subjective symptoms of dysuria, including frequencies of nocturia, prolongation of the start of urination, straining at urination, and residual urine, graded as asymptomatic, mild, moderate and severe. The subjects were divided into three groups as to the dysuria; normal group without symptoms or one mild symptom, borderline group with two or more mild symptoms, and dysuria group with one moderate or severe symptom or more. The rates of the patients in the dysuria group were increased with age, being 15%, 16%, 21%, 31% and 53%, respectively, in the above-mentioned age groups. This finding emphasized the importance of questions about dysuria in elderly patients also in internal medicine outpatient clinics, and of differential diagnosis for the causal factor(s) for dysuria in elderly patients including benign prostate hypertrophy.", "contents": "[Dysuria in male elderly outpatients evaluated by a questionnaire survey]. We surveyed complaints of dysuria in male elderly outpatients by questionnaire survey. Seven hundred and twenty outpatients (39 aged 30-39, 63 aged 40-49, 170 aged 50-59, 229 aged 60-69, and 219 aged 70 or more) visiting our outpatient internal medicine clinics were asked by a questionnaire about the subjective symptoms of dysuria, including frequencies of nocturia, prolongation of the start of urination, straining at urination, and residual urine, graded as asymptomatic, mild, moderate and severe. The subjects were divided into three groups as to the dysuria; normal group without symptoms or one mild symptom, borderline group with two or more mild symptoms, and dysuria group with one moderate or severe symptom or more. The rates of the patients in the dysuria group were increased with age, being 15%, 16%, 21%, 31% and 53%, respectively, in the above-mentioned age groups. This finding emphasized the importance of questions about dysuria in elderly patients also in internal medicine outpatient clinics, and of differential diagnosis for the causal factor(s) for dysuria in elderly patients including benign prostate hypertrophy."} {"id": "PMID:1281244", "title": "Angiogenesis can be stimulated or repressed in vivo by a change in GM3:GD3 ganglioside ratio.", "content": "We had previously observed that rabbit cornea stimulated by an angiogenic factor 1) became richer in total gangliosides and 2) reduced the GM3:GD3 ganglioside ratio. Moreover, experimentally induced global enrichment of corneal gangliosides favors angiogenesis. The objective of this work was to explain the possible relationship between angiogenic response and changes in the GM3:GD3 ratios observed in vivo. Cornea was utilized because it is avascular and transparent; i.e., the onset of opacity permitted exclusion of angiogenesis produced by a generic inflammatory response. Prostaglandin E1 or basic fibroblast growth factor were applied as angiogenesis triggers. Angiogenesis in vivo and mobilization and growth of microvascular endothelium in vitro were taken as parameters to indicate whether differences in GM3:GD3 ratios could modify the extent of the angiogenic response. In vivo angiogenesis, whether prostaglandin E1 or basic fibroblast growth factor induced, was repressed by GM3 and enhanced by GD3 or GM1 enrichment of the cornea. In vitro growth and motility of microvascular endothelium were reduced by GM3 addition to the medium and returned to normal levels by addition of GD3. Formation of new vessels induced by two different angiogenic factors could be stimulated or repressed in the cornea by reduction or enhancement of the GM3:GD3 ratio of tissue gangliosides. Changes in the relative proportion of molecules normally present in adult tissues, like prostaglandin E1, basic fibroblast growth factor, GM3, GD3, were sufficient to modulate or even block angiogenesis.", "contents": "Angiogenesis can be stimulated or repressed in vivo by a change in GM3:GD3 ganglioside ratio. We had previously observed that rabbit cornea stimulated by an angiogenic factor 1) became richer in total gangliosides and 2) reduced the GM3:GD3 ganglioside ratio. Moreover, experimentally induced global enrichment of corneal gangliosides favors angiogenesis. The objective of this work was to explain the possible relationship between angiogenic response and changes in the GM3:GD3 ratios observed in vivo. Cornea was utilized because it is avascular and transparent; i.e., the onset of opacity permitted exclusion of angiogenesis produced by a generic inflammatory response. Prostaglandin E1 or basic fibroblast growth factor were applied as angiogenesis triggers. Angiogenesis in vivo and mobilization and growth of microvascular endothelium in vitro were taken as parameters to indicate whether differences in GM3:GD3 ratios could modify the extent of the angiogenic response. In vivo angiogenesis, whether prostaglandin E1 or basic fibroblast growth factor induced, was repressed by GM3 and enhanced by GD3 or GM1 enrichment of the cornea. In vitro growth and motility of microvascular endothelium were reduced by GM3 addition to the medium and returned to normal levels by addition of GD3. Formation of new vessels induced by two different angiogenic factors could be stimulated or repressed in the cornea by reduction or enhancement of the GM3:GD3 ratio of tissue gangliosides. Changes in the relative proportion of molecules normally present in adult tissues, like prostaglandin E1, basic fibroblast growth factor, GM3, GD3, were sufficient to modulate or even block angiogenesis."} {"id": "PMID:1281241", "title": "The health of children adopted from Romania.", "content": "To determine the medical condition of Romanian adoptees and the effects of the Romanian orphanage system on their health. Case series. The international adoption clinics at the University of Minnesota, Minneapolis, and the New England Medical Center, Tufts University, Boston, Mass. Sixty-five Romanian adoptees who were brought to the United States during a 12-month period beginning in October 1990. Incidence of hepatitis B, intestinal parasites, tuberculosis, syphilis, human immunodeficiency virus type 1, growth failure, and developmental delay. Although the adopted children were presumably chosen from the most vital and attractive adoptees, only 15% were judged to be physically healthy and developmentally normal. Fifty-three percent had serological evidence of past or present hepatitis B infection, and 20% of screened children tested positive for hepatitis B surface antigen. In children aged 7 months or older, the overall prevalence of chronic hepatitis B was 23%. Intestinal parasites were found in 33% of subjects, and 45% of infected children had two or more pathogens identified. All the children tested for human immunodeficiency virus type 1 were negative. Two patterns of growth failure were observed that resembled the two subtypes of psychosocial short stature that occur in association with prolonged psychological harassment or emotional deprivation. Infants' length, weight, head circumference, and weight-for-height were adversely affected by institutionalization. Older children's height was reduced. Only 10% of children older than 12 months were developmentally normal. Romanian adoptees are an extraordinarily high-risk pediatric group as a consequences of decades of government-sanctioned child neglect and abuse.", "contents": "The health of children adopted from Romania. To determine the medical condition of Romanian adoptees and the effects of the Romanian orphanage system on their health. Case series. The international adoption clinics at the University of Minnesota, Minneapolis, and the New England Medical Center, Tufts University, Boston, Mass. Sixty-five Romanian adoptees who were brought to the United States during a 12-month period beginning in October 1990. Incidence of hepatitis B, intestinal parasites, tuberculosis, syphilis, human immunodeficiency virus type 1, growth failure, and developmental delay. Although the adopted children were presumably chosen from the most vital and attractive adoptees, only 15% were judged to be physically healthy and developmentally normal. Fifty-three percent had serological evidence of past or present hepatitis B infection, and 20% of screened children tested positive for hepatitis B surface antigen. In children aged 7 months or older, the overall prevalence of chronic hepatitis B was 23%. Intestinal parasites were found in 33% of subjects, and 45% of infected children had two or more pathogens identified. All the children tested for human immunodeficiency virus type 1 were negative. Two patterns of growth failure were observed that resembled the two subtypes of psychosocial short stature that occur in association with prolonged psychological harassment or emotional deprivation. Infants' length, weight, head circumference, and weight-for-height were adversely affected by institutionalization. Older children's height was reduced. Only 10% of children older than 12 months were developmentally normal. Romanian adoptees are an extraordinarily high-risk pediatric group as a consequences of decades of government-sanctioned child neglect and abuse."} {"id": "PMID:1281245", "title": "Distribution and cellular origin of undulin in rat liver.", "content": "Undulin is a novel large glycoprotein of the interstitial extracellular matrix belonging to the fibronectin-tenascin glycoprotein gene family. The distribution in diseased liver and the cellular origin of this protein are unknown. Immunohistochemistry studies were performed on cryostat sections of normal and damaged rat livers (CCl4 model). Hepatocytes, Kupffer cells, fat-storing cells (FSC), and sinusoidal endothelial cells (EC) were isolated by standard methods and kept in culture. Undulin biosynthesis in vitro was studied by indirect immunofluorescence and by immunoprecipitation of endogenously labeled protein followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Undulin was demonstrated in portal stroma, in vascular adventitia, and inside the space of Disse of normal liver. Acutely and chronically damaged livers revealed strong staining reactions in damaged areas, scars, and sinusoids. The overall distribution of undulin resembled the pattern noted for fibronectin. In contrast to undulin, tenascin was not detectable within the adventitia of vascular and ductular structures of normal and damaged livers, and tenascin accumulated preferentially at scar-parenchyma interfaces in fibrotic livers. In vivo, desmin and smooth muscle alpha-actin positive cells were in part codistributed with undulin fibers as shown by double staining techniques. In vitro, undulin was detected in granules of freshly isolated FSCs and ECs and was localized as fibers in the extracellular matrix of cultivated FSCs and ECs. Synthesis of undulin was demonstrated by immunoprecipitation of the protein from cultured FSCs and ECs. No experimental evidence was found for undulin synthesis in vitro by hepatocytes and Kupffer cells. The novel glycoprotein undulin is present in the normal rat liver and accumulates during acute and chronic liver injury. Our results suggest that among the resident cells of the liver, FSCs and ECs are the major sources of undulin.", "contents": "Distribution and cellular origin of undulin in rat liver. Undulin is a novel large glycoprotein of the interstitial extracellular matrix belonging to the fibronectin-tenascin glycoprotein gene family. The distribution in diseased liver and the cellular origin of this protein are unknown. Immunohistochemistry studies were performed on cryostat sections of normal and damaged rat livers (CCl4 model). Hepatocytes, Kupffer cells, fat-storing cells (FSC), and sinusoidal endothelial cells (EC) were isolated by standard methods and kept in culture. Undulin biosynthesis in vitro was studied by indirect immunofluorescence and by immunoprecipitation of endogenously labeled protein followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography. Undulin was demonstrated in portal stroma, in vascular adventitia, and inside the space of Disse of normal liver. Acutely and chronically damaged livers revealed strong staining reactions in damaged areas, scars, and sinusoids. The overall distribution of undulin resembled the pattern noted for fibronectin. In contrast to undulin, tenascin was not detectable within the adventitia of vascular and ductular structures of normal and damaged livers, and tenascin accumulated preferentially at scar-parenchyma interfaces in fibrotic livers. In vivo, desmin and smooth muscle alpha-actin positive cells were in part codistributed with undulin fibers as shown by double staining techniques. In vitro, undulin was detected in granules of freshly isolated FSCs and ECs and was localized as fibers in the extracellular matrix of cultivated FSCs and ECs. Synthesis of undulin was demonstrated by immunoprecipitation of the protein from cultured FSCs and ECs. No experimental evidence was found for undulin synthesis in vitro by hepatocytes and Kupffer cells. The novel glycoprotein undulin is present in the normal rat liver and accumulates during acute and chronic liver injury. Our results suggest that among the resident cells of the liver, FSCs and ECs are the major sources of undulin."} {"id": "PMID:1281246", "title": "A parallel computation revealing the role of the in vivo environment in shaping the catalytic structure of a mitochondrial RNA transcript.", "content": "We study the search for folded structures performed by an RNA molecule as it is being assembled by sequential incorporation of nucleotides. The specific process we shall focus on is the transcription of intron 4 of the yeast apocytochrome b gene. We prove that the structure generated by sequential folding is endowed with catalytic potential. More specifically, the formation of all conserved interactions in the catalytic core and intramolecular splicing substrate may be achieved by sequential folding in vivo, concurrent with transcription itself. We base our analysis on a parallel Monte Carlo simulation, assigning an individual processor to each competing folding pathway. In this way, we show that the group I mitochondrial intron requires an in vivo environment to aid the folding into a structure presenting the catalytically-active helix P7 and the splicing substrate upon which the catalytic core exerts its function. It is inferred that a base pair disruption caused by interaction with a ribosome is required to bias the folding pathway so that helix P7 is formed. Furthermore, it is shown that a disruption in the early stages of transcription, followed by the perturbation described is essential to shape the 3' splicing site. Our study suggests that pre-mRNAs of group I might achieve catalytic potential in a fundamentally different way from ribosomal RNAs of the same group, where thermodynamics appear to control the formation of the catalytic structural motif. The role of the trans-acting factor, on the other hand, cannot be recovered in vitro by recombination with the transcript.", "contents": "A parallel computation revealing the role of the in vivo environment in shaping the catalytic structure of a mitochondrial RNA transcript. We study the search for folded structures performed by an RNA molecule as it is being assembled by sequential incorporation of nucleotides. The specific process we shall focus on is the transcription of intron 4 of the yeast apocytochrome b gene. We prove that the structure generated by sequential folding is endowed with catalytic potential. More specifically, the formation of all conserved interactions in the catalytic core and intramolecular splicing substrate may be achieved by sequential folding in vivo, concurrent with transcription itself. We base our analysis on a parallel Monte Carlo simulation, assigning an individual processor to each competing folding pathway. In this way, we show that the group I mitochondrial intron requires an in vivo environment to aid the folding into a structure presenting the catalytically-active helix P7 and the splicing substrate upon which the catalytic core exerts its function. It is inferred that a base pair disruption caused by interaction with a ribosome is required to bias the folding pathway so that helix P7 is formed. Furthermore, it is shown that a disruption in the early stages of transcription, followed by the perturbation described is essential to shape the 3' splicing site. Our study suggests that pre-mRNAs of group I might achieve catalytic potential in a fundamentally different way from ribosomal RNAs of the same group, where thermodynamics appear to control the formation of the catalytic structural motif. The role of the trans-acting factor, on the other hand, cannot be recovered in vitro by recombination with the transcript."} {"id": "PMID:1281248", "title": "[Palliative care in cancer patients. Frequency and priority of symptoms].", "content": "The presence of multiple symptoms is very frequent in patients with advanced cancer disease. In this situation in which cure is not a realistic aim, the goal is to achieve symptom control and to give support to the patient and family. This study was designed to identify the most common and priority symptoms in patients with advanced cancer. Patients were given a questionnaire with a list of symptoms and were asked to underline those they presented, and also number those they considered most distressful from 1-3. Physicians and nurse independently answered the same questionnaire. Asthenia was the most frequent symptom (patient evaluation 84%, nurse 82% and doctor 93%). Psychopathological disturbances showed a high prevalence. Regarding patient evaluation, dry mouth was the third symptom in frequency (73%), but it was detected by nurses in 39% and by physicians in 16%. Priority symptoms for the three groups were pain, asthenia, anorexia and anxiety. Pain was controlled in 19/22 patients (86%), while psychopathological symptoms were only controlled in 7/19 patients (27%). In order to optimize treatment patient participation is mandatory. An interdisciplinary team (physicians, nurses, social workers, and psychologists) is necessary to take care of these patients.", "contents": "[Palliative care in cancer patients. Frequency and priority of symptoms]. The presence of multiple symptoms is very frequent in patients with advanced cancer disease. In this situation in which cure is not a realistic aim, the goal is to achieve symptom control and to give support to the patient and family. This study was designed to identify the most common and priority symptoms in patients with advanced cancer. Patients were given a questionnaire with a list of symptoms and were asked to underline those they presented, and also number those they considered most distressful from 1-3. Physicians and nurse independently answered the same questionnaire. Asthenia was the most frequent symptom (patient evaluation 84%, nurse 82% and doctor 93%). Psychopathological disturbances showed a high prevalence. Regarding patient evaluation, dry mouth was the third symptom in frequency (73%), but it was detected by nurses in 39% and by physicians in 16%. Priority symptoms for the three groups were pain, asthenia, anorexia and anxiety. Pain was controlled in 19/22 patients (86%), while psychopathological symptoms were only controlled in 7/19 patients (27%). In order to optimize treatment patient participation is mandatory. An interdisciplinary team (physicians, nurses, social workers, and psychologists) is necessary to take care of these patients."} {"id": "PMID:1281252", "title": "Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam.", "content": "GluR1 and GluR2 cDNAs encoding non-NMDA subtypes of glutamate receptor were isolated from a rat brain cDNA library by Boulter et al. (Science, 249 (1990) 1033-1037). Functional receptors activated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and glutamate were expressed in Xenopus oocytes injected with GluR1, GluR2 or a mixture of GluR1 and GluR2 RNAs. In GluR1-expressed oocytes, 1 mM aniracetam potentiated AMPA-induced currents by 99 +/- 10% (mean +/- S.E.M., n = 5) and glutamate-induced currents by 140 +/- 8% (n = 4), but little affected kainate-induced currents. Aniracetam was effective from a concentration of 0.1 mM, and it exhibited more conspicuous effects with the increase of the dose. In oocytes injected with GluR1 plus GluR2 RNAs, aniracetam more markedly potentiated current responses to AMPA and glutamate than those in oocytes injected with GluR1 RNA alone. For example, 1 mM aniracetam potentiated AMPA-induced currents by 396 +/- 76% (n = 4) and glutamate-induced currents by 970 +/- 65% (n = 5) in oocytes injected with 10% GluR1 and 90% GluR2 RNAs. In these oocytes, however, the potentiation of kainate-induced currents by 1 mM aniracetam was only 8 +/- 5% (n = 4). Thus, we conclude that the potentiation of the AMPA/kainate receptor by aniracetam depends on both species of agonists and subunit composition of the receptor.", "contents": "Agonist- and subunit-dependent potentiation of glutamate receptors by a nootropic drug aniracetam. GluR1 and GluR2 cDNAs encoding non-NMDA subtypes of glutamate receptor were isolated from a rat brain cDNA library by Boulter et al. (Science, 249 (1990) 1033-1037). Functional receptors activated by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and glutamate were expressed in Xenopus oocytes injected with GluR1, GluR2 or a mixture of GluR1 and GluR2 RNAs. In GluR1-expressed oocytes, 1 mM aniracetam potentiated AMPA-induced currents by 99 +/- 10% (mean +/- S.E.M., n = 5) and glutamate-induced currents by 140 +/- 8% (n = 4), but little affected kainate-induced currents. Aniracetam was effective from a concentration of 0.1 mM, and it exhibited more conspicuous effects with the increase of the dose. In oocytes injected with GluR1 plus GluR2 RNAs, aniracetam more markedly potentiated current responses to AMPA and glutamate than those in oocytes injected with GluR1 RNA alone. For example, 1 mM aniracetam potentiated AMPA-induced currents by 396 +/- 76% (n = 4) and glutamate-induced currents by 970 +/- 65% (n = 5) in oocytes injected with 10% GluR1 and 90% GluR2 RNAs. In these oocytes, however, the potentiation of kainate-induced currents by 1 mM aniracetam was only 8 +/- 5% (n = 4). Thus, we conclude that the potentiation of the AMPA/kainate receptor by aniracetam depends on both species of agonists and subunit composition of the receptor."} {"id": "PMID:1281253", "title": "Increased expression of preprotachykinin, calcitonin gene-related peptide, but not vasoactive intestinal peptide messenger RNA in dorsal root ganglia during the development of adjuvant monoarthritis in the rat.", "content": "Neuropeptides in dorsal root ganglia (DRG) have been implicated in the pathogenesis of pain and neurogenic inflammation in experimental and clinical arthritis. Recently we demonstrated increased levels of substance P (SP) and calcitonin gene-related peptide (CGRP) confined to innervating DRG in adjuvant-mediated monoarthritis. We have now investigated whether changes in peptide content are reflected in altered neuropeptide gene expression and the time course involved. Using in situ hybridization we found marked increases in expression of beta-preprotachykinin (PPT; 81 +/- 24% rise) and alpha-CGRP (44 +/- 6% rise) mRNAs in innervating (ipsilateral L5) DRG neurones only. These increases occurred at the onset of acute inflammation (8 h) and persisted until chronic arthritis developed after 14 days. There were no changes in the proportion of DRG neurones expressing PPT or CGRP mRNAs. Messenger RNA encoding vasoactive intestinal polypeptide (VIP) was not induced. These data suggest that increased synthesis of PPT and CGRP peptides in DRG may play a role in the pathogenesis both of adjuvant-mediated acute inflammation and chronic arthritis.", "contents": "Increased expression of preprotachykinin, calcitonin gene-related peptide, but not vasoactive intestinal peptide messenger RNA in dorsal root ganglia during the development of adjuvant monoarthritis in the rat. Neuropeptides in dorsal root ganglia (DRG) have been implicated in the pathogenesis of pain and neurogenic inflammation in experimental and clinical arthritis. Recently we demonstrated increased levels of substance P (SP) and calcitonin gene-related peptide (CGRP) confined to innervating DRG in adjuvant-mediated monoarthritis. We have now investigated whether changes in peptide content are reflected in altered neuropeptide gene expression and the time course involved. Using in situ hybridization we found marked increases in expression of beta-preprotachykinin (PPT; 81 +/- 24% rise) and alpha-CGRP (44 +/- 6% rise) mRNAs in innervating (ipsilateral L5) DRG neurones only. These increases occurred at the onset of acute inflammation (8 h) and persisted until chronic arthritis developed after 14 days. There were no changes in the proportion of DRG neurones expressing PPT or CGRP mRNAs. Messenger RNA encoding vasoactive intestinal polypeptide (VIP) was not induced. These data suggest that increased synthesis of PPT and CGRP peptides in DRG may play a role in the pathogenesis both of adjuvant-mediated acute inflammation and chronic arthritis."} {"id": "PMID:1281254", "title": "Prolactin receptor messenger RNA is synthesized by the epithelial cells of the choroid plexus.", "content": "To identify cellular sites of prolactin receptor messenger RNA synthesis in the rat brain, we used a combined reverse transcriptase-polymerase chain reaction protocol to generate single stranded DNA probes for in situ hybridization. The results of these experiments identify the epithelial cells of the choroid plexus as a major site of prolactin receptor gene expression in the rat central nervous system.", "contents": "Prolactin receptor messenger RNA is synthesized by the epithelial cells of the choroid plexus. To identify cellular sites of prolactin receptor messenger RNA synthesis in the rat brain, we used a combined reverse transcriptase-polymerase chain reaction protocol to generate single stranded DNA probes for in situ hybridization. The results of these experiments identify the epithelial cells of the choroid plexus as a major site of prolactin receptor gene expression in the rat central nervous system."} {"id": "PMID:1281255", "title": "Molecular and electrophysiological characterization of a allelic variant of the rat alpha 6 GABAA receptor subunit.", "content": "A 1.45 kb DNA sequence encoding the rat alpha 6 GABAA receptor subunit (nucleotides 33-1483) was cloned from a Sprague-Dawley rat brain cDNA library by PCR amplification. Dideoxy sequencing of two individual clones revealed that the nucleotide sequence differed at only one basepair (T480-->G) from that published previously. This difference altered the deduced amino acid sequence, producing a conservative amino acid substitution (His121-->Gln). A Gln residue is present at the same location in the bovine alpha 6 subunit. Restriction endonuclease analysis of the total PCR product demonstrated that this variant of the rat alpha 6 subunit was the only allele found in this particular rat brain library, the original allele was not present. These results were further verified by RNAse protection assays performed with RNA isolated from individual rat cerebella. alpha 6, beta 1, and gamma 2S subunits were transiently expressed in L929 cells for electrophysiological analysis. Whole-cell recordings obtained from the cells demonstrated that GABAA receptor channels with the expected GABA and benzodiazepine pharmacology were produced. Excised outside out single channel recordings from the same cells revealed that GABA elicited brief duration openings to a 33 pS main conductance level and to at least one smaller (approximately 21 pS) subconductance level. Thus this allelic variant of rat alpha 6 subunit could assemble with other subunits to form a functional GABAA receptor channel with similar properties to the original allelic form.", "contents": "Molecular and electrophysiological characterization of a allelic variant of the rat alpha 6 GABAA receptor subunit. A 1.45 kb DNA sequence encoding the rat alpha 6 GABAA receptor subunit (nucleotides 33-1483) was cloned from a Sprague-Dawley rat brain cDNA library by PCR amplification. Dideoxy sequencing of two individual clones revealed that the nucleotide sequence differed at only one basepair (T480-->G) from that published previously. This difference altered the deduced amino acid sequence, producing a conservative amino acid substitution (His121-->Gln). A Gln residue is present at the same location in the bovine alpha 6 subunit. Restriction endonuclease analysis of the total PCR product demonstrated that this variant of the rat alpha 6 subunit was the only allele found in this particular rat brain library, the original allele was not present. These results were further verified by RNAse protection assays performed with RNA isolated from individual rat cerebella. alpha 6, beta 1, and gamma 2S subunits were transiently expressed in L929 cells for electrophysiological analysis. Whole-cell recordings obtained from the cells demonstrated that GABAA receptor channels with the expected GABA and benzodiazepine pharmacology were produced. Excised outside out single channel recordings from the same cells revealed that GABA elicited brief duration openings to a 33 pS main conductance level and to at least one smaller (approximately 21 pS) subconductance level. Thus this allelic variant of rat alpha 6 subunit could assemble with other subunits to form a functional GABAA receptor channel with similar properties to the original allelic form."} {"id": "PMID:1281256", "title": "Administration of quinolinic acid in the rat hippocampus induces expression of c-fos and NGFI-A.", "content": "We have studied the effect of intrahippocampal administration of quinolinic acid (QUIN) on the temporal expression of mRNAs encoding the immediate early genes (IEGs) c-fos and NGFI-A, by in situ hybridization histochemistry. After administration of QUIN to the left hippocampus, expression of mRNA of both IEGs was transiently stimulated. Maximal expression was found between 1 and 3 h. mRNA of both IEGs was simultaneously expressed in the ipsilateral and contralateral sides in the granule cell layer of the dentate gyrus, the pyramidal cell layer of the CA1 and CA3 fields as well as in the cortex. After pretreatment with the non-competitive NMDA antagonist MK-801 (2 mg/kg i.p. -30 min) the increased expression of both IEGs was partially prevented in the hippocampus and completely in the cortex. No inhibition was observed after treatment with the AMPA antagonist NBQX (30 mg/kg i.p. -15, -5 and +10 min). Additional delayed expression of both IEGs was observed in the ipsilateral hippocampus. This expression was related to cell damage. Twelve h after QUIN administration, c-fos and NGFI-A mRNAs were present in the dentate gyrus. After 4 days, only c-fos mRNA was observed in the dentate gyrus and CA1 field while no NGFI-A mRNA was detected. The present results show that the effect of QUIN is mediated by NMDA and not by AMPA receptors.", "contents": "Administration of quinolinic acid in the rat hippocampus induces expression of c-fos and NGFI-A. We have studied the effect of intrahippocampal administration of quinolinic acid (QUIN) on the temporal expression of mRNAs encoding the immediate early genes (IEGs) c-fos and NGFI-A, by in situ hybridization histochemistry. After administration of QUIN to the left hippocampus, expression of mRNA of both IEGs was transiently stimulated. Maximal expression was found between 1 and 3 h. mRNA of both IEGs was simultaneously expressed in the ipsilateral and contralateral sides in the granule cell layer of the dentate gyrus, the pyramidal cell layer of the CA1 and CA3 fields as well as in the cortex. After pretreatment with the non-competitive NMDA antagonist MK-801 (2 mg/kg i.p. -30 min) the increased expression of both IEGs was partially prevented in the hippocampus and completely in the cortex. No inhibition was observed after treatment with the AMPA antagonist NBQX (30 mg/kg i.p. -15, -5 and +10 min). Additional delayed expression of both IEGs was observed in the ipsilateral hippocampus. This expression was related to cell damage. Twelve h after QUIN administration, c-fos and NGFI-A mRNAs were present in the dentate gyrus. After 4 days, only c-fos mRNA was observed in the dentate gyrus and CA1 field while no NGFI-A mRNA was detected. The present results show that the effect of QUIN is mediated by NMDA and not by AMPA receptors."} {"id": "PMID:1281257", "title": "Influence of a single injection of cocaine, amphetamine or GBR 12909 on mRNA expression of striatal neuropeptides.", "content": "The acute and long-term effects of a single injection of psychomotor stimulants (amphetamine (1.5 mg/kg i.p.), cocaine (30 mg/kg i.p.) and GBR 12909 (10 mg/kg i.p.)) were studied with in situ hybridization histochemistry to assess alterations in the mRNA expression of enkephalin, dynorphin and substance P in the striatum. The greatest alterations on mRNA levels of enkephalin, dynorphin and substance P were observed 2 h following the first administration of each drug compared to that observed following a second challenge injection 14 days later. Of the drugs tested, the dopamine uptake inhibitory agents cocaine and GBR 12909 acutely elevated mRNA levels of all three neuropeptides, while amphetamine elevated mRNA levels of substance P only. A second challenge administration of the stimulants 14 days subsequent to the initial single injection re-elevated the mRNA level of substance P. An overall tolerance is speculated to account for diminution of the enkephalin and dynorphin responses to a challenge injection while a relative sensitization is suggested for the enkephalin response due to a reduction in the baseline level of expression produced by the first injection. The data also show that there are regional variation within the striatum following systemic administration of psychomotor stimulants, with greater elevations in the sensorimotor dorsolateral striatum than in the ventromedial 'limbic' nucleus accumbens region.", "contents": "Influence of a single injection of cocaine, amphetamine or GBR 12909 on mRNA expression of striatal neuropeptides. The acute and long-term effects of a single injection of psychomotor stimulants (amphetamine (1.5 mg/kg i.p.), cocaine (30 mg/kg i.p.) and GBR 12909 (10 mg/kg i.p.)) were studied with in situ hybridization histochemistry to assess alterations in the mRNA expression of enkephalin, dynorphin and substance P in the striatum. The greatest alterations on mRNA levels of enkephalin, dynorphin and substance P were observed 2 h following the first administration of each drug compared to that observed following a second challenge injection 14 days later. Of the drugs tested, the dopamine uptake inhibitory agents cocaine and GBR 12909 acutely elevated mRNA levels of all three neuropeptides, while amphetamine elevated mRNA levels of substance P only. A second challenge administration of the stimulants 14 days subsequent to the initial single injection re-elevated the mRNA level of substance P. An overall tolerance is speculated to account for diminution of the enkephalin and dynorphin responses to a challenge injection while a relative sensitization is suggested for the enkephalin response due to a reduction in the baseline level of expression produced by the first injection. The data also show that there are regional variation within the striatum following systemic administration of psychomotor stimulants, with greater elevations in the sensorimotor dorsolateral striatum than in the ventromedial 'limbic' nucleus accumbens region."} {"id": "PMID:1281258", "title": "Proton relaxation studies of water compartmentalization in a model neurological system.", "content": "Proton relaxation measurements from 18 crayfish abdominal nerve cords (a model of human CNS) are used to demonstrate that the transverse (though not the longitudinal) relaxation can be decomposed into four reproducible components that, in conjunction with optical and electron microscopy of the morphology, can be assigned to three water compartments within the cord and possibly to the mobile lipid protons. The assignments are extraaxonal water protons (32 +/- 9% and mean T2 = 600 +/- 200 ms), axonal water protons (59 +/- 12% and mean T2 = 200 +/- 30 ms), intramyelinic water protons (7 +/- 4% and mean T2 = 50 +/- 20 ms), and finally an unsubstantiated assignment of lipid protons (2.0 +/- 2.0% and mean T2 = 7 +/- 4 ms).", "contents": "Proton relaxation studies of water compartmentalization in a model neurological system. Proton relaxation measurements from 18 crayfish abdominal nerve cords (a model of human CNS) are used to demonstrate that the transverse (though not the longitudinal) relaxation can be decomposed into four reproducible components that, in conjunction with optical and electron microscopy of the morphology, can be assigned to three water compartments within the cord and possibly to the mobile lipid protons. The assignments are extraaxonal water protons (32 +/- 9% and mean T2 = 600 +/- 200 ms), axonal water protons (59 +/- 12% and mean T2 = 200 +/- 30 ms), intramyelinic water protons (7 +/- 4% and mean T2 = 50 +/- 20 ms), and finally an unsubstantiated assignment of lipid protons (2.0 +/- 2.0% and mean T2 = 7 +/- 4 ms)."} {"id": "PMID:1281259", "title": "Effect of galanin on the growth hormone response to growth hormone-releasing hormone in acromegaly.", "content": "Galanin enhances growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in normal man. In acromegaly, circulating GH levels are increased and the GH response to GHRH may be exaggerated. Galanin has been recently shown to decrease circulating GH levels in acromegaly. The aim of our study was to investigate the effects of galanin on the GH response to GHRH in acromegalic subjects. Five acromegalic patients (three men and two women) and seven healthy adult subjects (five men and two women) were studied. GHRH-induced GH secretion was evaluated during a 40-minute intravenous (IV) infusion of saline (100 mL) or porcine galanin (12.5 micrograms/min in 100 mL saline). In normal subjects, delta GH levels after GHRH+porcine galanin administration (47 +/- 7.5 micrograms/L) were significantly higher in comparison to levels obtained with GHRH+saline (21.7 +/- 3.5 micrograms/L, P < .05). In acromegalic patients, GH responses to GHRH (delta GH, 18.8 +/- 8.6 micrograms/L) were not altered by galanin infusion (delta GH, 17.6 +/- 5 micrograms/L). Our results give the first evidence that the same dose of galanin that induces a significant enhancement of the GH response to GHRH in normal subjects has no effect on the GH response to GHRH in acromegalic patients. It can be hypothesized that galanin may interact at the pituitary level with its own receptors expressed by somatotropes independent of GHRH. Failure of galanin to enhance GH response to GHRH in acromegalic patients could be due to a change in function of the galanin receptor on GH-secreting adenomatous cells.", "contents": "Effect of galanin on the growth hormone response to growth hormone-releasing hormone in acromegaly. Galanin enhances growth hormone (GH)-releasing hormone (GHRH)-stimulated GH secretion in normal man. In acromegaly, circulating GH levels are increased and the GH response to GHRH may be exaggerated. Galanin has been recently shown to decrease circulating GH levels in acromegaly. The aim of our study was to investigate the effects of galanin on the GH response to GHRH in acromegalic subjects. Five acromegalic patients (three men and two women) and seven healthy adult subjects (five men and two women) were studied. GHRH-induced GH secretion was evaluated during a 40-minute intravenous (IV) infusion of saline (100 mL) or porcine galanin (12.5 micrograms/min in 100 mL saline). In normal subjects, delta GH levels after GHRH+porcine galanin administration (47 +/- 7.5 micrograms/L) were significantly higher in comparison to levels obtained with GHRH+saline (21.7 +/- 3.5 micrograms/L, P < .05). In acromegalic patients, GH responses to GHRH (delta GH, 18.8 +/- 8.6 micrograms/L) were not altered by galanin infusion (delta GH, 17.6 +/- 5 micrograms/L). Our results give the first evidence that the same dose of galanin that induces a significant enhancement of the GH response to GHRH in normal subjects has no effect on the GH response to GHRH in acromegalic patients. It can be hypothesized that galanin may interact at the pituitary level with its own receptors expressed by somatotropes independent of GHRH. Failure of galanin to enhance GH response to GHRH in acromegalic patients could be due to a change in function of the galanin receptor on GH-secreting adenomatous cells."} {"id": "PMID:1281260", "title": "DNA from bacteria, but not from vertebrates, induces interferons, activates natural killer cells and inhibits tumor growth.", "content": "The nucleic acid fraction from cells of 6 species of bacterium and 2 kinds of vertebrate, calf and salmon, was extracted and purified by the same procedures as described previously. When the spleen cells from BALB/c mice were incubated with the nucleic acid fraction from either of the bacteria, natural killer (NK) activity of the cells was remarkably elevated and the cells produced factors to activate macrophages and to inhibit viral growth. It was shown that the factor to activate macrophages was interferon (IFN)-gamma and that to inhibit viral growth was IFN-alpha/beta. On the other hand, the nucleic acid fraction from either of the vertebrate cells did not show such activities. Pretreatment of the bacterial nucleic acid fraction with DNase, but not with RNase, abrogated completely the biological activities. The activities of the bacterial nucleic acid were not influenced by the presence of polymyxin B, an inhibitor of lipopolysaccharide (LPS), and the spleen cells from not only BALB/c mice but also LPS-insensitive C3H/HeJ mice were activated, indicating that the activities of the fraction were not ascribed to LPS contaminated possibly into the fraction, but to DNA itself. Intralesional injection with the bacterial DNA fraction caused regression of mouse IMC tumors, but the injection with the vertebrate DNA fraction did not. These findings prompted us to examine the biological activities of DNA samples from a variety of animals and plants, which were provided from other laboratories or purchased from manufacturers. All of the DNA samples from cells of 5 kinds of bacterium, 2 of virus and 4 of invertebrate augmented NK activity and induced IFN, more or less, in mouse spleen calls, while the DNA from 10 kinds of vertebrate, including 3 of fish and 5 of mammal, showed no such activities. The DNA from 2 species of plants, were also inactive. Possible mechanisms to explain the different biological activities of DNA from different cell sources were discussed based on our previous finding that the particular palindromic sequences with a G-C motif(s) are required for induction of IFNs and activation of NK cells with synthetic 30-mer oligonucleotides.", "contents": "DNA from bacteria, but not from vertebrates, induces interferons, activates natural killer cells and inhibits tumor growth. The nucleic acid fraction from cells of 6 species of bacterium and 2 kinds of vertebrate, calf and salmon, was extracted and purified by the same procedures as described previously. When the spleen cells from BALB/c mice were incubated with the nucleic acid fraction from either of the bacteria, natural killer (NK) activity of the cells was remarkably elevated and the cells produced factors to activate macrophages and to inhibit viral growth. It was shown that the factor to activate macrophages was interferon (IFN)-gamma and that to inhibit viral growth was IFN-alpha/beta. On the other hand, the nucleic acid fraction from either of the vertebrate cells did not show such activities. Pretreatment of the bacterial nucleic acid fraction with DNase, but not with RNase, abrogated completely the biological activities. The activities of the bacterial nucleic acid were not influenced by the presence of polymyxin B, an inhibitor of lipopolysaccharide (LPS), and the spleen cells from not only BALB/c mice but also LPS-insensitive C3H/HeJ mice were activated, indicating that the activities of the fraction were not ascribed to LPS contaminated possibly into the fraction, but to DNA itself. Intralesional injection with the bacterial DNA fraction caused regression of mouse IMC tumors, but the injection with the vertebrate DNA fraction did not. These findings prompted us to examine the biological activities of DNA samples from a variety of animals and plants, which were provided from other laboratories or purchased from manufacturers. All of the DNA samples from cells of 5 kinds of bacterium, 2 of virus and 4 of invertebrate augmented NK activity and induced IFN, more or less, in mouse spleen calls, while the DNA from 10 kinds of vertebrate, including 3 of fish and 5 of mammal, showed no such activities. The DNA from 2 species of plants, were also inactive. Possible mechanisms to explain the different biological activities of DNA from different cell sources were discussed based on our previous finding that the particular palindromic sequences with a G-C motif(s) are required for induction of IFNs and activation of NK cells with synthetic 30-mer oligonucleotides."} {"id": "PMID:1281261", "title": "The philosophy of palliative medicine: a challenge for medical education.", "content": "The hospice movement has admirably improved management of the dying under its care. However, the majority of medical care of the terminally and chronically ill remains in the hands of practitioners outside hospices and is often open to criticism. This paper reviews the philosophy and practice of palliative medicine from the perspective of general practice and the shortcomings of present medical education in this area. Proposals are made for a radical shift in medical undergraduate teaching through an organized interdepartmental contribution by enthusiastic teachers to all years in training.", "contents": "The philosophy of palliative medicine: a challenge for medical education. The hospice movement has admirably improved management of the dying under its care. However, the majority of medical care of the terminally and chronically ill remains in the hands of practitioners outside hospices and is often open to criticism. This paper reviews the philosophy and practice of palliative medicine from the perspective of general practice and the shortcomings of present medical education in this area. Proposals are made for a radical shift in medical undergraduate teaching through an organized interdepartmental contribution by enthusiastic teachers to all years in training."} {"id": "PMID:1281262", "title": "Reconstitution and regulation of cation-selective channels from cardiac sarcoplasmic reticulum.", "content": "In order to study the conductances of the Sarcoplasmic Reticulum (SR) membrane, microsomal fractions from cardiac SR were isolated by differential and sucrose gradient centrifugations and fused into planar lipid bilayers (PLB) made of phospholipids. Using either KCl or K-gluconate solutions, a large conducting K+ selective channel was characterized by its ohmic conductance (152 pS in 150 mM K+), and the presence of short and long lasting subconducting states. Its open probability Po increased with depolarizing voltages, thus supporting the idea that this channel might allow counter-charge movements of monovalent cations during rapid SR Ca2+ release. An heterogeneity in the kinetic behavior of this channel would suggest that the cardiac SR K+ channels might be regulated by cytoplasmic, luminal, or intra SR membrane biochemical mechanisms. Since the behavior was not modified by variations of [Ca2+] nor by the addition of soluble metabolites such as ATP, GTP, cAMP, cGMP, nor by phosphorylation conditions on both sides of the PLB, a specific interaction with a SR membrane component is postulated. Another cation selective channel was studied in asymmetric Ca2+, Ba2+ or Mg(2+)-HEPES buffers. This channel displayed large conductance values for the above divalent cations 90, 100, and 40 pS, respectively. This channel was activated by microM Ca2+ while its Ca2+ sensitivity was potentiated by millimolar ATP. However Mg2+ and calmodulin modulated its gating behavior. Ca2+ releasing drugs such as caffeine and ryanodine increased its Po. All these features are characteristics of the SR Ca2+ release channel. The ryanodine receptor which has been purified and reconstituted into PLB, may form a cation selective pathway.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Reconstitution and regulation of cation-selective channels from cardiac sarcoplasmic reticulum. In order to study the conductances of the Sarcoplasmic Reticulum (SR) membrane, microsomal fractions from cardiac SR were isolated by differential and sucrose gradient centrifugations and fused into planar lipid bilayers (PLB) made of phospholipids. Using either KCl or K-gluconate solutions, a large conducting K+ selective channel was characterized by its ohmic conductance (152 pS in 150 mM K+), and the presence of short and long lasting subconducting states. Its open probability Po increased with depolarizing voltages, thus supporting the idea that this channel might allow counter-charge movements of monovalent cations during rapid SR Ca2+ release. An heterogeneity in the kinetic behavior of this channel would suggest that the cardiac SR K+ channels might be regulated by cytoplasmic, luminal, or intra SR membrane biochemical mechanisms. Since the behavior was not modified by variations of [Ca2+] nor by the addition of soluble metabolites such as ATP, GTP, cAMP, cGMP, nor by phosphorylation conditions on both sides of the PLB, a specific interaction with a SR membrane component is postulated. Another cation selective channel was studied in asymmetric Ca2+, Ba2+ or Mg(2+)-HEPES buffers. This channel displayed large conductance values for the above divalent cations 90, 100, and 40 pS, respectively. This channel was activated by microM Ca2+ while its Ca2+ sensitivity was potentiated by millimolar ATP. However Mg2+ and calmodulin modulated its gating behavior. Ca2+ releasing drugs such as caffeine and ryanodine increased its Po. All these features are characteristics of the SR Ca2+ release channel. The ryanodine receptor which has been purified and reconstituted into PLB, may form a cation selective pathway.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281263", "title": "Functional expression of renal organic anion transport in Xenopus laevis oocytes.", "content": "Secretion of organic anions by the kidney plays a critical role in the elimination of toxic agents from the body. Recent findings in isolated membranes and intact tissue have demonstrated the participation of multiple transport proteins in this process. As a first step toward molecular characterization of these proteins through expression cloning, the studies reported below demonstrate functional expression of both fumarate- and lithium-sensitive glutarate and probenecid-sensitive p-aminohippurate transport in Xenopus oocytes injected with rat kidney poly(A)+ RNA. Maximal increase in substrate uptake over buffer-injected controls was reached by 5 days after mRNA injection. Expression of size-fractionated mRNA indicated that the active species with respect to both transport activities were in the range of 1.8 to 3.5 kb.", "contents": "Functional expression of renal organic anion transport in Xenopus laevis oocytes. Secretion of organic anions by the kidney plays a critical role in the elimination of toxic agents from the body. Recent findings in isolated membranes and intact tissue have demonstrated the participation of multiple transport proteins in this process. As a first step toward molecular characterization of these proteins through expression cloning, the studies reported below demonstrate functional expression of both fumarate- and lithium-sensitive glutarate and probenecid-sensitive p-aminohippurate transport in Xenopus oocytes injected with rat kidney poly(A)+ RNA. Maximal increase in substrate uptake over buffer-injected controls was reached by 5 days after mRNA injection. Expression of size-fractionated mRNA indicated that the active species with respect to both transport activities were in the range of 1.8 to 3.5 kb."} {"id": "PMID:1281264", "title": "Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus.", "content": "Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Using whole-cell voltage clamp of single smooth muscle cells isolated from the longitudinal layer of 18-day pregnant rat uterus, depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow [8]. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o, and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current, and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. Thus, the ion channels which generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells which possess fast Na+ channels, and it is suggested that the fast Na+ current may be involved in spread of excitation. The Ca2+ channel current density also was higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and may facilitate parturition. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 of 12 mM) and nifedipine (K0.5 of 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extent. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions is not due to stimulation of ICa(s). Figure 11 summarizes the possible mechanisms by which uterine contractility can be modulated. In contrast to vascular smooth muscle, neither ISO nor adenosine, which produce elevation of cyclic AMP, affected ICa and INa. Therefore, no arrow can be drawn between cA-PK/cG-PK and the Ca2+ slow channel.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Fast Na+ channels and slow Ca2+ current in smooth muscle from pregnant rat uterus. Smooth muscle cells normally do not possess fast Na+ channels, but inward current is carried through two types of Ca2+ channels: slow (L-type) Ca2+ channels and fast (T-type) Ca2+ channels. Using whole-cell voltage clamp of single smooth muscle cells isolated from the longitudinal layer of 18-day pregnant rat uterus, depolarizing pulses, applied from a holding potential of -90 mV, evoked two types of inward current, fast and slow [8]. The fast inward current decayed within 30 ms, depended on [Na]o, and was inhibited by TTX (K0.5 = 27 nM). The slow inward current decayed slowly, was dependent on [Ca]o, and was inhibited by nifedipine. These results suggest that the fast inward current is a fast Na+ channel current, and that the slow inward current is a Ca2+ slow channel current. A fast-inactivating Ca2+ channel current was not evident. Thus, the ion channels which generate inward currents in pregnant rat uterine cells are TTX-sensitive fast Na+ channels and dihydropyridine-sensitive slow Ca2+ channels. The number of fast Na+ channels increased during gestation. The averaged current density increased from 0 on day 5, to 0.19 on day 9, to 0.56 on day 14, to 0.90 on day 18, and to 0.86 pA/pF on day 21. This almost linear increase occurs because of an increase in the fraction of cells which possess fast Na+ channels, and it is suggested that the fast Na+ current may be involved in spread of excitation. The Ca2+ channel current density also was higher during the latter half of gestation. These results indicate that the fast Na+ channels and Ca2+ slow channels in myometrium become more numerous as term approaches, and may facilitate parturition. Isoproterenol (beta-agonist) did not affect either ICa(s) or INa(f), whereas Mg2+ (K0.5 of 12 mM) and nifedipine (K0.5 of 3.3 nM) depressed ICa(s). Oxytocin had no effect on INa(f) and actually depressed ICa(s) to a small extent. Therefore, the tocolytic action of beta-agonists cannot be explained by an inhibition of ICa(s), whereas that of Mg2+ can be so explained. The stimulating action of oxytocin on uterine contractions is not due to stimulation of ICa(s). Figure 11 summarizes the possible mechanisms by which uterine contractility can be modulated. In contrast to vascular smooth muscle, neither ISO nor adenosine, which produce elevation of cyclic AMP, affected ICa and INa. Therefore, no arrow can be drawn between cA-PK/cG-PK and the Ca2+ slow channel.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281265", "title": "Detection of somatic mutations in vivo in lung fibroblasts, I. Spontaneous frequencies in Chinese hamsters and F344 rats.", "content": "The frequency of mutant cells observed in a series of experiments in which primary cells were isolated from untreated or solvent control animals are reported. The mutants detected are thioguanine-resistant lung fibroblasts isolated de novo from Chinese hamsters or Fischer 344 rats. The results in the two species were very similar. The distribution of mutant colonies in cells isolated from untreated animals is not random (Poissonian) but rather shows an excess of mutant clusters. No significant difference was detected between males and females. The results provide the information necessary to define the appropriate conditions for the negative controls for a routine assay for mutations induced in vivo.", "contents": "Detection of somatic mutations in vivo in lung fibroblasts, I. Spontaneous frequencies in Chinese hamsters and F344 rats. The frequency of mutant cells observed in a series of experiments in which primary cells were isolated from untreated or solvent control animals are reported. The mutants detected are thioguanine-resistant lung fibroblasts isolated de novo from Chinese hamsters or Fischer 344 rats. The results in the two species were very similar. The distribution of mutant colonies in cells isolated from untreated animals is not random (Poissonian) but rather shows an excess of mutant clusters. No significant difference was detected between males and females. The results provide the information necessary to define the appropriate conditions for the negative controls for a routine assay for mutations induced in vivo."} {"id": "PMID:1281266", "title": "Mutagenicity testing of protein-containing and biological samples using the Ames/Salmonella plate incorporation test and the fluctuation test.", "content": "Mutagenicity testing of biological samples and proteins is complicated by the presence of histidine and histidine-related growth factors which may produce a false positive result in the Ames/Salmonella plate incorporation test. A bioassay method, utilizing an automated dispenser-photometer and Salmonella typhimurium strain TA1535 as the indicator bacteria, was used to estimate the presence of histidine-related growth factors in three enzyme solutions submitted for mutagenicity testing. One of the solutions was clearly positive in the Ames/Salmonella test and also contained the highest amount of L-histidine-HCl-equivalents. The two other solutions, with low or undetectable amounts of L-histidine-HCl-equivalents, gave equivocal and negative results, respectively, in the Ames/Salmonella test. Studies were also performed with strains TA98, TA100 and TA1535 to determine the amount of added L-histidine-HCl that would result in a 'positive' result in the Ames/Salmonella test. Because the minimum amount of L-histidine-HCl required to double the number of revertant colonies was 150 nmol/plate, and the maximum amount of L-histidine-HCl-equivalents supplied by the enzyme preparations was 40 nmol/plate at the highest tested dose, the mutagenicity test results of the enzyme solutions cannot be explained solely by histidine or related compounds. Smokers' and non-smokers' urines, concentrated with liquid extraction (CHCl3) and adsorbent (XAD-2 and XAD-2/Sep-Pak C18) techniques, were studied to reveal differences in efficiencies to extract histidine and histidine-related compounds in the urines. Amounts of 'histidine' in concentrates of urine were measured using the bioassay method and a chemical method employing derivatization with fluorescamine. The fluorescamine method also efficiently detected 3-methyl-L-histidine, a product of muscle metabolism excreted in urine, which was found to be unable to support auxotrophic growth in TA1535, leading to exaggerated estimations of the auxotrophic growth enhancing properties of urine extracts. The urine extracts, and pure L-histidine-HCl, were tested using a two-step fluctuation test to estimate auxotrophic growth factor effects in this type of test. Because of a strong dilution effect when adding the histidine-free selection medium, the fluctuation test employed in this study was not found to be particularly sensitive to growth factors. The results of this study indicate that use of a bioassay, employing the same indicator bacteria as the mutagenicity test themselves, is a reliable way to measure histidine-related growth factors in biological samples.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Mutagenicity testing of protein-containing and biological samples using the Ames/Salmonella plate incorporation test and the fluctuation test. Mutagenicity testing of biological samples and proteins is complicated by the presence of histidine and histidine-related growth factors which may produce a false positive result in the Ames/Salmonella plate incorporation test. A bioassay method, utilizing an automated dispenser-photometer and Salmonella typhimurium strain TA1535 as the indicator bacteria, was used to estimate the presence of histidine-related growth factors in three enzyme solutions submitted for mutagenicity testing. One of the solutions was clearly positive in the Ames/Salmonella test and also contained the highest amount of L-histidine-HCl-equivalents. The two other solutions, with low or undetectable amounts of L-histidine-HCl-equivalents, gave equivocal and negative results, respectively, in the Ames/Salmonella test. Studies were also performed with strains TA98, TA100 and TA1535 to determine the amount of added L-histidine-HCl that would result in a 'positive' result in the Ames/Salmonella test. Because the minimum amount of L-histidine-HCl required to double the number of revertant colonies was 150 nmol/plate, and the maximum amount of L-histidine-HCl-equivalents supplied by the enzyme preparations was 40 nmol/plate at the highest tested dose, the mutagenicity test results of the enzyme solutions cannot be explained solely by histidine or related compounds. Smokers' and non-smokers' urines, concentrated with liquid extraction (CHCl3) and adsorbent (XAD-2 and XAD-2/Sep-Pak C18) techniques, were studied to reveal differences in efficiencies to extract histidine and histidine-related compounds in the urines. Amounts of 'histidine' in concentrates of urine were measured using the bioassay method and a chemical method employing derivatization with fluorescamine. The fluorescamine method also efficiently detected 3-methyl-L-histidine, a product of muscle metabolism excreted in urine, which was found to be unable to support auxotrophic growth in TA1535, leading to exaggerated estimations of the auxotrophic growth enhancing properties of urine extracts. The urine extracts, and pure L-histidine-HCl, were tested using a two-step fluctuation test to estimate auxotrophic growth factor effects in this type of test. Because of a strong dilution effect when adding the histidine-free selection medium, the fluctuation test employed in this study was not found to be particularly sensitive to growth factors. The results of this study indicate that use of a bioassay, employing the same indicator bacteria as the mutagenicity test themselves, is a reliable way to measure histidine-related growth factors in biological samples.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281267", "title": "In vivo fate of MMS-induced DNA lesions that elicit SCE.", "content": "A previously reported in vivo protocol, which uses three-way differential staining (TWD) of sister chromatids, allows the screening of mutagen-induced sister-chromatid exchange (SCE) in each of the two cell divisions after mutagen treatment and also those occurring at apparently the same locus in both divisions. In the present work the effect of methyl methanesulfonate (MMS) was studied by means of this protocol. The results showed that MMS-induced DNA lesions that cause SCE are persistent. Some lesions were induced in the second division, as was inferred from the analysis of the response in single cells. The data also indicate that bromodeoxyuridine reduces DNA sensitivity to SCE induction by MMS.", "contents": "In vivo fate of MMS-induced DNA lesions that elicit SCE. A previously reported in vivo protocol, which uses three-way differential staining (TWD) of sister chromatids, allows the screening of mutagen-induced sister-chromatid exchange (SCE) in each of the two cell divisions after mutagen treatment and also those occurring at apparently the same locus in both divisions. In the present work the effect of methyl methanesulfonate (MMS) was studied by means of this protocol. The results showed that MMS-induced DNA lesions that cause SCE are persistent. Some lesions were induced in the second division, as was inferred from the analysis of the response in single cells. The data also indicate that bromodeoxyuridine reduces DNA sensitivity to SCE induction by MMS."} {"id": "PMID:1281268", "title": "Evaluation of the micronucleus test using a Chinese hamster cell line as an alternative to the conventional in vitro chromosomal aberration test.", "content": "The in vitro micronucleus (MN) test was carried out simultaneously with the conventional chromosomal aberration (CA) test on 11 clastogenic chemicals or spindle poisons with different modes of action using a Chinese hamster cell line (CHL). The method of slide preparation for the MN test was the same as that for the conventional metaphase analysis, except that 1% acetic acid in methanol was used as the cell suspension medium for air-drying (to preserve the cytoplasm around the nucleus). All chemicals tested induced micronuclei reproducibly and dose-dependently in good agreement with the results of metaphase analysis (r = 0.99). Since the MN test methodology is simple and the observation of MN is less subjective than that of CA, we conclude that the in vitro MN test would be a good alternative to the conventional CA test for screening the genotoxicity of chemicals.", "contents": "Evaluation of the micronucleus test using a Chinese hamster cell line as an alternative to the conventional in vitro chromosomal aberration test. The in vitro micronucleus (MN) test was carried out simultaneously with the conventional chromosomal aberration (CA) test on 11 clastogenic chemicals or spindle poisons with different modes of action using a Chinese hamster cell line (CHL). The method of slide preparation for the MN test was the same as that for the conventional metaphase analysis, except that 1% acetic acid in methanol was used as the cell suspension medium for air-drying (to preserve the cytoplasm around the nucleus). All chemicals tested induced micronuclei reproducibly and dose-dependently in good agreement with the results of metaphase analysis (r = 0.99). Since the MN test methodology is simple and the observation of MN is less subjective than that of CA, we conclude that the in vitro MN test would be a good alternative to the conventional CA test for screening the genotoxicity of chemicals."} {"id": "PMID:1281269", "title": "The mouse splenocyte assay, an in vivo/in vitro system for biological monitoring: studies with X-rays, fission neutrons and bleomycin.", "content": "A modified mouse splenocyte culture system was standardized after testing different mitogens (i.e., phytohemagglutinin (PHA), concanavalin A (Con A)). The mitotic index was determined for comparison between different mitogens. Following selection of appropriate mitogen (PHA 16, Flow), a series of experiments were conducted to evaluate the application of a cytokinesis-block for scoring micronuclei and assays for chromosomal aberrations produced by treatment in G0 and G2 for the purposes of biological dosimetry following in vivo and/or in vitro exposure to X-rays, fission neutrons and bleomycin. In the X-irradiation studies, the frequencies of micronuclei and chromosomal aberrations (i.e., dicentrics and rings) increased in a dose-dependent manner. These data could be fitted to a linear-quadratic model. No difference was observed between irradiation in vivo and in vitro, suggesting that measurement of dicentrics and micronuclei in vitro after X-irradiation can be used as an in vivo dosimeter. Following in vivo irradiation with 1 MeV fission neutrons and in vitro culturing of mouse splenocytes, linear dose-response curves were obtained for induction of micronuclei and chromosomal aberrations. The lethal effects of neutrons were shown to be significantly greater than for a similar dose of X-rays. The relative biological effectiveness (RBE) was 6-8 in a dose range of 0.25-3 Gy for radiation-induced asymmetrical exchanges (dicentrics and rings), and about 8 for micronuclei in a dose range of 0.25-2 Gy. Furthermore, the induction of chromosomal aberrations by bleomycin was investigated in mouse G0 splenocytes (in vitro) and compared with X-ray data. Following bleomycin treatment (2 h) a similar pattern of dose-response curve was obtained as with X-rays. In this context a bleomycin rad equivalent of 20 micrograms/ml = 0.50 Gy was estimated.", "contents": "The mouse splenocyte assay, an in vivo/in vitro system for biological monitoring: studies with X-rays, fission neutrons and bleomycin. A modified mouse splenocyte culture system was standardized after testing different mitogens (i.e., phytohemagglutinin (PHA), concanavalin A (Con A)). The mitotic index was determined for comparison between different mitogens. Following selection of appropriate mitogen (PHA 16, Flow), a series of experiments were conducted to evaluate the application of a cytokinesis-block for scoring micronuclei and assays for chromosomal aberrations produced by treatment in G0 and G2 for the purposes of biological dosimetry following in vivo and/or in vitro exposure to X-rays, fission neutrons and bleomycin. In the X-irradiation studies, the frequencies of micronuclei and chromosomal aberrations (i.e., dicentrics and rings) increased in a dose-dependent manner. These data could be fitted to a linear-quadratic model. No difference was observed between irradiation in vivo and in vitro, suggesting that measurement of dicentrics and micronuclei in vitro after X-irradiation can be used as an in vivo dosimeter. Following in vivo irradiation with 1 MeV fission neutrons and in vitro culturing of mouse splenocytes, linear dose-response curves were obtained for induction of micronuclei and chromosomal aberrations. The lethal effects of neutrons were shown to be significantly greater than for a similar dose of X-rays. The relative biological effectiveness (RBE) was 6-8 in a dose range of 0.25-3 Gy for radiation-induced asymmetrical exchanges (dicentrics and rings), and about 8 for micronuclei in a dose range of 0.25-2 Gy. Furthermore, the induction of chromosomal aberrations by bleomycin was investigated in mouse G0 splenocytes (in vitro) and compared with X-ray data. Following bleomycin treatment (2 h) a similar pattern of dose-response curve was obtained as with X-rays. In this context a bleomycin rad equivalent of 20 micrograms/ml = 0.50 Gy was estimated."} {"id": "PMID:1281270", "title": "Schedule dependent variation in human lymphocyte sensitivity to bleomycin and repair of chromosomal aberrations in G2.", "content": "Bleomycin (BLM) induced chromosomal damage in G2 phase and its repair kinetics in normal human lymphocytes were studied following different treatment schedules. As a first step, a dose-response curve was obtained (concentrations of 5-50 micrograms/ml). For repair kinetics studies, blood samples were treated with BLM at a concentration of 20 micrograms/ml. Continuous treatment produced equal numbers of breaks per cell (br/c) when the cells were treated 3, 4 or 5 h before fixation. If the treatment time was extended to 6 h, the level of br/c was increased 2-fold (p < 0.001) as a result of an increased number of cells with more than 3 br/c. The curves obtained after pulse treatment showed maximal chromosome damage at time 3 (45 min BLM treatment, followed by 2 h repair in drug free medium). When the time after treatment was extended to 4 h (treatment time 5), a 50% reduction in chromosome damage was measured. It was found out that at treatment points 3, 4 and 5 the differences in breaks per cell at the different schedules applied were statistically highly significant. If caffeine (CAF) was added, the continuous treatment, BLM+CAF, induced a statistically significant increase in the frequency of br/c at every treatment point, but the shape of the curve illustrating the kinetics of chromosomal damage remained unchanged. Moreover, the addition of CAF at continuous BLM treatment brings the level of br/c close to that measured at the pulse BLM treatment except for treatment time 3. When applied in a combination with BLM, CAF considerably modified the kinetics of chromosome damage for a pulse (BLM alone) treatment. The possible reasons for the changes in the level of br/c as well as a tentative scheme for assessment of chromosome damage repair capacity after BLM treatment are discussed.", "contents": "Schedule dependent variation in human lymphocyte sensitivity to bleomycin and repair of chromosomal aberrations in G2. Bleomycin (BLM) induced chromosomal damage in G2 phase and its repair kinetics in normal human lymphocytes were studied following different treatment schedules. As a first step, a dose-response curve was obtained (concentrations of 5-50 micrograms/ml). For repair kinetics studies, blood samples were treated with BLM at a concentration of 20 micrograms/ml. Continuous treatment produced equal numbers of breaks per cell (br/c) when the cells were treated 3, 4 or 5 h before fixation. If the treatment time was extended to 6 h, the level of br/c was increased 2-fold (p < 0.001) as a result of an increased number of cells with more than 3 br/c. The curves obtained after pulse treatment showed maximal chromosome damage at time 3 (45 min BLM treatment, followed by 2 h repair in drug free medium). When the time after treatment was extended to 4 h (treatment time 5), a 50% reduction in chromosome damage was measured. It was found out that at treatment points 3, 4 and 5 the differences in breaks per cell at the different schedules applied were statistically highly significant. If caffeine (CAF) was added, the continuous treatment, BLM+CAF, induced a statistically significant increase in the frequency of br/c at every treatment point, but the shape of the curve illustrating the kinetics of chromosomal damage remained unchanged. Moreover, the addition of CAF at continuous BLM treatment brings the level of br/c close to that measured at the pulse BLM treatment except for treatment time 3. When applied in a combination with BLM, CAF considerably modified the kinetics of chromosome damage for a pulse (BLM alone) treatment. The possible reasons for the changes in the level of br/c as well as a tentative scheme for assessment of chromosome damage repair capacity after BLM treatment are discussed."} {"id": "PMID:1281271", "title": "Inhibitory activity of heat treated vegetables and indigestible polysaccharides on mutagenicity.", "content": "The effects of heat treated vegetables on mutagenicity were studied using the Salmonella typhimurium system. The mutagens used were 3-amino-1-methyl-5H-pyrido[4,3-b]indole, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, 4-nitroquinoline-1-oxide, acridine yellow and 2-aminoanthracene. Most of the heated vegetables unexpectedly showed greater inhibitory activity against the mutagenicity than unheated samples. The activity was increased markedly by heat treatment of water soluble indigestible polysaccharides (IPS). The increase in inhibitory activity due to heat treatment of IPS coincided well with the decrease in their viscosity. Incubating mixtures of mutagens with heated water soluble IPS decreased their affinity for XAD-2 resin. Heating seems to increase the detoxification ability of dietary fibers.", "contents": "Inhibitory activity of heat treated vegetables and indigestible polysaccharides on mutagenicity. The effects of heat treated vegetables on mutagenicity were studied using the Salmonella typhimurium system. The mutagens used were 3-amino-1-methyl-5H-pyrido[4,3-b]indole, 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide, 4-nitroquinoline-1-oxide, acridine yellow and 2-aminoanthracene. Most of the heated vegetables unexpectedly showed greater inhibitory activity against the mutagenicity than unheated samples. The activity was increased markedly by heat treatment of water soluble indigestible polysaccharides (IPS). The increase in inhibitory activity due to heat treatment of IPS coincided well with the decrease in their viscosity. Incubating mixtures of mutagens with heated water soluble IPS decreased their affinity for XAD-2 resin. Heating seems to increase the detoxification ability of dietary fibers."} {"id": "PMID:1281272", "title": "Genotoxic effects of sodium arsenite on human cells.", "content": "The effects of sodium arsenite (SA) were studied either alone or in combination with X-rays in peripheral blood lymphocytes, and with short-wave ultraviolet (UV) radiation in primary human fibroblast culture systems. It was found that SA (i) inhibited the cell cycle progression of phytohaemagglutinin (PHA)-responsive lymphocytes, (ii) induced chromatid-type aberrations and sister-chromatid exchanges (SCEs) as a function of concentration and (iii) potentiated the X-ray- and UV-induced chromosomal damage. Our results suggest that SA interferes with the DNA repair process, presumably by inhibiting the ligase activity. This accounted for an increase in the DNA replication-dependent processes, chromatid aberrations and SCEs and synergistic enhancement of the X-ray- and UV-induced chromosomal damage. This ability of arsenite may be responsible for its comutagenic properties with different types of mutagens and hence its carcinogenicity.", "contents": "Genotoxic effects of sodium arsenite on human cells. The effects of sodium arsenite (SA) were studied either alone or in combination with X-rays in peripheral blood lymphocytes, and with short-wave ultraviolet (UV) radiation in primary human fibroblast culture systems. It was found that SA (i) inhibited the cell cycle progression of phytohaemagglutinin (PHA)-responsive lymphocytes, (ii) induced chromatid-type aberrations and sister-chromatid exchanges (SCEs) as a function of concentration and (iii) potentiated the X-ray- and UV-induced chromosomal damage. Our results suggest that SA interferes with the DNA repair process, presumably by inhibiting the ligase activity. This accounted for an increase in the DNA replication-dependent processes, chromatid aberrations and SCEs and synergistic enhancement of the X-ray- and UV-induced chromosomal damage. This ability of arsenite may be responsible for its comutagenic properties with different types of mutagens and hence its carcinogenicity."} {"id": "PMID:1281273", "title": "Chronic gamma-irradiation results in increased cell killing and chromosomal aberration with specific breakpoints in fibroblast cell strains derived from non-Hodgkin's lymphoma patients.", "content": "Cultured skin fibroblast cells from 6 patients with non-Hodgkin's lymphoma (NHL) and 2 clinically normal subjects were compared for cell survival and chromosomal aberration after chronic gamma-irradiation. Fibroblasts from an ataxia telangiectasia (AT) homozygote and an AT heterozygote were used as positive controls. Following irradiation, fibroblasts from all 6 NHL patients showed an increase in both cell death and chromosomal aberration (breaks and rearrangements) compared to the normal subjects. The difference in the frequency of chromosomal aberration between the normals and the NHL patients remained virtually unchanged over a period of 24-72 h post irradiation incubation of the cells. Cell cycle analysis by flow cytometry carried out in 1 normal and 1 NHL fibroblast cell strain showed that more cells representing the NHL patient were in G2/M phase compared to the normal at various times of cytogenetic analysis. While the AT homozygote appeared to be the most radiosensitive, the AT heterozygote showed a slightly higher incidence of cell death and chromosomal aberration than the normals. The cellular and chromosomal radiosensitivity of fibroblast cell lines from the NHL patients differed slightly from that of the AT heterozygote but clearly occupied an intermediate position between the AT homozygote and the normal subjects. Cells from 3 of the NHL patients showed radiation-induced specific chromosomal breaks involving chromosomes 1, 2, 6, 8, 10 and 11 which correspond to known fragile sites. Such breakpoints associated with increased radiosensitivity may be indicative of predisposition to malignancy in the patients studied.", "contents": "Chronic gamma-irradiation results in increased cell killing and chromosomal aberration with specific breakpoints in fibroblast cell strains derived from non-Hodgkin's lymphoma patients. Cultured skin fibroblast cells from 6 patients with non-Hodgkin's lymphoma (NHL) and 2 clinically normal subjects were compared for cell survival and chromosomal aberration after chronic gamma-irradiation. Fibroblasts from an ataxia telangiectasia (AT) homozygote and an AT heterozygote were used as positive controls. Following irradiation, fibroblasts from all 6 NHL patients showed an increase in both cell death and chromosomal aberration (breaks and rearrangements) compared to the normal subjects. The difference in the frequency of chromosomal aberration between the normals and the NHL patients remained virtually unchanged over a period of 24-72 h post irradiation incubation of the cells. Cell cycle analysis by flow cytometry carried out in 1 normal and 1 NHL fibroblast cell strain showed that more cells representing the NHL patient were in G2/M phase compared to the normal at various times of cytogenetic analysis. While the AT homozygote appeared to be the most radiosensitive, the AT heterozygote showed a slightly higher incidence of cell death and chromosomal aberration than the normals. The cellular and chromosomal radiosensitivity of fibroblast cell lines from the NHL patients differed slightly from that of the AT heterozygote but clearly occupied an intermediate position between the AT homozygote and the normal subjects. Cells from 3 of the NHL patients showed radiation-induced specific chromosomal breaks involving chromosomes 1, 2, 6, 8, 10 and 11 which correspond to known fragile sites. Such breakpoints associated with increased radiosensitivity may be indicative of predisposition to malignancy in the patients studied."} {"id": "PMID:1281274", "title": "Rat pulmonary microsomal cytochrome P-450 enzymes involved in the activation of procarcinogens.", "content": "Rat lung microsomal cytochrome P-450 (P-450) enzymes have been characterized with regard to their catalytic specificities towards activation of several procarcinogens to genotoxic metabolites in Salmonella typhimurium TA1535/pSK1002. We first examined the roles of rat liver microsomal P-450 enzymes in the activation of benzo[a]pyrene and its 7,8-diol enantiomers to genotoxic products, and found that P-450 1A1 is a major catalyst for the activation of these potential procarcinogens in rat livers. Using lung microsomes isolated from rats treated with various P-450 inducers we obtained evidence that at least three P-450 enzymes are involved in the activation of several procarcinogens. Immunoinhibition studies support the view that benzo[a]pyrene and its 7,8-diol derivatives, other dihydrodiol derivatives of polycyclic aromatic hydrocarbons, and 3-amino-1-methyl-5H-pyrido[4,3-b]indole are activated to genotoxins mainly by rat P-450 1A1, which is inducible in rat lungs by 5,6-benzoflavone and the polychlorinated biphenyl mixture Aroclor 1254. Activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline and 2-amino-3-methylimidazo[4,5-f]quinoline may be catalyzed by another P-450 enzyme because the activities were not induced by treatment with 5,6-benzoflavone or Aroclor 1254. The observation that both activities were inhibited by antibodies raised against P-450 1A2 and by 7,8-benzoflavone suggests a role for an enzyme of P-450 1A family, probably P-450 1A2, in rat lung microsomes. The activation of aflatoxin B1 and sterigmatocystin appears to be catalyzed by other P-450 enzyme(s) rather than the P-450 1A family as judged by the different responses of activities to the P-450 inducers and the specific antibodies in rat lung microsomes. Interestingly, lung microsomal activation of several procarcinogens was found to be suppressed in rats treated with isosafrole and pregnenolone 16 alpha-carbonitrile. Thus, the results support the roles of different P-450 enzymes in the activation of procarcinogens in rat lung microsomes.", "contents": "Rat pulmonary microsomal cytochrome P-450 enzymes involved in the activation of procarcinogens. Rat lung microsomal cytochrome P-450 (P-450) enzymes have been characterized with regard to their catalytic specificities towards activation of several procarcinogens to genotoxic metabolites in Salmonella typhimurium TA1535/pSK1002. We first examined the roles of rat liver microsomal P-450 enzymes in the activation of benzo[a]pyrene and its 7,8-diol enantiomers to genotoxic products, and found that P-450 1A1 is a major catalyst for the activation of these potential procarcinogens in rat livers. Using lung microsomes isolated from rats treated with various P-450 inducers we obtained evidence that at least three P-450 enzymes are involved in the activation of several procarcinogens. Immunoinhibition studies support the view that benzo[a]pyrene and its 7,8-diol derivatives, other dihydrodiol derivatives of polycyclic aromatic hydrocarbons, and 3-amino-1-methyl-5H-pyrido[4,3-b]indole are activated to genotoxins mainly by rat P-450 1A1, which is inducible in rat lungs by 5,6-benzoflavone and the polychlorinated biphenyl mixture Aroclor 1254. Activation of 2-amino-3,5-dimethylimidazo[4,5-f]quinoline and 2-amino-3-methylimidazo[4,5-f]quinoline may be catalyzed by another P-450 enzyme because the activities were not induced by treatment with 5,6-benzoflavone or Aroclor 1254. The observation that both activities were inhibited by antibodies raised against P-450 1A2 and by 7,8-benzoflavone suggests a role for an enzyme of P-450 1A family, probably P-450 1A2, in rat lung microsomes. The activation of aflatoxin B1 and sterigmatocystin appears to be catalyzed by other P-450 enzyme(s) rather than the P-450 1A family as judged by the different responses of activities to the P-450 inducers and the specific antibodies in rat lung microsomes. Interestingly, lung microsomal activation of several procarcinogens was found to be suppressed in rats treated with isosafrole and pregnenolone 16 alpha-carbonitrile. Thus, the results support the roles of different P-450 enzymes in the activation of procarcinogens in rat lung microsomes."} {"id": "PMID:1281275", "title": "Anticlastogenic effect of flavonoids against mutagen-induced micronuclei in mice.", "content": "14 flavonoids, including flavone and flavonol derivatives, were tested for their anticlastogenic effect against induction of micronuclei by benzo[a]pyrene in polychromatic erythrocytes of mice. When each flavonoid was administered orally, together with intraperitoneally administered benzo[a]pyrene, most flavonol derivatives showed an anticlastogenic effect. The data suggest that the 2,3-double bond and 3,5,7-hydroxyl groups in the flavonoid molecules may be essential to produce anticlastogenic effects against benzo[a]pyrene. Galangin, one of the active compounds, and (-)-epicatechin, a weak one, were administered to mice in order to compare their anticlastogenic effect against 3 different kinds of carcinogens: ethyl methanesulfonate, 7,12-dimethylbenz[a]anthracene, and adriamycin. Galangin showed a stronger anticlastogenic effect than (-)-epicatechin against ethyl methanesulfonate and 7,12-dimethylbenz[a]anthracene. However, there was no significant effect against adriamycin-induced micronuclei by both compounds. Our study indicates that most flavonoids are anticlastogenic agents. Their anticlastogenic effects are apparently independent of their own clastogenic activities. Furthermore, their anticlastogenic activities do not apply universally to all types of genotoxic chemicals.", "contents": "Anticlastogenic effect of flavonoids against mutagen-induced micronuclei in mice. 14 flavonoids, including flavone and flavonol derivatives, were tested for their anticlastogenic effect against induction of micronuclei by benzo[a]pyrene in polychromatic erythrocytes of mice. When each flavonoid was administered orally, together with intraperitoneally administered benzo[a]pyrene, most flavonol derivatives showed an anticlastogenic effect. The data suggest that the 2,3-double bond and 3,5,7-hydroxyl groups in the flavonoid molecules may be essential to produce anticlastogenic effects against benzo[a]pyrene. Galangin, one of the active compounds, and (-)-epicatechin, a weak one, were administered to mice in order to compare their anticlastogenic effect against 3 different kinds of carcinogens: ethyl methanesulfonate, 7,12-dimethylbenz[a]anthracene, and adriamycin. Galangin showed a stronger anticlastogenic effect than (-)-epicatechin against ethyl methanesulfonate and 7,12-dimethylbenz[a]anthracene. However, there was no significant effect against adriamycin-induced micronuclei by both compounds. Our study indicates that most flavonoids are anticlastogenic agents. Their anticlastogenic effects are apparently independent of their own clastogenic activities. Furthermore, their anticlastogenic activities do not apply universally to all types of genotoxic chemicals."} {"id": "PMID:1281276", "title": "Effect of inhibitor of poly (ADP-ribose) polymerase in blood lymphocyte cultures of untreated leprosy patients.", "content": "Poly (ADP-ribose) polymerase is a cellular repair enzyme synthesised following damage to DNA. 3-Aminobenzamide (3-AB) is an inhibitor of this repair enzyme. To study repair efficiency in leprosy patients, who usually show a significantly higher frequency of spontaneous chromosome aberrations and sister-chromatid exchanges (SCEs), their blood lymphocyte cultures were treated with 3-AB. A marginal increase in the frequency of chromosome aberrations was observed following treatment with 3-AB in controls as well as in patient groups. There was also no significant difference in the frequency of SCEs in control cultures with or without 3-AB. A significant increase in the frequency of SCEs was observed in lymphocyte cultures of paucibacillary (PB) and multibacillary (MB) patients treated with 3-AB when compared with controls. Observation of a significant increase in the frequency of SCEs in 3-AB-treated cultures over the untreated value indicates that DNA damage caused in leprosy patients following mycobacterial infection is not repaired because of the presence of the inhibitor of repair enzyme.", "contents": "Effect of inhibitor of poly (ADP-ribose) polymerase in blood lymphocyte cultures of untreated leprosy patients. Poly (ADP-ribose) polymerase is a cellular repair enzyme synthesised following damage to DNA. 3-Aminobenzamide (3-AB) is an inhibitor of this repair enzyme. To study repair efficiency in leprosy patients, who usually show a significantly higher frequency of spontaneous chromosome aberrations and sister-chromatid exchanges (SCEs), their blood lymphocyte cultures were treated with 3-AB. A marginal increase in the frequency of chromosome aberrations was observed following treatment with 3-AB in controls as well as in patient groups. There was also no significant difference in the frequency of SCEs in control cultures with or without 3-AB. A significant increase in the frequency of SCEs was observed in lymphocyte cultures of paucibacillary (PB) and multibacillary (MB) patients treated with 3-AB when compared with controls. Observation of a significant increase in the frequency of SCEs in 3-AB-treated cultures over the untreated value indicates that DNA damage caused in leprosy patients following mycobacterial infection is not repaired because of the presence of the inhibitor of repair enzyme."} {"id": "PMID:1281277", "title": "Chromosomal anomalies in radiation-induced fibrosis in the pig.", "content": "R-banded karyotypes were established on fibroblasts from fibrotic tissues derived from experimental fibrosis induced in pigs, either surgically or by 64 Gy of gamma-rays from iridium-192. No chromosome aberrations were observed in the surgical fibrosis. In radiation-induced fibrosis, the high frequency of abnormal karyotypes and the frequent complexity of the chromosomal rearrangements suggest that the fibroblasts originated either from the 64-Gy area, or from the penumbra, but certainly not from non-irradiated areas. At early passages in vitro, almost all karyotypes were different, demonstrating a multiclonal origin of fibrotic tissue. At late passages (above 24), the situation was quite different, with the persistence of one or two clones only, demonstrating a strong selective pressure occurring in vitro.", "contents": "Chromosomal anomalies in radiation-induced fibrosis in the pig. R-banded karyotypes were established on fibroblasts from fibrotic tissues derived from experimental fibrosis induced in pigs, either surgically or by 64 Gy of gamma-rays from iridium-192. No chromosome aberrations were observed in the surgical fibrosis. In radiation-induced fibrosis, the high frequency of abnormal karyotypes and the frequent complexity of the chromosomal rearrangements suggest that the fibroblasts originated either from the 64-Gy area, or from the penumbra, but certainly not from non-irradiated areas. At early passages in vitro, almost all karyotypes were different, demonstrating a multiclonal origin of fibrotic tissue. At late passages (above 24), the situation was quite different, with the persistence of one or two clones only, demonstrating a strong selective pressure occurring in vitro."} {"id": "PMID:1281278", "title": "SV40 T antigen induced chromosomal changes reflect a process that is both clastogenic and aneuploidogenic and is ongoing throughout neoplastic progression of human fibroblasts.", "content": "In human fibroblasts, the expression of SV40 large T antigen is known to cause a variety of chromosomal aberrations and especially dicentric chromosomes. In some cases, the later aberrations have been reported to be reversible telomeric associations. We report here aberration and chromosome number studies of twenty-nine T antigen positive lineages, studied from their initiation by transfection of T antigen sequences into human diploid fibroblasts, until crisis or immortalization occurred or, in some cases until the lines became tumorigenic in nude mice. The data show that T antigen consistently produced chromosomal instability of both number and structure by an active process that began before transformation indicators were positive and continued throughout neoplastic progression. The most frequently observed aberrations were dicentric chromosomes, which were shown to be true dicentrics by examination by in situ hybridization with telomeric sequences. These data are consistent with the hypothesis that T antigen causes human fibroblasts to become neoplastically transformed by successive rounds of chromosomal mutation and lineage evolution.", "contents": "SV40 T antigen induced chromosomal changes reflect a process that is both clastogenic and aneuploidogenic and is ongoing throughout neoplastic progression of human fibroblasts. In human fibroblasts, the expression of SV40 large T antigen is known to cause a variety of chromosomal aberrations and especially dicentric chromosomes. In some cases, the later aberrations have been reported to be reversible telomeric associations. We report here aberration and chromosome number studies of twenty-nine T antigen positive lineages, studied from their initiation by transfection of T antigen sequences into human diploid fibroblasts, until crisis or immortalization occurred or, in some cases until the lines became tumorigenic in nude mice. The data show that T antigen consistently produced chromosomal instability of both number and structure by an active process that began before transformation indicators were positive and continued throughout neoplastic progression. The most frequently observed aberrations were dicentric chromosomes, which were shown to be true dicentrics by examination by in situ hybridization with telomeric sequences. These data are consistent with the hypothesis that T antigen causes human fibroblasts to become neoplastically transformed by successive rounds of chromosomal mutation and lineage evolution."} {"id": "PMID:1281279", "title": "Cellular responses to hematoporphyrin-induced photooxidative damage in Fanconi anemia, xeroderma pigmentosum and normal human fibroblasts.", "content": "Several observations reported in the literature suggest that singlet oxygen (1O2) might play a role in the clastogenic process in Fanconi anemia (FA) cells, and that the antioxidant status of xeroderma pigmentosum (XP) may also be altered. In order to test the ability of FA and XP cells, relative to normal cells, to cope with 1O2 damage, the effects of photosensitization by hematoporphyrin (HP) have been determined (i) on host cell reactivation (HCR) of damaged infecting herpes simplex virus (HSV) or transfecting SV40 DNA, and (ii) on DNA template capability and clonogenicity of treated cells. Results showed no significant difference among the three types of cells, either for the survival of HP-photosensitized HSV, or for the yields of SV40 virus following transfection of cultures with damaged viral DNA. The treatment of cells with HP plus 365-nm light leads to a dose-dependent, homothetic reduction of 18S and 28S ribosomal RNA (rRNA) synthesis, presumably through a mechanism other than the formation of transcription termination sites. After a 24-h post-exposure incubation, the rate of rRNA synthesis was restored to higher than normal levels in all cell lines. Finally, two FA cell lines showed a higher survival to HP photosensitization than two normal cell lines. Another FA cell line and XP-A and XP-C cells were in the range of sensitivity of the two normal strains for this treatment. These results indicate that FA cells possess an antioxidant defense system at least as efficient as that of normal cells for processing 1O2-induced damage.", "contents": "Cellular responses to hematoporphyrin-induced photooxidative damage in Fanconi anemia, xeroderma pigmentosum and normal human fibroblasts. Several observations reported in the literature suggest that singlet oxygen (1O2) might play a role in the clastogenic process in Fanconi anemia (FA) cells, and that the antioxidant status of xeroderma pigmentosum (XP) may also be altered. In order to test the ability of FA and XP cells, relative to normal cells, to cope with 1O2 damage, the effects of photosensitization by hematoporphyrin (HP) have been determined (i) on host cell reactivation (HCR) of damaged infecting herpes simplex virus (HSV) or transfecting SV40 DNA, and (ii) on DNA template capability and clonogenicity of treated cells. Results showed no significant difference among the three types of cells, either for the survival of HP-photosensitized HSV, or for the yields of SV40 virus following transfection of cultures with damaged viral DNA. The treatment of cells with HP plus 365-nm light leads to a dose-dependent, homothetic reduction of 18S and 28S ribosomal RNA (rRNA) synthesis, presumably through a mechanism other than the formation of transcription termination sites. After a 24-h post-exposure incubation, the rate of rRNA synthesis was restored to higher than normal levels in all cell lines. Finally, two FA cell lines showed a higher survival to HP photosensitization than two normal cell lines. Another FA cell line and XP-A and XP-C cells were in the range of sensitivity of the two normal strains for this treatment. These results indicate that FA cells possess an antioxidant defense system at least as efficient as that of normal cells for processing 1O2-induced damage."} {"id": "PMID:1281280", "title": "Heritable alterations at the adenine phosphoribosyltransferase (APRT) locus in human lymphoblastoid cell lines.", "content": "Human lymphoblastoid cell lines derived from WI-L2 exhibit unexpected frequencies of diaminopurine (DAP) resistant mutants. The background mutant fractions of 10(-7) to 10(-8) in untreated cultures are much lower than the frequencies expected for loss of a heterozygous autosomal locus (10(-5) to 10(-6), yet much higher than expected for a homozygous locus (10(-10) to 10(-12). We used aminopterin, adenine and thymidine (AAT) to select DAP-sensitive (DAPS) revertants from one resistant line. The background frequency of DAPR in these revertant cell lines ranged from 3.5 to 6.5 x 10(-4), approximately the square root of 10(-7). Thus these data suggest that both alleles of aprt are inactivated at similarly high frequencies. They also indicate that the DAPS revertants were heterozygotes (aprt +/-) or hemizygotes (aprt +/0) and that WI-L2 was homozygous (aprt+/+). Mutational dose-response studies with X-rays, ethyl methanesulfonate (EMS), and ICR-191 were conducted in 4 of these revertant cell lines. EMS and ICR-191, which induce mainly point mutations, did not induce an increase in mutant fraction. A dose of 200 cGy X-rays, however, induced a frequency of 10(-3). Treatment of DAPR cells with 5-azacytidine induced a significant increase in reversion to DAPS. Southern blot analysis of the aprt gene after digestion with MspI or HpaII also suggests that differential methylation changes may play a major role in the generation of DAP sensitivity and resistance.", "contents": "Heritable alterations at the adenine phosphoribosyltransferase (APRT) locus in human lymphoblastoid cell lines. Human lymphoblastoid cell lines derived from WI-L2 exhibit unexpected frequencies of diaminopurine (DAP) resistant mutants. The background mutant fractions of 10(-7) to 10(-8) in untreated cultures are much lower than the frequencies expected for loss of a heterozygous autosomal locus (10(-5) to 10(-6), yet much higher than expected for a homozygous locus (10(-10) to 10(-12). We used aminopterin, adenine and thymidine (AAT) to select DAP-sensitive (DAPS) revertants from one resistant line. The background frequency of DAPR in these revertant cell lines ranged from 3.5 to 6.5 x 10(-4), approximately the square root of 10(-7). Thus these data suggest that both alleles of aprt are inactivated at similarly high frequencies. They also indicate that the DAPS revertants were heterozygotes (aprt +/-) or hemizygotes (aprt +/0) and that WI-L2 was homozygous (aprt+/+). Mutational dose-response studies with X-rays, ethyl methanesulfonate (EMS), and ICR-191 were conducted in 4 of these revertant cell lines. EMS and ICR-191, which induce mainly point mutations, did not induce an increase in mutant fraction. A dose of 200 cGy X-rays, however, induced a frequency of 10(-3). Treatment of DAPR cells with 5-azacytidine induced a significant increase in reversion to DAPS. Southern blot analysis of the aprt gene after digestion with MspI or HpaII also suggests that differential methylation changes may play a major role in the generation of DAP sensitivity and resistance."} {"id": "PMID:1281281", "title": "Degree of alkylation of macromolecules in vivo from variable exposure.", "content": "Measurements of adducts formed with blood proteins, particularly haemoglobin, are increasingly being used to monitor human exposures to genotoxic chemicals. Information about the relationships between levels of genotoxic chemicals in the environment, e.g., concentration in the air, and levels of protein adducts in the blood is particularly important in setting safety standards and assessing risks. This paper describes the relationships between level of exposure to alkylating agents and level of haemoglobin adducts, considering the zero-order kinetics of the disappearance of these adducts. For comparison the corresponding relationship for adducts to macromolecules subjected to turnover, with first-order kinetics of disappearance, is described. For chemically stable and unstable adducts different exposure situations are considered: acute, chronic, intermittent and varying exposure levels. It is shown how an optimum solution of the problem of establishing the relationship between long-term exposure at varying levels (e.g., in work environments) and adduct level can be reached. Through mathematical derivations, which are given, expressions applicable to various exposure patterns are obtained and presented.", "contents": "Degree of alkylation of macromolecules in vivo from variable exposure. Measurements of adducts formed with blood proteins, particularly haemoglobin, are increasingly being used to monitor human exposures to genotoxic chemicals. Information about the relationships between levels of genotoxic chemicals in the environment, e.g., concentration in the air, and levels of protein adducts in the blood is particularly important in setting safety standards and assessing risks. This paper describes the relationships between level of exposure to alkylating agents and level of haemoglobin adducts, considering the zero-order kinetics of the disappearance of these adducts. For comparison the corresponding relationship for adducts to macromolecules subjected to turnover, with first-order kinetics of disappearance, is described. For chemically stable and unstable adducts different exposure situations are considered: acute, chronic, intermittent and varying exposure levels. It is shown how an optimum solution of the problem of establishing the relationship between long-term exposure at varying levels (e.g., in work environments) and adduct level can be reached. Through mathematical derivations, which are given, expressions applicable to various exposure patterns are obtained and presented."} {"id": "PMID:1281282", "title": "The interaction of the Escherichia coli mutD and mutT pathways in the prevention of A:T-->C:G transversions.", "content": "The Escherichia coli mutT mutator allele produces high frequencies of exclusively A:T-->C:G transversions. This is thought to be caused by a failure to prevent or remove A:G mispairs during DNA replication. The mutD5 mutator allele maps to the dnaQ locus which encodes the epsilon subunit of the DNA polymerase III holoenzyme. This subunit provides 3'-->5' exonuclease, proofreading, activity for removing mispaired nucleotides at the 3' end of the newly synthesized DNA strand. mutD5 has an altered epsilon resulting in reduced levels of proofreading and subsequent high mutation frequencies for all base-pair substitutions. We have analyzed the interaction between mutD5 and mutT-induced A:T-->C:G transversions by measuring reversion frequencies in mutD5 and mutT single mutator strains and mutD5mutT double mutator strains using the well-characterized trpA58 and trpA88 alleles. We find that the double mutator strains produce more A:T-->C:G substitutions than would be expected from simple additivity of the single mutator strains. We interpret this to mean that the two systems, at least in part, do act together to prevent the same mutational intermediate from producing A:T-->C:G transversions. It is estimated that over 90% of the mutT-induced A:G mispairs are corrected by proofreading at the trpA58 site while only about 30% are corrected at trpA88. Reversion frequencies in the mutD5mutT double mutator strains indicate A:G misincorporations occur about 100 x more frequently at trpA58 than at the trpA88 site. Using these and other data we also provide estimations of the fidelity contributions for mutT editing, proofreading and methyl-directed mismatch repair at the two trpA sites for both transversions and the transition that could be scored. In the case of A:T-->C:G transversions, both mutT editing and proofreading make major contributions in error reduction with mismatch repair playing a small or no role at all. For the A:T-->G:C transition, proofreading and mismatch repair were both important in preventing mutations while no contribution was observed for mutT editing.", "contents": "The interaction of the Escherichia coli mutD and mutT pathways in the prevention of A:T-->C:G transversions. The Escherichia coli mutT mutator allele produces high frequencies of exclusively A:T-->C:G transversions. This is thought to be caused by a failure to prevent or remove A:G mispairs during DNA replication. The mutD5 mutator allele maps to the dnaQ locus which encodes the epsilon subunit of the DNA polymerase III holoenzyme. This subunit provides 3'-->5' exonuclease, proofreading, activity for removing mispaired nucleotides at the 3' end of the newly synthesized DNA strand. mutD5 has an altered epsilon resulting in reduced levels of proofreading and subsequent high mutation frequencies for all base-pair substitutions. We have analyzed the interaction between mutD5 and mutT-induced A:T-->C:G transversions by measuring reversion frequencies in mutD5 and mutT single mutator strains and mutD5mutT double mutator strains using the well-characterized trpA58 and trpA88 alleles. We find that the double mutator strains produce more A:T-->C:G substitutions than would be expected from simple additivity of the single mutator strains. We interpret this to mean that the two systems, at least in part, do act together to prevent the same mutational intermediate from producing A:T-->C:G transversions. It is estimated that over 90% of the mutT-induced A:G mispairs are corrected by proofreading at the trpA58 site while only about 30% are corrected at trpA88. Reversion frequencies in the mutD5mutT double mutator strains indicate A:G misincorporations occur about 100 x more frequently at trpA58 than at the trpA88 site. Using these and other data we also provide estimations of the fidelity contributions for mutT editing, proofreading and methyl-directed mismatch repair at the two trpA sites for both transversions and the transition that could be scored. In the case of A:T-->C:G transversions, both mutT editing and proofreading make major contributions in error reduction with mismatch repair playing a small or no role at all. For the A:T-->G:C transition, proofreading and mismatch repair were both important in preventing mutations while no contribution was observed for mutT editing."} {"id": "PMID:1281283", "title": "Effect of cis-located human satellite DNA on the electroporation efficiency of neo and HSV-1 tk containing plasmids.", "content": "Highly repetitive satellite DNAs comprise a significant portion of higher eukaryotic genomes and have been implicated in a variety of chromosome processes, such as centromere structure and function, that are related to their presence in heterochromatin. In addition, heterochromatin can induce metastable expression of adjacent genes. However, the role of highly repetitive satellite DNAs in these effects remains to be elucidated. In an effort to address this question, plasmids containing a human 1797-bp EcoRI satellite II DNA, plus the neo and the HSV-1 tk genes, were electroporated into a TK-/NEO- human cell line. The presence of the satellite DNA sequences within the electroporated plasmids was found to interfere with the generation of stable TK+, but not NEO+, transfectants depending on the location and/or orientation of the cloned satellite DNA.", "contents": "Effect of cis-located human satellite DNA on the electroporation efficiency of neo and HSV-1 tk containing plasmids. Highly repetitive satellite DNAs comprise a significant portion of higher eukaryotic genomes and have been implicated in a variety of chromosome processes, such as centromere structure and function, that are related to their presence in heterochromatin. In addition, heterochromatin can induce metastable expression of adjacent genes. However, the role of highly repetitive satellite DNAs in these effects remains to be elucidated. In an effort to address this question, plasmids containing a human 1797-bp EcoRI satellite II DNA, plus the neo and the HSV-1 tk genes, were electroporated into a TK-/NEO- human cell line. The presence of the satellite DNA sequences within the electroporated plasmids was found to interfere with the generation of stable TK+, but not NEO+, transfectants depending on the location and/or orientation of the cloned satellite DNA."} {"id": "PMID:1281285", "title": "CD1b restricts the response of human CD4-8- T lymphocytes to a microbial antigen.", "content": "Molecules encoded by the human CD1 locus on chromosome 1 (ref. 33) are recognized by selected CD4-8- T-cell clones expressing either alpha beta or gamma delta T-cell antigen receptors. The known structural resemblance of CD1 molecules to antigen-presenting molecules encoded by major histocompatibility complex (MHC) genes on human chromosome 6 (refs 3, 4, 34, 35), suggested that CD1 may represent a family of antigen-presenting molecules separate from those encoded in the MHC. Here we report that the proliferative and cytotoxic responses of human CD4-8- alpha beta TCR+ T cells specific for Mycobacterium tuberculosis can be restricted by CD1b, one of the four identified protein products of the CD1 locus. The responses of these T cells to M. tuberculosis seemed not to involve MHC encoded molecules, but were absolutely dependent on the expression of CD1b by the antigen-presenting cell and involved an antigen processing requirement similar to that seen in MHC class II-restricted antigen presentation. These results provide, to our knowledge, the first direct evidence for the proposed antigen-presenting function of CD1 molecules and suggest that the CD1 family plays a role in cell-mediated immunity to microbial pathogens.", "contents": "CD1b restricts the response of human CD4-8- T lymphocytes to a microbial antigen. Molecules encoded by the human CD1 locus on chromosome 1 (ref. 33) are recognized by selected CD4-8- T-cell clones expressing either alpha beta or gamma delta T-cell antigen receptors. The known structural resemblance of CD1 molecules to antigen-presenting molecules encoded by major histocompatibility complex (MHC) genes on human chromosome 6 (refs 3, 4, 34, 35), suggested that CD1 may represent a family of antigen-presenting molecules separate from those encoded in the MHC. Here we report that the proliferative and cytotoxic responses of human CD4-8- alpha beta TCR+ T cells specific for Mycobacterium tuberculosis can be restricted by CD1b, one of the four identified protein products of the CD1 locus. The responses of these T cells to M. tuberculosis seemed not to involve MHC encoded molecules, but were absolutely dependent on the expression of CD1b by the antigen-presenting cell and involved an antigen processing requirement similar to that seen in MHC class II-restricted antigen presentation. These results provide, to our knowledge, the first direct evidence for the proposed antigen-presenting function of CD1 molecules and suggest that the CD1 family plays a role in cell-mediated immunity to microbial pathogens."} {"id": "PMID:1281287", "title": "[Retarded motor and cognitive development of young children with severe kidney disorders].", "content": "Medical and technical advances make it possible to treat young children with end-stage renal disease with far-reaching methods such as continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis (HD). We investigated whether chronic renal failure has deleterious effects on motor function and cognitive development. The pediatric dialysis centres of the university hospitals of Nijmegen, Utrecht and Rotterdam. Prospective study. 18 patients (mean age 37 months) with chronic renal failure since infancy and 18 healthy children (mean age 35 months) as controls were assessed on cognitive and behavioural parameters. Nine patients and 17 control subjects were tested on their motor function. A significant delay (more than one SD) was found in the motor as well as in the cognitive development of the patient group. Within this group a large difference was noticed between patients under conservative treatment (n = 8; mean dev. index 92.0) and those under CAPD or HD treatment (n = 10; mean dev. index 72.4). Young dialysis patients are evidently at risk for developmental retardation. Monitoring this vulnerable group by developmental screening and intensive counselling of the parents is strongly recommended.", "contents": "[Retarded motor and cognitive development of young children with severe kidney disorders]. Medical and technical advances make it possible to treat young children with end-stage renal disease with far-reaching methods such as continuous ambulatory peritoneal dialysis (CAPD) and haemodialysis (HD). We investigated whether chronic renal failure has deleterious effects on motor function and cognitive development. The pediatric dialysis centres of the university hospitals of Nijmegen, Utrecht and Rotterdam. Prospective study. 18 patients (mean age 37 months) with chronic renal failure since infancy and 18 healthy children (mean age 35 months) as controls were assessed on cognitive and behavioural parameters. Nine patients and 17 control subjects were tested on their motor function. A significant delay (more than one SD) was found in the motor as well as in the cognitive development of the patient group. Within this group a large difference was noticed between patients under conservative treatment (n = 8; mean dev. index 92.0) and those under CAPD or HD treatment (n = 10; mean dev. index 72.4). Young dialysis patients are evidently at risk for developmental retardation. Monitoring this vulnerable group by developmental screening and intensive counselling of the parents is strongly recommended."} {"id": "PMID:1281288", "title": "Synthetic amyloid beta-protein fails to produce specific neurotoxicity in monkey cerebral cortex.", "content": "Because progressive amyloid beta-protein (A beta P) deposition and surrounding neuritic dystrophy occur spontaneously in primates, we evaluated the in vivo effects of synthetic A beta P in monkey cortex. Experimental and control A beta P were stereotactically injected into multiple neocortical sites of adult rhesus monkeys in a vehicle of either artificial cerebrospinal fluid or acetonitrile. After 2 weeks or 3 months, injection sites were identified and characterized histologically and immunocytochemically. A beta P antibodies specifically detected the injected A beta P1-40 peptide. Serial sections stained with silver and antineurofilament protein demonstrated comparable degrees of degenerating neurons, dystrophic neurites, and axonal spheroids associated with both experimental and control peptide injections. Alz 50 staining was sparse or absent in all sites. We conclude that specific cellular changes closely resembling AD pathology were not detected in these experiments, and that control and experimental A beta P peptides produced indistinguishable effects. Methodological concerns regarding the in vivo modeling of A beta P bioactivity are discussed.", "contents": "Synthetic amyloid beta-protein fails to produce specific neurotoxicity in monkey cerebral cortex. Because progressive amyloid beta-protein (A beta P) deposition and surrounding neuritic dystrophy occur spontaneously in primates, we evaluated the in vivo effects of synthetic A beta P in monkey cortex. Experimental and control A beta P were stereotactically injected into multiple neocortical sites of adult rhesus monkeys in a vehicle of either artificial cerebrospinal fluid or acetonitrile. After 2 weeks or 3 months, injection sites were identified and characterized histologically and immunocytochemically. A beta P antibodies specifically detected the injected A beta P1-40 peptide. Serial sections stained with silver and antineurofilament protein demonstrated comparable degrees of degenerating neurons, dystrophic neurites, and axonal spheroids associated with both experimental and control peptide injections. Alz 50 staining was sparse or absent in all sites. We conclude that specific cellular changes closely resembling AD pathology were not detected in these experiments, and that control and experimental A beta P peptides produced indistinguishable effects. Methodological concerns regarding the in vivo modeling of A beta P bioactivity are discussed."} {"id": "PMID:1281289", "title": "Intracerebral beta-amyloid(25-35) produces tissue damage: is it neurotoxic?", "content": "beta-Amyloid (1-40) and (25-35) have been reported to be toxic to primary cultured neurons. beta-Amyloid (1-40) was also reported to induce neurodegeneration following intracerebral injection. We attempted to replicate and extend these findings by injecting both the full length amyloid peptide and the 25-35 fragment. beta 1-40 (3 nmol in 1 microliter) or beta 25-35 (20 nmol in 2 microliters) in a vehicle of 10% DMSO (3 and 10 mM concentration, respectively) induced tissue loss and neurodegeneration. We also attempted to prevent the amyloid-induced damage by coinjecting 200 nmol of Substance P. There was no obvious reduction in the size of the lesions. Other studies, however, have reported antagonism of amyloid toxicity with tachykinin agonists. Since beta-amyloid does not appear to bind to tachykinin receptors, there is some question as to the site of the putative interaction of these peptides and, therefore, the mechanism by which beta-amyloid induces tissue damage. Our own results and published cell culture toxicity studies suggest that aggregation of the peptide and physical displacement of tissue may be responsible for both the neuronal and tissue loss, although this hypothesis is not consistent with other published findings.", "contents": "Intracerebral beta-amyloid(25-35) produces tissue damage: is it neurotoxic? beta-Amyloid (1-40) and (25-35) have been reported to be toxic to primary cultured neurons. beta-Amyloid (1-40) was also reported to induce neurodegeneration following intracerebral injection. We attempted to replicate and extend these findings by injecting both the full length amyloid peptide and the 25-35 fragment. beta 1-40 (3 nmol in 1 microliter) or beta 25-35 (20 nmol in 2 microliters) in a vehicle of 10% DMSO (3 and 10 mM concentration, respectively) induced tissue loss and neurodegeneration. We also attempted to prevent the amyloid-induced damage by coinjecting 200 nmol of Substance P. There was no obvious reduction in the size of the lesions. Other studies, however, have reported antagonism of amyloid toxicity with tachykinin agonists. Since beta-amyloid does not appear to bind to tachykinin receptors, there is some question as to the site of the putative interaction of these peptides and, therefore, the mechanism by which beta-amyloid induces tissue damage. Our own results and published cell culture toxicity studies suggest that aggregation of the peptide and physical displacement of tissue may be responsible for both the neuronal and tissue loss, although this hypothesis is not consistent with other published findings."} {"id": "PMID:1281291", "title": "The presence of 17K Mr protein, a major specific substrate for kinase C, found in the triton-insoluble fraction of synaptosome prepared from rat brain.", "content": "Cytoskeletal preparation obtained from synaptosome fractions of rat cerebrum contained the activity of kinase C, which phosphorylated 17K Mr protein endogenous to the preparation. The kinase C activity associated with the synaptosome cytoskeletons is greater in the cerebellum and hippocampus than in the cerebrum. The enhancement rates of phosphorylation of the 17K Mr protein were 293%, 544%, and 526% in the Triton X-100-insoluble fractions of synaptosomes prepared from cerebral cortex, hippocampus, and cerebellum, respectively. The 17K Mr protein was distinct from myelin basic protein (MBP) for the following reasons: 1) The electrophoretic mobility of the protein was slightly smaller than that of major MBP of rat in the polyacrylamide gel of 10-20% linear gradient, and the protein was not contained in the purified rat myelin. 2) The isoelectric point of the protein was in neutral range, whereas that of MBP was in alkaline one. 3) The 17K Mr protein did not cross-react with anti-MBP antibody. The protein was shown to be a major substrate contained in the cytoskeletal preparation of synaptosome obtained from cerebrum except for contaminating MBP. Only serine residue of the 17K Mr protein was phosphorylated by the kinase C endogenous to the preparation. The results suggest strongly that the synaptic role of protein kinase C through phosphorylation of the 17K Mr protein.", "contents": "The presence of 17K Mr protein, a major specific substrate for kinase C, found in the triton-insoluble fraction of synaptosome prepared from rat brain. Cytoskeletal preparation obtained from synaptosome fractions of rat cerebrum contained the activity of kinase C, which phosphorylated 17K Mr protein endogenous to the preparation. The kinase C activity associated with the synaptosome cytoskeletons is greater in the cerebellum and hippocampus than in the cerebrum. The enhancement rates of phosphorylation of the 17K Mr protein were 293%, 544%, and 526% in the Triton X-100-insoluble fractions of synaptosomes prepared from cerebral cortex, hippocampus, and cerebellum, respectively. The 17K Mr protein was distinct from myelin basic protein (MBP) for the following reasons: 1) The electrophoretic mobility of the protein was slightly smaller than that of major MBP of rat in the polyacrylamide gel of 10-20% linear gradient, and the protein was not contained in the purified rat myelin. 2) The isoelectric point of the protein was in neutral range, whereas that of MBP was in alkaline one. 3) The 17K Mr protein did not cross-react with anti-MBP antibody. The protein was shown to be a major substrate contained in the cytoskeletal preparation of synaptosome obtained from cerebrum except for contaminating MBP. Only serine residue of the 17K Mr protein was phosphorylated by the kinase C endogenous to the preparation. The results suggest strongly that the synaptic role of protein kinase C through phosphorylation of the 17K Mr protein."} {"id": "PMID:1281292", "title": "Influence of exogenous gangliosides on the three-dimensional sprouting of goldfish retinal explants in vitro.", "content": "To investigate the 3-dimensional outgrowth of ganglion cells of normal and regenerating goldfish retina, retinal explants were cultured in a serum free 3-D fibrin matrix. Daily applications of exogenous gangliosides (GM1), injected either intraocularly (i.o.) or intraperitoneally (i.p.) had no significant effect on the sprouting activity of retinal explants prepared from lesion-activated goldfish whose corresponding optic nerve had been transected. However, in normal, unlesioned animals, a local i.o. injection of GM1 or mixed gangliosides led to a significant enhancement of the basal retinal sprouting activity as compared to controls, which were injected with a 0.9% NaCl solution. This ganglioside related stimulation was maximal after i.o. injection of low concentrations (3 micrograms/eye), didn't occur at high concentrations (30 micrograms/eye) and was similar to the response obtained after i.o. injection of NGF or insulin. I.o. injected phospholipids had no or a slightly inhibitory effect on the sprouting activity as compared to NaCl controls. Daily in vivo i.o. injections of the monoclonal antibody Q211, specifically recognizing c-pathway polysialogangliosides, led to a dose dependent inhibition of the in vitro sprouting of goldfish retina explants. In summary, these data suggest an involvement of gangliosides in the complex process of induction of neuronal sprouting.", "contents": "Influence of exogenous gangliosides on the three-dimensional sprouting of goldfish retinal explants in vitro. To investigate the 3-dimensional outgrowth of ganglion cells of normal and regenerating goldfish retina, retinal explants were cultured in a serum free 3-D fibrin matrix. Daily applications of exogenous gangliosides (GM1), injected either intraocularly (i.o.) or intraperitoneally (i.p.) had no significant effect on the sprouting activity of retinal explants prepared from lesion-activated goldfish whose corresponding optic nerve had been transected. However, in normal, unlesioned animals, a local i.o. injection of GM1 or mixed gangliosides led to a significant enhancement of the basal retinal sprouting activity as compared to controls, which were injected with a 0.9% NaCl solution. This ganglioside related stimulation was maximal after i.o. injection of low concentrations (3 micrograms/eye), didn't occur at high concentrations (30 micrograms/eye) and was similar to the response obtained after i.o. injection of NGF or insulin. I.o. injected phospholipids had no or a slightly inhibitory effect on the sprouting activity as compared to NaCl controls. Daily in vivo i.o. injections of the monoclonal antibody Q211, specifically recognizing c-pathway polysialogangliosides, led to a dose dependent inhibition of the in vitro sprouting of goldfish retina explants. In summary, these data suggest an involvement of gangliosides in the complex process of induction of neuronal sprouting."} {"id": "PMID:1281290", "title": "beta-Amyloid peptide in vitro toxicity: lot-to-lot variability.", "content": "beta A4 peptide (beta AP) accumulates in amyloid plaques of Alzheimer's disease and may contribute to neuronal degeneration. Conflicting observations have been reported regarding the direct in vitro and in vivo neurotoxicity of beta AP. We have assessed in vitro beta AP toxicity in high density primary rat hippocampal cultures and found marked lot-to-lot differences in the neurotoxic properties of beta AP. One lot of beta AP from a commercial supplier resulted in significant direct neurotoxicity at 10 microM, while 2 other lots from the same supplier were essentially nontoxic. Three additional lots of beta AP from unrelated sources were also nontoxic at 10 microM. Initial biochemical characterization has not yet revealed any marked differences among the various lots of beta AP. Low levels of endotoxin (ca., 1 EU/ml) were detected in several beta AP preparations but did not correlate with neurotoxicity. Our observation that lot-to-lot variability of beta AP occurred even under identical in vitro culture conditions may account for part of the present controversy in this area.", "contents": "beta-Amyloid peptide in vitro toxicity: lot-to-lot variability. beta A4 peptide (beta AP) accumulates in amyloid plaques of Alzheimer's disease and may contribute to neuronal degeneration. Conflicting observations have been reported regarding the direct in vitro and in vivo neurotoxicity of beta AP. We have assessed in vitro beta AP toxicity in high density primary rat hippocampal cultures and found marked lot-to-lot differences in the neurotoxic properties of beta AP. One lot of beta AP from a commercial supplier resulted in significant direct neurotoxicity at 10 microM, while 2 other lots from the same supplier were essentially nontoxic. Three additional lots of beta AP from unrelated sources were also nontoxic at 10 microM. Initial biochemical characterization has not yet revealed any marked differences among the various lots of beta AP. Low levels of endotoxin (ca., 1 EU/ml) were detected in several beta AP preparations but did not correlate with neurotoxicity. Our observation that lot-to-lot variability of beta AP occurred even under identical in vitro culture conditions may account for part of the present controversy in this area."} {"id": "PMID:1281293", "title": "Susceptibility of myelin proteins to a neutral endoproteinase: the degradation of myelin basic protein (MBP) and P2 protein by purified bovine brain multicatalytic proteinase complex (MPC).", "content": "Multicatalytic proteinase complex (MPC) was isolated from bovine brain and the susceptibility of myelin basic protein (MBP) and P2 protein of bovine central and peripheral nervous system was examined. SDS-polyacrylamide electrophoretic analysis of purified MPC revealed protein bands of molecular weight ranging from 22-35 kDa. The enzyme is activated by SDS at a concentration less than 0.01%. Upon incubation with MPC, purified MBP and P2 proteins were degraded into smaller fragments. There was a 57% and 100% loss of MBP at 2 and 6 hours of incubation. The P2 protein which is not susceptible to any endogenous non-lysosomal enzyme thus far studied was digested into small peptide fragments only in the presence of SDS (0.01%) and not in its absence. These results indicate that MPC which is active at physiological conditions may have a role in the turnover of myelin proteins and in demyelinating diseases.", "contents": "Susceptibility of myelin proteins to a neutral endoproteinase: the degradation of myelin basic protein (MBP) and P2 protein by purified bovine brain multicatalytic proteinase complex (MPC). Multicatalytic proteinase complex (MPC) was isolated from bovine brain and the susceptibility of myelin basic protein (MBP) and P2 protein of bovine central and peripheral nervous system was examined. SDS-polyacrylamide electrophoretic analysis of purified MPC revealed protein bands of molecular weight ranging from 22-35 kDa. The enzyme is activated by SDS at a concentration less than 0.01%. Upon incubation with MPC, purified MBP and P2 proteins were degraded into smaller fragments. There was a 57% and 100% loss of MBP at 2 and 6 hours of incubation. The P2 protein which is not susceptible to any endogenous non-lysosomal enzyme thus far studied was digested into small peptide fragments only in the presence of SDS (0.01%) and not in its absence. These results indicate that MPC which is active at physiological conditions may have a role in the turnover of myelin proteins and in demyelinating diseases."} {"id": "PMID:1281295", "title": "[Evaluation of NOR changes in patients with chronic active hepatitis treated with IFN and untreated].", "content": "The Authors consider 30 patients with ECA; 15 of these were treated with IFN and 15 were not treated. The Authors think that the statistically significant difference between patient groups, is a parameter of the pharmacological effects on the horx.", "contents": "[Evaluation of NOR changes in patients with chronic active hepatitis treated with IFN and untreated]. The Authors consider 30 patients with ECA; 15 of these were treated with IFN and 15 were not treated. The Authors think that the statistically significant difference between patient groups, is a parameter of the pharmacological effects on the horx."} {"id": "PMID:1281296", "title": "[Primary non-Hodgkin's lymphoma of paranasal sinuses. Review of the literature and a case report].", "content": "A case of primary extranodal non-Hodgkin's lymphoma arising in paranasal sinuses, in an 89 year-old woman is reported. Histologically it was lymphoplasmacytoid, pleomorphic, diffuse, at intermediate grade of malignancy according to \"Working formulation for clinical usage\" in I EB stage. Complete resolution was obtained with polychemotherapy according to the scheme ProMACE-CytaBOM. After a wide review of the literature, the Authors emphasize incidence, prevalence, clinical symptoms (especially local), the different beginning points, prognostic and therapeutic factors, and the most frequent associations with other illnesses. Agreeing with other Authors, the necessity of using aggressive polychemotherapy is stressed, also in elderly patients, even if at the beginning of the illness.", "contents": "[Primary non-Hodgkin's lymphoma of paranasal sinuses. Review of the literature and a case report]. A case of primary extranodal non-Hodgkin's lymphoma arising in paranasal sinuses, in an 89 year-old woman is reported. Histologically it was lymphoplasmacytoid, pleomorphic, diffuse, at intermediate grade of malignancy according to \"Working formulation for clinical usage\" in I EB stage. Complete resolution was obtained with polychemotherapy according to the scheme ProMACE-CytaBOM. After a wide review of the literature, the Authors emphasize incidence, prevalence, clinical symptoms (especially local), the different beginning points, prognostic and therapeutic factors, and the most frequent associations with other illnesses. Agreeing with other Authors, the necessity of using aggressive polychemotherapy is stressed, also in elderly patients, even if at the beginning of the illness."} {"id": "PMID:1281297", "title": "[Effects of long-term iloprost therapy on Raynaud's phenomenon in progressive systemic sclerosis].", "content": "One of the most appealing current pathogenetic concepts is that progressive systemic sclerosis (PSS) is a reaction to repeated episodes of endothelial cell injury. Injury of small arteries and capillary endothelium initiates reactions which involve increased permeability of the vessels, platelet adherence, myointimal cell proliferation, luminal narrowing and heightened sensitivity of the vessel wall. Clinical evidence of the vessel damage is Raynaud's phenomenon, involving both skin and viscera. The Authors evaluated the effects of iloprost on Raynaud's phenomenon in patients with PSS. This drug provides prolonged vasodilation, reduces platelet aggregation and promotes endothelial lining function repair. This last pattern is of primary importance because it may stop the vicious circle: endothelial injury-platelet hyperaggregation-microangiospasm. Five females were recruited, aged 41-66 years, suffering from well-documented (ARA criteria) PSS, associated with typical Raynaud's phenomenon. The trial provided for intravenous infusion of iloprost at a rate of 1-2 ng/kg/min. First treatment consisted of six-hour infusions on six successive days. After this first treatment, weekly infusions during the winter months were carried on. Drug effectiveness was considered through subjective and objective parameters. All patients showed prominent reduction of number, duration and severity of attacks of Raynaud's phenomenon, improvement of prehensile strength, healing of finger ulcerations and improvement or normalization of digital photoplethysmography. So far, the treatment has been prolonged for years in our patients and still goes on. The side effects of iloprost (headache, flushing, nausea) have been very poor. Therefore, iloprost proved to be a valid drug in the management of Raynaud's phenomenon in patients with PSS, but the inconvenience of intravenous administration may limit its routine use.", "contents": "[Effects of long-term iloprost therapy on Raynaud's phenomenon in progressive systemic sclerosis]. One of the most appealing current pathogenetic concepts is that progressive systemic sclerosis (PSS) is a reaction to repeated episodes of endothelial cell injury. Injury of small arteries and capillary endothelium initiates reactions which involve increased permeability of the vessels, platelet adherence, myointimal cell proliferation, luminal narrowing and heightened sensitivity of the vessel wall. Clinical evidence of the vessel damage is Raynaud's phenomenon, involving both skin and viscera. The Authors evaluated the effects of iloprost on Raynaud's phenomenon in patients with PSS. This drug provides prolonged vasodilation, reduces platelet aggregation and promotes endothelial lining function repair. This last pattern is of primary importance because it may stop the vicious circle: endothelial injury-platelet hyperaggregation-microangiospasm. Five females were recruited, aged 41-66 years, suffering from well-documented (ARA criteria) PSS, associated with typical Raynaud's phenomenon. The trial provided for intravenous infusion of iloprost at a rate of 1-2 ng/kg/min. First treatment consisted of six-hour infusions on six successive days. After this first treatment, weekly infusions during the winter months were carried on. Drug effectiveness was considered through subjective and objective parameters. All patients showed prominent reduction of number, duration and severity of attacks of Raynaud's phenomenon, improvement of prehensile strength, healing of finger ulcerations and improvement or normalization of digital photoplethysmography. So far, the treatment has been prolonged for years in our patients and still goes on. The side effects of iloprost (headache, flushing, nausea) have been very poor. Therefore, iloprost proved to be a valid drug in the management of Raynaud's phenomenon in patients with PSS, but the inconvenience of intravenous administration may limit its routine use."} {"id": "PMID:1281298", "title": "Demonstration of transganglionically transported choleragenoid in rat spinal cord by immunofluorescence cytochemistry.", "content": "Injections of the B-subunit of cholera toxin (CTB) were made into the sciatic nerve of the rat. Following a survival of 2-3 days, the fluorescent antibody technique was used to show that CTB can be utilized as a highly sensitive immunocytochemically detectable transganglionic tracer for primary afferent fibers in the spinal cord. CTB-labeled fibers as well as fibers containing calcitonin gene-related peptide- (CGRP-) or substance P-like immunoreactivity were visualized simultaneously by using different fluorochromes. However, no double labeled fibers were found.", "contents": "Demonstration of transganglionically transported choleragenoid in rat spinal cord by immunofluorescence cytochemistry. Injections of the B-subunit of cholera toxin (CTB) were made into the sciatic nerve of the rat. Following a survival of 2-3 days, the fluorescent antibody technique was used to show that CTB can be utilized as a highly sensitive immunocytochemically detectable transganglionic tracer for primary afferent fibers in the spinal cord. CTB-labeled fibers as well as fibers containing calcitonin gene-related peptide- (CGRP-) or substance P-like immunoreactivity were visualized simultaneously by using different fluorochromes. However, no double labeled fibers were found."} {"id": "PMID:1281299", "title": "Blockade of nitric oxide synthase inhibits nerve-mediated contraction in the rat small intestine.", "content": "Inhibitors of nitric oxide (NO) synthase inhibit nerve-mediated non-adrenergic, non-cholinergic (NANC) smooth muscle relaxation in the gastrointestinal tract. In this study, the effect of a NO synthase inhibitor, NG-nitro-L-arginine, was examined on the tetrodotoxin-sensitive NANC contractile response of the rat isolated ileal myenteric plexus-longitudinal muscle evoked by electrical field stimulation. This contraction was concentration-dependently inhibited by NG-nitro-L-arginine (1-3 x 10(-5) M). The inhibition was partly or entirely reversed by L-arginine. The NO synthase inhibitor did not exhibit any non-specific smooth-muscle depressant action or local anaesthetic effect. Sodium nitroprusside, a putative donor of NO also caused a transient contraction of the rat ileal strip. This response was resistant to tetrodotoxin. It is concluded that an NO synthase product is involved in the mechanism of the nerve-mediated NANC primary contraction due to field stimulation in the rat small intestine.", "contents": "Blockade of nitric oxide synthase inhibits nerve-mediated contraction in the rat small intestine. Inhibitors of nitric oxide (NO) synthase inhibit nerve-mediated non-adrenergic, non-cholinergic (NANC) smooth muscle relaxation in the gastrointestinal tract. In this study, the effect of a NO synthase inhibitor, NG-nitro-L-arginine, was examined on the tetrodotoxin-sensitive NANC contractile response of the rat isolated ileal myenteric plexus-longitudinal muscle evoked by electrical field stimulation. This contraction was concentration-dependently inhibited by NG-nitro-L-arginine (1-3 x 10(-5) M). The inhibition was partly or entirely reversed by L-arginine. The NO synthase inhibitor did not exhibit any non-specific smooth-muscle depressant action or local anaesthetic effect. Sodium nitroprusside, a putative donor of NO also caused a transient contraction of the rat ileal strip. This response was resistant to tetrodotoxin. It is concluded that an NO synthase product is involved in the mechanism of the nerve-mediated NANC primary contraction due to field stimulation in the rat small intestine."} {"id": "PMID:1281300", "title": "Corticotropin releasing factor and galanin-containing neurons projecting to the median eminence of the rat.", "content": "To identify corticotropin releasing factor (CRF)- and galanin (GAL)-containing neurons projecting to the median eminence, a retrograde tracing method with True blue was combined with a double-staining method. It was demonstrated that some True blue-labeled CRF neurons in the paraventricular nucleus were also immunoreactive for GAL. These findings support the hypothesis that GAL and CRF are simultaneously involved in regulation of ACTH secretion from the anterior pituitary.", "contents": "Corticotropin releasing factor and galanin-containing neurons projecting to the median eminence of the rat. To identify corticotropin releasing factor (CRF)- and galanin (GAL)-containing neurons projecting to the median eminence, a retrograde tracing method with True blue was combined with a double-staining method. It was demonstrated that some True blue-labeled CRF neurons in the paraventricular nucleus were also immunoreactive for GAL. These findings support the hypothesis that GAL and CRF are simultaneously involved in regulation of ACTH secretion from the anterior pituitary."} {"id": "PMID:1281301", "title": "An evaluation of dietary guidance graphic alternatives: the evolution of the eating right pyramid.", "content": "The pyramid graphic was found to be most effective in conveying the messages of moderation and proportionality. The pyramid design might be further strengthened in conveying the total moderation message by including both FOS pictures and symbols in the same graphic. The pyramid also has considerable strength in promoting the message of variety. More important, the pyramid graphic did not convey misinformation about variety, proportionality, and moderation or about the importance of consuming foods in adequate amounts from all the major food groups to achieve a healthful diet. The bowl design was found to be far less effective in promoting the moderation and proportionality messages, but did illustrate the variety message somewhat better than the pyramid. Although respondents indicated a preference for the bowel shape, it is important to note that even in the groups where preference for the bowl was the strongest (i.e., younger, less educated, ethnic minority, and low-income respondents), the pyramid was more likely to be identified as the graphic that suggested the moderation-of-fat message most clearly. Further, preference for the bowl was not linked to effectiveness of intended messages in those groups. In this study, the shape a respondent preferred was of less importance to policy development than the amount of intended information conveyed by each graphic.", "contents": "An evaluation of dietary guidance graphic alternatives: the evolution of the eating right pyramid. The pyramid graphic was found to be most effective in conveying the messages of moderation and proportionality. The pyramid design might be further strengthened in conveying the total moderation message by including both FOS pictures and symbols in the same graphic. The pyramid also has considerable strength in promoting the message of variety. More important, the pyramid graphic did not convey misinformation about variety, proportionality, and moderation or about the importance of consuming foods in adequate amounts from all the major food groups to achieve a healthful diet. The bowl design was found to be far less effective in promoting the moderation and proportionality messages, but did illustrate the variety message somewhat better than the pyramid. Although respondents indicated a preference for the bowel shape, it is important to note that even in the groups where preference for the bowl was the strongest (i.e., younger, less educated, ethnic minority, and low-income respondents), the pyramid was more likely to be identified as the graphic that suggested the moderation-of-fat message most clearly. Further, preference for the bowl was not linked to effectiveness of intended messages in those groups. In this study, the shape a respondent preferred was of less importance to policy development than the amount of intended information conveyed by each graphic."} {"id": "PMID:1281302", "title": "Embryonic stem (ES) cells lacking functional c-jun: consequences for growth and differentiation, AP-1 activity and tumorigenicity.", "content": "The proto-oncogene c-jun encodes the major component of the transcription factor AP-1 and is thought to have important functions in cell proliferation and differentiation as well as in the cellular response to a variety of external stimuli. To investigate directly the role of c-jun in growth, differentiation and tumorigenicity we generated mouse embryonic stem (ES) cell lines in which both copies of the c-jun gene have been inactivated by homologous recombination. The disruption of both copies of the c-jun gene had no apparent effect on ES cell viability, growth rate and in vitro differentiation potential. Transcriptional activation of the c-jun, junB and c-fos genes following TPA/serum induction was unaffected and efficient transactivation of AP-1 reporter constructs was demonstrated in these cells. Remarkably, subcutaneous injection of ES cells lacking c-Jun into syngeneic mice led to a drastic reduction in the formation of teratocarcinomas. We propose that whereas most of the functions of c-Jun in ES cells appear to be complemented by other Jun proteins in vitro, functional c-Jun protein is essential for efficient tumor growth in vivo.", "contents": "Embryonic stem (ES) cells lacking functional c-jun: consequences for growth and differentiation, AP-1 activity and tumorigenicity. The proto-oncogene c-jun encodes the major component of the transcription factor AP-1 and is thought to have important functions in cell proliferation and differentiation as well as in the cellular response to a variety of external stimuli. To investigate directly the role of c-jun in growth, differentiation and tumorigenicity we generated mouse embryonic stem (ES) cell lines in which both copies of the c-jun gene have been inactivated by homologous recombination. The disruption of both copies of the c-jun gene had no apparent effect on ES cell viability, growth rate and in vitro differentiation potential. Transcriptional activation of the c-jun, junB and c-fos genes following TPA/serum induction was unaffected and efficient transactivation of AP-1 reporter constructs was demonstrated in these cells. Remarkably, subcutaneous injection of ES cells lacking c-Jun into syngeneic mice led to a drastic reduction in the formation of teratocarcinomas. We propose that whereas most of the functions of c-Jun in ES cells appear to be complemented by other Jun proteins in vitro, functional c-Jun protein is essential for efficient tumor growth in vivo."} {"id": "PMID:1281303", "title": "Platelet activation leads to increased c-src kinase activity and association of c-src with an 85-kDa tyrosine phosphoprotein.", "content": "We have used platelets as a model system to study the function of c-src in signal transduction and cell adhesion. Numerous proteins were found to be phosphorylated on tyrosine in response to thrombin-induced platelet activation and aggregation. Two phases of phosphorylation were observed, with the second phase, but not the first, being inhibited by blocking platelet aggregation with an Arg-Gly-Asp-Ser tetrapeptide. As a first step towards identifying those proteins phosphorylated on tyrosine and to determine the specific role of p60src during platelet activation, we looked for changes in p60src kinase activity and for associations of p60src with other tyrosine phosphoproteins. The data presented here demonstrate an increase in p60src kinase activity within 1 min of thrombin-induced activation. Furthermore, p60src transiently associates with a tyrosine phosphoprotein during platelet activation and aggregation. This tyrosine phosphoprotein, p80/85, is a previously characterized cytoskeletal substrate for v-src in transformed cells. The data presented here suggest a model in which p60src functions in platelets to link upstream events, such as cell-surface adhesive interactions, with changes in platelet shape and cytoskeletal organization.", "contents": "Platelet activation leads to increased c-src kinase activity and association of c-src with an 85-kDa tyrosine phosphoprotein. We have used platelets as a model system to study the function of c-src in signal transduction and cell adhesion. Numerous proteins were found to be phosphorylated on tyrosine in response to thrombin-induced platelet activation and aggregation. Two phases of phosphorylation were observed, with the second phase, but not the first, being inhibited by blocking platelet aggregation with an Arg-Gly-Asp-Ser tetrapeptide. As a first step towards identifying those proteins phosphorylated on tyrosine and to determine the specific role of p60src during platelet activation, we looked for changes in p60src kinase activity and for associations of p60src with other tyrosine phosphoproteins. The data presented here demonstrate an increase in p60src kinase activity within 1 min of thrombin-induced activation. Furthermore, p60src transiently associates with a tyrosine phosphoprotein during platelet activation and aggregation. This tyrosine phosphoprotein, p80/85, is a previously characterized cytoskeletal substrate for v-src in transformed cells. The data presented here suggest a model in which p60src functions in platelets to link upstream events, such as cell-surface adhesive interactions, with changes in platelet shape and cytoskeletal organization."} {"id": "PMID:1281304", "title": "Identification and characterization of a cytoskeleton-associated, epidermal growth factor sensitive pp60c-src substrate.", "content": "In studies aimed at identifying and characterizing pp60c-src substrates that participate in the enhanced mitogenic response to epidermal growth factor (EGF) observed in murine C3H10T1/2 fibroblasts overexpressing c-src, we have identified a 75-kDa protein (p75) whose properties are consistent with those expected of such a substrate. We present evidence to show that p75 is immunologically related to a recently described, cytoskeleton-associated, pp60v-src substrate [Wu et al. (1991). Mol. Cell. Biol., 11, 5113-5124), and that its phosphotyrosine content is increased cooperatively by c-src overexpression and EGF stimulation. p75 is rapidly (within 2 min) phosphorylated on tyrosine upon EGF treatment and undergoes a second, prolonged phase of tyrosyl phosphorylation from 7 to 21 h after EGF addition, suggesting that tyrosyl phosphorylation of p75 is important for late as well as early events following EGF receptor activation. Enhanced tyrosyl phosphorylation of p75 is also seen when cells overexpressing c-src are treated with platelet-derived growth factor (PDGF), but significantly less phosphorylation is observed with insulin and fibroblast growth factor (FGF). Both basal and EGF-induced tyrosyl phosphorylation of p75 are reduced in cells overexpressing mutated forms of c-src (unmyristylated, or kinase deficient) as compared with wild-type c-src overexpressers, indicating the dependence of the enhanced tyrosyl phosphorylation on membrane-associated, enzymatically active pp60c-src. In cellular fractionation experiments p75 partitions with the cytosol, while immunofluorescence studies reveal a striking colocalization with pp60c-src at the plasma membrane and in the perinuclear region. Partial co-staining of p75 and actin occurs at the cell's periphery. These data provide evidence for p75 being a direct substrate of pp60c-src. The possible role of p75 in the enhanced response to EGF seen in c-src overexpressers is discussed.", "contents": "Identification and characterization of a cytoskeleton-associated, epidermal growth factor sensitive pp60c-src substrate. In studies aimed at identifying and characterizing pp60c-src substrates that participate in the enhanced mitogenic response to epidermal growth factor (EGF) observed in murine C3H10T1/2 fibroblasts overexpressing c-src, we have identified a 75-kDa protein (p75) whose properties are consistent with those expected of such a substrate. We present evidence to show that p75 is immunologically related to a recently described, cytoskeleton-associated, pp60v-src substrate [Wu et al. (1991). Mol. Cell. Biol., 11, 5113-5124), and that its phosphotyrosine content is increased cooperatively by c-src overexpression and EGF stimulation. p75 is rapidly (within 2 min) phosphorylated on tyrosine upon EGF treatment and undergoes a second, prolonged phase of tyrosyl phosphorylation from 7 to 21 h after EGF addition, suggesting that tyrosyl phosphorylation of p75 is important for late as well as early events following EGF receptor activation. Enhanced tyrosyl phosphorylation of p75 is also seen when cells overexpressing c-src are treated with platelet-derived growth factor (PDGF), but significantly less phosphorylation is observed with insulin and fibroblast growth factor (FGF). Both basal and EGF-induced tyrosyl phosphorylation of p75 are reduced in cells overexpressing mutated forms of c-src (unmyristylated, or kinase deficient) as compared with wild-type c-src overexpressers, indicating the dependence of the enhanced tyrosyl phosphorylation on membrane-associated, enzymatically active pp60c-src. In cellular fractionation experiments p75 partitions with the cytosol, while immunofluorescence studies reveal a striking colocalization with pp60c-src at the plasma membrane and in the perinuclear region. Partial co-staining of p75 and actin occurs at the cell's periphery. These data provide evidence for p75 being a direct substrate of pp60c-src. The possible role of p75 in the enhanced response to EGF seen in c-src overexpressers is discussed."} {"id": "PMID:1281305", "title": "Overexpressed Drosophila src 64B is phosphorylated at its carboxy-terminal tyrosine, but is not catalytically repressed, in cultured Drosophila cells.", "content": "Little is known about the regulation of non-receptor tyrosine kinases in invertebrates. We have studied the relationship between the phosphorylation state of the Drosophila src 64B (Dsrc) gene product, p62D, and its tyrosine kinase activity in Drosophila Schneider 2 cells, using wild-type and mutated Dsrc constructs that were overexpressed by transient transfection. Phosphopeptide mapping showed that the putative regulatory C-terminal tyrosine (Tyr-547) of p62D was phosphorylated in vivo. In contrast to vertebrate src family kinases overexpressed in fibroblasts, wild-type p62D overexpressed in Schneider 2 cells was phosphorylated at additional tyrosines outside of the C-terminus. These tyrosines corresponded to the major in vitro autophosphorylation sites. Overexpression of wild-type p62D or several catalytically active p62D mutants significantly increased the phosphorylation of numerous Schneider cell proteins on tyrosine, while expression of catalytically inactive mutants of p62D had no such effect. Thus, in contrast to the repression of src family kinase activity in fibroblasts, p62D is catalytically active when overexpressed in Drosophila cells, perhaps because of substoichiometric C-terminal tyrosine phosphorylation. These results raise the possibility that fly development will be sensitive to ectopic expression of p62D.", "contents": "Overexpressed Drosophila src 64B is phosphorylated at its carboxy-terminal tyrosine, but is not catalytically repressed, in cultured Drosophila cells. Little is known about the regulation of non-receptor tyrosine kinases in invertebrates. We have studied the relationship between the phosphorylation state of the Drosophila src 64B (Dsrc) gene product, p62D, and its tyrosine kinase activity in Drosophila Schneider 2 cells, using wild-type and mutated Dsrc constructs that were overexpressed by transient transfection. Phosphopeptide mapping showed that the putative regulatory C-terminal tyrosine (Tyr-547) of p62D was phosphorylated in vivo. In contrast to vertebrate src family kinases overexpressed in fibroblasts, wild-type p62D overexpressed in Schneider 2 cells was phosphorylated at additional tyrosines outside of the C-terminus. These tyrosines corresponded to the major in vitro autophosphorylation sites. Overexpression of wild-type p62D or several catalytically active p62D mutants significantly increased the phosphorylation of numerous Schneider cell proteins on tyrosine, while expression of catalytically inactive mutants of p62D had no such effect. Thus, in contrast to the repression of src family kinase activity in fibroblasts, p62D is catalytically active when overexpressed in Drosophila cells, perhaps because of substoichiometric C-terminal tyrosine phosphorylation. These results raise the possibility that fly development will be sensitive to ectopic expression of p62D."} {"id": "PMID:1281306", "title": "Molecular cloning of a family of protein kinase genes expressed in the avian embryo.", "content": "We have used the polymerase chain reaction (PCR) technique to clone kinase-related sequences from avian blastula, neural crest and neural tube mRNA. Twenty-three distinct protein kinase (PK) sequences were amplified, of which eight are identical to previously described PK genes. The cloned molecules fall into three classes: growth factor receptor tyrosine kinases (RTKs), cytosolic tyrosine kinases and serine/threonine kinases. Among the cloned RTKs were the insulin-like growth factor type I receptor, platelet-derived growth factor receptor alpha, the CEK1 fibroblast growth factor (FGF) receptor as well as the avian homolog of a recently cloned PCR fragment related to the eph/elk/eck family, tyro-5. Furthermore, we cloned a novel FGF receptor-like molecule as well as two novel putative RTKs related to the vascular endothelial growth factor (VEGF) receptor. The pattern of expression of the PCR clones was examined by Northern blot analysis of adult tissues: each molecule recognized one or more transcripts of various sizes, suggesting that PK genes may play regulatory roles both in early development and in adult regulation of tissue function. Together with recent studies, this survey confirms the hypothesis that PKs may play important roles in early vertebrate development.", "contents": "Molecular cloning of a family of protein kinase genes expressed in the avian embryo. We have used the polymerase chain reaction (PCR) technique to clone kinase-related sequences from avian blastula, neural crest and neural tube mRNA. Twenty-three distinct protein kinase (PK) sequences were amplified, of which eight are identical to previously described PK genes. The cloned molecules fall into three classes: growth factor receptor tyrosine kinases (RTKs), cytosolic tyrosine kinases and serine/threonine kinases. Among the cloned RTKs were the insulin-like growth factor type I receptor, platelet-derived growth factor receptor alpha, the CEK1 fibroblast growth factor (FGF) receptor as well as the avian homolog of a recently cloned PCR fragment related to the eph/elk/eck family, tyro-5. Furthermore, we cloned a novel FGF receptor-like molecule as well as two novel putative RTKs related to the vascular endothelial growth factor (VEGF) receptor. The pattern of expression of the PCR clones was examined by Northern blot analysis of adult tissues: each molecule recognized one or more transcripts of various sizes, suggesting that PK genes may play regulatory roles both in early development and in adult regulation of tissue function. Together with recent studies, this survey confirms the hypothesis that PKs may play important roles in early vertebrate development."} {"id": "PMID:1281307", "title": "An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain.", "content": "In search of genes possibly involved in the regulation of hindbrain segmentation, we have isolated mouse cDNA clones corresponding to putative protein kinase genes by polymerase chain reaction amplification of cDNA from 9.5-day-old embryo hindbrains. In situ hybridization analysis revealed that one of these genes, Sek, was expressed in an alternating segment-restricted pattern in the developing hindbrain. Isolation and analysis of Sek cDNAs covering the entire coding sequence indicated that Sek encoded a putative receptor protein tyrosine kinase, belonging to the Eph family. These data are consistent with a role of the Sek gene product in a signal transduction process involved in pattern formation in the hindbrain.", "contents": "An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain. In search of genes possibly involved in the regulation of hindbrain segmentation, we have isolated mouse cDNA clones corresponding to putative protein kinase genes by polymerase chain reaction amplification of cDNA from 9.5-day-old embryo hindbrains. In situ hybridization analysis revealed that one of these genes, Sek, was expressed in an alternating segment-restricted pattern in the developing hindbrain. Isolation and analysis of Sek cDNAs covering the entire coding sequence indicated that Sek encoded a putative receptor protein tyrosine kinase, belonging to the Eph family. These data are consistent with a role of the Sek gene product in a signal transduction process involved in pattern formation in the hindbrain."} {"id": "PMID:1281308", "title": "Varicella does not appear to be a cofactor for human immunodeficiency virus infection in children.", "content": "We performed a retrospective analysis of longitudinal clinical and immunologic data obtained from 22 children in the early stages of infection with human immunodeficiency virus (HIV) when they developed varicella. We studied the course of HIV infection to determine whether clinical deterioration occurred after chickenpox. We examined the following indices: growth and development; neurologic status; helper T lymphocyte counts; blood values of core (p24) antigen of HIV; changes in the stage of HIV infection; and need for administration of zidovudine. We studied children for a mean of 2.8 years and for as long as 9.8 years after onset of varicella. There was little evidence that chickenpox affected HIV infection. Three (14%) children developed clinical zoster, 2 of whom (9%) had evidence of chronic infection with varicella-zoster virus. One additional child (5%) had 2 episodes of chickenpox. These observations suggest that children with early HIV infection could be considered for immunization with live attenuated varicella vaccine, which would be predicted to decrease their morbidity from varicella-zoster virus.", "contents": "Varicella does not appear to be a cofactor for human immunodeficiency virus infection in children. We performed a retrospective analysis of longitudinal clinical and immunologic data obtained from 22 children in the early stages of infection with human immunodeficiency virus (HIV) when they developed varicella. We studied the course of HIV infection to determine whether clinical deterioration occurred after chickenpox. We examined the following indices: growth and development; neurologic status; helper T lymphocyte counts; blood values of core (p24) antigen of HIV; changes in the stage of HIV infection; and need for administration of zidovudine. We studied children for a mean of 2.8 years and for as long as 9.8 years after onset of varicella. There was little evidence that chickenpox affected HIV infection. Three (14%) children developed clinical zoster, 2 of whom (9%) had evidence of chronic infection with varicella-zoster virus. One additional child (5%) had 2 episodes of chickenpox. These observations suggest that children with early HIV infection could be considered for immunization with live attenuated varicella vaccine, which would be predicted to decrease their morbidity from varicella-zoster virus."} {"id": "PMID:1281309", "title": "Small-conductance chloride channels induced by cAMP, Ca2+, and hypotonicity in HT29 cells: ion selectivity, additivity and stilbene sensitivity.", "content": "Previous studies in HT29 cells utilizing the cell-attached nystatin (CAN) method [Greger R, Kunzelmann K (1991) Pfl\u00fcgers Arch 419:209-211] have revealed that the Cl- channels induced by cAMP or by increasing cytosolic Ca2+, e.g. by addition of ATP, and by hypotonic cell swelling share in common their conductance, which was so small in our studies [Kunzelmann et al. (1992) Pfl\u00fcgers Arch (in press)] that we could not resolve it at the single-channel level. This prompted the question whether these Cl- conductances can be distinguished in terms of their ion selectivity and sensitivity towards inhibitors. Whether these pathways are additive or not was also examined. The present study utilized the whole-cell patch-clamp and the CAN methods. A total of 160 patches were studied. In whole-cell patches 8-(4-chlorophenylthio)-cAMP (cAMP, 0.1 +/- 1 mmol/l) induced a significant depolarization by 5 mV and a twofold increase in conductance (G) from 6.2 +/- 1.5 nS to 11.7 +/- 3.2 nS (n = 15). Total replacement of Cl- by Br- and I- in cAMP-treated cells hyperpolarized the membrane voltage (V) significantly from -35 +/- 2.8 to -39 +/- 3.4 and -45 +/- 3.3 mV respectively, but had no detectable effect on G, which was 11.9 +/- 3.3 nS in the case of Br- and 11.8 +/- 3.3 nS in the case of I-. Hence, the permselectivity of the cAMP pathway was I- > Br- > Cl-, but the conductances for these anions were all indistinguishable.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Small-conductance chloride channels induced by cAMP, Ca2+, and hypotonicity in HT29 cells: ion selectivity, additivity and stilbene sensitivity. Previous studies in HT29 cells utilizing the cell-attached nystatin (CAN) method [Greger R, Kunzelmann K (1991) Pfl\u00fcgers Arch 419:209-211] have revealed that the Cl- channels induced by cAMP or by increasing cytosolic Ca2+, e.g. by addition of ATP, and by hypotonic cell swelling share in common their conductance, which was so small in our studies [Kunzelmann et al. (1992) Pfl\u00fcgers Arch (in press)] that we could not resolve it at the single-channel level. This prompted the question whether these Cl- conductances can be distinguished in terms of their ion selectivity and sensitivity towards inhibitors. Whether these pathways are additive or not was also examined. The present study utilized the whole-cell patch-clamp and the CAN methods. A total of 160 patches were studied. In whole-cell patches 8-(4-chlorophenylthio)-cAMP (cAMP, 0.1 +/- 1 mmol/l) induced a significant depolarization by 5 mV and a twofold increase in conductance (G) from 6.2 +/- 1.5 nS to 11.7 +/- 3.2 nS (n = 15). Total replacement of Cl- by Br- and I- in cAMP-treated cells hyperpolarized the membrane voltage (V) significantly from -35 +/- 2.8 to -39 +/- 3.4 and -45 +/- 3.3 mV respectively, but had no detectable effect on G, which was 11.9 +/- 3.3 nS in the case of Br- and 11.8 +/- 3.3 nS in the case of I-. Hence, the permselectivity of the cAMP pathway was I- > Br- > Cl-, but the conductances for these anions were all indistinguishable.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281310", "title": "Measurement of cell impedance in frequency domain using discontinuous current clamp and white-noise-modulated current injection.", "content": "A method is described for the determination of cellular input impedance of non-spiking neurones. The input impedance is important when cellular geometry and the effects of voltage-dependent channels are considered. Cells are impaled with a single glass microelectrod and current is injected using a time-sharing technique. The cell's impedance is measured by randomly modulating the injected current and calculating the impedance as a transfer function between current and recorded membrane voltage. Corresponding coherence functions can also be calculated for estimating the signal-to-noise ratio, and also linearity (i.e. possible activation of voltage-dependent conductances) of the membrane.", "contents": "Measurement of cell impedance in frequency domain using discontinuous current clamp and white-noise-modulated current injection. A method is described for the determination of cellular input impedance of non-spiking neurones. The input impedance is important when cellular geometry and the effects of voltage-dependent channels are considered. Cells are impaled with a single glass microelectrod and current is injected using a time-sharing technique. The cell's impedance is measured by randomly modulating the injected current and calculating the impedance as a transfer function between current and recorded membrane voltage. Corresponding coherence functions can also be calculated for estimating the signal-to-noise ratio, and also linearity (i.e. possible activation of voltage-dependent conductances) of the membrane."} {"id": "PMID:1281311", "title": "Nuclear ion channels in cardiac myocytes.", "content": "The paradigm that nucleocytoplasmic transport of ions occurs without a diffusional barrier has been challenged by the recent demonstration with patch-clamp techniques of the existence of ion channels in the nuclear envelope of murine zygotes and hepatocytes. This report demonstrates the existence of nuclear ion channels (NIC) in murine ventricular cardiac myocytes. NIC conductance (gamma), calculated from current histogram peaks, was 106-532 pS at 22-36 degrees C. In nucleus-attached patches, replacement of cytoplasmic K+ with Na+ reduced NIC activity within 30 s, suggesting that intranuclear-delimited mechanisms mediate this phenomenon. In excised, inside-out patches K+ was as permeable as Na+ through NIC. NIC activity was observed in 0-4 mM Mg2+ and/or ATP2-, with or without 0-1 mM Ca2+, indicating a minor direct role of these ions. However, in non-responsive excised inside-out patches, NIC activity appeared when the catalytic subunit of the cAMP-dependent protein kinase was applied to the nucleoplasmic side of the patch, in the presence of Mg2+ and ATP2-, indicating an important role for phosphorylation-dependent process(es) in NIC function--an observation supported by the depressing effects of protein kinase inhibitor on responsive NIC. The concept that nucleopore complexes are solely responsible for nucleocytoplamic transport leads to the speculation that these structures are the physical substrate for NIC.", "contents": "Nuclear ion channels in cardiac myocytes. The paradigm that nucleocytoplasmic transport of ions occurs without a diffusional barrier has been challenged by the recent demonstration with patch-clamp techniques of the existence of ion channels in the nuclear envelope of murine zygotes and hepatocytes. This report demonstrates the existence of nuclear ion channels (NIC) in murine ventricular cardiac myocytes. NIC conductance (gamma), calculated from current histogram peaks, was 106-532 pS at 22-36 degrees C. In nucleus-attached patches, replacement of cytoplasmic K+ with Na+ reduced NIC activity within 30 s, suggesting that intranuclear-delimited mechanisms mediate this phenomenon. In excised, inside-out patches K+ was as permeable as Na+ through NIC. NIC activity was observed in 0-4 mM Mg2+ and/or ATP2-, with or without 0-1 mM Ca2+, indicating a minor direct role of these ions. However, in non-responsive excised inside-out patches, NIC activity appeared when the catalytic subunit of the cAMP-dependent protein kinase was applied to the nucleoplasmic side of the patch, in the presence of Mg2+ and ATP2-, indicating an important role for phosphorylation-dependent process(es) in NIC function--an observation supported by the depressing effects of protein kinase inhibitor on responsive NIC. The concept that nucleopore complexes are solely responsible for nucleocytoplamic transport leads to the speculation that these structures are the physical substrate for NIC."} {"id": "PMID:1281312", "title": "Effects of atrionatriuretic factor on Ca2+ current and Cai-independent transient outward K+ current in human atrial cells.", "content": "The effect of 10 nM atrial natriuretic peptide (ANF) on macroscopic L-type calcium current, ICa, and calcium-independent outward potassium current, Ilo, were studied in myocytes isolated from human atrial trabeculae using the whole-cell-recording patch-clamp technique. When cells were dialysed with pipette media containing 0.2 mM GTP, ANF reduced ICa by 37.81% +/- 5.4% at +20 mV and Ilo by 21.72% +/- 3.68% at +60 mV in a reversible manner. When ICa was increased by beta-adrenoreceptor stimulation (0.1 microM isoproterenol) or by the phosphodiesterase inhibitor isobutylmethylxanthine (10 microM) ANF reduced ICa by 24.99 +/- 3.4% and by 39.9 +/- 6.3% respectively. In cells dialysed with GTP-free pipette media, ANF increased ICa markedly (39.8% +/- 7%) and reversibly, whereas it still depressed Ilo (18.92% +/- 2%). Addition of 0.2 mM GTP[gamma S] to the pipette solution in the absence of GTP increased ICa, decreased Ilo and suppressed the effect of ANF on both ICa and Ilo. It is suggested that activation of the ANF receptor in human atrial cells reduces ICa via guanylate-cyclase-dependent cGMP production, increases ICa via Gs protein activation and decreases Ilo via Gi protein activation.", "contents": "Effects of atrionatriuretic factor on Ca2+ current and Cai-independent transient outward K+ current in human atrial cells. The effect of 10 nM atrial natriuretic peptide (ANF) on macroscopic L-type calcium current, ICa, and calcium-independent outward potassium current, Ilo, were studied in myocytes isolated from human atrial trabeculae using the whole-cell-recording patch-clamp technique. When cells were dialysed with pipette media containing 0.2 mM GTP, ANF reduced ICa by 37.81% +/- 5.4% at +20 mV and Ilo by 21.72% +/- 3.68% at +60 mV in a reversible manner. When ICa was increased by beta-adrenoreceptor stimulation (0.1 microM isoproterenol) or by the phosphodiesterase inhibitor isobutylmethylxanthine (10 microM) ANF reduced ICa by 24.99 +/- 3.4% and by 39.9 +/- 6.3% respectively. In cells dialysed with GTP-free pipette media, ANF increased ICa markedly (39.8% +/- 7%) and reversibly, whereas it still depressed Ilo (18.92% +/- 2%). Addition of 0.2 mM GTP[gamma S] to the pipette solution in the absence of GTP increased ICa, decreased Ilo and suppressed the effect of ANF on both ICa and Ilo. It is suggested that activation of the ANF receptor in human atrial cells reduces ICa via guanylate-cyclase-dependent cGMP production, increases ICa via Gs protein activation and decreases Ilo via Gi protein activation."} {"id": "PMID:1281313", "title": "The effect of hyperosmotic challenge upon ion transport in cultured renal epithelial layers (MDCK).", "content": "Exposure of the basal-lateral surfaces of MDCK epithelia, mounted in Ussing chambers, to medium made hyperosmotic by the non-electrolyte mannitol, resulted in a marked inhibition of the adrenaline-stimulated inward short-circuit current (Cl- secretion). This inhibition was unaccompanied by a reversal of the adrenaline-stimulated increment in tissue conductance, indicating that the inhibition was due to modulation of ion transport at the basal-lateral membranes. Loop-diuretic-sensitive 86Rb(K+) efflux mediated by the Na+ - K+ -2 Cl- cotransporter at the basal-lateral membranes was markedly stimulated by hypertonic exposure. A diuretic-sensitive K+ (Cl-) loss was observed in shrunken cells upon prolonged exposure (20 min), showing that the net direction of \"cotransport\" flux was outward. 86Rb(K+) efflux stimulated by adrenaline (100 microM), exogenous ATP (100 microM) and A23187 (10 microM) was attenuated in shrunken cells, suggesting that basal-lateral K+ conductance is reduced in hyperosmotic media. \"Cotransport\" stimulation by hyperosmotic medium was asymmetric, apical bathing hypertonicity being ineffective. These data are consistent with a low hydraulic permeability of the apical membranes.", "contents": "The effect of hyperosmotic challenge upon ion transport in cultured renal epithelial layers (MDCK). Exposure of the basal-lateral surfaces of MDCK epithelia, mounted in Ussing chambers, to medium made hyperosmotic by the non-electrolyte mannitol, resulted in a marked inhibition of the adrenaline-stimulated inward short-circuit current (Cl- secretion). This inhibition was unaccompanied by a reversal of the adrenaline-stimulated increment in tissue conductance, indicating that the inhibition was due to modulation of ion transport at the basal-lateral membranes. Loop-diuretic-sensitive 86Rb(K+) efflux mediated by the Na+ - K+ -2 Cl- cotransporter at the basal-lateral membranes was markedly stimulated by hypertonic exposure. A diuretic-sensitive K+ (Cl-) loss was observed in shrunken cells upon prolonged exposure (20 min), showing that the net direction of \"cotransport\" flux was outward. 86Rb(K+) efflux stimulated by adrenaline (100 microM), exogenous ATP (100 microM) and A23187 (10 microM) was attenuated in shrunken cells, suggesting that basal-lateral K+ conductance is reduced in hyperosmotic media. \"Cotransport\" stimulation by hyperosmotic medium was asymmetric, apical bathing hypertonicity being ineffective. These data are consistent with a low hydraulic permeability of the apical membranes."} {"id": "PMID:1281314", "title": "Evolutionary conserved nucleotides within the E.coli 4.5S RNA are required for association with P48 in vitro and for optimal function in vivo.", "content": "E.coli 4.5S RNA is homologous to domain IV of eukaryotic SPR7S RNA, the RNA component of the signal recognition particle. The 4.5S RNA is associated in vivo with a 48kD protein (P48), which is homologous to a protein component of the signal recognition particle, SRP54. In addition to secondary structural features, a number of nucleotides are conserved between the 4.5S RNA and domain IV of all other characterised SRP-like RNAs from eubacteria, arachaebacteria and eukaryotes. This domain consists of an extended stem-loop structure; conserved nucleotides lie within the terminal loop and within single-stranded regions bulged from the stem immediately preceding the loop. This conserved region is a candidate for the SRP54/P48 binding site. To determine the functional importance of this region within the 4.5S RNA, mutations were introduced into the 4.5S RNA coding sequence. Mutated alleles were tested for their function in vivo and for the ability of the corresponding RNAs to bind P48 in vitro. Single point mutations in conserved nucleotides within the terminal tetranucleotide loop do not affect P48 binding in vitro and produce only slight growth defects. This suggests that the sequence of the loop may be important for the structure of the molecule rather than for specific interactions with P48. On the other hand, nucleotides within the single-stranded regions bulged from the stem were found to be important both for the binding of P48 to the RNA and for optimal function of the RNA in vivo.", "contents": "Evolutionary conserved nucleotides within the E.coli 4.5S RNA are required for association with P48 in vitro and for optimal function in vivo. E.coli 4.5S RNA is homologous to domain IV of eukaryotic SPR7S RNA, the RNA component of the signal recognition particle. The 4.5S RNA is associated in vivo with a 48kD protein (P48), which is homologous to a protein component of the signal recognition particle, SRP54. In addition to secondary structural features, a number of nucleotides are conserved between the 4.5S RNA and domain IV of all other characterised SRP-like RNAs from eubacteria, arachaebacteria and eukaryotes. This domain consists of an extended stem-loop structure; conserved nucleotides lie within the terminal loop and within single-stranded regions bulged from the stem immediately preceding the loop. This conserved region is a candidate for the SRP54/P48 binding site. To determine the functional importance of this region within the 4.5S RNA, mutations were introduced into the 4.5S RNA coding sequence. Mutated alleles were tested for their function in vivo and for the ability of the corresponding RNAs to bind P48 in vitro. Single point mutations in conserved nucleotides within the terminal tetranucleotide loop do not affect P48 binding in vitro and produce only slight growth defects. This suggests that the sequence of the loop may be important for the structure of the molecule rather than for specific interactions with P48. On the other hand, nucleotides within the single-stranded regions bulged from the stem were found to be important both for the binding of P48 to the RNA and for optimal function of the RNA in vivo."} {"id": "PMID:1281315", "title": "Cleavage efficiencies of model substrates for ribonuclease P from Escherichia coli and Thermus thermophilus.", "content": "We compared cleavage efficiencies of mono-molecular and bipartite model RNAs as substrates for RNase P RNAs (M1 RNAs) and holoenzymes from E. coli and Thermus thermophilus, an extreme thermophilic eubacterium. Acceptor stem and T arm of pre-tRNA substrates are essential recognition elements for both enzymes. Impairing coaxial stacking of acceptor and T stems and omitting the T loop led to reduced cleavage efficiencies. Small model substrates were less efficiently cleaved by M1 RNA and RNase P from T. thermophilus than by the corresponding E. coli activities. Competition kinetics and gel retardation studies showed that truncated tRNA substrates are less tightly bound by RNase P and M1 RNA from both bacteria. Our data further indicate that (pre-)tRNA interacts stronger with E. coli than T. thermophilus M1 RNA. Thus, low cleavage efficiencies of truncated model substrates by T. thermophilus RNase P or M1 RNA could be explained by a critical loss of important contact points between enzyme and substrate. In addition, acceptor stem--T arm substrates, composed of two synthetic RNA fragments, have been designed to mimic internal cleavage of any target RNA molecule available for base pairing.", "contents": "Cleavage efficiencies of model substrates for ribonuclease P from Escherichia coli and Thermus thermophilus. We compared cleavage efficiencies of mono-molecular and bipartite model RNAs as substrates for RNase P RNAs (M1 RNAs) and holoenzymes from E. coli and Thermus thermophilus, an extreme thermophilic eubacterium. Acceptor stem and T arm of pre-tRNA substrates are essential recognition elements for both enzymes. Impairing coaxial stacking of acceptor and T stems and omitting the T loop led to reduced cleavage efficiencies. Small model substrates were less efficiently cleaved by M1 RNA and RNase P from T. thermophilus than by the corresponding E. coli activities. Competition kinetics and gel retardation studies showed that truncated tRNA substrates are less tightly bound by RNase P and M1 RNA from both bacteria. Our data further indicate that (pre-)tRNA interacts stronger with E. coli than T. thermophilus M1 RNA. Thus, low cleavage efficiencies of truncated model substrates by T. thermophilus RNase P or M1 RNA could be explained by a critical loss of important contact points between enzyme and substrate. In addition, acceptor stem--T arm substrates, composed of two synthetic RNA fragments, have been designed to mimic internal cleavage of any target RNA molecule available for base pairing."} {"id": "PMID:1281316", "title": "Amplification of protein expression in a cell free system.", "content": "Large quantities of a catalytically active protein have been produced in a cell free system. More than 10(9) copies of protein were produced from each DNA plasmid containing DNAfol, the bacterial gene encoding dihydrofolate reductase (DHFR). The strategy employed, denoted gene amplification with transcription/translation (GATT), involves sequential coupling of (i) DNA amplification by the polymerase chain reaction (PCR) and (ii) in vitro RNA transcription by T7 RNA polymerase, followed by (iii) translation of the run-off transcripts in a rabbit reticulocyte system. The protein product had the expected size (18 kDa) and catalyzed the NADPH-dependent reduction of 7,8-dihydrofolic acid to 5,6,7,8-tetrahydrofolic acid as efficiently as authentic DHFR. Potential applications of the strategy include large scale production of enzymes containing synthetic amino acids and facilitation of the characterization of the function of genes encountered in genomic mapping studies.", "contents": "Amplification of protein expression in a cell free system. Large quantities of a catalytically active protein have been produced in a cell free system. More than 10(9) copies of protein were produced from each DNA plasmid containing DNAfol, the bacterial gene encoding dihydrofolate reductase (DHFR). The strategy employed, denoted gene amplification with transcription/translation (GATT), involves sequential coupling of (i) DNA amplification by the polymerase chain reaction (PCR) and (ii) in vitro RNA transcription by T7 RNA polymerase, followed by (iii) translation of the run-off transcripts in a rabbit reticulocyte system. The protein product had the expected size (18 kDa) and catalyzed the NADPH-dependent reduction of 7,8-dihydrofolic acid to 5,6,7,8-tetrahydrofolic acid as efficiently as authentic DHFR. Potential applications of the strategy include large scale production of enzymes containing synthetic amino acids and facilitation of the characterization of the function of genes encountered in genomic mapping studies."} {"id": "PMID:1281317", "title": "In vitro effect of antisense oligonucleotides on human immunodeficiency virus type 1 reverse transcription.", "content": "The molecular events involved in antisense-mediated inhibition of retroviral transcription were studied by analyzing the in vitro effect of antisense oligodeoxynucleotides on reverse transcription by Human Immunodeficiency Virus type 1 (HIV-1) reverse transcriptase (RT). Oligonucleotides have been designed to be complementary to three targets located in the 5' region of the HIV-1 RNA genome: the transactivating response element (TAR), the U5 region and a sequence contiguous to the primer binding site (PrePBS). Antisense oligodeoxynucleotides were used with their 3'-OH end either free or blocked by a dideoxynucleotide in order to avoid cDNA synthesis. Experiments with two recombinant forms of HIV RT, carrying or not RNase H activity, showed that antisense oligonucleotides can arrest reverse transcription by an RNase H-independent mechanism. The AntiTAR oligonucleotide did not affect reverse transcription. In contrast, the AntiU5 and AntiPrePBS oligonucleotides led to an efficient inhibition of both forms of HIV RT. In the case of the AntiU5, the inhibition obtained in the absence of the RNase H activity indicates that this effect can be related to features of the RNA secondary structure. The AntiPrePBS oligonucleotide did bind to its target only in the presence of PBS primer. Use of shifted oligonucleotides showed that the AntiPrePBS inhibitory effect depends on a cooperative annealing with the AntiPBS primer on the template.", "contents": "In vitro effect of antisense oligonucleotides on human immunodeficiency virus type 1 reverse transcription. The molecular events involved in antisense-mediated inhibition of retroviral transcription were studied by analyzing the in vitro effect of antisense oligodeoxynucleotides on reverse transcription by Human Immunodeficiency Virus type 1 (HIV-1) reverse transcriptase (RT). Oligonucleotides have been designed to be complementary to three targets located in the 5' region of the HIV-1 RNA genome: the transactivating response element (TAR), the U5 region and a sequence contiguous to the primer binding site (PrePBS). Antisense oligodeoxynucleotides were used with their 3'-OH end either free or blocked by a dideoxynucleotide in order to avoid cDNA synthesis. Experiments with two recombinant forms of HIV RT, carrying or not RNase H activity, showed that antisense oligonucleotides can arrest reverse transcription by an RNase H-independent mechanism. The AntiTAR oligonucleotide did not affect reverse transcription. In contrast, the AntiU5 and AntiPrePBS oligonucleotides led to an efficient inhibition of both forms of HIV RT. In the case of the AntiU5, the inhibition obtained in the absence of the RNase H activity indicates that this effect can be related to features of the RNA secondary structure. The AntiPrePBS oligonucleotide did bind to its target only in the presence of PBS primer. Use of shifted oligonucleotides showed that the AntiPrePBS inhibitory effect depends on a cooperative annealing with the AntiPBS primer on the template."} {"id": "PMID:1281319", "title": "Inhibition of 3 alpha-hydroxysteroid oxidoreductase and 5 alpha-reductase activity by antiandrogens and indomethacin in the rat prostate.", "content": "We studied the effects of antiandrogens in vitro on inhibition of 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) and 5 alpha-reductase activities in the rat prostate. Kinetic and inhibition experiments were analyzed by thin layer chromatography. Cyproterone acetate (CA), chlormadinone acetate (CMA), and TZP-4238 (TZP), which is more potent than other antiandrogens, were used as inhibitors and were compared with indomethacin IND, which is a recognized 3 alpha-HSOR inhibitor. The IC50S of CA, CMA, IND, and TZP for 3 alpha-HSOR reductase in cytosol were about 5, 10, 10, and 100 microM, respectively, and inhibition was competitive. The IC50 of IND for 3 alpha-HSOR reductase in microsomes was 20 microM. The IC50S of other inhibitors were > 100 microM, and inhibition was noncompetitive. The IC50S of CA, CMA, IND, and TZP for 3 alpha-HSOR oxidase in cytosol were > 100 microM, and inhibition was competitive or noncompetitive. Inhibition of 3 alpha-HSOR oxidation was not observed in microsomes. The difference between these inhibition patterns suggests that there may be 4 isoenzymes in rat prostatic tissue. The IC50S of MK-906, CMA, and TZP for 5 alpha-reductase in prostate homogenate were about 0.01, 200, and 200 microM, respectively.", "contents": "Inhibition of 3 alpha-hydroxysteroid oxidoreductase and 5 alpha-reductase activity by antiandrogens and indomethacin in the rat prostate. We studied the effects of antiandrogens in vitro on inhibition of 3 alpha-hydroxysteroid oxidoreductase (3 alpha-HSOR) and 5 alpha-reductase activities in the rat prostate. Kinetic and inhibition experiments were analyzed by thin layer chromatography. Cyproterone acetate (CA), chlormadinone acetate (CMA), and TZP-4238 (TZP), which is more potent than other antiandrogens, were used as inhibitors and were compared with indomethacin IND, which is a recognized 3 alpha-HSOR inhibitor. The IC50S of CA, CMA, IND, and TZP for 3 alpha-HSOR reductase in cytosol were about 5, 10, 10, and 100 microM, respectively, and inhibition was competitive. The IC50 of IND for 3 alpha-HSOR reductase in microsomes was 20 microM. The IC50S of other inhibitors were > 100 microM, and inhibition was noncompetitive. The IC50S of CA, CMA, IND, and TZP for 3 alpha-HSOR oxidase in cytosol were > 100 microM, and inhibition was competitive or noncompetitive. Inhibition of 3 alpha-HSOR oxidation was not observed in microsomes. The difference between these inhibition patterns suggests that there may be 4 isoenzymes in rat prostatic tissue. The IC50S of MK-906, CMA, and TZP for 5 alpha-reductase in prostate homogenate were about 0.01, 200, and 200 microM, respectively."} {"id": "PMID:1281320", "title": "Measurement of androgen sensitivity in the human prostate in in vitro three-dimensional histoculture.", "content": "We have adopted an in vitro three-dimensional histoculture technique for assay of androgen sensitivity in explants of human benign prostatic tissue. The assay is based on the uptake of 3H-thymidine/micrograms protein in explants of prostate incubated in parallel with dihydrotestosterone (DHT) and hydroxyflutamide (HF) controls. The ratio of 3H-thymidine/micrograms protein in DHT treated samples per 3H-thymidine/micrograms protein in HF treated samples provides an index of androgen sensitivity. The DHT/HF index measured in 24 BPH specimens averaged 3.6. To determine the specificity of the HF effect, we measured the DHT/HF index in a single prostate at different concentrations of HF in the presence of fixed concentrations of DHT (2 x 10(-8) M) and noted a dose-response relationship. In addition we noted no effects of HF on 3H-thymidine incorporation over a range of 2 x 10(-4)M compared to 2 x 10(-7)M, except at the highest concentration. Of surprise was the finding of an average DHT/HF index in 5 different nonprostate tissues, including breast, uterus, colon, kidney, and thyroid, that was similar to the index found in prostates. We plan to adapt this androgen sensitivity assay to measure the DHT/HF index in biopsy-size samples of prostate, since such an assay could then be utilized to determine androgen sensitivity in individual patients with prostate cancer.", "contents": "Measurement of androgen sensitivity in the human prostate in in vitro three-dimensional histoculture. We have adopted an in vitro three-dimensional histoculture technique for assay of androgen sensitivity in explants of human benign prostatic tissue. The assay is based on the uptake of 3H-thymidine/micrograms protein in explants of prostate incubated in parallel with dihydrotestosterone (DHT) and hydroxyflutamide (HF) controls. The ratio of 3H-thymidine/micrograms protein in DHT treated samples per 3H-thymidine/micrograms protein in HF treated samples provides an index of androgen sensitivity. The DHT/HF index measured in 24 BPH specimens averaged 3.6. To determine the specificity of the HF effect, we measured the DHT/HF index in a single prostate at different concentrations of HF in the presence of fixed concentrations of DHT (2 x 10(-8) M) and noted a dose-response relationship. In addition we noted no effects of HF on 3H-thymidine incorporation over a range of 2 x 10(-4)M compared to 2 x 10(-7)M, except at the highest concentration. Of surprise was the finding of an average DHT/HF index in 5 different nonprostate tissues, including breast, uterus, colon, kidney, and thyroid, that was similar to the index found in prostates. We plan to adapt this androgen sensitivity assay to measure the DHT/HF index in biopsy-size samples of prostate, since such an assay could then be utilized to determine androgen sensitivity in individual patients with prostate cancer."} {"id": "PMID:1281321", "title": "Lymphatic drainage of the prostate gland in canines.", "content": "Lymphography of the penis was performed in 3 canines, and direct intraprostatic injection of India ink was carried out in 8 canines to visualize lymphatic drainage of the prostate gland. In penile lymphography, the contrast medium drained in 2 directions: (1) lymphatic drainage into the external and common iliac lymph nodes through the superficial inguinal lymph nodes; (2) lymphatic drainage into the presacral lymph nodes along the urethra and posterior wall of the pelvis. Lymphatics of the prostate gland drained in 3 directions: (1) lymphatics from the prostate gland mainly drained along the prostatic and internal iliac vessels into the internal and common iliac lymph nodes, (2) lymphatics from the dorsal region near the urinary bladder drained along the ureter into the common iliac lymph nodes, and (3) lymphatics from the apex of the prostate gland drained along the posterior wall of the pelvis into the presacral lymph nodes. Prostate cancer developed at the apex is estimated to preferentially metastasize to the presacral lymph nodes, and drug injection into the penile lymphatics is considered to be a good route to treat metastases of lymph nodes in the pelvis.", "contents": "Lymphatic drainage of the prostate gland in canines. Lymphography of the penis was performed in 3 canines, and direct intraprostatic injection of India ink was carried out in 8 canines to visualize lymphatic drainage of the prostate gland. In penile lymphography, the contrast medium drained in 2 directions: (1) lymphatic drainage into the external and common iliac lymph nodes through the superficial inguinal lymph nodes; (2) lymphatic drainage into the presacral lymph nodes along the urethra and posterior wall of the pelvis. Lymphatics of the prostate gland drained in 3 directions: (1) lymphatics from the prostate gland mainly drained along the prostatic and internal iliac vessels into the internal and common iliac lymph nodes, (2) lymphatics from the dorsal region near the urinary bladder drained along the ureter into the common iliac lymph nodes, and (3) lymphatics from the apex of the prostate gland drained along the posterior wall of the pelvis into the presacral lymph nodes. Prostate cancer developed at the apex is estimated to preferentially metastasize to the presacral lymph nodes, and drug injection into the penile lymphatics is considered to be a good route to treat metastases of lymph nodes in the pelvis."} {"id": "PMID:1281322", "title": "The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle.", "content": "The objective of the present study was to determine whether the smooth muscle content of the prostate adenoma is related to the clinical response to terazosin, a long-acting selective alpha 1 blocker. Multiple random biopsies of the prostate were obtained from 26 male subjects with symptomatic benign prostatic hyperplasia (BPH) prior to initiating therapy with terazosin. Double immunoenzymatic staining and computer-assisted quantitative color image analysis were utilized to quantify the area density of smooth muscle, connective tissue, glandular epithelium, and glandular lumen. The clinical response to alpha blockade was based upon changes in peak urinary flow rate and the Boyarsky symptom score. A significant direct relationship was observed between the percent area density of smooth muscle and the percent change in peak urinary flow rate. A statistically significant correlation between the percent area density of smooth muscle and the percent change in Boyarsky symptom score was not observed. The percent area density of prostate smooth muscle in the subjects exhibiting a favorable clinical response was 38% greater than the nonresponders (P = 0.068). The clinical response to alpha blockade in BPH is related to the area density of prostate smooth muscle.", "contents": "The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle. The objective of the present study was to determine whether the smooth muscle content of the prostate adenoma is related to the clinical response to terazosin, a long-acting selective alpha 1 blocker. Multiple random biopsies of the prostate were obtained from 26 male subjects with symptomatic benign prostatic hyperplasia (BPH) prior to initiating therapy with terazosin. Double immunoenzymatic staining and computer-assisted quantitative color image analysis were utilized to quantify the area density of smooth muscle, connective tissue, glandular epithelium, and glandular lumen. The clinical response to alpha blockade was based upon changes in peak urinary flow rate and the Boyarsky symptom score. A significant direct relationship was observed between the percent area density of smooth muscle and the percent change in peak urinary flow rate. A statistically significant correlation between the percent area density of smooth muscle and the percent change in Boyarsky symptom score was not observed. The percent area density of prostate smooth muscle in the subjects exhibiting a favorable clinical response was 38% greater than the nonresponders (P = 0.068). The clinical response to alpha blockade in BPH is related to the area density of prostate smooth muscle."} {"id": "PMID:1281323", "title": "Immunohistochemical evidence of the existence and localization of aromatase in human prostatic tissues.", "content": "Estrogens may be involved in normal growth of the prostate and the development of benign prostatic hyperplasia (BPH). The location of estrogen production is still unclear, and there has never been a direct evidence for the existence of the aromatase system, which converts androgens to estrogens, in the prostate. Using an avidin-biotin technique with a polyclonal anti-human placental aromatase, we demonstrated the existence of aromatase in normal prostates of young men and BPH tissue from elderly men. The staining is more pronounced in the stroma. However, positive stains were also seen in the glandular epithelium. While evidence of the existence of an enzyme system does not equal demonstration of its activity in a specific tissue site, our findings suggest that local estrogen production in the stroma and/or epithelium of the prostate may play a role in the maintenance of normal growth and development of BPH.", "contents": "Immunohistochemical evidence of the existence and localization of aromatase in human prostatic tissues. Estrogens may be involved in normal growth of the prostate and the development of benign prostatic hyperplasia (BPH). The location of estrogen production is still unclear, and there has never been a direct evidence for the existence of the aromatase system, which converts androgens to estrogens, in the prostate. Using an avidin-biotin technique with a polyclonal anti-human placental aromatase, we demonstrated the existence of aromatase in normal prostates of young men and BPH tissue from elderly men. The staining is more pronounced in the stroma. However, positive stains were also seen in the glandular epithelium. While evidence of the existence of an enzyme system does not equal demonstration of its activity in a specific tissue site, our findings suggest that local estrogen production in the stroma and/or epithelium of the prostate may play a role in the maintenance of normal growth and development of BPH."} {"id": "PMID:1281324", "title": "Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia.", "content": "The effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One- to 2-year-old beagle dogs were castrated and administered 75 mg/week of androstanediol (A-diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP-4238, 0.1 mg/kg/day of TZP-4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A-diol plus E2. Treatment with 0.5 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP-4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/kg/day of TZP-4238 decreased 5 alpha-reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP-4238 and CMA were effective in inhibiting the growth of hormone-induced canine BPH, and TZP-4238 was at least 5 times more potent than CMA. TZP-4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen-AR complex. TZP-4238 decreased 5 alpha-reductase activity by prevention of the androgen action described above.", "contents": "Effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia. The effects of the new steroidal antiandrogen TZP-4238 on hormone-induced canine prostatic hyperplasia (BPH) were studied in comparison with those of chlormadinone acetate (CMA), a steroidal antiandrogen used in Japan. One- to 2-year-old beagle dogs were castrated and administered 75 mg/week of androstanediol (A-diol) plus 0.75 mg/week of estradiol (E2) for 25 weeks. These dogs were treated orally with placebo, 0.5 mg/kg/day of TZP-4238, 0.1 mg/kg/day of TZP-4238, and 2.5 mg/kg/day of CMA, respectively, for 21 weeks after 4 weeks treatment with A-diol plus E2. Treatment with 0.5 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA suppressed prostatic growth, and treatment with 0.1 mg/kg/day of TZP-4238 suppressed prostatic growth slightly. Treatment with 0.5 mg/kg/day of TZP-4238 decreased 5 alpha-reductase activity, DHT content, and nuclear androgen receptor (AR) content in the prostate, and treatment with 0.1 mg/kg/day of TZP-4238 or 2.5 mg/kg/day of CMA also decreased or tended to decrease these parameters. In conclusion, TZP-4238 and CMA were effective in inhibiting the growth of hormone-induced canine BPH, and TZP-4238 was at least 5 times more potent than CMA. TZP-4238 inhibited prostatic growth by decreasing prostatic androgen content and the androgen-AR complex. TZP-4238 decreased 5 alpha-reductase activity by prevention of the androgen action described above."} {"id": "PMID:1281328", "title": "Pore size and negative charge as structural determinants of permeability in the Torpedo nicotinic acetylcholine receptor channel.", "content": "To gain an insight into the molecular basis of ion permeation mechanism through the nicotinic acetylcholine receptor (AChR) channel, we have determined permeability ratios of organic cations relative to Na+ of specifically mutated Torpedo californica AChR channels expressed in Xenopus oocytes. The mutations involved mainly the side chains of the amino acid residues in the intermediate ring, where mutations have been found to exert strong effects on single-channel conductance and ion selectivity among alkali metal cations. The results obtained reveal that both the size and the net charge of the side chains of the intermediate ring are involved in determining the permeability, and provide experimental evidence that the pore size at the intermediate ring is a critical determinant of permeability. Our findings further suggest that changes in net charge exert effects on permeability by affecting the pore size of the channel.", "contents": "Pore size and negative charge as structural determinants of permeability in the Torpedo nicotinic acetylcholine receptor channel. To gain an insight into the molecular basis of ion permeation mechanism through the nicotinic acetylcholine receptor (AChR) channel, we have determined permeability ratios of organic cations relative to Na+ of specifically mutated Torpedo californica AChR channels expressed in Xenopus oocytes. The mutations involved mainly the side chains of the amino acid residues in the intermediate ring, where mutations have been found to exert strong effects on single-channel conductance and ion selectivity among alkali metal cations. The results obtained reveal that both the size and the net charge of the side chains of the intermediate ring are involved in determining the permeability, and provide experimental evidence that the pore size at the intermediate ring is a critical determinant of permeability. Our findings further suggest that changes in net charge exert effects on permeability by affecting the pore size of the channel."} {"id": "PMID:1281329", "title": "Involvement of prostanoids in the regulation of angiogenesis by polypeptide growth factors.", "content": "Polypeptide growth factors (PGFs), mainly those of the fibroblast growth factor (FGF) family, have been shown to be capable of regulating angiogenesis. Although many data have been accumulated during this last year on the mechanism of action of PGF, little is known about a possible identification of second messengers signalling to the cell the occupancy of the receptor by its ligand. We have previously proposed that arachidonic acid or its derivatives may play a role as PGF second messengers. In the present paper we described a modification of the chorioallanthoic membrane (CAM) technique, involving the use of labelled sulphate to follow the angiogenic process. Thus we have been able to correlate morphological observation of CAMs development with incorporation of labelled sulphate in a stable form. Here we show that, as expected, PGF as endothelial cell growth factor (ECGS) or basic fibroblast growth factor (bFGF) potentiate the incorporation of radioactivity into CAMs at concentrations which for bFGF are of the order of 1.5 micrograms/egg. This effect can be correlated to the generation of prostanoids by two kinds of approach: A) PGE1 injected into eggs was capable of strongly increasing labelling of CAMs; B) Indomethacin had a dramatic effect on embryo survival as well as on CAM development, decreasing both at very low concentration (50 survival rate observable at 2 micrograms/egg). Finally vanadate, which is known to inhibit tyrosine phosphatase, was capable of potentiating the effect of PGF on angiogenesis. Thus it appears that products of the prostaglandin H synthase pathway behave as mediators of PGF control of angiogenesis.", "contents": "Involvement of prostanoids in the regulation of angiogenesis by polypeptide growth factors. Polypeptide growth factors (PGFs), mainly those of the fibroblast growth factor (FGF) family, have been shown to be capable of regulating angiogenesis. Although many data have been accumulated during this last year on the mechanism of action of PGF, little is known about a possible identification of second messengers signalling to the cell the occupancy of the receptor by its ligand. We have previously proposed that arachidonic acid or its derivatives may play a role as PGF second messengers. In the present paper we described a modification of the chorioallanthoic membrane (CAM) technique, involving the use of labelled sulphate to follow the angiogenic process. Thus we have been able to correlate morphological observation of CAMs development with incorporation of labelled sulphate in a stable form. Here we show that, as expected, PGF as endothelial cell growth factor (ECGS) or basic fibroblast growth factor (bFGF) potentiate the incorporation of radioactivity into CAMs at concentrations which for bFGF are of the order of 1.5 micrograms/egg. This effect can be correlated to the generation of prostanoids by two kinds of approach: A) PGE1 injected into eggs was capable of strongly increasing labelling of CAMs; B) Indomethacin had a dramatic effect on embryo survival as well as on CAM development, decreasing both at very low concentration (50 survival rate observable at 2 micrograms/egg). Finally vanadate, which is known to inhibit tyrosine phosphatase, was capable of potentiating the effect of PGF on angiogenesis. Thus it appears that products of the prostaglandin H synthase pathway behave as mediators of PGF control of angiogenesis."} {"id": "PMID:1281330", "title": "Convergent and overlapping transcripts of the Chlamydia trachomatis 7.5-kb plasmid.", "content": "Transcription of the 7.5-kb cryptic plasmid of Chlamydia trachomatis serovar L2 was investigated. Faint, diffuse transcripts of about 1.6 and 2.2 kb and intense short transcripts of about 250 and 430 bases were identified by Northern blot analysis. The short transcripts were found to have a common 5' end corresponding to bp 501 relative to the unique BamHI site of the plasmid and to terminate at different downstream sites. Putative promoter sequences of TTGCCA and TATATT, which closely resemble the consensus recognition site of Escherichia coli sigma 70, were identified at the -35 and -10 positions upstream from the 5' end of the short transcripts made in chlamydia. Transcripts of similar sizes were also expressed from this promoter in E. coli harboring a recombinant plasmid encoding the short transcripts. The short transcripts encode a common open reading frame (ORF) of 34 codons; however, a strong ribosome binding site was not found in the vicinity of the initiator codon, and it is not known whether the transcripts are translated in vivo. A large ORF of 330 codons, which has been shown to encode a hypothetical protein containing conserved domains of recombinase-like proteins, is antisense to the short transcripts. Transcripts encoding the large ORF could not be detected directly by Northern blot or primer extension analysis. However, transcripts were detected by polymerase chain reaction amplification of the large ORF cDNA and when Southern blots of single-stranded antisense DNA for the large ORF were probed with radiolabeled RNA synthesized by host-free chlamydial reticulate bodies. Thus, both strands of the chlamydial plasmid are transcribed in the region encoding the short transcripts. We propose that the short transcripts play a regulatory role as antisense RNAs.", "contents": "Convergent and overlapping transcripts of the Chlamydia trachomatis 7.5-kb plasmid. Transcription of the 7.5-kb cryptic plasmid of Chlamydia trachomatis serovar L2 was investigated. Faint, diffuse transcripts of about 1.6 and 2.2 kb and intense short transcripts of about 250 and 430 bases were identified by Northern blot analysis. The short transcripts were found to have a common 5' end corresponding to bp 501 relative to the unique BamHI site of the plasmid and to terminate at different downstream sites. Putative promoter sequences of TTGCCA and TATATT, which closely resemble the consensus recognition site of Escherichia coli sigma 70, were identified at the -35 and -10 positions upstream from the 5' end of the short transcripts made in chlamydia. Transcripts of similar sizes were also expressed from this promoter in E. coli harboring a recombinant plasmid encoding the short transcripts. The short transcripts encode a common open reading frame (ORF) of 34 codons; however, a strong ribosome binding site was not found in the vicinity of the initiator codon, and it is not known whether the transcripts are translated in vivo. A large ORF of 330 codons, which has been shown to encode a hypothetical protein containing conserved domains of recombinase-like proteins, is antisense to the short transcripts. Transcripts encoding the large ORF could not be detected directly by Northern blot or primer extension analysis. However, transcripts were detected by polymerase chain reaction amplification of the large ORF cDNA and when Southern blots of single-stranded antisense DNA for the large ORF were probed with radiolabeled RNA synthesized by host-free chlamydial reticulate bodies. Thus, both strands of the chlamydial plasmid are transcribed in the region encoding the short transcripts. We propose that the short transcripts play a regulatory role as antisense RNAs."} {"id": "PMID:1281331", "title": "[The epidemiology of adverse reactions to nonsteroidal anti-inflammatory drugs. Nimesulide is tolerated by patients with adverse reactions to NSAIDs and modulates in man the skin response to histamine and codeine].", "content": "We evaluated the tolerance to NIM in patients with adverse reactions to NSAIDs, expressed by urticaria-angioedema, bronchial asthma or erythema polymorphous on 92 patients among which 32 atopics affected by asthma, rhinitis or contact dermatitis. Challenge test has been performed with increasing amounts of NIM per os every 2 hrs to a maximum of 100 mg/dose. The last dosage was repeated every 12 hrs for 4 times more. No reactions were observed in 86 patients (93.4%). Moreover we evaluated the efficacy of NIM in modulating pomphoid cutaneous reaction to histamine (HIS) and codeine (COD). Three subjects were prick tested with HIS and COD solutions at different concentrations (0.1 to 10 mg/ml), before and after a 5 days therapy with NIM at different dosages/kg/die. At NIM dosages of 3.7 and 2.7 mg/kg/die we observed a strong reduction of pomphoid activity of both HIS and COD. No clear effects were detected at 2.2 mg/kg/die dosage. We assume a dose-related in vivo inhibitory effect of NIM on cutaneous mast cells releasability or a direct anti-histaminic effect. We point out the possible therapeutic role of NIM in the treatment of allergic flogosis at steroid and cromon's side.", "contents": "[The epidemiology of adverse reactions to nonsteroidal anti-inflammatory drugs. Nimesulide is tolerated by patients with adverse reactions to NSAIDs and modulates in man the skin response to histamine and codeine]. We evaluated the tolerance to NIM in patients with adverse reactions to NSAIDs, expressed by urticaria-angioedema, bronchial asthma or erythema polymorphous on 92 patients among which 32 atopics affected by asthma, rhinitis or contact dermatitis. Challenge test has been performed with increasing amounts of NIM per os every 2 hrs to a maximum of 100 mg/dose. The last dosage was repeated every 12 hrs for 4 times more. No reactions were observed in 86 patients (93.4%). Moreover we evaluated the efficacy of NIM in modulating pomphoid cutaneous reaction to histamine (HIS) and codeine (COD). Three subjects were prick tested with HIS and COD solutions at different concentrations (0.1 to 10 mg/ml), before and after a 5 days therapy with NIM at different dosages/kg/die. At NIM dosages of 3.7 and 2.7 mg/kg/die we observed a strong reduction of pomphoid activity of both HIS and COD. No clear effects were detected at 2.2 mg/kg/die dosage. We assume a dose-related in vivo inhibitory effect of NIM on cutaneous mast cells releasability or a direct anti-histaminic effect. We point out the possible therapeutic role of NIM in the treatment of allergic flogosis at steroid and cromon's side."} {"id": "PMID:1281332", "title": "Metabolism of FK 506 in differentially induced rat liver microsomes.", "content": "The in vitro hepatic metabolism of FK 506 was studied in microsomes prepared from control rats as well as in microsomes prepared from rats treated with the selective cytochrome P-450 isozyme inducers 3-methylcholanthrene (IA), phenobarbital (IIB), and dexamethasone (IIIA). The metabolism of FK 506 was similar for control microsomes and for microsomes prepared from phenobarbital and 3-methylcholanthrene induced animals. The percentage of FK 506 metabolized by these tissue preparations ranged from 21.7 to 32.7%. In contrast, the percentage of FK 506 metabolized by dexamethasone induced microsomes was 86.4%. The metabolism of FK 506 was not effected when the selective IA and IIB isozyme inhibitors alpha-naphthoflavone and orphenadrine were added to the incubations. However, the metabolism of FK 506 decreased by approximately 44% when the IIIA specific isozyme inhibitor troleandomycin was added to the dexamethasone induced microsomes. Therefore, the metabolism of FK 506 is apparently mediated primarily by the steroid inducible cytochrome P-450 IIIA isozyme.", "contents": "Metabolism of FK 506 in differentially induced rat liver microsomes. The in vitro hepatic metabolism of FK 506 was studied in microsomes prepared from control rats as well as in microsomes prepared from rats treated with the selective cytochrome P-450 isozyme inducers 3-methylcholanthrene (IA), phenobarbital (IIB), and dexamethasone (IIIA). The metabolism of FK 506 was similar for control microsomes and for microsomes prepared from phenobarbital and 3-methylcholanthrene induced animals. The percentage of FK 506 metabolized by these tissue preparations ranged from 21.7 to 32.7%. In contrast, the percentage of FK 506 metabolized by dexamethasone induced microsomes was 86.4%. The metabolism of FK 506 was not effected when the selective IA and IIB isozyme inhibitors alpha-naphthoflavone and orphenadrine were added to the incubations. However, the metabolism of FK 506 decreased by approximately 44% when the IIIA specific isozyme inhibitor troleandomycin was added to the dexamethasone induced microsomes. Therefore, the metabolism of FK 506 is apparently mediated primarily by the steroid inducible cytochrome P-450 IIIA isozyme."} {"id": "PMID:1281333", "title": "The effect of ruthenium red during Ca2+ depletion and repletion in the isolated perfused rat liver.", "content": "Perfusion of rat liver with Ca(2+)-depleted buffer induces oxidative stress and liver damage, which can be prevented by Ca2+ repletion (Okuda et al. J Lab Clin Med). In the present study, we investigated the action of ruthenium red on acute Ca2+ loading after Ca2+ depletion in the isolated perfused rat liver. The major findings of this study are that 1) Ca2+ depletion-induced liver damage was related to mitochondrial disfunction; 2) ruthenium red inhibited the oxidative stress and liver damage normally seen during Ca2+ depletion; 3) ruthenium red inhibited the Ca2+ depletion-induced mitochondrial disfunction. These observations suggest that mitochondrial Ca2+ cycling is responsible for Ca2+ depletion-induced oxidative stress and liver damage.", "contents": "The effect of ruthenium red during Ca2+ depletion and repletion in the isolated perfused rat liver. Perfusion of rat liver with Ca(2+)-depleted buffer induces oxidative stress and liver damage, which can be prevented by Ca2+ repletion (Okuda et al. J Lab Clin Med). In the present study, we investigated the action of ruthenium red on acute Ca2+ loading after Ca2+ depletion in the isolated perfused rat liver. The major findings of this study are that 1) Ca2+ depletion-induced liver damage was related to mitochondrial disfunction; 2) ruthenium red inhibited the oxidative stress and liver damage normally seen during Ca2+ depletion; 3) ruthenium red inhibited the Ca2+ depletion-induced mitochondrial disfunction. These observations suggest that mitochondrial Ca2+ cycling is responsible for Ca2+ depletion-induced oxidative stress and liver damage."} {"id": "PMID:1281335", "title": "Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients.", "content": "Circulating monoclonal B cells in peripheral blood from patients with multiple myeloma or with monoclonal gammopathy of undetermined significance (MGUS) have previously been shown to express CD19, CD20, and PCA-1 and are predominantly CD45R0+, characterizing them as very late stage B cells. This work shows that the abnormal B cells are monoclonal as defined by their exclusive expression of either kappa or lambda light chain mRNA, and that the same type of light chain mRNA is expressed in both bone marrow plasma cells and blood B cells. These abnormal tumour-related circulating B cells express high densities of CD11b, a beta 2-integrin, which is expressed in a conformationally active state as defined by reactivity with monoclonal antibody 7E3. Normal peripheral blood B cells which do not bear CD11b acquire a high density after stimulation with pokeweed mitogen (PWM). At day 4 of culture, the expression of CD11b on normal CD19+ B cells was nearly comparable to that of the circulating myeloma late stage B cells. After PWM stimulation of circulating myeloma B cells the expression of CD11b was gradually lost during 4 days of culture, suggesting that its expression is dynamically regulated. Two patients with no phenotypically abnormal B cells in their blood at diagnosis acquired a large subset of CD11b+ B cells 4 weeks after initiation of chemotherapy. In most patients, a subset of the circulating myeloma B cells express a low density of CD5. The proportion of CD19+ B cells in the bone marrow expressing CD11b was much reduced compared with peripheral blood B cells, and CD11b was not detectable on plasma cells in the bone marrow, suggesting a sequential relationship of the B-cell subsets detected in our population of patients, involving gradual loss of CD11b concurrent with the loss of CD19 during B lineage differentiation. These cells appear to represent a continuously differentiating monoclonal B lineage culminating in the CD11b- plasma cell entrenched in the bone marrow. We speculate that the expression of conformationally active CD11b on the abnormal B cells in peripheral blood mononuclear cells of myeloma patients facilitates transendothelial migration of circulating myeloma B cells to the bone marrow.", "contents": "Restricted expression of immunoglobulin light chain mRNA and of the adhesion molecule CD11b on circulating monoclonal B lineage cells in peripheral blood of myeloma patients. Circulating monoclonal B cells in peripheral blood from patients with multiple myeloma or with monoclonal gammopathy of undetermined significance (MGUS) have previously been shown to express CD19, CD20, and PCA-1 and are predominantly CD45R0+, characterizing them as very late stage B cells. This work shows that the abnormal B cells are monoclonal as defined by their exclusive expression of either kappa or lambda light chain mRNA, and that the same type of light chain mRNA is expressed in both bone marrow plasma cells and blood B cells. These abnormal tumour-related circulating B cells express high densities of CD11b, a beta 2-integrin, which is expressed in a conformationally active state as defined by reactivity with monoclonal antibody 7E3. Normal peripheral blood B cells which do not bear CD11b acquire a high density after stimulation with pokeweed mitogen (PWM). At day 4 of culture, the expression of CD11b on normal CD19+ B cells was nearly comparable to that of the circulating myeloma late stage B cells. After PWM stimulation of circulating myeloma B cells the expression of CD11b was gradually lost during 4 days of culture, suggesting that its expression is dynamically regulated. Two patients with no phenotypically abnormal B cells in their blood at diagnosis acquired a large subset of CD11b+ B cells 4 weeks after initiation of chemotherapy. In most patients, a subset of the circulating myeloma B cells express a low density of CD5. The proportion of CD19+ B cells in the bone marrow expressing CD11b was much reduced compared with peripheral blood B cells, and CD11b was not detectable on plasma cells in the bone marrow, suggesting a sequential relationship of the B-cell subsets detected in our population of patients, involving gradual loss of CD11b concurrent with the loss of CD19 during B lineage differentiation. These cells appear to represent a continuously differentiating monoclonal B lineage culminating in the CD11b- plasma cell entrenched in the bone marrow. We speculate that the expression of conformationally active CD11b on the abnormal B cells in peripheral blood mononuclear cells of myeloma patients facilitates transendothelial migration of circulating myeloma B cells to the bone marrow."} {"id": "PMID:1281336", "title": "Complement receptor type 2 mediates infection of the human CD4-negative Raji B-cell line with opsonized HIV.", "content": "Opsonization of the HTLV-RF and HTLV-IIIB strains of HIV-1 with normal human HIV seronegative serum under conditions that allow complement activation resulted in the productive infection of cells of the Raji B lymphoblastoid cell line. Under the same experimental conditions, no infection of Raji cells was observed with unopsonized virus. Infection of Raji cells with complement-opsonized HIV-1 was totally suppressed by preblocking the function of CR2 (the C3dg receptor, CD21) on the cells with a monoclonal anti-CR2 antibody cross-linked with rabbit F(ab')2 anti-mouse immunoglobulin antibodies. Infection of Raji cells occurred independently of CD4 since the cells lacked the expression of CD4 antigen and of CD4 transcripts. Thus, Raji cells may be infected with complement-opsonized HIV independently of CD4 and in the absence of antibodies. By mediating and/or enhancing HIV infection, complement and complement receptors contribute to extend the range of target cells to the virus and may increase infection in patients with a low viral load.", "contents": "Complement receptor type 2 mediates infection of the human CD4-negative Raji B-cell line with opsonized HIV. Opsonization of the HTLV-RF and HTLV-IIIB strains of HIV-1 with normal human HIV seronegative serum under conditions that allow complement activation resulted in the productive infection of cells of the Raji B lymphoblastoid cell line. Under the same experimental conditions, no infection of Raji cells was observed with unopsonized virus. Infection of Raji cells with complement-opsonized HIV-1 was totally suppressed by preblocking the function of CR2 (the C3dg receptor, CD21) on the cells with a monoclonal anti-CR2 antibody cross-linked with rabbit F(ab')2 anti-mouse immunoglobulin antibodies. Infection of Raji cells occurred independently of CD4 since the cells lacked the expression of CD4 antigen and of CD4 transcripts. Thus, Raji cells may be infected with complement-opsonized HIV independently of CD4 and in the absence of antibodies. By mediating and/or enhancing HIV infection, complement and complement receptors contribute to extend the range of target cells to the virus and may increase infection in patients with a low viral load."} {"id": "PMID:1281337", "title": "Visualizing cells in three dimensions using confocal microscopy, image reconstruction and isosurface rendering: application to glial cells in mouse central nervous system.", "content": "This paper describes a general method for visualizing individual cells in intact tissue in three dimensions. The method involves immunostaining intact tissue to label specific cells, \"optical sectioning\" the stained tissue by laser scanning confocal microscopy, computationally reconstructing a three dimensional image data set from the digitized confocal optical sections, delineating isosurfaces of specific intensity within the reconstructed image by a \"marching cubes\" algorithm to generate polygon meshes defining boundaries of cells, and displaying individual cells, identified as three dimensional objects enclosed by contiguous polygon meshes, using computer graphics techniques. Each of the components of this method has been described previously in conjunction with other applications. However the combination of these techniques to visualize a variety of different individual cell types in three dimensions in intact tissue represents a new approach. To illustrate the application of this method, we have visualized three different glial cell types in mouse CNS tissue. Oligodendrocytes, specifically stained with antibody to myelin basic protein, were used as an example of cells labelled with an internal membrane antigen. Astrocytes, specifically stained with antibody to glial fibrillary acidic protein, were used as an example of cells labelled with a cytoplasmic antigen. Microglia, specifically stained with Mac.1 antibody, were used as an example of cells labelled with an external membrane antigen. The images that are generated contain remarkably detailed volumetric and textural information that is not obtainable by conventional imaging techniques.", "contents": "Visualizing cells in three dimensions using confocal microscopy, image reconstruction and isosurface rendering: application to glial cells in mouse central nervous system. This paper describes a general method for visualizing individual cells in intact tissue in three dimensions. The method involves immunostaining intact tissue to label specific cells, \"optical sectioning\" the stained tissue by laser scanning confocal microscopy, computationally reconstructing a three dimensional image data set from the digitized confocal optical sections, delineating isosurfaces of specific intensity within the reconstructed image by a \"marching cubes\" algorithm to generate polygon meshes defining boundaries of cells, and displaying individual cells, identified as three dimensional objects enclosed by contiguous polygon meshes, using computer graphics techniques. Each of the components of this method has been described previously in conjunction with other applications. However the combination of these techniques to visualize a variety of different individual cell types in three dimensions in intact tissue represents a new approach. To illustrate the application of this method, we have visualized three different glial cell types in mouse CNS tissue. Oligodendrocytes, specifically stained with antibody to myelin basic protein, were used as an example of cells labelled with an internal membrane antigen. Astrocytes, specifically stained with antibody to glial fibrillary acidic protein, were used as an example of cells labelled with a cytoplasmic antigen. Microglia, specifically stained with Mac.1 antibody, were used as an example of cells labelled with an external membrane antigen. The images that are generated contain remarkably detailed volumetric and textural information that is not obtainable by conventional imaging techniques."} {"id": "PMID:1281338", "title": "[Retrospective survey of pharmacologic tolerance in the prevention of neoplastic recurrence of superficial urothelioma].", "content": "As from June 1989 all superficial bladder tumours (regardless whether treated by surgery or endoscopy) have been included in 5 different chemo, immuno or chemoimmunoprophylactic protocols of therapy against neoplastic recurrence. The protocols considered: mitomycin alone and in association with alpha 2a IFN; epirubicin alone and in association with alpha 2b IFN; immunomodulating alpha 2a IFN. The administration procedures adhered to those set down in the literature and late treatment modalities were used for the associations. The aim of the study was to perform a retrospective evaluation of the intravesical therapies regarding local and systemic tolerability to various drugs and disregarding any evaluation of drug efficacy, i.e. the percentage of patients free from recurrence. We evaluated 92 patients and a total of 1028 instillations carried out prior to June 1991. The number of patients in each protocol was: 31 on IFN; 13 on mitomycin; 24 on epirubicin; 14 on the immunomodulator plus with mitomycin; 10 on the immunomodulator associated with epirubicin. Treatment was suspended in 11/92 patients (11.9%). The highest percentage of interruptions (21.4%) was observed in the mitomycin plus IFN protocol, while the lowest (6.4%) was seen in the IFN monoprotocol. The percentage of patients who presented no side effects during prophylaxis was similar in all protocols studied (50% of patients on the two associations and 54.8% on IFN alone) with the exception of the epirubicin protocol patients who showed lower tolerance (41.6%). The number of \"irritable\" instillations in each protocol group was analyzed. The lowest number (9/162 = 5.5%) was conserved in the epirubicin plus IFN protocol, while the highest (19/108 17.5%) was seen in the mitomycin group.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Retrospective survey of pharmacologic tolerance in the prevention of neoplastic recurrence of superficial urothelioma]. As from June 1989 all superficial bladder tumours (regardless whether treated by surgery or endoscopy) have been included in 5 different chemo, immuno or chemoimmunoprophylactic protocols of therapy against neoplastic recurrence. The protocols considered: mitomycin alone and in association with alpha 2a IFN; epirubicin alone and in association with alpha 2b IFN; immunomodulating alpha 2a IFN. The administration procedures adhered to those set down in the literature and late treatment modalities were used for the associations. The aim of the study was to perform a retrospective evaluation of the intravesical therapies regarding local and systemic tolerability to various drugs and disregarding any evaluation of drug efficacy, i.e. the percentage of patients free from recurrence. We evaluated 92 patients and a total of 1028 instillations carried out prior to June 1991. The number of patients in each protocol was: 31 on IFN; 13 on mitomycin; 24 on epirubicin; 14 on the immunomodulator plus with mitomycin; 10 on the immunomodulator associated with epirubicin. Treatment was suspended in 11/92 patients (11.9%). The highest percentage of interruptions (21.4%) was observed in the mitomycin plus IFN protocol, while the lowest (6.4%) was seen in the IFN monoprotocol. The percentage of patients who presented no side effects during prophylaxis was similar in all protocols studied (50% of patients on the two associations and 54.8% on IFN alone) with the exception of the epirubicin protocol patients who showed lower tolerance (41.6%). The number of \"irritable\" instillations in each protocol group was analyzed. The lowest number (9/162 = 5.5%) was conserved in the epirubicin plus IFN protocol, while the highest (19/108 17.5%) was seen in the mitomycin group.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281339", "title": "[New methods for the evaluation of cervico-prostatic obstruction].", "content": "To study outflow obstructions Schafer (1989) has recently proposed a simplified method based on a graph derived from over 1000 pre and post-op. P/F studies. 42 patients with BPH were evaluated according to this method. 11 patients had no outlet obstruction (26%). Surprisingly, only 15 had a normal detrusor, while 27 had a weak detrusor. The second part of the study concerns 24 patients with post-prostatectomy frequency-dysuria syndrome. Only 21% of these patients showed an outlet obstruction; while 58% showed a weak detrusor as responsible for their symptoms.", "contents": "[New methods for the evaluation of cervico-prostatic obstruction]. To study outflow obstructions Schafer (1989) has recently proposed a simplified method based on a graph derived from over 1000 pre and post-op. P/F studies. 42 patients with BPH were evaluated according to this method. 11 patients had no outlet obstruction (26%). Surprisingly, only 15 had a normal detrusor, while 27 had a weak detrusor. The second part of the study concerns 24 patients with post-prostatectomy frequency-dysuria syndrome. Only 21% of these patients showed an outlet obstruction; while 58% showed a weak detrusor as responsible for their symptoms."} {"id": "PMID:1281341", "title": "Posterior decompression and stabilization for multiple metastatic tumors of the spine.", "content": "Although the value of surgical decompression and stabilization for solitary spinal metastasis is well documented, indication for surgery for advanced multiple metastatic tumors of the spine is controversial. In this study, the clinical effect of posterior decompression and stabilization was investigated in 11 patients with advanced multiple spinal metastases with unfavorable conditions. Mean blood loss during surgery was 3000 g. Disseminated intravascular coagulation occurred in three patients. Neurologic improvement was observed in nine patients. There was no neurologic deterioration due to surgery in any patients. A measure of pain relief was obtained in all patients. However, the postoperative longevity was short and the patients died 2.5 months (on average) after operation, except in cases of breast cancer. The effect of the posterior surgery on multiple spinal metastases depended on primary diseases. In cases of short life expectancy, the effect of the surgery was limited only to the short duration of neurologic improvement, pain relief, and ease of nursing care while confronted with grave surgical morbidity. In cases of long life expectancy with tumors like breast cancer, however, posterior decompression and stabilization were expected to exert long-term therapeutic effect. Therefore, the posterior surgery for multiple spinal metastases is cautiously indicated considering the nature of the primary tumor.", "contents": "Posterior decompression and stabilization for multiple metastatic tumors of the spine. Although the value of surgical decompression and stabilization for solitary spinal metastasis is well documented, indication for surgery for advanced multiple metastatic tumors of the spine is controversial. In this study, the clinical effect of posterior decompression and stabilization was investigated in 11 patients with advanced multiple spinal metastases with unfavorable conditions. Mean blood loss during surgery was 3000 g. Disseminated intravascular coagulation occurred in three patients. Neurologic improvement was observed in nine patients. There was no neurologic deterioration due to surgery in any patients. A measure of pain relief was obtained in all patients. However, the postoperative longevity was short and the patients died 2.5 months (on average) after operation, except in cases of breast cancer. The effect of the posterior surgery on multiple spinal metastases depended on primary diseases. In cases of short life expectancy, the effect of the surgery was limited only to the short duration of neurologic improvement, pain relief, and ease of nursing care while confronted with grave surgical morbidity. In cases of long life expectancy with tumors like breast cancer, however, posterior decompression and stabilization were expected to exert long-term therapeutic effect. Therefore, the posterior surgery for multiple spinal metastases is cautiously indicated considering the nature of the primary tumor."} {"id": "PMID:1281342", "title": "[Half-body irradiation. An effective palliative treatment of widespread skeletal metastases].", "content": "In a large number of cancer patients, extensive skeletal metastases or myelomatosis induce vast suffering, such as intolerable pain and local complications of neoplastic bone destruction. Analgetic drugs frequently do not yield sufficient palliation. Irradiation of local fields often has to be repeated, because of tumour growth outside previously irradiated volumes. Wide field irradiation of the lower or upper half of the body causes significant relief of pain in most patients. Adequate pretreatment handling of patients, method of irradiation, and follow-up are of marked importance to reduce side effects, and are described as they are carried out at the Department of Oncology, Haukeland Hospital.", "contents": "[Half-body irradiation. An effective palliative treatment of widespread skeletal metastases]. In a large number of cancer patients, extensive skeletal metastases or myelomatosis induce vast suffering, such as intolerable pain and local complications of neoplastic bone destruction. Analgetic drugs frequently do not yield sufficient palliation. Irradiation of local fields often has to be repeated, because of tumour growth outside previously irradiated volumes. Wide field irradiation of the lower or upper half of the body causes significant relief of pain in most patients. Adequate pretreatment handling of patients, method of irradiation, and follow-up are of marked importance to reduce side effects, and are described as they are carried out at the Department of Oncology, Haukeland Hospital."} {"id": "PMID:1281343", "title": "Subacute ethanol consumption reverses p-xylene-induced decreases in axonal transport.", "content": "Human exposure to organic solvents is often complicated by ethanol ingestion and the literature is replete with demonstrations of metabolic interactions between ethanol and organic solvents at a pharmacokinetic level. Because of the possible modulation of xylene toxicity by ethanol consumption, the present group of studies characterizes the effect of ethanol on the p-xylene-induced decrease in axonal transport in the rat optic system previously reported by our laboratory. Long-Evans, hooded, male rats were divided randomly into two groups: those receiving 10% ethanol in their drinking water and those receiving water only. These two groups were further subdivided into two groups which were either exposed by inhalation to 1600 ppm p-xylene for 6 h/day, 5 days/week for 8 exposure-days or were treated identically except that they were exposed to air while in the inhalation chambers. The ethanol-drinking rats were given ethanol 6 days prior to and on the days of the inhalation exposure. Immediately after removal from the inhalation chambers on the last exposure day, the animals were injected intraocularly with [35S]methionine and [3H]fucose to measure the synthesis and rapid axonal transport of proteins and glycoproteins, respectively, in the retinal ganglion cells. The animals were sacrificed 20 h later, and the amount of radioactivity in different areas of the retinal ganglion cells was determined by liquid scintillation counting. As in previous experiments, the xylene exposure group showed a significant reduction in axonal transport of proteins and glycoproteins, whereas the ethanol exposure alone produced no significant reductions in the transport of either proteins or glycoproteins. In the animals receiving both ethanol and xylene, however, the ethanol treatment prevented the decreased transport characteristic of the xylene only animals, i.e. in all areas of the optic projections the level of transport were similar to the level present in the control groups. These data suggest that the xylene-induced reduction in rapid axonal transport was reversed (or prevented) by subacute ethanol consumption.", "contents": "Subacute ethanol consumption reverses p-xylene-induced decreases in axonal transport. Human exposure to organic solvents is often complicated by ethanol ingestion and the literature is replete with demonstrations of metabolic interactions between ethanol and organic solvents at a pharmacokinetic level. Because of the possible modulation of xylene toxicity by ethanol consumption, the present group of studies characterizes the effect of ethanol on the p-xylene-induced decrease in axonal transport in the rat optic system previously reported by our laboratory. Long-Evans, hooded, male rats were divided randomly into two groups: those receiving 10% ethanol in their drinking water and those receiving water only. These two groups were further subdivided into two groups which were either exposed by inhalation to 1600 ppm p-xylene for 6 h/day, 5 days/week for 8 exposure-days or were treated identically except that they were exposed to air while in the inhalation chambers. The ethanol-drinking rats were given ethanol 6 days prior to and on the days of the inhalation exposure. Immediately after removal from the inhalation chambers on the last exposure day, the animals were injected intraocularly with [35S]methionine and [3H]fucose to measure the synthesis and rapid axonal transport of proteins and glycoproteins, respectively, in the retinal ganglion cells. The animals were sacrificed 20 h later, and the amount of radioactivity in different areas of the retinal ganglion cells was determined by liquid scintillation counting. As in previous experiments, the xylene exposure group showed a significant reduction in axonal transport of proteins and glycoproteins, whereas the ethanol exposure alone produced no significant reductions in the transport of either proteins or glycoproteins. In the animals receiving both ethanol and xylene, however, the ethanol treatment prevented the decreased transport characteristic of the xylene only animals, i.e. in all areas of the optic projections the level of transport were similar to the level present in the control groups. These data suggest that the xylene-induced reduction in rapid axonal transport was reversed (or prevented) by subacute ethanol consumption."} {"id": "PMID:1281344", "title": "Effects of feeding and fasting on hepatolobular distribution of glutathione and cadmium-induced hepatotoxicity.", "content": "Relationship between hepatolobular distribution profile of glutathione (GSH) and cadmium (Cd)-induced hepatotoxicity was examined in both fed and fasted rats by computerized densitometry of histochemically stained GSH in the liver sections using an image analyzer system. In fed rats, density gradient distribution of hepatolobular GSH, which was higher in the periportal region than in the perivenous one, was always observed even at a diurnally minimal concentration of GSH. This heterogeneous distribution of GSH, however, disappeared in fasted rats, even though the hepatic GSH concentration recovered to 81% of the control level in rats fasted for 48 h. In histopathological examination on livers 24 h after oral treatment of fed and fasted rats with 60 mg Cd/kg, zonal necrotic changes were observed from the perivenous to midlobular region but not in the periportal one in fed rats even at a diurnally minimal concentration of hepatic GSH. On the other hand, necrotic changes in the liver extended to the panlobular region including the periportal one in fasted rats. These necrotic changes were greater with a longer duration of fasting. These results suggest that the density gradient distribution of hepatic GSH but not the actual concentration of the compound plays an important role in protecting rats against acute hepatotoxicity of Cd.", "contents": "Effects of feeding and fasting on hepatolobular distribution of glutathione and cadmium-induced hepatotoxicity. Relationship between hepatolobular distribution profile of glutathione (GSH) and cadmium (Cd)-induced hepatotoxicity was examined in both fed and fasted rats by computerized densitometry of histochemically stained GSH in the liver sections using an image analyzer system. In fed rats, density gradient distribution of hepatolobular GSH, which was higher in the periportal region than in the perivenous one, was always observed even at a diurnally minimal concentration of GSH. This heterogeneous distribution of GSH, however, disappeared in fasted rats, even though the hepatic GSH concentration recovered to 81% of the control level in rats fasted for 48 h. In histopathological examination on livers 24 h after oral treatment of fed and fasted rats with 60 mg Cd/kg, zonal necrotic changes were observed from the perivenous to midlobular region but not in the periportal one in fed rats even at a diurnally minimal concentration of hepatic GSH. On the other hand, necrotic changes in the liver extended to the panlobular region including the periportal one in fasted rats. These necrotic changes were greater with a longer duration of fasting. These results suggest that the density gradient distribution of hepatic GSH but not the actual concentration of the compound plays an important role in protecting rats against acute hepatotoxicity of Cd."} {"id": "PMID:1281345", "title": "Evaluation of surfactant cytotoxicity potential by primary cultures of ocular tissues: I. Characterization of rabbit corneal epithelial cells and initial injury and delayed toxicity studies.", "content": "This investigation was undertaken to develop cytotoxicity assay systems using primary cultures of rabbit corneal epithelial cells as an experimental model to evaluate oculotoxic agents and the ability of these in vitro assay systems to predict irritancy potential and delayed toxicity. We have characterized the epithelial nature of the cultures by identifying keratins with antikeratin antibodies (AE1/AE3) and by demonstrating metabolic enzymes important to the integrity of the cells: lactate dehydrogenase, glucose 6-phosphate dehydrogenase and aldolase. Eight surfactants were compared and ranked according to their cytotoxic potential. We evaluated cytotoxicity by measuring leakage of the cytosolic enzyme, lactate dehydrogenase, into the medium, by making morphological observations and by assessing lysosomal neutral red uptake and mitochondrial 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction. The cells were treated for 1 h with the surfactants and the possibility of delayed toxicity was evaluated 24 h after removal of the surfactant. The cytotoxicity of the different types of surfactants as shown by all the tests was cationic > anionic = amphoteric > non-ionic. Triton X-100, a non-ionic surfactant but a severe irritant, had a ranking similar to anionic surfactants. The in vitro rankings corresponded well to reported in vivo Draize rabbit eye test data. The 24-h test for lactate dehydrogenase leakage showed that mild and non-irritating surfactants did not demonstrate any subsequent damage after a 1-h exposure, but the extreme and severe surfactants continued to show further damage after the 1-h exposure. These in vitro findings were similar to reported in vivo results. The neutral red and MTT tests did not adequately predict the prolonged toxicity of the more irritating surfactants, as was demonstrated by the lactate dehydrogenase leakage test. We conclude that in vitro cytotoxicity assays using primary cultures of rabbit corneal epithelial cells may be used to rank the cytotoxic potential of surfactants, but only the lactate dehydrogenase leakage test was able to assess prolonged cell injury.", "contents": "Evaluation of surfactant cytotoxicity potential by primary cultures of ocular tissues: I. Characterization of rabbit corneal epithelial cells and initial injury and delayed toxicity studies. This investigation was undertaken to develop cytotoxicity assay systems using primary cultures of rabbit corneal epithelial cells as an experimental model to evaluate oculotoxic agents and the ability of these in vitro assay systems to predict irritancy potential and delayed toxicity. We have characterized the epithelial nature of the cultures by identifying keratins with antikeratin antibodies (AE1/AE3) and by demonstrating metabolic enzymes important to the integrity of the cells: lactate dehydrogenase, glucose 6-phosphate dehydrogenase and aldolase. Eight surfactants were compared and ranked according to their cytotoxic potential. We evaluated cytotoxicity by measuring leakage of the cytosolic enzyme, lactate dehydrogenase, into the medium, by making morphological observations and by assessing lysosomal neutral red uptake and mitochondrial 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) reduction. The cells were treated for 1 h with the surfactants and the possibility of delayed toxicity was evaluated 24 h after removal of the surfactant. The cytotoxicity of the different types of surfactants as shown by all the tests was cationic > anionic = amphoteric > non-ionic. Triton X-100, a non-ionic surfactant but a severe irritant, had a ranking similar to anionic surfactants. The in vitro rankings corresponded well to reported in vivo Draize rabbit eye test data. The 24-h test for lactate dehydrogenase leakage showed that mild and non-irritating surfactants did not demonstrate any subsequent damage after a 1-h exposure, but the extreme and severe surfactants continued to show further damage after the 1-h exposure. These in vitro findings were similar to reported in vivo results. The neutral red and MTT tests did not adequately predict the prolonged toxicity of the more irritating surfactants, as was demonstrated by the lactate dehydrogenase leakage test. We conclude that in vitro cytotoxicity assays using primary cultures of rabbit corneal epithelial cells may be used to rank the cytotoxic potential of surfactants, but only the lactate dehydrogenase leakage test was able to assess prolonged cell injury."} {"id": "PMID:1281346", "title": "Differences in alpha 2u-globulins increased in male rat kidneys following treatment with several alpha 2u-globulin accumulating agents: cystein protease(s) play(s) an important role in production of kidney-type-alpha 2u-globulin.", "content": "Effects of alpha 2u-globulin accumulating agents on alpha 2u-globulins in rat kidneys were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis. Treatment of male animals with decalin (150 mg/kg), 2,2,4-trimethylpentane (50 mg/kg), isophorone (150 mg/kg), d-limonene (150 mg/kg) or 1,4-dichlorobenzene (150 mg/kg) by gavage for 14 consecutive days in each case resulted in a marked intensification of a protein band corresponding to kidney-type-alpha 2u-globulin, with a molecular mass calculated to be approximately 16 kDa. However, intraperitoneal treatment with leupeptin and E-64 (two times 0.07 mmol/kg, for each), well known cystein protease inhibitors, while only slightly increasing this kidney-type-alpha 2u-globulin band, caused the intensification of a approximately 19-kDa molecular mass protein band which was revealed to be a native-type-alpha 2u-globulin by SDS-PAGE and immunoblotting. These results indicated that at least two types of alpha 2u-globulin can be increased in male rat kidney by chemical treatment. Moreover, cystein protease(s) appear(s) to play an important role in the degradation of alpha 2u-globulin and particularly in the conversion of native-type-alpha 2u-globulin to kidney-type-alpha 2u-globulin in rat kidneys.", "contents": "Differences in alpha 2u-globulins increased in male rat kidneys following treatment with several alpha 2u-globulin accumulating agents: cystein protease(s) play(s) an important role in production of kidney-type-alpha 2u-globulin. Effects of alpha 2u-globulin accumulating agents on alpha 2u-globulins in rat kidneys were examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis. Treatment of male animals with decalin (150 mg/kg), 2,2,4-trimethylpentane (50 mg/kg), isophorone (150 mg/kg), d-limonene (150 mg/kg) or 1,4-dichlorobenzene (150 mg/kg) by gavage for 14 consecutive days in each case resulted in a marked intensification of a protein band corresponding to kidney-type-alpha 2u-globulin, with a molecular mass calculated to be approximately 16 kDa. However, intraperitoneal treatment with leupeptin and E-64 (two times 0.07 mmol/kg, for each), well known cystein protease inhibitors, while only slightly increasing this kidney-type-alpha 2u-globulin band, caused the intensification of a approximately 19-kDa molecular mass protein band which was revealed to be a native-type-alpha 2u-globulin by SDS-PAGE and immunoblotting. These results indicated that at least two types of alpha 2u-globulin can be increased in male rat kidney by chemical treatment. Moreover, cystein protease(s) appear(s) to play an important role in the degradation of alpha 2u-globulin and particularly in the conversion of native-type-alpha 2u-globulin to kidney-type-alpha 2u-globulin in rat kidneys."} {"id": "PMID:1281347", "title": "Single neurone models: oversimple, complex and reduced.", "content": "The single neurone stands in the midst of a controversy among modelers. Some believe that its details are functionally superfluous when the neurone operates in a large network, and very simple models can be used to represent the input/output characteristics of neurones. Others claim that the unique morphology and electrical properties of neurones do play an important role. Complicated models of neurones are developed to reveal how the various kinds of 'neurone-ware' (dendrites, spines, axons, membrane channels and synapses) create a computationally powerful unit. Various models are discussed, including new carefully reduced models that retain essential features of more complex models. Such intermediate models will play a central role in our efforts to understand information processing in large neuronal networks.", "contents": "Single neurone models: oversimple, complex and reduced. The single neurone stands in the midst of a controversy among modelers. Some believe that its details are functionally superfluous when the neurone operates in a large network, and very simple models can be used to represent the input/output characteristics of neurones. Others claim that the unique morphology and electrical properties of neurones do play an important role. Complicated models of neurones are developed to reveal how the various kinds of 'neurone-ware' (dendrites, spines, axons, membrane channels and synapses) create a computationally powerful unit. Various models are discussed, including new carefully reduced models that retain essential features of more complex models. Such intermediate models will play a central role in our efforts to understand information processing in large neuronal networks."} {"id": "PMID:1281348", "title": "Reconstruction of neuronal networks in culture.", "content": "Since the 1960s, the large neurones of some invertebrates have been exploited in attempts to define the neural circuits that underlie simple behaviours. Even in the relatively 'simple' nervous systems of these animals, it is often difficult to study individual synaptic connections in detail and to rule out involvement of unidentified neurones. These limitations have been overcome by reconstruction of partial circuits of identified neurones in cell culture. This approach has provided opportunities to examine the function of small neuronal circuits in a manner that is unapproachable in the intact nervous system.", "contents": "Reconstruction of neuronal networks in culture. Since the 1960s, the large neurones of some invertebrates have been exploited in attempts to define the neural circuits that underlie simple behaviours. Even in the relatively 'simple' nervous systems of these animals, it is often difficult to study individual synaptic connections in detail and to rule out involvement of unidentified neurones. These limitations have been overcome by reconstruction of partial circuits of identified neurones in cell culture. This approach has provided opportunities to examine the function of small neuronal circuits in a manner that is unapproachable in the intact nervous system."} {"id": "PMID:1281349", "title": "Reliability and information transmission in spiking neurons.", "content": "Spiking neurons encode continuous, time-varying signals in sequences of identical action potentials. Relatively simple algorithms allow one to 'decode' this neural representation of sensory data to estimate the input signals. Decoding experiments provide a quantitative characterization of information transmission and computational reliability under real-time conditions. The results of these studies show that neural coding and computation in several systems approach fundamental physical and informational theoretic limits to performance.", "contents": "Reliability and information transmission in spiking neurons. Spiking neurons encode continuous, time-varying signals in sequences of identical action potentials. Relatively simple algorithms allow one to 'decode' this neural representation of sensory data to estimate the input signals. Decoding experiments provide a quantitative characterization of information transmission and computational reliability under real-time conditions. The results of these studies show that neural coding and computation in several systems approach fundamental physical and informational theoretic limits to performance."} {"id": "PMID:1281350", "title": "Modelling of intersegmental coordination in the lamprey central pattern generator for locomotion.", "content": "Rhythmic motor activity requires coordination of different muscles or muscle groups so that they are all active with the same cycle duration and appropriate phase relationships. The neural mechanisms for such phase coupling in vertebrate locomotion are not known. Swimming in the lamprey is accomplished by the generation of a travelling wave of body curvature in which the phase coupling between segments is so controlled as to give approximately one full wavelength on the body at any swimming speed. This article reviews work that has combined mathematical analysis, biological experimentation and computer simulation to provide a conceptual framework within which intersegmental coordination can be investigated. Evidence is provided to suggest that in the lamprey, ascending coupling is dominant over descending coupling and controls the intersegmental phase lag during locomotion. The significance of long-range intersegmental coupling is also discussed.", "contents": "Modelling of intersegmental coordination in the lamprey central pattern generator for locomotion. Rhythmic motor activity requires coordination of different muscles or muscle groups so that they are all active with the same cycle duration and appropriate phase relationships. The neural mechanisms for such phase coupling in vertebrate locomotion are not known. Swimming in the lamprey is accomplished by the generation of a travelling wave of body curvature in which the phase coupling between segments is so controlled as to give approximately one full wavelength on the body at any swimming speed. This article reviews work that has combined mathematical analysis, biological experimentation and computer simulation to provide a conceptual framework within which intersegmental coordination can be investigated. Evidence is provided to suggest that in the lamprey, ascending coupling is dominant over descending coupling and controls the intersegmental phase lag during locomotion. The significance of long-range intersegmental coupling is also discussed."} {"id": "PMID:1281351", "title": "Motor-pattern-generating networks in invertebrates: modeling our way toward understanding.", "content": "Motor-pattern-generating networks in invertebrates have been the objects of intensive study to determine the origin and modulation of rhythmic neural activity. In some pattern generators, intrinsically bursting neurons drive activity throughout the network. In most pattern generators, however, rhythmicity arises from the interplay between intrinsic membrane properties and synaptic interaction. Reciprocal inhibitory synapses between neurons are thought to be crucial for generating oscillation in these networks, but a fundamental understanding of how such network oscillators work remains elusive. Progress towards this goal has come from attempts to combine computational modeling approaches with conventional physiological analysis.", "contents": "Motor-pattern-generating networks in invertebrates: modeling our way toward understanding. Motor-pattern-generating networks in invertebrates have been the objects of intensive study to determine the origin and modulation of rhythmic neural activity. In some pattern generators, intrinsically bursting neurons drive activity throughout the network. In most pattern generators, however, rhythmicity arises from the interplay between intrinsic membrane properties and synaptic interaction. Reciprocal inhibitory synapses between neurons are thought to be crucial for generating oscillation in these networks, but a fundamental understanding of how such network oscillators work remains elusive. Progress towards this goal has come from attempts to combine computational modeling approaches with conventional physiological analysis."} {"id": "PMID:1281352", "title": "The cerebellum and VOR/OKR learning models.", "content": "Although one particular model of the cerebellum, as proposed by Marr and Albus, provides a formal framework for understanding how heterosynaptic plasticity of Purkinje cells might be used for motor learning, the physiological details remain largely an engima. Developments in computational neuroscience and artificial neural networks applied to real control problems are essential to understand fully how workspace errors associated with movement performances can be converted into motor-command errors, and how these errors can then be used as one kind of synaptic input by motor-learning algorithms that are based on biologically plausible rules involving heterosynaptic plasticity. These developments, as well as recent advances in the study of cellular mechanisms of synaptic plasticity, form the basis for the detailed computational models of cerebellar motor learning that have been proposed. These models provide hints toward resolving a long-standing controversy in the oculomotor literature regarding the sites of adaptive changes in the vestibuloocular reflex (VOR) and the optokinetic eye movement response (OKR), and suggest new experiments to elucidate general mechanisms of sensory motor learning.", "contents": "The cerebellum and VOR/OKR learning models. Although one particular model of the cerebellum, as proposed by Marr and Albus, provides a formal framework for understanding how heterosynaptic plasticity of Purkinje cells might be used for motor learning, the physiological details remain largely an engima. Developments in computational neuroscience and artificial neural networks applied to real control problems are essential to understand fully how workspace errors associated with movement performances can be converted into motor-command errors, and how these errors can then be used as one kind of synaptic input by motor-learning algorithms that are based on biologically plausible rules involving heterosynaptic plasticity. These developments, as well as recent advances in the study of cellular mechanisms of synaptic plasticity, form the basis for the detailed computational models of cerebellar motor learning that have been proposed. These models provide hints toward resolving a long-standing controversy in the oculomotor literature regarding the sites of adaptive changes in the vestibuloocular reflex (VOR) and the optokinetic eye movement response (OKR), and suggest new experiments to elucidate general mechanisms of sensory motor learning."} {"id": "PMID:1281353", "title": "Rallpacks: a set of benchmarks for neuronal simulators.", "content": "The field of computational neurobiology has advanced to the point where there are several general-purpose simulators to choose from. These cater to various niches in the world of realistic neuronal models, which range from the molecular level to descriptions of entire sensory modalities. In addition, there are numerous custom-designed simulations, adaptations of electrical circuit simulators, and other specific implementations of neurobiological models. As a first step towards evaluating this disparate set of simulators and simulations, and towards establishing standards for comparisons of speed and accuracy, we describe a set of benchmarks. These have been given the name 'Rallpacks' in honor of Wilfrid Rall, who pioneered the study of neuronal systems through analytical and numerical techniques.", "contents": "Rallpacks: a set of benchmarks for neuronal simulators. The field of computational neurobiology has advanced to the point where there are several general-purpose simulators to choose from. These cater to various niches in the world of realistic neuronal models, which range from the molecular level to descriptions of entire sensory modalities. In addition, there are numerous custom-designed simulations, adaptations of electrical circuit simulators, and other specific implementations of neurobiological models. As a first step towards evaluating this disparate set of simulators and simulations, and towards establishing standards for comparisons of speed and accuracy, we describe a set of benchmarks. These have been given the name 'Rallpacks' in honor of Wilfrid Rall, who pioneered the study of neuronal systems through analytical and numerical techniques."} {"id": "PMID:1281354", "title": "Experimentalists and modelers: can we all just get along?", "content": "How can the interaction between theoretical neuroscientists and their experimental counterparts be improved? This article discusses a number of suggestions relating to the presentation of data in experimental studies. In particular, published data should account for the diversity of response properties encountered, rather than concentrating on the 'representative' response, as well as emphasizing the stochastic nature of neurons by routinely including raw, unprocessed data from individual trials, which show the degree of variability prior to averaging.", "contents": "Experimentalists and modelers: can we all just get along? How can the interaction between theoretical neuroscientists and their experimental counterparts be improved? This article discusses a number of suggestions relating to the presentation of data in experimental studies. In particular, published data should account for the diversity of response properties encountered, rather than concentrating on the 'representative' response, as well as emphasizing the stochastic nature of neurons by routinely including raw, unprocessed data from individual trials, which show the degree of variability prior to averaging."} {"id": "PMID:1281355", "title": "[Immunoglobin-binding proteins in human placenta].", "content": "Phenomena of the binding of poor-soluble placenta proteins (PSPP) with pregnant women sera IgG as well as placenta blood IgG were studied. PSPP were extracted from the placenta tissue, washed out from soluble proteins, by the use of 3M KCl solution containing 0.005 M PMSF. PSPP were separated by the use of two-dimensional isoelectrofocusing and SDS-PAG electrophoresis and more than 30 different polypeptides were visualized. Having used various ELISA procedures with pregnant women sera IgG, placenta blood IgG as well as its Fab and Fc-fragments we have shown that both the receptor-type and the antigen-antibody-like interaction of PSPP took place. Both the polypeptide compositions and the isoelectrofocusing points ranges of the antigen-antibody-like interacting IgG-binding PSPP were determined by the use of the peroxidase conjugated Fab-fragments of the placenta blood IgG.", "contents": "[Immunoglobin-binding proteins in human placenta]. Phenomena of the binding of poor-soluble placenta proteins (PSPP) with pregnant women sera IgG as well as placenta blood IgG were studied. PSPP were extracted from the placenta tissue, washed out from soluble proteins, by the use of 3M KCl solution containing 0.005 M PMSF. PSPP were separated by the use of two-dimensional isoelectrofocusing and SDS-PAG electrophoresis and more than 30 different polypeptides were visualized. Having used various ELISA procedures with pregnant women sera IgG, placenta blood IgG as well as its Fab and Fc-fragments we have shown that both the receptor-type and the antigen-antibody-like interaction of PSPP took place. Both the polypeptide compositions and the isoelectrofocusing points ranges of the antigen-antibody-like interacting IgG-binding PSPP were determined by the use of the peroxidase conjugated Fab-fragments of the placenta blood IgG."} {"id": "PMID:1281356", "title": "[Escherichia coli ribosomes having peptidyl-tRNA and deacylated tRNA at the A- and P-sites, respectively, may not be competent in translocation].", "content": "Ribosomes can have two states at 0 degree C: competent and noncompetent in translocation. In both states poly(U)-programmed ribosomes bind phenylalanyl-tRNA to A and P sites and form peptide bond. Elongation factor G promotes fast translocation in competent ribosomes and makes them noncompetent ones. Initial correlation between competent and noncompetent ribosomes is 2:1. Addition of deacylated tRNA does not influence phenomenon described as well as thermal reactivation of the ribosomes before beginning of the experiments. The possibility of deacylated tRNA translocation is shown. The translocation does not occurred provided that at least one of the ribosome sites is filled with shortened tRNA analog (tRNA with truncated CCA-end or tRNA anticodon arm).", "contents": "[Escherichia coli ribosomes having peptidyl-tRNA and deacylated tRNA at the A- and P-sites, respectively, may not be competent in translocation]. Ribosomes can have two states at 0 degree C: competent and noncompetent in translocation. In both states poly(U)-programmed ribosomes bind phenylalanyl-tRNA to A and P sites and form peptide bond. Elongation factor G promotes fast translocation in competent ribosomes and makes them noncompetent ones. Initial correlation between competent and noncompetent ribosomes is 2:1. Addition of deacylated tRNA does not influence phenomenon described as well as thermal reactivation of the ribosomes before beginning of the experiments. The possibility of deacylated tRNA translocation is shown. The translocation does not occurred provided that at least one of the ribosome sites is filled with shortened tRNA analog (tRNA with truncated CCA-end or tRNA anticodon arm)."} {"id": "PMID:1281359", "title": "[Imaging and functional parameters in diagnosis of obstructive nephropathy].", "content": "Obstruction of the kidney leads to terminal kidney failure within a few years. Therefore, early recognition of such obstruction is of importance. Non-invasive diagnostic ultrasound examination now allows intrauterine visualization of a suspected obstruction. However, the implications of such a dilated ureteral pelvic system are obscure. Whether there is obstruction or dilatation can only be evaluated postnatally by a nuclear technique. The aim of our study was to measure the recovery of kidney function. We investigated 13 kidneys of 9 newborns or small infants (up to 2 years). The follow-up was continuous for up to 29 days. The parameters were: urine output (24-h clearance), glomerular filtration rate, fractional excretion of sodium and potassium, free water clearance, total protein excretion, albumin and alpha 1 microglobulin excretion. The urine output fell from 0.3 to 0.12 ml/min within 14 days after relief of obstruction. The glomerular filtration rate rose from nearly 30 ml/min to about 50 ml/min within a week. The fractional excretion of sodium and potassium indicated recovery of the proximal tubli. The fractional sodium excretion fell below 1% within 4 days. The free water clearance reflects the concentrating ability of the kidney, and in kidneys from newborns it had only positive values, while in kidneys of children older than 6 months there were also negative values. The protein excretion and the albuminuria showed recovery of the glomerular as well as the tubular system.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Imaging and functional parameters in diagnosis of obstructive nephropathy]. Obstruction of the kidney leads to terminal kidney failure within a few years. Therefore, early recognition of such obstruction is of importance. Non-invasive diagnostic ultrasound examination now allows intrauterine visualization of a suspected obstruction. However, the implications of such a dilated ureteral pelvic system are obscure. Whether there is obstruction or dilatation can only be evaluated postnatally by a nuclear technique. The aim of our study was to measure the recovery of kidney function. We investigated 13 kidneys of 9 newborns or small infants (up to 2 years). The follow-up was continuous for up to 29 days. The parameters were: urine output (24-h clearance), glomerular filtration rate, fractional excretion of sodium and potassium, free water clearance, total protein excretion, albumin and alpha 1 microglobulin excretion. The urine output fell from 0.3 to 0.12 ml/min within 14 days after relief of obstruction. The glomerular filtration rate rose from nearly 30 ml/min to about 50 ml/min within a week. The fractional excretion of sodium and potassium indicated recovery of the proximal tubli. The fractional sodium excretion fell below 1% within 4 days. The free water clearance reflects the concentrating ability of the kidney, and in kidneys from newborns it had only positive values, while in kidneys of children older than 6 months there were also negative values. The protein excretion and the albuminuria showed recovery of the glomerular as well as the tubular system.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281360", "title": "[Urethral stricture after TURP and transvesical prostatectomy].", "content": "In an attempt to elucidate factors predisposing to the occurrence of urethral stricture after transurethral resection of the prostate, we performed a prospective follow-up of 178 patients over 12-20 months. We took account of 11 factors that we considered important. Urethral strictures developed in 14.04% of the patients. The resection operations were carried out by five different surgeons, who had different rates of stricture. The only one of the 11 factors studied that was found to involve a statistically significant risk was the presence of an indwelling catheter for more than 3 days. No other factor influenced the result. This patient group was compared with a group of 73 patients followed up for 12-60 months following transvesical prostatectomy. In this group only one stricture (1.36% incidence rate) was observed retrospectively. It seems that urethral ischaemia might increase the risk of urethral stricture. Urethral injuries are considerably less frequent with open prostatectomy. Therefore, we recommend transvesical prostatectomy for pronounced prostatic hyperplasias.", "contents": "[Urethral stricture after TURP and transvesical prostatectomy]. In an attempt to elucidate factors predisposing to the occurrence of urethral stricture after transurethral resection of the prostate, we performed a prospective follow-up of 178 patients over 12-20 months. We took account of 11 factors that we considered important. Urethral strictures developed in 14.04% of the patients. The resection operations were carried out by five different surgeons, who had different rates of stricture. The only one of the 11 factors studied that was found to involve a statistically significant risk was the presence of an indwelling catheter for more than 3 days. No other factor influenced the result. This patient group was compared with a group of 73 patients followed up for 12-60 months following transvesical prostatectomy. In this group only one stricture (1.36% incidence rate) was observed retrospectively. It seems that urethral ischaemia might increase the risk of urethral stricture. Urethral injuries are considerably less frequent with open prostatectomy. Therefore, we recommend transvesical prostatectomy for pronounced prostatic hyperplasias."} {"id": "PMID:1281357", "title": "[Effect of ecdysterone on the metabolism of purine and pyrimidine nucleotides in chicken tissues].", "content": "Hormonal amounts (10(-7) M) of ecdysterone phytoecdysteroid have been studied for their effect on the metabolic processes in the chicken tissues. Changes in the blood serum parameters which characterize the state of the integral systems of mineral, lipid, protein and nucleotide metabolism as well as the dynamics of metabolism of nucleic acids and their precursors--purine and pyrimidine nucleotides in the tissues with actively functioning protein-synthesizing system prove that the biological effect of ecdysterone after its introduction to the bird organism manifests both in the non-genome early phase of the action (0-1 h) and in the late genome phase (24-72 h), i.e. in analogy to the time of response to the introduction of classical steroid hormones. It is supposed that polyfunctional early effect of ecdysterone is mediated by its action on one of universal transmembrane signal systems of the cells--adenylate cyclase or polyphosphoinosite one, while the presence of the expressed changes in metabolism of nucleic acids in the late phase unambiguously indicate to its action in the bird organism as that of a typical steroid hormone.", "contents": "[Effect of ecdysterone on the metabolism of purine and pyrimidine nucleotides in chicken tissues]. Hormonal amounts (10(-7) M) of ecdysterone phytoecdysteroid have been studied for their effect on the metabolic processes in the chicken tissues. Changes in the blood serum parameters which characterize the state of the integral systems of mineral, lipid, protein and nucleotide metabolism as well as the dynamics of metabolism of nucleic acids and their precursors--purine and pyrimidine nucleotides in the tissues with actively functioning protein-synthesizing system prove that the biological effect of ecdysterone after its introduction to the bird organism manifests both in the non-genome early phase of the action (0-1 h) and in the late genome phase (24-72 h), i.e. in analogy to the time of response to the introduction of classical steroid hormones. It is supposed that polyfunctional early effect of ecdysterone is mediated by its action on one of universal transmembrane signal systems of the cells--adenylate cyclase or polyphosphoinosite one, while the presence of the expressed changes in metabolism of nucleic acids in the late phase unambiguously indicate to its action in the bird organism as that of a typical steroid hormone."} {"id": "PMID:1281361", "title": "[2 cases of anencephaly in one family].", "content": "Two births of anencephalic fetuses occurred in the second and the fourth pregnancies in a family. The children born after the 1st and 3rd pregnancies were normal. Anencephaly was not associated with spina bifida, and both fetuses were female. The study failed to demonstrate the cause of the abnormality.", "contents": "[2 cases of anencephaly in one family]. Two births of anencephalic fetuses occurred in the second and the fourth pregnancies in a family. The children born after the 1st and 3rd pregnancies were normal. Anencephaly was not associated with spina bifida, and both fetuses were female. The study failed to demonstrate the cause of the abnormality."} {"id": "PMID:1281363", "title": "The endemic treponematoses: not yet eradicated.", "content": "The endemic treponematoses which comprise yaws, endemic syphilis (bejel) and pinta constitute a group of potentially disabling and disfiguring infections which primarily afflict children in tropical and subtropical areas. Foci where these diseases are now endemic have a patchy distribution and are typically confined to underprivileged communities living in remote rural areas, with little or no access to health services and removed from the mainstream of socioeconomic development. A drastic decline in the prevalence of these infections was brought about by the implementation of mass treatment campaigns with penicillin under the technical guidance of WHO and with material support from UNICEF in the 1950s and 1960s. These worldwide campaigns against the endemic treponematoses halted disease transmission in many areas and held the promise of complete eradication if intensive surveillance could be continued for some time with the increasing involvement of the basic health services. National campaigns were so successful that relatively low priority was given to the preparation of the rural health services for this new task. The failure of many countries to integrate active control measures into the functions of the rural health services led to the gradual build-up and extension of treponemal reservoirs and the resurgence of foci of increased disease transmission particularly in communities where standards of hygiene and health care had remained low. In a number of former endemic foci only low-level transmission persisted; in a few areas disease prevalence increased dramatically to reach pre-campaign levels. The lack of technical and financial resources limited the success of renewed national control activities in the most affected areas. Today, with waning interest in these diseases confined to remote, and thus silent, population groups, and a decreasing ability of health staff to identify cases, data collected by countries need to be supplemented by information from other sources in order to arrive at a more valid assessment of the situation concerning the endemic treponematoses. Central and West Africa are most severely affected by the resurgence of the endemic treponematoses. In recent years a number of countries (e.g. Ghana, C\u00f4te d'Ivoire and Mali) have launched renewed control efforts, often combining yaws or endemic syphilis control with other public health programmes. In Central Africa itinerant pygmy groups are still highly affected by yaws and are an important source of infection for the sedentary population with which they come into contact. In Chad, Sudan and Ethiopia, there is some evidence of persistent foci of endemic treponematoses; the epidemiological situation in Southern Africa is not well established.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "The endemic treponematoses: not yet eradicated. The endemic treponematoses which comprise yaws, endemic syphilis (bejel) and pinta constitute a group of potentially disabling and disfiguring infections which primarily afflict children in tropical and subtropical areas. Foci where these diseases are now endemic have a patchy distribution and are typically confined to underprivileged communities living in remote rural areas, with little or no access to health services and removed from the mainstream of socioeconomic development. A drastic decline in the prevalence of these infections was brought about by the implementation of mass treatment campaigns with penicillin under the technical guidance of WHO and with material support from UNICEF in the 1950s and 1960s. These worldwide campaigns against the endemic treponematoses halted disease transmission in many areas and held the promise of complete eradication if intensive surveillance could be continued for some time with the increasing involvement of the basic health services. National campaigns were so successful that relatively low priority was given to the preparation of the rural health services for this new task. The failure of many countries to integrate active control measures into the functions of the rural health services led to the gradual build-up and extension of treponemal reservoirs and the resurgence of foci of increased disease transmission particularly in communities where standards of hygiene and health care had remained low. In a number of former endemic foci only low-level transmission persisted; in a few areas disease prevalence increased dramatically to reach pre-campaign levels. The lack of technical and financial resources limited the success of renewed national control activities in the most affected areas. Today, with waning interest in these diseases confined to remote, and thus silent, population groups, and a decreasing ability of health staff to identify cases, data collected by countries need to be supplemented by information from other sources in order to arrive at a more valid assessment of the situation concerning the endemic treponematoses. Central and West Africa are most severely affected by the resurgence of the endemic treponematoses. In recent years a number of countries (e.g. Ghana, C\u00f4te d'Ivoire and Mali) have launched renewed control efforts, often combining yaws or endemic syphilis control with other public health programmes. In Central Africa itinerant pygmy groups are still highly affected by yaws and are an important source of infection for the sedentary population with which they come into contact. In Chad, Sudan and Ethiopia, there is some evidence of persistent foci of endemic treponematoses; the epidemiological situation in Southern Africa is not well established.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281364", "title": "World malaria situation 1990. Division of Control of Tropical Diseases. World Health Organization, Geneva.", "content": "Malaria risk of varying degree exists in 99 countries or areas. However, falciparum malaria does not exist or its relative prevalence is less than 1% in 13 of these countries. Accurate information on the global incidence of malaria is difficult to obtain because reporting is particularly incomplete in areas known to be highly endemic. The global incidence of malaria is estimated to be nearly 120 million clinical cases each year, with nearly 300 million people carrying the parasite. 90% of the total number of cases reported annually to WHO are from 19 countries only. This does not include the WHO African Region where reporting of cases remains fragmentary and irregular despite improvements in recent years. Some 75% of cases are concentrated in 9 countries (in decreasing order): India, Brazil, Afghanistan, Sri Lanka, Thailand, Indonesia, Viet Nam, Cambodia and China. Furthermore, within these countries malaria is concentrated in certain areas. Of a total world population of about 5.3 billion people, 3.1 billion (59%) live in areas free of malaria (it never existed, disappeared or was eliminated by antimalaria campaigns and the malaria-free status has been maintained). 1.7 billion people (32%) live in areas where endemic malaria was considerably reduced or even eliminated but transmission was reinstated and the situation is unstable or deteriorating. These latter areas include zones with the most severe malaria problems which developed following major ecological or social changes, such as agricultural or other economic exploitation of jungle areas, sociopolitical unrest, etc.; these zones comprise only about 1% of the world population. Areas where endemic malaria remains basically unchanged, and no national antimalaria programme was ever implemented, are inhabited by 500 million people (9%), mainly in tropical Africa. Severe malaria and mortality are caused by Plasmodium falciparum which is the predominant species of malaria in tropical Africa. In the rest of the world it is far less common. WHO receives very limited and irregular reports on malaria deaths. The vast majority of malaria deaths occur in Africa; estimates vary greatly: a figure of 800,000 deaths per year in African children has been quoted in 1991 by the WHO African Region. There are indications that mortality in children has fallen in some areas because of the widespread use of antimalarials, of social development and of better education. Countries in tropical Africa are estimated to have more than 80% of all clinical cases and more than 90% of all parasite carriers.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "World malaria situation 1990. Division of Control of Tropical Diseases. World Health Organization, Geneva. Malaria risk of varying degree exists in 99 countries or areas. However, falciparum malaria does not exist or its relative prevalence is less than 1% in 13 of these countries. Accurate information on the global incidence of malaria is difficult to obtain because reporting is particularly incomplete in areas known to be highly endemic. The global incidence of malaria is estimated to be nearly 120 million clinical cases each year, with nearly 300 million people carrying the parasite. 90% of the total number of cases reported annually to WHO are from 19 countries only. This does not include the WHO African Region where reporting of cases remains fragmentary and irregular despite improvements in recent years. Some 75% of cases are concentrated in 9 countries (in decreasing order): India, Brazil, Afghanistan, Sri Lanka, Thailand, Indonesia, Viet Nam, Cambodia and China. Furthermore, within these countries malaria is concentrated in certain areas. Of a total world population of about 5.3 billion people, 3.1 billion (59%) live in areas free of malaria (it never existed, disappeared or was eliminated by antimalaria campaigns and the malaria-free status has been maintained). 1.7 billion people (32%) live in areas where endemic malaria was considerably reduced or even eliminated but transmission was reinstated and the situation is unstable or deteriorating. These latter areas include zones with the most severe malaria problems which developed following major ecological or social changes, such as agricultural or other economic exploitation of jungle areas, sociopolitical unrest, etc.; these zones comprise only about 1% of the world population. Areas where endemic malaria remains basically unchanged, and no national antimalaria programme was ever implemented, are inhabited by 500 million people (9%), mainly in tropical Africa. Severe malaria and mortality are caused by Plasmodium falciparum which is the predominant species of malaria in tropical Africa. In the rest of the world it is far less common. WHO receives very limited and irregular reports on malaria deaths. The vast majority of malaria deaths occur in Africa; estimates vary greatly: a figure of 800,000 deaths per year in African children has been quoted in 1991 by the WHO African Region. There are indications that mortality in children has fallen in some areas because of the widespread use of antimalarials, of social development and of better education. Countries in tropical Africa are estimated to have more than 80% of all clinical cases and more than 90% of all parasite carriers.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281362", "title": "Prevention of deep vein thrombosis in patients with hip fractures: low molecular weight heparin versus dextran.", "content": "A randomized open trial was undertaken to compare the antithrombotic efficacy of a low molecular weight heparin (LMWH; Sandoparin) with that of dextran 70 in patients undergoing surgery for hip fracture. One hundred thirteen patients received LMWH once daily subcutaneously at a fixed dosage while 103 patients received intravenous dextran 70. Postoperative deep vein thrombosis (DVT) was assessed by a diagnostic algorithm using the 125Iodine fibrinogen uptake test as screening and Duplex ultrasonography and/or ascending venography as confirming techniques for suspected DVT. The frequency of DVT was significantly lower in the LMWH group than in the dextran group (15.5 versus 32.6%, p less than 0.005). Proximal DVT was rare in both groups (LMWH: 2%, Dextran: 1%). Only one case of fatal fat pulmonary embolism was observed during the 10 day prophylaxis period in a patient receiving Dextran. Three cases of pulmonary embolism occurred later; one fatal event in the dextran group on day 14, and two cases in the LMWH group (one fatal and one non-fatal event) on day 14 and 17, respectively. There was no major bleeding complication in either group. We conclude that the LMWH we used is safe, was well tolerated, and has a significantly better thromboprophylactic effect than dextran 70.", "contents": "Prevention of deep vein thrombosis in patients with hip fractures: low molecular weight heparin versus dextran. A randomized open trial was undertaken to compare the antithrombotic efficacy of a low molecular weight heparin (LMWH; Sandoparin) with that of dextran 70 in patients undergoing surgery for hip fracture. One hundred thirteen patients received LMWH once daily subcutaneously at a fixed dosage while 103 patients received intravenous dextran 70. Postoperative deep vein thrombosis (DVT) was assessed by a diagnostic algorithm using the 125Iodine fibrinogen uptake test as screening and Duplex ultrasonography and/or ascending venography as confirming techniques for suspected DVT. The frequency of DVT was significantly lower in the LMWH group than in the dextran group (15.5 versus 32.6%, p less than 0.005). Proximal DVT was rare in both groups (LMWH: 2%, Dextran: 1%). Only one case of fatal fat pulmonary embolism was observed during the 10 day prophylaxis period in a patient receiving Dextran. Three cases of pulmonary embolism occurred later; one fatal event in the dextran group on day 14, and two cases in the LMWH group (one fatal and one non-fatal event) on day 14 and 17, respectively. There was no major bleeding complication in either group. We conclude that the LMWH we used is safe, was well tolerated, and has a significantly better thromboprophylactic effect than dextran 70."} {"id": "PMID:1281365", "title": "[In vitro effects of low molecular weight dextran on the surface properties of LDL].", "content": "The relative number of free amino groups on the surface of low density lipoproteins (LDL) was determined after the incubation with low molecular weight dextran (MW 40,000) in several concentrations by two different assays (fluorescamine, TNBS). A decrease of the detectable free amino groups of 40% was shown by both assays. After the incubation of lysine with dextran these changes could not be observed. These results are explained with the aggregation of LDL particles influenced by dextran.", "contents": "[In vitro effects of low molecular weight dextran on the surface properties of LDL]. The relative number of free amino groups on the surface of low density lipoproteins (LDL) was determined after the incubation with low molecular weight dextran (MW 40,000) in several concentrations by two different assays (fluorescamine, TNBS). A decrease of the detectable free amino groups of 40% was shown by both assays. After the incubation of lysine with dextran these changes could not be observed. These results are explained with the aggregation of LDL particles influenced by dextran."} {"id": "PMID:1281368", "title": "Oligodendrocytes from optic nerves subjected to long term Wallerian degeneration retain the capacity to myelinate.", "content": "It has previously been shown in the adult rat optic nerve that cells with many features of oligodendrocytes are capable of surviving for extended periods of time in the absence of axons. This is in contrast to the situation in the developing nervous system, where removal of axons leads to the failure of differentiation and to the death of oligodendrocytes. In the adult, these surviving oligodendrocytes were not typical in their appearance, and could only be identified with certainty using cell specific markers. In the present experiments, the functional capacity of these long-term quiescent cells to regenerate and myelinate was tested using the Shiverer mouse, a mutant lacking the gene for myelin basic protein (MBP), as a host animal. Fragments of optic nerve from adult rats which had been enucleated up to 2 years previously, were implanted into neonatal Shiverer mice. Four weeks later, the brains were removed and the formation of myelin investigated with antibodies to MBP, to ensure that this was of donor origin. Axons were demonstrated to have grown into the implants, and may have provided the stimulus for the production of MBP by the oligodendrocytes, which were stained positively within the implant. Myelin was demonstrated both within and adjacent to the implant. This study indicates that in the adult central nervous system, cells can survive for extended periods of time in the absence of axons, albeit in an inactive state, and are then capable of functional regeneration when placed in contact with unmyelinated axons. The origin of these cells, either from surviving oligodendrocytes which had previously myelinated the axons, or from progenitors lying within the adult nerve is unclear. The implications of these results are of importance in the further investigation of the potential for central nervous system regeneration.", "contents": "Oligodendrocytes from optic nerves subjected to long term Wallerian degeneration retain the capacity to myelinate. It has previously been shown in the adult rat optic nerve that cells with many features of oligodendrocytes are capable of surviving for extended periods of time in the absence of axons. This is in contrast to the situation in the developing nervous system, where removal of axons leads to the failure of differentiation and to the death of oligodendrocytes. In the adult, these surviving oligodendrocytes were not typical in their appearance, and could only be identified with certainty using cell specific markers. In the present experiments, the functional capacity of these long-term quiescent cells to regenerate and myelinate was tested using the Shiverer mouse, a mutant lacking the gene for myelin basic protein (MBP), as a host animal. Fragments of optic nerve from adult rats which had been enucleated up to 2 years previously, were implanted into neonatal Shiverer mice. Four weeks later, the brains were removed and the formation of myelin investigated with antibodies to MBP, to ensure that this was of donor origin. Axons were demonstrated to have grown into the implants, and may have provided the stimulus for the production of MBP by the oligodendrocytes, which were stained positively within the implant. Myelin was demonstrated both within and adjacent to the implant. This study indicates that in the adult central nervous system, cells can survive for extended periods of time in the absence of axons, albeit in an inactive state, and are then capable of functional regeneration when placed in contact with unmyelinated axons. The origin of these cells, either from surviving oligodendrocytes which had previously myelinated the axons, or from progenitors lying within the adult nerve is unclear. The implications of these results are of importance in the further investigation of the potential for central nervous system regeneration."} {"id": "PMID:1281366", "title": "[The production of autoantibodies to nerve tissue glycolipid antigens in patients with traumatic spinal cord injuries].", "content": "The production of autoantibodies (AAB) to the specific antigen of myelin-containing components of the nervous tissue galactocerebroside (GalC) was revealed in 117 patients with traumatic injuries to the spinal cord of various severity in periods of 18 months to 46 years after the injury. The degree of nervous system destruction, the type of the course of posttraumatic myelopathy, and the level of production of AAB to GalC were found interrelated. The existence of AAB provides evidence of sensitization of the immune system to nervous tissue antigens in spinal cord injury, while the level of AAB to GalC reflects the activity of the continuing destructive process due to the injuring effect of AAB under conditions of impaired permeability of the blood-brain barrier and shows the desirability of desensitization therapy.", "contents": "[The production of autoantibodies to nerve tissue glycolipid antigens in patients with traumatic spinal cord injuries]. The production of autoantibodies (AAB) to the specific antigen of myelin-containing components of the nervous tissue galactocerebroside (GalC) was revealed in 117 patients with traumatic injuries to the spinal cord of various severity in periods of 18 months to 46 years after the injury. The degree of nervous system destruction, the type of the course of posttraumatic myelopathy, and the level of production of AAB to GalC were found interrelated. The existence of AAB provides evidence of sensitization of the immune system to nervous tissue antigens in spinal cord injury, while the level of AAB to GalC reflects the activity of the continuing destructive process due to the injuring effect of AAB under conditions of impaired permeability of the blood-brain barrier and shows the desirability of desensitization therapy."} {"id": "PMID:1281369", "title": "Bradykinin stimulates Ca2+ entry via nitrendipine-sensitive Ca2+ channels in cultured human fibroblasts.", "content": "Bradykinin stimulates Ca2+ entry in cultured human fibroblasts via nitrendipine-sensitive Ca2+ channels in cultured human fibroblasts. The Ca2+ entering via this pathway does not contribute directly to the elevation of cytosolic Ca2+, but rather appears to be specifically taken up into an internal Ca2+ pool.", "contents": "Bradykinin stimulates Ca2+ entry via nitrendipine-sensitive Ca2+ channels in cultured human fibroblasts. Bradykinin stimulates Ca2+ entry in cultured human fibroblasts via nitrendipine-sensitive Ca2+ channels in cultured human fibroblasts. The Ca2+ entering via this pathway does not contribute directly to the elevation of cytosolic Ca2+, but rather appears to be specifically taken up into an internal Ca2+ pool."} {"id": "PMID:1281367", "title": "[The dynamics of the quantitative changes in neurospecific proteins in the blood of neural cancer patients].", "content": "The authors studied the effect of a neurosurgical intervention on the dynamics of quantitative changes of neurospecific proteins (NSP(--alpha 1 and alpha 2 globulins of the brain (alpha GM1, alpha GM2), L2 glycoprotein (alpha GP2), and glyofibril acid protein (GFA)--in blood of neuro-oncological patients. High background NSP values were revealed in most of the 14 examined patients for the first time. A significant increase of the amount of proteins in the blood during anesthesia and in the course or the operation was found. Deviation of values from the average statistical parameters was encountered in patients with an unfavorable outcome. The results of the study point to marked changes of the blood-brain barrier in neuro-oncological patients.", "contents": "[The dynamics of the quantitative changes in neurospecific proteins in the blood of neural cancer patients]. The authors studied the effect of a neurosurgical intervention on the dynamics of quantitative changes of neurospecific proteins (NSP(--alpha 1 and alpha 2 globulins of the brain (alpha GM1, alpha GM2), L2 glycoprotein (alpha GP2), and glyofibril acid protein (GFA)--in blood of neuro-oncological patients. High background NSP values were revealed in most of the 14 examined patients for the first time. A significant increase of the amount of proteins in the blood during anesthesia and in the course or the operation was found. Deviation of values from the average statistical parameters was encountered in patients with an unfavorable outcome. The results of the study point to marked changes of the blood-brain barrier in neuro-oncological patients."} {"id": "PMID:1281370", "title": "Kallikrein-kinin system in the angiogenesis.", "content": "Using the bioassay to investigate the presence of mediators in the angiogenesis exudate to explain its property to cause vascular permeability and fall in the blood pressure we found the presence of histamine, bradykinin, prostaglandin E2 and angiotensin in the exudate. However, the role of these mediators in the angiogenesis process needs to be investigated.", "contents": "Kallikrein-kinin system in the angiogenesis. Using the bioassay to investigate the presence of mediators in the angiogenesis exudate to explain its property to cause vascular permeability and fall in the blood pressure we found the presence of histamine, bradykinin, prostaglandin E2 and angiotensin in the exudate. However, the role of these mediators in the angiogenesis process needs to be investigated."} {"id": "PMID:1281371", "title": "The epidermal growth factor precursor in the rat kidney seems to be processed by an aprotinin sensitive proteinase.", "content": "Epidermal growth factor (EGF) is synthesized as a membrane bound precursor in the rat kidney. The precursor seems to be processed by an aprotinin sensitive proteinase. Intravenous infusion of aprotinin reduces the urinary excretion of EGF by 85% and increases the amount of renal EGF. Kidney membranes incubated at 37 degrees C release EGF and this release is inhibited by aprotinin.", "contents": "The epidermal growth factor precursor in the rat kidney seems to be processed by an aprotinin sensitive proteinase. Epidermal growth factor (EGF) is synthesized as a membrane bound precursor in the rat kidney. The precursor seems to be processed by an aprotinin sensitive proteinase. Intravenous infusion of aprotinin reduces the urinary excretion of EGF by 85% and increases the amount of renal EGF. Kidney membranes incubated at 37 degrees C release EGF and this release is inhibited by aprotinin."} {"id": "PMID:1281372", "title": "Vasoactive effects of aprotinin.", "content": "The protease inhibitor aprotinin was given a) in experimental septic shock, and b) in patients with hepatic cirrhosis and ascites, since in both conditions, activation of the plasma kallikrein-kinin system is associated with pathological systemic vasodilatation, which may trigger reflex neuroendocrine activation and renal solute retention. Given early in experimental sepsis, aprotinin maintained the arterial pressure, systemic vascular resistance (SVR), creatinine clearance and sodium excretion, all of which fell in controls. Aprotinin also blocked increases in pulmonary artery pressure and plasma renin activity (PRA). Given late in sepsis, aprotinin caused a rapid rise in arterial pressure and SVR towards baseline levels. In cirrhosis, aprotinin increased SVR in patients with low baseline values, and improved glomerular filtration rate, renal plasma flow and sodium excretion in all subjects; PRA was suppressed by aprotinin. Aprotinin reverses pathological systemic vasodilatation in these two conditions, and this is associated with a reduction in renin release and improved renal function.", "contents": "Vasoactive effects of aprotinin. The protease inhibitor aprotinin was given a) in experimental septic shock, and b) in patients with hepatic cirrhosis and ascites, since in both conditions, activation of the plasma kallikrein-kinin system is associated with pathological systemic vasodilatation, which may trigger reflex neuroendocrine activation and renal solute retention. Given early in experimental sepsis, aprotinin maintained the arterial pressure, systemic vascular resistance (SVR), creatinine clearance and sodium excretion, all of which fell in controls. Aprotinin also blocked increases in pulmonary artery pressure and plasma renin activity (PRA). Given late in sepsis, aprotinin caused a rapid rise in arterial pressure and SVR towards baseline levels. In cirrhosis, aprotinin increased SVR in patients with low baseline values, and improved glomerular filtration rate, renal plasma flow and sodium excretion in all subjects; PRA was suppressed by aprotinin. Aprotinin reverses pathological systemic vasodilatation in these two conditions, and this is associated with a reduction in renin release and improved renal function."} {"id": "PMID:1281373", "title": "Activation of the contact system in ascites from patients with gastrointestinal cancer.", "content": "Our observations indicates that the plasma contact system is activated in ascites from patients with gastrointestinal cancer: Factor XII is activated, plasma kallikrein is present in complex with the protease inhibitor alpha 2-macroglobulin, and the plasma kallikrein substrate high molecular weight kininogen, is highly degraded. Contact activation seems to take place in spite of a high level of inhibition. Activation of the contact system generates mediators, which may play a role in the accumulation of ascites.", "contents": "Activation of the contact system in ascites from patients with gastrointestinal cancer. Our observations indicates that the plasma contact system is activated in ascites from patients with gastrointestinal cancer: Factor XII is activated, plasma kallikrein is present in complex with the protease inhibitor alpha 2-macroglobulin, and the plasma kallikrein substrate high molecular weight kininogen, is highly degraded. Contact activation seems to take place in spite of a high level of inhibition. Activation of the contact system generates mediators, which may play a role in the accumulation of ascites."} {"id": "PMID:1281374", "title": "The effects of fractionated and unfractionated heparins with and without aprotinin on plasma inhibition of alpha and beta FX11a.", "content": "Chromogenic peptide substrate assays were used to compare the effects of fractionated and unfractionated heparins on plasma inhibition of alpha and beta FX11a, with and without various concentrations of aprotinin. All of the heparins reduced beta FX11a inhibition at 1 or 2U/ml. Four heparins increased alpha FX11a inhibition. Aprotinin counteracted the reduction in beta FX11a inhibition and augmented the heparin potentiation of alpha FX11a inhibition.", "contents": "The effects of fractionated and unfractionated heparins with and without aprotinin on plasma inhibition of alpha and beta FX11a. Chromogenic peptide substrate assays were used to compare the effects of fractionated and unfractionated heparins on plasma inhibition of alpha and beta FX11a, with and without various concentrations of aprotinin. All of the heparins reduced beta FX11a inhibition at 1 or 2U/ml. Four heparins increased alpha FX11a inhibition. Aprotinin counteracted the reduction in beta FX11a inhibition and augmented the heparin potentiation of alpha FX11a inhibition."} {"id": "PMID:1281375", "title": "Lack of significant unspecific effects of HOE 140 and other novel bradykinin antagonists in vitro and in vivo.", "content": "The novel, potent and long-acting bradykinin (BK) antagonists, HOE 140, compound II and compound III, slightly decreased blood pressure, but did not affect heart rate and respiration of rats. The antagonists did not cause bronchoconstriction in guinea-pigs. Neither HOE 140 nor BK released histamine from isolated perfused hindlegs of rats. The lack of significant unspecific side effects of the novel antagonists of effective doses will further increase the usefulness of these compounds for experimental and therapeutic purposes.", "contents": "Lack of significant unspecific effects of HOE 140 and other novel bradykinin antagonists in vitro and in vivo. The novel, potent and long-acting bradykinin (BK) antagonists, HOE 140, compound II and compound III, slightly decreased blood pressure, but did not affect heart rate and respiration of rats. The antagonists did not cause bronchoconstriction in guinea-pigs. Neither HOE 140 nor BK released histamine from isolated perfused hindlegs of rats. The lack of significant unspecific side effects of the novel antagonists of effective doses will further increase the usefulness of these compounds for experimental and therapeutic purposes."} {"id": "PMID:1281376", "title": "Effects of bradykinin on ion conductances in NG108-15 neuroblastoma x glioma hybrid cells recorded with patch-clamp electrodes.", "content": "Under whole-cell recording, bradykinin (BK) produced an initial outward membrane current followed by an inward current in voltage-clamped NG108-15 cells. The initial outward current was associated with a rise in intracellular Ca2+ and was accompanied by the opening of Ca(2+)-dependent K(+)-channels recorded with a cell-attached patch electrode. This current was inhibited by intracellular Mg2+. The inward current was associated with inhibition of the voltage-dependent K(+)-current IK(M). These effects accord with those previously observed in microelectrode-impaled cells, with the difference that BK produced much more pronounced and long-lasting desensitization in the patch-clamped cells.", "contents": "Effects of bradykinin on ion conductances in NG108-15 neuroblastoma x glioma hybrid cells recorded with patch-clamp electrodes. Under whole-cell recording, bradykinin (BK) produced an initial outward membrane current followed by an inward current in voltage-clamped NG108-15 cells. The initial outward current was associated with a rise in intracellular Ca2+ and was accompanied by the opening of Ca(2+)-dependent K(+)-channels recorded with a cell-attached patch electrode. This current was inhibited by intracellular Mg2+. The inward current was associated with inhibition of the voltage-dependent K(+)-current IK(M). These effects accord with those previously observed in microelectrode-impaled cells, with the difference that BK produced much more pronounced and long-lasting desensitization in the patch-clamped cells."} {"id": "PMID:1281377", "title": "Renal hyperfiltration states: relationship to kallikrein and kinins.", "content": "Animal models and humans with glomerular hyperfiltration and hyperperfusion secondary to diabetes or high protein diet show increased renal production of kallikrein and kinins. Acute aminoacid infusion or ingestion also raises GFR, RPF and urinary kinins. Treatment with aprotinin or a kinin receptor antagonist reverses or prevents hyperfiltration in these rat models.", "contents": "Renal hyperfiltration states: relationship to kallikrein and kinins. Animal models and humans with glomerular hyperfiltration and hyperperfusion secondary to diabetes or high protein diet show increased renal production of kallikrein and kinins. Acute aminoacid infusion or ingestion also raises GFR, RPF and urinary kinins. Treatment with aprotinin or a kinin receptor antagonist reverses or prevents hyperfiltration in these rat models."} {"id": "PMID:1281378", "title": "Stimulation of endothelial autacoid formation by inhibitors of angiotensin-converting enzyme.", "content": "We have investigated in human endothelial cells in culture the effects of angiotensin-converting enzyme (ACE) inhibitors on the concentration of intracellular free Ca2+ ([Ca2+]i) and the formation of nitric oxide (NO) and prostacyclin (PGI2). Enalaprilat, moexiprilat and ramiprilat similarly potentiated the increase in [Ca2+]i elicited by bradykinin and caused an increase in resting [Ca2+]i when given alone. The latter effect was long-lasting and accompanied by an increased formation of NO and PGI2. All of these effects were inhibited by the B2-kinin receptor antagonist Hoe 140, suggesting that the endogenous synthesis/release of bradykinin represents an autocrine mechanism for the stimulation of endothelial autacoid formation. Thus these findings strongly support the concept that ACE inhibitors promote local vasodilation by increasing the level of bradykinin generated in subthreshold concentrations by the endothelium.", "contents": "Stimulation of endothelial autacoid formation by inhibitors of angiotensin-converting enzyme. We have investigated in human endothelial cells in culture the effects of angiotensin-converting enzyme (ACE) inhibitors on the concentration of intracellular free Ca2+ ([Ca2+]i) and the formation of nitric oxide (NO) and prostacyclin (PGI2). Enalaprilat, moexiprilat and ramiprilat similarly potentiated the increase in [Ca2+]i elicited by bradykinin and caused an increase in resting [Ca2+]i when given alone. The latter effect was long-lasting and accompanied by an increased formation of NO and PGI2. All of these effects were inhibited by the B2-kinin receptor antagonist Hoe 140, suggesting that the endogenous synthesis/release of bradykinin represents an autocrine mechanism for the stimulation of endothelial autacoid formation. Thus these findings strongly support the concept that ACE inhibitors promote local vasodilation by increasing the level of bradykinin generated in subthreshold concentrations by the endothelium."} {"id": "PMID:1281379", "title": "Essential role of kallikrein-kinin system in suppression of blood pressure rise during the developmental stage of hypertension induced by deoxycorticosterone acetate-salt in rats.", "content": "Deoxycorticosterone acetate (DOCA)-salt hypertension was induced in Brown Norway (BN) kininogen-deficient rats (BN-Ka) and normal rats from the same strain (BN-Ki) after nephrectomy. Systolic blood pressure, which was determined by the tail-cuff method, of BN-Ki increased gradually during this treatment. In contrast, the blood pressure of mutant BN-Ka increased rapidly 2 weeks after the onset of the treatment. Urinary excretion of active kallikrein and prokallikrein increased at the same degree in rats of both strains during this treatment. Significant increase in urinary sodium excretion was observed with a tendency to increase in urine volume during the treatment in normal BN-Ki rats, whereas both parameters were essentially not increased in mutant BN-Ka rats, which could not generate urinary kinin. Aprotinin infusion by osmotic minipump to normal BN-Ki rats during the DOCA-salt treatment resulted in significant further increase in the systolic blood pressure.", "contents": "Essential role of kallikrein-kinin system in suppression of blood pressure rise during the developmental stage of hypertension induced by deoxycorticosterone acetate-salt in rats. Deoxycorticosterone acetate (DOCA)-salt hypertension was induced in Brown Norway (BN) kininogen-deficient rats (BN-Ka) and normal rats from the same strain (BN-Ki) after nephrectomy. Systolic blood pressure, which was determined by the tail-cuff method, of BN-Ki increased gradually during this treatment. In contrast, the blood pressure of mutant BN-Ka increased rapidly 2 weeks after the onset of the treatment. Urinary excretion of active kallikrein and prokallikrein increased at the same degree in rats of both strains during this treatment. Significant increase in urinary sodium excretion was observed with a tendency to increase in urine volume during the treatment in normal BN-Ki rats, whereas both parameters were essentially not increased in mutant BN-Ka rats, which could not generate urinary kinin. Aprotinin infusion by osmotic minipump to normal BN-Ki rats during the DOCA-salt treatment resulted in significant further increase in the systolic blood pressure."} {"id": "PMID:1281380", "title": "Studies on components of the plasma kallikrein system as a risk factor in diabetics undergoing cardiopulmonary bypass.", "content": "Components of the FX11-kallikrein systems were determined in blood samples from non diabetics and diabetics undergoing cardiopulmonary bypass (CPB). FX11 and prekallikrein levels fell in both groups with the largest falls in the diabetic group. Kallikrein inhibition was also lower in the diabetic group. Alpha-2-macroglobulin levels were lower in the diabetic group before operation and were markedly lower throughout CPB. Kallikrein like activities were also lower in the diabetic group. Beta FX11a inhibition values were higher in the diabetic group and fell in both groups during CPB. From the results obtained we concluded that the lower levels of FX11, prekallikrein, kallikrein inhibition and alpha-2-macroglobulin in the diabetic patients during CPB reflect enhanced activation of the FX11-plasma kallikrein systems. Blood loss in the diabetic group was higher than the for non diabetic group.", "contents": "Studies on components of the plasma kallikrein system as a risk factor in diabetics undergoing cardiopulmonary bypass. Components of the FX11-kallikrein systems were determined in blood samples from non diabetics and diabetics undergoing cardiopulmonary bypass (CPB). FX11 and prekallikrein levels fell in both groups with the largest falls in the diabetic group. Kallikrein inhibition was also lower in the diabetic group. Alpha-2-macroglobulin levels were lower in the diabetic group before operation and were markedly lower throughout CPB. Kallikrein like activities were also lower in the diabetic group. Beta FX11a inhibition values were higher in the diabetic group and fell in both groups during CPB. From the results obtained we concluded that the lower levels of FX11, prekallikrein, kallikrein inhibition and alpha-2-macroglobulin in the diabetic patients during CPB reflect enhanced activation of the FX11-plasma kallikrein systems. Blood loss in the diabetic group was higher than the for non diabetic group."} {"id": "PMID:1281381", "title": "Effects of protease inhibitors in experimental septic shock.", "content": "Endotoxin shock and contact system activation were used to study effects of hirudin, antithrombin III, eglin C, aprotinin, and [Arg15]-aprotinin in anesthetized pigs. Alterations in the systemic and pulmonary circulation were in part prevented by administration of the inhibitors.", "contents": "Effects of protease inhibitors in experimental septic shock. Endotoxin shock and contact system activation were used to study effects of hirudin, antithrombin III, eglin C, aprotinin, and [Arg15]-aprotinin in anesthetized pigs. Alterations in the systemic and pulmonary circulation were in part prevented by administration of the inhibitors."} {"id": "PMID:1281382", "title": "Eosinophilic peroxidase deficiency. Cytochemical and ultrastructural characterization of 21 new cases.", "content": "Morphologic, instrumental (flow cytometric), cytochemical, ultrastructural, and chromosomal studies were performed in 21 cases of eosinophilic peroxidase deficiency that were observed in an area of northeastern Italy in the last 5 years. It was found that eosinophilic peroxidase deficiency occurred with a frequency of 1 case in 14,000 complete blood counts yearly, and thus is less rare than previously thought. Eosinophils appeared morphologically normal when examined using the light microscope, but ultrastructural study disclosed several aspecific granule alterations. In the first family studied, members with partial and total deficit were identified; in all the other cases, the enzyme deficit was total (negative cytochemical reactions and absence of dimethylaminoazobenzene-positive specific granules at the electron microscope), isolated (a single affected member in each family examined), and stable (persistent at long-term follow-up). Eosinophilic peroxidase deficiency was not correlatable with any particular disease, although a nonsignificant association with allergic-type conditions was observed. Studies are in progress to examine the modality of the defect's genetic transmission, as well as problems related to possible functional alterations and correlated clinical consequences.", "contents": "Eosinophilic peroxidase deficiency. Cytochemical and ultrastructural characterization of 21 new cases. Morphologic, instrumental (flow cytometric), cytochemical, ultrastructural, and chromosomal studies were performed in 21 cases of eosinophilic peroxidase deficiency that were observed in an area of northeastern Italy in the last 5 years. It was found that eosinophilic peroxidase deficiency occurred with a frequency of 1 case in 14,000 complete blood counts yearly, and thus is less rare than previously thought. Eosinophils appeared morphologically normal when examined using the light microscope, but ultrastructural study disclosed several aspecific granule alterations. In the first family studied, members with partial and total deficit were identified; in all the other cases, the enzyme deficit was total (negative cytochemical reactions and absence of dimethylaminoazobenzene-positive specific granules at the electron microscope), isolated (a single affected member in each family examined), and stable (persistent at long-term follow-up). Eosinophilic peroxidase deficiency was not correlatable with any particular disease, although a nonsignificant association with allergic-type conditions was observed. Studies are in progress to examine the modality of the defect's genetic transmission, as well as problems related to possible functional alterations and correlated clinical consequences."} {"id": "PMID:1281383", "title": "The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis.", "content": "Direct flow cytometric measurement of nucleic acid content in individual platelets is possible using the fluorescent dye Thiazole Orange (Becton-Dickinson, San Jose, CA). When applied to studies of thrombocytopenic patients, platelets with elevated nucleic acid content (\"reticulated platelets\") can be identified and quantitated. Labeling of these platelets is saturable and is abolished by treatment with RNAse. It has been suggested that, similar to the erythrocyte reticulocyte response to anemia, the number of these platelets appearing in the circulation may provide an estimate of the rate of thrombopoiesis. The authors studied 229 thrombocytopenic patients, measuring both reticulated platelets and platelet-associated immunoglobulin. The results show that for the subset of patients with normal levels of platelet-associated immunoglobulin, the average absolute number of reticulated platelets is independent of platelet count and remains in the normal range. For those with elevated levels of platelet-associated immunoglobulin, the absolute number of reticulated platelets increases in patients who are moderately thrombocytopenic (60 to 100 x 10(9)/L) but decreases to normal or subnormal levels as thrombocytopenia worsens. The latter finding has been duplicated in studies of mice made thrombocytopenic by injection of anti-platelet antiserum. These results are consistent with the hypothesis that reticulated platelets are subject to peripheral destruction at the same rate as mature platelets, and that in the severely thrombocytopenic patient their level may decrease despite an appropriate marrow thrombopoietic response.", "contents": "The significance of platelets with increased RNA content (reticulated platelets). A measure of the rate of thrombopoiesis. Direct flow cytometric measurement of nucleic acid content in individual platelets is possible using the fluorescent dye Thiazole Orange (Becton-Dickinson, San Jose, CA). When applied to studies of thrombocytopenic patients, platelets with elevated nucleic acid content (\"reticulated platelets\") can be identified and quantitated. Labeling of these platelets is saturable and is abolished by treatment with RNAse. It has been suggested that, similar to the erythrocyte reticulocyte response to anemia, the number of these platelets appearing in the circulation may provide an estimate of the rate of thrombopoiesis. The authors studied 229 thrombocytopenic patients, measuring both reticulated platelets and platelet-associated immunoglobulin. The results show that for the subset of patients with normal levels of platelet-associated immunoglobulin, the average absolute number of reticulated platelets is independent of platelet count and remains in the normal range. For those with elevated levels of platelet-associated immunoglobulin, the absolute number of reticulated platelets increases in patients who are moderately thrombocytopenic (60 to 100 x 10(9)/L) but decreases to normal or subnormal levels as thrombocytopenia worsens. The latter finding has been duplicated in studies of mice made thrombocytopenic by injection of anti-platelet antiserum. These results are consistent with the hypothesis that reticulated platelets are subject to peripheral destruction at the same rate as mature platelets, and that in the severely thrombocytopenic patient their level may decrease despite an appropriate marrow thrombopoietic response."} {"id": "PMID:1281384", "title": "Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation.", "content": "The human androgen-receptor gene (HUMARA; GenBank) contains a highly polymorphic trinucleotide repeat in the first exon. We have found that the methylation of HpaII and HhaI sites less than 100 bp away from this polymorphic short tandem repeat (STR) correlates with X inactivation. The close proximity of the restriction-enzyme sites to the STR allows the development of a PCR assay that distinguishes between the maternal and paternal alleles and identifies their methylation status. The accuracy of this assay was tested on (a) DNA from hamster/human hybrid cell lines containing either an active or inactive human X chromosome; (b) DNA from normal males and females; and (c) DNA from females showing nonrandom patterns of X inactivation. Data obtained using this assay correlated substantially with those obtained using the PGK, HPRT, and M27 beta probes, which detect X inactivation patterns by Southern blot analysis. In order to demonstrate one application of this assay, we examined X inactivation patterns in the B lymphocytes of potential and obligate carriers of X-linked agammaglobulinemia.", "contents": "Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation. The human androgen-receptor gene (HUMARA; GenBank) contains a highly polymorphic trinucleotide repeat in the first exon. We have found that the methylation of HpaII and HhaI sites less than 100 bp away from this polymorphic short tandem repeat (STR) correlates with X inactivation. The close proximity of the restriction-enzyme sites to the STR allows the development of a PCR assay that distinguishes between the maternal and paternal alleles and identifies their methylation status. The accuracy of this assay was tested on (a) DNA from hamster/human hybrid cell lines containing either an active or inactive human X chromosome; (b) DNA from normal males and females; and (c) DNA from females showing nonrandom patterns of X inactivation. Data obtained using this assay correlated substantially with those obtained using the PGK, HPRT, and M27 beta probes, which detect X inactivation patterns by Southern blot analysis. In order to demonstrate one application of this assay, we examined X inactivation patterns in the B lymphocytes of potential and obligate carriers of X-linked agammaglobulinemia."} {"id": "PMID:1281385", "title": "Ethnic heterogeneity and cystic fibrosis transmembrane regulator (CFTR) mutation frequencies in Chicago-area CF families.", "content": "The identification of a common mutation, delta F508, in the CFTR gene allowed, for the first time, the detection of cystic fibrosis (CF) carriers in the general population. Further genetic studies revealed > 100 additional disease-causing mutations in this gene, few of which occur on > 1% of CF chromosomes in any ethnic group. Prior to establishing counseling guidelines and carrier risk assessments, we sought to establish the frequencies of the CFTR mutations that are present in CF families living in the Chicago area, a region notable for its ethnic heterogeneity. Our sample included 283 unrelated CF carriers, with the following ethnic composition: 78% non-Ashkenazi Caucasians, 5% Ashkenazi, 9% African-American, 3% Mexican, 0.3% Native American, and 5% mixed ancestry. When a panel of 10 mutations (delta F508, delta I507, G542X, G551D, R553X, S549N, R1162X, W1282X, N1303K, and 1717-1G-->A) was used, detection rates ranged from 75% in non-Ashkenazi Caucasians to 40% in African-Americans. These data suggest that the goal of screening for 90%-95% of CF mutations may be unrealistic in this and other, similar U.S. populations.", "contents": "Ethnic heterogeneity and cystic fibrosis transmembrane regulator (CFTR) mutation frequencies in Chicago-area CF families. The identification of a common mutation, delta F508, in the CFTR gene allowed, for the first time, the detection of cystic fibrosis (CF) carriers in the general population. Further genetic studies revealed > 100 additional disease-causing mutations in this gene, few of which occur on > 1% of CF chromosomes in any ethnic group. Prior to establishing counseling guidelines and carrier risk assessments, we sought to establish the frequencies of the CFTR mutations that are present in CF families living in the Chicago area, a region notable for its ethnic heterogeneity. Our sample included 283 unrelated CF carriers, with the following ethnic composition: 78% non-Ashkenazi Caucasians, 5% Ashkenazi, 9% African-American, 3% Mexican, 0.3% Native American, and 5% mixed ancestry. When a panel of 10 mutations (delta F508, delta I507, G542X, G551D, R553X, S549N, R1162X, W1282X, N1303K, and 1717-1G-->A) was used, detection rates ranged from 75% in non-Ashkenazi Caucasians to 40% in African-Americans. These data suggest that the goal of screening for 90%-95% of CF mutations may be unrealistic in this and other, similar U.S. populations."} {"id": "PMID:1281386", "title": "Atypical basal cell hyperplasia of the prostate.", "content": "Basal cell hyperplasia classically has been described as having bland cytologic features. During the past 2 years, we have seen 12 cases (11 in consultation) with atypical features that were confused with adenocarcinoma of the prostate. Eleven of these 12 cases contained prominent nucleoli mimicking carcinoma; in the 12th case, nuclei were enlarged, hyperchromatic, and moderately pleomorphic. Immunohistochemistry with antibodies against high-molecular-weight cytokeratin (34 beta E12) was performed in nine of the cases, verifying their basal cell nature. Additional findings in these cases were necrotic intraluminal secretions (two cases), immature squamous metaplasia (two cases), peculiar hyaline cytoplasmic globules (two cases), adenosis (one case), markedly atypical nuclei of uncertain nature occurring elsewhere in the specimen (one case), and intraluminal blue mucin (two cases). We analyzed nine cases of typical basal cell hyperplasia, all of which showed classic features of basal cell hyperplasia with benign cytology. Both atypical and classical basal cell hyperplasia were frequently infiltrated by lymphocytes such that the cytologic changes could not be attributable to inflammation. Atypical basal cell hyperplasia must be differentiated from ordinary adenocarcinoma of the prostate, prostatic intraepithelial neoplasia, and basaloid carcinoma (adenoid cystic carcinoma) of the prostate.", "contents": "Atypical basal cell hyperplasia of the prostate. Basal cell hyperplasia classically has been described as having bland cytologic features. During the past 2 years, we have seen 12 cases (11 in consultation) with atypical features that were confused with adenocarcinoma of the prostate. Eleven of these 12 cases contained prominent nucleoli mimicking carcinoma; in the 12th case, nuclei were enlarged, hyperchromatic, and moderately pleomorphic. Immunohistochemistry with antibodies against high-molecular-weight cytokeratin (34 beta E12) was performed in nine of the cases, verifying their basal cell nature. Additional findings in these cases were necrotic intraluminal secretions (two cases), immature squamous metaplasia (two cases), peculiar hyaline cytoplasmic globules (two cases), adenosis (one case), markedly atypical nuclei of uncertain nature occurring elsewhere in the specimen (one case), and intraluminal blue mucin (two cases). We analyzed nine cases of typical basal cell hyperplasia, all of which showed classic features of basal cell hyperplasia with benign cytology. Both atypical and classical basal cell hyperplasia were frequently infiltrated by lymphocytes such that the cytologic changes could not be attributable to inflammation. Atypical basal cell hyperplasia must be differentiated from ordinary adenocarcinoma of the prostate, prostatic intraepithelial neoplasia, and basaloid carcinoma (adenoid cystic carcinoma) of the prostate."} {"id": "PMID:1281387", "title": "Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas.", "content": "Thirty-five endocrine tumors of the pancreas, 17 functioning and 18 nonfunctioning, were immunohistochemically studied for the expression of proliferating cell nuclear antigen (PCNA) using 19A2 and PC10 monoclonal antibodies. The proportion of PCNA-reactive cells (PCNA index) ranged from 0.2 to 27% in functioning tumors and from 0.1% to 55% in nonfunctioning tumors. PCNA index showed a statistically significant correlation with mitotic and Ki67 indexes. The median values of PCNA index identified three groups of patients: group A (PCNA < or = 2%), including 13 functioning and six nonfunctioning tumors; group B (PCNA between 2 and 5%), including three functioning and three nonfunctioning tumors; group C (PCNA > 5%), including one functioning and nine nonfunctioning tumors. All group A tumors were confined to the pancreas. In group B, the functioning tumors were limited to the pancreas, and the nonfunctioning tumors extended to extrapancreatic tissues. All group C patients had extrapancreatic extension of the disease. At follow-up, a PCNA index higher than 5% correlated to a decreased mean survival. Our data suggest that PCNA index is a reliable tool to assess the growth fraction, discern local from advanced diseases, and predict malignancy in pancreatic endocrine tumors.", "contents": "Immunodetection of proliferating cell nuclear antigen assesses the growth fraction and predicts malignancy in endocrine tumors of the pancreas. Thirty-five endocrine tumors of the pancreas, 17 functioning and 18 nonfunctioning, were immunohistochemically studied for the expression of proliferating cell nuclear antigen (PCNA) using 19A2 and PC10 monoclonal antibodies. The proportion of PCNA-reactive cells (PCNA index) ranged from 0.2 to 27% in functioning tumors and from 0.1% to 55% in nonfunctioning tumors. PCNA index showed a statistically significant correlation with mitotic and Ki67 indexes. The median values of PCNA index identified three groups of patients: group A (PCNA < or = 2%), including 13 functioning and six nonfunctioning tumors; group B (PCNA between 2 and 5%), including three functioning and three nonfunctioning tumors; group C (PCNA > 5%), including one functioning and nine nonfunctioning tumors. All group A tumors were confined to the pancreas. In group B, the functioning tumors were limited to the pancreas, and the nonfunctioning tumors extended to extrapancreatic tissues. All group C patients had extrapancreatic extension of the disease. At follow-up, a PCNA index higher than 5% correlated to a decreased mean survival. Our data suggest that PCNA index is a reliable tool to assess the growth fraction, discern local from advanced diseases, and predict malignancy in pancreatic endocrine tumors."} {"id": "PMID:1281388", "title": "Multiclefted nuclei. A helpful feature for identification of intermediate trophoblastic cells in uterine curetting specimens.", "content": "Intermediate trophoblast is a distinct form of trophoblast, the presence of which in uterine curettings is considered a reliable indicator of intrauterine pregnancy even in the absence of chorionic villi. However, the appearance of intermediate trophoblastic cells have not been described in sufficiently specific terms to permit their reliable identification, and distinction from decidual cells can be difficult. We have noticed for some time that the intermediate trophoblastic cells often show multiple deep clefts in the nuclei, and the present study was performed to address the issue of whether this nuclear feature is reliable for their identification. We reviewed 242 uterine curettings of intrauterine pregnancy, documented by the presence of chorionic villi, and were able to find a distinct population of cells with large, hyperchromatic, multiclefted nuclei scattered in the decidua in 88% of the cases. In most instances, these cells produced a characteristic variegated pattern that was readily recognizable at low magnification. Positive immunostaining for cytokeratin (CAM 5.2) in these isolated cells within the decidua confirmed their trophoblastic nature. In contrast, multiclefted nuclei were absent in the 51 negative control cases, which included decidualized endocervical polyps (40 cases), uterine curettings from patients with tubal pregnancy (10 cases), and endometriosis with decidual change (one case). We conclude that intermediate trophoblastic cells can usually be reliably identified in curettings of intrauterine pregnancy by their characteristic nuclear multiclefting.", "contents": "Multiclefted nuclei. A helpful feature for identification of intermediate trophoblastic cells in uterine curetting specimens. Intermediate trophoblast is a distinct form of trophoblast, the presence of which in uterine curettings is considered a reliable indicator of intrauterine pregnancy even in the absence of chorionic villi. However, the appearance of intermediate trophoblastic cells have not been described in sufficiently specific terms to permit their reliable identification, and distinction from decidual cells can be difficult. We have noticed for some time that the intermediate trophoblastic cells often show multiple deep clefts in the nuclei, and the present study was performed to address the issue of whether this nuclear feature is reliable for their identification. We reviewed 242 uterine curettings of intrauterine pregnancy, documented by the presence of chorionic villi, and were able to find a distinct population of cells with large, hyperchromatic, multiclefted nuclei scattered in the decidua in 88% of the cases. In most instances, these cells produced a characteristic variegated pattern that was readily recognizable at low magnification. Positive immunostaining for cytokeratin (CAM 5.2) in these isolated cells within the decidua confirmed their trophoblastic nature. In contrast, multiclefted nuclei were absent in the 51 negative control cases, which included decidualized endocervical polyps (40 cases), uterine curettings from patients with tubal pregnancy (10 cases), and endometriosis with decidual change (one case). We conclude that intermediate trophoblastic cells can usually be reliably identified in curettings of intrauterine pregnancy by their characteristic nuclear multiclefting."} {"id": "PMID:1281390", "title": "[Screening of hepatocellular carcinoma in the middle of a high risk population in Cameroon].", "content": "We undertook a prospective study of cancerous lesions of the liver in 163 patients (136 males and 27 females) considered to be on high risk. These patients were, healthy carriers of HBs Antigen (n = 70), had chronic hepatitis (n = 45) or cirrhosis (n = 48). The screening was done from two main tests: liver ultrasound and blood alphafoetoprotein. Amongst the 163 patients, malignancy was diagnosed in 29 (22 males and 7 females) giving a prevalence of 17.8 percent: 9 cancers were diagnosed in the group with chronic hepatitis (20 percent), 20 in the group with cirrhosis (41.6 percent) and none in the group of healthy carriers. These results show that in Cameroun, cirrhosis is the most frequent abnormality associated with development of hepatocarcinoma. Thus the strategy against liver cancer should be oriented towards two main objectives; vaccination of children after eliminating healthy carriers and a regular follow-up of patients at risk.", "contents": "[Screening of hepatocellular carcinoma in the middle of a high risk population in Cameroon]. We undertook a prospective study of cancerous lesions of the liver in 163 patients (136 males and 27 females) considered to be on high risk. These patients were, healthy carriers of HBs Antigen (n = 70), had chronic hepatitis (n = 45) or cirrhosis (n = 48). The screening was done from two main tests: liver ultrasound and blood alphafoetoprotein. Amongst the 163 patients, malignancy was diagnosed in 29 (22 males and 7 females) giving a prevalence of 17.8 percent: 9 cancers were diagnosed in the group with chronic hepatitis (20 percent), 20 in the group with cirrhosis (41.6 percent) and none in the group of healthy carriers. These results show that in Cameroun, cirrhosis is the most frequent abnormality associated with development of hepatocarcinoma. Thus the strategy against liver cancer should be oriented towards two main objectives; vaccination of children after eliminating healthy carriers and a regular follow-up of patients at risk."} {"id": "PMID:1281391", "title": "A vaccine against Semliki Forest virus consisting of a monoclonal anti-idiotypic antibody cross-linked to a protein which contains virus-specific T-helper cell epitopes.", "content": "A recombinantly expressed protein, consisting of cro-beta-galactosidase at the N-terminus and amino acid residues 115 to 151 of the E2 membrane of Semliki Forest virus (SFV) at the C-terminus containing two T-helper cell epitopes of SFV, was cross-linked with glutaraldehyde to a noninternal image monoclonal anti-idiotypic antibody (ab2 alpha MAb) able to induce SFV-neutralizing anti-anti-idiotypic (ab3) antibodies in BALB/c mice. This vaccine, which might potentially induce SFV-specific T-helper cell memory, established in BALB/c mice a state of protective immunity against virulent SFV within 10 days of immunization. A steady rise in serum neutralization titre occurred from day 7 to day 28 after primary anti-idiotypic immunization, levelling off thereafter. In primarily immunized mice significant rises of serum neutralization titres, which could be indicative for an operational T-helper cell memory, were not observed after challenge on day 35 with virulent SFV. The results suggest that SFV is neutralized by ab3 antibodies shortly after challenge, preventing, thereby, virus multiplication to levels sufficient to provoke a measurable booster response.", "contents": "A vaccine against Semliki Forest virus consisting of a monoclonal anti-idiotypic antibody cross-linked to a protein which contains virus-specific T-helper cell epitopes. A recombinantly expressed protein, consisting of cro-beta-galactosidase at the N-terminus and amino acid residues 115 to 151 of the E2 membrane of Semliki Forest virus (SFV) at the C-terminus containing two T-helper cell epitopes of SFV, was cross-linked with glutaraldehyde to a noninternal image monoclonal anti-idiotypic antibody (ab2 alpha MAb) able to induce SFV-neutralizing anti-anti-idiotypic (ab3) antibodies in BALB/c mice. This vaccine, which might potentially induce SFV-specific T-helper cell memory, established in BALB/c mice a state of protective immunity against virulent SFV within 10 days of immunization. A steady rise in serum neutralization titre occurred from day 7 to day 28 after primary anti-idiotypic immunization, levelling off thereafter. In primarily immunized mice significant rises of serum neutralization titres, which could be indicative for an operational T-helper cell memory, were not observed after challenge on day 35 with virulent SFV. The results suggest that SFV is neutralized by ab3 antibodies shortly after challenge, preventing, thereby, virus multiplication to levels sufficient to provoke a measurable booster response."} {"id": "PMID:1281392", "title": "Interference with HIV-1 reverse transcriptase-catalyzed DNA chain elongation by the 5'-triphosphate of the carbocyclic analog of 2'-deoxyguanosine.", "content": "In an effort to better understand features in nucleotide analogs that result in the inhibition of HIV-1 reverse transcriptase, we have evaluated this enzyme with the 5'-triphosphate of the carbocyclic analog of 2'-deoxyguanosine (CdG-TP). CdG-TP was a reasonably potent competitive inhibitor of the incorporation of dGTP into DNA by HIV-1 reverse transcriptase using either a RNA or DNA template (Ki, 1 microM). CdG-TP was a good substrate for HIV-1 reverse transcriptase on both templates, but the DNA chain was poorly extended beyond the incorporation of CdG. These results indicate that substitution of ribose with a cyclopentane ring in nucleotides is not well tolerated by HIV-1 reverse transcriptase.", "contents": "Interference with HIV-1 reverse transcriptase-catalyzed DNA chain elongation by the 5'-triphosphate of the carbocyclic analog of 2'-deoxyguanosine. In an effort to better understand features in nucleotide analogs that result in the inhibition of HIV-1 reverse transcriptase, we have evaluated this enzyme with the 5'-triphosphate of the carbocyclic analog of 2'-deoxyguanosine (CdG-TP). CdG-TP was a reasonably potent competitive inhibitor of the incorporation of dGTP into DNA by HIV-1 reverse transcriptase using either a RNA or DNA template (Ki, 1 microM). CdG-TP was a good substrate for HIV-1 reverse transcriptase on both templates, but the DNA chain was poorly extended beyond the incorporation of CdG. These results indicate that substitution of ribose with a cyclopentane ring in nucleotides is not well tolerated by HIV-1 reverse transcriptase."} {"id": "PMID:1281393", "title": "Response of Ethiopian human immunodeficiency virus type 1 isolates to antiviral compounds.", "content": "Human immunodeficiency virus type 1 (HIV-1) isolates of 8 Ethiopian and 8 Swedish untreated AIDS-patients were examined for their sensitivity to 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI) and leukocyte-derived interferon-alpha (IFN-alpha). No significant difference in drug sensitivity was found between Ethiopian and Swedish isolates, which all were sensitive to AZT, ddI and IFN-alpha except for one Swedish isolate. This isolate exhibited a mutation at amino acid position 215. These results suggest that it should be possible to perform clinical trials in Ethiopia using the same dose regimens as in Sweden.", "contents": "Response of Ethiopian human immunodeficiency virus type 1 isolates to antiviral compounds. Human immunodeficiency virus type 1 (HIV-1) isolates of 8 Ethiopian and 8 Swedish untreated AIDS-patients were examined for their sensitivity to 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI) and leukocyte-derived interferon-alpha (IFN-alpha). No significant difference in drug sensitivity was found between Ethiopian and Swedish isolates, which all were sensitive to AZT, ddI and IFN-alpha except for one Swedish isolate. This isolate exhibited a mutation at amino acid position 215. These results suggest that it should be possible to perform clinical trials in Ethiopia using the same dose regimens as in Sweden."} {"id": "PMID:1281395", "title": "[The diagnostic process in carcinoma of the pancreas].", "content": "Early diagnosis of carcinoma of the pancreas is considerably difficult because the disease is often in the advanced stage at the time of clinical manifestation. We have, however, no choice for improving the prognosis of the disease but to make an early diagnosis by detecting small tumors. Ultrasonography (US) is the most useful diagnostic technique in detecting the initial sign of carcinoma of the pancreas. The patient suspected of having this disease should first undergo US combined with measurement of serum pancreatic enzymes (amylase or elastase-1) and the tumor marker (CA 19-9). Those patients with positive results on the first examinations should undergo dynamic CT, ERCP or endoscopic US (EUS) to corroborate suspicions of the disease. Percutaneous fine needle biopsy of the pancreas may be recommended as a reliable method for making a definite diagnosis, when these diagnostic modalities fail to elucidate the disease. In conclusion, appropriate combined use of these diagnostic techniques can facilitate the early diagnosis of carcinoma of the pancreas.", "contents": "[The diagnostic process in carcinoma of the pancreas]. Early diagnosis of carcinoma of the pancreas is considerably difficult because the disease is often in the advanced stage at the time of clinical manifestation. We have, however, no choice for improving the prognosis of the disease but to make an early diagnosis by detecting small tumors. Ultrasonography (US) is the most useful diagnostic technique in detecting the initial sign of carcinoma of the pancreas. The patient suspected of having this disease should first undergo US combined with measurement of serum pancreatic enzymes (amylase or elastase-1) and the tumor marker (CA 19-9). Those patients with positive results on the first examinations should undergo dynamic CT, ERCP or endoscopic US (EUS) to corroborate suspicions of the disease. Percutaneous fine needle biopsy of the pancreas may be recommended as a reliable method for making a definite diagnosis, when these diagnostic modalities fail to elucidate the disease. In conclusion, appropriate combined use of these diagnostic techniques can facilitate the early diagnosis of carcinoma of the pancreas."} {"id": "PMID:1281396", "title": "[Clinical and histological effects of preoperative chemotherapy for squamous cell carcinoma of the tongue].", "content": "According to the effect of preoperative chemotherapy for tongue cancer, if the operation method is modified, the modality of treatment for tongue cancer will contribute to preserve the tongue in terms of function and aesthetics as well as improve the quality of life. A clinicopathologic study on 81 patients with tongue cancer was conducted to elucidate the relationship between clinical and histological effects of preoperative chemotherapy with a single agent and multiple-drug regimens, in order to determine the safe surgical margins in the resection of squamous cell carcinoma of the tongue. Fifty patients were treated with bleomycin alone, sixteen with bleomycin and methotrexate and another fifteen with bleomycin, OK-432 and cisplatin. Multiple-drug regimens resulted in greater response rates than the single agent, but there was not always agreement in the relationship between the tumor regression rate and the histological effects of chemotherapy. The histological effects, including the residual aspects of the tumor cell population, were associated with the grade of histological malignancy according to the mode of tumor cell invasion, mitotic index of tumor cell, the tumor differentiation, the degree of stromal lymphocyte infiltration and cellular atypism. These data indicate that special consideration should be also given to the degree of histological malignancy for biopsied specimen, in addition to the tumor regression rate, in determining safe surgical margins and in the modality of treatment of tongue cancer.", "contents": "[Clinical and histological effects of preoperative chemotherapy for squamous cell carcinoma of the tongue]. According to the effect of preoperative chemotherapy for tongue cancer, if the operation method is modified, the modality of treatment for tongue cancer will contribute to preserve the tongue in terms of function and aesthetics as well as improve the quality of life. A clinicopathologic study on 81 patients with tongue cancer was conducted to elucidate the relationship between clinical and histological effects of preoperative chemotherapy with a single agent and multiple-drug regimens, in order to determine the safe surgical margins in the resection of squamous cell carcinoma of the tongue. Fifty patients were treated with bleomycin alone, sixteen with bleomycin and methotrexate and another fifteen with bleomycin, OK-432 and cisplatin. Multiple-drug regimens resulted in greater response rates than the single agent, but there was not always agreement in the relationship between the tumor regression rate and the histological effects of chemotherapy. The histological effects, including the residual aspects of the tumor cell population, were associated with the grade of histological malignancy according to the mode of tumor cell invasion, mitotic index of tumor cell, the tumor differentiation, the degree of stromal lymphocyte infiltration and cellular atypism. These data indicate that special consideration should be also given to the degree of histological malignancy for biopsied specimen, in addition to the tumor regression rate, in determining safe surgical margins and in the modality of treatment of tongue cancer."} {"id": "PMID:1281397", "title": "[Four cases of Hodgkin's disease treated with MOPP/ABV hybrid regimen using nitrogen mustard-N-oxide hydrochloride].", "content": "Four patients with fresh Hodgkin's disease were treated with MOPP/ABV hybrid regimen using nitrogen mustard-N-oxide hydrochloride (NH2-O). All patients responded well to this therapy and achieved complete remission. Toxicity was minimum except for an older patient. He was 70 years old and developed arrhythmia after MOPP therapy but recovered without any treatment. The continuation of therapy was possible by dose reduction in this case. We conclude MOPP/ABV regimen using NH2-O is valuable for the treatment of Hodgkin's disease.", "contents": "[Four cases of Hodgkin's disease treated with MOPP/ABV hybrid regimen using nitrogen mustard-N-oxide hydrochloride]. Four patients with fresh Hodgkin's disease were treated with MOPP/ABV hybrid regimen using nitrogen mustard-N-oxide hydrochloride (NH2-O). All patients responded well to this therapy and achieved complete remission. Toxicity was minimum except for an older patient. He was 70 years old and developed arrhythmia after MOPP therapy but recovered without any treatment. The continuation of therapy was possible by dose reduction in this case. We conclude MOPP/ABV regimen using NH2-O is valuable for the treatment of Hodgkin's disease."} {"id": "PMID:1281398", "title": "[Intra-arterial infusion chemotherapy for recurrent cervical lymph nodes after surgery in esophageal cancer].", "content": "We attempted intra-arterial infusion chemotherapy using a reservoir system in recurrent cervical lymph nodes after surgery for esophageal cancer, and obtained favorable results. Intra-arterial infusion chemotherapy (75 mg of cisplatin and 5 mg of peplomycin) was performed using a reservoir system connected with a catheter inserted into the left subclavian artery, because recurrent lymph nodes developed in the left supraclavicular fossa. The therapy was effective for 6 months and the quality of life was improved without side effects.", "contents": "[Intra-arterial infusion chemotherapy for recurrent cervical lymph nodes after surgery in esophageal cancer]. We attempted intra-arterial infusion chemotherapy using a reservoir system in recurrent cervical lymph nodes after surgery for esophageal cancer, and obtained favorable results. Intra-arterial infusion chemotherapy (75 mg of cisplatin and 5 mg of peplomycin) was performed using a reservoir system connected with a catheter inserted into the left subclavian artery, because recurrent lymph nodes developed in the left supraclavicular fossa. The therapy was effective for 6 months and the quality of life was improved without side effects."} {"id": "PMID:1281399", "title": "Leishmania donovani: isolation of a concanavalin-A specific antigen and its evaluation for serodiagnosis of visceral leishmaniasis.", "content": "A glycoconjugate antigen of 27-39 kDa was isolated from a cell-free extract of Leishmania donovani by affinity chromatography using a Concanavalin-A sepharose-4B column and eluted with 0.5 M alpha-methylmannoside. The antigen was recognized specifically by sera from kala-azar (visceral leishmaniasis) patients and did not react with sera from tuberculosis, leprosy or malaria patients. The antigen may therefore be useful in developing a serodiagnostic assay for visceral leishmaniasis.", "contents": "Leishmania donovani: isolation of a concanavalin-A specific antigen and its evaluation for serodiagnosis of visceral leishmaniasis. A glycoconjugate antigen of 27-39 kDa was isolated from a cell-free extract of Leishmania donovani by affinity chromatography using a Concanavalin-A sepharose-4B column and eluted with 0.5 M alpha-methylmannoside. The antigen was recognized specifically by sera from kala-azar (visceral leishmaniasis) patients and did not react with sera from tuberculosis, leprosy or malaria patients. The antigen may therefore be useful in developing a serodiagnostic assay for visceral leishmaniasis."} {"id": "PMID:1281400", "title": "Effects of a single haloperidol application to neonatal and early postnatal rats on the neurotransmitter content in the corpus striatum.", "content": "We investigated the influence of the dopamine antagonist haloperidol on the neurotransmitter content in the developing rat brain. Dopamine (DA), serotonin (5-HT) and the corresponding metabolites dopac, HVA and HIAA were determined in the corpus striatum of the rat between day 1 and day 21 pn by HPLC with electro-chemical detection. A consistent increase in the content of dopamine was found during postnatal development. The concentrations (ng/g wet tissue; mean +/- standard deviation) increased from 793 +/- 237 on day 1 pn to 4584 +/- 581 on day 21 pn, but remained still lower than in adult animals (9763 +/- 494). Similar results were found for the metabolites dopac and HVA. The content of dopac increased from 59 +/- 22 (day 1 pn) to 551 +/- 59 (day 21 pn) and the content of HVA from 53 +/- 18 (day 1 pn) to 419 +/- 41 (day 21 pn). Both metabolites were also about two times lower than in adult animals (dopac 1090 +/- 282, HVA 744 +/- 206). In contrast to dopamine and its metabolites we found no age-dependent changes in the content of 5-HT from day 1 pn (99 +/- 11) to day 14 pn (121 +/- 21). A remarkable increase in the content of 5-HT was seen from day 14 pn to day 21 pn (438 +/- 56), reaching almost adult levels (570 +/- 92). The metabolite HIAA was nearly three times higher on day 21 pn (610 +/- 123) than on day 14 pn (223 +/- 28) and two times higher than in adults (321 +/- 58).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of a single haloperidol application to neonatal and early postnatal rats on the neurotransmitter content in the corpus striatum. We investigated the influence of the dopamine antagonist haloperidol on the neurotransmitter content in the developing rat brain. Dopamine (DA), serotonin (5-HT) and the corresponding metabolites dopac, HVA and HIAA were determined in the corpus striatum of the rat between day 1 and day 21 pn by HPLC with electro-chemical detection. A consistent increase in the content of dopamine was found during postnatal development. The concentrations (ng/g wet tissue; mean +/- standard deviation) increased from 793 +/- 237 on day 1 pn to 4584 +/- 581 on day 21 pn, but remained still lower than in adult animals (9763 +/- 494). Similar results were found for the metabolites dopac and HVA. The content of dopac increased from 59 +/- 22 (day 1 pn) to 551 +/- 59 (day 21 pn) and the content of HVA from 53 +/- 18 (day 1 pn) to 419 +/- 41 (day 21 pn). Both metabolites were also about two times lower than in adult animals (dopac 1090 +/- 282, HVA 744 +/- 206). In contrast to dopamine and its metabolites we found no age-dependent changes in the content of 5-HT from day 1 pn (99 +/- 11) to day 14 pn (121 +/- 21). A remarkable increase in the content of 5-HT was seen from day 14 pn to day 21 pn (438 +/- 56), reaching almost adult levels (570 +/- 92). The metabolite HIAA was nearly three times higher on day 21 pn (610 +/- 123) than on day 14 pn (223 +/- 28) and two times higher than in adults (321 +/- 58).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281401", "title": "Mechanisms of cobalt(II) uptake into V79 Chinese hamster cells.", "content": "V79 Chinese hamster cells were used as a model for the characterization of the Co(II) uptake into mammalian cells as well as the mechanisms involved. Co(II) was taken up in a dose and time dependent manner. The uptake was exponential without saturation in the tested concentration range up to 400 microM CoCl2. Furthermore, there was a high intracellular cobalt accumulation at elevated extracellular Co(II) doses (up to 16 fold at 200 microM). The time course of Co(II) uptake showed a maximum after about 8-12 h with no further change after the longest tested incubation time (24 h). The uptake of Co(II) into V79 cells seems to be mediated by multiple mechanisms: active, energy consuming transport like ion pumps and endocytosis, since the Co(II) uptake was significantly reduced by ouabain (an inhibitor of the Na+/K+ATPase), N-ethylmaleinimide (an inhibitor of the Ca2+/Mg2+ATPase and the Na+/K+ATPase), chlorpromazine (a calmodulin antagonist and inhibitor of the Ca2+/Mg2+ ATPase) as well as by the endocytosis inhibitor chloroquine. Furthermore, the two agents iodoacetate and potassium cyanide, which produce ATP depletion, resulted in a diminution of the intracellular cobalt concentration. An uptake through anion channels could be excluded, since 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid was not inhibitory.", "contents": "Mechanisms of cobalt(II) uptake into V79 Chinese hamster cells. V79 Chinese hamster cells were used as a model for the characterization of the Co(II) uptake into mammalian cells as well as the mechanisms involved. Co(II) was taken up in a dose and time dependent manner. The uptake was exponential without saturation in the tested concentration range up to 400 microM CoCl2. Furthermore, there was a high intracellular cobalt accumulation at elevated extracellular Co(II) doses (up to 16 fold at 200 microM). The time course of Co(II) uptake showed a maximum after about 8-12 h with no further change after the longest tested incubation time (24 h). The uptake of Co(II) into V79 cells seems to be mediated by multiple mechanisms: active, energy consuming transport like ion pumps and endocytosis, since the Co(II) uptake was significantly reduced by ouabain (an inhibitor of the Na+/K+ATPase), N-ethylmaleinimide (an inhibitor of the Ca2+/Mg2+ATPase and the Na+/K+ATPase), chlorpromazine (a calmodulin antagonist and inhibitor of the Ca2+/Mg2+ ATPase) as well as by the endocytosis inhibitor chloroquine. Furthermore, the two agents iodoacetate and potassium cyanide, which produce ATP depletion, resulted in a diminution of the intracellular cobalt concentration. An uptake through anion channels could be excluded, since 4,4'-diisothiocyanostilbene-2,2'-disulphonic acid was not inhibitory."} {"id": "PMID:1281403", "title": "Risk factors for neovascular age-related macular degeneration. The Eye Disease Case-Control Study Group.", "content": "Neovascular age-related macular degeneration (AMD) is one of five retinal disorders studied in the Eye Disease Case-Control Study. Data were obtained from 421 patients with neovascular AMD and 615 controls on a broad array of possible risk factors through interviews, clinical examinations, and laboratory analyses of blood samples. Decreased risk of neovascular AMD was associated with higher levels of carotenoids in the serum samples, higher horizontal cup-to-disc ratios, and use of postmenopausal exogenous estrogens in women. Increased risk of neovascular AMD was associated with cigarette smoking, higher levels of serum cholesterol, and parity greater than zero. No support was found for sunlight exposure, serum zinc levels, or iris color as risk factors for this disease. Although no association was found with a history of cardiovascular disease itself, the associations with postmenopausal exogenous estrogen use, cigarette smoking, and serum cholesterol level are consistent with a hypothesis linking risk factors for cardiovascular disease with neovascular AMD. The association noted between serum carotenoid levels and neovascular AMD supports the hypothesis that higher levels of micronutrients with antioxidant capabilities may decrease the risk of AMD.", "contents": "Risk factors for neovascular age-related macular degeneration. The Eye Disease Case-Control Study Group. Neovascular age-related macular degeneration (AMD) is one of five retinal disorders studied in the Eye Disease Case-Control Study. Data were obtained from 421 patients with neovascular AMD and 615 controls on a broad array of possible risk factors through interviews, clinical examinations, and laboratory analyses of blood samples. Decreased risk of neovascular AMD was associated with higher levels of carotenoids in the serum samples, higher horizontal cup-to-disc ratios, and use of postmenopausal exogenous estrogens in women. Increased risk of neovascular AMD was associated with cigarette smoking, higher levels of serum cholesterol, and parity greater than zero. No support was found for sunlight exposure, serum zinc levels, or iris color as risk factors for this disease. Although no association was found with a history of cardiovascular disease itself, the associations with postmenopausal exogenous estrogen use, cigarette smoking, and serum cholesterol level are consistent with a hypothesis linking risk factors for cardiovascular disease with neovascular AMD. The association noted between serum carotenoid levels and neovascular AMD supports the hypothesis that higher levels of micronutrients with antioxidant capabilities may decrease the risk of AMD."} {"id": "PMID:1281404", "title": "Purification and characterization of a phosphatidylinositol 3-kinase complex from bovine brain by using phosphopeptide affinity columns.", "content": "Specific phosphorylated tyrosine residues in the kinase insert region of the human platelet-derived-growth-factor beta-receptor mediate the formation of multienzyme complexes with this receptor. When phosphorylated, tyrosine residue 751 within the kinase insert region mediates binding of PtdIns 3-kinase to this receptor. A 17-amino-acid peptide containing this tyrosine residue was synthesized, phosphorylated by using epidermal-growth-factor receptor and then coupled to an Actigel matrix. The tyrosine-751 phosphopeptide column is used here as a final affinity step in the purification of the PtdIns 3-kinase from bovine brain to apparent homogeneity. The active resin-bound PtdIns 3-kinase is composed of two polypeptides, p110 and p85, which are elutable with SDS-containing buffers and detectable by silver staining of polyacrylamide gels. The 85 kDa protein is shown to be identical with the recently cloned p85 alpha. Phosphotyrosine is demonstrated to be an essential part of the structure required for binding of both of these proteins and PtdIns 3-kinase activity to this peptide. The active PtdIns 3-kinase complex from bovine brain, but not recombinant p85 subunits, shows specificity for binding to phosphopeptides containing a YXXM consensus sequence. Neither PtdIns 3-kinase activity, nor the complex of p85 and 110 kDa proteins, binds to several other phosphopeptide affinity columns lacking this sequence motif. The selectivity of binding of baculovirus-expressed free p85 alpha subunit of bovine brain PtdIns 3-kinase, the closely related protein p85 beta and purified bovine brain PtdIns 3-kinase to these and other phosphopeptide columns is examined.", "contents": "Purification and characterization of a phosphatidylinositol 3-kinase complex from bovine brain by using phosphopeptide affinity columns. Specific phosphorylated tyrosine residues in the kinase insert region of the human platelet-derived-growth-factor beta-receptor mediate the formation of multienzyme complexes with this receptor. When phosphorylated, tyrosine residue 751 within the kinase insert region mediates binding of PtdIns 3-kinase to this receptor. A 17-amino-acid peptide containing this tyrosine residue was synthesized, phosphorylated by using epidermal-growth-factor receptor and then coupled to an Actigel matrix. The tyrosine-751 phosphopeptide column is used here as a final affinity step in the purification of the PtdIns 3-kinase from bovine brain to apparent homogeneity. The active resin-bound PtdIns 3-kinase is composed of two polypeptides, p110 and p85, which are elutable with SDS-containing buffers and detectable by silver staining of polyacrylamide gels. The 85 kDa protein is shown to be identical with the recently cloned p85 alpha. Phosphotyrosine is demonstrated to be an essential part of the structure required for binding of both of these proteins and PtdIns 3-kinase activity to this peptide. The active PtdIns 3-kinase complex from bovine brain, but not recombinant p85 subunits, shows specificity for binding to phosphopeptides containing a YXXM consensus sequence. Neither PtdIns 3-kinase activity, nor the complex of p85 and 110 kDa proteins, binds to several other phosphopeptide affinity columns lacking this sequence motif. The selectivity of binding of baculovirus-expressed free p85 alpha subunit of bovine brain PtdIns 3-kinase, the closely related protein p85 beta and purified bovine brain PtdIns 3-kinase to these and other phosphopeptide columns is examined."} {"id": "PMID:1281405", "title": "Zymosan-triggered tyrosine phosphorylation in mouse bone-marrow-derived macrophages is enhanced by respiratory-burst priming agents.", "content": "We have investigated the relationship between tyrosine phosphorylation and respiratory-burst activity in mouse bone-marrow-derived macrophages (BMM). We demonstrate that zymosan, an agent known to trigger the macrophage respiratory burst, also triggers the activation of tyrosine kinase activity, resulting in rapid tyrosine phosphorylation on numerous proteins, and provide evidence for the role of tyrosine phosphorylation in the triggering of the BMM respiratory burst. Agents, such as tumour necrosis factor alpha (TNF alpha), interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS), which prime the macrophage for an enhanced zymosan-triggered respiratory burst, increase tyrosine phosphorylation triggered by zymosan. The zymosan-triggered tyrosine phosphorylation and respiratory-burst activity were partially suppressed by the tyrosine kinase inhibitors alpha-cyano-3-ethoxy-4-hydroxy-5-phenylmethylcinnamide (ST638) and herbimycin A. In addition, pre-exposure of BMM to vanadate, a phosphotyrosine phosphatase inhibitor, greatly enhanced the ability of zymosan to induce tyrosine phosphorylation and trigger the respiratory burst. These data highlight the importance of the balance between tyrosine kinase and phosphotyrosine phosphatase activity in determining the ultimate level of tyrosine phosphorylation in BMM and suggest that zymosan-triggered tyrosine phosphorylation is an important biochemical signal for triggering of the respiratory burst.", "contents": "Zymosan-triggered tyrosine phosphorylation in mouse bone-marrow-derived macrophages is enhanced by respiratory-burst priming agents. We have investigated the relationship between tyrosine phosphorylation and respiratory-burst activity in mouse bone-marrow-derived macrophages (BMM). We demonstrate that zymosan, an agent known to trigger the macrophage respiratory burst, also triggers the activation of tyrosine kinase activity, resulting in rapid tyrosine phosphorylation on numerous proteins, and provide evidence for the role of tyrosine phosphorylation in the triggering of the BMM respiratory burst. Agents, such as tumour necrosis factor alpha (TNF alpha), interferon-gamma (IFN-gamma) or lipopolysaccharide (LPS), which prime the macrophage for an enhanced zymosan-triggered respiratory burst, increase tyrosine phosphorylation triggered by zymosan. The zymosan-triggered tyrosine phosphorylation and respiratory-burst activity were partially suppressed by the tyrosine kinase inhibitors alpha-cyano-3-ethoxy-4-hydroxy-5-phenylmethylcinnamide (ST638) and herbimycin A. In addition, pre-exposure of BMM to vanadate, a phosphotyrosine phosphatase inhibitor, greatly enhanced the ability of zymosan to induce tyrosine phosphorylation and trigger the respiratory burst. These data highlight the importance of the balance between tyrosine kinase and phosphotyrosine phosphatase activity in determining the ultimate level of tyrosine phosphorylation in BMM and suggest that zymosan-triggered tyrosine phosphorylation is an important biochemical signal for triggering of the respiratory burst."} {"id": "PMID:1281406", "title": "Partial purification and characterization of an endo-alpha-N-acetylgalactosaminidase from the culture medium of Streptomyces sp. OH-11242.", "content": "For the purification of a new type of endo-alpha-N-acetylgalactosaminidase from the culture medium of Streptomyces sp. OH-11242 (endo-GalNAc-ase-S) [Iwase, Ishii, Ishihara, Tanaka, Omura & Hotta (1988) Biochem. Biophys. Res. Commun. 151, 422-428], a method for assaying enzyme activity was established. Using purified pig gastric mucus glycoprotein (PGM) as the substrate, oligosaccharides liberated from PGM were pyridylaminated, and the reducing terminal sugars of oligosaccharides larger than Gal beta 1-3GalNAc were analysed by h.p.1.c. The crude enzyme of endo-GalNAc-ase-S was prepared as an 80% (w/v) ammonium sulphate precipitate from the concentrated culture medium. The enzyme was partially purified by gel chromatofocusing and subsequent DEAE-Toyopearl chromatography. Endo-enzyme activity eluted around pI 4.8 on a gel chromatofocusing column and eluted with 0.19-0.25 M-NaCl on a DEAE-Toyopearl column. In the enzyme fraction obtained, no exo-glycosidases or proteases could be detected. The molecular mass of the enzyme was estimated as 105 kDa by gel filtration, and the optimum pH was 5.5. Endo-GalNAc-ase-S hydrolysed the O-glycosidic linkage between GalNAc and Ser (Thr) in 3H-labelled and unlabelled asialofetuin, liberating both the disaccharide (Gal beta 1-3GalNAc) and the tetrasaccharide [Gal beta 1-3 (Gal beta 1-4GlcNAc beta 1-6)GalNAc]. When endo-alpha-N-acetylgalactosaminidase from Alcaligenes sp. (endo-GalNac-ase-A) was incubated with 3H-labelled and unlabelled asialofetuin, only the disaccharide (Gal beta 1-3GalNAc) was liberated.", "contents": "Partial purification and characterization of an endo-alpha-N-acetylgalactosaminidase from the culture medium of Streptomyces sp. OH-11242. For the purification of a new type of endo-alpha-N-acetylgalactosaminidase from the culture medium of Streptomyces sp. OH-11242 (endo-GalNAc-ase-S) [Iwase, Ishii, Ishihara, Tanaka, Omura & Hotta (1988) Biochem. Biophys. Res. Commun. 151, 422-428], a method for assaying enzyme activity was established. Using purified pig gastric mucus glycoprotein (PGM) as the substrate, oligosaccharides liberated from PGM were pyridylaminated, and the reducing terminal sugars of oligosaccharides larger than Gal beta 1-3GalNAc were analysed by h.p.1.c. The crude enzyme of endo-GalNAc-ase-S was prepared as an 80% (w/v) ammonium sulphate precipitate from the concentrated culture medium. The enzyme was partially purified by gel chromatofocusing and subsequent DEAE-Toyopearl chromatography. Endo-enzyme activity eluted around pI 4.8 on a gel chromatofocusing column and eluted with 0.19-0.25 M-NaCl on a DEAE-Toyopearl column. In the enzyme fraction obtained, no exo-glycosidases or proteases could be detected. The molecular mass of the enzyme was estimated as 105 kDa by gel filtration, and the optimum pH was 5.5. Endo-GalNAc-ase-S hydrolysed the O-glycosidic linkage between GalNAc and Ser (Thr) in 3H-labelled and unlabelled asialofetuin, liberating both the disaccharide (Gal beta 1-3GalNAc) and the tetrasaccharide [Gal beta 1-3 (Gal beta 1-4GlcNAc beta 1-6)GalNAc]. When endo-alpha-N-acetylgalactosaminidase from Alcaligenes sp. (endo-GalNac-ase-A) was incubated with 3H-labelled and unlabelled asialofetuin, only the disaccharide (Gal beta 1-3GalNAc) was liberated."} {"id": "PMID:1281407", "title": "Inhibition of proliferation, but not of Ca2+ mobilization, by cyclic AMP and GMP in rabbit aortic smooth-muscle cells.", "content": "The effects on cellular proliferation and Ca2+ mobilization of analogues of cyclic AMP (cAMP) and cyclic GMP (cGMP) and of agents that elevate the intracellular concentrations of cyclic nucleotides were compared in closely similar preparations of first-passage rabbit aortic vascular smooth-muscle cells. Proliferation induced by foetal-bovine serum was inhibited by 78% by 1 mM-8-bromo cAMP and by 42% by 1 mM-8-bromo cGMP. In the presence of 100 microM-isobutylmethylxanthine, 100 microM-forskolin increased intracellular cAMP concentration 5-fold and inhibited proliferation by 87%, but did not affect cGMP concentration or cell viability (ATP concentration). Similarly in the presence of 100 microM-isobutylmethylxanthine, 1 mM-SIN-1 (3-morpholinosydnonimine) elevated cGMP concentration 4-fold and inhibited proliferation by 48%, but did not affect cAMP or ATP concentration. Isobutylmethylxanthine (1 mM) elevated cAMP concentration by 3-fold and cGMP concentration by 20-fold and inhibited proliferation by 81%. Concentrations of 8-bromo cAMP, 8-bromo cGMP, forskolin or SIN-1 that inhibited proliferation did not affect the elevation of intracellular free Ca2+ concentration caused by 2% (v/v) foetal-bovine serum, 100 nM-5-hydroxytryptamine or 10 nM-angiotensin II. The results demonstrate that elevation of intracellular cAMP and cGMP concentrations both independently inhibit vascular smooth-muscle cell proliferation, but these effects on proliferation are not mediated by inhibition of Ca2+ mobilization.", "contents": "Inhibition of proliferation, but not of Ca2+ mobilization, by cyclic AMP and GMP in rabbit aortic smooth-muscle cells. The effects on cellular proliferation and Ca2+ mobilization of analogues of cyclic AMP (cAMP) and cyclic GMP (cGMP) and of agents that elevate the intracellular concentrations of cyclic nucleotides were compared in closely similar preparations of first-passage rabbit aortic vascular smooth-muscle cells. Proliferation induced by foetal-bovine serum was inhibited by 78% by 1 mM-8-bromo cAMP and by 42% by 1 mM-8-bromo cGMP. In the presence of 100 microM-isobutylmethylxanthine, 100 microM-forskolin increased intracellular cAMP concentration 5-fold and inhibited proliferation by 87%, but did not affect cGMP concentration or cell viability (ATP concentration). Similarly in the presence of 100 microM-isobutylmethylxanthine, 1 mM-SIN-1 (3-morpholinosydnonimine) elevated cGMP concentration 4-fold and inhibited proliferation by 48%, but did not affect cAMP or ATP concentration. Isobutylmethylxanthine (1 mM) elevated cAMP concentration by 3-fold and cGMP concentration by 20-fold and inhibited proliferation by 81%. Concentrations of 8-bromo cAMP, 8-bromo cGMP, forskolin or SIN-1 that inhibited proliferation did not affect the elevation of intracellular free Ca2+ concentration caused by 2% (v/v) foetal-bovine serum, 100 nM-5-hydroxytryptamine or 10 nM-angiotensin II. The results demonstrate that elevation of intracellular cAMP and cGMP concentrations both independently inhibit vascular smooth-muscle cell proliferation, but these effects on proliferation are not mediated by inhibition of Ca2+ mobilization."} {"id": "PMID:1281408", "title": "NO accounts completely for the oxygenated nitrogen species generated by enzymic L-arginine oxygenation.", "content": "We have assessed the stoichiometry of the nitric oxide (NO) synthase reaction by using a novel e.p.r. technique. NO generated by crude and partially purified NO synthase from endothelial cells and Escherichia coli-lipopolysaccharide-activated macrophages was trapped by a ferrous diethyldithiocarbamate complex dispersed in yeast. The paramagnetic ferrous mononitrosyl dithiocarbamate complex formed exhibited a characteristic e.p.r. signal at g perpendicular = 2.035 and g parallel = 2.02 with a triplet hyperfine structure (hfs) at g perpendicular. NO, 3-morpholinosydnonimine and S-nitroso-L-cysteine, but not nitrite or hydroxylamine, generated a similar e.p.r. signal. NO generated by NO synthase and by SIN-1 accumulated at a constant rate for 1 h, as measured by continuous e.p.r. registration at 37 degrees C. The formation of e.p.r.-detectable NO by NO synthases was inhibited by NG-nitro-L-arginine. Incubation with [15N]NG-L-arginine caused an e.p.r. signal with doublet hfs, indicating that the nitrosyl nitrogen derived exclusively from the guanidino nitrogen. The amount of NO generated by NO synthase as measured by e.p.r. technique was compared with formation of L-[3H]citrulline from L-[3H]arginine. NO and L-citrulline were detected at a 1:1 ratio with both NO synthase preparations. GSH and thiol depletion did not significantly affect NO synthase activity, excluding S-nitrosothiols as intermediates in the NO synthase reaction. We conclude that NO fully accounts for the immediate oxygenated nitrogen species derived from the enzymic oxygenation of L-arginine.", "contents": "NO accounts completely for the oxygenated nitrogen species generated by enzymic L-arginine oxygenation. We have assessed the stoichiometry of the nitric oxide (NO) synthase reaction by using a novel e.p.r. technique. NO generated by crude and partially purified NO synthase from endothelial cells and Escherichia coli-lipopolysaccharide-activated macrophages was trapped by a ferrous diethyldithiocarbamate complex dispersed in yeast. The paramagnetic ferrous mononitrosyl dithiocarbamate complex formed exhibited a characteristic e.p.r. signal at g perpendicular = 2.035 and g parallel = 2.02 with a triplet hyperfine structure (hfs) at g perpendicular. NO, 3-morpholinosydnonimine and S-nitroso-L-cysteine, but not nitrite or hydroxylamine, generated a similar e.p.r. signal. NO generated by NO synthase and by SIN-1 accumulated at a constant rate for 1 h, as measured by continuous e.p.r. registration at 37 degrees C. The formation of e.p.r.-detectable NO by NO synthases was inhibited by NG-nitro-L-arginine. Incubation with [15N]NG-L-arginine caused an e.p.r. signal with doublet hfs, indicating that the nitrosyl nitrogen derived exclusively from the guanidino nitrogen. The amount of NO generated by NO synthase as measured by e.p.r. technique was compared with formation of L-[3H]citrulline from L-[3H]arginine. NO and L-citrulline were detected at a 1:1 ratio with both NO synthase preparations. GSH and thiol depletion did not significantly affect NO synthase activity, excluding S-nitrosothiols as intermediates in the NO synthase reaction. We conclude that NO fully accounts for the immediate oxygenated nitrogen species derived from the enzymic oxygenation of L-arginine."} {"id": "PMID:1281409", "title": "The insulinomimetic agents H2O2 and vanadate stimulate tyrosine phosphorylation of potential target proteins for the insulin receptor kinase in intact cells.", "content": "H2O2 and vanadate are known insulinomimetic agents. Together they induce insulin's bioeffects with a potency which exceeds that seen with insulin, vanadate or H2O2 alone. We have previously shown that a combination of H2O2 and vanadate, when added to intact cells, rapidly stimulates protein tyrosine phosphorylation, owing to the inhibitory effects of these agents on intracellular protein tyrosine phosphatases (PTPases). Employing Western blotting with anti-phosphotyrosine antibodies, we have now identified in Chinese-hamster ovary (CHO) cells transfected with a wild-type insulin-receptor gene (CHO.T cells) several proteins (e.g. pp180, 125, 100, 60 and 52) whose phosphotyrosine content is rapidly increased upon treatment of the cells with a combination of insulin and 3 mM-H2O2. Tyrosine phosphorylation of these and additional proteins was further potentiated when 100 microM-sodium orthovanadate was added together with H2O2. The effects of insulin, insulin/H2O2, and H2O2/vanadate on tyrosine phosphorylation were markedly decreased in CHO cells transfected with an insulin-receptor gene where the twin tyrosines 1162 and 1163 were replaced with phenylalanine (CHO.YF-3 cells). Similarly, most of these proteins failed to undergo enhanced tyrosine phosphorylation in parental CHO cells incubated in the presence of insulin or the insulinomimetic agents. Our findings suggest that inhibition of PTPase activity by H2O2/vanadate augments the autophosphorylation of tyrosines 1162 and 1163 of the insulin receptor kinase, leading to its activation in an insulin-independent manner. As a result, tyrosine phosphorylation of potential targets for this enzyme takes place. Failure of H2O2/vanadate to induce phosphorylation of these proteins in receptor mutants lacking these twin tyrosine residues supports this hypothesis.", "contents": "The insulinomimetic agents H2O2 and vanadate stimulate tyrosine phosphorylation of potential target proteins for the insulin receptor kinase in intact cells. H2O2 and vanadate are known insulinomimetic agents. Together they induce insulin's bioeffects with a potency which exceeds that seen with insulin, vanadate or H2O2 alone. We have previously shown that a combination of H2O2 and vanadate, when added to intact cells, rapidly stimulates protein tyrosine phosphorylation, owing to the inhibitory effects of these agents on intracellular protein tyrosine phosphatases (PTPases). Employing Western blotting with anti-phosphotyrosine antibodies, we have now identified in Chinese-hamster ovary (CHO) cells transfected with a wild-type insulin-receptor gene (CHO.T cells) several proteins (e.g. pp180, 125, 100, 60 and 52) whose phosphotyrosine content is rapidly increased upon treatment of the cells with a combination of insulin and 3 mM-H2O2. Tyrosine phosphorylation of these and additional proteins was further potentiated when 100 microM-sodium orthovanadate was added together with H2O2. The effects of insulin, insulin/H2O2, and H2O2/vanadate on tyrosine phosphorylation were markedly decreased in CHO cells transfected with an insulin-receptor gene where the twin tyrosines 1162 and 1163 were replaced with phenylalanine (CHO.YF-3 cells). Similarly, most of these proteins failed to undergo enhanced tyrosine phosphorylation in parental CHO cells incubated in the presence of insulin or the insulinomimetic agents. Our findings suggest that inhibition of PTPase activity by H2O2/vanadate augments the autophosphorylation of tyrosines 1162 and 1163 of the insulin receptor kinase, leading to its activation in an insulin-independent manner. As a result, tyrosine phosphorylation of potential targets for this enzyme takes place. Failure of H2O2/vanadate to induce phosphorylation of these proteins in receptor mutants lacking these twin tyrosine residues supports this hypothesis."} {"id": "PMID:1281410", "title": "Monoclonal antibodies for dystrophin analysis. Epitope mapping and improved binding to SDS-treated muscle sections.", "content": "A group of 44 monoclonal antibodies (mAbs) raised against the central helical rod (25 mAbs) and C-terminal (19 mAbs) regions of dystrophin were prepared using trpE recombinant fusion proteins as immunogens. Some mAbs cross-react with the structurally related proteins, alpha-actinin and utrophin. Epitope mapping revealed uneven distribution of mAb-binding sites, no mAbs being produced against the C-terminal end of the helical fragment or the cysteine-rich region of the C-terminal dystrophin fragment. The failure of these large regions of the recombinant immunogens to elicit anti-dystrophin antibodies may be because of their inability to fold into the correct dystrophin-like conformation. The mAbs were selected for their ability to recognize 427 kDa dystrophin on Western blots after SDS/PAGE, and/or for immunostaining of the membrane in frozen muscle sections. Although some mAbs obtained by Western-blot screening failed to bind native dystrophin in frozen muscle sections, successful binding could be obtained after SDS or urea treatment of the tissue section to expose the epitopes. This increases the range of mAbs available for detection of dystrophin deletions in muscular dystrophy and evaluation of myoblast therapy.", "contents": "Monoclonal antibodies for dystrophin analysis. Epitope mapping and improved binding to SDS-treated muscle sections. A group of 44 monoclonal antibodies (mAbs) raised against the central helical rod (25 mAbs) and C-terminal (19 mAbs) regions of dystrophin were prepared using trpE recombinant fusion proteins as immunogens. Some mAbs cross-react with the structurally related proteins, alpha-actinin and utrophin. Epitope mapping revealed uneven distribution of mAb-binding sites, no mAbs being produced against the C-terminal end of the helical fragment or the cysteine-rich region of the C-terminal dystrophin fragment. The failure of these large regions of the recombinant immunogens to elicit anti-dystrophin antibodies may be because of their inability to fold into the correct dystrophin-like conformation. The mAbs were selected for their ability to recognize 427 kDa dystrophin on Western blots after SDS/PAGE, and/or for immunostaining of the membrane in frozen muscle sections. Although some mAbs obtained by Western-blot screening failed to bind native dystrophin in frozen muscle sections, successful binding could be obtained after SDS or urea treatment of the tissue section to expose the epitopes. This increases the range of mAbs available for detection of dystrophin deletions in muscular dystrophy and evaluation of myoblast therapy."} {"id": "PMID:1281411", "title": "[Hyperproliferation-associated keratin 16 expression in cholesteatoma].", "content": "The position of a cell in a stratified squamous epithelium correlates with its state of differentiation as well as with the expression of certain cytokeratins. By means of both immunohistochemistry using the APAAP method and high resolution one-dimensional gel electrophoresis, specimens of cholesteatoma epithelium and normal ear skin were investigated whether they contain keratin 16 (K 16) which is known to be a marker of hyperproliferation. It could be shown that K 16 is expressed in all layers of cholesteatoma epithelium. Further to prove this fact gel electrophoresis was used showing a protein band at the localization of keratin 16. Hence, cholesteatoma can be seen as a locally hyperproliferative disease.", "contents": "[Hyperproliferation-associated keratin 16 expression in cholesteatoma]. The position of a cell in a stratified squamous epithelium correlates with its state of differentiation as well as with the expression of certain cytokeratins. By means of both immunohistochemistry using the APAAP method and high resolution one-dimensional gel electrophoresis, specimens of cholesteatoma epithelium and normal ear skin were investigated whether they contain keratin 16 (K 16) which is known to be a marker of hyperproliferation. It could be shown that K 16 is expressed in all layers of cholesteatoma epithelium. Further to prove this fact gel electrophoresis was used showing a protein band at the localization of keratin 16. Hence, cholesteatoma can be seen as a locally hyperproliferative disease."} {"id": "PMID:1281412", "title": "Charcot-Marie-Tooth disease: evidence of a duplication at D17S122 locus.", "content": "The presence of 17p11.2 duplication in CMT 1 Italian families was studied. Fourteen families were tested with pVAW409R3a probe which detects the duplication at D17S122 locus. The duplication was found in all affected individuals, but not in the unaffected relatives and in the unrelated spouses. Also two sporadic cases were investigated: the duplication was present in both patients confirming this mutation as cause of the disease.", "contents": "Charcot-Marie-Tooth disease: evidence of a duplication at D17S122 locus. The presence of 17p11.2 duplication in CMT 1 Italian families was studied. Fourteen families were tested with pVAW409R3a probe which detects the duplication at D17S122 locus. The duplication was found in all affected individuals, but not in the unaffected relatives and in the unrelated spouses. Also two sporadic cases were investigated: the duplication was present in both patients confirming this mutation as cause of the disease."} {"id": "PMID:1281415", "title": "High level expression of the synthetic human lysozyme gene in Aspergillus oryzae.", "content": "Aspergillus oryzae was transformed with a synthetic gene consisting of a chicken lysozyme signal sequence and a mature human lysozyme (HLY) sequence. The transformants secreted active HLY (about 1.2 mg/l) when the HLY gene was expressed under the control of the Taka-amylase A gene (amyB) promoter. Western blot analysis suggested that the secreted protein was immunoreactive with anti-human lysozyme antibody and the signal peptide was correctly cleavaged off in the A. oryzae transformants. The transcriptional level of the HLY gene was investigated by Northern blot analysis using a probe that was equivalently specific to both the HLY gene and the amyB gene. The HLY gene was expressed at a higher level compared with the amyB gene because of its multi-copy integration. The efficient transcription of the HLY gene suggested that A. oryzae is a promising host for production of heterologous proteins from higher eukaryotes.", "contents": "High level expression of the synthetic human lysozyme gene in Aspergillus oryzae. Aspergillus oryzae was transformed with a synthetic gene consisting of a chicken lysozyme signal sequence and a mature human lysozyme (HLY) sequence. The transformants secreted active HLY (about 1.2 mg/l) when the HLY gene was expressed under the control of the Taka-amylase A gene (amyB) promoter. Western blot analysis suggested that the secreted protein was immunoreactive with anti-human lysozyme antibody and the signal peptide was correctly cleavaged off in the A. oryzae transformants. The transcriptional level of the HLY gene was investigated by Northern blot analysis using a probe that was equivalently specific to both the HLY gene and the amyB gene. The HLY gene was expressed at a higher level compared with the amyB gene because of its multi-copy integration. The efficient transcription of the HLY gene suggested that A. oryzae is a promising host for production of heterologous proteins from higher eukaryotes."} {"id": "PMID:1281416", "title": "Precocious pathfinding: retinal axons can navigate in an axonless brain.", "content": "The developing axons of retinal ganglion cells follow a stereotyped trajectory through the diencephalon to the optic tectum. In Xenopus, this trajectory closely parallels that of a preexisting fiber tract, the tract of the postoptic commissure (TPOC). This tract comprises part of the early CNS scaffold and has been proposed to play a critical role in guiding the later growing optic axons. We have tested this possibility using heterochronic and xenoplastic transplants of eye primordia to force optic axons to enter the brain before scaffold tracts have arisen in the forebrain. We show that optic axons can navigate appropriately in the absence of the TPOC or any other axons, indicating that axonal pathfinding cues are present in the axonless neuroepithelial sheet. We suggest that molecularly distinct heterogeneities within the neuroepithelium are used for pathfinding by early and late developing axons alike in normal development.", "contents": "Precocious pathfinding: retinal axons can navigate in an axonless brain. The developing axons of retinal ganglion cells follow a stereotyped trajectory through the diencephalon to the optic tectum. In Xenopus, this trajectory closely parallels that of a preexisting fiber tract, the tract of the postoptic commissure (TPOC). This tract comprises part of the early CNS scaffold and has been proposed to play a critical role in guiding the later growing optic axons. We have tested this possibility using heterochronic and xenoplastic transplants of eye primordia to force optic axons to enter the brain before scaffold tracts have arisen in the forebrain. We show that optic axons can navigate appropriately in the absence of the TPOC or any other axons, indicating that axonal pathfinding cues are present in the axonless neuroepithelial sheet. We suggest that molecularly distinct heterogeneities within the neuroepithelium are used for pathfinding by early and late developing axons alike in normal development."} {"id": "PMID:1281417", "title": "Nerve growth factor mediates signal transduction through trk homodimer receptors.", "content": "We have investigated the molecular nature of the high affinity nerve growth factor (NGF) receptors by using cell lines expressing gp75LNGFR and gp140trk. Our results suggest that gp75LNGFR and gp140trk interact with NGF independently and that only gp140trk mediates NGF signaling. NGF binds to gp140trk with picomolar affinity and induces its phosphorylation on tyrosine residues regardless of the presence of gp75LNGFR. NGF-gp140trk complexes display the slow dissociation rate and rapid internalization characteristics of high affinity NGF receptors. Cross-linking studies reveal the existence of gp75LNGFR and gp140trk homodimers. However, we were unable to detect gp75LNGFR-gp140trk heterodimers. Coexpression in COS cells of wild-type and kinase deficient mutants reveals that gp140trk receptors can undergo intermolecular phosphorylation, indicating the formation of functional homodimers. Moreover, these kinase deficient mutants inhibit NGF-induced signaling through wild-type gp140trk receptors. These results indicate that the functional high affinity NGF receptors consist of gp140trk homodimeric (or oligomeric) complexes.", "contents": "Nerve growth factor mediates signal transduction through trk homodimer receptors. We have investigated the molecular nature of the high affinity nerve growth factor (NGF) receptors by using cell lines expressing gp75LNGFR and gp140trk. Our results suggest that gp75LNGFR and gp140trk interact with NGF independently and that only gp140trk mediates NGF signaling. NGF binds to gp140trk with picomolar affinity and induces its phosphorylation on tyrosine residues regardless of the presence of gp75LNGFR. NGF-gp140trk complexes display the slow dissociation rate and rapid internalization characteristics of high affinity NGF receptors. Cross-linking studies reveal the existence of gp75LNGFR and gp140trk homodimers. However, we were unable to detect gp75LNGFR-gp140trk heterodimers. Coexpression in COS cells of wild-type and kinase deficient mutants reveals that gp140trk receptors can undergo intermolecular phosphorylation, indicating the formation of functional homodimers. Moreover, these kinase deficient mutants inhibit NGF-induced signaling through wild-type gp140trk receptors. These results indicate that the functional high affinity NGF receptors consist of gp140trk homodimeric (or oligomeric) complexes."} {"id": "PMID:1281418", "title": "Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels.", "content": "Functional maturation of the nicotinic acetylcholine receptor is executed by its gamma-to-epsilon subunit switching. The glycine receptor also has fetal (alpha 2) and adult (alpha 1) isoforms. However, whether subunit switching is responsible for developmental changes in glycine receptor function is not known. We recorded single-channel currents from homomeric glycine receptors expressed in Xenopus oocytes with cRNAs encoding the alpha 2 or alpha 1 subunits and compared them with those recorded from native glycine receptors in rat spinal neurons at various ontogenic periods. The mean channel life times of the alpha 1 and mature glycine receptors were equally short, whereas both the alpha 2 and fetal receptors showed a significantly longer open time. Consistent with these results, the decay time of the glycinergic inhibitory postsynaptic currents (IPSCs) in spinal neurons became shorter during postnatal development. We conclude that developmental switching of alpha subunits may accelerate the kinetics of IPSCs.", "contents": "Functional correlation of fetal and adult forms of glycine receptors with developmental changes in inhibitory synaptic receptor channels. Functional maturation of the nicotinic acetylcholine receptor is executed by its gamma-to-epsilon subunit switching. The glycine receptor also has fetal (alpha 2) and adult (alpha 1) isoforms. However, whether subunit switching is responsible for developmental changes in glycine receptor function is not known. We recorded single-channel currents from homomeric glycine receptors expressed in Xenopus oocytes with cRNAs encoding the alpha 2 or alpha 1 subunits and compared them with those recorded from native glycine receptors in rat spinal neurons at various ontogenic periods. The mean channel life times of the alpha 1 and mature glycine receptors were equally short, whereas both the alpha 2 and fetal receptors showed a significantly longer open time. Consistent with these results, the decay time of the glycinergic inhibitory postsynaptic currents (IPSCs) in spinal neurons became shorter during postnatal development. We conclude that developmental switching of alpha subunits may accelerate the kinetics of IPSCs."} {"id": "PMID:1281419", "title": "P-type calcium channels in the somata and dendrites of adult cerebellar Purkinje cells.", "content": "The pharmacological and single-channel properties of Ca2+ channels were studied in the somata and dendrites of adult cerebellar Purkinje cells. The Ca2+ channels were exclusively of the high threshold type: low threshold Ca2+ channels were not found. These high threshold channels were not blocked by omega-conotoxin GVIA and were inhibited rather than activated by BAY K 8644. They were therefore pharmacologically distinct from high threshold N- and L-type channels. Funnel web spider toxin was an effective blocker. The channels opened to conductance levels of 9, 14, and 19 pS (in 110 mM Ba2+). These slope conductances were in the range of those reported for N- and L-type channels. Our results are in agreement with previous reports suggesting that Ca2+ channels in Purkinje cells can be classified as P-type channels according to their pharmacology. The results also suggest that distinctions among Ca2+ channel types based on the single-channel conductance are not definitive.", "contents": "P-type calcium channels in the somata and dendrites of adult cerebellar Purkinje cells. The pharmacological and single-channel properties of Ca2+ channels were studied in the somata and dendrites of adult cerebellar Purkinje cells. The Ca2+ channels were exclusively of the high threshold type: low threshold Ca2+ channels were not found. These high threshold channels were not blocked by omega-conotoxin GVIA and were inhibited rather than activated by BAY K 8644. They were therefore pharmacologically distinct from high threshold N- and L-type channels. Funnel web spider toxin was an effective blocker. The channels opened to conductance levels of 9, 14, and 19 pS (in 110 mM Ba2+). These slope conductances were in the range of those reported for N- and L-type channels. Our results are in agreement with previous reports suggesting that Ca2+ channels in Purkinje cells can be classified as P-type channels according to their pharmacology. The results also suggest that distinctions among Ca2+ channel types based on the single-channel conductance are not definitive."} {"id": "PMID:1281420", "title": "L-myc and N-myc influence lineage determination in the central nervous system.", "content": "The N-myc and the L-myc proto-oncogenes are expressed during embryonal development mainly in the developing brain. Studies of their expression in single neuroepithelial cells revealed that neural precursors not yet committed to the glial or the neuronal lineage expressed both genes, but after lineage commitment they expressed either N-myc or L-myc. Moreover, enforced expression of L-myc in the neural precursor cell line 2.3D caused neuronal differentiation, while the expression of N-myc promoted glial differentiation. These results indicate that L-myc and N-myc play critical roles in lineage determination for the central nervous system.", "contents": "L-myc and N-myc influence lineage determination in the central nervous system. The N-myc and the L-myc proto-oncogenes are expressed during embryonal development mainly in the developing brain. Studies of their expression in single neuroepithelial cells revealed that neural precursors not yet committed to the glial or the neuronal lineage expressed both genes, but after lineage commitment they expressed either N-myc or L-myc. Moreover, enforced expression of L-myc in the neural precursor cell line 2.3D caused neuronal differentiation, while the expression of N-myc promoted glial differentiation. These results indicate that L-myc and N-myc play critical roles in lineage determination for the central nervous system."} {"id": "PMID:1281421", "title": "Intracranial germ cell tumours: I. Experience with platinum based chemotherapy and implications for curative chemoradiotherapy.", "content": "The results of treatment with platinum based combination chemotherapy in ten patients with intracranial germ cell tumours (GCT) are presented. Two patients, treated for relapse within the central nervous system (CNS), attained partial responses of short duration. One patient with systemic relapse was successfully salvaged with chemotherapy. Seven patients received primary chemotherapy, six of whom received a 'CNS friendly' regimen consisting of vincristine, etoposide, carboplatin (VEJ) prior to craniospinal axis (CSA) irradiation. Three complete and three partial responses, and one patient with stable disease, were seen prior to irradiation. All seven patients are alive and remain disease-free at a median time of 12 months after treatment. Current treatment policy for germinomas attaining complete response to two courses of VEJ is a lowered CSA dose prescription, while non-germinomatous germ cell tumours (NGGCT) receive standard total dose CSA irradiation.", "contents": "Intracranial germ cell tumours: I. Experience with platinum based chemotherapy and implications for curative chemoradiotherapy. The results of treatment with platinum based combination chemotherapy in ten patients with intracranial germ cell tumours (GCT) are presented. Two patients, treated for relapse within the central nervous system (CNS), attained partial responses of short duration. One patient with systemic relapse was successfully salvaged with chemotherapy. Seven patients received primary chemotherapy, six of whom received a 'CNS friendly' regimen consisting of vincristine, etoposide, carboplatin (VEJ) prior to craniospinal axis (CSA) irradiation. Three complete and three partial responses, and one patient with stable disease, were seen prior to irradiation. All seven patients are alive and remain disease-free at a median time of 12 months after treatment. Current treatment policy for germinomas attaining complete response to two courses of VEJ is a lowered CSA dose prescription, while non-germinomatous germ cell tumours (NGGCT) receive standard total dose CSA irradiation."} {"id": "PMID:1281422", "title": "An audit of survival in small cell lung cancer.", "content": "A total of 351 previously untreated patients presented to this department with limited small cell bronchogenic carcinoma between 1974 and 1985. They were treated with either radical or palliative radiotherapy (152), chemotherapy alone (63), or combined chemoradiotherapy (136). Their 5-year survival rates were 2.6%, 0%, and 5.1% with median survival being 25.7, 29.0 and 47.4 weeks, respectively. Forty-seven patients were given radical radiotherapy, 30 of these received chemotherapy as initial treatment (20), as adjuvant (3) or at relapse (7). Their 5-year survival rate was 12.8%, with a median of 58 weeks, compared with 2.1% and 31.5 weeks for 241 patients who had palliative radiotherapy (P < 0.001). Seventeen of the 47 patients (36%) and 135 of the 241 patients (56%) were given radiotherapy alone. Univariate analysis showed that gender and age had no significant influence on survival but lymph node status did. The median survival for patients who had no lymph node metastases was 37 weeks compared with 24.5 for those who had (P < 0.01). The median and long-term survival rates for patients in this report contradict previous reports that radiotherapy has no influence on survival. Only patients who received radiotherapy, either alone, or with chemotherapy, have survived 5 years.", "contents": "An audit of survival in small cell lung cancer. A total of 351 previously untreated patients presented to this department with limited small cell bronchogenic carcinoma between 1974 and 1985. They were treated with either radical or palliative radiotherapy (152), chemotherapy alone (63), or combined chemoradiotherapy (136). Their 5-year survival rates were 2.6%, 0%, and 5.1% with median survival being 25.7, 29.0 and 47.4 weeks, respectively. Forty-seven patients were given radical radiotherapy, 30 of these received chemotherapy as initial treatment (20), as adjuvant (3) or at relapse (7). Their 5-year survival rate was 12.8%, with a median of 58 weeks, compared with 2.1% and 31.5 weeks for 241 patients who had palliative radiotherapy (P < 0.001). Seventeen of the 47 patients (36%) and 135 of the 241 patients (56%) were given radiotherapy alone. Univariate analysis showed that gender and age had no significant influence on survival but lymph node status did. The median survival for patients who had no lymph node metastases was 37 weeks compared with 24.5 for those who had (P < 0.01). The median and long-term survival rates for patients in this report contradict previous reports that radiotherapy has no influence on survival. Only patients who received radiotherapy, either alone, or with chemotherapy, have survived 5 years."} {"id": "PMID:1281423", "title": "Proteolipid protein (PLP) of CNS myelin: positions of free, disulfide-bonded, and fatty acid thioester-linked cysteine residues and implications for the membrane topology of PLP.", "content": "Proteolipid protein (PLP), the major integral membrane protein of central nervous system myelin, contains 14 cysteine residues within its 276-residue polypeptide chain. We determined the state of all cysteine residues and localized four of them as free thiols at positions 24, 32, 34, and 168. Four cysteines are connected by disulfide bonds: Cys200-Cys219 and Cys183-Cys227. The remaining six cysteine residues at positions 5, 6, 9, 108, 138, and 140 are modified by long-chain fatty acids, mainly palmitic acid, in thioester linkage. The extreme hydrophobicity of PLP can therefore be explained by two structural features: a composition of approximately 50% apolar amino acid residues and a high degree of fatty acid acylation. A differential fluorescent-labeling technique was developed for the structural studies: the cysteine residues belonging to one of the three states were derivatized by N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid (I-AEDANS) either directly (a), after thioester cleavage with hydroxylamine (b), or after disulfide cleavage with dithiothreitol (c). The protein was then proteolytically digested with thermolysin, and the labeled peptides were isolated by reversed-phase HPLC followed by sequence analysis. The results were further confirmed by determination of the fatty acid to protein stoichiometry. The structural data not only demand the revision of our concept of the membrane topology of PLP but will also promote more sophisticated studies on the mechanism of myelination and new functions of PLP.", "contents": "Proteolipid protein (PLP) of CNS myelin: positions of free, disulfide-bonded, and fatty acid thioester-linked cysteine residues and implications for the membrane topology of PLP. Proteolipid protein (PLP), the major integral membrane protein of central nervous system myelin, contains 14 cysteine residues within its 276-residue polypeptide chain. We determined the state of all cysteine residues and localized four of them as free thiols at positions 24, 32, 34, and 168. Four cysteines are connected by disulfide bonds: Cys200-Cys219 and Cys183-Cys227. The remaining six cysteine residues at positions 5, 6, 9, 108, 138, and 140 are modified by long-chain fatty acids, mainly palmitic acid, in thioester linkage. The extreme hydrophobicity of PLP can therefore be explained by two structural features: a composition of approximately 50% apolar amino acid residues and a high degree of fatty acid acylation. A differential fluorescent-labeling technique was developed for the structural studies: the cysteine residues belonging to one of the three states were derivatized by N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonic acid (I-AEDANS) either directly (a), after thioester cleavage with hydroxylamine (b), or after disulfide cleavage with dithiothreitol (c). The protein was then proteolytically digested with thermolysin, and the labeled peptides were isolated by reversed-phase HPLC followed by sequence analysis. The results were further confirmed by determination of the fatty acid to protein stoichiometry. The structural data not only demand the revision of our concept of the membrane topology of PLP but will also promote more sophisticated studies on the mechanism of myelination and new functions of PLP."} {"id": "PMID:1281424", "title": "Nonlocal interactions stabilize compact folding intermediates in reduced unfolded bovine pancreatic trypsin inhibitor.", "content": "To further our understanding of the protein folding process, it is desirable to examine the structural intermediates (equilibrium and kinetic) that are populated between the statistical coil state and the folded molecule. X-ray crystallography and NMR structural studies are unable to determine long-range distances in proteins under denaturing solution conditions. Nonradiative (F\u00f6rster) energy transfer, however, has been shown to be a spectroscopic ruler for the measurement of distance distributions and diffusion between selected sites in proteins under a range of different solution conditions. The distributions of distances between a donor probe at the N-terminal residue and an acceptor attached to one of the four lysine residues (15, 26, 41, 46) of reduced and unfolded (in 6 M guanidine hydrochloride and 20 mM dithiothreitol) bovine pancreatic trypsin inhibitor (BPTI) were measured as a function of temperature. Even in strong denaturant and reducing agent, BPTI does not exist as a statistical coil polypeptide. It appears that nonlocal (long-range) interactions are already beginning to \"fold\" the protein toward a more compact, native conformation. As the temperature is increased under these conditions, hydrophobic interactions lead to an even more compact structure consistent with the predictions of phase diagrams for globular proteins.", "contents": "Nonlocal interactions stabilize compact folding intermediates in reduced unfolded bovine pancreatic trypsin inhibitor. To further our understanding of the protein folding process, it is desirable to examine the structural intermediates (equilibrium and kinetic) that are populated between the statistical coil state and the folded molecule. X-ray crystallography and NMR structural studies are unable to determine long-range distances in proteins under denaturing solution conditions. Nonradiative (F\u00f6rster) energy transfer, however, has been shown to be a spectroscopic ruler for the measurement of distance distributions and diffusion between selected sites in proteins under a range of different solution conditions. The distributions of distances between a donor probe at the N-terminal residue and an acceptor attached to one of the four lysine residues (15, 26, 41, 46) of reduced and unfolded (in 6 M guanidine hydrochloride and 20 mM dithiothreitol) bovine pancreatic trypsin inhibitor (BPTI) were measured as a function of temperature. Even in strong denaturant and reducing agent, BPTI does not exist as a statistical coil polypeptide. It appears that nonlocal (long-range) interactions are already beginning to \"fold\" the protein toward a more compact, native conformation. As the temperature is increased under these conditions, hydrophobic interactions lead to an even more compact structure consistent with the predictions of phase diagrams for globular proteins."} {"id": "PMID:1281425", "title": "Effects of the level of mRNA expression on biophysical properties, sensitivity to neurotoxins, and regulation of the brain delayed-rectifier K+ channels Kv1.2.", "content": "Injection of 0.2 ng of cRNA encoding the brain Kv1.2 channel into Xenopus oocytes leads to the expression of a very slowly inactivating K+ current. Inactivation is absent in oocytes injected with 20 ng of cRNA although activation remains unchanged. Low cRNA concentrations generate a channel which is sensitive to dendrotoxin I (IC50 = 2 nM at 0.2 ng of cRNA/oocyte) and to less potent analogs of this toxin from Dendroaspis polylepis venom. A good correlation is found between blockade of the K+ current and binding of the different toxins to rat brain membranes. High cRNA concentrations generate another form of the K+ channel which is largely insensitive to dendrotoxin I (IC50 = 200 nM at 20 ng of cRNA per oocyte). At low cRNA concentrations, the expressed Kv1.2 channel is also blocked by other polypeptide toxins such as MCD peptide (IC50 = 20 nM), charybdotoxin (IC50 = 50 nM), and beta-bungarotoxin (IC50 = 50 nM), which bind to distinct and allosterically related sites on the channel protein. The pharmacologically distinct type of K+ channel expressed at high cRNA concentrations (20 ng of cRNA/oocyte) is nearly totally resistant to 100 nM MCD peptide and hardly altered by charybdotoxin and beta-bungarotoxin at concentrations as high as 1 microM. Both at low and at high cRNA concentrations, the expressed Kv1.2 channel is blocked by an increase in intracellular Ca2+ from the inositol trisphosphate sensitive pools and by the phorbol ester PMA that activates protein kinase C.", "contents": "Effects of the level of mRNA expression on biophysical properties, sensitivity to neurotoxins, and regulation of the brain delayed-rectifier K+ channels Kv1.2. Injection of 0.2 ng of cRNA encoding the brain Kv1.2 channel into Xenopus oocytes leads to the expression of a very slowly inactivating K+ current. Inactivation is absent in oocytes injected with 20 ng of cRNA although activation remains unchanged. Low cRNA concentrations generate a channel which is sensitive to dendrotoxin I (IC50 = 2 nM at 0.2 ng of cRNA/oocyte) and to less potent analogs of this toxin from Dendroaspis polylepis venom. A good correlation is found between blockade of the K+ current and binding of the different toxins to rat brain membranes. High cRNA concentrations generate another form of the K+ channel which is largely insensitive to dendrotoxin I (IC50 = 200 nM at 20 ng of cRNA per oocyte). At low cRNA concentrations, the expressed Kv1.2 channel is also blocked by other polypeptide toxins such as MCD peptide (IC50 = 20 nM), charybdotoxin (IC50 = 50 nM), and beta-bungarotoxin (IC50 = 50 nM), which bind to distinct and allosterically related sites on the channel protein. The pharmacologically distinct type of K+ channel expressed at high cRNA concentrations (20 ng of cRNA/oocyte) is nearly totally resistant to 100 nM MCD peptide and hardly altered by charybdotoxin and beta-bungarotoxin at concentrations as high as 1 microM. Both at low and at high cRNA concentrations, the expressed Kv1.2 channel is blocked by an increase in intracellular Ca2+ from the inositol trisphosphate sensitive pools and by the phorbol ester PMA that activates protein kinase C."} {"id": "PMID:1281426", "title": "Identification of functional arginines in human angiogenin by site-directed mutagenesis.", "content": "Chemical modifications of human angiogenin had suggested that arginines are essential for its ribonucleolytic activity [Shapiro, R., Weremowicz, S., Riordan, J. F., & Vallee, B. L. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8783-8787]. Each of the six arginines within or near angiogenin's catalytic or cell-binding sites--i.e., those at positions 5, 31, 32, 33, 66, and 70--was therefore mutated to alanine. Two of these residues, Arg-5 and Arg-33, indeed play a role, albeit noncrucial, in enzymatic activity, although neither one is implicated in the abolition of activity by arginine reagents. R5A-angiogenin, while nearly fully active toward dinucleotides, is one-fourth as active as angiogenin toward tRNA, suggesting that Arg-5 may participate in the binding of peripheral components of the substrate. In contrast, the activity of R33A-angiogenin toward both polynucleotide and dinucleotide substrates is reduced similarly, reflecting a decrease in kcat. These results, together with its position in the calculated three-dimensional structure of angiogenin, imply an indirect role for Arg-33 in catalysis. Three arginines are important for angiogenesis: mutation of Arg-5, Arg-33, or Arg-66 dramatically reduces the angiogenic potency of angiogenin on the chicken embryo chorioallantoic membrane. Arg-66 lies within a segment previously proposed to be part of a cell-surface receptor binding site. Arg-5 and Arg-33 are outside of this site as defined at present, and the decreased angiogenicity of R5A- and R33A-angiogenin may be a consequence of their reduced ribonucleolytic activities.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Identification of functional arginines in human angiogenin by site-directed mutagenesis. Chemical modifications of human angiogenin had suggested that arginines are essential for its ribonucleolytic activity [Shapiro, R., Weremowicz, S., Riordan, J. F., & Vallee, B. L. (1987) Proc. Natl. Acad. Sci. U.S.A. 84, 8783-8787]. Each of the six arginines within or near angiogenin's catalytic or cell-binding sites--i.e., those at positions 5, 31, 32, 33, 66, and 70--was therefore mutated to alanine. Two of these residues, Arg-5 and Arg-33, indeed play a role, albeit noncrucial, in enzymatic activity, although neither one is implicated in the abolition of activity by arginine reagents. R5A-angiogenin, while nearly fully active toward dinucleotides, is one-fourth as active as angiogenin toward tRNA, suggesting that Arg-5 may participate in the binding of peripheral components of the substrate. In contrast, the activity of R33A-angiogenin toward both polynucleotide and dinucleotide substrates is reduced similarly, reflecting a decrease in kcat. These results, together with its position in the calculated three-dimensional structure of angiogenin, imply an indirect role for Arg-33 in catalysis. Three arginines are important for angiogenesis: mutation of Arg-5, Arg-33, or Arg-66 dramatically reduces the angiogenic potency of angiogenin on the chicken embryo chorioallantoic membrane. Arg-66 lies within a segment previously proposed to be part of a cell-surface receptor binding site. Arg-5 and Arg-33 are outside of this site as defined at present, and the decreased angiogenicity of R5A- and R33A-angiogenin may be a consequence of their reduced ribonucleolytic activities.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281427", "title": "Structural analysis of lipooligosaccharide produced by Neisseria gonorrhoeae, strain MS11mk (variant A): a precursor for a gonococcal lipooligosaccharide associated with virulence.", "content": "We studied the structure of the lipooligosaccharide (LOS) that is produced by a variant A of strain MS11mk. This variant produces a single LOS that is recognized by monoclonal antibody (MAb) 2-1-L8. In a recent study of the pathogenesis of Neisseria gonorrhoeae in male volunteers, variant A gave rise to other phase variants that produce higher molecular weight LOSs, and these LOS were associated with virulence. Definition of the structure of the variant A LOS is important to understand the biosynthesis of LOS and its expression in vivo. The dephosphorylated oligosaccharide (OS) structure derived from the variant A LOS was analyzed by two-dimensional NMR and methylation analysis. The OS structure was found to be a truncated form of the LOS produced by strain F62 [Yamasaki et al. (1991) Biochemistry 30, 10566-10575]; the variant A OS is a hexamer, a beta-lactosyl residue linked to a tetrasaccharide: Gal beta 1-->4Glc beta 1-->4[GlcNAc alpha 1-->2Hep alpha 1-->3]Hep alpha 1-->KDO. We determined that the variant A LOS is a precursor for the synthesis of higher MW LOS. We also studied expression of the MAb 2-1-L8-defined epitope present on the variant A LOS. Our data indicate that the MAb-defined epitope is not a linear beta-lactosyl residue but its specificity is directed toward the phosphorylated GlcNAc-Hep-Hep residue. Since this MAb binds to gonococci, at least part of the phosphorylated diheptose area is exposed on the gonococcal surface.", "contents": "Structural analysis of lipooligosaccharide produced by Neisseria gonorrhoeae, strain MS11mk (variant A): a precursor for a gonococcal lipooligosaccharide associated with virulence. We studied the structure of the lipooligosaccharide (LOS) that is produced by a variant A of strain MS11mk. This variant produces a single LOS that is recognized by monoclonal antibody (MAb) 2-1-L8. In a recent study of the pathogenesis of Neisseria gonorrhoeae in male volunteers, variant A gave rise to other phase variants that produce higher molecular weight LOSs, and these LOS were associated with virulence. Definition of the structure of the variant A LOS is important to understand the biosynthesis of LOS and its expression in vivo. The dephosphorylated oligosaccharide (OS) structure derived from the variant A LOS was analyzed by two-dimensional NMR and methylation analysis. The OS structure was found to be a truncated form of the LOS produced by strain F62 [Yamasaki et al. (1991) Biochemistry 30, 10566-10575]; the variant A OS is a hexamer, a beta-lactosyl residue linked to a tetrasaccharide: Gal beta 1-->4Glc beta 1-->4[GlcNAc alpha 1-->2Hep alpha 1-->3]Hep alpha 1-->KDO. We determined that the variant A LOS is a precursor for the synthesis of higher MW LOS. We also studied expression of the MAb 2-1-L8-defined epitope present on the variant A LOS. Our data indicate that the MAb-defined epitope is not a linear beta-lactosyl residue but its specificity is directed toward the phosphorylated GlcNAc-Hep-Hep residue. Since this MAb binds to gonococci, at least part of the phosphorylated diheptose area is exposed on the gonococcal surface."} {"id": "PMID:1281428", "title": "Cofactor triggers the conformational change in thymidylate synthase: implications for an ordered binding mechanism.", "content": "We have solved crystal structures of two complexes with Escherichia coli thymidylate synthase (TS) bound either to the cofactor analog N10-propargyl-5,8-dideazafolate (CB3717) or to a tighter binding polygutamyl derivative of CB3717. These structures suggest that cofactor binding alone is sufficient to induce the conformational change in TS; dUMP binding is not required. Because polyglutamyl folates are the primary cofactor form in vivo, and because they can bind more tightly than dUMP to TS, these structures may represent a key intermediate along the TS reaction pathway. These structures further suggest that the dUMP binding site is accessible in the TS-cofactor analog binary complexes. Conformational flexibility of the binary complex may permit dUMP to enter the active site of TS while the cofactor is bound. Alternatively, dUMP may enter the active site from the opposite side that the cofactor appears to enter; that is, through a portal flanked by arginines that also coordinate the phosphate group in the active site. Entry of dUMP through this portal may allow dUMP to bind to a TS-cofactor binary complex in which the complex has completed its conformational transition to the catalytically competent structure.", "contents": "Cofactor triggers the conformational change in thymidylate synthase: implications for an ordered binding mechanism. We have solved crystal structures of two complexes with Escherichia coli thymidylate synthase (TS) bound either to the cofactor analog N10-propargyl-5,8-dideazafolate (CB3717) or to a tighter binding polygutamyl derivative of CB3717. These structures suggest that cofactor binding alone is sufficient to induce the conformational change in TS; dUMP binding is not required. Because polyglutamyl folates are the primary cofactor form in vivo, and because they can bind more tightly than dUMP to TS, these structures may represent a key intermediate along the TS reaction pathway. These structures further suggest that the dUMP binding site is accessible in the TS-cofactor analog binary complexes. Conformational flexibility of the binary complex may permit dUMP to enter the active site of TS while the cofactor is bound. Alternatively, dUMP may enter the active site from the opposite side that the cofactor appears to enter; that is, through a portal flanked by arginines that also coordinate the phosphate group in the active site. Entry of dUMP through this portal may allow dUMP to bind to a TS-cofactor binary complex in which the complex has completed its conformational transition to the catalytically competent structure."} {"id": "PMID:1281429", "title": "Dissociation between release and gene expression of gonadotropin alpha-subunit in gonadotropin-releasing hormone-stimulated alpha T3-1 cell line.", "content": "The alpha T3-1 cell line which was derived by targeted tumorigenesis in transgenic mice [Windle et al. (1990) Mol. Endocrinol. 4, 597-603] possesses high-affinity binding sites for GnRH analogs coupled to enhanced phosphoinositide turnover and phospholipase D activity. Incubation of alpha T3-1 cells with [D-Trp6]-GnRH analog (GnRH-A) resulted in a rapid increase in gonadotropin alpha-subunit mRNA levels which was detected already at 30 min of incubation (0.1 nM GnRH-A, 3-fold, p < 0.01). The effect diminished with time to reach basal levels at about 12 h of incubation, with a secondary rise in alpha mRNA levels between 12 and 24 h of incubation. Addition of the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 ng/mL) or the Ca2+ ionophore ionomycin (1 microM) to alpha T3-1 cells also resulted in a rapid increase in alpha-subunit mRNA levels. Surprisingly, GnRH-induced alpha-subunit release was detected only after a lag of 4 h of incubation. Thus, dissociation between exocytosis and gene expression can be demonstrated in GnRH-stimulated alpha T3-1 cell line.", "contents": "Dissociation between release and gene expression of gonadotropin alpha-subunit in gonadotropin-releasing hormone-stimulated alpha T3-1 cell line. The alpha T3-1 cell line which was derived by targeted tumorigenesis in transgenic mice [Windle et al. (1990) Mol. Endocrinol. 4, 597-603] possesses high-affinity binding sites for GnRH analogs coupled to enhanced phosphoinositide turnover and phospholipase D activity. Incubation of alpha T3-1 cells with [D-Trp6]-GnRH analog (GnRH-A) resulted in a rapid increase in gonadotropin alpha-subunit mRNA levels which was detected already at 30 min of incubation (0.1 nM GnRH-A, 3-fold, p < 0.01). The effect diminished with time to reach basal levels at about 12 h of incubation, with a secondary rise in alpha mRNA levels between 12 and 24 h of incubation. Addition of the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 ng/mL) or the Ca2+ ionophore ionomycin (1 microM) to alpha T3-1 cells also resulted in a rapid increase in alpha-subunit mRNA levels. Surprisingly, GnRH-induced alpha-subunit release was detected only after a lag of 4 h of incubation. Thus, dissociation between exocytosis and gene expression can be demonstrated in GnRH-stimulated alpha T3-1 cell line."} {"id": "PMID:1281430", "title": "The interaction of a glycosaminoglycan, heparin, with HIV-1 major envelope glycoprotein.", "content": "We demonstrate in vitro the occurrence of a specific but low-affinity interaction between soluble tetrameric rgp160 or soluble monomeric or tetrameric rgp120 and heparin-agarose (HA). This interaction is saturable, pH and temperature-dependent, and can be inhibited by soluble heparin, but not by soluble dextran. In buffer supplemented with 10 mM CaCl2, the C50 of soluble heparin, i.e., the concentration of soluble heparin which leads to 50% inhibition of the binding of [125I]rgp160 or of [125I]rgp120 to HA, is 1.1 x 10(-4) disaccharidic molar concentration for rgp160 and 3.2 x 10(-4) dissacharidic molar concentration for rgp120, which indicates low-affinity interactions. Upon chromatography on HA, [125I]rgp160 is repeatedly eluted as a retarded fraction when compared to the elution volume of [125I]rgp160-soluble heparin complex. Under the same experimental conditions, [125I]rgp120 is also eluted, but as a less retarded fraction than [125I]rgp160. Taken together, these results suggest that, at least part of the described anti HIV-1 activity of heparin might be mediated by interaction with HIV-1 major envelope glycoprotein.", "contents": "The interaction of a glycosaminoglycan, heparin, with HIV-1 major envelope glycoprotein. We demonstrate in vitro the occurrence of a specific but low-affinity interaction between soluble tetrameric rgp160 or soluble monomeric or tetrameric rgp120 and heparin-agarose (HA). This interaction is saturable, pH and temperature-dependent, and can be inhibited by soluble heparin, but not by soluble dextran. In buffer supplemented with 10 mM CaCl2, the C50 of soluble heparin, i.e., the concentration of soluble heparin which leads to 50% inhibition of the binding of [125I]rgp160 or of [125I]rgp120 to HA, is 1.1 x 10(-4) disaccharidic molar concentration for rgp160 and 3.2 x 10(-4) dissacharidic molar concentration for rgp120, which indicates low-affinity interactions. Upon chromatography on HA, [125I]rgp160 is repeatedly eluted as a retarded fraction when compared to the elution volume of [125I]rgp160-soluble heparin complex. Under the same experimental conditions, [125I]rgp120 is also eluted, but as a less retarded fraction than [125I]rgp160. Taken together, these results suggest that, at least part of the described anti HIV-1 activity of heparin might be mediated by interaction with HIV-1 major envelope glycoprotein."} {"id": "PMID:1281431", "title": "Maleylated human serum albumin inhibits HIV-1 infection in vitro.", "content": "Maleylated-human serum albumin (Mal-HSA) inhibited human immunodeficiency virus type-1 (HIV-1) infection of MT-4 cells in vitro. It was also found to inhibit the fusion between uninfected CD4+ cells (Molt-4 clone 8 cells) and HIV-1 infected cells (Molt-4/HIV-1) to form syncytia. To investigate the mechanism of the inhibition, a study was designed to determine whether Mal-HSA could bind to CD4+ cells. Mal-HSA could bind to both MT-4 cells and Molt-4 clone 8 cells with high affinity, Kd = 2.0 nM and Kd = 5.8 nM, respectively. However, Mal-HSA could neither inhibit anti CD4 antibody Leu 3a binding to Molt-4 clone 8 cells nor modulate the expression of CD4 molecules on the surface of the cells. Mal-HSA binding to Molt-4 clone 8 cells was completely inhibited by sulfated polysaccharides bearing anti-HIV activity, such as dextran sulfate, fucoidan and carrageenan. Other HIV-1 susceptible human T-cell lines, such as Molt-4, CEM-5, H-9 and HuT-78 cells, also have Mal-HSA binding sites showing a high affinity, Kd = 0.9 +/- 0.4 nM. Mal-HSA binding proteins of Molt-4 clone 8 cells were identified by ligand blotting as 155 and 220 kDa proteins. Unlike dextran sulfate, Mal-HSA could not inhibit reverse transcriptase activity of HIV-1. These results indicate that Mal-HSA inhibits HIV-1 infection and syncytia formation, and suggest that 155 and/or 220 kDa proteins of target cells are involved in HIV-1 adsorption and/or the membrane fusion between HIV-1 and target cells.", "contents": "Maleylated human serum albumin inhibits HIV-1 infection in vitro. Maleylated-human serum albumin (Mal-HSA) inhibited human immunodeficiency virus type-1 (HIV-1) infection of MT-4 cells in vitro. It was also found to inhibit the fusion between uninfected CD4+ cells (Molt-4 clone 8 cells) and HIV-1 infected cells (Molt-4/HIV-1) to form syncytia. To investigate the mechanism of the inhibition, a study was designed to determine whether Mal-HSA could bind to CD4+ cells. Mal-HSA could bind to both MT-4 cells and Molt-4 clone 8 cells with high affinity, Kd = 2.0 nM and Kd = 5.8 nM, respectively. However, Mal-HSA could neither inhibit anti CD4 antibody Leu 3a binding to Molt-4 clone 8 cells nor modulate the expression of CD4 molecules on the surface of the cells. Mal-HSA binding to Molt-4 clone 8 cells was completely inhibited by sulfated polysaccharides bearing anti-HIV activity, such as dextran sulfate, fucoidan and carrageenan. Other HIV-1 susceptible human T-cell lines, such as Molt-4, CEM-5, H-9 and HuT-78 cells, also have Mal-HSA binding sites showing a high affinity, Kd = 0.9 +/- 0.4 nM. Mal-HSA binding proteins of Molt-4 clone 8 cells were identified by ligand blotting as 155 and 220 kDa proteins. Unlike dextran sulfate, Mal-HSA could not inhibit reverse transcriptase activity of HIV-1. These results indicate that Mal-HSA inhibits HIV-1 infection and syncytia formation, and suggest that 155 and/or 220 kDa proteins of target cells are involved in HIV-1 adsorption and/or the membrane fusion between HIV-1 and target cells."} {"id": "PMID:1281433", "title": "Amyotrophic lateral sclerosis.", "content": "Amyotrophic lateral sclerosis (ALS) is a clinical entity differentiated during the last few years into definite, probable, possible and suspected ALS. There are many hypotheses trying to explain its genesis: slow virus hypothesis, trace elements, immunologic and trophic factors, excitotoxins, metabolic influences, DNA anomalies, and so on. It is necessary to differentiate ALS like syndromes and ALS variants. Some of the ALS like syndromes can be treated. Only the disease elaborated like that may be submitted to clinical therapeutical trials or molecular-genetic research. Palliative therapy is still necessary. It does not prolong life, it makes its quality better.", "contents": "Amyotrophic lateral sclerosis. Amyotrophic lateral sclerosis (ALS) is a clinical entity differentiated during the last few years into definite, probable, possible and suspected ALS. There are many hypotheses trying to explain its genesis: slow virus hypothesis, trace elements, immunologic and trophic factors, excitotoxins, metabolic influences, DNA anomalies, and so on. It is necessary to differentiate ALS like syndromes and ALS variants. Some of the ALS like syndromes can be treated. Only the disease elaborated like that may be submitted to clinical therapeutical trials or molecular-genetic research. Palliative therapy is still necessary. It does not prolong life, it makes its quality better."} {"id": "PMID:1281432", "title": "Imidazoles as well as thiolates in proteins bind technetium-99m.", "content": "99mTc is widely thought to directly bind proteins through thiolate groups of cysteine residues, resulting in Tc-cysteinyl-protein bonds. Chemical reduction of disulfide bonds in proteins is widely used to generate thiolates with the goal of increasing 99mTc binding. This strategy is used because most proteins contain no thiolates, but many do contain disulfide bonds. In this study, we have evaluated the hypothesis that imidazole groups of histidine are also involved in direct 99mTc binding to proteins. Human gamma-globulin was used as the model protein in these studies. The immunoglobulin was used (a) without reduction or was (b) treated with stannous ions to reduce disulfide bonds thereby increasing thiolate concentration. These proteins were used to evaluate the hypothesis that imidazole as well as thiolate groups bind Tc. The proteins were evaluated by (a) using free amino acids to compete with proteins for 99mTc and (b) by chemical modification of amino acid side chains. In addition, peptides known to contain either cysteine or histidine, but not both, were also successfully directly labeled with 99mTc. These results indicate that in proteins (and peptides) imidazole-containing groups as well as thiolate-containing groups bind Tc.", "contents": "Imidazoles as well as thiolates in proteins bind technetium-99m. 99mTc is widely thought to directly bind proteins through thiolate groups of cysteine residues, resulting in Tc-cysteinyl-protein bonds. Chemical reduction of disulfide bonds in proteins is widely used to generate thiolates with the goal of increasing 99mTc binding. This strategy is used because most proteins contain no thiolates, but many do contain disulfide bonds. In this study, we have evaluated the hypothesis that imidazole groups of histidine are also involved in direct 99mTc binding to proteins. Human gamma-globulin was used as the model protein in these studies. The immunoglobulin was used (a) without reduction or was (b) treated with stannous ions to reduce disulfide bonds thereby increasing thiolate concentration. These proteins were used to evaluate the hypothesis that imidazole as well as thiolate groups bind Tc. The proteins were evaluated by (a) using free amino acids to compete with proteins for 99mTc and (b) by chemical modification of amino acid side chains. In addition, peptides known to contain either cysteine or histidine, but not both, were also successfully directly labeled with 99mTc. These results indicate that in proteins (and peptides) imidazole-containing groups as well as thiolate-containing groups bind Tc."} {"id": "PMID:1281434", "title": "Phytohemagglutinin gene expression during seed development of the runner bean, Phaseolus coccineus.", "content": "The expression of phytohemagglutinin (PHA) genes was studied in various tissues during the development of the seeds of Phaseolus coccineus cv. Hammond's Dwarf Scarlet by means of northern hybridization and reverse transcription polymerase chain reaction (RT-PCR). The expression is highly development-dependent, starting in the late stage (cotyledons begin to fill the endosperm cavity, i.e. 17 to 24 days after pollination), and tissue-specific. The highest levels of PHA-mRNA are found in the cotyledons (at a very late stage), much lower levels in the embryo axis. Very low levels could be detected in earlier stages of the endosperm, the integument, the funiculus, and probably also in the embryo suspensor. Some PHA mRNA was found in the cotyledons of dry seeds, indicating the presence of undegraded transcripts in mature seeds.", "contents": "Phytohemagglutinin gene expression during seed development of the runner bean, Phaseolus coccineus. The expression of phytohemagglutinin (PHA) genes was studied in various tissues during the development of the seeds of Phaseolus coccineus cv. Hammond's Dwarf Scarlet by means of northern hybridization and reverse transcription polymerase chain reaction (RT-PCR). The expression is highly development-dependent, starting in the late stage (cotyledons begin to fill the endosperm cavity, i.e. 17 to 24 days after pollination), and tissue-specific. The highest levels of PHA-mRNA are found in the cotyledons (at a very late stage), much lower levels in the embryo axis. Very low levels could be detected in earlier stages of the endosperm, the integument, the funiculus, and probably also in the embryo suspensor. Some PHA mRNA was found in the cotyledons of dry seeds, indicating the presence of undegraded transcripts in mature seeds."} {"id": "PMID:1281435", "title": "Molecular characterization and expression of an isocitrate dehydrogenase from alfalfa (Medicago sativa L).", "content": "A putative isocitrate dehydrogenase (IDH) cDNA from alfalfa has been cloned and sequenced. The derived amino acid sequence of 433 residues contains the isocitrate and isopropylmalate dehydrogenase signatures, is 63% identical to yeast mitochondrial NADP-IDH and shares high sequence identity with peptides of pig heart NADP-IDH. The sequence contains a potential N-terminal leader with similarities to a thylakoid transit peptide. IDH transcripts and NADP-IDH activity were detected in all alfalfa tissues examined, their levels depending upon the tissue type and its developmental stage. Transcripts and enzymatic activity were not induced on exposure of cell suspension cultures to a fungal elicitor. IDH is encoded by a small gene family in alfalfa.", "contents": "Molecular characterization and expression of an isocitrate dehydrogenase from alfalfa (Medicago sativa L). A putative isocitrate dehydrogenase (IDH) cDNA from alfalfa has been cloned and sequenced. The derived amino acid sequence of 433 residues contains the isocitrate and isopropylmalate dehydrogenase signatures, is 63% identical to yeast mitochondrial NADP-IDH and shares high sequence identity with peptides of pig heart NADP-IDH. The sequence contains a potential N-terminal leader with similarities to a thylakoid transit peptide. IDH transcripts and NADP-IDH activity were detected in all alfalfa tissues examined, their levels depending upon the tissue type and its developmental stage. Transcripts and enzymatic activity were not induced on exposure of cell suspension cultures to a fungal elicitor. IDH is encoded by a small gene family in alfalfa."} {"id": "PMID:1281436", "title": "Cloning, partial sequencing and expression of a cDNA coding for branching enzyme in cassava.", "content": "Branching enzyme is involved in the synthesis of amylopectin in plant reserve starch. A cDNA coding for cassava (Manihot esculenta Crantz) branching enzyme was cloned from a lambda gt11 cDNA library using a potato cDNA probe. The cloned cDNA was partially sequenced. The sequence data confirmed the identity of the clone when compared to that of potato, the homology being ca. 80% at the nucleotide level and 85% at the amino acid level. Furthermore, the cloned cassava cDNA was able to restore branching enzyme activity in a branching enzyme deficient Escherichia coli mutant. Results of the Southern analysis suggested that there is a single gene for this particular branching enzyme in the cassava genome. Study of expression patterns by northern hybridization showed that the gene is highly expressed in tubers. The transcript is detectable in stem and petiole, but not in leaves. In roots, the mRNA is hardly present. The expression levels at different stages of tuber growth are similar with exception of very young tubers in which it is relatively low. It is also shown that there is a difference in the level of branching enzyme expression between different cassava genotypes.", "contents": "Cloning, partial sequencing and expression of a cDNA coding for branching enzyme in cassava. Branching enzyme is involved in the synthesis of amylopectin in plant reserve starch. A cDNA coding for cassava (Manihot esculenta Crantz) branching enzyme was cloned from a lambda gt11 cDNA library using a potato cDNA probe. The cloned cDNA was partially sequenced. The sequence data confirmed the identity of the clone when compared to that of potato, the homology being ca. 80% at the nucleotide level and 85% at the amino acid level. Furthermore, the cloned cassava cDNA was able to restore branching enzyme activity in a branching enzyme deficient Escherichia coli mutant. Results of the Southern analysis suggested that there is a single gene for this particular branching enzyme in the cassava genome. Study of expression patterns by northern hybridization showed that the gene is highly expressed in tubers. The transcript is detectable in stem and petiole, but not in leaves. In roots, the mRNA is hardly present. The expression levels at different stages of tuber growth are similar with exception of very young tubers in which it is relatively low. It is also shown that there is a difference in the level of branching enzyme expression between different cassava genotypes."} {"id": "PMID:1281437", "title": "Cellulase and polygalacturonase involvement in the abscission of leaf and fruit explants of peach.", "content": "Ethylene-induced abscission in leaf and fruit explants of peach involves different enzymes. In leaves abscission is accompanied by increased occurrence of cellulase forms differing in isoelectric point (pI 6.5 and 9.5). A polypeptide with a molecular mass of 51 kDa gives in a western blot a strong cross-reaction with an antibody raised against a maturation cellulase from avocado fruit. Cellulase activity is also found in abscising fruit explants but the amount is very low compared to that of the leaf explants. A northern analysis with a cellulase clone from avocado reveals the presence of two hybridizing mRNAs with a size of 2.2 kb and 1.8 kb, respectively. The steady-state level of the 2.2 kb mRNA is significantly increased by treatment with ethylene. Polygalacturonases are not detected in abscising leaves, but are strongly induced by ethylene in fruit explants. Of the three forms found, two are exopolygalacturonases while the third is an endoenzyme. Ethylene activates preferentially the endoenzyme and the basic exoenzyme but depresses the acid exopolygalacturonases. A northern analysis carried out with a cDNA coding for tomato endopolygalacturonase shows hybridization only with one endopolygalacturonase mRNA form in the fruit abscission zone. Treatment with ethylene causes an increase in the steady-state level of this mRNA. The differences in the enzyme patterns observed in fruit and leaf abscission zones and a differential enzyme induction suggest the feasibility to regulate fruit abscission in peach with the aid of antisense RNA genes.", "contents": "Cellulase and polygalacturonase involvement in the abscission of leaf and fruit explants of peach. Ethylene-induced abscission in leaf and fruit explants of peach involves different enzymes. In leaves abscission is accompanied by increased occurrence of cellulase forms differing in isoelectric point (pI 6.5 and 9.5). A polypeptide with a molecular mass of 51 kDa gives in a western blot a strong cross-reaction with an antibody raised against a maturation cellulase from avocado fruit. Cellulase activity is also found in abscising fruit explants but the amount is very low compared to that of the leaf explants. A northern analysis with a cellulase clone from avocado reveals the presence of two hybridizing mRNAs with a size of 2.2 kb and 1.8 kb, respectively. The steady-state level of the 2.2 kb mRNA is significantly increased by treatment with ethylene. Polygalacturonases are not detected in abscising leaves, but are strongly induced by ethylene in fruit explants. Of the three forms found, two are exopolygalacturonases while the third is an endoenzyme. Ethylene activates preferentially the endoenzyme and the basic exoenzyme but depresses the acid exopolygalacturonases. A northern analysis carried out with a cDNA coding for tomato endopolygalacturonase shows hybridization only with one endopolygalacturonase mRNA form in the fruit abscission zone. Treatment with ethylene causes an increase in the steady-state level of this mRNA. The differences in the enzyme patterns observed in fruit and leaf abscission zones and a differential enzyme induction suggest the feasibility to regulate fruit abscission in peach with the aid of antisense RNA genes."} {"id": "PMID:1281438", "title": "Isolation and analysis of a genomic clone encoding a pokeweed antiviral protein.", "content": "Partial cDNAs encoding a pokeweed antiviral protein were obtained by polymerase chain reaction from the poly(A)+ RNA of seeds, leaves, and roots using two specific primers based on the amino acid sequence of a pokeweed antiviral protein from the seeds (PAP-S). Using the cDNAs as a radioactive probe, 17 and 39 positive plaques were isolated from libraries containing the genomic DNA of Phytolacca americana digested with Bam HI partially and completely, respectively. The plaques were grouped into nine types by Southern hybridization. The type alpha genomic clone encodes a protein of 294 amino acids. Its amino acid sequence is similar but not identical to that of PAP-S. A comparison of the two amino acid sequences suggested that the deduced protein contains extrapeptides of 24 and 9 amino acids at the NH2 and the COOH terminals, respectively. The putative protein was expressed in Escherichia coli and shown to depurinate the specific adenine of wheat 25S rRNA, indicating that the protein encoded by a type alpha genomic clone is a functional protein exhibiting RNA N-glycosidase activity.", "contents": "Isolation and analysis of a genomic clone encoding a pokeweed antiviral protein. Partial cDNAs encoding a pokeweed antiviral protein were obtained by polymerase chain reaction from the poly(A)+ RNA of seeds, leaves, and roots using two specific primers based on the amino acid sequence of a pokeweed antiviral protein from the seeds (PAP-S). Using the cDNAs as a radioactive probe, 17 and 39 positive plaques were isolated from libraries containing the genomic DNA of Phytolacca americana digested with Bam HI partially and completely, respectively. The plaques were grouped into nine types by Southern hybridization. The type alpha genomic clone encodes a protein of 294 amino acids. Its amino acid sequence is similar but not identical to that of PAP-S. A comparison of the two amino acid sequences suggested that the deduced protein contains extrapeptides of 24 and 9 amino acids at the NH2 and the COOH terminals, respectively. The putative protein was expressed in Escherichia coli and shown to depurinate the specific adenine of wheat 25S rRNA, indicating that the protein encoded by a type alpha genomic clone is a functional protein exhibiting RNA N-glycosidase activity."} {"id": "PMID:1281439", "title": "Ubiquitin genes are differentially regulated in protoplast-derived cultures of Nicotiana sylvestris and in response to various stresses.", "content": "Four ubiquitin mRNA size classes were found to be differentially regulated in mesophyll protoplast-derived cultures of Nicotiana sylvestris. Three mRNA families of 1.9, 1.6 and 1.35 kb were expressed as soon as protoplasts were isolated. The 1.9 and 1.6 kb size classes were transiently expressed during the first hours of culture, whereas the level of expression of the 1.35 kb size class was maintained as long as cells kept dividing. A 0.7 kb mRNA size class started to be expressed just before the first divisions were observed. cDNAs corresponding to each of these families were isolated from a 6-h-old protoplast cDNA library and characterized. The 1.9, 1.6 and 1.35 kb mRNAs thus encode 7- or more, 6- and 5-mers, respectively, of ubiquitin whereas the 0.7 kb mRNAs encode a monomer of ubiquitin fused to a carboxyl extension protein of 52 amino acids. The expression of ubiquitin genes was studied, using probes specific for each of these transcript families, during protoplast culture and, for comparison, after various stresses including heat shock, HgCl2 treatment, a viral infection giving rise to a hypersensitive reaction, and an Agrobacterium tumefaciens infection which resulted in tumour formation. The 1.9 and 1.6 kb mRNA size classes were found to be stress-regulated, the 0.7 kb mRNA size class developmentally regulated and the 1.35 kb size class both stress- and developmentally regulated.", "contents": "Ubiquitin genes are differentially regulated in protoplast-derived cultures of Nicotiana sylvestris and in response to various stresses. Four ubiquitin mRNA size classes were found to be differentially regulated in mesophyll protoplast-derived cultures of Nicotiana sylvestris. Three mRNA families of 1.9, 1.6 and 1.35 kb were expressed as soon as protoplasts were isolated. The 1.9 and 1.6 kb size classes were transiently expressed during the first hours of culture, whereas the level of expression of the 1.35 kb size class was maintained as long as cells kept dividing. A 0.7 kb mRNA size class started to be expressed just before the first divisions were observed. cDNAs corresponding to each of these families were isolated from a 6-h-old protoplast cDNA library and characterized. The 1.9, 1.6 and 1.35 kb mRNAs thus encode 7- or more, 6- and 5-mers, respectively, of ubiquitin whereas the 0.7 kb mRNAs encode a monomer of ubiquitin fused to a carboxyl extension protein of 52 amino acids. The expression of ubiquitin genes was studied, using probes specific for each of these transcript families, during protoplast culture and, for comparison, after various stresses including heat shock, HgCl2 treatment, a viral infection giving rise to a hypersensitive reaction, and an Agrobacterium tumefaciens infection which resulted in tumour formation. The 1.9 and 1.6 kb mRNA size classes were found to be stress-regulated, the 0.7 kb mRNA size class developmentally regulated and the 1.35 kb size class both stress- and developmentally regulated."} {"id": "PMID:1281441", "title": "[Sparteine and tedisamil inhibit chloride channels in pulmonary epithelial cells isolated from patients with cystic fibrosis].", "content": "Chloride current was measured in cells isolated from the pulmonary epithelium of patients with cystic fibrosis. By applying the whole cell patch clamp method three types of chloride current were identified, i.e. a time-dependent, an activating with time, and an inactivating with time. The time-dependent component of ICl proved to be DIDS sensitive. The effect of the potassium current blocker sparteine and its analogue tedisamil on ICl was tested. both substances were found to be chloride current inhibitors, yet the effectiveness of sparteine was 10(4) times higher.", "contents": "[Sparteine and tedisamil inhibit chloride channels in pulmonary epithelial cells isolated from patients with cystic fibrosis]. Chloride current was measured in cells isolated from the pulmonary epithelium of patients with cystic fibrosis. By applying the whole cell patch clamp method three types of chloride current were identified, i.e. a time-dependent, an activating with time, and an inactivating with time. The time-dependent component of ICl proved to be DIDS sensitive. The effect of the potassium current blocker sparteine and its analogue tedisamil on ICl was tested. both substances were found to be chloride current inhibitors, yet the effectiveness of sparteine was 10(4) times higher."} {"id": "PMID:1281442", "title": "Egg and milk allergy in adults: comparison between fresh foods and commercial allergen extracts in skin prick test and histamine release from basophils.", "content": "The ability of skin prick test (SPT) and histamine release from basophils (HR) to diagnose clinical type I allergy to egg and milk was investigated as compared with double-blind, placebo-controlled food challenge (DBPCFC) in 17 adults suspected of type I egg and/or milk allergy. In both SPT and HR, commercial allergen extracts commonly used for SPT were compared with fresh, standardized foods. With commercial extracts the overall sensitivities of SPT and HR were 0.75 and 0.56 respectively, and none of the tests showed concordance with DBPCFC. With fresh, standardized foods the overall sensitivities of SPT and HR were 1.00 and 0.89 respectively, and both tests now showed a significant concordance with DBPCFC (P < 0.05). Specificity was only slightly improved in SPT, and unchanged in HR. Thus, the use of fresh, standardized foods significantly improved the outcome of both tests, as regards to sensitivity and concordance with DBPCFC. The diagnostic ability of SPT and HR appear to be strongly influenced by the allergen quality.", "contents": "Egg and milk allergy in adults: comparison between fresh foods and commercial allergen extracts in skin prick test and histamine release from basophils. The ability of skin prick test (SPT) and histamine release from basophils (HR) to diagnose clinical type I allergy to egg and milk was investigated as compared with double-blind, placebo-controlled food challenge (DBPCFC) in 17 adults suspected of type I egg and/or milk allergy. In both SPT and HR, commercial allergen extracts commonly used for SPT were compared with fresh, standardized foods. With commercial extracts the overall sensitivities of SPT and HR were 0.75 and 0.56 respectively, and none of the tests showed concordance with DBPCFC. With fresh, standardized foods the overall sensitivities of SPT and HR were 1.00 and 0.89 respectively, and both tests now showed a significant concordance with DBPCFC (P < 0.05). Specificity was only slightly improved in SPT, and unchanged in HR. Thus, the use of fresh, standardized foods significantly improved the outcome of both tests, as regards to sensitivity and concordance with DBPCFC. The diagnostic ability of SPT and HR appear to be strongly influenced by the allergen quality."} {"id": "PMID:1281443", "title": "Characterization of transcripts expressed from nitrogenase-3 structural genes of Azotobacter vinelandii.", "content": "Five major anfH-hybridizing mRNA species accumulated in Azobacter vinelandii cells derepressed for nitrogenase-3 (an alternative nitrogenase, which appears to lack Mo and V). Using anfH-, anfD-, anfG-, anfK-, and orflorf2-specific probes and mutant strains of A. vinelandii these mRNA species have been identified as encoding anfHDGKorflorf2 (6.0 kb), anfHDGK (4.3 kb), anfHD (2.6 kb), vnfHorfFd (1.3 kb), and vnfH and (or) anfH (1.0 kb). A 0.6-kb mRNA species, which hybridized only to the orflorf2-specific probe, and a 3.5-kb mRNA species, which hybridized to anfD or anfK, also accumulated under these conditions. Northern blot analysis and S1 nuclease mapping indicate that transcription of the anf structural gene cluster initiates at a unique nif consensus promoter situated 127 base pairs upstream from the anfH coding region. Observation of anfH-hybridizing mRNA species that accumulate in strains derepressed for nitrogen fixation demonstrates that transcription of the anfHDGKorflorf2 cluster is normally repressed by Mo, V, and NH4+, whereas transcription of the vnfHorfFd cluster does not require the presence of V and is repressed only by Mo, but not NH4+. Analysis of the accumulation of mRNAs in a tungsten-tolerant strain revealed that Mo and V repression of anf transcription must occur by different mechanisms.", "contents": "Characterization of transcripts expressed from nitrogenase-3 structural genes of Azotobacter vinelandii. Five major anfH-hybridizing mRNA species accumulated in Azobacter vinelandii cells derepressed for nitrogenase-3 (an alternative nitrogenase, which appears to lack Mo and V). Using anfH-, anfD-, anfG-, anfK-, and orflorf2-specific probes and mutant strains of A. vinelandii these mRNA species have been identified as encoding anfHDGKorflorf2 (6.0 kb), anfHDGK (4.3 kb), anfHD (2.6 kb), vnfHorfFd (1.3 kb), and vnfH and (or) anfH (1.0 kb). A 0.6-kb mRNA species, which hybridized only to the orflorf2-specific probe, and a 3.5-kb mRNA species, which hybridized to anfD or anfK, also accumulated under these conditions. Northern blot analysis and S1 nuclease mapping indicate that transcription of the anf structural gene cluster initiates at a unique nif consensus promoter situated 127 base pairs upstream from the anfH coding region. Observation of anfH-hybridizing mRNA species that accumulate in strains derepressed for nitrogen fixation demonstrates that transcription of the anfHDGKorflorf2 cluster is normally repressed by Mo, V, and NH4+, whereas transcription of the vnfHorfFd cluster does not require the presence of V and is repressed only by Mo, but not NH4+. Analysis of the accumulation of mRNAs in a tungsten-tolerant strain revealed that Mo and V repression of anf transcription must occur by different mechanisms."} {"id": "PMID:1281444", "title": "Receptors for toxic shock syndrome toxin-1 and staphylococcal enterotoxin A on human blood monocytes.", "content": "Staphylococcal toxic shock syndrome toxin-1 (TSST-1) as well as staphylococcal enterotoxin A (SEA) and B (SEB) have recently been shown to bind directly to the class II major histocompatibility antigen, HLA-DR. Whereas others have characterized TSST-1 and SEA binding to HLA-DR on transfected L cells or B lymphoma cell lines, we sought evidence for direct binding of TSST-1 and SEA to HLA-DR on purified human monocytes. A single class of high-affinity receptors was found for both TSST-1 (dissociation constant (Kd) 40 nM, 3.4 x 10(4) receptors per cell) and SEA (Kd 12 nM, 3.2 x 10(4) receptors per cell) on normal human monocytes. Affinity cross-linking of 125I-labeled toxins to monocytes revealed the presence of two membrane protein subunits with molecular masses consistent with the alpha and beta chains of human HLA-DR (35 and 28 kDa, respectively). The anti-HLA-DR monoclonal antibody L243, but not L203 or 2.06, inhibited radiolabeled toxin binding to human monocytes and neutralized the mitogenic response of human T lymphocytes to both toxins. However, L243 was consistently more effective in blocking radiolabeled TSST-1 than SEA binding to human monocytes from the same donors, suggesting that TSST-1 and SEA may be binding to overlapping epitopes rather than to the same epitope on HLA-DR. Because TSST-1 and SEB bind to distinct epitopes on HLA-DR and because SEA cross competes with both TSST-1 and SEB on the HLA-DR receptor, we postulate that SEA occupies a binding site within HLA-DR that overlaps both TSST-1 and SEB.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Receptors for toxic shock syndrome toxin-1 and staphylococcal enterotoxin A on human blood monocytes. Staphylococcal toxic shock syndrome toxin-1 (TSST-1) as well as staphylococcal enterotoxin A (SEA) and B (SEB) have recently been shown to bind directly to the class II major histocompatibility antigen, HLA-DR. Whereas others have characterized TSST-1 and SEA binding to HLA-DR on transfected L cells or B lymphoma cell lines, we sought evidence for direct binding of TSST-1 and SEA to HLA-DR on purified human monocytes. A single class of high-affinity receptors was found for both TSST-1 (dissociation constant (Kd) 40 nM, 3.4 x 10(4) receptors per cell) and SEA (Kd 12 nM, 3.2 x 10(4) receptors per cell) on normal human monocytes. Affinity cross-linking of 125I-labeled toxins to monocytes revealed the presence of two membrane protein subunits with molecular masses consistent with the alpha and beta chains of human HLA-DR (35 and 28 kDa, respectively). The anti-HLA-DR monoclonal antibody L243, but not L203 or 2.06, inhibited radiolabeled toxin binding to human monocytes and neutralized the mitogenic response of human T lymphocytes to both toxins. However, L243 was consistently more effective in blocking radiolabeled TSST-1 than SEA binding to human monocytes from the same donors, suggesting that TSST-1 and SEA may be binding to overlapping epitopes rather than to the same epitope on HLA-DR. Because TSST-1 and SEB bind to distinct epitopes on HLA-DR and because SEA cross competes with both TSST-1 and SEB on the HLA-DR receptor, we postulate that SEA occupies a binding site within HLA-DR that overlaps both TSST-1 and SEB.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281445", "title": "Screening of cases of acute flaccid paralysis for poliomyelitis eradication: ways to improve specificity.", "content": "The Pan American Health Organization in 1985 adopted an initiative to eradicate poliomyelitis from the Western Hemisphere. In 1990, over 2000 cases of acute flaccid paralysis (AFP) were reported in this region, of which < 1% were determined to be caused by wild poliovirus. At present, the eradication programme uses AFP as the criterion for surveillance of children aged < 15 years; this is 100% sensitive, but not specific. To minimize unnecessary diagnostic investigations, we studied all 4333 cases of AFP reported to the programme during 1989 and 1990 in order to develop more efficient operational screening criteria for cases of AFP. Among children with AFP, the use of criteria such as age < 6 years and either presence of fever at the onset of paralysis or a < 4-day period for complete development of paralysis resulted in a sensitivity of 96% (95% C.I. 90-103%) and specificity of 49% (C.I. 47-52%). With criteria of age < 6 years and fever present at the onset of paralysis the sensitivity was 75% (C.I. 61-89%) and specificity was 73% (C.I. 71-75%). These results suggest that by screening young children with AFP who either had fever at the onset or showed a rapid progression of paralysis, the number of cases of AFP requiring investigation can be reduced by one half, with minimal compromise in the sensitivity of confirmed poliomyelitis case detection.", "contents": "Screening of cases of acute flaccid paralysis for poliomyelitis eradication: ways to improve specificity. The Pan American Health Organization in 1985 adopted an initiative to eradicate poliomyelitis from the Western Hemisphere. In 1990, over 2000 cases of acute flaccid paralysis (AFP) were reported in this region, of which < 1% were determined to be caused by wild poliovirus. At present, the eradication programme uses AFP as the criterion for surveillance of children aged < 15 years; this is 100% sensitive, but not specific. To minimize unnecessary diagnostic investigations, we studied all 4333 cases of AFP reported to the programme during 1989 and 1990 in order to develop more efficient operational screening criteria for cases of AFP. Among children with AFP, the use of criteria such as age < 6 years and either presence of fever at the onset of paralysis or a < 4-day period for complete development of paralysis resulted in a sensitivity of 96% (95% C.I. 90-103%) and specificity of 49% (C.I. 47-52%). With criteria of age < 6 years and fever present at the onset of paralysis the sensitivity was 75% (C.I. 61-89%) and specificity was 73% (C.I. 71-75%). These results suggest that by screening young children with AFP who either had fever at the onset or showed a rapid progression of paralysis, the number of cases of AFP requiring investigation can be reduced by one half, with minimal compromise in the sensitivity of confirmed poliomyelitis case detection."} {"id": "PMID:1281446", "title": "The use of granulocyte colony-stimulating factor to shorten the interval between cycles of mitomycin C, vindesine, and cisplatin chemotherapy in non-small-cell lung cancer.", "content": "We investigated the possibility of shortening the interval between courses of the commonly prescribed 28-day MVP (mitomycin C, vindesine, and cisplatin) regimen in patients with non-small-cell lung cancer (NSCLC). We conducted a nonrandomized phase II study using recombinant human granulocyte colony-stimulating factor (G-CSF, Chugai) to explore the possibility of shortening the cycle length to 21 days and compared the results with those obtained in historical controls who had received the standard 28-day regimen. A total of 40 patients, 37 of whom were evaluable, were entered in the 21-day treatment group of the trial and were compared with 38 historical controls who had received standard 28-day cycles of MVP at our institution. Patients in the 21-day group received mitomycin C at 8 mg/m2 on day 1, vindesine at 3 mg/m2 on days 1 and 8, and cisplatin at 80 mg/m2 on day 1, with the schedule being repeated every 21 days. Controls had received the same regimen, albeit at 28-day intervals. G-CSF was given s.c. to the patients in the 21-day group at a daily dose of 2 micrograms/kg from day 2 to day 21 of every MVP cycle. The administration of G-CSF to these patients accelerated neutrophil recovery as compared with that observed in the historical controls. Significant differences were found between the two groups in terms of mean neutrophil nadirs (2666/microliters in the first cycle and 1369/microliters in the second for the G-CSF group vs 416/microliters in the first cycle and 685/microliters in the second cycle for the control group; P < 0.0001) and the mean duration of neutropenia (< or = 1000/microliters; 1.0 day in the first cycle and 1.7 days in the second for the G-CSF group vs 8.0 days in the first cycle and 6.9 days in the second for the control group; P < 0.0001). This enabled 32 (86%) of 37 patients in the G-CSF group to complete > or = 2 cycles on schedule. In 10 patients, the bone marrow aspirates taken after G-CSF administration showed increases in band neutrophil and myelocyte percentages. In conclusion, MVP treatment of patients with NSCLC at 21-day intervals is possible with the support of G-CSF.", "contents": "The use of granulocyte colony-stimulating factor to shorten the interval between cycles of mitomycin C, vindesine, and cisplatin chemotherapy in non-small-cell lung cancer. We investigated the possibility of shortening the interval between courses of the commonly prescribed 28-day MVP (mitomycin C, vindesine, and cisplatin) regimen in patients with non-small-cell lung cancer (NSCLC). We conducted a nonrandomized phase II study using recombinant human granulocyte colony-stimulating factor (G-CSF, Chugai) to explore the possibility of shortening the cycle length to 21 days and compared the results with those obtained in historical controls who had received the standard 28-day regimen. A total of 40 patients, 37 of whom were evaluable, were entered in the 21-day treatment group of the trial and were compared with 38 historical controls who had received standard 28-day cycles of MVP at our institution. Patients in the 21-day group received mitomycin C at 8 mg/m2 on day 1, vindesine at 3 mg/m2 on days 1 and 8, and cisplatin at 80 mg/m2 on day 1, with the schedule being repeated every 21 days. Controls had received the same regimen, albeit at 28-day intervals. G-CSF was given s.c. to the patients in the 21-day group at a daily dose of 2 micrograms/kg from day 2 to day 21 of every MVP cycle. The administration of G-CSF to these patients accelerated neutrophil recovery as compared with that observed in the historical controls. Significant differences were found between the two groups in terms of mean neutrophil nadirs (2666/microliters in the first cycle and 1369/microliters in the second for the G-CSF group vs 416/microliters in the first cycle and 685/microliters in the second cycle for the control group; P < 0.0001) and the mean duration of neutropenia (< or = 1000/microliters; 1.0 day in the first cycle and 1.7 days in the second for the G-CSF group vs 8.0 days in the first cycle and 6.9 days in the second for the control group; P < 0.0001). This enabled 32 (86%) of 37 patients in the G-CSF group to complete > or = 2 cycles on schedule. In 10 patients, the bone marrow aspirates taken after G-CSF administration showed increases in band neutrophil and myelocyte percentages. In conclusion, MVP treatment of patients with NSCLC at 21-day intervals is possible with the support of G-CSF."} {"id": "PMID:1281447", "title": "Rat model of perchloroethylene-induced renal dysfunctions.", "content": "To investigate whether perchloroethylene (PCE) can induce renal disturbances and to compare morphological alterations with functional data, two groups of 12 male and female Fischer-344 mature rats were treated daily with PCE (500 mg/kg body wt in corn oil, p.o.) for 4 weeks. Sex- and age-matched control groups received corn oil only. Weekly, the urinary excretion of albumin (Alb), alpha 2 mu-globulin (alpha 2 mu) and retinol-binding protein (RBP) was measured in 24-hr urine samples using immunoassays specific for rat proteins. N-acetylglucosaminidase (NAG) activity was measured by a colorimetric assay. Electrophoretic analysis of proteinuria included SDS-PAGE and isoelectric-focusing of Alb purified from serum and urine. Weekly histopathology comprised light and electron microscopy. In the male rat, a trend toward progressive albuminuria (up to 15 times the pair-fed controls) was observed, together with transient increases in alpha 2 mu and NAG; RBP showed a twofold increase at the end of treatment. Histopathology failed to demonstrate glomerular changes, whereas it displayed alpha 2 mu accumulation and mild lesions in the S2 segment of proximal tubules. Thus, in the male rat, the selective damage to S2 was associated with \"glomerular\" proteinuria, the alpha 2 mu cortical content being closely correlated with albuminuria (n = 9, r = 0.92, P < 0.001). In the female rat, only minor, although statistically significant (P < 0.05), increases were recorded for Alb, whereas urinary alpha 2 mu reached up to four times the control values. As a whole, these findings suggest that PCE, like other hydrocarbons, selectively affects the tubular segment S2 in the rat. A competition with alpha 2 mu for tubular uptake could explain enhanced albuminuria. Owing to the species specificity of alpha 2 mu, caution should be exercised in extrapolating these findings to man.", "contents": "Rat model of perchloroethylene-induced renal dysfunctions. To investigate whether perchloroethylene (PCE) can induce renal disturbances and to compare morphological alterations with functional data, two groups of 12 male and female Fischer-344 mature rats were treated daily with PCE (500 mg/kg body wt in corn oil, p.o.) for 4 weeks. Sex- and age-matched control groups received corn oil only. Weekly, the urinary excretion of albumin (Alb), alpha 2 mu-globulin (alpha 2 mu) and retinol-binding protein (RBP) was measured in 24-hr urine samples using immunoassays specific for rat proteins. N-acetylglucosaminidase (NAG) activity was measured by a colorimetric assay. Electrophoretic analysis of proteinuria included SDS-PAGE and isoelectric-focusing of Alb purified from serum and urine. Weekly histopathology comprised light and electron microscopy. In the male rat, a trend toward progressive albuminuria (up to 15 times the pair-fed controls) was observed, together with transient increases in alpha 2 mu and NAG; RBP showed a twofold increase at the end of treatment. Histopathology failed to demonstrate glomerular changes, whereas it displayed alpha 2 mu accumulation and mild lesions in the S2 segment of proximal tubules. Thus, in the male rat, the selective damage to S2 was associated with \"glomerular\" proteinuria, the alpha 2 mu cortical content being closely correlated with albuminuria (n = 9, r = 0.92, P < 0.001). In the female rat, only minor, although statistically significant (P < 0.05), increases were recorded for Alb, whereas urinary alpha 2 mu reached up to four times the control values. As a whole, these findings suggest that PCE, like other hydrocarbons, selectively affects the tubular segment S2 in the rat. A competition with alpha 2 mu for tubular uptake could explain enhanced albuminuria. Owing to the species specificity of alpha 2 mu, caution should be exercised in extrapolating these findings to man."} {"id": "PMID:1281448", "title": "Induction of hepatic CYP1A in male F344/NCr rats by dietary exposure to Aroclor 1254: examination of immunochemical, RNA, catalytic, and pharmacokinetic endpoints.", "content": "Male F344/NCr rats were exposed to low dietary concentrations of Aroclor 1254 (0-33 ppm) for 7 days, following which the induction of selected hepatic drug metabolizing enzymes was monitored. CYP1A1, measured indirectly by assaying the O-dealkylation of ethoxyresorufin in 9000 g supernatants, was increased 1.5-, 3-, 8-, and 37-fold following 7 days of exposure to 1.0, 3.3, 10, and 33 ppm Aroclor, respectively. In contrast, the O-dealkylation of benzyloxyresorufin, an indirect measure of CYP2B1 activity, was increased approximately 4-fold following exposure to 33 ppm dietary Aroclor. Measurement of the non-P450-mediated activities epoxide hydrolase, DT-diaphorase, and aldehyde dehydrogenase (NADP+, benzaldehyde) revealed < 4-fold inductions following feeding of 33 ppm Aroclor. In view of the relatively high sensitivity of the CYP1A-specific catalytic endpoint as a biomarker for Aroclor exposure, alternative endpoints for detecting induction of this subfamily of P450 were also examined. The extent of in vivo CYP1A induction was assessed by measuring serum concentrations of zoxazolamine 150 min following an intraperitoneal dose of 100 mg/kg body wt. Slight decreases in serum zoxazolamine concentration were observed in rats exposed to as little as 1.0 ppm dietary Aroclor 1254, while profound decreases were seen in rats exposed to > or = to 10 ppm Aroclor. Immunodetection of CYP1A1 protein, with a monoclonal antibody directed against this cytochrome, revealed a 2.9-fold increase in rats exposed to as little as 1.0 ppm Aroclor, and approximately 10- and 44-fold increases following exposure to 3.3 and 10 ppm dietary Aroclor, respectively. Increases in total hepatocellular RNA coding for CYP1A1 and CYP1A2, quantified by hybridization to specific oligonucleotide probes, corresponded well to the increases in hepatic O-dealkylase activity for ethoxyresorufin (CYP1A1) and methoxyresorufin (CYP1A2), respectively. Thus, CYP1A induction, directly or indirectly measured with a variety of endpoints, represents a highly sensitive biomarker for exposure to relatively low doses of Aroclor 1254 in the rat.", "contents": "Induction of hepatic CYP1A in male F344/NCr rats by dietary exposure to Aroclor 1254: examination of immunochemical, RNA, catalytic, and pharmacokinetic endpoints. Male F344/NCr rats were exposed to low dietary concentrations of Aroclor 1254 (0-33 ppm) for 7 days, following which the induction of selected hepatic drug metabolizing enzymes was monitored. CYP1A1, measured indirectly by assaying the O-dealkylation of ethoxyresorufin in 9000 g supernatants, was increased 1.5-, 3-, 8-, and 37-fold following 7 days of exposure to 1.0, 3.3, 10, and 33 ppm Aroclor, respectively. In contrast, the O-dealkylation of benzyloxyresorufin, an indirect measure of CYP2B1 activity, was increased approximately 4-fold following exposure to 33 ppm dietary Aroclor. Measurement of the non-P450-mediated activities epoxide hydrolase, DT-diaphorase, and aldehyde dehydrogenase (NADP+, benzaldehyde) revealed < 4-fold inductions following feeding of 33 ppm Aroclor. In view of the relatively high sensitivity of the CYP1A-specific catalytic endpoint as a biomarker for Aroclor exposure, alternative endpoints for detecting induction of this subfamily of P450 were also examined. The extent of in vivo CYP1A induction was assessed by measuring serum concentrations of zoxazolamine 150 min following an intraperitoneal dose of 100 mg/kg body wt. Slight decreases in serum zoxazolamine concentration were observed in rats exposed to as little as 1.0 ppm dietary Aroclor 1254, while profound decreases were seen in rats exposed to > or = to 10 ppm Aroclor. Immunodetection of CYP1A1 protein, with a monoclonal antibody directed against this cytochrome, revealed a 2.9-fold increase in rats exposed to as little as 1.0 ppm Aroclor, and approximately 10- and 44-fold increases following exposure to 3.3 and 10 ppm dietary Aroclor, respectively. Increases in total hepatocellular RNA coding for CYP1A1 and CYP1A2, quantified by hybridization to specific oligonucleotide probes, corresponded well to the increases in hepatic O-dealkylase activity for ethoxyresorufin (CYP1A1) and methoxyresorufin (CYP1A2), respectively. Thus, CYP1A induction, directly or indirectly measured with a variety of endpoints, represents a highly sensitive biomarker for exposure to relatively low doses of Aroclor 1254 in the rat."} {"id": "PMID:1281449", "title": "Phosphorylation of CD44 in vivo requires both Ser323 and Ser325, but does not regulate membrane localization or cytoskeletal interaction in epithelial cells.", "content": "CD44 has been implicated to play an important role in a diverse range of physiological processes, which involve cell-matrix recognition, cell-cell adhesion and cell motility. There is increasing evidence that the highly conserved intracellular domain of CD44 may be involved in influencing these activities. CD44 is phosphorylated in vivo on serine residue(s). In view of the importance that phosphorylation has been accorded in a multitude of cellular regulatory processes, we have investigated the role of phosphorylation in the control of CD44. In this report we identify the sites of human CD44 phosphorylation by mutating the three conserved cytoplasmic serine residues. We show that both Ser323 and Ser325, but not Ser316, are required for phosphorylation in vivo and demonstrate that this event is not stimulated by phorbol esters. Clonal MDCK cell lines expressing both the single and double CD44 phosphorylation mutants have been generated. These cell lines have been used to directly assess the role of phosphorylation on CD44 localization in polarized epithelial cells and its association with the cytoskeleton.", "contents": "Phosphorylation of CD44 in vivo requires both Ser323 and Ser325, but does not regulate membrane localization or cytoskeletal interaction in epithelial cells. CD44 has been implicated to play an important role in a diverse range of physiological processes, which involve cell-matrix recognition, cell-cell adhesion and cell motility. There is increasing evidence that the highly conserved intracellular domain of CD44 may be involved in influencing these activities. CD44 is phosphorylated in vivo on serine residue(s). In view of the importance that phosphorylation has been accorded in a multitude of cellular regulatory processes, we have investigated the role of phosphorylation in the control of CD44. In this report we identify the sites of human CD44 phosphorylation by mutating the three conserved cytoplasmic serine residues. We show that both Ser323 and Ser325, but not Ser316, are required for phosphorylation in vivo and demonstrate that this event is not stimulated by phorbol esters. Clonal MDCK cell lines expressing both the single and double CD44 phosphorylation mutants have been generated. These cell lines have been used to directly assess the role of phosphorylation on CD44 localization in polarized epithelial cells and its association with the cytoskeleton."} {"id": "PMID:1281450", "title": "Tight folding of acidic fibroblast growth factor prevents its translocation to the cytosol with diphtheria toxin as vector.", "content": "A fusion protein of acidic fibroblast growth factor and diphtheria toxin A-fragment was disulfide-linked to the toxin B-fragment. The complex bound specifically to diphtheria toxin receptors, and subsequent exposure to low pH induced the fusion protein to translocate to the cytosol. Heparin, inositol hexaphosphate and inorganic sulfate strongly increased the trypsin resistance of the growth factor part of the fusion protein, indicating tight folding, and they prevented translocation of the fusion protein to the cytosol. The data indicate that only a more disordered form of the growth factor is translocation competent.", "contents": "Tight folding of acidic fibroblast growth factor prevents its translocation to the cytosol with diphtheria toxin as vector. A fusion protein of acidic fibroblast growth factor and diphtheria toxin A-fragment was disulfide-linked to the toxin B-fragment. The complex bound specifically to diphtheria toxin receptors, and subsequent exposure to low pH induced the fusion protein to translocate to the cytosol. Heparin, inositol hexaphosphate and inorganic sulfate strongly increased the trypsin resistance of the growth factor part of the fusion protein, indicating tight folding, and they prevented translocation of the fusion protein to the cytosol. The data indicate that only a more disordered form of the growth factor is translocation competent."} {"id": "PMID:1281451", "title": "Muscle-specific expression of SRF-related genes in the early embryo of Xenopus laevis.", "content": "We have isolated two members of the RSRF protein family, SL-1 and SL-2, in Xenopus laevis. Both proteins contain SRF-type DNA binding domains and are related to the human protein, RSRFC4. SL-1 constitutes a novel member of the RSRF family whilst SL-2 is similar to human RSRFC4 throughout its length. SL-1 protein recognizes the consensus DNA sequence CTA(A/T)4TAR in vitro and can bind to the same regulatory sites as other A/T-rich sequence-specific binding activities, such as the muscle-specific regulatory factor, MEF-2. Transcription of both Xenopus genes is restricted to the somitic mesoderm of early embryos and subsequently to the body muscle (myotomes) of the tadpole. In contrast, both genes are expressed ubiquitously in the adult frog. A binding activity, antigenically related to both human RSRFC4 and the SL-2 gene product, is detected in Xenopus embryos and after gastrulation is localized to embryonic muscle. An indistinguishable binding activity is detected in many adult frog tissues. We conclude that the RSRF genes undergo a dramatic switch in their patterns of expression during development. We suggest that RSRF proteins may regulate muscle-specific transcription in embryos, but acquire other roles during the course of development.", "contents": "Muscle-specific expression of SRF-related genes in the early embryo of Xenopus laevis. We have isolated two members of the RSRF protein family, SL-1 and SL-2, in Xenopus laevis. Both proteins contain SRF-type DNA binding domains and are related to the human protein, RSRFC4. SL-1 constitutes a novel member of the RSRF family whilst SL-2 is similar to human RSRFC4 throughout its length. SL-1 protein recognizes the consensus DNA sequence CTA(A/T)4TAR in vitro and can bind to the same regulatory sites as other A/T-rich sequence-specific binding activities, such as the muscle-specific regulatory factor, MEF-2. Transcription of both Xenopus genes is restricted to the somitic mesoderm of early embryos and subsequently to the body muscle (myotomes) of the tadpole. In contrast, both genes are expressed ubiquitously in the adult frog. A binding activity, antigenically related to both human RSRFC4 and the SL-2 gene product, is detected in Xenopus embryos and after gastrulation is localized to embryonic muscle. An indistinguishable binding activity is detected in many adult frog tissues. We conclude that the RSRF genes undergo a dramatic switch in their patterns of expression during development. We suggest that RSRF proteins may regulate muscle-specific transcription in embryos, but acquire other roles during the course of development."} {"id": "PMID:1281452", "title": "In vitro recombination and terminal elongation of RNA by Q beta replicase.", "content": "SV-11 is a short-chain [115 nucleotides (nt)] RNA species that is replicated by Q beta replicase. It is reproducibly selected when MNV-11, another 87 nt RNA species, is extensively amplified by Q beta replicase at high ionic strength and long incubation times. Comparing the sequences of the two species reveals that SV-11 contains an inverse duplication of the high-melting domain of MNV-11. SV-11 is thus a recombinant between the plus and minus strands of MNV-11 resulting in a nearly palindromic sequence. During chain elongation in replication, the chain folds consecutively to a metastable secondary structure of the RNA, which can rearrange spontaneously to a more stable hairpin-form RNA. While the metastable form is an excellent template for Q beta replicase, the stable RNA is unable to serve as template. When initiation of a new chain is suppressed by replacing GTP in the replication mixture by ITP, Q beta replicase adds nucleotides to the 3' terminus of RNA. The replicase uses parts of the RNA sequence, preferentially the 3' terminal part for copying, thereby creating an interior duplication. This reaction is about five orders of magnitude slower than normal template-instructed synthesis. The reaction also adds nucleotides to the 3' terminus of some RNA molecules that are unable to serve as templates for Q beta replicase.", "contents": "In vitro recombination and terminal elongation of RNA by Q beta replicase. SV-11 is a short-chain [115 nucleotides (nt)] RNA species that is replicated by Q beta replicase. It is reproducibly selected when MNV-11, another 87 nt RNA species, is extensively amplified by Q beta replicase at high ionic strength and long incubation times. Comparing the sequences of the two species reveals that SV-11 contains an inverse duplication of the high-melting domain of MNV-11. SV-11 is thus a recombinant between the plus and minus strands of MNV-11 resulting in a nearly palindromic sequence. During chain elongation in replication, the chain folds consecutively to a metastable secondary structure of the RNA, which can rearrange spontaneously to a more stable hairpin-form RNA. While the metastable form is an excellent template for Q beta replicase, the stable RNA is unable to serve as template. When initiation of a new chain is suppressed by replacing GTP in the replication mixture by ITP, Q beta replicase adds nucleotides to the 3' terminus of RNA. The replicase uses parts of the RNA sequence, preferentially the 3' terminal part for copying, thereby creating an interior duplication. This reaction is about five orders of magnitude slower than normal template-instructed synthesis. The reaction also adds nucleotides to the 3' terminus of some RNA molecules that are unable to serve as templates for Q beta replicase."} {"id": "PMID:1281453", "title": "Spontaneous and inducible ventricular arrhythmias in a canine model of chronic heart failure: relation to haemodynamics and sympathoadrenergic activation.", "content": "The relationship between the incidence, frequency and complexity of spontaneous ventricular arrhythmias and the extent of haemodynamic compromise and sympathoadrenergic hyperactivity was evaluated in a canine model of chronic heart failure produced by multiple sequential intracoronary microembolizations. Ambulatory ECG Holter monitoring recorded during chronic heart failure in 18 dogs revealed spontaneous ventricular arrhythmias ranging from single ventricular premature beats (VPBs) to non-sustained episodes of ventricular tachycardia (VT). Single VPBs were present in 94% of dogs, couplets in 67%, triplets in 28% and spontaneous episodes of non-sustained VT in 33%. Dogs with > 28 VPBs.h-1 (n = 9) had a markedly higher plasma norepinephrine (PNE) concentration (1001 +/- 185 vs 561 +/- 31 pg.ml-1) (P < 0.03), and a higher pulmonary artery wedge pressure (PAWP) (18 +/- 2 vs 12 +/- 1 mmHg) (P < 0.03) than dogs with < or = 28 VPBs.h-1 (n = 9). Dogs that developed spontaneous episodes of VT also had significantly higher PNE levels (1119 +/- 247 pg.ml-1) compared to dogs that did not develop VT (612 +/- 64 pg.ml-1) (P < 0.02). Programmed ventricular stimulation performed in seven of 18 dogs resulted in the development of sustained monomorphic VT in three and ventricular fibrillation in three dogs each (43%, 43%). Dogs with inducible sustained monomorphic VT had a significantly higher number of ambient arrhythmias and higher PAWP compared to dogs that did not develop sustained VT. The observed complexity, frequency and incidence of spontaneous and inducible ventricular arrhythmias in this canine model are similar to those described in patients with chronic heart failure.", "contents": "Spontaneous and inducible ventricular arrhythmias in a canine model of chronic heart failure: relation to haemodynamics and sympathoadrenergic activation. The relationship between the incidence, frequency and complexity of spontaneous ventricular arrhythmias and the extent of haemodynamic compromise and sympathoadrenergic hyperactivity was evaluated in a canine model of chronic heart failure produced by multiple sequential intracoronary microembolizations. Ambulatory ECG Holter monitoring recorded during chronic heart failure in 18 dogs revealed spontaneous ventricular arrhythmias ranging from single ventricular premature beats (VPBs) to non-sustained episodes of ventricular tachycardia (VT). Single VPBs were present in 94% of dogs, couplets in 67%, triplets in 28% and spontaneous episodes of non-sustained VT in 33%. Dogs with > 28 VPBs.h-1 (n = 9) had a markedly higher plasma norepinephrine (PNE) concentration (1001 +/- 185 vs 561 +/- 31 pg.ml-1) (P < 0.03), and a higher pulmonary artery wedge pressure (PAWP) (18 +/- 2 vs 12 +/- 1 mmHg) (P < 0.03) than dogs with < or = 28 VPBs.h-1 (n = 9). Dogs that developed spontaneous episodes of VT also had significantly higher PNE levels (1119 +/- 247 pg.ml-1) compared to dogs that did not develop VT (612 +/- 64 pg.ml-1) (P < 0.02). Programmed ventricular stimulation performed in seven of 18 dogs resulted in the development of sustained monomorphic VT in three and ventricular fibrillation in three dogs each (43%, 43%). Dogs with inducible sustained monomorphic VT had a significantly higher number of ambient arrhythmias and higher PAWP compared to dogs that did not develop sustained VT. The observed complexity, frequency and incidence of spontaneous and inducible ventricular arrhythmias in this canine model are similar to those described in patients with chronic heart failure."} {"id": "PMID:1281454", "title": "Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by adherent monocytes measured by quantitative immunoassays.", "content": "The kinetics of GM-CSF and G-CSF secretion by purified adherent human monocytes were studied by quantitative immunoassays. Interleukin-1 (IL-1); 4-40 ng/ml and E. coli lipopolysaccharide (LPS); 0.1-1.00 ng/ml, were the most effective stimuli and induced dose-dependent secretion of both GM-CSF and G-CSF. Secretion of newly synthesized CSF was detectable 3-6 hours after stimulation and continued for approximately 24 h. Twenty minutes pulse exposure to LPS was sufficient to induce half maximum secretion of GM-CSF, and after 24-36 h the adherent monocytes could not be restimulated. Neither GM-CSF nor TNF could down-regulate the secretion of GM-CSF. IL-3 induced a minor secretion of GM-CSF whereas TNF, G-CSF, M-CSF and IFN-gamma were unable to induce GM-CSF secretion. In addition to LPS and IL-1, GM-CSF and to a minor degree TNF induced G-CSF secretion. Enriched T lymphocytes secreted GM-CSF, but not G-CSF, after stimulation with PHA or staphylococcal enterotoxin A (SEA), whereas LPS and IL-1 were without stimulatory effects. We also noted that enriched T lymphocytes added to LPS-stimulated adherent monocytes at ratios of 1:10 or more inhibited, in a dose-dependent fashion, GM-CSF secretion by 13-55%. These findings add new quantitative data on CSF secretion by human monocytes.", "contents": "Granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) secretion by adherent monocytes measured by quantitative immunoassays. The kinetics of GM-CSF and G-CSF secretion by purified adherent human monocytes were studied by quantitative immunoassays. Interleukin-1 (IL-1); 4-40 ng/ml and E. coli lipopolysaccharide (LPS); 0.1-1.00 ng/ml, were the most effective stimuli and induced dose-dependent secretion of both GM-CSF and G-CSF. Secretion of newly synthesized CSF was detectable 3-6 hours after stimulation and continued for approximately 24 h. Twenty minutes pulse exposure to LPS was sufficient to induce half maximum secretion of GM-CSF, and after 24-36 h the adherent monocytes could not be restimulated. Neither GM-CSF nor TNF could down-regulate the secretion of GM-CSF. IL-3 induced a minor secretion of GM-CSF whereas TNF, G-CSF, M-CSF and IFN-gamma were unable to induce GM-CSF secretion. In addition to LPS and IL-1, GM-CSF and to a minor degree TNF induced G-CSF secretion. Enriched T lymphocytes secreted GM-CSF, but not G-CSF, after stimulation with PHA or staphylococcal enterotoxin A (SEA), whereas LPS and IL-1 were without stimulatory effects. We also noted that enriched T lymphocytes added to LPS-stimulated adherent monocytes at ratios of 1:10 or more inhibited, in a dose-dependent fashion, GM-CSF secretion by 13-55%. These findings add new quantitative data on CSF secretion by human monocytes."} {"id": "PMID:1281455", "title": "Phenylarsine oxide augments tyrosine phosphorylation in hematopoietic cells.", "content": "Tyrosine phosphorylation and dephosphorylation are implicated in the regulation of cell growth and differentiation. A diverse identification of key regulatory proteins by their content of phosphotyrosine has been hampered by the very low level of tyrosine phosphorylation. This is presumably caused by the relative preponderance of phosphotyrosine phosphatase activity in many cells. We report that treatment of hematopoietic cells with phenylarsine oxide (PAO), a membrane-permeable phosphotyrosine phosphatase inhibitor, induced a dramatic accumulation of phosphotyrosine in a number of cellular proteins. No changes in serine or threonine phosphorylation were detected. The PAO-induced accumulation of phosphotyrosine occurred well before any signs of toxicity or irreversible damage to the cells were seen. Addition of dithiothreitol reversed the effect of PAO. Our data demonstrate that phosphotyrosine phosphatase activity has a major impact on the level of phosphotyrosine in cellular proteins, even in cells with high protein tyrosine kinase activity. Cells with constitutively elevated tyrosine kinase activity are easily detected following treatment with PAO and substrates with an otherwise too low phosphotyrosine content or too rapid phosphate turnover can be studied. This effect of PAO allows determinations of tyrosine phosphorylation-dependent complex formation between proteins.", "contents": "Phenylarsine oxide augments tyrosine phosphorylation in hematopoietic cells. Tyrosine phosphorylation and dephosphorylation are implicated in the regulation of cell growth and differentiation. A diverse identification of key regulatory proteins by their content of phosphotyrosine has been hampered by the very low level of tyrosine phosphorylation. This is presumably caused by the relative preponderance of phosphotyrosine phosphatase activity in many cells. We report that treatment of hematopoietic cells with phenylarsine oxide (PAO), a membrane-permeable phosphotyrosine phosphatase inhibitor, induced a dramatic accumulation of phosphotyrosine in a number of cellular proteins. No changes in serine or threonine phosphorylation were detected. The PAO-induced accumulation of phosphotyrosine occurred well before any signs of toxicity or irreversible damage to the cells were seen. Addition of dithiothreitol reversed the effect of PAO. Our data demonstrate that phosphotyrosine phosphatase activity has a major impact on the level of phosphotyrosine in cellular proteins, even in cells with high protein tyrosine kinase activity. Cells with constitutively elevated tyrosine kinase activity are easily detected following treatment with PAO and substrates with an otherwise too low phosphotyrosine content or too rapid phosphate turnover can be studied. This effect of PAO allows determinations of tyrosine phosphorylation-dependent complex formation between proteins."} {"id": "PMID:1281456", "title": "Cell-specific expression of cytosolic phosphoenolpyruvate carboxykinase in transgenic mice.", "content": "The gene encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK) is expressed in multiple cell types in diverse tissues including liver, kidney, intestine, and white and brown adipose tissues. It can thus be considered a model system for examining the regulation of cell-specific transcription. The PEPCK gene is transcribed from a single start site, but studies of transgenic mice have revealed that distinct cis-acting elements (and thus different trans-acting factors) regulate PEPCK expression in hepatocytes, renal proximal tubule epithelial cells, and adipocytes. Hepatocytes require elements between -457 and +69 bp; renal proximal tubule epithelia require elements between -363 and +69 bp; and adipocytes require elements between -2086 and -888 bp. An additional element downstream of +69 bp is required to either attenuate PEPCK mRNA levels in liver and fat or increase renal PEPCK mRNA. We hypothesize that the transcription factors C/EBP and DBP are the principal tissue-specific regulators in liver, and that HNF-1 and perhaps C/EBP are important for kidney-specific PEPCK expression. We propose that the putative downstream element is involved in regulating PEPCK mRNA turnover in liver and fat. Finally, we suggest that the fat-specific element is an enhancer that requires a novel adipogenic regulatory factor, ARF6, to function. The long-term objective will be to fine map the cis-acting elements and identify the cognate trans-acting factors that regulate PEPCK in liver, kidney and fat. This information will help elucidate the combinatorial mechanisms that control the cell-specific expression of this complex gene.", "contents": "Cell-specific expression of cytosolic phosphoenolpyruvate carboxykinase in transgenic mice. The gene encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK) is expressed in multiple cell types in diverse tissues including liver, kidney, intestine, and white and brown adipose tissues. It can thus be considered a model system for examining the regulation of cell-specific transcription. The PEPCK gene is transcribed from a single start site, but studies of transgenic mice have revealed that distinct cis-acting elements (and thus different trans-acting factors) regulate PEPCK expression in hepatocytes, renal proximal tubule epithelial cells, and adipocytes. Hepatocytes require elements between -457 and +69 bp; renal proximal tubule epithelia require elements between -363 and +69 bp; and adipocytes require elements between -2086 and -888 bp. An additional element downstream of +69 bp is required to either attenuate PEPCK mRNA levels in liver and fat or increase renal PEPCK mRNA. We hypothesize that the transcription factors C/EBP and DBP are the principal tissue-specific regulators in liver, and that HNF-1 and perhaps C/EBP are important for kidney-specific PEPCK expression. We propose that the putative downstream element is involved in regulating PEPCK mRNA turnover in liver and fat. Finally, we suggest that the fat-specific element is an enhancer that requires a novel adipogenic regulatory factor, ARF6, to function. The long-term objective will be to fine map the cis-acting elements and identify the cognate trans-acting factors that regulate PEPCK in liver, kidney and fat. This information will help elucidate the combinatorial mechanisms that control the cell-specific expression of this complex gene."} {"id": "PMID:1281457", "title": "Alpha 2-macroglobulin, a multifunctional binding protein with targeting characteristics.", "content": "Alpha 2-macroglobulin (alpha 2M) and related proteins share the function of binding host or foreign peptides and particles, thereby serving as humoral defense barriers against pathogens in the plasma and tissues of vertebrates. In human alpha 2M, several reactive sites including high-affinity sites for zinc, transglutaminase cross-linking sites, and reactive sites derived from the activated thiol ester can mediate reversible or irreversible capture of proteins of diverse biological functions. Alpha 2M interacts and captures virtually any proteinase whether self or foreign, suggesting a function as a unique \"panproteinase inhibitor.\" Activation of alpha 2M generates novel binding sites, which mediate complex formation with cytokines and other peptides. Direct evidence of physical association of cytokines with activated alpha 2M indicated its role as biological response modifier in cell cultures. A mechanism commonly referred to as \"clearance of activated alpha 2M\" involves Ca(2+)-dependent binding to a specific cell surface receptor, a member of the low-density lipoprotein receptor supergene family, that mediates cellular uptake by endocytosis and delivery to endosomes and lysosomes. The peptide binding function of alpha 2M, therefore, may also be viewed as a mechanism that allows targeting of biologically active peptides to different cell types expressing the alpha 2M receptor. Internalized complexes may be dispatched into different pathways of endocytic/lysosomal pathways in a cell type-specific manner. In addition, bioactive peptides bound to alpha 2M may dissociate in the process of intracellular ligand sorting, thereby modulating cell function, or remain bound and share the catabolic fate of alpha 2M. The diversified and probably programmed binding functions of alpha 2M indicate that in addition to its role in trapping proteinases, it has other biological activities that remain to be fully defined. That alpha 2M may function as a binding and carrier protein with targeting characteristics is predicted from 1) the known functions of alpha 2M, and 2) the similarity of the fate of alpha 2M with proteins whose significance in targeting and intracellular trafficking has been studied in more detail.", "contents": "Alpha 2-macroglobulin, a multifunctional binding protein with targeting characteristics. Alpha 2-macroglobulin (alpha 2M) and related proteins share the function of binding host or foreign peptides and particles, thereby serving as humoral defense barriers against pathogens in the plasma and tissues of vertebrates. In human alpha 2M, several reactive sites including high-affinity sites for zinc, transglutaminase cross-linking sites, and reactive sites derived from the activated thiol ester can mediate reversible or irreversible capture of proteins of diverse biological functions. Alpha 2M interacts and captures virtually any proteinase whether self or foreign, suggesting a function as a unique \"panproteinase inhibitor.\" Activation of alpha 2M generates novel binding sites, which mediate complex formation with cytokines and other peptides. Direct evidence of physical association of cytokines with activated alpha 2M indicated its role as biological response modifier in cell cultures. A mechanism commonly referred to as \"clearance of activated alpha 2M\" involves Ca(2+)-dependent binding to a specific cell surface receptor, a member of the low-density lipoprotein receptor supergene family, that mediates cellular uptake by endocytosis and delivery to endosomes and lysosomes. The peptide binding function of alpha 2M, therefore, may also be viewed as a mechanism that allows targeting of biologically active peptides to different cell types expressing the alpha 2M receptor. Internalized complexes may be dispatched into different pathways of endocytic/lysosomal pathways in a cell type-specific manner. In addition, bioactive peptides bound to alpha 2M may dissociate in the process of intracellular ligand sorting, thereby modulating cell function, or remain bound and share the catabolic fate of alpha 2M. The diversified and probably programmed binding functions of alpha 2M indicate that in addition to its role in trapping proteinases, it has other biological activities that remain to be fully defined. That alpha 2M may function as a binding and carrier protein with targeting characteristics is predicted from 1) the known functions of alpha 2M, and 2) the similarity of the fate of alpha 2M with proteins whose significance in targeting and intracellular trafficking has been studied in more detail."} {"id": "PMID:1281458", "title": "The Src family of tyrosine protein kinases in hemopoietic signal transduction.", "content": "The Src family of tyrosine protein kinases represent an expanding class of closely related intracellular enzymes that participate in the signal transduction pathways of a variety of surface receptors. One of the more surprising aspects of the information relating Src protein kinases to receptor signaling is the apparent diversity of receptor types with which the Src-related enzymes are reported to interact physically or functionally. Traditional biochemical and genetic approaches have yielded much information regarding the interactions between the Src tyrosine protein kinases and other cellular proteins in defined cell types, and emerging technologies, most notably homologous recombination in embryonal stem cells to achieve gene \"knockouts,\" are providing new insights into the participation of the Src-related gene products in signal transduction and development.", "contents": "The Src family of tyrosine protein kinases in hemopoietic signal transduction. The Src family of tyrosine protein kinases represent an expanding class of closely related intracellular enzymes that participate in the signal transduction pathways of a variety of surface receptors. One of the more surprising aspects of the information relating Src protein kinases to receptor signaling is the apparent diversity of receptor types with which the Src-related enzymes are reported to interact physically or functionally. Traditional biochemical and genetic approaches have yielded much information regarding the interactions between the Src tyrosine protein kinases and other cellular proteins in defined cell types, and emerging technologies, most notably homologous recombination in embryonal stem cells to achieve gene \"knockouts,\" are providing new insights into the participation of the Src-related gene products in signal transduction and development."} {"id": "PMID:1281459", "title": "Anti-tolA antibody in non-A, non-B chronic liver disease.", "content": "We constructed a cDNA library against the plasma obtained from the patient with acute exacerbation of non-A, non-B liver cirrhosis, and immunoscreened this library with the sera obtained from the patients with non-A, non-B chronic liver disease. One positive clone lambda 22C containing about 1.2 kb cDNA insert was isolated from 10(6) clones. Nucleotide sequence determination and subsequent homology search revealed its identity to the tolA gene of Escherichia coli. Anti-tolA antibody was detected in 54.5% of the patients with NANB chronic liver disease whose sera were negative for antibody to hepatitis C virus (anti-C100). In contrast, anti-tolA was detected only of 14.6% patients with anti-C100 positive NANB chronic liver disease, 10.5% with hepatitis B surface antigen-positive chronic liver disease, 7.7% with alcoholic liver disease and 4.2% in normal control, and no positive case in acute hepatitis of etiology and in primary biliary cirrhosis. However, antibody to the core protein of hepatitis C virus (anti-JCC) was detected 50% of the patients whose sera were negative for anti-C100 but positive for anti-tolA. Recently, it has been reported that hepatitis C virus is rich in mutations and has some variants. These results indicated the presence of a common epitope between the tolA protein and some agent related to non-A, non-B hepatitis, especially to anti-C100 negative non-A, non-B hepatitis such as variants of hepatitis C virus which have mutations in C100 coded region.", "contents": "Anti-tolA antibody in non-A, non-B chronic liver disease. We constructed a cDNA library against the plasma obtained from the patient with acute exacerbation of non-A, non-B liver cirrhosis, and immunoscreened this library with the sera obtained from the patients with non-A, non-B chronic liver disease. One positive clone lambda 22C containing about 1.2 kb cDNA insert was isolated from 10(6) clones. Nucleotide sequence determination and subsequent homology search revealed its identity to the tolA gene of Escherichia coli. Anti-tolA antibody was detected in 54.5% of the patients with NANB chronic liver disease whose sera were negative for antibody to hepatitis C virus (anti-C100). In contrast, anti-tolA was detected only of 14.6% patients with anti-C100 positive NANB chronic liver disease, 10.5% with hepatitis B surface antigen-positive chronic liver disease, 7.7% with alcoholic liver disease and 4.2% in normal control, and no positive case in acute hepatitis of etiology and in primary biliary cirrhosis. However, antibody to the core protein of hepatitis C virus (anti-JCC) was detected 50% of the patients whose sera were negative for anti-C100 but positive for anti-tolA. Recently, it has been reported that hepatitis C virus is rich in mutations and has some variants. These results indicated the presence of a common epitope between the tolA protein and some agent related to non-A, non-B hepatitis, especially to anti-C100 negative non-A, non-B hepatitis such as variants of hepatitis C virus which have mutations in C100 coded region."} {"id": "PMID:1281462", "title": "Determination of the origin and nature of brain macrophages and microglial cells in mouse central nervous system, using non-radioactive in situ hybridization and immunoperoxidase techniques.", "content": "The origin and nature of brain macrophages and microglial cells in the mouse central nervous system (CNS) were investigated. First, the expression and localization of determinants recognized by the different monoclonal antibodies (mAbs) MOMA-1, Mac-1-alpha, and F4/80 (raised against cells of the mononuclear phagocyte system) were immunohistochemically studied in the developing and adult mouse brain. In order to clarify the origin of brain macrophages and microglial cells, we used bacteriophage lambda transgenic mice as donors for bone marrow transplantations in recipient mice of different ages. During ontogeny, numerous MOMA-1-, Mac-1-alpha-, and F4/80-positive blood monocyte-derived brain macrophages (amoeboid microglia) infiltrated the CNS parenchyma. These brain macrophages gradually disappeared from the brain parenchyma at postnatal day 7 (P7). From P17 on, Mac-1-alpha- and F4/80-positive cells were detected within the brain parenchyma with the morphology of resting microglial cells. Transitional forms between brain macrophages and \"resting\" microglia were not observed in the developing brain. Combined non-radioactive in situ hybridization and immunohistochemistry revealed many MOMA-1-positive bone marrow-derived brain macrophages that were located in the leptomeninges, the ventricles, and occasionally the blood vessel walls. These results show that brain macrophages are of bone marrow origin. Many \"resting\" microglial cells were detected in the brain, mainly in the white matter. It appeared that about 10% of these cells displayed the transgenic signal. This result indicates that the majority of \"resting\" microglial cells are of local, presumably neuroectodermal, origin.", "contents": "Determination of the origin and nature of brain macrophages and microglial cells in mouse central nervous system, using non-radioactive in situ hybridization and immunoperoxidase techniques. The origin and nature of brain macrophages and microglial cells in the mouse central nervous system (CNS) were investigated. First, the expression and localization of determinants recognized by the different monoclonal antibodies (mAbs) MOMA-1, Mac-1-alpha, and F4/80 (raised against cells of the mononuclear phagocyte system) were immunohistochemically studied in the developing and adult mouse brain. In order to clarify the origin of brain macrophages and microglial cells, we used bacteriophage lambda transgenic mice as donors for bone marrow transplantations in recipient mice of different ages. During ontogeny, numerous MOMA-1-, Mac-1-alpha-, and F4/80-positive blood monocyte-derived brain macrophages (amoeboid microglia) infiltrated the CNS parenchyma. These brain macrophages gradually disappeared from the brain parenchyma at postnatal day 7 (P7). From P17 on, Mac-1-alpha- and F4/80-positive cells were detected within the brain parenchyma with the morphology of resting microglial cells. Transitional forms between brain macrophages and \"resting\" microglia were not observed in the developing brain. Combined non-radioactive in situ hybridization and immunohistochemistry revealed many MOMA-1-positive bone marrow-derived brain macrophages that were located in the leptomeninges, the ventricles, and occasionally the blood vessel walls. These results show that brain macrophages are of bone marrow origin. Many \"resting\" microglial cells were detected in the brain, mainly in the white matter. It appeared that about 10% of these cells displayed the transgenic signal. This result indicates that the majority of \"resting\" microglial cells are of local, presumably neuroectodermal, origin."} {"id": "PMID:1281463", "title": "Cytokeratin expression in corneal endothelium in the iridocorneal endothelial syndrome.", "content": "The immunocytologic characteristics of two formalin-fixed, paraffin-embedded corneas from patients with the iridocorneal endothelial (ICE) syndrome and unaffected control corneas were studied. Binding of polyclonal antisera to Factor VIII, S-100 protein, involucrin, neuron specific enolase (NSE), and the lectins peanut agglutinin and Ulex europaeus agglutinin-1 was performed using the standard peroxidase-anti-peroxidase method. We detected reactive patterns of monoclonal antibodies to cytokeratins (34BE12 is a 56-58 kD mouse IgG reactive to stratified epithelia; Pkk1 is a 44-54 kD mouse IgG reactive to simple epithelia; and KL1 is a 55-57 kD mouse IgG reactive to epidermis and simple epithelia) using the standard avidin-biotin complex method. Staining properties were similar for the polyclonal antisera, lectins, NSE, and chromogranin in corneas with ICE syndrome and in the controls. However, the cytokeratins 34BE12, Pkk1, and KL1 were detected in the endothelium of the corneas with the ICE syndrome but not in the controls. These findings suggest that various cytokeratins are expressed in the corneal endothelium in the ICE syndrome that are not expressed in unaffected corneal endothelium.", "contents": "Cytokeratin expression in corneal endothelium in the iridocorneal endothelial syndrome. The immunocytologic characteristics of two formalin-fixed, paraffin-embedded corneas from patients with the iridocorneal endothelial (ICE) syndrome and unaffected control corneas were studied. Binding of polyclonal antisera to Factor VIII, S-100 protein, involucrin, neuron specific enolase (NSE), and the lectins peanut agglutinin and Ulex europaeus agglutinin-1 was performed using the standard peroxidase-anti-peroxidase method. We detected reactive patterns of monoclonal antibodies to cytokeratins (34BE12 is a 56-58 kD mouse IgG reactive to stratified epithelia; Pkk1 is a 44-54 kD mouse IgG reactive to simple epithelia; and KL1 is a 55-57 kD mouse IgG reactive to epidermis and simple epithelia) using the standard avidin-biotin complex method. Staining properties were similar for the polyclonal antisera, lectins, NSE, and chromogranin in corneas with ICE syndrome and in the controls. However, the cytokeratins 34BE12, Pkk1, and KL1 were detected in the endothelium of the corneas with the ICE syndrome but not in the controls. These findings suggest that various cytokeratins are expressed in the corneal endothelium in the ICE syndrome that are not expressed in unaffected corneal endothelium."} {"id": "PMID:1281464", "title": "[Problems with the intraurethral spiral].", "content": "In the last decade numerous attempts have been undertaken in non-surgical treatment of benign prostatic hyperplasia in order to enable the patient to void his bladder under control, without residual urine and without surgical resection. For the time being, attempts with drug therapy, as well as the more invasive methods with thermic or dilating effect on the prostatogenic infravesical obstruction are based on empiric studies. For many patients transurethral or suprapubic long-term catheterisation is, after all, the only solution. In this respect the \"urologic spiral\" represents a conservative alternative. In 1980 Fabian was the first to report on the successful clinical application of the intraprostatic \"partial catheter\" in 2 patients. 4 years later Fabian's remarkably good results in 48 patients are promising. However, what strikes first as an efficient innovation may also have its shortcomings and complications, as it was our experience in the first applications.", "contents": "[Problems with the intraurethral spiral]. In the last decade numerous attempts have been undertaken in non-surgical treatment of benign prostatic hyperplasia in order to enable the patient to void his bladder under control, without residual urine and without surgical resection. For the time being, attempts with drug therapy, as well as the more invasive methods with thermic or dilating effect on the prostatogenic infravesical obstruction are based on empiric studies. For many patients transurethral or suprapubic long-term catheterisation is, after all, the only solution. In this respect the \"urologic spiral\" represents a conservative alternative. In 1980 Fabian was the first to report on the successful clinical application of the intraprostatic \"partial catheter\" in 2 patients. 4 years later Fabian's remarkably good results in 48 patients are promising. However, what strikes first as an efficient innovation may also have its shortcomings and complications, as it was our experience in the first applications."} {"id": "PMID:1281465", "title": "[Localized hyperthermia of the prostate via the rectum in chronic inoperable urinary retention].", "content": "Local transrectal hyperthermia of the prostate was used to treat 16 poor surgical risk patients who had an indwelling catheter because of chronic urinary retention caused by benign prostatic hypertrophy. We used the Brucker (Prost-care) model with a rectal applicator, a water cooling system and a microwave generator operating at 915 MHz. Intraprostatic temperatures of 42 degrees to 44 degrees C were measured by a radiometric system. 12 patients received a complete treatment which consists in 6 to 10 sessions of one hour and was controlled at least one month later. 8 of them no longer need a catheter. Uroflowmetry was between 7.5 and 17.6 ml/sec and residual urine appreciate by ultrasounds was less than 60 cm3.", "contents": "[Localized hyperthermia of the prostate via the rectum in chronic inoperable urinary retention]. Local transrectal hyperthermia of the prostate was used to treat 16 poor surgical risk patients who had an indwelling catheter because of chronic urinary retention caused by benign prostatic hypertrophy. We used the Brucker (Prost-care) model with a rectal applicator, a water cooling system and a microwave generator operating at 915 MHz. Intraprostatic temperatures of 42 degrees to 44 degrees C were measured by a radiometric system. 12 patients received a complete treatment which consists in 6 to 10 sessions of one hour and was controlled at least one month later. 8 of them no longer need a catheter. Uroflowmetry was between 7.5 and 17.6 ml/sec and residual urine appreciate by ultrasounds was less than 60 cm3."} {"id": "PMID:1281466", "title": "[Infectious complications after transurethral resection].", "content": "300 consecutive TUR were prospectively examined bacteriologically. We used, lacking contraindications, Co-Trimoxazol as antibiotic prophylaxis, when urine at admittance was sterile, otherwise we treated the urinary infection. The antibiotics were applied from the beginning of the intervention until the catheter was removed. Of the 49 patients with a indwelling catheter 28 (57%) had an urinary infection. All but one were cured. 2 of 64 (3%) patients undergoing resection of a bladder tumour acquired asymptomatic nosocomial infection. 198 patients underwent TUR of the prostate with initially sterile urine. 7 patients suffered from fever in the postoperative course, in 6 cases the origin remained unclear. 3 patients showed an asymptomatic nosocomial infection. Overall, with antibiotic prophylaxis we found an infection rate of 2-5% for the TUR of the prostate and of 3% for the TUR of bladder. Primarily infected urine, in this study, did not elevate the risk for infectious complications.", "contents": "[Infectious complications after transurethral resection]. 300 consecutive TUR were prospectively examined bacteriologically. We used, lacking contraindications, Co-Trimoxazol as antibiotic prophylaxis, when urine at admittance was sterile, otherwise we treated the urinary infection. The antibiotics were applied from the beginning of the intervention until the catheter was removed. Of the 49 patients with a indwelling catheter 28 (57%) had an urinary infection. All but one were cured. 2 of 64 (3%) patients undergoing resection of a bladder tumour acquired asymptomatic nosocomial infection. 198 patients underwent TUR of the prostate with initially sterile urine. 7 patients suffered from fever in the postoperative course, in 6 cases the origin remained unclear. 3 patients showed an asymptomatic nosocomial infection. Overall, with antibiotic prophylaxis we found an infection rate of 2-5% for the TUR of the prostate and of 3% for the TUR of bladder. Primarily infected urine, in this study, did not elevate the risk for infectious complications."} {"id": "PMID:1281467", "title": "Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases.", "content": "Mitogen-activated protein (MAP) kinase kinases, intermediates in a growth factor-stimulated protein kinase cascade, are dual specificity protein kinases that specifically phosphorylate and activate MAP kinases in response to extracellular signals. Here, we report the cloning of two forms of cDNA that encode this protein from human T-cells. MKK1a encodes a protein with predicted molecular size of 43,439 Da. Overexpression of this clone in COS cells led to elevated levels of protein and phorbol ester-stimulated MAP kinase kinase activity, confirming that MKK1a encodes the predicted protein. MKK1b, which appears to be an alternatively spliced form of the MKK1a gene, encodes a protein with predicted molecular size of 40,745 Da. Northern analysis revealed that the MKK1 cDNA hybridizes with a single 2.6-kilobase mRNA species in all human tissues examined. Sequence comparison shows homology to a group of yeast kinases that participate in signal transduction and to subdomain XI of other dual specificity kinase.", "contents": "Human T-cell mitogen-activated protein kinase kinases are related to yeast signal transduction kinases. Mitogen-activated protein (MAP) kinase kinases, intermediates in a growth factor-stimulated protein kinase cascade, are dual specificity protein kinases that specifically phosphorylate and activate MAP kinases in response to extracellular signals. Here, we report the cloning of two forms of cDNA that encode this protein from human T-cells. MKK1a encodes a protein with predicted molecular size of 43,439 Da. Overexpression of this clone in COS cells led to elevated levels of protein and phorbol ester-stimulated MAP kinase kinase activity, confirming that MKK1a encodes the predicted protein. MKK1b, which appears to be an alternatively spliced form of the MKK1a gene, encodes a protein with predicted molecular size of 40,745 Da. Northern analysis revealed that the MKK1 cDNA hybridizes with a single 2.6-kilobase mRNA species in all human tissues examined. Sequence comparison shows homology to a group of yeast kinases that participate in signal transduction and to subdomain XI of other dual specificity kinase."} {"id": "PMID:1281468", "title": "A single nucleotide deletion in the skeletal muscle-specific calcium channel transcript of muscular dysgenesis (mdg) mice.", "content": "The skeletal muscle-specific dihydropyridine-sensitive calcium channel is a critical component of excitation-contraction coupling in skeletal muscle. A recessive mutation in mice, muscular dysgenesis (mdg), has previously been described as resulting in defective excitation-contraction coupling. Although the channel-forming subunit (alpha 1) of the skeletal calcium channel is not detectable immunologically, specific mRNA of normal size is present in dysgenic muscle. cDNA for this calcium channel alpha 1 subunit has now been cloned from dysgenic muscle and sequenced in its entirety. A single nucleotide deletion occurs at nucleotide 4010 of the cDNA, resulting in a shift of the translational reading frame. The mutation has been confirmed by direct sequencing of PCR products from homozygous mutant and normal muscle. The mutant polypeptide is predicted to contain the first three repeating domains, five of the normal six transmembrane helices of the last repeating domain, and an altered and truncated C terminus. The mature mRNA encoding the dysgenic alpha 1 subunit appears to be labile. It is possible that premature termination of translation renders the mutant mRNA subject to degradation by nucleases. This work resolves a long-standing controversy on the nature of the primary genetic defect in muscular dysgenesis.", "contents": "A single nucleotide deletion in the skeletal muscle-specific calcium channel transcript of muscular dysgenesis (mdg) mice. The skeletal muscle-specific dihydropyridine-sensitive calcium channel is a critical component of excitation-contraction coupling in skeletal muscle. A recessive mutation in mice, muscular dysgenesis (mdg), has previously been described as resulting in defective excitation-contraction coupling. Although the channel-forming subunit (alpha 1) of the skeletal calcium channel is not detectable immunologically, specific mRNA of normal size is present in dysgenic muscle. cDNA for this calcium channel alpha 1 subunit has now been cloned from dysgenic muscle and sequenced in its entirety. A single nucleotide deletion occurs at nucleotide 4010 of the cDNA, resulting in a shift of the translational reading frame. The mutation has been confirmed by direct sequencing of PCR products from homozygous mutant and normal muscle. The mutant polypeptide is predicted to contain the first three repeating domains, five of the normal six transmembrane helices of the last repeating domain, and an altered and truncated C terminus. The mature mRNA encoding the dysgenic alpha 1 subunit appears to be labile. It is possible that premature termination of translation renders the mutant mRNA subject to degradation by nucleases. This work resolves a long-standing controversy on the nature of the primary genetic defect in muscular dysgenesis."} {"id": "PMID:1281469", "title": "Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor.", "content": "To identify the molecular determinants of ligand-receptor interactions, the extracellular domain of the human neurokinin-1 receptor was systematically substituted with the corresponding sequences from the other two neurokinin receptor subtypes. Three residues within the first extracellular segment and 2 residues of the second segment are required for the optimal binding of all three natural peptide agonists. The divergent nature of 4 of the 5 residues supports the hypothesis that the peptide binding site on the neurokinin-1 receptor is not highly conserved in the other two receptor subtypes. In contrast, substitution of part of the third extracellular segment and the fourth extracellular segment with the corresponding amino acids of the human neurokinin-3 receptor results in an increase in neurokinin B affinity without affecting substance P binding, suggesting that the two peptides do not interact with the same set of functional groups on the receptor. Among the four extracellular regions, only parts of the third and fourth segments affect the binding of the quinuclidine antagonist L-703,606, and these two regions may partially account for the neurokinin-1 receptor subtype specificity of this non-peptide antagonist. These studies demonstrate that both the extracellular and transmembrane domains of the neurokinin-1 receptor are involved in the binding of substance P and related peptides.", "contents": "Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor. To identify the molecular determinants of ligand-receptor interactions, the extracellular domain of the human neurokinin-1 receptor was systematically substituted with the corresponding sequences from the other two neurokinin receptor subtypes. Three residues within the first extracellular segment and 2 residues of the second segment are required for the optimal binding of all three natural peptide agonists. The divergent nature of 4 of the 5 residues supports the hypothesis that the peptide binding site on the neurokinin-1 receptor is not highly conserved in the other two receptor subtypes. In contrast, substitution of part of the third extracellular segment and the fourth extracellular segment with the corresponding amino acids of the human neurokinin-3 receptor results in an increase in neurokinin B affinity without affecting substance P binding, suggesting that the two peptides do not interact with the same set of functional groups on the receptor. Among the four extracellular regions, only parts of the third and fourth segments affect the binding of the quinuclidine antagonist L-703,606, and these two regions may partially account for the neurokinin-1 receptor subtype specificity of this non-peptide antagonist. These studies demonstrate that both the extracellular and transmembrane domains of the neurokinin-1 receptor are involved in the binding of substance P and related peptides."} {"id": "PMID:1281470", "title": "Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580.", "content": "Two non-peptide substance P antagonists exhibit opposite rank orders of potency for the human and rat neurokinin-1 receptors. CP-96,345 shows selectivity for the human receptor, whereas RP67580 shows selectivity for the rat receptor. Amino acid sequence comparison of the two receptors reveals 22 divergent residues. To elucidate the molecular basis for the species selectivity of these antagonists, divergent residues in the human neurokinin-1 receptor were substituted by the rat homologs. Analysis of mutant receptors revealed that substitution of 2 residues (V116L and I290S) in the transmembrane domain of the human neurokinin-1 receptor is both necessary and sufficient to reproduce the antagonist binding affinities of the rat receptor. The nature of these substitutions and the magnitude of the changes in binding affinity suggest that residues 116 and 290 do not interact directly with the antagonist molecules. The present results support a model in which phylogenetically conserved residues interact directly with the antagonists, while phylogenetically divergent residues affect the local helical packing of the receptor. Such a change in local structure would lead to increased binding affinity for one class of antagonists and decreased affinity for another.", "contents": "Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580. Two non-peptide substance P antagonists exhibit opposite rank orders of potency for the human and rat neurokinin-1 receptors. CP-96,345 shows selectivity for the human receptor, whereas RP67580 shows selectivity for the rat receptor. Amino acid sequence comparison of the two receptors reveals 22 divergent residues. To elucidate the molecular basis for the species selectivity of these antagonists, divergent residues in the human neurokinin-1 receptor were substituted by the rat homologs. Analysis of mutant receptors revealed that substitution of 2 residues (V116L and I290S) in the transmembrane domain of the human neurokinin-1 receptor is both necessary and sufficient to reproduce the antagonist binding affinities of the rat receptor. The nature of these substitutions and the magnitude of the changes in binding affinity suggest that residues 116 and 290 do not interact directly with the antagonist molecules. The present results support a model in which phylogenetically conserved residues interact directly with the antagonists, while phylogenetically divergent residues affect the local helical packing of the receptor. Such a change in local structure would lead to increased binding affinity for one class of antagonists and decreased affinity for another."} {"id": "PMID:1281471", "title": "Tetrahydrobiopterin synthesis. An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle.", "content": "Nitric oxide (NO) synthesis is induced in vascular smooth muscle cells by lipopolysaccharide (LPS) where it appears to mediate a variety of vascular dysfunctions. In some cell types tetrahydrobiopterin (BH4) synthesis has also been found to be induced by cytokines. Because BH4 is a cofactor for NO synthase, we investigated whether BH4 synthesis is required for LPS-induced NO production in rat aortic smooth muscle cells (RASMC). The total biopterin content (BH4 and more oxidized states) of untreated RASMC was below our limit of detection. However, treatment with LPS caused a significant rise in biopterin levels and an induction of NO synthesis; both effects of LPS were markedly potentiated by interferon-gamma. 2,4-Diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of GTP cyclohydrolase I, the rate-limiting enzyme for de novo BH4 synthesis, completely abolished the elevated biopterin levels induced by LPS. DAHP also caused a concentration-dependent inhibition of LPS-induced NO synthesis. Inhibition of NO synthesis by DAHP was reversed by sepiapterin, an agent which circumvents the inhibition of biopterin synthesis by DAHP by serving as a substrate for BH4 synthesis via the pterin salvage pathway. The reversal by sepiapterin was overcome by methotrexate, an inhibitor of the pterin salvage pathway. Sepiapterin, and to a lesser extent BH4, dose-dependently enhanced LPS-induced NO synthesis, indicating that BH4 concentration limits the rate of NO production by LPS-activated RASMC. Sepiapterin also caused LPS-induced NO synthesis to appear with an abbreviated lag period phase, suggesting that BH4 availability also limits the onset of NO synthesis. In contrast to the stimulation of LPS-induced NO synthesis, observed when sepiapterin was given alone, sepiapterin became a potent inhibitor of NO synthesis in the presence of methotrexate. This is attributable to a direct inhibitory action of sepiapterin on GTP cyclohydrolase I, an activity which is only revealed after blocking the metabolism of sepiapterin to BH4. Further studies with sepiapterin, methotrexate, and N-acetylserotonin (an inhibitor of the BH4 synthetic enzyme, sepiapterin reductase) indicated that the BH4 is synthesized in RASMC predominantly from GTP; however, a lesser amount may derive from pterin salvage. We demonstrate that BH4 synthesis is an absolute requirement for induction of NO synthesis by LPS in vascular smooth muscle. Our findings also suggest that pterin synthesis inhibitors may be useful for the therapy of endotoxin- and cytokine-induced shock.", "contents": "Tetrahydrobiopterin synthesis. An absolute requirement for cytokine-induced nitric oxide generation by vascular smooth muscle. Nitric oxide (NO) synthesis is induced in vascular smooth muscle cells by lipopolysaccharide (LPS) where it appears to mediate a variety of vascular dysfunctions. In some cell types tetrahydrobiopterin (BH4) synthesis has also been found to be induced by cytokines. Because BH4 is a cofactor for NO synthase, we investigated whether BH4 synthesis is required for LPS-induced NO production in rat aortic smooth muscle cells (RASMC). The total biopterin content (BH4 and more oxidized states) of untreated RASMC was below our limit of detection. However, treatment with LPS caused a significant rise in biopterin levels and an induction of NO synthesis; both effects of LPS were markedly potentiated by interferon-gamma. 2,4-Diamino-6-hydroxypyrimidine (DAHP), a selective inhibitor of GTP cyclohydrolase I, the rate-limiting enzyme for de novo BH4 synthesis, completely abolished the elevated biopterin levels induced by LPS. DAHP also caused a concentration-dependent inhibition of LPS-induced NO synthesis. Inhibition of NO synthesis by DAHP was reversed by sepiapterin, an agent which circumvents the inhibition of biopterin synthesis by DAHP by serving as a substrate for BH4 synthesis via the pterin salvage pathway. The reversal by sepiapterin was overcome by methotrexate, an inhibitor of the pterin salvage pathway. Sepiapterin, and to a lesser extent BH4, dose-dependently enhanced LPS-induced NO synthesis, indicating that BH4 concentration limits the rate of NO production by LPS-activated RASMC. Sepiapterin also caused LPS-induced NO synthesis to appear with an abbreviated lag period phase, suggesting that BH4 availability also limits the onset of NO synthesis. In contrast to the stimulation of LPS-induced NO synthesis, observed when sepiapterin was given alone, sepiapterin became a potent inhibitor of NO synthesis in the presence of methotrexate. This is attributable to a direct inhibitory action of sepiapterin on GTP cyclohydrolase I, an activity which is only revealed after blocking the metabolism of sepiapterin to BH4. Further studies with sepiapterin, methotrexate, and N-acetylserotonin (an inhibitor of the BH4 synthetic enzyme, sepiapterin reductase) indicated that the BH4 is synthesized in RASMC predominantly from GTP; however, a lesser amount may derive from pterin salvage. We demonstrate that BH4 synthesis is an absolute requirement for induction of NO synthesis by LPS in vascular smooth muscle. Our findings also suggest that pterin synthesis inhibitors may be useful for the therapy of endotoxin- and cytokine-induced shock."} {"id": "PMID:1281472", "title": "Rabbit skeletal muscle glycogenin. Molecular cloning and production of fully functional protein in Escherichia coli.", "content": "Glycogenin is a self-glucosylating protein involved in the initiation reactions of glycogen synthesis. Initiation occurs in two stages, requiring first the covalent attachment of a glucose residue to Tyr-194 of glycogenin and then elongation to form an oligosaccharide chain. The latter reaction is known to be catalyzed by glycogenin itself. The glycogenin sequence determined from the protein by Campbell and Cohen (Campbell, D. G., and Cohen, P. (1989) Eur. J. Biochem. 185, 119-125) was used to design oligonucleotide probes to screen a rabbit muscle lambda gt11 library. A cDNA was isolated that predicted an amino acid sequence identical to that of Campbell and Cohen, except that Cys residues replaced Ser-88 and Leu-97. Northern analysis indicated a strongly hybridizing message of 1.8 kilobases, present in most tissues including skeletal muscle, but much weaker in kidney and scarcely detectable in liver. A much weaker 3-kilobase message was also detected in muscle. Polymerase chain reaction was used to isolate DNA fragments encoding a portion of glycogenin from rat and cow. The sequence of this segment was > 90% identical at the amino acid level across the three species, indicating that glycogenin is a highly conserved protein. Using the pET-8c vector, the glycogenin protein was expressed in Escherichia coli. Incubation of the recombinant glycogenin with UDP-[14C]glucose and Mn2+ resulted in labeling of the glycogenin protein, indicating that the recombinant glycogenin was enzymatically active and capable of self-glucosylation. Furthermore, after incubation with UDP-glucose, the recombinant glycogenin could serve as a substrate for glycogen synthase, leading to the production of high M(r) polysaccharide. Therefore, production of functional glycogenin did not require the intervention of any other mammalian protein.", "contents": "Rabbit skeletal muscle glycogenin. Molecular cloning and production of fully functional protein in Escherichia coli. Glycogenin is a self-glucosylating protein involved in the initiation reactions of glycogen synthesis. Initiation occurs in two stages, requiring first the covalent attachment of a glucose residue to Tyr-194 of glycogenin and then elongation to form an oligosaccharide chain. The latter reaction is known to be catalyzed by glycogenin itself. The glycogenin sequence determined from the protein by Campbell and Cohen (Campbell, D. G., and Cohen, P. (1989) Eur. J. Biochem. 185, 119-125) was used to design oligonucleotide probes to screen a rabbit muscle lambda gt11 library. A cDNA was isolated that predicted an amino acid sequence identical to that of Campbell and Cohen, except that Cys residues replaced Ser-88 and Leu-97. Northern analysis indicated a strongly hybridizing message of 1.8 kilobases, present in most tissues including skeletal muscle, but much weaker in kidney and scarcely detectable in liver. A much weaker 3-kilobase message was also detected in muscle. Polymerase chain reaction was used to isolate DNA fragments encoding a portion of glycogenin from rat and cow. The sequence of this segment was > 90% identical at the amino acid level across the three species, indicating that glycogenin is a highly conserved protein. Using the pET-8c vector, the glycogenin protein was expressed in Escherichia coli. Incubation of the recombinant glycogenin with UDP-[14C]glucose and Mn2+ resulted in labeling of the glycogenin protein, indicating that the recombinant glycogenin was enzymatically active and capable of self-glucosylation. Furthermore, after incubation with UDP-glucose, the recombinant glycogenin could serve as a substrate for glycogen synthase, leading to the production of high M(r) polysaccharide. Therefore, production of functional glycogenin did not require the intervention of any other mammalian protein."} {"id": "PMID:1281473", "title": "The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase.", "content": "Lipoprotein lipase (LPL), the major lipolytic enzyme involved in the conversion of triglyceride-rich lipoproteins to remnants, was found to compete with binding of activated alpha 2-macroglobulin (alpha 2M*) to the low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor. Bovine milk LPL displaced both 125I-labeled alpha 2M* and 39-kDa alpha 2M receptor-associated protein (RAP) from the surface of cultured mutant fibroblasts lacking LDL receptors with apparent KI values at 4 degrees C of 6.8 and 30 nM, respectively. Furthermore, LPL inhibited the cellular degradation of 125I-alpha 2M* at 37 degrees C. Because both alpha 2M* and RAP interact with LRP, these data suggest that LPL binds specifically to this receptor. This was further supported by observing that an immunoaffinity-isolated polyclonal antibody against LRP blocked cellular degradation of 125I-LPL in a dose-dependent manner. In addition, 125I-LPL bound to highly purified LRP in a solid-phase assay with a KD of 18 nM, and this binding could be partially displaced with alpha 2M* (KI = 7 nM) and RAP (KI = 3 nM). Taken together, these data establish that LPL binds with high affinity to LRP and undergoes LRP-mediated cellular uptake. The implication of these findings for lipoprotein catabolism in vivo may be important if LRP binding is preserved when LPL is attached to lipoproteins. If so, LPL might facilitate LRP-mediated clearance of lipoproteins.", "contents": "The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase. Lipoprotein lipase (LPL), the major lipolytic enzyme involved in the conversion of triglyceride-rich lipoproteins to remnants, was found to compete with binding of activated alpha 2-macroglobulin (alpha 2M*) to the low density lipoprotein receptor-related protein (LRP)/alpha 2-macroglobulin receptor. Bovine milk LPL displaced both 125I-labeled alpha 2M* and 39-kDa alpha 2M receptor-associated protein (RAP) from the surface of cultured mutant fibroblasts lacking LDL receptors with apparent KI values at 4 degrees C of 6.8 and 30 nM, respectively. Furthermore, LPL inhibited the cellular degradation of 125I-alpha 2M* at 37 degrees C. Because both alpha 2M* and RAP interact with LRP, these data suggest that LPL binds specifically to this receptor. This was further supported by observing that an immunoaffinity-isolated polyclonal antibody against LRP blocked cellular degradation of 125I-LPL in a dose-dependent manner. In addition, 125I-LPL bound to highly purified LRP in a solid-phase assay with a KD of 18 nM, and this binding could be partially displaced with alpha 2M* (KI = 7 nM) and RAP (KI = 3 nM). Taken together, these data establish that LPL binds with high affinity to LRP and undergoes LRP-mediated cellular uptake. The implication of these findings for lipoprotein catabolism in vivo may be important if LRP binding is preserved when LPL is attached to lipoproteins. If so, LPL might facilitate LRP-mediated clearance of lipoproteins."} {"id": "PMID:1281474", "title": "Construction of a chimeric ArsA-ArsB protein for overexpression of the oxyanion-translocating ATPase.", "content": "Resistance to toxic oxyanions of arsenic and antimony in Escherichia coli is conferred by the conjugative R-factor R773, which encodes an ATP-driven anion extrusion pump. The ars operon is composed of three structural genes, arsA, arsB, and arsC. Although transcribed as a single unit, the three genes are differentially expressed as a result of translational differences, such that the ArsA and ArsC proteins are produced in high amounts relative to the amount of ArsB protein made. Consequently, biochemical characterization of the ArsB protein, which is an integral membrane protein containing the anion-conducting pathway, has been limited, precluding studies of the mechanism of this oxyanion pump. To overexpress the arsB gene, a series of changes were made. First, the second codon, an infrequently used leucine codon, was changed to a more frequently utilized codon. Second, a GC-rich stem-loop (delta G = -17 kcal/mol) between the third and twelfth codons was destabilized by changing several of the bases of the base-paired region. Third, the re-engineered arsB gene was fused 3' in frame to the first 1458 base pairs of the arsA gene to encode a 914-residue chimeric protein (486 residues of the ArsA protein plus 428 residues of the mutated ArsB protein) containing the entire re-engineered ArsB sequence except for the initiating methionine. The ArsA-ArsB chimera has been overexpressed at approximately 15-20% of the total membrane proteins. Cells producing the chimeric ArsA-ArsB protein with an arsA gene in trans excluded 73AsO2- from cells, demonstrating that the chimera can function as a component of the oxyanion-translocating ATPase.", "contents": "Construction of a chimeric ArsA-ArsB protein for overexpression of the oxyanion-translocating ATPase. Resistance to toxic oxyanions of arsenic and antimony in Escherichia coli is conferred by the conjugative R-factor R773, which encodes an ATP-driven anion extrusion pump. The ars operon is composed of three structural genes, arsA, arsB, and arsC. Although transcribed as a single unit, the three genes are differentially expressed as a result of translational differences, such that the ArsA and ArsC proteins are produced in high amounts relative to the amount of ArsB protein made. Consequently, biochemical characterization of the ArsB protein, which is an integral membrane protein containing the anion-conducting pathway, has been limited, precluding studies of the mechanism of this oxyanion pump. To overexpress the arsB gene, a series of changes were made. First, the second codon, an infrequently used leucine codon, was changed to a more frequently utilized codon. Second, a GC-rich stem-loop (delta G = -17 kcal/mol) between the third and twelfth codons was destabilized by changing several of the bases of the base-paired region. Third, the re-engineered arsB gene was fused 3' in frame to the first 1458 base pairs of the arsA gene to encode a 914-residue chimeric protein (486 residues of the ArsA protein plus 428 residues of the mutated ArsB protein) containing the entire re-engineered ArsB sequence except for the initiating methionine. The ArsA-ArsB chimera has been overexpressed at approximately 15-20% of the total membrane proteins. Cells producing the chimeric ArsA-ArsB protein with an arsA gene in trans excluded 73AsO2- from cells, demonstrating that the chimera can function as a component of the oxyanion-translocating ATPase."} {"id": "PMID:1281475", "title": "Investigation of the lectin-like binding domains in pertussis toxin using synthetic peptide sequences. Identification of a sialic acid binding site in the S2 subunit of the toxin.", "content": "Synthetic peptides corresponding to selected sequences in the S2 and S3 subunits of pertussis toxin were prepared and evaluated for their ability to inhibit the binding of biotinylated pertussis toxin and three biotinylated sialic acid specific plant lectins to fetuin and asialofetuin. The screening results indicated that two regions in the S2 subunit corresponding to amino acids 78-98 and 123-154 inhibited pertussis toxin binding to fetuin at submillimolar concentrations, while S3 sequences corresponding to amino acids 87-108 and 134-154 inhibited pertussis toxin-biotin binding to asialofetuin albeit with lower affinity. These results confirm earlier findings, which suggest that the S2 subunit is responsible for binding sialylated glycoconjugates. This was further confirmed by the ability of S2 peptides to inhibit the binding of the lectins from Maackia amurensis and wheat germ to fetuin. Two additional peptides from the S2 subunit of pertussis toxin corresponding to sequences 9-23 and 1-23 were found to contain within their sequences a 6-amino acid fragment which has strong homology with a sequence in wheat germ agglutinin that has been shown to be a component of the sialic acid binding site as determined by x-ray crystallography. One of these sequences from S2 (9-23) was biotinylated and evaluated for its ability to bind to carbohydrate. Through a series of experiments using fetuin, asialofetuin, asialoagalactofetuin, and simple saccharides, the biotinylated peptide was shown to bind with high affinity to sialic acid-containing glycoconjugates indicating that these sequences within the S2 subunit of pertussis toxin also play an important role in binding sialic acid.", "contents": "Investigation of the lectin-like binding domains in pertussis toxin using synthetic peptide sequences. Identification of a sialic acid binding site in the S2 subunit of the toxin. Synthetic peptides corresponding to selected sequences in the S2 and S3 subunits of pertussis toxin were prepared and evaluated for their ability to inhibit the binding of biotinylated pertussis toxin and three biotinylated sialic acid specific plant lectins to fetuin and asialofetuin. The screening results indicated that two regions in the S2 subunit corresponding to amino acids 78-98 and 123-154 inhibited pertussis toxin binding to fetuin at submillimolar concentrations, while S3 sequences corresponding to amino acids 87-108 and 134-154 inhibited pertussis toxin-biotin binding to asialofetuin albeit with lower affinity. These results confirm earlier findings, which suggest that the S2 subunit is responsible for binding sialylated glycoconjugates. This was further confirmed by the ability of S2 peptides to inhibit the binding of the lectins from Maackia amurensis and wheat germ to fetuin. Two additional peptides from the S2 subunit of pertussis toxin corresponding to sequences 9-23 and 1-23 were found to contain within their sequences a 6-amino acid fragment which has strong homology with a sequence in wheat germ agglutinin that has been shown to be a component of the sialic acid binding site as determined by x-ray crystallography. One of these sequences from S2 (9-23) was biotinylated and evaluated for its ability to bind to carbohydrate. Through a series of experiments using fetuin, asialofetuin, asialoagalactofetuin, and simple saccharides, the biotinylated peptide was shown to bind with high affinity to sialic acid-containing glycoconjugates indicating that these sequences within the S2 subunit of pertussis toxin also play an important role in binding sialic acid."} {"id": "PMID:1281476", "title": "Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo.", "content": "We have utilized antisense oligodeoxynucleotides (ODNs) to modulate transcriptional activation by the human T-cell leukemia virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo. Terminal substitution did not affect the affinity of ODNs for their target sequence but conferred a 9-fold increase in tax inhibition in vitro. When delivered into mice by intraperitoneal injection, ODNs inhibited tax expression in established tumors by 90%. Unmanipulated tax-transformed mouse fibroblasts, or HTLV-I-transformed human lymphocytes, showed at least 5-fold higher ODN binding and uptake over control cells. Balb/3T3 cell binding was induced to similar levels by cellular activators. This suggests that constitutive activation by tax transformation may increase susceptibility of HTLV-I-transformed cells to antisense therapy, providing a rationale for the use of antisense ODN therapeutics in HTLV-I-associated diseases.", "contents": "Human T-cell leukemia virus type I tax transformation is associated with increased uptake of oligodeoxynucleotides in vitro and in vivo. We have utilized antisense oligodeoxynucleotides (ODNs) to modulate transcriptional activation by the human T-cell leukemia virus type I (HTLV-I) tax gene, the major transcriptional regulator of this virus. 3'-Terminal phosphorothioate-modified antisense ODNs were shown to efficiently inhibit Tax protein expression both in vitro and in vivo. Terminal substitution did not affect the affinity of ODNs for their target sequence but conferred a 9-fold increase in tax inhibition in vitro. When delivered into mice by intraperitoneal injection, ODNs inhibited tax expression in established tumors by 90%. Unmanipulated tax-transformed mouse fibroblasts, or HTLV-I-transformed human lymphocytes, showed at least 5-fold higher ODN binding and uptake over control cells. Balb/3T3 cell binding was induced to similar levels by cellular activators. This suggests that constitutive activation by tax transformation may increase susceptibility of HTLV-I-transformed cells to antisense therapy, providing a rationale for the use of antisense ODN therapeutics in HTLV-I-associated diseases."} {"id": "PMID:1281477", "title": "Interferon-induced Mx proteins form oligomers and contain a putative leucine zipper.", "content": "Interferons induce a number of different proteins that mediate the antiproliferative, antiviral, and immunomodulatory functions of interferons. At least three different proteins mediate the antiviral response, and one of them, Mx protein, specifically inhibits the replication of influenza virus and (vesicular stomatitis virus). Mouse and rat Mx1 proteins are nuclear, whereas other presently known Mx proteins are cytoplasmic. The cellular functions of Mx proteins are unknown, but all of them contain a consensus GTP binding site. Very little information is available on the structure and characteristics of the mouse Mx1 protein itself. For biochemical characterization, we expressed mouse Mx1 protein in a baculovirus system and purified it to homogeneity. The purified protein as well as the authentic murine cellular Mx1 protein exists in dimers and trimers in the presence of dissociating solvents, whereas in physiological buffers they form aggregates. Cross-linking experiments done on Mx-expressing cells from various species revealed that mouse, rat, and human Mx proteins exist predominantly in trimers. Amino acid sequence analysis shows that all known Mx proteins have conserved leucine repeats typical for a leucine zipper at their COOH-terminal end. In vitro translation of chimeric catechol O-methyltransferase-Mx1 gene constructs revealed that the leucine zipper domain of Mx1 protein is responsible for the oligomerization. The COOH terminus also functions as a nuclear localization signal. Microinjection of purified oligomers into the cell cytoplasm resulted in a fast accumulation of the protein in the resulted in a fast accumulation of the protein in the nucleus. Immunoelectron microscopy revealed that nuclear murine Mx1 protein exists in distinct, electron-dense structures separate from nuclear membrane, and chromatin, or nucleolus. These observations reveal that a COOH-terminal leucine zipper domain is an important structural element of all Mx proteins. Its relevance to the biology and functions of Mx proteins is presently not known.", "contents": "Interferon-induced Mx proteins form oligomers and contain a putative leucine zipper. Interferons induce a number of different proteins that mediate the antiproliferative, antiviral, and immunomodulatory functions of interferons. At least three different proteins mediate the antiviral response, and one of them, Mx protein, specifically inhibits the replication of influenza virus and (vesicular stomatitis virus). Mouse and rat Mx1 proteins are nuclear, whereas other presently known Mx proteins are cytoplasmic. The cellular functions of Mx proteins are unknown, but all of them contain a consensus GTP binding site. Very little information is available on the structure and characteristics of the mouse Mx1 protein itself. For biochemical characterization, we expressed mouse Mx1 protein in a baculovirus system and purified it to homogeneity. The purified protein as well as the authentic murine cellular Mx1 protein exists in dimers and trimers in the presence of dissociating solvents, whereas in physiological buffers they form aggregates. Cross-linking experiments done on Mx-expressing cells from various species revealed that mouse, rat, and human Mx proteins exist predominantly in trimers. Amino acid sequence analysis shows that all known Mx proteins have conserved leucine repeats typical for a leucine zipper at their COOH-terminal end. In vitro translation of chimeric catechol O-methyltransferase-Mx1 gene constructs revealed that the leucine zipper domain of Mx1 protein is responsible for the oligomerization. The COOH terminus also functions as a nuclear localization signal. Microinjection of purified oligomers into the cell cytoplasm resulted in a fast accumulation of the protein in the resulted in a fast accumulation of the protein in the nucleus. Immunoelectron microscopy revealed that nuclear murine Mx1 protein exists in distinct, electron-dense structures separate from nuclear membrane, and chromatin, or nucleolus. These observations reveal that a COOH-terminal leucine zipper domain is an important structural element of all Mx proteins. Its relevance to the biology and functions of Mx proteins is presently not known."} {"id": "PMID:1281478", "title": "Tumor necrosis factor stimulates multiple serine/threonine protein kinases in Swiss 3T3 and L929 cells. Implication of casein kinase-2 and extracellular signal-regulated kinases in the tumor necrosis factor signal transduction pathway.", "content": "Incubation of Swiss 3T3 or L929 cells with tumor necrosis factor (TNF) leads to the rapid stimulation of several cytosolic Ser/Thr kinases active toward myelin basic protein, the S6 peptide (RRLSSLR), the G peptide (SPQPSRRGSESSEE), and Kemptide (LRRASLG). This confirms the hypothesis that kinases other than protein kinases A and C may be involved in the TNF signal transduction. Chromatography on Mono Q resolved multiple kinase peaks with each substrate tested and moreover revealed a TNF-mediated casein kinase-2 activation in both cell lines, measurable with the specific RRREEESEEE peptide or with the G peptide. The TNF-stimulated myelin basic protein kinases-1 and -2 were identified as extracellular signal-regulated kinases-2 and -1, respectively, based on their elution pattern on Mono Q chromatography, their inactivation by protein phosphatase action, their reaction with phosphothreonine and phosphotyrosine antibodies, and by their migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as 42- and 44-kDa proteins recognized by anti-extracellular signal-regulated kinase antibodies.", "contents": "Tumor necrosis factor stimulates multiple serine/threonine protein kinases in Swiss 3T3 and L929 cells. Implication of casein kinase-2 and extracellular signal-regulated kinases in the tumor necrosis factor signal transduction pathway. Incubation of Swiss 3T3 or L929 cells with tumor necrosis factor (TNF) leads to the rapid stimulation of several cytosolic Ser/Thr kinases active toward myelin basic protein, the S6 peptide (RRLSSLR), the G peptide (SPQPSRRGSESSEE), and Kemptide (LRRASLG). This confirms the hypothesis that kinases other than protein kinases A and C may be involved in the TNF signal transduction. Chromatography on Mono Q resolved multiple kinase peaks with each substrate tested and moreover revealed a TNF-mediated casein kinase-2 activation in both cell lines, measurable with the specific RRREEESEEE peptide or with the G peptide. The TNF-stimulated myelin basic protein kinases-1 and -2 were identified as extracellular signal-regulated kinases-2 and -1, respectively, based on their elution pattern on Mono Q chromatography, their inactivation by protein phosphatase action, their reaction with phosphothreonine and phosphotyrosine antibodies, and by their migration on sodium dodecyl sulfate-polyacrylamide gel electrophoresis as 42- and 44-kDa proteins recognized by anti-extracellular signal-regulated kinase antibodies."} {"id": "PMID:1281479", "title": "Mechanism and fidelity of HIV reverse transcriptase.", "content": "We have examined the RNA-dependent and DNA-dependent polymerase and ribonuclease H catalytic activities of human immunodeficiency virus reverse transcriptase using rapid transient kinetic methods with defined synthetic 25/45-mer DNA/RNA and DNA/DNA primer/templates. The Kd value for interaction of the enzyme with duplex DNA was 4.7 nM, and the value for RNA/DNA heteroduplex was of similar magnitude. A pre-steady state burst of nucleoside triphosphate incorporation was observed for both DNA and RNA templates. Analysis of the dATP concentration dependence of the burst rate provided Kd values for dATP of 4 and 14 microM and maximum rates of single nucleotide incorporation, kpol, of 33 and 74 s-1, for DNA and RNA templates, respectively. Subsequent turnovers were limited by the rate of dissociation of the primer/template from the enzyme at rates of 0.18 and 0.06 s-1 for duplex DNA and RNA/DNA heteroduplex, respectively. Analysis of rates of DNA polymerization and RNA cleavage using the RNA template revealed that the two activities are independent of one another. The polymerization rate (4-70 s-1) was dependent on dATP concentration, whereas the RNA cleavage occurred at a constant rate of 10 s-1 over the 100-fold dATP concentration range (2-200 microM). Examination of the RNA cleavage products resulting from a single turnover indicates that the polymerase and ribonuclease domains of the enzyme are separated by a distance corresponding to 19 bases of RNA/DNA heteroduplex, consistent with the recently published crystal structure (Kohlstaedt, L. A., Wang, J., Friedman, J., Rice, P. A., and Steitz, T. A. (1992) Science 256, 1783-1790). Analysis of the kinetics of processive synthesis suggested that the initial binding of dNTP leads to a faster rate of dissociation of DNA from the enzyme. Further investigation supported a two-step dNTP binding mechanism with the formation of an initial E.DNA.dNTP complex followed by a more stable E'.DNA.dNTP complex. The Kd values for incorporation of incorrect nucleoside triphosphates opposite a DNA template thymidine were 1010 microM for dGTP, 1240 microM for dCTP, and 840 microM for dTTP. The corresponding maximum kpol rates were 4.8 s-1 for dGTP, 0.52 s-1 for dCTP, and 0.41 s-1 for dTTP. These values provide fidelity estimates of 1740 for discrimination against dGTP, 19,700 for dCTP, and 16,900 for dTTP misincorporations at this site.", "contents": "Mechanism and fidelity of HIV reverse transcriptase. We have examined the RNA-dependent and DNA-dependent polymerase and ribonuclease H catalytic activities of human immunodeficiency virus reverse transcriptase using rapid transient kinetic methods with defined synthetic 25/45-mer DNA/RNA and DNA/DNA primer/templates. The Kd value for interaction of the enzyme with duplex DNA was 4.7 nM, and the value for RNA/DNA heteroduplex was of similar magnitude. A pre-steady state burst of nucleoside triphosphate incorporation was observed for both DNA and RNA templates. Analysis of the dATP concentration dependence of the burst rate provided Kd values for dATP of 4 and 14 microM and maximum rates of single nucleotide incorporation, kpol, of 33 and 74 s-1, for DNA and RNA templates, respectively. Subsequent turnovers were limited by the rate of dissociation of the primer/template from the enzyme at rates of 0.18 and 0.06 s-1 for duplex DNA and RNA/DNA heteroduplex, respectively. Analysis of rates of DNA polymerization and RNA cleavage using the RNA template revealed that the two activities are independent of one another. The polymerization rate (4-70 s-1) was dependent on dATP concentration, whereas the RNA cleavage occurred at a constant rate of 10 s-1 over the 100-fold dATP concentration range (2-200 microM). Examination of the RNA cleavage products resulting from a single turnover indicates that the polymerase and ribonuclease domains of the enzyme are separated by a distance corresponding to 19 bases of RNA/DNA heteroduplex, consistent with the recently published crystal structure (Kohlstaedt, L. A., Wang, J., Friedman, J., Rice, P. A., and Steitz, T. A. (1992) Science 256, 1783-1790). Analysis of the kinetics of processive synthesis suggested that the initial binding of dNTP leads to a faster rate of dissociation of DNA from the enzyme. Further investigation supported a two-step dNTP binding mechanism with the formation of an initial E.DNA.dNTP complex followed by a more stable E'.DNA.dNTP complex. The Kd values for incorporation of incorrect nucleoside triphosphates opposite a DNA template thymidine were 1010 microM for dGTP, 1240 microM for dCTP, and 840 microM for dTTP. The corresponding maximum kpol rates were 4.8 s-1 for dGTP, 0.52 s-1 for dCTP, and 0.41 s-1 for dTTP. These values provide fidelity estimates of 1740 for discrimination against dGTP, 19,700 for dCTP, and 16,900 for dTTP misincorporations at this site."} {"id": "PMID:1281480", "title": "Cross-talk between tyrosine kinase and G-protein-linked receptors. Phosphorylation of beta 2-adrenergic receptors in response to insulin.", "content": "Protein kinases play a pivotal role in the propagation and modulation of transmembrane signaling pathways. Two major classes of receptors, G-protein-linked and tyrosine kinase receptors not only propagate signals but also are substrates for phosphorylation in response to stimulation by agonist ligands. Insulin (operating via tyrosine kinase receptors) and catecholamines (operating by G-protein-linked receptors) are counterregulatory with respect to lipid and carbohydrate metabolism. How, on a cellular level, these two distinct classes of receptors may cross-regulate each other remains controversial. In the present work we identify a novel cross-talk between members of two distinct classes of receptors, tyrosine kinase (insulin) and G-protein-linked (beta-adrenergic) receptors. Treatment of DDT1 MF-2 hamster vas deferens smooth muscle cells with insulin promoted a marked attenuation (desensitization) of beta-adrenergic receptor-mediated activation of adenylylcyclase. Measured by immune precipitation of beta 2-adrenergic receptors from cells metabolically labeled with [32P]orthophosphate, the basal state of receptor phosphorylation was increased 2-fold by insulin. Phosphoamino acid analysis revealed that for insulin-stimulated cells, the beta 2-adrenergic receptors showed increased phosphorylation on tyrosyl and decreased phosphorylation on threonyl residues. Phosphorylation of the beta-adrenergic receptor was rapid and peaked at 30 min following stimulation of cells by insulin. beta-Adrenergic receptor phosphorylation and attenuation of catecholamine-sensitive adenylylcyclase provide a biochemical basis for the counterregulatory effects of insulin upon catecholamine action.", "contents": "Cross-talk between tyrosine kinase and G-protein-linked receptors. Phosphorylation of beta 2-adrenergic receptors in response to insulin. Protein kinases play a pivotal role in the propagation and modulation of transmembrane signaling pathways. Two major classes of receptors, G-protein-linked and tyrosine kinase receptors not only propagate signals but also are substrates for phosphorylation in response to stimulation by agonist ligands. Insulin (operating via tyrosine kinase receptors) and catecholamines (operating by G-protein-linked receptors) are counterregulatory with respect to lipid and carbohydrate metabolism. How, on a cellular level, these two distinct classes of receptors may cross-regulate each other remains controversial. In the present work we identify a novel cross-talk between members of two distinct classes of receptors, tyrosine kinase (insulin) and G-protein-linked (beta-adrenergic) receptors. Treatment of DDT1 MF-2 hamster vas deferens smooth muscle cells with insulin promoted a marked attenuation (desensitization) of beta-adrenergic receptor-mediated activation of adenylylcyclase. Measured by immune precipitation of beta 2-adrenergic receptors from cells metabolically labeled with [32P]orthophosphate, the basal state of receptor phosphorylation was increased 2-fold by insulin. Phosphoamino acid analysis revealed that for insulin-stimulated cells, the beta 2-adrenergic receptors showed increased phosphorylation on tyrosyl and decreased phosphorylation on threonyl residues. Phosphorylation of the beta-adrenergic receptor was rapid and peaked at 30 min following stimulation of cells by insulin. beta-Adrenergic receptor phosphorylation and attenuation of catecholamine-sensitive adenylylcyclase provide a biochemical basis for the counterregulatory effects of insulin upon catecholamine action."} {"id": "PMID:1281481", "title": "Sequence analysis, tissue distribution, and expression of rat cathepsin S.", "content": "Cysteine proteases are involved in many diverse cellular processes ranging from processing of precursor proteins to intracellular degradation. In an effort to identify novel cysteine proteases, we used the polymerase chain reaction and primers directed against the catalytic sites of previously cloned cysteine proteases. From rat brain mRNA, a 600-base pair band was amplified; cloning and partial sequence analysis of this band resulted in the identification of cathepsins B and L and five novel sequences. The novel cDNAs contained a number of residues conserved in lysosomal cysteine proteases, including the active site residue His159 (papain numbering). In addition, the amino acid homology between the novel sequences and either cathepsins B, L, or H, ranged from 63 to 32%. The insert with highest homology was used to screen a rat brain cDNA library; a 1334-base pair cDNA was isolated and the nucleotide sequence determined. This sequence encodes an open reading frame of 330 amino acids which is 82% homologous to human cathepsin S, suggesting that this sequence represents rat cathepsin S. Northern blot analysis for rat cathepsin S revealed tissue-specific expression distinct from the distribution of cathepsin B and L. The regulation of expression of rat cathepsin S mRNA in response to thyroid-stimulating hormone was studied in a rat thyroid cell line FRTL-5. The level of cathepsin S mRNA was substantially increased in response to thyroid-stimulating hormone, whereas cathepsin B and cathepsin L mRNA levels were not altered by this treatment. A portion of cDNA encoding the predicted mature protein of rat cathepsin S was expressed as a glutathione S-transferase-fusion protein. The affinity-purified protein exhibited proteolytic activity with properties similar to bovine cathepsin S. Taken together, these results imply highly specific functions for cathepsin S.", "contents": "Sequence analysis, tissue distribution, and expression of rat cathepsin S. Cysteine proteases are involved in many diverse cellular processes ranging from processing of precursor proteins to intracellular degradation. In an effort to identify novel cysteine proteases, we used the polymerase chain reaction and primers directed against the catalytic sites of previously cloned cysteine proteases. From rat brain mRNA, a 600-base pair band was amplified; cloning and partial sequence analysis of this band resulted in the identification of cathepsins B and L and five novel sequences. The novel cDNAs contained a number of residues conserved in lysosomal cysteine proteases, including the active site residue His159 (papain numbering). In addition, the amino acid homology between the novel sequences and either cathepsins B, L, or H, ranged from 63 to 32%. The insert with highest homology was used to screen a rat brain cDNA library; a 1334-base pair cDNA was isolated and the nucleotide sequence determined. This sequence encodes an open reading frame of 330 amino acids which is 82% homologous to human cathepsin S, suggesting that this sequence represents rat cathepsin S. Northern blot analysis for rat cathepsin S revealed tissue-specific expression distinct from the distribution of cathepsin B and L. The regulation of expression of rat cathepsin S mRNA in response to thyroid-stimulating hormone was studied in a rat thyroid cell line FRTL-5. The level of cathepsin S mRNA was substantially increased in response to thyroid-stimulating hormone, whereas cathepsin B and cathepsin L mRNA levels were not altered by this treatment. A portion of cDNA encoding the predicted mature protein of rat cathepsin S was expressed as a glutathione S-transferase-fusion protein. The affinity-purified protein exhibited proteolytic activity with properties similar to bovine cathepsin S. Taken together, these results imply highly specific functions for cathepsin S."} {"id": "PMID:1281482", "title": "The cyclic peptide synthetase catalyzing HC-toxin production in the filamentous fungus Cochliobolus carbonum is encoded by a 15.7-kilobase open reading frame.", "content": "Race 1 of Cochliobolus carbonum, a fungal plant pathogen, owes its exceptional virulence on certain genotypes of maize to the production of HC-toxin, a cyclic tetrapeptide. Production of HC-toxin is controlled by a single known gene, TOX2. Race 1, but not races that do not make HC-toxin, contains two copies of a 22-kilobase (kb) region of chromosomal DNA that is required for HC-toxin biosynthesis and hence virulence. We have sequenced this 22-kb region and here show that it contains an open reading frame of 15.7 kb that encodes a multifunctional cyclic peptide synthetase of potential M(r)574,620. This gene, called HTS1, apparently contains no introns. The predicted gene product, HC-toxin synthetase (HTS), contains four amino acid-binding (adenylate-forming) domains that are highly similar to those found in other cyclic peptide synthetases and other adenylate-binding enzymes. The DNA sequence encodes tryptic peptides derived from two HC-toxin biosynthetic enzymes, HC-toxin synthetase 1 (HTS-1) and HC-toxin synthetase 2 (HTS-2), indicating that these two enzymes exist in vivo as part of a single polypeptide. Consistent with this, in some enzyme preparations antibodies against the enzyme HTS-2, which was originally purified as a protein with a subunit M(r) of 160,000, recognize a protein with an estimated subunit M(r) greater than 480,000.", "contents": "The cyclic peptide synthetase catalyzing HC-toxin production in the filamentous fungus Cochliobolus carbonum is encoded by a 15.7-kilobase open reading frame. Race 1 of Cochliobolus carbonum, a fungal plant pathogen, owes its exceptional virulence on certain genotypes of maize to the production of HC-toxin, a cyclic tetrapeptide. Production of HC-toxin is controlled by a single known gene, TOX2. Race 1, but not races that do not make HC-toxin, contains two copies of a 22-kilobase (kb) region of chromosomal DNA that is required for HC-toxin biosynthesis and hence virulence. We have sequenced this 22-kb region and here show that it contains an open reading frame of 15.7 kb that encodes a multifunctional cyclic peptide synthetase of potential M(r)574,620. This gene, called HTS1, apparently contains no introns. The predicted gene product, HC-toxin synthetase (HTS), contains four amino acid-binding (adenylate-forming) domains that are highly similar to those found in other cyclic peptide synthetases and other adenylate-binding enzymes. The DNA sequence encodes tryptic peptides derived from two HC-toxin biosynthetic enzymes, HC-toxin synthetase 1 (HTS-1) and HC-toxin synthetase 2 (HTS-2), indicating that these two enzymes exist in vivo as part of a single polypeptide. Consistent with this, in some enzyme preparations antibodies against the enzyme HTS-2, which was originally purified as a protein with a subunit M(r) of 160,000, recognize a protein with an estimated subunit M(r) greater than 480,000."} {"id": "PMID:1281483", "title": "Tumor necrosis factor-alpha down-regulates human elastin gene expression. Evidence for the role of AP-1 in the suppression of promoter activity.", "content": "Cytokine modulation of elastin gene expression was examined by assay of elastin mRNA abundance and by transient transfections of cultured human skin fibroblasts and rat aortic smooth muscle cells with elastin promoter/reporter gene (chloramphenicol acetyltransferase, CAT) constructs. Incubation of cells with human recombinant tumor necrosis factor-alpha (TNF-alpha) markedly suppressed the elastin mRNA levels in a time- and dose-dependent manner by up to 91%. TNF-alpha also suppressed the expression of the elastin promoter/CAT construct by up to 70% in transiently transfected cells, indicating regulation at the transcriptional level. This suppression was temporally preceded by rapid and transient up-regulation of c-jun and c-fos genes. The down-regulatory effect of TNF-alpha on elastin promoter activity was abolished by co-transfections with a synthetic double-stranded AP-1 oligomer. Furthermore, co-transfection of the elastin promoter construct with c-jun and c-fos expression plasmids resulted in a marked decrease in the promoter activity. Elucidation of the cis-regulatory elements in the elastin promoter by 5' deletion construct analysis implicated a region -290 to -198 containing one AP-1 binding site. The functional role of this AP-1 site was further tested by gel retardation assays which indicated formation of a DNA-protein complex specific for TNF-alpha treated cells. This complex could be partially dissociated by a competing oligomer containing the consensus AP-1 binding site. These observations suggest that the inhibitory effects of TNF-alpha on elastin gene expression involve the transcription factor AP-1. Interferon-gamma also suppressed the elastin gene expression at the mRNA level by approximately 52%, but it had no effect on the elastin promoter activity, suggesting post-transcriptional mechanisms. These results indicate that mediators released from inflammatory cells can modulate elastin gene expression, and such modulation may play a role in diseases characterized by altered accumulation of elastic fibers in tissues.", "contents": "Tumor necrosis factor-alpha down-regulates human elastin gene expression. Evidence for the role of AP-1 in the suppression of promoter activity. Cytokine modulation of elastin gene expression was examined by assay of elastin mRNA abundance and by transient transfections of cultured human skin fibroblasts and rat aortic smooth muscle cells with elastin promoter/reporter gene (chloramphenicol acetyltransferase, CAT) constructs. Incubation of cells with human recombinant tumor necrosis factor-alpha (TNF-alpha) markedly suppressed the elastin mRNA levels in a time- and dose-dependent manner by up to 91%. TNF-alpha also suppressed the expression of the elastin promoter/CAT construct by up to 70% in transiently transfected cells, indicating regulation at the transcriptional level. This suppression was temporally preceded by rapid and transient up-regulation of c-jun and c-fos genes. The down-regulatory effect of TNF-alpha on elastin promoter activity was abolished by co-transfections with a synthetic double-stranded AP-1 oligomer. Furthermore, co-transfection of the elastin promoter construct with c-jun and c-fos expression plasmids resulted in a marked decrease in the promoter activity. Elucidation of the cis-regulatory elements in the elastin promoter by 5' deletion construct analysis implicated a region -290 to -198 containing one AP-1 binding site. The functional role of this AP-1 site was further tested by gel retardation assays which indicated formation of a DNA-protein complex specific for TNF-alpha treated cells. This complex could be partially dissociated by a competing oligomer containing the consensus AP-1 binding site. These observations suggest that the inhibitory effects of TNF-alpha on elastin gene expression involve the transcription factor AP-1. Interferon-gamma also suppressed the elastin gene expression at the mRNA level by approximately 52%, but it had no effect on the elastin promoter activity, suggesting post-transcriptional mechanisms. These results indicate that mediators released from inflammatory cells can modulate elastin gene expression, and such modulation may play a role in diseases characterized by altered accumulation of elastic fibers in tissues."} {"id": "PMID:1281484", "title": "Partial purification of the cystic fibrosis transmembrane conductance regulator.", "content": "We have investigated several purification strategies for the cystic fibrosis transmembrane regulator (CFTR) based on its structural similarity to other proteins of the traffic ATPase/ABC transporter family. Recombinant CFTR expressed in heterologous cells was readily solubilized by digitonin and initially separated from the majority of other cellular proteins by sucrose density gradient centrifugation. CFTR, with two predicted nucleotide binding domains, bound avidly to several triazine dye columns, although elution with MgATP, MgCl2, or high ionic strength buffers was inefficient. CFTR did not bind to either ATP or ADP coupled to agarose. Because CFTR is a glycoprotein we investigated its binding to lectin columns. CFTR bound readily to wheat germ agglutinin, but poorly to Lens culinaris agglutinin. CFTR was enriched 9-10 times when eluted from wheat germ agglutinin with N-acetylglucosamine. This enrichment was tripled if lectin chromatography followed sucrose gradient centrifugation. Our results suggest the combination of sucrose density gradient centrifugation and lectin chromatography would be a satisfactory approach to initial purification of CFTR expressed in heterologous cells.", "contents": "Partial purification of the cystic fibrosis transmembrane conductance regulator. We have investigated several purification strategies for the cystic fibrosis transmembrane regulator (CFTR) based on its structural similarity to other proteins of the traffic ATPase/ABC transporter family. Recombinant CFTR expressed in heterologous cells was readily solubilized by digitonin and initially separated from the majority of other cellular proteins by sucrose density gradient centrifugation. CFTR, with two predicted nucleotide binding domains, bound avidly to several triazine dye columns, although elution with MgATP, MgCl2, or high ionic strength buffers was inefficient. CFTR did not bind to either ATP or ADP coupled to agarose. Because CFTR is a glycoprotein we investigated its binding to lectin columns. CFTR bound readily to wheat germ agglutinin, but poorly to Lens culinaris agglutinin. CFTR was enriched 9-10 times when eluted from wheat germ agglutinin with N-acetylglucosamine. This enrichment was tripled if lectin chromatography followed sucrose gradient centrifugation. Our results suggest the combination of sucrose density gradient centrifugation and lectin chromatography would be a satisfactory approach to initial purification of CFTR expressed in heterologous cells."} {"id": "PMID:1281485", "title": "Octreotide stimulates insulin-like growth factor-binding protein-1: a potential pituitary-independent mechanism for drug action.", "content": "As the long-acting somatostatin analog octreotide attenuates polypeptide hormone hypersecretion, it has recently been used to effectively treat acromegaly and gastrointestinal carcinoid tumors. Most growth-promoting actions of GH are mediated by insulin-like growth factor-I (IGF-I), which circulates complexed with multiple binding proteins (IGFBPs). IGFBP-1, a nonglycosylated peptide, competes with the IGF-I receptor for ligand binding and also regulates IGF action. To examine GH-independent mechanisms for octreotide regulation of the GH axis, circulating levels of IGFBP-1 were measured hourly after sc octreotide or saline administration in normal and GH-deficient adults. As IGFBP-1 is inhibited by insulin and GH, the dynamic pattern of alterations in GH and insulin levels was also assessed. After octreotide (100 micrograms) administration to 10 normal subjects, mean IGFBP-1 concentrations were stimulated from 23 +/- 4 to 72 +/- 18 micrograms/L (P < 0.007 vs. saline) after 2 h. Maximal induction of IGFBP-1 levels occurred after 3 h (325 +/- 115 micrograms/L; P < 0.02 vs. saline) and remained elevated (P < 0.005) for 6 h. IGFBP-1 was induced by octreotide in all subjects and was confirmed by Western ligand blotting. Insulin and GH levels preceding the rise in IGFBP-1 were unaltered by octreotide. Octreotide stimulated IGFBP-1 5-fold during a sustained fast in 4 normal subjects, despite equally suppressed insulin levels in both saline- and octreotide-treated groups. In 4 GH-deficient adults, IGFBP-1 levels were stimulated by octreotide from 16 +/- 3 to 146 +/- 36 and 154 +/- 28 micrograms/L after 3 and 4 h, respectively. In conclusion, the somatostatin analog octreotide induces IGFBP-1 independently of GH and insulin. As IGFBP-1 regulates the action of IGF-I, octreotide stimulation of IGFBPs may represent an additional pharmacological mechanism for attenuating the GH-IGF-I axis.", "contents": "Octreotide stimulates insulin-like growth factor-binding protein-1: a potential pituitary-independent mechanism for drug action. As the long-acting somatostatin analog octreotide attenuates polypeptide hormone hypersecretion, it has recently been used to effectively treat acromegaly and gastrointestinal carcinoid tumors. Most growth-promoting actions of GH are mediated by insulin-like growth factor-I (IGF-I), which circulates complexed with multiple binding proteins (IGFBPs). IGFBP-1, a nonglycosylated peptide, competes with the IGF-I receptor for ligand binding and also regulates IGF action. To examine GH-independent mechanisms for octreotide regulation of the GH axis, circulating levels of IGFBP-1 were measured hourly after sc octreotide or saline administration in normal and GH-deficient adults. As IGFBP-1 is inhibited by insulin and GH, the dynamic pattern of alterations in GH and insulin levels was also assessed. After octreotide (100 micrograms) administration to 10 normal subjects, mean IGFBP-1 concentrations were stimulated from 23 +/- 4 to 72 +/- 18 micrograms/L (P < 0.007 vs. saline) after 2 h. Maximal induction of IGFBP-1 levels occurred after 3 h (325 +/- 115 micrograms/L; P < 0.02 vs. saline) and remained elevated (P < 0.005) for 6 h. IGFBP-1 was induced by octreotide in all subjects and was confirmed by Western ligand blotting. Insulin and GH levels preceding the rise in IGFBP-1 were unaltered by octreotide. Octreotide stimulated IGFBP-1 5-fold during a sustained fast in 4 normal subjects, despite equally suppressed insulin levels in both saline- and octreotide-treated groups. In 4 GH-deficient adults, IGFBP-1 levels were stimulated by octreotide from 16 +/- 3 to 146 +/- 36 and 154 +/- 28 micrograms/L after 3 and 4 h, respectively. In conclusion, the somatostatin analog octreotide induces IGFBP-1 independently of GH and insulin. As IGFBP-1 regulates the action of IGF-I, octreotide stimulation of IGFBPs may represent an additional pharmacological mechanism for attenuating the GH-IGF-I axis."} {"id": "PMID:1281486", "title": "Immunohistochemical studies on the intrinsic pancreatic nerves in the chicken.", "content": "A peroxidase anti-peroxidase method or an avidin-biotinylated complex method was used to visualize neural elements immunostained for several neuropeptides in the chicken pancreas. Pancreatic ganglion cells were only immunoreactive with vasoactive intestinal polypeptide (VIP), galanin and substance P (SP) antisera. VIP-immunoreactive (IR) ganglion cells were the most numerous, and most of them also showed the distinct immunoreaction with galanin. VIP- and galanin-IR nerve fibers were observed in the exocrine portion, the adventitia of the artery and the connective tissue of the ductal wall. The number and distribution of the VIP- and galanin-IR nerve fibers around the artery and duct were similar. SP-IR nerve fibers were found mainly close to the blood vessel. SP- and CGRP-IR nerve fibers were detected in the VIP-IR ganglion and extrapancreatic nerve bundle. Tyrosine hydroxylase (TH)- and aromatic L-amino acid decarboxylase (AADC)-IR nerve fibers were observed as nerve bundles in the interlobular space or extrapancreatic nerves. Consequently, VIP and galanin coexist in the intrinsic neural elements. SP is partially located in the intrinsic neural elements, but most of it seems likely to originate from the extrinsic ganglion. It is probable that calcitonin gene related peptide (CGRP)-, TH- and AADC-IR nerve fibers have an extrinsic origin.", "contents": "Immunohistochemical studies on the intrinsic pancreatic nerves in the chicken. A peroxidase anti-peroxidase method or an avidin-biotinylated complex method was used to visualize neural elements immunostained for several neuropeptides in the chicken pancreas. Pancreatic ganglion cells were only immunoreactive with vasoactive intestinal polypeptide (VIP), galanin and substance P (SP) antisera. VIP-immunoreactive (IR) ganglion cells were the most numerous, and most of them also showed the distinct immunoreaction with galanin. VIP- and galanin-IR nerve fibers were observed in the exocrine portion, the adventitia of the artery and the connective tissue of the ductal wall. The number and distribution of the VIP- and galanin-IR nerve fibers around the artery and duct were similar. SP-IR nerve fibers were found mainly close to the blood vessel. SP- and CGRP-IR nerve fibers were detected in the VIP-IR ganglion and extrapancreatic nerve bundle. Tyrosine hydroxylase (TH)- and aromatic L-amino acid decarboxylase (AADC)-IR nerve fibers were observed as nerve bundles in the interlobular space or extrapancreatic nerves. Consequently, VIP and galanin coexist in the intrinsic neural elements. SP is partially located in the intrinsic neural elements, but most of it seems likely to originate from the extrinsic ganglion. It is probable that calcitonin gene related peptide (CGRP)-, TH- and AADC-IR nerve fibers have an extrinsic origin."} {"id": "PMID:1281487", "title": "Galanin stimulates phosphatidylinositol turnover in cardiac tissue of the mudpuppy.", "content": "A galanin-like peptide has been found in the parasympathetic fibers innervating the mudpuppy myocardium and direct application of galanin produces hyperpolarization of atrial myocytes and a decrease in twitch tension. In the present study, atrial and ventricular strips were incubated with galanin and then evaluated for changes in either phosphatidylinositol turnover or cyclic nucleotide levels. Galanin caused a significant and concentration-dependent increase in phosphatidylinositol turnover in both atrial and ventricular tissue. However, galanin had no effect on cyclic AMP or cyclic GMP levels in either basal or adrenergically-stimulated preparations. These results suggest that the galanin-induced cardio-inhibition in the mudpuppy may be mediated, at least in part, by a change in phosphatidylinositol turnover.", "contents": "Galanin stimulates phosphatidylinositol turnover in cardiac tissue of the mudpuppy. A galanin-like peptide has been found in the parasympathetic fibers innervating the mudpuppy myocardium and direct application of galanin produces hyperpolarization of atrial myocytes and a decrease in twitch tension. In the present study, atrial and ventricular strips were incubated with galanin and then evaluated for changes in either phosphatidylinositol turnover or cyclic nucleotide levels. Galanin caused a significant and concentration-dependent increase in phosphatidylinositol turnover in both atrial and ventricular tissue. However, galanin had no effect on cyclic AMP or cyclic GMP levels in either basal or adrenergically-stimulated preparations. These results suggest that the galanin-induced cardio-inhibition in the mudpuppy may be mediated, at least in part, by a change in phosphatidylinositol turnover."} {"id": "PMID:1281488", "title": "Transforming growth factor-beta is the major mediator of natural suppressor cells derived from normal bone marrow.", "content": "We previously reported that murine bone marrow cells activated by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) had potent nonspecific natural suppressor (NS) cell activity. In the present study, we demonstrated that these activated NS cells released a soluble factor (or factors) capable of nonspecifically inhibiting T cell mitogenic responses. Consistent with the properties of transforming growth factor-beta (TGF-beta), treatment of the NS supernates with heat failed to denature the factor, and in fact significantly increased its suppressive activity. The NS suppressor factor strongly inhibited proliferation of the TGF-beta-sensitive tumor cell line, A549. Cytokine activation of suppressive activity correlated with the production of a 10- to 13-kDa protein, consistent with the size of TGF-beta and rIL-3 induced a sevenfold increase in TGF-beta transcription. Finally, neutralizing anti-TGF-beta antibody inhibited the suppressive activity of the supernates, indicating that TGF-beta was responsible for most, if not all, of the suppression expressed by these bone marrow NS cells.", "contents": "Transforming growth factor-beta is the major mediator of natural suppressor cells derived from normal bone marrow. We previously reported that murine bone marrow cells activated by interleukin-3 (IL-3) or granulocyte-macrophage colony-stimulating factor (GM-CSF) had potent nonspecific natural suppressor (NS) cell activity. In the present study, we demonstrated that these activated NS cells released a soluble factor (or factors) capable of nonspecifically inhibiting T cell mitogenic responses. Consistent with the properties of transforming growth factor-beta (TGF-beta), treatment of the NS supernates with heat failed to denature the factor, and in fact significantly increased its suppressive activity. The NS suppressor factor strongly inhibited proliferation of the TGF-beta-sensitive tumor cell line, A549. Cytokine activation of suppressive activity correlated with the production of a 10- to 13-kDa protein, consistent with the size of TGF-beta and rIL-3 induced a sevenfold increase in TGF-beta transcription. Finally, neutralizing anti-TGF-beta antibody inhibited the suppressive activity of the supernates, indicating that TGF-beta was responsible for most, if not all, of the suppression expressed by these bone marrow NS cells."} {"id": "PMID:1281489", "title": "Expression of the DAF (CD55) and CD59 antigens during normal hematopoietic cell differentiation.", "content": "Expression of decay-accelerating factor (DAF or CD55) and of CD59 during hematopoietic cell development in normal bone marrow and on peripheral blood leukocytes were characterized by three-color immunofluorescence experiments. With this technique cell subsets were identified by forward light scatter, orthogonal light scatter, and two cell-surface antigens. For each cell lineage, specific combinations of two monoclonal antibodies labeled with different fluorochromes were used. DAF or CD59 were then quantitated on the defined cell subsets from the fluorescence signal of the respective antibody conjugated with a third fluorochrome. Early uncommitted hematopoietic progenitor cells (CD34+, CD38-) all expressed both proteins homogeneously. Initial commitment to the erythroid (CD71+, CD45dim), myeloid (CD33+), or B lymphocyte (CD10+) lineages was not associated with changes in DAF or CD59 levels. With erythroid development, i.e., after loss of CD45 and decrease of CD71, expression of both proteins decreased. With myeloid maturation, expression of CD59 remained constant and expression of DAF varied. During neutrophil maturation, DAF decreased initially and then reemerged on maturing neutrophils concurrently with the appearance of CD16 (Fc gamma RIII), whereas during monocyte maturation, DAF increased concurrently with up-regulation of CD14. With B cell development, expression of DAF increased concurrently with down-regulation of CD10 and up-regulation of CD20, whereas expression of CD59 diminished slightly late in B cell maturation. Analysis of peripheral blood elements showed that monocytes, neutrophils, and B lymphocytes expressed both proteins homogeneously, but that in contrast to other cell subsets, which all expressed CD59, only a subset of (CD3+) T lymphocytes and (CD16+) Natural killer cells expressed DAF. The absence of DAF was not related to CD4 or CD8 expression or to the presence of activation markers (CD25+, CD38+), memory cell markers (CD58+, CD45RO+), or virgin T cell markers (CD45RA+), but was correlated with expression of CD11b (CR3) and CD11c (gp150/95). Although CD21+ (CR2) and CD35+ (CR1) cells all expressed DAF, CD11a (LFA-1) levels correlated inversely with those of DAF. Although the presence of CD55 and CD59 on early progenitor cells and throughout hematopoietic cell development is consistent with the requirements for both proteins in protection of host cells from complement-mediated injury, the physiological relevance of the unique patterns of variation for each cell lineage is unclear. Nevertheless, the availability of a detailed DAF and CD59 expression map in normal marrow will facilitate analyses of alterations during hematopoietic development that may occur in hematological disorders including paroxysmal nocturnal hemoglobinuria (PNH).", "contents": "Expression of the DAF (CD55) and CD59 antigens during normal hematopoietic cell differentiation. Expression of decay-accelerating factor (DAF or CD55) and of CD59 during hematopoietic cell development in normal bone marrow and on peripheral blood leukocytes were characterized by three-color immunofluorescence experiments. With this technique cell subsets were identified by forward light scatter, orthogonal light scatter, and two cell-surface antigens. For each cell lineage, specific combinations of two monoclonal antibodies labeled with different fluorochromes were used. DAF or CD59 were then quantitated on the defined cell subsets from the fluorescence signal of the respective antibody conjugated with a third fluorochrome. Early uncommitted hematopoietic progenitor cells (CD34+, CD38-) all expressed both proteins homogeneously. Initial commitment to the erythroid (CD71+, CD45dim), myeloid (CD33+), or B lymphocyte (CD10+) lineages was not associated with changes in DAF or CD59 levels. With erythroid development, i.e., after loss of CD45 and decrease of CD71, expression of both proteins decreased. With myeloid maturation, expression of CD59 remained constant and expression of DAF varied. During neutrophil maturation, DAF decreased initially and then reemerged on maturing neutrophils concurrently with the appearance of CD16 (Fc gamma RIII), whereas during monocyte maturation, DAF increased concurrently with up-regulation of CD14. With B cell development, expression of DAF increased concurrently with down-regulation of CD10 and up-regulation of CD20, whereas expression of CD59 diminished slightly late in B cell maturation. Analysis of peripheral blood elements showed that monocytes, neutrophils, and B lymphocytes expressed both proteins homogeneously, but that in contrast to other cell subsets, which all expressed CD59, only a subset of (CD3+) T lymphocytes and (CD16+) Natural killer cells expressed DAF. The absence of DAF was not related to CD4 or CD8 expression or to the presence of activation markers (CD25+, CD38+), memory cell markers (CD58+, CD45RO+), or virgin T cell markers (CD45RA+), but was correlated with expression of CD11b (CR3) and CD11c (gp150/95). Although CD21+ (CR2) and CD35+ (CR1) cells all expressed DAF, CD11a (LFA-1) levels correlated inversely with those of DAF. Although the presence of CD55 and CD59 on early progenitor cells and throughout hematopoietic cell development is consistent with the requirements for both proteins in protection of host cells from complement-mediated injury, the physiological relevance of the unique patterns of variation for each cell lineage is unclear. Nevertheless, the availability of a detailed DAF and CD59 expression map in normal marrow will facilitate analyses of alterations during hematopoietic development that may occur in hematological disorders including paroxysmal nocturnal hemoglobinuria (PNH)."} {"id": "PMID:1281490", "title": "The 25 kDa synaptosomal-associated protein SNAP-25 is the major methionine-rich polypeptide in rapid axonal transport and a major substrate for palmitoylation in adult CNS.", "content": "A conspicuous correlate of the developmental transformation of axonal growth cones to synaptic terminals is a marked increase in synthesis and axonal transport of a methionine-rich, acidic polypeptide of approximately 25 kDa. This polypeptide, designated \"super protein\" (SuP), is the most prominent species among methionine-labeled proteins conveyed by rapid axonal transport in mature CNS and PNS neurons of warm- and cold-blooded vertebrates. We show here that SuP is identical to SNAP-25, a highly conserved synaptic protein of known primary structure, by immunoprecipitation with anti-SNAP-25 antiserum of SuP labeled with 35S-methionine and transported by retinal ganglion cells of rat and cat. In addition, we show that SNAP-25/SuP is the most prominent species among retinal polypeptides that incorporate 3H-palmitate in vivo, that it is fatty acylated through a hydroxylamine-labile, thioester bond, and that palmitoylated SNAP-25/SuP is axonally transported. Thus, SNAP-25/SuP is a rapidly transported constituent of the presynaptic apparatus and a major neuronal substrate for long-chain fatty acylation.", "contents": "The 25 kDa synaptosomal-associated protein SNAP-25 is the major methionine-rich polypeptide in rapid axonal transport and a major substrate for palmitoylation in adult CNS. A conspicuous correlate of the developmental transformation of axonal growth cones to synaptic terminals is a marked increase in synthesis and axonal transport of a methionine-rich, acidic polypeptide of approximately 25 kDa. This polypeptide, designated \"super protein\" (SuP), is the most prominent species among methionine-labeled proteins conveyed by rapid axonal transport in mature CNS and PNS neurons of warm- and cold-blooded vertebrates. We show here that SuP is identical to SNAP-25, a highly conserved synaptic protein of known primary structure, by immunoprecipitation with anti-SNAP-25 antiserum of SuP labeled with 35S-methionine and transported by retinal ganglion cells of rat and cat. In addition, we show that SNAP-25/SuP is the most prominent species among retinal polypeptides that incorporate 3H-palmitate in vivo, that it is fatty acylated through a hydroxylamine-labile, thioester bond, and that palmitoylated SNAP-25/SuP is axonally transported. Thus, SNAP-25/SuP is a rapidly transported constituent of the presynaptic apparatus and a major neuronal substrate for long-chain fatty acylation."} {"id": "PMID:1281491", "title": "Rapid onset of neuronal death induced by blockade of either axoplasmic transport or action potentials in afferent fibers during brain development.", "content": "We have investigated how neurons in the optic tecta of embryonic day 16 chick embryos depend for survival on their afferents from the retina. To distinguish between activity-mediated effects and other, \"trophic,\" ones, we compared the effects on the tectal neurons of blocking intraocular axoplasmic transport (with colchicine) or action potentials (by means of TTX). Both interventions rapidly induced the appearance of dying (pyknotic) neurons in the tectum, with major increases in their number occurring within 13 hr post-colchicine and within 9 hr post-TTX. Following both drugs, the dying neurons were morphologically similar, and in both cases the cell death depended on protein synthesis. However, the effects of colchicine and of TTX could be dissociated, since the most superficial tectal neurons became pyknotic only in response to colchicine, and, with a sufficiently short survival time (9 hr), the deep cells of the stratum griseum centrale became pyknotic only in response to TTX. We hence argue that the survival of the tectal neurons depends on their ongoing maintenance by substances released from retinotectal axon terminals, the release being activity dependent in the case of the deep neurons but independent of activity in the case of the superficial ones.", "contents": "Rapid onset of neuronal death induced by blockade of either axoplasmic transport or action potentials in afferent fibers during brain development. We have investigated how neurons in the optic tecta of embryonic day 16 chick embryos depend for survival on their afferents from the retina. To distinguish between activity-mediated effects and other, \"trophic,\" ones, we compared the effects on the tectal neurons of blocking intraocular axoplasmic transport (with colchicine) or action potentials (by means of TTX). Both interventions rapidly induced the appearance of dying (pyknotic) neurons in the tectum, with major increases in their number occurring within 13 hr post-colchicine and within 9 hr post-TTX. Following both drugs, the dying neurons were morphologically similar, and in both cases the cell death depended on protein synthesis. However, the effects of colchicine and of TTX could be dissociated, since the most superficial tectal neurons became pyknotic only in response to colchicine, and, with a sufficiently short survival time (9 hr), the deep cells of the stratum griseum centrale became pyknotic only in response to TTX. We hence argue that the survival of the tectal neurons depends on their ongoing maintenance by substances released from retinotectal axon terminals, the release being activity dependent in the case of the deep neurons but independent of activity in the case of the superficial ones."} {"id": "PMID:1281492", "title": "c-kit receptor and ligand expression in postnatal development of the mouse cerebellum suggests a function for c-kit in inhibitory interneurons.", "content": "The c-kit receptor and its cognate ligand, KL, are encoded at the white spotting locus (W) and the steel locus (Sl) of the mouse, respectively. Sl and W mutations affect the same cellular targets in melanogenesis, gametogenesis and hematopoiesis during embryonic development and in adult life. c-kit is expressed in cellular targets of W and Sl mutations, whereas KL is expressed in the microenvironment of these targets. c-kit and KL, however, are also expressed in tissues and cell types that are not targets of W and Sl mutations, including the brain. The cerebellum contains a small number of neural cell types whose developmental origins, pathways of migration, and synaptic contacts are known. We have investigated the patterns of expression of the c-kit and KL RNA and protein products in postnatal cerebellar development of the mouse. In the adult cerebellum, c-kit RNA and protein expression was evident in basket, stellate, and Golgi neurons. Most strikingly, the c-kit protein is expressed in the basket cell axons that form \"basket\" and \"pinceau\" structures entwining the Purkinje cell soma and the initial segment of the Purkinje cell axon. KL RNA expression was found in Purkinje cells, and the KL protein was detected in Purkinje cell bodies and dendrites. Soluble KL protein was also present in c-kit-expressing basket, stellate, and Golgi cells, presumably as a result of internalization of ligand-receptor complexes. During postnatal development, c-kit and KL RNA and protein expression in Golgi and Purkinje neurons, respectively, was evident by day 0 and persisted subsequently. c-kit expression in basket and stellate cells was detected from their time of birth, starting at day 4. These results suggest a role for the c-kit receptor system in postnatal development of the cerebellum.", "contents": "c-kit receptor and ligand expression in postnatal development of the mouse cerebellum suggests a function for c-kit in inhibitory interneurons. The c-kit receptor and its cognate ligand, KL, are encoded at the white spotting locus (W) and the steel locus (Sl) of the mouse, respectively. Sl and W mutations affect the same cellular targets in melanogenesis, gametogenesis and hematopoiesis during embryonic development and in adult life. c-kit is expressed in cellular targets of W and Sl mutations, whereas KL is expressed in the microenvironment of these targets. c-kit and KL, however, are also expressed in tissues and cell types that are not targets of W and Sl mutations, including the brain. The cerebellum contains a small number of neural cell types whose developmental origins, pathways of migration, and synaptic contacts are known. We have investigated the patterns of expression of the c-kit and KL RNA and protein products in postnatal cerebellar development of the mouse. In the adult cerebellum, c-kit RNA and protein expression was evident in basket, stellate, and Golgi neurons. Most strikingly, the c-kit protein is expressed in the basket cell axons that form \"basket\" and \"pinceau\" structures entwining the Purkinje cell soma and the initial segment of the Purkinje cell axon. KL RNA expression was found in Purkinje cells, and the KL protein was detected in Purkinje cell bodies and dendrites. Soluble KL protein was also present in c-kit-expressing basket, stellate, and Golgi cells, presumably as a result of internalization of ligand-receptor complexes. During postnatal development, c-kit and KL RNA and protein expression in Golgi and Purkinje neurons, respectively, was evident by day 0 and persisted subsequently. c-kit expression in basket and stellate cells was detected from their time of birth, starting at day 4. These results suggest a role for the c-kit receptor system in postnatal development of the cerebellum."} {"id": "PMID:1281493", "title": "Localization of acidic fibroblast growth factor in specific subcortical neuronal populations.", "content": "The effects of fibroblast growth factors (FGFs) in vitro include the stimulation of mitogenesis in a variety of non-neuronal cell types and the promotion of the survival of various central and peripheral neuronal populations. The precise physiological role of FGFs in vivo is currently not known. As a step toward understanding the role of FGFs in the nervous system, the present study determined the distribution of acidic FGF (aFGF) in the rat CNS. The levels of aFGF in dissected areas of the nervous system were quantified using a biological assay method, and the cellular distribution of aFGF was determined in tissue sections using immunohistochemical methods. aFGF was found to be localized within specific neuronal populations in the CNS and was absent from non-neuronal cells. Neurons containing aFGF immunoreactivity included magnocellular neurons in the septal area and nucleus basalis; some additional defined neuronal groups in the subcortical telencephalon; specific neuronal populations in the hypothalamus, the thalamus, the substantia nigra, the reticular formation, and the pons; and motor and sensory neurons. Cerebral cortex and hippocampus contained only a very limited number of aFGF-immunoreactive neurons. A significant overlap of neuronal populations known to express the low-affinity NGF receptor (LNGFR) with populations containing aFGF immunoreactivity was also observed. These neuronal populations are known to be affected by neurodegenerative diseases, and the possible functional implications of the presence of aFGF and the LNGFR in these cells are discussed.", "contents": "Localization of acidic fibroblast growth factor in specific subcortical neuronal populations. The effects of fibroblast growth factors (FGFs) in vitro include the stimulation of mitogenesis in a variety of non-neuronal cell types and the promotion of the survival of various central and peripheral neuronal populations. The precise physiological role of FGFs in vivo is currently not known. As a step toward understanding the role of FGFs in the nervous system, the present study determined the distribution of acidic FGF (aFGF) in the rat CNS. The levels of aFGF in dissected areas of the nervous system were quantified using a biological assay method, and the cellular distribution of aFGF was determined in tissue sections using immunohistochemical methods. aFGF was found to be localized within specific neuronal populations in the CNS and was absent from non-neuronal cells. Neurons containing aFGF immunoreactivity included magnocellular neurons in the septal area and nucleus basalis; some additional defined neuronal groups in the subcortical telencephalon; specific neuronal populations in the hypothalamus, the thalamus, the substantia nigra, the reticular formation, and the pons; and motor and sensory neurons. Cerebral cortex and hippocampus contained only a very limited number of aFGF-immunoreactive neurons. A significant overlap of neuronal populations known to express the low-affinity NGF receptor (LNGFR) with populations containing aFGF immunoreactivity was also observed. These neuronal populations are known to be affected by neurodegenerative diseases, and the possible functional implications of the presence of aFGF and the LNGFR in these cells are discussed."} {"id": "PMID:1281494", "title": "Coordinate expression of insulin-like growth factor system components by neurons and neuroglia during retinal and cerebellar development.", "content": "The interactions of insulin-like growth factors (IGFs) with the type I IGF receptor are modulated by a family of high-affinity IGF binding proteins (IGFBPs). One of these, IGFBP2, demonstrates a striking spatiotemporal relationship with IGF-I during cerebellar and retinal development. IGF-I mRNA is transiently expressed in large projection neurons--cerebellar Purkinje and retinal ganglion cells--while IGFBP2 mRNA is selectively expressed by contiguous neuroglia--Bergmann glia in the cerebellum and M\u00fcller cells and astrocytes of the nerve fiber layer in the retina. IGF-I and IGFBP2 gene expression is not only neuroanatomically coordinated but also temporally synchronized, peaking together during the postnatal maturation of these structures. This pattern of IGF system expression suggests that IGFBP2 is closely related to IGF-I's action in the developing nervous system.", "contents": "Coordinate expression of insulin-like growth factor system components by neurons and neuroglia during retinal and cerebellar development. The interactions of insulin-like growth factors (IGFs) with the type I IGF receptor are modulated by a family of high-affinity IGF binding proteins (IGFBPs). One of these, IGFBP2, demonstrates a striking spatiotemporal relationship with IGF-I during cerebellar and retinal development. IGF-I mRNA is transiently expressed in large projection neurons--cerebellar Purkinje and retinal ganglion cells--while IGFBP2 mRNA is selectively expressed by contiguous neuroglia--Bergmann glia in the cerebellum and M\u00fcller cells and astrocytes of the nerve fiber layer in the retina. IGF-I and IGFBP2 gene expression is not only neuroanatomically coordinated but also temporally synchronized, peaking together during the postnatal maturation of these structures. This pattern of IGF system expression suggests that IGFBP2 is closely related to IGF-I's action in the developing nervous system."} {"id": "PMID:1281495", "title": "Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes.", "content": "Brain-derived neurotrophic factor (BDNF) and NGF are both expressed by neurons in the hippocampus. In previous studies, it has been demonstrated that both BDNF and NGF mRNA levels are regulated by neuronal activity. Upregulation is predominantly regulated by the glutamate (NMDA and non-NMDA receptors); downregulation, predominantly by the GABA system (Zafra et al., 1990, 1991). In neuronal cultures of the rat hippocampus, potassium depolarization and kainic acid-mediated increases in BDNF and NGF mRNA were eliminated in a dose-dependent manner by the calcium channel blocker nifedipine. Conversely, calcium ionophores (Bay-K8644 and ionomycin) augmented BDNF and NGF mRNA levels by a calmodulin-mediated mechanism. In view of the fact that many potential modulators (conventional transmitters and neuropeptides) of neuronal and astrocytic BDNF and NGF mRNA synthesis may act via the adenylate cyclase system, we studied the effect of forskolin, an activator of adenylate cyclase. Indeed, forskolin enhanced the effects of calcium ionophores and kainic acid on BDNF and NGF mRNA levels. Cytokines, such as interleukin-1 and transforming growth factor-beta 1, which have previously been shown to increase NGF mRNA markedly in astrocytes, were without effect on neuronal BDNF and NGF mRNA levels. In contrast to neuronal cultures, where the regulation of BDNF and NGF mRNA was generally very similar, the regulation in astrocytes was distinctly different. All the cytokines that produce a marked increase in NGF mRNA were without effect on astrocyte BDNF mRNA levels, which under basic conditions were below the detection limit. However, norepinephrine produced a marked elevation of BDNF mRNA in astrocytes, an effect that was further enhanced by glutamate receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Regulation of brain-derived neurotrophic factor and nerve growth factor mRNA in primary cultures of hippocampal neurons and astrocytes. Brain-derived neurotrophic factor (BDNF) and NGF are both expressed by neurons in the hippocampus. In previous studies, it has been demonstrated that both BDNF and NGF mRNA levels are regulated by neuronal activity. Upregulation is predominantly regulated by the glutamate (NMDA and non-NMDA receptors); downregulation, predominantly by the GABA system (Zafra et al., 1990, 1991). In neuronal cultures of the rat hippocampus, potassium depolarization and kainic acid-mediated increases in BDNF and NGF mRNA were eliminated in a dose-dependent manner by the calcium channel blocker nifedipine. Conversely, calcium ionophores (Bay-K8644 and ionomycin) augmented BDNF and NGF mRNA levels by a calmodulin-mediated mechanism. In view of the fact that many potential modulators (conventional transmitters and neuropeptides) of neuronal and astrocytic BDNF and NGF mRNA synthesis may act via the adenylate cyclase system, we studied the effect of forskolin, an activator of adenylate cyclase. Indeed, forskolin enhanced the effects of calcium ionophores and kainic acid on BDNF and NGF mRNA levels. Cytokines, such as interleukin-1 and transforming growth factor-beta 1, which have previously been shown to increase NGF mRNA markedly in astrocytes, were without effect on neuronal BDNF and NGF mRNA levels. In contrast to neuronal cultures, where the regulation of BDNF and NGF mRNA was generally very similar, the regulation in astrocytes was distinctly different. All the cytokines that produce a marked increase in NGF mRNA were without effect on astrocyte BDNF mRNA levels, which under basic conditions were below the detection limit. However, norepinephrine produced a marked elevation of BDNF mRNA in astrocytes, an effect that was further enhanced by glutamate receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281496", "title": "Visualization of O-2A progenitor cells in developing and adult rat optic nerve by quisqualate-stimulated cobalt uptake.", "content": "Some macroglial cells of the O-2A lineage express glutamate receptor channels of the quisqualate/kainate type and take up extracellular cobalt when activated by glutamate agonists. These cells can be identified both in vitro and in situ following precipitation and intensification of the intracellular cobalt. We have used this technique to characterize these cells in the developing and adult rat optic nerve. In purified cultures of optic nerve cells, O-2A progenitor cells and type 2 astrocytes took up cobalt in the presence of quisqualate, while oligodendrocytes, type 1 astrocytes, and microglial cells did not. When whole optic nerves of various postnatal ages were exposed to quisqualate and cobalt, a subpopulation of glial cells took up cobalt. Cobalt uptake in vitro and in situ was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. The number, morphology, and spatial distribution of cobalt-filled cells in situ varied with age. In perinatal nerves, 9% of glial cells took up cobalt. These cells had a simple unipolar or bipolar morphology and were two to three times more concentrated at the chiasm end than at the eye end of the nerve. During subsequent development, this gradient disappeared and the cobalt-filled cells became progressively more complex in morphology and increased in number and density, reaching a peak toward the end of the second postnatal week. The number subsequently declined to about 16,000 (7%) in the adult nerve. The processes of some cobalt-filled cells appeared to contact nodes of Ranvier. All cobalt-filled cells in 2 1/2-week-old optic nerves had a similar ultrastructural appearance and did not resemble either mature oligodendrocytes or astrocytes. Our results suggest that the cells stimulated by quisqualate to take up cobalt in the optic nerve are the in vivo counterpart of O-2A progenitor cells. We found no evidence that any of these cells are type 2 astrocytes.", "contents": "Visualization of O-2A progenitor cells in developing and adult rat optic nerve by quisqualate-stimulated cobalt uptake. Some macroglial cells of the O-2A lineage express glutamate receptor channels of the quisqualate/kainate type and take up extracellular cobalt when activated by glutamate agonists. These cells can be identified both in vitro and in situ following precipitation and intensification of the intracellular cobalt. We have used this technique to characterize these cells in the developing and adult rat optic nerve. In purified cultures of optic nerve cells, O-2A progenitor cells and type 2 astrocytes took up cobalt in the presence of quisqualate, while oligodendrocytes, type 1 astrocytes, and microglial cells did not. When whole optic nerves of various postnatal ages were exposed to quisqualate and cobalt, a subpopulation of glial cells took up cobalt. Cobalt uptake in vitro and in situ was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. The number, morphology, and spatial distribution of cobalt-filled cells in situ varied with age. In perinatal nerves, 9% of glial cells took up cobalt. These cells had a simple unipolar or bipolar morphology and were two to three times more concentrated at the chiasm end than at the eye end of the nerve. During subsequent development, this gradient disappeared and the cobalt-filled cells became progressively more complex in morphology and increased in number and density, reaching a peak toward the end of the second postnatal week. The number subsequently declined to about 16,000 (7%) in the adult nerve. The processes of some cobalt-filled cells appeared to contact nodes of Ranvier. All cobalt-filled cells in 2 1/2-week-old optic nerves had a similar ultrastructural appearance and did not resemble either mature oligodendrocytes or astrocytes. Our results suggest that the cells stimulated by quisqualate to take up cobalt in the optic nerve are the in vivo counterpart of O-2A progenitor cells. We found no evidence that any of these cells are type 2 astrocytes."} {"id": "PMID:1281497", "title": "Myelin acquisition in the central nervous system of the mouse revealed by an MBP-Lac Z transgene.", "content": "Myelin has pronounced effects upon the morphology, function, and growth of axons in the mammalian CNS. Consequently, oligodendrocyte development and myelination have been investigated using a wide variety of histological, immunocytochemical, ultrastructural, and biochemical techniques. While many of the spatial and temporal features of myelin appearance have been characterized, for any one species only limited regions of the CNS have been investigated. To address this limitation, we have derived transgenic mice in which the bacterial Lac Z gene is regulated by promoter elements of the myelin basic protein gene. When differentiating oligodendrocytes begin to elaborate recognizable myelin, they initiate expression of the MBP-Lac Z transgene and accumulate readily detectable levels of beta-galactosidase. Here, we exploit the sensitivity, resolution, and ease of beta-galactosidase histochemical assays to characterize the temporal and spatial patterns of CNS myelination in the mouse. Many features of the myelination program revealed by this approach were predicted by the immunocytochemical and ultrastructural data derived from other species. Nonetheless, previously undocumented patterns were also encountered. beta-Galactosidase was expressed first by oligodendrocytes in the ventral spinal cord, 1 d prior to birth. There, myelination proceeded in a strictly rostral-caudal direction, whereas in the dorsal cord, myelination initiated in the cervical enlargement and proceeded in both rostral and caudal directions. In the cerebellum, deep regions myelinated first, and in the optic nerve, myelination initiated at the retinal end. In contrast, the lateral olfactory tracts, pons, and optic chiasm initiated myelination along their entire course.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Myelin acquisition in the central nervous system of the mouse revealed by an MBP-Lac Z transgene. Myelin has pronounced effects upon the morphology, function, and growth of axons in the mammalian CNS. Consequently, oligodendrocyte development and myelination have been investigated using a wide variety of histological, immunocytochemical, ultrastructural, and biochemical techniques. While many of the spatial and temporal features of myelin appearance have been characterized, for any one species only limited regions of the CNS have been investigated. To address this limitation, we have derived transgenic mice in which the bacterial Lac Z gene is regulated by promoter elements of the myelin basic protein gene. When differentiating oligodendrocytes begin to elaborate recognizable myelin, they initiate expression of the MBP-Lac Z transgene and accumulate readily detectable levels of beta-galactosidase. Here, we exploit the sensitivity, resolution, and ease of beta-galactosidase histochemical assays to characterize the temporal and spatial patterns of CNS myelination in the mouse. Many features of the myelination program revealed by this approach were predicted by the immunocytochemical and ultrastructural data derived from other species. Nonetheless, previously undocumented patterns were also encountered. beta-Galactosidase was expressed first by oligodendrocytes in the ventral spinal cord, 1 d prior to birth. There, myelination proceeded in a strictly rostral-caudal direction, whereas in the dorsal cord, myelination initiated in the cervical enlargement and proceeded in both rostral and caudal directions. In the cerebellum, deep regions myelinated first, and in the optic nerve, myelination initiated at the retinal end. In contrast, the lateral olfactory tracts, pons, and optic chiasm initiated myelination along their entire course.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281498", "title": "Amino terminus of substance P potentiates kainic acid-induced activity in the mouse spinal cord.", "content": "Sensitization to the behavioral effects produced by repeated injections of kainic acid (KA) into the mouse spinal cord area has been previously shown to be abolished by pretreatment with capsaicin, a neurotoxin of substance P (SP)-containing primary afferent C-fibers. While SP has a variety of well characterized biological actions that are mediated by interactions of its COOH terminus with neurokinin receptors, more recently we have characterized an amino-terminally directed SP binding site. The present studies were initiated to determine whether behavioral sensitization to repeated injections of intrathecally administered KA is mediated by the COOH or NH2 terminal of SP. In the present studies, pretreatment with SP(1-7), an NH2-terminal fragment of SP, but not SP(5-11), a COOH-terminal fragment, potentiated KA-induced behavioral activity in mice. Pretreatment with [D-Pro2,D-Phe7]SP(1-7), an inhibitor of SP NH2-terminal binding, blocked the potentiative effect of SP(1-7) as well as the sensitization to repeated injections of KA. In contrast, [D-Pro2,D-Trp7,9]SP, a neurokinin antagonist, had little effect on behavioral sensitization to KA. The present study suggests that SP has an important modulatory role on excitatory amino acid activity in the spinal cord that is mediated by an action of the NH2 terminal of SP at a non-neurokinin receptor.", "contents": "Amino terminus of substance P potentiates kainic acid-induced activity in the mouse spinal cord. Sensitization to the behavioral effects produced by repeated injections of kainic acid (KA) into the mouse spinal cord area has been previously shown to be abolished by pretreatment with capsaicin, a neurotoxin of substance P (SP)-containing primary afferent C-fibers. While SP has a variety of well characterized biological actions that are mediated by interactions of its COOH terminus with neurokinin receptors, more recently we have characterized an amino-terminally directed SP binding site. The present studies were initiated to determine whether behavioral sensitization to repeated injections of intrathecally administered KA is mediated by the COOH or NH2 terminal of SP. In the present studies, pretreatment with SP(1-7), an NH2-terminal fragment of SP, but not SP(5-11), a COOH-terminal fragment, potentiated KA-induced behavioral activity in mice. Pretreatment with [D-Pro2,D-Phe7]SP(1-7), an inhibitor of SP NH2-terminal binding, blocked the potentiative effect of SP(1-7) as well as the sensitization to repeated injections of KA. In contrast, [D-Pro2,D-Trp7,9]SP, a neurokinin antagonist, had little effect on behavioral sensitization to KA. The present study suggests that SP has an important modulatory role on excitatory amino acid activity in the spinal cord that is mediated by an action of the NH2 terminal of SP at a non-neurokinin receptor."} {"id": "PMID:1281499", "title": "Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina.", "content": "In mammalian retina, the rod bipolar cells synapse on the AII amacrine cells, which are therefore the third-order neurons in the rod-signal pathway. The AII amacrine cells are connected by gap junctions, both to each other and to fourth-order, On-center cone bipolar cells. They also receive synaptic input from the dopaminergic amacrine cells, and in this study, we investigated whether dopamine modulates the permeability of the gap junctions between AII amacrine cells in the isolated rabbit retina. The small biotinylated tracer Neurobiotin was injected into nuclear yellow-labeled AII cells under direct microscopic control. The extent of tracer coupling to neighboring AII cells, 40-60 min after Neurobiotin injection (0.5 nA for 60 sec), provided a standard measure of the permeability of the homologous gap junctions. Under control conditions, individual AII amacrine cells were coupled to 73 +/- 15 neighboring cells, and this was unaffected by changes in pH from 6.6 to 7.8. Exogenous dopamine significantly reduced the tracer coupling at concentrations as low as 10 nM (26 +/- 16 cells), with the effect increasing with dopamine concentration up to 10 microM (6 +/- 4 cells). The uncoupling effect of dopamine was both blocked by the selective D1 antagonist SCH-23390 (10 microM) and mimicked by the specific D1 agonist SKF-38393 (500 microM). Moreover, the AII amacrine cells were also uncoupled when the retina was incubated in forskolin (60 microM) and isobutylmethylxanthine (200 microM). Taken together, these results indicated that the uncoupling was mediated by a D1-like receptor that stimulates cAMP production. Although the selective D1 antagonist on its own did not increase tracer coupling, suggesting that there was little release of endogenous dopamine in the superfused photo-bleached retina, veratridine-evoked release of endogenous transmitters did uncouple the AII amacrine cells, and this effect was blocked by the specific D1 antagonist.", "contents": "Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina. In mammalian retina, the rod bipolar cells synapse on the AII amacrine cells, which are therefore the third-order neurons in the rod-signal pathway. The AII amacrine cells are connected by gap junctions, both to each other and to fourth-order, On-center cone bipolar cells. They also receive synaptic input from the dopaminergic amacrine cells, and in this study, we investigated whether dopamine modulates the permeability of the gap junctions between AII amacrine cells in the isolated rabbit retina. The small biotinylated tracer Neurobiotin was injected into nuclear yellow-labeled AII cells under direct microscopic control. The extent of tracer coupling to neighboring AII cells, 40-60 min after Neurobiotin injection (0.5 nA for 60 sec), provided a standard measure of the permeability of the homologous gap junctions. Under control conditions, individual AII amacrine cells were coupled to 73 +/- 15 neighboring cells, and this was unaffected by changes in pH from 6.6 to 7.8. Exogenous dopamine significantly reduced the tracer coupling at concentrations as low as 10 nM (26 +/- 16 cells), with the effect increasing with dopamine concentration up to 10 microM (6 +/- 4 cells). The uncoupling effect of dopamine was both blocked by the selective D1 antagonist SCH-23390 (10 microM) and mimicked by the specific D1 agonist SKF-38393 (500 microM). Moreover, the AII amacrine cells were also uncoupled when the retina was incubated in forskolin (60 microM) and isobutylmethylxanthine (200 microM). Taken together, these results indicated that the uncoupling was mediated by a D1-like receptor that stimulates cAMP production. Although the selective D1 antagonist on its own did not increase tracer coupling, suggesting that there was little release of endogenous dopamine in the superfused photo-bleached retina, veratridine-evoked release of endogenous transmitters did uncouple the AII amacrine cells, and this effect was blocked by the specific D1 antagonist."} {"id": "PMID:1281501", "title": "[A contralateral external carotid-middle cerebral artery bypass operation--a new procedure of vascular reconstruction in the treatment of head and neck carcinoma requiring carotid resection].", "content": "In the treatment of head and neck carcinoma involving the carotid artery, resection of the carotid artery and direct reconstruction using a vein graft has commonly been employed to reduce the incidence of cerebral ischemic complications. But the procedure of carotid grafting itself carries the risk of preventing complete tumor clearance. And contamination due to salivary fistula, particularly in cases of meso or hypopharyngeal carcinoma, may result in graft rupture or thrombosis. To overcome these difficulties, the authors have developed a new surgical procedure, namely, a contralateral external carotid-middle cerebral artery bypass operation. This bypass system is designed at directly supplying the cerebral hemisphere on the carotid ligation side through a vein graft running entirely outside the cervical operative field. The vein graft is anastomosed end-to side to the external carotid artery of the opposite side. Then it is placed subcutaneously in front of the auricle, above the zygomatic arch, frontal subgaleal space and anastomosed end-to-side to the recipient artery, the ascending branch of the middle cerebral artery, in the Broca area of the carotid ligation side. The neck is incised almost the same manner as in parotidectomy, with a slightly longer cervical extension, and the scalp by bilateral coronal incision of Sutta. A frontotemporal osteoplastic craniotomy of the involved side is performed. The length of the saphenous vein used is about 50cm. This surgical procedure requires no transient internal or external shunt. The common carotid artery can be ligated safely after confirming good post-anastomotic bypass flow using an electro-magnetic blood flow meter.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[A contralateral external carotid-middle cerebral artery bypass operation--a new procedure of vascular reconstruction in the treatment of head and neck carcinoma requiring carotid resection]. In the treatment of head and neck carcinoma involving the carotid artery, resection of the carotid artery and direct reconstruction using a vein graft has commonly been employed to reduce the incidence of cerebral ischemic complications. But the procedure of carotid grafting itself carries the risk of preventing complete tumor clearance. And contamination due to salivary fistula, particularly in cases of meso or hypopharyngeal carcinoma, may result in graft rupture or thrombosis. To overcome these difficulties, the authors have developed a new surgical procedure, namely, a contralateral external carotid-middle cerebral artery bypass operation. This bypass system is designed at directly supplying the cerebral hemisphere on the carotid ligation side through a vein graft running entirely outside the cervical operative field. The vein graft is anastomosed end-to side to the external carotid artery of the opposite side. Then it is placed subcutaneously in front of the auricle, above the zygomatic arch, frontal subgaleal space and anastomosed end-to-side to the recipient artery, the ascending branch of the middle cerebral artery, in the Broca area of the carotid ligation side. The neck is incised almost the same manner as in parotidectomy, with a slightly longer cervical extension, and the scalp by bilateral coronal incision of Sutta. A frontotemporal osteoplastic craniotomy of the involved side is performed. The length of the saphenous vein used is about 50cm. This surgical procedure requires no transient internal or external shunt. The common carotid artery can be ligated safely after confirming good post-anastomotic bypass flow using an electro-magnetic blood flow meter.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281502", "title": "Acetylcholine activates non-selective cation and chloride conductances in canine and guinea-pig tracheal myocytes.", "content": "1. Membrane currents activated by acetylcholine (ACh) were investigated in isolated canine and guinea-pig tracheal myocytes using the nystatin perforated patch configuration of whole-cell recording. ACh caused depolarization accompanied by a membrane conductance increase. 2. When cells were held under voltage clamp (holding potential, Vh = -60 mV), ACh elicited inward current (IACh) of up to 3900 pA, with a reversal potential (Erev) of approximately -20 mV. 3. Removal of extracellular Na+ (Na+o) reduced but did not eliminate IACh. IACh remaining in the absence of Na+ reversed direction close to the predicted equilibrium potential for Cl-. Erev shifted 32 +/- 4 mV per 10-fold change of [Cl-]i. Increasing external [K+] caused Erev to shift in the positive direction. These results suggest that ACh activated chloride and non-selective cation conductances. 4. In the absence of Na+o, the Cl- channel blockers SITS or niflumic acid reversibly antagonized IACh. 5. Caffeine and ryanodine elicited currents both in the presence and absence of Na+o; these currents had a reversal potential similar to that of IACh. Caffeine applied before ACh occluded the response to ACh. 6. We also observed two types of spontaneous membrane currents. Spontaneous transient outward currents (STOCs) may represent Ca(2+)-activated K+ currents. Spontaneous inward currents were also observed which were reduced in magnitude (but not eliminated) by removal of Na+o and reversed direction at approximately the Cl- equilibrium potential. The spontaneous inward currents and STOCs were coincident and were reversibly suppressed by ACh. 7. ACh elicited contractions of cells under voltage clamp at -60 mV, an effect also observed in the absence of extracellular Ca2+ or when IACh was reduced by omission of Na+o and exposure to Cl- channel blockers. The number of cells which did contract in response to ACh decreased, however, when the concentration of internal Cl- decreased. 8. All effects of ACh on contraction and membrane currents were antagonized by atropine. 9. We conclude that activation of muscarinic receptors in mammalian tracheal myocytes causes release of Ca2+ from intracellular stores and subsequent activation of Cl- and non-selective cation conductances. This is the first direct demonstration of these conductances in tracheal smooth muscle cells. Activation of these conductances does not appear to be required for contraction. However, regulation of cytosolic Cl- levels may be important for release and uptake of Ca2+ from internal stores.", "contents": "Acetylcholine activates non-selective cation and chloride conductances in canine and guinea-pig tracheal myocytes. 1. Membrane currents activated by acetylcholine (ACh) were investigated in isolated canine and guinea-pig tracheal myocytes using the nystatin perforated patch configuration of whole-cell recording. ACh caused depolarization accompanied by a membrane conductance increase. 2. When cells were held under voltage clamp (holding potential, Vh = -60 mV), ACh elicited inward current (IACh) of up to 3900 pA, with a reversal potential (Erev) of approximately -20 mV. 3. Removal of extracellular Na+ (Na+o) reduced but did not eliminate IACh. IACh remaining in the absence of Na+ reversed direction close to the predicted equilibrium potential for Cl-. Erev shifted 32 +/- 4 mV per 10-fold change of [Cl-]i. Increasing external [K+] caused Erev to shift in the positive direction. These results suggest that ACh activated chloride and non-selective cation conductances. 4. In the absence of Na+o, the Cl- channel blockers SITS or niflumic acid reversibly antagonized IACh. 5. Caffeine and ryanodine elicited currents both in the presence and absence of Na+o; these currents had a reversal potential similar to that of IACh. Caffeine applied before ACh occluded the response to ACh. 6. We also observed two types of spontaneous membrane currents. Spontaneous transient outward currents (STOCs) may represent Ca(2+)-activated K+ currents. Spontaneous inward currents were also observed which were reduced in magnitude (but not eliminated) by removal of Na+o and reversed direction at approximately the Cl- equilibrium potential. The spontaneous inward currents and STOCs were coincident and were reversibly suppressed by ACh. 7. ACh elicited contractions of cells under voltage clamp at -60 mV, an effect also observed in the absence of extracellular Ca2+ or when IACh was reduced by omission of Na+o and exposure to Cl- channel blockers. The number of cells which did contract in response to ACh decreased, however, when the concentration of internal Cl- decreased. 8. All effects of ACh on contraction and membrane currents were antagonized by atropine. 9. We conclude that activation of muscarinic receptors in mammalian tracheal myocytes causes release of Ca2+ from intracellular stores and subsequent activation of Cl- and non-selective cation conductances. This is the first direct demonstration of these conductances in tracheal smooth muscle cells. Activation of these conductances does not appear to be required for contraction. However, regulation of cytosolic Cl- levels may be important for release and uptake of Ca2+ from internal stores."} {"id": "PMID:1281503", "title": "Voltage-dependent gating mechanism for single fast chloride channels from rat skeletal muscle.", "content": "1. A voltage-dependent gating mechanism for the fast Cl- channel was developed from the analysis of single-channel current records obtained with the patch clamp technique from primary cultures of rat skeletal muscle. Up to 10(6) open and shut intervals were analysed from each of five different excised patches of membrane containing a single fast Cl- channel. 2. Rate constants for a kinetic scheme with six closed and two open states (scheme I) were estimated at a given voltage by maximum likelihood fitting of open and closed dwell-time distributions obtained at that voltage. This procedure was then repeated for data obtained at each of three to eight different membrane potentials for each channel. 3. Plots of the estimated rate constants against membrane potential typically appeared linear on semilogarithmic co-ordinates, consistent with rate constants that are exponentially dependent on voltage. 4. Regression analysis of these plots yielded two parameters for each rate constant: the value of the rate constant at -50 mV (B) and its voltage sensitivity (A). The dwell-time distributions predicted with these parameters and scheme I gave a good description of the experimental dwell-time distributions at all the studied voltages, lending further support for an exponential dependence of rate constants on membrane potential. 5. Estimates of A and B were also obtained by simultaneously fitting dwell-time distributions obtained at three to eight different voltages, in order to better define these parameters. Predicted dwell-time distributions obtained with these estimates and scheme I could approach the theoretical best description of the data for discrete-state Markov models. 6. Eight to twelve of the fourteen rate constants in scheme I appeared voltage sensitive, with effective gating charges ranging from about -1.5 to +1.0 units of electronic charge. 7. The estimated rate constants and their voltage sensitivities for the five analysed channels were generally similar, but showed some heterogeneity. 8. Gating mechanisms which had fewer kinetic states than scheme I, or equal and opposite effective gating charges over each transition barrier, or four or five identical and independent voltage-dependent subunits, all gave poorer descriptions of the data than scheme I. These simpler mechanisms were also ranked below scheme I by the Schwarz criterion, which applies a heavy penalty for additional free parameters. 9. These findings indicate that the voltage dependence of the fast Cl- channel is consistent with a kinetic scheme with six closed and two open states, in which a majority of transitions among the states are voltage dependent.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Voltage-dependent gating mechanism for single fast chloride channels from rat skeletal muscle. 1. A voltage-dependent gating mechanism for the fast Cl- channel was developed from the analysis of single-channel current records obtained with the patch clamp technique from primary cultures of rat skeletal muscle. Up to 10(6) open and shut intervals were analysed from each of five different excised patches of membrane containing a single fast Cl- channel. 2. Rate constants for a kinetic scheme with six closed and two open states (scheme I) were estimated at a given voltage by maximum likelihood fitting of open and closed dwell-time distributions obtained at that voltage. This procedure was then repeated for data obtained at each of three to eight different membrane potentials for each channel. 3. Plots of the estimated rate constants against membrane potential typically appeared linear on semilogarithmic co-ordinates, consistent with rate constants that are exponentially dependent on voltage. 4. Regression analysis of these plots yielded two parameters for each rate constant: the value of the rate constant at -50 mV (B) and its voltage sensitivity (A). The dwell-time distributions predicted with these parameters and scheme I gave a good description of the experimental dwell-time distributions at all the studied voltages, lending further support for an exponential dependence of rate constants on membrane potential. 5. Estimates of A and B were also obtained by simultaneously fitting dwell-time distributions obtained at three to eight different voltages, in order to better define these parameters. Predicted dwell-time distributions obtained with these estimates and scheme I could approach the theoretical best description of the data for discrete-state Markov models. 6. Eight to twelve of the fourteen rate constants in scheme I appeared voltage sensitive, with effective gating charges ranging from about -1.5 to +1.0 units of electronic charge. 7. The estimated rate constants and their voltage sensitivities for the five analysed channels were generally similar, but showed some heterogeneity. 8. Gating mechanisms which had fewer kinetic states than scheme I, or equal and opposite effective gating charges over each transition barrier, or four or five identical and independent voltage-dependent subunits, all gave poorer descriptions of the data than scheme I. These simpler mechanisms were also ranked below scheme I by the Schwarz criterion, which applies a heavy penalty for additional free parameters. 9. These findings indicate that the voltage dependence of the fast Cl- channel is consistent with a kinetic scheme with six closed and two open states, in which a majority of transitions among the states are voltage dependent.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281504", "title": "Control of the hyperpolarization-activated cation current by external anions in rabbit sino-atrial node cells.", "content": "1. Effects of varying concentrations of anions on the hyperpolarization-activated current (I(f)) were studied in myocytes isolated from the rabbit sino-atrial node. Substituting Cs+ for the intracellular K+ clearly separated I(f) from the delayed rectifier K+ current. Control properties, including gating kinetics and ion selectivity, similar to previous studies were obtained. 2. Substitution of extracellular Cl- with larger anions including isethionate, glutamate, acetate, and aspartate, reduced the amplitude of I(f) without changing the reversal potential. Substitution with small anions such as iodide or nitrate supported an intact I(f). These effects were reproduced in the excised outside-out patch conformation. 3. The conductance for I(f) was a saturating function of the extracellular Cl- concentration ([Cl-]o) with an equilibrium binding constant (K1/2) of 11 mM and a slope factor of about 1 when substituted with large anions. Total removal of small anions completely abolished I(f). 4. The voltage-dependent gating of I(f) was not affected by changing ([Cl-]o), suggesting that Cl- modulates conductance properties of I(f). 5. The results indicate that I(f) conductance is unique in that it is dependent on an extracellular anion (Cl-), yet it is carried exclusively by cations, K+ and Na+. These effects are independent of any measurable voltage-dependent gating parameters.", "contents": "Control of the hyperpolarization-activated cation current by external anions in rabbit sino-atrial node cells. 1. Effects of varying concentrations of anions on the hyperpolarization-activated current (I(f)) were studied in myocytes isolated from the rabbit sino-atrial node. Substituting Cs+ for the intracellular K+ clearly separated I(f) from the delayed rectifier K+ current. Control properties, including gating kinetics and ion selectivity, similar to previous studies were obtained. 2. Substitution of extracellular Cl- with larger anions including isethionate, glutamate, acetate, and aspartate, reduced the amplitude of I(f) without changing the reversal potential. Substitution with small anions such as iodide or nitrate supported an intact I(f). These effects were reproduced in the excised outside-out patch conformation. 3. The conductance for I(f) was a saturating function of the extracellular Cl- concentration ([Cl-]o) with an equilibrium binding constant (K1/2) of 11 mM and a slope factor of about 1 when substituted with large anions. Total removal of small anions completely abolished I(f). 4. The voltage-dependent gating of I(f) was not affected by changing ([Cl-]o), suggesting that Cl- modulates conductance properties of I(f). 5. The results indicate that I(f) conductance is unique in that it is dependent on an extracellular anion (Cl-), yet it is carried exclusively by cations, K+ and Na+. These effects are independent of any measurable voltage-dependent gating parameters."} {"id": "PMID:1281505", "title": "Properties of the pacemaker current (If) in latent pacemaker cells isolated from cat right atrium.", "content": "1. Single latent pacemaker cells were isolated from the Eustachian ridge of cat right atrium using Langendorff perfusion and enzyme dispersion techniques. Whole-cell patch-clamp techniques were used to study the hyperpolarization-activated inward current (I(f)). 2. All cells studied beat rhythmically. Pacemaker activity was recorded in the voltage range -68 +/- 1 to -54 +/- 2 mV and its cycle length was 901 +/- 67 ms (72 +/- 5 beats min-1) at 34-36 degrees C. Cells were elongated with tapered ends, and appeared bent or crinkled without obvious striations. Mean cell diameter and length were 7.4 +/- 0.5 microns and 93.1 +/- 5.9 microns, respectively (n = 15). Input resistance and total membrane capacitance were 2.2 +/- 0.2 G omega and 27.8 +/- 3.1 pF, respectively. 3. Hyperpolarizing clamp steps more negative than -50 mV elicited a time-dependent increasing inward current that was maximally activated at -120 mV. Activation of I(f) was well within the pacemaker voltage range. Half-maximal activation voltage and slope factor were calculated, using a Boltzmann function, to be -80.5 mV and 8.4, respectively. 4. The fully activated current-voltage (I-V) relationship was approximately linear at voltages more negative than -30 mV and showed outward rectification at more positive voltages. The reversal potential of I(f) was -26 mV and the fully activated conductance was 1.75 +/- 0.14 nS (n = 21). Caesium (2 mM) blocked I(f) at voltages more negative than the reversal potential. Reducing extracellular Na+ or K+ shifted the reversal potential more negative, and increasing extracellular K+ exerted the opposite effect. Reducing extracellular Na+ decreased I(f) amplitude and the slope of the fully activated I-V relationship, and elevated extracellular K+ increased I(f) amplitude and the slope of the fully activated I-V relationship. 5. Some pacemaker cells exhibited a short delay in the onset of I(f) activation whereas other pacemaker cells exhibited little, if any, delay in activation. I(f) currents exhibiting no delay in activation were best fitted by a single exponential function with a mean time constant of 3.20 +/- 1.03 s at -70 mV (n = 4). 6. A nystatin-permeabilized patch recording method was used to record spontaneous pacemaker action potentials and I(f) from the same pacemaker cell. Caesium (2 mM) inhibited I(f) by more than 90% (at -70 mV), and decreased the slope of diastolic depolarization, resulting in a 48 +/- 5% decrease in spontaneous rate.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Properties of the pacemaker current (If) in latent pacemaker cells isolated from cat right atrium. 1. Single latent pacemaker cells were isolated from the Eustachian ridge of cat right atrium using Langendorff perfusion and enzyme dispersion techniques. Whole-cell patch-clamp techniques were used to study the hyperpolarization-activated inward current (I(f)). 2. All cells studied beat rhythmically. Pacemaker activity was recorded in the voltage range -68 +/- 1 to -54 +/- 2 mV and its cycle length was 901 +/- 67 ms (72 +/- 5 beats min-1) at 34-36 degrees C. Cells were elongated with tapered ends, and appeared bent or crinkled without obvious striations. Mean cell diameter and length were 7.4 +/- 0.5 microns and 93.1 +/- 5.9 microns, respectively (n = 15). Input resistance and total membrane capacitance were 2.2 +/- 0.2 G omega and 27.8 +/- 3.1 pF, respectively. 3. Hyperpolarizing clamp steps more negative than -50 mV elicited a time-dependent increasing inward current that was maximally activated at -120 mV. Activation of I(f) was well within the pacemaker voltage range. Half-maximal activation voltage and slope factor were calculated, using a Boltzmann function, to be -80.5 mV and 8.4, respectively. 4. The fully activated current-voltage (I-V) relationship was approximately linear at voltages more negative than -30 mV and showed outward rectification at more positive voltages. The reversal potential of I(f) was -26 mV and the fully activated conductance was 1.75 +/- 0.14 nS (n = 21). Caesium (2 mM) blocked I(f) at voltages more negative than the reversal potential. Reducing extracellular Na+ or K+ shifted the reversal potential more negative, and increasing extracellular K+ exerted the opposite effect. Reducing extracellular Na+ decreased I(f) amplitude and the slope of the fully activated I-V relationship, and elevated extracellular K+ increased I(f) amplitude and the slope of the fully activated I-V relationship. 5. Some pacemaker cells exhibited a short delay in the onset of I(f) activation whereas other pacemaker cells exhibited little, if any, delay in activation. I(f) currents exhibiting no delay in activation were best fitted by a single exponential function with a mean time constant of 3.20 +/- 1.03 s at -70 mV (n = 4). 6. A nystatin-permeabilized patch recording method was used to record spontaneous pacemaker action potentials and I(f) from the same pacemaker cell. Caesium (2 mM) inhibited I(f) by more than 90% (at -70 mV), and decreased the slope of diastolic depolarization, resulting in a 48 +/- 5% decrease in spontaneous rate.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281506", "title": "Synergistic action of cyclic GMP on catecholamine-induced chloride current in guinea-pig ventricular cells.", "content": "1. Effects of cyclic GMP on the catecholamine-induced chloride current (ICl) were studied using the whole-cell patch-clamp technique combined with internal perfusion in single ventricular myocytes dispersed from guinea-pig heart. 2. When ICl was activated by submaximal doses of isoprenaline (0.01-0.1 microM), adrenaline (0.5-1 microM) and histamine (0.2-0.5 microM), intracellular dialysis with cyclic GMP (10-100 microM) induced an extra increase of ICl. No further increase of ICl was induced by cyclic GMP when ICl was maximally activated. In the absence of agonists, cyclic GMP failed to induce ICl. 3. The enhancement by cyclic GMP was also observed when ICl was activated by external application of 0.2-1.0 microM-forskolin or by internal dialysis with a pipette solution containing 50-200 microM-cyclic AMP. 4. In contrast to cyclic GMP, 10-1000 microM-dibutyryl cyclic GMP and 8-bromo-cyclic GMP were ineffective in modifying ICl. 5. Milrinone (1-10 microM), a specific inhibitor of a kind of phosphodiesterase which is inhibited by cyclic GMP, also enhanced ICl activated by submaximal doses of isoprenaline. Milrinone itself did not activate ICl. 6. When ICl was enhanced by 5 microM-milrinone, an additional application of cyclic GMP failed to increase ICl. In the presence of cyclic GMP, milrinone failed to enhance ICl. 7. The above findings on ICl are analogous to the enhancement by cyclic GMP of the beta-adrenergic stimulation of the Ca2+ current reported in the same preparation, and support the hypothesis that in mammalian cardiac cells cyclic GMP potentiates elevation of cyclic AMP induced by beta-adrenergic agents, and thereby increases the amplitudes of ionic currents.", "contents": "Synergistic action of cyclic GMP on catecholamine-induced chloride current in guinea-pig ventricular cells. 1. Effects of cyclic GMP on the catecholamine-induced chloride current (ICl) were studied using the whole-cell patch-clamp technique combined with internal perfusion in single ventricular myocytes dispersed from guinea-pig heart. 2. When ICl was activated by submaximal doses of isoprenaline (0.01-0.1 microM), adrenaline (0.5-1 microM) and histamine (0.2-0.5 microM), intracellular dialysis with cyclic GMP (10-100 microM) induced an extra increase of ICl. No further increase of ICl was induced by cyclic GMP when ICl was maximally activated. In the absence of agonists, cyclic GMP failed to induce ICl. 3. The enhancement by cyclic GMP was also observed when ICl was activated by external application of 0.2-1.0 microM-forskolin or by internal dialysis with a pipette solution containing 50-200 microM-cyclic AMP. 4. In contrast to cyclic GMP, 10-1000 microM-dibutyryl cyclic GMP and 8-bromo-cyclic GMP were ineffective in modifying ICl. 5. Milrinone (1-10 microM), a specific inhibitor of a kind of phosphodiesterase which is inhibited by cyclic GMP, also enhanced ICl activated by submaximal doses of isoprenaline. Milrinone itself did not activate ICl. 6. When ICl was enhanced by 5 microM-milrinone, an additional application of cyclic GMP failed to increase ICl. In the presence of cyclic GMP, milrinone failed to enhance ICl. 7. The above findings on ICl are analogous to the enhancement by cyclic GMP of the beta-adrenergic stimulation of the Ca2+ current reported in the same preparation, and support the hypothesis that in mammalian cardiac cells cyclic GMP potentiates elevation of cyclic AMP induced by beta-adrenergic agents, and thereby increases the amplitudes of ionic currents."} {"id": "PMID:1281507", "title": "Three components in the light-induced current of the Limulus ventral photoreceptor.", "content": "1. Light-induced currents were measured in Limulus ventral nerve photoreceptors using a two-electrode voltage clamp. Three kinetically distinct components in the light-induced current could be distinguished by varying the light adaptation state of the photoreceptor and the intensity of the stimulus light. 2. The components could be partly separated by choosing appropriate stimulus intensities and dark adaptation time. Thus the properties of the components could be separately studied. The first component is the first to recover after a light adaptation, appears temporally first in the light-induced response, has the lowest activation threshold and is the smallest. The second component needs a longer time to recover after an adapting illumination and its kinetics differ from that of the other components. Applying a bright stimulus to a dark-adapted cell a third component can be observed late in the response. 3. The time to peak of the first and the third components depended on the stimulus intensity, but not on the dark adaptation time. The time to peak of the second component became shorter the longer the dark adaptation time. For a constant adaptation state the time to the maximum of component 2 was independent, but those of components 1 and 3 were dependent on the membrane voltage. 4. To exclude the possibility of the contribution of voltage-gated currents, light-activated currents were measured at clamp potentials more negative than -50 mV after adding 4-aminopyridine into the bath solution or injecting tetraethyl-ammonium chloride into the cell. The properties of the three components remained unchanged under these conditions. 5. The I-V curve of the first component was flat at negative membrane potentials and had a strong outward rectification at positive membrane potentials. The I-V curve of component 3 showed a negative resistance at potentials more negative than about -30 mV. In contrast, the I-V curve for the second component was always nearly linear. 6. No membrane potential was found where the light-induced current was zero. Instead, current traces close to the reversal potential showed a complex waveform indicating different reversal potentials for the three components. 7. The results indicate that the current components are caused by three different populations of light-sensitive channels. The different activations, deactivations and recovery kinetics of the components suggest that the three types of channels are activated by distinct intracellular transmitters.", "contents": "Three components in the light-induced current of the Limulus ventral photoreceptor. 1. Light-induced currents were measured in Limulus ventral nerve photoreceptors using a two-electrode voltage clamp. Three kinetically distinct components in the light-induced current could be distinguished by varying the light adaptation state of the photoreceptor and the intensity of the stimulus light. 2. The components could be partly separated by choosing appropriate stimulus intensities and dark adaptation time. Thus the properties of the components could be separately studied. The first component is the first to recover after a light adaptation, appears temporally first in the light-induced response, has the lowest activation threshold and is the smallest. The second component needs a longer time to recover after an adapting illumination and its kinetics differ from that of the other components. Applying a bright stimulus to a dark-adapted cell a third component can be observed late in the response. 3. The time to peak of the first and the third components depended on the stimulus intensity, but not on the dark adaptation time. The time to peak of the second component became shorter the longer the dark adaptation time. For a constant adaptation state the time to the maximum of component 2 was independent, but those of components 1 and 3 were dependent on the membrane voltage. 4. To exclude the possibility of the contribution of voltage-gated currents, light-activated currents were measured at clamp potentials more negative than -50 mV after adding 4-aminopyridine into the bath solution or injecting tetraethyl-ammonium chloride into the cell. The properties of the three components remained unchanged under these conditions. 5. The I-V curve of the first component was flat at negative membrane potentials and had a strong outward rectification at positive membrane potentials. The I-V curve of component 3 showed a negative resistance at potentials more negative than about -30 mV. In contrast, the I-V curve for the second component was always nearly linear. 6. No membrane potential was found where the light-induced current was zero. Instead, current traces close to the reversal potential showed a complex waveform indicating different reversal potentials for the three components. 7. The results indicate that the current components are caused by three different populations of light-sensitive channels. The different activations, deactivations and recovery kinetics of the components suggest that the three types of channels are activated by distinct intracellular transmitters."} {"id": "PMID:1281508", "title": "Antithyroid effects of coal-derived pollutants.", "content": "Endemic goiter in iodide-sufficient areas of the United States and Colombia has been linked to watersheds rich in coal and shale, which several reports suggest are the source of water-borne goitrogens. In this report the potential antithyroid activities of aqueous coal and shale extracts and of compounds identified in aqueous effluents from coal conversion processes were assayed in thyroid peroxidase (TPO) and thyroid slice systems. Aqueous extracts of coal and black shale were potent inhibitors of TPO or 125I organification by thyroid slices. The most abundant water-soluble compounds derived from coal are dihydroxy-phenols, thiocyanate, disulfides, and hydroxypyridines. The dihydroxyphenols resorcinol, 2-methylresorcinol, and 5-methylresorcinol (orcinol) were 26.7, 22.5, and 7.2 times more potent, respectively, than the antithyroid drug 6-propylthiouracil (PTU). Other dihydroxyphenols and thiocyanate were less potent but comparable in activity to PTU. All dihydroxypyridines and 3-hydroxypyridine produced inhibitory effects comparable to PTU. None of the disulfides inhibited TPO. The antiperoxidase effects of combinations of two dihydroxyphenols or one dihydroxyphenol and SCN were additive, whereas the effects of a combination of four dihydroxyphenols at threshold inhibitory concentrations were synergistic, resulting in net effects equivalent to or greater than the sum of the individual effects. Thus, antithyroid effects may be greatly amplified by exposure to multiple coal-derived goitrogens and could be many times that produced by any one of the contributing pollutants. These results demonstrate that potent water-borne goitrogens are derived from coal and shale and that their contamination of water supplies could pose a serious threat of thyroid disorders.", "contents": "Antithyroid effects of coal-derived pollutants. Endemic goiter in iodide-sufficient areas of the United States and Colombia has been linked to watersheds rich in coal and shale, which several reports suggest are the source of water-borne goitrogens. In this report the potential antithyroid activities of aqueous coal and shale extracts and of compounds identified in aqueous effluents from coal conversion processes were assayed in thyroid peroxidase (TPO) and thyroid slice systems. Aqueous extracts of coal and black shale were potent inhibitors of TPO or 125I organification by thyroid slices. The most abundant water-soluble compounds derived from coal are dihydroxy-phenols, thiocyanate, disulfides, and hydroxypyridines. The dihydroxyphenols resorcinol, 2-methylresorcinol, and 5-methylresorcinol (orcinol) were 26.7, 22.5, and 7.2 times more potent, respectively, than the antithyroid drug 6-propylthiouracil (PTU). Other dihydroxyphenols and thiocyanate were less potent but comparable in activity to PTU. All dihydroxypyridines and 3-hydroxypyridine produced inhibitory effects comparable to PTU. None of the disulfides inhibited TPO. The antiperoxidase effects of combinations of two dihydroxyphenols or one dihydroxyphenol and SCN were additive, whereas the effects of a combination of four dihydroxyphenols at threshold inhibitory concentrations were synergistic, resulting in net effects equivalent to or greater than the sum of the individual effects. Thus, antithyroid effects may be greatly amplified by exposure to multiple coal-derived goitrogens and could be many times that produced by any one of the contributing pollutants. These results demonstrate that potent water-borne goitrogens are derived from coal and shale and that their contamination of water supplies could pose a serious threat of thyroid disorders."} {"id": "PMID:1281509", "title": "Effect of inhaled dimethylselenide in the Fischer 344 male rat.", "content": "In this project, a total of 60 adult Fischer 344 male rats were exposed to dimethylselenide (DMSe) vapor at 1607, 4499, or 8034 ppm for 1 h (20 rats/group). In addition, 26 unexposed rats were used as controls. The exposed rats were observed frequently during the 7 d following exposure and appeared normal. The animals were sacrificed at either 1 or 7 d after inhalation and the major tissues were grossly examined and weighed. Selenium levels were found to be elevated only in the lung at d 1. At d 1, significant changes in organ weights were an increase in the lung weight at exposure levels of 1607 and 8034 ppm of DMSe and in liver weight at 4499 and 8034 ppm. At d 1, significant changes in the lung were an increase in protein at 1607 and 8034 ppm of DMSe, and an increase in RNA and a reduction in DNA at 4499 ppm DMSe. The only change in the liver was a reduction in DNA at 4499 ppm. At 7 d, the protein content and RNA content of spleen were increased. Lung, liver, kidney, spleen, thymus, lymph nodes, pancreas, and adrenal gland were examined microscopically and found to be normal. All of these observed responses were minor and did not severely impact the health of the rats. Overall, the data indicate that the inhalation of DMSe for 1 h has relatively low toxicity in rats even at high concentrations.", "contents": "Effect of inhaled dimethylselenide in the Fischer 344 male rat. In this project, a total of 60 adult Fischer 344 male rats were exposed to dimethylselenide (DMSe) vapor at 1607, 4499, or 8034 ppm for 1 h (20 rats/group). In addition, 26 unexposed rats were used as controls. The exposed rats were observed frequently during the 7 d following exposure and appeared normal. The animals were sacrificed at either 1 or 7 d after inhalation and the major tissues were grossly examined and weighed. Selenium levels were found to be elevated only in the lung at d 1. At d 1, significant changes in organ weights were an increase in the lung weight at exposure levels of 1607 and 8034 ppm of DMSe and in liver weight at 4499 and 8034 ppm. At d 1, significant changes in the lung were an increase in protein at 1607 and 8034 ppm of DMSe, and an increase in RNA and a reduction in DNA at 4499 ppm DMSe. The only change in the liver was a reduction in DNA at 4499 ppm. At 7 d, the protein content and RNA content of spleen were increased. Lung, liver, kidney, spleen, thymus, lymph nodes, pancreas, and adrenal gland were examined microscopically and found to be normal. All of these observed responses were minor and did not severely impact the health of the rats. Overall, the data indicate that the inhalation of DMSe for 1 h has relatively low toxicity in rats even at high concentrations."} {"id": "PMID:1281510", "title": "Treatment of intra-abdominal infection with granulocyte colony-stimulating factor.", "content": "Polymicrobial infection is a significant cause of mortality in critically ill patients. Antibiotics and surgical intervention are useful but limited in their effectiveness for combating mixed infections. New prophylactic and therapeutic approaches are required to improve survival in critically ill patients. Neutrophils are a known primary host defense mechanism against bacterial infection. We evaluated the use of a neutrophil growth factor, recombinant human granulocyte colony-stimulating factor (G-CSF), to improve survival in a well-established sepsis model, cecal ligation and puncture (CLP). When administered beginning 4 days before CLP with injections continuing for 14 days after CLP, mice that received 10, 100, or 1000 ng of G-CSF had significantly improved survival compared with the control group. When treatment began at the time of CLP and continued for 7 days after CLP, G-CSF treatment resulted in a dose-dependent improvement in survival in groups that received 100, 500, or 1000 ng. The interaction of G-CSF and conventional antimicrobial therapy was evaluated by administration of G-CSF plus gentamicin. Mice received 100 ng of G-CSF beginning on day 1 before CLP with injections continuing for 3 days after CLP. Gentamicin-treated mice received a single 15 mg/kg injection of gentamicin at the time of CLP. Mice that received G-CSF alone or gentamicin alone had significantly improved survival compared with controls. Mice that received G-CSF plus gentamicin had improved survival compared with control mice and compared with mice that received G-CSF alone but not compared with mice that received gentamicin alone.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Treatment of intra-abdominal infection with granulocyte colony-stimulating factor. Polymicrobial infection is a significant cause of mortality in critically ill patients. Antibiotics and surgical intervention are useful but limited in their effectiveness for combating mixed infections. New prophylactic and therapeutic approaches are required to improve survival in critically ill patients. Neutrophils are a known primary host defense mechanism against bacterial infection. We evaluated the use of a neutrophil growth factor, recombinant human granulocyte colony-stimulating factor (G-CSF), to improve survival in a well-established sepsis model, cecal ligation and puncture (CLP). When administered beginning 4 days before CLP with injections continuing for 14 days after CLP, mice that received 10, 100, or 1000 ng of G-CSF had significantly improved survival compared with the control group. When treatment began at the time of CLP and continued for 7 days after CLP, G-CSF treatment resulted in a dose-dependent improvement in survival in groups that received 100, 500, or 1000 ng. The interaction of G-CSF and conventional antimicrobial therapy was evaluated by administration of G-CSF plus gentamicin. Mice received 100 ng of G-CSF beginning on day 1 before CLP with injections continuing for 3 days after CLP. Gentamicin-treated mice received a single 15 mg/kg injection of gentamicin at the time of CLP. Mice that received G-CSF alone or gentamicin alone had significantly improved survival compared with controls. Mice that received G-CSF plus gentamicin had improved survival compared with control mice and compared with mice that received G-CSF alone but not compared with mice that received gentamicin alone.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281511", "title": "[Neurobiology of physical environmental stress].", "content": "Although effects of physical environmental stress, including noise and whole-body vibration, on human psychological activities and emotion are not negligible for environmental and occupational hygiene, attempts to elucidate their physiological and biomedical mechanisms have been not made until recently. Neurobiological researches on the effects of the physical environment, e.g., noise and whole-body vibration on organisms were reviewed. It has been well accepted that such effects can be classified into specific and nonspecific reactions to the stressor. Activations of the mesofrontal and the meso-accumbens dopaminergic (DA) systems and changes of frontal substance P (SP) have been reported to play a part in emotional changes and to be induced by acute physical environmental stressors as a nonspecific reaction. On the basis of data demonstrating that these three systems do not show the same changes with the chronic exposure, it is assumed that emotional changes may account for the differences among the systems. Specific responses of amygdaline DA and SP to noise suggest that the psychopharmacological mechanisms by which actions of DA and SP in the cortical association areas for the sensory systems of hearing, as well as in the amygdala and the mesencephalon together, cause the specific sensation of noise, and furthermore lead to psychological and physical nonspecific reactions. In these mechanisms, descending amygdalofugal neural systems of SP, neurotensin (NT) and somatostatin are activated as a common pathway, and subsequently relayed to the hypothalamus-pituitary system responsible for several endocrinological hormones. The involvements of the hippocampal VIP in whole-body vibration and of the DA and NT in cold exposure have been pointed out. Further researches to elucidate the roles of central neurotransmitters in physical environmental stress will be important in the study of human high-level mental activity.", "contents": "[Neurobiology of physical environmental stress]. Although effects of physical environmental stress, including noise and whole-body vibration, on human psychological activities and emotion are not negligible for environmental and occupational hygiene, attempts to elucidate their physiological and biomedical mechanisms have been not made until recently. Neurobiological researches on the effects of the physical environment, e.g., noise and whole-body vibration on organisms were reviewed. It has been well accepted that such effects can be classified into specific and nonspecific reactions to the stressor. Activations of the mesofrontal and the meso-accumbens dopaminergic (DA) systems and changes of frontal substance P (SP) have been reported to play a part in emotional changes and to be induced by acute physical environmental stressors as a nonspecific reaction. On the basis of data demonstrating that these three systems do not show the same changes with the chronic exposure, it is assumed that emotional changes may account for the differences among the systems. Specific responses of amygdaline DA and SP to noise suggest that the psychopharmacological mechanisms by which actions of DA and SP in the cortical association areas for the sensory systems of hearing, as well as in the amygdala and the mesencephalon together, cause the specific sensation of noise, and furthermore lead to psychological and physical nonspecific reactions. In these mechanisms, descending amygdalofugal neural systems of SP, neurotensin (NT) and somatostatin are activated as a common pathway, and subsequently relayed to the hypothalamus-pituitary system responsible for several endocrinological hormones. The involvements of the hippocampal VIP in whole-body vibration and of the DA and NT in cold exposure have been pointed out. Further researches to elucidate the roles of central neurotransmitters in physical environmental stress will be important in the study of human high-level mental activity."} {"id": "PMID:1281512", "title": "Immunohistochemical studies of Merkel cell carcinoma of the eyelid.", "content": "Merkel cell carcinoma of the eyelid is a rare malignant tumor. Immunohistochemical studies can be helpful in establishing the diagnosis of this tumor. We encountered a case of Merkel cell carcinoma of the eyelid and conducted an immunohistochemical analysis for clarification of its cell properties. The patient in this study was a 78-year-old man who noted a small mass on his right upper eyelid, which was subsequently removed. However, the lesion recurred and progressively enlarged. The results of a biopsy indicated the possibility of a highly malignant tumor. The lesion was removed by orbital exenteration. Merkel cell carcinoma was finally diagnosed by using light and electron microscopy. In immunohistochemical studies, the tumor cells showed both neuron-specific enolase and cytokeratin. Most of the cells were also labeled with antibodies against the protein gene product 9.5, endocrine granule constituent and chromogranin A. However, no neuropeptides were labeled. The properties of the tumor cells appeared virtually the same as those of normal human Merkel cells.", "contents": "Immunohistochemical studies of Merkel cell carcinoma of the eyelid. Merkel cell carcinoma of the eyelid is a rare malignant tumor. Immunohistochemical studies can be helpful in establishing the diagnosis of this tumor. We encountered a case of Merkel cell carcinoma of the eyelid and conducted an immunohistochemical analysis for clarification of its cell properties. The patient in this study was a 78-year-old man who noted a small mass on his right upper eyelid, which was subsequently removed. However, the lesion recurred and progressively enlarged. The results of a biopsy indicated the possibility of a highly malignant tumor. The lesion was removed by orbital exenteration. Merkel cell carcinoma was finally diagnosed by using light and electron microscopy. In immunohistochemical studies, the tumor cells showed both neuron-specific enolase and cytokeratin. Most of the cells were also labeled with antibodies against the protein gene product 9.5, endocrine granule constituent and chromogranin A. However, no neuropeptides were labeled. The properties of the tumor cells appeared virtually the same as those of normal human Merkel cells."} {"id": "PMID:1281513", "title": "Tubular metabolism of aprotinin 99mTc and urinary ammonia: effects of proteinuria.", "content": "Increased renal ammoniagenesis is pathogenic in animals. Thus, tubular degradation of filtered proteins to ammonia might link proteinuria to disease progression. The tubular uptake, metabolism and fractional degradation of aprotinin 99mTc (Trasylol), were measured in 26 glomerulonephritic patients with normal renal function, 10 with proteinuria > 5 g/24 h. In addition, urinary ammonia pH, and titratable acidity were measured. Patients with heavy proteinuria had a higher tubular metabolism, a lower uptake and a higher fractional degradation of aprotinin. Urinary ammonia and titratable acidity were also increased. Fractional degradation and urinary ammonia were strongly correlated as were urinary ammonia and proteinuria.", "contents": "Tubular metabolism of aprotinin 99mTc and urinary ammonia: effects of proteinuria. Increased renal ammoniagenesis is pathogenic in animals. Thus, tubular degradation of filtered proteins to ammonia might link proteinuria to disease progression. The tubular uptake, metabolism and fractional degradation of aprotinin 99mTc (Trasylol), were measured in 26 glomerulonephritic patients with normal renal function, 10 with proteinuria > 5 g/24 h. In addition, urinary ammonia pH, and titratable acidity were measured. Patients with heavy proteinuria had a higher tubular metabolism, a lower uptake and a higher fractional degradation of aprotinin. Urinary ammonia and titratable acidity were also increased. Fractional degradation and urinary ammonia were strongly correlated as were urinary ammonia and proteinuria."} {"id": "PMID:1281514", "title": "Regulated inactivation of homologous gene expression in transgenic Nicotiana sylvestris plants containing a defense-related tobacco chitinase gene.", "content": "The class I chitinases are vacuolar proteins implicated in the defense of plants against pathogens. Leaves of transgenic Nicotiana sylvestris plants homozygous for a chimeric tobacco (Nicotiana tabacum) chitinase gene with Cauliflower Mosaic Virus (CaMV) 35S RNA expression signals usually accumulate high levels of chitinase relative to comparable leaves of non-transformed plants. Unexpectedly, some transgenic plants accumulated lower levels of chitinase than nontransformed plants. We call this phenomenon silencing. The incidence of silencing depends on the early rearing conditions of the plants. When grown to maturity in a greenhouse, approximately 25% of plants raised as seedlings in closed culture vessels were of the silent type; none of the plants raised from seed in a greenhouse showed this phenotype. Silencing is also developmentally regulated. Plants showed three patterns of chitinase expression: uniformly high levels of expression in different leaves, uniformly low levels of expression in different leaves, and position-dependent silencing in which expression was uniform within individual leaves but varied in different leaves on the same plant. Heritability of the silent phenotype was examined in plants homozygous for the transgene. Some direct descendants exhibited a high-silent-high sequence of activity phenotypes in successive sexual generations, which cannot be explained by simple Mendelian inheritance. Taken together, the results indicate that silencing results from stable but potentially reversible states of gene expression that are not meiotically transmitted. Gene-specific measurements of chitinase and chitinase mRNA showed that silencing results from co-suppression, i.e. the inactivation of both host and transgene expression in trans. The silent state was not correlated with cytosine methylation of the transgene at the five restriction sites investigated.", "contents": "Regulated inactivation of homologous gene expression in transgenic Nicotiana sylvestris plants containing a defense-related tobacco chitinase gene. The class I chitinases are vacuolar proteins implicated in the defense of plants against pathogens. Leaves of transgenic Nicotiana sylvestris plants homozygous for a chimeric tobacco (Nicotiana tabacum) chitinase gene with Cauliflower Mosaic Virus (CaMV) 35S RNA expression signals usually accumulate high levels of chitinase relative to comparable leaves of non-transformed plants. Unexpectedly, some transgenic plants accumulated lower levels of chitinase than nontransformed plants. We call this phenomenon silencing. The incidence of silencing depends on the early rearing conditions of the plants. When grown to maturity in a greenhouse, approximately 25% of plants raised as seedlings in closed culture vessels were of the silent type; none of the plants raised from seed in a greenhouse showed this phenotype. Silencing is also developmentally regulated. Plants showed three patterns of chitinase expression: uniformly high levels of expression in different leaves, uniformly low levels of expression in different leaves, and position-dependent silencing in which expression was uniform within individual leaves but varied in different leaves on the same plant. Heritability of the silent phenotype was examined in plants homozygous for the transgene. Some direct descendants exhibited a high-silent-high sequence of activity phenotypes in successive sexual generations, which cannot be explained by simple Mendelian inheritance. Taken together, the results indicate that silencing results from stable but potentially reversible states of gene expression that are not meiotically transmitted. Gene-specific measurements of chitinase and chitinase mRNA showed that silencing results from co-suppression, i.e. the inactivation of both host and transgene expression in trans. The silent state was not correlated with cytosine methylation of the transgene at the five restriction sites investigated."} {"id": "PMID:1281515", "title": "Sequence and transcript analysis of the Nco2.5 Ogura-specific fragment correlated with cytoplasmic male sterility in Brassica cybrids.", "content": "Sequence analysis of the Ogura-specific mitochondrial DNA (mtDNA) fragment isolated previously from Brassica cybrids carrying Ogura cytoplasmic male sterility (cms) revealed a tRNA(fMet) sequence, a putative 138 amino acid open reading frame (orf138), and a 158 amino acid ORF (orf158) previously observed in mitochondrial genomes from several other plant species. Transcription mapping showed that both ORFs are present on a 1.4 kb cms-specific transcript. The orf158 sequence is also transcribed in fertile plants on a different mRNA, and thus is unlikely to be related to cms. On the other hand, fertile revertant plants lack transcripts of the orf138 sequence, whose possible role in the mechanism of Ogura cms is discussed.", "contents": "Sequence and transcript analysis of the Nco2.5 Ogura-specific fragment correlated with cytoplasmic male sterility in Brassica cybrids. Sequence analysis of the Ogura-specific mitochondrial DNA (mtDNA) fragment isolated previously from Brassica cybrids carrying Ogura cytoplasmic male sterility (cms) revealed a tRNA(fMet) sequence, a putative 138 amino acid open reading frame (orf138), and a 158 amino acid ORF (orf158) previously observed in mitochondrial genomes from several other plant species. Transcription mapping showed that both ORFs are present on a 1.4 kb cms-specific transcript. The orf158 sequence is also transcribed in fertile plants on a different mRNA, and thus is unlikely to be related to cms. On the other hand, fertile revertant plants lack transcripts of the orf138 sequence, whose possible role in the mechanism of Ogura cms is discussed."} {"id": "PMID:1281516", "title": "Transcriptional analysis of the fix ABCXORF1 region of Azorhizobium caulinodans suggests post-transcriptional processing of the fix ABCXORF1 mRNA.", "content": "We report here the transcriptional analysis of the fixABCXORF1 region of Azorhizobium caulinodans. This led to the identification of a 0.9 kb transcript covering fixX and ORF1, which was synthesized only under conditions of nitrogen fixation. The 5' end of this transcript was mapped by primer extension and S1 nuclease protection analyses and shown to be located 70 +/- 1 nucleotides upstream of the fixX start codon. By means of transcriptional fixX- and ORF1-lacZ fusions, it was shown that fixX and ORF1 were most probably transcribed from the fixA promoter and that expression of fixX and ORF1 was dependent on NifA activation. This suggests that the 0.9 kb mRNA results from post-transcriptional processing of a large mRNA covering fixA,B,C,X and ORF1. In addition, ORF1 mutants were constructed and were shown not to be impaired in nitrogenase activity.", "contents": "Transcriptional analysis of the fix ABCXORF1 region of Azorhizobium caulinodans suggests post-transcriptional processing of the fix ABCXORF1 mRNA. We report here the transcriptional analysis of the fixABCXORF1 region of Azorhizobium caulinodans. This led to the identification of a 0.9 kb transcript covering fixX and ORF1, which was synthesized only under conditions of nitrogen fixation. The 5' end of this transcript was mapped by primer extension and S1 nuclease protection analyses and shown to be located 70 +/- 1 nucleotides upstream of the fixX start codon. By means of transcriptional fixX- and ORF1-lacZ fusions, it was shown that fixX and ORF1 were most probably transcribed from the fixA promoter and that expression of fixX and ORF1 was dependent on NifA activation. This suggests that the 0.9 kb mRNA results from post-transcriptional processing of a large mRNA covering fixA,B,C,X and ORF1. In addition, ORF1 mutants were constructed and were shown not to be impaired in nitrogenase activity."} {"id": "PMID:1281517", "title": "Two non-gypsy rudimentary mutations and their suppression by mutations of suppressor of Hairy-wing in Drosophila.", "content": "Two spontaneous mutations of rudimentary, the gene encoding the first steps of de novo pyrimidine biosynthesis in Drosophila, are suppressed by mutant alleles of the suppressor of Hairy-wing locus. This interaction differs from typical su(Hw) suppression in that neither rudimentary allele is associated with an insertion of the gypsy retrotransposon. One allele, rsP1, appears to be a point mutation. Adult rsP1 homozygous females accumulate substantially less 7.3 kb rudimentary transcript than do wild-type females. The other allele, rsP2, is an insertion of an mdg3 retrotransposon in the sixth exon of rudimentary and in the opposite transcriptional orientation. This insertion divides the rudimentary locus into two separate, yet functional, transcription units by truncating transcription from the rudimentary promoter and promoting transcription of downstream rudimentary sequences. Phenotypic suppression of both rsP1 and rsP2 by mutant alleles of the suppressor of Hairy-wing locus correlates with enhanced levels of the rsP1 and rsP2 transcripts.", "contents": "Two non-gypsy rudimentary mutations and their suppression by mutations of suppressor of Hairy-wing in Drosophila. Two spontaneous mutations of rudimentary, the gene encoding the first steps of de novo pyrimidine biosynthesis in Drosophila, are suppressed by mutant alleles of the suppressor of Hairy-wing locus. This interaction differs from typical su(Hw) suppression in that neither rudimentary allele is associated with an insertion of the gypsy retrotransposon. One allele, rsP1, appears to be a point mutation. Adult rsP1 homozygous females accumulate substantially less 7.3 kb rudimentary transcript than do wild-type females. The other allele, rsP2, is an insertion of an mdg3 retrotransposon in the sixth exon of rudimentary and in the opposite transcriptional orientation. This insertion divides the rudimentary locus into two separate, yet functional, transcription units by truncating transcription from the rudimentary promoter and promoting transcription of downstream rudimentary sequences. Phenotypic suppression of both rsP1 and rsP2 by mutant alleles of the suppressor of Hairy-wing locus correlates with enhanced levels of the rsP1 and rsP2 transcripts."} {"id": "PMID:1281518", "title": "Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from alpha-factor arrest in yeast.", "content": "The structurally unrelated immunosuppressants FK506 and cyclosporin A (CsA) act similarly, inhibiting a Ca(2+)-dependent signal required for interleukin-2 transcription and T-cell activation. Each drug binds to its cytosolic receptor, FKBP-12 and cyclophilin, respectively, and the drug-receptor complexes inhibit the Ca2+/calmodulin-dependent protein phosphatase, calcineurin. In yeast, calcineurin has been implicated in recovery from alpha-mating factor arrest. Here we show that FK506 bound to yeast FKBP-12 appears to form a complex with yeast calcineurin. Moreover, recovery from mating factor arrest is highly sensitive to FK506 or CsA, and this sensitivity requires the presence of FKBP-12 or cyclophilin, respectively. These results define a key physiological target of an FK506- and CsA-sensitive signal pathway in yeast, suggest a high degree of mechanistic conservation with mammalian cells, and indicate that further examination of the yeast system should provide insight into the same process in T cells.", "contents": "Calcineurin mediates inhibition by FK506 and cyclosporin of recovery from alpha-factor arrest in yeast. The structurally unrelated immunosuppressants FK506 and cyclosporin A (CsA) act similarly, inhibiting a Ca(2+)-dependent signal required for interleukin-2 transcription and T-cell activation. Each drug binds to its cytosolic receptor, FKBP-12 and cyclophilin, respectively, and the drug-receptor complexes inhibit the Ca2+/calmodulin-dependent protein phosphatase, calcineurin. In yeast, calcineurin has been implicated in recovery from alpha-mating factor arrest. Here we show that FK506 bound to yeast FKBP-12 appears to form a complex with yeast calcineurin. Moreover, recovery from mating factor arrest is highly sensitive to FK506 or CsA, and this sensitivity requires the presence of FKBP-12 or cyclophilin, respectively. These results define a key physiological target of an FK506- and CsA-sensitive signal pathway in yeast, suggest a high degree of mechanistic conservation with mammalian cells, and indicate that further examination of the yeast system should provide insight into the same process in T cells."} {"id": "PMID:1281521", "title": "Evidence for a role of the neuropeptide galanin in spatial learning.", "content": "The neuropeptide galanin coexists with acetylcholine (ACh) in the basal forebrain cholinergic neurons and modulates cholinergic activity in the forebrain. The cholinergic forebrain neurons appear to play a significant role in learning and memory, as suggested by a severe loss of these neurons in Alzheimer's disease. The involvement of endogenous galanin in learning is demonstrated here by the use of the recently synthesized high-affinity galanin antagonist M35 [galanin(1-13)-bradykinin(2-9) amide] (Kd = 0.1 nM). Intracerebroventricular (i.c.v.) administration of M35 (6 but not 3 nmol) produced a significant (P < 0.025) facilitation of acquisition in a spatial learning test (Morris swim maze) without any increase in swim speed. Thus, M35 (6 nmol) shortened the escape latency, reduced the number of failures to reach the platform, and shortened the path length to reach the hidden platform. M35 (3 and 6 nmol) tended to enhance retention performance seven days after the last training session. Receptor autoradiographic studies on the distribution of [125I]M35 following i.c.v. administration show that it binds preferentially in the periventricular regions including the hippocampus. These results suggest that galanin may modulate spatial learning and memory and that galanin antagonists may provide a new principle in the treatment of Alzheimer's disease.", "contents": "Evidence for a role of the neuropeptide galanin in spatial learning. The neuropeptide galanin coexists with acetylcholine (ACh) in the basal forebrain cholinergic neurons and modulates cholinergic activity in the forebrain. The cholinergic forebrain neurons appear to play a significant role in learning and memory, as suggested by a severe loss of these neurons in Alzheimer's disease. The involvement of endogenous galanin in learning is demonstrated here by the use of the recently synthesized high-affinity galanin antagonist M35 [galanin(1-13)-bradykinin(2-9) amide] (Kd = 0.1 nM). Intracerebroventricular (i.c.v.) administration of M35 (6 but not 3 nmol) produced a significant (P < 0.025) facilitation of acquisition in a spatial learning test (Morris swim maze) without any increase in swim speed. Thus, M35 (6 nmol) shortened the escape latency, reduced the number of failures to reach the platform, and shortened the path length to reach the hidden platform. M35 (3 and 6 nmol) tended to enhance retention performance seven days after the last training session. Receptor autoradiographic studies on the distribution of [125I]M35 following i.c.v. administration show that it binds preferentially in the periventricular regions including the hippocampus. These results suggest that galanin may modulate spatial learning and memory and that galanin antagonists may provide a new principle in the treatment of Alzheimer's disease."} {"id": "PMID:1281519", "title": "Formation of haematopoietic microenvironment and haematopoietic stem cells from single human bone marrow stem cells.", "content": "Haematopoietic stem cells are a population of cells capable both of self renewal and of differentiation into a variety of haematopoietic lineages. Enrichment techniques of human haematopoietic stem cells have used the expression of CD34, present on bone marrow progenitor cells. But most CD34+ bone marrow cells are committed to their lineage, and more recent efforts have focused on the precise characterization of the pluripotent subset of CD34+ cells. Here we report the characterization of two distinct subsets of pluripotent stem cells from human fetal bone marrow, a CD34+, HLA-DR+, CD38- subset that can differentiate into all haematopoietic lineages, and a distinct more primitive subset, that is CD34+, HLA-DR-, CD38-, that can differentiate into haematopoietic precursors and stromal cells capable of supporting the differentiation of these precursors. These data represent, to our knowledge, the first identification of a single cell capable of reconstituting the haematopoietic cells and their associated bone marrow microenvironment.", "contents": "Formation of haematopoietic microenvironment and haematopoietic stem cells from single human bone marrow stem cells. Haematopoietic stem cells are a population of cells capable both of self renewal and of differentiation into a variety of haematopoietic lineages. Enrichment techniques of human haematopoietic stem cells have used the expression of CD34, present on bone marrow progenitor cells. But most CD34+ bone marrow cells are committed to their lineage, and more recent efforts have focused on the precise characterization of the pluripotent subset of CD34+ cells. Here we report the characterization of two distinct subsets of pluripotent stem cells from human fetal bone marrow, a CD34+, HLA-DR+, CD38- subset that can differentiate into all haematopoietic lineages, and a distinct more primitive subset, that is CD34+, HLA-DR-, CD38-, that can differentiate into haematopoietic precursors and stromal cells capable of supporting the differentiation of these precursors. These data represent, to our knowledge, the first identification of a single cell capable of reconstituting the haematopoietic cells and their associated bone marrow microenvironment."} {"id": "PMID:1281522", "title": "Comparative distribution of neurokinin B-, substance P- and enkephalin-like immunoreactivities and neurokinin B messenger RNA in the basal forebrain of the rat: evidence for neurochemical compartmentation.", "content": "The distribution of neurokinin B was investigated in the basal forebrain of the rat by immunocytochemistry with an antibody directed against neurokinin B, and with a second antiserum directed to a peptide sequence contained within its precursor, and by means of in situ hybridization. The staining pattern was compared in closely adjacent sections to that of substance P- and enkephalin-like immunoreactivities. Cholecystokinin immunoreactivity was used to delineate the apparent dorsolateral border of the ventral pallidum with the nucleus accumbens. Remarkable similarities are found in the distribution of these peptides in the basal forebrain, especially in its ventral part. The coarse band-like terminal staining pattern (woolly fibers) that has been shown by others for substance P- and enkephalin-like immunoreactivity, is also observed for neurokinin B-like immunoreactivity, mainly in the ventral pallidum. Medium-sized cells are found arranged in clusters or singularly within the caudate-putamen even without colchicine. A band of strong neurokinin B immunoreactivity extends just underneath the dorsal pallidum to the amygdala. In comparison to enkephalin the most distinct observation is that neurokinin B immunoreactivity is not present in the dorsal pallidum (global pallidus). Neurokinin B immunoreactivity was not found in the pars reticulata of the substantia nigra which is strongly immunopositive for substance P. The number of cells detected by in situ hybridization was higher compared to the immunopositive perikarya throughout the basal ganglia. The staining pattern observed reflects a partial overlap with the substance P and enkephalin system although a differential distribution for each of these peptides was observed for cell bodies and axons terminals.", "contents": "Comparative distribution of neurokinin B-, substance P- and enkephalin-like immunoreactivities and neurokinin B messenger RNA in the basal forebrain of the rat: evidence for neurochemical compartmentation. The distribution of neurokinin B was investigated in the basal forebrain of the rat by immunocytochemistry with an antibody directed against neurokinin B, and with a second antiserum directed to a peptide sequence contained within its precursor, and by means of in situ hybridization. The staining pattern was compared in closely adjacent sections to that of substance P- and enkephalin-like immunoreactivities. Cholecystokinin immunoreactivity was used to delineate the apparent dorsolateral border of the ventral pallidum with the nucleus accumbens. Remarkable similarities are found in the distribution of these peptides in the basal forebrain, especially in its ventral part. The coarse band-like terminal staining pattern (woolly fibers) that has been shown by others for substance P- and enkephalin-like immunoreactivity, is also observed for neurokinin B-like immunoreactivity, mainly in the ventral pallidum. Medium-sized cells are found arranged in clusters or singularly within the caudate-putamen even without colchicine. A band of strong neurokinin B immunoreactivity extends just underneath the dorsal pallidum to the amygdala. In comparison to enkephalin the most distinct observation is that neurokinin B immunoreactivity is not present in the dorsal pallidum (global pallidus). Neurokinin B immunoreactivity was not found in the pars reticulata of the substantia nigra which is strongly immunopositive for substance P. The number of cells detected by in situ hybridization was higher compared to the immunopositive perikarya throughout the basal ganglia. The staining pattern observed reflects a partial overlap with the substance P and enkephalin system although a differential distribution for each of these peptides was observed for cell bodies and axons terminals."} {"id": "PMID:1281520", "title": "Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death.", "content": "Current ideas about the dependence of neurons on target-derived growth factors were formulated on the basis of experiments involving neurons with projections to the periphery. Nerve growth factor (NGF) and recently identified members of the NGF family of neuronal growth factors, known as neurotrophins, are thought to regulate survival of sympathetic and certain populations of sensory ganglion cells during development. Far less is known about factors that regulate the survival of spinal and cranial motor neurons, which also project to peripheral targets. NGF has not been shown to influence motor neuron survival, and whether the newly identified neurotrophins promote motor neuron survival is unknown. We show here that brain-derived neurotrophic factor (BDNF) is retrogradely transported by motor neurons in neonatal rats and that local application of BDNF to transected sciatic nerve prevents the massive death of motor neurons that normally follows axotomy in the neonatal period. These results show that BDNF has survival-promoting effects on motor neurons in vivo and suggest that BDNF may influence motor neuron survival during development.", "contents": "Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death. Current ideas about the dependence of neurons on target-derived growth factors were formulated on the basis of experiments involving neurons with projections to the periphery. Nerve growth factor (NGF) and recently identified members of the NGF family of neuronal growth factors, known as neurotrophins, are thought to regulate survival of sympathetic and certain populations of sensory ganglion cells during development. Far less is known about factors that regulate the survival of spinal and cranial motor neurons, which also project to peripheral targets. NGF has not been shown to influence motor neuron survival, and whether the newly identified neurotrophins promote motor neuron survival is unknown. We show here that brain-derived neurotrophic factor (BDNF) is retrogradely transported by motor neurons in neonatal rats and that local application of BDNF to transected sciatic nerve prevents the massive death of motor neurons that normally follows axotomy in the neonatal period. These results show that BDNF has survival-promoting effects on motor neurons in vivo and suggest that BDNF may influence motor neuron survival during development."} {"id": "PMID:1281523", "title": "Excitotoxic lesions of rat basal forebrain: differential effects on choline acetyltransferase in the cortex and amygdala.", "content": "Previous studies have shown that basal forebrain lesions using different excitotoxins produce similar decreases in cortical choline acetyltransferase, but differential effects on memory. However, basal forebrain cholinergic neurons send efferents to the amygdala and cortex. The present studies compared the effects of several excitotoxins on choline acetyltransferase levels in both of these structures. Lesions of the basal forebrain were made in rats by infusing different doses of either alpha-amine-3-hydroxy-5-methyl-4-isoxazole propionic acid, ibotenic acid, quisqualic acid, quinolinic acid or N-methyl-D-aspartic acid and measuring choline acetyltransferase seven days later. All of the excitotoxins exerted a differential response on cholinergic neurons of the basal forebrain projecting to the cortex or amygdala. Quinolinic acid was a more potent neurotoxin to cholinergic neurons innervating the amygdala than those projecting to the cortex. In contrast, quisqualic acid and alpha-amine-3-hydroxy-5-methyl-4-isoxazole were more potent neurotoxins to the cortical projection. alpha-Amine-3-hydroxy-5-methyl-4-isoxazole propionic acid was the most potent excitotoxin for destroying cholinergic neurons innervating either the cortex or amygdala. A parallel neurotoxic response was obtained in the cortex and amygdala following infusion of ibotenic acid or N-methyl-D-aspartic acid with little selectivity for choline acetyltransferase depletion in the cortex or amygdala. Histological analysis of the injection site revealed that acetylcholinesterase-positive neurons were destroyed by the excitotoxins in a dose-dependent manner. Excitotoxins (ibotenic acid, quinolinic acid, N-methyl-D-aspartic acid) that produce the greatest impairments in memory were found to produce the greatest depletion of choline acetyltransferase in the amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Excitotoxic lesions of rat basal forebrain: differential effects on choline acetyltransferase in the cortex and amygdala. Previous studies have shown that basal forebrain lesions using different excitotoxins produce similar decreases in cortical choline acetyltransferase, but differential effects on memory. However, basal forebrain cholinergic neurons send efferents to the amygdala and cortex. The present studies compared the effects of several excitotoxins on choline acetyltransferase levels in both of these structures. Lesions of the basal forebrain were made in rats by infusing different doses of either alpha-amine-3-hydroxy-5-methyl-4-isoxazole propionic acid, ibotenic acid, quisqualic acid, quinolinic acid or N-methyl-D-aspartic acid and measuring choline acetyltransferase seven days later. All of the excitotoxins exerted a differential response on cholinergic neurons of the basal forebrain projecting to the cortex or amygdala. Quinolinic acid was a more potent neurotoxin to cholinergic neurons innervating the amygdala than those projecting to the cortex. In contrast, quisqualic acid and alpha-amine-3-hydroxy-5-methyl-4-isoxazole were more potent neurotoxins to the cortical projection. alpha-Amine-3-hydroxy-5-methyl-4-isoxazole propionic acid was the most potent excitotoxin for destroying cholinergic neurons innervating either the cortex or amygdala. A parallel neurotoxic response was obtained in the cortex and amygdala following infusion of ibotenic acid or N-methyl-D-aspartic acid with little selectivity for choline acetyltransferase depletion in the cortex or amygdala. Histological analysis of the injection site revealed that acetylcholinesterase-positive neurons were destroyed by the excitotoxins in a dose-dependent manner. Excitotoxins (ibotenic acid, quinolinic acid, N-methyl-D-aspartic acid) that produce the greatest impairments in memory were found to produce the greatest depletion of choline acetyltransferase in the amygdala.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281524", "title": "Immunohistochemical localization of enkephalin and substance P in the nucleus caudalis of the spinal trigeminal V in the medulla oblongata of the human fetus.", "content": "The distribution of enkephalin-positive neurons, substance P-positive and enkephalin-positive fibers was studied in the nucleus caudalis of the trigeminal spinal V in the medulla oblongata regions of developing humans (12 weeks gestation to 40 weeks gestation). Enkephalin-positive neurons were identified in all the subnuclei of the nucleus caudalis as early as 12 weeks of gestation and increased in number as the fetus aged. Substance P-positive neurons were absent in this area throughout development. On the other hand, substance P-positive and enkephalin-positive fibers were present in all the subnuclei, again commencing as early as 12 weeks of gestation. These fibers tended to be linked to each other in the different subnuclei and to the reticular formation in this area and to increase significantly in quantity by the latter quarter of pregnancy. These results show the early presence of these neurons and fibers in the first trimester of development.", "contents": "Immunohistochemical localization of enkephalin and substance P in the nucleus caudalis of the spinal trigeminal V in the medulla oblongata of the human fetus. The distribution of enkephalin-positive neurons, substance P-positive and enkephalin-positive fibers was studied in the nucleus caudalis of the trigeminal spinal V in the medulla oblongata regions of developing humans (12 weeks gestation to 40 weeks gestation). Enkephalin-positive neurons were identified in all the subnuclei of the nucleus caudalis as early as 12 weeks of gestation and increased in number as the fetus aged. Substance P-positive neurons were absent in this area throughout development. On the other hand, substance P-positive and enkephalin-positive fibers were present in all the subnuclei, again commencing as early as 12 weeks of gestation. These fibers tended to be linked to each other in the different subnuclei and to the reticular formation in this area and to increase significantly in quantity by the latter quarter of pregnancy. These results show the early presence of these neurons and fibers in the first trimester of development."} {"id": "PMID:1281525", "title": "Neonatal sciatic nerve section results in thiamine monophosphate but not substance P or calcitonin gene-related peptide depletion from the terminal field in the dorsal horn of the rat: the role of collateral sprouting.", "content": "The expression of substance P, calcitonin gene-related peptide (CGRP) and thiamine monophosphatase in the sciatic nerve terminal field of the lumbar dorsal horn of the rat was examined following neonatal sciatic nerve section and ligation. The total terminal field from L3 to L5 was mapped from semi-serial sections on the treated side and compared to equivalent maps on the contralateral intact side. To obtain a detailed time course of events, data were obtained 4, 7, 10, 15-20 and 40-60 days after sciatic nerve section. At 4-7 days thiamine monophosphate was depleted from the cut nerve terminals resulting in a gap in dorsal horn thiamine monophosphate stain similar to that seen after adult nerve section. In contrast, substance P and CGRP-containing terminals showed only a transient fall in expression in the first week following nerve section and then staining was no different from that seen on the control side. The depletion of peptides normally observed after adult nerve section did not occur. This phenomenon was only observed if the sciatic nerve was cut at birth. Nerve section at 10 days of age resulted in the same pattern of peptide depletion as is observed in the adult. A week after neonatal sciatic nerve section, thiamine monophosphate-containing nerve terminals from nearby intact nerves begin to sprout into the sciatic nerve territory in the dorsal horn. This, together with some recovery of thiamine monophosphate from the remaining sciatic terminals themselves, results in a slow filling in of the gap in the thiamine monophosphate stain. Resection of the cut sciatic nerve, together with adjacent intact nerves, re-establishes the depletion. Substance P and CGRP terminals from nearby intact nerves also sprout into the deafferented sciatic field and this can be demonstrated by the larger than normal area of depletion following section of these nerves when adult. Furthermore, resection of the neonatally cut sciatic nerve when adult also causes some depletion of substance P and CGRP within the sciatic field, indicating a degree of recovery or up-regulation of peptides in surviving cut afferents. However, even after resection of the cut sciatic nerve and nearby intact nerves, substance P and CGRP staining remained in the terminal region. We conclude that while central collateral sprouting does take place in both substance P and CGRP-containing afferents following peripheral nerve section, it cannot account for the lack of depletion of peptides observed.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Neonatal sciatic nerve section results in thiamine monophosphate but not substance P or calcitonin gene-related peptide depletion from the terminal field in the dorsal horn of the rat: the role of collateral sprouting. The expression of substance P, calcitonin gene-related peptide (CGRP) and thiamine monophosphatase in the sciatic nerve terminal field of the lumbar dorsal horn of the rat was examined following neonatal sciatic nerve section and ligation. The total terminal field from L3 to L5 was mapped from semi-serial sections on the treated side and compared to equivalent maps on the contralateral intact side. To obtain a detailed time course of events, data were obtained 4, 7, 10, 15-20 and 40-60 days after sciatic nerve section. At 4-7 days thiamine monophosphate was depleted from the cut nerve terminals resulting in a gap in dorsal horn thiamine monophosphate stain similar to that seen after adult nerve section. In contrast, substance P and CGRP-containing terminals showed only a transient fall in expression in the first week following nerve section and then staining was no different from that seen on the control side. The depletion of peptides normally observed after adult nerve section did not occur. This phenomenon was only observed if the sciatic nerve was cut at birth. Nerve section at 10 days of age resulted in the same pattern of peptide depletion as is observed in the adult. A week after neonatal sciatic nerve section, thiamine monophosphate-containing nerve terminals from nearby intact nerves begin to sprout into the sciatic nerve territory in the dorsal horn. This, together with some recovery of thiamine monophosphate from the remaining sciatic terminals themselves, results in a slow filling in of the gap in the thiamine monophosphate stain. Resection of the cut sciatic nerve, together with adjacent intact nerves, re-establishes the depletion. Substance P and CGRP terminals from nearby intact nerves also sprout into the deafferented sciatic field and this can be demonstrated by the larger than normal area of depletion following section of these nerves when adult. Furthermore, resection of the neonatally cut sciatic nerve when adult also causes some depletion of substance P and CGRP within the sciatic field, indicating a degree of recovery or up-regulation of peptides in surviving cut afferents. However, even after resection of the cut sciatic nerve and nearby intact nerves, substance P and CGRP staining remained in the terminal region. We conclude that while central collateral sprouting does take place in both substance P and CGRP-containing afferents following peripheral nerve section, it cannot account for the lack of depletion of peptides observed.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281526", "title": "Up-regulation of 5-hydroxytryptamine2 and neurokinin-1 receptors associated with serotonin/substance P hyperinnervation in the rat inferior olive.", "content": "The fate of serotonin and substance P receptors following serotonin/substance P hyperinnervation of CNS tissue was investigated in the inferior olivary complex of adult rats subjected to earlier intraventricular administration of 5,6-dihydroxytryptamine. [3H]8-hydroxy-2-(Dl-n-propylamino)tetralin, [3H]5-hydroxytryptamine, [3H]ketanserin and [125I]Bolton-Hunter-substance P were respectively used to label 5-hydroxytryptamine1A, 5-hydroxytryptamine1B, 5-hydroxytryptamine2 and neurokinin-1 receptor sites for quantitative ligand binding autoradiography. Only 5-hydroxytryptamine2 and neurokinin-1 sites were detected in the normal or serotonin/substance P-hyperinnervated inferior olivary complex. In the normal inferior olivary complex, the density of [3H]ketanserin binding (5-hydroxytryptamine2 receptors) was relatively low, being the highest in pars a of the caudal medial accessory olive and the principal olive; moderate in pars c of the caudal medial accessory olive; truly low in the medial and the lateral dorsal accessory olive, nucleus b and pars b of the caudal medial accessory olive; and negligible in the middle medial accessory olive, rostral medial accessory olive and the smaller subnuclei. [125I]Bolton-Hunter-substance P binding (neurokinin-1 receptors) appeared denser, being highest in nucleus beta and the middle medial dorsal accessory olive; moderate in the three portions of the caudal medial accessory olive, the lateral dorsal accessory olive and the dorsal cap of Kooy; low in the rostral medial accessory olive, the ventrolateral outgrowth and the dorsomedial cell column; and very low or null in the principal olive and the medial dorsal accessory olive. After serotonin/substance P hyperinnervation, there were striking increases in the apparent density of both populations of receptor. [3H]Ketanserin binding was now stronger in the most olivary subnuclei, including some in which it had not been found in the normal, such as the middle and the rostral medial accessory olive. [125I]Bolton-Hunter-substance P binding showed even greater elevations in a few subnuclei, such as the principal olive and the dorsomedial cell column; it was now detectable in the medial dorsal accessory olive, unchanged in the dorsal cap of Kooy and the ventrolateral outgrowth, and slightly decreased in the lateral dorsal accessory olive. The normal and altered distributions of both ligands did not match the respective patterns of serotonin and substance P innervation and hyperinnervation previously demonstrated with immunocytochemistry. In some sectors of the inferior olivary complex where both transmitters are presumably co-localized, there was no overlap in the distribution of the respective binding sites either in the normal or in the hyperinnervated state.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Up-regulation of 5-hydroxytryptamine2 and neurokinin-1 receptors associated with serotonin/substance P hyperinnervation in the rat inferior olive. The fate of serotonin and substance P receptors following serotonin/substance P hyperinnervation of CNS tissue was investigated in the inferior olivary complex of adult rats subjected to earlier intraventricular administration of 5,6-dihydroxytryptamine. [3H]8-hydroxy-2-(Dl-n-propylamino)tetralin, [3H]5-hydroxytryptamine, [3H]ketanserin and [125I]Bolton-Hunter-substance P were respectively used to label 5-hydroxytryptamine1A, 5-hydroxytryptamine1B, 5-hydroxytryptamine2 and neurokinin-1 receptor sites for quantitative ligand binding autoradiography. Only 5-hydroxytryptamine2 and neurokinin-1 sites were detected in the normal or serotonin/substance P-hyperinnervated inferior olivary complex. In the normal inferior olivary complex, the density of [3H]ketanserin binding (5-hydroxytryptamine2 receptors) was relatively low, being the highest in pars a of the caudal medial accessory olive and the principal olive; moderate in pars c of the caudal medial accessory olive; truly low in the medial and the lateral dorsal accessory olive, nucleus b and pars b of the caudal medial accessory olive; and negligible in the middle medial accessory olive, rostral medial accessory olive and the smaller subnuclei. [125I]Bolton-Hunter-substance P binding (neurokinin-1 receptors) appeared denser, being highest in nucleus beta and the middle medial dorsal accessory olive; moderate in the three portions of the caudal medial accessory olive, the lateral dorsal accessory olive and the dorsal cap of Kooy; low in the rostral medial accessory olive, the ventrolateral outgrowth and the dorsomedial cell column; and very low or null in the principal olive and the medial dorsal accessory olive. After serotonin/substance P hyperinnervation, there were striking increases in the apparent density of both populations of receptor. [3H]Ketanserin binding was now stronger in the most olivary subnuclei, including some in which it had not been found in the normal, such as the middle and the rostral medial accessory olive. [125I]Bolton-Hunter-substance P binding showed even greater elevations in a few subnuclei, such as the principal olive and the dorsomedial cell column; it was now detectable in the medial dorsal accessory olive, unchanged in the dorsal cap of Kooy and the ventrolateral outgrowth, and slightly decreased in the lateral dorsal accessory olive. The normal and altered distributions of both ligands did not match the respective patterns of serotonin and substance P innervation and hyperinnervation previously demonstrated with immunocytochemistry. In some sectors of the inferior olivary complex where both transmitters are presumably co-localized, there was no overlap in the distribution of the respective binding sites either in the normal or in the hyperinnervated state.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281527", "title": "Kappa-/mu-receptor interactions in the opioid control of the in vivo release of substance P-like material from the rat spinal cord.", "content": "The possible involvement of mu and kappa receptors in the opioid control of the spinal release of substance P-like material was assessed in vivo, in halothane-anaesthetized rats whose intrathecal space was continuously perfused with an artificial cerebrospinal fluid supplemented with various opioid receptor agonists and antagonists. Whereas the intrathecal perfusion with the mu agonist DAGO (10 microM) significantly enhanced (approximately + 50%) the spontaneous release of substance P-like material, that with the kappa agonist U 50488 H (10 microM) produced no change in the peptide outflow. The respective antagonists naloxone (10 microM) for the mu receptors and nor-binaltorphimine (10 microM) for the kappa receptors did not affect the spontaneous release of substance P-like material, indicating that endogenous opioids acting at mu and kappa receptors do not exert a tonic control on substance P-containing neurons in the spinal cord of halothane-anaesthetized rats. However, as expected from the involvement of mu receptors, the stimulatory effect of DAGO on the peptide outflow could be prevented by naloxone but not norbinaltorphimine. Furthermore, instead of an increase with DAGO alone, a significant decrease in the spinal release of substance P-like material was observed upon the intrathecal perfusion with DAGO plus U 50488 H. Additional experiments with the respective mu and kappa antagonists naloxone and nor-binaltorphimine demonstrated that this effect actually resulted from the simultaneous stimulation of mu and kappa receptors.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Kappa-/mu-receptor interactions in the opioid control of the in vivo release of substance P-like material from the rat spinal cord. The possible involvement of mu and kappa receptors in the opioid control of the spinal release of substance P-like material was assessed in vivo, in halothane-anaesthetized rats whose intrathecal space was continuously perfused with an artificial cerebrospinal fluid supplemented with various opioid receptor agonists and antagonists. Whereas the intrathecal perfusion with the mu agonist DAGO (10 microM) significantly enhanced (approximately + 50%) the spontaneous release of substance P-like material, that with the kappa agonist U 50488 H (10 microM) produced no change in the peptide outflow. The respective antagonists naloxone (10 microM) for the mu receptors and nor-binaltorphimine (10 microM) for the kappa receptors did not affect the spontaneous release of substance P-like material, indicating that endogenous opioids acting at mu and kappa receptors do not exert a tonic control on substance P-containing neurons in the spinal cord of halothane-anaesthetized rats. However, as expected from the involvement of mu receptors, the stimulatory effect of DAGO on the peptide outflow could be prevented by naloxone but not norbinaltorphimine. Furthermore, instead of an increase with DAGO alone, a significant decrease in the spinal release of substance P-like material was observed upon the intrathecal perfusion with DAGO plus U 50488 H. Additional experiments with the respective mu and kappa antagonists naloxone and nor-binaltorphimine demonstrated that this effect actually resulted from the simultaneous stimulation of mu and kappa receptors.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281528", "title": "Morphology and distribution of neuropeptide-containing neurons in human cerebral cortex.", "content": "Biopsies of human cerebral cortex were fixed by immersion and immunostained for the detection of neuropeptides in neuronal cell bodies and axons. Four neuropeptides (neuropeptide Y, somatostatin, , substance P and cholecystokinin) were visualized in a series of adjacent sections. All populations of immunoreactive neurons had a morphology characteristic of interneurons, with variations in dendritic arborizations and laminar distribution. The cholecystokinin-immunoreactive neurons were most numerous in the supragranular layers, whereas neurons containing the other three peptides occurred mainly in infragranular layers, or even in neurons populating the subcortical white matter. Quantitatively, each population of neuropeptide-containing neurons accounted for 1.4-2.5% of the total neuronal population. The distribution of these neurons varied slightly between cytoarchitectonic divisions, with substance P- and somatostatin-immunoreactive neurons dominating in the temporal lobe and cholecystokinin-immunoreactive neurons in the frontal lobe. Neuropeptide Y-immunoreactive neurons dominated in the gray matter of the frontal half of the hemisphere and in the subcortical white matter of the caudal half of the hemisphere. Furthermore, co-existence of neuropeptide Y or substance P immunoreactivity within somatostatin-immunoreactive neurons could be demonstrated using double labeling immunofluorescence techniques. The axonal plexuses immunoreactive for neuropeptide Y, somatostatin, or substance P were distributed in all layers, with a strong predominance of horizontally oriented fibers in layer I, a moderate plexus of randomly oriented fibers in the supra- and infragranular layers, and a slightly weaker innervation of layer IV. Immunoreactive axons formed, in addition, complex terminal arbors, mostly in older subjects, suggesting that they resulted from an as yet undefined aging process. The present study underlines several aspects of the organization of the neuropeptide-containing neurons of the human cerebral cortex, which are of particular interest in the light of the involvement of these neurons in several neurodegenerative diseases.", "contents": "Morphology and distribution of neuropeptide-containing neurons in human cerebral cortex. Biopsies of human cerebral cortex were fixed by immersion and immunostained for the detection of neuropeptides in neuronal cell bodies and axons. Four neuropeptides (neuropeptide Y, somatostatin, , substance P and cholecystokinin) were visualized in a series of adjacent sections. All populations of immunoreactive neurons had a morphology characteristic of interneurons, with variations in dendritic arborizations and laminar distribution. The cholecystokinin-immunoreactive neurons were most numerous in the supragranular layers, whereas neurons containing the other three peptides occurred mainly in infragranular layers, or even in neurons populating the subcortical white matter. Quantitatively, each population of neuropeptide-containing neurons accounted for 1.4-2.5% of the total neuronal population. The distribution of these neurons varied slightly between cytoarchitectonic divisions, with substance P- and somatostatin-immunoreactive neurons dominating in the temporal lobe and cholecystokinin-immunoreactive neurons in the frontal lobe. Neuropeptide Y-immunoreactive neurons dominated in the gray matter of the frontal half of the hemisphere and in the subcortical white matter of the caudal half of the hemisphere. Furthermore, co-existence of neuropeptide Y or substance P immunoreactivity within somatostatin-immunoreactive neurons could be demonstrated using double labeling immunofluorescence techniques. The axonal plexuses immunoreactive for neuropeptide Y, somatostatin, or substance P were distributed in all layers, with a strong predominance of horizontally oriented fibers in layer I, a moderate plexus of randomly oriented fibers in the supra- and infragranular layers, and a slightly weaker innervation of layer IV. Immunoreactive axons formed, in addition, complex terminal arbors, mostly in older subjects, suggesting that they resulted from an as yet undefined aging process. The present study underlines several aspects of the organization of the neuropeptide-containing neurons of the human cerebral cortex, which are of particular interest in the light of the involvement of these neurons in several neurodegenerative diseases."} {"id": "PMID:1281529", "title": "GABAergic and catecholaminergic innervation of mediobasal hypothalamic beta-endorphin cells projecting to the medial preoptic area.", "content": "In the absence of cellular estrogen receptors or proven direct estrogen action in the rat, it is assumed that estrogen indirectly regulates the secretory activity of the preoptic area luteinizing hormone-releasing hormone-producing cells. We have previously shown that pro-opiomelanocortin neurons in the arcuate nucleus of the rat send axons rostrally to connect with luteinizing hormone-releasing hormone neurons of the preoptic area. An experiment combining retrograde tracing and double-immunostaining was used to test the hypothesis that rat GABAergic and/or catecholaminergic neurons can influence luteinizing hormone-releasing hormone-producing cells via mediobasal hypothalamic beta-endorphin neurons. The retrograde tracer horseradish peroxidase was injected into the medial preoptic area; two days later, arcuate nucleus Vibratome sections were double-immunostained for beta-endorphin and glutamate decarboxylase or tyrosine hydroxylase. Light and electron microscopic analysis of these triple-labeled sections demonstrated that a population of beta-endorphin-immunoreactive neurons concentrated in the ventromedial arcuate nucleus contain retrogradely transported horseradish peroxidase granules and form synaptic contacts with glutamate decarboxylase- and tyrosine hydroxylase-immunoreactive axon terminals. The present data suggest that arcuate nucleus GABA and catecholamine fibers may influence luteinizing hormone-releasing hormone-containing neurons via projective pro-opiomelanocortin cells.", "contents": "GABAergic and catecholaminergic innervation of mediobasal hypothalamic beta-endorphin cells projecting to the medial preoptic area. In the absence of cellular estrogen receptors or proven direct estrogen action in the rat, it is assumed that estrogen indirectly regulates the secretory activity of the preoptic area luteinizing hormone-releasing hormone-producing cells. We have previously shown that pro-opiomelanocortin neurons in the arcuate nucleus of the rat send axons rostrally to connect with luteinizing hormone-releasing hormone neurons of the preoptic area. An experiment combining retrograde tracing and double-immunostaining was used to test the hypothesis that rat GABAergic and/or catecholaminergic neurons can influence luteinizing hormone-releasing hormone-producing cells via mediobasal hypothalamic beta-endorphin neurons. The retrograde tracer horseradish peroxidase was injected into the medial preoptic area; two days later, arcuate nucleus Vibratome sections were double-immunostained for beta-endorphin and glutamate decarboxylase or tyrosine hydroxylase. Light and electron microscopic analysis of these triple-labeled sections demonstrated that a population of beta-endorphin-immunoreactive neurons concentrated in the ventromedial arcuate nucleus contain retrogradely transported horseradish peroxidase granules and form synaptic contacts with glutamate decarboxylase- and tyrosine hydroxylase-immunoreactive axon terminals. The present data suggest that arcuate nucleus GABA and catecholamine fibers may influence luteinizing hormone-releasing hormone-containing neurons via projective pro-opiomelanocortin cells."} {"id": "PMID:1281530", "title": "Protein kinase C activation by phorbol esters induces chromaffin cell cortical filamentous actin disassembly and increases the initial rate of exocytosis in response to nicotinic receptor stimulation.", "content": "Nicotinic stimulation and high K+ depolarization of bovine chromaffin cells cause disassembly of cortical filamentous actin networks. Previous work from our laboratory has demonstrated that disassembly of actin filaments is Ca(2+)-dependent, precedes exocytosis and occurs in cortical areas of low cytoplasmic viscosity which are the sites of exocytosis. It has also been suggested that protein kinase C is involved in catecholamine secretion from chromaffin cells. Therefore, the possibility that protein kinase C activation might be implicated in cortical filamentous actin disassembly was investigated. Here we report that phorbol myristate acetate, a protein kinase C activator, causes cortical filamentous actin disassembly. Short-term phorbol ester treatment does not alter the morphology of chromaffin cells; however, 1 h after phorbol ester exposure an increase in cell flattening and membrane ruffling is observed. Phorbol ester-induced cortical filamentous actin disassembly is inhibited by protein kinase C activity inhibitors, is independent of extracellular Ca2+ and has a slower time course than that induced by either nicotinic receptor stimulation or K(+)-depolarization. Phorbol ester effects are likely to be mediated by activation of protein kinase C and not by any changes in intracellular Ca2+ levels, as indicated by measurements of Ca2+ transients. Pretreatment of chromaffin cells with phorbol myristate acetate increases the initial rate of nicotine-evoked catecholamine release. Nicotine-induced cortical actin filament disassembly and catecholamine secretion are partially (29-40%) inhibited by pretreatment of cells with either calphostin C, staurosporine or sphingosine. The results suggest that protein kinase C may be involved in the reorganization of the cortical actin filament network priming the cells for release by removing a barrier to secretory granule mobility. However, its role in exocytosis is modulatory but not essential.", "contents": "Protein kinase C activation by phorbol esters induces chromaffin cell cortical filamentous actin disassembly and increases the initial rate of exocytosis in response to nicotinic receptor stimulation. Nicotinic stimulation and high K+ depolarization of bovine chromaffin cells cause disassembly of cortical filamentous actin networks. Previous work from our laboratory has demonstrated that disassembly of actin filaments is Ca(2+)-dependent, precedes exocytosis and occurs in cortical areas of low cytoplasmic viscosity which are the sites of exocytosis. It has also been suggested that protein kinase C is involved in catecholamine secretion from chromaffin cells. Therefore, the possibility that protein kinase C activation might be implicated in cortical filamentous actin disassembly was investigated. Here we report that phorbol myristate acetate, a protein kinase C activator, causes cortical filamentous actin disassembly. Short-term phorbol ester treatment does not alter the morphology of chromaffin cells; however, 1 h after phorbol ester exposure an increase in cell flattening and membrane ruffling is observed. Phorbol ester-induced cortical filamentous actin disassembly is inhibited by protein kinase C activity inhibitors, is independent of extracellular Ca2+ and has a slower time course than that induced by either nicotinic receptor stimulation or K(+)-depolarization. Phorbol ester effects are likely to be mediated by activation of protein kinase C and not by any changes in intracellular Ca2+ levels, as indicated by measurements of Ca2+ transients. Pretreatment of chromaffin cells with phorbol myristate acetate increases the initial rate of nicotine-evoked catecholamine release. Nicotine-induced cortical actin filament disassembly and catecholamine secretion are partially (29-40%) inhibited by pretreatment of cells with either calphostin C, staurosporine or sphingosine. The results suggest that protein kinase C may be involved in the reorganization of the cortical actin filament network priming the cells for release by removing a barrier to secretory granule mobility. However, its role in exocytosis is modulatory but not essential."} {"id": "PMID:1281531", "title": "An inhibitor of nitric oxide synthesis prevents memory formation in the chick.", "content": "Memory formation is presumed to require retrograde communication across synaptic junctions. Nitric oxide (NO) is a putative retrograde messenger at N-methyl-D-aspartate (NMDA)-mediated synapses [8, 9]. Inhibitors of nitric oxide synthesis block initiation of long-term potentiation [2, 3, 19]. Memory for a one-trial passive avoidance task in the young chick involves an NMDA-linked intracellular cascade culminating in lasting modulation of synaptic morphology and [6, 18]. Here we show that injection of the nitric oxide synthase inhibitor N-nitro-L-arginine prior to training results in amnesia for the passive avoidance task; the amnesia can be overcome by injecting L-arginine along with the inhibitor. Thus we have verified for the first time experimentally that NO plays a role in memory formation.", "contents": "An inhibitor of nitric oxide synthesis prevents memory formation in the chick. Memory formation is presumed to require retrograde communication across synaptic junctions. Nitric oxide (NO) is a putative retrograde messenger at N-methyl-D-aspartate (NMDA)-mediated synapses [8, 9]. Inhibitors of nitric oxide synthesis block initiation of long-term potentiation [2, 3, 19]. Memory for a one-trial passive avoidance task in the young chick involves an NMDA-linked intracellular cascade culminating in lasting modulation of synaptic morphology and [6, 18]. Here we show that injection of the nitric oxide synthase inhibitor N-nitro-L-arginine prior to training results in amnesia for the passive avoidance task; the amnesia can be overcome by injecting L-arginine along with the inhibitor. Thus we have verified for the first time experimentally that NO plays a role in memory formation."} {"id": "PMID:1281532", "title": "Striatal neuropeptide levels in Parkinson's disease patients.", "content": "Substance P (SP), Met-enkephalin (Met-enk) and cholecystokinin-8-S (CCK-8-S) were measured by a combined HPLC/RIA method in the caudate nucleus and anterior putamen from controls and from Parkinson's disease (PD) patients. SP levels were reduced in caudate in PD, but unchanged in putamen. No differences in Met-enk content were found in parkinsonians compared to controls. However, a significant correlation between DA and Met-enk levels in caudate nucleus from PD was observed. The concentration of CCK-8-S was unaltered in caudate nucleus or putamen in PD. The decrease in caudate nucleus SP levels might be related to the decrease in nigral SP levels in PD, while the reduction in Met-enk levels appears to be a feature of a subgroup of parkinsonian patients.", "contents": "Striatal neuropeptide levels in Parkinson's disease patients. Substance P (SP), Met-enkephalin (Met-enk) and cholecystokinin-8-S (CCK-8-S) were measured by a combined HPLC/RIA method in the caudate nucleus and anterior putamen from controls and from Parkinson's disease (PD) patients. SP levels were reduced in caudate in PD, but unchanged in putamen. No differences in Met-enk content were found in parkinsonians compared to controls. However, a significant correlation between DA and Met-enk levels in caudate nucleus from PD was observed. The concentration of CCK-8-S was unaltered in caudate nucleus or putamen in PD. The decrease in caudate nucleus SP levels might be related to the decrease in nigral SP levels in PD, while the reduction in Met-enk levels appears to be a feature of a subgroup of parkinsonian patients."} {"id": "PMID:1281533", "title": "A subpopulation of hippocampal glial cells specific for the zinc-containing mossy fibre zone in man.", "content": "The projection of the zinc-containing axons of granule cells of the fascia dentata, e.g. the mossy fibres, is restricted to the hilar region and sector CA3 of the hippocampus. Serial sections of human hippocampi were stained for zinc-containing fibres with a non-perfusion Timm method, while adjacent ones were stained with Darrow red and aldehydefuchsin. GFAP, glutamine synthetase immunocytochemistry and a specific silver stain were employed to label other subtypes of astrocytes. The distribution of Timm-stained areas correlates only with the distribution of aldehydefuchsin-positive glial cells, most probably astrocytes. Since glial cells regulate axonal outgrowth in a region-specific manner, it is temptative to speculate that the aldehydefuchsin-positive glial cell is a candidate for a specific neuron-glia interaction which is somehow involved in the control of outgrowth of mossy fibres.", "contents": "A subpopulation of hippocampal glial cells specific for the zinc-containing mossy fibre zone in man. The projection of the zinc-containing axons of granule cells of the fascia dentata, e.g. the mossy fibres, is restricted to the hilar region and sector CA3 of the hippocampus. Serial sections of human hippocampi were stained for zinc-containing fibres with a non-perfusion Timm method, while adjacent ones were stained with Darrow red and aldehydefuchsin. GFAP, glutamine synthetase immunocytochemistry and a specific silver stain were employed to label other subtypes of astrocytes. The distribution of Timm-stained areas correlates only with the distribution of aldehydefuchsin-positive glial cells, most probably astrocytes. Since glial cells regulate axonal outgrowth in a region-specific manner, it is temptative to speculate that the aldehydefuchsin-positive glial cell is a candidate for a specific neuron-glia interaction which is somehow involved in the control of outgrowth of mossy fibres."} {"id": "PMID:1281534", "title": "Evidence for upregulation of galanin synthesis in rat glial cells in vivo after colchicine treatment.", "content": "The localization of galanin (GAL) and GAL mRNA was studied in rat brain after colchicine or vinblastine treatment using in situ hybridization and immunohistochemistry. GAL-like immunoreactivity was found in glial cells, presumably activated microglia, in the cortex, caudate nucleus and septum, mainly on the injection side. GAL mRNA expression was found in small cells in the same areas with an overlapping distribution, including the adjacent white matter. The results suggest that the glial cells initiate synthesis of the peptide GAL in response to intraventricular injection of high doses of the 2 mitosis inhibitors.", "contents": "Evidence for upregulation of galanin synthesis in rat glial cells in vivo after colchicine treatment. The localization of galanin (GAL) and GAL mRNA was studied in rat brain after colchicine or vinblastine treatment using in situ hybridization and immunohistochemistry. GAL-like immunoreactivity was found in glial cells, presumably activated microglia, in the cortex, caudate nucleus and septum, mainly on the injection side. GAL mRNA expression was found in small cells in the same areas with an overlapping distribution, including the adjacent white matter. The results suggest that the glial cells initiate synthesis of the peptide GAL in response to intraventricular injection of high doses of the 2 mitosis inhibitors."} {"id": "PMID:1281535", "title": "Rationale of combining radiation and interferon for the treatment of cervical cancer.", "content": "The recent surge of interest in the mechanisms of action of biomodulators, also known as biological response modifiers, offers a new avenue of approach in the treatment of cancer. The in vitro antitumor activities of these agents, such as interferons, when combined with chemo- or radiotherapy, have generated enthusiasm among clinicians for developing clinical trials. In recent years many antineoplastic agents have been investigated as neoadjuvant or adjuvant therapy for patients with cervical cancer in an attempt to improve local control and to decrease incidence of metastasis. Normal tissue tolerance limits the potential combinations of standard cytotoxic chemotherapeutic agents with radiation. Interferon used as a radiomodulator has been studied mainly for the treatment of lung cancer with promising results. In this paper we report the rationale of combining interferon and radiation for the treatment of patients with cervical cancer.", "contents": "Rationale of combining radiation and interferon for the treatment of cervical cancer. The recent surge of interest in the mechanisms of action of biomodulators, also known as biological response modifiers, offers a new avenue of approach in the treatment of cancer. The in vitro antitumor activities of these agents, such as interferons, when combined with chemo- or radiotherapy, have generated enthusiasm among clinicians for developing clinical trials. In recent years many antineoplastic agents have been investigated as neoadjuvant or adjuvant therapy for patients with cervical cancer in an attempt to improve local control and to decrease incidence of metastasis. Normal tissue tolerance limits the potential combinations of standard cytotoxic chemotherapeutic agents with radiation. Interferon used as a radiomodulator has been studied mainly for the treatment of lung cancer with promising results. In this paper we report the rationale of combining interferon and radiation for the treatment of patients with cervical cancer."} {"id": "PMID:1281536", "title": "Morphologic and immunohistochemical observations on the mammary and extramammary Paget's disease: implications for the histogenesis.", "content": "Using a panel of three anti-CK MoAbs, belonging to Gown's Classes II, III and IV, the Paget's cells shown a variable reactivity to such antibodies indicating a more frequent immunocytochemical similarity to the cells of the epidermal basal-ductal system than to the cells of the glandular secreting section of the epidermal derivatives. According these findings the P.C. not necessarily is the result of a cellular migration from ductal section toward the epidermis, but may arise from a epidermal basal-stem cell, from a ductal or more rarely from glandular secreting cell. This assumption is enforced also by the expression of the CEA from morphologically bonafide basal epidermal cells in proximity of the pagetic lesion.", "contents": "Morphologic and immunohistochemical observations on the mammary and extramammary Paget's disease: implications for the histogenesis. Using a panel of three anti-CK MoAbs, belonging to Gown's Classes II, III and IV, the Paget's cells shown a variable reactivity to such antibodies indicating a more frequent immunocytochemical similarity to the cells of the epidermal basal-ductal system than to the cells of the glandular secreting section of the epidermal derivatives. According these findings the P.C. not necessarily is the result of a cellular migration from ductal section toward the epidermis, but may arise from a epidermal basal-stem cell, from a ductal or more rarely from glandular secreting cell. This assumption is enforced also by the expression of the CEA from morphologically bonafide basal epidermal cells in proximity of the pagetic lesion."} {"id": "PMID:1281539", "title": "Effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on hemopoiesis and survival rate following allogeneic bone marrow transplantation in mice.", "content": "The effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the survival rate and hemopoiesis after allogeneic bone marrow transplantation (BMT) were examined. Specific pathogen-free (SPF) C3H mice and germ-free C3H mice, kept in an isolator for germ-free animals, received 10 Gy of total body irradiation (TBI) and all the mice died by day 9 after TBI. These survival rates were improved by BMT. In the case of SPF mice, survival rates at 14 and 100 days were 33% (12/36), 17% (6/36) and in the case of germ-free mice they were 79% (15/19), 74% (14/19) respectively. When SPF mice received rhG-CSF (30 micrograms/kg/day) subcutaneously for 14 consecutive days following BMT, their survival rates were improved to 79% (30/38), 79% (30/38) respectively. The survival rate of rhG-CSF treated SPF mice were equal to that of germ-free mice. When the effect of rhG-CSF treatment on hemopoiesis of SPF mice after allogeneic BMT was examined various hematopoietic progenitor cells in the bone marrow and spleen increased until day 10 after, BMT, while only neutrophils increased in the peripheral blood during the period. No adverse effects of rhG-CSF were observed throughout the study period. It was suggested that in SPF mice treated with rhG-CSF after BMT, the neutrophil recovered in counts quickly and increased neutrophil prevented endogenous infections and improved the survival rate without apparent complications.", "contents": "Effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on hemopoiesis and survival rate following allogeneic bone marrow transplantation in mice. The effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) on the survival rate and hemopoiesis after allogeneic bone marrow transplantation (BMT) were examined. Specific pathogen-free (SPF) C3H mice and germ-free C3H mice, kept in an isolator for germ-free animals, received 10 Gy of total body irradiation (TBI) and all the mice died by day 9 after TBI. These survival rates were improved by BMT. In the case of SPF mice, survival rates at 14 and 100 days were 33% (12/36), 17% (6/36) and in the case of germ-free mice they were 79% (15/19), 74% (14/19) respectively. When SPF mice received rhG-CSF (30 micrograms/kg/day) subcutaneously for 14 consecutive days following BMT, their survival rates were improved to 79% (30/38), 79% (30/38) respectively. The survival rate of rhG-CSF treated SPF mice were equal to that of germ-free mice. When the effect of rhG-CSF treatment on hemopoiesis of SPF mice after allogeneic BMT was examined various hematopoietic progenitor cells in the bone marrow and spleen increased until day 10 after, BMT, while only neutrophils increased in the peripheral blood during the period. No adverse effects of rhG-CSF were observed throughout the study period. It was suggested that in SPF mice treated with rhG-CSF after BMT, the neutrophil recovered in counts quickly and increased neutrophil prevented endogenous infections and improved the survival rate without apparent complications."} {"id": "PMID:1281537", "title": "Human papillomavirus in oral verrucal-papillary lesions. A comparative histological, clinical and immunohistochemical study.", "content": "The purpose of this study was to determine the presence of Human Papillomavirus (HPV) virions in the verrucal-papillary (OVP) lesions by clinical, histological and immunohistochemical [peroxidase-antiperoxidase (PAP) features]. Thirty seven positive cases were compared with 47 negative cases. Considerable overlapping of clinical and histological features can be seen among all these lesions. The study provides evidence that there are no clinical or histologic features with taken alone are strongly correlated with the presence of virions in oral lesions.", "contents": "Human papillomavirus in oral verrucal-papillary lesions. A comparative histological, clinical and immunohistochemical study. The purpose of this study was to determine the presence of Human Papillomavirus (HPV) virions in the verrucal-papillary (OVP) lesions by clinical, histological and immunohistochemical [peroxidase-antiperoxidase (PAP) features]. Thirty seven positive cases were compared with 47 negative cases. Considerable overlapping of clinical and histological features can be seen among all these lesions. The study provides evidence that there are no clinical or histologic features with taken alone are strongly correlated with the presence of virions in oral lesions."} {"id": "PMID:1281538", "title": "Primary papillary serous tumor of the peritoneum. Report of a case.", "content": "In the present report we describe a rare papillary serous tumor of the peritoneum occurring in a woman without evidence of ovarian neoplasia. Histochemical, immunohistochemical and ultrastructural findings are reported, with particular emphasis on electron microscopic results and on their importance in the differential diagnosis with malignant mesotheliomas.", "contents": "Primary papillary serous tumor of the peritoneum. Report of a case. In the present report we describe a rare papillary serous tumor of the peritoneum occurring in a woman without evidence of ovarian neoplasia. Histochemical, immunohistochemical and ultrastructural findings are reported, with particular emphasis on electron microscopic results and on their importance in the differential diagnosis with malignant mesotheliomas."} {"id": "PMID:1281541", "title": "Suppression of the onset of myelination extends the permissive period for the functional repair of embryonic spinal cord.", "content": "In an embryonic chicken, transection of the thoracic spinal cord prior to embryonic day (E) 13 (of the 21-day developmental period) results in complete neuroanatomical repair and functional locomotor recovery. Conversely, repair rapidly diminishes following a transection on E13-E14 and is nonexistent after an E15 transection. The myelination of fiber tracts within the spinal cord also begins on E13, coincident with the transition from permissive to restrictive repair periods. The onset of myelination can be delayed (dysmyelination) until later in development by the direct injection into the thoracic cord on E9-E12 of a monoclonal antibody to galactocerebroside, plus homologous complement. In such a dysmyelinated embryo, a subsequent transection of the thoracic cord as late as E15 resulted in complete neuroanatomical repair and functional recovery (i.e., extended the permissive period for repair).", "contents": "Suppression of the onset of myelination extends the permissive period for the functional repair of embryonic spinal cord. In an embryonic chicken, transection of the thoracic spinal cord prior to embryonic day (E) 13 (of the 21-day developmental period) results in complete neuroanatomical repair and functional locomotor recovery. Conversely, repair rapidly diminishes following a transection on E13-E14 and is nonexistent after an E15 transection. The myelination of fiber tracts within the spinal cord also begins on E13, coincident with the transition from permissive to restrictive repair periods. The onset of myelination can be delayed (dysmyelination) until later in development by the direct injection into the thoracic cord on E9-E12 of a monoclonal antibody to galactocerebroside, plus homologous complement. In such a dysmyelinated embryo, a subsequent transection of the thoracic cord as late as E15 resulted in complete neuroanatomical repair and functional recovery (i.e., extended the permissive period for repair)."} {"id": "PMID:1281542", "title": "Secondary structure of Src homology 2 domain of c-Abl by heteronuclear NMR spectroscopy in solution.", "content": "The Src homology 2 (SH2) domain is a recognition motif thought to mediate the association of the cytoplasmic proteins involved in signal transduction by binding to phosphotyrosyl-containing sequences in proteins. Assignments of nearly all 1H and 15N resonances of the SH2 domain from the c-Abl protein-tyrosine kinase have been obtained from homonuclear and heteronuclear NMR experiments. The secondary structure has been elucidated from the pattern of nuclear Overhauser effects, from vicinal coupling constants, and from observation of slowly exchanging amino hydrogens. The secondary structure contains two alpha-helices and eight beta-strands, six of which are arranged in two contiguous, antiparallel beta-sheets. Residues believed to be involved in phosphotyrosyl ligand binding are on a face of one beta-sheet. The alignment of homologous sequences on the basis of secondary structure suggests a conserved global fold in a family of SH2 domains.", "contents": "Secondary structure of Src homology 2 domain of c-Abl by heteronuclear NMR spectroscopy in solution. The Src homology 2 (SH2) domain is a recognition motif thought to mediate the association of the cytoplasmic proteins involved in signal transduction by binding to phosphotyrosyl-containing sequences in proteins. Assignments of nearly all 1H and 15N resonances of the SH2 domain from the c-Abl protein-tyrosine kinase have been obtained from homonuclear and heteronuclear NMR experiments. The secondary structure has been elucidated from the pattern of nuclear Overhauser effects, from vicinal coupling constants, and from observation of slowly exchanging amino hydrogens. The secondary structure contains two alpha-helices and eight beta-strands, six of which are arranged in two contiguous, antiparallel beta-sheets. Residues believed to be involved in phosphotyrosyl ligand binding are on a face of one beta-sheet. The alignment of homologous sequences on the basis of secondary structure suggests a conserved global fold in a family of SH2 domains."} {"id": "PMID:1281543", "title": "Regulation of mouse gamete interaction by a sperm tyrosine kinase.", "content": "A 95-kDa mouse sperm protein has been previously identified as a putative receptor involved in the sperm-egg interactions that lead to fertilization. The ligand for this receptor is the zona pellucida glycoprotein ZP3. This constituent of the oocyte-specific extracellular matrix mediates not only sperm binding to the zona but also triggers acrosomal exocytosis. The latter, also termed the acrosome reaction, is a key regulatory event upon which fertilization is absolutely dependent. Previously, we showed that the 95-kDa protein that binds ZP3 is a substrate for tyrosine kinase, and its phosphotyrosine content increases after sperm-zona pellucida binding. Here, we show the presence of protein tyrosine kinase activity in sperm plasma membranes and in electroeluted 95-kDa protein. The tyrosine kinase activity of the isolated protein is stimulated by solubilized zona pellucida and inhibited by tyrphostin RG-50864, a membrane-permeable tyrosine kinase inhibitor. Furthermore, tyrphostin inhibits zona-triggered acrosomal exocytosis in a dose-dependent manner. These findings indicate that the 95-kDa protein participates in a critical regulatory event of gamete interaction; moreover, our experiments suggest that sperm protein tyrosine kinase may be an excellent target for the control of fertility.", "contents": "Regulation of mouse gamete interaction by a sperm tyrosine kinase. A 95-kDa mouse sperm protein has been previously identified as a putative receptor involved in the sperm-egg interactions that lead to fertilization. The ligand for this receptor is the zona pellucida glycoprotein ZP3. This constituent of the oocyte-specific extracellular matrix mediates not only sperm binding to the zona but also triggers acrosomal exocytosis. The latter, also termed the acrosome reaction, is a key regulatory event upon which fertilization is absolutely dependent. Previously, we showed that the 95-kDa protein that binds ZP3 is a substrate for tyrosine kinase, and its phosphotyrosine content increases after sperm-zona pellucida binding. Here, we show the presence of protein tyrosine kinase activity in sperm plasma membranes and in electroeluted 95-kDa protein. The tyrosine kinase activity of the isolated protein is stimulated by solubilized zona pellucida and inhibited by tyrphostin RG-50864, a membrane-permeable tyrosine kinase inhibitor. Furthermore, tyrphostin inhibits zona-triggered acrosomal exocytosis in a dose-dependent manner. These findings indicate that the 95-kDa protein participates in a critical regulatory event of gamete interaction; moreover, our experiments suggest that sperm protein tyrosine kinase may be an excellent target for the control of fertility."} {"id": "PMID:1281544", "title": "Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding.", "content": "The translation of ferritin mRNA and degradation of transferrin receptor mRNA are regulated by the interaction of an RNA-binding protein, the iron-responsive element binding protein (IRE-BP), with RNA stem-loop structures known as iron-responsive elements (IREs) contained within these transcripts. IRE-BP produced in iron-replete cells has aconitase (EC 4.2.1.3) activity. The protein shows extensive sequence homology with mitochondrial aconitase, and sequences of peptides prepared from cytosolic aconitase are identical with peptides of IRE-BP. As an active aconitase, IRE-BP is expected to have an Fe-S cluster, in analogy to other aconitases. This Fe-S cluster has been implicated as the region of the protein that senses intracellular iron levels and accordingly modifies the ability of the IRE-BP to interact with IREs. Expression of the IRE-BP in cultured cells has revealed that the IRE-BP functions either as an active aconitase, when the cells are iron-replete, or as an active RNA-binding protein, when the cells are iron-depleted. We compare properties of purified authentic cytosolic aconitase from beef liver with those of IRE-BP from tissue culture cells and establish that characteristics of the physiologically relevant form of the protein from iron-depleted cells resemble those of cytosolic aconitase apoprotein. We demonstrate that loss of the labile fourth iron atom of the Fe-S cluster results in loss of aconitase activity, but that more extensive cluster alteration is required before the IRE-BP acquires the capacity to bind RNA with the affinity seen in vivo. These results are consistent with a model in which the cubane Fe-S cluster is disassembled when intracellular iron is depleted.", "contents": "Cellular regulation of the iron-responsive element binding protein: disassembly of the cubane iron-sulfur cluster results in high-affinity RNA binding. The translation of ferritin mRNA and degradation of transferrin receptor mRNA are regulated by the interaction of an RNA-binding protein, the iron-responsive element binding protein (IRE-BP), with RNA stem-loop structures known as iron-responsive elements (IREs) contained within these transcripts. IRE-BP produced in iron-replete cells has aconitase (EC 4.2.1.3) activity. The protein shows extensive sequence homology with mitochondrial aconitase, and sequences of peptides prepared from cytosolic aconitase are identical with peptides of IRE-BP. As an active aconitase, IRE-BP is expected to have an Fe-S cluster, in analogy to other aconitases. This Fe-S cluster has been implicated as the region of the protein that senses intracellular iron levels and accordingly modifies the ability of the IRE-BP to interact with IREs. Expression of the IRE-BP in cultured cells has revealed that the IRE-BP functions either as an active aconitase, when the cells are iron-replete, or as an active RNA-binding protein, when the cells are iron-depleted. We compare properties of purified authentic cytosolic aconitase from beef liver with those of IRE-BP from tissue culture cells and establish that characteristics of the physiologically relevant form of the protein from iron-depleted cells resemble those of cytosolic aconitase apoprotein. We demonstrate that loss of the labile fourth iron atom of the Fe-S cluster results in loss of aconitase activity, but that more extensive cluster alteration is required before the IRE-BP acquires the capacity to bind RNA with the affinity seen in vivo. These results are consistent with a model in which the cubane Fe-S cluster is disassembled when intracellular iron is depleted."} {"id": "PMID:1281545", "title": "In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides.", "content": "The c-myb protooncogene encodes proteins that are critical for hematopoietic cell proliferation and development. Disrupting c-myb function might, therefore, prove an effective therapeutic strategy for controlling leukemic cell growth. Antisense oligodeoxynucleotides have been utilized for this purpose in vitro, but their in vivo efficacy has not been reported. We therefore established human leukemia-scid mouse chimeras with K562 cells and treated diseased animals with phosphorothioate-modified antisense oligodeoxynucleotides. K562 cells express the c-myb protooncogene, which served as the target for the antisense DNA. They also express the tumor-specific bcr-abl oncogene that was utilized to track the human cells in the mouse host. Once circulating leukemic blast cells had been detected, the survival of untreated control mice was 6 +/- 3 days (mean +/- SD). The survival of animals treated for 7 or 14 days with either sense or scrambled-sequence c-myb oligodeoxynucleotides was not statistically different from the control animals. In distinct contrast, animals treated for similar lengths of time with antisense c-myb oligodeoxynucleotides survived at least 3.5 times longer than the various control animals. In addition, animals receiving antisense c-myb DNA had significantly less disease at the two sites most frequently manifesting leukemic cell infiltration, the central nervous system and the ovary. These results suggest that phosphorothioate-modified antisense DNA may be efficacious for the treatment of human leukemia in vivo, and by analogy, for the treatment of other human neoplasias.", "contents": "In vivo treatment of human leukemia in a scid mouse model with c-myb antisense oligodeoxynucleotides. The c-myb protooncogene encodes proteins that are critical for hematopoietic cell proliferation and development. Disrupting c-myb function might, therefore, prove an effective therapeutic strategy for controlling leukemic cell growth. Antisense oligodeoxynucleotides have been utilized for this purpose in vitro, but their in vivo efficacy has not been reported. We therefore established human leukemia-scid mouse chimeras with K562 cells and treated diseased animals with phosphorothioate-modified antisense oligodeoxynucleotides. K562 cells express the c-myb protooncogene, which served as the target for the antisense DNA. They also express the tumor-specific bcr-abl oncogene that was utilized to track the human cells in the mouse host. Once circulating leukemic blast cells had been detected, the survival of untreated control mice was 6 +/- 3 days (mean +/- SD). The survival of animals treated for 7 or 14 days with either sense or scrambled-sequence c-myb oligodeoxynucleotides was not statistically different from the control animals. In distinct contrast, animals treated for similar lengths of time with antisense c-myb oligodeoxynucleotides survived at least 3.5 times longer than the various control animals. In addition, animals receiving antisense c-myb DNA had significantly less disease at the two sites most frequently manifesting leukemic cell infiltration, the central nervous system and the ovary. These results suggest that phosphorothioate-modified antisense DNA may be efficacious for the treatment of human leukemia in vivo, and by analogy, for the treatment of other human neoplasias."} {"id": "PMID:1281546", "title": "Cell cycle-dependent changes in the organization of an intermediate filament-associated protein: correlation with phosphorylation by p34cdc2.", "content": "During mitosis in BHK-21 baby hamster kidney cells the hyperphosphorylation of the type III intermediate filament (IF) protein vimentin is accompanied by the disruption of the IF network into punctate, protofilamentous structures. In this study, the morphological and biochemical changes of IFAP 300, a 300-kDa IF-crossbridging protein, are examined during mitosis. Double-label immunofluorescence shows that the distribution of IFAP 300 coincides with the typical filamentous pattern displayed by vimentin in interphase cells, whereas in mitotic cells it is reorganized into a punctate, nonfilamentous pattern. Accompanying these latter morphological changes, IFAP 300 is phosphorylated at a unique, mitosis-specific site. Comparison of the sites phosphorylated in cultured cells with those phosphorylated in vitro by various kinases suggests that IFAP 300 is phosphorylated by the same two kinases that phosphorylate vimentin during mitosis. One of these is p34cdc2 protein kinase, which appears to be responsible for the phosphorylation of the mitosis-specific site. The other kinase phosphorylates IFAP 300 in vitro at a site that is also found in the protein immunoprecipitated from either mitotic or interphase cells. In contrast to vimentin, the phosphorylation levels of IFAP 300 are not obviously altered between interphase and mitosis. Our results show that IFAP 300 is a physiological substrate for p34cdc2 and that this kinase may be involved in the mitotic reorganization of IFAP 300 by phosphorylating a mitosis-specific site. Taken together with our previous results, this study suggests that the activation of p34cdc2 coordinates the mitotic reorganization of the vimentin IF network both by severing IF-IF connections mediated by IFAP 300 and by disassembling individual IFs into protofilaments.", "contents": "Cell cycle-dependent changes in the organization of an intermediate filament-associated protein: correlation with phosphorylation by p34cdc2. During mitosis in BHK-21 baby hamster kidney cells the hyperphosphorylation of the type III intermediate filament (IF) protein vimentin is accompanied by the disruption of the IF network into punctate, protofilamentous structures. In this study, the morphological and biochemical changes of IFAP 300, a 300-kDa IF-crossbridging protein, are examined during mitosis. Double-label immunofluorescence shows that the distribution of IFAP 300 coincides with the typical filamentous pattern displayed by vimentin in interphase cells, whereas in mitotic cells it is reorganized into a punctate, nonfilamentous pattern. Accompanying these latter morphological changes, IFAP 300 is phosphorylated at a unique, mitosis-specific site. Comparison of the sites phosphorylated in cultured cells with those phosphorylated in vitro by various kinases suggests that IFAP 300 is phosphorylated by the same two kinases that phosphorylate vimentin during mitosis. One of these is p34cdc2 protein kinase, which appears to be responsible for the phosphorylation of the mitosis-specific site. The other kinase phosphorylates IFAP 300 in vitro at a site that is also found in the protein immunoprecipitated from either mitotic or interphase cells. In contrast to vimentin, the phosphorylation levels of IFAP 300 are not obviously altered between interphase and mitosis. Our results show that IFAP 300 is a physiological substrate for p34cdc2 and that this kinase may be involved in the mitotic reorganization of IFAP 300 by phosphorylating a mitosis-specific site. Taken together with our previous results, this study suggests that the activation of p34cdc2 coordinates the mitotic reorganization of the vimentin IF network both by severing IF-IF connections mediated by IFAP 300 and by disassembling individual IFs into protofilaments."} {"id": "PMID:1281547", "title": "Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus.", "content": "D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition.", "contents": "Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus. D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition."} {"id": "PMID:1281548", "title": "Nitric oxide synthase in macula densa regulates glomerular capillary pressure.", "content": "Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission.", "contents": "Nitric oxide synthase in macula densa regulates glomerular capillary pressure. Tubular-fluid reabsorption by specialized cells of the nephron at the junction of the ascending limb of the loop of Henle and the distal convoluted tubule, termed the macula densa, releases compounds causing vasoconstriction of the adjacent afferent arteriole. Activation of this tubuloglomerular feedback response reduces glomerular capillary pressure of the nephron and, hence, the glomerular filtration rate. The tubuloglomerular feedback response functions in a negative-feedback mode to relate glomerular capillary pressure to tubular-fluid delivery and reabsorption. This system has been implicated in renal autoregulation, renin release, and longterm body fluid and blood-pressure homeostasis. Here we report that arginine-derived nitric oxide, generated in the macula densa, is an additional intercellular signaling molecule that is released during tubular-fluid reabsorption and counters the vasoconstriction of the afferent arteriole. Antibody to rat cerebellar constitutive nitric oxide synthase stained rat macula densa cells specifically. Microperfusion of the macula densa segment of single nephrons with N omega-methyl-L-arginine (an inhibitor of nitric oxide synthase) or with pyocyanin (a lipid-soluble inhibitor of endothelium-derived relaxation factor) showed that generation of nitric oxide can vasodilate the afferent arteriole and increase glomerular capillary pressure; this effect was blocked by drugs that prevent tubular-fluid reabsorption. We conclude that nitric oxide synthase in macula densa cells is activated by tubular-fluid reabsorption and mediates a vasodilating component to the tubuloglomerular feedback response. These findings imply a role for arginine-derived nitric oxide in body fluid-volume and blood-pressure homeostasis, in addition to its established roles in modulation of vascular tone by the endothelium and in neurotransmission."} {"id": "PMID:1281549", "title": "Expression cloning of a human dual-specificity phosphatase.", "content": "Using an expression cloning strategy, we isolated a cDNA encoding a human protein-tyrosine-phosphatase. Bacteria expressing the kinase domain of the keratinocyte growth factor receptor (bek/fibroblast growth factor receptor 2) were infected with a fibroblast cDNA library in a phagemid prokaryotic expression vector and screened with a monoclonal anti-phosphotyrosine antibody. Among several clones showing decreased anti-phosphotyrosine recognition, one displayed phosphatase activity toward the kinase in vitro. The 4.1-kilobase cDNA encoded a deduced protein of 185 amino acids with limited sequence similarity to the vaccinia virus phosphatase VH1. The purified recombinant protein dephosphorylated several activated growth factor receptors, as well as serine-phosphorylated casein, in vitro. Both serine and tyrosine phosphatase activities were completely abolished by mutagenesis of a single cysteine residue conserved in VH1 and the VH1-related (VHR) human protein. These properties suggest that VHR is capable of regulating intracellular events mediated by both tyrosine and serine phosphorylation.", "contents": "Expression cloning of a human dual-specificity phosphatase. Using an expression cloning strategy, we isolated a cDNA encoding a human protein-tyrosine-phosphatase. Bacteria expressing the kinase domain of the keratinocyte growth factor receptor (bek/fibroblast growth factor receptor 2) were infected with a fibroblast cDNA library in a phagemid prokaryotic expression vector and screened with a monoclonal anti-phosphotyrosine antibody. Among several clones showing decreased anti-phosphotyrosine recognition, one displayed phosphatase activity toward the kinase in vitro. The 4.1-kilobase cDNA encoded a deduced protein of 185 amino acids with limited sequence similarity to the vaccinia virus phosphatase VH1. The purified recombinant protein dephosphorylated several activated growth factor receptors, as well as serine-phosphorylated casein, in vitro. Both serine and tyrosine phosphatase activities were completely abolished by mutagenesis of a single cysteine residue conserved in VH1 and the VH1-related (VHR) human protein. These properties suggest that VHR is capable of regulating intracellular events mediated by both tyrosine and serine phosphorylation."} {"id": "PMID:1281550", "title": "Transcription of the tumor necrosis factor alpha gene is rapidly induced by anti-immunoglobulin and blocked by cyclosporin A and FK506 in human B cells.", "content": "The human tumor necrosis factor alpha (TNF-alpha) gene encodes a cytokine whose activities have been implicated in many immunopathological processes, including the activation and differentiation of lymphocytes. Originally identified as a monocyte factor, our studies and those of others have demonstrated that B and T lymphocytes produce TNF-alpha when stimulated by a variety of inducers. We report here that TNF-alpha gene transcription is rapidly and highly induced in three independently derived human Burkitt lymphoma cell lines, as well as in freshly isolated human splenic B cells, activated by antibodies to surface immunoglobulin. This burst in TNF-alpha gene transcription is associated with an induction of TNF-alpha bioactivity in the culture supernatants from stimulated splenic B cells. Moreover, induction of TNF-alpha gene transcription by anti-immunoglobulin was blocked by the immunosuppressants cyclosporin A and FK506. These studies demonstrate that TNF-alpha production is an early event in B-cell activation and they establish the efficacy of using immunosuppressants as probes in dissecting transcriptional activation pathways in human B cells.", "contents": "Transcription of the tumor necrosis factor alpha gene is rapidly induced by anti-immunoglobulin and blocked by cyclosporin A and FK506 in human B cells. The human tumor necrosis factor alpha (TNF-alpha) gene encodes a cytokine whose activities have been implicated in many immunopathological processes, including the activation and differentiation of lymphocytes. Originally identified as a monocyte factor, our studies and those of others have demonstrated that B and T lymphocytes produce TNF-alpha when stimulated by a variety of inducers. We report here that TNF-alpha gene transcription is rapidly and highly induced in three independently derived human Burkitt lymphoma cell lines, as well as in freshly isolated human splenic B cells, activated by antibodies to surface immunoglobulin. This burst in TNF-alpha gene transcription is associated with an induction of TNF-alpha bioactivity in the culture supernatants from stimulated splenic B cells. Moreover, induction of TNF-alpha gene transcription by anti-immunoglobulin was blocked by the immunosuppressants cyclosporin A and FK506. These studies demonstrate that TNF-alpha production is an early event in B-cell activation and they establish the efficacy of using immunosuppressants as probes in dissecting transcriptional activation pathways in human B cells."} {"id": "PMID:1281551", "title": "Action to avoid an unnecessary outcome. Identifying iron deficiency in children.", "content": "Although mainly associated with anaemia, there are several other physical and psychological manifestations of iron deficiency. Awareness of community screening programmes would do much to reduce the incidence of this problem.", "contents": "Action to avoid an unnecessary outcome. Identifying iron deficiency in children. Although mainly associated with anaemia, there are several other physical and psychological manifestations of iron deficiency. Awareness of community screening programmes would do much to reduce the incidence of this problem."} {"id": "PMID:1281552", "title": "Tumor markers.", "content": "The past decade has seen many advances in the detection, characterization, and clinical applications of tumor markers. Although cancer screening applications have been limited by low disease prevalences in asymptomatic populations, tumor markers may be of diagnostic value in specific situations. The major use of tumor markers in primary care is in monitoring disease recurrence and the response to therapy. These uses may obviate the need for second-look surgery as it has with CA 125 elevations in ovarian carcinoma. On the other hand, tumor markers may indicate a need for second-look surgery as when CEA levels are elevated in colorectal carcinoma. Despite the apparent usefulness of markers in detecting cancer recurrence, the clinician is reminded of the conditions justifying treatment with the discovery of an abnormal laboratory value as put forth by Fries and Holman: (1) the treatment should be known to be effective, (2) early treatment should be known to be more effective than therapy given after the disease is clinically apparent (or early treatment carry the risk of less toxicity), and (3) prediction of impending deterioration must be consistently accurate. When these criteria are met, the planning of therapeutic regimens on the basis of marker levels may be rationally considered. Until these criteria are met, elevated markers can only stimulate the clinician to be more vigilant in the search for response to therapy or recurrence. Exciting developments are on the horizon with respect to the use of tumor markers in radionuclide imaging, radioimmunoguided surgery, and development of drug delivery systems. Further research into the structure and function of these substances may provide further insights into the phenomena of malignant transformation, tumor invasion, metastasis, and the development of new therapeutic options. With new advances in molecular biology and with the identification of oncogenes, it may be possible in the future to detect mutant oncoproteins that are specific for early cancers and premalignant conditions. Delecting these oncoproteins may provide a basis for development of truly sensitive and specific markers that can be used to detect cancer at an early and curable stage.", "contents": "Tumor markers. The past decade has seen many advances in the detection, characterization, and clinical applications of tumor markers. Although cancer screening applications have been limited by low disease prevalences in asymptomatic populations, tumor markers may be of diagnostic value in specific situations. The major use of tumor markers in primary care is in monitoring disease recurrence and the response to therapy. These uses may obviate the need for second-look surgery as it has with CA 125 elevations in ovarian carcinoma. On the other hand, tumor markers may indicate a need for second-look surgery as when CEA levels are elevated in colorectal carcinoma. Despite the apparent usefulness of markers in detecting cancer recurrence, the clinician is reminded of the conditions justifying treatment with the discovery of an abnormal laboratory value as put forth by Fries and Holman: (1) the treatment should be known to be effective, (2) early treatment should be known to be more effective than therapy given after the disease is clinically apparent (or early treatment carry the risk of less toxicity), and (3) prediction of impending deterioration must be consistently accurate. When these criteria are met, the planning of therapeutic regimens on the basis of marker levels may be rationally considered. Until these criteria are met, elevated markers can only stimulate the clinician to be more vigilant in the search for response to therapy or recurrence. Exciting developments are on the horizon with respect to the use of tumor markers in radionuclide imaging, radioimmunoguided surgery, and development of drug delivery systems. Further research into the structure and function of these substances may provide further insights into the phenomena of malignant transformation, tumor invasion, metastasis, and the development of new therapeutic options. With new advances in molecular biology and with the identification of oncogenes, it may be possible in the future to detect mutant oncoproteins that are specific for early cancers and premalignant conditions. Delecting these oncoproteins may provide a basis for development of truly sensitive and specific markers that can be used to detect cancer at an early and curable stage."} {"id": "PMID:1281554", "title": "Interleukin-8 as a macrophage-derived mediator of angiogenesis.", "content": "Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine that is chemotactic for lymphocytes and neutrophils, is also angiogenic. Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells. Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha. An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity. These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair.", "contents": "Interleukin-8 as a macrophage-derived mediator of angiogenesis. Angiogenic factors produced by monocytes-macrophages are involved in the pathogenesis of chronic inflammatory disorders characterized by persistent angiogenesis. The possibility was tested that interleukin-8 (IL-8), which is a cytokine that is chemotactic for lymphocytes and neutrophils, is also angiogenic. Human recombinant IL-8 was potently angiogenic when implanted in the rat cornea and induced proliferation and chemotaxis of human umbilical vein endothelial cells. Angiogenic activity present in the conditioned media of inflamed human rheumatoid synovial tissue macrophages or lipopolysaccharide-stimulated blood monocytes was equally blocked by antibodies to either IL-8 or tumor necrosis factor-alpha. An IL-8 antisense oligonucleotide specifically blocked the production of monocyte-induced angiogenic activity. These data suggest a function for macrophage-derived IL-8 in angiogenesis-dependent disorders such as rheumatoid arthritis, tumor growth, and wound repair."} {"id": "PMID:1281555", "title": "Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein.", "content": "Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor). GAF is translocated to the nucleus and binds a DNA element, the gamma-activated site. Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha. The IFN-gamma-dependent activation of the 91-kilodalton DNA binding protein required cytoplasmic phosphorylation of the protein on tyrosine. The 113-kilodalton ISGF-3 protein that is phosphorylated in response to IFN-alpha was not phosphorylated nor translocated to the nucleus in response to IFN-gamma. Thus the two different ligands result in tyrosine phosphorylation of different combinations of latent cytoplasmic transcription factors that then act at different DNA binding sites.", "contents": "Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor). GAF is translocated to the nucleus and binds a DNA element, the gamma-activated site. Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha. The IFN-gamma-dependent activation of the 91-kilodalton DNA binding protein required cytoplasmic phosphorylation of the protein on tyrosine. The 113-kilodalton ISGF-3 protein that is phosphorylated in response to IFN-alpha was not phosphorylated nor translocated to the nucleus in response to IFN-gamma. Thus the two different ligands result in tyrosine phosphorylation of different combinations of latent cytoplasmic transcription factors that then act at different DNA binding sites."} {"id": "PMID:1281557", "title": "A clinicopathological and immunohistochemical study of osteofibrous dysplasia, differentiated adamantinoma, and adamantinoma of long bones.", "content": "A clinicopathological and immunohistochemical study of 12 cases of osteofibrous dysplasia (OFD), two cases of differentiated adamantinoma, and five cases of adamantinoma of long bones is presented. Although OFD and differentiated adamantinoma showed similar radiologic findings, differentiated adamantinoma was more likely to be a recurrent lesion than osteofibrous dysplasia and seemed to require a more extensive surgical procedure. Immunohistochemically, cytokeratin- and vimentin-positive cells were seen in both OFD and differentiated adamantinoma. The positive cells were scattered in the former, and were both scattered and nest-like in the latter. Both these lesions, however, were negative for epithelial membrane antigen. Excluding two cases of Ewing-like adamantinoma, the other three cases of adamantinoma were also positive for cytokeratin and vimentin. These results suggest that these three lesions share the same histogenetic origin. The two cases of Ewing-like adamantinoma differ from tibial adamantinoma in their radiological, histological and immunohistochemical aspects, and seem to constitute a distinct variant of adamantinoma with a different histogenesis.", "contents": "A clinicopathological and immunohistochemical study of osteofibrous dysplasia, differentiated adamantinoma, and adamantinoma of long bones. A clinicopathological and immunohistochemical study of 12 cases of osteofibrous dysplasia (OFD), two cases of differentiated adamantinoma, and five cases of adamantinoma of long bones is presented. Although OFD and differentiated adamantinoma showed similar radiologic findings, differentiated adamantinoma was more likely to be a recurrent lesion than osteofibrous dysplasia and seemed to require a more extensive surgical procedure. Immunohistochemically, cytokeratin- and vimentin-positive cells were seen in both OFD and differentiated adamantinoma. The positive cells were scattered in the former, and were both scattered and nest-like in the latter. Both these lesions, however, were negative for epithelial membrane antigen. Excluding two cases of Ewing-like adamantinoma, the other three cases of adamantinoma were also positive for cytokeratin and vimentin. These results suggest that these three lesions share the same histogenetic origin. The two cases of Ewing-like adamantinoma differ from tibial adamantinoma in their radiological, histological and immunohistochemical aspects, and seem to constitute a distinct variant of adamantinoma with a different histogenesis."} {"id": "PMID:1281559", "title": "Homing of CD8CD57 T lymphocytes into acutely rejected renal allografts.", "content": "This study compares the cellular events in excised rejected renal allografts (RKT), with concurrent data in the peripheral blood (PB) in the same patients. The kidney transplants were obtained from recipients after rejections crises that were refractory to treatment. Two-color flow cytometry data was used for quantitation of cell subset profiles and quantitation of the density of individual lymphocyte surface antigen(s). The level of CD3DR-positive T cells in RKT was significantly higher than in PB. This difference ranged from 3 to 19-fold increases. There was an even more pronounced increase in CD8CD57 cell subset levels in RKT versus PB. In parallel with these findings, there was a 15-fold greater mean density of the CD8CD57 markers on T cells in RKT, when compared with the same cells in PB. The density of CD8 and of DR markers on CD3+ cells was also significantly higher (4-fold in each instance) in RKT. These data point to a homing of CD8CD57 cells with corresponding increases in the density of these markers in acutely rejected renal allografts, with only a relative decrease of this cell subset in peripheral blood. The appearance of a high preponderance of CD8CD57 cells in the renal allograft at the time of a rejection crisis may constitute a particularly severe prognostic sign regarding the reversibility of the response after treatment with steroids and/or monoclonal antibodies.", "contents": "Homing of CD8CD57 T lymphocytes into acutely rejected renal allografts. This study compares the cellular events in excised rejected renal allografts (RKT), with concurrent data in the peripheral blood (PB) in the same patients. The kidney transplants were obtained from recipients after rejections crises that were refractory to treatment. Two-color flow cytometry data was used for quantitation of cell subset profiles and quantitation of the density of individual lymphocyte surface antigen(s). The level of CD3DR-positive T cells in RKT was significantly higher than in PB. This difference ranged from 3 to 19-fold increases. There was an even more pronounced increase in CD8CD57 cell subset levels in RKT versus PB. In parallel with these findings, there was a 15-fold greater mean density of the CD8CD57 markers on T cells in RKT, when compared with the same cells in PB. The density of CD8 and of DR markers on CD3+ cells was also significantly higher (4-fold in each instance) in RKT. These data point to a homing of CD8CD57 cells with corresponding increases in the density of these markers in acutely rejected renal allografts, with only a relative decrease of this cell subset in peripheral blood. The appearance of a high preponderance of CD8CD57 cells in the renal allograft at the time of a rejection crisis may constitute a particularly severe prognostic sign regarding the reversibility of the response after treatment with steroids and/or monoclonal antibodies."} {"id": "PMID:1281560", "title": "In situ expression of tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 receptors in renal allograft biopsies.", "content": "The production and release of cytokines and their receptors are of critical importance in mediating graft injury. In order to evaluate the expression of cytokines in renal allograft biopsies, we performed immunocytochemical studies to detect activated cells positive for TNF-alpha, IFN-gamma, and IL-2R, using an alkaline phosphatase anti-alkaline phosphatase technique (APAAP). Sixty-one biopsy specimens from renal transplant patients were analyzed and were classified according to both clinical and conventional morphological criteria. There was a significant correlation between the number of positive cells reactive with monoclonal antibodies directed against TNF-alpha, IFN-gamma, and IL-2R and the presence of acute cellular rejection. The mean number of infiltrating cells (cells/mm2) positive for TNF-alpha (9.2 +/- 1.1), IFN-gamma (6.7 +/- 1.7), and IL-2R (31.2 +/- 4.8) was significantly greater in acute cellular rejection episodes compared with nonrejecting kidneys (0.9 +/- 0.2, 1.2 +/- 0.4, and 8.8 +/- 2.9 positive cells/mm2 for TNF-alpha, IFN-gamma, and IL-2R, respectively). No significant expression of these cytokines was found in the majority of biopsies with chronic rejection. In two cases, in which acute cellular rejection was not sustained on clinical grounds but was diagnosed on histology, the expression of TNF-alpha, IFN-gamma, and IL-2R was similar to that observed in typical cellular rejection. We conclude that TNF-alpha, IFN-gamma, and IL-2R are markedly expressed by activated mononuclear infiltrating cells in acute cellular rejection, and that these cytokines play an important role in allograft rejection. The immunocytochemical evaluation of cytokine expression is a simple and rapid method that is helpful in differentiating acute cellular rejection from other causes of graft disfunction.", "contents": "In situ expression of tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 receptors in renal allograft biopsies. The production and release of cytokines and their receptors are of critical importance in mediating graft injury. In order to evaluate the expression of cytokines in renal allograft biopsies, we performed immunocytochemical studies to detect activated cells positive for TNF-alpha, IFN-gamma, and IL-2R, using an alkaline phosphatase anti-alkaline phosphatase technique (APAAP). Sixty-one biopsy specimens from renal transplant patients were analyzed and were classified according to both clinical and conventional morphological criteria. There was a significant correlation between the number of positive cells reactive with monoclonal antibodies directed against TNF-alpha, IFN-gamma, and IL-2R and the presence of acute cellular rejection. The mean number of infiltrating cells (cells/mm2) positive for TNF-alpha (9.2 +/- 1.1), IFN-gamma (6.7 +/- 1.7), and IL-2R (31.2 +/- 4.8) was significantly greater in acute cellular rejection episodes compared with nonrejecting kidneys (0.9 +/- 0.2, 1.2 +/- 0.4, and 8.8 +/- 2.9 positive cells/mm2 for TNF-alpha, IFN-gamma, and IL-2R, respectively). No significant expression of these cytokines was found in the majority of biopsies with chronic rejection. In two cases, in which acute cellular rejection was not sustained on clinical grounds but was diagnosed on histology, the expression of TNF-alpha, IFN-gamma, and IL-2R was similar to that observed in typical cellular rejection. We conclude that TNF-alpha, IFN-gamma, and IL-2R are markedly expressed by activated mononuclear infiltrating cells in acute cellular rejection, and that these cytokines play an important role in allograft rejection. The immunocytochemical evaluation of cytokine expression is a simple and rapid method that is helpful in differentiating acute cellular rejection from other causes of graft disfunction."} {"id": "PMID:1281558", "title": "[Single-fraction radiotherapy of painful bone metastases].", "content": "We analyzed first results obtained in 92 patients treated with single-dose fraction radiotherapy for painful bone metastases. Tumour doses was 10 Gy in a single fraction. Response was obtained in 59/92 (64%) patients. Thirty nine patients had complete response and 20 had partial response. Pain recurred in 18/39 patients who initially responded. Toxicity of this radiotherapeutic treatment is acceptable, and can easily be managed with standard therapy.", "contents": "[Single-fraction radiotherapy of painful bone metastases]. We analyzed first results obtained in 92 patients treated with single-dose fraction radiotherapy for painful bone metastases. Tumour doses was 10 Gy in a single fraction. Response was obtained in 59/92 (64%) patients. Thirty nine patients had complete response and 20 had partial response. Pain recurred in 18/39 patients who initially responded. Toxicity of this radiotherapeutic treatment is acceptable, and can easily be managed with standard therapy."} {"id": "PMID:1281561", "title": "The distinct effects of FK506 on the activation, proliferation, and differentiation of human B lymphocytes.", "content": "We examined the effect of FK506 on the activation, proliferation and differentiation of human B lymphocytes in vitro. FK506 inhibited the proliferative response of resting B cells induced by Staphylococcus aureus Cowan strain I (SAC) and phorbol myristate acetate (PMA) in a dose-dependent manner. Inhibition of cell proliferation by FK506 was caused by a selective block of G0 to G1 phase transition leading to cell arrest. In addition, the proliferative response of in vivo-activated B cells and lymphokine-driven B cell proliferation were also found to be sensitive to FK506. Interestingly, FK506 did not affect the expression of activation antigens such as CD23, IL-2 receptor (CD25), and transferrin receptor (CD71). Finally, FK506 had little effect on B cell antibody generation in a T cell-independent system. Conversely, FK506 suppressed neither proliferation nor immunoglobulin secretion in a human B lymphoblastoid cell line. These results indicate that FK506 has discrete effects on the different stages of the B cell maturation.", "contents": "The distinct effects of FK506 on the activation, proliferation, and differentiation of human B lymphocytes. We examined the effect of FK506 on the activation, proliferation and differentiation of human B lymphocytes in vitro. FK506 inhibited the proliferative response of resting B cells induced by Staphylococcus aureus Cowan strain I (SAC) and phorbol myristate acetate (PMA) in a dose-dependent manner. Inhibition of cell proliferation by FK506 was caused by a selective block of G0 to G1 phase transition leading to cell arrest. In addition, the proliferative response of in vivo-activated B cells and lymphokine-driven B cell proliferation were also found to be sensitive to FK506. Interestingly, FK506 did not affect the expression of activation antigens such as CD23, IL-2 receptor (CD25), and transferrin receptor (CD71). Finally, FK506 had little effect on B cell antibody generation in a T cell-independent system. Conversely, FK506 suppressed neither proliferation nor immunoglobulin secretion in a human B lymphoblastoid cell line. These results indicate that FK506 has discrete effects on the different stages of the B cell maturation."} {"id": "PMID:1281562", "title": "FK506-induced kidney tubular cell injury.", "content": "Some renal changes associated with cyclosporine, such as tubular vacuolization and glomerular thrombosis, have also been reported with FK506. Furthermore, FK506 therapy is associated with a decrease in glomerular filtration rate and renal plasma flow and an increase in renal vascular resistance. We studied the in vitro tubular cell sensitivity to FK506 in comparison with CsA, the ultrastructural changes induced by FK506 and CsA, and the effect of both drugs on tubular cell growth in vitro. We also investigated whether FK506 and CsA induced endothelin-1 (ET-1) secretion of cultured tubular cells and whether this stimulatory effect coincided with a change in the endothelin systemic synthesis. Exposure of tubular cells to high concentrations of FK506 or CsA (10, 50, 100 microM) induced a time- and dose-dependent cell injury in vitro. The damage induced by FK506 and CsA was characterized by a direct cytotoxic effect on tubular cells, as expressed by release of 3H thymidine from prelabeled cells, N-acetyl-beta-D-glucosaminidase release, and cell detachment. Ultrastructural changes (vacuolizations, swelling, and mitochondrial enlargement) and inhibition of the growth of cultured tubular cells were also observed at high concentrations of FK506 and CsA. Low concentrations of FK506 and CsA (1, 0.1, 0.01, 0.001 microM) were not cytotoxic and induced only a minimal inhibitory effect on the growth of tubular cells in vitro. We demonstrated that FK506 (1, 0.1, 0.01 microM) time-dependently stimulated the secretion of endothelin by cultured tubular cells. CsA 10, 1, 0.1, 0.01 also exerted an enhancing effect on ET-1 secretion in cultured tubular cells. We observed that the concentration of CsA that induced the most important enhancing effect was 10 or 100 times higher than that required for FK506 to observe the same effect. The concentrations of FK506 or CsA that induced ET-1 secretion were not cytolytic for tubular cells in vitro. FK506- or CsA-treated rats showed an increase in serum level of ET-1 in comparison with the control. Through the stimulatory effect on endothelin secretion by tubular cells, FK506 and CsA may induce a perturbation of renal hemodynamics. Concentrations of FK506 and CsA, higher than established serum levels but close to those reached in tissues, are cytotoxic for tubular cells and induced ultrastructural changes and a significant delayed regeneration.", "contents": "FK506-induced kidney tubular cell injury. Some renal changes associated with cyclosporine, such as tubular vacuolization and glomerular thrombosis, have also been reported with FK506. Furthermore, FK506 therapy is associated with a decrease in glomerular filtration rate and renal plasma flow and an increase in renal vascular resistance. We studied the in vitro tubular cell sensitivity to FK506 in comparison with CsA, the ultrastructural changes induced by FK506 and CsA, and the effect of both drugs on tubular cell growth in vitro. We also investigated whether FK506 and CsA induced endothelin-1 (ET-1) secretion of cultured tubular cells and whether this stimulatory effect coincided with a change in the endothelin systemic synthesis. Exposure of tubular cells to high concentrations of FK506 or CsA (10, 50, 100 microM) induced a time- and dose-dependent cell injury in vitro. The damage induced by FK506 and CsA was characterized by a direct cytotoxic effect on tubular cells, as expressed by release of 3H thymidine from prelabeled cells, N-acetyl-beta-D-glucosaminidase release, and cell detachment. Ultrastructural changes (vacuolizations, swelling, and mitochondrial enlargement) and inhibition of the growth of cultured tubular cells were also observed at high concentrations of FK506 and CsA. Low concentrations of FK506 and CsA (1, 0.1, 0.01, 0.001 microM) were not cytotoxic and induced only a minimal inhibitory effect on the growth of tubular cells in vitro. We demonstrated that FK506 (1, 0.1, 0.01 microM) time-dependently stimulated the secretion of endothelin by cultured tubular cells. CsA 10, 1, 0.1, 0.01 also exerted an enhancing effect on ET-1 secretion in cultured tubular cells. We observed that the concentration of CsA that induced the most important enhancing effect was 10 or 100 times higher than that required for FK506 to observe the same effect. The concentrations of FK506 or CsA that induced ET-1 secretion were not cytolytic for tubular cells in vitro. FK506- or CsA-treated rats showed an increase in serum level of ET-1 in comparison with the control. Through the stimulatory effect on endothelin secretion by tubular cells, FK506 and CsA may induce a perturbation of renal hemodynamics. Concentrations of FK506 and CsA, higher than established serum levels but close to those reached in tissues, are cytotoxic for tubular cells and induced ultrastructural changes and a significant delayed regeneration."} {"id": "PMID:1281563", "title": "Heterogeneity in the anti-HLA-DR immune response elicited by the antiidiotypic monoclonal antibody F5-444. Analysis at the clonal level.", "content": "A total of 630 hybridomas were generated from a BALB/c mouse immunized with the anti-id mAb F5-444, which binds an idiotope within the antigen-combining site of mAb AC1.59. The latter recognizes a determinant shared by HLA-DR1, DRw8, DR9 antigens and subtypes of HLA-DR4 and DR6 that is poorly expressed by HLA-DRw16 and DRw17 antigens. Eight anti-anti-id mAb were shown with serological and immunochemical assays to react with HLA-DR antigens. Detailed analysis of these anti-HLA-DR anti-anti-id mAb showed that they differ from the original anti-HLA-DR mAb AC1.59 and among themselves in either isotype, fine specificity, extent of reactivity with the nominal antigen, differential reactivity with soluble or cell-bound antigen, and/or idiotype profile. These observations emphasize the need to characterize a panel of antigen-binding anti-anti-id mAb in order to evaluate the degree of similarity existing between antigen-binding antibodies induced by an anti-id mAb and the original antigen-binding mAb.", "contents": "Heterogeneity in the anti-HLA-DR immune response elicited by the antiidiotypic monoclonal antibody F5-444. Analysis at the clonal level. A total of 630 hybridomas were generated from a BALB/c mouse immunized with the anti-id mAb F5-444, which binds an idiotope within the antigen-combining site of mAb AC1.59. The latter recognizes a determinant shared by HLA-DR1, DRw8, DR9 antigens and subtypes of HLA-DR4 and DR6 that is poorly expressed by HLA-DRw16 and DRw17 antigens. Eight anti-anti-id mAb were shown with serological and immunochemical assays to react with HLA-DR antigens. Detailed analysis of these anti-HLA-DR anti-anti-id mAb showed that they differ from the original anti-HLA-DR mAb AC1.59 and among themselves in either isotype, fine specificity, extent of reactivity with the nominal antigen, differential reactivity with soluble or cell-bound antigen, and/or idiotype profile. These observations emphasize the need to characterize a panel of antigen-binding anti-anti-id mAb in order to evaluate the degree of similarity existing between antigen-binding antibodies induced by an anti-id mAb and the original antigen-binding mAb."} {"id": "PMID:1281565", "title": "Induction of long-term survival of rat skin allografts by a novel, highly efficient anti-CD4 monoclonal antibody.", "content": "The new monoclonal antirat CD4 antibody RIB 5/2, which detects another epitope than those covered by W3/25 and MRC OX35, was tested for its immunosuppressive potency following skin allografting by using strain combinations with different genetic barriers in the MHC and genetic low- or high-responder background. High-dose and long-term therapy of the grafted rats led to a significant delay of the acute rejection (P < 0.01) in the strain combination Wistar Furth-to-BDX as well as in LEW1W-to-LEW1A. No significant prolongation of the mean allograft survival time was obtained for the high-responder rats (LEW1A-to-LEW1W). Cytofluorometric analysis revealed that RIB 5/2 exerts the immunosuppressive activity predominantly by modulation of the CD4 glycoprotein. Furthermore, the dependence of the humoral immune response against the mouse-globulins upon the administered protein quantity could be demonstrated.", "contents": "Induction of long-term survival of rat skin allografts by a novel, highly efficient anti-CD4 monoclonal antibody. The new monoclonal antirat CD4 antibody RIB 5/2, which detects another epitope than those covered by W3/25 and MRC OX35, was tested for its immunosuppressive potency following skin allografting by using strain combinations with different genetic barriers in the MHC and genetic low- or high-responder background. High-dose and long-term therapy of the grafted rats led to a significant delay of the acute rejection (P < 0.01) in the strain combination Wistar Furth-to-BDX as well as in LEW1W-to-LEW1A. No significant prolongation of the mean allograft survival time was obtained for the high-responder rats (LEW1A-to-LEW1W). Cytofluorometric analysis revealed that RIB 5/2 exerts the immunosuppressive activity predominantly by modulation of the CD4 glycoprotein. Furthermore, the dependence of the humoral immune response against the mouse-globulins upon the administered protein quantity could be demonstrated."} {"id": "PMID:1281566", "title": "Prolongation of graft survival in primate allograft transplantation by yttrium-90-labeled anti-Tac in conjunction with granulocyte colony-stimulating factor.", "content": "High-affinity IL-2 receptors are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac, a murine monoclonal antibody specific for the IL-2R alpha subunit, was used to inhibit organ allograft rejection. To enhance its effector function, anti-Tac was armed by chelation with yttrium-90, a pure beta-emitting radionuclide. Animals received no immunosuppression (n = 5, group I, controls), unmodified anti-Tac (n = 5, 1 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 1.6 mCi/kg divided into four doses, group III). The animals in group IV (n = 4) were treated identically to those in group III with the exception that 5 micrograms/kg/dose of granulocyte colony-stimulating factor was administered intramuscularly on the days when the yttrium-90 was given and on postoperative days 12 through 35 in order to reduce hematopoietic toxicity. Mean graft survival +/- S.E.M. for the control group was 8.2 +/- 0.5 days as compared with 13.8 +/- 2.1 days (P < 0.05) for those monkeys treated with unmodified anti-Tac. Graft survival was further prolonged in animals of group III that received 90Y-anti-Tac, with a mean graft survival of 45.0 +/- 11.8 days; however, three of the five monkeys retained viable grafts within this group but died secondary to bone marrow suppression. In comparison, the monkeys in group IV that were treated with G-CSF in conjunction with 90Y-anti-Tac had a mean graft survival of 49.2 +/- 2.9 days. In contrast to group III there were no deaths in the group (IV) receiving G-CSF. Furthermore, animals in group IV had a reduced magnitude and shortened duration of irradiation-induced neutropenia when compared with that observed in group III animals that did not receive G-CSF. Thus, treatment with 90Y-anti-Tac in conjunction with G-CSF may have potential applications in organ transplantation and the treatment of IL-2 receptor-expressing neoplastic diseases.", "contents": "Prolongation of graft survival in primate allograft transplantation by yttrium-90-labeled anti-Tac in conjunction with granulocyte colony-stimulating factor. High-affinity IL-2 receptors are expressed by T cells activated in response to foreign histocompatibility antigens but not by normal resting T cells. To exploit this difference in IL-2R expression, anti-Tac, a murine monoclonal antibody specific for the IL-2R alpha subunit, was used to inhibit organ allograft rejection. To enhance its effector function, anti-Tac was armed by chelation with yttrium-90, a pure beta-emitting radionuclide. Animals received no immunosuppression (n = 5, group I, controls), unmodified anti-Tac (n = 5, 1 mg/kg q.o.d., group II), or 90Y-anti-Tac (n = 5, 1.6 mCi/kg divided into four doses, group III). The animals in group IV (n = 4) were treated identically to those in group III with the exception that 5 micrograms/kg/dose of granulocyte colony-stimulating factor was administered intramuscularly on the days when the yttrium-90 was given and on postoperative days 12 through 35 in order to reduce hematopoietic toxicity. Mean graft survival +/- S.E.M. for the control group was 8.2 +/- 0.5 days as compared with 13.8 +/- 2.1 days (P < 0.05) for those monkeys treated with unmodified anti-Tac. Graft survival was further prolonged in animals of group III that received 90Y-anti-Tac, with a mean graft survival of 45.0 +/- 11.8 days; however, three of the five monkeys retained viable grafts within this group but died secondary to bone marrow suppression. In comparison, the monkeys in group IV that were treated with G-CSF in conjunction with 90Y-anti-Tac had a mean graft survival of 49.2 +/- 2.9 days. In contrast to group III there were no deaths in the group (IV) receiving G-CSF. Furthermore, animals in group IV had a reduced magnitude and shortened duration of irradiation-induced neutropenia when compared with that observed in group III animals that did not receive G-CSF. Thus, treatment with 90Y-anti-Tac in conjunction with G-CSF may have potential applications in organ transplantation and the treatment of IL-2 receptor-expressing neoplastic diseases."} {"id": "PMID:1281567", "title": "Identification of natural suppressor cells in long-term renal allograft recipients.", "content": "We have previously reported an abnormal expansion of CD3+Leu7+ (CD57+) large granular lymphocytes in long-term renal allograft recipients. These cells lacked NK activity, T-helper activity and did not respond to T cell mitogens. The following studies were done in order to further define the functional characteristics of these cells. We sorted CD3+Leu7+ T cells from the peripheral blood of 45 recipients (all with good renal allograft function), and found that these cells suppress mixed lymphocyte culture responses and pokeweed mitogen-induced IgG secretion in a non-genetically restricted manner. PWM-induced IgG secretion assays are suppressed by 60-100%, and MLC responses are suppressed by 20-85% at a ratio of 1:10 CD3+Leu7+ cells to responder/effector cells. Supernatants from CD3+Leu7+ cell cultures are also suppressive. On the other hand, unsorted cells and non-CD3+Leu7+ sorted cells either enhance responses or produce less than 10% suppression under the same conditions. Patients who were tested more than once showed a relatively stable percentage and suppressive effect of their CD3+Leu7+ cells over an interval of 6-12 months. These nonspecifically suppressive CD3+Leu7+ large granular lymphocytes are similar in many ways to the natural suppressor cells that have been identified in hematopoietic tissues, in graft-vs.-host disease, and in the lymphoid organs of neonates.", "contents": "Identification of natural suppressor cells in long-term renal allograft recipients. We have previously reported an abnormal expansion of CD3+Leu7+ (CD57+) large granular lymphocytes in long-term renal allograft recipients. These cells lacked NK activity, T-helper activity and did not respond to T cell mitogens. The following studies were done in order to further define the functional characteristics of these cells. We sorted CD3+Leu7+ T cells from the peripheral blood of 45 recipients (all with good renal allograft function), and found that these cells suppress mixed lymphocyte culture responses and pokeweed mitogen-induced IgG secretion in a non-genetically restricted manner. PWM-induced IgG secretion assays are suppressed by 60-100%, and MLC responses are suppressed by 20-85% at a ratio of 1:10 CD3+Leu7+ cells to responder/effector cells. Supernatants from CD3+Leu7+ cell cultures are also suppressive. On the other hand, unsorted cells and non-CD3+Leu7+ sorted cells either enhance responses or produce less than 10% suppression under the same conditions. Patients who were tested more than once showed a relatively stable percentage and suppressive effect of their CD3+Leu7+ cells over an interval of 6-12 months. These nonspecifically suppressive CD3+Leu7+ large granular lymphocytes are similar in many ways to the natural suppressor cells that have been identified in hematopoietic tissues, in graft-vs.-host disease, and in the lymphoid organs of neonates."} {"id": "PMID:1281568", "title": "Enteral pancreatic enzyme feedback inhibition of the exocrine secretion of the human transplanted pancreas.", "content": "The mechanism of regulation of negative feedback inhibition of the exocrine pancreas and its possible role in decreasing the exocrine secretion of the grafted human pancreas is unknown. To evaluate this we studied the effect of oral pancreatic enzymes on the stimulated transplanted pancreatic exocrine secretion in eight patients with allograft pancreaticocystostomies. After an 8-hr fast, all graft exocrine secretions via graft stent, fistula, and urinary anastomosis were collected for a 1-hr basal period. A standard 300-ml Lundh test meal was then ingested, and all exocrine secretions were collected in 30-min intervals for 3 hr. This test was repeated with 6 capsules of pancrelipase (24,000 units of lipase, 120,000 units of amylase, and 150,000 units of protease) given with the Lundh test meal. Stent, urine and fistula volume, amylase, and pH were measured for each collection period. The total 3-hr amylase secreted after the test meal and the test meal plus pancrelipase were compared. The period of peak amylase secretion after the test meal alone was compared with the same period after the test meal plus pancrelipase and the premeal basal period. The total amylase decreased 34% from 5550 +/- 1000 to 3680 +/- 740 IU/3 hr (P < .03) with pancrelipase. The peak amylase secretion decreased 63% from 1520 +/- 271 to 567 +/- 185 IU/30 min (P < .02) with the addition of pancrelipase to the test meal. Pancrelipase eliminated all meal-stimulated amylase secretion with the mean secretion 16% below the basal secretion of 674 +/- 117 IU/30 min. We conclude that pancreatic negative feedback inhibition significantly decreases meal-stimulated and basal exocrine secretion in the transplanted human pancreas.", "contents": "Enteral pancreatic enzyme feedback inhibition of the exocrine secretion of the human transplanted pancreas. The mechanism of regulation of negative feedback inhibition of the exocrine pancreas and its possible role in decreasing the exocrine secretion of the grafted human pancreas is unknown. To evaluate this we studied the effect of oral pancreatic enzymes on the stimulated transplanted pancreatic exocrine secretion in eight patients with allograft pancreaticocystostomies. After an 8-hr fast, all graft exocrine secretions via graft stent, fistula, and urinary anastomosis were collected for a 1-hr basal period. A standard 300-ml Lundh test meal was then ingested, and all exocrine secretions were collected in 30-min intervals for 3 hr. This test was repeated with 6 capsules of pancrelipase (24,000 units of lipase, 120,000 units of amylase, and 150,000 units of protease) given with the Lundh test meal. Stent, urine and fistula volume, amylase, and pH were measured for each collection period. The total 3-hr amylase secreted after the test meal and the test meal plus pancrelipase were compared. The period of peak amylase secretion after the test meal alone was compared with the same period after the test meal plus pancrelipase and the premeal basal period. The total amylase decreased 34% from 5550 +/- 1000 to 3680 +/- 740 IU/3 hr (P < .03) with pancrelipase. The peak amylase secretion decreased 63% from 1520 +/- 271 to 567 +/- 185 IU/30 min (P < .02) with the addition of pancrelipase to the test meal. Pancrelipase eliminated all meal-stimulated amylase secretion with the mean secretion 16% below the basal secretion of 674 +/- 117 IU/30 min. We conclude that pancreatic negative feedback inhibition significantly decreases meal-stimulated and basal exocrine secretion in the transplanted human pancreas."} {"id": "PMID:1281586", "title": "Silver-binding nucleolar organizer regions in benign and malignant prostatic lesions.", "content": "Thirty-six transvesical or transurethral prostatectomy cases were selected from the histopathology files of the Laiko General Hospital. Among the 36 cases, there were 10 with benign prostatic hyperplasia (8 patients having distinct areas of adenosis) and 26 cases of prostatic adenocarcinoma (6 grade I, 13 grades II and III and 7 grade IV carcinomas). From each case, silver-binding nucleolar organizer regions (AgNORs) have been counted in sections of routinely processed paraffin-embedded tissue blocks. The mean AgNOR count per case was calculated. For the cases of prostatic hyperplasia, the mean AgNOR count was found to be 2.95 +/- 0.42, for adenosis 3.45 +/- 0.56, for grade I adenocarcinoma 4.97 +/- 0.74, for grades II and III 7.31 +/- 0.81 and for grade IV adenocarcinomas 11.41 +/- 1.68. This difference in the mean AgNOR count was found to be of statistical significance (p < 0.001) between adenosis and grade I adenocarcinomas and between grade II and III and grade IV adenocarcinomas. It appears that AgNOR counting may prove to be of benefit in differentiating between some benign and malignant prostatic lesions and that it might provide information concerning the biological behavior of prostatic adenocarcinomas.", "contents": "Silver-binding nucleolar organizer regions in benign and malignant prostatic lesions. Thirty-six transvesical or transurethral prostatectomy cases were selected from the histopathology files of the Laiko General Hospital. Among the 36 cases, there were 10 with benign prostatic hyperplasia (8 patients having distinct areas of adenosis) and 26 cases of prostatic adenocarcinoma (6 grade I, 13 grades II and III and 7 grade IV carcinomas). From each case, silver-binding nucleolar organizer regions (AgNORs) have been counted in sections of routinely processed paraffin-embedded tissue blocks. The mean AgNOR count per case was calculated. For the cases of prostatic hyperplasia, the mean AgNOR count was found to be 2.95 +/- 0.42, for adenosis 3.45 +/- 0.56, for grade I adenocarcinoma 4.97 +/- 0.74, for grades II and III 7.31 +/- 0.81 and for grade IV adenocarcinomas 11.41 +/- 1.68. This difference in the mean AgNOR count was found to be of statistical significance (p < 0.001) between adenosis and grade I adenocarcinomas and between grade II and III and grade IV adenocarcinomas. It appears that AgNOR counting may prove to be of benefit in differentiating between some benign and malignant prostatic lesions and that it might provide information concerning the biological behavior of prostatic adenocarcinomas."} {"id": "PMID:1281587", "title": "Treatment of castration-induced menopausal symptoms with low dose diethylstilbestrol in men with advanced prostate cancer.", "content": "Menopausal symptoms manifesting as hot flashes and sweats occur in up to 75 percent of patients following either orchiectomy or treatment with a luteinizing hormone-releasing hormone agonist for prostate cancer. As many as one third of these patients will experience symptoms severe enough to seek palliation. We treated 12 such patients with low dose diethylstilbestrol (1/3 mg daily). Nine patients demonstrated both objective and subjective improvement in their menopausal symptoms. Five patients experienced toxicity including new onset of gynecomastia or breast soreness although no patient discontinued treatment on this basis. No cardiovascular complications were noted. We conclude that low dose diethylstilbestrol is an inexpensive, effective means of controlling troublesome postorchiectomy menopausal symptoms in carefully selected patients.", "contents": "Treatment of castration-induced menopausal symptoms with low dose diethylstilbestrol in men with advanced prostate cancer. Menopausal symptoms manifesting as hot flashes and sweats occur in up to 75 percent of patients following either orchiectomy or treatment with a luteinizing hormone-releasing hormone agonist for prostate cancer. As many as one third of these patients will experience symptoms severe enough to seek palliation. We treated 12 such patients with low dose diethylstilbestrol (1/3 mg daily). Nine patients demonstrated both objective and subjective improvement in their menopausal symptoms. Five patients experienced toxicity including new onset of gynecomastia or breast soreness although no patient discontinued treatment on this basis. No cardiovascular complications were noted. We conclude that low dose diethylstilbestrol is an inexpensive, effective means of controlling troublesome postorchiectomy menopausal symptoms in carefully selected patients."} {"id": "PMID:1281588", "title": "Benign prostatic hyperplasia: appearance on magnetic resonance imaging.", "content": "Benign prostatic hyperplasia (BPH) has a variable appearance on magnetic resonance imaging (MRI). This study reviews and categorizes the MRI findings of this entity in a sample of 26 men. Cases where atypical or suspicious changes are incidental findings should be reported to the urologist for further investigation. In addition, familiarity with both the appearance of the normal prostate and the changes caused by BPH is necessary when staging patients with known prostate cancer.", "contents": "Benign prostatic hyperplasia: appearance on magnetic resonance imaging. Benign prostatic hyperplasia (BPH) has a variable appearance on magnetic resonance imaging (MRI). This study reviews and categorizes the MRI findings of this entity in a sample of 26 men. Cases where atypical or suspicious changes are incidental findings should be reported to the urologist for further investigation. In addition, familiarity with both the appearance of the normal prostate and the changes caused by BPH is necessary when staging patients with known prostate cancer."} {"id": "PMID:1281589", "title": "Humoral responses in rabbits immunized with two fractions of Haemonchus contortus: the antigen specificity of such antibodies.", "content": "Humoral responses were examined in rabbits immunized with either 28-40 kDa (Fraction 1) or a 19-24 kDa (Fraction 2) antigenic fraction from soluble antigens (Sol L3 Ag) from infective larvae (L3) of Haemonchus contortus. These fractions were eluted from electrophoretically separated Sol L3 Ag. Immunoblots revealed antibodies to Fraction 1 (fr. 1) or Fraction 2 (fr. 2) polypeptides as well as to several other molecular weight polypeptides of the Sol L3 Ag. The latter antibodies were shown by absorption studies not to be Sol L3 Ag cross-reactive anti-bacterial rabbit antibodies. When Sol L3 Ag was affinity-purified using monoclonal antibody to phosphorylcholine (PC) and the resulting fractions were further analysed by immunoblotting using rabbit anti fr. 1 or anti fr. 2 antiserum, the PC antigen was found to be shared between fr. 1 and other polypeptides of Sol L3 Ag. Using the rabbit antibody fractions eluted from nitrocellulose membranes containing fr. 1 or 2 polypeptides, it was found that these fractions contained antibody that bound mainly to fr. 1 and only to fr. 2 polypeptides of Sol L3 Ag. It is concluded that, from the present immune rabbit sera, antibodies specific for either fr. 1 or fr. 2 may be isolated and then used to purify small amounts of the corresponding antigens.", "contents": "Humoral responses in rabbits immunized with two fractions of Haemonchus contortus: the antigen specificity of such antibodies. Humoral responses were examined in rabbits immunized with either 28-40 kDa (Fraction 1) or a 19-24 kDa (Fraction 2) antigenic fraction from soluble antigens (Sol L3 Ag) from infective larvae (L3) of Haemonchus contortus. These fractions were eluted from electrophoretically separated Sol L3 Ag. Immunoblots revealed antibodies to Fraction 1 (fr. 1) or Fraction 2 (fr. 2) polypeptides as well as to several other molecular weight polypeptides of the Sol L3 Ag. The latter antibodies were shown by absorption studies not to be Sol L3 Ag cross-reactive anti-bacterial rabbit antibodies. When Sol L3 Ag was affinity-purified using monoclonal antibody to phosphorylcholine (PC) and the resulting fractions were further analysed by immunoblotting using rabbit anti fr. 1 or anti fr. 2 antiserum, the PC antigen was found to be shared between fr. 1 and other polypeptides of Sol L3 Ag. Using the rabbit antibody fractions eluted from nitrocellulose membranes containing fr. 1 or 2 polypeptides, it was found that these fractions contained antibody that bound mainly to fr. 1 and only to fr. 2 polypeptides of Sol L3 Ag. It is concluded that, from the present immune rabbit sera, antibodies specific for either fr. 1 or fr. 2 may be isolated and then used to purify small amounts of the corresponding antigens."} {"id": "PMID:1281590", "title": "Development and characterization of monoclonal antibodies to first-generation merozoites of Eimeria bovis.", "content": "Merozoites of Eimeria bovis were harvested from bovine monocyte cell cultures and used to immunize BALB/C mice. Spleens from immunized mice were removed and the cells fused with mouse myeloma cells. Supernates from resulting hybridoma cell lines were examined for antibodies to first-generation E. bovis merozoites using an indirect immunofluorescent antibody (IFA) assay. Three positive cell lines were identified and cloned by limiting dilution. All three cell lines produced immunoglobulins of the IgG1 isotype that recognized antigens in the anterior half to two-thirds of the merozoites. Specificity of the monoclonal antibodies was examined with the IFA assay against sporozoites of E. bovis, sporozoites and merozoites of Eimeria papillata from mice and Eimeria tenella from chickens, sporozoites of Isospora suis from pigs, and tachyzoites of Toxoplasma gondii and Neospora caninum from cell cultures. Monoclonal antibodies from the three clones reacted with the anterior end of E. bovis sporozoites, but did not react with the other parasites examined. None of the monoclonal antibodies reacted with merozoite antigens in immunoblots.", "contents": "Development and characterization of monoclonal antibodies to first-generation merozoites of Eimeria bovis. Merozoites of Eimeria bovis were harvested from bovine monocyte cell cultures and used to immunize BALB/C mice. Spleens from immunized mice were removed and the cells fused with mouse myeloma cells. Supernates from resulting hybridoma cell lines were examined for antibodies to first-generation E. bovis merozoites using an indirect immunofluorescent antibody (IFA) assay. Three positive cell lines were identified and cloned by limiting dilution. All three cell lines produced immunoglobulins of the IgG1 isotype that recognized antigens in the anterior half to two-thirds of the merozoites. Specificity of the monoclonal antibodies was examined with the IFA assay against sporozoites of E. bovis, sporozoites and merozoites of Eimeria papillata from mice and Eimeria tenella from chickens, sporozoites of Isospora suis from pigs, and tachyzoites of Toxoplasma gondii and Neospora caninum from cell cultures. Monoclonal antibodies from the three clones reacted with the anterior end of E. bovis sporozoites, but did not react with the other parasites examined. None of the monoclonal antibodies reacted with merozoite antigens in immunoblots."} {"id": "PMID:1281591", "title": "Specific alterations of the basement membrane and stroma antigens in human pituitary tumours in comparison with the normal anterior pituitary. An immunocytochemical study.", "content": "Our report is the first immunocytochemical study of the principal elements of the basement membrane (BM) and connective tissue in normal and adenomatous human anterior pituitaries. In normal tissues, both the parenchymatous BM limiting the endocrine cell cords and the endothelial BM around the capillaries were continuous and were stained with anti-laminin (LM), anti-type IV collagen (CIV) and anti-fibronectin (FN) antisera. Antiserum to type I collagen (CI) stained the connective tissue only. The same antigens were investigated in 23 human pituitary adenomas, 6 of them having been diagnosed as locally invasive by the radiologist and the neurosurgeon. In all cases a lack of cordal structure was observed and the parenchymatous BM was completely absent (9 cases) or fragmented (14 cases). No correlation could be established between the extent of parenchymatous BM alterations and the invasive behaviour of the tumour. In contrast, a continuous endothelial BM was observed around the blood vessels in all cases and its presence was confirmed in double immunofluorescence experiments using anti-von Willebrand factor and anti-LM or anti-CIV antisera. Anti-FN and CI also stained the wall of the vessels. The tumours showed arterial development, in addition to the capillaries found in normal tissue. The present results favour the hypothesis of a decreased synthesis of parenchymatous BM by human adenomatous pituitary cells in comparison with normal cells and show that these tumours are the site of an active arterial neovascularization.", "contents": "Specific alterations of the basement membrane and stroma antigens in human pituitary tumours in comparison with the normal anterior pituitary. An immunocytochemical study. Our report is the first immunocytochemical study of the principal elements of the basement membrane (BM) and connective tissue in normal and adenomatous human anterior pituitaries. In normal tissues, both the parenchymatous BM limiting the endocrine cell cords and the endothelial BM around the capillaries were continuous and were stained with anti-laminin (LM), anti-type IV collagen (CIV) and anti-fibronectin (FN) antisera. Antiserum to type I collagen (CI) stained the connective tissue only. The same antigens were investigated in 23 human pituitary adenomas, 6 of them having been diagnosed as locally invasive by the radiologist and the neurosurgeon. In all cases a lack of cordal structure was observed and the parenchymatous BM was completely absent (9 cases) or fragmented (14 cases). No correlation could be established between the extent of parenchymatous BM alterations and the invasive behaviour of the tumour. In contrast, a continuous endothelial BM was observed around the blood vessels in all cases and its presence was confirmed in double immunofluorescence experiments using anti-von Willebrand factor and anti-LM or anti-CIV antisera. Anti-FN and CI also stained the wall of the vessels. The tumours showed arterial development, in addition to the capillaries found in normal tissue. The present results favour the hypothesis of a decreased synthesis of parenchymatous BM by human adenomatous pituitary cells in comparison with normal cells and show that these tumours are the site of an active arterial neovascularization."} {"id": "PMID:1281592", "title": "Carcinosarcoma of the urinary bladder: a distinct variant characterized by small cell undifferentiated carcinoma with neuroendocrine features.", "content": "The clinicopathological features of two carcinosarcomas of the urinary bladder are reported. The tumours occurred in a 64- and a 66-year-old patient presenting with haematuria and both were polypoid. The epithelial component was consistent with small cell undifferentiated carcinoma with neuroendocrine differentiation, whereas the sarcomatous component did not display specific features. The carcinomatous component showed immunohistochemical reactivity for different epithelial markers as well as for chromogranin and neuron specific enolase. Conversely, the sarcomatous cells stained strongly for vimentin and in one case for muscle actin and smooth muscle actin. The differential diagnosis of biphasic tumours of the bladder is discussed and the literature reviewed.", "contents": "Carcinosarcoma of the urinary bladder: a distinct variant characterized by small cell undifferentiated carcinoma with neuroendocrine features. The clinicopathological features of two carcinosarcomas of the urinary bladder are reported. The tumours occurred in a 64- and a 66-year-old patient presenting with haematuria and both were polypoid. The epithelial component was consistent with small cell undifferentiated carcinoma with neuroendocrine differentiation, whereas the sarcomatous component did not display specific features. The carcinomatous component showed immunohistochemical reactivity for different epithelial markers as well as for chromogranin and neuron specific enolase. Conversely, the sarcomatous cells stained strongly for vimentin and in one case for muscle actin and smooth muscle actin. The differential diagnosis of biphasic tumours of the bladder is discussed and the literature reviewed."} {"id": "PMID:1281593", "title": "Differential uptake of systemic fluorochrome Hoechst 33342 in lung and liver metastasis of B16 melanoma.", "content": "The growth and vascularization patterns of B16 melanoma colonies in the liver and lungs were measured and compared by histological techniques and dye diffusion patterns after injection of the fluorochrome Hoechst 33342. In the liver, the fluorescent pattern of dye diffusion revealed that uninodular tumours measuring up to 146 microns in diameter were not functionally vascularized. However, when the nodules fused to give rise to multinodular tumours measuring between 256 and 366 microns in diameter, a reticular dye diffusion pattern revealed functional tumour vascularization. In the lungs, subpleural, parenchymal and peritubular (i.e. surrounding blood vessels and airways) tumours were observed. The two former classes were vascularized down to thicknesses and diameters of 49 and 24 microns respectively. In contrast, dye diffusion was never seen in peritubular tumour cuffs up to 609 microns in thickness. The results indicate differences in vascularization patterns in B16 tumours in the liver and lungs, and differences between tumours growing in different sites within the lungs. If these results are applicable to metastases in these two organs, they indicate potential diffusion-mediated resistance to chemotherapy, and potential hypoxia-mediated resistance to radiotherapy of both metastases and micrometastases.", "contents": "Differential uptake of systemic fluorochrome Hoechst 33342 in lung and liver metastasis of B16 melanoma. The growth and vascularization patterns of B16 melanoma colonies in the liver and lungs were measured and compared by histological techniques and dye diffusion patterns after injection of the fluorochrome Hoechst 33342. In the liver, the fluorescent pattern of dye diffusion revealed that uninodular tumours measuring up to 146 microns in diameter were not functionally vascularized. However, when the nodules fused to give rise to multinodular tumours measuring between 256 and 366 microns in diameter, a reticular dye diffusion pattern revealed functional tumour vascularization. In the lungs, subpleural, parenchymal and peritubular (i.e. surrounding blood vessels and airways) tumours were observed. The two former classes were vascularized down to thicknesses and diameters of 49 and 24 microns respectively. In contrast, dye diffusion was never seen in peritubular tumour cuffs up to 609 microns in thickness. The results indicate differences in vascularization patterns in B16 tumours in the liver and lungs, and differences between tumours growing in different sites within the lungs. If these results are applicable to metastases in these two organs, they indicate potential diffusion-mediated resistance to chemotherapy, and potential hypoxia-mediated resistance to radiotherapy of both metastases and micrometastases."} {"id": "PMID:1281594", "title": "Adrenocortical oncocytoma: case report with immunocytochemical and ultrastructural study.", "content": "An adrenocortical oncocytic neoplasm was detected incidentally in a 58-year-old man. The tumour weighted 315 g, showing haemorrhagic areas and broad fibrous bands. It was composed exclusively of large eosinophilic cells packed with mitochondria showing flat and infrequent tubulovesicular cristae and regression of steroid-related organelles. Occasional annulate lamellae and mitochondrial osmiophilic inclusions were present. Vimentin was diffusely expressed, whereas AE1/AE3 cytokeratin was detected in half of the cells; a focal punctate pattern of staining was exclusively observed for cytokeratin peptides 8 and 18. The patient had no evidence of disease 21 months after surgery.", "contents": "Adrenocortical oncocytoma: case report with immunocytochemical and ultrastructural study. An adrenocortical oncocytic neoplasm was detected incidentally in a 58-year-old man. The tumour weighted 315 g, showing haemorrhagic areas and broad fibrous bands. It was composed exclusively of large eosinophilic cells packed with mitochondria showing flat and infrequent tubulovesicular cristae and regression of steroid-related organelles. Occasional annulate lamellae and mitochondrial osmiophilic inclusions were present. Vimentin was diffusely expressed, whereas AE1/AE3 cytokeratin was detected in half of the cells; a focal punctate pattern of staining was exclusively observed for cytokeratin peptides 8 and 18. The patient had no evidence of disease 21 months after surgery."} {"id": "PMID:1281595", "title": "[The antigenic relationships of Morganella].", "content": "Interspecies relationships in the genus Morganella have been studied in the agglutination and adsorption tests. New data on the antigenic relationships of O groups O43 and O49 and more precise data on the antigenic relationships of O groups O1 to O42 have been obtained. For the first time the relationships of antigens 40 and 42 with 4, 35 and 31, 38 and 39, 9 and 45, 1a, d and 49; 45 and 47, 24 and 45; 5, 23, 26 with 47; 1, 19, 46 with 41, 48 have been described and the complete identity of O antigens 33 and 35; 34 and 36; 40 and 42; 3, 13 and 17 has been established. These data must be taken into consideration in the preparation of polyvalent agglutinating sera, necessary for finding out the serological picture of Morganella isolated from patients and the environment.", "contents": "[The antigenic relationships of Morganella]. Interspecies relationships in the genus Morganella have been studied in the agglutination and adsorption tests. New data on the antigenic relationships of O groups O43 and O49 and more precise data on the antigenic relationships of O groups O1 to O42 have been obtained. For the first time the relationships of antigens 40 and 42 with 4, 35 and 31, 38 and 39, 9 and 45, 1a, d and 49; 45 and 47, 24 and 45; 5, 23, 26 with 47; 1, 19, 46 with 41, 48 have been described and the complete identity of O antigens 33 and 35; 34 and 36; 40 and 42; 3, 13 and 17 has been established. These data must be taken into consideration in the preparation of polyvalent agglutinating sera, necessary for finding out the serological picture of Morganella isolated from patients and the environment."} {"id": "PMID:1281596", "title": "[The effect of the bronchoalveolar fluid of mice infected with the influenza virus on hematopoietic bone marrow precursors].", "content": "The influence of bronchoalveolar washing fluid (BAWF), as well as BAWF cells, obtained from mice infected with influenza virus, on the formation of exogenic spleen colony-forming units (CFUs) of lethally irradiated syngeneic recipients was studied. BAWF and BAWF cells of intact syngeneic mice stimulated the growth of CFUs. BAWF of mice infected with nonpathogenic strain A/PR/8/34 lost its capacity for stimulating the growth of colonies, and BAWF cells greatly suppressed colony formation in the spleen of recipients. The participation of interferon, colony-stimulating factor and the virus itself in the process of the modulation of colony formation is discussed.", "contents": "[The effect of the bronchoalveolar fluid of mice infected with the influenza virus on hematopoietic bone marrow precursors]. The influence of bronchoalveolar washing fluid (BAWF), as well as BAWF cells, obtained from mice infected with influenza virus, on the formation of exogenic spleen colony-forming units (CFUs) of lethally irradiated syngeneic recipients was studied. BAWF and BAWF cells of intact syngeneic mice stimulated the growth of CFUs. BAWF of mice infected with nonpathogenic strain A/PR/8/34 lost its capacity for stimulating the growth of colonies, and BAWF cells greatly suppressed colony formation in the spleen of recipients. The participation of interferon, colony-stimulating factor and the virus itself in the process of the modulation of colony formation is discussed."} {"id": "PMID:1281597", "title": "Immunohistochemical localization of alpha 2-macroglobulin receptors in human skin.", "content": "The localization of receptors for the proteinase inhibitor alpha 2-macroglobulin was studied in human skin by immunohistochemistry using a monoclonal mouse antibody. No epidermal staining was identified. alpha 2-Macroglobulin receptors were identified on dermal fibroblasts and dermal dendritic cells. Endothelial cells did not stain with the antibody, but positive staining cells were concentrated around dermal vessels. The myoepithelial layer of eccrine glands exhibited receptors; however, there was no staining of the eccrine epithelial layer. The distribution of alpha 2-macroglobulin receptors correlates with the reported distribution of alpha 2-macroglobulin: both are present in the dermal connective tissue and absent in epithelium and endothelium. The distribution of alpha 2-macroglobulin and its receptor in the dermis is consistent with a possible role in regulation of dermal proteolytic activity.", "contents": "Immunohistochemical localization of alpha 2-macroglobulin receptors in human skin. The localization of receptors for the proteinase inhibitor alpha 2-macroglobulin was studied in human skin by immunohistochemistry using a monoclonal mouse antibody. No epidermal staining was identified. alpha 2-Macroglobulin receptors were identified on dermal fibroblasts and dermal dendritic cells. Endothelial cells did not stain with the antibody, but positive staining cells were concentrated around dermal vessels. The myoepithelial layer of eccrine glands exhibited receptors; however, there was no staining of the eccrine epithelial layer. The distribution of alpha 2-macroglobulin receptors correlates with the reported distribution of alpha 2-macroglobulin: both are present in the dermal connective tissue and absent in epithelium and endothelium. The distribution of alpha 2-macroglobulin and its receptor in the dermis is consistent with a possible role in regulation of dermal proteolytic activity."} {"id": "PMID:1281598", "title": "A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia.", "content": "A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly in acute promyelocytic leukemia (M3). Eighteen cases of ANLL have been studied on admission, before chemotherapy was started. Levels of antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, plasminogen (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) and fibrinogen (Fg) were determined. The results showed normal levels of AT-III and PS, decreased levels of PC, alpha-2-AP, Pg and Fg in some cases, and an elevation of DD and T-AT III complex in almost all patients. There was a continuous evolution of data from M1 cases in which only slight alterations were seen up to M3 cases where all those pathologic data were observed.", "contents": "A continuous spectrum of hypercoagulability exists in acute nonlymphoblastic leukemia. A consumption coagulopathy syndrome has frequently been reported in association with some cases of acute nonlymphoblastic leukemia (ANLL) and mainly in acute promyelocytic leukemia (M3). Eighteen cases of ANLL have been studied on admission, before chemotherapy was started. Levels of antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (T-AT-III), tissue plasminogen activator, plasminogen (Pg), alpha-2-antiplasmin (alpha-2-AP), D-dimer (DD) and fibrinogen (Fg) were determined. The results showed normal levels of AT-III and PS, decreased levels of PC, alpha-2-AP, Pg and Fg in some cases, and an elevation of DD and T-AT III complex in almost all patients. There was a continuous evolution of data from M1 cases in which only slight alterations were seen up to M3 cases where all those pathologic data were observed."} {"id": "PMID:1281599", "title": "Effects of interleukin-3 and interleukin-6 on peripheral blood cells from multiple myeloma patients and their clinical significance.", "content": "The effects of interleukin-3 (IL-3) and interleukin-6 (IL-6) on nonadherent mononuclear cells (NMC) from the peripheral blood of 28 patients with multiple myeloma (MM), 3 patients with monoclonal gammopathy of undetermined significance (MGUS), and 3 normal controls were investigated. In 15 of 27 evaluable patients with MM, monoclonal-cytoplasmic-immunoglobulin (cIg)-positive plasma cells appeared from the T-cell-depleted NMC after 10 days of culture in the presence of IL-3 and IL-6. These changes were not observed in the T cell fraction of myeloma blood or in the T-cell-depleted NMC obtained from cases of MGUS or from normal controls. The percentage of cIg-positive plasmacytoid cells after 10 days of culture was significantly higher in the presence of both IL-3 and IL-6 than with each interleukin alone or the control medium. Furthermore, these changes were often observed in untreated patients. These findings suggest that myeloma precursor cells exist in the peripheral blood of MM patients, especially at diagnosis, and differentiate into cIg-positive cells in the presence of IL-3 and IL-6. This assay may be useful in discriminating the early stage of myeloma from MGUS.", "contents": "Effects of interleukin-3 and interleukin-6 on peripheral blood cells from multiple myeloma patients and their clinical significance. The effects of interleukin-3 (IL-3) and interleukin-6 (IL-6) on nonadherent mononuclear cells (NMC) from the peripheral blood of 28 patients with multiple myeloma (MM), 3 patients with monoclonal gammopathy of undetermined significance (MGUS), and 3 normal controls were investigated. In 15 of 27 evaluable patients with MM, monoclonal-cytoplasmic-immunoglobulin (cIg)-positive plasma cells appeared from the T-cell-depleted NMC after 10 days of culture in the presence of IL-3 and IL-6. These changes were not observed in the T cell fraction of myeloma blood or in the T-cell-depleted NMC obtained from cases of MGUS or from normal controls. The percentage of cIg-positive plasmacytoid cells after 10 days of culture was significantly higher in the presence of both IL-3 and IL-6 than with each interleukin alone or the control medium. Furthermore, these changes were often observed in untreated patients. These findings suggest that myeloma precursor cells exist in the peripheral blood of MM patients, especially at diagnosis, and differentiate into cIg-positive cells in the presence of IL-3 and IL-6. This assay may be useful in discriminating the early stage of myeloma from MGUS."} {"id": "PMID:1281600", "title": "DNA polymorphism in the beta-globin gene cluster in Saudi Arabs: relation to severity of sickle cell anaemia.", "content": "Significant DNA polymorphisms have been reported in the beta-globin gene cluster of epsilon-G gamma-A gamma-psi beta-delta-beta-gene region, in normal (Hb AA) individuals and in patients with sickle cell anaemia (SCA). Investigations of the extent of the DNA polymorphisms in the beta A- and beta S-globin gene cluster using Hind III, Hinc II, Ava II, Xmn I, and Hpa I, revealed several associations with mild SCA. The correlation of the presence (+) or absence (-) of the restriction endonuclease site to clinical severity in patients homozygous for beta S-gene showed that the mild form of SCA was associated mainly (> 90%) with the Xmn I polymorphic site 5' to G gamma, and to a lesser extent with Hinc II polymorphic site 5' to epsilon and in the psi beta-gene, with Hind III polymorphic site in G gamma and Hpa I polymorphic site 3' to the beta-globin gene, while in the severe form of SCA these polymorphic sites were absent in most patients. The polymorphism in the beta-globin gene cluster was significantly related to the expression of the beta S-gene and clinical severity of SCA.", "contents": "DNA polymorphism in the beta-globin gene cluster in Saudi Arabs: relation to severity of sickle cell anaemia. Significant DNA polymorphisms have been reported in the beta-globin gene cluster of epsilon-G gamma-A gamma-psi beta-delta-beta-gene region, in normal (Hb AA) individuals and in patients with sickle cell anaemia (SCA). Investigations of the extent of the DNA polymorphisms in the beta A- and beta S-globin gene cluster using Hind III, Hinc II, Ava II, Xmn I, and Hpa I, revealed several associations with mild SCA. The correlation of the presence (+) or absence (-) of the restriction endonuclease site to clinical severity in patients homozygous for beta S-gene showed that the mild form of SCA was associated mainly (> 90%) with the Xmn I polymorphic site 5' to G gamma, and to a lesser extent with Hinc II polymorphic site 5' to epsilon and in the psi beta-gene, with Hind III polymorphic site in G gamma and Hpa I polymorphic site 3' to the beta-globin gene, while in the severe form of SCA these polymorphic sites were absent in most patients. The polymorphism in the beta-globin gene cluster was significantly related to the expression of the beta S-gene and clinical severity of SCA."} {"id": "PMID:1281601", "title": "Heterogeneity and variation of clinical and haematological expression of haemoglobin S in Saudi Arabs.", "content": "Sickle cell haemoglobin (Hb S) occurs at a high frequency in the Eastern (EP), South-Western (SWP) and North-Western (NWP) Provinces of Saudi Arabia and the presentation of the Hb S is believed to exhibit clinical diversity in the different regions. Three areas of Saudi Arabia were screened to determine the frequency of Hb S and alpha- and beta-thalassaemias and glucose-6-phosphate dehydrogenase deficiency genes. Furthermore, in an attempt to investigate and compare the clinical and haematological presentation of sickle cell disease (SCD) in the different regions of Saudi Arabia, the individuals identified as Hb S homozygotes were investigated further. The patients were further classified on the basis of whether there was associated alpha- or beta-thalassaemia. A severity index (SI) was calculated for each patient and the clinical presentations and laboratory findings were compared. The results showed significantly variable severity of SCD in patients from different regions. The patients from the EP generally had a mild clinical presentation, while in the SWP and NWP majority of the patients suffered from a severe disease as judged by the SI. No correlation could be established between Hb F level and SI, though the WBC level correlated positively with the SI. The lowest SI values were encountered in patients with associated alpha-thalassaemia who also had the lowest WBC count and MCV and the highest RBC count and packed cell volume.", "contents": "Heterogeneity and variation of clinical and haematological expression of haemoglobin S in Saudi Arabs. Sickle cell haemoglobin (Hb S) occurs at a high frequency in the Eastern (EP), South-Western (SWP) and North-Western (NWP) Provinces of Saudi Arabia and the presentation of the Hb S is believed to exhibit clinical diversity in the different regions. Three areas of Saudi Arabia were screened to determine the frequency of Hb S and alpha- and beta-thalassaemias and glucose-6-phosphate dehydrogenase deficiency genes. Furthermore, in an attempt to investigate and compare the clinical and haematological presentation of sickle cell disease (SCD) in the different regions of Saudi Arabia, the individuals identified as Hb S homozygotes were investigated further. The patients were further classified on the basis of whether there was associated alpha- or beta-thalassaemia. A severity index (SI) was calculated for each patient and the clinical presentations and laboratory findings were compared. The results showed significantly variable severity of SCD in patients from different regions. The patients from the EP generally had a mild clinical presentation, while in the SWP and NWP majority of the patients suffered from a severe disease as judged by the SI. No correlation could be established between Hb F level and SI, though the WBC level correlated positively with the SI. The lowest SI values were encountered in patients with associated alpha-thalassaemia who also had the lowest WBC count and MCV and the highest RBC count and packed cell volume."} {"id": "PMID:1281602", "title": "Hb H disease caused by a homozygosity for the AATAAA-->AATAAG mutation in the polyadenylation site of the alpha 2-globin gene: hematological observations.", "content": "We have identified 7 patients with Hb H disease as homozygotes for a mutation in the polyadenylation site (AATAAA-->AATAAG) and have compared their hematological data with those of Hb H patients having other types of alpha-thalassemia determinants. All 7 patients exhibited moderate anemia with microcytosis and hypochromia being similar to that observed in the other patients. Relatives with a heterozygosity for this mutation are borderline microcytic and hypochromic without a significant anemia but with a low in vitro alpha/beta chain synthesis ratio. Analyses of the hemoglobin components identified low levels of Hb A2 and Hb H that were comparable to those found in other patients with Hb H disease; the level of the zeta-chain was low (average 0.14%).", "contents": "Hb H disease caused by a homozygosity for the AATAAA-->AATAAG mutation in the polyadenylation site of the alpha 2-globin gene: hematological observations. We have identified 7 patients with Hb H disease as homozygotes for a mutation in the polyadenylation site (AATAAA-->AATAAG) and have compared their hematological data with those of Hb H patients having other types of alpha-thalassemia determinants. All 7 patients exhibited moderate anemia with microcytosis and hypochromia being similar to that observed in the other patients. Relatives with a heterozygosity for this mutation are borderline microcytic and hypochromic without a significant anemia but with a low in vitro alpha/beta chain synthesis ratio. Analyses of the hemoglobin components identified low levels of Hb A2 and Hb H that were comparable to those found in other patients with Hb H disease; the level of the zeta-chain was low (average 0.14%)."} {"id": "PMID:1281603", "title": "Nucleolar organizer regions in malignant salivary gland tumors.", "content": "Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: mucoepidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoepidermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior.", "contents": "Nucleolar organizer regions in malignant salivary gland tumors. Proliferative activity of carcinomas arising from salivary glands was analyzed by enumeration of argyrophilic nucleolar organizer regions (AgNORs). The mean numbers of AgNORs in the various tumors were as follows: mucoepidermoid carcinoma, 2.20; acinic cell carcinoma, 2.51; adenoid cystic carcinoma (ACC), 2.57; carcinoma in pleomorphic adenoma, 1.00 (benign component) and 3.99 (cancer-bearing area); salivary duct carcinoma, 4.49; polymorphous low-grade adenocarcinoma, 3.37; sebaceous carcinoma, 2.57; oncocytic carcinoma, 4.63; adenocarcinoma, 4.53. Cells of most tumors showed heterogeneous activity within the same tumor. In mucoepidermoid carcinoma, the mucous cells had suppressed activity in comparison with the epidermoid cells and intermediate cells. In ACC, the activity of the tumor cells increased according to growth pattern in the order tubular, glandular and solid. In carcinoma in pleomorphic adenoma, vigorous proliferative activity was observed in the malignant component, whereas less active cells were seen in the myxoid or chondroid matrix. AgNOR staining was useful for distinguishing benign from malignant regions in carcinoma in pleomorphic adenoma. Our results suggest that mucoepidermoid carcinoma, acinic cell carcinoma and ACC, except for that with a solid growth pattern, may be considered as low-grade malignancies, whereas solid-type ACC, the cancer component in carcinoma in pleomorphic adenoma and some of the other carcinomas have high-grade malignant behavior."} {"id": "PMID:1281604", "title": "A histochemical study of acid phosphatases in medullary bone matrix and osteoclasts in laying Japanese quail.", "content": "Acid phosphatase activity in medullary bone matrix and osteoclasts of laying Japanese quail was examined histochemically. To avoid nonspecific staining, the reactivity of the enzyme was evaluated using both the azo dye method and the lead salt method and nonembedded thick sections and resin-embedded thin sections. The pH of the incubation medium was also varied from the acid range (pH 5.0 and 6.5) to the alkaline range (pH 8.5). Medullary bone osteoclasts contain both tartrate-resistant acid phosphatase (TRAP) activity and fluoride-resistant acid phosphatase (FRAP) activity, and no significant difference in intensity was detected between active and inactive osteoclasts. The entire matrix of medullary bone was positive for tartrate-resistant, fluoride-sensitive acid phosphatase activity. No reaction product was observed in sections incubated in substrate-free and pH 8.5 media. The results demonstrate the existence of FRAP in medullary bone osteoclasts and suggest that medullary bone matrix includes TRAP throughout the matrix.", "contents": "A histochemical study of acid phosphatases in medullary bone matrix and osteoclasts in laying Japanese quail. Acid phosphatase activity in medullary bone matrix and osteoclasts of laying Japanese quail was examined histochemically. To avoid nonspecific staining, the reactivity of the enzyme was evaluated using both the azo dye method and the lead salt method and nonembedded thick sections and resin-embedded thin sections. The pH of the incubation medium was also varied from the acid range (pH 5.0 and 6.5) to the alkaline range (pH 8.5). Medullary bone osteoclasts contain both tartrate-resistant acid phosphatase (TRAP) activity and fluoride-resistant acid phosphatase (FRAP) activity, and no significant difference in intensity was detected between active and inactive osteoclasts. The entire matrix of medullary bone was positive for tartrate-resistant, fluoride-sensitive acid phosphatase activity. No reaction product was observed in sections incubated in substrate-free and pH 8.5 media. The results demonstrate the existence of FRAP in medullary bone osteoclasts and suggest that medullary bone matrix includes TRAP throughout the matrix."} {"id": "PMID:1281605", "title": "Preparation and characterization of a mouse osteoclast-like multinucleated cell population.", "content": "We have reported that numerous tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated cells (TRAP+ MNCs) are formed when mouse osteoblastic cells and spleen cells are cocultured in the presence of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] (Endocrinology 123:2600, 1988). In this study, we prepared a TRAP+ MNC population using a modified coculture system and examined its osteoclastic properties. TRAP+ MNCs were formed in cocultures of mouse osteoblastic cells and marrow cells on 10 cm collagen gel-coated dishes. The TRAP+ MNC population was prepared by treating the dishes with 0.2% bacterial collagenase followed by density gradient centrifugation. The yield of TRAP+ MNCs was 20,000-40,000 cells per dish, much higher than that of osteoclasts (OCLs) isolated from neonatal rat bones (approximately 1000 cells per head). The purity of TRAP+ MNCs was 5.6 +/- 0.6% in cell number and about 30% in the number of nuclei. The recovery of TRAP+ MNCs after density gradient centrifugation was 30-40%. Acid production by MNCs was demonstrated by vital staining with acridine orange. Numerous resorption pits were formed when the MNC population was cultured for 48 h on bone slices. Autoradiography using [125I]salmon calcitonin (CT) showed abundant CT binding in most TRAP+ MNCs. Saturation analysis of [125I]salmon CT indicated a dissociation constant Kd for TRAP+ MNCs of 8.9 +/- 0.7 x 10(-10) M and 16.5 +/- 1.5 x 10(6) binding sites per cell. These results were similar to the Kd value (3.5 x 10(-10) M) and the number of binding sites (3.3 x 10(6) per cell) in isolated rat OCLs. Displacement curves for [125I]salmon CT with unlabeled salmon and human CT were similar in MNC and OCL preparations. Salmon and human CT increased cAMP production (maximal response: slmon CT at 10(-10) M, human CT at 10(-8) M; ED50s: salmon CT, 2.2 x 10(-11) M, human CT, 1.3 x 10(-9) M) in the MNC preparation. These results indicate that a large number of mouse TRAP+ MNCs possessing OCL characteristics can be easily prepared from in vitro cultures. This procedure will facilitate examination of mammalian OCL functions.", "contents": "Preparation and characterization of a mouse osteoclast-like multinucleated cell population. We have reported that numerous tartrate-resistant acid phosphatase-positive osteoclast-like multinucleated cells (TRAP+ MNCs) are formed when mouse osteoblastic cells and spleen cells are cocultured in the presence of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3] (Endocrinology 123:2600, 1988). In this study, we prepared a TRAP+ MNC population using a modified coculture system and examined its osteoclastic properties. TRAP+ MNCs were formed in cocultures of mouse osteoblastic cells and marrow cells on 10 cm collagen gel-coated dishes. The TRAP+ MNC population was prepared by treating the dishes with 0.2% bacterial collagenase followed by density gradient centrifugation. The yield of TRAP+ MNCs was 20,000-40,000 cells per dish, much higher than that of osteoclasts (OCLs) isolated from neonatal rat bones (approximately 1000 cells per head). The purity of TRAP+ MNCs was 5.6 +/- 0.6% in cell number and about 30% in the number of nuclei. The recovery of TRAP+ MNCs after density gradient centrifugation was 30-40%. Acid production by MNCs was demonstrated by vital staining with acridine orange. Numerous resorption pits were formed when the MNC population was cultured for 48 h on bone slices. Autoradiography using [125I]salmon calcitonin (CT) showed abundant CT binding in most TRAP+ MNCs. Saturation analysis of [125I]salmon CT indicated a dissociation constant Kd for TRAP+ MNCs of 8.9 +/- 0.7 x 10(-10) M and 16.5 +/- 1.5 x 10(6) binding sites per cell. These results were similar to the Kd value (3.5 x 10(-10) M) and the number of binding sites (3.3 x 10(6) per cell) in isolated rat OCLs. Displacement curves for [125I]salmon CT with unlabeled salmon and human CT were similar in MNC and OCL preparations. Salmon and human CT increased cAMP production (maximal response: slmon CT at 10(-10) M, human CT at 10(-8) M; ED50s: salmon CT, 2.2 x 10(-11) M, human CT, 1.3 x 10(-9) M) in the MNC preparation. These results indicate that a large number of mouse TRAP+ MNCs possessing OCL characteristics can be easily prepared from in vitro cultures. This procedure will facilitate examination of mammalian OCL functions."} {"id": "PMID:1281606", "title": "Effects of stem cell factor on osteoclast-like cell formation in long-term human marrow cultures.", "content": "Stem cell factor (SCF) is a newly described hematopoietic growth factor that stimulates the growth of primitive hematopoietic progenitors and mast cells. Since the osteoclast precursor is hematopoietic in origin, we tested SCF for its capacity to stimulate the formation of osteoclast-like multinucleated cells (MNC) in long-term human marrow cultures. These MNC express an osteoclast phenotype and form resorption lacunae on calcified matrices. Addition of SCF alone (0.1 pg/ml to 100 ng/ml) to long-term marrow cultures did not increase MNC formation. However, treatment of these cultures sequentially with SCF for 1 week followed by 1,25-(OH)2D3 for the second and third weeks of culture significantly enhanced MNC formation. [3H]Thymidine incorporation studies showed that SCF increased the proliferation of MNC precursors. These data suggested that SCF was acting on early MNC precursors. We then tested the capacity of SCF to stimulate the formation of colonies of committed precursors for osteoclast-like MNC. SCF (20 pg/ml to 20 ng/ml) enhanced osteoclast precursor formation in unfractionated bone marrow mononuclear cells but was unable to increase osteoclast precursor formation when a highly purified population of hematopoietic precursors was used as the target cells for SCF. These data suggest that SCF works in concert with other factors produced by nonhematopoietic marrow cells to increase the precursor pool for osteoclasts and that other factors, such as 1,25-(OH)2D3, complete the differentiation process to the mature osteoclast.", "contents": "Effects of stem cell factor on osteoclast-like cell formation in long-term human marrow cultures. Stem cell factor (SCF) is a newly described hematopoietic growth factor that stimulates the growth of primitive hematopoietic progenitors and mast cells. Since the osteoclast precursor is hematopoietic in origin, we tested SCF for its capacity to stimulate the formation of osteoclast-like multinucleated cells (MNC) in long-term human marrow cultures. These MNC express an osteoclast phenotype and form resorption lacunae on calcified matrices. Addition of SCF alone (0.1 pg/ml to 100 ng/ml) to long-term marrow cultures did not increase MNC formation. However, treatment of these cultures sequentially with SCF for 1 week followed by 1,25-(OH)2D3 for the second and third weeks of culture significantly enhanced MNC formation. [3H]Thymidine incorporation studies showed that SCF increased the proliferation of MNC precursors. These data suggested that SCF was acting on early MNC precursors. We then tested the capacity of SCF to stimulate the formation of colonies of committed precursors for osteoclast-like MNC. SCF (20 pg/ml to 20 ng/ml) enhanced osteoclast precursor formation in unfractionated bone marrow mononuclear cells but was unable to increase osteoclast precursor formation when a highly purified population of hematopoietic precursors was used as the target cells for SCF. These data suggest that SCF works in concert with other factors produced by nonhematopoietic marrow cells to increase the precursor pool for osteoclasts and that other factors, such as 1,25-(OH)2D3, complete the differentiation process to the mature osteoclast."} {"id": "PMID:1281607", "title": "Computerized immunoblot analyses (CIBA) of the distribution of prekallikrein and its activation products in vivo and in vitro.", "content": "The distribution of prekallikrein and the complexes of kallikrein with C1 inhibitor (C1INH), alpha 2-macroglobulin and approximately 58-kDa protein(s) (e.g. antithrombin III), differs in normal and C1INH-deficient human plasma, activated in vitro, due to different C1INH levels. Different distribution in the deficient plasma activated in vivo or in vitro, suggests different rates of complex clearance.", "contents": "Computerized immunoblot analyses (CIBA) of the distribution of prekallikrein and its activation products in vivo and in vitro. The distribution of prekallikrein and the complexes of kallikrein with C1 inhibitor (C1INH), alpha 2-macroglobulin and approximately 58-kDa protein(s) (e.g. antithrombin III), differs in normal and C1INH-deficient human plasma, activated in vitro, due to different C1INH levels. Different distribution in the deficient plasma activated in vivo or in vitro, suggests different rates of complex clearance."} {"id": "PMID:1281608", "title": "Determination of human low molecular weight kininogen by immunoassay.", "content": "It was the aim of the present investigation to develop a convenient method for determination of human kininogens. Using mono- and polyclonal antibody preparations an ELISA-system for specific determination of LMWK could be developed. In addition, the specificity of the monoclonal antibody suggests that their epitope in HMWK and its heavy chain is different to that in LMWK.", "contents": "Determination of human low molecular weight kininogen by immunoassay. It was the aim of the present investigation to develop a convenient method for determination of human kininogens. Using mono- and polyclonal antibody preparations an ELISA-system for specific determination of LMWK could be developed. In addition, the specificity of the monoclonal antibody suggests that their epitope in HMWK and its heavy chain is different to that in LMWK."} {"id": "PMID:1281609", "title": "Kininogen deficiency in the rat.", "content": "The Brown Norway Katholiek (B/N-Ka) strain rat is the only animal strain that demonstrates deficiency in plasma HMW- and LMW-kininogens with a low level of prekallikrein. We developed an RIA for rat HMW-kininogen, LMW-kininogen, and T-kininogen, and using them measured these proteins in B/N-Ka and normal strain (B/N-Ki) rats. Plasma level of immunoreactive as well as kinin-releasing HMW-kininogen and LMW-kininogen in B/N-Ka rats was either around 3% of their levels in the normal B/N-Ki rats. The cause of the plasma deficiency of kininogens in the B/N-Ka strain was examined by 35S-methionine uptake of primary cultures of hepatocytes from the B/N-Ki and B/N-Ka strains. The results indicated that the kininogens were synthesized in the B/N-Ka liver but not secreted into the medium. Northern blot analysis of poly A(+)RNA extracted from the livers of both strains demonstrated that the band corresponding to mRNA of HMW-kininogen was present in the mRNA from B/N-Ka liver as well as in that from the B/N-Ki one. The band was similar in size and intensity in both cases. This result confirmed the data that immunoreactive HMW-kininogen was found in the liver of B/N-Ka rats (12). Thus, the cause of plasma deficiency of HMW-kininogen in the mutant appears to be secretory defect in nature. The B/N-Ka rats showed less reactivity to the inflammatory stimulus, such as carrageenin or kaolin, but the strain expressed almost the same response as normal rats to phorbol ester (PMA) or zymosan for pleurisy induction. These results indicate that kinin may play an important role in exudation in carrageenin- and kaolin-induced edema but not in that induced by PMA or zymosan. The deficient rat strain could be useful for differentiation of the inflammatory model which shows involvement of the kinin system.", "contents": "Kininogen deficiency in the rat. The Brown Norway Katholiek (B/N-Ka) strain rat is the only animal strain that demonstrates deficiency in plasma HMW- and LMW-kininogens with a low level of prekallikrein. We developed an RIA for rat HMW-kininogen, LMW-kininogen, and T-kininogen, and using them measured these proteins in B/N-Ka and normal strain (B/N-Ki) rats. Plasma level of immunoreactive as well as kinin-releasing HMW-kininogen and LMW-kininogen in B/N-Ka rats was either around 3% of their levels in the normal B/N-Ki rats. The cause of the plasma deficiency of kininogens in the B/N-Ka strain was examined by 35S-methionine uptake of primary cultures of hepatocytes from the B/N-Ki and B/N-Ka strains. The results indicated that the kininogens were synthesized in the B/N-Ka liver but not secreted into the medium. Northern blot analysis of poly A(+)RNA extracted from the livers of both strains demonstrated that the band corresponding to mRNA of HMW-kininogen was present in the mRNA from B/N-Ka liver as well as in that from the B/N-Ki one. The band was similar in size and intensity in both cases. This result confirmed the data that immunoreactive HMW-kininogen was found in the liver of B/N-Ka rats (12). Thus, the cause of plasma deficiency of HMW-kininogen in the mutant appears to be secretory defect in nature. The B/N-Ka rats showed less reactivity to the inflammatory stimulus, such as carrageenin or kaolin, but the strain expressed almost the same response as normal rats to phorbol ester (PMA) or zymosan for pleurisy induction. These results indicate that kinin may play an important role in exudation in carrageenin- and kaolin-induced edema but not in that induced by PMA or zymosan. The deficient rat strain could be useful for differentiation of the inflammatory model which shows involvement of the kinin system."} {"id": "PMID:1281610", "title": "T-kininogen, processing and functions.", "content": "Studies are presented which indicate that T-kininogen, the acute phase kininogen of the rat, could be a healing protein because of its properties as a cysteine protease inhibitor. Evidence is also presented that mRNA of T-kininogen synthesis may be a function of interleukin 6 production. A regulatory mechanism is postulated by which SH cofactors could determine if T-kinin is released or whether the T-kininogen molecule would remain intact. Evidence is also presented that T-kinin acts through kinin B2 receptors. No specific binding of bradykinin or T-kinin could be detected in rat heart preparations.", "contents": "T-kininogen, processing and functions. Studies are presented which indicate that T-kininogen, the acute phase kininogen of the rat, could be a healing protein because of its properties as a cysteine protease inhibitor. Evidence is also presented that mRNA of T-kininogen synthesis may be a function of interleukin 6 production. A regulatory mechanism is postulated by which SH cofactors could determine if T-kinin is released or whether the T-kininogen molecule would remain intact. Evidence is also presented that T-kinin acts through kinin B2 receptors. No specific binding of bradykinin or T-kinin could be detected in rat heart preparations."} {"id": "PMID:1281611", "title": "Further characterization of endopeptidase H2 a serine proteinase from human urine.", "content": "A human urine serine proteinase chymotrypsin like hydrolyzes the peptide bonds: Phe-Ser (kinin); Gly-Gly, Leu-Arg, Phe-Lys (neuropeptides) and Gln-Gln (substance P). Endopeptidase H2 hydrolyzes better oligopeptides with 4 to 18 aminoacid residues than larger peptides, it does not hydrolyzes kininogen or proenkephalin. The enzyme behaves as an oligoendopeptidase.", "contents": "Further characterization of endopeptidase H2 a serine proteinase from human urine. A human urine serine proteinase chymotrypsin like hydrolyzes the peptide bonds: Phe-Ser (kinin); Gly-Gly, Leu-Arg, Phe-Lys (neuropeptides) and Gln-Gln (substance P). Endopeptidase H2 hydrolyzes better oligopeptides with 4 to 18 aminoacid residues than larger peptides, it does not hydrolyzes kininogen or proenkephalin. The enzyme behaves as an oligoendopeptidase."} {"id": "PMID:1281612", "title": "Anti-idiotypic antibodies against the kinin receptor.", "content": "Three sets of monoclonal antibodies against bradykinin (MBK1, MBK2, MBK3) were generated by somatic cell fusion, characterized by their peptide specificity and compared to the known ligand specificity of the kinin receptor subtypes. By these criteria the paratope of MBK3 resembled the B2 receptor binding site whereas MBK1 shared principal binding characteristics with the B1 recrptor. Anti-idiotypic antibodies against MBK1, MBK2 and MBK3 were raised in rabbit and sheep. Specificity of the network components was verified by inhibition experiments on the level of peptide, idiotype and anti-idiotype. Anti-idiotypic antibodies against MBK3 recognized a conformation-dependent epitope which was binding site-related. Binding studies on human foreskin fibroblasts and guinea pig ileum showed mutual displacement of the anti-idiotypic antibody and bradykinin at the binding site pointing to a specific interaction of the antibody with the receptor from various species. An agonist activity of the antibodies, demonstrated in human (inositolphosphate pathway) and mouse (prostaglandin pathway) fibroblasts indicated that the anti-idiotypes bear an internal image of the ligand epitope. This molecular mimicry which was further substantiated by the detection of bradykinin specific anti-idiotypic antibodies, provides the structural basis for the observed cross-reactivity over species borders.", "contents": "Anti-idiotypic antibodies against the kinin receptor. Three sets of monoclonal antibodies against bradykinin (MBK1, MBK2, MBK3) were generated by somatic cell fusion, characterized by their peptide specificity and compared to the known ligand specificity of the kinin receptor subtypes. By these criteria the paratope of MBK3 resembled the B2 receptor binding site whereas MBK1 shared principal binding characteristics with the B1 recrptor. Anti-idiotypic antibodies against MBK1, MBK2 and MBK3 were raised in rabbit and sheep. Specificity of the network components was verified by inhibition experiments on the level of peptide, idiotype and anti-idiotype. Anti-idiotypic antibodies against MBK3 recognized a conformation-dependent epitope which was binding site-related. Binding studies on human foreskin fibroblasts and guinea pig ileum showed mutual displacement of the anti-idiotypic antibody and bradykinin at the binding site pointing to a specific interaction of the antibody with the receptor from various species. An agonist activity of the antibodies, demonstrated in human (inositolphosphate pathway) and mouse (prostaglandin pathway) fibroblasts indicated that the anti-idiotypes bear an internal image of the ligand epitope. This molecular mimicry which was further substantiated by the detection of bradykinin specific anti-idiotypic antibodies, provides the structural basis for the observed cross-reactivity over species borders."} {"id": "PMID:1281613", "title": "Identification of proteins of the kallikrein family by isoelectrofocusing and immunoblotting.", "content": "We have found that kallikrein-like proteins differ in their isoelectric point but share antigenic determinants. For identification of kallikrein-like proteins an initial separation was carried out in flat-bed isoelectrofocusing gels. The kallikrein-like nature was demonstrated by an immunological similarity to kallikrein-like proteins by immunoblotting using antiserum against a kallikrein family member for staining. We used this system to identify different kallikrein-like proteins during purification of both known as well as new enzymes.", "contents": "Identification of proteins of the kallikrein family by isoelectrofocusing and immunoblotting. We have found that kallikrein-like proteins differ in their isoelectric point but share antigenic determinants. For identification of kallikrein-like proteins an initial separation was carried out in flat-bed isoelectrofocusing gels. The kallikrein-like nature was demonstrated by an immunological similarity to kallikrein-like proteins by immunoblotting using antiserum against a kallikrein family member for staining. We used this system to identify different kallikrein-like proteins during purification of both known as well as new enzymes."} {"id": "PMID:1281614", "title": "Selective expression of sialyl-Lewis x and Lewis a epitopes, putative ligands for L-selectin, on peripheral lymph-node high endothelial venules.", "content": "High endothelial venules (HEV) lined by the high endothelium are the sites where leukocytes enter into the lymph nodes from the blood. Lymphocyte homing into lymph nodes is organ-selective, i.e., different molecules are involved in the lymphocyte homing to peripheral nodes compared with mucosa associated lymphoid tissue. The traffic into peripheral nodes is regulated by the expression of L-selectin on leukocytes and its ligand on HEVs. The ligand for L-selectin is suggested to be a 50, 90, or 105 kd glycoprotein, which is sulfated, fucosylated, and sialylated. The two other members of the selectin family (E- and P-selectin) recognize sialyl-Lewis x and -Lewis a (sLex and sLea, respectively) carbohydrate motifs, and there is preliminary data suggesting that this would also be the case for L-selectin. We have initiated a study to identify the expression of these sialylated structures on endothelial surfaces. We present data that show that HEVs in peripheral nodes, but not in the mucosa-associated lymphoid tissue, express large quantities of sLex and sLea identified by MAbs in immunohistology. Endothelium in capillaries or larger vessels in non-lymphoid tissues do not react with anti-sLex or -Lea mAbs. Only 1-2% of the lymphocytes in the peripheral blood express sLex and so far only the skin-homing lymphocytes are known to be sLex positive in larger quantities. We show that in many occasions the B cells in the peripheral lymph-node germinal centers are also sLex-, but not sLea-positive, and provide evidence of the restricted pattern of sLex and sLea expression on peripheral lymph-node HEVs. We propose that they are at least parts of the ligand for L-selectin.", "contents": "Selective expression of sialyl-Lewis x and Lewis a epitopes, putative ligands for L-selectin, on peripheral lymph-node high endothelial venules. High endothelial venules (HEV) lined by the high endothelium are the sites where leukocytes enter into the lymph nodes from the blood. Lymphocyte homing into lymph nodes is organ-selective, i.e., different molecules are involved in the lymphocyte homing to peripheral nodes compared with mucosa associated lymphoid tissue. The traffic into peripheral nodes is regulated by the expression of L-selectin on leukocytes and its ligand on HEVs. The ligand for L-selectin is suggested to be a 50, 90, or 105 kd glycoprotein, which is sulfated, fucosylated, and sialylated. The two other members of the selectin family (E- and P-selectin) recognize sialyl-Lewis x and -Lewis a (sLex and sLea, respectively) carbohydrate motifs, and there is preliminary data suggesting that this would also be the case for L-selectin. We have initiated a study to identify the expression of these sialylated structures on endothelial surfaces. We present data that show that HEVs in peripheral nodes, but not in the mucosa-associated lymphoid tissue, express large quantities of sLex and sLea identified by MAbs in immunohistology. Endothelium in capillaries or larger vessels in non-lymphoid tissues do not react with anti-sLex or -Lea mAbs. Only 1-2% of the lymphocytes in the peripheral blood express sLex and so far only the skin-homing lymphocytes are known to be sLex positive in larger quantities. We show that in many occasions the B cells in the peripheral lymph-node germinal centers are also sLex-, but not sLea-positive, and provide evidence of the restricted pattern of sLex and sLea expression on peripheral lymph-node HEVs. We propose that they are at least parts of the ligand for L-selectin."} {"id": "PMID:1281615", "title": "Interleukin-8. A corneal factor that induces neovascularization.", "content": "A rabbit corneal pocket model was used to demonstrate that physiologic concentrations of human recombinant (r) IL-8 may induce corneal neovascularization. Computer-assisted analysis of sequential fluorescein angiograms showed that rIL-8 doses ranging from 2 to 40 ng/cornea (P = 0.01), but not high dose rIL-8 (400 ng/cornea), results in neovascularization within 14 days. Repeat fluorescein angiograms 6 weeks after placing angiogenic doses of rIL-8 demonstrated significant regression (P = 0.01) of the vascularity present at 2 weeks, suggesting that IL-8 angiogenesis undergoes dynamic modulation similar to that normally seen in wound healing. To our knowledge, this is the first study showing an angiogenic role for IL-8, a finding that emphasizes the interplay between inflammation and wound healing. Our results imply that corneal-derived IL-8 may be important in corneal neovascularization, in particular, and that IL-8 may modulate wound healing in general. Finally, these results raise the possibility that corneal-derived cytokines, such as IL-8, may obfuscate the effects of agents tested in experimental corneal pocket models.", "contents": "Interleukin-8. A corneal factor that induces neovascularization. A rabbit corneal pocket model was used to demonstrate that physiologic concentrations of human recombinant (r) IL-8 may induce corneal neovascularization. Computer-assisted analysis of sequential fluorescein angiograms showed that rIL-8 doses ranging from 2 to 40 ng/cornea (P = 0.01), but not high dose rIL-8 (400 ng/cornea), results in neovascularization within 14 days. Repeat fluorescein angiograms 6 weeks after placing angiogenic doses of rIL-8 demonstrated significant regression (P = 0.01) of the vascularity present at 2 weeks, suggesting that IL-8 angiogenesis undergoes dynamic modulation similar to that normally seen in wound healing. To our knowledge, this is the first study showing an angiogenic role for IL-8, a finding that emphasizes the interplay between inflammation and wound healing. Our results imply that corneal-derived IL-8 may be important in corneal neovascularization, in particular, and that IL-8 may modulate wound healing in general. Finally, these results raise the possibility that corneal-derived cytokines, such as IL-8, may obfuscate the effects of agents tested in experimental corneal pocket models."} {"id": "PMID:1281616", "title": "Development and characterization of an experimental model of brain abscess in the rat.", "content": "Brain abscesses were produced in the rat by direct intracerebral injection of agarose beads laden with Staphylococcus aureus. The method proved to be easy, reproducible, effective and was associated with a low mortality rate. The histopathologic features of the experimental abscess are similar to other animal models and to human abscesses. The encapsulation of the lesion, macrophage/microglial response, astrocytic activation, and changes in the surrounding brain parenchyma were studied by immunohistochemistry. Edema, diffuse microglial activation and diffuse astrocytosis characterized the early reaction of the injected cerebral hemisphere. After day 10, edema subsided, and the microglial and astrocytic responses became restricted to the area around the lesion. Fibronectin deposition in the capsule preceded the appearance of myofibroblasts, which was concurrent with the beginning of collagen deposition on day 9. Hypervascularity of the capsule appeared as early as day 6 and persisted through day 28. This study suggests that brain abscess formation can be separated into three components: an initial period of edema and glial activation; an intermediate phase of neovascularization and fibronectin deposition; and a final phase of collagen deposition and progressive fibrosis. This new model offers an excellent paradigm for the analysis of neural tissue reaction and de novo fibrous tissue deposition.", "contents": "Development and characterization of an experimental model of brain abscess in the rat. Brain abscesses were produced in the rat by direct intracerebral injection of agarose beads laden with Staphylococcus aureus. The method proved to be easy, reproducible, effective and was associated with a low mortality rate. The histopathologic features of the experimental abscess are similar to other animal models and to human abscesses. The encapsulation of the lesion, macrophage/microglial response, astrocytic activation, and changes in the surrounding brain parenchyma were studied by immunohistochemistry. Edema, diffuse microglial activation and diffuse astrocytosis characterized the early reaction of the injected cerebral hemisphere. After day 10, edema subsided, and the microglial and astrocytic responses became restricted to the area around the lesion. Fibronectin deposition in the capsule preceded the appearance of myofibroblasts, which was concurrent with the beginning of collagen deposition on day 9. Hypervascularity of the capsule appeared as early as day 6 and persisted through day 28. This study suggests that brain abscess formation can be separated into three components: an initial period of edema and glial activation; an intermediate phase of neovascularization and fibronectin deposition; and a final phase of collagen deposition and progressive fibrosis. This new model offers an excellent paradigm for the analysis of neural tissue reaction and de novo fibrous tissue deposition."} {"id": "PMID:1281617", "title": "Regulated expression of vascular cell adhesion molecule-1 in human malignant melanoma.", "content": "Expression of the endothelial adhesion molecule VCAM-1 was studied in human malignant melanoma lines by flow cytometry. Clones 2/4 and 2/14 (derived from the same lesion) had appreciable levels of VCAM-1 expression, whereas clone 2/21 and the lines A2058, Mel24, and A375 were negative. Clone 2/14 was selected for further analysis. Exposure to tumor necrosis factor (TNF) markedly augmented VCAM-1 on melanoma cells. Surface VCAM-1 was associated with expression of specific transcripts that were augmented by TNF. Analysis by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that TNF-stimulated melanoma cells expressed both 7 and 6 immunoglobulin domain transcripts with predominance of the longer species. Tumor necrosis factor--stimulated melanoma cells bound more VLA-4-expressing cells (melanoma and monocytes) than resting tumor cells and anti-VCAM-1 monoclonal antibodies significantly inhibited binding, thus suggesting that surface VCAM-1 on melanoma is functional. Analysis of melanoma tissue sections demonstrated that VCAM-1 is not a marker of transformation of melanocytes because it can be detected in benign nevi. Although, unlike ICAM-1, VCAM-1 is not correlated with tumor progression, its expression in a fraction of primary melanomas indicates that it may play a role in regulating host immune response and homotypic interactions in some malignant melanomas.", "contents": "Regulated expression of vascular cell adhesion molecule-1 in human malignant melanoma. Expression of the endothelial adhesion molecule VCAM-1 was studied in human malignant melanoma lines by flow cytometry. Clones 2/4 and 2/14 (derived from the same lesion) had appreciable levels of VCAM-1 expression, whereas clone 2/21 and the lines A2058, Mel24, and A375 were negative. Clone 2/14 was selected for further analysis. Exposure to tumor necrosis factor (TNF) markedly augmented VCAM-1 on melanoma cells. Surface VCAM-1 was associated with expression of specific transcripts that were augmented by TNF. Analysis by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that TNF-stimulated melanoma cells expressed both 7 and 6 immunoglobulin domain transcripts with predominance of the longer species. Tumor necrosis factor--stimulated melanoma cells bound more VLA-4-expressing cells (melanoma and monocytes) than resting tumor cells and anti-VCAM-1 monoclonal antibodies significantly inhibited binding, thus suggesting that surface VCAM-1 on melanoma is functional. Analysis of melanoma tissue sections demonstrated that VCAM-1 is not a marker of transformation of melanocytes because it can be detected in benign nevi. Although, unlike ICAM-1, VCAM-1 is not correlated with tumor progression, its expression in a fraction of primary melanomas indicates that it may play a role in regulating host immune response and homotypic interactions in some malignant melanomas."} {"id": "PMID:1281618", "title": "Cutaneous expression of Thy-1 in mycosis fungoides.", "content": "Dermal dendritic cells from eleven cases of mycosis fungoides (MF) (six patch and five plaque stage), two cases of pre-MF, and five specimens of normal human skin, were characterized immunohistochemically using a panel of antibodies including anti-human Thy-1, intercellular adhesion molecule-1 (ICAM-1; CD54), endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD1a, CD2, CD14, CD18, CD34, MAC387, KP-1, EBM-11, factor XIIIa, factor XIIIs, and S100. Thy-1 expression in normal skin was limited to the microvascular endothelium and perivascular dendritic cells. An extensive interstitial network of Thy-1+ dendritic cells was seen in the papillary dermis of all cases of MF, whereas no epidermal cells were Thy-1+. The mean +/- standard deviation of interstitial Thy-1+ cells per high power field in the dermis was: normal skin, 2.86 +/- 0.34; pre-MF, 15; patch stage MF, 13.4 +/- 7.08; plaque stage MF, 49.96 +/- 21.29. Thy-1+ dendritic cells morphologically resembled the factor XIIIa+ \"dermal dendrocyte\" (DD) and shared their VCAM-1+, ICAM-1+, CD1a, CD2-, CD14+, CD18+, EMB11+, factor XIIIa+, factor XI-IIs-, S100-, MAC387- and KP-1-immunophenotype in MF. Double labeling studies revealed up to 50% of Thy-1+DD were also factor XIIIa+ in MF. Immediately beneath these cells was a similar network of CD34+, Thy-1-, factor XIIIa- dendritic cells limited to the reticular dermis. Strong microvascular endothelial cell expression of Thy-1 and VCAM-1, and focal vascular ELAM-1 expression were also seen in MF. Distinct cellular compartmentalization (papillary dermis versus reticular dermis versus epidermis) of dendritic cells is demonstrated by the differential expression of Thy-1, factor XIIIa, and CD34 antigens. The extensive number and prominent dermal dendritic network in the papillary dermis juxtaposed between epidermal keratinocytes (KC) and dermal/epidermal T cells, suggests an important pathophysiologic role for this newly recognized and immunophenotypically distinctive cell population in MF.", "contents": "Cutaneous expression of Thy-1 in mycosis fungoides. Dermal dendritic cells from eleven cases of mycosis fungoides (MF) (six patch and five plaque stage), two cases of pre-MF, and five specimens of normal human skin, were characterized immunohistochemically using a panel of antibodies including anti-human Thy-1, intercellular adhesion molecule-1 (ICAM-1; CD54), endothelial leukocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD1a, CD2, CD14, CD18, CD34, MAC387, KP-1, EBM-11, factor XIIIa, factor XIIIs, and S100. Thy-1 expression in normal skin was limited to the microvascular endothelium and perivascular dendritic cells. An extensive interstitial network of Thy-1+ dendritic cells was seen in the papillary dermis of all cases of MF, whereas no epidermal cells were Thy-1+. The mean +/- standard deviation of interstitial Thy-1+ cells per high power field in the dermis was: normal skin, 2.86 +/- 0.34; pre-MF, 15; patch stage MF, 13.4 +/- 7.08; plaque stage MF, 49.96 +/- 21.29. Thy-1+ dendritic cells morphologically resembled the factor XIIIa+ \"dermal dendrocyte\" (DD) and shared their VCAM-1+, ICAM-1+, CD1a, CD2-, CD14+, CD18+, EMB11+, factor XIIIa+, factor XI-IIs-, S100-, MAC387- and KP-1-immunophenotype in MF. Double labeling studies revealed up to 50% of Thy-1+DD were also factor XIIIa+ in MF. Immediately beneath these cells was a similar network of CD34+, Thy-1-, factor XIIIa- dendritic cells limited to the reticular dermis. Strong microvascular endothelial cell expression of Thy-1 and VCAM-1, and focal vascular ELAM-1 expression were also seen in MF. Distinct cellular compartmentalization (papillary dermis versus reticular dermis versus epidermis) of dendritic cells is demonstrated by the differential expression of Thy-1, factor XIIIa, and CD34 antigens. The extensive number and prominent dermal dendritic network in the papillary dermis juxtaposed between epidermal keratinocytes (KC) and dermal/epidermal T cells, suggests an important pathophysiologic role for this newly recognized and immunophenotypically distinctive cell population in MF."} {"id": "PMID:1281619", "title": "Renal extracellular matrix accumulation in acute puromycin aminonucleoside nephrosis in rats.", "content": "Progressive renal fibrosis is considered to be the final common pathway leading to chronic renal insufficiency. In this study, the authors examined some of the cellular and molecular mechanisms regulating the renal accumulation of extracellular matrix (ECM) proteins using rats with puromycin amino-nucleoside (PAN) nephrosis as an acute model system. Puromycin aminonucleoside rats developed reversible nephrotic syndrome accompanied by an interstitial infiltrate of monocytes. The number of interstitial fibroblasts expressing ST4 antigen did not increase. During the first 4 days, steady-state mRNA levels for all genes examined remained at or below control levels. At 1 week, nephrotic syndrome and interstitial inflammation were established, and a period of renal cell proliferation occurred, identified by increased histone mRNA levels and localized by tritiated thymine autoradiography to tubular epithelial cells and occasional interstitial cells. Transforming growth factor-beta (TGF-beta) steady-state mRNA levels were increased eightfold, but returned to control levels by 3 weeks. At week 1, there was a 10- to 20-fold increase in kidney steady-state mRNA levels for genes encoding interstitial matrix proteins collagen I and fibronectin and basement membrane collagen IV. By in situ hybridization, alpha 1(I) procollagen mRNA was localized to interstitial cells. Immunofluorescence microscopy demonstrated focal accumulation of ECM proteins in the tubulointerstitial compartment at 2 and 3 weeks, but by 6 weeks, kidney immunohistology was normal again. Steady-state mRNA levels for the matrix degrading metalloproteinase stromelysin remained at control values, whereas the levels for interstitial collagenase were normal at week 1 and increased twofold to threefold at 2 and 3 weeks. Steady-state mRNA levels for the tissue inhibitor of metalloproteinases (TIMP) increased fivefold at 1 week and returned to baseline values over the next 2 weeks. The results of this study suggest that tubulointerstitial ECM accumulation occurs in rats with acute PAN nephrosis because of the activation of genes encoding several matrix proteins and inhibition of matrix degradation mediated by TIMP. These events are reversed during the phase of recovery from nephrotic syndrome. Increased mRNA levels for TGF-beta, possibly originating from inflammatory interstitial monocytes, are likely to be one of the mediators of the molecular events observed.", "contents": "Renal extracellular matrix accumulation in acute puromycin aminonucleoside nephrosis in rats. Progressive renal fibrosis is considered to be the final common pathway leading to chronic renal insufficiency. In this study, the authors examined some of the cellular and molecular mechanisms regulating the renal accumulation of extracellular matrix (ECM) proteins using rats with puromycin amino-nucleoside (PAN) nephrosis as an acute model system. Puromycin aminonucleoside rats developed reversible nephrotic syndrome accompanied by an interstitial infiltrate of monocytes. The number of interstitial fibroblasts expressing ST4 antigen did not increase. During the first 4 days, steady-state mRNA levels for all genes examined remained at or below control levels. At 1 week, nephrotic syndrome and interstitial inflammation were established, and a period of renal cell proliferation occurred, identified by increased histone mRNA levels and localized by tritiated thymine autoradiography to tubular epithelial cells and occasional interstitial cells. Transforming growth factor-beta (TGF-beta) steady-state mRNA levels were increased eightfold, but returned to control levels by 3 weeks. At week 1, there was a 10- to 20-fold increase in kidney steady-state mRNA levels for genes encoding interstitial matrix proteins collagen I and fibronectin and basement membrane collagen IV. By in situ hybridization, alpha 1(I) procollagen mRNA was localized to interstitial cells. Immunofluorescence microscopy demonstrated focal accumulation of ECM proteins in the tubulointerstitial compartment at 2 and 3 weeks, but by 6 weeks, kidney immunohistology was normal again. Steady-state mRNA levels for the matrix degrading metalloproteinase stromelysin remained at control values, whereas the levels for interstitial collagenase were normal at week 1 and increased twofold to threefold at 2 and 3 weeks. Steady-state mRNA levels for the tissue inhibitor of metalloproteinases (TIMP) increased fivefold at 1 week and returned to baseline values over the next 2 weeks. The results of this study suggest that tubulointerstitial ECM accumulation occurs in rats with acute PAN nephrosis because of the activation of genes encoding several matrix proteins and inhibition of matrix degradation mediated by TIMP. These events are reversed during the phase of recovery from nephrotic syndrome. Increased mRNA levels for TGF-beta, possibly originating from inflammatory interstitial monocytes, are likely to be one of the mediators of the molecular events observed."} {"id": "PMID:1281620", "title": "Expression of sialyl-Lewis X, an E-selectin ligand, in inflammation, immune processes, and lymphoid tissues.", "content": "The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined.", "contents": "Expression of sialyl-Lewis X, an E-selectin ligand, in inflammation, immune processes, and lymphoid tissues. The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined."} {"id": "PMID:1281621", "title": "Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions.", "content": "Atherosclerotic lesions show features of a cell-mediated immune inflammatory process. From this viewpoint, the potential role of arterial endothelium in the recruitment of mononuclear cells (T lymphocytes and macrophages) was studied. The endothelium of diffuse intimal thickening (DIT) and atheromatous plaques (AP) in human coronary arteries and abdominal aortas was characterized for the expression of adhesion molecules ELAM-1, ICAM-1, and the major histocompatibility complex (MHC) class II antigens HLA-DR/DP. A marked increase in expression of ICAM-1 and ELAM-1, and to a lesser extent HLA-DR/DP was observed on endothelial cells that were adjacent to subendothelial infiltrates of T lymphocytes (CD3+, CD11a+, HLA-DR/DP+) and macrophages (CD14+, CD11a+, CD11c+, HLA-DR/DP+). This contrasted with a lower or absent expression of these activation markers at sites without prominent inflammatory cell infiltrates. These findings could be demonstrated in DIT as well as in AP. The observations suggest that cytokines produced by the subintimal infiltrates may activate the endothelium in a similar way as is observed in the microvasculature at sites of immune inflammation. The expression of these activation markers in the microvasculature is associated with enhanced leukocyte adhesion, permeability for macromolecules, and procoagulant activity, features known to occur also in early experimental atherosclerosis. The findings therefore support the concept that arterial endothelium plays an active role in the recruitment of mononuclear cells in atherosclerotic lesions.", "contents": "Adhesion molecules on the endothelium and mononuclear cells in human atherosclerotic lesions. Atherosclerotic lesions show features of a cell-mediated immune inflammatory process. From this viewpoint, the potential role of arterial endothelium in the recruitment of mononuclear cells (T lymphocytes and macrophages) was studied. The endothelium of diffuse intimal thickening (DIT) and atheromatous plaques (AP) in human coronary arteries and abdominal aortas was characterized for the expression of adhesion molecules ELAM-1, ICAM-1, and the major histocompatibility complex (MHC) class II antigens HLA-DR/DP. A marked increase in expression of ICAM-1 and ELAM-1, and to a lesser extent HLA-DR/DP was observed on endothelial cells that were adjacent to subendothelial infiltrates of T lymphocytes (CD3+, CD11a+, HLA-DR/DP+) and macrophages (CD14+, CD11a+, CD11c+, HLA-DR/DP+). This contrasted with a lower or absent expression of these activation markers at sites without prominent inflammatory cell infiltrates. These findings could be demonstrated in DIT as well as in AP. The observations suggest that cytokines produced by the subintimal infiltrates may activate the endothelium in a similar way as is observed in the microvasculature at sites of immune inflammation. The expression of these activation markers in the microvasculature is associated with enhanced leukocyte adhesion, permeability for macromolecules, and procoagulant activity, features known to occur also in early experimental atherosclerosis. The findings therefore support the concept that arterial endothelium plays an active role in the recruitment of mononuclear cells in atherosclerotic lesions."} {"id": "PMID:1281622", "title": "Estimation of tumor growth fractions in archival formalin-fixed, paraffin-embedded tissues using two anti-PCNA/Cyclin monoclonal antibodies. Factors affecting reactivity.", "content": "Immunohistochemical detection of cell cycle-related markers for estimation of tumor growth fractions using paraffin-embedded tissue sections would have applications in experimental and clinical pathology as an in situ histologic alternative to flow cytometry. The monoclonal antibodies 19A2 and PC10 detect the proliferating cell nuclear antigen (PCNA/Cyclin), an auxiliary protein to DNA polymerase-delta. In a prospective group of uniformly handled, formalin-fixed malignant lymphomas we previously demonstrated 19A2 to be a reliable marker of proliferative activity similar to Ki-67 in frozen tissue. The present study examines the applicability of this technique in archival formalin-fixed material. Studies on tonsilar tissue revealed that formalin fixation beyond 30 hours adversely affected reactivity of 19A2, possibly explaining the variable results in nonuniformly fixed archival material. We found that only 27 (56%) of 48 archival cases of infiltrating ductal carcinoma showed sufficient reactivity with 19A2 to permit reliable quantification of the tumor growth fraction. Acid pretreatment with 2N HCl had no apparent effect on 19A2 reactivity. Using both antibodies on a group of 32 archival lymphomas, carcinomas, and sarcomas, significantly more biopsies stained reliably for PC10 (84%) than for 19A2 (72%; P < 0.036). Further, none of the cases that did not react with PC10 reacted with 19A2. PC10 may recognize a different epitope of PCNA/Cyclin which may be more resistant to alterations by fixation. In the 23 cases that reliably stained for both markers, largely carcinomas, there was excellent correlation between estimated growth fractions (r = 0.96). Although immunostaining provides a useful way to estimate tumor growth fractions in paraffin-embedded tissues, modifications of technique and cautious interpretation of results are advisable when using archival material.", "contents": "Estimation of tumor growth fractions in archival formalin-fixed, paraffin-embedded tissues using two anti-PCNA/Cyclin monoclonal antibodies. Factors affecting reactivity. Immunohistochemical detection of cell cycle-related markers for estimation of tumor growth fractions using paraffin-embedded tissue sections would have applications in experimental and clinical pathology as an in situ histologic alternative to flow cytometry. The monoclonal antibodies 19A2 and PC10 detect the proliferating cell nuclear antigen (PCNA/Cyclin), an auxiliary protein to DNA polymerase-delta. In a prospective group of uniformly handled, formalin-fixed malignant lymphomas we previously demonstrated 19A2 to be a reliable marker of proliferative activity similar to Ki-67 in frozen tissue. The present study examines the applicability of this technique in archival formalin-fixed material. Studies on tonsilar tissue revealed that formalin fixation beyond 30 hours adversely affected reactivity of 19A2, possibly explaining the variable results in nonuniformly fixed archival material. We found that only 27 (56%) of 48 archival cases of infiltrating ductal carcinoma showed sufficient reactivity with 19A2 to permit reliable quantification of the tumor growth fraction. Acid pretreatment with 2N HCl had no apparent effect on 19A2 reactivity. Using both antibodies on a group of 32 archival lymphomas, carcinomas, and sarcomas, significantly more biopsies stained reliably for PC10 (84%) than for 19A2 (72%; P < 0.036). Further, none of the cases that did not react with PC10 reacted with 19A2. PC10 may recognize a different epitope of PCNA/Cyclin which may be more resistant to alterations by fixation. In the 23 cases that reliably stained for both markers, largely carcinomas, there was excellent correlation between estimated growth fractions (r = 0.96). Although immunostaining provides a useful way to estimate tumor growth fractions in paraffin-embedded tissues, modifications of technique and cautious interpretation of results are advisable when using archival material."} {"id": "PMID:1281623", "title": "Media conditioned by smooth muscle cells cultured in a variety of hypoxic environments stimulates in vitro angiogenesis. A relationship to transforming growth factor-beta 1.", "content": "Conditioned media (CM) harvested from bovine smooth muscle cells (SMCs) of aortic media cultured under hypoxic conditions remarkably enhanced angiogenesis in vitro, that is, the tube formation of bovine capillary endothelial cells (BCEs) cultured on type I collagen gels. The extent of in vitro angiogenesis was assessed by the total length of tube structures formed by BCEs per area measured quantitatively with an image analyzer. The tube formation in CM obtained from the cultivation of SMCs at 1% O2 for 24 hours was enhanced by about 1.5 times and 3.4 times as compared with those at 5% O2 and 20% O2, respectively. This tube-forming activity was abrogated by the pretreatment of CM with anti-transforming growth factor (TGF)-beta 1 IgG, but not by anti-basic fibroblast growth factor IgG. The SMC-CM obtained from hypoxic cultivation (1% O2 for 24 hours) inhibited [3H] thymidine incorporation by BCEs, SMCs, and fibroblasts more than about 20% of control. Anti-TGF-beta 1 IgG thus significantly reduced the inhibitory effect of hypoxic SMC-CM on DNA synthesis of these cells. These results suggest that SMCs in a hypoxic state release active in vitro angiogenic factors into CM, and active TGF-beta 1 is closely related to the in vitro angiogenic enhancement of media conditioned by SMCs cultured in a hypoxic state.", "contents": "Media conditioned by smooth muscle cells cultured in a variety of hypoxic environments stimulates in vitro angiogenesis. A relationship to transforming growth factor-beta 1. Conditioned media (CM) harvested from bovine smooth muscle cells (SMCs) of aortic media cultured under hypoxic conditions remarkably enhanced angiogenesis in vitro, that is, the tube formation of bovine capillary endothelial cells (BCEs) cultured on type I collagen gels. The extent of in vitro angiogenesis was assessed by the total length of tube structures formed by BCEs per area measured quantitatively with an image analyzer. The tube formation in CM obtained from the cultivation of SMCs at 1% O2 for 24 hours was enhanced by about 1.5 times and 3.4 times as compared with those at 5% O2 and 20% O2, respectively. This tube-forming activity was abrogated by the pretreatment of CM with anti-transforming growth factor (TGF)-beta 1 IgG, but not by anti-basic fibroblast growth factor IgG. The SMC-CM obtained from hypoxic cultivation (1% O2 for 24 hours) inhibited [3H] thymidine incorporation by BCEs, SMCs, and fibroblasts more than about 20% of control. Anti-TGF-beta 1 IgG thus significantly reduced the inhibitory effect of hypoxic SMC-CM on DNA synthesis of these cells. These results suggest that SMCs in a hypoxic state release active in vitro angiogenic factors into CM, and active TGF-beta 1 is closely related to the in vitro angiogenic enhancement of media conditioned by SMCs cultured in a hypoxic state."} {"id": "PMID:1281624", "title": "Monitoring of heparin-induced anticoagulation with kaolin-activated clotting time in cardiac surgical patients treated with aprotinin.", "content": "High-dose aprotinin appears to enhance the anticoagulant effects of heparin, as documented by increases in the activated clotting times (ACTs) during cardiopulmonary bypass; hence, some authorities have advocated reducing the dose of heparin in patients treated with aprotinin. An in vitro study by our group suggested that the increase of the ACT in the presence of aprotinin and heparin may be due to the use of celite as surface activator. We compared celite and kaolin as surface activators for the measurement of the ACT in cardiac surgical patients treated with aprotinin and in patients given no aprotinin. This double-blind, randomized, placebo-controlled study included 30 patients, of whom 14 received aprotinin and 16 received a placebo. Before, during, and after cardiopulmonary bypass, the ACT was measured with two Hemochron 400 systems with 12 mg of either celite (C-ACT) or kaolin (K-ACT) used as surface activator and with one Hepcon HMS system (HR-ACT), which uses kaolin as activator. The latter also was used for measurement of the blood heparin concentration. The ACTs of blood without heparin did not differ between aprotinin and control patients. During anticoagulation with heparin and cardiopulmonary bypass, the average C-ACTs were 784 +/- 301 s (aprotinin) and 496 +/- 120 s (control) (P < .001); the K-ACTs were 502 +/- 131 s (aprotinin) and 458 +/- 101 s (control) (P > .05); the HR-ACTs were 406 +/- 87 s (aprotinin) and 423 +/- 82 s (control) (P > .05), which was consistently less than C-ACT and K-ACT.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Monitoring of heparin-induced anticoagulation with kaolin-activated clotting time in cardiac surgical patients treated with aprotinin. High-dose aprotinin appears to enhance the anticoagulant effects of heparin, as documented by increases in the activated clotting times (ACTs) during cardiopulmonary bypass; hence, some authorities have advocated reducing the dose of heparin in patients treated with aprotinin. An in vitro study by our group suggested that the increase of the ACT in the presence of aprotinin and heparin may be due to the use of celite as surface activator. We compared celite and kaolin as surface activators for the measurement of the ACT in cardiac surgical patients treated with aprotinin and in patients given no aprotinin. This double-blind, randomized, placebo-controlled study included 30 patients, of whom 14 received aprotinin and 16 received a placebo. Before, during, and after cardiopulmonary bypass, the ACT was measured with two Hemochron 400 systems with 12 mg of either celite (C-ACT) or kaolin (K-ACT) used as surface activator and with one Hepcon HMS system (HR-ACT), which uses kaolin as activator. The latter also was used for measurement of the blood heparin concentration. The ACTs of blood without heparin did not differ between aprotinin and control patients. During anticoagulation with heparin and cardiopulmonary bypass, the average C-ACTs were 784 +/- 301 s (aprotinin) and 496 +/- 120 s (control) (P < .001); the K-ACTs were 502 +/- 131 s (aprotinin) and 458 +/- 101 s (control) (P > .05); the HR-ACTs were 406 +/- 87 s (aprotinin) and 423 +/- 82 s (control) (P > .05), which was consistently less than C-ACT and K-ACT.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281625", "title": "Morphine and hydromorphone epidural analgesia. A prospective, randomized comparison.", "content": "Because evidence from uncontrolled, unblinded studies suggested fewer side effects from epidural hydromorphone than from epidural morphine, we employed a randomized, blinded study design to compare the side effects of lumbar epidural morphine and hydromorphone in 55 adult, non-obstetric patients undergoing major surgical procedures. A bolus dose of epidural study drug was given at least 1 h prior to the conclusion of surgery, followed by a continuous infusion of the same drug for two postoperative days. Infusions were titrated to patient comfort. Visual analog scale (VAS) pain scores, VAS sedation scores, and subjective ratings of nausea and pruritus were assessed twice daily. The two treatments provided equivalent analgesia. Sedation scores and prevalence of nausea did not differ significantly between groups. Prevalence of pruritus, however, differed significantly on postoperative day 1, with moderate to severe pruritus reported by 44.4% of patients in the morphine group versus 11.5% in the hydromorphone group (P < .01). On post-operative day 2, reports of pruritus by patients receiving morphine remained higher than those among the hydromorphone-treated subjects, although this difference was no longer statistically significant (32% vs. 16.7%, P = .18). We conclude that lumbar epidural morphine and hydromorphone afford comparable analgesia, but the occurrence of moderate to severe pruritus on the first postoperative day is reduced by the use of hydromorphone.", "contents": "Morphine and hydromorphone epidural analgesia. A prospective, randomized comparison. Because evidence from uncontrolled, unblinded studies suggested fewer side effects from epidural hydromorphone than from epidural morphine, we employed a randomized, blinded study design to compare the side effects of lumbar epidural morphine and hydromorphone in 55 adult, non-obstetric patients undergoing major surgical procedures. A bolus dose of epidural study drug was given at least 1 h prior to the conclusion of surgery, followed by a continuous infusion of the same drug for two postoperative days. Infusions were titrated to patient comfort. Visual analog scale (VAS) pain scores, VAS sedation scores, and subjective ratings of nausea and pruritus were assessed twice daily. The two treatments provided equivalent analgesia. Sedation scores and prevalence of nausea did not differ significantly between groups. Prevalence of pruritus, however, differed significantly on postoperative day 1, with moderate to severe pruritus reported by 44.4% of patients in the morphine group versus 11.5% in the hydromorphone group (P < .01). On post-operative day 2, reports of pruritus by patients receiving morphine remained higher than those among the hydromorphone-treated subjects, although this difference was no longer statistically significant (32% vs. 16.7%, P = .18). We conclude that lumbar epidural morphine and hydromorphone afford comparable analgesia, but the occurrence of moderate to severe pruritus on the first postoperative day is reduced by the use of hydromorphone."} {"id": "PMID:1281628", "title": "Effect of ageing on responses of nerve fibres to pulpal inflammation in rat molars analysed by quantitative immunocytochemistry.", "content": "The response of sensory nerve fibres to inflammation in young adult rat molars has recently been shown to include increases in nerve sprouting and neuropeptide content. The objective was to evaluate neural responses to class V dental preparations in molars of old (1-2 yr) as compared with young adult rats (3-4 months). Tissues were investigated immunocytochemically 4 days post-injury for the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P. Quantitative image analysis of the material demonstrated that more immunoreactivity was present for CGRP than for substance P in intact control teeth for each age group. Four days after injury, both immunoreactivities were increased in pulp adjacent to the injury in both young and old teeth. The increase depended on at least three factors: (1) enhanced immunoreactivity of the nerve fibres; (2) increased terminal nerve sprouts near the injury and (3) elevated peptide content of the pulp tissue. Although the incidence of CGRP- and substance P-immunoreactive nerve fibres had decreased in older teeth, the proportional increases in both neuropeptides near the injury were greater in old than in young teeth, owing to a reduction in pulpal volume during ageing. Pulpal tissue was also immunostained for the low-affinity nerve growth factor receptor (p75-NGFR) as an index of pulpal ageing; and an extensive decrease was found in the old adult as compared to young adult rats. These results indicate that old rats maintain the capacity for nerve sprouting despite the decreases in p75-NGFR labelling of pulp cells, pulp volume and nerve fibre numbers that occur as part of dental ageing.", "contents": "Effect of ageing on responses of nerve fibres to pulpal inflammation in rat molars analysed by quantitative immunocytochemistry. The response of sensory nerve fibres to inflammation in young adult rat molars has recently been shown to include increases in nerve sprouting and neuropeptide content. The objective was to evaluate neural responses to class V dental preparations in molars of old (1-2 yr) as compared with young adult rats (3-4 months). Tissues were investigated immunocytochemically 4 days post-injury for the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P. Quantitative image analysis of the material demonstrated that more immunoreactivity was present for CGRP than for substance P in intact control teeth for each age group. Four days after injury, both immunoreactivities were increased in pulp adjacent to the injury in both young and old teeth. The increase depended on at least three factors: (1) enhanced immunoreactivity of the nerve fibres; (2) increased terminal nerve sprouts near the injury and (3) elevated peptide content of the pulp tissue. Although the incidence of CGRP- and substance P-immunoreactive nerve fibres had decreased in older teeth, the proportional increases in both neuropeptides near the injury were greater in old than in young teeth, owing to a reduction in pulpal volume during ageing. Pulpal tissue was also immunostained for the low-affinity nerve growth factor receptor (p75-NGFR) as an index of pulpal ageing; and an extensive decrease was found in the old adult as compared to young adult rats. These results indicate that old rats maintain the capacity for nerve sprouting despite the decreases in p75-NGFR labelling of pulp cells, pulp volume and nerve fibre numbers that occur as part of dental ageing."} {"id": "PMID:1281629", "title": "Collagen gene expression in human dental pulp cell cultures.", "content": "Pulp cells from human permanent molars were isolated and established in culture; 40% showed positive alkaline phosphatase staining. When incubated with 50 micrograms/ml of ascorbic acid and 10 mM of beta-glycerophosphate, the cells formed a mineralized extracellular matrix; they could thus have the potential to differentiate into odontoblast-like cells in vitro. Collagen synthesis was analysed by SDS interrupted gel electrophoresis, Northern blot and slot blot: the cells produced predominantly (approximately 99%) type I collagen and only trace amount of type III collagen. The ratio of alpha 1 (I) to alpha 2(I) procollagen chains was about 68:32, indicating that no significant amount of collagen type I trimer was synthesized in this system. The ratios of alpha 1(I), alpha 2(I) and alpha 1(III) procollagen mRNAs were about 61:25:1; these were compatible with the ratios of corresponding procollagen alpha chains. In addition, a novel 5.8 kb pro alpha 1(III) mRNA was detected. These observations indicate that collagen synthesis in these cultured pulp cells was regulated at the transcriptional level.", "contents": "Collagen gene expression in human dental pulp cell cultures. Pulp cells from human permanent molars were isolated and established in culture; 40% showed positive alkaline phosphatase staining. When incubated with 50 micrograms/ml of ascorbic acid and 10 mM of beta-glycerophosphate, the cells formed a mineralized extracellular matrix; they could thus have the potential to differentiate into odontoblast-like cells in vitro. Collagen synthesis was analysed by SDS interrupted gel electrophoresis, Northern blot and slot blot: the cells produced predominantly (approximately 99%) type I collagen and only trace amount of type III collagen. The ratio of alpha 1 (I) to alpha 2(I) procollagen chains was about 68:32, indicating that no significant amount of collagen type I trimer was synthesized in this system. The ratios of alpha 1(I), alpha 2(I) and alpha 1(III) procollagen mRNAs were about 61:25:1; these were compatible with the ratios of corresponding procollagen alpha chains. In addition, a novel 5.8 kb pro alpha 1(III) mRNA was detected. These observations indicate that collagen synthesis in these cultured pulp cells was regulated at the transcriptional level."} {"id": "PMID:1281630", "title": "CD59 (homologous restriction factor 20), a plasma membrane protein that protects against complement C5b-9 attack, in human atherosclerotic lesions.", "content": "Blood cells express a cell membrane protein, termed homologous restriction factor 20 (HRF20) and identical to CD59, that can inhibit complement C5b-9 insertion into their membranes. In this report, we investigated by immunohistochemistry whether CD59 was present on cells in human atherosclerotic lesions since membranous C5b-9(m) has been found in lesions. Using a monoclonal anti-CD59 antibody, a cellular CD59 staining pattern was apparent in nearly all lesion specimens. CD59 stain co-localised with macrophage (CD14), T lymphocyte (CD7), endothelial cell (anti-factor VIII related antigen) and smooth muscle cell cytoskeletal-specific antigens (anti-alpha actin and muscle myosin). Endothelial cells always exhibited a more intense stain than the other cell types. CD59 antigen was not localised to any one area of the lesions. Usually CD59-positive cells occurred in clusters rather than as randomly spaced individual cells. CD59 did not stain all cells of the lesion and in particular did not appear to stain all smooth muscle cells. Areas of CD59-negative cells were sometimes observed to exhibit a cellular C5b-9 staining pattern. C5b-9 deposits were also observed in CD59-positive regions. Normal saphenous vein stained strongly for CD59 at the endothelial lining and weakly in the media. Capillaries in atherosclerotic intima always stained strongly for CD59. We conclude that HRF20 is constitutively expressed on endothelium and is under regulatory control in smooth muscle cells. Cellular C5b-9 attack in atherosclerotic lesions is therefore most likely to occur on smooth muscle cells.", "contents": "CD59 (homologous restriction factor 20), a plasma membrane protein that protects against complement C5b-9 attack, in human atherosclerotic lesions. Blood cells express a cell membrane protein, termed homologous restriction factor 20 (HRF20) and identical to CD59, that can inhibit complement C5b-9 insertion into their membranes. In this report, we investigated by immunohistochemistry whether CD59 was present on cells in human atherosclerotic lesions since membranous C5b-9(m) has been found in lesions. Using a monoclonal anti-CD59 antibody, a cellular CD59 staining pattern was apparent in nearly all lesion specimens. CD59 stain co-localised with macrophage (CD14), T lymphocyte (CD7), endothelial cell (anti-factor VIII related antigen) and smooth muscle cell cytoskeletal-specific antigens (anti-alpha actin and muscle myosin). Endothelial cells always exhibited a more intense stain than the other cell types. CD59 antigen was not localised to any one area of the lesions. Usually CD59-positive cells occurred in clusters rather than as randomly spaced individual cells. CD59 did not stain all cells of the lesion and in particular did not appear to stain all smooth muscle cells. Areas of CD59-negative cells were sometimes observed to exhibit a cellular C5b-9 staining pattern. C5b-9 deposits were also observed in CD59-positive regions. Normal saphenous vein stained strongly for CD59 at the endothelial lining and weakly in the media. Capillaries in atherosclerotic intima always stained strongly for CD59. We conclude that HRF20 is constitutively expressed on endothelium and is under regulatory control in smooth muscle cells. Cellular C5b-9 attack in atherosclerotic lesions is therefore most likely to occur on smooth muscle cells."} {"id": "PMID:1281631", "title": "Substrate-bound fibrinogen, fibrin and other cell attachment-promoting proteins as a scaffold for cultured vascular smooth muscle cells.", "content": "We have previously reported that fibrinogen/fibrin can induce the migration of vascular smooth muscle cells in vitro. In this study, we examined the effect of substrate-bound fibrinogen/fibrin and other cell attachment-promoting proteins on the adhesion of vascular smooth muscle cells. The amount of fibrinogen/fibrin adsorbed to plastic wells and the adhesion of smooth muscle cells to the wells were found to depend on the concentration of fibrinogen used for coating the wells. The effect of fibrinogen/fibrin was comparable to that of so-called cell attachment-promoting proteins (fibronectin, vitronectin, and type I collagen). Adhesion of smooth muscle cells to fibrinogen/fibrin-coated wells was inhibited by the synthetic peptide GRGDS, but not by a control peptide, GRGES. Vitronectin, fibronectin, type I collagen, denatured type I collagen and commercial gelatin also induced smooth muscle cell adhesion. The adhesion induced by vitronectin, denatured type I collagen, and commercial gelatin was inhibited by GRGDS. However, the adhesion induced by type I collagen was not influenced and that induced by fibronectin was only slightly inhibited. These observations suggest that fibrinogen/fibrin deposited extracellularly in the arterial intima may act as a scaffold in the process of smooth muscle cell migration.", "contents": "Substrate-bound fibrinogen, fibrin and other cell attachment-promoting proteins as a scaffold for cultured vascular smooth muscle cells. We have previously reported that fibrinogen/fibrin can induce the migration of vascular smooth muscle cells in vitro. In this study, we examined the effect of substrate-bound fibrinogen/fibrin and other cell attachment-promoting proteins on the adhesion of vascular smooth muscle cells. The amount of fibrinogen/fibrin adsorbed to plastic wells and the adhesion of smooth muscle cells to the wells were found to depend on the concentration of fibrinogen used for coating the wells. The effect of fibrinogen/fibrin was comparable to that of so-called cell attachment-promoting proteins (fibronectin, vitronectin, and type I collagen). Adhesion of smooth muscle cells to fibrinogen/fibrin-coated wells was inhibited by the synthetic peptide GRGDS, but not by a control peptide, GRGES. Vitronectin, fibronectin, type I collagen, denatured type I collagen and commercial gelatin also induced smooth muscle cell adhesion. The adhesion induced by vitronectin, denatured type I collagen, and commercial gelatin was inhibited by GRGDS. However, the adhesion induced by type I collagen was not influenced and that induced by fibronectin was only slightly inhibited. These observations suggest that fibrinogen/fibrin deposited extracellularly in the arterial intima may act as a scaffold in the process of smooth muscle cell migration."} {"id": "PMID:1281632", "title": "Group A streptococcal M proteins: virulence factors and protective antigens.", "content": "Rebecca Lancefield described group A streptococcal M proteins over 50 years ago, and they have remained at the forefront of investigations into streptococcal pathogenicity to the present day. As described in this review, they form cell surface fibrils with several functions, ranging from resisting phagocytosis and inducing host-crossreactive antibodies, to presenting the host immune system with an accessible protective antigen.", "contents": "Group A streptococcal M proteins: virulence factors and protective antigens. Rebecca Lancefield described group A streptococcal M proteins over 50 years ago, and they have remained at the forefront of investigations into streptococcal pathogenicity to the present day. As described in this review, they form cell surface fibrils with several functions, ranging from resisting phagocytosis and inducing host-crossreactive antibodies, to presenting the host immune system with an accessible protective antigen."} {"id": "PMID:1281633", "title": "Molecular mapping of human band 3 aging antigenic sites and active amino acids using synthetic peptides.", "content": "An aging antigen, senescent cell antigen appears on old cells and marks them for death by initiating the binding of IgG autoantibody and subsequent removal by phagocytes. This antigen is derived from the major anion transport protein, protein band 3, that is involved in respiration and acid base balance. We use synthetic peptides from the transmembrane, anion transport segment of band 3 to \"walk\" band 3 to identify potential aging antigenic sites. A competitive inhibition assay with affinity purified IgG autoantibody from senescent red cells was used. Results indicate that: aging antigenic sites reside on human band 3 residues 538-554, 593-601, and 812-830; and that the smallest residues which act as aging antigenic sites are 593-601 and 813-818. The contribution of lysine and/or arginine to antigenicity is examined by synthesizing peptide analogs in which glycines or arginines are substituted for lysines or arginines. Substitution of neutral glycine for the positively charged amino acids arginine or lysine or both arginine and lysine did not result in a significant difference in antigenicity between the analog and the native band 3 peptide. Substitution of the positively charged arginine for the positively charged lysine resulted in a significant reduction in antigenicity. The chicken sequence of band 3 peptides 538-554 and 812-827 differs from that of the human peptides at several sites. Antigenicity of these chicken \"analogs\" were tested and compared to the human peptides. The data suggest that the three-dimensional configuration of band 3 segments plays a dominant role in defining the antigenic determinants reactive with senescent cell IgG autoantibodies.", "contents": "Molecular mapping of human band 3 aging antigenic sites and active amino acids using synthetic peptides. An aging antigen, senescent cell antigen appears on old cells and marks them for death by initiating the binding of IgG autoantibody and subsequent removal by phagocytes. This antigen is derived from the major anion transport protein, protein band 3, that is involved in respiration and acid base balance. We use synthetic peptides from the transmembrane, anion transport segment of band 3 to \"walk\" band 3 to identify potential aging antigenic sites. A competitive inhibition assay with affinity purified IgG autoantibody from senescent red cells was used. Results indicate that: aging antigenic sites reside on human band 3 residues 538-554, 593-601, and 812-830; and that the smallest residues which act as aging antigenic sites are 593-601 and 813-818. The contribution of lysine and/or arginine to antigenicity is examined by synthesizing peptide analogs in which glycines or arginines are substituted for lysines or arginines. Substitution of neutral glycine for the positively charged amino acids arginine or lysine or both arginine and lysine did not result in a significant difference in antigenicity between the analog and the native band 3 peptide. Substitution of the positively charged arginine for the positively charged lysine resulted in a significant reduction in antigenicity. The chicken sequence of band 3 peptides 538-554 and 812-827 differs from that of the human peptides at several sites. Antigenicity of these chicken \"analogs\" were tested and compared to the human peptides. The data suggest that the three-dimensional configuration of band 3 segments plays a dominant role in defining the antigenic determinants reactive with senescent cell IgG autoantibodies."} {"id": "PMID:1281634", "title": "Method for calculating 3-D coordinates from molecular stereograms.", "content": "The three-dimensional coordinates for the alpha-carbon atoms of crambin and basic pancreatic trypsin inhibitor (BPTI) were determined from the respective alpha-carbon trace stereograms using an improved Simplex algorithm. This algorithm was used in a two-step process to estimate the z-coordinate values. In one approach, an average interatomic distance value, an approximate viewing angle, and a table of digitized values for xleft, yleft and xright, yright are provided in the first step. In the second step, the z-coordinate values are derived by varying z to minimize the bond distance error (Rossmann and Argos, 1980). In another approach, only a reference bond distance table is provided along with the table of xleft, yleft and xright, yright digitized values. In the first step, the viewing angle (phi), a combined scale and viewing distance parameter (q), a rotational angular distortion from digitizing and/or photocopying (z), and translational distortion factors (xerr and yerr) are calculated. In the second step, the z-coordinate values are varied to minimize the bond distance error. RMS difference values of less than 1.5 A were obtained for both crambin and BPTI alpha-carbon atoms.", "contents": "Method for calculating 3-D coordinates from molecular stereograms. The three-dimensional coordinates for the alpha-carbon atoms of crambin and basic pancreatic trypsin inhibitor (BPTI) were determined from the respective alpha-carbon trace stereograms using an improved Simplex algorithm. This algorithm was used in a two-step process to estimate the z-coordinate values. In one approach, an average interatomic distance value, an approximate viewing angle, and a table of digitized values for xleft, yleft and xright, yright are provided in the first step. In the second step, the z-coordinate values are derived by varying z to minimize the bond distance error (Rossmann and Argos, 1980). In another approach, only a reference bond distance table is provided along with the table of xleft, yleft and xright, yright digitized values. In the first step, the viewing angle (phi), a combined scale and viewing distance parameter (q), a rotational angular distortion from digitizing and/or photocopying (z), and translational distortion factors (xerr and yerr) are calculated. In the second step, the z-coordinate values are varied to minimize the bond distance error. RMS difference values of less than 1.5 A were obtained for both crambin and BPTI alpha-carbon atoms."} {"id": "PMID:1281635", "title": "Identification and characterization of an anti-isoaspartic acid monoclonal antibody.", "content": "The deamidation and rearrangement of protein-bound asparagine residues occurs when peptides and proteins are exposed to acidic or alkaline aqueous media. Asn99 of bovine growth hormone (bGH) is readily modified via these mechanisms. We have generated a monoclonal antibody (MAb) that interacts with a bGH fragment that contains an isoaspartyl residue. To obtain this antibody, CAF1/J mice were immunized with [isoaspartyl99]-bGH(96-112) conjugated to BSA. Using a competitive ELISA assay, the interaction of this MAb to [isoaspartyl99]-bGH(96-112) has been observed to have an apparent Km of 150 nM. The corresponding native peptide and other bGH fragments do not bind to this antibody with high affinity. For example, the binding affinities of [Asp99]-bGH(96-112) and [Glu99]-bGH(96-112) to this antibody are 54- and 78-fold lower than the corresponding isoaspartyl peptide. The antibody also binds to bGH that is enriched in isoaspartic acid at position 99, but not to the unmodified protein. The binding epitope of the peptide has been further characterized by comparing the binding of bGH(96-112) analogues to the MAb. Alanine substitution at residues 99, 100, 101, and 103 reduce binding affinity to the antibody by more than 10(3)-fold. Replacement of valine with alanine at position 102 has much less impact on antibody affinity. Further experiments suggest that the relative insensitivity to this substitution is due to the structural similarity of these sidechains. Other isoaspartic acid-containing peptides not derived from the bGH sequence do not bind to the antibody. We conclude that the epitope binding site of this MAb is highly specific for 99-103 of [isoaspartyl99]-bGH (96-112).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Identification and characterization of an anti-isoaspartic acid monoclonal antibody. The deamidation and rearrangement of protein-bound asparagine residues occurs when peptides and proteins are exposed to acidic or alkaline aqueous media. Asn99 of bovine growth hormone (bGH) is readily modified via these mechanisms. We have generated a monoclonal antibody (MAb) that interacts with a bGH fragment that contains an isoaspartyl residue. To obtain this antibody, CAF1/J mice were immunized with [isoaspartyl99]-bGH(96-112) conjugated to BSA. Using a competitive ELISA assay, the interaction of this MAb to [isoaspartyl99]-bGH(96-112) has been observed to have an apparent Km of 150 nM. The corresponding native peptide and other bGH fragments do not bind to this antibody with high affinity. For example, the binding affinities of [Asp99]-bGH(96-112) and [Glu99]-bGH(96-112) to this antibody are 54- and 78-fold lower than the corresponding isoaspartyl peptide. The antibody also binds to bGH that is enriched in isoaspartic acid at position 99, but not to the unmodified protein. The binding epitope of the peptide has been further characterized by comparing the binding of bGH(96-112) analogues to the MAb. Alanine substitution at residues 99, 100, 101, and 103 reduce binding affinity to the antibody by more than 10(3)-fold. Replacement of valine with alanine at position 102 has much less impact on antibody affinity. Further experiments suggest that the relative insensitivity to this substitution is due to the structural similarity of these sidechains. Other isoaspartic acid-containing peptides not derived from the bGH sequence do not bind to the antibody. We conclude that the epitope binding site of this MAb is highly specific for 99-103 of [isoaspartyl99]-bGH (96-112).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281636", "title": "Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 113-120 (antigenic site 4) of myoglobin.", "content": "Immunochemical cross-reactivity of protein variants has been very frequently used to map protein antigenic sites. The approach is based on the assumption that amino acid substitutions affecting the binding of a protein to its antibody, particularly when monoclonal antibodies (mAbs) are used, must be part of the antigenic site and not far from it. The assumption was investigated in this study by determining the effects of amino acid substitutions outside the antigenic site on the reactivity of six myoglobin (Mb) variants with three mAbs of predetermined specificity prepared by immunization with a free synthetic peptide representing region 113-120 (antigenic site 4) of Mb. Two of the Mb variants used had no substitutions within residues 113-120 (the region to which the specificity of the mAbs is directed) and yet exhibited markedly decreased cross-reactions and binding affinities, relative to the reference antigen, sperm-whale Mb. The other three Mb variants possessed substitutions within, as well as outside, region 113-120 and showed very little cross-reactivities. The results of this study, particularly with the Mbs that have no substitutions within the indicated antigenic site, clearly show that substitutions outside the site, and which by design are not part of the site, can influence very markedly the reactivity of the protein variant with the anti-site mAbs. The approach can, therefore, lead to serious errors if used to identify residues of protein antigenic sites.", "contents": "Effects of amino acid substitutions outside an antigenic site on protein binding to monoclonal antibodies of predetermined specificity obtained by peptide immunization: demonstration with region 113-120 (antigenic site 4) of myoglobin. Immunochemical cross-reactivity of protein variants has been very frequently used to map protein antigenic sites. The approach is based on the assumption that amino acid substitutions affecting the binding of a protein to its antibody, particularly when monoclonal antibodies (mAbs) are used, must be part of the antigenic site and not far from it. The assumption was investigated in this study by determining the effects of amino acid substitutions outside the antigenic site on the reactivity of six myoglobin (Mb) variants with three mAbs of predetermined specificity prepared by immunization with a free synthetic peptide representing region 113-120 (antigenic site 4) of Mb. Two of the Mb variants used had no substitutions within residues 113-120 (the region to which the specificity of the mAbs is directed) and yet exhibited markedly decreased cross-reactions and binding affinities, relative to the reference antigen, sperm-whale Mb. The other three Mb variants possessed substitutions within, as well as outside, region 113-120 and showed very little cross-reactivities. The results of this study, particularly with the Mbs that have no substitutions within the indicated antigenic site, clearly show that substitutions outside the site, and which by design are not part of the site, can influence very markedly the reactivity of the protein variant with the anti-site mAbs. The approach can, therefore, lead to serious errors if used to identify residues of protein antigenic sites."} {"id": "PMID:1281637", "title": "Studies on human porin. VIII. Expression of \"Porin 31HL\" channels in the plasmalemma of the acute-lymphoblastic-leukemia cell line KM3 as revealed by light- and electron-microscopy.", "content": "First electron microscopy data on the expression of the VDAC \"Porin 31HL\" in the plasmalemma of a eucaryotic cell are presented. In a light and electron microscopic study we demonstrate the expression of the porin channel in the outer cell membrane of the pre-B lymphocyte type acute-lymphoblastic-leukemia cell line KM3. Monoclonal mouse anti-\"Porin 31HL\" antibodies were applied in indirect immunofluorescence or immunogold labelling experiments. The results confirm our early topological data on the expression of porin channels in the cytoplasmic membrane of different human cell types as revealed on the light microscopy level. Interestingly, only a pre-embedding immunoreaction approach was successful for gold particle labelling of the plasmalemma. This again is in agreement with our recent data on the accessibility of the acetylated N-terminal part of \"Porin 31HL\" molecules on the outer cell surface.", "contents": "Studies on human porin. VIII. Expression of \"Porin 31HL\" channels in the plasmalemma of the acute-lymphoblastic-leukemia cell line KM3 as revealed by light- and electron-microscopy. First electron microscopy data on the expression of the VDAC \"Porin 31HL\" in the plasmalemma of a eucaryotic cell are presented. In a light and electron microscopic study we demonstrate the expression of the porin channel in the outer cell membrane of the pre-B lymphocyte type acute-lymphoblastic-leukemia cell line KM3. Monoclonal mouse anti-\"Porin 31HL\" antibodies were applied in indirect immunofluorescence or immunogold labelling experiments. The results confirm our early topological data on the expression of porin channels in the cytoplasmic membrane of different human cell types as revealed on the light microscopy level. Interestingly, only a pre-embedding immunoreaction approach was successful for gold particle labelling of the plasmalemma. This again is in agreement with our recent data on the accessibility of the acetylated N-terminal part of \"Porin 31HL\" molecules on the outer cell surface."} {"id": "PMID:1281638", "title": "B-cell tolerance.", "content": "Discrimination between self and non-self in humoral immunity is mediated in part by elimination or inactivation of self-reactive B-cell clones. This type of repertoire censoring requires that self-reactive B cells make a choice between these and alternative cellular fates. The details of this developmental decision-making and the steps where it is prone to go awry in autoimmunity have yet to be untangled, but genetic analysis appears likely to lead the way.", "contents": "B-cell tolerance. Discrimination between self and non-self in humoral immunity is mediated in part by elimination or inactivation of self-reactive B-cell clones. This type of repertoire censoring requires that self-reactive B cells make a choice between these and alternative cellular fates. The details of this developmental decision-making and the steps where it is prone to go awry in autoimmunity have yet to be untangled, but genetic analysis appears likely to lead the way."} {"id": "PMID:1281639", "title": "Non-MHC-linked genes in autoimmune diseases.", "content": "The gene responsible for the lpr mutation in MRL mice that are prone to systemic lupus erythematosus has been shown to encode the apoptosis-inducing Fas antigen, thus pointing to control of apoptosis as a major regulatory mechanism in autoimmunity. In the non-obese diabetic mouse model for insulin-dependent diabetes, four non-MHC-linked loci have been localized in the murine genome that were found to be associated with successive stages of the disease. These findings should soon have a major impact on our understanding of human autoimmune diseases.", "contents": "Non-MHC-linked genes in autoimmune diseases. The gene responsible for the lpr mutation in MRL mice that are prone to systemic lupus erythematosus has been shown to encode the apoptosis-inducing Fas antigen, thus pointing to control of apoptosis as a major regulatory mechanism in autoimmunity. In the non-obese diabetic mouse model for insulin-dependent diabetes, four non-MHC-linked loci have been localized in the murine genome that were found to be associated with successive stages of the disease. These findings should soon have a major impact on our understanding of human autoimmune diseases."} {"id": "PMID:1281640", "title": "Genetic and immunological mechanisms in the pathogenesis of systemic lupus erythematosus.", "content": "Recent research in systemic lupus erythematosus and animal models of lupus has provided new insight into the pathogenesis of this complex autoimmune disease. Progress has been made towards understanding the genetic contributions to disease susceptibility and induction, as well as towards elucidation of the lymphocyte abnormalities involved in pathogenic autoantibody production.", "contents": "Genetic and immunological mechanisms in the pathogenesis of systemic lupus erythematosus. Recent research in systemic lupus erythematosus and animal models of lupus has provided new insight into the pathogenesis of this complex autoimmune disease. Progress has been made towards understanding the genetic contributions to disease susceptibility and induction, as well as towards elucidation of the lymphocyte abnormalities involved in pathogenic autoantibody production."} {"id": "PMID:1281641", "title": "Multiple sclerosis: an autoimmune disease of multifactorial etiology.", "content": "The etiology of multiple sclerosis is linked to a variety of genetic and environmental factors. Both cell-mediated and humoral immune responses, triggered by extraneous or autoantigens, are likely to contribute to the pathogenesis of this disease. A greater insight into the fundamental cause of multiple sclerosis has been provided by the recognition that certain immune response genes are associated with an increased susceptibility to the disease. Such knowledge should provide new opportunities for selective therapeutic interventions.", "contents": "Multiple sclerosis: an autoimmune disease of multifactorial etiology. The etiology of multiple sclerosis is linked to a variety of genetic and environmental factors. Both cell-mediated and humoral immune responses, triggered by extraneous or autoantigens, are likely to contribute to the pathogenesis of this disease. A greater insight into the fundamental cause of multiple sclerosis has been provided by the recognition that certain immune response genes are associated with an increased susceptibility to the disease. Such knowledge should provide new opportunities for selective therapeutic interventions."} {"id": "PMID:1281642", "title": "Direct in vitro infection of human intestine with HIV-1.", "content": "To directly infect human fetal intestine with HIV in vitro. Human fetal intestinal explant cultures were exposed to HIV-1 and monitored for evidence of infection by biochemical assay, immunohistochemistry and in situ hybridization. Human fetal intestinal explants (14-21 weeks) were established in culture and exposed to HIV-1. Tissue culture fluid was assayed for p24 antigen and reverse transcriptase activity over a 14-day period. Explants were removed from culture on days 4, 7, 10 and 14 postinoculation and subjected (1) to immunohistochemistry to detect p24 and gp160/41 antigens, and (2) to in situ hybridization to detect HIV-1 RNA. Explant tissue culture fluid was cocultured with Jurkat T-cells to detect infectious viral particles. Reverse transcriptase activity and p24 antigen levels in fetal explant culture fluid rose between 7 and 14 days after viral inoculation. Jurkat T-cell cocultures confirmed the presence of infectious virus. Cells in the lamina propria resembling lymphocytes and macrophages of both small intestine and colon stained positively for the viral proteins p24 and gp41. The same type of cells also stained positively for HIV-1 RNA using in situ hybridization. Dual-label immunohistochemistry, combined immunohistochemistry and in situ hybridization confirmed the presence of viral protein and RNA in cells bearing the CD3, CD4 (lymphocyte) or CD68 (macrophage) surface markers. There was no evidence at any time of HIV-1 infection of epithelial cells. Cells of the lamina propria of the small intestine and colon, bearing lymphocyte or macrophage markers, can be directly infected by and support the replication of HIV-1. Such infection may be implicated in the pathogenesis of HIV enteropathy.", "contents": "Direct in vitro infection of human intestine with HIV-1. To directly infect human fetal intestine with HIV in vitro. Human fetal intestinal explant cultures were exposed to HIV-1 and monitored for evidence of infection by biochemical assay, immunohistochemistry and in situ hybridization. Human fetal intestinal explants (14-21 weeks) were established in culture and exposed to HIV-1. Tissue culture fluid was assayed for p24 antigen and reverse transcriptase activity over a 14-day period. Explants were removed from culture on days 4, 7, 10 and 14 postinoculation and subjected (1) to immunohistochemistry to detect p24 and gp160/41 antigens, and (2) to in situ hybridization to detect HIV-1 RNA. Explant tissue culture fluid was cocultured with Jurkat T-cells to detect infectious viral particles. Reverse transcriptase activity and p24 antigen levels in fetal explant culture fluid rose between 7 and 14 days after viral inoculation. Jurkat T-cell cocultures confirmed the presence of infectious virus. Cells in the lamina propria resembling lymphocytes and macrophages of both small intestine and colon stained positively for the viral proteins p24 and gp41. The same type of cells also stained positively for HIV-1 RNA using in situ hybridization. Dual-label immunohistochemistry, combined immunohistochemistry and in situ hybridization confirmed the presence of viral protein and RNA in cells bearing the CD3, CD4 (lymphocyte) or CD68 (macrophage) surface markers. There was no evidence at any time of HIV-1 infection of epithelial cells. Cells of the lamina propria of the small intestine and colon, bearing lymphocyte or macrophage markers, can be directly infected by and support the replication of HIV-1. Such infection may be implicated in the pathogenesis of HIV enteropathy."} {"id": "PMID:1281643", "title": "Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin.", "content": "To evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma. A retrospective case notes review. The departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK. All patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. Treatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5-5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. Response, toxicity and survival. Overall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 10(6) (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9. months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. Treatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens.", "contents": "Kaposi's sarcoma in HIV infection treated with vincristine and bleomycin. To evaluate the efficacy and toxicity of vincristine and bleomycin when used in combination to treat patients with progressive Kaposi's sarcoma. A retrospective case notes review. The departments of Immunology and Genito-Urinary Medicine, St Mary's Hospital, London, UK. All patients presenting with progressive Kaposi's sarcoma and requiring chemotherapy between January 1987 and January 1990, who had received no previous systemic chemotherapy. Treatment with vincristine (2 mg) and bleomycin (30 mg, 18 h infusion), or vinblastine (2.5-5.0 mg) if peripheral neuropathy developed. Treatment with zidovudine and prophylaxis of opportunistic infections where indicated. Response, toxicity and survival. Overall, patients had a poor prognosis: 33 out of 46 (72%) had had a previous opportunistic infection, had a mean CD4 count of 144 x 10(6) (20 out of 46 tested) and a mean Karnofsky index of 75.4. They received a median of five cycles of therapy: a partial response was achieved in twenty-six patients (57%), disease progression was halted in a further 16 (35%), while disease progression continued in four (9%) despite therapy; there were no complete responders. Mean duration of response was 2 months (s.d., 1.26 months), survival was 8 months (s.d., 6.7 months) from start of therapy and 17 months (s.d., 8.9. months) from first AIDS diagnosis. On multivariate analysis the best predictor of mortality was the presence of previous opportunistic infection (P = 0.00653). Side-effects were minimal in comparison with other studies. The most common side-effect, in 13 cases (28%), was peripheral neuropathy, which may in part represent the prevalence of HIV neuropathy or remain as background. Haematological toxicity was uncommon. Treatment for HIV-related Kaposi's sarcoma in advanced HIV disease is becoming more necessary as disease profiles change. Conventional chemotherapy regimens for malignancy are not well tolerated in these patients and may not be indicated. This regimen is effective and has low toxicity in AIDS patients. Non-responders should be considered for more intensive regimens."} {"id": "PMID:1281645", "title": "Possible regulatory role of dynorphin A in the urinary bladder.", "content": "Muscle strips from rat and human detrusor were studied using indirect immunofluorescence and electrical nerve stimulation in an organ bath. Immunoreactivity towards dynorphin was observed in varicose nerve fibres in the detrusor muscle and around immunonegative nerve cell bodies in the prevesical ganglia of the rat. In vitro, dynorphin A (1-13) (10(-13)-10(-6) M) strongly facilitated detrusor contraction induced by electrical field stimulation (EFS). This facilitation was counteracted by morphine (10(-10) and 10(-8) M) and naloxone (10(-10) and 10(-8) M) in a competitive manner. The facilitation could also be counteracted by the addition of the kappa-receptor antagonist M(r) 2266 (10(-7) M). Muscarinic blockade, achieved with atropine (10(-6) M), did not alter the effect of dynorphin A (1-13). Addition of phentolamine mesylate (10(-6) M), and propranolol (10(-6) M) per se facilitated the EFS-induced contractions. Both adrenergic blockade as well as the addition of the substance P blocker spantide, counteracted the facilitating effect of dynorphin A (1-13). Dynorphin A immunoreactive material was found to be present in nerves in the rat detrusor and in prevesical ganglia. Dynorphin A (1-13) facilitated the detrusor contraction, possibly via actions on kappa-opioid receptors and interaction with non-cholinergic nerves.", "contents": "Possible regulatory role of dynorphin A in the urinary bladder. Muscle strips from rat and human detrusor were studied using indirect immunofluorescence and electrical nerve stimulation in an organ bath. Immunoreactivity towards dynorphin was observed in varicose nerve fibres in the detrusor muscle and around immunonegative nerve cell bodies in the prevesical ganglia of the rat. In vitro, dynorphin A (1-13) (10(-13)-10(-6) M) strongly facilitated detrusor contraction induced by electrical field stimulation (EFS). This facilitation was counteracted by morphine (10(-10) and 10(-8) M) and naloxone (10(-10) and 10(-8) M) in a competitive manner. The facilitation could also be counteracted by the addition of the kappa-receptor antagonist M(r) 2266 (10(-7) M). Muscarinic blockade, achieved with atropine (10(-6) M), did not alter the effect of dynorphin A (1-13). Addition of phentolamine mesylate (10(-6) M), and propranolol (10(-6) M) per se facilitated the EFS-induced contractions. Both adrenergic blockade as well as the addition of the substance P blocker spantide, counteracted the facilitating effect of dynorphin A (1-13). Dynorphin A immunoreactive material was found to be present in nerves in the rat detrusor and in prevesical ganglia. Dynorphin A (1-13) facilitated the detrusor contraction, possibly via actions on kappa-opioid receptors and interaction with non-cholinergic nerves."} {"id": "PMID:1281646", "title": "Increased CSF HVA response to arecoline challenge in Alzheimer's disease.", "content": "The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p < .01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease.", "contents": "Increased CSF HVA response to arecoline challenge in Alzheimer's disease. The effects of the muscarinic agonist, arecoline, on the concentration of homovanillic acid (HVA) in the cerebrospinal fluid of patients with Alzheimer's disease (AD) and controls were examined. Patients and controls received intravenous infusions of arecoline and a lumbar puncture was performed four hours after the infusion began. Arecoline induced a significant increase in the concentration of HVA in cerebrospinal fluid of Alzheimer's disease patients (p < .01) but not in controls. The differential HVA response to a muscarinic agonist in Alzheimer's disease is suggestive of an alteration in muscarinic receptor response. This finding may have potential implications for the pathophysiology and treatment of Alzheimer's disease."} {"id": "PMID:1281647", "title": "Rescuing transgene expression by co-integration.", "content": "To test whether foreign gene expression can be improved in transgenic mice by manipulating the site of integration, we co-integrated the efficiently expressed sheep beta-lactoglobulin gene with two poorly expressed beta-lactoglobulin-derived hybrid genes encoding human proteins. In each case, we observed a significant improvement in the frequency and level of expression of the hybrid gene. \"Rescuing\" transgene expression by co-integration may provide a general solution for improving the efficiency of heterologous gene expression in transgenic animals.", "contents": "Rescuing transgene expression by co-integration. To test whether foreign gene expression can be improved in transgenic mice by manipulating the site of integration, we co-integrated the efficiently expressed sheep beta-lactoglobulin gene with two poorly expressed beta-lactoglobulin-derived hybrid genes encoding human proteins. In each case, we observed a significant improvement in the frequency and level of expression of the hybrid gene. \"Rescuing\" transgene expression by co-integration may provide a general solution for improving the efficiency of heterologous gene expression in transgenic animals."} {"id": "PMID:1281648", "title": "Determination of estrogen receptors in paraffin-embedded tissue. Techniques and the value in breast cancer treatment.", "content": "Estrogen receptor (ER) analysis in breast cancer has been used in three clinical situations: to select patients with advanced breast cancer for hormonal therapy, as a prognostic parameter, and for selection of women with early breast cancer to adjuvant hormonal treatment. ER has traditionally been measured using labelled hormone in binding assays--often in dextran-coated charcoal assays (DCC). Monoclonal antibodies to ER has permitted development of a solid phase enzyme immunoassay (ER-EIA) used for quantitative determination of ER in tissue homogenates, and have also been used for determination of ER using an immunohistochemical assay in frozen sections (ER-ICA) or in formalin-fixed, paraffin-embedded tissue (ER-PAR). A large number of studies has compared ER-EIA with ER-DCC assays. There is a good linear correlation between the two types of assay but ER-EIA measure more ER and classify a larger fraction of tumors ER-positive than conventional ER assays. Lack of clinical data makes the significance of this uncertain. Numerous studies have reported on the correlation between ER-ICA and ER-DCC or ER-EIA. There is a good correlation among the assays on classification of ER status with a median 86% concordance, but a somewhat poorer correlation between semiquantified ER of immunohistochemical assays and ER determined by the quantitative methods (median coefficient of correlation 0.67). There is a large variation in the cut-off level for definition of ER-positive in immunohistochemical assays emphasizing the need for quality control studies. The major problem involved in ER analysis in paraffin-embedded tissue is a considerable loss of immunoreactivity compared to sections from frozen tissue. This can partly be overcome by modifications of the immunohistochemical technique using enzyme pretreatment and other amplification systems, but the sensitivity of ER-PAR remains lower than ER-ICA despite these modifications, and the ER status is less reliably determined in tumors with low ER contents (< 100 fmol). The prognostic value of ER-PAR was evaluated with a multivariate analysis. The endpoint was disease-free interval in systemically untreated patients with early breast cancer, and the variables used were: ER-DCC, ER-PAR, age, tumor size, tumor grade, and nodal status. A total of 133 patients from the Danish Breast Cancer Cooperative Group's (DBCG) 77c protocols had a complete set of variables. The analysis showed that only nodal status, ER-DCC, and tumor grade were significant and independent prognostic variables. An overview of larger multivariate studies on mainly node-negative patients failed to show independent prognostic significance of ER-DCC.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Determination of estrogen receptors in paraffin-embedded tissue. Techniques and the value in breast cancer treatment. Estrogen receptor (ER) analysis in breast cancer has been used in three clinical situations: to select patients with advanced breast cancer for hormonal therapy, as a prognostic parameter, and for selection of women with early breast cancer to adjuvant hormonal treatment. ER has traditionally been measured using labelled hormone in binding assays--often in dextran-coated charcoal assays (DCC). Monoclonal antibodies to ER has permitted development of a solid phase enzyme immunoassay (ER-EIA) used for quantitative determination of ER in tissue homogenates, and have also been used for determination of ER using an immunohistochemical assay in frozen sections (ER-ICA) or in formalin-fixed, paraffin-embedded tissue (ER-PAR). A large number of studies has compared ER-EIA with ER-DCC assays. There is a good linear correlation between the two types of assay but ER-EIA measure more ER and classify a larger fraction of tumors ER-positive than conventional ER assays. Lack of clinical data makes the significance of this uncertain. Numerous studies have reported on the correlation between ER-ICA and ER-DCC or ER-EIA. There is a good correlation among the assays on classification of ER status with a median 86% concordance, but a somewhat poorer correlation between semiquantified ER of immunohistochemical assays and ER determined by the quantitative methods (median coefficient of correlation 0.67). There is a large variation in the cut-off level for definition of ER-positive in immunohistochemical assays emphasizing the need for quality control studies. The major problem involved in ER analysis in paraffin-embedded tissue is a considerable loss of immunoreactivity compared to sections from frozen tissue. This can partly be overcome by modifications of the immunohistochemical technique using enzyme pretreatment and other amplification systems, but the sensitivity of ER-PAR remains lower than ER-ICA despite these modifications, and the ER status is less reliably determined in tumors with low ER contents (< 100 fmol). The prognostic value of ER-PAR was evaluated with a multivariate analysis. The endpoint was disease-free interval in systemically untreated patients with early breast cancer, and the variables used were: ER-DCC, ER-PAR, age, tumor size, tumor grade, and nodal status. A total of 133 patients from the Danish Breast Cancer Cooperative Group's (DBCG) 77c protocols had a complete set of variables. The analysis showed that only nodal status, ER-DCC, and tumor grade were significant and independent prognostic variables. An overview of larger multivariate studies on mainly node-negative patients failed to show independent prognostic significance of ER-DCC.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281649", "title": "Variations in the content of steroid receptors in breast cancer. Comparison between primary tumors and metastatic lesions.", "content": "Steroid receptors were determined by the dextran-coated charcoal method in 193 breast cancer patients in different clinical stages of disease. Quantitative estrogen and progesterone values in primary tumors (n = 69) were compared with receptors in regional lymph node metastases (n = 28) and in distant malignant deposits (n = 65). The groups including receptor values from primaries and regional lymph node metastases (n = 15) and from primaries and distant metastatic lesions (n = 16) in the same patients were also analyzed. The obtained results indicated relative stability of both receptors in loco-regional disease, but with a tendency towards lower receptor values in lesions from advanced disease. This tendency is probably caused by the disease progression itself, but the influence of radio- or chemotherapy cannot be excluded.", "contents": "Variations in the content of steroid receptors in breast cancer. Comparison between primary tumors and metastatic lesions. Steroid receptors were determined by the dextran-coated charcoal method in 193 breast cancer patients in different clinical stages of disease. Quantitative estrogen and progesterone values in primary tumors (n = 69) were compared with receptors in regional lymph node metastases (n = 28) and in distant malignant deposits (n = 65). The groups including receptor values from primaries and regional lymph node metastases (n = 15) and from primaries and distant metastatic lesions (n = 16) in the same patients were also analyzed. The obtained results indicated relative stability of both receptors in loco-regional disease, but with a tendency towards lower receptor values in lesions from advanced disease. This tendency is probably caused by the disease progression itself, but the influence of radio- or chemotherapy cannot be excluded."} {"id": "PMID:1281650", "title": "General condition of asymptomatic patients with advanced colorectal cancer receiving palliative chemotherapy. A longitudinal study.", "content": "A Nordic multicenter study in asymptomatic patients with advanced colorectal cancer compared initial chemotherapy with sequential methotrexate-5-FU with leucovorin rescue (MFL) for 6 months versus primary expectancy with chemotherapy only after the appearance of symptoms. The study (183 patients randomized between January 1985 and February 1990) showed that symptom-free survival, progression-free survival and survival respectively were about 6 months longer in the group of patients randomized to initial MFL. Whether these prolongations could be achieved without an impaired 'quality of life' was studied in an associated study. Between January 1985 and March 1987, 43 patients were randomized at one of the hospitals, 36 of which were interviewed with a questionnaire at randomization. Even if all these patients were considered, by the physician, to be 'free of symptoms from their disease', 16/36 (44%) had symptoms that could be referred to the disease. In spite of this, the patients were in a good general condition, and considerably better off than patients considered to have 'symptoms from the disease' who were interviewed with the same questionnaire when randomized in a parallel study of symptomatic patients. Patients randomized to initial chemotherapy and interviewed longitudinally maintained their good condition throughout treatment. Toxicity was mild, although the patients expressed more adverse effects than the physicians recorded. Since symptom-free survival, progression-free survival and survival were statistically significantly longer in the group of patients randomized to MFL also in this associated study, it is concluded that initial chemotherapy can prolong symptom-free survival and survival without reduced 'quality of life' during the treatment period.", "contents": "General condition of asymptomatic patients with advanced colorectal cancer receiving palliative chemotherapy. A longitudinal study. A Nordic multicenter study in asymptomatic patients with advanced colorectal cancer compared initial chemotherapy with sequential methotrexate-5-FU with leucovorin rescue (MFL) for 6 months versus primary expectancy with chemotherapy only after the appearance of symptoms. The study (183 patients randomized between January 1985 and February 1990) showed that symptom-free survival, progression-free survival and survival respectively were about 6 months longer in the group of patients randomized to initial MFL. Whether these prolongations could be achieved without an impaired 'quality of life' was studied in an associated study. Between January 1985 and March 1987, 43 patients were randomized at one of the hospitals, 36 of which were interviewed with a questionnaire at randomization. Even if all these patients were considered, by the physician, to be 'free of symptoms from their disease', 16/36 (44%) had symptoms that could be referred to the disease. In spite of this, the patients were in a good general condition, and considerably better off than patients considered to have 'symptoms from the disease' who were interviewed with the same questionnaire when randomized in a parallel study of symptomatic patients. Patients randomized to initial chemotherapy and interviewed longitudinally maintained their good condition throughout treatment. Toxicity was mild, although the patients expressed more adverse effects than the physicians recorded. Since symptom-free survival, progression-free survival and survival were statistically significantly longer in the group of patients randomized to MFL also in this associated study, it is concluded that initial chemotherapy can prolong symptom-free survival and survival without reduced 'quality of life' during the treatment period."} {"id": "PMID:1281651", "title": "MACOP-B regimen in non-Hodgkin's lymphoma.", "content": "Two university centers in Finland used MACOP-B regimen as first-line treatment of intermediate and high-grade non-Hodgkin's lymphomas in 1986-1990. The clinical records of all 41 patients treated with this regimen were analyzed. The median age was 47 years (range 16-65), 24% of the patients had WHO performance status > 1, 49% had B-symptoms, 46% had Ann Arbor stage III or IV disease, and 39% had bulky disease. Twenty-three (58%) of the 40 patients who were evaluable for response had CR. The survival rate 36 months after the start of MACOP-B was 62%, but failure-free survival rate only 36%. Among several analyzed factors a lactate dehydrogenase level < 500 U/l before treatment showed the strongest association to failure-free survival. The planned dose intensity was not achieved mainly because of toxicity, and the ratio of the actual dose intensity given to the planned dose intensity varied for the different drugs between 0.77 and 0.92.", "contents": "MACOP-B regimen in non-Hodgkin's lymphoma. Two university centers in Finland used MACOP-B regimen as first-line treatment of intermediate and high-grade non-Hodgkin's lymphomas in 1986-1990. The clinical records of all 41 patients treated with this regimen were analyzed. The median age was 47 years (range 16-65), 24% of the patients had WHO performance status > 1, 49% had B-symptoms, 46% had Ann Arbor stage III or IV disease, and 39% had bulky disease. Twenty-three (58%) of the 40 patients who were evaluable for response had CR. The survival rate 36 months after the start of MACOP-B was 62%, but failure-free survival rate only 36%. Among several analyzed factors a lactate dehydrogenase level < 500 U/l before treatment showed the strongest association to failure-free survival. The planned dose intensity was not achieved mainly because of toxicity, and the ratio of the actual dose intensity given to the planned dose intensity varied for the different drugs between 0.77 and 0.92."} {"id": "PMID:1281652", "title": "Macrophage-neoplastic cell interactions: implications for neoplastic cell growth.", "content": "Subcutaneous transplantation of EL4 lymphoma cells within C57BL10 mice evoked an oedematous inflammatory response involving increased leukopoiesis within the bone marrow, a blood leukocytosis, an influx of leukocytes into the transplants and surrounding host connective tissues, and extensive remodelling of surrounding host connective tissues involving fibroplasia and angiogenesis. Dexamethasone not only significantly reduced the numbers of circulating blood leukocytes within C57BL10 mice bearing the subcutaneous EL4 lymphoma transplants, but also reduced the oedematous inflammatory response to the transplants. The decreased influx of inflammatory leukocytes into the site of EL4 lymphoma cell transplantation within the dexamethasone-treated mice, was accompanied by reduced growth of the transplants. Although the EL4 lymphoma cells produce factors with Colony Stimulating Factor activity and with chemotactic activity for cells of the monocyte-macrophage lineage, they do not appear to produce fibroblast growth factors directly but can induce (or stimulate) macrophages to generate fibroblast growth factors in vitro. While not directly inhibiting the growth of subcutaneous fibroblasts in vitro, dexamethasone does suppress the production and/or activity of fibroblast growth factors generated through macrophage-EL4 cell interactions in vitro. The inhibitory effects of dexamethasone on macrophage influx, fibroplasia and angiogenesis within the connective tissue surrounding the EL4 lymphoma transplants appear to be casually related events and would account for the inhibitory effect of dexamethasone on the growth of the lymphoma transplants.", "contents": "Macrophage-neoplastic cell interactions: implications for neoplastic cell growth. Subcutaneous transplantation of EL4 lymphoma cells within C57BL10 mice evoked an oedematous inflammatory response involving increased leukopoiesis within the bone marrow, a blood leukocytosis, an influx of leukocytes into the transplants and surrounding host connective tissues, and extensive remodelling of surrounding host connective tissues involving fibroplasia and angiogenesis. Dexamethasone not only significantly reduced the numbers of circulating blood leukocytes within C57BL10 mice bearing the subcutaneous EL4 lymphoma transplants, but also reduced the oedematous inflammatory response to the transplants. The decreased influx of inflammatory leukocytes into the site of EL4 lymphoma cell transplantation within the dexamethasone-treated mice, was accompanied by reduced growth of the transplants. Although the EL4 lymphoma cells produce factors with Colony Stimulating Factor activity and with chemotactic activity for cells of the monocyte-macrophage lineage, they do not appear to produce fibroblast growth factors directly but can induce (or stimulate) macrophages to generate fibroblast growth factors in vitro. While not directly inhibiting the growth of subcutaneous fibroblasts in vitro, dexamethasone does suppress the production and/or activity of fibroblast growth factors generated through macrophage-EL4 cell interactions in vitro. The inhibitory effects of dexamethasone on macrophage influx, fibroplasia and angiogenesis within the connective tissue surrounding the EL4 lymphoma transplants appear to be casually related events and would account for the inhibitory effect of dexamethasone on the growth of the lymphoma transplants."} {"id": "PMID:1281653", "title": "[Molecular cloning and expression of Vibrio cholerae LPS O-antigen genes in E. coli HB101].", "content": "The chromosomal fragments of Vibrio Cholerae Classic Biotype and Eltor Biotype were cloned respectively with vector plasmid pUC18 and B.S(M13+). We got recombinants which could express the LPS O-Antigen of Vibrio cholerae, and the expressed O-Antigen expressed had very good specificity and immunogenicity. After analyzing the recombinant plasmids by restriction endonucleases digestion, we found the size of foreign fragments in pMG-301 and pMG-302 were 8.4 kb and 7.6 kb, which were much smaller than 16 kb fragment reported by documents and great difference existed between the gene's structure.", "contents": "[Molecular cloning and expression of Vibrio cholerae LPS O-antigen genes in E. coli HB101]. The chromosomal fragments of Vibrio Cholerae Classic Biotype and Eltor Biotype were cloned respectively with vector plasmid pUC18 and B.S(M13+). We got recombinants which could express the LPS O-Antigen of Vibrio cholerae, and the expressed O-Antigen expressed had very good specificity and immunogenicity. After analyzing the recombinant plasmids by restriction endonucleases digestion, we found the size of foreign fragments in pMG-301 and pMG-302 were 8.4 kb and 7.6 kb, which were much smaller than 16 kb fragment reported by documents and great difference existed between the gene's structure."} {"id": "PMID:1281655", "title": "Decline in CTL and antibody responses to HIV-1 p17 and p24 antigens in HIV-1-infected hemophiliacs irrespective of disease progression. A 5-year follow-up study.", "content": "CTL and antibody responses to HIV-1 p17 and p24 antigens were monitored from 1986-1991, in 4 hemophiliacs. The patients had been infected with HIV-1 between 1980 and 1984. Two patients have remained asymptomatic while two progressed to AIDS in 1990. CTL were boosted by culturing with peptides from p17 aa 86-115, or p24 aa 265-279; and aa 270-373 or PHA. Lysis was measured on autologous or allogeneic targets pulsed with peptides or infected with recombinant vaccinia virus carrying HIV-1 gag or influenza A matrix genes. Antibodies to p17 and p24 were tested by ELISA using peptides and by Western blotting. High levels of CTL activity to p17 and p24 antigens could be generated only with lymphocytes from the two asymptomatic patients between 1986 and 1989, but these responses were absent in 1990 and 1991. Antibodies to p17 peptides disappeared in parallel with CTL activity. Antibodies to some p24 peptides also declined but most patients retained activity to others. In all patients a > or = 3-fold increase in CD8+ cell numbers occurred over time and accompanied the decline of CTL and antibody responses. The loss of CTL and p17 antibodies occurred irrespective of whether patients remained asymptomatic or progressed to AIDS in the intervening two years.", "contents": "Decline in CTL and antibody responses to HIV-1 p17 and p24 antigens in HIV-1-infected hemophiliacs irrespective of disease progression. A 5-year follow-up study. CTL and antibody responses to HIV-1 p17 and p24 antigens were monitored from 1986-1991, in 4 hemophiliacs. The patients had been infected with HIV-1 between 1980 and 1984. Two patients have remained asymptomatic while two progressed to AIDS in 1990. CTL were boosted by culturing with peptides from p17 aa 86-115, or p24 aa 265-279; and aa 270-373 or PHA. Lysis was measured on autologous or allogeneic targets pulsed with peptides or infected with recombinant vaccinia virus carrying HIV-1 gag or influenza A matrix genes. Antibodies to p17 and p24 were tested by ELISA using peptides and by Western blotting. High levels of CTL activity to p17 and p24 antigens could be generated only with lymphocytes from the two asymptomatic patients between 1986 and 1989, but these responses were absent in 1990 and 1991. Antibodies to p17 peptides disappeared in parallel with CTL activity. Antibodies to some p24 peptides also declined but most patients retained activity to others. In all patients a > or = 3-fold increase in CD8+ cell numbers occurred over time and accompanied the decline of CTL and antibody responses. The loss of CTL and p17 antibodies occurred irrespective of whether patients remained asymptomatic or progressed to AIDS in the intervening two years."} {"id": "PMID:1281661", "title": "Reappraisal of the coupling interval of ventricular extrasystoles as an index of ectopic mechanisms.", "content": "A mathematical model of modulated ventricular parasystole based on the relation between the coupling interval and the preceding RR interval was developed in an attempt to distinguish between parasystolic automaticity and other mechanisms. MATHEMATICAL MODEL: The relation between the coupling interval and the preceding RR interval was examined by plotting the coupling interval of each extrasystole against the preceding RR interval (coupling interval/RR diagram). The coupling interval/RR diagrams obtained from simulations with various modulation modes suggested that the parasystolic mechanism was likely when the dots representing extrasystoles appeared as discrete clusters. In contrast, a linear horizontal accumulation of dots indicated a non-parasystolic mechanism. To verify the validity of the simulations, 24 hour electrocardiographic recordings from 60 patients with frequent ventricular extrasystoles (> 1000/day) were analysed to determine whether the extrasystoles showed intrinsic periodicity. Intrinsic periodicity indicative of a parasystolic mechanism was seen in 14 (93%) of 15 patients in whom the coupling interval/RR diagram was characteristic of a parasystolic mechanism. When the coupling interval did not change (variability < 200 ms) over a wide range of RR intervals (> 700 ms) intrinsic periodicity was never identified (0/17). Parasystolic automaticity was the likely mechanism in 11 of the remaining 28 patients (39.3%) in whom coupling interval/RR diagrams were not definitive. These data indicate that definite patterns of coupling interval/RR diagrams can be used to distinguish between parasystolic and non-parasystolic mechanisms.", "contents": "Reappraisal of the coupling interval of ventricular extrasystoles as an index of ectopic mechanisms. A mathematical model of modulated ventricular parasystole based on the relation between the coupling interval and the preceding RR interval was developed in an attempt to distinguish between parasystolic automaticity and other mechanisms. MATHEMATICAL MODEL: The relation between the coupling interval and the preceding RR interval was examined by plotting the coupling interval of each extrasystole against the preceding RR interval (coupling interval/RR diagram). The coupling interval/RR diagrams obtained from simulations with various modulation modes suggested that the parasystolic mechanism was likely when the dots representing extrasystoles appeared as discrete clusters. In contrast, a linear horizontal accumulation of dots indicated a non-parasystolic mechanism. To verify the validity of the simulations, 24 hour electrocardiographic recordings from 60 patients with frequent ventricular extrasystoles (> 1000/day) were analysed to determine whether the extrasystoles showed intrinsic periodicity. Intrinsic periodicity indicative of a parasystolic mechanism was seen in 14 (93%) of 15 patients in whom the coupling interval/RR diagram was characteristic of a parasystolic mechanism. When the coupling interval did not change (variability < 200 ms) over a wide range of RR intervals (> 700 ms) intrinsic periodicity was never identified (0/17). Parasystolic automaticity was the likely mechanism in 11 of the remaining 28 patients (39.3%) in whom coupling interval/RR diagrams were not definitive. These data indicate that definite patterns of coupling interval/RR diagrams can be used to distinguish between parasystolic and non-parasystolic mechanisms."} {"id": "PMID:1281662", "title": "In vitro displacement of vasoactive mediators from plasma proteins: a possible mechanism for pseudo-allergic reactions to neuromuscular blocking drugs.", "content": "We have studied the release of prostaglandin F2 alpha (PGF2 alpha) and histamine from serum proteins by neuromuscular blocking drugs using equilibrium dialysis, with tracer quantities of radio-labelled mediators as probes. Small concentrations (0.05-0.25 mmol litre-1) of competitive neuromuscular blocking drugs displaced 16-67% of bound histamine. Greater concentrations of suxamethonium (2 mmol litre-1) were required for histamine displacement (19%). There was a significant release of PGF2 alpha by atracurium 1 mmol litre-1 and pancuronium 0.69 mmol litre-1. These findings suggest an alternative mechanism of histamine release by neuromuscular blocking drugs which may be relevant to adverse reactions during use.", "contents": "In vitro displacement of vasoactive mediators from plasma proteins: a possible mechanism for pseudo-allergic reactions to neuromuscular blocking drugs. We have studied the release of prostaglandin F2 alpha (PGF2 alpha) and histamine from serum proteins by neuromuscular blocking drugs using equilibrium dialysis, with tracer quantities of radio-labelled mediators as probes. Small concentrations (0.05-0.25 mmol litre-1) of competitive neuromuscular blocking drugs displaced 16-67% of bound histamine. Greater concentrations of suxamethonium (2 mmol litre-1) were required for histamine displacement (19%). There was a significant release of PGF2 alpha by atracurium 1 mmol litre-1 and pancuronium 0.69 mmol litre-1. These findings suggest an alternative mechanism of histamine release by neuromuscular blocking drugs which may be relevant to adverse reactions during use."} {"id": "PMID:1281664", "title": "An immunohistochemical study of testicular biopsies in childhood acute lymphoblastic leukemia: reactivity of normal testicular components and leukemic infiltrates.", "content": "We performed an immunohistochemical analysis of frozen sections from testicular biopsies from 23 children with acute lymphoblastic leukemia. Eleven cases were infiltrated by leukemia. Tumor cells were immunostained by a panel of antibodies that identified CD10, CD43, CD19, CD3, CD7, and MHC class I and II. The immunoreactivity of normal testicular components was also studied. Normal testis showed no CD10 reactivity. Wide variation in the number of stromal macrophages identified by CD11c was found. Transferrin receptor (CD71) was expressed by some stromal macrophages, by seminiferous tubules, and by Leydig cells. B lymphocytes were absent from the testicular stroma but small numbers of T lymphocytes were consistently present. MHC class I and II were expressed by most stromal cells but not by seminiferous tubules.", "contents": "An immunohistochemical study of testicular biopsies in childhood acute lymphoblastic leukemia: reactivity of normal testicular components and leukemic infiltrates. We performed an immunohistochemical analysis of frozen sections from testicular biopsies from 23 children with acute lymphoblastic leukemia. Eleven cases were infiltrated by leukemia. Tumor cells were immunostained by a panel of antibodies that identified CD10, CD43, CD19, CD3, CD7, and MHC class I and II. The immunoreactivity of normal testicular components was also studied. Normal testis showed no CD10 reactivity. Wide variation in the number of stromal macrophages identified by CD11c was found. Transferrin receptor (CD71) was expressed by some stromal macrophages, by seminiferous tubules, and by Leydig cells. B lymphocytes were absent from the testicular stroma but small numbers of T lymphocytes were consistently present. MHC class I and II were expressed by most stromal cells but not by seminiferous tubules."} {"id": "PMID:1281665", "title": "H-ras and c-myc RNA expression in human T-cell ALL and in normal human lymphocytes.", "content": "We have compared the RNA expression of two oncogenes, H-ras and c-myc, with normal human lymphocytes, normal human T-cells, and human T-cell acute lymphoblastic leukemia (ALL). T-cell ALL RNA was derived from two human T-cell lines (MOLT-3 and CEM) and from five children with T-cell ALL. The RNA expression of H-ras and the third exon of c-myc was determined by northern hybridization. RNA from both MOLT-3 and CEM overexpressed both H-ras and the third exon of c-myc compared to normal lymphocytes and normal T-cells. T-cell ALL samples from four of five children overexpressed H-ras, while three of five patient samples overexpressed the third exon of c-myc when compared to normal lymphocytes and normal T-cells. Additional information on the oncogene expression of T-cell ALL may prove to be useful in the diagnosis and treatment of T-cell ALL.", "contents": "H-ras and c-myc RNA expression in human T-cell ALL and in normal human lymphocytes. We have compared the RNA expression of two oncogenes, H-ras and c-myc, with normal human lymphocytes, normal human T-cells, and human T-cell acute lymphoblastic leukemia (ALL). T-cell ALL RNA was derived from two human T-cell lines (MOLT-3 and CEM) and from five children with T-cell ALL. The RNA expression of H-ras and the third exon of c-myc was determined by northern hybridization. RNA from both MOLT-3 and CEM overexpressed both H-ras and the third exon of c-myc compared to normal lymphocytes and normal T-cells. T-cell ALL samples from four of five children overexpressed H-ras, while three of five patient samples overexpressed the third exon of c-myc when compared to normal lymphocytes and normal T-cells. Additional information on the oncogene expression of T-cell ALL may prove to be useful in the diagnosis and treatment of T-cell ALL."} {"id": "PMID:1281667", "title": "Quality of life measurements in anti-emetic trials: a discussion of Professor Selby's paper.", "content": "Our unit has not investigated quality of life measurements specifically, and therefore I would like to make some general comments on the presentations by Professor Selby and Dr. Lindley. There are a number of influencing factors which affect the quality of life of cancer patients. An effective anti-emetic reduces nausea and vomiting and this could have an impact on patient well-being during the period of cytotoxic treatment. The question is, 'Do new, more effective anti-emetics improve the overall quality of life of cancer patients?' In order to show this we need to define very carefully the patient population under consideration.", "contents": "Quality of life measurements in anti-emetic trials: a discussion of Professor Selby's paper. Our unit has not investigated quality of life measurements specifically, and therefore I would like to make some general comments on the presentations by Professor Selby and Dr. Lindley. There are a number of influencing factors which affect the quality of life of cancer patients. An effective anti-emetic reduces nausea and vomiting and this could have an impact on patient well-being during the period of cytotoxic treatment. The question is, 'Do new, more effective anti-emetics improve the overall quality of life of cancer patients?' In order to show this we need to define very carefully the patient population under consideration."} {"id": "PMID:1281666", "title": "Preoperative chemotherapy of cellular congenital mesoblastic nephroma in a 5-month-old infant.", "content": "Cellular (or atypical) congenital mesoblastic nephroma (CMN) is a potentially aggressive form of the benign classical congenital mesoblastic nephroma. We report here a case of cellular CMN in a 5-month-old boy treated preoperatively with chemotherapy with an excellent response allowing a complete surgical resection.", "contents": "Preoperative chemotherapy of cellular congenital mesoblastic nephroma in a 5-month-old infant. Cellular (or atypical) congenital mesoblastic nephroma (CMN) is a potentially aggressive form of the benign classical congenital mesoblastic nephroma. We report here a case of cellular CMN in a 5-month-old boy treated preoperatively with chemotherapy with an excellent response allowing a complete surgical resection."} {"id": "PMID:1281671", "title": "Prenatal diagnosis in a subset of trichothiodystrophy patients defective in DNA repair.", "content": "Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulphur content, and mental and physical retardation. Numerous additional clinical features may be present, producing a very heterogeneous syndrome. Many cases exhibit ichthyosis and photosensitivity. Cells from photosensitive TTD patients show reduced DNA repair levels similar to those found in xeroderma pigmentosum. TTD patients have a short life expectancy, and no treatment is known or envisaged. We report the prenatal diagnosis of TTD in two French families, based on DNA repair measurements in trophoblasts or amniotic cells, with later confirmation by microscopic analysis of the fetal hairs. Although the DNA repair defect was less marked in the fetal cells when compared with fibroblasts from the index case, measurement of DNA repair by unscheduled DNA synthesis provided unambiguous evidence of defective DNA repair in the fetal cells. This method is therefore a suitable prenatal diagnostic test for those TTD families in which a DNA repair defect has been identified.", "contents": "Prenatal diagnosis in a subset of trichothiodystrophy patients defective in DNA repair. Trichothiodystrophy (TTD) is an autosomal recessive disorder characterized by brittle hair with reduced sulphur content, and mental and physical retardation. Numerous additional clinical features may be present, producing a very heterogeneous syndrome. Many cases exhibit ichthyosis and photosensitivity. Cells from photosensitive TTD patients show reduced DNA repair levels similar to those found in xeroderma pigmentosum. TTD patients have a short life expectancy, and no treatment is known or envisaged. We report the prenatal diagnosis of TTD in two French families, based on DNA repair measurements in trophoblasts or amniotic cells, with later confirmation by microscopic analysis of the fetal hairs. Although the DNA repair defect was less marked in the fetal cells when compared with fibroblasts from the index case, measurement of DNA repair by unscheduled DNA synthesis provided unambiguous evidence of defective DNA repair in the fetal cells. This method is therefore a suitable prenatal diagnostic test for those TTD families in which a DNA repair defect has been identified."} {"id": "PMID:1281672", "title": "Nine years' experience of BELD combination chemotherapy (bleomycin, vindesine, CCNU and DTIC) for metastatic melanoma.", "content": "During the 9-year period from 1982 to 1991, 72 patients with melanoma were treated with a 5-day quadruple drug chemotherapy regime (BELD) comprising bleomycin, vindesine (Eldesine), CCNU (Lomustine) and DTIC. Forty-three patients had stage III melanoma, 34 of whom had evaluable disease. Of these 34, six (17.6%) achieved a complete response (CR), eight (23.5%) had a partial response (PR), five (14.7%) had stabilized disease (SD) and 15 (44.1%) had progressive disease (PD). Overall median survival of stage III melanoma patients was 38 weeks. Median survival of responders (CR + PR) was 47 weeks and 21 weeks for non-responders (SD + PD) (P < 0.005). Median follow-up time was 38 weeks. Following these encouraging results, 30 patients with stage II melanoma received BELD chemotherapy as adjuvant therapy after regional node dissection and clearance. Adjuvant BELD chemotherapy did not alter survival in these patients. BELD combination chemotherapy is well-tolerated, the main problems being nausea, vomiting, and leucopenia. We have maintained a combined response rate (CR + PR) of 41.1% for stage III disease. This is comparable with other combination chemotherapy regimes, which have as yet not been superseded by the newer biological therapies.", "contents": "Nine years' experience of BELD combination chemotherapy (bleomycin, vindesine, CCNU and DTIC) for metastatic melanoma. During the 9-year period from 1982 to 1991, 72 patients with melanoma were treated with a 5-day quadruple drug chemotherapy regime (BELD) comprising bleomycin, vindesine (Eldesine), CCNU (Lomustine) and DTIC. Forty-three patients had stage III melanoma, 34 of whom had evaluable disease. Of these 34, six (17.6%) achieved a complete response (CR), eight (23.5%) had a partial response (PR), five (14.7%) had stabilized disease (SD) and 15 (44.1%) had progressive disease (PD). Overall median survival of stage III melanoma patients was 38 weeks. Median survival of responders (CR + PR) was 47 weeks and 21 weeks for non-responders (SD + PD) (P < 0.005). Median follow-up time was 38 weeks. Following these encouraging results, 30 patients with stage II melanoma received BELD chemotherapy as adjuvant therapy after regional node dissection and clearance. Adjuvant BELD chemotherapy did not alter survival in these patients. BELD combination chemotherapy is well-tolerated, the main problems being nausea, vomiting, and leucopenia. We have maintained a combined response rate (CR + PR) of 41.1% for stage III disease. This is comparable with other combination chemotherapy regimes, which have as yet not been superseded by the newer biological therapies."} {"id": "PMID:1281674", "title": "FK506 and rapamycin selectively enhance degradation of IL-2 and GM-CSF mRNA.", "content": "The macrolides FK506 and rapamycin are potent immunosuppressive agents that inhibit the activation of T cells. Using Northern analyses and promoter-reporter constructs we analyzed the transcriptional and posttranscriptional effects of FK506 and rapamycin on IL-2, GM-CSF, and IL-2R alpha gene expression. FK506 completely inhibited activation of the IL-2 promoter, but only partially blocked GM-CSF promoter activity. In contrast, rapamycin only partially inhibited IL-2 and GM-CSF promoter activity. Interestingly, both FK506 and rapamycin also destabilized both IL-2 and GM-CSF mRNAs without influencing the stability of either the IL-2R alpha or GAPDH mRNA. These results show that both FK506 and rapamycin modulate IL-2 and GM-CSF gene expression at both the transcriptional and posttranscriptional level.", "contents": "FK506 and rapamycin selectively enhance degradation of IL-2 and GM-CSF mRNA. The macrolides FK506 and rapamycin are potent immunosuppressive agents that inhibit the activation of T cells. Using Northern analyses and promoter-reporter constructs we analyzed the transcriptional and posttranscriptional effects of FK506 and rapamycin on IL-2, GM-CSF, and IL-2R alpha gene expression. FK506 completely inhibited activation of the IL-2 promoter, but only partially blocked GM-CSF promoter activity. In contrast, rapamycin only partially inhibited IL-2 and GM-CSF promoter activity. Interestingly, both FK506 and rapamycin also destabilized both IL-2 and GM-CSF mRNAs without influencing the stability of either the IL-2R alpha or GAPDH mRNA. These results show that both FK506 and rapamycin modulate IL-2 and GM-CSF gene expression at both the transcriptional and posttranscriptional level."} {"id": "PMID:1281675", "title": "Pharmacokinetic parameters of recombinant mast cell growth factor (rMGF).", "content": "The gene product of the murine Steel (Sl) locus encodes an early-acting hematopoietic growth factor that is a ligand for the c-kit protooncogene. Several cDNAs for the Sl gene product, known as mast cell growth factor (MGF), stem cell factor (SCF), or kit ligand (KL), have recently been isolated, and both soluble and membrane-associated versions have been shown to be biologically active. The potential for therapeutic usage of recombinant MGF (rMGF) indicated a need for determining the biodistribution and elimination parameters of this cytokine. Pharmacokinetic studies demonstrated that radiolabeled rMGF had a distribution half-life of 2 min and an elimination half-life of 2.1 h in wild-type mice following iv injection, during which a striking localization of labeled rMGF in the lungs was noted. When administered by subcutaneous injection the elimination half-life was prolonged to 8.4 h. The primary sites of rMGF elimination appeared to be the kidneys and the liver. Pharmacokinetic analysis of labeled rMGF in mutant Sl/Sld mice, which are mast cell deficient, demonstrated similar distribution and elimination half-lives compared to wild-type mice (1.4 min and 1.8 h, respectively). In addition, the biodistribution pattern of the labeled rMGF in Sl/Sld mice was similar to that observed in wild-type mice, including the striking localization to the lungs. Binding of radiolabeled rMGF to lungs in vivo subsequent to iv injection was completely inhibited by excess unlabeled rMGF. Interestingly, mice that received an iv injection of the higher doses of rMGF (15 micrograms) demonstrated profound respiratory distress and hypotension within minutes of administration. Histologic analysis of lungs from such mice revealed extensive mast cell degranulation, which was associated with vasodilatation and pronounced hyperemia of virtually all pulmonary vessels. The respiratory distress in normal mice was probably a consequence of mast cell degranulation induced by rMGF since similar findings were not observed in Sl/Sld mice injected with identical concentrations of rMGF.", "contents": "Pharmacokinetic parameters of recombinant mast cell growth factor (rMGF). The gene product of the murine Steel (Sl) locus encodes an early-acting hematopoietic growth factor that is a ligand for the c-kit protooncogene. Several cDNAs for the Sl gene product, known as mast cell growth factor (MGF), stem cell factor (SCF), or kit ligand (KL), have recently been isolated, and both soluble and membrane-associated versions have been shown to be biologically active. The potential for therapeutic usage of recombinant MGF (rMGF) indicated a need for determining the biodistribution and elimination parameters of this cytokine. Pharmacokinetic studies demonstrated that radiolabeled rMGF had a distribution half-life of 2 min and an elimination half-life of 2.1 h in wild-type mice following iv injection, during which a striking localization of labeled rMGF in the lungs was noted. When administered by subcutaneous injection the elimination half-life was prolonged to 8.4 h. The primary sites of rMGF elimination appeared to be the kidneys and the liver. Pharmacokinetic analysis of labeled rMGF in mutant Sl/Sld mice, which are mast cell deficient, demonstrated similar distribution and elimination half-lives compared to wild-type mice (1.4 min and 1.8 h, respectively). In addition, the biodistribution pattern of the labeled rMGF in Sl/Sld mice was similar to that observed in wild-type mice, including the striking localization to the lungs. Binding of radiolabeled rMGF to lungs in vivo subsequent to iv injection was completely inhibited by excess unlabeled rMGF. Interestingly, mice that received an iv injection of the higher doses of rMGF (15 micrograms) demonstrated profound respiratory distress and hypotension within minutes of administration. Histologic analysis of lungs from such mice revealed extensive mast cell degranulation, which was associated with vasodilatation and pronounced hyperemia of virtually all pulmonary vessels. The respiratory distress in normal mice was probably a consequence of mast cell degranulation induced by rMGF since similar findings were not observed in Sl/Sld mice injected with identical concentrations of rMGF."} {"id": "PMID:1281673", "title": "Kinetics of endosomal acidification in Dictyostelium discoideum amoebae. 31P-NMR evidence for a very acidic early endosomal compartment.", "content": "We have examined the pH of the various endosomal compartments in the amoebae of the cellular slime mould Dictyostelium discoideum. This was accomplished both by fluorescence and by in vivo 31P-NMR methods. The fluid-phase marker, fluorescein-labeled dextran, was fed to the amoebae to report the average pH of their endocytic vesicles. During the progressive loading of successive endosomal compartments, we observed an early acidification down to a minimum value of pH < or = 5.3 after 30 min at 20 degrees C followed by an increase to an average pH of 5.8 when all the endosomal compartments were loaded by the fluid-phase marker. The weak fluorescence intensity of FITC-dextran at acidic pH precluded a more detailed investigation and we checked various phosphonate compounds as potential 31P-NMR pH probes for the endosomal compartments. Two molecules, aminomethylphosphonate and 2-aminoethylphosphonate, were selected for this study because of the large amplitudes of their chemical shift variation with pH (2 and 2.5 ppm, respectively) and their acidic pKs of 5.5 and 6.3, respectively. They were only moderately toxic (IC50% approximately 10 mM) towards both the axenic growth and the differentiation program of Dictyostelium amoebae. Internalization of the two aminophosphonates occurred only through the fluid-phase pinocytosis pathway as revealed by the full inhibition of their entry with 1 mM vanadate or 7.5 mM caffeine, two previously characterized inhibitors of endocytosis in Dictyostelium. We found that in vivo 31P-NMR of amoebae suspensions incubated with the aminophosphonates allowed the detection of three distinct intracellular compartments at pH 4.3, 5.8-6.0 and 7.3. Kinetics of aminophosphonate entry were analyzed and the results allowed us to reconstruct the time course for the acidification sequence during endocytosis. The data are consistent with the hypothesis that in Dictyostelium amoebae phosphonates occupy a highly acidic early endosomal compartment (t1/2 = 18 min; pH 4.3) before reaching a less acidic late endosomal/prelysosomal compartment (pH 5.8-6.0) from where they are immediately transported to, and trapped in, the cytoplasm (pH 7.3).", "contents": "Kinetics of endosomal acidification in Dictyostelium discoideum amoebae. 31P-NMR evidence for a very acidic early endosomal compartment. We have examined the pH of the various endosomal compartments in the amoebae of the cellular slime mould Dictyostelium discoideum. This was accomplished both by fluorescence and by in vivo 31P-NMR methods. The fluid-phase marker, fluorescein-labeled dextran, was fed to the amoebae to report the average pH of their endocytic vesicles. During the progressive loading of successive endosomal compartments, we observed an early acidification down to a minimum value of pH < or = 5.3 after 30 min at 20 degrees C followed by an increase to an average pH of 5.8 when all the endosomal compartments were loaded by the fluid-phase marker. The weak fluorescence intensity of FITC-dextran at acidic pH precluded a more detailed investigation and we checked various phosphonate compounds as potential 31P-NMR pH probes for the endosomal compartments. Two molecules, aminomethylphosphonate and 2-aminoethylphosphonate, were selected for this study because of the large amplitudes of their chemical shift variation with pH (2 and 2.5 ppm, respectively) and their acidic pKs of 5.5 and 6.3, respectively. They were only moderately toxic (IC50% approximately 10 mM) towards both the axenic growth and the differentiation program of Dictyostelium amoebae. Internalization of the two aminophosphonates occurred only through the fluid-phase pinocytosis pathway as revealed by the full inhibition of their entry with 1 mM vanadate or 7.5 mM caffeine, two previously characterized inhibitors of endocytosis in Dictyostelium. We found that in vivo 31P-NMR of amoebae suspensions incubated with the aminophosphonates allowed the detection of three distinct intracellular compartments at pH 4.3, 5.8-6.0 and 7.3. Kinetics of aminophosphonate entry were analyzed and the results allowed us to reconstruct the time course for the acidification sequence during endocytosis. The data are consistent with the hypothesis that in Dictyostelium amoebae phosphonates occupy a highly acidic early endosomal compartment (t1/2 = 18 min; pH 4.3) before reaching a less acidic late endosomal/prelysosomal compartment (pH 5.8-6.0) from where they are immediately transported to, and trapped in, the cytoplasm (pH 7.3)."} {"id": "PMID:1281676", "title": "Differential oncolytic effect of NK-enriched subsets in long-term interleukin-2 cultures.", "content": "The aim of this study was to characterize the oncolytic efficacy of human natural killer (NK) cell subsets generated from highly NK-enriched population in long-term IL-2 cultures. NK cells cultured for 3 weeks with interleukin-2 (IL-2) were separated into several subsets using two color fluorescence-activated cell sorting and CD2, CD8, CD16, and CD56 monoclonal antibodies. These individual NK cell subsets were then tested for cytotoxicity against various tumor target cell lines, including K-562, Daudi, and Ovcar-3. The CD16+/CD56+ NK cell subset was superior in its cytotoxic activity against all targets in comparison to the CD16-/CD56+ subset. Within CD16 population, CD16+CD2+ NK cells were most potent; however CD16+/CD2- subset was also cytotoxic, indicating that CD2 molecule is important, but not necessary for NK cell cytotoxic function. CD16+/CD8+ and CD16+/CD8- subsets showed variance in cytolytic efficacy, depending on the tumor target tested. Highest cytotoxicity against K-562 was observed in the CD16+/CD8+ population, while the CD16+/CD8- subset manifested highest cytotoxic activity against Daudi. No significant differences within these NK cell subsets were observed against Ovcar-3 targets. These data indicate that NK cell subsets are not equally oncolytic, and that the oncolytic effect may be tumor dependent.", "contents": "Differential oncolytic effect of NK-enriched subsets in long-term interleukin-2 cultures. The aim of this study was to characterize the oncolytic efficacy of human natural killer (NK) cell subsets generated from highly NK-enriched population in long-term IL-2 cultures. NK cells cultured for 3 weeks with interleukin-2 (IL-2) were separated into several subsets using two color fluorescence-activated cell sorting and CD2, CD8, CD16, and CD56 monoclonal antibodies. These individual NK cell subsets were then tested for cytotoxicity against various tumor target cell lines, including K-562, Daudi, and Ovcar-3. The CD16+/CD56+ NK cell subset was superior in its cytotoxic activity against all targets in comparison to the CD16-/CD56+ subset. Within CD16 population, CD16+CD2+ NK cells were most potent; however CD16+/CD2- subset was also cytotoxic, indicating that CD2 molecule is important, but not necessary for NK cell cytotoxic function. CD16+/CD8+ and CD16+/CD8- subsets showed variance in cytolytic efficacy, depending on the tumor target tested. Highest cytotoxicity against K-562 was observed in the CD16+/CD8+ population, while the CD16+/CD8- subset manifested highest cytotoxic activity against Daudi. No significant differences within these NK cell subsets were observed against Ovcar-3 targets. These data indicate that NK cell subsets are not equally oncolytic, and that the oncolytic effect may be tumor dependent."} {"id": "PMID:1281677", "title": "Elevated levels of acute phase plasma proteins in major depression.", "content": "Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression.", "contents": "Elevated levels of acute phase plasma proteins in major depression. Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression."} {"id": "PMID:1281678", "title": "Facial nerve transection causes expansion of myelin autoreactive T cells in regional lymph nodes and T cell homing to the facial nucleus.", "content": "Nervous tissue expression of immunological signal and recognition molecules, as well as lymphoid tissue immune responses after facial nerve trauma was studied in male rats of the Lewis and Brown Norway (BN) strains. In both rat strains nerve transection caused within four days the appearance of IFN-gamma-like immunoreactivity in the cytoplasm of axotomized motor neurons and an induction of MHC class I and II, and CD4 molecules on surrounding glial cells to a similar extent. T lymphocytes also infiltrated the facial nuclei ipsilateral to the axotomy in all animals. The number of autoreactive T cells in superficial cervical lymph nodes, which in response to whole myelin or peptides of myelin basic protein (MBP) secreted IFN-gamma increased markedly after axotomy. This response was more conspicuous in Lewis rats, which are susceptible to experimental allergic encephalomyelitis (EAE), than in BN rats, which are EAE resistant. A proportion of the axotomized Lewis rats also developed widespread perivascular infiltration of mononuclear cells in the CNS, reminiscent of EAE. Hypothetically, a strong expansion of myelin autoreactive IFN-gamma producing T cells secondary to nerve trauma may have immunopathological consequences in genetically predisposed individuals. It is also possible that myelin reactive T cells, whether recruited to the lesioned nerve, could have impact on macrophage function during Wallerian degeneration in the distal stump.", "contents": "Facial nerve transection causes expansion of myelin autoreactive T cells in regional lymph nodes and T cell homing to the facial nucleus. Nervous tissue expression of immunological signal and recognition molecules, as well as lymphoid tissue immune responses after facial nerve trauma was studied in male rats of the Lewis and Brown Norway (BN) strains. In both rat strains nerve transection caused within four days the appearance of IFN-gamma-like immunoreactivity in the cytoplasm of axotomized motor neurons and an induction of MHC class I and II, and CD4 molecules on surrounding glial cells to a similar extent. T lymphocytes also infiltrated the facial nuclei ipsilateral to the axotomy in all animals. The number of autoreactive T cells in superficial cervical lymph nodes, which in response to whole myelin or peptides of myelin basic protein (MBP) secreted IFN-gamma increased markedly after axotomy. This response was more conspicuous in Lewis rats, which are susceptible to experimental allergic encephalomyelitis (EAE), than in BN rats, which are EAE resistant. A proportion of the axotomized Lewis rats also developed widespread perivascular infiltration of mononuclear cells in the CNS, reminiscent of EAE. Hypothetically, a strong expansion of myelin autoreactive IFN-gamma producing T cells secondary to nerve trauma may have immunopathological consequences in genetically predisposed individuals. It is also possible that myelin reactive T cells, whether recruited to the lesioned nerve, could have impact on macrophage function during Wallerian degeneration in the distal stump."} {"id": "PMID:1281679", "title": "Effects of acyl chain length on the conformation of myelin basic protein bound to lysolipid micelles.", "content": "The interactions of myelin basic protein with micelles of lysophosphatidylcholine detergents of different acyl chain lengths were investigated by circular dichroism (CD), small-angle X-ray scattering, Fourier transform infrared spectroscopy (FT-IR), and 1H, 13C and 31P nuclear magnetic resonance spectroscopy (NMR). Circular dichroic, FT-IR, and 1H NMR measurements indicated that the conformational changes induced in the protein molecules by association with micelles depended on the acyl chain length of the detergents. Size is one of the physical properties of micelles which is a function of the length of the acyl chains. The radii of gyration of detergent micelles in complexes with the protein measured by small-angle X-ray scattering indicated that the average size of the micelles was a quadratic function of the acyl chain length. The dependence of the protein conformational changes on micelle size was used to ascertain the order in which different protein segments associate with the detergents. Several procedures were employed to change the fluidity of micelles formed with detergents of given acyl chain lengths. The conformational changes observed on the MBP molecule by varying the micelle properties without changing the length of the chain, suggested that the changes depended on the size and fluidity of the micelles.", "contents": "Effects of acyl chain length on the conformation of myelin basic protein bound to lysolipid micelles. The interactions of myelin basic protein with micelles of lysophosphatidylcholine detergents of different acyl chain lengths were investigated by circular dichroism (CD), small-angle X-ray scattering, Fourier transform infrared spectroscopy (FT-IR), and 1H, 13C and 31P nuclear magnetic resonance spectroscopy (NMR). Circular dichroic, FT-IR, and 1H NMR measurements indicated that the conformational changes induced in the protein molecules by association with micelles depended on the acyl chain length of the detergents. Size is one of the physical properties of micelles which is a function of the length of the acyl chains. The radii of gyration of detergent micelles in complexes with the protein measured by small-angle X-ray scattering indicated that the average size of the micelles was a quadratic function of the acyl chain length. The dependence of the protein conformational changes on micelle size was used to ascertain the order in which different protein segments associate with the detergents. Several procedures were employed to change the fluidity of micelles formed with detergents of given acyl chain lengths. The conformational changes observed on the MBP molecule by varying the micelle properties without changing the length of the chain, suggested that the changes depended on the size and fluidity of the micelles."} {"id": "PMID:1281680", "title": "[The biopolymer metabolism of the connective tissue in the aorta under intraventricular injections of neuropeptides].", "content": "The metabolism of connective tissue biopolymers in the blood serum and in the aorta under repeated intraventricular injections of P-substance, L-enkephalin and B-endorphine was studied in chronic experiments on rabbits. The alternations of the central neurochemical processes, caused by prolonged intraventricular injections of neuropeptides were proved to lead to intensification of metabolic processes in the connective tissue characterized by the accumulation of its biopolymers in the aorta wall. The injection of P-substance, in contrast to opioid peptides, is accompanied by more marked alternations.", "contents": "[The biopolymer metabolism of the connective tissue in the aorta under intraventricular injections of neuropeptides]. The metabolism of connective tissue biopolymers in the blood serum and in the aorta under repeated intraventricular injections of P-substance, L-enkephalin and B-endorphine was studied in chronic experiments on rabbits. The alternations of the central neurochemical processes, caused by prolonged intraventricular injections of neuropeptides were proved to lead to intensification of metabolic processes in the connective tissue characterized by the accumulation of its biopolymers in the aorta wall. The injection of P-substance, in contrast to opioid peptides, is accompanied by more marked alternations."} {"id": "PMID:1281681", "title": "[Keratin metabolism in the epidermis and hair of mice with experimental diabetes].", "content": "An animal trial was performed using mice with streptozotocine-induced diabetes, with investigation of velocity of prekeratin and keratin biosynthesis and degradation using 14C-glycine, and evaluation of the content of -SH and -S-S groups in epidermal prekeratin. It has been found out that velocity of epidermal prekeratin and keratin in diabetic animals is higher than that in healthy group. SS and SH groups ratio in prekeratin in diabetic animals is 10 times as high as that in the control group. In the hair of diabetic mice an increased keratin turnover was observed as compared with the norm. The data testify that experimental diabetes manifests itself in increased intensity of keratin metabolism in epidermis and hair. These results may be used as the criteria in elaboration of non-invasive methods for diabetes diagnosis.", "contents": "[Keratin metabolism in the epidermis and hair of mice with experimental diabetes]. An animal trial was performed using mice with streptozotocine-induced diabetes, with investigation of velocity of prekeratin and keratin biosynthesis and degradation using 14C-glycine, and evaluation of the content of -SH and -S-S groups in epidermal prekeratin. It has been found out that velocity of epidermal prekeratin and keratin in diabetic animals is higher than that in healthy group. SS and SH groups ratio in prekeratin in diabetic animals is 10 times as high as that in the control group. In the hair of diabetic mice an increased keratin turnover was observed as compared with the norm. The data testify that experimental diabetes manifests itself in increased intensity of keratin metabolism in epidermis and hair. These results may be used as the criteria in elaboration of non-invasive methods for diabetes diagnosis."} {"id": "PMID:1281682", "title": "Role of human immunodeficiency virus replication in defective in vitro growth of hematopoietic progenitors.", "content": "A number of hematologic abnormalities, including cytopenias, have been observed in patients with human immunodeficiency virus (HIV) infection. To elucidate their mechanisms, a group of 27 patients with HIV-1 infection was studied. In all patients, a marked reduction of in vitro colony formation by erythroid, granulomacrophagic, and megakaryocytic bone marrow progenitors was observed in comparison to normal donors. HIV-1 infection of marrow progenitors was investigated in studying individual colonies with the polymerase chain reaction (PCR) technique. No HIV-1 DNA could be detected in these colonies, suggesting either that marrow progenitors were not infected or that infected progenitors were not able to generate colonies in vitro. The addition of antisense oligonucleotides directed against HIV tat or nef sequences in the culture medium led to a significant increase in colony formation, suggesting that HIV replication in hematopoietic progenitors could be responsible for their defective growth. However, no HIV-1-infected colonies could be detected by PCR after the antisense treatment, indicating that the increase in colony number was not due to the proliferation and differentiation of infected progenitors but to an inhibition of HIV replication in an accessory cell. This last hypothesis was further confirmed by the absence of effects of antisense oligomers on the plating efficiency of hematopoietic progenitors grown from CD34+ cells. These data indicate that hematologic abnormalities of HIV-infected patients cannot be explained by a direct infection of hematopoietic progenitor cells and suggest that a defective modulation of progenitor cell growth by HIV replication outside these cells might play a role in these abnormalities.", "contents": "Role of human immunodeficiency virus replication in defective in vitro growth of hematopoietic progenitors. A number of hematologic abnormalities, including cytopenias, have been observed in patients with human immunodeficiency virus (HIV) infection. To elucidate their mechanisms, a group of 27 patients with HIV-1 infection was studied. In all patients, a marked reduction of in vitro colony formation by erythroid, granulomacrophagic, and megakaryocytic bone marrow progenitors was observed in comparison to normal donors. HIV-1 infection of marrow progenitors was investigated in studying individual colonies with the polymerase chain reaction (PCR) technique. No HIV-1 DNA could be detected in these colonies, suggesting either that marrow progenitors were not infected or that infected progenitors were not able to generate colonies in vitro. The addition of antisense oligonucleotides directed against HIV tat or nef sequences in the culture medium led to a significant increase in colony formation, suggesting that HIV replication in hematopoietic progenitors could be responsible for their defective growth. However, no HIV-1-infected colonies could be detected by PCR after the antisense treatment, indicating that the increase in colony number was not due to the proliferation and differentiation of infected progenitors but to an inhibition of HIV replication in an accessory cell. This last hypothesis was further confirmed by the absence of effects of antisense oligomers on the plating efficiency of hematopoietic progenitors grown from CD34+ cells. These data indicate that hematologic abnormalities of HIV-infected patients cannot be explained by a direct infection of hematopoietic progenitor cells and suggest that a defective modulation of progenitor cell growth by HIV replication outside these cells might play a role in these abnormalities."} {"id": "PMID:1281683", "title": "Effect of stem cell factor on in vitro erythropoiesis in patients with bone marrow failure syndromes.", "content": "Stem cell factor (SCF) enhances normal hematopoiesis. We examined its effect in vitro on bone marrow and blood progenitors from patients with inherited bone marrow failure syndromes, including 17 patients each with Diamond-Blackfan anemia (DBA) and Fanconi's anemia (FA), 3 with dyskeratosis congenita (DC), and 1 each with amegakaryocytic thrombocytopenia (amega) and transient erythroblastopenia of childhood (TEC). Mononuclear cells were cultured with erythropoietin (Ep) alone or combined with SCF or other factors. SCF increased the growth of erythroid progenitors in cultures from 50% of normal controls, 90% of DBA, 70% of FA, 30% of DC, and the amega and TEC patients; normal numbers were reached in 25% of DBA studies. Improved in vitro erythropoiesis with SCF in all types of inherited marrow failure syndromes does not suggest a common defect involving kit or SCF, but implies that SCF may be helpful in the treatment of hematopoietic defects of varied etiologies.", "contents": "Effect of stem cell factor on in vitro erythropoiesis in patients with bone marrow failure syndromes. Stem cell factor (SCF) enhances normal hematopoiesis. We examined its effect in vitro on bone marrow and blood progenitors from patients with inherited bone marrow failure syndromes, including 17 patients each with Diamond-Blackfan anemia (DBA) and Fanconi's anemia (FA), 3 with dyskeratosis congenita (DC), and 1 each with amegakaryocytic thrombocytopenia (amega) and transient erythroblastopenia of childhood (TEC). Mononuclear cells were cultured with erythropoietin (Ep) alone or combined with SCF or other factors. SCF increased the growth of erythroid progenitors in cultures from 50% of normal controls, 90% of DBA, 70% of FA, 30% of DC, and the amega and TEC patients; normal numbers were reached in 25% of DBA studies. Improved in vitro erythropoiesis with SCF in all types of inherited marrow failure syndromes does not suggest a common defect involving kit or SCF, but implies that SCF may be helpful in the treatment of hematopoietic defects of varied etiologies."} {"id": "PMID:1281684", "title": "Recombinant human stem cell factor stimulates differentiation of mast cells from dispersed human fetal liver cells.", "content": "We have previously shown the development in vitro of tryptase+ human mast cells from fetal liver cells cocultured with murine 3T3 fibroblasts. In this study, recombinant human stem cell factor (rhuSCF), the ligand for the c-kit proto-oncogene product called Kit, stimulated the growth and differentiation primarily of mast cells from dispersed fetal liver cells, whereas recombinant human interleukin-3 (rhuIL-3) stimulated the differentiation of basophils along with other cell types. Cultures of fetal liver cells were initiated and maintained in the presence of rhuSCF or rhuIL-3 for up to 6 weeks. Metachromatic cells in cytospins were identified as mast cells primarily on the basis of tryptase expression, and as MCT or MCTC by immunohistochemistry using monoclonal antibodies against tryptase and chymase, whereas basophils were metachromatic, polymorphonuclear, and lacked these proteases. Levels of tryptase and histamine were measured by radioimmunoassay, tryptase and chymase activities by peptide hydrolysis, and cell surface Kit by flow cytometry with the monoclonal antibody YB5.B8. The predominant presence of mast cells occurred only in the cultures supplemented with rhuSCF. The percentage and total number of mast cells increased over time with increasing concentrations of rhuSCF and reached a plateau at 55 ng/mL. At this concentration of rhuSCF, mast cells first appeared by day 7; by day 42, 106% of the starting number of cells were present and 85% of these were tryptase+, 31% being weakly chymase+. These mast cells appeared immature by ultrastructural criteria; most cells were mononuclear, but some had nuclei with deeply divided lobes. DNA synthesis in tryptase+ mast cells at days 21 and 28 of culture with rhuSCF was demonstrated by incorporation of bromodeoxyuridine. Calculated levels of histamine (1.2 pg/mast cell) and tryptase (0.9 pg/mast cell) were similar to those determined previously in coculture experiments with murine 3T3 fibroblasts. Chymase activity was undetectable in most cell extracts. On day 0, 4% to 20% of fetal liver cells expressed cell surface Kit. In the presence of rhuSCF, the percentages and total numbers of Kit+ cells and the apparent concentration of Kit per cell increased along with the number of tryptase+ cells. In the presence of rhuIL-3, toluidine blue+, tryptase- cells first and maximally appeared at day 14 (11% +/- 2.5%). The percentage of these toluidine blue+ cells then declined to about 6% by days 21 and 35, while the total number of positive cells declined over 10-fold. Kit+ cells in the presence of rhuIL-3 declined from 9% on day 3 to 2% on day 35.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Recombinant human stem cell factor stimulates differentiation of mast cells from dispersed human fetal liver cells. We have previously shown the development in vitro of tryptase+ human mast cells from fetal liver cells cocultured with murine 3T3 fibroblasts. In this study, recombinant human stem cell factor (rhuSCF), the ligand for the c-kit proto-oncogene product called Kit, stimulated the growth and differentiation primarily of mast cells from dispersed fetal liver cells, whereas recombinant human interleukin-3 (rhuIL-3) stimulated the differentiation of basophils along with other cell types. Cultures of fetal liver cells were initiated and maintained in the presence of rhuSCF or rhuIL-3 for up to 6 weeks. Metachromatic cells in cytospins were identified as mast cells primarily on the basis of tryptase expression, and as MCT or MCTC by immunohistochemistry using monoclonal antibodies against tryptase and chymase, whereas basophils were metachromatic, polymorphonuclear, and lacked these proteases. Levels of tryptase and histamine were measured by radioimmunoassay, tryptase and chymase activities by peptide hydrolysis, and cell surface Kit by flow cytometry with the monoclonal antibody YB5.B8. The predominant presence of mast cells occurred only in the cultures supplemented with rhuSCF. The percentage and total number of mast cells increased over time with increasing concentrations of rhuSCF and reached a plateau at 55 ng/mL. At this concentration of rhuSCF, mast cells first appeared by day 7; by day 42, 106% of the starting number of cells were present and 85% of these were tryptase+, 31% being weakly chymase+. These mast cells appeared immature by ultrastructural criteria; most cells were mononuclear, but some had nuclei with deeply divided lobes. DNA synthesis in tryptase+ mast cells at days 21 and 28 of culture with rhuSCF was demonstrated by incorporation of bromodeoxyuridine. Calculated levels of histamine (1.2 pg/mast cell) and tryptase (0.9 pg/mast cell) were similar to those determined previously in coculture experiments with murine 3T3 fibroblasts. Chymase activity was undetectable in most cell extracts. On day 0, 4% to 20% of fetal liver cells expressed cell surface Kit. In the presence of rhuSCF, the percentages and total numbers of Kit+ cells and the apparent concentration of Kit per cell increased along with the number of tryptase+ cells. In the presence of rhuIL-3, toluidine blue+, tryptase- cells first and maximally appeared at day 14 (11% +/- 2.5%). The percentage of these toluidine blue+ cells then declined to about 6% by days 21 and 35, while the total number of positive cells declined over 10-fold. Kit+ cells in the presence of rhuIL-3 declined from 9% on day 3 to 2% on day 35.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281685", "title": "Expression of CD34 and platelet glycoproteins during human megakaryocytic differentiation.", "content": "Megakaryocyte (MK) progenitors express the CD34 antigen, but the precise stage along the MK differentiation at which the CD34 is turned off is not known. Purified marrow CD34+ cells give rise within 4 days in culture to rare mature MK, suggesting that some MK precursors bear the CD34 antigen. By multiparameter flow cytometry, CD34+ cells bearing platelet glycoproteins (GP) could be detected, but at a low frequency (less than 2% of the marrow CD34+ cells). We used an in vitro liquid suspension culture to selectively amplify MK differentiation. CD34+ cells were isolated after 6 days before a wave of mature MK. These cells gave rise within another 4 days in culture to numerous MK (up to 50%), showing that these CD34+ cells were greatly enriched in MK precursors. This was confirmed by ultrastructural studies that showed the presence of typical promegakaryoblasts. By flow cytometry, three populations of small cell size could be defined: CD34+ GPIIIa-, CD34+ GPIIIa+, and CD34- GPIIIa+ cells. The two GPIIIa+ populations were almost pure immature blastic MK. alpha-Granules were rare in the CD34+ GPIIIa+ cells, whereas they were more developed in the CD34- GPIIIa+ cells, which also exhibited demarcation membranes. Approximately 45% of the two GPIIIa+ cell populations were capable of undergoing at least one cell division and of giving rise to a polyploid progeny. However, proliferation and polyploidization capacities were higher in the CD34+ GPIIIa+ than in the CD34- GPIIIa+ cells. A small fraction of GPIIIa+ cells (about 10%) were able to give rise to MK colonies containing a maximum of 16 cells for the double-positive cells. GPIb was expressed on about sixfold less cells than GPIIIa, but was detected on a few CD34+ cells. Most double-stained (CD34+ GPIb+) cells were polyploid. CD34- GP+ cells (more mature) contained less polyploid MK than the CD34+ GP+ fraction. Altogether, these findings show that CD34 is still expressed on a polyploid transitional immature MK and that GPIIIa is present on some MK progenitors with low proliferative capacities. They also suggest that the expression of CD34 is related to the ability of the MK precursors to accomplish DNA synthesis (either cell division or endomitosis). Such a characterization will facilitate the investigation of the role of the different cytokines on MK differentiation.", "contents": "Expression of CD34 and platelet glycoproteins during human megakaryocytic differentiation. Megakaryocyte (MK) progenitors express the CD34 antigen, but the precise stage along the MK differentiation at which the CD34 is turned off is not known. Purified marrow CD34+ cells give rise within 4 days in culture to rare mature MK, suggesting that some MK precursors bear the CD34 antigen. By multiparameter flow cytometry, CD34+ cells bearing platelet glycoproteins (GP) could be detected, but at a low frequency (less than 2% of the marrow CD34+ cells). We used an in vitro liquid suspension culture to selectively amplify MK differentiation. CD34+ cells were isolated after 6 days before a wave of mature MK. These cells gave rise within another 4 days in culture to numerous MK (up to 50%), showing that these CD34+ cells were greatly enriched in MK precursors. This was confirmed by ultrastructural studies that showed the presence of typical promegakaryoblasts. By flow cytometry, three populations of small cell size could be defined: CD34+ GPIIIa-, CD34+ GPIIIa+, and CD34- GPIIIa+ cells. The two GPIIIa+ populations were almost pure immature blastic MK. alpha-Granules were rare in the CD34+ GPIIIa+ cells, whereas they were more developed in the CD34- GPIIIa+ cells, which also exhibited demarcation membranes. Approximately 45% of the two GPIIIa+ cell populations were capable of undergoing at least one cell division and of giving rise to a polyploid progeny. However, proliferation and polyploidization capacities were higher in the CD34+ GPIIIa+ than in the CD34- GPIIIa+ cells. A small fraction of GPIIIa+ cells (about 10%) were able to give rise to MK colonies containing a maximum of 16 cells for the double-positive cells. GPIb was expressed on about sixfold less cells than GPIIIa, but was detected on a few CD34+ cells. Most double-stained (CD34+ GPIb+) cells were polyploid. CD34- GP+ cells (more mature) contained less polyploid MK than the CD34+ GP+ fraction. Altogether, these findings show that CD34 is still expressed on a polyploid transitional immature MK and that GPIIIa is present on some MK progenitors with low proliferative capacities. They also suggest that the expression of CD34 is related to the ability of the MK precursors to accomplish DNA synthesis (either cell division or endomitosis). Such a characterization will facilitate the investigation of the role of the different cytokines on MK differentiation."} {"id": "PMID:1281686", "title": "tat protein stimulates production of transforming growth factor-beta 1 by marrow macrophages: a potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression.", "content": "In this study, we examined the potential role of the human immunodeficiency virus (HIV) tat protein in causing the hematopoietic abnormalities frequently observed in HIV-infected individuals. Recombinant tat (r-tat) protein, at concentrations up to 10 micrograms/mL, did not display any stimulatory or inhibitory effect on the survival/proliferative capacity of CD34+ hematopoietic progenitor cells, purified from normal bone marrow (BM). However, exposure of r-tat protein (at concentrations between 10 ng/mL and 10 micrograms/mL) to enriched normal BM macrophages induced the production of a factor(s) in conditioned media that inhibited the in vitro growth of CD34+ cells in liquid cultures and of immature hematopoietic progenitors (day 14 colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid, and colony-forming unit-megakaryocyte) in semisolid assays. Pre-exposure of r-tat protein with a monoclonal neutralizing anti-tat antibody completely abrogated the inhibitory activity present in BM macrophage culture supernatants. The main factor responsible for this suppressive activity was transforming growth factor-beta 1 (TGF-beta 1), as shown by the ability of a polyclonal anti-TGF-beta 1 neutralizing antibody to almost completely reverse the suppressive effect of BM macrophage supernatants on CD34+ cells. TGF-beta 1 bioassays showed that exposure of r-tat protein to BM macrophages significantly increased the levels of both active and latent forms of TGF-beta 1. These results indicate that the production of TGF-beta 1, one of the most potent negative regulator of hematopoiesis, is increased by HIV tat protein and that such increase could contribute to the derangement of the hematopoietic system in HIV-infected individuals.", "contents": "tat protein stimulates production of transforming growth factor-beta 1 by marrow macrophages: a potential mechanism for human immunodeficiency virus-1-induced hematopoietic suppression. In this study, we examined the potential role of the human immunodeficiency virus (HIV) tat protein in causing the hematopoietic abnormalities frequently observed in HIV-infected individuals. Recombinant tat (r-tat) protein, at concentrations up to 10 micrograms/mL, did not display any stimulatory or inhibitory effect on the survival/proliferative capacity of CD34+ hematopoietic progenitor cells, purified from normal bone marrow (BM). However, exposure of r-tat protein (at concentrations between 10 ng/mL and 10 micrograms/mL) to enriched normal BM macrophages induced the production of a factor(s) in conditioned media that inhibited the in vitro growth of CD34+ cells in liquid cultures and of immature hematopoietic progenitors (day 14 colony-forming unit-granulocyte-macrophage, burst-forming unit-erythroid, and colony-forming unit-megakaryocyte) in semisolid assays. Pre-exposure of r-tat protein with a monoclonal neutralizing anti-tat antibody completely abrogated the inhibitory activity present in BM macrophage culture supernatants. The main factor responsible for this suppressive activity was transforming growth factor-beta 1 (TGF-beta 1), as shown by the ability of a polyclonal anti-TGF-beta 1 neutralizing antibody to almost completely reverse the suppressive effect of BM macrophage supernatants on CD34+ cells. TGF-beta 1 bioassays showed that exposure of r-tat protein to BM macrophages significantly increased the levels of both active and latent forms of TGF-beta 1. These results indicate that the production of TGF-beta 1, one of the most potent negative regulator of hematopoiesis, is increased by HIV tat protein and that such increase could contribute to the derangement of the hematopoietic system in HIV-infected individuals."} {"id": "PMID:1281687", "title": "In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells.", "content": "c-kit is expressed on hematopoietic stem cells and progenitor cells, but not on lymphohematopoietic differentiated cells. Lineage marker-negative, c-kit-positive (Lin-c-kit+) bone marrow cells were fractionated by means of Ly6A/E or Sca-1 expression. Lin-c-kit+Sca-1+ cells, which consisted of 0.08% of bone marrow nucleated cells, did not contain day-8 colony-forming units-spleen (CFU-S), but 80% were day-12 CFU-S. One hundred cells rescued the lethally irradiated mice and reconstituted hematopoiesis. On the other hand, 2 x 10(3) of Lin-c-kit+Sca-1- cells formed 20 day-8 and 11 day-12 spleen colonies, but they could not rescue the lethally irradiated mice. These data indicate that Lin-c-kit+Sca-1+ cells are primitive hematopoietic stem cells and that Sca-1-cells do not contain stem cells that reconstitute hematopoiesis. Lin-c-kit+Sca-1+ cells formed no colonies in the presence of stem cell factor (SCF) or interleukin-6 (IL-6), and only 10% of them formed colonies in the presence of IL-3. However, approximately 50% of them formed large colonies in the presence of IL-3, IL-6, and SCF. Moreover, when single cells were deposited into culture medium by fluorescence-activated cell sorter clone sorting system, 40% of them proliferated on a stromal cell line (PA-6) and proliferated for more than 2 weeks. In contrast, 15% of the Lin-c-kit+Sca-1-cells formed colonies in the presence of IL-3, but no synergistic effects were observed in combination with SCF plus IL-6 and/or IL-3. Approximately 10% proliferated on PA-6, but most of them degenerated within 2 weeks. The population ratio of c-kit+Sca-1+ to c-kit+Sca-1- increased 2 and 4 days after exposure to 5-fluorouracil (5-FU). These results are consistent with the relative enrichment of highly proliferative colony-forming cells by 5-FU. These data show that, although c-kit is found both on the primitive hematopoietic stem cells and progenitors, Sca-1+ cells are more primitive and respond better than Sca-1- cells to a combination of hematopoietic factors, including SCF and stromal cells.", "contents": "In vivo and in vitro stem cell function of c-kit- and Sca-1-positive murine hematopoietic cells. c-kit is expressed on hematopoietic stem cells and progenitor cells, but not on lymphohematopoietic differentiated cells. Lineage marker-negative, c-kit-positive (Lin-c-kit+) bone marrow cells were fractionated by means of Ly6A/E or Sca-1 expression. Lin-c-kit+Sca-1+ cells, which consisted of 0.08% of bone marrow nucleated cells, did not contain day-8 colony-forming units-spleen (CFU-S), but 80% were day-12 CFU-S. One hundred cells rescued the lethally irradiated mice and reconstituted hematopoiesis. On the other hand, 2 x 10(3) of Lin-c-kit+Sca-1- cells formed 20 day-8 and 11 day-12 spleen colonies, but they could not rescue the lethally irradiated mice. These data indicate that Lin-c-kit+Sca-1+ cells are primitive hematopoietic stem cells and that Sca-1-cells do not contain stem cells that reconstitute hematopoiesis. Lin-c-kit+Sca-1+ cells formed no colonies in the presence of stem cell factor (SCF) or interleukin-6 (IL-6), and only 10% of them formed colonies in the presence of IL-3. However, approximately 50% of them formed large colonies in the presence of IL-3, IL-6, and SCF. Moreover, when single cells were deposited into culture medium by fluorescence-activated cell sorter clone sorting system, 40% of them proliferated on a stromal cell line (PA-6) and proliferated for more than 2 weeks. In contrast, 15% of the Lin-c-kit+Sca-1-cells formed colonies in the presence of IL-3, but no synergistic effects were observed in combination with SCF plus IL-6 and/or IL-3. Approximately 10% proliferated on PA-6, but most of them degenerated within 2 weeks. The population ratio of c-kit+Sca-1+ to c-kit+Sca-1- increased 2 and 4 days after exposure to 5-fluorouracil (5-FU). These results are consistent with the relative enrichment of highly proliferative colony-forming cells by 5-FU. These data show that, although c-kit is found both on the primitive hematopoietic stem cells and progenitors, Sca-1+ cells are more primitive and respond better than Sca-1- cells to a combination of hematopoietic factors, including SCF and stromal cells."} {"id": "PMID:1281688", "title": "The human CD34 hematopoietic stem cell antigen promoter and a 3' enhancer direct hematopoietic expression in tissue culture.", "content": "The human CD34 hematopoietic stem cell antigen is a highly glycosylated type 1 membrane protein of unknown function. CD34 is expressed on 1% to 4% of bone marrow cells, including pluripotent stem cells and committed progenitors of each hematopoietic lineage. CD34 has also been shown to be expressed on the small vessel endothelium of a variety of tissues and on a subset of bone marrow stromal cells. We have chosen to use the human CD34 gene as model to examine the transcription factors and cis-elements required for stem cell/progenitor cell-specific gene regulation. We show here that the CD34 gene is transcriptionally regulated in tissue culture cells. Using a luciferase reporter gene, we have isolated and characterized an active CD34 promoter. A CD34-luciferase construct, containing 4.5 kb of 5' flanking DNA from a CD34 genomic clone, was 30-fold more active in CD34+ tissue culture cells than in HeLa cells. Sequences from the 3' end of the CD34 gene were shown to have enhancing activity in CD34+ T-lymphoblastic RPMI-8402 cells and not in CD34- U937 cells or in nonhematopoietic HeLa cells. We also show that a cytidine-guanosine island in the 5' end of the CD34 gene is heavily methylated in two CD34- hematopoietic cell lines and demethylated in two CD34+ cell lines. Analysis of the CD34 promoter should result in the identification of stem cell/progenitor cell-specific transcription factors and should provide a means to direct the expression of heterologous genes in hematopoietic stem cells and progenitors.", "contents": "The human CD34 hematopoietic stem cell antigen promoter and a 3' enhancer direct hematopoietic expression in tissue culture. The human CD34 hematopoietic stem cell antigen is a highly glycosylated type 1 membrane protein of unknown function. CD34 is expressed on 1% to 4% of bone marrow cells, including pluripotent stem cells and committed progenitors of each hematopoietic lineage. CD34 has also been shown to be expressed on the small vessel endothelium of a variety of tissues and on a subset of bone marrow stromal cells. We have chosen to use the human CD34 gene as model to examine the transcription factors and cis-elements required for stem cell/progenitor cell-specific gene regulation. We show here that the CD34 gene is transcriptionally regulated in tissue culture cells. Using a luciferase reporter gene, we have isolated and characterized an active CD34 promoter. A CD34-luciferase construct, containing 4.5 kb of 5' flanking DNA from a CD34 genomic clone, was 30-fold more active in CD34+ tissue culture cells than in HeLa cells. Sequences from the 3' end of the CD34 gene were shown to have enhancing activity in CD34+ T-lymphoblastic RPMI-8402 cells and not in CD34- U937 cells or in nonhematopoietic HeLa cells. We also show that a cytidine-guanosine island in the 5' end of the CD34 gene is heavily methylated in two CD34- hematopoietic cell lines and demethylated in two CD34+ cell lines. Analysis of the CD34 promoter should result in the identification of stem cell/progenitor cell-specific transcription factors and should provide a means to direct the expression of heterologous genes in hematopoietic stem cells and progenitors."} {"id": "PMID:1281689", "title": "Over-expression of c-src or v-src in bone marrow stromal cells stimulates hematopoiesis in long-term bone marrow culture.", "content": "The S17 murine stromal cell line was infected with retroviral vectors encoding the v-src and c-src oncogenes and cells expressing high levels of either pp60v-src or pp60c-src were isolated. Long-term bone marrow cultures (LTBMCs) established with these different stromal cell lines showed that progenitor cells proliferated to a greater extent in cultures with stromal cells that over-expressed either c-src or v-src. An increase in the number of granulocytes, monocytes, and colony-forming units granulocyte-macrophage (CFU-GM) in the nonadherent cell population of LTBMCs prepared with S17/v-src or S17/c-src stromal cells was observed. Conditioned media from the S17/v-src and S17/src stromal cell lines stimulated the formation of CFU-GM in the absence of additional hematopoietic cell growth factors. Conditioned media from S17/v-src and S17/c-src stimulated proliferation of the granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive cell line FDCP-1 and this stimulation was inhibited by neutralizing antisera to murine GM-CSF. An increase in the concentration of GM-CSF was confirmed by enzyme-linked immunosorbent assay. No secretion of interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor-alpha was detected by any of the stromal cell lines. There was no increase in the secretion of either CSF-1 or IL-6 by either S17/v-src or S17/c-src. The addition of 1 micrograms/mL monoclonal anti-GM-CSF antibody to LTBMCs caused a decrease in the number of nonadherent cells in cultures established with each of the different stromal cell lines. Northern blot analysis showed no difference in the level of GM-CSF RNA among the different stromal cell lines. These studies suggest that the increased proliferation of hematopoietic progenitor cells in LTBMCs with S17/v-src or S17/c-src cells may result from a posttranscriptional event that elevates production of GM-CSF by the S17/c-src and S17/v-src stromal cells.", "contents": "Over-expression of c-src or v-src in bone marrow stromal cells stimulates hematopoiesis in long-term bone marrow culture. The S17 murine stromal cell line was infected with retroviral vectors encoding the v-src and c-src oncogenes and cells expressing high levels of either pp60v-src or pp60c-src were isolated. Long-term bone marrow cultures (LTBMCs) established with these different stromal cell lines showed that progenitor cells proliferated to a greater extent in cultures with stromal cells that over-expressed either c-src or v-src. An increase in the number of granulocytes, monocytes, and colony-forming units granulocyte-macrophage (CFU-GM) in the nonadherent cell population of LTBMCs prepared with S17/v-src or S17/c-src stromal cells was observed. Conditioned media from the S17/v-src and S17/src stromal cell lines stimulated the formation of CFU-GM in the absence of additional hematopoietic cell growth factors. Conditioned media from S17/v-src and S17/c-src stimulated proliferation of the granulocyte-macrophage colony-stimulating factor (GM-CSF)-responsive cell line FDCP-1 and this stimulation was inhibited by neutralizing antisera to murine GM-CSF. An increase in the concentration of GM-CSF was confirmed by enzyme-linked immunosorbent assay. No secretion of interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor-alpha was detected by any of the stromal cell lines. There was no increase in the secretion of either CSF-1 or IL-6 by either S17/v-src or S17/c-src. The addition of 1 micrograms/mL monoclonal anti-GM-CSF antibody to LTBMCs caused a decrease in the number of nonadherent cells in cultures established with each of the different stromal cell lines. Northern blot analysis showed no difference in the level of GM-CSF RNA among the different stromal cell lines. These studies suggest that the increased proliferation of hematopoietic progenitor cells in LTBMCs with S17/v-src or S17/c-src cells may result from a posttranscriptional event that elevates production of GM-CSF by the S17/c-src and S17/v-src stromal cells."} {"id": "PMID:1281690", "title": "Expression and downregulation of cytotoxic cell protease 1 or Granzyme 'B' transcripts during myeloid differentiation of interleukin-3-dependent murine stem cell lines.", "content": "Using the technique of differential cDNA library screening, we have molecularly cloned a gene that is highly expressed in an undifferentiated myeloid multipotent and growth factor-dependent stem cell line (FDCP-Mix) and that downregulates as these cells are induced to differentiate along monocytic, granulocytic, and erythroid cell lineages. Sequence analysis of this gene has shown homology with a previously cloned gene, cytotoxic cell protease 1 (CCP1 or Granzyme 'B'), that has been shown to be expressed only in thymocytes, activated T cells, a mast cell line, and peritoneal exudate leukocytes. In situ hybridization, Northern blot analysis, and nuclear run-off assay has confirmed that expression of CCP1 is restricted to the phenotypically primitive multipotent undifferentiated. FDCP-Mix cells that are undergoing self-renewal in the presence of growth factors such as interleukin-3.", "contents": "Expression and downregulation of cytotoxic cell protease 1 or Granzyme 'B' transcripts during myeloid differentiation of interleukin-3-dependent murine stem cell lines. Using the technique of differential cDNA library screening, we have molecularly cloned a gene that is highly expressed in an undifferentiated myeloid multipotent and growth factor-dependent stem cell line (FDCP-Mix) and that downregulates as these cells are induced to differentiate along monocytic, granulocytic, and erythroid cell lineages. Sequence analysis of this gene has shown homology with a previously cloned gene, cytotoxic cell protease 1 (CCP1 or Granzyme 'B'), that has been shown to be expressed only in thymocytes, activated T cells, a mast cell line, and peritoneal exudate leukocytes. In situ hybridization, Northern blot analysis, and nuclear run-off assay has confirmed that expression of CCP1 is restricted to the phenotypically primitive multipotent undifferentiated. FDCP-Mix cells that are undergoing self-renewal in the presence of growth factors such as interleukin-3."} {"id": "PMID:1281691", "title": "Transfer and expression of the human multidrug resistance gene in mouse erythroleukemia cells.", "content": "Gene therapy in humans requires the transplantation of genetically modified cells, and it is important to select only those cells capable of expressing high levels of protein from the transferred gene. Expression of the human multiple drug resistance (MDR) gene confers resistance to a variety of compounds in vitro and in vivo. To determine the feasibility of conferring recipient erythroid cells with the MDR phenotype, we have transduced mouse erythroleukemia cells (MELC) with the MDR gene in a retroviral vector. We show here that MELC clones resistant to exposure to colchicine (an MDR-responsive agent) can be isolated, and demonstrate high levels of MDR RNA and protein expression. Increasing doses of colchicine increase the level of MDR RNA and protein expression significantly. These results indicate that it is possible to transfer and express the human MDR phenotype in mouse erythroid cells by retrovirally mediated gene transfer, and that drug selection can be used to enrich or purify populations of cells containing and expressing this gene.", "contents": "Transfer and expression of the human multidrug resistance gene in mouse erythroleukemia cells. Gene therapy in humans requires the transplantation of genetically modified cells, and it is important to select only those cells capable of expressing high levels of protein from the transferred gene. Expression of the human multiple drug resistance (MDR) gene confers resistance to a variety of compounds in vitro and in vivo. To determine the feasibility of conferring recipient erythroid cells with the MDR phenotype, we have transduced mouse erythroleukemia cells (MELC) with the MDR gene in a retroviral vector. We show here that MELC clones resistant to exposure to colchicine (an MDR-responsive agent) can be isolated, and demonstrate high levels of MDR RNA and protein expression. Increasing doses of colchicine increase the level of MDR RNA and protein expression significantly. These results indicate that it is possible to transfer and express the human MDR phenotype in mouse erythroid cells by retrovirally mediated gene transfer, and that drug selection can be used to enrich or purify populations of cells containing and expressing this gene."} {"id": "PMID:1281692", "title": "Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors.", "content": "Recent studies performed in the laboratory have established that interleukin-4 (IL-4) used in combination with anti-CD40 monoclonal antibody (MoAb) 89 presented on Ltk- mouse fibroblasts stably expressing human Fc gamma RII/CDw32 (referred to as the CD40 system) sustains long-term proliferation of normal human B cells. In the present study, B-cell chronic lymphocytic leukemias (B-CLLs) activated through slgs or CD40 were examined for their capacity to proliferate and differentiate in response to various cytokines. Our results indicate that the outcome of IL-4 stimulation on the in vitro growth of B-CLL depends on the signalling pathway used for their activation. Whereas IL-4 did not display any growth-stimulatory effect on B-CLL activated by Ig cross-linking agents, it could stimulate DNA synthesis and enhance the viable cell recovery when leukemic B cells were cultured in the CD40 system. Most B-CLL samples were induced for IgM synthesis upon Staphylococcus aureus strain Cowan I stimulation. This Ig response was potentiated by IL-2 and antagonized by IL-4. Anti-CD40 MoAb used alone or in combination with cytokines (IL-1 alpha to IL-6, interferon gamma, tumor necrosis factor gamma, and transforming growth factor beta) failed to induce Ig secretion from B-CLL cells. No evidence for Ig isotype switching was obtained with the cytokines listed above, regardless of the mode of activation. Taken together, our results suggest that B-CLL cells can be partially released from their apparent maturation block by IL-2 and Ig cross-linking agents. In contrast, combinations of IL-4 and cross-linked anti-CD40 antibodies induced entry of B-CLL cell into cycle, but poorly stimulated their differentiation into Ig secreting cells.", "contents": "Responsiveness of chronic lymphocytic leukemia B cells activated via surface Igs or CD40 to B-cell tropic factors. Recent studies performed in the laboratory have established that interleukin-4 (IL-4) used in combination with anti-CD40 monoclonal antibody (MoAb) 89 presented on Ltk- mouse fibroblasts stably expressing human Fc gamma RII/CDw32 (referred to as the CD40 system) sustains long-term proliferation of normal human B cells. In the present study, B-cell chronic lymphocytic leukemias (B-CLLs) activated through slgs or CD40 were examined for their capacity to proliferate and differentiate in response to various cytokines. Our results indicate that the outcome of IL-4 stimulation on the in vitro growth of B-CLL depends on the signalling pathway used for their activation. Whereas IL-4 did not display any growth-stimulatory effect on B-CLL activated by Ig cross-linking agents, it could stimulate DNA synthesis and enhance the viable cell recovery when leukemic B cells were cultured in the CD40 system. Most B-CLL samples were induced for IgM synthesis upon Staphylococcus aureus strain Cowan I stimulation. This Ig response was potentiated by IL-2 and antagonized by IL-4. Anti-CD40 MoAb used alone or in combination with cytokines (IL-1 alpha to IL-6, interferon gamma, tumor necrosis factor gamma, and transforming growth factor beta) failed to induce Ig secretion from B-CLL cells. No evidence for Ig isotype switching was obtained with the cytokines listed above, regardless of the mode of activation. Taken together, our results suggest that B-CLL cells can be partially released from their apparent maturation block by IL-2 and Ig cross-linking agents. In contrast, combinations of IL-4 and cross-linked anti-CD40 antibodies induced entry of B-CLL cell into cycle, but poorly stimulated their differentiation into Ig secreting cells."} {"id": "PMID:1281693", "title": "Rhom-2 expression does not always correlate with abnormalities on chromosome 11 at band p13 in T-cell acute lymphoblastic leukemia.", "content": "A frequent site for nonrandom recombination in T-cell acute lymphoblastic leukemia (T-ALL) is chromosome 11 at p13. The molecular characterization of a (7;11)(q35;p13) translocation showed that the translocation breakpoint was 2 kb 5' to the T-ALLbcr locus resulting in the juxtaposition of the T-cell receptor (TCR) beta gene to the rhom-2 gene locus. Northern blot analysis did not detect expression of the rhom-2 gene in the leukemic blasts of the (7;11) translocation. However, using a sensitive polymerase chain reaction (PCR)-based assay, the (7;11) translocation showed a trace expression of rhom-2 at a level of 0.01% of TCR-beta message. Because rhom-2 is considered a proto-oncogene, the significance of the trace expression of rhom-2 in the (7;11) translocation was investigated by comparing the level of rhom-2 expression in 7 additional T-ALLs, normal thymocytes, and CEM (pre-T) and HPB (mature-T) cell lines using the PCR assay. The CEM cells, normal thymocytes, and one patient, whose blasts had no cytogenetic abnormality of chromosome 11, did not express rhom-2 indicating that rhom-2 is not normally expressed in T cells. The other six T-ALLs fell into three categories: (1) two T-ALLs overexpressed rhom-2 in the presence of a translocation; (2) two T-ALLs had trace expression in the presence of a translocation; and (3) two T-ALLs had trace expression with no observable abnormalities on chromosome 11 at p13. Therefore, the data indicate that not all translocations at the T-ALLbcr locus result in overexpression of rhom-2. To account for the sharp contrast in rhom-2 expression seen in these T-ALLs, a model is proposed with a negative regulatory element in the T-ALLbcr locus that is disrupted in some of the cases leading to overexpression of rhom-2.", "contents": "Rhom-2 expression does not always correlate with abnormalities on chromosome 11 at band p13 in T-cell acute lymphoblastic leukemia. A frequent site for nonrandom recombination in T-cell acute lymphoblastic leukemia (T-ALL) is chromosome 11 at p13. The molecular characterization of a (7;11)(q35;p13) translocation showed that the translocation breakpoint was 2 kb 5' to the T-ALLbcr locus resulting in the juxtaposition of the T-cell receptor (TCR) beta gene to the rhom-2 gene locus. Northern blot analysis did not detect expression of the rhom-2 gene in the leukemic blasts of the (7;11) translocation. However, using a sensitive polymerase chain reaction (PCR)-based assay, the (7;11) translocation showed a trace expression of rhom-2 at a level of 0.01% of TCR-beta message. Because rhom-2 is considered a proto-oncogene, the significance of the trace expression of rhom-2 in the (7;11) translocation was investigated by comparing the level of rhom-2 expression in 7 additional T-ALLs, normal thymocytes, and CEM (pre-T) and HPB (mature-T) cell lines using the PCR assay. The CEM cells, normal thymocytes, and one patient, whose blasts had no cytogenetic abnormality of chromosome 11, did not express rhom-2 indicating that rhom-2 is not normally expressed in T cells. The other six T-ALLs fell into three categories: (1) two T-ALLs overexpressed rhom-2 in the presence of a translocation; (2) two T-ALLs had trace expression in the presence of a translocation; and (3) two T-ALLs had trace expression with no observable abnormalities on chromosome 11 at p13. Therefore, the data indicate that not all translocations at the T-ALLbcr locus result in overexpression of rhom-2. To account for the sharp contrast in rhom-2 expression seen in these T-ALLs, a model is proposed with a negative regulatory element in the T-ALLbcr locus that is disrupted in some of the cases leading to overexpression of rhom-2."} {"id": "PMID:1281694", "title": "Sensorimotor polyneuropathy and monoclonal IgM: a review of clinical and immunological features.", "content": "Main clinical and biological features of peripheral neuropathies associated with monoclonal IgM are reviewed. Special emphasis is given to the structure of these monoclonal auto-antibodies which points to an antigen (or some other kind of selective pressure) driven process.", "contents": "Sensorimotor polyneuropathy and monoclonal IgM: a review of clinical and immunological features. Main clinical and biological features of peripheral neuropathies associated with monoclonal IgM are reviewed. Special emphasis is given to the structure of these monoclonal auto-antibodies which points to an antigen (or some other kind of selective pressure) driven process."} {"id": "PMID:1281695", "title": "Kinetic energy measurements of molecular ions ejected into an electric field by matrix-assisted laser desorption.", "content": "Measurements of kinetic energy distributions of molecular ions ejected into an extraction field by matrix-assisted laser desorption are reported. The measurements were made in a time-of-flight mass spectrometer with an electrostatic mirror by measuring the reflected signal as a function of the difference between the accelerating voltage and the voltage applied to the mirror. The molecular ions were found to have less kinetic energy than the extraction field alone would normally provide, i.e., we observed an energy deficit. Under conditions typical for a matrix-assisted laser desorption experiment, the deficit is about 24 eV for molecular ions of insulin. The size of the deficit increases with the intensity of the molecular ion signal, and the molecular weight of the protein; it is also larger for negative molecular ions than for positive molecular ions.", "contents": "Kinetic energy measurements of molecular ions ejected into an electric field by matrix-assisted laser desorption. Measurements of kinetic energy distributions of molecular ions ejected into an extraction field by matrix-assisted laser desorption are reported. The measurements were made in a time-of-flight mass spectrometer with an electrostatic mirror by measuring the reflected signal as a function of the difference between the accelerating voltage and the voltage applied to the mirror. The molecular ions were found to have less kinetic energy than the extraction field alone would normally provide, i.e., we observed an energy deficit. Under conditions typical for a matrix-assisted laser desorption experiment, the deficit is about 24 eV for molecular ions of insulin. The size of the deficit increases with the intensity of the molecular ion signal, and the molecular weight of the protein; it is also larger for negative molecular ions than for positive molecular ions."} {"id": "PMID:1281696", "title": "Notochord of chick embryos secretes short-form type IX collagen prior to the onset of vertebral chondrogenesis.", "content": "The notochord of embryonic chicks produces type IX collagen, as well as type II collagen, prior to the onset of vertebral chondrogenesis. To address the question of whether the notochord secretes the \"long-form\" type IX collagen found in cartilage or the \"short-form\" type IX found in the cornea and vitreous humor, we examined immunoreactivity of the notochordal type IX collagen using two different monoclonal antibodies. The antibody 2C2 recognizes an epitope close to the carboxyl-terminus of the HMW fragment, which is present in both the long- and short-form type IX collagens, whereas another antibody 4D6 recognizes an epitope in the NC4 domain of the long-form type IX collagen, which is absent in the short-form type IX collagen. Therefore, the long-form is recognized by its reaction with both 2C2 and 4D6, while the short-form by its reaction with only 2C2 and no reaction with 4D6. Immunostaining of vertebral sections with 2C2 shows an identical distribution of staining with that for type II collagen, although the staining with 2C2 is less intense. The 2C2-reactive type IX collagen is found within the notochord at stage 14 and in the notochordal sheath at stage 20. Deposition of this collagen in the perinotochordal matrix increases with time and reaches a level comparable with that for type II at stage 31. In contrast, the 4D6-reactive type IX collagen is not found within the notochord nor in the notochordal sheath.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Notochord of chick embryos secretes short-form type IX collagen prior to the onset of vertebral chondrogenesis. The notochord of embryonic chicks produces type IX collagen, as well as type II collagen, prior to the onset of vertebral chondrogenesis. To address the question of whether the notochord secretes the \"long-form\" type IX collagen found in cartilage or the \"short-form\" type IX found in the cornea and vitreous humor, we examined immunoreactivity of the notochordal type IX collagen using two different monoclonal antibodies. The antibody 2C2 recognizes an epitope close to the carboxyl-terminus of the HMW fragment, which is present in both the long- and short-form type IX collagens, whereas another antibody 4D6 recognizes an epitope in the NC4 domain of the long-form type IX collagen, which is absent in the short-form type IX collagen. Therefore, the long-form is recognized by its reaction with both 2C2 and 4D6, while the short-form by its reaction with only 2C2 and no reaction with 4D6. Immunostaining of vertebral sections with 2C2 shows an identical distribution of staining with that for type II collagen, although the staining with 2C2 is less intense. The 2C2-reactive type IX collagen is found within the notochord at stage 14 and in the notochordal sheath at stage 20. Deposition of this collagen in the perinotochordal matrix increases with time and reaches a level comparable with that for type II at stage 31. In contrast, the 4D6-reactive type IX collagen is not found within the notochord nor in the notochordal sheath.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281697", "title": "Development of olfactory nerve glia defined by a monoclonal antibody specific for Schwann cells.", "content": "Although there is considerable interest in the possible role of olfactory glia in the pathfinding abilities of olfactory nerve axons, the complete development of these glia in vivo has not been described. Using a specific Schwann cell marker, the 1E8 antibody, we have found that olfactory nerve glia can be identified throughout development. These glia appear to originate in the olfactory placode and migrate initially into the periphery of the olfactory nerve, and later into the center of the nerve. Olfactory nerve glia enter the presumptive olfactory bulb with the olfactory receptor neuron axons and distribute themselves along the edge of the olfactory nerve layer. The fact that olfactory nerve glia are specifically immunostained by the 1E8 monoclonal antibody, which recognizes the Schwann cell-specific protein P0, suggests that these cells more closely resemble Schwann cells than astrocytes or enteric glia. These results support and extend previous findings suggesting that olfactory nerve glia have distinctive developmental and anatomical features which may be important to the regenerative capacity of the olfactory system.", "contents": "Development of olfactory nerve glia defined by a monoclonal antibody specific for Schwann cells. Although there is considerable interest in the possible role of olfactory glia in the pathfinding abilities of olfactory nerve axons, the complete development of these glia in vivo has not been described. Using a specific Schwann cell marker, the 1E8 antibody, we have found that olfactory nerve glia can be identified throughout development. These glia appear to originate in the olfactory placode and migrate initially into the periphery of the olfactory nerve, and later into the center of the nerve. Olfactory nerve glia enter the presumptive olfactory bulb with the olfactory receptor neuron axons and distribute themselves along the edge of the olfactory nerve layer. The fact that olfactory nerve glia are specifically immunostained by the 1E8 monoclonal antibody, which recognizes the Schwann cell-specific protein P0, suggests that these cells more closely resemble Schwann cells than astrocytes or enteric glia. These results support and extend previous findings suggesting that olfactory nerve glia have distinctive developmental and anatomical features which may be important to the regenerative capacity of the olfactory system."} {"id": "PMID:1281698", "title": "[Brain metastasis of choriocarcinoma in males. Apropos of a case. Review of the literature].", "content": "A 22 year-old male patient had a choriocarcinoma of the mediastinum metastatic to the brain, liver, lung and skin. He was treated with five cycles of chemotherapy containing cisplatinum, vinblastine, VP16 and bleomycin and he achieved a partial remission. Then he developed a progressive disease exclusively located to the brain and he died of an intracranial hemorrhage. The autopsy showed the mediastinum and the lung being free of residual trophoblastic tumor. Pure choriocarcinoma is rare in males, but brain metastases are frequently present in this case. Therapeutic guidelines are uncertain, so they must refer to the experience obtained in gestational choriocarcinoma. Two groups of patients are individualized both in male germ cell tumors and in placental choriocarcinoma: one group of patients with brain metastases at diagnosis, with a better prognosis, and one group of patients with brain metastases occurring in the course of the disease, with a poor outcome. The risk of intratumoral hemorrhage is common to all varieties of choriocarcinoma brain metastases and is not lowered by greater effectiveness of the chemotherapy. Brain metastases found at the moment of the choriocarcinoma diagnosis require chemotherapy and radiotherapy and in some selected cases, a surgical removal.", "contents": "[Brain metastasis of choriocarcinoma in males. Apropos of a case. Review of the literature]. A 22 year-old male patient had a choriocarcinoma of the mediastinum metastatic to the brain, liver, lung and skin. He was treated with five cycles of chemotherapy containing cisplatinum, vinblastine, VP16 and bleomycin and he achieved a partial remission. Then he developed a progressive disease exclusively located to the brain and he died of an intracranial hemorrhage. The autopsy showed the mediastinum and the lung being free of residual trophoblastic tumor. Pure choriocarcinoma is rare in males, but brain metastases are frequently present in this case. Therapeutic guidelines are uncertain, so they must refer to the experience obtained in gestational choriocarcinoma. Two groups of patients are individualized both in male germ cell tumors and in placental choriocarcinoma: one group of patients with brain metastases at diagnosis, with a better prognosis, and one group of patients with brain metastases occurring in the course of the disease, with a poor outcome. The risk of intratumoral hemorrhage is common to all varieties of choriocarcinoma brain metastases and is not lowered by greater effectiveness of the chemotherapy. Brain metastases found at the moment of the choriocarcinoma diagnosis require chemotherapy and radiotherapy and in some selected cases, a surgical removal."} {"id": "PMID:1281699", "title": "Glucocorticoid treatment or food deprivation counteract the stimulating effect of growth hormone on rat cortical bone strength.", "content": "Growth hormone (GH) has been found to increase the length, thickness and bending strength of rat femora. The present study was designed to investigate if glucocorticoid treatment or food restriction would interfere with the effect of exogenous GH on bone growth. Male rats treated with GH for 30 days experienced a weight gain of 30-35% and longitudinal and periosteal femoral growth. A dose-related increase in the bending strength of the femora was found and was explained by an increased thickness of the femora. In spite of a reduced real density, biomechanical competence was preserved after GH treatment. GH treatment combined with a relatively small dose of glucocorticoid, which in itself had no significant effect on bone growth and strength, reduced the stimulating effect of GH on body weight gain, femoral growth and strength. GH-treated rats that were food restricted, so as to limit their body weight gain to that of the saline group, experienced significant longitudinal and periosteal femoral growth. Bone strength, however, was not increased, which conforms to a reduced mineralization and increased porosity of the femora. Young's modulus (normalized bone stiffness) was significantly decreased in this group, probably as a result of decreased mineralization. Furthermore, the combination of GH treatment and food restriction resulted in a reduced apparent density indicating increased bone resorption.", "contents": "Glucocorticoid treatment or food deprivation counteract the stimulating effect of growth hormone on rat cortical bone strength. Growth hormone (GH) has been found to increase the length, thickness and bending strength of rat femora. The present study was designed to investigate if glucocorticoid treatment or food restriction would interfere with the effect of exogenous GH on bone growth. Male rats treated with GH for 30 days experienced a weight gain of 30-35% and longitudinal and periosteal femoral growth. A dose-related increase in the bending strength of the femora was found and was explained by an increased thickness of the femora. In spite of a reduced real density, biomechanical competence was preserved after GH treatment. GH treatment combined with a relatively small dose of glucocorticoid, which in itself had no significant effect on bone growth and strength, reduced the stimulating effect of GH on body weight gain, femoral growth and strength. GH-treated rats that were food restricted, so as to limit their body weight gain to that of the saline group, experienced significant longitudinal and periosteal femoral growth. Bone strength, however, was not increased, which conforms to a reduced mineralization and increased porosity of the femora. Young's modulus (normalized bone stiffness) was significantly decreased in this group, probably as a result of decreased mineralization. Furthermore, the combination of GH treatment and food restriction resulted in a reduced apparent density indicating increased bone resorption."} {"id": "PMID:1281700", "title": "Expression of antisense or sense RNA of an ankyrin repeat-containing gene blocks chloroplast differentiation in arabidopsis.", "content": "The Arabidopsis AKR gene that encodes a protein with four ankyrin repeats (a 33-amino acid motif that appears in the 89K domain of the human protein ankyrin) was isolated and characterized. A short sequence outside the ankyrin repeats is similar to that of the protein of the Drosophila muscle segment homeobox (msh) gene. The expression of the AKR gene is light dependent, and transgenic Arabidopsis plants with two or more copies of an antisense or sense AKR construct became chlorotic in a developmentally regulated manner. The chlorotic phenotype was genetically transmitted to the next generation, although most chlorotic plants produced much less seed. Reduced presence of thylakoid membranes and loss of grana are found in the plastids of chlorotic leaves, indicating that antisense or sense AKR has blocked chloroplast differentiation. This study indicates the importance of ankyrin repeat-containing proteins, not only in yeast and animals, but in plants as well.", "contents": "Expression of antisense or sense RNA of an ankyrin repeat-containing gene blocks chloroplast differentiation in arabidopsis. The Arabidopsis AKR gene that encodes a protein with four ankyrin repeats (a 33-amino acid motif that appears in the 89K domain of the human protein ankyrin) was isolated and characterized. A short sequence outside the ankyrin repeats is similar to that of the protein of the Drosophila muscle segment homeobox (msh) gene. The expression of the AKR gene is light dependent, and transgenic Arabidopsis plants with two or more copies of an antisense or sense AKR construct became chlorotic in a developmentally regulated manner. The chlorotic phenotype was genetically transmitted to the next generation, although most chlorotic plants produced much less seed. Reduced presence of thylakoid membranes and loss of grana are found in the plastids of chlorotic leaves, indicating that antisense or sense AKR has blocked chloroplast differentiation. This study indicates the importance of ankyrin repeat-containing proteins, not only in yeast and animals, but in plants as well."} {"id": "PMID:1281701", "title": "[Structural and neurochemical characteristics of sex-dependent neurons of the brain transplanted to the anterior chamber of the eye].", "content": "Histological, electron microscopic and histoautoradiographic methods were used to study structural and neurochemical features of the development of neurons of the hypothalamic paraventricular nuclei (PVN) and the medullary nucleus of the solitary tract (NST), which had been grafted from 20-day-old rat fetuses into the anterior eye chamber of ovariectomized female rats not exposed (control group) and exposed (experimental group) to prolonged estrogen action (during 4 weeks). The exposure to estrogen stimulated the growth, cell differentiation, RNA transcription and synaptogenesis in the grafted PVN and NST neurons. The data obtained seem to provide additional evidence that PVN and NST neurons belong to sex-dependent brain neurons.", "contents": "[Structural and neurochemical characteristics of sex-dependent neurons of the brain transplanted to the anterior chamber of the eye]. Histological, electron microscopic and histoautoradiographic methods were used to study structural and neurochemical features of the development of neurons of the hypothalamic paraventricular nuclei (PVN) and the medullary nucleus of the solitary tract (NST), which had been grafted from 20-day-old rat fetuses into the anterior eye chamber of ovariectomized female rats not exposed (control group) and exposed (experimental group) to prolonged estrogen action (during 4 weeks). The exposure to estrogen stimulated the growth, cell differentiation, RNA transcription and synaptogenesis in the grafted PVN and NST neurons. The data obtained seem to provide additional evidence that PVN and NST neurons belong to sex-dependent brain neurons."} {"id": "PMID:1281704", "title": "[Monoamines in the hypothalamic structures in the first few hours after immunization].", "content": "This paper examines the time course of changes in the levels of dopamine, norepinephrine, serotonin and their metabolites in the hypothalamic structures closely related to neurohumoral regulation of immunogenesis. The findings suggest that the monoaminergic systems of the brain are widely involved in the body's response to antigen, which may lead to the conclusion that there are numerous modes of entering information from the immune to the nervous system.", "contents": "[Monoamines in the hypothalamic structures in the first few hours after immunization]. This paper examines the time course of changes in the levels of dopamine, norepinephrine, serotonin and their metabolites in the hypothalamic structures closely related to neurohumoral regulation of immunogenesis. The findings suggest that the monoaminergic systems of the brain are widely involved in the body's response to antigen, which may lead to the conclusion that there are numerous modes of entering information from the immune to the nervous system."} {"id": "PMID:1281705", "title": "[Problem of chemical structural specificity of the brain].", "content": "The structurally specific chemical factors (SSCF) are considered as are differentiation-, regeneration- and normal function-promoting factors of embryonic and adult brain tissue. From this point of view the authors' data concerning SSCF expression after brain lesion are discussed. Analysis is made of the importance of further studies into the identification of these factors and elucidation of the biological role they play in the compensatory processes after brain damage in order to develop new approaches to the treatment of brain diseases.", "contents": "[Problem of chemical structural specificity of the brain]. The structurally specific chemical factors (SSCF) are considered as are differentiation-, regeneration- and normal function-promoting factors of embryonic and adult brain tissue. From this point of view the authors' data concerning SSCF expression after brain lesion are discussed. Analysis is made of the importance of further studies into the identification of these factors and elucidation of the biological role they play in the compensatory processes after brain damage in order to develop new approaches to the treatment of brain diseases."} {"id": "PMID:1281711", "title": "[Physiologically active brain proteins as possible markers of mental diseases].", "content": "It has been shown that there is a decrease in the content and activity of three neurospecific proteins (neurospecific enolase--NSE, glial fibrillar acid protein--GFAP and creatine kinase CK BB) in various structures of the postmortal brain of schizophrenic patients and those with senile dementia and Alzheimer's disease. The differences in the intensity and localization of these disorders in the above patients' groups have been detected. A previously unknown component of a pathological process in the brain, indicated by the decrease of the CK content and activity has been discovered. It is suggested that the decrease of the content of CK BB results in the development of energy deficit in the brain in patients with mental disorders.", "contents": "[Physiologically active brain proteins as possible markers of mental diseases]. It has been shown that there is a decrease in the content and activity of three neurospecific proteins (neurospecific enolase--NSE, glial fibrillar acid protein--GFAP and creatine kinase CK BB) in various structures of the postmortal brain of schizophrenic patients and those with senile dementia and Alzheimer's disease. The differences in the intensity and localization of these disorders in the above patients' groups have been detected. A previously unknown component of a pathological process in the brain, indicated by the decrease of the CK content and activity has been discovered. It is suggested that the decrease of the content of CK BB results in the development of energy deficit in the brain in patients with mental disorders."} {"id": "PMID:1281712", "title": "[Tachykinins in the central mechanisms of biological motivation].", "content": "The studies have indicated that tachykinin peptides are selectively involved in the central mechanisms of biological motivations. The injections of tachykinins suppress food motivation, salt appetite, to a lesser extent modifying defensive behaviour. Neuropeptides, including tachykinins, affect the prompt induction of early genes, which in turn enables a neuron to transform a short-term synaptic stimulation to long-term changes of synaptic sensitivity.", "contents": "[Tachykinins in the central mechanisms of biological motivation]. The studies have indicated that tachykinin peptides are selectively involved in the central mechanisms of biological motivations. The injections of tachykinins suppress food motivation, salt appetite, to a lesser extent modifying defensive behaviour. Neuropeptides, including tachykinins, affect the prompt induction of early genes, which in turn enables a neuron to transform a short-term synaptic stimulation to long-term changes of synaptic sensitivity."} {"id": "PMID:1281713", "title": "[Search for the substances selectively acting on the mediatory transmission of stimulatory amino acids].", "content": "The design of new compounds selectively acting on excitatory amino acid neurotransmission is discussed on the basis of structure-activity relationships. Some new compounds, derivatives of aspartic, glutamic, 2,3-diaminopropionic and some other acids, are cited as examples.", "contents": "[Search for the substances selectively acting on the mediatory transmission of stimulatory amino acids]. The design of new compounds selectively acting on excitatory amino acid neurotransmission is discussed on the basis of structure-activity relationships. Some new compounds, derivatives of aspartic, glutamic, 2,3-diaminopropionic and some other acids, are cited as examples."} {"id": "PMID:1281715", "title": "Adolescent pregnancy and early intervention programs benefit from case management.", "content": "Case Management methods are being adapted to effectively serve two vulnerable populations: pregnant and parenting adolescents, and infants and toddlers with disabilities of developmental delay and their families. This article describes the case management model developed by California's Adolescent Family Life program and discusses issues related to providing family-centered, community-based case management in early intervention programs.", "contents": "Adolescent pregnancy and early intervention programs benefit from case management. Case Management methods are being adapted to effectively serve two vulnerable populations: pregnant and parenting adolescents, and infants and toddlers with disabilities of developmental delay and their families. This article describes the case management model developed by California's Adolescent Family Life program and discusses issues related to providing family-centered, community-based case management in early intervention programs."} {"id": "PMID:1281716", "title": "Potentiation of the vasorelaxant activity of nitric oxide by hydroxyguanidine: implications for the nature of endothelium-derived relaxing factor.", "content": "1. We recently demonstrated that NG-hydroxy-L-arginine (L-HOArg) is a substrate for the constitutive nitric oxide (NO) synthase present in bovine aortic endothelial cells cultured on microcarrier beads (EC). Furthermore, L-HOArg reacts chemically with NO released from these cells to form a potent and more stable vasodilator. This is most likely through a reaction with the hydroxyguanidino group. 2. Here, we studied the interaction of a simpler molecule, hydroxyguanidine (HOG) with NO. 3. HOG (10 microM), like L-HOArg (10 microM) or NG-hydroxy-D-arginine (D-HOArg, 10 microM), potentiated and stabilized the relaxant activity of authentic NO. 4. When NO was bubbled through the solution of HOG, a new compound was formed. It had similar physicochemical properties to those of the previously described L-HOArg/NO adduct. It was also a potent vasodilator and its action was inhibited by oxyhaemoglobin (10 microM), indicating formation of a NO-containing substance. 5. Moreover, HOG (10 microM) was not a substrate for the constitutive NO synthase present in the microsomal fraction of EC and did not affect the flow-induced or bradykinin-stimulated generation of prostacyclin, as measured by 6-keto-PGF1 alpha. 6. We also studied the effect of HOG on the endothelium-derived relaxing factor (EDRF) released from the column of EC. HOG (10 microM) potentiated and stabilized the relaxations of rabbit aortic strips induced by EDRF released by bradykinin (5-20 pmol) or ADP (5-10 nmol). These relaxations were inhibited by NG-nitro-L-arginine methyl ester (L-NAME, 10 microM) and L-arginine (L-Arg, 1 mM) reversed the inhibitory effects of L-NAME. 7. HOG (10 iM) augmented the basal (flow-induced) EC-dependent relaxations which were also inhibited by L-NAME (10 1M) and the effects of L-NOArg were reversed by L-Arg (1 mM).8. Thus, the hydroxyguanidino moiety of L-HOArg is involved in the reaction with NO. Moreover, the comparable reaction of the hydroxyguanidino compounds with NO on the one hand and with flowinduced and agonist-triggered EDRF on the other, strongly supports their common identity.", "contents": "Potentiation of the vasorelaxant activity of nitric oxide by hydroxyguanidine: implications for the nature of endothelium-derived relaxing factor. 1. We recently demonstrated that NG-hydroxy-L-arginine (L-HOArg) is a substrate for the constitutive nitric oxide (NO) synthase present in bovine aortic endothelial cells cultured on microcarrier beads (EC). Furthermore, L-HOArg reacts chemically with NO released from these cells to form a potent and more stable vasodilator. This is most likely through a reaction with the hydroxyguanidino group. 2. Here, we studied the interaction of a simpler molecule, hydroxyguanidine (HOG) with NO. 3. HOG (10 microM), like L-HOArg (10 microM) or NG-hydroxy-D-arginine (D-HOArg, 10 microM), potentiated and stabilized the relaxant activity of authentic NO. 4. When NO was bubbled through the solution of HOG, a new compound was formed. It had similar physicochemical properties to those of the previously described L-HOArg/NO adduct. It was also a potent vasodilator and its action was inhibited by oxyhaemoglobin (10 microM), indicating formation of a NO-containing substance. 5. Moreover, HOG (10 microM) was not a substrate for the constitutive NO synthase present in the microsomal fraction of EC and did not affect the flow-induced or bradykinin-stimulated generation of prostacyclin, as measured by 6-keto-PGF1 alpha. 6. We also studied the effect of HOG on the endothelium-derived relaxing factor (EDRF) released from the column of EC. HOG (10 microM) potentiated and stabilized the relaxations of rabbit aortic strips induced by EDRF released by bradykinin (5-20 pmol) or ADP (5-10 nmol). These relaxations were inhibited by NG-nitro-L-arginine methyl ester (L-NAME, 10 microM) and L-arginine (L-Arg, 1 mM) reversed the inhibitory effects of L-NAME. 7. HOG (10 iM) augmented the basal (flow-induced) EC-dependent relaxations which were also inhibited by L-NAME (10 1M) and the effects of L-NOArg were reversed by L-Arg (1 mM).8. Thus, the hydroxyguanidino moiety of L-HOArg is involved in the reaction with NO. Moreover, the comparable reaction of the hydroxyguanidino compounds with NO on the one hand and with flowinduced and agonist-triggered EDRF on the other, strongly supports their common identity."} {"id": "PMID:1281717", "title": "Pterins inhibit nitric oxide synthase activity in rat alveolar macrophages.", "content": "1. The synthesis of nitrite and citrulline from L-arginine by immune-stimulated rat alveolar macrophages and the modulation of this synthesis were studied. 2,4-Diamino-6-hydroxypyrimidine (DAHP), 6R-5,6,7,8-tetrahydro-L-biopterin (BH4) and L-sepiapterin were potent inhibitors of the recombinant interferon-gamma induced production of nitrogen oxides in intact cultured cells with I50 values for BH4 and L-sepiapterin of approximately 10 microM. They were equally effective in inhibiting the induced production of citrulline. This inhibitory effect was concentration-dependent for all three modulators investigated. 2. The inhibitory effects were not dependent on incubation times of either 24 or 48 h, on the immune-stimulus used (lipopolysaccharide, interferon-gamma), or whether these stimuli were added during or after the induction period. 3. Pterin-6-carboxylic acid (PCA), which cannot be converted into BH4, and methotrexate (MTX), which inhibits dihydrofolatereductase but not de novo biosynthesis of BH4, did not change the production of nitrite. 4. The data indicate that DAHP, an inhibitor of the de novo biosynthesis of the co-factor BH4, blocks the nitric oxide synthase activity in intact cells. Since the pterins BH4 and L-sepiapterin blocked the L-arginine dependent production of nitrite and citrulline, the activity of nitric oxide synthase in phagocytic cells may be regulated by metabolic endproducts of the de novo biosynthesis of BH4.", "contents": "Pterins inhibit nitric oxide synthase activity in rat alveolar macrophages. 1. The synthesis of nitrite and citrulline from L-arginine by immune-stimulated rat alveolar macrophages and the modulation of this synthesis were studied. 2,4-Diamino-6-hydroxypyrimidine (DAHP), 6R-5,6,7,8-tetrahydro-L-biopterin (BH4) and L-sepiapterin were potent inhibitors of the recombinant interferon-gamma induced production of nitrogen oxides in intact cultured cells with I50 values for BH4 and L-sepiapterin of approximately 10 microM. They were equally effective in inhibiting the induced production of citrulline. This inhibitory effect was concentration-dependent for all three modulators investigated. 2. The inhibitory effects were not dependent on incubation times of either 24 or 48 h, on the immune-stimulus used (lipopolysaccharide, interferon-gamma), or whether these stimuli were added during or after the induction period. 3. Pterin-6-carboxylic acid (PCA), which cannot be converted into BH4, and methotrexate (MTX), which inhibits dihydrofolatereductase but not de novo biosynthesis of BH4, did not change the production of nitrite. 4. The data indicate that DAHP, an inhibitor of the de novo biosynthesis of the co-factor BH4, blocks the nitric oxide synthase activity in intact cells. Since the pterins BH4 and L-sepiapterin blocked the L-arginine dependent production of nitrite and citrulline, the activity of nitric oxide synthase in phagocytic cells may be regulated by metabolic endproducts of the de novo biosynthesis of BH4."} {"id": "PMID:1281718", "title": "Inhibitors of nitric oxide synthase selectively reduce flow in tumor-associated neovasculature.", "content": "1. The effects of L-arginine analogues, NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA) and methylene blue on blood flow in a murine adenocarcinoma and melanoma have been investigated. 2. Sponge implants in Balb/c and C57/BL mice were used to host proliferating tumour cells while the washout of 133Xe was employed to assess local blood flow in the implanted sponges. 3. Pharmacological inhibition of nitric oxide (NO) reduced blood flow in both tumours but this effect was reversed by administration of L-arginine. 4. In marked contrast, the effect of these same NO inhibitors on the blood flow in sponge-induced non-neoplastic granulation tissue was negligible. 5. These results strongly suggest that: (a) flow in tumour vessels is modulated by nitric oxide which maintains a dilator tone in neoplastic tissue; (b) the constrictor activity (as monitored by an increase in t1/2 of 133Xe) of NO inhibitors may be attributed to the removal of such dilator tone; (c) many of the abnormalities described in tumour vasculature, such as hyporeactivity or unresponsiveness to vasoactive mediators and maximum vasodilation, may be due to an increase in NO synthesis in cancers.", "contents": "Inhibitors of nitric oxide synthase selectively reduce flow in tumor-associated neovasculature. 1. The effects of L-arginine analogues, NG-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA) and methylene blue on blood flow in a murine adenocarcinoma and melanoma have been investigated. 2. Sponge implants in Balb/c and C57/BL mice were used to host proliferating tumour cells while the washout of 133Xe was employed to assess local blood flow in the implanted sponges. 3. Pharmacological inhibition of nitric oxide (NO) reduced blood flow in both tumours but this effect was reversed by administration of L-arginine. 4. In marked contrast, the effect of these same NO inhibitors on the blood flow in sponge-induced non-neoplastic granulation tissue was negligible. 5. These results strongly suggest that: (a) flow in tumour vessels is modulated by nitric oxide which maintains a dilator tone in neoplastic tissue; (b) the constrictor activity (as monitored by an increase in t1/2 of 133Xe) of NO inhibitors may be attributed to the removal of such dilator tone; (c) many of the abnormalities described in tumour vasculature, such as hyporeactivity or unresponsiveness to vasoactive mediators and maximum vasodilation, may be due to an increase in NO synthesis in cancers."} {"id": "PMID:1281719", "title": "Protective effects of inhibitors of nitric oxide synthase in immune complex-induced vasculitis.", "content": "1. The ability of analogues of L-arginine (N-iminoethyl-L-ornithine (L-NIO), NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L-arginine (L-NNA)) to protect against inflammatory injury induced by activated neutrophils was investigated in rats following intradermal or intrapulmonary deposition of immune complexes. 2. The descending order of potency for protective effects of these analogues was: L-NIO > L-NMMA > L-NNA = L-NAME. The approximate IC50 value for L-NIO in the dermal vasculitis model was 65 microM. For all other compounds, the IC50 values were > 5 mM. 3. The protective effect of L-NIO in the skin was reversed in a dose-dependent manner by the presence of L-arginine, but not by D-arginine. L-Arginine also reversed the protective effects of L-NIO in immune complex-induced lung injury. 4. The protective effects of L-NIO were not associated with reductions in neutrophil accumulation, as measured by extraction from tissues of myeloperoxidase. 5. These data demonstrate that L-NIO has the most potent protective effects against immune complex-induced vascular injury induced by activated macrophages. Furthermore, they indicate that this injury is dependent upon the generation of nitric oxide.", "contents": "Protective effects of inhibitors of nitric oxide synthase in immune complex-induced vasculitis. 1. The ability of analogues of L-arginine (N-iminoethyl-L-ornithine (L-NIO), NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME) and NG-nitro-L-arginine (L-NNA)) to protect against inflammatory injury induced by activated neutrophils was investigated in rats following intradermal or intrapulmonary deposition of immune complexes. 2. The descending order of potency for protective effects of these analogues was: L-NIO > L-NMMA > L-NNA = L-NAME. The approximate IC50 value for L-NIO in the dermal vasculitis model was 65 microM. For all other compounds, the IC50 values were > 5 mM. 3. The protective effect of L-NIO in the skin was reversed in a dose-dependent manner by the presence of L-arginine, but not by D-arginine. L-Arginine also reversed the protective effects of L-NIO in immune complex-induced lung injury. 4. The protective effects of L-NIO were not associated with reductions in neutrophil accumulation, as measured by extraction from tissues of myeloperoxidase. 5. These data demonstrate that L-NIO has the most potent protective effects against immune complex-induced vascular injury induced by activated macrophages. Furthermore, they indicate that this injury is dependent upon the generation of nitric oxide."} {"id": "PMID:1281720", "title": "Inflammatory mechanisms in the passive cutaneous anaphylactic reaction in the rabbit: evidence that novel mediators are involved.", "content": "1. We have examined the mechanisms of local oedema formation in the passive cutaneous anaphylactic (PCA) reaction in the rabbit. 2. IgE-containing antiserum was injected i.d. and allowed to sensitize skin sites for periods up to 240 h. Antigen (bovine gamma globulin) was injected i.d. or i.v. and local oedema formation assessed by the accumulation of i.v. injected 125I-labelled rabbit serum albumin. Potential inhibitors were mixed with antigen prior to i.d. injection or were administered i.v. 3. Maximum oedema formation was observed when a sensitization period of 48-72 h was used. Oedema formation in the PCA reaction was of short duration with a t 1/2 of approximately 15 min. No evidence of late oedema formation (up to 6 h) was found. 4. Local oedema formation in the PCA was reduced by indomethacin suggesting that vasodilator, oedema-potentiating prostaglandins were released. However, it was likely that other vasodilators were also generated. 5. Antihistamines were poor inhibitors of oedema formation as were PAF antagonists, a 5-lipoxygenase inhibitor, a kallikrein inhibitor, a bradykinin antagonist and anti-C5a antibody. 6. Local oedema formation in the PCA was partially reduced by neutrophil depletion and colchicine suggesting that neutrophil-dependent mediators were involved. 7. Exudate fluid from anaphylactic reactions in the rabbit peritoneal cavity contained permeability-increasing activity when injected into rabbit skin. This activity is now being characterized. 8. A vasodilator prostaglandin appears to be released in the rabbit PCA reaction but none of the established permeability-increasing mediators appears to be involved. Thus, there may be novel inflammatory mediators generated in this reaction which may have relevance for human allergic skin diseases.", "contents": "Inflammatory mechanisms in the passive cutaneous anaphylactic reaction in the rabbit: evidence that novel mediators are involved. 1. We have examined the mechanisms of local oedema formation in the passive cutaneous anaphylactic (PCA) reaction in the rabbit. 2. IgE-containing antiserum was injected i.d. and allowed to sensitize skin sites for periods up to 240 h. Antigen (bovine gamma globulin) was injected i.d. or i.v. and local oedema formation assessed by the accumulation of i.v. injected 125I-labelled rabbit serum albumin. Potential inhibitors were mixed with antigen prior to i.d. injection or were administered i.v. 3. Maximum oedema formation was observed when a sensitization period of 48-72 h was used. Oedema formation in the PCA reaction was of short duration with a t 1/2 of approximately 15 min. No evidence of late oedema formation (up to 6 h) was found. 4. Local oedema formation in the PCA was reduced by indomethacin suggesting that vasodilator, oedema-potentiating prostaglandins were released. However, it was likely that other vasodilators were also generated. 5. Antihistamines were poor inhibitors of oedema formation as were PAF antagonists, a 5-lipoxygenase inhibitor, a kallikrein inhibitor, a bradykinin antagonist and anti-C5a antibody. 6. Local oedema formation in the PCA was partially reduced by neutrophil depletion and colchicine suggesting that neutrophil-dependent mediators were involved. 7. Exudate fluid from anaphylactic reactions in the rabbit peritoneal cavity contained permeability-increasing activity when injected into rabbit skin. This activity is now being characterized. 8. A vasodilator prostaglandin appears to be released in the rabbit PCA reaction but none of the established permeability-increasing mediators appears to be involved. Thus, there may be novel inflammatory mediators generated in this reaction which may have relevance for human allergic skin diseases."} {"id": "PMID:1281721", "title": "L-arginine dilates rat pial arterioles by nitric oxide-dependent mechanisms and increases blood flow during focal cerebral ischaemia.", "content": "L-Arginine (> or = 30 mg kg-1, i.v.), but not D-arginine (300 mg kg-1) administered 5 min after unilateral common carotid/middle cerebral artery occlusion increased regional cerebral blood flow (rCBF) within the dorsolateral ischaemic cortex in spontaneously hypertensive rats. L-Arginine (300 mg kg-1) increased rCBF from 22 +/- 2.7 to 33 +/- 4% of baseline as measured by laser-Doppler flowmetry. This increase may explain the ability of L-arginine to reduce infarct size following focal cerebral ischaemia, as reported previously. The mechanism appears to be mediated by nitric oxide since topical L-NAME (1 microM), a nitric oxide synthase inhibitor, decreased pial arteriole calibre from 115 +/- 2.2 to 106 +/- 0.9% of baseline following L-arginine infusion (300 mg kg-1).", "contents": "L-arginine dilates rat pial arterioles by nitric oxide-dependent mechanisms and increases blood flow during focal cerebral ischaemia. L-Arginine (> or = 30 mg kg-1, i.v.), but not D-arginine (300 mg kg-1) administered 5 min after unilateral common carotid/middle cerebral artery occlusion increased regional cerebral blood flow (rCBF) within the dorsolateral ischaemic cortex in spontaneously hypertensive rats. L-Arginine (300 mg kg-1) increased rCBF from 22 +/- 2.7 to 33 +/- 4% of baseline as measured by laser-Doppler flowmetry. This increase may explain the ability of L-arginine to reduce infarct size following focal cerebral ischaemia, as reported previously. The mechanism appears to be mediated by nitric oxide since topical L-NAME (1 microM), a nitric oxide synthase inhibitor, decreased pial arteriole calibre from 115 +/- 2.2 to 106 +/- 0.9% of baseline following L-arginine infusion (300 mg kg-1)."} {"id": "PMID:1281722", "title": "Protein kinase C-independent sensitization of contractile proteins to Ca2+ in alpha-toxin-permeabilized smooth muscle cells from the guinea-pig stomach.", "content": "Involvement of protein kinase C in receptor-operated Ca2+ sensitization of cell shortening was investigated by use of alpha-toxin-permeabilized smooth muscle cells from the fundus of the guinea-pig. Most of the isolated cells responded to 0.6 microM Ca2+ with a maximal shortening to approximately 65% of the resting cell length. Addition of acetylcholine (ACh) at a maximal concentration (10 microM) resulted in a marked decrease in the concentration of Ca2+ required to trigger a threshold response from 0.6 microM to 0.2 microM. The augmentation of Ca2+ sensitivity by ACh was not inhibited by specific protein kinase C inhibitors, calphostin C and K-252b at a concentration of 1 microM. These findings suggest that protein kinase C is not involved in the muscarinic receptor-operated augmentation of Ca2+ sensitivity.", "contents": "Protein kinase C-independent sensitization of contractile proteins to Ca2+ in alpha-toxin-permeabilized smooth muscle cells from the guinea-pig stomach. Involvement of protein kinase C in receptor-operated Ca2+ sensitization of cell shortening was investigated by use of alpha-toxin-permeabilized smooth muscle cells from the fundus of the guinea-pig. Most of the isolated cells responded to 0.6 microM Ca2+ with a maximal shortening to approximately 65% of the resting cell length. Addition of acetylcholine (ACh) at a maximal concentration (10 microM) resulted in a marked decrease in the concentration of Ca2+ required to trigger a threshold response from 0.6 microM to 0.2 microM. The augmentation of Ca2+ sensitivity by ACh was not inhibited by specific protein kinase C inhibitors, calphostin C and K-252b at a concentration of 1 microM. These findings suggest that protein kinase C is not involved in the muscarinic receptor-operated augmentation of Ca2+ sensitivity."} {"id": "PMID:1281723", "title": "Enhanced responsiveness of ovalbumin-sensitized guinea-pig alveolar macrophages to tachykinins.", "content": "1. We have evaluated the ability of substance P (SP), neurokinin A (NKA) and the selective NK2 receptor agonist [beta-Ala8]-NKA(4-10) to induce superoxide anion (O2-) production and prostanoid (prostaglandin E2, thromboxane B2) release from alveolar macrophages (AMs) isolated from control or actively sensitized guinea-pigs. 2. The dose-response curves for NKA and SP were shifted to the left (three orders and one order of magnitude, respectively) in AMs isolated from sensitized animals, with no variation in maximal effects. 3. By evaluating the effects of [beta-Ala8]-NKA(4-10), we observed that not only was the concentration-response curve shifted to the left in both the functional parameters examined, but also maximal effects were significantly enhanced in AMs isolated from sensitized guinea-pigs. 4. This varied responsiveness seems to be specific for tachykinins, as it was not reproduced by another AM stimulant, the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). 5. Only small amounts of beta-glucuronidase were released following tachykinin or ovalbumin stimulation both in control and sensitized AMs. 6. These results indicate that AMs isolated from sensitized guinea-pigs show an increased responsiveness to NK2 receptor stimulation and further stress the role played by AMs in allergic lung diseases.", "contents": "Enhanced responsiveness of ovalbumin-sensitized guinea-pig alveolar macrophages to tachykinins. 1. We have evaluated the ability of substance P (SP), neurokinin A (NKA) and the selective NK2 receptor agonist [beta-Ala8]-NKA(4-10) to induce superoxide anion (O2-) production and prostanoid (prostaglandin E2, thromboxane B2) release from alveolar macrophages (AMs) isolated from control or actively sensitized guinea-pigs. 2. The dose-response curves for NKA and SP were shifted to the left (three orders and one order of magnitude, respectively) in AMs isolated from sensitized animals, with no variation in maximal effects. 3. By evaluating the effects of [beta-Ala8]-NKA(4-10), we observed that not only was the concentration-response curve shifted to the left in both the functional parameters examined, but also maximal effects were significantly enhanced in AMs isolated from sensitized guinea-pigs. 4. This varied responsiveness seems to be specific for tachykinins, as it was not reproduced by another AM stimulant, the bacterial peptide N-formylmethionyl-leucyl-phenylalanine (fMLP). 5. Only small amounts of beta-glucuronidase were released following tachykinin or ovalbumin stimulation both in control and sensitized AMs. 6. These results indicate that AMs isolated from sensitized guinea-pigs show an increased responsiveness to NK2 receptor stimulation and further stress the role played by AMs in allergic lung diseases."} {"id": "PMID:1281724", "title": "Staging of prostate cancer. Accuracy of transrectal ultrasound enhanced by prostate-specific antigen.", "content": "Transrectal ultrasound (TRUS) has shown some promise in the staging of prostate cancer, while prostate-specific antigen (PSA) alone is insufficient. By combining prospective TRUS evaluation with retrospective PSA analysis, we demonstrated an increased accuracy of this combined staging method over TRUS alone. In 48 men undergoing radical prostatectomy, TRUS was performed and PSA measured pre-operatively. On the basis of TRUS, tumours were classified as contained or uncontained. An \"expected\" PSA value was then calculated for each patient as follows: K x volume of hypoechoic area +0.07 x prostate volume where K = 2.1 if the combined Gleason score of the initial biopsy was > or = 7, or 4.2 if the score was < or = 6. If a patient's pre-operative PSA value was less than or equal to the expected PSA, his tumour was judged to be contained. Staging by both TRUS and PSA was combined, so that if the tumour was judged uncontained by either parameter, the combined prediction was uncontained. Results of the combined staging were: sensitivity 84%, specificity 82%, positive predictive value 94%, negative predictive value 60%, accuracy 83%. This PSA formula, which takes into account the size and grade of the lesion rather than an arbitrary cut-off value, enhances the local staging of prostate cancer by TRUS.", "contents": "Staging of prostate cancer. Accuracy of transrectal ultrasound enhanced by prostate-specific antigen. Transrectal ultrasound (TRUS) has shown some promise in the staging of prostate cancer, while prostate-specific antigen (PSA) alone is insufficient. By combining prospective TRUS evaluation with retrospective PSA analysis, we demonstrated an increased accuracy of this combined staging method over TRUS alone. In 48 men undergoing radical prostatectomy, TRUS was performed and PSA measured pre-operatively. On the basis of TRUS, tumours were classified as contained or uncontained. An \"expected\" PSA value was then calculated for each patient as follows: K x volume of hypoechoic area +0.07 x prostate volume where K = 2.1 if the combined Gleason score of the initial biopsy was > or = 7, or 4.2 if the score was < or = 6. If a patient's pre-operative PSA value was less than or equal to the expected PSA, his tumour was judged to be contained. Staging by both TRUS and PSA was combined, so that if the tumour was judged uncontained by either parameter, the combined prediction was uncontained. Results of the combined staging were: sensitivity 84%, specificity 82%, positive predictive value 94%, negative predictive value 60%, accuracy 83%. This PSA formula, which takes into account the size and grade of the lesion rather than an arbitrary cut-off value, enhances the local staging of prostate cancer by TRUS."} {"id": "PMID:1281726", "title": "Placebo-controlled study of terazosin in the treatment of benign prostatic hyperplasia with 2-year follow-up.", "content": "This randomised, placebo-controlled, double-blind study was performed to evaluate the efficacy and safety of once-a-day terazosin (10 mg/d) in ambulatory patients (n = 57) with benign prostatic hyperplasia (BPH). After a 4-week placebo lead-in and a 24-week treatment period with terazosin (with both phases being single-blind), 30 patients who responded to terazosin were randomly assigned to either the terazosin or placebo treatment group for 12 weeks. During the single-blind treatment period, the peak urine flow rate increased 54% from a baseline average of 7.76 ml/s to 11.92 ml/s after terazosin administration; the mean flow rate increased 55% from a baseline of 4.90 ml/s to 7.59 ml/s; and the residual volume decreased 56% from 93.1 ml to 40.7 ml. The mean obstructive symptom score, irritative symptom score and physician global assessment score improved by 68%, 34% and 27%, respectively. All these changes were significant when compared with baseline values. During the double-blind period, the improvement in all the variables was sustained in the terazosin group but not in the placebo group. Peak and mean urinary flow rates, and physician assessment showed significant differences at the end of the double-blind period. Adverse events occurred only during the single-blind period. The most frequently experienced events were headache (n = 6), asthenia (n = 3) and hypotension (n = 3). A follow-up study that initially included 12 patients showed no significant loss of improvement in symptoms and no change in urodynamic parameters with the 5 mg terazosin dose at 1 year. At 2 years, the 9 remaining patients showed sustained improvement and no signs of tachyphylaxis.", "contents": "Placebo-controlled study of terazosin in the treatment of benign prostatic hyperplasia with 2-year follow-up. This randomised, placebo-controlled, double-blind study was performed to evaluate the efficacy and safety of once-a-day terazosin (10 mg/d) in ambulatory patients (n = 57) with benign prostatic hyperplasia (BPH). After a 4-week placebo lead-in and a 24-week treatment period with terazosin (with both phases being single-blind), 30 patients who responded to terazosin were randomly assigned to either the terazosin or placebo treatment group for 12 weeks. During the single-blind treatment period, the peak urine flow rate increased 54% from a baseline average of 7.76 ml/s to 11.92 ml/s after terazosin administration; the mean flow rate increased 55% from a baseline of 4.90 ml/s to 7.59 ml/s; and the residual volume decreased 56% from 93.1 ml to 40.7 ml. The mean obstructive symptom score, irritative symptom score and physician global assessment score improved by 68%, 34% and 27%, respectively. All these changes were significant when compared with baseline values. During the double-blind period, the improvement in all the variables was sustained in the terazosin group but not in the placebo group. Peak and mean urinary flow rates, and physician assessment showed significant differences at the end of the double-blind period. Adverse events occurred only during the single-blind period. The most frequently experienced events were headache (n = 6), asthenia (n = 3) and hypotension (n = 3). A follow-up study that initially included 12 patients showed no significant loss of improvement in symptoms and no change in urodynamic parameters with the 5 mg terazosin dose at 1 year. At 2 years, the 9 remaining patients showed sustained improvement and no signs of tachyphylaxis."} {"id": "PMID:1281727", "title": "Terazosin in the treatment of benign prostatic hyperplasia: a multicentre, placebo-controlled trial.", "content": "The dynamic component of bladder outflow obstruction due to benign prostatic hyperplasia (BPH) has been shown to be modified by alpha 1 adrenergic receptors. Terazosin is an alpha 1 receptor-blocking agent with a long half-life permitting once-daily dosing. This drug was administered in a multicentre, randomised, placebo-controlled trial involving patients with symptomatic bladder outflow obstruction. Of 132 patients recruited for the study, 86 were randomised to receive placebo or terazosin, 81 completed the study, and 80 were considered eligible for efficacy analysis. All terazosin treatment groups showed dramatic improvement in obstructive symptoms when compared with the placebo group, but these differences were not statistically significant because of the small numbers of patients in each group. There were improvements in peak urinary flow rates, mean urinary flow rates, and residual urine volumes for the placebo and terazosin groups, but there were no statistically significant differences in the changes between the groups. Terazosin was well tolerated by patients in this study and may provide symptomatic relief in patients with BPH.", "contents": "Terazosin in the treatment of benign prostatic hyperplasia: a multicentre, placebo-controlled trial. The dynamic component of bladder outflow obstruction due to benign prostatic hyperplasia (BPH) has been shown to be modified by alpha 1 adrenergic receptors. Terazosin is an alpha 1 receptor-blocking agent with a long half-life permitting once-daily dosing. This drug was administered in a multicentre, randomised, placebo-controlled trial involving patients with symptomatic bladder outflow obstruction. Of 132 patients recruited for the study, 86 were randomised to receive placebo or terazosin, 81 completed the study, and 80 were considered eligible for efficacy analysis. All terazosin treatment groups showed dramatic improvement in obstructive symptoms when compared with the placebo group, but these differences were not statistically significant because of the small numbers of patients in each group. There were improvements in peak urinary flow rates, mean urinary flow rates, and residual urine volumes for the placebo and terazosin groups, but there were no statistically significant differences in the changes between the groups. Terazosin was well tolerated by patients in this study and may provide symptomatic relief in patients with BPH."} {"id": "PMID:1281728", "title": "Terazosin in the treatment of benign prostatic hyperplasia: the United States experience.", "content": "The rationale for selective alpha 1 blockade in benign prostatic hyperplasia (BPH) is based upon the observations that the prostate adenoma contains between 20% and 40% smooth muscle and the contractile properties of prostatic smooth muscle are mediated by the alpha 1 adrenoceptor. Terazosin is a selective alpha 1 adrenoceptor antagonist that is currently under clinical investigation for the treatment of clinical BPH. The United States experience with this drug is reviewed in the present report. The outcome measures used to assess the efficacy of terazosin in BPH includes Boyarsky symptom scores and uroflowmetry. The total Boyarsky symptom score decreased 55% and the peak urinary flow increased 47% following terazosin therapy in the cumulative open-label and single-blind studies. Three hundred and thirteen subjects with clinical BPH were randomised into a phase III double-blind parallel-group 3-month placebo-controlled study of once-a-day administration of terazosin. The total Boyarsky symptom score decreased 43% and 21% in the 10 mg and placebo treatment groups, respectively. The peak urinary flow increased 37% and 12% in the 10 mg and placebo-treated groups, respectively. The adverse events associated with terazosin were relatively minor and reversible. The United States experience has unequivocally demonstrated the short-term safety and efficacy of terazosin therapy in BPH. Studies are currently under way to determine the long-term safety and efficacy associated with terazosin therapy in BPH.", "contents": "Terazosin in the treatment of benign prostatic hyperplasia: the United States experience. The rationale for selective alpha 1 blockade in benign prostatic hyperplasia (BPH) is based upon the observations that the prostate adenoma contains between 20% and 40% smooth muscle and the contractile properties of prostatic smooth muscle are mediated by the alpha 1 adrenoceptor. Terazosin is a selective alpha 1 adrenoceptor antagonist that is currently under clinical investigation for the treatment of clinical BPH. The United States experience with this drug is reviewed in the present report. The outcome measures used to assess the efficacy of terazosin in BPH includes Boyarsky symptom scores and uroflowmetry. The total Boyarsky symptom score decreased 55% and the peak urinary flow increased 47% following terazosin therapy in the cumulative open-label and single-blind studies. Three hundred and thirteen subjects with clinical BPH were randomised into a phase III double-blind parallel-group 3-month placebo-controlled study of once-a-day administration of terazosin. The total Boyarsky symptom score decreased 43% and 21% in the 10 mg and placebo treatment groups, respectively. The peak urinary flow increased 37% and 12% in the 10 mg and placebo-treated groups, respectively. The adverse events associated with terazosin were relatively minor and reversible. The United States experience has unequivocally demonstrated the short-term safety and efficacy of terazosin therapy in BPH. Studies are currently under way to determine the long-term safety and efficacy associated with terazosin therapy in BPH."} {"id": "PMID:1281729", "title": "Use of terazosin in the medical treatment of benign prostatic hyperplasia: experience in Italy.", "content": "The purpose of this multicentre, randomised, placebo-controlled, double-blind study was to verify the safety and efficacy of terazosin, an alpha 1 adrenergic blocker, in patients with benign prostatic hyperplasia (BPH). This study involved 137 patients who were randomly assigned to receive either a designed dose of terazosin (2, 5 or 10 mg) or placebo. Response to treatment was measured objectively by uroflowmetric determinations. Subjective evaluation was based on the investigator's assessment of each patient's symptoms. The safety of this agent was monitored by haematological tests and urinalysis. In addition, systolic and diastolic blood pressures and pulse rates were recorded during each visit. The treatment of BPH with terazosin produced a significant improvement in mean flow rate and peak flow rate; there were no statistically significant differences in the analysis of symptomatic responses between the groups of patients treated with terazosin or placebo. Moreover, the safety of this alpha 1 blocker was thoroughly tested and clinically proven.", "contents": "Use of terazosin in the medical treatment of benign prostatic hyperplasia: experience in Italy. The purpose of this multicentre, randomised, placebo-controlled, double-blind study was to verify the safety and efficacy of terazosin, an alpha 1 adrenergic blocker, in patients with benign prostatic hyperplasia (BPH). This study involved 137 patients who were randomly assigned to receive either a designed dose of terazosin (2, 5 or 10 mg) or placebo. Response to treatment was measured objectively by uroflowmetric determinations. Subjective evaluation was based on the investigator's assessment of each patient's symptoms. The safety of this agent was monitored by haematological tests and urinalysis. In addition, systolic and diastolic blood pressures and pulse rates were recorded during each visit. The treatment of BPH with terazosin produced a significant improvement in mean flow rate and peak flow rate; there were no statistically significant differences in the analysis of symptomatic responses between the groups of patients treated with terazosin or placebo. Moreover, the safety of this alpha 1 blocker was thoroughly tested and clinically proven."} {"id": "PMID:1281730", "title": "Future directions in the management of benign prostatic hyperplasia.", "content": "A meeting of the International Consultation on Benign Prostatic Hyperplasia (BPH) in June 1991 provided an update on the management of PBH. It is recognised that the development of complications in what may be regarded as a relatively well tolerated disease may necessitate surgical intervention. Current treatment is directed towards circumventing or ameliorating the complications of BPH and perhaps to find minimally invasive or non-invasive alternatives to surgery that could eliminate this modality altogether. Anticipated changes in the management of BPH include establishment of an improved scoring system and response criteria; implementation of stenting techniques, physical modalities such as hyperthermia and laser therapy to replace transurethral resection of the prostate; development of more specific alpha blockers with fewer adverse effects; and administration of hormonal therapy, possibly as an eventual preventative of BPH. The 1991 International Consultation on Benign Prostatic Hyperplasia (BPH), which took place in Paris, France, under the joint sponsorship or the World Health Organization and the major international and national societies of urology, provided an excellent opportunity to review current knowledge on the subject of BPH and to explore future trends in its management. Most of the information included in this report is drawn from the conclusions of the consultation participants.", "contents": "Future directions in the management of benign prostatic hyperplasia. A meeting of the International Consultation on Benign Prostatic Hyperplasia (BPH) in June 1991 provided an update on the management of PBH. It is recognised that the development of complications in what may be regarded as a relatively well tolerated disease may necessitate surgical intervention. Current treatment is directed towards circumventing or ameliorating the complications of BPH and perhaps to find minimally invasive or non-invasive alternatives to surgery that could eliminate this modality altogether. Anticipated changes in the management of BPH include establishment of an improved scoring system and response criteria; implementation of stenting techniques, physical modalities such as hyperthermia and laser therapy to replace transurethral resection of the prostate; development of more specific alpha blockers with fewer adverse effects; and administration of hormonal therapy, possibly as an eventual preventative of BPH. The 1991 International Consultation on Benign Prostatic Hyperplasia (BPH), which took place in Paris, France, under the joint sponsorship or the World Health Organization and the major international and national societies of urology, provided an excellent opportunity to review current knowledge on the subject of BPH and to explore future trends in its management. Most of the information included in this report is drawn from the conclusions of the consultation participants."} {"id": "PMID:1281731", "title": "Diagnostic challenges of prostatic carcinoma.", "content": "The early detection and staging of prostatic carcinoma are challenging the diagnostic acumen of urologists. Mass screening programmes of asymptomatic men are not justified, as only a small number of cases are diagnosed when the tumour is confined to the prostatic capsule. Diagnostic work-ups of symptomatic men yield a similarly low rate of detection. The most extensively used diagnostic methods include digital rectal examination (DRE), transrectal ultrasound (TRUS) and prostate-specific antigen (PSA) assay. Although DRE is an inexpensive technique that improves early detection, its sensitivity and specificity are low. The specificity and sensitivity of TRUS are higher, but false-positive and false-negative rates are significant. In a study of 566 patients, the rates were 86% and 84%, respectively. A determination of PSA may be informative in the early stages of prostatic cancer, but confirmation of the results by other methods is necessary. Thus, there is no safe method to achieve early diagnosis and precise staging of prostatic carcinoma. Only clinical trials comparing all the different methods will help to establish the definitive role of each one.", "contents": "Diagnostic challenges of prostatic carcinoma. The early detection and staging of prostatic carcinoma are challenging the diagnostic acumen of urologists. Mass screening programmes of asymptomatic men are not justified, as only a small number of cases are diagnosed when the tumour is confined to the prostatic capsule. Diagnostic work-ups of symptomatic men yield a similarly low rate of detection. The most extensively used diagnostic methods include digital rectal examination (DRE), transrectal ultrasound (TRUS) and prostate-specific antigen (PSA) assay. Although DRE is an inexpensive technique that improves early detection, its sensitivity and specificity are low. The specificity and sensitivity of TRUS are higher, but false-positive and false-negative rates are significant. In a study of 566 patients, the rates were 86% and 84%, respectively. A determination of PSA may be informative in the early stages of prostatic cancer, but confirmation of the results by other methods is necessary. Thus, there is no safe method to achieve early diagnosis and precise staging of prostatic carcinoma. Only clinical trials comparing all the different methods will help to establish the definitive role of each one."} {"id": "PMID:1281732", "title": "Laser recanalization versus endoscopic intubation in the palliation of malignant dysphagia: a randomized prospective study.", "content": "Forty patients with histologically confirmed malignant dysphagia were randomized to either endoscopic intubation or laser recanalization. Age, sex, tumour histology and site were evenly distributed between the groups. Results were analysed on an 'intention to treat' basis. All patients treated by laser achieved patency; there was one failed intubation. The best swallowing grade achieved was significantly better with laser recanalization (median 4 (range 3-4)) than with intubation (median 3 (range 2-4)) (P < 0.001). The median survival was 21.5 (range 4-62) weeks in the group receiving laser treatment, compared with 14.5 (range 7-102) weeks in the intubated group (P = 0.09). The median inpatient stay as a proportion of survival time was 14 per cent in the group receiving laser treatment compared with 15 per cent in the intubated group (P > 0.05). The median weight loss was less in the laser-treated patients (2.0 (range 2-8) versus 3.0 (range 0-10) kg, P = 0.04). These results indicate that laser recanalization provides better palliation of dysphagia than does intubation, but this is not reflected in an improvement in survival time.", "contents": "Laser recanalization versus endoscopic intubation in the palliation of malignant dysphagia: a randomized prospective study. Forty patients with histologically confirmed malignant dysphagia were randomized to either endoscopic intubation or laser recanalization. Age, sex, tumour histology and site were evenly distributed between the groups. Results were analysed on an 'intention to treat' basis. All patients treated by laser achieved patency; there was one failed intubation. The best swallowing grade achieved was significantly better with laser recanalization (median 4 (range 3-4)) than with intubation (median 3 (range 2-4)) (P < 0.001). The median survival was 21.5 (range 4-62) weeks in the group receiving laser treatment, compared with 14.5 (range 7-102) weeks in the intubated group (P = 0.09). The median inpatient stay as a proportion of survival time was 14 per cent in the group receiving laser treatment compared with 15 per cent in the intubated group (P > 0.05). The median weight loss was less in the laser-treated patients (2.0 (range 2-8) versus 3.0 (range 0-10) kg, P = 0.04). These results indicate that laser recanalization provides better palliation of dysphagia than does intubation, but this is not reflected in an improvement in survival time."} {"id": "PMID:1281733", "title": "Antihepatitis C virus status in hepatocellular carcinoma and the influence on clinicopathological findings and operative results.", "content": "Antihepatitis C virus (HCV) status was investigated in 100 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) between 1980 and 1989. The clinicopathological findings and operative results, in patients with or without HCV marker, were compared retrospectively. The positivity rate of anti-HCV was 51 per cent. In this group there was a higher mean age, fewer symptoms, raised alanine aminotransferase level, higher 15-min indocyanine green clearance rate and earlier tumour stage compared with the anti-HCV negative group. Positive tumour margins and vascular invasion were seen less frequently in the anti-HCV positive group. HCC with HCV marker showed characteristic features of chronic non-A non-B hepatitis and of HCC originating from liver cirrhosis. There was a better cumulative 1-year survival rate for anti-HCV positive patients, but 3- and 5-year survival rates after hepatectomy were similar in both groups. Although HCV-related HCC had typical features of chronic non-A non-B hepatitis and a relatively early stage of tumour, biological features and operative results were similar with or without the HCV marker.", "contents": "Antihepatitis C virus status in hepatocellular carcinoma and the influence on clinicopathological findings and operative results. Antihepatitis C virus (HCV) status was investigated in 100 patients undergoing hepatectomy for hepatocellular carcinoma (HCC) between 1980 and 1989. The clinicopathological findings and operative results, in patients with or without HCV marker, were compared retrospectively. The positivity rate of anti-HCV was 51 per cent. In this group there was a higher mean age, fewer symptoms, raised alanine aminotransferase level, higher 15-min indocyanine green clearance rate and earlier tumour stage compared with the anti-HCV negative group. Positive tumour margins and vascular invasion were seen less frequently in the anti-HCV positive group. HCC with HCV marker showed characteristic features of chronic non-A non-B hepatitis and of HCC originating from liver cirrhosis. There was a better cumulative 1-year survival rate for anti-HCV positive patients, but 3- and 5-year survival rates after hepatectomy were similar in both groups. Although HCV-related HCC had typical features of chronic non-A non-B hepatitis and a relatively early stage of tumour, biological features and operative results were similar with or without the HCV marker."} {"id": "PMID:1281735", "title": "Distribution of the piriform cortical terminals to cells in the central segment of the mediodorsal thalamic nucleus of the rat.", "content": "A Golgi electron microscopic study was undertaken to investigate the distribution of terminals from the piriform cortex that synapse on identified dendrites of neurons in the central segment of the mediodorsal thalamic nucleus of the rat. The piriform cortical terminals were identified as degenerating terminals following lesions in the cortex. They consisted of two types, i.e., large (LR type) and small (SR type) presynaptic terminals, both of which had round synaptic vesicles and formed asymmetric synaptic contacts. SR boutons terminated preferentially onto distal dendrites and never synapsed on primary dendrites. LR terminals synapsed preferentially on proximal dendrites, but were also found on more distal dendritic segments.", "contents": "Distribution of the piriform cortical terminals to cells in the central segment of the mediodorsal thalamic nucleus of the rat. A Golgi electron microscopic study was undertaken to investigate the distribution of terminals from the piriform cortex that synapse on identified dendrites of neurons in the central segment of the mediodorsal thalamic nucleus of the rat. The piriform cortical terminals were identified as degenerating terminals following lesions in the cortex. They consisted of two types, i.e., large (LR type) and small (SR type) presynaptic terminals, both of which had round synaptic vesicles and formed asymmetric synaptic contacts. SR boutons terminated preferentially onto distal dendrites and never synapsed on primary dendrites. LR terminals synapsed preferentially on proximal dendrites, but were also found on more distal dendritic segments."} {"id": "PMID:1281736", "title": "Substance P and NMDA receptor-mediated slow potentials in neonatal rat spinal cord: age-related changes.", "content": "Slow ventral root potentials (slow VRP's) recorded from 1- to 5-day-old rat spinal cords are implicated in nociception, but there is controversy over their origin and persistence in the adult. The present study investigated changes in the role of substance P and NMDA receptors in slow VRP generation during the postnatal period (1-21 days). Through 9 days, dorsal root stimulation elicits slow VRP's with typical peak amplitudes at 3-4 s, decay time constants of 18-20 s, and durations > 20 s. After 11 days, peak amplitude shortens to < 1 s, decay time constant 4-5 s, and duration < 10 s. At 1-6 days, slow VRP's are sensitive to the NMDA receptor antagonist APV and the substance P antagonists spantide and CP 96,345. After 11 days, APV sensitivity is retained, but spantide and ability of substance P to evoke a response are diminished. Abbreviated slow VRP's in post-11-day spinal cords appear to correspond to the early APV-sensitive component of long-duration slow VRP's in younger animals. Attempts to restore long-duration slow VRP's in 12- to 14-day-old rat cords by blocking various inhibitory mechanisms were not successful. The results suggest that a substance P response, some of which is mediated by NK1 receptors, is lost with maturation of the cord. Either a developmental role played by substance P changes with maturity, or the motor neurons of the isolated post-11-day cord lose the capacity to sustain large long-duration plateau potentials.", "contents": "Substance P and NMDA receptor-mediated slow potentials in neonatal rat spinal cord: age-related changes. Slow ventral root potentials (slow VRP's) recorded from 1- to 5-day-old rat spinal cords are implicated in nociception, but there is controversy over their origin and persistence in the adult. The present study investigated changes in the role of substance P and NMDA receptors in slow VRP generation during the postnatal period (1-21 days). Through 9 days, dorsal root stimulation elicits slow VRP's with typical peak amplitudes at 3-4 s, decay time constants of 18-20 s, and durations > 20 s. After 11 days, peak amplitude shortens to < 1 s, decay time constant 4-5 s, and duration < 10 s. At 1-6 days, slow VRP's are sensitive to the NMDA receptor antagonist APV and the substance P antagonists spantide and CP 96,345. After 11 days, APV sensitivity is retained, but spantide and ability of substance P to evoke a response are diminished. Abbreviated slow VRP's in post-11-day spinal cords appear to correspond to the early APV-sensitive component of long-duration slow VRP's in younger animals. Attempts to restore long-duration slow VRP's in 12- to 14-day-old rat cords by blocking various inhibitory mechanisms were not successful. The results suggest that a substance P response, some of which is mediated by NK1 receptors, is lost with maturation of the cord. Either a developmental role played by substance P changes with maturity, or the motor neurons of the isolated post-11-day cord lose the capacity to sustain large long-duration plateau potentials."} {"id": "PMID:1281737", "title": "Penicillin-induced triphasic modulation of GABAA receptor-operated chloride current in frog sensory neuron.", "content": "Effects of penicillin-G (PCN) on GABA-evoked Cl- current (IGABA) were investigated in freshly dissociated frog sensory neurons by the use of the concentration-clamp technique combined with the suction-pipette method. Under conditions where the internal and external solutions allowed only Cl- permeability, PCN elicited triphasic modulation on IGABA, consisting of two modes of blockade on IGABA and a following rebound (rebound-like transient IGABA). Simultaneously applied PCN and GABA depressed IGABA immediately (phasic blockade), with the depressed IGABA slightly recovering in amplitude to achieve a stable level of blockade (tonic blockade). When a solution containing a mixture or PCN and GABA was quickly replaced by one containing GABA alone, a rebound-like transient Cl- current (IR) was evoked. Each component of the PCN actions on IGABA was PCN- and GABA-concentration-dependent. The reversal potential for each component of the PCN actions on IGABA was close to the chloride equilibrium potential (ECl) calculated using the Nernst equation. The current-voltage (I-V) relations for both the phasic and tonic blockade revealed inward rectification, while I-V curves for the control IGABA and the IR were outwardly rectified. The degree of IGABA-desensitization and the amplitude of the IR correlated well. The data suggest that partial removal of the GABAA receptor-desensitization may result in generation of the IR.", "contents": "Penicillin-induced triphasic modulation of GABAA receptor-operated chloride current in frog sensory neuron. Effects of penicillin-G (PCN) on GABA-evoked Cl- current (IGABA) were investigated in freshly dissociated frog sensory neurons by the use of the concentration-clamp technique combined with the suction-pipette method. Under conditions where the internal and external solutions allowed only Cl- permeability, PCN elicited triphasic modulation on IGABA, consisting of two modes of blockade on IGABA and a following rebound (rebound-like transient IGABA). Simultaneously applied PCN and GABA depressed IGABA immediately (phasic blockade), with the depressed IGABA slightly recovering in amplitude to achieve a stable level of blockade (tonic blockade). When a solution containing a mixture or PCN and GABA was quickly replaced by one containing GABA alone, a rebound-like transient Cl- current (IR) was evoked. Each component of the PCN actions on IGABA was PCN- and GABA-concentration-dependent. The reversal potential for each component of the PCN actions on IGABA was close to the chloride equilibrium potential (ECl) calculated using the Nernst equation. The current-voltage (I-V) relations for both the phasic and tonic blockade revealed inward rectification, while I-V curves for the control IGABA and the IR were outwardly rectified. The degree of IGABA-desensitization and the amplitude of the IR correlated well. The data suggest that partial removal of the GABAA receptor-desensitization may result in generation of the IR."} {"id": "PMID:1281738", "title": "Developmental patterns of intermediate filament gene expression in the normal hamster brain.", "content": "We have examined the patterns of expression of the major intermediate filament (IF) protein mRNAs during development of the hamster brain. Quantitative northern blotting was used to examine changes in the levels of mRNAs for the low, middle and high molecular weight neurofilament proteins (NF-L, NF-M, NF-H) as well as peripherin, vimentin and glial fibrillary acidic protein (GFAP). Total RNA was isolated from hamster brains at embryonic (E) days 12 and 14 and postnatal (P) days 1, 3, 5, 7, 9, 11, 13, 15, 20, 28 and 60-90 (adult), and probed with specific IF cDNAs. Northern blotting revealed that NF-L and NF-M mRNAs were present at very low levels in embryonic brain and that significant expression of these genes only occurred postnatally when the levels increased dramatically until P28 and then declined again in the adult. Increases in NF-H mRNA levels were somewhat delayed relative to those of NF-L and NF-M. NF-H mRNA was not seen at embryonic stages and was expressed at very low levels prior to P9; after that time the levels increased rapidly until P28 and then declined in the adult. Two of the type III IF genes, peripherin and vimentin, followed a pattern of expression opposite that of the NF genes. Both peripherin and vimentin mRNAs were present in embryonic brain and were expressed at higher levels during early postnatal stages than at later times. The magnitude and rate of reduction in vimentin gene expression in the postnatal interval was much greater than that of peripherin. GFAP mRNA levels were extremely low prior to P9 after which a robust increase occurred, followed by a decline in the adult. We discuss the implication of the dramatic changes in IF isotype expression in brain to the pathways of both neuronal and glial development in vivo.", "contents": "Developmental patterns of intermediate filament gene expression in the normal hamster brain. We have examined the patterns of expression of the major intermediate filament (IF) protein mRNAs during development of the hamster brain. Quantitative northern blotting was used to examine changes in the levels of mRNAs for the low, middle and high molecular weight neurofilament proteins (NF-L, NF-M, NF-H) as well as peripherin, vimentin and glial fibrillary acidic protein (GFAP). Total RNA was isolated from hamster brains at embryonic (E) days 12 and 14 and postnatal (P) days 1, 3, 5, 7, 9, 11, 13, 15, 20, 28 and 60-90 (adult), and probed with specific IF cDNAs. Northern blotting revealed that NF-L and NF-M mRNAs were present at very low levels in embryonic brain and that significant expression of these genes only occurred postnatally when the levels increased dramatically until P28 and then declined again in the adult. Increases in NF-H mRNA levels were somewhat delayed relative to those of NF-L and NF-M. NF-H mRNA was not seen at embryonic stages and was expressed at very low levels prior to P9; after that time the levels increased rapidly until P28 and then declined in the adult. Two of the type III IF genes, peripherin and vimentin, followed a pattern of expression opposite that of the NF genes. Both peripherin and vimentin mRNAs were present in embryonic brain and were expressed at higher levels during early postnatal stages than at later times. The magnitude and rate of reduction in vimentin gene expression in the postnatal interval was much greater than that of peripherin. GFAP mRNA levels were extremely low prior to P9 after which a robust increase occurred, followed by a decline in the adult. We discuss the implication of the dramatic changes in IF isotype expression in brain to the pathways of both neuronal and glial development in vivo."} {"id": "PMID:1281739", "title": "Estrogen-concentrating cells within cell groups of the medial preoptic area: sex differences and co-localization with galanin-immunoreactive cells.", "content": "Male and female rats have approximately equal numbers of estrogen(E)-concentrating cells within the medial preoptic area (MPOA). Several cell groups within this brain region are sexually dimorphic, however, and these groups may have sexually different numbers of E-containing cells; this, in turn, may reflect sex differences in neural-regulated functions. In order to study this possibility, the distribution of E-concentrating cells was determined using estrogen autoradiography. Except for the lateral portion of the medial preoptic nucleus (MPNl), the density of E-concentrating cells was 3-5-times higher within the most medially situated cell groups of the female than the male, i.e., within the anteroventral periventricular nucleus (AVPv), periventricular preoptic area (PVPO), medial portion of the medial preoptic nucleus (MPNm), and its central portion (MPNc). In addition, we determined whether E-concentrating cells also express the neuropeptide, galanin. An average of 13% of the E-concentrating cells were galanin positive, which represented 15% of the galanin-immunoreactive population. These results demonstrate a frank and dramatic sex difference in the distribution of E-concentrating cells within sexually dimorphic regions of the MPOA, and also suggest that an interaction between galanin and gonadal steroids may be an important means by which cells within the MPOA regulate reproductive function.", "contents": "Estrogen-concentrating cells within cell groups of the medial preoptic area: sex differences and co-localization with galanin-immunoreactive cells. Male and female rats have approximately equal numbers of estrogen(E)-concentrating cells within the medial preoptic area (MPOA). Several cell groups within this brain region are sexually dimorphic, however, and these groups may have sexually different numbers of E-containing cells; this, in turn, may reflect sex differences in neural-regulated functions. In order to study this possibility, the distribution of E-concentrating cells was determined using estrogen autoradiography. Except for the lateral portion of the medial preoptic nucleus (MPNl), the density of E-concentrating cells was 3-5-times higher within the most medially situated cell groups of the female than the male, i.e., within the anteroventral periventricular nucleus (AVPv), periventricular preoptic area (PVPO), medial portion of the medial preoptic nucleus (MPNm), and its central portion (MPNc). In addition, we determined whether E-concentrating cells also express the neuropeptide, galanin. An average of 13% of the E-concentrating cells were galanin positive, which represented 15% of the galanin-immunoreactive population. These results demonstrate a frank and dramatic sex difference in the distribution of E-concentrating cells within sexually dimorphic regions of the MPOA, and also suggest that an interaction between galanin and gonadal steroids may be an important means by which cells within the MPOA regulate reproductive function."} {"id": "PMID:1281740", "title": "Reversal of learning and memory impairments following lesion of the nucleus basalis magnocellularis (NBM) by concurrent noradrenergic depletion using DSP4 in the rat.", "content": "In the following study the behavioural effects of simultaneous lesion of the nucleus basalis magnocellularis (NBM) using ibotenic acid and noradrenergic depletion following a single i.p. administration of DSP4 (50 mg/kg) were examined in the rat. NBM lesion induced a deficit in acquisition of a reinforced T-maze alternation task, a working memory adaptation of a spatial navigation task in a water maze and 24 h retention in a passive avoidance task compared to sham controls. No effect of the lesion on a reference memory version of spatial navigation in a water maze task was found. Animals that received a combination of NBM lesion and DSP4 treatment showed no impairment on any of the tasks that were impaired by NBM lesion alone. This indicates a reversal of the learning and memory deficits consequent to NBM lesion by simultaneous noradrenergic depletion. NBM lesion induced a significant reduction in choline-acetyltransferase activity in the frontal cortex, and DSP4 induced a significant decrease in noradrenaline concentration in occipital cortex and hippocampus, confirming the effects of these treatments. These results suggest an interaction between central noradrenergic and cholinergic systems in learning and memory processes.", "contents": "Reversal of learning and memory impairments following lesion of the nucleus basalis magnocellularis (NBM) by concurrent noradrenergic depletion using DSP4 in the rat. In the following study the behavioural effects of simultaneous lesion of the nucleus basalis magnocellularis (NBM) using ibotenic acid and noradrenergic depletion following a single i.p. administration of DSP4 (50 mg/kg) were examined in the rat. NBM lesion induced a deficit in acquisition of a reinforced T-maze alternation task, a working memory adaptation of a spatial navigation task in a water maze and 24 h retention in a passive avoidance task compared to sham controls. No effect of the lesion on a reference memory version of spatial navigation in a water maze task was found. Animals that received a combination of NBM lesion and DSP4 treatment showed no impairment on any of the tasks that were impaired by NBM lesion alone. This indicates a reversal of the learning and memory deficits consequent to NBM lesion by simultaneous noradrenergic depletion. NBM lesion induced a significant reduction in choline-acetyltransferase activity in the frontal cortex, and DSP4 induced a significant decrease in noradrenaline concentration in occipital cortex and hippocampus, confirming the effects of these treatments. These results suggest an interaction between central noradrenergic and cholinergic systems in learning and memory processes."} {"id": "PMID:1281741", "title": "Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus.", "content": "The central pressor actions of the tachykinin NK-3 receptor in the paraventricular nucleus (PVN) of the hypothalamus were examined in anesthetized rats. In forebrain-restricted animals, the selective tachykinin NK-3 receptor agonist senktide (10 micrograms, i.c.v.) increased the blood pressure, and this pressor response was more potent than in control animals. Injection of senktide into the PVN also increased the blood pressure, and this pressor response was inhibited by pretreatment with the vasopressin V1 receptor antagonist (10 micrograms/kg, i.v.). These results suggest that central injection of senktide stimulated the NK-3 receptor in the PVN of the hypothalamus, and increased blood pressure by inducing release of vasopressin from the pituitary gland.", "contents": "Central pressor actions of tachykinin NK-3 receptor in the paraventricular nucleus of the rat hypothalamus. The central pressor actions of the tachykinin NK-3 receptor in the paraventricular nucleus (PVN) of the hypothalamus were examined in anesthetized rats. In forebrain-restricted animals, the selective tachykinin NK-3 receptor agonist senktide (10 micrograms, i.c.v.) increased the blood pressure, and this pressor response was more potent than in control animals. Injection of senktide into the PVN also increased the blood pressure, and this pressor response was inhibited by pretreatment with the vasopressin V1 receptor antagonist (10 micrograms/kg, i.v.). These results suggest that central injection of senktide stimulated the NK-3 receptor in the PVN of the hypothalamus, and increased blood pressure by inducing release of vasopressin from the pituitary gland."} {"id": "PMID:1281742", "title": "Ketamine-induced anesthesia involves the N-methyl-D-aspartate receptor-channel complex in mice.", "content": "The role of the N-methyl-D-aspartate (NMDA) receptor-channel complex in ketamine-induced anesthesia was examined in mice. General anesthetic potencies were evaluated on a rating scale, which provided the data for anesthetic scores, loss of righting reflex, sleeping time and recovery time. All drugs were administered intraperitoneally. NMDA (60-300 mg/kg), an NMDA receptor agonist, dose-dependently antagonized the general anesthetic potencies of ketamine at a dose of 100 mg/kg which produced loss of righting reflex in more than 90% of the mice. On the other hand, a high dose of N-methyl-L-aspartate (400 mg/kg), a stereoisomer of NMDA, did not. A dose of 300 mg/kg of NMDA significantly shifted the dose-response curve of ketamine for loss of righting reflex to the right. A high dose of D-cycloserine (200 mg/kg), an agonist at the glycine site on the NMDA receptor complex, slightly but significantly shortened the sleeping time caused by ketamine (100 mg/kg). However, neither a critical subconvulsive dose of kainate (15 mg/kg), a kainate receptor agonist, nor a subconvulsive dose of quisqualate (120 mg/kg), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor agonist, reversed general anesthesia induced by 100 mg/kg of ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Ketamine-induced anesthesia involves the N-methyl-D-aspartate receptor-channel complex in mice. The role of the N-methyl-D-aspartate (NMDA) receptor-channel complex in ketamine-induced anesthesia was examined in mice. General anesthetic potencies were evaluated on a rating scale, which provided the data for anesthetic scores, loss of righting reflex, sleeping time and recovery time. All drugs were administered intraperitoneally. NMDA (60-300 mg/kg), an NMDA receptor agonist, dose-dependently antagonized the general anesthetic potencies of ketamine at a dose of 100 mg/kg which produced loss of righting reflex in more than 90% of the mice. On the other hand, a high dose of N-methyl-L-aspartate (400 mg/kg), a stereoisomer of NMDA, did not. A dose of 300 mg/kg of NMDA significantly shifted the dose-response curve of ketamine for loss of righting reflex to the right. A high dose of D-cycloserine (200 mg/kg), an agonist at the glycine site on the NMDA receptor complex, slightly but significantly shortened the sleeping time caused by ketamine (100 mg/kg). However, neither a critical subconvulsive dose of kainate (15 mg/kg), a kainate receptor agonist, nor a subconvulsive dose of quisqualate (120 mg/kg), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor agonist, reversed general anesthesia induced by 100 mg/kg of ketamine.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281743", "title": "Differential effects of the protein kinase C inhibitors H7 and calphostin C on the cell cycle of neuroblastoma cells.", "content": "We have studied the effect of protein kinase C inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) and calphostin C on the cycle of Neuro-2a cells. Both compounds inhibited cell proliferation and DNA synthesis. Transition from G2 to M phase was not altered by these compounds. Calphostin C blocked the cells in G0/G1, while H7 did not at any specific point in the cell cycle. We also show that the antiproliferative effect induced by both inhibitors is reversible.", "contents": "Differential effects of the protein kinase C inhibitors H7 and calphostin C on the cell cycle of neuroblastoma cells. We have studied the effect of protein kinase C inhibitors 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) and calphostin C on the cycle of Neuro-2a cells. Both compounds inhibited cell proliferation and DNA synthesis. Transition from G2 to M phase was not altered by these compounds. Calphostin C blocked the cells in G0/G1, while H7 did not at any specific point in the cell cycle. We also show that the antiproliferative effect induced by both inhibitors is reversible."} {"id": "PMID:1281744", "title": "Characterization of NK-1 receptors in guinea pig and rat brain membranes with NK-1 peptides and a non-peptide antagonist.", "content": "The major finding of the present investigation is the demonstration of different NK-1 receptors in rat and guinea pig brain membranes with CP 96345 (non-peptide NK-1 antagonist) and R-544 (NK-1 peptide antagonist). We used [3H][Sar9,Met(O2)11]SP, the highly selective ligand for NK-1 receptor to compare NK-1 binding sites in rat and guinea pig brain membranes. Scatchard analysis revealed the existence of a single population of [3H][Sar9,Met(O2)11]SP binding sites in both preparations. The affinity and the maximal number of binding sites were found closely similar in rat (Kd 2 nM, Bmax = 37 fmol/mg protein) and guinea pig brain membranes (Kd = 3 nM, Bmax = 25 fmol/mg of protein). The order of potency of neurokinins to inhibit [3H][Sar9,Met(O2)11]SP binding from rat brain (SP > NKA > NKB) was found different of that observed on guinea pig brain (SP > NKB > NKA). Results obtained with [Sar9,Met(O2)11]SP, [beta Ala8]NKA(4-10) and [MePhe7]NKB suggest that selective agonists cannot discriminate between NK-1 receptors of different species. Using the non-peptide antagonist CP 96345 and the tripeptide R-544, we found that these two NK-1 antagonists discriminate between rat and guinea pig [3H][Sar9,Met(O2)11]SP binding sites.", "contents": "Characterization of NK-1 receptors in guinea pig and rat brain membranes with NK-1 peptides and a non-peptide antagonist. The major finding of the present investigation is the demonstration of different NK-1 receptors in rat and guinea pig brain membranes with CP 96345 (non-peptide NK-1 antagonist) and R-544 (NK-1 peptide antagonist). We used [3H][Sar9,Met(O2)11]SP, the highly selective ligand for NK-1 receptor to compare NK-1 binding sites in rat and guinea pig brain membranes. Scatchard analysis revealed the existence of a single population of [3H][Sar9,Met(O2)11]SP binding sites in both preparations. The affinity and the maximal number of binding sites were found closely similar in rat (Kd 2 nM, Bmax = 37 fmol/mg protein) and guinea pig brain membranes (Kd = 3 nM, Bmax = 25 fmol/mg of protein). The order of potency of neurokinins to inhibit [3H][Sar9,Met(O2)11]SP binding from rat brain (SP > NKA > NKB) was found different of that observed on guinea pig brain (SP > NKB > NKA). Results obtained with [Sar9,Met(O2)11]SP, [beta Ala8]NKA(4-10) and [MePhe7]NKB suggest that selective agonists cannot discriminate between NK-1 receptors of different species. Using the non-peptide antagonist CP 96345 and the tripeptide R-544, we found that these two NK-1 antagonists discriminate between rat and guinea pig [3H][Sar9,Met(O2)11]SP binding sites."} {"id": "PMID:1281745", "title": "Electroconvulsive stimuli and brain peptides: effect of modification of seizure duration on neuropeptide Y, neurokinin A, substance P and neurotensin.", "content": "We studied the effects of modification of duration of seizures induced by electroconvulsive stimuli (ECS) on the changes in concentration of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP) and neurotensin (NT)-like immunoreactivity (-LI) in specific rat brain regions. Rats were divided into groups pretreated with saline, indomethacin, flurbiprofen or diazepam prior to either six sham ECSs or six ECSs. After sacrifice by focused microwave irradiation, brains were dissected into frontal cortex, occipital cortex, striatum, hippocampus, pituitary and hypothalamic sections. Peptides were extracted and measured in extract aliquots by specific radioimmunoassays. Repeated ECS increased NPY-LI and NKA-LI in the hippocampus and the occipital cortex. No effect on SP-LI or NT-LI was found. Indomethacin and flurbiprofen had no effect on the tonic seizure time following ECS, and they did not affect the ECS-induced alterations of the brain peptides. Diazepam pretreatment decreased the tonic seizure time following ECS in a dose-dependent manner. However, diazepam did not modify the ECS-induced increase in NPY-LI and NKA-LI concentrations. The results firmly establish that ECS leads to specific peptide increases in discrete rat brain regions and raise the possibility that such changes may not entirely be a consequence of seizures per se.", "contents": "Electroconvulsive stimuli and brain peptides: effect of modification of seizure duration on neuropeptide Y, neurokinin A, substance P and neurotensin. We studied the effects of modification of duration of seizures induced by electroconvulsive stimuli (ECS) on the changes in concentration of neuropeptide Y (NPY), neurokinin A (NKA), substance P (SP) and neurotensin (NT)-like immunoreactivity (-LI) in specific rat brain regions. Rats were divided into groups pretreated with saline, indomethacin, flurbiprofen or diazepam prior to either six sham ECSs or six ECSs. After sacrifice by focused microwave irradiation, brains were dissected into frontal cortex, occipital cortex, striatum, hippocampus, pituitary and hypothalamic sections. Peptides were extracted and measured in extract aliquots by specific radioimmunoassays. Repeated ECS increased NPY-LI and NKA-LI in the hippocampus and the occipital cortex. No effect on SP-LI or NT-LI was found. Indomethacin and flurbiprofen had no effect on the tonic seizure time following ECS, and they did not affect the ECS-induced alterations of the brain peptides. Diazepam pretreatment decreased the tonic seizure time following ECS in a dose-dependent manner. However, diazepam did not modify the ECS-induced increase in NPY-LI and NKA-LI concentrations. The results firmly establish that ECS leads to specific peptide increases in discrete rat brain regions and raise the possibility that such changes may not entirely be a consequence of seizures per se."} {"id": "PMID:1281746", "title": "Autoradiographic analysis of 125I-substance P binding in rat spinal cord following chronic constriction injury of the sciatic nerve.", "content": "Using receptor binding and autoradiographic techniques, changes in Bolton-Hunter labeled 125I-substance P (125I-BH-SP) binding were determined in laminae I/II, V and X of rat lumbar spinal cord after chronic constriction injury (CCI) of the sciatic nerve. When compared to the sham-operated side of the control group, SP binding significantly increased ipsilateral to the CCI in laminae I/II at 5, 10 and 20 days after injury and in lamina V at 5 days after injury. Scatchard analysis was performed on the 125I-BH-SP binding to the NK1 receptor in laminae I/II of rats 5 days after generation of the CCI. A significant decrease in the Kd of 125I-BH-SP binding was observed in laminae I/II ipsilateral to CCI when compared with the control side (ipsilateral to sham surgery). There was no significant change in the Bmax in laminae I/II ipsilateral to CCI. The changes in 125I-BH-SP binding in the rat spinal cord that occurred after CCI were found in areas of the spinal cord that receive terminations of nociceptive primary afferent fibers. The increased affinity of the NK1 binding site that we report could result in an increase in SP receptor activation in laminae I/II. Such central changes in SP binding may contribute to the neuropathic pain syndrome observed in rats with the CCI.", "contents": "Autoradiographic analysis of 125I-substance P binding in rat spinal cord following chronic constriction injury of the sciatic nerve. Using receptor binding and autoradiographic techniques, changes in Bolton-Hunter labeled 125I-substance P (125I-BH-SP) binding were determined in laminae I/II, V and X of rat lumbar spinal cord after chronic constriction injury (CCI) of the sciatic nerve. When compared to the sham-operated side of the control group, SP binding significantly increased ipsilateral to the CCI in laminae I/II at 5, 10 and 20 days after injury and in lamina V at 5 days after injury. Scatchard analysis was performed on the 125I-BH-SP binding to the NK1 receptor in laminae I/II of rats 5 days after generation of the CCI. A significant decrease in the Kd of 125I-BH-SP binding was observed in laminae I/II ipsilateral to CCI when compared with the control side (ipsilateral to sham surgery). There was no significant change in the Bmax in laminae I/II ipsilateral to CCI. The changes in 125I-BH-SP binding in the rat spinal cord that occurred after CCI were found in areas of the spinal cord that receive terminations of nociceptive primary afferent fibers. The increased affinity of the NK1 binding site that we report could result in an increase in SP receptor activation in laminae I/II. Such central changes in SP binding may contribute to the neuropathic pain syndrome observed in rats with the CCI."} {"id": "PMID:1281747", "title": "Sensitivity of transient outward rectification to ion channel blocking agents in guinea-pig substantia nigra pars compacta neurones in vitro.", "content": "The sensitivity of a transient outward rectifier in guinea-pig substantia nigra pars compacta (SNC) neurones in vitro was tested to a variety of ion channel blocking agents. This rectification was not blocked by TEA (10 mM), 4-aminopyridine (4-AP) (5 mM), apamin (0.2-1 microM) or Cd2+ ions (200 microM). Cs+ ions (5 mM) blocked the inward 'anomalous' rectifier but had no effect on the transient outward rectification. However, replacing Ca2+ ions in the bath perfusate by Ba2+ blocked the transient outward but not the inward rectifier. It is suggested that an atypical barium-sensitive conductance is responsible for the transient outward rectification of these neurones.", "contents": "Sensitivity of transient outward rectification to ion channel blocking agents in guinea-pig substantia nigra pars compacta neurones in vitro. The sensitivity of a transient outward rectifier in guinea-pig substantia nigra pars compacta (SNC) neurones in vitro was tested to a variety of ion channel blocking agents. This rectification was not blocked by TEA (10 mM), 4-aminopyridine (4-AP) (5 mM), apamin (0.2-1 microM) or Cd2+ ions (200 microM). Cs+ ions (5 mM) blocked the inward 'anomalous' rectifier but had no effect on the transient outward rectification. However, replacing Ca2+ ions in the bath perfusate by Ba2+ blocked the transient outward but not the inward rectifier. It is suggested that an atypical barium-sensitive conductance is responsible for the transient outward rectification of these neurones."} {"id": "PMID:1281748", "title": "Synaptic plasticity in the dentate gyrus of aged rats is altered after chronic nimodipine application.", "content": "We examined ultrastructural correlates of synaptic plasticity in the hippocampus of young (3 months) vs aged (30 months) Wistar rats and established the effects of the calcium antagonist nimodipine in animals chronically treated from 24 to 30 months. The effects of nimodipine was studied since this compound improves hippocampal neuronal physiology and enhances cognitive function during aging. In the supragranular layer of the dentate gyrus we found a 24% decrease in synaptic density (Nv) in aged animals, while synaptic size (S) was not significantly altered. After nimodipine treatment Nv in aged rats was not significantly different from young adults, thus being significantly increased compared to age-matched controls. The size of synapses was not significantly altered after nimodipine administration. Total synaptic surface area (Sv) in nimodipine-treated animals was significantly increased compared to aged controls, however, Sv remained significantly lower than in young adults. These data indicate that chronic administration of nimodipine enables granular cells in the dentate gyrus to maintain its number of synaptic contacts during the aging process. Furthermore, the presented influence of nimodipine on synaptic plasticity processes may underlie previously reported improved cognitive functioning of aged animals treated similarly with nimodipine.", "contents": "Synaptic plasticity in the dentate gyrus of aged rats is altered after chronic nimodipine application. We examined ultrastructural correlates of synaptic plasticity in the hippocampus of young (3 months) vs aged (30 months) Wistar rats and established the effects of the calcium antagonist nimodipine in animals chronically treated from 24 to 30 months. The effects of nimodipine was studied since this compound improves hippocampal neuronal physiology and enhances cognitive function during aging. In the supragranular layer of the dentate gyrus we found a 24% decrease in synaptic density (Nv) in aged animals, while synaptic size (S) was not significantly altered. After nimodipine treatment Nv in aged rats was not significantly different from young adults, thus being significantly increased compared to age-matched controls. The size of synapses was not significantly altered after nimodipine administration. Total synaptic surface area (Sv) in nimodipine-treated animals was significantly increased compared to aged controls, however, Sv remained significantly lower than in young adults. These data indicate that chronic administration of nimodipine enables granular cells in the dentate gyrus to maintain its number of synaptic contacts during the aging process. Furthermore, the presented influence of nimodipine on synaptic plasticity processes may underlie previously reported improved cognitive functioning of aged animals treated similarly with nimodipine."} {"id": "PMID:1281749", "title": "Presence of IgG4 on the membrane of human basophils. Histamine release is induced by monoclonal antibodies directed against the Fab but not the Fc region of the IgG4 molecule.", "content": "We have studied the possible role of human IgG4 as an anaphylactic antibody. For that purpose, we have determined the induction of histamine release (HR) from human basophils by anti-IgE and anti-IgG4 monoclonal antibodies (MoAbs) recognizing different epitopes located at the Fc and Fab regions of the IgG4 molecule. The results show that anti-IgG4 (Fab) MoAb was able to induce HR in 93% of donors tested, with no differences between atopics and non-atopics. That HR is calcium dependent and is accompanied by the synthesis and release of leukotriene C4. In contrast, no HR could be induced by anti-IgG4(Fc) MoAbs in any individual, even in the presence of D2O or after a second challenge with a polyclonal goat anti-mouse IgG antibody. The results obtained suggest the presence of IgG4 on the basophil membrane and that the epitope recognized by the anti-IgG4 (Fc) MoAbs is probably hidden in cell-bound IgG4. This was demonstrated by immunofluorescence techniques: IgG4 bound to the basophil membrane could be detected with anti-IgG4(Fab) but not with anti-IgG4(Fc) MoAbs. In addition, we found that nine donors were unresponsive to an anti-IgE stimulus, while they released histamine efficiently after challenge with anti-IgG4(Fab), suggesting the existence of different receptors for both immunoglobulins.", "contents": "Presence of IgG4 on the membrane of human basophils. Histamine release is induced by monoclonal antibodies directed against the Fab but not the Fc region of the IgG4 molecule. We have studied the possible role of human IgG4 as an anaphylactic antibody. For that purpose, we have determined the induction of histamine release (HR) from human basophils by anti-IgE and anti-IgG4 monoclonal antibodies (MoAbs) recognizing different epitopes located at the Fc and Fab regions of the IgG4 molecule. The results show that anti-IgG4 (Fab) MoAb was able to induce HR in 93% of donors tested, with no differences between atopics and non-atopics. That HR is calcium dependent and is accompanied by the synthesis and release of leukotriene C4. In contrast, no HR could be induced by anti-IgG4(Fc) MoAbs in any individual, even in the presence of D2O or after a second challenge with a polyclonal goat anti-mouse IgG antibody. The results obtained suggest the presence of IgG4 on the basophil membrane and that the epitope recognized by the anti-IgG4 (Fc) MoAbs is probably hidden in cell-bound IgG4. This was demonstrated by immunofluorescence techniques: IgG4 bound to the basophil membrane could be detected with anti-IgG4(Fab) but not with anti-IgG4(Fc) MoAbs. In addition, we found that nine donors were unresponsive to an anti-IgE stimulus, while they released histamine efficiently after challenge with anti-IgG4(Fab), suggesting the existence of different receptors for both immunoglobulins."} {"id": "PMID:1281750", "title": "Purification of human blood basophils using negative selection by flow cytometry.", "content": "Basophils were purified from peripheral blood of normal donors using Percoll discontinuous gradients and negative selection by flow cytometry. The mean purity of basophils obtained was 84.7 +/- 4.1 (s.d.)% (range 77.3-90.0%, n = 13). The overall yield of these procedures was 16.0 +/- 2.6% (range 11.0-19.9%, n = 13), and cell viability of purified basophils exceeded 90%. Properties of highly purified basophils obtained by flow cytometry did not differ from those of partially enriched basophil preparations from Percoll discontinuous gradients in respect of: (i) intracellular histamine content; (ii) percentage of spontaneous histamine release in buffer; and (iii) percentage of histamine release triggered by ionophore A 23187 or anti-IgE. Moreover, purified basophils responded chemotactically to complement C5a in a dose-dependent manner. These findings suggest that our procedure for purification of human basophils does not affect the functions of basophils and may be useful for in vitro studies on the role of basophils in hypersensitivity reactions such as bronchial asthma.", "contents": "Purification of human blood basophils using negative selection by flow cytometry. Basophils were purified from peripheral blood of normal donors using Percoll discontinuous gradients and negative selection by flow cytometry. The mean purity of basophils obtained was 84.7 +/- 4.1 (s.d.)% (range 77.3-90.0%, n = 13). The overall yield of these procedures was 16.0 +/- 2.6% (range 11.0-19.9%, n = 13), and cell viability of purified basophils exceeded 90%. Properties of highly purified basophils obtained by flow cytometry did not differ from those of partially enriched basophil preparations from Percoll discontinuous gradients in respect of: (i) intracellular histamine content; (ii) percentage of spontaneous histamine release in buffer; and (iii) percentage of histamine release triggered by ionophore A 23187 or anti-IgE. Moreover, purified basophils responded chemotactically to complement C5a in a dose-dependent manner. These findings suggest that our procedure for purification of human basophils does not affect the functions of basophils and may be useful for in vitro studies on the role of basophils in hypersensitivity reactions such as bronchial asthma."} {"id": "PMID:1281751", "title": "Stability of Candida albicans allergens during storage.", "content": "Stability of Candida albicans allergens was studied under various storage conditions. Lyophilized extract was reconstituted with human serum albumin (NSA) diluent, glycerol-free and in the presence of 10% or 50% glycerol and stored at various temperatures for different time periods. All extracts were tested at the same time with immunoblotting using C. albicans allergic patient sera and galactosidase-labelled anti-IgE. The highest number of detected allergens in the immunoblotting pattern was found in the presence of 50% glycerol at +6 degrees C. The most important allergen of C. albicans, the 46 kD protein allergen was stable up to 10 weeks at +6 degrees C in the presence of 50% glycerol but thereafter began to lose its IgE-binding capacity. After 30 weeks more than 50% of the IgE binding had disappeared. The 27 kD protein, another important allergen, was also labile but retained the allergenicity better than the 46 kD one. The 29 kD protein allergen was stable at all storage conditions, except +37 degrees C tested even after one year. More than 6 months storage at +6 degrees C or higher temperature is, however, unacceptable even in the presence of the 50% glycerol. These findings have particular importance in the diagnosis and treatment of allergic diseases.", "contents": "Stability of Candida albicans allergens during storage. Stability of Candida albicans allergens was studied under various storage conditions. Lyophilized extract was reconstituted with human serum albumin (NSA) diluent, glycerol-free and in the presence of 10% or 50% glycerol and stored at various temperatures for different time periods. All extracts were tested at the same time with immunoblotting using C. albicans allergic patient sera and galactosidase-labelled anti-IgE. The highest number of detected allergens in the immunoblotting pattern was found in the presence of 50% glycerol at +6 degrees C. The most important allergen of C. albicans, the 46 kD protein allergen was stable up to 10 weeks at +6 degrees C in the presence of 50% glycerol but thereafter began to lose its IgE-binding capacity. After 30 weeks more than 50% of the IgE binding had disappeared. The 27 kD protein, another important allergen, was also labile but retained the allergenicity better than the 46 kD one. The 29 kD protein allergen was stable at all storage conditions, except +37 degrees C tested even after one year. More than 6 months storage at +6 degrees C or higher temperature is, however, unacceptable even in the presence of the 50% glycerol. These findings have particular importance in the diagnosis and treatment of allergic diseases."} {"id": "PMID:1281752", "title": "Alteration of intracellular DNA and RNA patterns by liver arginase studied with flow cytometry.", "content": "Previous study of lymphocyte proliferation in the presence of liver arginase has indicated that arginine-depletion in the culture medium plays an important role in inhibiting cell proliferation. The inhibitory effect of both liver arginase and arginine-free condition on DNA, RNA and protein syntheses in PHA-stimulated lymphocytes were studied in cultures by measuring the incorporation of labeled precursors. Simultaneously, their influence on DNA and RNA contents in cells stained by acridine orange was investigated by automated flow cytometry. With 3 micrograms/ml arginase, the syntheses of DNA, RNA and protein were markedly inhibited after 72 h of culture. The degrees of inhibition were close to that induced in an arginine-free condition. The DNA and RNA contents of the individual cell, either cultured with 3 micrograms/ml arginase or in arginine-free medium, were arrested in G0/G1 phase. The results of cell arrest in G0/G1 phase were similar whether the cells were cultured for 24, 48 or 72 h.", "contents": "Alteration of intracellular DNA and RNA patterns by liver arginase studied with flow cytometry. Previous study of lymphocyte proliferation in the presence of liver arginase has indicated that arginine-depletion in the culture medium plays an important role in inhibiting cell proliferation. The inhibitory effect of both liver arginase and arginine-free condition on DNA, RNA and protein syntheses in PHA-stimulated lymphocytes were studied in cultures by measuring the incorporation of labeled precursors. Simultaneously, their influence on DNA and RNA contents in cells stained by acridine orange was investigated by automated flow cytometry. With 3 micrograms/ml arginase, the syntheses of DNA, RNA and protein were markedly inhibited after 72 h of culture. The degrees of inhibition were close to that induced in an arginine-free condition. The DNA and RNA contents of the individual cell, either cultured with 3 micrograms/ml arginase or in arginine-free medium, were arrested in G0/G1 phase. The results of cell arrest in G0/G1 phase were similar whether the cells were cultured for 24, 48 or 72 h."} {"id": "PMID:1281753", "title": "Growth inhibition and modulation of antigenic phenotype in human melanoma and glioblastoma multiforme cells by caffeic acid phenethyl ester (CAPE)", "content": "The active component of the honeybee hive product propolis, caffeic acid phenethyl ester (CAPE), has been shown to display increased toxicity toward various oncogene-transformed cell lines in comparison with their untransformed counterparts (Su et al., 4: 231-242, 1991). This observation provides support for the concept that it is the transformed phenotype which is specifically sensitive to CAPE. In the present study, we have determined the effect of CAPE on the growth and antigenic phenotype of a human melanoma cell line, HO-1, and a human glioblastoma multiforme cell line, GBM-18. For comparison, we have also tested the effects of mezerein (MEZ), mycophenolic acid (MPA) and retinoic acid (RA), which can differentially modulate growth, differentiation and the antigenic phenotype in these human tumor cell lines. Growth of both cell lines was suppressed by CAPE in a dose-dependent fashion, with HO-1 cells being more sensitive than GBM-18 cells. The antiproliferative effect of CAPE was enhanced in both cell types if CAPE and MEZ were used in combination. Growth suppression was associated with morphological changes in H0-1 cells, suggesting induction of a more differentiated phenotype. CAPE also differentially modulated the expression of several antigens on the surface of the two tumor cell lines. These results suggest a potential role for CAPE as an antitumor agent, an antigenic modulating agent and possibly a differentiation inducing agent.", "contents": "Growth inhibition and modulation of antigenic phenotype in human melanoma and glioblastoma multiforme cells by caffeic acid phenethyl ester (CAPE). The active component of the honeybee hive product propolis, caffeic acid phenethyl ester (CAPE), has been shown to display increased toxicity toward various oncogene-transformed cell lines in comparison with their untransformed counterparts (Su et al., 4: 231-242, 1991). This observation provides support for the concept that it is the transformed phenotype which is specifically sensitive to CAPE. In the present study, we have determined the effect of CAPE on the growth and antigenic phenotype of a human melanoma cell line, HO-1, and a human glioblastoma multiforme cell line, GBM-18. For comparison, we have also tested the effects of mezerein (MEZ), mycophenolic acid (MPA) and retinoic acid (RA), which can differentially modulate growth, differentiation and the antigenic phenotype in these human tumor cell lines. Growth of both cell lines was suppressed by CAPE in a dose-dependent fashion, with HO-1 cells being more sensitive than GBM-18 cells. The antiproliferative effect of CAPE was enhanced in both cell types if CAPE and MEZ were used in combination. Growth suppression was associated with morphological changes in H0-1 cells, suggesting induction of a more differentiated phenotype. CAPE also differentially modulated the expression of several antigens on the surface of the two tumor cell lines. These results suggest a potential role for CAPE as an antitumor agent, an antigenic modulating agent and possibly a differentiation inducing agent."} {"id": "PMID:1281754", "title": "Functional and immunological responses of Jurkat lymphocytes transfected with the substance P receptor.", "content": "1. We have transfected the rat substance P receptor (SPR) cDNA into the leukemic T-lymphocyte cell line Jurkat (J-wt) in order to study the effects of substance P (SP) on lymphocyte signaling mechanisms and the resultant neuropeptide-induced immunological changes. 2. The SPR cDNA was transfected into J-wt by the method of electroporation. Clones expressing SPRs were selected using a functional assay that measured SP-induced mobilization of intracellular Ca2+ ([Ca2+]i) in a fluorescence activated cell sorter (FACS) and by their expression of specific 125I-SP binding. 3. One clone, J-SPR, was identified and shown by Northern blot and 125I-SP saturation binding techniques to express the 2.2-kb SPR message and approximately 50,000 SPRs/cell with a Kd of 0.3 nM, respectively. Stimulation of J-SPR by SP resulted in the rapid mobilization of [Ca2+]i. This response was dose dependent in the range 10(-11)-10(-6) M SP and was maximal at 10(-7) M SP, with an EC50 of 0.3-0.5 nM SP. We further demonstrated that the SPR is rapidly desensitized following SP stimulation and by activation of the cell's T-cell receptor (TCR). Whole-cell patch-clamp experiments on J-SPR show that SP stimulation induces a Cl- current by a Ca2+ mediated process dependent on Ca2+/calmodulin-dependent protein kinase (CaMK). 4. Stimulation of J-SPR by SP results in changes in the cell surface expression of a number of molecules that play important roles in cell adhesion and activation: the expression of LFA-1 is decreased, and CD2 and IL-2 receptors are increased by 30 min, 6 hr, and 24 hr, respectively, following stimulation, as assessed by antibody staining in a FACS. 5. The expression of functional SPRs in Jurkat lymphocytes will not permit a detailed examination of how the activation of SPRs result in altered immune responses and further elucidate the role this neuropeptide receptor plays in inflammation.", "contents": "Functional and immunological responses of Jurkat lymphocytes transfected with the substance P receptor. 1. We have transfected the rat substance P receptor (SPR) cDNA into the leukemic T-lymphocyte cell line Jurkat (J-wt) in order to study the effects of substance P (SP) on lymphocyte signaling mechanisms and the resultant neuropeptide-induced immunological changes. 2. The SPR cDNA was transfected into J-wt by the method of electroporation. Clones expressing SPRs were selected using a functional assay that measured SP-induced mobilization of intracellular Ca2+ ([Ca2+]i) in a fluorescence activated cell sorter (FACS) and by their expression of specific 125I-SP binding. 3. One clone, J-SPR, was identified and shown by Northern blot and 125I-SP saturation binding techniques to express the 2.2-kb SPR message and approximately 50,000 SPRs/cell with a Kd of 0.3 nM, respectively. Stimulation of J-SPR by SP resulted in the rapid mobilization of [Ca2+]i. This response was dose dependent in the range 10(-11)-10(-6) M SP and was maximal at 10(-7) M SP, with an EC50 of 0.3-0.5 nM SP. We further demonstrated that the SPR is rapidly desensitized following SP stimulation and by activation of the cell's T-cell receptor (TCR). Whole-cell patch-clamp experiments on J-SPR show that SP stimulation induces a Cl- current by a Ca2+ mediated process dependent on Ca2+/calmodulin-dependent protein kinase (CaMK). 4. Stimulation of J-SPR by SP results in changes in the cell surface expression of a number of molecules that play important roles in cell adhesion and activation: the expression of LFA-1 is decreased, and CD2 and IL-2 receptors are increased by 30 min, 6 hr, and 24 hr, respectively, following stimulation, as assessed by antibody staining in a FACS. 5. The expression of functional SPRs in Jurkat lymphocytes will not permit a detailed examination of how the activation of SPRs result in altered immune responses and further elucidate the role this neuropeptide receptor plays in inflammation."} {"id": "PMID:1281755", "title": "Measles virus-substance P receptor interaction: Jurkat lymphocytes transfected with substance P receptor cDNA enhance measles virus fusion and replication.", "content": "1. We have demonstrated previously (Harrowe et al., 1990), using a lymphoblastoid cell line that constitutively expresses the substance P receptor (SPR) (Payan et al., 1984, 1986), that this receptor may facilitate measles virus (MV) fusion with these cells. In order to test this hypothesis further, a stable cell line transfected with SPR cDNA has been established, and various stages of MV infection in SPR positive and negative cells compared. 2. Jurkat cells, a human T-lymphoblastoid cell line, were transfected with a cDNA clone encoding the SPR. Cells transfected with only the plasmid were used as controls. Jurkat cells and Jurkat vector control cells (J-vo) failed to demonstrate any detectable 125I-SP binding, whereas a clonally selected population of cells transfected with SPR cDNA (J-SPR) expressed about 50,000 receptors/cell (Sudduth-Klinger et al., 1992). 3. Using the J-vo- and J-SPR-transfected cell lines, the following experiments were conducted to investigate the effect of SPR expression on MV infection. To determine if MV would preferentially attach to J-SPR as compared to J-vo, we absorbed virus to cells at 37 degrees C for various times and measured bound MV using a fluorescence activated cell sorter (FACS). Using this approach, we found that MV bound to a greater degree to J-SPR compared with J-vo. In addition to equilibrium being reached faster for J-SPR, the total amount of bound MV was higher on J-SPR. The effect was greater at lower MOIs, suggesting that there existed multiple binding sites for MV on these cells and that the affinity is higher for those cells expressing the SPR. 4. Since binding does not necessitate a successful viral infection, we needed to know if this difference in binding reflected a difference in infection. This was demonstrated by showing an approximate twofold increase in infected cells after a 2-hr binding period with J-SPR as compared to J-vo at an MOI of 1 in an infectious cell-center assay. Moreover, when both cells types were subjected to continuous infection in culture, J-SPR-infected cells produced a seven- to ninefold increase in measles viral titer in 24 hr as compared with J-vo. The observed increase in viral titer may have resulted in more of the J-SPR cells binding virus, as indicated by our binding and infectious cell-center data, or alternatively, the virus might have entered the J-SPR cells faster and begun replication before the J-vo-infected cells.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Measles virus-substance P receptor interaction: Jurkat lymphocytes transfected with substance P receptor cDNA enhance measles virus fusion and replication. 1. We have demonstrated previously (Harrowe et al., 1990), using a lymphoblastoid cell line that constitutively expresses the substance P receptor (SPR) (Payan et al., 1984, 1986), that this receptor may facilitate measles virus (MV) fusion with these cells. In order to test this hypothesis further, a stable cell line transfected with SPR cDNA has been established, and various stages of MV infection in SPR positive and negative cells compared. 2. Jurkat cells, a human T-lymphoblastoid cell line, were transfected with a cDNA clone encoding the SPR. Cells transfected with only the plasmid were used as controls. Jurkat cells and Jurkat vector control cells (J-vo) failed to demonstrate any detectable 125I-SP binding, whereas a clonally selected population of cells transfected with SPR cDNA (J-SPR) expressed about 50,000 receptors/cell (Sudduth-Klinger et al., 1992). 3. Using the J-vo- and J-SPR-transfected cell lines, the following experiments were conducted to investigate the effect of SPR expression on MV infection. To determine if MV would preferentially attach to J-SPR as compared to J-vo, we absorbed virus to cells at 37 degrees C for various times and measured bound MV using a fluorescence activated cell sorter (FACS). Using this approach, we found that MV bound to a greater degree to J-SPR compared with J-vo. In addition to equilibrium being reached faster for J-SPR, the total amount of bound MV was higher on J-SPR. The effect was greater at lower MOIs, suggesting that there existed multiple binding sites for MV on these cells and that the affinity is higher for those cells expressing the SPR. 4. Since binding does not necessitate a successful viral infection, we needed to know if this difference in binding reflected a difference in infection. This was demonstrated by showing an approximate twofold increase in infected cells after a 2-hr binding period with J-SPR as compared to J-vo at an MOI of 1 in an infectious cell-center assay. Moreover, when both cells types were subjected to continuous infection in culture, J-SPR-infected cells produced a seven- to ninefold increase in measles viral titer in 24 hr as compared with J-vo. The observed increase in viral titer may have resulted in more of the J-SPR cells binding virus, as indicated by our binding and infectious cell-center data, or alternatively, the virus might have entered the J-SPR cells faster and begun replication before the J-vo-infected cells.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281756", "title": "Modulation of voltage-activated ion currents on identified neurons of Helix pomatia L. by interleukin-1.", "content": "1. The effect of interleukin-1 (IL-1) was studied on voltage-activated ion currents of the identified central neurons of Helix pomatia L. using a two-microelectrode voltage clamp. The voltage-activated inward current (ICa) was decreased, whereas the outward current (I(net) K) was increased by IL-1. 2. IL-1 affects both the transient and the delayed rectifying potassium currents. The IL-1 modulatory effect on the voltage-activated ion currents was voltage and dose dependent. The threshold concentration for IL-1 was 2 U/ml. 3. The proposed modulatory effect of IL-1 appears to have more than one site of action on the neuron membrane ion channels. 4. Rabbit anti-human IL-1 polyclonal antiserum eliminated the IL-1 effects on the voltage-activated inward and outward currents. This is the first report demonstrating a direct effect of IL-1 modulation of voltage-activated ion currents on neurons of mollusks.", "contents": "Modulation of voltage-activated ion currents on identified neurons of Helix pomatia L. by interleukin-1. 1. The effect of interleukin-1 (IL-1) was studied on voltage-activated ion currents of the identified central neurons of Helix pomatia L. using a two-microelectrode voltage clamp. The voltage-activated inward current (ICa) was decreased, whereas the outward current (I(net) K) was increased by IL-1. 2. IL-1 affects both the transient and the delayed rectifying potassium currents. The IL-1 modulatory effect on the voltage-activated ion currents was voltage and dose dependent. The threshold concentration for IL-1 was 2 U/ml. 3. The proposed modulatory effect of IL-1 appears to have more than one site of action on the neuron membrane ion channels. 4. Rabbit anti-human IL-1 polyclonal antiserum eliminated the IL-1 effects on the voltage-activated inward and outward currents. This is the first report demonstrating a direct effect of IL-1 modulation of voltage-activated ion currents on neurons of mollusks."} {"id": "PMID:1281757", "title": "Immunoreactive growth hormone production by human lymphocyte cell lines.", "content": "1. Two human lymphocyte cell lines, a T-cell line and a B-cell line, were shown to produce and secrete immunoreactive growth hormone (irGH). The irGH molecules secreted by the two cell lines appeared to be de novo synthesized and their molecular size was similar to that of pituitary GH as well as irGH secreted by peripheral blood lymphocytes. 2. Affinity-purified irGH molecules had human growth hormone (hGH)-like mitogenic activity on Nb2 cells. These findings indicate that the irGH molecules produced by H9 and IM9 were similar to hGH in structure. 3. However, the irGH messages could not be amplified by polymerase chain reaction (PCR) primers which had been demonstrated to be able to amplify reverse-transcribed hGH messenger RNA successfully, suggesting that the lymphocyte-derived irGH and pituitary hGH are not exactly identical molecules. 4. We conclude that the H9 and IM9 cells produce a growth hormone-related molecule whose structure is different from that in the anterior pituitary.", "contents": "Immunoreactive growth hormone production by human lymphocyte cell lines. 1. Two human lymphocyte cell lines, a T-cell line and a B-cell line, were shown to produce and secrete immunoreactive growth hormone (irGH). The irGH molecules secreted by the two cell lines appeared to be de novo synthesized and their molecular size was similar to that of pituitary GH as well as irGH secreted by peripheral blood lymphocytes. 2. Affinity-purified irGH molecules had human growth hormone (hGH)-like mitogenic activity on Nb2 cells. These findings indicate that the irGH molecules produced by H9 and IM9 were similar to hGH in structure. 3. However, the irGH messages could not be amplified by polymerase chain reaction (PCR) primers which had been demonstrated to be able to amplify reverse-transcribed hGH messenger RNA successfully, suggesting that the lymphocyte-derived irGH and pituitary hGH are not exactly identical molecules. 4. We conclude that the H9 and IM9 cells produce a growth hormone-related molecule whose structure is different from that in the anterior pituitary."} {"id": "PMID:1281760", "title": "IL6 and acute phase plasma proteins in peritoneal fluid of women with endometriosis.", "content": "Several authors have documented signs of chronic inflammation in the pelvis of women with endometriosis. We investigated the possible involvement of interleukin 6 (IL6), an important regulator of inflammation and immunity, in minimal and mild endometriosis by measuring levels of IL6 and proteins (alpha 1-acid glycoprotein, alpha 1-antitrypsin, alpha 2-HS glycoprotein and albumin) the synthesis of which is regulated by IL6, in peritoneal fluid (PF) from infertile women with histologically confirmed endometriosis (stage I and II; n = 28) and from endometriosis-free fertile (n = 14) and infertile women (n = 13). Spontaneous and LPS-induced IL6 secretion by cultured PF macrophages from women with endometriosis (n = 12) and without endometriosis (n = 9) were also studied. No significant differences were observed in the concentrations of the four proteins studied. Immunoreactive IL6 was detected in all three groups, with no significant differences. In contrast, significantly higher levels of IL6 were released by both unstimulated (P = 0.01) and LPS-stimulated (P = 0.006) peritoneal macrophages from the women with endometriosis. We conclude that local IL6 synthesis by activated macrophages may play a role in the endometriosis process.", "contents": "IL6 and acute phase plasma proteins in peritoneal fluid of women with endometriosis. Several authors have documented signs of chronic inflammation in the pelvis of women with endometriosis. We investigated the possible involvement of interleukin 6 (IL6), an important regulator of inflammation and immunity, in minimal and mild endometriosis by measuring levels of IL6 and proteins (alpha 1-acid glycoprotein, alpha 1-antitrypsin, alpha 2-HS glycoprotein and albumin) the synthesis of which is regulated by IL6, in peritoneal fluid (PF) from infertile women with histologically confirmed endometriosis (stage I and II; n = 28) and from endometriosis-free fertile (n = 14) and infertile women (n = 13). Spontaneous and LPS-induced IL6 secretion by cultured PF macrophages from women with endometriosis (n = 12) and without endometriosis (n = 9) were also studied. No significant differences were observed in the concentrations of the four proteins studied. Immunoreactive IL6 was detected in all three groups, with no significant differences. In contrast, significantly higher levels of IL6 were released by both unstimulated (P = 0.01) and LPS-stimulated (P = 0.006) peritoneal macrophages from the women with endometriosis. We conclude that local IL6 synthesis by activated macrophages may play a role in the endometriosis process."} {"id": "PMID:1281758", "title": "Head and neck spindle cell carcinoma: an evaluation of current management.", "content": "Spindle cell carcinoma is an unusual variant of squamous cell carcinoma. The histogenesis of these tumors is controversial, as is the prognosis for patients with spindle cell carcinoma of the head and neck when compared with all squamous cell carcinomas of these sites. Fifteen consecutive nondermal cases of spindle cell carcinoma of the head and neck were reviewed. Six patients had spindle cell carcinoma either in recurrent tumor or in neck metastases following treatment for squamous cell carcinoma where a spindle cell component was not initially noted. Despite aggressive management, 13 patients have died from their disease. The histogenesis and management of spindle cell carcinoma of the head and neck are discussed.", "contents": "Head and neck spindle cell carcinoma: an evaluation of current management. Spindle cell carcinoma is an unusual variant of squamous cell carcinoma. The histogenesis of these tumors is controversial, as is the prognosis for patients with spindle cell carcinoma of the head and neck when compared with all squamous cell carcinomas of these sites. Fifteen consecutive nondermal cases of spindle cell carcinoma of the head and neck were reviewed. Six patients had spindle cell carcinoma either in recurrent tumor or in neck metastases following treatment for squamous cell carcinoma where a spindle cell component was not initially noted. Despite aggressive management, 13 patients have died from their disease. The histogenesis and management of spindle cell carcinoma of the head and neck are discussed."} {"id": "PMID:1281759", "title": "Glucocorticoids in clinical oncology.", "content": "Glucocorticoids have been used in clinical oncology for more than three decades. Their anti-inflammatory action plays a major role in their clinical applications in oncology. The incidence and severity of side effects depend on the total dose and the duration of therapy, but optimal dosages for these drugs have not been determined. Little is known about other risk factors for toxicity. Prednisone and dexamethasone, the two most commonly used drugs, are well absorbed orally and share quantitatively similar pharmacokinetic values. No definite relationship is known between the glucocorticoid blood level (total and unbound concentration) and therapeutic effect. Glucocorticoids play a major role in the treatment of lymphoproliferative disorders and breast cancer, and they often succeed in palliating common symptoms in advanced cancer.", "contents": "Glucocorticoids in clinical oncology. Glucocorticoids have been used in clinical oncology for more than three decades. Their anti-inflammatory action plays a major role in their clinical applications in oncology. The incidence and severity of side effects depend on the total dose and the duration of therapy, but optimal dosages for these drugs have not been determined. Little is known about other risk factors for toxicity. Prednisone and dexamethasone, the two most commonly used drugs, are well absorbed orally and share quantitatively similar pharmacokinetic values. No definite relationship is known between the glucocorticoid blood level (total and unbound concentration) and therapeutic effect. Glucocorticoids play a major role in the treatment of lymphoproliferative disorders and breast cancer, and they often succeed in palliating common symptoms in advanced cancer."} {"id": "PMID:1281762", "title": "Differential isoform profiles of alpha 2-macroglobulin from plasma of patients with chronic-progressive or relapsing-remitting multiple sclerosis.", "content": "Multiple sclerosis (MS) is a human neurological disease for which no clinically useful marker has been identified in blood. This study examined alpha 2-macroglobulin (alpha 2M) from the plasma of six patients with chronic-progressive MS and six with relapsing-remitting disease. The alpha 2M trypsin-binding activity in the plasma from both groups of patients did not differ from normal controls. However, after column isoelectric focusing, consistently less alpha 2M activity was recovered from the MS samples: those from the chronic-progressive and relapsing-remitting disease groups were an average of 43% and 68%, respectively, of controls. The number and isoelectric point (pI) values of the isoforms of the alpha 2M from patients with chronic-progressive disease were similar to controls. The average pI of the major form for both groups was 6.6. By contrast, the average pI of the major form from the patients with relapsing-remitting MS was significantly elevated to 7.1, and this group displayed a significantly higher percentage of total recovered activity above pH 7.0. In eleven of the twelve cases examined, the pI of the major form of alpha 2M correctly correlated with the clinical status of the patient. The original clinical diagnosis of the patients was reassessed by a 9-year retrospective interview which verified that 9 of the 10 patients in the follow-up group retained their original clinical diagnosis. These studies demonstrate differential isoform profiles of native alpha 2M from MS patients with progressive versus remitting disease which may be useful in subclassifying MS patients.", "contents": "Differential isoform profiles of alpha 2-macroglobulin from plasma of patients with chronic-progressive or relapsing-remitting multiple sclerosis. Multiple sclerosis (MS) is a human neurological disease for which no clinically useful marker has been identified in blood. This study examined alpha 2-macroglobulin (alpha 2M) from the plasma of six patients with chronic-progressive MS and six with relapsing-remitting disease. The alpha 2M trypsin-binding activity in the plasma from both groups of patients did not differ from normal controls. However, after column isoelectric focusing, consistently less alpha 2M activity was recovered from the MS samples: those from the chronic-progressive and relapsing-remitting disease groups were an average of 43% and 68%, respectively, of controls. The number and isoelectric point (pI) values of the isoforms of the alpha 2M from patients with chronic-progressive disease were similar to controls. The average pI of the major form for both groups was 6.6. By contrast, the average pI of the major form from the patients with relapsing-remitting MS was significantly elevated to 7.1, and this group displayed a significantly higher percentage of total recovered activity above pH 7.0. In eleven of the twelve cases examined, the pI of the major form of alpha 2M correctly correlated with the clinical status of the patient. The original clinical diagnosis of the patients was reassessed by a 9-year retrospective interview which verified that 9 of the 10 patients in the follow-up group retained their original clinical diagnosis. These studies demonstrate differential isoform profiles of native alpha 2M from MS patients with progressive versus remitting disease which may be useful in subclassifying MS patients."} {"id": "PMID:1281763", "title": "A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 3 (stromelysin-1) using monoclonal antibodies.", "content": "A one-step sandwich enzyme immunoassay (EIA) for matrix metalloproteinase 3 (MMP-3; stromelysin-1) was developed. The assay system used two simultaneous immunoreactions using a solid phase monoclonal antibody and a horseradish peroxidase-labeled monoclonal antibody (Fab'). The sensitivity of the assay system was 20 micrograms/l and linearity was obtained between 31 and 500 micrograms/l. The EIA system was capable of measuring both precursor and active forms of MMP-3 as well as the forms of MMP-3 complexed with tissue inhibitors of metalloproteinases. MMP-3 levels as measured by this assay are significantly higher in the sera of patients with rheumatoid arthritis as compared to those of healthy subjects and patients with osteoarthritis. Immunoblot analyses showed that in the sera and synovial fluids of patients with rheumatoid arthritis, MMP-3 is present in the 59- and 57-kDa precursor forms.", "contents": "A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 3 (stromelysin-1) using monoclonal antibodies. A one-step sandwich enzyme immunoassay (EIA) for matrix metalloproteinase 3 (MMP-3; stromelysin-1) was developed. The assay system used two simultaneous immunoreactions using a solid phase monoclonal antibody and a horseradish peroxidase-labeled monoclonal antibody (Fab'). The sensitivity of the assay system was 20 micrograms/l and linearity was obtained between 31 and 500 micrograms/l. The EIA system was capable of measuring both precursor and active forms of MMP-3 as well as the forms of MMP-3 complexed with tissue inhibitors of metalloproteinases. MMP-3 levels as measured by this assay are significantly higher in the sera of patients with rheumatoid arthritis as compared to those of healthy subjects and patients with osteoarthritis. Immunoblot analyses showed that in the sera and synovial fluids of patients with rheumatoid arthritis, MMP-3 is present in the 59- and 57-kDa precursor forms."} {"id": "PMID:1281764", "title": "[The subcutaneous administration of a NSAID in palliative care].", "content": "Palliate care is concerned with oncologic patients and its aim is to reduce their suffering, i.e. in the first place to eliminate or reduce pain. As a rule, the WHO prescriptions are followed, administering progressively nonsteroid analgesic agents (NSAIDs), weak opioids, strong opioids. The most convenient channels of administration are oral and subcutaneous. So far, NSAIDs could not be given subcutaneously due to the local side effects (pain and irritation at the point of injection) they cause. On the basis of experience with tenoxicam in our Department, subcutaneous administration is suggested. Our study involved 27 subjects with treatment-refractory tumors, in order to assess topical tolerability. In all cases, the drug was administered via a subcutaneous permanent teflon needle-catheter. Tenoxicam was found to have better gastric tolerability compared to other NSAIDs. It can be concluded that for the palliative treatment of cancer patients tenoxicam ampoules are an additional drug that can be administered subcutaneously.", "contents": "[The subcutaneous administration of a NSAID in palliative care]. Palliate care is concerned with oncologic patients and its aim is to reduce their suffering, i.e. in the first place to eliminate or reduce pain. As a rule, the WHO prescriptions are followed, administering progressively nonsteroid analgesic agents (NSAIDs), weak opioids, strong opioids. The most convenient channels of administration are oral and subcutaneous. So far, NSAIDs could not be given subcutaneously due to the local side effects (pain and irritation at the point of injection) they cause. On the basis of experience with tenoxicam in our Department, subcutaneous administration is suggested. Our study involved 27 subjects with treatment-refractory tumors, in order to assess topical tolerability. In all cases, the drug was administered via a subcutaneous permanent teflon needle-catheter. Tenoxicam was found to have better gastric tolerability compared to other NSAIDs. It can be concluded that for the palliative treatment of cancer patients tenoxicam ampoules are an additional drug that can be administered subcutaneously."} {"id": "PMID:1281765", "title": "[Results of high-dose intravenous immunoglobulin treatment of patients with pretibial myxedema and Basedow's disease. Preliminary findings].", "content": "Three patients affected with Graves' ophthalmopathy and pretibial myxoedema have been treated with high dose intravenous immunoglobulins. We have observed in all patients clinical improvement of pretibial myxoedema and a parallel reduction or negativization of the titre of circulating thyroglobulin, microsomal, TSH receptor autoantibodies and of non organ-specific antibodies (antinuclear, anti smooth muscle cells and antimitochondrial autoantibodies). In conclusion the results of this study suggest that intravenous immunoglobulin are effective in the treatment of pretibial myxoedema and probably act by an immunomodulation of autoimmune phenomena.", "contents": "[Results of high-dose intravenous immunoglobulin treatment of patients with pretibial myxedema and Basedow's disease. Preliminary findings]. Three patients affected with Graves' ophthalmopathy and pretibial myxoedema have been treated with high dose intravenous immunoglobulins. We have observed in all patients clinical improvement of pretibial myxoedema and a parallel reduction or negativization of the titre of circulating thyroglobulin, microsomal, TSH receptor autoantibodies and of non organ-specific antibodies (antinuclear, anti smooth muscle cells and antimitochondrial autoantibodies). In conclusion the results of this study suggest that intravenous immunoglobulin are effective in the treatment of pretibial myxoedema and probably act by an immunomodulation of autoimmune phenomena."} {"id": "PMID:1281766", "title": "Distribution of integrins alpha 6 and beta 4 in the rabbit corneal epithelium after anterior keratectomy.", "content": "Integrins are heterodimeric cell-surface receptor glycoproteins involved in cell-matrix and also in cell-cell interactions. The alpha 6 beta 4 integrin heterodimer has been shown to be a component of the hemidesmosome. In response to wounding, hemidesmosomes are disassembled, the epithelium migrates to cover the denuded area, and eventually the hemidesmosomes reappear. In the present investigation the distribution of the integrin alpha 6 and beta 4 subunits after anterior keratectomy was studied by indirect immunohistochemistry. Labeling for the alpha 6 subunit was observed around the entire cell surface, right to the leading edge. The immunoreaction for the beta 4 subunit was confined to the basal cell membrane facing the basement membrane as in the normal cornea. Cells at the leading edge of the migrating epithelium did not show any labeling for beta 4. Patchy labeling for beta 4 was first observed in the region midway between the wound margin and the leading edge. Because integrins are only expressed as heterodimers, the alpha 6 subunit may be complexed with the beta 1 subunit, instead of with beta 4, at the leading edge of the migrating epithelium. We also suggest that this alpha 6 beta 1 heterodimer may play a role in the reformation of the adhesion complex.", "contents": "Distribution of integrins alpha 6 and beta 4 in the rabbit corneal epithelium after anterior keratectomy. Integrins are heterodimeric cell-surface receptor glycoproteins involved in cell-matrix and also in cell-cell interactions. The alpha 6 beta 4 integrin heterodimer has been shown to be a component of the hemidesmosome. In response to wounding, hemidesmosomes are disassembled, the epithelium migrates to cover the denuded area, and eventually the hemidesmosomes reappear. In the present investigation the distribution of the integrin alpha 6 and beta 4 subunits after anterior keratectomy was studied by indirect immunohistochemistry. Labeling for the alpha 6 subunit was observed around the entire cell surface, right to the leading edge. The immunoreaction for the beta 4 subunit was confined to the basal cell membrane facing the basement membrane as in the normal cornea. Cells at the leading edge of the migrating epithelium did not show any labeling for beta 4. Patchy labeling for beta 4 was first observed in the region midway between the wound margin and the leading edge. Because integrins are only expressed as heterodimers, the alpha 6 subunit may be complexed with the beta 1 subunit, instead of with beta 4, at the leading edge of the migrating epithelium. We also suggest that this alpha 6 beta 1 heterodimer may play a role in the reformation of the adhesion complex."} {"id": "PMID:1281767", "title": "Fine-needle aspiration cytology of an endometrioid-like variant of yolk sac tumor.", "content": "A 36-year-old male with a history of immature teratoma and embryonal carcinoma of the testis was admitted to the hospital for abdominal pain and fever. A CT scan revealed a large right abdominal mass. The patient's serum alpha-fetoprotein (AFP) was 46.8 ng/ml (reference < 25 ng/ml). Fine-needle aspiration (FNA) of the mass revealed malignant glandular cells. Chemotherapy was instituted, followed by resection of the large abdominal mass. The tumor was grossly encapsulated, consisting of large areas of necrotic, hemorrhagic tissue surrounded by smaller, multiloculated cysts. Microscopically, the tumor had a villoglandular pattern and variably stratified tall columnar cells. A prominent feature of the columnar cells was supranuclear and subnuclear vacuolization. Intracytoplasmic PAS-positive, diastase-resistant hyaline globules were occasionally present. AFP by immunoperoxidase was prominent within the tumor. This recurrence of the previously diagnosed testicular teratoma with embryonal carcinoma represents a yolk sac tumor with components strongly resembling endometrioid carcinoma, a variant only recently described in eight cases of ovarian origin (Clement et al.: Am J Surg Pathol 1987; 11(10):767-778). We believe this is the first reported case of an endometrioid-like variant of testicular yolk sac tumor and also the first report of the FNA cytology findings in this variant.", "contents": "Fine-needle aspiration cytology of an endometrioid-like variant of yolk sac tumor. A 36-year-old male with a history of immature teratoma and embryonal carcinoma of the testis was admitted to the hospital for abdominal pain and fever. A CT scan revealed a large right abdominal mass. The patient's serum alpha-fetoprotein (AFP) was 46.8 ng/ml (reference < 25 ng/ml). Fine-needle aspiration (FNA) of the mass revealed malignant glandular cells. Chemotherapy was instituted, followed by resection of the large abdominal mass. The tumor was grossly encapsulated, consisting of large areas of necrotic, hemorrhagic tissue surrounded by smaller, multiloculated cysts. Microscopically, the tumor had a villoglandular pattern and variably stratified tall columnar cells. A prominent feature of the columnar cells was supranuclear and subnuclear vacuolization. Intracytoplasmic PAS-positive, diastase-resistant hyaline globules were occasionally present. AFP by immunoperoxidase was prominent within the tumor. This recurrence of the previously diagnosed testicular teratoma with embryonal carcinoma represents a yolk sac tumor with components strongly resembling endometrioid carcinoma, a variant only recently described in eight cases of ovarian origin (Clement et al.: Am J Surg Pathol 1987; 11(10):767-778). We believe this is the first reported case of an endometrioid-like variant of testicular yolk sac tumor and also the first report of the FNA cytology findings in this variant."} {"id": "PMID:1281768", "title": "Improving health status in extremely low birthweight children between two and five years.", "content": "The 5-year outcome of 101 extremely low birthweight (ELBW, < 1000 g) children discharged from the Neonatal Intensive Care Unit was reported. Over this period, there were four post-discharge deaths. The neurodevelopmental impairment rate was 18% overall: cerebral palsy 7%, blindness 3%, deafness 3% and developmental delay 10%. Seventy-one percent of children were readmitted to hospital. The mean number of admissions was 2.4 per child and the mean duration of total hospital stay was 11.3 days per child in the 5-year period. A trend was observed in a reduction in the readmission rate and hospital days in the 2-5-year period compared to the period between discharge and 2 years, though the differences were not statistically significant. The most common reason for readmission was for surgical procedures, primarily aural ventilation tube insertion and tonsillectomy and adenoidectomy. Significant health problems included recurrent wheezing episodes, stridor and croup in the period up to 2 years and otitis media and tonsillitis between 2 and 5 years. There was some catch-up growth, especially in height, between 2 and 5 years. Children with < 800 g birthweight had similar rates of neurodevelopmental impairment and hospital readmission to those of 800-999 g birthweight. However, they experienced more otitis media and pneumonia, had more ear, nose and throat operations, and at 5 years of age, more were below the 3rd centile for weight. This study showed that the health status of ELBW children had improved between 2 and 5 years, but they continued to experience recurrent health problems and hospital readmissions which would have resulted in added financial and emotional burdens to their families.", "contents": "Improving health status in extremely low birthweight children between two and five years. The 5-year outcome of 101 extremely low birthweight (ELBW, < 1000 g) children discharged from the Neonatal Intensive Care Unit was reported. Over this period, there were four post-discharge deaths. The neurodevelopmental impairment rate was 18% overall: cerebral palsy 7%, blindness 3%, deafness 3% and developmental delay 10%. Seventy-one percent of children were readmitted to hospital. The mean number of admissions was 2.4 per child and the mean duration of total hospital stay was 11.3 days per child in the 5-year period. A trend was observed in a reduction in the readmission rate and hospital days in the 2-5-year period compared to the period between discharge and 2 years, though the differences were not statistically significant. The most common reason for readmission was for surgical procedures, primarily aural ventilation tube insertion and tonsillectomy and adenoidectomy. Significant health problems included recurrent wheezing episodes, stridor and croup in the period up to 2 years and otitis media and tonsillitis between 2 and 5 years. There was some catch-up growth, especially in height, between 2 and 5 years. Children with < 800 g birthweight had similar rates of neurodevelopmental impairment and hospital readmission to those of 800-999 g birthweight. However, they experienced more otitis media and pneumonia, had more ear, nose and throat operations, and at 5 years of age, more were below the 3rd centile for weight. This study showed that the health status of ELBW children had improved between 2 and 5 years, but they continued to experience recurrent health problems and hospital readmissions which would have resulted in added financial and emotional burdens to their families."} {"id": "PMID:1281769", "title": "Multilocus enzyme electrophoresis of major O-antigen reference strains of Pseudomonas aeruginosa.", "content": "Multilocus enzyme electrophoresis was used to characterize 27 Pseudomonas aeruginosa serogroup reference strains used in the major O-antigen schemes according to which Pseudomonas aeruginosa has been typed. Sixteen enzyme loci were assayed, ten of which showed electrophoretic variation. Genetic diversity was expressed for each enzyme locus, and as the mean allelic diversity of loci. Ten electrophoretic types were identified among the strains. The genetic distance between pairs of electrophoretic types was expressed as the proportion of loci at which similar alleles occurred. More than 80% similarity was observed between any pair of electrophoretic types, reflecting the homogeneity of multilocus genotypes within this species. Similarity between electrophoretic types was represented in the form of a dendrogram and by multi-dimensional scaling. Three distinct clusters of electrophoretic types were revealed; within each the serogroups appeared to be randomly distributed.", "contents": "Multilocus enzyme electrophoresis of major O-antigen reference strains of Pseudomonas aeruginosa. Multilocus enzyme electrophoresis was used to characterize 27 Pseudomonas aeruginosa serogroup reference strains used in the major O-antigen schemes according to which Pseudomonas aeruginosa has been typed. Sixteen enzyme loci were assayed, ten of which showed electrophoretic variation. Genetic diversity was expressed for each enzyme locus, and as the mean allelic diversity of loci. Ten electrophoretic types were identified among the strains. The genetic distance between pairs of electrophoretic types was expressed as the proportion of loci at which similar alleles occurred. More than 80% similarity was observed between any pair of electrophoretic types, reflecting the homogeneity of multilocus genotypes within this species. Similarity between electrophoretic types was represented in the form of a dendrogram and by multi-dimensional scaling. Three distinct clusters of electrophoretic types were revealed; within each the serogroups appeared to be randomly distributed."} {"id": "PMID:1281770", "title": "Genome fingerprinting by pulsed-field gel electrophoresis and ribotyping to differentiate Pseudomonas aeruginosa serotype O11 strains.", "content": "The performance of ribotyping and pulsed-field gel electrophoresis was compared in the differentiation of a collection of 44 Pseudomonas aeruginosa serotype O11 strains isolated in seven hospitals in Singapore. Digestion of genomic DNA by EcoRI and SacI followed by Southern hybridization with the Pseudomonas aeruginosa 16S and 23S rRNA gene revealed seven distinct ribotypes. Ribotyping using a combination of both enzymes revealed 11 ribotypes. In contrast, electrophoretic analysis differentiated 41 different strain types among the 44 clinical isolates using either SpeI or DraI. Pulsed-field gel electrophoresis demonstrated greater sensitivity than ribotyping in the differentiation of Pseudomonas aeruginosa strains of the same ribotype and could thus be used alone in epidemiological investigations of hospital outbreaks of Pseudomonas aeruginosa serotype O11 infection.", "contents": "Genome fingerprinting by pulsed-field gel electrophoresis and ribotyping to differentiate Pseudomonas aeruginosa serotype O11 strains. The performance of ribotyping and pulsed-field gel electrophoresis was compared in the differentiation of a collection of 44 Pseudomonas aeruginosa serotype O11 strains isolated in seven hospitals in Singapore. Digestion of genomic DNA by EcoRI and SacI followed by Southern hybridization with the Pseudomonas aeruginosa 16S and 23S rRNA gene revealed seven distinct ribotypes. Ribotyping using a combination of both enzymes revealed 11 ribotypes. In contrast, electrophoretic analysis differentiated 41 different strain types among the 44 clinical isolates using either SpeI or DraI. Pulsed-field gel electrophoresis demonstrated greater sensitivity than ribotyping in the differentiation of Pseudomonas aeruginosa strains of the same ribotype and could thus be used alone in epidemiological investigations of hospital outbreaks of Pseudomonas aeruginosa serotype O11 infection."} {"id": "PMID:1281771", "title": "Characterization of the human gene encoding cytokeratin 17 and its expression pattern.", "content": "Among the members of the cytokeratin (CK) subfamily of intermediate filament (IF) proteins, CK 17 is remarkable as it is normally expressed in the basal cells of complex epithelia but not in stratified or simple epithelia. Because of its unusual expression pattern in normal and diseased states and because of the potential importance of CK 17 in tumor diagnosis, we have characterized the gene(s) and its cDNA-derived amino acid sequence. A cDNA clone encoding CK 17 was isolated from a HeLa cDNA library and used for the determination of the amino acid sequence, for studies of expression and for the screening of human genomic libraries. A number of lambda phage clones were isolated that covered three distinct, non-contiguous gene regions. Only one of these loci contains the functional CK 17 gene which is located only approximately 5 kbp 5'-upstream of the CK 16 gene, whereas the other two contain unprocessed CK 17 pseudogenes. Each of these genes is part of a larger CK type I gene locus the arrangement of which suggests that these genes and pseudogenes have arisen during evolution by duplication events comprising whole multigene loci. The functional CK 17 gene differs from the pseudogenes by the extent of methylation of certain DNA sequences in the 5'-upstream region. The 5 kbp CK 17 gene with 8 exons and 7 introns encodes a polypeptide of 432 amino acids with a calculated molecular weight of 48,000. Using S1-nuclease protection assays and RNAs from several cell lines we identified a single transcriptional start point 26 nucleotides down-stream from a TATA box element. Northern blot hybridization experiments showed a restricted pattern of CK 17 gene expression, supporting the notion that CK 17 synthesis is essentially regulated at the transcriptional level. From these findings and from immunohistological observations, CK 17 synthesis seems to be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial \"stem cells\".", "contents": "Characterization of the human gene encoding cytokeratin 17 and its expression pattern. Among the members of the cytokeratin (CK) subfamily of intermediate filament (IF) proteins, CK 17 is remarkable as it is normally expressed in the basal cells of complex epithelia but not in stratified or simple epithelia. Because of its unusual expression pattern in normal and diseased states and because of the potential importance of CK 17 in tumor diagnosis, we have characterized the gene(s) and its cDNA-derived amino acid sequence. A cDNA clone encoding CK 17 was isolated from a HeLa cDNA library and used for the determination of the amino acid sequence, for studies of expression and for the screening of human genomic libraries. A number of lambda phage clones were isolated that covered three distinct, non-contiguous gene regions. Only one of these loci contains the functional CK 17 gene which is located only approximately 5 kbp 5'-upstream of the CK 16 gene, whereas the other two contain unprocessed CK 17 pseudogenes. Each of these genes is part of a larger CK type I gene locus the arrangement of which suggests that these genes and pseudogenes have arisen during evolution by duplication events comprising whole multigene loci. The functional CK 17 gene differs from the pseudogenes by the extent of methylation of certain DNA sequences in the 5'-upstream region. The 5 kbp CK 17 gene with 8 exons and 7 introns encodes a polypeptide of 432 amino acids with a calculated molecular weight of 48,000. Using S1-nuclease protection assays and RNAs from several cell lines we identified a single transcriptional start point 26 nucleotides down-stream from a TATA box element. Northern blot hybridization experiments showed a restricted pattern of CK 17 gene expression, supporting the notion that CK 17 synthesis is essentially regulated at the transcriptional level. From these findings and from immunohistological observations, CK 17 synthesis seems to be a marker of basal cell differentiation in complex epithelia and therefore indicative of a certain type of epithelial \"stem cells\"."} {"id": "PMID:1281772", "title": "Specific types of prosomes are associated to subnetworks of the intermediate filaments in PtK1 cells.", "content": "Prosomes are small ribonucleoprotein (RNP) particles of unique morphology in the electron microscope but of variable protein and RNA composition, depending on the differentiation state of the cells studied. They were initially observed as subcomplexes of untranslated mRNP. In previous studies, we found that prosomes are associated to the intermediate filaments (IF) of cytokeratin type in HeLa and PtK1 cells. Here we have studied in detail the association of prosomal antigens with the IF networks in PtK1 cells. Contrary to our earlier conclusions, in these cells the vimentin fibers also carry prosomes which, thus, distribute in between the two types of networks. During the selective collapse of the IF induced by acrylamide, and upon recovery after the withdrawal of the drug, no dissociation of the prosome and IF networks of cytokeratin- and vimentin-type could be observed. These data show that even in a dynamic situation, prosome and IF antigens do not dissociate, indicating strongly that they are located on one and the same structure. Furthermore, the differential distribution of specific prosomal antigens between both types of intermediate filament networks indicates that prosomes do not ubiquitously populate the intermediate filaments but occupy subnetworks of either vimentin or cytokeratin type.", "contents": "Specific types of prosomes are associated to subnetworks of the intermediate filaments in PtK1 cells. Prosomes are small ribonucleoprotein (RNP) particles of unique morphology in the electron microscope but of variable protein and RNA composition, depending on the differentiation state of the cells studied. They were initially observed as subcomplexes of untranslated mRNP. In previous studies, we found that prosomes are associated to the intermediate filaments (IF) of cytokeratin type in HeLa and PtK1 cells. Here we have studied in detail the association of prosomal antigens with the IF networks in PtK1 cells. Contrary to our earlier conclusions, in these cells the vimentin fibers also carry prosomes which, thus, distribute in between the two types of networks. During the selective collapse of the IF induced by acrylamide, and upon recovery after the withdrawal of the drug, no dissociation of the prosome and IF networks of cytokeratin- and vimentin-type could be observed. These data show that even in a dynamic situation, prosome and IF antigens do not dissociate, indicating strongly that they are located on one and the same structure. Furthermore, the differential distribution of specific prosomal antigens between both types of intermediate filament networks indicates that prosomes do not ubiquitously populate the intermediate filaments but occupy subnetworks of either vimentin or cytokeratin type."} {"id": "PMID:1281773", "title": "Fibronectin cleavage fragments provide a growth factor-like activity for the differentiation of Trypanosoma cruzi trypomastigotes to amastigotes.", "content": "The morphological and biochemical events following Trypanosoma cruzi trypomastigote-fibronectin (Fn) interactions have been studied. Adhesion of trypomastigotes to Fn-coated surfaces is followed by Fn degradation. The proteolytic cleavage of Fn was demonstrated by qualitative and quantitative measurement of Fn degradation after its exposure to trypomastigotes as well as polyacrylamide gel analysis of Fn proteolysis by a parasite protease (s). The released Fn peptide fragments stimulated the transformation of trypomastigotes to amastigotes. The gelatin (45 kDa) and heparin (40 kDa) binding fragments were shown to be able to promote trypomastigote differentiation. In contrast, native Fn and the 120 kDa fragment (cell attachment domain) were inactive. Complementary investigations showed that the gelatin and heparin binding fragments stimulated parasite RNA synthesis and protein synthesis and phosphorylation but not DNA replication and increased parasite intracellular cAMP concentrations. These findings suggest that the proteolysis of Fn by parasite proteases, which occurs under physiological conditions, might facilitate invasion of target cells by trypomastigotes. The Fn peptides released during this process may act as \"growth factor-like\" substances.", "contents": "Fibronectin cleavage fragments provide a growth factor-like activity for the differentiation of Trypanosoma cruzi trypomastigotes to amastigotes. The morphological and biochemical events following Trypanosoma cruzi trypomastigote-fibronectin (Fn) interactions have been studied. Adhesion of trypomastigotes to Fn-coated surfaces is followed by Fn degradation. The proteolytic cleavage of Fn was demonstrated by qualitative and quantitative measurement of Fn degradation after its exposure to trypomastigotes as well as polyacrylamide gel analysis of Fn proteolysis by a parasite protease (s). The released Fn peptide fragments stimulated the transformation of trypomastigotes to amastigotes. The gelatin (45 kDa) and heparin (40 kDa) binding fragments were shown to be able to promote trypomastigote differentiation. In contrast, native Fn and the 120 kDa fragment (cell attachment domain) were inactive. Complementary investigations showed that the gelatin and heparin binding fragments stimulated parasite RNA synthesis and protein synthesis and phosphorylation but not DNA replication and increased parasite intracellular cAMP concentrations. These findings suggest that the proteolysis of Fn by parasite proteases, which occurs under physiological conditions, might facilitate invasion of target cells by trypomastigotes. The Fn peptides released during this process may act as \"growth factor-like\" substances."} {"id": "PMID:1281774", "title": "Differential effects of various xanthines on pentylenetetrazole-induced seizures in rats: an EEG and behavioural study.", "content": "The present study deals with the EEG (electroencephalogram) and behavioural effects of a subconvulsant dose (30 mg/kg i.p.) of pentylenetetrazole in freely moving rats pretreated (100 mg/kg p.o., 1 h before pentylenetetrazole) with two classic (theophylline and caffeine) and two new (enprofylline and isbufylline) xanthines. In rats treated with vehicle, pentylenetetrazole caused a slight desynchronization of the EEG, characterized by periods of 'wave discharges', and 'spike-and-wave discharge complexes'. In rats pretreated with xanthines (theophylline or caffeine) pentylenetetrazole produced a dramatic increase in ictal seizures with the appearance of continuous spikes; concomitantly animals experienced myoclonic jerks (100%) and in some cases (ca. 20%) the animals died. In contrast, in enprofylline-pretreated rats, pentylenetetrazole induced only brief periods of wave discharges and spike-and-wave discharge complexes whose duration was significantly reduced compared to that of controls, although these discharges were associated with mild epileptic behaviour. When isbufylline-pretreated rats were challenged with pentylenetetrazole, the EEG was characterized by a short run of wave discharges (whose duration was shorter than that of other groups). No enprofylline- or isbufylline-treated rats developed seizures or died. In conclusion, only xanthines with strong adenosine A1 receptor antagonism (theophylline and caffeine) markedly enhance the EEG and behavioural effects of a subconvulsive dose of pentylenetetrazole. The present experimental approach could be used to evaluate the pro-convulsive potential of new xanthine derivatives.", "contents": "Differential effects of various xanthines on pentylenetetrazole-induced seizures in rats: an EEG and behavioural study. The present study deals with the EEG (electroencephalogram) and behavioural effects of a subconvulsant dose (30 mg/kg i.p.) of pentylenetetrazole in freely moving rats pretreated (100 mg/kg p.o., 1 h before pentylenetetrazole) with two classic (theophylline and caffeine) and two new (enprofylline and isbufylline) xanthines. In rats treated with vehicle, pentylenetetrazole caused a slight desynchronization of the EEG, characterized by periods of 'wave discharges', and 'spike-and-wave discharge complexes'. In rats pretreated with xanthines (theophylline or caffeine) pentylenetetrazole produced a dramatic increase in ictal seizures with the appearance of continuous spikes; concomitantly animals experienced myoclonic jerks (100%) and in some cases (ca. 20%) the animals died. In contrast, in enprofylline-pretreated rats, pentylenetetrazole induced only brief periods of wave discharges and spike-and-wave discharge complexes whose duration was significantly reduced compared to that of controls, although these discharges were associated with mild epileptic behaviour. When isbufylline-pretreated rats were challenged with pentylenetetrazole, the EEG was characterized by a short run of wave discharges (whose duration was shorter than that of other groups). No enprofylline- or isbufylline-treated rats developed seizures or died. In conclusion, only xanthines with strong adenosine A1 receptor antagonism (theophylline and caffeine) markedly enhance the EEG and behavioural effects of a subconvulsive dose of pentylenetetrazole. The present experimental approach could be used to evaluate the pro-convulsive potential of new xanthine derivatives."} {"id": "PMID:1281775", "title": "Characterisation of NK receptors in guinea-pig urinary bladder smooth muscle: use of selective antagonists.", "content": "The aim of the present study was to characterise the neurokinin receptors involved in mediating contractile responses in guinea-pig urinary bladder smooth muscle. The use of selective NK1, NK2, and NK3 receptor agonists indicated that contractile responses in this tissue are mediated via activation of NK1 and NK2, but not NK3 receptors. This was confirmed by the observation that responses to [Sar9,Met(O2)11]substance P were inhibited by (+/-)-CP 96,345 (a NK1 receptor antagonist) and responses to eledoisin (following NK1 receptor desensitization) were inhibited by L-659,877 (a NK2 receptor antagonist).", "contents": "Characterisation of NK receptors in guinea-pig urinary bladder smooth muscle: use of selective antagonists. The aim of the present study was to characterise the neurokinin receptors involved in mediating contractile responses in guinea-pig urinary bladder smooth muscle. The use of selective NK1, NK2, and NK3 receptor agonists indicated that contractile responses in this tissue are mediated via activation of NK1 and NK2, but not NK3 receptors. This was confirmed by the observation that responses to [Sar9,Met(O2)11]substance P were inhibited by (+/-)-CP 96,345 (a NK1 receptor antagonist) and responses to eledoisin (following NK1 receptor desensitization) were inhibited by L-659,877 (a NK2 receptor antagonist)."} {"id": "PMID:1281776", "title": "UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms.", "content": "Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (125I-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha 2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha 2, histamine H3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha 2, histamine H3 and somatostatin receptors to treatment of vascular headaches is suggested.", "contents": "UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms. Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (125I-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha 2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha 2, histamine H3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha 2, histamine H3 and somatostatin receptors to treatment of vascular headaches is suggested."} {"id": "PMID:1281777", "title": "Ethanol modulation of GABA receptor-activated Cl- currents in neurons of the chick, rat and mouse central nervous system.", "content": "Modulation of gamma-aminobutyric acidA (GABAA) receptor function by drugs such as ethanol may depend on the genetic heterogeneity of GABAA receptor subunits, which vary across species and cell types. For this reason, the effects of ethanol on gamma-aminobutyric acid receptor-activated chloride currents (IGABA) were examined using whole-cell voltage-clamp recordings in primary cultures of neurons obtained from different species (chick, mouse and rat) and from different brain regions (cerebral cortex, hippocampus, cerebellum and spinal cord), and in acutely dissociated neurons from rat neocortical slices. Low concentrations (1-50 mM) of ethanol produced an enhancement of IGABA in some cells from each brain region examined. In cells obtained from the rat and chick cerebral cortex, 40-58% of cells exhibited an ethanol-sensitive IGABA. Moreover, a statistically significant variation in the response to ethanol was found in rat cortical neurons obtained from different litters. In mouse hippocampal neurons, potentiation of IGABA was obtained with ethanol concentrations (1-10 mM) well below those needed to inhibit neuronal responses to N-methyl-D-aspartic acid (30-50 mM), suggesting a differential sensitivity of these two receptor mechanisms to ethanol. Potentiation of IGABA by ethanol was reversed by the benzodiazepine receptor partial inverse agonist RO15-4513 (ethyl 8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine - 3-carboxylate), but was not affected by chelation of intracellular calcium. Furthermore, high concentrations of GABA attenuated the ability of ethanol to enhance IGABA. These results are consistent with the hypothesis that ethanol facilitates coupling between receptor binding and chloride channel activation.", "contents": "Ethanol modulation of GABA receptor-activated Cl- currents in neurons of the chick, rat and mouse central nervous system. Modulation of gamma-aminobutyric acidA (GABAA) receptor function by drugs such as ethanol may depend on the genetic heterogeneity of GABAA receptor subunits, which vary across species and cell types. For this reason, the effects of ethanol on gamma-aminobutyric acid receptor-activated chloride currents (IGABA) were examined using whole-cell voltage-clamp recordings in primary cultures of neurons obtained from different species (chick, mouse and rat) and from different brain regions (cerebral cortex, hippocampus, cerebellum and spinal cord), and in acutely dissociated neurons from rat neocortical slices. Low concentrations (1-50 mM) of ethanol produced an enhancement of IGABA in some cells from each brain region examined. In cells obtained from the rat and chick cerebral cortex, 40-58% of cells exhibited an ethanol-sensitive IGABA. Moreover, a statistically significant variation in the response to ethanol was found in rat cortical neurons obtained from different litters. In mouse hippocampal neurons, potentiation of IGABA was obtained with ethanol concentrations (1-10 mM) well below those needed to inhibit neuronal responses to N-methyl-D-aspartic acid (30-50 mM), suggesting a differential sensitivity of these two receptor mechanisms to ethanol. Potentiation of IGABA by ethanol was reversed by the benzodiazepine receptor partial inverse agonist RO15-4513 (ethyl 8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine - 3-carboxylate), but was not affected by chelation of intracellular calcium. Furthermore, high concentrations of GABA attenuated the ability of ethanol to enhance IGABA. These results are consistent with the hypothesis that ethanol facilitates coupling between receptor binding and chloride channel activation."} {"id": "PMID:1281778", "title": "Evidence for specific N-terminal galanin fragment binding sites in the rat brain.", "content": "The existence and widespread distribution of specific [125I]galanin-(1-15) fragment binding sites in the rat brain was demonstrated by using [125I]galanin-(1-15) as a radioligand in quantitative receptor autoradiographical studies. These binding sites were also present in several areas lacking or having very few [125I]galanin-(1-29) binding sites, such as the dorsal hippocampal formation, the neocortex and the neostriatum. [125I]Galanin-(1-15) binding sites showed a high selectivity for the fragment, since galanin-(1-15) could displace 80% of the binding whereas porcine galanin-(1-29) could only displace 30%. The binding was saturable with a Kd of 0.63 +/- 0.02 nM and a Bmax of 15.3 +/- 1.7 fmol/mg in sections from the dorsal hippocampal formation. Thus, a new type of galanin receptor selective for N-terminal galanin fragments may exist in the rat brain.", "contents": "Evidence for specific N-terminal galanin fragment binding sites in the rat brain. The existence and widespread distribution of specific [125I]galanin-(1-15) fragment binding sites in the rat brain was demonstrated by using [125I]galanin-(1-15) as a radioligand in quantitative receptor autoradiographical studies. These binding sites were also present in several areas lacking or having very few [125I]galanin-(1-29) binding sites, such as the dorsal hippocampal formation, the neocortex and the neostriatum. [125I]Galanin-(1-15) binding sites showed a high selectivity for the fragment, since galanin-(1-15) could displace 80% of the binding whereas porcine galanin-(1-29) could only displace 30%. The binding was saturable with a Kd of 0.63 +/- 0.02 nM and a Bmax of 15.3 +/- 1.7 fmol/mg in sections from the dorsal hippocampal formation. Thus, a new type of galanin receptor selective for N-terminal galanin fragments may exist in the rat brain."} {"id": "PMID:1281780", "title": "Gene expression of differentiation- and dedifferentiation markers in normal and malignant human thyroid tissues.", "content": "Steady state mRNA transcript levels of thyroid differentiation markers such as TSH receptor (TSHR), thyroglobulin (Tg) and thyroid peroxidase (TPO) as well as a potential marker of dedifferentiation, c-myc, marker were investigated in patients with thyroid tumors and in normal controls using Northern blot analysis. Blots were normalized by acridine orange staining whereas analysis of beta-actin mRNA levels revealed highly variable levels already in normal tissue suggesting regulation of this \"constitutively\" expressed gene. Determination of c-myc mRNA revealed increased steady state mRNA levels in anaplastic carcinomas (ATC) as compared to normal tissues. However, in some patients c-myc transcript levels were lower in the tumor than in the adjacent normal tissue reducing the significance of c-myc as a marker of dedifferentiation. High levels of TSH mRNA were found in control thyroids, whereas in ATC no normal TSHR mRNA was detected. In PTC and follicular thyroid carcinomas (FTC) the transcripts varied from increased to markedly reduced levels. In one patient with FTC 2 independent preparations of the tumor revealed different results, undetectable and clearly detectable TSHR mRNA levels. Xenotransplantation of this tissue on nude rats showed a variable expression pattern in the individual xenotransplantations suggesting heterogeneity of the tumor tissue. Tg and TPO mRNA were strongly expressed in normal tissues and completely lost in all ATC. In differentiated thyroid tumors the transcript levels of Tg and TPO varied from normal to complete loss of expression of either Tg or TPO, or both.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Gene expression of differentiation- and dedifferentiation markers in normal and malignant human thyroid tissues. Steady state mRNA transcript levels of thyroid differentiation markers such as TSH receptor (TSHR), thyroglobulin (Tg) and thyroid peroxidase (TPO) as well as a potential marker of dedifferentiation, c-myc, marker were investigated in patients with thyroid tumors and in normal controls using Northern blot analysis. Blots were normalized by acridine orange staining whereas analysis of beta-actin mRNA levels revealed highly variable levels already in normal tissue suggesting regulation of this \"constitutively\" expressed gene. Determination of c-myc mRNA revealed increased steady state mRNA levels in anaplastic carcinomas (ATC) as compared to normal tissues. However, in some patients c-myc transcript levels were lower in the tumor than in the adjacent normal tissue reducing the significance of c-myc as a marker of dedifferentiation. High levels of TSH mRNA were found in control thyroids, whereas in ATC no normal TSHR mRNA was detected. In PTC and follicular thyroid carcinomas (FTC) the transcripts varied from increased to markedly reduced levels. In one patient with FTC 2 independent preparations of the tumor revealed different results, undetectable and clearly detectable TSHR mRNA levels. Xenotransplantation of this tissue on nude rats showed a variable expression pattern in the individual xenotransplantations suggesting heterogeneity of the tumor tissue. Tg and TPO mRNA were strongly expressed in normal tissues and completely lost in all ATC. In differentiated thyroid tumors the transcript levels of Tg and TPO varied from normal to complete loss of expression of either Tg or TPO, or both.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281781", "title": "Laboratory diagnosis of Mycoplasma pneumoniae infection. 4. Antigen capture and PCR-gene amplification for detection of the Mycoplasma: problems of clinical correlation.", "content": "Direct detection assays for Mycoplasma pneumoniae were established by PCR amplification of short sequences within the foot protein/adhesin (P1) gene and the 16S ribosomal RNA gene. Specificity and sensitivity was excellent, no hybridization was observed with M. genitalium and other human Mycoplasma species. In nose and throat washings from subjects with respiratory infection a pattern of high counts (c.f.u./ml) of M. pneumoniae (deduced from the amount of amplified PCR product), and a positive antigen capture assay, was found in 83% of subjects with serological evidence of current infection with M. pneumoniae. A small proportion of subjects with serological patterns suggesting infection in the more distant past had positive PCR assays. This was considered to represent either persistence of the organism from a previous infection or perhaps transient carriage during a reinfection, without substantial change in antibody response. PCR-based assay of M. pneumoniae offers a powerful, rapid, and sensitive substitute for culture of the mycoplasma. Antigen capture, while less sensitive than PCR, offers the advantage that it is more often positive with samples from current infection and requires less stringent laboratory organization to contain false positive results. We conclude however that the laboratory diagnosis of a chosen clinical episode should not rest on the PCR or Ag-EIA assays alone, but must also include antibody assays to confirm whether infection is current or represents persistence from past exposure.", "contents": "Laboratory diagnosis of Mycoplasma pneumoniae infection. 4. Antigen capture and PCR-gene amplification for detection of the Mycoplasma: problems of clinical correlation. Direct detection assays for Mycoplasma pneumoniae were established by PCR amplification of short sequences within the foot protein/adhesin (P1) gene and the 16S ribosomal RNA gene. Specificity and sensitivity was excellent, no hybridization was observed with M. genitalium and other human Mycoplasma species. In nose and throat washings from subjects with respiratory infection a pattern of high counts (c.f.u./ml) of M. pneumoniae (deduced from the amount of amplified PCR product), and a positive antigen capture assay, was found in 83% of subjects with serological evidence of current infection with M. pneumoniae. A small proportion of subjects with serological patterns suggesting infection in the more distant past had positive PCR assays. This was considered to represent either persistence of the organism from a previous infection or perhaps transient carriage during a reinfection, without substantial change in antibody response. PCR-based assay of M. pneumoniae offers a powerful, rapid, and sensitive substitute for culture of the mycoplasma. Antigen capture, while less sensitive than PCR, offers the advantage that it is more often positive with samples from current infection and requires less stringent laboratory organization to contain false positive results. We conclude however that the laboratory diagnosis of a chosen clinical episode should not rest on the PCR or Ag-EIA assays alone, but must also include antibody assays to confirm whether infection is current or represents persistence from past exposure."} {"id": "PMID:1281782", "title": "Study of early hematopoietic precursors in human cord blood.", "content": "Human cord blood is a source of transplantable stem cells. These stem cells express the antigen CD34, are resistant to treatment with 4-hydroperoxycyclophosphamide (CD34+/4-HCres), and do not give rise to colonies when plated in clonogenic assays. We studied the number of CD34+ cells present in cord blood and developed a two-step assay for early precursors (pre-colony-forming units, pre-CFU) capable of giving rise to committed progenitors. In this assay CD34+/4-HCres cord blood cells were cultured in suspension with different growth factors. After 7 days in suspension the remaining cells were plated in clonogenic assays, for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and mixed lineage colony-forming units (CFU-MIX), in the presence of pure factors or a combination of recombinant human (rh) interleukin 3 (IL-3) and medium conditioned by the PU34 primate cell line. Pre-CFU for all precursors were identified. These pre-CFU developed into committed progenitors in response to rhIL-3. The combinations of rhIL-3 plus rh interleukin 1 (IL-1) or rhIL-3 plus rh interleukin 6 (IL-6) did not enhance recovery of progenitors. The developing CFU-GM were responsive to rh granulocyte-macrophage colony-stimulating factor (GM-CSF) and rh granulocyte colony-stimulating factor (G-CSF) but much less so to rhIL-3. BFU-E and CFU-MIX developed in suspension but could only be detected when cells were replated in the presence of a combination of rhIL-3 and PU34 but not rhIL-3 alone. This assay may be useful in evaluating the number of early hematopoietic precursors present in cord blood samples and in defining growth factor combinations that could enhance hematopoietic recovery after cord blood stem cell transplants.", "contents": "Study of early hematopoietic precursors in human cord blood. Human cord blood is a source of transplantable stem cells. These stem cells express the antigen CD34, are resistant to treatment with 4-hydroperoxycyclophosphamide (CD34+/4-HCres), and do not give rise to colonies when plated in clonogenic assays. We studied the number of CD34+ cells present in cord blood and developed a two-step assay for early precursors (pre-colony-forming units, pre-CFU) capable of giving rise to committed progenitors. In this assay CD34+/4-HCres cord blood cells were cultured in suspension with different growth factors. After 7 days in suspension the remaining cells were plated in clonogenic assays, for granulocyte-macrophage colony-forming units (CFU-GM), erythroid burst-forming units (BFU-E), and mixed lineage colony-forming units (CFU-MIX), in the presence of pure factors or a combination of recombinant human (rh) interleukin 3 (IL-3) and medium conditioned by the PU34 primate cell line. Pre-CFU for all precursors were identified. These pre-CFU developed into committed progenitors in response to rhIL-3. The combinations of rhIL-3 plus rh interleukin 1 (IL-1) or rhIL-3 plus rh interleukin 6 (IL-6) did not enhance recovery of progenitors. The developing CFU-GM were responsive to rh granulocyte-macrophage colony-stimulating factor (GM-CSF) and rh granulocyte colony-stimulating factor (G-CSF) but much less so to rhIL-3. BFU-E and CFU-MIX developed in suspension but could only be detected when cells were replated in the presence of a combination of rhIL-3 and PU34 but not rhIL-3 alone. This assay may be useful in evaluating the number of early hematopoietic precursors present in cord blood samples and in defining growth factor combinations that could enhance hematopoietic recovery after cord blood stem cell transplants."} {"id": "PMID:1281783", "title": "Vanadate mimics the effect of stem cell factor on highly purified human erythroid burst-forming units in vitro, but not the effect of erythropoietin.", "content": "When orthovanadate, an inhibitor of protein tyrosine phosphatase activity, was added to highly purified human blood erythroid burst-forming units (BFU-E) a marked increase in the number and size of erythroid bursts was evident at an optimum concentration of 4 microM. Because BFU-E are stimulated by stem cell factor (SCF), interleukin 3 (IL-3), and erythropoietin (EP), this effect could occur through an enhancement of any one of these pathways. However, no effect was observed on human erythroid colony-forming units (CFU-E), indicating that vanadate was not potentiating the effect of EP. The time course of decline in BFU-E, when vanadate was added in vitro on successive days, followed the time course produced by delayed addition of SCF but not IL-3. In addition, vanadate markedly enhanced the effect of an optimal concentration of IL-3, but it could only enhance the effect of SCF when SCF concentrations were less than optimum. These experiments demonstrate that vanadate markedly stimulates the number and size of human BFU-E in vitro and that it mimics the effect of SCF. Vanadate may be acting as a phosphatase inhibitor that potentiates the kinase activity induced by SCF, but elucidation of its specific biochemical effects on these cells awaits further investigation.", "contents": "Vanadate mimics the effect of stem cell factor on highly purified human erythroid burst-forming units in vitro, but not the effect of erythropoietin. When orthovanadate, an inhibitor of protein tyrosine phosphatase activity, was added to highly purified human blood erythroid burst-forming units (BFU-E) a marked increase in the number and size of erythroid bursts was evident at an optimum concentration of 4 microM. Because BFU-E are stimulated by stem cell factor (SCF), interleukin 3 (IL-3), and erythropoietin (EP), this effect could occur through an enhancement of any one of these pathways. However, no effect was observed on human erythroid colony-forming units (CFU-E), indicating that vanadate was not potentiating the effect of EP. The time course of decline in BFU-E, when vanadate was added in vitro on successive days, followed the time course produced by delayed addition of SCF but not IL-3. In addition, vanadate markedly enhanced the effect of an optimal concentration of IL-3, but it could only enhance the effect of SCF when SCF concentrations were less than optimum. These experiments demonstrate that vanadate markedly stimulates the number and size of human BFU-E in vitro and that it mimics the effect of SCF. Vanadate may be acting as a phosphatase inhibitor that potentiates the kinase activity induced by SCF, but elucidation of its specific biochemical effects on these cells awaits further investigation."} {"id": "PMID:1281784", "title": "Retroviral vector-mediated gene transfer into primitive human hematopoietic progenitor cells: effects of mast cell growth factor (MGF) combined with other cytokines.", "content": "Retroviral vector-mediated gene transfer into human hematopoietic stem cells may permit gene therapy of numerous genetic diseases. Stimulation of marrow with hematopoietic growth factors (HGFs) has been shown to increase the level of retroviral transduction. We have examined the effects of recombinant human mast cell growth factor (MGF), alone and in combination with other HGFs, on the efficiency of gene transfer into human hematopoietic progenitor cells. MGF acts in concert with interleukin 3 (IL-3) and interleukin 6 (IL-6) to increase the percentage of CD34+ progenitors transduced with a retroviral vector expressing the neo gene. The most potent combination of growth factors that we examined, interleukin 1 (IL-1)/IL-3/IL-6/MGF, resulted in the conferral of G418 resistance to 45% of progenitors and long-term culture-initiating cells. Extending the time of cocultivation of the marrow cells with the vector-producing cells did not further increase gene transfer frequency, suggesting that the amount of available vector is not limiting. To analyze the effects of the HGF on gene transfer into more primitive hematopoietic progenitors, CD34+ cells were isolated from marrow samples that were purged of committed progenitor cells by treatment with 4-hydroperoxycyclophosphamide (4-HC). Preculturing the CD34+ 4-HC-treated cells with the combination of four HGF (IL-1/IL-3/IL-6/MGF) permitted transduction of 20%-28% of the progenitors that formed colonies after 30 days in culture. These results demonstrate that MGF in combination with other HGFs enhances gene transduction of human hematopoietic progenitor cells.", "contents": "Retroviral vector-mediated gene transfer into primitive human hematopoietic progenitor cells: effects of mast cell growth factor (MGF) combined with other cytokines. Retroviral vector-mediated gene transfer into human hematopoietic stem cells may permit gene therapy of numerous genetic diseases. Stimulation of marrow with hematopoietic growth factors (HGFs) has been shown to increase the level of retroviral transduction. We have examined the effects of recombinant human mast cell growth factor (MGF), alone and in combination with other HGFs, on the efficiency of gene transfer into human hematopoietic progenitor cells. MGF acts in concert with interleukin 3 (IL-3) and interleukin 6 (IL-6) to increase the percentage of CD34+ progenitors transduced with a retroviral vector expressing the neo gene. The most potent combination of growth factors that we examined, interleukin 1 (IL-1)/IL-3/IL-6/MGF, resulted in the conferral of G418 resistance to 45% of progenitors and long-term culture-initiating cells. Extending the time of cocultivation of the marrow cells with the vector-producing cells did not further increase gene transfer frequency, suggesting that the amount of available vector is not limiting. To analyze the effects of the HGF on gene transfer into more primitive hematopoietic progenitors, CD34+ cells were isolated from marrow samples that were purged of committed progenitor cells by treatment with 4-hydroperoxycyclophosphamide (4-HC). Preculturing the CD34+ 4-HC-treated cells with the combination of four HGF (IL-1/IL-3/IL-6/MGF) permitted transduction of 20%-28% of the progenitors that formed colonies after 30 days in culture. These results demonstrate that MGF in combination with other HGFs enhances gene transduction of human hematopoietic progenitor cells."} {"id": "PMID:1281785", "title": "Increased respiratory burst activity of neutrophils in patients with aplastic anemia: effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor.", "content": "The superoxide (O2-)-releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the priming effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on FMLP-induced O2-release were investigated in neutrophils from 13 patients with aplastic anemia (AA). The O2(-)-releasing capacity of AA neutrophils (0.85 +/- 0.36 nmol/5 min/1 x 10(5) cells, n = 13) was significantly (p < 0.01) increased as compared with that of normal neutrophils (0.24 +/- 0.12 nmol/5 min/1 x 10(5) cells, n = 17). There was no close relationship between the O2(-)-releasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The plasma concentrations of G-CSF and GM-CSF were not elevated to the detectable levels (< 0.1 ng/ml and < 0.2 ng/ml, respectively) in all patients tested. FMLP-induced O2(-)-release was further enhanced by pretreatment of cells with rhG-CSF or rhGM-CSF for 10 min at 37 degrees C, except that no significant priming by rhG-CSF was observed in five patients. The priming effect of rhGM-CSF was consistently greater than that of rhG-CSF in all patients. The i.v. administration of rhGM-CSF (6 micrograms/kg body weight/day) to one patient resulted in an increase in neutrophil O2(-)-release stimulated by FMLP. These findings indicate that neutrophils from AA patients are already primed in vivo for enhanced release of O2- and that these neutrophil functions are further potentiated by rhG-CSF or rhGM-CSF.", "contents": "Increased respiratory burst activity of neutrophils in patients with aplastic anemia: effects of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. The superoxide (O2-)-releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and the priming effects of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on FMLP-induced O2-release were investigated in neutrophils from 13 patients with aplastic anemia (AA). The O2(-)-releasing capacity of AA neutrophils (0.85 +/- 0.36 nmol/5 min/1 x 10(5) cells, n = 13) was significantly (p < 0.01) increased as compared with that of normal neutrophils (0.24 +/- 0.12 nmol/5 min/1 x 10(5) cells, n = 17). There was no close relationship between the O2(-)-releasing capacity and the peripheral blood neutrophil count or the plasma concentration of C-reactive protein. The plasma concentrations of G-CSF and GM-CSF were not elevated to the detectable levels (< 0.1 ng/ml and < 0.2 ng/ml, respectively) in all patients tested. FMLP-induced O2(-)-release was further enhanced by pretreatment of cells with rhG-CSF or rhGM-CSF for 10 min at 37 degrees C, except that no significant priming by rhG-CSF was observed in five patients. The priming effect of rhGM-CSF was consistently greater than that of rhG-CSF in all patients. The i.v. administration of rhGM-CSF (6 micrograms/kg body weight/day) to one patient resulted in an increase in neutrophil O2(-)-release stimulated by FMLP. These findings indicate that neutrophils from AA patients are already primed in vivo for enhanced release of O2- and that these neutrophil functions are further potentiated by rhG-CSF or rhGM-CSF."} {"id": "PMID:1281786", "title": "Canine stem cell factor (c-kit ligand) supports the survival of hematopoietic progenitors in long-term canine marrow culture.", "content": "The cDNA for canine stem cell factor (cSCF, c-kit ligand) was cloned and expressed in Escherichia coli. The recombinant protein (rcSCF), 165 amino acids in length, is very similar structurally to the soluble form of previously cloned and sequenced rodent and human SCFs. The biological effects of rcSCF were studied in a day-10 granulocyte-macrophage colony-forming unit (CFU-GM) clonogenic assay and in long-term liquid bone marrow culture of non-adherent hematopoietic cells in the absence of a stromal underlayer. Synergism in the stimulation of growth of CFU-GM was demonstrated between rcSCF and both recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and naturally occurring colony-stimulating activity present in the serum of a neutropenic dog. Alone, rcSCF was nonstimulatory for committed marrow precursors in methylcellulose cultures and had minimal effect on hematopoietic progenitor cell survival in stromaless, liquid cultures. When rcSCF was combined with phytohemagglutinin-stimulated canine lymphocyte-conditioned medium (PHA-LCM) or rh interleukin 6 (IL-6), with or without rhGM-CSF, CFU-GM survived for up to 5 weeks. The combination of rcSCF and rhGM-CSF, without rhIL-6, led to an early increase in CFU-GM in liquid cultures that declined more rapidly than in flasks that included rhIL-6. Survival of progenitor cells was negligible beyond 1 week in flasks with growth factor combinations lacking rcSCF. Sustained production of nonadherent cells in long-term cultures also was dependent on rcSCF in combination with canine PHA-LCM or recombinant human growth factors. It appears that rcSCF, like that from rodent and primate species, has the ability to influence the survival and proliferation of CFU-GM, and perhaps earlier progenitor cells, in hematopoietic tissues. In a long-term liquid culture system in which growth factor production by stromal cells is limited, rcSCF possesses a unique ability to maintain the viability of progenitor cells for up to 5 weeks.", "contents": "Canine stem cell factor (c-kit ligand) supports the survival of hematopoietic progenitors in long-term canine marrow culture. The cDNA for canine stem cell factor (cSCF, c-kit ligand) was cloned and expressed in Escherichia coli. The recombinant protein (rcSCF), 165 amino acids in length, is very similar structurally to the soluble form of previously cloned and sequenced rodent and human SCFs. The biological effects of rcSCF were studied in a day-10 granulocyte-macrophage colony-forming unit (CFU-GM) clonogenic assay and in long-term liquid bone marrow culture of non-adherent hematopoietic cells in the absence of a stromal underlayer. Synergism in the stimulation of growth of CFU-GM was demonstrated between rcSCF and both recombinant human (rh) granulocyte-macrophage colony-stimulating factor (GM-CSF) and naturally occurring colony-stimulating activity present in the serum of a neutropenic dog. Alone, rcSCF was nonstimulatory for committed marrow precursors in methylcellulose cultures and had minimal effect on hematopoietic progenitor cell survival in stromaless, liquid cultures. When rcSCF was combined with phytohemagglutinin-stimulated canine lymphocyte-conditioned medium (PHA-LCM) or rh interleukin 6 (IL-6), with or without rhGM-CSF, CFU-GM survived for up to 5 weeks. The combination of rcSCF and rhGM-CSF, without rhIL-6, led to an early increase in CFU-GM in liquid cultures that declined more rapidly than in flasks that included rhIL-6. Survival of progenitor cells was negligible beyond 1 week in flasks with growth factor combinations lacking rcSCF. Sustained production of nonadherent cells in long-term cultures also was dependent on rcSCF in combination with canine PHA-LCM or recombinant human growth factors. It appears that rcSCF, like that from rodent and primate species, has the ability to influence the survival and proliferation of CFU-GM, and perhaps earlier progenitor cells, in hematopoietic tissues. In a long-term liquid culture system in which growth factor production by stromal cells is limited, rcSCF possesses a unique ability to maintain the viability of progenitor cells for up to 5 weeks."} {"id": "PMID:1281787", "title": "Insulin and noradrenaline independently stimulate the translocation of glucose transporters from intracellular stores to the plasma membrane in mouse brown adipocytes.", "content": "The mechanism of the effect of noradrenaline on the transport of 3-O-methyl-D-[14C]glucose ([14C]-MG) was studied in mouse brown adipocytes. When cells were exposed to low concentrations (< 10(-8) M) of insulin, the [14C]-MG uptake by cells was enhanced by noradrenaline additively. The action of noradrenaline was mimicked by isoproterenol, and was completely blocked by propranolol. Exposing cells to noradrenaline induced both an increase in the transport activity of plasma membrane fractions and a decrease in that of microsomal fractions similar to insulin exposure, indicating that noradrenaline also induces the translocation of glucose transporters to the plasma membrane. The ratio of an increase in the transport activity of plasma membrane fraction to a decrease in the activity of microsomal fraction was lower in cells exposed to noradrenaline than in cells exposed to insulin. This quantitative disagreement suggests that there are at least two different modes involved in the regulation of the translocation of glucose transporters in mouse brown adipocytes.", "contents": "Insulin and noradrenaline independently stimulate the translocation of glucose transporters from intracellular stores to the plasma membrane in mouse brown adipocytes. The mechanism of the effect of noradrenaline on the transport of 3-O-methyl-D-[14C]glucose ([14C]-MG) was studied in mouse brown adipocytes. When cells were exposed to low concentrations (< 10(-8) M) of insulin, the [14C]-MG uptake by cells was enhanced by noradrenaline additively. The action of noradrenaline was mimicked by isoproterenol, and was completely blocked by propranolol. Exposing cells to noradrenaline induced both an increase in the transport activity of plasma membrane fractions and a decrease in that of microsomal fractions similar to insulin exposure, indicating that noradrenaline also induces the translocation of glucose transporters to the plasma membrane. The ratio of an increase in the transport activity of plasma membrane fraction to a decrease in the activity of microsomal fraction was lower in cells exposed to noradrenaline than in cells exposed to insulin. This quantitative disagreement suggests that there are at least two different modes involved in the regulation of the translocation of glucose transporters in mouse brown adipocytes."} {"id": "PMID:1281788", "title": "Anticodon-dependent aminoacylation of RNA minisubstrate by lysyl-tRNA synthetase.", "content": "Specific inhibition of mammalian lysyl-tRNA synthetase by polyU is shown. Inhibition of the enzyme is dependent on the length of the oligonucleotide, since oligoU molecules with a length of less than 8 residues do not inhibit the aminoacylation, whilst the effect of oligoU molecules with a length of about 30 residues is the same as that of polyU. Inhibition is a result of recognition by the enzyme of the tRNALys anticodon sequence (UUU) coded by polyU. Aminoacylation of the oligoU molecule with attached CCA sequence (G(U)20-CCA) by yeast and mammalian lysyl-tRNA synthetases is demonstrated.", "contents": "Anticodon-dependent aminoacylation of RNA minisubstrate by lysyl-tRNA synthetase. Specific inhibition of mammalian lysyl-tRNA synthetase by polyU is shown. Inhibition of the enzyme is dependent on the length of the oligonucleotide, since oligoU molecules with a length of less than 8 residues do not inhibit the aminoacylation, whilst the effect of oligoU molecules with a length of about 30 residues is the same as that of polyU. Inhibition is a result of recognition by the enzyme of the tRNALys anticodon sequence (UUU) coded by polyU. Aminoacylation of the oligoU molecule with attached CCA sequence (G(U)20-CCA) by yeast and mammalian lysyl-tRNA synthetases is demonstrated."} {"id": "PMID:1281789", "title": "Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes.", "content": "During inflammatory states, hepatocytes are induced to synthesize and secrete a group of proteins called acute-phase proteins. It has recently been shown that besides interleukin-6 (IL-6), related cytokines such as leukemia inhibitory factor, oncostation M and interleukin-11 are also mediators of the hepatic acute-phase response. All these mediators belong to the hematopoietic family of alpha-helical cytokines. Here we show that an additional member of this cytokine family, ciliary neurotrophic factor (CNTF), induces the hepatic acute-phase protein genes haptoglobin, alpha 1-antichymotrypsin, alpha 2-macroglobulin and beta-fibrinogen in human hepatoma cells (HepG2) and in primary rat hepatocytes with a time course and dose-response comparable with that of IL-6. Our next aim was to define the receptor components used by CNTF on hepatic cells. Using a cell-free binding assay we exclude that CNTF binds to the 80 kDa IL-6 receptor, a protein with significant homology to the CNTF receptor which has recently been cloned from neuroblastoma cells. In human hepatoma cells (Hep3B) which lack the leukemia inhibitory factor receptor, CNTF was not able to induce acute-phase protein synthesis, indicating that this receptor protein may be part of the functional CNTF receptor on hepatic cells.", "contents": "Ciliary neurotrophic factor induces acute-phase protein expression in hepatocytes. During inflammatory states, hepatocytes are induced to synthesize and secrete a group of proteins called acute-phase proteins. It has recently been shown that besides interleukin-6 (IL-6), related cytokines such as leukemia inhibitory factor, oncostation M and interleukin-11 are also mediators of the hepatic acute-phase response. All these mediators belong to the hematopoietic family of alpha-helical cytokines. Here we show that an additional member of this cytokine family, ciliary neurotrophic factor (CNTF), induces the hepatic acute-phase protein genes haptoglobin, alpha 1-antichymotrypsin, alpha 2-macroglobulin and beta-fibrinogen in human hepatoma cells (HepG2) and in primary rat hepatocytes with a time course and dose-response comparable with that of IL-6. Our next aim was to define the receptor components used by CNTF on hepatic cells. Using a cell-free binding assay we exclude that CNTF binds to the 80 kDa IL-6 receptor, a protein with significant homology to the CNTF receptor which has recently been cloned from neuroblastoma cells. In human hepatoma cells (Hep3B) which lack the leukemia inhibitory factor receptor, CNTF was not able to induce acute-phase protein synthesis, indicating that this receptor protein may be part of the functional CNTF receptor on hepatic cells."} {"id": "PMID:1281790", "title": "Molecular cloning of a novel protein-tyrosine phosphatase SH-PTP3 with sequence similarity to the src-homology region 2.", "content": "Protein-tyrosine phosphorylation and dephosphorylation are directly associated with cellular growth, signal transduction, and neoplastic transformation. Here we report the isolation of a complementary DNA (cDNA) clone encoding a novel protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 68-kDa protein composed of 593 amino acids which contains two src-homology region 2's (SH2 domains) at the N terminus; this PTP is designated as SH-PTP3. Northern blot analysis revealed that SH-PTP3 mRNA was expressed throughout many tissues and the transcriptional size was consistent at about 6.0 kb. As with other SH2 domains in src-family kinases, the SH2 domains of SH-PTP3 may play a crucial role in interactions with tyrosine phosphorylated signaling proteins, including itself and protein tyrosine kinases (PTKs), to regulate targets' enzyme activity.", "contents": "Molecular cloning of a novel protein-tyrosine phosphatase SH-PTP3 with sequence similarity to the src-homology region 2. Protein-tyrosine phosphorylation and dephosphorylation are directly associated with cellular growth, signal transduction, and neoplastic transformation. Here we report the isolation of a complementary DNA (cDNA) clone encoding a novel protein-tyrosine phosphatase (PTP) from a human T cell PEER cDNA library. The predicted open reading frame encodes a approximately 68-kDa protein composed of 593 amino acids which contains two src-homology region 2's (SH2 domains) at the N terminus; this PTP is designated as SH-PTP3. Northern blot analysis revealed that SH-PTP3 mRNA was expressed throughout many tissues and the transcriptional size was consistent at about 6.0 kb. As with other SH2 domains in src-family kinases, the SH2 domains of SH-PTP3 may play a crucial role in interactions with tyrosine phosphorylated signaling proteins, including itself and protein tyrosine kinases (PTKs), to regulate targets' enzyme activity."} {"id": "PMID:1281791", "title": "Tumor necrosis factor modulation of expression of the cystic fibrosis transmembrane conductance regulator gene.", "content": "Based on the knowledge that expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can be modulated at the transcriptional level, and that the CFTR gene promoter contains sequences homologous to elements in other promoters that respond to tumor necrosis factor-alpha (TNF), we evaluated the hypothesis that TNF might modulate CFTR gene expression in epithelial cells. Studies with HT-29 cells, a colon epithelium-derived tumor cell line known to express the CFTR gene, demonstrated that TNF downregulated CFTR mRNA transcript levels in a dose- and time-dependent fashion. Interestingly, nuclear run-on analyses demonstrated that TNF did not affect the rate of transcription of CFTR gene, but exposure of the cells to TNF did modify the stability of CFTR mRNA transcripts, resulting in a mRNA half-life that was reduced to 65% of the resting level. These observations suggest that CFTR gene expression can be modulated by TNF, at least in part, at the posttranscriptional level.", "contents": "Tumor necrosis factor modulation of expression of the cystic fibrosis transmembrane conductance regulator gene. Based on the knowledge that expression of the cystic fibrosis transmembrane conductance regulator (CFTR) gene can be modulated at the transcriptional level, and that the CFTR gene promoter contains sequences homologous to elements in other promoters that respond to tumor necrosis factor-alpha (TNF), we evaluated the hypothesis that TNF might modulate CFTR gene expression in epithelial cells. Studies with HT-29 cells, a colon epithelium-derived tumor cell line known to express the CFTR gene, demonstrated that TNF downregulated CFTR mRNA transcript levels in a dose- and time-dependent fashion. Interestingly, nuclear run-on analyses demonstrated that TNF did not affect the rate of transcription of CFTR gene, but exposure of the cells to TNF did modify the stability of CFTR mRNA transcripts, resulting in a mRNA half-life that was reduced to 65% of the resting level. These observations suggest that CFTR gene expression can be modulated by TNF, at least in part, at the posttranscriptional level."} {"id": "PMID:1281792", "title": "A 25 kDa alpha 2-microglobulin-related protein is a component of the 125 kDa form of human gelatinase.", "content": "Besides the monomeric mammalian 95 kDa progelatinase, two additional forms, a disulfide-bridged 220 kDa dimer and a 125 kDa form were isolated from human PMN leukocytes. The 125 kDa progelatinase was identified as a covalently linked, disulfide-bridged heterodimer formed of the monomer with a 25 kDa protein. This 25 kDa protein was isolated from gelatinase bound to the affinity support of gelatin-Sepharose and eluted by DTE-containing buffer. The amino acid sequence of tryptic peptides of this protein revealed homology with an alpha 2-microglobulin-related protein from rats, a protein so far unknown in humans.", "contents": "A 25 kDa alpha 2-microglobulin-related protein is a component of the 125 kDa form of human gelatinase. Besides the monomeric mammalian 95 kDa progelatinase, two additional forms, a disulfide-bridged 220 kDa dimer and a 125 kDa form were isolated from human PMN leukocytes. The 125 kDa progelatinase was identified as a covalently linked, disulfide-bridged heterodimer formed of the monomer with a 25 kDa protein. This 25 kDa protein was isolated from gelatinase bound to the affinity support of gelatin-Sepharose and eluted by DTE-containing buffer. The amino acid sequence of tryptic peptides of this protein revealed homology with an alpha 2-microglobulin-related protein from rats, a protein so far unknown in humans."} {"id": "PMID:1281793", "title": "Side chain and backbone assignments in isotopically labeled proteins from two heteronuclear triple resonance experiments.", "content": "Two multi-dimensional heteronuclear NMR experiments are described for assigning the resonances in uniformly 15N- and 13C-labeled proteins. In one experiment (HCNH-TOCSY), the amide nitrogen and proton are correlated to the side-chain protons and carbons of the same and preceding residue. In a second triple resonance experiment (HC(CO)NH-TOCSY), the amide nitrogen and proton of one residue is correlated exclusively with the side-chain proton and carbon resonances of the preceding residue by transferring magnetization through the intervening carbonyl. The utility of these two experiments for making sequential resonance assignments in proteins is illustrated for [U-15N,13C]FKBP (107 residues) complexed to the immunosuppressant, ascomycin.", "contents": "Side chain and backbone assignments in isotopically labeled proteins from two heteronuclear triple resonance experiments. Two multi-dimensional heteronuclear NMR experiments are described for assigning the resonances in uniformly 15N- and 13C-labeled proteins. In one experiment (HCNH-TOCSY), the amide nitrogen and proton are correlated to the side-chain protons and carbons of the same and preceding residue. In a second triple resonance experiment (HC(CO)NH-TOCSY), the amide nitrogen and proton of one residue is correlated exclusively with the side-chain proton and carbon resonances of the preceding residue by transferring magnetization through the intervening carbonyl. The utility of these two experiments for making sequential resonance assignments in proteins is illustrated for [U-15N,13C]FKBP (107 residues) complexed to the immunosuppressant, ascomycin."} {"id": "PMID:1281794", "title": "Secondary structure of human granulocyte colony-stimulating factor derived from NMR spectroscopy.", "content": "Recombinant 15N-, 13C-labeled human granulocyte colony-stimulating factor (rh-metG-CSF) has been studied by 2D and 3D NMR using uniformly labeled protein as well as residue-specific 15N-labeled samples. Assignment of the 1H, 15N backbone, and 60% 1H sidechain resonances has enabled the determination of the secondary structure of the protein. The secondary structure is dominated by alpha-helical regions with four stretches of helices between residues 11-41, 71-95, 102-124 and 144-170.", "contents": "Secondary structure of human granulocyte colony-stimulating factor derived from NMR spectroscopy. Recombinant 15N-, 13C-labeled human granulocyte colony-stimulating factor (rh-metG-CSF) has been studied by 2D and 3D NMR using uniformly labeled protein as well as residue-specific 15N-labeled samples. Assignment of the 1H, 15N backbone, and 60% 1H sidechain resonances has enabled the determination of the secondary structure of the protein. The secondary structure is dominated by alpha-helical regions with four stretches of helices between residues 11-41, 71-95, 102-124 and 144-170."} {"id": "PMID:1281795", "title": "[Sex steroid hormones and brain serotonin in the estrous cycle of silver foxes].", "content": "A significant increase in hypothalamic serotonin and estradiol levels was found in silver foxes during proestrus. During estrus, the plasma estradiol concentration was reduced and a significant increase in progesterone level was correlated with a decrease in the brain serotonin content. The data obtained suggest that the brain serotonin plays a mediating role in the control of ovarian hormonal activity and ovulation in silver foxes.", "contents": "[Sex steroid hormones and brain serotonin in the estrous cycle of silver foxes]. A significant increase in hypothalamic serotonin and estradiol levels was found in silver foxes during proestrus. During estrus, the plasma estradiol concentration was reduced and a significant increase in progesterone level was correlated with a decrease in the brain serotonin content. The data obtained suggest that the brain serotonin plays a mediating role in the control of ovarian hormonal activity and ovulation in silver foxes."} {"id": "PMID:1281796", "title": "[The nature of the changes in the content of regulatory peptides in the pulmonary vascular bed].", "content": "The data obtained in white rats and dogs' isolated lungs showed the blood level of peptides to fluctuate within 30-50% of the total peptides concentration in blood. The process is cyclic, its rhythm not depending on the peptides level in venous blood.", "contents": "[The nature of the changes in the content of regulatory peptides in the pulmonary vascular bed]. The data obtained in white rats and dogs' isolated lungs showed the blood level of peptides to fluctuate within 30-50% of the total peptides concentration in blood. The process is cyclic, its rhythm not depending on the peptides level in venous blood."} {"id": "PMID:1281797", "title": "[Immune regulation of ovarian function].", "content": "Although it is well established that the pituitary gonadotropins and prolactin are the primary regulators of ovarian function, steroidal and nonsteroidal molecules produced locally in the ovary have been implicated in the modulation of gonadotropin action as autocrine or paracrine regulators. Recent studies suggest that the cells of the immune system play important roles in regulating ovarian function, and the immune regulation of ovarian function has become one of the topics in the field of ovarian physiology. Since it has become clear that the immune factors, cytokines, show a wide range of biological functions, not only on immune cells but also on nonimmune cells, the physiological significance of the resident immune cells, the widespread distribution of which in mammalian ovaries has been known for a long time, has reattracted attention as a third kind of regulator of ovarian function. In this article, current knowledge of the regulatory roles of immune cells as well as the cytokines in ovarian physiology is reviewed.", "contents": "[Immune regulation of ovarian function]. Although it is well established that the pituitary gonadotropins and prolactin are the primary regulators of ovarian function, steroidal and nonsteroidal molecules produced locally in the ovary have been implicated in the modulation of gonadotropin action as autocrine or paracrine regulators. Recent studies suggest that the cells of the immune system play important roles in regulating ovarian function, and the immune regulation of ovarian function has become one of the topics in the field of ovarian physiology. Since it has become clear that the immune factors, cytokines, show a wide range of biological functions, not only on immune cells but also on nonimmune cells, the physiological significance of the resident immune cells, the widespread distribution of which in mammalian ovaries has been known for a long time, has reattracted attention as a third kind of regulator of ovarian function. In this article, current knowledge of the regulatory roles of immune cells as well as the cytokines in ovarian physiology is reviewed."} {"id": "PMID:1281798", "title": "Acinar cell carcinoma of the pancreas with elevated serum alpha-fetoprotein levels: a case report and a review of 28 cases reported in Japan.", "content": "A 60-year-old male with elevated serum AFP levels is reported. Other tumor markers apart from AFP were normal. Serum AFP did not bind to Con A or Lentil-lectin by affinity chromatography. Abdominal ultrasonography, computed tomography and endoscopic retrograded cholangiopancreatography demonstrated a tumor extending from the body to the tail of the pancreas. The tumor was strongly suggested to be an acinar cell carcinoma of the pancreas, based on the histological findings of the resected specimen. The peroxidase-antiperoxidase method showed cancer cells to be positive for AFP. In Japan, only 27 cases of pancreatic cancer with elevated serum AFP level have been reported. This is the first Japanese case of pancreatic cancer in which the binding of serum AFP to lectins was investigated.", "contents": "Acinar cell carcinoma of the pancreas with elevated serum alpha-fetoprotein levels: a case report and a review of 28 cases reported in Japan. A 60-year-old male with elevated serum AFP levels is reported. Other tumor markers apart from AFP were normal. Serum AFP did not bind to Con A or Lentil-lectin by affinity chromatography. Abdominal ultrasonography, computed tomography and endoscopic retrograded cholangiopancreatography demonstrated a tumor extending from the body to the tail of the pancreas. The tumor was strongly suggested to be an acinar cell carcinoma of the pancreas, based on the histological findings of the resected specimen. The peroxidase-antiperoxidase method showed cancer cells to be positive for AFP. In Japan, only 27 cases of pancreatic cancer with elevated serum AFP level have been reported. This is the first Japanese case of pancreatic cancer in which the binding of serum AFP to lectins was investigated."} {"id": "PMID:1281800", "title": "Identification and characterization of a cross-reactive and a unique B-cell epitope on the hsp60 homologue from Neisseria gonorrhoeae.", "content": "Two monoclonal antibodies (G6 and 7B), generated against a 63-kDa stress protein (GSP63) from Neisseria gonorrhoeae strain VP1, were used to investigate the antigenic heterogeneity of GSP63 among the Neisseriaceae and its antigenic relationship with the Hsp60 heat-shock protein family. Immunoblotting experiments demonstrated antibody reactivity with all pathogenic Neisseria tested and with some of the commensal strains. One of the antibodies (7B) cross-reacted with the 65-kDa M. bovis BCG heat-shock protein and with 14 out of the 21 similarly sized proteins in other bacterial species. The other antibody (G6) specifically recognized neisserial GSP63 homologues. These results demonstrate that GSP63 is a conserved neisserial antigen bearing both a unique neisserial B-cell epitope and a more widely distributed Hsp60 epitope.", "contents": "Identification and characterization of a cross-reactive and a unique B-cell epitope on the hsp60 homologue from Neisseria gonorrhoeae. Two monoclonal antibodies (G6 and 7B), generated against a 63-kDa stress protein (GSP63) from Neisseria gonorrhoeae strain VP1, were used to investigate the antigenic heterogeneity of GSP63 among the Neisseriaceae and its antigenic relationship with the Hsp60 heat-shock protein family. Immunoblotting experiments demonstrated antibody reactivity with all pathogenic Neisseria tested and with some of the commensal strains. One of the antibodies (7B) cross-reacted with the 65-kDa M. bovis BCG heat-shock protein and with 14 out of the 21 similarly sized proteins in other bacterial species. The other antibody (G6) specifically recognized neisserial GSP63 homologues. These results demonstrate that GSP63 is a conserved neisserial antigen bearing both a unique neisserial B-cell epitope and a more widely distributed Hsp60 epitope."} {"id": "PMID:1281801", "title": "I elements and the Drosophila genome.", "content": "LINEs are a large class of transposable elements in eukaryotes. They transpose by reverse transcription of an RNA intermediate. I elements of Drosophila melanogaster belong to this class and are responsible for the I-R system of hybrid dysgenesis. Many results indicate that at the beginning of the century natural populations of this species were devoid of active I elements and that they were invaded by functional I elements in the last decades. Many Drosophila species contain both defective and active I elements. It seems that the latter were lost in Drosophila melanogaster before its spread throughout the world, and that the recent invasion results from the spread of functional elements originating either from another species by horizontal transfer or from an isolated population of the same species. These data are discussed, as well as their significance in evolutionary processes.", "contents": "I elements and the Drosophila genome. LINEs are a large class of transposable elements in eukaryotes. They transpose by reverse transcription of an RNA intermediate. I elements of Drosophila melanogaster belong to this class and are responsible for the I-R system of hybrid dysgenesis. Many results indicate that at the beginning of the century natural populations of this species were devoid of active I elements and that they were invaded by functional I elements in the last decades. Many Drosophila species contain both defective and active I elements. It seems that the latter were lost in Drosophila melanogaster before its spread throughout the world, and that the recent invasion results from the spread of functional elements originating either from another species by horizontal transfer or from an isolated population of the same species. These data are discussed, as well as their significance in evolutionary processes."} {"id": "PMID:1281802", "title": "Retrotransposons and the evolution of mammalian gene expression.", "content": "Transposable elements, and retroviral-like elements in particular, are a rich potential source of genetic variation within a host's genome. Many mutations of endogenous genes in phylogenetically diverse organisms are due to insertion of elements that affect gene expression by altering the normal pattern of regulation. While few such associations are known to have been maintained over time, two recently elucidated examples suggest transposable elements may have a significant impact in evolution of gene expression. The first example, concerning the mouse sex-limited protein (Slp), clearly establishes that ancient retroviral enhancer sequences now confer hormonal dependence on the adjacent gene. The second example shows that within the human amylase gene family, salivary specific expression has arisen due to inserted sequences, deriving perhaps from a conjunction of two retrotransposable elements.", "contents": "Retrotransposons and the evolution of mammalian gene expression. Transposable elements, and retroviral-like elements in particular, are a rich potential source of genetic variation within a host's genome. Many mutations of endogenous genes in phylogenetically diverse organisms are due to insertion of elements that affect gene expression by altering the normal pattern of regulation. While few such associations are known to have been maintained over time, two recently elucidated examples suggest transposable elements may have a significant impact in evolution of gene expression. The first example, concerning the mouse sex-limited protein (Slp), clearly establishes that ancient retroviral enhancer sequences now confer hormonal dependence on the adjacent gene. The second example shows that within the human amylase gene family, salivary specific expression has arisen due to inserted sequences, deriving perhaps from a conjunction of two retrotransposable elements."} {"id": "PMID:1281804", "title": "Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results.", "content": "Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens.", "contents": "Nondysgerminomatous tumors of the ovary treated with cisplatin, vinblastine, and bleomycin: long-term results. Twenty-four consecutive patients with nondysgerminomatous germ cell tumor of the ovary were treated after surgery with cisplatin, vinblastine, and bleomycin (PVB regimen). The cycle was repeated every 3 weeks for three to five courses. Fourteen patients had endodermal sinus tumor, and 10 had mixed germ cell tumors. Stage of disease (FIGO, 1986) was as follows: stage I, 6; stage IIc-IV, 17; and recurrence, 1 patient. All patients were monitored by alpha-fetoprotein and human chorionic gonadotropin. Only 1 patient had received previous chemotherapy. All 5 patients without residual disease and with negative marker levels in which PVB was used as adjuvant treatment were free of disease for a median duration of 59 months from the start of PVB. Of the 19 patients with measurable disease (evident disease or positive marker levels), complete remission was obtained in 16 (84%), but 5 of these relapsed. Therefore, treatment with PVB failed in 8 out of 19 patients (42%) with measurable disease. Toxicity was evident, but no patient died of it. Menses were regular in 11 patients whose initial surgery was conservative. PVB regimen is an effective but not a satisfactory treatment. The considerable failure rate of PVB treatment suggests the investigation of other regimens."} {"id": "PMID:1281805", "title": "Tissue reactivity of anti-Leu19.", "content": "Monoclonal antibody anti-Leu19, is a marker of natural killer cells. Since reactivity between anti-Leu7, another natural killer cell marker, and small cell neuroendocrine carcinomas has been described, we evaluated the reactivity of anti-Leu19 in 92 neuroendocrine tumours. Frozen sections in each case were immunostained using the avidin-biotin-peroxidase complex method with monoclonal anti-Leu19. We found Leu19 expression in 93% of the cases. We also evaluated 149 other tumours, including adenocarcinomas, undifferentiated large cell carcinomas, lymphomas, melanomas and soft tissue tumours. We found Leu19 expression in 36% (by liberal interpretative criteria), or 29% (by conservative interpretative criteria) of these cases. Thus, while anti-Leu19 appears to be a sensitive marker for neuroendocrine tumours, a lack of specificity limits its practical application in diagnostic histopathology.", "contents": "Tissue reactivity of anti-Leu19. Monoclonal antibody anti-Leu19, is a marker of natural killer cells. Since reactivity between anti-Leu7, another natural killer cell marker, and small cell neuroendocrine carcinomas has been described, we evaluated the reactivity of anti-Leu19 in 92 neuroendocrine tumours. Frozen sections in each case were immunostained using the avidin-biotin-peroxidase complex method with monoclonal anti-Leu19. We found Leu19 expression in 93% of the cases. We also evaluated 149 other tumours, including adenocarcinomas, undifferentiated large cell carcinomas, lymphomas, melanomas and soft tissue tumours. We found Leu19 expression in 36% (by liberal interpretative criteria), or 29% (by conservative interpretative criteria) of these cases. Thus, while anti-Leu19 appears to be a sensitive marker for neuroendocrine tumours, a lack of specificity limits its practical application in diagnostic histopathology."} {"id": "PMID:1281806", "title": "Acidic mucin in the prostate: can it differentiate adenosis from adenocarcinoma?", "content": "Numerous reports have claimed that because acidic mucin is absent in benign prostatic glands and is present in some prostatic adenocarcinomas, this stain may be an adjunctive aid in the diagnosis of adenocarcinoma of the prostate. However, adenosis that mimics low-grade adenocarcinoma has not been evaluated to date. We studied 28 foci of adenosis for the presence of high iron diamine-alcian blue (HID-AB). Fifteen foci of adenosis (54%) showed strong staining for HID-AB; staining was diffuse in 11 cases and focal in four cases. An additional two cases (7%) showed equivocal staining. The remaining 11 cases (39%) lacked positivity. All cases of adenosis were verified with immunohistochemistry for keratin 903, a basal cell-specific antibody. This study demonstrates the limited use of acid mucin staining in the diagnosis of adenocarcinoma. The finding of HID-AB positivity in occasional isolated benign small prostatic glands within hyperplastic nodules suggests that acid mucin secretion may be a reflection of gland size or proliferation rather than evidence that adenosis is related to adenocarcinoma of the prostate.", "contents": "Acidic mucin in the prostate: can it differentiate adenosis from adenocarcinoma? Numerous reports have claimed that because acidic mucin is absent in benign prostatic glands and is present in some prostatic adenocarcinomas, this stain may be an adjunctive aid in the diagnosis of adenocarcinoma of the prostate. However, adenosis that mimics low-grade adenocarcinoma has not been evaluated to date. We studied 28 foci of adenosis for the presence of high iron diamine-alcian blue (HID-AB). Fifteen foci of adenosis (54%) showed strong staining for HID-AB; staining was diffuse in 11 cases and focal in four cases. An additional two cases (7%) showed equivocal staining. The remaining 11 cases (39%) lacked positivity. All cases of adenosis were verified with immunohistochemistry for keratin 903, a basal cell-specific antibody. This study demonstrates the limited use of acid mucin staining in the diagnosis of adenocarcinoma. The finding of HID-AB positivity in occasional isolated benign small prostatic glands within hyperplastic nodules suggests that acid mucin secretion may be a reflection of gland size or proliferation rather than evidence that adenosis is related to adenocarcinoma of the prostate."} {"id": "PMID:1281807", "title": "Efficacy and safety of sotalol in patients with complex ventricular arrhythmias.", "content": "Sotalol is a unique beta-blocker that prolongs repolarization. Its use in 626 patients with complex ventricular ectopic activity, as reported in the literature, resulted in suppression of arrhythmia in 50 to 60% of treatment attempts. Detailed analysis of data on arrhythmias in 356 patients that were entered prospectively into a database revealed a median reduction in ventricular premature beats of 76%, compared to a median suppression of repetitive ventricular ectopic activity of 91% and of episodes of nonsustained ventricular tachycardia of 97% (p = 0.002 vs reduction of ventricular premature beats). This marked antiarrhythmic potency of sotalol in repetitive ventricular arrhythmias is thought to be due to its class III activity. Drug efficacy was independent of age, sex, the presence or absence of organic heart disease and the degree of sotalol-induced prolongation of corrected QT interval. Evaluation of left ventricular function in 215 patients treated with the drug demonstrated that depression of left ventricular ejection fraction occurred far less frequently than expected with conventional beta-blockers. Even patients with severely depressed pump function tolerated sotalol surprisingly well. There is a propensity of the drug to aggravate arrhythmia, which resulted in serious proarrhythmic events in 30 (3.5%) of 853 patients. These often consisted of torsades de pointes (9 of 30 patients). Proarrhythmia occurred primarily within the first 3 days of dosing, and exhibited a dose-dependence. In conclusion, sotalol is an effective and well-tolerated antiarrhythmic drug in patients with complex ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Efficacy and safety of sotalol in patients with complex ventricular arrhythmias. Sotalol is a unique beta-blocker that prolongs repolarization. Its use in 626 patients with complex ventricular ectopic activity, as reported in the literature, resulted in suppression of arrhythmia in 50 to 60% of treatment attempts. Detailed analysis of data on arrhythmias in 356 patients that were entered prospectively into a database revealed a median reduction in ventricular premature beats of 76%, compared to a median suppression of repetitive ventricular ectopic activity of 91% and of episodes of nonsustained ventricular tachycardia of 97% (p = 0.002 vs reduction of ventricular premature beats). This marked antiarrhythmic potency of sotalol in repetitive ventricular arrhythmias is thought to be due to its class III activity. Drug efficacy was independent of age, sex, the presence or absence of organic heart disease and the degree of sotalol-induced prolongation of corrected QT interval. Evaluation of left ventricular function in 215 patients treated with the drug demonstrated that depression of left ventricular ejection fraction occurred far less frequently than expected with conventional beta-blockers. Even patients with severely depressed pump function tolerated sotalol surprisingly well. There is a propensity of the drug to aggravate arrhythmia, which resulted in serious proarrhythmic events in 30 (3.5%) of 853 patients. These often consisted of torsades de pointes (9 of 30 patients). Proarrhythmia occurred primarily within the first 3 days of dosing, and exhibited a dose-dependence. In conclusion, sotalol is an effective and well-tolerated antiarrhythmic drug in patients with complex ventricular ectopic activity.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281808", "title": "A 2-year prospective study of very low birthweight infants.", "content": "A prospective 2-year follow-up study was carried out on 68 of the 69 surviving very low birthweight (VLBW) infants (< 1,501 g) born in Bikur Holim Hospital in the years 1985-87. The aims were a) to determine the incidence of major disability, and b) to compare the 2-year outcome of VLBW infants without major disability with that of a control group of full-term small-for-gestational-age infants, using the Mental Development Index (MDI) of the Bayley Scales. Mean birthweight of the VLBW infants was 1,234 +/- 216 g and mean gestational age was 30.7 +/- 2.4 weeks. Their neonatal mortality during the study period was 29.8%. Major disability was diagnosed in 11/68 infants (16%). At age 2 years there was no significant difference between the mean MDI of the VLBW infants without major disability (97.7 +/- 19.5) and that of the controls (99.7 +/- 17.0). These data, representing the outcome of VLBW infants from a community-based hospital with neonatal intensive care facilities, are comparable in incidence of major disability with data of large tertiary centers. Cognitive ability of VLBW infants without major disability at age 2 years was equivalent to that of their full-term peers.", "contents": "A 2-year prospective study of very low birthweight infants. A prospective 2-year follow-up study was carried out on 68 of the 69 surviving very low birthweight (VLBW) infants (< 1,501 g) born in Bikur Holim Hospital in the years 1985-87. The aims were a) to determine the incidence of major disability, and b) to compare the 2-year outcome of VLBW infants without major disability with that of a control group of full-term small-for-gestational-age infants, using the Mental Development Index (MDI) of the Bayley Scales. Mean birthweight of the VLBW infants was 1,234 +/- 216 g and mean gestational age was 30.7 +/- 2.4 weeks. Their neonatal mortality during the study period was 29.8%. Major disability was diagnosed in 11/68 infants (16%). At age 2 years there was no significant difference between the mean MDI of the VLBW infants without major disability (97.7 +/- 19.5) and that of the controls (99.7 +/- 17.0). These data, representing the outcome of VLBW infants from a community-based hospital with neonatal intensive care facilities, are comparable in incidence of major disability with data of large tertiary centers. Cognitive ability of VLBW infants without major disability at age 2 years was equivalent to that of their full-term peers."} {"id": "PMID:1281810", "title": "[Granulocyte colony stimulating factor (G-CSF) in treatment of patients with HIV-associated mucocutaneous Kaposi sarcoma. Successful use in virus and drug-induced leukopenia].", "content": "Three patients with HIV-associated Kaposi sarcoma were treated with human recombinant granulocyte colony stimulating factor (G-CSF). They had all developed leucopenia during treatment with recombinant interferon-alpha-2a, in two cases combined with vincristine. In all three patients, there was an obvious rapid stimulation after s.c. injection of 300 or 150 micrograms G-CSF per day; the white blood count reached normal values within only a few days and partial transformation to leucocytosis took place. After discontinuation of G-CSF, leucocyte counts regressed rapidly to pretreatment levels. A dose of 150 micrograms of G-CSF twice to three times per week proved to be sufficient to keep the white blood cell count in the normal range allowing the treatment necessary for Kaposi sarcoma. G-CSF therapy had no serious side effects. One of the patients developed a tumour-like infiltration in his left upper jaw, which histologically simulated Burkitt's lymphoma and which regressed spontaneously after discontinuation of the G-CSF therapy. G-CSF plays an important role in the treatment of patients with HIV-associated Kaposi sarcoma and enables combined treatment with zidovudine, interferon, and cytostatic drugs.", "contents": "[Granulocyte colony stimulating factor (G-CSF) in treatment of patients with HIV-associated mucocutaneous Kaposi sarcoma. Successful use in virus and drug-induced leukopenia]. Three patients with HIV-associated Kaposi sarcoma were treated with human recombinant granulocyte colony stimulating factor (G-CSF). They had all developed leucopenia during treatment with recombinant interferon-alpha-2a, in two cases combined with vincristine. In all three patients, there was an obvious rapid stimulation after s.c. injection of 300 or 150 micrograms G-CSF per day; the white blood count reached normal values within only a few days and partial transformation to leucocytosis took place. After discontinuation of G-CSF, leucocyte counts regressed rapidly to pretreatment levels. A dose of 150 micrograms of G-CSF twice to three times per week proved to be sufficient to keep the white blood cell count in the normal range allowing the treatment necessary for Kaposi sarcoma. G-CSF therapy had no serious side effects. One of the patients developed a tumour-like infiltration in his left upper jaw, which histologically simulated Burkitt's lymphoma and which regressed spontaneously after discontinuation of the G-CSF therapy. G-CSF plays an important role in the treatment of patients with HIV-associated Kaposi sarcoma and enables combined treatment with zidovudine, interferon, and cytostatic drugs."} {"id": "PMID:1281811", "title": "[Scabies norvegica sive crustosa in a patient with AIDS].", "content": "We report the case of a 20-year-old homosexual man with HIV-1 infection presenting with AIDS. An erythemato-squamous, papulo-crustous, non-itching dermatosis of 4 months duration was finally diagnosed as Norwegian scabies in the immunosuppressed. For clinical and epidemiological reasons the high contagiosity of this rare entity requires an appropriate therapy without delay.", "contents": "[Scabies norvegica sive crustosa in a patient with AIDS]. We report the case of a 20-year-old homosexual man with HIV-1 infection presenting with AIDS. An erythemato-squamous, papulo-crustous, non-itching dermatosis of 4 months duration was finally diagnosed as Norwegian scabies in the immunosuppressed. For clinical and epidemiological reasons the high contagiosity of this rare entity requires an appropriate therapy without delay."} {"id": "PMID:1281812", "title": "[Angioimmunoblastic lymphadenopathy with cutaneous manifestations in a 13-year-old girl].", "content": "We describe a 13-year-old girl with angioimmunoblastic lymphadenopathy. The patient's main symptom was a generalized pruritic maculopapular rash located mainly on the upper and lower limbs. In addition to the skin lesions, physical examination revealed enlarged cervical, axillary and inguinal lymph nodes. There were also hepatosplenomegaly and oedema of both hands. Blood examination showed elevated ESR, haemolytic anaemia, polyclonal hypergammaglobulinaemia and eosinophilia. Virus serology including HIV I and II and HTLV I was negative. Histopathological examination of a lesional skin biopsy showed superficial and deep dermal infiltrate extending into the subcutaneous tissue. The infiltrate consisted of lymphocytes, some with atypical nuclei, histiocytoid cells, and few eosinophils. There was also proliferation of dermal blood vessels. Examination of an enlarged cervical lymph node disclosed typical histopathological features of angioimmunoblastic lymphadenopathy and confirmed the diagnosis.", "contents": "[Angioimmunoblastic lymphadenopathy with cutaneous manifestations in a 13-year-old girl]. We describe a 13-year-old girl with angioimmunoblastic lymphadenopathy. The patient's main symptom was a generalized pruritic maculopapular rash located mainly on the upper and lower limbs. In addition to the skin lesions, physical examination revealed enlarged cervical, axillary and inguinal lymph nodes. There were also hepatosplenomegaly and oedema of both hands. Blood examination showed elevated ESR, haemolytic anaemia, polyclonal hypergammaglobulinaemia and eosinophilia. Virus serology including HIV I and II and HTLV I was negative. Histopathological examination of a lesional skin biopsy showed superficial and deep dermal infiltrate extending into the subcutaneous tissue. The infiltrate consisted of lymphocytes, some with atypical nuclei, histiocytoid cells, and few eosinophils. There was also proliferation of dermal blood vessels. Examination of an enlarged cervical lymph node disclosed typical histopathological features of angioimmunoblastic lymphadenopathy and confirmed the diagnosis."} {"id": "PMID:1281814", "title": "Burn nursing Delphi study: pain management.", "content": "In 1989 a Delphi study was undertaken to identify the nursing priorities in burn research. The Delphi technique is a series of questionnaires used to reach consensus. Ninety-four nurses involved in burn care completed four rounds of questionnaires containing 101 research questions. This, the seventh and final report, concerns a significant area of burn research, which is pain management. Eleven (10%) of the 101 questions dealt with pain, whereas five were rated among the top 20 priority questions. As a category the questions concerning pain management had a mean score of 5.91 on a 0 to 7 Likert scale. The questions collectively were cited as having the most impact on the welfare of the patient with burns.", "contents": "Burn nursing Delphi study: pain management. In 1989 a Delphi study was undertaken to identify the nursing priorities in burn research. The Delphi technique is a series of questionnaires used to reach consensus. Ninety-four nurses involved in burn care completed four rounds of questionnaires containing 101 research questions. This, the seventh and final report, concerns a significant area of burn research, which is pain management. Eleven (10%) of the 101 questions dealt with pain, whereas five were rated among the top 20 priority questions. As a category the questions concerning pain management had a mean score of 5.91 on a 0 to 7 Likert scale. The questions collectively were cited as having the most impact on the welfare of the patient with burns."} {"id": "PMID:1281815", "title": "The single transmembrane segment of gp210 is sufficient for sorting to the pore membrane domain of the nuclear envelope.", "content": "The glycoprotein gp210 is located in the \"pore membrane,\" a specialized domain of the nuclear envelope to which the nuclear pore complex (NPC) is anchored. gp210 contains a large cisternal domain, a single transmembrane segment (TM), and a COOH-terminal, 58-amino acid residue cytoplasmic tail (CT) (Wozniak, R. W., E. Bartnik, and G. Blobel. 1989. J. Cell Biol. 108:2083-2092; Greber, U. F., A. Senior, and L. Gerace. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:1495-1502). To locate determinants for sorting of gp210 to the pore membrane, we constructed various cDNAs coding for wild-type, mutant, and chimeric gp210, and monitored localization of the expressed protein in 3T3 cells by immunofluorescence microscopy using appropriate antibodies. The large cisternal domain of gp210 (95% of its mass) did not reveal any sorting determinants. Surprisingly, the TM of gp210 is sufficient for sorting to the pore membrane. The CT also contains a sorting determinant, but it is weaker than that of the TM. We propose specific lateral association of the transmembrane helices of two proteins to yield either a gp210 homodimer or a heterodimer of gp210 and another protein. The cytoplasmically oriented tails of these dimers may bind cooperatively to the adjacent NPCs. In addition, we demonstrate that gp210 co-localizes with cytoplasmically dispersed nucleoporins, suggesting a cytoplasmic association of these components.", "contents": "The single transmembrane segment of gp210 is sufficient for sorting to the pore membrane domain of the nuclear envelope. The glycoprotein gp210 is located in the \"pore membrane,\" a specialized domain of the nuclear envelope to which the nuclear pore complex (NPC) is anchored. gp210 contains a large cisternal domain, a single transmembrane segment (TM), and a COOH-terminal, 58-amino acid residue cytoplasmic tail (CT) (Wozniak, R. W., E. Bartnik, and G. Blobel. 1989. J. Cell Biol. 108:2083-2092; Greber, U. F., A. Senior, and L. Gerace. 1990. EMBO (Eur. Mol. Biol. Organ.) J. 9:1495-1502). To locate determinants for sorting of gp210 to the pore membrane, we constructed various cDNAs coding for wild-type, mutant, and chimeric gp210, and monitored localization of the expressed protein in 3T3 cells by immunofluorescence microscopy using appropriate antibodies. The large cisternal domain of gp210 (95% of its mass) did not reveal any sorting determinants. Surprisingly, the TM of gp210 is sufficient for sorting to the pore membrane. The CT also contains a sorting determinant, but it is weaker than that of the TM. We propose specific lateral association of the transmembrane helices of two proteins to yield either a gp210 homodimer or a heterodimer of gp210 and another protein. The cytoplasmically oriented tails of these dimers may bind cooperatively to the adjacent NPCs. In addition, we demonstrate that gp210 co-localizes with cytoplasmically dispersed nucleoporins, suggesting a cytoplasmic association of these components."} {"id": "PMID:1281816", "title": "Polarity of flagellar assembly in Chlamydomonas.", "content": "During mating of the alga Chlamydomonas, two biflagellate cells fuse to form a single quadriflagellate cell that contains two nuclei and a common cytoplasm. We have used this cell fusion during mating to transfer unassembled flagellar components from the cytoplasm of one Chlamydomonas cell into that of another in order to study in vivo the polarity of flagellar assembly. In the first series of experiments, sites of tubulin addition onto elongating flagellar axonemes were determined. Donor cells that had two full-length flagella and were expressing an epitope-tagged alpha-tubulin construct were mated (fused) with recipient cells that had two half-length flagella. Outgrowth of the shorter pair of flagella followed, using a common pool of precursors that now included epitope-tagged tubulin, resulting in quadriflagellates with four full-length flagella. Immunofluorescence and immunoelectron microscopy using an antiepitope antibody showed that both the outer doublet and central pair microtubules of the recipient cells' flagellar axonemes elongate solely by addition of new subunits at their distal ends. In a separate series of experiments, the polarity of assembly of a class of axonemal microtubule-associated structures, the radial spokes, was determined. Wild-type donor cells that had two full-length, motile flagella were mated with paralyzed recipient cells that had two full-length, radial spokeless flagella. Within 90 min after cell fusion, the previously paralyzed flagella became motile. Immunofluorescence microscopy using specific antiradial spoke protein antisera showed that radial spoke proteins appeared first at the tips of spokeless axonemes and gradually assembled toward the bases. Together, these results suggest that both tubulin and radial spoke proteins are transported to the tip of the flagellum before their assembly into flagellar structure.", "contents": "Polarity of flagellar assembly in Chlamydomonas. During mating of the alga Chlamydomonas, two biflagellate cells fuse to form a single quadriflagellate cell that contains two nuclei and a common cytoplasm. We have used this cell fusion during mating to transfer unassembled flagellar components from the cytoplasm of one Chlamydomonas cell into that of another in order to study in vivo the polarity of flagellar assembly. In the first series of experiments, sites of tubulin addition onto elongating flagellar axonemes were determined. Donor cells that had two full-length flagella and were expressing an epitope-tagged alpha-tubulin construct were mated (fused) with recipient cells that had two half-length flagella. Outgrowth of the shorter pair of flagella followed, using a common pool of precursors that now included epitope-tagged tubulin, resulting in quadriflagellates with four full-length flagella. Immunofluorescence and immunoelectron microscopy using an antiepitope antibody showed that both the outer doublet and central pair microtubules of the recipient cells' flagellar axonemes elongate solely by addition of new subunits at their distal ends. In a separate series of experiments, the polarity of assembly of a class of axonemal microtubule-associated structures, the radial spokes, was determined. Wild-type donor cells that had two full-length, motile flagella were mated with paralyzed recipient cells that had two full-length, radial spokeless flagella. Within 90 min after cell fusion, the previously paralyzed flagella became motile. Immunofluorescence microscopy using specific antiradial spoke protein antisera showed that radial spoke proteins appeared first at the tips of spokeless axonemes and gradually assembled toward the bases. Together, these results suggest that both tubulin and radial spoke proteins are transported to the tip of the flagellum before their assembly into flagellar structure."} {"id": "PMID:1281817", "title": "Recombinant murine steel factor stimulates in vitro production of granulocyte-macrophage progenitor cells.", "content": "The ability of murine Steel factor to promote the in vitro production of granulocyte-macrophage progenitor cells (CFU-GM) was examined in short-term liquid cultures. Bone marrow from C57BL/6J or Sl/Sld mice was placed in culture for seven days with either Steel factor alone or in the presence of IL-3. CFU-GM responsive to GM-CSF, IL-3, and CSF-1 were measured in the input population and again after 3 or 7 days in culture. Steel factor alone increased the number of all CFU-GM types as early as 3 days after culture initiation, with further increases at day 7. This effect was potentiated by the addition of IL-3. Production of CFU-GM by C57BL/6J or Sl/Sld marrow was comparable except for enhanced production of CSF-1 responsive progenitors by Sl/Sld marrow. A recombinant Sld protein was also shown to be equivalent to the wild-type protein in its capacity to promote CFU-GM production from normal bone marrow.", "contents": "Recombinant murine steel factor stimulates in vitro production of granulocyte-macrophage progenitor cells. The ability of murine Steel factor to promote the in vitro production of granulocyte-macrophage progenitor cells (CFU-GM) was examined in short-term liquid cultures. Bone marrow from C57BL/6J or Sl/Sld mice was placed in culture for seven days with either Steel factor alone or in the presence of IL-3. CFU-GM responsive to GM-CSF, IL-3, and CSF-1 were measured in the input population and again after 3 or 7 days in culture. Steel factor alone increased the number of all CFU-GM types as early as 3 days after culture initiation, with further increases at day 7. This effect was potentiated by the addition of IL-3. Production of CFU-GM by C57BL/6J or Sl/Sld marrow was comparable except for enhanced production of CSF-1 responsive progenitors by Sl/Sld marrow. A recombinant Sld protein was also shown to be equivalent to the wild-type protein in its capacity to promote CFU-GM production from normal bone marrow."} {"id": "PMID:1281818", "title": "Influence of mitomycin C on endothelial monolayer regeneration in vitro.", "content": "This study examines the effect of Mitomycin C, a fungal toxin which inhibits DNA synthesis, on the regeneration of partially denuded large vessel endothelium in vitro. Monolayers of bovine pulmonary artery endothelial cells were treated with Mitomycin C prior to or immediately following partial denudation and were incubated in the continuing presence of Mitomycin C; the effects of this treatment on monolayer repair, cell proliferation, and other aspects of endothelial phenotype were monitored. Cell proliferation, DNA, RNA, and protein synthesis were all reduced in a dose dependent manner in treated cultures. Incubation with Mitomycin C for 48 h or longer resulted in reduced cell spreading, and rounding up and loss of cells from both intact and partially denuded cultures. Effects were less severe with lower doses and shorter incubation times. However, significant reductions in monolayer regeneration occurred within 8 h of incubation, sufficiently early to suggest that Mitomycin C may affect aspects of the regeneration process independent of cell proliferation. Polarization/spreading of cells at the denudation edge was monitored by fluorescence staining for golgi with C5-DMB-ceramide, and for centrioles with antibodies to tubulin. Centrioles and golgi rapidly reoriented to a location at the putative leading edge of control cultures. Mitomycin C treatment had no effect on centriole reorientation, but caused a significant delay in golgi localization. These results suggest that Mitomycin C inhibits endothelial monolayer regeneration by mechanisms independent of cell proliferation and DNA synthesis, perhaps by interfering with cell spreading or translocation at the wound edge.", "contents": "Influence of mitomycin C on endothelial monolayer regeneration in vitro. This study examines the effect of Mitomycin C, a fungal toxin which inhibits DNA synthesis, on the regeneration of partially denuded large vessel endothelium in vitro. Monolayers of bovine pulmonary artery endothelial cells were treated with Mitomycin C prior to or immediately following partial denudation and were incubated in the continuing presence of Mitomycin C; the effects of this treatment on monolayer repair, cell proliferation, and other aspects of endothelial phenotype were monitored. Cell proliferation, DNA, RNA, and protein synthesis were all reduced in a dose dependent manner in treated cultures. Incubation with Mitomycin C for 48 h or longer resulted in reduced cell spreading, and rounding up and loss of cells from both intact and partially denuded cultures. Effects were less severe with lower doses and shorter incubation times. However, significant reductions in monolayer regeneration occurred within 8 h of incubation, sufficiently early to suggest that Mitomycin C may affect aspects of the regeneration process independent of cell proliferation. Polarization/spreading of cells at the denudation edge was monitored by fluorescence staining for golgi with C5-DMB-ceramide, and for centrioles with antibodies to tubulin. Centrioles and golgi rapidly reoriented to a location at the putative leading edge of control cultures. Mitomycin C treatment had no effect on centriole reorientation, but caused a significant delay in golgi localization. These results suggest that Mitomycin C inhibits endothelial monolayer regeneration by mechanisms independent of cell proliferation and DNA synthesis, perhaps by interfering with cell spreading or translocation at the wound edge."} {"id": "PMID:1281819", "title": "Induction of an immune response through the idiotypic network with monoclonal anti-idiotype antibodies in the carcinoembryonic antigen system.", "content": "Anti-idiotype antibodies can mimic the conformational epitopes of the original antigen and act as antigen substitutes for vaccination and/or serological purposes. To investigate this possibility concerning the tumor marker carcinoembryonic antigen (CEA), BALB/c mice were immunized with the previously described anti-CEA monoclonal antibody (MAb) 5.D11 (AB1). After cell fusion, 15 stable cloned cell lines secreting anti-Ids (AB2) were obtained. Selected MAbs gave various degrees of inhibition (up to 100%) of the binding of 125I-labeled CEA to MAb 5.D11. Absence of reactivity of anti-Id MAbs with normal mouse IgG was first demonstrated by the fact that anti-Id MAbs were not absorbed by passage through a mouse IgG column, and second because they bound specifically to non-reduced MAb 5.D11 on Western blots. Anti-5.D11 MAbs did not inhibit binding to CEA of MAb 10.B9, another anti-CEA antibody obtained in the same fusion as 5.D11, or that of several anti-CEA MAbs reported in an international workshop, with the exception of two other anti-CEA MAbs, both directed against the GOLD IV epitope. When applied to an Id-anti-Id competitive radioimmunoassay, a sensitivity of 2 ng/ml of CEA was obtained, which is sufficient for monitoring circulating CEA in carcinoma patients. To verify that the anti-Id MAbs have the potential to be used as CEA vaccines, syngeneic BALB/c mice were immunized with these MAbs (AB2). Sera from immunized mice were demonstrated to contain AB3 antibodies recognizing the original antigen, CEA, both in enzyme immunoassay and by immunoperoxidase staining of human colon carcinoma. These results open the perspective of vaccination against colorectal carcinoma through the use of anti-idiotype antibodies as antigen substitutes.", "contents": "Induction of an immune response through the idiotypic network with monoclonal anti-idiotype antibodies in the carcinoembryonic antigen system. Anti-idiotype antibodies can mimic the conformational epitopes of the original antigen and act as antigen substitutes for vaccination and/or serological purposes. To investigate this possibility concerning the tumor marker carcinoembryonic antigen (CEA), BALB/c mice were immunized with the previously described anti-CEA monoclonal antibody (MAb) 5.D11 (AB1). After cell fusion, 15 stable cloned cell lines secreting anti-Ids (AB2) were obtained. Selected MAbs gave various degrees of inhibition (up to 100%) of the binding of 125I-labeled CEA to MAb 5.D11. Absence of reactivity of anti-Id MAbs with normal mouse IgG was first demonstrated by the fact that anti-Id MAbs were not absorbed by passage through a mouse IgG column, and second because they bound specifically to non-reduced MAb 5.D11 on Western blots. Anti-5.D11 MAbs did not inhibit binding to CEA of MAb 10.B9, another anti-CEA antibody obtained in the same fusion as 5.D11, or that of several anti-CEA MAbs reported in an international workshop, with the exception of two other anti-CEA MAbs, both directed against the GOLD IV epitope. When applied to an Id-anti-Id competitive radioimmunoassay, a sensitivity of 2 ng/ml of CEA was obtained, which is sufficient for monitoring circulating CEA in carcinoma patients. To verify that the anti-Id MAbs have the potential to be used as CEA vaccines, syngeneic BALB/c mice were immunized with these MAbs (AB2). Sera from immunized mice were demonstrated to contain AB3 antibodies recognizing the original antigen, CEA, both in enzyme immunoassay and by immunoperoxidase staining of human colon carcinoma. These results open the perspective of vaccination against colorectal carcinoma through the use of anti-idiotype antibodies as antigen substitutes."} {"id": "PMID:1281820", "title": "Methylation of the 5' flanking sequences of the ribosomal DNA in human cell lines and in a human-hamster hybrid cell line.", "content": "In a human lymphoblastoid cell line (Z83) in which rDNA genes on chromosome 22 are amplified but transcribed at a low level, immunocytological studies with antibodies to 5 methylcytidine provided evidence for hypermethylation of the rDNA. The extent of methylation of the 5' flanking sequences of the ribosomal DNA was examined by comparing the size of restriction fragments obtained by digestion of genomic DNA with EcoRI and HpaII or EcoRI and MspI. Southern blots indicated hypermethylation of the 5' flanking sequences of many copies of rRNA genes in these cells, but not in a control lymphoblastoid cell line without rDNA amplification. Results obtained with a somatic hybrid human-hamster cell line, in which the rRNA genes on the single human chromosome 22 are inactive, showed that only a small fraction of the CCGG sites in the 5' flanking sequences of the transcriptionally silent rRNA genes in this hybrid were methylated. Since inactive rRNA genes can show such a minimal level of methylation, it is likely that the extreme hypermethylation of the amplified rRNA genes in Z83 occurred in association with their inactivation rather than following it.", "contents": "Methylation of the 5' flanking sequences of the ribosomal DNA in human cell lines and in a human-hamster hybrid cell line. In a human lymphoblastoid cell line (Z83) in which rDNA genes on chromosome 22 are amplified but transcribed at a low level, immunocytological studies with antibodies to 5 methylcytidine provided evidence for hypermethylation of the rDNA. The extent of methylation of the 5' flanking sequences of the ribosomal DNA was examined by comparing the size of restriction fragments obtained by digestion of genomic DNA with EcoRI and HpaII or EcoRI and MspI. Southern blots indicated hypermethylation of the 5' flanking sequences of many copies of rRNA genes in these cells, but not in a control lymphoblastoid cell line without rDNA amplification. Results obtained with a somatic hybrid human-hamster cell line, in which the rRNA genes on the single human chromosome 22 are inactive, showed that only a small fraction of the CCGG sites in the 5' flanking sequences of the transcriptionally silent rRNA genes in this hybrid were methylated. Since inactive rRNA genes can show such a minimal level of methylation, it is likely that the extreme hypermethylation of the amplified rRNA genes in Z83 occurred in association with their inactivation rather than following it."} {"id": "PMID:1281821", "title": "Preferential accumulation of mature NK cells during human immunosenescence.", "content": "The major histocompatibility complex-unrestricted, cell-mediated, constitutive anti-tumor cytotoxic function of natural killer cells is highly preserved in healthy elderly. A study of the dynamics of expression of natural killer cell-associated phenotypes during immunosenescence shows that selective, bidirectional, and disproportionate changes in certain natural killer cell subset number and ratio take place during aging. The mean natural killer cell subset ratio (%CD16+CD57+ over %CD56+CD57-) gradually increases from a young adult level of 0.7 to 4.6 with advancing age predominantly due to a tripling of %CD16+57+ cells as opposed to a moderate decrease (-54%) in %CD56+57- phenotype. The parallel increase in natural killer phenotype ratio and cytotoxic activity might represent a shift in the maturity status of these cells. Based on these findings, a model of natural killer cell immunosenescence is proposed. It is concluded that not all immunosenescent changes need be detrimental; some may even improve the potential for survival and represent an adaptational immunosenescent change.", "contents": "Preferential accumulation of mature NK cells during human immunosenescence. The major histocompatibility complex-unrestricted, cell-mediated, constitutive anti-tumor cytotoxic function of natural killer cells is highly preserved in healthy elderly. A study of the dynamics of expression of natural killer cell-associated phenotypes during immunosenescence shows that selective, bidirectional, and disproportionate changes in certain natural killer cell subset number and ratio take place during aging. The mean natural killer cell subset ratio (%CD16+CD57+ over %CD56+CD57-) gradually increases from a young adult level of 0.7 to 4.6 with advancing age predominantly due to a tripling of %CD16+57+ cells as opposed to a moderate decrease (-54%) in %CD56+57- phenotype. The parallel increase in natural killer phenotype ratio and cytotoxic activity might represent a shift in the maturity status of these cells. Based on these findings, a model of natural killer cell immunosenescence is proposed. It is concluded that not all immunosenescent changes need be detrimental; some may even improve the potential for survival and represent an adaptational immunosenescent change."} {"id": "PMID:1281822", "title": "Acidic fibroblast growth factor modulates gene expression in the rat thyroid in vivo.", "content": "We have recently demonstrated that the iv administration of acidic fibroblast growth factor (a-FGF) to rats for 6 days results in a marked increase in thyroid weight with colloid accumulation and flat, quiescent follicular cells. Whereas a-FGF administration consistently increases thyroid weight, there are only minor alterations in serum TSH and thyroid hormones, and no change in intrathyroidal metabolism of 125I metabolism. In the present work, we studied the effects of 1 or 6 daily injections of a-FGF (60 micrograms/kg BW) or vehicle on the mRNA levels for histone, c-fos, actin, type I 5' deiodinase (5'D-I), thyroid peroxidase, and thyroglobulin and cathepsin D in the thyroid, liver and bone. Rats were sacrificed 0.5, 2, 4, 8 and 24 h after the 1st or the 6th a-FGF injection and thyroid, liver, and calvarium were removed. The relative amounts of mRNAs were determined by slot blot analysis. There was a 43% increase in thyroid weight in rats treated with a-FGF for 6 days compared to vehicle-treated rats. We observed an increase in c-fos mRNA content in the thyroid gland 0.5 to 4 h after 1 or 6 injections of a-FGF. In contrast, treatment with a-FGF for 1 or 6 days did not affect histone mRNA content, a marker of proliferative activity or actin mRNA levels. Treatment with a-FGF caused a marked decrease in thyroid 5' D-I mRNA content in the thyroid. The decrease was present 2 h after the first injection and reached a nadir 8 h later.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Acidic fibroblast growth factor modulates gene expression in the rat thyroid in vivo. We have recently demonstrated that the iv administration of acidic fibroblast growth factor (a-FGF) to rats for 6 days results in a marked increase in thyroid weight with colloid accumulation and flat, quiescent follicular cells. Whereas a-FGF administration consistently increases thyroid weight, there are only minor alterations in serum TSH and thyroid hormones, and no change in intrathyroidal metabolism of 125I metabolism. In the present work, we studied the effects of 1 or 6 daily injections of a-FGF (60 micrograms/kg BW) or vehicle on the mRNA levels for histone, c-fos, actin, type I 5' deiodinase (5'D-I), thyroid peroxidase, and thyroglobulin and cathepsin D in the thyroid, liver and bone. Rats were sacrificed 0.5, 2, 4, 8 and 24 h after the 1st or the 6th a-FGF injection and thyroid, liver, and calvarium were removed. The relative amounts of mRNAs were determined by slot blot analysis. There was a 43% increase in thyroid weight in rats treated with a-FGF for 6 days compared to vehicle-treated rats. We observed an increase in c-fos mRNA content in the thyroid gland 0.5 to 4 h after 1 or 6 injections of a-FGF. In contrast, treatment with a-FGF for 1 or 6 days did not affect histone mRNA content, a marker of proliferative activity or actin mRNA levels. Treatment with a-FGF caused a marked decrease in thyroid 5' D-I mRNA content in the thyroid. The decrease was present 2 h after the first injection and reached a nadir 8 h later.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281823", "title": "Sialyl ligands facilitate lymphocyte accumulation during inflammation of the central nervous system.", "content": "Combined models of cytokine-induced inflammation in the skin and spinal cord of the rat were utilised to demonstrate in vivo that circulating lymphocytes depend upon sialylated adhesion molecules on their surface for maximal recruitment into inflammatory sites in both tissues. When radiolabelled normal spleen cells were incubated with sialidase from Vibrio cholerae or Clostridium perfringens, or with the specific sialic acid-binding lectin from Limax flavus, prior to being washed and injected intravenously into rats, they accumulated significantly less than untreated control cells into tumor necrosis factor (TNF)-activated spinal cord and skin. Pretreatment of splenocytes with sialidase plus the competitive inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DDN) partially restored the accumulation of radiolabelled cells at both inflammatory sites, providing evidence for the specificity of sialidase treatment and the importance of sialyl residues. Pretreatment of macrophage-depleted spleen lymphocytes, or ovalbumin-specific W3/25+ (CD4) cell line T lymphocytes with sialidase produced similar decrements in accumulation at inflammatory sites, demonstrating that lymphocytes, including memory T cells, were relying on sialyl ligands for maximal recruitment. Results from this in vivo study are interpreted as providing indirect evidence that inducible sialyl-binding molecules, probably of the 'selectin' type, occur to a functionally significant extent on activated central nervous system (CNS) endothelium. We speculate that such carbohydrate-binding adhesion molecules may play an important role in the recruitment of inflammatory cells during the formation of CNS lesions in diseases such as the encephalomyelitides and multiple sclerosis.", "contents": "Sialyl ligands facilitate lymphocyte accumulation during inflammation of the central nervous system. Combined models of cytokine-induced inflammation in the skin and spinal cord of the rat were utilised to demonstrate in vivo that circulating lymphocytes depend upon sialylated adhesion molecules on their surface for maximal recruitment into inflammatory sites in both tissues. When radiolabelled normal spleen cells were incubated with sialidase from Vibrio cholerae or Clostridium perfringens, or with the specific sialic acid-binding lectin from Limax flavus, prior to being washed and injected intravenously into rats, they accumulated significantly less than untreated control cells into tumor necrosis factor (TNF)-activated spinal cord and skin. Pretreatment of splenocytes with sialidase plus the competitive inhibitor 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DDN) partially restored the accumulation of radiolabelled cells at both inflammatory sites, providing evidence for the specificity of sialidase treatment and the importance of sialyl residues. Pretreatment of macrophage-depleted spleen lymphocytes, or ovalbumin-specific W3/25+ (CD4) cell line T lymphocytes with sialidase produced similar decrements in accumulation at inflammatory sites, demonstrating that lymphocytes, including memory T cells, were relying on sialyl ligands for maximal recruitment. Results from this in vivo study are interpreted as providing indirect evidence that inducible sialyl-binding molecules, probably of the 'selectin' type, occur to a functionally significant extent on activated central nervous system (CNS) endothelium. We speculate that such carbohydrate-binding adhesion molecules may play an important role in the recruitment of inflammatory cells during the formation of CNS lesions in diseases such as the encephalomyelitides and multiple sclerosis."} {"id": "PMID:1281824", "title": "Correlation of autoantibody titres with central nervous system pathology in experimental African trypanosomiasis.", "content": "CD-1 mice infected with the protozoan parasite Trypanosoma brucei brucei developed few signs of central nervous system pathology associated with the invasion of the central nervous system by these parasites and did not survive beyond 5-6 weeks with deaths common before this time point. However, use of the trypanocidal drug diminazene aceturate (40 mg/kg), which fails to cross the blood-brain barrier, on day 21 post-infection led to the development of central nervous system pathology similar to that seen in the fatal post-treatment reactive encephalopathies that can occur in human African trypanosomiasis. Enzyme-linked immunosorbent assays were used to measure autoantibody titres to double-stranded DNA, myelin basic protein and to the myelin-specific galactocerebrosides and gangliosides in groups of infected mice, with or without the post-treatment reaction, on day 30 post-infection and compared with uninfected controls. Infection with T. brucei brucei raised the titres of all of these autoantibodies. Treatment of infected mice with diminazene aceturate resulted in elevated levels of all of these autoantibodies compared to the untreated animals. There was a strong positive correlation between the central nervous system pathology and the levels of autoantibodies to myelin basic protein, galactocerebrosides and gangliosides, but not to double-stranded DNA. The elevated titres observed may be a consequence of the polyclonal B cell activation that is believed to occur in African trypanosomiasis, parasite epitopes that are cross-reactive with these central nervous system (CNS)-specific antigens or result from the CNS damage associated with sub-curative chemotherapy.", "contents": "Correlation of autoantibody titres with central nervous system pathology in experimental African trypanosomiasis. CD-1 mice infected with the protozoan parasite Trypanosoma brucei brucei developed few signs of central nervous system pathology associated with the invasion of the central nervous system by these parasites and did not survive beyond 5-6 weeks with deaths common before this time point. However, use of the trypanocidal drug diminazene aceturate (40 mg/kg), which fails to cross the blood-brain barrier, on day 21 post-infection led to the development of central nervous system pathology similar to that seen in the fatal post-treatment reactive encephalopathies that can occur in human African trypanosomiasis. Enzyme-linked immunosorbent assays were used to measure autoantibody titres to double-stranded DNA, myelin basic protein and to the myelin-specific galactocerebrosides and gangliosides in groups of infected mice, with or without the post-treatment reaction, on day 30 post-infection and compared with uninfected controls. Infection with T. brucei brucei raised the titres of all of these autoantibodies. Treatment of infected mice with diminazene aceturate resulted in elevated levels of all of these autoantibodies compared to the untreated animals. There was a strong positive correlation between the central nervous system pathology and the levels of autoantibodies to myelin basic protein, galactocerebrosides and gangliosides, but not to double-stranded DNA. The elevated titres observed may be a consequence of the polyclonal B cell activation that is believed to occur in African trypanosomiasis, parasite epitopes that are cross-reactive with these central nervous system (CNS)-specific antigens or result from the CNS damage associated with sub-curative chemotherapy."} {"id": "PMID:1281825", "title": "Mimicry between HTLV-I and myelin basic protein: no response in HTLV-I-associated myelopathy patients.", "content": "The reactivity to a peptide from the HTLV-I polyprotein (FKLPGLNSR) and a similar sequence from myelin basic protein (MBP) (FKLGGRDSR) was examined in relation to the proposal that mimicry of MBP by HTLV-I could be involved in autoimmune responses in HTLV-I-associated myelopathy (HAM). It was found that rabbit antibodies raised against the HTLV-I peptide recognised both peptides, with a titre of 1/10240 to the HTLV-I peptide and 1/5220 to the MBP peptide. Human sera from HAM patients and a HTLV-I carrier without HAM showed slightly higher responses to the HTLV-I peptide compared to the responses from uninfected human sera. HAM patients had greater responses to the HTLV-I peptide than to the similar MBP peptide and an unrelated bovine MBP peptide. There was no recognition of the peptides by peripheral blood lymphocytes from HAM patients or a HTLV-I carrier without HAM. It was concluded that although cross-reactivity was demonstrated in rabbits and the HTLV-I peptide was recognised by sera from HAM patients, the epitope does not appear to evoke a mimicking response to the similar region in MBP. Hence it is not likely to be involved in the pathogenesis of HAM through molecular mimicry.", "contents": "Mimicry between HTLV-I and myelin basic protein: no response in HTLV-I-associated myelopathy patients. The reactivity to a peptide from the HTLV-I polyprotein (FKLPGLNSR) and a similar sequence from myelin basic protein (MBP) (FKLGGRDSR) was examined in relation to the proposal that mimicry of MBP by HTLV-I could be involved in autoimmune responses in HTLV-I-associated myelopathy (HAM). It was found that rabbit antibodies raised against the HTLV-I peptide recognised both peptides, with a titre of 1/10240 to the HTLV-I peptide and 1/5220 to the MBP peptide. Human sera from HAM patients and a HTLV-I carrier without HAM showed slightly higher responses to the HTLV-I peptide compared to the responses from uninfected human sera. HAM patients had greater responses to the HTLV-I peptide than to the similar MBP peptide and an unrelated bovine MBP peptide. There was no recognition of the peptides by peripheral blood lymphocytes from HAM patients or a HTLV-I carrier without HAM. It was concluded that although cross-reactivity was demonstrated in rabbits and the HTLV-I peptide was recognised by sera from HAM patients, the epitope does not appear to evoke a mimicking response to the similar region in MBP. Hence it is not likely to be involved in the pathogenesis of HAM through molecular mimicry."} {"id": "PMID:1281826", "title": "Suramin rapidly alters cellular tyrosine phosphorylation in prostate cancer cell lines.", "content": "Suramin, a synthetic polysulfonated anionic compound, is known to abrogate the activity of a variety of growth factors that serve as ligands for receptor-class protein-tyrosine kinases. Based on this information, we initially hypothesized that suramin treatment would be associated with decreased tyrosine phosphorylation. Upon testing this hypothesis in prostate cancer cell lines, we found that the most conspicuous effect of suramin was to increase the tyrosine phosphorylation of several distinct proteins. Further analyses indicate that suramin-induced increases in tyrosine phosphorylation represent a generalized, but not universal, phenomenon found in cell lines derived from a variety of human tissues. These rapid and specific suramin-induced alterations represent a novel finding for a non-polypeptide pharmaceutical agent and question the hypothesis that suramin exerts its antitumor action simply by abrogation of growth factor action.", "contents": "Suramin rapidly alters cellular tyrosine phosphorylation in prostate cancer cell lines. Suramin, a synthetic polysulfonated anionic compound, is known to abrogate the activity of a variety of growth factors that serve as ligands for receptor-class protein-tyrosine kinases. Based on this information, we initially hypothesized that suramin treatment would be associated with decreased tyrosine phosphorylation. Upon testing this hypothesis in prostate cancer cell lines, we found that the most conspicuous effect of suramin was to increase the tyrosine phosphorylation of several distinct proteins. Further analyses indicate that suramin-induced increases in tyrosine phosphorylation represent a generalized, but not universal, phenomenon found in cell lines derived from a variety of human tissues. These rapid and specific suramin-induced alterations represent a novel finding for a non-polypeptide pharmaceutical agent and question the hypothesis that suramin exerts its antitumor action simply by abrogation of growth factor action."} {"id": "PMID:1281827", "title": "Lipopolysaccharide binding protein enhances the responsiveness of alveolar macrophages to bacterial lipopolysaccharide. Implications for cytokine production in normal and injured lungs.", "content": "A plasma lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of rabbit peritoneal macrophages and human blood monocytes to endotoxin (LPS). We investigated whether LBP is present in lung fluids and the effects of LBP on the response of lung macrophages to LPS. Immunoreactive LBP was detectable in the lavage fluids of patients with the adult respiratory distress syndrome by immunoprecipitation followed by Western blotting, and also by specific immunoassay. In rabbits, the LBP appeared to originate outside of the lungs, inasmuch as mRNA transcripts for LBP were identified in total cellular RNA from liver, but not from lung homogenates or alveolar macrophages. Purified LBP enhanced the response of human and rabbit alveolar macrophages to both smooth form LPS (Escherichia coli O111B:4) and rough form LPS (Salmonella minnesota Re595). In the presence of LBP and LPS, the onset of tumor necrosis factor-alpha (TNF alpha) production occurred earlier and at an LPS threshold dose that was as much as 1,000-fold lower for both types of LPS. In rabbit alveolar macrophages treated with LBP and LPS, TNF alpha mRNA appeared earlier, reached higher levels, and had a prolonged half-life as compared with LPS treatment alone. Neither LPS nor LPS and LBP affected pHi or [Cai++] in alveolar macrophages. Specific monoclonal antibodies to CD14, a receptor that binds LPS/LBP complexes, inhibited TNF alpha production by human alveolar macrophages stimulated with LPS alone or with LPS/LBP complexes, indicating the importance of CD14 in mediating the effects of LPS on alveolar macrophages. Thus, immunoreactive LBP accumulates in lung lavage fluids in patients with lung injury and enhances LPS-stimulated TNF alpha gene expression in alveolar macrophages by a pathway that depends on the CD14 receptor. LBP may play an important role in augmenting TNF alpha expression by alveolar macrophages within the lungs.", "contents": "Lipopolysaccharide binding protein enhances the responsiveness of alveolar macrophages to bacterial lipopolysaccharide. Implications for cytokine production in normal and injured lungs. A plasma lipopolysaccharide (LPS)-binding protein (LBP) has been shown to regulate the response of rabbit peritoneal macrophages and human blood monocytes to endotoxin (LPS). We investigated whether LBP is present in lung fluids and the effects of LBP on the response of lung macrophages to LPS. Immunoreactive LBP was detectable in the lavage fluids of patients with the adult respiratory distress syndrome by immunoprecipitation followed by Western blotting, and also by specific immunoassay. In rabbits, the LBP appeared to originate outside of the lungs, inasmuch as mRNA transcripts for LBP were identified in total cellular RNA from liver, but not from lung homogenates or alveolar macrophages. Purified LBP enhanced the response of human and rabbit alveolar macrophages to both smooth form LPS (Escherichia coli O111B:4) and rough form LPS (Salmonella minnesota Re595). In the presence of LBP and LPS, the onset of tumor necrosis factor-alpha (TNF alpha) production occurred earlier and at an LPS threshold dose that was as much as 1,000-fold lower for both types of LPS. In rabbit alveolar macrophages treated with LBP and LPS, TNF alpha mRNA appeared earlier, reached higher levels, and had a prolonged half-life as compared with LPS treatment alone. Neither LPS nor LPS and LBP affected pHi or [Cai++] in alveolar macrophages. Specific monoclonal antibodies to CD14, a receptor that binds LPS/LBP complexes, inhibited TNF alpha production by human alveolar macrophages stimulated with LPS alone or with LPS/LBP complexes, indicating the importance of CD14 in mediating the effects of LPS on alveolar macrophages. Thus, immunoreactive LBP accumulates in lung lavage fluids in patients with lung injury and enhances LPS-stimulated TNF alpha gene expression in alveolar macrophages by a pathway that depends on the CD14 receptor. LBP may play an important role in augmenting TNF alpha expression by alveolar macrophages within the lungs."} {"id": "PMID:1281828", "title": "Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease.", "content": "Changes in the structure of the proteoglycan aggrecan (PG) of articular cartilage were determined immunochemically by RIA and gel chromatography and related to cartilage degeneration documented histologically by the Mankin grading system. Monoclonal antibodies to glycosaminoglycan epitopes were used. In all cartilages, three chondroitin sulfate (CS)-rich populations of large size were observed in addition to a smaller keratan sulfate (KS)-rich population. In grades 7-13 OA cartilages (phase II), molecules were significantly larger than the equivalent molecules of grades 2-6 (phase I). CS chain lengths remained unchanged. In most OA cartilages, a CS epitope 846 was elevated in content, this being most marked in phase II (mean: fivefold). Loss of uronic acid, KS, and hyaluronic acid were only pronounced in phase II OA because of variations in normal contents. Aggregation of PG was unchanged (50-60%) or reduced in OA cartilages, but molecules bearing epitope 846 exhibited almost complete aggregation in normal cartilages. This study provides evidence for the capacity of OA cartilage to synthesize new aggrecan molecules to replace those damaged and lost by disease-related changes. It also defines two phases of PG change in OA: an early predominantly degenerate phase I followed by a net reparative phase II accompanied by net loss of these molecules.", "contents": "Studies of the articular cartilage proteoglycan aggrecan in health and osteoarthritis. Evidence for molecular heterogeneity and extensive molecular changes in disease. Changes in the structure of the proteoglycan aggrecan (PG) of articular cartilage were determined immunochemically by RIA and gel chromatography and related to cartilage degeneration documented histologically by the Mankin grading system. Monoclonal antibodies to glycosaminoglycan epitopes were used. In all cartilages, three chondroitin sulfate (CS)-rich populations of large size were observed in addition to a smaller keratan sulfate (KS)-rich population. In grades 7-13 OA cartilages (phase II), molecules were significantly larger than the equivalent molecules of grades 2-6 (phase I). CS chain lengths remained unchanged. In most OA cartilages, a CS epitope 846 was elevated in content, this being most marked in phase II (mean: fivefold). Loss of uronic acid, KS, and hyaluronic acid were only pronounced in phase II OA because of variations in normal contents. Aggregation of PG was unchanged (50-60%) or reduced in OA cartilages, but molecules bearing epitope 846 exhibited almost complete aggregation in normal cartilages. This study provides evidence for the capacity of OA cartilage to synthesize new aggrecan molecules to replace those damaged and lost by disease-related changes. It also defines two phases of PG change in OA: an early predominantly degenerate phase I followed by a net reparative phase II accompanied by net loss of these molecules."} {"id": "PMID:1281829", "title": "Function of pulmonary M2 muscarinic receptors in antigen-challenged guinea pigs is restored by heparin and poly-L-glutamate.", "content": "The effect of heparin and poly-L-glutamate on the function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lung was tested in antigen-challenged guinea pigs. After antigen challenge, M2 receptor function is decreased, thus increasing release of acetylcholine from the vagus and potentiating vagally induced bronchoconstriction. Guinea pigs were anesthetized, tracheostomized, vagotomized, paralyzed, and ventilated. Electrical stimulation of the vagi caused bronchoconstriction and bradycardia. In controls, pilocarpine attenuated vagally induced bronchoconstriction by stimulating neuronal M2 muscarinic receptors. Conversely, blocking these autoreceptors with gallamine potentiated vagally induced bronchoconstriction. In challenged animals the effects of both drugs were markedly reduced, confirming M2 receptor dysfunction. 20 min after heparin or poly-L-glutamate, the effects of both pilocarpine and gallamine on vagally induced bronchoconstriction were restored, demonstrating recovery of M2 receptor function. Neither heparin nor poly-L-glutamate affected vagally induced responses in control animals. Thus antigen-induced dysfunction of M2 receptors can be reversed by polyanionic polysaccharides (heparin) or polyanionic peptides (poly-L-glutamate). This suggests that a polycationic substance such as eosinophil major basic protein, cationic protein, or peroxidase may be responsible for antigen-induced pulmonary M2 receptor dysfunction.", "contents": "Function of pulmonary M2 muscarinic receptors in antigen-challenged guinea pigs is restored by heparin and poly-L-glutamate. The effect of heparin and poly-L-glutamate on the function of inhibitory M2 muscarinic autoreceptors on parasympathetic nerves in the lung was tested in antigen-challenged guinea pigs. After antigen challenge, M2 receptor function is decreased, thus increasing release of acetylcholine from the vagus and potentiating vagally induced bronchoconstriction. Guinea pigs were anesthetized, tracheostomized, vagotomized, paralyzed, and ventilated. Electrical stimulation of the vagi caused bronchoconstriction and bradycardia. In controls, pilocarpine attenuated vagally induced bronchoconstriction by stimulating neuronal M2 muscarinic receptors. Conversely, blocking these autoreceptors with gallamine potentiated vagally induced bronchoconstriction. In challenged animals the effects of both drugs were markedly reduced, confirming M2 receptor dysfunction. 20 min after heparin or poly-L-glutamate, the effects of both pilocarpine and gallamine on vagally induced bronchoconstriction were restored, demonstrating recovery of M2 receptor function. Neither heparin nor poly-L-glutamate affected vagally induced responses in control animals. Thus antigen-induced dysfunction of M2 receptors can be reversed by polyanionic polysaccharides (heparin) or polyanionic peptides (poly-L-glutamate). This suggests that a polycationic substance such as eosinophil major basic protein, cationic protein, or peroxidase may be responsible for antigen-induced pulmonary M2 receptor dysfunction."} {"id": "PMID:1281830", "title": "Hypoxia-mediated induction of endothelial cell interleukin-1 alpha. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface.", "content": "Tissue injury that accompanies hypoxemia/reoxygenation shares features with the host response in inflammation, suggesting that cytokines, such as IL-1, may act as mediators in this setting. Human endothelial cells (ECs) subjected to hypoxia (PO2 approximately 12-14 Torr) elaborated IL-1 activity into conditioned media in a time-dependent manner; this activity was completely neutralized by an antibody to IL-1 alpha. Production of IL-1 activity by hypoxic ECs was associated with an increase in the level of mRNA for IL-1 alpha, and was followed by induction of endothelial-leukocyte adhesion molecule-1 and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) during reoxygenation. During reoxygenation there was a three- to five-fold increased adherence of leukocytes, partly blocked by antibodies to endothelial-leukocyte adhesion molecule-1 and ICAM-1. Suppressing endothelial-derived IL-1, using either antibodies to IL-1 alpha, specific antisense oligonucleotides or the IL-1 receptor antagonist, decreased leukocyte adherence to reoxygenated ECs, emphasizing the integral role of IL-1 in the adherence phenomenon. Mice subjected to hypoxia (PO2 approximately 30-40 Torr) displayed increased plasma levels of IL-1 alpha, induction of IL-1 alpha mRNA in the lung, and enhanced expression of ICAM-1 in pulmonary tissue compared with normoxic controls. These data suggest that hypoxia is a stimulus which induces EC synthesis and release of IL-1 alpha, resulting in an autocrine enhancement in the expression of adhesion molecules.", "contents": "Hypoxia-mediated induction of endothelial cell interleukin-1 alpha. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface. Tissue injury that accompanies hypoxemia/reoxygenation shares features with the host response in inflammation, suggesting that cytokines, such as IL-1, may act as mediators in this setting. Human endothelial cells (ECs) subjected to hypoxia (PO2 approximately 12-14 Torr) elaborated IL-1 activity into conditioned media in a time-dependent manner; this activity was completely neutralized by an antibody to IL-1 alpha. Production of IL-1 activity by hypoxic ECs was associated with an increase in the level of mRNA for IL-1 alpha, and was followed by induction of endothelial-leukocyte adhesion molecule-1 and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) during reoxygenation. During reoxygenation there was a three- to five-fold increased adherence of leukocytes, partly blocked by antibodies to endothelial-leukocyte adhesion molecule-1 and ICAM-1. Suppressing endothelial-derived IL-1, using either antibodies to IL-1 alpha, specific antisense oligonucleotides or the IL-1 receptor antagonist, decreased leukocyte adherence to reoxygenated ECs, emphasizing the integral role of IL-1 in the adherence phenomenon. Mice subjected to hypoxia (PO2 approximately 30-40 Torr) displayed increased plasma levels of IL-1 alpha, induction of IL-1 alpha mRNA in the lung, and enhanced expression of ICAM-1 in pulmonary tissue compared with normoxic controls. These data suggest that hypoxia is a stimulus which induces EC synthesis and release of IL-1 alpha, resulting in an autocrine enhancement in the expression of adhesion molecules."} {"id": "PMID:1281831", "title": "Characterization of an acquired inhibitor to coagulation factor V. Antibody binding to the second C-type domain of factor V inhibits the binding of factor V to phosphatidylserine and neutralizes procoagulant activity.", "content": "Coagulation Factor V is an essential component of the prothrombinase complex, which activates the zymogen prothrombin to thrombin. A patient was described who developed a Factor V inhibitor that neutralized the procoagulant activity of Factor V and resulted in a fatal hemorrhagic diathesis (Coots, M. C., A. F. Muhleman, and H. I. Glueck. 1978. Am. J. Hematol. 4:193-206). This inhibitor was shown to be an IgG antibody that bound to the light chain of Factor V. Using a series of light chain deletion mutants, we have found that this antibody binds to the second C-type domain of the light chain. Both inhibitor IgG and Fab fragments rapidly neutralized the procoagulant activity of Factor Va, implying that the neutralization resulted from specific binding to the C2 domain. We have previously demonstrated that deletion of the C2 domain results in loss of procoagulant activity, as well as loss of phosphatidylserine-specific binding. Confirming these results, both inhibitor IgG and Fab fragments interfered with phosphatidylserine-specific binding of Factor V. Conversely, preincubation of Factor Va with procoagulant phospholipids protected the cofactor from inactivation by the inhibitor. Our results suggest that this inhibitor neutralizes the procoagulant activity of Factor Va by interfering with the C2-mediated interaction with phospholipid surfaces, thereby disrupting formation of the prothrombinase complex.", "contents": "Characterization of an acquired inhibitor to coagulation factor V. Antibody binding to the second C-type domain of factor V inhibits the binding of factor V to phosphatidylserine and neutralizes procoagulant activity. Coagulation Factor V is an essential component of the prothrombinase complex, which activates the zymogen prothrombin to thrombin. A patient was described who developed a Factor V inhibitor that neutralized the procoagulant activity of Factor V and resulted in a fatal hemorrhagic diathesis (Coots, M. C., A. F. Muhleman, and H. I. Glueck. 1978. Am. J. Hematol. 4:193-206). This inhibitor was shown to be an IgG antibody that bound to the light chain of Factor V. Using a series of light chain deletion mutants, we have found that this antibody binds to the second C-type domain of the light chain. Both inhibitor IgG and Fab fragments rapidly neutralized the procoagulant activity of Factor Va, implying that the neutralization resulted from specific binding to the C2 domain. We have previously demonstrated that deletion of the C2 domain results in loss of procoagulant activity, as well as loss of phosphatidylserine-specific binding. Confirming these results, both inhibitor IgG and Fab fragments interfered with phosphatidylserine-specific binding of Factor V. Conversely, preincubation of Factor Va with procoagulant phospholipids protected the cofactor from inactivation by the inhibitor. Our results suggest that this inhibitor neutralizes the procoagulant activity of Factor Va by interfering with the C2-mediated interaction with phospholipid surfaces, thereby disrupting formation of the prothrombinase complex."} {"id": "PMID:1281832", "title": "Altered epitope expression of human interstitial fluid apolipoprotein A-I reduces its ability to activate lecithin cholesterol acyl transferase.", "content": "In human peripheral interstitial fluid, esterification of cholesterol by lecithin cholesterol acyltransferase (LCAT) was found to occur at a rate of only 10% of that in plasma (5.6 +/- 1.8 compared with 55.6 +/- 7.8 nmol/ml per h). Measurement of cholesterol esterification in the presence of excess reconstituted apoA-I HDL (rA-I HDL) revealed an LCAT activity in interstitial fluid of 24% of that in plasma, indicating that the low rate of esterification could not be caused by limiting mass of LCAT enzyme. When plasma was diluted to the same concentration as in interstitial fluid, the percent cholesterol esterification rate was the same as undiluted plasma and significantly higher than that of interstitial fluid. These findings led us to postulate that poor activation of LCAT in interstitial fluid may result from a change in conformation in apoA-I. To test this hypothesis, a monoclonal antibody AI-11 that inhibits apoA-I activation of LCAT was used to measure apoA-I in interstitial fluid and plasma. Antibody AI-11 recognized interstitial fluid apoA-I poorly, whereas a polyclonal antibody recognized interstitial fluid apoA-I normally. Incubation of antibody AI-11 with high density lipoprotein or rA-I HDL inhibited apoA-I activation of LCAT. We conclude that the altered conformation of apoA-I in interstitial fluid may render it a poor activator of LCAT.", "contents": "Altered epitope expression of human interstitial fluid apolipoprotein A-I reduces its ability to activate lecithin cholesterol acyl transferase. In human peripheral interstitial fluid, esterification of cholesterol by lecithin cholesterol acyltransferase (LCAT) was found to occur at a rate of only 10% of that in plasma (5.6 +/- 1.8 compared with 55.6 +/- 7.8 nmol/ml per h). Measurement of cholesterol esterification in the presence of excess reconstituted apoA-I HDL (rA-I HDL) revealed an LCAT activity in interstitial fluid of 24% of that in plasma, indicating that the low rate of esterification could not be caused by limiting mass of LCAT enzyme. When plasma was diluted to the same concentration as in interstitial fluid, the percent cholesterol esterification rate was the same as undiluted plasma and significantly higher than that of interstitial fluid. These findings led us to postulate that poor activation of LCAT in interstitial fluid may result from a change in conformation in apoA-I. To test this hypothesis, a monoclonal antibody AI-11 that inhibits apoA-I activation of LCAT was used to measure apoA-I in interstitial fluid and plasma. Antibody AI-11 recognized interstitial fluid apoA-I poorly, whereas a polyclonal antibody recognized interstitial fluid apoA-I normally. Incubation of antibody AI-11 with high density lipoprotein or rA-I HDL inhibited apoA-I activation of LCAT. We conclude that the altered conformation of apoA-I in interstitial fluid may render it a poor activator of LCAT."} {"id": "PMID:1281833", "title": "Plasticity of neuroblastoma tumor cells to differentiate along a fetal adrenal ganglionic lineage predicts for improved patient survival.", "content": "We have recently presented a model of human adrenal medullary histogenesis that incorporates all neural crest-derived lineages (chromaffin, sustentacular, and ganglionic) known to compose this tissue. To determine if neuroblastomas correspond to the arrested maturation of embryonal adrenal medullary cells, we evaluated the expression of adrenal medullary developmental markers in 81 neuroblastoma tumors. We found that patterns of chromaffin-related gene expression in these tumors correlated exactly with the patterns observed during maturation of adrenal medullary cells (P2 < 10(-5). In a multivariate Cox proportional hazards analysis of developmental marker expression and other well-recognized prognostic variables, evidence of maturation along a fetal ganglionic lineage, as monitored by HNK-1 immunoreactivity (relative risk of 6.42, P2 = 0.0001), and age at diagnosis (relative risk of 5.05, P2 = 0.0042) were independent and significant prognostic indicators of patient survival. These studies demonstrate that neuroblastomas correspond to embryonal adrenal medullary cells arrested at recognizable stages during development, and that evidence of maturation along a fetal ganglionic lineage appears to have major importance in predicting patient survival.", "contents": "Plasticity of neuroblastoma tumor cells to differentiate along a fetal adrenal ganglionic lineage predicts for improved patient survival. We have recently presented a model of human adrenal medullary histogenesis that incorporates all neural crest-derived lineages (chromaffin, sustentacular, and ganglionic) known to compose this tissue. To determine if neuroblastomas correspond to the arrested maturation of embryonal adrenal medullary cells, we evaluated the expression of adrenal medullary developmental markers in 81 neuroblastoma tumors. We found that patterns of chromaffin-related gene expression in these tumors correlated exactly with the patterns observed during maturation of adrenal medullary cells (P2 < 10(-5). In a multivariate Cox proportional hazards analysis of developmental marker expression and other well-recognized prognostic variables, evidence of maturation along a fetal ganglionic lineage, as monitored by HNK-1 immunoreactivity (relative risk of 6.42, P2 = 0.0001), and age at diagnosis (relative risk of 5.05, P2 = 0.0042) were independent and significant prognostic indicators of patient survival. These studies demonstrate that neuroblastomas correspond to embryonal adrenal medullary cells arrested at recognizable stages during development, and that evidence of maturation along a fetal ganglionic lineage appears to have major importance in predicting patient survival."} {"id": "PMID:1281834", "title": "Transforming growth factor alpha protection against drug-induced injury to the rat gastric mucosa in vivo.", "content": "This study was designed to determine whether transforming growth factor alpha (TGF alpha) protects rat gastric mucosa against ethanol- and aspirin-induced injury. Systemic administration of TGF alpha dose-dependently decreased 100% ethanol-induced gastric mucosal injury; a dose of 50 micrograms/kg delivered intraperitoneally 15 min before ethanol decreased macroscopic mucosal injury by > 90%. At the microscopic level, TGF alpha prevented deep gastric necrotic lesions and reduced disruption of surface epithelium. Pretreatment with orogastric TGF alpha (200 micrograms/kg) only partially (40%) decreased macroscopic ethanol damage. Intraperitoneal administration of TGF alpha at a dose of 10 micrograms/kg, which does not significantly inhibit gastric acid secretion, decreased aspirin-induced macroscopic damage by > 80%. TGF alpha protection does not seem to be mediated by prostaglandin, glutathione, or ornithine decarboxylase-related events, as evidenced by lack of influence of the inhibition of their production. Pretreatment with the sulfhydryl blocking agent N-ethylmaleimide partially abolished (40%) the protective effect of TGF alpha. In addition, systemic administration of TGF alpha resulted in a two-fold increase in tyrosine phosphorylation of phospholipase C-gamma 1 and in a time- and dose-dependent increase in levels of immunoreactive insoluble gastric mucin; these events occurred in a time frame consistent with their participation in the protective effect of TGF alpha.", "contents": "Transforming growth factor alpha protection against drug-induced injury to the rat gastric mucosa in vivo. This study was designed to determine whether transforming growth factor alpha (TGF alpha) protects rat gastric mucosa against ethanol- and aspirin-induced injury. Systemic administration of TGF alpha dose-dependently decreased 100% ethanol-induced gastric mucosal injury; a dose of 50 micrograms/kg delivered intraperitoneally 15 min before ethanol decreased macroscopic mucosal injury by > 90%. At the microscopic level, TGF alpha prevented deep gastric necrotic lesions and reduced disruption of surface epithelium. Pretreatment with orogastric TGF alpha (200 micrograms/kg) only partially (40%) decreased macroscopic ethanol damage. Intraperitoneal administration of TGF alpha at a dose of 10 micrograms/kg, which does not significantly inhibit gastric acid secretion, decreased aspirin-induced macroscopic damage by > 80%. TGF alpha protection does not seem to be mediated by prostaglandin, glutathione, or ornithine decarboxylase-related events, as evidenced by lack of influence of the inhibition of their production. Pretreatment with the sulfhydryl blocking agent N-ethylmaleimide partially abolished (40%) the protective effect of TGF alpha. In addition, systemic administration of TGF alpha resulted in a two-fold increase in tyrosine phosphorylation of phospholipase C-gamma 1 and in a time- and dose-dependent increase in levels of immunoreactive insoluble gastric mucin; these events occurred in a time frame consistent with their participation in the protective effect of TGF alpha."} {"id": "PMID:1281835", "title": "T cells in the lesion of experimental autoimmune encephalomyelitis. Enrichment for reactivities to myelin basic protein and to heat shock proteins.", "content": "To characterize the cellular immune response in an autoimmune lesion, we investigated the accumulation of specific T cells in the central nervous system in actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats, using a limiting dilution analysis (LDA) assay for T cells that proliferate in response to antigens. Lymphocytes isolated from the spinal cord infiltrate were compared with cells from the popliteal lymph nodes with respect to frequency of cells responding to basic protein (BP), mycobacterium tuberculosis (MT), the 65-kD heat shock protein (hsp65), allogeneic brown norway spleen cells, and concanavalin A. Additionally, we compared the BP frequency in acute EAE of cells from the spinal cord, peripheral blood, spleen and lymph nodes, and the spinal cord and lymph node after recovery from EAE. We found that acute EAE was associated with marked enrichment of BP-reactive T cells in the spinal cord relative to their frequency in the lymphoid organs and peripheral blood. The infiltrate was also enriched for T cells responding to hsp65; alloreactive T cells, in contrast, were not enriched. The frequency of BP reactive T cells in the spinal cord was highest at the peak of paralysis; however, BP-reactive T cells could still be detected at moderate frequencies after clinical recovery. We established BP- and Mycobacteria-reactive T cell lines from the spinal infiltrates that were CD4+ and TcR alpha beta +. Most of the BP lines were found to react to the major encephalitogenic epitope of guinea pig BP for rats (amino acids 71-90); these lines were found to mediate EAE in naive recipients. T cell lines recognizing other epitopes of BP were not encephalitogenic. All of the lines responsive to Mycobacteria recognized hsp65 or hsp70. These results indicating that the immune infiltrate in active EAE is enriched with cells responding to the autoantigen and to hsp65 were confirmed in EAE adoptively transferred by anti-BP T cell clone.", "contents": "T cells in the lesion of experimental autoimmune encephalomyelitis. Enrichment for reactivities to myelin basic protein and to heat shock proteins. To characterize the cellular immune response in an autoimmune lesion, we investigated the accumulation of specific T cells in the central nervous system in actively induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats, using a limiting dilution analysis (LDA) assay for T cells that proliferate in response to antigens. Lymphocytes isolated from the spinal cord infiltrate were compared with cells from the popliteal lymph nodes with respect to frequency of cells responding to basic protein (BP), mycobacterium tuberculosis (MT), the 65-kD heat shock protein (hsp65), allogeneic brown norway spleen cells, and concanavalin A. Additionally, we compared the BP frequency in acute EAE of cells from the spinal cord, peripheral blood, spleen and lymph nodes, and the spinal cord and lymph node after recovery from EAE. We found that acute EAE was associated with marked enrichment of BP-reactive T cells in the spinal cord relative to their frequency in the lymphoid organs and peripheral blood. The infiltrate was also enriched for T cells responding to hsp65; alloreactive T cells, in contrast, were not enriched. The frequency of BP reactive T cells in the spinal cord was highest at the peak of paralysis; however, BP-reactive T cells could still be detected at moderate frequencies after clinical recovery. We established BP- and Mycobacteria-reactive T cell lines from the spinal infiltrates that were CD4+ and TcR alpha beta +. Most of the BP lines were found to react to the major encephalitogenic epitope of guinea pig BP for rats (amino acids 71-90); these lines were found to mediate EAE in naive recipients. T cell lines recognizing other epitopes of BP were not encephalitogenic. All of the lines responsive to Mycobacteria recognized hsp65 or hsp70. These results indicating that the immune infiltrate in active EAE is enriched with cells responding to the autoantigen and to hsp65 were confirmed in EAE adoptively transferred by anti-BP T cell clone."} {"id": "PMID:1281836", "title": "Fibrinogen degradation product fragment D induces endothelial cell detachment by activation of cell-mediated fibrinolysis.", "content": "We studied the effects of fibrinogen degradation product (FDP) fragment D on endothelial monolayer integrity and the mechanisms of fragment D-induced endothelial cell detachment from the substratum. Incubation of bovine pulmonary artery endothelial cells (BPAEC) with fragment D caused concentration- and time-dependent cell detachment from the substratum. The optimal response occurred at fragment D concentrations of 2 microM and required an incubation time of 24 h. BPAEC challenged with fragment D increased the concentration and activity of urokinase-type plasminogen activator (uPA) in the conditioned medium within 2 to 4 h of incubation. Fragment D also induced the release of tissue-type plasminogen activator, but to a lesser extent than uPA. Fragment D concurrently increased plasminogen activator (PA) activity in a concentration-dependent manner. Increased PA activity was followed by augmentation of cell-associated plasmin activity and subsequent increase in the degradation of 125I-fibrinogen and 125I-vitronectin precoated in the subendothelial matrix. Pretreatment of BPAEC with anti-uPA antibody, and inhibitors of uPA (dansyl-GGACK) and plasmin (aprotinin) prevented approximately 60% of the fragment D-induced endothelial cell detachment. We conclude that FDP fragment D increases secretion of endothelial PAs and enhances the generation of plasmin, thereby contributing to proteolysis of extracellular matrix and endothelial cell detachment. Fragment D may be a critical mediator linking activation of fibrinolysis to vascular endothelial injury in inflammatory disorders.", "contents": "Fibrinogen degradation product fragment D induces endothelial cell detachment by activation of cell-mediated fibrinolysis. We studied the effects of fibrinogen degradation product (FDP) fragment D on endothelial monolayer integrity and the mechanisms of fragment D-induced endothelial cell detachment from the substratum. Incubation of bovine pulmonary artery endothelial cells (BPAEC) with fragment D caused concentration- and time-dependent cell detachment from the substratum. The optimal response occurred at fragment D concentrations of 2 microM and required an incubation time of 24 h. BPAEC challenged with fragment D increased the concentration and activity of urokinase-type plasminogen activator (uPA) in the conditioned medium within 2 to 4 h of incubation. Fragment D also induced the release of tissue-type plasminogen activator, but to a lesser extent than uPA. Fragment D concurrently increased plasminogen activator (PA) activity in a concentration-dependent manner. Increased PA activity was followed by augmentation of cell-associated plasmin activity and subsequent increase in the degradation of 125I-fibrinogen and 125I-vitronectin precoated in the subendothelial matrix. Pretreatment of BPAEC with anti-uPA antibody, and inhibitors of uPA (dansyl-GGACK) and plasmin (aprotinin) prevented approximately 60% of the fragment D-induced endothelial cell detachment. We conclude that FDP fragment D increases secretion of endothelial PAs and enhances the generation of plasmin, thereby contributing to proteolysis of extracellular matrix and endothelial cell detachment. Fragment D may be a critical mediator linking activation of fibrinolysis to vascular endothelial injury in inflammatory disorders."} {"id": "PMID:1281837", "title": "Neutrophil adherence induced by lipopolysaccharide in vitro. Role of plasma component interaction with lipopolysaccharide.", "content": "Endotoxemia results in neutrophil localization within a number of microcirculatory beds, reflecting in part an adhesive interaction between neutrophils and the vascular endothelial cell. In previous studies, endotoxin or lipopolysaccharide (LPS) treatment of rabbits resulted in neutrophil sequestration at LPS concentrations well below those effective at increasing neutrophil adherence in vitro. We hypothesized that LPS-induced neutrophil adherence involved a plasma component. In the absence of plasma, high concentrations of LPS (10 micrograms/ml) were required to increase human neutrophil adherence to endothelial cells in vitro. With the inclusion of as little as 1% plasma or serum, however, the LPS dose-response curve was markedly shifted, resulting in increments in adherence at 10 ng/ml, and the time course of enhanced adherence was accelerated. Pretreatment studies suggested that the effect of LPS was on the neutrophil rather than the endothelial cell. Immunoprecipitation of 0111:B4 LPS paralleled the loss of functional activity, suggesting that LPS was an integral part of the active complex, rather than altering a plasma component to make it active. The incubation of plasma with LPS decreased the apparent molecular mass of LPS from 500-1,000 kD to approximately 100 kD. The disaggregated 0111:B4 LPS eluted in the range of albumin and was able to increase adherence in the absence of additional plasma. Plasma depleted of lipoproteins or heat treated retained activity, suggesting that the interaction of LPS with HDL or complement did not account for the observed findings. An LPS-binding protein isolated from rabbit serum enhanced the adherence-inducing effects of both 0111:B4 and Re595 LPS. Furthermore, the activity of rabbit serum was abolished after incubation with an antibody directed against this LPS-binding protein (LBP). An antibody directed against CD14, the putative receptor of the LPS-LBP complex, prevented the adhesive response to LPS. These data suggest that LPS is disaggregated by an LBP in serum and plasma to form an active LPS-plasma component complex. This putative complex then interacts with CD14 on the neutrophil so as to induce an adhesive state.", "contents": "Neutrophil adherence induced by lipopolysaccharide in vitro. Role of plasma component interaction with lipopolysaccharide. Endotoxemia results in neutrophil localization within a number of microcirculatory beds, reflecting in part an adhesive interaction between neutrophils and the vascular endothelial cell. In previous studies, endotoxin or lipopolysaccharide (LPS) treatment of rabbits resulted in neutrophil sequestration at LPS concentrations well below those effective at increasing neutrophil adherence in vitro. We hypothesized that LPS-induced neutrophil adherence involved a plasma component. In the absence of plasma, high concentrations of LPS (10 micrograms/ml) were required to increase human neutrophil adherence to endothelial cells in vitro. With the inclusion of as little as 1% plasma or serum, however, the LPS dose-response curve was markedly shifted, resulting in increments in adherence at 10 ng/ml, and the time course of enhanced adherence was accelerated. Pretreatment studies suggested that the effect of LPS was on the neutrophil rather than the endothelial cell. Immunoprecipitation of 0111:B4 LPS paralleled the loss of functional activity, suggesting that LPS was an integral part of the active complex, rather than altering a plasma component to make it active. The incubation of plasma with LPS decreased the apparent molecular mass of LPS from 500-1,000 kD to approximately 100 kD. The disaggregated 0111:B4 LPS eluted in the range of albumin and was able to increase adherence in the absence of additional plasma. Plasma depleted of lipoproteins or heat treated retained activity, suggesting that the interaction of LPS with HDL or complement did not account for the observed findings. An LPS-binding protein isolated from rabbit serum enhanced the adherence-inducing effects of both 0111:B4 and Re595 LPS. Furthermore, the activity of rabbit serum was abolished after incubation with an antibody directed against this LPS-binding protein (LBP). An antibody directed against CD14, the putative receptor of the LPS-LBP complex, prevented the adhesive response to LPS. These data suggest that LPS is disaggregated by an LBP in serum and plasma to form an active LPS-plasma component complex. This putative complex then interacts with CD14 on the neutrophil so as to induce an adhesive state."} {"id": "PMID:1281838", "title": "Binding of type 3 reovirus by a domain of the sigma 1 protein important for hemagglutination leads to infection of murine erythroleukemia cells.", "content": "The recognition of cellular receptors by the mammalian reoviruses is an important determinant of cell and tissue tropism exhibited by reovirus strains of different serotypes. To extend our knowledge of the role of reovirus-receptor interactions in reovirus tropism, we determined whether type 1 and type 3 reovirus strains can infect cells derived from erythrocyte precursors. We found that reovirus type 3 Dearing (T3D), but not type 1 Lang, can grow in murine erythroleukemia (MEL) cells. This difference in growth was investigated by using reassortant viruses and we found that the capacity of T3D to infect MEL cells is determined by the viral cell-attachment protein, sigma 1. In experiments using murine monoclonal antibodies (mAbs) that bind to different sigma 1 regions, we show that T3D binding to MEL cells is inhibited by a mAb that identifies a domain important for hemagglutination (HA). We also determined that type 3 strains that can infect murine L cells but do not produce HA do not infect MEL cells. These results suggest that type 3 reovirus binds to and infects erythrocyte precursor cells via a sigma 1 domain important for HA. Moreover, this study suggests that different domains of some viral cell-attachment proteins are used to initiate productive infections of different types of cells.", "contents": "Binding of type 3 reovirus by a domain of the sigma 1 protein important for hemagglutination leads to infection of murine erythroleukemia cells. The recognition of cellular receptors by the mammalian reoviruses is an important determinant of cell and tissue tropism exhibited by reovirus strains of different serotypes. To extend our knowledge of the role of reovirus-receptor interactions in reovirus tropism, we determined whether type 1 and type 3 reovirus strains can infect cells derived from erythrocyte precursors. We found that reovirus type 3 Dearing (T3D), but not type 1 Lang, can grow in murine erythroleukemia (MEL) cells. This difference in growth was investigated by using reassortant viruses and we found that the capacity of T3D to infect MEL cells is determined by the viral cell-attachment protein, sigma 1. In experiments using murine monoclonal antibodies (mAbs) that bind to different sigma 1 regions, we show that T3D binding to MEL cells is inhibited by a mAb that identifies a domain important for hemagglutination (HA). We also determined that type 3 strains that can infect murine L cells but do not produce HA do not infect MEL cells. These results suggest that type 3 reovirus binds to and infects erythrocyte precursor cells via a sigma 1 domain important for HA. Moreover, this study suggests that different domains of some viral cell-attachment proteins are used to initiate productive infections of different types of cells."} {"id": "PMID:1281839", "title": "Loss of the common \"A\" determinant of hepatitis B surface antigen by a vaccine-induced escape mutant.", "content": "A previous study (Carman, W. F., A. R. Zanetti, P. Karayiannis, J. A. Waters, G. Manzillo, E. Tanzi, A. J. Zuckerman, and H. C. Thomas. 1990. Lancet. 336:325-329) demonstrated a variant hepatitis B surface antigen (HBsAg) in a vaccinated child born to a hepatitis B virus-infected mother. A substitution of arginine for glycine at amino acid 145 in HBsAg was observed. In this study the effect of this substitution on the common \"a\" determinant of this protein, against which protective immunity is directed, is investigated. Using recombinant HBsAg with and without the amino acid substitution, the binding of monoclonal antibodies that recognize different epitopes of the \"a\" determinant, was shown to be destroyed by the presence of arginine at amino acid 145. In convalescent and vaccinee sera, antibody binding to HBsAg was not inhibited by the variant HBsAg. Immunization with the variant HBsAg, although eliciting a high titer antibody that recognized the variant, produced a low titer of antibody recognizing the native protein. Studies in mice demonstrate that the immunogenicity of the variant protein is also substantially altered. The data presented here demonstrate that this variant evades the known protective anti-HBs response and lends support to the suggestion that this mutation arose as the result of immune pressure.", "contents": "Loss of the common \"A\" determinant of hepatitis B surface antigen by a vaccine-induced escape mutant. A previous study (Carman, W. F., A. R. Zanetti, P. Karayiannis, J. A. Waters, G. Manzillo, E. Tanzi, A. J. Zuckerman, and H. C. Thomas. 1990. Lancet. 336:325-329) demonstrated a variant hepatitis B surface antigen (HBsAg) in a vaccinated child born to a hepatitis B virus-infected mother. A substitution of arginine for glycine at amino acid 145 in HBsAg was observed. In this study the effect of this substitution on the common \"a\" determinant of this protein, against which protective immunity is directed, is investigated. Using recombinant HBsAg with and without the amino acid substitution, the binding of monoclonal antibodies that recognize different epitopes of the \"a\" determinant, was shown to be destroyed by the presence of arginine at amino acid 145. In convalescent and vaccinee sera, antibody binding to HBsAg was not inhibited by the variant HBsAg. Immunization with the variant HBsAg, although eliciting a high titer antibody that recognized the variant, produced a low titer of antibody recognizing the native protein. Studies in mice demonstrate that the immunogenicity of the variant protein is also substantially altered. The data presented here demonstrate that this variant evades the known protective anti-HBs response and lends support to the suggestion that this mutation arose as the result of immune pressure."} {"id": "PMID:1281840", "title": "Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis.", "content": "Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, is also secreted in peripheral inflammatory sites, where it acts as a local proinflammatory agent. Arthritis-susceptible LEW/N rats have profoundly deficient hypothalamic CRH responses to inflammatory stimuli and other stressors. Arthritis-resistant F344/N rats, on the other hand, have a robust increase in hypothalamic CRH in response to the same stimuli. Contrasting with these hypothalamic CRH responses, we now show that CRH expression is markedly increased in the joints and surrounding tissues of LEW/N rats with streptococcal cell wall- and adjuvant-induced arthritis, whereas it is not increased in similarly treated F344/N rats and is only transiently increased in congenitally athymic nude LEW.rnu/rnu rats. Glucocorticoid treatment suppressed, but did not eliminate, CRH immunoreactivity in the joints of LEW/N rats. CRH mRNA was present in inflamed synovia, as well as in spinal cord, and inflamed synovia also expressed specific CRH-binding sites. We compared CRH expression in inflamed joints with another well-characterized proinflammatory neuropeptide, substance P (SP), and found that SP immunoreactivity paralleled that of CRH. In summary, although LEW/N rats have deficient hypothalamic CRH responses to inflammatory stimuli compared with F344/N rats, they express relatively high levels of CRH at the site of inflammation. Analogous to SP, CRH may be delivered to the inflammatory site by peripheral nerves and/or synthesized at the inflammatory site. These data provide further support for the concept that CRH not only triggers the pituitary-adrenal antiinflammatory cascade, but also functions as an antithetically active local mediator of acute and chronic inflammatory arthritis. These data also illustrate the complex interrelationships of the nervous, endocrine, immune, and inflammatory systems.", "contents": "Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis. Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, is also secreted in peripheral inflammatory sites, where it acts as a local proinflammatory agent. Arthritis-susceptible LEW/N rats have profoundly deficient hypothalamic CRH responses to inflammatory stimuli and other stressors. Arthritis-resistant F344/N rats, on the other hand, have a robust increase in hypothalamic CRH in response to the same stimuli. Contrasting with these hypothalamic CRH responses, we now show that CRH expression is markedly increased in the joints and surrounding tissues of LEW/N rats with streptococcal cell wall- and adjuvant-induced arthritis, whereas it is not increased in similarly treated F344/N rats and is only transiently increased in congenitally athymic nude LEW.rnu/rnu rats. Glucocorticoid treatment suppressed, but did not eliminate, CRH immunoreactivity in the joints of LEW/N rats. CRH mRNA was present in inflamed synovia, as well as in spinal cord, and inflamed synovia also expressed specific CRH-binding sites. We compared CRH expression in inflamed joints with another well-characterized proinflammatory neuropeptide, substance P (SP), and found that SP immunoreactivity paralleled that of CRH. In summary, although LEW/N rats have deficient hypothalamic CRH responses to inflammatory stimuli compared with F344/N rats, they express relatively high levels of CRH at the site of inflammation. Analogous to SP, CRH may be delivered to the inflammatory site by peripheral nerves and/or synthesized at the inflammatory site. These data provide further support for the concept that CRH not only triggers the pituitary-adrenal antiinflammatory cascade, but also functions as an antithetically active local mediator of acute and chronic inflammatory arthritis. These data also illustrate the complex interrelationships of the nervous, endocrine, immune, and inflammatory systems."} {"id": "PMID:1281841", "title": "Can \"big\" insulin-like growth factor II in serum of tumor patients account for the development of extrapancreatic tumor hypoglycemia?", "content": "The pathogenesis of extrapancreatic tumor hypoglycemia has been related to the secretion of big insulin-like growth factor (IGF) II by the tumor. In 25 of 28 patients with this type of hypoglycemia we found 1.5-8-fold elevated serum levels of immunoreactive big (15-25 kD), but decreased levels of normal IGF II. After removal of the tumor, big IGF II disappeared and normal IGF II increased. Tumors contained elevated levels of IGF II, 65-80% in the big form. The insulin-like bioactivity of big IGF II and its affinity towards IGF-binding proteins (IGFBP)-2 and -3 are similar to those of normal IGF II, but two- to threefold higher on a molar basis. Big IGF II is mainly bound to the 50-kD IGFBP complex. The latter contains approximately 10 times more of this peptide than in normal serum and displays three- to fourfold increased insulin-like bioactivity. The formation of the 150-kD IGFBP complex with 125I-recombinant human IGFBP-3 is impaired in tumor serum. This results in sequestration of IGFBP-3 and predominant association of big IGF II with IGFBP-2 and -3 in the 50-kD complex. Increased bioavailability of big IGF II in this complex due to unrestricted capillary passage and enhanced insulin bioactivity of this big IGF II pool provide a continuous increased insulin-like potential available to insulin and type 1 IGF receptors of insulin-sensitive tissues and thus may lead to sustained hypoglycemia.", "contents": "Can \"big\" insulin-like growth factor II in serum of tumor patients account for the development of extrapancreatic tumor hypoglycemia? The pathogenesis of extrapancreatic tumor hypoglycemia has been related to the secretion of big insulin-like growth factor (IGF) II by the tumor. In 25 of 28 patients with this type of hypoglycemia we found 1.5-8-fold elevated serum levels of immunoreactive big (15-25 kD), but decreased levels of normal IGF II. After removal of the tumor, big IGF II disappeared and normal IGF II increased. Tumors contained elevated levels of IGF II, 65-80% in the big form. The insulin-like bioactivity of big IGF II and its affinity towards IGF-binding proteins (IGFBP)-2 and -3 are similar to those of normal IGF II, but two- to threefold higher on a molar basis. Big IGF II is mainly bound to the 50-kD IGFBP complex. The latter contains approximately 10 times more of this peptide than in normal serum and displays three- to fourfold increased insulin-like bioactivity. The formation of the 150-kD IGFBP complex with 125I-recombinant human IGFBP-3 is impaired in tumor serum. This results in sequestration of IGFBP-3 and predominant association of big IGF II with IGFBP-2 and -3 in the 50-kD complex. Increased bioavailability of big IGF II in this complex due to unrestricted capillary passage and enhanced insulin bioactivity of this big IGF II pool provide a continuous increased insulin-like potential available to insulin and type 1 IGF receptors of insulin-sensitive tissues and thus may lead to sustained hypoglycemia."} {"id": "PMID:1281842", "title": "In vivo retroviral gene transfer into human bronchial epithelia of xenografts.", "content": "Cystic fibrosis (CF) is the most common lethal inherited disease in the Caucasian population with an incidence of approximately 1 in 2,500 live births. Pulmonary complications of CF, which are the most morbid aspects of the disease, are caused by primary abnormalities in epithelial cells that lead to impaired mucociliary clearance. One potential therapeutic strategy is to reconstitute expression of the CF gene in airway epithelia by somatic gene transfer. To this end, we have developed an animal model of the human airway using bronchial xenografts and have tested the efficiency of in vivo retroviral gene transfer. Using the LacZ reporter gene, we find the efficiency of in vivo retroviral gene transfer to be dramatically dependent on the regenerative and mitotic state of the epithelium. Within an undifferentiated regenerating epithelium in which 40% of nuclei labeled with BrdU, 5-10% retroviral gene transfer was obtained. In contrast, no gene transfer was noted in a fully differentiated epithelium in which 1% of nuclei labeled with BrdU. These findings suggest that retroviral mediated gene transfer to the airway in vivo may be feasible if the proper regenerative state can be induced.", "contents": "In vivo retroviral gene transfer into human bronchial epithelia of xenografts. Cystic fibrosis (CF) is the most common lethal inherited disease in the Caucasian population with an incidence of approximately 1 in 2,500 live births. Pulmonary complications of CF, which are the most morbid aspects of the disease, are caused by primary abnormalities in epithelial cells that lead to impaired mucociliary clearance. One potential therapeutic strategy is to reconstitute expression of the CF gene in airway epithelia by somatic gene transfer. To this end, we have developed an animal model of the human airway using bronchial xenografts and have tested the efficiency of in vivo retroviral gene transfer. Using the LacZ reporter gene, we find the efficiency of in vivo retroviral gene transfer to be dramatically dependent on the regenerative and mitotic state of the epithelium. Within an undifferentiated regenerating epithelium in which 40% of nuclei labeled with BrdU, 5-10% retroviral gene transfer was obtained. In contrast, no gene transfer was noted in a fully differentiated epithelium in which 1% of nuclei labeled with BrdU. These findings suggest that retroviral mediated gene transfer to the airway in vivo may be feasible if the proper regenerative state can be induced."} {"id": "PMID:1281843", "title": "Giant neurons in the caudal pontine reticular formation receive short latency acoustic input: an intracellular recording and HRP-study in the rat.", "content": "The reticular formation is composed of heterogeneous cell populations with multiple functions. Among these multiple functions is the processing of sensory information in the context of behavior. The purpose of the present study was to identify and characterize neurons in the reticular formation of the rat that receive auditory input. In order to do so, we combined intracellular electrophysiology in vivo with intracellular injection of horseradish peroxidase, enabling us to correlate electrophysiology unequivocally with anatomy at the single cell level. We found that many neurons in the caudal pontine reticular nucleus (PnC), which we analyzed intracellularly, responded to acoustic stimuli and were excited at short latency (mean EPSP latency: 2.6 ms; mean spike latency: 5.2 ms). This short latency suggests a direct input from the cochlear nucleus, the first central nucleus of the auditory pathway. The morphology revealed that the acoustically driven PnC neurons have very large somata (mean diameter: 44.0 microns). They can therefore be referred to as \"giant PnC neurons.\" Complex dendritic arbors extended from these neurons into the reticular formation and thus formed a large membrane surface for the integration of multimodal inputs. Most of the giant PnC neurons sent their axons caudally into the medial longitudinal fasciculus and can therefore be regarded as reticulospinal neurons. The results demonstrate that the giant reticulospinal PnC neurons are in a position to transmit acoustic information very quickly to spinal cord neurons and to receive converging input from other parts of the brain. They are thus good candidates for participation in the mediation and modulation of acoustically elicited behaviors, such as the short latency acoustic startle response.", "contents": "Giant neurons in the caudal pontine reticular formation receive short latency acoustic input: an intracellular recording and HRP-study in the rat. The reticular formation is composed of heterogeneous cell populations with multiple functions. Among these multiple functions is the processing of sensory information in the context of behavior. The purpose of the present study was to identify and characterize neurons in the reticular formation of the rat that receive auditory input. In order to do so, we combined intracellular electrophysiology in vivo with intracellular injection of horseradish peroxidase, enabling us to correlate electrophysiology unequivocally with anatomy at the single cell level. We found that many neurons in the caudal pontine reticular nucleus (PnC), which we analyzed intracellularly, responded to acoustic stimuli and were excited at short latency (mean EPSP latency: 2.6 ms; mean spike latency: 5.2 ms). This short latency suggests a direct input from the cochlear nucleus, the first central nucleus of the auditory pathway. The morphology revealed that the acoustically driven PnC neurons have very large somata (mean diameter: 44.0 microns). They can therefore be referred to as \"giant PnC neurons.\" Complex dendritic arbors extended from these neurons into the reticular formation and thus formed a large membrane surface for the integration of multimodal inputs. Most of the giant PnC neurons sent their axons caudally into the medial longitudinal fasciculus and can therefore be regarded as reticulospinal neurons. The results demonstrate that the giant reticulospinal PnC neurons are in a position to transmit acoustic information very quickly to spinal cord neurons and to receive converging input from other parts of the brain. They are thus good candidates for participation in the mediation and modulation of acoustically elicited behaviors, such as the short latency acoustic startle response."} {"id": "PMID:1281844", "title": "Pattern of substance P- and cholecystokinin-like immunoreactivity during regeneration of the neural complex in the ascidian Ciona intestinalis.", "content": "The neural ganglion of ascidians exhibits a novel and rapid pattern of regeneration whereby within approximately 28-35 days of total ablation an entirely new neural complex is formed. In normal adults, neuronal cell bodies expressing substance P- (SP-Li), neurokinin A-(NKA-Li), CCK/gastrin- (CCK-Li), and insulin-like immunoreactivity exhibit a clearly defined pattern of localization in the cortical rind of the ganglion with characteristic long processes arising from the perikarya running throughout the neuropile. CCK-Li cell bodies are particularly concentrated close to the points of exit of the main nerve trunks. We have used antisera raised against these peptides to monitor the process of regeneration up to postoperative (pa) day 35. Only SP and CCK antisera produced positive staining in the regenerating tissue. Immunoreactive cell bodies first appear following 14 days pa. At this time CCK-Li neurons are more abundant than SP-Li neurons and in contrast to the pattern found in the normal adult ganglion, immunoreactive cell bodies are located both peripherally and centrally in the core of the ganglion and processes were rarely seen. Later stages exhibited an increasing number of SP-Li neurons and at 35 days pa SP-Li cell bodies clearly predominate. CCK-Li neurons typically become clustered close to the points of emergence of the anterior nerve roots. The early expression of CCK-Li and SP-Li molecules during regeneration is considered in terms of their potential role in development and cell proliferation in the newly forming ganglion.", "contents": "Pattern of substance P- and cholecystokinin-like immunoreactivity during regeneration of the neural complex in the ascidian Ciona intestinalis. The neural ganglion of ascidians exhibits a novel and rapid pattern of regeneration whereby within approximately 28-35 days of total ablation an entirely new neural complex is formed. In normal adults, neuronal cell bodies expressing substance P- (SP-Li), neurokinin A-(NKA-Li), CCK/gastrin- (CCK-Li), and insulin-like immunoreactivity exhibit a clearly defined pattern of localization in the cortical rind of the ganglion with characteristic long processes arising from the perikarya running throughout the neuropile. CCK-Li cell bodies are particularly concentrated close to the points of exit of the main nerve trunks. We have used antisera raised against these peptides to monitor the process of regeneration up to postoperative (pa) day 35. Only SP and CCK antisera produced positive staining in the regenerating tissue. Immunoreactive cell bodies first appear following 14 days pa. At this time CCK-Li neurons are more abundant than SP-Li neurons and in contrast to the pattern found in the normal adult ganglion, immunoreactive cell bodies are located both peripherally and centrally in the core of the ganglion and processes were rarely seen. Later stages exhibited an increasing number of SP-Li neurons and at 35 days pa SP-Li cell bodies clearly predominate. CCK-Li neurons typically become clustered close to the points of emergence of the anterior nerve roots. The early expression of CCK-Li and SP-Li molecules during regeneration is considered in terms of their potential role in development and cell proliferation in the newly forming ganglion."} {"id": "PMID:1281845", "title": "Cortico-cortical connections and cytoarchitectonics of the primate vestibular cortex: a study in squirrel monkeys (Saimiri sciureus).", "content": "The cortical connections of two vestibular fields [parieto-insular vestibular cortex (PIVC) and area 3aV] were studied in the squirrel monkey (Saimiri sciureus) by means of retrograde tracer techniques. Small iontophoretic or pressure injections of horseradish peroxidase (HRP), wheat-germ-HRP, Nuclear Yellow, and Fast Blue were administered to the cytoarchitectonic areas Ri (PIVC), 3aV, the parieto-temporal association area T3, the granular insula (Ig), and the rostral part of area 7 (7ant). The injection sites were physiologically characterized by means of microelectrode recordings and vestibular, optokinetic, or somatosensory stimulation: Area Ri is the region of the parieto-insular vestibular cortex (PIVC) as defined in macaques. The neck-trunk region of area 3a (area 3aV) also contains many neurons responding to stimulation of semicircular canal receptors. Some neurons of area T3 bordering on the PIVC also receive vestibular signals, but most neurons in area T3 responded preferentially to large-field optokinetic stimulation and not to vestibular stimulation. In none of the areas mentioned were responses to otolith stimulation found. The PIVC receives inputs from frontal and parietal cortical areas, especially areas 8a, 6, 3a, 3aV, 2, and 7ant. Area T3 receives signals from the insular and retroinsular cortex, various parts of area 7, visual areas of the parieto-occipital and parieto-temporal regions (area 19) and from a sector of the upper bank of the temporal sulcus (STS-area). The cortical afferents to area 3aV stem from areas 24, 4, 6, 7ant, from other parts of the primary somatosensory cortex, the secondary somatosensory cortex (SII), the retroinsular cortex (Ri), and the granular insula (Ig). In the border region of the areas 2 and 7ant, labelled neurons appeared after injections into both the PIVC and the area 3aV. This region is presumably the homologue to the vestibular area 2v of the macaque brain. In all regions cells within the contralateral cortex were less frequently labelled than cells in the homologous structures of the ipsilateral hemisphere. The cortical system for processing vestibular information about head-in-space movement consists mainly of the reciprocally interconnected areas PIVC and 3aV, and most likely of border regions of area 2 and 7ant. This \"inner cortical vestibular circuit\" also receives signals from two other cortical sensory systems, the somatosensory-proprioceptive system mediated by the primary somatosensory cortex and the visual movement system (optokinetic or visual flow signals). These visual movement signals reach PIVC via area 19 and area T3.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Cortico-cortical connections and cytoarchitectonics of the primate vestibular cortex: a study in squirrel monkeys (Saimiri sciureus). The cortical connections of two vestibular fields [parieto-insular vestibular cortex (PIVC) and area 3aV] were studied in the squirrel monkey (Saimiri sciureus) by means of retrograde tracer techniques. Small iontophoretic or pressure injections of horseradish peroxidase (HRP), wheat-germ-HRP, Nuclear Yellow, and Fast Blue were administered to the cytoarchitectonic areas Ri (PIVC), 3aV, the parieto-temporal association area T3, the granular insula (Ig), and the rostral part of area 7 (7ant). The injection sites were physiologically characterized by means of microelectrode recordings and vestibular, optokinetic, or somatosensory stimulation: Area Ri is the region of the parieto-insular vestibular cortex (PIVC) as defined in macaques. The neck-trunk region of area 3a (area 3aV) also contains many neurons responding to stimulation of semicircular canal receptors. Some neurons of area T3 bordering on the PIVC also receive vestibular signals, but most neurons in area T3 responded preferentially to large-field optokinetic stimulation and not to vestibular stimulation. In none of the areas mentioned were responses to otolith stimulation found. The PIVC receives inputs from frontal and parietal cortical areas, especially areas 8a, 6, 3a, 3aV, 2, and 7ant. Area T3 receives signals from the insular and retroinsular cortex, various parts of area 7, visual areas of the parieto-occipital and parieto-temporal regions (area 19) and from a sector of the upper bank of the temporal sulcus (STS-area). The cortical afferents to area 3aV stem from areas 24, 4, 6, 7ant, from other parts of the primary somatosensory cortex, the secondary somatosensory cortex (SII), the retroinsular cortex (Ri), and the granular insula (Ig). In the border region of the areas 2 and 7ant, labelled neurons appeared after injections into both the PIVC and the area 3aV. This region is presumably the homologue to the vestibular area 2v of the macaque brain. In all regions cells within the contralateral cortex were less frequently labelled than cells in the homologous structures of the ipsilateral hemisphere. The cortical system for processing vestibular information about head-in-space movement consists mainly of the reciprocally interconnected areas PIVC and 3aV, and most likely of border regions of area 2 and 7ant. This \"inner cortical vestibular circuit\" also receives signals from two other cortical sensory systems, the somatosensory-proprioceptive system mediated by the primary somatosensory cortex and the visual movement system (optokinetic or visual flow signals). These visual movement signals reach PIVC via area 19 and area T3.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281846", "title": "Innervation from the claustrum of the frontal association and motor areas: axonal transport studies in the cat.", "content": "The anatomical organization of the projections from the claustrum to the motor and prefrontal cortical areas of the cat's brain was investigated. Both retrograde (single horseradish peroxidase or double fluorochrome deposits in the cortex) and anterograde (peroxidase-labeled wheat germ agglutinin deposits in the claustrum) tracing techniques were used. Within the claustrum, the neurons projecting to each sector of the frontal cortex were found to be distributed according to specific patterns of segregation and overlap. Spatial segregation was particularly marked between the cell populations projecting to the various sectors of area 4. The cells projecting to the subareas of area 6 and prefrontal cortex displayed a less marked but definite segregation. The neuronal populations projecting to some sectors of areas 4, 5, and the primary somatosensory cortex known to contain homotopical representations of the body map were found intermingled in the same small claustral portions. The few double-labeled neurons found after closely adjacent fluorochrome injections indicates that, in spite of their profuse intracortical branching, claustral axons spread little within the boundaries of a single architectonic area. Anterograde transport experiments showed that claustral fibers end primarily in layers IIIb/IV, VI, and I, whereas layer V is spared. This pattern is homogeneous throughout the frontal cortex. The possible role of the claustrum as a subcortical site for organized interactions amongst wide arrays of functionally related zones of the cerebral cortex is thereby suggested.", "contents": "Innervation from the claustrum of the frontal association and motor areas: axonal transport studies in the cat. The anatomical organization of the projections from the claustrum to the motor and prefrontal cortical areas of the cat's brain was investigated. Both retrograde (single horseradish peroxidase or double fluorochrome deposits in the cortex) and anterograde (peroxidase-labeled wheat germ agglutinin deposits in the claustrum) tracing techniques were used. Within the claustrum, the neurons projecting to each sector of the frontal cortex were found to be distributed according to specific patterns of segregation and overlap. Spatial segregation was particularly marked between the cell populations projecting to the various sectors of area 4. The cells projecting to the subareas of area 6 and prefrontal cortex displayed a less marked but definite segregation. The neuronal populations projecting to some sectors of areas 4, 5, and the primary somatosensory cortex known to contain homotopical representations of the body map were found intermingled in the same small claustral portions. The few double-labeled neurons found after closely adjacent fluorochrome injections indicates that, in spite of their profuse intracortical branching, claustral axons spread little within the boundaries of a single architectonic area. Anterograde transport experiments showed that claustral fibers end primarily in layers IIIb/IV, VI, and I, whereas layer V is spared. This pattern is homogeneous throughout the frontal cortex. The possible role of the claustrum as a subcortical site for organized interactions amongst wide arrays of functionally related zones of the cerebral cortex is thereby suggested."} {"id": "PMID:1281847", "title": "Relationships between plasma composition and parotid salivary composition and secretion rates in the potoroine marsupials, Aepyprymnus rufescens and Potorous tridactylus.", "content": "Parotid salivation was investigated in two species of potoroine marsupial, Aepyprymnus rufescens and Potorous tridactylus to ascertain flow rates and composition, the buffer capacity of the saliva with respect to possible dependence of these animals on foregut fermentation, and the similarity of anion excretion patterns to those of the kangaroo parotid. Under anaesthesia neither species secreted spontaneously and secretion was stimulated by intravenous infusion of carbachol, bethanechol and isoprenaline. Under cholinergic stimulation in Aepyprymnus, the concentrations of Na, Cl, HCO3 and osmolality were positively correlated with flow rate, whereas K, Mg, PO4, H+ and urea were negatively correlated with flow. Amylase activity and the concentrations of protein and Ca showed no consistent relation to flow. Relative to Aepyprymnus, saliva of Potorous had much lower amylase activity and amylase activity per gram protein, lower concentrations of urea and Ca, and higher Na. Protein, K and HCO3 concentrations were similar in both species. The plasma of both species had similar electrolyte concentrations, but Potorous had lower protein, urea, osmolality and amylase activity. Plasma amylase activity in Aepyprymnus rose during cholinergic stimulation to levels in excess of rodent plasma. Isoprenaline infusion in Aepyprymnus increased salivary amylase activity and concentrations of protein, Ca, HCO3 and PO4, and reduced the concentrations of Cl and H+. The patterns of anion excretion in the two potoroine marsupials were dissimilar to those of the kangaroo parotid suggesting that parotid fluid secretion is not HCO3 driven to the same extent as that of Kangaroos. Buffer anion concentrations and secretion rates were similar to koalas and low relative to kangaroos, indicating that these potoroines do not rely on foregut fermentation.", "contents": "Relationships between plasma composition and parotid salivary composition and secretion rates in the potoroine marsupials, Aepyprymnus rufescens and Potorous tridactylus. Parotid salivation was investigated in two species of potoroine marsupial, Aepyprymnus rufescens and Potorous tridactylus to ascertain flow rates and composition, the buffer capacity of the saliva with respect to possible dependence of these animals on foregut fermentation, and the similarity of anion excretion patterns to those of the kangaroo parotid. Under anaesthesia neither species secreted spontaneously and secretion was stimulated by intravenous infusion of carbachol, bethanechol and isoprenaline. Under cholinergic stimulation in Aepyprymnus, the concentrations of Na, Cl, HCO3 and osmolality were positively correlated with flow rate, whereas K, Mg, PO4, H+ and urea were negatively correlated with flow. Amylase activity and the concentrations of protein and Ca showed no consistent relation to flow. Relative to Aepyprymnus, saliva of Potorous had much lower amylase activity and amylase activity per gram protein, lower concentrations of urea and Ca, and higher Na. Protein, K and HCO3 concentrations were similar in both species. The plasma of both species had similar electrolyte concentrations, but Potorous had lower protein, urea, osmolality and amylase activity. Plasma amylase activity in Aepyprymnus rose during cholinergic stimulation to levels in excess of rodent plasma. Isoprenaline infusion in Aepyprymnus increased salivary amylase activity and concentrations of protein, Ca, HCO3 and PO4, and reduced the concentrations of Cl and H+. The patterns of anion excretion in the two potoroine marsupials were dissimilar to those of the kangaroo parotid suggesting that parotid fluid secretion is not HCO3 driven to the same extent as that of Kangaroos. Buffer anion concentrations and secretion rates were similar to koalas and low relative to kangaroos, indicating that these potoroines do not rely on foregut fermentation."} {"id": "PMID:1281848", "title": "A narrow range, medium molecular weight pentastarch reduces structural organ damage in a hyperdynamic porcine model of sepsis.", "content": "to compare diafiltered 6% pentastarch (Pentafraction--PDP, MWn 120,000 and MWw 280,000) and native pentastarch (Pentaspan--PSP, MWn 63,000 and MWw 264,000 dalton) in a porcine model of faecal peritonitis. Randomised prospective study in 12 adolescent pigs. Prior to infection the study solution was infused to increase Qt by 25%. Thereafter adjustments in infusion rate were made (up to 1 l/h) in an attempt to maintain Qt at 25% above baseline values. Animals were sacrificed at 8 h. Tissue was excised from the right lobe of liver and from the right lung and fixed for later electron microscopy and digital morphometric analysis. Patent sinusoidal lumen was significantly greater in group PDP compared to PSP (11.3% +/- 2.3% of liver tissue versus 4.8% +/- 1.1%, p < 0.05) and this was accounted for by a significantly lower proportion of sinusoidal lumen occluded with white cells (2.1% +/- 0.6% versus 6.6% +/- 1.9%, p < 0.05). Similarly, patent capillary represented a significantly higher proportion of lung tissue for group PDP versus PSP (26.2% +/- 1.9% versus 18.5% +/- 2.7%, p < 0.05). The arithmetic mean alveolar capillary barrier thickness was significantly greater in group PSP than in group PDP (4.3 +/- 0.3 microns versus 2.5 +/- 0.3 microns, p < 0.01). The molecular weight profile of Pentafraction was associated with less structural organ damage including less tissue oedema and less white cell occlusion.", "contents": "A narrow range, medium molecular weight pentastarch reduces structural organ damage in a hyperdynamic porcine model of sepsis. to compare diafiltered 6% pentastarch (Pentafraction--PDP, MWn 120,000 and MWw 280,000) and native pentastarch (Pentaspan--PSP, MWn 63,000 and MWw 264,000 dalton) in a porcine model of faecal peritonitis. Randomised prospective study in 12 adolescent pigs. Prior to infection the study solution was infused to increase Qt by 25%. Thereafter adjustments in infusion rate were made (up to 1 l/h) in an attempt to maintain Qt at 25% above baseline values. Animals were sacrificed at 8 h. Tissue was excised from the right lobe of liver and from the right lung and fixed for later electron microscopy and digital morphometric analysis. Patent sinusoidal lumen was significantly greater in group PDP compared to PSP (11.3% +/- 2.3% of liver tissue versus 4.8% +/- 1.1%, p < 0.05) and this was accounted for by a significantly lower proportion of sinusoidal lumen occluded with white cells (2.1% +/- 0.6% versus 6.6% +/- 1.9%, p < 0.05). Similarly, patent capillary represented a significantly higher proportion of lung tissue for group PDP versus PSP (26.2% +/- 1.9% versus 18.5% +/- 2.7%, p < 0.05). The arithmetic mean alveolar capillary barrier thickness was significantly greater in group PSP than in group PDP (4.3 +/- 0.3 microns versus 2.5 +/- 0.3 microns, p < 0.01). The molecular weight profile of Pentafraction was associated with less structural organ damage including less tissue oedema and less white cell occlusion."} {"id": "PMID:1281849", "title": "Effects of aprotinin on hemorrhagic complications in ARDS patients during prolonged extracorporeal CO2 removal.", "content": "The effects of aprotinin, a broad-based proteinase inhibitor, in the management of hemorrhagic complications during prolonged venovenous extracorporeal CO2 removal in patients with adult respiratory distress syndrome are not evaluated. In two patients, aprotinin infusion was added to heparin to treat bleeding, occurring after few days of bypass and responsible for respiratory and hemodynamic deterioration. After aprotinin infusion (loading dose of 2 x 10(6) kIU followed by a continuous infusion of 5 x 10(5) kIU/h) combined with heparin, bleeding vanished until the end of bypass.", "contents": "Effects of aprotinin on hemorrhagic complications in ARDS patients during prolonged extracorporeal CO2 removal. The effects of aprotinin, a broad-based proteinase inhibitor, in the management of hemorrhagic complications during prolonged venovenous extracorporeal CO2 removal in patients with adult respiratory distress syndrome are not evaluated. In two patients, aprotinin infusion was added to heparin to treat bleeding, occurring after few days of bypass and responsible for respiratory and hemodynamic deterioration. After aprotinin infusion (loading dose of 2 x 10(6) kIU followed by a continuous infusion of 5 x 10(5) kIU/h) combined with heparin, bleeding vanished until the end of bypass."} {"id": "PMID:1281850", "title": "[Abdominal ectopic pregnancy. Limits of laparoscopic treatment].", "content": "We report a case of early abdominal pregnancy (6 weeks amenorrhea). The diagnosis of ectopic pregnancy was suspected according to the usual clinical, serologic, and sonographic procedure. It was confirmed by laparoscopy. Laparoscopic surgery was unable to assess the trophoblastic site and the hemostasis of the lesion that was histologically proven.", "contents": "[Abdominal ectopic pregnancy. Limits of laparoscopic treatment]. We report a case of early abdominal pregnancy (6 weeks amenorrhea). The diagnosis of ectopic pregnancy was suspected according to the usual clinical, serologic, and sonographic procedure. It was confirmed by laparoscopy. Laparoscopic surgery was unable to assess the trophoblastic site and the hemostasis of the lesion that was histologically proven."} {"id": "PMID:1281851", "title": "Partial seizures in two cases of metachromatic leukodystrophy: electrophysiologic and neuroradiologic findings.", "content": "This report concerns two cases of metachromatic leukodystrophy presenting partial seizures. One was a 2-year-old boy with a late infantile type and the other a 17-year-old girl with a juvenile type. The former had tonic-clonic seizures on the left with concomitant twitching of the left side of the face and adversive conjugate deviation of the eyes. After a while, his interictal sleep electroencephalogram (EEG) showed spikes in the right central area. The second case had hemiconvulsions on the right side, consisting mainly of tonic flexion of the upper limb followed by clonic flexions, and accompanied by adversive conjugate deviation of the head and eyes. Her ictal EEG showed rhythmic 6- to 7-Hz wave bursts in the left frontal area. To this date, no report has given a detailed discussion of the type of seizures and ictal EEG in metachromatic leukodystrophy. In addition, there have been few detailed reports of magnetic resonance imaging (MRI) in the juvenile type. It is interesting that typical partial seizures were observed in a hereditary metabolic disorder characterized by diffuse demyelination of the white matter, and the pathophysiology is discussed here mainly in relation to MRI findings of the case with the juvenile type.", "contents": "Partial seizures in two cases of metachromatic leukodystrophy: electrophysiologic and neuroradiologic findings. This report concerns two cases of metachromatic leukodystrophy presenting partial seizures. One was a 2-year-old boy with a late infantile type and the other a 17-year-old girl with a juvenile type. The former had tonic-clonic seizures on the left with concomitant twitching of the left side of the face and adversive conjugate deviation of the eyes. After a while, his interictal sleep electroencephalogram (EEG) showed spikes in the right central area. The second case had hemiconvulsions on the right side, consisting mainly of tonic flexion of the upper limb followed by clonic flexions, and accompanied by adversive conjugate deviation of the head and eyes. Her ictal EEG showed rhythmic 6- to 7-Hz wave bursts in the left frontal area. To this date, no report has given a detailed discussion of the type of seizures and ictal EEG in metachromatic leukodystrophy. In addition, there have been few detailed reports of magnetic resonance imaging (MRI) in the juvenile type. It is interesting that typical partial seizures were observed in a hereditary metabolic disorder characterized by diffuse demyelination of the white matter, and the pathophysiology is discussed here mainly in relation to MRI findings of the case with the juvenile type."} {"id": "PMID:1281852", "title": "A child with valproic acid-associated carnitine deficiency and carnitine-responsive cardiac dysfunction.", "content": "Valproic acid enhances renal losses of carnitine esters and leads to decreased plasma free carnitine concentrations in many patients receiving valproic acid therapy. However, decreased serum carnitine levels are of unclear pathologic significance, and most children manifest no symptoms of carnitine deficiency. We report a child with valproic acid-associated carnitine deficiency who had severe cardiac dysfunction develop that resolved with carnitine replacement therapy.", "contents": "A child with valproic acid-associated carnitine deficiency and carnitine-responsive cardiac dysfunction. Valproic acid enhances renal losses of carnitine esters and leads to decreased plasma free carnitine concentrations in many patients receiving valproic acid therapy. However, decreased serum carnitine levels are of unclear pathologic significance, and most children manifest no symptoms of carnitine deficiency. We report a child with valproic acid-associated carnitine deficiency who had severe cardiac dysfunction develop that resolved with carnitine replacement therapy."} {"id": "PMID:1281853", "title": "Molecular cloning of the cDNA encoding a 42 kDa antigenic polypeptide of Anisakis simplex larvae.", "content": "The gene encoding an antigenic polypeptide of Anisakis simplex larvae was studied using recombinant DNA techniques. cDNA synthesized from poly(A)-rich mRNA from A. simplex larvae was ligated into phage vector lambda gtll DNA and packaged in vitro. The phages were propagated on Escherichia coli and a lambda gtll expression library was constructed. A cDNA clone encoding a 42 kDa antigenic polypeptide was selected by immunoscreening of the library and identified by the epitope selection method. A clone containing cDNA for a 42 kDa protein was isolated. The gene encoding this 42 kDa antigenic polypeptide was characterized by DNA and RNA blot analysis using the cDNA as a probe. The gene was transcribed to mRNA with approximately 1400 nucleotides and translated to 42 kDa polypeptide. The antigenic beta-galactosidase fusion protein synthesized by bacteria had no cross-reactivity with other parasite-infected sera.", "contents": "Molecular cloning of the cDNA encoding a 42 kDa antigenic polypeptide of Anisakis simplex larvae. The gene encoding an antigenic polypeptide of Anisakis simplex larvae was studied using recombinant DNA techniques. cDNA synthesized from poly(A)-rich mRNA from A. simplex larvae was ligated into phage vector lambda gtll DNA and packaged in vitro. The phages were propagated on Escherichia coli and a lambda gtll expression library was constructed. A cDNA clone encoding a 42 kDa antigenic polypeptide was selected by immunoscreening of the library and identified by the epitope selection method. A clone containing cDNA for a 42 kDa protein was isolated. The gene encoding this 42 kDa antigenic polypeptide was characterized by DNA and RNA blot analysis using the cDNA as a probe. The gene was transcribed to mRNA with approximately 1400 nucleotides and translated to 42 kDa polypeptide. The antigenic beta-galactosidase fusion protein synthesized by bacteria had no cross-reactivity with other parasite-infected sera."} {"id": "PMID:1281854", "title": "Trichinella spiralis: specificity of ES antigens from pre-encysted larvae.", "content": "Excretory/secretory (ES) antigens were obtained by culturing pre-encysted Trichinella spiralis larvae which were recovered from muscles of experimentally infected mice 14-15 days postinfection. Analyses of these antigens (PEL ES) with immunoblotting, SDS-PAGE and Triple Antibody ELISA showed that they yielded a low sensitivity and specificity when tested with antisera against the common nematodes of Chinese pigs. As compared to ES antigens from encysted larvae, PEL ES also contained more low molecular mass proteins.", "contents": "Trichinella spiralis: specificity of ES antigens from pre-encysted larvae. Excretory/secretory (ES) antigens were obtained by culturing pre-encysted Trichinella spiralis larvae which were recovered from muscles of experimentally infected mice 14-15 days postinfection. Analyses of these antigens (PEL ES) with immunoblotting, SDS-PAGE and Triple Antibody ELISA showed that they yielded a low sensitivity and specificity when tested with antisera against the common nematodes of Chinese pigs. As compared to ES antigens from encysted larvae, PEL ES also contained more low molecular mass proteins."} {"id": "PMID:1281855", "title": "Stage-specific expression of a developmentally regulated gene in Dirofilaria immitis.", "content": "A previously reported cDNA clone encoding 34 kDa antigenic polypeptide of Dirofilaria immitis (lambda cD34) was studied to elucidate the mechanism of stage-specific gene expression. The 34 kDa polypeptide was a larva-specific antigen and the mRNA was detectable in microfilariae but not in adult worms and eggs. The lambda cD34 gene was not sex linked and was contained in the genome of D. immitis at each stage. The stage-specific expression of the developmentally regulated gene in D. immitis may be controlled primarily at the mRNA level.", "contents": "Stage-specific expression of a developmentally regulated gene in Dirofilaria immitis. A previously reported cDNA clone encoding 34 kDa antigenic polypeptide of Dirofilaria immitis (lambda cD34) was studied to elucidate the mechanism of stage-specific gene expression. The 34 kDa polypeptide was a larva-specific antigen and the mRNA was detectable in microfilariae but not in adult worms and eggs. The lambda cD34 gene was not sex linked and was contained in the genome of D. immitis at each stage. The stage-specific expression of the developmentally regulated gene in D. immitis may be controlled primarily at the mRNA level."} {"id": "PMID:1281856", "title": "Spinal cord and ganglia regeneration in larval Xenopus laevis following unilateral ablation.", "content": "The experiments were carried out on larvae of Xenopus laevis at stage 48 (acc. to Nieuwkoop and Faber, 1956). Two different kinds of experiments were performed. Experiment I: Unilateral ablation of either a brachial or lumbar segment of the spinal cord and simultaneous removal of the related ganglia. Experiment II: Simple unilateral removal of either brachial or lumbar spinal ganglia. The results obtained in Experiment I show that not only an extensive restitution of the ablated spinal cord does take place, but the regeneration of spinal ganglia may also occur following migration of neural elements from the regenerating spinal cord. The medullary neuroblasts leave the spinal cord along two paths: i) through projections of the gray matter, probably due to the lack of an effective glia limitans; ii) through the motor fibers leaving the spinal cord to form the ventral roots. The first path is followed occasionally while the second is the one usually used when the ventral roots are present. Data based on animals injected with 5-bromodeoxyuridine and sacrificed at fixed intervals, suggest that ganglion precursors, as well as the medullary neurons and glia, originate in the ependyma. This conclusion is supported by the results of Experiment II which demonstrate that when the spinal cord is left intact no discrete groups of ganglion cells and/or glial cells are formed.", "contents": "Spinal cord and ganglia regeneration in larval Xenopus laevis following unilateral ablation. The experiments were carried out on larvae of Xenopus laevis at stage 48 (acc. to Nieuwkoop and Faber, 1956). Two different kinds of experiments were performed. Experiment I: Unilateral ablation of either a brachial or lumbar segment of the spinal cord and simultaneous removal of the related ganglia. Experiment II: Simple unilateral removal of either brachial or lumbar spinal ganglia. The results obtained in Experiment I show that not only an extensive restitution of the ablated spinal cord does take place, but the regeneration of spinal ganglia may also occur following migration of neural elements from the regenerating spinal cord. The medullary neuroblasts leave the spinal cord along two paths: i) through projections of the gray matter, probably due to the lack of an effective glia limitans; ii) through the motor fibers leaving the spinal cord to form the ventral roots. The first path is followed occasionally while the second is the one usually used when the ventral roots are present. Data based on animals injected with 5-bromodeoxyuridine and sacrificed at fixed intervals, suggest that ganglion precursors, as well as the medullary neurons and glia, originate in the ependyma. This conclusion is supported by the results of Experiment II which demonstrate that when the spinal cord is left intact no discrete groups of ganglion cells and/or glial cells are formed."} {"id": "PMID:1281857", "title": "GOLGI cells of the cerebellum of the dogfish, Scyliorhinus canicula (elasmobranchs): a GOLGI and ultrastructural study.", "content": "GOLGI cells of the dogfish cerebellum were studied using both GOLGI methods and electron microscopy. The arborization of their dendrites and axonal processes is limited to the granular layer, which in this species forms characteristic granular eminences. The dendrites are rather simple. However, the various axons of a GOLGI cell form a dense plexus of thin beaded processes whose complexity approaches that observed in the mammalian cerebellum. Electron microscopy shows that the GOLGI cells are medium-sized neurons whose processes contact cerebellar glomerulus of the granular layer. The GOLGI cell perikarya are also contacted by mossy fibres.", "contents": "GOLGI cells of the cerebellum of the dogfish, Scyliorhinus canicula (elasmobranchs): a GOLGI and ultrastructural study. GOLGI cells of the dogfish cerebellum were studied using both GOLGI methods and electron microscopy. The arborization of their dendrites and axonal processes is limited to the granular layer, which in this species forms characteristic granular eminences. The dendrites are rather simple. However, the various axons of a GOLGI cell form a dense plexus of thin beaded processes whose complexity approaches that observed in the mammalian cerebellum. Electron microscopy shows that the GOLGI cells are medium-sized neurons whose processes contact cerebellar glomerulus of the granular layer. The GOLGI cell perikarya are also contacted by mossy fibres."} {"id": "PMID:1281859", "title": "The two size alleles of human keratin 1 are due to a deletion in the glycine-rich carboxyl-terminal V2 subdomain.", "content": "Two size variants of the type II human keratin 1 protein chain, termed 1a and 1b, have been described previously. Using amplification of genomic DNA by the polymerase chain reaction and sequence analysis we show here that the difference between these two alleles is due to a deletion of 21 bp in sequences encoding the V2 subdomain. This deletion corresponds to an entire glycine loop of seven amino acids. Pedigree analysis showed that the alleles are inherited as normal Mendelian traits. No additional alleles were detected in a survey of 88 alleles from 44 unrelated individuals, and the allelic frequency of 1a and 1b was 0.61 and 0.39. To determine the molecular basis of inherited dermatoses it is preferable to perform genetic linkage studies utilizing candidate genes directly as polymorphic markers. The PCR-based keratin 1 alleles characterized here, together with previously described PCR-based size variants in the keratin 10 gene, provide useful markers for the keratin clusters on chromosome 12 and 17, respectively.", "contents": "The two size alleles of human keratin 1 are due to a deletion in the glycine-rich carboxyl-terminal V2 subdomain. Two size variants of the type II human keratin 1 protein chain, termed 1a and 1b, have been described previously. Using amplification of genomic DNA by the polymerase chain reaction and sequence analysis we show here that the difference between these two alleles is due to a deletion of 21 bp in sequences encoding the V2 subdomain. This deletion corresponds to an entire glycine loop of seven amino acids. Pedigree analysis showed that the alleles are inherited as normal Mendelian traits. No additional alleles were detected in a survey of 88 alleles from 44 unrelated individuals, and the allelic frequency of 1a and 1b was 0.61 and 0.39. To determine the molecular basis of inherited dermatoses it is preferable to perform genetic linkage studies utilizing candidate genes directly as polymorphic markers. The PCR-based keratin 1 alleles characterized here, together with previously described PCR-based size variants in the keratin 10 gene, provide useful markers for the keratin clusters on chromosome 12 and 17, respectively."} {"id": "PMID:1281860", "title": "Expression and modulation of the vitronectin receptor on human dermal microvascular endothelial cells.", "content": "Microvascular endothelial cells express a variety of cell-surface integrins in vivo and in vitro with varying affinities for matrix proteins. The vitronectin receptor (VnR), a complex of the alpha v and beta 3 integrin chains, is capable of binding to a variety of matrix proteins that are deposited in injured tissues, including vitronectin, fibrinogen, and thrombin. Staining of frozen sections of human skin with antibodies recognizing the VnR and examination by immunofluorescence microscopy demonstrates staining in a vascular pattern suggesting in vivo expression of the vitronectin receptor on endothelial cells. Examination of pure cultures of human dermal microvascular endothelial cells (HDMEC) by flow-cytometric analysis and enzyme-linked immunosorbent assay confirmed that HDMEC also express cell surface VnR complex in vitro. Stimulation of human dermal microvascular endothelial cells in vitro with agents that stimulate protein kinase C resulted in dose- and time-dependent increases in expression of alpha v and beta 3 integrin chains. Additionally, stimulation with basic fibroblast growth factor induced similar increases, but stimulation with transforming growth factor-beta or interleukin-1 alpha failed to increase VnR expression. Increases in cell-surface VnR expression also correlated with an increased ability of microvascular endothelial cells to bind to vitronectin, but not fibronectin-coated surfaces. Although increases in cell-surface expression of beta 3 paralleled increases in expression of cell-surface alpha v, regulation of mRNA expression was distinct for each chain. These data suggests that microvascular endothelial cells express the VnR complex in vivo, that the cell-surface expression of this integrin on dermal microvascular endothelial cells can be regulated, and that this regulation may be important in cell adherence, cell migration, and wound healing.", "contents": "Expression and modulation of the vitronectin receptor on human dermal microvascular endothelial cells. Microvascular endothelial cells express a variety of cell-surface integrins in vivo and in vitro with varying affinities for matrix proteins. The vitronectin receptor (VnR), a complex of the alpha v and beta 3 integrin chains, is capable of binding to a variety of matrix proteins that are deposited in injured tissues, including vitronectin, fibrinogen, and thrombin. Staining of frozen sections of human skin with antibodies recognizing the VnR and examination by immunofluorescence microscopy demonstrates staining in a vascular pattern suggesting in vivo expression of the vitronectin receptor on endothelial cells. Examination of pure cultures of human dermal microvascular endothelial cells (HDMEC) by flow-cytometric analysis and enzyme-linked immunosorbent assay confirmed that HDMEC also express cell surface VnR complex in vitro. Stimulation of human dermal microvascular endothelial cells in vitro with agents that stimulate protein kinase C resulted in dose- and time-dependent increases in expression of alpha v and beta 3 integrin chains. Additionally, stimulation with basic fibroblast growth factor induced similar increases, but stimulation with transforming growth factor-beta or interleukin-1 alpha failed to increase VnR expression. Increases in cell-surface VnR expression also correlated with an increased ability of microvascular endothelial cells to bind to vitronectin, but not fibronectin-coated surfaces. Although increases in cell-surface expression of beta 3 paralleled increases in expression of cell-surface alpha v, regulation of mRNA expression was distinct for each chain. These data suggests that microvascular endothelial cells express the VnR complex in vivo, that the cell-surface expression of this integrin on dermal microvascular endothelial cells can be regulated, and that this regulation may be important in cell adherence, cell migration, and wound healing."} {"id": "PMID:1281861", "title": "Anti-inflammatory effect of FK-506 on human skin mast cells.", "content": "FK-506 and the structurally related macrolide rapamycin are high-affinity ligands for a specific binding protein (FK-506 binding protein). We examined the effects of FK-506 and rapamycin on the release of pre-formed (histamine) and de novo synthesized inflammatory mediators (prostaglandin D2) from mast cells isolated from human skin tissue. FK-506 (0.1 to 100 nM) concentration-dependently inhibited (5 to 65%) histamine release from skin mast cells activated by anti-IgE. FK-506 was more potent in skin mast cells than in basophils (IC40 = 2.15 +/- 0.78 nM versus 5.12 +/- 1.34 nM; p < 0.001), whereas the maximal inhibitory effect was higher in basophils than in skin mast cells (88.77 +/- 2.44% versus 67.30 +/- 3.98%; p < 0.01). FK-506 had little or no inhibitory effect on histamine release from skin mast cells challenged with compound A23187 and substance P, respectively, whereas it completely suppressed A23187-induced histamine release from basophils. FK-506 (0.1 to 100 nM) also inhibited (up to 65%) the de novo synthesis of prostaglandin D2 from skin mast cells challenged with anti-IgE. Despite its structural similarity to FK-506, rapamycin (10 to 300 nM) had little or no effect on the release of histamine from skin mast cells induced by anti-IgE, A23187, and substance P. However, rapamycin competitively antagonized the inhibitory effect of FK-506 on anti-IgE-induced histamine release from skin mast cells with a dissociation constant of about 14 nM. These data indicate that FK-506, but not rapamycin, is a potent anti-inflammatory agent acting on skin mast cells presumably by binding to the FK-506 binding protein. It thus appears that binding to the FK-506 binding protein is necessary, but not sufficient, to deliver an inhibitory signal to skin mast cells.", "contents": "Anti-inflammatory effect of FK-506 on human skin mast cells. FK-506 and the structurally related macrolide rapamycin are high-affinity ligands for a specific binding protein (FK-506 binding protein). We examined the effects of FK-506 and rapamycin on the release of pre-formed (histamine) and de novo synthesized inflammatory mediators (prostaglandin D2) from mast cells isolated from human skin tissue. FK-506 (0.1 to 100 nM) concentration-dependently inhibited (5 to 65%) histamine release from skin mast cells activated by anti-IgE. FK-506 was more potent in skin mast cells than in basophils (IC40 = 2.15 +/- 0.78 nM versus 5.12 +/- 1.34 nM; p < 0.001), whereas the maximal inhibitory effect was higher in basophils than in skin mast cells (88.77 +/- 2.44% versus 67.30 +/- 3.98%; p < 0.01). FK-506 had little or no inhibitory effect on histamine release from skin mast cells challenged with compound A23187 and substance P, respectively, whereas it completely suppressed A23187-induced histamine release from basophils. FK-506 (0.1 to 100 nM) also inhibited (up to 65%) the de novo synthesis of prostaglandin D2 from skin mast cells challenged with anti-IgE. Despite its structural similarity to FK-506, rapamycin (10 to 300 nM) had little or no effect on the release of histamine from skin mast cells induced by anti-IgE, A23187, and substance P. However, rapamycin competitively antagonized the inhibitory effect of FK-506 on anti-IgE-induced histamine release from skin mast cells with a dissociation constant of about 14 nM. These data indicate that FK-506, but not rapamycin, is a potent anti-inflammatory agent acting on skin mast cells presumably by binding to the FK-506 binding protein. It thus appears that binding to the FK-506 binding protein is necessary, but not sufficient, to deliver an inhibitory signal to skin mast cells."} {"id": "PMID:1281862", "title": "Comparison of the effects of moist and dry conditions on the process of angiogenesis during dermal repair.", "content": "The effect of moist and dry conditions on the process of angiogenesis during dermal repair was investigated. The moist conditions were achieved by covering excised wounds on porcine flank skin with the adhesive polyurethane dressing Opsite and dry conditions were achieved by exposure to air through dry gauze dressings. Angiogenesis was assessed during the period from 3 to 60 d after injury. Quantitative studies, using computerized image analysis, were carried out on microfocal x-ray images of skin sections whose blood system had been perfused in vivo with a radio-opaque medium. The analytical technique yielded information with regard to vessel number per wound and also the area occupied by blood vessels per unit wound area. Three regions were assessed in each wound bed: upper zone, just below the surface of the wound; the lower zone, just above the base of the wound bed; and the middle zone, midway between the other two zones. The results showed that the wounds maintained in a moist environment revascularized at a greater rate than those maintained in a dry environment. This was apparent in all of the zones of the wound bed examined. The development of new vessels occurred in a more orderly manner in the moist wounds. There was an early increase in vessel number rising to a peak around days 3-5, then a gradual decrease in number starting around day 7. In contrast, in the dry wounds the development of blood vessels was less rapid. Peak vessel number in the upper zone was significantly less than that achieved in the moist wounds, and was not reached until 7 d after injury. The decrease in vessel number from the peak was less rapid in the dry wounds, suggesting that there was a delayed entry into the remodeling phase in comparison with the moist wounds. The results also showed that the total percentage area of the wound bed occupied by blood vessels was greater in the moist wounds than the dry wounds from 3 d after injury until day 7. This level of vascularization was maintained beyond 7 d after injury even when the vessel number in the moist wounds was significantly less than in the dry wounds, suggesting that the vessels in the moist wounds were larger and, presumably, more mature. In general, moist wounds showed a more rapid decline towards uninjured skin levels of vascularization than dry wounds.", "contents": "Comparison of the effects of moist and dry conditions on the process of angiogenesis during dermal repair. The effect of moist and dry conditions on the process of angiogenesis during dermal repair was investigated. The moist conditions were achieved by covering excised wounds on porcine flank skin with the adhesive polyurethane dressing Opsite and dry conditions were achieved by exposure to air through dry gauze dressings. Angiogenesis was assessed during the period from 3 to 60 d after injury. Quantitative studies, using computerized image analysis, were carried out on microfocal x-ray images of skin sections whose blood system had been perfused in vivo with a radio-opaque medium. The analytical technique yielded information with regard to vessel number per wound and also the area occupied by blood vessels per unit wound area. Three regions were assessed in each wound bed: upper zone, just below the surface of the wound; the lower zone, just above the base of the wound bed; and the middle zone, midway between the other two zones. The results showed that the wounds maintained in a moist environment revascularized at a greater rate than those maintained in a dry environment. This was apparent in all of the zones of the wound bed examined. The development of new vessels occurred in a more orderly manner in the moist wounds. There was an early increase in vessel number rising to a peak around days 3-5, then a gradual decrease in number starting around day 7. In contrast, in the dry wounds the development of blood vessels was less rapid. Peak vessel number in the upper zone was significantly less than that achieved in the moist wounds, and was not reached until 7 d after injury. The decrease in vessel number from the peak was less rapid in the dry wounds, suggesting that there was a delayed entry into the remodeling phase in comparison with the moist wounds. The results also showed that the total percentage area of the wound bed occupied by blood vessels was greater in the moist wounds than the dry wounds from 3 d after injury until day 7. This level of vascularization was maintained beyond 7 d after injury even when the vessel number in the moist wounds was significantly less than in the dry wounds, suggesting that the vessels in the moist wounds were larger and, presumably, more mature. In general, moist wounds showed a more rapid decline towards uninjured skin levels of vascularization than dry wounds."} {"id": "PMID:1281863", "title": "Expression of growth-associated protein 43 and nerve growth factor receptor in human skin: a comparative immunohistochemical investigation.", "content": "The growth-associated protein 43 (GAP43) is a neuronal membrane protein involved in axonal growth and regeneration as well as in the modulation of synaptic plasticity. It is present in sensory and sympathetic neurons, where it is consistently associated with the expression of nerve growth factor receptor (NGFr). We investigated, by means of immunohistochemistry, the presence and distribution of the GAP43-immunoreactivity (IR) and of the NGFr-IR in the adult normal human skin from various body regions. In adjacent sections, a comparison with the distribution of the neuronal markers protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-related peptide (CGRP) was performed. Our results indicate that in adult human skin 1) a GAP43-IR is morphologically present in epidermal and dermal nerve fibers; 2) a NGFr-IR is associated with neuronal as well as non-neuronal elements of cutaneous nerves; 3) the basal epidermal cell layer expresses a NGFr-IR, which is unevenly distributed according to the different body areas; and 4) there is suggestive evidence for a simultaneous expression of GAP43-, NGFr-, PGP 9.5-, SP-, and CGRP-IR in at least part of the cutaneous nerve fibers. The presence of GAP43-immunoreactive nerve fibers might be a marker of a continuous synaptic remodeling in adult skin, whereas the distribution of the NGFr-IR could be relevant for our understanding of the maintenance of the neuronal-target relationship(s).", "contents": "Expression of growth-associated protein 43 and nerve growth factor receptor in human skin: a comparative immunohistochemical investigation. The growth-associated protein 43 (GAP43) is a neuronal membrane protein involved in axonal growth and regeneration as well as in the modulation of synaptic plasticity. It is present in sensory and sympathetic neurons, where it is consistently associated with the expression of nerve growth factor receptor (NGFr). We investigated, by means of immunohistochemistry, the presence and distribution of the GAP43-immunoreactivity (IR) and of the NGFr-IR in the adult normal human skin from various body regions. In adjacent sections, a comparison with the distribution of the neuronal markers protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-related peptide (CGRP) was performed. Our results indicate that in adult human skin 1) a GAP43-IR is morphologically present in epidermal and dermal nerve fibers; 2) a NGFr-IR is associated with neuronal as well as non-neuronal elements of cutaneous nerves; 3) the basal epidermal cell layer expresses a NGFr-IR, which is unevenly distributed according to the different body areas; and 4) there is suggestive evidence for a simultaneous expression of GAP43-, NGFr-, PGP 9.5-, SP-, and CGRP-IR in at least part of the cutaneous nerve fibers. The presence of GAP43-immunoreactive nerve fibers might be a marker of a continuous synaptic remodeling in adult skin, whereas the distribution of the NGFr-IR could be relevant for our understanding of the maintenance of the neuronal-target relationship(s)."} {"id": "PMID:1281864", "title": "Keratinocytes and fibroblasts from a patient with mutilating dystrophic epidermolysis bullosa synthesize drastically reduced amounts of collagen VII: lack of effect of transforming growth factor-beta.", "content": "Keratinocytes and fibroblasts derived from skin of a patient with recessive dystrophic mutilating epidermolysis bullosa (EB) did not synthesize collagen VII as assessed by indirect immunofluorescence staining or immunoblotting, but expressed another basement membrane protein, laminin, in a normal manner. In contrast to control cells, no stimulation of collagen VII production was achieved in co-cultures of EB keratinocytes and fibroblasts. Further, treatment of normal keratinocytes or co-cultures with TGF-beta 2 significantly increased their expression of collagen VII, whereas the cytokine failed to induce its synthesis in the EB cells. Mixed co-cultures were constructed with normal fibroblasts and EB keratinocytes and vice versa. Both combinations showed strong expression of collagen VII in the normal cells but no synthesis in the EB counterparts. These results suggest that in this patient with severe mutilating dystrophic EB, inability of cutaneous cells to synthesize sufficient amounts of collagen VII underlies the lack of anchoring fibrils and skin fragility.", "contents": "Keratinocytes and fibroblasts from a patient with mutilating dystrophic epidermolysis bullosa synthesize drastically reduced amounts of collagen VII: lack of effect of transforming growth factor-beta. Keratinocytes and fibroblasts derived from skin of a patient with recessive dystrophic mutilating epidermolysis bullosa (EB) did not synthesize collagen VII as assessed by indirect immunofluorescence staining or immunoblotting, but expressed another basement membrane protein, laminin, in a normal manner. In contrast to control cells, no stimulation of collagen VII production was achieved in co-cultures of EB keratinocytes and fibroblasts. Further, treatment of normal keratinocytes or co-cultures with TGF-beta 2 significantly increased their expression of collagen VII, whereas the cytokine failed to induce its synthesis in the EB cells. Mixed co-cultures were constructed with normal fibroblasts and EB keratinocytes and vice versa. Both combinations showed strong expression of collagen VII in the normal cells but no synthesis in the EB counterparts. These results suggest that in this patient with severe mutilating dystrophic EB, inability of cutaneous cells to synthesize sufficient amounts of collagen VII underlies the lack of anchoring fibrils and skin fragility."} {"id": "PMID:1281865", "title": "Purification of immunoprecipitated pemphigus foliaceus antigen fragment and its use in radioimmunoassay.", "content": "A major difficulty in biochemical studies of the pemphigus foliaceus (PF) antigen is the lack of a method for its quantitative determination. Immunofluorescence blocking and immunoprecipitation methods are semiquantitative and time consuming. Radioimmunoassay (RIA) methods are quantitative but they require pure and stable antigen preparations that have not been available for PF. The present investigation shows the further purification of a previously described preparation of PF antigen fragment obtained from trypsinization media of mouse skin (Con A Frn) and demonstrates its usefulness in a RIA method for quantitation of the antigen. The major contaminants of the 45-kD tryptic fragment of the PF antigen (tf-PF) in immunoprecipitates of the Con A Frn with PF sera were identified as H and L chains of murine IgG and mannose-binding lectins. The IgG contaminants could be removed by avoidance of blood contamination during preparation of the Con A Frn and/or pre-absorption of the Con A Frn with protein A Sepharose. The lectins could be removed by affinity chromatography of the Con A Frn on asialofetuin column and washing the immunoprecipitates with 0.2 M alpha-methyl-mannoside. Using the purified, labeled Con A Frn in RIA, we showed that standard curves could be established and the amounts of PF antigen could be determined in different extracts without the need for electrophoresis, autoradiography, or scanning. This RIA method is rapid and can be easily used to analyze many samples, e.g., chromatographic fractions and extracts made from different tissues.", "contents": "Purification of immunoprecipitated pemphigus foliaceus antigen fragment and its use in radioimmunoassay. A major difficulty in biochemical studies of the pemphigus foliaceus (PF) antigen is the lack of a method for its quantitative determination. Immunofluorescence blocking and immunoprecipitation methods are semiquantitative and time consuming. Radioimmunoassay (RIA) methods are quantitative but they require pure and stable antigen preparations that have not been available for PF. The present investigation shows the further purification of a previously described preparation of PF antigen fragment obtained from trypsinization media of mouse skin (Con A Frn) and demonstrates its usefulness in a RIA method for quantitation of the antigen. The major contaminants of the 45-kD tryptic fragment of the PF antigen (tf-PF) in immunoprecipitates of the Con A Frn with PF sera were identified as H and L chains of murine IgG and mannose-binding lectins. The IgG contaminants could be removed by avoidance of blood contamination during preparation of the Con A Frn and/or pre-absorption of the Con A Frn with protein A Sepharose. The lectins could be removed by affinity chromatography of the Con A Frn on asialofetuin column and washing the immunoprecipitates with 0.2 M alpha-methyl-mannoside. Using the purified, labeled Con A Frn in RIA, we showed that standard curves could be established and the amounts of PF antigen could be determined in different extracts without the need for electrophoresis, autoradiography, or scanning. This RIA method is rapid and can be easily used to analyze many samples, e.g., chromatographic fractions and extracts made from different tissues."} {"id": "PMID:1281866", "title": "Abnormal lamellar granules in harlequin ichthyosis.", "content": "Lamellar granules are specialized lipid-rich organelles present in epidermal granular cells. They fuse with the apical cell surface and discharge their contents into the intercellular space forming lamellar sheets. It was previously shown by electron microscopy that lamellar granules in biopsies of infants affected with harlequin ichthyosis are either absent or abnormal and no intercellular lamellae could be detected. A monoclonal antibody (AE17) directed against a protein component of lamellar granules was used for immunoblotting and immunohistochemical studies as an indication of both the presence and function of lamellar granules. Epidermal extracts from all harlequin and normal specimens tested showed an immunoreactive protein of 25-28 kD. Immunohistochemical staining of normal skin using AE17 showed apical cytoplasmic staining in the granular layer and intercellular staining between the granular and stratum corneum cells. Harlequin samples showed variable degrees of staining ranging from little to heavy apical cytoplasmic staining of granular cells. No intercellular staining was detected. The immunohistochemical staining pattern correlated with the electron microscopic localization of abnormal vesicles and the absence of intercellular lamellae in the affected samples. We conclude that the vesicles represent lamellar granules that contain the AE17 antigen but are structurally abnormal and defective in their ability to discharge both their lipid and protein contents into the intercellular space. We suggest that this defect in the lamellar granules represents the underlying basis for stratum corneum cell retention and subsequent accumulation of scale in harlequin ichthyosis.", "contents": "Abnormal lamellar granules in harlequin ichthyosis. Lamellar granules are specialized lipid-rich organelles present in epidermal granular cells. They fuse with the apical cell surface and discharge their contents into the intercellular space forming lamellar sheets. It was previously shown by electron microscopy that lamellar granules in biopsies of infants affected with harlequin ichthyosis are either absent or abnormal and no intercellular lamellae could be detected. A monoclonal antibody (AE17) directed against a protein component of lamellar granules was used for immunoblotting and immunohistochemical studies as an indication of both the presence and function of lamellar granules. Epidermal extracts from all harlequin and normal specimens tested showed an immunoreactive protein of 25-28 kD. Immunohistochemical staining of normal skin using AE17 showed apical cytoplasmic staining in the granular layer and intercellular staining between the granular and stratum corneum cells. Harlequin samples showed variable degrees of staining ranging from little to heavy apical cytoplasmic staining of granular cells. No intercellular staining was detected. The immunohistochemical staining pattern correlated with the electron microscopic localization of abnormal vesicles and the absence of intercellular lamellae in the affected samples. We conclude that the vesicles represent lamellar granules that contain the AE17 antigen but are structurally abnormal and defective in their ability to discharge both their lipid and protein contents into the intercellular space. We suggest that this defect in the lamellar granules represents the underlying basis for stratum corneum cell retention and subsequent accumulation of scale in harlequin ichthyosis."} {"id": "PMID:1281867", "title": "Identification of the retinoic acid and thyroid hormone receptor-responsive element in the human K14 keratin gene.", "content": "The promoter of human K14 keratin gene, specific for the basal layer of stratified epithelia, is regulated by nuclear receptors for retinoic acid and thyroid hormone. However, the DNA sequences responsible for this regulation have not yet been identified. To identify the retinoic acid-responsive site, we have devised a simple site-specific mutagenesis method and introduced mutations into the K14 keratin gene promoter. These mutations identify the retinoic acid-responsive site. The site consists of a cluster of consensus palindrome half-sites in various orientations. As shown previously, retinoic acid and thyroid hormone receptors can recognize and bind common sequences in regulated genes. Here, we describe mutations that abolish regulation by both receptors. Interestingly, the hormone-dependent and -independent regulatory sites of the thyroid hormone nuclear receptor can be separated. Clusters of half-sites that share structural organization with the K14 regulatory site were found in the K5 and K10 keratin gene promoters. Similar clusters may be responsible for retinoic acid-mediated transcription regulation in epidermis.", "contents": "Identification of the retinoic acid and thyroid hormone receptor-responsive element in the human K14 keratin gene. The promoter of human K14 keratin gene, specific for the basal layer of stratified epithelia, is regulated by nuclear receptors for retinoic acid and thyroid hormone. However, the DNA sequences responsible for this regulation have not yet been identified. To identify the retinoic acid-responsive site, we have devised a simple site-specific mutagenesis method and introduced mutations into the K14 keratin gene promoter. These mutations identify the retinoic acid-responsive site. The site consists of a cluster of consensus palindrome half-sites in various orientations. As shown previously, retinoic acid and thyroid hormone receptors can recognize and bind common sequences in regulated genes. Here, we describe mutations that abolish regulation by both receptors. Interestingly, the hormone-dependent and -independent regulatory sites of the thyroid hormone nuclear receptor can be separated. Clusters of half-sites that share structural organization with the K14 regulatory site were found in the K5 and K10 keratin gene promoters. Similar clusters may be responsible for retinoic acid-mediated transcription regulation in epidermis."} {"id": "PMID:1281868", "title": "The core protein of epican, a heparan sulfate proteoglycan on keratinocytes, is an alternative form of CD44.", "content": "Epican, a heparan sulfate proteoglycan, was recently identified on the surface of keratinocytes with the aid of a monoclonal antibody to its core protein. Using that antibody to screen a human keratinocyte cDNA library, a clone encoding the entire epican core protein was selected and sequenced. The core protein of epican is a form of CD44. The deduced protein sequence of 699 amino acids has a novel 339 amino acid domain inserted into the proximal extracellular domain of the standard, leukocyte form of CD44. The additional domain adds a number of potential N- and O-linked glycosylation sites and two proteolysis sites to this form of CD44.", "contents": "The core protein of epican, a heparan sulfate proteoglycan on keratinocytes, is an alternative form of CD44. Epican, a heparan sulfate proteoglycan, was recently identified on the surface of keratinocytes with the aid of a monoclonal antibody to its core protein. Using that antibody to screen a human keratinocyte cDNA library, a clone encoding the entire epican core protein was selected and sequenced. The core protein of epican is a form of CD44. The deduced protein sequence of 699 amino acids has a novel 339 amino acid domain inserted into the proximal extracellular domain of the standard, leukocyte form of CD44. The additional domain adds a number of potential N- and O-linked glycosylation sites and two proteolysis sites to this form of CD44."} {"id": "PMID:1281869", "title": "Carbohydrate determinant NeuAc-Gal beta (1-4) of N-linked glycans modulates the antigenic activity of human immunodeficiency virus type 1 glycoprotein gp120.", "content": "In the present study we investigated to what extent the peripheral carbohydrate structure of N-linked glycans influences the antigenic properties of human immunodeficiency virus type 1 glycoprotein 120 (gp120). Recombinant gp120 was purified from GMK cells infected with a recombinant vaccinia virus expressing gp120. Purified gp120 was then coated onto 96-well ELISA microplates and subjected to sequential removal of peripheral monosaccharide units. Modified or unmodified gp120 was then incubated with monoclonal antibodies recognizing specific epitopes of gp120 and with a reporter lectin to determine the extent of carbohydrate elimination. Antibody and lectin binding was quantified in an enzyme-linked system. We found that the carbohydrate structure NeuAc-Gal beta (1-4) of N-linked glycans, defined both by lectin reactivity and by specific glycosidases, is involved in modulating the binding of antibody to a number of epitopes of peptide nature. The binding of antibody to one class of epitopes, situated in a region between amino acids 200 and 230, was strongly increased by removal of NeuAc-Gal beta (1-4), whereas the binding to epitopes in the V3 region was decreased and the binding to epitopes in the far N-terminal region was not altered by the treatment. These results suggested that peripheral structures of N-glycans are involved in modulating the overall conformation of gp120.", "contents": "Carbohydrate determinant NeuAc-Gal beta (1-4) of N-linked glycans modulates the antigenic activity of human immunodeficiency virus type 1 glycoprotein gp120. In the present study we investigated to what extent the peripheral carbohydrate structure of N-linked glycans influences the antigenic properties of human immunodeficiency virus type 1 glycoprotein 120 (gp120). Recombinant gp120 was purified from GMK cells infected with a recombinant vaccinia virus expressing gp120. Purified gp120 was then coated onto 96-well ELISA microplates and subjected to sequential removal of peripheral monosaccharide units. Modified or unmodified gp120 was then incubated with monoclonal antibodies recognizing specific epitopes of gp120 and with a reporter lectin to determine the extent of carbohydrate elimination. Antibody and lectin binding was quantified in an enzyme-linked system. We found that the carbohydrate structure NeuAc-Gal beta (1-4) of N-linked glycans, defined both by lectin reactivity and by specific glycosidases, is involved in modulating the binding of antibody to a number of epitopes of peptide nature. The binding of antibody to one class of epitopes, situated in a region between amino acids 200 and 230, was strongly increased by removal of NeuAc-Gal beta (1-4), whereas the binding to epitopes in the V3 region was decreased and the binding to epitopes in the far N-terminal region was not altered by the treatment. These results suggested that peripheral structures of N-glycans are involved in modulating the overall conformation of gp120."} {"id": "PMID:1281870", "title": "Bovine coronavirus spike glycoprotein: localization of an immunodominant region at the amino-terminal end of S2.", "content": "We have identified the binding site of monoclonal antibodies (MAbs) against the S2 subunit of the bovine coronavirus spike (S) glycoprotein. The location of this site was first investigated by using prokaryotic expression of DNA restriction fragments covering the entire S gene. The amino acid sequence containing the antibody binding site was shortened from 70 to 20 amino acids by digestion of plasmid DNA with exonuclease III, followed by sequencing of the smallest digestion product encoding an immunoreactive fusion protein. Finally we synthesized a set of nonapeptides covering the 20 amino acid sequence extending from the N-terminal residue of the S2 subunit (Ala 769 to Tyr 798). MAbs reacted mainly with six consecutive overlapping peptides with the sequence TTGYRFTNFEPFTV. Polyclonal antibodies from hyperimmunized or convalescent animals reacted only with the recombinant proteins identified by MAbs, and the hyperimmune serum bound to the same set of peptides. This suggests that this highly conserved linear antigenic determinant corresponds to an immunodominant region. This region resembles both in location and immunodominance the linear determinant defined on the infectious bronchitis virus S2 subunit. The presence of similar regions in the N-terminal region of the S2 subunit of other coronaviruses is discussed.", "contents": "Bovine coronavirus spike glycoprotein: localization of an immunodominant region at the amino-terminal end of S2. We have identified the binding site of monoclonal antibodies (MAbs) against the S2 subunit of the bovine coronavirus spike (S) glycoprotein. The location of this site was first investigated by using prokaryotic expression of DNA restriction fragments covering the entire S gene. The amino acid sequence containing the antibody binding site was shortened from 70 to 20 amino acids by digestion of plasmid DNA with exonuclease III, followed by sequencing of the smallest digestion product encoding an immunoreactive fusion protein. Finally we synthesized a set of nonapeptides covering the 20 amino acid sequence extending from the N-terminal residue of the S2 subunit (Ala 769 to Tyr 798). MAbs reacted mainly with six consecutive overlapping peptides with the sequence TTGYRFTNFEPFTV. Polyclonal antibodies from hyperimmunized or convalescent animals reacted only with the recombinant proteins identified by MAbs, and the hyperimmune serum bound to the same set of peptides. This suggests that this highly conserved linear antigenic determinant corresponds to an immunodominant region. This region resembles both in location and immunodominance the linear determinant defined on the infectious bronchitis virus S2 subunit. The presence of similar regions in the N-terminal region of the S2 subunit of other coronaviruses is discussed."} {"id": "PMID:1281871", "title": "Increased systemic B- and T-lymphocyte responses in hereditary motor and sensory neuropathy (HMSN I).", "content": "Immune mechanisms of possible importance for the development and maintenance of peripheral nerve myelin breakdown in HMSN I were analysed by measuring B- and T-cell activation in blood, bone marrow and cerebrospinal fluid. Patients with polyneuropathies of other etiologies served as one control group and patients with tension headache as another. Flow cytometry of blood and bone marrow mononuclear cells revealed that an increased number of CD3+, CD4+ and CD4- CD8- T-cells expressed a late stage activation marker (Ta1). Analysis of T-cells primed for myelin antigens, by studies of IFN-gamma secretion in response to antigen in vitro, showed that both HMSN I and other polyneuropathy patients had low (but significant) numbers of T-cells recognizing whole PNS-myelin. Increased numbers of IgG- and IgM-producing cells were found in blood and bone marrow in the HMSN I patients. Patients with both HMSN I and the other polyneuropathies had few cells in peripheral blood and in bone marrow producing antibodies binding to P2, MAG and MBP in a solid phase immunospot assay. Many cells in the cerebrospinal fluid produced antibodies against MAG. Thus, there was a strong general activation of B- and T-cells in HMSN I while the immunity directed toward peripheral nerve was only slightly elevated. It is an open question if this immune activation is related to the primary gene defect or a secondary event to the nerve damage. The pathogenetic importance of the immune response in maintaining the nerve damage in HMSN I is unclear.", "contents": "Increased systemic B- and T-lymphocyte responses in hereditary motor and sensory neuropathy (HMSN I). Immune mechanisms of possible importance for the development and maintenance of peripheral nerve myelin breakdown in HMSN I were analysed by measuring B- and T-cell activation in blood, bone marrow and cerebrospinal fluid. Patients with polyneuropathies of other etiologies served as one control group and patients with tension headache as another. Flow cytometry of blood and bone marrow mononuclear cells revealed that an increased number of CD3+, CD4+ and CD4- CD8- T-cells expressed a late stage activation marker (Ta1). Analysis of T-cells primed for myelin antigens, by studies of IFN-gamma secretion in response to antigen in vitro, showed that both HMSN I and other polyneuropathy patients had low (but significant) numbers of T-cells recognizing whole PNS-myelin. Increased numbers of IgG- and IgM-producing cells were found in blood and bone marrow in the HMSN I patients. Patients with both HMSN I and the other polyneuropathies had few cells in peripheral blood and in bone marrow producing antibodies binding to P2, MAG and MBP in a solid phase immunospot assay. Many cells in the cerebrospinal fluid produced antibodies against MAG. Thus, there was a strong general activation of B- and T-cells in HMSN I while the immunity directed toward peripheral nerve was only slightly elevated. It is an open question if this immune activation is related to the primary gene defect or a secondary event to the nerve damage. The pathogenetic importance of the immune response in maintaining the nerve damage in HMSN I is unclear."} {"id": "PMID:1281872", "title": "Thrombospondin, a platelet alpha-granule and matrix glycoprotein, is increased in muscle basement membrane of patients with amyotrophic lateral sclerosis.", "content": "In an attempt to obtain a biological marker for the enigmatic and fatal neurologic disorder, amyotrophic lateral sclerosis (ALS), several laboratories have explored alterations in various extracellular matrix components in both skeletal muscle and skin. We have studied the distribution of fibronectin, laminin, heparan sulfate proteoglycan (HSPG) and collagen types I, III and IV, along with the platelet alpha-granule glycoprotein, thrombospondin (TSP), by immunofluorescence in frozen sections of muscle from control denervating conditions and ALS patients. In ALS and control muscle, types I and III collagen were localized to the endomysium and the perimysium. Type IV collagen and laminin precisely delineated each muscle fiber (endomysium or basement membrane) but did not stain the perimysium. We found no marked quantitative or qualitative differences in the distribution of collagen types I, III and IV, laminin, fibronectin or HSPG in ALS patients compared to controls. However, when polyclonal antisera for TSP was used we found a marked increase in the deposition of this multi-domain glycoprotein in ALS patients' muscle compared to control muscle. Quantitative analysis of soluble extracts from control and ALS patients' muscle by ELISA also indicated that TSP was increased in ALS. TSP is released from platelet alpha-granules in response to thrombin stimulation. TSP elevation implies coagulation activity via the extravascular thrombolytic system in ALS and may correlate with regeneration. Other studies have indicated decreased circulating protease inhibitors and increased serine proteases in this disorder.", "contents": "Thrombospondin, a platelet alpha-granule and matrix glycoprotein, is increased in muscle basement membrane of patients with amyotrophic lateral sclerosis. In an attempt to obtain a biological marker for the enigmatic and fatal neurologic disorder, amyotrophic lateral sclerosis (ALS), several laboratories have explored alterations in various extracellular matrix components in both skeletal muscle and skin. We have studied the distribution of fibronectin, laminin, heparan sulfate proteoglycan (HSPG) and collagen types I, III and IV, along with the platelet alpha-granule glycoprotein, thrombospondin (TSP), by immunofluorescence in frozen sections of muscle from control denervating conditions and ALS patients. In ALS and control muscle, types I and III collagen were localized to the endomysium and the perimysium. Type IV collagen and laminin precisely delineated each muscle fiber (endomysium or basement membrane) but did not stain the perimysium. We found no marked quantitative or qualitative differences in the distribution of collagen types I, III and IV, laminin, fibronectin or HSPG in ALS patients compared to controls. However, when polyclonal antisera for TSP was used we found a marked increase in the deposition of this multi-domain glycoprotein in ALS patients' muscle compared to control muscle. Quantitative analysis of soluble extracts from control and ALS patients' muscle by ELISA also indicated that TSP was increased in ALS. TSP is released from platelet alpha-granules in response to thrombin stimulation. TSP elevation implies coagulation activity via the extravascular thrombolytic system in ALS and may correlate with regeneration. Other studies have indicated decreased circulating protease inhibitors and increased serine proteases in this disorder."} {"id": "PMID:1281873", "title": "Immunocytochemical staining with antibodies against protein kinase C and its isozymes in the turtle retina.", "content": "An LM immunocytochemical study has investigated the patterns of staining in turtle retina with monoclonal antibodies to the alpha, beta and gamma isozymes of protein kinase C. The protein kinase C-gamma antibody reveals cells in the ganglion cell layer, occasional amacrine cells and faint banding in strata 2 and 4 of the inner plexiform layer. The protein kinase C-beta antibody stains primarily amacrine cells that have dendrites running in strata 2, in 4 close to the 3/4 border and on the 4/5 border of the inner plexiform layer. Protein kinase C-alpha immunoreactivity is seen in a population of bipolar cells. The latter are characterized by stained axon terminals in strata 3 and 4 of the inner plexiform layer. A type of amacrine cell, different from those seen with the other antibodies, is also immunoreactive to protein kinase C-alpha. EM immunocytochemistry (using a polyclonal antibody) reveals protein kinase C immunoreactivity in photoreceptor cells, bipolar cells, amacrine cells and ganglion cells. In photoreceptors protein kinase C immunoreactivity occurs as patchy staining associated with vesicles and the plasmalemma in pedicles and telodendria. Some varieties of bipolar cell display protein kinase C reaction product throughout the entire cell. Their dendrites contact photoreceptor pedicles at wide-cleft basal junctions and ribbon and non-ribbon related narrow cleft junctions. A few lateral elements per cone or rod pedicle are always protein kinase C-immunoreactive. Amacrine and ganglion cells typically show small clumps of protein kinase C immunoreactivity around vesicles and close to the postsynaptic membranes. Synaptic boutons of some varieties of amacrine cell stain more uniformly. Protein kinase C-immunoreactive bipolar cells are most commonly presynaptic in stratum 4 of the inner plexiform layer, while protein kinase C-immunoreactive amacrine cells are both pre- and postsynaptic throughout strata 1, 2, 3 and 4. Stratum 5 appears to be almost devoid of protein kinase C-immunoreactive neural profiles.", "contents": "Immunocytochemical staining with antibodies against protein kinase C and its isozymes in the turtle retina. An LM immunocytochemical study has investigated the patterns of staining in turtle retina with monoclonal antibodies to the alpha, beta and gamma isozymes of protein kinase C. The protein kinase C-gamma antibody reveals cells in the ganglion cell layer, occasional amacrine cells and faint banding in strata 2 and 4 of the inner plexiform layer. The protein kinase C-beta antibody stains primarily amacrine cells that have dendrites running in strata 2, in 4 close to the 3/4 border and on the 4/5 border of the inner plexiform layer. Protein kinase C-alpha immunoreactivity is seen in a population of bipolar cells. The latter are characterized by stained axon terminals in strata 3 and 4 of the inner plexiform layer. A type of amacrine cell, different from those seen with the other antibodies, is also immunoreactive to protein kinase C-alpha. EM immunocytochemistry (using a polyclonal antibody) reveals protein kinase C immunoreactivity in photoreceptor cells, bipolar cells, amacrine cells and ganglion cells. In photoreceptors protein kinase C immunoreactivity occurs as patchy staining associated with vesicles and the plasmalemma in pedicles and telodendria. Some varieties of bipolar cell display protein kinase C reaction product throughout the entire cell. Their dendrites contact photoreceptor pedicles at wide-cleft basal junctions and ribbon and non-ribbon related narrow cleft junctions. A few lateral elements per cone or rod pedicle are always protein kinase C-immunoreactive. Amacrine and ganglion cells typically show small clumps of protein kinase C immunoreactivity around vesicles and close to the postsynaptic membranes. Synaptic boutons of some varieties of amacrine cell stain more uniformly. Protein kinase C-immunoreactive bipolar cells are most commonly presynaptic in stratum 4 of the inner plexiform layer, while protein kinase C-immunoreactive amacrine cells are both pre- and postsynaptic throughout strata 1, 2, 3 and 4. Stratum 5 appears to be almost devoid of protein kinase C-immunoreactive neural profiles."} {"id": "PMID:1281874", "title": "Tumour angiogenesis in prostatic carcinoma with and without bone marrow metastasis: a morphometric study.", "content": "One hundred and one cases of clinical prostatic carcinoma (PCa), primary site, were analysed to define the interrelationship between tumour angiogenesis, histological grade, and bone marrow metastasis. Tumour angiogenesis was determined by the blood capillary density ratio (BCDR; a/b), defined as the ratio between the area of the blood capillaries (a) and the area of the tumour (b). The BCDR was evaluated by a colour image analysis system employing a computerized morphometrical method. A total of 43 cases of PCa with bone marrow metastasis (stage D2) and 58 cases of PCa without metastasis (stage B, C) were utilized. The prostatic carcinomas were classified into three groups (low, intermediate, and high) using Gleason's grading system. The BCDR of the primary PCa with bone marrow metastasis was similar in each of the three histologically graded scores. On the other hand, in the cases of PCa without metastasis, the BCDR of high score PCa was higher than those of the low and intermediate score PCa (U-test; P < 0.001). The BCDR of the high score PCa without metastasis was similar to that of the PCa with bone marrow metastasis. The BCDR may provide help in predicting tumour progression with regard to bone marrow metastasis of PCa with low and intermediate Gleason's scores.", "contents": "Tumour angiogenesis in prostatic carcinoma with and without bone marrow metastasis: a morphometric study. One hundred and one cases of clinical prostatic carcinoma (PCa), primary site, were analysed to define the interrelationship between tumour angiogenesis, histological grade, and bone marrow metastasis. Tumour angiogenesis was determined by the blood capillary density ratio (BCDR; a/b), defined as the ratio between the area of the blood capillaries (a) and the area of the tumour (b). The BCDR was evaluated by a colour image analysis system employing a computerized morphometrical method. A total of 43 cases of PCa with bone marrow metastasis (stage D2) and 58 cases of PCa without metastasis (stage B, C) were utilized. The prostatic carcinomas were classified into three groups (low, intermediate, and high) using Gleason's grading system. The BCDR of the primary PCa with bone marrow metastasis was similar in each of the three histologically graded scores. On the other hand, in the cases of PCa without metastasis, the BCDR of high score PCa was higher than those of the low and intermediate score PCa (U-test; P < 0.001). The BCDR of the high score PCa without metastasis was similar to that of the PCa with bone marrow metastasis. The BCDR may provide help in predicting tumour progression with regard to bone marrow metastasis of PCa with low and intermediate Gleason's scores."} {"id": "PMID:1281876", "title": "Cardiac function in rats with acute renal failure.", "content": "Inotropic responses of isolated cardiac preparations from rats with glycerol-induced acute renal failure (ARF) were recorded, following a range of cardiac stimulants. Left atria of rats with ARF showed diminished inotropic responses only to the calcium agonist Bay K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5 -carboxylate) whilst right ventricular strips exhibited reduced responses to isoprenaline, 3-isobutyl-1-methylxanthine, Ca2+ and Bay K 8644. Investigations of cardiac mitochondrial respiration indicated that there is a site-unspecific 'pseudo' uncoupling of oxidative phosphorylation in ARF but that electron transport is unaffected. This uncoupling of oxidative phosphorylation did not have any detectable effect on either levels of total adenine nucleotides and creatine phosphate or cellular energy charge. Measurements were also made of the activity of pyruvate dehydrogenase which provides an index of mitochondrial Ca2+ levels. The proportion of pyruvate dehydrogenase in its active form was threefold higher following isoprenaline injection in hearts of rats with ARF compared with controls. The results suggest that in hearts of rats with ARF there is a change in the number, affinity, efficacy or coupling of the dihydropyridine receptor on the L-type calcium channel. Moreover, in the ventricle, a defect in cellular Ca2+ control, resulting in an increase in mitochondrial Ca2+ uptake, may contribute to the depression of inotropic response to the range of cardiac stimulants tested.", "contents": "Cardiac function in rats with acute renal failure. Inotropic responses of isolated cardiac preparations from rats with glycerol-induced acute renal failure (ARF) were recorded, following a range of cardiac stimulants. Left atria of rats with ARF showed diminished inotropic responses only to the calcium agonist Bay K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-5 -carboxylate) whilst right ventricular strips exhibited reduced responses to isoprenaline, 3-isobutyl-1-methylxanthine, Ca2+ and Bay K 8644. Investigations of cardiac mitochondrial respiration indicated that there is a site-unspecific 'pseudo' uncoupling of oxidative phosphorylation in ARF but that electron transport is unaffected. This uncoupling of oxidative phosphorylation did not have any detectable effect on either levels of total adenine nucleotides and creatine phosphate or cellular energy charge. Measurements were also made of the activity of pyruvate dehydrogenase which provides an index of mitochondrial Ca2+ levels. The proportion of pyruvate dehydrogenase in its active form was threefold higher following isoprenaline injection in hearts of rats with ARF compared with controls. The results suggest that in hearts of rats with ARF there is a change in the number, affinity, efficacy or coupling of the dihydropyridine receptor on the L-type calcium channel. Moreover, in the ventricle, a defect in cellular Ca2+ control, resulting in an increase in mitochondrial Ca2+ uptake, may contribute to the depression of inotropic response to the range of cardiac stimulants tested."} {"id": "PMID:1281877", "title": "Analysis of the interaction between lacidipine and BAY K 8644 in two isolated rabbit arteries.", "content": "The calcium antagonist activity of the long-acting 1,4-dihydropyridine (DHP) lacidipine has been analyzed in rabbit ear artery (REA) and rabbit basilar artery (RBA). Its potency has been estimated from its interaction with BAY K 8644 using a three state gating model of the voltage-operated calcium channel. As a contractile agent, BAY K 8644 exhibited a bell-shaped concentration-response curve in both arteries. For fitting purposes, a second binding interaction between BAY K 8644 and the channel has been used to describe the descending part of the curve. The K(app)s for lacidipine and three other DHPs (nifedipine, nitrendipine and amlodipine) have been compared to pA2 values obtained from displacement of calcium concentration-response curves. In both REA and RBA the K(app)s for the four DHPs were not significantly different compared to their pA2s. The pK(app) values for lacidipine were estimated as 9.80 for REA and 10.20 for RBA.", "contents": "Analysis of the interaction between lacidipine and BAY K 8644 in two isolated rabbit arteries. The calcium antagonist activity of the long-acting 1,4-dihydropyridine (DHP) lacidipine has been analyzed in rabbit ear artery (REA) and rabbit basilar artery (RBA). Its potency has been estimated from its interaction with BAY K 8644 using a three state gating model of the voltage-operated calcium channel. As a contractile agent, BAY K 8644 exhibited a bell-shaped concentration-response curve in both arteries. For fitting purposes, a second binding interaction between BAY K 8644 and the channel has been used to describe the descending part of the curve. The K(app)s for lacidipine and three other DHPs (nifedipine, nitrendipine and amlodipine) have been compared to pA2 values obtained from displacement of calcium concentration-response curves. In both REA and RBA the K(app)s for the four DHPs were not significantly different compared to their pA2s. The pK(app) values for lacidipine were estimated as 9.80 for REA and 10.20 for RBA."} {"id": "PMID:1281878", "title": "SL 84.0418: a novel, potent and selective alpha-2 adrenoceptor antagonist: in vitro pharmacological profile.", "content": "One novel, potent and selective alpha-2 adrenoceptor antagonist is 2-(4,5-dihydro-1H-imidazol-2-yl)-1,2,4,5-tetrahydro-2- propylpyrrolo[3,2,1-hi]-indole hydrochloride (SL 84.0418). It inhibits with high affinity the radioligand binding to rat cortical alpha-2 adrenoceptors, as well as to human platelet alpha-2 adrenoceptors labeled with [3H]idazoxan (Ki = 7 nM). SL 84.0418 has low affinity for alpha-1 adrenoceptors labeled with [3H]prazosin (Ki = 3.3 microM). In vitro, SL 84.0418 has no alpha agonist properties, whereas it is a potent alpha-2 adrenoceptor antagonist at both pre- and postsynaptic alpha-2 adrenoceptors. In contrast, it possesses low potency as an antagonist at postsynaptic alpha-1 adrenoceptors demonstrating a more than 1000-fold selectivity toward alpha-2 compared with alpha-1 adrenoceptors. In the same tests, the alpha-2 adrenoceptor antagonist idazoxan had a selectivity ratio of 200. SL 84.0418 is the racemic mixture of two enantiomers, SL 86.0715 [(+) enantiomer] and SL 86.0714 [(-) enantiomer]. The alpha-2 adrenoceptor blocking activities reside with SL 86.0715. Similar to idazoxan, SL 84.0418 increases in a concentration-dependent manner the electrically evoked release of [3H]norepinephrine from rat hypothalamic slices through the blockade of the presynaptic inhibitory alpha-2 adrenoceptors. In isolated hamster adipocytes, SL 84.0418 potently antagonizes the inhibition of lipolysis induced by UK 14,304. In addition, SL 84.0418 inhibits epinephrine-induced aggregation of rabbit platelets, effects mediated by postsynaptic alpha-2 adrenoceptors. SL 84.0418 does not inhibit (IC50 > 1,000 nM) radioligand binding to other receptors or recognition sites, nor does it inhibit calcium, sodium or potassium channels.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "SL 84.0418: a novel, potent and selective alpha-2 adrenoceptor antagonist: in vitro pharmacological profile. One novel, potent and selective alpha-2 adrenoceptor antagonist is 2-(4,5-dihydro-1H-imidazol-2-yl)-1,2,4,5-tetrahydro-2- propylpyrrolo[3,2,1-hi]-indole hydrochloride (SL 84.0418). It inhibits with high affinity the radioligand binding to rat cortical alpha-2 adrenoceptors, as well as to human platelet alpha-2 adrenoceptors labeled with [3H]idazoxan (Ki = 7 nM). SL 84.0418 has low affinity for alpha-1 adrenoceptors labeled with [3H]prazosin (Ki = 3.3 microM). In vitro, SL 84.0418 has no alpha agonist properties, whereas it is a potent alpha-2 adrenoceptor antagonist at both pre- and postsynaptic alpha-2 adrenoceptors. In contrast, it possesses low potency as an antagonist at postsynaptic alpha-1 adrenoceptors demonstrating a more than 1000-fold selectivity toward alpha-2 compared with alpha-1 adrenoceptors. In the same tests, the alpha-2 adrenoceptor antagonist idazoxan had a selectivity ratio of 200. SL 84.0418 is the racemic mixture of two enantiomers, SL 86.0715 [(+) enantiomer] and SL 86.0714 [(-) enantiomer]. The alpha-2 adrenoceptor blocking activities reside with SL 86.0715. Similar to idazoxan, SL 84.0418 increases in a concentration-dependent manner the electrically evoked release of [3H]norepinephrine from rat hypothalamic slices through the blockade of the presynaptic inhibitory alpha-2 adrenoceptors. In isolated hamster adipocytes, SL 84.0418 potently antagonizes the inhibition of lipolysis induced by UK 14,304. In addition, SL 84.0418 inhibits epinephrine-induced aggregation of rabbit platelets, effects mediated by postsynaptic alpha-2 adrenoceptors. SL 84.0418 does not inhibit (IC50 > 1,000 nM) radioligand binding to other receptors or recognition sites, nor does it inhibit calcium, sodium or potassium channels.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281879", "title": "Modulation of neutrophil superoxide generation by inhibitors of protein kinase C, calmodulin, diacylglycerol and myosin light chain kinases, and peptidyl prolyl cis-trans isomerase.", "content": "To assess the role of protein kinase C (PKC) in the respiratory burst of adherent human polymorphonuclear leukocytes (PMNL), reduction of ferricytochrome C by cells triggered with a phorbol ester (PMA), ionophore A23187, serum-treated zymosan (STZ) or three lipid derivatives, 3-decanoyl-sn-glycerol (G-3-OCOC9), (R,R)-1,4-diethyl-2-O-decyl-L-tartrate (Tt-2-OC10) and 3-decyloxy-5-hydroxymethylphenol (DHP) was examined in a microtiter plate procedure in the presence of inhibitors of PKC and, for comparison, inhibitors of calmodulin, diacylglycerol and myosin light chain kinases and the peptidyl-prolyl cis-trans isomerase activity of fujiphilin. 1) Of the protein kinase inhibitors examined, Ro 31-7549 and staurosporine reduced responses to all stimuli except possibly STZ; in contrast, K252a and the myosin light chain kinase inhibitors ML-7 and ML-9 blocked responses to A23187 and STZ better than those triggered by PMA. H-7 reduced responses to A23187, DHP and G-3-OCOC9, and calphostin, palmitoyl carnitine, sphingosine and the multifunctional drugs TMB-8 and W-7 reduced A23187; they also, when examined, reduced decane derivative-induced O2- production more effectively than PMA- and STZ-triggered responses. Polymyxin B, 4 alpha-PMA and retinal displayed no inhibitory capacity. 2) Of the selective calmodulin antagonists, CGS 9343B, Ro 22-4839 and calmidazolium did not inhibit the oxidative response irrespective of the stimulus used, whereas metofenazate reduced those evoked by A23187, DHP, G-3-OCOC9 and STZ.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Modulation of neutrophil superoxide generation by inhibitors of protein kinase C, calmodulin, diacylglycerol and myosin light chain kinases, and peptidyl prolyl cis-trans isomerase. To assess the role of protein kinase C (PKC) in the respiratory burst of adherent human polymorphonuclear leukocytes (PMNL), reduction of ferricytochrome C by cells triggered with a phorbol ester (PMA), ionophore A23187, serum-treated zymosan (STZ) or three lipid derivatives, 3-decanoyl-sn-glycerol (G-3-OCOC9), (R,R)-1,4-diethyl-2-O-decyl-L-tartrate (Tt-2-OC10) and 3-decyloxy-5-hydroxymethylphenol (DHP) was examined in a microtiter plate procedure in the presence of inhibitors of PKC and, for comparison, inhibitors of calmodulin, diacylglycerol and myosin light chain kinases and the peptidyl-prolyl cis-trans isomerase activity of fujiphilin. 1) Of the protein kinase inhibitors examined, Ro 31-7549 and staurosporine reduced responses to all stimuli except possibly STZ; in contrast, K252a and the myosin light chain kinase inhibitors ML-7 and ML-9 blocked responses to A23187 and STZ better than those triggered by PMA. H-7 reduced responses to A23187, DHP and G-3-OCOC9, and calphostin, palmitoyl carnitine, sphingosine and the multifunctional drugs TMB-8 and W-7 reduced A23187; they also, when examined, reduced decane derivative-induced O2- production more effectively than PMA- and STZ-triggered responses. Polymyxin B, 4 alpha-PMA and retinal displayed no inhibitory capacity. 2) Of the selective calmodulin antagonists, CGS 9343B, Ro 22-4839 and calmidazolium did not inhibit the oxidative response irrespective of the stimulus used, whereas metofenazate reduced those evoked by A23187, DHP, G-3-OCOC9 and STZ.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281880", "title": "Heparin, dextran and trypan blue allosterically modulate M2 muscarinic receptor binding properties and interfere with receptor-mediated inhibition of adenylate cyclase.", "content": "The influences of heparin, dextran and trypan blue on muscarinic receptor binding properties and inhibition of adenylate cyclase were investigated in homogenates of the rat heart. These compounds caused a concentration-dependent enhancement in the specific binding of the muscarinic antagonist [3H]N-methylscopolamine ([3H]NMS) when measured at a radioligand concentration of approximately 0.5 nM in magnesium-containing, low ionic strength buffer. The maximal enhancements of [3H]NMS binding were 2.89-, 1.68- and 1.43-fold increases for heparin, dextran and trypan blue, respectively; the EC50 values for this effect were 0.12, 0.033 and 4.6 microM, respectively. The effects of heparin, dextran and trypan blue on [3H]NMS binding were attributed mainly to an increase in the overall affinity of muscarinic receptors for [3H]NMS, and were greatly attenuated by 100 mM NaCl. These effects were qualitatively similar to those produced by GTP. Heparin, dextran and trypan blue also affected the binding of the muscarinic agonist oxotremorine-M in a manner similar to that of GTP; that is, in the presence of these compounds, agonist affinity was decreased. Our experiments also showed that heparin and dextran attenuate the inhibition of adenylate cyclase activity caused by oxotremorine-M in myocardial homogenates without influencing basal adenylate cyclase activity. We conclude that heparin and dextran interfere with the muscarinic receptor-G protein coupling in the rat heart.", "contents": "Heparin, dextran and trypan blue allosterically modulate M2 muscarinic receptor binding properties and interfere with receptor-mediated inhibition of adenylate cyclase. The influences of heparin, dextran and trypan blue on muscarinic receptor binding properties and inhibition of adenylate cyclase were investigated in homogenates of the rat heart. These compounds caused a concentration-dependent enhancement in the specific binding of the muscarinic antagonist [3H]N-methylscopolamine ([3H]NMS) when measured at a radioligand concentration of approximately 0.5 nM in magnesium-containing, low ionic strength buffer. The maximal enhancements of [3H]NMS binding were 2.89-, 1.68- and 1.43-fold increases for heparin, dextran and trypan blue, respectively; the EC50 values for this effect were 0.12, 0.033 and 4.6 microM, respectively. The effects of heparin, dextran and trypan blue on [3H]NMS binding were attributed mainly to an increase in the overall affinity of muscarinic receptors for [3H]NMS, and were greatly attenuated by 100 mM NaCl. These effects were qualitatively similar to those produced by GTP. Heparin, dextran and trypan blue also affected the binding of the muscarinic agonist oxotremorine-M in a manner similar to that of GTP; that is, in the presence of these compounds, agonist affinity was decreased. Our experiments also showed that heparin and dextran attenuate the inhibition of adenylate cyclase activity caused by oxotremorine-M in myocardial homogenates without influencing basal adenylate cyclase activity. We conclude that heparin and dextran interfere with the muscarinic receptor-G protein coupling in the rat heart."} {"id": "PMID:1281881", "title": "Maitotoxin, a novel activator of mediator release from human basophils, induces large increases in cytosolic calcium resulting in histamine, but not leukotriene C4, release.", "content": "Maitotoxin (MTX) is a potent marine toxin which stimulates several Ca(++)-dependent processes presumably through an increase in Ca++ permeability. We have examined the effect of MTX on the release of chemical mediators from human basophils and its mechanism of action. MTX (1-20 ng/ml) induced histamine release (37-100%) from both mixed leukocyte preparations and purified basophils. Histamine release activated by MTX was slow (t 1/2 approximately equal to 15 min), temperature and Ca++ dependent (optimal at 37 degrees C and 1-2.5 mM Ca++). Sr++ ion could substitute for Ca++ in the secretory process. Digital video microscopy analysis of purified (> 70%) basophils revealed that MTX (1-20 ng/ml) induced a slow and marked increase of cytosolic Ca++ levels that was temporally coincident with histamine release. MTX (1-20 ng/ml) stimulated the release of sulfidopeptide leukotriene C4 from mixed leukocyte preparations (approximately equal to 0.5% basophils). However, purified basophils (77 +/- 7%) showed no sulfidopeptide leukotriene C4 release even in the presence of large histamine secretion (84 +/- 14%). Two organic Ca(++)-channel entry blockers, verapamil and diltiazem (1-30 microM) inhibited the release of histamine induced by MTX, whereas the dihydropyridine nifedipine (0.1-10 microM) caused only minimal inhibition. These results suggest that MTX represents a novel stimulus useful to study the role of Ca++ in human basophil mediator release.", "contents": "Maitotoxin, a novel activator of mediator release from human basophils, induces large increases in cytosolic calcium resulting in histamine, but not leukotriene C4, release. Maitotoxin (MTX) is a potent marine toxin which stimulates several Ca(++)-dependent processes presumably through an increase in Ca++ permeability. We have examined the effect of MTX on the release of chemical mediators from human basophils and its mechanism of action. MTX (1-20 ng/ml) induced histamine release (37-100%) from both mixed leukocyte preparations and purified basophils. Histamine release activated by MTX was slow (t 1/2 approximately equal to 15 min), temperature and Ca++ dependent (optimal at 37 degrees C and 1-2.5 mM Ca++). Sr++ ion could substitute for Ca++ in the secretory process. Digital video microscopy analysis of purified (> 70%) basophils revealed that MTX (1-20 ng/ml) induced a slow and marked increase of cytosolic Ca++ levels that was temporally coincident with histamine release. MTX (1-20 ng/ml) stimulated the release of sulfidopeptide leukotriene C4 from mixed leukocyte preparations (approximately equal to 0.5% basophils). However, purified basophils (77 +/- 7%) showed no sulfidopeptide leukotriene C4 release even in the presence of large histamine secretion (84 +/- 14%). Two organic Ca(++)-channel entry blockers, verapamil and diltiazem (1-30 microM) inhibited the release of histamine induced by MTX, whereas the dihydropyridine nifedipine (0.1-10 microM) caused only minimal inhibition. These results suggest that MTX represents a novel stimulus useful to study the role of Ca++ in human basophil mediator release."} {"id": "PMID:1281882", "title": "3'-C-branched 2'-deoxy-5-methyluridines: synthesis, enzyme inhibition, and antiviral properties.", "content": "A synthesis scheme for 3'-C-methyl-2'-deoxynucleosides and 3'-C-methylidene-2',3'-dideoxy-5-methyluridine has been proposed with 2-deoxyribose as the starting material. Methyl 5-O-benzoyl-2-deoxyribofuranose was oxidized and the mixture of the 3'-keto derivatives was separated into the alpha- and beta-anomers. The beta-keto derivative was converted by reaction with MeMgBr, and after reaction with thymine and subsequent deprotection 1-(3'-C-methyl-2'-alpha-deoxy-alpha-D-threo-pentofuranosyl)thymine and its beta-anomer were obtained. The same reactions with the alpha-keto sugar gave 1-(3'-C-methyl-2'-deoxy-alpha-D-erythro-pentofuranosyl)thymine and its beta-anomer. 1-(5-O-Benzoyl-3'-C-methyl-2'-deoxy-alpha-D-threo-pentofuranosyl)thymine was converted to a mixture of 3'-C-methylidene-2',3'-dideoxy-5-methyluridine and 3'-C-methyl-2',3'-dideoxy-2',3'-didehydro-5-methyluridine, which were separated. The stereoselectivity of the Grignard reagent's attachment to 2-deoxyfuranose 3-ulosides has been ruled by the substitute configuration at Cl. Also, the effect of the hydroxyl or OBz group configuration at C3 on the condensation stereoselectivity of 3-C-methyl-2-deoxyfuranosides with silylated thymine has been studied. The structure of the obtained compounds was proved by 1H NMR UV, 13C NMR, and CD spectroscopy, as well as elemental (C, H, N) analysis. The C2'-endo-C1'-exo conformation, the anti conformation of thymine in relation to the glycosidic bond, and the gauche+conformation in relation to the C4'-C5' bond are characteristic for the 3'-C-methyl-2'-deoxythymidine structure in the crystals. 3'-C-Methyl-2'-deoxythymidine 5'-triphosphate was synthesized and proved to be a competitive inhibitor, with respect to dTTP, of a number of DNA polymerases, including the reverse transcriptases of human immunodeficiency virus type 1 (HIV-1) and avian myeloblastosis virus (AMV). None of the DNA polymerases examined were able to incorporate this compound into the growing DNA chain. In contrast, 3'-C-methylidene-2',3'-dideoxy-5-methyluridine 5'-triphosphate was found to be incorporated at the 3'-end of the DNA chain by HIV-1 reverse transcriptase, albeit with very low efficiency. 3'-C-Methyl-2'-deoxy-5-methyluridine did not suppress HIV-1 replication in MT-4 cells at 500 microM while its 5'-phosphite derivative exhibited modest anti-HIV-1 activity.", "contents": "3'-C-branched 2'-deoxy-5-methyluridines: synthesis, enzyme inhibition, and antiviral properties. A synthesis scheme for 3'-C-methyl-2'-deoxynucleosides and 3'-C-methylidene-2',3'-dideoxy-5-methyluridine has been proposed with 2-deoxyribose as the starting material. Methyl 5-O-benzoyl-2-deoxyribofuranose was oxidized and the mixture of the 3'-keto derivatives was separated into the alpha- and beta-anomers. The beta-keto derivative was converted by reaction with MeMgBr, and after reaction with thymine and subsequent deprotection 1-(3'-C-methyl-2'-alpha-deoxy-alpha-D-threo-pentofuranosyl)thymine and its beta-anomer were obtained. The same reactions with the alpha-keto sugar gave 1-(3'-C-methyl-2'-deoxy-alpha-D-erythro-pentofuranosyl)thymine and its beta-anomer. 1-(5-O-Benzoyl-3'-C-methyl-2'-deoxy-alpha-D-threo-pentofuranosyl)thymine was converted to a mixture of 3'-C-methylidene-2',3'-dideoxy-5-methyluridine and 3'-C-methyl-2',3'-dideoxy-2',3'-didehydro-5-methyluridine, which were separated. The stereoselectivity of the Grignard reagent's attachment to 2-deoxyfuranose 3-ulosides has been ruled by the substitute configuration at Cl. Also, the effect of the hydroxyl or OBz group configuration at C3 on the condensation stereoselectivity of 3-C-methyl-2-deoxyfuranosides with silylated thymine has been studied. The structure of the obtained compounds was proved by 1H NMR UV, 13C NMR, and CD spectroscopy, as well as elemental (C, H, N) analysis. The C2'-endo-C1'-exo conformation, the anti conformation of thymine in relation to the glycosidic bond, and the gauche+conformation in relation to the C4'-C5' bond are characteristic for the 3'-C-methyl-2'-deoxythymidine structure in the crystals. 3'-C-Methyl-2'-deoxythymidine 5'-triphosphate was synthesized and proved to be a competitive inhibitor, with respect to dTTP, of a number of DNA polymerases, including the reverse transcriptases of human immunodeficiency virus type 1 (HIV-1) and avian myeloblastosis virus (AMV). None of the DNA polymerases examined were able to incorporate this compound into the growing DNA chain. In contrast, 3'-C-methylidene-2',3'-dideoxy-5-methyluridine 5'-triphosphate was found to be incorporated at the 3'-end of the DNA chain by HIV-1 reverse transcriptase, albeit with very low efficiency. 3'-C-Methyl-2'-deoxy-5-methyluridine did not suppress HIV-1 replication in MT-4 cells at 500 microM while its 5'-phosphite derivative exhibited modest anti-HIV-1 activity."} {"id": "PMID:1281883", "title": "Differences in Ca(2+)-mediation of hypotonic and Na(+)-nutrient regulatory volume decrease in suspensions of jejunal enterocytes.", "content": "We determined differences in the Ca2+ signalling of K+ and Cl- conductances required for Regulatory Volume Decrease (RVD) in jejunal villus enterocytes passively swollen (0.5 or 0.95.isotonic) compared with swelling because of the absorption of D-glucose (D-Glc) or L-Alanine (L-Ala). Cell volume was measured using electronic cell sizing. In nominally Ca(2+)-free medium containing EGTA (100 microM) RVD after 0.5 or 0.95.isotonic challenge was prevented. L-Ala swelling and subsequent RVD was influenced in Ca(2+)-free medium. Villus cells were incubated with 10 microM of the acetomethoxy derivative of 1,2.bis (2-aminophenoxy) ethane N,N,N1,N1 tetracetic acid (BAPTA-AM) and RVD after 0.5.isotonic swelling or L-Ala swelling was prevented. Niguldipine (0.1 microM), nifedipine (5 microM), diltiazem (100 microM), Ni2+, and Co2+ (1 mM) all prevented hypotonic RVD but had no effect on RVD after L-Ala addition. Charybdotoxin (25 nM) a potent inhibitor of Ca(2+)-activated K+ channels, had no effect on hypotonic RVD but prevented RVD of villus cells swollen by D-Glc. We used the calmodulin antagonists, naphthalene sulfonamide derivatives W-7 and W-13, to assess calmodulin activation of K+ and Cl- conductance in these two models. L-Ala swelling and subsequent RVD was not influenced by 25 microM W-7; hypotonic RVD was prevented by 25 microM W-7 or 100 microM W-13. The W-13 inhibition of RVD was by-passed with 0.5 microM gramicidin. Our data show that hypotonic RVD requires extracellular Ca2+ and that the K+ conductance activated is not charybdotoxin sensitive but requires calmodulin.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Differences in Ca(2+)-mediation of hypotonic and Na(+)-nutrient regulatory volume decrease in suspensions of jejunal enterocytes. We determined differences in the Ca2+ signalling of K+ and Cl- conductances required for Regulatory Volume Decrease (RVD) in jejunal villus enterocytes passively swollen (0.5 or 0.95.isotonic) compared with swelling because of the absorption of D-glucose (D-Glc) or L-Alanine (L-Ala). Cell volume was measured using electronic cell sizing. In nominally Ca(2+)-free medium containing EGTA (100 microM) RVD after 0.5 or 0.95.isotonic challenge was prevented. L-Ala swelling and subsequent RVD was influenced in Ca(2+)-free medium. Villus cells were incubated with 10 microM of the acetomethoxy derivative of 1,2.bis (2-aminophenoxy) ethane N,N,N1,N1 tetracetic acid (BAPTA-AM) and RVD after 0.5.isotonic swelling or L-Ala swelling was prevented. Niguldipine (0.1 microM), nifedipine (5 microM), diltiazem (100 microM), Ni2+, and Co2+ (1 mM) all prevented hypotonic RVD but had no effect on RVD after L-Ala addition. Charybdotoxin (25 nM) a potent inhibitor of Ca(2+)-activated K+ channels, had no effect on hypotonic RVD but prevented RVD of villus cells swollen by D-Glc. We used the calmodulin antagonists, naphthalene sulfonamide derivatives W-7 and W-13, to assess calmodulin activation of K+ and Cl- conductance in these two models. L-Ala swelling and subsequent RVD was not influenced by 25 microM W-7; hypotonic RVD was prevented by 25 microM W-7 or 100 microM W-13. The W-13 inhibition of RVD was by-passed with 0.5 microM gramicidin. Our data show that hypotonic RVD requires extracellular Ca2+ and that the K+ conductance activated is not charybdotoxin sensitive but requires calmodulin.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1281884", "title": "Spontaneous activity of the light-dependent channel irreversibly induced in excised patches from Limulus ventral photoreceptors.", "content": "We have studied the properties of membrane patches excised from the transducing lobe of Limulus ventral photoreceptors. If patches are excised into an \"internal\" solution that resembles the ionic composition of the cytoplasm, channel activity is typically absent, but can be turned on by cyclic GMP (cGMP). In contrast, if patches are excised directly into sea water and subsequently examined in internal solution, they exhibit a high channel activity in the absence of any second messenger (spontaneous channel activity). Because these patches contained only light-dependent channels when examined before excision and because these spontaneous channels have properties in common with the light/cGMP-dependent channel, we believe that the spontaneously active channels represent light/cGMP-dependent channels that have been damaged by exposure to sea water, perhaps due to proteolysis activated by the high Ca2+ levels of the sea water. One type of the spontaneously active channel resembles the light/cGMP-dependent channel in open time, reversal potential, conductance states and voltage dependence. Application of micromolar Ca2+ to this channel produces a reversible decrease in the opening rate, indicating a high affinity binding site for Ca2+ on this channel. Another type of spontaneously active channel has a conductance state and reversal potential similar to the light/cGMP-dependent channel, but has apparently lost its dependence and sensitivity to Ca2+ and voltage.", "contents": "Spontaneous activity of the light-dependent channel irreversibly induced in excised patches from Limulus ventral photoreceptors. We have studied the properties of membrane patches excised from the transducing lobe of Limulus ventral photoreceptors. If patches are excised into an \"internal\" solution that resembles the ionic composition of the cytoplasm, channel activity is typically absent, but can be turned on by cyclic GMP (cGMP). In contrast, if patches are excised directly into sea water and subsequently examined in internal solution, they exhibit a high channel activity in the absence of any second messenger (spontaneous channel activity). Because these patches contained only light-dependent channels when examined before excision and because these spontaneous channels have properties in common with the light/cGMP-dependent channel, we believe that the spontaneously active channels represent light/cGMP-dependent channels that have been damaged by exposure to sea water, perhaps due to proteolysis activated by the high Ca2+ levels of the sea water. One type of the spontaneously active channel resembles the light/cGMP-dependent channel in open time, reversal potential, conductance states and voltage dependence. Application of micromolar Ca2+ to this channel produces a reversible decrease in the opening rate, indicating a high affinity binding site for Ca2+ on this channel. Another type of spontaneously active channel has a conductance state and reversal potential similar to the light/cGMP-dependent channel, but has apparently lost its dependence and sensitivity to Ca2+ and voltage."} {"id": "PMID:1281885", "title": "cAMP activation of CF-affected Cl- conductance in both cell membranes of an absorptive epithelium.", "content": "Cystic fibrosis (CF) is characterized by abnormal epithelial Cl- conductance (GCl). In vitro studies that have shown that cAMP regulation is an intrinsic property of the CF-affected GCl(CF-GCl) have been carried out previously on cultured secretory cells and on nonepithelial cells. Even though GCl in absorption is defective in CF, a clear demonstration of cAMP regulation of CF-GCl in a purely absorptive tissue is lacking. We studied the cAMP regulation of CF-GCl in the microperfused intact human reabsorptive sweat duct. About 40% of the ducts responded to cAMP (responsive) while the remainder of the ducts did not. In responsive ducts, cAMP-elevating agents: beta-adrenergic agonist isoproterenol (IPR), CPT-cAMP, forskolin, theophylline or IBMX increased Gt by about 2.3-fold (n = no. of ducts = 8). Removal of media Cl-, but not amiloride pretreatment (in the lumen), abolished the cAMP response, indicating exclusive activation of GCl. cAMP activated both apical and basolateral GCl. cAMP hyperpolarized gluconate: Cl- (lumen:bath) transepithelial bionic potentials (delta Vt = -20.3 +/- 5.2 mV, mean +/- SE, n = 9) and transepithelial 3: 1 luminal NaCl dilution diffusion potentials (delta Vt = -8.8 +/- 2.9 mV, n = 5). cAMP activated basolateral GCl as indicated by increased bi-ionic (gluconate:Cl-, bath:lumen) diffusion potentials (by about 12 mV). The voltage divider ratio in symmetric NaCl solutions increased by 60%. Compared to responsive ducts, nonresponsive ducts were characterized by smaller spontaneous transepithelial potentials in symmetrical Ringer's solution (Vt = -6.9 +/- 0.8 mV, n = 24, nonresponsive vs. -19.4 +/- 1.8 mV, n = 22, responsive ducts) but larger bi-ionic potentials (-94 +/- 6 mV, n = 35, nonresponsive vs. -65 +/- 5 mV, n = 17, responsive ducts) and dilution diffusion potentials (-40 +/- 5 mV, n = 11, nonresponsive vs. -29 +/- 3 mV, n = 7, responsive ducts). These results are consistent with an inherently (prestimulus) maximal activation of GCl in nonresponsive ducts and submaximal activation of GCl in responsive ducts. We conclude that cAMP activates CF-GCl which is expressed and abnormal in both apical and basal membranes of this absorptive epithelium in CF.", "contents": "cAMP activation of CF-affected Cl- conductance in both cell membranes of an absorptive epithelium. Cystic fibrosis (CF) is characterized by abnormal epithelial Cl- conductance (GCl). In vitro studies that have shown that cAMP regulation is an intrinsic property of the CF-affected GCl(CF-GCl) have been carried out previously on cultured secretory cells and on nonepithelial cells. Even though GCl in absorption is defective in CF, a clear demonstration of cAMP regulation of CF-GCl in a purely absorptive tissue is lacking. We studied the cAMP regulation of CF-GCl in the microperfused intact human reabsorptive sweat duct. About 40% of the ducts responded to cAMP (responsive) while the remainder of the ducts did not. In responsive ducts, cAMP-elevating agents: beta-adrenergic agonist isoproterenol (IPR), CPT-cAMP, forskolin, theophylline or IBMX increased Gt by about 2.3-fold (n = no. of ducts = 8). Removal of media Cl-, but not amiloride pretreatment (in the lumen), abolished the cAMP response, indicating exclusive activation of GCl. cAMP activated both apical and basolateral GCl. cAMP hyperpolarized gluconate: Cl- (lumen:bath) transepithelial bionic potentials (delta Vt = -20.3 +/- 5.2 mV, mean +/- SE, n = 9) and transepithelial 3: 1 luminal NaCl dilution diffusion potentials (delta Vt = -8.8 +/- 2.9 mV, n = 5). cAMP activated basolateral GCl as indicated by increased bi-ionic (gluconate:Cl-, bath:lumen) diffusion potentials (by about 12 mV). The voltage divider ratio in symmetric NaCl solutions increased by 60%. Compared to responsive ducts, nonresponsive ducts were characterized by smaller spontaneous transepithelial potentials in symmetrical Ringer's solution (Vt = -6.9 +/- 0.8 mV, n = 24, nonresponsive vs. -19.4 +/- 1.8 mV, n = 22, responsive ducts) but larger bi-ionic potentials (-94 +/- 6 mV, n = 35, nonresponsive vs. -65 +/- 5 mV, n = 17, responsive ducts) and dilution diffusion potentials (-40 +/- 5 mV, n = 11, nonresponsive vs. -29 +/- 3 mV, n = 7, responsive ducts). These results are consistent with an inherently (prestimulus) maximal activation of GCl in nonresponsive ducts and submaximal activation of GCl in responsive ducts. We conclude that cAMP activates CF-GCl which is expressed and abnormal in both apical and basal membranes of this absorptive epithelium in CF."} {"id": "PMID:1281886", "title": "Gating of retinal rod cation channel by different nucleotides: comparative study of unitary currents.", "content": "Single channels are observed after incorporation of native vesicles from bovine rod outer segment membranes into planar lipid bilayers. The activity of a single channel in the presence of cGMP is compared to that induced by the analog 8-bromo-cGMP and by cAMP. At +80 mV, K0.5 is about 3 microM for 8Br-cGMP, 18 microM for cGMP and 740 microM for cAMP. In cAMP, the amplitude of the current is smaller than in cGMP or 8Br-cGMP and depends on the filter cut-off frequency. The open/closed transition rates of the channel are slightly slower with 8Br-cGMP than with cGMP while they are 5 to 10 times faster with cAMP. Addition of Ni2+ ions to either cGMP or cAMP increases the open probability: the open/closed transition rates and amplitude of the current in cAMP are then comparable to those in cGMP. A dual effect of the addition of cAMP on the cGMP- or 8Br-cGMP-dependent activity previously reported (Furman, R.E., Tanaka, J.C. 1989. Biochemistry 28:2785-2788) is observed with a single channel: addition of subthreshold cAMP concentrations to cGMP (or to 8Br-cGMP) markedly increases Po; addition of cAMP concentrations higher than about 70 microM progressively accelerates the kinetics and reduces the amplitude to values observed in cAMP alone. The results are discussed in relation with the model previously proposed to account for the existence of four current levels (Ildefonse, M., Bennett, N. 1991. J. Membrane Biol. 123:133-147).", "contents": "Gating of retinal rod cation channel by different nucleotides: comparative study of unitary currents. Single channels are observed after incorporation of native vesicles from bovine rod outer segment membranes into planar lipid bilayers. The activity of a single channel in the presence of cGMP is compared to that induced by the analog 8-bromo-cGMP and by cAMP. At +80 mV, K0.5 is about 3 microM for 8Br-cGMP, 18 microM for cGMP and 740 microM for cAMP. In cAMP, the amplitude of the current is smaller than in cGMP or 8Br-cGMP and depends on the filter cut-off frequency. The open/closed transition rates of the channel are slightly slower with 8Br-cGMP than with cGMP while they are 5 to 10 times faster with cAMP. Addition of Ni2+ ions to either cGMP or cAMP increases the open probability: the open/closed transition rates and amplitude of the current in cAMP are then comparable to those in cGMP. A dual effect of the addition of cAMP on the cGMP- or 8Br-cGMP-dependent activity previously reported (Furman, R.E., Tanaka, J.C. 1989. Biochemistry 28:2785-2788) is observed with a single channel: addition of subthreshold cAMP concentrations to cGMP (or to 8Br-cGMP) markedly increases Po; addition of cAMP concentrations higher than about 70 microM progressively accelerates the kinetics and reduces the amplitude to values observed in cAMP alone. The results are discussed in relation with the model previously proposed to account for the existence of four current levels (Ildefonse, M., Bennett, N. 1991. J. Membrane Biol. 123:133-147)."} {"id": "PMID:1281887", "title": "Structure of RNA and DNA chains in paused transcription complexes containing Escherichia coli RNA polymerase.", "content": "RNA polymerases pause conspicuously at certain positions on a DNA template. At the well-studied pause sites in the attenuation control regions that precede the trp and his operons, both formation of secondary structure in the nascent transcript and the DNA sequence immediately downstream contribute to pausing. The mechanisms of these effects are unknown. We report here studies on the structure of the RNA and DNA strands in purified trp and his paused transcription complexes in comparison to ten elongation complexes halted by nucleoside triphosphate deprivation. A 14 to 22 nucleotide region of the DNA strands was accessible to modification by KMnO4 or diethylpyrocarbonate in both the paused and halted transcription complexes. However, the region in front of the nucleotide-addition site was reactive only in some halted complexes. In both types of complexes, approximately eight nucleotides on the template strand immediately preceding the 3' end were protected from modification. We also examined the sensitivity of the nascent transcript to RNase A and found that the 3'-proximal eight nucleotide region could be cleaved without complete loss of the potential for elongation. However, a model RNA:DNA hybrid designed to mimic a hybrid in the transcription complex could also be cleaved under similar conditions. Together, the results suggest that the 3'-proximal eight nucleotides of transcript may pair with the DNA template and that this structure is not disrupted by hairpin formation at a pause site. Rather, pausing may result from distinct interactions between RNA polymerase and both the pause RNA hairpin and the downstream DNA sequence.", "contents": "Structure of RNA and DNA chains in paused transcription complexes containing Escherichia coli RNA polymerase. RNA polymerases pause conspicuously at certain positions on a DNA template. At the well-studied pause sites in the attenuation control regions that precede the trp and his operons, both formation of secondary structure in the nascent transcript and the DNA sequence immediately downstream contribute to pausing. The mechanisms of these effects are unknown. We report here studies on the structure of the RNA and DNA strands in purified trp and his paused transcription complexes in comparison to ten elongation complexes halted by nucleoside triphosphate deprivation. A 14 to 22 nucleotide region of the DNA strands was accessible to modification by KMnO4 or diethylpyrocarbonate in both the paused and halted transcription complexes. However, the region in front of the nucleotide-addition site was reactive only in some halted complexes. In both types of complexes, approximately eight nucleotides on the template strand immediately preceding the 3' end were protected from modification. We also examined the sensitivity of the nascent transcript to RNase A and found that the 3'-proximal eight nucleotide region could be cleaved without complete loss of the potential for elongation. However, a model RNA:DNA hybrid designed to mimic a hybrid in the transcription complex could also be cleaved under similar conditions. Together, the results suggest that the 3'-proximal eight nucleotides of transcript may pair with the DNA template and that this structure is not disrupted by hairpin formation at a pause site. Rather, pausing may result from distinct interactions between RNA polymerase and both the pause RNA hairpin and the downstream DNA sequence."} {"id": "PMID:1281889", "title": "Biosynthesis and expression of the myelin-associated glycoprotein in cultured oligodendrocytes from adult bovine brain.", "content": "The biosynthesis and expression of myelin-associated glycoprotein (MAG) were investigated in cultured oligodendrocytes isolated from adult bovine brain. Western blotting revealed two prominent MAG bands that were present in comparable amounts; the larger component electrophoresed above the 97 kD standard but was slightly smaller than the MAG band in purified bovine myelin, and the smaller component electrophoresed below the 97 kD standard. In comparison to other precursors of oligosaccharides, inorganic [35S]sulfate was a relatively specific isotope for labeling MAG relative to other glycoproteins in the cells. Sulfate labeled only the larger of the two MAG components, which contains complex N-linked oligosaccharides, but which appears to be glycosylated to a lesser extent than MAG in vivo. The smaller MAG band in the cells is a form with high-mannose oligosaccharides and was not detected in purified bovine myelin. Both the large and small MAG components were expressed on the oligodendrocyte surface as indicated by their sensitivity to neuraminidase and/or trypsin treatment of live cells. MAG was also released by the oligodendrocytes into the culture medium. The MAG in the medium was slightly smaller than that in the cells, suggesting that it may be released from the cell surface by limited proteolysis. The release of MAG by myelin-forming cells could be relevant to physiological roles that have been postulated for soluble forms of MAG and other adhesion proteins.", "contents": "Biosynthesis and expression of the myelin-associated glycoprotein in cultured oligodendrocytes from adult bovine brain. The biosynthesis and expression of myelin-associated glycoprotein (MAG) were investigated in cultured oligodendrocytes isolated from adult bovine brain. Western blotting revealed two prominent MAG bands that were present in comparable amounts; the larger component electrophoresed above the 97 kD standard but was slightly smaller than the MAG band in purified bovine myelin, and the smaller component electrophoresed below the 97 kD standard. In comparison to other precursors of oligosaccharides, inorganic [35S]sulfate was a relatively specific isotope for labeling MAG relative to other glycoproteins in the cells. Sulfate labeled only the larger of the two MAG components, which contains complex N-linked oligosaccharides, but which appears to be glycosylated to a lesser extent than MAG in vivo. The smaller MAG band in the cells is a form with high-mannose oligosaccharides and was not detected in purified bovine myelin. Both the large and small MAG components were expressed on the oligodendrocyte surface as indicated by their sensitivity to neuraminidase and/or trypsin treatment of live cells. MAG was also released by the oligodendrocytes into the culture medium. The MAG in the medium was slightly smaller than that in the cells, suggesting that it may be released from the cell surface by limited proteolysis. The release of MAG by myelin-forming cells could be relevant to physiological roles that have been postulated for soluble forms of MAG and other adhesion proteins."} {"id": "PMID:1281890", "title": "Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes.", "content": "Pharmacological characterization of the action of the novel non-N-methyl-D-aspartate (non-NMDA) antagonist AMOA (2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionate) on glutamate receptors was investigated in Xenopus oocytes injected with mouse brain mRNA. AMOA (150 microM) produced a nearly parallel shift to the right of the dose-response curve for kainate-induced currents. AMOA was found to have two different effects on AMPA receptors: 1) currents elicited by low concentrations of AMPA (6 microM) were inhibited by AMOA with an IC50 value of 160 +/- 19 microM and 2) currents elicited by high concentrations of AMPA (100 microM) were potentiated with an IC50 value of 88 +/- 22 microM. The maximal potentiating effect of AMOA on AMPA currents was around 170%. Furthermore, the two opposing effects of AMOA on AMPA responses are specific for the L-configuration of AMOA. This unusual antagonistic/agonistic property of AMOA may explain its unusual properties with regard to antagonism of non-NMDA receptor-mediated events previously described.", "contents": "Stereoselective effects of AMOA on non-NMDA receptors expressed in Xenopus oocytes. Pharmacological characterization of the action of the novel non-N-methyl-D-aspartate (non-NMDA) antagonist AMOA (2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionate) on glutamate receptors was investigated in Xenopus oocytes injected with mouse brain mRNA. AMOA (150 microM) produced a nearly parallel shift to the right of the dose-response curve for kainate-induced currents. AMOA was found to have two different effects on AMPA receptors: 1) currents elicited by low concentrations of AMPA (6 microM) were inhibited by AMOA with an IC50 value of 160 +/- 19 microM and 2) currents elicited by high concentrations of AMPA (100 microM) were potentiated with an IC50 value of 88 +/- 22 microM. The maximal potentiating effect of AMOA on AMPA currents was around 170%. Furthermore, the two opposing effects of AMOA on AMPA responses are specific for the L-configuration of AMOA. This unusual antagonistic/agonistic property of AMOA may explain its unusual properties with regard to antagonism of non-NMDA receptor-mediated events previously described."} {"id": "PMID:1281891", "title": "Interleukin-2 inhibits the GABA-induced Cl- current in identified Aplysia neurons.", "content": "The effects of extracellularly applied recombinant human interleukin-2 (rhIL-2) on the gamma-aminobutyric acid (GABA)-induced Cl- current recorded from identified neurons (R9 and R12) of Aplysia kurodai were investigated with conventional voltage-clamp and pressure ejection techniques. Bath-applied rhIL-2 (10-40 U/ml) reduced the GABA-induced current in the neurons without affecting resting membrane conductance and the holding current. The suppressing effect of rhIL-2 on the current was completely reversible. Heat-inactivated rhIL-2 was without effect. These results suggest that the immunomodulator IL-2 can modulate the GABA-induced response in the nervous system.", "contents": "Interleukin-2 inhibits the GABA-induced Cl- current in identified Aplysia neurons. The effects of extracellularly applied recombinant human interleukin-2 (rhIL-2) on the gamma-aminobutyric acid (GABA)-induced Cl- current recorded from identified neurons (R9 and R12) of Aplysia kurodai were investigated with conventional voltage-clamp and pressure ejection techniques. Bath-applied rhIL-2 (10-40 U/ml) reduced the GABA-induced current in the neurons without affecting resting membrane conductance and the holding current. The suppressing effect of rhIL-2 on the current was completely reversible. Heat-inactivated rhIL-2 was without effect. These results suggest that the immunomodulator IL-2 can modulate the GABA-induced response in the nervous system."} {"id": "PMID:1281892", "title": "[Complete remission with MEC regimen of acute myeloid leukemia (M4) secondary to 5-year treatment of non-Hodgkin lymphoma].", "content": "A 32-year-old woman was admitted to our hospital with pyrexia and general lymphadenopathy in July 1984. She was diagnosed as having malignant lymphoma (follicular, small cleaved cell), stage IV based on the histological findings of lymph nodes in the neck and bone marrow specimen. She was treated with melphalan orally for 3 years, followed by MACOP-B. She attained partial remission with MACOP-B. Thereafter, she received melphalan or Endoxan orally as maintenance therapy. She developed fever and swelling in the gingivae in October 1989. Peripheral blood showed WBC 80,200/microliters with 7.5% myeloblasts and 85.5% monocytes. Bone marrow aspirate revealed hypercellularity with 47.9% myeloblasts, 46.5% monoblasts and monocytes, which were positive for peroxidase and NSE stains. The karyotype of bone marrow cells showed a 46,XX,t(9;11). The lysozyme in serum was elevated. She was diagnosed having AML (M4). DCMP regimen was initiated but failed to achieve CR. Consequently she received MEC regimen and obtained complete remission, lasting for 6 months. Patients with second leukemia have a low probability of achieving complete remission using conventional chemotherapy. The MEC regimen is thought to be one of the most promising treatments for secondary leukemia.", "contents": "[Complete remission with MEC regimen of acute myeloid leukemia (M4) secondary to 5-year treatment of non-Hodgkin lymphoma]. A 32-year-old woman was admitted to our hospital with pyrexia and general lymphadenopathy in July 1984. She was diagnosed as having malignant lymphoma (follicular, small cleaved cell), stage IV based on the histological findings of lymph nodes in the neck and bone marrow specimen. She was treated with melphalan orally for 3 years, followed by MACOP-B. She attained partial remission with MACOP-B. Thereafter, she received melphalan or Endoxan orally as maintenance therapy. She developed fever and swelling in the gingivae in October 1989. Peripheral blood showed WBC 80,200/microliters with 7.5% myeloblasts and 85.5% monocytes. Bone marrow aspirate revealed hypercellularity with 47.9% myeloblasts, 46.5% monoblasts and monocytes, which were positive for peroxidase and NSE stains. The karyotype of bone marrow cells showed a 46,XX,t(9;11). The lysozyme in serum was elevated. She was diagnosed having AML (M4). DCMP regimen was initiated but failed to achieve CR. Consequently she received MEC regimen and obtained complete remission, lasting for 6 months. Patients with second leukemia have a low probability of achieving complete remission using conventional chemotherapy. The MEC regimen is thought to be one of the most promising treatments for secondary leukemia."} {"id": "PMID:1281893", "title": "[The successful treatment of G-CSF in autoimmune neutropenia with liver cirrhosis complicated by esophageal varices].", "content": "A 72 year-old woman was admitted to our hospital for hematoemesis. After admission, endoscopic examination showed esophageal varices with a red color sign which indicated endoscopic injection sclerotherapy (EIS). Concurrently, however, laboratory findings revealed severe neutropenia in peripheral blood, while bone marrow examination showed marked reduction of mature granulocytes with mild myeloid hyperplasia. As a result of those hematological abnormalities, EIS was halted. Concerning the pathogenesis of this neutropenia, immunofluorescence technique using flow cytometry disclosed the presence of anti-neutrophil autoantibody in the serum, giving a clinical diagnosis of autoimmune neutropenia (AIN). Thereafter, a conventional regimen of corticosteroids as an initial therapy and steroid pulse therapy as a succeeding maneuver were instituted, but in vain. As a last resort, 125 micrograms/body of rhG-CSF was given daily subcutaneously. As a consequence, significant increase in granulocyte count, though transient, was attained, which made EIS possible without any episodes of infections. It seems most likely that a high dose of rhG-CSF exerts beneficial effects as a prophylactic and therapeutic regimen against infections in patients with AIN.", "contents": "[The successful treatment of G-CSF in autoimmune neutropenia with liver cirrhosis complicated by esophageal varices]. A 72 year-old woman was admitted to our hospital for hematoemesis. After admission, endoscopic examination showed esophageal varices with a red color sign which indicated endoscopic injection sclerotherapy (EIS). Concurrently, however, laboratory findings revealed severe neutropenia in peripheral blood, while bone marrow examination showed marked reduction of mature granulocytes with mild myeloid hyperplasia. As a result of those hematological abnormalities, EIS was halted. Concerning the pathogenesis of this neutropenia, immunofluorescence technique using flow cytometry disclosed the presence of anti-neutrophil autoantibody in the serum, giving a clinical diagnosis of autoimmune neutropenia (AIN). Thereafter, a conventional regimen of corticosteroids as an initial therapy and steroid pulse therapy as a succeeding maneuver were instituted, but in vain. As a last resort, 125 micrograms/body of rhG-CSF was given daily subcutaneously. As a consequence, significant increase in granulocyte count, though transient, was attained, which made EIS possible without any episodes of infections. It seems most likely that a high dose of rhG-CSF exerts beneficial effects as a prophylactic and therapeutic regimen against infections in patients with AIN."} {"id": "PMID:1281894", "title": "The potential for the development of liver metastasis from alpha-fetoprotein-producing human gastric carcinomas in nude mice.", "content": "The potential for liver metastasis in addition to the transplantability and doubling time of alpha-fetoprotein(AFP)-producing and non-AFP-producing human gastric carcinomas were studied in nude mice. The potential for liver metastasis was analyzed histopathologically from intrasplenic injections of tumor cell suspensions prepared from subcutaneous tumors. Tumor fragments prepared aseptically from 15 AFP-producing and 140 non-AFP-producing gastric cancers were subcutaneously transplanted into nude mice with transplantability rates of 80% (12/15 cases) and 50% (70/140 cases), respectively. The mean tumor doubling times in the first generation were 10.6 days for AFP-producing and 13.2 days for non-AFP-producing gastric carcinomas. Serially transplantable tumor lines in nude mice were established from six AFP-producing and 10 non-AFP-producing carcinomas. When tumor cell suspensions prepared from the subcutaneous tumors were injected into spleens, all six AFP-producing carcinomas (two poorly differentiated and four tubular adenocarcinomas) but only four out of the 10 non-AFP-producing carcinomas (two poorly differentiated adenocarcinomas, one mucinous carcinoma and one papillary adenocarcinoma) demonstrated a potential for liver metastasis. The results indicate AFP-producing gastric carcinomas to possess a higher potential for liver metastasis than do non-AFP-producing carcinomas, a distinguishing feature which thus reflects a poor prognosis.", "contents": "The potential for the development of liver metastasis from alpha-fetoprotein-producing human gastric carcinomas in nude mice. The potential for liver metastasis in addition to the transplantability and doubling time of alpha-fetoprotein(AFP)-producing and non-AFP-producing human gastric carcinomas were studied in nude mice. The potential for liver metastasis was analyzed histopathologically from intrasplenic injections of tumor cell suspensions prepared from subcutaneous tumors. Tumor fragments prepared aseptically from 15 AFP-producing and 140 non-AFP-producing gastric cancers were subcutaneously transplanted into nude mice with transplantability rates of 80% (12/15 cases) and 50% (70/140 cases), respectively. The mean tumor doubling times in the first generation were 10.6 days for AFP-producing and 13.2 days for non-AFP-producing gastric carcinomas. Serially transplantable tumor lines in nude mice were established from six AFP-producing and 10 non-AFP-producing carcinomas. When tumor cell suspensions prepared from the subcutaneous tumors were injected into spleens, all six AFP-producing carcinomas (two poorly differentiated and four tubular adenocarcinomas) but only four out of the 10 non-AFP-producing carcinomas (two poorly differentiated adenocarcinomas, one mucinous carcinoma and one papillary adenocarcinoma) demonstrated a potential for liver metastasis. The results indicate AFP-producing gastric carcinomas to possess a higher potential for liver metastasis than do non-AFP-producing carcinomas, a distinguishing feature which thus reflects a poor prognosis."} {"id": "PMID:1281895", "title": "Establishment of large cell lung cancer cell lines secreting hematopoietic factors inducing leukocytosis and thrombocytosis.", "content": "We have established cell lines from a large cell carcinoma of the lung accompanied by marked granulocytosis and thrombocytosis, and have analyzed the factors with colony stimulating factor (CSF) activity produced by them. Analysis of the CSF activity present in the culture medium of the established cell lines demonstrated growth-stimulating activity on CMK cells, a human megakaryoblastic cell line and mouse bone marrow cells. A neutralization test with antibodies against G-, M- and GM-CSF indicated the stimulation for the proliferation of CMK and mouse bone marrow cells to be mediated partially by the CSFs. Furthermore, the measurement of GM-CSF and interleukin(IL)6 by enzyme-linked immunosorbent assay (ELISA) and northern blotting analysis indicated productions of G-, GM- and M-CSF and of IL6 from the cell lines but failed to exhibit IL3 gene expression. It is suggested that the cell lines could be of use in the study of CSFs and, also, that lymphokines act on leukocyte and platelet progenitor cells.", "contents": "Establishment of large cell lung cancer cell lines secreting hematopoietic factors inducing leukocytosis and thrombocytosis. We have established cell lines from a large cell carcinoma of the lung accompanied by marked granulocytosis and thrombocytosis, and have analyzed the factors with colony stimulating factor (CSF) activity produced by them. Analysis of the CSF activity present in the culture medium of the established cell lines demonstrated growth-stimulating activity on CMK cells, a human megakaryoblastic cell line and mouse bone marrow cells. A neutralization test with antibodies against G-, M- and GM-CSF indicated the stimulation for the proliferation of CMK and mouse bone marrow cells to be mediated partially by the CSFs. Furthermore, the measurement of GM-CSF and interleukin(IL)6 by enzyme-linked immunosorbent assay (ELISA) and northern blotting analysis indicated productions of G-, GM- and M-CSF and of IL6 from the cell lines but failed to exhibit IL3 gene expression. It is suggested that the cell lines could be of use in the study of CSFs and, also, that lymphokines act on leukocyte and platelet progenitor cells."} {"id": "PMID:1281896", "title": "Frequent association of Epstein-Barr virus in Japanese patients with Burkitt's lymphoma.", "content": "Seven Japanese patients with Burkitt's lymphoma (BL), residing in Hokkaido, were studied during the period, 1979-1991. Immunological analyses of their lymphoma cells showed all to express surface and/or cytoplasmic immunoglobulins. Chromosomal analysis was performed in five cases. Four of the five lymphomas had the chromosomal translocation, t(8;14), and one had t(2;8). Three patients had extremely high IgG antibody titers to Epstein-Barr virus (EBV) viral capsid antigen (VCA) and to EBV early antigens (EA). Two patients had positive antibodies to EA, and two others had normal antibody patterns comparable to those of EBV-seropositive age- and sex-matched healthy controls. Four of the seven lymphomas (57.1%) were positive for EBV-determined nuclear antigen (EBNA) by anticomplement immunofluorescence and/or EBV DNA using DNA-DNA reassociation kinetics, and/or Southern blot analysis. The frequency of EBV positivity in BL patients residing in Hokkaido was higher than that of cases previously reported in Japan. Three of the four EBV genome-positive BL patients responded well to chemotherapy, radiotherapy and/or surgical treatment, with no significant relapse being observed during the study period. In contrast, EBV genome-negative patients had poor prognoses despite having similar levels of clinical staging at the time of diagnosis.", "contents": "Frequent association of Epstein-Barr virus in Japanese patients with Burkitt's lymphoma. Seven Japanese patients with Burkitt's lymphoma (BL), residing in Hokkaido, were studied during the period, 1979-1991. Immunological analyses of their lymphoma cells showed all to express surface and/or cytoplasmic immunoglobulins. Chromosomal analysis was performed in five cases. Four of the five lymphomas had the chromosomal translocation, t(8;14), and one had t(2;8). Three patients had extremely high IgG antibody titers to Epstein-Barr virus (EBV) viral capsid antigen (VCA) and to EBV early antigens (EA). Two patients had positive antibodies to EA, and two others had normal antibody patterns comparable to those of EBV-seropositive age- and sex-matched healthy controls. Four of the seven lymphomas (57.1%) were positive for EBV-determined nuclear antigen (EBNA) by anticomplement immunofluorescence and/or EBV DNA using DNA-DNA reassociation kinetics, and/or Southern blot analysis. The frequency of EBV positivity in BL patients residing in Hokkaido was higher than that of cases previously reported in Japan. Three of the four EBV genome-positive BL patients responded well to chemotherapy, radiotherapy and/or surgical treatment, with no significant relapse being observed during the study period. In contrast, EBV genome-negative patients had poor prognoses despite having similar levels of clinical staging at the time of diagnosis."} {"id": "PMID:1281897", "title": "A simple and reliable method for the detection and quantitation of the human T-cell leukemia virus type-I provirus in peripheral blood mononuclear cells of seropositive blood donors.", "content": "Human T-cell leukemia virus type I (HTLV-I) antibody detection has been widely used to screen HTLV-I carriers. Sometimes, however, it gives false positive or negative results. A demonstration of the HTLV-I provirus from patients' peripheral blood mononuclear cells (PBMC) should, therefore, give the crucial evidence for them being HTLV-I carriers. We established a simple and reliable method using the polymerase chain reaction (PCR) to detect one molecule of HTLV-I provirus in 100 x 10(3) PBMC, during which internal control primers for the human beta-globin gene were also employed in the same reaction tube to check the success of the amplification reaction. We can thus easily avoid any false negative judgement and quantitate the HTLV-I provirus in PBMC simply by diluting the sample before PCR. One ml blood was enough for ten or more determinations by PCR. Analysis of seropositive blood from donors demonstrated a wide range for the number of HTLV-I provirus in PBMC. The method could conveniently be used for quantitating HTLV-I proviruses and following up HTLV-I carriers to study the pathophysiology and mode of HTLV-I transmission.", "contents": "A simple and reliable method for the detection and quantitation of the human T-cell leukemia virus type-I provirus in peripheral blood mononuclear cells of seropositive blood donors. Human T-cell leukemia virus type I (HTLV-I) antibody detection has been widely used to screen HTLV-I carriers. Sometimes, however, it gives false positive or negative results. A demonstration of the HTLV-I provirus from patients' peripheral blood mononuclear cells (PBMC) should, therefore, give the crucial evidence for them being HTLV-I carriers. We established a simple and reliable method using the polymerase chain reaction (PCR) to detect one molecule of HTLV-I provirus in 100 x 10(3) PBMC, during which internal control primers for the human beta-globin gene were also employed in the same reaction tube to check the success of the amplification reaction. We can thus easily avoid any false negative judgement and quantitate the HTLV-I provirus in PBMC simply by diluting the sample before PCR. One ml blood was enough for ten or more determinations by PCR. Analysis of seropositive blood from donors demonstrated a wide range for the number of HTLV-I provirus in PBMC. The method could conveniently be used for quantitating HTLV-I proviruses and following up HTLV-I carriers to study the pathophysiology and mode of HTLV-I transmission."} {"id": "PMID:1281898", "title": "[Determination of exocrine pancreatic function in childhood with the pancreozymin-secretin test].", "content": "Pancreatic function can only be determined exactly via the pancreozymin-secretin test. We conducted this test in two versions: (1) under conditions of continuous perfusion with the possibility of volume correction and (2) as a simple tubing. We compared the results of 86 tubings with the results of 87 examinations under perfusion. For that purpose all patients were classified into four groups: group a) with 46 and 10 examinations, respectively, in patients suffering from cholestasis in early infancy, group b) with 7 and 12 examinations, respectively, in older patients with liver diseases, group c) with 8 and 17 examinations, respectively, in patients suffering from cystic fibrosis or Shwachman's syndrome and group d) with 25 and 48 examinations, respectively, in children with normal pancreatic function. Both examination methods nearly identical mean values of the enzyme activities in all four patient groups. However, mean variations were found to be higher in case of tubing. Therefore the lower limits (x - 2s) of this test were defined at a lower level than those of the tests under perfusion.", "contents": "[Determination of exocrine pancreatic function in childhood with the pancreozymin-secretin test]. Pancreatic function can only be determined exactly via the pancreozymin-secretin test. We conducted this test in two versions: (1) under conditions of continuous perfusion with the possibility of volume correction and (2) as a simple tubing. We compared the results of 86 tubings with the results of 87 examinations under perfusion. For that purpose all patients were classified into four groups: group a) with 46 and 10 examinations, respectively, in patients suffering from cholestasis in early infancy, group b) with 7 and 12 examinations, respectively, in older patients with liver diseases, group c) with 8 and 17 examinations, respectively, in patients suffering from cystic fibrosis or Shwachman's syndrome and group d) with 25 and 48 examinations, respectively, in children with normal pancreatic function. Both examination methods nearly identical mean values of the enzyme activities in all four patient groups. However, mean variations were found to be higher in case of tubing. Therefore the lower limits (x - 2s) of this test were defined at a lower level than those of the tests under perfusion."} {"id": "PMID:1281900", "title": "Cytoskeleton and other differentiation markers in the colon.", "content": "Differentiation of intestinal epithelial cells involves a complex process of establishment of cell polarity, commitment to cell lineage, and inhibition of cell division. Polarized epithelial cells are characterized by specific junctional complexes and cytoskeletal proteins which produce specific membrane domains. Intestinal cytoskeletal proteins are often preserved in neoplastic colonic tissues, and can be used to identify the cell of origin of poorly differentiated cancers. In this context, these proteins are markers of organ-specific differentiation. In addition, since loss of cytoskeletal polarity commonly occurs in transformed cells, aberrant expression of these proteins may be used as a marker of neoplasia in the colon. Normal polarization of basolateral proteins (secretory component) and apical proteins such as brush border hydrolases, cytoskeletal proteins (villin, fodrin), and carcinoembryonic antigen can become disrupted in adenomas and cancers. Cytoskeletal intermediate filaments (cytokeratins) demonstrate increased immunoreactivity in villous adenomas and cancers compared with normal colonic crypts. Altered actin bundles are found in preneoplastic mucosa such as colon from patients with familial polyposis coli. Molecular mechanisms responsible for altered cytoskeletal structures remain unclear; however, altered protein phosphorylation most likely plays a role. For example, the phosphorylation status of cytoskeletal and junctional complex proteins appears to influence their solubility and interactive properties, which may result in altered cell polarity. Markers of altered cytoskeletal structure and polarity can identify neoplastic colonocytes; however, the extent to which they can be used as intermediate markers of colonic neoplasia remains to be determined.", "contents": "Cytoskeleton and other differentiation markers in the colon. Differentiation of intestinal epithelial cells involves a complex process of establishment of cell polarity, commitment to cell lineage, and inhibition of cell division. Polarized epithelial cells are characterized by specific junctional complexes and cytoskeletal proteins which produce specific membrane domains. Intestinal cytoskeletal proteins are often preserved in neoplastic colonic tissues, and can be used to identify the cell of origin of poorly differentiated cancers. In this context, these proteins are markers of organ-specific differentiation. In addition, since loss of cytoskeletal polarity commonly occurs in transformed cells, aberrant expression of these proteins may be used as a marker of neoplasia in the colon. Normal polarization of basolateral proteins (secretory component) and apical proteins such as brush border hydrolases, cytoskeletal proteins (villin, fodrin), and carcinoembryonic antigen can become disrupted in adenomas and cancers. Cytoskeletal intermediate filaments (cytokeratins) demonstrate increased immunoreactivity in villous adenomas and cancers compared with normal colonic crypts. Altered actin bundles are found in preneoplastic mucosa such as colon from patients with familial polyposis coli. Molecular mechanisms responsible for altered cytoskeletal structures remain unclear; however, altered protein phosphorylation most likely plays a role. For example, the phosphorylation status of cytoskeletal and junctional complex proteins appears to influence their solubility and interactive properties, which may result in altered cell polarity. Markers of altered cytoskeletal structure and polarity can identify neoplastic colonocytes; however, the extent to which they can be used as intermediate markers of colonic neoplasia remains to be determined."} {"id": "PMID:1281899", "title": "[Surgical treatment of goiter in residents of the Kiev district].", "content": "The article characterizes the mortality rates of nodular and mixed euthyroid goiter in the Ukraine Republic and discusses the results of surgical treatment of 681 patients with various forms of goiter. In view of the double increase of the number of cases of thyroid carcinoma in the last 4 years, the authors suggest resecting the thyroid gland more extensively than in the previously conducted economical resections. Radioimmunological study of the thyroid hormones and thyrotropin in dynamics showed activation of hypophyseal +thyrotropic function after the operation. The authors, therefore, recommend using thyroidin without fail. Postoperative recurrences-1.5%, stable hypothyroidism-1.8%.", "contents": "[Surgical treatment of goiter in residents of the Kiev district]. The article characterizes the mortality rates of nodular and mixed euthyroid goiter in the Ukraine Republic and discusses the results of surgical treatment of 681 patients with various forms of goiter. In view of the double increase of the number of cases of thyroid carcinoma in the last 4 years, the authors suggest resecting the thyroid gland more extensively than in the previously conducted economical resections. Radioimmunological study of the thyroid hormones and thyrotropin in dynamics showed activation of hypophyseal +thyrotropic function after the operation. The authors, therefore, recommend using thyroidin without fail. Postoperative recurrences-1.5%, stable hypothyroidism-1.8%."} {"id": "PMID:1281901", "title": "Symbolic interactionism: a perspective for understanding parent-nurse interactions following the birth of a child with Down syndrome.", "content": "The birth of a child with Down syndrome is a challenge to parental and societal expectations. Feelings of shock, sadness, confusion, denial, fear, anger, guilt, and helplessness may be evoked. In this paper, the impact of stigma on individuals with Down syndrome and their families will be reviewed to clarify why interactions between parents and others need to be explored. Next, the central concepts important to the symbolic interactionist perspective will be reviewed. Then, qualitative data from an ongoing study of 90 parents of children with Down syndrome (ages 3 months to 18 years) will be presented to illustrate how symbolic interactionism can be applied to the to care of children with Down syndrome and their families. Finally, implications for nurses working with families that include a child with Down syndrome will be addressed.", "contents": "Symbolic interactionism: a perspective for understanding parent-nurse interactions following the birth of a child with Down syndrome. The birth of a child with Down syndrome is a challenge to parental and societal expectations. Feelings of shock, sadness, confusion, denial, fear, anger, guilt, and helplessness may be evoked. In this paper, the impact of stigma on individuals with Down syndrome and their families will be reviewed to clarify why interactions between parents and others need to be explored. Next, the central concepts important to the symbolic interactionist perspective will be reviewed. Then, qualitative data from an ongoing study of 90 parents of children with Down syndrome (ages 3 months to 18 years) will be presented to illustrate how symbolic interactionism can be applied to the to care of children with Down syndrome and their families. Finally, implications for nurses working with families that include a child with Down syndrome will be addressed."} {"id": "PMID:1281905", "title": "[Recurrence of Hodgkin's disease after advanced primary stages. German Hodgkin's Study Group].", "content": "In a multicentre study on the treatment of Hodgkin's disease, 88 out of 297 patients with primary advanced stages IIIB/IV failed to respond to alternating COPP/ABVD chemotherapy +/- radiotherapy. They may be broken down as follows: tumour progression under current therapy (PD) 23/28, partial remission at the end of treatment (PR) 28/88, early nodal recurrence 13/88, late nodal recurrence 15/88, extranodal recurrence 7/88, unclear localisation 1/88. Thirty-six months after noting failure of treatment, 45% of all patients were still alive. The prognosis was poorest in the case of primary PD. Only 1/23 of these patients experience lasting complete remission thanks to salvage treatment (cCR). Eleven patients with an exclusively nodal recurrence experienced a cCR on treatment with radiation alone, and may be considered a low-risk recurrence group. For a high-risk recurrence group (n = 57), indication for high-dose chemotherapy with subsequent autologous bone marrow transplantation (HDC/ABMT) should have been recognized on the basis of the present definition. The survival probability of these patients, who only received conventional salvage treatment, was 38% after 30 months (95% confidence limit, 22 to 54%). These data would not appear to be appreciably poorer than those reported in the literature for comparable patients receiving HDC/ABMT. Only a randomized comparison would be capable of showing whether HDC/ABMT is superior to high-dose conventional chemotherapy with haematopoietic growth factors. It is proposed that such a therapeutic trial should be initiated as soon as possible.", "contents": "[Recurrence of Hodgkin's disease after advanced primary stages. German Hodgkin's Study Group]. In a multicentre study on the treatment of Hodgkin's disease, 88 out of 297 patients with primary advanced stages IIIB/IV failed to respond to alternating COPP/ABVD chemotherapy +/- radiotherapy. They may be broken down as follows: tumour progression under current therapy (PD) 23/28, partial remission at the end of treatment (PR) 28/88, early nodal recurrence 13/88, late nodal recurrence 15/88, extranodal recurrence 7/88, unclear localisation 1/88. Thirty-six months after noting failure of treatment, 45% of all patients were still alive. The prognosis was poorest in the case of primary PD. Only 1/23 of these patients experience lasting complete remission thanks to salvage treatment (cCR). Eleven patients with an exclusively nodal recurrence experienced a cCR on treatment with radiation alone, and may be considered a low-risk recurrence group. For a high-risk recurrence group (n = 57), indication for high-dose chemotherapy with subsequent autologous bone marrow transplantation (HDC/ABMT) should have been recognized on the basis of the present definition. The survival probability of these patients, who only received conventional salvage treatment, was 38% after 30 months (95% confidence limit, 22 to 54%). These data would not appear to be appreciably poorer than those reported in the literature for comparable patients receiving HDC/ABMT. Only a randomized comparison would be capable of showing whether HDC/ABMT is superior to high-dose conventional chemotherapy with haematopoietic growth factors. It is proposed that such a therapeutic trial should be initiated as soon as possible."} {"id": "PMID:1281903", "title": "Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction.", "content": "Self-expanding metal stents are claimed to prolong biliary-stent patency, although no formal comparative trial between plastic and expandable stents has been done. In a prospective randomised trial, we assigned 105 patients with irresectable distal bile-duct malignancy to receive either a metal stent (49) or a straight polyethylene stent (56). Median patency of the first stent was significantly prolonged in patients with a metal stent compared with those with a polyethylene stent (273 vs 126 days; p = 0.006). The major cause of stent dysfunction was tumour ingrowth in the metal-stent group and sludge deposition in the polyethylene-stent group. Treatment after any occlusion included placement of a polyethylene stent. In the metal-stent group none of 14 second stents occluded, whereas 11 of 23 (48%) second stents clogged in the polyethylene-stent group (p = 0.002). Overall median survival was 149 days and did not differ significantly between treatment groups. Incremental cost-effectiveness analysis showed that initial placement of a metal stent results in a 28% decrease of endoscopic procedures. Self-expanding metal stents have a longer patency than polyethylene stents and offer adequate palliation in patients with irresectable malignant distal bile-duct obstruction.", "contents": "Randomised trial of self-expanding metal stents versus polyethylene stents for distal malignant biliary obstruction. Self-expanding metal stents are claimed to prolong biliary-stent patency, although no formal comparative trial between plastic and expandable stents has been done. In a prospective randomised trial, we assigned 105 patients with irresectable distal bile-duct malignancy to receive either a metal stent (49) or a straight polyethylene stent (56). Median patency of the first stent was significantly prolonged in patients with a metal stent compared with those with a polyethylene stent (273 vs 126 days; p = 0.006). The major cause of stent dysfunction was tumour ingrowth in the metal-stent group and sludge deposition in the polyethylene-stent group. Treatment after any occlusion included placement of a polyethylene stent. In the metal-stent group none of 14 second stents occluded, whereas 11 of 23 (48%) second stents clogged in the polyethylene-stent group (p = 0.002). Overall median survival was 149 days and did not differ significantly between treatment groups. Incremental cost-effectiveness analysis showed that initial placement of a metal stent results in a 28% decrease of endoscopic procedures. Self-expanding metal stents have a longer patency than polyethylene stents and offer adequate palliation in patients with irresectable malignant distal bile-duct obstruction."} {"id": "PMID:1281906", "title": "Evaluation of fetal cardiac arrhythmias. Ultrasound findings and neonatal outcome.", "content": "During a four-year period, 3,882 fetal diagnostic ultrasounds were performed and 162 patients (4% of all patients scanned) were referred to our perinatal center for evaluation of fetal cardiac arrhythmia. Fetal echocardiography subsequently revealed an arrhythmia in 80 (49%) of these patients. The rhythm disturbances noted were premature atrial or ventricular contractions (n = 65, 81%), tachyarrhythmia (n = 8, 10%), and bradyarrhythmia (n = 7, 9%). Three of the bradycardic fetuses evaluated had complete heart block associated with anatomic abnormalities. In seven tachycardic fetuses, the finding of fetal compromise was followed by intervention. The majority of fetuses with cardiac rhythm disturbance will have premature atrial or ventricular contractions and will have normal echocardiographic evaluation and neonatal outcome. Sustained tachyarrhythmias and bradyarrhythmias are more likely to be associated with fetal morbidity. Based upon the findings of this study and others, we propose a scheme for follow-up of the fetus referred with an irregular cardiac rhythm.", "contents": "Evaluation of fetal cardiac arrhythmias. Ultrasound findings and neonatal outcome. During a four-year period, 3,882 fetal diagnostic ultrasounds were performed and 162 patients (4% of all patients scanned) were referred to our perinatal center for evaluation of fetal cardiac arrhythmia. Fetal echocardiography subsequently revealed an arrhythmia in 80 (49%) of these patients. The rhythm disturbances noted were premature atrial or ventricular contractions (n = 65, 81%), tachyarrhythmia (n = 8, 10%), and bradyarrhythmia (n = 7, 9%). Three of the bradycardic fetuses evaluated had complete heart block associated with anatomic abnormalities. In seven tachycardic fetuses, the finding of fetal compromise was followed by intervention. The majority of fetuses with cardiac rhythm disturbance will have premature atrial or ventricular contractions and will have normal echocardiographic evaluation and neonatal outcome. Sustained tachyarrhythmias and bradyarrhythmias are more likely to be associated with fetal morbidity. Based upon the findings of this study and others, we propose a scheme for follow-up of the fetus referred with an irregular cardiac rhythm."} {"id": "PMID:1281907", "title": "[Study of surgical treatment and nonsurgical treatment as palliation for unresectable esophageal cancer].", "content": "A retrospective study was carried out to evaluate treatment in 24 patients with unresectable esophageal cancer who underwent bypass operation (group A; n = 11) or esophageal prosthesis intubation (group B; n = 13), regarding food intake, quality of life and survival. The results were as follows: 1) According to the preoperative or intraoperative findings, all the patients, except one case is group A, were diagnosed as A3 (2 case in group B had a esophago-bronchial fistula). 2) After surgery, oral food intake was possible in only 2 patients in group A, and intake of a regular diet was possible in all patients in group B, after intubation. 3) In group A, none of the patients except 1, could be discharged because of postoperative complication, and they died in the hospital. The mean postoperative survival period was 63 +/- 74 days. On the other hand, fatal complications were not observed in group B, and 8 patients were discharged from the hospital (2 of them could resume work). The mean survival period, including 1 survivor, was 136 +/- 101 days, that is significantly longer than that in group A (p < 0.05). From these results, we concluded that esophageal intubation is useful for cases of unresectable esophageal cancer.", "contents": "[Study of surgical treatment and nonsurgical treatment as palliation for unresectable esophageal cancer]. A retrospective study was carried out to evaluate treatment in 24 patients with unresectable esophageal cancer who underwent bypass operation (group A; n = 11) or esophageal prosthesis intubation (group B; n = 13), regarding food intake, quality of life and survival. The results were as follows: 1) According to the preoperative or intraoperative findings, all the patients, except one case is group A, were diagnosed as A3 (2 case in group B had a esophago-bronchial fistula). 2) After surgery, oral food intake was possible in only 2 patients in group A, and intake of a regular diet was possible in all patients in group B, after intubation. 3) In group A, none of the patients except 1, could be discharged because of postoperative complication, and they died in the hospital. The mean postoperative survival period was 63 +/- 74 days. On the other hand, fatal complications were not observed in group B, and 8 patients were discharged from the hospital (2 of them could resume work). The mean survival period, including 1 survivor, was 136 +/- 101 days, that is significantly longer than that in group A (p < 0.05). From these results, we concluded that esophageal intubation is useful for cases of unresectable esophageal cancer."} {"id": "PMID:1281910", "title": "Relationship between intestinal function and chloride secretion in patients with cystic fibrosis.", "content": "Cystic fibrosis (CF) is the most frequent inheritable disease with a lethal course. One of the major problems of the disease is malabsorption and malnutrition, due to pancreatic insufficiency which is already present at birth in more than 85% of the patients. Characteristically the mucoid secretion products of the epithelial tissues in lung, pancreas, liver and intestine have a high viscosity. The pathophysiology is characterized by obstruction of these organs with secondary damage and finally destruction. For a long period intestinal obstruction syndromes in CF were ascribed only to the pancreatic insufficiency. Malabsorption is not only caused by enzyme deficiency but is also related to transport processes to the surface of the enterocytes. This indicates that the intestinal disorders in CF are partly the result of mucoid plugging and not only of pancreatic insufficiency. Recently in vitro studies have shown a blockade of secretion through chloride channels in the mucosal membrane of CF tissues. In vivo measurements of chloride fluxes in the rectum showed a disturbed regulation in CF patients. The high viscosity of the mucus and plugging is directly related to the diminished chloride secretion. So it is postulated that the abnormal chloride secretion is responsible for the intestinal obstruction and partially also for the malabsorption.", "contents": "Relationship between intestinal function and chloride secretion in patients with cystic fibrosis. Cystic fibrosis (CF) is the most frequent inheritable disease with a lethal course. One of the major problems of the disease is malabsorption and malnutrition, due to pancreatic insufficiency which is already present at birth in more than 85% of the patients. Characteristically the mucoid secretion products of the epithelial tissues in lung, pancreas, liver and intestine have a high viscosity. The pathophysiology is characterized by obstruction of these organs with secondary damage and finally destruction. For a long period intestinal obstruction syndromes in CF were ascribed only to the pancreatic insufficiency. Malabsorption is not only caused by enzyme deficiency but is also related to transport processes to the surface of the enterocytes. This indicates that the intestinal disorders in CF are partly the result of mucoid plugging and not only of pancreatic insufficiency. Recently in vitro studies have shown a blockade of secretion through chloride channels in the mucosal membrane of CF tissues. In vivo measurements of chloride fluxes in the rectum showed a disturbed regulation in CF patients. The high viscosity of the mucus and plugging is directly related to the diminished chloride secretion. So it is postulated that the abnormal chloride secretion is responsible for the intestinal obstruction and partially also for the malabsorption."} {"id": "PMID:1281908", "title": "[Quantitative analysis of individual RNA in preparations of poly(A)+-RNA mammalian cells].", "content": "A new method of simultaneous analysis of the relative abundance of the most abundant individual mRNA's in poly(A)(+)-RNA preparations is described. The method is based on the synthesis of short (10-20 nucleotides) cDNA products by reverse transcription of poly(A)(+)-RNA primed with 5'-labeled oligonucleotides of 9 nucleotide lengths. Three natural nucleotides and one terminator nucleotide are used as substrates for reverse transcriptase. The numbers, lengths and sequence of the oligonucleotides used as primers were chosen to provide more than a 90% probability that synthesis would be initiated from any individual RNA present in the poly(A)(+)-RNA, thus assuring comprehensive analysis of RNA with abundance higher than 0.01%. Each primer produces about 20-60 bands per track following polyacrylamide electrophoresis under denaturing conditions. A full set of 30 oligonucleotides used to analyze a poly(A)(+)-RNA preparation produces an electrophoretic pattern with information capacity similar to that obtained from high resolution 2-dimensional electrophoresis of protein. Using this method we show that the patterns of poly(A)(+)-RNA differ from tissue to tissue, from normal tissues to neoplastic tissue (human myoma of uterus) and during differentiation of a F9 embryonic carcinoma cell line.", "contents": "[Quantitative analysis of individual RNA in preparations of poly(A)+-RNA mammalian cells]. A new method of simultaneous analysis of the relative abundance of the most abundant individual mRNA's in poly(A)(+)-RNA preparations is described. The method is based on the synthesis of short (10-20 nucleotides) cDNA products by reverse transcription of poly(A)(+)-RNA primed with 5'-labeled oligonucleotides of 9 nucleotide lengths. Three natural nucleotides and one terminator nucleotide are used as substrates for reverse transcriptase. The numbers, lengths and sequence of the oligonucleotides used as primers were chosen to provide more than a 90% probability that synthesis would be initiated from any individual RNA present in the poly(A)(+)-RNA, thus assuring comprehensive analysis of RNA with abundance higher than 0.01%. Each primer produces about 20-60 bands per track following polyacrylamide electrophoresis under denaturing conditions. A full set of 30 oligonucleotides used to analyze a poly(A)(+)-RNA preparation produces an electrophoretic pattern with information capacity similar to that obtained from high resolution 2-dimensional electrophoresis of protein. Using this method we show that the patterns of poly(A)(+)-RNA differ from tissue to tissue, from normal tissues to neoplastic tissue (human myoma of uterus) and during differentiation of a F9 embryonic carcinoma cell line."} {"id": "PMID:1281911", "title": "[Renal accumulation of radioiodinated alpha-1-microglobulin increases in the mononephrectomised rat].", "content": "Alpha-1-microglobulin (alpha 1M) is highly accumulated by the kidneys of normal rats. Aim of this study has been to verify if uninephrectomy can modify this behaviour. For this purpose the radioactivity of the remaining kidney and those of plasma and urine have been measured in uninephrectomized rats after IV injection of radioiodinated alpha 1M. The experiments have been performed in 100 Sprague-Dawley male rats. Fifty animals underwent right nephrectomy, the others being the controls. Uninephrectomized rats and their controls have been divided in 3 groups, studied 4, 14 and 28 days after surgery, respectively. All the animals were injected with human alpha 1M labelled with iodine-131. They were sacrificed in part 18 minutes after the injection of labelled alpha 1M (time of highest kidney accumulation in the normal rat), and in part 28 minutes after the injection. Uninephrectomy increased plasma retention of labelled alpha 1M. Kidney uptake (total and per gram) was always higher in uninephrectomized animals. Similarly, urine radioactivity was higher in uninephrectomized rats. These results demonstrate that uninephrectomy remarkably increases the accumulation of alpha 1M in the remaining kidney.", "contents": "[Renal accumulation of radioiodinated alpha-1-microglobulin increases in the mononephrectomised rat]. Alpha-1-microglobulin (alpha 1M) is highly accumulated by the kidneys of normal rats. Aim of this study has been to verify if uninephrectomy can modify this behaviour. For this purpose the radioactivity of the remaining kidney and those of plasma and urine have been measured in uninephrectomized rats after IV injection of radioiodinated alpha 1M. The experiments have been performed in 100 Sprague-Dawley male rats. Fifty animals underwent right nephrectomy, the others being the controls. Uninephrectomized rats and their controls have been divided in 3 groups, studied 4, 14 and 28 days after surgery, respectively. All the animals were injected with human alpha 1M labelled with iodine-131. They were sacrificed in part 18 minutes after the injection of labelled alpha 1M (time of highest kidney accumulation in the normal rat), and in part 28 minutes after the injection. Uninephrectomy increased plasma retention of labelled alpha 1M. Kidney uptake (total and per gram) was always higher in uninephrectomized animals. Similarly, urine radioactivity was higher in uninephrectomized rats. These results demonstrate that uninephrectomy remarkably increases the accumulation of alpha 1M in the remaining kidney."} {"id": "PMID:1281912", "title": "The capsaicin test in mice for evaluating tachykinin antagonists in the spinal cord.", "content": "A capsaicin test involving peripheral nociception, which produces behaviour similar to that elicited by formalin, is described in mice. Capsaicin was injected subcutaneously (s.c.) into the dorsal surface of a hindpaw and the time the animals spent licking the paw was recorded. Doses of capsaicin of 6.25-1600 ng induced nociception, during a period of 5 min, starting immediately after injection and disappearing completely at 10 min. Intrathecally (i.t.) administered [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), a tachykinin antagonist and [D-Phe7,D-His9]substance P (6-11), a selective antagonist of substance P (SP), inhibited the capsaicin-induced behaviour, in a dose-dependent manner. This licking behaviour was also inhibited by intrathecal administration of SP antiserum but not by somatostatin (SOM) antiserum. Intrathecal pretreatment with capsaicin resulted in a marked reduction of the licking response, following subcutaneous injection of capsaicin into the paw. Capsaicin-induced licking was not affected by intrathecal administration of cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr], a SOM antagonist and by intrathecal pretreatment with cysteamine, a SOM depletor. This nociceptive test may allow discrimination between SP- and SOM-mediated responses in the spinal cord of the mouse.", "contents": "The capsaicin test in mice for evaluating tachykinin antagonists in the spinal cord. A capsaicin test involving peripheral nociception, which produces behaviour similar to that elicited by formalin, is described in mice. Capsaicin was injected subcutaneously (s.c.) into the dorsal surface of a hindpaw and the time the animals spent licking the paw was recorded. Doses of capsaicin of 6.25-1600 ng induced nociception, during a period of 5 min, starting immediately after injection and disappearing completely at 10 min. Intrathecally (i.t.) administered [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), a tachykinin antagonist and [D-Phe7,D-His9]substance P (6-11), a selective antagonist of substance P (SP), inhibited the capsaicin-induced behaviour, in a dose-dependent manner. This licking behaviour was also inhibited by intrathecal administration of SP antiserum but not by somatostatin (SOM) antiserum. Intrathecal pretreatment with capsaicin resulted in a marked reduction of the licking response, following subcutaneous injection of capsaicin into the paw. Capsaicin-induced licking was not affected by intrathecal administration of cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr], a SOM antagonist and by intrathecal pretreatment with cysteamine, a SOM depletor. This nociceptive test may allow discrimination between SP- and SOM-mediated responses in the spinal cord of the mouse."} {"id": "PMID:1281913", "title": "The neuropeptide galanin occurs in two conformations.", "content": "The secondary structure of the six known species forms of galanin was predicted using a statistical method. In the region between positions 13 and 20 the model predicts alpha-helical structures in human, cow, and chicken galanin, whereas the model does not predict alpha-helical structures in the same region of pig, rat, and sheep galanin. Based on the different conformational states of galanin, the species forms of galanin could be divided in two groups: galanin A (= human, cow, chicken galanin) and galanin B (= pig, rat, and sheep galanin). A chemical explanation might thus be provided for the observed differences in potency between different species forms of galanin (A or B) to inhibit insulin secretion.", "contents": "The neuropeptide galanin occurs in two conformations. The secondary structure of the six known species forms of galanin was predicted using a statistical method. In the region between positions 13 and 20 the model predicts alpha-helical structures in human, cow, and chicken galanin, whereas the model does not predict alpha-helical structures in the same region of pig, rat, and sheep galanin. Based on the different conformational states of galanin, the species forms of galanin could be divided in two groups: galanin A (= human, cow, chicken galanin) and galanin B (= pig, rat, and sheep galanin). A chemical explanation might thus be provided for the observed differences in potency between different species forms of galanin (A or B) to inhibit insulin secretion."} {"id": "PMID:1281914", "title": "Release and depletion of substance P by capsaicin in substantia gelatinosa studied with the antibody microprobe technique and immunohistochemistry.", "content": "Using an antibody microprobe technique, we have detected substance P release from the region of the substantia gelatinosa of the cat during the first, but not the second, 30 min of topical application of capsaicin (1-3%) to the tibial nerve. Immunohistochemical analysis also showed that substance P-like immunoreactivity was markedly reduced in the superficial layer of the dorsal horn 30 min after application of capsaicin. These results indicate that substance P is released and then depleted from primary afferent central terminals following acute application of capsaicin to the peripheral sensory nerve.", "contents": "Release and depletion of substance P by capsaicin in substantia gelatinosa studied with the antibody microprobe technique and immunohistochemistry. Using an antibody microprobe technique, we have detected substance P release from the region of the substantia gelatinosa of the cat during the first, but not the second, 30 min of topical application of capsaicin (1-3%) to the tibial nerve. Immunohistochemical analysis also showed that substance P-like immunoreactivity was markedly reduced in the superficial layer of the dorsal horn 30 min after application of capsaicin. These results indicate that substance P is released and then depleted from primary afferent central terminals following acute application of capsaicin to the peripheral sensory nerve."} {"id": "PMID:1281915", "title": "Magnetic resonance imaging and pathological correlates of meningiomas.", "content": "We examined the relationships between specific magnetic resonance imaging features and certain gross and microscopic characteristics of meningiomas, including vascularity, gross texture (consistency), and venous sinus involvement. Magnetic resonance imaging scans, surgery reports, and the histopathological findings of tumors were examined retrospectively in 54 patients. Sinus involvement was accurately predicted on T1-weighted images in 9 of 10 cases (P = 0.001) and tumors with cystic changes in 3 of 3 cases. T1-weighted images were not useful for predicting vascularity unless actual flow voids could be visualized (five of six cases). There was no correlation between T1 signal intensity, tumor consistency, or histological findings. In tumors without detectable vascularity on T1-weighted images, hyperintensity relative to gray matter on T2-weighted images was correlated with increased vascularity (P = 0.004). Tumors with soft consistency (P = 0.007), cellular atypia, invasion, angioblastic, or melanocytic components were also hyperintense, compared with gray matter on T2-weighted images (P = 0.0266). Aggressive meningiomas were found to be more vascular (P = 0.045). No correlation was found between the degree of surrounding edema or contrast enhancement with histopathological findings, vascularity, or consistency.", "contents": "Magnetic resonance imaging and pathological correlates of meningiomas. We examined the relationships between specific magnetic resonance imaging features and certain gross and microscopic characteristics of meningiomas, including vascularity, gross texture (consistency), and venous sinus involvement. Magnetic resonance imaging scans, surgery reports, and the histopathological findings of tumors were examined retrospectively in 54 patients. Sinus involvement was accurately predicted on T1-weighted images in 9 of 10 cases (P = 0.001) and tumors with cystic changes in 3 of 3 cases. T1-weighted images were not useful for predicting vascularity unless actual flow voids could be visualized (five of six cases). There was no correlation between T1 signal intensity, tumor consistency, or histological findings. In tumors without detectable vascularity on T1-weighted images, hyperintensity relative to gray matter on T2-weighted images was correlated with increased vascularity (P = 0.004). Tumors with soft consistency (P = 0.007), cellular atypia, invasion, angioblastic, or melanocytic components were also hyperintense, compared with gray matter on T2-weighted images (P = 0.0266). Aggressive meningiomas were found to be more vascular (P = 0.045). No correlation was found between the degree of surrounding edema or contrast enhancement with histopathological findings, vascularity, or consistency."} {"id": "PMID:1281916", "title": "Antihistamines and decongestants.", "content": "Drug therapy for allergic rhinitis is used either to prevent symptoms from occurring by short-circuiting the reaction and thus inhibiting the production of chemical mediators or to control symptoms after the target organs have been stimulated by these mediators. Antihistamines, the mainstay treatment of allergic rhinitis, are H1-receptor antagonists that bind competitively to histamine receptors. The older, classic antihistamines are effective in treating the symptoms of allergic rhinitis, but most are sedating because they cross the blood-brain barrier. They also have anticholinergic activity, which further restricts their use. The new, nonsedating antihistamines have overcome most of these limitations, and because they are long-acting, they require fewer daily dosages. Many still under development are quite potent and may be used for indications other than allergic rhinitis. Decongestants, sympathomimetic amines, are available both orally and topically as either short- or long-acting preparations. Topical decongestants should be used only for a short time to prevent rebound and ensuring overusage. These drugs interact with numerous antihypertensive medications and tricyclic antidepressants. Often combined with antihistamines, decongestants help offset their sedative effect.", "contents": "Antihistamines and decongestants. Drug therapy for allergic rhinitis is used either to prevent symptoms from occurring by short-circuiting the reaction and thus inhibiting the production of chemical mediators or to control symptoms after the target organs have been stimulated by these mediators. Antihistamines, the mainstay treatment of allergic rhinitis, are H1-receptor antagonists that bind competitively to histamine receptors. The older, classic antihistamines are effective in treating the symptoms of allergic rhinitis, but most are sedating because they cross the blood-brain barrier. They also have anticholinergic activity, which further restricts their use. The new, nonsedating antihistamines have overcome most of these limitations, and because they are long-acting, they require fewer daily dosages. Many still under development are quite potent and may be used for indications other than allergic rhinitis. Decongestants, sympathomimetic amines, are available both orally and topically as either short- or long-acting preparations. Topical decongestants should be used only for a short time to prevent rebound and ensuring overusage. These drugs interact with numerous antihypertensive medications and tricyclic antidepressants. Often combined with antihistamines, decongestants help offset their sedative effect."} {"id": "PMID:1281917", "title": "Rhinitis during pregnancy and rhinitis medicamentosa.", "content": "Vasomotor rhinitis is a nonspecific disorder that is caused neither by infection nor allergy but rather by an imbalance of the autonomic nervous system with a preponderant action of parasympathetic fibers on nasal blood vessels. Rhinitis during pregnancy appears to result from the increased production of estrogen; increased estrogen levels caused by treatment, puberty, or liver disease may also cause rhinitis. Nasal saline mist, antihistamines, and topical corticosteroids are recommended; intranasal corticosteroid injections are also useful but must be administered under expert care. Rhinitis medicamentosa results from overuse of topical vasoconstrictors, which produce a rebound phenomenon. Rebound can also result from numerous medications, including antihypertensive preparations that reduce catecholamine levels, antidepressants, antipsychotics, and tranquilizers. Management of rhinitis medicamentosa consists in limiting the use of vasoconstrictors to no more than 3 days and giving the patient saline nasal sprays, daytime oral vasoconstrictors, and nocturnal antihistamines. Corticosteroids, preferably topical nasal steroids rather than even a short-term course of systemic administration, should also be used.", "contents": "Rhinitis during pregnancy and rhinitis medicamentosa. Vasomotor rhinitis is a nonspecific disorder that is caused neither by infection nor allergy but rather by an imbalance of the autonomic nervous system with a preponderant action of parasympathetic fibers on nasal blood vessels. Rhinitis during pregnancy appears to result from the increased production of estrogen; increased estrogen levels caused by treatment, puberty, or liver disease may also cause rhinitis. Nasal saline mist, antihistamines, and topical corticosteroids are recommended; intranasal corticosteroid injections are also useful but must be administered under expert care. Rhinitis medicamentosa results from overuse of topical vasoconstrictors, which produce a rebound phenomenon. Rebound can also result from numerous medications, including antihypertensive preparations that reduce catecholamine levels, antidepressants, antipsychotics, and tranquilizers. Management of rhinitis medicamentosa consists in limiting the use of vasoconstrictors to no more than 3 days and giving the patient saline nasal sprays, daytime oral vasoconstrictors, and nocturnal antihistamines. Corticosteroids, preferably topical nasal steroids rather than even a short-term course of systemic administration, should also be used."} {"id": "PMID:1281918", "title": "Characterization of monoclonal antibodies against eosinophil chemotactic factors from young adult worms of Angiostrongylus cantonensis.", "content": "Two kinds of IgG1 monoclonal antibodies against eosinophil chemotactic factors (ECFs) derived from Angiostrongylus cantonensis young adult worms (YA) were established. Western blot analyses demonstrated that one monoclonal antibody recognized a 16.1 kD component of YA-whole worm extract, and the other an 85 kD component. These antibodies did not show any cross reactions against several helminth antigens, as assessed by ELISA. The chemotactic activity of YA-whole worm extract for guinea-pig-eosinophils was significantly inhibited by previous incubation of the extract with these monoclonal antibodies; the monoclonal antibody recognizing the 16.1 kD component inhibited 56-61% of the ECF activity whilst the antibody recognizing the 85 kD component inhibited 20-34% of the activity. The combination of both monoclonal antibodies showed a stronger inhibitory effect (71-81%) than either antibody alone. Similar magnitudes of inhibition were noted when the chemotactic activity for human eosinophils was measured using YA-whole worm extract preincubated with these monoclonal antibodies. Neither monoclonal antibodies inhibited the chemotactic activity of whole worm extracts of A. cantonensis first stage larvae, Metastrongylus apri adult worms, Spirometra erinacei plerocercoids and Fasciola sp. adult worms. These data suggest that the two monoclonal antibodies will be useful for the isolation and purification of ECF-YA as well as for elucidating the possible in vivo role of ECF-YA.", "contents": "Characterization of monoclonal antibodies against eosinophil chemotactic factors from young adult worms of Angiostrongylus cantonensis. Two kinds of IgG1 monoclonal antibodies against eosinophil chemotactic factors (ECFs) derived from Angiostrongylus cantonensis young adult worms (YA) were established. Western blot analyses demonstrated that one monoclonal antibody recognized a 16.1 kD component of YA-whole worm extract, and the other an 85 kD component. These antibodies did not show any cross reactions against several helminth antigens, as assessed by ELISA. The chemotactic activity of YA-whole worm extract for guinea-pig-eosinophils was significantly inhibited by previous incubation of the extract with these monoclonal antibodies; the monoclonal antibody recognizing the 16.1 kD component inhibited 56-61% of the ECF activity whilst the antibody recognizing the 85 kD component inhibited 20-34% of the activity. The combination of both monoclonal antibodies showed a stronger inhibitory effect (71-81%) than either antibody alone. Similar magnitudes of inhibition were noted when the chemotactic activity for human eosinophils was measured using YA-whole worm extract preincubated with these monoclonal antibodies. Neither monoclonal antibodies inhibited the chemotactic activity of whole worm extracts of A. cantonensis first stage larvae, Metastrongylus apri adult worms, Spirometra erinacei plerocercoids and Fasciola sp. adult worms. These data suggest that the two monoclonal antibodies will be useful for the isolation and purification of ECF-YA as well as for elucidating the possible in vivo role of ECF-YA."} {"id": "PMID:1281919", "title": "Prony-Householder method applied to 31P NMR signals: II. Study of conjugates of ara-AMP with lactosaminated albumin.", "content": "Conjugates of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin (L-SA), obtained by using two different coupling procedures, produce antibodies in rats and mice which display only a small cross-reactivity. 31P NMR signals from the two conjugates have been examined to clarify whether different lysine and histidine residues are involved in the two reaction pathways. The occurrence of different chemical shifts and linewidths between the two conjugates, as evidenced by processing the signals with the Prony-Householder method, indicates the formation of two different complexes.", "contents": "Prony-Householder method applied to 31P NMR signals: II. Study of conjugates of ara-AMP with lactosaminated albumin. Conjugates of 9-beta-D-arabinofuranosyladenine 5'-monophosphate (ara-AMP) with lactosaminated albumin (L-SA), obtained by using two different coupling procedures, produce antibodies in rats and mice which display only a small cross-reactivity. 31P NMR signals from the two conjugates have been examined to clarify whether different lysine and histidine residues are involved in the two reaction pathways. The occurrence of different chemical shifts and linewidths between the two conjugates, as evidenced by processing the signals with the Prony-Householder method, indicates the formation of two different complexes."} {"id": "PMID:1281920", "title": "Peptide 204-212 of lipocortin 5 inhibits the generation of a prostacyclin-like factor from rat aorta preparations in vitro.", "content": "The release of an endogenous prostacyclin-like factor (PLF) from rat thoracic aorta rings was evaluated through inhibition of platelet ADP-induced aggregation and assessed with a micro-method using 96-multiwell plates. Aggregation was assessed in an ELISA reader by measuring changes of optical density at 620 nm in each well. The generation of endogenous PLF by aortic rings was time-dependent and was inhibited by indomethacin (3 microM). ADP-induced aggregation was inhibited by iloprost in a dose-dependent manner. Incubation of rat aorta rings with peptide 204-212 of human lipocortin 5 (1-100 micrograms/ml) resulted in a dose-dependent inhibition of PLF release with a maximal inhibition of 90-95%. The effect of peptide 204-212 was reversible. A control peptide (amino-acids 104-112 of lipocortin 5) was without any significant effect. Peptide 204-212 (100 micrograms/ml) did not modify PLF release from rat aorta preparations challenged with arachidonic acid (10(-6)-10(-4) M).", "contents": "Peptide 204-212 of lipocortin 5 inhibits the generation of a prostacyclin-like factor from rat aorta preparations in vitro. The release of an endogenous prostacyclin-like factor (PLF) from rat thoracic aorta rings was evaluated through inhibition of platelet ADP-induced aggregation and assessed with a micro-method using 96-multiwell plates. Aggregation was assessed in an ELISA reader by measuring changes of optical density at 620 nm in each well. The generation of endogenous PLF by aortic rings was time-dependent and was inhibited by indomethacin (3 microM). ADP-induced aggregation was inhibited by iloprost in a dose-dependent manner. Incubation of rat aorta rings with peptide 204-212 of human lipocortin 5 (1-100 micrograms/ml) resulted in a dose-dependent inhibition of PLF release with a maximal inhibition of 90-95%. The effect of peptide 204-212 was reversible. A control peptide (amino-acids 104-112 of lipocortin 5) was without any significant effect. Peptide 204-212 (100 micrograms/ml) did not modify PLF release from rat aorta preparations challenged with arachidonic acid (10(-6)-10(-4) M)."} {"id": "PMID:1281921", "title": "Pharmacokinetics of iloprost and cicaprost in mice.", "content": "Iloprost and cicaprost are two PGI2-mimetics, which are chemically stable and highly pharmacologically potent. Both compounds differ by their susceptibility to metabolic degradation. While iloprost contains a pentanoic acid upper side chain, which is subject to beta-oxidative degradation, cicaprost is metabolically stabilized by the introduction of an oxygen atom at position 3 of the pentanoic acid chain, preventing beta-oxidation. Both compounds have been characterized concerning their pharmacological and pharmacokinetic profile in a number of animal species and in man. In the present set of experiments both drugs were characterized in terms of pharmacokinetics in mice, an animal species quite routinely used in long-term toxicity studies on cancerogenicity, by iv and ig administration of 0.2 mg/kg (iloprost) and 0.01 mg/kg (cicaprost) using tritiated substances. Iloprost was rapidly inactivated after iv dosing with plasma levels declining from 247 to 0.27 ng/ml within 60 min. Disposition half-lives were 3 and 14 min. Total clerance accounted for 152 ml/min/kg. Total radiolabel exhibited a clearance of 35 ml/min/kg, its AUC in plasma was 146 ng-equiv.h/ml. After ig administration Iloprost peak plasma levels of 9.2 ng/ml occurred after 5 min. Bioavailability was 10%. AUC of total radiolabel was 152 ng-equiv.h/ml, showing complete absorption. Excretion of 3H-label was 41%/57% of dose (iv) and 36%/47% o.d. (ig) with the urine and 32%/18% o.d. (iv) and 36%/25% o.d. (ig) in male/female animals and proceeded for > 90% of dose fraction recovered with half-lives of 0.2-0.3 d. Metabolic patterns revealed the known profile consisting of unchanged drug, dinor- and tetranor-metabolites in plasma and mainly, tetranor-products in urine and feces. After iv dosing of cicaprost total radiolabel plasma levels declined biphasically with half-lives of approx. 0.05 h and 0.31 h. Extrapolated AUC was 1.6 ng-equiv. h/ml and total clearance accounted for 108 ml/min/kg. After ig treatment peak radioactivity plasma levels of 0.7 and 1 ng-equiv./ml were observed at 0.16 and 1 h postdose, probably due to differences between animal groups. Extrapolated AUC was 1 ng-equiv.h/ml. Excretion of 3H-label was mainly biliary: With the feces 83%/89% o.d. (iv) and 93%/92% o.d. (ig) were excreted by male/female animals, while 8.3%/5.7% o.d. (iv) and 2.6%/5.5% were recovered in the urine. More than 90% of the excreted radiolabel was found in samples collected up to 24 h postdose. Metabolic patterns in plasma revealed that after both routes of administration 3H-cicaprost was the dominant radiolabel fraction accounting for up to 90% of total radiolabel chromatographed.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Pharmacokinetics of iloprost and cicaprost in mice. Iloprost and cicaprost are two PGI2-mimetics, which are chemically stable and highly pharmacologically potent. Both compounds differ by their susceptibility to metabolic degradation. While iloprost contains a pentanoic acid upper side chain, which is subject to beta-oxidative degradation, cicaprost is metabolically stabilized by the introduction of an oxygen atom at position 3 of the pentanoic acid chain, preventing beta-oxidation. Both compounds have been characterized concerning their pharmacological and pharmacokinetic profile in a number of animal species and in man. In the present set of experiments both drugs were characterized in terms of pharmacokinetics in mice, an animal species quite routinely used in long-term toxicity studies on cancerogenicity, by iv and ig administration of 0.2 mg/kg (iloprost) and 0.01 mg/kg (cicaprost) using tritiated substances. Iloprost was rapidly inactivated after iv dosing with plasma levels declining from 247 to 0.27 ng/ml within 60 min. Disposition half-lives were 3 and 14 min. Total clerance accounted for 152 ml/min/kg. Total radiolabel exhibited a clearance of 35 ml/min/kg, its AUC in plasma was 146 ng-equiv.h/ml. After ig administration Iloprost peak plasma levels of 9.2 ng/ml occurred after 5 min. Bioavailability was 10%. AUC of total radiolabel was 152 ng-equiv.h/ml, showing complete absorption. Excretion of 3H-label was 41%/57% of dose (iv) and 36%/47% o.d. (ig) with the urine and 32%/18% o.d. (iv) and 36%/25% o.d. (ig) in male/female animals and proceeded for > 90% of dose fraction recovered with half-lives of 0.2-0.3 d. Metabolic patterns revealed the known profile consisting of unchanged drug, dinor- and tetranor-metabolites in plasma and mainly, tetranor-products in urine and feces. After iv dosing of cicaprost total radiolabel plasma levels declined biphasically with half-lives of approx. 0.05 h and 0.31 h. Extrapolated AUC was 1.6 ng-equiv. h/ml and total clearance accounted for 108 ml/min/kg. After ig treatment peak radioactivity plasma levels of 0.7 and 1 ng-equiv./ml were observed at 0.16 and 1 h postdose, probably due to differences between animal groups. Extrapolated AUC was 1 ng-equiv.h/ml. Excretion of 3H-label was mainly biliary: With the feces 83%/89% o.d. (iv) and 93%/92% o.d. (ig) were excreted by male/female animals, while 8.3%/5.7% o.d. (iv) and 2.6%/5.5% were recovered in the urine. More than 90% of the excreted radiolabel was found in samples collected up to 24 h postdose. Metabolic patterns in plasma revealed that after both routes of administration 3H-cicaprost was the dominant radiolabel fraction accounting for up to 90% of total radiolabel chromatographed.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281922", "title": "[Drug-induced pulmonary diseases: diagnostic, therapeutic and prognostic aspects. Apropos of 10 personal case reports].", "content": "The authors report ten cases of drug induced lung diseases, complicated by respiratory failure of whom five were attributed to cytotoxic drugs and five to non cytotoxic drugs. The drug induced lung disease presented as acute respiratory distress syndrome in two cases, alveolar interstitial lung disease in three cases, purely interstitial in five cases. There was acute respiratory failure (ARF) in eight cases and chronic respiratory failure (CRF) in two cases. Among the five patients admitted for cytotoxic drug induced lung disease and ARF, four recovered and one died of diffuse destructive pulmonary fibrosis. Among the five patients having non cytotoxic drug induced lung disease, three were in ARF and recovered. The other two had CRF and died of diffuse pulmonary fibrosis. The diagnostic of drug induced lung disease was established in each case with the chronology of the clinical events, the exclusion of other possible causes of the lung disease and the evolution after removal of the incriminated drug. Broncho-alveolar lavage (BAL) had a major diagnostic value. It was contraindicated by respiratory failure in five cases. The predominant alveolar cell type was lymphocyte (four cases), eosinophil (three cases) and neutrophil (one case), BAL was realized with a provocation test and demonstrated the pathogenic role of cyclothiazide in one case. No specific information was given by histology. The prognosis did not seem to be linked to the severity of the initial clinical picture, or to the nature of the underlying neoplastic disorder, but to the degree and evolution of the pulmonary fibrosis.", "contents": "[Drug-induced pulmonary diseases: diagnostic, therapeutic and prognostic aspects. Apropos of 10 personal case reports]. The authors report ten cases of drug induced lung diseases, complicated by respiratory failure of whom five were attributed to cytotoxic drugs and five to non cytotoxic drugs. The drug induced lung disease presented as acute respiratory distress syndrome in two cases, alveolar interstitial lung disease in three cases, purely interstitial in five cases. There was acute respiratory failure (ARF) in eight cases and chronic respiratory failure (CRF) in two cases. Among the five patients admitted for cytotoxic drug induced lung disease and ARF, four recovered and one died of diffuse destructive pulmonary fibrosis. Among the five patients having non cytotoxic drug induced lung disease, three were in ARF and recovered. The other two had CRF and died of diffuse pulmonary fibrosis. The diagnostic of drug induced lung disease was established in each case with the chronology of the clinical events, the exclusion of other possible causes of the lung disease and the evolution after removal of the incriminated drug. Broncho-alveolar lavage (BAL) had a major diagnostic value. It was contraindicated by respiratory failure in five cases. The predominant alveolar cell type was lymphocyte (four cases), eosinophil (three cases) and neutrophil (one case), BAL was realized with a provocation test and demonstrated the pathogenic role of cyclothiazide in one case. No specific information was given by histology. The prognosis did not seem to be linked to the severity of the initial clinical picture, or to the nature of the underlying neoplastic disorder, but to the degree and evolution of the pulmonary fibrosis."} {"id": "PMID:1281923", "title": "A review of the morphology of human nasal mast cells as studied by light and electron microscopy.", "content": "This review discusses the distribution and classification of human nasal mast cells after the use of different fixatives, and some of their staining characteristics, both at the light- and electron-microscopical level. The problems encountered with alcoholic and formaldehyde fixation are discussed as well as the limitations of different stains (including the basic aniline dyes), esterase cytochemistry and immunological techniques. Also, the respective limitations of light and electron microscopy are compared. Cells studied by means of electron microscopy are much more difficult to quantify objectively. It is concluded that classification of mast cells--by means of their morphology, fixation and staining characteristics--into two categories (mucosal vs. connective tissue; T-vs. T/C cells) is simplistic, especially since human nasal mast cells are both heterogeneous and pleomorphic.", "contents": "A review of the morphology of human nasal mast cells as studied by light and electron microscopy. This review discusses the distribution and classification of human nasal mast cells after the use of different fixatives, and some of their staining characteristics, both at the light- and electron-microscopical level. The problems encountered with alcoholic and formaldehyde fixation are discussed as well as the limitations of different stains (including the basic aniline dyes), esterase cytochemistry and immunological techniques. Also, the respective limitations of light and electron microscopy are compared. Cells studied by means of electron microscopy are much more difficult to quantify objectively. It is concluded that classification of mast cells--by means of their morphology, fixation and staining characteristics--into two categories (mucosal vs. connective tissue; T-vs. T/C cells) is simplistic, especially since human nasal mast cells are both heterogeneous and pleomorphic."} {"id": "PMID:1281924", "title": "Nasal airflow asymmetry and the effects of a topical nasal decongestant.", "content": "Nasal airway resistance (NAR) is normally asymmetrical due to the nasal cycle. The aims of this study were to determine the degree of this asymmetry in healthy subjects and those with acute rhinitis associated with common cold, and to investigate how the administration of a topical nasal decongestant (xylometazoline) influenced the asymmetry in NAR. Unilateral NAR was measured by active anterior rhinomanometry, and was shown to be asymmetrical in both healthy subjects and those suffering with acute rhinitis. The asymmetry in NAR was greater in those with acute rhinitis than in the healthy group, with a ratio between \"high\" and \"low\" sides of 2.3:1 in the rhinitis group compared to a ratio of 1.7:1 in the healthy subjects. Administration of a topical nasal decongestant caused a significant decrease in total NAR in both groups and abolished the asymmetry in NAR in the healthy subjects (ratio is 1:1 after decongestion). However, significant asymmetry of NAR was still present in the group with acute rhinitis following the administration of decongestant (ratio is 1.5:1 after decongestion). These findings show that the normal asymmetry in NAR was increased during acute rhinitis associated with common cold, and that in healthy subjects (but not in those with rhinitis) the asymmetry was abolished by administration of a topical decongestant. The results are discussed in relation to nasal sympathetic tone and nasal blood flow.", "contents": "Nasal airflow asymmetry and the effects of a topical nasal decongestant. Nasal airway resistance (NAR) is normally asymmetrical due to the nasal cycle. The aims of this study were to determine the degree of this asymmetry in healthy subjects and those with acute rhinitis associated with common cold, and to investigate how the administration of a topical nasal decongestant (xylometazoline) influenced the asymmetry in NAR. Unilateral NAR was measured by active anterior rhinomanometry, and was shown to be asymmetrical in both healthy subjects and those suffering with acute rhinitis. The asymmetry in NAR was greater in those with acute rhinitis than in the healthy group, with a ratio between \"high\" and \"low\" sides of 2.3:1 in the rhinitis group compared to a ratio of 1.7:1 in the healthy subjects. Administration of a topical nasal decongestant caused a significant decrease in total NAR in both groups and abolished the asymmetry in NAR in the healthy subjects (ratio is 1:1 after decongestion). However, significant asymmetry of NAR was still present in the group with acute rhinitis following the administration of decongestant (ratio is 1.5:1 after decongestion). These findings show that the normal asymmetry in NAR was increased during acute rhinitis associated with common cold, and that in healthy subjects (but not in those with rhinitis) the asymmetry was abolished by administration of a topical decongestant. The results are discussed in relation to nasal sympathetic tone and nasal blood flow."} {"id": "PMID:1281925", "title": "Immunological cross-reaction between an Onchocerca paramyosin-like molecule and a microfilaria surface antigen.", "content": "A monoclonal antibody (2A5B9), previously shown to be reactive with a 14 kD surface associated antigen of Onchocerca microfilariae, was found to recognise a 92 kD molecule present in an adult worm extract. The antibody was used to select cDNA clones with a coding capacity larger than 14 kD, from a lambda gt11 library of O. volvulus. Nucleotide sequencing of the cDNA of one such clone revealed extensive homology to the myosin (unc-54) and paramyosin (unc-15) genes of Caenorhabditis elegans, similarly to myosin and paramyosin genes of Onchocerca volvulus, Brugia malayi, Dirofilaria immitis and Schistosoma mansoni. The immunological implications of antigenic cross-reactivity between a surface molecule and paramyosin, a known protective antigen, are discussed.", "contents": "Immunological cross-reaction between an Onchocerca paramyosin-like molecule and a microfilaria surface antigen. A monoclonal antibody (2A5B9), previously shown to be reactive with a 14 kD surface associated antigen of Onchocerca microfilariae, was found to recognise a 92 kD molecule present in an adult worm extract. The antibody was used to select cDNA clones with a coding capacity larger than 14 kD, from a lambda gt11 library of O. volvulus. Nucleotide sequencing of the cDNA of one such clone revealed extensive homology to the myosin (unc-54) and paramyosin (unc-15) genes of Caenorhabditis elegans, similarly to myosin and paramyosin genes of Onchocerca volvulus, Brugia malayi, Dirofilaria immitis and Schistosoma mansoni. The immunological implications of antigenic cross-reactivity between a surface molecule and paramyosin, a known protective antigen, are discussed."} {"id": "PMID:1281926", "title": "Specific and sensitive IgG4 immunodiagnosis of onchocerciasis with a recombinant 33 kD Onchocerca volvulus protein (Ov33).", "content": "The full length cDNA of the immunodominant Ov33 protein of Onchocerca volvulus was expressed in E. coli using various vector constructs. Expression was best with the vectors pGEX2T and pCG808fx, yielding fusion protein Ov33-GST and Ov33-MBP, respectively. Purified fusion protein Ov33-GST and O. volvulus antigen extracts (OvAg) were used to compare antibody responses (IgM and IgG-subclasses) of patients infected with O. volvulus, Brugia malayi, Wuchereria bancrofti, Mansonella perstans/Loa loa and of Sudanese control sera. Sera of all groups contained IgM reacting with Ov33-GST and with OvAg. There was no IgG1 response to Ov33-GST. IgG1 responses to OvAg were only detected in filariasis sera. IgG2 and IgG3 responses were not detectable or marginal in all groups. The IgG4 reaction of onchocerciasis patients to Ov33-GST and to OvAg was high, whereas few other filariasis sera contained IgG4 antibodies to Ov33-GST and to OvAg. A serodiagnostic test for onchocerciasis based on detection of IgG4 to Ov33-GST had a sensitivity of 93.3% and a specificity of 96%. An epitope common to Ov33 and to the homologous proteins of other filarial species was demonstrated with a monoclonal antibody. Purified Ov33-MBP fusion protein was used to follow the development of the antibody response of four chimpanzees experimentally infected with O. volvulus. The data indicates that antibodies to Ov33 are induced by developing worms and later parasite stages.", "contents": "Specific and sensitive IgG4 immunodiagnosis of onchocerciasis with a recombinant 33 kD Onchocerca volvulus protein (Ov33). The full length cDNA of the immunodominant Ov33 protein of Onchocerca volvulus was expressed in E. coli using various vector constructs. Expression was best with the vectors pGEX2T and pCG808fx, yielding fusion protein Ov33-GST and Ov33-MBP, respectively. Purified fusion protein Ov33-GST and O. volvulus antigen extracts (OvAg) were used to compare antibody responses (IgM and IgG-subclasses) of patients infected with O. volvulus, Brugia malayi, Wuchereria bancrofti, Mansonella perstans/Loa loa and of Sudanese control sera. Sera of all groups contained IgM reacting with Ov33-GST and with OvAg. There was no IgG1 response to Ov33-GST. IgG1 responses to OvAg were only detected in filariasis sera. IgG2 and IgG3 responses were not detectable or marginal in all groups. The IgG4 reaction of onchocerciasis patients to Ov33-GST and to OvAg was high, whereas few other filariasis sera contained IgG4 antibodies to Ov33-GST and to OvAg. A serodiagnostic test for onchocerciasis based on detection of IgG4 to Ov33-GST had a sensitivity of 93.3% and a specificity of 96%. An epitope common to Ov33 and to the homologous proteins of other filarial species was demonstrated with a monoclonal antibody. Purified Ov33-MBP fusion protein was used to follow the development of the antibody response of four chimpanzees experimentally infected with O. volvulus. The data indicates that antibodies to Ov33 are induced by developing worms and later parasite stages."} {"id": "PMID:1281927", "title": "Identification of a lectin activity in Pneumocystis carinii.", "content": "Pneumocystitis carinii is known to adhere to pulmonary alveolar epithelial cells in vivo and to epithelial cell lines in vitro by a mechanism unknown at the molecular level. P. carinii is now found to adhere to rabbit and human red blood cells leading to rosette formation and hemagglutination. P. carinii erythrocyte-adherence was best inhibited by bovine submaxillary mucin and by a polysaccharide from the wall of group A Streptococcus, and to a lesser extent by Streptococcus group C polysaccharide, asialofetuin and fetuin. Among the mono- and oligosaccharides tested, only lactose inhibited hemagglutination. Other glycoconjugates and oligosaccharides tested were inactive. P. carinii also bound to purified glycoproteins coupled to Sepharose or adsorbed to plastic, and the binding was inhibited by soluble bovine submaxillary mucin. These results indicate that P. carinii has a novel surface lectin that may be important in adherence to lung alveolar epithelial cells.", "contents": "Identification of a lectin activity in Pneumocystis carinii. Pneumocystitis carinii is known to adhere to pulmonary alveolar epithelial cells in vivo and to epithelial cell lines in vitro by a mechanism unknown at the molecular level. P. carinii is now found to adhere to rabbit and human red blood cells leading to rosette formation and hemagglutination. P. carinii erythrocyte-adherence was best inhibited by bovine submaxillary mucin and by a polysaccharide from the wall of group A Streptococcus, and to a lesser extent by Streptococcus group C polysaccharide, asialofetuin and fetuin. Among the mono- and oligosaccharides tested, only lactose inhibited hemagglutination. Other glycoconjugates and oligosaccharides tested were inactive. P. carinii also bound to purified glycoproteins coupled to Sepharose or adsorbed to plastic, and the binding was inhibited by soluble bovine submaxillary mucin. These results indicate that P. carinii has a novel surface lectin that may be important in adherence to lung alveolar epithelial cells."} {"id": "PMID:1281928", "title": "Biochemistry of nitric oxide and its redox-activated forms.", "content": "Nitric oxide (NO.), a potentially toxic molecule, has been implicated in a wide range of biological functions. Details of its biochemistry, however, remain poorly understood. The broader chemistry of nitrogen monoxide (NO) involves a redox array of species with distinctive properties and reactivities: NO+ (nitrosonium), NO., and NO- (nitroxyl anion). The integration of this chemistry with current perspectives of NO biology illuminates many aspects of NO biochemistry, including the enzymatic mechanism of synthesis, the mode of transport and targeting in biological systems, the means by which its toxicity is mitigated, and the function-regulating interaction with target proteins.", "contents": "Biochemistry of nitric oxide and its redox-activated forms. Nitric oxide (NO.), a potentially toxic molecule, has been implicated in a wide range of biological functions. Details of its biochemistry, however, remain poorly understood. The broader chemistry of nitrogen monoxide (NO) involves a redox array of species with distinctive properties and reactivities: NO+ (nitrosonium), NO., and NO- (nitroxyl anion). The integration of this chemistry with current perspectives of NO biology illuminates many aspects of NO biochemistry, including the enzymatic mechanism of synthesis, the mode of transport and targeting in biological systems, the means by which its toxicity is mitigated, and the function-regulating interaction with target proteins."} {"id": "PMID:1281929", "title": "The treatment of chronic extremity pain in failed lumbar surgery. The role of lumbar sympathectomy.", "content": "Persistent lower extremity pain after unsuccessful lumbar surgery continues to be a disabling condition. The results of deafferentation procedures for radiculopathy have been disappointing. Hence, the prospect of isolating a potentially reversible component of extremity pain is quite attractive. Given the frequency with which vasomotor complaints occur in this setting, the occurrence of autonomic dysfunction seems quite plausible. Autonomic dysfunction was investigated in 17 patients who had undergone previous lumbar surgery and had chronic limb pain. Patients underwent a preblockade thermogram, sympathetic blockade, and postblockade thermograms. All patients reported substantial relief after blockade, and all underwent retroperitoneal sympathectomy. All patients were followed for at least 2 years. The clinical results were disappointing, with only one patient reporting substantial relief. Although the results of thermography initially seemed to correlate with clinical outcome, further follow-up failed to yield any correlation. Additionally, no specific combination of response to blockade or thermogram was predictive of the clinical success after sympathectomy. Now, lumbar sympathectomy is not recommended in the setting of chronic radiculopathy and persistent extremity pain.", "contents": "The treatment of chronic extremity pain in failed lumbar surgery. The role of lumbar sympathectomy. Persistent lower extremity pain after unsuccessful lumbar surgery continues to be a disabling condition. The results of deafferentation procedures for radiculopathy have been disappointing. Hence, the prospect of isolating a potentially reversible component of extremity pain is quite attractive. Given the frequency with which vasomotor complaints occur in this setting, the occurrence of autonomic dysfunction seems quite plausible. Autonomic dysfunction was investigated in 17 patients who had undergone previous lumbar surgery and had chronic limb pain. Patients underwent a preblockade thermogram, sympathetic blockade, and postblockade thermograms. All patients reported substantial relief after blockade, and all underwent retroperitoneal sympathectomy. All patients were followed for at least 2 years. The clinical results were disappointing, with only one patient reporting substantial relief. Although the results of thermography initially seemed to correlate with clinical outcome, further follow-up failed to yield any correlation. Additionally, no specific combination of response to blockade or thermogram was predictive of the clinical success after sympathectomy. Now, lumbar sympathectomy is not recommended in the setting of chronic radiculopathy and persistent extremity pain."} {"id": "PMID:1281930", "title": "Thrombin enhances tumor cell adhesive and metastatic properties via increased alpha IIb beta 3 expression on the cell surface.", "content": "The association between blood coagulation and cancer growth and metastatic dissemination is not yet completely understood. In this study we demonstrate that thrombin is capable of enhancing tumor cell adhesive properties and thereby increases tumor cell metastatic potential. Following exposure to alpha-thrombin, Walker 256 carcinosarcoma cells and B16 amelanotic melanoma cells became more adherent to both endothelial cell monolayers and the subendothelial matrix component, fibronectin. Preincubation of W256 and B16a cells with doses of alpha-thrombin from 0.01 to 10.0 U/ml produced a bell shape dose-response curve with the maximal effect (a 2-5-fold increase in adhesion) observed at 0.1 U/ml (corresponding to 0.8 nM). Complexes of alpha-thrombin with its inhibitors, hirudin and antithrombin III-heparin, diminished its effect on tumor cell adhesion. The effect of thrombin on tumor cell adhesion may be mediated by the alpha IIb beta 3 integrin as thrombin increased cell surface expression of the alpha IIb beta 3 complex. The significance of the in vitro observations was further substantiated by results of in vivo studies. Pretreatment of B16a cells with alpha-thrombin resulted in a 2-fold increase in the number of metastatic lung colonies in an experimental metastasis model. The data indicate a new role for thrombin in the metastatic spread of cancer.", "contents": "Thrombin enhances tumor cell adhesive and metastatic properties via increased alpha IIb beta 3 expression on the cell surface. The association between blood coagulation and cancer growth and metastatic dissemination is not yet completely understood. In this study we demonstrate that thrombin is capable of enhancing tumor cell adhesive properties and thereby increases tumor cell metastatic potential. Following exposure to alpha-thrombin, Walker 256 carcinosarcoma cells and B16 amelanotic melanoma cells became more adherent to both endothelial cell monolayers and the subendothelial matrix component, fibronectin. Preincubation of W256 and B16a cells with doses of alpha-thrombin from 0.01 to 10.0 U/ml produced a bell shape dose-response curve with the maximal effect (a 2-5-fold increase in adhesion) observed at 0.1 U/ml (corresponding to 0.8 nM). Complexes of alpha-thrombin with its inhibitors, hirudin and antithrombin III-heparin, diminished its effect on tumor cell adhesion. The effect of thrombin on tumor cell adhesion may be mediated by the alpha IIb beta 3 integrin as thrombin increased cell surface expression of the alpha IIb beta 3 complex. The significance of the in vitro observations was further substantiated by results of in vivo studies. Pretreatment of B16a cells with alpha-thrombin resulted in a 2-fold increase in the number of metastatic lung colonies in an experimental metastasis model. The data indicate a new role for thrombin in the metastatic spread of cancer."} {"id": "PMID:1281931", "title": "[Dystrophy caused by upper airway obstruction].", "content": "We describe three infants whose main symptoms were poor weight gain, delayed motor development and recurrent respiratory infections. Obstructive sleep apnea was diagnosed, and all three improved after adenotomy or adenotonsillectomy. Obstructive sleep apnea is an important differential diagnosis in infants showing retarded development and failure to thrive.", "contents": "[Dystrophy caused by upper airway obstruction]. We describe three infants whose main symptoms were poor weight gain, delayed motor development and recurrent respiratory infections. Obstructive sleep apnea was diagnosed, and all three improved after adenotomy or adenotonsillectomy. Obstructive sleep apnea is an important differential diagnosis in infants showing retarded development and failure to thrive."} {"id": "PMID:1281933", "title": "New polymorphic HLA-DR epitopes recognized by three monoclonal antibodies produced against DR103 transfected L cells.", "content": "Production of monoclonal antibodies directed against polymorphic epitopes of HLA class II molecules using whole human cells as immunogen has often proved ineffective, because most of the antibodies produced are directed against non-MHC human cell surface molecules. One approach to overcome this problem is the use of transfected mouse L cells expressing a single HLA class II allele as immunogen. By immunizing C3H mice with DR103-transfected L cells, we obtained 3 mAb, OHA TM901, OHA TM902, and OHA TM903, that recognize different polymorphic epitopes of the HLA-DR molecule. The molecular specificities of the 3 mAb were determined on a large panel of B-lymphoblastoid cell lines (B-LCL), peripheral blood cells and HLA class II transfectants from the XIth International Histocompatibility Workshop. Interestingly, the 3 polymorphic mAb detect new HLA-DR epitopes shared by several specificities: OHA TM901 reacts with DR1 (DR101, DR103), DR9 (DR901) and DR10 (DR1001) molecules; OHA TM902 recognizes the same molecules but also DR8 (DR801, 802, 803); OHA TM903 reacts with all DR types except DR3 (DR301, 302), DR7 (DR701, 702) and DR52. Surprisingly, OHA TM901 reacts with DR9 transfectants and B-LCL but not with DR9 peripheral blood lymphocytes. Biochemical analyses indicate that the 3 mAb immunoprecipitate HLA-DR products and react in western blots with DR alpha/beta-dimer but not with free alpha- or beta-chains. This study shows that transfected L cells are very useful tools for the production and the fine characterization of mAb recognizing polymorphic epitopes of HLA class II molecules.", "contents": "New polymorphic HLA-DR epitopes recognized by three monoclonal antibodies produced against DR103 transfected L cells. Production of monoclonal antibodies directed against polymorphic epitopes of HLA class II molecules using whole human cells as immunogen has often proved ineffective, because most of the antibodies produced are directed against non-MHC human cell surface molecules. One approach to overcome this problem is the use of transfected mouse L cells expressing a single HLA class II allele as immunogen. By immunizing C3H mice with DR103-transfected L cells, we obtained 3 mAb, OHA TM901, OHA TM902, and OHA TM903, that recognize different polymorphic epitopes of the HLA-DR molecule. The molecular specificities of the 3 mAb were determined on a large panel of B-lymphoblastoid cell lines (B-LCL), peripheral blood cells and HLA class II transfectants from the XIth International Histocompatibility Workshop. Interestingly, the 3 polymorphic mAb detect new HLA-DR epitopes shared by several specificities: OHA TM901 reacts with DR1 (DR101, DR103), DR9 (DR901) and DR10 (DR1001) molecules; OHA TM902 recognizes the same molecules but also DR8 (DR801, 802, 803); OHA TM903 reacts with all DR types except DR3 (DR301, 302), DR7 (DR701, 702) and DR52. Surprisingly, OHA TM901 reacts with DR9 transfectants and B-LCL but not with DR9 peripheral blood lymphocytes. Biochemical analyses indicate that the 3 mAb immunoprecipitate HLA-DR products and react in western blots with DR alpha/beta-dimer but not with free alpha- or beta-chains. This study shows that transfected L cells are very useful tools for the production and the fine characterization of mAb recognizing polymorphic epitopes of HLA class II molecules."} {"id": "PMID:1281934", "title": "Possible mechanism for zinc protection against cadmium cytotoxicity in cultured vascular endothelial cells.", "content": "We investigated the effect of zinc on cadmium cytotoxicity in vascular endothelial cells in a culture system. The cytotoxicity was evaluated by [3H]adenine release assay. Cadmium at 2 microM concentration and above significantly increased the [3H]adenine release, but zinc at 80 microM and below did not induce such a response after a 24-h incubation. Metallothionein was induced by cadmium at 0.1 microM and above but not by zinc at 300 microM and below; however, zinc at 10 microM and above significantly decreased cadmium-(2 and 5 microM) induced cytotoxicity. Zinc protection against cadmium cytotoxicity was also observed in the presence of 1 microM cycloheximide. Zinc caused significantly less accumulation of cadmium in the cell layer accompanied with a significant accumulation of zinc. The distribution (%) of cadmium in the particulate fraction of the cells was significantly decreased by zinc. In contrast, cadmium in the cytosol fraction was increased in the cells treated with both cadmium and zinc. Gel filtration chromatography of the cytosol showed that cadmium was capable of being bound to high-molecular-weight proteins and metallothionein. The metallothionein-bound cadmium was not increased by zinc; however, the relative distribution of cadmium in the high-molecular-weight fraction in the cytosol was decreased in cadmium plus zinc-treated cells. From these results, it was suggested that the mechanism by which zinc protects endothelial cells from cadmium cytotoxicity was decreased accumulation of cadmium in the particulate fraction and in the high-molecular-weight fraction in the cytosol of the cells. This alteration is postulated to be caused by both zinc-induced decrease in the intracellular cadmium accumulation and the sequestration of cadmium by cadmium-induced metallothionein.", "contents": "Possible mechanism for zinc protection against cadmium cytotoxicity in cultured vascular endothelial cells. We investigated the effect of zinc on cadmium cytotoxicity in vascular endothelial cells in a culture system. The cytotoxicity was evaluated by [3H]adenine release assay. Cadmium at 2 microM concentration and above significantly increased the [3H]adenine release, but zinc at 80 microM and below did not induce such a response after a 24-h incubation. Metallothionein was induced by cadmium at 0.1 microM and above but not by zinc at 300 microM and below; however, zinc at 10 microM and above significantly decreased cadmium-(2 and 5 microM) induced cytotoxicity. Zinc protection against cadmium cytotoxicity was also observed in the presence of 1 microM cycloheximide. Zinc caused significantly less accumulation of cadmium in the cell layer accompanied with a significant accumulation of zinc. The distribution (%) of cadmium in the particulate fraction of the cells was significantly decreased by zinc. In contrast, cadmium in the cytosol fraction was increased in the cells treated with both cadmium and zinc. Gel filtration chromatography of the cytosol showed that cadmium was capable of being bound to high-molecular-weight proteins and metallothionein. The metallothionein-bound cadmium was not increased by zinc; however, the relative distribution of cadmium in the high-molecular-weight fraction in the cytosol was decreased in cadmium plus zinc-treated cells. From these results, it was suggested that the mechanism by which zinc protects endothelial cells from cadmium cytotoxicity was decreased accumulation of cadmium in the particulate fraction and in the high-molecular-weight fraction in the cytosol of the cells. This alteration is postulated to be caused by both zinc-induced decrease in the intracellular cadmium accumulation and the sequestration of cadmium by cadmium-induced metallothionein."} {"id": "PMID:1281935", "title": "Pathophysiology of chemical injury of the thyroid gland.", "content": "Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis and secretion of thyroid hormones. This includes: (1) inhibition of the iodine trapping mechanism (thiocyanate or perchlorate); (2) blockage of organic binding of iodine and coupling of iodothyronines to form thyroxine (T4) and triiodothyronine (T3) (e.g. sulfonamides, thiourea, methimazole, and aminotriazole, amongst others); (3) inhibition of thyroid hormone secretion by an effect on proteolysis of active hormone from the colloid (lithium or an excess of iodide). Another large group of goitrogenic chemicals disrupts thyroid hormone economy by increasing the peripheral metabolism of thyroid hormones through an induction of hepatic microsomal enzymes. This group includes CNS-acting drugs (phenobarbital, benzodiazepines), calcium channel blockers (nicardipine, nifedipine), steroids (spironolactone), retinoids, chlorinated hydrocarbons (chlordane, DDT, TCDD), polyhalogenated biphenyls (PCB, PBB), and enzyme inducers. Thyroid hormone economy also can be disrupted by xenobiotics that inhibit the 5'-monodeiodinase which converts T4 in peripheral sites (e.g. liver and kidney) to biologically active T3. Inhibition of this enzyme by FD&C Red No. 3, amiodarone, and iopanoic acid lowers circulating T3 levels which results in a compensatory increased secretion of thyroid stimulating hormone (TSH), follicular cell hypertrophy and hyperplasia, and an increased incidence of follicular cell tumors in 2-year or lifetime studies in rats. Physiologic perturbations alone, such as the feeding of an iodine-deficient diet, partial thyroidectomy, natural goitrogens in certain foods, and transplantation of TSH-secreting pituitary tumors in rodents also can disrupt thyroid hormone economy and, if sustained, increase the development of thyroid tumors in rats. A consistent finding with all of these goitrogens, be they either physiologic perturbations or xenobiotics, is the chronic hypersecretion of TSH which places the rodent thyroid gland at greater risk to develop tumors through a secondary mechanism of thyroid oncogenesis.", "contents": "Pathophysiology of chemical injury of the thyroid gland. Many goitrogenic xenobiotics that increase the incidence of thyroid tumors in rodents exert a direct effect on the thyroid gland to disrupt one of several possible steps in the biosynthesis and secretion of thyroid hormones. This includes: (1) inhibition of the iodine trapping mechanism (thiocyanate or perchlorate); (2) blockage of organic binding of iodine and coupling of iodothyronines to form thyroxine (T4) and triiodothyronine (T3) (e.g. sulfonamides, thiourea, methimazole, and aminotriazole, amongst others); (3) inhibition of thyroid hormone secretion by an effect on proteolysis of active hormone from the colloid (lithium or an excess of iodide). Another large group of goitrogenic chemicals disrupts thyroid hormone economy by increasing the peripheral metabolism of thyroid hormones through an induction of hepatic microsomal enzymes. This group includes CNS-acting drugs (phenobarbital, benzodiazepines), calcium channel blockers (nicardipine, nifedipine), steroids (spironolactone), retinoids, chlorinated hydrocarbons (chlordane, DDT, TCDD), polyhalogenated biphenyls (PCB, PBB), and enzyme inducers. Thyroid hormone economy also can be disrupted by xenobiotics that inhibit the 5'-monodeiodinase which converts T4 in peripheral sites (e.g. liver and kidney) to biologically active T3. Inhibition of this enzyme by FD&C Red No. 3, amiodarone, and iopanoic acid lowers circulating T3 levels which results in a compensatory increased secretion of thyroid stimulating hormone (TSH), follicular cell hypertrophy and hyperplasia, and an increased incidence of follicular cell tumors in 2-year or lifetime studies in rats. Physiologic perturbations alone, such as the feeding of an iodine-deficient diet, partial thyroidectomy, natural goitrogens in certain foods, and transplantation of TSH-secreting pituitary tumors in rodents also can disrupt thyroid hormone economy and, if sustained, increase the development of thyroid tumors in rats. A consistent finding with all of these goitrogens, be they either physiologic perturbations or xenobiotics, is the chronic hypersecretion of TSH which places the rodent thyroid gland at greater risk to develop tumors through a secondary mechanism of thyroid oncogenesis."} {"id": "PMID:1281936", "title": "Thyroid gland neoplasia: non-genotoxic mechanisms.", "content": "There are two basic mechanisms whereby chemicals produce thyroid gland neoplasia in rodents. The first involves chemicals that exert a direct carcinogenic effect in the thyroid gland and the other involves chemicals which, through a variety of mechanisms, disrupt thyroid function and produce thyroid gland neoplasia secondary to hormone imbalance. There are important species differences in thyroid gland physiology between rodents and humans which may account for a marked species difference in the inherent susceptibility for neoplasia secondary to hormone imbalance. Thus, it is important to consider mechanism in the evaluation of potential cancer risks. There would be little if any risk for apparently nongenotoxic chemicals that act secondary to hormone imbalance at exposure levels that do not disrupt thyroid function. Further, the degree of thyroid dysfunction produced by a chemical would present a major toxicological problem before such exposure would increase the risk for neoplasia for humans.", "contents": "Thyroid gland neoplasia: non-genotoxic mechanisms. There are two basic mechanisms whereby chemicals produce thyroid gland neoplasia in rodents. The first involves chemicals that exert a direct carcinogenic effect in the thyroid gland and the other involves chemicals which, through a variety of mechanisms, disrupt thyroid function and produce thyroid gland neoplasia secondary to hormone imbalance. There are important species differences in thyroid gland physiology between rodents and humans which may account for a marked species difference in the inherent susceptibility for neoplasia secondary to hormone imbalance. Thus, it is important to consider mechanism in the evaluation of potential cancer risks. There would be little if any risk for apparently nongenotoxic chemicals that act secondary to hormone imbalance at exposure levels that do not disrupt thyroid function. Further, the degree of thyroid dysfunction produced by a chemical would present a major toxicological problem before such exposure would increase the risk for neoplasia for humans."} {"id": "PMID:1281937", "title": "Sodium and GABA-activated channels as the targets of pyrethroids and cyclodienes.", "content": "The symptoms of poisoning by the pyrethroid and cyclodiene insecticides are characterized by hyperexcitation and convulsions followed by paralysis. The main target site of the pyrethroids has been identified to be the sodium channels which are kept open for unusually long periods of time, causing a prolonged sodium current to flow which, in turn, leads to hyperexcitation of the nervous system. We have now found large differential sensitivity to the pyrethroids in two types of sodium channels. The dorsal root ganglion neurons of the rat were endowed with two types of sodium channels, one sensitive to the blocking action of tetrodotoxin (TTX) and the other insensitive to TTX. The type I pyrethroid allethrin and the type II pyrethroid deltamethrin were both effective in prolonging the sodium current in the TXX-resistant sodium channel but had only a small effect on the TTX-sensitive sodium channel. These two types of sodium channels also exhibited marked differences in their physiological properties, including the time course of current, the activation voltage, and the steady-state inactivation. In contrast to the pyrethroids, lindane and the cyclodienes endrin, isobenzan, dieldrin and heptachlor-epoxide suppressed the GABA-induced chloride current. The initial transient component of the chloride current was blocked more than the late sustained component. The suppression of the GABA-mediated synaptic inhibition would cause hyperexcitation of the nervous system. The results are compatible with the convulsant action of these insecticides.", "contents": "Sodium and GABA-activated channels as the targets of pyrethroids and cyclodienes. The symptoms of poisoning by the pyrethroid and cyclodiene insecticides are characterized by hyperexcitation and convulsions followed by paralysis. The main target site of the pyrethroids has been identified to be the sodium channels which are kept open for unusually long periods of time, causing a prolonged sodium current to flow which, in turn, leads to hyperexcitation of the nervous system. We have now found large differential sensitivity to the pyrethroids in two types of sodium channels. The dorsal root ganglion neurons of the rat were endowed with two types of sodium channels, one sensitive to the blocking action of tetrodotoxin (TTX) and the other insensitive to TTX. The type I pyrethroid allethrin and the type II pyrethroid deltamethrin were both effective in prolonging the sodium current in the TXX-resistant sodium channel but had only a small effect on the TTX-sensitive sodium channel. These two types of sodium channels also exhibited marked differences in their physiological properties, including the time course of current, the activation voltage, and the steady-state inactivation. In contrast to the pyrethroids, lindane and the cyclodienes endrin, isobenzan, dieldrin and heptachlor-epoxide suppressed the GABA-induced chloride current. The initial transient component of the chloride current was blocked more than the late sustained component. The suppression of the GABA-mediated synaptic inhibition would cause hyperexcitation of the nervous system. The results are compatible with the convulsant action of these insecticides."} {"id": "PMID:1281938", "title": "Use of white rot fungi in the degradation of environmental chemicals.", "content": "White rot fungi have been shown to mineralize a wide variety of environmental pollutants. These fungi secrete a number of enzymes that are involved in its unique ability to degrade lignin, the structural component of woody plants. Lignin is a very complex heteropolymer that can only be degraded by white rot fungi. Degradation is complete without energy value to the fungus. The evolution of this ability has apparently given the organism the ability to degrade structurally diverse and normally very recalcitrant environmental pollutants such as DDT, PCB, benzo(a)pyrene, TNT, etc. Some of the major enzymes that are secreted by the fungi are peroxidases with unique properties. In addition to their ability to catalyze a wide variety of oxidations, they can also catalyze indirect oxidations and reductions. The fungi synthesize and secrete hydrogen peroxide to activate the peroxidases, veratryl alcohol to serve as a free radical intermediate for indirect oxidations, and electron donors, such as oxalate, which with veratryl alcohol catalyze reductions. Reductions are often required for subsequent oxidation of chemicals by the peroxidases. The enzymes can also reduce molecular oxygen.", "contents": "Use of white rot fungi in the degradation of environmental chemicals. White rot fungi have been shown to mineralize a wide variety of environmental pollutants. These fungi secrete a number of enzymes that are involved in its unique ability to degrade lignin, the structural component of woody plants. Lignin is a very complex heteropolymer that can only be degraded by white rot fungi. Degradation is complete without energy value to the fungus. The evolution of this ability has apparently given the organism the ability to degrade structurally diverse and normally very recalcitrant environmental pollutants such as DDT, PCB, benzo(a)pyrene, TNT, etc. Some of the major enzymes that are secreted by the fungi are peroxidases with unique properties. In addition to their ability to catalyze a wide variety of oxidations, they can also catalyze indirect oxidations and reductions. The fungi synthesize and secrete hydrogen peroxide to activate the peroxidases, veratryl alcohol to serve as a free radical intermediate for indirect oxidations, and electron donors, such as oxalate, which with veratryl alcohol catalyze reductions. Reductions are often required for subsequent oxidation of chemicals by the peroxidases. The enzymes can also reduce molecular oxygen."} {"id": "PMID:1281939", "title": "Paracetamol toxicity and its prevention by cytoprotection with iloprost.", "content": "In a well-established two phase model of paracetamol toxicity in hamster hepatocytes cell death was accompanied, but not preceded, by a rise in cytosolic free calcium [Ca2+]i. Cell death appears to involve reversible oxidative damage, possibly to the cytoskeleton or mitochondria. In this model low concentrations (10(-8) to 10(-14) M) of iloprost, a stable analogue of prostacyclin, offered protection against the toxic effects of paracetamol. In preliminary studies with a rat liver epithelial cell line transduced with murine P4501A2 the toxicity of paracetamol was attenuated by iloprost. Inhibition of protein synthesis with cycloheximide had no effect on paracetamol toxicity but abolished the cytoprotective effect of iloprost.", "contents": "Paracetamol toxicity and its prevention by cytoprotection with iloprost. In a well-established two phase model of paracetamol toxicity in hamster hepatocytes cell death was accompanied, but not preceded, by a rise in cytosolic free calcium [Ca2+]i. Cell death appears to involve reversible oxidative damage, possibly to the cytoskeleton or mitochondria. In this model low concentrations (10(-8) to 10(-14) M) of iloprost, a stable analogue of prostacyclin, offered protection against the toxic effects of paracetamol. In preliminary studies with a rat liver epithelial cell line transduced with murine P4501A2 the toxicity of paracetamol was attenuated by iloprost. Inhibition of protein synthesis with cycloheximide had no effect on paracetamol toxicity but abolished the cytoprotective effect of iloprost."} {"id": "PMID:1281940", "title": "The clinical toxicology of chlordecone as an example of toxicological risk assessment for man.", "content": "Safety assessment procedures still rely heavily if not exclusively on the results of tests carried out in laboratory animals, then extrapolated to man. There are few examples of environmental compounds examined extensively enough in both man and animals to permit a critical comparison of the accuracy of such risk assessment procedures. Chlordecone (Kepone) is a lipophilic, rodent liver carcinogen which now stands among the most extensively studied environmental agents in humans. More than five years of clinical investigations of workers heavily exposed to organochlorine pesticide have established the spectrum of human toxicity of Chlordecone, its dose-response relationships, tissue distribution, metabolic pathways, half-time for elimination, and the concentration at which its major toxic manifestations involving the central nervous system, the liver, and the testes are not observed (no observable effect level, NOEL). Taking advantage of this unique opportunity to proximately compare humans with experimental animals for a single compound administered at comparable doses, we find that none of the toxic effects produced in humans were unrepresented in animal testing. However, the animal testing produced numerous \"false positive\" results. Hence, accurately predicting the qualitative toxicity of chlordecone in man based on studies in rats would have been impossible. Indeed, proteinuria observed in rats fed small amounts of chlordecone for two years was chosen as a sensitive endpoint by the United States Environmental Protection Agency as the basis for establishing acceptable levels of human exposure. However, we never observed proteinuria even in humans whose dose of chlordecone was hundreds of times higher than that given to the rats. We conclude that greater emphasis should be placed on clinical investigation of humans exposed to environmental agents. A better understanding of the strength and also of the limitations of animal toxicity testing will improve the reliability of extrapolating results of animal testing to human exposure conditions.", "contents": "The clinical toxicology of chlordecone as an example of toxicological risk assessment for man. Safety assessment procedures still rely heavily if not exclusively on the results of tests carried out in laboratory animals, then extrapolated to man. There are few examples of environmental compounds examined extensively enough in both man and animals to permit a critical comparison of the accuracy of such risk assessment procedures. Chlordecone (Kepone) is a lipophilic, rodent liver carcinogen which now stands among the most extensively studied environmental agents in humans. More than five years of clinical investigations of workers heavily exposed to organochlorine pesticide have established the spectrum of human toxicity of Chlordecone, its dose-response relationships, tissue distribution, metabolic pathways, half-time for elimination, and the concentration at which its major toxic manifestations involving the central nervous system, the liver, and the testes are not observed (no observable effect level, NOEL). Taking advantage of this unique opportunity to proximately compare humans with experimental animals for a single compound administered at comparable doses, we find that none of the toxic effects produced in humans were unrepresented in animal testing. However, the animal testing produced numerous \"false positive\" results. Hence, accurately predicting the qualitative toxicity of chlordecone in man based on studies in rats would have been impossible. Indeed, proteinuria observed in rats fed small amounts of chlordecone for two years was chosen as a sensitive endpoint by the United States Environmental Protection Agency as the basis for establishing acceptable levels of human exposure. However, we never observed proteinuria even in humans whose dose of chlordecone was hundreds of times higher than that given to the rats. We conclude that greater emphasis should be placed on clinical investigation of humans exposed to environmental agents. A better understanding of the strength and also of the limitations of animal toxicity testing will improve the reliability of extrapolating results of animal testing to human exposure conditions."} {"id": "PMID:1281941", "title": "Mechanism of pain induced by radiocontrast media.", "content": "In lightly-anesthetized dogs, ionic or non-ionic RCM (Iotalamato and iohexol, respectively) when injected by intracarotid route (i.c.), elicit a pain response comparable to that caused by bradykinin (BK) or capsaicin (CAP). This response, which is characterized by vocalization, hyperpnea, bradycardia and neck muscle contraction, was dose dependent and related to the osmolarity of the RCM. In the present study we observed that indomethacin did not interfere with CAP and RCM-induced pain at dose (2 mg/kg i.c.) that reduced BK-elicited responses. In contrast, Ruthenium Red (RR), in dose (1 mg/kg i.c.) that reduced CAP and/or RCM-induced effects did not affect BK-induced phenomena. We also verified that L-NAME (50 mg/kg i.c.) reduced the BK-, but not the CAP- and/or RCM-induced pain responses which suggests that an L-arginine-derived NO or related compound is involved in BK activation of perivascular nociceptors. Indeed, we found that i.c. injection of 20 mg of S-nitrosocysteine, a putative EDRF, caused BK-like responses. On the other hand, RCM and CAP appear to activate the same RR sensitive ionic channels of primary afferent endings. Therefore, RR-analogues could constitute a novel approach to minimizing or eventually abolishing the RCM side effects.", "contents": "Mechanism of pain induced by radiocontrast media. In lightly-anesthetized dogs, ionic or non-ionic RCM (Iotalamato and iohexol, respectively) when injected by intracarotid route (i.c.), elicit a pain response comparable to that caused by bradykinin (BK) or capsaicin (CAP). This response, which is characterized by vocalization, hyperpnea, bradycardia and neck muscle contraction, was dose dependent and related to the osmolarity of the RCM. In the present study we observed that indomethacin did not interfere with CAP and RCM-induced pain at dose (2 mg/kg i.c.) that reduced BK-elicited responses. In contrast, Ruthenium Red (RR), in dose (1 mg/kg i.c.) that reduced CAP and/or RCM-induced effects did not affect BK-induced phenomena. We also verified that L-NAME (50 mg/kg i.c.) reduced the BK-, but not the CAP- and/or RCM-induced pain responses which suggests that an L-arginine-derived NO or related compound is involved in BK activation of perivascular nociceptors. Indeed, we found that i.c. injection of 20 mg of S-nitrosocysteine, a putative EDRF, caused BK-like responses. On the other hand, RCM and CAP appear to activate the same RR sensitive ionic channels of primary afferent endings. Therefore, RR-analogues could constitute a novel approach to minimizing or eventually abolishing the RCM side effects."} {"id": "PMID:1281942", "title": "Expression of blood group antigens on red cell microvesicles.", "content": "The purpose of this study was to determine whether epitopes of the A, B, D, Fya, M, N, S, s, and K blood group antigens are present on microvesicle membranes shed by red cells during storage. Vesicles were isolated from outdated units of blood having and lacking the specified antigens. Diluted antisera were absorbed with fixed quantities of vesicles from red cells with the test antigen and red cells lacking that antigen (controls). The adsorbed and unadsorbed antisera were titrated and scored by using panel cells from persons known to be heterozygous for all the non-AB antigens. The mean titration scores following adsorption with the vesicles from A, B, D, M+N-, M-N+, S+s-, S-s+, and Fy(a+b-) units were appreciably lower than the control scores (0, 0, 3, 2, 2, 0, 4, and 4 vs. 19, 23, 34, 13, 12, 16, 18, and 29, respectively), which indicated the presence of these epitopes on the membrane of shed vesicles. The results following adsorption with K:1,2 vesicles were equivocal.", "contents": "Expression of blood group antigens on red cell microvesicles. The purpose of this study was to determine whether epitopes of the A, B, D, Fya, M, N, S, s, and K blood group antigens are present on microvesicle membranes shed by red cells during storage. Vesicles were isolated from outdated units of blood having and lacking the specified antigens. Diluted antisera were absorbed with fixed quantities of vesicles from red cells with the test antigen and red cells lacking that antigen (controls). The adsorbed and unadsorbed antisera were titrated and scored by using panel cells from persons known to be heterozygous for all the non-AB antigens. The mean titration scores following adsorption with the vesicles from A, B, D, M+N-, M-N+, S+s-, S-s+, and Fy(a+b-) units were appreciably lower than the control scores (0, 0, 3, 2, 2, 0, 4, and 4 vs. 19, 23, 34, 13, 12, 16, 18, and 29, respectively), which indicated the presence of these epitopes on the membrane of shed vesicles. The results following adsorption with K:1,2 vesicles were equivocal."} {"id": "PMID:1281943", "title": "Monocyte chemotaxis and chemotactic cytokine release after exposure to hydroxyethyl starch.", "content": "Hydroxyethyl starch (HES) is commonly used in leukapheresis and infused as an alternative to blood components for the treatment of hypotension due to hemorrhage and trauma. Its prolonged intravascular persistence and retention in tissue raise concerns about possible effects on humoral and cell-mediated immunity and white cell (WBC) locomotion, particularly in volunteer WBC donors or in severely burned individuals with immunologic depression and increased risk for infection. This study evaluated the effect of HES on human monocyte migration and chemotaxis and the production of antigen- and mitogen-induced WBC-derived chemotactic cytokine. A bioassay was developed to quantitate the neutrophil chemotactic activity of a cytokine generated by mononuclear WBCs stimulated in vitro by phytohemagglutinin or tuberculin protein. The time- and dose-dependent generation of the chemotactic cytokine was not affected by the presence of HES. HES by itself did not induce the generation of this cytokine, nor were human monocyte chemotaxis and spontaneous migration significantly changed by exposure to HES. These results, with those of other investigators, suggest that HES is a safe red cell-sedimenting agent for leukapheresis and an alternative to the use of blood components in shock resuscitation.", "contents": "Monocyte chemotaxis and chemotactic cytokine release after exposure to hydroxyethyl starch. Hydroxyethyl starch (HES) is commonly used in leukapheresis and infused as an alternative to blood components for the treatment of hypotension due to hemorrhage and trauma. Its prolonged intravascular persistence and retention in tissue raise concerns about possible effects on humoral and cell-mediated immunity and white cell (WBC) locomotion, particularly in volunteer WBC donors or in severely burned individuals with immunologic depression and increased risk for infection. This study evaluated the effect of HES on human monocyte migration and chemotaxis and the production of antigen- and mitogen-induced WBC-derived chemotactic cytokine. A bioassay was developed to quantitate the neutrophil chemotactic activity of a cytokine generated by mononuclear WBCs stimulated in vitro by phytohemagglutinin or tuberculin protein. The time- and dose-dependent generation of the chemotactic cytokine was not affected by the presence of HES. HES by itself did not induce the generation of this cytokine, nor were human monocyte chemotaxis and spontaneous migration significantly changed by exposure to HES. These results, with those of other investigators, suggest that HES is a safe red cell-sedimenting agent for leukapheresis and an alternative to the use of blood components in shock resuscitation."} {"id": "PMID:1281944", "title": "[Factors that cause a change in the antigenic structure of of the influenza virus hemagglutinin].", "content": "Crossing of norakin-resistant mutant NR1 of A/Waybridge (H7N7) strain of fowl plague virus (FPV) with human influenza virus strains produced recombinants inheriting the hemagglutinin (HA) gene of the NR1 mutant and neuraminidase (NA) genes of human influenza virus strains. The R120 recombinant produced by crossing of NR1 with A/Taiwan/1/86 (H1N1) strain, unlike other recombinants and NR1 mutant, lost the capacity of reacting in H1 test with two monoclonal antibodies (MCA) to HA7: 71/4 and 46/6. The ts mutant A/FPV/Rostok which has ts-mutation in HA-gene also had changes in the antigenic specificity of HA. The RA and RB recombinants produced by crossing R120 with the A/Krasnodar/101/59 strain and inheriting HA-gene from R120 and NA-gene from A/Krasnodar/101/59 strain recovered the initial HA antigenic structure. No changes in the antigenic properties of HA were observed in the recombinants produced by crossing the original A/FPV/Waybridge strain with A/Taiwan/1/86 strain and inheriting HA-gene from the original A/FPV/Waybridge strain and NA-gene from A/Taiwan/1/86 strain. It is concluded that ts mutations in influenza virus HA-gene may be accompanied by changes in the antigenic specificity of this virus HA. The possibilities of manifestation of phenotypic suppression at the level of influenza virus virion membrane proteins and the causes of changes in the HA antigenic structure in this virus recombinants are discussed.", "contents": "[Factors that cause a change in the antigenic structure of of the influenza virus hemagglutinin]. Crossing of norakin-resistant mutant NR1 of A/Waybridge (H7N7) strain of fowl plague virus (FPV) with human influenza virus strains produced recombinants inheriting the hemagglutinin (HA) gene of the NR1 mutant and neuraminidase (NA) genes of human influenza virus strains. The R120 recombinant produced by crossing of NR1 with A/Taiwan/1/86 (H1N1) strain, unlike other recombinants and NR1 mutant, lost the capacity of reacting in H1 test with two monoclonal antibodies (MCA) to HA7: 71/4 and 46/6. The ts mutant A/FPV/Rostok which has ts-mutation in HA-gene also had changes in the antigenic specificity of HA. The RA and RB recombinants produced by crossing R120 with the A/Krasnodar/101/59 strain and inheriting HA-gene from R120 and NA-gene from A/Krasnodar/101/59 strain recovered the initial HA antigenic structure. No changes in the antigenic properties of HA were observed in the recombinants produced by crossing the original A/FPV/Waybridge strain with A/Taiwan/1/86 strain and inheriting HA-gene from the original A/FPV/Waybridge strain and NA-gene from A/Taiwan/1/86 strain. It is concluded that ts mutations in influenza virus HA-gene may be accompanied by changes in the antigenic specificity of this virus HA. The possibilities of manifestation of phenotypic suppression at the level of influenza virus virion membrane proteins and the causes of changes in the HA antigenic structure in this virus recombinants are discussed."} {"id": "PMID:1281945", "title": "[The isolation and characteristics of monoclonal antibodies to different proteins of the herpes simplex virus types 1 and 2].", "content": "The authors prepared 156 mouse hybridomas producing monoclonal (MCA) antibodies to type- and group-specific antigenic determinants of HSV-1 and HSV-2. Seven of them were studied at length by western blot and radioimmunoprecipitation methods. The cell lines 1H97 and 2H141 were shown to produce immunoglobulins of G2 beta and M class, respectively, and were directed against group-specific antigenic determinants of the major nucleocapsid protein p150. The cell lines 1H38 and 1H110 produced immunoglobulins of M and G2 beta, respectively, and were directed against type-specific antigens of HSV-1 glycoprotein gB. At the same time, the presence of group-specific antigenic determinants on glycoprotein gB molecule was indicated by MCA 1H188 belonging to immunoglobulins of G2 alpha class. Two cell lines, 2H208 and 1H225, produced immunoglobulins G2 alpha directed against type-specific antigenic determinants of HSV-2 glycoprotein gD and group-specific antigenic determinants of HSV-1 gD, respectively. The results of immunoelectron microscopy indicated that MCA 1H110 and 2H208 were directed against virus envelope proteins.", "contents": "[The isolation and characteristics of monoclonal antibodies to different proteins of the herpes simplex virus types 1 and 2]. The authors prepared 156 mouse hybridomas producing monoclonal (MCA) antibodies to type- and group-specific antigenic determinants of HSV-1 and HSV-2. Seven of them were studied at length by western blot and radioimmunoprecipitation methods. The cell lines 1H97 and 2H141 were shown to produce immunoglobulins of G2 beta and M class, respectively, and were directed against group-specific antigenic determinants of the major nucleocapsid protein p150. The cell lines 1H38 and 1H110 produced immunoglobulins of M and G2 beta, respectively, and were directed against type-specific antigens of HSV-1 glycoprotein gB. At the same time, the presence of group-specific antigenic determinants on glycoprotein gB molecule was indicated by MCA 1H188 belonging to immunoglobulins of G2 alpha class. Two cell lines, 2H208 and 1H225, produced immunoglobulins G2 alpha directed against type-specific antigenic determinants of HSV-2 glycoprotein gD and group-specific antigenic determinants of HSV-1 gD, respectively. The results of immunoelectron microscopy indicated that MCA 1H110 and 2H208 were directed against virus envelope proteins."} {"id": "PMID:1281948", "title": "Development of a vaccine for the prevention of AIDS, a critical appraisal.", "content": "The pathogenesis and clinical expression of HIV-1 infection in humans is considered in terms of classical pathogenetic studies of viral infections for which successful vaccines have been produced. The unique features of HIV pathogenesis are defined, and gaps in knowledge identified as a framework for considering designs for immune intervention. Envelope-derived candidate vaccines have been used in immunization and challenge experiments in SIV/macaque or HIV/chimpanzee models, presented either as vaccinia recombinant vectors or as subunits, singly or in sequence. These studies have been paralleled by clinical trials for safety and immunogenicity in seronegative individuals. Data generated will permit comparison of immune responses to specific antigens and delivery systems in animal models and in humans. In limited studies conducted under optimized conditions, non-human primates have been protected against virus challenge when immunized with some candidate vaccines or following passive transfer of high-titred antibody. Consideration of current information suggests that in order to prevent HIV infection it may be necessary to devise new strategies capable of inducing and maintaining high threshold titres of biologically relevant antibody as well as persistence of active cytotoxic T cells recognizing multiple epitopes.", "contents": "Development of a vaccine for the prevention of AIDS, a critical appraisal. The pathogenesis and clinical expression of HIV-1 infection in humans is considered in terms of classical pathogenetic studies of viral infections for which successful vaccines have been produced. The unique features of HIV pathogenesis are defined, and gaps in knowledge identified as a framework for considering designs for immune intervention. Envelope-derived candidate vaccines have been used in immunization and challenge experiments in SIV/macaque or HIV/chimpanzee models, presented either as vaccinia recombinant vectors or as subunits, singly or in sequence. These studies have been paralleled by clinical trials for safety and immunogenicity in seronegative individuals. Data generated will permit comparison of immune responses to specific antigens and delivery systems in animal models and in humans. In limited studies conducted under optimized conditions, non-human primates have been protected against virus challenge when immunized with some candidate vaccines or following passive transfer of high-titred antibody. Consideration of current information suggests that in order to prevent HIV infection it may be necessary to devise new strategies capable of inducing and maintaining high threshold titres of biologically relevant antibody as well as persistence of active cytotoxic T cells recognizing multiple epitopes."} {"id": "PMID:1281946", "title": "[The therapeutic effect of aprotinin inhalations in influenza and paramyxovirus infections in mice].", "content": "Mice infected with influenza A/Aichi/2/68 (H3N2) virus or Sendai/960 paramyxovirus were treated by inhalations of aerosol aprotinin, a broad spectrum inhibitor of proteinases. A course of inhalations of finely dispersed aerosol aprotinin including 4 exposures of 35-40 min each daily for 6 days provided respiratory administration of aprotinin in a dose about 100 kallikrein-inhibiting U/mouse per day. In mice treated by aprotinin inhalations, histological examinations showed decreased pulmonary pathology, and their body weights increased as much as in uninfected animals. In the placebo group, the weight decreased until the death of the animals. The protective effect of aprotinin inhalations was 40-80% with inoculation doses 10-100 MLD50/mouse. The treated animals died 2-4 days later than those in the placebo group. The results indicate the expedience of inhalation therapy with aerosol aprotinin in influenza and paramyxovirus respiratory infections.", "contents": "[The therapeutic effect of aprotinin inhalations in influenza and paramyxovirus infections in mice]. Mice infected with influenza A/Aichi/2/68 (H3N2) virus or Sendai/960 paramyxovirus were treated by inhalations of aerosol aprotinin, a broad spectrum inhibitor of proteinases. A course of inhalations of finely dispersed aerosol aprotinin including 4 exposures of 35-40 min each daily for 6 days provided respiratory administration of aprotinin in a dose about 100 kallikrein-inhibiting U/mouse per day. In mice treated by aprotinin inhalations, histological examinations showed decreased pulmonary pathology, and their body weights increased as much as in uninfected animals. In the placebo group, the weight decreased until the death of the animals. The protective effect of aprotinin inhalations was 40-80% with inoculation doses 10-100 MLD50/mouse. The treated animals died 2-4 days later than those in the placebo group. The results indicate the expedience of inhalation therapy with aerosol aprotinin in influenza and paramyxovirus respiratory infections."} {"id": "PMID:1281949", "title": "[Surgery of stomach cancer--an assessment of current status].", "content": "Surgical strategy for gastric carcinoma consists of total gastrectomy as a rule combined with extended lymphadenectomy. For small tumors of the intestinal type located in the distal stomach distal gastric resection can be taken into consideration. In case of a high risk patient endoscopic polypectomy of a polypoid early gastric carcinoma can be sufficient. If the operation is done for cure intraoperative radiotherapy is employed within prospective trials in order to prevent local recurrence. Extended resections prolong survival time only if curativity will be achieved. For palliative situations procedures including removal of the tumor have better results with regard to quality of life and survival than bypass methods.", "contents": "[Surgery of stomach cancer--an assessment of current status]. Surgical strategy for gastric carcinoma consists of total gastrectomy as a rule combined with extended lymphadenectomy. For small tumors of the intestinal type located in the distal stomach distal gastric resection can be taken into consideration. In case of a high risk patient endoscopic polypectomy of a polypoid early gastric carcinoma can be sufficient. If the operation is done for cure intraoperative radiotherapy is employed within prospective trials in order to prevent local recurrence. Extended resections prolong survival time only if curativity will be achieved. For palliative situations procedures including removal of the tumor have better results with regard to quality of life and survival than bypass methods."} {"id": "PMID:1281950", "title": "[Surgical emergency interventions in acute diseases of the large intestine].", "content": "Emergency operations due to acute colonic disease between 1. 1. 1984 and 31. 12. 1991 were retrospectively analyzed with regard to causality, surgical procedure, complications and mortality. 55 of 1105 colonic operations were emergency cases requiring immediate surgical intervention. Primary continuity preserving resections were carried out whenever possible, attending not only to the acute situation but also to the primary disease. The mean age of the 26 females and 29 males was 69 [1, 9] years. 29 patients had a colonic ileus, 21 a diffuse peritonitis and 5 patients had an uncontrolled haemorrhage. Colorectal carcinomas were initially diagnosed in 20 of the 50 patients; 14 of these patients (70%) could be operated for potential cure and primary continuity preserving resections were also possible for 14 patients (70%). Continuity preserving resections were possible for 18 of 21 patients with peritonitis and 3 colonic perforations were oversutured. In the 5 patients with acute haemorrhage, 4 resections and one transanal intervention were performed. Postoperative complications were observed in 19 patients (35%). Postoperative mortality was 16% (9/55), 5% for operations due to peritonitis, 24% for operations due to colonic ileus and 20% for operations due to haemorrhage. Primary continuity preserving resections were possible for 39 of 55 patients (71%).", "contents": "[Surgical emergency interventions in acute diseases of the large intestine]. Emergency operations due to acute colonic disease between 1. 1. 1984 and 31. 12. 1991 were retrospectively analyzed with regard to causality, surgical procedure, complications and mortality. 55 of 1105 colonic operations were emergency cases requiring immediate surgical intervention. Primary continuity preserving resections were carried out whenever possible, attending not only to the acute situation but also to the primary disease. The mean age of the 26 females and 29 males was 69 [1, 9] years. 29 patients had a colonic ileus, 21 a diffuse peritonitis and 5 patients had an uncontrolled haemorrhage. Colorectal carcinomas were initially diagnosed in 20 of the 50 patients; 14 of these patients (70%) could be operated for potential cure and primary continuity preserving resections were also possible for 14 patients (70%). Continuity preserving resections were possible for 18 of 21 patients with peritonitis and 3 colonic perforations were oversutured. In the 5 patients with acute haemorrhage, 4 resections and one transanal intervention were performed. Postoperative complications were observed in 19 patients (35%). Postoperative mortality was 16% (9/55), 5% for operations due to peritonitis, 24% for operations due to colonic ileus and 20% for operations due to haemorrhage. Primary continuity preserving resections were possible for 39 of 55 patients (71%)."} {"id": "PMID:1281947", "title": "[The degree of virulence in Far Eastern strains of the tick-borne encephalitis virus].", "content": "Screening of immunomodulating properties of 45 tick-borne encephalitis (TBE) virus strains isolated in the southern part of the Soviet Far East was carried out. TBE virus strains were found to have different effects on the immune responsiveness of host splenocytes. Over 90% of the strains isolated from hematothermals could inhibit the immune response of the host to a heterologous antigen (sheep erythrocytes); similar properties were found in 5 strains isolated from ticks. At the same time, most strains isolated from the vectors were unable to modulate the immune response of antibody-producing cells and 3 strains even had immunostimulating properties. The existence of significant correlation (r = -0.57; p < 0.01) between the immunomodulating activity of a strain and peripheral virulence of the virus for white mice indicates that the immunomodulation parameter may be used as another pathogenetic marker. This marker and that of the peripheral activity served the basis for creation, by means of the mathematical method of discrimination analysis, of a new pathogenetic characteristic--a single marker of strain virulence.", "contents": "[The degree of virulence in Far Eastern strains of the tick-borne encephalitis virus]. Screening of immunomodulating properties of 45 tick-borne encephalitis (TBE) virus strains isolated in the southern part of the Soviet Far East was carried out. TBE virus strains were found to have different effects on the immune responsiveness of host splenocytes. Over 90% of the strains isolated from hematothermals could inhibit the immune response of the host to a heterologous antigen (sheep erythrocytes); similar properties were found in 5 strains isolated from ticks. At the same time, most strains isolated from the vectors were unable to modulate the immune response of antibody-producing cells and 3 strains even had immunostimulating properties. The existence of significant correlation (r = -0.57; p < 0.01) between the immunomodulating activity of a strain and peripheral virulence of the virus for white mice indicates that the immunomodulation parameter may be used as another pathogenetic marker. This marker and that of the peripheral activity served the basis for creation, by means of the mathematical method of discrimination analysis, of a new pathogenetic characteristic--a single marker of strain virulence."} {"id": "PMID:1281951", "title": "[Simultaneous en-bloc allotransplantation of pancreas and kidney in the animal model. Comparison of separate organ and en-bloc pancreas/kidney transplantation in swine].", "content": "The high technical complication rate of pancreas transplantation requires large animal models to improve clinical transplant survival rates. The pig is a very suitable animal due to its anatomy, physiology and immunology which are similar to humans. In this study a model of en-bloc simultaneous pancreas and kidney transplantation was established which--in contrast to separate transplantation of both organs--decreases preservation time, operation time, and clamp time. Furthermore, the rates of intra- and postoperative complications were reduced compared with separate transplantation. The donor aorta (encompassing celiac axis, superior mesenteric artery, and left renal artery) is anastomosed en-bloc to the recipients aorta in a an oblique-to-side fashion. The portal vein is anastomosed end-to-side to the left common iliac vein. The exocrine pancreatic secretions are drained via duodenocystostomy to allow for monitoring of urinary amylase for rejection. The en-bloc technique is an alternative for pediatric donor organs since the risk of vascular complications is lower compared with separate implantation of the donor vessels. Based on our results in a large animal model the en-bloc technique could be used in adult uremic diabetic patients who receive a combined pancreas-kidney transplant from a pediatric cadaver donor.", "contents": "[Simultaneous en-bloc allotransplantation of pancreas and kidney in the animal model. Comparison of separate organ and en-bloc pancreas/kidney transplantation in swine]. The high technical complication rate of pancreas transplantation requires large animal models to improve clinical transplant survival rates. The pig is a very suitable animal due to its anatomy, physiology and immunology which are similar to humans. In this study a model of en-bloc simultaneous pancreas and kidney transplantation was established which--in contrast to separate transplantation of both organs--decreases preservation time, operation time, and clamp time. Furthermore, the rates of intra- and postoperative complications were reduced compared with separate transplantation. The donor aorta (encompassing celiac axis, superior mesenteric artery, and left renal artery) is anastomosed en-bloc to the recipients aorta in a an oblique-to-side fashion. The portal vein is anastomosed end-to-side to the left common iliac vein. The exocrine pancreatic secretions are drained via duodenocystostomy to allow for monitoring of urinary amylase for rejection. The en-bloc technique is an alternative for pediatric donor organs since the risk of vascular complications is lower compared with separate implantation of the donor vessels. Based on our results in a large animal model the en-bloc technique could be used in adult uremic diabetic patients who receive a combined pancreas-kidney transplant from a pediatric cadaver donor."} {"id": "PMID:1281952", "title": "Fibronectin production by chicken granulosa cells in vitro: effect of follicular development.", "content": "In vitro studies were conducted to investigate the role of chicken ovarian granulosa cells in the production of fibronectin, a component of the basal lamina of ovarian follicles. Collagenase dispersed granulosa cells obtained from the first (F1; about 35 mm in diameter) and third (F3; 15-20 mm in diameter) largest preovulatory follicles, as well as from a pool of small yellow follicles (SF; 6-10 mm in diameter), were incubated in serum-free medium-199 for 24 to 96 h in the absence and presence of luteinizing hormone (LH) or forskolin. Fibronectin secreted in the medium was quantitated by enzyme linked immunosorbent assay. Basal fibronectin production (which increased with the duration of incubation) was significantly greater (p < 0.001) in granulosa cells derived from mature follicle (F1) than in F3 or SF cells. Both LH and forskolin stimulated fibronectin production in SF and F3 cells in a dose-dependent manner; however, they were without effect in F1 cells. The magnitude of increase in fibronectin production elicited by LH or forskolin was greater in SF cells than in F3 cells. The cytoplasm of cultured granulosa cells taken at all stages of follicular development stained positively for fibronectin. These findings indicate that chicken granulosa cells produce fibronectin. This ability is acquired early in follicular development and the stimulatory effect of the gonadotropin (LH) diminished as the follicle approached ovulation.", "contents": "Fibronectin production by chicken granulosa cells in vitro: effect of follicular development. In vitro studies were conducted to investigate the role of chicken ovarian granulosa cells in the production of fibronectin, a component of the basal lamina of ovarian follicles. Collagenase dispersed granulosa cells obtained from the first (F1; about 35 mm in diameter) and third (F3; 15-20 mm in diameter) largest preovulatory follicles, as well as from a pool of small yellow follicles (SF; 6-10 mm in diameter), were incubated in serum-free medium-199 for 24 to 96 h in the absence and presence of luteinizing hormone (LH) or forskolin. Fibronectin secreted in the medium was quantitated by enzyme linked immunosorbent assay. Basal fibronectin production (which increased with the duration of incubation) was significantly greater (p < 0.001) in granulosa cells derived from mature follicle (F1) than in F3 or SF cells. Both LH and forskolin stimulated fibronectin production in SF and F3 cells in a dose-dependent manner; however, they were without effect in F1 cells. The magnitude of increase in fibronectin production elicited by LH or forskolin was greater in SF cells than in F3 cells. The cytoplasm of cultured granulosa cells taken at all stages of follicular development stained positively for fibronectin. These findings indicate that chicken granulosa cells produce fibronectin. This ability is acquired early in follicular development and the stimulatory effect of the gonadotropin (LH) diminished as the follicle approached ovulation."} {"id": "PMID:1281953", "title": "Immunocytochemistry of neurofibrillary tangles with antibodies to subregions of tau protein: identification of hidden and cleaved tau epitopes and a new phosphorylation site.", "content": "Antibodies to multiple epitopes spanning the length of the tau molecule were used to study Alzheimer neurofibrillary tangles (NFT) using immunocytochemical methods and several different methods of fixation and tissue processing, including staining of vibratome sections, hydrated autoclaving of paraffin sections and immunofluorescence of NFT isolated from fresh brain tissue. Smears and sections were pretreated with trypsin and/or phosphatase to further characterize antibody binding. In tissue fixed briefly in periodate-lysine-paraformaldehyde, tau immunoreactivity was detected in astrocytes, but only a few tau epitopes were detected in NFT with this fixation method. In contrast, all tau epitopes were detected in NFT in tissue fixed in formaldehyde for prolonged periods of time. In the hippocampus, the number of NFT detected in the dentate fascia was in proportion to the duration of dementia, as we previously noted. Dentate fascia NFT were intracellular (i-NFT) and were reactive with antibodies recognizing epitopes in both the carboxy- and amino-terminal regions of tau, but not the microtubule-binding domain of tau, suggesting that microtubule-binding domain epitopes are hidden in i-NFT. In contrast, NFT in the subiculum and layer II of the parahippocampal cortex were mostly extracellular (e-NFT), especially in severe cases of long duration. e-NFT were immunoreactive with antibodies to the microtubule-binding domain, but only weakly reactive with antibodies to carboxy- or amino-terminal epitopes, suggesting that e-NFT may contain fragments of tau. In both isolated NFT and NFT in sections, amino-terminal epitopes, including the Alz-50 epitope, were sensitive to trypsin proteolysis, which suggests that the lack of staining of e-NFT by antibodies to the amino-terminal regions of tau is due to proteolysis. Antibodies reactive with amino-terminal epitopes also stained fewer NFT following hydrated autoclaving, while those reacting with the carboxy half of tau stained more NFT after hydrated autoclaving. Thus, although carboxy-terminal regions are not detected in e-NFT, they are probably masked, rather than proteolytically cleaved, since they can be revealed by hydrated autoclaving. Finally, phosphatase treatment of isolated NFT revealed enhanced immunostaining not only with Tau-1, as in previous studies demonstrating abnormal phosphorylation of tau proteins in NFT, but also with an antibody to exon 2, which reveals yet another phosphorylation site in tau of NFT.", "contents": "Immunocytochemistry of neurofibrillary tangles with antibodies to subregions of tau protein: identification of hidden and cleaved tau epitopes and a new phosphorylation site. Antibodies to multiple epitopes spanning the length of the tau molecule were used to study Alzheimer neurofibrillary tangles (NFT) using immunocytochemical methods and several different methods of fixation and tissue processing, including staining of vibratome sections, hydrated autoclaving of paraffin sections and immunofluorescence of NFT isolated from fresh brain tissue. Smears and sections were pretreated with trypsin and/or phosphatase to further characterize antibody binding. In tissue fixed briefly in periodate-lysine-paraformaldehyde, tau immunoreactivity was detected in astrocytes, but only a few tau epitopes were detected in NFT with this fixation method. In contrast, all tau epitopes were detected in NFT in tissue fixed in formaldehyde for prolonged periods of time. In the hippocampus, the number of NFT detected in the dentate fascia was in proportion to the duration of dementia, as we previously noted. Dentate fascia NFT were intracellular (i-NFT) and were reactive with antibodies recognizing epitopes in both the carboxy- and amino-terminal regions of tau, but not the microtubule-binding domain of tau, suggesting that microtubule-binding domain epitopes are hidden in i-NFT. In contrast, NFT in the subiculum and layer II of the parahippocampal cortex were mostly extracellular (e-NFT), especially in severe cases of long duration. e-NFT were immunoreactive with antibodies to the microtubule-binding domain, but only weakly reactive with antibodies to carboxy- or amino-terminal epitopes, suggesting that e-NFT may contain fragments of tau. In both isolated NFT and NFT in sections, amino-terminal epitopes, including the Alz-50 epitope, were sensitive to trypsin proteolysis, which suggests that the lack of staining of e-NFT by antibodies to the amino-terminal regions of tau is due to proteolysis. Antibodies reactive with amino-terminal epitopes also stained fewer NFT following hydrated autoclaving, while those reacting with the carboxy half of tau stained more NFT after hydrated autoclaving. Thus, although carboxy-terminal regions are not detected in e-NFT, they are probably masked, rather than proteolytically cleaved, since they can be revealed by hydrated autoclaving. Finally, phosphatase treatment of isolated NFT revealed enhanced immunostaining not only with Tau-1, as in previous studies demonstrating abnormal phosphorylation of tau proteins in NFT, but also with an antibody to exon 2, which reveals yet another phosphorylation site in tau of NFT."} {"id": "PMID:1281954", "title": "Expression of leukocyte antigen CD34 by brain capillaries in Alzheimer's disease and neurologically normal subjects.", "content": "We studied the expression of a hemopoietic progenitor cell antigen, designated CD34, in brains from subjects with Alzheimer's disease (AD) and non-neurological controls. Immunoblots of brain microvessel proteins probed with monoclonal antibody QBEND/10 to the leukocyte antigen CD34 recognized a protein band with an apparent molecular mass of 90-100 kDa. Immunocytochemical staining of brain tissue sections showed CD34 to be expressed by all microvasculature including those of the circumventricular organs. In normal control brains such specific staining exhibited by QBEND/10 was indistinguishable from that obtained with collagen IV antibodies. In AD, however, increased vascular tendrils in form of endothelial abluminal processes and intraparenchymal abnormalities were evident in cortical and hippocampal regions, predominant in cases with severe pathology. Our results demonstrate that the leukocyte antigen CD34 is localized with the vascular endothelium throughout the human brain. These results also suggest that CD34 detects endothelial abnormalities in brains of AD subjects and support previous observations on the usefulness of CD34 to label abluminal microprocesses.", "contents": "Expression of leukocyte antigen CD34 by brain capillaries in Alzheimer's disease and neurologically normal subjects. We studied the expression of a hemopoietic progenitor cell antigen, designated CD34, in brains from subjects with Alzheimer's disease (AD) and non-neurological controls. Immunoblots of brain microvessel proteins probed with monoclonal antibody QBEND/10 to the leukocyte antigen CD34 recognized a protein band with an apparent molecular mass of 90-100 kDa. Immunocytochemical staining of brain tissue sections showed CD34 to be expressed by all microvasculature including those of the circumventricular organs. In normal control brains such specific staining exhibited by QBEND/10 was indistinguishable from that obtained with collagen IV antibodies. In AD, however, increased vascular tendrils in form of endothelial abluminal processes and intraparenchymal abnormalities were evident in cortical and hippocampal regions, predominant in cases with severe pathology. Our results demonstrate that the leukocyte antigen CD34 is localized with the vascular endothelium throughout the human brain. These results also suggest that CD34 detects endothelial abnormalities in brains of AD subjects and support previous observations on the usefulness of CD34 to label abluminal microprocesses."} {"id": "PMID:1281955", "title": "Intraventricular infusion of N-methyl-D-aspartate. 2. Acute neuronal consequences.", "content": "This study documents the ultrastructural features of acute neuronal injury following N-methyl-D-aspartate (NMDA) receptor activation. NMDA (100 nmol/microliters) or vehicle was infused over a 15-min period into the lateral ventricle of adult rats. After perfusion fixation, specimens demonstrating normal and abnormal patterns of vascular permeability to horseradish peroxidase were sampled for ultrastructural analysis. In NMDA-infused rats, brain regions exhibiting protein extravasation contained swollen dendritic profiles and abnormal neuronal perikarya. Although periventricular regions were most severely affected, parenchymal abnormalities were also detected in the cerebral cortex, septum, striatum, thalamus, hypothalamus and cerebellum. Mildly affected dendrites contained dark compact mitochondria, while in severely swollen dendrites mitochondria were enlarged with ruptured cristae. Focal sites of plasma membrane disruption were also detected within swollen dendrites. Swollen neurons commonly displayed peripheral pallor and increased numbers of cytoplasmic vacuoles. Other neurons appeared dark and shrunken, some containing disrupted mitochondria and pyknotic nuclei. Pretreatment with the NMDA antagonist MK-801 (2 mg/kg) attenuated the neuronal and dendritic alterations. In conditions where cerebrospinal fluid levels of glutamate are abnormally elevated, excessive NMDA receptor activation may lead to early vascular and neuronal complications which could work in concert to promote brain injury.", "contents": "Intraventricular infusion of N-methyl-D-aspartate. 2. Acute neuronal consequences. This study documents the ultrastructural features of acute neuronal injury following N-methyl-D-aspartate (NMDA) receptor activation. NMDA (100 nmol/microliters) or vehicle was infused over a 15-min period into the lateral ventricle of adult rats. After perfusion fixation, specimens demonstrating normal and abnormal patterns of vascular permeability to horseradish peroxidase were sampled for ultrastructural analysis. In NMDA-infused rats, brain regions exhibiting protein extravasation contained swollen dendritic profiles and abnormal neuronal perikarya. Although periventricular regions were most severely affected, parenchymal abnormalities were also detected in the cerebral cortex, septum, striatum, thalamus, hypothalamus and cerebellum. Mildly affected dendrites contained dark compact mitochondria, while in severely swollen dendrites mitochondria were enlarged with ruptured cristae. Focal sites of plasma membrane disruption were also detected within swollen dendrites. Swollen neurons commonly displayed peripheral pallor and increased numbers of cytoplasmic vacuoles. Other neurons appeared dark and shrunken, some containing disrupted mitochondria and pyknotic nuclei. Pretreatment with the NMDA antagonist MK-801 (2 mg/kg) attenuated the neuronal and dendritic alterations. In conditions where cerebrospinal fluid levels of glutamate are abnormally elevated, excessive NMDA receptor activation may lead to early vascular and neuronal complications which could work in concert to promote brain injury."} {"id": "PMID:1281956", "title": "Brain stem serotonin-synthesizing neurons in Alzheimer's disease: a clinicopathological correlation.", "content": "The location and number of brain stem serotonin-synthesizing neurons were analyzed in 11 patients with Alzheimer's disease (AD) and 5 age-matched controls using immunohistochemical techniques. In addition, the number of neuritic plaques and neurofibrillary tangles in the cortex and brain stem raphe was evaluated, as was the number of Nissl-stained raphe neurons. AD patients could be classified into two groups based on their raphe pathology; patients with such pathology (AD+) and those without (AD-). The number of large raphe neurons correlated significantly with the number of serotonin-synthesizing neurons in control material, indicating that all large neurons were serotonergic. This relationship was not apparent in AD+ patients, in whom the number of serotonin-synthesizing neurons correlated with the number of neurofibrillary tangles in the raphe of these patients. This indicates that in AD+ patients the serotonin-synthesizing neurons were selectively affected. There was no correlation between raphe and cortical pathology or raphe pathology and patient sex, age, mini-mental score or depression score, even when such scores were weighted for the interval between testing and death. There was a trend for the raphe pathology to correlate with the age of onset and duration of dementia and the Blessed dementia score in AD+ patients. Most AD+ patients with severe raphe lesions had clinical dementia only, while AD- patients had additional clinical features. The raphe lesions were more dramatic in AD+ patients with a rapid progression of symptoms.", "contents": "Brain stem serotonin-synthesizing neurons in Alzheimer's disease: a clinicopathological correlation. The location and number of brain stem serotonin-synthesizing neurons were analyzed in 11 patients with Alzheimer's disease (AD) and 5 age-matched controls using immunohistochemical techniques. In addition, the number of neuritic plaques and neurofibrillary tangles in the cortex and brain stem raphe was evaluated, as was the number of Nissl-stained raphe neurons. AD patients could be classified into two groups based on their raphe pathology; patients with such pathology (AD+) and those without (AD-). The number of large raphe neurons correlated significantly with the number of serotonin-synthesizing neurons in control material, indicating that all large neurons were serotonergic. This relationship was not apparent in AD+ patients, in whom the number of serotonin-synthesizing neurons correlated with the number of neurofibrillary tangles in the raphe of these patients. This indicates that in AD+ patients the serotonin-synthesizing neurons were selectively affected. There was no correlation between raphe and cortical pathology or raphe pathology and patient sex, age, mini-mental score or depression score, even when such scores were weighted for the interval between testing and death. There was a trend for the raphe pathology to correlate with the age of onset and duration of dementia and the Blessed dementia score in AD+ patients. Most AD+ patients with severe raphe lesions had clinical dementia only, while AD- patients had additional clinical features. The raphe lesions were more dramatic in AD+ patients with a rapid progression of symptoms."} {"id": "PMID:1281957", "title": "Diagnostic criteria for human diffuse malignant mesothelioma.", "content": "Diffuse malignant mesothelioma is a rare tumor in the general population, yet is unique in that it is caused almost exclusively by exposure to asbestos with long-term latency (15 years and over). Pathologists are required to provide a reliable diagnosis of the tumor for clinicians who are responsible for the treatment of affected patients. Pathological diagnosis of diffuse malignant mesothelioma is not always easy; however, it has improved over the last few decades. Currently, comprehensive analysis, including gross appearance, histology, histochemistry, immunocytochemistry and electron microscopy is recommended as the best approach to an accurate diagnosis of diffuse malignant mesothelioma.", "contents": "Diagnostic criteria for human diffuse malignant mesothelioma. Diffuse malignant mesothelioma is a rare tumor in the general population, yet is unique in that it is caused almost exclusively by exposure to asbestos with long-term latency (15 years and over). Pathologists are required to provide a reliable diagnosis of the tumor for clinicians who are responsible for the treatment of affected patients. Pathological diagnosis of diffuse malignant mesothelioma is not always easy; however, it has improved over the last few decades. Currently, comprehensive analysis, including gross appearance, histology, histochemistry, immunocytochemistry and electron microscopy is recommended as the best approach to an accurate diagnosis of diffuse malignant mesothelioma."} {"id": "PMID:1281958", "title": "Epitopic heterogeneity of the CD36 antigen expressed by normal and neoplastic endothelial cells. An immunohistochemical study with a novel monoclonal antibody 8C9.", "content": "Phenotypic and functional heterogeneity of endothelial cells (ECs) is being recognized with increasing frequency. Here we report a novel murine monoclonal antibody (MoAb), named 8C9, that detects a unique epitope on the leukocyte differentiation antigen CD36 (platelet glycoprotein IV or IIIb) expressed by both normal and neoplastic ECs. In immunohistochemical and flow-cytometric studies, 8C9-immunoreactivity was detected on capillary ECs, adipocytes, monocytes, platelets and a human monocytoid cell line U-937, which are known to express the CD36 antigen. Blocking experiments using U-937 cells and studies on cryostat sections revealed that a murine MoAb OKM5, which detects the CD36 antigen, blocked the binding of 8C9 to its antigen. Immunoblot analysis showed that 8C9 bound to a 97-kDa membrane protein expressed by U-937 cells treated with phorbol ester. These results indicate that 8C9 detects the CD36 antigen. However, the findings that some OKM5-positive normal ECs in the liver, spleen and lymph nodes as well as neoplastic ECs in a cutaneous angiosarcoma did not react with 8C9, together with the fact that the CD36 antigen does not form a complex or associate with other proteins, suggest epitopic heterogeneity of the CD36 antigen expressed by these tissues.", "contents": "Epitopic heterogeneity of the CD36 antigen expressed by normal and neoplastic endothelial cells. An immunohistochemical study with a novel monoclonal antibody 8C9. Phenotypic and functional heterogeneity of endothelial cells (ECs) is being recognized with increasing frequency. Here we report a novel murine monoclonal antibody (MoAb), named 8C9, that detects a unique epitope on the leukocyte differentiation antigen CD36 (platelet glycoprotein IV or IIIb) expressed by both normal and neoplastic ECs. In immunohistochemical and flow-cytometric studies, 8C9-immunoreactivity was detected on capillary ECs, adipocytes, monocytes, platelets and a human monocytoid cell line U-937, which are known to express the CD36 antigen. Blocking experiments using U-937 cells and studies on cryostat sections revealed that a murine MoAb OKM5, which detects the CD36 antigen, blocked the binding of 8C9 to its antigen. Immunoblot analysis showed that 8C9 bound to a 97-kDa membrane protein expressed by U-937 cells treated with phorbol ester. These results indicate that 8C9 detects the CD36 antigen. However, the findings that some OKM5-positive normal ECs in the liver, spleen and lymph nodes as well as neoplastic ECs in a cutaneous angiosarcoma did not react with 8C9, together with the fact that the CD36 antigen does not form a complex or associate with other proteins, suggest epitopic heterogeneity of the CD36 antigen expressed by these tissues."} {"id": "PMID:1281959", "title": "Immune disorders in depression: higher T helper/T suppressor-cytotoxic cell ratio.", "content": "This study investigated the leukocyte T helper and T suppressor-cytotoxic cell (sub)set profile of minor, simple major and melancholic depressives versus normal controls. Using both monoclonal antibody staining and flow cytometry, we determined the absolute numbers and percentages of the following T cell immune subsets: T helper (CD4+), T virgin (CD4+CD45+), T memory (CD4+CD45-), T suppressor/cytotoxic (CD8+), CD8+ T suppressor (CD8+CD57-) and CD8+ T cytotoxic (CD8+CD57+) cells. After computing the CD4+/CD8+ ratio, we detected a significantly increased ratio in depressed patients as compared with healthy controls. Depression per se is characterized by a higher percentage of CD4+ and a lower percentage of CD8+CD57- cells. Melancholic depressed subjects exhibit a significantly increased number of CD4+ and CD4+CD45- cells. The combined use of various percentages of CD4+ and CD8+ (sub)sets yields a high degree of marker positivity for melancholia: through cumulative evaluation of those percentages, the marker positivity increases to 68% (sensitivity) and the specificity is 95%. These results together with our previous reports may refer to a depression-related state of T cell activation.", "contents": "Immune disorders in depression: higher T helper/T suppressor-cytotoxic cell ratio. This study investigated the leukocyte T helper and T suppressor-cytotoxic cell (sub)set profile of minor, simple major and melancholic depressives versus normal controls. Using both monoclonal antibody staining and flow cytometry, we determined the absolute numbers and percentages of the following T cell immune subsets: T helper (CD4+), T virgin (CD4+CD45+), T memory (CD4+CD45-), T suppressor/cytotoxic (CD8+), CD8+ T suppressor (CD8+CD57-) and CD8+ T cytotoxic (CD8+CD57+) cells. After computing the CD4+/CD8+ ratio, we detected a significantly increased ratio in depressed patients as compared with healthy controls. Depression per se is characterized by a higher percentage of CD4+ and a lower percentage of CD8+CD57- cells. Melancholic depressed subjects exhibit a significantly increased number of CD4+ and CD4+CD45- cells. The combined use of various percentages of CD4+ and CD8+ (sub)sets yields a high degree of marker positivity for melancholia: through cumulative evaluation of those percentages, the marker positivity increases to 68% (sensitivity) and the specificity is 95%. These results together with our previous reports may refer to a depression-related state of T cell activation."} {"id": "PMID:1281960", "title": "The Swedish version of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Construct validity and interrater reliability.", "content": "The Positive and Negative Syndrome Scale (PANSS) has been translated into Swedish and tested in 88 chronic schizophrenic patients. All 4 subscales exhibited a roughly normal distribution. The overall alpha for the positive, negative and general psychopathology subscales were 0.81, 0.58 and 0.63, respectively. The correlation between the positive and negative subscales was -0.17 (NS). The interrater reliability was 0.73-0.75 for the positive, 0.65-0.74 for the negative and 0.75-0.77 for the general psychopathology subscales. The intraclass coefficients were 0.75-0.77 for the positive, 0.27-0.46 for the negative, 0.56-0.72 for the general psychopathology subscales and 0.66-0.71 for the total scale. Thus, the validity and reliability of the PANSS (Swedish version) are quite satisfactory.", "contents": "The Swedish version of the Positive and Negative Syndrome Scale (PANSS) for schizophrenia. Construct validity and interrater reliability. The Positive and Negative Syndrome Scale (PANSS) has been translated into Swedish and tested in 88 chronic schizophrenic patients. All 4 subscales exhibited a roughly normal distribution. The overall alpha for the positive, negative and general psychopathology subscales were 0.81, 0.58 and 0.63, respectively. The correlation between the positive and negative subscales was -0.17 (NS). The interrater reliability was 0.73-0.75 for the positive, 0.65-0.74 for the negative and 0.75-0.77 for the general psychopathology subscales. The intraclass coefficients were 0.75-0.77 for the positive, 0.27-0.46 for the negative, 0.56-0.72 for the general psychopathology subscales and 0.66-0.71 for the total scale. Thus, the validity and reliability of the PANSS (Swedish version) are quite satisfactory."} {"id": "PMID:1281961", "title": "Assessment of the clinical value of urinary trypsin inhibitory activity in elderly people.", "content": "To assess the clinical value of urinary trypsin inhibitory activity (UTIA) in elderly people, a prospective study was carried out over 4 months in our internal medicine department. Two hundred and forty-three patients of more than 60 years of age were included. A positive correlation was observed between UTIA and serum creatinine (p < 10(-3)). In the population with serum creatinine of less than 133 mumol/l (200 patients), UTIA was independent of age, sex and serum creatinine. UTIA was compared with seven serum inflammatory proteins titrated on patient admission. The principal interest of UTIA determination appeared in bacterial infections. UTIA was significantly increased in this group (p < 10(-4)). However, a positive correlation was proved only with C-reactive protein (CRP) (p = 9 x 10(-4)). Nevertheless, CRP appeared to be the best marker of bacterial infectious diseases after receiver operating characteristic curves analysis.", "contents": "Assessment of the clinical value of urinary trypsin inhibitory activity in elderly people. To assess the clinical value of urinary trypsin inhibitory activity (UTIA) in elderly people, a prospective study was carried out over 4 months in our internal medicine department. Two hundred and forty-three patients of more than 60 years of age were included. A positive correlation was observed between UTIA and serum creatinine (p < 10(-3)). In the population with serum creatinine of less than 133 mumol/l (200 patients), UTIA was independent of age, sex and serum creatinine. UTIA was compared with seven serum inflammatory proteins titrated on patient admission. The principal interest of UTIA determination appeared in bacterial infections. UTIA was significantly increased in this group (p < 10(-4)). However, a positive correlation was proved only with C-reactive protein (CRP) (p = 9 x 10(-4)). Nevertheless, CRP appeared to be the best marker of bacterial infectious diseases after receiver operating characteristic curves analysis."} {"id": "PMID:1281962", "title": "Time engaged in reading. A critical factor in reading achievement.", "content": "The reading achievement of deaf children may be low not only as a result of factors related to the hearing loss, such as a lag in language development. Environmental factors such as the quantity and quality of reading instruction, for example, may also cause low reading achievement. This study looked at the amount of time spent reading and the types of teacher interactions during reading instruction in classrooms at a school for deaf children and associated satellite classes in New Zealand. It was found that the deaf children spent very low levels of time engaged in reading and were subjected to teacher interactions that may inhibit the development of meaning-based reading skills. The quantity and quality of reading instruction for deaf children may differ from that experienced by most hearing children in New Zealand.", "contents": "Time engaged in reading. A critical factor in reading achievement. The reading achievement of deaf children may be low not only as a result of factors related to the hearing loss, such as a lag in language development. Environmental factors such as the quantity and quality of reading instruction, for example, may also cause low reading achievement. This study looked at the amount of time spent reading and the types of teacher interactions during reading instruction in classrooms at a school for deaf children and associated satellite classes in New Zealand. It was found that the deaf children spent very low levels of time engaged in reading and were subjected to teacher interactions that may inhibit the development of meaning-based reading skills. The quantity and quality of reading instruction for deaf children may differ from that experienced by most hearing children in New Zealand."} {"id": "PMID:1281963", "title": "Study of the activities of Chinese herb Viscum alniformosanae Part II: The components of conditioned medium produced by Viscum alniformosanae-stimulated mononuclear cells.", "content": "The human promyelocytic cell line HL-60 can be induced to monocytoid terminal differentiation by several conditioned media produced by lectin-stimulated mononuclear cells. We reported previously that a 572-conditioned medium (CM) secreted from viscum alniformosanae-stimulated mononuclear cells also had the capacity of inducing HL-60 leukemic cells into mature monocytes. In the present study, we showed that 572-CM did not contain IFN-r, TNF, IL-1 and IL-2 as determined by using ELISA tests. This CM was unable to induce granulocyte-macrophage colony formation. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was used to detect the components of this CM. After running the acrylamide gels, a wide band protein, in the 65-80 kd range was obtained and it was different from those of other mitogens.", "contents": "Study of the activities of Chinese herb Viscum alniformosanae Part II: The components of conditioned medium produced by Viscum alniformosanae-stimulated mononuclear cells. The human promyelocytic cell line HL-60 can be induced to monocytoid terminal differentiation by several conditioned media produced by lectin-stimulated mononuclear cells. We reported previously that a 572-conditioned medium (CM) secreted from viscum alniformosanae-stimulated mononuclear cells also had the capacity of inducing HL-60 leukemic cells into mature monocytes. In the present study, we showed that 572-CM did not contain IFN-r, TNF, IL-1 and IL-2 as determined by using ELISA tests. This CM was unable to induce granulocyte-macrophage colony formation. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was used to detect the components of this CM. After running the acrylamide gels, a wide band protein, in the 65-80 kd range was obtained and it was different from those of other mitogens."} {"id": "PMID:1281964", "title": "Prediction of pregnancy outcome with single versus serial maternal serum alpha-fetoprotein tests.", "content": "The purpose of our study was to determine whether the trend of three maternal serum alpha-fetoprotein samples was more predictive of pregnancy outcome than the initial sample in the evaluation of patients with unexplained alpha-fetoprotein elevations. A total of 432 patients with unexplained elevation of their first two maternal serum alpha-fetoprotein samples had a third sample drawn. Pregnancy outcomes were determined. Patients were grouped for analysis according to the level of the initial sample, the final sample, and the trend of three samples. Statistical analysis was by chi 2 and logistic regression, with p < 0.05 considered significant. The initial maternal serum alpha-fetoprotein was most predictive of preterm delivery (p < 0.001), size small for gestational age (p < 0.001), and intrauterine fetal death (p = 0.009). Neither the final value nor the trend of three values was as prognostic. The first maternal serum alpha-fetoprotein is the best predictor of pregnancy outcome. Obtaining a second sample to confirm the elevation is appropriate, but additional samples provide minimal information.", "contents": "Prediction of pregnancy outcome with single versus serial maternal serum alpha-fetoprotein tests. The purpose of our study was to determine whether the trend of three maternal serum alpha-fetoprotein samples was more predictive of pregnancy outcome than the initial sample in the evaluation of patients with unexplained alpha-fetoprotein elevations. A total of 432 patients with unexplained elevation of their first two maternal serum alpha-fetoprotein samples had a third sample drawn. Pregnancy outcomes were determined. Patients were grouped for analysis according to the level of the initial sample, the final sample, and the trend of three samples. Statistical analysis was by chi 2 and logistic regression, with p < 0.05 considered significant. The initial maternal serum alpha-fetoprotein was most predictive of preterm delivery (p < 0.001), size small for gestational age (p < 0.001), and intrauterine fetal death (p = 0.009). Neither the final value nor the trend of three values was as prognostic. The first maternal serum alpha-fetoprotein is the best predictor of pregnancy outcome. Obtaining a second sample to confirm the elevation is appropriate, but additional samples provide minimal information."} {"id": "PMID:1281966", "title": "Western blot analysis of antibodies to Leishmania infantum antigens: potential of the 14-kD and 16-kD antigens for diagnosis and epidemiologic purposes.", "content": "When infected with Leishmania species, patients develop specific antibodies that constitute the basis of serodiagnosis. Using Western blot analysis, we studied the specificity of anti-L. infantum antibodies in patients with visceral leishmaniasis (including patients with acquired immunodeficiency syndrome [AIDS]) and in healthy subjects living in an endemic area. Sera from patients with visceral leishmaniasis recognized numerous antigens that had a molecular mass range of 12-120 kD. The 14-, 16-, 28-30-, 46-, and 68-kD antigens were recognized by 92%, 95%, 63%, 80%, 69%, and 89% of the patients' sera, respectively. The 14-16-kD antigens had the greatest specificity for leishmaniasis. The same pattern was found with sera from AIDS patients with proven leishmaniasis, but the 14-kD band was not present in some cases; recognition of the 16-kD band was constant. In these patients, Western blotting characterized specific antibodies even when the results of classic serologic tests (indirect immunofluorescent antibody test and enzyme-linked immunosorbent assay) were negative. Western blotting was found to be more sensitive than the IFA and ELISA, and it was used to detect antibodies to the 14-, 16-, 22-, and 24-kD antigens in subjects living in an endemic area. The detection of antibodies for the 14-kD and 16-kD Leishmania antigens would be a valuable tool both in the diagnosis of visceral leishmaniasis and in epidemiologic studies.", "contents": "Western blot analysis of antibodies to Leishmania infantum antigens: potential of the 14-kD and 16-kD antigens for diagnosis and epidemiologic purposes. When infected with Leishmania species, patients develop specific antibodies that constitute the basis of serodiagnosis. Using Western blot analysis, we studied the specificity of anti-L. infantum antibodies in patients with visceral leishmaniasis (including patients with acquired immunodeficiency syndrome [AIDS]) and in healthy subjects living in an endemic area. Sera from patients with visceral leishmaniasis recognized numerous antigens that had a molecular mass range of 12-120 kD. The 14-, 16-, 28-30-, 46-, and 68-kD antigens were recognized by 92%, 95%, 63%, 80%, 69%, and 89% of the patients' sera, respectively. The 14-16-kD antigens had the greatest specificity for leishmaniasis. The same pattern was found with sera from AIDS patients with proven leishmaniasis, but the 14-kD band was not present in some cases; recognition of the 16-kD band was constant. In these patients, Western blotting characterized specific antibodies even when the results of classic serologic tests (indirect immunofluorescent antibody test and enzyme-linked immunosorbent assay) were negative. Western blotting was found to be more sensitive than the IFA and ELISA, and it was used to detect antibodies to the 14-, 16-, 22-, and 24-kD antigens in subjects living in an endemic area. The detection of antibodies for the 14-kD and 16-kD Leishmania antigens would be a valuable tool both in the diagnosis of visceral leishmaniasis and in epidemiologic studies."} {"id": "PMID:1281967", "title": "Rapid diagnosis of Bancroftian filariasis by acridine orange staining of centrifuged parasites.", "content": "A rapid diagnostic test for detection of microfilaremia using a microhematocrit tube precoated with acridine orange (the Quantitative Buffy Coat [QBC] tube) was compared with a conventional 50 microliters-thick blood film (TF) in 119 volunteers in an area of Recife, Brazil that was endemic for Wuchereria bancrofti. Both the QBC and the TF techniques were 100% specific, and thus positive predictive values were equal at 100% for each technique in all subjects studied. Both techniques had equal negative predictive values of 100% in subjects with microfilarial counts > 100 per milliliter (mf/ml). Counts < 20 mf/ml are below a cutoff equal to the calculated limit of sensitivity of each of the two techniques. For those individuals with counts between 20 and 99 mf/ml, negative predictive values were, for practical diagnostic purposes, equivalent at 97.5% for the QBC technique and 99.0% for the TF. Because the QBC technique has predictive values as high as conventional TF, the convenience and rapidity of the technique will make the QBC technique a desirable alternative diagnostic method in those clinical settings where the equipment is available. A positive result will be available in less than six min after obtaining the specimen in individuals with counts < 100 mf/ml, and individuals with lower or no microfilaremia will have a result within 6-12 min.", "contents": "Rapid diagnosis of Bancroftian filariasis by acridine orange staining of centrifuged parasites. A rapid diagnostic test for detection of microfilaremia using a microhematocrit tube precoated with acridine orange (the Quantitative Buffy Coat [QBC] tube) was compared with a conventional 50 microliters-thick blood film (TF) in 119 volunteers in an area of Recife, Brazil that was endemic for Wuchereria bancrofti. Both the QBC and the TF techniques were 100% specific, and thus positive predictive values were equal at 100% for each technique in all subjects studied. Both techniques had equal negative predictive values of 100% in subjects with microfilarial counts > 100 per milliliter (mf/ml). Counts < 20 mf/ml are below a cutoff equal to the calculated limit of sensitivity of each of the two techniques. For those individuals with counts between 20 and 99 mf/ml, negative predictive values were, for practical diagnostic purposes, equivalent at 97.5% for the QBC technique and 99.0% for the TF. Because the QBC technique has predictive values as high as conventional TF, the convenience and rapidity of the technique will make the QBC technique a desirable alternative diagnostic method in those clinical settings where the equipment is available. A positive result will be available in less than six min after obtaining the specimen in individuals with counts < 100 mf/ml, and individuals with lower or no microfilaremia will have a result within 6-12 min."} {"id": "PMID:1281968", "title": "Diversity in the immunodominant determinants of the circumsporozoite protein of Plasmodium falciparum parasites from malaria-endemic regions of Papua New Guinea and Brazil.", "content": "To determine the nature and extent of variation in the T cell sites of the Plasmodium falciparum circumsporozoite (CS) protein, a candidate antigen in the development of a malaria vaccine, we cloned and sequenced 69 recombinant clones of the CS protein gene representing 18 and 17 P. falciparum isolates from infected individuals from Madang, Papua New Guinea (PNG), a holoendemic malaria region, and Paragaminos and Jacunda, Brazil, relatively low endemic regions, respectively. As previously known, the amino acid sequence polymorphism was restricted to the three immunodominant regions of the protein, Th1R-N1, Th2R, and Th3R. While some of the observed nonsilent mutations in the T cell determinants of the CS protein were similar to those previously identified, we have found new amino acid changes in each of the polymorphic sequences in parasites from PNG and Brazil. A comparison of the CS epitope sequences of parasites from PNG and Brazil with the previously known CS epitope sequences of parasites from Brazil and The Gambia showed the following: 1) polymorphism was found in the Th1R-N1, Th2R, and Th3R region; however, while amino acid substitutions in the Th1R-N1 and Th2R region tended to be conservative, the substitutions found in the Th3R region were not, suggesting that the Th3R epitope may be rapidly evolving to allow parasites to escape host antiparasite cytotoxic T cell-enforced immune responses, and 2) the CS proteins of P. falciparum from high malaria-transmission regions (PNG and The Gambia) appear more polymorphic than the CS proteins of parasites from relatively low malaria-endemic regions in Brazil, where P. falciparum infection has been recently established.", "contents": "Diversity in the immunodominant determinants of the circumsporozoite protein of Plasmodium falciparum parasites from malaria-endemic regions of Papua New Guinea and Brazil. To determine the nature and extent of variation in the T cell sites of the Plasmodium falciparum circumsporozoite (CS) protein, a candidate antigen in the development of a malaria vaccine, we cloned and sequenced 69 recombinant clones of the CS protein gene representing 18 and 17 P. falciparum isolates from infected individuals from Madang, Papua New Guinea (PNG), a holoendemic malaria region, and Paragaminos and Jacunda, Brazil, relatively low endemic regions, respectively. As previously known, the amino acid sequence polymorphism was restricted to the three immunodominant regions of the protein, Th1R-N1, Th2R, and Th3R. While some of the observed nonsilent mutations in the T cell determinants of the CS protein were similar to those previously identified, we have found new amino acid changes in each of the polymorphic sequences in parasites from PNG and Brazil. A comparison of the CS epitope sequences of parasites from PNG and Brazil with the previously known CS epitope sequences of parasites from Brazil and The Gambia showed the following: 1) polymorphism was found in the Th1R-N1, Th2R, and Th3R region; however, while amino acid substitutions in the Th1R-N1 and Th2R region tended to be conservative, the substitutions found in the Th3R region were not, suggesting that the Th3R epitope may be rapidly evolving to allow parasites to escape host antiparasite cytotoxic T cell-enforced immune responses, and 2) the CS proteins of P. falciparum from high malaria-transmission regions (PNG and The Gambia) appear more polymorphic than the CS proteins of parasites from relatively low malaria-endemic regions in Brazil, where P. falciparum infection has been recently established."} {"id": "PMID:1281969", "title": "Comparative light-microscopic and immunohistochemical study of traumatic and palisaded encapsulated neuromas of the skin.", "content": "The primary hyperplastic nature of palisaded encapsulated neuromas (PENs) has been recently challenged by suggesting a traumatic origin. We studied eight cases of traumatic neuroma (TN) and 12 cases of PEN by routine light-microscopic, histochemical, and immunohistochemical methods to assess evidence of previous tissue injury. Sections from the formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin, trichrome, elastic, reticulin, Giemsa, colloidal iron (with and without hyaluronidase), and Bielschowsky silver stains. Antibodies were applied to collagen types I, III, and IV, MAC 387, factor XIIIa, alpha 1-antitrypsin (A1AT), epithelial membrane antigen (EMA), Leu-7, and myelin basic protein using ABC techniques. We found that (a) in TN the individual fascicles were usually surrounded by perineurial cells, whereas in PEN the perineurial cells were observed mainly in the capsular areas and only rarely within the fascicles as evidenced by EMA antibodies; (b) histochemically TN contained considerably larger amounts of collagen (types I and III), acidic mucin, and myelin products than did PEN; and (c) neither PEN nor TN contained increased inflammatory cells or cells positive for factor XIIIa, MAC 387, or A1AT. We conclude that (a) there are substantial structural and histochemical differences between TN and PEN, (b) the changes suggest that the classic form of PEN has a different histogenesis than TN, and (c) on histologic grounds, chronic minor trauma could not be excluded as an etiologic factor for PEN.", "contents": "Comparative light-microscopic and immunohistochemical study of traumatic and palisaded encapsulated neuromas of the skin. The primary hyperplastic nature of palisaded encapsulated neuromas (PENs) has been recently challenged by suggesting a traumatic origin. We studied eight cases of traumatic neuroma (TN) and 12 cases of PEN by routine light-microscopic, histochemical, and immunohistochemical methods to assess evidence of previous tissue injury. Sections from the formalin-fixed, paraffin-embedded tissue were stained with hematoxylin-eosin, trichrome, elastic, reticulin, Giemsa, colloidal iron (with and without hyaluronidase), and Bielschowsky silver stains. Antibodies were applied to collagen types I, III, and IV, MAC 387, factor XIIIa, alpha 1-antitrypsin (A1AT), epithelial membrane antigen (EMA), Leu-7, and myelin basic protein using ABC techniques. We found that (a) in TN the individual fascicles were usually surrounded by perineurial cells, whereas in PEN the perineurial cells were observed mainly in the capsular areas and only rarely within the fascicles as evidenced by EMA antibodies; (b) histochemically TN contained considerably larger amounts of collagen (types I and III), acidic mucin, and myelin products than did PEN; and (c) neither PEN nor TN contained increased inflammatory cells or cells positive for factor XIIIa, MAC 387, or A1AT. We conclude that (a) there are substantial structural and histochemical differences between TN and PEN, (b) the changes suggest that the classic form of PEN has a different histogenesis than TN, and (c) on histologic grounds, chronic minor trauma could not be excluded as an etiologic factor for PEN."} {"id": "PMID:1281970", "title": "Reevaluation of host corneal tissue 1955 to 1970: Calcofluor white staining for occult acanthamoebic infection.", "content": "The incidence of acanthamoebic keratitis before 1974 is not known. A retrospective study was conducted to understand better the early epidemiology of this infection. Host corneal tissue from therapeutic penetrating keratoplasties submitted to the Stanford Eye Pathology Laboratory from 1955 to 1970 were stained with Calcofluor white and observed by fluorescence microscopy. We reviewed 197 cases, and no misdiagnosed cases of acanthamoebic infection were found.", "contents": "Reevaluation of host corneal tissue 1955 to 1970: Calcofluor white staining for occult acanthamoebic infection. The incidence of acanthamoebic keratitis before 1974 is not known. A retrospective study was conducted to understand better the early epidemiology of this infection. Host corneal tissue from therapeutic penetrating keratoplasties submitted to the Stanford Eye Pathology Laboratory from 1955 to 1970 were stained with Calcofluor white and observed by fluorescence microscopy. We reviewed 197 cases, and no misdiagnosed cases of acanthamoebic infection were found."} {"id": "PMID:1281971", "title": "Relative sparing of nitric oxide synthase-containing neurons in the hippocampal formation in Alzheimer's disease.", "content": "Nitric oxide (NO) is an endogenous neuromodulator that may mediate neurotoxic effects of glutamate. NO-synthesizing neurons are, however, resistant to NO- and glutamate-induced neurotoxicity. We now show that NO synthase neurons are selectively spared in patients with Alzheimer's disease, even in a severely affected region of the brain such as the hippocampal formation.", "contents": "Relative sparing of nitric oxide synthase-containing neurons in the hippocampal formation in Alzheimer's disease. Nitric oxide (NO) is an endogenous neuromodulator that may mediate neurotoxic effects of glutamate. NO-synthesizing neurons are, however, resistant to NO- and glutamate-induced neurotoxicity. We now show that NO synthase neurons are selectively spared in patients with Alzheimer's disease, even in a severely affected region of the brain such as the hippocampal formation."} {"id": "PMID:1281972", "title": "Delayed surgery for congenital diaphragmatic hernia: neurodevelopmental outcome in later childhood.", "content": "The long term neurodevelopmental outcome was assessed in 23 survivors born with congenital diaphragmatic hernia who had been managed by an elective delay in surgical repair after a period of stabilisation. This cohort was treated in one neonatal surgical unit between 1983 and 1989 by a single team of surgeons and anaesthetists. All children underwent comprehensive neurological, developmental, and anthropometric assessment at a mean age of 56 (range 18-94) months. Two children (9%) had major disability (one with hemiplegia and one with a lower limb monoplegia) and two further children had minor disabilities (one had partial sightedness and squint, the other squint only). The mean developmental quotient (DQ) for the group was 108 (SD 10.8) and none had developmental delay (defined as DQ < 70). Infants who had spent more time in hospital, or had had a longer duration of ventilation, tended to have lower weights and lower occipitofrontal circumference centiles in later childhood. Preoperative stabilisation and delayed surgery for congenital diaphragmatic hernia is not associated with an impaired neurodevelopmental outcome.", "contents": "Delayed surgery for congenital diaphragmatic hernia: neurodevelopmental outcome in later childhood. The long term neurodevelopmental outcome was assessed in 23 survivors born with congenital diaphragmatic hernia who had been managed by an elective delay in surgical repair after a period of stabilisation. This cohort was treated in one neonatal surgical unit between 1983 and 1989 by a single team of surgeons and anaesthetists. All children underwent comprehensive neurological, developmental, and anthropometric assessment at a mean age of 56 (range 18-94) months. Two children (9%) had major disability (one with hemiplegia and one with a lower limb monoplegia) and two further children had minor disabilities (one had partial sightedness and squint, the other squint only). The mean developmental quotient (DQ) for the group was 108 (SD 10.8) and none had developmental delay (defined as DQ < 70). Infants who had spent more time in hospital, or had had a longer duration of ventilation, tended to have lower weights and lower occipitofrontal circumference centiles in later childhood. Preoperative stabilisation and delayed surgery for congenital diaphragmatic hernia is not associated with an impaired neurodevelopmental outcome."} {"id": "PMID:1281973", "title": "Effect of hypothermia on pancreatic acinar cells in rats.", "content": "This study was designed to evaluate the effects of direct pancreatic surface cooling on the exocrine pancreas. We measured the changes in serum amylase levels, pancreatic water, amylase and cathepsin B as a lysosomal enzyme, content, histological changes of acinar cells, and the subcellular distribution of cathepsin B after 1-2- and 3-hours of direct pancreatic cooling in rats. In addition, we evaluated the in-vivo amylase and cathepsin B output stimulated by caerulein, in-vitro lysosomal and mitochondrial fragility as well as the pancreatic adenylate energy metabolism. 2-hours cooling showed slight yet significant changes, but 3-hours cooling caused most significant changes including hyperamylasemia, increased pancreatic amylase content and very mild histological changes. Furthermore, 3-hours cooling caused a remarkable redistribution of cathepsin B activity from the lysosomal fraction to the heavier zymogen fraction, and colocalization of the lysosomal enzyme with the digestive enzyme, the impaired amylase and cathepsin B output into pancreatic juice stimulated by caerulein as well as the accelerated fragility of lysosomes and mitochondria, and impaired pancreatic adenylate energy metabolism. These results indicate the impaired exocrine pancreatic functions induced by direct pancreatic cooling injury induced by cooling as shown in the other models of experimental pancreatitis. Moreover, this cooling model of pancreatitis seems to be useful in understanding the early events in the pathogenesis of acute pancreatitis, and we must take these \"cold\" injuries of exocrine pancreas into considerations, particularly in the pancreas transplantation and in other major abdominal surgeries where the pancreas is exposed to cooling.", "contents": "Effect of hypothermia on pancreatic acinar cells in rats. This study was designed to evaluate the effects of direct pancreatic surface cooling on the exocrine pancreas. We measured the changes in serum amylase levels, pancreatic water, amylase and cathepsin B as a lysosomal enzyme, content, histological changes of acinar cells, and the subcellular distribution of cathepsin B after 1-2- and 3-hours of direct pancreatic cooling in rats. In addition, we evaluated the in-vivo amylase and cathepsin B output stimulated by caerulein, in-vitro lysosomal and mitochondrial fragility as well as the pancreatic adenylate energy metabolism. 2-hours cooling showed slight yet significant changes, but 3-hours cooling caused most significant changes including hyperamylasemia, increased pancreatic amylase content and very mild histological changes. Furthermore, 3-hours cooling caused a remarkable redistribution of cathepsin B activity from the lysosomal fraction to the heavier zymogen fraction, and colocalization of the lysosomal enzyme with the digestive enzyme, the impaired amylase and cathepsin B output into pancreatic juice stimulated by caerulein as well as the accelerated fragility of lysosomes and mitochondria, and impaired pancreatic adenylate energy metabolism. These results indicate the impaired exocrine pancreatic functions induced by direct pancreatic cooling injury induced by cooling as shown in the other models of experimental pancreatitis. Moreover, this cooling model of pancreatitis seems to be useful in understanding the early events in the pathogenesis of acute pancreatitis, and we must take these \"cold\" injuries of exocrine pancreas into considerations, particularly in the pancreas transplantation and in other major abdominal surgeries where the pancreas is exposed to cooling."} {"id": "PMID:1281974", "title": "Fragility of subcellular organelles induced by pancreatic duct obstruction in rabbits.", "content": "The effects of short-term (6 hours) pancreatic duct obstruction on the possible secretion of lysosomal enzyme into pancreatic juice and subcellular lysosomal and mitochondrial fragility were investigated in rabbits. Caerulein stimulated the secretion of amylase and cathepsin B into pancreatic juice in controls. Blockage of the pancreatic duct for 6 hours caused a significant decrease of amylase and cathepsin B output into pancreatic juice, and a significant rise in portal serum amylase and cathepsin B levels, and pancreatic amylase content and an accelerated leakage of cathepsin B from lysosomes and malate dehydrogenase from mitochondria in in-vitro preparations, as well as redistribution of cathepsin B in acinar cells. These changes tended to continue for up to 12 hours after removal of the pancreatic duct obstruction. These results indicate that under physiological conditions, lysosomal enzymes are secreted into the pancreatic juice in response to stimulation by gut hormones and that increased lysosomal fragility, mitochondrial fragility and impaired pancreatic energy charge levels are closely related to the pathogenesis of pancreatic injury in this model. Moreover, zymogen colocalized with lysosomal enzyme after duct obstruction was secreted into pancreatic juice in increased amount together with digestive enzymes; these findings suggest that lysosomal enzymes play important pathophysiological roles in pancreatic juice.", "contents": "Fragility of subcellular organelles induced by pancreatic duct obstruction in rabbits. The effects of short-term (6 hours) pancreatic duct obstruction on the possible secretion of lysosomal enzyme into pancreatic juice and subcellular lysosomal and mitochondrial fragility were investigated in rabbits. Caerulein stimulated the secretion of amylase and cathepsin B into pancreatic juice in controls. Blockage of the pancreatic duct for 6 hours caused a significant decrease of amylase and cathepsin B output into pancreatic juice, and a significant rise in portal serum amylase and cathepsin B levels, and pancreatic amylase content and an accelerated leakage of cathepsin B from lysosomes and malate dehydrogenase from mitochondria in in-vitro preparations, as well as redistribution of cathepsin B in acinar cells. These changes tended to continue for up to 12 hours after removal of the pancreatic duct obstruction. These results indicate that under physiological conditions, lysosomal enzymes are secreted into the pancreatic juice in response to stimulation by gut hormones and that increased lysosomal fragility, mitochondrial fragility and impaired pancreatic energy charge levels are closely related to the pathogenesis of pancreatic injury in this model. Moreover, zymogen colocalized with lysosomal enzyme after duct obstruction was secreted into pancreatic juice in increased amount together with digestive enzymes; these findings suggest that lysosomal enzymes play important pathophysiological roles in pancreatic juice."} {"id": "PMID:1281975", "title": "[Effects of duct reconstruction and estrogen treatment on endocrine and exocrine functions of fibrotic pancreas caused by ligation of the pancreatic duct in dogs].", "content": "After fibrotic pancreas was produced by ligation of the pancreatic ducts in mongrel dogs, effects of duct reconstruction and estrogen treatment on endocrine and exocrine function of the fibrotic pancreas were investigated. 1) K value in IV-GTT and sigma IRG in IV-ITT were significantly improved after duct reconstruction in group with estrogen treatment, especially K value was significantly improved as compared with that in group without estrogen treatment. 2) Total volume of pancreatic secretion, total amylase output and maximal bicarbonate concentration in P-S tests were improved significantly after duct reconstruction in the group with estrogen treatment, but not significantly improved in the group without estrogen treatment. 3) Histological changes of the islet and pancreatic fibrosis, caused by the pancreatic duct ligation, were also significantly improved after duct reconstruction in the group with estrogen treatment, as compared with those in the group without estrogen treatment.", "contents": "[Effects of duct reconstruction and estrogen treatment on endocrine and exocrine functions of fibrotic pancreas caused by ligation of the pancreatic duct in dogs]. After fibrotic pancreas was produced by ligation of the pancreatic ducts in mongrel dogs, effects of duct reconstruction and estrogen treatment on endocrine and exocrine function of the fibrotic pancreas were investigated. 1) K value in IV-GTT and sigma IRG in IV-ITT were significantly improved after duct reconstruction in group with estrogen treatment, especially K value was significantly improved as compared with that in group without estrogen treatment. 2) Total volume of pancreatic secretion, total amylase output and maximal bicarbonate concentration in P-S tests were improved significantly after duct reconstruction in the group with estrogen treatment, but not significantly improved in the group without estrogen treatment. 3) Histological changes of the islet and pancreatic fibrosis, caused by the pancreatic duct ligation, were also significantly improved after duct reconstruction in the group with estrogen treatment, as compared with those in the group without estrogen treatment."} {"id": "PMID:1281976", "title": "Development and characterization of Porphyromonas gingivalis-specific rat T-cell clones.", "content": "Porphyromonas gingivalis has been implicated as a major pathogen in periodontitis. To determine the role of T cells in the regulation of this disease, a method was developed for the generation and characterization of rat T-cell clones with antigen specificity to P. gingivalis whole cells. The clones studied so far demonstrated a T-helper (Th) phenotype W3/13+, W3/25+, OX8- and OX22-. These T-cell clones proliferated in vitro in response to P. gingivalis, but not to other bacteria (Prevotella intermedia, Actinobacillus actinomycetemcomitans, Wolinella recta, Fusobacterium nucleatum, Streptococcus sanguis). Limiting dilution analysis showed W3/25+, OX8- T cells preferentially respond to P. gingivalis, rather than W3/25-, OX8+ T cells. P. gingivalis-reactive W3/25+ T cells belonged to the OX22- population, suggesting that the OX22- T cells may represent memory cells. All clones tested produced interferon gamma, but not interleukin 2. The cloned T-cell F1 significantly enhanced P. gingivalis-specific antibody production (p < 0.03). The availability of these cloned T cells should bring new insight into the mechanism by which T cells regulate oral health and periodontal disease.", "contents": "Development and characterization of Porphyromonas gingivalis-specific rat T-cell clones. Porphyromonas gingivalis has been implicated as a major pathogen in periodontitis. To determine the role of T cells in the regulation of this disease, a method was developed for the generation and characterization of rat T-cell clones with antigen specificity to P. gingivalis whole cells. The clones studied so far demonstrated a T-helper (Th) phenotype W3/13+, W3/25+, OX8- and OX22-. These T-cell clones proliferated in vitro in response to P. gingivalis, but not to other bacteria (Prevotella intermedia, Actinobacillus actinomycetemcomitans, Wolinella recta, Fusobacterium nucleatum, Streptococcus sanguis). Limiting dilution analysis showed W3/25+, OX8- T cells preferentially respond to P. gingivalis, rather than W3/25-, OX8+ T cells. P. gingivalis-reactive W3/25+ T cells belonged to the OX22- population, suggesting that the OX22- T cells may represent memory cells. All clones tested produced interferon gamma, but not interleukin 2. The cloned T-cell F1 significantly enhanced P. gingivalis-specific antibody production (p < 0.03). The availability of these cloned T cells should bring new insight into the mechanism by which T cells regulate oral health and periodontal disease."} {"id": "PMID:1281977", "title": "Purification and structure of human liver aspartylglucosaminidase.", "content": "We have recently diagnosed aspartylglucosaminuria (AGU) in four members of a Canadian family. AGU is a lysosomal storage disease in which asparagine-linked glycopeptides accumulate to particularly high concentrations in liver, spleen and thyroid of affected individuals. A lesser accumulation of these glycopeptides is seen in the kidney and brain, and they are also excreted in the urine. The altered metabolism in AGU results from a deficiency of the enzyme aspartylglucosaminidase (1-aspartamido-beta-N-acetylglucosamine amidohydrolase), which hydrolyses the asparagine to N-acetylglucosamine linkages of glycoproteins and glycopeptides. We have used human liver as a source of material for the purification of aspartylglucosaminidase. The enzyme has been purified to homogeneity by using heat treatment, (NH4)2SO4 fractionation, and chromatography on concanavalin A-Sepharose, DEAE-Sepharose, sulphopropyl-Sephadex, hydroxyapatite, DEAE-cellulose and Sephadex G-100. Enzyme activity was followed by measuring colorimetrically the N-acetylglucosamine released from aspartylglucosamine at 56 degrees C. The purified enzyme protein ran at a 'native' molecular mass of 56 kDa in SDS/12.5%-PAGE gels, and the enzyme activity could be quantitatively recovered at this molecular mass by using gel slices as enzyme source in the assay. After denaturation by boiling in SDS the 56 kDa protein was lost with the corresponding appearance of polypeptides alpha,beta and beta 1, lacking enzyme activity, at 24.6, 18.4 and 17.4 kDa respectively. Treatment of heat-denatured enzyme with N-glycosidase F resulted in the following decreases in molecular mass; 24.6 to 23 kDa and 18.4 and 17.4 to 15.8 kDa. These studies indicate that human liver aspartylglucosaminidase is composed of two non-identical polypeptides, each of which is glycosylated. The N-termini of alpha,beta and beta 1 were directly accessible for sequencing, and the first 21, 26 and 22 amino acids respectively were identified.", "contents": "Purification and structure of human liver aspartylglucosaminidase. We have recently diagnosed aspartylglucosaminuria (AGU) in four members of a Canadian family. AGU is a lysosomal storage disease in which asparagine-linked glycopeptides accumulate to particularly high concentrations in liver, spleen and thyroid of affected individuals. A lesser accumulation of these glycopeptides is seen in the kidney and brain, and they are also excreted in the urine. The altered metabolism in AGU results from a deficiency of the enzyme aspartylglucosaminidase (1-aspartamido-beta-N-acetylglucosamine amidohydrolase), which hydrolyses the asparagine to N-acetylglucosamine linkages of glycoproteins and glycopeptides. We have used human liver as a source of material for the purification of aspartylglucosaminidase. The enzyme has been purified to homogeneity by using heat treatment, (NH4)2SO4 fractionation, and chromatography on concanavalin A-Sepharose, DEAE-Sepharose, sulphopropyl-Sephadex, hydroxyapatite, DEAE-cellulose and Sephadex G-100. Enzyme activity was followed by measuring colorimetrically the N-acetylglucosamine released from aspartylglucosamine at 56 degrees C. The purified enzyme protein ran at a 'native' molecular mass of 56 kDa in SDS/12.5%-PAGE gels, and the enzyme activity could be quantitatively recovered at this molecular mass by using gel slices as enzyme source in the assay. After denaturation by boiling in SDS the 56 kDa protein was lost with the corresponding appearance of polypeptides alpha,beta and beta 1, lacking enzyme activity, at 24.6, 18.4 and 17.4 kDa respectively. Treatment of heat-denatured enzyme with N-glycosidase F resulted in the following decreases in molecular mass; 24.6 to 23 kDa and 18.4 and 17.4 to 15.8 kDa. These studies indicate that human liver aspartylglucosaminidase is composed of two non-identical polypeptides, each of which is glycosylated. The N-termini of alpha,beta and beta 1 were directly accessible for sequencing, and the first 21, 26 and 22 amino acids respectively were identified."} {"id": "PMID:1281978", "title": "Application of active-phase plot to the kinetic analysis of lipoxygenase in reverse micelles.", "content": "A new plot for explaining the complex expression of the enzymic activity in reverse micelles has been developed as an extension of the theoretical model described by our group [Bru, S\u00e1nchez-Ferrer & Garc\u00eda-Carmona (1990) Biochem. J. 268, 679-684]. The plot describes the changes in the relative volume, amount of enzyme (mumoles), enzyme concentration (microM) and substrate concentration (microM) in the phase where the enzyme is active. To illustrate the usefulness of this plot, the complex activity of soya bean lipoxygenase in reverse micelles acting on its interfacial substrate, octadecadienoic acid, was studied. It showed the key parameters ruling the activity profiles of lipoxygenase with respect to micelle size (omega 0), micelle concentration (theta) and the substrate/surfactant molar ratio (rho), which have never been described before.", "contents": "Application of active-phase plot to the kinetic analysis of lipoxygenase in reverse micelles. A new plot for explaining the complex expression of the enzymic activity in reverse micelles has been developed as an extension of the theoretical model described by our group [Bru, S\u00e1nchez-Ferrer & Garc\u00eda-Carmona (1990) Biochem. J. 268, 679-684]. The plot describes the changes in the relative volume, amount of enzyme (mumoles), enzyme concentration (microM) and substrate concentration (microM) in the phase where the enzyme is active. To illustrate the usefulness of this plot, the complex activity of soya bean lipoxygenase in reverse micelles acting on its interfacial substrate, octadecadienoic acid, was studied. It showed the key parameters ruling the activity profiles of lipoxygenase with respect to micelle size (omega 0), micelle concentration (theta) and the substrate/surfactant molar ratio (rho), which have never been described before."} {"id": "PMID:1281979", "title": "Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells. Involvement of Ca2+ and Na+ in the activation of beta-glucuronidase release and superoxide production.", "content": "In human neutrophils, the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) induces increases in the intracellular free Ca2+ concentration ([Ca2+]i) with subsequent activation of beta-glucuronidase release and superoxide (O2-) production. Results from several laboratories suggest that the increase in [Ca2+]i is due to activation of non-selective cation (NSC) channels. We studied the biophysical characteristics, pharmacological modulation and functional role of NSC channels in dibutyryl cyclic AMP (Bt2cAMP)-differentiated HL-60 cells. fMLP increased [Ca2+]i by release of Ca2+ from intracellular stores and influx of Ca2+ from the extracellular space. fMLP also induced Mn2+ influx. Ca2+ and Mn2+ influxes were inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365). Under whole-cell voltage-clamp conditions, fMLP and ATP (a purinoceptor agonist) activated inward currents characterized by a linear current-voltage relationship and a reversal potential near 0 mV. NSC channels were substantially more permeable to Na+ than to Ca2+. SK&F 96365 inhibited fMLP- and ATP-stimulated currents with a half-maximal effect at about 3 microM. Pertussis toxin prevented stimulation by fMLP of NSC currents and reduced ATP-stimulated currents by about 80%. Intracellular application of the stable GDP analogue, guanosine 5'-O-[2-thio]diphosphate, completely blocked stimulation by agonists of NSC currents. In excised inside-out patches, single channel openings with an amplitude of 0.24 pA were observed in the presence of fMLP and the GTP analogue, guanosine 5'-O-[3-thio]triphosphate. The bath solution contained neither Ca2+ nor ATP. The current/voltage relationship was linear with a conductance of 4-5 pS and reversed at about 0 mV. fMLP-induced beta-glucuronidase release and O2- production were substantially reduced by replacement of extracellular CaCl2 or NaCl by ethylenebis(oxyethylenenitrilo)tetra-acetic acid and choline chloride respectively. In the absence of Ca2+ and Na+, fMLP was ineffective. SK&F 96365 inhibited fMLP-induced beta-glucuronidase release and O2- production in the presence of both Ca2+ and Na+, and in the presence of Ca2+ or Na+ alone. NaCl (25-50 mM) enhanced the basal and absolute extent of fMLP-stimulated GTP hydrolysis of heterotrimeric regulatory G-proteins in HL-60 membranes. The order of effectiveness of salts in enhancing GTP hydrolysis was LiCl > KCl > NaCl > choline chloride.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Formyl peptides and ATP stimulate Ca2+ and Na+ inward currents through non-selective cation channels via G-proteins in dibutyryl cyclic AMP-differentiated HL-60 cells. Involvement of Ca2+ and Na+ in the activation of beta-glucuronidase release and superoxide production. In human neutrophils, the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP) induces increases in the intracellular free Ca2+ concentration ([Ca2+]i) with subsequent activation of beta-glucuronidase release and superoxide (O2-) production. Results from several laboratories suggest that the increase in [Ca2+]i is due to activation of non-selective cation (NSC) channels. We studied the biophysical characteristics, pharmacological modulation and functional role of NSC channels in dibutyryl cyclic AMP (Bt2cAMP)-differentiated HL-60 cells. fMLP increased [Ca2+]i by release of Ca2+ from intracellular stores and influx of Ca2+ from the extracellular space. fMLP also induced Mn2+ influx. Ca2+ and Mn2+ influxes were inhibited by 1-(beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride (SK&F 96365). Under whole-cell voltage-clamp conditions, fMLP and ATP (a purinoceptor agonist) activated inward currents characterized by a linear current-voltage relationship and a reversal potential near 0 mV. NSC channels were substantially more permeable to Na+ than to Ca2+. SK&F 96365 inhibited fMLP- and ATP-stimulated currents with a half-maximal effect at about 3 microM. Pertussis toxin prevented stimulation by fMLP of NSC currents and reduced ATP-stimulated currents by about 80%. Intracellular application of the stable GDP analogue, guanosine 5'-O-[2-thio]diphosphate, completely blocked stimulation by agonists of NSC currents. In excised inside-out patches, single channel openings with an amplitude of 0.24 pA were observed in the presence of fMLP and the GTP analogue, guanosine 5'-O-[3-thio]triphosphate. The bath solution contained neither Ca2+ nor ATP. The current/voltage relationship was linear with a conductance of 4-5 pS and reversed at about 0 mV. fMLP-induced beta-glucuronidase release and O2- production were substantially reduced by replacement of extracellular CaCl2 or NaCl by ethylenebis(oxyethylenenitrilo)tetra-acetic acid and choline chloride respectively. In the absence of Ca2+ and Na+, fMLP was ineffective. SK&F 96365 inhibited fMLP-induced beta-glucuronidase release and O2- production in the presence of both Ca2+ and Na+, and in the presence of Ca2+ or Na+ alone. NaCl (25-50 mM) enhanced the basal and absolute extent of fMLP-stimulated GTP hydrolysis of heterotrimeric regulatory G-proteins in HL-60 membranes. The order of effectiveness of salts in enhancing GTP hydrolysis was LiCl > KCl > NaCl > choline chloride.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1281980", "title": "A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion.", "content": "Amyloid beta (A beta), the major constituent of the fibrils composing senile plaques and vascular amyloid deposits in Alzheimer's disease (AD) and related disorders, is a 39-42-residue self-aggregating degradation peptide of a larger multidomain membrane glycoprotein designated amyloid precursor protein (APP). An array of biological functions has been assigned to different APP domains, including growth regulation, neurotoxicity, inhibitory activity of serine proteinases and promotion of cell-cell and cell-matrix interactions. A beta is generated through an as-yet-unknown catabolic pathway that by-passes or inhibits the cleavage of APP within the A beta sequence. We have identified a 16 kDa intermediate APP C-terminal fragment containing A beta in leptomeningeal vessels of aged normal individuals and AD patients by means of its immunoreactivity with a panel of four different anti-(APP C-terminal) antibodies, indicating a different pathway of APP processing. Previous studies have indicated that the APP C-terminal domain is the most likely to be involved in cell-matrix interactions. A 109-amino-acid construct C109 with a sequence analogous to the C-terminal of APP (positions 587-695 of APP695), similar in length and immunoreactivity to the 16 kDa fragment, was found to promote cell adhesion. By use of synthetic peptides, this activity was initially located to the extracellular 28 residues of A beta. Inhibition studies demonstrated that the sequence RHDS (amino acids 5-8 of A beta, corresponding to residues 601-604 of APP695 was responsible for the adhesion-promoting activity. The interaction is dependent on bivalent cations and can be blocked either by the tetrapeptides RHDS and RGDS or by an anti-(beta 1 integrin) antibody. Thus, through integrin-like surface receptors, APP or its derivative proteolytic fragments containing the sequence RHDS may modulate cell-cell or cell-matrix interactions.", "contents": "A 109-amino-acid C-terminal fragment of Alzheimer's-disease amyloid precursor protein contains a sequence, -RHDS-, that promotes cell adhesion. Amyloid beta (A beta), the major constituent of the fibrils composing senile plaques and vascular amyloid deposits in Alzheimer's disease (AD) and related disorders, is a 39-42-residue self-aggregating degradation peptide of a larger multidomain membrane glycoprotein designated amyloid precursor protein (APP). An array of biological functions has been assigned to different APP domains, including growth regulation, neurotoxicity, inhibitory activity of serine proteinases and promotion of cell-cell and cell-matrix interactions. A beta is generated through an as-yet-unknown catabolic pathway that by-passes or inhibits the cleavage of APP within the A beta sequence. We have identified a 16 kDa intermediate APP C-terminal fragment containing A beta in leptomeningeal vessels of aged normal individuals and AD patients by means of its immunoreactivity with a panel of four different anti-(APP C-terminal) antibodies, indicating a different pathway of APP processing. Previous studies have indicated that the APP C-terminal domain is the most likely to be involved in cell-matrix interactions. A 109-amino-acid construct C109 with a sequence analogous to the C-terminal of APP (positions 587-695 of APP695), similar in length and immunoreactivity to the 16 kDa fragment, was found to promote cell adhesion. By use of synthetic peptides, this activity was initially located to the extracellular 28 residues of A beta. Inhibition studies demonstrated that the sequence RHDS (amino acids 5-8 of A beta, corresponding to residues 601-604 of APP695 was responsible for the adhesion-promoting activity. The interaction is dependent on bivalent cations and can be blocked either by the tetrapeptides RHDS and RGDS or by an anti-(beta 1 integrin) antibody. Thus, through integrin-like surface receptors, APP or its derivative proteolytic fragments containing the sequence RHDS may modulate cell-cell or cell-matrix interactions."} {"id": "PMID:1281981", "title": "Observations on the inhibition of HIV-1 reverse transcriptase by catechins.", "content": "The sensitivity and specificity of the inhibition of HIV-1 reverse transcriptase by various catechins have been examined. As previously reported, (-)epicatechin 3-gallate inhibits the viral polymerase. However, it is noted here that this inhibition is not observed in the presence of either serum albumin or Triton X-100. Other catechins behave similarly to (-)epicatechin 3-gallate in that they inhibit polymerase activity only in the absence of these reagents. Additionally, other DNA polymerases are inhibited to a similar degree by (-)epicatechin 3-gallate. Taken cumulatively, these results suggest that these catechins, and in particular (-)epicatechin 3-gallate, bind with no apparent selectivity and that the observed inhibition of HIV-1 reverse transcriptase is non-specific in nature.", "contents": "Observations on the inhibition of HIV-1 reverse transcriptase by catechins. The sensitivity and specificity of the inhibition of HIV-1 reverse transcriptase by various catechins have been examined. As previously reported, (-)epicatechin 3-gallate inhibits the viral polymerase. However, it is noted here that this inhibition is not observed in the presence of either serum albumin or Triton X-100. Other catechins behave similarly to (-)epicatechin 3-gallate in that they inhibit polymerase activity only in the absence of these reagents. Additionally, other DNA polymerases are inhibited to a similar degree by (-)epicatechin 3-gallate. Taken cumulatively, these results suggest that these catechins, and in particular (-)epicatechin 3-gallate, bind with no apparent selectivity and that the observed inhibition of HIV-1 reverse transcriptase is non-specific in nature."} {"id": "PMID:1281982", "title": "The effect of mevalonic acid deprivation on enzymes of DNA replication in cells emerging from quiescence.", "content": "We have investigated the biochemical basis of the mevalonate dependence of DNA replication. Stimulating quiescent rat hepatoma cells to proliferate in the presence of compactin, an inhibitor of mevalonate synthesis, prevented DNA replication in as many as 80% of these cells. The percentage of cells that failed to replicate DNA increased with the increased duration of quiescence. Aphidicolin-sensitive DNA polymerase and ornithine decarboxylase activities were selectively decreased in compactin-treated cells, whereas RNA and protein synthesis, the level of dihydrofolate reductase and aphidicolin-resistant DNA polymerase activity were unaffected. Adding putrescine, the product of ornithine decarboxylase and the precursor of other polyamines, did not restore DNA replication. Our results demonstrate that the decreased activities of at least two DNA-replication enzymes are among the proximal causes of the failure of mevalonate-deprived cells to synthesize DNA. More importantly, our data indicate that a mevalonate-dependent factor(s) is progressively depleted during quiescence, and that inability to resynthesize this factor(s) may be the ultimate cause of the failure of resting cells to replicate DNA when stimulated to proliferate in the absence of mevalonate.", "contents": "The effect of mevalonic acid deprivation on enzymes of DNA replication in cells emerging from quiescence. We have investigated the biochemical basis of the mevalonate dependence of DNA replication. Stimulating quiescent rat hepatoma cells to proliferate in the presence of compactin, an inhibitor of mevalonate synthesis, prevented DNA replication in as many as 80% of these cells. The percentage of cells that failed to replicate DNA increased with the increased duration of quiescence. Aphidicolin-sensitive DNA polymerase and ornithine decarboxylase activities were selectively decreased in compactin-treated cells, whereas RNA and protein synthesis, the level of dihydrofolate reductase and aphidicolin-resistant DNA polymerase activity were unaffected. Adding putrescine, the product of ornithine decarboxylase and the precursor of other polyamines, did not restore DNA replication. Our results demonstrate that the decreased activities of at least two DNA-replication enzymes are among the proximal causes of the failure of mevalonate-deprived cells to synthesize DNA. More importantly, our data indicate that a mevalonate-dependent factor(s) is progressively depleted during quiescence, and that inability to resynthesize this factor(s) may be the ultimate cause of the failure of resting cells to replicate DNA when stimulated to proliferate in the absence of mevalonate."} {"id": "PMID:1281983", "title": "Immunological discrimination of beta-tubulin isoforms in developing mouse brain. Post-translational modification of non-class-III beta-tubulins.", "content": "Individual beta-tubulin isoforms in developing mouse brain were characterized using immunoblotting, after preceding high-resolution isoelectric focusing, with monoclonal antibodies against different structural regions of beta-tubulin. Some of the antibodies reacted with a limited number of tubulin isoforms in all stages of brain development and in HeLa cells. The epitope for the TU-14 antibody was located in the isotype-defining domain and was present on the beta-tubulin isotypes of classes I, II and IV, but absent on the neuron-specific class-III isotype. The data suggest that non-class-III beta-tubulins in mouse brain are substrates for developmentally regulated post-translational modifications and that beta-tubulins of non-neuronal cells are also post-translationally modified.", "contents": "Immunological discrimination of beta-tubulin isoforms in developing mouse brain. Post-translational modification of non-class-III beta-tubulins. Individual beta-tubulin isoforms in developing mouse brain were characterized using immunoblotting, after preceding high-resolution isoelectric focusing, with monoclonal antibodies against different structural regions of beta-tubulin. Some of the antibodies reacted with a limited number of tubulin isoforms in all stages of brain development and in HeLa cells. The epitope for the TU-14 antibody was located in the isotype-defining domain and was present on the beta-tubulin isotypes of classes I, II and IV, but absent on the neuron-specific class-III isotype. The data suggest that non-class-III beta-tubulins in mouse brain are substrates for developmentally regulated post-translational modifications and that beta-tubulins of non-neuronal cells are also post-translationally modified."} {"id": "PMID:1281984", "title": "Heparin increases chromatin accessibility by binding the trypsin-sensitive basic residues in histones.", "content": "Recent evidence indicates that chromatin accessibility to transcription factors is of regulatory significance. The polyanion heparin is known to increase chromatin accessibility to DNAase I and to stimulate both RNA and DNA synthesis. In the present study, chromatin structure and its modification by polyanions were examined by using trypsin and micrococcal nuclease as probes. Both heparin and poly(glutamic acid) were found to be equivalent to trypsin digestion of histones in their ability to increase nuclease accessibility in chromatin. However, no increase in nuclease accessibility was observed when trypsin-digested chromatin was further treated with heparin, indicating that polyanions and trypsin are not additive in their effects on chromatin accessibility. Moreover, sucrose-gradient analysis demonstrated that heparin binds tightly to intact nucleosomes but not to trypsin-digested nucleosomes. These data suggest that polyanions interact predominantly with the trypsin-sensitive lysine and arginine residues in histone H1 and the N-terminal segments of the core histones. The possible relevance of these results to the chromatin structure of actively transcribed regions is discussed.", "contents": "Heparin increases chromatin accessibility by binding the trypsin-sensitive basic residues in histones. Recent evidence indicates that chromatin accessibility to transcription factors is of regulatory significance. The polyanion heparin is known to increase chromatin accessibility to DNAase I and to stimulate both RNA and DNA synthesis. In the present study, chromatin structure and its modification by polyanions were examined by using trypsin and micrococcal nuclease as probes. Both heparin and poly(glutamic acid) were found to be equivalent to trypsin digestion of histones in their ability to increase nuclease accessibility in chromatin. However, no increase in nuclease accessibility was observed when trypsin-digested chromatin was further treated with heparin, indicating that polyanions and trypsin are not additive in their effects on chromatin accessibility. Moreover, sucrose-gradient analysis demonstrated that heparin binds tightly to intact nucleosomes but not to trypsin-digested nucleosomes. These data suggest that polyanions interact predominantly with the trypsin-sensitive lysine and arginine residues in histone H1 and the N-terminal segments of the core histones. The possible relevance of these results to the chromatin structure of actively transcribed regions is discussed."} {"id": "PMID:1281985", "title": "Phosphatidylinositol-3-kinase is a non-tyrosine phosphorylated member of the insulin receptor signalling complex.", "content": "In rat HTC cells expressing a large number of human insulin receptors, insulin stimulated phosphatidylinositol-3-kinase (PI-3-kinase) activity. This activity was more effectively immunoprecipitated with anti-phosphotyrosine antibody (alpha-PY) than with anti-insulin receptor antibody (alpha-IR), suggesting that PI-3-kinase was not directly associated with the insulin receptor. alpha-PY immunoprecipitable PI-3 kinase activity, which was regulated by insulin, corresponded to a small pool of the total cellular PI-3-kinase activity. PI-3-kinase was not directly tyrosine phosphorylated by insulin treatment. A comparison of both catalytic activity and content of PI-3-kinase in alpha-PY immunoprecipitates indicated that after insulin treatment PI-3-kinase activity was enhanced by its association with tyrosine phosphorylated proteins. These studies suggest therefore that PI-3-kinase is a non-tyrosine phosphorylated member of the insulin receptor signalling complex.", "contents": "Phosphatidylinositol-3-kinase is a non-tyrosine phosphorylated member of the insulin receptor signalling complex. In rat HTC cells expressing a large number of human insulin receptors, insulin stimulated phosphatidylinositol-3-kinase (PI-3-kinase) activity. This activity was more effectively immunoprecipitated with anti-phosphotyrosine antibody (alpha-PY) than with anti-insulin receptor antibody (alpha-IR), suggesting that PI-3-kinase was not directly associated with the insulin receptor. alpha-PY immunoprecipitable PI-3 kinase activity, which was regulated by insulin, corresponded to a small pool of the total cellular PI-3-kinase activity. PI-3-kinase was not directly tyrosine phosphorylated by insulin treatment. A comparison of both catalytic activity and content of PI-3-kinase in alpha-PY immunoprecipitates indicated that after insulin treatment PI-3-kinase activity was enhanced by its association with tyrosine phosphorylated proteins. These studies suggest therefore that PI-3-kinase is a non-tyrosine phosphorylated member of the insulin receptor signalling complex."} {"id": "PMID:1281986", "title": "Post-transcriptional regulation of insulin-like growth factor binding protein-2 mRNA in diabetic rat liver.", "content": "IGFBP-1 and IGFBP-2 mRNAs are increased in the livers of streptozotocin-diabetic rats. A corresponding increase is observed in transcription of the IGFBP-1 but not the IGFBP-2 gene, indicating that the increase in steady-state levels of IGFBP-2 mRNA is a post-transcriptional effect. IGFBP-1 and IGFBP-2 mRNAs also differ in the rapidity of their response to insulin treatment: hepatic IGFBP-1 mRNA is normalized within 1 h, IGFBP-2 mRNA decreases more slowly. These differences suggest that IGFBP-2 may provide more chronic adaptation to metabolic change than IGFBP-1.", "contents": "Post-transcriptional regulation of insulin-like growth factor binding protein-2 mRNA in diabetic rat liver. IGFBP-1 and IGFBP-2 mRNAs are increased in the livers of streptozotocin-diabetic rats. A corresponding increase is observed in transcription of the IGFBP-1 but not the IGFBP-2 gene, indicating that the increase in steady-state levels of IGFBP-2 mRNA is a post-transcriptional effect. IGFBP-1 and IGFBP-2 mRNAs also differ in the rapidity of their response to insulin treatment: hepatic IGFBP-1 mRNA is normalized within 1 h, IGFBP-2 mRNA decreases more slowly. These differences suggest that IGFBP-2 may provide more chronic adaptation to metabolic change than IGFBP-1."} {"id": "PMID:1281987", "title": "Bilayers containing calcium ionophore A23187 form channels.", "content": "For the first time, based on bilayer membrane conductance experiments, it has been shown that A23187, a carboxylic calcium ionophore, incorporated in lipid bilayers gives single channel currents similar to the well known gramicidin channel. The current characteristics indicate the possibility that the transmembrane ion transport by this important calcium ionophore is initially by a carrier mechanism but with time is by a channel or pore mechanism due to the aggregation of the molecule in a lipid matrix.", "contents": "Bilayers containing calcium ionophore A23187 form channels. For the first time, based on bilayer membrane conductance experiments, it has been shown that A23187, a carboxylic calcium ionophore, incorporated in lipid bilayers gives single channel currents similar to the well known gramicidin channel. The current characteristics indicate the possibility that the transmembrane ion transport by this important calcium ionophore is initially by a carrier mechanism but with time is by a channel or pore mechanism due to the aggregation of the molecule in a lipid matrix."} {"id": "PMID:1281988", "title": "A mutation generating a stop codon in the alpha-L-fucosidase gene of a fucosidosis patient.", "content": "Fucosidosis is an autosomal recessive, lysosomal storage disease featured by deficient activity of alpha-L-fucosidase. Lymphoid cell lines from a fucosidosis patient (JT) and a healthy individual (control) contained alpha-L-fucosidase mRNA of the same size, 2.3 Kb, as determined by Northern blot analysis. cDNA was prepared from alpha-L-fucosidase mRNA of JT and control cells and each cDNA was amplified by the polymerase chain reaction. Direct DNA sequencing of the amplified products revealed a single mutation in JT, a G1141-->T transition. This changed the codon (GAA) for Glu-375 to a stop codon (UAA). Amplification and sequencing of the area containing the G1141-->T transition in genomic DNA of JT and control cells demonstrated that the mutation was homozygous in JT. Analysis of cDNA and genomic DNA derived from lymphoid cells of mother JT revealed her to be heterozygous (G and T) at position 1141. The G1141-->T mutation is probably responsible for disease in JT.", "contents": "A mutation generating a stop codon in the alpha-L-fucosidase gene of a fucosidosis patient. Fucosidosis is an autosomal recessive, lysosomal storage disease featured by deficient activity of alpha-L-fucosidase. Lymphoid cell lines from a fucosidosis patient (JT) and a healthy individual (control) contained alpha-L-fucosidase mRNA of the same size, 2.3 Kb, as determined by Northern blot analysis. cDNA was prepared from alpha-L-fucosidase mRNA of JT and control cells and each cDNA was amplified by the polymerase chain reaction. Direct DNA sequencing of the amplified products revealed a single mutation in JT, a G1141-->T transition. This changed the codon (GAA) for Glu-375 to a stop codon (UAA). Amplification and sequencing of the area containing the G1141-->T transition in genomic DNA of JT and control cells demonstrated that the mutation was homozygous in JT. Analysis of cDNA and genomic DNA derived from lymphoid cells of mother JT revealed her to be heterozygous (G and T) at position 1141. The G1141-->T mutation is probably responsible for disease in JT."} {"id": "PMID:1281989", "title": "Identification of a novel tyrosine kinase receptor-like molecule in neuroblastomas.", "content": "Growth factor receptors are important determinants of both normal and abnormal cell growth. We have now used degenerate primers designed from conserved tyrosine kinase domains to identify and clone a novel receptor-like molecule (designated Nbtk-1) from a NB41 mouse neuroblastoma cell line. Nbtk-1 is related to the met proto-oncogene family of tyrosine kinase receptors. Transcripts of approximately 2.1 and 2.6 kb have been found in mouse cell lines and one transcript of approximately 3 kb in human cell lines and in a wide range of primary human tumors, such as neuroblastomas, primitive neuroectodermal tumors (PNETs), Wilms' tumors, and melanomas and in the corresponding normal human tissues. These observations suggest that Nbtk-1 may have important roles in normal and tumor cell growth.", "contents": "Identification of a novel tyrosine kinase receptor-like molecule in neuroblastomas. Growth factor receptors are important determinants of both normal and abnormal cell growth. We have now used degenerate primers designed from conserved tyrosine kinase domains to identify and clone a novel receptor-like molecule (designated Nbtk-1) from a NB41 mouse neuroblastoma cell line. Nbtk-1 is related to the met proto-oncogene family of tyrosine kinase receptors. Transcripts of approximately 2.1 and 2.6 kb have been found in mouse cell lines and one transcript of approximately 3 kb in human cell lines and in a wide range of primary human tumors, such as neuroblastomas, primitive neuroectodermal tumors (PNETs), Wilms' tumors, and melanomas and in the corresponding normal human tissues. These observations suggest that Nbtk-1 may have important roles in normal and tumor cell growth."} {"id": "PMID:1281990", "title": "Duck hepatitis B virus polymerase produced by in vitro transcription and translation possesses DNA polymerase and reverse transcriptase activities.", "content": "Activities of the hepadnavirus polymerases are known to include those of DNA polymerase, reverse transcriptase and RNase H. To date, it has been difficult or impossible to clone and express the product as an active enzyme. In this study, full length capped RNA encoding Duck Hepatitis B Virus (DHBV) polymerase was produced by in vitro transcription from a T7 promoter. The RNA was translated in a rabbit reticulocyte lysate system and produced an 35S-Methionine labelled 79 Kd band on SDS-polyacrylamide gel electrophoresis. The translation product showed DNA polymerase and reverse transcriptase activities on exogenous templates (respectively) of DNA or RNA with random DNA hexamer primers. The same RNA transcripts were also microinjected into Xenopus oocytes, but appeared to be toxic and gave no detectable translation product. Production of hepadnavirus polymerase by in vitro transcription/translation may provide a useful tool for structure/function and pharmacological studies on this important group of polymerases.", "contents": "Duck hepatitis B virus polymerase produced by in vitro transcription and translation possesses DNA polymerase and reverse transcriptase activities. Activities of the hepadnavirus polymerases are known to include those of DNA polymerase, reverse transcriptase and RNase H. To date, it has been difficult or impossible to clone and express the product as an active enzyme. In this study, full length capped RNA encoding Duck Hepatitis B Virus (DHBV) polymerase was produced by in vitro transcription from a T7 promoter. The RNA was translated in a rabbit reticulocyte lysate system and produced an 35S-Methionine labelled 79 Kd band on SDS-polyacrylamide gel electrophoresis. The translation product showed DNA polymerase and reverse transcriptase activities on exogenous templates (respectively) of DNA or RNA with random DNA hexamer primers. The same RNA transcripts were also microinjected into Xenopus oocytes, but appeared to be toxic and gave no detectable translation product. Production of hepadnavirus polymerase by in vitro transcription/translation may provide a useful tool for structure/function and pharmacological studies on this important group of polymerases."} {"id": "PMID:1281991", "title": "Epidermal growth factor enhances insulin-like growth factor binding protein-1 synthesis in human hepatoma cells.", "content": "Epidermal growth factor (EGF) was found to induce a rapid 2-fold increase in the amount of insulin-like growth factor binding protein-1 (IGFBP-1) mRNA in human hepatoma Hep2G cells, and this was accompanied by a 2-fold increase in IGFBP-1 secretion. A protein synthesis inhibitor cycloheximide (CHX) caused a 2-3-fold increase in the amount of IGFBP-1 mRNA, which could be accounted for the observed stabilization in decay of IGFBP-1 mRNA after CHX treatment. In nuclear run-on transcription experiments neither EGF nor CHX affected the transcription rate of the IGFBP-1 gene. It is concluded that EGF increases IGFBP-1 secretion rapidly by enhancing IGFBP-1 mRNA accumulation, and the addition of a protein synthesis inhibitor results in a specific increment of IGFBP-1 mRNA, suggesting that a labile protein repressor protein is involved in the turnover IGFBP-1 mRNA.", "contents": "Epidermal growth factor enhances insulin-like growth factor binding protein-1 synthesis in human hepatoma cells. Epidermal growth factor (EGF) was found to induce a rapid 2-fold increase in the amount of insulin-like growth factor binding protein-1 (IGFBP-1) mRNA in human hepatoma Hep2G cells, and this was accompanied by a 2-fold increase in IGFBP-1 secretion. A protein synthesis inhibitor cycloheximide (CHX) caused a 2-3-fold increase in the amount of IGFBP-1 mRNA, which could be accounted for the observed stabilization in decay of IGFBP-1 mRNA after CHX treatment. In nuclear run-on transcription experiments neither EGF nor CHX affected the transcription rate of the IGFBP-1 gene. It is concluded that EGF increases IGFBP-1 secretion rapidly by enhancing IGFBP-1 mRNA accumulation, and the addition of a protein synthesis inhibitor results in a specific increment of IGFBP-1 mRNA, suggesting that a labile protein repressor protein is involved in the turnover IGFBP-1 mRNA."} {"id": "PMID:1281992", "title": "ET-1 released histamine from guinea pig pulmonary but not peritoneal mast cells.", "content": "Endothelin(ET)-1 triggered histamine release of mast cells from pulmonary tissue but not from the peritoneal cavity of guinea pigs. The observed difference in response to ET-1 was attributable to a quantitative difference in ET-1 binding sites between both cells. The concentrations of ET-1 required for half maximal release of histamine and half maximal binding of [125I]ET-1 were approximately 0.05 and 0.08 nM, respectively. The release of histamine by ET-1 was a Ca(2+)-dependent but not a cytotoxic process. These observations, taken together, suggest that ET-1 induces histamine release from mast cells in a receptor-dependent fashion.", "contents": "ET-1 released histamine from guinea pig pulmonary but not peritoneal mast cells. Endothelin(ET)-1 triggered histamine release of mast cells from pulmonary tissue but not from the peritoneal cavity of guinea pigs. The observed difference in response to ET-1 was attributable to a quantitative difference in ET-1 binding sites between both cells. The concentrations of ET-1 required for half maximal release of histamine and half maximal binding of [125I]ET-1 were approximately 0.05 and 0.08 nM, respectively. The release of histamine by ET-1 was a Ca(2+)-dependent but not a cytotoxic process. These observations, taken together, suggest that ET-1 induces histamine release from mast cells in a receptor-dependent fashion."} {"id": "PMID:1281993", "title": "Isolation of a cDNA clone for beta 1-4 galactosyltransferase from embryonic chicken brain and comparison to its mammalian homologs.", "content": "Based on the observed biochemical and immunological similarities between bovine beta 1-4 galactosyltransferase (GalT) and a developmentally regulated galactosyltransferase (GalT-4; UDP-Gal:Lc3 beta 1-4 GalT) from embryonic chicken brain, a genetic similarity between the two enzymes has been postulated. To test our hypothesis, we have employed a reverse transcription-polymerase chain reaction (RT-PCR)based approach and isolated a approximately 600 bp cDNA clone from embryonic chicken brain mRNA. Our results indicate that, within the approximately 600 bp fragment, the avian cDNA nucleotide sequence is 74% homologous to the human beta 1-4 galactosyltransferase cDNA. Similarity and identity between the predicted amino acid sequences of the two galactosyltransferases are 75% and 61%, respectively. Similar to its mammalian counterparts, the embryonic chicken brain galactosyltransferase gene appears to encode multiple mRNA transcripts (2.3 and 1.4 kb) and shows multiple bands on a Southern blot (18.6, 12.9, 10.5 and 3.7 kb) indicating that the avian gene is either polyexonic and/or it belongs to a multiple gene family.", "contents": "Isolation of a cDNA clone for beta 1-4 galactosyltransferase from embryonic chicken brain and comparison to its mammalian homologs. Based on the observed biochemical and immunological similarities between bovine beta 1-4 galactosyltransferase (GalT) and a developmentally regulated galactosyltransferase (GalT-4; UDP-Gal:Lc3 beta 1-4 GalT) from embryonic chicken brain, a genetic similarity between the two enzymes has been postulated. To test our hypothesis, we have employed a reverse transcription-polymerase chain reaction (RT-PCR)based approach and isolated a approximately 600 bp cDNA clone from embryonic chicken brain mRNA. Our results indicate that, within the approximately 600 bp fragment, the avian cDNA nucleotide sequence is 74% homologous to the human beta 1-4 galactosyltransferase cDNA. Similarity and identity between the predicted amino acid sequences of the two galactosyltransferases are 75% and 61%, respectively. Similar to its mammalian counterparts, the embryonic chicken brain galactosyltransferase gene appears to encode multiple mRNA transcripts (2.3 and 1.4 kb) and shows multiple bands on a Southern blot (18.6, 12.9, 10.5 and 3.7 kb) indicating that the avian gene is either polyexonic and/or it belongs to a multiple gene family."} {"id": "PMID:1281994", "title": "Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha.", "content": "Transforming growth factor-alpha(TGF-alpha), homologous to epidermal growth factor(EGF), is closely involved in hyperproliferation of human keratinocytes. Psoriasis is a common hyperproliferative skin disease characterized by hyperproliferation of keratinocytes and abnormal development of dermal capillary networks. In this study, we have examined whether keratinocytes could enhance angiogenesis. TGF-alpha or EGF efficiently stimulated formation of tubular-like structures of human omental microvascular endothelial(HOME) cells in type I collagen gels. Human keratinocytes produced TGF-alpha. To examine whether co-cultured keratinocytes could induce tubulogenesis of HOME cells in collagen gel, we have developed a co-culture system with human keratinocytes. Surprisingly, there appeared new development of many tubular-like structures of HOME cells in collagen gels when co-cultured with keratinocytes. This keratinocytes-dependent tubulogenesis was almost completely blocked when anti-TGF-alpha-antibody was present. The TGF-alpha molecules derived from keratinocytes appeared to enhance tubulogenesis of human microvascular endothelial cells. We propose the hypothesis that secretory TGF-alpha from human keratinocytes may promote an autocrine loop to proliferate the skin keratinocytes and also a paracrine loop to induce the skin angiogenesis.", "contents": "Induction of human microvascular endothelial tubular morphogenesis by human keratinocytes: involvement of transforming growth factor-alpha. Transforming growth factor-alpha(TGF-alpha), homologous to epidermal growth factor(EGF), is closely involved in hyperproliferation of human keratinocytes. Psoriasis is a common hyperproliferative skin disease characterized by hyperproliferation of keratinocytes and abnormal development of dermal capillary networks. In this study, we have examined whether keratinocytes could enhance angiogenesis. TGF-alpha or EGF efficiently stimulated formation of tubular-like structures of human omental microvascular endothelial(HOME) cells in type I collagen gels. Human keratinocytes produced TGF-alpha. To examine whether co-cultured keratinocytes could induce tubulogenesis of HOME cells in collagen gel, we have developed a co-culture system with human keratinocytes. Surprisingly, there appeared new development of many tubular-like structures of HOME cells in collagen gels when co-cultured with keratinocytes. This keratinocytes-dependent tubulogenesis was almost completely blocked when anti-TGF-alpha-antibody was present. The TGF-alpha molecules derived from keratinocytes appeared to enhance tubulogenesis of human microvascular endothelial cells. We propose the hypothesis that secretory TGF-alpha from human keratinocytes may promote an autocrine loop to proliferate the skin keratinocytes and also a paracrine loop to induce the skin angiogenesis."} {"id": "PMID:1281995", "title": "Molecular cloning and characterization of the platelet-activating factor receptor gene expressed in the human heart.", "content": "PAF decreases cardiac contractility and blood pressure. To characterize the cardiac PAF receptor, we screened a human ventricular cDNA library in a low stringency condition, using a PCR product derived from guinea pig lung PAF receptor as a probe. Four clones were obtained and named HV1-4. In Xenopus oocytes injected with cRNA derived from HV3 or 4 but not from HV1 or 2, PAF elicited a Ca(2+)-activated Cl- current. HV3 and HV4 were duplicate clones, encoding a 342 amino-acid polypeptide which was identical to that of the human leukocyte PAF receptor. However, a portion of the 5' untranslated region of HV3 (or 4) was different from that of the leukocyte receptor cDNA. Northern blotting of human ventricles and atria using the HV3 insert showed a single band of approximately 4 kb. These results suggest a tissue-specific translational mechanism responsible for regulation of the expression of the PAF receptor mRNA in these tissues.", "contents": "Molecular cloning and characterization of the platelet-activating factor receptor gene expressed in the human heart. PAF decreases cardiac contractility and blood pressure. To characterize the cardiac PAF receptor, we screened a human ventricular cDNA library in a low stringency condition, using a PCR product derived from guinea pig lung PAF receptor as a probe. Four clones were obtained and named HV1-4. In Xenopus oocytes injected with cRNA derived from HV3 or 4 but not from HV1 or 2, PAF elicited a Ca(2+)-activated Cl- current. HV3 and HV4 were duplicate clones, encoding a 342 amino-acid polypeptide which was identical to that of the human leukocyte PAF receptor. However, a portion of the 5' untranslated region of HV3 (or 4) was different from that of the leukocyte receptor cDNA. Northern blotting of human ventricles and atria using the HV3 insert showed a single band of approximately 4 kb. These results suggest a tissue-specific translational mechanism responsible for regulation of the expression of the PAF receptor mRNA in these tissues."} {"id": "PMID:1281996", "title": "Purification and characterization of a novel growth factor (FF-GF) synthesized by a rat hepatoma cell line, FF101.", "content": "A rat hepatoma cell line, FF101, established in serum-free, protein-free medium, synthesizes a growth factor(FF-GF). FF-GF was purified by gel filtration chromatography, cation-exchange chromatography and isoelectric focusing. Purified FF-GF was revealed as a single band on SDS-gel electrophoresis and its molecular weight was estimated to be 70 KDa. FF-GF stimulated DNA synthesis of various cells from different origins. The growth-promoting activities of FF-GF were abolished by treating with protease, dithiothreitol, acid and heating, whereas its activity was not inhibited by antibodies against acidic and basic fibroblast growth factors. These results indicate that FF-GF is a novel growth factor.", "contents": "Purification and characterization of a novel growth factor (FF-GF) synthesized by a rat hepatoma cell line, FF101. A rat hepatoma cell line, FF101, established in serum-free, protein-free medium, synthesizes a growth factor(FF-GF). FF-GF was purified by gel filtration chromatography, cation-exchange chromatography and isoelectric focusing. Purified FF-GF was revealed as a single band on SDS-gel electrophoresis and its molecular weight was estimated to be 70 KDa. FF-GF stimulated DNA synthesis of various cells from different origins. The growth-promoting activities of FF-GF were abolished by treating with protease, dithiothreitol, acid and heating, whereas its activity was not inhibited by antibodies against acidic and basic fibroblast growth factors. These results indicate that FF-GF is a novel growth factor."} {"id": "PMID:1281997", "title": "Growth stimulation of rat fetal hepatocytes in response to hepatocyte growth factor: modulation of c-myc and c-fos expression.", "content": "Hepatocyte growth factor, which is a potent growth factor for primary cultured adult hepatocytes, strongly stimulated DNA synthesis of rat fetal (20-day of gestation) hepatocytes. Its mitogenic capacity, measured as (3H)-thymidine incorporation into acid precipitable material was dose dependent, being detectable at 1 ng/ml and maximal at 5 ng/ml. Over 15% of the cells entered into S-phase and mitosis as judged by flow cytometric analysis of the cell cycle. HGF had additive effects with transforming growth factor-alpha, whereas transforming growth factor-beta strongly inhibited DNA synthesis of fetal hepatocytes stimulated by HGF. HGF induced c-fos and c-myc expression in a time-dependent manner, with a maximum at 30 min for c-fos and 8 h for c-myc. These results suggest that HGF may act as a proliferative factor during fetal liver growth.", "contents": "Growth stimulation of rat fetal hepatocytes in response to hepatocyte growth factor: modulation of c-myc and c-fos expression. Hepatocyte growth factor, which is a potent growth factor for primary cultured adult hepatocytes, strongly stimulated DNA synthesis of rat fetal (20-day of gestation) hepatocytes. Its mitogenic capacity, measured as (3H)-thymidine incorporation into acid precipitable material was dose dependent, being detectable at 1 ng/ml and maximal at 5 ng/ml. Over 15% of the cells entered into S-phase and mitosis as judged by flow cytometric analysis of the cell cycle. HGF had additive effects with transforming growth factor-alpha, whereas transforming growth factor-beta strongly inhibited DNA synthesis of fetal hepatocytes stimulated by HGF. HGF induced c-fos and c-myc expression in a time-dependent manner, with a maximum at 30 min for c-fos and 8 h for c-myc. These results suggest that HGF may act as a proliferative factor during fetal liver growth."} {"id": "PMID:1281998", "title": "Chromosomal band assignments of the genes encoding human FKBP12 and FKBP13.", "content": "Human FKBP12 and FKBP13 are encoded by distinct genes designated FKBP1 and FKBP2, respectively. Human FKBP1 was previously characterized. The characterization of human FKBP2 is described. FKBP2 is three kb in length and contains six exons. Fluorescence in situ hybridization of FKBP1 and FKBP2 genomic probes to metaphase chromosomes localized FKBP1 to human chromosome 20 band p13 and FKBP2 to human chromosome 11 band q13.1-q13.3.", "contents": "Chromosomal band assignments of the genes encoding human FKBP12 and FKBP13. Human FKBP12 and FKBP13 are encoded by distinct genes designated FKBP1 and FKBP2, respectively. Human FKBP1 was previously characterized. The characterization of human FKBP2 is described. FKBP2 is three kb in length and contains six exons. Fluorescence in situ hybridization of FKBP1 and FKBP2 genomic probes to metaphase chromosomes localized FKBP1 to human chromosome 20 band p13 and FKBP2 to human chromosome 11 band q13.1-q13.3."} {"id": "PMID:1281999", "title": "Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro.", "content": "Vascular endothelial growth factor (VEGF), also known as vascular permeability factor or vasculotropin, is a recently characterized endothelial-specific mitogen which is angiogenic in vivo. Here we demonstrate that VEGF is angiogenic in vitro: when added to microvascular endothelial cells grown on the surface of three-dimensional collagen gels, VEGF induces the cells to invade the underlying matrix and to form capillary-like tubules, with an optimal effect at approximately 2.2nM (100ng/ml). When compared to basic fibroblast growth factor (bFGF) at equimolar (0.5nM) concentrations, VEGF was about half as potent. The most striking effect was seen in combination with bFGF: when added simultaneously, VEGF and bFGF induced an in vitro angiogenic response which was far greater than additive, and which occurred with greater rapidity than the response to either cytokine alone. These results demonstrate that like bFGF, VEGF induces an angiogenic response via a direct effect on endothelial cells, and that by acting in concert, these two cytokines have a potent synergistic effect on the induction of angiogenesis in vitro. We suggest that the synergism between VEGF and bFGF plays an important role in the control of angiogenesis in vivo.", "contents": "Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Vascular endothelial growth factor (VEGF), also known as vascular permeability factor or vasculotropin, is a recently characterized endothelial-specific mitogen which is angiogenic in vivo. Here we demonstrate that VEGF is angiogenic in vitro: when added to microvascular endothelial cells grown on the surface of three-dimensional collagen gels, VEGF induces the cells to invade the underlying matrix and to form capillary-like tubules, with an optimal effect at approximately 2.2nM (100ng/ml). When compared to basic fibroblast growth factor (bFGF) at equimolar (0.5nM) concentrations, VEGF was about half as potent. The most striking effect was seen in combination with bFGF: when added simultaneously, VEGF and bFGF induced an in vitro angiogenic response which was far greater than additive, and which occurred with greater rapidity than the response to either cytokine alone. These results demonstrate that like bFGF, VEGF induces an angiogenic response via a direct effect on endothelial cells, and that by acting in concert, these two cytokines have a potent synergistic effect on the induction of angiogenesis in vitro. We suggest that the synergism between VEGF and bFGF plays an important role in the control of angiogenesis in vivo."} {"id": "PMID:1282000", "title": "Down regulation of CD4 expression in cultured microglia by immunosuppressants and lipopolysaccharide.", "content": "Microglia, brain macrophages, are thought to be the primary target of HIV-1 infection in the brain, because they exclusively express the CD4 antigen which is effectively used for viral entry. The expression of CD4 mRNA in cultured microglia could be detected by the reverse-PCR method. Using this and immunohistochemical staining, we found that the immunosuppressants cyclosporin A and FK506 decreased CD4 expression in cultured murine microglia without causing any significant decrease in cell viability. FK506 was more potent than cyclosporin A. Lipopolysaccharide also decreased CD4 mRNA expression in microglia. The effects of immunosuppressants and lipopolysaccharide seemed to be specific for microglia since these chemicals did not alter the CD4 expression in lymphocytes or peritoneal macrophages. These agents, if modified to pass through the blood-brain barrier, may prevent viral spread of HIV-1 infection in the central nervous system and the AIDS-dementia complex.", "contents": "Down regulation of CD4 expression in cultured microglia by immunosuppressants and lipopolysaccharide. Microglia, brain macrophages, are thought to be the primary target of HIV-1 infection in the brain, because they exclusively express the CD4 antigen which is effectively used for viral entry. The expression of CD4 mRNA in cultured microglia could be detected by the reverse-PCR method. Using this and immunohistochemical staining, we found that the immunosuppressants cyclosporin A and FK506 decreased CD4 expression in cultured murine microglia without causing any significant decrease in cell viability. FK506 was more potent than cyclosporin A. Lipopolysaccharide also decreased CD4 mRNA expression in microglia. The effects of immunosuppressants and lipopolysaccharide seemed to be specific for microglia since these chemicals did not alter the CD4 expression in lymphocytes or peritoneal macrophages. These agents, if modified to pass through the blood-brain barrier, may prevent viral spread of HIV-1 infection in the central nervous system and the AIDS-dementia complex."} {"id": "PMID:1282001", "title": "Comparison of gene expression of extracellular matrix molecules in brain microvascular endothelial cells and astrocytes.", "content": "By use of random-primed cDNA probes the expression of extracellular matrix molecules in cerebral microvascular endothelial cells (cEC) and in astrocytes from mouse brain was examined. Two phenotypically different batches of cloned cEC were used. Expression of major adhesive ECM molecules, constituting the endothelial basement membrane (i.e., fibronectin, laminin A, B and collagen IV) and of other attachment factors, such as SPARC (osteonectin), tenascin and thrombospondin 1, was examined. We have demonstrated that cEC of different morphology display variations in the expression of fibronectin (FN), thrombospondin 1 (TSP1) and collagen IV (C IV). Astrocytes were shown to contain FN, TSP1, TN and SPARC mRNA. Unexpectedly, SPARC mRNA could not be detected in any of the capillary endothelial cells examined. Therefore, we suggest that astrocytes are likely to be involved in endothelial differentiation and function in the central nervous system via ECM molecule secretion.", "contents": "Comparison of gene expression of extracellular matrix molecules in brain microvascular endothelial cells and astrocytes. By use of random-primed cDNA probes the expression of extracellular matrix molecules in cerebral microvascular endothelial cells (cEC) and in astrocytes from mouse brain was examined. Two phenotypically different batches of cloned cEC were used. Expression of major adhesive ECM molecules, constituting the endothelial basement membrane (i.e., fibronectin, laminin A, B and collagen IV) and of other attachment factors, such as SPARC (osteonectin), tenascin and thrombospondin 1, was examined. We have demonstrated that cEC of different morphology display variations in the expression of fibronectin (FN), thrombospondin 1 (TSP1) and collagen IV (C IV). Astrocytes were shown to contain FN, TSP1, TN and SPARC mRNA. Unexpectedly, SPARC mRNA could not be detected in any of the capillary endothelial cells examined. Therefore, we suggest that astrocytes are likely to be involved in endothelial differentiation and function in the central nervous system via ECM molecule secretion."} {"id": "PMID:1282002", "title": "Molecular cloning of the carboxy terminus of a canine tracheobronchial mucin.", "content": "A cDNA library constructed from canine tracheal mRNA was screened with polyclonal antiserum specific to canine tracheal apomucin (CTM-A). Eight antibody reactive clones were isolated and purified to clonality. One of the clones, designated pCTM-A, had a 1.7 kb insert and included a single open reading frame with a poly (A)+ tail. The amino acid composition of the encoded protein was consistent with that expected for CTM-A. The fusion protein produced by cloning the 1.7 kb insert in the pMALc expression vector reacted with the purified anti-apomucin CTM-A antibody. Also, polyclonal antibodies raised to the purified protein product encoded by pCTM-A reacted with deglycosylated CTM-A confirming that this clone does indeed code for apomucin CTM-A. This is the first report of a cDNA encoding the C-terminus of a canine tracheal mucin.", "contents": "Molecular cloning of the carboxy terminus of a canine tracheobronchial mucin. A cDNA library constructed from canine tracheal mRNA was screened with polyclonal antiserum specific to canine tracheal apomucin (CTM-A). Eight antibody reactive clones were isolated and purified to clonality. One of the clones, designated pCTM-A, had a 1.7 kb insert and included a single open reading frame with a poly (A)+ tail. The amino acid composition of the encoded protein was consistent with that expected for CTM-A. The fusion protein produced by cloning the 1.7 kb insert in the pMALc expression vector reacted with the purified anti-apomucin CTM-A antibody. Also, polyclonal antibodies raised to the purified protein product encoded by pCTM-A reacted with deglycosylated CTM-A confirming that this clone does indeed code for apomucin CTM-A. This is the first report of a cDNA encoding the C-terminus of a canine tracheal mucin."} {"id": "PMID:1282003", "title": "Inhibition of repair of bleomycin-induced DNA strand breaks by 2'-deoxycoformycin and its effect on antitumor activity in L5178Y lymphoblasts.", "content": "We have observed previously that treatment of plateau-phase L5178Y murine lymphoblasts in vitro with 2'-deoxycoformycin plus deoxyadenosine (dCF/dAdo) can inhibit the repair of X-irradiation-induced DNA single-strand breaks (SSB) in these cells and that this effect is associated with synergistic cell kill. In this study we examined the effect of a combination treatment of plateau-phase L5178Y cells with bleomycin (BLM) plus dCF/dAdo. Incubation of BLM-treated cells with dCF/dAdo resulted in significant inhibition of the repair of BLM-induced DNA SSB. However, an additive, but not a synergistic, increase in cell kill was observed when cells were treated with a combination of BLM plus dCF/dAdo.", "contents": "Inhibition of repair of bleomycin-induced DNA strand breaks by 2'-deoxycoformycin and its effect on antitumor activity in L5178Y lymphoblasts. We have observed previously that treatment of plateau-phase L5178Y murine lymphoblasts in vitro with 2'-deoxycoformycin plus deoxyadenosine (dCF/dAdo) can inhibit the repair of X-irradiation-induced DNA single-strand breaks (SSB) in these cells and that this effect is associated with synergistic cell kill. In this study we examined the effect of a combination treatment of plateau-phase L5178Y cells with bleomycin (BLM) plus dCF/dAdo. Incubation of BLM-treated cells with dCF/dAdo resulted in significant inhibition of the repair of BLM-induced DNA SSB. However, an additive, but not a synergistic, increase in cell kill was observed when cells were treated with a combination of BLM plus dCF/dAdo."} {"id": "PMID:1282004", "title": "Alteration of mice L-tryptophan metabolism by the organophosphorous acid triester diazinon.", "content": "Diazinon [O,O-diethyl O-(2-isopropyl-6-methyl-4- pyrimidinyl)phosphorothioate] altered the formation of several L-tryptophan metabolites associated with the L-kynurenine pathway in mice. Liver kynurenine formamidase was inhibited almost completely by diazinon (10 mg/kg). The enzyme inhibition resulted in reduced L-kynurenine biosynthesis in livers with a concomitant accumulation of N-formyl-L-kynurenine. In contrast to the liver, plasma L-kynurenine increased up to 5-fold in diazinon-treated mice. Consequently, the urinary excretion of xanthurenic acid and kynurenic acid was raised 5- to 15-fold. The revelation of this novel mechanism of diazinon action is an important piece of information needed for a better understanding of the noncholinergic toxicity of organophosphorous acid triesters and methylcarbamates.", "contents": "Alteration of mice L-tryptophan metabolism by the organophosphorous acid triester diazinon. Diazinon [O,O-diethyl O-(2-isopropyl-6-methyl-4- pyrimidinyl)phosphorothioate] altered the formation of several L-tryptophan metabolites associated with the L-kynurenine pathway in mice. Liver kynurenine formamidase was inhibited almost completely by diazinon (10 mg/kg). The enzyme inhibition resulted in reduced L-kynurenine biosynthesis in livers with a concomitant accumulation of N-formyl-L-kynurenine. In contrast to the liver, plasma L-kynurenine increased up to 5-fold in diazinon-treated mice. Consequently, the urinary excretion of xanthurenic acid and kynurenic acid was raised 5- to 15-fold. The revelation of this novel mechanism of diazinon action is an important piece of information needed for a better understanding of the noncholinergic toxicity of organophosphorous acid triesters and methylcarbamates."} {"id": "PMID:1282005", "title": "Inhibition of RNA polymerase by captan at both DNA and substrate binding sites.", "content": "RNA synthesis carried out in vitro by Escherichia coli RNA polymerase was inhibited irreversibly by captan when T7 DNA was used as template. An earlier report and this one show that captan blocks the DNA binding site on the enzyme. Herein, it is also revealed that captan acts at the nucleoside triphosphate (NTP) binding site, and kinetic relationships of the action of captan at the two sites are detailed. The inhibition by captan via the DNA binding site of the enzyme was confirmed by kinetic studies and it was further shown that [14C]captan bound to the beta' subunit of RNA polymerase. This subunit contains the DNA binding site. Competitive-like inhibition by captan versus UTP led to the conclusion that captan also blocked the NTP binding site. In support of this conclusion, [14C]captan was observed to bind to the beta subunit which contains the NTP binding site. Whereas, preincubation of RNA polymerase with both DNA and NTPs prevented captan inhibition, preincubation with either DNA or NTPs alone was insufficient to protect the enzyme from the action of captan. Furthermore, the interaction of [14C]captan with the beta and beta' subunits was not prevented by a similar preincubation. Captan also bound, to a lesser extent, to the alpha and sigma subunits. Therefore, captan binding appears to involve interaction with RNA polymerase at sites in addition to those for DNA and NTP; however, this action does not inhibit the polymerase activity.", "contents": "Inhibition of RNA polymerase by captan at both DNA and substrate binding sites. RNA synthesis carried out in vitro by Escherichia coli RNA polymerase was inhibited irreversibly by captan when T7 DNA was used as template. An earlier report and this one show that captan blocks the DNA binding site on the enzyme. Herein, it is also revealed that captan acts at the nucleoside triphosphate (NTP) binding site, and kinetic relationships of the action of captan at the two sites are detailed. The inhibition by captan via the DNA binding site of the enzyme was confirmed by kinetic studies and it was further shown that [14C]captan bound to the beta' subunit of RNA polymerase. This subunit contains the DNA binding site. Competitive-like inhibition by captan versus UTP led to the conclusion that captan also blocked the NTP binding site. In support of this conclusion, [14C]captan was observed to bind to the beta subunit which contains the NTP binding site. Whereas, preincubation of RNA polymerase with both DNA and NTPs prevented captan inhibition, preincubation with either DNA or NTPs alone was insufficient to protect the enzyme from the action of captan. Furthermore, the interaction of [14C]captan with the beta and beta' subunits was not prevented by a similar preincubation. Captan also bound, to a lesser extent, to the alpha and sigma subunits. Therefore, captan binding appears to involve interaction with RNA polymerase at sites in addition to those for DNA and NTP; however, this action does not inhibit the polymerase activity."} {"id": "PMID:1282006", "title": "[The effect of chemical modification on the immunochemical activity of Rm-III neurotoxin from the anemone Radiantus macrodactylus].", "content": "A chemical modification was used for studying the organization of antigenic determinants of neurotoxin Rm-III from the sea anemone Radianthus macrodactylus. Immunochemical experiments were performed using competitive enzyme-linked immunosorbent assay (ELISA) with polyclonal antibodies to Rm-III. The modification affected N-terminal amino group of Gly1, Lys4, Arg13, Trp30 residues, a residue in the Lys46-Lys47-Lys48 sequence, two different residues in the Asp6-Asp7-Glu8 sequence in two samples of the toxin, and two disulphide bonds. Only the modification of the disulphide bonds led to a considerable change in the toxin's affinity to antibodies. The modification of Trp30 resulted in two-fold decrease of the toxin concentration necessary for 50% inhibition of the test-system, whereas upon modification of any other amino acid residue this concentration increased but not more than by 2.2 times. It is suggested that Rm-III sequence lacks individual residues which are of great importance for the toxin's antigenic activity, its conformation being of vital importance for the formation of the toxin's antigenic determinants.", "contents": "[The effect of chemical modification on the immunochemical activity of Rm-III neurotoxin from the anemone Radiantus macrodactylus]. A chemical modification was used for studying the organization of antigenic determinants of neurotoxin Rm-III from the sea anemone Radianthus macrodactylus. Immunochemical experiments were performed using competitive enzyme-linked immunosorbent assay (ELISA) with polyclonal antibodies to Rm-III. The modification affected N-terminal amino group of Gly1, Lys4, Arg13, Trp30 residues, a residue in the Lys46-Lys47-Lys48 sequence, two different residues in the Asp6-Asp7-Glu8 sequence in two samples of the toxin, and two disulphide bonds. Only the modification of the disulphide bonds led to a considerable change in the toxin's affinity to antibodies. The modification of Trp30 resulted in two-fold decrease of the toxin concentration necessary for 50% inhibition of the test-system, whereas upon modification of any other amino acid residue this concentration increased but not more than by 2.2 times. It is suggested that Rm-III sequence lacks individual residues which are of great importance for the toxin's antigenic activity, its conformation being of vital importance for the formation of the toxin's antigenic determinants."} {"id": "PMID:1282007", "title": "The intrinsic migratory capacity of memory T cells contributes to their accumulation in rheumatoid synovium.", "content": "Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites. The characteristics of in vivo migrating cells were studied by dual-immunofluorescence FACS (fluorescence-activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed. Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA-, CD29bright, CD11abright, L-selectin-, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA-DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA-DR and VLA-1. RA synovial lymphocytes exhibited a 2-3-fold increase in migratory capacity over normal and RA PBTL: These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29bright, CD11abright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L-selectin-. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium.", "contents": "The intrinsic migratory capacity of memory T cells contributes to their accumulation in rheumatoid synovium. Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites. The characteristics of in vivo migrating cells were studied by dual-immunofluorescence FACS (fluorescence-activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed. Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA-, CD29bright, CD11abright, L-selectin-, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA-DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA-DR and VLA-1. RA synovial lymphocytes exhibited a 2-3-fold increase in migratory capacity over normal and RA PBTL: These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29bright, CD11abright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L-selectin-. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium."} {"id": "PMID:1282008", "title": "Inhibition of synovial fluid T cell proliferation by anti-CD5 monoclonal antibodies. A potential mechanism for their immunotherapeutic action in vivo.", "content": "Monoclonal antibodies (MAb) directed against the T cell surface molecule CD5 are able to provide accessory stimulatory signals to resting T cells. The potential role of CD5 as an immunoregulatory molecule in inflammatory synovitis was examined. Synovial fluid and peripheral blood T cells of patients with active rheumatoid arthritis (RA) were purified and stimulated with interleukin-2 (IL-2), and the effect of MAb directed against CD5 on IL-2 responsiveness was examined. IL-2-induced proliferation of synovial fluid T cells was strongly inhibited by anti-CD5 MAb, but not by anti-CD28 or anti-CD3 MAb. In RA peripheral blood T cells, MAb directed against CD5, CD3, and CD28 induced IL-2-dependent T cell growth, similar to findings in healthy controls. The difference in activity of anti-CD5 MAb on synovial fluid T cells compared with peripheral blood T cells was not due to different surface expression of CD5. Anti-CD5 has an inhibitory effect on in vivo-activated synovial fluid T cells. The disease-ameliorative effects of anti-CD5 immunotoxin treatment of RA may be partly due to \"switching-off\" of T cell activation in the joints.", "contents": "Inhibition of synovial fluid T cell proliferation by anti-CD5 monoclonal antibodies. A potential mechanism for their immunotherapeutic action in vivo. Monoclonal antibodies (MAb) directed against the T cell surface molecule CD5 are able to provide accessory stimulatory signals to resting T cells. The potential role of CD5 as an immunoregulatory molecule in inflammatory synovitis was examined. Synovial fluid and peripheral blood T cells of patients with active rheumatoid arthritis (RA) were purified and stimulated with interleukin-2 (IL-2), and the effect of MAb directed against CD5 on IL-2 responsiveness was examined. IL-2-induced proliferation of synovial fluid T cells was strongly inhibited by anti-CD5 MAb, but not by anti-CD28 or anti-CD3 MAb. In RA peripheral blood T cells, MAb directed against CD5, CD3, and CD28 induced IL-2-dependent T cell growth, similar to findings in healthy controls. The difference in activity of anti-CD5 MAb on synovial fluid T cells compared with peripheral blood T cells was not due to different surface expression of CD5. Anti-CD5 has an inhibitory effect on in vivo-activated synovial fluid T cells. The disease-ameliorative effects of anti-CD5 immunotoxin treatment of RA may be partly due to \"switching-off\" of T cell activation in the joints."} {"id": "PMID:1282009", "title": "Antilactoferrin antibodies in patients with rheumatoid arthritis are associated with vasculitis.", "content": "To determine the occurrence of antineutrophil cytoplasmic antibodies (ANCA) and the specificity of these antibodies (Ab) in serum from patients with rheumatoid arthritis (RA) and patients with rheumatoid arthritis complicated by vasculitis (rheumatoid vasculitis [RV]). ANCA was detected with an indirect immunofluorescence test on ethanol-fixed granulocytes. Ab against the cytoplasmic antigens proteinase-3, elastase, lactoferrin (LF), and myeloperoxidase were measured by enzyme-linked immunosorbent assay. ANCA were found in the serum of 43% of 49 patients with RV and in 36% of 50 patients with RA. Anti-LF Ab occurred more frequently in RV patients (45%) than in RA patients (4%), whereas reactivity against the other cytoplasmic antigens did not differe significantly between these groups. Anti-LF Ab in serum of patients with RA may be useful in the diagnosis of vasculitis in RA.", "contents": "Antilactoferrin antibodies in patients with rheumatoid arthritis are associated with vasculitis. To determine the occurrence of antineutrophil cytoplasmic antibodies (ANCA) and the specificity of these antibodies (Ab) in serum from patients with rheumatoid arthritis (RA) and patients with rheumatoid arthritis complicated by vasculitis (rheumatoid vasculitis [RV]). ANCA was detected with an indirect immunofluorescence test on ethanol-fixed granulocytes. Ab against the cytoplasmic antigens proteinase-3, elastase, lactoferrin (LF), and myeloperoxidase were measured by enzyme-linked immunosorbent assay. ANCA were found in the serum of 43% of 49 patients with RV and in 36% of 50 patients with RA. Anti-LF Ab occurred more frequently in RV patients (45%) than in RA patients (4%), whereas reactivity against the other cytoplasmic antigens did not differe significantly between these groups. Anti-LF Ab in serum of patients with RA may be useful in the diagnosis of vasculitis in RA."} {"id": "PMID:1282010", "title": "Effect of miltefosine on transplanted methylnitrosourea-induced mammary carcinoma growing in Fischer 344 rats.", "content": "Miltefosine (hexadecylphosphocholine, HPC, CAS 58066-85-6) was investigated in transplanted primary methylnitrosourea-induced PYH mammary carcinoma of F344 rats. The therapy was performed in the 5th and 10th passage. At first HPC (113 mg/kg body weight) significantly reduced the median tumor volume, but a loss of activity was observed in the 10th passage. To explain the loss of sensitivity and to obtain information on the mechanism of action histology, cytoskeleton and hormone receptor content were investigated. The most important change was observed in the histopathology of the tumor. The initial tubular papillary adenocarcinoma was transformed into a malignant adenoacanthoma with epithelial structure. Vimentin as an endothelial marker of the cytoskeleton was equally expressed in all passages. Cytokeratin was weakly expressed in the earlier passages and intensively present in the late passages. The histopathological change from tubular adenocarcinoma to malignant adenoacanthoma might be caused by an overgrowth of the primary epithelial tumor cells or by a real transformation in the morphological characteristics of the tumor, which may occur during repeated transplantation.", "contents": "Effect of miltefosine on transplanted methylnitrosourea-induced mammary carcinoma growing in Fischer 344 rats. Miltefosine (hexadecylphosphocholine, HPC, CAS 58066-85-6) was investigated in transplanted primary methylnitrosourea-induced PYH mammary carcinoma of F344 rats. The therapy was performed in the 5th and 10th passage. At first HPC (113 mg/kg body weight) significantly reduced the median tumor volume, but a loss of activity was observed in the 10th passage. To explain the loss of sensitivity and to obtain information on the mechanism of action histology, cytoskeleton and hormone receptor content were investigated. The most important change was observed in the histopathology of the tumor. The initial tubular papillary adenocarcinoma was transformed into a malignant adenoacanthoma with epithelial structure. Vimentin as an endothelial marker of the cytoskeleton was equally expressed in all passages. Cytokeratin was weakly expressed in the earlier passages and intensively present in the late passages. The histopathological change from tubular adenocarcinoma to malignant adenoacanthoma might be caused by an overgrowth of the primary epithelial tumor cells or by a real transformation in the morphological characteristics of the tumor, which may occur during repeated transplantation."} {"id": "PMID:1282011", "title": "Humoral responses to the immunodominant gag and env epitopes of human T-lymphotropic virus type I among Melanesians.", "content": "The immune responsiveness to the immunodominant B-cell epitopes of human T-lymphotropic virus type I (HTLV-I), derived from the external envelope glycoprotein (recombinant MTA-1(162-209), synthetic Env-1(194-214), and Env-5(242-257)) and the gag-encoded matrix protein (Gag-1a(102-117)), was analyzed in 19 HTLV-I-seropositive and 51 HTLV I-seroindeterminate Melanesians from Papua New Guinea and the Solomon Islands. The reactivities of seropositive Melanesian specimens to MTA-1 (100%), Env-5 (89%), and Gag-1a (79%) were similar to that seen with U.S. specimens, while reactivity to Env-1 was lower in Melanesian specimens (68%). Minimal reactivity was found to the env epitopes among the 51 HTLV-I-seroindeterminate Melanesians, but 29 (57%) reacted to Gag-1a. The failure to detect HTLV-I gag, pol, env, and tax gene sequences by polymerase chain reaction among the seroindeterminate Melanesians suggests that such reactivities to the Gag-1a epitope represent cross-reacting antibodies with closely related microbial or cellular proteins.", "contents": "Humoral responses to the immunodominant gag and env epitopes of human T-lymphotropic virus type I among Melanesians. The immune responsiveness to the immunodominant B-cell epitopes of human T-lymphotropic virus type I (HTLV-I), derived from the external envelope glycoprotein (recombinant MTA-1(162-209), synthetic Env-1(194-214), and Env-5(242-257)) and the gag-encoded matrix protein (Gag-1a(102-117)), was analyzed in 19 HTLV-I-seropositive and 51 HTLV I-seroindeterminate Melanesians from Papua New Guinea and the Solomon Islands. The reactivities of seropositive Melanesian specimens to MTA-1 (100%), Env-5 (89%), and Gag-1a (79%) were similar to that seen with U.S. specimens, while reactivity to Env-1 was lower in Melanesian specimens (68%). Minimal reactivity was found to the env epitopes among the 51 HTLV-I-seroindeterminate Melanesians, but 29 (57%) reacted to Gag-1a. The failure to detect HTLV-I gag, pol, env, and tax gene sequences by polymerase chain reaction among the seroindeterminate Melanesians suggests that such reactivities to the Gag-1a epitope represent cross-reacting antibodies with closely related microbial or cellular proteins."} {"id": "PMID:1282012", "title": "Antibody-dependent cellular cytotoxicity (ADCC) is directed against immunodominant epitopes of the envelope proteins of human immunodeficiency virus 1 (HIV-1).", "content": "In this study, epitopes of HIV envelope proteins that are involved in ADCC were identified. Peripheral blood mononuclear cells (PBMC) were obtained from adults with asymptomatic HIV infection or early symptoms of AIDS. These PBMC, which were reported to be \"armed\" in vivo with HIV-specific antibodies, were used as effector cells in 51Cr release assays. Target cells consisted of CD4 lymphocytes from healthy seronegative donors, coated with the IIIB strain of HIV-1 or with one of seven synthetic peptides. Cytotoxicity was detected against CD4 lymphocytes coated with HIV-1 IIIB or with the peptides env aa 507-518, corresponding to the carboxy-terminus of gp120, and env aa 597-611, corresponding to the region of the cysteine loop of gp41. The magnitude of target cell lysis was directly related to the quantity of peptide used. In contrast, target cells coated with the peptide gag aa 129-135, corresponding to the p17/p24 cleavage region of the gag precursor, were not killed. The same immunodominant regions which were involved in ADCC were recognized in enzyme-linked immunoabsorbent assays (ELISA) by the majority of 107 sera from HIV-infected adults. We conclude that the immunodominant epitopes located at the carboxy-terminus of gp120 and the cysteine loop of gp41 serve as recognition structure for antibodies, capable of mediating ADCC against HIV-infected cells.", "contents": "Antibody-dependent cellular cytotoxicity (ADCC) is directed against immunodominant epitopes of the envelope proteins of human immunodeficiency virus 1 (HIV-1). In this study, epitopes of HIV envelope proteins that are involved in ADCC were identified. Peripheral blood mononuclear cells (PBMC) were obtained from adults with asymptomatic HIV infection or early symptoms of AIDS. These PBMC, which were reported to be \"armed\" in vivo with HIV-specific antibodies, were used as effector cells in 51Cr release assays. Target cells consisted of CD4 lymphocytes from healthy seronegative donors, coated with the IIIB strain of HIV-1 or with one of seven synthetic peptides. Cytotoxicity was detected against CD4 lymphocytes coated with HIV-1 IIIB or with the peptides env aa 507-518, corresponding to the carboxy-terminus of gp120, and env aa 597-611, corresponding to the region of the cysteine loop of gp41. The magnitude of target cell lysis was directly related to the quantity of peptide used. In contrast, target cells coated with the peptide gag aa 129-135, corresponding to the p17/p24 cleavage region of the gag precursor, were not killed. The same immunodominant regions which were involved in ADCC were recognized in enzyme-linked immunoabsorbent assays (ELISA) by the majority of 107 sera from HIV-infected adults. We conclude that the immunodominant epitopes located at the carboxy-terminus of gp120 and the cysteine loop of gp41 serve as recognition structure for antibodies, capable of mediating ADCC against HIV-infected cells."} {"id": "PMID:1282013", "title": "Basal forebrain neurons and memory: a biochemical, histological, and behavioral study of differential vulnerability to ibotenate and quisqualate.", "content": "The differential vulnerability of basal forebrain cells to ibotenate (IBO) or quisqualate (QUIS) was investigated in rats. IBO was also coinjected with cystine (CYS) or zinc (Zn). Cortical choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) activity, neurotensin receptors, and high-affinity choline uptake sites were quantified in conjunction with radioimmunoassays for neurotensin, substance P, and somatostatin; immunocytochemistry for neurotensin-, somatostatin-, Leu-enkephalin-, and ChAT-positive cells; and in situ hybridization histochemistry of somatostatin, substance P, and enkephalin mRNAs. Compared with the performance of controls, continuous alternation performance in a T maze of IBO+Zn or IBO+CYS rats was better than that of IBO rats, whereas the performance of QUIS rats was unimpaired. Of those neurotransmitter systems examined, only ChAT-immunoreactive cells were vulnerable to IBO or QUIS. However, cholinergic cell loss did not correlate with impaired performance.", "contents": "Basal forebrain neurons and memory: a biochemical, histological, and behavioral study of differential vulnerability to ibotenate and quisqualate. The differential vulnerability of basal forebrain cells to ibotenate (IBO) or quisqualate (QUIS) was investigated in rats. IBO was also coinjected with cystine (CYS) or zinc (Zn). Cortical choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) activity, neurotensin receptors, and high-affinity choline uptake sites were quantified in conjunction with radioimmunoassays for neurotensin, substance P, and somatostatin; immunocytochemistry for neurotensin-, somatostatin-, Leu-enkephalin-, and ChAT-positive cells; and in situ hybridization histochemistry of somatostatin, substance P, and enkephalin mRNAs. Compared with the performance of controls, continuous alternation performance in a T maze of IBO+Zn or IBO+CYS rats was better than that of IBO rats, whereas the performance of QUIS rats was unimpaired. Of those neurotransmitter systems examined, only ChAT-immunoreactive cells were vulnerable to IBO or QUIS. However, cholinergic cell loss did not correlate with impaired performance."} {"id": "PMID:1282014", "title": "Biochemical and behavioral effects of a sensorimotor cortex injury in rats pretreated with the noradrenergic neurotoxin DSP-4.", "content": "The role of the noradrenergic (NE) system in recovery of motor function after sensorimotor cortex (SMCX) injury was investigated. After training on a beam-walking task to assess changes in motor function, animals were given DSP-4 or saline and tested for 2 weeks; both groups then received unilateral SMCX suction ablations. Animals that received DSP-4 were significantly retarded in motor recovery compared with the saline group. At 24 days after injury (after motor recovery), the animals' deficits were significantly reinstated with NE-blocking drugs. DSP-4 significantly depressed NE levels in the hippocampus and cerebellum. A Timm histochemical analysis revealed glutamatergic sprouting in the hippocampus of animals that were pretreated with DSP-4, which suggests the possibility that similar glutamatergic plasticity in other pathways may occur and that excitotoxicity might also play a role after the DSP-4 induced NE deafferentation.", "contents": "Biochemical and behavioral effects of a sensorimotor cortex injury in rats pretreated with the noradrenergic neurotoxin DSP-4. The role of the noradrenergic (NE) system in recovery of motor function after sensorimotor cortex (SMCX) injury was investigated. After training on a beam-walking task to assess changes in motor function, animals were given DSP-4 or saline and tested for 2 weeks; both groups then received unilateral SMCX suction ablations. Animals that received DSP-4 were significantly retarded in motor recovery compared with the saline group. At 24 days after injury (after motor recovery), the animals' deficits were significantly reinstated with NE-blocking drugs. DSP-4 significantly depressed NE levels in the hippocampus and cerebellum. A Timm histochemical analysis revealed glutamatergic sprouting in the hippocampus of animals that were pretreated with DSP-4, which suggests the possibility that similar glutamatergic plasticity in other pathways may occur and that excitotoxicity might also play a role after the DSP-4 induced NE deafferentation."} {"id": "PMID:1282015", "title": "HIV-1 biological phenotype and the development of zidovudine resistance in relation to disease progression in asymptomatic individuals during treatment.", "content": "To determine which parameters are associated with clinical progression during zidovudine treatment of asymptomatic HIV-1-infected individuals. Twenty-four initially asymptomatic HIV-1-infected individuals were treated with zidovudine and followed until the development of AIDS or for approximately 3 years. HIV-1 phenotype was determined by cocultivation of patient cells with donor lymphocytes, and by a new assay of direct cocultivation with MT-2 cells. Specific mutations in the HIV-1 reverse transcriptase (RT) gene conferring resistance to zidovudine were detected using a selective polymerase chain reaction. Progression to AIDS was more rapid in individuals harbouring syncytium-inducing (SI) viral isolates or showing a conversion from non-syncytium-inducing (NSI) to SI viral isolates. One out of 20 patients who spent a total of 559 months harbouring an NSI phenotype progressed to AIDS, whereas eight out of 12 patients who spent a total of 223 months harbouring an SI phenotype progressed to AIDS (P < 0.001). There was no significant difference between SI and non-SI isolates in the frequency of five mutations causing zidovudine resistance. However, all SI isolates obtained after 2 years of treatment contained mutations in codons 41 and 215 of the RT gene, whereas only five out of 11 (45%) NSI isolates obtained at that time had this combination of mutations. Conversion to the SI phenotype cannot be prevented by zidovudine treatment. The presence or appearance of an SI virus heralded disease progression in zidovudine-treated individuals. Further research is required to investigate the relationship between virus phenotype and development of zidovudine resistance.", "contents": "HIV-1 biological phenotype and the development of zidovudine resistance in relation to disease progression in asymptomatic individuals during treatment. To determine which parameters are associated with clinical progression during zidovudine treatment of asymptomatic HIV-1-infected individuals. Twenty-four initially asymptomatic HIV-1-infected individuals were treated with zidovudine and followed until the development of AIDS or for approximately 3 years. HIV-1 phenotype was determined by cocultivation of patient cells with donor lymphocytes, and by a new assay of direct cocultivation with MT-2 cells. Specific mutations in the HIV-1 reverse transcriptase (RT) gene conferring resistance to zidovudine were detected using a selective polymerase chain reaction. Progression to AIDS was more rapid in individuals harbouring syncytium-inducing (SI) viral isolates or showing a conversion from non-syncytium-inducing (NSI) to SI viral isolates. One out of 20 patients who spent a total of 559 months harbouring an NSI phenotype progressed to AIDS, whereas eight out of 12 patients who spent a total of 223 months harbouring an SI phenotype progressed to AIDS (P < 0.001). There was no significant difference between SI and non-SI isolates in the frequency of five mutations causing zidovudine resistance. However, all SI isolates obtained after 2 years of treatment contained mutations in codons 41 and 215 of the RT gene, whereas only five out of 11 (45%) NSI isolates obtained at that time had this combination of mutations. Conversion to the SI phenotype cannot be prevented by zidovudine treatment. The presence or appearance of an SI virus heralded disease progression in zidovudine-treated individuals. Further research is required to investigate the relationship between virus phenotype and development of zidovudine resistance."} {"id": "PMID:1282016", "title": "An Algerian child homozygous for the M470V polymorphism and for a deletion of two nucleotides in exon 10 of the CFTR gene, shows severe cystic fibrosis symptoms.", "content": "When screening for the presence of major cystic fibrosis mutations in Algerian cystic fibrosis families by heteroduplex formation, aberrant heteroduplexes were observed for exon 10 in one family. Here we describe the clinical and molecular findings in a severely affected child of this family, homozygous for the 1609delCA and for the M470V polymorphism.", "contents": "An Algerian child homozygous for the M470V polymorphism and for a deletion of two nucleotides in exon 10 of the CFTR gene, shows severe cystic fibrosis symptoms. When screening for the presence of major cystic fibrosis mutations in Algerian cystic fibrosis families by heteroduplex formation, aberrant heteroduplexes were observed for exon 10 in one family. Here we describe the clinical and molecular findings in a severely affected child of this family, homozygous for the 1609delCA and for the M470V polymorphism."} {"id": "PMID:1282017", "title": "Techniques for studies on growth characteristics of human prostatic cancer cells.", "content": "The methods described in this article seem to be useful for studies on the growth characteristics of malignant epithelial prostate cells which are still under the influence of healthy cells. Before establishing primary cultures, pieces of tissue were sectioned in such a way that they could be unfolded to obtain a large surface. These pieces were treated enzymatically and then incubated for at least 4-6 weeks. In this time, cells grew or migrated out of the tissue and spread over the surface of the culture flasks. The viable single cells harvested from these primary cultures were characterized flow cytometrically, fractionated by countercurrent centrifugal elutriation, or further incubated above agarose so that they formed three-dimensional spheroids. Cytometric determinations of cellular cytokeratin, vimentin, and DNA were performed before and after incubation. They suggested that the percentages of cytokeratin-positive (epithelial) cells, vimentin-positive cells (fibroblasts), and aneuploid cells remained at levels (in vitro) similar to those within the pieces of tissue used for the culturing experiments, respectively. Since our culture technique allows the propagation of human epithelial prostate cells in vitro as they would grow in vivo under the control of the surrounding tissue, the method should help to investigate which particular treatment of the cells influences the growth of the malignant cells, while they are still surrounded by other cells of the same prostatic organ.", "contents": "Techniques for studies on growth characteristics of human prostatic cancer cells. The methods described in this article seem to be useful for studies on the growth characteristics of malignant epithelial prostate cells which are still under the influence of healthy cells. Before establishing primary cultures, pieces of tissue were sectioned in such a way that they could be unfolded to obtain a large surface. These pieces were treated enzymatically and then incubated for at least 4-6 weeks. In this time, cells grew or migrated out of the tissue and spread over the surface of the culture flasks. The viable single cells harvested from these primary cultures were characterized flow cytometrically, fractionated by countercurrent centrifugal elutriation, or further incubated above agarose so that they formed three-dimensional spheroids. Cytometric determinations of cellular cytokeratin, vimentin, and DNA were performed before and after incubation. They suggested that the percentages of cytokeratin-positive (epithelial) cells, vimentin-positive cells (fibroblasts), and aneuploid cells remained at levels (in vitro) similar to those within the pieces of tissue used for the culturing experiments, respectively. Since our culture technique allows the propagation of human epithelial prostate cells in vitro as they would grow in vivo under the control of the surrounding tissue, the method should help to investigate which particular treatment of the cells influences the growth of the malignant cells, while they are still surrounded by other cells of the same prostatic organ."} {"id": "PMID:1282020", "title": "A T-helper cell epitope overlaps a major B-cell epitope in human papillomavirus type 18 E2 protein.", "content": "Cultivated CD4+ T-helper cells from two patients with cervical adenocarcinoma showed responses to a peptide EKTGILTVTYHSETQRTK derived from an E2 protein of human papillomavirus type 18 (HPV 18), but not to a corresponding HPV 16 peptide (HKSAIVTLTYDSEWQRDQ). Serum antibodies in the HPV 18 peptide were also demonstrated in these patients. The GILT motif resembles a common pattern present in many T-cell epitopes, and is located at the beginning of an 11-amino acid-long A-helix structure close to the carboxyterminal end of HPV 18 E2. We conclude that two epitopes (a T-helper cell epitope and a B-cell epitope) overlap in the HPV 18 E2.", "contents": "A T-helper cell epitope overlaps a major B-cell epitope in human papillomavirus type 18 E2 protein. Cultivated CD4+ T-helper cells from two patients with cervical adenocarcinoma showed responses to a peptide EKTGILTVTYHSETQRTK derived from an E2 protein of human papillomavirus type 18 (HPV 18), but not to a corresponding HPV 16 peptide (HKSAIVTLTYDSEWQRDQ). Serum antibodies in the HPV 18 peptide were also demonstrated in these patients. The GILT motif resembles a common pattern present in many T-cell epitopes, and is located at the beginning of an 11-amino acid-long A-helix structure close to the carboxyterminal end of HPV 18 E2. We conclude that two epitopes (a T-helper cell epitope and a B-cell epitope) overlap in the HPV 18 E2."} {"id": "PMID:1282018", "title": "Dextran retention in the rat brain following release from a polymer implant.", "content": "Intracranial controlled release polymers may improve drug administration to the brain, where therapy is frequently limited due to the low permeability of brain capillaries to therapeutic agents. On the basis of drug transport and elimination rates, we proposed that high molecular weight, water-soluble molecules would be retained in the brain space following release from an intracranial implant. To test this hypothesis, solid particles of different molecular weight fractions of fluorescein isothiocyanate labeled dextran (FITC-dextran; 4 x 10(3) Da (4 kDa) < weight-averaged molecular weight (Mw) < 150 kDa) or fluorescein were uniformly dispersed in matrices of a polyanhydride copolymer synthesized from a fatty acid dimer and sebacic acid in a 50:50 ratio, P(FAD:SA). When incubated in buffered saline, FITC-dextran fractions of 70 kDa Mw were released from the polymer within 48 h; 4 kDa Mw FITC-dextran and fluorescein were released more slowly. Following implantation of P(FAD:SA) matrices containing either 70 kDa Mw FITC-dextran, 4 kDa Mw FITC-dextran, or fluorescein into the brains of normal rats, fluorescent tracers were continuously released into the brain tissue for 30 days. Tracer concentrations within the brain were significantly higher for large molecular weight tracers (70 kDa Mw FITC-dextran >> 4 kDa Mw FITC-dextran > fluorescein). The rate of elimination, kapp, of each tracer from the brain was determined by comparing experimental data with a model describing tracer diffusion/elimination in the brain extracellular space; kapp decreased with increasing molecular weight (fluorescein > 4 kDa Mw FITC-dextran > 70 kDa Mw FITC-dextran).", "contents": "Dextran retention in the rat brain following release from a polymer implant. Intracranial controlled release polymers may improve drug administration to the brain, where therapy is frequently limited due to the low permeability of brain capillaries to therapeutic agents. On the basis of drug transport and elimination rates, we proposed that high molecular weight, water-soluble molecules would be retained in the brain space following release from an intracranial implant. To test this hypothesis, solid particles of different molecular weight fractions of fluorescein isothiocyanate labeled dextran (FITC-dextran; 4 x 10(3) Da (4 kDa) < weight-averaged molecular weight (Mw) < 150 kDa) or fluorescein were uniformly dispersed in matrices of a polyanhydride copolymer synthesized from a fatty acid dimer and sebacic acid in a 50:50 ratio, P(FAD:SA). When incubated in buffered saline, FITC-dextran fractions of 70 kDa Mw were released from the polymer within 48 h; 4 kDa Mw FITC-dextran and fluorescein were released more slowly. Following implantation of P(FAD:SA) matrices containing either 70 kDa Mw FITC-dextran, 4 kDa Mw FITC-dextran, or fluorescein into the brains of normal rats, fluorescent tracers were continuously released into the brain tissue for 30 days. Tracer concentrations within the brain were significantly higher for large molecular weight tracers (70 kDa Mw FITC-dextran >> 4 kDa Mw FITC-dextran > fluorescein). The rate of elimination, kapp, of each tracer from the brain was determined by comparing experimental data with a model describing tracer diffusion/elimination in the brain extracellular space; kapp decreased with increasing molecular weight (fluorescein > 4 kDa Mw FITC-dextran > 70 kDa Mw FITC-dextran)."} {"id": "PMID:1282021", "title": "Expression of cytokeratin and erbB-2 oncoprotein in Paget's disease of the nipple. An immunohistochemical study.", "content": "The occurrence of epithelial membrane antigen (EMA), low molecular weight cytokeratin (CK) and erbB-2 oncoprotein was investigated in twenty-eight cases of Paget's disease of the nipple (PD) to determine their diagnostic usefulness. The ABC technique with monoclonal antibodies was used on formalin-fixed, paraffin-embedded tissue. The Paget's cells showed positive immunoreactivity for all three antigens investigated in a high percentage of PD. Immunoreactivity for CK and erbB-2 oncoprotein was restricted to the Paget's cells, whereas EMA in some cases also stained the adjacent keratinocytes. Since CK and/or erbB-2 oncoprotein occurred in 93% of the cases, we conclude that demonstration of both antigens is useful in the diagnosis of PD. ErbB-2 oncoprotein was also found to be expressed in a high percentage of the underlying intraductal and invasive carcinomas.", "contents": "Expression of cytokeratin and erbB-2 oncoprotein in Paget's disease of the nipple. An immunohistochemical study. The occurrence of epithelial membrane antigen (EMA), low molecular weight cytokeratin (CK) and erbB-2 oncoprotein was investigated in twenty-eight cases of Paget's disease of the nipple (PD) to determine their diagnostic usefulness. The ABC technique with monoclonal antibodies was used on formalin-fixed, paraffin-embedded tissue. The Paget's cells showed positive immunoreactivity for all three antigens investigated in a high percentage of PD. Immunoreactivity for CK and erbB-2 oncoprotein was restricted to the Paget's cells, whereas EMA in some cases also stained the adjacent keratinocytes. Since CK and/or erbB-2 oncoprotein occurred in 93% of the cases, we conclude that demonstration of both antigens is useful in the diagnosis of PD. ErbB-2 oncoprotein was also found to be expressed in a high percentage of the underlying intraductal and invasive carcinomas."} {"id": "PMID:1282019", "title": "Altered distribution of mitochondria and actin fibers in 3T3 cells cultured on microcarriers.", "content": "The mitochondria and actin fibers of 3T3 fibroblasts cultured on microcarriers in spinner flasks were visualized using fluorescent stains. In contrast to cells grown on planar surfaces under static or steady laminar flow conditions, cells exposed to higher levels of turbulent agitation do not form actin stress fibers. Greater agitation also leads to a more diffuse appearance of the mitochondria and a wider distribution of them throughout the cytoplasm. This response may indicate damaged mitochondria, as similar results have been reported for chemical toxins.", "contents": "Altered distribution of mitochondria and actin fibers in 3T3 cells cultured on microcarriers. The mitochondria and actin fibers of 3T3 fibroblasts cultured on microcarriers in spinner flasks were visualized using fluorescent stains. In contrast to cells grown on planar surfaces under static or steady laminar flow conditions, cells exposed to higher levels of turbulent agitation do not form actin stress fibers. Greater agitation also leads to a more diffuse appearance of the mitochondria and a wider distribution of them throughout the cytoplasm. This response may indicate damaged mitochondria, as similar results have been reported for chemical toxins."} {"id": "PMID:1282022", "title": "Epitope homology between bacterial heat shock protein and self-proteins in the host cell.", "content": "Mouse monoclonal antibodies (MAbs) showing distinct reactivity against the 60-kilodalton (kDa) antigen heat shock protein of Yersinia enterocolitica, designated cross-reacting protein antigen (CRPA), have previously been established. The reactivities of these MAbs (5C3 and 3C8) against mouse and human host cells were studied by Western blotting and flow cytometric analysis. The results indicated that epitopes on the bacterial 60-kDa heat shock protein are present on various molecules in mouse spleen cells and human B cells. An epitope recognized by MAb 5C3 was expressed on the mouse and human host cell surface, and an epitope recognized by MAb 3C8 was also expressed on the human host cell surface.", "contents": "Epitope homology between bacterial heat shock protein and self-proteins in the host cell. Mouse monoclonal antibodies (MAbs) showing distinct reactivity against the 60-kilodalton (kDa) antigen heat shock protein of Yersinia enterocolitica, designated cross-reacting protein antigen (CRPA), have previously been established. The reactivities of these MAbs (5C3 and 3C8) against mouse and human host cells were studied by Western blotting and flow cytometric analysis. The results indicated that epitopes on the bacterial 60-kDa heat shock protein are present on various molecules in mouse spleen cells and human B cells. An epitope recognized by MAb 5C3 was expressed on the mouse and human host cell surface, and an epitope recognized by MAb 3C8 was also expressed on the human host cell surface."} {"id": "PMID:1282023", "title": "The third IGF-II promoter specifies transcription of three transcripts out of five in human placenta.", "content": "Insulin-like growth factor-II (IGF-II) mRNA exists as multiple transcript size classes, such as 6.0, 5.3, 4.9, 3.2, and 2.2 kb mRNAs in various human tissues. Three different promoters, 2 different polyadenylation sites, and alternative splicing are involved in producing these multiple transcripts. Initiation of transcription at the 3 different promoters results in multiple mRNAs which contain identical coding regions but different 5'-untranslated regions (5'-UTRs). The first promoter is thought to direct expression of 5.3 kb mRNA in adult human liver. The second promoter region directs expression of 6.0, 3.2, and 2.2 kb mRNAs in human fetal tissues and several adult nonliver tissues. The third promoter specifies transcription of a 4.9 kb mRNA in various tissues. We isolated and sequenced a cDNA clone (pIGF-II-1-70) from a human placental cDNA library, which contains the IGF-II coding region and the 5'-UTR associated with the third promoter. By using a 5'-UTR-specific probe from the clone, we found that this third 5'-UTR is contained in the IGF-II mRNA of 2.2 kb and is absent in the 3.2 kb IGF-II mRNA. We also found an 0.9 kb transcript expressed in placenta, which hybridized strongly to the third 5'-UTR specific probe but not to IGF-II coding region probes. This finding might indicate the existence of an mRNA encoding an IGF-II-associated peptide.", "contents": "The third IGF-II promoter specifies transcription of three transcripts out of five in human placenta. Insulin-like growth factor-II (IGF-II) mRNA exists as multiple transcript size classes, such as 6.0, 5.3, 4.9, 3.2, and 2.2 kb mRNAs in various human tissues. Three different promoters, 2 different polyadenylation sites, and alternative splicing are involved in producing these multiple transcripts. Initiation of transcription at the 3 different promoters results in multiple mRNAs which contain identical coding regions but different 5'-untranslated regions (5'-UTRs). The first promoter is thought to direct expression of 5.3 kb mRNA in adult human liver. The second promoter region directs expression of 6.0, 3.2, and 2.2 kb mRNAs in human fetal tissues and several adult nonliver tissues. The third promoter specifies transcription of a 4.9 kb mRNA in various tissues. We isolated and sequenced a cDNA clone (pIGF-II-1-70) from a human placental cDNA library, which contains the IGF-II coding region and the 5'-UTR associated with the third promoter. By using a 5'-UTR-specific probe from the clone, we found that this third 5'-UTR is contained in the IGF-II mRNA of 2.2 kb and is absent in the 3.2 kb IGF-II mRNA. We also found an 0.9 kb transcript expressed in placenta, which hybridized strongly to the third 5'-UTR specific probe but not to IGF-II coding region probes. This finding might indicate the existence of an mRNA encoding an IGF-II-associated peptide."} {"id": "PMID:1282024", "title": "Isolation and cultivation of blastocyst-derived stem cell lines from American mink (Mustela vison).", "content": "Ten embryonic stem (ES) cell lines from mink blastocysts were isolated and characterized. All the lines had a normal diploid karyotype; of the ten lines studied, five had the XX and five had the XY constitution. Testing of the pluripotency of the ES-like cells demonstrated that 1) among four lines of genotype XX, and X was late-replicating in three; both Xs were active in about one-third of cells of line MES8, and analysis of glucose-6-phosphate dehydrogenase revealed no dosage compensation for the X-linked gene; 2) when cultured in suspension, the majority of lines were capable of forming \"simple\" embryoid bodies (EB), and two only showed the capacity for forming \"cystic\" multilayer EBs. However, formation of ectoderm or foci of yolk sac hematopoiesis, a feature of mouse ES cells, was not observed in the \"cystic\" EB; 3) when cultured as a monolayer without feeder, the ES cells differentiated into either vimentin-positive fibroblast-like cells or cytokeratin-positive epithelial-like cells (less frequently); neural cells appeared in two lines; 4) when injected into athymic mice, only one of the four tested lines gave rise to tumors. These were fibrosarcomas composed of fibroblast-like cells, with an admixture of smooth muscular elements and stray islets of epithelial tissue; (5) when the ES cells of line MES1 were injected into 102 blastocyst cavities and subsequently transplanted into foster mothers, we obtained 30 offspring. Analysis of the biochemical markers and coat color did not demonstrate the presence of chimaeras among offspring. Thus the cell lines derived from mink blastocysts are true ES cells. However, their pluripotential capacities are restricted.", "contents": "Isolation and cultivation of blastocyst-derived stem cell lines from American mink (Mustela vison). Ten embryonic stem (ES) cell lines from mink blastocysts were isolated and characterized. All the lines had a normal diploid karyotype; of the ten lines studied, five had the XX and five had the XY constitution. Testing of the pluripotency of the ES-like cells demonstrated that 1) among four lines of genotype XX, and X was late-replicating in three; both Xs were active in about one-third of cells of line MES8, and analysis of glucose-6-phosphate dehydrogenase revealed no dosage compensation for the X-linked gene; 2) when cultured in suspension, the majority of lines were capable of forming \"simple\" embryoid bodies (EB), and two only showed the capacity for forming \"cystic\" multilayer EBs. However, formation of ectoderm or foci of yolk sac hematopoiesis, a feature of mouse ES cells, was not observed in the \"cystic\" EB; 3) when cultured as a monolayer without feeder, the ES cells differentiated into either vimentin-positive fibroblast-like cells or cytokeratin-positive epithelial-like cells (less frequently); neural cells appeared in two lines; 4) when injected into athymic mice, only one of the four tested lines gave rise to tumors. These were fibrosarcomas composed of fibroblast-like cells, with an admixture of smooth muscular elements and stray islets of epithelial tissue; (5) when the ES cells of line MES1 were injected into 102 blastocyst cavities and subsequently transplanted into foster mothers, we obtained 30 offspring. Analysis of the biochemical markers and coat color did not demonstrate the presence of chimaeras among offspring. Thus the cell lines derived from mink blastocysts are true ES cells. However, their pluripotential capacities are restricted."} {"id": "PMID:1282025", "title": "Monoclonal antibody AG7 inhibits fertilization post sperm-zona binding.", "content": "Monoclonal antibodies (mAbs) against sperm cells are currently being used in an effort to define spermatozoal antigens involved in the fertilization process. We have produced a number of anti-human sperm mAbs by immunization of female mice with the 100,000 x g supernatant of octylglycoside-solubilized washed human sperm. From a panel of mAbs, 1 antibody, AG7, was selected and characterized due to its fertilization-inhibiting characteristics. MAb AG7 defines a sperm acrosome antigen-1 (SAA-1) located in the acrosomal region of human sperm as evaluated by indirect immunofluorescence. Staining of life sperm cells indicated that the antigen is present on the sperm surface. SAA-1 was also found on sperm of several other mammalian species, implying evolutionary conservation of the antigen. SAA-1 was first observed on testicular sperm and can be followed through epididymal transit, ejaculation, and capacitation. When applied in a mouse in vitro fertilization assay, mAb AG7 inhibits fertilization by greater than 95%, and inhibition is dose dependent, with half-maximal inhibition at 0.8 micrograms/ml. The block to fertilization could not be attributed to sperm agglutination, inhibition of motility, interference with adhesion to the zona pellucida, or inhibition of fusion with the oocyte membrane. MAb AG7 was demonstrated to inhibit calcium influx in spermatozoa in vitro (measured using the fluorescent indicator fura 2), a prerequisite for the acrosome reaction. Initial biochemical characterization of the antigen suggests it is proteinlike in nature, with a molecular weight of approximately 220 kD. The results suggest that SAA-1, identified by mAb AG7, is a sperm antigen crucially involved in the fertilization process, possibly an atypical steroid receptor or ion channel located within the sperm plasma membrane.", "contents": "Monoclonal antibody AG7 inhibits fertilization post sperm-zona binding. Monoclonal antibodies (mAbs) against sperm cells are currently being used in an effort to define spermatozoal antigens involved in the fertilization process. We have produced a number of anti-human sperm mAbs by immunization of female mice with the 100,000 x g supernatant of octylglycoside-solubilized washed human sperm. From a panel of mAbs, 1 antibody, AG7, was selected and characterized due to its fertilization-inhibiting characteristics. MAb AG7 defines a sperm acrosome antigen-1 (SAA-1) located in the acrosomal region of human sperm as evaluated by indirect immunofluorescence. Staining of life sperm cells indicated that the antigen is present on the sperm surface. SAA-1 was also found on sperm of several other mammalian species, implying evolutionary conservation of the antigen. SAA-1 was first observed on testicular sperm and can be followed through epididymal transit, ejaculation, and capacitation. When applied in a mouse in vitro fertilization assay, mAb AG7 inhibits fertilization by greater than 95%, and inhibition is dose dependent, with half-maximal inhibition at 0.8 micrograms/ml. The block to fertilization could not be attributed to sperm agglutination, inhibition of motility, interference with adhesion to the zona pellucida, or inhibition of fusion with the oocyte membrane. MAb AG7 was demonstrated to inhibit calcium influx in spermatozoa in vitro (measured using the fluorescent indicator fura 2), a prerequisite for the acrosome reaction. Initial biochemical characterization of the antigen suggests it is proteinlike in nature, with a molecular weight of approximately 220 kD. The results suggest that SAA-1, identified by mAb AG7, is a sperm antigen crucially involved in the fertilization process, possibly an atypical steroid receptor or ion channel located within the sperm plasma membrane."} {"id": "PMID:1282026", "title": "Semiquantitative analysis of X-linked gene expression during spermatogenesis in the mouse: ethidium-bromide staining of RT-PCR products.", "content": "We have used analysis of ethidium-bromide-stained reverse transcriptase-polymerase chain reaction (RT-PCR) products to assess the effects of X-chromosome inactivation during spermatogenesis in the mouse. RT-PCR was performed on total RNA from eight different spermatogenic cell types, including premeiotic spermatogonia, meiotic spermatocytes, and postmeiotic spermatids, to detect transcripts from five different X-linked structural genes (Pgk-1, Zfx, Pdha-1, Hprt, and Phka) and two autosomal genes (Pgk-2 and beta-actin). Relative intensities of ethidium-bromide-stained RT-PCR products representing transcripts from each gene in each cell type were analyzed by densitometry using the Image program (version 1.4, NIH), and normalized against beta-actin values. These results suggest a coordinate inactivation of the X-linked loci at the onset of meiosis, followed by variable rates of decline of corresponding transcript levels reflecting differential mRNA stabilities and/or leaky expression after inactivation. Technically, these results indicate that analysis of ethidium-bromide-stained RT-PCR products can be used to provide a \"semiquantitative\" indication of relative levels of specific transcripts in a developing cell lineage without using radioactive probes to quantitate these products.", "contents": "Semiquantitative analysis of X-linked gene expression during spermatogenesis in the mouse: ethidium-bromide staining of RT-PCR products. We have used analysis of ethidium-bromide-stained reverse transcriptase-polymerase chain reaction (RT-PCR) products to assess the effects of X-chromosome inactivation during spermatogenesis in the mouse. RT-PCR was performed on total RNA from eight different spermatogenic cell types, including premeiotic spermatogonia, meiotic spermatocytes, and postmeiotic spermatids, to detect transcripts from five different X-linked structural genes (Pgk-1, Zfx, Pdha-1, Hprt, and Phka) and two autosomal genes (Pgk-2 and beta-actin). Relative intensities of ethidium-bromide-stained RT-PCR products representing transcripts from each gene in each cell type were analyzed by densitometry using the Image program (version 1.4, NIH), and normalized against beta-actin values. These results suggest a coordinate inactivation of the X-linked loci at the onset of meiosis, followed by variable rates of decline of corresponding transcript levels reflecting differential mRNA stabilities and/or leaky expression after inactivation. Technically, these results indicate that analysis of ethidium-bromide-stained RT-PCR products can be used to provide a \"semiquantitative\" indication of relative levels of specific transcripts in a developing cell lineage without using radioactive probes to quantitate these products."} {"id": "PMID:1282027", "title": "Preoperative medical evaluation of the vascular patient.", "content": "The vascular patient has a systemic disease, atherosclerosis, and this may be present in all arteries in varying degrees. Thus, preoperative evaluation of the vascular patient is essential to identify areas of risk. The cardiovascular system is the chief source of mortality and morbidity. Primary emphasis will be placed on the diagnostic tests involved and the nursing responsibility to the patient.", "contents": "Preoperative medical evaluation of the vascular patient. The vascular patient has a systemic disease, atherosclerosis, and this may be present in all arteries in varying degrees. Thus, preoperative evaluation of the vascular patient is essential to identify areas of risk. The cardiovascular system is the chief source of mortality and morbidity. Primary emphasis will be placed on the diagnostic tests involved and the nursing responsibility to the patient."} {"id": "PMID:1282028", "title": "Atherosclerotic occlusive disease of the aorta.", "content": "Aortoiliac occlusive disease is a common manifestation of atherosclerosis. Signs and symptoms include intermittent claudication, diminished femoral pulses, and impotence in males. During the assessment process, the coronary, renal, cerebrovascular, and distal extremity vessels must also be evaluated. Treatment options include conservative measures including angioplasty, as well as surgical intervention including aortic reconstruction or extra-anatomic bypass surgery.", "contents": "Atherosclerotic occlusive disease of the aorta. Aortoiliac occlusive disease is a common manifestation of atherosclerosis. Signs and symptoms include intermittent claudication, diminished femoral pulses, and impotence in males. During the assessment process, the coronary, renal, cerebrovascular, and distal extremity vessels must also be evaluated. Treatment options include conservative measures including angioplasty, as well as surgical intervention including aortic reconstruction or extra-anatomic bypass surgery."} {"id": "PMID:1282029", "title": "Differing epitope selection of experimentally-induced and natural antibodies to a disease-specific autoantigen, the E2 subunit of pyruvate dehydrogenase complex (PDC-E2).", "content": "Naturally-occurring autoantibodies to a family of mitochondrial enzymes, the 2-oxoacid dehydrogenase complexes (2-OADC), characterize the human liver disease primary biliary cirrhosis. The immunodominant epitope for these autoantibodies is associated with the lipoyl-binding domain of the E2 subunit of the enzymes. The reactivity of these disease-associated autoantibodies was compared with that of antibodies raised in rats and rabbits, by immunization with various preparations derived from the 2-OADC enzymes, using immunization protocols that have successfully induced various organ-specific autoimmune diseases in animals. The immunogens included the intact pyruvate dehydrogenase complex (PDC) from bovine heart, human recombinant PDC-E2, and short synthetic peptides representing the immunodominant lipoic acid binding sequences of the 2-OADC enzymes. The techniques for antibody analysis included immunofluorescence, immunoblotting on mitochondrial extracts, ELISAs using entire PDC, PDC-E2, or synthetic peptides, epitope mapping by peptide scanning on overlapping octameric peptides representing the human PDC-E2 sequence, affinity purification on PDC-E2, and inhibition in vitro by sera of the catalytic function of PDC. Experimental immunization did not elicit any evidence of autoimmune disease. Moreover, the experimentally-induced antibodies in striking contrast to the natural autoantibodies showed preferential reactivity with PDC-E2 rather than with intact PDC, failed to inhibit in vitro the catalytic function of PDC, and, on peptide scanning, reacted with discrete epitopes, but at sites other than the lipoyl-binding region of PDC-E2. Our data indicate that 'multisystem' autoimmune diseases including primary biliary cirrhosis may not be elicitable experimentally because a critical disease-relevant autoepitope is not engaged by the immune system.", "contents": "Differing epitope selection of experimentally-induced and natural antibodies to a disease-specific autoantigen, the E2 subunit of pyruvate dehydrogenase complex (PDC-E2). Naturally-occurring autoantibodies to a family of mitochondrial enzymes, the 2-oxoacid dehydrogenase complexes (2-OADC), characterize the human liver disease primary biliary cirrhosis. The immunodominant epitope for these autoantibodies is associated with the lipoyl-binding domain of the E2 subunit of the enzymes. The reactivity of these disease-associated autoantibodies was compared with that of antibodies raised in rats and rabbits, by immunization with various preparations derived from the 2-OADC enzymes, using immunization protocols that have successfully induced various organ-specific autoimmune diseases in animals. The immunogens included the intact pyruvate dehydrogenase complex (PDC) from bovine heart, human recombinant PDC-E2, and short synthetic peptides representing the immunodominant lipoic acid binding sequences of the 2-OADC enzymes. The techniques for antibody analysis included immunofluorescence, immunoblotting on mitochondrial extracts, ELISAs using entire PDC, PDC-E2, or synthetic peptides, epitope mapping by peptide scanning on overlapping octameric peptides representing the human PDC-E2 sequence, affinity purification on PDC-E2, and inhibition in vitro by sera of the catalytic function of PDC. Experimental immunization did not elicit any evidence of autoimmune disease. Moreover, the experimentally-induced antibodies in striking contrast to the natural autoantibodies showed preferential reactivity with PDC-E2 rather than with intact PDC, failed to inhibit in vitro the catalytic function of PDC, and, on peptide scanning, reacted with discrete epitopes, but at sites other than the lipoyl-binding region of PDC-E2. Our data indicate that 'multisystem' autoimmune diseases including primary biliary cirrhosis may not be elicitable experimentally because a critical disease-relevant autoepitope is not engaged by the immune system."} {"id": "PMID:1282030", "title": "Deficient surface expression of glycosylphosphatidylinositol-anchored proteins in B cell lines established from patients with paroxysmal nocturnal hemoglobinuria.", "content": "Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired type hemolytic disorder. Hematopoietic cells of patients with PNH are deficient in glycosylphosphatidylinositol (GPI) anchored membrane proteins. Since some membrane-bound complement inhibitors, such as CD59 and decay accelerating factor (DAF), are GPI anchored proteins, abnormal cells from patients with PNH are sensitive to complement attack. Their myeloid and erythroid cells are affected more than their lymphoid cells. Patients whose B cells were severely deficient in GPI anchored proteins were chosen to establish cell lines by Epstein-Barr virus mediated transformation. The lines established (SS-1-, TK-1-, and TK-14- cell lines) had the following characteristics of PNH. First, GPI anchored proteins were completely absent from the surface of SS-1- and TK-14- cells, and were expressed at very low levels on TK-1- cells, whereas polypeptide anchored proteins were normally expressed on these three lines. Secondly, DAF mRNAs of the SS-1- cell line were qualitatively and quantitatively indistinguishable from those of a control, wild-type cell line. Third, pro-CD59 and pro-DAF molecules were detected intracellularly in these cell lines, their pro-CD59 being smaller and more hydrophilic than that from a wild-type cell line. These cell lines should be useful in further studies on the pathogenesis of PNH.", "contents": "Deficient surface expression of glycosylphosphatidylinositol-anchored proteins in B cell lines established from patients with paroxysmal nocturnal hemoglobinuria. Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired type hemolytic disorder. Hematopoietic cells of patients with PNH are deficient in glycosylphosphatidylinositol (GPI) anchored membrane proteins. Since some membrane-bound complement inhibitors, such as CD59 and decay accelerating factor (DAF), are GPI anchored proteins, abnormal cells from patients with PNH are sensitive to complement attack. Their myeloid and erythroid cells are affected more than their lymphoid cells. Patients whose B cells were severely deficient in GPI anchored proteins were chosen to establish cell lines by Epstein-Barr virus mediated transformation. The lines established (SS-1-, TK-1-, and TK-14- cell lines) had the following characteristics of PNH. First, GPI anchored proteins were completely absent from the surface of SS-1- and TK-14- cells, and were expressed at very low levels on TK-1- cells, whereas polypeptide anchored proteins were normally expressed on these three lines. Secondly, DAF mRNAs of the SS-1- cell line were qualitatively and quantitatively indistinguishable from those of a control, wild-type cell line. Third, pro-CD59 and pro-DAF molecules were detected intracellularly in these cell lines, their pro-CD59 being smaller and more hydrophilic than that from a wild-type cell line. These cell lines should be useful in further studies on the pathogenesis of PNH."} {"id": "PMID:1282031", "title": "Immune escape by Epstein-Barr virus (EBV) carrying Burkitt's lymphoma: in vitro reconstitution of sensitivity to EBV-specific cytotoxic T cells.", "content": "Epstein-Barr virus (EBV) positive Burkitt's lymphoma (BL) cells are markedly less sensitive to EBV-specific cytotoxic T cell (CTL) recognition than EBV-transformed lymphoblastoid cell lines of normal B cell origin. Three features of the BL cell phenotype might contribute to this reduced susceptibility: (i) low expression of cell adhesion molecules, (ii) low expression of HLA class I and selective down-regulation of particular alleles, and (iii) down-regulation of all transformation-associated EBV antigens except EBV-encoded nuclear antigen (EBNA)-1. This study assesses the individual importance of each of these features for immune escape. For this purpose the WW1-BL cell line was used which expresses all the known transformation-associated EBV antigens (EBNA-1 to -6 and latent membrane protein-1 and -2) but which is negative for HLA A11 and for the adhesion molecule leukocyte function associated antigen-3 (LFA-3). Using recombinant vectors, these deficiencies have been sequentially corrected and the cells have been tested for sensitivity to EBV (B95.8 strain)-induced CTL preparations recognizing epitope(s) of EBNA-4 in the context of HLA A11. Expression of HLA A11 alone or in combination with LFA-3 did not sensitize WW1-BL cells to these effectors. Lysis was only achieved when HLA A11 was co-expressed with the B95.8 virus-encoded EBNA-4 protein, and in these circumstances sensitization did not require LFA-3. These results indicate that reconstitution of the relevant HLA-EBV epitope target complex on the cell membrane is sufficient to render BL cells sensitive to virus-specific cytolysis. The requirement for EBNA-4 reconstitution to achieve lysis of the WW1-BL/A11 transfectant suggested that the resident WW1 virus-encoded EBNA-4 protein did not contain the relevant target epitope for HLA A11-restricted recognition. This was confirmed by transferring the WW1 virus isolate into another A11-positive B cell background.", "contents": "Immune escape by Epstein-Barr virus (EBV) carrying Burkitt's lymphoma: in vitro reconstitution of sensitivity to EBV-specific cytotoxic T cells. Epstein-Barr virus (EBV) positive Burkitt's lymphoma (BL) cells are markedly less sensitive to EBV-specific cytotoxic T cell (CTL) recognition than EBV-transformed lymphoblastoid cell lines of normal B cell origin. Three features of the BL cell phenotype might contribute to this reduced susceptibility: (i) low expression of cell adhesion molecules, (ii) low expression of HLA class I and selective down-regulation of particular alleles, and (iii) down-regulation of all transformation-associated EBV antigens except EBV-encoded nuclear antigen (EBNA)-1. This study assesses the individual importance of each of these features for immune escape. For this purpose the WW1-BL cell line was used which expresses all the known transformation-associated EBV antigens (EBNA-1 to -6 and latent membrane protein-1 and -2) but which is negative for HLA A11 and for the adhesion molecule leukocyte function associated antigen-3 (LFA-3). Using recombinant vectors, these deficiencies have been sequentially corrected and the cells have been tested for sensitivity to EBV (B95.8 strain)-induced CTL preparations recognizing epitope(s) of EBNA-4 in the context of HLA A11. Expression of HLA A11 alone or in combination with LFA-3 did not sensitize WW1-BL cells to these effectors. Lysis was only achieved when HLA A11 was co-expressed with the B95.8 virus-encoded EBNA-4 protein, and in these circumstances sensitization did not require LFA-3. These results indicate that reconstitution of the relevant HLA-EBV epitope target complex on the cell membrane is sufficient to render BL cells sensitive to virus-specific cytolysis. The requirement for EBNA-4 reconstitution to achieve lysis of the WW1-BL/A11 transfectant suggested that the resident WW1 virus-encoded EBNA-4 protein did not contain the relevant target epitope for HLA A11-restricted recognition. This was confirmed by transferring the WW1 virus isolate into another A11-positive B cell background."} {"id": "PMID:1282032", "title": "Memory T cells of a patient with follicular thyroid carcinoma recognize peptides derived from mutated p21 ras (Gln-->Leu61).", "content": "Point mutations in ras genes resulting in substitutions of amino acid Gly in positions 12 and 13, and Gln in position 61 of the ras gene product p21, are commonly found in human tumors. Peptides derived from aberrant p21 may elicit a tumor specific T cell response, provided that these peptides can bind to HLA molecules of the tumor and the patient has T cells able to recognize the corresponding peptide-HLA complex. Here we report that CD4+ T cells of memory type (CD45RO+) from a patient with a follicular thyroid carcinoma respond against a synthetic peptide derived from aberrant p21 ras having a Gln-->Leu substitution at position 61. Such responses were not observed when T cells from healthy volunteers or cancer patients where this mutation does not usually occur were stimulated with this peptide. The responding T cells did not cross-react with the corresponding peptide derived from native p21 ras nor did they recognize peptides carrying other substitutions in position 61. T cells clones were generated which recognized this Leu61 peptide when presented by HLA-DQ8 molecules. These T cell clones also recognized the corresponding intact p21 ras protein. By using several different synthetic peptides, a peptide with optimal stimulatory capacity was defined. Performing polymerase chain reaction and oligonucleotide probing we were, however, not able to detect the p21 ras gene encoding the Gln-->Leu substitution in DNA from tumor biopsies from the patient. This may indicate that tumor cells harboring the mutation leading to the Gln-->Leu substitution had been eliminated and that tumor progression was due to cells that had deleted the mutated ras gene. The finding that ras derived peptides and recombinant mutated p21 ras are immunogenic in man may form the basis for the development of cancer immunotherapy based on synthetic oncogene derived peptides.", "contents": "Memory T cells of a patient with follicular thyroid carcinoma recognize peptides derived from mutated p21 ras (Gln-->Leu61). Point mutations in ras genes resulting in substitutions of amino acid Gly in positions 12 and 13, and Gln in position 61 of the ras gene product p21, are commonly found in human tumors. Peptides derived from aberrant p21 may elicit a tumor specific T cell response, provided that these peptides can bind to HLA molecules of the tumor and the patient has T cells able to recognize the corresponding peptide-HLA complex. Here we report that CD4+ T cells of memory type (CD45RO+) from a patient with a follicular thyroid carcinoma respond against a synthetic peptide derived from aberrant p21 ras having a Gln-->Leu substitution at position 61. Such responses were not observed when T cells from healthy volunteers or cancer patients where this mutation does not usually occur were stimulated with this peptide. The responding T cells did not cross-react with the corresponding peptide derived from native p21 ras nor did they recognize peptides carrying other substitutions in position 61. T cells clones were generated which recognized this Leu61 peptide when presented by HLA-DQ8 molecules. These T cell clones also recognized the corresponding intact p21 ras protein. By using several different synthetic peptides, a peptide with optimal stimulatory capacity was defined. Performing polymerase chain reaction and oligonucleotide probing we were, however, not able to detect the p21 ras gene encoding the Gln-->Leu substitution in DNA from tumor biopsies from the patient. This may indicate that tumor cells harboring the mutation leading to the Gln-->Leu substitution had been eliminated and that tumor progression was due to cells that had deleted the mutated ras gene. The finding that ras derived peptides and recombinant mutated p21 ras are immunogenic in man may form the basis for the development of cancer immunotherapy based on synthetic oncogene derived peptides."} {"id": "PMID:1282033", "title": "Evidence for RNA in the peptidyl transferase center of Escherichia coli ribosomes as indicated by fluorescence.", "content": "A coumarin derivative was covalently attached to either the amino acid or the 5' end of phenylalanine-specific transfer RNA (tRNA(phe)). Its fluorescence was quenched by methyl viologen when the tRNA was free in solution or bound to Escherichia coli ribosomes. Methyl viologen as a cation in solution has a strong affinity for the ionized phosphates of a nucleic acid and so can be used to qualitatively measure the presence of RNA in the immediate vicinity of the tRNA-linked coumarins upon binding to ribosomes. Fluorescence lifetime measurements indicate that the increase in fluorescence quenching observed when the tRNAs are bound into the peptidyl site of ribosomes is due to static quenching by methyl viologen bound to RNA in the immediate vicinity of the fluorophore. The data lead to the conclusion that the ribosome peptidyl transferase center is rich in ribosomal RNA. Movement of the fluorophore at the N-terminus of the nascent peptide as it is extended or movement of the tRNA acceptor stem away from the peptidyl transferase center during peptide bond formation appears to result in movement of the probe into a region containing less rRNA.", "contents": "Evidence for RNA in the peptidyl transferase center of Escherichia coli ribosomes as indicated by fluorescence. A coumarin derivative was covalently attached to either the amino acid or the 5' end of phenylalanine-specific transfer RNA (tRNA(phe)). Its fluorescence was quenched by methyl viologen when the tRNA was free in solution or bound to Escherichia coli ribosomes. Methyl viologen as a cation in solution has a strong affinity for the ionized phosphates of a nucleic acid and so can be used to qualitatively measure the presence of RNA in the immediate vicinity of the tRNA-linked coumarins upon binding to ribosomes. Fluorescence lifetime measurements indicate that the increase in fluorescence quenching observed when the tRNAs are bound into the peptidyl site of ribosomes is due to static quenching by methyl viologen bound to RNA in the immediate vicinity of the fluorophore. The data lead to the conclusion that the ribosome peptidyl transferase center is rich in ribosomal RNA. Movement of the fluorophore at the N-terminus of the nascent peptide as it is extended or movement of the tRNA acceptor stem away from the peptidyl transferase center during peptide bond formation appears to result in movement of the probe into a region containing less rRNA."} {"id": "PMID:1282034", "title": "Nonresectable esophageal cancer.", "content": "Esophageal cancer is a devastating illness that has often metastasized before diagnosis. Diagnostic options include barium x-ray and endoscopy. Staging is most accurate using endoscopic ultrasonography. Treatment modalities that are widely used include radiotherapy, chemotherapy, dilatation, prosthesis placement, neodymium-yttrium-aluminum-garnet laser and combinations thereof. Photodynamic therapy is a treatment currently used on an experimental basis that offers selective ablation of cancerous cells. Nursing support for these patients is critically important and must be ongoing. Education for patients and families is continuous throughout the course of treatment.", "contents": "Nonresectable esophageal cancer. Esophageal cancer is a devastating illness that has often metastasized before diagnosis. Diagnostic options include barium x-ray and endoscopy. Staging is most accurate using endoscopic ultrasonography. Treatment modalities that are widely used include radiotherapy, chemotherapy, dilatation, prosthesis placement, neodymium-yttrium-aluminum-garnet laser and combinations thereof. Photodynamic therapy is a treatment currently used on an experimental basis that offers selective ablation of cancerous cells. Nursing support for these patients is critically important and must be ongoing. Education for patients and families is continuous throughout the course of treatment."} {"id": "PMID:1282035", "title": "Use of dextran 70 to estimate peritoneal lymphatic absorption rate in CAPD.", "content": "Peritoneal lymphatic absorption rate (LAR) in 15 patients on a CAPD program was measured by estimation of the disappearance of dextran 70 from the peritoneal cavity. The LAR was 1.03 +/- 0.45 ml/min. The cumulative lymphatic absorption, cumulative net transcapillary ultrafiltration, calculated net ultrafiltration (CUF) and measured net ultrafiltration (MUF) at 4 h exchange were respectively: 261 +/- 127 ml, 694 +/- 134 ml, 446 +/- 135 ml and 409 +/- 136 ml. Calculated and measured net ultrafiltration didn't differ significantly. An inverse correlation between MUF and LAR and a positive correlation between MUF and the ratio for dialysate glucose concentration at 4 hand dialysate glucose at 0 h (G4/G0) were observed (r = -0.522 and 0.547, respectively, p < 0.05). The multiple correlation coefficient between the MUF and LAR plus G4/G0 was higher (r = 0.617, p < 0.05). Peritonitis and the presence of diabetes didn't interfere with LAR. We have concluded that lymphatic absorption plus peritoneal transfer rate of glucose are important determinants of intraperitoneal volumes and that dextran 70 is a useful marker to measure lymphatic absorption.", "contents": "Use of dextran 70 to estimate peritoneal lymphatic absorption rate in CAPD. Peritoneal lymphatic absorption rate (LAR) in 15 patients on a CAPD program was measured by estimation of the disappearance of dextran 70 from the peritoneal cavity. The LAR was 1.03 +/- 0.45 ml/min. The cumulative lymphatic absorption, cumulative net transcapillary ultrafiltration, calculated net ultrafiltration (CUF) and measured net ultrafiltration (MUF) at 4 h exchange were respectively: 261 +/- 127 ml, 694 +/- 134 ml, 446 +/- 135 ml and 409 +/- 136 ml. Calculated and measured net ultrafiltration didn't differ significantly. An inverse correlation between MUF and LAR and a positive correlation between MUF and the ratio for dialysate glucose concentration at 4 hand dialysate glucose at 0 h (G4/G0) were observed (r = -0.522 and 0.547, respectively, p < 0.05). The multiple correlation coefficient between the MUF and LAR plus G4/G0 was higher (r = 0.617, p < 0.05). Peritonitis and the presence of diabetes didn't interfere with LAR. We have concluded that lymphatic absorption plus peritoneal transfer rate of glucose are important determinants of intraperitoneal volumes and that dextran 70 is a useful marker to measure lymphatic absorption."} {"id": "PMID:1282036", "title": "Residual volume measurements in CAPD patients with exogenous and endogenous solutes.", "content": "Accurate residual volume (RV) measurements are needed in studies on fluid kinetics during CAPD. In this study 10 stable CAPD patients were examined twice within 1 week. On both occasions RV after drainage was calculated by the indicator dilution method. Exogenous (dextran 70, inulin) and endogenous (albumin, IgG, urea, creatinine) solutes were used as markers. RV calculated with endogenous solutes (mean +/- SD) were significantly higher than those calculated with dextran (232 +/- 77 mL) and inulin (223 +/- 73): albumin (389 +/- 123), IgG (497 +/- 180), urea (465 +/- 129) and creatinine (429 +/- 109). The relationship between RV calculated with exogenous solutes was much better than between those calculated with endogenous solutes: dextran vs inulin (r = 0.91), albumin vs IgG (r = 0.69) and urea vs creatinine (r = 0.63). Since mass transport of endogenous solutes during rinsing time exceeds mass transport of dextran and inulin, RV was also calculated after corrections had been made for diffusive mass transport of endogenous solutes during the rinsing procedure. After this correction only albumin was similar to exogenous solutes (244 +/- 111 mL) and had an acceptable confidence interval when compared to dextran. No correlation was found between RV on the first and second day, suggesting large intra-individual variability. We conclude that RV should be calculated with dextran or inulin. When no exogenous solutes are used, albumin is the best alternative. However, only rough estimations are obtained when no correction for diffusion is applied.", "contents": "Residual volume measurements in CAPD patients with exogenous and endogenous solutes. Accurate residual volume (RV) measurements are needed in studies on fluid kinetics during CAPD. In this study 10 stable CAPD patients were examined twice within 1 week. On both occasions RV after drainage was calculated by the indicator dilution method. Exogenous (dextran 70, inulin) and endogenous (albumin, IgG, urea, creatinine) solutes were used as markers. RV calculated with endogenous solutes (mean +/- SD) were significantly higher than those calculated with dextran (232 +/- 77 mL) and inulin (223 +/- 73): albumin (389 +/- 123), IgG (497 +/- 180), urea (465 +/- 129) and creatinine (429 +/- 109). The relationship between RV calculated with exogenous solutes was much better than between those calculated with endogenous solutes: dextran vs inulin (r = 0.91), albumin vs IgG (r = 0.69) and urea vs creatinine (r = 0.63). Since mass transport of endogenous solutes during rinsing time exceeds mass transport of dextran and inulin, RV was also calculated after corrections had been made for diffusive mass transport of endogenous solutes during the rinsing procedure. After this correction only albumin was similar to exogenous solutes (244 +/- 111 mL) and had an acceptable confidence interval when compared to dextran. No correlation was found between RV on the first and second day, suggesting large intra-individual variability. We conclude that RV should be calculated with dextran or inulin. When no exogenous solutes are used, albumin is the best alternative. However, only rough estimations are obtained when no correction for diffusion is applied."} {"id": "PMID:1282037", "title": "Evidence of a physiological role for bombesin in the postnatal development of the rabbit pancreas.", "content": "The effect of chronic administration of bombesin (BBN) on the development of the pancreas and the role of endogenous BBN in the postnatal development of exocrine pancreatic function were investigated in suckling New Zealand White rabbits. BBN administered intraperitoneally (i.p) at various doses (1.25, 12.5 and 30 micrograms/kg body weight) to suckling rabbits for 13 days starting on day 4 of life induced pancreatic growth as characterized by dose-dependent increases in pancreatic wet weight, total protein content and total DNA content compared to littermate controls. The maximum effect was observed using bombesin at 30 micrograms/kg. This increase represented hyperplasia since there was no BBN-induced change in the protein:DNA ratio. Pancreatic amylase activity was significantly increased by all doses of BBN, with a maximal effect at 1.25 micrograms/kg. The specific BBN receptor antagonist [Leu13-psi(CH2NH)Leu14]-BBN, given i.p for 9 days at 30 micrograms/kg body weight starting on day 20 of life, significantly reduced the development of pancreatic amylase and lipase activities compared to controls (48 and 36% reductions, respectively). Our findings confirm the trophic effect of BBN on the neonatal pancreas and provide evidence of a physiological role for endogenous BBN-peptides in the development of pancreatic exocrine function.", "contents": "Evidence of a physiological role for bombesin in the postnatal development of the rabbit pancreas. The effect of chronic administration of bombesin (BBN) on the development of the pancreas and the role of endogenous BBN in the postnatal development of exocrine pancreatic function were investigated in suckling New Zealand White rabbits. BBN administered intraperitoneally (i.p) at various doses (1.25, 12.5 and 30 micrograms/kg body weight) to suckling rabbits for 13 days starting on day 4 of life induced pancreatic growth as characterized by dose-dependent increases in pancreatic wet weight, total protein content and total DNA content compared to littermate controls. The maximum effect was observed using bombesin at 30 micrograms/kg. This increase represented hyperplasia since there was no BBN-induced change in the protein:DNA ratio. Pancreatic amylase activity was significantly increased by all doses of BBN, with a maximal effect at 1.25 micrograms/kg. The specific BBN receptor antagonist [Leu13-psi(CH2NH)Leu14]-BBN, given i.p for 9 days at 30 micrograms/kg body weight starting on day 20 of life, significantly reduced the development of pancreatic amylase and lipase activities compared to controls (48 and 36% reductions, respectively). Our findings confirm the trophic effect of BBN on the neonatal pancreas and provide evidence of a physiological role for endogenous BBN-peptides in the development of pancreatic exocrine function."} {"id": "PMID:1282038", "title": "Stimulatory effect of pigeon milk growth factor on protein and nucleic acid synthesis in neonate mice.", "content": "Effect of subcutaneously administered pigeon milk-derived growth factor (PMGF) on protein and nucleic acid content of various body organs was studied in neonate mice. Although the body and organ weights of PMGF-treated mice did not differ from those of controls, the weight of testes was significantly higher in the former than the latter. The treated animals had significantly greater content of protein (in liver and skin), DNA (in liver, lung, stomach, duodenum, ileum and rectum) and RNA (in liver, stomach, ileum and skin). The protein/DNA ratio was lower in many organs of PMGF-treated mice. These results indicate that the biological properties of PMGF bear semblance to those of epidermal growth factor isolated from mouse salivary gland and human milk.", "contents": "Stimulatory effect of pigeon milk growth factor on protein and nucleic acid synthesis in neonate mice. Effect of subcutaneously administered pigeon milk-derived growth factor (PMGF) on protein and nucleic acid content of various body organs was studied in neonate mice. Although the body and organ weights of PMGF-treated mice did not differ from those of controls, the weight of testes was significantly higher in the former than the latter. The treated animals had significantly greater content of protein (in liver and skin), DNA (in liver, lung, stomach, duodenum, ileum and rectum) and RNA (in liver, stomach, ileum and skin). The protein/DNA ratio was lower in many organs of PMGF-treated mice. These results indicate that the biological properties of PMGF bear semblance to those of epidermal growth factor isolated from mouse salivary gland and human milk."} {"id": "PMID:1282039", "title": "Relationship between autoepitope and DNA-binding site on a histone H1 molecule.", "content": "Autoepitope and DNA-binding domain on a histone H1 molecule were compared using truncated histone H1 peptides as antigens. At least two epitopes (epitope A, N-terminal side; epitope B, C-terminal side) were found both of which were composed of approximately 20 amino acids. IgM from all 17 anti-histone H1-positive SLE sera reacted with epitope A. IgG from 12 sera reacted with epitope A and IgG from 4 sera reacted with epitope B. In one case, no IgG anti-histone H1 reactivities were found while IgM from the same patient reacted with epitope A. Epitope A had the ability to bind DNA. The reactivities against histone H1 of affinity-purified antiepitope A autoantibodies were inhibited by DNA. These data suggest that some anti-histone H1 antibodies are directed against a histone H1 DNA-binding site, raising the possibility that an idiotype/anti-idiotype network, at least in part, is involved in the generation of anti-histone H1 autoantibodies.", "contents": "Relationship between autoepitope and DNA-binding site on a histone H1 molecule. Autoepitope and DNA-binding domain on a histone H1 molecule were compared using truncated histone H1 peptides as antigens. At least two epitopes (epitope A, N-terminal side; epitope B, C-terminal side) were found both of which were composed of approximately 20 amino acids. IgM from all 17 anti-histone H1-positive SLE sera reacted with epitope A. IgG from 12 sera reacted with epitope A and IgG from 4 sera reacted with epitope B. In one case, no IgG anti-histone H1 reactivities were found while IgM from the same patient reacted with epitope A. Epitope A had the ability to bind DNA. The reactivities against histone H1 of affinity-purified antiepitope A autoantibodies were inhibited by DNA. These data suggest that some anti-histone H1 antibodies are directed against a histone H1 DNA-binding site, raising the possibility that an idiotype/anti-idiotype network, at least in part, is involved in the generation of anti-histone H1 autoantibodies."} {"id": "PMID:1282040", "title": "Model building of DNA/RNA triple helix containing L-deoxyadenosine.", "content": "A three-dimensional model of DNA/RNA triple helix that contains a poly(L-deoxyadenosine) (L-dA) chain is proposed based on computer-assisted model building and energy calculations. The model building was performed by a new method that systematically searches possible conformations of nucleotide units in the helical chains. Two possible orientations of sugar-phosphate chains, in which two homopyrimidine strands are parallel or antiparallel with each other, were considered in the systematic search. Several possible base-pairing models, in which there are one Watson-Crick base pair and one other base pair, were also considered. Many possible models selected by the systematic search were further refined through molecular mechanics calculation incorporating a helical boundary condition. The preferred model, which was selected on the basis of potential energy, was the one with Watson-Crick and Hoogsteen base pairs and with its two polypyrimidine chains in the antiparallel orientation. The model can explain the experimental observation that poly(L-dA) forms a stable triple helix with poly(uridylic acid) (U) but not with poly(deoxythymidylic acid) (dT).", "contents": "Model building of DNA/RNA triple helix containing L-deoxyadenosine. A three-dimensional model of DNA/RNA triple helix that contains a poly(L-deoxyadenosine) (L-dA) chain is proposed based on computer-assisted model building and energy calculations. The model building was performed by a new method that systematically searches possible conformations of nucleotide units in the helical chains. Two possible orientations of sugar-phosphate chains, in which two homopyrimidine strands are parallel or antiparallel with each other, were considered in the systematic search. Several possible base-pairing models, in which there are one Watson-Crick base pair and one other base pair, were also considered. Many possible models selected by the systematic search were further refined through molecular mechanics calculation incorporating a helical boundary condition. The preferred model, which was selected on the basis of potential energy, was the one with Watson-Crick and Hoogsteen base pairs and with its two polypyrimidine chains in the antiparallel orientation. The model can explain the experimental observation that poly(L-dA) forms a stable triple helix with poly(uridylic acid) (U) but not with poly(deoxythymidylic acid) (dT)."} {"id": "PMID:1282041", "title": "Interaction of substance P and its N- and C-terminal fragments with Ca2+: implications for hormone action.", "content": "In an attempt to understand the role of Ca2+ on the bioactive conformation of peptide hormones, we have examined the interaction between Ca2+ and the neuropeptide substance P. Using CD spectroscopy to monitor conformational changes caused by Ca2+ binding, we found no significant binding of the cation by substance P in water. However, a substantial conformational change occurred in the hormone on Ca2+ addition in trifluoroethanol or an 80:20 (v/v) mixture of acetonitrile and trifluoroethanol. A biphasic binding of Ca2+ was observed in these solvents with saturation at 2 cations per hormone molecule. Mg2+ caused a relatively smaller conformational change in the hormone. A peptide corresponding to residues 1-7 at the N-terminal fragment of substance P showed a weak nonsaturating binding of Ca2+ in the nonpolar solvents whereas the 7-11 C-terminal fragment peptide displayed a binding indicative of an 1:1 Ca2+/peptide complex. Ca2+ binding by the hormone and the 7-11 fragment was also monitored by changes in fluorescence of the phenylalanyl residues. The results support the conclusion drawn from the CD data about a distinct Ca2+ binding site in the C-terminal part of substance P. The Kd values obtained from fluorescence data were 160 microM for Ca2+ and 1 mM for Mg2+ binding by substance P. The hormone and the two peptide fragments were also tested for their effect on the stability of dimyristoyl lecithin vesicles. Substance P and the N-terminal fragment caused no significant leakage of either fluorescent dyes or K+ trapped in the vesicles. Nor did they cause membrane fusion as monitored by the fluorescence quenching method.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Interaction of substance P and its N- and C-terminal fragments with Ca2+: implications for hormone action. In an attempt to understand the role of Ca2+ on the bioactive conformation of peptide hormones, we have examined the interaction between Ca2+ and the neuropeptide substance P. Using CD spectroscopy to monitor conformational changes caused by Ca2+ binding, we found no significant binding of the cation by substance P in water. However, a substantial conformational change occurred in the hormone on Ca2+ addition in trifluoroethanol or an 80:20 (v/v) mixture of acetonitrile and trifluoroethanol. A biphasic binding of Ca2+ was observed in these solvents with saturation at 2 cations per hormone molecule. Mg2+ caused a relatively smaller conformational change in the hormone. A peptide corresponding to residues 1-7 at the N-terminal fragment of substance P showed a weak nonsaturating binding of Ca2+ in the nonpolar solvents whereas the 7-11 C-terminal fragment peptide displayed a binding indicative of an 1:1 Ca2+/peptide complex. Ca2+ binding by the hormone and the 7-11 fragment was also monitored by changes in fluorescence of the phenylalanyl residues. The results support the conclusion drawn from the CD data about a distinct Ca2+ binding site in the C-terminal part of substance P. The Kd values obtained from fluorescence data were 160 microM for Ca2+ and 1 mM for Mg2+ binding by substance P. The hormone and the two peptide fragments were also tested for their effect on the stability of dimyristoyl lecithin vesicles. Substance P and the N-terminal fragment caused no significant leakage of either fluorescent dyes or K+ trapped in the vesicles. Nor did they cause membrane fusion as monitored by the fluorescence quenching method.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282042", "title": "Postoperative changes in coagulant and anticoagulant factors following abdominal aortic surgery.", "content": "The extent and time course of changes in selected procoagulant and anticoagulant factors were investigated in 19 patients undergoing elective abdominal aortic surgery. The coagulation factors were measured preoperatively, and on days two, four, and six postoperatively. It was found that there were no significant changes outside the normal range in prothrombin time, partial thromboplastin time, or thrombin clotting time. However, there were large increases in the procoagulants, fibrinogen, factor VIII coagulant, factor VIIIRag/von Willebrand factor, and in alpha 1-antitrypsin. Over the same time there were marked decreases in the naturally occurring anticoagulants, protein C and antithrombin III, and in alpha 2-macroglobulin. These changes implied that the patients were \"hypercoagulable\" in the postoperative period. The maximum changes in the procoagulants occurred on either postoperative day two or day four. The maximum changes in the natural anticoagulants occurred on postoperative day two. There were no significant changes in factor V, factor X, alpha 2-antiplasmin, or platelet aggregability. The timing of the changes coincided with a period of high risk of perioperative myocardial infarction in this group of patients. Thus, it is possible that postoperative hypercoagulability contributes to the development of coronary artery thrombosis and myocardial infarction following abdominal aortic surgery.", "contents": "Postoperative changes in coagulant and anticoagulant factors following abdominal aortic surgery. The extent and time course of changes in selected procoagulant and anticoagulant factors were investigated in 19 patients undergoing elective abdominal aortic surgery. The coagulation factors were measured preoperatively, and on days two, four, and six postoperatively. It was found that there were no significant changes outside the normal range in prothrombin time, partial thromboplastin time, or thrombin clotting time. However, there were large increases in the procoagulants, fibrinogen, factor VIII coagulant, factor VIIIRag/von Willebrand factor, and in alpha 1-antitrypsin. Over the same time there were marked decreases in the naturally occurring anticoagulants, protein C and antithrombin III, and in alpha 2-macroglobulin. These changes implied that the patients were \"hypercoagulable\" in the postoperative period. The maximum changes in the procoagulants occurred on either postoperative day two or day four. The maximum changes in the natural anticoagulants occurred on postoperative day two. There were no significant changes in factor V, factor X, alpha 2-antiplasmin, or platelet aggregability. The timing of the changes coincided with a period of high risk of perioperative myocardial infarction in this group of patients. Thus, it is possible that postoperative hypercoagulability contributes to the development of coronary artery thrombosis and myocardial infarction following abdominal aortic surgery."} {"id": "PMID:1282043", "title": "Isolation and characterization of a sheep cysteine-rich cuticle keratin pseudogene.", "content": "The cysteine-rich keratin proteins of the hair cuticle are derived from a multigene family that has been highly conserved during mammalian evolution. We have recently characterized one cuticle keratin gene isolated from a sheep lambda library, and Southern blot analysis of that clone suggested the presence of a second related gene. In the present paper sequencing of the second gene has now indicated that it is a pseudogene, a finding supported by a lack of expression in vivo. The pseudogene appears to have arisen by gene duplication, possibly from the adjacent functional gene. Key mutations seem to have occurred in the promoter and processing signals of this gene to render it non-functional and two in-frame termination codons are present in the coding region. A possible recombination point between sequences encoding glycine-rich repeats was identified that could have lead to the creation of the in-frame termination codons.", "contents": "Isolation and characterization of a sheep cysteine-rich cuticle keratin pseudogene. The cysteine-rich keratin proteins of the hair cuticle are derived from a multigene family that has been highly conserved during mammalian evolution. We have recently characterized one cuticle keratin gene isolated from a sheep lambda library, and Southern blot analysis of that clone suggested the presence of a second related gene. In the present paper sequencing of the second gene has now indicated that it is a pseudogene, a finding supported by a lack of expression in vivo. The pseudogene appears to have arisen by gene duplication, possibly from the adjacent functional gene. Key mutations seem to have occurred in the promoter and processing signals of this gene to render it non-functional and two in-frame termination codons are present in the coding region. A possible recombination point between sequences encoding glycine-rich repeats was identified that could have lead to the creation of the in-frame termination codons."} {"id": "PMID:1282045", "title": "Comparison of bromine and permanganate as ultrastructural stains for lignin in plants infected by the fungus Colletotrichum lagenarium.", "content": "Transmission electron microscopy (TEM) and energy dispersive X-ray microanalysis (EDS) were used to localize manganese from KMnO4, and bromine, as ultrastructural stains for lignin in an herbaceous plant. The Spookie cultivar of pumpkin is susceptible to infection by the fungus Colletotrichum lagenarium and served as a model system to compare the Br and KMnO4 techniques. Bromine was used in a fixation/staining procedure, and in separate experiments, KMnO4 was used as either a fixative or as a postsection stain. The technique for using bromine was modified from the woody plant procedure by adding a paraformaldehyde prefixation step. With the bromine procedure, cell walls were well-preserved, but the cytoplasm was heavily extracted. The KMnO4 procedures produced well-fixed cytoplasm, but with some staining artifacts. With all procedures, EDS dot mapping demonstrated lignin deposition in the cell walls specifically associated with sites of fungal infection. Lignin was also localized in secondary walls of tracheary elements, sites known to be highly lignified. The bromine procedure provided the most specific localization of lignin with a minimum of artifact. The specific applications of these stains provided data on the ultrastructural localization of lignin which contributed to the elucidation of its role in the interactions between pathogenic fungi in both their resistant and susceptible plant hosts.", "contents": "Comparison of bromine and permanganate as ultrastructural stains for lignin in plants infected by the fungus Colletotrichum lagenarium. Transmission electron microscopy (TEM) and energy dispersive X-ray microanalysis (EDS) were used to localize manganese from KMnO4, and bromine, as ultrastructural stains for lignin in an herbaceous plant. The Spookie cultivar of pumpkin is susceptible to infection by the fungus Colletotrichum lagenarium and served as a model system to compare the Br and KMnO4 techniques. Bromine was used in a fixation/staining procedure, and in separate experiments, KMnO4 was used as either a fixative or as a postsection stain. The technique for using bromine was modified from the woody plant procedure by adding a paraformaldehyde prefixation step. With the bromine procedure, cell walls were well-preserved, but the cytoplasm was heavily extracted. The KMnO4 procedures produced well-fixed cytoplasm, but with some staining artifacts. With all procedures, EDS dot mapping demonstrated lignin deposition in the cell walls specifically associated with sites of fungal infection. Lignin was also localized in secondary walls of tracheary elements, sites known to be highly lignified. The bromine procedure provided the most specific localization of lignin with a minimum of artifact. The specific applications of these stains provided data on the ultrastructural localization of lignin which contributed to the elucidation of its role in the interactions between pathogenic fungi in both their resistant and susceptible plant hosts."} {"id": "PMID:1282046", "title": "Limitations of monastral blue as a vascular label: rapid rate of clearance is age-dependent, and interactions with anesthetics depress arterial blood pressure in rats.", "content": "Monastral blue (MB) has been described as an inexpensive, nontoxic vascular label. Discrepancies as to its rate of removal from circulation and physiological side effects prompted this study in which retention time of MB in the vascular system and effects of MB upon arterial blood pressure with different anesthetics (halothane, isoflurane, and pentobarbital) were measured in rats. Arterial pressure was monitored during intravenous infusion of MB with or without Evans blue, an albumin label. Localized areas of leakage were created by injecting 30 microL of 10(-4) M histamine into abdominal dermis at -2, 0, 5, 7, 10, and 15 minutes from infusion of MB. Mean arterial pressure decreased by 25-30% after MB infusion when halothane or isoflurane was used, but not with pentobarbital. Sites which leaked at 10 and 15 minutes did not usefully label with MB, although Evans blue-labelled albumin appeared in the interstitium. Younger, lighter rats (125-200 vs. 200-250 gm) retained MB longer in circulation, and had a shorter duration of MB-induced hypotension. Spectrophotometric analysis of rat serum showed rapid elimination of MB from the vascular system, with a half-life of 3.5 +/- 1.9 minutes. While MB remains a useful vascular label, its rapid removal from the circulation and its hypotensive effect must be recognized.", "contents": "Limitations of monastral blue as a vascular label: rapid rate of clearance is age-dependent, and interactions with anesthetics depress arterial blood pressure in rats. Monastral blue (MB) has been described as an inexpensive, nontoxic vascular label. Discrepancies as to its rate of removal from circulation and physiological side effects prompted this study in which retention time of MB in the vascular system and effects of MB upon arterial blood pressure with different anesthetics (halothane, isoflurane, and pentobarbital) were measured in rats. Arterial pressure was monitored during intravenous infusion of MB with or without Evans blue, an albumin label. Localized areas of leakage were created by injecting 30 microL of 10(-4) M histamine into abdominal dermis at -2, 0, 5, 7, 10, and 15 minutes from infusion of MB. Mean arterial pressure decreased by 25-30% after MB infusion when halothane or isoflurane was used, but not with pentobarbital. Sites which leaked at 10 and 15 minutes did not usefully label with MB, although Evans blue-labelled albumin appeared in the interstitium. Younger, lighter rats (125-200 vs. 200-250 gm) retained MB longer in circulation, and had a shorter duration of MB-induced hypotension. Spectrophotometric analysis of rat serum showed rapid elimination of MB from the vascular system, with a half-life of 3.5 +/- 1.9 minutes. While MB remains a useful vascular label, its rapid removal from the circulation and its hypotensive effect must be recognized."} {"id": "PMID:1282044", "title": "Resistance to tobacco mosaic virus induced by the 54-kDa gene sequence requires expression of the 54-kDa protein.", "content": "Tobacco plants transformed with the sequence encoding the 54-kDa putative replicase protein of tobacco mosaic virus were resistant to systemic virus disease (D. B. Golemboski, G. P. Lomonossoff, and M. Zaitlin, Proc. Natl. Acad. Sci. USA 87:6311-6315, 1990). Resistance was due to a marked suppression of virus replication at the site of inoculation (J. P. Carr and M. Zaitlin, Mol. Plant-Microbe Interact. 4:579-585, 1991). Although RNA transcripts encoding the 54-kDa protein were present in resistant plants, the 54-kDa protein itself was not observed in vivo. We wished to assess the relative importance of the 54-kDa protein versus its RNA in mediating resistance. Further attempts to detect the 54-kDa protein in plant tissues were unsuccessful; therefore, an indirect approach was taken using a protoplast-based transient gene expression system. Electroporation of protoplasts with plasmids capable of expressing the wild-type 54-kDa protein gene sequence or a mutant lacking the first AUG initiation codon of the 54-kDa open reading frame and encoding a slightly truncated protein reduced virus replication in protoplasts. In contrast, a frameshift mutant that was capable of directing synthesis of a protein only 20% the size of the 54-kDa protein, did not produce resistance in protoplasts. These results show that expression of the 54-kDa protein gene sequence at the RNA level alone is insufficient for resistance, and they implicate the 54-kDa protein itself in mediating this resistance phenomenon.", "contents": "Resistance to tobacco mosaic virus induced by the 54-kDa gene sequence requires expression of the 54-kDa protein. Tobacco plants transformed with the sequence encoding the 54-kDa putative replicase protein of tobacco mosaic virus were resistant to systemic virus disease (D. B. Golemboski, G. P. Lomonossoff, and M. Zaitlin, Proc. Natl. Acad. Sci. USA 87:6311-6315, 1990). Resistance was due to a marked suppression of virus replication at the site of inoculation (J. P. Carr and M. Zaitlin, Mol. Plant-Microbe Interact. 4:579-585, 1991). Although RNA transcripts encoding the 54-kDa protein were present in resistant plants, the 54-kDa protein itself was not observed in vivo. We wished to assess the relative importance of the 54-kDa protein versus its RNA in mediating resistance. Further attempts to detect the 54-kDa protein in plant tissues were unsuccessful; therefore, an indirect approach was taken using a protoplast-based transient gene expression system. Electroporation of protoplasts with plasmids capable of expressing the wild-type 54-kDa protein gene sequence or a mutant lacking the first AUG initiation codon of the 54-kDa open reading frame and encoding a slightly truncated protein reduced virus replication in protoplasts. In contrast, a frameshift mutant that was capable of directing synthesis of a protein only 20% the size of the 54-kDa protein, did not produce resistance in protoplasts. These results show that expression of the 54-kDa protein gene sequence at the RNA level alone is insufficient for resistance, and they implicate the 54-kDa protein itself in mediating this resistance phenomenon."} {"id": "PMID:1282047", "title": "A technique for exposure of the glycoproteic matrix (zona pellucida and mucus) for scanning electron microscopy.", "content": "The fine structure of the zona pellucida (ZP) covering the oocyte and of the mucus covering the surface of the intestinal villi was investigated by using a new method employing ruthenium red (RR), saponin, and osmium-thiocarbohydrazide impregnation. The glycoproteic matrices both appeared constituted by thin filaments (ranging from 22 to 50 nm in thickness) anastomosed to form a very fine network. RR prevented the dissolution and/or alteration of glycoproteins and polyanionic carbohydrates induced by acqueous fixatives. Saponin was a detergent of the soluble proteins. Osmium-thiocarbohydrazide preserved the glycoproteic matrix filaments from the mechanical stress induced by dehydration and critical point drying and reduced filaments packing and shrinkage. The technical improvement was demonstrated by the following results: 1) a regular arrangement of the filaments network; 2) a thickness of mucus filaments smaller than that obtained with other methods of preparation; 3) a homogeneous thickness of ZP filaments. This method allowed a very detailed study of the fine structural organization of the ZP and intestinal mucus. Therefore, this technique can be useful for a better evaluation of the morphodynamic of these and other glycoproteic matrices.", "contents": "A technique for exposure of the glycoproteic matrix (zona pellucida and mucus) for scanning electron microscopy. The fine structure of the zona pellucida (ZP) covering the oocyte and of the mucus covering the surface of the intestinal villi was investigated by using a new method employing ruthenium red (RR), saponin, and osmium-thiocarbohydrazide impregnation. The glycoproteic matrices both appeared constituted by thin filaments (ranging from 22 to 50 nm in thickness) anastomosed to form a very fine network. RR prevented the dissolution and/or alteration of glycoproteins and polyanionic carbohydrates induced by acqueous fixatives. Saponin was a detergent of the soluble proteins. Osmium-thiocarbohydrazide preserved the glycoproteic matrix filaments from the mechanical stress induced by dehydration and critical point drying and reduced filaments packing and shrinkage. The technical improvement was demonstrated by the following results: 1) a regular arrangement of the filaments network; 2) a thickness of mucus filaments smaller than that obtained with other methods of preparation; 3) a homogeneous thickness of ZP filaments. This method allowed a very detailed study of the fine structural organization of the ZP and intestinal mucus. Therefore, this technique can be useful for a better evaluation of the morphodynamic of these and other glycoproteic matrices."} {"id": "PMID:1282048", "title": "Strong influence of the processing of the antigen on negative effects on T cell activation by regions outside the determinant area of bovine alpha s1-casein.", "content": "alpha s1-Casein can elicit a proliferative response in responding T cell clone 3D20 cells (specific for I-Ab plus fragment 136-151), even when using fixed splenic antigen-presenting cells (APC) not carrying antigen processing ability. The order of potency of each tested antigen for fixed APC was the determinant peptide (136-151) > the long peptide (136-195) > the intact protein (199 residues), indicating that regions outside the determinant area negatively affected the stimulatory potency of the antigens. On the other hand, the order for normal splenic APC was the short peptide > the intact protein > the long peptide. This shows that negative effects by regions outside the determinant area were strongly influenced by the antigen processing.", "contents": "Strong influence of the processing of the antigen on negative effects on T cell activation by regions outside the determinant area of bovine alpha s1-casein. alpha s1-Casein can elicit a proliferative response in responding T cell clone 3D20 cells (specific for I-Ab plus fragment 136-151), even when using fixed splenic antigen-presenting cells (APC) not carrying antigen processing ability. The order of potency of each tested antigen for fixed APC was the determinant peptide (136-151) > the long peptide (136-195) > the intact protein (199 residues), indicating that regions outside the determinant area negatively affected the stimulatory potency of the antigens. On the other hand, the order for normal splenic APC was the short peptide > the intact protein > the long peptide. This shows that negative effects by regions outside the determinant area were strongly influenced by the antigen processing."} {"id": "PMID:1282049", "title": "Chitinous components of the cell wall of Fusarium oxysporum.", "content": "The cell wall of Fusarium oxysporum f. sp. lycopersici was digested with chitinase to analyze the structure of its chitinous components. In spite of a similar acetylation degree of the cell wall components to that of 25-35% acetylated chitosan, only N-acetylglucosamine disaccharide [(GlcNAc)2] was obtained from chitinase hydrolyzate of the fungal cell wall by CM-Sephadex C-25 column chromatography, while (GlcNAc)2 and several types of deacetylated chitooligosaccharides were separated from that of 25-35% acetylated chitosan. The results indicate that N-acetylglucosamine residues in the polysaccharide chains of the fungal cell wall are most likely condensed into some region, while acetylated residues are more scattered in 25-35% acetylated chitosan.", "contents": "Chitinous components of the cell wall of Fusarium oxysporum. The cell wall of Fusarium oxysporum f. sp. lycopersici was digested with chitinase to analyze the structure of its chitinous components. In spite of a similar acetylation degree of the cell wall components to that of 25-35% acetylated chitosan, only N-acetylglucosamine disaccharide [(GlcNAc)2] was obtained from chitinase hydrolyzate of the fungal cell wall by CM-Sephadex C-25 column chromatography, while (GlcNAc)2 and several types of deacetylated chitooligosaccharides were separated from that of 25-35% acetylated chitosan. The results indicate that N-acetylglucosamine residues in the polysaccharide chains of the fungal cell wall are most likely condensed into some region, while acetylated residues are more scattered in 25-35% acetylated chitosan."} {"id": "PMID:1282050", "title": "In vitro interactions of Pseudomonas RNA polymerases with tac and RNA I promoters.", "content": "The activities of RNA polymerases from Pseudomonas putida and Pseudomonas aeruginosa were compared with that of Escherichia coli RNA polymerase in an in vitro transcription system. All three enzymes initiated transcription at the tac promoter and the RNA I promoter of E. coli. We measured the rate of open complex formation between the RNA polymerases and the promoters, and the saturation level of open complex formation at equilibrium in single-round transcription. The relative rates of open complex formation were P. putida > E. coli > P. aeruginosa and the relative saturation levels of open complex formation at equilibrium were E. coli > P. putida > P. aeruginosa for the tac and RNA I promoters. The interaction of the RNA polymerases with the promoters was also studied by DNase I footprinting. The patterns of protection of the Pseudomonas RNA polymerases on the tac promoter were similar to that of E. coli RNA polymerase. However, the protection patterns of the Pseudomonas RNA polymerases on the RNA I promoter were slightly different from that of E. coli RNA polymerase.", "contents": "In vitro interactions of Pseudomonas RNA polymerases with tac and RNA I promoters. The activities of RNA polymerases from Pseudomonas putida and Pseudomonas aeruginosa were compared with that of Escherichia coli RNA polymerase in an in vitro transcription system. All three enzymes initiated transcription at the tac promoter and the RNA I promoter of E. coli. We measured the rate of open complex formation between the RNA polymerases and the promoters, and the saturation level of open complex formation at equilibrium in single-round transcription. The relative rates of open complex formation were P. putida > E. coli > P. aeruginosa and the relative saturation levels of open complex formation at equilibrium were E. coli > P. putida > P. aeruginosa for the tac and RNA I promoters. The interaction of the RNA polymerases with the promoters was also studied by DNase I footprinting. The patterns of protection of the Pseudomonas RNA polymerases on the tac promoter were similar to that of E. coli RNA polymerase. However, the protection patterns of the Pseudomonas RNA polymerases on the RNA I promoter were slightly different from that of E. coli RNA polymerase."} {"id": "PMID:1282051", "title": "Specific measurement of a major mite allergen, Der f II, by an enzyme-linked immunosorbent assay system using monoclonal anti-Der f II antibodies.", "content": "An enzyme linked immunosorbent assay system using a monoclonal antibody, 15E11, specific for a major allergen Der f II in house dust mite, was developed. This system detected only Der f II in the presence of Der p II and other allergens. The Der f II contents in several house dust samples significantly correlated with the numbers of the mites in the same house dust samples (n = 14, r = 0.88, p < 0.001). These data showed that this system was useful for specific measurement of Der f II in house dusts.", "contents": "Specific measurement of a major mite allergen, Der f II, by an enzyme-linked immunosorbent assay system using monoclonal anti-Der f II antibodies. An enzyme linked immunosorbent assay system using a monoclonal antibody, 15E11, specific for a major allergen Der f II in house dust mite, was developed. This system detected only Der f II in the presence of Der p II and other allergens. The Der f II contents in several house dust samples significantly correlated with the numbers of the mites in the same house dust samples (n = 14, r = 0.88, p < 0.001). These data showed that this system was useful for specific measurement of Der f II in house dusts."} {"id": "PMID:1282052", "title": "Substrate specificity of the Trypanosoma cruzi trans-sialidase.", "content": "Trypanosoma cruzi trypomastigotes acquire sialic acid (SA) from host glycoconjugates by means of a plasma membrane-associated trans-sialidase (TS). Here we study the substrate specificity of TS, which differs from all known sialyltransferases in that it does not require cytidine monophosphate (CMP)-SA as donor. The T. cruzi TS reversibly transfers SA to saccharides with terminal beta-Gal (but not alpha-Gal) residues. Donors are saccharides with SA linked to terminal beta-Gal residues by (alpha 2-3), but not (alpha 2-6) bonds. The type of beta-linkage of the terminal Gal residue is of minor importance (beta 1-4 and beta 1-6 are slightly better than beta 1-3), whereas chain length and the structure of additional vicinal sugar residues are not relevant. SA on the surface of living trypomastigotes of T. cruzi is transferred back and forth between the parasite surface and acceptor molecules with terminal beta-Gal, either in solution or on the surface of neighbouring mammalian cells. Addition of fucose residue on or close to the terminal galactose impairs TS activity. As a consequence, the enzyme acts poorly on the E-selectin ligand sialyl-Lewisx and its precursor Lewisx, and in vitro adhesion of TS-treated neutrophils to L-cells expressing L-selectin is not affected. Modifications in the structure of the (alpha 2-3)-linked N-acetyl-neuraminic acid (Neu5Ac) (deoxy or methoxy) of the donor molecules do not impair transfer if the changes are at C9, whereas changes at C4, C7 and C8 impair the ability to donate the modified SA.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Substrate specificity of the Trypanosoma cruzi trans-sialidase. Trypanosoma cruzi trypomastigotes acquire sialic acid (SA) from host glycoconjugates by means of a plasma membrane-associated trans-sialidase (TS). Here we study the substrate specificity of TS, which differs from all known sialyltransferases in that it does not require cytidine monophosphate (CMP)-SA as donor. The T. cruzi TS reversibly transfers SA to saccharides with terminal beta-Gal (but not alpha-Gal) residues. Donors are saccharides with SA linked to terminal beta-Gal residues by (alpha 2-3), but not (alpha 2-6) bonds. The type of beta-linkage of the terminal Gal residue is of minor importance (beta 1-4 and beta 1-6 are slightly better than beta 1-3), whereas chain length and the structure of additional vicinal sugar residues are not relevant. SA on the surface of living trypomastigotes of T. cruzi is transferred back and forth between the parasite surface and acceptor molecules with terminal beta-Gal, either in solution or on the surface of neighbouring mammalian cells. Addition of fucose residue on or close to the terminal galactose impairs TS activity. As a consequence, the enzyme acts poorly on the E-selectin ligand sialyl-Lewisx and its precursor Lewisx, and in vitro adhesion of TS-treated neutrophils to L-cells expressing L-selectin is not affected. Modifications in the structure of the (alpha 2-3)-linked N-acetyl-neuraminic acid (Neu5Ac) (deoxy or methoxy) of the donor molecules do not impair transfer if the changes are at C9, whereas changes at C4, C7 and C8 impair the ability to donate the modified SA.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282053", "title": "The use of hetastarch for plasma expansion.", "content": "The use of colloids in hypo-oncotic individuals to increase plasma volume has been shown to have distinct and consistent advantages compared with the use of crystalloid fluids. Colloids increase plasma colloid oncotic pressure, whereas crystalloids decrease it, an effect that can be extremely detrimental in individuals with low basal plasma colloid oncotic pressure. Increasing plasma volume in hypo-oncotic individuals without inducing large increases in interstitial water content is difficult when crystalloid fluids are used. However, colloids have much better plasma volume expansion ability without the induction of concurrent increases in interstitial water content, even in hypooncotic individuals. Review of the literature indicates that hetastarch is an extremely safe colloid for acute and long-term use in humans and dogs. Its excellent safety record probably is attributable to its structural analogy to the natural compound glycogen. The lack of availability of a substance analogous to human 5% serum albumin and the scarcity of plasma in veterinary medicine leaves hetastarch as the safest option of available colloids. Its ability to increase plasma volume and colloid oncotic pressure is equal to or better than dextran 70 and 5% albumin and is clearly better than plasma or whole blood. Increases in plasma volume and colloid oncotic pressure usually last approximately 48 hours after a single injection, but the duration of increases significantly after multiple infusions. Contraindications to its use include heart failure and oliguric renal failure, because of its excellent ability to increase plasma volume, and the presence of von Willebrand's disease, because of its ability to significantly lower all components of Factor VIII-related complex in humans.", "contents": "The use of hetastarch for plasma expansion. The use of colloids in hypo-oncotic individuals to increase plasma volume has been shown to have distinct and consistent advantages compared with the use of crystalloid fluids. Colloids increase plasma colloid oncotic pressure, whereas crystalloids decrease it, an effect that can be extremely detrimental in individuals with low basal plasma colloid oncotic pressure. Increasing plasma volume in hypo-oncotic individuals without inducing large increases in interstitial water content is difficult when crystalloid fluids are used. However, colloids have much better plasma volume expansion ability without the induction of concurrent increases in interstitial water content, even in hypooncotic individuals. Review of the literature indicates that hetastarch is an extremely safe colloid for acute and long-term use in humans and dogs. Its excellent safety record probably is attributable to its structural analogy to the natural compound glycogen. The lack of availability of a substance analogous to human 5% serum albumin and the scarcity of plasma in veterinary medicine leaves hetastarch as the safest option of available colloids. Its ability to increase plasma volume and colloid oncotic pressure is equal to or better than dextran 70 and 5% albumin and is clearly better than plasma or whole blood. Increases in plasma volume and colloid oncotic pressure usually last approximately 48 hours after a single injection, but the duration of increases significantly after multiple infusions. Contraindications to its use include heart failure and oliguric renal failure, because of its excellent ability to increase plasma volume, and the presence of von Willebrand's disease, because of its ability to significantly lower all components of Factor VIII-related complex in humans."} {"id": "PMID:1282054", "title": "Radical lymphadenectomy for rectal cancer facilitated by a carbon particle infusion lymphangiography.", "content": "For the intraoperative visualization of the para-aortic nodes and those around the iliac vessels, a fine carbon particle solution was infused into the bilateral pedal lymphatic vessels of 12 patients with rectal carcinoma. A low anterior resection with radical lymph node dissection was then performed while preserving pelvic autonomic nerves. Of 444 lymph nodes removed from the iliac arterial region, 430 were stained with carbon black (96.8%), even though the black staining was not perfect in the nodes of the inferior mesenteric arterial region. All of the lateral black stained nodes were clearly visible and hence could be easily excised. The average number of dissected nodes in one patient was 43.8 in this dissection with carbon particle infusion, which was larger than those of conventional lymph node dissection. We then examined the length of time that a postoperative indwelling bladder catheter was needed as an indication for autonomic nerve damage, and it was ascertained that less damage occurred in this operation compared to other types of dissections, such as conventional or extended lymph node dissection.", "contents": "Radical lymphadenectomy for rectal cancer facilitated by a carbon particle infusion lymphangiography. For the intraoperative visualization of the para-aortic nodes and those around the iliac vessels, a fine carbon particle solution was infused into the bilateral pedal lymphatic vessels of 12 patients with rectal carcinoma. A low anterior resection with radical lymph node dissection was then performed while preserving pelvic autonomic nerves. Of 444 lymph nodes removed from the iliac arterial region, 430 were stained with carbon black (96.8%), even though the black staining was not perfect in the nodes of the inferior mesenteric arterial region. All of the lateral black stained nodes were clearly visible and hence could be easily excised. The average number of dissected nodes in one patient was 43.8 in this dissection with carbon particle infusion, which was larger than those of conventional lymph node dissection. We then examined the length of time that a postoperative indwelling bladder catheter was needed as an indication for autonomic nerve damage, and it was ascertained that less damage occurred in this operation compared to other types of dissections, such as conventional or extended lymph node dissection."} {"id": "PMID:1282055", "title": "Growth and survival of Pseudomonas cepacia DBO1 (pRO101) in soil amended with 2,4-dichlorophenoxyacetic acid.", "content": "The 2,4-dichlorophenoxyacetic acid (2,4-D) degrading pseudomonad, Pseudomonas cepacia DBO1(pRO101), was inoculated at approximately 10(7) CFU/g into sterile and non-sterile soil amended with 0, 5 or 500 ppm 2,4-D and the survival of the strain was studied for a period of 44 days. In general, the strain survived best in sterile soil. When the sterile soil was amended with 2,4-D, the strain survived at a significantly higher level than in non-amended sterile soil. In non-sterile soil either non-amended or amended with 5 ppm 2,4-D the strain died out, whereas with 500 ppm 2,4-D the strain only declined one order of magnitude through the 44 days. The influence of 0, 0.06, 12 and 600 ppm 2,4-D on short-term (48 h) survival of P. cepacia DBO1(pRO101) inoculated to a level of 6 x 10(4), 6 x 10(6) or 1 x 10(8) CFU/g soil was studied in non-sterile soil. Both inoculum level and 2,4-D concentration were found to have a positive influence on numbers of P. cepacia DBO1(pRO101). At 600 ppm 2,4-D growth was significant irrespective of the inoculation level, and at 12 ppm growth was stimulated at the two lowest inocula levels. P. cepacia DBO1(pRO101) was able to survive for 15 months in sterile buffers kept at room temperature. During this starvation, cells shrunk to about one third the volume of exponentially growing cells.", "contents": "Growth and survival of Pseudomonas cepacia DBO1 (pRO101) in soil amended with 2,4-dichlorophenoxyacetic acid. The 2,4-dichlorophenoxyacetic acid (2,4-D) degrading pseudomonad, Pseudomonas cepacia DBO1(pRO101), was inoculated at approximately 10(7) CFU/g into sterile and non-sterile soil amended with 0, 5 or 500 ppm 2,4-D and the survival of the strain was studied for a period of 44 days. In general, the strain survived best in sterile soil. When the sterile soil was amended with 2,4-D, the strain survived at a significantly higher level than in non-amended sterile soil. In non-sterile soil either non-amended or amended with 5 ppm 2,4-D the strain died out, whereas with 500 ppm 2,4-D the strain only declined one order of magnitude through the 44 days. The influence of 0, 0.06, 12 and 600 ppm 2,4-D on short-term (48 h) survival of P. cepacia DBO1(pRO101) inoculated to a level of 6 x 10(4), 6 x 10(6) or 1 x 10(8) CFU/g soil was studied in non-sterile soil. Both inoculum level and 2,4-D concentration were found to have a positive influence on numbers of P. cepacia DBO1(pRO101). At 600 ppm 2,4-D growth was significant irrespective of the inoculation level, and at 12 ppm growth was stimulated at the two lowest inocula levels. P. cepacia DBO1(pRO101) was able to survive for 15 months in sterile buffers kept at room temperature. During this starvation, cells shrunk to about one third the volume of exponentially growing cells."} {"id": "PMID:1282057", "title": "Analysis of Tat transactivation of human immunodeficiency virus transcription in vitro.", "content": "The HIV Tat protein is a potent transactivator of HIV transcription, increasing both RNA initiation and elongation. We now demonstrate that purified, full-length 86 amino acid Tat protein specifically transactivates the HIV LTR in vitro to a high level (25- to 60-fold). Tat transactivation was specifically blocked by anti-Tat serum, but not preimmune serum. Tat did not transactivate transcription from the control adenovirus major late promoter (AdMLP). HIV transcription was blocked at various functional steps during initiation and elongation complex formation. Similar to the control AdMLP, HIV basal initiation complex assembly was sensitive to the addition of 0.015% sarkosyl prior to the addition of nucleoside triphosphates. Resistance to 0.05% sarkosyl required the addition of G, C, and U, which constitute the first 13 bases of the HIV RNA transcript. The addition of Tat to the in vitro transcription relieved the 0.015% sarkosyl block. These Tat-induced complexes were sensitive to 0.05% sarkosyl, suggesting that transcriptional initiation had not occurred. Consistent with this hypothesis, the addition of G, C, and U to the Tat-induced transcription complexes allowed the rapid conversion to transcription initiation complexes. Tat also facilitated the formation of 0.015% sarkosyl-resistant complexes in a reconstituted transcription system containing partially purified transcription factors and polymerase II. Following the formation of stable initiation complexes, Tat increased the rate and efficiency of transcription elongation on the HIV but not the AdML template. Kinetic analysis of Tat transactivation suggests that approximately 30% of the Tat initiation complexes are converted to elongation complexes. We conclude that Tat, in addition to its demonstrated role in RNA elongation, facilitates transcription initiation in vitro.", "contents": "Analysis of Tat transactivation of human immunodeficiency virus transcription in vitro. The HIV Tat protein is a potent transactivator of HIV transcription, increasing both RNA initiation and elongation. We now demonstrate that purified, full-length 86 amino acid Tat protein specifically transactivates the HIV LTR in vitro to a high level (25- to 60-fold). Tat transactivation was specifically blocked by anti-Tat serum, but not preimmune serum. Tat did not transactivate transcription from the control adenovirus major late promoter (AdMLP). HIV transcription was blocked at various functional steps during initiation and elongation complex formation. Similar to the control AdMLP, HIV basal initiation complex assembly was sensitive to the addition of 0.015% sarkosyl prior to the addition of nucleoside triphosphates. Resistance to 0.05% sarkosyl required the addition of G, C, and U, which constitute the first 13 bases of the HIV RNA transcript. The addition of Tat to the in vitro transcription relieved the 0.015% sarkosyl block. These Tat-induced complexes were sensitive to 0.05% sarkosyl, suggesting that transcriptional initiation had not occurred. Consistent with this hypothesis, the addition of G, C, and U to the Tat-induced transcription complexes allowed the rapid conversion to transcription initiation complexes. Tat also facilitated the formation of 0.015% sarkosyl-resistant complexes in a reconstituted transcription system containing partially purified transcription factors and polymerase II. Following the formation of stable initiation complexes, Tat increased the rate and efficiency of transcription elongation on the HIV but not the AdML template. Kinetic analysis of Tat transactivation suggests that approximately 30% of the Tat initiation complexes are converted to elongation complexes. We conclude that Tat, in addition to its demonstrated role in RNA elongation, facilitates transcription initiation in vitro."} {"id": "PMID:1282058", "title": "Characterization of the subtype of muscarinic receptor coupled to the stimulation of phosphoinositide hydrolysis in 132-1N1 human astrocytoma cells.", "content": "Stimulation of muscarinic receptors increases phosphoinositide (PI) hydrolysis in 132-1N1 human astrocytoma cells. To evaluate the subtype of receptors which mediate PI hydrolysis in 132-1N1 cells, the effects of: a) the nonselective M1 agonist, carbachol; b) the selective M1 agonist, 4-hydroxy-2-butynyl-trimethylammonium chloride-m-chlorocarbinilate (McN-343); c) the nonselective antagonists, atropine and scopolamine; d) the relatively selective M1 antagonist, pirenzepine; e) the relatively selective M2 antagonists, AF-DX 116 (11-2-diethylaminomethyl-1-piperidinylacetyl-5, 11-dihydro-6H-pyrido-2,3-b-1,4-benzodiazepine-6-one) and methoctramine and f) the relatively selective M3 antagonist, hexahydrosila-difenidol (HHSiD) on PI hydrolysis in 132-1N1 cells were studied. The cell pools of inositol-phospholipids were prelabelled by incubating 132-1N1 cells in a low inositol containing medium (CMRL-1066) supplemented with [3H]inositol (2 microCi/ml) for 20-24 hours at 37 degrees C. The cells were washed and resuspended in a physiological salt solution, and PI hydrolysis was measured by accumulation of [3H]inositol-1-phosphate (IP) in the presence of 10 mM LiCl. Carbachol produced time and concentration dependent PI hydrolysis (EC50, 37 microM). McN-A343 did not cause significant hydrolysis of PI in 132-1N1 cells indicating that the receptor was not of M1 type. All the above muscarinic antagonists caused a concentration dependent decrease in the level of IP in response to carbachol (100 microM). The rank order of their affinities (pA2 values) was: atropine (8.8) > HHSiD (7.6) > pirenzepine (6.8) > methoctramine (6.0) > AF-DX 116 (5.8). This rank order supports the concept that M3 (other names, M2 beta, glandular M2) receptors are linked to PI hydrolysis in 132-1N1 cells. HHSiD, which is selective for M3 receptors of the smooth muscle has higher affinity for muscarinic receptors in 132-1N1 cells than AF-DX 116 which is selective for M2 receptors in cardiac tissue. If the receptor in 132-1N1 cells had been M2, part of the rank order for affinities would have been methoctramine > AF-DX 116 > HHSiD > pirenzepine. From all of these observations, the muscarinic receptor for PI hydrolysis in 132-1N1 cells is tentatively characterized as of M3 type.", "contents": "Characterization of the subtype of muscarinic receptor coupled to the stimulation of phosphoinositide hydrolysis in 132-1N1 human astrocytoma cells. Stimulation of muscarinic receptors increases phosphoinositide (PI) hydrolysis in 132-1N1 human astrocytoma cells. To evaluate the subtype of receptors which mediate PI hydrolysis in 132-1N1 cells, the effects of: a) the nonselective M1 agonist, carbachol; b) the selective M1 agonist, 4-hydroxy-2-butynyl-trimethylammonium chloride-m-chlorocarbinilate (McN-343); c) the nonselective antagonists, atropine and scopolamine; d) the relatively selective M1 antagonist, pirenzepine; e) the relatively selective M2 antagonists, AF-DX 116 (11-2-diethylaminomethyl-1-piperidinylacetyl-5, 11-dihydro-6H-pyrido-2,3-b-1,4-benzodiazepine-6-one) and methoctramine and f) the relatively selective M3 antagonist, hexahydrosila-difenidol (HHSiD) on PI hydrolysis in 132-1N1 cells were studied. The cell pools of inositol-phospholipids were prelabelled by incubating 132-1N1 cells in a low inositol containing medium (CMRL-1066) supplemented with [3H]inositol (2 microCi/ml) for 20-24 hours at 37 degrees C. The cells were washed and resuspended in a physiological salt solution, and PI hydrolysis was measured by accumulation of [3H]inositol-1-phosphate (IP) in the presence of 10 mM LiCl. Carbachol produced time and concentration dependent PI hydrolysis (EC50, 37 microM). McN-A343 did not cause significant hydrolysis of PI in 132-1N1 cells indicating that the receptor was not of M1 type. All the above muscarinic antagonists caused a concentration dependent decrease in the level of IP in response to carbachol (100 microM). The rank order of their affinities (pA2 values) was: atropine (8.8) > HHSiD (7.6) > pirenzepine (6.8) > methoctramine (6.0) > AF-DX 116 (5.8). This rank order supports the concept that M3 (other names, M2 beta, glandular M2) receptors are linked to PI hydrolysis in 132-1N1 cells. HHSiD, which is selective for M3 receptors of the smooth muscle has higher affinity for muscarinic receptors in 132-1N1 cells than AF-DX 116 which is selective for M2 receptors in cardiac tissue. If the receptor in 132-1N1 cells had been M2, part of the rank order for affinities would have been methoctramine > AF-DX 116 > HHSiD > pirenzepine. From all of these observations, the muscarinic receptor for PI hydrolysis in 132-1N1 cells is tentatively characterized as of M3 type."} {"id": "PMID:1282056", "title": "Mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) in soil inoculated with Pseudomonas cepacia DBO1(pRO101), Alcaligenes eutrophus AEO106(pRO101) and Alcaligenes eutrophus JMP134(pJP4): effects of inoculation level and substrate concentration.", "content": "Mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) by two Alcaligenes eutrophus strains and one Pseudomonas cepacia strain containing the 2,4-D degrading plasmids pJP4 or pRO101 (= pJP4::Tn1721) was tested in 50 g (wet wt) samples of non-sterile soil. Mineralization was measured as 14C-CO2 evolved during degradation of uniformly-ring-labelled 14C-2,4-D. When the strains were inoculated to a level of approximately 10(8) CFU/g soil, between 20 and 45% of the added 2,4-D (0.05 ppm, 10 ppm or 500 ppm) was mineralized within 72 h. Mineralization of 0.05 ppm and 10 ppm 2,4-D by the two A. eutrophus strains was identical and rapid whereas mineralization by P. cepacia DBO1(pRO101) occurred more slowly. In contrast, mineralization of 500 ppm 2,4-D by the two A. eutrophus strains was very slow whereas mineralization by P. cepacia DBO1 was more rapid. Comparison of 2,4-D mineralization at different levels of inoculation with P. cepacia DBO1(pRO101) (6 x 10(4), 6 x 10(6) and 1 x 10(8) CFU/g soil) revealed that the maximum mineralization rate was reached earlier with the high inoculation levels than with the low level. The kinetics of mineralization were evaluated by nonlinear regression analysis using five different models. The linear or the logarithmic form of a three-half-order model were found to be the most appropriate models for describing 2,4-D mineralization in soil. In the cases in which the logarithmic form of the three-half-order model was the most appropriate model we found, in accordance with the assumptions of the model, a significant growth of the inoculated strains.", "contents": "Mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) in soil inoculated with Pseudomonas cepacia DBO1(pRO101), Alcaligenes eutrophus AEO106(pRO101) and Alcaligenes eutrophus JMP134(pJP4): effects of inoculation level and substrate concentration. Mineralization of 2,4-dichlorophenoxyacetic acid (2,4-D) by two Alcaligenes eutrophus strains and one Pseudomonas cepacia strain containing the 2,4-D degrading plasmids pJP4 or pRO101 (= pJP4::Tn1721) was tested in 50 g (wet wt) samples of non-sterile soil. Mineralization was measured as 14C-CO2 evolved during degradation of uniformly-ring-labelled 14C-2,4-D. When the strains were inoculated to a level of approximately 10(8) CFU/g soil, between 20 and 45% of the added 2,4-D (0.05 ppm, 10 ppm or 500 ppm) was mineralized within 72 h. Mineralization of 0.05 ppm and 10 ppm 2,4-D by the two A. eutrophus strains was identical and rapid whereas mineralization by P. cepacia DBO1(pRO101) occurred more slowly. In contrast, mineralization of 500 ppm 2,4-D by the two A. eutrophus strains was very slow whereas mineralization by P. cepacia DBO1 was more rapid. Comparison of 2,4-D mineralization at different levels of inoculation with P. cepacia DBO1(pRO101) (6 x 10(4), 6 x 10(6) and 1 x 10(8) CFU/g soil) revealed that the maximum mineralization rate was reached earlier with the high inoculation levels than with the low level. The kinetics of mineralization were evaluated by nonlinear regression analysis using five different models. The linear or the logarithmic form of a three-half-order model were found to be the most appropriate models for describing 2,4-D mineralization in soil. In the cases in which the logarithmic form of the three-half-order model was the most appropriate model we found, in accordance with the assumptions of the model, a significant growth of the inoculated strains."} {"id": "PMID:1282059", "title": "Exogenously added free phosphotyrosine induces aggregation of circulating platelets in rabbits.", "content": "When free phosphotyrosine is injected into rabbits, circulating aggregated platelets are readily observed in concomitance with altered electrocardiographic profiles. Since phosphotyrosine is also able to induce platelet aggregation in vitro, altogether these results suggest that free phosphotyrosine in blood could be meaningful for in vivo platelet activation.", "contents": "Exogenously added free phosphotyrosine induces aggregation of circulating platelets in rabbits. When free phosphotyrosine is injected into rabbits, circulating aggregated platelets are readily observed in concomitance with altered electrocardiographic profiles. Since phosphotyrosine is also able to induce platelet aggregation in vitro, altogether these results suggest that free phosphotyrosine in blood could be meaningful for in vivo platelet activation."} {"id": "PMID:1282060", "title": "Further characterization of RNA-dependent-DNA polymerase activity in human gastric cancer.", "content": "Based upon our previous report indicating the presence of retrovirus-like particles in human gastric cancer cells, we analyzed the putative endogenous reverse transcriptase activity these particles should have. To evaluate the specificity of reverse transcription over that displayed by normal cellular DNA polymerases, the following discriminatory criteria were used: 1) resistance to high concentrations of Actinomycin D; 2) sensitivity to preincubation with ribonuclease A; 3) behavior in cesium sulfate isopycnic gradients and 4) size-shifting of putative template-product complexes after RNase exposure in agarose gel electrophoresis. We report a significant endogenous reverse transcriptase activity associated with membrane-encapsidated particles from terminally-illed patients but not in normal counterparts. Although these structures closely resemble retro viruses, a new model is proposed to explain our findings.", "contents": "Further characterization of RNA-dependent-DNA polymerase activity in human gastric cancer. Based upon our previous report indicating the presence of retrovirus-like particles in human gastric cancer cells, we analyzed the putative endogenous reverse transcriptase activity these particles should have. To evaluate the specificity of reverse transcription over that displayed by normal cellular DNA polymerases, the following discriminatory criteria were used: 1) resistance to high concentrations of Actinomycin D; 2) sensitivity to preincubation with ribonuclease A; 3) behavior in cesium sulfate isopycnic gradients and 4) size-shifting of putative template-product complexes after RNase exposure in agarose gel electrophoresis. We report a significant endogenous reverse transcriptase activity associated with membrane-encapsidated particles from terminally-illed patients but not in normal counterparts. Although these structures closely resemble retro viruses, a new model is proposed to explain our findings."} {"id": "PMID:1282061", "title": "Light microscopical demonstration of non-specific alkaline phosphatase activity with an incubation medium containing cerium and two calcium as the capturing agents. The cerium/calcium-hydrogen peroxide-P-phenylenediamine/pyrocatechol (Ce/Ca-H2O2-PPD/PC) double capture technique.", "content": "A new method for the light microscopical demonstration of alPase activity in cryotome sections by using simultaneously cerium and calcium as capturing agents (double capture technique) is described. This method has an increased sensitivity compared with the single cerium-based and the Gomori based-cerium (single calcium and cerium converted) with techniques described previously. Presuming that the enzymatic activity during incubation of sections in the presence of a defined capturing agent is constant, the increased sensitivity after employment of the double capture method could be attributed to a decrease of enzyme inhibition by cerium through the presence of calcium. Based on model experiments it is assumed that calcium phosphate and cerium phosphate are the primary reaction products, the former converting into cerium phosphate already during incubation. The remaining calcium phosphate is converted completely by treatment with cerium citrate solution (conversion reaction). After oxidation with H2O2 the cerium perhydroxyphosphate was visualized in a paraphenylenediamine/pyrocatechol (Hanker-Yates reagent) solution without H2O2 to give a black reaction product. This visualization procedure is superior to the DAB or DAB-Ni mode as published earlier. Some results concerning the mode of inhibition of the pseudoperoxidase activity of the hemoglobin are presented.", "contents": "Light microscopical demonstration of non-specific alkaline phosphatase activity with an incubation medium containing cerium and two calcium as the capturing agents. The cerium/calcium-hydrogen peroxide-P-phenylenediamine/pyrocatechol (Ce/Ca-H2O2-PPD/PC) double capture technique. A new method for the light microscopical demonstration of alPase activity in cryotome sections by using simultaneously cerium and calcium as capturing agents (double capture technique) is described. This method has an increased sensitivity compared with the single cerium-based and the Gomori based-cerium (single calcium and cerium converted) with techniques described previously. Presuming that the enzymatic activity during incubation of sections in the presence of a defined capturing agent is constant, the increased sensitivity after employment of the double capture method could be attributed to a decrease of enzyme inhibition by cerium through the presence of calcium. Based on model experiments it is assumed that calcium phosphate and cerium phosphate are the primary reaction products, the former converting into cerium phosphate already during incubation. The remaining calcium phosphate is converted completely by treatment with cerium citrate solution (conversion reaction). After oxidation with H2O2 the cerium perhydroxyphosphate was visualized in a paraphenylenediamine/pyrocatechol (Hanker-Yates reagent) solution without H2O2 to give a black reaction product. This visualization procedure is superior to the DAB or DAB-Ni mode as published earlier. Some results concerning the mode of inhibition of the pseudoperoxidase activity of the hemoglobin are presented."} {"id": "PMID:1282062", "title": "Late cardiovascular and pulmonary complications of therapy in Hodgkin's disease: report of three unusual cases, with a review of relevant literature.", "content": "With the advent of modern therapeutic approaches, even patients with advanced Hodgkin's disease have high cure rates today. Therefore, more attention is gradually being focused upon the late complications of chemotherapy and irradiation, appearing long after the patient is in remission and thought to be cured. In this report, we review the incidence and presentation of some of the cardiovascular and pulmonary complications which may appear later in the course of the disease. Cardiovascular mishaps reviewed include pericardial manifestations, conduction abnormalities, cardiomyopathy, and premature coronary artery disease. Pulmonary complications discussed are lung fibrosis, spontaneous pneumothorax, pulmonary veno-occlusive disease, and hyperlucent lung. Three instructive cases from our recent experience, are also presented. One fatal case was due to cardiac failure because of radiation-induced pericarditis and coronary artery disease. Another patient with an almost fatal complication required lung transplantation because of severe bilateral radiation fibrosis of the lung and pulmonary veno-occlusive disease. The third instance was also life-threatening in nature, with radiation-induced arterial changes in the major arteries of the chest and neck, resulting in recurrent cerebral and ophthalmic thromboembolic disease. It is suggested that potentially severe cardiopulmonary complications be considered during the planning of the initial and subsequent management of patients with Hodgkin's disease, particularly in an era employing autologous and allogeneic bone marrow transplantation as part of therapy in some cases.", "contents": "Late cardiovascular and pulmonary complications of therapy in Hodgkin's disease: report of three unusual cases, with a review of relevant literature. With the advent of modern therapeutic approaches, even patients with advanced Hodgkin's disease have high cure rates today. Therefore, more attention is gradually being focused upon the late complications of chemotherapy and irradiation, appearing long after the patient is in remission and thought to be cured. In this report, we review the incidence and presentation of some of the cardiovascular and pulmonary complications which may appear later in the course of the disease. Cardiovascular mishaps reviewed include pericardial manifestations, conduction abnormalities, cardiomyopathy, and premature coronary artery disease. Pulmonary complications discussed are lung fibrosis, spontaneous pneumothorax, pulmonary veno-occlusive disease, and hyperlucent lung. Three instructive cases from our recent experience, are also presented. One fatal case was due to cardiac failure because of radiation-induced pericarditis and coronary artery disease. Another patient with an almost fatal complication required lung transplantation because of severe bilateral radiation fibrosis of the lung and pulmonary veno-occlusive disease. The third instance was also life-threatening in nature, with radiation-induced arterial changes in the major arteries of the chest and neck, resulting in recurrent cerebral and ophthalmic thromboembolic disease. It is suggested that potentially severe cardiopulmonary complications be considered during the planning of the initial and subsequent management of patients with Hodgkin's disease, particularly in an era employing autologous and allogeneic bone marrow transplantation as part of therapy in some cases."} {"id": "PMID:1282063", "title": "Capability of various cytokines to induce quiescent myeloid leukemia cells to the proliferative stage.", "content": "In order to investigate the capability of cytokines to induce myeloid leukemia cells from G0 phase to the proliferative stage, blasts from 9 patients with AML and 1 patient with CML-MC were cultured with various cytokines (IL-3, GM-CSF, IL-3 + GM-CSF, G-CSF) for 48 hours or 96 hours in a serum-free culture system. Cells were analyzed by two-color flow cytometry, using PI and the monoclonal antibody Ki-67. The percentage of cells in G0 phase was reduced significantly when the cells were cultured with IL-3 (p < 0.01), GM-CSF (p < 0.01), and IL-3 + GM-CSF (p < 0.01) for 48 hours, as compared with the percentage of cells in G0 phase before culture. Moreover, the percentage of cells in S phase increased significantly when the cells were cultured with IL-3 (p < 0.01), GM-CSF (p < 0.02), and IL-3 + GM-CSF (p < 0.01) for 48 hours, as compared with the percentage of cells in S phase before culture. It is well known that many drugs which are widely used in the treatment of acute leukemia are cytotoxic mainly to proliferating cells, so that if quiescent G0 phase cells can be induced to the proliferative stage, the treatment of acute leukemia would become more effective. The present findings showed that a considerable variation was observed among individual patients in the induction of the G0 component to the proliferative stage.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Capability of various cytokines to induce quiescent myeloid leukemia cells to the proliferative stage. In order to investigate the capability of cytokines to induce myeloid leukemia cells from G0 phase to the proliferative stage, blasts from 9 patients with AML and 1 patient with CML-MC were cultured with various cytokines (IL-3, GM-CSF, IL-3 + GM-CSF, G-CSF) for 48 hours or 96 hours in a serum-free culture system. Cells were analyzed by two-color flow cytometry, using PI and the monoclonal antibody Ki-67. The percentage of cells in G0 phase was reduced significantly when the cells were cultured with IL-3 (p < 0.01), GM-CSF (p < 0.01), and IL-3 + GM-CSF (p < 0.01) for 48 hours, as compared with the percentage of cells in G0 phase before culture. Moreover, the percentage of cells in S phase increased significantly when the cells were cultured with IL-3 (p < 0.01), GM-CSF (p < 0.02), and IL-3 + GM-CSF (p < 0.01) for 48 hours, as compared with the percentage of cells in S phase before culture. It is well known that many drugs which are widely used in the treatment of acute leukemia are cytotoxic mainly to proliferating cells, so that if quiescent G0 phase cells can be induced to the proliferative stage, the treatment of acute leukemia would become more effective. The present findings showed that a considerable variation was observed among individual patients in the induction of the G0 component to the proliferative stage.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282064", "title": "CD5 negative IGM rheumatoid factor B cells in B-chronic lymphocytic leukemia and benign mixed cryoglobulinemia.", "content": "IgM-RF B cell precursors are abnormally overrepresented in \"well differentiated\" lymphoid monoclonal proliferations while data on less mature lymphoid malignancies are still awaited. This nevertheless suggests that RF activity plays a role in the transforming process perhaps by inducing constant stimulation of the precursor B cells. Despite the preferential use of similar VH and VL genes with little or no somatic hypermutations in both malignant B-cell CLL and nonmalignant mixed cryoglobulinemia, these proliferations do differ in CD5 membrane expression and in their clinical evolution. One possibility could be that CD5 glycoprotein is lost during maturation of the lymphocyte into a secreting cell as suggested by data on Waldenstr\u00f6m's disease and the LES-CLL and by in vitro studies. Alternatively, CD5 expression could play an additional direct role in malignant transformation as suggested by recent data on the CD5 receptor ligand. Further data on the proliferating cells in both situations as well as on the genetic control of CD5 expression in B cells and its physiology should shed additional light on the mechanisms of B-cell malignancy.", "contents": "CD5 negative IGM rheumatoid factor B cells in B-chronic lymphocytic leukemia and benign mixed cryoglobulinemia. IgM-RF B cell precursors are abnormally overrepresented in \"well differentiated\" lymphoid monoclonal proliferations while data on less mature lymphoid malignancies are still awaited. This nevertheless suggests that RF activity plays a role in the transforming process perhaps by inducing constant stimulation of the precursor B cells. Despite the preferential use of similar VH and VL genes with little or no somatic hypermutations in both malignant B-cell CLL and nonmalignant mixed cryoglobulinemia, these proliferations do differ in CD5 membrane expression and in their clinical evolution. One possibility could be that CD5 glycoprotein is lost during maturation of the lymphocyte into a secreting cell as suggested by data on Waldenstr\u00f6m's disease and the LES-CLL and by in vitro studies. Alternatively, CD5 expression could play an additional direct role in malignant transformation as suggested by recent data on the CD5 receptor ligand. Further data on the proliferating cells in both situations as well as on the genetic control of CD5 expression in B cells and its physiology should shed additional light on the mechanisms of B-cell malignancy."} {"id": "PMID:1282065", "title": "Treatment of BCL-1 murine B-cell leukemia with recombinant cytokines. Comparative analysis of the anti-leukemic potential of interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and their combination.", "content": "Murine BCL-1 B-cell leukemia provides a model of disseminated human B-lineage acute lymphoblastic leukemia (ALL) and non-Hodgkins lymphoma (NHL). This model was used to evaluate and compare the anti-leukemic efficacy of recombinant cytokines rIL-1 beta, rIL-2, rIL-6, rTNF alpha, rG-CSF, rGM-CSF and their combinations. Of these 6 cytokines tested, rG-CSF, rIL-1 beta, rIL-2, and rTNF alpha exerted a marked anti-leukemia/lymphoma activity, as reflected by significantly improved survival of treated mice after inoculation of BCL-1 cells. Notably, no additive or synergistic effects were observed when 2-4 cytokines were used in combination. To our knowledge, this report represents the first comparative analysis of recombinant cytokine treatment regimens in an animal model of disseminated B-lineage ALL/NHL.", "contents": "Treatment of BCL-1 murine B-cell leukemia with recombinant cytokines. Comparative analysis of the anti-leukemic potential of interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF alpha), granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), and their combination. Murine BCL-1 B-cell leukemia provides a model of disseminated human B-lineage acute lymphoblastic leukemia (ALL) and non-Hodgkins lymphoma (NHL). This model was used to evaluate and compare the anti-leukemic efficacy of recombinant cytokines rIL-1 beta, rIL-2, rIL-6, rTNF alpha, rG-CSF, rGM-CSF and their combinations. Of these 6 cytokines tested, rG-CSF, rIL-1 beta, rIL-2, and rTNF alpha exerted a marked anti-leukemia/lymphoma activity, as reflected by significantly improved survival of treated mice after inoculation of BCL-1 cells. Notably, no additive or synergistic effects were observed when 2-4 cytokines were used in combination. To our knowledge, this report represents the first comparative analysis of recombinant cytokine treatment regimens in an animal model of disseminated B-lineage ALL/NHL."} {"id": "PMID:1282066", "title": "A sensitive, quantitative assay for measurement of allele-specific transcripts differing by a single nucleotide.", "content": "We have found that the single nucleotide primer extension assay, a PCR-based assay currently used qualitatively to measure allelic differences in DNA, can be used quantitatively to measure allele-specific transcripts differing by only a single nucleotide. We show that total RNA containing the Pgk-1a transcript can be specifically detected even in a 1000-fold excess of RNA containing the Pgk-1b transcript.", "contents": "A sensitive, quantitative assay for measurement of allele-specific transcripts differing by a single nucleotide. We have found that the single nucleotide primer extension assay, a PCR-based assay currently used qualitatively to measure allelic differences in DNA, can be used quantitatively to measure allele-specific transcripts differing by only a single nucleotide. We show that total RNA containing the Pgk-1a transcript can be specifically detected even in a 1000-fold excess of RNA containing the Pgk-1b transcript."} {"id": "PMID:1282067", "title": "RAPD and other PCR-based analyses of plant genomes using DNA extracted from small leaf disks.", "content": "A nondestructive, early DNA diagnostic system to implement marker-assisted selection in plant breeding programs has been developed. The main components of the system are a rapid and simple DNA microextraction method and fast DNA polymorphism analyses based on site-specific or arbitrary DNA amplification. A small disk (5 mm diameter) is collected from one cotyledon or the first leaf of a young seedling using a common paper punch. Disruption of plant tissues is done by enzymatic digestion of cell walls. This ensures protection from sample-to-sample contamination and uniform DNA yield. DNA isolated from the resulting protoplasts is sufficient to perform a minimum of five and a maximum of 20 PCR reactions/sample. Total DNA, nuclear DNA, and RNA can be analyzed selectively. The system has been tested successfully with eight major crops. Amplification products generated with DNA prepared with this quick procedure are equivalent to those obtained from CsCl-purified DNA. Up to 120 plants can be treated in 2 days and the procedure lends itself to automation. Potential applications in plant breeding will be discussed.", "contents": "RAPD and other PCR-based analyses of plant genomes using DNA extracted from small leaf disks. A nondestructive, early DNA diagnostic system to implement marker-assisted selection in plant breeding programs has been developed. The main components of the system are a rapid and simple DNA microextraction method and fast DNA polymorphism analyses based on site-specific or arbitrary DNA amplification. A small disk (5 mm diameter) is collected from one cotyledon or the first leaf of a young seedling using a common paper punch. Disruption of plant tissues is done by enzymatic digestion of cell walls. This ensures protection from sample-to-sample contamination and uniform DNA yield. DNA isolated from the resulting protoplasts is sufficient to perform a minimum of five and a maximum of 20 PCR reactions/sample. Total DNA, nuclear DNA, and RNA can be analyzed selectively. The system has been tested successfully with eight major crops. Amplification products generated with DNA prepared with this quick procedure are equivalent to those obtained from CsCl-purified DNA. Up to 120 plants can be treated in 2 days and the procedure lends itself to automation. Potential applications in plant breeding will be discussed."} {"id": "PMID:1282070", "title": "Stress response in Drosophila subobscura: DNA-RNA hybrids and transcriptional activity.", "content": "Immunofluorescent techniques have been used in the analysis of DNA-RNA hybrids occurrence and its relationship to transcriptional events on polytene chromosomes of Drosophila subobscura. We have studied the distribution of these hybrids on uninduced/induced chromosomes. Two different indirect immunofluorescence methods for the detection of DNA-RNA hybrids were used. Our data confirm the positive correlation between localization of DNA-RNA hybrids and transcriptional activity by following the B\u00fcsen et al procedure (1982). Using the other protocol, which allows chromosomal DNA-RNA to denature and renature, makes DNA-RNA hybrids detectable not exclusively in active chromosomal regions. Taking B\u00fcsen as method of choice, this technique allowed to localize the exact transcriptional active sites on puffs: hybrid fluorescence was restricted to marginal or central puff areas. Moreover, no correlation between fluorescence and puffs size was found. However, our studies on induced chromosomes indicate that: 1) the 15DE puff, previously described as t-puff, was not really a heat shock puff, since no transcriptional activity was detected; 2) hybrid fluorescence at 2C and 31CD regions was observed. No labelling was found in these loci in the autoradiography data, reported by other authors.", "contents": "Stress response in Drosophila subobscura: DNA-RNA hybrids and transcriptional activity. Immunofluorescent techniques have been used in the analysis of DNA-RNA hybrids occurrence and its relationship to transcriptional events on polytene chromosomes of Drosophila subobscura. We have studied the distribution of these hybrids on uninduced/induced chromosomes. Two different indirect immunofluorescence methods for the detection of DNA-RNA hybrids were used. Our data confirm the positive correlation between localization of DNA-RNA hybrids and transcriptional activity by following the B\u00fcsen et al procedure (1982). Using the other protocol, which allows chromosomal DNA-RNA to denature and renature, makes DNA-RNA hybrids detectable not exclusively in active chromosomal regions. Taking B\u00fcsen as method of choice, this technique allowed to localize the exact transcriptional active sites on puffs: hybrid fluorescence was restricted to marginal or central puff areas. Moreover, no correlation between fluorescence and puffs size was found. However, our studies on induced chromosomes indicate that: 1) the 15DE puff, previously described as t-puff, was not really a heat shock puff, since no transcriptional activity was detected; 2) hybrid fluorescence at 2C and 31CD regions was observed. No labelling was found in these loci in the autoradiography data, reported by other authors."} {"id": "PMID:1282071", "title": "Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774.", "content": "The effect of eicosanoids on the induction of nitric oxide synthase in the murine macrophage cell line J774 has been studied. We found that prostaglandin E2 (PGE2) and iloprost (a stable analogue of prostacyclin) both at nanomolar concentrations inhibited the lipopolysaccharide stimulated induction of NO synthase. In contrast PGF2 alpha, U46619, a stable analogue of thromboxane A2, leukotrienes B4 and C4 had no effect. These data demonstrate that the L-arginine: NO pathway in macrophages may be modulated by prostanoids.", "contents": "Modulation of the induction of nitric oxide synthase by eicosanoids in the murine macrophage cell line J774. The effect of eicosanoids on the induction of nitric oxide synthase in the murine macrophage cell line J774 has been studied. We found that prostaglandin E2 (PGE2) and iloprost (a stable analogue of prostacyclin) both at nanomolar concentrations inhibited the lipopolysaccharide stimulated induction of NO synthase. In contrast PGF2 alpha, U46619, a stable analogue of thromboxane A2, leukotrienes B4 and C4 had no effect. These data demonstrate that the L-arginine: NO pathway in macrophages may be modulated by prostanoids."} {"id": "PMID:1282072", "title": "A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder.", "content": "1. We have estimated potencies of tachykinin receptor agonist and antagonist analogues in order to determine the recognition characteristics of tachykinin receptors mediating phasic contractile responses of the rat isolated urinary bladder in vitro. 2. The NK1-selective synthetic agonists, substance P methyl ester and GR73632, the synthetic NK2-selective agonists [beta-Ala8]-NKA(4-10) and GR64349, and the mammalian tachykinins, neurokinin A and neurokinin B, were assayed relative to substance P and were found to be approximately equipotent. The NK3-selective agonist, senktide, was inactive (10 microM). 3. Potencies of all these agonists were not significantly different (P > 0.05) when experiments were carried out in the presence of the neutral endopeptidase inhibitor, phosphoramidon, and the kininase II inhibitor, enalaprilat (both 1 microM). 4. The NK1-selective antagonist, GR82334, inhibited responses to substance P methyl ester in a competitive manner in the rat urinary bladder and the rat ileum, and also in the guinea-pig ileum. Markedly different pKB estimates were obtained in the rat bladder (6.38) and rat ileum (6.56) compared to the guinea-pig ileum (7.42). GR82334 (3 microM) was inactive against responses of the rat bladder to [beta-Ala8]-NKA(4-10). 5. The NK1-selective antagonist (+/-)-CP-96,345 also inhibited responses of the rat bladder and guinea-pig ileum to substance P methyl ester; however, in the rat bladder at 1 microM, this antagonist reversibly inhibited responses both to the NK2-selective agonist [beta-Ala8]-NKA(4-10) and to the muscarinic agonist carbachol (P < or = 0.01), thus showing evidence of some non-selective depressant actions. 6. The NK2-selective antagonists, MEN10207 and L-659,874, competitively inhibited responses of the rat bladder to the NK2-selective agonist [P-Ala5]-NKA(4-10) giving pKB estimates of 5.75 and 6.68,respectively. Both antagonists (1O microM) were inactive against responses to the NKI-selective agonist substance P methyl ester.7. These results support the proposal of a mixed population of NKI and NK2 receptors mediating contraction of the rat isolated urinary bladder. The NK2 receptor is characterized by a relatively low affinity for the NK2-selective antagonist MEN10207 but a high affinity for L-659,874. The NKImediated responses are inhibited by (+/-)-CP-96,345: this compound however, has non-specific depressant effects in the rat bladder at high concentration (1 microM). In contrast, the NK,-receptor peptide antagonist GR82334, did not have non-specific depressant effects and competitively inhibited NK, responses in the rat bladder and rat ileum with an affinity significantly lower than at the NK,-receptors in the guinea-pigileum.", "contents": "A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder. 1. We have estimated potencies of tachykinin receptor agonist and antagonist analogues in order to determine the recognition characteristics of tachykinin receptors mediating phasic contractile responses of the rat isolated urinary bladder in vitro. 2. The NK1-selective synthetic agonists, substance P methyl ester and GR73632, the synthetic NK2-selective agonists [beta-Ala8]-NKA(4-10) and GR64349, and the mammalian tachykinins, neurokinin A and neurokinin B, were assayed relative to substance P and were found to be approximately equipotent. The NK3-selective agonist, senktide, was inactive (10 microM). 3. Potencies of all these agonists were not significantly different (P > 0.05) when experiments were carried out in the presence of the neutral endopeptidase inhibitor, phosphoramidon, and the kininase II inhibitor, enalaprilat (both 1 microM). 4. The NK1-selective antagonist, GR82334, inhibited responses to substance P methyl ester in a competitive manner in the rat urinary bladder and the rat ileum, and also in the guinea-pig ileum. Markedly different pKB estimates were obtained in the rat bladder (6.38) and rat ileum (6.56) compared to the guinea-pig ileum (7.42). GR82334 (3 microM) was inactive against responses of the rat bladder to [beta-Ala8]-NKA(4-10). 5. The NK1-selective antagonist (+/-)-CP-96,345 also inhibited responses of the rat bladder and guinea-pig ileum to substance P methyl ester; however, in the rat bladder at 1 microM, this antagonist reversibly inhibited responses both to the NK2-selective agonist [beta-Ala8]-NKA(4-10) and to the muscarinic agonist carbachol (P < or = 0.01), thus showing evidence of some non-selective depressant actions. 6. The NK2-selective antagonists, MEN10207 and L-659,874, competitively inhibited responses of the rat bladder to the NK2-selective agonist [P-Ala5]-NKA(4-10) giving pKB estimates of 5.75 and 6.68,respectively. Both antagonists (1O microM) were inactive against responses to the NKI-selective agonist substance P methyl ester.7. These results support the proposal of a mixed population of NKI and NK2 receptors mediating contraction of the rat isolated urinary bladder. The NK2 receptor is characterized by a relatively low affinity for the NK2-selective antagonist MEN10207 but a high affinity for L-659,874. The NKImediated responses are inhibited by (+/-)-CP-96,345: this compound however, has non-specific depressant effects in the rat bladder at high concentration (1 microM). In contrast, the NK,-receptor peptide antagonist GR82334, did not have non-specific depressant effects and competitively inhibited NK, responses in the rat bladder and rat ileum with an affinity significantly lower than at the NK,-receptors in the guinea-pigileum."} {"id": "PMID:1282073", "title": "Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888.", "content": "1. In our search for compounds that inhibit the binding of [3H]-substance P (SP) to guinea-pig lung membranes, the dipeptide SP antagonist, FK888, was developed by chemical modification of the parent compound, (D-Pro4, D-Trp7,9,10, Phe11)SP4-11. 2. In a [3H]-SP binding assay using guinea-pig lung membranes and rat brain cortical synaptic membranes, FK888 displaced [3H]-SP binding with a Ki value of 0.69 +/- 0.13 nM and 0.45 +/- 0.17 microM, respectively, in a competitive manner. 3. FK888 inhibited the contraction of guinea-pig isolated ileum induced by SP in the presence of atropine and indomethacin (a NK1 receptor bioassay) with a pA2 value of 9.29 (8.60-9.98). 4. FK888 inhibited contractions of rat vas deferens by NKA (a NK2 receptor bioassay) and of rat portal vein by NKB (a NK3 receptor bioassay) at concentrations at least 10,000 times greater than that required to inhibit contractions of guinea-pig ileum. 5. FK888 also inhibited SP-induced airway oedema in guinea-pig after both intravenous and oral administration. 6. These data demonstrate that FK888 is a potent and selective NK1 antagonist which is active both in vitro and in vivo.", "contents": "Pharmacological profile of a high affinity dipeptide NK1 receptor antagonist, FK888. 1. In our search for compounds that inhibit the binding of [3H]-substance P (SP) to guinea-pig lung membranes, the dipeptide SP antagonist, FK888, was developed by chemical modification of the parent compound, (D-Pro4, D-Trp7,9,10, Phe11)SP4-11. 2. In a [3H]-SP binding assay using guinea-pig lung membranes and rat brain cortical synaptic membranes, FK888 displaced [3H]-SP binding with a Ki value of 0.69 +/- 0.13 nM and 0.45 +/- 0.17 microM, respectively, in a competitive manner. 3. FK888 inhibited the contraction of guinea-pig isolated ileum induced by SP in the presence of atropine and indomethacin (a NK1 receptor bioassay) with a pA2 value of 9.29 (8.60-9.98). 4. FK888 inhibited contractions of rat vas deferens by NKA (a NK2 receptor bioassay) and of rat portal vein by NKB (a NK3 receptor bioassay) at concentrations at least 10,000 times greater than that required to inhibit contractions of guinea-pig ileum. 5. FK888 also inhibited SP-induced airway oedema in guinea-pig after both intravenous and oral administration. 6. These data demonstrate that FK888 is a potent and selective NK1 antagonist which is active both in vitro and in vivo."} {"id": "PMID:1282074", "title": "Antagonism of kinin effects on epithelial by Hoe 140: apparently competitive and non-competitive interactions.", "content": "1. Hoe-140, a potent kinin receptor antagonist, was investigated for its ability to inhibit the effects of lysylbradykinin (kallidin) on a cultured colonic epithelium, HCA-7 Colony 29, derived from a human adenocarcinoma. 2. Measurements of electrogenic chloride secretion (as short circuit current), and of intracellular Ca2+ (from Fura-2 fluorescence) were used to assess the action of lysylbradykinin in the absence and presence of Hoe 140. 3. From short circuit current data, Hoe 140 appeared to be a competitive antagonist with a Ki value of 5 nM. However, with measurements of intracellular Ca2+ Hoe 140 was apparently a non-competitive antagonist with a Ki of between 4-6 nM. 4. Because of the unexpected finding of non-competitive antagonism, measurements were made with a second antagonist pair, histamine and mepyramine. Mepyramine behaved as a competitive antagonist against responses to histamine with a Ki value of approximately 5 nM when short circuit current measurements were evaluated. However, when intracellular Ca2+ concentration was used as a measure mepyramine, 30 nM, produced a near parallel shift in the response curve, but at 100 nM the maximal response was depressed. 5. The reasons why the apparent type of antagonism depends upon the method of measurement is discussed, bearing in mind that the increase in intracellular Ca2+ is a signal which precedes the increase in short circuit current.", "contents": "Antagonism of kinin effects on epithelial by Hoe 140: apparently competitive and non-competitive interactions. 1. Hoe-140, a potent kinin receptor antagonist, was investigated for its ability to inhibit the effects of lysylbradykinin (kallidin) on a cultured colonic epithelium, HCA-7 Colony 29, derived from a human adenocarcinoma. 2. Measurements of electrogenic chloride secretion (as short circuit current), and of intracellular Ca2+ (from Fura-2 fluorescence) were used to assess the action of lysylbradykinin in the absence and presence of Hoe 140. 3. From short circuit current data, Hoe 140 appeared to be a competitive antagonist with a Ki value of 5 nM. However, with measurements of intracellular Ca2+ Hoe 140 was apparently a non-competitive antagonist with a Ki of between 4-6 nM. 4. Because of the unexpected finding of non-competitive antagonism, measurements were made with a second antagonist pair, histamine and mepyramine. Mepyramine behaved as a competitive antagonist against responses to histamine with a Ki value of approximately 5 nM when short circuit current measurements were evaluated. However, when intracellular Ca2+ concentration was used as a measure mepyramine, 30 nM, produced a near parallel shift in the response curve, but at 100 nM the maximal response was depressed. 5. The reasons why the apparent type of antagonism depends upon the method of measurement is discussed, bearing in mind that the increase in intracellular Ca2+ is a signal which precedes the increase in short circuit current."} {"id": "PMID:1282075", "title": "A possible role of decreased relaxation mediated by beta-adrenoceptors in bladder outlet obstruction by benign prostatic hyperplasia.", "content": "1. To explore mechanisms of urinary obstruction in benign prostatic hyperplasia (BPH), the features of contraction and relaxation in human hyperplastic and non-hyperplastic (control) prostatic tissues were investigated for beta- and alpha 1-adrenoceptors by radioligand binding and in vitro isometric tension experiments. 2. Hyperplastic and control prostatic tissues had a similar number (per mg protein) of prazosin binding sites with similar affinities. Noradrenaline (NA) induced dose-dependent contraction in both tissues. Contraction induced by either exogenous NA or transmural stimulation was inhibited by prazosin in both tissues, indicating that the same contractile mechanisms mediated by alpha 1-adrenoceptors exist in hyperplastic and control tissues. 3. The number of dihydroalprenolol (DHA) binding sites (per mg protein) was less in hyperplastic tissues than in controls, whereas the affinity to the ligand was identical in both tissues. Isoprenaline caused a marked relaxation of the tonic contraction induced by KCl in control tissues, but not in hyperplastic tissues. Propranolol enhanced exogenous NA- or transmural stimulation-induced contraction more in control tissues than in hyperplastic tissues. Both tissues, however, similarly responded to forskolin by relaxation. 4. These results indicate that decreased beta-adrenoceptor-mediated relaxation in hyperplastic prostatic tissues, which is attributable at least in part to the decreased number of beta-adrenoceptors, may play a role in the urinary obstruction of BPH in addition to mechanical compression of the urethra by the enlarged prostate.", "contents": "A possible role of decreased relaxation mediated by beta-adrenoceptors in bladder outlet obstruction by benign prostatic hyperplasia. 1. To explore mechanisms of urinary obstruction in benign prostatic hyperplasia (BPH), the features of contraction and relaxation in human hyperplastic and non-hyperplastic (control) prostatic tissues were investigated for beta- and alpha 1-adrenoceptors by radioligand binding and in vitro isometric tension experiments. 2. Hyperplastic and control prostatic tissues had a similar number (per mg protein) of prazosin binding sites with similar affinities. Noradrenaline (NA) induced dose-dependent contraction in both tissues. Contraction induced by either exogenous NA or transmural stimulation was inhibited by prazosin in both tissues, indicating that the same contractile mechanisms mediated by alpha 1-adrenoceptors exist in hyperplastic and control tissues. 3. The number of dihydroalprenolol (DHA) binding sites (per mg protein) was less in hyperplastic tissues than in controls, whereas the affinity to the ligand was identical in both tissues. Isoprenaline caused a marked relaxation of the tonic contraction induced by KCl in control tissues, but not in hyperplastic tissues. Propranolol enhanced exogenous NA- or transmural stimulation-induced contraction more in control tissues than in hyperplastic tissues. Both tissues, however, similarly responded to forskolin by relaxation. 4. These results indicate that decreased beta-adrenoceptor-mediated relaxation in hyperplastic prostatic tissues, which is attributable at least in part to the decreased number of beta-adrenoceptors, may play a role in the urinary obstruction of BPH in addition to mechanical compression of the urethra by the enlarged prostate."} {"id": "PMID:1282076", "title": "Nitric oxide synthase in ferret brain: localization and characterization.", "content": "1. In the present study, we have investigated the distribution of nitric oxide synthase in the ferret brain. Nitric oxide synthase was determined biochemically and immunochemically. 2. In the rat brain, the highest nitric oxide synthase activity has been detected in the cerebellum. However, in the ferret brain, the highest activity was found in the striatum and the lowest in the cerebellum and cerebral cortex. The enzymatic activity was localized predominantly in the cytosolic fractions, it was dependent on NADPH and Ca2+, and inhibited by NG-nitro-L-arginine or NG-methyl-L-arginine. 3. Western blot analysis revealed that all regions of the ferret brain contained a 160 kD protein crossreacting with an antibody to nitric oxide synthase purified from the rat cerebellum, and the levels of relative intensity of staining by the antibody correlated with the distribution of nitric oxide synthase activity. 4. These results indicate that the ferret brain contains a nitric oxide synthase similar to the rat brain, but the distribution of enzymatic activity in the ferret brain differs markedly from the rat brain.", "contents": "Nitric oxide synthase in ferret brain: localization and characterization. 1. In the present study, we have investigated the distribution of nitric oxide synthase in the ferret brain. Nitric oxide synthase was determined biochemically and immunochemically. 2. In the rat brain, the highest nitric oxide synthase activity has been detected in the cerebellum. However, in the ferret brain, the highest activity was found in the striatum and the lowest in the cerebellum and cerebral cortex. The enzymatic activity was localized predominantly in the cytosolic fractions, it was dependent on NADPH and Ca2+, and inhibited by NG-nitro-L-arginine or NG-methyl-L-arginine. 3. Western blot analysis revealed that all regions of the ferret brain contained a 160 kD protein crossreacting with an antibody to nitric oxide synthase purified from the rat cerebellum, and the levels of relative intensity of staining by the antibody correlated with the distribution of nitric oxide synthase activity. 4. These results indicate that the ferret brain contains a nitric oxide synthase similar to the rat brain, but the distribution of enzymatic activity in the ferret brain differs markedly from the rat brain."} {"id": "PMID:1282077", "title": "Effect of substance P on circadian rhythms of firing activity and the 2-deoxyglucose uptake in the rat suprachiasmatic nucleus in vitro.", "content": "The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. Although substance P (SP) fibers from retina are found to terminate the SCN, the physiological role of this peptide is uncertain. The 2-deoxyglucose (2-DG) uptake and firing activity in the SCN show a robust circadian change. SP causes an increase in 2-DG uptake by SCN during the subjective night but not during subjective day. SP-induced increase in 2-DG uptake is blocked by co-treatment with the SP receptor antagonist, spantide. Treatment with SP produces phase shifts of circadian rhythm in spontaneous neural activity in SCN neurons with a phase-response curve that is similar to the effect of light pulses to animals under constant darkness. SP-induced phase change is also blocked by pretreatment with spantide. SP-induced increase in 2-DG uptake and phase changes in firing activity occur only during subjective night, at circadian times when photic phase shifting of activity occurs. The present results suggest that SP may be an important transmitter for conveying environmental light-dark information from retina to the SCN.", "contents": "Effect of substance P on circadian rhythms of firing activity and the 2-deoxyglucose uptake in the rat suprachiasmatic nucleus in vitro. The suprachiasmatic nuclei (SCN) have been identified as a pacemaker for many circadian rhythms in mammals. Although substance P (SP) fibers from retina are found to terminate the SCN, the physiological role of this peptide is uncertain. The 2-deoxyglucose (2-DG) uptake and firing activity in the SCN show a robust circadian change. SP causes an increase in 2-DG uptake by SCN during the subjective night but not during subjective day. SP-induced increase in 2-DG uptake is blocked by co-treatment with the SP receptor antagonist, spantide. Treatment with SP produces phase shifts of circadian rhythm in spontaneous neural activity in SCN neurons with a phase-response curve that is similar to the effect of light pulses to animals under constant darkness. SP-induced phase change is also blocked by pretreatment with spantide. SP-induced increase in 2-DG uptake and phase changes in firing activity occur only during subjective night, at circadian times when photic phase shifting of activity occurs. The present results suggest that SP may be an important transmitter for conveying environmental light-dark information from retina to the SCN."} {"id": "PMID:1282078", "title": "TRH regulation of tracheal tension through vagal preganglionic motoneurons.", "content": "TRH-immunoreactive nerve terminals innervate the ambiguous nucleus in the rabbit. Vagal preganglionic motoneurons that innervate the trachea, were revealed by HRP histochemistry in the rostral part of the ambiguous nucleus and the dorsal motor nucleus of the vagus. HRP histochemistry plus TRH immunocytochemistry revealed that TRH-immunoreactive axon terminals synapsed on ambiguous nucleus neurons retrogradely labeled by HRP injection into tracheal smooth muscle and the superior laryngeal nerve. Microinjection of 50 ng TRH into the rostral ambiguous nucleus caused slight dilation followed by constriction, which was inhibited by atropine and vagotomy. Results show that central TRH-containing neurons regulate tracheal tension through synapses on vagal preganglionic motoneurons that innervate tracheal smooth muscle.", "contents": "TRH regulation of tracheal tension through vagal preganglionic motoneurons. TRH-immunoreactive nerve terminals innervate the ambiguous nucleus in the rabbit. Vagal preganglionic motoneurons that innervate the trachea, were revealed by HRP histochemistry in the rostral part of the ambiguous nucleus and the dorsal motor nucleus of the vagus. HRP histochemistry plus TRH immunocytochemistry revealed that TRH-immunoreactive axon terminals synapsed on ambiguous nucleus neurons retrogradely labeled by HRP injection into tracheal smooth muscle and the superior laryngeal nerve. Microinjection of 50 ng TRH into the rostral ambiguous nucleus caused slight dilation followed by constriction, which was inhibited by atropine and vagotomy. Results show that central TRH-containing neurons regulate tracheal tension through synapses on vagal preganglionic motoneurons that innervate tracheal smooth muscle."} {"id": "PMID:1282079", "title": "Time-dependent regenerative influence of predegenerated nerve grafts on hippocampus.", "content": "Our previous studies have revealed that the predegeneration facilitated the neurite outgrowth from hippocampus following the peripheral nerve grafts implantation. The aim of the present work is to find whether the stimulative power of peripheral nerve grafts depends on the time lapse after the transection. Autologous predegenerated distal stumps of the rat sciatic nerves were implanted into the hippocampus on the 7th, 14th, 28th, and 35th day following the transection. Six weeks later, horseradish peroxidase conjugated with fluorescein isothiocyanate was injected into the graft and frozen sections of brains were made. Fluorescence microscope examination has shown that FITC-HRP labeled cells were present among the hippocampal neurons in all the brains under examination, excluding these grafted with 14-day predegenerated peripheral nerves. The FITC-HRP labeled neurons were particularly numerous when the 7- and 35-day-old predegenerated stumps were used as grafts.", "contents": "Time-dependent regenerative influence of predegenerated nerve grafts on hippocampus. Our previous studies have revealed that the predegeneration facilitated the neurite outgrowth from hippocampus following the peripheral nerve grafts implantation. The aim of the present work is to find whether the stimulative power of peripheral nerve grafts depends on the time lapse after the transection. Autologous predegenerated distal stumps of the rat sciatic nerves were implanted into the hippocampus on the 7th, 14th, 28th, and 35th day following the transection. Six weeks later, horseradish peroxidase conjugated with fluorescein isothiocyanate was injected into the graft and frozen sections of brains were made. Fluorescence microscope examination has shown that FITC-HRP labeled cells were present among the hippocampal neurons in all the brains under examination, excluding these grafted with 14-day predegenerated peripheral nerves. The FITC-HRP labeled neurons were particularly numerous when the 7- and 35-day-old predegenerated stumps were used as grafts."} {"id": "PMID:1282080", "title": "Sources of noradrenergic afferents to the hypoglossal nucleus in the rat.", "content": "The sources of noradrenergic (NA) innervation to the hypoglossal nucleus (nXII) in the rat were investigated with double-labeling histochemical/immunocytochemical and lesion/degeneration techniques. Following injection of wheat germ-agglutinin conjugated to horseradish peroxidase into nXII, brain stem sections were reacted with tetramethylbenzidine, stabilized, and incubated in antiserum to tyrosine hydroxylase (TH). Double-labeled neurons were observed in three pontine sites bilaterally, although mainly ipsilaterally, that included the nucleus subceruleus (nSC; 68.75%) and the A7 (21.09%) and A5 (10.15%) cell groups. Confirmation of the above results and identification of the course taken by descending NA-nXII projections was accomplished by lesioning the rostral pons, the nSC, or the medullary catecholamine bundle (MB), the suspected route by which NA afferents reach nXII. Quantitative estimates of the reduction of TH immunoreactivity on the lesioned compared to nonlesioned side of nXII were made densitometrically. In each case, TH immunostaining was significantly decreased (75%) in the ipsilateral caudoventromedial district of nXII, the predominant target area of NA input. The results from this study establish that multiple NA sources in the pons project to nXII in the rat, the majority of NA-nXII afferents are derived from the nSC, and descending NA-nXII projections course in the MB. These data are discussed relative to tongue control.", "contents": "Sources of noradrenergic afferents to the hypoglossal nucleus in the rat. The sources of noradrenergic (NA) innervation to the hypoglossal nucleus (nXII) in the rat were investigated with double-labeling histochemical/immunocytochemical and lesion/degeneration techniques. Following injection of wheat germ-agglutinin conjugated to horseradish peroxidase into nXII, brain stem sections were reacted with tetramethylbenzidine, stabilized, and incubated in antiserum to tyrosine hydroxylase (TH). Double-labeled neurons were observed in three pontine sites bilaterally, although mainly ipsilaterally, that included the nucleus subceruleus (nSC; 68.75%) and the A7 (21.09%) and A5 (10.15%) cell groups. Confirmation of the above results and identification of the course taken by descending NA-nXII projections was accomplished by lesioning the rostral pons, the nSC, or the medullary catecholamine bundle (MB), the suspected route by which NA afferents reach nXII. Quantitative estimates of the reduction of TH immunoreactivity on the lesioned compared to nonlesioned side of nXII were made densitometrically. In each case, TH immunostaining was significantly decreased (75%) in the ipsilateral caudoventromedial district of nXII, the predominant target area of NA input. The results from this study establish that multiple NA sources in the pons project to nXII in the rat, the majority of NA-nXII afferents are derived from the nSC, and descending NA-nXII projections course in the MB. These data are discussed relative to tongue control."} {"id": "PMID:1282082", "title": "Whole-cell chloride conductances in cultured brushed human nasal epithelial cells.", "content": "Human airway epithelial cells were obtained by nasal brushing, thus avoiding the use of proteolytic enzymes for cell isolation. Whole-cell Cl- conductances were studied in these cells by means of the patch-clamp technique. During whole-cell recordings, cell swelling activated a Cl- conductance that was blocked by indanyloxyacetic acid (48 +/- 10% inhibition at 50 microM). The swelling-induced current outwardly rectified and showed inactivation at depolarizing voltages (> or = +60 mV) and activation at hyperpolarizing voltages (< or = -30 mV). The voltage sensitivity of current activation was approximately twice that of inactivation. Another Cl- current with different kinetics was observed when nonswollen airway cells were stimulated with ionomycin (2 microM) in the presence of 1 mM Ca2+. The Ca(2+)-induced current exhibited activation during depolarizing voltage steps (> or = +40 mV) and inactivation during hyperpolarizing voltage steps (< or = -40 mV). In contrast to the swelling-induced current, the activation of Ca(2+)-induced current was less sensitive to voltage compared with its inactivation. Tail current analysis suggested that Cl- channels having a linear current-voltage relation mediate the response to Ca2+. This study indicates that brushed human nasal epithelial cells possess Cl- conductances that are regulated by cell swelling and Ca2+ and that they represent a useful in vitro model for studying ion transport in epithelia.", "contents": "Whole-cell chloride conductances in cultured brushed human nasal epithelial cells. Human airway epithelial cells were obtained by nasal brushing, thus avoiding the use of proteolytic enzymes for cell isolation. Whole-cell Cl- conductances were studied in these cells by means of the patch-clamp technique. During whole-cell recordings, cell swelling activated a Cl- conductance that was blocked by indanyloxyacetic acid (48 +/- 10% inhibition at 50 microM). The swelling-induced current outwardly rectified and showed inactivation at depolarizing voltages (> or = +60 mV) and activation at hyperpolarizing voltages (< or = -30 mV). The voltage sensitivity of current activation was approximately twice that of inactivation. Another Cl- current with different kinetics was observed when nonswollen airway cells were stimulated with ionomycin (2 microM) in the presence of 1 mM Ca2+. The Ca(2+)-induced current exhibited activation during depolarizing voltage steps (> or = +40 mV) and inactivation during hyperpolarizing voltage steps (< or = -40 mV). In contrast to the swelling-induced current, the activation of Ca(2+)-induced current was less sensitive to voltage compared with its inactivation. Tail current analysis suggested that Cl- channels having a linear current-voltage relation mediate the response to Ca2+. This study indicates that brushed human nasal epithelial cells possess Cl- conductances that are regulated by cell swelling and Ca2+ and that they represent a useful in vitro model for studying ion transport in epithelia."} {"id": "PMID:1282083", "title": "Specific endothelin binding sites in renal medullary collecting duct cells: lack of interaction with ANP binding and cGMP signalling.", "content": "The diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 compared with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10(-6) M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 +/- 10.3 fmol/10(6) cells) and high affinity (Kd = 69.8 +/- 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 +/- 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10(-7) M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10(-7) M ANP), nor basal levels of cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Specific endothelin binding sites in renal medullary collecting duct cells: lack of interaction with ANP binding and cGMP signalling. The diverse biological actions of endothelins (ET) appear to be mediated by specific cell-surface receptors. Autoradiography and membrane binding studies have shown abundant ET binding sites in the kidney. However, their expression in specific types of renal cells is unclear. We studied the binding of 125I-labelled endothelin-1 in freshly isolated cell suspensions from canine inner medullary collecting duct. Competition binding experiments revealed the presence of specific high-affinity binding sites: unlabelled ET-1 and ET-2 compared with the radioligand with an IC50 of 135 and 83 pM, respectively, while the IC50 of ET-3 and big ET-1 were 2 and 4 orders of magnitude higher, indicating the presence of ETA-type receptor. Angiotensin II, vasopressin, and atrial natriuretic peptide (ANP) did not compete for ET binding even at a concentration of 10(-6) M. Saturation binding experiments showed a single class of binding sites of high density (Bmax = 56.7 +/- 10.3 fmol/10(6) cells) and high affinity (Kd = 69.8 +/- 10 pM). In contrast, ANP receptors in the same cell preparations appeared as two classes of binding sites with widely different affinity and density. The high-affinity ANP site (Kd = 311 +/- 48 pM) was compatible with ANP-B (guanylate cyclase-coupled) receptor. ET-1 did not compete for this receptor. ET-1 (10(-7) M) did not alter ANP-induced cGMP generation in these cells (3.8-fold increase at 10(-7) M ANP), nor basal levels of cGMP.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282081", "title": "Retroperitoneal Castleman's tumors of hyaline vascular type: imaging study. Case report.", "content": "We report two retroperitoneal Castleman's tumors (giant lymph node hyperplasia) of hyaline vascular type. One was a large tumor situated in the pararenal region, the other was located in the pancreas head. On computed tomography (CT), both tumors were solid and moderately enhanced after administration of contrast material. On angiography, both tumors were hypervascular with dilated feeding arteries, and showed capillary blush. In an appropriate clinical setting, a retroperitoneal tumor showing these findings should include Castleman's tumor in the differential diagnosis.", "contents": "Retroperitoneal Castleman's tumors of hyaline vascular type: imaging study. Case report. We report two retroperitoneal Castleman's tumors (giant lymph node hyperplasia) of hyaline vascular type. One was a large tumor situated in the pararenal region, the other was located in the pancreas head. On computed tomography (CT), both tumors were solid and moderately enhanced after administration of contrast material. On angiography, both tumors were hypervascular with dilated feeding arteries, and showed capillary blush. In an appropriate clinical setting, a retroperitoneal tumor showing these findings should include Castleman's tumor in the differential diagnosis."} {"id": "PMID:1282084", "title": "Mouse U14 snRNA is a processed intron of the cognate hsc70 heat shock pre-messenger RNA.", "content": "U14 snRNA is a small nucleolar RNA species essential for eukaryotic pre-rRNA processing. We have previously shown that the mouse U14 snRNA genes are positioned within introns 5, 6, and 8 on the coding strand of the constitutively expressed cognate hsc70 heat shock gene. This genomic organization suggested the possibility that U14 snRNAs are transcribed as part of the hsc70 pre-mRNA and then excised from the intron to yield mature U14 snRNA species. To test this hypothesis directly, we have microinjected Xenopus oocytes with hsc70 pre-mRNA transcripts possessing intron 5 and the encoded U14 snRNA sequence. Processing results demonstrate that, in addition to the splicing of upstream and downstream exons, a mature 87 nt U14 snRNA is excised from the intron. Accurate excision of U14 snRNA from hsc70 intron 5 can occur in the absence of splicing. These results demonstrate a biosynthetic pathway for an snRNA species and provide a novel example of a eukaryotic pre-mRNA intron that is processed to produce a stable, biologically functional RNA species.", "contents": "Mouse U14 snRNA is a processed intron of the cognate hsc70 heat shock pre-messenger RNA. U14 snRNA is a small nucleolar RNA species essential for eukaryotic pre-rRNA processing. We have previously shown that the mouse U14 snRNA genes are positioned within introns 5, 6, and 8 on the coding strand of the constitutively expressed cognate hsc70 heat shock gene. This genomic organization suggested the possibility that U14 snRNAs are transcribed as part of the hsc70 pre-mRNA and then excised from the intron to yield mature U14 snRNA species. To test this hypothesis directly, we have microinjected Xenopus oocytes with hsc70 pre-mRNA transcripts possessing intron 5 and the encoded U14 snRNA sequence. Processing results demonstrate that, in addition to the splicing of upstream and downstream exons, a mature 87 nt U14 snRNA is excised from the intron. Accurate excision of U14 snRNA from hsc70 intron 5 can occur in the absence of splicing. These results demonstrate a biosynthetic pathway for an snRNA species and provide a novel example of a eukaryotic pre-mRNA intron that is processed to produce a stable, biologically functional RNA species."} {"id": "PMID:1282085", "title": "Differentiation and dedifferentiation of the human monocytic leukemia cell line, U937.", "content": "U937 cells were differentiated into macrophages after being treated with 12-o-tetradecanoyl-phorbol-13-acetate (TPA) for the first two days and dedifferentiated with daily medium renewal for 10 days. Cell proliferation slowed down and the number of cells reached the maximum level on day 2. By day 4, all of the cells had spread and attached firmly to the culture dish, and more than 90% of the cells expressed the Fc-receptor and produced superoxide anion. From there on, the number of adherent, living cells decreased gradually to about half the initial count. Most of the cells eliminated from the culture by cell death were in the S phase at the time of TPA treatment. After day 8, the number of cells expressing macrophage-specific phenotypes gradually decreased, cell adhesion was weakened, and at the same time, DNA synthesis was initiated anew. The cells became round and began to proliferate as floating cells on days 9 to 10, and thereafter they became sensitive to the second round of TPA treatment. On the basis of all the results taken together, it is suggested that fully differentiated U937 cells were dedifferentiated after being cultured with frequent medium renewal.", "contents": "Differentiation and dedifferentiation of the human monocytic leukemia cell line, U937. U937 cells were differentiated into macrophages after being treated with 12-o-tetradecanoyl-phorbol-13-acetate (TPA) for the first two days and dedifferentiated with daily medium renewal for 10 days. Cell proliferation slowed down and the number of cells reached the maximum level on day 2. By day 4, all of the cells had spread and attached firmly to the culture dish, and more than 90% of the cells expressed the Fc-receptor and produced superoxide anion. From there on, the number of adherent, living cells decreased gradually to about half the initial count. Most of the cells eliminated from the culture by cell death were in the S phase at the time of TPA treatment. After day 8, the number of cells expressing macrophage-specific phenotypes gradually decreased, cell adhesion was weakened, and at the same time, DNA synthesis was initiated anew. The cells became round and began to proliferate as floating cells on days 9 to 10, and thereafter they became sensitive to the second round of TPA treatment. On the basis of all the results taken together, it is suggested that fully differentiated U937 cells were dedifferentiated after being cultured with frequent medium renewal."} {"id": "PMID:1282087", "title": "Structure and expression of the rice mitochondrial apocytochrome b gene (cob-1) and pseudogene (cob-2).", "content": "Rice mitochondrial DNA contains an intact copy and a pseudogene copy of a apocytochrome b gene (cob-1 and cob-2, respectively). Using primer extension and capping analyses, the transcriptional start site has been mapped; an 11-base motif at the transcription start site closely matches the consensus promoter motifs proposed for maize, wheat and soybean mitochondrial genes. Although both copies are identical in the 5' upstream region and through most of the coding region, only cob-1-specific mRNA is detected on RNA gel-blots. Run-on transcription analysis indicates, however, that both cob-1 and cob-2 mRNAs are synthesized in vivo but less cob-2 is accumulated. At its mapped 3' terminus the cob-1 transcript possesses a sequence that could fold into a double stem-loop structure. The possible roles of a double stem-loop structure in mitochondrial gene expression are discussed.", "contents": "Structure and expression of the rice mitochondrial apocytochrome b gene (cob-1) and pseudogene (cob-2). Rice mitochondrial DNA contains an intact copy and a pseudogene copy of a apocytochrome b gene (cob-1 and cob-2, respectively). Using primer extension and capping analyses, the transcriptional start site has been mapped; an 11-base motif at the transcription start site closely matches the consensus promoter motifs proposed for maize, wheat and soybean mitochondrial genes. Although both copies are identical in the 5' upstream region and through most of the coding region, only cob-1-specific mRNA is detected on RNA gel-blots. Run-on transcription analysis indicates, however, that both cob-1 and cob-2 mRNAs are synthesized in vivo but less cob-2 is accumulated. At its mapped 3' terminus the cob-1 transcript possesses a sequence that could fold into a double stem-loop structure. The possible roles of a double stem-loop structure in mitochondrial gene expression are discussed."} {"id": "PMID:1282088", "title": "Both open reading frames of the linear plasmid pMC3-2 from the ascomycete Morchella conica are transcribed in vivo.", "content": "Mitochondrial RNA was isolated from the morel strain Morchella conica 3 harbouring the linear plasmid pMC3-2 and subjected to gel electrophoresis followed by a Northern analysis using cloned fragments of the plasmid pMC3-2 as probes. Hybridization was obtained only with central parts of pMC3-2 and specific bands of mtRNA. The hybridization bands (2.8 kb and 1.0 kb) correspond in size to the length of the two ORFs of pMC3-2 which were deduced from nucleotide-sequence data. Thus, both ORFs, one encoding a DNA polymerase and the other a yet unknown protein, are transcribed in the mitochondria of the plasmid-bearing Morchella conica strain.", "contents": "Both open reading frames of the linear plasmid pMC3-2 from the ascomycete Morchella conica are transcribed in vivo. Mitochondrial RNA was isolated from the morel strain Morchella conica 3 harbouring the linear plasmid pMC3-2 and subjected to gel electrophoresis followed by a Northern analysis using cloned fragments of the plasmid pMC3-2 as probes. Hybridization was obtained only with central parts of pMC3-2 and specific bands of mtRNA. The hybridization bands (2.8 kb and 1.0 kb) correspond in size to the length of the two ORFs of pMC3-2 which were deduced from nucleotide-sequence data. Thus, both ORFs, one encoding a DNA polymerase and the other a yet unknown protein, are transcribed in the mitochondria of the plasmid-bearing Morchella conica strain."} {"id": "PMID:1282089", "title": "[The role of oxygen radicals in bleomycin-induced pulmonary fibrosis].", "content": "A model of pulmonary fibrosis in rat has been developed using intratracheal administration of bleomycin (BLM) A5 (5mg/kg). Histopathologic features and total lung collagen were studied. We found that type I pneumocytes detached, basement membrane denuded and endothelia edema were the earliest changes in BLM induced pulmonary fibrosis. Serum MDA (an index of lipid peroxidation) level in rats receiving intratracheal bleomycin were increased at earlier time after bleomycin administration. Meanwhile, MDA level in the lung homogenate was elevated too. Our results indicated that the injured type I pneumocytes and endothelia caused by oxygen radicles are the fundamental damages in bleomycin-induced pulmonary fibrosis.", "contents": "[The role of oxygen radicals in bleomycin-induced pulmonary fibrosis]. A model of pulmonary fibrosis in rat has been developed using intratracheal administration of bleomycin (BLM) A5 (5mg/kg). Histopathologic features and total lung collagen were studied. We found that type I pneumocytes detached, basement membrane denuded and endothelia edema were the earliest changes in BLM induced pulmonary fibrosis. Serum MDA (an index of lipid peroxidation) level in rats receiving intratracheal bleomycin were increased at earlier time after bleomycin administration. Meanwhile, MDA level in the lung homogenate was elevated too. Our results indicated that the injured type I pneumocytes and endothelia caused by oxygen radicles are the fundamental damages in bleomycin-induced pulmonary fibrosis."} {"id": "PMID:1282090", "title": "[Immunohistochemical and quantitative morphological studies of duct-acinar dysplasia in the prostate].", "content": "A series of 56 cases of prostatic adenocarcinoma and 48 cases of benign prostate hyperplasia were studied with histochemical, immunohistochemical methods and Feulgen-Image Analysis Technique. Duct-acinar dysplasia (DAD) was found in 81.8% of the prostate adenocarcinoma cases collected, but only in 47.9% of the benign hyperplasia cases. The frequency and extent of disruption of basal cell layer increased coincidently with the progressive increase of DAD grading. Intraluminal acid mucin and metachromasia stained with toluidine blue around the acini were identified in DAD. Immunohistochemical staining for prostatic acid phosphatase, cytokeratin, vimentin and UEA-1 receptor changed in DAD cells. The nuclear areas, DNA content and ploidy, mean numbers of AgNOR in DAD cells were higher than those in benign hyperplasia of the prostates and lower than those in adenocarcinomas, which indicates the possession of premalignant behavior of prostatic carcinoma.", "contents": "[Immunohistochemical and quantitative morphological studies of duct-acinar dysplasia in the prostate]. A series of 56 cases of prostatic adenocarcinoma and 48 cases of benign prostate hyperplasia were studied with histochemical, immunohistochemical methods and Feulgen-Image Analysis Technique. Duct-acinar dysplasia (DAD) was found in 81.8% of the prostate adenocarcinoma cases collected, but only in 47.9% of the benign hyperplasia cases. The frequency and extent of disruption of basal cell layer increased coincidently with the progressive increase of DAD grading. Intraluminal acid mucin and metachromasia stained with toluidine blue around the acini were identified in DAD. Immunohistochemical staining for prostatic acid phosphatase, cytokeratin, vimentin and UEA-1 receptor changed in DAD cells. The nuclear areas, DNA content and ploidy, mean numbers of AgNOR in DAD cells were higher than those in benign hyperplasia of the prostates and lower than those in adenocarcinomas, which indicates the possession of premalignant behavior of prostatic carcinoma."} {"id": "PMID:1282091", "title": "[The ultrastructural and immunohistochemical observations of anaplastic meningioma].", "content": "Eighteen cases of anaplastic meningioma were studied by LM, EM and immunohistochemistry for vimentin, EMA, keratin, GFAP and S-100. Microscopically, there were four histologic types, i.e. fibrosarcoma-like, angiosarcoma-like, polymorphic giant cell sarcoma-like and angiopapillary structure. By EM, four kinds of cells: undifferentiated cell, intermediate transitional cell, spindle-shaped cell, and giant cell, were found and variant transitions from undifferentiated or poorly, differentiated to meningioma cells were observed. Their ultrastructures and immunohistochemical features are similar to those of malignant mesothelioma. Since these two kinds of neoplasm showed both mesenchymal and epithelial cells in the features, the authors consider that their histogenesis may also be similar.", "contents": "[The ultrastructural and immunohistochemical observations of anaplastic meningioma]. Eighteen cases of anaplastic meningioma were studied by LM, EM and immunohistochemistry for vimentin, EMA, keratin, GFAP and S-100. Microscopically, there were four histologic types, i.e. fibrosarcoma-like, angiosarcoma-like, polymorphic giant cell sarcoma-like and angiopapillary structure. By EM, four kinds of cells: undifferentiated cell, intermediate transitional cell, spindle-shaped cell, and giant cell, were found and variant transitions from undifferentiated or poorly, differentiated to meningioma cells were observed. Their ultrastructures and immunohistochemical features are similar to those of malignant mesothelioma. Since these two kinds of neoplasm showed both mesenchymal and epithelial cells in the features, the authors consider that their histogenesis may also be similar."} {"id": "PMID:1282092", "title": "[Morphological study of reticulo-epithelial cells in atrophic thymus].", "content": "Anti-keratin and PAP immunohistochemical reaction on atrophic thymus collected from 97 autopsies were studied. Among them, 61 cases belonged to the severs type, whose reticulo-epithelial cells were falling into 4 types: the normal type, the centrally focused type, the diffused type and the depletive type. In 37 out of 61 cases, the reticulo-epithelial cells showed proliferation, especially in the medullary zone. All of 7 cases known as physiological involutional thymus turned to depletive type. 11 cases of atrophic thymus studied by scanning electron microscopy had been classified morphologically into 3 patterns, namely: the reticular form, the honey-combed form and the depletive form respectively.", "contents": "[Morphological study of reticulo-epithelial cells in atrophic thymus]. Anti-keratin and PAP immunohistochemical reaction on atrophic thymus collected from 97 autopsies were studied. Among them, 61 cases belonged to the severs type, whose reticulo-epithelial cells were falling into 4 types: the normal type, the centrally focused type, the diffused type and the depletive type. In 37 out of 61 cases, the reticulo-epithelial cells showed proliferation, especially in the medullary zone. All of 7 cases known as physiological involutional thymus turned to depletive type. 11 cases of atrophic thymus studied by scanning electron microscopy had been classified morphologically into 3 patterns, namely: the reticular form, the honey-combed form and the depletive form respectively."} {"id": "PMID:1282093", "title": "[Experimental study of the effect of IH764-3, a potent component isolated from salviae milltiorrhize, against pulmonary fibrosis].", "content": "IH764-3, an effective component isolated from Salvae milliorrhize (a component of traditional Chinese medicine) was used against pulmonary fibrosis in this study. The results indicated that in the treated group, lung coefficient, surfactant, hydroxyproline content and FGF activity were significantly lower than those in the model group. Electron microscopic observation confirmed that the pulmonary ultrastructure was improved remarkably in the treated group: the proliferation of collagen-forming cells and infiltration of inflammatory cells, collagen and elastic fibers were obviously less. All the results demonstrated that IH764-3 has prophylactic and therapeutic effects on the development of pneumonitis and pulmonary fibrosis.", "contents": "[Experimental study of the effect of IH764-3, a potent component isolated from salviae milltiorrhize, against pulmonary fibrosis]. IH764-3, an effective component isolated from Salvae milliorrhize (a component of traditional Chinese medicine) was used against pulmonary fibrosis in this study. The results indicated that in the treated group, lung coefficient, surfactant, hydroxyproline content and FGF activity were significantly lower than those in the model group. Electron microscopic observation confirmed that the pulmonary ultrastructure was improved remarkably in the treated group: the proliferation of collagen-forming cells and infiltration of inflammatory cells, collagen and elastic fibers were obviously less. All the results demonstrated that IH764-3 has prophylactic and therapeutic effects on the development of pneumonitis and pulmonary fibrosis."} {"id": "PMID:1282094", "title": "[Protective effect of 764-3 on experimental lung fibrosis in rats].", "content": "Bleomycin was given to rats via a single intratracheal injection to investigate the development of lung inflammation and fibrosis. Increases in lung index and lung histamine content after 7 and 21 days and an increase of serum MDA content after 21 days were found. But there was no obvious change in lung hydroxyproline content. The results indicated that the acute and subacute inflammatory phases were induced by bleomycin over this period. Lung hydroxyproline content significantly increased after 60 days, demonstrating the onset of fibrosis. 764-3 treatment could obviously attenuate the changes in the above mentioned parameters, suggesting that 764-3 can prevent the lung inflammation and ensuing fibrosis caused by bleomycin. Besides direct antiinflammatory effects in the early phase, direct and indirect antifibrotic actions might also be part of the 764-3 protective effect.", "contents": "[Protective effect of 764-3 on experimental lung fibrosis in rats]. Bleomycin was given to rats via a single intratracheal injection to investigate the development of lung inflammation and fibrosis. Increases in lung index and lung histamine content after 7 and 21 days and an increase of serum MDA content after 21 days were found. But there was no obvious change in lung hydroxyproline content. The results indicated that the acute and subacute inflammatory phases were induced by bleomycin over this period. Lung hydroxyproline content significantly increased after 60 days, demonstrating the onset of fibrosis. 764-3 treatment could obviously attenuate the changes in the above mentioned parameters, suggesting that 764-3 can prevent the lung inflammation and ensuing fibrosis caused by bleomycin. Besides direct antiinflammatory effects in the early phase, direct and indirect antifibrotic actions might also be part of the 764-3 protective effect."} {"id": "PMID:1282095", "title": "Colloidal gold ultraimmunocytochemical localization of DNA and RNA adducts in rat hepatocytes.", "content": "The localization of DNA and RNA adducts was studied at the ultrastructural level using antibodies directed against O6-methylguanine (O6-metG) and the protein A-gold technique. Primary rat hepatocyte cultures were exposed for 2 h to 5 mM N-nitrosodimethylamine (NDMA). In NDMA-treated cells, the O6-metG-induced immunoreactive sites do not appear at random but seem to be concentrated in the nucleus, and in the cytoplasm, in areas rich in rough endoplasmic reticulum (RER) elements. Mitochondria were not significantly labelled. Untreated control preparations showed no specific immunogold labelling. After RNase digestion of ultrathin sections obtained from cells exposed to NDMA and subsequent immunogold labelling, most of the immunolabelling in the cytoplasm had disappeared, and that over the nucleus had only been slightly reduced, as compared to undigested specimens from NDMA-treated cultures. After similar digestion with DNase, a strong reduction of the labelling of the nucleus was observed, but labelling of the cytoplasm was practically unaffected by this enzymatic treatment, as compared to what was observed in undigested preparations of NDMA-treated hepatocytes. The results provide evidence of preferential formation of O6-metG at the DNA and RNA levels, in the nucleus and cytoplasm RER, respectively. Furthermore, this study demonstrates the applicability of the high-resolution protein A-gold technique for ultrastructural detection of nucleic acid adducts in NDMA-treated hepatocytes using affinity-purified anti-O6-metG polyclonal antibodies.", "contents": "Colloidal gold ultraimmunocytochemical localization of DNA and RNA adducts in rat hepatocytes. The localization of DNA and RNA adducts was studied at the ultrastructural level using antibodies directed against O6-methylguanine (O6-metG) and the protein A-gold technique. Primary rat hepatocyte cultures were exposed for 2 h to 5 mM N-nitrosodimethylamine (NDMA). In NDMA-treated cells, the O6-metG-induced immunoreactive sites do not appear at random but seem to be concentrated in the nucleus, and in the cytoplasm, in areas rich in rough endoplasmic reticulum (RER) elements. Mitochondria were not significantly labelled. Untreated control preparations showed no specific immunogold labelling. After RNase digestion of ultrathin sections obtained from cells exposed to NDMA and subsequent immunogold labelling, most of the immunolabelling in the cytoplasm had disappeared, and that over the nucleus had only been slightly reduced, as compared to undigested specimens from NDMA-treated cultures. After similar digestion with DNase, a strong reduction of the labelling of the nucleus was observed, but labelling of the cytoplasm was practically unaffected by this enzymatic treatment, as compared to what was observed in undigested preparations of NDMA-treated hepatocytes. The results provide evidence of preferential formation of O6-metG at the DNA and RNA levels, in the nucleus and cytoplasm RER, respectively. Furthermore, this study demonstrates the applicability of the high-resolution protein A-gold technique for ultrastructural detection of nucleic acid adducts in NDMA-treated hepatocytes using affinity-purified anti-O6-metG polyclonal antibodies."} {"id": "PMID:1282096", "title": "Hyperphosphorylation of cytokeratins 8 and 18 by microcystin-LR, a new liver tumor promoter, in primary cultured rat hepatocytes.", "content": "Microcystin-LR (MC-LR), an inhibitor of protein phosphatases 1 and 2A, is a potent tumor promoter in rat liver initiated with diethylnitrosamine. To understand its biochemical process in hepatocytes, primary cultured rat hepatocytes were treated with MC-LR. MC-LR (1 microM) induced phosphorylation of various proteins. Two 55 and 49 kDa proteins were phosphorylated at a 3-fold higher rate than other proteins, and these proteins were identified to be cytokeratins 8 and 18 respectively, by immunoprecipitation and Western blot analysis using monoclonal anti-cytokeratin 8 and 18 antibodies. The basic cytokeratins 8 and 18 showed pI 6.4 and 5.4 respectively, in two-dimensional gel electrophoresis. MC-LR dose dependently increased phosphorylation of cytokeratins 8 and 18 in a cell-free system by incubation with a cytosolic fraction of rat liver containing both protein kinases and protein phosphatases 1 and 2A, and with [gamma-32P]ATP. Cytokeratins 8 and 18 were target proteins for phosphorylation induced by inhibition of protein phosphatases 1 and 2A, in vitro and in rat hepatocytes. Thus, the treatment of rat hepatocytes with MC-LR induced hyperphosphorylation of cytokeratins 8 and 18 associated with morphological changes, indicating that intermediate filament networks were rearranged in the cytoplasm. The hyperphosphorylation of cytokeratins is a significant biochemical process associated with liver tumor promotion.", "contents": "Hyperphosphorylation of cytokeratins 8 and 18 by microcystin-LR, a new liver tumor promoter, in primary cultured rat hepatocytes. Microcystin-LR (MC-LR), an inhibitor of protein phosphatases 1 and 2A, is a potent tumor promoter in rat liver initiated with diethylnitrosamine. To understand its biochemical process in hepatocytes, primary cultured rat hepatocytes were treated with MC-LR. MC-LR (1 microM) induced phosphorylation of various proteins. Two 55 and 49 kDa proteins were phosphorylated at a 3-fold higher rate than other proteins, and these proteins were identified to be cytokeratins 8 and 18 respectively, by immunoprecipitation and Western blot analysis using monoclonal anti-cytokeratin 8 and 18 antibodies. The basic cytokeratins 8 and 18 showed pI 6.4 and 5.4 respectively, in two-dimensional gel electrophoresis. MC-LR dose dependently increased phosphorylation of cytokeratins 8 and 18 in a cell-free system by incubation with a cytosolic fraction of rat liver containing both protein kinases and protein phosphatases 1 and 2A, and with [gamma-32P]ATP. Cytokeratins 8 and 18 were target proteins for phosphorylation induced by inhibition of protein phosphatases 1 and 2A, in vitro and in rat hepatocytes. Thus, the treatment of rat hepatocytes with MC-LR induced hyperphosphorylation of cytokeratins 8 and 18 associated with morphological changes, indicating that intermediate filament networks were rearranged in the cytoplasm. The hyperphosphorylation of cytokeratins is a significant biochemical process associated with liver tumor promotion."} {"id": "PMID:1282097", "title": "The usefulness of echocardiography in the surgical management of infants with congenital heart disease.", "content": "Between January 1988 and August 1991, at The Children's Heart Center, Atlanta, 83 infants with congenital heart defects were diagnosed by echocardiography and underwent surgery without cardiac catheterization. The diagnostic categories included 46 infants with left heart obstructive lesions, 19 infants with cyanotic heart lesions, and 18 infants with miscellaneous lesions. Forty-five infants (55%) underwent surgery under cardiopulmonary bypass. There were three errors in diagnosis, yielding a diagnostic accuracy of 95%. Many infants with congenital heart disease can be accurately and completely diagnosed by echocardiography and can safely undergo surgery without cardiac catheterization.", "contents": "The usefulness of echocardiography in the surgical management of infants with congenital heart disease. Between January 1988 and August 1991, at The Children's Heart Center, Atlanta, 83 infants with congenital heart defects were diagnosed by echocardiography and underwent surgery without cardiac catheterization. The diagnostic categories included 46 infants with left heart obstructive lesions, 19 infants with cyanotic heart lesions, and 18 infants with miscellaneous lesions. Forty-five infants (55%) underwent surgery under cardiopulmonary bypass. There were three errors in diagnosis, yielding a diagnostic accuracy of 95%. Many infants with congenital heart disease can be accurately and completely diagnosed by echocardiography and can safely undergo surgery without cardiac catheterization."} {"id": "PMID:1282098", "title": "Insulin administration induces capillary growth in brown adipose tissue of heat-exposed rats.", "content": "1. An apparent effect of insulin administration on enlargement of interscapular brown adipose tissue (BAT) was found in heat-exposed rats, but not in warm-adapted or cold-acclimated rats. 2. BAT extracts from the heat-acclimated/insulin-treated (HI) rats notably increased the capillary growth in an in vitro angiogenesis model in which microvascular fragments and myofibroblastic (Mf) cells isolated from lipid tissues were grown in co-culture, although a direct effect of insulin was not high. 3. BAT extracts from the HI rats stimulated the production of endothelial cell growth factor and collagen by Mf cells. 4. It is probable that an increased angiogenic activity contributes to the capillary growth and tissue growth in BAT of HI rats.", "contents": "Insulin administration induces capillary growth in brown adipose tissue of heat-exposed rats. 1. An apparent effect of insulin administration on enlargement of interscapular brown adipose tissue (BAT) was found in heat-exposed rats, but not in warm-adapted or cold-acclimated rats. 2. BAT extracts from the heat-acclimated/insulin-treated (HI) rats notably increased the capillary growth in an in vitro angiogenesis model in which microvascular fragments and myofibroblastic (Mf) cells isolated from lipid tissues were grown in co-culture, although a direct effect of insulin was not high. 3. BAT extracts from the HI rats stimulated the production of endothelial cell growth factor and collagen by Mf cells. 4. It is probable that an increased angiogenic activity contributes to the capillary growth and tissue growth in BAT of HI rats."} {"id": "PMID:1282099", "title": "Alterations of serum insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBPs) in swine infected with the protozoan parasite Sarcocystis miescheriana.", "content": "The effects of a Sarcocystis miescheriana infection on insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were investigated to determine possible mechanisms of growth retardation in growing pigs. Sixteen pigs averaging 14 kg body weight were divided into 4 groups of 4 pigs each and infected either with 0.5, 1.0, or 3.0 x 10(6) sporocysts of S. miescheriana. Four pigs were retained as non-infected controls; however, they became serologically positive during the course of the infection. Effects also were investigated in 2 groups of 3 pregnant sows. One group was infected with 0.5 x 10(6) sporocysts and the other group was retained as uninfected controls. Body weights of infected growing pigs were depressed as compared to controls following the acute phase 15 d after infection (dai). Serum concentrations of IGF-I dropped significantly (p < 0.05) during the acute phase of infection in all infected groups of growing pigs. Conversely, the amounts of unsaturated serum IGFBPs were elevated significantly (p < 0.05) during the acute phase of infection. Specifically, serum concentrations of IGFBP-1, IGFBP-2, and IGFBP-4 were elevated at this time, as determined by ligand blot analysis. There was no association between growth factor alterations and tissue damage as measured by serum creatinine kinase and aspartate aminotransferase levels. The extent of effects in growing pigs was related to the amount of the original parasite inoculum. During the acute phase of infection 2 of 3 pregnant sows aborted. The third sow went to term, but piglets were stillborn or died within 24 hr. Compared to uninfected controls, serum concentrations of IGF-I in infected pregnant sows were depressed during and after the acute phase of the infection. Levels of unsaturated serum IGFBPs in pregnant sows were not affected. These data suggest that decreased IGF-I levels and/or elevated levels of specific forms of IGFBPs may be a mechanism by which growth is affected in feeder pigs infected with S. miescheriana.", "contents": "Alterations of serum insulin-like growth factor-I (IGF-I) and IGF-binding proteins (IGFBPs) in swine infected with the protozoan parasite Sarcocystis miescheriana. The effects of a Sarcocystis miescheriana infection on insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were investigated to determine possible mechanisms of growth retardation in growing pigs. Sixteen pigs averaging 14 kg body weight were divided into 4 groups of 4 pigs each and infected either with 0.5, 1.0, or 3.0 x 10(6) sporocysts of S. miescheriana. Four pigs were retained as non-infected controls; however, they became serologically positive during the course of the infection. Effects also were investigated in 2 groups of 3 pregnant sows. One group was infected with 0.5 x 10(6) sporocysts and the other group was retained as uninfected controls. Body weights of infected growing pigs were depressed as compared to controls following the acute phase 15 d after infection (dai). Serum concentrations of IGF-I dropped significantly (p < 0.05) during the acute phase of infection in all infected groups of growing pigs. Conversely, the amounts of unsaturated serum IGFBPs were elevated significantly (p < 0.05) during the acute phase of infection. Specifically, serum concentrations of IGFBP-1, IGFBP-2, and IGFBP-4 were elevated at this time, as determined by ligand blot analysis. There was no association between growth factor alterations and tissue damage as measured by serum creatinine kinase and aspartate aminotransferase levels. The extent of effects in growing pigs was related to the amount of the original parasite inoculum. During the acute phase of infection 2 of 3 pregnant sows aborted. The third sow went to term, but piglets were stillborn or died within 24 hr. Compared to uninfected controls, serum concentrations of IGF-I in infected pregnant sows were depressed during and after the acute phase of the infection. Levels of unsaturated serum IGFBPs in pregnant sows were not affected. These data suggest that decreased IGF-I levels and/or elevated levels of specific forms of IGFBPs may be a mechanism by which growth is affected in feeder pigs infected with S. miescheriana."} {"id": "PMID:1282101", "title": "Immunohistochemical expression of subunit beta HCG in breast cancer.", "content": "The ectopic production of HCG by non-trophoblastic tumors is well documented. Adenocarcinomas arising in the mammary gland have been shown to stain positively for the beta subunit of HCG using immunoperoxidase technique. In the present study we used the Monoclonal antibodies (M. abs) H6, H34 and H54 directed against the subunits of this hormone. A total of 31 breast tissue sections from formalin fixed, paraffin embedded unselected material was examined, out of which 22 concerned different types of primary breast cancer (Ca), 5 local recurrences, 3 cystic disease (CD) and one was an axillary lymph node metastasis (LNM). All cases were evaluated for cytoplasmic localization of the beta subunit HCG using the Mab H36 and among the 27 breast Ca 9 were studied with Mab H34 and 6 with Mab H54. Our results with the Mab H6 showed the following: 1) 55.5% of the Ca including the recurrences, were strongly positive (+) and 18.5% weakly positive (+/-); 2) 63.6% of the Grade III tumors were negative (-), whereas 81.2% of the Grade II were +, 18.7% +/- and none was -; 3) It seems that by increasing infiltration of the tumor size positivity is increased; 4) Lymphocytic infiltration of the tumor stroma and LNM did not appear related; 5) From the FU data of 14 cases collected up to now, the 10-year-survival seems to be inconclusive; 6) The 3 cases of CD were negative except for the apocrine cells which were positive; 7) The unique axillary LNM was positive.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Immunohistochemical expression of subunit beta HCG in breast cancer. The ectopic production of HCG by non-trophoblastic tumors is well documented. Adenocarcinomas arising in the mammary gland have been shown to stain positively for the beta subunit of HCG using immunoperoxidase technique. In the present study we used the Monoclonal antibodies (M. abs) H6, H34 and H54 directed against the subunits of this hormone. A total of 31 breast tissue sections from formalin fixed, paraffin embedded unselected material was examined, out of which 22 concerned different types of primary breast cancer (Ca), 5 local recurrences, 3 cystic disease (CD) and one was an axillary lymph node metastasis (LNM). All cases were evaluated for cytoplasmic localization of the beta subunit HCG using the Mab H36 and among the 27 breast Ca 9 were studied with Mab H34 and 6 with Mab H54. Our results with the Mab H6 showed the following: 1) 55.5% of the Ca including the recurrences, were strongly positive (+) and 18.5% weakly positive (+/-); 2) 63.6% of the Grade III tumors were negative (-), whereas 81.2% of the Grade II were +, 18.7% +/- and none was -; 3) It seems that by increasing infiltration of the tumor size positivity is increased; 4) Lymphocytic infiltration of the tumor stroma and LNM did not appear related; 5) From the FU data of 14 cases collected up to now, the 10-year-survival seems to be inconclusive; 6) The 3 cases of CD were negative except for the apocrine cells which were positive; 7) The unique axillary LNM was positive.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282102", "title": "Granulocyte-colony stimulating factor stimulates immunoreactive endothelin-1 release from cultured bovine endothelial cells.", "content": "We examined the effect of human recombinant granulocyte-colony stimulating factor (G-CSF) on the release of immunoreactive endothelin-1 (ET-1) from cultured bovine vascular endothelial cells. G-CSF dose dependently (10(-8)-10(-6) M) increased the release of immunoreactive ET-1 as a function of time under a serum-free condition. Coaddition of G-CSF and thrombin induced an additive effect on immunoreactive ET-1 release. Neither Ca2+ channel antagonist nor cyclooxygenase inhibitor affected immunoreactive ET-1 release stimulated by G-CSF. These results suggest that G-CSF, in addition to its effect on granulocyte progenitors, has a direct effect on vascular endothelium to induce the release of immunoreactive ET-1.", "contents": "Granulocyte-colony stimulating factor stimulates immunoreactive endothelin-1 release from cultured bovine endothelial cells. We examined the effect of human recombinant granulocyte-colony stimulating factor (G-CSF) on the release of immunoreactive endothelin-1 (ET-1) from cultured bovine vascular endothelial cells. G-CSF dose dependently (10(-8)-10(-6) M) increased the release of immunoreactive ET-1 as a function of time under a serum-free condition. Coaddition of G-CSF and thrombin induced an additive effect on immunoreactive ET-1 release. Neither Ca2+ channel antagonist nor cyclooxygenase inhibitor affected immunoreactive ET-1 release stimulated by G-CSF. These results suggest that G-CSF, in addition to its effect on granulocyte progenitors, has a direct effect on vascular endothelium to induce the release of immunoreactive ET-1."} {"id": "PMID:1282103", "title": "Delta-opioid-receptor activation by [D-Pen2,D-Pen5]enkephalin and morphine inhibits substance P release from trigeminal nucleus slices.", "content": "The release of substance P (SP) from spinal dorsal horn slices is partially inhibited by micromolar concentrations of selective delta-opioid receptor agonists. In the present study, we have examined the effect of nanomolar concentrations of [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-opioid receptor agonist) and low micromolar of concentrations morphine on K(+)-evoked SP release from rat trigeminal nucleus caudalis (TNC) slices. DPDPE and morphine inhibited SP release with an apparent maximal effect at 3 nM and at 3 microM, respectively. DPDPE and morphine produced U-shaped concentration-response curves that were completely autoinhibited at 100 nM DPDPE and 1 microM morphine. The inhibition of SP release produced by 3 nM DPDPE and 3 microM morphine was blocked by the opioid receptor antagonists naloxone (30 nM; non-selective) and ICI 174,864 (0.3 microM; delta-selective) but not by nor-binaltorphimine (3 nM n-BNI; kappa-selective), naloxonazine (1 nM; micro 1-selective) or beta-funaltrexamine (20 nM beta-FNA; mu-selective). These findings indicate that delta-opioid receptor-mediated inhibition of SP release from TNC can be achieved by nanomolar concentrations of selective delta-opioid receptor agonists. Activation of delta-opioid receptors by morphine might be involved in the residual analgesia observed after mu 1-opioid receptor blockade and in the analgesia produced by high doses of morphine.", "contents": "Delta-opioid-receptor activation by [D-Pen2,D-Pen5]enkephalin and morphine inhibits substance P release from trigeminal nucleus slices. The release of substance P (SP) from spinal dorsal horn slices is partially inhibited by micromolar concentrations of selective delta-opioid receptor agonists. In the present study, we have examined the effect of nanomolar concentrations of [D-Pen2,D-Pen5]enkephalin (DPDPE, delta-opioid receptor agonist) and low micromolar of concentrations morphine on K(+)-evoked SP release from rat trigeminal nucleus caudalis (TNC) slices. DPDPE and morphine inhibited SP release with an apparent maximal effect at 3 nM and at 3 microM, respectively. DPDPE and morphine produced U-shaped concentration-response curves that were completely autoinhibited at 100 nM DPDPE and 1 microM morphine. The inhibition of SP release produced by 3 nM DPDPE and 3 microM morphine was blocked by the opioid receptor antagonists naloxone (30 nM; non-selective) and ICI 174,864 (0.3 microM; delta-selective) but not by nor-binaltorphimine (3 nM n-BNI; kappa-selective), naloxonazine (1 nM; micro 1-selective) or beta-funaltrexamine (20 nM beta-FNA; mu-selective). These findings indicate that delta-opioid receptor-mediated inhibition of SP release from TNC can be achieved by nanomolar concentrations of selective delta-opioid receptor agonists. Activation of delta-opioid receptors by morphine might be involved in the residual analgesia observed after mu 1-opioid receptor blockade and in the analgesia produced by high doses of morphine."} {"id": "PMID:1282104", "title": "Fluvoxamine preferentially increases extracellular 5-hydroxytryptamine in the raphe nuclei: an in vivo microdialysis study.", "content": "The effects of systemic administration of fluvoxamine on extracellular serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the frontal cortex and raphe nuclei of freely moving rats were examined. Fluvoxamine significantly increased extracellular 5-HT concentrations in both regions at the two doses used (1 and 10 mg/kg i.p.). However, the increase in the raphe nuclei was several-fold that in the frontal cortex. Dialysate 5-HIAA concentrations decreased after treatment with fluvoxamine. These results confirm that 5-HT uptake inhibitors preferentially increase extracellular concentrations of 5-HT in the vicinity of cell bodies and dendrites of serotonergic neurones.", "contents": "Fluvoxamine preferentially increases extracellular 5-hydroxytryptamine in the raphe nuclei: an in vivo microdialysis study. The effects of systemic administration of fluvoxamine on extracellular serotonin (5-hydroxytryptamine, 5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the frontal cortex and raphe nuclei of freely moving rats were examined. Fluvoxamine significantly increased extracellular 5-HT concentrations in both regions at the two doses used (1 and 10 mg/kg i.p.). However, the increase in the raphe nuclei was several-fold that in the frontal cortex. Dialysate 5-HIAA concentrations decreased after treatment with fluvoxamine. These results confirm that 5-HT uptake inhibitors preferentially increase extracellular concentrations of 5-HT in the vicinity of cell bodies and dendrites of serotonergic neurones."} {"id": "PMID:1282105", "title": "CR 2039, a new bis-(1H-tetrazol-5-yl)phenylbenzamide derivative with potential for the topical treatment of asthma.", "content": "The pharmacological activity of CR 2039 (4-(1H-tetrazol-5-yl)-N-(4-[1H-tetrazol-5-yl]phenylbenzam ide)) a newly discovered antiallergic compound is described. CR 2039 administered i.m. or i.v. inhibited rat passive cutaneous anaphylaxis (PCA) with an ED50 of 0.1 mg/kg and a potency about 15 times higher than that of disodium cromoglycate (DSCG). CR 2039 i.m., by aerosol or as dry powder insufflation, gave dose-related significant protection against IgE-dependent bronchial anaphylaxis induced by aerosolized antigen in anesthetized guinea-pigs. In conscious guinea-pigs CR 2039 given i.m. delayed dose dependently (ED50, 17 mg/kg) the onset of bronchoconstriction induced by aerosolized antigen, while DSCG was ineffective up to 100 mg/kg. The protection was accompanied by significant inhibition of the vascular permeability provoked by antigen challenge in all airway segments except trachea. CR 2039 (10-100 mg/kg i.v.) inhibited the microvascular permeability changes in a model of allergic conjunctivitis in sensitized guinea-pigs. CR 2039 inhibited dose dependently guinea-pig lung cAMP-phosphodiesterase with an IC50 of 50 microM.", "contents": "CR 2039, a new bis-(1H-tetrazol-5-yl)phenylbenzamide derivative with potential for the topical treatment of asthma. The pharmacological activity of CR 2039 (4-(1H-tetrazol-5-yl)-N-(4-[1H-tetrazol-5-yl]phenylbenzam ide)) a newly discovered antiallergic compound is described. CR 2039 administered i.m. or i.v. inhibited rat passive cutaneous anaphylaxis (PCA) with an ED50 of 0.1 mg/kg and a potency about 15 times higher than that of disodium cromoglycate (DSCG). CR 2039 i.m., by aerosol or as dry powder insufflation, gave dose-related significant protection against IgE-dependent bronchial anaphylaxis induced by aerosolized antigen in anesthetized guinea-pigs. In conscious guinea-pigs CR 2039 given i.m. delayed dose dependently (ED50, 17 mg/kg) the onset of bronchoconstriction induced by aerosolized antigen, while DSCG was ineffective up to 100 mg/kg. The protection was accompanied by significant inhibition of the vascular permeability provoked by antigen challenge in all airway segments except trachea. CR 2039 (10-100 mg/kg i.v.) inhibited the microvascular permeability changes in a model of allergic conjunctivitis in sensitized guinea-pigs. CR 2039 inhibited dose dependently guinea-pig lung cAMP-phosphodiesterase with an IC50 of 50 microM."} {"id": "PMID:1282106", "title": "Enzymatic kinetic studies with the non-nucleoside HIV reverse transcriptase inhibitor U-9843.", "content": "The polymer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT (reverse transcriptase) and the drug possesses excellent antiviral activity at nontoxic doses in HIV-infected lymphocytes grown in tissue culture. The drug also inhibits RTs isolated from other species such as AMV and MLV retroviruses. Enzymatic kinetic studies of the HIV-1 RT catalyzed RNA-directed DNA polymerase function, using synthetic template:primers, indicate that the drug acts generally noncompetitively with respect to the template:primer binding site but the specific inhibition patterns change somewhat depending on the drug concentration. The inhibitor acts noncompetitively with respect to the dNTP binding sites. Hence, the drug inhibits this RT polymerase function by interacting with a site distinct from the template:primer and dNTP binding sites. In addition, the inhibitor also impairs the DNA-dependent DNA polymerase activity of HIV-1 RT and the RNase H function. This indicates that the drug interacts with a target site essential for all three HIV RT functions addressed (RNA- and DNA-directed DNA polymerases, RNase H).", "contents": "Enzymatic kinetic studies with the non-nucleoside HIV reverse transcriptase inhibitor U-9843. The polymer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT (reverse transcriptase) and the drug possesses excellent antiviral activity at nontoxic doses in HIV-infected lymphocytes grown in tissue culture. The drug also inhibits RTs isolated from other species such as AMV and MLV retroviruses. Enzymatic kinetic studies of the HIV-1 RT catalyzed RNA-directed DNA polymerase function, using synthetic template:primers, indicate that the drug acts generally noncompetitively with respect to the template:primer binding site but the specific inhibition patterns change somewhat depending on the drug concentration. The inhibitor acts noncompetitively with respect to the dNTP binding sites. Hence, the drug inhibits this RT polymerase function by interacting with a site distinct from the template:primer and dNTP binding sites. In addition, the inhibitor also impairs the DNA-dependent DNA polymerase activity of HIV-1 RT and the RNase H function. This indicates that the drug interacts with a target site essential for all three HIV RT functions addressed (RNA- and DNA-directed DNA polymerases, RNase H)."} {"id": "PMID:1282107", "title": "Cyclosporine is angiostatic.", "content": "The systemic effect of the immunosuppressive drug cyclosporine (CS) on formation of new blood vessels was studied quantitatively in rats using the mesenteric-window assay. Angiogenesis was induced by i.p. injection of saline. CS at a s.c. dose of 4 mg/kg/day, which is in the range used clinically, suppressed angiogenesis (inhibiting branching or tortuosity more than spatial expansion), and appeared to be non-toxic. This is the first report on an apparently selective angiostatic effect of CS. The finding is likely to have implications for the clinical use of CS, not only in certain types of organ transplantation but possibly also in psoriasis and other angiogenesis-dependent diseases.", "contents": "Cyclosporine is angiostatic. The systemic effect of the immunosuppressive drug cyclosporine (CS) on formation of new blood vessels was studied quantitatively in rats using the mesenteric-window assay. Angiogenesis was induced by i.p. injection of saline. CS at a s.c. dose of 4 mg/kg/day, which is in the range used clinically, suppressed angiogenesis (inhibiting branching or tortuosity more than spatial expansion), and appeared to be non-toxic. This is the first report on an apparently selective angiostatic effect of CS. The finding is likely to have implications for the clinical use of CS, not only in certain types of organ transplantation but possibly also in psoriasis and other angiogenesis-dependent diseases."} {"id": "PMID:1282108", "title": "Differential effects of granulocyte- and granulocyte-macrophage colony-stimulating factors (G- and GM-CSF) on neutrophil adhesion in vitro and in vivo.", "content": "A direct comparison of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) effects on neutrophil adhesiveness has been carried out. In vitro, GM-CSF and G-CSF upregulate neutrophil CD11b to a similar degree (to 227 +/- 69%, and 232 +/- 70% of control cells, respectively, p < 0.0005), but GM-CSF is more effective in downregulating neutrophil leucocyte adhesion molecule-1 (LAM-1), reducing levels to 33 +/- 4% (p < 0.0005), while G-CSF causes a fall to only 65 +/- 17% (p < 0.005) of control. The concentration of GM-CSF needed to achieve maximal activity is at least one log less than that of G-CSF. In vivo, both GM-CSF and G-CSF upregulate neutrophil CD11b (to 296 +/- 45% and 370 +/- 150%, respectively of baseline), but surface levels of LAM-1 on circulating cells are unchanged. GM-CSF increased neutrophil adhesion to cultured human endothelium in vitro (from 9.3 +/- 0.7% to 15.4 +/- 1.3%, p < 0.0005, n = 10), while G-CSF was without effect. In vivo, both GM-CSF and G-CSF produce a transient leucopenia, but recovery of peripheral counts occurs much earlier (by 60 minutes) with G-CSF, than with GM-CSF (only 50% of cells have demarginated at 120 min). GM-CSF appears to be greater proadhesive agonist for neutrophils than G-CSF.", "contents": "Differential effects of granulocyte- and granulocyte-macrophage colony-stimulating factors (G- and GM-CSF) on neutrophil adhesion in vitro and in vivo. A direct comparison of granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) effects on neutrophil adhesiveness has been carried out. In vitro, GM-CSF and G-CSF upregulate neutrophil CD11b to a similar degree (to 227 +/- 69%, and 232 +/- 70% of control cells, respectively, p < 0.0005), but GM-CSF is more effective in downregulating neutrophil leucocyte adhesion molecule-1 (LAM-1), reducing levels to 33 +/- 4% (p < 0.0005), while G-CSF causes a fall to only 65 +/- 17% (p < 0.005) of control. The concentration of GM-CSF needed to achieve maximal activity is at least one log less than that of G-CSF. In vivo, both GM-CSF and G-CSF upregulate neutrophil CD11b (to 296 +/- 45% and 370 +/- 150%, respectively of baseline), but surface levels of LAM-1 on circulating cells are unchanged. GM-CSF increased neutrophil adhesion to cultured human endothelium in vitro (from 9.3 +/- 0.7% to 15.4 +/- 1.3%, p < 0.0005, n = 10), while G-CSF was without effect. In vivo, both GM-CSF and G-CSF produce a transient leucopenia, but recovery of peripheral counts occurs much earlier (by 60 minutes) with G-CSF, than with GM-CSF (only 50% of cells have demarginated at 120 min). GM-CSF appears to be greater proadhesive agonist for neutrophils than G-CSF."} {"id": "PMID:1282109", "title": "Interaction of trans-acting factors with the proximal promoter of the mouse alpha-fetoprotein gene.", "content": "1. The alpha-Fetoprotein (AFP) gene is expressed during fetal life, but not in adult cells. Also, the AFP gene is expressed in most hepatomas. 2. Using gel retardation (band-shift) assays under very stringent conditions we have compared the binding of trans-acting factors to the proximal enhancer (-202, +34) region of the AFP gene. 3. We have detected the presence of two retarded bands in experiments performed with adult rat hepatocytes and the Fa32 cell line (which does not produce AFP) but only one band is observed with the HepG2 cell line (which produces AFP) and fetal liver. 4. We relate the two retarded bands to a glucocorticoid response element and, tentatively, to the C/EBP trans-acting fractor.", "contents": "Interaction of trans-acting factors with the proximal promoter of the mouse alpha-fetoprotein gene. 1. The alpha-Fetoprotein (AFP) gene is expressed during fetal life, but not in adult cells. Also, the AFP gene is expressed in most hepatomas. 2. Using gel retardation (band-shift) assays under very stringent conditions we have compared the binding of trans-acting factors to the proximal enhancer (-202, +34) region of the AFP gene. 3. We have detected the presence of two retarded bands in experiments performed with adult rat hepatocytes and the Fa32 cell line (which does not produce AFP) but only one band is observed with the HepG2 cell line (which produces AFP) and fetal liver. 4. We relate the two retarded bands to a glucocorticoid response element and, tentatively, to the C/EBP trans-acting fractor."} {"id": "PMID:1282110", "title": "Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans.", "content": "The involvement of nitric oxide as an intracellular messenger in the control of insulin secretion from pancreatic Beta cells was studied in rat islets of Langerhans by measuring: (i) nitric oxide generation in response to physiological insulin secretagogues; (ii) the effects of inhibitors of nitric oxide synthesis on insulin secretory responses to physiological secretagogues, and on insulin synthesis; (iii) changes in islet cyclic guanosine monophosphate in response to secretagogues; (iv) the effects of exogenous cyclic guanosine monophosphate and dibutyryl cyclic guanosine monophosphate on insulin secretion from electrically permeabilised islets and from intact, respectively. These studies produced no evidence that nitric oxide generation is required for the initiation of insulin secretion by common secretagogues. However, the results of our experiments suggest that the generation of nitric oxide may be involved in long-term, glucose-dependent increases in cyclic guanosine monophosphate content of islet cells, although the physiological relevance of these changes requires further investigation.", "contents": "Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans. The involvement of nitric oxide as an intracellular messenger in the control of insulin secretion from pancreatic Beta cells was studied in rat islets of Langerhans by measuring: (i) nitric oxide generation in response to physiological insulin secretagogues; (ii) the effects of inhibitors of nitric oxide synthesis on insulin secretory responses to physiological secretagogues, and on insulin synthesis; (iii) changes in islet cyclic guanosine monophosphate in response to secretagogues; (iv) the effects of exogenous cyclic guanosine monophosphate and dibutyryl cyclic guanosine monophosphate on insulin secretion from electrically permeabilised islets and from intact, respectively. These studies produced no evidence that nitric oxide generation is required for the initiation of insulin secretion by common secretagogues. However, the results of our experiments suggest that the generation of nitric oxide may be involved in long-term, glucose-dependent increases in cyclic guanosine monophosphate content of islet cells, although the physiological relevance of these changes requires further investigation."} {"id": "PMID:1282111", "title": "Expression of c-kit, a proto-oncogene of the murine W locus, in cerebella of normal and neurological mutant mice: immunohistochemical and in situ hybridization analysis.", "content": "The c-kit proto-oncogene encodes a receptor tyrosine kinase and is allelic with the murine white-spoting (W) locus. Although no apparent defects in the brain have been reported in W mutant mice, brain tissue, especially cerebellum, shows a high level of c-kit transcription. In the present study, sites of c-kit expression in the cerebellum were exained by immunohistochemical and in situ hybridization techniques. Immunohistochemistry with a monoclonal antibody against c-Kit protein revealed that the c-Kit protein was localized close to the Purkinje cell soma in the region facing the granular cell layer. Similar distribution of the c-Kit protein was observed in cerebella of mutant mice in which the Purkinje cell (pcd) or the granular cell layer (weaver) is missing. These data suggest that the c-Kit protein is produced not by the Purkinje cell nor by the granular cell but by the cells present in the molecular layer and that the protein is then transported to the region around the Purkinje cell soma. This interpretation was supported by in situ hybridization analysis: cells containing the c-kit transcripts were found only in the molecular layer, while the granular and Purkinje cells were negative.", "contents": "Expression of c-kit, a proto-oncogene of the murine W locus, in cerebella of normal and neurological mutant mice: immunohistochemical and in situ hybridization analysis. The c-kit proto-oncogene encodes a receptor tyrosine kinase and is allelic with the murine white-spoting (W) locus. Although no apparent defects in the brain have been reported in W mutant mice, brain tissue, especially cerebellum, shows a high level of c-kit transcription. In the present study, sites of c-kit expression in the cerebellum were exained by immunohistochemical and in situ hybridization techniques. Immunohistochemistry with a monoclonal antibody against c-Kit protein revealed that the c-Kit protein was localized close to the Purkinje cell soma in the region facing the granular cell layer. Similar distribution of the c-Kit protein was observed in cerebella of mutant mice in which the Purkinje cell (pcd) or the granular cell layer (weaver) is missing. These data suggest that the c-Kit protein is produced not by the Purkinje cell nor by the granular cell but by the cells present in the molecular layer and that the protein is then transported to the region around the Purkinje cell soma. This interpretation was supported by in situ hybridization analysis: cells containing the c-kit transcripts were found only in the molecular layer, while the granular and Purkinje cells were negative."} {"id": "PMID:1282112", "title": "Suprabasal marker proteins distinguishing keratinizing squamous epithelia: cytokeratin 2 polypeptides of oral masticatory epithelium and epidermis are different.", "content": "Terminal differentiation of squamous epithelia is usually characterized by the synthesis of a subset of cytokeratins (CKs) in suprabasal cell layers which become major components of the intermediate filament (IF) bundle cytoskeleton of the maturing cells. We have examined the significance, molecular nature and pattern of synthesis of the elusive human CK 2 by analyzing mRNAs from certain stratified epithelia, using in vitro translation, cDNA cloning. Northern blotting and in situ hybridization. We show that genuine polypeptides with the typical gel electrophoretic mobility of CK 2 exist but that the CK 2 present in the masticatory epithelia of hard palate and gingiva (CK 2p) differs from that found in epidermis (CK 2e) by its amino acid sequence and is encoded by a different gene. The two CKs 2 show only limited sequence homology (71% identical amino acid positions in the rod domain), and the oral CK 2p is more closely related to the corneal CK 3 (86%), as is also indicated by the cross-reaction of monoclonal antibody AE5. By in situ hybridization and immunocytochemistry, we further show that both CK 2e and CK 2p are expressed only in suprabasal cell layers of the specific epithelia where they can accumulate to represent major cytoskeletal proteins. We discuss this tissue-type specificity of CK 2 synthesis in otherwise morphologically and biochemically similar epithelia in relation to differences of IF appearance and packing in upper strata between epidermal and masticatory epithelia as well as to tissue formation and differentiation during development.", "contents": "Suprabasal marker proteins distinguishing keratinizing squamous epithelia: cytokeratin 2 polypeptides of oral masticatory epithelium and epidermis are different. Terminal differentiation of squamous epithelia is usually characterized by the synthesis of a subset of cytokeratins (CKs) in suprabasal cell layers which become major components of the intermediate filament (IF) bundle cytoskeleton of the maturing cells. We have examined the significance, molecular nature and pattern of synthesis of the elusive human CK 2 by analyzing mRNAs from certain stratified epithelia, using in vitro translation, cDNA cloning. Northern blotting and in situ hybridization. We show that genuine polypeptides with the typical gel electrophoretic mobility of CK 2 exist but that the CK 2 present in the masticatory epithelia of hard palate and gingiva (CK 2p) differs from that found in epidermis (CK 2e) by its amino acid sequence and is encoded by a different gene. The two CKs 2 show only limited sequence homology (71% identical amino acid positions in the rod domain), and the oral CK 2p is more closely related to the corneal CK 3 (86%), as is also indicated by the cross-reaction of monoclonal antibody AE5. By in situ hybridization and immunocytochemistry, we further show that both CK 2e and CK 2p are expressed only in suprabasal cell layers of the specific epithelia where they can accumulate to represent major cytoskeletal proteins. We discuss this tissue-type specificity of CK 2 synthesis in otherwise morphologically and biochemically similar epithelia in relation to differences of IF appearance and packing in upper strata between epidermal and masticatory epithelia as well as to tissue formation and differentiation during development."} {"id": "PMID:1282113", "title": "Endoscopic diagnosis of early carcinoma of the esophagus using Lugol's solution.", "content": "Small esophageal lesions, particularly intraepithelial cancers, are extremely difficult to detect. We used Lugol's iodine solution with panendoscopic examination to detect the presence and spread of small squamous cell carcinomas of the esophagus. Serial histologic specimens of the surgically removed esophagus from 32 patients with Lugol's combined endoscopic diagnosis of early esophageal carcinoma were examined to determine the correlation between endoscopic and histologic findings. All of the early staged carcinomas clearly remained unstained by Lugol's solution. We believe that the application of Lugol's solution will greatly aid in instances when a suspicious mucosal lesion is noted, when the margin of the lesion is unclear, or when there is suspicion that a mucosal lesion may have been overlooked.", "contents": "Endoscopic diagnosis of early carcinoma of the esophagus using Lugol's solution. Small esophageal lesions, particularly intraepithelial cancers, are extremely difficult to detect. We used Lugol's iodine solution with panendoscopic examination to detect the presence and spread of small squamous cell carcinomas of the esophagus. Serial histologic specimens of the surgically removed esophagus from 32 patients with Lugol's combined endoscopic diagnosis of early esophageal carcinoma were examined to determine the correlation between endoscopic and histologic findings. All of the early staged carcinomas clearly remained unstained by Lugol's solution. We believe that the application of Lugol's solution will greatly aid in instances when a suspicious mucosal lesion is noted, when the margin of the lesion is unclear, or when there is suspicion that a mucosal lesion may have been overlooked."} {"id": "PMID:1282114", "title": "Cuffed esophageal prosthesis: a useful device in desperate situations in esophageal malignancy.", "content": "Sixteen patients (three groups) underwent endoscopic intubation with cuffed Wilson-Cook esophageal endoprostheses. Group 1 comprised 10 patients with spontaneous esophago-respiratory fistulas due to malignancy. Six primaries were esophageal, three bronchial and one ovarian. One patient could not tolerate a cuffed tube. All other fistulas closed with intubation but two tubes displaced later. Seven patients managed a soft diet after intubation, but two liquids only. Median survival was 4 weeks (range, 0 to 9 weeks). Group 2 comprised three patients with large endoscopic instrumental tears. Two had definite perforations with extensive surgical emphysema. All had satisfactory contrast swallows the day after intubation and were started on semi-solid diets; median survival was 10 weeks (one still alive). Group 3 included three patients with life-threatening arterial bleeding from cancers of the gastric cardia. No further bleeding occurred in any of the three after intubation and two survived for extended periods (15 and 26 weeks). Cuffed tubes are invaluable in these desperate situations and are worth considering for symptomatic relief even when prognosis is short.", "contents": "Cuffed esophageal prosthesis: a useful device in desperate situations in esophageal malignancy. Sixteen patients (three groups) underwent endoscopic intubation with cuffed Wilson-Cook esophageal endoprostheses. Group 1 comprised 10 patients with spontaneous esophago-respiratory fistulas due to malignancy. Six primaries were esophageal, three bronchial and one ovarian. One patient could not tolerate a cuffed tube. All other fistulas closed with intubation but two tubes displaced later. Seven patients managed a soft diet after intubation, but two liquids only. Median survival was 4 weeks (range, 0 to 9 weeks). Group 2 comprised three patients with large endoscopic instrumental tears. Two had definite perforations with extensive surgical emphysema. All had satisfactory contrast swallows the day after intubation and were started on semi-solid diets; median survival was 10 weeks (one still alive). Group 3 included three patients with life-threatening arterial bleeding from cancers of the gastric cardia. No further bleeding occurred in any of the three after intubation and two survived for extended periods (15 and 26 weeks). Cuffed tubes are invaluable in these desperate situations and are worth considering for symptomatic relief even when prognosis is short."} {"id": "PMID:1282117", "title": "[Significance of the maternal levels of serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol in various congenital developmental defects in pregnancy trimester II].", "content": "Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG) and unconjugated oestriol (uE3) concentrations were measured in maternal serum samples from 21 pregnancies with neural-tube defects, 4 pregnancies with ventral wall defects (VWD) and 1662 unaffected pregnancies in women. These congenital malformations were confirmed by ultrasound scanning. The mean multiplate of the median (MoM) for AFP and uE3 was significantly different from the control values in cases of open NTD (AFP median MoM = 5.95, p < 0.001, uE3 median MoM = 0.2, p < 0.001), while hCG values did not differ from those of matched controls (hCG median MoM = 0.9). The biological basis of altered levels of uE3 in pregnancies with fetal NTDs is unclear.", "contents": "[Significance of the maternal levels of serum alpha-fetoprotein, human chorionic gonadotropin and unconjugated estriol in various congenital developmental defects in pregnancy trimester II]. Maternal serum alpha-fetoprotein (MSAFP), human chorionic gonadotropin (hCG) and unconjugated oestriol (uE3) concentrations were measured in maternal serum samples from 21 pregnancies with neural-tube defects, 4 pregnancies with ventral wall defects (VWD) and 1662 unaffected pregnancies in women. These congenital malformations were confirmed by ultrasound scanning. The mean multiplate of the median (MoM) for AFP and uE3 was significantly different from the control values in cases of open NTD (AFP median MoM = 5.95, p < 0.001, uE3 median MoM = 0.2, p < 0.001), while hCG values did not differ from those of matched controls (hCG median MoM = 0.9). The biological basis of altered levels of uE3 in pregnancies with fetal NTDs is unclear."} {"id": "PMID:1282118", "title": "Glial cell localization of acidic fibroblast growth factor-like immunoreactivity in the optic nerve of young adult and aged mammals.", "content": "The number of axons in the optic nerve decreases with age and this degeneration is greater in patients suffering from Alzheimer's disease. Alterations in the role of neurotrophic factors could lead to this degeneration. Acidic fibroblast growth factor (aFGF)-like immunoreactivity was examined by indirect immunofluorescence on cryostat sections incubated with a rabbit polyclonal antiserum specific for aFGF. Staining was observed by photonic microscopy on optic nerves of Wistar rats (1- to 25-month-old), bovine animals (0.5- to 7-year-old) and normal human adults (24-, 34-, 54- and 84-year-old). In the three species studied, the results show that (1) glial cells were stained in the nuclear region and (2) aFGF-like immuno-reactivity was present over a large age span in adult subjects. Endogenous aFGF may have trophic effects on retinal ganglion cells and their axons throughout the adult life span.", "contents": "Glial cell localization of acidic fibroblast growth factor-like immunoreactivity in the optic nerve of young adult and aged mammals. The number of axons in the optic nerve decreases with age and this degeneration is greater in patients suffering from Alzheimer's disease. Alterations in the role of neurotrophic factors could lead to this degeneration. Acidic fibroblast growth factor (aFGF)-like immunoreactivity was examined by indirect immunofluorescence on cryostat sections incubated with a rabbit polyclonal antiserum specific for aFGF. Staining was observed by photonic microscopy on optic nerves of Wistar rats (1- to 25-month-old), bovine animals (0.5- to 7-year-old) and normal human adults (24-, 34-, 54- and 84-year-old). In the three species studied, the results show that (1) glial cells were stained in the nuclear region and (2) aFGF-like immuno-reactivity was present over a large age span in adult subjects. Endogenous aFGF may have trophic effects on retinal ganglion cells and their axons throughout the adult life span."} {"id": "PMID:1282119", "title": "21-day intravenous toxicity study with feline interferon in rats.", "content": "The toxicity of recombinant feline interferon, a prospective antiviral drug for cats, was examined in a subacute study. Groups of five male and five female Wistar rats were given iv feline interferon in 20 mM-NaCl at doses of 0, 5, 15 and 50 MU/kg body weight/day for 21 consecutive days. Criteria to assess toxicity included clinical observations, ophthalmoscopy, growth, food and water intake, haematology, clinical chemistry, urinalysis, organ weights, gross examination at autopsy and microscopic examination of the liver, kidneys, spleen, adrenals, heart, mesenteric lymph nodes and thymus. No treatment-related were observed even at the highest dose level. The no-observed-adverse-effect level for feline interferon in this study was therefore 50 MU/kg body weight/day.", "contents": "21-day intravenous toxicity study with feline interferon in rats. The toxicity of recombinant feline interferon, a prospective antiviral drug for cats, was examined in a subacute study. Groups of five male and five female Wistar rats were given iv feline interferon in 20 mM-NaCl at doses of 0, 5, 15 and 50 MU/kg body weight/day for 21 consecutive days. Criteria to assess toxicity included clinical observations, ophthalmoscopy, growth, food and water intake, haematology, clinical chemistry, urinalysis, organ weights, gross examination at autopsy and microscopic examination of the liver, kidneys, spleen, adrenals, heart, mesenteric lymph nodes and thymus. No treatment-related were observed even at the highest dose level. The no-observed-adverse-effect level for feline interferon in this study was therefore 50 MU/kg body weight/day."} {"id": "PMID:1282120", "title": "In vivo measurement of endothelium-dependent vasodilation with substance P in man.", "content": "Endothelial cells synthesize and metabolize vasoactive substances which are involved in the regulation of vascular tone. Among these factors, the endothelium-derived nitric oxide (NO) appears to be of major importance. Many studies observed an impairment of the generation, release, or the diffusion of endothelial NO across the vascular intima in laboratory animals with various experimental diseases such as hypercholesterolemia, atherosclerosis and hypertension. In human coronary arteries obtained from explanted hearts impaired endothelium-dependent relaxations were measured in atherosclerotic segments. The hypothesis of a decreased NO mediated vasodilation in patients with coronary artery disease was further underscored by in vivo studies in man using intracoronary infusions of the endothelium-dependent vasodilator acetylcholine and quantitative coronary angiographic measurements of the diameter changes. From these observations it was assumed that endothelial dysfunction, in particular a profound inability of the coronary endothelium to relax via NO dependent mechanisms may play an important role in the pathogenesis of abnormal coronary vasomotion. However, further investigations in man reveal that the ability of the coronary endothelium of patients with coronary artery disease or vasospastic angina to produce endothelial NO is less affected as judged from the effects of acetylcholine. In recent investigations a largely preserved endothelial function could be measured in these patients when the endothelium-dependent vasodilator substance P was used as a tool for the measurement of NO dependent relaxation. Thus, endothelial dysfunction does not appear to serve as a major cause of abnormal vasoconstriction in coronary artery disease or vasospastic angina in man.", "contents": "In vivo measurement of endothelium-dependent vasodilation with substance P in man. Endothelial cells synthesize and metabolize vasoactive substances which are involved in the regulation of vascular tone. Among these factors, the endothelium-derived nitric oxide (NO) appears to be of major importance. Many studies observed an impairment of the generation, release, or the diffusion of endothelial NO across the vascular intima in laboratory animals with various experimental diseases such as hypercholesterolemia, atherosclerosis and hypertension. In human coronary arteries obtained from explanted hearts impaired endothelium-dependent relaxations were measured in atherosclerotic segments. The hypothesis of a decreased NO mediated vasodilation in patients with coronary artery disease was further underscored by in vivo studies in man using intracoronary infusions of the endothelium-dependent vasodilator acetylcholine and quantitative coronary angiographic measurements of the diameter changes. From these observations it was assumed that endothelial dysfunction, in particular a profound inability of the coronary endothelium to relax via NO dependent mechanisms may play an important role in the pathogenesis of abnormal coronary vasomotion. However, further investigations in man reveal that the ability of the coronary endothelium of patients with coronary artery disease or vasospastic angina to produce endothelial NO is less affected as judged from the effects of acetylcholine. In recent investigations a largely preserved endothelial function could be measured in these patients when the endothelium-dependent vasodilator substance P was used as a tool for the measurement of NO dependent relaxation. Thus, endothelial dysfunction does not appear to serve as a major cause of abnormal vasoconstriction in coronary artery disease or vasospastic angina in man."} {"id": "PMID:1282121", "title": "Circumdural decompression by posterior vertebrectomy for relief of cord compression due to metastatic disease of thoracic and lumbar spine.", "content": "Circumdural cord decompression with total or almost total vertebrectomy in the thoracic or lumbar spine through a posterior approach can provide optimal decompression of neural tissue. This procedure combined with posterior instrumentation and immediate reconstruction of the anterior defect with polymethylmethacrylate can provide adequate stabilization. Immediate ambulation with minimal external support is possible. This single operative approach is preferred to anterior (transthoracic or retroperitoneal) decompression due to high morbidity associated with the latter. The authors' experience with this procedure in four cases is presented.", "contents": "Circumdural decompression by posterior vertebrectomy for relief of cord compression due to metastatic disease of thoracic and lumbar spine. Circumdural cord decompression with total or almost total vertebrectomy in the thoracic or lumbar spine through a posterior approach can provide optimal decompression of neural tissue. This procedure combined with posterior instrumentation and immediate reconstruction of the anterior defect with polymethylmethacrylate can provide adequate stabilization. Immediate ambulation with minimal external support is possible. This single operative approach is preferred to anterior (transthoracic or retroperitoneal) decompression due to high morbidity associated with the latter. The authors' experience with this procedure in four cases is presented."} {"id": "PMID:1282122", "title": "Intellectual and developmental assessment of cerebral palsy cases in Libyan city.", "content": "This study was undertaken to evaluate the pattern of cerebral palsy (CP) cases seen at Children's Hospital, benghazi, Libya, in respect of age and sex distribution and developmental outcome according to the type of CP and in various diseases. 60 children both male and female with CP were examined for developmental and intellectual impairment responsible for severe learning and psychomotor disabilities and to their linguistic disorder. Diagnosis of CP was made by a detailed history, physical examination and relevant laboratory investigations. Intellectual and developmental assessment of all CP cases were done by psychometry. CPs are motor syndromes, and not diseases. They are commonly associated with sensory or cognitive defects and epilepsies. The CP children when compared with normal are significant at 0.01 level of significance IQ's and DQ's. Only 8% children with mild to borderline intellectual impairment had mild speech delay an darticulation defects, and showed learning disability. 40% children with sensory disorder had variations from moderate to borderline intellectual subnormality and 36% children with birth asphyxia had delayed milestones thought were felt to have motor problems initially.", "contents": "Intellectual and developmental assessment of cerebral palsy cases in Libyan city. This study was undertaken to evaluate the pattern of cerebral palsy (CP) cases seen at Children's Hospital, benghazi, Libya, in respect of age and sex distribution and developmental outcome according to the type of CP and in various diseases. 60 children both male and female with CP were examined for developmental and intellectual impairment responsible for severe learning and psychomotor disabilities and to their linguistic disorder. Diagnosis of CP was made by a detailed history, physical examination and relevant laboratory investigations. Intellectual and developmental assessment of all CP cases were done by psychometry. CPs are motor syndromes, and not diseases. They are commonly associated with sensory or cognitive defects and epilepsies. The CP children when compared with normal are significant at 0.01 level of significance IQ's and DQ's. Only 8% children with mild to borderline intellectual impairment had mild speech delay an darticulation defects, and showed learning disability. 40% children with sensory disorder had variations from moderate to borderline intellectual subnormality and 36% children with birth asphyxia had delayed milestones thought were felt to have motor problems initially."} {"id": "PMID:1282124", "title": "Effect of the NEP inhibitor SCH32615 on airway responses to intravenous substance P in guinea pigs.", "content": "We examined the effects of the selective neutral endopeptidase (NEP) inhibitor SCH32615 on airway responses to rapid intravenous infusions of substance P (SP) and neurokinin A (NKA) and on recovery of administered tachykinins from arterial blood in anesthetized mechanically ventilated guinea pigs. SCH32615, in doses that cause a marked increase in the magnitude of bronchoconstriction induced by infused NKA, had little effect on the changes in pulmonary conductance (GL) or dynamic compliance induced by SP. In animals in which SCH32615 (1 mg/kg) was administered in combination with the angiotensin-converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), the dose of SP required to decrease GL by 50% was fourfold less than in animals that received captopril alone (P < 0.005). SP measured in arterial blood withdrawn within 45 s of intravenous administration of this tachykinin was not different in control and SCH32615-treated animals, whereas captopril caused an approximately threefold increase in SP concentrations (P < 0.005). When SCH32615 and captopril were administered together, significantly more SP was recovered than when captopril or SCH32615 was administered alone (P < 0.0005). Our results are consistent with the hypothesis that both NEP and ACE contribute to the degradation of intravenously infused SP. ACE degradation of SP is sufficient to limit SP-induced bronchoconstriction even in the presence of specific NEP inhibition.", "contents": "Effect of the NEP inhibitor SCH32615 on airway responses to intravenous substance P in guinea pigs. We examined the effects of the selective neutral endopeptidase (NEP) inhibitor SCH32615 on airway responses to rapid intravenous infusions of substance P (SP) and neurokinin A (NKA) and on recovery of administered tachykinins from arterial blood in anesthetized mechanically ventilated guinea pigs. SCH32615, in doses that cause a marked increase in the magnitude of bronchoconstriction induced by infused NKA, had little effect on the changes in pulmonary conductance (GL) or dynamic compliance induced by SP. In animals in which SCH32615 (1 mg/kg) was administered in combination with the angiotensin-converting enzyme (ACE) inhibitor captopril (5.7 mg/kg), the dose of SP required to decrease GL by 50% was fourfold less than in animals that received captopril alone (P < 0.005). SP measured in arterial blood withdrawn within 45 s of intravenous administration of this tachykinin was not different in control and SCH32615-treated animals, whereas captopril caused an approximately threefold increase in SP concentrations (P < 0.005). When SCH32615 and captopril were administered together, significantly more SP was recovered than when captopril or SCH32615 was administered alone (P < 0.0005). Our results are consistent with the hypothesis that both NEP and ACE contribute to the degradation of intravenously infused SP. ACE degradation of SP is sufficient to limit SP-induced bronchoconstriction even in the presence of specific NEP inhibition."} {"id": "PMID:1282125", "title": "Neuropeptide Y is a vasoconstrictor in human nasal mucosa.", "content": "Neuropeptide Y (NPY) is a neurotransmitter in sympathetic nerve fibers in human nasal mucosa. Like norepinephrine, NPY acts as a vasoconstrictor. An established method of nasal provocation was used to determine the effects of topically applied NPY on nasal resistance to airflow measured by anterior rhinomanometry, the protein content of nasal secretions, and the protein content of bradykinin-induced secretions. NPY (2.3 nmol) reduced the resistance to inspiratory airflow by 57 +/- 18% (P < 0.001) in 10 normal subjects and by 50 +/- 17% (P < 0.05) in 12 subjects with perennial rhinitis. In nasal provocations, NPY in doses of 0.1-10 nmol had no effect on vascular (albumin), glandular (lysozyme, glycoconjugate), or total proteins present in lavaged nasal secretions. Because the vasoconstrictor properties of NPY may only be apparent in the presence of increased vascular permeability and albumin exudation, bradykinin (BK) nasal provocation was performed. BK (500 nmol) significantly increase total protein (10- to 20-fold), albumin (10- to 30-fold), and glycoconjugate (2- to 5-fold) in lavage fluid. NPY (2.3 nmol) reduced BK-induced total protein by 59 +/- 15% (P < 0.05) and albumin by 63 +/- 17% (P < 0.02) but had no significant effect on glandular secretion. Therefore exogenous administration of NPY to the human nasal mucosa reduced nasal airflow resistance and albumin exudation without affecting submucosal gland secretion. NPY agonists may be useful for the treatment of mucosal diseases characterized by vasodilation, vascular permeability, and plasma exudation.", "contents": "Neuropeptide Y is a vasoconstrictor in human nasal mucosa. Neuropeptide Y (NPY) is a neurotransmitter in sympathetic nerve fibers in human nasal mucosa. Like norepinephrine, NPY acts as a vasoconstrictor. An established method of nasal provocation was used to determine the effects of topically applied NPY on nasal resistance to airflow measured by anterior rhinomanometry, the protein content of nasal secretions, and the protein content of bradykinin-induced secretions. NPY (2.3 nmol) reduced the resistance to inspiratory airflow by 57 +/- 18% (P < 0.001) in 10 normal subjects and by 50 +/- 17% (P < 0.05) in 12 subjects with perennial rhinitis. In nasal provocations, NPY in doses of 0.1-10 nmol had no effect on vascular (albumin), glandular (lysozyme, glycoconjugate), or total proteins present in lavaged nasal secretions. Because the vasoconstrictor properties of NPY may only be apparent in the presence of increased vascular permeability and albumin exudation, bradykinin (BK) nasal provocation was performed. BK (500 nmol) significantly increase total protein (10- to 20-fold), albumin (10- to 30-fold), and glycoconjugate (2- to 5-fold) in lavage fluid. NPY (2.3 nmol) reduced BK-induced total protein by 59 +/- 15% (P < 0.05) and albumin by 63 +/- 17% (P < 0.02) but had no significant effect on glandular secretion. Therefore exogenous administration of NPY to the human nasal mucosa reduced nasal airflow resistance and albumin exudation without affecting submucosal gland secretion. NPY agonists may be useful for the treatment of mucosal diseases characterized by vasodilation, vascular permeability, and plasma exudation."} {"id": "PMID:1282126", "title": "Novel myosin isoform in nuclear chain fibers of rat muscle spindles produced in response to endurance swimming.", "content": "With the use of myosin adenosinetriphosphatase (ATPase) and immunofluorescence staining methods, the adaptive responses of intrafusal and extrafusal fibers to endurance swimming were studied in frozen sections of rat soleus (SOL) and extensor digitorum longus (EDL) muscles. Glycogen depletion confirmed muscle fatigue at the end of a standardized bout of exercise. No significant age-dependent changes in myosin isoforms were detected in any fibers. The 12-wk training increased type I fibers by 10.9% in the SOL and type IIa fibers in the EDL by 16.6%. In trained muscle sections, both staining methods identified a permuted chain fiber, expressed the same as the myosin isoform in the bag2 fiber. However, no exercise-induced change of myosin isoform profile was found in the bag1 and bag2 fibers. Myosin ATPase (and immunofluorescence) staining showed the percentage of permuted chain fibers increased from 0 to 6.7% (5.6%) after 6 wk of training and to 19.2% (14.1%) after 12 wk of training and that it was still at 6.1% (4.2%) 10 wks after training. A novel myosin isoform may thus be expressed in nuclear chain fibers by repetitive recruitment of muscle spindles.", "contents": "Novel myosin isoform in nuclear chain fibers of rat muscle spindles produced in response to endurance swimming. With the use of myosin adenosinetriphosphatase (ATPase) and immunofluorescence staining methods, the adaptive responses of intrafusal and extrafusal fibers to endurance swimming were studied in frozen sections of rat soleus (SOL) and extensor digitorum longus (EDL) muscles. Glycogen depletion confirmed muscle fatigue at the end of a standardized bout of exercise. No significant age-dependent changes in myosin isoforms were detected in any fibers. The 12-wk training increased type I fibers by 10.9% in the SOL and type IIa fibers in the EDL by 16.6%. In trained muscle sections, both staining methods identified a permuted chain fiber, expressed the same as the myosin isoform in the bag2 fiber. However, no exercise-induced change of myosin isoform profile was found in the bag1 and bag2 fibers. Myosin ATPase (and immunofluorescence) staining showed the percentage of permuted chain fibers increased from 0 to 6.7% (5.6%) after 6 wk of training and to 19.2% (14.1%) after 12 wk of training and that it was still at 6.1% (4.2%) 10 wks after training. A novel myosin isoform may thus be expressed in nuclear chain fibers by repetitive recruitment of muscle spindles."} {"id": "PMID:1282127", "title": "Changes in airway reactivity to exogenous and endogenous acetylcholine and substance P after anaphylactic bronchoconstriction in anaesthetized guinea-pigs.", "content": "1. In anaesthetized, actively sensitized guinea-pigs, the anaphylactic shock induced by antigen aerosol challenge (5 s; 50 mg ml-1) was followed by increase in airway reactivity to both acetylcholine and substance P. In particular dose-response curves to acetylcholine (3-1000 micrograms kg-1 i.v.) and to substance P (5-80 micrograms kg-1 i.v.) obtained in antigen exposed animals were significantly shifted to the left of those performed in control guinea-pigs (exposed to saline aerosol). 2. The hyperreactive phenomenon after antigen aerosol was also evident when capsaicin-induced bronchoconstriction (1-4 micrograms kg-1 i.v.) was tested; the degree of hyperresponsiveness was similar to that observed with acetylcholine and substance P as agonists. 3. The frequency-response curves to vagal stimulation, either cholinergic or NANC in nature, were not significantly modified in guinea-pigs challenged with the antigen in respect to those aerosolized with saline. 4. The data obtained in the present study indicate that the airway hyperresponsiveness present in the animal model used is non-specific, involving both cholinergic and peptidergic effects. On the other hand, the lack of potentiation of the bronchoconstriction response to electrical stimulation might suggest that the establishment of a clear hyperreactive phenomenon is under the control of different mechanisms unrelated to increased bronchial reactivity.", "contents": "Changes in airway reactivity to exogenous and endogenous acetylcholine and substance P after anaphylactic bronchoconstriction in anaesthetized guinea-pigs. 1. In anaesthetized, actively sensitized guinea-pigs, the anaphylactic shock induced by antigen aerosol challenge (5 s; 50 mg ml-1) was followed by increase in airway reactivity to both acetylcholine and substance P. In particular dose-response curves to acetylcholine (3-1000 micrograms kg-1 i.v.) and to substance P (5-80 micrograms kg-1 i.v.) obtained in antigen exposed animals were significantly shifted to the left of those performed in control guinea-pigs (exposed to saline aerosol). 2. The hyperreactive phenomenon after antigen aerosol was also evident when capsaicin-induced bronchoconstriction (1-4 micrograms kg-1 i.v.) was tested; the degree of hyperresponsiveness was similar to that observed with acetylcholine and substance P as agonists. 3. The frequency-response curves to vagal stimulation, either cholinergic or NANC in nature, were not significantly modified in guinea-pigs challenged with the antigen in respect to those aerosolized with saline. 4. The data obtained in the present study indicate that the airway hyperresponsiveness present in the animal model used is non-specific, involving both cholinergic and peptidergic effects. On the other hand, the lack of potentiation of the bronchoconstriction response to electrical stimulation might suggest that the establishment of a clear hyperreactive phenomenon is under the control of different mechanisms unrelated to increased bronchial reactivity."} {"id": "PMID:1282128", "title": "Interaction of U-50,488H with calcium channel agonists and antagonists in different cardiac tissues.", "content": "1. The present study examined the interaction of U-50,488H (specific k-agonist) with diltiazem (calcium channel antagonist) or Bay K 8644 (calcium channel agonist) on isolated left and right atria of the rat. 2. The inhibitory effects of U-50,488H on left and right atria were unaffected by the k-receptor antagonist MR-2266 (10(-7) and 5 x 10(-7) M) suggesting that they were not mediated via opioid receptors. 3. The inhibitory cardiac effects induced by U-50,488H were antagonized in presence of Bay K 8644. The negative inotropic response to the maximum concentration of U-50,488H used in presence of two concentrations of Bay K 8644 (10(-9), 3 x 10(-9) M) were 19 +/- 0.9% and 9 +/- 0.1% reductions in contractility respectively. These values were significantly (P < 0.001) lower than that obtained with the k-agonist alone (76 +/- 3.6%). Similar results were obtained for the negative chronotropism of right atria. 4. The inhibitory effect of U-50,488H was potentiating in the presence of diltiazem (5 x 10(-8) or 10(-7) M). The IC50 values for U-50,488H obtained in the left (22 +/- 2 x 10(-6) M) and right atria (610 +/- 40 x 10(-6) M) were significantly (P < 0.001) decreased in the presence of diltiazem. 5. These data demonstrate that transmembrane calcium influx may play an important role in the inhibitory cardiac effects of U-50,488H, which may be independent of k-receptor stimulation.", "contents": "Interaction of U-50,488H with calcium channel agonists and antagonists in different cardiac tissues. 1. The present study examined the interaction of U-50,488H (specific k-agonist) with diltiazem (calcium channel antagonist) or Bay K 8644 (calcium channel agonist) on isolated left and right atria of the rat. 2. The inhibitory effects of U-50,488H on left and right atria were unaffected by the k-receptor antagonist MR-2266 (10(-7) and 5 x 10(-7) M) suggesting that they were not mediated via opioid receptors. 3. The inhibitory cardiac effects induced by U-50,488H were antagonized in presence of Bay K 8644. The negative inotropic response to the maximum concentration of U-50,488H used in presence of two concentrations of Bay K 8644 (10(-9), 3 x 10(-9) M) were 19 +/- 0.9% and 9 +/- 0.1% reductions in contractility respectively. These values were significantly (P < 0.001) lower than that obtained with the k-agonist alone (76 +/- 3.6%). Similar results were obtained for the negative chronotropism of right atria. 4. The inhibitory effect of U-50,488H was potentiating in the presence of diltiazem (5 x 10(-8) or 10(-7) M). The IC50 values for U-50,488H obtained in the left (22 +/- 2 x 10(-6) M) and right atria (610 +/- 40 x 10(-6) M) were significantly (P < 0.001) decreased in the presence of diltiazem. 5. These data demonstrate that transmembrane calcium influx may play an important role in the inhibitory cardiac effects of U-50,488H, which may be independent of k-receptor stimulation."} {"id": "PMID:1282129", "title": "Anomalous reversed-phase high-performance liquid chromatographic behavior of synthetic peptides related to antigenic helper T cell sites.", "content": "Sets of overlapping synthetic peptides for three well characterized proteins (sperm whale myoglobin, hen egg lysozyme, and the circumsporozoite protein from Plasmodium falciparum) were prepared and examined by reversed-phase high-performance liquid chromatography (RP-HPLC). Using retention coefficients to predict the retention time of each peptide, several peptides in each protein set were found that exhibited anomalous behavior (i.e. eluted significantly later than predicted). Previous work with model peptides has shown that this anomalous behavior can be attributed to specific amphipathic arrangements induced by the lipid stationary phase during the RP-HPLC process. In the current study it was found that although not all of the peptides containing an antigenic T cell site displayed anomalously late behavior, all of the peptides which eluted anomalously late during RP-HPLC included the regions of these proteins known from earlier studies to be antigenic T cell sites.", "contents": "Anomalous reversed-phase high-performance liquid chromatographic behavior of synthetic peptides related to antigenic helper T cell sites. Sets of overlapping synthetic peptides for three well characterized proteins (sperm whale myoglobin, hen egg lysozyme, and the circumsporozoite protein from Plasmodium falciparum) were prepared and examined by reversed-phase high-performance liquid chromatography (RP-HPLC). Using retention coefficients to predict the retention time of each peptide, several peptides in each protein set were found that exhibited anomalous behavior (i.e. eluted significantly later than predicted). Previous work with model peptides has shown that this anomalous behavior can be attributed to specific amphipathic arrangements induced by the lipid stationary phase during the RP-HPLC process. In the current study it was found that although not all of the peptides containing an antigenic T cell site displayed anomalously late behavior, all of the peptides which eluted anomalously late during RP-HPLC included the regions of these proteins known from earlier studies to be antigenic T cell sites."} {"id": "PMID:1282130", "title": "A comparison between one first generation and three second generation anti-HCV ELISAs: an investigation in high- and low-risk subjects in correlation with recombinant immunoblot assay and polymerase chain reaction.", "content": "One first generation assay (manufactured by Ortho, test I) and 3 second generation anti-HCV ELISAs (manufactured by Ortho, Abbott, and UBI, tests II-IV) were compared. Sera from 4 different sources were used: (1) intravenous drug-users (IVDUs, n = 50), (2) blood donors (n = 1055), (3) all clinical samples from one day of routine anti-HCV testing (n = 89), (4) hemodialysis patients previously found negative by test I but clinically suspected to have a HCV infection (n = 11). Confirmatory anti-HCV tests were carried out with a second generation recombinant immunoblot assay (RIBA II). In sera positive exclusively by test IV, one antibody consumption test (UBI HCV Neutralization EIA) and one further immunoblot assay (INNO-LIA HCV Ab) were used. PCR for HCV RNA was carried out on all hemodialysis patient sera and in the RIBA II positive blood donor sera. The second generation ELISAs discriminated 11 more positive samples than the first generation test (2 IVDUs, 5 blood donors, 4 clinical samples). The 9 sera from blood donors and clinical samples were all RIBA II positive or indeterminate. The second generation tests thus showed increased sensitivity. The second generation tests also showed increased specificity in that 4 samples that were positive by test I but negative by the second generation tests, were also negative by RIBA II. With few exceptions, all RIBA II-positive and most of the indeterminate samples were positive by the second generation ELISAs. With few exceptions, all the RIBA II-negative samples were negative by the second generation ELISAs. Eleven blood donor sera were positive by test IV exclusively where RIBA II and other supplementary assays were negative. The recently introduced second generation anti-HCV ELISAs were found to have a higher sensitivity than the first generation test. The tests also showed a good concordance with the exception of test IV in the group of blood donor sera.", "contents": "A comparison between one first generation and three second generation anti-HCV ELISAs: an investigation in high- and low-risk subjects in correlation with recombinant immunoblot assay and polymerase chain reaction. One first generation assay (manufactured by Ortho, test I) and 3 second generation anti-HCV ELISAs (manufactured by Ortho, Abbott, and UBI, tests II-IV) were compared. Sera from 4 different sources were used: (1) intravenous drug-users (IVDUs, n = 50), (2) blood donors (n = 1055), (3) all clinical samples from one day of routine anti-HCV testing (n = 89), (4) hemodialysis patients previously found negative by test I but clinically suspected to have a HCV infection (n = 11). Confirmatory anti-HCV tests were carried out with a second generation recombinant immunoblot assay (RIBA II). In sera positive exclusively by test IV, one antibody consumption test (UBI HCV Neutralization EIA) and one further immunoblot assay (INNO-LIA HCV Ab) were used. PCR for HCV RNA was carried out on all hemodialysis patient sera and in the RIBA II positive blood donor sera. The second generation ELISAs discriminated 11 more positive samples than the first generation test (2 IVDUs, 5 blood donors, 4 clinical samples). The 9 sera from blood donors and clinical samples were all RIBA II positive or indeterminate. The second generation tests thus showed increased sensitivity. The second generation tests also showed increased specificity in that 4 samples that were positive by test I but negative by the second generation tests, were also negative by RIBA II. With few exceptions, all RIBA II-positive and most of the indeterminate samples were positive by the second generation ELISAs. With few exceptions, all the RIBA II-negative samples were negative by the second generation ELISAs. Eleven blood donor sera were positive by test IV exclusively where RIBA II and other supplementary assays were negative. The recently introduced second generation anti-HCV ELISAs were found to have a higher sensitivity than the first generation test. The tests also showed a good concordance with the exception of test IV in the group of blood donor sera."} {"id": "PMID:1282131", "title": "A quantitative reverse transcriptase-polymerase chain reaction for HIV-1-specific RNA species.", "content": "The ability to evaluate the patterns and levels of human immunodeficiency virus type I (HIV-1)-specific RNA in latently and productively-infected cell lines, and primary human cells, is critical to the understanding of HIV-1 expression in cell cultures and possibly in vivo. We have developed a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), utilizing in vitro transcribed RNA standards, to evaluate the copy number per cell and per microgram of total cellular RNA of multiply-spliced, unspliced and total HIV-1-specific RNA species. The latently-infected monocytic and T-lymphocyte cell lines, U1 and ACH-2 respectively, are shown to express between 10(4) to 10(6) copies of total HIV-1-specific RNA per cell, based on the state of cellular stimulation. A dramatic increase of unspliced HIV-1-specific RNA in both the U1 cell line and the ACH-2 cell line is demonstrated by this quantitative RT-PCR, 24 h after stimulation with phorbol esters. These data suggest that a single integrated HIV-1 provirus can rapidly express large quantities of HIV-1-specific RNA. Quantitative RT-PCR, for HIV-1-specific transcripts, should prove extremely useful in evaluating retroviral load and pathogenesis in cell cultures and in vivo.", "contents": "A quantitative reverse transcriptase-polymerase chain reaction for HIV-1-specific RNA species. The ability to evaluate the patterns and levels of human immunodeficiency virus type I (HIV-1)-specific RNA in latently and productively-infected cell lines, and primary human cells, is critical to the understanding of HIV-1 expression in cell cultures and possibly in vivo. We have developed a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), utilizing in vitro transcribed RNA standards, to evaluate the copy number per cell and per microgram of total cellular RNA of multiply-spliced, unspliced and total HIV-1-specific RNA species. The latently-infected monocytic and T-lymphocyte cell lines, U1 and ACH-2 respectively, are shown to express between 10(4) to 10(6) copies of total HIV-1-specific RNA per cell, based on the state of cellular stimulation. A dramatic increase of unspliced HIV-1-specific RNA in both the U1 cell line and the ACH-2 cell line is demonstrated by this quantitative RT-PCR, 24 h after stimulation with phorbol esters. These data suggest that a single integrated HIV-1 provirus can rapidly express large quantities of HIV-1-specific RNA. Quantitative RT-PCR, for HIV-1-specific transcripts, should prove extremely useful in evaluating retroviral load and pathogenesis in cell cultures and in vivo."} {"id": "PMID:1282132", "title": "A new method for measuring reverse transcriptase activity by ELISA.", "content": "A new and sensitive assay of reverse transcriptase (RT) activity of retroviruses measures the incorporation of digoxigenin-labelled dUTP in newly synthesized DNA instead of radioactively labelled (3H- or 32P-)dTTP. To avoid difficulties associated with separation of non-incorporated nucleotides from the newly synthesized DNA, biotin-labelled dUTP is added to the reaction mixture in very low concentrations. After reverse transcription, the newly synthesized, doubly labelled DNA is immobilized on streptavidin-coated ELISA wells and evaluated photometrically by binding of peroxidase-conjugated anti-digoxigenin-antibodies (sheep) and subsequent colour development with 2,2'-azino-di[3-ethylbenzthiazolin-sulfonate(6)] (ABTSR) as substrate. For better standardization, it is suggested that RT activity is given in units (one unit of RT is the amount of enzyme incorporating one nanomole of labelled dNTP in 10 min at 37 degrees C into an acid precipitable DNA) rather than in cpm (counts per minute). The method is specific and easy to perform.", "contents": "A new method for measuring reverse transcriptase activity by ELISA. A new and sensitive assay of reverse transcriptase (RT) activity of retroviruses measures the incorporation of digoxigenin-labelled dUTP in newly synthesized DNA instead of radioactively labelled (3H- or 32P-)dTTP. To avoid difficulties associated with separation of non-incorporated nucleotides from the newly synthesized DNA, biotin-labelled dUTP is added to the reaction mixture in very low concentrations. After reverse transcription, the newly synthesized, doubly labelled DNA is immobilized on streptavidin-coated ELISA wells and evaluated photometrically by binding of peroxidase-conjugated anti-digoxigenin-antibodies (sheep) and subsequent colour development with 2,2'-azino-di[3-ethylbenzthiazolin-sulfonate(6)] (ABTSR) as substrate. For better standardization, it is suggested that RT activity is given in units (one unit of RT is the amount of enzyme incorporating one nanomole of labelled dNTP in 10 min at 37 degrees C into an acid precipitable DNA) rather than in cpm (counts per minute). The method is specific and easy to perform."} {"id": "PMID:1282133", "title": "Trichogerminoma. Report of 14 cases.", "content": "We report 14 cases of trichogerminoma, a rare form of cutaneous adnexal neoplasm, derived from hair germ epithelium. The neoplasms occurred in 9 men and 5 women. Their ages ranged from 16 to 73 years (median 53 years). The tumors were slow growing, asymptomatic dermal or subcutaneous nodules, located on the head and neck (6), trunk (4), extremities (2) and hip (1), with no distinguishing clinical features. Histologically, trichogerminomas were characterized by sharply circumscribed, pseudoencapsulated dermal and subcutaneous nodules, ranging in size from 0.4 to 4.0 cm in diameter (mean 1.9 cm). The nodules were subdivided into lobules separated by variable amounts of stroma that demonstrated varying cellularity and mucin content. The lobules were composed of basaloid cells that formed densely packed, round nests or \"cell balls\" resembling hair bulbs. The basaloid cells demonstrated peripheral palisading, keratinization and differentiation towards various pilosebaceous structures. Retraction spaces, well developed hair follicles and hair shafts were not observed. These distinctive histologic features separated these neoplasms from other tumors of pilar origin and from basal cell carcinoma. The trichogerminomas behaved in a benign fashion with one exception. Complete excision of the lesions is the treatment of choice.", "contents": "Trichogerminoma. Report of 14 cases. We report 14 cases of trichogerminoma, a rare form of cutaneous adnexal neoplasm, derived from hair germ epithelium. The neoplasms occurred in 9 men and 5 women. Their ages ranged from 16 to 73 years (median 53 years). The tumors were slow growing, asymptomatic dermal or subcutaneous nodules, located on the head and neck (6), trunk (4), extremities (2) and hip (1), with no distinguishing clinical features. Histologically, trichogerminomas were characterized by sharply circumscribed, pseudoencapsulated dermal and subcutaneous nodules, ranging in size from 0.4 to 4.0 cm in diameter (mean 1.9 cm). The nodules were subdivided into lobules separated by variable amounts of stroma that demonstrated varying cellularity and mucin content. The lobules were composed of basaloid cells that formed densely packed, round nests or \"cell balls\" resembling hair bulbs. The basaloid cells demonstrated peripheral palisading, keratinization and differentiation towards various pilosebaceous structures. Retraction spaces, well developed hair follicles and hair shafts were not observed. These distinctive histologic features separated these neoplasms from other tumors of pilar origin and from basal cell carcinoma. The trichogerminomas behaved in a benign fashion with one exception. Complete excision of the lesions is the treatment of choice."} {"id": "PMID:1282134", "title": "Mast cell quantitation by image analysis in adult mastocytosis and inflammatory skin disorders.", "content": "Mast cell numbers were quantitated in adult cases of mastocytosis demonstrating non-diffuse perivascular and upper dermal concentrations of mast cells. Using the Leder stain and computerised video image analysis, a mean of 382 (+/- 28 SE) mast cell per mm2 were counted in the superficial dermis in skin biopsies from 30 adult cases of mastocytosis, in contrast to a mean of 43 (+/- 5 SE) mast cells per mm2 in skin biopsies from 50 inflammatory dermatoses represented by subacute dermatitis, pigmented purpuric dermatosis, erythema multiforme, lichen planus and granuloma annulare. Ten skin biopsies showing no significant inflammation had a mean of 54 (+/- 7 SE) mast cells per mm2 in the upper dermis. The mean area of individual mast cells as assessed by image analysis in the mastocytosis group was 47.40 microns 2 (+/- 2.26 microns 2, SE) which was significantly different (P < 0.01) than the mast cell area (32.34 microns 2 +/- 2.22 microns 2, SE) in all other groups combined. Computerised video image analysis represents an alternative technique which is useful in assessing mast cell numbers and particularly mast cell size in adult cases of macular mastocytosis and in other dermatoses.", "contents": "Mast cell quantitation by image analysis in adult mastocytosis and inflammatory skin disorders. Mast cell numbers were quantitated in adult cases of mastocytosis demonstrating non-diffuse perivascular and upper dermal concentrations of mast cells. Using the Leder stain and computerised video image analysis, a mean of 382 (+/- 28 SE) mast cell per mm2 were counted in the superficial dermis in skin biopsies from 30 adult cases of mastocytosis, in contrast to a mean of 43 (+/- 5 SE) mast cells per mm2 in skin biopsies from 50 inflammatory dermatoses represented by subacute dermatitis, pigmented purpuric dermatosis, erythema multiforme, lichen planus and granuloma annulare. Ten skin biopsies showing no significant inflammation had a mean of 54 (+/- 7 SE) mast cells per mm2 in the upper dermis. The mean area of individual mast cells as assessed by image analysis in the mastocytosis group was 47.40 microns 2 (+/- 2.26 microns 2, SE) which was significantly different (P < 0.01) than the mast cell area (32.34 microns 2 +/- 2.22 microns 2, SE) in all other groups combined. Computerised video image analysis represents an alternative technique which is useful in assessing mast cell numbers and particularly mast cell size in adult cases of macular mastocytosis and in other dermatoses."} {"id": "PMID:1282135", "title": "Oral submucosal dendrocytes: factor XIIIa+ and CD34+ dendritic cell populations in normal tissue and fibrovascular lesions.", "content": "Factor XIIIa+ and CD34+ dendritic cells, believed to be subsets of monocyte/macrophages, have been identified in dermis and in dermal tumors. The purpose of this study was to determine the presence and distribution of analogous cell types in oral submucosa and oral fibro-vascular lesions. Antibodies to XIIIa, CD34, S-100 protein, and macrophage antigen (MAC 387) were tested on formalin-fixed, paraffin-embedded tissue sections from normal mucosa, peripheral fibroma (PF), peripheral ossifying fibroma (POF), peripheral giant cell granuloma (PGCG), pyogenic granuloma (PG), lymphangioma (La), benign fibrous histiocytoma (BFH), idiopathic histiocytosis (IH), angiofibroma (Af) using an ABC immunoperoxidase technique. Numbers of positively stained cells were compared to unstained cells in the tumors. XIIIa positive submucosal dendrocytes (CD34-, S-100-, MAC 387-) were found in abundance in normal tissue in characteristic distributions: collagen-associated, vessel-associated, and lymphoid-associated. The percentage of XIIIa+ cells in the oral tumors was as follows: PF: 10-30%, POF: 5-10%, PGCG: 0-5%, PG: 5-20%, La: 0%, BFH: 5-25%, IH: 0%, and Af: 10-20%. CD34+ dendrocytes (XIIIa-, S-100-, MAC 387-) were few in number and were found in deeper submucosa, especially around skeletal muscle. Other than blood vascular endothelium, CD34+ cells were not generally seen in the oral tumors studied. It is concluded that two previously unrecognized dendrocyte populations reside in normal submucosa. XIIIa+ cells participate in the formation of some oral reactive and neoplastic lesions.", "contents": "Oral submucosal dendrocytes: factor XIIIa+ and CD34+ dendritic cell populations in normal tissue and fibrovascular lesions. Factor XIIIa+ and CD34+ dendritic cells, believed to be subsets of monocyte/macrophages, have been identified in dermis and in dermal tumors. The purpose of this study was to determine the presence and distribution of analogous cell types in oral submucosa and oral fibro-vascular lesions. Antibodies to XIIIa, CD34, S-100 protein, and macrophage antigen (MAC 387) were tested on formalin-fixed, paraffin-embedded tissue sections from normal mucosa, peripheral fibroma (PF), peripheral ossifying fibroma (POF), peripheral giant cell granuloma (PGCG), pyogenic granuloma (PG), lymphangioma (La), benign fibrous histiocytoma (BFH), idiopathic histiocytosis (IH), angiofibroma (Af) using an ABC immunoperoxidase technique. Numbers of positively stained cells were compared to unstained cells in the tumors. XIIIa positive submucosal dendrocytes (CD34-, S-100-, MAC 387-) were found in abundance in normal tissue in characteristic distributions: collagen-associated, vessel-associated, and lymphoid-associated. The percentage of XIIIa+ cells in the oral tumors was as follows: PF: 10-30%, POF: 5-10%, PGCG: 0-5%, PG: 5-20%, La: 0%, BFH: 5-25%, IH: 0%, and Af: 10-20%. CD34+ dendrocytes (XIIIa-, S-100-, MAC 387-) were few in number and were found in deeper submucosa, especially around skeletal muscle. Other than blood vascular endothelium, CD34+ cells were not generally seen in the oral tumors studied. It is concluded that two previously unrecognized dendrocyte populations reside in normal submucosa. XIIIa+ cells participate in the formation of some oral reactive and neoplastic lesions."} {"id": "PMID:1282136", "title": "Monoclonal antibody analysis of keratin expression in carcinomas of sweat glands.", "content": "Characteristics of keratins of five carcinomas of sweat gland origin were immunohistochemically investigated with several antikeratin monoclonal antibodies with differing specificities. Specimens were obtained from two cases of mucinous carcinoma of the skin, two cases of classic type of eccrine adenocarcinoma, and a case of eccrine porocarcinoma. The tumor cells of mucinous carcinoma expressed only simple epithelial keratins. In a case of eccrine adenocarcinoma, simple epithelial keratin 19 was diffusely expressed. The expression of the other simple epithelial keratins was confined to the luminal cells, whereas the remaining tumor cells further expressed stratified epithelial keratins. Eccrine porocarcinoma and a second case of eccrine adenocarcinoma did not express simple epithelial keratins, although stratified epithelial keratins were diffusely expressed. These data suggest that carcinomas of sweat glands express various combinations of simple and stratified epithelial keratins. Development of additional data along these lines may help to further define their classification.", "contents": "Monoclonal antibody analysis of keratin expression in carcinomas of sweat glands. Characteristics of keratins of five carcinomas of sweat gland origin were immunohistochemically investigated with several antikeratin monoclonal antibodies with differing specificities. Specimens were obtained from two cases of mucinous carcinoma of the skin, two cases of classic type of eccrine adenocarcinoma, and a case of eccrine porocarcinoma. The tumor cells of mucinous carcinoma expressed only simple epithelial keratins. In a case of eccrine adenocarcinoma, simple epithelial keratin 19 was diffusely expressed. The expression of the other simple epithelial keratins was confined to the luminal cells, whereas the remaining tumor cells further expressed stratified epithelial keratins. Eccrine porocarcinoma and a second case of eccrine adenocarcinoma did not express simple epithelial keratins, although stratified epithelial keratins were diffusely expressed. These data suggest that carcinomas of sweat glands express various combinations of simple and stratified epithelial keratins. Development of additional data along these lines may help to further define their classification."} {"id": "PMID:1282137", "title": "Simple epithelial cytokeratin-expression in seborrheic keratosis.", "content": "The cytokeratin expression of seborrheic keratosis was studied by means of immunohistochemistry and compared with that of normal human skin. The following findings were obtained in seborrheic keratosis: (1) a partial lack of high molecular weight cytokeratin (#1/68 kD, #10/56.6 kD) in all ten cases examined; (2) the detection of cytokeratin typical for simple epithelia (#8/52.5 kD, #18/45 kD, #19/40 kD) in eight of ten cases; and (3) the detection of cytokeratin #5/58 kD in suprabasal cells in 5 of 10 cases. An immunoelectron-microscopic investigation, using an anti-keratin antibody against cytokeratin #19/40 kD, revealed a whirl-like arrangement of keratin filaments within immunoreactive cells, in contrast to a linear, parallel arrangement in non-immunoreactive cells. Cells known to express cytokeratin typical for simple epithelia, such as sweat gland cells or Merkel cells, were not observed. The altered cytokeratin gene-expression in seborrheic keratosis may be attributable to de-differentiation of tumor cells or potential re-differentiation towards embryonic keratinocytes.", "contents": "Simple epithelial cytokeratin-expression in seborrheic keratosis. The cytokeratin expression of seborrheic keratosis was studied by means of immunohistochemistry and compared with that of normal human skin. The following findings were obtained in seborrheic keratosis: (1) a partial lack of high molecular weight cytokeratin (#1/68 kD, #10/56.6 kD) in all ten cases examined; (2) the detection of cytokeratin typical for simple epithelia (#8/52.5 kD, #18/45 kD, #19/40 kD) in eight of ten cases; and (3) the detection of cytokeratin #5/58 kD in suprabasal cells in 5 of 10 cases. An immunoelectron-microscopic investigation, using an anti-keratin antibody against cytokeratin #19/40 kD, revealed a whirl-like arrangement of keratin filaments within immunoreactive cells, in contrast to a linear, parallel arrangement in non-immunoreactive cells. Cells known to express cytokeratin typical for simple epithelia, such as sweat gland cells or Merkel cells, were not observed. The altered cytokeratin gene-expression in seborrheic keratosis may be attributable to de-differentiation of tumor cells or potential re-differentiation towards embryonic keratinocytes."} {"id": "PMID:1282138", "title": "Removal of monocytes from cell suspensions with anti-CD14 antibody and carbonyl-iron, using Fc gamma R-dependent accessory function as a sensitive measure of monocyte presence.", "content": "Human (Fc gamma RI-positive) monocytes are required as accessory cells when T cell proliferation is induced by murine IgG2a anti-CD3 monoclonal antibodies (mAbs). This T cell proliferation assay provides a sensitive method for detecting the presence of monocytes (less than 1% of monocytes can be detected), and we have used it to monitor the effectiveness of different procedures for the removal of monocytes from peripheral blood mononuclear cells. Counterflow centrifugation, phagocytosis of carbonyl-iron, adherence to plastic, monocyte depletion with magnetic beads (Dynabeads M450), and panning with anti-CD14 antibodies each strongly reduced the number of monocytes. However, none of these methods, when used on their own, were capable of completely abolishing the mitogenic response to murine IgG2a anti-CD3 mAb. A virtually complete depletion of monocytes was obtained when the panning procedure using anti-CD14 antibodies was combined with phagocytosis of carbonyl-iron. Importantly, this method could also be used with cryopreserved cells. We have applied this improved method for the removal of monocytes, to study T cell proliferation induced by murine IgG2b anti-CD3 mAb. We were able to demonstrate with this model that cells other than monocytes were able to provide accessory function.", "contents": "Removal of monocytes from cell suspensions with anti-CD14 antibody and carbonyl-iron, using Fc gamma R-dependent accessory function as a sensitive measure of monocyte presence. Human (Fc gamma RI-positive) monocytes are required as accessory cells when T cell proliferation is induced by murine IgG2a anti-CD3 monoclonal antibodies (mAbs). This T cell proliferation assay provides a sensitive method for detecting the presence of monocytes (less than 1% of monocytes can be detected), and we have used it to monitor the effectiveness of different procedures for the removal of monocytes from peripheral blood mononuclear cells. Counterflow centrifugation, phagocytosis of carbonyl-iron, adherence to plastic, monocyte depletion with magnetic beads (Dynabeads M450), and panning with anti-CD14 antibodies each strongly reduced the number of monocytes. However, none of these methods, when used on their own, were capable of completely abolishing the mitogenic response to murine IgG2a anti-CD3 mAb. A virtually complete depletion of monocytes was obtained when the panning procedure using anti-CD14 antibodies was combined with phagocytosis of carbonyl-iron. Importantly, this method could also be used with cryopreserved cells. We have applied this improved method for the removal of monocytes, to study T cell proliferation induced by murine IgG2b anti-CD3 mAb. We were able to demonstrate with this model that cells other than monocytes were able to provide accessory function."} {"id": "PMID:1282139", "title": "Immunodetection of recombinant proteins based on antibodies directed against a metal binding peptide engineered for purification by immobilized metal affinity chromatography.", "content": "Recently we reported (Evans, D.B., Tarpley W.G. and Sharma, S.K. (1991) Expression and characterization of chimeric rDNA proteins engineered for purification and cleavage. Protein Expr. Purif. 2, 205-213) a genetically engineered metal binding peptide (mbp) for the purification of recombinant proteins by immobilized metal affinity chromatography (IMAC). Therefore, we have been interested in developing mbp-based immunodetection methods for these engineered proteins. To this end, the following linker peptide containing the mbp (His-Asp-His-Asp-His) was designed, synthesized and conjugated to porcine thyroglobulin: Ac-Cys-Gly-Glu-Glu-His-Asp-His-Asp-His-Pro-Phe-His-Leu. Rabbits immunized with this conjugate developed antibodies that cross-react with peptides containing the mbp sequence. A number of chimeric recombinant proteins, expressed in E. coli, with and without the mbp portion (His-Asp-His-Asp-His) of the fusion peptide (His-Asp-His-Asp-His-Pro-Phe-His-Leu) were analyzed by ELISA and immunoblotting. Results from these studies show that the anti-mbp antibodies detect chimeric proteins containing the mbp, while chimeric proteins lacking this pentapeptide were negative in both immunodetection techniques. The usefulness of this approach has also been demonstrated in following IMAC purification and enzymatic cleavage of the mbp. These immunodetection techniques utilizing anti-mbp antibodies should be applicable to other proteins engineered to contain the mbp for IMAC purification.", "contents": "Immunodetection of recombinant proteins based on antibodies directed against a metal binding peptide engineered for purification by immobilized metal affinity chromatography. Recently we reported (Evans, D.B., Tarpley W.G. and Sharma, S.K. (1991) Expression and characterization of chimeric rDNA proteins engineered for purification and cleavage. Protein Expr. Purif. 2, 205-213) a genetically engineered metal binding peptide (mbp) for the purification of recombinant proteins by immobilized metal affinity chromatography (IMAC). Therefore, we have been interested in developing mbp-based immunodetection methods for these engineered proteins. To this end, the following linker peptide containing the mbp (His-Asp-His-Asp-His) was designed, synthesized and conjugated to porcine thyroglobulin: Ac-Cys-Gly-Glu-Glu-His-Asp-His-Asp-His-Pro-Phe-His-Leu. Rabbits immunized with this conjugate developed antibodies that cross-react with peptides containing the mbp sequence. A number of chimeric recombinant proteins, expressed in E. coli, with and without the mbp portion (His-Asp-His-Asp-His) of the fusion peptide (His-Asp-His-Asp-His-Pro-Phe-His-Leu) were analyzed by ELISA and immunoblotting. Results from these studies show that the anti-mbp antibodies detect chimeric proteins containing the mbp, while chimeric proteins lacking this pentapeptide were negative in both immunodetection techniques. The usefulness of this approach has also been demonstrated in following IMAC purification and enzymatic cleavage of the mbp. These immunodetection techniques utilizing anti-mbp antibodies should be applicable to other proteins engineered to contain the mbp for IMAC purification."} {"id": "PMID:1282140", "title": "Recognition of Mycobacterium leprae recombinant 18-kDa proteins in leprosy.", "content": "Three different, purified, Escherichia coli-derived, recombinant preparations of the Mycobacterium leprae 18K protein were compared for their immunological recognition in leprosy. The preparations tested were 18K fusion proteins containing 70% (amino acids 38-148) of the full 18K protein fused to either a short leader sequence containing six asparagine residues or to beta-galactosidase, and the full length 18K protein. All three recombinant antigens were recognized by IgG antibodies which were restricted mostly to lepromatous leprosy patients. The 18K antigen with the asparagine leader sequence showed better reactivity with IgG antibodies compared with the other two 18K preparations. In lymphocyte proliferation assays, the truncated 18K and the full-length 18K showed equivalent responses in the same donors with strongest recognition in donors who were also strongly responsive to the M. leprae soluble sonicate. These results indicate that the major human B- and T-cell epitopes are located within the segment 38-148, although some individuals may recognize additional epitopes at the NH2-terminal end.", "contents": "Recognition of Mycobacterium leprae recombinant 18-kDa proteins in leprosy. Three different, purified, Escherichia coli-derived, recombinant preparations of the Mycobacterium leprae 18K protein were compared for their immunological recognition in leprosy. The preparations tested were 18K fusion proteins containing 70% (amino acids 38-148) of the full 18K protein fused to either a short leader sequence containing six asparagine residues or to beta-galactosidase, and the full length 18K protein. All three recombinant antigens were recognized by IgG antibodies which were restricted mostly to lepromatous leprosy patients. The 18K antigen with the asparagine leader sequence showed better reactivity with IgG antibodies compared with the other two 18K preparations. In lymphocyte proliferation assays, the truncated 18K and the full-length 18K showed equivalent responses in the same donors with strongest recognition in donors who were also strongly responsive to the M. leprae soluble sonicate. These results indicate that the major human B- and T-cell epitopes are located within the segment 38-148, although some individuals may recognize additional epitopes at the NH2-terminal end."} {"id": "PMID:1282141", "title": "Comparison of bis-di-octadecylamide of trehalose dicarboxylic acid (BDA.TDA) with glycolipid SL-IV as ELISA antigens for the serodiagnosis of leprosy.", "content": "Two glycolipids--one synthetic and non-natural (BDA.TDA), the other natural and Mycobacterium tuberculosis species-specific (SL-IV)--were tested to determine their serological activity in sera obtained from leprosy patients, and to determine their discriminating ability in the detection of disease. The ELISA results obtained in the IgG antibody class show that both were useful substances capable of detecting multibacillary and paucibacillary disease in about 2 out of 3 leprosy patients. When these antigens were tested in parallel, the sensitivity of the ELISA test was increased by 10% without a decrease in specificity.", "contents": "Comparison of bis-di-octadecylamide of trehalose dicarboxylic acid (BDA.TDA) with glycolipid SL-IV as ELISA antigens for the serodiagnosis of leprosy. Two glycolipids--one synthetic and non-natural (BDA.TDA), the other natural and Mycobacterium tuberculosis species-specific (SL-IV)--were tested to determine their serological activity in sera obtained from leprosy patients, and to determine their discriminating ability in the detection of disease. The ELISA results obtained in the IgG antibody class show that both were useful substances capable of detecting multibacillary and paucibacillary disease in about 2 out of 3 leprosy patients. When these antigens were tested in parallel, the sensitivity of the ELISA test was increased by 10% without a decrease in specificity."} {"id": "PMID:1282142", "title": "Enzyme linked immunosorbent assay of a 12-kDa protein of Mycobacterium leprae with sera from leprosy patients.", "content": "A low molecular weight protein was obtained from a sonicate of armadillo-derived Mycobacterium leprae cells and from a lambda gt11 phage lysate of Escherichia coli (specifying the M. leprae 12-kDa protein) by a single step of ultrafiltration. Both proteins had an approximate molecular weight of about 12,000 (by SDS-PAGE) and were recognized by the M. leprae 12-kDa-specific monoclonal antibody ML06 by immunoblotting. Sera from 79 leprosy patients across the clinical spectrum, 17 contacts, and 12 normal healthy individuals were screened in an enzyme-linked immunosorbent assay (ELISA) using the 12-kDa proteins as the antigens. Antibodies to the 12-kDa protein (from lysate as well as sonicate) were detected in patients' sera across the clinical spectrum (44%-100% positivity), while no detectable reactivity was observed with control or contact sera. Sera from patients who had undergone a year or more of chemotherapy exhibited no reactivity compared to those from patients with only 3-6 months of chemotherapy. The 12-kDa proteins were also recognized by rabbit hyper-immune M. leprae antiserum.", "contents": "Enzyme linked immunosorbent assay of a 12-kDa protein of Mycobacterium leprae with sera from leprosy patients. A low molecular weight protein was obtained from a sonicate of armadillo-derived Mycobacterium leprae cells and from a lambda gt11 phage lysate of Escherichia coli (specifying the M. leprae 12-kDa protein) by a single step of ultrafiltration. Both proteins had an approximate molecular weight of about 12,000 (by SDS-PAGE) and were recognized by the M. leprae 12-kDa-specific monoclonal antibody ML06 by immunoblotting. Sera from 79 leprosy patients across the clinical spectrum, 17 contacts, and 12 normal healthy individuals were screened in an enzyme-linked immunosorbent assay (ELISA) using the 12-kDa proteins as the antigens. Antibodies to the 12-kDa protein (from lysate as well as sonicate) were detected in patients' sera across the clinical spectrum (44%-100% positivity), while no detectable reactivity was observed with control or contact sera. Sera from patients who had undergone a year or more of chemotherapy exhibited no reactivity compared to those from patients with only 3-6 months of chemotherapy. The 12-kDa proteins were also recognized by rabbit hyper-immune M. leprae antiserum."} {"id": "PMID:1282143", "title": "Analysis of circulating immune complexes from leprosy patients for Mycobacterium leprae antigens.", "content": "Circulating immune complexes (CICs) from 31 leprosy patients (16 tuberculoid, 15 lepromatous) and 12 healthy volunteers, precipitated by 3.5% polyethylene glycol, were individually subjected to SDS-PAGE and immunoblotting using a variety of monoclonal and polyclonal antibodies against Mycobacterium leprae. A common mycobacterial antigen of an apparent molecular size of 65 kDa was identified in CICs from about 40% of the patients. No correlation was observed between the positivity for this antigen and any of the following parameters: bacterial index, M. leprae-specific antibody titers, motor nerve involvement, duration of disease or treatment. Nevertheless, patients with a relatively recent and massive infection were more frequently positive for antigen than the others.", "contents": "Analysis of circulating immune complexes from leprosy patients for Mycobacterium leprae antigens. Circulating immune complexes (CICs) from 31 leprosy patients (16 tuberculoid, 15 lepromatous) and 12 healthy volunteers, precipitated by 3.5% polyethylene glycol, were individually subjected to SDS-PAGE and immunoblotting using a variety of monoclonal and polyclonal antibodies against Mycobacterium leprae. A common mycobacterial antigen of an apparent molecular size of 65 kDa was identified in CICs from about 40% of the patients. No correlation was observed between the positivity for this antigen and any of the following parameters: bacterial index, M. leprae-specific antibody titers, motor nerve involvement, duration of disease or treatment. Nevertheless, patients with a relatively recent and massive infection were more frequently positive for antigen than the others."} {"id": "PMID:1282144", "title": "Ionic selectivity of Ih channels of rod photoreceptors in tiger salamanders.", "content": "Ionic selectivity of Ih channels of tiger salamander rod photoreceptors was investigated using whole-cell voltage clamp. Measured reversal potentials and the Goldman-Hodgkin-Katz voltage equation were used to calculate permeability ratios with 20 mM K+ as a reference. In the absence of external K+, Ih is small and hard to discern. Hence, we defined Ih as the current blocked by 2 mM external Cs+. Some small amines permeate Ih channels, with the following permeability ratios (PX/PK):NH4+, 0.17; methylammonium, 0.06; and hydrazine, 0.04. Other amines are tially impermeant: dimethylammonium (< 0.02), ethylammonium (< 0.01), and tetramethylammonium (< 0.01). When K+ is the only external permeant ion and its concentration is varied, the reversal potential of Ih follows the Nernst potential for a K+ electrode. Ih channels are also permeable to other alkali metal cations (PX/PK): T1+, > 1.55; K+, 1; Rb+, > 0.55; Na+, 0.33; Li+, 0.02. Except for Na+, the relative slope conductance had a similar sequence (GX/GK): T1+, 1.07; K+, 1; Rb+, 0.37; NH4+, 0.07; Na+, 0.02. Based on permeabilities to organic cations, the narrowest part of the pore has a diameter between 4.0 and 4.6 A. Some permeant cations have large effects on the gating kinetics of Ih channels; however, permeant cations appear to have little effect on the steady-state activation curve of Ih channels. Lowering K+ or replacing K+ with Na+ reduces the maximal conductance of Ih but does not shift or change the steepness of its voltage dependence. With ammonium or methylammonium replacing K+ a similar pattern is seen, except that there is a small positive shift of approximately 10 mV in the voltage dependence.", "contents": "Ionic selectivity of Ih channels of rod photoreceptors in tiger salamanders. Ionic selectivity of Ih channels of tiger salamander rod photoreceptors was investigated using whole-cell voltage clamp. Measured reversal potentials and the Goldman-Hodgkin-Katz voltage equation were used to calculate permeability ratios with 20 mM K+ as a reference. In the absence of external K+, Ih is small and hard to discern. Hence, we defined Ih as the current blocked by 2 mM external Cs+. Some small amines permeate Ih channels, with the following permeability ratios (PX/PK):NH4+, 0.17; methylammonium, 0.06; and hydrazine, 0.04. Other amines are tially impermeant: dimethylammonium (< 0.02), ethylammonium (< 0.01), and tetramethylammonium (< 0.01). When K+ is the only external permeant ion and its concentration is varied, the reversal potential of Ih follows the Nernst potential for a K+ electrode. Ih channels are also permeable to other alkali metal cations (PX/PK): T1+, > 1.55; K+, 1; Rb+, > 0.55; Na+, 0.33; Li+, 0.02. Except for Na+, the relative slope conductance had a similar sequence (GX/GK): T1+, 1.07; K+, 1; Rb+, 0.37; NH4+, 0.07; Na+, 0.02. Based on permeabilities to organic cations, the narrowest part of the pore has a diameter between 4.0 and 4.6 A. Some permeant cations have large effects on the gating kinetics of Ih channels; however, permeant cations appear to have little effect on the steady-state activation curve of Ih channels. Lowering K+ or replacing K+ with Na+ reduces the maximal conductance of Ih but does not shift or change the steepness of its voltage dependence. With ammonium or methylammonium replacing K+ a similar pattern is seen, except that there is a small positive shift of approximately 10 mV in the voltage dependence."} {"id": "PMID:1282145", "title": "Block of the cyclic GMP-gated channel of vertebrate rod and cone photoreceptors by l-cis-diltiazem.", "content": "Inside-out patches were excised from catfish rod or cone outer segments. Single channel and macroscopic currents were recorded from GMP-gated channels activated by 1 mM cGMP in low divalent buffered saline. Currents were blocked by the application of micromolar concentrations of l-cis-diltiazem to the cytoplasmic side of the patch. The concentration dependence of block indicated that a single molecule was sufficient to block a channel and that all channels were susceptible to block. The dissociation constant for the rod channel was an order of magnitude smaller than for the cone channel, but the voltage dependence of block was nearly identical. The macroscopic current-voltage relation in the presence of blocker was inwardly rectifying and superficially resembled voltage-dependent block by an impermeant blocker occluding the ion-conducting pore of the channel. Block by diltiazem acting from the extracellular side of the channel was investigated by including 5 microM diltiazem in the recording pipette solution. The macroscopic current-voltage relation again showed inward rectification, inconsistent with the idea that diltiazem acts by occluding the pore at the external side. The kinetics of block by diltiazem applied to the intra- and extracellular side were measured in cone patches containing only a single channel. The unbinding rates were similar in both cases, suggesting a single binding site. Differences in the binding rate were consistent with greater accessibility to the binding site from the cytoplasmic side. Block from the cytoplasmic side was independent of pH, suggesting that the state of ionization of diltiazem was not related to its ability to block the channel in a voltage-dependent fashion. These observations are inconsistent with a pore-occluding blocker, but could be explained if the hydrophobic portion of diltiazem partitioned into the hydrophobic core of the channel protein, perhaps altering the gating of the channel.", "contents": "Block of the cyclic GMP-gated channel of vertebrate rod and cone photoreceptors by l-cis-diltiazem. Inside-out patches were excised from catfish rod or cone outer segments. Single channel and macroscopic currents were recorded from GMP-gated channels activated by 1 mM cGMP in low divalent buffered saline. Currents were blocked by the application of micromolar concentrations of l-cis-diltiazem to the cytoplasmic side of the patch. The concentration dependence of block indicated that a single molecule was sufficient to block a channel and that all channels were susceptible to block. The dissociation constant for the rod channel was an order of magnitude smaller than for the cone channel, but the voltage dependence of block was nearly identical. The macroscopic current-voltage relation in the presence of blocker was inwardly rectifying and superficially resembled voltage-dependent block by an impermeant blocker occluding the ion-conducting pore of the channel. Block by diltiazem acting from the extracellular side of the channel was investigated by including 5 microM diltiazem in the recording pipette solution. The macroscopic current-voltage relation again showed inward rectification, inconsistent with the idea that diltiazem acts by occluding the pore at the external side. The kinetics of block by diltiazem applied to the intra- and extracellular side were measured in cone patches containing only a single channel. The unbinding rates were similar in both cases, suggesting a single binding site. Differences in the binding rate were consistent with greater accessibility to the binding site from the cytoplasmic side. Block from the cytoplasmic side was independent of pH, suggesting that the state of ionization of diltiazem was not related to its ability to block the channel in a voltage-dependent fashion. These observations are inconsistent with a pore-occluding blocker, but could be explained if the hydrophobic portion of diltiazem partitioned into the hydrophobic core of the channel protein, perhaps altering the gating of the channel."} {"id": "PMID:1282146", "title": "Inhibition of heart calcium and chloride currents by sodium iodide. Specific attenuation in cAMP-dependent protein kinase-mediated regulation.", "content": "The enzymes cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) regulate the activity of cardiac ion channel proteins. In this study the whole-cell arrangement of the patch clamp technique was used to examine the effect of NaI on PKA-stimulated Cl- and Ca2+ channels in isolated guinea pig ventricular myocytes. Cl- currents (ICl) activated either by the beta-adrenergic agonist isoproterenol or the membrane-soluble cAMP analogue, 8-chlorphenylthio (8-CPT) cAMP, were greatly reduced in amplitude after substitution of an external solution containing 140 mM NaCl with a solution containing 140 mM NaI. This reduction was accompanied by a shift of -7 mV in the reversal potential (Erev) for ICl and could be reversed upon return to the NaCl external solution. Inhibition of ICl by NaI occurred in a concentration-dependent manner and was more pronounced for inward ICl (IC50 = 19 mM at -60 mV) than for outward ICl (IC50 = 60 mM at +60 mV). In contrast to ICl activated by PKA, ICl activated by PKC was slightly augmented in the presence of NaI and the Erev was found to shift by -15 mV. Based on these data, the relative permeability of I- to Cl- (PI/PCl) for this channel was calculated to be 1.79. NaI produced no change in the amplitude of inward calcium currents (ICa) recorded under basal conditions, but strongly inhibited ICa augmented by isoproterenol and 8-CPT cAMP, and during dialysis of cells with the catalytic subunit of PKA (CS). The in vitro incorporation of [gamma-32P]ATP into histone IIA and Kemptide, measured in the presence of PKA and cAMP, was not significantly different in assay mixtures containing salts of Cl- and I-. However, the ability of isoproterenol to augment basal ICa in whole-cell experiments was attenuated when experiments were carried out entirely in NaI external solution. Thus, the reduction in ICl and ICa observed in this study may result from a direct effect of I- on the phosphorylation/dephosphorylation of cardiac ion channel proteins or associated regulatory proteins.", "contents": "Inhibition of heart calcium and chloride currents by sodium iodide. Specific attenuation in cAMP-dependent protein kinase-mediated regulation. The enzymes cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) regulate the activity of cardiac ion channel proteins. In this study the whole-cell arrangement of the patch clamp technique was used to examine the effect of NaI on PKA-stimulated Cl- and Ca2+ channels in isolated guinea pig ventricular myocytes. Cl- currents (ICl) activated either by the beta-adrenergic agonist isoproterenol or the membrane-soluble cAMP analogue, 8-chlorphenylthio (8-CPT) cAMP, were greatly reduced in amplitude after substitution of an external solution containing 140 mM NaCl with a solution containing 140 mM NaI. This reduction was accompanied by a shift of -7 mV in the reversal potential (Erev) for ICl and could be reversed upon return to the NaCl external solution. Inhibition of ICl by NaI occurred in a concentration-dependent manner and was more pronounced for inward ICl (IC50 = 19 mM at -60 mV) than for outward ICl (IC50 = 60 mM at +60 mV). In contrast to ICl activated by PKA, ICl activated by PKC was slightly augmented in the presence of NaI and the Erev was found to shift by -15 mV. Based on these data, the relative permeability of I- to Cl- (PI/PCl) for this channel was calculated to be 1.79. NaI produced no change in the amplitude of inward calcium currents (ICa) recorded under basal conditions, but strongly inhibited ICa augmented by isoproterenol and 8-CPT cAMP, and during dialysis of cells with the catalytic subunit of PKA (CS). The in vitro incorporation of [gamma-32P]ATP into histone IIA and Kemptide, measured in the presence of PKA and cAMP, was not significantly different in assay mixtures containing salts of Cl- and I-. However, the ability of isoproterenol to augment basal ICa in whole-cell experiments was attenuated when experiments were carried out entirely in NaI external solution. Thus, the reduction in ICl and ICa observed in this study may result from a direct effect of I- on the phosphorylation/dephosphorylation of cardiac ion channel proteins or associated regulatory proteins."} {"id": "PMID:1282147", "title": "Tattooing as a risk of hepatitis C virus infection.", "content": "The association of hepatitis C virus (HCV) infection and tattooing was studied in 87 tattooed and 126 tattoo free healthy young men who did not engage in intravenous drug use or multiple sexual activity. Antibody against HCV (anti-HCV) was tested in serum specimens by enzyme immunoassay with C100-3, NS3, and core antigens; 11 of the 87 (12.6%) tattooed and 3 of the 126 (2.4%) tattoo free subjects were positive for anti-HCV (odds ratio = 5.9, 95% CI = 1.6-22.0). A relationship was demonstrated by an increased risk for HCV infection with an increasing number of tattooed site (P(trend) = 0.002). All but one of the 87 tattooed subjects had been infected by hepatitis B virus (HBV) and 25 were carriers of hepatitis B surface antigen (HBsAg). None of the 25 HBsAg carriers was positive for anti-HCV whereas 11 of the 62 HBsAg non-carriers had anti-HCV, suggesting a negative association between the HBsAg carriage and the long lasting anti-HCV (P = 0.02, Fisher's exact). The status of the tattooer was also an important determinant for HCV infection; the risk was higher if tattooing was done by a non-professional friend than by a professional tattooist. Tattooing, probably with improperly sterilized needles, can clearly pose an increased risk for HCV infection in Taiwan. This study indicates the need for legal standards for hygienic tattooing as part of preventive measures for the control of parenterally transmitted infections.", "contents": "Tattooing as a risk of hepatitis C virus infection. The association of hepatitis C virus (HCV) infection and tattooing was studied in 87 tattooed and 126 tattoo free healthy young men who did not engage in intravenous drug use or multiple sexual activity. Antibody against HCV (anti-HCV) was tested in serum specimens by enzyme immunoassay with C100-3, NS3, and core antigens; 11 of the 87 (12.6%) tattooed and 3 of the 126 (2.4%) tattoo free subjects were positive for anti-HCV (odds ratio = 5.9, 95% CI = 1.6-22.0). A relationship was demonstrated by an increased risk for HCV infection with an increasing number of tattooed site (P(trend) = 0.002). All but one of the 87 tattooed subjects had been infected by hepatitis B virus (HBV) and 25 were carriers of hepatitis B surface antigen (HBsAg). None of the 25 HBsAg carriers was positive for anti-HCV whereas 11 of the 62 HBsAg non-carriers had anti-HCV, suggesting a negative association between the HBsAg carriage and the long lasting anti-HCV (P = 0.02, Fisher's exact). The status of the tattooer was also an important determinant for HCV infection; the risk was higher if tattooing was done by a non-professional friend than by a professional tattooist. Tattooing, probably with improperly sterilized needles, can clearly pose an increased risk for HCV infection in Taiwan. This study indicates the need for legal standards for hygienic tattooing as part of preventive measures for the control of parenterally transmitted infections."} {"id": "PMID:1282148", "title": "Hepatitis C virus antibody detection by a line immunoassay and (near) full length genomic RNA detection by a new RNA-capture polymerase chain reaction.", "content": "A rapid and simple RNA-capture polymerase chain reaction assay (RCPA) for detection of hepatitis C virus (HCV) is described. The assay detects specifically the presence of (near) full length genomic RNA of HCV by capturing HCV-RNA at the 3' terminal end on magnetic beads, followed by cDNA synthesis and PCR with 5' end specific primers. Sera were obtained from 30 chimpanzees inoculated with non-A, non-B hepatitis material from various sources, 28-122 months after infection. The sera were tested for the presence of HCV-RNA by RCPA and for HCV antibodies by a Line ImmunoAssay (Inno-LIA HCV Ab). Both tests were compared and show a high degree of agreement. Screening of 30 chimpanzee sera revealed either clearing of the virus below detection level (22/30) or development of a HCV carrier state (8/30). Only 1 of 11 LIA-indeterminate samples was positive by RCPA. As the RCPA is more sensitive, it can be used to test for the presence of HCV in sera which are classified indeterminate by the LIA. The outcome of the infection seems to be independent of the nature of the inocula, suggesting that the individual immune response could determine either clearing of the virus or the development of chronic infection.", "contents": "Hepatitis C virus antibody detection by a line immunoassay and (near) full length genomic RNA detection by a new RNA-capture polymerase chain reaction. A rapid and simple RNA-capture polymerase chain reaction assay (RCPA) for detection of hepatitis C virus (HCV) is described. The assay detects specifically the presence of (near) full length genomic RNA of HCV by capturing HCV-RNA at the 3' terminal end on magnetic beads, followed by cDNA synthesis and PCR with 5' end specific primers. Sera were obtained from 30 chimpanzees inoculated with non-A, non-B hepatitis material from various sources, 28-122 months after infection. The sera were tested for the presence of HCV-RNA by RCPA and for HCV antibodies by a Line ImmunoAssay (Inno-LIA HCV Ab). Both tests were compared and show a high degree of agreement. Screening of 30 chimpanzee sera revealed either clearing of the virus below detection level (22/30) or development of a HCV carrier state (8/30). Only 1 of 11 LIA-indeterminate samples was positive by RCPA. As the RCPA is more sensitive, it can be used to test for the presence of HCV in sera which are classified indeterminate by the LIA. The outcome of the infection seems to be independent of the nature of the inocula, suggesting that the individual immune response could determine either clearing of the virus or the development of chronic infection."} {"id": "PMID:1282149", "title": "Efficacy of two temephos formulations against Chironomus salinarius (Diptera: Chironomidae) in the saltwater lagoon of Venice, Italy.", "content": "Two formulations of the organophosphorus insecticide, temephos (Abathion Granulare, 1% AI granular and Tambro Compresse, 2% AI tablet) were evaluated against Chironomus salinarius midge larvae in 50 x 50 m experimental plots in the saltwater lagoon of Venice, Italy. Each formulation was applied at 0.2 and 0.4 kg AI/ha. Abathion Granulare produced 56 to 73% larval reduction at 0.2 kg AI/ha and 69 to 83% reduction at 0.4 kg AI/ha during 3 wk after treatment. Abathion Granulare lost effectiveness at 4 wk after application at both rates. Posttreatment larval reductions resulting from Tambro Compresse applications ranged from 77 to 86% for 3 wk, and 82 to 92% for 4 wk at rates of 0.2 and 0.4 kg AI/ha, respectively. The tablet formulation (Tambro Compresse) gave better control of C. salinarius (magnitude and duration) than the granular formulation (Abathion Granulare) in these evaluations.", "contents": "Efficacy of two temephos formulations against Chironomus salinarius (Diptera: Chironomidae) in the saltwater lagoon of Venice, Italy. Two formulations of the organophosphorus insecticide, temephos (Abathion Granulare, 1% AI granular and Tambro Compresse, 2% AI tablet) were evaluated against Chironomus salinarius midge larvae in 50 x 50 m experimental plots in the saltwater lagoon of Venice, Italy. Each formulation was applied at 0.2 and 0.4 kg AI/ha. Abathion Granulare produced 56 to 73% larval reduction at 0.2 kg AI/ha and 69 to 83% reduction at 0.4 kg AI/ha during 3 wk after treatment. Abathion Granulare lost effectiveness at 4 wk after application at both rates. Posttreatment larval reductions resulting from Tambro Compresse applications ranged from 77 to 86% for 3 wk, and 82 to 92% for 4 wk at rates of 0.2 and 0.4 kg AI/ha, respectively. The tablet formulation (Tambro Compresse) gave better control of C. salinarius (magnitude and duration) than the granular formulation (Abathion Granulare) in these evaluations."} {"id": "PMID:1282152", "title": "Immunohistochemical analysis of cells attached to teflon membranes following guided tissue regeneration.", "content": "A wide panel of monoclonal antibodies to various keratins together with an anti-vimentin antibody to label mesenchymal cells were used to label cells attached to expanded polytetrafluorethylene (ePTFE) membranes removed 6 weeks postoperatively from 7 patients. All membranes demonstrated variable amounts of adherent tissue, within which vimentin-positive cells were detected. In 8 of the 18 samples, no epithelial cells were detected. Seven of the 18 samples demonstrated small groups of epithelial cells on both sides of the membranes, staining predominantly as basal cells. The remaining 3 samples were more densely populated by epithelium which expressed a diverse keratin profile. Thus, the membranes were successful in establishing mesenchymal cell proliferation, as evidenced by vimentin positivity, but did not totally exclude epithelium.", "contents": "Immunohistochemical analysis of cells attached to teflon membranes following guided tissue regeneration. A wide panel of monoclonal antibodies to various keratins together with an anti-vimentin antibody to label mesenchymal cells were used to label cells attached to expanded polytetrafluorethylene (ePTFE) membranes removed 6 weeks postoperatively from 7 patients. All membranes demonstrated variable amounts of adherent tissue, within which vimentin-positive cells were detected. In 8 of the 18 samples, no epithelial cells were detected. Seven of the 18 samples demonstrated small groups of epithelial cells on both sides of the membranes, staining predominantly as basal cells. The remaining 3 samples were more densely populated by epithelium which expressed a diverse keratin profile. Thus, the membranes were successful in establishing mesenchymal cell proliferation, as evidenced by vimentin positivity, but did not totally exclude epithelium."} {"id": "PMID:1282153", "title": "HIV inactivation in a bone allograft.", "content": "The use of exclusionary techniques in the procurement of donors for bone allografts greatly reduces chances for disease transmission. Furthermore, treatment of HIV with either chemical agents or strong acids will effectively inactivate the AIDS virus. These data are taken as indirect proof that the risk of obtaining AIDS from a freeze-dried bone allograft is highly remote. The purpose of this study is to obtain direct evidence that the processing of a demineralized freeze-dried bone allograft would render the allograft safe for human use. In Part I, human cortical bone was obtained from a cadaveric source and tested to be free of HIV contamination. The bone was spiked with 5.26 x 10(9) viral particles. This corresponded to 148 micrograms of total viral protein. In Part II, cortical bone was procured from a donor who died of AIDS. In both Parts I and II, the cortical bone was ground to yield particle sizes of 90 to 500 microns. Test samples were treated with a virucidal agent and demineralized in HCl. Control samples were left untreated. All samples were cocultivated with stimulated peripheral blood lymphocytes and assayed for p24 core protein, reverse transcriptase, and viral gag gene by polymerase chain reaction (PCR). In Part I, the HIV spiking experiment, untreated virus infected particulate bone was positive for HIV replication. Treated samples were negative when assayed for HIV. Bone samples in Part II, HIV infected bone, were positive by PCR. Replication of viable HIV could not be demonstrated after treatment. It was concluded that demineralization and treatment with a virucidal agent inactivates HIV in spiked and infected bone.", "contents": "HIV inactivation in a bone allograft. The use of exclusionary techniques in the procurement of donors for bone allografts greatly reduces chances for disease transmission. Furthermore, treatment of HIV with either chemical agents or strong acids will effectively inactivate the AIDS virus. These data are taken as indirect proof that the risk of obtaining AIDS from a freeze-dried bone allograft is highly remote. The purpose of this study is to obtain direct evidence that the processing of a demineralized freeze-dried bone allograft would render the allograft safe for human use. In Part I, human cortical bone was obtained from a cadaveric source and tested to be free of HIV contamination. The bone was spiked with 5.26 x 10(9) viral particles. This corresponded to 148 micrograms of total viral protein. In Part II, cortical bone was procured from a donor who died of AIDS. In both Parts I and II, the cortical bone was ground to yield particle sizes of 90 to 500 microns. Test samples were treated with a virucidal agent and demineralized in HCl. Control samples were left untreated. All samples were cocultivated with stimulated peripheral blood lymphocytes and assayed for p24 core protein, reverse transcriptase, and viral gag gene by polymerase chain reaction (PCR). In Part I, the HIV spiking experiment, untreated virus infected particulate bone was positive for HIV replication. Treated samples were negative when assayed for HIV. Bone samples in Part II, HIV infected bone, were positive by PCR. Replication of viable HIV could not be demonstrated after treatment. It was concluded that demineralization and treatment with a virucidal agent inactivates HIV in spiked and infected bone."} {"id": "PMID:1282154", "title": "A study of the bovine adrenal chromaffin nicotinic receptor using patch clamp and concentration-jump techniques.", "content": "1. Voltage clamp records have been obtained from bovine adrenal chromaffin cells in the outside-out and whole-cell configurations, in response to step changes of acetylcholine (ACh) concentration. The concentrations used ranged from 50 nM to 20 mM. 2. At high acetylcholine concentrations, the activation and desensitization kinetics of the nicotinic receptor, as observed in outside-out patches, may be described by a model incorporating a single, fast agonist binding step, and relatively slow isomerization to the open state. The affinity of the closed receptor for ACh is 310 microM, the channel opening rate constant is 460 s-1, and the closing rate constant is 29 s-1. 3. Single channel events, observed when nanomolar ACh concentrations are applied to whole cells, have two distinct channel lifetimes: 0.6 ms and 11-15 ms. The variation of the frequencies of the events with ACh concentration, suggests that the short lifetimes are openings of a singly liganded receptor and the longer lifetimes are openings of a doubly liganded receptor. 4. Only a single exponential associated with receptor desensitization is seen with outside-out patches, but two are seen with whole cells. It is postulated that there are two nicotinic receptor types present on adrenal chromaffin cells. 5. The rate of desensitization (9 s-1 and 26 s-1, whole cells; 24 s-1, patches), is fast enough to be significant in determining the open channel lifetime. 6. A sudden increase in current (rebound) is observed when a high concentration of ACh is abruptly removed from outside-out patches. This is evidence for a blocked state. The affinity of the blocking site for ACh is 1400 microM (outside-out patches). 7. The total number of activatable nicotinic channels per whole cell is estimated to be 2600.", "contents": "A study of the bovine adrenal chromaffin nicotinic receptor using patch clamp and concentration-jump techniques. 1. Voltage clamp records have been obtained from bovine adrenal chromaffin cells in the outside-out and whole-cell configurations, in response to step changes of acetylcholine (ACh) concentration. The concentrations used ranged from 50 nM to 20 mM. 2. At high acetylcholine concentrations, the activation and desensitization kinetics of the nicotinic receptor, as observed in outside-out patches, may be described by a model incorporating a single, fast agonist binding step, and relatively slow isomerization to the open state. The affinity of the closed receptor for ACh is 310 microM, the channel opening rate constant is 460 s-1, and the closing rate constant is 29 s-1. 3. Single channel events, observed when nanomolar ACh concentrations are applied to whole cells, have two distinct channel lifetimes: 0.6 ms and 11-15 ms. The variation of the frequencies of the events with ACh concentration, suggests that the short lifetimes are openings of a singly liganded receptor and the longer lifetimes are openings of a doubly liganded receptor. 4. Only a single exponential associated with receptor desensitization is seen with outside-out patches, but two are seen with whole cells. It is postulated that there are two nicotinic receptor types present on adrenal chromaffin cells. 5. The rate of desensitization (9 s-1 and 26 s-1, whole cells; 24 s-1, patches), is fast enough to be significant in determining the open channel lifetime. 6. A sudden increase in current (rebound) is observed when a high concentration of ACh is abruptly removed from outside-out patches. This is evidence for a blocked state. The affinity of the blocking site for ACh is 1400 microM (outside-out patches). 7. The total number of activatable nicotinic channels per whole cell is estimated to be 2600."} {"id": "PMID:1282155", "title": "Markov modelling of ensemble current relaxations: bovine adrenal nicotinic receptor currents analysed.", "content": "1. A general approach to the analysis of ensemble currents of ligand-gated channels is presented, with a variety of examples that include single and multiple agonist binding steps, desensitization and several blocking pathways. 2. The use of matrix methods to describe model reaction schemes leads to a simplification if the reaction scheme is irreversible: the product of the exponential relaxation rate constants is exactly equal to the product of the forward reaction steps. 3. This method of analysis applied to the bovine adrenal nicotinic receptor suggests that in the range of acetylcholine concentrations from 1 microM to 2 mM, a model with a single kinetically relevant agonist binding step is appropriate. 4. Complex models, to explain the presence of two desensitizing components in currents recorded from whole cells, may be discounted in favour of two distinct receptor types. 5. A simple model of open channel block is discounted, and desensitization of the blocked state proposed.", "contents": "Markov modelling of ensemble current relaxations: bovine adrenal nicotinic receptor currents analysed. 1. A general approach to the analysis of ensemble currents of ligand-gated channels is presented, with a variety of examples that include single and multiple agonist binding steps, desensitization and several blocking pathways. 2. The use of matrix methods to describe model reaction schemes leads to a simplification if the reaction scheme is irreversible: the product of the exponential relaxation rate constants is exactly equal to the product of the forward reaction steps. 3. This method of analysis applied to the bovine adrenal nicotinic receptor suggests that in the range of acetylcholine concentrations from 1 microM to 2 mM, a model with a single kinetically relevant agonist binding step is appropriate. 4. Complex models, to explain the presence of two desensitizing components in currents recorded from whole cells, may be discounted in favour of two distinct receptor types. 5. A simple model of open channel block is discounted, and desensitization of the blocked state proposed."} {"id": "PMID:1282156", "title": "Ca(2+)-activated K+ channels modulate muscarinic secretion in cat chromaffin cells.", "content": "1. This study was aimed at testing the hypothesis that Ca(2+)-dependent K+ channels regulate the release of catecholamines mediated by muscarinic stimulation of cat adrenal chromaffin cells. Two parameters were measured: the secretory response to brief pulses of methacholine (100 microM for 10 s) in intact cat adrenal glands perfused at a high rate with oxygenated Krebs solution; and the changes in cytosolic Ca2+ concentrations, [Ca2+]i, produced by puff applications of methacholine pulses (also 100 microM for 10 s) in isolated single cat adrenal chromaffin cells loaded with Fura-2. 2. A pulse of methacholine released 805 +/- 164 ng of catecholamines (mean of thirty-two pulses). d-Tubocurarine (DTC) increased the secretory response in a concentration-dependent manner. The maximum increase (around 1000 ng catecholamines over control values) was reached at 100 microM-DTC and the EC50 was around 10 microM. 3. The secretory responses to methacholine alone, or to the combination of methacholine plus DTC, were strongly dependent on the extracellular Ca2+ concentration, [Ca2+]o. Thus Ca2+o removal from the perfusing solution for 5-10 min abolished catecholamine release. 4. At 0.1 microM, isradipine (an L-type Ca2+ channel blocker) inhibited by 71% the secretory response to DTC plus methacholine. At 1 microM, Bay K 8644 (an L-type Ca2+ channel activator) increased 2-fold the secretory response to DTC plus methacholine (2746 ng of catecholamines). 5. Apamin (1 microM) increased 3.5-fold the secretory response to methacholine pulses (from 500 to 1800 ng of catecholamines). 6. Methacholine pulses enhanced [Ca2+]i from the resting level of 100 nM to a peak of 1000 nM which quickly declined to basal level. DTC (100 microM) enhanced by 20% the [Ca2+]i peak and substantially prolonged its duration. 7. Apamin (1 microM) increased by 60% the [Ca2+]i peak evoked by methacholine, and delayed the initiation of decline of the [Ca2+]i peak. 8. These results are compatible with the idea that muscarinic stimulation depolarizes the cat adrenal chromaffin cell through an unidentified mechanism. Depolarization is probably counteracted by activation of Ca2+i-dependent K+ channels. Therefore, inhibition of these channels enhances depolarization and firing of action potentials which activate voltage-dependent L-type Ca2+ channels to increase further the Ca2+i signal and the secretory response. Thus Ca2+i-dependent K+ channels, probably of the small-conductance type (SK), seem to be involved in the modulation of muscarinic-evoked catecholamine release responses in cat adrenal chromaffin cells.", "contents": "Ca(2+)-activated K+ channels modulate muscarinic secretion in cat chromaffin cells. 1. This study was aimed at testing the hypothesis that Ca(2+)-dependent K+ channels regulate the release of catecholamines mediated by muscarinic stimulation of cat adrenal chromaffin cells. Two parameters were measured: the secretory response to brief pulses of methacholine (100 microM for 10 s) in intact cat adrenal glands perfused at a high rate with oxygenated Krebs solution; and the changes in cytosolic Ca2+ concentrations, [Ca2+]i, produced by puff applications of methacholine pulses (also 100 microM for 10 s) in isolated single cat adrenal chromaffin cells loaded with Fura-2. 2. A pulse of methacholine released 805 +/- 164 ng of catecholamines (mean of thirty-two pulses). d-Tubocurarine (DTC) increased the secretory response in a concentration-dependent manner. The maximum increase (around 1000 ng catecholamines over control values) was reached at 100 microM-DTC and the EC50 was around 10 microM. 3. The secretory responses to methacholine alone, or to the combination of methacholine plus DTC, were strongly dependent on the extracellular Ca2+ concentration, [Ca2+]o. Thus Ca2+o removal from the perfusing solution for 5-10 min abolished catecholamine release. 4. At 0.1 microM, isradipine (an L-type Ca2+ channel blocker) inhibited by 71% the secretory response to DTC plus methacholine. At 1 microM, Bay K 8644 (an L-type Ca2+ channel activator) increased 2-fold the secretory response to DTC plus methacholine (2746 ng of catecholamines). 5. Apamin (1 microM) increased 3.5-fold the secretory response to methacholine pulses (from 500 to 1800 ng of catecholamines). 6. Methacholine pulses enhanced [Ca2+]i from the resting level of 100 nM to a peak of 1000 nM which quickly declined to basal level. DTC (100 microM) enhanced by 20% the [Ca2+]i peak and substantially prolonged its duration. 7. Apamin (1 microM) increased by 60% the [Ca2+]i peak evoked by methacholine, and delayed the initiation of decline of the [Ca2+]i peak. 8. These results are compatible with the idea that muscarinic stimulation depolarizes the cat adrenal chromaffin cell through an unidentified mechanism. Depolarization is probably counteracted by activation of Ca2+i-dependent K+ channels. Therefore, inhibition of these channels enhances depolarization and firing of action potentials which activate voltage-dependent L-type Ca2+ channels to increase further the Ca2+i signal and the secretory response. Thus Ca2+i-dependent K+ channels, probably of the small-conductance type (SK), seem to be involved in the modulation of muscarinic-evoked catecholamine release responses in cat adrenal chromaffin cells."} {"id": "PMID:1282157", "title": "Simultaneous visualization of cortical barrels and horseradish peroxidase-injected layer 5b vibrissa neurones in the rat.", "content": "1. Using diaminobenzidine (DAB) as a chromagen, horseradish peroxidase-injected neurones and cytochrome oxidase-stained barrels were visualized simultaneously in the rat vibrissa cortex. Neurones were initially tested during extracellular recording for responses to whisker deflections. This was followed by intracellular injection of the soma with horseradish peroxidase (HRP) and histological processing to visualize the HRP-stained neurone in an incubation solution which contained, in addition to DAB, cytochrome C for cytochrome oxidase (CO) reaction of the barrels. 2. Recording and intracellular staining were made in layer 5b under urethane anaesthesia. CO-stained barrels were observed in layer 4. Physiologically and morphologically characterized neurones were mostly large pyramidal neurones that responded to more than one whisker and displayed transient-type responses. 3. In tangential sections, the apical dendrite of the HRP-filled neurone was followed from the soma level upward as it ascended through the barrelfield in layer 4. The cross-section of the apical dendrite was found in the periphery of the CO-stained barrel. Using the apical dendrite as a guide, the basal dendritic field of the layer 5b pyramidal neurone was aligned on the pattern of layer 4 barrels. The soma was seen to project basal dendrites in all directions, involving one or two neighbouring barrels/columns. 4. In sixteen neurones examined in tangential sections, a complete spatial tuning map constructed by measuring sensitivity of the neurone to different whiskers could be compared to the basal dendritic field in relation to the pattern of overlying layer 4 barrels. The mean receptive field size in terms of the number of effective whiskers was 5.8 whereas the mean dendritic field size in terms of the number of barrels/columns involved was 2.2. In addition to the well-documented role of intracortical connectivity in elaboration of multi-whisker receptor fields in the cortical neurones, the role played by direct inputs from multi-whisker thalamic ventrobasal neurones was discussed.", "contents": "Simultaneous visualization of cortical barrels and horseradish peroxidase-injected layer 5b vibrissa neurones in the rat. 1. Using diaminobenzidine (DAB) as a chromagen, horseradish peroxidase-injected neurones and cytochrome oxidase-stained barrels were visualized simultaneously in the rat vibrissa cortex. Neurones were initially tested during extracellular recording for responses to whisker deflections. This was followed by intracellular injection of the soma with horseradish peroxidase (HRP) and histological processing to visualize the HRP-stained neurone in an incubation solution which contained, in addition to DAB, cytochrome C for cytochrome oxidase (CO) reaction of the barrels. 2. Recording and intracellular staining were made in layer 5b under urethane anaesthesia. CO-stained barrels were observed in layer 4. Physiologically and morphologically characterized neurones were mostly large pyramidal neurones that responded to more than one whisker and displayed transient-type responses. 3. In tangential sections, the apical dendrite of the HRP-filled neurone was followed from the soma level upward as it ascended through the barrelfield in layer 4. The cross-section of the apical dendrite was found in the periphery of the CO-stained barrel. Using the apical dendrite as a guide, the basal dendritic field of the layer 5b pyramidal neurone was aligned on the pattern of layer 4 barrels. The soma was seen to project basal dendrites in all directions, involving one or two neighbouring barrels/columns. 4. In sixteen neurones examined in tangential sections, a complete spatial tuning map constructed by measuring sensitivity of the neurone to different whiskers could be compared to the basal dendritic field in relation to the pattern of overlying layer 4 barrels. The mean receptive field size in terms of the number of effective whiskers was 5.8 whereas the mean dendritic field size in terms of the number of barrels/columns involved was 2.2. In addition to the well-documented role of intracortical connectivity in elaboration of multi-whisker receptor fields in the cortical neurones, the role played by direct inputs from multi-whisker thalamic ventrobasal neurones was discussed."} {"id": "PMID:1282158", "title": "Stretch-activated non-selective cation channels in the antiluminal membrane of porcine cerebral capillaries.", "content": "1. Single stretch-activated (SA) channels have been studied in isolated brain capillary endothelial cells as well as in the antiluminal membrane of intact porcine cerebral capillaries using the patch-clamp recording technique. 2. The SA channels were found to be cation selective and permeable to Na+, K+, Ba2+ and Ca2+. 3. With monovalent cations in the patch pipette, the channels showed inward rectification in cell-attached patches with a single-channel conductance of 37 pS at negative and 24 pS at positive clamp potentials. 4. With either 70 mM-Ca2+ or Ba2+ in the patch pipette, the current-voltage relation was linear with slope conductances of 16 and 19 pS, respectively. 5. Mean channel open probability increased with increasing pressure and with depolarizing clamp potentials. 6. Cell swelling induced by hypotonic shock activated the SA channels in cell-attached experiments. 7. The SA channel may be involved in cell volume or blood flow regulation. The contribution of these channels to the regulation of cerebrospinal salt and water content, especially in brain oedema, is discussed.", "contents": "Stretch-activated non-selective cation channels in the antiluminal membrane of porcine cerebral capillaries. 1. Single stretch-activated (SA) channels have been studied in isolated brain capillary endothelial cells as well as in the antiluminal membrane of intact porcine cerebral capillaries using the patch-clamp recording technique. 2. The SA channels were found to be cation selective and permeable to Na+, K+, Ba2+ and Ca2+. 3. With monovalent cations in the patch pipette, the channels showed inward rectification in cell-attached patches with a single-channel conductance of 37 pS at negative and 24 pS at positive clamp potentials. 4. With either 70 mM-Ca2+ or Ba2+ in the patch pipette, the current-voltage relation was linear with slope conductances of 16 and 19 pS, respectively. 5. Mean channel open probability increased with increasing pressure and with depolarizing clamp potentials. 6. Cell swelling induced by hypotonic shock activated the SA channels in cell-attached experiments. 7. The SA channel may be involved in cell volume or blood flow regulation. The contribution of these channels to the regulation of cerebrospinal salt and water content, especially in brain oedema, is discussed."} {"id": "PMID:1282159", "title": "Inhibition of cytokine-induced nitric oxide production by transforming growth factor-beta 1 in human smooth muscle cells.", "content": "1. Experiments were performed to investigate the effects of human recombinant interleukin-1 beta on the production of vasoactive substances by human aortic smooth muscle cells in culture. Smooth muscle cells were cultured either on microcarrier beads for bioassay experiments, or in multiwell plates for the determination of nitrite levels. 2. Cells were grown on microcarrier beads, treated with interleukin-1 beta or vehicle (control) for 24 h, and packed in a column which was perfused with oxygenated Krebs-Ringer solution in the presence of indomethacin. The activity of the perfusates was bioassayed by measuring the changes in tension of a contracted ring of Wistar rat aorta without endothelium, and by evaluating the modulation of thrombin-induced platelet aggregation. 3. Perfusates from interleukin-1 beta treated cells evoked relaxations of the contracted detector tissues, and microcarrier beads covered with treated cells inhibited thrombin-induced platelet aggregation. Superoxide dismutase enhanced these effects whereas Methylene Blue abolished them. Control cells evoke neither relaxation nor inhibition of platelet aggregation. Interleukin-1 beta induced a time- and concentration-dependent production of nitrite. Cycloheximide and nitro-L-arginine inhibited the relaxations and the production of nitrite evoked by interleukin-1 beta-treated cells. L-Arginine but not D-arginine overcame the blockade elicited by nitro-L-arginine. Transforming growth factor-beta 1 reduced the interleukin-1 beta-dependent generation of nitrite by cultured smooth muscle cells and relaxation of contracted bioassay tissues. 4. Interleukin-1 beta, transforming growth factor-beta 1, Methylene Blue and L-arginine-related compounds did not induce significant variations of tension of the detector rings. 5. These data demonstrate that the inflammatory and immunological mediator interleukin-1 can stimulate the production of a nitric oxide-like substance(s) in cultured human smooth muscle cells leading to the activation of soluble guanylate cyclase. Liberation of transforming growth factor-beta by activated platelets may inhibit these reactions.", "contents": "Inhibition of cytokine-induced nitric oxide production by transforming growth factor-beta 1 in human smooth muscle cells. 1. Experiments were performed to investigate the effects of human recombinant interleukin-1 beta on the production of vasoactive substances by human aortic smooth muscle cells in culture. Smooth muscle cells were cultured either on microcarrier beads for bioassay experiments, or in multiwell plates for the determination of nitrite levels. 2. Cells were grown on microcarrier beads, treated with interleukin-1 beta or vehicle (control) for 24 h, and packed in a column which was perfused with oxygenated Krebs-Ringer solution in the presence of indomethacin. The activity of the perfusates was bioassayed by measuring the changes in tension of a contracted ring of Wistar rat aorta without endothelium, and by evaluating the modulation of thrombin-induced platelet aggregation. 3. Perfusates from interleukin-1 beta treated cells evoked relaxations of the contracted detector tissues, and microcarrier beads covered with treated cells inhibited thrombin-induced platelet aggregation. Superoxide dismutase enhanced these effects whereas Methylene Blue abolished them. Control cells evoke neither relaxation nor inhibition of platelet aggregation. Interleukin-1 beta induced a time- and concentration-dependent production of nitrite. Cycloheximide and nitro-L-arginine inhibited the relaxations and the production of nitrite evoked by interleukin-1 beta-treated cells. L-Arginine but not D-arginine overcame the blockade elicited by nitro-L-arginine. Transforming growth factor-beta 1 reduced the interleukin-1 beta-dependent generation of nitrite by cultured smooth muscle cells and relaxation of contracted bioassay tissues. 4. Interleukin-1 beta, transforming growth factor-beta 1, Methylene Blue and L-arginine-related compounds did not induce significant variations of tension of the detector rings. 5. These data demonstrate that the inflammatory and immunological mediator interleukin-1 can stimulate the production of a nitric oxide-like substance(s) in cultured human smooth muscle cells leading to the activation of soluble guanylate cyclase. Liberation of transforming growth factor-beta by activated platelets may inhibit these reactions."} {"id": "PMID:1282160", "title": "Treatment of metastatic testicular tumours with bleomycin, etoposide, cisplatin and vincristine (BEPV).", "content": "Between August 1983 and December 1988, 47 patients with metastatic testicular tumours (44 non-seminomatous, three seminomas) were treated with two to six courses of bleomycin, etoposide, cisplatin and vincristine (BEPV). Five stage I tumours were included, three because of raised tumour markers following orchidectomy, one with vascular invasion of spermatic cord vessels and the other with both these features. Forty-four patients (93.6%) are alive and disease free 12-75 months (median 39 months) after completion of BEPV. Further treatment was necessary in 12 of the survivors. Eight had residual disease excised, one of whom received radiotherapy, one additional chemotherapy and one both radiotherapy and chemotherapy. Of the remaining four, two had radiotherapy and two second line chemotherapy. Thirty-one non-seminomatous and the three seminoma patients had small volume disease and all are in complete remission. Ten of the 13 patients with bulky disease are alive. It is concluded that BEPV is a well-tolerated, effective, first line therapy for patients with metastatic testicular tumour.", "contents": "Treatment of metastatic testicular tumours with bleomycin, etoposide, cisplatin and vincristine (BEPV). Between August 1983 and December 1988, 47 patients with metastatic testicular tumours (44 non-seminomatous, three seminomas) were treated with two to six courses of bleomycin, etoposide, cisplatin and vincristine (BEPV). Five stage I tumours were included, three because of raised tumour markers following orchidectomy, one with vascular invasion of spermatic cord vessels and the other with both these features. Forty-four patients (93.6%) are alive and disease free 12-75 months (median 39 months) after completion of BEPV. Further treatment was necessary in 12 of the survivors. Eight had residual disease excised, one of whom received radiotherapy, one additional chemotherapy and one both radiotherapy and chemotherapy. Of the remaining four, two had radiotherapy and two second line chemotherapy. Thirty-one non-seminomatous and the three seminoma patients had small volume disease and all are in complete remission. Ten of the 13 patients with bulky disease are alive. It is concluded that BEPV is a well-tolerated, effective, first line therapy for patients with metastatic testicular tumour."} {"id": "PMID:1282161", "title": "On the early emergence of reverse transcription: theoretical basis and experimental evidence.", "content": "Reverse transcriptase (RT) was first discovered as an essential catalyst in the biological cycle of retroviruses. However, in the past years evidence has accumulated showing that RTs are involved in a surprisingly large number of RNA-mediated transpositional events that include both viral and nonviral genetic entities. Although it is probable that some RT-bearing genetic elements like the different types of AIDS viruses and the mammalian LINE family have arisen in recent geological times, the possibility that reverse transcription first took place in the early Archean is supported by (1) the hypothesis that RNA preceded DNA as cellular genetic material; (2) the existence of homologous regions of the subunit tau of the E. coli DNA polymerase III with the simian immunodeficiency virus RT, the hepatitis B virus RT, and the beta' subunit of the E. coli RNA polymerase (McHenry et al. 1988); (3) the presence of several conserved motifs, including a 14-amino-acid segment that consists of an Asp-Asp pair flanked by hydrophobic amino acids, which are found in all RTs and in most cellular and viral RNA polymerases. However, whether extant RTs descend from the primitive polymerase involved in the RNA-to-DNA transition remains unproven. Substrate specificity of the AMV and HIV-1 RTs can be modified in the presence of Mn2+, a cation which allows them to add ribonucleotides to an oligo (dG) primer in a template-dependent reaction. This change in specificity is comparable to that observed under similar conditions in other nucleic acid polymerases. This experimentally induced change in RT substrate specificity may explain previous observations on the misincorporation of ribonucleotides by the Maloney murine sarcoma virus RT in the minus and plus DNA of this retrovirus (Chen and Temin 1980). Our results also suggest that HIV-infected macrophages and T-cell cells may contain mixed polynucleotides containing both ribo- and deoxyribonucleotides. The evolutionary significance of these changes in substrate specificities of nucleic acid polymerases is also discussed.", "contents": "On the early emergence of reverse transcription: theoretical basis and experimental evidence. Reverse transcriptase (RT) was first discovered as an essential catalyst in the biological cycle of retroviruses. However, in the past years evidence has accumulated showing that RTs are involved in a surprisingly large number of RNA-mediated transpositional events that include both viral and nonviral genetic entities. Although it is probable that some RT-bearing genetic elements like the different types of AIDS viruses and the mammalian LINE family have arisen in recent geological times, the possibility that reverse transcription first took place in the early Archean is supported by (1) the hypothesis that RNA preceded DNA as cellular genetic material; (2) the existence of homologous regions of the subunit tau of the E. coli DNA polymerase III with the simian immunodeficiency virus RT, the hepatitis B virus RT, and the beta' subunit of the E. coli RNA polymerase (McHenry et al. 1988); (3) the presence of several conserved motifs, including a 14-amino-acid segment that consists of an Asp-Asp pair flanked by hydrophobic amino acids, which are found in all RTs and in most cellular and viral RNA polymerases. However, whether extant RTs descend from the primitive polymerase involved in the RNA-to-DNA transition remains unproven. Substrate specificity of the AMV and HIV-1 RTs can be modified in the presence of Mn2+, a cation which allows them to add ribonucleotides to an oligo (dG) primer in a template-dependent reaction. This change in specificity is comparable to that observed under similar conditions in other nucleic acid polymerases. This experimentally induced change in RT substrate specificity may explain previous observations on the misincorporation of ribonucleotides by the Maloney murine sarcoma virus RT in the minus and plus DNA of this retrovirus (Chen and Temin 1980). Our results also suggest that HIV-infected macrophages and T-cell cells may contain mixed polynucleotides containing both ribo- and deoxyribonucleotides. The evolutionary significance of these changes in substrate specificities of nucleic acid polymerases is also discussed."} {"id": "PMID:1282162", "title": "A redefinition of the Asp-Asp domain of reverse transcriptases.", "content": "The rules defining the Asp-Asp domain of RNA-dependent polymerases deduced by Argos (1988) were tested in a set of 53 putative reverse transcriptases (RTs) sequences. Since it was found that some of these rules are not followed by RTs coded by bacteria, group II introns, and non-LTR retrotransposons, we present here a more strict definition of the Asp-Asp domain.", "contents": "A redefinition of the Asp-Asp domain of reverse transcriptases. The rules defining the Asp-Asp domain of RNA-dependent polymerases deduced by Argos (1988) were tested in a set of 53 putative reverse transcriptases (RTs) sequences. Since it was found that some of these rules are not followed by RTs coded by bacteria, group II introns, and non-LTR retrotransposons, we present here a more strict definition of the Asp-Asp domain."} {"id": "PMID:1282163", "title": "[Multifactorial analysis of the pyuria after transurethral prostatectomy].", "content": "Multifactorial analysis on 395 patients revealed important factors which prolong the pyuria after transurethral prostatectomy. They were the age of the patient, anemia and leukocytosis before surgery. These are factors which relate with the defense mechanism of the patient. Local factors, such as the duration of indwelling urethral catheter, the size of the prostate or prostatic bed and preoperative infection, were not so important for prolonging the pyuria after transurethral prostatectomy. The time of the resection and weight of the prostate had an intimate relation each other, and the former was the more important factor. The use of antimicrobials probably controlled these local risk factors, thus making them unimportant in the prolongation of the pyuria after transurethral prostatectomy.", "contents": "[Multifactorial analysis of the pyuria after transurethral prostatectomy]. Multifactorial analysis on 395 patients revealed important factors which prolong the pyuria after transurethral prostatectomy. They were the age of the patient, anemia and leukocytosis before surgery. These are factors which relate with the defense mechanism of the patient. Local factors, such as the duration of indwelling urethral catheter, the size of the prostate or prostatic bed and preoperative infection, were not so important for prolonging the pyuria after transurethral prostatectomy. The time of the resection and weight of the prostate had an intimate relation each other, and the former was the more important factor. The use of antimicrobials probably controlled these local risk factors, thus making them unimportant in the prolongation of the pyuria after transurethral prostatectomy."} {"id": "PMID:1282164", "title": "[Intralymphatic drug therapy--a pathogenetically substantiated method of treatment in peritonitis].", "content": "The method of endolymphatic drug therapy (EDT) suggested by the authors has some advantages over the method of endoarterial therapy (which has proved to be effective in clinical practice) because it is aimed not only at control of the microbial flora, but also at correction of rheologic and microcirculatory disorders, improvement of the processes of tissue respiration and metabolism, stimulation of the intestine, prevention of the damaging effect of enzymes, toxins, and poisons on the organs and tissues of the body, and at correction of disorders of the immune status with promotion of the barrier function of the lymph nodes and the lymphatic system as a whole. EDT may be recommended for wide use in the clinic in the treatment of patients with peritonitis and other serious surgical infections unresponsive to the generally applied methods of management.", "contents": "[Intralymphatic drug therapy--a pathogenetically substantiated method of treatment in peritonitis]. The method of endolymphatic drug therapy (EDT) suggested by the authors has some advantages over the method of endoarterial therapy (which has proved to be effective in clinical practice) because it is aimed not only at control of the microbial flora, but also at correction of rheologic and microcirculatory disorders, improvement of the processes of tissue respiration and metabolism, stimulation of the intestine, prevention of the damaging effect of enzymes, toxins, and poisons on the organs and tissues of the body, and at correction of disorders of the immune status with promotion of the barrier function of the lymph nodes and the lymphatic system as a whole. EDT may be recommended for wide use in the clinic in the treatment of patients with peritonitis and other serious surgical infections unresponsive to the generally applied methods of management."} {"id": "PMID:1282165", "title": "[Surgical treatment of lung cancer: therapy or palliative?].", "content": "In spite of the revolutionary innovations concerning diagnostic and intensive care techniques as well as better understanding of tumor biology during the last decade, rates of resection and long-term survival in bronchogenic carcinoma could not be improved. All efforts are to be done in investigation on practicable, suitable, and supportable screening programs for early recognition of tumors in the first stages.", "contents": "[Surgical treatment of lung cancer: therapy or palliative?]. In spite of the revolutionary innovations concerning diagnostic and intensive care techniques as well as better understanding of tumor biology during the last decade, rates of resection and long-term survival in bronchogenic carcinoma could not be improved. All efforts are to be done in investigation on practicable, suitable, and supportable screening programs for early recognition of tumors in the first stages."} {"id": "PMID:1282168", "title": "Molecular mechanism of action of nicorandil.", "content": "Nicorandil relaxes coronary vascular smooth muscle by stimulating guanylyl cyclase and increasing cyclic GMP (cGMP) levels (as shown first in our laboratory) as well as by a second mechanism resulting in activation of K+ channels and hyperpolarization. Therefore, we studied the relative contributions of either mechanism to the overall response in bovine circular strips of coronary arteries by simultaneously measuring changes in length and in cGMP levels through radioimmunoassay. Blockade by 10 microM methylene blue of the cGMP increases in strips precontracted by 1 microM of the thromboxane A2 analogue U46619 reduced nicorandil-induced relaxation to 30-50%, and there were no significant changes in cGMP levels. Suppression of the hyperpolarizing component of nicorandil by 80.4 mM K+ or 1 microM glibenclamide in precontracted strips reduced nicorandil relaxation to 50% (K+) or shifted the dose response to the right by a factor of two (glibenclamide) without alteration of increases in cGMP. A quantitative separation of both mechanisms of action was obtained by comparing the correlation between increases in cGMP and relaxation under conditions of inhibited versus noninhibited hyperpolarization. The results indicate that cGMP contributes to the total relaxing effect of nicorandil by 30-40% at low concentrations and 80-90% at high concentrations of nicorandil. From the experiments with glibenclamide, it can be concluded that the probable mechanism by which nicorandil hyperpolarizes is opening glibenclamide-sensitive K+ channels in coronary vascular smooth muscle and that this latter effect mimics those of other K+ channel openers such as cromakalim or pinacidil.", "contents": "Molecular mechanism of action of nicorandil. Nicorandil relaxes coronary vascular smooth muscle by stimulating guanylyl cyclase and increasing cyclic GMP (cGMP) levels (as shown first in our laboratory) as well as by a second mechanism resulting in activation of K+ channels and hyperpolarization. Therefore, we studied the relative contributions of either mechanism to the overall response in bovine circular strips of coronary arteries by simultaneously measuring changes in length and in cGMP levels through radioimmunoassay. Blockade by 10 microM methylene blue of the cGMP increases in strips precontracted by 1 microM of the thromboxane A2 analogue U46619 reduced nicorandil-induced relaxation to 30-50%, and there were no significant changes in cGMP levels. Suppression of the hyperpolarizing component of nicorandil by 80.4 mM K+ or 1 microM glibenclamide in precontracted strips reduced nicorandil relaxation to 50% (K+) or shifted the dose response to the right by a factor of two (glibenclamide) without alteration of increases in cGMP. A quantitative separation of both mechanisms of action was obtained by comparing the correlation between increases in cGMP and relaxation under conditions of inhibited versus noninhibited hyperpolarization. The results indicate that cGMP contributes to the total relaxing effect of nicorandil by 30-40% at low concentrations and 80-90% at high concentrations of nicorandil. From the experiments with glibenclamide, it can be concluded that the probable mechanism by which nicorandil hyperpolarizes is opening glibenclamide-sensitive K+ channels in coronary vascular smooth muscle and that this latter effect mimics those of other K+ channel openers such as cromakalim or pinacidil."} {"id": "PMID:1282169", "title": "Treatment of ischemic heart disease in the 1990s: key issues for the physician.", "content": "During recent years, understanding of the basic pathology, pathophysiology, and morbid risk of ischemic heart disease has increased immensely, but a wide gulf still exists between such knowledge and its practical application to the individual patient. Although the treatment of ischemic heart disease continues to pose many dilemmas for the physician in the 1990s, the key issues are easy to define, particularly with regard to pharmacotherapy. The basic pathologic processes and their rate of development and progression, their pathophysiologic consequences, and their morbidity and mortality risks are becoming increasingly clear. Until methods are developed to reconstitute the obstructed coronary arteries, clinical attention must be directed primarily to alleviating symptoms and ECG signs of myocardial ischemia and improving the deranged hemodynamic disorder. These primary objectives are now achievable with modern anti-ischemic drugs such as nicorandil. With the availability of efficacious drugs against clinical symptoms, ECG signs, and hemodynamic associates of ischemic heart disease, clinical attention must be redirected to retardation or even regression of the primary myocardial ischemic syndrome. This therapeutic goal can be achieved only by correction of the secondary risk factors that are present in many patients with ischemic heart disease. Only by such a comprehensive approach, namely, that of treatment allied to prevention, can the gap between knowledge and its practical application to the individual patient be narrowed.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Treatment of ischemic heart disease in the 1990s: key issues for the physician. During recent years, understanding of the basic pathology, pathophysiology, and morbid risk of ischemic heart disease has increased immensely, but a wide gulf still exists between such knowledge and its practical application to the individual patient. Although the treatment of ischemic heart disease continues to pose many dilemmas for the physician in the 1990s, the key issues are easy to define, particularly with regard to pharmacotherapy. The basic pathologic processes and their rate of development and progression, their pathophysiologic consequences, and their morbidity and mortality risks are becoming increasingly clear. Until methods are developed to reconstitute the obstructed coronary arteries, clinical attention must be directed primarily to alleviating symptoms and ECG signs of myocardial ischemia and improving the deranged hemodynamic disorder. These primary objectives are now achievable with modern anti-ischemic drugs such as nicorandil. With the availability of efficacious drugs against clinical symptoms, ECG signs, and hemodynamic associates of ischemic heart disease, clinical attention must be redirected to retardation or even regression of the primary myocardial ischemic syndrome. This therapeutic goal can be achieved only by correction of the secondary risk factors that are present in many patients with ischemic heart disease. Only by such a comprehensive approach, namely, that of treatment allied to prevention, can the gap between knowledge and its practical application to the individual patient be narrowed.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282170", "title": "Relaxation of human coronary artery and arteria mammaria by K(+)-channel openers.", "content": "Three agents with K(+)-channel-opening activity--nicorandil, bimakalim (EMD 52692), and EMD 56431--were tested for vasorelaxation abilities in human coronary artery and human arteria mammaria. The potency orders were bimakalim = EMD 56431 >> nicorandil for relaxation in human coronary artery and bimakalim = EMD 56431 >> nicorandil in human arteria mammaria. These data demonstrate that K(+)-channel openers are effective vasorelaxant agents in human coronary artery and human arteria mammaria. Bimakalim and EMD 56431 were more potent than nicorandil, a drug that also activates guanylate cyclase.", "contents": "Relaxation of human coronary artery and arteria mammaria by K(+)-channel openers. Three agents with K(+)-channel-opening activity--nicorandil, bimakalim (EMD 52692), and EMD 56431--were tested for vasorelaxation abilities in human coronary artery and human arteria mammaria. The potency orders were bimakalim = EMD 56431 >> nicorandil for relaxation in human coronary artery and bimakalim = EMD 56431 >> nicorandil in human arteria mammaria. These data demonstrate that K(+)-channel openers are effective vasorelaxant agents in human coronary artery and human arteria mammaria. Bimakalim and EMD 56431 were more potent than nicorandil, a drug that also activates guanylate cyclase."} {"id": "PMID:1282171", "title": "Differential effects of nitrovasodilators, K(+)-channel openers, and nicorandil on large and small coronary arteries in conscious dogs.", "content": "When administered intravenously to conscious dogs, nicorandil, nitrovasodilators (nitroglycerin and SIN-1), and the K(+)-channel opener cromakalim exhibited marked differential effects on large epicardial and small resistance coronary arteries. Nitrovasodilators markedly increased the left circumflex coronary artery diameter at doses at which coronary resistance was not significantly decreased. In contrast, both cromakalim and nicorandil dilated large and small coronary arteries in the same conditions. When coronary blood flow was held to its control value by partial inflation of a hydraulic occluder implanted around the artery, the nitroglycerin- and nicorandil-induced increases in large coronary diameter remained unchanged whereas the response to cromakalim was reduced significantly. This coronary dynamic profile indicates that both nitrovasodilators and nicorandil directly dilate large coronary vessels, whereas the effect of cromakalim on these vessels is mediated partially through a flow-dependent mechanism. This suggests that nicorandil mainly dilates large coronary arteries through its nitroglycerin-like properties, whereas its ability to dilate coronary resistance vessels depends mainly on its K(+)-channel opener-like properties.", "contents": "Differential effects of nitrovasodilators, K(+)-channel openers, and nicorandil on large and small coronary arteries in conscious dogs. When administered intravenously to conscious dogs, nicorandil, nitrovasodilators (nitroglycerin and SIN-1), and the K(+)-channel opener cromakalim exhibited marked differential effects on large epicardial and small resistance coronary arteries. Nitrovasodilators markedly increased the left circumflex coronary artery diameter at doses at which coronary resistance was not significantly decreased. In contrast, both cromakalim and nicorandil dilated large and small coronary arteries in the same conditions. When coronary blood flow was held to its control value by partial inflation of a hydraulic occluder implanted around the artery, the nitroglycerin- and nicorandil-induced increases in large coronary diameter remained unchanged whereas the response to cromakalim was reduced significantly. This coronary dynamic profile indicates that both nitrovasodilators and nicorandil directly dilate large coronary vessels, whereas the effect of cromakalim on these vessels is mediated partially through a flow-dependent mechanism. This suggests that nicorandil mainly dilates large coronary arteries through its nitroglycerin-like properties, whereas its ability to dilate coronary resistance vessels depends mainly on its K(+)-channel opener-like properties."} {"id": "PMID:1282172", "title": "Cardioprotective effects of nicorandil.", "content": "The effects of nicorandil, a nicotinamide nitrate with K(+)-channel-opening activity, was investigated in several models of ischemia-reperfusion injury in conscious and anesthetized dogs or isolated buffer-perfused rat hearts. In several models of reversible ischemic injury (stunned myocardium) in dogs, nicorandil resulted in an enhanced recovery of regional systolic shortening during reperfusion after a single episode of coronary artery occlusion (10-15 min). These beneficial actions of nicorandil were not shared by the nitrovasodilator sodium nitroprusside but were mimicked by the selective K(+)-channel opener EMD 52692. In a model of irreversible ischemia-reperfusion injury (i.e., 2 h of coronary occlusion followed by reperfusion) in anesthetized dogs, nicorandil produced a marked reduction of myocardial infarct size. An equihypotensive dose of the calcium antagonist nifedipine had no significant effect; however, EMD 52692 produced the same reduction in infarct size as had nicorandil. In isolated, perfused rat hearts subjected to 20 min of low-flow (1.0 ml/min) global ischemia followed by 30 min of reperfusion, nicorandil (7 microM) resulted in a significant improvement in the recovery of isovolumic left ventricular minute work during reperfusion compared with untreated hearts. Finally, the results of in vitro experiments indicated that nicorandil (10(-6) to 10(-3) M) produced a concentration-dependent inhibition of superoxide anion free radical production by human and canine neutrophils. The K(+)-channel opener EMD 52692 also inhibited superoxide production in canine neutrophils. These results indicate that nicorandil is a highly efficacious myocardial protective agent in several animal models of reversible or irreversible ischemia-reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Cardioprotective effects of nicorandil. The effects of nicorandil, a nicotinamide nitrate with K(+)-channel-opening activity, was investigated in several models of ischemia-reperfusion injury in conscious and anesthetized dogs or isolated buffer-perfused rat hearts. In several models of reversible ischemic injury (stunned myocardium) in dogs, nicorandil resulted in an enhanced recovery of regional systolic shortening during reperfusion after a single episode of coronary artery occlusion (10-15 min). These beneficial actions of nicorandil were not shared by the nitrovasodilator sodium nitroprusside but were mimicked by the selective K(+)-channel opener EMD 52692. In a model of irreversible ischemia-reperfusion injury (i.e., 2 h of coronary occlusion followed by reperfusion) in anesthetized dogs, nicorandil produced a marked reduction of myocardial infarct size. An equihypotensive dose of the calcium antagonist nifedipine had no significant effect; however, EMD 52692 produced the same reduction in infarct size as had nicorandil. In isolated, perfused rat hearts subjected to 20 min of low-flow (1.0 ml/min) global ischemia followed by 30 min of reperfusion, nicorandil (7 microM) resulted in a significant improvement in the recovery of isovolumic left ventricular minute work during reperfusion compared with untreated hearts. Finally, the results of in vitro experiments indicated that nicorandil (10(-6) to 10(-3) M) produced a concentration-dependent inhibition of superoxide anion free radical production by human and canine neutrophils. The K(+)-channel opener EMD 52692 also inhibited superoxide production in canine neutrophils. These results indicate that nicorandil is a highly efficacious myocardial protective agent in several animal models of reversible or irreversible ischemia-reperfusion injury.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282173", "title": "Effects of long-term nicorandil application on coronary arteries in conscious dogs.", "content": "Nicorandil acting as both nitrovasodilator and K(+)-channel opener was analyzed with regard to its dilator activity in large coronary arteries. In addition, it was tested for potential development of tolerance in six chronically instrumented conscious dogs that received a 5-day continuous i.v. infusion. Increasing dosages of nicorandil (3, 10, and 30 micrograms.kg-1.min-1) caused dose-dependent strong increases in left circumflex coronary artery diameter (1.3 +/- 0.4%, 5.3 +/- 2.2%, and 8.4 +/- 2.8% above control, respectively). However, 100 micrograms.kg-1.min-1 nicorandil produced substantial hypotension, reflex tachycardia, and reduction of the dilator response in large coronary arteries. During long-term nicorandil administration (10 micrograms.kg-1.min-1 i.v. for 5 days), the diameter of the left circumflex coronary artery was increased by 8.8 +/- 2.5%. This was accompanied by a decrease in mean arterial pressure of 13.3 +/- 6.4% and an increase in heart rate by 41.5 +/- 21.0% compared with controls. On the fifth day of continuous nicorandil infusion, dose-response relations for both nicorandil- and nitroglycerin-induced epicardial artery dilations were shifted to 3.5-fold higher doses. We conclude that nicorandil dilates large coronary arteries in dogs, long-term nicorandil administration does not cause a development of tolerance, long-term nicorandil administration is not associated with the development of cross-tolerance to nitroglycerin, and the small shift of the dose-response relations is considered to reflect a hemodynamic adaptation process due to long-term nicorandil exposure.", "contents": "Effects of long-term nicorandil application on coronary arteries in conscious dogs. Nicorandil acting as both nitrovasodilator and K(+)-channel opener was analyzed with regard to its dilator activity in large coronary arteries. In addition, it was tested for potential development of tolerance in six chronically instrumented conscious dogs that received a 5-day continuous i.v. infusion. Increasing dosages of nicorandil (3, 10, and 30 micrograms.kg-1.min-1) caused dose-dependent strong increases in left circumflex coronary artery diameter (1.3 +/- 0.4%, 5.3 +/- 2.2%, and 8.4 +/- 2.8% above control, respectively). However, 100 micrograms.kg-1.min-1 nicorandil produced substantial hypotension, reflex tachycardia, and reduction of the dilator response in large coronary arteries. During long-term nicorandil administration (10 micrograms.kg-1.min-1 i.v. for 5 days), the diameter of the left circumflex coronary artery was increased by 8.8 +/- 2.5%. This was accompanied by a decrease in mean arterial pressure of 13.3 +/- 6.4% and an increase in heart rate by 41.5 +/- 21.0% compared with controls. On the fifth day of continuous nicorandil infusion, dose-response relations for both nicorandil- and nitroglycerin-induced epicardial artery dilations were shifted to 3.5-fold higher doses. We conclude that nicorandil dilates large coronary arteries in dogs, long-term nicorandil administration does not cause a development of tolerance, long-term nicorandil administration is not associated with the development of cross-tolerance to nitroglycerin, and the small shift of the dose-response relations is considered to reflect a hemodynamic adaptation process due to long-term nicorandil exposure."} {"id": "PMID:1282174", "title": "Pharmacokinetic profile of nicorandil in humans: an overview.", "content": "Nicorandil is rapidly and almost completely absorbed from the gastrointestinal tract. Nicorandil is not metabolized significantly by the liver during passage through the portal system (lack of first-pass effect). Thus, it easily enters the systemic blood flow, resulting in almost complete bioavailability (75-100%). The concomitant food intake decreases the rate of absorption of the drug, resulting in a delay of peak plasma concentration, but has little or no effect on maximal plasma concentration or total amount of absorbed nicorandil. After oral administration of a 5-, 10-, 20-, or 40-mg dose, there is a linear relationship between the doses and increases of maximum plasma concentrations and area under the curve, demonstrating that the pharmacokinetics of nicorandil are linear. Steady-state plasma concentrations of nicorandil usually are reached within approximately 96-120 h after continuous dosing (20 mg b.i.d.), probably due to its distribution and metabolism patterns. On average, the Cmax then is approximately 300 ng/ml, which is achieved rapidly within 30 min after drug intake. Nicorandil is bound weakly to human albumin and other plasma proteins (approximately 25%). After oral (and i.v.) administration of the drug, the apparent volume of distribution is approximately 1.0 L/kg body weight. Nicorandil is metabolized extensively, and the major route of elimination is the kidney: Less than 2% of the dose is excreted through the biliary route. As a consequence, the parent drug is excreted poorly in urine (very low renal clearance), whereas 2-nicotinamidoethanol, a pharmacologically inactive denitrated metabolite, is the major nicorandil-related compound excreted in urine. The nicotinamide/nicotinic acid biotransformation pathway contributes to the accumulation of nicorandil and 2-nicotinamidoethanol (denitrated metabolite) during repeated dosing because of the saturable merging of nicotinamide/nicotinic acid derivatives (from the nicorandil metabolism) into the NAD/NADP endogenous pool of coenzymes. The apparent elimination half-life is short (approximately 1 h), and total body clearance is close to 1.15 L/min, which is lower than the liver blood flow. Especially during repeated dosing, a slower elimination process appears that is related to only approximately 10% of the amount of nicorandil found in plasma. Most of the nicorandil metabolites are excreted during the 24-h period after dosing, with the remainder excreted more slowly (as nicotinamide derivatives). The pharmacokinetics of nicorandil are not altered significantly in elderly persons and in patients who have chronic renal impairment or liver insufficiency. Furthermore, its disposition profile is not modified when concomitant drugs such as drug-metabolizing enzyme inducers or inhibitors are given.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Pharmacokinetic profile of nicorandil in humans: an overview. Nicorandil is rapidly and almost completely absorbed from the gastrointestinal tract. Nicorandil is not metabolized significantly by the liver during passage through the portal system (lack of first-pass effect). Thus, it easily enters the systemic blood flow, resulting in almost complete bioavailability (75-100%). The concomitant food intake decreases the rate of absorption of the drug, resulting in a delay of peak plasma concentration, but has little or no effect on maximal plasma concentration or total amount of absorbed nicorandil. After oral administration of a 5-, 10-, 20-, or 40-mg dose, there is a linear relationship between the doses and increases of maximum plasma concentrations and area under the curve, demonstrating that the pharmacokinetics of nicorandil are linear. Steady-state plasma concentrations of nicorandil usually are reached within approximately 96-120 h after continuous dosing (20 mg b.i.d.), probably due to its distribution and metabolism patterns. On average, the Cmax then is approximately 300 ng/ml, which is achieved rapidly within 30 min after drug intake. Nicorandil is bound weakly to human albumin and other plasma proteins (approximately 25%). After oral (and i.v.) administration of the drug, the apparent volume of distribution is approximately 1.0 L/kg body weight. Nicorandil is metabolized extensively, and the major route of elimination is the kidney: Less than 2% of the dose is excreted through the biliary route. As a consequence, the parent drug is excreted poorly in urine (very low renal clearance), whereas 2-nicotinamidoethanol, a pharmacologically inactive denitrated metabolite, is the major nicorandil-related compound excreted in urine. The nicotinamide/nicotinic acid biotransformation pathway contributes to the accumulation of nicorandil and 2-nicotinamidoethanol (denitrated metabolite) during repeated dosing because of the saturable merging of nicotinamide/nicotinic acid derivatives (from the nicorandil metabolism) into the NAD/NADP endogenous pool of coenzymes. The apparent elimination half-life is short (approximately 1 h), and total body clearance is close to 1.15 L/min, which is lower than the liver blood flow. Especially during repeated dosing, a slower elimination process appears that is related to only approximately 10% of the amount of nicorandil found in plasma. Most of the nicorandil metabolites are excreted during the 24-h period after dosing, with the remainder excreted more slowly (as nicotinamide derivatives). The pharmacokinetics of nicorandil are not altered significantly in elderly persons and in patients who have chronic renal impairment or liver insufficiency. Furthermore, its disposition profile is not modified when concomitant drugs such as drug-metabolizing enzyme inducers or inhibitors are given.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282175", "title": "Nicorandil and cardiovascular performance in patients with coronary artery disease.", "content": "To establish the cardiovascular profile of nicorandil in patients with coronary artery disease, we recently conducted three studies at our institution. In two groups of patients undergoing cardiac catheterization, the effects of 20 mg nicorandil sublingually (s.l.) on, first, left ventricular hemodynamics (n = 10) and, second, coronary vasodilatation (n = 11) were investigated. In the first group, despite a significant decrease of 12% in left ventricular systolic pressure, heart rate did not increase significantly after nicorandil. Both left ventricular end-diastolic pressure (-43%) and the time constant of early isovolumic relaxation (-11%) decreased, whereas peak Vce and Vmax increased (+19%) (all significantly). In the second group, as mean aortic pressure decreased (-13%, p < 0.05), coronary sinus blood flow did not change significantly, and calculated coronary vascular resistance tended to decrease (-10%). Myocardial oxygen consumption decreased significantly by 14%. Quantitative coronary angiography confirmed a significant increase in the mean diameter of nonstenotic coronary artery segments (+ 14%, n = 43) and, importantly, in mean obstruction diameter of stenotic segments (+ 14%, n = 7) after s.l. nicorandil. In a third continuing study, the effects of intracoronary (i.c.) nicorandil (6 micrograms/kg) and isosorbide dinitrate (2 mg) on the epicardial coronary arteries were investigated in 10 patients undergoing coronary angioplasty. In nonstenotic coronary artery segments, mean coronary diameter increased significantly after either nicorandil (+ 12%) or isosorbide dinitrate (+ 17%). In stenotic segments, however, where the increase in obstruction diameter (+ 20%) after i.c. nicorandil was significant, the 8% increase of isosorbide dinitrate was not.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Nicorandil and cardiovascular performance in patients with coronary artery disease. To establish the cardiovascular profile of nicorandil in patients with coronary artery disease, we recently conducted three studies at our institution. In two groups of patients undergoing cardiac catheterization, the effects of 20 mg nicorandil sublingually (s.l.) on, first, left ventricular hemodynamics (n = 10) and, second, coronary vasodilatation (n = 11) were investigated. In the first group, despite a significant decrease of 12% in left ventricular systolic pressure, heart rate did not increase significantly after nicorandil. Both left ventricular end-diastolic pressure (-43%) and the time constant of early isovolumic relaxation (-11%) decreased, whereas peak Vce and Vmax increased (+19%) (all significantly). In the second group, as mean aortic pressure decreased (-13%, p < 0.05), coronary sinus blood flow did not change significantly, and calculated coronary vascular resistance tended to decrease (-10%). Myocardial oxygen consumption decreased significantly by 14%. Quantitative coronary angiography confirmed a significant increase in the mean diameter of nonstenotic coronary artery segments (+ 14%, n = 43) and, importantly, in mean obstruction diameter of stenotic segments (+ 14%, n = 7) after s.l. nicorandil. In a third continuing study, the effects of intracoronary (i.c.) nicorandil (6 micrograms/kg) and isosorbide dinitrate (2 mg) on the epicardial coronary arteries were investigated in 10 patients undergoing coronary angioplasty. In nonstenotic coronary artery segments, mean coronary diameter increased significantly after either nicorandil (+ 12%) or isosorbide dinitrate (+ 17%). In stenotic segments, however, where the increase in obstruction diameter (+ 20%) after i.c. nicorandil was significant, the 8% increase of isosorbide dinitrate was not.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282176", "title": "Acute hemodynamic effects of nicorandil in coronary artery disease.", "content": "Nicorandil is a potent vasodilator with antianginal and anti-ischemic properties that acts on both the coronary and the peripheral vascular bed. Because of its dual vasodilatory mechanisms mediated by an increase in cyclic GMP similar to that of nitrates and by a selective increase in the K+ conductance of the smooth muscle cell membrane, nicorandil unloads the right and left ventricles at rest and during exercise. Thus, compared with the classic nitrates, nicorandil is a more balanced vasodilator, i.e., it affects not only the venous capacitance vessels (as predominantly affected by nitrates) but also the arterial resistance vessels. In clinical pharmacologic trials, nicorandil has been administered intravenously (2 to approximately 14 mg) as well as sublingually and orally in single doses of 10-60 mg. In patients with coronary artery disease and impaired left ventricular function, the decrease in preload resulted in a significant improvement of cardiac output. Depending on the doses applied and the patient populations studied, observed decreases in systemic blood pressure were consistent with decreases in peripheral vascular resistance. The effect on heart rate was small, and no influence on atrioventricular conduction could be detected. Nicorandil enhanced exercise capacity in patients with ischemic heart disease. This benefit can be attributed to the reduction in loading of the right and left ventricle as well as to an improvement of regional wall motion abnormalities secondary to the coronary dilatory properties of the drug. Nicorandil appears to be a valuable additive to the antianginal and anti-ischemic management of coronary artery disease.", "contents": "Acute hemodynamic effects of nicorandil in coronary artery disease. Nicorandil is a potent vasodilator with antianginal and anti-ischemic properties that acts on both the coronary and the peripheral vascular bed. Because of its dual vasodilatory mechanisms mediated by an increase in cyclic GMP similar to that of nitrates and by a selective increase in the K+ conductance of the smooth muscle cell membrane, nicorandil unloads the right and left ventricles at rest and during exercise. Thus, compared with the classic nitrates, nicorandil is a more balanced vasodilator, i.e., it affects not only the venous capacitance vessels (as predominantly affected by nitrates) but also the arterial resistance vessels. In clinical pharmacologic trials, nicorandil has been administered intravenously (2 to approximately 14 mg) as well as sublingually and orally in single doses of 10-60 mg. In patients with coronary artery disease and impaired left ventricular function, the decrease in preload resulted in a significant improvement of cardiac output. Depending on the doses applied and the patient populations studied, observed decreases in systemic blood pressure were consistent with decreases in peripheral vascular resistance. The effect on heart rate was small, and no influence on atrioventricular conduction could be detected. Nicorandil enhanced exercise capacity in patients with ischemic heart disease. This benefit can be attributed to the reduction in loading of the right and left ventricle as well as to an improvement of regional wall motion abnormalities secondary to the coronary dilatory properties of the drug. Nicorandil appears to be a valuable additive to the antianginal and anti-ischemic management of coronary artery disease."} {"id": "PMID:1282177", "title": "Venodilatory effects of nicorandil in healthy volunteers.", "content": "The effects of a single dose of nicorandil (40 mg orally) on human dorsal hand veins in vivo were assessed and compared with the effect of nitroglycerin (0.8 mg sublingually). The hand veins had been preconstricted with norepinephrine to approximately one-third of their initial size. We demonstrated that a venous relaxation occurred after administration of nicorandil and nitroglycerin. In the doses studied, the effect was more pronounced and lasted longer after nicorandil. The pharmacodynamic effects of nicorandil in humans may be explained in part by this venous relaxation.", "contents": "Venodilatory effects of nicorandil in healthy volunteers. The effects of a single dose of nicorandil (40 mg orally) on human dorsal hand veins in vivo were assessed and compared with the effect of nitroglycerin (0.8 mg sublingually). The hand veins had been preconstricted with norepinephrine to approximately one-third of their initial size. We demonstrated that a venous relaxation occurred after administration of nicorandil and nitroglycerin. In the doses studied, the effect was more pronounced and lasted longer after nicorandil. The pharmacodynamic effects of nicorandil in humans may be explained in part by this venous relaxation."} {"id": "PMID:1282178", "title": "Efficacy of nicorandil versus propranolol in mild stable angina pectoris of effort: a long-term, double-blind, randomized study.", "content": "Nicorandil is a potent coronary vasodilator. To assess its long-term antianginal effect, we designed a randomized, parallel double-blind trial of 6 weeks' duration comparing nicorandil (10 or 20 mg b.i.d.) with propranolol (40 or 80 mg t.i.d.). The study comprised 77 men with stable angina, no maintenance medication at entry, and an exercise test positive for angina and ST-segment depression. The therapy was started with 10 mg nicorandil b.i.d. or 40 mg propranolol t.i.d. After 3 weeks, the dosage could be doubled according to clinical criteria. Four men receiving nicorandil and one receiving propranolol were withdrawn with side effects; in three cases, the data were not complete. Thus, comparative data were obtained in 69 patients; in 51 of these (26 receiving nicorandil and 25 receiving propranolol), the dosage was increased to the higher level. Blood pressure and heart rate were unaltered by nicorandil and lowered by propranolol. The number of anginal attacks decreased relative to baseline on nicorandil and propranolol (p < 0.002), but total exercise duration was not influenced by either drug. The exercise test performed 2 h after either pill ingestion showed a decrease and a delay in occurrence of myocardial ischemia. The test performed 12 h after medication exhibited reduced ischemia, whereas only propranolol resulted in delayed ST-segment depression. The double product of heart rate and systolic blood pressure was affected only slightly by nicorandil and reduced significantly by propranolol (p < 0.001). Thus, nicorandil medication affords similar improvement as propranolol in patients with angina pectoris, but the mode of action appears to be different.", "contents": "Efficacy of nicorandil versus propranolol in mild stable angina pectoris of effort: a long-term, double-blind, randomized study. Nicorandil is a potent coronary vasodilator. To assess its long-term antianginal effect, we designed a randomized, parallel double-blind trial of 6 weeks' duration comparing nicorandil (10 or 20 mg b.i.d.) with propranolol (40 or 80 mg t.i.d.). The study comprised 77 men with stable angina, no maintenance medication at entry, and an exercise test positive for angina and ST-segment depression. The therapy was started with 10 mg nicorandil b.i.d. or 40 mg propranolol t.i.d. After 3 weeks, the dosage could be doubled according to clinical criteria. Four men receiving nicorandil and one receiving propranolol were withdrawn with side effects; in three cases, the data were not complete. Thus, comparative data were obtained in 69 patients; in 51 of these (26 receiving nicorandil and 25 receiving propranolol), the dosage was increased to the higher level. Blood pressure and heart rate were unaltered by nicorandil and lowered by propranolol. The number of anginal attacks decreased relative to baseline on nicorandil and propranolol (p < 0.002), but total exercise duration was not influenced by either drug. The exercise test performed 2 h after either pill ingestion showed a decrease and a delay in occurrence of myocardial ischemia. The test performed 12 h after medication exhibited reduced ischemia, whereas only propranolol resulted in delayed ST-segment depression. The double product of heart rate and systolic blood pressure was affected only slightly by nicorandil and reduced significantly by propranolol (p < 0.001). Thus, nicorandil medication affords similar improvement as propranolol in patients with angina pectoris, but the mode of action appears to be different."} {"id": "PMID:1282179", "title": "Antianginal and anti-ischemic efficacy of nicorandil compared with nifedipine in patients with angina pectoris and coronary heart disease: a double-blind, randomized, multicenter study.", "content": "Patients with stable, effort-induced angina pectoris and a typical combination of anginal pain and ischemic ST depression in exercise tolerance tests were randomized to treatment for 8 weeks with nicorandil (a newly developed antianginal and anti-ischemic drug) or nifedipine. After 4 weeks, the dosage of nicorandil was increased from 10 mg b.i.d. to 20 mg b.i.d., but the recommended dosage of nifedipine, 20 mg b.i.d., was kept constant during the study period. Double-blind treatment was preceded by a 2-week prephase during which patients were treated with isosorbide dinitrate. During the study period, patients were asked to report the rate of anginal attacks and consumption of sublingual nitroglycerin. Measurements of blood pressure and heart rate at rest and during exercise always were performed 2 h after drug intake. Fifty-eight patients were randomized--29 to nicorandil and 29 to nifedipine. There were large individual variations in anginal attack rates, which makes group comparisons difficult, but in the nicorandil group, the anginal attack rate decreased significantly compared with baseline frequency. Systolic blood pressure at rest was reduced significantly only with the highest dose of nicorandil, but nifedipine had a significant effect on both systolic and diastolic blood pressures as well as on the heart rate. Both treatments significantly increased exercise duration, time to onset of angina pectoris, and time to 1-mm ST depression. In the nicorandil group, an improvement was noted with the 20-mg dose compared with the 10-mg dose, but no significant differences were noted between the nicorandil and nifedipine groups after either 4 or 8 weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Antianginal and anti-ischemic efficacy of nicorandil compared with nifedipine in patients with angina pectoris and coronary heart disease: a double-blind, randomized, multicenter study. Patients with stable, effort-induced angina pectoris and a typical combination of anginal pain and ischemic ST depression in exercise tolerance tests were randomized to treatment for 8 weeks with nicorandil (a newly developed antianginal and anti-ischemic drug) or nifedipine. After 4 weeks, the dosage of nicorandil was increased from 10 mg b.i.d. to 20 mg b.i.d., but the recommended dosage of nifedipine, 20 mg b.i.d., was kept constant during the study period. Double-blind treatment was preceded by a 2-week prephase during which patients were treated with isosorbide dinitrate. During the study period, patients were asked to report the rate of anginal attacks and consumption of sublingual nitroglycerin. Measurements of blood pressure and heart rate at rest and during exercise always were performed 2 h after drug intake. Fifty-eight patients were randomized--29 to nicorandil and 29 to nifedipine. There were large individual variations in anginal attack rates, which makes group comparisons difficult, but in the nicorandil group, the anginal attack rate decreased significantly compared with baseline frequency. Systolic blood pressure at rest was reduced significantly only with the highest dose of nicorandil, but nifedipine had a significant effect on both systolic and diastolic blood pressures as well as on the heart rate. Both treatments significantly increased exercise duration, time to onset of angina pectoris, and time to 1-mm ST depression. In the nicorandil group, an improvement was noted with the 20-mg dose compared with the 10-mg dose, but no significant differences were noted between the nicorandil and nifedipine groups after either 4 or 8 weeks of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282180", "title": "Antianginal and anti-ischemic efficacy of nicorandil in comparison with isosorbide-5-mononitrate and isosorbide dinitrate: results from two multicenter, double-blind, randomized studies with stable coronary heart disease patients.", "content": "The purpose of the two double-blind studies summarized in this article was to compare the antianginal and anti-ischemic effects of nicorandil with those of two different nitrate preparations. A total of 129 patients with stable New York Heart Association functional class II or III coronary heart disease were enrolled in the studies. Ninety-five patients received nicorandil, 34 received isosorbide dinitrate (ISDN), and 63 received isosorbide-5-mononitrate (MN). In study 1, nicorandil was compared with MN in a crossover design with 54 protocols eligible for efficacy assessment of MN and 52 eligible for nicorandil, respectively. Twenty milligrams of nicorandil and 20 mg MN administered b.i.d. for 4 weeks were equally effective in the treatment of stress-induced angina. Both drugs prolonged bicycle exercise tolerance and reduced weekly anginal attack rates. In study 2, nicorandil and ISDN were administered to two parallel groups of patients at a dose of 10 mg t.i.d. for 2 weeks and then 20 mg t.i.d. for 4 weeks. Under the assumption that the repetitive administration of nitrates with short dosing intervals might induce the development of tolerance to the nitrate mechanism of action, the t.i.d.-dosing regimen had been chosen in this study. Thirty-two protocols from those receiving nicorandil and 34 protocols from those receiving ISDN were eligible for efficacy assessment. Both drugs increased exercise capacity and reduced ST-segment depression at identical work loads with no significant difference between groups (p > 0.05). For both drugs, the higher doses were more effective than the lower doses. tolerance to the nitrate mechanism of action did not develop with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Antianginal and anti-ischemic efficacy of nicorandil in comparison with isosorbide-5-mononitrate and isosorbide dinitrate: results from two multicenter, double-blind, randomized studies with stable coronary heart disease patients. The purpose of the two double-blind studies summarized in this article was to compare the antianginal and anti-ischemic effects of nicorandil with those of two different nitrate preparations. A total of 129 patients with stable New York Heart Association functional class II or III coronary heart disease were enrolled in the studies. Ninety-five patients received nicorandil, 34 received isosorbide dinitrate (ISDN), and 63 received isosorbide-5-mononitrate (MN). In study 1, nicorandil was compared with MN in a crossover design with 54 protocols eligible for efficacy assessment of MN and 52 eligible for nicorandil, respectively. Twenty milligrams of nicorandil and 20 mg MN administered b.i.d. for 4 weeks were equally effective in the treatment of stress-induced angina. Both drugs prolonged bicycle exercise tolerance and reduced weekly anginal attack rates. In study 2, nicorandil and ISDN were administered to two parallel groups of patients at a dose of 10 mg t.i.d. for 2 weeks and then 20 mg t.i.d. for 4 weeks. Under the assumption that the repetitive administration of nitrates with short dosing intervals might induce the development of tolerance to the nitrate mechanism of action, the t.i.d.-dosing regimen had been chosen in this study. Thirty-two protocols from those receiving nicorandil and 34 protocols from those receiving ISDN were eligible for efficacy assessment. Both drugs increased exercise capacity and reduced ST-segment depression at identical work loads with no significant difference between groups (p > 0.05). For both drugs, the higher doses were more effective than the lower doses. tolerance to the nitrate mechanism of action did not develop with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282181", "title": "Pharmacological characterization of nicorandil by 86Rb efflux and isometric vasorelaxation studies in vascular smooth muscle.", "content": "Nicorandil and cromakalim were found to stimulate 86Rb efflux (a marker of K+ ions) from resting preparations of rabbit aorta. This action was suppressed by 10(-5) M glibenclamide, an antagonist of K(+)-channel openers in vascular smooth muscle. Through intracellular production of cyclic GMP, and subsequent suppression of cellular Ca2+ activation, nitrovasodilators interfere indirectly with the activation of Ca(2+)-dependent ion channels. 8-Bromo-cyclic GMP and sodium nitroprusside antagonized the Ca(2+)-dependent 86Rb efflux induced by 3 x 10(-7) M norepinephrine. When nicorandil and cromakalim were investigated in the same experimental setup in the presence of glibenclamide to suppress stimulation of K+ channels, only nicorandil also suppressed the norepinephrine-induced increase of the 86Rb efflux. These results confirm that nicorandil acts as both an opener of K+ channels and a nitrovasodilator. Nicorandil relaxed helical strips from rabbit aorta contracted by 10(-7) M norepinephrine, but in contrast to the relaxant action of cromakalim, this response was not antagonized by the use of glibenclamide, indicating a greater importance of the nitrovasodilator mechanism than of the K(+)-channel-opening activity for relaxation in this tissue. However, when the nitrate-like action of nicorandil was suppressed by 10(-5) M methylene blue, the K(+)-channel-opening activity was unmasked on addition of 10(-4) M glibenclamide at high concentrations of nicorandil.", "contents": "Pharmacological characterization of nicorandil by 86Rb efflux and isometric vasorelaxation studies in vascular smooth muscle. Nicorandil and cromakalim were found to stimulate 86Rb efflux (a marker of K+ ions) from resting preparations of rabbit aorta. This action was suppressed by 10(-5) M glibenclamide, an antagonist of K(+)-channel openers in vascular smooth muscle. Through intracellular production of cyclic GMP, and subsequent suppression of cellular Ca2+ activation, nitrovasodilators interfere indirectly with the activation of Ca(2+)-dependent ion channels. 8-Bromo-cyclic GMP and sodium nitroprusside antagonized the Ca(2+)-dependent 86Rb efflux induced by 3 x 10(-7) M norepinephrine. When nicorandil and cromakalim were investigated in the same experimental setup in the presence of glibenclamide to suppress stimulation of K+ channels, only nicorandil also suppressed the norepinephrine-induced increase of the 86Rb efflux. These results confirm that nicorandil acts as both an opener of K+ channels and a nitrovasodilator. Nicorandil relaxed helical strips from rabbit aorta contracted by 10(-7) M norepinephrine, but in contrast to the relaxant action of cromakalim, this response was not antagonized by the use of glibenclamide, indicating a greater importance of the nitrovasodilator mechanism than of the K(+)-channel-opening activity for relaxation in this tissue. However, when the nitrate-like action of nicorandil was suppressed by 10(-5) M methylene blue, the K(+)-channel-opening activity was unmasked on addition of 10(-4) M glibenclamide at high concentrations of nicorandil."} {"id": "PMID:1282182", "title": "Prevention of coronary spasm by nicorandil: comparison with nifedipine.", "content": "The efficacy of nicorandil was compared with that of nifedipine in 13 patients with vasospastic angina enrolled in a randomized, placebo-controlled, crossover study. All patients had a coronary spasm during coronary arteriography, either spontaneously or ergometrine-induced. During two consecutive periods of 2 days, patients received active drugs or placebo in a randomized order. Each patient received single oral doses of 30 mg nicorandil, 10 mg nifedipine, and, on 2 days, a placebo. One hour after drug intake, patients underwent an ergometrine test with increasing doses of Methergin (ergometrine) (0.05, 0.10, 0.20, and 0.40 mg every 5 min). After placebo, the tests always were positive, and the ECG changes occurred at the same +/- 1 dose of ergometrine in 10 cases, showing good reproducibility. After nicorandil, the tests were negative in nine patients and positive for a higher or lower dose of ergometrine in three and one patient, respectively (p = 0.0034 vs. placebo). After nifedipine, the tests were negative in five patients and positive for a higher or the same dose of ergometrine in four and four patients, respectively (p = 0.0039 vs. placebo). Nifedipine (10 mg) and nicorandil (30 mg) were equally effective in eight patients; in the remaining five patients, nicorandil had better results (p = 0.06). Nicorandil (30 mg) prevents ergometrine-induced coronary spasm. This compound may be beneficial in patients with vasospastic angina.", "contents": "Prevention of coronary spasm by nicorandil: comparison with nifedipine. The efficacy of nicorandil was compared with that of nifedipine in 13 patients with vasospastic angina enrolled in a randomized, placebo-controlled, crossover study. All patients had a coronary spasm during coronary arteriography, either spontaneously or ergometrine-induced. During two consecutive periods of 2 days, patients received active drugs or placebo in a randomized order. Each patient received single oral doses of 30 mg nicorandil, 10 mg nifedipine, and, on 2 days, a placebo. One hour after drug intake, patients underwent an ergometrine test with increasing doses of Methergin (ergometrine) (0.05, 0.10, 0.20, and 0.40 mg every 5 min). After placebo, the tests always were positive, and the ECG changes occurred at the same +/- 1 dose of ergometrine in 10 cases, showing good reproducibility. After nicorandil, the tests were negative in nine patients and positive for a higher or lower dose of ergometrine in three and one patient, respectively (p = 0.0034 vs. placebo). After nifedipine, the tests were negative in five patients and positive for a higher or the same dose of ergometrine in four and four patients, respectively (p = 0.0039 vs. placebo). Nifedipine (10 mg) and nicorandil (30 mg) were equally effective in eight patients; in the remaining five patients, nicorandil had better results (p = 0.06). Nicorandil (30 mg) prevents ergometrine-induced coronary spasm. This compound may be beneficial in patients with vasospastic angina."} {"id": "PMID:1282183", "title": "Selected issues from an overview on nicorandil: tolerance, duration of action, and long-term efficacy.", "content": "Nicorandil exerts its pharmacodynamic effects through two different modes of action: increase of cyclic GMP and activation of K+ channels of smooth muscle cells. The latter mechanism could explain the lack of development of tolerance that had been demonstrated clearly in various animal experiments. Therefore, it was attempted to elucidate this mechanism in humans. In 16 healthy subjects, the acute hemodynamic effects of a single oral dose of 40 mg nicorandil were compared with those of a single sublingual dose of 0.8 mg nitroglycerin. Thereafter, the subjects were treated with 30 mg isosorbide-5-mononitrate (IS-5-MN) slow release t.i.d. for 7 days to induce nitrate tolerance. Two hours after the last dose of IS-5-MN, hemodynamic measurements were repeated before and after administration of nicorandil and nitroglycerin, respectively. Recordings obtained from impedance cardiography and finger plethysmography as well as measurements of systolic time intervals provided evidence that nicorandil in the state of IS-5-MN tolerance continued to exert hemodynamic effects similar to those exerted after the first dose. The hemodynamic actions of nitroglycerin were no longer observed after chronic treatment with IS-5-MN. The duration of action of nicorandil was investigated in 22 patients with coronary artery disease (CAD). After a 2-week run-in period on placebo, patients had to perform a symptom-limited bicycle exercise tolerance test (ETT) on two separate days in which the reproducible anginal threshold had to be proven. After qualification, patients were allocated randomly to receive double-blind 10 or 20 mg nicorandil b.i.d. for 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Selected issues from an overview on nicorandil: tolerance, duration of action, and long-term efficacy. Nicorandil exerts its pharmacodynamic effects through two different modes of action: increase of cyclic GMP and activation of K+ channels of smooth muscle cells. The latter mechanism could explain the lack of development of tolerance that had been demonstrated clearly in various animal experiments. Therefore, it was attempted to elucidate this mechanism in humans. In 16 healthy subjects, the acute hemodynamic effects of a single oral dose of 40 mg nicorandil were compared with those of a single sublingual dose of 0.8 mg nitroglycerin. Thereafter, the subjects were treated with 30 mg isosorbide-5-mononitrate (IS-5-MN) slow release t.i.d. for 7 days to induce nitrate tolerance. Two hours after the last dose of IS-5-MN, hemodynamic measurements were repeated before and after administration of nicorandil and nitroglycerin, respectively. Recordings obtained from impedance cardiography and finger plethysmography as well as measurements of systolic time intervals provided evidence that nicorandil in the state of IS-5-MN tolerance continued to exert hemodynamic effects similar to those exerted after the first dose. The hemodynamic actions of nitroglycerin were no longer observed after chronic treatment with IS-5-MN. The duration of action of nicorandil was investigated in 22 patients with coronary artery disease (CAD). After a 2-week run-in period on placebo, patients had to perform a symptom-limited bicycle exercise tolerance test (ETT) on two separate days in which the reproducible anginal threshold had to be proven. After qualification, patients were allocated randomly to receive double-blind 10 or 20 mg nicorandil b.i.d. for 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282184", "title": "Clinical profile of nicorandil: an overview of its hemodynamic properties and therapeutic efficacy.", "content": "Nicorandil is a new vasodilator agent. Efficacy and safety of nicorandil in the treatment of angina pectoris have been evaluated through an extensive clinical program with a total of 1,680 patients who received the product. Results of hemodynamic studies provide clear evidence of the vasodilatory effect of nicorandil. In a population of patients with normal left ventricular function, a reduction in preload was apparent from a decrease in left ventricular end-diastolic pressure from 7.4 +/- 1.7 to -3.2 +/- 1.5 mm Hg. Furthermore, nicorandil produced marked reductions in total peripheral resistance (19%) and aortic blood pressures with decreases in systolic pressure of 34% and in diastolic pressure of 21%. At antianginal doses, nicorandil has a coronary vasodilating effect as well as a balanced peripheral action that leads to decreases in both preload and afterload. Therefore, nicorandil affects two of the main hemodynamic determinants of oxygen demand without impairing myocardial contractility or atrioventricular conduction. In addition, its strong spasmolytic activity is of particular interest when dynamic coronary obstruction is considered. Nicorandil clearly has demonstrated K(+)-channel-opening activity. In addition, the range of plasma concentrations in humans at therapeutic doses is similar to that of experimental models in which the K(+)-channel activity has been determined. This mechanism of action may explain the different hemodynamic profiles of nicorandil and nitrates in humans. Nicorandil is an effective and potent antianginal agent at a dose of 10-40 mg, which in monotherapy controls 69-80% of patients with stable chronic angina. Comparative trials have shown that the efficacy of nicorandil compares with that of drugs from the main classes of antianginal drugs--beta-blockers (atenolol, propranolol) and a Ca2+ antagonist (diltiazem). Patients treated for as long as 3 months or 1 year have shown sustained efficacy with no evidence of development of tolerance to the drug. The long duration of action allows effective treatment with a well-tolerated b.i.d. regimen. At the recommended doses, the main side effects were limited to headaches. They usually occurred early in the course of treatment and can be diminished by a progressive titration. From the large safety data base, there is no evidence that nicorandil induced exacerbation of myocardial ischemia or abrupt withdrawal syndrome. Nicorandil does not adversely affect the lipid profile or the glucose level. As an antianginal drug with a novel mechanism of action, nicorandil provides a useful alternative to existing antianginal agents in the long-term management of patients with angina pectoris.", "contents": "Clinical profile of nicorandil: an overview of its hemodynamic properties and therapeutic efficacy. Nicorandil is a new vasodilator agent. Efficacy and safety of nicorandil in the treatment of angina pectoris have been evaluated through an extensive clinical program with a total of 1,680 patients who received the product. Results of hemodynamic studies provide clear evidence of the vasodilatory effect of nicorandil. In a population of patients with normal left ventricular function, a reduction in preload was apparent from a decrease in left ventricular end-diastolic pressure from 7.4 +/- 1.7 to -3.2 +/- 1.5 mm Hg. Furthermore, nicorandil produced marked reductions in total peripheral resistance (19%) and aortic blood pressures with decreases in systolic pressure of 34% and in diastolic pressure of 21%. At antianginal doses, nicorandil has a coronary vasodilating effect as well as a balanced peripheral action that leads to decreases in both preload and afterload. Therefore, nicorandil affects two of the main hemodynamic determinants of oxygen demand without impairing myocardial contractility or atrioventricular conduction. In addition, its strong spasmolytic activity is of particular interest when dynamic coronary obstruction is considered. Nicorandil clearly has demonstrated K(+)-channel-opening activity. In addition, the range of plasma concentrations in humans at therapeutic doses is similar to that of experimental models in which the K(+)-channel activity has been determined. This mechanism of action may explain the different hemodynamic profiles of nicorandil and nitrates in humans. Nicorandil is an effective and potent antianginal agent at a dose of 10-40 mg, which in monotherapy controls 69-80% of patients with stable chronic angina. Comparative trials have shown that the efficacy of nicorandil compares with that of drugs from the main classes of antianginal drugs--beta-blockers (atenolol, propranolol) and a Ca2+ antagonist (diltiazem). Patients treated for as long as 3 months or 1 year have shown sustained efficacy with no evidence of development of tolerance to the drug. The long duration of action allows effective treatment with a well-tolerated b.i.d. regimen. At the recommended doses, the main side effects were limited to headaches. They usually occurred early in the course of treatment and can be diminished by a progressive titration. From the large safety data base, there is no evidence that nicorandil induced exacerbation of myocardial ischemia or abrupt withdrawal syndrome. Nicorandil does not adversely affect the lipid profile or the glucose level. As an antianginal drug with a novel mechanism of action, nicorandil provides a useful alternative to existing antianginal agents in the long-term management of patients with angina pectoris."} {"id": "PMID:1282185", "title": "Electromagnetic gating in ion channels.", "content": "There have been many attempts to develop a theoretical explanation of the phenomena of electromagnetic field interactions with biological systems. None of the reported efforts have been entirely successful in accounting for the observed experimental results, in particular with respect to the reports of interactions between extremely low frequency (ELF) magnetic fields and biological systems at ion cyclotron resonance frequencies. The approach used in this paper starts with the Lorentz force equation, but use is made of cylindrical co-ordinates and cylindrical boundary conditions in an attempt to more closely model the walls of an ion channel. The equations of motion of an ion that result from this approach suggest that the inside shape of the channel plus the ELF magnetic fields at specific frequencies and amplitudes could act as a gate to control the movement of the ion across the cell membrane.", "contents": "Electromagnetic gating in ion channels. There have been many attempts to develop a theoretical explanation of the phenomena of electromagnetic field interactions with biological systems. None of the reported efforts have been entirely successful in accounting for the observed experimental results, in particular with respect to the reports of interactions between extremely low frequency (ELF) magnetic fields and biological systems at ion cyclotron resonance frequencies. The approach used in this paper starts with the Lorentz force equation, but use is made of cylindrical co-ordinates and cylindrical boundary conditions in an attempt to more closely model the walls of an ion channel. The equations of motion of an ion that result from this approach suggest that the inside shape of the channel plus the ELF magnetic fields at specific frequencies and amplitudes could act as a gate to control the movement of the ion across the cell membrane."} {"id": "PMID:1282186", "title": "Self-replication of chemical systems based on recognition within a double or a triple helix: a realistic hypothesis.", "content": "A scenario is proposed by which non-enzymatic self-replication of short RNA molecules could occur. The hypothesis is illustrated for the self-replication of an oligopyrimidine (Y) strand. The successful replication of Y requires a series of plausible steps. The first, experimentally feasible, step involves the template-directed polynucleotide synthesis, based on Watson-Crick base pairing, of an oligopurine (R) strand using Y as the template, and chemically activated mononucleotides as the building blocks. This step will result in the formation of an oligopyrimidine.oligopurine (YR) double helix. The second step requires the use of the double helix as the template for the synthesis of a second oligopyrimidine (Y') strand from activated pyrimidine monomers. This synthesis could be facilitated by the binding of the monopyrimidines in the major groove of the YR double helix, via Hoogsteen-type base pairing with the R strand, establishing in that sense triple helix recognition. This step, if successful, should result in the formation of a new strand, Y', that runs parallel to the oligopurine strand. Y' differs from Y in that all 3'-5' phosphodiester linkages in Y are replaced by 5'-3' linkages in Y'. The resulting triple helix (YRY') is in dynamic equilibrium with YR and free Y'. In subsequent steps, unassociated Y' directs the synthesis of the complementary oligopurine (R') strand forming a new double helix Y'R' that may direct the synthesis of an oligopyrimidine strand, Y, that is expected to be identical to the first strand that started the whole sequence. An attempt is made to generalize the above hypothesis to mixed oligonucleotides containing all four bases and identify the limitations of this hypothesis.", "contents": "Self-replication of chemical systems based on recognition within a double or a triple helix: a realistic hypothesis. A scenario is proposed by which non-enzymatic self-replication of short RNA molecules could occur. The hypothesis is illustrated for the self-replication of an oligopyrimidine (Y) strand. The successful replication of Y requires a series of plausible steps. The first, experimentally feasible, step involves the template-directed polynucleotide synthesis, based on Watson-Crick base pairing, of an oligopurine (R) strand using Y as the template, and chemically activated mononucleotides as the building blocks. This step will result in the formation of an oligopyrimidine.oligopurine (YR) double helix. The second step requires the use of the double helix as the template for the synthesis of a second oligopyrimidine (Y') strand from activated pyrimidine monomers. This synthesis could be facilitated by the binding of the monopyrimidines in the major groove of the YR double helix, via Hoogsteen-type base pairing with the R strand, establishing in that sense triple helix recognition. This step, if successful, should result in the formation of a new strand, Y', that runs parallel to the oligopurine strand. Y' differs from Y in that all 3'-5' phosphodiester linkages in Y are replaced by 5'-3' linkages in Y'. The resulting triple helix (YRY') is in dynamic equilibrium with YR and free Y'. In subsequent steps, unassociated Y' directs the synthesis of the complementary oligopurine (R') strand forming a new double helix Y'R' that may direct the synthesis of an oligopyrimidine strand, Y, that is expected to be identical to the first strand that started the whole sequence. An attempt is made to generalize the above hypothesis to mixed oligonucleotides containing all four bases and identify the limitations of this hypothesis."} {"id": "PMID:1282187", "title": "A method for fixation of previously fresh-frozen human adult and fetal brains that preserves histological quality and immunoreactivity.", "content": "A method is described that enables fixation of previously fresh-frozen and stored adult and fetal human or animal brains. The method involves fixing during thawing under controlled, cryoprotected conditions and is compatible with good histological quality and the preservation of enzymatic activity and immunoreactivity of many neural antigens. It offers considerable advantages for the storage of large amounts of tissue from which multiple samples can be taken and processed under fixation and other conditions that can be optimized for a variety of methods, many of which may be incompatible if the whole brain is fixed in a single fixative prior to storage.", "contents": "A method for fixation of previously fresh-frozen human adult and fetal brains that preserves histological quality and immunoreactivity. A method is described that enables fixation of previously fresh-frozen and stored adult and fetal human or animal brains. The method involves fixing during thawing under controlled, cryoprotected conditions and is compatible with good histological quality and the preservation of enzymatic activity and immunoreactivity of many neural antigens. It offers considerable advantages for the storage of large amounts of tissue from which multiple samples can be taken and processed under fixation and other conditions that can be optimized for a variety of methods, many of which may be incompatible if the whole brain is fixed in a single fixative prior to storage."} {"id": "PMID:1282188", "title": "The use of texture analysis for the discrimination of Nissl substance in neurons.", "content": "Structural changes induced by cordotomy in the Nissl substance of identifiable spinal motoneurons innervating the white musculature of the European eel were quantified with the use of texture features calculated from digitized images. Data were evaluated and the motoneurons classified by using multivariate analysis. The study shows that there are differences in the structural organization of the Nissl substance of motoneurons taken from control and cordotomized fishes. Distinction could only be made by using texture features, as visual examination of the motoneurons did not reveal any alteration of the studied cellular substance. Reorganization of the Nissl substance might be the result of a changed protein metabolism or a changed neuronal activity pattern consequent upon cordotomy. The method employs quick and simple techniques and could be useful in several other neurobiological studies.", "contents": "The use of texture analysis for the discrimination of Nissl substance in neurons. Structural changes induced by cordotomy in the Nissl substance of identifiable spinal motoneurons innervating the white musculature of the European eel were quantified with the use of texture features calculated from digitized images. Data were evaluated and the motoneurons classified by using multivariate analysis. The study shows that there are differences in the structural organization of the Nissl substance of motoneurons taken from control and cordotomized fishes. Distinction could only be made by using texture features, as visual examination of the motoneurons did not reveal any alteration of the studied cellular substance. Reorganization of the Nissl substance might be the result of a changed protein metabolism or a changed neuronal activity pattern consequent upon cordotomy. The method employs quick and simple techniques and could be useful in several other neurobiological studies."} {"id": "PMID:1282189", "title": "Clinical potency of calcium channel blockers in asthma may be related to their inhibition of receptor-mediated phasic responses in vitro.", "content": "The calcium channel blockers (CCB) have been clinically effective in exercise-induced asthma. The completeness of protection with the CCB might be related specifically to inhibition of Ca2+ influx or release. To examine this hypothesis, the rank order of potency of inhibition of the CCB, nicardipine, diltiazem and verapamil on the steady-state and kinetic parameters of the phasic and tonic responses to the muscarinic receptor agonist carbachol (10 microM) and KCl (40 mM) in the intact isolated guinea-pig trachea was determined. The Ca2+ channel agonist Bay K 8644 was also examined for its effects on intracellular Ca2+. Nicardipine abolished the KCl response at both 0.1 microM and 1 microM concentrations. The amplitude of the KCl response was inhibited equally by 1 microM diltiazem (61% inhibition) and 1 microM verapamil (68% inhibition). The rate constant of onset of the KCl response was similarly inhibited 60% by diltiazem and 66% by verapamil. Nicardipine abolished the carbachol phasic response at the 1 microM concentration. The amplitude of the phasic response was inhibited equally by 0.1 microM nicardipine (61.3% inhibition), 1 microM diltiazem (64.5% inhibition) and 1 microM verapamil (71% inhibition). The rate constant of decay of the phasic response was inhibited equally by 0.1 microM nicardipine (43% inhibition) and 1 microM diltiazem (29% inhibition). The rate constant of onset of the phasic response was unaffected by nicardipine, diltiazem and verapamil. Only 1 microM nicardipine inhibited the amplitude and rate constant of onset of the tonic response. The only effect of Bay K 8644 (1 microM) was to increase the phasic response amplitude. The CCB demonstrate a similar order of potency for inhibition of the phasic responses and clinical efficacy of the CCB in exercise-induced asthma (nicardipine > verapamil > diltiazem).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Clinical potency of calcium channel blockers in asthma may be related to their inhibition of receptor-mediated phasic responses in vitro. The calcium channel blockers (CCB) have been clinically effective in exercise-induced asthma. The completeness of protection with the CCB might be related specifically to inhibition of Ca2+ influx or release. To examine this hypothesis, the rank order of potency of inhibition of the CCB, nicardipine, diltiazem and verapamil on the steady-state and kinetic parameters of the phasic and tonic responses to the muscarinic receptor agonist carbachol (10 microM) and KCl (40 mM) in the intact isolated guinea-pig trachea was determined. The Ca2+ channel agonist Bay K 8644 was also examined for its effects on intracellular Ca2+. Nicardipine abolished the KCl response at both 0.1 microM and 1 microM concentrations. The amplitude of the KCl response was inhibited equally by 1 microM diltiazem (61% inhibition) and 1 microM verapamil (68% inhibition). The rate constant of onset of the KCl response was similarly inhibited 60% by diltiazem and 66% by verapamil. Nicardipine abolished the carbachol phasic response at the 1 microM concentration. The amplitude of the phasic response was inhibited equally by 0.1 microM nicardipine (61.3% inhibition), 1 microM diltiazem (64.5% inhibition) and 1 microM verapamil (71% inhibition). The rate constant of decay of the phasic response was inhibited equally by 0.1 microM nicardipine (43% inhibition) and 1 microM diltiazem (29% inhibition). The rate constant of onset of the phasic response was unaffected by nicardipine, diltiazem and verapamil. Only 1 microM nicardipine inhibited the amplitude and rate constant of onset of the tonic response. The only effect of Bay K 8644 (1 microM) was to increase the phasic response amplitude. The CCB demonstrate a similar order of potency for inhibition of the phasic responses and clinical efficacy of the CCB in exercise-induced asthma (nicardipine > verapamil > diltiazem).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282190", "title": "Thalidomide and the immune system. 2. Changes in receptors on blood cells of a healthy volunteer.", "content": "Thalidomide (Thd) was given in two trials (total daily dose: 5 or 8 mg Thd/kg body weight, respectively) for five and three days to a healthy male volunteer, and various receptors were analyzed on white blood cells before, during and after (up to 30 days) the treatment period. There were neither marked deviations in the absolute number of total leukocytes nor in the percentage of total lymphocytes or monocytes throughout the study period. The most pronounced changes were observed in the surface receptors on CD4 (\"helper cells\") cells and leukocytes bearing the CD11b (Mac 1) and other integrin and adhesion receptors. Other changes included shifts in the ratio cytotoxic cells/suppressor cells as well as a reduction of the receptor density (passage from bright to dim) in T helper cells bearing CD45RO \"memory\" markers. Simultaneously, the number of B cells was found to be increased as was the percentage of some adhesion receptors on CD8+ cells. Unlike in previous experiments in which Thd was administered to marmoset monkeys, no effect could be seen in cells bearing the CD2 (LFA-2) epitope.", "contents": "Thalidomide and the immune system. 2. Changes in receptors on blood cells of a healthy volunteer. Thalidomide (Thd) was given in two trials (total daily dose: 5 or 8 mg Thd/kg body weight, respectively) for five and three days to a healthy male volunteer, and various receptors were analyzed on white blood cells before, during and after (up to 30 days) the treatment period. There were neither marked deviations in the absolute number of total leukocytes nor in the percentage of total lymphocytes or monocytes throughout the study period. The most pronounced changes were observed in the surface receptors on CD4 (\"helper cells\") cells and leukocytes bearing the CD11b (Mac 1) and other integrin and adhesion receptors. Other changes included shifts in the ratio cytotoxic cells/suppressor cells as well as a reduction of the receptor density (passage from bright to dim) in T helper cells bearing CD45RO \"memory\" markers. Simultaneously, the number of B cells was found to be increased as was the percentage of some adhesion receptors on CD8+ cells. Unlike in previous experiments in which Thd was administered to marmoset monkeys, no effect could be seen in cells bearing the CD2 (LFA-2) epitope."} {"id": "PMID:1282191", "title": "Structure and biosynthesis of unbranched multicopy single-stranded DNA by reverse transcriptase in a clinical Escherichia coli isolate.", "content": "It has been shown that retrons, retro-elements in bacteria, produce a reverse transcriptase (RT) and multicopy single-stranded DNA (msDNA) whose 5' end is covalently linked to RNA (msdRNA) by a 2'-5' phosphodiester bond. Here, I show that a retron in clinical Escherichia coli strain 161 produces an msDNA unlinked to RNA. The msDNA produced by this retron is a 79-nucleotide-long single-stranded DNA with monophosphate on its 5' terminus. When the retron in strain 161 is cloned into E. coli K-12, the majority of msDNA produced in the clone is the same as the msDNA in the clinical strain. However, in the K-12 clone, about 10% of the msDNA produced is present as a DNA covalently linked to RNA. The DNA part of this RNA-DNA compound is an 83 nucleotides long with the same sequence as the unbranched msDNA, except for the presence of four additional nucleotides at the 5' side. From the analysis of the RNA-DNA compound and the results of in vitro synthesis, I show that the primary product of reverse transcription in this retron is an 83-nucleotide-long DNA covalently linked to RNA. This RNA-DNA compound is further processed to the final product, the 79-nucleotide-long msDNA with a terminal 5' monophosphate, by an endonucleolytic cleavage between the fourth and fifth positions of the DNA component of the RNA-DNA compound. The minimum region required for the production of such msDNA free of RNA contains only genes known to be required for the synthesis of branched msDNA-RNA compound in other retrons (msd, msr and ret). This suggests that either the RT has an endonuclease activity or that the msDNA-RNA compound is autocatalytically processed.", "contents": "Structure and biosynthesis of unbranched multicopy single-stranded DNA by reverse transcriptase in a clinical Escherichia coli isolate. It has been shown that retrons, retro-elements in bacteria, produce a reverse transcriptase (RT) and multicopy single-stranded DNA (msDNA) whose 5' end is covalently linked to RNA (msdRNA) by a 2'-5' phosphodiester bond. Here, I show that a retron in clinical Escherichia coli strain 161 produces an msDNA unlinked to RNA. The msDNA produced by this retron is a 79-nucleotide-long single-stranded DNA with monophosphate on its 5' terminus. When the retron in strain 161 is cloned into E. coli K-12, the majority of msDNA produced in the clone is the same as the msDNA in the clinical strain. However, in the K-12 clone, about 10% of the msDNA produced is present as a DNA covalently linked to RNA. The DNA part of this RNA-DNA compound is an 83 nucleotides long with the same sequence as the unbranched msDNA, except for the presence of four additional nucleotides at the 5' side. From the analysis of the RNA-DNA compound and the results of in vitro synthesis, I show that the primary product of reverse transcription in this retron is an 83-nucleotide-long DNA covalently linked to RNA. This RNA-DNA compound is further processed to the final product, the 79-nucleotide-long msDNA with a terminal 5' monophosphate, by an endonucleolytic cleavage between the fourth and fifth positions of the DNA component of the RNA-DNA compound. The minimum region required for the production of such msDNA free of RNA contains only genes known to be required for the synthesis of branched msDNA-RNA compound in other retrons (msd, msr and ret). This suggests that either the RT has an endonuclease activity or that the msDNA-RNA compound is autocatalytically processed."} {"id": "PMID:1282192", "title": "Functional analysis of the gas vesicle gene cluster of the halophilic archaeon Haloferax mediterranei defines the vac-region boundary and suggests a regulatory role for the gvpD gene or its product.", "content": "A series of deletions introduced into the gvp gene cluster of Haloferax mediterranei, comprising 14 genes involved in gas vesicle synthesis (mc-vac-region), was investigated by transformation experiments. Gas vesicle production and the expression of the gvpA gene encoding the major gas vesicle protein, GvpA, was monitored in each Haloferax volcanii transformant. Whereas transformants containing the entire mc-vac-region produced gas vesicles (Vac+), various deletions in the region 5' to gvpA (encompassing gvpD-gvpM) or 3' to gvpA (containing gvpC, gvpN and gvpO) revealed Vac- transformants. All these transformants expressed gvpA and contained the 8 kDa GvpA protein as shown by Western analysis. However, transformants containing the gvpA gene by itself indicated a lower level of GvpA than observed with each of the other transformants. None of these transformants containing deletion constructs assembled the GvpA protein into gas vesicles. In contrast, transformants containing a construct carrying a 918 bp deletion internal to gvpD exhibited a tremendous gas vesicle overproduction, suggesting a regulatory role for the gvpD gene or its product. This is the first assignment of a functional role for one of the 13 halobacterial gvp genes found in addition to gvpA that are involved in the synthesis of this unique structure.", "contents": "Functional analysis of the gas vesicle gene cluster of the halophilic archaeon Haloferax mediterranei defines the vac-region boundary and suggests a regulatory role for the gvpD gene or its product. A series of deletions introduced into the gvp gene cluster of Haloferax mediterranei, comprising 14 genes involved in gas vesicle synthesis (mc-vac-region), was investigated by transformation experiments. Gas vesicle production and the expression of the gvpA gene encoding the major gas vesicle protein, GvpA, was monitored in each Haloferax volcanii transformant. Whereas transformants containing the entire mc-vac-region produced gas vesicles (Vac+), various deletions in the region 5' to gvpA (encompassing gvpD-gvpM) or 3' to gvpA (containing gvpC, gvpN and gvpO) revealed Vac- transformants. All these transformants expressed gvpA and contained the 8 kDa GvpA protein as shown by Western analysis. However, transformants containing the gvpA gene by itself indicated a lower level of GvpA than observed with each of the other transformants. None of these transformants containing deletion constructs assembled the GvpA protein into gas vesicles. In contrast, transformants containing a construct carrying a 918 bp deletion internal to gvpD exhibited a tremendous gas vesicle overproduction, suggesting a regulatory role for the gvpD gene or its product. This is the first assignment of a functional role for one of the 13 halobacterial gvp genes found in addition to gvpA that are involved in the synthesis of this unique structure."} {"id": "PMID:1282193", "title": "Regulation of the Escherichia coli uncH gene by mRNA secondary structure and translational coupling.", "content": "The uncH gene is one of the most poorly-expressed genes of the proton-translocating ATPase (unc) operon of Escherichia coli. We constructed in-frame lacZ fusions to uncH and used site-directed mutagenesis to decrease the stability of the putative mRNA secondary structure in the Shine and Dalgarno region for this gene. These mutations significantly increased the expression of uncH. We also used the unc-lac fusions to show that the insertion of stop codons and a frameshift mutation in uncF, the gene preceding uncH, caused a 10-fold reduction in uncH expression. Hybridization of total cellular RNA with a lacZ-specific probe indicated that transcriptional polarity could not account for the observed decrease in gene expression. These results demonstrate that uncH expression is controlled by mRNA sequences around the translational initiation region, and is translationally coupled to uncF, even in cases where the putative mRNA secondary structure is weakened or eliminated.", "contents": "Regulation of the Escherichia coli uncH gene by mRNA secondary structure and translational coupling. The uncH gene is one of the most poorly-expressed genes of the proton-translocating ATPase (unc) operon of Escherichia coli. We constructed in-frame lacZ fusions to uncH and used site-directed mutagenesis to decrease the stability of the putative mRNA secondary structure in the Shine and Dalgarno region for this gene. These mutations significantly increased the expression of uncH. We also used the unc-lac fusions to show that the insertion of stop codons and a frameshift mutation in uncF, the gene preceding uncH, caused a 10-fold reduction in uncH expression. Hybridization of total cellular RNA with a lacZ-specific probe indicated that transcriptional polarity could not account for the observed decrease in gene expression. These results demonstrate that uncH expression is controlled by mRNA sequences around the translational initiation region, and is translationally coupled to uncF, even in cases where the putative mRNA secondary structure is weakened or eliminated."} {"id": "PMID:1282194", "title": "The gene encoding the cellulase (Avicelase) Cel1 from Streptomyces reticuli and analysis of protein domains.", "content": "Streptomyces reticuli produces an unusual cellulase (Avicelase), with an apparent molecular weight of 82 kDa, which is solely sufficient to degrade crystalline cellulose. During cultivation the processing of the Avicelase to a truncated enzyme (42 kDa) and an inactive protein (40 kDa) correlated with the occurrence of an extracellular protease. After its purification this 36 kDa protease cleaved the S. reticuli Avicelase in vitro in the same manner. Using antibodies raised against the Avicelase and its truncated form (42 kDa) and gene libraries of S. reticuli DNA in the Escherichia coli phage vectors lambda gt11 and Charon 35, the Avicelase gene (cel1) was identified. Further subcloning and DNA-sequencing revealed a G+C rich (72%) reading frame of 2238 bp encoding a protein of 746 amino acids. The transcriptional start site was mapped about 180 bp upstream from the GTG start codon. A signal sequence of 29 amino acids was identified by aligning the deduced amino acids with the characterized N-terminus of the 82 kDa Avicelase. Comparison of the N-terminal amino acids from the purified proteins with the amino acid sequence derived from the Avicelase gene revealed that the truncated enzyme (42 kDa) corresponds to the C-terminal region whereas the inactive proteolytically derived protein (40 kDa) represents the N-terminal part of the 82 kDa Avicelase. Comparisons with amino acid sequences deduced from known cellulase genes indicated the presence of three putative protein domains: (i) an N-terminal part showing significant similarity with a repeat region of endoglucanase C from Cellulomonas fimi, recently shown to be a cellulose-binding domain; (ii) an adjoining region sharing homology with the N-terminal domains with unknown function of endoglucanase A from Pseudomonas fluorescens, endoglucanase D from Clostridium thermocellum and a cellodextrinase from Butyrivibrio fibrisolvens, and (iii) a C-terminal catalytic domain belonging to cellulase family E.", "contents": "The gene encoding the cellulase (Avicelase) Cel1 from Streptomyces reticuli and analysis of protein domains. Streptomyces reticuli produces an unusual cellulase (Avicelase), with an apparent molecular weight of 82 kDa, which is solely sufficient to degrade crystalline cellulose. During cultivation the processing of the Avicelase to a truncated enzyme (42 kDa) and an inactive protein (40 kDa) correlated with the occurrence of an extracellular protease. After its purification this 36 kDa protease cleaved the S. reticuli Avicelase in vitro in the same manner. Using antibodies raised against the Avicelase and its truncated form (42 kDa) and gene libraries of S. reticuli DNA in the Escherichia coli phage vectors lambda gt11 and Charon 35, the Avicelase gene (cel1) was identified. Further subcloning and DNA-sequencing revealed a G+C rich (72%) reading frame of 2238 bp encoding a protein of 746 amino acids. The transcriptional start site was mapped about 180 bp upstream from the GTG start codon. A signal sequence of 29 amino acids was identified by aligning the deduced amino acids with the characterized N-terminus of the 82 kDa Avicelase. Comparison of the N-terminal amino acids from the purified proteins with the amino acid sequence derived from the Avicelase gene revealed that the truncated enzyme (42 kDa) corresponds to the C-terminal region whereas the inactive proteolytically derived protein (40 kDa) represents the N-terminal part of the 82 kDa Avicelase. Comparisons with amino acid sequences deduced from known cellulase genes indicated the presence of three putative protein domains: (i) an N-terminal part showing significant similarity with a repeat region of endoglucanase C from Cellulomonas fimi, recently shown to be a cellulose-binding domain; (ii) an adjoining region sharing homology with the N-terminal domains with unknown function of endoglucanase A from Pseudomonas fluorescens, endoglucanase D from Clostridium thermocellum and a cellodextrinase from Butyrivibrio fibrisolvens, and (iii) a C-terminal catalytic domain belonging to cellulase family E."} {"id": "PMID:1282195", "title": "Differentiation of light-dye effects in the microcirculation.", "content": "Activation of photosensitive compounds has been used in the treatment of tumors and as a technique to study various microcirculatory phenomena. This technique may be accompanied by deleterious effects which may complicate interpretations of experimental results. However, the relevant physiological mechanisms that induce toxicity and the light doses needed to produce different toxic reactions have not been well defined. In the current study, the rat cremaster muscle preparation was used with in vivo fluorescent television microscopy and subsequently with electron and light microscopy to evaluate toxic reactions of light activation of fluorescein isothiocyanate. The most sensitive photoactive reactions were macromolecular leakage and platelet activation, occurring with 120 J/cm2 activation energy. Macromolecular leakage was at least partially restricted by perivenular and pericapillary pericytes and there was no morphological damage with this light dose. Since macromolecular leakage was significantly inhibited by pretreatment with diphenhydramine or Compound 48/80, it is in part due to the release of histamine from tissue mast cells. 720 J/cm2 reduced the red blood cell column in the venules by over 50% due to platelet thrombus formation, an effect that was accentuated by pretreatment with indomethacin. This suggests an inhibitory role of prostaglandins in platelet thrombus formation. In addition, 720 J/cm2 caused endothelial and smooth muscle cell swelling and ruptures, gap formation, and leukocyte and protein accumulation in the vessel walls.", "contents": "Differentiation of light-dye effects in the microcirculation. Activation of photosensitive compounds has been used in the treatment of tumors and as a technique to study various microcirculatory phenomena. This technique may be accompanied by deleterious effects which may complicate interpretations of experimental results. However, the relevant physiological mechanisms that induce toxicity and the light doses needed to produce different toxic reactions have not been well defined. In the current study, the rat cremaster muscle preparation was used with in vivo fluorescent television microscopy and subsequently with electron and light microscopy to evaluate toxic reactions of light activation of fluorescein isothiocyanate. The most sensitive photoactive reactions were macromolecular leakage and platelet activation, occurring with 120 J/cm2 activation energy. Macromolecular leakage was at least partially restricted by perivenular and pericapillary pericytes and there was no morphological damage with this light dose. Since macromolecular leakage was significantly inhibited by pretreatment with diphenhydramine or Compound 48/80, it is in part due to the release of histamine from tissue mast cells. 720 J/cm2 reduced the red blood cell column in the venules by over 50% due to platelet thrombus formation, an effect that was accentuated by pretreatment with indomethacin. This suggests an inhibitory role of prostaglandins in platelet thrombus formation. In addition, 720 J/cm2 caused endothelial and smooth muscle cell swelling and ruptures, gap formation, and leukocyte and protein accumulation in the vessel walls."} {"id": "PMID:1282196", "title": "Monoclonal antibodies against human alpha-fetoprotein more reactive to cell-surface alpha-fetoprotein than to free alpha-fetoprotein.", "content": "This paper describes the finding of monoclonal antibody (MoAb) more reactive to cell-surface alpha-fetoprotein (AFP) than to free AFP by using a simple in vitro system. Twelve mouse MoAbs, ten IgG1, one IgG2a and one IgG2b, against human AFP from hepatocellular carcinoma were obtained by the cell fusion technique. Each hybridoma supernatant was assayed by enzyme-linked immunosorbent assay (ELISA) to solid-phase AFP. The assay results showed that two MoAbs, 67D and 80G, were most reactive to AFP. 80G had a higher affinity constant than 67D, while the both reactions were similarly difficult to inhibit by free AFP in ELISA. 67D and 80G reacted with AFP on the surface of ethanol-fixed cells from the human hepatoma cell line HuH-7 and this reaction was also difficult to inhibit by free AFP in Cell ELISA. Furthermore, Western blot analysis showed that 67D and 80G were more reactive to membrane-bound AFP than other antibodies. These findings first suggest that there could be anti-AFP MoAbs preferably binding to cell-surface AFP rather than to serum AFP.", "contents": "Monoclonal antibodies against human alpha-fetoprotein more reactive to cell-surface alpha-fetoprotein than to free alpha-fetoprotein. This paper describes the finding of monoclonal antibody (MoAb) more reactive to cell-surface alpha-fetoprotein (AFP) than to free AFP by using a simple in vitro system. Twelve mouse MoAbs, ten IgG1, one IgG2a and one IgG2b, against human AFP from hepatocellular carcinoma were obtained by the cell fusion technique. Each hybridoma supernatant was assayed by enzyme-linked immunosorbent assay (ELISA) to solid-phase AFP. The assay results showed that two MoAbs, 67D and 80G, were most reactive to AFP. 80G had a higher affinity constant than 67D, while the both reactions were similarly difficult to inhibit by free AFP in ELISA. 67D and 80G reacted with AFP on the surface of ethanol-fixed cells from the human hepatoma cell line HuH-7 and this reaction was also difficult to inhibit by free AFP in Cell ELISA. Furthermore, Western blot analysis showed that 67D and 80G were more reactive to membrane-bound AFP than other antibodies. These findings first suggest that there could be anti-AFP MoAbs preferably binding to cell-surface AFP rather than to serum AFP."} {"id": "PMID:1282197", "title": "Effects of gamma-interferon and FK506 on resting B cell proliferation of New Zealand black/white F1 mice.", "content": "We examined the effects of gamma-interferon (gamma-IFN) and the new immunosuppressant FK506 on resting B cell proliferation of New Zealand black/white F1 hybrid (B/W F1) mice, an animal model of human systemic lupus erythematosus (SLE). gamma-IFN and FK506 inhibited in a dose-dependent manner both B cell proliferation and autoantibody production of resting B cells respectively. There was a synergistic interaction between gamma-IFN and FK506 in their inhibition and they did not exhibit cell cytotoxicity. This in vitro synergism of gamma-IFN and FK506 may have clinical application in that low doses of gamma-IFN and FK506 combinations may be effective to correct polyclonal B cell activation of patients with SLE.", "contents": "Effects of gamma-interferon and FK506 on resting B cell proliferation of New Zealand black/white F1 mice. We examined the effects of gamma-interferon (gamma-IFN) and the new immunosuppressant FK506 on resting B cell proliferation of New Zealand black/white F1 hybrid (B/W F1) mice, an animal model of human systemic lupus erythematosus (SLE). gamma-IFN and FK506 inhibited in a dose-dependent manner both B cell proliferation and autoantibody production of resting B cells respectively. There was a synergistic interaction between gamma-IFN and FK506 in their inhibition and they did not exhibit cell cytotoxicity. This in vitro synergism of gamma-IFN and FK506 may have clinical application in that low doses of gamma-IFN and FK506 combinations may be effective to correct polyclonal B cell activation of patients with SLE."} {"id": "PMID:1282198", "title": "The blood group antigen-related glycoepitopes: key structural determinants in immunogenesis and AIDS pathogenesis.", "content": "This overview will focus on the functional and pathophysiological aspects of blood group antigen (BGA)-related glycodeterminants with regard to immunogenesis and AIDS pathogenesis. It has been postulated that in a broad range of histogenetically different tissues and organs, BGA-related glycoepitopes are expressed on the cell surface at definite stages of cell differentiation. These glycoepitopes are expressed during embryogenesis, organogenesis, tissue repair, regeneration, remodelling and maturation when 'sorting-out' of one homotypic cell population from a heterotypic assemblage of cells occurs (1). In this event, the BGA-related glycoepitopes, if being expressed on the cell surface, play roles of key structural determinants in cell-cell recognition, association and aggregation. This mechanism will be discussed in relation to immunogenesis with regard to antigen presentation, self-non-self discrimination, and positive and negative selection during thymic education. It is postulated that the appearance of BGA-related glycoepitopes on the cell membrane is a consequence of the association of major histocompatibility complex antigens (MHC) and peptides, with the subsequent elimination of cells carrying a high density of BGA-related glycoepitopes on their surface. After human immunodeficiency virus (HIV) glycoproteins are glycosylated by host cell glycosyltransferases, the virus may use the BGA-related glycodeterminants as ligands and/or receptors for expansion to a spectrum of target cells during AIDS development and generalization of the infection throughout the body. We will review the experimental evidence that supports the concept that HIV uses an alternative to the gp120/CD4 ligand/receptor system, and that the alternative mechanism is probably carbohydrate-mediated in nature.", "contents": "The blood group antigen-related glycoepitopes: key structural determinants in immunogenesis and AIDS pathogenesis. This overview will focus on the functional and pathophysiological aspects of blood group antigen (BGA)-related glycodeterminants with regard to immunogenesis and AIDS pathogenesis. It has been postulated that in a broad range of histogenetically different tissues and organs, BGA-related glycoepitopes are expressed on the cell surface at definite stages of cell differentiation. These glycoepitopes are expressed during embryogenesis, organogenesis, tissue repair, regeneration, remodelling and maturation when 'sorting-out' of one homotypic cell population from a heterotypic assemblage of cells occurs (1). In this event, the BGA-related glycoepitopes, if being expressed on the cell surface, play roles of key structural determinants in cell-cell recognition, association and aggregation. This mechanism will be discussed in relation to immunogenesis with regard to antigen presentation, self-non-self discrimination, and positive and negative selection during thymic education. It is postulated that the appearance of BGA-related glycoepitopes on the cell membrane is a consequence of the association of major histocompatibility complex antigens (MHC) and peptides, with the subsequent elimination of cells carrying a high density of BGA-related glycoepitopes on their surface. After human immunodeficiency virus (HIV) glycoproteins are glycosylated by host cell glycosyltransferases, the virus may use the BGA-related glycodeterminants as ligands and/or receptors for expansion to a spectrum of target cells during AIDS development and generalization of the infection throughout the body. We will review the experimental evidence that supports the concept that HIV uses an alternative to the gp120/CD4 ligand/receptor system, and that the alternative mechanism is probably carbohydrate-mediated in nature."} {"id": "PMID:1282199", "title": "Derivation of a basic mechanism of control for embryonic genes as a specific subset.", "content": "The alpha-fetoprotein gene is conceived as being methylated in the zygote and according to the model is in a heterochromatic state and is therefore in a non-functional condition. Specific DNA methylase genes would produce methylases capable of alkylating enhancer regions of alpha-fetoprotein and certain proteins that would alter the heterochromatin condition. Also involved is a gene for the synthesis of a conformational-inducer protein that is proposed to be capable of blocking genic regions from reheterochromatizing. One of the pivotal events is the accumulation of S-adenosyl-L-methionine that reaches intracellular pool concentrations allowing other redundant active S-adenosyltransferase genes to become active. During embryogenesis specific conformational-inducer proteins would block genes such as the gene for albumin from reheterochromatizing while alpha-fetoprotein gene becomes heterochromatized during subsequent cell cycles. This heterochromatin is formed with embryonic type proteins sensitive to ribosylation-induced conformational changes. The increase in synthesis of alpha-fetoprotein followed by a decrease as albumin synthesis increases during embryogenesis is predicted by the scheme.", "contents": "Derivation of a basic mechanism of control for embryonic genes as a specific subset. The alpha-fetoprotein gene is conceived as being methylated in the zygote and according to the model is in a heterochromatic state and is therefore in a non-functional condition. Specific DNA methylase genes would produce methylases capable of alkylating enhancer regions of alpha-fetoprotein and certain proteins that would alter the heterochromatin condition. Also involved is a gene for the synthesis of a conformational-inducer protein that is proposed to be capable of blocking genic regions from reheterochromatizing. One of the pivotal events is the accumulation of S-adenosyl-L-methionine that reaches intracellular pool concentrations allowing other redundant active S-adenosyltransferase genes to become active. During embryogenesis specific conformational-inducer proteins would block genes such as the gene for albumin from reheterochromatizing while alpha-fetoprotein gene becomes heterochromatized during subsequent cell cycles. This heterochromatin is formed with embryonic type proteins sensitive to ribosylation-induced conformational changes. The increase in synthesis of alpha-fetoprotein followed by a decrease as albumin synthesis increases during embryogenesis is predicted by the scheme."} {"id": "PMID:1282200", "title": "Human placental mast cells: a role in pre-eclampsia?", "content": "The human placenta contains a significant amount of histamine, a potent vasoconstrictor of the placental vasculature, shown by the author to be stored within the tissues' mast cells. The proposed hypothesis suggests that placental mast cells may have an important role in normal and, or pathological processes during pregnancy. This suggestion will be applied to the confounding problem of pre-eclampsia, a complication of pregnancy characterised by hypertension, oedema and proteinuria, which is associated with increased morbidity and mortality of mother and baby. It is postulated that pre-eclampsia reflects an inflammatory-type reaction, in which mast cell-mediated events play a significant role. The mediators released upon mast cell activation, such as histamine and prostaglandins, may be involved in the vasospasm that characterises pre-eclampsia; while processes such as uptake and clearance of vasoactive mediators by mast cells may be important in normotensive pregnancies and upset in those women who develop pre-eclampsia.", "contents": "Human placental mast cells: a role in pre-eclampsia? The human placenta contains a significant amount of histamine, a potent vasoconstrictor of the placental vasculature, shown by the author to be stored within the tissues' mast cells. The proposed hypothesis suggests that placental mast cells may have an important role in normal and, or pathological processes during pregnancy. This suggestion will be applied to the confounding problem of pre-eclampsia, a complication of pregnancy characterised by hypertension, oedema and proteinuria, which is associated with increased morbidity and mortality of mother and baby. It is postulated that pre-eclampsia reflects an inflammatory-type reaction, in which mast cell-mediated events play a significant role. The mediators released upon mast cell activation, such as histamine and prostaglandins, may be involved in the vasospasm that characterises pre-eclampsia; while processes such as uptake and clearance of vasoactive mediators by mast cells may be important in normotensive pregnancies and upset in those women who develop pre-eclampsia."} {"id": "PMID:1282202", "title": "Cytokine-mediated regulation of monocyte/macrophage cytotoxicity in human immunodeficiency virus-1 infection.", "content": "Monocyte/macrophage-mediated tumor cytotoxicity was studied in patients infected with human immunodeficiency virus-1 (HIV-1) at various stages [Center for disease control (CDC) classification] of the disease. using the P-815 tumor cell line as target cells, the results demonstrated reduced monocyte/macrophage cytotoxicity early in HIV-1-related disease (CDCIII, P < 0.01). This cellular dysfunction sustained during the progression of the disease. Evidence could be presented that neither exogenous application of macrophage-stimulating cytokines (e.g. interferons) nor their endogenous induction in vitro restored monocyte/macrophage cytotoxicity. However, enhanced tumor necrosis factor (TNF)-alpha production, which parallels the observed reduced capacity to lyse P-815 tumor cells, might be the major source for monocyte/macrophage-mediated cell lysis. TNF-alpha-induced cytotoxicity can be inhibited by addition of anti-TNF-alpha. Other experimental models using TNF-sensitive tumor target cells may, therefore, mimic monocyte/macrophage-mediated lysis. Suppression of monocyte/macrophage cytotoxicity in later stages of HIV-1 infection (AIDS-related complex, AIDS) could partly be reverted by treatment with the cyclooxygenase blocker, indomethacin. The responsible arachidonic acid product mediating suppression was found to be prostaglandin E2, suggesting that in addition to the direct viral interference cellular dysfunction is at least in part a result of altered cytokine regulation.", "contents": "Cytokine-mediated regulation of monocyte/macrophage cytotoxicity in human immunodeficiency virus-1 infection. Monocyte/macrophage-mediated tumor cytotoxicity was studied in patients infected with human immunodeficiency virus-1 (HIV-1) at various stages [Center for disease control (CDC) classification] of the disease. using the P-815 tumor cell line as target cells, the results demonstrated reduced monocyte/macrophage cytotoxicity early in HIV-1-related disease (CDCIII, P < 0.01). This cellular dysfunction sustained during the progression of the disease. Evidence could be presented that neither exogenous application of macrophage-stimulating cytokines (e.g. interferons) nor their endogenous induction in vitro restored monocyte/macrophage cytotoxicity. However, enhanced tumor necrosis factor (TNF)-alpha production, which parallels the observed reduced capacity to lyse P-815 tumor cells, might be the major source for monocyte/macrophage-mediated cell lysis. TNF-alpha-induced cytotoxicity can be inhibited by addition of anti-TNF-alpha. Other experimental models using TNF-sensitive tumor target cells may, therefore, mimic monocyte/macrophage-mediated lysis. Suppression of monocyte/macrophage cytotoxicity in later stages of HIV-1 infection (AIDS-related complex, AIDS) could partly be reverted by treatment with the cyclooxygenase blocker, indomethacin. The responsible arachidonic acid product mediating suppression was found to be prostaglandin E2, suggesting that in addition to the direct viral interference cellular dysfunction is at least in part a result of altered cytokine regulation."} {"id": "PMID:1282203", "title": "Mutation analysis of genetic diseases by asymmetric-PCR SSCP and ethidium bromide staining: application to neurofibromatosis and cystic fibrosis.", "content": "The Single Strand Conformation Polymorphism (SSCP) technique is widely used in mutation analysis. We have introduced several modifications to the SSCP method, which overcome the problem of incomplete denaturation or reannealing of DNA during electrophoresis. The modifications consist of asymmetrical PCR amplification of the sequence of interest, electrophoresis with a higher concentration of acrylamide, and the analysis of the DNA fragments under u.v. light. We have applied this method to the analysis of two specific diseases: neurofibromatosis type 1 (NF1) and cystic fibrosis (CF) from PCR amplified exons. Two single nucleotide changes were observed with this method.", "contents": "Mutation analysis of genetic diseases by asymmetric-PCR SSCP and ethidium bromide staining: application to neurofibromatosis and cystic fibrosis. The Single Strand Conformation Polymorphism (SSCP) technique is widely used in mutation analysis. We have introduced several modifications to the SSCP method, which overcome the problem of incomplete denaturation or reannealing of DNA during electrophoresis. The modifications consist of asymmetrical PCR amplification of the sequence of interest, electrophoresis with a higher concentration of acrylamide, and the analysis of the DNA fragments under u.v. light. We have applied this method to the analysis of two specific diseases: neurofibromatosis type 1 (NF1) and cystic fibrosis (CF) from PCR amplified exons. Two single nucleotide changes were observed with this method."} {"id": "PMID:1282204", "title": "Tandem competitive polymerase chain reaction (TC-PCR): a method for determining ratios of RNA and DNA templates.", "content": "A sensitive and accurate method for determining the ratios of RNA and DNA templates by polymerase chain reaction (PCR) is presented. A common competitor containing tandemly arranged internal standards differing from the target template by the presence of different restriction enzyme sites is coamplified with the target templates under identical conditions. Products from each template and internal standard are identified by the band pattern after digestion with the restriction enzyme. As the amount of the common competitor is kept constant for all target templates, the ratio of PCR products from the templates reflects their ratio in the reaction mix before amplification. The method was used to study the relative abundance of mRNA for the pro-alpha1 and pro-alpha2 chains of type I collagen and for estimating disturbances of normal ratio in the inherited bone disorder, osteogenesis imperfecta.", "contents": "Tandem competitive polymerase chain reaction (TC-PCR): a method for determining ratios of RNA and DNA templates. A sensitive and accurate method for determining the ratios of RNA and DNA templates by polymerase chain reaction (PCR) is presented. A common competitor containing tandemly arranged internal standards differing from the target template by the presence of different restriction enzyme sites is coamplified with the target templates under identical conditions. Products from each template and internal standard are identified by the band pattern after digestion with the restriction enzyme. As the amount of the common competitor is kept constant for all target templates, the ratio of PCR products from the templates reflects their ratio in the reaction mix before amplification. The method was used to study the relative abundance of mRNA for the pro-alpha1 and pro-alpha2 chains of type I collagen and for estimating disturbances of normal ratio in the inherited bone disorder, osteogenesis imperfecta."} {"id": "PMID:1282205", "title": "A comparison of procedures for analysing microsatellite (CA)-repeat polymorphisms.", "content": "Dinucleotide repeat sequences ('microsatellites') have been used as polymorphic genetic markers following amplification in the polymerase chain reaction (PCR). We have compared several methods of analysing the PCR products. The most reliable and unambiguous results were obtained when the PCR products were probed with a specific dinucleotide repeat oligonucleotide, so that only the microsatellite-containing products were detectable.", "contents": "A comparison of procedures for analysing microsatellite (CA)-repeat polymorphisms. Dinucleotide repeat sequences ('microsatellites') have been used as polymorphic genetic markers following amplification in the polymerase chain reaction (PCR). We have compared several methods of analysing the PCR products. The most reliable and unambiguous results were obtained when the PCR products were probed with a specific dinucleotide repeat oligonucleotide, so that only the microsatellite-containing products were detectable."} {"id": "PMID:1282206", "title": "Genotoxicity of heated cooking oil vapors.", "content": "Epidemiological studies of lung cancer in Chinese women indicated that factors other than cigarette smoking are related to lung cancer risk. A case-control study suggested that indoor air pollution, particularly from cooking oil emissions, may be involved. Condensates of volatile emissions from rapeseed and soybean cooking oils were prepared and found to be genotoxic in short-term tests including the Salmonella mutation assay, SV50 forward-mutation assay, and sister-chromatid exchange assay, as well as the micronucleus assay in mouse bone marrow. In contrast, condensates from rapeseed oil with butylated hydroxyanisole or hydrogenated rapeseed oil were not mutagenic, implicating oxidation products as the cause for mutagenicity. Peanut oil and lard condensates were not mutagenic in any assay. The association of exposure to Chinese rapeseed cooking-oil emissions and lung-cancer risk may be related to the mutagenic component of these condensates.", "contents": "Genotoxicity of heated cooking oil vapors. Epidemiological studies of lung cancer in Chinese women indicated that factors other than cigarette smoking are related to lung cancer risk. A case-control study suggested that indoor air pollution, particularly from cooking oil emissions, may be involved. Condensates of volatile emissions from rapeseed and soybean cooking oils were prepared and found to be genotoxic in short-term tests including the Salmonella mutation assay, SV50 forward-mutation assay, and sister-chromatid exchange assay, as well as the micronucleus assay in mouse bone marrow. In contrast, condensates from rapeseed oil with butylated hydroxyanisole or hydrogenated rapeseed oil were not mutagenic, implicating oxidation products as the cause for mutagenicity. Peanut oil and lard condensates were not mutagenic in any assay. The association of exposure to Chinese rapeseed cooking-oil emissions and lung-cancer risk may be related to the mutagenic component of these condensates."} {"id": "PMID:1282207", "title": "Urban air pollution: use of different mutagenicity assays to evaluate environmental genetic hazard.", "content": "The genotoxic activities associated with airborne particulate matter collected in Parma (northern Italy) have been determined. The airborne particle extracts were tested for mutagenicity using Salmonella frameshift (TA98) and base-substitution (TA100) tester strains with and without S9 microsomal activation and Saccharomyces cerevisiae strain D7 in order to determine the frequency of mitotic gene conversion and ilv1-92 mutant reversion in cells harvested at stationary and logarithmic growth phase. The relationship between mitochondrial DNA mutations and ageing, degenerative diseases and cancer prompted us to take into account the mitochondrial informational target, i.e., the respiratory-deficient (RD) mutants. The results obtained show a variability in the response for the different test systems during different months. The Salmonella mutagenicity trend was directly correlated with carbon monoxide, nitrogen oxides (NOx) and Pb concentration in airborne particulates and inversely correlated with temperature, whereas the mitochondrial genotoxic effect was higher during spring and late summer. These data suggest that the genotoxic risk assessment is a time-dependent value strictly correlated with the evaluation system being tested.", "contents": "Urban air pollution: use of different mutagenicity assays to evaluate environmental genetic hazard. The genotoxic activities associated with airborne particulate matter collected in Parma (northern Italy) have been determined. The airborne particle extracts were tested for mutagenicity using Salmonella frameshift (TA98) and base-substitution (TA100) tester strains with and without S9 microsomal activation and Saccharomyces cerevisiae strain D7 in order to determine the frequency of mitotic gene conversion and ilv1-92 mutant reversion in cells harvested at stationary and logarithmic growth phase. The relationship between mitochondrial DNA mutations and ageing, degenerative diseases and cancer prompted us to take into account the mitochondrial informational target, i.e., the respiratory-deficient (RD) mutants. The results obtained show a variability in the response for the different test systems during different months. The Salmonella mutagenicity trend was directly correlated with carbon monoxide, nitrogen oxides (NOx) and Pb concentration in airborne particulates and inversely correlated with temperature, whereas the mitochondrial genotoxic effect was higher during spring and late summer. These data suggest that the genotoxic risk assessment is a time-dependent value strictly correlated with the evaluation system being tested."} {"id": "PMID:1282208", "title": "Mutagenic activity of the leachate of municipal solid waste landfill.", "content": "Organic concentrates were recovered using XAD-2/8 resin adsorption from the leachates of municipal solid waste landfills and their mutagenic activities were tested for 8 months using the Ames Salmonella/microsome assay. Highly polluted leachates (COD and BOD > or = 40 mg/l) generally had equal or higher mutagenic activities than lightly polluted leachates (COD and BOD < 40 mg/l). But there was no clear difference in mutagenicity per amount of concentrate between the two leachates. These results suggest that the mutagenic activity of landfill leachate is decided to some degree by the organic concentration in the leachate. The mutagenic activities detected even in lightly polluted leachates were not so low as those of various kind of surface waters ever reported. It is suggested that it is important to investigate the mutagenic activity of the leachate for evaluation of the impact of landfill leachate on the environment.", "contents": "Mutagenic activity of the leachate of municipal solid waste landfill. Organic concentrates were recovered using XAD-2/8 resin adsorption from the leachates of municipal solid waste landfills and their mutagenic activities were tested for 8 months using the Ames Salmonella/microsome assay. Highly polluted leachates (COD and BOD > or = 40 mg/l) generally had equal or higher mutagenic activities than lightly polluted leachates (COD and BOD < 40 mg/l). But there was no clear difference in mutagenicity per amount of concentrate between the two leachates. These results suggest that the mutagenic activity of landfill leachate is decided to some degree by the organic concentration in the leachate. The mutagenic activities detected even in lightly polluted leachates were not so low as those of various kind of surface waters ever reported. It is suggested that it is important to investigate the mutagenic activity of the leachate for evaluation of the impact of landfill leachate on the environment."} {"id": "PMID:1282209", "title": "Cytogenetic effects of diazepam in peripheral lymphocytes of self-poisoned persons.", "content": "The frequencies of chromosomal aberrations and of micronuclei were determined in lymphocyte cultures of 25 patients who attempted suicide with diazepam, 6-12 h, 72 h and 30 days after self-poisoning. These data were compared with those of healthy controls. The frequencies of numerical aberrations showed a significant increase immediately after self-poisoning. However, this effect could not be detected on the 3rd and 30th days after self-poisoning.", "contents": "Cytogenetic effects of diazepam in peripheral lymphocytes of self-poisoned persons. The frequencies of chromosomal aberrations and of micronuclei were determined in lymphocyte cultures of 25 patients who attempted suicide with diazepam, 6-12 h, 72 h and 30 days after self-poisoning. These data were compared with those of healthy controls. The frequencies of numerical aberrations showed a significant increase immediately after self-poisoning. However, this effect could not be detected on the 3rd and 30th days after self-poisoning."} {"id": "PMID:1282213", "title": "Cytogenetic damage induced in human lymphocytes by sodium bisulfite.", "content": "The frequencies of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), and micronuclei (MN) in human blood lymphocytes exposed to sodium bisulfite (sulfur dioxide) at various concentrations ranging from 5 x 10(-5) M to 2 x 10(-3) M in vitro were studied. It was shown that sodium bisulfite (NaHSO3 and Na2SO3, 1:3 M/M) caused an increase in SCE and MN in human blood lymphocytes in a dose-dependent manner, and also induced mitotic delays and decreased mitotic index. For CA, our results indicated that sodium bisulfite induced an increase of chromatid-type aberrations in lymphocytes from three of four donors in a dose-dependent manner. The chemical at low concentrations induced chromatid-type aberrations, but not chromosome-type aberrations; high concentrations induced both chromatid- and chromosome-type aberrations. No cytogenetic damage in human lymphocytes was induced by sodium sulfate. The results have confirmed that sulfur dioxide is a clastogenic and genotoxic agent.", "contents": "Cytogenetic damage induced in human lymphocytes by sodium bisulfite. The frequencies of chromosomal aberrations (CA), sister-chromatid exchanges (SCE), and micronuclei (MN) in human blood lymphocytes exposed to sodium bisulfite (sulfur dioxide) at various concentrations ranging from 5 x 10(-5) M to 2 x 10(-3) M in vitro were studied. It was shown that sodium bisulfite (NaHSO3 and Na2SO3, 1:3 M/M) caused an increase in SCE and MN in human blood lymphocytes in a dose-dependent manner, and also induced mitotic delays and decreased mitotic index. For CA, our results indicated that sodium bisulfite induced an increase of chromatid-type aberrations in lymphocytes from three of four donors in a dose-dependent manner. The chemical at low concentrations induced chromatid-type aberrations, but not chromosome-type aberrations; high concentrations induced both chromatid- and chromosome-type aberrations. No cytogenetic damage in human lymphocytes was induced by sodium sulfate. The results have confirmed that sulfur dioxide is a clastogenic and genotoxic agent."} {"id": "PMID:1282214", "title": "Mutagenicity testing of imidazole and related compounds.", "content": "Ames tests have been performed with imidazole and its principal metabolites, hydantoin and hydantoic acid. N-Acetyl-imidazole, a potential metabolite resulting from the action of intestinal bacteria, and histamine, a structurally related compound which is widely distributed in mammalian tissues, have also been tested. Imidazole and histamine were also tested in the UDS assay in primary rat hepatocytes, while imidazole alone was tested in the M2-C3H mouse fibroblast malignant transformation assay. Imidazole gave consistently negative results in the Ames test, the UDS assay and the transformation assay. The three metabolites of imidazole, namely hydantoin, hydantoic acid and N-acetyl-imidazole, all gave negative results in the Ames test. Histamine gave no evidence of mutagenic activity in the Ames test or of genotoxicity in the UDS assay. These results indicate that imidazole and its metabolites are unlikely to present a mutagenic or carcinogenic hazard.", "contents": "Mutagenicity testing of imidazole and related compounds. Ames tests have been performed with imidazole and its principal metabolites, hydantoin and hydantoic acid. N-Acetyl-imidazole, a potential metabolite resulting from the action of intestinal bacteria, and histamine, a structurally related compound which is widely distributed in mammalian tissues, have also been tested. Imidazole and histamine were also tested in the UDS assay in primary rat hepatocytes, while imidazole alone was tested in the M2-C3H mouse fibroblast malignant transformation assay. Imidazole gave consistently negative results in the Ames test, the UDS assay and the transformation assay. The three metabolites of imidazole, namely hydantoin, hydantoic acid and N-acetyl-imidazole, all gave negative results in the Ames test. Histamine gave no evidence of mutagenic activity in the Ames test or of genotoxicity in the UDS assay. These results indicate that imidazole and its metabolites are unlikely to present a mutagenic or carcinogenic hazard."} {"id": "PMID:1282215", "title": "Acute cytogenetic effect of benzene on rat bone marrow cells in vivo and the effect of inducers or inhibitors of drug-metabolizing enzymes.", "content": "Acute cytogenetic effects of benzene in LE rat bone marrow cells in vivo were studied. Chromosome aberrations (CA) induced by benzene consisted mainly of gaps and breaks. Cells with exchanges were rarely observed. The incidence of benzene-induced CA was at its maximum level 12 h after the p.o. or i.p. administration of benzene, dependent on the dose of benzene administered, and higher in male rats than in female rats. However, the sex difference was not observed in the repeated inhalation experiment. Chromosome damage was higher with the p.o. than the i.p. administration. LE rats were more sensitive than Wistar and SD rats to the clastogenic action of benzene. Phenobarbital and Sudan III are well known as inducers of drug-metabolizing enzymes. The peak percentage of benzene-induced CA in the rats pretreated with phenobarbital was observed 6 h after the benzene injection, and it occurred at a higher level than in the rats given only benzene. On the other hand, Sudan III pretreatment suppressed benzene-induced CA at all periods after the benzene injection. SKF-525A (a cytochrome P-450 inhibitor) and cyclohexene oxide (an epoxide hydrase inhibitor) pretreatment also suppressed benzene-induced CA.", "contents": "Acute cytogenetic effect of benzene on rat bone marrow cells in vivo and the effect of inducers or inhibitors of drug-metabolizing enzymes. Acute cytogenetic effects of benzene in LE rat bone marrow cells in vivo were studied. Chromosome aberrations (CA) induced by benzene consisted mainly of gaps and breaks. Cells with exchanges were rarely observed. The incidence of benzene-induced CA was at its maximum level 12 h after the p.o. or i.p. administration of benzene, dependent on the dose of benzene administered, and higher in male rats than in female rats. However, the sex difference was not observed in the repeated inhalation experiment. Chromosome damage was higher with the p.o. than the i.p. administration. LE rats were more sensitive than Wistar and SD rats to the clastogenic action of benzene. Phenobarbital and Sudan III are well known as inducers of drug-metabolizing enzymes. The peak percentage of benzene-induced CA in the rats pretreated with phenobarbital was observed 6 h after the benzene injection, and it occurred at a higher level than in the rats given only benzene. On the other hand, Sudan III pretreatment suppressed benzene-induced CA at all periods after the benzene injection. SKF-525A (a cytochrome P-450 inhibitor) and cyclohexene oxide (an epoxide hydrase inhibitor) pretreatment also suppressed benzene-induced CA."} {"id": "PMID:1282216", "title": "Mutagenic activity in wastewater concentrates from dye plants.", "content": "Wastewater concentrates from the wastewater treatment systems of three dye plants were tested for mutagenic activity in Salmonella typhimurium TA98 and Escherichia coli WP2uvrA using a fluctuation assay. Concentrates were prepared by passing samples of wastewater (5-6 or 30 litres) through two porous resins (XAD-2 and XAD-7) in series. S. typhimurium in the presence of microsomal activation proved to be the more sensitive marker of mutagenicity. Mutagenic responses were observed in concentrates from all three plants tested. The results show that mutagenic activity was particularly high in the incoming waters and increased after active, biological treatment. Physico-chemical treatment may be effective in decreasing mutagenic activity, but only if appropriately used.", "contents": "Mutagenic activity in wastewater concentrates from dye plants. Wastewater concentrates from the wastewater treatment systems of three dye plants were tested for mutagenic activity in Salmonella typhimurium TA98 and Escherichia coli WP2uvrA using a fluctuation assay. Concentrates were prepared by passing samples of wastewater (5-6 or 30 litres) through two porous resins (XAD-2 and XAD-7) in series. S. typhimurium in the presence of microsomal activation proved to be the more sensitive marker of mutagenicity. Mutagenic responses were observed in concentrates from all three plants tested. The results show that mutagenic activity was particularly high in the incoming waters and increased after active, biological treatment. Physico-chemical treatment may be effective in decreasing mutagenic activity, but only if appropriately used."} {"id": "PMID:1282217", "title": "Mutagenesis and comutagenesis by lead compounds.", "content": "We have previously reported that lead(II) is weakly mutagenic to Chinese hamster V79 cells. A transgenic cell line G12 containing a single copy of the E. coli gpt gene was developed in this laboratory from Chinese hamster V79 cells. The gpt locus in the G12 cells is more mutable by radiation and oxidative agents compared with the endogenous hprt locus of wild-type V79 cells. We have investigated the mutagenicity of two lead compounds at the gpt locus in G12 cells. Only at a toxic dose is lead acetate significantly mutagenic to G12 cells. Lead nitrate is not significantly mutagenic at any dose. Although both compounds are water-soluble, lead acetate, but not lead nitrate, forms a fine white insoluble precipitate upon addition to growth medium. A nick translation assay on cells treated with lead compounds and then permeabilized indicated that lead nitrate and, to a greater extent, lead acetate causes the appearance of nicks in chromosomal DNA. Lead ions in the presence of hydrogen peroxide, but not alone, introduced nicks into supercoiled plasmid DNA in vitro, suggesting that lead ions can partake in a Fenton reaction and thereby damage DNA. At lower nonmutagenic concentrations, lead acetate enhances the mutagenicity of MNNG and ultraviolet light. DNA damage by ultraviolet light is not enhanced by lead ions in vitro. Our data support the concept that non-toxic concentrations of lead(II) can inhibit DNA repair. Thus, at biologically relevant doses, lead(II) could act as a comutagen and possibly a cocarcinogen, but is not likely to act as an initiating genotoxic carcinogen.", "contents": "Mutagenesis and comutagenesis by lead compounds. We have previously reported that lead(II) is weakly mutagenic to Chinese hamster V79 cells. A transgenic cell line G12 containing a single copy of the E. coli gpt gene was developed in this laboratory from Chinese hamster V79 cells. The gpt locus in the G12 cells is more mutable by radiation and oxidative agents compared with the endogenous hprt locus of wild-type V79 cells. We have investigated the mutagenicity of two lead compounds at the gpt locus in G12 cells. Only at a toxic dose is lead acetate significantly mutagenic to G12 cells. Lead nitrate is not significantly mutagenic at any dose. Although both compounds are water-soluble, lead acetate, but not lead nitrate, forms a fine white insoluble precipitate upon addition to growth medium. A nick translation assay on cells treated with lead compounds and then permeabilized indicated that lead nitrate and, to a greater extent, lead acetate causes the appearance of nicks in chromosomal DNA. Lead ions in the presence of hydrogen peroxide, but not alone, introduced nicks into supercoiled plasmid DNA in vitro, suggesting that lead ions can partake in a Fenton reaction and thereby damage DNA. At lower nonmutagenic concentrations, lead acetate enhances the mutagenicity of MNNG and ultraviolet light. DNA damage by ultraviolet light is not enhanced by lead ions in vitro. Our data support the concept that non-toxic concentrations of lead(II) can inhibit DNA repair. Thus, at biologically relevant doses, lead(II) could act as a comutagen and possibly a cocarcinogen, but is not likely to act as an initiating genotoxic carcinogen."} {"id": "PMID:1282218", "title": "Stimulation of ACTH/cortisol by intravenously infused substance P in normal men: inhibition by sodium valproate.", "content": "The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1 or 1.5 pmol/kg-1/min-1 over 60 min on ACTH/cortisol secretion was evaluated in 7 healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma ACTH and cortisol levels were not modified when normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when higher amounts of SP were administered. Further studies were performed in another 7 healthy men to test the possible influence of GABAergic neurotransmission on the ACTH/cortisol response to SP. For this purpose, subjects were tested with SP (1.5 pmol/kg-1/min-1) alone and on a different occasion with SP after pretreatment with the GABAergic agent sodium valproate (200 mg 16, 8 and 1 h before the SP test). Again, the administration of SP induced a significant increase in plasma ACTH and cortisol levels. The pretreatment with sodium valproate completely abolished both ACTH and cortisol responses to SP. These data demonstrate for the first time in humans that the systemic infusion of SP stimulates ACTH/cortisol secretion, suggesting the involvement of a GABAergic mechanism in the regulation of the action of SP.", "contents": "Stimulation of ACTH/cortisol by intravenously infused substance P in normal men: inhibition by sodium valproate. The effect of synthetic substance P (SP), infused intravenously in doses of 0.5, 1 or 1.5 pmol/kg-1/min-1 over 60 min on ACTH/cortisol secretion was evaluated in 7 healthy men. SP tests and a control test with normal saline were randomly performed at weekly intervals. During tests, SP infusion did not produce untoward side effects or changes in blood pressure. Plasma ACTH and cortisol levels were not modified when normal saline or the lowest dose of SP were infused, whereas they were significantly increased in a dose-dependent fashion when higher amounts of SP were administered. Further studies were performed in another 7 healthy men to test the possible influence of GABAergic neurotransmission on the ACTH/cortisol response to SP. For this purpose, subjects were tested with SP (1.5 pmol/kg-1/min-1) alone and on a different occasion with SP after pretreatment with the GABAergic agent sodium valproate (200 mg 16, 8 and 1 h before the SP test). Again, the administration of SP induced a significant increase in plasma ACTH and cortisol levels. The pretreatment with sodium valproate completely abolished both ACTH and cortisol responses to SP. These data demonstrate for the first time in humans that the systemic infusion of SP stimulates ACTH/cortisol secretion, suggesting the involvement of a GABAergic mechanism in the regulation of the action of SP."} {"id": "PMID:1282219", "title": "Diurnal variation in 5-hydroxyindole-acetic acid output in the suprachiasmatic region of the Siberian hamster assessed by in vivo microdialysis: evidence for nocturnal activation of serotonin release.", "content": "In vivo brain microdialysis was used to characterize the daily pattern of 5-hydroxyindole-acetic acid (5-HIAA) release in the region of the suprachiasmatic nuclei (SCN) in freely behaving male Siberian hamsters housed under 16L:8D. A marked diurnal variation in the concentration of extracellular 5-HIAA was apparent, with peak levels (147 +/- 5% of the daily mean; p < 0.05) occurring 2-3 h after lights-off. Smaller nocturnal rises in extracellular 5-HIAA were observed in the posterior hypothalamus and preoptic area (128 +/- 4 and 123 +/- 8% of the daily mean, respectively; both p < 0.05 vs. average daytime levels). Tryptophan loading increased 5-HIAA in SCN microdialysates by 44 +/- 6%, and this response was enhanced by localized perfusion with tetrodotoxin (TTX; 5 microM). Localized applications of KCl (150 mM) or veratridine (100 microM) decreased 5-HIAA by 62 +/- 5 or 49 +/- 11%, respectively. The effect of KCl was not significantly affected by specific calcium channel blockers. Perfusion with TTX markedly decreased SCN 5-HIAA during the dark phase, but had little effect during the light phase (42 +/- 8 vs. 12 +/- 5% suppression, respectively; p < 0.01). Addition of serotonin (3 microM) to the perfusate significantly stimulated 5-HIAA output. This treatment increased the release of 5-HIAA more during the dark than during the light phase (61 +/- 8 vs. 25 +/- 5%, respectively; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Diurnal variation in 5-hydroxyindole-acetic acid output in the suprachiasmatic region of the Siberian hamster assessed by in vivo microdialysis: evidence for nocturnal activation of serotonin release. In vivo brain microdialysis was used to characterize the daily pattern of 5-hydroxyindole-acetic acid (5-HIAA) release in the region of the suprachiasmatic nuclei (SCN) in freely behaving male Siberian hamsters housed under 16L:8D. A marked diurnal variation in the concentration of extracellular 5-HIAA was apparent, with peak levels (147 +/- 5% of the daily mean; p < 0.05) occurring 2-3 h after lights-off. Smaller nocturnal rises in extracellular 5-HIAA were observed in the posterior hypothalamus and preoptic area (128 +/- 4 and 123 +/- 8% of the daily mean, respectively; both p < 0.05 vs. average daytime levels). Tryptophan loading increased 5-HIAA in SCN microdialysates by 44 +/- 6%, and this response was enhanced by localized perfusion with tetrodotoxin (TTX; 5 microM). Localized applications of KCl (150 mM) or veratridine (100 microM) decreased 5-HIAA by 62 +/- 5 or 49 +/- 11%, respectively. The effect of KCl was not significantly affected by specific calcium channel blockers. Perfusion with TTX markedly decreased SCN 5-HIAA during the dark phase, but had little effect during the light phase (42 +/- 8 vs. 12 +/- 5% suppression, respectively; p < 0.01). Addition of serotonin (3 microM) to the perfusate significantly stimulated 5-HIAA output. This treatment increased the release of 5-HIAA more during the dark than during the light phase (61 +/- 8 vs. 25 +/- 5%, respectively; p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282220", "title": "Protein kinase C modulates the release of [3H]5-hydroxytryptamine in the spinal cord of the rat: the role of L-type voltage-dependent calcium channels.", "content": "The present studies examined the relationship between protein kinase C (PKC) and L-type voltage-dependent calcium channels in modulating the release of neurotransmitter from K(+)-depolarized rat spinal cord synaptosomes. Activators of PKC, such as phorbol 12-myristate 13-acetate (PMA), mezerein and oleoyl acetylglycerol produced a concentration-dependent potentiation of K(+)-induced release of [3H]5-hydroxytryptamine ([3H]5-HT). Enhanced release was dependent on the concentration of both Ca2+ and K+ in the superfusion medium. Calcium-independent release of [3H]5-HT or release induced by the Ca2+ ionophore were unaffected by PKC activators. Calcium-dependent release of [3H]5-HT, evoked by K+, was enhanced under similar conditions by the L-type Ca2+ channel agonists Bay K 8644 and (+)-SDZ 202-791. Nimodipine, an L-type Ca2+ channel antagonist, while having no independent effect on K(+)-induced release of [3H]5-HT, abolished the potentiative effects of Bay K 8644 and PMA. Similarly, the PKC inhibitors, polymyxin B and staurosporine, blocked effects of both PMA and Bay K 8644 on K(+)-stimulated release of [3H]5-HT. Neither PMA nor Bay K 8644 altered the uptake of [3H]5-HT. These results suggest that PKC-dependent mechanisms utilize calcium influx, via the L-type calcium channel, to modulate release of neurotransmitter and indicate a possible functional link between PKC and L-type voltage-dependent calcium channels in the spinal cord.", "contents": "Protein kinase C modulates the release of [3H]5-hydroxytryptamine in the spinal cord of the rat: the role of L-type voltage-dependent calcium channels. The present studies examined the relationship between protein kinase C (PKC) and L-type voltage-dependent calcium channels in modulating the release of neurotransmitter from K(+)-depolarized rat spinal cord synaptosomes. Activators of PKC, such as phorbol 12-myristate 13-acetate (PMA), mezerein and oleoyl acetylglycerol produced a concentration-dependent potentiation of K(+)-induced release of [3H]5-hydroxytryptamine ([3H]5-HT). Enhanced release was dependent on the concentration of both Ca2+ and K+ in the superfusion medium. Calcium-independent release of [3H]5-HT or release induced by the Ca2+ ionophore were unaffected by PKC activators. Calcium-dependent release of [3H]5-HT, evoked by K+, was enhanced under similar conditions by the L-type Ca2+ channel agonists Bay K 8644 and (+)-SDZ 202-791. Nimodipine, an L-type Ca2+ channel antagonist, while having no independent effect on K(+)-induced release of [3H]5-HT, abolished the potentiative effects of Bay K 8644 and PMA. Similarly, the PKC inhibitors, polymyxin B and staurosporine, blocked effects of both PMA and Bay K 8644 on K(+)-stimulated release of [3H]5-HT. Neither PMA nor Bay K 8644 altered the uptake of [3H]5-HT. These results suggest that PKC-dependent mechanisms utilize calcium influx, via the L-type calcium channel, to modulate release of neurotransmitter and indicate a possible functional link between PKC and L-type voltage-dependent calcium channels in the spinal cord."} {"id": "PMID:1282221", "title": "Capsaicin-like effect of (6)-shogaol on substance P-containing primary afferents of rats: a possible mechanism of its analgesic action.", "content": "The effects of (6)-shogaol, a pungent component of dried ginger with a capsaicin-like chemical structure, on the release of immunoreactive substance P from the spinal dorsal horn were examined by in vitro superfusion of the dorsal-half slices of the spinal cord of the rat. (6)-Shogaol (30 microM to 1 mM) increased dose-dependently the release of immunoreactive substance P. The maximum effect of (6)-shogaol was observed at a concentration of 100 microM and less than a half of the effect of 10 microM capsaicin. The effect of (6)-shogaol (100 microM) was attenuated in slices from rats with dorsal rhizotomy and abolished by elimination of calcium ions from the perfusion medium. Pretreatment with (6)-shogaol in vitro inhibited the capsaicin-evoked release of immunoreactive substance P. On the other hand, systemic administration of (6)-shogaol (160 mg/kg) produced antinociception in rats, with a peak effect between 15 and 30 min and a smaller dose of 80 mg/kg was without effect. Treatment of rats with (6)-shogaol, at a dose of 160 mg/kg but not at 80 mg/kg, for 20 min significantly decreased release of immunoreactive substance P, evoked by capsaicin (10 microM), from the slices of cord. These data suggest that (6)-shogaol shares the sites of action with capsaicin, on the terminals of substance P-containing primary afferents, to release of the neuropeptide and inhibit the release of substance P, by subsequent stimulation of the primary afferents. The latter action of (6)-shogaol might be relevant to its analgesic effect.", "contents": "Capsaicin-like effect of (6)-shogaol on substance P-containing primary afferents of rats: a possible mechanism of its analgesic action. The effects of (6)-shogaol, a pungent component of dried ginger with a capsaicin-like chemical structure, on the release of immunoreactive substance P from the spinal dorsal horn were examined by in vitro superfusion of the dorsal-half slices of the spinal cord of the rat. (6)-Shogaol (30 microM to 1 mM) increased dose-dependently the release of immunoreactive substance P. The maximum effect of (6)-shogaol was observed at a concentration of 100 microM and less than a half of the effect of 10 microM capsaicin. The effect of (6)-shogaol (100 microM) was attenuated in slices from rats with dorsal rhizotomy and abolished by elimination of calcium ions from the perfusion medium. Pretreatment with (6)-shogaol in vitro inhibited the capsaicin-evoked release of immunoreactive substance P. On the other hand, systemic administration of (6)-shogaol (160 mg/kg) produced antinociception in rats, with a peak effect between 15 and 30 min and a smaller dose of 80 mg/kg was without effect. Treatment of rats with (6)-shogaol, at a dose of 160 mg/kg but not at 80 mg/kg, for 20 min significantly decreased release of immunoreactive substance P, evoked by capsaicin (10 microM), from the slices of cord. These data suggest that (6)-shogaol shares the sites of action with capsaicin, on the terminals of substance P-containing primary afferents, to release of the neuropeptide and inhibit the release of substance P, by subsequent stimulation of the primary afferents. The latter action of (6)-shogaol might be relevant to its analgesic effect."} {"id": "PMID:1282222", "title": "Comparison in different tissue preparations of the in vitro pharmacological profile of RP 67580, a new non-peptide substance P antagonist.", "content": "We describe the effects of RP 67580, a new non-peptide substance P (SP) antagonist, on tachykinin-induced contractions of guinea-pig ileum, trachea and urinary bladder, rabbit pulmonary artery and rat portal vein. All NK1 agonists tested (SP, Septide, SPOMe and [Pro9]SP) contracted guinea-pig ileum, trachea and urinary bladder (pD2 = 7.5 to 9.1), but they had no effect on rabbit pulmonary artery or rat portal vein (pD2 < 6). RP 67580 inhibited these effects: guinea-pig ileum, pA2 = 7.1 to 7.6; guinea-pig trachea and urinary bladder, pKB = 6.3 to 6.8. The difference in RP 67580 activity in these tissues might be due to the existence of subtypes of NK1 receptors. RP 67580 (1 microns) did not affect the contractions induced by the two NK2 agonists, NKA and [Lys5, MeLeu9, Nle10]NKA(4-10) (pA2 < 6), except in guinea-pig ileum (pA2 = 7.3-7.5) where these two NK2 agonists interact apparently with NK1 receptors. In the tissue preparations used, RP 67580 (1 micron) was without effect on contractions induced by the NK3 agonists: NKB and senktide. These results indicate the high selectivity for NK1 receptors of RP 67580. In all cases, similar results were obtained with another non-peptide SP antagonist, (+/-) CP-96,345. The present work provides further evidence that RP 67580 and (+/-) CP-96,345 exert in vitro a potent, selective and competitive antagonistic action on NK1 receptors and suggests the existence of at least two distinct NK1 receptor subtypes in some guinea-pig peripheral organs.", "contents": "Comparison in different tissue preparations of the in vitro pharmacological profile of RP 67580, a new non-peptide substance P antagonist. We describe the effects of RP 67580, a new non-peptide substance P (SP) antagonist, on tachykinin-induced contractions of guinea-pig ileum, trachea and urinary bladder, rabbit pulmonary artery and rat portal vein. All NK1 agonists tested (SP, Septide, SPOMe and [Pro9]SP) contracted guinea-pig ileum, trachea and urinary bladder (pD2 = 7.5 to 9.1), but they had no effect on rabbit pulmonary artery or rat portal vein (pD2 < 6). RP 67580 inhibited these effects: guinea-pig ileum, pA2 = 7.1 to 7.6; guinea-pig trachea and urinary bladder, pKB = 6.3 to 6.8. The difference in RP 67580 activity in these tissues might be due to the existence of subtypes of NK1 receptors. RP 67580 (1 microns) did not affect the contractions induced by the two NK2 agonists, NKA and [Lys5, MeLeu9, Nle10]NKA(4-10) (pA2 < 6), except in guinea-pig ileum (pA2 = 7.3-7.5) where these two NK2 agonists interact apparently with NK1 receptors. In the tissue preparations used, RP 67580 (1 micron) was without effect on contractions induced by the NK3 agonists: NKB and senktide. These results indicate the high selectivity for NK1 receptors of RP 67580. In all cases, similar results were obtained with another non-peptide SP antagonist, (+/-) CP-96,345. The present work provides further evidence that RP 67580 and (+/-) CP-96,345 exert in vitro a potent, selective and competitive antagonistic action on NK1 receptors and suggests the existence of at least two distinct NK1 receptor subtypes in some guinea-pig peripheral organs."} {"id": "PMID:1282223", "title": "Immune cell imbalance in major depressive and panic disorders.", "content": "We investigated subsets of peripheral immunologic cells in 12 drug-free patients affected by major depression according to DSM-III-R criteria, and who had recent evidence of somatic diseases. They were compared with 10 drug-free depressives, with 10 patients with panic disorder, and with 12 healthy volunteers, all without somatic disease. The immune subsets were measured by flow cytometry. The results showed that both groups of depressives had the same abnormalities in immune cells compared with the healthy volunteers or the panic disorder patients; in particular they presented a lower number of CD3+, CD8+ and HLA-DR+. The patients with panic attacks did not differ from healthy controls, except for CD4+ cells which were significantly lowered, even in comparison with the depressive groups. These data, although preliminary and in a small sample, suggest that some immune parameters may be influenced by the presence of a major psychiatric disorder.", "contents": "Immune cell imbalance in major depressive and panic disorders. We investigated subsets of peripheral immunologic cells in 12 drug-free patients affected by major depression according to DSM-III-R criteria, and who had recent evidence of somatic diseases. They were compared with 10 drug-free depressives, with 10 patients with panic disorder, and with 12 healthy volunteers, all without somatic disease. The immune subsets were measured by flow cytometry. The results showed that both groups of depressives had the same abnormalities in immune cells compared with the healthy volunteers or the panic disorder patients; in particular they presented a lower number of CD3+, CD8+ and HLA-DR+. The patients with panic attacks did not differ from healthy controls, except for CD4+ cells which were significantly lowered, even in comparison with the depressive groups. These data, although preliminary and in a small sample, suggest that some immune parameters may be influenced by the presence of a major psychiatric disorder."} {"id": "PMID:1282224", "title": "Bilateral innervation of the musculus levator palpebrae superioris by single motoneurons in the monkey.", "content": "The location of motoneurons innervating the musculus levator palpebrae superioris (LPS) was studied in the monkey (Macaca irus) by using Fast blue (FB) and propidium iodide (PI) as retrograde neuronal tracers. In each monkey, FB was injected into the LPS of one eye and PI into the LPS of the other eye. Neuronal cell bodies labeled with FB and/or PI were seen intermixed bilaterally through the entire rostrocaudal extent of the central caudal nucleus. While single-labeled (70%) cell bodies predominated, many double-labeled (30%) cell bodies were also encountered. Each of the double-labeled neurons was concluded to supply the LPS on both sides by way of axon collaterals.", "contents": "Bilateral innervation of the musculus levator palpebrae superioris by single motoneurons in the monkey. The location of motoneurons innervating the musculus levator palpebrae superioris (LPS) was studied in the monkey (Macaca irus) by using Fast blue (FB) and propidium iodide (PI) as retrograde neuronal tracers. In each monkey, FB was injected into the LPS of one eye and PI into the LPS of the other eye. Neuronal cell bodies labeled with FB and/or PI were seen intermixed bilaterally through the entire rostrocaudal extent of the central caudal nucleus. While single-labeled (70%) cell bodies predominated, many double-labeled (30%) cell bodies were also encountered. Each of the double-labeled neurons was concluded to supply the LPS on both sides by way of axon collaterals."} {"id": "PMID:1282225", "title": "Enhancement of the excitatory actions of GABA by barbiturates and benzodiazepines.", "content": "Whole cell recordings from hippocampal CA1 pyramidal neurons using electrode chloride concentrations of 12-80 mM demonstrated that the effect of synaptic activation of GABAA receptors was dependent on the transmembrane chloride gradient. When the chloride reversal potential was positive to action potential threshold, GABAA receptor activation was excitatory, and anticonvulsant barbiturates and benzodiazepines enhanced this excitation. Enhancement of GABAergic excitation of interneurons may contribute to the efficacy of these drugs, while enhancement of GABAergic excitation of principal neurons may be an important mechanism of failure, such as occurs in the treatment of neonatal seizures.", "contents": "Enhancement of the excitatory actions of GABA by barbiturates and benzodiazepines. Whole cell recordings from hippocampal CA1 pyramidal neurons using electrode chloride concentrations of 12-80 mM demonstrated that the effect of synaptic activation of GABAA receptors was dependent on the transmembrane chloride gradient. When the chloride reversal potential was positive to action potential threshold, GABAA receptor activation was excitatory, and anticonvulsant barbiturates and benzodiazepines enhanced this excitation. Enhancement of GABAergic excitation of interneurons may contribute to the efficacy of these drugs, while enhancement of GABAergic excitation of principal neurons may be an important mechanism of failure, such as occurs in the treatment of neonatal seizures."} {"id": "PMID:1282226", "title": "Evans blue reduces macroscopic desensitization of non-NMDA receptor mediated currents and prolongs excitatory postsynaptic currents in cultured rat thalamic neurons.", "content": "Fast application of L-glutamate, AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) or kainate to cultured rat thalamic neurons revealed properties of non-NMDA (N-methyl-D-aspartate) receptors similar to those described in hippocampal neurons. The kinetics of non-NMDA receptor-mediated currents were altered by the addition of the dye Evans Blue (EB). Macroscopic desensitization was reduced and activation and deactivation kinetics were slowed. Delayed addition of EB, after desensitization of non-NMDA receptors, resulted in reactivation of desensitized receptors. Thus, both ion channel gating and entry into the desensitized state were affected. Evans blue also slowed the activation and the decay of glutamatergic miniature EPSCs (excitatory postsynaptic currents), demonstrating that receptor kinetics determine the time course of the synaptic response.", "contents": "Evans blue reduces macroscopic desensitization of non-NMDA receptor mediated currents and prolongs excitatory postsynaptic currents in cultured rat thalamic neurons. Fast application of L-glutamate, AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid) or kainate to cultured rat thalamic neurons revealed properties of non-NMDA (N-methyl-D-aspartate) receptors similar to those described in hippocampal neurons. The kinetics of non-NMDA receptor-mediated currents were altered by the addition of the dye Evans Blue (EB). Macroscopic desensitization was reduced and activation and deactivation kinetics were slowed. Delayed addition of EB, after desensitization of non-NMDA receptors, resulted in reactivation of desensitized receptors. Thus, both ion channel gating and entry into the desensitized state were affected. Evans blue also slowed the activation and the decay of glutamatergic miniature EPSCs (excitatory postsynaptic currents), demonstrating that receptor kinetics determine the time course of the synaptic response."} {"id": "PMID:1282227", "title": "General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex.", "content": "The effects of several general anaesthetics on the responses evoked by the excitatory amino acid agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) were investigated in mouse cortical wedges placed in a two compartment bath and superfused with a nominally Mg(2+)-free Krebs solution. Chloroform (3-6 mM) and halothane (1-3 mM) preferentially antagonized AMPA responses; thiopental (0.1-0.4 mM), diethyl ether (10-30 mM) and isoflurane (1-3 mM) antagonized both AMPA or NMDA responses while ketamine antagonized NMDA responses in a highly selective way. The antagonism of the excitatory amino acid responses exerted by the anaesthetics was non competitive in nature. The inhibition of excitatory amino acid receptor function may be one of the mechanisms whereby general anaesthesia is produced.", "contents": "General anaesthetics inhibit the responses induced by glutamate receptor agonists in the mouse cortex. The effects of several general anaesthetics on the responses evoked by the excitatory amino acid agonists N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) were investigated in mouse cortical wedges placed in a two compartment bath and superfused with a nominally Mg(2+)-free Krebs solution. Chloroform (3-6 mM) and halothane (1-3 mM) preferentially antagonized AMPA responses; thiopental (0.1-0.4 mM), diethyl ether (10-30 mM) and isoflurane (1-3 mM) antagonized both AMPA or NMDA responses while ketamine antagonized NMDA responses in a highly selective way. The antagonism of the excitatory amino acid responses exerted by the anaesthetics was non competitive in nature. The inhibition of excitatory amino acid receptor function may be one of the mechanisms whereby general anaesthesia is produced."} {"id": "PMID:1282228", "title": "Transmitter substances contained in the petrosal ganglion cells determined by a double-labeling method in the rat.", "content": "The presence of glutamate (Glu), aspartate (Asp) and substance P (SP) in the petrosal ganglion of rats anesthetized with pentobarbital sodium was studied using retrograde labeling of the carotid sinus nerve (CSN) with horseradish peroxidase (HRP) in combination with immunohistochemistry. (i) The incidence of HRP/Glu-labeled cells was the highest (32%, n = 3), followed in order by HRP/Asp-labeled cells (23%, n = 3) and HRP/SP-labeled cells (6%, n = 3). (ii) No significant difference was observed in the average diameter of HRP/Glu- and HRP/Asp-labeled cells, but the average diameter of HRP/SP-labeled cells was significantly larger than that of HRP/Glu- and HRP/Asp-labeled cells (P < 0.01). These results suggest that Glu may coexist with Asp, and SP-containing cells may form a different population from Glu- and Asp-containing cells in the petrosal ganglion. The physiological role of these transmitter substances is discussed.", "contents": "Transmitter substances contained in the petrosal ganglion cells determined by a double-labeling method in the rat. The presence of glutamate (Glu), aspartate (Asp) and substance P (SP) in the petrosal ganglion of rats anesthetized with pentobarbital sodium was studied using retrograde labeling of the carotid sinus nerve (CSN) with horseradish peroxidase (HRP) in combination with immunohistochemistry. (i) The incidence of HRP/Glu-labeled cells was the highest (32%, n = 3), followed in order by HRP/Asp-labeled cells (23%, n = 3) and HRP/SP-labeled cells (6%, n = 3). (ii) No significant difference was observed in the average diameter of HRP/Glu- and HRP/Asp-labeled cells, but the average diameter of HRP/SP-labeled cells was significantly larger than that of HRP/Glu- and HRP/Asp-labeled cells (P < 0.01). These results suggest that Glu may coexist with Asp, and SP-containing cells may form a different population from Glu- and Asp-containing cells in the petrosal ganglion. The physiological role of these transmitter substances is discussed."} {"id": "PMID:1282229", "title": "Morphometric and biochemical studies in trigeminal nerve of rat after trichloroethylene or dichloroacetylene oral administration.", "content": "Trigeminal nerve impairment is one of the main features of the clinical spectrum observed after trichloroethylene (Tce) exposure. A morphometric study of teased fibres, an analysis of the fatty acid composition of total lipids of the trigeminal trunk, measurements of myelin basic protein (MBP) and of 2'-3'-cyclic nucleotide 3' phosphohydrolase (CNP) activity were used to characterize this lesion. Furthermore, the effects of Tce and of dichloroacetylene (Dca), a breakdown product supposed to be the main cause of the trigeminal neuropathy, were compared under the same experimental conditions. Results showed a significant decrease of the internode length and of the mean fibre diameter in the Dca group whereas these values, although also diminished, were not significantly affected in the Tce group. In the trigeminal nerve, this was associated with a significant (46%) decrease in sigma. (n-6) fatty acid and a 22% decrease in sigma. (n-3) fatty acid contents in the Tce group whereas these decreases were respectively 32% in sigma. (n-6) fatty acid and 27% (significant) in sigma. (n-3) fatty acid contents in the Dca group. In this group, a 64% increase in sigma. Fatty aldehydes was also observed. Finally, Tce or Dca had only a slight effect on the overall profile of fatty acid content in the brain and no significant variation was observed in MBP level and CNP activity. Both compounds can thus induce trigeminal nerve alterations, but with a higher intensity for Dca.", "contents": "Morphometric and biochemical studies in trigeminal nerve of rat after trichloroethylene or dichloroacetylene oral administration. Trigeminal nerve impairment is one of the main features of the clinical spectrum observed after trichloroethylene (Tce) exposure. A morphometric study of teased fibres, an analysis of the fatty acid composition of total lipids of the trigeminal trunk, measurements of myelin basic protein (MBP) and of 2'-3'-cyclic nucleotide 3' phosphohydrolase (CNP) activity were used to characterize this lesion. Furthermore, the effects of Tce and of dichloroacetylene (Dca), a breakdown product supposed to be the main cause of the trigeminal neuropathy, were compared under the same experimental conditions. Results showed a significant decrease of the internode length and of the mean fibre diameter in the Dca group whereas these values, although also diminished, were not significantly affected in the Tce group. In the trigeminal nerve, this was associated with a significant (46%) decrease in sigma. (n-6) fatty acid and a 22% decrease in sigma. (n-3) fatty acid contents in the Tce group whereas these decreases were respectively 32% in sigma. (n-6) fatty acid and 27% (significant) in sigma. (n-3) fatty acid contents in the Dca group. In this group, a 64% increase in sigma. Fatty aldehydes was also observed. Finally, Tce or Dca had only a slight effect on the overall profile of fatty acid content in the brain and no significant variation was observed in MBP level and CNP activity. Both compounds can thus induce trigeminal nerve alterations, but with a higher intensity for Dca."} {"id": "PMID:1282230", "title": "Clinical, biochemical, electrophysiologic, and histologic assessment of chlorpyrifos induced delayed neuropathy in the cat.", "content": "The ability of a supralethal dose of chlorpyrifos to produce delayed neuropathy was examined using assessments of clinical signs, electromyography (EMG), motor nerve conduction velocity (MNCV), lymphocyte neuropathy target esterase activity (LNTE), and histologic changes in nervous system tissues. Cats were exposed to a single, im injection of corn oil (vehicle control), DFP (positive control) at 5.0 mg/kg, or chlorpyrifos at 300 mg/kg and observed for 60 days. Atropine and 2-PAM were administered to chlorpyrifos exposed cats one to two times a day for 14 to 24 days in response to the appearance of cholinergic signs. Anorectic cats during the acute toxicosis were force fed by hand and hydration was maintained by administering fluids sc. Onset of ataxia (mean +/- SD) for the positive control and chlorpyrifos exposed cats were 16.2 +/- 1.8 days (range of 14-19 days) and 19.0 +/- 1.4 days (range of 17-21 days), respectively. Functional deficits for both groups were confined to the hindlimbs and characterized by a crouched-waddling gait, hypermetria, and proprioceptive deficits. Maximal inhibition of LNTE activity was 96% at 24 hr postdosing in the positive control group and 46% at 7 days postdosing in the chlorpyrifos group. No EMG or MNCV abnormalities were detected in any of the treatment groups. Axonal degeneration was similar for the positive control and chlorpyrifos exposed cats. Ascending tracts of the cervical spinal cord and descending tracts of the thoracic and lumbar spinal cord were most severely affected and peripheral nerves were only mildly affected. The clinical and histologic effects produced indicate that chlorpyrifos can cause delayed neuropathy in the domestic cat. The moderate but prolonged inhibition of LNTE produced by chlorpyrifos is atypical of classic organophosphorus delayed neurotoxicants.", "contents": "Clinical, biochemical, electrophysiologic, and histologic assessment of chlorpyrifos induced delayed neuropathy in the cat. The ability of a supralethal dose of chlorpyrifos to produce delayed neuropathy was examined using assessments of clinical signs, electromyography (EMG), motor nerve conduction velocity (MNCV), lymphocyte neuropathy target esterase activity (LNTE), and histologic changes in nervous system tissues. Cats were exposed to a single, im injection of corn oil (vehicle control), DFP (positive control) at 5.0 mg/kg, or chlorpyrifos at 300 mg/kg and observed for 60 days. Atropine and 2-PAM were administered to chlorpyrifos exposed cats one to two times a day for 14 to 24 days in response to the appearance of cholinergic signs. Anorectic cats during the acute toxicosis were force fed by hand and hydration was maintained by administering fluids sc. Onset of ataxia (mean +/- SD) for the positive control and chlorpyrifos exposed cats were 16.2 +/- 1.8 days (range of 14-19 days) and 19.0 +/- 1.4 days (range of 17-21 days), respectively. Functional deficits for both groups were confined to the hindlimbs and characterized by a crouched-waddling gait, hypermetria, and proprioceptive deficits. Maximal inhibition of LNTE activity was 96% at 24 hr postdosing in the positive control group and 46% at 7 days postdosing in the chlorpyrifos group. No EMG or MNCV abnormalities were detected in any of the treatment groups. Axonal degeneration was similar for the positive control and chlorpyrifos exposed cats. Ascending tracts of the cervical spinal cord and descending tracts of the thoracic and lumbar spinal cord were most severely affected and peripheral nerves were only mildly affected. The clinical and histologic effects produced indicate that chlorpyrifos can cause delayed neuropathy in the domestic cat. The moderate but prolonged inhibition of LNTE produced by chlorpyrifos is atypical of classic organophosphorus delayed neurotoxicants."} {"id": "PMID:1282231", "title": "Intravitreal neovascular tissue of proliferative diabetic retinopathy: an immunohistochemical study.", "content": "Intravitreal neovascular tissue in 8 cases of proliferative diabetic retinopathy was investigated using immunohistochemical techniques. All 8 cases yielded positive immunoreactivity for type II collagen (vitreous collagen). The intravitreal neovascular tissue was classified into two groups (A or B), depending upon the distribution of type II collagen. In group A (3 cases), blood vessels were entirely surrounded by vitreous collagen, and in group B (5 cases), the vessels proliferated on one side of a mass of vitreous collagen. Type I and III collagens were distributed diffusely within the extracellular space of the tissue, whereas type IV collagen and fibronectin (FN) formed a basement membrane-like foundation for the newly formed vessels. Glial fibrillary acidic protein (GFAP)-immunoreactive cells were not clearly detected in any of the cases. Neovascular tissue typically proliferated on the posterior vitreous surface (as found in group B), but was also found to penetrate the vitreous gel (as found in group A). As neovascular tissue proliferation proceeded, types I, III and IV collagens and FN were produced. Glial cells (GFAP-positive cells) were not essential for neovascular tissue formation.", "contents": "Intravitreal neovascular tissue of proliferative diabetic retinopathy: an immunohistochemical study. Intravitreal neovascular tissue in 8 cases of proliferative diabetic retinopathy was investigated using immunohistochemical techniques. All 8 cases yielded positive immunoreactivity for type II collagen (vitreous collagen). The intravitreal neovascular tissue was classified into two groups (A or B), depending upon the distribution of type II collagen. In group A (3 cases), blood vessels were entirely surrounded by vitreous collagen, and in group B (5 cases), the vessels proliferated on one side of a mass of vitreous collagen. Type I and III collagens were distributed diffusely within the extracellular space of the tissue, whereas type IV collagen and fibronectin (FN) formed a basement membrane-like foundation for the newly formed vessels. Glial fibrillary acidic protein (GFAP)-immunoreactive cells were not clearly detected in any of the cases. Neovascular tissue typically proliferated on the posterior vitreous surface (as found in group B), but was also found to penetrate the vitreous gel (as found in group A). As neovascular tissue proliferation proceeded, types I, III and IV collagens and FN were produced. Glial cells (GFAP-positive cells) were not essential for neovascular tissue formation."} {"id": "PMID:1282232", "title": "Mass cultivation of human retinal pigment epithelial cells with microcarrier.", "content": "Microcarrier cell culture permits mass cultivation of anchorage-dependent cells. In this study, mass cultivation of human retinal pigment epithelial (RPE) cells was studied using Cytodex 3 (Pharmacia) as a microcarrier. Human RPE cells were established from aborted fetuses and cultured in Dulbecco's modified Eagle's Medium (DMEM). After the 3rd-5th passages, RPE cells were suspended in 50 ml of DMEM in a spinner flask at a density of 2 x 10(5)/ml, and Cytodex 3 was added to the spinner flask at a bead density of 10 mg/ml. Cultures were maintained at 20-50 rpm (final speed) on a magnetic stirrer, and DMEM was added up to 100 ml. Fifty milliliters of DMEM were decanted and replaced with fresh DMEM every 2 days. After 1 week, a cell density of 10(6)/ml DMEM was obtained. Phase contrast microscopy showed bridging formation between microcarriers, which suggests tight cell adhesion. Microcarrier cell culture has a variety of advantages which include greater cell production, use of less medium and less risk of contamination compared to the conventional monolayer culture technique, and it also allows passaging without using proteases. Using this culture system, greater possibilities for wider application of new cell cultures can be expected.", "contents": "Mass cultivation of human retinal pigment epithelial cells with microcarrier. Microcarrier cell culture permits mass cultivation of anchorage-dependent cells. In this study, mass cultivation of human retinal pigment epithelial (RPE) cells was studied using Cytodex 3 (Pharmacia) as a microcarrier. Human RPE cells were established from aborted fetuses and cultured in Dulbecco's modified Eagle's Medium (DMEM). After the 3rd-5th passages, RPE cells were suspended in 50 ml of DMEM in a spinner flask at a density of 2 x 10(5)/ml, and Cytodex 3 was added to the spinner flask at a bead density of 10 mg/ml. Cultures were maintained at 20-50 rpm (final speed) on a magnetic stirrer, and DMEM was added up to 100 ml. Fifty milliliters of DMEM were decanted and replaced with fresh DMEM every 2 days. After 1 week, a cell density of 10(6)/ml DMEM was obtained. Phase contrast microscopy showed bridging formation between microcarriers, which suggests tight cell adhesion. Microcarrier cell culture has a variety of advantages which include greater cell production, use of less medium and less risk of contamination compared to the conventional monolayer culture technique, and it also allows passaging without using proteases. Using this culture system, greater possibilities for wider application of new cell cultures can be expected."} {"id": "PMID:1282233", "title": "[Informative value of varying serum alpha fetoprotein levels in pregnant women based on a screening program in a Hungarian institute. What next?].", "content": "The authors evaluated the maternal serum alfa fetoprotein screening data of 3 years period. Out the neural tube defects they observed increased values at 20% of another congenital malformations. At the pregnant having abnormal serum alfa fetoprotein significantly accumulated the late-term abortion, stillbirth and preterm delivery. At the mothers of stillborns and abortions frequently noticed the different values. They direct attention to the fetal-living-danger importance, control functions of the abnormal level and after prospective data collection it may have new aspecific alarm role too. Accordingly the maternal serum alfa fetoprotein may consider like fetal blood sediment examination.", "contents": "[Informative value of varying serum alpha fetoprotein levels in pregnant women based on a screening program in a Hungarian institute. What next?]. The authors evaluated the maternal serum alfa fetoprotein screening data of 3 years period. Out the neural tube defects they observed increased values at 20% of another congenital malformations. At the pregnant having abnormal serum alfa fetoprotein significantly accumulated the late-term abortion, stillbirth and preterm delivery. At the mothers of stillborns and abortions frequently noticed the different values. They direct attention to the fetal-living-danger importance, control functions of the abnormal level and after prospective data collection it may have new aspecific alarm role too. Accordingly the maternal serum alfa fetoprotein may consider like fetal blood sediment examination."} {"id": "PMID:1282235", "title": "Identification of editing positions in the ndhB transcript from maize chloroplasts reveals sequence similarities between editing sites of chloroplasts and plant mitochondria.", "content": "A comparison of the nucleotide sequences from genomic DNA and cDNA of the ndhB gene from maize chloroplasts shows that the ndhB transcript is edited by C-to-U transitions at six positions which appear to exist as editing sites also in the chloroplast ndhB genes from rice and tobacco but not from liverwort. In order to identify possible sequence determinants necessary for editing, the sequences surrounding the newly identified ndhB and previously identified ndhA editing sites were compared with each other and with editing sites observed in plant mitochondrial transcripts. Among the chloroplast editing sites two closely positioned ndhB sites show similarity by sharing a common octanucleotide. The existence of the identical octanucleotide in the ndhJ gene whose transcript is not edited at the respective position, shows, however, that this octanucleotide is not sufficient to elicit the editing process. On the other hand, several of the chloroplast editing sites show sequence similarities with certain sets of consensus sequences reported earlier for editing sites of plant mitochondria. This supports the view that the editing processes of both plant organelles share common components and/or mechanistic steps and that the consensus sequences are part of the determinants necessary for editing.", "contents": "Identification of editing positions in the ndhB transcript from maize chloroplasts reveals sequence similarities between editing sites of chloroplasts and plant mitochondria. A comparison of the nucleotide sequences from genomic DNA and cDNA of the ndhB gene from maize chloroplasts shows that the ndhB transcript is edited by C-to-U transitions at six positions which appear to exist as editing sites also in the chloroplast ndhB genes from rice and tobacco but not from liverwort. In order to identify possible sequence determinants necessary for editing, the sequences surrounding the newly identified ndhB and previously identified ndhA editing sites were compared with each other and with editing sites observed in plant mitochondrial transcripts. Among the chloroplast editing sites two closely positioned ndhB sites show similarity by sharing a common octanucleotide. The existence of the identical octanucleotide in the ndhJ gene whose transcript is not edited at the respective position, shows, however, that this octanucleotide is not sufficient to elicit the editing process. On the other hand, several of the chloroplast editing sites show sequence similarities with certain sets of consensus sequences reported earlier for editing sites of plant mitochondria. This supports the view that the editing processes of both plant organelles share common components and/or mechanistic steps and that the consensus sequences are part of the determinants necessary for editing."} {"id": "PMID:1282236", "title": "New data concerning the functional organization of the mammalian cell nucleolus: detection of RNA and rRNA by in situ molecular immunocytochemistry.", "content": "We have investigated the fine spatial distribution of RNA and rRNA within the Ehrlich tumor cell nucleolus by in situ hybridization with a biotin-labeled probe and by two new strategies, the polyadenylate nucleotidyl transferase-immunogold technique and immuno-labeling with anti-RNA antibodies. Besides the presence, as expected, of RNA and rRNA in the granular component and the dense fibrillar component, we show, for the first time, significant label over all the fibrillar centers of the nucleoli. When RNA and DNA were detected simultaneously on the same sections, only the fibrillar centers were positive for both. These results throw light on the controversial subject of the precise location of transcribing rRNA genes within the nucleolus. The fibrillar centers, and not the dense fibrillar component, should thus be the site of rRNA synthesis.", "contents": "New data concerning the functional organization of the mammalian cell nucleolus: detection of RNA and rRNA by in situ molecular immunocytochemistry. We have investigated the fine spatial distribution of RNA and rRNA within the Ehrlich tumor cell nucleolus by in situ hybridization with a biotin-labeled probe and by two new strategies, the polyadenylate nucleotidyl transferase-immunogold technique and immuno-labeling with anti-RNA antibodies. Besides the presence, as expected, of RNA and rRNA in the granular component and the dense fibrillar component, we show, for the first time, significant label over all the fibrillar centers of the nucleoli. When RNA and DNA were detected simultaneously on the same sections, only the fibrillar centers were positive for both. These results throw light on the controversial subject of the precise location of transcribing rRNA genes within the nucleolus. The fibrillar centers, and not the dense fibrillar component, should thus be the site of rRNA synthesis."} {"id": "PMID:1282237", "title": "Quantitation of human cellular retinoic acid-binding protein II (CRABP-II) RNA from cultured human skin fibroblast cells and human skin biopsies treated with retinoic acid.", "content": "A polymerase chain reaction (PCR) method has been validated for the quantitation of retinoic acid (RA) induction of cellular retinoic acid-binding protein II (CRABP-II) RNA from cultured human skin fibroblasts and human skin biopsies. The method utilizes reverse transcription and PCR (RT-PCR) to compare cellular CRABP-II RNA with a known amount of added internal standard RNA generated from a modified CRABP-II cDNA containing a 42 bp deletion. Thus, after RT-PCR of cellular and standard CRABP-II RNA in the same tube, the resulting DNA bands could be distinguished by size on ethidium bromide-stained, nondenaturing polyacrylamide gel. Serial dilutions of cellular RNA were co-amplified with a fixed amount of internal standard CRABP-II RNA, and the ratio of intensities of the two DNA bands was determined by computerized image analysis of the gel photograph. A linear relationship was found between the logs of this ratio and the input RNA. Absolute quantitation of cellular CRABP-II RNA was determined from the 'equivalence point', the dilution at which band intensities from cellular and standard RNAs were identical. Using this quantitative assay, the amount of CRABP-II RNA in cultured fibroblasts was 24 attomoles per microgram total RNA. A 4.2-fold increase in CRABP-II RNA was seen following 24 hours treatment with 10(-6) M RA. CRABP-II RNA content in skin biopsies taken from 3 human subjects ranged from 16 to 25 attomole/micrograms RNA. Topical treatment with 0.1% RA cream resulted in induction ranging from 3.9- to 12-fold over vehicle treatment. The method described here offers a rapid, sensitive and quantitative assay of specific RNAs, and should be especially useful for the measurement of RNA levels from small solid-tissue biopsies.", "contents": "Quantitation of human cellular retinoic acid-binding protein II (CRABP-II) RNA from cultured human skin fibroblast cells and human skin biopsies treated with retinoic acid. A polymerase chain reaction (PCR) method has been validated for the quantitation of retinoic acid (RA) induction of cellular retinoic acid-binding protein II (CRABP-II) RNA from cultured human skin fibroblasts and human skin biopsies. The method utilizes reverse transcription and PCR (RT-PCR) to compare cellular CRABP-II RNA with a known amount of added internal standard RNA generated from a modified CRABP-II cDNA containing a 42 bp deletion. Thus, after RT-PCR of cellular and standard CRABP-II RNA in the same tube, the resulting DNA bands could be distinguished by size on ethidium bromide-stained, nondenaturing polyacrylamide gel. Serial dilutions of cellular RNA were co-amplified with a fixed amount of internal standard CRABP-II RNA, and the ratio of intensities of the two DNA bands was determined by computerized image analysis of the gel photograph. A linear relationship was found between the logs of this ratio and the input RNA. Absolute quantitation of cellular CRABP-II RNA was determined from the 'equivalence point', the dilution at which band intensities from cellular and standard RNAs were identical. Using this quantitative assay, the amount of CRABP-II RNA in cultured fibroblasts was 24 attomoles per microgram total RNA. A 4.2-fold increase in CRABP-II RNA was seen following 24 hours treatment with 10(-6) M RA. CRABP-II RNA content in skin biopsies taken from 3 human subjects ranged from 16 to 25 attomole/micrograms RNA. Topical treatment with 0.1% RA cream resulted in induction ranging from 3.9- to 12-fold over vehicle treatment. The method described here offers a rapid, sensitive and quantitative assay of specific RNAs, and should be especially useful for the measurement of RNA levels from small solid-tissue biopsies."} {"id": "PMID:1282238", "title": "A phosphorothioate at the 3' splice-site inhibits the second splicing step in a group I intron.", "content": "RNA polymerases can synthesize RNA containing phosphorothioate linkages in which a sulfur replaces one of the nonbridging oxygens. Only the Rp isomer is generated during transcription. A Rp phosphorothioate at the 5' splice-site of the Tetrahymena group I intron does not inhibit splicing (McSwiggen, J.A. and Cech, T.R. (1989) Science 244, 679). Transcription of mutants in which the first base of the 3' exon, U+1, was mutated to C or G, in the presence, respectively, of either cytosine or guanosine thiotriphosphate, introduced a phosphorothioate at the 3' splice-site. In both cases exon ligation was blocked. In the phosphorothioate substituted U+1G mutant, a new 3' splice-site was selected one base downstream of the correct site; despite the fact that the correct site was selected with very high fidelity in unsubstituted RNA. In contrast, the exon ligation reaction was successfully performed in reverse using unsubstituted intron RNA and ligated exons containing an Rp phosphorothioate at the exon junction site. Chirality was reversed during transesterification as in 5' splice-site cleavage (vide supra). This suggests that one non-bridging oxygen is particularly crucial for both splicing reactions.", "contents": "A phosphorothioate at the 3' splice-site inhibits the second splicing step in a group I intron. RNA polymerases can synthesize RNA containing phosphorothioate linkages in which a sulfur replaces one of the nonbridging oxygens. Only the Rp isomer is generated during transcription. A Rp phosphorothioate at the 5' splice-site of the Tetrahymena group I intron does not inhibit splicing (McSwiggen, J.A. and Cech, T.R. (1989) Science 244, 679). Transcription of mutants in which the first base of the 3' exon, U+1, was mutated to C or G, in the presence, respectively, of either cytosine or guanosine thiotriphosphate, introduced a phosphorothioate at the 3' splice-site. In both cases exon ligation was blocked. In the phosphorothioate substituted U+1G mutant, a new 3' splice-site was selected one base downstream of the correct site; despite the fact that the correct site was selected with very high fidelity in unsubstituted RNA. In contrast, the exon ligation reaction was successfully performed in reverse using unsubstituted intron RNA and ligated exons containing an Rp phosphorothioate at the exon junction site. Chirality was reversed during transesterification as in 5' splice-site cleavage (vide supra). This suggests that one non-bridging oxygen is particularly crucial for both splicing reactions."} {"id": "PMID:1282239", "title": "The strands of both polarities of a small circular RNA from carnation self-cleave in vitro through alternative double- and single-hammerhead structures.", "content": "The sequence of a circular RNA from carnation has been determined and found to consist of 275 nucleotide residues adopting a branched secondary structure of minimum free energy. Both plus and minus strands of this RNA can form the hammerhead structures proposed to mediate the in vitro self-cleavage of a number of small infectious plant RNAs and the transcript of satellite 2 DNA from the newt. Minus full- and partial-length transcripts of the carnation circular RNA including the hammerhead structure showed self-cleavage during transcription and after purification, indicating the involvement of a single-hammerhead structure in the self-cleavage reaction. In the case of the plus transcripts only a dimeric RNA, but not a monomeric one, self-cleaved efficiently during transcription and after purification, strongly supporting the implication in this process of a double-hammerhead structure theoretically more stable than the corresponding single cleavage domain. However, a plus monomeric transcript self-cleaved after purification at a slow rate in a concentration-independent reaction which most probably occurs through an intramolecular mechanism. Comparative sequence analysis has revealed that the circular RNA from carnation shares similarities with some representative members of the viroid and viroid-like satellites RNAs from plants, suggesting that it is a new member of either these two groups of small pathogenic RNAs.", "contents": "The strands of both polarities of a small circular RNA from carnation self-cleave in vitro through alternative double- and single-hammerhead structures. The sequence of a circular RNA from carnation has been determined and found to consist of 275 nucleotide residues adopting a branched secondary structure of minimum free energy. Both plus and minus strands of this RNA can form the hammerhead structures proposed to mediate the in vitro self-cleavage of a number of small infectious plant RNAs and the transcript of satellite 2 DNA from the newt. Minus full- and partial-length transcripts of the carnation circular RNA including the hammerhead structure showed self-cleavage during transcription and after purification, indicating the involvement of a single-hammerhead structure in the self-cleavage reaction. In the case of the plus transcripts only a dimeric RNA, but not a monomeric one, self-cleaved efficiently during transcription and after purification, strongly supporting the implication in this process of a double-hammerhead structure theoretically more stable than the corresponding single cleavage domain. However, a plus monomeric transcript self-cleaved after purification at a slow rate in a concentration-independent reaction which most probably occurs through an intramolecular mechanism. Comparative sequence analysis has revealed that the circular RNA from carnation shares similarities with some representative members of the viroid and viroid-like satellites RNAs from plants, suggesting that it is a new member of either these two groups of small pathogenic RNAs."} {"id": "PMID:1282240", "title": "Analysis of the gene encoding the RNA subunit of ribonuclease P from cyanobacteria.", "content": "The genes encoding the RNA subunit of ribonuclease P from the unicellular cyanobacterium Synechocystis sp. PCC 6803, and from the heterocyst-forming strains Anabaena sp. PCC 7120 and Calothrix sp. PCC 7601 were cloned using the homologous gene from Anacystis nidulans (Synechococcus sp. PCC 6301) as a probe. The genes and the flanking regions were sequenced. The genes from Anabaena and Calothrix are flanked at their 3'-ends by short tandemly repeated repetitive (STRR) sequences. In addition, two other sets of STRR sequences were detected within the transcribed regions of the Anabaena and Calothrix genes, increasing the length of a variable secondary structure element present in many RNA subunits of ribonuclease P from eubacteria. The ends of the mature RNAs were determined by primer extension and RNase protection. The predicted secondary structure of the three RNAs studied is similar to that of Anacystis and although some idiosyncrasies are observed, fits well with the eubacterial consensus.", "contents": "Analysis of the gene encoding the RNA subunit of ribonuclease P from cyanobacteria. The genes encoding the RNA subunit of ribonuclease P from the unicellular cyanobacterium Synechocystis sp. PCC 6803, and from the heterocyst-forming strains Anabaena sp. PCC 7120 and Calothrix sp. PCC 7601 were cloned using the homologous gene from Anacystis nidulans (Synechococcus sp. PCC 6301) as a probe. The genes and the flanking regions were sequenced. The genes from Anabaena and Calothrix are flanked at their 3'-ends by short tandemly repeated repetitive (STRR) sequences. In addition, two other sets of STRR sequences were detected within the transcribed regions of the Anabaena and Calothrix genes, increasing the length of a variable secondary structure element present in many RNA subunits of ribonuclease P from eubacteria. The ends of the mature RNAs were determined by primer extension and RNase protection. The predicted secondary structure of the three RNAs studied is similar to that of Anacystis and although some idiosyncrasies are observed, fits well with the eubacterial consensus."} {"id": "PMID:1282242", "title": "Feasibility of an implantable arrhythmia monitor.", "content": "Conventional Holter monitoring is of limited benefit in patients with infrequent symptoms suspected to be related to arrhythmia. A small recorder implanted subcutaneously might obviate many limitations of conventional monitoring. To determine the feasibility of obtaining adequate electrocardiographic signals from such a device, a prototype was temporarily implanted in 17 patients undergoing pacemaker implantation. The prototype contained four disc-shaped titanium electrodes, 0.21 inches in diameter embedded in epoxy. The four electrodes were in a square configuration spaced 0.72 inches center to center and were placed face down in a subcutaneous pocket in the left pectoral region. Bipolar recordings were made from a horizontal pair, a vertical pair, and both diagonal paris of electrodes (interelectrode distance 1.02 inches) and recorded on electromagnetic tape after filtering at 0.5-250 Hz. The mean peak-to-peak amplitude in each configuration was determined over a five-beat interval. Clear recordings were obtained from all 17 patients with recognizable P, QRS, and T waves. The amplitude of the signals obtained from the diagonal pairs of electrodes (175 +/- 51 and 170 +/- 54 microV) were greater than obtained from either the vertical pair (142 +/- 62 microV, P = 0.08 compared to diagonal electrodes) or the horizontal pair of electrodes (105 +/- 54 microV, P < 0.01). The maximum amplitude recorded from any configuration was 189 +/- 54 microV. In six patients the device was also tested with the electrodes face up in the subcutaneous pocket.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Feasibility of an implantable arrhythmia monitor. Conventional Holter monitoring is of limited benefit in patients with infrequent symptoms suspected to be related to arrhythmia. A small recorder implanted subcutaneously might obviate many limitations of conventional monitoring. To determine the feasibility of obtaining adequate electrocardiographic signals from such a device, a prototype was temporarily implanted in 17 patients undergoing pacemaker implantation. The prototype contained four disc-shaped titanium electrodes, 0.21 inches in diameter embedded in epoxy. The four electrodes were in a square configuration spaced 0.72 inches center to center and were placed face down in a subcutaneous pocket in the left pectoral region. Bipolar recordings were made from a horizontal pair, a vertical pair, and both diagonal paris of electrodes (interelectrode distance 1.02 inches) and recorded on electromagnetic tape after filtering at 0.5-250 Hz. The mean peak-to-peak amplitude in each configuration was determined over a five-beat interval. Clear recordings were obtained from all 17 patients with recognizable P, QRS, and T waves. The amplitude of the signals obtained from the diagonal pairs of electrodes (175 +/- 51 and 170 +/- 54 microV) were greater than obtained from either the vertical pair (142 +/- 62 microV, P = 0.08 compared to diagonal electrodes) or the horizontal pair of electrodes (105 +/- 54 microV, P < 0.01). The maximum amplitude recorded from any configuration was 189 +/- 54 microV. In six patients the device was also tested with the electrodes face up in the subcutaneous pocket.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282243", "title": "Permanent pacemaker implantation in the cardiac catheterization laboratory versus the operating room: an analysis of hospital charges and complications.", "content": "Permanent pacemakers may be implanted in operating rooms, special procedure laboratories, or cardiac catheterization laboratories. Previous investigators have shown no difference in efficacy or complications in the operating room versus the cardiac catheterization laboratory. We retrospectively analyzed the hospital bills of 30 patients undergoing permanent pacemaker implantation at our institution. Group I was 15 consecutive patients implanted in the operating room and group II was 15 consecutive patients implanted in the cardiac catheterization laboratory, all by the same operators. Hospital charges that were specific to the site of implantation were analyzed. Physician charges for implantation, anesthesiologist, and radiologist charges were not analyzed. There were no in-hospital complications in either group. The mean charges for group I were $1,856.00 and group II were $1,075.00 (P < 0.001). We conclude that implantation of permanent pacemakers in the cardiac catheterization laboratory is associated with significantly lower hospital charges compared to implantation in the operating room and has an equally low complication rate.", "contents": "Permanent pacemaker implantation in the cardiac catheterization laboratory versus the operating room: an analysis of hospital charges and complications. Permanent pacemakers may be implanted in operating rooms, special procedure laboratories, or cardiac catheterization laboratories. Previous investigators have shown no difference in efficacy or complications in the operating room versus the cardiac catheterization laboratory. We retrospectively analyzed the hospital bills of 30 patients undergoing permanent pacemaker implantation at our institution. Group I was 15 consecutive patients implanted in the operating room and group II was 15 consecutive patients implanted in the cardiac catheterization laboratory, all by the same operators. Hospital charges that were specific to the site of implantation were analyzed. Physician charges for implantation, anesthesiologist, and radiologist charges were not analyzed. There were no in-hospital complications in either group. The mean charges for group I were $1,856.00 and group II were $1,075.00 (P < 0.001). We conclude that implantation of permanent pacemakers in the cardiac catheterization laboratory is associated with significantly lower hospital charges compared to implantation in the operating room and has an equally low complication rate."} {"id": "PMID:1282244", "title": "Adenosine and verapamil-sensitive ventricular tachycardia originating from the left ventricle: radiofrequency catheter ablation.", "content": "A ventricular tachycardia (VT) with right bundle branch block (RBBB) QRS morphology and left axis originating from the inferoapical segment of the left ventricle is described in a 49-year-old man without structural heart disease. This VT could be initiated during isoproterenol infusion and was terminated with intravenous administration of adenosine and verapamil. Radiofrequency ablation eliminated the tachycardia. Previous reports have suggested reentry as the mechanism for a verapamil-sensitive VT with this ECG morphology, while cAMP-mediated triggered activity has been proposed as a mechanism for VTs sensitive to adenosine. The latter more typically arise in the right ventricular outflow tract. The electrophysiological and electropharmacological characteristics of the tachycardia in this patient suggest that this VT morphology is not specific for a mechanism but rather for the location of the site of origin.", "contents": "Adenosine and verapamil-sensitive ventricular tachycardia originating from the left ventricle: radiofrequency catheter ablation. A ventricular tachycardia (VT) with right bundle branch block (RBBB) QRS morphology and left axis originating from the inferoapical segment of the left ventricle is described in a 49-year-old man without structural heart disease. This VT could be initiated during isoproterenol infusion and was terminated with intravenous administration of adenosine and verapamil. Radiofrequency ablation eliminated the tachycardia. Previous reports have suggested reentry as the mechanism for a verapamil-sensitive VT with this ECG morphology, while cAMP-mediated triggered activity has been proposed as a mechanism for VTs sensitive to adenosine. The latter more typically arise in the right ventricular outflow tract. The electrophysiological and electropharmacological characteristics of the tachycardia in this patient suggest that this VT morphology is not specific for a mechanism but rather for the location of the site of origin."} {"id": "PMID:1282245", "title": "New concept in activity-controlled pacemakers: clinical results with an accelerometer-based rate adaptive pacing system.", "content": "An accelerometer-based rate adaptive generator (EXCEL VR) has been introduced. A preclinical group of 22 subjects with strap-on devices was observed and reported. A clinical protocol including observation of rate adaptive response to typical daily activities and incremental exercise on a treadmill was administered in seven implanted patients. Indications for implantation in these patients was either second- or third-degree atrioventricular block (five patients, VVIR pacing mode) and sick sinus syndrome (two patients, AAIR pacing mode). Mean pacing rates were 50 ppm (supine), 56 ppm (standing), 77 ppm (descending the stairs), 81 ppm (slow walk), 83 ppm (slow stair climb), 91 ppm (fast walk), and 92 ppm (fast stair climb). When the arm proximal to the pulse generator was exercised, the rate rose to 92 ppm. When the distal arm was strained, the rate was 63 ppm. During treadmill testing, rates between 82 ppm (2 km/hour) and 104 ppm (5 km/hour) were observed. This accelerometer-based rate adaptive pulse generator provided a proportional response to graded activities of treadmill exercise and daily living in these groups of preclinical and clinical subjects.", "contents": "New concept in activity-controlled pacemakers: clinical results with an accelerometer-based rate adaptive pacing system. An accelerometer-based rate adaptive generator (EXCEL VR) has been introduced. A preclinical group of 22 subjects with strap-on devices was observed and reported. A clinical protocol including observation of rate adaptive response to typical daily activities and incremental exercise on a treadmill was administered in seven implanted patients. Indications for implantation in these patients was either second- or third-degree atrioventricular block (five patients, VVIR pacing mode) and sick sinus syndrome (two patients, AAIR pacing mode). Mean pacing rates were 50 ppm (supine), 56 ppm (standing), 77 ppm (descending the stairs), 81 ppm (slow walk), 83 ppm (slow stair climb), 91 ppm (fast walk), and 92 ppm (fast stair climb). When the arm proximal to the pulse generator was exercised, the rate rose to 92 ppm. When the distal arm was strained, the rate was 63 ppm. During treadmill testing, rates between 82 ppm (2 km/hour) and 104 ppm (5 km/hour) were observed. This accelerometer-based rate adaptive pulse generator provided a proportional response to graded activities of treadmill exercise and daily living in these groups of preclinical and clinical subjects."} {"id": "PMID:1282246", "title": "Reversible late potentials due to ischemia.", "content": "The role of ischemia in the development of reversible late potentials was assessed in 19 patients undergoing percutaneous transluminal coronary angioplasty. Signal-averaged electrocardiograms were performed before angioplasty, during ischemia caused by balloon inflation and after angioplasty. Five of 19 patients developed late potentials that reverted to normal after angioplasty. Age, sex, ejection fraction, left ventricular end diastolic pressure, vessels involved, and extent of myocardium in jeopardy did not predict the development of late potentials. Patients with a prior history of myocardial infarction were more likely to develop late potentials. Therefore, patients with prior myocardial infarction appear more likely to develop the substrate for reentrant ventricular tachycardia during periods of ischemia.", "contents": "Reversible late potentials due to ischemia. The role of ischemia in the development of reversible late potentials was assessed in 19 patients undergoing percutaneous transluminal coronary angioplasty. Signal-averaged electrocardiograms were performed before angioplasty, during ischemia caused by balloon inflation and after angioplasty. Five of 19 patients developed late potentials that reverted to normal after angioplasty. Age, sex, ejection fraction, left ventricular end diastolic pressure, vessels involved, and extent of myocardium in jeopardy did not predict the development of late potentials. Patients with a prior history of myocardial infarction were more likely to develop late potentials. Therefore, patients with prior myocardial infarction appear more likely to develop the substrate for reentrant ventricular tachycardia during periods of ischemia."} {"id": "PMID:1282247", "title": "Two different reentrant circuits of ventricular tachycardia in a patient with an extensive anterior infarction: evaluation using electrical catheter ablation techniques.", "content": "Two morphologically distinct sustained ventricular tachycardias were initiated by programmed stimulation during attempted catheter ablation in a patient with an old anterior myocardial infarction. Right bundle branch block configuration of ventricular tachycardia, which was identical to the spontaneously occurring tachycardia, was initiated and displayed fragmented mid-diastolic potential at the apicolateral left ventricular site. Evidence of a critical slow conduction area was observed during delivery of electrical stimuli to this area. Following a 150-joule electrical shock delivered to this area, right bundle branch block pattern of ventricular tachycardia was no longer inducible but a new sustained monomorphic ventricular tachycardia with left bundle branch block pattern was initiated. The mid-diastolic fragmented activity at the ablation site became electrical activation of bystander area that was not participating in the left bundle branch block type of the ventricular tachycardia circuit. The critical slow conduction area was identified at the apicoseptal left ventricular site that was separated more than 5 cm from the ablation site. We speculate that two morphologically distinct sustained monomorphic ventricular tachycardias may be due to two different reentrant circuits and not the different expression of the same circuit.", "contents": "Two different reentrant circuits of ventricular tachycardia in a patient with an extensive anterior infarction: evaluation using electrical catheter ablation techniques. Two morphologically distinct sustained ventricular tachycardias were initiated by programmed stimulation during attempted catheter ablation in a patient with an old anterior myocardial infarction. Right bundle branch block configuration of ventricular tachycardia, which was identical to the spontaneously occurring tachycardia, was initiated and displayed fragmented mid-diastolic potential at the apicolateral left ventricular site. Evidence of a critical slow conduction area was observed during delivery of electrical stimuli to this area. Following a 150-joule electrical shock delivered to this area, right bundle branch block pattern of ventricular tachycardia was no longer inducible but a new sustained monomorphic ventricular tachycardia with left bundle branch block pattern was initiated. The mid-diastolic fragmented activity at the ablation site became electrical activation of bystander area that was not participating in the left bundle branch block type of the ventricular tachycardia circuit. The critical slow conduction area was identified at the apicoseptal left ventricular site that was separated more than 5 cm from the ablation site. We speculate that two morphologically distinct sustained monomorphic ventricular tachycardias may be due to two different reentrant circuits and not the different expression of the same circuit."} {"id": "PMID:1282248", "title": "A degenerative lesion of the approach to the atrioventricular node producing second-degree and third-degree atrioventricular block.", "content": "We report a case of a degenerative approach lesion in an 83-year-old male with diabetes mellitus, hypertension, and ischemic heart disease. His ECGs changed from first-degree atrioventricular (AV) block 14 years ago, to third-degree AV (A-H) block. A pacemaker was implanted for bradycardia. He died 4 years later from heart and renal failure. Serial sections through the conduction system revealed total depletion and fatty replacement of the atrial muscle at the approaches to the AV node.", "contents": "A degenerative lesion of the approach to the atrioventricular node producing second-degree and third-degree atrioventricular block. We report a case of a degenerative approach lesion in an 83-year-old male with diabetes mellitus, hypertension, and ischemic heart disease. His ECGs changed from first-degree atrioventricular (AV) block 14 years ago, to third-degree AV (A-H) block. A pacemaker was implanted for bradycardia. He died 4 years later from heart and renal failure. Serial sections through the conduction system revealed total depletion and fatty replacement of the atrial muscle at the approaches to the AV node."} {"id": "PMID:1282249", "title": "Physiology of \"atypical\" atrioventricular junctional reentrant tachycardia occurring following radiofrequency catheter modification of the atrioventricular node.", "content": "The physiology of atypical atrioventricular junctional reentrant tachycardia (AVJRT) occurring following catheter modification of the AV node is poorly defined. Six patients undergoing radiofrequency current catheter modification of the AV node had inducible atypical AVJRT before or after AV nodal modification. Typical AVJRT was differentiated from atypical AVJRT by a ventriculoatrial (VA) time < 60 msec in the His-bundle electrogram recording. Five of six patients had typical AVJRT and two had atypical AVJRT prior to AV nodal modification. Following anterior approach AV nodal modification, previously undetected atypical AVJRT was induced in four patients. Earliest retrograde atrial activation in the posterior septum was documented in all patients with atypical AVJRT prior to modification and in three of four patients with atypical AVJRT following modification. The AH intervals during tachycardia were 320 +/- 52 msec in typical AVJRT, 88 +/- 33 msec in the premodification atypical AVJRTs, and 172 +/- 12 msec in the postmodification atypical AVJRTs (P = 0.0001). The AH/HA ratios were 4.1 +/- 0.9 in typical AVJRT, 0.5 +/- 0.2 in the premodification atypical AVJRTs, and 0.9 +/- 0.2 in the postmodification atypical AVJRTs (P = 0.0001). Two patients with postmodification atypical AVJRT underwent further posterior approach AV node modification that resulted in VA block. One patient with postmodification atypical AVJRT had further anterior approach AV nodal modification that resulted in heart block. The retrograde limb of the atypical AVJRT seen following anterior approach AV nodal modification is a posterior, slow pathway.", "contents": "Physiology of \"atypical\" atrioventricular junctional reentrant tachycardia occurring following radiofrequency catheter modification of the atrioventricular node. The physiology of atypical atrioventricular junctional reentrant tachycardia (AVJRT) occurring following catheter modification of the AV node is poorly defined. Six patients undergoing radiofrequency current catheter modification of the AV node had inducible atypical AVJRT before or after AV nodal modification. Typical AVJRT was differentiated from atypical AVJRT by a ventriculoatrial (VA) time < 60 msec in the His-bundle electrogram recording. Five of six patients had typical AVJRT and two had atypical AVJRT prior to AV nodal modification. Following anterior approach AV nodal modification, previously undetected atypical AVJRT was induced in four patients. Earliest retrograde atrial activation in the posterior septum was documented in all patients with atypical AVJRT prior to modification and in three of four patients with atypical AVJRT following modification. The AH intervals during tachycardia were 320 +/- 52 msec in typical AVJRT, 88 +/- 33 msec in the premodification atypical AVJRTs, and 172 +/- 12 msec in the postmodification atypical AVJRTs (P = 0.0001). The AH/HA ratios were 4.1 +/- 0.9 in typical AVJRT, 0.5 +/- 0.2 in the premodification atypical AVJRTs, and 0.9 +/- 0.2 in the postmodification atypical AVJRTs (P = 0.0001). Two patients with postmodification atypical AVJRT underwent further posterior approach AV node modification that resulted in VA block. One patient with postmodification atypical AVJRT had further anterior approach AV nodal modification that resulted in heart block. The retrograde limb of the atypical AVJRT seen following anterior approach AV nodal modification is a posterior, slow pathway."} {"id": "PMID:1282250", "title": "Detecting right ventricular volume changes using the conductance catheter.", "content": "The purpose of this study was to assess the role of conductance catheter position within the right ventricle in obtaining adequate indications of phasic changes in ventricular volume. Possible applications of this technology are in rate responsive pacemakers and implantable defibrilators. The conductance catheter was placed in the right ventricle by cannulation of a jugular or femoral vein or a branch of the pulmonary artery. Position within the ventricle was documented from biplane fluoroscopy. Stroke volume was perturbed by: bolus injection of blood, vagal stimulation, venous infusion of methylcholine chloride, or isoprenaline. Four criteria were used to assess the quality of volume signals: (1) volume signal phase relative to the electrocardiogram; (2) magnitude parity of volume change from each electrode pair; (3) freedom from artifact; and (4) indication of stroke volume change during interventions. Greyhound dogs of either sex (n = 33), weight 20-32 kg. A total of 236 recordings from 14 distinct catheter positions were analyzed. Catheter positions originating from a femoral cannulation and one position from the pulmonary artery gave markedly superior volume transduction compared to those from the jugular route. Although right ventricular volume transduction was possible from all catheter trajectories, those resulting from the femoral approach were clearly superior. In the right ventricle, the inability to transduce a sufficient proportion of ventricular volume, in concert with the potential sensitivity of the catheter to atrial volume changes, may seriously limit the potential of the conductance technique in the applications envisaged.", "contents": "Detecting right ventricular volume changes using the conductance catheter. The purpose of this study was to assess the role of conductance catheter position within the right ventricle in obtaining adequate indications of phasic changes in ventricular volume. Possible applications of this technology are in rate responsive pacemakers and implantable defibrilators. The conductance catheter was placed in the right ventricle by cannulation of a jugular or femoral vein or a branch of the pulmonary artery. Position within the ventricle was documented from biplane fluoroscopy. Stroke volume was perturbed by: bolus injection of blood, vagal stimulation, venous infusion of methylcholine chloride, or isoprenaline. Four criteria were used to assess the quality of volume signals: (1) volume signal phase relative to the electrocardiogram; (2) magnitude parity of volume change from each electrode pair; (3) freedom from artifact; and (4) indication of stroke volume change during interventions. Greyhound dogs of either sex (n = 33), weight 20-32 kg. A total of 236 recordings from 14 distinct catheter positions were analyzed. Catheter positions originating from a femoral cannulation and one position from the pulmonary artery gave markedly superior volume transduction compared to those from the jugular route. Although right ventricular volume transduction was possible from all catheter trajectories, those resulting from the femoral approach were clearly superior. In the right ventricle, the inability to transduce a sufficient proportion of ventricular volume, in concert with the potential sensitivity of the catheter to atrial volume changes, may seriously limit the potential of the conductance technique in the applications envisaged."} {"id": "PMID:1282251", "title": "Observations on the epicardial activation of the normal human heart.", "content": "Serial hand mapping techniques in man have identified 3 to 5 sites of epicardial breaktrough (EBT). However, transmural epicardial excitation from the widely distributed His/Purkinje system suggests a more complicated pattern may exist. Multielectrode arrays used with large mapping systems during surgery often present complicated and sometimes inconsistent activation patterns. The purpose of this work is to reconcile epicardial activation in the normal human heart with anatomical and endocardial/intramural physiological recordings using multichannel computer mapping requiring only a single beat, and rigorously defined and applied activation time detection algorithms. Eighteen subjects undergoing surgery for Wolff-Parkinson-White syndrome were recorded with a 119 site sock array during nonpreexcited sinus rhythm. None had evidence of coronary artery disease and all exhibited a normal 12-lead ECG except during periods of preexcitation or tachycardia. Each was recorded bipolarly and four also were recorded monopolarly. Recordings revealed 8.0 +/- 1.6 EBTs (range 5 to 12). Closely spaced, multiple EBTs often were observed and usually confirmed using different activation time detection algorithms. The earliest EBT always occurred over the anterior right ventricle at 14.3 +/- 6.5 msec (range -1 to 29 msec) after QRS onset. Subsequent EBTs could occur at any ventricular site with variable latencies. In contrast to previous reports describing epicardial spread of activation from a few foci, a mosaic of epicardial activation emerges. These data are consistent with endocardially initiated transmural activation of the epicardium suggested by the anatomy of the His/Purkinje system and intramural recordings.", "contents": "Observations on the epicardial activation of the normal human heart. Serial hand mapping techniques in man have identified 3 to 5 sites of epicardial breaktrough (EBT). However, transmural epicardial excitation from the widely distributed His/Purkinje system suggests a more complicated pattern may exist. Multielectrode arrays used with large mapping systems during surgery often present complicated and sometimes inconsistent activation patterns. The purpose of this work is to reconcile epicardial activation in the normal human heart with anatomical and endocardial/intramural physiological recordings using multichannel computer mapping requiring only a single beat, and rigorously defined and applied activation time detection algorithms. Eighteen subjects undergoing surgery for Wolff-Parkinson-White syndrome were recorded with a 119 site sock array during nonpreexcited sinus rhythm. None had evidence of coronary artery disease and all exhibited a normal 12-lead ECG except during periods of preexcitation or tachycardia. Each was recorded bipolarly and four also were recorded monopolarly. Recordings revealed 8.0 +/- 1.6 EBTs (range 5 to 12). Closely spaced, multiple EBTs often were observed and usually confirmed using different activation time detection algorithms. The earliest EBT always occurred over the anterior right ventricle at 14.3 +/- 6.5 msec (range -1 to 29 msec) after QRS onset. Subsequent EBTs could occur at any ventricular site with variable latencies. In contrast to previous reports describing epicardial spread of activation from a few foci, a mosaic of epicardial activation emerges. These data are consistent with endocardially initiated transmural activation of the epicardium suggested by the anatomy of the His/Purkinje system and intramural recordings."} {"id": "PMID:1282252", "title": "Atrial flutter--update on the mechanism and treatment.", "content": "Atrial flutter is a common and usually benign but symptomatic supraventricular tachycardia. There is a striking similarity between patients with atrial flutter suggesting a common substrate despite the presence or absence of underlying heart disease. In man, the mechanism is a single reentrant circuit originating in the right atrium whose center appears to be functional within the anatomical constraints of the right atrium. The reentrant circuit of atrial flutter contains an area of slow conduction in the inferior right atrium but the size and exact location is uncertain. Drug therapy directed at terminating and preventing atrial flutter has been available for many years. The efficacy and safety of this therapy is not as well tested as is the same therapy for atrial fibrillation. The most effective way to terminate atrial flutter is a nonpharmacological approach. Several nonpharmacological methods provide new treatment options in the management of patients with drug resistant or hemodynamically unstable atrial flutter. The use of anticoagulation for this disorder is still evolving. There is a risk of clinically apparent thromboemboli in some patients with atrial flutter although the risk appears less than that for atrial fibrillation. In the future, refinements and improvements in therapy for atrial flutter will likely be derived from a better understanding of its mechanism.", "contents": "Atrial flutter--update on the mechanism and treatment. Atrial flutter is a common and usually benign but symptomatic supraventricular tachycardia. There is a striking similarity between patients with atrial flutter suggesting a common substrate despite the presence or absence of underlying heart disease. In man, the mechanism is a single reentrant circuit originating in the right atrium whose center appears to be functional within the anatomical constraints of the right atrium. The reentrant circuit of atrial flutter contains an area of slow conduction in the inferior right atrium but the size and exact location is uncertain. Drug therapy directed at terminating and preventing atrial flutter has been available for many years. The efficacy and safety of this therapy is not as well tested as is the same therapy for atrial fibrillation. The most effective way to terminate atrial flutter is a nonpharmacological approach. Several nonpharmacological methods provide new treatment options in the management of patients with drug resistant or hemodynamically unstable atrial flutter. The use of anticoagulation for this disorder is still evolving. There is a risk of clinically apparent thromboemboli in some patients with atrial flutter although the risk appears less than that for atrial fibrillation. In the future, refinements and improvements in therapy for atrial flutter will likely be derived from a better understanding of its mechanism."} {"id": "PMID:1282254", "title": "Postpausal ventricular fibrillation analyzed by Holter-ECG: a case report.", "content": "A 70-year-old male patient with a myocardial infarction, 3 months previously, happened to be wearing a Holter monitor at cardiac arrest during micturition. The patient had ventricular fibrillation (VF) and was successfully resuscitated by means of defibrillation. Analysis of the Holter tape revealed atrial fibrillation and secondary ventricular premature beats (VPB), i.e., VPBs dependent upon a relatively long interval between the two preceding heartbeats. The VF was preceded by an especially long R-R interval (1.45 sec) following a run of especially short R-R intervals implying the sharpest deceleration of the ventricular rate during 1 hour Holter recording preceding the cardiac arrest. A peculiar large alteration of the T wave configuration was also found to precede the VF.", "contents": "Postpausal ventricular fibrillation analyzed by Holter-ECG: a case report. A 70-year-old male patient with a myocardial infarction, 3 months previously, happened to be wearing a Holter monitor at cardiac arrest during micturition. The patient had ventricular fibrillation (VF) and was successfully resuscitated by means of defibrillation. Analysis of the Holter tape revealed atrial fibrillation and secondary ventricular premature beats (VPB), i.e., VPBs dependent upon a relatively long interval between the two preceding heartbeats. The VF was preceded by an especially long R-R interval (1.45 sec) following a run of especially short R-R intervals implying the sharpest deceleration of the ventricular rate during 1 hour Holter recording preceding the cardiac arrest. A peculiar large alteration of the T wave configuration was also found to precede the VF."} {"id": "PMID:1282255", "title": "NASPE Young Investigator Awardee 1992. Three-dimensional electrogram mapping improves ablation of left-sided accessory pathways.", "content": "Conventional electrogram mapping techniques for localization of accessory pathways during radiofrequency ablation procedures are time consuming and often inaccurate. We hypothesized that a computer generated, three-dimensional electrogram of retrograde atrial activation created from signal-averaged sequential endocardial bipolar electrograms (collected from the atrial aspect of the mitral annulus using a single transseptal catheter and then time aligned to a known myocardial activation reference) would improve left-sided accessory pathway atrial insertion site identification and increase ablation efficiency. Ablation efficiency was defined by procedure time, fluoroscopy time, duration of radiofrequency energy required to achieve initial accessory pathway block, cumulative ablation energy per procedure, and number of radiofrequency energy applications. Patients with single left-sided accessory atrioventricular connections were studied. Standard mapping results in 31 patients (group A) were compared to a three-dimensional electrogram approach used in 26 patients (group B). Three-dimensional electrogram mapping reduced procedure time (group A 3.8 +/- 1.6 vs group B 2.8 +/- 0.9 hours, P < 0.004), fluoroscopy time (group A 45.3 +/- 35.0 vs group B 25.1 +/- 10.5 min, P < 0.02), time to accessory pathway block (group A 2.6 +/- 1.5 vs group B 1.2 +/- 0.5 sec, P < 0.002), cumulative radiofrequency energy (group A 2126 +/- 2207 vs group B 636 +/- 586 joules, P < 0.0008), and radiofrequency energy applications (group A 5.0 +/- 4.4 vs group B 1.7 +/- 1.2, P < 0.0002). We conclude that three-dimensional electrogram mapping improves left-sided accessory pathway atrial insertion localization, reduces ablation procedure time and radiation exposure, and improves ablation efficiency.", "contents": "NASPE Young Investigator Awardee 1992. Three-dimensional electrogram mapping improves ablation of left-sided accessory pathways. Conventional electrogram mapping techniques for localization of accessory pathways during radiofrequency ablation procedures are time consuming and often inaccurate. We hypothesized that a computer generated, three-dimensional electrogram of retrograde atrial activation created from signal-averaged sequential endocardial bipolar electrograms (collected from the atrial aspect of the mitral annulus using a single transseptal catheter and then time aligned to a known myocardial activation reference) would improve left-sided accessory pathway atrial insertion site identification and increase ablation efficiency. Ablation efficiency was defined by procedure time, fluoroscopy time, duration of radiofrequency energy required to achieve initial accessory pathway block, cumulative ablation energy per procedure, and number of radiofrequency energy applications. Patients with single left-sided accessory atrioventricular connections were studied. Standard mapping results in 31 patients (group A) were compared to a three-dimensional electrogram approach used in 26 patients (group B). Three-dimensional electrogram mapping reduced procedure time (group A 3.8 +/- 1.6 vs group B 2.8 +/- 0.9 hours, P < 0.004), fluoroscopy time (group A 45.3 +/- 35.0 vs group B 25.1 +/- 10.5 min, P < 0.02), time to accessory pathway block (group A 2.6 +/- 1.5 vs group B 1.2 +/- 0.5 sec, P < 0.002), cumulative radiofrequency energy (group A 2126 +/- 2207 vs group B 636 +/- 586 joules, P < 0.0008), and radiofrequency energy applications (group A 5.0 +/- 4.4 vs group B 1.7 +/- 1.2, P < 0.0002). We conclude that three-dimensional electrogram mapping improves left-sided accessory pathway atrial insertion localization, reduces ablation procedure time and radiation exposure, and improves ablation efficiency."} {"id": "PMID:1282258", "title": "Effects of maternal smoking upon neuropsychological development in early childhood: importance of taking account of social and environmental factors.", "content": "Data from a prospective study of 548 children followed from birth to 4 years of age were analysed to determine whether maternal smoking during and/or after pregnancy affects children's neuropsychological development. The differences in mean developmental test scores between children whose mothers smoked and those of mothers who did not smoke were slight, with subscale scores only 2.4 to 4.1% lower in children whose mothers smoked. These differences were not statistically significant after adjustment for socio-economic status, quality of home environment and mother's intelligence, suggesting that the social and environmental factors are major confounders of the association of exposure to maternal smoking and neuropsychological development in childhood. In order to gain a better understanding of this area, more precise measures of exposure to environmental tobacco smoke and comprehensive consideration of confounders will be required.", "contents": "Effects of maternal smoking upon neuropsychological development in early childhood: importance of taking account of social and environmental factors. Data from a prospective study of 548 children followed from birth to 4 years of age were analysed to determine whether maternal smoking during and/or after pregnancy affects children's neuropsychological development. The differences in mean developmental test scores between children whose mothers smoked and those of mothers who did not smoke were slight, with subscale scores only 2.4 to 4.1% lower in children whose mothers smoked. These differences were not statistically significant after adjustment for socio-economic status, quality of home environment and mother's intelligence, suggesting that the social and environmental factors are major confounders of the association of exposure to maternal smoking and neuropsychological development in childhood. In order to gain a better understanding of this area, more precise measures of exposure to environmental tobacco smoke and comprehensive consideration of confounders will be required."} {"id": "PMID:1282260", "title": "Normal development of nerve-muscle synapses in mice lacking the prion protein gene.", "content": "The expression of acetylcholine receptors (AChR) at neuromuscular synapses in skeletal muscle is regulated by innervation. Recent evidence suggests that the neurotrophic factors involved in the expression of AChR subunit genes may be related to the prion protein (PrPc), a protein of unknown function expressed primarily in neurons which, in its modified form, PrPSc, is thought to have a role in the pathogenesis of transmissible spongiform encephalopathies. We have tested for an involvement of PrPc in the neurotrophic regulation of synaptic AChRs in muscle by comparing the contents of AChR epsilon- and gamma-subunit mRNAs by Northern blot analysis and by in situ hybridization in mice with normal and with deleted PrP genes. At the protein level, AChR expression was assessed electrophysiologically. No difference was found between muscles from the two types of animals, suggesting that the neural regulation of AChR subunit expression in skeletal muscle can be mediated by factors that are not derived from the PrP gene.", "contents": "Normal development of nerve-muscle synapses in mice lacking the prion protein gene. The expression of acetylcholine receptors (AChR) at neuromuscular synapses in skeletal muscle is regulated by innervation. Recent evidence suggests that the neurotrophic factors involved in the expression of AChR subunit genes may be related to the prion protein (PrPc), a protein of unknown function expressed primarily in neurons which, in its modified form, PrPSc, is thought to have a role in the pathogenesis of transmissible spongiform encephalopathies. We have tested for an involvement of PrPc in the neurotrophic regulation of synaptic AChRs in muscle by comparing the contents of AChR epsilon- and gamma-subunit mRNAs by Northern blot analysis and by in situ hybridization in mice with normal and with deleted PrP genes. At the protein level, AChR expression was assessed electrophysiologically. No difference was found between muscles from the two types of animals, suggesting that the neural regulation of AChR subunit expression in skeletal muscle can be mediated by factors that are not derived from the PrP gene."} {"id": "PMID:1282261", "title": "A patch-clamp study of GABA- and strychnine-sensitive glycine-activated currents in post-natal tissue-cultured hippocampal neurons.", "content": "GABA- and strychnine-sensitive glycine-activated currents in post-natal tissue-cultured hippocampal neurons were studied by using patch-clamp techniques. Current-voltage relations for both agonists in symmetrical Cl- solutions showed outward rectification. Strychnine-sensitive glycine-activated currents have not been studied in detail before in post-natal tissue-cultured hippocampal neurons. Partial desensitization of whole-cell currents was observed in symmetrical Cl- solutions during bath application of GABA- and glycine. In F-/Cl- solutions, both agonists gave a PF/Pcl value of about 0.06. The reversal potentials in mixtures of Cl- and SO4(2-) solutions were close to the equilibrium potentials of Cl- in the presence of both GABA and glycine. Single channels in inside-out excised patches with 2 mumol l-1 GABA and 5 mumol l-1 glycine in the pipette showed outward current rectification. The dose-response curves for GABA and glycine gave Kd values of 52 and 61 mumol l-1, respectively, and Hill coefficients close to 2. GABA and glycine binding were competitively blocked by their respective antagonists (bicuculline and strychnine). The similarities between GABA- and glycine-activated currents and the response in a combination of saturating concentrations of both GABA and glycine implied that the two agonists activated comparable numbers of anatomically distinct channels with very similar permeation properties.", "contents": "A patch-clamp study of GABA- and strychnine-sensitive glycine-activated currents in post-natal tissue-cultured hippocampal neurons. GABA- and strychnine-sensitive glycine-activated currents in post-natal tissue-cultured hippocampal neurons were studied by using patch-clamp techniques. Current-voltage relations for both agonists in symmetrical Cl- solutions showed outward rectification. Strychnine-sensitive glycine-activated currents have not been studied in detail before in post-natal tissue-cultured hippocampal neurons. Partial desensitization of whole-cell currents was observed in symmetrical Cl- solutions during bath application of GABA- and glycine. In F-/Cl- solutions, both agonists gave a PF/Pcl value of about 0.06. The reversal potentials in mixtures of Cl- and SO4(2-) solutions were close to the equilibrium potentials of Cl- in the presence of both GABA and glycine. Single channels in inside-out excised patches with 2 mumol l-1 GABA and 5 mumol l-1 glycine in the pipette showed outward current rectification. The dose-response curves for GABA and glycine gave Kd values of 52 and 61 mumol l-1, respectively, and Hill coefficients close to 2. GABA and glycine binding were competitively blocked by their respective antagonists (bicuculline and strychnine). The similarities between GABA- and glycine-activated currents and the response in a combination of saturating concentrations of both GABA and glycine implied that the two agonists activated comparable numbers of anatomically distinct channels with very similar permeation properties."} {"id": "PMID:1282262", "title": "Structural studies on the photoreceptor phytochrome: reevaluation of the epitope for monoclonal antibody Z-3B1.", "content": "The photoreceptor phytochrome is widely distributed in the plant kingdom from angiosperms to ferns, mosses and algae. The epitope for the monoclonal antibody Z-3B1 which exhibits wide-ranging cross-reactivity with phytochromes from higher and lower plants was mapped by the combination of several methods: by Western blot with proteolytic fragments of known localization, by sequence comparison of phytochromes from various plants, and by production of overlapping fusion proteins. The only sequence which is common to all positively-reacting fusion proteins is the sequence A-830 to R-859. This sequence must contain the Z-3B1 epitope. The best candidate is suggested to be the T-cell antigenic sequence K-Y-V/I-E-A/C-L-L-T (= K-848 to T-855). The significance of the highly conserved epitope in all phytochromes is discussed.", "contents": "Structural studies on the photoreceptor phytochrome: reevaluation of the epitope for monoclonal antibody Z-3B1. The photoreceptor phytochrome is widely distributed in the plant kingdom from angiosperms to ferns, mosses and algae. The epitope for the monoclonal antibody Z-3B1 which exhibits wide-ranging cross-reactivity with phytochromes from higher and lower plants was mapped by the combination of several methods: by Western blot with proteolytic fragments of known localization, by sequence comparison of phytochromes from various plants, and by production of overlapping fusion proteins. The only sequence which is common to all positively-reacting fusion proteins is the sequence A-830 to R-859. This sequence must contain the Z-3B1 epitope. The best candidate is suggested to be the T-cell antigenic sequence K-Y-V/I-E-A/C-L-L-T (= K-848 to T-855). The significance of the highly conserved epitope in all phytochromes is discussed."} {"id": "PMID:1282263", "title": "Production of monoclonal antibodies to human immunodeficiency virus type-2.", "content": "The ROD strain of the human immunodeficiency virus type 2 (HIV-2) was used to produce monoclonal antibodies. Virus grown in CEM cells was partially purified by ultracentrifugation and solubilized in a buffer containing Triton X-100. BALB/c mice were inoculated intraperitoneally with 50 micrograms of solubilized virus preparations mixed 1:1 with complete Freund's adjuvant. Animals were boosted on day 28 and sacrificed on day 31. Spleen cells from the immunized animals were fused with SP20/Ag 14 myeloma cells and cultured in HAT medium. Following selection of the hybrids of interest by an HIV-2 ELISA procedure, hybridomas were cloned twice by limiting dilution. Six clones were found to produce antibodies that reacted with HIV-2 antigens as judged by ELISA. These antibodies were concentrated by ammonium sulfate precipitation, and analyzed by the Western blot procedure. Monoclonal antibodies specifically reactive to an HIV protein of 68 KD were obtained. These antibodies did not react with an HIV-2 band of 55 KD. These data showed that the monoclonal antibodies recognized the carboxy terminal region (the RNAse H domain) of the HIV-2 retrotranscriptase enzyme.", "contents": "Production of monoclonal antibodies to human immunodeficiency virus type-2. The ROD strain of the human immunodeficiency virus type 2 (HIV-2) was used to produce monoclonal antibodies. Virus grown in CEM cells was partially purified by ultracentrifugation and solubilized in a buffer containing Triton X-100. BALB/c mice were inoculated intraperitoneally with 50 micrograms of solubilized virus preparations mixed 1:1 with complete Freund's adjuvant. Animals were boosted on day 28 and sacrificed on day 31. Spleen cells from the immunized animals were fused with SP20/Ag 14 myeloma cells and cultured in HAT medium. Following selection of the hybrids of interest by an HIV-2 ELISA procedure, hybridomas were cloned twice by limiting dilution. Six clones were found to produce antibodies that reacted with HIV-2 antigens as judged by ELISA. These antibodies were concentrated by ammonium sulfate precipitation, and analyzed by the Western blot procedure. Monoclonal antibodies specifically reactive to an HIV protein of 68 KD were obtained. These antibodies did not react with an HIV-2 band of 55 KD. These data showed that the monoclonal antibodies recognized the carboxy terminal region (the RNAse H domain) of the HIV-2 retrotranscriptase enzyme."} {"id": "PMID:1282264", "title": "[Interferon and its potential use in the treatment of infectious diseases].", "content": "Modern recombinant biotechnology has made possible the production of large amount of interferons and their use as immunotherapeutic agents. Most of the biological, physical and chemical characteristics of interferons has been established, including their classification, genetic structure, chemical composition and possible mechanisms of action. Interferons have been utilized in clinical studies with human and experimental animals against bacterial, mycotic, parasitic and viral infections. Success has been reported mainly when administered prophylactically against acute infections. Favorable results have been obtained, both prophylactic and therapeutically, in some chronic diseases and in those in which the microorganism has an intracellular phase during its life cycle. Moreover, a promising future has been suggested for the combined use of interferon with other antimicrobial drugs.", "contents": "[Interferon and its potential use in the treatment of infectious diseases]. Modern recombinant biotechnology has made possible the production of large amount of interferons and their use as immunotherapeutic agents. Most of the biological, physical and chemical characteristics of interferons has been established, including their classification, genetic structure, chemical composition and possible mechanisms of action. Interferons have been utilized in clinical studies with human and experimental animals against bacterial, mycotic, parasitic and viral infections. Success has been reported mainly when administered prophylactically against acute infections. Favorable results have been obtained, both prophylactic and therapeutically, in some chronic diseases and in those in which the microorganism has an intracellular phase during its life cycle. Moreover, a promising future has been suggested for the combined use of interferon with other antimicrobial drugs."} {"id": "PMID:1282265", "title": "Multiple pathways for repair of oxidative DNA damages caused by X rays and hydrogen peroxide in Escherichia coli.", "content": "The responses of Escherichia coli to X rays and hydrogen peroxide were examined in mutants which are deficient in one or more DNA repair genes. Mutant cells deficient in either exonuclease III (xthA) or endonuclease IV (nfo) had normal resistance to X rays, but an xthA-nfo double mutant showed a sensitivity increased over that of either parental strain. A DNA polymerase I mutant (polA) was more sensitive than the xthA-nfo mutant. Cells bearing mutations in all of the polA, xthA, and nfo genes were more sensitive to X rays than polA and xthA-nfo mutants. Similar repair responses were obtained by exposing these mutant cells to hydrogen peroxide, with the exception of the xthA mutant, which was hypersensitive to this agent. The DNA polymerase III mutant (polC(Ts)) was slightly more sensitive to the agents than the wild-type strain at the restrictive temperature. The sensitivity of the polC-xthA-nfo mutant to X rays and hydrogen peroxide was greater than that of polC but almost the same as that of the xthA-nfo mutant. From these results it appears that there are at least four repair pathways, the DNA polymerase I-, exonuclease III/endonuclease IV and DNA polymerase I-, exonuclease III/endonuclease IV and DNA polymerase III-, and exonuclease III/endonuclease IV-dependent pathways, for the repair of oxidative DNA damages in E. coli.", "contents": "Multiple pathways for repair of oxidative DNA damages caused by X rays and hydrogen peroxide in Escherichia coli. The responses of Escherichia coli to X rays and hydrogen peroxide were examined in mutants which are deficient in one or more DNA repair genes. Mutant cells deficient in either exonuclease III (xthA) or endonuclease IV (nfo) had normal resistance to X rays, but an xthA-nfo double mutant showed a sensitivity increased over that of either parental strain. A DNA polymerase I mutant (polA) was more sensitive than the xthA-nfo mutant. Cells bearing mutations in all of the polA, xthA, and nfo genes were more sensitive to X rays than polA and xthA-nfo mutants. Similar repair responses were obtained by exposing these mutant cells to hydrogen peroxide, with the exception of the xthA mutant, which was hypersensitive to this agent. The DNA polymerase III mutant (polC(Ts)) was slightly more sensitive to the agents than the wild-type strain at the restrictive temperature. The sensitivity of the polC-xthA-nfo mutant to X rays and hydrogen peroxide was greater than that of polC but almost the same as that of the xthA-nfo mutant. From these results it appears that there are at least four repair pathways, the DNA polymerase I-, exonuclease III/endonuclease IV and DNA polymerase I-, exonuclease III/endonuclease IV and DNA polymerase III-, and exonuclease III/endonuclease IV-dependent pathways, for the repair of oxidative DNA damages in E. coli."} {"id": "PMID:1282266", "title": "[Liatek HCV: the six-antigen test for confirmation of the presence of anti-HCV antibodies].", "content": "Fifty eight anti-HCV repeatable positive (the UBI HCV EIA, Microelisa test Organon Teknika) blood donors were tested using LIATEK-HCV EIA (Organon Teknika). The test was constructed using synthetic polypeptides renders possible to conduct separate investigation antibodies against structural and nonstructural antigens of HCV. In 51/58 (88 per cent) cases was agreement of the results with the UBI test, in 3/58 (5.1 per cent) results were negative, and in 4/58 (6.9 per cent) undetermined. In 90 per cent of the seropositive reactivity developed with four to six antigens. The most frequent \"serological pattern\" was anti: NS4, C1, C2, C3, C4 (31 per cent) and anti: NS4, NS5, C1, C2, C3, C4 (23.5 per cent).", "contents": "[Liatek HCV: the six-antigen test for confirmation of the presence of anti-HCV antibodies]. Fifty eight anti-HCV repeatable positive (the UBI HCV EIA, Microelisa test Organon Teknika) blood donors were tested using LIATEK-HCV EIA (Organon Teknika). The test was constructed using synthetic polypeptides renders possible to conduct separate investigation antibodies against structural and nonstructural antigens of HCV. In 51/58 (88 per cent) cases was agreement of the results with the UBI test, in 3/58 (5.1 per cent) results were negative, and in 4/58 (6.9 per cent) undetermined. In 90 per cent of the seropositive reactivity developed with four to six antigens. The most frequent \"serological pattern\" was anti: NS4, C1, C2, C3, C4 (31 per cent) and anti: NS4, NS5, C1, C2, C3, C4 (23.5 per cent)."} {"id": "PMID:1282267", "title": "Modulation of electrical activity in gastrointestinal smooth muscle by peptides.", "content": "A rise in intracellular calcium is the predominant signal that leads to the activation of the contractile machinery in gastrointestinal smooth muscle. The primary sources of activating calcium are illustrated in Fig. 2. Voltage- and peptide-mediated release of intracellular calcium contribute to activation of some gastrointestinal smooth muscles. However, the primary source of activating calcium appears to be an influx of calcium across the plasma membrane. The degree of modulation of electrical activity by peptides varies depending upon the region of the gastrointestinal tract studied. Second messenger systems are undoubtly involved in the transduction pathway for receptor-mediated changes in ion channel activity in gastrointestinal smooth muscle. However, in comparison to other excitable cell types, little is known about the coupling mechanisms whereby peptide-receptor binding alters ion channel activity in gastrointestinal smooth muscle. This represents one of the challenging areas to be studied in the field of gastrointestinal smooth muscle. One disease in which a better appreciation of the regulation of ion channel activity could lead to therapeutic benefit is irritable bowel syndrome. A coupling of smooth muscle electrical activity to hypermotility in irritable bowel syndrome has been reported. CCK increases the level of spike activity which triggers hypermotility [40]. It would follow that inhibition of calcium influx should reduce spiking and, therefore, hypermotility. In fact, the calcium channel blockers nifedipine and nicardipine have been shown to decrease colonic motility in irritable bowel syndrome patients [62-64]. As our understanding of gastrointestinal smooth muscle ion channels expands, development of a gastrointestinal selective calcium channel blocker may be possible. This class of agents would be effective in the treatment of irritable bowel syndrome and potentially other peptide-related spastic smooth muscle disorders.", "contents": "Modulation of electrical activity in gastrointestinal smooth muscle by peptides. A rise in intracellular calcium is the predominant signal that leads to the activation of the contractile machinery in gastrointestinal smooth muscle. The primary sources of activating calcium are illustrated in Fig. 2. Voltage- and peptide-mediated release of intracellular calcium contribute to activation of some gastrointestinal smooth muscles. However, the primary source of activating calcium appears to be an influx of calcium across the plasma membrane. The degree of modulation of electrical activity by peptides varies depending upon the region of the gastrointestinal tract studied. Second messenger systems are undoubtly involved in the transduction pathway for receptor-mediated changes in ion channel activity in gastrointestinal smooth muscle. However, in comparison to other excitable cell types, little is known about the coupling mechanisms whereby peptide-receptor binding alters ion channel activity in gastrointestinal smooth muscle. This represents one of the challenging areas to be studied in the field of gastrointestinal smooth muscle. One disease in which a better appreciation of the regulation of ion channel activity could lead to therapeutic benefit is irritable bowel syndrome. A coupling of smooth muscle electrical activity to hypermotility in irritable bowel syndrome has been reported. CCK increases the level of spike activity which triggers hypermotility [40]. It would follow that inhibition of calcium influx should reduce spiking and, therefore, hypermotility. In fact, the calcium channel blockers nifedipine and nicardipine have been shown to decrease colonic motility in irritable bowel syndrome patients [62-64]. As our understanding of gastrointestinal smooth muscle ion channels expands, development of a gastrointestinal selective calcium channel blocker may be possible. This class of agents would be effective in the treatment of irritable bowel syndrome and potentially other peptide-related spastic smooth muscle disorders."} {"id": "PMID:1282268", "title": "[Percutaneous alcoholization of a small hepatocarcinoma].", "content": "Twenty-nine small hepatocellular carcinomas (sHCCs) less than 5 cm in diameter were treated with percutaneous ethanol injection (PEI) under US guidance in 24 cirrhotic patients. The nodules were treated on an outpatient basis with 6-18 ethanol injections; the total amount of alcohol delivered to each lesion was 10-103 ml. Twenty-seven of the 29 HCCs (93.1%) showed no evidence viable neoplastic tissue at a dynamic CT scan combined with multiple fine-needle biopsies performed one month after the end of treatment; in 10 cases MR confirmed the presence of necrosis showing marked hypointensity of the lesions in T2-weighted images. None of the 27 necrotized sHCCs recurred locally during a 4-44 months' follow-up period (mean 18 months). Two lesions larger than 4 cm showed incomplete response to treatment. No complications occurred after a total number of 264 alcohol injections. The 1-year survival rate in the 16 patients with a follow-up longer than 12 months was 93.7%. PEI proved to be a safe and effective treatment for sHCCs. In particular, PEI can be viewed as a reliable alternative to surgery in the management of nodules less than 3 cm in diameter, considering the operative hazards and the high risk of new lesions occurring in resected livers.", "contents": "[Percutaneous alcoholization of a small hepatocarcinoma]. Twenty-nine small hepatocellular carcinomas (sHCCs) less than 5 cm in diameter were treated with percutaneous ethanol injection (PEI) under US guidance in 24 cirrhotic patients. The nodules were treated on an outpatient basis with 6-18 ethanol injections; the total amount of alcohol delivered to each lesion was 10-103 ml. Twenty-seven of the 29 HCCs (93.1%) showed no evidence viable neoplastic tissue at a dynamic CT scan combined with multiple fine-needle biopsies performed one month after the end of treatment; in 10 cases MR confirmed the presence of necrosis showing marked hypointensity of the lesions in T2-weighted images. None of the 27 necrotized sHCCs recurred locally during a 4-44 months' follow-up period (mean 18 months). Two lesions larger than 4 cm showed incomplete response to treatment. No complications occurred after a total number of 264 alcohol injections. The 1-year survival rate in the 16 patients with a follow-up longer than 12 months was 93.7%. PEI proved to be a safe and effective treatment for sHCCs. In particular, PEI can be viewed as a reliable alternative to surgery in the management of nodules less than 3 cm in diameter, considering the operative hazards and the high risk of new lesions occurring in resected livers."} {"id": "PMID:1282269", "title": "Cation regulation of guinea pig cardiac nitrobenzylthioinosine binding sites.", "content": "The effects of several ions on [3H]NBMPR specific binding were characterized in guinea pig cardiac membranes. Binding of [3H]NBMPR was enhanced by Mg2+ Ca2+, Na+ and K+ but inhibited by Mn2+, Cu2+ and Zn2+. The effects of Cu2+ and Zn2+ were observed in micromolar concentrations while the effects of the other cations were observed between 1 and 300 mM. The anions tested had no significant effect on the binding. Scatchard analyses of the [3H]NBMPR saturation equilibrium data showed that the enhancement by Na+ and Mg2+ was due to an increase in the number of binding sites number with no change in apparent affinity. The inhibition of the binding by Cu2+ and Zn2+ was due to a decrease in both the apparent affinity and the number of binding sites. The regulation by cations imply that [3H]NBMPR binding sites are physiological receptors that may be involved in postreceptor coupling.", "contents": "Cation regulation of guinea pig cardiac nitrobenzylthioinosine binding sites. The effects of several ions on [3H]NBMPR specific binding were characterized in guinea pig cardiac membranes. Binding of [3H]NBMPR was enhanced by Mg2+ Ca2+, Na+ and K+ but inhibited by Mn2+, Cu2+ and Zn2+. The effects of Cu2+ and Zn2+ were observed in micromolar concentrations while the effects of the other cations were observed between 1 and 300 mM. The anions tested had no significant effect on the binding. Scatchard analyses of the [3H]NBMPR saturation equilibrium data showed that the enhancement by Na+ and Mg2+ was due to an increase in the number of binding sites number with no change in apparent affinity. The inhibition of the binding by Cu2+ and Zn2+ was due to a decrease in both the apparent affinity and the number of binding sites. The regulation by cations imply that [3H]NBMPR binding sites are physiological receptors that may be involved in postreceptor coupling."} {"id": "PMID:1282270", "title": "Kappa agonist-induced reduction in dopamine release: site of action and tolerance.", "content": "Kappa opioid agonists are known to inhibit dopamine release. We sought to determine the site of this action and the relationship of tolerance to this effect. Microdialysis perfusion of the nucleus accumbens in unanesthetized rats was used to monitor dopamine release, as well as DOPAC, HVA, and 5-HIAA efflux. Administration of the kappa agonist U-50488H (0.5-10 mg/kg, s.c.) resulted in a dose-related inhibition of basal dopamine release and a delayed reduction in HVA efflux. When added directly to the perfusion medium, U-50488H (10 microM) similarly reduced dopamine release and HVA efflux; however, a much higher concentration (1 mM) produced a transient increase in dopamine release. The more potent kappa agonist, spiradoline mesylate (5 mg/kg, s.c.) caused a more profound and long lasting reduction in dopamine release than that observed with U-50488H. Repeated injections of spiradoline (7 injections over 3 days at 5 and 10 mg/kg, s.c.) resulted in a persistent reduction in dopamine release with no further reduction in release being observed following an acute injection of spiradoline (1 mg/kg, s.c.). We conclude that kappa agonists act to inhibit dopamine release from the nucleus accumbens via a direct effect in that region, and that tolerance does not occur to this neurochemical effect. Thus, kappa agonists may prove useful in chronic conditions resulting from excessive dopamine release.", "contents": "Kappa agonist-induced reduction in dopamine release: site of action and tolerance. Kappa opioid agonists are known to inhibit dopamine release. We sought to determine the site of this action and the relationship of tolerance to this effect. Microdialysis perfusion of the nucleus accumbens in unanesthetized rats was used to monitor dopamine release, as well as DOPAC, HVA, and 5-HIAA efflux. Administration of the kappa agonist U-50488H (0.5-10 mg/kg, s.c.) resulted in a dose-related inhibition of basal dopamine release and a delayed reduction in HVA efflux. When added directly to the perfusion medium, U-50488H (10 microM) similarly reduced dopamine release and HVA efflux; however, a much higher concentration (1 mM) produced a transient increase in dopamine release. The more potent kappa agonist, spiradoline mesylate (5 mg/kg, s.c.) caused a more profound and long lasting reduction in dopamine release than that observed with U-50488H. Repeated injections of spiradoline (7 injections over 3 days at 5 and 10 mg/kg, s.c.) resulted in a persistent reduction in dopamine release with no further reduction in release being observed following an acute injection of spiradoline (1 mg/kg, s.c.). We conclude that kappa agonists act to inhibit dopamine release from the nucleus accumbens via a direct effect in that region, and that tolerance does not occur to this neurochemical effect. Thus, kappa agonists may prove useful in chronic conditions resulting from excessive dopamine release."} {"id": "PMID:1282271", "title": "Blockade of electrical field stimulation-induced nonadrenergic noncholinergic (NANC) excitatory response of the guinea pig ileum.", "content": "Determination of guinea pig ileal response to electrical field stimulation (EFS) before and after complete adrenergic and cholinergic blockade showed that the nonadrenergic noncholinergic excitatory (NANC-e) response contributed 40% to the total contractile response. NANC-e responses were reproducible to consecutive identical EFS. Tetrodotoxin significantly blocked the NANC-e response. The NANC-e responses obtained before and after treatment of the tissues with receptor antagonists of histamine (pyrilamine), substance P ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP) and serotonin (5-HT1 & 5-HT2) indicated that the response could be blocked by substance P and serotonin antagonists. Only the serotonin antagonist cyproheptadine produced a dose-dependent blockade. Both substance P and serotonin are suggested to play an important role in the NANC-e neurotransmission.", "contents": "Blockade of electrical field stimulation-induced nonadrenergic noncholinergic (NANC) excitatory response of the guinea pig ileum. Determination of guinea pig ileal response to electrical field stimulation (EFS) before and after complete adrenergic and cholinergic blockade showed that the nonadrenergic noncholinergic excitatory (NANC-e) response contributed 40% to the total contractile response. NANC-e responses were reproducible to consecutive identical EFS. Tetrodotoxin significantly blocked the NANC-e response. The NANC-e responses obtained before and after treatment of the tissues with receptor antagonists of histamine (pyrilamine), substance P ([D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP) and serotonin (5-HT1 & 5-HT2) indicated that the response could be blocked by substance P and serotonin antagonists. Only the serotonin antagonist cyproheptadine produced a dose-dependent blockade. Both substance P and serotonin are suggested to play an important role in the NANC-e neurotransmission."} {"id": "PMID:1282276", "title": "Effects of aprotinin on heparin activities and heparin neutralization with protamine.", "content": "In order to investigate the new situation in which aprotinin is proposed as a novel approach to reducing post operative bleeding, specially in cardiopulmonary bypass (CPB) surgery during which heparin and protamine are commonly used, preliminary in vitro and in vivo studies have been performed. Aprotinin increases the anticoagulant heparin effects in vitro, and the hemorrhage time in vivo. But in addition to protamine, there are no statistically significant differences with heparin-protamine situation, indicating aprotinin does not disturb the neutralizing activities of protamine on heparin.", "contents": "Effects of aprotinin on heparin activities and heparin neutralization with protamine. In order to investigate the new situation in which aprotinin is proposed as a novel approach to reducing post operative bleeding, specially in cardiopulmonary bypass (CPB) surgery during which heparin and protamine are commonly used, preliminary in vitro and in vivo studies have been performed. Aprotinin increases the anticoagulant heparin effects in vitro, and the hemorrhage time in vivo. But in addition to protamine, there are no statistically significant differences with heparin-protamine situation, indicating aprotinin does not disturb the neutralizing activities of protamine on heparin."} {"id": "PMID:1282277", "title": "A case report of familial cyclic neutropenia.", "content": "A 34-year-old female with cyclic neutropenia is reported. Family studies showed that her three sons and her mother were also involved. Oscillations in the blood neutrophil counts were almost regular, with a periodicity of 21 days. Numbers of colony-forming unit--granulocyte macrophage (CFU-GM) formed from the bone marrow cells of normal volunteers co-cultured with the patient's serum or mononuclear cell-conditioned medium (MNC-CM) were examined. Her serum prepared during the neutropenic phase inhibited the growth of CFU-GM, while her MNC-CM stimulated it. Human granulocyte colony-stimulating factor (hG-CSF) level in her serum was persistently high, with the peak occurring during the neutropenic phase. These results suggest that some inhibitory factors in the serum may be pathophysiologically important for cyclic neutropenia. To control infections, a pharmacological dose of hG-CSF was administered for 7 days around the early neutropenic phase. Her peripheral neutrophil counts oscillated from 1,200/mm3 to 17,000/mm3 with G-CSF, and from 150/mm3 to 1,800/mm3 without G-CSF.", "contents": "A case report of familial cyclic neutropenia. A 34-year-old female with cyclic neutropenia is reported. Family studies showed that her three sons and her mother were also involved. Oscillations in the blood neutrophil counts were almost regular, with a periodicity of 21 days. Numbers of colony-forming unit--granulocyte macrophage (CFU-GM) formed from the bone marrow cells of normal volunteers co-cultured with the patient's serum or mononuclear cell-conditioned medium (MNC-CM) were examined. Her serum prepared during the neutropenic phase inhibited the growth of CFU-GM, while her MNC-CM stimulated it. Human granulocyte colony-stimulating factor (hG-CSF) level in her serum was persistently high, with the peak occurring during the neutropenic phase. These results suggest that some inhibitory factors in the serum may be pathophysiologically important for cyclic neutropenia. To control infections, a pharmacological dose of hG-CSF was administered for 7 days around the early neutropenic phase. Her peripheral neutrophil counts oscillated from 1,200/mm3 to 17,000/mm3 with G-CSF, and from 150/mm3 to 1,800/mm3 without G-CSF."} {"id": "PMID:1282280", "title": "[The fractionation of non-histone chromosomal proteins from rat kidney and liver and their DNA complexes by using the cation exchangers phosphocellulose and SE-Sephadex].", "content": "Results of the gradient chromatography of chromosomal nonhistone proteins of the rat liver and kidney and their complexes with DNA on the phosphocellulose and SE-Sephadex are presented. The profiles of elution of the preparation of the homologous tissues with NaCl linear gradient of 0.1-1.0 M are equal. In the fractions of 0.4-0.5 M NaCl, protein components are discovered only in the samples of kidney.", "contents": "[The fractionation of non-histone chromosomal proteins from rat kidney and liver and their DNA complexes by using the cation exchangers phosphocellulose and SE-Sephadex]. Results of the gradient chromatography of chromosomal nonhistone proteins of the rat liver and kidney and their complexes with DNA on the phosphocellulose and SE-Sephadex are presented. The profiles of elution of the preparation of the homologous tissues with NaCl linear gradient of 0.1-1.0 M are equal. In the fractions of 0.4-0.5 M NaCl, protein components are discovered only in the samples of kidney."} {"id": "PMID:1282282", "title": "Sequence determination and genetic content of an 8.9-kb restriction fragment in the short unique region and the internal inverted repeat of Marek's disease virus type 1 DNA.", "content": "The DNA sequence (8.9 kb) covering about 70% of the short unique region (Us) and part of the short inverted repeat of the Marek's disease virus type 1 GA strain was determined. Computer analysis of the sequence showed the presence of nine potential open reading frames (ORFs), consisting of more than 300 nucleotides in the Us region. Of these ORFs, four were found to be homologous to US10 (minor virion protein), US3 (protein kinase), US2, and US6 (gD) in the Us region of alpha-herpesvirus herpes simplex virus type 1. The protein kinase homologue is especially well conserved in alpha-herpesviruses. No counterpart of the nine MDV1 ORFs was found in the beta-herpes virus human cytomegalovirus and gamma-herpesvirus Epstein-Barr virus, suggesting that MDV1 is more similar to the alpha-herpesviruses. The junction of the Us region and the short inverted repeat was also determined by comparison between the sequences of the DNA fragments, including the terminal and internal repeats. Northern blot analysis showed that the Us region within the 8.9 kb sequence was transcriptionally active in MDV1-infected cells.", "contents": "Sequence determination and genetic content of an 8.9-kb restriction fragment in the short unique region and the internal inverted repeat of Marek's disease virus type 1 DNA. The DNA sequence (8.9 kb) covering about 70% of the short unique region (Us) and part of the short inverted repeat of the Marek's disease virus type 1 GA strain was determined. Computer analysis of the sequence showed the presence of nine potential open reading frames (ORFs), consisting of more than 300 nucleotides in the Us region. Of these ORFs, four were found to be homologous to US10 (minor virion protein), US3 (protein kinase), US2, and US6 (gD) in the Us region of alpha-herpesvirus herpes simplex virus type 1. The protein kinase homologue is especially well conserved in alpha-herpesviruses. No counterpart of the nine MDV1 ORFs was found in the beta-herpes virus human cytomegalovirus and gamma-herpesvirus Epstein-Barr virus, suggesting that MDV1 is more similar to the alpha-herpesviruses. The junction of the Us region and the short inverted repeat was also determined by comparison between the sequences of the DNA fragments, including the terminal and internal repeats. Northern blot analysis showed that the Us region within the 8.9 kb sequence was transcriptionally active in MDV1-infected cells."} {"id": "PMID:1282283", "title": "[The effect of insulin therapy on the level of natural killer cells of different immunological phenotypes (CD16+, CD56+ and CD57+) in the blood of patients with diabetes mellitus type I].", "content": "Flow cytometry with monoclonal antibody Leu-7 (CD57), Leu-11 (CD56) and Leu-19 (CD56) were used to study the content of different subpopulations of natural killer cells (NK-cells) in the blood of type I diabetes mellitus patients before and after insulin treatment and in healthy people. After a course of insulin therapy most patients showed restoration of the total cell number with antigens on their surface characteristic of NK-cells, especially CD56, that indicates the essential role of hypoinsulin in the depression of the NK-system. At the same time a small group of patients was distinguished who did not show such normalization. This may indicate participation of other mechanisms in the formation of natural immunity failure, in particular, the genetic.", "contents": "[The effect of insulin therapy on the level of natural killer cells of different immunological phenotypes (CD16+, CD56+ and CD57+) in the blood of patients with diabetes mellitus type I]. Flow cytometry with monoclonal antibody Leu-7 (CD57), Leu-11 (CD56) and Leu-19 (CD56) were used to study the content of different subpopulations of natural killer cells (NK-cells) in the blood of type I diabetes mellitus patients before and after insulin treatment and in healthy people. After a course of insulin therapy most patients showed restoration of the total cell number with antigens on their surface characteristic of NK-cells, especially CD56, that indicates the essential role of hypoinsulin in the depression of the NK-system. At the same time a small group of patients was distinguished who did not show such normalization. This may indicate participation of other mechanisms in the formation of natural immunity failure, in particular, the genetic."} {"id": "PMID:1282284", "title": "[Circulating immune complexes and immunoglobulins in patients with an acute macrofocal myocardial infarct].", "content": "One of the pathogenetic mechanisms of development of acute myocardial infarction are immunologic changes of the humoral type. Indices of circulating immune complexes and A. M. G. immunoglobulins in acute myocardial infarction indicate the extension of involvement of the cardiac muscle, development of severe complications for the diagnosis and prognosis of acute myocardial infarction. An unfavourable sign is significant reduction of the level of circulating immune complexes and immunoglobulins in acute myocardial infarction.", "contents": "[Circulating immune complexes and immunoglobulins in patients with an acute macrofocal myocardial infarct]. One of the pathogenetic mechanisms of development of acute myocardial infarction are immunologic changes of the humoral type. Indices of circulating immune complexes and A. M. G. immunoglobulins in acute myocardial infarction indicate the extension of involvement of the cardiac muscle, development of severe complications for the diagnosis and prognosis of acute myocardial infarction. An unfavourable sign is significant reduction of the level of circulating immune complexes and immunoglobulins in acute myocardial infarction."} {"id": "PMID:1282285", "title": "Future prospects for treatment of hemoglobinopathies.", "content": "Strategies for the treatment of sickle cell anemia and beta-thalassemia are founded on the knowledge that these disorders result from structural or functional defects in an adult gene for which an intact fetal counterpart exists. During the past decade, several pharmacologic agents have been investigated for their potential to ameliorate sickle cell anemia and beta-thalassemia by increasing the synthesis of fetal hemoglobin in adults. Progress in understanding globin gene regulation is now being combined with advances in retrovirus-mediated gene transfer, and the once-distant goal of providing gene therapy for hemoglobinopathies is rapidly approaching reality.", "contents": "Future prospects for treatment of hemoglobinopathies. Strategies for the treatment of sickle cell anemia and beta-thalassemia are founded on the knowledge that these disorders result from structural or functional defects in an adult gene for which an intact fetal counterpart exists. During the past decade, several pharmacologic agents have been investigated for their potential to ameliorate sickle cell anemia and beta-thalassemia by increasing the synthesis of fetal hemoglobin in adults. Progress in understanding globin gene regulation is now being combined with advances in retrovirus-mediated gene transfer, and the once-distant goal of providing gene therapy for hemoglobinopathies is rapidly approaching reality."} {"id": "PMID:1282286", "title": "[Peroxisomal neurologic diseases and Refsum disease: very long chain fatty acids and phytanic acid as diagnostic markers].", "content": "Peroxisomal disorders are genetic metabolic diseases with generalized, multiple, or single functional disturbances of the peroxisome. According to the extent of the functional disturbances 3 groups of diseases can be differentiated: disorders with generalized loss of peroxisomal functions (Zellweger syndrome, ZS; neonatal adrenoleukodystrophy, NALD; infantile Refsum's disease), disorders with multiple enzymatic defects (e.g. rhizomelic chondrodysplasia punctata), and disorders with a single enzymatic defect in the peroxisome, the most important being adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Adult Refsum's disease, a genetic neurological disorder with phytanic acid accumulation, is due to a mitochondrial enzyme deficiency, but is often considered together with peroxisomal diseases because of phytanic acid (PHYT) accumulation in most peroxisomal diseases. The main clinical and pathological criteria of the major disorders and the biochemical parameters of their differentiation are presented. Elevated levels of very long chain fatty acids (VLCFA) and/or PHYT are the primary diagnostic markers for all peroxisomal disorders and adult Refsum's disease, respectively. Our investigations disclosed 30 ALD/AMN hemizygotes, 16 ALD/AMN heterozygotes, 8 cases of ZS/NALD and 7 patients with adult Refsum's disease. In addition, 15 cases of peroxisomal disorders were confirmed by biochemical investigations in autopsy material. With regard to peroxisomal disorders, therapeutic concepts exist only for ALD/AMN: corticosteroid substitution for adrenal insufficiency, dietary treatment, and bone marrow transplantation (BMT). Adult Refsum's disease can be treated successfully by dietary therapy. In case of dietary treatment and BMT, assay of VLCFA and/or PHYT is important for the biochemical evaluation of these therapies.", "contents": "[Peroxisomal neurologic diseases and Refsum disease: very long chain fatty acids and phytanic acid as diagnostic markers]. Peroxisomal disorders are genetic metabolic diseases with generalized, multiple, or single functional disturbances of the peroxisome. According to the extent of the functional disturbances 3 groups of diseases can be differentiated: disorders with generalized loss of peroxisomal functions (Zellweger syndrome, ZS; neonatal adrenoleukodystrophy, NALD; infantile Refsum's disease), disorders with multiple enzymatic defects (e.g. rhizomelic chondrodysplasia punctata), and disorders with a single enzymatic defect in the peroxisome, the most important being adrenoleukodystrophy/adrenomyeloneuropathy (ALD/AMN). Adult Refsum's disease, a genetic neurological disorder with phytanic acid accumulation, is due to a mitochondrial enzyme deficiency, but is often considered together with peroxisomal diseases because of phytanic acid (PHYT) accumulation in most peroxisomal diseases. The main clinical and pathological criteria of the major disorders and the biochemical parameters of their differentiation are presented. Elevated levels of very long chain fatty acids (VLCFA) and/or PHYT are the primary diagnostic markers for all peroxisomal disorders and adult Refsum's disease, respectively. Our investigations disclosed 30 ALD/AMN hemizygotes, 16 ALD/AMN heterozygotes, 8 cases of ZS/NALD and 7 patients with adult Refsum's disease. In addition, 15 cases of peroxisomal disorders were confirmed by biochemical investigations in autopsy material. With regard to peroxisomal disorders, therapeutic concepts exist only for ALD/AMN: corticosteroid substitution for adrenal insufficiency, dietary treatment, and bone marrow transplantation (BMT). Adult Refsum's disease can be treated successfully by dietary therapy. In case of dietary treatment and BMT, assay of VLCFA and/or PHYT is important for the biochemical evaluation of these therapies."} {"id": "PMID:1282288", "title": "Management of severe atopic dermatitis.", "content": "The lack of knowledge concerning the pathophysiology of atopic dermatitis (AD) explains the absence of any specific treatment specially in severe atopic dermatitis. New treatments were recently suggested for the management of the disease. They all act on some component of the immune mechanisms which provoke the eczematous reactions. Among recent treatments proposed, I will discuss the use of cyclosporin A, puva therapy, thymopoietin and thymostimulin, antifungal therapy, alpha and gamma interferon, and treatment with interleukin 2.", "contents": "Management of severe atopic dermatitis. The lack of knowledge concerning the pathophysiology of atopic dermatitis (AD) explains the absence of any specific treatment specially in severe atopic dermatitis. New treatments were recently suggested for the management of the disease. They all act on some component of the immune mechanisms which provoke the eczematous reactions. Among recent treatments proposed, I will discuss the use of cyclosporin A, puva therapy, thymopoietin and thymostimulin, antifungal therapy, alpha and gamma interferon, and treatment with interleukin 2."} {"id": "PMID:1282289", "title": "Vasoactive intestinal polypeptide and substance P in the pathogenesis of atopic dermatitis.", "content": "Neurogenic components are probably involved in the pathogenesis of atopic dermatitis (AD) and several neuropeptides have been implicated in the mechanisms underlying this disease. The aim of the present study was to evaluate by radio-immunoassay (RIA), the vasoactive intestinal polypeptide (VIP) and substance P (SP) content in whole-skin homogenates of AD lesions. RIA was performed using an antiserum, AH78, recognizing the carboxy-terminal fragment VIP (22-28) and a polyclonal antiserum directed against SP. VIP levels were markedly increased in lesional AD skin (5.62 +/- 1.25 pmol/g tissue) vis-\u00e0-vis controls (0.43 +/- 0.08 pmol/g tissue), whereas SP levels were significantly lower in lesional skin (0.25 +/- 0.03 pmol/g tissue) than in normal skin (0.97 +/- 0.24 pmol/g tissue). The results confirm that VIP and SP are relevant to the pathogenesis of AD and their imbalance might reflect diverse roles of these NP in the modulation of AD lesion.", "contents": "Vasoactive intestinal polypeptide and substance P in the pathogenesis of atopic dermatitis. Neurogenic components are probably involved in the pathogenesis of atopic dermatitis (AD) and several neuropeptides have been implicated in the mechanisms underlying this disease. The aim of the present study was to evaluate by radio-immunoassay (RIA), the vasoactive intestinal polypeptide (VIP) and substance P (SP) content in whole-skin homogenates of AD lesions. RIA was performed using an antiserum, AH78, recognizing the carboxy-terminal fragment VIP (22-28) and a polyclonal antiserum directed against SP. VIP levels were markedly increased in lesional AD skin (5.62 +/- 1.25 pmol/g tissue) vis-\u00e0-vis controls (0.43 +/- 0.08 pmol/g tissue), whereas SP levels were significantly lower in lesional skin (0.25 +/- 0.03 pmol/g tissue) than in normal skin (0.97 +/- 0.24 pmol/g tissue). The results confirm that VIP and SP are relevant to the pathogenesis of AD and their imbalance might reflect diverse roles of these NP in the modulation of AD lesion."} {"id": "PMID:1282287", "title": "[Pain reduction by trans-articular atlanto-axial screw fixation in patients with chronic polyarthritis].", "content": "To reduce the risk of cervical myelopathy, 32 patients suffering from rheumatoid arthritis (RA) and atlanto-axial dislocation (AAD) underwent a suboccipital fusion. All patients were interviewed with a pain questionnaire after a mean postoperative follow-up of 21 months (range 2-46). The results indicate a significant postoperative pain reduction as assessed by a visual numeric analogue scale, as well as a reduction of analgesic consumption.", "contents": "[Pain reduction by trans-articular atlanto-axial screw fixation in patients with chronic polyarthritis]. To reduce the risk of cervical myelopathy, 32 patients suffering from rheumatoid arthritis (RA) and atlanto-axial dislocation (AAD) underwent a suboccipital fusion. All patients were interviewed with a pain questionnaire after a mean postoperative follow-up of 21 months (range 2-46). The results indicate a significant postoperative pain reduction as assessed by a visual numeric analogue scale, as well as a reduction of analgesic consumption."} {"id": "PMID:1282290", "title": "Abnormal cutaneous neurosensitivity in atopic skin.", "content": "Having found an inability of patients with atopic eczema to distinguish different levels of iontophoretically applied histamine concentrations, as shown by their diminished vascular reactions and itch responses, and reviewing this result in the light of our new findings of smaller flare reactions and weaker itch sensations following different concentrations of intradermally injected substance P, we have concluded that unmyelinated afferent skin nerve fibres in these patients seem to be affected by the pathophysiological mechanism of atopic eczema. We therefore suspect that a down-regulation of histamine receptors at nerve endings compensates for elevated histamine release from cutaneous mast cells in patients with atopic eczema.", "contents": "Abnormal cutaneous neurosensitivity in atopic skin. Having found an inability of patients with atopic eczema to distinguish different levels of iontophoretically applied histamine concentrations, as shown by their diminished vascular reactions and itch responses, and reviewing this result in the light of our new findings of smaller flare reactions and weaker itch sensations following different concentrations of intradermally injected substance P, we have concluded that unmyelinated afferent skin nerve fibres in these patients seem to be affected by the pathophysiological mechanism of atopic eczema. We therefore suspect that a down-regulation of histamine receptors at nerve endings compensates for elevated histamine release from cutaneous mast cells in patients with atopic eczema."} {"id": "PMID:1282291", "title": "An alpha-fetoprotein-producing carcinoma of the rectum.", "content": "A rare alpha-fetoprotein (AFP)-producing carcinoma that originated in the rectum of a 54-year-old man is reported. High levels of AFP are found in the serum (5,126 ng/ml) and homogenate of the tumor tissue (2,600 ng/g). Two morphologic patterns were noted in the tumor. One was that of well differentiated tubular adenocarcinoma and the other was more polymorphous, in which the tumor cells grow in a solid-sheet with occasional glandular and papillary structures. Hyaline bodies and Schiller-Duval body-like structures were also found in the polymorphous area. There was a gradual transition between the well differentiated and the polymorphous area. AFP was positive in the polymorphous area and negative in the well differentiated area on immunohistochemical examination. These morphologic and immunohistochemical characteristics may suggest a differentiation toward embryonal carcinoma of the polymorphous component. Moreover, the polymorphous component showed marked vascular invasion and metastasis of liver as well as regional lymph nodes. AFP-producing carcinoma cells may be more aggressive than ordinary adenocarcinoma.", "contents": "An alpha-fetoprotein-producing carcinoma of the rectum. A rare alpha-fetoprotein (AFP)-producing carcinoma that originated in the rectum of a 54-year-old man is reported. High levels of AFP are found in the serum (5,126 ng/ml) and homogenate of the tumor tissue (2,600 ng/g). Two morphologic patterns were noted in the tumor. One was that of well differentiated tubular adenocarcinoma and the other was more polymorphous, in which the tumor cells grow in a solid-sheet with occasional glandular and papillary structures. Hyaline bodies and Schiller-Duval body-like structures were also found in the polymorphous area. There was a gradual transition between the well differentiated and the polymorphous area. AFP was positive in the polymorphous area and negative in the well differentiated area on immunohistochemical examination. These morphologic and immunohistochemical characteristics may suggest a differentiation toward embryonal carcinoma of the polymorphous component. Moreover, the polymorphous component showed marked vascular invasion and metastasis of liver as well as regional lymph nodes. AFP-producing carcinoma cells may be more aggressive than ordinary adenocarcinoma."} {"id": "PMID:1282293", "title": "[Laser photocoagulation of experimentally produced choroidal neovascularization. 2. Comparison of effects by dye and argon blue-green lasers].", "content": "Choroidal neovascularization was produced in 18 eyes of 12 rhesus monkeys by application of intense krypton laser photocoagulation. Eight weeks or later, a total of 34 choroidal neovascularizations were treated either by dye laser at wavelengths of 577 or 630 nm or by argon blue-green laser. The treated lesions were evaluated clinically and histopathologically from 24 hours to 3 months after treatment. All the treated lesions were apparently healed by each of the 3 laser modalities. Histopathologically, all the treated choroidal neovascularizations were occluded 24 hours after treatment. At 2 weeks to 3 months after treatment, newly-formed choroidal vessels were present in 3 of 9 lesions (33%) after 577 nm dye laser treatment, in 8 of 9 lesions (89%) after 630 nm dye laser treatment, and in 5 of 8 lesions (62%) after argon blue-green laser. These results seemed to show the clinical superiority of 577 nm dye laser in treating choroidal neovascularization.", "contents": "[Laser photocoagulation of experimentally produced choroidal neovascularization. 2. Comparison of effects by dye and argon blue-green lasers]. Choroidal neovascularization was produced in 18 eyes of 12 rhesus monkeys by application of intense krypton laser photocoagulation. Eight weeks or later, a total of 34 choroidal neovascularizations were treated either by dye laser at wavelengths of 577 or 630 nm or by argon blue-green laser. The treated lesions were evaluated clinically and histopathologically from 24 hours to 3 months after treatment. All the treated lesions were apparently healed by each of the 3 laser modalities. Histopathologically, all the treated choroidal neovascularizations were occluded 24 hours after treatment. At 2 weeks to 3 months after treatment, newly-formed choroidal vessels were present in 3 of 9 lesions (33%) after 577 nm dye laser treatment, in 8 of 9 lesions (89%) after 630 nm dye laser treatment, and in 5 of 8 lesions (62%) after argon blue-green laser. These results seemed to show the clinical superiority of 577 nm dye laser in treating choroidal neovascularization."} {"id": "PMID:1282292", "title": "Simple non-invasive mapping of pain pathways in living humans, and the effects of acute non-invasively induced pain on substance P, oncogen C-fos Ab1, oncogen C-fos Ab2, dopamine, and acetylcholine.", "content": "Most of the present knowledge on pain pathways is based on invasive animal experiments. In 1987, using the Bi-Digital O-Ring Test, Omura found that pain pathways can be evaluated non-invasively in living humans. In this paper, actual examples of such cases are reported. When mild pain was created by pinching different fingers of a normal human subject by placing a plastic clamp on the skin above a pain pathway, the indirect Bi-Digital O-Ring Test, through a fine electroconductive metal wire held by a third person, showed marked weakening of muscle tone of the third person resulting in the opening of the Bi-Digital O-Ring, which was preselected only when the minimum essential requirements to perform the Bi-Digital O-Ring Test were satisfied. The pain pathway thus detected had the following characteristics: For example, when the lateral side of the 5th finger of the left hand was pinched, the pathway was approximately along the ulnar nerve and then went to the dorsal root of the spinal cord around the area corresponding to the lower end of the 7th cervical vertebrae/upper end of the 1st thoracic vertebrae. At this level, the pain pathway goes to the opposite side (right side) then laterally up to the lower one-third of the medulla oblongata. It then turns horizontally from the right side to the left side at the same level, then goes up in the left side of the center of the medulla oblongata. At the left side it goes to the pons, and in the upper part of the pons it turns towards the midline. It then goes up and turns to the right side of the right cerebral cortex corresponding to the lateral side of the 5th finger.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Simple non-invasive mapping of pain pathways in living humans, and the effects of acute non-invasively induced pain on substance P, oncogen C-fos Ab1, oncogen C-fos Ab2, dopamine, and acetylcholine. Most of the present knowledge on pain pathways is based on invasive animal experiments. In 1987, using the Bi-Digital O-Ring Test, Omura found that pain pathways can be evaluated non-invasively in living humans. In this paper, actual examples of such cases are reported. When mild pain was created by pinching different fingers of a normal human subject by placing a plastic clamp on the skin above a pain pathway, the indirect Bi-Digital O-Ring Test, through a fine electroconductive metal wire held by a third person, showed marked weakening of muscle tone of the third person resulting in the opening of the Bi-Digital O-Ring, which was preselected only when the minimum essential requirements to perform the Bi-Digital O-Ring Test were satisfied. The pain pathway thus detected had the following characteristics: For example, when the lateral side of the 5th finger of the left hand was pinched, the pathway was approximately along the ulnar nerve and then went to the dorsal root of the spinal cord around the area corresponding to the lower end of the 7th cervical vertebrae/upper end of the 1st thoracic vertebrae. At this level, the pain pathway goes to the opposite side (right side) then laterally up to the lower one-third of the medulla oblongata. It then turns horizontally from the right side to the left side at the same level, then goes up in the left side of the center of the medulla oblongata. At the left side it goes to the pons, and in the upper part of the pons it turns towards the midline. It then goes up and turns to the right side of the right cerebral cortex corresponding to the lateral side of the 5th finger.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282294", "title": "Cytoprotective effects of prostaglandins and a new potent protease inhibitor in acute pancreatitis.", "content": "The redistribution of cathepsin B, a lysosomal enzyme, from the lysosomal pellet to the zymogen pellet in the subcellular fractionation, the colocalization of cathepsin B with digestive enzyme, and increased cellular, lysosomal, and mitochondrial fragility within acinar cells have been found during the early stages of caerulein-induced acute pancreatitis in rats. In the present study, the authors investigated the protective effects of prostaglandin E1 and E2, a combined therapy of these prostaglandins, and a new, synthetic, low molecular weight protease inhibitor, ONO3307, on the exocrine pancreas in this noninvasive model of experimental pancreatitis in vivo and in vitro. Prostaglandin E2, but not E1, prevented hyperamylasemia, congestion of amylase and trypsinogen in the acinar cells, redistribution of cathepsin B, and amylase and lactate dehydrogenase discharge from the dispersed acini. It also prevented cathepsin B leakage from the lysosomes and malate dehydrogenase leakage from the mitochondria in an almost dose-dependent manner, particularly at the dose of 100 micrograms/kg/hr continuous infusion. Furthermore, the combined therapy of prostaglandin E2 with ONO3307 strongly inhibited all the parameters tested in this study. This combination therapy seems to be the most effective against secretagogue-induced pancreatic injuries. These results indicate that cellular and subcellular organellar fragility seem to be closely involved in the pathogenesis of acute pancreatitis. Prostaglandin E2 seems to have important cytoprotective effects on the biologic membranes, such as a stabilizer of lysosomal or mitochondrial membranes. In addition, these findings also suggest the crucial roles of some unknown proteases in the etiology of acute pancreatitis, and indicate the clinical effectiveness of prostaglandins and this type of low molecular weight protease inhibitor for acute pancreatitis.", "contents": "Cytoprotective effects of prostaglandins and a new potent protease inhibitor in acute pancreatitis. The redistribution of cathepsin B, a lysosomal enzyme, from the lysosomal pellet to the zymogen pellet in the subcellular fractionation, the colocalization of cathepsin B with digestive enzyme, and increased cellular, lysosomal, and mitochondrial fragility within acinar cells have been found during the early stages of caerulein-induced acute pancreatitis in rats. In the present study, the authors investigated the protective effects of prostaglandin E1 and E2, a combined therapy of these prostaglandins, and a new, synthetic, low molecular weight protease inhibitor, ONO3307, on the exocrine pancreas in this noninvasive model of experimental pancreatitis in vivo and in vitro. Prostaglandin E2, but not E1, prevented hyperamylasemia, congestion of amylase and trypsinogen in the acinar cells, redistribution of cathepsin B, and amylase and lactate dehydrogenase discharge from the dispersed acini. It also prevented cathepsin B leakage from the lysosomes and malate dehydrogenase leakage from the mitochondria in an almost dose-dependent manner, particularly at the dose of 100 micrograms/kg/hr continuous infusion. Furthermore, the combined therapy of prostaglandin E2 with ONO3307 strongly inhibited all the parameters tested in this study. This combination therapy seems to be the most effective against secretagogue-induced pancreatic injuries. These results indicate that cellular and subcellular organellar fragility seem to be closely involved in the pathogenesis of acute pancreatitis. Prostaglandin E2 seems to have important cytoprotective effects on the biologic membranes, such as a stabilizer of lysosomal or mitochondrial membranes. In addition, these findings also suggest the crucial roles of some unknown proteases in the etiology of acute pancreatitis, and indicate the clinical effectiveness of prostaglandins and this type of low molecular weight protease inhibitor for acute pancreatitis."} {"id": "PMID:1282295", "title": "Signal transduction by T-cell receptors: mobilization of Ca and regulation of Ca-dependent effector molecules.", "content": "There have been major advances over the last several years in understanding the molecular basis of signaling by the T lymphocyte (T-cell) antigen receptor. In this article we discuss the early phases of T-cell activation with an emphasis on receptor-associated signaling molecules, mobilization of Ca, and on the possible roles of Ca in signal transduction. Ligation of the extracellular domains of the T-cell receptor activates receptor-associated tyrosine kinases that can phosphorylate the gamma-isoform of phospholipase C, increasing its catalytic activity. This leads to production of inositol 1,4,5-trisphosphate, release of stored intracellular Ca, and activation of Ca-permeable plasma membrane channels. Many of the critical T-cell signal transducing enzymes such as phospholipase C and protein kinase C contain intrinsic Ca-binding domains, but for the most part the rise in cytoplasmic Ca is transduced by specialized Ca-binding proteins that lack catalytic domains. The Ca-binding proteins found in T-cells include members of both the EF-hand and annexin families, as well as other types of Ca-binding proteins. In T-cells, a number of important kinases, phosphatases, and cytoskeleton-modulating enzymes are functionally Ca dependent but have no Ca-binding domains and therefore must sense changes in the cytoplasmic Ca level through interactions with Ca-binding proteins.", "contents": "Signal transduction by T-cell receptors: mobilization of Ca and regulation of Ca-dependent effector molecules. There have been major advances over the last several years in understanding the molecular basis of signaling by the T lymphocyte (T-cell) antigen receptor. In this article we discuss the early phases of T-cell activation with an emphasis on receptor-associated signaling molecules, mobilization of Ca, and on the possible roles of Ca in signal transduction. Ligation of the extracellular domains of the T-cell receptor activates receptor-associated tyrosine kinases that can phosphorylate the gamma-isoform of phospholipase C, increasing its catalytic activity. This leads to production of inositol 1,4,5-trisphosphate, release of stored intracellular Ca, and activation of Ca-permeable plasma membrane channels. Many of the critical T-cell signal transducing enzymes such as phospholipase C and protein kinase C contain intrinsic Ca-binding domains, but for the most part the rise in cytoplasmic Ca is transduced by specialized Ca-binding proteins that lack catalytic domains. The Ca-binding proteins found in T-cells include members of both the EF-hand and annexin families, as well as other types of Ca-binding proteins. In T-cells, a number of important kinases, phosphatases, and cytoskeleton-modulating enzymes are functionally Ca dependent but have no Ca-binding domains and therefore must sense changes in the cytoplasmic Ca level through interactions with Ca-binding proteins."} {"id": "PMID:1282296", "title": "Antisense oligonucleotides to CFTR confer a cystic fibrosis phenotype on B lymphocytes.", "content": "Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed at low levels in nonepithelial cells. Recently, we demonstrated that CFTR is responsible for cell cycle-dependent adenosine 3',5'-cyclic monophosphate-responsive Cl- permeability in lymphocytes. Agonist responsiveness of cystic fibrosis (CF) lymphocytes was restored by transfection with plasmid containing wild type CFTR cDNA. CFTR mRNA is expressed in the B lymphoid cell line GM03299; however, quantitative reverse transcriptase-polymerase chain reaction indicates that the level of CFTR mRNA is at least 1,000 times lower than in T84 cells. CFTR protein could not be detected by Western blot or by immunoprecipitation of in vitro phosphorylated protein. However, antisense oligonucleotides representing codons 1-12 of CFTR caused a complete inhibition of cell cycle-dependent Cl-permeability [as determined by 6-methoxy-N-(3-sulfopropyl)-quinolinium fluorescence digital-imaging microscopy], thereby inducing normal cells to acquire a \"CF phenotype.\" These studies provide direct evidence that a CFTR-associated Cl- permeability is present and measurable in lymphocytes, even though CFTR mRNA and protein are expressed at low levels.", "contents": "Antisense oligonucleotides to CFTR confer a cystic fibrosis phenotype on B lymphocytes. Cystic fibrosis transmembrane conductance regulator (CFTR) is expressed at low levels in nonepithelial cells. Recently, we demonstrated that CFTR is responsible for cell cycle-dependent adenosine 3',5'-cyclic monophosphate-responsive Cl- permeability in lymphocytes. Agonist responsiveness of cystic fibrosis (CF) lymphocytes was restored by transfection with plasmid containing wild type CFTR cDNA. CFTR mRNA is expressed in the B lymphoid cell line GM03299; however, quantitative reverse transcriptase-polymerase chain reaction indicates that the level of CFTR mRNA is at least 1,000 times lower than in T84 cells. CFTR protein could not be detected by Western blot or by immunoprecipitation of in vitro phosphorylated protein. However, antisense oligonucleotides representing codons 1-12 of CFTR caused a complete inhibition of cell cycle-dependent Cl-permeability [as determined by 6-methoxy-N-(3-sulfopropyl)-quinolinium fluorescence digital-imaging microscopy], thereby inducing normal cells to acquire a \"CF phenotype.\" These studies provide direct evidence that a CFTR-associated Cl- permeability is present and measurable in lymphocytes, even though CFTR mRNA and protein are expressed at low levels."} {"id": "PMID:1282297", "title": "Effects of okadaic acid indicate a role for dephosphorylation in pancreatic stimulus-secretion coupling.", "content": "Okadaic acid completely inhibits phosphatase 2A at nanomolar concentrations, while complete inhibition of type 1 phosphatases occurs at 1 microM. Phosphatase 2B is significantly inhibited only at concentrations > 1 microM. In rat pancreatic acini, 1 microM okadaic acid shifted the cholecystokinin (CCK) dose-response curve for stimulating amylase release to the right without reducing maximal secretion. At 3 microM, okadaic acid inhibited maximal CCK-induced amylase release to 78 +/- 7% of control, whereas the inactive analogue 1-Nor-okadaone had no effect. Three lines of evidence indicate that this inhibition by okadaic acid occurs at a late step in stimulus-secretion coupling: 1) intracellular Ca2+ signaling in response to agonist stimulation was not appreciably altered by okadaic acid; 2) stimulation with phorbol ester plus thapsigargin (thus by-passing receptor activation), which gave 85 +/- 4% of maximal CCK-induced amylase release, was inhibited 66 +/- 4% by 3 microM okadaic acid; and 3) Ca(2+)-induced amylase secretion in streptolysin O-permeabilized cells was also reduced by 85 +/- 7%. Two-dimensional polyacrylamide gel electrophoresis of 32P-labeled acini and autoradiography demonstrated that okadaic acid dose dependently increased overall protein phosphorylation. Correspondingly, okadaic acid also led to an inhibition of CCK-induced dephosphorylation. These results show that okadaic acid inhibits pancreatic acinar secretion at a step after generation of intracellular messengers and indicate a role for protein dephosphorylation in stimulus-secretion coupling.", "contents": "Effects of okadaic acid indicate a role for dephosphorylation in pancreatic stimulus-secretion coupling. Okadaic acid completely inhibits phosphatase 2A at nanomolar concentrations, while complete inhibition of type 1 phosphatases occurs at 1 microM. Phosphatase 2B is significantly inhibited only at concentrations > 1 microM. In rat pancreatic acini, 1 microM okadaic acid shifted the cholecystokinin (CCK) dose-response curve for stimulating amylase release to the right without reducing maximal secretion. At 3 microM, okadaic acid inhibited maximal CCK-induced amylase release to 78 +/- 7% of control, whereas the inactive analogue 1-Nor-okadaone had no effect. Three lines of evidence indicate that this inhibition by okadaic acid occurs at a late step in stimulus-secretion coupling: 1) intracellular Ca2+ signaling in response to agonist stimulation was not appreciably altered by okadaic acid; 2) stimulation with phorbol ester plus thapsigargin (thus by-passing receptor activation), which gave 85 +/- 4% of maximal CCK-induced amylase release, was inhibited 66 +/- 4% by 3 microM okadaic acid; and 3) Ca(2+)-induced amylase secretion in streptolysin O-permeabilized cells was also reduced by 85 +/- 7%. Two-dimensional polyacrylamide gel electrophoresis of 32P-labeled acini and autoradiography demonstrated that okadaic acid dose dependently increased overall protein phosphorylation. Correspondingly, okadaic acid also led to an inhibition of CCK-induced dephosphorylation. These results show that okadaic acid inhibits pancreatic acinar secretion at a step after generation of intracellular messengers and indicate a role for protein dephosphorylation in stimulus-secretion coupling."} {"id": "PMID:1282298", "title": "Anion channels for amino acids in MDCK cells.", "content": "Large losses of amino acids by diffusion were previously observed in Madin-Darby canine kidney (MDCK) cells during volume regulation. Also, an outward rectifying anion channel was activated. Because this channel was not selective among anions, it was suggested that it could be permeable to amino acids. Its permeability to aspartate, glutamate, and taurine was studied using the patch-clamp technique in the inside-out configuration. Solutions containing 500 mM aspartate or glutamate were used on the cytoplasmic side of excised patches to detect single-channel currents carried by these anions. Permeability ratios were estimated in two different ways: 1) from the shift in reversal potential of current-voltage curves after anion replacement in the bath solution and 2) from comparisons of amplitudes of single-channel currents carried by tested anions and chloride, respectively. The values of aspartate-to-chloride and glutamate-to-chloride permeability ratios obtained with both methods were quite consistent and were of the order of 0.2 for both amino acids. Taurine in solutions at physiological pH 7.3 is a zwitterionic molecule and bears no net charge. To detect single-channel currents carried by taurine, solutions containing 500 mM taurine at pH 8.2 were used in inside-out experiments. Under these conditions 120 mM of negatively charged taurine was present in the solutions bathing the cytoplasmic side of excised patches. The permeability ratio estimated from the shift in reversal potential was 0.75. These results showed that some of the organic compounds released by cells during regulatory volume decrease could diffuse through this outwardly rectifying anionic channel.", "contents": "Anion channels for amino acids in MDCK cells. Large losses of amino acids by diffusion were previously observed in Madin-Darby canine kidney (MDCK) cells during volume regulation. Also, an outward rectifying anion channel was activated. Because this channel was not selective among anions, it was suggested that it could be permeable to amino acids. Its permeability to aspartate, glutamate, and taurine was studied using the patch-clamp technique in the inside-out configuration. Solutions containing 500 mM aspartate or glutamate were used on the cytoplasmic side of excised patches to detect single-channel currents carried by these anions. Permeability ratios were estimated in two different ways: 1) from the shift in reversal potential of current-voltage curves after anion replacement in the bath solution and 2) from comparisons of amplitudes of single-channel currents carried by tested anions and chloride, respectively. The values of aspartate-to-chloride and glutamate-to-chloride permeability ratios obtained with both methods were quite consistent and were of the order of 0.2 for both amino acids. Taurine in solutions at physiological pH 7.3 is a zwitterionic molecule and bears no net charge. To detect single-channel currents carried by taurine, solutions containing 500 mM taurine at pH 8.2 were used in inside-out experiments. Under these conditions 120 mM of negatively charged taurine was present in the solutions bathing the cytoplasmic side of excised patches. The permeability ratio estimated from the shift in reversal potential was 0.75. These results showed that some of the organic compounds released by cells during regulatory volume decrease could diffuse through this outwardly rectifying anionic channel."} {"id": "PMID:1282299", "title": "Localization of the CHIP28 water channel in rat kidney.", "content": "CHIP28 is an integral membrane protein that has been identified as the erythrocyte water channel and that is also expressed in the kidney. Antibodies against erythrocyte CHIP28 were used to localize this protein along the rat urinary tubule. By Western blotting, CHIP28 was detected in kidney plasma membrane and endosome fractions. With the use of immunocytochemistry, CHIP28 was located in brush-border and basolateral plasma membranes of the proximal tubule. The initial S1 segment was weakly stained, but the S2 and S3 segments were heavily labeled. Subapical vesicles were also positive. Apical and basolateral membranes of the long thin descending limb were strongly labeled, but ascending thin and thick limbs of Henle and distal convoluted tubules were negative. Some vasa recta profiles in the medulla were positive. CHIP28 is, therefore, present in membranes with a high constitutive water permeability, where it probably acts as a transmembrane water-conducting channel. Finally, a weak staining of apical and basolateral membranes of cortical collecting duct principal cells was detectable, suggesting a potential relationship of CHIP28 to the vasopressin-sensitive water channel.", "contents": "Localization of the CHIP28 water channel in rat kidney. CHIP28 is an integral membrane protein that has been identified as the erythrocyte water channel and that is also expressed in the kidney. Antibodies against erythrocyte CHIP28 were used to localize this protein along the rat urinary tubule. By Western blotting, CHIP28 was detected in kidney plasma membrane and endosome fractions. With the use of immunocytochemistry, CHIP28 was located in brush-border and basolateral plasma membranes of the proximal tubule. The initial S1 segment was weakly stained, but the S2 and S3 segments were heavily labeled. Subapical vesicles were also positive. Apical and basolateral membranes of the long thin descending limb were strongly labeled, but ascending thin and thick limbs of Henle and distal convoluted tubules were negative. Some vasa recta profiles in the medulla were positive. CHIP28 is, therefore, present in membranes with a high constitutive water permeability, where it probably acts as a transmembrane water-conducting channel. Finally, a weak staining of apical and basolateral membranes of cortical collecting duct principal cells was detectable, suggesting a potential relationship of CHIP28 to the vasopressin-sensitive water channel."} {"id": "PMID:1282300", "title": "Ca2+ sensitivity of contractile activation during muscarinic stimulation of tracheal muscle.", "content": "The muscarinic agonists acetylcholine (ACh) and McN-A-343 act on a homogenous population of M3 receptors in canine tracheal smooth muscle; however, ACh is more effective at releasing stored Ca2+ and at stimulating inositol phosphate production. The effects of ACh and McN-A-343 on intracellular Ca2+ concentration ([Ca2+]i), myosin light chain (MLC) phosphorylation, active stress, and isotonic shortening velocity were compared to determine whether differences in their potency at stimulating second messenger pathways affected their ability to modulate the Ca2+ sensitivity of contractile filament activation. There were no differences in [Ca2+]i or isometric stress during the steady-state phase of submaximal contractions induced by ACh and McN-A-343. ACh produced slightly higher levels of MLC phosphorylation than McN-A-343; these levels were associated with much higher rates of isotonic shortening. This could indicate either an extremely high sensitivity of the shortening velocity to differences in MLC phosphorylation or that mechanisms other than MLC phosphorylation contribute to the regulation of shortening velocity. Results show that receptor-coupled pathways can modulate the relationship between [Ca2+]i and isotonic shortening velocity independently of the relationship between [Ca2+]i and isometric stress.", "contents": "Ca2+ sensitivity of contractile activation during muscarinic stimulation of tracheal muscle. The muscarinic agonists acetylcholine (ACh) and McN-A-343 act on a homogenous population of M3 receptors in canine tracheal smooth muscle; however, ACh is more effective at releasing stored Ca2+ and at stimulating inositol phosphate production. The effects of ACh and McN-A-343 on intracellular Ca2+ concentration ([Ca2+]i), myosin light chain (MLC) phosphorylation, active stress, and isotonic shortening velocity were compared to determine whether differences in their potency at stimulating second messenger pathways affected their ability to modulate the Ca2+ sensitivity of contractile filament activation. There were no differences in [Ca2+]i or isometric stress during the steady-state phase of submaximal contractions induced by ACh and McN-A-343. ACh produced slightly higher levels of MLC phosphorylation than McN-A-343; these levels were associated with much higher rates of isotonic shortening. This could indicate either an extremely high sensitivity of the shortening velocity to differences in MLC phosphorylation or that mechanisms other than MLC phosphorylation contribute to the regulation of shortening velocity. Results show that receptor-coupled pathways can modulate the relationship between [Ca2+]i and isotonic shortening velocity independently of the relationship between [Ca2+]i and isometric stress."} {"id": "PMID:1282301", "title": "Effects of insulin on total RNA, poly(A)+ RNA, and mRNA in primary cultures of rat hepatocytes.", "content": "The purpose of this study was to examine mechanisms involved in the regulation of protein synthesis in primary cultures of rat hepatocytes. Hepatocytes were maintained in a chemically defined serum-free medium in the presence or absence of insulin. The rate of protein synthesis in hepatocytes deprived of insulin between days 2 and 5 of culture was reduced to 67% of the rate observed in insulin-maintained controls. The decrease in protein synthetic rate was accompanied by a proportional fall in the content of both total RNA and poly(A)+RNA, suggesting that the capacity for protein synthesis was reduced in the absence of insulin. Both total RNA and poly(A)+ RNA contents and the protein synthetic rate were returned to control values after 3 days of insulin resupplementation. In addition, the effect of insulin on the expression of specific mRNAs was assessed by in vitro translation of total RNA followed by two-dimensional gel analysis of radiolabeled translation products. Only 13 of the greater than 150 spots discernible on the two-dimensional gels were altered in response to insulin. The mRNAs that were altered include examples of repression and stimulation of expression in response to insulin deprivation. Thus, in isolated rat hepatocytes, insulin regulates the capacity of both overall protein synthesis as well as the capacity for the synthesis of specific proteins.", "contents": "Effects of insulin on total RNA, poly(A)+ RNA, and mRNA in primary cultures of rat hepatocytes. The purpose of this study was to examine mechanisms involved in the regulation of protein synthesis in primary cultures of rat hepatocytes. Hepatocytes were maintained in a chemically defined serum-free medium in the presence or absence of insulin. The rate of protein synthesis in hepatocytes deprived of insulin between days 2 and 5 of culture was reduced to 67% of the rate observed in insulin-maintained controls. The decrease in protein synthetic rate was accompanied by a proportional fall in the content of both total RNA and poly(A)+RNA, suggesting that the capacity for protein synthesis was reduced in the absence of insulin. Both total RNA and poly(A)+ RNA contents and the protein synthetic rate were returned to control values after 3 days of insulin resupplementation. In addition, the effect of insulin on the expression of specific mRNAs was assessed by in vitro translation of total RNA followed by two-dimensional gel analysis of radiolabeled translation products. Only 13 of the greater than 150 spots discernible on the two-dimensional gels were altered in response to insulin. The mRNAs that were altered include examples of repression and stimulation of expression in response to insulin deprivation. Thus, in isolated rat hepatocytes, insulin regulates the capacity of both overall protein synthesis as well as the capacity for the synthesis of specific proteins."} {"id": "PMID:1282302", "title": "Effects of acute hypoxemia on insulin-like growth factors and their binding proteins in fetal sheep.", "content": "It has been proposed that insulin-like growth factor I (IGF-I) regulates fetal growth and differentiation. Plasma IGF-I concentrations correlate positively with fetal nutrient availability and newborn birth weights. To explore the hypothesis that hypoxemia decreases fetal growth by decreasing fetal IGF-I availability, we instrumented 14 fetal sheep with vascular catheters. At least 4 days after surgery, 10 fetuses were made acutely hypoxemic by infusing nitrogen into the maternal trachea for 3 h. Fetal blood oxyhemoglobin saturation decreased from 53 +/- 6 (SD) to 31 +/- 9%. Concomitantly, plasma IGF-I concentrations decreased from 91 +/- 11 to 67 +/- 10 ng/ml and IGF-I binding protein-1 concentration increased significantly, as assessed by ligand and Western blot analysis. Fetal IGF-I concentrations remained below control values throughout a subsequent recovery period (68 +/- 12 ng/ml at 6 h). In four control fetuses and in the ewes, plasma IGF-I concentrations were not significantly different from control values (97 +/- 18 and 181 +/- 18 ng/ml, respectively). These data support the hypothesis that decreases in fetal oxygen availability may decrease fetal growth by decreasing IGF-I production and availability.", "contents": "Effects of acute hypoxemia on insulin-like growth factors and their binding proteins in fetal sheep. It has been proposed that insulin-like growth factor I (IGF-I) regulates fetal growth and differentiation. Plasma IGF-I concentrations correlate positively with fetal nutrient availability and newborn birth weights. To explore the hypothesis that hypoxemia decreases fetal growth by decreasing fetal IGF-I availability, we instrumented 14 fetal sheep with vascular catheters. At least 4 days after surgery, 10 fetuses were made acutely hypoxemic by infusing nitrogen into the maternal trachea for 3 h. Fetal blood oxyhemoglobin saturation decreased from 53 +/- 6 (SD) to 31 +/- 9%. Concomitantly, plasma IGF-I concentrations decreased from 91 +/- 11 to 67 +/- 10 ng/ml and IGF-I binding protein-1 concentration increased significantly, as assessed by ligand and Western blot analysis. Fetal IGF-I concentrations remained below control values throughout a subsequent recovery period (68 +/- 12 ng/ml at 6 h). In four control fetuses and in the ewes, plasma IGF-I concentrations were not significantly different from control values (97 +/- 18 and 181 +/- 18 ng/ml, respectively). These data support the hypothesis that decreases in fetal oxygen availability may decrease fetal growth by decreasing IGF-I production and availability."} {"id": "PMID:1282303", "title": "Immunolocalization of antioxidant enzymes and isozymes of glutathione S-transferase in normal rat lung.", "content": "Polyclonal antisera to manganese and copper-zinc superoxide dismutases, catalase, glutathione peroxidase (GPx), and isozymes of glutathione S-transferase (liver and placental isolates, GST-L and GST-P, respectively) were used to localize these enzymes in normal rat lung by immunostaining. Light-microscopic results, using an immunoperoxidase technique, were expanded on by electron-microscopic immunogold localization. The findings were consistent with previous biochemical work. However, both GPx and GST-P were predominantly localized to extracellular connective tissue of the lung. These findings demonstrate the basal antioxidant enzyme phenotypes for parenchymal lung tissue at light- and electron-microscopic levels. Significant components of enzymatic defense to oxidant stress are heterogeneously distributed throughout rat lung tissue including both epithelial cell surfaces and the extracellular matrix.", "contents": "Immunolocalization of antioxidant enzymes and isozymes of glutathione S-transferase in normal rat lung. Polyclonal antisera to manganese and copper-zinc superoxide dismutases, catalase, glutathione peroxidase (GPx), and isozymes of glutathione S-transferase (liver and placental isolates, GST-L and GST-P, respectively) were used to localize these enzymes in normal rat lung by immunostaining. Light-microscopic results, using an immunoperoxidase technique, were expanded on by electron-microscopic immunogold localization. The findings were consistent with previous biochemical work. However, both GPx and GST-P were predominantly localized to extracellular connective tissue of the lung. These findings demonstrate the basal antioxidant enzyme phenotypes for parenchymal lung tissue at light- and electron-microscopic levels. Significant components of enzymatic defense to oxidant stress are heterogeneously distributed throughout rat lung tissue including both epithelial cell surfaces and the extracellular matrix."} {"id": "PMID:1282304", "title": "CFTR channels in immortalized human airway cells.", "content": "The cystic fibrosis (CF) gene codes for CF transmembrane regulator (CFTR), a small-conductance linear Cl- channel, but numerous studies have identified a larger conductance, rectifying Cl- channel as the adenosine 3',5'-cyclic monophosphate (cAMP)-regulated channel that is defective in airway cells. We examined Cl- conductance in a bronchial epithelial cell line that expresses CFTR, 16HBE14o-, (CFTR+) and in an airway cell line that does not, 9HTEo-/S, (CFTR-). Ionomycin or hypotonic Ringer increased iodide efflux from both cell lines; however, forskolin increased iodide efflux or whole cell Cl- currents only in CFTR+ cells. Forskolin-stimulated whole cell currents were linear, voltage independent, and blocked by iodide. Cell-attached and outside-out patches from confluent CFTR+ but not CFTR- cells revealed 6-pS channels having linear current-voltage relations, permselectivity Cl > I (partial block by external iodide), and little or no inhibition by 5-nitro-2-(3-phenylpropylamino)-benzoate. The number of active channels per patch increased from 0.6 to 3.0 after forskolin. Channels closed after excision with tau = 4 s, but activity could be prolonged with ATP or protein kinase A plus ATP. Channels were modeled with one open and four closed states and show apparent cooperativity in gating. Rectifying Cl- channels previously implicated in CF were not seen in cell-attached recordings from either cell line but were abundant in excised patches from both cell lines. Thus CFTR channels are the pathway for cAMP-mediated Cl- conductance in these human airway cells, Ca2+ and swelling-induced channels do not require CFTR, and CFTR-cells display a CF phenotype.", "contents": "CFTR channels in immortalized human airway cells. The cystic fibrosis (CF) gene codes for CF transmembrane regulator (CFTR), a small-conductance linear Cl- channel, but numerous studies have identified a larger conductance, rectifying Cl- channel as the adenosine 3',5'-cyclic monophosphate (cAMP)-regulated channel that is defective in airway cells. We examined Cl- conductance in a bronchial epithelial cell line that expresses CFTR, 16HBE14o-, (CFTR+) and in an airway cell line that does not, 9HTEo-/S, (CFTR-). Ionomycin or hypotonic Ringer increased iodide efflux from both cell lines; however, forskolin increased iodide efflux or whole cell Cl- currents only in CFTR+ cells. Forskolin-stimulated whole cell currents were linear, voltage independent, and blocked by iodide. Cell-attached and outside-out patches from confluent CFTR+ but not CFTR- cells revealed 6-pS channels having linear current-voltage relations, permselectivity Cl > I (partial block by external iodide), and little or no inhibition by 5-nitro-2-(3-phenylpropylamino)-benzoate. The number of active channels per patch increased from 0.6 to 3.0 after forskolin. Channels closed after excision with tau = 4 s, but activity could be prolonged with ATP or protein kinase A plus ATP. Channels were modeled with one open and four closed states and show apparent cooperativity in gating. Rectifying Cl- channels previously implicated in CF were not seen in cell-attached recordings from either cell line but were abundant in excised patches from both cell lines. Thus CFTR channels are the pathway for cAMP-mediated Cl- conductance in these human airway cells, Ca2+ and swelling-induced channels do not require CFTR, and CFTR-cells display a CF phenotype."} {"id": "PMID:1282305", "title": "[Cerebrovascular circulation in patients with oligomenorrhea].", "content": "Brain hemodynamics was studied in 76 patients with oligomenorrhea aged 18 to 35 from the data of rheoencephalography. Disorders of the regional tone of brain vessels were different and related to the time of the menstrual cycle disorder; this may be explained by the degree of changes in various neuromediator mechanisms of brain circulation and reproductive system function regulation.", "contents": "[Cerebrovascular circulation in patients with oligomenorrhea]. Brain hemodynamics was studied in 76 patients with oligomenorrhea aged 18 to 35 from the data of rheoencephalography. Disorders of the regional tone of brain vessels were different and related to the time of the menstrual cycle disorder; this may be explained by the degree of changes in various neuromediator mechanisms of brain circulation and reproductive system function regulation."} {"id": "PMID:1282307", "title": "A morphological study of the rabbit corneal assay.", "content": "We present a morphological study of the rabbit corneal assay. The effects of corneal pockets filled with methylcellulosis carriers with and without basic fibroblast growth factor (bFGF) were studied 4, 7, 11, 14 and 21 days following surgery. In the controls, strongly vacuolated keratocytes are present at the borders and especially at the bottom of the pocket. A large number of such cells can also be found in the region between the pocket and the epithelium. These cells obviously undergo necrosis. A few vacuolated keratocytes with poorly structured cytoplasm can even be found in the stroma between the pocket and the limbus. There are also changes in the epithelium. It is thinner than normal and the cells are longitudinally oriented. Construction of the pocket sometimes results in a fissure extending a variable distance from the bottom of the pocket to the limbus. Basic FGF induced blood-vessel growth from the limbus into the cornea. At least until day 7 this is accompanied by high vulnerability of the vessels, and changes in the pattern and structure of the extracellular matrix. Neutrophilic granulocytes, monocytes and a few mast cells migrate in front of the vessels. As in the controls, vacuolated and necrotic keratocytes are present within the stroma. From day 11 onward, many more vessels can be found in front of than behind the pocket, often located adjacent to vacuolated keratocytes. We suggest that an angiogenic substance placed in the corneal pocket is not the only angiogenic stimulus in the test, but acts together with many stimuli caused by the surgical manipulations.", "contents": "A morphological study of the rabbit corneal assay. We present a morphological study of the rabbit corneal assay. The effects of corneal pockets filled with methylcellulosis carriers with and without basic fibroblast growth factor (bFGF) were studied 4, 7, 11, 14 and 21 days following surgery. In the controls, strongly vacuolated keratocytes are present at the borders and especially at the bottom of the pocket. A large number of such cells can also be found in the region between the pocket and the epithelium. These cells obviously undergo necrosis. A few vacuolated keratocytes with poorly structured cytoplasm can even be found in the stroma between the pocket and the limbus. There are also changes in the epithelium. It is thinner than normal and the cells are longitudinally oriented. Construction of the pocket sometimes results in a fissure extending a variable distance from the bottom of the pocket to the limbus. Basic FGF induced blood-vessel growth from the limbus into the cornea. At least until day 7 this is accompanied by high vulnerability of the vessels, and changes in the pattern and structure of the extracellular matrix. Neutrophilic granulocytes, monocytes and a few mast cells migrate in front of the vessels. As in the controls, vacuolated and necrotic keratocytes are present within the stroma. From day 11 onward, many more vessels can be found in front of than behind the pocket, often located adjacent to vacuolated keratocytes. We suggest that an angiogenic substance placed in the corneal pocket is not the only angiogenic stimulus in the test, but acts together with many stimuli caused by the surgical manipulations."} {"id": "PMID:1282308", "title": "Distribution and possible origins of substance P-containing nerve fibers in the rat liver.", "content": "The distribution and possible origins of substance P-containing nerve fibers in the rat liver were investigated by immunohistochemistry and nerve transection. Nerve fibers with substance P-like immunoreactivity formed a more complex network than previously known in the walls of portal vein branches. Substance P-immunoreactive fibers were seen not only in and around the walls of the hepatic artery, but also in close association with the hepatic veins and bile ducts. Transection of the greater splanchnic nerves and/or the vagus nerves indicated that substance P-immunoreactive fibers in the walls of the portal and hepatic veins enter the liver via both nerves, and that those associated with the hepatic artery and bile ducts stem from the greater splanchnic nerves. The widespread distribution of hepatic substance P and its complex innervation pattern within the liver suggest that it is involved in a variety of physiological processes in this organ.", "contents": "Distribution and possible origins of substance P-containing nerve fibers in the rat liver. The distribution and possible origins of substance P-containing nerve fibers in the rat liver were investigated by immunohistochemistry and nerve transection. Nerve fibers with substance P-like immunoreactivity formed a more complex network than previously known in the walls of portal vein branches. Substance P-immunoreactive fibers were seen not only in and around the walls of the hepatic artery, but also in close association with the hepatic veins and bile ducts. Transection of the greater splanchnic nerves and/or the vagus nerves indicated that substance P-immunoreactive fibers in the walls of the portal and hepatic veins enter the liver via both nerves, and that those associated with the hepatic artery and bile ducts stem from the greater splanchnic nerves. The widespread distribution of hepatic substance P and its complex innervation pattern within the liver suggest that it is involved in a variety of physiological processes in this organ."} {"id": "PMID:1282309", "title": "[Pharmacology of low molecular weight hydroxyethyl starch].", "content": "In the last ten years, the practice of plasma volume expansion has changed significantly. Most clinicians have put a stop to the use of fresh frozen plasma because of growing concerns about hepatitis and AIDS transmission. Today, natural and synthetic colloids and crystalloids are used to a great extent. Although clinical practice varies from one institution to another, the most widely observed change was a major increase in the administration of human serum albumin (HSA). As a result, the cost of plasma volume expansion became so high that it justified finding safe and cheaper alternatives to HSA. Low molecular weight, hydroxyethylstarch (HES) are the synthetic colloids which are closest to HSA. HES are modified natural polymers whose physico-chemical properties are defined by their molecular weight and molar substitution ratio. Average molecular weights of these poly-dispersed solutions are approximately 200 to 250 kd (in weight) and 60 kd (in number). Hydroxyethylation, which slows down hydrolysis by alpha-amylase, is best quantified by the molar substitution ratio between the proportions of hydroxyethyl-ether and glucose. HES have pharmacokinetic properties which are independent of molecular weight and directly related to the molar substitution ratio. The two HES available in France are Elohes and Lomol, Elohes, at a concentration of 6%, has a colloid-osmotic effect close to that of plasma. It induces an initial plasma volume expansion greater than that of the infused volume, and has a long lasting effect (24 h) related to its molar substitution ratio (0.62). Lomol, at a concentration of 10%, is hyperoncotic.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Pharmacology of low molecular weight hydroxyethyl starch]. In the last ten years, the practice of plasma volume expansion has changed significantly. Most clinicians have put a stop to the use of fresh frozen plasma because of growing concerns about hepatitis and AIDS transmission. Today, natural and synthetic colloids and crystalloids are used to a great extent. Although clinical practice varies from one institution to another, the most widely observed change was a major increase in the administration of human serum albumin (HSA). As a result, the cost of plasma volume expansion became so high that it justified finding safe and cheaper alternatives to HSA. Low molecular weight, hydroxyethylstarch (HES) are the synthetic colloids which are closest to HSA. HES are modified natural polymers whose physico-chemical properties are defined by their molecular weight and molar substitution ratio. Average molecular weights of these poly-dispersed solutions are approximately 200 to 250 kd (in weight) and 60 kd (in number). Hydroxyethylation, which slows down hydrolysis by alpha-amylase, is best quantified by the molar substitution ratio between the proportions of hydroxyethyl-ether and glucose. HES have pharmacokinetic properties which are independent of molecular weight and directly related to the molar substitution ratio. The two HES available in France are Elohes and Lomol, Elohes, at a concentration of 6%, has a colloid-osmotic effect close to that of plasma. It induces an initial plasma volume expansion greater than that of the infused volume, and has a long lasting effect (24 h) related to its molar substitution ratio (0.62). Lomol, at a concentration of 10%, is hyperoncotic.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282310", "title": "Relationship between colloid osmotic pressure and plasma protein concentration in cattle, horses, dogs, and cats.", "content": "The relationship between colloid osmotic pressure (COP) and protein concentration was investigated for purified proteins and plasma samples obtained from cattle, horses, dogs, and cats. At equivalent concentrations, bovine albumin exerted a COP that exceeded that of gamma-globulins by a mean factor of 4.4. Similar relationships between COP and protein were observed in the other species. Consequently, for a given total protein concentration, COP was dependent on the albumin/gamma-globulins ratio. A commonly used nomogram for estimating COP from protein concentration, the Landis-Pappenheimer equation, did not provide reliable results for plasma samples from these species.", "contents": "Relationship between colloid osmotic pressure and plasma protein concentration in cattle, horses, dogs, and cats. The relationship between colloid osmotic pressure (COP) and protein concentration was investigated for purified proteins and plasma samples obtained from cattle, horses, dogs, and cats. At equivalent concentrations, bovine albumin exerted a COP that exceeded that of gamma-globulins by a mean factor of 4.4. Similar relationships between COP and protein were observed in the other species. Consequently, for a given total protein concentration, COP was dependent on the albumin/gamma-globulins ratio. A commonly used nomogram for estimating COP from protein concentration, the Landis-Pappenheimer equation, did not provide reliable results for plasma samples from these species."} {"id": "PMID:1282311", "title": "Measurement of HIV-1 reverse transcriptase by a nonradioactive assay system.", "content": "Reverse transcriptase activity was measured by incorporation of dUMP linked to digoxigenin into a suitable template-primer molecule. Incorporation was monitored by using peroxidase-conjugated Fab fragments directed against digoxigenin. The standard assay measuring incorporation of radiolabeled nucleotides into acid-precipitable material was compared with this new immunochemical assay with regard to its usefulness for testing inhibitors of reverse transcriptase.", "contents": "Measurement of HIV-1 reverse transcriptase by a nonradioactive assay system. Reverse transcriptase activity was measured by incorporation of dUMP linked to digoxigenin into a suitable template-primer molecule. Incorporation was monitored by using peroxidase-conjugated Fab fragments directed against digoxigenin. The standard assay measuring incorporation of radiolabeled nucleotides into acid-precipitable material was compared with this new immunochemical assay with regard to its usefulness for testing inhibitors of reverse transcriptase."} {"id": "PMID:1282312", "title": "Rapid and sensitive detection of Campylobacter spp. in chicken products by using the polymerase chain reaction.", "content": "The polymerase chain reaction (PCR) after a short enrichment culture was used to detect Campylobacter spp. in chicken products. After the 16S rRNA gene sequence of Campylobacter jejuni was determined and compared with known sequences from other enterobacteria, a primer and probe combination was selected from the region before V3 and the variable regions V3 and V5. With this primer set and probe, 426-bp fragments from C. jejuni, Campylobacter coli, and Campylobacter lari could be amplified. The detection limit of the PCR was 12.5 CFU. Chicken samples inoculated with 25 CFU of Campylobacter spp. per g were PCR positive after an 18-h enrichment, which resulted in 500 CFU/ml of culture broth. This PCR-culture assay was compared with the conventional method on naturally infected chicken products. Both methods detected the same number of positive and negative samples; however, the results of the PCR-culture assay were available within 48 h.", "contents": "Rapid and sensitive detection of Campylobacter spp. in chicken products by using the polymerase chain reaction. The polymerase chain reaction (PCR) after a short enrichment culture was used to detect Campylobacter spp. in chicken products. After the 16S rRNA gene sequence of Campylobacter jejuni was determined and compared with known sequences from other enterobacteria, a primer and probe combination was selected from the region before V3 and the variable regions V3 and V5. With this primer set and probe, 426-bp fragments from C. jejuni, Campylobacter coli, and Campylobacter lari could be amplified. The detection limit of the PCR was 12.5 CFU. Chicken samples inoculated with 25 CFU of Campylobacter spp. per g were PCR positive after an 18-h enrichment, which resulted in 500 CFU/ml of culture broth. This PCR-culture assay was compared with the conventional method on naturally infected chicken products. Both methods detected the same number of positive and negative samples; however, the results of the PCR-culture assay were available within 48 h."} {"id": "PMID:1282313", "title": "Uncultivated cyanobacteria, Chloroflexus-like inhabitants, and spirochete-like inhabitants of a hot spring microbial mat.", "content": "Analysis of 16S rRNA sequences retrieved as cDNA (16S rcDNA) from the Octopus Spring cyanobacterial mat has permitted phylogenetic characterization of some uncultivated community members, expanding our knowledge or diversity within this microbial community. Two new cyanobacterial 16S rRNA sequences were discovered, raising to four the number of cyanobacterial sequence types known to occur in the mat. None of the sequences found is that of the cultivated thermophilic cyanobacterium Synechococcus lividus. A new 16S rRNA sequence characteristic of green nonsulfur bacteria and their relatives was discovered, raising to two the number of such sequences known to exist in the mat. Both are unique among the 16S rRNA sequences of cultivated members of this group, including an Octopus Spring isolate of Chloroflexus aurantiacus and Heliothrix oregonensis, whose sequences we report herein. Two spirochete-like 16S rRNA sequences were discovered. One can be placed in the leptospira subdivision of the spirochete group, but the other has such a loose affiliation with the spirochete group that it might actually belong to an as yet unrecognized subdivision or even to a new eubacterial line of descent.", "contents": "Uncultivated cyanobacteria, Chloroflexus-like inhabitants, and spirochete-like inhabitants of a hot spring microbial mat. Analysis of 16S rRNA sequences retrieved as cDNA (16S rcDNA) from the Octopus Spring cyanobacterial mat has permitted phylogenetic characterization of some uncultivated community members, expanding our knowledge or diversity within this microbial community. Two new cyanobacterial 16S rRNA sequences were discovered, raising to four the number of cyanobacterial sequence types known to occur in the mat. None of the sequences found is that of the cultivated thermophilic cyanobacterium Synechococcus lividus. A new 16S rRNA sequence characteristic of green nonsulfur bacteria and their relatives was discovered, raising to two the number of such sequences known to exist in the mat. Both are unique among the 16S rRNA sequences of cultivated members of this group, including an Octopus Spring isolate of Chloroflexus aurantiacus and Heliothrix oregonensis, whose sequences we report herein. Two spirochete-like 16S rRNA sequences were discovered. One can be placed in the leptospira subdivision of the spirochete group, but the other has such a loose affiliation with the spirochete group that it might actually belong to an as yet unrecognized subdivision or even to a new eubacterial line of descent."} {"id": "PMID:1282314", "title": "Selection of a Pseudomonas cepacia strain constitutive for the degradation of trichloroethylene.", "content": "Tn5 insertion mutants of Pseudomonas cepacia G4 that were unable to degrade trichloroethylene (TCE), toluene, or phenol or to transform m-trifluoromethyl phenol (TFMP) to 7,7,7-trifluoro-2-hydroxy-6-oxo-2,4-heptadienoic acid (TFHA) were produced. Spontaneous reversion to growth on phenol or toluene as the sole source of carbon was observed in one mutant strain, G4 5223, at a frequency of approximately 1 x 10(-4) per generation. One such revertant, G4 5223-PR1, metabolized TFMP to TFHA and degraded TCE. Unlike wild-type G4, G4 5223-PR1 constitutively metabolized both TFMP and TCE without aromatic induction. G4 5223-PR1 also degraded cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, and 1,1-dichloroethylene and oxidized naphthalene to alpha naphthol constitutively. G4 5223-PR1 exhibited a slight retardation in growth rate at TCE concentrations of > or = 530 microM, whereas G4 (which was unable to metabolize TCE under the same noninducing growth conditions) remained unaffected. The constitutive degradative phenotype of G4 5223-PR1 was completely stable through 100 generations of nonselective growth.", "contents": "Selection of a Pseudomonas cepacia strain constitutive for the degradation of trichloroethylene. Tn5 insertion mutants of Pseudomonas cepacia G4 that were unable to degrade trichloroethylene (TCE), toluene, or phenol or to transform m-trifluoromethyl phenol (TFMP) to 7,7,7-trifluoro-2-hydroxy-6-oxo-2,4-heptadienoic acid (TFHA) were produced. Spontaneous reversion to growth on phenol or toluene as the sole source of carbon was observed in one mutant strain, G4 5223, at a frequency of approximately 1 x 10(-4) per generation. One such revertant, G4 5223-PR1, metabolized TFMP to TFHA and degraded TCE. Unlike wild-type G4, G4 5223-PR1 constitutively metabolized both TFMP and TCE without aromatic induction. G4 5223-PR1 also degraded cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, and 1,1-dichloroethylene and oxidized naphthalene to alpha naphthol constitutively. G4 5223-PR1 exhibited a slight retardation in growth rate at TCE concentrations of > or = 530 microM, whereas G4 (which was unable to metabolize TCE under the same noninducing growth conditions) remained unaffected. The constitutive degradative phenotype of G4 5223-PR1 was completely stable through 100 generations of nonselective growth."} {"id": "PMID:1282315", "title": "Species-specific oligonucleotide probes for five Bifidobacterium species detected in human intestinal microflora.", "content": "Portions of the 16S rRNA from closely related species of the genus Bifidobacterium that are found in the human intestinal microflora were sequenced in order to design species-specific oligonucleotide probes. Five oligonucleotide probes ranging from 16 to 19 bases in length and complementary to 16S rRNA sequences from Bifidobacterium adolescentis, B. bifidum, B. breve, B. infantis, and B. longum were synthesized. With crude high-molecular-weight RNA preparations as targets, these probes showed the desired species specificity, even down to a 1-nucleotide difference. For the practical evaluation of these probes, their specificity and sensitivity were tested against seven strains of the same species and 54 strains of heterologous bacteria with fixed whole cells as targets. The probes for B. adolescentis, B. breve, and B. longum showed efficient and specific hybridization. Although the probes for B. bifidum and B. infantis cross-reacted with a few bacterial strains not isolated from humans, these probes showed species specificity for human intestinal bacteria. These 16S rRNA probes should prove valuable for the identification and detection of human intestinal Bifidobacterium species.", "contents": "Species-specific oligonucleotide probes for five Bifidobacterium species detected in human intestinal microflora. Portions of the 16S rRNA from closely related species of the genus Bifidobacterium that are found in the human intestinal microflora were sequenced in order to design species-specific oligonucleotide probes. Five oligonucleotide probes ranging from 16 to 19 bases in length and complementary to 16S rRNA sequences from Bifidobacterium adolescentis, B. bifidum, B. breve, B. infantis, and B. longum were synthesized. With crude high-molecular-weight RNA preparations as targets, these probes showed the desired species specificity, even down to a 1-nucleotide difference. For the practical evaluation of these probes, their specificity and sensitivity were tested against seven strains of the same species and 54 strains of heterologous bacteria with fixed whole cells as targets. The probes for B. adolescentis, B. breve, and B. longum showed efficient and specific hybridization. Although the probes for B. bifidum and B. infantis cross-reacted with a few bacterial strains not isolated from humans, these probes showed species specificity for human intestinal bacteria. These 16S rRNA probes should prove valuable for the identification and detection of human intestinal Bifidobacterium species."} {"id": "PMID:1282316", "title": "[Target epitopes of monoclonal antibodies against ABH structures].", "content": "Comparing the reactivities of murine and human monoclonal antibodies directed against the antigens of A, B, and H blood groups by using different techniques (agglutination, inhibition by synthetic oligosaccharides and salivary antigens, tissue immunofluorescence, the use of an anti-idiotype antibody) enabled us to show a high heterogeneity of anti-A, anti-AB antibodies and, to some extend, anti-B and anti-H antibodies. Despite this diversity, the determination of the antibody specificity thanks to synthetic antigens made it possible to distinguish several groups of anti-A, B, AB, and H antibodies and to establish a classification that takes also their reactivity towards salivary and tissue antigens into account. On the contrary, few correlations were found between these tests and the ability of antibodies to agglutinate red blood cells of the different ABO-system variants.", "contents": "[Target epitopes of monoclonal antibodies against ABH structures]. Comparing the reactivities of murine and human monoclonal antibodies directed against the antigens of A, B, and H blood groups by using different techniques (agglutination, inhibition by synthetic oligosaccharides and salivary antigens, tissue immunofluorescence, the use of an anti-idiotype antibody) enabled us to show a high heterogeneity of anti-A, anti-AB antibodies and, to some extend, anti-B and anti-H antibodies. Despite this diversity, the determination of the antibody specificity thanks to synthetic antigens made it possible to distinguish several groups of anti-A, B, AB, and H antibodies and to establish a classification that takes also their reactivity towards salivary and tissue antigens into account. On the contrary, few correlations were found between these tests and the ability of antibodies to agglutinate red blood cells of the different ABO-system variants."} {"id": "PMID:1282317", "title": "Individual differences in basal cisternal cerebrospinal fluid 5-HIAA and HVA in monkeys. The effects of gender, age, physical characteristics, and matrilineal influences.", "content": "We examined the effects of gender, age, weight, length, body shape (ectomorphy), and matrilineal influences on cisternal cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) and homovanillic acid (HVA) in 78 socially living adult and adolescent vervet monkeys. CSF 5-HIAA and the 5-HIAA:HVA ratio were higher (by 27% and 18%, respectively) in females. In both sexes, CSF 5-HIAA and the 5-HIAA:HVA ratio increased with age. Neither weight nor length were independently related to CSF 5-HIAA or HVA; however, shape correlated with CSF 5-HIAA and HVA in males (higher in thin, long subjects). Male offspring had CSF 5-HIAA concentrations and 5-HIAA:HVA ratios that were significantly closer to their mothers than did age-matched, maternally unrelated males. Repeated measures of CSF 5-HIAA and HVA in another 22 males living in unvarying settings showed that individual differences in these measures persisted over time. The data underscore the impact of gender, age, and matrilineal relationships on individual differences in CSF monoamine metabolites and highlight the importance of controlling for age and gender in neuropharmacological investigations of clinical populations.", "contents": "Individual differences in basal cisternal cerebrospinal fluid 5-HIAA and HVA in monkeys. The effects of gender, age, physical characteristics, and matrilineal influences. We examined the effects of gender, age, weight, length, body shape (ectomorphy), and matrilineal influences on cisternal cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) and homovanillic acid (HVA) in 78 socially living adult and adolescent vervet monkeys. CSF 5-HIAA and the 5-HIAA:HVA ratio were higher (by 27% and 18%, respectively) in females. In both sexes, CSF 5-HIAA and the 5-HIAA:HVA ratio increased with age. Neither weight nor length were independently related to CSF 5-HIAA or HVA; however, shape correlated with CSF 5-HIAA and HVA in males (higher in thin, long subjects). Male offspring had CSF 5-HIAA concentrations and 5-HIAA:HVA ratios that were significantly closer to their mothers than did age-matched, maternally unrelated males. Repeated measures of CSF 5-HIAA and HVA in another 22 males living in unvarying settings showed that individual differences in these measures persisted over time. The data underscore the impact of gender, age, and matrilineal relationships on individual differences in CSF monoamine metabolites and highlight the importance of controlling for age and gender in neuropharmacological investigations of clinical populations."} {"id": "PMID:1282318", "title": "The lpr and gld genes in systemic autoimmunity: life and death in the Fas lane.", "content": "The single gene lpr and gld models of spontaneous systemic autoimmunity have attracted much attention in recent years. Here, Philip Cohen and Robert Eisenberg describe the fascinating recent findings that the lpr and gld [corrected] phenotypes result from defects in the Fas gene and, perhaps, in the ligand for fas, respectively.", "contents": "The lpr and gld genes in systemic autoimmunity: life and death in the Fas lane. The single gene lpr and gld models of spontaneous systemic autoimmunity have attracted much attention in recent years. Here, Philip Cohen and Robert Eisenberg describe the fascinating recent findings that the lpr and gld [corrected] phenotypes result from defects in the Fas gene and, perhaps, in the ligand for fas, respectively."} {"id": "PMID:1282319", "title": "CD40 and its ligand, an essential ligand-receptor pair for thymus-dependent B-cell activation.", "content": "The discovery of CD40 and its ligand, gp39, have created new perspectives on the activation of resting B cells by TH cells. Here, Randolph Noelle, Jeffrey Ledbetter and Alejandro Aruffo describe how these molecules were characterized and, from recent findings, examine their relevance to immune activation.", "contents": "CD40 and its ligand, an essential ligand-receptor pair for thymus-dependent B-cell activation. The discovery of CD40 and its ligand, gp39, have created new perspectives on the activation of resting B cells by TH cells. Here, Randolph Noelle, Jeffrey Ledbetter and Alejandro Aruffo describe how these molecules were characterized and, from recent findings, examine their relevance to immune activation."} {"id": "PMID:1282320", "title": "Detection of retinoic acid receptor mRNA in rat tissues by reverse transcriptase-polymerase chain reaction.", "content": "The presence of retinoic acid receptor (RAR) alpha, beta and gamma mRNA was examined in 16 different kinds of rat tissue using the highly sensitive reverse transcriptase-polymerase chain reaction technique. The data demonstrated that each tissue expressed at least two types of RAR mRNA. Among the three types of RAR mRNA, RAR alpha was widely expressed in all types of organ and was the dominant form expressed in the gastrointestinal tract. RAR beta mRNA was not present in the intestine and spleen. In addition, RAR beta mRNA levels were high in the heart, lung, brain, testis and epididymis. RAR gamma mRNA was abundant in both male and female reproductive systems, as well as epidermal tissues. The prevalence of each RAR mRNA in the tissues suggests the diverse biological roles of these receptors.", "contents": "Detection of retinoic acid receptor mRNA in rat tissues by reverse transcriptase-polymerase chain reaction. The presence of retinoic acid receptor (RAR) alpha, beta and gamma mRNA was examined in 16 different kinds of rat tissue using the highly sensitive reverse transcriptase-polymerase chain reaction technique. The data demonstrated that each tissue expressed at least two types of RAR mRNA. Among the three types of RAR mRNA, RAR alpha was widely expressed in all types of organ and was the dominant form expressed in the gastrointestinal tract. RAR beta mRNA was not present in the intestine and spleen. In addition, RAR beta mRNA levels were high in the heart, lung, brain, testis and epididymis. RAR gamma mRNA was abundant in both male and female reproductive systems, as well as epidermal tissues. The prevalence of each RAR mRNA in the tissues suggests the diverse biological roles of these receptors."} {"id": "PMID:1282321", "title": "Serum neopterin levels in patients with hepatocellular carcinoma.", "content": "Increased concentrations of neopterin have been found in conditions causing a stimulation of cellular immunity, including various malignancies. In liver diseases, serum or urinary neopterin levels have been studied in acute viral hepatitis, chronic hepatitis, fatty liver and liver cirrhosis. In the present study neopterin serum levels have been measured in 16 patients with hepatocellular carcinoma (HCC), in 32 patients with liver cirrhosis, and in 28 healthy subjects as controls. Mean values of serum neopterin were significantly increased (p < 0.01) in patients with HCC (15.89 +/- 6.34 nmol/l) when compared with those of normal subjects (4.74 +/- 2.13 nmol/l), but no difference was observed between patients with HCC (associated or not with liver cirrhosis) and patients with liver cirrhosis. Neopterin concentrations are not affected by liver cirrhosis aetiology, nor by its clinical severity, and are not correlated to the values of serum alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, and gamma-globulin. The results show that there is a consistent overlap of values in patients with HCC and liver cirrhosis; macrophage activation seems to be a feature of chronic liver diseases, irrespective of HCC development.", "contents": "Serum neopterin levels in patients with hepatocellular carcinoma. Increased concentrations of neopterin have been found in conditions causing a stimulation of cellular immunity, including various malignancies. In liver diseases, serum or urinary neopterin levels have been studied in acute viral hepatitis, chronic hepatitis, fatty liver and liver cirrhosis. In the present study neopterin serum levels have been measured in 16 patients with hepatocellular carcinoma (HCC), in 32 patients with liver cirrhosis, and in 28 healthy subjects as controls. Mean values of serum neopterin were significantly increased (p < 0.01) in patients with HCC (15.89 +/- 6.34 nmol/l) when compared with those of normal subjects (4.74 +/- 2.13 nmol/l), but no difference was observed between patients with HCC (associated or not with liver cirrhosis) and patients with liver cirrhosis. Neopterin concentrations are not affected by liver cirrhosis aetiology, nor by its clinical severity, and are not correlated to the values of serum alpha-fetoprotein, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl-transferase, and gamma-globulin. The results show that there is a consistent overlap of values in patients with HCC and liver cirrhosis; macrophage activation seems to be a feature of chronic liver diseases, irrespective of HCC development."} {"id": "PMID:1282322", "title": "The use of detergent-based aqueous two-phase systems for the isolation of extracellular proteins: purification of a lipase from Pseudomonas cepacia.", "content": "The partitioning of a variety of extracellular lipases, both pro- and eucaryotic, in detergent-based aqueous two-phase systems was examined. The results revealed that all procaryotic lipases showed a clear preference for the detergent-rich coacervate phase. In contrast, all eucaryotic lipases were significantly excluded from this phase, most probably caused by their glycosylation. The potential of such detergent-based systems for the isolation of extracellular lipases directly from cell-free culture broth was analyzed using the bacterium Pseudomonas cepacia (DSM 50181). This strain was identified after a limited screening for lipase activity. About 76% of the lipase could be extracted into the coacervate phase in just one purification step, leading to a four-fold concentration of lipase and a purification factor of 24.", "contents": "The use of detergent-based aqueous two-phase systems for the isolation of extracellular proteins: purification of a lipase from Pseudomonas cepacia. The partitioning of a variety of extracellular lipases, both pro- and eucaryotic, in detergent-based aqueous two-phase systems was examined. The results revealed that all procaryotic lipases showed a clear preference for the detergent-rich coacervate phase. In contrast, all eucaryotic lipases were significantly excluded from this phase, most probably caused by their glycosylation. The potential of such detergent-based systems for the isolation of extracellular lipases directly from cell-free culture broth was analyzed using the bacterium Pseudomonas cepacia (DSM 50181). This strain was identified after a limited screening for lipase activity. About 76% of the lipase could be extracted into the coacervate phase in just one purification step, leading to a four-fold concentration of lipase and a purification factor of 24."} {"id": "PMID:1282323", "title": "Entrapment of protein protease inhibitors in red blood cells.", "content": "Aprotinin and alpha 1-proteinase inhibitor have been encapsulated in human red blood cells (RBC) by a dialysis technique that involves transient hypotonic haemolysis followed by isotonic resealing. Both protease inhibitors can be encapsulated to a considerable extent. These molecules are released only by haemolysis of the cells and that excludes the possibility of using loaded erythrocytes for a slow release of the inhibitor(s) in the blood stream. However, the stability of the two inhibitors, the evidence for the binding of aprotinin to RBC components, and the results showing inhibition of endogenous proteolytic activity indicate that the inhibitors may be valuable in blocking, at least partially, undesired intraerythrocytic proteolytic reactions.", "contents": "Entrapment of protein protease inhibitors in red blood cells. Aprotinin and alpha 1-proteinase inhibitor have been encapsulated in human red blood cells (RBC) by a dialysis technique that involves transient hypotonic haemolysis followed by isotonic resealing. Both protease inhibitors can be encapsulated to a considerable extent. These molecules are released only by haemolysis of the cells and that excludes the possibility of using loaded erythrocytes for a slow release of the inhibitor(s) in the blood stream. However, the stability of the two inhibitors, the evidence for the binding of aprotinin to RBC components, and the results showing inhibition of endogenous proteolytic activity indicate that the inhibitors may be valuable in blocking, at least partially, undesired intraerythrocytic proteolytic reactions."} {"id": "PMID:1282326", "title": "Pretreatment natural killer antigen density correlates to clinical response in tumor patients receiving long-term subcutaneous recombinant interleukin-2 and recombinant interferon-alpha.", "content": "We evaluated density of the natural killer (NK) cell-associated CD56 antigen on circulating NK cells of 47 patients with advanced renal cell carcinoma. Patients received a combination of low-dose subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as home therapy. Antigen density of CD56 before therapy was 2.2-fold higher (P < 0.005) in patients who subsequently achieved a complete or partial remission when compared with patients who presented with progressive disease on therapy. After a 6-week treatment cycle, NK cells of treatment responders expressed significantly (2.1-fold; P < 0.005) more CD56 antigens than NK cells in nonresponding patients. These results suggested a potential role of both pre- and posttreatment NK antigen density levels as a biologic correlate to treatment response.", "contents": "Pretreatment natural killer antigen density correlates to clinical response in tumor patients receiving long-term subcutaneous recombinant interleukin-2 and recombinant interferon-alpha. We evaluated density of the natural killer (NK) cell-associated CD56 antigen on circulating NK cells of 47 patients with advanced renal cell carcinoma. Patients received a combination of low-dose subcutaneous recombinant interleukin-2 (rIL-2) and recombinant interferon-alpha (rIFN-alpha) as home therapy. Antigen density of CD56 before therapy was 2.2-fold higher (P < 0.005) in patients who subsequently achieved a complete or partial remission when compared with patients who presented with progressive disease on therapy. After a 6-week treatment cycle, NK cells of treatment responders expressed significantly (2.1-fold; P < 0.005) more CD56 antigens than NK cells in nonresponding patients. These results suggested a potential role of both pre- and posttreatment NK antigen density levels as a biologic correlate to treatment response."} {"id": "PMID:1282324", "title": "The basal forebrain cholinergic system in the raccoon.", "content": "The distribution of neurons displaying choline acetyltransferase (ChAT) immunoreactivity was examined in the raccoon basal forebrain using a rabbit antiserum and a monoclonal antibody. Alternating sections were used for Nissl staining. ChAT-positive neurons were arranged in a continuous mass extending from the medial septum to the caudal pole of the pallidum. Based upon spatial relations to fibre tracts, the clustering of neuronal groups, and cytological criteria, the basal forebrain magnocellular complex can be subdivided into several distinct regions. Although clear nuclear boundaries were often absent, the ChAT-positive neurons were divided into: the nucleus tractus diagonalis (comprising pars septi medialis, pars verticalis and pars horizontalis); nucleus praeopticus magnocellularis; substantia innominata; and the nucleus basalis of Meynert. Comparison with Nissl-stained sections indicated the presence of varying proportions of non-cholinergic neurons clustered or arranged loosely within these basal forebrain subdivisions. These data provide a structural basis for studies concerned with the topographical and physiological aspects of the raccoon basal forebrain cholinergic projections and its comparison with the basal forebrains of other species.", "contents": "The basal forebrain cholinergic system in the raccoon. The distribution of neurons displaying choline acetyltransferase (ChAT) immunoreactivity was examined in the raccoon basal forebrain using a rabbit antiserum and a monoclonal antibody. Alternating sections were used for Nissl staining. ChAT-positive neurons were arranged in a continuous mass extending from the medial septum to the caudal pole of the pallidum. Based upon spatial relations to fibre tracts, the clustering of neuronal groups, and cytological criteria, the basal forebrain magnocellular complex can be subdivided into several distinct regions. Although clear nuclear boundaries were often absent, the ChAT-positive neurons were divided into: the nucleus tractus diagonalis (comprising pars septi medialis, pars verticalis and pars horizontalis); nucleus praeopticus magnocellularis; substantia innominata; and the nucleus basalis of Meynert. Comparison with Nissl-stained sections indicated the presence of varying proportions of non-cholinergic neurons clustered or arranged loosely within these basal forebrain subdivisions. These data provide a structural basis for studies concerned with the topographical and physiological aspects of the raccoon basal forebrain cholinergic projections and its comparison with the basal forebrains of other species."} {"id": "PMID:1282325", "title": "The relationship of calbindin-containing neurons with substance P, Leu-enkephalin and cholecystokinin fibres: an immunohistochemical study in the rat thalamus.", "content": "In the rat thalamus, immunoreactivity for the calcium binding protein calbindin (Cb) is mostly confined to neuronal cell bodies, sometimes revealing proximal dendrites, of the midline, intralaminar and posterior regions. Substance P (SP)-, cholecystokinin (CCK)- and Leu-enkephalin (L-ENK)-immunoreactive (ir) elements in the thalamus are fibre-like structures, intermingled with punctate elements probably representing axonal arborizations and their synaptic boutons. These peptidergic fibres are unevenly distributed in several thalamic domains, including the areas that contain Cb-ir neurons. The relationship between Cb-ir cell bodies and these three different peptidergic systems of thalamic innervation was studied with immunohistochemistry. Single-labelling experiments on adjacent sections and double immunostaining on the same section were performed. A considerable overlap between Cb-ir perikarya and SP-ir fibres was found in most thalamic nuclei. In particular, in the intralaminar nuclei and posterior complex, SP-ir punctate elements were frequently observed in close proximity to Cb-ir cell bodies and dendrites. On the other hand, no consistent topographical correspondence between Cb-ir perikarya and CCK- or L-ENK-ir fibres was evident. Altogether, the present data suggest a selective anatomical and, possibly, functional relationship between SP and Cb in at least a subpopulation of rat thalamic neurons.", "contents": "The relationship of calbindin-containing neurons with substance P, Leu-enkephalin and cholecystokinin fibres: an immunohistochemical study in the rat thalamus. In the rat thalamus, immunoreactivity for the calcium binding protein calbindin (Cb) is mostly confined to neuronal cell bodies, sometimes revealing proximal dendrites, of the midline, intralaminar and posterior regions. Substance P (SP)-, cholecystokinin (CCK)- and Leu-enkephalin (L-ENK)-immunoreactive (ir) elements in the thalamus are fibre-like structures, intermingled with punctate elements probably representing axonal arborizations and their synaptic boutons. These peptidergic fibres are unevenly distributed in several thalamic domains, including the areas that contain Cb-ir neurons. The relationship between Cb-ir cell bodies and these three different peptidergic systems of thalamic innervation was studied with immunohistochemistry. Single-labelling experiments on adjacent sections and double immunostaining on the same section were performed. A considerable overlap between Cb-ir perikarya and SP-ir fibres was found in most thalamic nuclei. In particular, in the intralaminar nuclei and posterior complex, SP-ir punctate elements were frequently observed in close proximity to Cb-ir cell bodies and dendrites. On the other hand, no consistent topographical correspondence between Cb-ir perikarya and CCK- or L-ENK-ir fibres was evident. Altogether, the present data suggest a selective anatomical and, possibly, functional relationship between SP and Cb in at least a subpopulation of rat thalamic neurons."} {"id": "PMID:1282327", "title": "A paradigm for examining toxicant effects on viability, structure, and axonal transport of neurons in culture.", "content": "N1E.115 murine neuroblastoma cells differentiating in serum-free medium were used to develop a paradigm for testing neurotoxicity in vitro. The paradigm was designed to test the effects of toxicants on four different aspects of cell function or structure: 1. Viability as shown by the retention of cellular radiolabel (51Cr); 2. Growth and maintenance of neurites as reflected by the incidence and average length of these processes; 3. Gross structure of neurites; and 4. Velocity and flux of rapid anterograde and retrograde axonal transport as judged by video-enhanced differential interference contrast microscopy. To evaluate this paradigm, colchicine and vinblastine were used as neurotoxicants with a well-understood mechanism of action. These agents were only weakly cytotoxic according to the Cr-release assay, but were able to interfere with neurite outgrowth at nanomolar concentrations. Neurites that were elaborated in the presence of vinblastine and colchicine were often disfigured by numerous swellings packed with organelles. In established neurites, micromolar concentrations of vinblastine inhibited organellar motility with great rapidity, blocking all signs of transport within 20 min. The effect of colchicine was slower and less complete, but still impressive. We suggest that this four-part analysis represents a highly sensitive in vitro test for neurotoxicity, and a means of analyzing the relation between abnormalities of transport and structural damage of nerve cells.", "contents": "A paradigm for examining toxicant effects on viability, structure, and axonal transport of neurons in culture. N1E.115 murine neuroblastoma cells differentiating in serum-free medium were used to develop a paradigm for testing neurotoxicity in vitro. The paradigm was designed to test the effects of toxicants on four different aspects of cell function or structure: 1. Viability as shown by the retention of cellular radiolabel (51Cr); 2. Growth and maintenance of neurites as reflected by the incidence and average length of these processes; 3. Gross structure of neurites; and 4. Velocity and flux of rapid anterograde and retrograde axonal transport as judged by video-enhanced differential interference contrast microscopy. To evaluate this paradigm, colchicine and vinblastine were used as neurotoxicants with a well-understood mechanism of action. These agents were only weakly cytotoxic according to the Cr-release assay, but were able to interfere with neurite outgrowth at nanomolar concentrations. Neurites that were elaborated in the presence of vinblastine and colchicine were often disfigured by numerous swellings packed with organelles. In established neurites, micromolar concentrations of vinblastine inhibited organellar motility with great rapidity, blocking all signs of transport within 20 min. The effect of colchicine was slower and less complete, but still impressive. We suggest that this four-part analysis represents a highly sensitive in vitro test for neurotoxicity, and a means of analyzing the relation between abnormalities of transport and structural damage of nerve cells."} {"id": "PMID:1282328", "title": "Molecular motors in axonal transport. Cellular and molecular biology of kinesin.", "content": "Neurons require a large amount of intracellular transport. Cytoplasmic polypeptides and membrane-bounded organelles move from the perikaryon, down the length of the axon, and to the synaptic terminals. This movement occurs at distinct rates and is termed axonal transport. Axonal transport is divided into the slow transport of cytoplasmic proteins including glycolytic enzymes and cytoskeletal structures and the fast transport of membrane-bounded organelles along linear arrays of microtubules. The polypeptide compositions of the rate classes of axonal transport have been well characterized, but the underlying molecular mechanisms of this movement are less clear. Progress has been particularly slow toward understanding force-generation in slow transport, but recent developments have provided insight into the molecular motors involved in fast axonal transport. Recent advances in the cellular and molecular biology of one fast axonal transport motor, kinesin, have provided a clearer understanding of organelle movement along microtubules. The availability of cellular and molecular probes for kinesin and other putative axonal transport motors have led to a reevaluation of our understanding of intracellular motility.", "contents": "Molecular motors in axonal transport. Cellular and molecular biology of kinesin. Neurons require a large amount of intracellular transport. Cytoplasmic polypeptides and membrane-bounded organelles move from the perikaryon, down the length of the axon, and to the synaptic terminals. This movement occurs at distinct rates and is termed axonal transport. Axonal transport is divided into the slow transport of cytoplasmic proteins including glycolytic enzymes and cytoskeletal structures and the fast transport of membrane-bounded organelles along linear arrays of microtubules. The polypeptide compositions of the rate classes of axonal transport have been well characterized, but the underlying molecular mechanisms of this movement are less clear. Progress has been particularly slow toward understanding force-generation in slow transport, but recent developments have provided insight into the molecular motors involved in fast axonal transport. Recent advances in the cellular and molecular biology of one fast axonal transport motor, kinesin, have provided a clearer understanding of organelle movement along microtubules. The availability of cellular and molecular probes for kinesin and other putative axonal transport motors have led to a reevaluation of our understanding of intracellular motility."} {"id": "PMID:1282329", "title": "Organelles in fast axonal transport. What molecules do they carry in anterograde vs retrograde directions, as observed in mammalian systems?", "content": "The present minireview describes experiments carried out, in short-term crush-operated rat nerves, using immunofluorescence and cytofluorimetric scanning techniques to study endogenous substances in anterograde and retrograde fast axonal transport. Vesicle membrane components p38 (synaptophysin) and SV2 are accumulating on both sides of a crush, but a larger proportion of p38 (about 3/4) than of SV2 (about 1/2) is recycling toward the cell body, compared to the amount carried with anterograde transport. Matrix peptides, such as CGRP, ChRA, VIP, and DBH are recycling to a minor degree, although only 10-20% of surface-associated molecules, such as synapsins and kinesin, appear to recycle. The described methodological approach to study the composition of organelles in fast axonal transport, anterograde as compared to retrograde, is shown to be useful for investigating neurobiological processes. We make use of the \"in vivo chromatography\" process that the fast axonal transport system constitutes. Only substances that are in some way either stored in, or associated with, transported organelles can be clearly observed to accumulate relative to the crush region. Emphasis in this paper was given to the synapsins, because of diverging results published concerning the degree of affiliation with various neuronal organelles. Our previously published results have indicated that in the living axons the SYN I is affiliated with mainly anterogradely fast transported organelles. Therefore, some preliminary, previously unpublished results on the accumulations of the four different synapsins (SYN Ia, SYN Ib, SYN IIa, and SYN IIb), using antisera specific for each of the four members of the synapsin family, are described. It was found that SYN Ib clearly has a stronger affiliation to anterogradely transported organelles than SYN Ia, and that both SYN IIa and SYN IIb are bound to some degree to transported organelles.", "contents": "Organelles in fast axonal transport. What molecules do they carry in anterograde vs retrograde directions, as observed in mammalian systems? The present minireview describes experiments carried out, in short-term crush-operated rat nerves, using immunofluorescence and cytofluorimetric scanning techniques to study endogenous substances in anterograde and retrograde fast axonal transport. Vesicle membrane components p38 (synaptophysin) and SV2 are accumulating on both sides of a crush, but a larger proportion of p38 (about 3/4) than of SV2 (about 1/2) is recycling toward the cell body, compared to the amount carried with anterograde transport. Matrix peptides, such as CGRP, ChRA, VIP, and DBH are recycling to a minor degree, although only 10-20% of surface-associated molecules, such as synapsins and kinesin, appear to recycle. The described methodological approach to study the composition of organelles in fast axonal transport, anterograde as compared to retrograde, is shown to be useful for investigating neurobiological processes. We make use of the \"in vivo chromatography\" process that the fast axonal transport system constitutes. Only substances that are in some way either stored in, or associated with, transported organelles can be clearly observed to accumulate relative to the crush region. Emphasis in this paper was given to the synapsins, because of diverging results published concerning the degree of affiliation with various neuronal organelles. Our previously published results have indicated that in the living axons the SYN I is affiliated with mainly anterogradely fast transported organelles. Therefore, some preliminary, previously unpublished results on the accumulations of the four different synapsins (SYN Ia, SYN Ib, SYN IIa, and SYN IIb), using antisera specific for each of the four members of the synapsin family, are described. It was found that SYN Ib clearly has a stronger affiliation to anterogradely transported organelles than SYN Ia, and that both SYN IIa and SYN IIb are bound to some degree to transported organelles."} {"id": "PMID:1282330", "title": "Axon-myelin transfer of phospholipids and phospholipid precursors. Labeling of myelin phosphoinositides through axonal transport.", "content": "Previous studies have provided evidence for axon-to-myelin transfer of intact lipids and lipid precursors for reutilization by myelin enzymes. Several of the lipid constituents of myelin showed significant contralateral/ipsilateral ratios of incorporated radioactivity, indicative of axonal origin, whereas proteins and certain other lipids did not participate in this transfer-reutilization process. The present study will examine the labeling of myelin phosphoinositides by this pathway. Both 32PO4 and [3H]inositol were injected monocularly into 7-9-wk-old rabbits and myelin was isolated 7 or 21 days later from pooled optic tracts and superior colliculi. In total lipids 32P counts of the isolated myelin samples showed significant contralateral/ipsilateral ratios as well as increasing magnitude of contralateral-ipsilateral differences during the time interval. Thin-layer chromatographic isolation of the myelin phosphoinositides revealed significant 32P-labeling of these species, with PIP and PIP2 showing time-related increases. This resembled the labeling pattern of the major phospholipids from rabbit optic system myelin in a previous study and suggested incorporation of axon-derived phosphate by myelin-associated enzymes. The 32P label in PI, on the other hand, remained constant between 7 and 21 days, suggesting transfer of intact lipid. This was supported by the labeling pattern with [3H]inositol, which also showed no increase over time for PI. These results suggest axon-myelin transfer of intact PI followed by myelin-localized incorporation of axon-derived phosphate groups into PIP and PIP2. The general topic of axon-myelin transfer of phospholipids and phospholipid precursors is reviewed.", "contents": "Axon-myelin transfer of phospholipids and phospholipid precursors. Labeling of myelin phosphoinositides through axonal transport. Previous studies have provided evidence for axon-to-myelin transfer of intact lipids and lipid precursors for reutilization by myelin enzymes. Several of the lipid constituents of myelin showed significant contralateral/ipsilateral ratios of incorporated radioactivity, indicative of axonal origin, whereas proteins and certain other lipids did not participate in this transfer-reutilization process. The present study will examine the labeling of myelin phosphoinositides by this pathway. Both 32PO4 and [3H]inositol were injected monocularly into 7-9-wk-old rabbits and myelin was isolated 7 or 21 days later from pooled optic tracts and superior colliculi. In total lipids 32P counts of the isolated myelin samples showed significant contralateral/ipsilateral ratios as well as increasing magnitude of contralateral-ipsilateral differences during the time interval. Thin-layer chromatographic isolation of the myelin phosphoinositides revealed significant 32P-labeling of these species, with PIP and PIP2 showing time-related increases. This resembled the labeling pattern of the major phospholipids from rabbit optic system myelin in a previous study and suggested incorporation of axon-derived phosphate by myelin-associated enzymes. The 32P label in PI, on the other hand, remained constant between 7 and 21 days, suggesting transfer of intact lipid. This was supported by the labeling pattern with [3H]inositol, which also showed no increase over time for PI. These results suggest axon-myelin transfer of intact PI followed by myelin-localized incorporation of axon-derived phosphate groups into PIP and PIP2. The general topic of axon-myelin transfer of phospholipids and phospholipid precursors is reviewed."} {"id": "PMID:1282331", "title": "Does nerve impulse activity modulate fast axonal transport?", "content": "The possibility that the amount of newly synthesized material made available for fast axonal transport is regulated by nerve impulse activity was examined in an in vitro preparation of bullfrog dorsal root ganglia (DRG) and sciatic nerve. Under conditions that precluded effects of impulse activity on either uptake or incorporation of precursor, patterned stimulation of the sciatic nerve (1 out of every 2 s) produced a frequency- and time-dependent decrease in the amount of radiolabeled protein accumulating at a nerve ligature. The response to patterned stimulation was significantly greater than that to continuous stimulation when the same number of stimuli were delivered. In unligated nerve preparations, patterned stimulation decreased the amplitude of the transport profile with no concomitant change in the wave front distance. Nerve stimulation produced no observable ultrastructural alterations within neuronal cell bodies of the DRG. We propose that the physiological significance of these results is not that nerve impulse activity decreases fast axonal transport, but that the amount of transport increases during periods of electrical quiescence. According to this hypothesis, activity-dependent macromolecules of the axolemma and nerve terminals are replenished during periods when the neuron is firing less frequently. These findings are discussed in light of reports that chronic in vivo stimulation increases the amount of fast-transported, radiolabeled protein (Chan et al., 1989) and that TTX-blockade of neuronal activity has no effect on protein transport (Edwards and Grafstein, 1984; Riccio and Matthews, 1985).", "contents": "Does nerve impulse activity modulate fast axonal transport? The possibility that the amount of newly synthesized material made available for fast axonal transport is regulated by nerve impulse activity was examined in an in vitro preparation of bullfrog dorsal root ganglia (DRG) and sciatic nerve. Under conditions that precluded effects of impulse activity on either uptake or incorporation of precursor, patterned stimulation of the sciatic nerve (1 out of every 2 s) produced a frequency- and time-dependent decrease in the amount of radiolabeled protein accumulating at a nerve ligature. The response to patterned stimulation was significantly greater than that to continuous stimulation when the same number of stimuli were delivered. In unligated nerve preparations, patterned stimulation decreased the amplitude of the transport profile with no concomitant change in the wave front distance. Nerve stimulation produced no observable ultrastructural alterations within neuronal cell bodies of the DRG. We propose that the physiological significance of these results is not that nerve impulse activity decreases fast axonal transport, but that the amount of transport increases during periods of electrical quiescence. According to this hypothesis, activity-dependent macromolecules of the axolemma and nerve terminals are replenished during periods when the neuron is firing less frequently. These findings are discussed in light of reports that chronic in vivo stimulation increases the amount of fast-transported, radiolabeled protein (Chan et al., 1989) and that TTX-blockade of neuronal activity has no effect on protein transport (Edwards and Grafstein, 1984; Riccio and Matthews, 1985)."} {"id": "PMID:1282332", "title": "Acrylamide-induced alterations in axonal transport. Biochemical and autoradiographic studies.", "content": "Alterations in the axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve were examined in adult male rats exposed to acrylamide (40 mg ip/kg body wt/d for nine consecutive days). Twenty-four hours after the last dose, the L5 dorsal root ganglion (DRG) was injected with either [35S]methionine to label proteins or [3H]glucosamine to label glycoproteins and gangliosides. The downflow patterns of radioactivity for [35S]methionine-labeled proteins and [3H]glucosamine-labeled gangliosides were unaltered by acrylamide treatment. In contrast, the outflow pattern of labeled glycoproteins displayed a severely attenuated crest with no alteration in velocity, suggesting a preferential transfer with the unlabeled stationary components in the axolemma. Retrograde accumulation of transported glycoproteins and gangliosides was unaltered for at least 6 h; however, by 24 h, there was a 75% decrease in the amount of accumulated material. The accumulation of [35S]methionine-labeled proteins was not altered. Autoradiographic analysis revealed an acrylamide-induced paucity of transported radiolabeled glycoproteins selectively in myelinated axons with no effect on \"nonmyelinated\" axons. The pattern of transported proteins was similar in both control and acrylamide-exposed animals. These results suggest a preferential inhibition of glycosylation or axonal transport of glycoproteins in neurons bearing myelinated axons. More importantly, it suggests that interpretations of axonal transport data must be made with the consideration of alterations in selective nerve fibers and not with the tacit assumption that all fibers in the nerve population are equally affected.", "contents": "Acrylamide-induced alterations in axonal transport. Biochemical and autoradiographic studies. Alterations in the axonal transport of proteins, glycoproteins, and gangliosides in sensory neurons of the sciatic nerve were examined in adult male rats exposed to acrylamide (40 mg ip/kg body wt/d for nine consecutive days). Twenty-four hours after the last dose, the L5 dorsal root ganglion (DRG) was injected with either [35S]methionine to label proteins or [3H]glucosamine to label glycoproteins and gangliosides. The downflow patterns of radioactivity for [35S]methionine-labeled proteins and [3H]glucosamine-labeled gangliosides were unaltered by acrylamide treatment. In contrast, the outflow pattern of labeled glycoproteins displayed a severely attenuated crest with no alteration in velocity, suggesting a preferential transfer with the unlabeled stationary components in the axolemma. Retrograde accumulation of transported glycoproteins and gangliosides was unaltered for at least 6 h; however, by 24 h, there was a 75% decrease in the amount of accumulated material. The accumulation of [35S]methionine-labeled proteins was not altered. Autoradiographic analysis revealed an acrylamide-induced paucity of transported radiolabeled glycoproteins selectively in myelinated axons with no effect on \"nonmyelinated\" axons. The pattern of transported proteins was similar in both control and acrylamide-exposed animals. These results suggest a preferential inhibition of glycosylation or axonal transport of glycoproteins in neurons bearing myelinated axons. More importantly, it suggests that interpretations of axonal transport data must be made with the consideration of alterations in selective nerve fibers and not with the tacit assumption that all fibers in the nerve population are equally affected."} {"id": "PMID:1282333", "title": "Regeneration of an adult peripheral nerve preparation in culture.", "content": "The methods used to maintain the vagus nerve from the adult rat in culture and how regeneration is studied in this preparation are described. A hypothesis is presented on the triggering of the cell body reaction. It is suggested that this reaction is initiated by proteins synthesized in nonneuronal cells at the site of a nerve lesion. These proteins, referred to as regenerins, reach the nerve cell body by retrograde axonal transport, where they initiate the regeneration process.", "contents": "Regeneration of an adult peripheral nerve preparation in culture. The methods used to maintain the vagus nerve from the adult rat in culture and how regeneration is studied in this preparation are described. A hypothesis is presented on the triggering of the cell body reaction. It is suggested that this reaction is initiated by proteins synthesized in nonneuronal cells at the site of a nerve lesion. These proteins, referred to as regenerins, reach the nerve cell body by retrograde axonal transport, where they initiate the regeneration process."} {"id": "PMID:1282334", "title": "Neuronal compartments and axonal transport of synapsin I.", "content": "Studies on the transport kinetics and the posttranslational modification of synapsin I in mouse retinal ganglion cells were performed to obtain an insight into the possible factors involved in forming the structural and functional differences between the axon and its terminals. Synapsin I, a neuronal phosphoprotein associated with small synaptic vesicles and cytoskeletal elements at the presynaptic terminals, is thought to be involved in modulating neurotransmitter release. The state of phosphorylation of synapsin I in vitro regulates its interaction with both synaptic vesicles and cytoskeletal components, including microtubules and microfilaments. Here we present the first evidence that in the mouse retinal ganglion cells most synapsin I is transported down the axon, together with the cytomatrix proteins, at the same rate as the slow component b of axonal transport, and is phosphorylated at both the head and tail regions. In addition, our data suggest that, after synapsin I has reached the nerve endings, the relative proportions of variously phosphorylated synapsin I molecules change, and that these changes lead to a decrease in the overall content of phosphorus. These results are consistent with the hypothesis that, in vivo, the phosphorylation of synapsin I along the axon prevents the formation of a dense network that could impair organelle movement. On the other hand, the dephosphorylation of synapsin I at the nerve endings may regulate the clustering of small synaptic vesicles and modulate neurotransmitter release by controlling the availability of small synaptic vesicles for exocytosis.", "contents": "Neuronal compartments and axonal transport of synapsin I. Studies on the transport kinetics and the posttranslational modification of synapsin I in mouse retinal ganglion cells were performed to obtain an insight into the possible factors involved in forming the structural and functional differences between the axon and its terminals. Synapsin I, a neuronal phosphoprotein associated with small synaptic vesicles and cytoskeletal elements at the presynaptic terminals, is thought to be involved in modulating neurotransmitter release. The state of phosphorylation of synapsin I in vitro regulates its interaction with both synaptic vesicles and cytoskeletal components, including microtubules and microfilaments. Here we present the first evidence that in the mouse retinal ganglion cells most synapsin I is transported down the axon, together with the cytomatrix proteins, at the same rate as the slow component b of axonal transport, and is phosphorylated at both the head and tail regions. In addition, our data suggest that, after synapsin I has reached the nerve endings, the relative proportions of variously phosphorylated synapsin I molecules change, and that these changes lead to a decrease in the overall content of phosphorus. These results are consistent with the hypothesis that, in vivo, the phosphorylation of synapsin I along the axon prevents the formation of a dense network that could impair organelle movement. On the other hand, the dephosphorylation of synapsin I at the nerve endings may regulate the clustering of small synaptic vesicles and modulate neurotransmitter release by controlling the availability of small synaptic vesicles for exocytosis."} {"id": "PMID:1282338", "title": "Rhodamine-labelled phalloidin stains components in the chromosomal spindle fibres of crane-fly spermatocytes and Haemanthus endosperm cells.", "content": "In crane-fly spermatocytes and Haemanthus endosperm, all metaphase and anaphase chromosomal spindle fibres were stained with rhodamine-labelled phalloidin. In crane-fly spermatocytes, each kinetochore was stained with rhodamine-labelled phalloidin at diakinesis of prophase and after colcemid caused metaphase spindles to depolymerize. Since phalloidin stains actin filaments, the distributions of rhodamine-labelled phalloidin-stained material in crane-fly spermatocytes and Haemanthus endosperm suggest that actin filaments might interact with microtubules to produce forces that move chromosomes during cell division, either directly or via an intermediate motor molecule.", "contents": "Rhodamine-labelled phalloidin stains components in the chromosomal spindle fibres of crane-fly spermatocytes and Haemanthus endosperm cells. In crane-fly spermatocytes and Haemanthus endosperm, all metaphase and anaphase chromosomal spindle fibres were stained with rhodamine-labelled phalloidin. In crane-fly spermatocytes, each kinetochore was stained with rhodamine-labelled phalloidin at diakinesis of prophase and after colcemid caused metaphase spindles to depolymerize. Since phalloidin stains actin filaments, the distributions of rhodamine-labelled phalloidin-stained material in crane-fly spermatocytes and Haemanthus endosperm suggest that actin filaments might interact with microtubules to produce forces that move chromosomes during cell division, either directly or via an intermediate motor molecule."} {"id": "PMID:1282335", "title": "Relationships between the rapid axonal transport of newly synthesized proteins and membranous organelles.", "content": "Rapid axonal transport is generally viewed as being exactly analogous to the secretory process in nonneuronal cells. The cell biology of rapid axonal transport is reviewed, the central concern being to explore those aspects that do not fit into the general secretory model and which may thus represent specific neuronal adaptations. Particular attention is paid to the relationship between the transport of newly synthesized proteins and of the membranous organelles that act as carriers. Sites in the transport sequence at which the behavior of axonal transport may differ from the secretory model are at the initiation of axonal transport at the trans-side of the Golgi apparatus, within the axon where molecules are deposited from the moving phase to a stationary phase, and at nerve terminals or axonal lesions where transport reversal takes place.", "contents": "Relationships between the rapid axonal transport of newly synthesized proteins and membranous organelles. Rapid axonal transport is generally viewed as being exactly analogous to the secretory process in nonneuronal cells. The cell biology of rapid axonal transport is reviewed, the central concern being to explore those aspects that do not fit into the general secretory model and which may thus represent specific neuronal adaptations. Particular attention is paid to the relationship between the transport of newly synthesized proteins and of the membranous organelles that act as carriers. Sites in the transport sequence at which the behavior of axonal transport may differ from the secretory model are at the initiation of axonal transport at the trans-side of the Golgi apparatus, within the axon where molecules are deposited from the moving phase to a stationary phase, and at nerve terminals or axonal lesions where transport reversal takes place."} {"id": "PMID:1282336", "title": "Organization and slow axonal transport of cytoskeletal proteins under normal and regenerating conditions.", "content": "The organization of the axonal cytoskeleton was investigated by analyzing the solubility and transport profile of the major cytoskeletal proteins in motor axons of the rat sciatic nerve under normal and regenerating conditions. When extracted with the Triton-containing buffer at low temperature, 50% of tubulin and 30% of actin were recovered in the insoluble form resistant to further depolymerizing treatments. Most of this cold-insoluble form was transported in slow component a (SCa), the slower of the two subcomponents of slow axonal transport, whereas the cold-soluble form showed a biphasic distribution between SCa and SCb (slow component b). Changes in slow transport during regeneration were studied by injuring the nerve either prior to (experiment I) or after (experiment II) radioactive labeling. In experiment I where the transport of proteins synthesized in response to injury was examined, selective acceleration of SCb was detected together with an increase in the relative proportion of this component. In experiment II where the response of the preexisting cytoskeleton was examined, a shift from SCa to SCb of the cold-soluble form was observed. The differential distribution and response of the two forms of tubulin and actin suggest that the cold-soluble form may be more directly involved in axonal transport.", "contents": "Organization and slow axonal transport of cytoskeletal proteins under normal and regenerating conditions. The organization of the axonal cytoskeleton was investigated by analyzing the solubility and transport profile of the major cytoskeletal proteins in motor axons of the rat sciatic nerve under normal and regenerating conditions. When extracted with the Triton-containing buffer at low temperature, 50% of tubulin and 30% of actin were recovered in the insoluble form resistant to further depolymerizing treatments. Most of this cold-insoluble form was transported in slow component a (SCa), the slower of the two subcomponents of slow axonal transport, whereas the cold-soluble form showed a biphasic distribution between SCa and SCb (slow component b). Changes in slow transport during regeneration were studied by injuring the nerve either prior to (experiment I) or after (experiment II) radioactive labeling. In experiment I where the transport of proteins synthesized in response to injury was examined, selective acceleration of SCb was detected together with an increase in the relative proportion of this component. In experiment II where the response of the preexisting cytoskeleton was examined, a shift from SCa to SCb of the cold-soluble form was observed. The differential distribution and response of the two forms of tubulin and actin suggest that the cold-soluble form may be more directly involved in axonal transport."} {"id": "PMID:1282337", "title": "Transport of receptors.", "content": "The axonal transport of neurotransmitter receptors is thought to be a common phenomenon in many neuronal systems. The \"machinery\" for receptor (protein) \"assembly\" is found in the cell bodies of neurons and the \"manufacture\" of receptors takes place there. These receptors are then \"shipped\" to their ultimate destinations by a transport process. This is an axonal transport mechanism in the case of presynaptic receptors. Some form of transport process may also exist to send receptors out into the dendritic arborizations of neurons, although the latter is more difficult to verify. Axonal transport has been demonstrated, in the peripheral nervous system, for many different neurotransmitter receptors. In the central nervous system, the results are less clear, but indicate the presence of a transport mechanism for catecholamine, acetylcholine, and opiate sites. One important component then, in the development of receptors, is the transportation to terminal membrane sites where they are ultimately incorporated and available for interaction with neurotransmitters and drugs.", "contents": "Transport of receptors. The axonal transport of neurotransmitter receptors is thought to be a common phenomenon in many neuronal systems. The \"machinery\" for receptor (protein) \"assembly\" is found in the cell bodies of neurons and the \"manufacture\" of receptors takes place there. These receptors are then \"shipped\" to their ultimate destinations by a transport process. This is an axonal transport mechanism in the case of presynaptic receptors. Some form of transport process may also exist to send receptors out into the dendritic arborizations of neurons, although the latter is more difficult to verify. Axonal transport has been demonstrated, in the peripheral nervous system, for many different neurotransmitter receptors. In the central nervous system, the results are less clear, but indicate the presence of a transport mechanism for catecholamine, acetylcholine, and opiate sites. One important component then, in the development of receptors, is the transportation to terminal membrane sites where they are ultimately incorporated and available for interaction with neurotransmitters and drugs."} {"id": "PMID:1282341", "title": "Improved indirect fluorescence immunocytochemical method using counterstains.", "content": "Immunocytochemistry in recent years has provided powerful tools for research in neurobiology. One of the more popular techniques is the indirect fluorescence technique in which fluorescein isothiocyanate (FITC) or tetrahodamine isothiocyanate (TRITC) is used. Although widely used, this technique has two disadvantages: (1) localization may be difficult in relation to background morphology, and (2) the fluorescence fades. The study reported here describes a modification of an indirect immunocytochemical technique using FITC, TRITC and 7-amino-4-methyl-coumarin-3-acetic acid (AMCA) which enhances localization and significantly prolongs fluorescence. Evans blue was used as a counterstain. The results show that FITC and AMCA stained cells are seen against a background of clearly distinguishable cells after counterstaining with Evans blue. However, Evans blue is not compatible with TRITC. In addition, the fluorescence life of the FITC is extended from several days to several weeks with Evans blue. These results clearly indicate that Evans blue can be used to improve indirect fluorescence immunocytochemical techniques.", "contents": "Improved indirect fluorescence immunocytochemical method using counterstains. Immunocytochemistry in recent years has provided powerful tools for research in neurobiology. One of the more popular techniques is the indirect fluorescence technique in which fluorescein isothiocyanate (FITC) or tetrahodamine isothiocyanate (TRITC) is used. Although widely used, this technique has two disadvantages: (1) localization may be difficult in relation to background morphology, and (2) the fluorescence fades. The study reported here describes a modification of an indirect immunocytochemical technique using FITC, TRITC and 7-amino-4-methyl-coumarin-3-acetic acid (AMCA) which enhances localization and significantly prolongs fluorescence. Evans blue was used as a counterstain. The results show that FITC and AMCA stained cells are seen against a background of clearly distinguishable cells after counterstaining with Evans blue. However, Evans blue is not compatible with TRITC. In addition, the fluorescence life of the FITC is extended from several days to several weeks with Evans blue. These results clearly indicate that Evans blue can be used to improve indirect fluorescence immunocytochemical techniques."} {"id": "PMID:1282342", "title": "DiI as a marker for cellular transplantation into solid organs.", "content": "Research in cellular transplantation is frequently compromised by an inability to identify transplanted cells engrafting into orthotopic sites if they exhibit normal morphology and no unique antigenic markers. A method is described for using the fluorescent dye DiI as a marker for cell transplantation studies. This dye is not metabolized or exchanged between cells in vitro or in vivo and enables identification of engrafted cells by fluorescence microscopy, flow cytometry or fluorescence-activated cell sorting. Applications are described in autologous hepatocellular and thyroid follicular cell transplantation.", "contents": "DiI as a marker for cellular transplantation into solid organs. Research in cellular transplantation is frequently compromised by an inability to identify transplanted cells engrafting into orthotopic sites if they exhibit normal morphology and no unique antigenic markers. A method is described for using the fluorescent dye DiI as a marker for cell transplantation studies. This dye is not metabolized or exchanged between cells in vitro or in vivo and enables identification of engrafted cells by fluorescence microscopy, flow cytometry or fluorescence-activated cell sorting. Applications are described in autologous hepatocellular and thyroid follicular cell transplantation."} {"id": "PMID:1282346", "title": "Synthesis of digoxigenin-labeled cDNA as a test for mRNA integrity.", "content": "The nucleotide analogue digoxigenin-11-dUTP is widely used as a nonradioactive marker in a broad range of techniques including dot blots, Southern and Northern blots, colony and plaque screenings and in situ hybridizations. In this report, we describe the incorporation of this molecule into a cDNA synthesized by reverse transcriptase as a novel application for digoxigenin. This reaction can be performed as a useful control to check the integrity of a bulk mRNA preparation in the construction of a cDNA library, since the ability of mRNA to direct the synthesis of long molecules of first-strand cDNA is a sign of its integrity.", "contents": "Synthesis of digoxigenin-labeled cDNA as a test for mRNA integrity. The nucleotide analogue digoxigenin-11-dUTP is widely used as a nonradioactive marker in a broad range of techniques including dot blots, Southern and Northern blots, colony and plaque screenings and in situ hybridizations. In this report, we describe the incorporation of this molecule into a cDNA synthesized by reverse transcriptase as a novel application for digoxigenin. This reaction can be performed as a useful control to check the integrity of a bulk mRNA preparation in the construction of a cDNA library, since the ability of mRNA to direct the synthesis of long molecules of first-strand cDNA is a sign of its integrity."} {"id": "PMID:1282347", "title": "Flavonoid-specific staining of Arabidopsis thaliana.", "content": "Crop yields may be threatened by increases in UV-B radiation resulting from depletion of the ozone layer. In higher plants, the presence of flavonols provides a protective mechanism, and we report a novel staining procedure for the visualization of such protectants in plant tissue. It is shown that the proposed technique provides sensitive and specific fluorescence of flavonoids in chlorophyll-bleached tissue of Arabidopsis thaliana.", "contents": "Flavonoid-specific staining of Arabidopsis thaliana. Crop yields may be threatened by increases in UV-B radiation resulting from depletion of the ozone layer. In higher plants, the presence of flavonols provides a protective mechanism, and we report a novel staining procedure for the visualization of such protectants in plant tissue. It is shown that the proposed technique provides sensitive and specific fluorescence of flavonoids in chlorophyll-bleached tissue of Arabidopsis thaliana."} {"id": "PMID:1282348", "title": "Development of a rapid method for detecting bacterial cells in situ using 16S rRNA-targeted probes.", "content": "A rapid method for the identification of bacterial cells using 16S rRNA-directed, fluorescently tagged oligonucleotide probes has been developed. The parameters evaluated for their effect on labeling intensity included storage time, type of fixative, time of fixation, treatment time with methanol:formaldehyde and treatment time with borohydride. The results of tests using a variety of microorganisms, both Gram-positive and Gram-negative, are presented. Using this method, cells are spotted onto slides and stored desiccated until hybridized. This method may be especially applicable to environmental samples, which comprise diverse cell types and frequently require storage prior to examination.", "contents": "Development of a rapid method for detecting bacterial cells in situ using 16S rRNA-targeted probes. A rapid method for the identification of bacterial cells using 16S rRNA-directed, fluorescently tagged oligonucleotide probes has been developed. The parameters evaluated for their effect on labeling intensity included storage time, type of fixative, time of fixation, treatment time with methanol:formaldehyde and treatment time with borohydride. The results of tests using a variety of microorganisms, both Gram-positive and Gram-negative, are presented. Using this method, cells are spotted onto slides and stored desiccated until hybridized. This method may be especially applicable to environmental samples, which comprise diverse cell types and frequently require storage prior to examination."} {"id": "PMID:1282349", "title": "Cisplatinum dose dependent response in germ cell cancer evaluated by tumour marker modelling.", "content": "This study presents an analysis on longitudinal tumour marker series in twenty-two patients with non-seminomatous germ cell cancers treated with cisplatinum (DDP) based combination chemotherapy. Series of alphafoetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactate dehydrogenase (LDH) were analyzed applying a dynamic mathematical marker model. The model analysis provided quantitated values for growth rate and treatment response in the marker producing cells. The analysis showed that LDH had to be above 2,000 U/l to be a trustworthy tumour marker. HCG producing cells tended to grow faster than AFP producing cells, and were 3-5-fold more sensitive to the chemotherapy given than AFP producing cells. Treatment response versus DDP dose appeared to be bi-phasic, but with no significant change in treatment efficiency within the given range of DDP doses.", "contents": "Cisplatinum dose dependent response in germ cell cancer evaluated by tumour marker modelling. This study presents an analysis on longitudinal tumour marker series in twenty-two patients with non-seminomatous germ cell cancers treated with cisplatinum (DDP) based combination chemotherapy. Series of alphafoetoprotein (AFP), human chorionic gonadotrophin (HCG) and lactate dehydrogenase (LDH) were analyzed applying a dynamic mathematical marker model. The model analysis provided quantitated values for growth rate and treatment response in the marker producing cells. The analysis showed that LDH had to be above 2,000 U/l to be a trustworthy tumour marker. HCG producing cells tended to grow faster than AFP producing cells, and were 3-5-fold more sensitive to the chemotherapy given than AFP producing cells. Treatment response versus DDP dose appeared to be bi-phasic, but with no significant change in treatment efficiency within the given range of DDP doses."} {"id": "PMID:1282350", "title": "Hepatic DNA methylation in young, middle-aged, and senescent rats: the effect of mitogen-induced cell proliferation.", "content": "We have investigated the effect of a single dose of the hepatomitogen lead nitrate on the 5-methyldeoxycytidine (5-mdcyd) content and the HpaII, MspI, and HaeIII restriction patterns of hepatic DNA from young, middle-aged, and senescent rats. It was found that (i) the methylation pattern of genomic DNA changed significantly with age and (ii) the methylation patterns were differentially affected by the liver mitogen in the three cell populations here considered.", "contents": "Hepatic DNA methylation in young, middle-aged, and senescent rats: the effect of mitogen-induced cell proliferation. We have investigated the effect of a single dose of the hepatomitogen lead nitrate on the 5-methyldeoxycytidine (5-mdcyd) content and the HpaII, MspI, and HaeIII restriction patterns of hepatic DNA from young, middle-aged, and senescent rats. It was found that (i) the methylation pattern of genomic DNA changed significantly with age and (ii) the methylation patterns were differentially affected by the liver mitogen in the three cell populations here considered."} {"id": "PMID:1282358", "title": "Tenascin expression in basal cell carcinoma.", "content": "Tenascin (hexabrachion, cytotactin) is an extracellular matrix glycoprotein whose expression is strongly increased in hyperproliferative skin diseases, as shown by immunohistochemistry with polyclonal sera. In this study we describe a new monoclonal antibody (T2H5) against human tenascin. The specificity of T2H5 was validated by sequential immunoprecipitation of tenascin with polyclonal sera. T2H5 was used to analyse the presence of tenascin in basal cell carcinoma. Using Western blotting, at least two forms of tenascin were found, with approximate molecular weights of 210 and 300 kDa. In cultured human skin fibroblasts only the high molecular weight form was found.", "contents": "Tenascin expression in basal cell carcinoma. Tenascin (hexabrachion, cytotactin) is an extracellular matrix glycoprotein whose expression is strongly increased in hyperproliferative skin diseases, as shown by immunohistochemistry with polyclonal sera. In this study we describe a new monoclonal antibody (T2H5) against human tenascin. The specificity of T2H5 was validated by sequential immunoprecipitation of tenascin with polyclonal sera. T2H5 was used to analyse the presence of tenascin in basal cell carcinoma. Using Western blotting, at least two forms of tenascin were found, with approximate molecular weights of 210 and 300 kDa. In cultured human skin fibroblasts only the high molecular weight form was found."} {"id": "PMID:1282356", "title": "Electron microscopy of alpha 2-macroglobulin with a thiol ester bound ligand.", "content": "In order to covalently bind the hydrolyzed thiol ester groups of the human alpha 2-macroglobulin (alpha 2M) transformed by methylamine, the phospholipase A2 (PLA2), a small enzyme (M(r) = 13,000) from Naja nigricollis snake venom was activated by succinimidyl 4-(maleimidomethyl)cyclohexane-1-carboxylate (SMCC). Average images determined from electron micrographs of the methylamine-transformed alpha 2M, with and without activated PLA2, were determined by image processing and compared. A localization of the PLA2 was achieved by subtracting the average image of alpha 2M transformed by methylamine from that containing PLA2. The results are consistent with previous work showing the central localization of chymotrypsin trapped in alpha 2M. They also suggest that the four thiol esters are located near the center of the alpha 2M molecule.", "contents": "Electron microscopy of alpha 2-macroglobulin with a thiol ester bound ligand. In order to covalently bind the hydrolyzed thiol ester groups of the human alpha 2-macroglobulin (alpha 2M) transformed by methylamine, the phospholipase A2 (PLA2), a small enzyme (M(r) = 13,000) from Naja nigricollis snake venom was activated by succinimidyl 4-(maleimidomethyl)cyclohexane-1-carboxylate (SMCC). Average images determined from electron micrographs of the methylamine-transformed alpha 2M, with and without activated PLA2, were determined by image processing and compared. A localization of the PLA2 was achieved by subtracting the average image of alpha 2M transformed by methylamine from that containing PLA2. The results are consistent with previous work showing the central localization of chymotrypsin trapped in alpha 2M. They also suggest that the four thiol esters are located near the center of the alpha 2M molecule."} {"id": "PMID:1282359", "title": "Substance P induces intracellular calcium increase and translocation of protein kinase C in epidermis.", "content": "Substance P is a neuropeptide present in, and released from, peripheral C nerve endings. The presence of substance P-positive nerve fibres in the epidermis has been reported. We investigated the effect of substance P on the transmembrane signalling system of pig epidermal keratinocytes. Treatment of pig epidermis with substance P resulted in an increase in inositol 1,4,5-trisphosphate (IP3), and in intracellular free calcium. The treatment also resulted in translocation of protein kinase C from a cytosol to a membrane fraction. Substance P, however, did not affect the beta-adrenergic- or histamine (H2)- adenylate cyclase responses of the epidermis. Neither forskolin-induced, nor cholera toxin-induced cyclic AMP accumulation were affected by substance P treatment. These results consistent with the view that substance P stimulates phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis of keratinocytes, resulting in IP3-Ca2+ and diacylglycerol-protein kinase C signal activation. Although protein kinase C is known to affect the epidermal adenylate cyclase system, no evidence for such 'cross-talk regulation' was detected in keratinocytes by substance P treatment.", "contents": "Substance P induces intracellular calcium increase and translocation of protein kinase C in epidermis. Substance P is a neuropeptide present in, and released from, peripheral C nerve endings. The presence of substance P-positive nerve fibres in the epidermis has been reported. We investigated the effect of substance P on the transmembrane signalling system of pig epidermal keratinocytes. Treatment of pig epidermis with substance P resulted in an increase in inositol 1,4,5-trisphosphate (IP3), and in intracellular free calcium. The treatment also resulted in translocation of protein kinase C from a cytosol to a membrane fraction. Substance P, however, did not affect the beta-adrenergic- or histamine (H2)- adenylate cyclase responses of the epidermis. Neither forskolin-induced, nor cholera toxin-induced cyclic AMP accumulation were affected by substance P treatment. These results consistent with the view that substance P stimulates phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis of keratinocytes, resulting in IP3-Ca2+ and diacylglycerol-protein kinase C signal activation. Although protein kinase C is known to affect the epidermal adenylate cyclase system, no evidence for such 'cross-talk regulation' was detected in keratinocytes by substance P treatment."} {"id": "PMID:1282360", "title": "Recurrent annular erythema associated with anti-SS-B/La antibodies: analysis of the disease-specific epitope.", "content": "We have found that anti-SS-B/La antibodies are present in a group of patients with a characteristic recurrent annular erythema, and immunological abnormalities. The presence of a disease-specific epitope for this entity has been examined by comparing immunological reactivity of anti-SS-B/La antibodies between these patients and patients with classical Sj\u00f6gren's syndrome who have anti-SS-B/La antibodies but do not have this characteristic erythema. In immunoblotting using three different antigen sources, all the sera from both groups exhibited the same reaction patterns. V8 protease mapping showed that the sera could be divided into three groups by the difference in reactivity to two main digested peptide fragments. However, no significant relationship of the reactivity in peptide mapping between the two patient groups was observed. Further studies are necessary to elucidate the role of anti-SS-B/La antibodies in disease pathogenesis in these patients, in particular by more precise peptide mapping using recombinant SS-B/La antigen proteins.", "contents": "Recurrent annular erythema associated with anti-SS-B/La antibodies: analysis of the disease-specific epitope. We have found that anti-SS-B/La antibodies are present in a group of patients with a characteristic recurrent annular erythema, and immunological abnormalities. The presence of a disease-specific epitope for this entity has been examined by comparing immunological reactivity of anti-SS-B/La antibodies between these patients and patients with classical Sj\u00f6gren's syndrome who have anti-SS-B/La antibodies but do not have this characteristic erythema. In immunoblotting using three different antigen sources, all the sera from both groups exhibited the same reaction patterns. V8 protease mapping showed that the sera could be divided into three groups by the difference in reactivity to two main digested peptide fragments. However, no significant relationship of the reactivity in peptide mapping between the two patient groups was observed. Further studies are necessary to elucidate the role of anti-SS-B/La antibodies in disease pathogenesis in these patients, in particular by more precise peptide mapping using recombinant SS-B/La antigen proteins."} {"id": "PMID:1282361", "title": "Cytophagic histiocytic panniculitis: a report of four cases.", "content": "Four patients presented with a clinical picture of spiking fever, erythematous nodular subcutaneous skin lesions, anaemia and leucopenia. Inconstant features were weight loss (3/4), splenomegaly (3/4), thrombocytopenia (3/4), raised liver enzymes (3/4), hepatomegaly (2/4) and serosal effusions (2/4). The histopathological findings of lobular histiocytic panniculitis with 'bean-bag' cells were characteristic of cytophagic histiocytic panniculitis (CHP). No infectious agent could be detected, and there was no histological evidence of malignant neoplasia. Unlike most previously described patients with CHP, three of our four patients responded to treatment with immunosuppressive or cytostatic drugs.", "contents": "Cytophagic histiocytic panniculitis: a report of four cases. Four patients presented with a clinical picture of spiking fever, erythematous nodular subcutaneous skin lesions, anaemia and leucopenia. Inconstant features were weight loss (3/4), splenomegaly (3/4), thrombocytopenia (3/4), raised liver enzymes (3/4), hepatomegaly (2/4) and serosal effusions (2/4). The histopathological findings of lobular histiocytic panniculitis with 'bean-bag' cells were characteristic of cytophagic histiocytic panniculitis (CHP). No infectious agent could be detected, and there was no histological evidence of malignant neoplasia. Unlike most previously described patients with CHP, three of our four patients responded to treatment with immunosuppressive or cytostatic drugs."} {"id": "PMID:1282362", "title": "Association of proteins in acidic solutions--a case study with beta-globulin.", "content": "The investigation of the effect of acid pH on the structure of beta-globulin indicated several transitions as a function of pH. Upon reducing the pH from 7.0, the beta-globulin molecule underwent an expansion due to hydration up to pH 5.0, and a further increase in H+ concentration resulted in unfolding. This is a single step cooperative denaturation as indicated by the viscosity profile. At extreme acid pH values (below pH 2.0) the protein associates or folds to a different conformational motif as shown by blue shift of ultraviolet fluorescence emission maximum and decrease in reduced viscosity values by more than 30% due to an entropically driven hydrophobic interaction. The conformational analysis of beta-globulin showed a decrease up to pH 3.0, followed by an increase in the ordered structure at low pH values indicating that the low pH values stabilized this new conformation. These results are discussed in view of the molten globule structure of proteins.", "contents": "Association of proteins in acidic solutions--a case study with beta-globulin. The investigation of the effect of acid pH on the structure of beta-globulin indicated several transitions as a function of pH. Upon reducing the pH from 7.0, the beta-globulin molecule underwent an expansion due to hydration up to pH 5.0, and a further increase in H+ concentration resulted in unfolding. This is a single step cooperative denaturation as indicated by the viscosity profile. At extreme acid pH values (below pH 2.0) the protein associates or folds to a different conformational motif as shown by blue shift of ultraviolet fluorescence emission maximum and decrease in reduced viscosity values by more than 30% due to an entropically driven hydrophobic interaction. The conformational analysis of beta-globulin showed a decrease up to pH 3.0, followed by an increase in the ordered structure at low pH values indicating that the low pH values stabilized this new conformation. These results are discussed in view of the molten globule structure of proteins."} {"id": "PMID:1282363", "title": "Effects of N-terminal extension peptides on the structure and stability of bovine pancreatic trypsin inhibitor studied by 1H n.m.r.", "content": "Four N-terminal extended species of the wild-type bovine pancreatic trypsin inhibitor (WT-BPTI), Arg-BPTI (1-BPTI), Met-Glu-Ala-Glu-BPTI (4-BPTI), Ser-Ile-Glu-Gly-Arg-BPTI (5-BPTI) and Gly-Ser-Ile-Glu-Gly-Arg-BPTI (6-BPTI) have been studied by 1H n.m.r. The overall structure of the protein is largely unaffected by the addition of extension peptides. pH titration effects on the C-terminal Ala 58 H beta chemical shift indicate that the structure of 1-BPTI at neutral pH is very similar to that of the WT protein, with a salt bridge between the main chain terminal charges. A salt bridge interaction is prevented by addition of the longer extension peptides. Temperature stabilities are measured by high temperature hydrogen isotope exchange and by microcalorimetry. The stability of 1-BPTI is equal to that of WT-BPTI. A slight decrease in stability is observed for longer extensions, following the order WT-BPTI = 1-BPTI < 5-BPTI = 6-BPTI < 4-BPTI. Small changes in chemical shift are observed for 30 invariant resonances in 4-, 5- and 6-BPTI and for a subset of this group in 1-BPTI. These protons are distributed over about half of the BPTI molecule. The size of the chemical shift changes for many resonances follow the same ranking as the temperature stability. The chemical shift effects are attributed to charge and dielectric effects from extension peptides that probably share a common orientation on the surface of BPTI.", "contents": "Effects of N-terminal extension peptides on the structure and stability of bovine pancreatic trypsin inhibitor studied by 1H n.m.r. Four N-terminal extended species of the wild-type bovine pancreatic trypsin inhibitor (WT-BPTI), Arg-BPTI (1-BPTI), Met-Glu-Ala-Glu-BPTI (4-BPTI), Ser-Ile-Glu-Gly-Arg-BPTI (5-BPTI) and Gly-Ser-Ile-Glu-Gly-Arg-BPTI (6-BPTI) have been studied by 1H n.m.r. The overall structure of the protein is largely unaffected by the addition of extension peptides. pH titration effects on the C-terminal Ala 58 H beta chemical shift indicate that the structure of 1-BPTI at neutral pH is very similar to that of the WT protein, with a salt bridge between the main chain terminal charges. A salt bridge interaction is prevented by addition of the longer extension peptides. Temperature stabilities are measured by high temperature hydrogen isotope exchange and by microcalorimetry. The stability of 1-BPTI is equal to that of WT-BPTI. A slight decrease in stability is observed for longer extensions, following the order WT-BPTI = 1-BPTI < 5-BPTI = 6-BPTI < 4-BPTI. Small changes in chemical shift are observed for 30 invariant resonances in 4-, 5- and 6-BPTI and for a subset of this group in 1-BPTI. These protons are distributed over about half of the BPTI molecule. The size of the chemical shift changes for many resonances follow the same ranking as the temperature stability. The chemical shift effects are attributed to charge and dielectric effects from extension peptides that probably share a common orientation on the surface of BPTI."} {"id": "PMID:1282364", "title": "Interferon alpha therapy in patients with chronic type C hepatitis: changes of serum ALT, anti-HCV & HCV-RNA.", "content": "After the discovery of type C hepatitis virus, the studies on this virus are extensively progressing. The treatment of this viral infection is also widely progressing. Among many agents, recombinant interferon alpha therapy is generally accepted as an effective single agent. To evaluate the efficacy of interferon and to observe the changes of serum aminotransferase (ALT), antibody to hepatitis C virus (anti-HCV) and HCV ribonucleic acid (HCV-RNA), we treated 10 patients with chronic type C hepatitis for 6 months. Patients were randomly divided into 2 groups: 5 patients in group A received interferon and the other 5 in group B received no therapy. Interferon was administered at a dose of 3 million units (MU) daily for the first month and thrice weekly for the following 5 months, and followed up for 2 years. In group A, serum ALT returned to normal in 4: 3, starting at the first month and one at the 3rd month of therapy and maintained normal throughout the follow-up period. In contrast, serum ALT level persistently fluctuated in 4 patients in group B. In one patient, serum ALT returned to normal one and a half years later. Regardless of therapy, serum anti-HCV titer remained unchanged in all patients. However, HCV-RNA, using polymerized chain reaction (PCR), became undetectable in all responded patients and in one untreated patient whose serum ALT returned to normal spontaneously. This study suggested that interferon alpha therapy in patients with chronic type C hepatitis may be clinically effective. Our study also indicated that the detection of HCV-RNA by PCR is useful to predict the prognosis of chronic type C hepatitis.", "contents": "Interferon alpha therapy in patients with chronic type C hepatitis: changes of serum ALT, anti-HCV & HCV-RNA. After the discovery of type C hepatitis virus, the studies on this virus are extensively progressing. The treatment of this viral infection is also widely progressing. Among many agents, recombinant interferon alpha therapy is generally accepted as an effective single agent. To evaluate the efficacy of interferon and to observe the changes of serum aminotransferase (ALT), antibody to hepatitis C virus (anti-HCV) and HCV ribonucleic acid (HCV-RNA), we treated 10 patients with chronic type C hepatitis for 6 months. Patients were randomly divided into 2 groups: 5 patients in group A received interferon and the other 5 in group B received no therapy. Interferon was administered at a dose of 3 million units (MU) daily for the first month and thrice weekly for the following 5 months, and followed up for 2 years. In group A, serum ALT returned to normal in 4: 3, starting at the first month and one at the 3rd month of therapy and maintained normal throughout the follow-up period. In contrast, serum ALT level persistently fluctuated in 4 patients in group B. In one patient, serum ALT returned to normal one and a half years later. Regardless of therapy, serum anti-HCV titer remained unchanged in all patients. However, HCV-RNA, using polymerized chain reaction (PCR), became undetectable in all responded patients and in one untreated patient whose serum ALT returned to normal spontaneously. This study suggested that interferon alpha therapy in patients with chronic type C hepatitis may be clinically effective. Our study also indicated that the detection of HCV-RNA by PCR is useful to predict the prognosis of chronic type C hepatitis."} {"id": "PMID:1282365", "title": "Prevalence of antibodies to hepatitis C virus in patients with various types of liver diseases.", "content": "Hepatitis C virus (HCV) is known to be a major cause of non-A, non-B hepatitis (NANBH) and is thought to be an important causative agent of serious liver disease. Recently the role of HCV in the development of various liver disease is suggested. Sera from 222 patients with various liver diseases had been kept frozen at -20 degrees C until the test. Anti-HCV was detected using the ABBOTT HCV EIA Test System (ABBOTT Co., America) following the manufacturer's instructions. The assay uses a recombinant HCV antigen (C 100-3) synthesized in yeast. HCV antibodies (anti-HCV) were detected in 35 (31.5%) of 111 HBsAg-negative patients. The prevalence rate of anti-HCV was 61.9% (13 out of 21 patients) in chronic hepatitis, 29.1% (14 out of 48) in liver cirrhosis, 26.3% (5 out of 19) in hepatocellular carcinoma and 13% (3 out of 23) in acute hepatitis was far less (3 out of 111 patients, 2. 7%) than that of HBsAg-negative patients (p < 0.01). In this group, anti-HCV was detected in 2 (5.1%) out of 39 liver cirrhosis, 1 (1.9%) out of 52 chronic hepatitis, among them 47 were biopsy-proven chronic active hepatitis, and none of 20 hepatocellular carcinoma. These data suggest that, in Korea, 1) coinfection of HCV and HBV is infrequent, 2) HCV might be an important cause of HBsAg-negative chronic hepatitis, 3) HCV is seemed to be a less likely important factor associated with liver cirrhosis or hepatocellular carcinoma in HBsAg-negative patients, but further prospective study with a large population is necessary.", "contents": "Prevalence of antibodies to hepatitis C virus in patients with various types of liver diseases. Hepatitis C virus (HCV) is known to be a major cause of non-A, non-B hepatitis (NANBH) and is thought to be an important causative agent of serious liver disease. Recently the role of HCV in the development of various liver disease is suggested. Sera from 222 patients with various liver diseases had been kept frozen at -20 degrees C until the test. Anti-HCV was detected using the ABBOTT HCV EIA Test System (ABBOTT Co., America) following the manufacturer's instructions. The assay uses a recombinant HCV antigen (C 100-3) synthesized in yeast. HCV antibodies (anti-HCV) were detected in 35 (31.5%) of 111 HBsAg-negative patients. The prevalence rate of anti-HCV was 61.9% (13 out of 21 patients) in chronic hepatitis, 29.1% (14 out of 48) in liver cirrhosis, 26.3% (5 out of 19) in hepatocellular carcinoma and 13% (3 out of 23) in acute hepatitis was far less (3 out of 111 patients, 2. 7%) than that of HBsAg-negative patients (p < 0.01). In this group, anti-HCV was detected in 2 (5.1%) out of 39 liver cirrhosis, 1 (1.9%) out of 52 chronic hepatitis, among them 47 were biopsy-proven chronic active hepatitis, and none of 20 hepatocellular carcinoma. These data suggest that, in Korea, 1) coinfection of HCV and HBV is infrequent, 2) HCV might be an important cause of HBsAg-negative chronic hepatitis, 3) HCV is seemed to be a less likely important factor associated with liver cirrhosis or hepatocellular carcinoma in HBsAg-negative patients, but further prospective study with a large population is necessary."} {"id": "PMID:1282366", "title": "Meningothelial hamartoma of the scalp. A case report with immunohistochemical studies.", "content": "An unusual and, apparently, hitherto undescribed congenital lesion of the scalp which proved to be heterotopic meningothelial tissue is reported, and its clinical, morphological, and theoretical implications are reviewed. A 14-month-old male infant exhibited a soft tissue lesion on the midline of the parietal scalp since birth. The lesion had grown in size since birth. Histological examination showed an admixture of mature adipose tissue, bands consisting of bundles and small nodules of dense collagen, both enclosed and bordered by rests and strands of meningothelial cells. A network of vessel-like channels lined by plump hyperchromatic cells with spindle-shaped nuclei and occasionally multinucleated giant cells was one of the prominent features. Immunohistochemically, these cells were positive for vimentin, but staining was negative for EMA and all other antibodies tested. A fibrocollagenous stalk via bony defect showed no arachnoid cell rests. The authors believe that the herein described lesion and the hamartoma of the scalp described by Suster and Rosai (1990) may represent varying morphological expressions of a pathogenetically related process. Precautions appropriate to the possibility of intracranial extension must be taken at the time of surgery.", "contents": "Meningothelial hamartoma of the scalp. A case report with immunohistochemical studies. An unusual and, apparently, hitherto undescribed congenital lesion of the scalp which proved to be heterotopic meningothelial tissue is reported, and its clinical, morphological, and theoretical implications are reviewed. A 14-month-old male infant exhibited a soft tissue lesion on the midline of the parietal scalp since birth. The lesion had grown in size since birth. Histological examination showed an admixture of mature adipose tissue, bands consisting of bundles and small nodules of dense collagen, both enclosed and bordered by rests and strands of meningothelial cells. A network of vessel-like channels lined by plump hyperchromatic cells with spindle-shaped nuclei and occasionally multinucleated giant cells was one of the prominent features. Immunohistochemically, these cells were positive for vimentin, but staining was negative for EMA and all other antibodies tested. A fibrocollagenous stalk via bony defect showed no arachnoid cell rests. The authors believe that the herein described lesion and the hamartoma of the scalp described by Suster and Rosai (1990) may represent varying morphological expressions of a pathogenetically related process. Precautions appropriate to the possibility of intracranial extension must be taken at the time of surgery."} {"id": "PMID:1282367", "title": "Cerebrospinal fluid protein variations in common to Alzheimer's disease and schizophrenia.", "content": "Analysis of silver stained two-dimensional (2D) gels of cerebrospinal fluid (CSF) from 27 patients with schizophrenia (SCZ) and 10 patients with Alzheimer's disease (AD) revealed an increase in the relative amount of a polypeptide of 18,000M(r) and isoelectric point of 6.5 when compared to the appropriate controls. This protein was identified by its electrophoretic characteristics and by immune analysis of Western blots as an isoform of alpha-2 haptoglobin, provisionally identified as alpha-2FS haptoglobin. Alzheimer's disease versus control CSF samples showed a 6.8-fold increase in the percent mean density value of this haptoglobin isoform (n = 10 AD vs 11 control; P > 0.025) while a 4.4-fold increase was observed in the schizophrenic patients (n = 17 SCZ vs 10 control; P > 0.001). Two additional polypeptides (proteins '127' and '128') of 40,000 M(r) and isoelectric points 5.7 and 5.9, respectively, described previously by this laboratory, were found in the CSF of 27% of schizophrenics, 23% of the Alzheimer's disease patients, and 4% of the controls in the current study. The presence of proteins 127 and 128, as well as the increased concentrations of alpha-2 haptoglobin in the CSF of Alzheimer's disease and schizophrenic patients, may be useful as diagnostic biological markers. They may also indicate a common pathophysiology between these diseases.", "contents": "Cerebrospinal fluid protein variations in common to Alzheimer's disease and schizophrenia. Analysis of silver stained two-dimensional (2D) gels of cerebrospinal fluid (CSF) from 27 patients with schizophrenia (SCZ) and 10 patients with Alzheimer's disease (AD) revealed an increase in the relative amount of a polypeptide of 18,000M(r) and isoelectric point of 6.5 when compared to the appropriate controls. This protein was identified by its electrophoretic characteristics and by immune analysis of Western blots as an isoform of alpha-2 haptoglobin, provisionally identified as alpha-2FS haptoglobin. Alzheimer's disease versus control CSF samples showed a 6.8-fold increase in the percent mean density value of this haptoglobin isoform (n = 10 AD vs 11 control; P > 0.025) while a 4.4-fold increase was observed in the schizophrenic patients (n = 17 SCZ vs 10 control; P > 0.001). Two additional polypeptides (proteins '127' and '128') of 40,000 M(r) and isoelectric points 5.7 and 5.9, respectively, described previously by this laboratory, were found in the CSF of 27% of schizophrenics, 23% of the Alzheimer's disease patients, and 4% of the controls in the current study. The presence of proteins 127 and 128, as well as the increased concentrations of alpha-2 haptoglobin in the CSF of Alzheimer's disease and schizophrenic patients, may be useful as diagnostic biological markers. They may also indicate a common pathophysiology between these diseases."} {"id": "PMID:1282368", "title": "Comparison of electrophoretic distribution patterns of ribosomal RNA gene restriction fragments and of ribosomal subunit proteins of Lactococci, Streptococci, and Pediococci.", "content": "Comparison of electrophoretic distribution patterns of ribosomal RNA gene restriction fragments and of ribosomal subunit proteins are equally effective procedures for detecting differences and similarities in the Lactococci, Streptococci and Pediococci examined. Electrophoretic distribution patterns of ribosomal subunit proteins may be a useful tool in taxonomic studies.", "contents": "Comparison of electrophoretic distribution patterns of ribosomal RNA gene restriction fragments and of ribosomal subunit proteins of Lactococci, Streptococci, and Pediococci. Comparison of electrophoretic distribution patterns of ribosomal RNA gene restriction fragments and of ribosomal subunit proteins are equally effective procedures for detecting differences and similarities in the Lactococci, Streptococci and Pediococci examined. Electrophoretic distribution patterns of ribosomal subunit proteins may be a useful tool in taxonomic studies."} {"id": "PMID:1282369", "title": "Serum total amylase activity and its isoenzyme fractions in newborn pigs with relation to growth and iron dextran-treatment.", "content": "Serum amylase activity was analyzed chromogenically (blue starch method) and its isoenzyme was separated by cellulose acetate membrane electrophoresis in newborn pigs comparing with those in adult pigs. Serum amylase activity in newborn pigs was about one half of adults' and increased with age. Serum amylase isoenzymes were separated into 4 fractions from the cathode. The isoenzymes were also classified in 5 types on the basis of the combination of these 4 fractions. Incidences of the fractions and the types were not significantly different between adults and newborns. After the iron dextran treatment, serum amylase activity as well as levels of erythrocytes, hemoglobin and packed cell volume increased. The rates of increase in hemoglobin and packed cell volume were more significant in the double treatment group than in the single treatment group, while serum amylase activity increased similarly in these 2 groups. The increase in serum amylase activity seemed to indicate that the development of amylase-producing organs was reinforced by the iron compound treatment. It is thought that serum amylase activity may be an indicator of healthy growth in newborn pigs.", "contents": "Serum total amylase activity and its isoenzyme fractions in newborn pigs with relation to growth and iron dextran-treatment. Serum amylase activity was analyzed chromogenically (blue starch method) and its isoenzyme was separated by cellulose acetate membrane electrophoresis in newborn pigs comparing with those in adult pigs. Serum amylase activity in newborn pigs was about one half of adults' and increased with age. Serum amylase isoenzymes were separated into 4 fractions from the cathode. The isoenzymes were also classified in 5 types on the basis of the combination of these 4 fractions. Incidences of the fractions and the types were not significantly different between adults and newborns. After the iron dextran treatment, serum amylase activity as well as levels of erythrocytes, hemoglobin and packed cell volume increased. The rates of increase in hemoglobin and packed cell volume were more significant in the double treatment group than in the single treatment group, while serum amylase activity increased similarly in these 2 groups. The increase in serum amylase activity seemed to indicate that the development of amylase-producing organs was reinforced by the iron compound treatment. It is thought that serum amylase activity may be an indicator of healthy growth in newborn pigs."} {"id": "PMID:1282370", "title": "Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings.", "content": "The syndrome of chronic fatigue, feverishness, diffuse pains, and other constitutional complaints, often precipitated by an acute infectious illness and aggravated by physical and emotional stressors, has a lengthy history in the medical literature. The Centers for Disease Control (CDC) recently formulated a case definition, renaming the illness \"chronic fatigue syndrome.\" Nevertheless, there remain few biological data that can validate the existence of this syndrome as distinct from a wide variety of other, largely psychiatric disorders, and little understanding of its pathogenesis. In the present study, basal plasma and cerebrospinal fluid levels of the monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were determined in 19 patients meeting CDC research case criteria for chronic fatigue syndrome and in 17 normal individuals. Patients with chronic fatigue syndrome showed a significant reduction in basal plasma levels of MHPG and a significant increase in basal plasma levels of 5-HIAA. Although the functional significance of these findings has not been definitively elucidated, they are compatible with the clinical presentation of a syndrome associated with chronic lethargy and fatigue, and with evidence of persistent immune stimulation, and lend support to the idea that chronic fatigue syndrome represents a clinical entity with potential biological specificity.", "contents": "Plasma and cerebrospinal fluid monoamine metabolism in patients with chronic fatigue syndrome: preliminary findings. The syndrome of chronic fatigue, feverishness, diffuse pains, and other constitutional complaints, often precipitated by an acute infectious illness and aggravated by physical and emotional stressors, has a lengthy history in the medical literature. The Centers for Disease Control (CDC) recently formulated a case definition, renaming the illness \"chronic fatigue syndrome.\" Nevertheless, there remain few biological data that can validate the existence of this syndrome as distinct from a wide variety of other, largely psychiatric disorders, and little understanding of its pathogenesis. In the present study, basal plasma and cerebrospinal fluid levels of the monoamine metabolites, 3-methoxy-4-hydroxyphenylglycol (MHPG), 5-hydroxyindoleacetic acid (5-HIAA), and homovanillic acid (HVA) were determined in 19 patients meeting CDC research case criteria for chronic fatigue syndrome and in 17 normal individuals. Patients with chronic fatigue syndrome showed a significant reduction in basal plasma levels of MHPG and a significant increase in basal plasma levels of 5-HIAA. Although the functional significance of these findings has not been definitively elucidated, they are compatible with the clinical presentation of a syndrome associated with chronic lethargy and fatigue, and with evidence of persistent immune stimulation, and lend support to the idea that chronic fatigue syndrome represents a clinical entity with potential biological specificity."} {"id": "PMID:1282371", "title": "Growth and microvascular development of the uterus during early pregnancy in ewes.", "content": "Growth and microvascular development of the uterus were evaluated for ewes on Days 12, 18, 24, and 30 after mating (3-4 ewes/day; Day 0 = day of mating) in two experiments. In experiment 1, fresh weight and dry weight of gravid uterine horns were increased on Days 24 and 30 after mating, whereas those of nongravid uterine horns were elevated only on Day 30. The increased fresh and dry weights of gravid uterine horns on Day 24 were associated with uterine hyperplasia (increased DNA content). Increased fresh and dry weights of gravid uterine horns on Day 30, however, were associated with hypertrophy (increased RNA:DNA and protein:DNA ratios) of uterine tissues. In experiment 2, vascularity of endometrial tissues was elevated on Days 24 and 30 after mating. In addition, dramatic changes in uterine architecture (increased lumenal diameter and decreased endometrial thickness) and in uterine microvascular development (increased abundance of large microvessels and development of a subepithelial capillary plexus) were observed by Day 24 after mating. Characterization of the patterns of uterine growth and microvascular development will enable us to further define the role of previously reported uterine and conceptus-derived growth and angiogenic factors during early pregnancy.", "contents": "Growth and microvascular development of the uterus during early pregnancy in ewes. Growth and microvascular development of the uterus were evaluated for ewes on Days 12, 18, 24, and 30 after mating (3-4 ewes/day; Day 0 = day of mating) in two experiments. In experiment 1, fresh weight and dry weight of gravid uterine horns were increased on Days 24 and 30 after mating, whereas those of nongravid uterine horns were elevated only on Day 30. The increased fresh and dry weights of gravid uterine horns on Day 24 were associated with uterine hyperplasia (increased DNA content). Increased fresh and dry weights of gravid uterine horns on Day 30, however, were associated with hypertrophy (increased RNA:DNA and protein:DNA ratios) of uterine tissues. In experiment 2, vascularity of endometrial tissues was elevated on Days 24 and 30 after mating. In addition, dramatic changes in uterine architecture (increased lumenal diameter and decreased endometrial thickness) and in uterine microvascular development (increased abundance of large microvessels and development of a subepithelial capillary plexus) were observed by Day 24 after mating. Characterization of the patterns of uterine growth and microvascular development will enable us to further define the role of previously reported uterine and conceptus-derived growth and angiogenic factors during early pregnancy."} {"id": "PMID:1282372", "title": "Postnatal development of sympathetic and sensory innervation of the rhesus monkey ovary.", "content": "We have used immunofluorescence to study the postnatal development of the sympathetic and sensory innervation to the rhesus monkey (Macaca mulatta) ovary. Sympathetic nerves were identified as adrenergic by their content of tyrosine hydroxylase (TH)-like immunoreactivity and as peptidergic by the presence of neuropeptide Y (NPY). Fibers containing substance P (SP) or calcitonin gene-related peptide (CGRP)-like immunoreactivity were considered as sensory, whereas vasoactive intestinal peptide (VIP)-positive fibers were only defined as peptidergic because VIP may be present in both sympathetic and sensory nerves. Ovaries from neonatal (2-mo-old), juvenile (9-18-mo-old), peripubertal (3-3.5-yr-old), adult (9-14-yr-old), and senescent (20-27-yr-old) monkeys were studied. At all ages, with the exception of senescence, TH-, NPY-, and VIP-containing fibers were associated with follicles in different developmental stages. In peripubertal and adult animals, some primordial follicles were found to be selectively innervated by VIPergic fibers that almost completely encircled each follicle. Both sympathetic and VIP fibers were also detected in the interstitial tissue and associated with the ovarian vasculature at all ages. The number of sympathetic and VIP fibers increased significantly (p < 0.01) between 2 mo and 9-18 mo of age, and again increased (p < 0.01) around the age of puberty (approximately 3 yr of age). After this time, the number of NPY and TH fibers remained constant. Conversely, the number of VIP fibers decreased (p < 0.05) by 9-14 yr of age, but remained constant thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Postnatal development of sympathetic and sensory innervation of the rhesus monkey ovary. We have used immunofluorescence to study the postnatal development of the sympathetic and sensory innervation to the rhesus monkey (Macaca mulatta) ovary. Sympathetic nerves were identified as adrenergic by their content of tyrosine hydroxylase (TH)-like immunoreactivity and as peptidergic by the presence of neuropeptide Y (NPY). Fibers containing substance P (SP) or calcitonin gene-related peptide (CGRP)-like immunoreactivity were considered as sensory, whereas vasoactive intestinal peptide (VIP)-positive fibers were only defined as peptidergic because VIP may be present in both sympathetic and sensory nerves. Ovaries from neonatal (2-mo-old), juvenile (9-18-mo-old), peripubertal (3-3.5-yr-old), adult (9-14-yr-old), and senescent (20-27-yr-old) monkeys were studied. At all ages, with the exception of senescence, TH-, NPY-, and VIP-containing fibers were associated with follicles in different developmental stages. In peripubertal and adult animals, some primordial follicles were found to be selectively innervated by VIPergic fibers that almost completely encircled each follicle. Both sympathetic and VIP fibers were also detected in the interstitial tissue and associated with the ovarian vasculature at all ages. The number of sympathetic and VIP fibers increased significantly (p < 0.01) between 2 mo and 9-18 mo of age, and again increased (p < 0.01) around the age of puberty (approximately 3 yr of age). After this time, the number of NPY and TH fibers remained constant. Conversely, the number of VIP fibers decreased (p < 0.05) by 9-14 yr of age, but remained constant thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282373", "title": "Androgens are necessary for the establishment of secretory protein expression in the guinea pig seminal vesicle epithelium.", "content": "The guinea pig seminal vesicle epithelium (GPSVE) synthesizes and secretes milligram quantities of four related secretory proteins in an androgen-dependent manner. To investigate the role of androgens in the establishment of secretory protein synthesis during the development of the GPSVE, animals were castrated at Day 5, approximately 10 days before secretory protein accumulation begins in intact animals. Castration did not eliminate secretory protein mRNA from the SVE, but it did indefinitely postpone the developmentally programmed increase in secretory protein mRNA. Injection of neonatally castrated guinea pigs with either estradiol or dexamethasone did not alter levels of secretory protein mRNAs. However, treatment of castrated neonates with either testosterone propionate or dihydrotestosterone (DHT) led to specific increases in secretory protein mRNAs within 4 days. Although neonatally castrated animals accumulated and translated significant amounts of secretory protein mRNA, the newly synthesized secretory proteins failed to accumulate until exogenous androgens were provided. This observation suggests that androgens regulate both the accumulation of secretory protein mRNA and the accumulation of secretory proteins in the GPSVE.", "contents": "Androgens are necessary for the establishment of secretory protein expression in the guinea pig seminal vesicle epithelium. The guinea pig seminal vesicle epithelium (GPSVE) synthesizes and secretes milligram quantities of four related secretory proteins in an androgen-dependent manner. To investigate the role of androgens in the establishment of secretory protein synthesis during the development of the GPSVE, animals were castrated at Day 5, approximately 10 days before secretory protein accumulation begins in intact animals. Castration did not eliminate secretory protein mRNA from the SVE, but it did indefinitely postpone the developmentally programmed increase in secretory protein mRNA. Injection of neonatally castrated guinea pigs with either estradiol or dexamethasone did not alter levels of secretory protein mRNAs. However, treatment of castrated neonates with either testosterone propionate or dihydrotestosterone (DHT) led to specific increases in secretory protein mRNAs within 4 days. Although neonatally castrated animals accumulated and translated significant amounts of secretory protein mRNA, the newly synthesized secretory proteins failed to accumulate until exogenous androgens were provided. This observation suggests that androgens regulate both the accumulation of secretory protein mRNA and the accumulation of secretory proteins in the GPSVE."} {"id": "PMID:1282374", "title": "Electroporation and electrophoretic DNA transfer into cells. The effect of DNA interaction with electropores.", "content": "It has been shown recently that electrically induced DNA transfer into cells is a fast vectorial process with the same direction as DNA electrophoresis in an external electric field (Klenchin, V. A., S. I. Sukharev, S. M. Serov, L. V. Chernomordik, and Y. A. Chizmadzhev. 1991. Biophys. J. 60:804-811). Here we describe the effect of DNA interaction with membrane electropores and provide additional evidences for the key role of DNA electrophoresis in cell electrotransfection. The assay of electrically induced uptake of fluorescent dextrans (FDs) by cells shows that the presence of DNA in the medium during electroporation leads to a sharp increase in membrane permeability to FDs of M(r) < 20,000. The permeability increases with DNA concentration and the effect is seen even if FD is added to the cell suspension a few minutes after pulse application. The longer the DNA fragment, the greater the increase in permeability. The use of a two-pulse technique allows us to separate two effects provided by a pulsed electric field: membrane electroporation and DNA electrophoresis. The first pulse (6 kV/cm, 10 microseconds) creates pores efficiently, whereas transfection efficiency (TE) is low. The second pulse of much lower amplitude, but substantially longer (0.2 kV/cm, 10 ms), does not cause poration and transfection by itself but enhances TE by about one order of magnitude. In two-pulse experiments, TE rises monotonously with the increase of the second pulse duration. By varying the delay duration between the two pulses, we estimate the lifetime of electropores (which are DNA-permeable in conditions of low electric field) as tens of seconds. The data suggest that the mechanism of cell electrotransfection is underlain by electrophoretic movement of DNA through membrane pores, the size of which is determined by interaction with DNA in an electric field.", "contents": "Electroporation and electrophoretic DNA transfer into cells. The effect of DNA interaction with electropores. It has been shown recently that electrically induced DNA transfer into cells is a fast vectorial process with the same direction as DNA electrophoresis in an external electric field (Klenchin, V. A., S. I. Sukharev, S. M. Serov, L. V. Chernomordik, and Y. A. Chizmadzhev. 1991. Biophys. J. 60:804-811). Here we describe the effect of DNA interaction with membrane electropores and provide additional evidences for the key role of DNA electrophoresis in cell electrotransfection. The assay of electrically induced uptake of fluorescent dextrans (FDs) by cells shows that the presence of DNA in the medium during electroporation leads to a sharp increase in membrane permeability to FDs of M(r) < 20,000. The permeability increases with DNA concentration and the effect is seen even if FD is added to the cell suspension a few minutes after pulse application. The longer the DNA fragment, the greater the increase in permeability. The use of a two-pulse technique allows us to separate two effects provided by a pulsed electric field: membrane electroporation and DNA electrophoresis. The first pulse (6 kV/cm, 10 microseconds) creates pores efficiently, whereas transfection efficiency (TE) is low. The second pulse of much lower amplitude, but substantially longer (0.2 kV/cm, 10 ms), does not cause poration and transfection by itself but enhances TE by about one order of magnitude. In two-pulse experiments, TE rises monotonously with the increase of the second pulse duration. By varying the delay duration between the two pulses, we estimate the lifetime of electropores (which are DNA-permeable in conditions of low electric field) as tens of seconds. The data suggest that the mechanism of cell electrotransfection is underlain by electrophoretic movement of DNA through membrane pores, the size of which is determined by interaction with DNA in an electric field."} {"id": "PMID:1282375", "title": "The beta subunit controls the gating and dihydropyridine sensitivity of the skeletal muscle Ca2+ channel.", "content": "The skeletal muscle (SKM) L-type Ca2+ channel is composed of a central subunit designated alpha 1, which contains the pore and the dihydropyridine (DHP) binding domains and three associated subunits, alpha 2/delta, beta, and gamma, which influence the activity of the SKM alpha 1. Coexpression of SKM alpha 1 and SKM beta in stably transfected mouse L cells results in a dramatic increase in DHP binding accompanied by fast gated Ba2+ currents. We report here that this \"SKM alpha 1 beta-related phenotype\" can be converted upon intracellular trypsin treatment into a slowly inactivating, DHP sensitive \"SKM alpha 1 phenotype.\" These observations indicate that current amplitude, fast inactivation, and DHP sensitivity are modulated by an interaction of SKM alpha 1 and SKM beta on the internal side of the membrane.", "contents": "The beta subunit controls the gating and dihydropyridine sensitivity of the skeletal muscle Ca2+ channel. The skeletal muscle (SKM) L-type Ca2+ channel is composed of a central subunit designated alpha 1, which contains the pore and the dihydropyridine (DHP) binding domains and three associated subunits, alpha 2/delta, beta, and gamma, which influence the activity of the SKM alpha 1. Coexpression of SKM alpha 1 and SKM beta in stably transfected mouse L cells results in a dramatic increase in DHP binding accompanied by fast gated Ba2+ currents. We report here that this \"SKM alpha 1 beta-related phenotype\" can be converted upon intracellular trypsin treatment into a slowly inactivating, DHP sensitive \"SKM alpha 1 phenotype.\" These observations indicate that current amplitude, fast inactivation, and DHP sensitivity are modulated by an interaction of SKM alpha 1 and SKM beta on the internal side of the membrane."} {"id": "PMID:1282376", "title": "Mitochondrial ATP synthase regulation in heart: defects in hypertension are restored after treatment with captopril.", "content": "Control of mitochondrial ATP synthase capacity was investigated in cultured cardiomyocytes from normotensive (Wistar-Kyoto) and spontaneously hypertensive rats. Cells from spontaneously hypertensive rats have a higher basal ATP synthase capacity than those from normotensives, but lack the normal up-regulation in response to an increased energy demand. After treatment of spontaneously hypertensive rats with captopril (60 mg/kg per day for 12 weeks), cellular hypertrophy characteristic of the hypertensives was abolished and the cardiomyocytes showed a normal ATP synthase capacity. Normal up-regulation of this enzyme was also restored. All cells showed a normal down-regulation of the synthase in response to cyanide. Experiments with the calcium antagonists, verapamil and ruthenium red, suggest that abnormal ATP synthase regulation observed in the untreated spontaneously hypertensive rats results from an alteration of Ca2+ handling in cardiac cells under chronic high workload, which is reversed by captopril treatment.", "contents": "Mitochondrial ATP synthase regulation in heart: defects in hypertension are restored after treatment with captopril. Control of mitochondrial ATP synthase capacity was investigated in cultured cardiomyocytes from normotensive (Wistar-Kyoto) and spontaneously hypertensive rats. Cells from spontaneously hypertensive rats have a higher basal ATP synthase capacity than those from normotensives, but lack the normal up-regulation in response to an increased energy demand. After treatment of spontaneously hypertensive rats with captopril (60 mg/kg per day for 12 weeks), cellular hypertrophy characteristic of the hypertensives was abolished and the cardiomyocytes showed a normal ATP synthase capacity. Normal up-regulation of this enzyme was also restored. All cells showed a normal down-regulation of the synthase in response to cyanide. Experiments with the calcium antagonists, verapamil and ruthenium red, suggest that abnormal ATP synthase regulation observed in the untreated spontaneously hypertensive rats results from an alteration of Ca2+ handling in cardiac cells under chronic high workload, which is reversed by captopril treatment."} {"id": "PMID:1282377", "title": "Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret.", "content": "The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Cyclic GMP inhibits the inotropic response to alpha 1-adrenoceptors in the papillary muscle of the ferret. The physiological role of cyclic GMP in the heart remains controversial. In the present study we investigated the interaction between a number of agents known to increase the level of cyclic GMP in the myocardium and alpha 1-adrenergic stimulation in isolated preparations of cardiac papillary muscle in the ferret. Inotropic responses to the cumulative addition of phenylephrine were measured in papillary muscles of the ferret in the absence and presence of 1 microM sodium nitroprusside, 1 microM atrial natriuretic peptide, 0.1 microM substance P (which stimulates the release of nitric oxide from endocardial endothelium) or 1 microM 8-bromo-cyclic GMP. In parallel experiments using similar preparations, alpha 1-induced hydrolysis of phosphatidylinositol was assessed by measuring changes in the levels of inositol 1,4,5-trisphosphate in response to 10 microM phenylephrine in the absence and presence of the same agents that increase the level of cyclic GMP. Phenylephrine (0.001-10 microM) induced a concentration-dependent positive inotropic effect that was significantly inhibited by each of the agents that increase cyclic GMP. Phenylephrine (10 microM) induced an approximately three-fold rise in the level of inositol trisphosphate in the myocardium, which was likewise significantly inhibited by each of the agents that increase cyclic GMP. These data show that agents that increase the level of cyclic GMP in the myocardium inhibit both the positive inotropic and phosphatidylinositol response to alpha 1-stimulation in isolated preparations of papillary muscle in the ferret.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282378", "title": "Intercellular adhesion molecules and vascular cell adhesion molecule-1 and the kidney.", "content": "Adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are expressed in the kidney and are regulated by proinflammatory cytokines. These adhesion molecules play an important role in the binding and activation process of leukocytes and are of importance in inflammatory kidney diseases. This review article describes current knowledge regarding the structure, expression, and functional role of adhesion molecules and their significance in immune-mediated renal diseases.", "contents": "Intercellular adhesion molecules and vascular cell adhesion molecule-1 and the kidney. Adhesion molecules such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 are expressed in the kidney and are regulated by proinflammatory cytokines. These adhesion molecules play an important role in the binding and activation process of leukocytes and are of importance in inflammatory kidney diseases. This review article describes current knowledge regarding the structure, expression, and functional role of adhesion molecules and their significance in immune-mediated renal diseases."} {"id": "PMID:1282379", "title": "Analysis of leukemic cell activity with a simple acridine orange staining method.", "content": "Leukemic cells from 28 patients with acute lymphoblastic leukemia (ALL) were supravitally stained with acridine orange (AO). Based on the staining characteristics of their cells, the patients were divided into an orange cell-dominant group (15 patients) and a green cell-dominant group (13 patients). The prognosis was better in the former than in the latter group. Orange cells which had high RNA contents were observed, while the proportion of dividing cells was high. Supravital staining with AO is a very simple and useful method for assessing the metabolic activity of leukemic cells in ALL; this method may thus be useful in assessing the prognosis of these patients.", "contents": "Analysis of leukemic cell activity with a simple acridine orange staining method. Leukemic cells from 28 patients with acute lymphoblastic leukemia (ALL) were supravitally stained with acridine orange (AO). Based on the staining characteristics of their cells, the patients were divided into an orange cell-dominant group (15 patients) and a green cell-dominant group (13 patients). The prognosis was better in the former than in the latter group. Orange cells which had high RNA contents were observed, while the proportion of dividing cells was high. Supravital staining with AO is a very simple and useful method for assessing the metabolic activity of leukemic cells in ALL; this method may thus be useful in assessing the prognosis of these patients."} {"id": "PMID:1282380", "title": "Cellular localization of IGF-I and IGF-II mRNAs in immature hypophysectomized rat testis and epididymis after in vivo hormonal treatment.", "content": "IGF-I and II genes expression has been localized by in situ hybridization in testis and epididymis of immature hypophysectomized rats treated in vivo with either pFSH, hLH, bGH, hPRL or with saline. IGF-I mRNA expression was found in both Sertoli and Leydig cells after treatment with either FSH or LH. IGF-I mRNA was highly expressed in germ cells after FSH stimulation and to a lesser extent after GH or LH treatments. However, its expression was very low in hypophysectomized control or PRL treated rats. IGF-I mRNA was also expressed in stromal cells of epididymis after LH treatment and to a lesser extent after GH stimulation. In contrast, IGF-II mRNA expression was detected in all testicular cell types whatever the hormonal treatment (FSH, LH, GH, PRL). For each hormonal treatment testicular sections were examined after immunohistochemical staining with specific antisera against IGF-I and IGF-II. Both in situ hybridization and immunohistochemical data were examined in order to determine the testicular sites of synthesis of IGF-I and IGF-II.", "contents": "Cellular localization of IGF-I and IGF-II mRNAs in immature hypophysectomized rat testis and epididymis after in vivo hormonal treatment. IGF-I and II genes expression has been localized by in situ hybridization in testis and epididymis of immature hypophysectomized rats treated in vivo with either pFSH, hLH, bGH, hPRL or with saline. IGF-I mRNA expression was found in both Sertoli and Leydig cells after treatment with either FSH or LH. IGF-I mRNA was highly expressed in germ cells after FSH stimulation and to a lesser extent after GH or LH treatments. However, its expression was very low in hypophysectomized control or PRL treated rats. IGF-I mRNA was also expressed in stromal cells of epididymis after LH treatment and to a lesser extent after GH stimulation. In contrast, IGF-II mRNA expression was detected in all testicular cell types whatever the hormonal treatment (FSH, LH, GH, PRL). For each hormonal treatment testicular sections were examined after immunohistochemical staining with specific antisera against IGF-I and IGF-II. Both in situ hybridization and immunohistochemical data were examined in order to determine the testicular sites of synthesis of IGF-I and IGF-II."} {"id": "PMID:1282381", "title": "Erucic acid metabolism in rat liver. A combined biochemical and radioautographical study.", "content": "Metabolism of erucic acid was studied in rat liver in comparison with oleic acid in relation with diet lipids. Rats were fed for 3 or 60 days a balanced diet containing 30% of the calories of either rapeseed oil rich in erucic acid or sunflower seed oil rich in linoleic acid. They were intravenously injected with tritiated erucic or oleic acid. After 1 or 15 min, the radioactivity recovered in liver lipids was 9 to 26% whatever the diet or the acid injected. One minute after injection of erucic acid a high part of radioactivity was recovered in the free fatty acid fraction and as untransformed erucic acid. After 15 min the major part of radioactivity was recovered in the triacylglycerol fraction which contained a high proportion of labelled oleic acid formed by shortening of erucic acid. The autoradiography did not show any marked difference between the labelling of peroxisomes and mitochondria when tritiated erucic or oleic acid was injected. These data do not bring about arguments for a peroxisomal nor for a mitochondrial location of erucic acid shortening in liver.", "contents": "Erucic acid metabolism in rat liver. A combined biochemical and radioautographical study. Metabolism of erucic acid was studied in rat liver in comparison with oleic acid in relation with diet lipids. Rats were fed for 3 or 60 days a balanced diet containing 30% of the calories of either rapeseed oil rich in erucic acid or sunflower seed oil rich in linoleic acid. They were intravenously injected with tritiated erucic or oleic acid. After 1 or 15 min, the radioactivity recovered in liver lipids was 9 to 26% whatever the diet or the acid injected. One minute after injection of erucic acid a high part of radioactivity was recovered in the free fatty acid fraction and as untransformed erucic acid. After 15 min the major part of radioactivity was recovered in the triacylglycerol fraction which contained a high proportion of labelled oleic acid formed by shortening of erucic acid. The autoradiography did not show any marked difference between the labelling of peroxisomes and mitochondria when tritiated erucic or oleic acid was injected. These data do not bring about arguments for a peroxisomal nor for a mitochondrial location of erucic acid shortening in liver."} {"id": "PMID:1282382", "title": "Long-term effects of dietary monounsaturated and polyunsaturated fatty acids on plasma lipids in dogs.", "content": "To compare the effect of monounsaturated vs. polyunsaturated fatty acids on plasma lipids, three months old dogs were studied for a period of six months. The dogs were fed a basal diet supplemented with either 14% olive oil or sunflower oil. Blood samples were taken fortnightly during this period. We have found changes in the various unsaturated fatty acids in response to the diet. Oleic and 20:3 n-9 acids were higher in the olive oil group while linoleic acid was increased in the dogs fed the sunflower oil diet. Arachidonic acid and PUFA n-3 > 18C index were nearly similar with both diets. The cholesterol levels were similar to those found in adult humans and no significant differences were brought about diets at any time. Thus a diet rich in monounsaturated fatty acids is as efficient as a polyunsaturated rich in relation to total cholesterol levels but more beneficial because of the antiatherogenic effect of HDL-cholesterol which is increased with this type of dietary fat.", "contents": "Long-term effects of dietary monounsaturated and polyunsaturated fatty acids on plasma lipids in dogs. To compare the effect of monounsaturated vs. polyunsaturated fatty acids on plasma lipids, three months old dogs were studied for a period of six months. The dogs were fed a basal diet supplemented with either 14% olive oil or sunflower oil. Blood samples were taken fortnightly during this period. We have found changes in the various unsaturated fatty acids in response to the diet. Oleic and 20:3 n-9 acids were higher in the olive oil group while linoleic acid was increased in the dogs fed the sunflower oil diet. Arachidonic acid and PUFA n-3 > 18C index were nearly similar with both diets. The cholesterol levels were similar to those found in adult humans and no significant differences were brought about diets at any time. Thus a diet rich in monounsaturated fatty acids is as efficient as a polyunsaturated rich in relation to total cholesterol levels but more beneficial because of the antiatherogenic effect of HDL-cholesterol which is increased with this type of dietary fat."} {"id": "PMID:1282383", "title": "Reproductive function in female rats submitted to chronic hypobaric hypoxia.", "content": "Female rats were submitted to 5,500 m simulated altitude (50.7 kPa) for 23 weeks in a hypobaric chamber. In vitro biosynthesis of estradiol from labelled pregnenolone was studied in the ovaries of these rats and of their controls at sea level barometric pressure. The weight of the ovaries expressed as mg/rat was 63% higher (p < 0.001) and estradiol biosynthetic capacity expressed as % conversion/rat was 140% higher (p < 0.01) in hypoxic than in control rats. Estrous cycle and fertility were studied in rats submitted to 4,400 m simulated altitude (58.6 kPa) and in their controls. The percentage of estrous was significantly higher in hypoxic than in control animals. The fertility was lower in hypoxic rats. Optical microscopy showed signs of polycystic ovaries in both hypoxic groups. These results may suggest that the normal reproductive function includes oxygen dependent factors.", "contents": "Reproductive function in female rats submitted to chronic hypobaric hypoxia. Female rats were submitted to 5,500 m simulated altitude (50.7 kPa) for 23 weeks in a hypobaric chamber. In vitro biosynthesis of estradiol from labelled pregnenolone was studied in the ovaries of these rats and of their controls at sea level barometric pressure. The weight of the ovaries expressed as mg/rat was 63% higher (p < 0.001) and estradiol biosynthetic capacity expressed as % conversion/rat was 140% higher (p < 0.01) in hypoxic than in control rats. Estrous cycle and fertility were studied in rats submitted to 4,400 m simulated altitude (58.6 kPa) and in their controls. The percentage of estrous was significantly higher in hypoxic than in control animals. The fertility was lower in hypoxic rats. Optical microscopy showed signs of polycystic ovaries in both hypoxic groups. These results may suggest that the normal reproductive function includes oxygen dependent factors."} {"id": "PMID:1282384", "title": "Brain acetylcholinesterase activity and optomotor behavior in bluegills, Lepomis macrochirus exposed to different concentrations of diazinon.", "content": "Organophosphorus pesticides inhibit acetylcholinesterase (AChE) activity to varying degrees in different species of fish. Estimation of AChE activity is a useful tool for establishing the degree of pollution caused by these pesticides. Behavioral changes are very good and sensitive indicators of any chemical pollution. Changes in the optomotor behavior are easily quantifiable. Therefore estimation of AChE activity and changes in the optomotor response are taken as criteria to study the effects of different concentrations (15, 30, 45, 60 and 75 micrograms/l) of diazinon, an organophosphorus compound, in bluegill Sunfish, Lepomis macrochirus. The fish were exposed for a period of 24 hours. In this study, AChE activity showed a significant decline above an exposure concentration of 45 micrograms/l exposure concentration. In the case of optomotor behavior, a decline in the scores of the \"following\" responses of the fish was noticed from an exposure concentration of 30 micrograms/l. It seems that a behavioral bioassay is more sensitive than other types of testing.", "contents": "Brain acetylcholinesterase activity and optomotor behavior in bluegills, Lepomis macrochirus exposed to different concentrations of diazinon. Organophosphorus pesticides inhibit acetylcholinesterase (AChE) activity to varying degrees in different species of fish. Estimation of AChE activity is a useful tool for establishing the degree of pollution caused by these pesticides. Behavioral changes are very good and sensitive indicators of any chemical pollution. Changes in the optomotor behavior are easily quantifiable. Therefore estimation of AChE activity and changes in the optomotor response are taken as criteria to study the effects of different concentrations (15, 30, 45, 60 and 75 micrograms/l) of diazinon, an organophosphorus compound, in bluegill Sunfish, Lepomis macrochirus. The fish were exposed for a period of 24 hours. In this study, AChE activity showed a significant decline above an exposure concentration of 45 micrograms/l exposure concentration. In the case of optomotor behavior, a decline in the scores of the \"following\" responses of the fish was noticed from an exposure concentration of 30 micrograms/l. It seems that a behavioral bioassay is more sensitive than other types of testing."} {"id": "PMID:1282385", "title": "Effects of inhalation of ethyl-ether on glycemia and on some variables of intermediate metabolism in rats.", "content": "The influence of a anesthetic, ethyl-ether, on arterial plasma levels of glucose, insulin and lipids was studied in starved Wistar rats. Ethyl-ether increased significantly (P < 0.05) glucose plasma levels, as a result not only of stress and of the release of catecholamines and glucocorticoids, but also of the decrease in the use of glucose by the tissues. Ethyl-ether did not change significantly the level of triglycerides, cholesterol and phospholipids. Insulin concentration was not increased, even when hyperglycemia was established. Ketonuria, acidosis and hypercapnia were increased. In these rats the administration of insulin produced a diminution in glycemia. The findings suggest that, under anesthesia with ether, the endocrine pancreas is incapable of recognizing glucose as a specific stimulus to promote the release of insulin.", "contents": "Effects of inhalation of ethyl-ether on glycemia and on some variables of intermediate metabolism in rats. The influence of a anesthetic, ethyl-ether, on arterial plasma levels of glucose, insulin and lipids was studied in starved Wistar rats. Ethyl-ether increased significantly (P < 0.05) glucose plasma levels, as a result not only of stress and of the release of catecholamines and glucocorticoids, but also of the decrease in the use of glucose by the tissues. Ethyl-ether did not change significantly the level of triglycerides, cholesterol and phospholipids. Insulin concentration was not increased, even when hyperglycemia was established. Ketonuria, acidosis and hypercapnia were increased. In these rats the administration of insulin produced a diminution in glycemia. The findings suggest that, under anesthesia with ether, the endocrine pancreas is incapable of recognizing glucose as a specific stimulus to promote the release of insulin."} {"id": "PMID:1282387", "title": "Factors simultaneously affecting the growth of the rainbow trout (Oncorhynchus mykiss).", "content": "Growth of rainbow trout (Oncorhynchus mykiss) is examined in relation to simultaneous variation of initial weight, initial density, temperature and time (days). Twenty-six lots of medium weight were set up, ranging from 92 to 372 g; initial density ranged from 7.2 to 38.8 kg/m3; and temperatures from 14 degrees C in winter to 20 degrees well into spring. Experimental periods carried out were of 7, 20, 38 and 26 days duration. By multiple correlation and regression analysis, predictive equations for increments in weight, final density were obtained in relation to the afore mentioned variables and ranges. The values of multiple correlation obtained were highly significant. We confirmed that the effect of each factor on growth is modified by the simultaneous action of the other variables.", "contents": "Factors simultaneously affecting the growth of the rainbow trout (Oncorhynchus mykiss). Growth of rainbow trout (Oncorhynchus mykiss) is examined in relation to simultaneous variation of initial weight, initial density, temperature and time (days). Twenty-six lots of medium weight were set up, ranging from 92 to 372 g; initial density ranged from 7.2 to 38.8 kg/m3; and temperatures from 14 degrees C in winter to 20 degrees well into spring. Experimental periods carried out were of 7, 20, 38 and 26 days duration. By multiple correlation and regression analysis, predictive equations for increments in weight, final density were obtained in relation to the afore mentioned variables and ranges. The values of multiple correlation obtained were highly significant. We confirmed that the effect of each factor on growth is modified by the simultaneous action of the other variables."} {"id": "PMID:1282386", "title": "Endocrine and hemodynamic responses to dopamine infusion in the guinea-pig: effects of ACE inhibition with perindopril.", "content": "The effects of dopamine on plasma renin-angiotensin-aldosterone system vasopressin levels and blood pressure were studied in anesthetized guinea-pig. The inhibition of the angiotensin converting enzyme with perindopril permitted assessment of the role of the renin-angiotensin system. In perindopril-treated guinea-pigs, the activity of angiotensin-converting enzyme was decreased by 90% with simultaneous increases in plasma renin activity and angiotensin I concentration; aldosterone and vasopressin levels, blood pressure and heart rate were not modified. Dopamine depressed mean arterial pressure by 30% and increased heart rate (8%) in controls. Dopamine infusion did not affect either plasma renin activity or angiotensin I concentration or angiotensin-converting enzyme activity in control animals. But in perindopril pretreated animals it further increased plasma renin activity (88%) and angiotensin I concentration (35%). Finally, in controls, dopamine infusion increased plasma vasopressin concentrations (91%) whereas this increase did not occur in perindopril treated animals.", "contents": "Endocrine and hemodynamic responses to dopamine infusion in the guinea-pig: effects of ACE inhibition with perindopril. The effects of dopamine on plasma renin-angiotensin-aldosterone system vasopressin levels and blood pressure were studied in anesthetized guinea-pig. The inhibition of the angiotensin converting enzyme with perindopril permitted assessment of the role of the renin-angiotensin system. In perindopril-treated guinea-pigs, the activity of angiotensin-converting enzyme was decreased by 90% with simultaneous increases in plasma renin activity and angiotensin I concentration; aldosterone and vasopressin levels, blood pressure and heart rate were not modified. Dopamine depressed mean arterial pressure by 30% and increased heart rate (8%) in controls. Dopamine infusion did not affect either plasma renin activity or angiotensin I concentration or angiotensin-converting enzyme activity in control animals. But in perindopril pretreated animals it further increased plasma renin activity (88%) and angiotensin I concentration (35%). Finally, in controls, dopamine infusion increased plasma vasopressin concentrations (91%) whereas this increase did not occur in perindopril treated animals."} {"id": "PMID:1282388", "title": "Characteristics of ryanodine-induced tetani in the perfused rat heart. Tetanic tension is not the highest force that cardiac muscle can generate.", "content": "The aim of the present study was to elucidate the conditions required to obtain tetanic contractions in rat intact heart and to investigate whether tetanic tension was actually the maximal tension that isolated rat heart is able to generate. Experiments were performed on isolated rat hearts (Langendorff technique) perfused at constant coronary flow (8-9 ml/min). Rapid repetitive stimulation (400 to 3000 pulses/min) failed to elicit a fused tetanus. The first twitch that occurred at the end of the rapid stimulation period was a potentiated beat (PSP) of significantly greater magnitude than that of the regular twitch. This potentiation declined in successive beats. When rapid electrical stimulation (600 to 3000 pulses/min) was applied to hearts treated with 5 x 10(-6) M ryanodine, the result was a fused and steady tetanic tension. Ryanodine suppressed PSP. Tetanic tension could be graded by stepwise increase of [Ca2+]o from 0.25 to 5 mM. Maximal tetanic tension occurred at a [Ca2+]o between 3.85 and 5 mM. At any of the [Ca2+]o, tetanic tension was significantly greater than the tension of the twitch obtained at approximately the natural frequency of rat heart in the intact animal (250 beats/min) but it did not differ significantly from the twitch obtained at 100 beats/min. Moreover, the tension of PSP at 0.25 and 1.35 mM [Ca2+]o was significantly greater than the maximal tetanic tension that could be obtained. Similar results to that obtained with ryanodine, were obtained in additional experiments in which caffeine was used to evoke tetanic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Characteristics of ryanodine-induced tetani in the perfused rat heart. Tetanic tension is not the highest force that cardiac muscle can generate. The aim of the present study was to elucidate the conditions required to obtain tetanic contractions in rat intact heart and to investigate whether tetanic tension was actually the maximal tension that isolated rat heart is able to generate. Experiments were performed on isolated rat hearts (Langendorff technique) perfused at constant coronary flow (8-9 ml/min). Rapid repetitive stimulation (400 to 3000 pulses/min) failed to elicit a fused tetanus. The first twitch that occurred at the end of the rapid stimulation period was a potentiated beat (PSP) of significantly greater magnitude than that of the regular twitch. This potentiation declined in successive beats. When rapid electrical stimulation (600 to 3000 pulses/min) was applied to hearts treated with 5 x 10(-6) M ryanodine, the result was a fused and steady tetanic tension. Ryanodine suppressed PSP. Tetanic tension could be graded by stepwise increase of [Ca2+]o from 0.25 to 5 mM. Maximal tetanic tension occurred at a [Ca2+]o between 3.85 and 5 mM. At any of the [Ca2+]o, tetanic tension was significantly greater than the tension of the twitch obtained at approximately the natural frequency of rat heart in the intact animal (250 beats/min) but it did not differ significantly from the twitch obtained at 100 beats/min. Moreover, the tension of PSP at 0.25 and 1.35 mM [Ca2+]o was significantly greater than the maximal tetanic tension that could be obtained. Similar results to that obtained with ryanodine, were obtained in additional experiments in which caffeine was used to evoke tetanic contraction.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282389", "title": "Rat neonates renal function after beta-receptors and adrenoceptors blockade during pregnancy.", "content": "Pregnant Wistar rats were given by subcutaneous route 1 of 3 different adrenoreceptor blockers, 2 of them mainly beta-blockers. P5 and P7 group received propranolol (5 and 7 mg/kg respectively), L10 and L20 groups received labetalol (10 and 20 mg/kg) and B5 group received betaxolol (5 mg/kg). Drugs were given daily from the 7th to the 16th day of gestation. A control group received saline injections. 16 out 24 treated mothers delivered prematurely on the 21st day of gestation. Functional renal parameters were studied in neonates on the first day of life. Renal function of the full term rats prenatally exposed were compared with controls. Average body weight was higher in P5 but lower in L10-L20-B5 groups. Diuresis increased in L20. Creatinine clearance, urinary/plasmatic creatinine ratio and urea clearance decreased in L10-L20 groups and fractional excretion of H2O increased in L20. Thus these adreno- and beta-blockers given to pregnant rats induced a shorter gestation. Moderate functional renal effects were observed in all neonates.", "contents": "Rat neonates renal function after beta-receptors and adrenoceptors blockade during pregnancy. Pregnant Wistar rats were given by subcutaneous route 1 of 3 different adrenoreceptor blockers, 2 of them mainly beta-blockers. P5 and P7 group received propranolol (5 and 7 mg/kg respectively), L10 and L20 groups received labetalol (10 and 20 mg/kg) and B5 group received betaxolol (5 mg/kg). Drugs were given daily from the 7th to the 16th day of gestation. A control group received saline injections. 16 out 24 treated mothers delivered prematurely on the 21st day of gestation. Functional renal parameters were studied in neonates on the first day of life. Renal function of the full term rats prenatally exposed were compared with controls. Average body weight was higher in P5 but lower in L10-L20-B5 groups. Diuresis increased in L20. Creatinine clearance, urinary/plasmatic creatinine ratio and urea clearance decreased in L10-L20 groups and fractional excretion of H2O increased in L20. Thus these adreno- and beta-blockers given to pregnant rats induced a shorter gestation. Moderate functional renal effects were observed in all neonates."} {"id": "PMID:1282390", "title": "Studies on gamma-aminobutyrate aminotransferase (GABA-T) activities in human and rodent brain homogenates.", "content": "Differences in the kinetic properties of brain gamma-aminobutyrate aminotransferase (GABA-transaminase; GABA-T) in different species are described in the present investigation. In both rat and human brain enzymes, the effect of temperature on the activity was studied. The maximal activity, for a 30-min incubation period, was attained at an incubation temperature of 45 degrees C for rat and 56 degrees C for human brain tissue. The addition of plasma or plasma proteins was found to induce a two-fold increase of the activity of rat brain GABA-T, whereas a slight inhibitory effect on human brain enzyme and no effect on mouse brain enzyme was observed. The species differences are shown to be the results of differences in the binding of the cofactor pyridoxal phosphate to the apoprotein, which are revealed when the free concentration of pyridoxal phosphate is reduced by binding to serum albumin.", "contents": "Studies on gamma-aminobutyrate aminotransferase (GABA-T) activities in human and rodent brain homogenates. Differences in the kinetic properties of brain gamma-aminobutyrate aminotransferase (GABA-transaminase; GABA-T) in different species are described in the present investigation. In both rat and human brain enzymes, the effect of temperature on the activity was studied. The maximal activity, for a 30-min incubation period, was attained at an incubation temperature of 45 degrees C for rat and 56 degrees C for human brain tissue. The addition of plasma or plasma proteins was found to induce a two-fold increase of the activity of rat brain GABA-T, whereas a slight inhibitory effect on human brain enzyme and no effect on mouse brain enzyme was observed. The species differences are shown to be the results of differences in the binding of the cofactor pyridoxal phosphate to the apoprotein, which are revealed when the free concentration of pyridoxal phosphate is reduced by binding to serum albumin."} {"id": "PMID:1282391", "title": "[Blood lactate in the steeplechase horse: triangular and rectangular series of steps during short duration races].", "content": "Five steeplechase race horses were observed during incremental and constant-load exercises with the aim of separating effects of work rate and time on blood lactate. Each independent exercise (an incremental and three constant load tests) was a sequence of three two-minute runs, separated by two one-minute rest intervals for jugular blood sampling. The following observations were made: 1. During constant load exercises, in the five horses, blood lactate stabilized below 4 mmol.l-1: lactatemia critical velocity (LVC) = 3.33 +/- 0.16 mmol.l-1. Nevertheless, VCL, critical lactate velocity inducing LVC, was not statistically different from VS4, velocity inducing a 4 mmol.l-1 blood lactate during incremental tests. Remaining reticent on the meaning of \"lactate threshold\" often attributed to VS4, an incremental exercise thus seemed pertinent for routine long-term surveys of endurance. 2. If delta L is the blood lactate increase within a single short run, delta L increases linearly with running velocity for an incremental test, allowing the calculation of a \"null\" velocity, the highest velocity for which there is no significant lactate increase. For independent runs, delta L increased exponentially with velocity, with noticeable differences between horses. This individual short-term functional adaptation variability could be considered in assessment and follow-up of race horse fitness.", "contents": "[Blood lactate in the steeplechase horse: triangular and rectangular series of steps during short duration races]. Five steeplechase race horses were observed during incremental and constant-load exercises with the aim of separating effects of work rate and time on blood lactate. Each independent exercise (an incremental and three constant load tests) was a sequence of three two-minute runs, separated by two one-minute rest intervals for jugular blood sampling. The following observations were made: 1. During constant load exercises, in the five horses, blood lactate stabilized below 4 mmol.l-1: lactatemia critical velocity (LVC) = 3.33 +/- 0.16 mmol.l-1. Nevertheless, VCL, critical lactate velocity inducing LVC, was not statistically different from VS4, velocity inducing a 4 mmol.l-1 blood lactate during incremental tests. Remaining reticent on the meaning of \"lactate threshold\" often attributed to VS4, an incremental exercise thus seemed pertinent for routine long-term surveys of endurance. 2. If delta L is the blood lactate increase within a single short run, delta L increases linearly with running velocity for an incremental test, allowing the calculation of a \"null\" velocity, the highest velocity for which there is no significant lactate increase. For independent runs, delta L increased exponentially with velocity, with noticeable differences between horses. This individual short-term functional adaptation variability could be considered in assessment and follow-up of race horse fitness."} {"id": "PMID:1282395", "title": "[Study on the relationship between toddler temperament and development (second report)--the relationship between toddler temperament and developmental delay].", "content": "The purpose of this study is to clarify the relationship between toddler temperament and developmental delay, and to examine whether the result could be adapted to the health practice of mother and child. As the conceptual framework, we used A. J. Sameroff's transactional model. Questionnaires concerning toddler temperament, rearing environment and toddler development were sent to mothers whose children were scheduled to receive 1 year and 6 months child health examinations, and collected 306 responses. We assessed the developmental status of 41 children among the 306 by means of the Japanese edition of the Denver Developmental Screening Test. All 306 children were classified into either the developmental delayed group (30) or the normal group (275). The data analyses were conducted both quantitatively and qualitatively with the following results. Compared with normal children, developmentally delayed children showed these characteristics: (1) The temperamental category scores of adaptability and persistence were higher, indicating low adaptability and persistence. The prevalence of difficult child, slow to warm up (STWU) child and intermediate high child was relatively higher, with STWU child the highest. (2) The score for the rearing environment was lower. (3) There were cases where disagreement between a child's temperament and the mother's rearing behavior had an influence on the child's development. As a conclusion, these results indicate that a child's temperament must be considered developmental and child-rearing counseling in child health examinations.", "contents": "[Study on the relationship between toddler temperament and development (second report)--the relationship between toddler temperament and developmental delay]. The purpose of this study is to clarify the relationship between toddler temperament and developmental delay, and to examine whether the result could be adapted to the health practice of mother and child. As the conceptual framework, we used A. J. Sameroff's transactional model. Questionnaires concerning toddler temperament, rearing environment and toddler development were sent to mothers whose children were scheduled to receive 1 year and 6 months child health examinations, and collected 306 responses. We assessed the developmental status of 41 children among the 306 by means of the Japanese edition of the Denver Developmental Screening Test. All 306 children were classified into either the developmental delayed group (30) or the normal group (275). The data analyses were conducted both quantitatively and qualitatively with the following results. Compared with normal children, developmentally delayed children showed these characteristics: (1) The temperamental category scores of adaptability and persistence were higher, indicating low adaptability and persistence. The prevalence of difficult child, slow to warm up (STWU) child and intermediate high child was relatively higher, with STWU child the highest. (2) The score for the rearing environment was lower. (3) There were cases where disagreement between a child's temperament and the mother's rearing behavior had an influence on the child's development. As a conclusion, these results indicate that a child's temperament must be considered developmental and child-rearing counseling in child health examinations."} {"id": "PMID:1282392", "title": "Dietary calcium on vascular reactivity in normotensive and spontaneously hypertensive rats.", "content": "Vascular reactivity and systolic blood pressure (SBP) were studied in tail artery rings isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive, Wistar-Kyoto rats (WKY). After a control week on a diet with 1% of calcium, the animals were randomly assigned to three groups, which were fed with 1% (control), 0.4% (low) or 2.5% (high) dietary calcium. Both vascular reactivity and SBP were studied in the same animal during 9 weeks after changing diets. In the SHRSP rats on high Ca diet, maximal contractile responses to norepinephrine and serotonin (10(-10) to 10(-4) M) and to KCl (5 to 105 mM) were markedly decreased at the end of the study with respect to the control diet. These vascular changes were accompanied by a decrease of SBP in the same animals. Low calcium diet prevented the age-related increase of SBP in SHRSP rats and produced vascular changes of a lesser magnitude. WKY rats showed no significant modifications of SBP or vascular reactivity. Since plasmatic Ca2+ levels were not altered, the changes detected could not be attributed to a direct depressant effect of high calcium on the vascular smooth muscle cell (i.e. a \"stabilizing action\" of calcium). It is speculated that high dietary calcium could modulate the synthesis of calcium binding proteins of the plasma membrane, decreasing vascular reactivity and the elevated vascular resistance which is usually present in hypertension.", "contents": "Dietary calcium on vascular reactivity in normotensive and spontaneously hypertensive rats. Vascular reactivity and systolic blood pressure (SBP) were studied in tail artery rings isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive, Wistar-Kyoto rats (WKY). After a control week on a diet with 1% of calcium, the animals were randomly assigned to three groups, which were fed with 1% (control), 0.4% (low) or 2.5% (high) dietary calcium. Both vascular reactivity and SBP were studied in the same animal during 9 weeks after changing diets. In the SHRSP rats on high Ca diet, maximal contractile responses to norepinephrine and serotonin (10(-10) to 10(-4) M) and to KCl (5 to 105 mM) were markedly decreased at the end of the study with respect to the control diet. These vascular changes were accompanied by a decrease of SBP in the same animals. Low calcium diet prevented the age-related increase of SBP in SHRSP rats and produced vascular changes of a lesser magnitude. WKY rats showed no significant modifications of SBP or vascular reactivity. Since plasmatic Ca2+ levels were not altered, the changes detected could not be attributed to a direct depressant effect of high calcium on the vascular smooth muscle cell (i.e. a \"stabilizing action\" of calcium). It is speculated that high dietary calcium could modulate the synthesis of calcium binding proteins of the plasma membrane, decreasing vascular reactivity and the elevated vascular resistance which is usually present in hypertension."} {"id": "PMID:1282393", "title": "Seasonal changes in blood parameters in the bat species Rhinolophus ferrumequinum and miniopterus schreibersi.", "content": "Intersexual and seasonal comparisons of erythrocyte number, hematocrit, and hemoglobin concentration were conducted for two old world temperate bats, Rhinolophus ferrumequinum and Miniopterus schreibersi. Both species had many small erythrocytes and elevated hemoglobin concentrations. Seasonal differences in erythrocyte count, hemoglobin concentration, and mean cell volume were found in each species. The increase in the number of small erythrocytes in the warm season may be related to heightened activity of the bats during this period. High blood-oxygen capacities associated with high hemoglobin concentrations and hematocrit values increase oxygen delivery to tissues in species with small body size and high metabolic rates.", "contents": "Seasonal changes in blood parameters in the bat species Rhinolophus ferrumequinum and miniopterus schreibersi. Intersexual and seasonal comparisons of erythrocyte number, hematocrit, and hemoglobin concentration were conducted for two old world temperate bats, Rhinolophus ferrumequinum and Miniopterus schreibersi. Both species had many small erythrocytes and elevated hemoglobin concentrations. Seasonal differences in erythrocyte count, hemoglobin concentration, and mean cell volume were found in each species. The increase in the number of small erythrocytes in the warm season may be related to heightened activity of the bats during this period. High blood-oxygen capacities associated with high hemoglobin concentrations and hematocrit values increase oxygen delivery to tissues in species with small body size and high metabolic rates."} {"id": "PMID:1282394", "title": "[Variations in the testicular response to HCG during the perinatal period in the rat: influence of estrogens].", "content": "The variations of the testicular responsiveness to hCG and the implication of the maternal estrogens in the functioning of the testes were studied in the perinatal male rat. Male rat fetuses treated with hCG at the end of gestation failed to show an increase in serum testosterone (T). The lack of testicular responsiveness to hCG in the fetus is neither due to anesthesia nor to a blocking effect of estrogens directly on the testes. On the other hand, hCG injected either at 4 h or at 48 h after birth increases serum T. The administration of 5 micrograms of estradiol 17 beta (E2) to the newborn male rat at the time of birth blocks the expression of the postpartum testosterone surge. The fall in the plasma estrogens and the increase of the testicular sensitivity to gonadotropic stimulation at the time of birth are factors which are very likely implicated in the determinism of the neonatal testicular hyperactivity.", "contents": "[Variations in the testicular response to HCG during the perinatal period in the rat: influence of estrogens]. The variations of the testicular responsiveness to hCG and the implication of the maternal estrogens in the functioning of the testes were studied in the perinatal male rat. Male rat fetuses treated with hCG at the end of gestation failed to show an increase in serum testosterone (T). The lack of testicular responsiveness to hCG in the fetus is neither due to anesthesia nor to a blocking effect of estrogens directly on the testes. On the other hand, hCG injected either at 4 h or at 48 h after birth increases serum T. The administration of 5 micrograms of estradiol 17 beta (E2) to the newborn male rat at the time of birth blocks the expression of the postpartum testosterone surge. The fall in the plasma estrogens and the increase of the testicular sensitivity to gonadotropic stimulation at the time of birth are factors which are very likely implicated in the determinism of the neonatal testicular hyperactivity."} {"id": "PMID:1282397", "title": "Dural arteriovenous malformation and sinus thromboses in a patient with prostate cancer: an autopsy case.", "content": "A 67-year old man with prostate cancer showed Balint's syndrome, memory disturbance, anosognosia and hallucinations after having been comatose. Radiological findings indicated bilateral dural arteriovenous malformation (DAVM) and thrombosis at the bilateral transverse sinuses and superior sagittal sinus. Pathological findings showed abnormally dilated veins, diffuse neuron loss and gliosis in the parieto-occipital lobe. The chlormadinone and prostate cancer are speculated to have caused the dural sinus thrombosis which probably induced the DAVM.", "contents": "Dural arteriovenous malformation and sinus thromboses in a patient with prostate cancer: an autopsy case. A 67-year old man with prostate cancer showed Balint's syndrome, memory disturbance, anosognosia and hallucinations after having been comatose. Radiological findings indicated bilateral dural arteriovenous malformation (DAVM) and thrombosis at the bilateral transverse sinuses and superior sagittal sinus. Pathological findings showed abnormally dilated veins, diffuse neuron loss and gliosis in the parieto-occipital lobe. The chlormadinone and prostate cancer are speculated to have caused the dural sinus thrombosis which probably induced the DAVM."} {"id": "PMID:1282399", "title": "[Uses of duck hepatitis B virus polymerase and reverse transcriptase in the evaluation of anti-hepatitis B virus drugs].", "content": "The method of DHBV replication complexes (RCs) purification was modified. In order to screen anti-HBV drugs from Chinese medicinal herbs, the inhibitory effects of the extracts of 14 Chinese recipes and herbs, 30 compounds isolated from Chinese herbs on DHBV DNA polymerase (DNAP) and reverse transcriptase (RT) have been studied. The results showed that extracts of Xiao Chai Hu Tang (small Bupleurum decoction) inhibited DHBV DNAP and RT in less extent. Of the 7 herbs, the components of Xiao Chai Hu Tang, the extracts of S. baicalensis and P. ternata potently inhibited DHBV RT, their concentration of reducing enzyme activity by 50% (IC50) was 1.25 and 1.6 mg/ml respectively. Furthermore, it has been proved that S. baicalensis inhibited DHBV DNA replication in ducklings. It also was found the extract of P. cuspidatum inhibited DHBV RT with IC50 of 1.76 mg/ml. Nine of thirty isolated compounds inhibited both DHBV DNAP and RT in less extent under high concentration, while other did not.", "contents": "[Uses of duck hepatitis B virus polymerase and reverse transcriptase in the evaluation of anti-hepatitis B virus drugs]. The method of DHBV replication complexes (RCs) purification was modified. In order to screen anti-HBV drugs from Chinese medicinal herbs, the inhibitory effects of the extracts of 14 Chinese recipes and herbs, 30 compounds isolated from Chinese herbs on DHBV DNA polymerase (DNAP) and reverse transcriptase (RT) have been studied. The results showed that extracts of Xiao Chai Hu Tang (small Bupleurum decoction) inhibited DHBV DNAP and RT in less extent. Of the 7 herbs, the components of Xiao Chai Hu Tang, the extracts of S. baicalensis and P. ternata potently inhibited DHBV RT, their concentration of reducing enzyme activity by 50% (IC50) was 1.25 and 1.6 mg/ml respectively. Furthermore, it has been proved that S. baicalensis inhibited DHBV DNA replication in ducklings. It also was found the extract of P. cuspidatum inhibited DHBV RT with IC50 of 1.76 mg/ml. Nine of thirty isolated compounds inhibited both DHBV DNAP and RT in less extent under high concentration, while other did not."} {"id": "PMID:1282396", "title": "High resistance to cucumber mosaic virus conferred by satellite RNA and coat protein in transgenic commercial tobacco cultivar G-140.", "content": "A chimeric vector was constructed to express cucumber mosaic virus (CMV) satellite (Sat) RNA and coat protein (CP). Transgenic lines of tobacco cultivar G-140 expressing CP and Sat-RNA were obtained; these lines had high resistance to CMV. Fifty to 70% of the transgenic plants were symptomless 90 days after inoculation with 25-50 micrograms/ml of CMV. Resistance was about twice that conferred by the Sat-RNA or the CP gene alone in transformed plants.", "contents": "High resistance to cucumber mosaic virus conferred by satellite RNA and coat protein in transgenic commercial tobacco cultivar G-140. A chimeric vector was constructed to express cucumber mosaic virus (CMV) satellite (Sat) RNA and coat protein (CP). Transgenic lines of tobacco cultivar G-140 expressing CP and Sat-RNA were obtained; these lines had high resistance to CMV. Fifty to 70% of the transgenic plants were symptomless 90 days after inoculation with 25-50 micrograms/ml of CMV. Resistance was about twice that conferred by the Sat-RNA or the CP gene alone in transformed plants."} {"id": "PMID:1282400", "title": "Dynamic aspects of AMPs in the kidney in physiological conditions--their metabolism and turnover.", "content": "The past few decades have witnessed a number of studies on AMPs in the kidney. Almost all of these studies, however, have dealt with the quantitative and qualitative analysis of AMPs in the kidney using biochemical techniques, whereas the dynamic aspect of AMPs in the kidney has been overlooked and its metabolism and turnover have never been emphasized. On the other hand, the kidneys removed from humans and experimental animals revealed a wide variety in interstitial tissue in the medulla microscopically and in the papilla of the kidney macroscopically. The reasons for these variations in the medulla, its mechanism and the matrical component have not yet been clarified. In an effort to clarify these points, we herein describe our study on the dynamic aspect of AMPs in kidney histologically in relation to their biological turnover which we employed several staining methods. Our results revealed that there was a very active turnover of AMPs present in the kidney confirming that the kidney plays an important role physiologically in AMP metabolism. The degree of the turnover of AMPs in the kidney varies from case to case. In the active phase, AMPs are excreted in the glomerulus and reabsorbed in the proximal portion of the collecting tubules. Most of the absorbed AMPs are finally drained through the lymphatic vessels in situ and a few are excreted into the urine. Contrary cases have been demonstrated, however, only were a few AMPs were noted throughout the nephrons in the kidney. AMP turnover in the kidney is unexpectedly remarkable. The medulla, which has been considered less important, in fact, plays a key role in AMP metabolism.", "contents": "Dynamic aspects of AMPs in the kidney in physiological conditions--their metabolism and turnover. The past few decades have witnessed a number of studies on AMPs in the kidney. Almost all of these studies, however, have dealt with the quantitative and qualitative analysis of AMPs in the kidney using biochemical techniques, whereas the dynamic aspect of AMPs in the kidney has been overlooked and its metabolism and turnover have never been emphasized. On the other hand, the kidneys removed from humans and experimental animals revealed a wide variety in interstitial tissue in the medulla microscopically and in the papilla of the kidney macroscopically. The reasons for these variations in the medulla, its mechanism and the matrical component have not yet been clarified. In an effort to clarify these points, we herein describe our study on the dynamic aspect of AMPs in kidney histologically in relation to their biological turnover which we employed several staining methods. Our results revealed that there was a very active turnover of AMPs present in the kidney confirming that the kidney plays an important role physiologically in AMP metabolism. The degree of the turnover of AMPs in the kidney varies from case to case. In the active phase, AMPs are excreted in the glomerulus and reabsorbed in the proximal portion of the collecting tubules. Most of the absorbed AMPs are finally drained through the lymphatic vessels in situ and a few are excreted into the urine. Contrary cases have been demonstrated, however, only were a few AMPs were noted throughout the nephrons in the kidney. AMP turnover in the kidney is unexpectedly remarkable. The medulla, which has been considered less important, in fact, plays a key role in AMP metabolism."} {"id": "PMID:1282398", "title": "Functional changes of alveolar macrophages in carragheenan-induced aspiration pneumonia model mice.", "content": "Alveolar macrophages (AMs) are cells with unique characteristics because of their localization in the aerobic environment and are receiving stimuli by inhalation. To estimate the functional changes of AMs induced by inflammation, a murine model of aspiration pneumonia was made by an intratracheal injection with carragheenan, whose mortality rate was approximately 25%. The cell component which increased predominantly in the inflammatory site was polymorphonuclear leukocytes, and the number of AMs did not show a remarkable increment. Control group showed a high level of intracellular oxidation of 2'7'-dichlorofluorescin (DCFH) by AMs, while that in carragheenan-treated mice decreased significantly (p < 0.05). There were two populations in AMs classified according to the oxidative activity of DCFH; the population showing high oxidative activity of DCFH was asialo GM1 positive, in contrast, that with lower oxidative activity was asialo GM1 negative. Decrease in DCFH-oxidative activity of AMs in control group was observed after a treatment with KCN or deferoxamine. But in the carragheenan-treated group, this decrease was not observed after treatment with KCN. These results show that both oxygen-derived radical produced in mitochondria, which is inhibited by KCN, and cytoplasmic OH radical, which is selectively inhibited by deferoxamine, are concerned with intracellular oxidation of DCFH by AMs, and that a decrease in DCFH-oxidative activity in the carragheenan-treated group was attributed to the depression of mitochondrial respiration. Nevertheless, increased expressions of Ia and F4/80 in AMs of the carragheenan-treated group were observed and phagocytic activity was well preserved at the control level. These results suggest that AMs may play a crucial role, as well as differentiated phagocytes possessing antigen-presenting ability and/or digestive activity against various types of foreign bodies despite showing an obvious decrement in oxidative activity. These results imply that AMs have a strong oxidative activity and deal with various types of antigens in normal states, but in case of acute inflammation they will change into mature type macrophages with high expression of class II molecules which correlates with an antigen-presenting capacity.", "contents": "Functional changes of alveolar macrophages in carragheenan-induced aspiration pneumonia model mice. Alveolar macrophages (AMs) are cells with unique characteristics because of their localization in the aerobic environment and are receiving stimuli by inhalation. To estimate the functional changes of AMs induced by inflammation, a murine model of aspiration pneumonia was made by an intratracheal injection with carragheenan, whose mortality rate was approximately 25%. The cell component which increased predominantly in the inflammatory site was polymorphonuclear leukocytes, and the number of AMs did not show a remarkable increment. Control group showed a high level of intracellular oxidation of 2'7'-dichlorofluorescin (DCFH) by AMs, while that in carragheenan-treated mice decreased significantly (p < 0.05). There were two populations in AMs classified according to the oxidative activity of DCFH; the population showing high oxidative activity of DCFH was asialo GM1 positive, in contrast, that with lower oxidative activity was asialo GM1 negative. Decrease in DCFH-oxidative activity of AMs in control group was observed after a treatment with KCN or deferoxamine. But in the carragheenan-treated group, this decrease was not observed after treatment with KCN. These results show that both oxygen-derived radical produced in mitochondria, which is inhibited by KCN, and cytoplasmic OH radical, which is selectively inhibited by deferoxamine, are concerned with intracellular oxidation of DCFH by AMs, and that a decrease in DCFH-oxidative activity in the carragheenan-treated group was attributed to the depression of mitochondrial respiration. Nevertheless, increased expressions of Ia and F4/80 in AMs of the carragheenan-treated group were observed and phagocytic activity was well preserved at the control level. These results suggest that AMs may play a crucial role, as well as differentiated phagocytes possessing antigen-presenting ability and/or digestive activity against various types of foreign bodies despite showing an obvious decrement in oxidative activity. These results imply that AMs have a strong oxidative activity and deal with various types of antigens in normal states, but in case of acute inflammation they will change into mature type macrophages with high expression of class II molecules which correlates with an antigen-presenting capacity."} {"id": "PMID:1282401", "title": "Leptospiral antigens in the liver of experimentally infected guinea pig and their relation to the morphogenesis of liver damage.", "content": "In order to investigate the morphogenes of experimental leptospirosis by morphologic and immunohistologic methods, 24 guinea-pigs were inoculated intraperitoneally with L. interrogans serogroup Icterohaemorrhagiae. They were divided in 6 groups, sacrificed from the 1st to the 6th day of infection. Semiquantitative analyses of histopathological liver lesions were performed in 1 micron sections of tissue embedded in glycol-methacrylate. The distribution of leptospiral antigen (L. Ag) and its glycolipoprotein (GLP) was demonstrated by peroxidase-antiperoxidase on paraffin embedded tissue. Significant lesions appeared at the 4th day of infection, progressing to a peak on the 6th day. Inflammation was associated with injury of the portal triad. Liver cells showed either swelling or acidophilic degeneration and necrosis, together with loss of cell cohesion, leading to disarray of liver cell plates. Mitochondria were found progressively enlarged and irregularly distributed. L. Ag expression was parallel to the morphological changes. Portal distribution was significant at the 4th day and on later stages centrilobular localization became predominant. Spiral forms suggestive of intact leptospires were initially found but, chiefly at the 6th day, L. Ag was seen in granules, probably resulting from phagocytosis. GLP staining was similar to granular L. Ag in morphology, and distribution. Cytokeratin condensation was seen in liver cells with acidophilic necrosis and was marked in areas of disorganization of cell plates. Our findings lead us to hypothesize a direct leptospiral cytotoxic effect on endothelial and on liver-cell membranes. At first, leptospires themselves would induce subcellular changes acting mainly on membrane permeability. Afterwards, their granular forms, including GLP, would act as adjuvant factors. These findings demonstrate that the disarray of liver cell plates at the late phase of the disease is genuine.", "contents": "Leptospiral antigens in the liver of experimentally infected guinea pig and their relation to the morphogenesis of liver damage. In order to investigate the morphogenes of experimental leptospirosis by morphologic and immunohistologic methods, 24 guinea-pigs were inoculated intraperitoneally with L. interrogans serogroup Icterohaemorrhagiae. They were divided in 6 groups, sacrificed from the 1st to the 6th day of infection. Semiquantitative analyses of histopathological liver lesions were performed in 1 micron sections of tissue embedded in glycol-methacrylate. The distribution of leptospiral antigen (L. Ag) and its glycolipoprotein (GLP) was demonstrated by peroxidase-antiperoxidase on paraffin embedded tissue. Significant lesions appeared at the 4th day of infection, progressing to a peak on the 6th day. Inflammation was associated with injury of the portal triad. Liver cells showed either swelling or acidophilic degeneration and necrosis, together with loss of cell cohesion, leading to disarray of liver cell plates. Mitochondria were found progressively enlarged and irregularly distributed. L. Ag expression was parallel to the morphological changes. Portal distribution was significant at the 4th day and on later stages centrilobular localization became predominant. Spiral forms suggestive of intact leptospires were initially found but, chiefly at the 6th day, L. Ag was seen in granules, probably resulting from phagocytosis. GLP staining was similar to granular L. Ag in morphology, and distribution. Cytokeratin condensation was seen in liver cells with acidophilic necrosis and was marked in areas of disorganization of cell plates. Our findings lead us to hypothesize a direct leptospiral cytotoxic effect on endothelial and on liver-cell membranes. At first, leptospires themselves would induce subcellular changes acting mainly on membrane permeability. Afterwards, their granular forms, including GLP, would act as adjuvant factors. These findings demonstrate that the disarray of liver cell plates at the late phase of the disease is genuine."} {"id": "PMID:1282402", "title": "Regional distribution of neurofilament and calcium-binding proteins in the cingulate cortex of the macaque monkey.", "content": "The cingulate cortex is composed of morphologically and functionally distinct areas. It is considered to be a major component of the limbic system and has been shown to subserve a wide range of autonomic and somatic motor functions. The anterior and posterior regions of the cingulate cortex can be differentiated according to their thalamic afferents as well as their patterns of corticocortical connectivity. The primate cingulate cortex is traditionally divided into a series of cytoarchitectonic zones that can be distinguished along a ventral-dorsal axis of differentiation in both the anterior (areas 25, 24a, 24b, and 24c), and posterior (areas 29, 30, 23a, 23b, and 23c) regions. However, little is known about the precise cellular organization of these subareas. In the present study, we attempt to define the neuronal morphological and biochemical composition of the different cingulate cortex subareas, using antibodies to the neurofilament triplet protein and calcium-binding proteins. Results indicate that there is a strong correlation between the structure and functions of the cingulate cortex and the immunostaining patterns. For instance, distribution of neurofilament-rich pyramidal neurons parallels that of specific corticocortical and corticosubcortical systems and is a useful marker to delineate the cingulate motor area. Calcium-binding protein-containing neurons display a high degree of regional and laminar specialization. In particular, parvalbumin-positive interneurons are codistributed with neurofilament-immunoreactive pyramidal cells along the ventrodorsal and rostrocaudal axes of the cingulate cortex. Calbindin- and calretinin-positive immunostaining show more monotonous laminar and regional patterns, although they exhibit a particular labeling in area 29 that may correspond to the termination of select thalamocortical afferents. These chemoarchitectural patterns of regional and laminar neuronal specialization may be envisioned as the reflection of the richness of cortical diversity in the cingulate gyrus, and make it an ideal place to explore the interplay of the distributions of various neuron types in cortical areas of known function.", "contents": "Regional distribution of neurofilament and calcium-binding proteins in the cingulate cortex of the macaque monkey. The cingulate cortex is composed of morphologically and functionally distinct areas. It is considered to be a major component of the limbic system and has been shown to subserve a wide range of autonomic and somatic motor functions. The anterior and posterior regions of the cingulate cortex can be differentiated according to their thalamic afferents as well as their patterns of corticocortical connectivity. The primate cingulate cortex is traditionally divided into a series of cytoarchitectonic zones that can be distinguished along a ventral-dorsal axis of differentiation in both the anterior (areas 25, 24a, 24b, and 24c), and posterior (areas 29, 30, 23a, 23b, and 23c) regions. However, little is known about the precise cellular organization of these subareas. In the present study, we attempt to define the neuronal morphological and biochemical composition of the different cingulate cortex subareas, using antibodies to the neurofilament triplet protein and calcium-binding proteins. Results indicate that there is a strong correlation between the structure and functions of the cingulate cortex and the immunostaining patterns. For instance, distribution of neurofilament-rich pyramidal neurons parallels that of specific corticocortical and corticosubcortical systems and is a useful marker to delineate the cingulate motor area. Calcium-binding protein-containing neurons display a high degree of regional and laminar specialization. In particular, parvalbumin-positive interneurons are codistributed with neurofilament-immunoreactive pyramidal cells along the ventrodorsal and rostrocaudal axes of the cingulate cortex. Calbindin- and calretinin-positive immunostaining show more monotonous laminar and regional patterns, although they exhibit a particular labeling in area 29 that may correspond to the termination of select thalamocortical afferents. These chemoarchitectural patterns of regional and laminar neuronal specialization may be envisioned as the reflection of the richness of cortical diversity in the cingulate gyrus, and make it an ideal place to explore the interplay of the distributions of various neuron types in cortical areas of known function."} {"id": "PMID:1282405", "title": "Genetic novelties in mitochondrial genomes of multicellular animals.", "content": "Mitochondrial genomes of multicellular animals are mostly small, circular molecules in which 13 protein genes, two ribosomal-RNA genes and 22 transfer-RNA genes are closely packed. Substantial rearrangements of genes have only occurred between phylogenetically distant organisms. However, a wealth of genetic novelties are found among these genomes that include modified genetic codes, unorthodox translation initiation codons, and structurally modified RNA components of the mitochondrion's translation system.", "contents": "Genetic novelties in mitochondrial genomes of multicellular animals. Mitochondrial genomes of multicellular animals are mostly small, circular molecules in which 13 protein genes, two ribosomal-RNA genes and 22 transfer-RNA genes are closely packed. Substantial rearrangements of genes have only occurred between phylogenetically distant organisms. However, a wealth of genetic novelties are found among these genomes that include modified genetic codes, unorthodox translation initiation codons, and structurally modified RNA components of the mitochondrion's translation system."} {"id": "PMID:1282403", "title": "Glutamatergic excitatory responses of anterior cingulate neurons to stimulation of the mediodorsal thalamus and their regulation by GABA: an in vivo iontophoretic study.", "content": "Anatomical and physiological studies in the rat have shown projections from the medial dorsal thalamus to the anterior cingulate cortex. We used multibarrel iontophoresis to identify the neurotransmitter used in this thalamic projection. Extracellular responses were recorded from 165 cingulate neurons in anesthetized rats after electrical stimulation of the medial dorsal thalamus and vicinity. Forty-four of these cells (27%) showed an excitatory response to thalamic stimulation. In a further 40 cells that showed no baseline excitation, iontophoresis of the GABAA antagonist bicuculline methiodide revealed excitatory responses. The GABAB antagonist CGP-35348 attenuated longer-latency inhibition in 5 of 10 cells. In 23 of 49 (47%) of the above cells, AMPA antagonist iontophoresis (either CNQX or DNQX) selectively decreased the excitatory response to thalamic stimulation. The NMDA antagonist 3[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid had no such effect. These data suggest that the thalamic projection to anterior cingulate cortex is glutamatergic, acting principally via AMPA receptors, and that the response of cingulate neurons to thalamic stimulation is regulated by GABA acting at both GABAA and GABAB receptors.", "contents": "Glutamatergic excitatory responses of anterior cingulate neurons to stimulation of the mediodorsal thalamus and their regulation by GABA: an in vivo iontophoretic study. Anatomical and physiological studies in the rat have shown projections from the medial dorsal thalamus to the anterior cingulate cortex. We used multibarrel iontophoresis to identify the neurotransmitter used in this thalamic projection. Extracellular responses were recorded from 165 cingulate neurons in anesthetized rats after electrical stimulation of the medial dorsal thalamus and vicinity. Forty-four of these cells (27%) showed an excitatory response to thalamic stimulation. In a further 40 cells that showed no baseline excitation, iontophoresis of the GABAA antagonist bicuculline methiodide revealed excitatory responses. The GABAB antagonist CGP-35348 attenuated longer-latency inhibition in 5 of 10 cells. In 23 of 49 (47%) of the above cells, AMPA antagonist iontophoresis (either CNQX or DNQX) selectively decreased the excitatory response to thalamic stimulation. The NMDA antagonist 3[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid had no such effect. These data suggest that the thalamic projection to anterior cingulate cortex is glutamatergic, acting principally via AMPA receptors, and that the response of cingulate neurons to thalamic stimulation is regulated by GABA acting at both GABAA and GABAB receptors."} {"id": "PMID:1282406", "title": "Neuromodulation of vertebrate motor neuron membrane properties.", "content": "The short-term function of motor neurons is to integrate synaptic inputs converging onto the somato-dendritic membrane and to transform the net synaptic drive into spike trains. A set of voltage-gated ion channels determines the electro-responsiveness and thereby the motor neuron's input-output function. In addition, several of the decisive ion channels are transmitter controlled, which results in a flexible control of the input-output relationship.", "contents": "Neuromodulation of vertebrate motor neuron membrane properties. The short-term function of motor neurons is to integrate synaptic inputs converging onto the somato-dendritic membrane and to transform the net synaptic drive into spike trains. A set of voltage-gated ion channels determines the electro-responsiveness and thereby the motor neuron's input-output function. In addition, several of the decisive ion channels are transmitter controlled, which results in a flexible control of the input-output relationship."} {"id": "PMID:1282404", "title": "Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain.", "content": "Recent postmortem investigations have suggested that schizophrenia may involve a defect in associative information processing in the upper layers of limbic cortex. One of these studies reported that vertical processes visualized with antibodies against the neurofilament 200K subunit (NFP-200K) of the axon cytoskeleton were increased in density in layer II and upper portions of layer IIIa of the cingulate region of schizophrenic individuals. Based on this latter finding, it was hypothesized that there may be a superbundance of associative afferents to this region. To explore this possibility further, an immunoperoxidase localization of the amino acid glutamate has been employed to visualize vertical fibers in layers II and IIIa of postmortem anterior cingulate cortex in both normal controls (n = 15) and schizophrenics (n = 17). Vertical fibers were distinguished according to small or large calibers and were differentially counted with a blind computer-assisted technique. The schizophrenic group showed a markedly higher density (77.8%) of small-caliber glutamate-immunoreactive vertical fibers when compared to controls; the density of large-caliber vertical fibers also showed a similar, though smaller (30.2%), increase in the schizophrenic group. There were no differences in the density of either small- or large-caliber processes in prefrontal cortex of the two groups. The effects of age, postmortem interval, fixation, and neuroleptic exposure do not account for the differences between the normal and schizophrenic subjects. Taking together their small caliber, vertical orientation, localization in superficial layers, and marked glutamate immunoreactivity, it seems plausible that the fibers showing an increased density in schizophrenics may be glutamatergic afferents, possibly ones that are associative in nature.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Increased density of glutamate-immunoreactive vertical processes in superficial laminae in cingulate cortex of schizophrenic brain. Recent postmortem investigations have suggested that schizophrenia may involve a defect in associative information processing in the upper layers of limbic cortex. One of these studies reported that vertical processes visualized with antibodies against the neurofilament 200K subunit (NFP-200K) of the axon cytoskeleton were increased in density in layer II and upper portions of layer IIIa of the cingulate region of schizophrenic individuals. Based on this latter finding, it was hypothesized that there may be a superbundance of associative afferents to this region. To explore this possibility further, an immunoperoxidase localization of the amino acid glutamate has been employed to visualize vertical fibers in layers II and IIIa of postmortem anterior cingulate cortex in both normal controls (n = 15) and schizophrenics (n = 17). Vertical fibers were distinguished according to small or large calibers and were differentially counted with a blind computer-assisted technique. The schizophrenic group showed a markedly higher density (77.8%) of small-caliber glutamate-immunoreactive vertical fibers when compared to controls; the density of large-caliber vertical fibers also showed a similar, though smaller (30.2%), increase in the schizophrenic group. There were no differences in the density of either small- or large-caliber processes in prefrontal cortex of the two groups. The effects of age, postmortem interval, fixation, and neuroleptic exposure do not account for the differences between the normal and schizophrenic subjects. Taking together their small caliber, vertical orientation, localization in superficial layers, and marked glutamate immunoreactivity, it seems plausible that the fibers showing an increased density in schizophrenics may be glutamatergic afferents, possibly ones that are associative in nature.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282407", "title": "Temporomandibular joint innervation in rats: a horseradish peroxidase study.", "content": "In the present study, we have used the horseradish peroxidase (HRP) retrograde transport technique to map the trigeminal primary afferent and motor neurons that innervate the temporomandibular joint (TMJ) and the lateral pterygoid muscle (LPM). One to 3.0 microL of 4% wheatgerm agglutinin conjugated horseradish peroxidase (HRP-WGA) solution was introduced unilaterally into the joint cavity of twelve Sprague-Dawley rats. Injections were made from the above, following trephining of the zygomatic arch with a dental bur. Seventy-two hours after surgery, the animals were sacrificed via perfusion-fixation through the left ventricle. The TMJ, both trigeminal ganglia and brain stem were removed, sectioned serially at 50 microns, and reacted according to the tetramethyl benzidine (TMB) technique of Mesulam. Tissues were then examined at the light microscopic level. The injection site showed that the HRP-WGA filled the upper chamber of the TMJ cavity and extended anteriorly to include the LPM. HRP injected into the joint cavity was transported retrogradely to the ipsilateral trigeminal ganglion, where numerous HRP labeled neurons were found. The greatest number of cells were localized in the dorsolateral posterior portion of the ganglion. In the brain stem, numerous labeled cells representing the motor innervation of the LPM were found in a crescent-shaped array on the ventral side of the trigeminal motor nucleus. No labeled cells were found in the mesencephalic nucleus. The results show substantial trigeminal sensory innervation of the TMJ and LPM with no central projection to the mesencephalic nucleus.", "contents": "Temporomandibular joint innervation in rats: a horseradish peroxidase study. In the present study, we have used the horseradish peroxidase (HRP) retrograde transport technique to map the trigeminal primary afferent and motor neurons that innervate the temporomandibular joint (TMJ) and the lateral pterygoid muscle (LPM). One to 3.0 microL of 4% wheatgerm agglutinin conjugated horseradish peroxidase (HRP-WGA) solution was introduced unilaterally into the joint cavity of twelve Sprague-Dawley rats. Injections were made from the above, following trephining of the zygomatic arch with a dental bur. Seventy-two hours after surgery, the animals were sacrificed via perfusion-fixation through the left ventricle. The TMJ, both trigeminal ganglia and brain stem were removed, sectioned serially at 50 microns, and reacted according to the tetramethyl benzidine (TMB) technique of Mesulam. Tissues were then examined at the light microscopic level. The injection site showed that the HRP-WGA filled the upper chamber of the TMJ cavity and extended anteriorly to include the LPM. HRP injected into the joint cavity was transported retrogradely to the ipsilateral trigeminal ganglion, where numerous HRP labeled neurons were found. The greatest number of cells were localized in the dorsolateral posterior portion of the ganglion. In the brain stem, numerous labeled cells representing the motor innervation of the LPM were found in a crescent-shaped array on the ventral side of the trigeminal motor nucleus. No labeled cells were found in the mesencephalic nucleus. The results show substantial trigeminal sensory innervation of the TMJ and LPM with no central projection to the mesencephalic nucleus."} {"id": "PMID:1282408", "title": "Successful treatment of two viable tubal pregnancies by two-step local injection.", "content": "Two viable tubal pregnancies were diagnosed by transvaginal ultrasound with a serum beta-hCG level of up to 3,004 mIU/mL in Case 1 and 16,676 mIU/mL in Case 2. Under transvaginal sonographic guidance, a local injection of potassium chloride (0.5 mL = 1.0 mEq) into the embryo was performed for the purpose of embryocide. In Case 1, a follow-up of serum beta-hCG levels showed an initial plateau and subsequent regression to negative, 49 days after the local injection. However, a persistent increase in serum beta-hCG levels was noted in Case 2 for two samples at intervals of two days during follow-up, 27,800 and 36,500 mIU/mL, in spite of the fact that no fetal cardiac activity was visible. Six days later, laparoscopy was done and methotrexate, 50 mg in 6 mL of normal saline, was injected into the ampullar mass of the right fallopian tube in two divided dosages. The serum beta-hCG levels then gradually decreased and returned to negative 60 days after the methotrexate injection. For a viable ectopic pregnancy, this new modality of two-step local injection, first with potassium chloride and then with supplemental methotrexate, separately by two procedures, may offer an additional choice of conservative treatment.", "contents": "Successful treatment of two viable tubal pregnancies by two-step local injection. Two viable tubal pregnancies were diagnosed by transvaginal ultrasound with a serum beta-hCG level of up to 3,004 mIU/mL in Case 1 and 16,676 mIU/mL in Case 2. Under transvaginal sonographic guidance, a local injection of potassium chloride (0.5 mL = 1.0 mEq) into the embryo was performed for the purpose of embryocide. In Case 1, a follow-up of serum beta-hCG levels showed an initial plateau and subsequent regression to negative, 49 days after the local injection. However, a persistent increase in serum beta-hCG levels was noted in Case 2 for two samples at intervals of two days during follow-up, 27,800 and 36,500 mIU/mL, in spite of the fact that no fetal cardiac activity was visible. Six days later, laparoscopy was done and methotrexate, 50 mg in 6 mL of normal saline, was injected into the ampullar mass of the right fallopian tube in two divided dosages. The serum beta-hCG levels then gradually decreased and returned to negative 60 days after the methotrexate injection. For a viable ectopic pregnancy, this new modality of two-step local injection, first with potassium chloride and then with supplemental methotrexate, separately by two procedures, may offer an additional choice of conservative treatment."} {"id": "PMID:1282409", "title": "[Molecular genetics of the human brain].", "content": "The review discusses the contribution of molecular genetic studies to the understanding of human brain performance and defines three genetic objectives: 1) to reveal structural or functional features of brain genes specific merely to man; 2) to outline the complete spectrum of genes involved in brain activity and their regulation; 3) to search for genes and genetic defects resulting in common mental disorders. The plasticity and great variety of brain functions are shown to be based on the unique diversity of genes actively transcribing in the brain and the molecular mechanisms of various genetic products of the same gene: alternative splicing, \"antiparallel\" coding, regulation of gene activity by signal DNA sequences. Gene search policies are described for common mental disorders such as schizophrenia, manic-depressive psychosis, Alzheimer's disease. The attempts to map defective genes by \"reverse\" genetics have proved that there is a genetic heterogeneity of these diseases. The novel directions in the study of the brain molecular genetic apparatus can be examinations of chromosomal behavior in the cells in various brain regions and genome imprinting.", "contents": "[Molecular genetics of the human brain]. The review discusses the contribution of molecular genetic studies to the understanding of human brain performance and defines three genetic objectives: 1) to reveal structural or functional features of brain genes specific merely to man; 2) to outline the complete spectrum of genes involved in brain activity and their regulation; 3) to search for genes and genetic defects resulting in common mental disorders. The plasticity and great variety of brain functions are shown to be based on the unique diversity of genes actively transcribing in the brain and the molecular mechanisms of various genetic products of the same gene: alternative splicing, \"antiparallel\" coding, regulation of gene activity by signal DNA sequences. Gene search policies are described for common mental disorders such as schizophrenia, manic-depressive psychosis, Alzheimer's disease. The attempts to map defective genes by \"reverse\" genetics have proved that there is a genetic heterogeneity of these diseases. The novel directions in the study of the brain molecular genetic apparatus can be examinations of chromosomal behavior in the cells in various brain regions and genome imprinting."} {"id": "PMID:1282410", "title": "[Nerve growth factor and the state of serotoninergic system in endogenous depression and mental retardation].", "content": "Platelet parameters of the serotonin system were studied in patients with endogenous depressions and children with late documented phenylketonuria (PKU) before and after antidepressive therapy. There was a significant decrease in the rate of back platelet uptake of 3H-serotonin and an increase in the sensitivity of serotonin receptors to serotonin in the patients before therapy and normalization of these parameters after therapy. The normalization correlated with clinical improvement in patients with endogenous depression. The course therapy with L-DOPA and the antidepressant azaphen resulted in a substantial mental improvement in children with PKU. There was a significant reduction in the ability of platelets from the patients in question to react by releasing 3H-serotonin in response to nerve growth factor stimulation of cells in vitro.", "contents": "[Nerve growth factor and the state of serotoninergic system in endogenous depression and mental retardation]. Platelet parameters of the serotonin system were studied in patients with endogenous depressions and children with late documented phenylketonuria (PKU) before and after antidepressive therapy. There was a significant decrease in the rate of back platelet uptake of 3H-serotonin and an increase in the sensitivity of serotonin receptors to serotonin in the patients before therapy and normalization of these parameters after therapy. The normalization correlated with clinical improvement in patients with endogenous depression. The course therapy with L-DOPA and the antidepressant azaphen resulted in a substantial mental improvement in children with PKU. There was a significant reduction in the ability of platelets from the patients in question to react by releasing 3H-serotonin in response to nerve growth factor stimulation of cells in vitro."} {"id": "PMID:1282412", "title": "[Longitudinal approaches to the problem of clinical heterogeneity of Alzheimer-type dementia].", "content": "A total of 160 patients with Alzheimer-type dementias (ATD), including 84 with Alzheimer's diseases (AD) and 76 with senile dementia (SD), were examined. The initial signs of the disease were analyzed by making a retrospective assessment of informative history data. The prospective follow-up involved clinical, neuropsychological and electrophysiological (EEC mapping, evoked potentials) studies by applying the standardized assessment of results. There was shown to be a set of clinical and paraclinical parameters for the status of ATD patients, indicating a distinct-quantitative and qualitative difference between patients with AD and those with SD and supporting the heterogeneity of ATD.", "contents": "[Longitudinal approaches to the problem of clinical heterogeneity of Alzheimer-type dementia]. A total of 160 patients with Alzheimer-type dementias (ATD), including 84 with Alzheimer's diseases (AD) and 76 with senile dementia (SD), were examined. The initial signs of the disease were analyzed by making a retrospective assessment of informative history data. The prospective follow-up involved clinical, neuropsychological and electrophysiological (EEC mapping, evoked potentials) studies by applying the standardized assessment of results. There was shown to be a set of clinical and paraclinical parameters for the status of ATD patients, indicating a distinct-quantitative and qualitative difference between patients with AD and those with SD and supporting the heterogeneity of ATD."} {"id": "PMID:1282413", "title": "[Higher forms of brain activity and psychology].", "content": "On the examples of comparison of the evoked potentials with a theory of signal identification (A. M. Ivanitsky) and need-informational theory of emotions (P. V. Simonov) with the \"general law of human emotions\" (D. Price, J. Barrell) the efficiency is demonstrated of the simultaneous study of the higher brain functions by neurophysiological and psychological methods. Recent experimental data are given on the natural-scientific bases of consciousness. Human personality is considered as an individual unique composition and internal hierarchy of his vital, social and individual needs. Acknowledgement of the supplementary nature of the objective and subjective analysis of the human behavior helps eliminate the contradiction between the determinism and subjectively sensed freedom of choice.", "contents": "[Higher forms of brain activity and psychology]. On the examples of comparison of the evoked potentials with a theory of signal identification (A. M. Ivanitsky) and need-informational theory of emotions (P. V. Simonov) with the \"general law of human emotions\" (D. Price, J. Barrell) the efficiency is demonstrated of the simultaneous study of the higher brain functions by neurophysiological and psychological methods. Recent experimental data are given on the natural-scientific bases of consciousness. Human personality is considered as an individual unique composition and internal hierarchy of his vital, social and individual needs. Acknowledgement of the supplementary nature of the objective and subjective analysis of the human behavior helps eliminate the contradiction between the determinism and subjectively sensed freedom of choice."} {"id": "PMID:1282414", "title": "[Clinical and genetic studies of Alzheimer-type dementia].", "content": "The families of 128 probands with Alzheimer's disease (AD) and senile dementia (SD) were studied. Genetical and mathematical analyses were employed to estimate the clinico-genealogical findings. The genetic factors were found to be likely to make some contribution to the origin of Alzheimer-type dementia (ATD). The proportion of afflicted relatives considerably exceeded that of the above dementia patients. Two genetic models (monogenic and multifactorial) were tested. The limit estimations of genetic similarity between AD and SD manifestations both in the monogenic and multifactorial models denied the fact that there is a common major gene responsible for liability to Alzheimer-type dementias. The common gene modifiers were assumed to exist in AD and SD. In addition to the differences found between the types of inheritance in patients with these disease, the following features are: an oligogenic type of inheritance in SD and a quasi-dominant one with incomplete manifestations of homo- and heterozygotes in AD. Studies into the clinical polymorphism of Alzheimer-type dementias in hereditary cases enabled the authors to establish the genetically determined signs and the environmentally induced signs. The predisposing features (premorbid characteristic traits and specific features of mnemic and intelligence) were identified, which allowed the development of Alzheimer-type dementias to be predicted in 80% of women from hereditarily aggravated families.", "contents": "[Clinical and genetic studies of Alzheimer-type dementia]. The families of 128 probands with Alzheimer's disease (AD) and senile dementia (SD) were studied. Genetical and mathematical analyses were employed to estimate the clinico-genealogical findings. The genetic factors were found to be likely to make some contribution to the origin of Alzheimer-type dementia (ATD). The proportion of afflicted relatives considerably exceeded that of the above dementia patients. Two genetic models (monogenic and multifactorial) were tested. The limit estimations of genetic similarity between AD and SD manifestations both in the monogenic and multifactorial models denied the fact that there is a common major gene responsible for liability to Alzheimer-type dementias. The common gene modifiers were assumed to exist in AD and SD. In addition to the differences found between the types of inheritance in patients with these disease, the following features are: an oligogenic type of inheritance in SD and a quasi-dominant one with incomplete manifestations of homo- and heterozygotes in AD. Studies into the clinical polymorphism of Alzheimer-type dementias in hereditary cases enabled the authors to establish the genetically determined signs and the environmentally induced signs. The predisposing features (premorbid characteristic traits and specific features of mnemic and intelligence) were identified, which allowed the development of Alzheimer-type dementias to be predicted in 80% of women from hereditarily aggravated families."} {"id": "PMID:1282415", "title": "[Neuromorphology and neurochemistry of senile dementias in the light of studies on glial response].", "content": "The present study describes a few morphological and neurochemical disturbances in astroglial cells in senile dementia of the Alzheimer type (SDAT). The greatly elevated number of fibrous astrocytes in brain samples with SDAT is observed. The content of glial fibrillar acid protein is elevated in these cells. Glial filaments are detected to surround lipid centers. Moreover, there are deviations in energy metabolism: a profound decrease in the levels of the brain creatine kinase CKBB that is one of the principle ATP-regulation enzyme. It is suggested that there is a relationship between all the disturbances observed in glial cells of SDAT patients. These disturbances are likely to be links of the same process which leads to abnormal brain ageing.", "contents": "[Neuromorphology and neurochemistry of senile dementias in the light of studies on glial response]. The present study describes a few morphological and neurochemical disturbances in astroglial cells in senile dementia of the Alzheimer type (SDAT). The greatly elevated number of fibrous astrocytes in brain samples with SDAT is observed. The content of glial fibrillar acid protein is elevated in these cells. Glial filaments are detected to surround lipid centers. Moreover, there are deviations in energy metabolism: a profound decrease in the levels of the brain creatine kinase CKBB that is one of the principle ATP-regulation enzyme. It is suggested that there is a relationship between all the disturbances observed in glial cells of SDAT patients. These disturbances are likely to be links of the same process which leads to abnormal brain ageing."} {"id": "PMID:1282416", "title": "[EEG-mapping in Alzheimer-type dementias].", "content": "EEG topographic correlates of the severity and type of Alzheimer-type dementias have been studied in 21 patients with senile dementia (SD) and 18 with Alzheimer's disease (AD) who were subdivided into smaller groups by MMSE grades for the severity of dementia, as well as in 15 mentally normal elderly persons. EEC maps in SD and AD patients differed from those in normal subjects in increased theta-delta EEG spectral power and suppressed alpha-band power that was more pronounced in the left hemisphere in AD than in SD patients. AD and SD patients had also different EEG topographical changes with intensified cognitive dysfunctions. The results suggest that there is a great cholinergic deficiency and cortical rather than subcortical impairments in patients with AD than in those with SD.", "contents": "[EEG-mapping in Alzheimer-type dementias]. EEG topographic correlates of the severity and type of Alzheimer-type dementias have been studied in 21 patients with senile dementia (SD) and 18 with Alzheimer's disease (AD) who were subdivided into smaller groups by MMSE grades for the severity of dementia, as well as in 15 mentally normal elderly persons. EEC maps in SD and AD patients differed from those in normal subjects in increased theta-delta EEG spectral power and suppressed alpha-band power that was more pronounced in the left hemisphere in AD than in SD patients. AD and SD patients had also different EEG topographical changes with intensified cognitive dysfunctions. The results suggest that there is a great cholinergic deficiency and cortical rather than subcortical impairments in patients with AD than in those with SD."} {"id": "PMID:1282417", "title": "[Computerized tomography approaches in the study of dementia].", "content": "Computed tomography was used to study the prevalence rates of various types of intracranial pathology, hydrocephalus (HDC) and cortical atrophy (CA) in patients with late dementia (LD) and to comparatively assess the informative value of tomographic methods of cerebral morphometry. Computed tomographic data were obtained from 432 patients with LD. Despite the type of dementia, the authors revealed intracranial abnormalities of various etiology in 24.5%, postischemic foci being prevalent. Tumors, arachnoidal cysts, and chronic subdural hematomas were more infrequently diagnosed (in 2.6% of cases). HDC and CA were detected in 81.5 and 82.2% of patients with LD, respectively.", "contents": "[Computerized tomography approaches in the study of dementia]. Computed tomography was used to study the prevalence rates of various types of intracranial pathology, hydrocephalus (HDC) and cortical atrophy (CA) in patients with late dementia (LD) and to comparatively assess the informative value of tomographic methods of cerebral morphometry. Computed tomographic data were obtained from 432 patients with LD. Despite the type of dementia, the authors revealed intracranial abnormalities of various etiology in 24.5%, postischemic foci being prevalent. Tumors, arachnoidal cysts, and chronic subdural hematomas were more infrequently diagnosed (in 2.6% of cases). HDC and CA were detected in 81.5 and 82.2% of patients with LD, respectively."} {"id": "PMID:1282418", "title": "[Comparative analysis of indicators of the immune status of population of the Eastern regions of the USSR].", "content": "Altogether 1,500 healthy residents of seven cities situated in the Asian part of the USSR were examined. In Novosibirsk, Tomsk, Tyumen, Norilsk, Magadan, Yakutsk and Ussuriisk, the people were examined for the blood levels of T and B lymphocytes, the ratio of regulatory subclasses of T lymphocytes, the concentration of IgG, IgM and IgA, and for the content of immune complexes. Analysis was made of the general and regional regularities in changes seen in the immune system depending on climatic and geographic factors. Parameters of the populations similarity in the regions with different environmental conditions were delineated.", "contents": "[Comparative analysis of indicators of the immune status of population of the Eastern regions of the USSR]. Altogether 1,500 healthy residents of seven cities situated in the Asian part of the USSR were examined. In Novosibirsk, Tomsk, Tyumen, Norilsk, Magadan, Yakutsk and Ussuriisk, the people were examined for the blood levels of T and B lymphocytes, the ratio of regulatory subclasses of T lymphocytes, the concentration of IgG, IgM and IgA, and for the content of immune complexes. Analysis was made of the general and regional regularities in changes seen in the immune system depending on climatic and geographic factors. Parameters of the populations similarity in the regions with different environmental conditions were delineated."} {"id": "PMID:1282420", "title": "[Physiological significance of gastroduodenal blood flow and possibilities of its regulation by drugs].", "content": "The authors review the role of the gastroduodenal blood flow as a factor ensuring the secretory activity and protective properties of the gastric mucosa. The possibilities of its pharmacoregulation are also reviewed. It has been shown that the decrease of the gastric blood flow in experimental hemorrhagic shock, extravasal celiac artery stenosis, effects of indomethacin, vasopressin, etc. leads to ischemic injuries to the gastric mucosa accompanied by serious morphological and functional disturbances. The pathogenetic aspects of ischemic injuries to the stomach and duodenum are confirmed by the results of clinical examinations of patients with compression celiac artery stenosis and peptic ulcer. It has been noted that in these patients, the tissue blood flow in the mucosa in considerably decreased in the area of ulcerous defect. The lowering of the content of total phospholipids and changes in their composition were also observed both in relapse and after healing. Out of agents that improve peripheral circulation, propranolol, tavegil combined with cimetidine, trimin appeared most potent. These drugs regulate metabolic processes in gastric tissue, normalizing blood flow, reducing the content of histamine, serotonin, lipid peroxidation products, raising the level of total phospholipids and pepsin.", "contents": "[Physiological significance of gastroduodenal blood flow and possibilities of its regulation by drugs]. The authors review the role of the gastroduodenal blood flow as a factor ensuring the secretory activity and protective properties of the gastric mucosa. The possibilities of its pharmacoregulation are also reviewed. It has been shown that the decrease of the gastric blood flow in experimental hemorrhagic shock, extravasal celiac artery stenosis, effects of indomethacin, vasopressin, etc. leads to ischemic injuries to the gastric mucosa accompanied by serious morphological and functional disturbances. The pathogenetic aspects of ischemic injuries to the stomach and duodenum are confirmed by the results of clinical examinations of patients with compression celiac artery stenosis and peptic ulcer. It has been noted that in these patients, the tissue blood flow in the mucosa in considerably decreased in the area of ulcerous defect. The lowering of the content of total phospholipids and changes in their composition were also observed both in relapse and after healing. Out of agents that improve peripheral circulation, propranolol, tavegil combined with cimetidine, trimin appeared most potent. These drugs regulate metabolic processes in gastric tissue, normalizing blood flow, reducing the content of histamine, serotonin, lipid peroxidation products, raising the level of total phospholipids and pepsin."} {"id": "PMID:1282421", "title": "[Current aspects of the search of effective nootropic drugs].", "content": "The authors review different mechanisms of mnemotropic and cerebroprotective effects of nootropic drugs. The data concerning the molecular mechanisms of action of the structural analogs of the memory stimulant ethylnorantifeine (etimizol) have been summarized and analyzed. It is shown that the effects of antifeines on the retention of the conditioned reflexes are independent of their effects on the cAMP system and structural-functional condition of the neuronal membrane. The key role in the action of these compounds on the long-term memory is played by the activity of the genetic apparatus. The existence of nootropic receptors in neuronal chromatin is assumed.", "contents": "[Current aspects of the search of effective nootropic drugs]. The authors review different mechanisms of mnemotropic and cerebroprotective effects of nootropic drugs. The data concerning the molecular mechanisms of action of the structural analogs of the memory stimulant ethylnorantifeine (etimizol) have been summarized and analyzed. It is shown that the effects of antifeines on the retention of the conditioned reflexes are independent of their effects on the cAMP system and structural-functional condition of the neuronal membrane. The key role in the action of these compounds on the long-term memory is played by the activity of the genetic apparatus. The existence of nootropic receptors in neuronal chromatin is assumed."} {"id": "PMID:1282422", "title": "[Computed cluster analysis of citations as a tool in studying structures of research trends].", "content": "The method of computer cluster-analysis of citation to determine the structure of a scientific trend is suggested. The map of the current status of research in neurobiology of aging as one of the most promising research areas in gerontology is under consideration. The possibilities and perspectives of this method as a tool of science-of-science research in medicine are analyzed.", "contents": "[Computed cluster analysis of citations as a tool in studying structures of research trends]. The method of computer cluster-analysis of citation to determine the structure of a scientific trend is suggested. The map of the current status of research in neurobiology of aging as one of the most promising research areas in gerontology is under consideration. The possibilities and perspectives of this method as a tool of science-of-science research in medicine are analyzed."} {"id": "PMID:1282423", "title": "[Ways of prolonging the action of neuropeptide].", "content": "The paper presents a review of main ways for prolonging the action of neuroregulators (neuropeptides). The method of long-term inverse immunoregulation of immunoregulator levels is regarded as one of the most effective.", "contents": "[Ways of prolonging the action of neuropeptide]. The paper presents a review of main ways for prolonging the action of neuroregulators (neuropeptides). The method of long-term inverse immunoregulation of immunoregulator levels is regarded as one of the most effective."} {"id": "PMID:1282425", "title": "Cytoskeleton of podocytes in vertebrate animals and human.", "content": "Using TEM and immunofluorescence microscope, a study was made on podocytes in vertebrates where an intermediate-sized filament system is replaced by a microtubule system, accompanied by highly developed microfilaments structures. A comparative immunofluorescence study was carried out on cryotome renal sections of plaice (Pleuronectes platessa L.) and rats, using specific antibodies anti-cytokeratins and anti-vimentin. With polyclonal anti-vimentin serum the capillaries of the renal glomeruli showed a bright colour of plaice and only a week one in the rats. Double staining of renal tissue of mongrel rats of different ages (6-7 weeks and 1.8 years old) with antibodies for actin and anti-vimentin polyclonal serum revealed in young rats an intensive fluorescence for actin and a slight fluorescence for the intermediate filaments. Renal glomeruli of old rats demonstrate a strong vimentin-activity and lower actin one. The ultrastructural study of human podocytes showed two different cytoskeleton age-depending types (2, 4, 6, 37 and 65 years old). It is suggested that during individual development and ageing in kidneys of higher animals and human, physiological changes induce morphological cytoskeleton restructuration accompanied by intensive development of intermediate filaments and simultaneous \"involution\" of microtubules and microfilaments.", "contents": "Cytoskeleton of podocytes in vertebrate animals and human. Using TEM and immunofluorescence microscope, a study was made on podocytes in vertebrates where an intermediate-sized filament system is replaced by a microtubule system, accompanied by highly developed microfilaments structures. A comparative immunofluorescence study was carried out on cryotome renal sections of plaice (Pleuronectes platessa L.) and rats, using specific antibodies anti-cytokeratins and anti-vimentin. With polyclonal anti-vimentin serum the capillaries of the renal glomeruli showed a bright colour of plaice and only a week one in the rats. Double staining of renal tissue of mongrel rats of different ages (6-7 weeks and 1.8 years old) with antibodies for actin and anti-vimentin polyclonal serum revealed in young rats an intensive fluorescence for actin and a slight fluorescence for the intermediate filaments. Renal glomeruli of old rats demonstrate a strong vimentin-activity and lower actin one. The ultrastructural study of human podocytes showed two different cytoskeleton age-depending types (2, 4, 6, 37 and 65 years old). It is suggested that during individual development and ageing in kidneys of higher animals and human, physiological changes induce morphological cytoskeleton restructuration accompanied by intensive development of intermediate filaments and simultaneous \"involution\" of microtubules and microfilaments."} {"id": "PMID:1282426", "title": "Biochemical evidence associating membrane-encapsidated particles with reverse transcription in human gastric cancer.", "content": "We provide biochemical evidence demonstrating that membrane encapsidated structures present in terminal gastric patients share similar features with retrovirus-like particles. Purified particles reveal few polypeptides, one of them glycosylated. A ribonucleoprotein core-like component is recovered which retains the DNA-polymerizing activity and contains at least one RNA component which can be efficiently translated in vitro.", "contents": "Biochemical evidence associating membrane-encapsidated particles with reverse transcription in human gastric cancer. We provide biochemical evidence demonstrating that membrane encapsidated structures present in terminal gastric patients share similar features with retrovirus-like particles. Purified particles reveal few polypeptides, one of them glycosylated. A ribonucleoprotein core-like component is recovered which retains the DNA-polymerizing activity and contains at least one RNA component which can be efficiently translated in vitro."} {"id": "PMID:1282427", "title": "Immunostaining of nucleolus organizers in mammalian cells by a human autoantibody against the polymerase I transcription factor UBF.", "content": "A mammalian autoantigen of the nucleolus organizing regions (NORs) was identified by a human autoantibody from the serum of a rheumatoid arthritis patient. The distribution and changes of NORs during the cell cycle of mammals were followed by using this autoantiserum in indirect-immunofluorescence microscopy. In interphase cells the staining pattern indicated that the autoantigen is restricted exclusively within the nucleolus. This fluorescence appeared punctuated rather than uniform, and it was reorganized during inhibition of transcription in cells treated with actinomycin D. During mitosis, the autoantigen was detected by light microscopy at the chromosomal nucleolus organizer regions, indicating that presumably the protein remains bound to the rRNA genes. Biochemical analysis by immunoblotting showed that the NOR autoantigen consists of two polypeptides with molecular masses apparent of 90-92 kDa in all of the mammalian cell lines tested. The identity of some epitopes, recognized by this autoantibody as the ribosomal transcription factor UBF, is discussed.", "contents": "Immunostaining of nucleolus organizers in mammalian cells by a human autoantibody against the polymerase I transcription factor UBF. A mammalian autoantigen of the nucleolus organizing regions (NORs) was identified by a human autoantibody from the serum of a rheumatoid arthritis patient. The distribution and changes of NORs during the cell cycle of mammals were followed by using this autoantiserum in indirect-immunofluorescence microscopy. In interphase cells the staining pattern indicated that the autoantigen is restricted exclusively within the nucleolus. This fluorescence appeared punctuated rather than uniform, and it was reorganized during inhibition of transcription in cells treated with actinomycin D. During mitosis, the autoantigen was detected by light microscopy at the chromosomal nucleolus organizer regions, indicating that presumably the protein remains bound to the rRNA genes. Biochemical analysis by immunoblotting showed that the NOR autoantigen consists of two polypeptides with molecular masses apparent of 90-92 kDa in all of the mammalian cell lines tested. The identity of some epitopes, recognized by this autoantibody as the ribosomal transcription factor UBF, is discussed."} {"id": "PMID:1282428", "title": "Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements.", "content": "We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19+ cells were < 25% and the ratio of CD5 + CD19 + /CD19 + cells was < 25%. According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases.", "contents": "Evaluation of residual disease in B-cell chronic lymphocytic leukemia patients in clinical and bone-marrow remission using CD5-CD19 markers and PCR study of gene rearrangements. We evaluated minimal residual disease (MRD) in 23 CD5 + B-chronic lymphocytic leukemia (CLL) patients who achieved clinico-hematological remission confirmed by bone-marrow biopsy. MRD was evaluated by dual marker analysis flow-cytometry using CD5 and CD19 markers, and by the study of Ig heavy chain gene rearrangements using the fast polymerase chain reaction (PCR). According to our laboratory conditions patients were considered to be in complete phenotypic remission when total CD19+ cells were < 25% and the ratio of CD5 + CD19 + /CD19 + cells was < 25%. According to these strict criteria only 9 of the 23 patients were in complete phenotypic remission. In order to evaluate the sensitivity of the above method, PCR analysis of the configuration of the Ig heavy chain gene region was performed in 12 of these patients. Five of 7 patients in complete phenotypic remission retained a detectable monoclonal rearrangement of the Ig heavy chain gene. For the remaining 5 patients in partial phenotypic remission, only one failed to show a monoclonal band and this is probably explained by the presence of an unusual gene rearrangement. In conclusion, this study suggests that PCR is more sensitive than dual marker flow-cytometry for evaluation of residual disease and that it is indeed possible to achieve complete remission at the molecular level, in B-CLL. Nevertheless, we suggest a word of caution as this was a retrospective study, and samples were not assessed before treatment. Thus the possibility that apparent molecular remission might correspond to unusual gene rearrangements cannot be completely excluded in these cases."} {"id": "PMID:1282429", "title": "Right ventricular outflow tract obstruction due to extrinsic compression by non-Hodgkin's lymphoma: importance of echocardiographic diagnosis and follow up.", "content": "Acquired right ventricular outflow tract obstruction due to extrinsic compression of the pulmonary artery is a rare manifestation of non-Hodgkin's lymphoma (NHL). We report a case of a 17 year old boy who was referred for evaluation of a large anterior mediastinal mass, causing dyspnea and cough and resulting in a harsh systolic murmur. Echocardiography demonstrated compression of the pulmonary artery by the mass, with a severe pressure gradient. Biopsy revealed intermediate grade, diffuse large cell NHL. Systemic chemotherapy rapidly led to a significant decrease in the size of the mass, and virtual disappearance of the pressure gradient. In this report, the use of echocardiography for diagnosis and follow up of extracardiac tumors is reviewed. It is suggested that this technique may also be useful for the routine staging of mediastinal lymphomas because of the potential consequences of clinically undetectable hemodynamic compromise.", "contents": "Right ventricular outflow tract obstruction due to extrinsic compression by non-Hodgkin's lymphoma: importance of echocardiographic diagnosis and follow up. Acquired right ventricular outflow tract obstruction due to extrinsic compression of the pulmonary artery is a rare manifestation of non-Hodgkin's lymphoma (NHL). We report a case of a 17 year old boy who was referred for evaluation of a large anterior mediastinal mass, causing dyspnea and cough and resulting in a harsh systolic murmur. Echocardiography demonstrated compression of the pulmonary artery by the mass, with a severe pressure gradient. Biopsy revealed intermediate grade, diffuse large cell NHL. Systemic chemotherapy rapidly led to a significant decrease in the size of the mass, and virtual disappearance of the pressure gradient. In this report, the use of echocardiography for diagnosis and follow up of extracardiac tumors is reviewed. It is suggested that this technique may also be useful for the routine staging of mediastinal lymphomas because of the potential consequences of clinically undetectable hemodynamic compromise."} {"id": "PMID:1282430", "title": "PCR-mediated cloning of HpaII tiny fragments from microdissected human chromosomes.", "content": "Vertebrate DNA contains a small fraction of unmethylated CpG-rich DNA sequences, many of which include the 5' end of a gene. This fraction can be detected by its cleavage to tiny fragments with the methylation-sensitive restriction enzyme HpaII. Thus, the isolation of HpaII tiny fragments (HTFs) from a specific chromosome region may be a useful approach for making an inventory of the genes contained in it. Using microdissection, we have isolated DNA from human chromosome band 8q24.1. The DNA was digested with HpaII, ligated to a ClaI-cut pUC plasmid, and amplified with Taq DNA polymerase and the standard M13/pUC forward and reverse sequencing primers. The amplification products were used to construct an HTF library, which is enriched for CpG-rich single-copy clones.", "contents": "PCR-mediated cloning of HpaII tiny fragments from microdissected human chromosomes. Vertebrate DNA contains a small fraction of unmethylated CpG-rich DNA sequences, many of which include the 5' end of a gene. This fraction can be detected by its cleavage to tiny fragments with the methylation-sensitive restriction enzyme HpaII. Thus, the isolation of HpaII tiny fragments (HTFs) from a specific chromosome region may be a useful approach for making an inventory of the genes contained in it. Using microdissection, we have isolated DNA from human chromosome band 8q24.1. The DNA was digested with HpaII, ligated to a ClaI-cut pUC plasmid, and amplified with Taq DNA polymerase and the standard M13/pUC forward and reverse sequencing primers. The amplification products were used to construct an HTF library, which is enriched for CpG-rich single-copy clones."} {"id": "PMID:1282431", "title": "Detection and identification of multiple mycobacterial pathogens by DNA amplification in a single tube.", "content": "A comparison of the DNA sequence of the 16S rRNA revealed a region in which there was a minor variation between the species of mycobacteria. This information was used to develop a multiplex amplification system that could identify the genus Mycobacterium and then distinguish between M. avium and M. intracellulare, two commonly encountered mycobacteria other than tuberculosis. The combination of these rRNA gene primers together with primers aimed at the MPB70 gene of M. tuberculosis complex organisms permits the detection and identification of clinically significant mycobacteria in a single tube. An amplification product of 1030 bp is indicative of the genus Mycobacterium and smaller fragments of 850, 372, and 180 bp are the positive signals for M. intracellulare, M. tuberculosis complex, and M. avium, respectively.", "contents": "Detection and identification of multiple mycobacterial pathogens by DNA amplification in a single tube. A comparison of the DNA sequence of the 16S rRNA revealed a region in which there was a minor variation between the species of mycobacteria. This information was used to develop a multiplex amplification system that could identify the genus Mycobacterium and then distinguish between M. avium and M. intracellulare, two commonly encountered mycobacteria other than tuberculosis. The combination of these rRNA gene primers together with primers aimed at the MPB70 gene of M. tuberculosis complex organisms permits the detection and identification of clinically significant mycobacteria in a single tube. An amplification product of 1030 bp is indicative of the genus Mycobacterium and smaller fragments of 850, 372, and 180 bp are the positive signals for M. intracellulare, M. tuberculosis complex, and M. avium, respectively."} {"id": "PMID:1282436", "title": "In situ localization of PCR-amplified human and viral cDNAs.", "content": "We describe a technique, called reverse transcriptase (RT) in situ PCR, whereby RNA may be nonisotopically detected in fixed cells when amplified by PCR after cDNA synthesis by RT. RT in situ PCR using primers specific for the measles virus generated an intense signal in most measles-infected HeLa cells, as compared to the weak signal generated in few cells using standard in situ hybridization analysis. The viral RNA that localized to the nucleus spared the nucleoli, was most evident when the RT step used the primer complementary to the negative genomic strand, and was demonstrated in all multinucleated cells and the majority of uninucleate cells. A hybridization signal was evident with standard RNA in situ hybridization using the human megakaryocyte cell line Dami and a probe for glycoprotein IIB (GIIB) mRNA but not a probe for amyloid precursor protein (APP) or gelsolin (GEL) mRNA. After RT in situ PCR, signals were evident for each target localizing to the nucleolus for APP and to perinucleolar and cytoplasmic locations for GEL and GIIB. The latter findings suggest that mRNAs may follow different geographic pathways as they progress from premessage to transcriptionally active message.", "contents": "In situ localization of PCR-amplified human and viral cDNAs. We describe a technique, called reverse transcriptase (RT) in situ PCR, whereby RNA may be nonisotopically detected in fixed cells when amplified by PCR after cDNA synthesis by RT. RT in situ PCR using primers specific for the measles virus generated an intense signal in most measles-infected HeLa cells, as compared to the weak signal generated in few cells using standard in situ hybridization analysis. The viral RNA that localized to the nucleus spared the nucleoli, was most evident when the RT step used the primer complementary to the negative genomic strand, and was demonstrated in all multinucleated cells and the majority of uninucleate cells. A hybridization signal was evident with standard RNA in situ hybridization using the human megakaryocyte cell line Dami and a probe for glycoprotein IIB (GIIB) mRNA but not a probe for amyloid precursor protein (APP) or gelsolin (GEL) mRNA. After RT in situ PCR, signals were evident for each target localizing to the nucleolus for APP and to perinucleolar and cytoplasmic locations for GEL and GIIB. The latter findings suggest that mRNAs may follow different geographic pathways as they progress from premessage to transcriptionally active message."} {"id": "PMID:1282437", "title": "Development of a sensitive reverse transcriptase PCR assay, RT-RPCR, utilizing rapid cycle times.", "content": "We describe a procedure to analyze rare gene transcripts quantitatively using a reverse transcriptase-polymerase chain (RT-PCR) reaction. RNA purified from cells and tissues is reverse-transcribed using random hexamer primers and is amplified using very short cycle times. The products are trace-labeled with [32P[dCTP, which allows for the quantitation of the products by gel electrophoresis and excision of bands. The quantity of the PCR product is directly proportional to the quantity of cDNA added and is reproducible from a single cDNA preparation or from samples derived from separate preparations. Because cDNA synthesis is primed with random oligonucleotides, the same cDNA sample preparation can be examined for many different gene products.", "contents": "Development of a sensitive reverse transcriptase PCR assay, RT-RPCR, utilizing rapid cycle times. We describe a procedure to analyze rare gene transcripts quantitatively using a reverse transcriptase-polymerase chain (RT-PCR) reaction. RNA purified from cells and tissues is reverse-transcribed using random hexamer primers and is amplified using very short cycle times. The products are trace-labeled with [32P[dCTP, which allows for the quantitation of the products by gel electrophoresis and excision of bands. The quantity of the PCR product is directly proportional to the quantity of cDNA added and is reproducible from a single cDNA preparation or from samples derived from separate preparations. Because cDNA synthesis is primed with random oligonucleotides, the same cDNA sample preparation can be examined for many different gene products."} {"id": "PMID:1282441", "title": "[Secretory meningioma].", "content": "Pseudopsammomatous inclusions were found in two cases of secretory meningioma. Their description includes ultrastructural and immunohistochemical features.", "contents": "[Secretory meningioma]. Pseudopsammomatous inclusions were found in two cases of secretory meningioma. Their description includes ultrastructural and immunohistochemical features."} {"id": "PMID:1282442", "title": "Effect of bredinin on the primary culture of fetal mouse cells and adult mouse lung cells.", "content": "The effects of bredinin on the primary culture of fetal mouse cells (fetal cells) and adult mouse lung cells (lung cells) were compared. Bredinin inhibited the growth of both cells, and this inhibition was found to be caused, at least in part, by the inhibition of the S phase and/or the transition from the G1 to S phase of the cell cycle. Bredinin inhibited both DNA and RNA synthesis without affecting protein synthesis. However, the inhibitory effect of bredinin differed between the two cell lines; the fetal cells were more sensitive than the lung cells, and bredinin inhibited DNA synthesis 100 times more potently in the fetal cells. The inhibition of DNA synthesis by bredinin in the fetal cells was gradually lowered by in vitro aging of the fetal cells to a level similar to that in the lung cells. There was no difference in the rate of incorporation of bredinin into the cells between the fetal cells and the lung cells. When fetal tissue was used as an enzyme source, bredinin was converted to bredinin 5'-monophosphate (BMP), but when lung tissue was used, bredinin was not converted. This is in agreement with the finding that bredinin has selective toxicity on fetuses in vivo but is hardly toxic to adult cells, which suggests the involvement of BMP in the selective toxicity of bredinin on the fetus.", "contents": "Effect of bredinin on the primary culture of fetal mouse cells and adult mouse lung cells. The effects of bredinin on the primary culture of fetal mouse cells (fetal cells) and adult mouse lung cells (lung cells) were compared. Bredinin inhibited the growth of both cells, and this inhibition was found to be caused, at least in part, by the inhibition of the S phase and/or the transition from the G1 to S phase of the cell cycle. Bredinin inhibited both DNA and RNA synthesis without affecting protein synthesis. However, the inhibitory effect of bredinin differed between the two cell lines; the fetal cells were more sensitive than the lung cells, and bredinin inhibited DNA synthesis 100 times more potently in the fetal cells. The inhibition of DNA synthesis by bredinin in the fetal cells was gradually lowered by in vitro aging of the fetal cells to a level similar to that in the lung cells. There was no difference in the rate of incorporation of bredinin into the cells between the fetal cells and the lung cells. When fetal tissue was used as an enzyme source, bredinin was converted to bredinin 5'-monophosphate (BMP), but when lung tissue was used, bredinin was not converted. This is in agreement with the finding that bredinin has selective toxicity on fetuses in vivo but is hardly toxic to adult cells, which suggests the involvement of BMP in the selective toxicity of bredinin on the fetus."} {"id": "PMID:1282440", "title": "Immunosuppressive drugs.", "content": "The success rate of clinical transplantation has improved considerably over the last two decades largely due to better immunosuppressive drugs. Allograft rejection remains the major cause of graft loss in renal transplant recipients. This article reviews the mechanisms of action of immunosuppressive drugs and their clinical use.", "contents": "Immunosuppressive drugs. The success rate of clinical transplantation has improved considerably over the last two decades largely due to better immunosuppressive drugs. Allograft rejection remains the major cause of graft loss in renal transplant recipients. This article reviews the mechanisms of action of immunosuppressive drugs and their clinical use."} {"id": "PMID:1282443", "title": "Macromolecule-macromolecule interaction in drug distribution. II. Effect of alpha-globulin on saturable uptake of fractionated [3H]heparin by rat parenchymal hepatocytes in primary culture.", "content": "The uptake of fractionated [3H]heparin was investigated in rat parenchymal hepatocytes in primary culture. The initial uptake of fractionated [3H]heparin was found to be saturable with the maximum uptake velocity (Vmax) of 10.1 +/- 1.46 pmol/min/mg protein and the Michaelis constant (Km) of 284 +/- 47.9 nM. The effect of alpha-globulin, the major protein binding to fractionated [3H]heparin, on the saturable uptake profile of fractionated [3H]heparin was also investigated. The uptake clearance was reduced, depending on the concentration of fractionated [3H]heparin, by the addition of 1 mg/ml alpha-globulin. We assumed that fractionated 3H-heparin bound to alpha-globulin was not available for uptake and that the reduction in the uptake clearance was solely attributable to the saturable binding of fractionated [3H]heparin to alpha-globulin. The uptake clearance versus concentration profile was analyzed to obtain the dissociation constant (Kd) of 31.8 nM and the capacity (n) of 0.047 for the binding of fractionated [3H]heparin to alpha-globulin. The saturable binding of fractionated [3H]heparin to alpha-globulin was supported by in vitro binding experiments using gel chromatography, in which bound fractionated [3H]heparin decreased with the concentration of fractionated [3H]heparin in the presence of alpha-globulin. In conclusion, the present study demonstrated the saturable uptake of fractionated [3H]heparin by rat parenchymal hepatocytes and the saturable binding of fractionated [3H]heparin to alpha-globulin. The saturable uptake may suggest the involvement of a specific transport system such as receptor-mediated endocytosis.", "contents": "Macromolecule-macromolecule interaction in drug distribution. II. Effect of alpha-globulin on saturable uptake of fractionated [3H]heparin by rat parenchymal hepatocytes in primary culture. The uptake of fractionated [3H]heparin was investigated in rat parenchymal hepatocytes in primary culture. The initial uptake of fractionated [3H]heparin was found to be saturable with the maximum uptake velocity (Vmax) of 10.1 +/- 1.46 pmol/min/mg protein and the Michaelis constant (Km) of 284 +/- 47.9 nM. The effect of alpha-globulin, the major protein binding to fractionated [3H]heparin, on the saturable uptake profile of fractionated [3H]heparin was also investigated. The uptake clearance was reduced, depending on the concentration of fractionated [3H]heparin, by the addition of 1 mg/ml alpha-globulin. We assumed that fractionated 3H-heparin bound to alpha-globulin was not available for uptake and that the reduction in the uptake clearance was solely attributable to the saturable binding of fractionated [3H]heparin to alpha-globulin. The uptake clearance versus concentration profile was analyzed to obtain the dissociation constant (Kd) of 31.8 nM and the capacity (n) of 0.047 for the binding of fractionated [3H]heparin to alpha-globulin. The saturable binding of fractionated [3H]heparin to alpha-globulin was supported by in vitro binding experiments using gel chromatography, in which bound fractionated [3H]heparin decreased with the concentration of fractionated [3H]heparin in the presence of alpha-globulin. In conclusion, the present study demonstrated the saturable uptake of fractionated [3H]heparin by rat parenchymal hepatocytes and the saturable binding of fractionated [3H]heparin to alpha-globulin. The saturable uptake may suggest the involvement of a specific transport system such as receptor-mediated endocytosis."} {"id": "PMID:1282444", "title": "Induction of the blood-brain barrier specific HT7 and neurothelin epitopes in endothelial cells of the chick chorioallantoic vessels by a soluble factor derived from astrocytes.", "content": "Some blood-brain barrier properties of microvascular endothelial cells have been shown to be inducible by astrocytes. We tested the hypothesis that this cellular interaction is mediated by a soluble factor(s). Chick chorioallantoic vessels in ovo were constantly exposed to astrocyte-conditioned medium. We found that endothelial cells exposed to astrocyte-derived factors, but not to glioma- or endothelial cell-derived factors, expressed the HT7 antigen and neurothelin, two specific markers of the blood-brain barrier phenotype. These results indicate that a soluble factor(s) secreted by astrocytes is capable to induce specific blood-brain barrier properties in endothelial cells of non-neural origin.", "contents": "Induction of the blood-brain barrier specific HT7 and neurothelin epitopes in endothelial cells of the chick chorioallantoic vessels by a soluble factor derived from astrocytes. Some blood-brain barrier properties of microvascular endothelial cells have been shown to be inducible by astrocytes. We tested the hypothesis that this cellular interaction is mediated by a soluble factor(s). Chick chorioallantoic vessels in ovo were constantly exposed to astrocyte-conditioned medium. We found that endothelial cells exposed to astrocyte-derived factors, but not to glioma- or endothelial cell-derived factors, expressed the HT7 antigen and neurothelin, two specific markers of the blood-brain barrier phenotype. These results indicate that a soluble factor(s) secreted by astrocytes is capable to induce specific blood-brain barrier properties in endothelial cells of non-neural origin."} {"id": "PMID:1282446", "title": "Patterns of primary degranulation as indicated by the mean myeloperoxidase index (MPXI) during bacteraemia in lymphoma transplants treated with growth factors.", "content": "The pattern of changes in neutrophil myeloperoxidase (MPO) before, during and after bacteraemia was studied in 34 patients recovering from autologous bone marrow transplantation for relapsed Hodgkin's disease and non Hodgkin's lymphomas. Thirteen patients received haemopoietic growth factors (7 received M-CSF, 3 received G-CSF and 3 GM-CSF). The mean peroxidase index (MPXI) produced as part of a routine FBC performed by a flow cytochemistry blood autoanalyser (Technicon H*1) was used as a parameter to assess the MPO and subsequently the azurophil degranulation. The manufacturer's normal values for MPXI range from -10 to +10. Median MPXI on the day of documented bacteraemia was just below normal in the control and M-CSF groups (-10.8 and -8.9 respectively), but it was much below normal in the G-CSF (-16.5, P < 0.05) and even lower in the GM-CSF group (-39.6, P < 0.02); this correlated well with the decreased bacteraemia incidence in the last two groups. Although contact of neutrophils with bacterial chemoattractants resulted in primary degranulation in all groups, the pattern of changes in MPO content was different, suggesting that neutrophils primed in vivo with various haemopoietins respond to the challenge of microbial agents via different pathways.", "contents": "Patterns of primary degranulation as indicated by the mean myeloperoxidase index (MPXI) during bacteraemia in lymphoma transplants treated with growth factors. The pattern of changes in neutrophil myeloperoxidase (MPO) before, during and after bacteraemia was studied in 34 patients recovering from autologous bone marrow transplantation for relapsed Hodgkin's disease and non Hodgkin's lymphomas. Thirteen patients received haemopoietic growth factors (7 received M-CSF, 3 received G-CSF and 3 GM-CSF). The mean peroxidase index (MPXI) produced as part of a routine FBC performed by a flow cytochemistry blood autoanalyser (Technicon H*1) was used as a parameter to assess the MPO and subsequently the azurophil degranulation. The manufacturer's normal values for MPXI range from -10 to +10. Median MPXI on the day of documented bacteraemia was just below normal in the control and M-CSF groups (-10.8 and -8.9 respectively), but it was much below normal in the G-CSF (-16.5, P < 0.05) and even lower in the GM-CSF group (-39.6, P < 0.02); this correlated well with the decreased bacteraemia incidence in the last two groups. Although contact of neutrophils with bacterial chemoattractants resulted in primary degranulation in all groups, the pattern of changes in MPO content was different, suggesting that neutrophils primed in vivo with various haemopoietins respond to the challenge of microbial agents via different pathways."} {"id": "PMID:1282448", "title": "On the nature of naming difficulties in aphasia.", "content": "An extensive naming battery was administered to ten patients representing classical aphasia syndromes. The battery included traditional performance measures and error scoring, phonological cuing, multiple-choice tasks tapping semantic and phonological knowledge, and word repetition tests. Differences in the patients' performance profiles were interpreted as reflecting lexical-phonological, phoneme assembly or multiple deficits. The results suggest that the hypothesized naming deficits have complex relationships to classical aphasia syndromes.", "contents": "On the nature of naming difficulties in aphasia. An extensive naming battery was administered to ten patients representing classical aphasia syndromes. The battery included traditional performance measures and error scoring, phonological cuing, multiple-choice tasks tapping semantic and phonological knowledge, and word repetition tests. Differences in the patients' performance profiles were interpreted as reflecting lexical-phonological, phoneme assembly or multiple deficits. The results suggest that the hypothesized naming deficits have complex relationships to classical aphasia syndromes."} {"id": "PMID:1282449", "title": "Peculiarities of functioning of protein-synthesizing apparatus of the hibernator (Citellus undulatus).", "content": "Synthesis of proteins and RNA has been studied by means of labeled precursors of 14C-labeled amino acids and [14C]orotic acid in liver cells of hibernating, arousing, and active ground squirrels (Citellus undulatus). The investigations indicate that cycloheximide (CHI)-inhibited protein synthesis in liver cells of hibernating ground squirrels may occur on preexisting polyribosomes. A low level of protein synthesis in this state results not only from the Arrhenius dependence, but also from the dissociation of polyribosomes into monosomes. During arousal there is an intensive assembly of polyribosomes. This occurs even with the inhibition of RNA synthesis by actinomycin D, testifying to the presence of a pool of iRNA in liver cells, which is necessary to activate translation. The intensity of protein synthesis in arousal is also influenced by the activation of transcription.", "contents": "Peculiarities of functioning of protein-synthesizing apparatus of the hibernator (Citellus undulatus). Synthesis of proteins and RNA has been studied by means of labeled precursors of 14C-labeled amino acids and [14C]orotic acid in liver cells of hibernating, arousing, and active ground squirrels (Citellus undulatus). The investigations indicate that cycloheximide (CHI)-inhibited protein synthesis in liver cells of hibernating ground squirrels may occur on preexisting polyribosomes. A low level of protein synthesis in this state results not only from the Arrhenius dependence, but also from the dissociation of polyribosomes into monosomes. During arousal there is an intensive assembly of polyribosomes. This occurs even with the inhibition of RNA synthesis by actinomycin D, testifying to the presence of a pool of iRNA in liver cells, which is necessary to activate translation. The intensity of protein synthesis in arousal is also influenced by the activation of transcription."} {"id": "PMID:1282447", "title": "Evaluation of the Gen-Probe PACE II assay for the direct detection of Neisseria gonorrhoeae in endocervical specimens.", "content": "Evaluation of a non-isotopic DNA-rRNA hybridization assay [Probe Assay-Chemiluminescence Enhanced System (PACE II, Gen-Probe, San Diego, CA)] for the direct detection of Neisseria gonorrhoeae from clinical specimens was compared with culture. Culture and probe tests were performed on 795 endocervical specimens. Results demonstrated that total positives by culture were 18 (2.3% of total); both culture and the DNA-rRNA assay agreed in all cases but four. The PACE II yielded four hybridization-positive results with negative companion cultures. The sensitivity, specificity, and positive and negative predictive values for PACE II were 100%, 99.5%, and 82%, and 100%, respectively. The four discrepant results were resolved using a competitive nucleic acid hybridization assay with recalculated sensitivity, specificity, and positive and negative predictive values of 100, 99.7, and 91.6 and 100%, respectively. Overall, the DNA-rRNA assay offered a number of advantages over culture. The assay was more rapid, able to be performed directly on clinical specimens, and provided superior transport stability.", "contents": "Evaluation of the Gen-Probe PACE II assay for the direct detection of Neisseria gonorrhoeae in endocervical specimens. Evaluation of a non-isotopic DNA-rRNA hybridization assay [Probe Assay-Chemiluminescence Enhanced System (PACE II, Gen-Probe, San Diego, CA)] for the direct detection of Neisseria gonorrhoeae from clinical specimens was compared with culture. Culture and probe tests were performed on 795 endocervical specimens. Results demonstrated that total positives by culture were 18 (2.3% of total); both culture and the DNA-rRNA assay agreed in all cases but four. The PACE II yielded four hybridization-positive results with negative companion cultures. The sensitivity, specificity, and positive and negative predictive values for PACE II were 100%, 99.5%, and 82%, and 100%, respectively. The four discrepant results were resolved using a competitive nucleic acid hybridization assay with recalculated sensitivity, specificity, and positive and negative predictive values of 100, 99.7, and 91.6 and 100%, respectively. Overall, the DNA-rRNA assay offered a number of advantages over culture. The assay was more rapid, able to be performed directly on clinical specimens, and provided superior transport stability."} {"id": "PMID:1282451", "title": "[Detection of serum antibody against hepatitis C virus in patients with hepatitis and liver diseases].", "content": "Antibody against hepatitis C virus (anti-HCV) was tested in 658 cases of hepatitis and liver diseases with ELISA, ninety of these cases were positive, with a total infection rate of 13.68% (90/658). The positive rate of anti-HCV was highest in patients with chronic severe hepatitis (33.78%) and CAH accompanied by cirrhosis of liver(31.58%). The infection rate in other types of hepatic diseases in order of frequency was as follows: fulminant hepatitis (18.18%), CAH without cirrhosis (15.13%), subacute severe hepatitis (13.43%), CPH (5.88%), primary hepatocellular carcinoma (3.85%), and acute hepatitis (2.42%). Serological markers of HBV infection were detectable concomitantly in 77 of the 90 cases who were anti-HCV positive, but there was no evidence of mutual inhibition of viral replication. There was neither appreciable difference in the level of hyperbilirubinemia in cases of hepatitis with or without anti-HCV, nor significant diversity in the number of death between cases of severe hepatitis with and without anti-HCV.", "contents": "[Detection of serum antibody against hepatitis C virus in patients with hepatitis and liver diseases]. Antibody against hepatitis C virus (anti-HCV) was tested in 658 cases of hepatitis and liver diseases with ELISA, ninety of these cases were positive, with a total infection rate of 13.68% (90/658). The positive rate of anti-HCV was highest in patients with chronic severe hepatitis (33.78%) and CAH accompanied by cirrhosis of liver(31.58%). The infection rate in other types of hepatic diseases in order of frequency was as follows: fulminant hepatitis (18.18%), CAH without cirrhosis (15.13%), subacute severe hepatitis (13.43%), CPH (5.88%), primary hepatocellular carcinoma (3.85%), and acute hepatitis (2.42%). Serological markers of HBV infection were detectable concomitantly in 77 of the 90 cases who were anti-HCV positive, but there was no evidence of mutual inhibition of viral replication. There was neither appreciable difference in the level of hyperbilirubinemia in cases of hepatitis with or without anti-HCV, nor significant diversity in the number of death between cases of severe hepatitis with and without anti-HCV."} {"id": "PMID:1282450", "title": "Supportive care in oncology.", "content": "Pain management, nutritional support, and psychosocial support are fundamental services that enhance patients' ability to cope with their cancer and its therapy. The common goal of symptom prevention mandates that each of these supportive services be provided to all patients throughout their cancer experience. Comprehensive cancer pain management begins with identifying the origin of all of the patient's pains and treating each one specifically. Pain prevention can be achieved through around-the-clock opioid administration with as-needed supplements for breakthrough pain and dose titration. Common narcotic side effects such as constipation and nausea also must be prevented. Successful opioid analgesia requires that patient and family concerns regarding addiction and tolerance be dispelled at the outset. Cancer pain prevention can be further optimized with the use of appropriate coanalgesics in response to the pathophysiology of the patient's pains. Cognitive and behavioral therapies may also be useful adjuncts to reduce both pain and suffering. Procedure-oriented pain control should be considered when systemic pharmacologic therapy does not provide adequate pain relief or is associated with intolerable side effects. The only absolute contraindications for pain-relieving procedures are untreatable coagulopathy and a decrease in mental status not related to medical pain management. Useful neurodestructive techniques include radiofrequency lesioning, cryoanalgesia, and chemical neurolysis with agents such as phenol, alcohol, and hypertonic saline. The most beneficial pain-relieving procedures and percutaneous cordotomy, spinal narcotics, celiac and hypogastric plexus ablation, spinal neurolysis, and epidural injection of steroids and hypertonic saline. Procedure selection depends on the cause of the pain and the patient's prognosis. Common indications for pain-relieving procedures include unilateral pain below the shoulder, upper abdominal visceral pains, pelvic visceral pain, perineal pain, vertebral body metastasis, discogenic pain, and spinal stenosis. As results of well-conducted scientific trials begin to appear in the literature, the indications for these procedures will be better understood, resulting in their more appropriate use. Principles of nutritional support in patients with cancer include an awareness of the problem of malnutrition and its impact on performance status, quality of life, prognosis, and treatment; identification of those patients at risk; prophylactic versus therapeutic intervention; and analysis and management of the specific impediment(s) to adequate nutrient intake and absorption. The primary goals for nutritional support in cancer patients are prevention of weight loss and maintenance of adequate protein status. Appreciation of practical issues of nutritional support will enable the practicing physician to achieve these goals using primarily oral nutrition options.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Supportive care in oncology. Pain management, nutritional support, and psychosocial support are fundamental services that enhance patients' ability to cope with their cancer and its therapy. The common goal of symptom prevention mandates that each of these supportive services be provided to all patients throughout their cancer experience. Comprehensive cancer pain management begins with identifying the origin of all of the patient's pains and treating each one specifically. Pain prevention can be achieved through around-the-clock opioid administration with as-needed supplements for breakthrough pain and dose titration. Common narcotic side effects such as constipation and nausea also must be prevented. Successful opioid analgesia requires that patient and family concerns regarding addiction and tolerance be dispelled at the outset. Cancer pain prevention can be further optimized with the use of appropriate coanalgesics in response to the pathophysiology of the patient's pains. Cognitive and behavioral therapies may also be useful adjuncts to reduce both pain and suffering. Procedure-oriented pain control should be considered when systemic pharmacologic therapy does not provide adequate pain relief or is associated with intolerable side effects. The only absolute contraindications for pain-relieving procedures are untreatable coagulopathy and a decrease in mental status not related to medical pain management. Useful neurodestructive techniques include radiofrequency lesioning, cryoanalgesia, and chemical neurolysis with agents such as phenol, alcohol, and hypertonic saline. The most beneficial pain-relieving procedures and percutaneous cordotomy, spinal narcotics, celiac and hypogastric plexus ablation, spinal neurolysis, and epidural injection of steroids and hypertonic saline. Procedure selection depends on the cause of the pain and the patient's prognosis. Common indications for pain-relieving procedures include unilateral pain below the shoulder, upper abdominal visceral pains, pelvic visceral pain, perineal pain, vertebral body metastasis, discogenic pain, and spinal stenosis. As results of well-conducted scientific trials begin to appear in the literature, the indications for these procedures will be better understood, resulting in their more appropriate use. Principles of nutritional support in patients with cancer include an awareness of the problem of malnutrition and its impact on performance status, quality of life, prognosis, and treatment; identification of those patients at risk; prophylactic versus therapeutic intervention; and analysis and management of the specific impediment(s) to adequate nutrient intake and absorption. The primary goals for nutritional support in cancer patients are prevention of weight loss and maintenance of adequate protein status. Appreciation of practical issues of nutritional support will enable the practicing physician to achieve these goals using primarily oral nutrition options.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282452", "title": "Effect of a prostaglandin I2 derivative (iloprost) on peripheral neuropathy of diabetic rats.", "content": "PGE1 has been found to improve the symptoms of diabetic neuropathy. We considered that a PGI2 derivative may also have a similar action and therefore studied its effect in diabetic rats. Iloprost was administered intraperitoneally to streptozotocin-induced diabetic rats at a dose of 10 micrograms/kg/day for a month. The changes in nerve conduction velocity (NCV) were measured in the tail. One day after the last dose of iloprost, both sciatic nerves were removed from each rat, homogenized, and extracted with 6% TCA. The sorbitol and myo-inositol concentrations were determined by a combination of HPLC and an enzymatic method. Cyclic AMP (cAMP) levels were determined by RIA, and Na+, K+ ATPase activity was assessed by the enzyme cycling method of Greene and Lattimer. Iloprost was found to improve the NCV in the diabetic rats. The sorbitol content was not affected by iloprost, but the myo-inositol content was higher in the iloprost group than in the untreated group, although the difference was not statistically significant. The Na+, K+ ATPase activity and cAMP content were significantly higher in the iloprost group than in the untreated group. These findings suggest the possibility that the cAMP-dependent protein kinase (A-kinase) system has an important influence on improvement in Na+, K+ ATPase activity.", "contents": "Effect of a prostaglandin I2 derivative (iloprost) on peripheral neuropathy of diabetic rats. PGE1 has been found to improve the symptoms of diabetic neuropathy. We considered that a PGI2 derivative may also have a similar action and therefore studied its effect in diabetic rats. Iloprost was administered intraperitoneally to streptozotocin-induced diabetic rats at a dose of 10 micrograms/kg/day for a month. The changes in nerve conduction velocity (NCV) were measured in the tail. One day after the last dose of iloprost, both sciatic nerves were removed from each rat, homogenized, and extracted with 6% TCA. The sorbitol and myo-inositol concentrations were determined by a combination of HPLC and an enzymatic method. Cyclic AMP (cAMP) levels were determined by RIA, and Na+, K+ ATPase activity was assessed by the enzyme cycling method of Greene and Lattimer. Iloprost was found to improve the NCV in the diabetic rats. The sorbitol content was not affected by iloprost, but the myo-inositol content was higher in the iloprost group than in the untreated group, although the difference was not statistically significant. The Na+, K+ ATPase activity and cAMP content were significantly higher in the iloprost group than in the untreated group. These findings suggest the possibility that the cAMP-dependent protein kinase (A-kinase) system has an important influence on improvement in Na+, K+ ATPase activity."} {"id": "PMID:1282453", "title": "Human motor evoked responses to paired transcranial magnetic stimuli.", "content": "We studied the changes in motor pathway excitability induced by transcranial magnetic stimulation of the motor cortex, using paired stimuli (conditioning and test stimulus) and varying interstimulus interval (ISI). The effects induced depended on the stimulus intensity. At a low intensity, there was inhibition of the response to the test stimulus at ISIs of 5-40 msec, followed by facilitation at ISIs of 50-90 msec. At a high intensity, there was facilitation at ISIs of 25-50 msec, followed by inhibition at ISIs of 60-150 msec and, occasionally, by another phase of facilitation at ISIs of more than 200 msec. Only tentative explanations are currently possible for these effects: the inhibition observed at low intensities and short ISIs may be due to activation of cortical inhibitory mechanisms. The facilitation that follows may arise from the coincidence of various factors that transiently increase the excitability in alpha motoneurons. The early facilitation observed at high intensities seems to be a consequence of a rise in cortical excitability induced by the conditioning stimulus, causing an increase in the number or size, or both, of descending volleys from the test stimulus. The profound inhibition that follows probably results from a combination of both segmental and suprasegmental inhibitory mechanisms.", "contents": "Human motor evoked responses to paired transcranial magnetic stimuli. We studied the changes in motor pathway excitability induced by transcranial magnetic stimulation of the motor cortex, using paired stimuli (conditioning and test stimulus) and varying interstimulus interval (ISI). The effects induced depended on the stimulus intensity. At a low intensity, there was inhibition of the response to the test stimulus at ISIs of 5-40 msec, followed by facilitation at ISIs of 50-90 msec. At a high intensity, there was facilitation at ISIs of 25-50 msec, followed by inhibition at ISIs of 60-150 msec and, occasionally, by another phase of facilitation at ISIs of more than 200 msec. Only tentative explanations are currently possible for these effects: the inhibition observed at low intensities and short ISIs may be due to activation of cortical inhibitory mechanisms. The facilitation that follows may arise from the coincidence of various factors that transiently increase the excitability in alpha motoneurons. The early facilitation observed at high intensities seems to be a consequence of a rise in cortical excitability induced by the conditioning stimulus, causing an increase in the number or size, or both, of descending volleys from the test stimulus. The profound inhibition that follows probably results from a combination of both segmental and suprasegmental inhibitory mechanisms."} {"id": "PMID:1282454", "title": "Early and late lower limb motor evoked potentials elicited by transcranial magnetic motor cortex stimulation.", "content": "Transcranial magnetic motor cortex stimulation can elicit a series of responses recorded with different latencies from relaxed muscles of the lower limbs. In 7 healthy subjects, ranging in age from 16 to 62 years, stimulation was delivered by a 9 cm coil centered over Cz with the subject in the supine position. Surface polyelectromyography was used to record motor evoked potentials (MEPs) from the quadriceps (QD), hamstrings (HS), tibialis anterior (TA) and triceps surae (TS) muscles bilaterally. Three characteristic responses were identified in each muscle group on the basis of amplitude and latency criteria, identified by latencies: the direct oligosynaptic response MEP30 appeared with a latency of 24.3 msec in the QD, 26.3 msec in the HS, 30.5 msec in the TA and 31.3 msec in the TS; MEP70 with latencies of 64 msec in the QD, 59 msec in the HS, 79 msec in the TA and 72 msec in the TS; MEP120 with latencies of 115 msec in the QD, 126 msec in the HS, 117 msec in the TA and 124 msec in the TS. These 3 responses have distinct latencies, amplitudes and durations. MEP70 appears to be the result of activation of long descending tracts which end on spinal interneuronal circuits. As MEP120 has different features, it may have a different mechanism.", "contents": "Early and late lower limb motor evoked potentials elicited by transcranial magnetic motor cortex stimulation. Transcranial magnetic motor cortex stimulation can elicit a series of responses recorded with different latencies from relaxed muscles of the lower limbs. In 7 healthy subjects, ranging in age from 16 to 62 years, stimulation was delivered by a 9 cm coil centered over Cz with the subject in the supine position. Surface polyelectromyography was used to record motor evoked potentials (MEPs) from the quadriceps (QD), hamstrings (HS), tibialis anterior (TA) and triceps surae (TS) muscles bilaterally. Three characteristic responses were identified in each muscle group on the basis of amplitude and latency criteria, identified by latencies: the direct oligosynaptic response MEP30 appeared with a latency of 24.3 msec in the QD, 26.3 msec in the HS, 30.5 msec in the TA and 31.3 msec in the TS; MEP70 with latencies of 64 msec in the QD, 59 msec in the HS, 79 msec in the TA and 72 msec in the TS; MEP120 with latencies of 115 msec in the QD, 126 msec in the HS, 117 msec in the TA and 124 msec in the TS. These 3 responses have distinct latencies, amplitudes and durations. MEP70 appears to be the result of activation of long descending tracts which end on spinal interneuronal circuits. As MEP120 has different features, it may have a different mechanism."} {"id": "PMID:1282455", "title": "Transcranial cortical stimulation. Late excitability changes in the soleus and anterior tibial motoneurone pools.", "content": "The effect of conditioning magnetic transcranial cortical stimulation (TCCS) on the excitability levels of the soleus and anterior tibial motoneurone pools was studied by Hmax/2 technique 40-400 msec after the stimulus. The target muscles were relaxed throughout the tests. Two periods of facilitation (the first at 80-100 msec and the second at 180-200 msec) were found. They shared approximately the same latencies as the late responses (S100 and S > 150) that we have previously recorded following TCCS. A period of inhibition that started at 150 msec was also recorded. A period of facilitation could also be noted when the conditioning stimulus was applied either over the deltoid muscle or when the click that accompanied the magnetic pulse was used. This suggests that brain-stem areas related to those of the startle reaction play an important role for the appearance of the facilitatory changes. The necessary input probably comes from both peripheral and cortical sources.", "contents": "Transcranial cortical stimulation. Late excitability changes in the soleus and anterior tibial motoneurone pools. The effect of conditioning magnetic transcranial cortical stimulation (TCCS) on the excitability levels of the soleus and anterior tibial motoneurone pools was studied by Hmax/2 technique 40-400 msec after the stimulus. The target muscles were relaxed throughout the tests. Two periods of facilitation (the first at 80-100 msec and the second at 180-200 msec) were found. They shared approximately the same latencies as the late responses (S100 and S > 150) that we have previously recorded following TCCS. A period of inhibition that started at 150 msec was also recorded. A period of facilitation could also be noted when the conditioning stimulus was applied either over the deltoid muscle or when the click that accompanied the magnetic pulse was used. This suggests that brain-stem areas related to those of the startle reaction play an important role for the appearance of the facilitatory changes. The necessary input probably comes from both peripheral and cortical sources."} {"id": "PMID:1282456", "title": "Cortical projection to erector spinae muscles in man as assessed by focal transcranial magnetic stimulation.", "content": "We stimulated the motor cortex in 9 subjects using focal transcranial magnetic stimulation with a figure of 8 coil in order to examine the cortical representation of the erector spinae muscles. Recordings were made from the erector spinae 3.5 cm lateral to the third lumbar vertebra. In 5 subjects clearly reproducible responses could be obtained which had a latency compatible with transmission via fast conducting fibers in a mono- or oligosynaptic pathway. In the remaining 4 subjects responses were poorly defined. Latencies in surface recordings varied between 13 and 24 msec but were longer when needle recordings were used. Mapping of the motor cortex was performed by moving the coil in 2 cm steps on either side of Cz. Different patterns of hemispheric representation were found ranging from a contralateral projection in either hemisphere to a representation of both back muscles in one hemisphere (2 subjects). Responses were followed by a silent period. The latter was interrupted or terminated by a response between 52 and 85 msec post stimulus which was found predominantly in the muscle ipsilateral to the side of stimulation.", "contents": "Cortical projection to erector spinae muscles in man as assessed by focal transcranial magnetic stimulation. We stimulated the motor cortex in 9 subjects using focal transcranial magnetic stimulation with a figure of 8 coil in order to examine the cortical representation of the erector spinae muscles. Recordings were made from the erector spinae 3.5 cm lateral to the third lumbar vertebra. In 5 subjects clearly reproducible responses could be obtained which had a latency compatible with transmission via fast conducting fibers in a mono- or oligosynaptic pathway. In the remaining 4 subjects responses were poorly defined. Latencies in surface recordings varied between 13 and 24 msec but were longer when needle recordings were used. Mapping of the motor cortex was performed by moving the coil in 2 cm steps on either side of Cz. Different patterns of hemispheric representation were found ranging from a contralateral projection in either hemisphere to a representation of both back muscles in one hemisphere (2 subjects). Responses were followed by a silent period. The latter was interrupted or terminated by a response between 52 and 85 msec post stimulus which was found predominantly in the muscle ipsilateral to the side of stimulation."} {"id": "PMID:1282457", "title": "Assessment of corticospinal and somatosensory conduction simultaneously during scoliosis surgery.", "content": "The function of descending motor pathways and that of ascending sensory pathways in the spinal cord were monitored at the same time in 120 patients undergoing surgery for scoliosis. Transcranial electrical stimulation of the motor cortex was performed simultaneously with stimulation of the tibial nerves in the popliteal fossae, and the descending and ascending volleys were recorded from the spinal cord at two levels using epidural electrodes. Stable recordings of both volleys have been obtained in all neurologically normal patients and in many with pre-existing neurological deficits. The experimental conditions which resulted in reliable recordings were explored in select patients and include: a vertex-anode/lateral cathode montage for transcranial stimulation, epidural recording of evoked corticospinal and somatosensory volleys at two spinal levels, a high-pass filter of 500 Hz, and stable anaesthesia. The epidural recording allows full muscle relaxation and the use of volatile anaesthetics; recording at two levels allows a deterioration in function to be identified quickly and distinguished from an artifactual change.", "contents": "Assessment of corticospinal and somatosensory conduction simultaneously during scoliosis surgery. The function of descending motor pathways and that of ascending sensory pathways in the spinal cord were monitored at the same time in 120 patients undergoing surgery for scoliosis. Transcranial electrical stimulation of the motor cortex was performed simultaneously with stimulation of the tibial nerves in the popliteal fossae, and the descending and ascending volleys were recorded from the spinal cord at two levels using epidural electrodes. Stable recordings of both volleys have been obtained in all neurologically normal patients and in many with pre-existing neurological deficits. The experimental conditions which resulted in reliable recordings were explored in select patients and include: a vertex-anode/lateral cathode montage for transcranial stimulation, epidural recording of evoked corticospinal and somatosensory volleys at two spinal levels, a high-pass filter of 500 Hz, and stable anaesthesia. The epidural recording allows full muscle relaxation and the use of volatile anaesthetics; recording at two levels allows a deterioration in function to be identified quickly and distinguished from an artifactual change."} {"id": "PMID:1282458", "title": "Suppression of cutaneous perception by magnetic pulse stimulation of the human brain.", "content": "We have demonstrated that magnetic pulse stimulation of the sensorimotor cortex suppresses perception of threshold electrical stimuli to the fingers of the contralateral hand. Maximum suppression of perception occurs when the fingers are stimulated 30-90 msec after the magnetic pulse. Thereafter, errors in perception of the cutaneous stimulus decrease to control levels by 300-400 msec after the magnetic pulse. The period of maximum suppression of perception coincides with the period during which cortically generated somatosensory evoked potentials (SEPs) are enhanced following magnetic pulse stimulation of the brain. The duration of suppression of perception, however, outlasts the duration of SEP enhancement. When the magnetic pulse is delivered after finger stimulation there is also suppression of perception. The suppression of perception is maximal when the magnetic pulse occurs 20-30 msec after finger stimulation. This interval coincides with the arrival of the afferent volley at the primary sensory cortex.", "contents": "Suppression of cutaneous perception by magnetic pulse stimulation of the human brain. We have demonstrated that magnetic pulse stimulation of the sensorimotor cortex suppresses perception of threshold electrical stimuli to the fingers of the contralateral hand. Maximum suppression of perception occurs when the fingers are stimulated 30-90 msec after the magnetic pulse. Thereafter, errors in perception of the cutaneous stimulus decrease to control levels by 300-400 msec after the magnetic pulse. The period of maximum suppression of perception coincides with the period during which cortically generated somatosensory evoked potentials (SEPs) are enhanced following magnetic pulse stimulation of the brain. The duration of suppression of perception, however, outlasts the duration of SEP enhancement. When the magnetic pulse is delivered after finger stimulation there is also suppression of perception. The suppression of perception is maximal when the magnetic pulse occurs 20-30 msec after finger stimulation. This interval coincides with the arrival of the afferent volley at the primary sensory cortex."} {"id": "PMID:1282459", "title": "Simultaneous electromyography and 31P nuclear magnetic resonance spectroscopy--with application to muscle fatigue.", "content": "The electromyogram (EMG) is often used to study human muscle fatigue, but the changes in the electromyographic signals during muscle contraction are not well understood in relation to muscle metabolism. The 31P NMR spectroscopy is a semi-quantitative non-invasive method for studying the metabolic changes in human muscle. The aim of this study was to develop a method by which EMG and NMR spectroscopy measurements could be performed simultaneously. All measurements were performed in a whole body 1.5 Tesla NMR scanner. A calf muscle ergometer, designed for use in a whole body NMR scanner, was used. The subject had the left foot strapped to the ergometer. The anterior tibial EMG was recorded by bipolar surface electrodes. A surface coil was strapped to the anterior tibial muscle next to the EMG electrodes. Simultaneous measurements of surface EMG and surface coil 31P NMR spectroscopy were performed in the scanner during an isometric submaximal voluntary contraction until exhaustion, in 6 normal volunteers. Concentrations of phosphocreatine (PCr), inorganic phosphate (P(i)) and pH were analysed together with root mean square (RMS) and median frequency of the EMG. The fatiguing contractions (endured 5-13 min) produced a rapid decline in PCr and pH accompanied by a rapid rise in P(i). The RMS was approximately constant until the normalized PCr concentration declined below 0.6-0.7 and the pH declined below 6.75-6.85; exceeding these metabolic limits was associated with a rapidly increasing RMS value (2-3 times the previous level by exhaustion). The median frequency declined linearly with time and was found to be highly linearly correlated with the pH value (r = 0.82).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Simultaneous electromyography and 31P nuclear magnetic resonance spectroscopy--with application to muscle fatigue. The electromyogram (EMG) is often used to study human muscle fatigue, but the changes in the electromyographic signals during muscle contraction are not well understood in relation to muscle metabolism. The 31P NMR spectroscopy is a semi-quantitative non-invasive method for studying the metabolic changes in human muscle. The aim of this study was to develop a method by which EMG and NMR spectroscopy measurements could be performed simultaneously. All measurements were performed in a whole body 1.5 Tesla NMR scanner. A calf muscle ergometer, designed for use in a whole body NMR scanner, was used. The subject had the left foot strapped to the ergometer. The anterior tibial EMG was recorded by bipolar surface electrodes. A surface coil was strapped to the anterior tibial muscle next to the EMG electrodes. Simultaneous measurements of surface EMG and surface coil 31P NMR spectroscopy were performed in the scanner during an isometric submaximal voluntary contraction until exhaustion, in 6 normal volunteers. Concentrations of phosphocreatine (PCr), inorganic phosphate (P(i)) and pH were analysed together with root mean square (RMS) and median frequency of the EMG. The fatiguing contractions (endured 5-13 min) produced a rapid decline in PCr and pH accompanied by a rapid rise in P(i). The RMS was approximately constant until the normalized PCr concentration declined below 0.6-0.7 and the pH declined below 6.75-6.85; exceeding these metabolic limits was associated with a rapidly increasing RMS value (2-3 times the previous level by exhaustion). The median frequency declined linearly with time and was found to be highly linearly correlated with the pH value (r = 0.82).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282460", "title": "Mechanical properties of human ankle extensors after muscle potentiation.", "content": "The contractile properties of a muscle depend on the activation history of its motor units. At the same time as fatigue seems to impair muscle excitation-contraction coupling, post-tetanic potentiation can augment force production. The effects of post-tetanic potentiation on the mechanical muscle properties of the intact human ankle extensor muscles were investigated by a 4 degree dorsiflexion of the ankle joint during a sustained contraction. The contraction was elicited by 10 Hz electrical stimulation of the tibial nerve. The changes in the contraction torque and in the intrinsic muscle stiffness of the ankle extensors before and after prolonged electrically elicited muscle activation were measured. From the onset of continuous synchronized 10 Hz stimulation to the attainment of maximal torque, the ankle joint torque increased by 47%. At matched background contraction, the prolonged electrically elicited contraction increased the intrinsic muscle stiffness by 49%. The first stretch after prolonged stimulation gave rise to a 17% yield in the background contraction and a 73% yield in the torque increment. The findings imply that with fatigue an increase in the intrinsic stiffness of the pre-stretched muscle might operate as a \"safety factor\" to compensate for a reduced reflex-induced stiffness, keeping the total muscle resistance at a high level in the active muscle.", "contents": "Mechanical properties of human ankle extensors after muscle potentiation. The contractile properties of a muscle depend on the activation history of its motor units. At the same time as fatigue seems to impair muscle excitation-contraction coupling, post-tetanic potentiation can augment force production. The effects of post-tetanic potentiation on the mechanical muscle properties of the intact human ankle extensor muscles were investigated by a 4 degree dorsiflexion of the ankle joint during a sustained contraction. The contraction was elicited by 10 Hz electrical stimulation of the tibial nerve. The changes in the contraction torque and in the intrinsic muscle stiffness of the ankle extensors before and after prolonged electrically elicited muscle activation were measured. From the onset of continuous synchronized 10 Hz stimulation to the attainment of maximal torque, the ankle joint torque increased by 47%. At matched background contraction, the prolonged electrically elicited contraction increased the intrinsic muscle stiffness by 49%. The first stretch after prolonged stimulation gave rise to a 17% yield in the background contraction and a 73% yield in the torque increment. The findings imply that with fatigue an increase in the intrinsic stiffness of the pre-stretched muscle might operate as a \"safety factor\" to compensate for a reduced reflex-induced stiffness, keeping the total muscle resistance at a high level in the active muscle."} {"id": "PMID:1282461", "title": "Supraspinal influences on recurrent inhibition in humans. Paralysis of descending control of Renshaw cells in patients with mental retardation.", "content": "The recurrent inhibition of alpha motoneurons was studied in 8 mentally retarded subjects (age 16-35 years), six of whom also had non-pyramidal or extrapyramidal motor alterations, manifesting as rigid and inflexible voluntary and/or postural movements. Despite a similar degree of mental retardation (Raven spatial general intelligence test), the other 2 cases showed much more modest changes in motor behavior. At rest, recurrent inhibition on soleus motoneurons was normal in all patients. In the 6 cases exhibiting more severe motor abnormality, the changes in Renshaw cell excitability, which occur during postural or voluntary contractions in normal subjects, were not found. This expressed the lack of supraspinal influences on Renshaw cells in these patients. On the other hand, supraspinal modulating influences on Renshaw cells were virtually normal in the remaining 2 patients. The absence of excitability changes of recurrent inhibition to postural or voluntary movements is discussed in relation to the abnormality of motor behavior observed in these patients. In addition, since paralysis of adaptive changes of recurrent inhibition has so far only been described in spastic subjects, the present study demonstrates that the descending pathways, which control recurrent inhibition gain, are different from those which, when damaged, lead to spasticity. Finally, our results indicate that the changes in motor behavior often associated with mental retardation cannot be regarded merely as the consequence of defective motor learning.", "contents": "Supraspinal influences on recurrent inhibition in humans. Paralysis of descending control of Renshaw cells in patients with mental retardation. The recurrent inhibition of alpha motoneurons was studied in 8 mentally retarded subjects (age 16-35 years), six of whom also had non-pyramidal or extrapyramidal motor alterations, manifesting as rigid and inflexible voluntary and/or postural movements. Despite a similar degree of mental retardation (Raven spatial general intelligence test), the other 2 cases showed much more modest changes in motor behavior. At rest, recurrent inhibition on soleus motoneurons was normal in all patients. In the 6 cases exhibiting more severe motor abnormality, the changes in Renshaw cell excitability, which occur during postural or voluntary contractions in normal subjects, were not found. This expressed the lack of supraspinal influences on Renshaw cells in these patients. On the other hand, supraspinal modulating influences on Renshaw cells were virtually normal in the remaining 2 patients. The absence of excitability changes of recurrent inhibition to postural or voluntary movements is discussed in relation to the abnormality of motor behavior observed in these patients. In addition, since paralysis of adaptive changes of recurrent inhibition has so far only been described in spastic subjects, the present study demonstrates that the descending pathways, which control recurrent inhibition gain, are different from those which, when damaged, lead to spasticity. Finally, our results indicate that the changes in motor behavior often associated with mental retardation cannot be regarded merely as the consequence of defective motor learning."} {"id": "PMID:1282462", "title": "Central motor conduction in relation to contra- and ipsilateral activation.", "content": "Differences of central motor conduction between slight activation of the target muscle (ipsilateral: IL) and strong contraction of the contralateral (CL) muscle following magnetic motor cortex stimulation were studied in 18 controls; responses were recorded at abductor pollicis brevis (APB) and tibial anterior (TA). For APB a clearly faster response was obtained with IL activation (mean: 1.7 msec). The amplitude increased only slightly. The reverse was found for TA muscle: amplitude nearly doubled with IL activation, but the latency did not change. In both facilitation procedures a clear correlation was found between left and right normalised amplitude (cortex amplitude/M wave) for APB and TA, but not for the TA response with IL activation. This points to a different mechanism of enhancement for the ipsilateral activation of TA muscle. It is argued that a rise in excitability of spinal motoneurones is largely responsible for the increase in amplitude. In clinical practice contralateral activation as a method of facilitation seems appropriate in most cases: lack of EMG contamination of the baseline makes it easier to read the latency onset. Only in cases of a low TA response can IL activation give a better response.", "contents": "Central motor conduction in relation to contra- and ipsilateral activation. Differences of central motor conduction between slight activation of the target muscle (ipsilateral: IL) and strong contraction of the contralateral (CL) muscle following magnetic motor cortex stimulation were studied in 18 controls; responses were recorded at abductor pollicis brevis (APB) and tibial anterior (TA). For APB a clearly faster response was obtained with IL activation (mean: 1.7 msec). The amplitude increased only slightly. The reverse was found for TA muscle: amplitude nearly doubled with IL activation, but the latency did not change. In both facilitation procedures a clear correlation was found between left and right normalised amplitude (cortex amplitude/M wave) for APB and TA, but not for the TA response with IL activation. This points to a different mechanism of enhancement for the ipsilateral activation of TA muscle. It is argued that a rise in excitability of spinal motoneurones is largely responsible for the increase in amplitude. In clinical practice contralateral activation as a method of facilitation seems appropriate in most cases: lack of EMG contamination of the baseline makes it easier to read the latency onset. Only in cases of a low TA response can IL activation give a better response."} {"id": "PMID:1282463", "title": "Gonadotropin induces expression of c-fos and c-jun genes in rat ovaries.", "content": "It has been shown that the expression of protooncogenes, c-fos and c-jun, induced by growth factors and hormones plays important roles in cellular proliferation, tissue differentiation and transcription of certain genes. Since gonadotropin stimulates ovarian steroidogenesis and cellular proliferation, we investigated whether gonadotropin affects the expression of c-fos and c-jun genes in rat ovaries. The expression of mRNA coding side chain cleavage enzyme (P450scc), the rate limiting enzyme in ovarian steroidogenesis was also studied. The effect of gonadotropin was examined in female rats whose gonadotrophs were medically ablated by GnRH agonist (TAP-144-SR). After intravenous administration of pregnant mare's serum gonadotropin (PMSG:30 IU/rat), their ovaries were dissected out at various time intervals and total RNA was extracted. Changes in the levels of c-fos, c-jun and P450scc mRNAs were determined by Northern blot analysis. The levels of c-fos and c-jun mRNAs increased rapidly and transiently with the peak levels at 15 min after PMSG administration. The levels of both mRNAs were decreased by 30 to 60 min. On the other hand, the levels of P450scc mRNA started to increase 60 min after PMSG. These results indicate that gonadotropin-induced increase in the expression of c-fos and c-jun genes may play important roles in mediating the action of gonadotropin on the ovaries.", "contents": "Gonadotropin induces expression of c-fos and c-jun genes in rat ovaries. It has been shown that the expression of protooncogenes, c-fos and c-jun, induced by growth factors and hormones plays important roles in cellular proliferation, tissue differentiation and transcription of certain genes. Since gonadotropin stimulates ovarian steroidogenesis and cellular proliferation, we investigated whether gonadotropin affects the expression of c-fos and c-jun genes in rat ovaries. The expression of mRNA coding side chain cleavage enzyme (P450scc), the rate limiting enzyme in ovarian steroidogenesis was also studied. The effect of gonadotropin was examined in female rats whose gonadotrophs were medically ablated by GnRH agonist (TAP-144-SR). After intravenous administration of pregnant mare's serum gonadotropin (PMSG:30 IU/rat), their ovaries were dissected out at various time intervals and total RNA was extracted. Changes in the levels of c-fos, c-jun and P450scc mRNAs were determined by Northern blot analysis. The levels of c-fos and c-jun mRNAs increased rapidly and transiently with the peak levels at 15 min after PMSG administration. The levels of both mRNAs were decreased by 30 to 60 min. On the other hand, the levels of P450scc mRNA started to increase 60 min after PMSG. These results indicate that gonadotropin-induced increase in the expression of c-fos and c-jun genes may play important roles in mediating the action of gonadotropin on the ovaries."} {"id": "PMID:1282465", "title": "Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man.", "content": "To explore the interactions between cholecystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose-dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg-1 h-1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 micrograms kg-1 h-1), however, only reduced gallbladder contraction and enzyme output to CCK8. Gallbladder volumes decreased maximally to 12 +/- 4% after oral food, whereas enzyme output and plasma CCK levels increased 6- to 8-fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion. The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response.", "contents": "Postprandial control of gallbladder contraction and exocrine pancreatic secretion in man. To explore the interactions between cholecystokinin (CCK) and the cholinergic system, we compared the effect of cholinergic or peptidergic CCK blockade on gallbladder contraction and pancreatic enzyme secretion using atropine and loxiglumide (a specific CCK antagonist) as pharmacological tools. Gallbladder contraction was measured by sonography and pancreatic secretion by a marker perfusion and aspiration technique. Graded doses of exogenous CCK8 induced dose-dependent contractions of the gallbladder and increasing enzyme outputs. Loxiglumide (10 mg kg-1 h-1) abolished the gallbladder response and prevented an increase in pancreatic enzyme secretion to CCK8. Atropine (5 micrograms kg-1 h-1), however, only reduced gallbladder contraction and enzyme output to CCK8. Gallbladder volumes decreased maximally to 12 +/- 4% after oral food, whereas enzyme output and plasma CCK levels increased 6- to 8-fold. Loxiglumide completely abolished gallbladder contraction and inhibited enzyme secretion by 30%. Atropine caused a small reduction in gallbladder volumes, but essentially blocked postprandial enzyme secretion. The results indicate that CCK is the major regulator of gallbladder contraction with the cholinergic system modulating the response, while the exocrine pancreas is crucially dependent on a cholinergic background with CCK modulating the secretory response."} {"id": "PMID:1282466", "title": "The long-term inhibitory effect of a Ca2+ channel blocker, nisoldipine, on cytosolic Ca2+ and contraction in vascular smooth muscle.", "content": "The mechanism of the long-term inhibitory effect of a dihydropyridine Ca2+ channel blocker, nisoldipine, on contraction and cytosolic Ca2+ level ([Ca2+]i) was examined in isolated rat aorta. Nisoldipine inhibited the [Ca2+]i and muscle tension induced by high K+. The inhibitory effects were antagonized by a Ca2+ channel activator, 100 nM Bay k8644, and by a high concentration of Ca2+ (6.5 mM). Ultraviolet light, which has been shown to decompose dihydropyridines, attenuated the effects of nisoldipine. After nisoldipine had been removed from muscle bath, the inhibitory effect faded away slowly. The residual inhibitory effects on [Ca2+]i and muscle tension were antagonized by Bay k8644, high Ca2+ and ultraviolet light. These results suggest that the inhibitory effect of nisoldipine is caused by a decrease in [Ca2+]i as a result of inhibition of L-type Ca2+ channels, and that the residual inhibitory effects are caused by the same mechanism as the inhibitory effects of nisoldipine, namely the tight binding of nisoldipine to Ca2+ channels even after washout.", "contents": "The long-term inhibitory effect of a Ca2+ channel blocker, nisoldipine, on cytosolic Ca2+ and contraction in vascular smooth muscle. The mechanism of the long-term inhibitory effect of a dihydropyridine Ca2+ channel blocker, nisoldipine, on contraction and cytosolic Ca2+ level ([Ca2+]i) was examined in isolated rat aorta. Nisoldipine inhibited the [Ca2+]i and muscle tension induced by high K+. The inhibitory effects were antagonized by a Ca2+ channel activator, 100 nM Bay k8644, and by a high concentration of Ca2+ (6.5 mM). Ultraviolet light, which has been shown to decompose dihydropyridines, attenuated the effects of nisoldipine. After nisoldipine had been removed from muscle bath, the inhibitory effect faded away slowly. The residual inhibitory effects on [Ca2+]i and muscle tension were antagonized by Bay k8644, high Ca2+ and ultraviolet light. These results suggest that the inhibitory effect of nisoldipine is caused by a decrease in [Ca2+]i as a result of inhibition of L-type Ca2+ channels, and that the residual inhibitory effects are caused by the same mechanism as the inhibitory effects of nisoldipine, namely the tight binding of nisoldipine to Ca2+ channels even after washout."} {"id": "PMID:1282467", "title": "Effects of philanthotoxin-343 on CA1 pyramidal neurons of rat hippocampus in vitro.", "content": "A synthetic analog of philanthotoxin-433, philanthotoxin-343 (PhTX-343), was tested in hippocampal pyramidal neurons in vitro. PhTX-343 (2 microM) did not significantly change synaptic transmission mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptors in the CA1 region of hippocampus. However, PhTX-343 significantly suppressed both the synaptic N-methyl-D-aspartate receptor-induced current (NMDA) obtained in the presence of CNQX(6-cyano-7-nitroquinoxaline-2,3-dione)/picrotoxin (10 microM) and the directly evoked NMDA receptor-induced current to pressure ejection of NMDA in the presence of tetrodotoxin (0.5 microM). A short transient facilitation of both types of NMDA response was seen immediately after the beginning of PhTX-343 application. Our results suggest that at high concentration (2 microM) PhTX-343 inhibits the NMDA-gated current, while the early facilitation occurred during an initial low concentration of the compound. Both facilitative and depressive actions of PhTX-343 are localized at the postsynaptic membrane.", "contents": "Effects of philanthotoxin-343 on CA1 pyramidal neurons of rat hippocampus in vitro. A synthetic analog of philanthotoxin-433, philanthotoxin-343 (PhTX-343), was tested in hippocampal pyramidal neurons in vitro. PhTX-343 (2 microM) did not significantly change synaptic transmission mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/kainate receptors in the CA1 region of hippocampus. However, PhTX-343 significantly suppressed both the synaptic N-methyl-D-aspartate receptor-induced current (NMDA) obtained in the presence of CNQX(6-cyano-7-nitroquinoxaline-2,3-dione)/picrotoxin (10 microM) and the directly evoked NMDA receptor-induced current to pressure ejection of NMDA in the presence of tetrodotoxin (0.5 microM). A short transient facilitation of both types of NMDA response was seen immediately after the beginning of PhTX-343 application. Our results suggest that at high concentration (2 microM) PhTX-343 inhibits the NMDA-gated current, while the early facilitation occurred during an initial low concentration of the compound. Both facilitative and depressive actions of PhTX-343 are localized at the postsynaptic membrane."} {"id": "PMID:1282468", "title": "Lugol's iodine dye-enhanced endoscopy in patients with cancer of the oesophagus and head and neck.", "content": "Lugol's iodine dye indicates the presence of unsuspected early oesophageal cancers during endoscopy at which such cancers fail to show the characteristic black colour change. We evaluated Lugol's iodine dye-enhanced endoscopy in 17 patients with oesophageal cancer. In a further 37 patients with head and neck cancer we examined the use of Lugol's iodine since these patients have a 29% risk of synchronous oesophageal cancer. The oesophagus was sprayed with Lugol's iodine (1.5%) during endoscopy. Any areas not turning black were biopsied. In 13 patients with oesophageal cancer discrete areas beyond the macroscopically obvious primary tumour showed no change in colour. Biopsy revealed cancer in all cases. Six synchronous cancers were found in the head and neck group, one of which was identified only by the use of Lugol's iodine. Lugol's iodine augmented the information gained about the oesophageal mucosa during endoscopy. It revealed unsuspected cancer which altered the management of patients with primary oesophageal cancer as well as those with head and neck cancer. We recommend the routine use of Lugol's iodine-enhanced endoscopy for surveillance of all 'at risk' oesophageal cases.", "contents": "Lugol's iodine dye-enhanced endoscopy in patients with cancer of the oesophagus and head and neck. Lugol's iodine dye indicates the presence of unsuspected early oesophageal cancers during endoscopy at which such cancers fail to show the characteristic black colour change. We evaluated Lugol's iodine dye-enhanced endoscopy in 17 patients with oesophageal cancer. In a further 37 patients with head and neck cancer we examined the use of Lugol's iodine since these patients have a 29% risk of synchronous oesophageal cancer. The oesophagus was sprayed with Lugol's iodine (1.5%) during endoscopy. Any areas not turning black were biopsied. In 13 patients with oesophageal cancer discrete areas beyond the macroscopically obvious primary tumour showed no change in colour. Biopsy revealed cancer in all cases. Six synchronous cancers were found in the head and neck group, one of which was identified only by the use of Lugol's iodine. Lugol's iodine augmented the information gained about the oesophageal mucosa during endoscopy. It revealed unsuspected cancer which altered the management of patients with primary oesophageal cancer as well as those with head and neck cancer. We recommend the routine use of Lugol's iodine-enhanced endoscopy for surveillance of all 'at risk' oesophageal cases."} {"id": "PMID:1282469", "title": "[The structural-functional architectonics of the enteral portion of the metasympathetic nervous system in representative lower vertebrates--the teleosts].", "content": "The character of neurons and interrelations among them in submucous plexus were found to change along the digestive tract in lower vertebrates. The plexus looks like a network of ganglion-like structures composed of different number of cells. Specific feature of the plexus involves the absence of a regular ganglionic structure which seems to characterise a transitory stage in formation of the submucous plexus in vertebrates.", "contents": "[The structural-functional architectonics of the enteral portion of the metasympathetic nervous system in representative lower vertebrates--the teleosts]. The character of neurons and interrelations among them in submucous plexus were found to change along the digestive tract in lower vertebrates. The plexus looks like a network of ganglion-like structures composed of different number of cells. Specific feature of the plexus involves the absence of a regular ganglionic structure which seems to characterise a transitory stage in formation of the submucous plexus in vertebrates."} {"id": "PMID:1282470", "title": "[The formation of a hypokinetic syndrome of the digestive system under conditions of weightlessness].", "content": "In space flights of various duration, the gastropancreatic complex turned out to be the most liable part of the digestive system. The main changes occurring in the gastrointestinal tract involve an increase in the peptic gastric potential, pancreatic hyperenzymemia, change of the glycemic curve forms, a decrease in the liver and pancreas density.", "contents": "[The formation of a hypokinetic syndrome of the digestive system under conditions of weightlessness]. In space flights of various duration, the gastropancreatic complex turned out to be the most liable part of the digestive system. The main changes occurring in the gastrointestinal tract involve an increase in the peptic gastric potential, pancreatic hyperenzymemia, change of the glycemic curve forms, a decrease in the liver and pancreas density."} {"id": "PMID:1282471", "title": "Refsum disease: the presentation and ophthalmic aspects of Refsum disease in a series of 23 patients.", "content": "Refsum disease (heredopathia atactica polyneuritiformis) was first described in 1946 and is a rare recessively inherited metabolic disease affecting phytanic acid metabolism. It causes retinitis pigmentosa, cataracts, a chronic polyneuropathy, cerebellar ataxia and cardiac arrhythmias amongst other clinical signs. By limiting dietary intake, plasma phytanic acid levels fall with an improvement in the neurological signs. The onset of retinitis pigmentosa usually precedes biochemical diagnosis by several years by which time the retinal damage is severe. A series of 23 patients have been reviewed. There was an average delay of 11 years (range 1-28 years) between the patient presenting to the ophthalmologist and being diagnosed as having Refsum disease. Although serial examinations have failed to show a definite change in the course of visual deterioration with treatment, early diagnosis is important to prevent the development of neurological disease.", "contents": "Refsum disease: the presentation and ophthalmic aspects of Refsum disease in a series of 23 patients. Refsum disease (heredopathia atactica polyneuritiformis) was first described in 1946 and is a rare recessively inherited metabolic disease affecting phytanic acid metabolism. It causes retinitis pigmentosa, cataracts, a chronic polyneuropathy, cerebellar ataxia and cardiac arrhythmias amongst other clinical signs. By limiting dietary intake, plasma phytanic acid levels fall with an improvement in the neurological signs. The onset of retinitis pigmentosa usually precedes biochemical diagnosis by several years by which time the retinal damage is severe. A series of 23 patients have been reviewed. There was an average delay of 11 years (range 1-28 years) between the patient presenting to the ophthalmologist and being diagnosed as having Refsum disease. Although serial examinations have failed to show a definite change in the course of visual deterioration with treatment, early diagnosis is important to prevent the development of neurological disease."} {"id": "PMID:1282472", "title": "Expression of chimeric proteins encoded by the fused BLV reverse transcriptase: beta-galactosidase in Escherichia coli.", "content": "The gene for bovine leukemia virus (BLV) reverse transcriptase was cloned in prokaryotic expression vector pUC8-2. After fusion of Escherichia coli lacZ gene to different parts of reverse transcriptase we detected expression of new proteins with molecular weights corresponding to the size of the hybrid genes. A coding region most probably responsible for about a hundred-fold decrease in expression of long fusion proteins has been identified. A few possible causes of this phenomenon were tested.", "contents": "Expression of chimeric proteins encoded by the fused BLV reverse transcriptase: beta-galactosidase in Escherichia coli. The gene for bovine leukemia virus (BLV) reverse transcriptase was cloned in prokaryotic expression vector pUC8-2. After fusion of Escherichia coli lacZ gene to different parts of reverse transcriptase we detected expression of new proteins with molecular weights corresponding to the size of the hybrid genes. A coding region most probably responsible for about a hundred-fold decrease in expression of long fusion proteins has been identified. A few possible causes of this phenomenon were tested."} {"id": "PMID:1282474", "title": "Distribution of nonmuscle actin during Xenopus laevis development.", "content": "Using antisera specific for the N-terminal peptides of nonmuscle isoforms of actin we studied these proteins in the developing egg and embryo of Xenopus laevis. The antisera did not crossreact with muscle actin and did not react with the other nonmuscle isoform. By immunofluorescence we found a large maternal actin store in the oocyte, in the Balbiani body and the nucleoli, respectively. In the blastula, nonmuscle actin was preferentially expressed in the mitotic apparatus of the individual blastomeres. A gradual decrease in the amount of these isoforms in muscle tissue could be observed during development, apparently corresponding to an increase in the concentration of muscle specific isoforms. No differences between the distribution of the two isoforms could be found. The results would seem to indicate that development of the embryo is accompanied by a decline in the concentration of cytoskeletal actin isoforms down to an almost background level, accompanied by an increase in the concentration of the muscle specific isoforms. This points to potential function of nonmuscle actins in the early embryo.", "contents": "Distribution of nonmuscle actin during Xenopus laevis development. Using antisera specific for the N-terminal peptides of nonmuscle isoforms of actin we studied these proteins in the developing egg and embryo of Xenopus laevis. The antisera did not crossreact with muscle actin and did not react with the other nonmuscle isoform. By immunofluorescence we found a large maternal actin store in the oocyte, in the Balbiani body and the nucleoli, respectively. In the blastula, nonmuscle actin was preferentially expressed in the mitotic apparatus of the individual blastomeres. A gradual decrease in the amount of these isoforms in muscle tissue could be observed during development, apparently corresponding to an increase in the concentration of muscle specific isoforms. No differences between the distribution of the two isoforms could be found. The results would seem to indicate that development of the embryo is accompanied by a decline in the concentration of cytoskeletal actin isoforms down to an almost background level, accompanied by an increase in the concentration of the muscle specific isoforms. This points to potential function of nonmuscle actins in the early embryo."} {"id": "PMID:1282475", "title": "Industrial experience with the detection of retroviruses.", "content": "An important aspect of the virological assessment of cell substrates used to produce biologicals is their retroviral status. In this presentation we will attempt to document some of the practical experiences of industry when testing cell substrates for retroviruses using infectivity tests, reverse transcriptase and electron microscopy. We will also explore some important aspects of the experimental design of these retrovirus assay systems and review some results from the application of these methods in model, experimental systems.", "contents": "Industrial experience with the detection of retroviruses. An important aspect of the virological assessment of cell substrates used to produce biologicals is their retroviral status. In this presentation we will attempt to document some of the practical experiences of industry when testing cell substrates for retroviruses using infectivity tests, reverse transcriptase and electron microscopy. We will also explore some important aspects of the experimental design of these retrovirus assay systems and review some results from the application of these methods in model, experimental systems."} {"id": "PMID:1282476", "title": "Recent studies on retrovirus-like particles in Chinese hamster ovary cells.", "content": "Highly concentrated (4000-7000-fold) culture fluids from CHO cells were analysed for the presence of retrovirus-like activity. Concentrates containing reverse transcriptase activity were detected and further purified by sucrose density gradient centrifugation. Particles banding at 1.13-1.16 g/ml were found to contain nucleic acid sequences and structural proteins related to those found in murine and other retroviruses. Analysis of the endonuclease gene has shown no intact open reading frames. Approximately 100-300 copies of the C-type sequences were present in the genome of CHO cell lines as well as in the DNA extracted from Chinese hamster liver, indicating that these sequences are present in the germ line of the species. Concentrates were analysed for infectivity by direct inoculation and co-cultivation with a series of detector cells. No evidence of infectivity was detected by reverse transcriptase, mink cell S+L- focus assay or by electron microscopic analysis of the inoculated detector cells after at least four passages in culture.", "contents": "Recent studies on retrovirus-like particles in Chinese hamster ovary cells. Highly concentrated (4000-7000-fold) culture fluids from CHO cells were analysed for the presence of retrovirus-like activity. Concentrates containing reverse transcriptase activity were detected and further purified by sucrose density gradient centrifugation. Particles banding at 1.13-1.16 g/ml were found to contain nucleic acid sequences and structural proteins related to those found in murine and other retroviruses. Analysis of the endonuclease gene has shown no intact open reading frames. Approximately 100-300 copies of the C-type sequences were present in the genome of CHO cell lines as well as in the DNA extracted from Chinese hamster liver, indicating that these sequences are present in the germ line of the species. Concentrates were analysed for infectivity by direct inoculation and co-cultivation with a series of detector cells. No evidence of infectivity was detected by reverse transcriptase, mink cell S+L- focus assay or by electron microscopic analysis of the inoculated detector cells after at least four passages in culture."} {"id": "PMID:1282477", "title": "Differential expression of rat pancreatic islet beta-cell glucose transporter (GLUT 2), proinsulin and islet amyloid polypeptide genes after prolonged fasting, insulin-induced hypoglycaemia and dexamethasone treatment.", "content": "The question posed by these studies was whether chronic adaptive changes in glucose-stimulated insulin secretion are accompanied by comparable changes in islet Beta-cell glucose transporter (GLUT 2) gene expression. Control, fasted (3-day), insulin-injected hypoglycaemic (5-day), and dexamethasone-treated (4-day) rats (n = 5 for each condition), were studied. After fasting significant decrements in proinsulin mRNA/microgram RNA (-32%, p < 0.05) and islet amyloid polypeptide mRNA/microgram RNA (-44%, p < 0.05) were observed, while there was no change in GLUT 2 mRNA/microgram RNA (-13%, p > 0.05). After insulin-induced hypoglycaemia, decrements in proinsulin mRNA/microgram RNA (-49%, p < 0.01) and islet amyloid polypeptide mRNA/microgram RNA (-44%, p < 0.01) were also observed, with no change in islet GLUT 2 mRNA/microgram RNA (-18%, p > 0.05). Dexamethasone treatment resulted in a marked stimulatory effect on proinsulin mRNA/microgram RNA (+236%, p < 0.001) and islet amyloid polypeptide mRNA/microgram RNA (+221%, p < 0.01), while again there was no change in islet GLUT 2 mRNA/microgram RNA (+0.3%, p > 0.05). Quantitative immunoblot analysis with a GLUT 2 specific antibody revealed no change in islet GLUT 2 protein with fasting, but a small decrease (-39 +/- 11%) in islet GLUT 2/microgram protein after insulin-induced hypoglycaemia. These results do not support the hypothesis that chronic changes in glucose-stimulated insulin secretion are accompanied by changes in GLUT 2 expression. In contrast to the lack of correlation with GLUT 2, there was a striking correlation between proinsulin and islet amyloid polypeptide mRNAs for all experimental conditions (r = 0.974, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Differential expression of rat pancreatic islet beta-cell glucose transporter (GLUT 2), proinsulin and islet amyloid polypeptide genes after prolonged fasting, insulin-induced hypoglycaemia and dexamethasone treatment. The question posed by these studies was whether chronic adaptive changes in glucose-stimulated insulin secretion are accompanied by comparable changes in islet Beta-cell glucose transporter (GLUT 2) gene expression. Control, fasted (3-day), insulin-injected hypoglycaemic (5-day), and dexamethasone-treated (4-day) rats (n = 5 for each condition), were studied. After fasting significant decrements in proinsulin mRNA/microgram RNA (-32%, p < 0.05) and islet amyloid polypeptide mRNA/microgram RNA (-44%, p < 0.05) were observed, while there was no change in GLUT 2 mRNA/microgram RNA (-13%, p > 0.05). After insulin-induced hypoglycaemia, decrements in proinsulin mRNA/microgram RNA (-49%, p < 0.01) and islet amyloid polypeptide mRNA/microgram RNA (-44%, p < 0.01) were also observed, with no change in islet GLUT 2 mRNA/microgram RNA (-18%, p > 0.05). Dexamethasone treatment resulted in a marked stimulatory effect on proinsulin mRNA/microgram RNA (+236%, p < 0.001) and islet amyloid polypeptide mRNA/microgram RNA (+221%, p < 0.01), while again there was no change in islet GLUT 2 mRNA/microgram RNA (+0.3%, p > 0.05). Quantitative immunoblot analysis with a GLUT 2 specific antibody revealed no change in islet GLUT 2 protein with fasting, but a small decrease (-39 +/- 11%) in islet GLUT 2/microgram protein after insulin-induced hypoglycaemia. These results do not support the hypothesis that chronic changes in glucose-stimulated insulin secretion are accompanied by changes in GLUT 2 expression. In contrast to the lack of correlation with GLUT 2, there was a striking correlation between proinsulin and islet amyloid polypeptide mRNAs for all experimental conditions (r = 0.974, p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282478", "title": "Ion channels.", "content": "Insulin secretion by the pancreatic Beta cell is dependent upon transmembrane ion fluxes gated by the ATP-regulated potassium channel and the voltage regulated, L-type calcium channel. This work group examined major recent advances in the structure and modulation of ion channels and how those advances may pertain to the physiology of insulin secretion and the pharmacological treatment of Type 2 (non-insulin-dependent) diabetes mellitus. Structural studies have revealed that voltage gated ion channels are related, complex, and comprised of multiple components: sodium channels consist of three distinct subunits. L-type calcium channels, crucial to the insulin secretory response are structurally related to the sodium channel but contain additional subunits. Potassium channels are less closely related and appear to function as homotetramers. Modulation of ion channel activity is similarly complex: site specific phosphorylation by multiple protein kinases under the control of several intracellular second messenger systems may increase or decrease conductance. Subunit composition and relatively stable changes in the modal state of ion channels also appear to be critical to ion channel gating properties. Functional studies of the Beta-cell ATP-regulated potassium channel suggest two distinct nucleotide binding sites which link this channel to the metabolic state of the Beta cell. The multiple paths of ion channel modulation provide multiple targets for therapeutic intervention. Where detailed characterisation of ion channel structure has been achieved, those targets are being used for specific drug design. Such complete characterisation has not yet been achieved for Beta-cell ion channels and this presents a major goal for diabetes research.", "contents": "Ion channels. Insulin secretion by the pancreatic Beta cell is dependent upon transmembrane ion fluxes gated by the ATP-regulated potassium channel and the voltage regulated, L-type calcium channel. This work group examined major recent advances in the structure and modulation of ion channels and how those advances may pertain to the physiology of insulin secretion and the pharmacological treatment of Type 2 (non-insulin-dependent) diabetes mellitus. Structural studies have revealed that voltage gated ion channels are related, complex, and comprised of multiple components: sodium channels consist of three distinct subunits. L-type calcium channels, crucial to the insulin secretory response are structurally related to the sodium channel but contain additional subunits. Potassium channels are less closely related and appear to function as homotetramers. Modulation of ion channel activity is similarly complex: site specific phosphorylation by multiple protein kinases under the control of several intracellular second messenger systems may increase or decrease conductance. Subunit composition and relatively stable changes in the modal state of ion channels also appear to be critical to ion channel gating properties. Functional studies of the Beta-cell ATP-regulated potassium channel suggest two distinct nucleotide binding sites which link this channel to the metabolic state of the Beta cell. The multiple paths of ion channel modulation provide multiple targets for therapeutic intervention. Where detailed characterisation of ion channel structure has been achieved, those targets are being used for specific drug design. Such complete characterisation has not yet been achieved for Beta-cell ion channels and this presents a major goal for diabetes research."} {"id": "PMID:1282481", "title": "Effects of estradiol on brain aminergic turnover of the female rainbow trout (Oncorhynchus mykiss) at the beginning of vitellogenesis.", "content": "Brain serotonin and dopamine (DA) turnovers in the female rainbow trout were studied at the beginning of the vitellogenesis and related to blood estradiol (E2) levels; pituitary and plasma gonadotropin (GtH) were also assayed. Ovariectomy did not modify brain aminergic turnover. E2 replacement on ovariectomized fish increased hypothalamic DA turnover (increased DA and increased DA metabolites). E2 stimulated GtH synthesis (positive feedback) but did not enhance GtH release; hypothalamic E2-mediated aminergic inhibition upon release was suspected. Individual relations between blood E2 levels and catecholaminergic neurotransmitters were determined. A linear positive correlation (r = 0.82) was found for the hypothalamus, but not for the pituitary, the preoptic area, or the telencephalon. These data suggest that an activation of hypothalamic tyrosine hydroxylase (the limiting step of catecholamines synthesis) by E2 could develop as vitellogenesis proceeds.", "contents": "Effects of estradiol on brain aminergic turnover of the female rainbow trout (Oncorhynchus mykiss) at the beginning of vitellogenesis. Brain serotonin and dopamine (DA) turnovers in the female rainbow trout were studied at the beginning of the vitellogenesis and related to blood estradiol (E2) levels; pituitary and plasma gonadotropin (GtH) were also assayed. Ovariectomy did not modify brain aminergic turnover. E2 replacement on ovariectomized fish increased hypothalamic DA turnover (increased DA and increased DA metabolites). E2 stimulated GtH synthesis (positive feedback) but did not enhance GtH release; hypothalamic E2-mediated aminergic inhibition upon release was suspected. Individual relations between blood E2 levels and catecholaminergic neurotransmitters were determined. A linear positive correlation (r = 0.82) was found for the hypothalamus, but not for the pituitary, the preoptic area, or the telencephalon. These data suggest that an activation of hypothalamic tyrosine hydroxylase (the limiting step of catecholamines synthesis) by E2 could develop as vitellogenesis proceeds."} {"id": "PMID:1282482", "title": "Structural characterization of tachykinins (neuropeptide gamma, neurokinin A, and substance P) from a reptile, Alligator mississipiensis.", "content": "An extract of the whole brain of the alligator (Alligator mississipiensis) contained very high concentrations of substance P-like immunoreactivity (405 pmol/g wet tissue) and neurokinin A-like immunoreactivity (514 pmol/g), as measured with antisera raised against the mammalian peptides. The primary structure of alligator substance P was established as: Arg-Pro-Arg-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2. This sequence is the same as that of chicken substance P and shows one substitution (Arg for Lys3) as compared with mammalian substance P. The neurokinin A-like immunoreactivity was separated into two components. Neuropeptide gamma was the most abundant peptide and its primary structure was established as Asp-Ala-Gly-Tyr-Gly-Gln-Ile-Ser-His-Lys-Arg-His-Lys-Thr-Asp-Ser- Phe-Val-Gly-Leu-Met-NH2. This sequence shows one substitution (Tyr for His4) compared with mammalian neuropeptide gamma. The second component was identical to mammalian neurokinin A. A peptide with the chromatographic properties of mammalian neuropeptide K was not identified in the extract.", "contents": "Structural characterization of tachykinins (neuropeptide gamma, neurokinin A, and substance P) from a reptile, Alligator mississipiensis. An extract of the whole brain of the alligator (Alligator mississipiensis) contained very high concentrations of substance P-like immunoreactivity (405 pmol/g wet tissue) and neurokinin A-like immunoreactivity (514 pmol/g), as measured with antisera raised against the mammalian peptides. The primary structure of alligator substance P was established as: Arg-Pro-Arg-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2. This sequence is the same as that of chicken substance P and shows one substitution (Arg for Lys3) as compared with mammalian substance P. The neurokinin A-like immunoreactivity was separated into two components. Neuropeptide gamma was the most abundant peptide and its primary structure was established as Asp-Ala-Gly-Tyr-Gly-Gln-Ile-Ser-His-Lys-Arg-His-Lys-Thr-Asp-Ser- Phe-Val-Gly-Leu-Met-NH2. This sequence shows one substitution (Tyr for His4) compared with mammalian neuropeptide gamma. The second component was identical to mammalian neurokinin A. A peptide with the chromatographic properties of mammalian neuropeptide K was not identified in the extract."} {"id": "PMID:1282483", "title": "Misreading of the argI message in Escherichia coli.", "content": "It has previously been shown that either phenylalanine codon, UUU or UUC, could be misread as leucine during phenylalanine starvation, if the codons encoded residue 8 of the Escherichia coli argI gene product, ornithine transcarbamylase (OTC). However, no leucine misincorporation was detected when either of these same codons encoded residue 3. Here we report that leucine misincorporation can be directed by a UUU codon for residue 3 of OTC during phenylalanine starvation, if the argI gene has been mutated so that the codon preceding the UUU has been changed from the rarely used glycine codon GGG to the more commonly used GGC.", "contents": "Misreading of the argI message in Escherichia coli. It has previously been shown that either phenylalanine codon, UUU or UUC, could be misread as leucine during phenylalanine starvation, if the codons encoded residue 8 of the Escherichia coli argI gene product, ornithine transcarbamylase (OTC). However, no leucine misincorporation was detected when either of these same codons encoded residue 3. Here we report that leucine misincorporation can be directed by a UUU codon for residue 3 of OTC during phenylalanine starvation, if the argI gene has been mutated so that the codon preceding the UUU has been changed from the rarely used glycine codon GGG to the more commonly used GGC."} {"id": "PMID:1282484", "title": "How can peptide vaccines work?", "content": "Peptide antigens frequently induce antibodies which recognise the denatured form of a protein from which their sequences are derived. However, the ability to induce antibodies which crossreact with the native, fully folded form of the protein is less commonly observed. Although there is a growing number of examples in which this is the case, the ability to predict peptides having this property is extremely limited. Given the large surface areas involved in antibody/antigen interaction it is surprising that peptides could ever induce antibodies which would recognise the native protein well enough to have biological activity, such as the neutralization of infectivity. A mechanism is proposed to explain such observations which is compatible with many of the properties of antipeptide antibodies.", "contents": "How can peptide vaccines work? Peptide antigens frequently induce antibodies which recognise the denatured form of a protein from which their sequences are derived. However, the ability to induce antibodies which crossreact with the native, fully folded form of the protein is less commonly observed. Although there is a growing number of examples in which this is the case, the ability to predict peptides having this property is extremely limited. Given the large surface areas involved in antibody/antigen interaction it is surprising that peptides could ever induce antibodies which would recognise the native protein well enough to have biological activity, such as the neutralization of infectivity. A mechanism is proposed to explain such observations which is compatible with many of the properties of antipeptide antibodies."} {"id": "PMID:1282485", "title": "The conformational specificity of viral epitopes.", "content": "Four types of antigenic sites found in viruses are discussed: cryptotopes, neotopes, metatopes and neutralization epitopes. The role played by conformation on the specificity of viral epitopes is illustrated in the case of tobacco mosaic virus and influenza virus. It appears that mechanisms reminiscent of induced fit contribute to the recognition of viral epitopes by antibodies.", "contents": "The conformational specificity of viral epitopes. Four types of antigenic sites found in viruses are discussed: cryptotopes, neotopes, metatopes and neutralization epitopes. The role played by conformation on the specificity of viral epitopes is illustrated in the case of tobacco mosaic virus and influenza virus. It appears that mechanisms reminiscent of induced fit contribute to the recognition of viral epitopes by antibodies."} {"id": "PMID:1282486", "title": "Variation in O-antigens, niche-specific selection and bacterial populations.", "content": "Bacterial populations usually consist of distinct clones, often apparently adapted to specific niches. A formal model is developed whereby niche-specific selection maintains the polymorphisms involved in clonal adaptation. Infrequent transfer of non-adaptive alleles to a clone is balanced by the selection for the resident adaptive allele. The model can account for the extensive polymorphism in surface antigens observed in bacteria, and also for the existence of sympatric clones of pathogenic species which differ in host range and/or mode of pathogenesis. Niche-specific selection combined with low levels of genetic transfer can also account for the high level of neutral variation in bacteria, and indirectly for their ability to respond rapidly to environmental changes.", "contents": "Variation in O-antigens, niche-specific selection and bacterial populations. Bacterial populations usually consist of distinct clones, often apparently adapted to specific niches. A formal model is developed whereby niche-specific selection maintains the polymorphisms involved in clonal adaptation. Infrequent transfer of non-adaptive alleles to a clone is balanced by the selection for the resident adaptive allele. The model can account for the extensive polymorphism in surface antigens observed in bacteria, and also for the existence of sympatric clones of pathogenic species which differ in host range and/or mode of pathogenesis. Niche-specific selection combined with low levels of genetic transfer can also account for the high level of neutral variation in bacteria, and indirectly for their ability to respond rapidly to environmental changes."} {"id": "PMID:1282487", "title": "Identification of Staphylococcus epidermidis using a 16S rRNA-directed oligonucleotide probe.", "content": "Staphylococcus epidermidis is the most medically significant of the coagulase-negative staphylococci. An oligonucleotide probe (pSe) for identification of S. epidermidis was defined by comparing the sequences of the 16S rRNA variable region V6 from numerous coagulase-negative staphylococci. In order to increase the sensitivity of the detection, polymerase chain reaction amplification of the variable region with primers based on the conserved flanking sequences was applied. The detection limit of the polymerase chain reaction assay combined with pSe probe was shown to be 1 fg which corresponds to about one single bacterium. Additionally, a sensitive, non-radioisotopic system with chemiluminescence detection was tested.", "contents": "Identification of Staphylococcus epidermidis using a 16S rRNA-directed oligonucleotide probe. Staphylococcus epidermidis is the most medically significant of the coagulase-negative staphylococci. An oligonucleotide probe (pSe) for identification of S. epidermidis was defined by comparing the sequences of the 16S rRNA variable region V6 from numerous coagulase-negative staphylococci. In order to increase the sensitivity of the detection, polymerase chain reaction amplification of the variable region with primers based on the conserved flanking sequences was applied. The detection limit of the polymerase chain reaction assay combined with pSe probe was shown to be 1 fg which corresponds to about one single bacterium. Additionally, a sensitive, non-radioisotopic system with chemiluminescence detection was tested."} {"id": "PMID:1282488", "title": "DNA extraction for 16S rRNA gene analysis to determine genetic diversity in deep sediment communities.", "content": "A protocol was devised which permitted the extraction of DNA from deep marine sediments up to 503 m below the sea floor. These sediments have been laid down over the last 3 million years. 16S rRNA gene sequences were amplified from the DNA by the polymerase chain reaction. The details of the successful extraction and polymerase chain reaction methodology varied between samples from different depths. This emphasizes the attention to detail required to allow the diversity of bacteria in these deep sediments to be studied.", "contents": "DNA extraction for 16S rRNA gene analysis to determine genetic diversity in deep sediment communities. A protocol was devised which permitted the extraction of DNA from deep marine sediments up to 503 m below the sea floor. These sediments have been laid down over the last 3 million years. 16S rRNA gene sequences were amplified from the DNA by the polymerase chain reaction. The details of the successful extraction and polymerase chain reaction methodology varied between samples from different depths. This emphasizes the attention to detail required to allow the diversity of bacteria in these deep sediments to be studied."} {"id": "PMID:1282490", "title": "Platelet-induced thrombin generation time: a new sensitive global assay for platelet function and coagulation. Method and first results.", "content": "A new sensitive test--platelet-induced thrombin generation time (PITT)--is described, in which the formation of thrombin in partially anticoagulated platelet-rich plasma (PRP) leads to aggregation immediately followed by coagulation of PRP. 0.6 ml PRP are rotated in a disk-shaped cuvette within the light beam of a photometer. In PITT, platelets stick to the cuvette wall and, mediated by a large PRP/surface/air interface at the cuvette wall, are activated and participate in thrombin formation which leads to aggregation and clotting. The times from onset of rotation until aggregation (Ta) and until coagulation (Tc) of the PRP samples are recorded. PITT was very sensitive and detected low concentrations of unfractionated heparin (0.01 IU/ml) in vitro. PITT parameters were significantly prolonged ex vivo 2 h after oral administration of acetylsalicylic acid (0.5 g) and after single subcutaneous injections of heparin (5,000 IU). Patients receiving phenprocoumon prophylaxis had markedly prolonged Ta and Tc values (longer than 20 min, n = 23). Patients with recent thrombotic episodes had markedly shorter values than healthy volunteers. PITT may become a very sensitive global test to detect mild hemorrhagic disorders, to monitor the effects of antithrombotic drugs and to detect patients with a risk of vascular occlusions.", "contents": "Platelet-induced thrombin generation time: a new sensitive global assay for platelet function and coagulation. Method and first results. A new sensitive test--platelet-induced thrombin generation time (PITT)--is described, in which the formation of thrombin in partially anticoagulated platelet-rich plasma (PRP) leads to aggregation immediately followed by coagulation of PRP. 0.6 ml PRP are rotated in a disk-shaped cuvette within the light beam of a photometer. In PITT, platelets stick to the cuvette wall and, mediated by a large PRP/surface/air interface at the cuvette wall, are activated and participate in thrombin formation which leads to aggregation and clotting. The times from onset of rotation until aggregation (Ta) and until coagulation (Tc) of the PRP samples are recorded. PITT was very sensitive and detected low concentrations of unfractionated heparin (0.01 IU/ml) in vitro. PITT parameters were significantly prolonged ex vivo 2 h after oral administration of acetylsalicylic acid (0.5 g) and after single subcutaneous injections of heparin (5,000 IU). Patients receiving phenprocoumon prophylaxis had markedly prolonged Ta and Tc values (longer than 20 min, n = 23). Patients with recent thrombotic episodes had markedly shorter values than healthy volunteers. PITT may become a very sensitive global test to detect mild hemorrhagic disorders, to monitor the effects of antithrombotic drugs and to detect patients with a risk of vascular occlusions."} {"id": "PMID:1282491", "title": "Localization of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat to chromosome 4 and implications for the evolution of mammalian chromosomes.", "content": "We have isolated a partial cDNA encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat. This cDNA hybridizes to a 6.1-kb RNA transcript from the human T84 epithelial cell line and a similarly sized transcript from the rat parotid gland. The nucleotide sequence of this cDNA shows 80.5% identity to the human CFTR cDNA sequence, and the deduced amino acid sequence of rat CFTR shows 75.5% identity to the amino acid sequence of human CFTR. We have used this cDNA to map the location of the gene encoding CFTR to rat chromosome 4. This result places CFTR within a syntenic group on rat chromosome 4 and on human chromosome 7 that includes the genes encoding interleukin 6 (IL6), erythropoietin (EPO), P-glycoprotein 1 (PGY1), and T cell receptor beta chain (TCRB). This group is divided between chromosomes 5 and 6 in the mouse. Mapping of CFTR to rat chromosome 4 shows that this syntenic group has been divided in the mouse lineage during the past 15 million years and further localizes that breakpoint to a sequence homologous to the human chromosome 7q21.1 and 7q32 region. Similarly, a group of five genes, CFTR, TCRB, HOX1, parathyroid hormone-like hormone (PTHLH), and Kirsten rat sarcoma 2 viral (v-Ki-ras2) oncogene homolog (KRAS2), is syntenic on rat chromosome 4 and mouse chromosome 6, but is divided between human chromosomes 7 and 12. These data suggest that the ancestral mammalian chromosome appeared as the present day rat chromosome 4, with all six genes grouped together, and that chromosomal breakages have occurred in the mouse and human lineages since the mammalian divergence.", "contents": "Localization of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat to chromosome 4 and implications for the evolution of mammalian chromosomes. We have isolated a partial cDNA encoding the cystic fibrosis transmembrane conductance regulator (CFTR) in the rat. This cDNA hybridizes to a 6.1-kb RNA transcript from the human T84 epithelial cell line and a similarly sized transcript from the rat parotid gland. The nucleotide sequence of this cDNA shows 80.5% identity to the human CFTR cDNA sequence, and the deduced amino acid sequence of rat CFTR shows 75.5% identity to the amino acid sequence of human CFTR. We have used this cDNA to map the location of the gene encoding CFTR to rat chromosome 4. This result places CFTR within a syntenic group on rat chromosome 4 and on human chromosome 7 that includes the genes encoding interleukin 6 (IL6), erythropoietin (EPO), P-glycoprotein 1 (PGY1), and T cell receptor beta chain (TCRB). This group is divided between chromosomes 5 and 6 in the mouse. Mapping of CFTR to rat chromosome 4 shows that this syntenic group has been divided in the mouse lineage during the past 15 million years and further localizes that breakpoint to a sequence homologous to the human chromosome 7q21.1 and 7q32 region. Similarly, a group of five genes, CFTR, TCRB, HOX1, parathyroid hormone-like hormone (PTHLH), and Kirsten rat sarcoma 2 viral (v-Ki-ras2) oncogene homolog (KRAS2), is syntenic on rat chromosome 4 and mouse chromosome 6, but is divided between human chromosomes 7 and 12. These data suggest that the ancestral mammalian chromosome appeared as the present day rat chromosome 4, with all six genes grouped together, and that chromosomal breakages have occurred in the mouse and human lineages since the mammalian divergence."} {"id": "PMID:1282492", "title": "Conservation of a 23-kDa human transplantation antigen in mammalian species.", "content": "A group of transplantation antigens, referred to as tum- antigens, were identified in mouse tumor cells that had been mutagenized to produce variant cells and were recognized by clonal cytolytic T lymphocytes (CTL). Alterations in these variant cells that were recognized by CTL resulted from point mutations in the genes of specific proteins. We have isolated human and bovine cDNA clones that encode the homologs of the mouse tum- antigen P198. This 23.6-kDa protein is highly basic with a predicted pI of 11.55. p23/P198 is highly conserved across mammalian species, with > 94% identity (97% including conservative substitutions) among the human, bovine, and mouse deduced amino acid sequences. The nucleotide sequences of both the coding and 5'- and 3'-untranslated regions from human, bovine, and mouse are also highly conserved with > 88% identity in the coding regions. Hybridization of poly(A)+ RNA from various mammalian sources with cDNA and oligonucleotides specific for the coding region identified two mRNAs of 1.2 and 0.8 kb, whereas probes specific for the 3'-untranslated region between two consensus polyadenylation signals hybridized with the 1.2-kb, but not the 0.8-kb, mRNA. The abundance of the 1.2-kb mRNA relative to that of the 0.8-kb species varied depending upon the cell type. A single predominant transcription initiation site was mapped by primer extension. These studies indicate that this highly basic 23.6-kDa protein is encoded by two major mRNA species that differ only in the length of their 3'-untranslated regions and that the mechanism that gives rise to these two mRNAs, utilization of alternative polyadenylation sites, is conserved across species.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Conservation of a 23-kDa human transplantation antigen in mammalian species. A group of transplantation antigens, referred to as tum- antigens, were identified in mouse tumor cells that had been mutagenized to produce variant cells and were recognized by clonal cytolytic T lymphocytes (CTL). Alterations in these variant cells that were recognized by CTL resulted from point mutations in the genes of specific proteins. We have isolated human and bovine cDNA clones that encode the homologs of the mouse tum- antigen P198. This 23.6-kDa protein is highly basic with a predicted pI of 11.55. p23/P198 is highly conserved across mammalian species, with > 94% identity (97% including conservative substitutions) among the human, bovine, and mouse deduced amino acid sequences. The nucleotide sequences of both the coding and 5'- and 3'-untranslated regions from human, bovine, and mouse are also highly conserved with > 88% identity in the coding regions. Hybridization of poly(A)+ RNA from various mammalian sources with cDNA and oligonucleotides specific for the coding region identified two mRNAs of 1.2 and 0.8 kb, whereas probes specific for the 3'-untranslated region between two consensus polyadenylation signals hybridized with the 1.2-kb, but not the 0.8-kb, mRNA. The abundance of the 1.2-kb mRNA relative to that of the 0.8-kb species varied depending upon the cell type. A single predominant transcription initiation site was mapped by primer extension. These studies indicate that this highly basic 23.6-kDa protein is encoded by two major mRNA species that differ only in the length of their 3'-untranslated regions and that the mechanism that gives rise to these two mRNAs, utilization of alternative polyadenylation sites, is conserved across species.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282493", "title": "A delayed-type hypersensitivity-inducing T-cell epitope of Semliki Forest virus mediates effective T-helper activity for antibody production.", "content": "The rational development of peptide vaccines requires the identification of both B- and T-cell epitopes. In this study, potential T-helper cell epitopes of Semliki Forest virus (SFV) were identified on the basis of their ability to induce delayed-type hypersensitivity (DTH) in mice using recombinant SFV fragments produced as hybrid proteins with beta-galactosidase in Escherichia coli and synthetic peptides coupled to beta-galactosidase. Although the tested fragments spanned almost the entire amino acid sequence of the structural proteins of SFV, only one DTH-inducing region (located between amino acid 137 and 151 of the SFV E2 membrane protein) was identified. Peptides containing this E2 region stimulated lymph node cells from SFV-primed mice in vitro. The ability of the identified T-cell epitope to induce a specific T-helper response in mice was evaluated using synthetic peptides that contained combinations of the DTH-inducing region and different previously identified linear B-cell epitopes of E2. These peptides proved able to induce an antipeptide IgG response in mice in an H-2d-restricted fashion. One of the peptides was also able to induce high titres of IgG reactive with SFV-infected cells and protected 70-100% of the peptide-immunized mice after challenge with virulent SFV. Our findings suggest that DTH and T-helper activity are mediated by different doses of the same T-cell epitope.", "contents": "A delayed-type hypersensitivity-inducing T-cell epitope of Semliki Forest virus mediates effective T-helper activity for antibody production. The rational development of peptide vaccines requires the identification of both B- and T-cell epitopes. In this study, potential T-helper cell epitopes of Semliki Forest virus (SFV) were identified on the basis of their ability to induce delayed-type hypersensitivity (DTH) in mice using recombinant SFV fragments produced as hybrid proteins with beta-galactosidase in Escherichia coli and synthetic peptides coupled to beta-galactosidase. Although the tested fragments spanned almost the entire amino acid sequence of the structural proteins of SFV, only one DTH-inducing region (located between amino acid 137 and 151 of the SFV E2 membrane protein) was identified. Peptides containing this E2 region stimulated lymph node cells from SFV-primed mice in vitro. The ability of the identified T-cell epitope to induce a specific T-helper response in mice was evaluated using synthetic peptides that contained combinations of the DTH-inducing region and different previously identified linear B-cell epitopes of E2. These peptides proved able to induce an antipeptide IgG response in mice in an H-2d-restricted fashion. One of the peptides was also able to induce high titres of IgG reactive with SFV-infected cells and protected 70-100% of the peptide-immunized mice after challenge with virulent SFV. Our findings suggest that DTH and T-helper activity are mediated by different doses of the same T-cell epitope."} {"id": "PMID:1282494", "title": "Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP.", "content": "The effect of the neuropeptides substance P, neurokinin A and alpha-calcitonin gene-related peptide (CGRP) on human neutrophil granulocytes was investigated. Substance P induced secondary granule secretion at a concentration of 100 microM. CGRP induced a significant secretory response at 10 microM and thus appeared to be about 10 times more potent than substance P. Calcitonin and a fragment of CGRP, CGRP(8-37), had no effect on neutrophil degranulation. The chemotactic peptide antagonist BOC-MLP (100 microM) inhibited lactoferrin secretion mediated both by CGRP and chemotactic peptide FMLP almost completely, while secretion in response to tumour necrosis factor (TNF) was unaffected. Results from receptor binding studies showed that CGRP and N-formyl-methionyl-leucyl-phenylalanine (FMLP) do not compete for binding. This indicates that CGRP does not exert its effects by binding to the chemotactic peptide receptor. CGRP induced a rapid increase in the cytosolic-free calcium concentration and this increase was not, unlike that induced by FMLP, abolished by preincubation of the cells with pertussis toxin (1000 ng/ml). Therefore CGRP signal transduction in neutrophils appears to involve rapid changes in the cytosolic-free calcium concentration but not a pertussis toxin-sensitive G-protein. In summary, this is the first report to show that CGRP can directly activate neutrophil granulocytes, and this probably occurs via a cell surface receptor which is distinct from that of FMLP although both the CGRP and FMLP-mediated effects can be blocked by BOC-MLP.", "contents": "Calcitonin gene-related peptide (CGRP) activates human neutrophils--inhibition by chemotactic peptide antagonist BOC-MLP. The effect of the neuropeptides substance P, neurokinin A and alpha-calcitonin gene-related peptide (CGRP) on human neutrophil granulocytes was investigated. Substance P induced secondary granule secretion at a concentration of 100 microM. CGRP induced a significant secretory response at 10 microM and thus appeared to be about 10 times more potent than substance P. Calcitonin and a fragment of CGRP, CGRP(8-37), had no effect on neutrophil degranulation. The chemotactic peptide antagonist BOC-MLP (100 microM) inhibited lactoferrin secretion mediated both by CGRP and chemotactic peptide FMLP almost completely, while secretion in response to tumour necrosis factor (TNF) was unaffected. Results from receptor binding studies showed that CGRP and N-formyl-methionyl-leucyl-phenylalanine (FMLP) do not compete for binding. This indicates that CGRP does not exert its effects by binding to the chemotactic peptide receptor. CGRP induced a rapid increase in the cytosolic-free calcium concentration and this increase was not, unlike that induced by FMLP, abolished by preincubation of the cells with pertussis toxin (1000 ng/ml). Therefore CGRP signal transduction in neutrophils appears to involve rapid changes in the cytosolic-free calcium concentration but not a pertussis toxin-sensitive G-protein. In summary, this is the first report to show that CGRP can directly activate neutrophil granulocytes, and this probably occurs via a cell surface receptor which is distinct from that of FMLP although both the CGRP and FMLP-mediated effects can be blocked by BOC-MLP."} {"id": "PMID:1282495", "title": "Contribution of ICAM-1 and VCAM-1 to the morphological changes in monocytes bound to human venous endothelial cells stimulated with recombinant interleukin-4 (rIL-4) or rIL-1 alpha.", "content": "The present study focused on the question of whether the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of cultured human venous endothelial cells (EC), stimulated with recombinant interleukin-4 (rIL-4) or rIL-1 alpha, contributes to the stretching of human monocytes following their binding to EC. Stimulation of monolayers of venous EC with rIL-4 for 24 hr induced marked expression of VCAM-1 but not ICAM-1 on EC, increased the adhesiveness of EC for monocytes but did not promote stretching of EC-bound monocytes over the surface of EC. Stimulation of EC with rIL-1 alpha for 24 hr induced surface expression of both ICAM-1 and VCAM-1, enhanced the binding of monocytes to EC and increased the percentage of EC-bound monocytes with a stretched morphology about 2.7-fold. Anti-ICAM-1 but not anti-VCAM-1 mAb markedly reduced the percentage stretched monocytes on rIL-1 alpha-stimulated EC. We conclude that ICAM-1 but not VCAM-1 on cytokine-stimulated EC is essential for the stretching of EC-bound monocytes.", "contents": "Contribution of ICAM-1 and VCAM-1 to the morphological changes in monocytes bound to human venous endothelial cells stimulated with recombinant interleukin-4 (rIL-4) or rIL-1 alpha. The present study focused on the question of whether the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on the surface of cultured human venous endothelial cells (EC), stimulated with recombinant interleukin-4 (rIL-4) or rIL-1 alpha, contributes to the stretching of human monocytes following their binding to EC. Stimulation of monolayers of venous EC with rIL-4 for 24 hr induced marked expression of VCAM-1 but not ICAM-1 on EC, increased the adhesiveness of EC for monocytes but did not promote stretching of EC-bound monocytes over the surface of EC. Stimulation of EC with rIL-1 alpha for 24 hr induced surface expression of both ICAM-1 and VCAM-1, enhanced the binding of monocytes to EC and increased the percentage of EC-bound monocytes with a stretched morphology about 2.7-fold. Anti-ICAM-1 but not anti-VCAM-1 mAb markedly reduced the percentage stretched monocytes on rIL-1 alpha-stimulated EC. We conclude that ICAM-1 but not VCAM-1 on cytokine-stimulated EC is essential for the stretching of EC-bound monocytes."} {"id": "PMID:1282496", "title": "Hidden high-avidity anti-DNA antibodies occur in normal human gammaglobulin preparations.", "content": "An ability to detect hidden high-avidity DNA-binding protein in human gammaglobulin samples was investigated. Using ion exchange chromatography on QAE-Sephadex A-50 a highly positive Farr assay DNA-binding fraction was reproducibly isolated from several commercial normal human gammaglobulin preparations. The estimated dissociation constant had a value of 1.04 x 10(-11) M thus confirming high avidity protein-DNA complex formation. Anti-DNA antibodies (Ab) ELISA data revealed that immunoglobulin (Ig) G, IgM and IgA participated in the protein-DNA interaction. Inhibitory experiments involving a number of polynucleotides, synthetic and natural polyanions demonstrated that both double-stranded DNA (dsDNA) and heat-denatured DNA but not RNA inhibited the protein-3H-DNA binding. Generally, the inhibiting effect was more pronounced when purine base-containing polynucleotides and polydeoxy- rather than polyribonucleotides were used. Synthetic polyanions and normal human sera (NHS) also markedly reduced the binding. The presence of hidden high-avidity DNA-binding antibodies in normal gammaglobulin preparations was suggested.", "contents": "Hidden high-avidity anti-DNA antibodies occur in normal human gammaglobulin preparations. An ability to detect hidden high-avidity DNA-binding protein in human gammaglobulin samples was investigated. Using ion exchange chromatography on QAE-Sephadex A-50 a highly positive Farr assay DNA-binding fraction was reproducibly isolated from several commercial normal human gammaglobulin preparations. The estimated dissociation constant had a value of 1.04 x 10(-11) M thus confirming high avidity protein-DNA complex formation. Anti-DNA antibodies (Ab) ELISA data revealed that immunoglobulin (Ig) G, IgM and IgA participated in the protein-DNA interaction. Inhibitory experiments involving a number of polynucleotides, synthetic and natural polyanions demonstrated that both double-stranded DNA (dsDNA) and heat-denatured DNA but not RNA inhibited the protein-3H-DNA binding. Generally, the inhibiting effect was more pronounced when purine base-containing polynucleotides and polydeoxy- rather than polyribonucleotides were used. Synthetic polyanions and normal human sera (NHS) also markedly reduced the binding. The presence of hidden high-avidity DNA-binding antibodies in normal gammaglobulin preparations was suggested."} {"id": "PMID:1282497", "title": "Modulation of anti-acetylcholine receptor antibody specificities and of experimental autoimmune myasthenia gravis by synthetic peptides.", "content": "Synthetic peptides corresponding to selected sequences from the nicotinic acetylcholine receptor (AChR) were employed to identify possible antigenic determinants within the receptor which can modulate the anti-AChR response and experimental autoimmune myasthenia gravis (EAMG). Immunization of rabbits with peptides T alpha 73-89, T alpha 351-368, T delta 354-367 and H alpha 351-368, prior to AChR inoculation, affected the course of EAMG in six out of eight rabbits. These six protected rabbits survived three inoculations of AChR and survived for at least five months after the third injection with AChR, whereas control rabbits died following one or two injections of AChR. The survival of peptide-preimmunized rabbits injected with AChR seemed to correlate with the antibody specificities in immunoblots. Following AChR inoculation there was a shift in reactivity, from a subunit-restricted response, to reactivity with all subunits of the receptor. This shift was delayed in protected rabbits. This may indicate that the reactivity with the entire Torpedo receptor molecule represents a loss of tolerance to AChR which culminates in the autoimmune disease, EAMG.", "contents": "Modulation of anti-acetylcholine receptor antibody specificities and of experimental autoimmune myasthenia gravis by synthetic peptides. Synthetic peptides corresponding to selected sequences from the nicotinic acetylcholine receptor (AChR) were employed to identify possible antigenic determinants within the receptor which can modulate the anti-AChR response and experimental autoimmune myasthenia gravis (EAMG). Immunization of rabbits with peptides T alpha 73-89, T alpha 351-368, T delta 354-367 and H alpha 351-368, prior to AChR inoculation, affected the course of EAMG in six out of eight rabbits. These six protected rabbits survived three inoculations of AChR and survived for at least five months after the third injection with AChR, whereas control rabbits died following one or two injections of AChR. The survival of peptide-preimmunized rabbits injected with AChR seemed to correlate with the antibody specificities in immunoblots. Following AChR inoculation there was a shift in reactivity, from a subunit-restricted response, to reactivity with all subunits of the receptor. This shift was delayed in protected rabbits. This may indicate that the reactivity with the entire Torpedo receptor molecule represents a loss of tolerance to AChR which culminates in the autoimmune disease, EAMG."} {"id": "PMID:1282498", "title": "Immunoglobulin heavy and light chain gene sequences of a human CD5 positive immunocytoma and sequences of four novel VHIII germline genes.", "content": "To analyse the V genes expressed by an IgM lambda CD5-positive immunocytoma heavy and light chain V region genes were cloned and sequenced. The heavy chain is composed of a previously undescribed VHIII gene joined to an unknown D gene and to JH4. The light chain V region is composed of a V lambda II gene rearranged to J lambda 1. In an attempt to clone the germline counterpart of the VHIII gene expressed in the immunocytoma PCR amplifications of genomic DNA were carried out and four previously unknown VHIII genes were identified. As several independent clones for the heavy and light chain V region genes were sequenced the rate of somatic mutation of the V genes was calculated to be below 2 x 10(-5)/bp/cell division.", "contents": "Immunoglobulin heavy and light chain gene sequences of a human CD5 positive immunocytoma and sequences of four novel VHIII germline genes. To analyse the V genes expressed by an IgM lambda CD5-positive immunocytoma heavy and light chain V region genes were cloned and sequenced. The heavy chain is composed of a previously undescribed VHIII gene joined to an unknown D gene and to JH4. The light chain V region is composed of a V lambda II gene rearranged to J lambda 1. In an attempt to clone the germline counterpart of the VHIII gene expressed in the immunocytoma PCR amplifications of genomic DNA were carried out and four previously unknown VHIII genes were identified. As several independent clones for the heavy and light chain V region genes were sequenced the rate of somatic mutation of the V genes was calculated to be below 2 x 10(-5)/bp/cell division."} {"id": "PMID:1282499", "title": "Tumor necrosis factor-alpha stimulates both apical and basal production of HIV in polarized human intestinal HT29 cells.", "content": "The human colon epithelial cell line HT29 can be infected by selected strains of the human immunodeficiency virus (HIV) [9]. In the present study, it is shown that tumor necrosis factor-alpha (TNF-alpha) is a potent stimulator of HIV replication in chronically infected differentiated HT29 cells, but not in undifferentiated cells. The polarity of HIV production upon TNF-alpha stimulation has been studied in polarized monolayers of differentiated HT29 cells grown on porous-bottomed dishes. It is shown that the cytokine induced a dramatic increase of HIV production through the two opposite sides of the monolayer, i.e. the apical and basolateral plasma membrane domains. The effect of TNF-alpha was mainly localized at the level of viral mRNA synthesis as demonstrated by in situ hybridization. These data support the concept that cytokines released as a result of intestinal inflammatory responses could promote HIV replication and contribute to the gastrointestinal disease in HIV-infected patients.", "contents": "Tumor necrosis factor-alpha stimulates both apical and basal production of HIV in polarized human intestinal HT29 cells. The human colon epithelial cell line HT29 can be infected by selected strains of the human immunodeficiency virus (HIV) [9]. In the present study, it is shown that tumor necrosis factor-alpha (TNF-alpha) is a potent stimulator of HIV replication in chronically infected differentiated HT29 cells, but not in undifferentiated cells. The polarity of HIV production upon TNF-alpha stimulation has been studied in polarized monolayers of differentiated HT29 cells grown on porous-bottomed dishes. It is shown that the cytokine induced a dramatic increase of HIV production through the two opposite sides of the monolayer, i.e. the apical and basolateral plasma membrane domains. The effect of TNF-alpha was mainly localized at the level of viral mRNA synthesis as demonstrated by in situ hybridization. These data support the concept that cytokines released as a result of intestinal inflammatory responses could promote HIV replication and contribute to the gastrointestinal disease in HIV-infected patients."} {"id": "PMID:1282500", "title": "Different response of astrocytes and Bergmann glial cells to portacaval shunt: an immunohistochemical study in the rat cerebellum.", "content": "The present study was performed in order to follow the response of rat cerebellum astroglial cells (Bergmann glial cells and astrocytes) to long-term portacaval shunt (PCS), by means of glial fibrillary acidic protein (GFAP) and vimentin immunoreactivities. Bergmann glia accumulated GFAP in response to PCS, whereas astrocytes decreased GFAP immunoreactivity when compared to control rats. The increase of GFAP occurs in cells located in the cerebellar layer where glutamate is mainly released. Since the vimentin content remained unaltered in response to PCS, when compared to control rats, it can be concluded that only the GFAP filaments are affected by PCS. Nevertheless, GFAP immunoreactivity presents regional differences in the cerebellar astroglial population, and the factors responsible for these variations are still unknown.", "contents": "Different response of astrocytes and Bergmann glial cells to portacaval shunt: an immunohistochemical study in the rat cerebellum. The present study was performed in order to follow the response of rat cerebellum astroglial cells (Bergmann glial cells and astrocytes) to long-term portacaval shunt (PCS), by means of glial fibrillary acidic protein (GFAP) and vimentin immunoreactivities. Bergmann glia accumulated GFAP in response to PCS, whereas astrocytes decreased GFAP immunoreactivity when compared to control rats. The increase of GFAP occurs in cells located in the cerebellar layer where glutamate is mainly released. Since the vimentin content remained unaltered in response to PCS, when compared to control rats, it can be concluded that only the GFAP filaments are affected by PCS. Nevertheless, GFAP immunoreactivity presents regional differences in the cerebellar astroglial population, and the factors responsible for these variations are still unknown."} {"id": "PMID:1282501", "title": "Heterogeneity in gap junction expression in astrocytes cultured from different brain regions.", "content": "Heterogeneity among astrocytes suggests that their role in the central nervous system is more complex than is commonly recognized. This paper describes just such a functional difference, comparing gap junctions in astrocytes derived from two brain regions. Astrocytes, both in situ and in culture, employ gap junctions as a means of intercellular communication. Recent evidence utilizing cultured rat cortical and striatal astrocytes has shown that these channels consist of subunits of connexin 43, the same protein as that composing cardiac gap junctions. Here we report that astrocytes cultured from neonatal rat hypothalamus contain a greater number of functional channels than astrocytes from the striatum, a difference reflected in both connexin 43 protein and mRNA. Specifically, in hypothalamic astrocytes the level of connexin 43 protein was approximately four times that found in comparable cultures from the striatum, as determined by immunoblotting. Complementary results from immunocytochemical experiments using an antibody specific for connexin 43 reveal significantly greater fluorescence in astrocytes cultured from the hypothalamus as compared to those from the striatum. Northern blot analysis showed that connexin 43 mRNA levels were also approximately 4-fold greater in the hypothalamic cultures, consistent with the difference seen by immunoblotting. Finally, dye coupling studies using confluent cultures consistently showed that within 1 min Lucifer Yellow injected into striatal astrocytes spread to immediately surrounding cells while in hypothalamic astrocytes dye often spread to apparent third or fourth order neighbors within the same time period. Thus, the higher level of connexin 43 expression seen in hypothalamic astrocytes results in cells with greater numbers of functional channels.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Heterogeneity in gap junction expression in astrocytes cultured from different brain regions. Heterogeneity among astrocytes suggests that their role in the central nervous system is more complex than is commonly recognized. This paper describes just such a functional difference, comparing gap junctions in astrocytes derived from two brain regions. Astrocytes, both in situ and in culture, employ gap junctions as a means of intercellular communication. Recent evidence utilizing cultured rat cortical and striatal astrocytes has shown that these channels consist of subunits of connexin 43, the same protein as that composing cardiac gap junctions. Here we report that astrocytes cultured from neonatal rat hypothalamus contain a greater number of functional channels than astrocytes from the striatum, a difference reflected in both connexin 43 protein and mRNA. Specifically, in hypothalamic astrocytes the level of connexin 43 protein was approximately four times that found in comparable cultures from the striatum, as determined by immunoblotting. Complementary results from immunocytochemical experiments using an antibody specific for connexin 43 reveal significantly greater fluorescence in astrocytes cultured from the hypothalamus as compared to those from the striatum. Northern blot analysis showed that connexin 43 mRNA levels were also approximately 4-fold greater in the hypothalamic cultures, consistent with the difference seen by immunoblotting. Finally, dye coupling studies using confluent cultures consistently showed that within 1 min Lucifer Yellow injected into striatal astrocytes spread to immediately surrounding cells while in hypothalamic astrocytes dye often spread to apparent third or fourth order neighbors within the same time period. Thus, the higher level of connexin 43 expression seen in hypothalamic astrocytes results in cells with greater numbers of functional channels.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282503", "title": "Solid-phase synthesis of bovine pancreatic trypsin inhibitor (BPTI) and two analogues. A chemical approach for evaluating the role of disulfide bridges in protein folding and stability.", "content": "The linear sequence of bovine pancreatic trypsin inhibitor (BPTI) has been assembled by stepwise Fmoc solid-phase peptide synthesis on a polyethylene glycol-polystyrene (PEG-PS) graft support with p-alkoxybenzyl ester anchoring. Similar methods were used to prepare two analogues, the first with all six half-cystine (Cys) residues replaced by alpha-amino-n-butyric acid (Abu), and the second with replacement of Abu at four Cys positions while retaining the native pairing between positions 14 and 38. Following cleavage from the support, the linear molecules (reduced form) were purified by semipreparative reversed-phase high performance liquid chromatography (HPLC). The native structure of BPTI was then formed by oxidation of a dilute solution of the protein at pH 8.7 in the presence of oxidized glutathione. The BPTI analogue with one disulfide bridge was obtained following treatment with dimethyl sulfoxide (DMSO)-pH 6 buffer (1:9). Overall yields of homogeneous proteins were 2-4%, and further characterization was provided by amino acid analysis, sequencing, ion electrospray mass spectrometry, analytical HPLC, and capillary zone electrophoresis (CZE). Purified synthetic BPTI with the native sequence was indistinguishable from natural material by the analytical and biophysical criteria applied, including circular dichroism (CD) spectra and inhibition of trypsin action. Studies are in progress to evaluate conformational features of the analogues which respectively lack two, or all three, of the native disulfide bridges.", "contents": "Solid-phase synthesis of bovine pancreatic trypsin inhibitor (BPTI) and two analogues. A chemical approach for evaluating the role of disulfide bridges in protein folding and stability. The linear sequence of bovine pancreatic trypsin inhibitor (BPTI) has been assembled by stepwise Fmoc solid-phase peptide synthesis on a polyethylene glycol-polystyrene (PEG-PS) graft support with p-alkoxybenzyl ester anchoring. Similar methods were used to prepare two analogues, the first with all six half-cystine (Cys) residues replaced by alpha-amino-n-butyric acid (Abu), and the second with replacement of Abu at four Cys positions while retaining the native pairing between positions 14 and 38. Following cleavage from the support, the linear molecules (reduced form) were purified by semipreparative reversed-phase high performance liquid chromatography (HPLC). The native structure of BPTI was then formed by oxidation of a dilute solution of the protein at pH 8.7 in the presence of oxidized glutathione. The BPTI analogue with one disulfide bridge was obtained following treatment with dimethyl sulfoxide (DMSO)-pH 6 buffer (1:9). Overall yields of homogeneous proteins were 2-4%, and further characterization was provided by amino acid analysis, sequencing, ion electrospray mass spectrometry, analytical HPLC, and capillary zone electrophoresis (CZE). Purified synthetic BPTI with the native sequence was indistinguishable from natural material by the analytical and biophysical criteria applied, including circular dichroism (CD) spectra and inhibition of trypsin action. Studies are in progress to evaluate conformational features of the analogues which respectively lack two, or all three, of the native disulfide bridges."} {"id": "PMID:1282506", "title": "Human astroglial but not microglial cells synthesize alpha 2-macroglobulin in vitro.", "content": "Alpha 2-macroglobulin (alpha 2M) is a serum proteinase inhibitor with a broad specificity. At present its role in human brain is unknown, but recent data report its presence in the CNS, particularly at glial level. Previous studies from our group demonstrated the synthesis and secretion of alpha 2M in different glial cultures derived from an astrocytoma and a glioblastoma. In the present study a human fetal astroglial cell line and two microglial established cell lines are examined for the presence of alpha 2M by using polyclonal antibodies in ELISA and immunofluorescence assays. While we observed a strong specific positivity in the cytoplasm and in the culture medium of the GFAP, vimentine positive cells, no positivity was detected in FcR, lysozyme positive microglial cells. Since interaction of proteinases and proteinase inhibitors appear to play a crucial role in the development of neuroimmunological competence, these data suggest a dissociation of macro and micro-glia immune functions.", "contents": "Human astroglial but not microglial cells synthesize alpha 2-macroglobulin in vitro. Alpha 2-macroglobulin (alpha 2M) is a serum proteinase inhibitor with a broad specificity. At present its role in human brain is unknown, but recent data report its presence in the CNS, particularly at glial level. Previous studies from our group demonstrated the synthesis and secretion of alpha 2M in different glial cultures derived from an astrocytoma and a glioblastoma. In the present study a human fetal astroglial cell line and two microglial established cell lines are examined for the presence of alpha 2M by using polyclonal antibodies in ELISA and immunofluorescence assays. While we observed a strong specific positivity in the cytoplasm and in the culture medium of the GFAP, vimentine positive cells, no positivity was detected in FcR, lysozyme positive microglial cells. Since interaction of proteinases and proteinase inhibitors appear to play a crucial role in the development of neuroimmunological competence, these data suggest a dissociation of macro and micro-glia immune functions."} {"id": "PMID:1282504", "title": "Solid phase peptide synthesis of lipopeptide vaccines eliciting epitope-specific B-, T-helper and T-killer cell response.", "content": "Lymphocyte subpopulations involved in the self and nonself recognition processes are antibody producing cells, T-helper cells and T-killer cells. By using lipopeptide adjuvants and lipopeptide-antigen conjugates each of the major pathways of immune response can be specifically addressed on the molecular level of minimized synthetic lipopeptide vaccines. The immunologically active principle of the lipopeptide constructs is the synthetic N-terminus of bacterial lipoprotein, tri-palmitoyl-S-glycerylcysteine, which can be covalently linked to B-, T-helper and CTL epitopes. Methods of multiple peptide synthesis based on Merrifield's solid-phase synthesis allow the economic production of the high numbers of overlapping lipopeptides required for the complete immunological screening of viral proteins.", "contents": "Solid phase peptide synthesis of lipopeptide vaccines eliciting epitope-specific B-, T-helper and T-killer cell response. Lymphocyte subpopulations involved in the self and nonself recognition processes are antibody producing cells, T-helper cells and T-killer cells. By using lipopeptide adjuvants and lipopeptide-antigen conjugates each of the major pathways of immune response can be specifically addressed on the molecular level of minimized synthetic lipopeptide vaccines. The immunologically active principle of the lipopeptide constructs is the synthetic N-terminus of bacterial lipoprotein, tri-palmitoyl-S-glycerylcysteine, which can be covalently linked to B-, T-helper and CTL epitopes. Methods of multiple peptide synthesis based on Merrifield's solid-phase synthesis allow the economic production of the high numbers of overlapping lipopeptides required for the complete immunological screening of viral proteins."} {"id": "PMID:1282509", "title": "Expression of the carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15) in the vertebrate cerebellar cortex.", "content": "The distribution of the carbohydrate epitope CD15 was investigated on paraffin sections of the brains of man and mammals (monkey, dog, rabbit, rat, mouse, dolphin), reptile, bird and fish by means of immunohistochemistry. This paper demonstrates a differential expression of the CD15 epitope in the cerebella of these various vertebrates. CD15 positivity was found on glial cells and neuronal structures. In adult brains two major distribution patterns were distinguished: one with very intense labelling of the molecular layer, for which the rat is representative, the other with very low immunoreactivity in this layer (mouse). Amongst the rodents (mouse, rat and rabbit), as well as the monkey and human, the positivity in the molecular layer could be attributed to Bergmann fibres of the Golgi epithelial cells. A typical parasagittal band pattern, present in the mouse molecular layer for CD15, which is absent in rat and rabbit molecular layer, is present during human cerebellar development. CD15 positivity on neuronal structures is found on parallel fibres in the developing human, on the lower stellate cells in the dog, and in climbing fibres of the dolphin and, presumably, the catfish too. Moreover, within the parrot cerebellum, large CD15-positive mossy fibre-like endings are found just at the infraplexiform layer.", "contents": "Expression of the carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15) in the vertebrate cerebellar cortex. The distribution of the carbohydrate epitope CD15 was investigated on paraffin sections of the brains of man and mammals (monkey, dog, rabbit, rat, mouse, dolphin), reptile, bird and fish by means of immunohistochemistry. This paper demonstrates a differential expression of the CD15 epitope in the cerebella of these various vertebrates. CD15 positivity was found on glial cells and neuronal structures. In adult brains two major distribution patterns were distinguished: one with very intense labelling of the molecular layer, for which the rat is representative, the other with very low immunoreactivity in this layer (mouse). Amongst the rodents (mouse, rat and rabbit), as well as the monkey and human, the positivity in the molecular layer could be attributed to Bergmann fibres of the Golgi epithelial cells. A typical parasagittal band pattern, present in the mouse molecular layer for CD15, which is absent in rat and rabbit molecular layer, is present during human cerebellar development. CD15 positivity on neuronal structures is found on parallel fibres in the developing human, on the lower stellate cells in the dog, and in climbing fibres of the dolphin and, presumably, the catfish too. Moreover, within the parrot cerebellum, large CD15-positive mossy fibre-like endings are found just at the infraplexiform layer."} {"id": "PMID:1282507", "title": "Mast cell heterogeneity in man: unique functional properties of skin mast cells in response to a range of polycationic stimuli.", "content": "Human mast cell heterogeneity was assessed by histochemical and detailed functional criteria using mast cells isolated from foreskin, uterine myometrium and lung parenchyma. The skin mast cells were histochemically distinct from their counterparts in the other two tissues by being predominantly insensitive to blockage of dye-binding following formalin fixation (ca. 80%). Functionally, a wide range of structurally diverse polycationic compounds induced selective histamine release from the skin mast cells (ca. 10% at top concentrations) although these cells were less responsive to immunological ligands and calcium ionophores when compared with the uterine and lung cells. The basic compounds, polyarginine and histone, proved to be more generalised histamine liberators as compared with their structural analogues, polylysine and protamine sulphate, probably by virtue of their high content of arginine residues and hydrophobic nature (histone). Studies with the anaphylatoxin, C3a, and its analogues 21R and C3ades Arg on skin mast cells emphasized the importance of basic amino acids for histamine-liberating peptides. Skin mast cells also proved more susceptible than their uterine counterparts to lysis by the detergents, Triton X-100 and Tween 20, suggesting that fundamental differences in membrane structure and/or fluidity might account for functional heterogeneity within the human mast cell population.", "contents": "Mast cell heterogeneity in man: unique functional properties of skin mast cells in response to a range of polycationic stimuli. Human mast cell heterogeneity was assessed by histochemical and detailed functional criteria using mast cells isolated from foreskin, uterine myometrium and lung parenchyma. The skin mast cells were histochemically distinct from their counterparts in the other two tissues by being predominantly insensitive to blockage of dye-binding following formalin fixation (ca. 80%). Functionally, a wide range of structurally diverse polycationic compounds induced selective histamine release from the skin mast cells (ca. 10% at top concentrations) although these cells were less responsive to immunological ligands and calcium ionophores when compared with the uterine and lung cells. The basic compounds, polyarginine and histone, proved to be more generalised histamine liberators as compared with their structural analogues, polylysine and protamine sulphate, probably by virtue of their high content of arginine residues and hydrophobic nature (histone). Studies with the anaphylatoxin, C3a, and its analogues 21R and C3ades Arg on skin mast cells emphasized the importance of basic amino acids for histamine-liberating peptides. Skin mast cells also proved more susceptible than their uterine counterparts to lysis by the detergents, Triton X-100 and Tween 20, suggesting that fundamental differences in membrane structure and/or fluidity might account for functional heterogeneity within the human mast cell population."} {"id": "PMID:1282508", "title": "1-beta-D-arabinosylcytosine and 5-azacytidine induce internucleosomal DNA fragmentation and cell death in thymocytes.", "content": "Incubation of mouse thymocytes with arabinosylcytosine or 5-azacytidine induced dose-dependent internucleosomal DNA cleavage followed by cell death. This process was RNA and protein synthesis-dependent, since DNA fragmentation and cell death was inhibited by actinomycin D and cycloheximide. The results suggest that the cytidine analogs induce apoptosis, a programmed cell death, in thymocytes. The DNA cleavage induced by arabinosylcytosine and 5-azacytidine was inhibited by deoxycytidine and cytidine, respectively, suggesting that phosphorylation of these antimetabolites is required to induce DNA cleavage. DNA fragmentation was unaffected by the addition of aphidicolin or 3-aminobenzamide, indicating that DNA cleavage is not due to the inhibition of DNA synthesis or repair. Other antimetabolites including methotrexate, fluoropyrimidines and thiopurines failed to induce DNA fragmentation. Arabinosylguanine induced DNA fragmentation similar to that produced by the cytidine analogs, suggesting similarity to the selective sensitivity of T lymphocytes to deoxyguanosine toxicity. The precise mechanism by which DNA cleavage is induced remains unclear, but the present study shows that certain antimetabolites act on cells not only by inhibiting proliferation, but by inducing apoptosis with internucleosomal DNA fragmentation.", "contents": "1-beta-D-arabinosylcytosine and 5-azacytidine induce internucleosomal DNA fragmentation and cell death in thymocytes. Incubation of mouse thymocytes with arabinosylcytosine or 5-azacytidine induced dose-dependent internucleosomal DNA cleavage followed by cell death. This process was RNA and protein synthesis-dependent, since DNA fragmentation and cell death was inhibited by actinomycin D and cycloheximide. The results suggest that the cytidine analogs induce apoptosis, a programmed cell death, in thymocytes. The DNA cleavage induced by arabinosylcytosine and 5-azacytidine was inhibited by deoxycytidine and cytidine, respectively, suggesting that phosphorylation of these antimetabolites is required to induce DNA cleavage. DNA fragmentation was unaffected by the addition of aphidicolin or 3-aminobenzamide, indicating that DNA cleavage is not due to the inhibition of DNA synthesis or repair. Other antimetabolites including methotrexate, fluoropyrimidines and thiopurines failed to induce DNA fragmentation. Arabinosylguanine induced DNA fragmentation similar to that produced by the cytidine analogs, suggesting similarity to the selective sensitivity of T lymphocytes to deoxyguanosine toxicity. The precise mechanism by which DNA cleavage is induced remains unclear, but the present study shows that certain antimetabolites act on cells not only by inhibiting proliferation, but by inducing apoptosis with internucleosomal DNA fragmentation."} {"id": "PMID:1282510", "title": "Age-related expression patterns of the CD15 epitope in the human lateral geniculate nucleus (LGN).", "content": "The age-related distribution of the trisaccharide epitope 3-fucosyl-N-acetyl-lactosamine (CD15) was evaluated in the human lateral geniculate nucleus (LGN). Coronal paraffin sections from individuals between the 12th week of gestation to 99 years of age were processed for immunohistochemistry using monoclonal antibodies against the CD15 epitope. CD15 immunoreactivity was present in the neuropil from the 14th week of gestation with a graded pattern along the anteroposterior and mediolateral axes of the LGN. Immunoreactivity then became preferentially located within the future cell layers, shortly before cellular segregation was visible in Cresyl Violet stained sections. Maximal CD15 expression occurred from the 22nd week of gestation until the beginning of visual experience (second week of postnatal life). During the subsequent period the spatial pattern of CD15 expression changed. Whereas immunoreactivity in the cell layers gradually disappeared, CD15 positive astrocytes became transiently concentrated in the intercellular layers. The staining within the interlaminar region was best developed at about one year of postnatal life. The adult pattern was found at around 10 years of age, when the LGN appeared almost unstained. Two stages of CD15 expression can thus be separated. The first is characterized by neuropil staining and is synchronized with the time profile of neuronal maturation and of formation of non-stabilized contacts. CD15 is at this time possibly correlated with structural instability and increased vulnerability but at the same time with a high degree of plasticity. The second, peri- and postnatal stage is characterized by CD15 positive astrocytes. These appeared when CD15 in the neuropil disappeared. This loss of CD15 expression in the neuropil occurs during the phase of experience-dependent establishment of the mature interconnectivity and probably heralds loss in plasticity. The time-related expression pattern of CD15 is therefore compatible with the idea that CD15 levels reflect different degrees of developmental determination of retino-geniculate interaction.", "contents": "Age-related expression patterns of the CD15 epitope in the human lateral geniculate nucleus (LGN). The age-related distribution of the trisaccharide epitope 3-fucosyl-N-acetyl-lactosamine (CD15) was evaluated in the human lateral geniculate nucleus (LGN). Coronal paraffin sections from individuals between the 12th week of gestation to 99 years of age were processed for immunohistochemistry using monoclonal antibodies against the CD15 epitope. CD15 immunoreactivity was present in the neuropil from the 14th week of gestation with a graded pattern along the anteroposterior and mediolateral axes of the LGN. Immunoreactivity then became preferentially located within the future cell layers, shortly before cellular segregation was visible in Cresyl Violet stained sections. Maximal CD15 expression occurred from the 22nd week of gestation until the beginning of visual experience (second week of postnatal life). During the subsequent period the spatial pattern of CD15 expression changed. Whereas immunoreactivity in the cell layers gradually disappeared, CD15 positive astrocytes became transiently concentrated in the intercellular layers. The staining within the interlaminar region was best developed at about one year of postnatal life. The adult pattern was found at around 10 years of age, when the LGN appeared almost unstained. Two stages of CD15 expression can thus be separated. The first is characterized by neuropil staining and is synchronized with the time profile of neuronal maturation and of formation of non-stabilized contacts. CD15 is at this time possibly correlated with structural instability and increased vulnerability but at the same time with a high degree of plasticity. The second, peri- and postnatal stage is characterized by CD15 positive astrocytes. These appeared when CD15 in the neuropil disappeared. This loss of CD15 expression in the neuropil occurs during the phase of experience-dependent establishment of the mature interconnectivity and probably heralds loss in plasticity. The time-related expression pattern of CD15 is therefore compatible with the idea that CD15 levels reflect different degrees of developmental determination of retino-geniculate interaction."} {"id": "PMID:1282511", "title": "Expression of the CD15 epitope in the human magnocellular basal forebrain system.", "content": "The distribution of the carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15) has been immunocytochemically evaluated in coronal paraffin sections through the magnocellular basal forebrain system--the nucleus basalis of Meynert, the nucleus of the diagonal band of Broca and the medial septal nucleus--of 202 human brains. The brains derived from differently aged controls (n = 54) and from patients suffering from organic brain diseases (n = 129) or psychiatric disorders (n = 19). In 30 cases dementia was clinically diagnosed. CD15 first appeared around birth when it became localized on singular astrocytes. The astrocyte number and process density steadily increased, and at approximately 12 years the typical adult-type pattern was acquired. Considerable variations in the expression patterns were noted with regard to the astrocyte number, the intensity in immunostaining and the process relations of CD15-positive astrocytes with the magnocellular neurons. In the light of these variations, and of conflicting additional changes in other areas of most diseased brains, it was difficult to correlate different intensities and patterns to specific diseases. The results, however, provide evidence for an increase in CD15 expression and in process network density of astrocytes in the lateral part of the nucleus basalis of Meynert in cases of Huntington's disease.", "contents": "Expression of the CD15 epitope in the human magnocellular basal forebrain system. The distribution of the carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15) has been immunocytochemically evaluated in coronal paraffin sections through the magnocellular basal forebrain system--the nucleus basalis of Meynert, the nucleus of the diagonal band of Broca and the medial septal nucleus--of 202 human brains. The brains derived from differently aged controls (n = 54) and from patients suffering from organic brain diseases (n = 129) or psychiatric disorders (n = 19). In 30 cases dementia was clinically diagnosed. CD15 first appeared around birth when it became localized on singular astrocytes. The astrocyte number and process density steadily increased, and at approximately 12 years the typical adult-type pattern was acquired. Considerable variations in the expression patterns were noted with regard to the astrocyte number, the intensity in immunostaining and the process relations of CD15-positive astrocytes with the magnocellular neurons. In the light of these variations, and of conflicting additional changes in other areas of most diseased brains, it was difficult to correlate different intensities and patterns to specific diseases. The results, however, provide evidence for an increase in CD15 expression and in process network density of astrocytes in the lateral part of the nucleus basalis of Meynert in cases of Huntington's disease."} {"id": "PMID:1282512", "title": "Critical role of HLA-DR beta 1 residue 58 in multiple polymorphic epitopes recognized by xenogeneic and allogeneic antibodies.", "content": "In a previous study, we identified glutamic acid at position 58 in DR (beta 1*1101) as critical for the epitopes recognized by the DRw11-specific mAb GS88.2, as well as the I-LR1 mAb that recognizes a polymorphic epitope on DR(alpha,beta 1*1101) and some DP molecules. The purpose of this study was to determine whether other polymorphic residues contribute to these epitopes and whether DR beta glutamic acid or alanine 58 and DP beta glutamic acid 56, the analogous position in DP beta, contribute to epitopes recognized by other anti-class-II mAb and allosera. Site-directed mutagenesis and transfection were used to produce cells bearing wild-type or mutant class II molecules that were analyzed with mAbs by flow cytometry and with human allosera by absorption and subsequent microcytotoxicity assays. These studies demonstrate that the residue at DR beta position 58 plays a central role in at least three different mAb epitopes and an epitope recognized by anti-DRw11 allosera. Substitution of glutamic acid for alanine at position 58 of eight DR beta chains caused gain of binding of four mAbs to all of the mutant molecules, except DR(alpha,beta 4*0101). These data suggest that the side chains of DR beta 58 and DP beta 56 point outward from the alpha-helix and directly contact antibody.", "contents": "Critical role of HLA-DR beta 1 residue 58 in multiple polymorphic epitopes recognized by xenogeneic and allogeneic antibodies. In a previous study, we identified glutamic acid at position 58 in DR (beta 1*1101) as critical for the epitopes recognized by the DRw11-specific mAb GS88.2, as well as the I-LR1 mAb that recognizes a polymorphic epitope on DR(alpha,beta 1*1101) and some DP molecules. The purpose of this study was to determine whether other polymorphic residues contribute to these epitopes and whether DR beta glutamic acid or alanine 58 and DP beta glutamic acid 56, the analogous position in DP beta, contribute to epitopes recognized by other anti-class-II mAb and allosera. Site-directed mutagenesis and transfection were used to produce cells bearing wild-type or mutant class II molecules that were analyzed with mAbs by flow cytometry and with human allosera by absorption and subsequent microcytotoxicity assays. These studies demonstrate that the residue at DR beta position 58 plays a central role in at least three different mAb epitopes and an epitope recognized by anti-DRw11 allosera. Substitution of glutamic acid for alanine at position 58 of eight DR beta chains caused gain of binding of four mAbs to all of the mutant molecules, except DR(alpha,beta 4*0101). These data suggest that the side chains of DR beta 58 and DP beta 56 point outward from the alpha-helix and directly contact antibody."} {"id": "PMID:1282513", "title": "Purification and characterization of a novel thermostable lipase from Pseudomonas cepacia.", "content": "A thermostable lipase from Pseudomonas cepacia has been purified to homogeneity as judged by SDS-PAGE and isoelectric focusing. The purification included treatment of the culture supernatant with acrinol, hydrophobic interaction chromatography, and gel filtration. The enzyme was a monomeric protein with M(r) of 36,500 and pI of 5.1. The optimal pH at 50 degrees C and optimal temperature at pH 6.5 were 5.5-6.5 and 55-60 degrees C, respectively, when olive oil was used as the substrate. Simple triglycerides of short and middle chain fatty acids (C < or = 12) were the preferred substrates over those of long chain fatty acids. The enzyme cleaved all the ester bonds of triolein, with some preference for the 1,3-ester bonds. The enzyme retained all its activity even after incubation at 75 degrees C (pH 6.5) for 30 min. Further, the activity was not impaired during 21 h storage at pH 6.5 in 40% water-miscible solvents including methanol, ethanol, acetone, acetonitrile, dimethylformamide, dimethylsulfoxide, and dioxane. The addition of dimethylsulfoxide or acetone to the assay mixture in the range of 0-35% stimulated the enzyme, whereas benzene or n-hexane had an inhibitory effect. These properties together with the N-terminal amino acid sequence confirmed that the enzyme differs from the known Pseudomonas sp. lipases.", "contents": "Purification and characterization of a novel thermostable lipase from Pseudomonas cepacia. A thermostable lipase from Pseudomonas cepacia has been purified to homogeneity as judged by SDS-PAGE and isoelectric focusing. The purification included treatment of the culture supernatant with acrinol, hydrophobic interaction chromatography, and gel filtration. The enzyme was a monomeric protein with M(r) of 36,500 and pI of 5.1. The optimal pH at 50 degrees C and optimal temperature at pH 6.5 were 5.5-6.5 and 55-60 degrees C, respectively, when olive oil was used as the substrate. Simple triglycerides of short and middle chain fatty acids (C < or = 12) were the preferred substrates over those of long chain fatty acids. The enzyme cleaved all the ester bonds of triolein, with some preference for the 1,3-ester bonds. The enzyme retained all its activity even after incubation at 75 degrees C (pH 6.5) for 30 min. Further, the activity was not impaired during 21 h storage at pH 6.5 in 40% water-miscible solvents including methanol, ethanol, acetone, acetonitrile, dimethylformamide, dimethylsulfoxide, and dioxane. The addition of dimethylsulfoxide or acetone to the assay mixture in the range of 0-35% stimulated the enzyme, whereas benzene or n-hexane had an inhibitory effect. These properties together with the N-terminal amino acid sequence confirmed that the enzyme differs from the known Pseudomonas sp. lipases."} {"id": "PMID:1282515", "title": "Proliferation and differentiation of fetal rat intestinal epithelial cells in primary serum-free culture.", "content": "It has been a subject of controversy whether fibroblastic cells are necessary for the proliferation of intestinal epithelial cells in primary culture. To answer this question, we have developed a serum-free primary culture system which allows reproducible and quantitative assays of proliferation and differentiation of fetal rat intestinal epithelial cells in the absence of fibroblastic cells. Pure intestinal epithelial tissues were obtained from 16.5-day fetal rats without contamination of mesenchymal cells, and were successfully cultured on a collagen gel in a medium consisting of Ham's F12, bovine serum albumin, epidermal growth factor (EGF), insulin, cholera toxin, transferrin and hydrocortisone. The epithelial nature of the cultured cells was confirmed by the presence of cytokeratin in the cells. Under optimal culture conditions, intestinal epithelial cells readily attached to the substratum in a day, and proliferated rapidly in vitro, increasing their number about 10 times in the first 5 days. EGF, insulin, cholera toxin, transferrin and hydrocortisone synergistically induced the epithelial proliferation, and lack of any one of them resulted in a significant reduction of the proliferation. In contrast, fetal bovine or horse serums, which have been widely used to supplement culture media, severely inhibited the epithelial proliferation. Histological examination showed that the epithelial cells formed simple cuboidal epithelia with basally-located nuclei when cultured on collagen gels. The intestinal epithelial nature of the cells was affirmed by the presence of villin on their luminal surface. Ultrastructurally, cells were connected by tight junctions and desmosomes at the subluminal region, and microvilli were projecting on the luminal surface, indicating that the cells in primary culture retained some characteristics of absorptive epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Proliferation and differentiation of fetal rat intestinal epithelial cells in primary serum-free culture. It has been a subject of controversy whether fibroblastic cells are necessary for the proliferation of intestinal epithelial cells in primary culture. To answer this question, we have developed a serum-free primary culture system which allows reproducible and quantitative assays of proliferation and differentiation of fetal rat intestinal epithelial cells in the absence of fibroblastic cells. Pure intestinal epithelial tissues were obtained from 16.5-day fetal rats without contamination of mesenchymal cells, and were successfully cultured on a collagen gel in a medium consisting of Ham's F12, bovine serum albumin, epidermal growth factor (EGF), insulin, cholera toxin, transferrin and hydrocortisone. The epithelial nature of the cultured cells was confirmed by the presence of cytokeratin in the cells. Under optimal culture conditions, intestinal epithelial cells readily attached to the substratum in a day, and proliferated rapidly in vitro, increasing their number about 10 times in the first 5 days. EGF, insulin, cholera toxin, transferrin and hydrocortisone synergistically induced the epithelial proliferation, and lack of any one of them resulted in a significant reduction of the proliferation. In contrast, fetal bovine or horse serums, which have been widely used to supplement culture media, severely inhibited the epithelial proliferation. Histological examination showed that the epithelial cells formed simple cuboidal epithelia with basally-located nuclei when cultured on collagen gels. The intestinal epithelial nature of the cells was affirmed by the presence of villin on their luminal surface. Ultrastructurally, cells were connected by tight junctions and desmosomes at the subluminal region, and microvilli were projecting on the luminal surface, indicating that the cells in primary culture retained some characteristics of absorptive epithelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282516", "title": "Tenascin in bone morphogenesis: expression by osteoblasts and cell type-specific expression of splice variants.", "content": "The extracellular matrix glycoprotein, tenascin, is associated in vivo with mesenchyme undergoing osteogenesis and chondrogenesis, but is absent from mature bone and cartilage matrix. The expression of tenascin by osteoblastic cells in vitro has been investigated by immunoblotting and immunocytochemistry. Tenascin was secreted into the medium and deposited in the matrix by human and rat osteoblast-like cell lines, as well as by primary osteoblast-enriched cultures from chick embryo calvarial bones. In primary osteoblast-enriched cultures, extracellular tenascin was found only in cell aggregates expressing the osteoblast marker alkaline phosphatase. Chicken osteoblast cultures synthesized almost exclusively the largest tenascin subunit, whereas fibroblast cultures from periostea of chicken calvariae synthesized approximately equal amounts of all three subunits. In situ hybridization studies of developing chicken bones, using a cDNA probe that hybridizes to all chicken tenascin splice variants, showed specific labelling of both osteogenic and chondrogenic regions of developing endochondral bones. In contrast, a cDNA probe specific for the large tenascin splice variant showed specific hybridization in osteogenic but not chondrogenic regions. Within osteogenic regions, tenascin mRNA was expressed by osteoblasts. A comparison of in situ hybridization and immunohistochemical studies demonstrated that tenascin mRNA and protein were codistributed in osteogenic regions of endochondral and membrane bones, whereas protein was retained in regions of differentiating cartilage where mRNA was no longer detectable. The results presented here demonstrate that tenascin is synthesized by osteoblasts. Moreover, within developing bones, there are at least three different cell type-specific patterns of expression of tenascin splice variants.", "contents": "Tenascin in bone morphogenesis: expression by osteoblasts and cell type-specific expression of splice variants. The extracellular matrix glycoprotein, tenascin, is associated in vivo with mesenchyme undergoing osteogenesis and chondrogenesis, but is absent from mature bone and cartilage matrix. The expression of tenascin by osteoblastic cells in vitro has been investigated by immunoblotting and immunocytochemistry. Tenascin was secreted into the medium and deposited in the matrix by human and rat osteoblast-like cell lines, as well as by primary osteoblast-enriched cultures from chick embryo calvarial bones. In primary osteoblast-enriched cultures, extracellular tenascin was found only in cell aggregates expressing the osteoblast marker alkaline phosphatase. Chicken osteoblast cultures synthesized almost exclusively the largest tenascin subunit, whereas fibroblast cultures from periostea of chicken calvariae synthesized approximately equal amounts of all three subunits. In situ hybridization studies of developing chicken bones, using a cDNA probe that hybridizes to all chicken tenascin splice variants, showed specific labelling of both osteogenic and chondrogenic regions of developing endochondral bones. In contrast, a cDNA probe specific for the large tenascin splice variant showed specific hybridization in osteogenic but not chondrogenic regions. Within osteogenic regions, tenascin mRNA was expressed by osteoblasts. A comparison of in situ hybridization and immunohistochemical studies demonstrated that tenascin mRNA and protein were codistributed in osteogenic regions of endochondral and membrane bones, whereas protein was retained in regions of differentiating cartilage where mRNA was no longer detectable. The results presented here demonstrate that tenascin is synthesized by osteoblasts. Moreover, within developing bones, there are at least three different cell type-specific patterns of expression of tenascin splice variants."} {"id": "PMID:1282517", "title": "Determination of risperidone and 9-hydroxyrisperidone in plasma, urine and animal tissues by high-performance liquid chromatography.", "content": "A high-performance liquid chromatographic method has been developed for the simultaneous determination of the new antipsychotic risperidone and its major metabolite 9-hydroxyrisperidone in plasma, urine and animal tissues. The alkalinized plasma samples were extracted with ethyl acetate and further purified prior to reversed-phase chromatography with ultraviolet detection at 280 nm. The method could also be applied to urine samples and animal tissue homogenates. Quantification limits were 2 ng/ml for plasma and urine and 10 ng/g for animal tissue. The method was applied to pharmacokinetic studies in experimental animals, human volunteers and patients.", "contents": "Determination of risperidone and 9-hydroxyrisperidone in plasma, urine and animal tissues by high-performance liquid chromatography. A high-performance liquid chromatographic method has been developed for the simultaneous determination of the new antipsychotic risperidone and its major metabolite 9-hydroxyrisperidone in plasma, urine and animal tissues. The alkalinized plasma samples were extracted with ethyl acetate and further purified prior to reversed-phase chromatography with ultraviolet detection at 280 nm. The method could also be applied to urine samples and animal tissue homogenates. Quantification limits were 2 ng/ml for plasma and urine and 10 ng/g for animal tissue. The method was applied to pharmacokinetic studies in experimental animals, human volunteers and patients."} {"id": "PMID:1282518", "title": "Smooth muscle dilatation in the human uterine artery induced by substance P, vasoactive intestinal polypeptide, calcitonin gene-related peptide and atrial natriuretic peptide: relation to endothelium-derived relaxing substances.", "content": "The relaxatory influences of substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) were investigated in human uterine arteries precontracted by noradrenaline in vitro. SP, VIP, CGRP and ANP all relaxed isolated uterine arteries with intact endothelium. When tested on vessels devoid of their endothelium VIP and SP had no effect on smooth muscular tone, while ANP and CGRP still induced unchanged vasodilatation. These results suggest an involvement of an endothelium-derived relaxing substance in the mechanisms by which VIP and SP induce relaxation of the isolated human uterine artery. On the other hand, ANP and CGRP seem to act on the same vessel preparation in vitro independently of the vascular endothelium. Both addition of noradrenaline and exchange of sodium against potassium in the organ chambers resulted in smooth muscle contraction irrespective of the integrity of the endothelium.", "contents": "Smooth muscle dilatation in the human uterine artery induced by substance P, vasoactive intestinal polypeptide, calcitonin gene-related peptide and atrial natriuretic peptide: relation to endothelium-derived relaxing substances. The relaxatory influences of substance P (SP), vasoactive intestinal polypeptide (VIP), calcitonin gene-related peptide (CGRP) and atrial natriuretic peptide (ANP) were investigated in human uterine arteries precontracted by noradrenaline in vitro. SP, VIP, CGRP and ANP all relaxed isolated uterine arteries with intact endothelium. When tested on vessels devoid of their endothelium VIP and SP had no effect on smooth muscular tone, while ANP and CGRP still induced unchanged vasodilatation. These results suggest an involvement of an endothelium-derived relaxing substance in the mechanisms by which VIP and SP induce relaxation of the isolated human uterine artery. On the other hand, ANP and CGRP seem to act on the same vessel preparation in vitro independently of the vascular endothelium. Both addition of noradrenaline and exchange of sodium against potassium in the organ chambers resulted in smooth muscle contraction irrespective of the integrity of the endothelium."} {"id": "PMID:1282519", "title": "Dot blot immunoassay for detection of human semen.", "content": "A sensitive and specific dot blot immunoassay based on prostate specific antigen (PSA) antibodies and a radiolabelled Protein A detection system was developed for detection of trace amounts of human semen in stains. The method was found highly sensitive and detected semen stain extracts diluted 10,000 times. Semen stains up to five years old were successfully detected by the method. The assay is found to be highly suitable for semen detection in forensic analysis.", "contents": "Dot blot immunoassay for detection of human semen. A sensitive and specific dot blot immunoassay based on prostate specific antigen (PSA) antibodies and a radiolabelled Protein A detection system was developed for detection of trace amounts of human semen in stains. The method was found highly sensitive and detected semen stain extracts diluted 10,000 times. Semen stains up to five years old were successfully detected by the method. The assay is found to be highly suitable for semen detection in forensic analysis."} {"id": "PMID:1282520", "title": "DNA fingerprints of Helicobacter pylori before and after treatment with omeprazole.", "content": "To test whether a hypoacidic environment may potentially \"stress\" Helicobacter pylori DNA, encouraging the emergence of strain variation. This hypothesis was tested by inducing prolonged hypoacidity with omeprazole, a potent antisecretory drug. The genomic DNA of H pylori was studied by electrophoretic separation of restriction endonuclease fragments followed by rRNA gene hybridisation in seven patients infected with H pylori before and after treatment with omeprazole 20-40 mg daily for six to eight weeks. DNA was isolated and purified using the guanidium thiocyanate reagent method. DNA samples were digested with Hae III, electrophoresed, vacublotted, and hybridised using a biotinylated cDNA probe prepared from 16S and 23S rRNA from H pylori NCTC 11638. Isolates were compared using their ribopatterns (DNA fingerprints). A total of 26 isolates were obtained; all DNA isolates were cut by Hae III, which was the enzyme that gave the best resolved hybridisation patterns for analysis. No two patients harboured the same strain. The isolates from two patients showed evidence of subtypic variation; one patient had two distinct strains and four patients had their own indistinguishable strains before and after treatment with omeprazole. For each patient, the paired ribopatterns of H pylori DNA were not affected by treatment with omeprazole for six to eight weeks. The H pylori genome is relatively stable when exposed to the conditions of prolonged hypoacidity that result from treatment with omeprazole.", "contents": "DNA fingerprints of Helicobacter pylori before and after treatment with omeprazole. To test whether a hypoacidic environment may potentially \"stress\" Helicobacter pylori DNA, encouraging the emergence of strain variation. This hypothesis was tested by inducing prolonged hypoacidity with omeprazole, a potent antisecretory drug. The genomic DNA of H pylori was studied by electrophoretic separation of restriction endonuclease fragments followed by rRNA gene hybridisation in seven patients infected with H pylori before and after treatment with omeprazole 20-40 mg daily for six to eight weeks. DNA was isolated and purified using the guanidium thiocyanate reagent method. DNA samples were digested with Hae III, electrophoresed, vacublotted, and hybridised using a biotinylated cDNA probe prepared from 16S and 23S rRNA from H pylori NCTC 11638. Isolates were compared using their ribopatterns (DNA fingerprints). A total of 26 isolates were obtained; all DNA isolates were cut by Hae III, which was the enzyme that gave the best resolved hybridisation patterns for analysis. No two patients harboured the same strain. The isolates from two patients showed evidence of subtypic variation; one patient had two distinct strains and four patients had their own indistinguishable strains before and after treatment with omeprazole. For each patient, the paired ribopatterns of H pylori DNA were not affected by treatment with omeprazole for six to eight weeks. The H pylori genome is relatively stable when exposed to the conditions of prolonged hypoacidity that result from treatment with omeprazole."} {"id": "PMID:1282521", "title": "Evaluation of three techniques for differential diagnosis of prostatic needle biopsy specimens.", "content": "To determine whether acidic mucin staining, lectin histochemistry using Wisteria floribunda agglutinin, and immunohistochemistry using the monoclonal antibody EAB 903 are of benefit in distinguishing between hyperplastic and carcinomatous prostatic glandular tissue in needle biopsy specimens. Formalin fixed, paraffin wax embedded prostatic needle biopsy specimens of benign and malignant tissue were examined. Alcian blue-periodic acid Schiff staining was performed on 33 benign and 34 malignant cases. Wisteria floribunda agglutinin (WFA) binding sites were demonstrated by the avidin-biotin peroxidase (ABC) technique with and without neuraminidase pretreatment on 34 benign cases and 32 malignant cases. EAB903 anticytokeratin antibody binding sites were demonstrated using both an indirect immunoperoxidase (IIP) technique and an avidin-biotin peroxidase complex method on seven benign and 31 malignant cases. Acidic mucin staining was found in 17 of 34 malignant glands and was weakly positive in five of 33 benign glands. WFA positivity before neuraminidase pretreatment was present in 29 of 32 malignant glands and in 19 of 34 benign glands. After neuraminidase all benign and malignant cases showed positivity. EAB 903 positivity was seen in 11 of 31 malignant glands using the IIP technique and in two of 31 malignant glands using the ABC technique. In seven benign cases there was positivity in all glands using the IIP method with predominant basal cell staining in three and superficial cell staining in four. In benign cases using the ABC method two cases were negative. None of the three methods studied showed sufficient sensitivity and specificity to allow their recommendation for routine diagnostic use.", "contents": "Evaluation of three techniques for differential diagnosis of prostatic needle biopsy specimens. To determine whether acidic mucin staining, lectin histochemistry using Wisteria floribunda agglutinin, and immunohistochemistry using the monoclonal antibody EAB 903 are of benefit in distinguishing between hyperplastic and carcinomatous prostatic glandular tissue in needle biopsy specimens. Formalin fixed, paraffin wax embedded prostatic needle biopsy specimens of benign and malignant tissue were examined. Alcian blue-periodic acid Schiff staining was performed on 33 benign and 34 malignant cases. Wisteria floribunda agglutinin (WFA) binding sites were demonstrated by the avidin-biotin peroxidase (ABC) technique with and without neuraminidase pretreatment on 34 benign cases and 32 malignant cases. EAB903 anticytokeratin antibody binding sites were demonstrated using both an indirect immunoperoxidase (IIP) technique and an avidin-biotin peroxidase complex method on seven benign and 31 malignant cases. Acidic mucin staining was found in 17 of 34 malignant glands and was weakly positive in five of 33 benign glands. WFA positivity before neuraminidase pretreatment was present in 29 of 32 malignant glands and in 19 of 34 benign glands. After neuraminidase all benign and malignant cases showed positivity. EAB 903 positivity was seen in 11 of 31 malignant glands using the IIP technique and in two of 31 malignant glands using the ABC technique. In seven benign cases there was positivity in all glands using the IIP method with predominant basal cell staining in three and superficial cell staining in four. In benign cases using the ABC method two cases were negative. None of the three methods studied showed sufficient sensitivity and specificity to allow their recommendation for routine diagnostic use."} {"id": "PMID:1282522", "title": "Monoamine oxidase inhibitors phenelzine and brofaromine increase plasma serotonin and decrease 5-hydroxyindoleacetic acid in patients with major depression: relationship to clinical improvement.", "content": "We have examined the effects of two monoamine oxidase (MAO) inhibitors with different mechanisms of action--phenelzine and brofaromine--on peripheral serotonergic (5-hydroxytryptamine [5-HT]) measures, sensitive to the inhibition of MAO-A (intra- and extracellular 5-HT and related metabolites in blood). Both drugs increased the concentration of 5-HT in platelet-free plasma (254%, p less than 0.001) in patients with depressive illness (DSM-III-R) after 6 weeks of daily treatment. Platelet 5-HT was also increased significantly in both drug treatment groups but more marked in the patient group treated with phenelzine. The acid/amine ratio at 6 weeks was 30% of pretreatment values (p less than 0.000) and individual variability correlated significantly with the Hamilton Rating Scale for Depression. Plasma 5-HT increased more markedly in responders than in nonresponders and a significant inverse relationship surfaced between plasma 5-HT and the Hamilton Rating Scale for Depression. The results support other reports of comparable antidepressant efficacy for brofaromine and phenelzine, both inhibitors of MAO-A in humans. The consistent relationship we found between the biochemical and clinical changes again suggests and supports a key role of 5-HT in the antidepressant effect of these MAO inhibitors.", "contents": "Monoamine oxidase inhibitors phenelzine and brofaromine increase plasma serotonin and decrease 5-hydroxyindoleacetic acid in patients with major depression: relationship to clinical improvement. We have examined the effects of two monoamine oxidase (MAO) inhibitors with different mechanisms of action--phenelzine and brofaromine--on peripheral serotonergic (5-hydroxytryptamine [5-HT]) measures, sensitive to the inhibition of MAO-A (intra- and extracellular 5-HT and related metabolites in blood). Both drugs increased the concentration of 5-HT in platelet-free plasma (254%, p less than 0.001) in patients with depressive illness (DSM-III-R) after 6 weeks of daily treatment. Platelet 5-HT was also increased significantly in both drug treatment groups but more marked in the patient group treated with phenelzine. The acid/amine ratio at 6 weeks was 30% of pretreatment values (p less than 0.000) and individual variability correlated significantly with the Hamilton Rating Scale for Depression. Plasma 5-HT increased more markedly in responders than in nonresponders and a significant inverse relationship surfaced between plasma 5-HT and the Hamilton Rating Scale for Depression. The results support other reports of comparable antidepressant efficacy for brofaromine and phenelzine, both inhibitors of MAO-A in humans. The consistent relationship we found between the biochemical and clinical changes again suggests and supports a key role of 5-HT in the antidepressant effect of these MAO inhibitors."} {"id": "PMID:1282523", "title": "Galanin receptors in the brain of a teleost: autoradiographic distribution of binding sites in the Atlantic salmon.", "content": "The distribution of galanin (GAL) binding sites in the brain of the Atlantic salmon (Salmo salar) was investigated by means of radioligand binding in conjunction with autoradiography by using high-performance liquid chromatography (HPLC) characterized radio-iodinated porcine galanin ([125I]GAL). On slide-mounted sections of frozen salmon brain homogenate, [125I]GAL (4 nM) bound rapidly and reversibly to a single population of sites with a Kd of 1.0 +/- 0.08 nM (n = 3) and Bmax of 2.38 +/- 0.19 fmol/mg wet tissue. Specific [125I]GAL binding was found in cellular regions, in fiber tracts, and in neuropil areas throughout the brain, except for in the olfactory bulb, pineal organ, and cerebellum. Autoradiographic microdensitometric measurements revealed high total [125I]GAL binding in the ventral hypothalamus (inferior lobes; around 7-12 fmol/mg tissue), the dorsal spinal cord (between 6 and 12 fmol/mg tissue), sublayers of the optic tectum (around 8 fmol/mg), torus semicircularis (around 7 fmol/mg), and glomerular complex (around 6 fmol/mg). Intermediate densities of [125I]GAL binding (3-5 fmol/mg tissue) were found in the pituitary, telencephalon, dorsolateral thalamic nucleus, and raphe nuclei and in association with the forebrain bundles. Except for in the optic tectum, there is a good concordance of [125I]GAL binding sites and GAL-immunoreactive fiber projections in most brain areas of the salmon. The wide distribution of GAL binding sites provides further evidence that a GAL-like substance might be involved in a diversity of brain functions of teleosts. The topographic distribution of target sites in the hypothalamo-hypophyseal axis indicates that GAL-like substances may have both direct and indirect effect on pituitary functions while in extrahypothalamic areas, functional implications by GAL may include involvement in somatosensory, central gustatory, olfactory, and visual functions. This study provides evidence for the presence of a specific GAL receptor in the brain of the Atlantic salmon. Together the distribution of GAL binding and GAL-like molecules provide a covering delineation of the GAL neuronal system in the brain of the Atlantic salmon. Comparisons with mammals suggest that the GAL receptor molecule has been well preserved during evolution and that GAL-like substances may be present, and even possess similar functional properties, throughout the vertebrate phylogeny.", "contents": "Galanin receptors in the brain of a teleost: autoradiographic distribution of binding sites in the Atlantic salmon. The distribution of galanin (GAL) binding sites in the brain of the Atlantic salmon (Salmo salar) was investigated by means of radioligand binding in conjunction with autoradiography by using high-performance liquid chromatography (HPLC) characterized radio-iodinated porcine galanin ([125I]GAL). On slide-mounted sections of frozen salmon brain homogenate, [125I]GAL (4 nM) bound rapidly and reversibly to a single population of sites with a Kd of 1.0 +/- 0.08 nM (n = 3) and Bmax of 2.38 +/- 0.19 fmol/mg wet tissue. Specific [125I]GAL binding was found in cellular regions, in fiber tracts, and in neuropil areas throughout the brain, except for in the olfactory bulb, pineal organ, and cerebellum. Autoradiographic microdensitometric measurements revealed high total [125I]GAL binding in the ventral hypothalamus (inferior lobes; around 7-12 fmol/mg tissue), the dorsal spinal cord (between 6 and 12 fmol/mg tissue), sublayers of the optic tectum (around 8 fmol/mg), torus semicircularis (around 7 fmol/mg), and glomerular complex (around 6 fmol/mg). Intermediate densities of [125I]GAL binding (3-5 fmol/mg tissue) were found in the pituitary, telencephalon, dorsolateral thalamic nucleus, and raphe nuclei and in association with the forebrain bundles. Except for in the optic tectum, there is a good concordance of [125I]GAL binding sites and GAL-immunoreactive fiber projections in most brain areas of the salmon. The wide distribution of GAL binding sites provides further evidence that a GAL-like substance might be involved in a diversity of brain functions of teleosts. The topographic distribution of target sites in the hypothalamo-hypophyseal axis indicates that GAL-like substances may have both direct and indirect effect on pituitary functions while in extrahypothalamic areas, functional implications by GAL may include involvement in somatosensory, central gustatory, olfactory, and visual functions. This study provides evidence for the presence of a specific GAL receptor in the brain of the Atlantic salmon. Together the distribution of GAL binding and GAL-like molecules provide a covering delineation of the GAL neuronal system in the brain of the Atlantic salmon. Comparisons with mammals suggest that the GAL receptor molecule has been well preserved during evolution and that GAL-like substances may be present, and even possess similar functional properties, throughout the vertebrate phylogeny."} {"id": "PMID:1282524", "title": "Postnatal development of area 17 callosal connections in Tupaia.", "content": "The goal of the present study was to investigate the pattern of maturation of callosal projecting neurons in a well-studied mammalian visual system with unique structural and functional properties. Studies of the distribution pattern of interhemispheric connections in the adult tree shrew primary visual cortex reveal not only a high concentration of labeled neurons along the area 17/18 border, as in standard experimental animals such as the cat and monkey, but also numerous callosal projecting neurons in the adjacent dorsal part of area 17, which largely corresponds to the binocular visual field (Kretz and Rager, Exp. Brain Res. 82:271, '90). Callosal projections were anatomically traced in 11 tree shrews (Tupaia belangeri) at various ages between postnatal day 7 (7, 9, 10, 13, 15, 17, 19, and 26 days old) and adulthood (107 days old). In each animal, four injections of wheat germ agglutinin conjugated to horseradish peroxidase were made in a standard configuration into the striate cortex of one hemisphere. In young tree shrews only 7 and 9 days old, heavily labeled terminal axon structures could be seen in the white matter and in layer VI of the opposite hemisphere. Only a few labeled neurons, however, were detected in layer III. The small number of labeled neurons indicated that early in postnatal development, only a few callosal axons had invaded the upper cortical layers. By 10 days of age, the number of supragranular neurons was increasing and the maximal value was counted in a 13-day-old tree shrew. A sharp decline in the number of labeled supragranular neurons was noticed--about 94% in our case--between days 13 and 15. In animals more than 15 days old, the distribution pattern and the density of the neurons looked like the pattern seen in the adult Tupaia brain. The labeled cells were mostly concentrated in layers II and III. The majority of neurons resembled typical pyramidal cells. However, some of the neurons in sublayer IIIc had elongated cell bodies oriented parallel to the laminar boundaries. In contrast to the supragranular cells found in all stages investigated, small populations of labeled cells in layer VI were observed in 9- to 17-day-old tree shrews only. In young postnatal animals 7 to 13 days old, a peculiar cell type was labeled on the ipsilateral side. In coronal sections these cell bodies formed a continuous band that extended from the ventricular wall to the subcortical white matter. These cells might belong to a population of cells still in migration.", "contents": "Postnatal development of area 17 callosal connections in Tupaia. The goal of the present study was to investigate the pattern of maturation of callosal projecting neurons in a well-studied mammalian visual system with unique structural and functional properties. Studies of the distribution pattern of interhemispheric connections in the adult tree shrew primary visual cortex reveal not only a high concentration of labeled neurons along the area 17/18 border, as in standard experimental animals such as the cat and monkey, but also numerous callosal projecting neurons in the adjacent dorsal part of area 17, which largely corresponds to the binocular visual field (Kretz and Rager, Exp. Brain Res. 82:271, '90). Callosal projections were anatomically traced in 11 tree shrews (Tupaia belangeri) at various ages between postnatal day 7 (7, 9, 10, 13, 15, 17, 19, and 26 days old) and adulthood (107 days old). In each animal, four injections of wheat germ agglutinin conjugated to horseradish peroxidase were made in a standard configuration into the striate cortex of one hemisphere. In young tree shrews only 7 and 9 days old, heavily labeled terminal axon structures could be seen in the white matter and in layer VI of the opposite hemisphere. Only a few labeled neurons, however, were detected in layer III. The small number of labeled neurons indicated that early in postnatal development, only a few callosal axons had invaded the upper cortical layers. By 10 days of age, the number of supragranular neurons was increasing and the maximal value was counted in a 13-day-old tree shrew. A sharp decline in the number of labeled supragranular neurons was noticed--about 94% in our case--between days 13 and 15. In animals more than 15 days old, the distribution pattern and the density of the neurons looked like the pattern seen in the adult Tupaia brain. The labeled cells were mostly concentrated in layers II and III. The majority of neurons resembled typical pyramidal cells. However, some of the neurons in sublayer IIIc had elongated cell bodies oriented parallel to the laminar boundaries. In contrast to the supragranular cells found in all stages investigated, small populations of labeled cells in layer VI were observed in 9- to 17-day-old tree shrews only. In young postnatal animals 7 to 13 days old, a peculiar cell type was labeled on the ipsilateral side. In coronal sections these cell bodies formed a continuous band that extended from the ventricular wall to the subcortical white matter. These cells might belong to a population of cells still in migration."} {"id": "PMID:1282525", "title": "Immunofluorescent analysis of creatine kinase in cultured astrocytes by conventional and confocal microscopy: a nuclear localization.", "content": "The subcellular localization of creatine kinase (CK) was examined in primary cultures of astrocytes with immunofluorescent labeling methods and detection by both standard fluorescence microscopy and confocal laser-scanning microscopy. With conventional microscopy, the pattern of CK staining was uniform throughout the cell cytoplasm and appeared to stain the nuclear region intensely. Staining of CK in the nuclear region co-localized with the DNA-specific Hoechst nuclear stain. CK produced a diffuse cytoplasmic staining pattern that was different from the staining pattern produced by the cytoskeletal proteins glial fibrillary acidic protein and tubulin, both of which showed a filamentous cytoskeletal network that excluded the nucleus. To examine the structural details of CK in the nuclear region, serial optical sections were taken through the cell monolayer with a confocal microscope. The cells were immunostained for CK, and the CK-staining pattern was compared with the staining pattern produced by propidium iodide, which is specific for DNA in RNase-treated samples and stains total nucleic acid in untreated samples. CK staining was present within the nucleus in each section taken through the monolayer. The nucleolus did not stain for CK. The pattern of CK staining in the nucleus (and cytoplasm) was distinctly different from the staining pattern of either DNA or total nucleic acid. Nuclear CK appeared to have a granular, particulate pattern, which is suggestive of a nucleoplasmic distribution.", "contents": "Immunofluorescent analysis of creatine kinase in cultured astrocytes by conventional and confocal microscopy: a nuclear localization. The subcellular localization of creatine kinase (CK) was examined in primary cultures of astrocytes with immunofluorescent labeling methods and detection by both standard fluorescence microscopy and confocal laser-scanning microscopy. With conventional microscopy, the pattern of CK staining was uniform throughout the cell cytoplasm and appeared to stain the nuclear region intensely. Staining of CK in the nuclear region co-localized with the DNA-specific Hoechst nuclear stain. CK produced a diffuse cytoplasmic staining pattern that was different from the staining pattern produced by the cytoskeletal proteins glial fibrillary acidic protein and tubulin, both of which showed a filamentous cytoskeletal network that excluded the nucleus. To examine the structural details of CK in the nuclear region, serial optical sections were taken through the cell monolayer with a confocal microscope. The cells were immunostained for CK, and the CK-staining pattern was compared with the staining pattern produced by propidium iodide, which is specific for DNA in RNase-treated samples and stains total nucleic acid in untreated samples. CK staining was present within the nucleus in each section taken through the monolayer. The nucleolus did not stain for CK. The pattern of CK staining in the nucleus (and cytoplasm) was distinctly different from the staining pattern of either DNA or total nucleic acid. Nuclear CK appeared to have a granular, particulate pattern, which is suggestive of a nucleoplasmic distribution."} {"id": "PMID:1282526", "title": "Immunohistochemical and ultrastructural characterization of tonofilament and hemidesmosome abnormalities in a case of epidermolysis bullosa herpetiformis (Dowling-Meara).", "content": "A neonate with epidermolysis bullosa herpetiformis (EBH) (Dowling-Meara) had an undescribed ultrastructural and immunohistochemical abnormality. The objective was to clarify the ultrastructural and immunohistochemical abnormalities in EBH to gain further insight into the pathogenesis of this disorder. Tissue from the patient was studied with routine histochemistry, electron microscopy, and immunohistochemistry. Excessive clumping of tonofilaments on electron microscopic examination, anomalous hemidesmosomes, and immunohistochemical evidence of aberrant keratin expression by basal epidermal cells was found. This case of EBH provides further evidence for primary abnormalities involving cytoskeletal-membrane attachment plaque formation in this rare disorder.", "contents": "Immunohistochemical and ultrastructural characterization of tonofilament and hemidesmosome abnormalities in a case of epidermolysis bullosa herpetiformis (Dowling-Meara). A neonate with epidermolysis bullosa herpetiformis (EBH) (Dowling-Meara) had an undescribed ultrastructural and immunohistochemical abnormality. The objective was to clarify the ultrastructural and immunohistochemical abnormalities in EBH to gain further insight into the pathogenesis of this disorder. Tissue from the patient was studied with routine histochemistry, electron microscopy, and immunohistochemistry. Excessive clumping of tonofilaments on electron microscopic examination, anomalous hemidesmosomes, and immunohistochemical evidence of aberrant keratin expression by basal epidermal cells was found. This case of EBH provides further evidence for primary abnormalities involving cytoskeletal-membrane attachment plaque formation in this rare disorder."} {"id": "PMID:1282527", "title": "Erythema multiforme: pathomechanism of papular erythema and target lesion.", "content": "Skin lesions of erythema multiforme show time-dependent changes from early papular erythema to the late target lesion which consists of a peripheral elevated erythematous area and a central depressed area. We investigated the pathomechanism of erythema multiforme, by examining the papular erythema and target lesion separately. In the early papular erythema, a small number of polymorphonuclear leukocytes and nuclear debris were seen intermingled with mononuclear cells around the slightly swollen blood vessels, on which immunoglobulin and complement components were deposited. Circulating immune complex levels were occasionally elevated. Sera from the patients generated high levels of reactive oxygen species and nitroblue tetrazolium test revealed positive reaction on the infiltrating cells around the blood vessels. These findings suggest that the papular erythema develops via incomplete type III allergic reaction, followed by damage through reactive oxygen species. In the target lesion, the activity of histamine-N-methyltransferase, which is the major histamine-degrading enzyme, was markedly decreased in the peripheral elevated erythematous area and it was recovering in the central clearing area. ICAM-1 and HLA-DR antigens were expressed on the surfaces of the keratinocytes. An increased number of epidermal Langerhans cells and CD4 cell infiltration were observed in the peripheral elevated erythematous area, while a decreased number of epidermal Langerhans cells and CD8 cell infiltration in the central depressed area were observed. These findings suggest that impaired histamine metabolism and cellular allergic reactions play important roles in the development of the target lesion.", "contents": "Erythema multiforme: pathomechanism of papular erythema and target lesion. Skin lesions of erythema multiforme show time-dependent changes from early papular erythema to the late target lesion which consists of a peripheral elevated erythematous area and a central depressed area. We investigated the pathomechanism of erythema multiforme, by examining the papular erythema and target lesion separately. In the early papular erythema, a small number of polymorphonuclear leukocytes and nuclear debris were seen intermingled with mononuclear cells around the slightly swollen blood vessels, on which immunoglobulin and complement components were deposited. Circulating immune complex levels were occasionally elevated. Sera from the patients generated high levels of reactive oxygen species and nitroblue tetrazolium test revealed positive reaction on the infiltrating cells around the blood vessels. These findings suggest that the papular erythema develops via incomplete type III allergic reaction, followed by damage through reactive oxygen species. In the target lesion, the activity of histamine-N-methyltransferase, which is the major histamine-degrading enzyme, was markedly decreased in the peripheral elevated erythematous area and it was recovering in the central clearing area. ICAM-1 and HLA-DR antigens were expressed on the surfaces of the keratinocytes. An increased number of epidermal Langerhans cells and CD4 cell infiltration were observed in the peripheral elevated erythematous area, while a decreased number of epidermal Langerhans cells and CD8 cell infiltration in the central depressed area were observed. These findings suggest that impaired histamine metabolism and cellular allergic reactions play important roles in the development of the target lesion."} {"id": "PMID:1282528", "title": "Ultrastructure of Golgi-impregnated and gold-toned neurons in the central nucleus of the inferior colliculus in the cat.", "content": "The combined Golgi/electron microscope technique was used to analyse the cytoarchitecture and the fine structure of the central nucleus of the inferior colliculus in the cat. The analysis of Golgi-impregnated sections discriminates three major neuronal types, according to somato-dendritic morphology, and to presence or absence of dendritic spines. Two major types (spiny and aspiny) might be further subdivided into large, medium-large, medium-small and small, whilst the third (\"mixed\") type is subdivided into large and medium-large types. The large, medium-large and medium-small cells of the major types appear to be efferent (relay) neurons, whilst the small spiny, and especially the small aspiny cells are interneurons. In agreement with previous data, the subdivision of the relay neurons in disc-shaped and stellate cells is confirmed but the disc-shaped neurons are further subdivided in typical and atypical. The dendritic fields of the latter neurons correspond greatly but not exclusively to the fibrodendritic laminae of the central nucleus. In addition to the axonal ramification of the local circuit neurons, the axons of most (if not all) types of relay cells emit a moderate to scant, rarely--a substantial number of collaterals. The collaterals of the large spiny neurons (atypical disc-shaped cells) occasionally innervate also the cell of origin. Parallel to the light microscopic discriminations of the different neuronal types, the electron microscopic observations confirm that the ultrastructural characteristics might be very distinct. Especially evident are the differences between the large neuronal types, concerning the amount and arrangement of the granular endoplasmic reticulum, and the mode of the perikaryal, dendritic, and axonal innervation by various synaptic bouton types. Along with the unequivocal discrimination of the neurons in the central nucleus of the inferior colliculus according to the dendritic orientation, we suggest also a more detailed classification of the neuronal types according to the perikaryal size, fine dendritic morphology, and ultrastructural characteristics. Further hodological experiments, combined with the presently explored technique, will help to clarify the complicated synaptic events in the central nucleus of the inferior colliculus.", "contents": "Ultrastructure of Golgi-impregnated and gold-toned neurons in the central nucleus of the inferior colliculus in the cat. The combined Golgi/electron microscope technique was used to analyse the cytoarchitecture and the fine structure of the central nucleus of the inferior colliculus in the cat. The analysis of Golgi-impregnated sections discriminates three major neuronal types, according to somato-dendritic morphology, and to presence or absence of dendritic spines. Two major types (spiny and aspiny) might be further subdivided into large, medium-large, medium-small and small, whilst the third (\"mixed\") type is subdivided into large and medium-large types. The large, medium-large and medium-small cells of the major types appear to be efferent (relay) neurons, whilst the small spiny, and especially the small aspiny cells are interneurons. In agreement with previous data, the subdivision of the relay neurons in disc-shaped and stellate cells is confirmed but the disc-shaped neurons are further subdivided in typical and atypical. The dendritic fields of the latter neurons correspond greatly but not exclusively to the fibrodendritic laminae of the central nucleus. In addition to the axonal ramification of the local circuit neurons, the axons of most (if not all) types of relay cells emit a moderate to scant, rarely--a substantial number of collaterals. The collaterals of the large spiny neurons (atypical disc-shaped cells) occasionally innervate also the cell of origin. Parallel to the light microscopic discriminations of the different neuronal types, the electron microscopic observations confirm that the ultrastructural characteristics might be very distinct. Especially evident are the differences between the large neuronal types, concerning the amount and arrangement of the granular endoplasmic reticulum, and the mode of the perikaryal, dendritic, and axonal innervation by various synaptic bouton types. Along with the unequivocal discrimination of the neurons in the central nucleus of the inferior colliculus according to the dendritic orientation, we suggest also a more detailed classification of the neuronal types according to the perikaryal size, fine dendritic morphology, and ultrastructural characteristics. Further hodological experiments, combined with the presently explored technique, will help to clarify the complicated synaptic events in the central nucleus of the inferior colliculus."} {"id": "PMID:1282529", "title": "Influence of spinal cord hemisection on the configurational changes in motor and primary afferent neurons and the chemical messenger alterations in the rat lumbar segments.", "content": "Cholera toxin B subunit (CTB), a retrograde transport marker, was injected into the rat gastrocnemius muscles, and changes in CTB-labeling pattern of motoneurons and primary afferent neurons at the level L4 and L5 after spinal cord hemisection of the L1 level were observed in conjunction with the alterations of chemical messengers such as serotonin (5-HT), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (Gal), Met-enkephalin (Enk), and neuropeptide Y (NPY). Motoneurons at the L4 and L5 levels on the lesioned side exhibited significant shrinkage of their dendritic arbors without apparent loss of their number throughout all stages from 1 to 12 weeks after the hemisection of the spinal cord. Postoperatively, central processes of neuron of the dorsal root ganglia (DRG) on the lesioned side increased progressively compared to that on the contralateral side with the passage of time. The percentage of CTB-labeled neurons in the DRG has been consistently smaller in number on the lesioned side after the operation, and the difference between sides became more apparent during the later postoperative stages. 5-HT-containing fibers in the anterior and posterior horns on the lesioned side showed a significant decrease in the number, while no apparent changes were observed in the distribution of nerve fibers containing CGRP, SP, Gal, Enk, and NPY.", "contents": "Influence of spinal cord hemisection on the configurational changes in motor and primary afferent neurons and the chemical messenger alterations in the rat lumbar segments. Cholera toxin B subunit (CTB), a retrograde transport marker, was injected into the rat gastrocnemius muscles, and changes in CTB-labeling pattern of motoneurons and primary afferent neurons at the level L4 and L5 after spinal cord hemisection of the L1 level were observed in conjunction with the alterations of chemical messengers such as serotonin (5-HT), calcitonin gene-related peptide (CGRP), substance P (SP), galanin (Gal), Met-enkephalin (Enk), and neuropeptide Y (NPY). Motoneurons at the L4 and L5 levels on the lesioned side exhibited significant shrinkage of their dendritic arbors without apparent loss of their number throughout all stages from 1 to 12 weeks after the hemisection of the spinal cord. Postoperatively, central processes of neuron of the dorsal root ganglia (DRG) on the lesioned side increased progressively compared to that on the contralateral side with the passage of time. The percentage of CTB-labeled neurons in the DRG has been consistently smaller in number on the lesioned side after the operation, and the difference between sides became more apparent during the later postoperative stages. 5-HT-containing fibers in the anterior and posterior horns on the lesioned side showed a significant decrease in the number, while no apparent changes were observed in the distribution of nerve fibers containing CGRP, SP, Gal, Enk, and NPY."} {"id": "PMID:1282530", "title": "Maturation of neurons in neocortical slice cultures: A light and electron microscopic study on in situ and in vitro material.", "content": "Using light and electron microscopic methods, we investigated the development and morphology of neurons in neocortical slice cultures. Slices taken from the visual cortex of 6-day-old rats and cultivated for 14 or 20 days were compared with in situ material of corresponding age (P 20 and P 26). Maturation and differentiation of pyramidal and non-pyramidal cells kept in vitro were found to have progressed considerably. In the light microscope the neurons exhibited a morphological appearance strikingly similar to that of the neurons of the neocortex in situ at the same age. The fine structure of the tissue in vitro also had a mature appearance, corresponding in most respects to the material in situ. Synapses and dendritic spines were well-developed. Sometimes a spine apparatus was contained in the sections and occasionally a myelinated fiber could be seen. GABA-immunoreactive cells making symmetric synaptic contacts were also present. Despite these similarities, some quantitative differences could be observed. In slice cultures, only 52% of the synapses were located on spines (78% in situ). In vitro, a larger proportion of synapses (30%) showed a postsynaptically concave curvature than was the case in situ (12%). The areal density of synapses in vitro reached only about 70% of that in situ. This was probably a side-effect of the larger size of dendritic and axonal profiles on electron micrographs of in vitro-material. The most striking difference was that large synapses and synapses containing a large amount of synaptic vesicles were considerably more frequent in vitro than in situ.", "contents": "Maturation of neurons in neocortical slice cultures: A light and electron microscopic study on in situ and in vitro material. Using light and electron microscopic methods, we investigated the development and morphology of neurons in neocortical slice cultures. Slices taken from the visual cortex of 6-day-old rats and cultivated for 14 or 20 days were compared with in situ material of corresponding age (P 20 and P 26). Maturation and differentiation of pyramidal and non-pyramidal cells kept in vitro were found to have progressed considerably. In the light microscope the neurons exhibited a morphological appearance strikingly similar to that of the neurons of the neocortex in situ at the same age. The fine structure of the tissue in vitro also had a mature appearance, corresponding in most respects to the material in situ. Synapses and dendritic spines were well-developed. Sometimes a spine apparatus was contained in the sections and occasionally a myelinated fiber could be seen. GABA-immunoreactive cells making symmetric synaptic contacts were also present. Despite these similarities, some quantitative differences could be observed. In slice cultures, only 52% of the synapses were located on spines (78% in situ). In vitro, a larger proportion of synapses (30%) showed a postsynaptically concave curvature than was the case in situ (12%). The areal density of synapses in vitro reached only about 70% of that in situ. This was probably a side-effect of the larger size of dendritic and axonal profiles on electron micrographs of in vitro-material. The most striking difference was that large synapses and synapses containing a large amount of synaptic vesicles were considerably more frequent in vitro than in situ."} {"id": "PMID:1282531", "title": "Evidence for the existence of a projection from the dorsal column nuclei to the substantia nigra in the cat.", "content": "Discrete injections of horseradish peroxidase in the substantia nigra of cats resulted in moderate to scant retrograde neuronal labeling of the contralateral dorsal column nuclei (nucleus gracilis and nucleus cuneatus). A moderate number of degenerating synaptic boutons emanating from the axons of stereotaxically lesioned dorsal column nuclei were identified by electron microscopy in the neuropil of the contralateral substantia nigra zona compacta and its dorsal division-nucleus parabrachialis pigmentosus. The present findings furnish evidence for a moderate, entirely crossed afferent projection of the dopaminergic neurons of the mesencephalic tegmentum, arising in the dorsal column nuclei.", "contents": "Evidence for the existence of a projection from the dorsal column nuclei to the substantia nigra in the cat. Discrete injections of horseradish peroxidase in the substantia nigra of cats resulted in moderate to scant retrograde neuronal labeling of the contralateral dorsal column nuclei (nucleus gracilis and nucleus cuneatus). A moderate number of degenerating synaptic boutons emanating from the axons of stereotaxically lesioned dorsal column nuclei were identified by electron microscopy in the neuropil of the contralateral substantia nigra zona compacta and its dorsal division-nucleus parabrachialis pigmentosus. The present findings furnish evidence for a moderate, entirely crossed afferent projection of the dopaminergic neurons of the mesencephalic tegmentum, arising in the dorsal column nuclei."} {"id": "PMID:1282532", "title": "Subicular efferents to histaminergic neurons in the posterior hypothalamic region of the rat studied with PHA-L tracing combined with histidine decarboxylase immunocytochemistry.", "content": "The projections from the subiculum to histaminergic cells in the posterior hypothalamic region of the rat were studied by means of anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L) combined with histidine decarboxylase (HDC)-immunohistochemistry. PHA-L was injected at various loci along the dorsoventral and proximodistal axes of the subiculum. This resulted in labeling of the fornix and of terminal plexuses at various locations in the diencephalon and the mammillary body. Following deposition of PHA-L in the proximal part of the dorsal subiculum, labeled fibers in the posterior hypothalamus were confined to the mammillary nuclei, whereas after injections of PHA-L in the distal part of the dorsal subiculum and the entire ventral subiculum, labeled fibers were also present in clusters of histaminergic cells located around the mammillary nuclei. The density of the PHA-L labeled fibers within these clusters increased from low to moderate in association with a shift of the injection sites from dorsal to ventral and from proximal to distal parts of the subiculum, i.e., the highest fiber labeling was seen after injections of PHA-L in the distal part of the ventral subiculum. In the latter experiments, PHA-L labeled fibers reached HDC-immunoreactive neurons in the tuberal magnocellular nucleus, the deepest layer of the caudal magnocellular nucleus, the two bridges of histaminergic cells in the posterior hypothalamus, and the histaminergic neurons scattered in the supramammillary region. A few labeled fibers invaded the postmammillary caudal magnocellular nucleus. The presence of varicosities on the PHA-L labeled fibers in close proximity to the cell bodies and dendrites of the histaminergic neurons suggest the existence of synaptic contacts.", "contents": "Subicular efferents to histaminergic neurons in the posterior hypothalamic region of the rat studied with PHA-L tracing combined with histidine decarboxylase immunocytochemistry. The projections from the subiculum to histaminergic cells in the posterior hypothalamic region of the rat were studied by means of anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin (PHA-L) combined with histidine decarboxylase (HDC)-immunohistochemistry. PHA-L was injected at various loci along the dorsoventral and proximodistal axes of the subiculum. This resulted in labeling of the fornix and of terminal plexuses at various locations in the diencephalon and the mammillary body. Following deposition of PHA-L in the proximal part of the dorsal subiculum, labeled fibers in the posterior hypothalamus were confined to the mammillary nuclei, whereas after injections of PHA-L in the distal part of the dorsal subiculum and the entire ventral subiculum, labeled fibers were also present in clusters of histaminergic cells located around the mammillary nuclei. The density of the PHA-L labeled fibers within these clusters increased from low to moderate in association with a shift of the injection sites from dorsal to ventral and from proximal to distal parts of the subiculum, i.e., the highest fiber labeling was seen after injections of PHA-L in the distal part of the ventral subiculum. In the latter experiments, PHA-L labeled fibers reached HDC-immunoreactive neurons in the tuberal magnocellular nucleus, the deepest layer of the caudal magnocellular nucleus, the two bridges of histaminergic cells in the posterior hypothalamus, and the histaminergic neurons scattered in the supramammillary region. A few labeled fibers invaded the postmammillary caudal magnocellular nucleus. The presence of varicosities on the PHA-L labeled fibers in close proximity to the cell bodies and dendrites of the histaminergic neurons suggest the existence of synaptic contacts."} {"id": "PMID:1282533", "title": "Lipopolysaccharide heterogeneity in Pasteurella haemolytica isolates from cattle and sheep.", "content": "Lipopolysaccharide (LPS) from 40 isolates of Pasteurella haemolytica, comprising 23 serotype A1, seven serotype A2, one serotype T4, one serotype T10 and eight untypable isolates, obtained from diseased and healthy cattle or sheep, was characterized by SDS-PAGE and Western blotting. Ten different SDS-PAGE LPS profiles, five smooth and five rough, were identified among the biotype A and untypable isolates and designated LPS types 1-10. LPS types 1 and 2 were smooth, had similar O-antigen banding-patterns but differed in the low-molecular-mass or core-oligosaccharide regions; type 3 LPS was rough but had a core-oligosaccharide region similar to that of LPS type 1. No similarities were observed between these LPS types and types 6, 7 and 9, which were smooth, and types 4, 5, 8 and 10, which were rough. Most serotype A1 isolates (19/23) were of LPS type 1, whereas two isolates each had LPS of types 2 and 3. The majority (5/7) of serotype A2 isolates possessed type 3 LPS, whereas the remaining two isolates each had LPS of types 4 and 5. There was much greater heterogeneity within the untypable group of isolates, which comprised LPS of types 1 and 9 (two isolates each), and 6, 7, 8 or 10 (one isolate each). Western blotting analysis demonstrated that LPS types 1 and 2 had immunologically identical O-antigen side-chains but differed in their core-oligosaccharide regions, whereas the core-oligosaccharide region of rough LPS type 3 was immunologically very similar to that of LPS type 1. The other LPS types were immunologically unrelated to these three LPS types. The majority (20/23) of serotype A1 isolates originated from cattle and possessed LPS types 1 or 2, different from most (5/7) of the serotype A2 isolates which originated from sheep and possessed LPS of types 3 or 4. However, two of the three ovine serotype A1 isolates had the same type 3 LPS as occurred in most of the ovine serotype A2 isolates, suggesting a possible correlation between LPS type and host specificity. This study has demonstrated that LPS diversity within different serotypes of P. haemolytica is greater than was previously thought and that certain LPS types might be host-specific.", "contents": "Lipopolysaccharide heterogeneity in Pasteurella haemolytica isolates from cattle and sheep. Lipopolysaccharide (LPS) from 40 isolates of Pasteurella haemolytica, comprising 23 serotype A1, seven serotype A2, one serotype T4, one serotype T10 and eight untypable isolates, obtained from diseased and healthy cattle or sheep, was characterized by SDS-PAGE and Western blotting. Ten different SDS-PAGE LPS profiles, five smooth and five rough, were identified among the biotype A and untypable isolates and designated LPS types 1-10. LPS types 1 and 2 were smooth, had similar O-antigen banding-patterns but differed in the low-molecular-mass or core-oligosaccharide regions; type 3 LPS was rough but had a core-oligosaccharide region similar to that of LPS type 1. No similarities were observed between these LPS types and types 6, 7 and 9, which were smooth, and types 4, 5, 8 and 10, which were rough. Most serotype A1 isolates (19/23) were of LPS type 1, whereas two isolates each had LPS of types 2 and 3. The majority (5/7) of serotype A2 isolates possessed type 3 LPS, whereas the remaining two isolates each had LPS of types 4 and 5. There was much greater heterogeneity within the untypable group of isolates, which comprised LPS of types 1 and 9 (two isolates each), and 6, 7, 8 or 10 (one isolate each). Western blotting analysis demonstrated that LPS types 1 and 2 had immunologically identical O-antigen side-chains but differed in their core-oligosaccharide regions, whereas the core-oligosaccharide region of rough LPS type 3 was immunologically very similar to that of LPS type 1. The other LPS types were immunologically unrelated to these three LPS types. The majority (20/23) of serotype A1 isolates originated from cattle and possessed LPS types 1 or 2, different from most (5/7) of the serotype A2 isolates which originated from sheep and possessed LPS of types 3 or 4. However, two of the three ovine serotype A1 isolates had the same type 3 LPS as occurred in most of the ovine serotype A2 isolates, suggesting a possible correlation between LPS type and host specificity. This study has demonstrated that LPS diversity within different serotypes of P. haemolytica is greater than was previously thought and that certain LPS types might be host-specific."} {"id": "PMID:1282534", "title": "Targeting of specific domains of diphtheria toxin by site-directed antibodies.", "content": "Antibodies highly selective for two functionally distinct regions of diphtheria toxin (DTx) were prepared using synthetic peptide conjugates as immunogens. Three peptides were selected for synthesis: sequence DTx141-157 on fragment A, which contains the putative protein elongation factor (EF-2) ADP-ribosyltransferase site; DTx224-237 on fragment B, selected on the basis of forming a predicted surface loop; and DTx513-526 on fragment B, forming a part of the region containing the putative receptor binding domain. All of the anti-peptide antibodies recognized the corresponding peptide, and also reacted with the toxin, specifically with the fragment containing the sequence against which they were raised, confirming the utility of this approach in generating fragment-specific antibodies. The anti-peptide antibody with the highest binding titre both to the peptide and to the native toxin was the one prepared against the sequence with the highest surface and loop likelihood indices of the three peptides selected. The similarity of the reactivity profiles with peptide and native and denatured toxin is consistent with the prediction that the region selected occurs in a surface loop and that the structure of the peptide is similar to the conformation of this region in the native protein. The epitopes for two of the anti-peptide antibodies were mapped. The results indicated that even though the antisera were raised to peptides containing 14 amino acids (aa) they were directed predominantly against a narrow region within the peptide, consisting of only 5-6 aa residues.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Targeting of specific domains of diphtheria toxin by site-directed antibodies. Antibodies highly selective for two functionally distinct regions of diphtheria toxin (DTx) were prepared using synthetic peptide conjugates as immunogens. Three peptides were selected for synthesis: sequence DTx141-157 on fragment A, which contains the putative protein elongation factor (EF-2) ADP-ribosyltransferase site; DTx224-237 on fragment B, selected on the basis of forming a predicted surface loop; and DTx513-526 on fragment B, forming a part of the region containing the putative receptor binding domain. All of the anti-peptide antibodies recognized the corresponding peptide, and also reacted with the toxin, specifically with the fragment containing the sequence against which they were raised, confirming the utility of this approach in generating fragment-specific antibodies. The anti-peptide antibody with the highest binding titre both to the peptide and to the native toxin was the one prepared against the sequence with the highest surface and loop likelihood indices of the three peptides selected. The similarity of the reactivity profiles with peptide and native and denatured toxin is consistent with the prediction that the region selected occurs in a surface loop and that the structure of the peptide is similar to the conformation of this region in the native protein. The epitopes for two of the anti-peptide antibodies were mapped. The results indicated that even though the antisera were raised to peptides containing 14 amino acids (aa) they were directed predominantly against a narrow region within the peptide, consisting of only 5-6 aa residues.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282535", "title": "Antibodies recognizing a variety of different structural motifs on meningococcal Lip antigen fail to demonstrate bactericidal activity.", "content": "The neisserial Lip antigen is a conserved antigen associated with the pathogenic Neisseria species, and is composed of multiple repeats of a consensus pentapeptide. A series of monoclonal antibodies reacting with meningococcal Lip antigen were subjected to epitope mapping, using solid-phase synthetic peptides based on the consensus repeat sequence. The antibodies were found to recognize different continuous epitopes based on the consensus sequence. One monoclonal antibody was utilized in affinity chromatography to obtain purified Lip antigen and the antigen was used for immunization of mice. The resulting antisera did not recognize Lip antigen on Western blots but reacted specifically with Lip antigen in immune precipitation experiments, indicating that the predominant polyclonal immune response was directed against conformational epitopes. Despite the diversity of both continuous and conformational epitopes recognized by the antibodies produced, none of the antibodies demonstrated the ability to promote complement-mediated bactericidal activity. Thus despite its initial apparent promise as a potential vaccine candidate the case for the inclusion of Lip antigen in vaccine formulation cannot be supported at present.", "contents": "Antibodies recognizing a variety of different structural motifs on meningococcal Lip antigen fail to demonstrate bactericidal activity. The neisserial Lip antigen is a conserved antigen associated with the pathogenic Neisseria species, and is composed of multiple repeats of a consensus pentapeptide. A series of monoclonal antibodies reacting with meningococcal Lip antigen were subjected to epitope mapping, using solid-phase synthetic peptides based on the consensus repeat sequence. The antibodies were found to recognize different continuous epitopes based on the consensus sequence. One monoclonal antibody was utilized in affinity chromatography to obtain purified Lip antigen and the antigen was used for immunization of mice. The resulting antisera did not recognize Lip antigen on Western blots but reacted specifically with Lip antigen in immune precipitation experiments, indicating that the predominant polyclonal immune response was directed against conformational epitopes. Despite the diversity of both continuous and conformational epitopes recognized by the antibodies produced, none of the antibodies demonstrated the ability to promote complement-mediated bactericidal activity. Thus despite its initial apparent promise as a potential vaccine candidate the case for the inclusion of Lip antigen in vaccine formulation cannot be supported at present."} {"id": "PMID:1282536", "title": "Isolation and characterization of adhesin-defective TnphoA mutants of septicaemic porcine Escherichia coli of serotype O115:K-:F165.", "content": "Non-enterotoxigenic porcine Escherichia coli strains belonging to the serogroup O115 have been associated with septicaemia and diarrhoea. Putative factors important in the pathogenicity of E. coli of serogroup O115 include fimbrial antigen F165, haemagglutination (MRHA), lipopolysaccharide, serum resistance, capsule and production of aerobactin. Using TnphoA transposon insertion mutagenesis, two classes of mutants were obtained from E. coli of serotype O115:F165 with respect to the phenotypic expression of fimbrial antigen F165 and MRHA of sheep erythrocytes: class I, F165-MRHA-, serum resistant; class II, F165+MRHA-, serum resistant. In a chicken lethality model, class I mutants were either virulent or of intermediate virulence, while class II mutants were of intermediate virulence. Alkaline phosphatase activity of class I and class II TnphoA mutants showed similar environmental regulation to that of fimbrial antigen F165. Moreover, class I and class II mutants were mutated in the prs-like locus, and lacked a 18.5 kDa and/or a 17.5 kDa fimbrial band.", "contents": "Isolation and characterization of adhesin-defective TnphoA mutants of septicaemic porcine Escherichia coli of serotype O115:K-:F165. Non-enterotoxigenic porcine Escherichia coli strains belonging to the serogroup O115 have been associated with septicaemia and diarrhoea. Putative factors important in the pathogenicity of E. coli of serogroup O115 include fimbrial antigen F165, haemagglutination (MRHA), lipopolysaccharide, serum resistance, capsule and production of aerobactin. Using TnphoA transposon insertion mutagenesis, two classes of mutants were obtained from E. coli of serotype O115:F165 with respect to the phenotypic expression of fimbrial antigen F165 and MRHA of sheep erythrocytes: class I, F165-MRHA-, serum resistant; class II, F165+MRHA-, serum resistant. In a chicken lethality model, class I mutants were either virulent or of intermediate virulence, while class II mutants were of intermediate virulence. Alkaline phosphatase activity of class I and class II TnphoA mutants showed similar environmental regulation to that of fimbrial antigen F165. Moreover, class I and class II mutants were mutated in the prs-like locus, and lacked a 18.5 kDa and/or a 17.5 kDa fimbrial band."} {"id": "PMID:1282537", "title": "Influence of prophylaxis on proximal venous thrombus formation after total hip arthroplasty.", "content": "Deep vein thrombosis (DVT) is the most frequent complication after total hip arthroplasty, and proximal DVT is more likely to produce clinical pulmonary emboli than distal DVT. The authors have assessed the incidence and anatomic location of phlebographically proven fresh DVT following total hip arthroplasty in 855 patients over 39 years of age. Eight different regimens (2 warfarin, 3 aspirin, 1 dextran, 1 external pneumatic compression, and 1 dextran combined with external pneumatic compression) were evaluated and compared with an historical placebo control group from the same institution. No significant difference (P < .05) existed in proximal DVT incidence between the placebo group and any of the three aspirin groups, the dextran group, the external pneumatic compression group, or the dextran combined with external pneumatic compression group. In contrast, warfarin, given both in traditional and low-dose regimens, provided a significant reduction in proximal DVT compared with the placebo group (P < .001; statistical power, 0.84 and 0.99, respectively). The low-dose regimen had 10 times fewer bleeding complications than the traditional regimen. All prophylaxis regimens should be evaluated for both proximal and distal DVT formation, as well as for overall incidence. Low-dose warfarin offers the best protection against proximal thrombi of the agents studied, and it is also safer than traditional dosages of warfarin.", "contents": "Influence of prophylaxis on proximal venous thrombus formation after total hip arthroplasty. Deep vein thrombosis (DVT) is the most frequent complication after total hip arthroplasty, and proximal DVT is more likely to produce clinical pulmonary emboli than distal DVT. The authors have assessed the incidence and anatomic location of phlebographically proven fresh DVT following total hip arthroplasty in 855 patients over 39 years of age. Eight different regimens (2 warfarin, 3 aspirin, 1 dextran, 1 external pneumatic compression, and 1 dextran combined with external pneumatic compression) were evaluated and compared with an historical placebo control group from the same institution. No significant difference (P < .05) existed in proximal DVT incidence between the placebo group and any of the three aspirin groups, the dextran group, the external pneumatic compression group, or the dextran combined with external pneumatic compression group. In contrast, warfarin, given both in traditional and low-dose regimens, provided a significant reduction in proximal DVT compared with the placebo group (P < .001; statistical power, 0.84 and 0.99, respectively). The low-dose regimen had 10 times fewer bleeding complications than the traditional regimen. All prophylaxis regimens should be evaluated for both proximal and distal DVT formation, as well as for overall incidence. Low-dose warfarin offers the best protection against proximal thrombi of the agents studied, and it is also safer than traditional dosages of warfarin."} {"id": "PMID:1282538", "title": "Potent inhibitors of histamine release, two novel triterpenoids from the Okinawan marine sponge Penares incrustans.", "content": "Two novel triterpenoids with an unusual 14-carboxyl group, penasterone [1] and acetylpenasterol [2], were isolated from the Okinawan marine sponge Penares incrustans. The structures of 1 and 2 were established mainly on the basis of nmr spectroscopic data. The relative stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis. Compounds 1 and 2 potently inhibited histamine release from rat peritoneal mast cells induced by anti-IgE in a dose-dependent manner.", "contents": "Potent inhibitors of histamine release, two novel triterpenoids from the Okinawan marine sponge Penares incrustans. Two novel triterpenoids with an unusual 14-carboxyl group, penasterone [1] and acetylpenasterol [2], were isolated from the Okinawan marine sponge Penares incrustans. The structures of 1 and 2 were established mainly on the basis of nmr spectroscopic data. The relative stereochemistry of 1 was confirmed by single-crystal X-ray diffraction analysis. Compounds 1 and 2 potently inhibited histamine release from rat peritoneal mast cells induced by anti-IgE in a dose-dependent manner."} {"id": "PMID:1282539", "title": "Neuroenteric cyst of the optic nerve: case report with immunohistochemical study.", "content": "A 36 year old man developed slowly progressive unilateral visual loss due to a cystic lesion of the intraorbital optic nerve. Pathologically the lesion was an epithelium lined cyst entirely within the atrophic nerve. The cyst lining consisted of columnar epithelium partly pseudostratified and ciliated with evidence of mucin secretion, and was immunoactive for cytokeratin but not glial fibrillary acidic protein. This lesion is considered to be similar to neuroenteric cysts that have been reported elsewhere in the nervous system, and the immunocytochemical results are consistent with a heterotopia derived from the primitive ectoderm of the stomatodeum.", "contents": "Neuroenteric cyst of the optic nerve: case report with immunohistochemical study. A 36 year old man developed slowly progressive unilateral visual loss due to a cystic lesion of the intraorbital optic nerve. Pathologically the lesion was an epithelium lined cyst entirely within the atrophic nerve. The cyst lining consisted of columnar epithelium partly pseudostratified and ciliated with evidence of mucin secretion, and was immunoactive for cytokeratin but not glial fibrillary acidic protein. This lesion is considered to be similar to neuroenteric cysts that have been reported elsewhere in the nervous system, and the immunocytochemical results are consistent with a heterotopia derived from the primitive ectoderm of the stomatodeum."} {"id": "PMID:1282540", "title": "Functional properties and axon terminations of interneurons in laminae III-V of the mammalian spinal dorsal horn in vitro.", "content": "1. The functional organization of interneurons in spinal laminae III-V was studied in an isolated preparation of hamster dorsal horn with sensory innervation from an excised skin patch. Morphological details of 40 neurons were visualized by intracellular injection of horseradish peroxidase. Active and passive membrane properties, synaptic responses to cutaneous nerve volleys, and responses to innocuous mechanical stimuli were determined for 25 cells with identified axons. 2. Neurons were classified into two types: 1) cells with local axons, branching in proximity to the cell soma and dendrites, that produced numerous synaptic boutons (740 +/- 504/axon; mean +/- SD), often arranged in clusters and 2) neurons with deep axons that usually bifurcated into rostral and caudal daughter branches up to 2.5 mm long, giving off collaterals ventral to the cell body and dendrites and forming significantly fewer boutons (155 +/- 140/axon) than local axon cells. A majority of boutons of local axon and deep axon cells, 89 and 83%, respectively, were of the en passant type. 3. Dendritic trees of local axon cells were relatively compact dorsoventrally (119 +/- 42 microns) and mediolaterally (128 +/- 45 microns), but were elongated rostrocaudally (404 +/- 121 microns). In comparison, dendritic trees of deep axon cells radiated significantly farther dorsoventrally (218 +/- 88 microns) and mediolaterally (180 +/- 34 microns), but exhibited comparable rostrocaudal spread (413 +/- 128 microns). There was no correlation between dorsoventral and mediolateral dendritic spread and mediolateral soma location for either cell type. However, for medially situated deep axon cells the rostrocaudal dendritic spread was up to 180% greater than for those located laterally. For nearly one-half of all cells (49%; 17/35) dendritic processes extended dorsally into lamina II. 4. Local axon cells had resting membrane potentials that were more negative than deep axon cells (-59.5 +/- 6.1 and -53.6 +/- 4.7 mV, respectively), but the amplitude and duration of action potentials generated by the two types were similar. Neuronal input resistance (RN) and membrane time constant (tau m) varied widely from cell to cell, but were not significantly different for local axon (77.4 +/- 46.8 M omega, 13.4 +/- 9.5 ms) and deep axon cells (46.5 +/- 19.2 M omega, 6.6 +/- 3.0 ms). 5. Volleys in myelinated afferent fibers activated fast rising excitatory postsynaptic potentials (EPSPs) that exhibited later, more slowly rising potentials with multiple components in a majority of deep axon (89%) and local axon (72%) neurons.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Functional properties and axon terminations of interneurons in laminae III-V of the mammalian spinal dorsal horn in vitro. 1. The functional organization of interneurons in spinal laminae III-V was studied in an isolated preparation of hamster dorsal horn with sensory innervation from an excised skin patch. Morphological details of 40 neurons were visualized by intracellular injection of horseradish peroxidase. Active and passive membrane properties, synaptic responses to cutaneous nerve volleys, and responses to innocuous mechanical stimuli were determined for 25 cells with identified axons. 2. Neurons were classified into two types: 1) cells with local axons, branching in proximity to the cell soma and dendrites, that produced numerous synaptic boutons (740 +/- 504/axon; mean +/- SD), often arranged in clusters and 2) neurons with deep axons that usually bifurcated into rostral and caudal daughter branches up to 2.5 mm long, giving off collaterals ventral to the cell body and dendrites and forming significantly fewer boutons (155 +/- 140/axon) than local axon cells. A majority of boutons of local axon and deep axon cells, 89 and 83%, respectively, were of the en passant type. 3. Dendritic trees of local axon cells were relatively compact dorsoventrally (119 +/- 42 microns) and mediolaterally (128 +/- 45 microns), but were elongated rostrocaudally (404 +/- 121 microns). In comparison, dendritic trees of deep axon cells radiated significantly farther dorsoventrally (218 +/- 88 microns) and mediolaterally (180 +/- 34 microns), but exhibited comparable rostrocaudal spread (413 +/- 128 microns). There was no correlation between dorsoventral and mediolateral dendritic spread and mediolateral soma location for either cell type. However, for medially situated deep axon cells the rostrocaudal dendritic spread was up to 180% greater than for those located laterally. For nearly one-half of all cells (49%; 17/35) dendritic processes extended dorsally into lamina II. 4. Local axon cells had resting membrane potentials that were more negative than deep axon cells (-59.5 +/- 6.1 and -53.6 +/- 4.7 mV, respectively), but the amplitude and duration of action potentials generated by the two types were similar. Neuronal input resistance (RN) and membrane time constant (tau m) varied widely from cell to cell, but were not significantly different for local axon (77.4 +/- 46.8 M omega, 13.4 +/- 9.5 ms) and deep axon cells (46.5 +/- 19.2 M omega, 6.6 +/- 3.0 ms). 5. Volleys in myelinated afferent fibers activated fast rising excitatory postsynaptic potentials (EPSPs) that exhibited later, more slowly rising potentials with multiple components in a majority of deep axon (89%) and local axon (72%) neurons.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282541", "title": "Expression of NMDA channels on cerebellar Purkinje cells acutely dissociated from newborn rats.", "content": "1. Conflicting evidence exists concerning the expression and properties of N-methyl-D-aspartate (NMDA) receptors on cerebellar Purkinje cells during development. We used whole-cell and single-channel recording to examine NMDA receptors on acutely dissociated Purkinje cells from newborn rats (postnatal day 0-4). 2. NMDA channels were present on > 80% of identified Purkinje cells and had pharmacological and single-channel properties that were indistinguishable from NMDA receptors on other neurons. In particular, responses were glycine-dependent and Mg2+ produced flickery open-channel block. 3. Our results demonstrate the transient expression of NMDA receptor/channels on Purkinje cells early in development. As NMDA receptors have been implicated in developmental plasticity in other regions of the CNS, a similar role is feasible during climbing fiber innervation of Purkinje cells.", "contents": "Expression of NMDA channels on cerebellar Purkinje cells acutely dissociated from newborn rats. 1. Conflicting evidence exists concerning the expression and properties of N-methyl-D-aspartate (NMDA) receptors on cerebellar Purkinje cells during development. We used whole-cell and single-channel recording to examine NMDA receptors on acutely dissociated Purkinje cells from newborn rats (postnatal day 0-4). 2. NMDA channels were present on > 80% of identified Purkinje cells and had pharmacological and single-channel properties that were indistinguishable from NMDA receptors on other neurons. In particular, responses were glycine-dependent and Mg2+ produced flickery open-channel block. 3. Our results demonstrate the transient expression of NMDA receptor/channels on Purkinje cells early in development. As NMDA receptors have been implicated in developmental plasticity in other regions of the CNS, a similar role is feasible during climbing fiber innervation of Purkinje cells."} {"id": "PMID:1282543", "title": "Sacrococcygeal teratoma in Sweden: a 10-year national retrospective study.", "content": "Thirty-two children with sacrococcygeal teratoma have been treated during the last 10 years (1980 to 1989) in Sweden. A retrospective study was performed in four departments of pediatric surgery that treat sacrococcygeal teratomas in children from the whole of Sweden. Prenatal and perinatal histories were reviewed together with interval to diagnosis, Altman classification, histology, and serum alpha-fetoprotein. Details of surgical management +/- adjuvant chemotherapy and outcome of patients were also documented. In 8 patients the teratoma was diagnosed prenatally by ultrasonography and there was one postoperative death in this group. Multiagent chemotherapy was used in all but one of 11 patients with malignant teratomas (in 8 of them a cisplatin, bleomycin, vinblastine combination). Only one patient with a malignant tumor treated by single-agent chemotherapy died, 8 others were still alive and tumor-free after 1 to 9 years (mean time, 5.4 years). Two patients developed late relapses and were treated by surgical resection. Metastases occurred in five of the 11 malignant tumors, one at presentation and in four patients 10 to 29 months following surgery. All relapses had distant metastases as well as local disease. Serum alpha-fetoprotein was used in monitoring some of these patients.", "contents": "Sacrococcygeal teratoma in Sweden: a 10-year national retrospective study. Thirty-two children with sacrococcygeal teratoma have been treated during the last 10 years (1980 to 1989) in Sweden. A retrospective study was performed in four departments of pediatric surgery that treat sacrococcygeal teratomas in children from the whole of Sweden. Prenatal and perinatal histories were reviewed together with interval to diagnosis, Altman classification, histology, and serum alpha-fetoprotein. Details of surgical management +/- adjuvant chemotherapy and outcome of patients were also documented. In 8 patients the teratoma was diagnosed prenatally by ultrasonography and there was one postoperative death in this group. Multiagent chemotherapy was used in all but one of 11 patients with malignant teratomas (in 8 of them a cisplatin, bleomycin, vinblastine combination). Only one patient with a malignant tumor treated by single-agent chemotherapy died, 8 others were still alive and tumor-free after 1 to 9 years (mean time, 5.4 years). Two patients developed late relapses and were treated by surgical resection. Metastases occurred in five of the 11 malignant tumors, one at presentation and in four patients 10 to 29 months following surgery. All relapses had distant metastases as well as local disease. Serum alpha-fetoprotein was used in monitoring some of these patients."} {"id": "PMID:1282546", "title": "Median sternotomy wound dehiscence: a retrospective case control study of risk factors and outcome.", "content": "Over a 5-year period from 1985 to 1989, 2760 patients underwent open heart surgery at the University Hospital of Wales. Of these, 44 (1.6%, 35 men, mean age 61 years) developed median sternotomy dehiscence 2-40 (median 9) days after surgery. Infection was an associated factor in 18 patients (41%) and Staphylococcus aureus the predominant isolate in seven of those. Thirty-seven patients underwent rewiring of the sternotomy wound and seven patients underwent debridement, removal of wires and delayed closure. In those undergoing rewiring, sternal stability was maintained in 34 patients (92%). There were seven deaths (16%), of which two were considered to be wound-related. Median hospital stay of survivors was 34 (range 16-84) days. Comparison with 88 matched controls by univariate analysis showed preoperative chronic obstructive airways disease, reduced FEV1/FVC ratio (both P < 0.001) and smoking (P < 0.05) were all more common in the dehiscence group. In addition, reoperation for bleeding (P < 0.05), prolonged bypass time, postoperative ventilation period and length of stay in the intensive care unit (all P < 0.001) were more common in the study group.", "contents": "Median sternotomy wound dehiscence: a retrospective case control study of risk factors and outcome. Over a 5-year period from 1985 to 1989, 2760 patients underwent open heart surgery at the University Hospital of Wales. Of these, 44 (1.6%, 35 men, mean age 61 years) developed median sternotomy dehiscence 2-40 (median 9) days after surgery. Infection was an associated factor in 18 patients (41%) and Staphylococcus aureus the predominant isolate in seven of those. Thirty-seven patients underwent rewiring of the sternotomy wound and seven patients underwent debridement, removal of wires and delayed closure. In those undergoing rewiring, sternal stability was maintained in 34 patients (92%). There were seven deaths (16%), of which two were considered to be wound-related. Median hospital stay of survivors was 34 (range 16-84) days. Comparison with 88 matched controls by univariate analysis showed preoperative chronic obstructive airways disease, reduced FEV1/FVC ratio (both P < 0.001) and smoking (P < 0.05) were all more common in the dehiscence group. In addition, reoperation for bleeding (P < 0.05), prolonged bypass time, postoperative ventilation period and length of stay in the intensive care unit (all P < 0.001) were more common in the study group."} {"id": "PMID:1282547", "title": "'Fracture' of the penis in Enugu, Nigeria.", "content": "Eight cases of 'fracture' of the penis in a Negro population over a 5-year period are presented. The majority of the cases occurred on the right side in association with sexual activity. All gave a positive history of sexually transmitted disease. We recommend prompt operative treatment that is aimed at full functional and cosmetic recovery.", "contents": "'Fracture' of the penis in Enugu, Nigeria. Eight cases of 'fracture' of the penis in a Negro population over a 5-year period are presented. The majority of the cases occurred on the right side in association with sexual activity. All gave a positive history of sexually transmitted disease. We recommend prompt operative treatment that is aimed at full functional and cosmetic recovery."} {"id": "PMID:1282548", "title": "Transcranial Doppler measurement before and after carotid endarterectomy.", "content": "Carotid endarterectomy not only removes a source of emboli but significantly increases flow up the internal carotid artery (ICA). ICA flow and middle cerebral artery velocity (Vmca) measurements were made before, during and after endarterectomy in 40 consecutive patients. Mean ICA flow increased from 207 ml/min (95% confidence interval (CI) 136-259) to 388 ml/min (95% CI 348-428) (P < 0.001, Mann-Whitney U test) following endarterectomy. Despite this, Vmca did not rise significantly at the end of the procedure. By the first postoperative day Vmca rose to 55.3 cm/s (95% CI 47.6-62.4) (P < 0.025, ANOVA) only to fall preoperative values (46.0 cm/s (95% CI 40.0-52.1)) by 6 weeks. These results suggest that cerebral autoregulation takes time to adapt to the increased flow and pressure following endarterectomy, but has stabilized by 6 weeks.", "contents": "Transcranial Doppler measurement before and after carotid endarterectomy. Carotid endarterectomy not only removes a source of emboli but significantly increases flow up the internal carotid artery (ICA). ICA flow and middle cerebral artery velocity (Vmca) measurements were made before, during and after endarterectomy in 40 consecutive patients. Mean ICA flow increased from 207 ml/min (95% confidence interval (CI) 136-259) to 388 ml/min (95% CI 348-428) (P < 0.001, Mann-Whitney U test) following endarterectomy. Despite this, Vmca did not rise significantly at the end of the procedure. By the first postoperative day Vmca rose to 55.3 cm/s (95% CI 47.6-62.4) (P < 0.025, ANOVA) only to fall preoperative values (46.0 cm/s (95% CI 40.0-52.1)) by 6 weeks. These results suggest that cerebral autoregulation takes time to adapt to the increased flow and pressure following endarterectomy, but has stabilized by 6 weeks."} {"id": "PMID:1282549", "title": "Neopylorus: a functional reflux-free gastroenteral anastomosis.", "content": "To minimize the loss of pyloric function associated with partial gastrectomy (PG), a functional surrogate pylorus, or neopylorus, was made by means of a pantaloon jejunoplastic pouch into which the gastrojejunal stoma was invaginated. This report concerns a consecutive series of 84 patients who underwent PG according to currently accepted criteria. The results showed that formation of the neopylorus apparently prevents dumping and may avoid the necessity for vagotomy in cases without serious hypersecretion. PG patients with a neopylorus formed over 13 years ago still exhibit no enterogastric reflux, gastritis, anaemia, steatorrhoea or sequelae of impaired digestion. Patient satisfaction has been most encouraging. Because this report is a feasibility trial only, no statistical analysis is presented.", "contents": "Neopylorus: a functional reflux-free gastroenteral anastomosis. To minimize the loss of pyloric function associated with partial gastrectomy (PG), a functional surrogate pylorus, or neopylorus, was made by means of a pantaloon jejunoplastic pouch into which the gastrojejunal stoma was invaginated. This report concerns a consecutive series of 84 patients who underwent PG according to currently accepted criteria. The results showed that formation of the neopylorus apparently prevents dumping and may avoid the necessity for vagotomy in cases without serious hypersecretion. PG patients with a neopylorus formed over 13 years ago still exhibit no enterogastric reflux, gastritis, anaemia, steatorrhoea or sequelae of impaired digestion. Patient satisfaction has been most encouraging. Because this report is a feasibility trial only, no statistical analysis is presented."} {"id": "PMID:1282550", "title": "Investigation of cervical lymphadenopathy presumed to be metastatic in nature: a review of current clinical practice.", "content": "The method adopted by UK otolaryngologists for investigating cervical lymphadenopathy presumed to be metastatic in nature is reported. This is based on a confidential questionnaire sent to all members of the British Association of Otolaryngologists. The results of this survey show that the majority of otolaryngologists make a diligent search for a possible primary tumour by performing a panendoscopy. They do not, however, make full use of other investigative techniques such as fine needle aspiration cytology (9%) or computed tomography (6%). The management of patients with cervical masses could be improved by more widespread use of computed tomographic scanning where available and the development of fine needle aspiration cytology in all departments performing head and neck surgery.", "contents": "Investigation of cervical lymphadenopathy presumed to be metastatic in nature: a review of current clinical practice. The method adopted by UK otolaryngologists for investigating cervical lymphadenopathy presumed to be metastatic in nature is reported. This is based on a confidential questionnaire sent to all members of the British Association of Otolaryngologists. The results of this survey show that the majority of otolaryngologists make a diligent search for a possible primary tumour by performing a panendoscopy. They do not, however, make full use of other investigative techniques such as fine needle aspiration cytology (9%) or computed tomography (6%). The management of patients with cervical masses could be improved by more widespread use of computed tomographic scanning where available and the development of fine needle aspiration cytology in all departments performing head and neck surgery."} {"id": "PMID:1282551", "title": "Mondor's disease: analysis of 30 cases.", "content": "Thrombophlebitis of the superficial veins of the breast is a well known disease entity, the aetiology of which remains obscure. It affects mostly middle-aged women with large pendulous breasts. The present study suggests that the causative agent may not be a single factor but rather a combination of factors. Thirty cases (28 women, two men) are presented and analysed. A larger multicentre study is recommended.", "contents": "Mondor's disease: analysis of 30 cases. Thrombophlebitis of the superficial veins of the breast is a well known disease entity, the aetiology of which remains obscure. It affects mostly middle-aged women with large pendulous breasts. The present study suggests that the causative agent may not be a single factor but rather a combination of factors. Thirty cases (28 women, two men) are presented and analysed. A larger multicentre study is recommended."} {"id": "PMID:1282552", "title": "Value of scintigraphic localization of obscure gastrointestinal bleeding.", "content": "A total of 51 technetium-99m (99mTc)-labelled autologous red cell (LRC) scans performed on 49 patients for the localization of obscure gastrointestinal bleeding over a 5-year period was reviewed. The sensitivity for LRC scanning was 72.7% with a positive predictive value of 84.2%. Forty patients underwent both LRC scanning and visceral angiography during the same admission; angiography had a sensitivity of 38.9% compared with 66.7% for LRC scanning and the positive predictive values were 77.8% and 85.7%, respectively. Overall, the site of bleeding was located in 22 (45%) of 49 patients, but LRC scanning alone was successful in identifying the lesion in 16 (33%) cases. In patients who continue to bleed to the point of requiring operation, a combination of scintigraphy and angiography will localize a source in 70% of patients.", "contents": "Value of scintigraphic localization of obscure gastrointestinal bleeding. A total of 51 technetium-99m (99mTc)-labelled autologous red cell (LRC) scans performed on 49 patients for the localization of obscure gastrointestinal bleeding over a 5-year period was reviewed. The sensitivity for LRC scanning was 72.7% with a positive predictive value of 84.2%. Forty patients underwent both LRC scanning and visceral angiography during the same admission; angiography had a sensitivity of 38.9% compared with 66.7% for LRC scanning and the positive predictive values were 77.8% and 85.7%, respectively. Overall, the site of bleeding was located in 22 (45%) of 49 patients, but LRC scanning alone was successful in identifying the lesion in 16 (33%) cases. In patients who continue to bleed to the point of requiring operation, a combination of scintigraphy and angiography will localize a source in 70% of patients."} {"id": "PMID:1282553", "title": "Acute epiglottitis in adults: a potentially lethal cause of sore throat.", "content": "The diagnosis, management and outcome in 12 adults with acute epiglottitis was reviewed. Painful dysphagia was a universal symptom and respiratory distress affected eight patients, six of whom required urgent airway intervention. All patients received parenteral antibiotics, ten received steroids and four received adrenaline. Respiratory distress resolved in two patients given adrenaline and airway intervention was avoided. Indirect laryngoscopy is the investigation of choice and this is preferable to neck radiology. Two patients died and it is stressed that this condition must be distinguished from other more common causes of a severe sore throat. The patient should be managed in a unit with the facilities and expertise to effect acute airway intervention.", "contents": "Acute epiglottitis in adults: a potentially lethal cause of sore throat. The diagnosis, management and outcome in 12 adults with acute epiglottitis was reviewed. Painful dysphagia was a universal symptom and respiratory distress affected eight patients, six of whom required urgent airway intervention. All patients received parenteral antibiotics, ten received steroids and four received adrenaline. Respiratory distress resolved in two patients given adrenaline and airway intervention was avoided. Indirect laryngoscopy is the investigation of choice and this is preferable to neck radiology. Two patients died and it is stressed that this condition must be distinguished from other more common causes of a severe sore throat. The patient should be managed in a unit with the facilities and expertise to effect acute airway intervention."} {"id": "PMID:1282557", "title": "Surgical treatment of adult trigger finger under local anaesthetic: the method of choice?", "content": "A prospective trial releasing 25 adult trigger fingers under a local anesthetic (5 ml 1% lignocaine with 1500 units hyalase) and a tourniquet was undertaken. All patients had excellent results and there was no complication. The adequacy of the release could be checked on the table by asking the patient to make a first actively, and any further measures necessary were carried out at the same time. It is recommended that the release of trigger fingers be carried out by this technique to minimize failures, as coexisting pathology causing two-level triggering can be identified and treated at the same time. The potential of complications is far less than with a general anaesthetic or a regional anaesthetic.", "contents": "Surgical treatment of adult trigger finger under local anaesthetic: the method of choice? A prospective trial releasing 25 adult trigger fingers under a local anesthetic (5 ml 1% lignocaine with 1500 units hyalase) and a tourniquet was undertaken. All patients had excellent results and there was no complication. The adequacy of the release could be checked on the table by asking the patient to make a first actively, and any further measures necessary were carried out at the same time. It is recommended that the release of trigger fingers be carried out by this technique to minimize failures, as coexisting pathology causing two-level triggering can be identified and treated at the same time. The potential of complications is far less than with a general anaesthetic or a regional anaesthetic."} {"id": "PMID:1282569", "title": "Potential anti-AIDS naphthalenesulfonic acid derivatives. Synthesis and inhibition of HIV-1 induced cytopathogenesis and HIV-1 and HIV-2 reverse transcriptase activities.", "content": "Several naphthalenedi- and trisulfonic acids have been synthesized and evaluated for inhibitory potential against cytopathogenesis and purified recombinant human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptase (RT). The most potent derivative that emerged from the anti-RT study was a small molecule 6 (MW = 840), a dipalmitoylated derivative of 2,7-naphthalenedisulfonic acid. Analog 6 demonstrated 50% inhibitory concentration (IC50) values of 2.42 and 0.86 microM for HIV-1 and HIV-2 RT, respectively. The second most active compound was also a derivative of the same naphthalenedisulfonic acid but contained only one palmitoyl moiety. This compound 9 displayed IC50 values of 4.8 and 3.7 microM for HIV-1 and HIV-2 RT, respectively. Both analogs 6 and 9 are active at noncytotoxic doses, exhibit slightly higher potencies for the RT of HIV-2 over HIV-1, and demonstrate activities superior to the hexasulfonic acid derivative suramin (IC50 values of 9.4 and 15.5 microM for HIV-1 and HIV-2 RT, respectively). In the cytopathogenesis assay, the most active compound is a bis naphthalenedisulfonic acid derivative 17, containing a flexible octamethylene spacer and exhibiting an in vitro therapeutic index of 29.7. Most striking, however, is the influence of the palmitoyl functionality in the naphthalenedisulfonic acid series to confer activity against both HIV-1 and HIV-2 RT.", "contents": "Potential anti-AIDS naphthalenesulfonic acid derivatives. Synthesis and inhibition of HIV-1 induced cytopathogenesis and HIV-1 and HIV-2 reverse transcriptase activities. Several naphthalenedi- and trisulfonic acids have been synthesized and evaluated for inhibitory potential against cytopathogenesis and purified recombinant human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptase (RT). The most potent derivative that emerged from the anti-RT study was a small molecule 6 (MW = 840), a dipalmitoylated derivative of 2,7-naphthalenedisulfonic acid. Analog 6 demonstrated 50% inhibitory concentration (IC50) values of 2.42 and 0.86 microM for HIV-1 and HIV-2 RT, respectively. The second most active compound was also a derivative of the same naphthalenedisulfonic acid but contained only one palmitoyl moiety. This compound 9 displayed IC50 values of 4.8 and 3.7 microM for HIV-1 and HIV-2 RT, respectively. Both analogs 6 and 9 are active at noncytotoxic doses, exhibit slightly higher potencies for the RT of HIV-2 over HIV-1, and demonstrate activities superior to the hexasulfonic acid derivative suramin (IC50 values of 9.4 and 15.5 microM for HIV-1 and HIV-2 RT, respectively). In the cytopathogenesis assay, the most active compound is a bis naphthalenedisulfonic acid derivative 17, containing a flexible octamethylene spacer and exhibiting an in vitro therapeutic index of 29.7. Most striking, however, is the influence of the palmitoyl functionality in the naphthalenedisulfonic acid series to confer activity against both HIV-1 and HIV-2 RT."} {"id": "PMID:1282571", "title": "Species differences in ciprofibrate induction of hepatic cytochrome P450 4A1 and peroxisome proliferation.", "content": "Six species (CD-1 mouse, Fischer 344 rat, Syrian golden hamster, Duncan-Hartley guinea pig, half-lop rabbit and marmoset monkey) were treated orally with ciprofibrate, a potent oxyisobutyrate hypolipidaemic drug for 14 days. A dose-dependent liver enlargment was observed in the mouse and rat and at the high dose level in the hamster. A marked dose-dependent increase in the 12-hydroxylation of lauric acid was observed in the treated mouse, hamster, rat, and rabbit, associated with a concomitant elevation in the specific content of cytochrome P-450 4A1 apoprotein, determined by an ELISA technique. Similarly, in these responsive species, an increase in mRNA levels coding for cytochrome P450 4A1 was observed. Lauric acid 12-hydroxylation was unchanged in the guinea pig and marmoset after ciprofibrate pretreatment, and cytochrome P-450 4A1 was not detected immunochemically in liver microsomes from these latter species. In the untreated mouse, hamster, rat, and rabbit, the 12-hydroxylation of lauric acid was more extensive than the 11-hydroxylation, whereas in the guinea pig and marmoset the activity ratios were reversed, with 11-hydroxylation predominating. Peroxisomal fatty acid beta-oxidation was markedly induced in the mouse, hamster, rat, and rabbit on treatment at the higher dose level (39-, 3-, 13- and 5-fold, respectively) and was slightly increased in the marmoset (2-fold), yet was unchanged in the guinea pig following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Species differences in ciprofibrate induction of hepatic cytochrome P450 4A1 and peroxisome proliferation. Six species (CD-1 mouse, Fischer 344 rat, Syrian golden hamster, Duncan-Hartley guinea pig, half-lop rabbit and marmoset monkey) were treated orally with ciprofibrate, a potent oxyisobutyrate hypolipidaemic drug for 14 days. A dose-dependent liver enlargment was observed in the mouse and rat and at the high dose level in the hamster. A marked dose-dependent increase in the 12-hydroxylation of lauric acid was observed in the treated mouse, hamster, rat, and rabbit, associated with a concomitant elevation in the specific content of cytochrome P-450 4A1 apoprotein, determined by an ELISA technique. Similarly, in these responsive species, an increase in mRNA levels coding for cytochrome P450 4A1 was observed. Lauric acid 12-hydroxylation was unchanged in the guinea pig and marmoset after ciprofibrate pretreatment, and cytochrome P-450 4A1 was not detected immunochemically in liver microsomes from these latter species. In the untreated mouse, hamster, rat, and rabbit, the 12-hydroxylation of lauric acid was more extensive than the 11-hydroxylation, whereas in the guinea pig and marmoset the activity ratios were reversed, with 11-hydroxylation predominating. Peroxisomal fatty acid beta-oxidation was markedly induced in the mouse, hamster, rat, and rabbit on treatment at the higher dose level (39-, 3-, 13- and 5-fold, respectively) and was slightly increased in the marmoset (2-fold), yet was unchanged in the guinea pig following treatment.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282572", "title": "[Clinical significance of recombinant human granulocyte colony-stimulating factor (rG-CSF) in the chemotherapy of patients with malignant lymphoma].", "content": "We examined the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on neutropenia induced by chemotherapy in 10 patients with non-Hodgkin's lymphoma (NHL). The numbers of peripheral blood hematopoietic progenitors were also evaluated before and after administration of rG-CSF. Six patients received an administration of 2 micrograms/kg/body weight of rG-CSF subcutaneously for 14 days after 2nd chemotherapy. Four patients received intravenous infusion of rG-CSF (300 micrograms/body/day) for 4 days from nadir state after chemotherapy. Administration of rG-CSF from the termination of chemotherapy, markedly shortend the period of bone marrow hypoplasia induced by chemotherapy. On the other hand, administration of rhG-CSF from nadir state after chemotherapy have accelerated the recovery of neutrophil counts. In addition, this type of therapy induced 26 to 60 folds increase of peripheral blood hematopoietic progenitors. These results demonstrate the validity of administration of rhG-CSF not only in the chemotherapy of NHL, but also in peripheral blood stem cell transplantation (PBSCT).", "contents": "[Clinical significance of recombinant human granulocyte colony-stimulating factor (rG-CSF) in the chemotherapy of patients with malignant lymphoma]. We examined the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on neutropenia induced by chemotherapy in 10 patients with non-Hodgkin's lymphoma (NHL). The numbers of peripheral blood hematopoietic progenitors were also evaluated before and after administration of rG-CSF. Six patients received an administration of 2 micrograms/kg/body weight of rG-CSF subcutaneously for 14 days after 2nd chemotherapy. Four patients received intravenous infusion of rG-CSF (300 micrograms/body/day) for 4 days from nadir state after chemotherapy. Administration of rG-CSF from the termination of chemotherapy, markedly shortend the period of bone marrow hypoplasia induced by chemotherapy. On the other hand, administration of rhG-CSF from nadir state after chemotherapy have accelerated the recovery of neutrophil counts. In addition, this type of therapy induced 26 to 60 folds increase of peripheral blood hematopoietic progenitors. These results demonstrate the validity of administration of rhG-CSF not only in the chemotherapy of NHL, but also in peripheral blood stem cell transplantation (PBSCT)."} {"id": "PMID:1282573", "title": "[Recombinant human granulocyte-colony stimulating factor (rhG-CSF) treatment for spleen abscess and periostitis in a patient with chronic granulomatous disease].", "content": "A 9-year-old boy with chronic granulomatous disease was hospitalized on May, 1991, because of continued fever and pain in the right elbow. Increased bone intensity at the distal end of right humerus on x-ray and a 33 x 36 mm space-occupying lesion in the spleen on abdominal CT scan were recognized. Under a diagnosis of periosteitis and spleen abscess, intravenous infusion of rhG-CSF at a dose of 200 micrograms/m2/day was started in combination with antimicrobial therapy. Fever, tenderness, swelling in the right elbow and inflammatory indices improved three weeks after the institution of therapy. Hydrogen peroxide (H2O2) formation by neutrophil increased significantly, although intermittently, during the therapy. The spleen abscess had completely vanished on CT scan on February, 1992. The therapy was well tolerated and no significant side effects were observed. The use of rhG-CSF in combination with potent antibiotics is recommended for patients with serious infections in chronic granulomatous disease to avoid a fatal course.", "contents": "[Recombinant human granulocyte-colony stimulating factor (rhG-CSF) treatment for spleen abscess and periostitis in a patient with chronic granulomatous disease]. A 9-year-old boy with chronic granulomatous disease was hospitalized on May, 1991, because of continued fever and pain in the right elbow. Increased bone intensity at the distal end of right humerus on x-ray and a 33 x 36 mm space-occupying lesion in the spleen on abdominal CT scan were recognized. Under a diagnosis of periosteitis and spleen abscess, intravenous infusion of rhG-CSF at a dose of 200 micrograms/m2/day was started in combination with antimicrobial therapy. Fever, tenderness, swelling in the right elbow and inflammatory indices improved three weeks after the institution of therapy. Hydrogen peroxide (H2O2) formation by neutrophil increased significantly, although intermittently, during the therapy. The spleen abscess had completely vanished on CT scan on February, 1992. The therapy was well tolerated and no significant side effects were observed. The use of rhG-CSF in combination with potent antibiotics is recommended for patients with serious infections in chronic granulomatous disease to avoid a fatal course."} {"id": "PMID:1282574", "title": "[Analysis of mononuclear cells in urine using flow cytometry: a useful tool for monitoring disease activity of proliferative glomerulonephritis].", "content": "We investigated CD56+ cells (natural killer cells), CD14+ cells (macrophage) and CD3+ cells (pan T cells) in urine using flow cytometry in various renal diseases including idiopathic crescentic glomerulonephritis, IgA nephropathy, membranoproliferative glomerulonephritis membranous nephropathy, pyelonephritis and idiopathic renal hematuria. A remarkable increase of CD56 cells in urine was observed in glomerulonephritis with marked necrotizing/and or crescentic (NC) lesions. The ratio of CD56+ cells/CD3+ cells was correlated with the severity of NC lesions. The ratio of CD14+ cells/CD3+ cells was increased in glomerulonephritis with endocapillary proliferation. Using immunohistochemical methods, CD56+ cells were also observed to be present in cellular crescents in biopsy specimens. These observations suggest that an analysis of these cells in urine using flow cytometry may be a useful tool for monitoring disease activity in proliferative glomerulonephritis.", "contents": "[Analysis of mononuclear cells in urine using flow cytometry: a useful tool for monitoring disease activity of proliferative glomerulonephritis]. We investigated CD56+ cells (natural killer cells), CD14+ cells (macrophage) and CD3+ cells (pan T cells) in urine using flow cytometry in various renal diseases including idiopathic crescentic glomerulonephritis, IgA nephropathy, membranoproliferative glomerulonephritis membranous nephropathy, pyelonephritis and idiopathic renal hematuria. A remarkable increase of CD56 cells in urine was observed in glomerulonephritis with marked necrotizing/and or crescentic (NC) lesions. The ratio of CD56+ cells/CD3+ cells was correlated with the severity of NC lesions. The ratio of CD14+ cells/CD3+ cells was increased in glomerulonephritis with endocapillary proliferation. Using immunohistochemical methods, CD56+ cells were also observed to be present in cellular crescents in biopsy specimens. These observations suggest that an analysis of these cells in urine using flow cytometry may be a useful tool for monitoring disease activity in proliferative glomerulonephritis."} {"id": "PMID:1282575", "title": "Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages.", "content": "Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.", "contents": "Inhibitory action of tranilast, an anti-allergic drug, on the release of cytokines and PGE2 from human monocytes-macrophages. Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages."} {"id": "PMID:1282576", "title": "The mechanism involved in the inhibitory action of tranilast on collagen biosynthesis of keloid fibroblasts.", "content": "Tranilast, an anti-allergic drug inhibiting the release of substances such as histamine and prostaglandins from mast cells, was previously reported to suppress collagen synthesis of fibroblasts derived from keloid tissues. However, the inhibitory mechanism on collagen synthesis is unknown. We studied its inhibitory mechanism on collagen synthesis by culturing fibroblasts from keloid and hypertrophic scar tissues of humans. Collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue is greater than that from healthy human skin. Tranilast (3-100 microM) did not inhibit prolyl hydroxylase (the rate-limiting enzyme in collagen synthesis) activity. Tranilast (3-300 microM) suppressed the collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue but not healthy skin fibroblasts. Tranilast (30-300 microM) inhibited the release of transforming growth factor (TGF)-beta 1 from keloid fibroblasts, which enhances the collagen synthesis of keloid fibroblasts. Anti-TGF-beta 1 antibody (50 microliter/ml) inhibited the collagen synthesis, although diphenhydramine (10 microM) and indomethacin (10 microM) did not show any inhibition. These results suggest that tranilast inhibits collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue through suppressing the release of TGF-beta 1 from the fibroblasts themselves.", "contents": "The mechanism involved in the inhibitory action of tranilast on collagen biosynthesis of keloid fibroblasts. Tranilast, an anti-allergic drug inhibiting the release of substances such as histamine and prostaglandins from mast cells, was previously reported to suppress collagen synthesis of fibroblasts derived from keloid tissues. However, the inhibitory mechanism on collagen synthesis is unknown. We studied its inhibitory mechanism on collagen synthesis by culturing fibroblasts from keloid and hypertrophic scar tissues of humans. Collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue is greater than that from healthy human skin. Tranilast (3-100 microM) did not inhibit prolyl hydroxylase (the rate-limiting enzyme in collagen synthesis) activity. Tranilast (3-300 microM) suppressed the collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue but not healthy skin fibroblasts. Tranilast (30-300 microM) inhibited the release of transforming growth factor (TGF)-beta 1 from keloid fibroblasts, which enhances the collagen synthesis of keloid fibroblasts. Anti-TGF-beta 1 antibody (50 microliter/ml) inhibited the collagen synthesis, although diphenhydramine (10 microM) and indomethacin (10 microM) did not show any inhibition. These results suggest that tranilast inhibits collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue through suppressing the release of TGF-beta 1 from the fibroblasts themselves."} {"id": "PMID:1282577", "title": "[Clinical significance of urinary flow pattern--based on combined uroflowmetry and external sphincter electromyography].", "content": "We performed combined uroflowmetry and external sphincter electromyography in 108 patients (87 males and 21 females); 16 serving as normal controls, 49 with benign prostatic hyperplasia, 16 with overactive type of neurogenic bladder, 27 with underactive type of neurogenic bladder. Urinary flow pattern was classified into 5 categories. All of urinary flow patterns of normal controls showed pattern A which had the form of a bell. EMG showed complete suppression during micturition followed by a few intermittent increases in amplitude. Urinary flow patterns of BPH patients were distributed widely from pattern A to E. Intermittent increases in EMG amplitude during a late phase of micturition were characteristic in patients with BPH. We must pay attention to sex differences to evaluate urinary flow pattern because it could be influenced by abdominal pressure such as stressing or Cr\u00e9de maneuver in female patients with an underactive type of neurogenic bladder.", "contents": "[Clinical significance of urinary flow pattern--based on combined uroflowmetry and external sphincter electromyography]. We performed combined uroflowmetry and external sphincter electromyography in 108 patients (87 males and 21 females); 16 serving as normal controls, 49 with benign prostatic hyperplasia, 16 with overactive type of neurogenic bladder, 27 with underactive type of neurogenic bladder. Urinary flow pattern was classified into 5 categories. All of urinary flow patterns of normal controls showed pattern A which had the form of a bell. EMG showed complete suppression during micturition followed by a few intermittent increases in amplitude. Urinary flow patterns of BPH patients were distributed widely from pattern A to E. Intermittent increases in EMG amplitude during a late phase of micturition were characteristic in patients with BPH. We must pay attention to sex differences to evaluate urinary flow pattern because it could be influenced by abdominal pressure such as stressing or Cr\u00e9de maneuver in female patients with an underactive type of neurogenic bladder."} {"id": "PMID:1282578", "title": "[Production of polyclonal antibody against human androgen receptor and immunohistochemical study of human androgen receptor in prostatic tissues].", "content": "We produced polyclonal antibody against human androgen receptor (hAR) by means of immunizing a rabbit with hAR fusion protein that was expressed in E. coli. In Western blot analysis, this antibody, NH27, recognized two protein bands at the site of 110 kDa and 107 kDa in androgen-independent human prostatic cancer cells (PC-3), transfected with full-length hAR expression plasmid DNA and at the site of 114 kDa and 108 kDa in androgen-dependent human prostatic cancer cells (LNCaP). In immunohistochemical examination with NH27, the nuclei of epithelial and stromal cells in human benign prostatic hyperplasia were mainly stained as did with AN1-15, commercially available hAR monoclonal antibody. Titer of NH27, however, was about five times more high than that of AN1-15. In prostatic cancer cells the nuclei were stained with NH27 as did with AN1-15. Intensity of staining was various between the nuclei of cancer cells. The polyclonal antibody, NH27, produced in the present study is useful in investigating the characterization of AR in androgen-dependent and -independent prostatic cancers.", "contents": "[Production of polyclonal antibody against human androgen receptor and immunohistochemical study of human androgen receptor in prostatic tissues]. We produced polyclonal antibody against human androgen receptor (hAR) by means of immunizing a rabbit with hAR fusion protein that was expressed in E. coli. In Western blot analysis, this antibody, NH27, recognized two protein bands at the site of 110 kDa and 107 kDa in androgen-independent human prostatic cancer cells (PC-3), transfected with full-length hAR expression plasmid DNA and at the site of 114 kDa and 108 kDa in androgen-dependent human prostatic cancer cells (LNCaP). In immunohistochemical examination with NH27, the nuclei of epithelial and stromal cells in human benign prostatic hyperplasia were mainly stained as did with AN1-15, commercially available hAR monoclonal antibody. Titer of NH27, however, was about five times more high than that of AN1-15. In prostatic cancer cells the nuclei were stained with NH27 as did with AN1-15. Intensity of staining was various between the nuclei of cancer cells. The polyclonal antibody, NH27, produced in the present study is useful in investigating the characterization of AR in androgen-dependent and -independent prostatic cancers."} {"id": "PMID:1282579", "title": "[Evaluation of renal function and prediction of renal functional recovery in children with unilateral hydronephrosis using renal pelvic urine].", "content": "In 29 children with unilateral hydronephrosis who underwent surgery at the age from 2 months to 15 years (27 patients with ureteropelvic junction stenosis and 2 with obstructive megaureter), beta 2-microglobulin (beta 2-MG), alpha 1-microglobulin (alpha 1-MG), N-acetyl-beta-D-glucosaminidase (NAG) and albumin were determined in renal pelvic urine from the hydronephrotic kidney to evaluate renal dysfunction accompanying urinary tract obstruction. Moreover, it was also examined whether it is possible to predict functional recovery of the hydronephrotic kidney on the basis of relation between these indices and pre- and postoperative changes in renal dimercaptosuccinic acid (DMSA) uptake rate. The values of beta 2-MG, alpha 1-MG, NAG and albumin in urine from the renal pelvis were high in 48%, 50%, 75% and 83% of the patients, respectively. Among the patients of one year and up, those with low preoperative DMSA uptake rate tended to have high values of beta 2-MG, alpha 1-MG and NAG. On the contrary, albumin level was high in 78% of patients who had good preoperative DMSA uptake rate. With respect to the relation between pre- and postoperative changes in DMSA uptake rate and each index, beta 2-MG and alpha 1-MG were high in 73% and 62% of patients who exhibited a marked increase in postoperative DMSA uptake rate. In patients without a remarkable change in DMSA uptake rate before and after surgery, on the other hand, the values of these were high only in 25% and 36%.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Evaluation of renal function and prediction of renal functional recovery in children with unilateral hydronephrosis using renal pelvic urine]. In 29 children with unilateral hydronephrosis who underwent surgery at the age from 2 months to 15 years (27 patients with ureteropelvic junction stenosis and 2 with obstructive megaureter), beta 2-microglobulin (beta 2-MG), alpha 1-microglobulin (alpha 1-MG), N-acetyl-beta-D-glucosaminidase (NAG) and albumin were determined in renal pelvic urine from the hydronephrotic kidney to evaluate renal dysfunction accompanying urinary tract obstruction. Moreover, it was also examined whether it is possible to predict functional recovery of the hydronephrotic kidney on the basis of relation between these indices and pre- and postoperative changes in renal dimercaptosuccinic acid (DMSA) uptake rate. The values of beta 2-MG, alpha 1-MG, NAG and albumin in urine from the renal pelvis were high in 48%, 50%, 75% and 83% of the patients, respectively. Among the patients of one year and up, those with low preoperative DMSA uptake rate tended to have high values of beta 2-MG, alpha 1-MG and NAG. On the contrary, albumin level was high in 78% of patients who had good preoperative DMSA uptake rate. With respect to the relation between pre- and postoperative changes in DMSA uptake rate and each index, beta 2-MG and alpha 1-MG were high in 73% and 62% of patients who exhibited a marked increase in postoperative DMSA uptake rate. In patients without a remarkable change in DMSA uptake rate before and after surgery, on the other hand, the values of these were high only in 25% and 36%.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282580", "title": "[Prostate cancer after subcapsular prostatectomy diagnosed as benign prostate hypertrophy--clinico-pathological analysis].", "content": "Of 160 newly diagnosed cases of prostate cancer during last 11 years, six (3.75%) had a prior subcapsular prostatectomy. Digital rectal examination in these six cases revealed a significant prostatic abnormality and multiple bone metastases were showed. Histological examination by step-section technique was done retrospectively using surgical materials from subcapsular prostatectomy. Two cases of incidental carcinoma were detected histologically. One showed stage A1 and another stage A2. Continuous observation should be performed after prostatectomy, even if the surgical specimens revealed no carcinoma.", "contents": "[Prostate cancer after subcapsular prostatectomy diagnosed as benign prostate hypertrophy--clinico-pathological analysis]. Of 160 newly diagnosed cases of prostate cancer during last 11 years, six (3.75%) had a prior subcapsular prostatectomy. Digital rectal examination in these six cases revealed a significant prostatic abnormality and multiple bone metastases were showed. Histological examination by step-section technique was done retrospectively using surgical materials from subcapsular prostatectomy. Two cases of incidental carcinoma were detected histologically. One showed stage A1 and another stage A2. Continuous observation should be performed after prostatectomy, even if the surgical specimens revealed no carcinoma."} {"id": "PMID:1282581", "title": "Production and epidemiological application of monoclonal antibody specific for Salmonella O5-antigen.", "content": "Salmonella typhimurium is an important causative agent of acute gastroenteritis (food poisoning), and the decision of the source of infection urgently requires epidemiological investigation. There are two types of S. typhimurium, O5-antigen-carrier type (O5(+)-antigen type) and noncarrier type (Copenhagen antigen type). On the assumption that serological differentiation of the types is effective for epidemiological exploration for the source of infection, we produced a monoclonal antibody, TMY1, specific for the O5-antigen. We classified S. typhimurium identified as the causative agent of mass outbreaks of acute Salmonella gastroenteritis according to the O5-antigen type, by using the TMY1. As a result, the bacterium in each outbreak was classified as the O5(+)-antigen type or the Copenhagen antigen type based on the difference in reactivity with TMY1. S. typhimurium isolated from calves in mass outbreaks of diarrhea and from animals with various diseases were also classified by TMY1 according to the O5-antigen type, and TMY1 was found to be as useful as in human cases. From this confirmation, TMY1 was demonstrated to be useful as a marker for epidemiological investigation of the source of infection by the O5-antigen type of S. typhimurium.", "contents": "Production and epidemiological application of monoclonal antibody specific for Salmonella O5-antigen. Salmonella typhimurium is an important causative agent of acute gastroenteritis (food poisoning), and the decision of the source of infection urgently requires epidemiological investigation. There are two types of S. typhimurium, O5-antigen-carrier type (O5(+)-antigen type) and noncarrier type (Copenhagen antigen type). On the assumption that serological differentiation of the types is effective for epidemiological exploration for the source of infection, we produced a monoclonal antibody, TMY1, specific for the O5-antigen. We classified S. typhimurium identified as the causative agent of mass outbreaks of acute Salmonella gastroenteritis according to the O5-antigen type, by using the TMY1. As a result, the bacterium in each outbreak was classified as the O5(+)-antigen type or the Copenhagen antigen type based on the difference in reactivity with TMY1. S. typhimurium isolated from calves in mass outbreaks of diarrhea and from animals with various diseases were also classified by TMY1 according to the O5-antigen type, and TMY1 was found to be as useful as in human cases. From this confirmation, TMY1 was demonstrated to be useful as a marker for epidemiological investigation of the source of infection by the O5-antigen type of S. typhimurium."} {"id": "PMID:1282583", "title": "Naftopidil, a new adrenoceptor blocking agent with Ca(2+)-antagonistic properties: interaction with adrenoceptors.", "content": "The interaction of naftopidil with adrenoceptors was studied in comparison to standard drugs. Naftopidil binds specifically to alpha 1-adrenoceptors. The Ki values are 58.3 nM for naftopidil, 0.43 nM for prazosin, and 197 nM for urapidil. The affinities of naftopidil to alpha 2- and beta-adrenoceptor sites are very low (> 6,000 and > 2,500 nM). Naftopidil relaxes aortic strips precontracted with norepinephrine concentration-dependently, and it shifts the concentration-response curve of norepinephrine in a parallel manner to the right. The pA2 values are 7.10 for naftopidil, 8.85 for prazosin, and 6.25 for urapidil. In pithed rats, naftopidil shifted the dose-response curve of methoxamine at equipotent hypotensive doses to the same extent to the right as does prazosin, but both drugs barely affected (in contrast to phentolamine) the response to norepinephrine. In concentrations that are about 10 times higher than those required for alpha 1-adrenoceptor blockade, naftopidil relaxes (in contrast to prazosin) aortic strips depolarized with K+, and it shifts Ca2+ concentration-response curves to the right (pA2 value of 5.90), thus suggesting Ca(2+)-channel-blocking activity. Both alpha-adrenoceptor and Ca(2+)-blocking activities are exerted to nearly the same extent by both stereoisomers. Naftipidil does not affect the response to isoprenaline-induced effects, indicating that the compound does not possess beta-blocking properties.", "contents": "Naftopidil, a new adrenoceptor blocking agent with Ca(2+)-antagonistic properties: interaction with adrenoceptors. The interaction of naftopidil with adrenoceptors was studied in comparison to standard drugs. Naftopidil binds specifically to alpha 1-adrenoceptors. The Ki values are 58.3 nM for naftopidil, 0.43 nM for prazosin, and 197 nM for urapidil. The affinities of naftopidil to alpha 2- and beta-adrenoceptor sites are very low (> 6,000 and > 2,500 nM). Naftopidil relaxes aortic strips precontracted with norepinephrine concentration-dependently, and it shifts the concentration-response curve of norepinephrine in a parallel manner to the right. The pA2 values are 7.10 for naftopidil, 8.85 for prazosin, and 6.25 for urapidil. In pithed rats, naftopidil shifted the dose-response curve of methoxamine at equipotent hypotensive doses to the same extent to the right as does prazosin, but both drugs barely affected (in contrast to phentolamine) the response to norepinephrine. In concentrations that are about 10 times higher than those required for alpha 1-adrenoceptor blockade, naftopidil relaxes (in contrast to prazosin) aortic strips depolarized with K+, and it shifts Ca2+ concentration-response curves to the right (pA2 value of 5.90), thus suggesting Ca(2+)-channel-blocking activity. Both alpha-adrenoceptor and Ca(2+)-blocking activities are exerted to nearly the same extent by both stereoisomers. Naftipidil does not affect the response to isoprenaline-induced effects, indicating that the compound does not possess beta-blocking properties."} {"id": "PMID:1282584", "title": "Effects of the selective neutral endopeptidase inhibitor, retrothiorphan, on renal function and blood pressure in conscious normotensive Wistar and hypertensive DOCA-salt rats.", "content": "Atrial natriuretic peptide (ANP) is degraded by neutral endopeptidase (NEP) mainly in the proximal tubule of the kidneys. We studied the effects of retrothiorphan, a potent and highly specific NEP inhibitor on renal function and blood pressure (BP). A 25-mg/kg bolus injection (group bolus), or bolus injection plus infusion 25 mg/kg + 25 mg/kg/h (group infusion), was given to conscious normotensive Wistar and hypertensive DOCA-salt rats. Bolus and infusion produced increases in diuresis (110 +/- 15 vs. 103 +/- 15 vs. 42 +/- 9 microliters/min) and natriuresis (10.6 +/- 3.0 vs. 7.0 +/- 1.0 vs. 5.4 +/- 1.0 mumol/min) in normotensive rats, with a maximum change at 30 min. Change in kaliuresis was not significant. These renal effects were associated with nonsignificant increases in urinary cyclic GMP and ANP. Arterial pressure and heart rate (HR) were not affected. Bolus or infusion of retrothiorphan also induced increases in diuresis (92 +/- 16 vs. 124 +/- 13 vs. 38 +/- 6 microliters/min) and natriuresis (10.3 +/- 2.0 vs. 12.5 +/- 1.0 vs. 5.0 +/- 1.0 mumol/min) in DOCA-salt hypertensive rats, with a maximum change at 30 min. The changes in diuresis and natriuresis induced by retrothiorphan were correlated with a significant increase in urinary cyclic GMP excretion (r = 0.89, p < 0.001 and r = 0.91, p < 0.001). Urinary ANP did not change in controls but significantly increased in the treated rats; urinary immunoreactive bradykinin (BK) also tended to increase. Plasma ANP and hematocrit did not change after retrothiorphan, but plasma cyclic GMP increased significantly after infusion. Only infusion caused a decrease in arterial pressure in DOCA-salt rats (-20 mm Hg at 120 min). Renal clearance studies in DOCA-salt rats showed that retrothiorphan has a transient effect on renal hemodynamics, with increases in glomerular filtration and renal blood flow (RBF) and a decrease in renal vascular resistance (RVR). Its renal action was also tubular, with an increase in fractional sodium excretion. We also compared the effects of retrothiorphan in normotensive Brown-Norway kininogen-deficient rats (BN-Kat) and DOCA-salt hypertensive kininogen-deficient rats. The NEP inhibitor induced increases in diuresis and natriuresis in both groups, with increased urinary cyclic GMP. Urinary immunoreactive BK did not change significantly in normotensive or DOCA-salt hypertensive kininogen-deficient rats.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Effects of the selective neutral endopeptidase inhibitor, retrothiorphan, on renal function and blood pressure in conscious normotensive Wistar and hypertensive DOCA-salt rats. Atrial natriuretic peptide (ANP) is degraded by neutral endopeptidase (NEP) mainly in the proximal tubule of the kidneys. We studied the effects of retrothiorphan, a potent and highly specific NEP inhibitor on renal function and blood pressure (BP). A 25-mg/kg bolus injection (group bolus), or bolus injection plus infusion 25 mg/kg + 25 mg/kg/h (group infusion), was given to conscious normotensive Wistar and hypertensive DOCA-salt rats. Bolus and infusion produced increases in diuresis (110 +/- 15 vs. 103 +/- 15 vs. 42 +/- 9 microliters/min) and natriuresis (10.6 +/- 3.0 vs. 7.0 +/- 1.0 vs. 5.4 +/- 1.0 mumol/min) in normotensive rats, with a maximum change at 30 min. Change in kaliuresis was not significant. These renal effects were associated with nonsignificant increases in urinary cyclic GMP and ANP. Arterial pressure and heart rate (HR) were not affected. Bolus or infusion of retrothiorphan also induced increases in diuresis (92 +/- 16 vs. 124 +/- 13 vs. 38 +/- 6 microliters/min) and natriuresis (10.3 +/- 2.0 vs. 12.5 +/- 1.0 vs. 5.0 +/- 1.0 mumol/min) in DOCA-salt hypertensive rats, with a maximum change at 30 min. The changes in diuresis and natriuresis induced by retrothiorphan were correlated with a significant increase in urinary cyclic GMP excretion (r = 0.89, p < 0.001 and r = 0.91, p < 0.001). Urinary ANP did not change in controls but significantly increased in the treated rats; urinary immunoreactive bradykinin (BK) also tended to increase. Plasma ANP and hematocrit did not change after retrothiorphan, but plasma cyclic GMP increased significantly after infusion. Only infusion caused a decrease in arterial pressure in DOCA-salt rats (-20 mm Hg at 120 min). Renal clearance studies in DOCA-salt rats showed that retrothiorphan has a transient effect on renal hemodynamics, with increases in glomerular filtration and renal blood flow (RBF) and a decrease in renal vascular resistance (RVR). Its renal action was also tubular, with an increase in fractional sodium excretion. We also compared the effects of retrothiorphan in normotensive Brown-Norway kininogen-deficient rats (BN-Kat) and DOCA-salt hypertensive kininogen-deficient rats. The NEP inhibitor induced increases in diuresis and natriuresis in both groups, with increased urinary cyclic GMP. Urinary immunoreactive BK did not change significantly in normotensive or DOCA-salt hypertensive kininogen-deficient rats.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282582", "title": "[Spiro-ergometric studies after corrective surgery of tetralogy of Fallot].", "content": "Treadmill exercise electrocardiography and spirometry was recorded in 61 patients (aged from 5 to 23 years) who underwent corrective surgery for tetralogy of Fallot. The Bruce-protocol and a modified interval-protocol were compared to find out their ability to induce arrhythmias. Supraventricular arrhythmias were predominantly provoked by the interval-protocol while maximal exhaustion is often necessary for inducing ventricular arrhythmias which we found in 23% of our patients. Most of them were seen in the periods of recovery between or after the exercise. We propose a combination of both protocols, which will be compared with established forms of exercise-testing in further studies. The results of rhythm analysis of consecutive exercise tests in one patient after surgical repair could possibly be compared by using an \"arrhythmia score\" which tries to indicate the severity of different forms of arrhythmias. The values of maximal heart rate, oxygen consumption and endurance time recorded at maximal exercise (Bruce-protocol) were about 15% lower than correspondent values of healthy persons found by other authors.", "contents": "[Spiro-ergometric studies after corrective surgery of tetralogy of Fallot]. Treadmill exercise electrocardiography and spirometry was recorded in 61 patients (aged from 5 to 23 years) who underwent corrective surgery for tetralogy of Fallot. The Bruce-protocol and a modified interval-protocol were compared to find out their ability to induce arrhythmias. Supraventricular arrhythmias were predominantly provoked by the interval-protocol while maximal exhaustion is often necessary for inducing ventricular arrhythmias which we found in 23% of our patients. Most of them were seen in the periods of recovery between or after the exercise. We propose a combination of both protocols, which will be compared with established forms of exercise-testing in further studies. The results of rhythm analysis of consecutive exercise tests in one patient after surgical repair could possibly be compared by using an \"arrhythmia score\" which tries to indicate the severity of different forms of arrhythmias. The values of maximal heart rate, oxygen consumption and endurance time recorded at maximal exercise (Bruce-protocol) were about 15% lower than correspondent values of healthy persons found by other authors."} {"id": "PMID:1282585", "title": "Arterial and antihypertensive effects of nitrendipine: a double-blind comparison versus placebo.", "content": "Arterial effects evaluated by carotid-femoral, brachial-radial, and femoral-tibial pulse wave velocity and antihypertensive effect evaluated by 24-h ambulatory blood pressure (BP) monitoring were measured in 17 hypertensive patients before and 24 h after once-daily nitrendipine (20 mg) administration. After a 15-day placebo period, a double-blind study of nitrendipine versus placebo was performed for 1 month. After nitrendipine dosing, BP measured by sphygmomanometer 24 h after the last drug intake showed a significant decrease as compared with the pretreatment period. Ambulatory BP mean values were also significantly decreased for systolic and diastolic BP (SBP, DBP). This decrease predominated during the day but was observed nocturnally only after 6 a.m. Twenty-four hours after the last tablet intake of nitrendipine, carotid-femoral and brachial-radial pulse wave velocities were significantly reduced, whereas femoral-tibial wave velocity was unchanged, indicating that markers of arterial rigidity might be substantially modified and that the modifications were partly unrelated to BP changes. The results provide evidence that in hypertensive subjects nitrendipine 20 mg given once daily for 1 month produces an arterial effect for 24 h, in association with BP reduction.", "contents": "Arterial and antihypertensive effects of nitrendipine: a double-blind comparison versus placebo. Arterial effects evaluated by carotid-femoral, brachial-radial, and femoral-tibial pulse wave velocity and antihypertensive effect evaluated by 24-h ambulatory blood pressure (BP) monitoring were measured in 17 hypertensive patients before and 24 h after once-daily nitrendipine (20 mg) administration. After a 15-day placebo period, a double-blind study of nitrendipine versus placebo was performed for 1 month. After nitrendipine dosing, BP measured by sphygmomanometer 24 h after the last drug intake showed a significant decrease as compared with the pretreatment period. Ambulatory BP mean values were also significantly decreased for systolic and diastolic BP (SBP, DBP). This decrease predominated during the day but was observed nocturnally only after 6 a.m. Twenty-four hours after the last tablet intake of nitrendipine, carotid-femoral and brachial-radial pulse wave velocities were significantly reduced, whereas femoral-tibial wave velocity was unchanged, indicating that markers of arterial rigidity might be substantially modified and that the modifications were partly unrelated to BP changes. The results provide evidence that in hypertensive subjects nitrendipine 20 mg given once daily for 1 month produces an arterial effect for 24 h, in association with BP reduction."} {"id": "PMID:1282586", "title": "Effects of nifedipine and diltiazem on myocardial ischemia in patients with severe stable angina pectoris treated with nitrates and beta-blockers.", "content": "In a randomized, cross-over, double-blind study, the effects of nifedipine were compared with those of diltiazem in 20 patients with severe stable angina pectoris and multivessel coronary artery disease treated with nitrates and beta-blockers. The comparison was performed by bicycle ergometry, clinical evaluation, and ambulatory 24-h ECG monitoring for 7-8 weeks. As compared with placebo, both nifedipine and diltiazem significantly reduced the daily number of anginal attacks and nitroglycerin consumption; prolonged exercise duration, time to 1-mm ST segment depression, and to onset of angina; and reduced the sum of ST segment depressions at maximal identical load in ergometry. In ambulatory ECG monitoring, only nifedipine significantly diminished the duration of asymptomatic ST segment depression as compared with placebo. Antianginal and antiischemic effects of nifedipine and diltiazem were similar. Both nifedipine and diltiazem significantly increased the effects of treatment with nitrates and beta-blockers. Administration of nifedipine was safer because at night diltiazem caused significant bradycardia despite careful titration of optimum doses of the drug. Although the maximum well-tolerated doses of conventional medication suppressed anginal symptoms in some patients, they did not abolish ischemia either at ergometry or in daily life.", "contents": "Effects of nifedipine and diltiazem on myocardial ischemia in patients with severe stable angina pectoris treated with nitrates and beta-blockers. In a randomized, cross-over, double-blind study, the effects of nifedipine were compared with those of diltiazem in 20 patients with severe stable angina pectoris and multivessel coronary artery disease treated with nitrates and beta-blockers. The comparison was performed by bicycle ergometry, clinical evaluation, and ambulatory 24-h ECG monitoring for 7-8 weeks. As compared with placebo, both nifedipine and diltiazem significantly reduced the daily number of anginal attacks and nitroglycerin consumption; prolonged exercise duration, time to 1-mm ST segment depression, and to onset of angina; and reduced the sum of ST segment depressions at maximal identical load in ergometry. In ambulatory ECG monitoring, only nifedipine significantly diminished the duration of asymptomatic ST segment depression as compared with placebo. Antianginal and antiischemic effects of nifedipine and diltiazem were similar. Both nifedipine and diltiazem significantly increased the effects of treatment with nitrates and beta-blockers. Administration of nifedipine was safer because at night diltiazem caused significant bradycardia despite careful titration of optimum doses of the drug. Although the maximum well-tolerated doses of conventional medication suppressed anginal symptoms in some patients, they did not abolish ischemia either at ergometry or in daily life."} {"id": "PMID:1282587", "title": "Effects of pirenzepine and hexamethonium on adrenal catecholamine release in responses to endogenous and exogenous acetylcholine in anesthetized dogs.", "content": "We investigated the way in which hexamethonium and pirenzepine, a selective muscarinic (M) 1 receptor antagonist, modify the release of catecholamines from dog adrenal gland in response to endogenous and exogenous acetylcholine (ACh) in vivo. Output of epinephrine (EPI), and norepinephrine (NE) was determined from adrenal venous blood by high-performance liquid chromatography (HPLC) with electrochemical detection. Intraarterial (i.a.) injections of ACh (1.5 and 3 micrograms) or muscarine (3 and 6 micrograms) into the phrenicoabdominal artery and splanchnic nerve stimulation (SNS, 3 Hz) produced marked increases in EPI and NE output. Hexamethonium (1 mg/kg intravenously, i.v.) inhibited the increases in EPI and NE output in response to exogenous ACh and SNS. Pirenzepine (10 micrograms/kg i.v.) inhibited the ACh-induced increases in EPI and NE output but did not modify the SNS-induced increases. The muscarine-induced increases in EPI and NE output were also inhibited by pirenzepine. These results indicate that the exogenous ACh-induced release of adrenal catecholamines is mediated through both nicotinic and M1 receptors, in contrast to the predominant mediation of nicotinic receptors in response to endogenous ACh.", "contents": "Effects of pirenzepine and hexamethonium on adrenal catecholamine release in responses to endogenous and exogenous acetylcholine in anesthetized dogs. We investigated the way in which hexamethonium and pirenzepine, a selective muscarinic (M) 1 receptor antagonist, modify the release of catecholamines from dog adrenal gland in response to endogenous and exogenous acetylcholine (ACh) in vivo. Output of epinephrine (EPI), and norepinephrine (NE) was determined from adrenal venous blood by high-performance liquid chromatography (HPLC) with electrochemical detection. Intraarterial (i.a.) injections of ACh (1.5 and 3 micrograms) or muscarine (3 and 6 micrograms) into the phrenicoabdominal artery and splanchnic nerve stimulation (SNS, 3 Hz) produced marked increases in EPI and NE output. Hexamethonium (1 mg/kg intravenously, i.v.) inhibited the increases in EPI and NE output in response to exogenous ACh and SNS. Pirenzepine (10 micrograms/kg i.v.) inhibited the ACh-induced increases in EPI and NE output but did not modify the SNS-induced increases. The muscarine-induced increases in EPI and NE output were also inhibited by pirenzepine. These results indicate that the exogenous ACh-induced release of adrenal catecholamines is mediated through both nicotinic and M1 receptors, in contrast to the predominant mediation of nicotinic receptors in response to endogenous ACh."} {"id": "PMID:1282588", "title": "Neurohormonal and blood pressure responses to low-dose infusion of an orally active renin inhibitor, Ro 42-5892, in salt-replete men.", "content": "Renin inhibitors are an alternative means of blockade of circulating and tissue-based renin-angiotensin systems (RAS). We studied a new renin inhibitor, Ro 42-5892, by low-dose (0.1 mg/kg) intravenous (i.v.) infusion in 10 min (fast) or 6 h (slow) or placebo in a double-blind cross-over study to assess the relationship between drug concentration and response. Fasting salt-replete normotensive male volunteers (n = 9) aged 18-32 years were studied supine. There were no significant changes in blood pressure (BP) or heart rate (HR) between drug and placebo infusion. Drug concentration peaked (482 +/- 140 ng/ml) at the end of the fast infusion or showed a sustained plateau (25.9 +/- 6.1 ng/ml) with the slow infusion (mean time to peak 121 +/- 99 min). Both fast (135.2 +/- 26 ng/ml/h2) and slow (121.0 +/- 31.1 ng/ml/h2) infusions had similar area under the curve (AUC)0-24-values. Plasma renin activity (PRA) was dramatically reduced by both strategies, but AUC0-10 for PRA was significantly less for slow (1.7 +/- 0.6 ngAI/ml/h2) than fast (4.9 +/- 2.5 ngAI/ml/h2) infusions. Mean peak plasma active renin (AR) concentration was increased by both fast (102.2 +/- 65.9 pg/ml) and slow (195.2 +/- 110.5 pg/ml) infusions as compared with placebo (49.9 +/- 18.6 pg/ml). Similarly, AUC0-10 for AR was greater for slow (990.2 +/- 582.1 pg/ml/h) than fast (512.4 +/- 189.4 pg/ml/h) infusions. Plasma angiotensin-converting enzyme (ACE) activity was unaltered. Our results indicate that protracted low concentrations of Ro 42-5892 may provide more effective and long-lasting inhibition of renin.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Neurohormonal and blood pressure responses to low-dose infusion of an orally active renin inhibitor, Ro 42-5892, in salt-replete men. Renin inhibitors are an alternative means of blockade of circulating and tissue-based renin-angiotensin systems (RAS). We studied a new renin inhibitor, Ro 42-5892, by low-dose (0.1 mg/kg) intravenous (i.v.) infusion in 10 min (fast) or 6 h (slow) or placebo in a double-blind cross-over study to assess the relationship between drug concentration and response. Fasting salt-replete normotensive male volunteers (n = 9) aged 18-32 years were studied supine. There were no significant changes in blood pressure (BP) or heart rate (HR) between drug and placebo infusion. Drug concentration peaked (482 +/- 140 ng/ml) at the end of the fast infusion or showed a sustained plateau (25.9 +/- 6.1 ng/ml) with the slow infusion (mean time to peak 121 +/- 99 min). Both fast (135.2 +/- 26 ng/ml/h2) and slow (121.0 +/- 31.1 ng/ml/h2) infusions had similar area under the curve (AUC)0-24-values. Plasma renin activity (PRA) was dramatically reduced by both strategies, but AUC0-10 for PRA was significantly less for slow (1.7 +/- 0.6 ngAI/ml/h2) than fast (4.9 +/- 2.5 ngAI/ml/h2) infusions. Mean peak plasma active renin (AR) concentration was increased by both fast (102.2 +/- 65.9 pg/ml) and slow (195.2 +/- 110.5 pg/ml) infusions as compared with placebo (49.9 +/- 18.6 pg/ml). Similarly, AUC0-10 for AR was greater for slow (990.2 +/- 582.1 pg/ml/h) than fast (512.4 +/- 189.4 pg/ml/h) infusions. Plasma angiotensin-converting enzyme (ACE) activity was unaltered. Our results indicate that protracted low concentrations of Ro 42-5892 may provide more effective and long-lasting inhibition of renin.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282589", "title": "Postjunctional alpha-adrenergic stimulation of inotropy in hypoperfused myocardium outside an acute infarct.", "content": "The functional significance of myocardial postjunctional alpha-adrenergic support of inotropy in the vicinity of an acute regional ischemic zone was addressed in pentobarbital-anesthetized, beta-adrenergic blocked cats with circumflex coronary artery occlusion. Regional myocardial performance was measured by ultrasonic crystals in the anterior wall perfused by the left anterior descending coronary artery (LAD) before and during postjunctional alpha-adrenergic antagonism (SK&F 104078 2 mg/kg). A group with unrestricted flow in the LAD (control group) was compared with a group perfused below the autoregulatory pressure range (stenosis group). End-systolic pressure-length relations during dynamic after-load elevation were calculated for assessment of regional contractility. Regional myocardial blood flow (RMBF) was measured by radioactive microspheres. SK&F 104078 did not alter regional myocardial shortening or the slope of end-systolic pressure-length relations in the control group. In the stenosis group, however, alpha-adrenergic antagonism produced significant deterioration of shortening as well as consistent reduction of the slope of the end-systolic pressure-length relations (p < 0.05). As a reflection of reduced demands for perfusion, impairment of midmyocardial and endocardial blood flow occurred in the stenosis group (p < 0.05). These findings imply a negative inotropic effect of SK&F 104078 in metabolically vasodilated myocardium in the vicinity of an acute ischemic region.", "contents": "Postjunctional alpha-adrenergic stimulation of inotropy in hypoperfused myocardium outside an acute infarct. The functional significance of myocardial postjunctional alpha-adrenergic support of inotropy in the vicinity of an acute regional ischemic zone was addressed in pentobarbital-anesthetized, beta-adrenergic blocked cats with circumflex coronary artery occlusion. Regional myocardial performance was measured by ultrasonic crystals in the anterior wall perfused by the left anterior descending coronary artery (LAD) before and during postjunctional alpha-adrenergic antagonism (SK&F 104078 2 mg/kg). A group with unrestricted flow in the LAD (control group) was compared with a group perfused below the autoregulatory pressure range (stenosis group). End-systolic pressure-length relations during dynamic after-load elevation were calculated for assessment of regional contractility. Regional myocardial blood flow (RMBF) was measured by radioactive microspheres. SK&F 104078 did not alter regional myocardial shortening or the slope of end-systolic pressure-length relations in the control group. In the stenosis group, however, alpha-adrenergic antagonism produced significant deterioration of shortening as well as consistent reduction of the slope of the end-systolic pressure-length relations (p < 0.05). As a reflection of reduced demands for perfusion, impairment of midmyocardial and endocardial blood flow occurred in the stenosis group (p < 0.05). These findings imply a negative inotropic effect of SK&F 104078 in metabolically vasodilated myocardium in the vicinity of an acute ischemic region."} {"id": "PMID:1282590", "title": "Electromechanical action of dofetilide and D-sotalol during simulated metabolic acidosis in isolated guinea pig ventricular muscle.", "content": "We examined the electromechanical effects of two class III antiarrhythmic agents, dofetilide (UK-68,798) and D-sotalol, in acidic myocardium. Right ventricular papillary muscle preparations isolated from guinea pigs were divided into three groups (n = 6 per group): (a) drug-free, (b) dofetilide (10 nM), and (c) D-sotalol (30 microM). At normal extracellular pH (pH = 7.32 +/- 0.01), dofetilide and D-sotalol lengthened action potential duration (APD) to a similar extent, i.e., by 18-20%. Effective refractory period (ERP) increased in parallel, whereas membrane diastolic potential (MDP), action potential amplitude (APA), maximum velocity of depolarization (Vmax), and developed force (DF) were not significantly affected. Metabolic acidosis (pH = 6.78 +/- 0.01) was simulated by reducing the bicarbonate concentration of the Tyrode's solution from 20 to 6 mM. Superfusion with acidic solution alone for 30 min markedly decreased Vmax and DF, whereas APD and ERP were lengthened slightly. The acidosis-induced decreases in Vmax and DF were not affected by pretreatment with dofetilide or D-sotalol. In acidic superfusate, both agents still significantly increased APD and ERP to the same extent that they did at normal pH. The results indicate that metabolic acidosis, a major component of myocardial ischemia, does not attenuate the class III antiarrhythmic action of dofetilide and D-sotalol.", "contents": "Electromechanical action of dofetilide and D-sotalol during simulated metabolic acidosis in isolated guinea pig ventricular muscle. We examined the electromechanical effects of two class III antiarrhythmic agents, dofetilide (UK-68,798) and D-sotalol, in acidic myocardium. Right ventricular papillary muscle preparations isolated from guinea pigs were divided into three groups (n = 6 per group): (a) drug-free, (b) dofetilide (10 nM), and (c) D-sotalol (30 microM). At normal extracellular pH (pH = 7.32 +/- 0.01), dofetilide and D-sotalol lengthened action potential duration (APD) to a similar extent, i.e., by 18-20%. Effective refractory period (ERP) increased in parallel, whereas membrane diastolic potential (MDP), action potential amplitude (APA), maximum velocity of depolarization (Vmax), and developed force (DF) were not significantly affected. Metabolic acidosis (pH = 6.78 +/- 0.01) was simulated by reducing the bicarbonate concentration of the Tyrode's solution from 20 to 6 mM. Superfusion with acidic solution alone for 30 min markedly decreased Vmax and DF, whereas APD and ERP were lengthened slightly. The acidosis-induced decreases in Vmax and DF were not affected by pretreatment with dofetilide or D-sotalol. In acidic superfusate, both agents still significantly increased APD and ERP to the same extent that they did at normal pH. The results indicate that metabolic acidosis, a major component of myocardial ischemia, does not attenuate the class III antiarrhythmic action of dofetilide and D-sotalol."} {"id": "PMID:1282591", "title": "Effects of manidipine hydrochloride on the renal microcirculation in spontaneously hypertensive rats.", "content": "We wished to clarify the effects of a newly developed calcium antagonist, manidipine hydrochloride (HCl), on renal microcirculation in hypertensive rats by using the micropuncture technique. Oral administration of manidipine HCl for 2 months reduced systemic blood pressure (BP), did not change the single-nephron glomerular filtration rate (SNGFR), but increased the SNG plasma flow (SNGPF). Moreover, the glomerular transcapillary hydraulic pressure difference (delta P), which is assumed to be the parameter most related to development of glomerulosclerosis, was significantly reduced. Both afferent and efferent arteriolar resistance (RA and RE) were reduced. Intravenous (i.v.) infusion of manidipine HCl (20 micrograms/kg) decreased systemic BP but did not change SNGFR, SNGPF, or delta P. Both RA and RE were also significantly decreased. These results indicate that chronic administration of manidipine HCl increases renal blood flow (RBF) by dilating the afferent arterioles and improves glomerular hypertension by dilating the efferent arterioles. Thus, manidipine HCl might be a beneficial antihypertensive agent for patients with renal diseases. Because acute i.v. infusion of manidipine HCl did not change delta P, apparently time must elapse before glomerular hypertension is corrected.", "contents": "Effects of manidipine hydrochloride on the renal microcirculation in spontaneously hypertensive rats. We wished to clarify the effects of a newly developed calcium antagonist, manidipine hydrochloride (HCl), on renal microcirculation in hypertensive rats by using the micropuncture technique. Oral administration of manidipine HCl for 2 months reduced systemic blood pressure (BP), did not change the single-nephron glomerular filtration rate (SNGFR), but increased the SNG plasma flow (SNGPF). Moreover, the glomerular transcapillary hydraulic pressure difference (delta P), which is assumed to be the parameter most related to development of glomerulosclerosis, was significantly reduced. Both afferent and efferent arteriolar resistance (RA and RE) were reduced. Intravenous (i.v.) infusion of manidipine HCl (20 micrograms/kg) decreased systemic BP but did not change SNGFR, SNGPF, or delta P. Both RA and RE were also significantly decreased. These results indicate that chronic administration of manidipine HCl increases renal blood flow (RBF) by dilating the afferent arterioles and improves glomerular hypertension by dilating the efferent arterioles. Thus, manidipine HCl might be a beneficial antihypertensive agent for patients with renal diseases. Because acute i.v. infusion of manidipine HCl did not change delta P, apparently time must elapse before glomerular hypertension is corrected."} {"id": "PMID:1282592", "title": "Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture.", "content": "Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis.", "contents": "Effect of cilostazol, a cyclic AMP phosphodiesterase inhibitor, on the proliferation of rat aortic smooth muscle cells in culture. Cilostazol, a cyclic AMP phosphodiesterase inhibitor, has been used as an antiplatelet agent. In the present study, we investigated the in vitro effect of cilostazol on DNA synthesis in rat aortic arterial smooth muscle cells (SMCs) in culture stimulated with fetal calf serum (FCS), platelet-derived growth factor (PDGF), insulin, or insulin-like growth factor-I (IGF-I). Micromolar concentrations of cilostazol inhibited [3H]thymidine incorporation into DNA and cell growth as determined by cell number and protein concentration. Treatment with cilostazol increased the intracellular concentration of cyclic AMP, suggesting that the inhibition of SMC proliferation by cilostazol may be mediated through increased levels of cyclic AMP. The results suggested that cilostazol, by interfering with the proliferation of arterial SMCs, may have potential to prevent initiation and progression of atherosclerosis."} {"id": "PMID:1282593", "title": "Desensitization of nitrate-induced venodilation: reversal with oral N-acetylcysteine in humans.", "content": "The objective of this study was to determine whether the dorsal hand vein could be used as a model to study tolerance to oral nitrates, and whether oral N-acetylcysteine (NAC) could reverse tolerance if present. Dose-response curves to nitroglycerin were constructed for 11 normotensive volunteers before and during treatment with a sustained-release formulation of isosorbide dinitrate, 80 mg, three times daily for 7 days and followed by concurrent treatment with NAC at a mean dose of 150 mg/kg/day, in divided doses, for 2 days. In separate studies, dose-response curves were constructed for seven normotensive volunteers before and after treatment with oral NAC at the same dose for 2 days. Nitroglycerin's Emax was significantly attenuated from 115 +/- 36 to 77 +/- 22% after treatment with isosorbide dinitrate alone (p < 0.009). Concurrent treatment with NAC reversed this decrease, as nitroglycerin's Emax of 108 +/- 26% during coadministration of isosorbide dinitrate and NAC was not different from its Emax in the control period. There was also no difference in the dose of phenylephrine required to cause 80% of maximal venoconstriction throughout the study. These studies demonstrate that smooth muscle tolerance to nitrates can be demonstrated in medium-sized veins in humans. In addition, high-dose oral NAC can reverse existing tolerance to oral nitrates in human veins. These results indicate that the dorsal hand vein compliance technique is a good model for the clinical investigation of tolerance to nitrates in humans.", "contents": "Desensitization of nitrate-induced venodilation: reversal with oral N-acetylcysteine in humans. The objective of this study was to determine whether the dorsal hand vein could be used as a model to study tolerance to oral nitrates, and whether oral N-acetylcysteine (NAC) could reverse tolerance if present. Dose-response curves to nitroglycerin were constructed for 11 normotensive volunteers before and during treatment with a sustained-release formulation of isosorbide dinitrate, 80 mg, three times daily for 7 days and followed by concurrent treatment with NAC at a mean dose of 150 mg/kg/day, in divided doses, for 2 days. In separate studies, dose-response curves were constructed for seven normotensive volunteers before and after treatment with oral NAC at the same dose for 2 days. Nitroglycerin's Emax was significantly attenuated from 115 +/- 36 to 77 +/- 22% after treatment with isosorbide dinitrate alone (p < 0.009). Concurrent treatment with NAC reversed this decrease, as nitroglycerin's Emax of 108 +/- 26% during coadministration of isosorbide dinitrate and NAC was not different from its Emax in the control period. There was also no difference in the dose of phenylephrine required to cause 80% of maximal venoconstriction throughout the study. These studies demonstrate that smooth muscle tolerance to nitrates can be demonstrated in medium-sized veins in humans. In addition, high-dose oral NAC can reverse existing tolerance to oral nitrates in human veins. These results indicate that the dorsal hand vein compliance technique is a good model for the clinical investigation of tolerance to nitrates in humans."} {"id": "PMID:1282594", "title": "Effects of WAY-123,398, a new class III antiarrhythmic agent, on cardiac refractoriness and ventricular fibrillation threshold in anesthetized dogs: a comparison with UK-68798, E-4031, and dl-sotalol.", "content": "Previous studies in isolated ventricular myocytes showed that WAY-123,398 is a selective blocker of the delayed rectifier K+ current (IK). In this report, we studied the electrophysiological and hemodynamic effects of WAY-123,398 in open-chest anesthetized dogs. WAY-123,398 prolonged atrial and ventricular refractoriness without affecting conduction; WAY-123,398 was as effective as UK-68798, E-4031, and dl-sotalol, but less potent than UK-68798 and E-4031. The increase in atrial refractoriness was approximately twice as large as the ventricular increase with all compounds. The hemodynamic effects of WAY-123,398 were similar to those of UK-68798; at the ED20 for increasing ventricular refractoriness, WAY-123,398 did not affect the mean arterial pressure and decreased the heart rate by 20%. In a different series of experiments, all four compounds produced large and comparable increases in the ventricular fibrillation threshold in anesthetized dogs; WAY-123,398 and UK-68798 induced defibrillation and restoration of sinus rhythm in two of six dogs each and E-4031 in one of six dogs. No episodes of drug-induced restoration to sinus rhythm were observed in dogs treated with sotalol or vehicle. In conclusion, WAY-123,398 is an effective Class III agent without Class I actions and with a favorable hemodynamic profile.", "contents": "Effects of WAY-123,398, a new class III antiarrhythmic agent, on cardiac refractoriness and ventricular fibrillation threshold in anesthetized dogs: a comparison with UK-68798, E-4031, and dl-sotalol. Previous studies in isolated ventricular myocytes showed that WAY-123,398 is a selective blocker of the delayed rectifier K+ current (IK). In this report, we studied the electrophysiological and hemodynamic effects of WAY-123,398 in open-chest anesthetized dogs. WAY-123,398 prolonged atrial and ventricular refractoriness without affecting conduction; WAY-123,398 was as effective as UK-68798, E-4031, and dl-sotalol, but less potent than UK-68798 and E-4031. The increase in atrial refractoriness was approximately twice as large as the ventricular increase with all compounds. The hemodynamic effects of WAY-123,398 were similar to those of UK-68798; at the ED20 for increasing ventricular refractoriness, WAY-123,398 did not affect the mean arterial pressure and decreased the heart rate by 20%. In a different series of experiments, all four compounds produced large and comparable increases in the ventricular fibrillation threshold in anesthetized dogs; WAY-123,398 and UK-68798 induced defibrillation and restoration of sinus rhythm in two of six dogs each and E-4031 in one of six dogs. No episodes of drug-induced restoration to sinus rhythm were observed in dogs treated with sotalol or vehicle. In conclusion, WAY-123,398 is an effective Class III agent without Class I actions and with a favorable hemodynamic profile."} {"id": "PMID:1282595", "title": "Differences in responses to TC-81 among various arteries in dogs.", "content": "The vasodilation induced by TC-81 was investigated in vitro and in vivo. In helical strips of dog arteries precontracted with 65.4 mM KCl, TC-81, nicardipine, nifedipine, diltiazem, and papaverine produced concentration-dependent relaxation. The potencies of TC-81 were in the following order: basilar > coronary > femoral > renal > mesenteric arteries. The other drugs also showed a similar property of greater response in basilar and coronary arteries than in renal and mesenteric arteries. However, the difference in reactivity to TC-81 was greater. On the other hand, TC-81, nicardipine, and papaverine dose-dependently increased the blood flow in vertebral, coronary, and femoral arteries in anesthetized dogs. However, the blood flow in renal and mesenteric arteries was not changed or decreased. The decreases in vessel resistance induced by TC-81 were in the following order: vertebral > coronary > femoral > renal = mesenteric arteries, agreeing with the experimental results in vitro. These results suggest that Ca2+ antagonists have the pharmacological property of vasodilating cerebral and heart blood vessels more selectively than other arteries, and this property of TC-81 might be an advantage compared with other drugs.", "contents": "Differences in responses to TC-81 among various arteries in dogs. The vasodilation induced by TC-81 was investigated in vitro and in vivo. In helical strips of dog arteries precontracted with 65.4 mM KCl, TC-81, nicardipine, nifedipine, diltiazem, and papaverine produced concentration-dependent relaxation. The potencies of TC-81 were in the following order: basilar > coronary > femoral > renal > mesenteric arteries. The other drugs also showed a similar property of greater response in basilar and coronary arteries than in renal and mesenteric arteries. However, the difference in reactivity to TC-81 was greater. On the other hand, TC-81, nicardipine, and papaverine dose-dependently increased the blood flow in vertebral, coronary, and femoral arteries in anesthetized dogs. However, the blood flow in renal and mesenteric arteries was not changed or decreased. The decreases in vessel resistance induced by TC-81 were in the following order: vertebral > coronary > femoral > renal = mesenteric arteries, agreeing with the experimental results in vitro. These results suggest that Ca2+ antagonists have the pharmacological property of vasodilating cerebral and heart blood vessels more selectively than other arteries, and this property of TC-81 might be an advantage compared with other drugs."} {"id": "PMID:1282596", "title": "Defibrillation energy requirements during moricizine and moricizine-lidocaine therapy.", "content": "Defibrillation energy requirements may be altered by antiarrhythmic agents. We investigated the effects of moricizine on the defibrillation threshold (DFT) in 18 pentobarbital-anesthetized pigs. The animals were randomized, in a blinded fashion, to moricizine or control (0.9% saline) treatment groups. Each group underwent three treatment phases: baseline, drug infusion (moricizine or saline), and drug infusion combined with lidocaine. Moricizine (2 mg/kg loading dose, 1.5 mg/kg/h infusion) and lidocaine (5 mg/kg loading dose, 4 mg/kg/h infusion) were dosed to achieve therapeutic concentrations. After 5 s of induced ventricular fibrillation, defibrillation was performed using a cardiac defibrillator interfaced with two epicardial electrode patches. DFTs were determined at baseline, during the drug phase, and during the combination of lidocaine with moricizine or saline. DFT values in the animals randomized to the control group were 15.2 +/- 4.2, 14.0 +/- 3.3, and 17.8 +/- 8.7 J at baseline, saline infusion, and saline combined with lidocaine, respectively. No significant differences were observed among the treatment phases. DFT values in the animals randomized to moricizine group were 12.1 +/- 2.8, 13.8 +/- 5.2, and 22.9 +/- 7.1 J at baseline, moricizine infusion, and moricizine combined with lidocaine, respectively. The DFT values during the lidocaine-moricizine combination treatment phase were significantly greater than baseline and moricizine alone (p < 0.002). The mean change in the DFT from baseline to moricizine (14% increase) was significantly different than the mean change in the DFT from baseline to saline (8% decrease) (p = 0.03). Lidocaine added to moricizine increased the DFT by 84%, which was significantly different from the 27% increase in the DFT when lidocaine was added to saline (p = 0.02). We conclude that moricizine minimally increases the DFT, but the combination of moricizine with lidocaine results in a synergistic rise in the DFT that may have detrimental clinical implications.", "contents": "Defibrillation energy requirements during moricizine and moricizine-lidocaine therapy. Defibrillation energy requirements may be altered by antiarrhythmic agents. We investigated the effects of moricizine on the defibrillation threshold (DFT) in 18 pentobarbital-anesthetized pigs. The animals were randomized, in a blinded fashion, to moricizine or control (0.9% saline) treatment groups. Each group underwent three treatment phases: baseline, drug infusion (moricizine or saline), and drug infusion combined with lidocaine. Moricizine (2 mg/kg loading dose, 1.5 mg/kg/h infusion) and lidocaine (5 mg/kg loading dose, 4 mg/kg/h infusion) were dosed to achieve therapeutic concentrations. After 5 s of induced ventricular fibrillation, defibrillation was performed using a cardiac defibrillator interfaced with two epicardial electrode patches. DFTs were determined at baseline, during the drug phase, and during the combination of lidocaine with moricizine or saline. DFT values in the animals randomized to the control group were 15.2 +/- 4.2, 14.0 +/- 3.3, and 17.8 +/- 8.7 J at baseline, saline infusion, and saline combined with lidocaine, respectively. No significant differences were observed among the treatment phases. DFT values in the animals randomized to moricizine group were 12.1 +/- 2.8, 13.8 +/- 5.2, and 22.9 +/- 7.1 J at baseline, moricizine infusion, and moricizine combined with lidocaine, respectively. The DFT values during the lidocaine-moricizine combination treatment phase were significantly greater than baseline and moricizine alone (p < 0.002). The mean change in the DFT from baseline to moricizine (14% increase) was significantly different than the mean change in the DFT from baseline to saline (8% decrease) (p = 0.03). Lidocaine added to moricizine increased the DFT by 84%, which was significantly different from the 27% increase in the DFT when lidocaine was added to saline (p = 0.02). We conclude that moricizine minimally increases the DFT, but the combination of moricizine with lidocaine results in a synergistic rise in the DFT that may have detrimental clinical implications."} {"id": "PMID:1282597", "title": "Pharmacologic characterization of an endothelinA (ETA) receptor antagonist in conscious rats.", "content": "The present experiments describe the endothelin-1 (ET-1) antagonist activity of BQ123 (cyclic D-Asp-L-Pro-D-Val-L-Leu-D-Trp) in conscious Sprague-Dawley (SD) rats, and we also examined the effect blockade of ETA receptors had on blood pressure in four experimental models of hypertension. Rats were anesthetized with methoxyflurane and instrumented with femoral arterial and venous catheters. In SD rats, BQ123 (0.1-10.0 mg/kg i.v.) administered 5 or 60 min prior to ET-1 inhibited both the magnitude and duration of the ET-1 (0.25 nmol/kg i.v.) pressor response. In addition, BQ123 (10.0 mg/kg) inhibited the pressor response evoked by administration of the ET-1 precursor, proendothelin-1 (1.0 nmol/kg). However, BQ123 (10.0 mg/kg) had no effect on the pressor response evoked by ET-3 (0.75 nmol/kg). In Wistar-Kyoto rats, BQ123 (10.0 mg/kg) reversed the hypertension produced by an infusion of ET-1 (0.01 nmol/kg/min). Administration of BQ123 produced a mild antihypertensive effect in normal- to low-renin models of hypertension, but no blood pressure lowering was observed in high-renin models of hypertension. These studies demonstrated the selectivity of the ETA receptor antagonist, BQ123 for ET-1, but not ET-3-induced pressor responses. Furthermore, ET-1 does not appear to be a major contributing factor to the maintenance of elevated levels of blood pressure in four experimental models of hypertension.", "contents": "Pharmacologic characterization of an endothelinA (ETA) receptor antagonist in conscious rats. The present experiments describe the endothelin-1 (ET-1) antagonist activity of BQ123 (cyclic D-Asp-L-Pro-D-Val-L-Leu-D-Trp) in conscious Sprague-Dawley (SD) rats, and we also examined the effect blockade of ETA receptors had on blood pressure in four experimental models of hypertension. Rats were anesthetized with methoxyflurane and instrumented with femoral arterial and venous catheters. In SD rats, BQ123 (0.1-10.0 mg/kg i.v.) administered 5 or 60 min prior to ET-1 inhibited both the magnitude and duration of the ET-1 (0.25 nmol/kg i.v.) pressor response. In addition, BQ123 (10.0 mg/kg) inhibited the pressor response evoked by administration of the ET-1 precursor, proendothelin-1 (1.0 nmol/kg). However, BQ123 (10.0 mg/kg) had no effect on the pressor response evoked by ET-3 (0.75 nmol/kg). In Wistar-Kyoto rats, BQ123 (10.0 mg/kg) reversed the hypertension produced by an infusion of ET-1 (0.01 nmol/kg/min). Administration of BQ123 produced a mild antihypertensive effect in normal- to low-renin models of hypertension, but no blood pressure lowering was observed in high-renin models of hypertension. These studies demonstrated the selectivity of the ETA receptor antagonist, BQ123 for ET-1, but not ET-3-induced pressor responses. Furthermore, ET-1 does not appear to be a major contributing factor to the maintenance of elevated levels of blood pressure in four experimental models of hypertension."} {"id": "PMID:1282598", "title": "Endothelium-dependent vasodilation is augmented by angiotensin converting enzyme inhibitors in healthy volunteers.", "content": "We have examined the effects of local intra-arterial infusion of enalaprilat (an angiotensin converting enzyme inhibitor) on responses initiated by concomitantly infused acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in the forearm arterial beds of healthy volunteers. Although the angiotensin converting enzyme inhibitor alone did not affect basal forearm blood flow or vascular resistance, it significantly augmented the increase in blood flow and reduction in vascular resistance induced by acetylcholine (both p < 0.05). Coinfusion of enalaprilat did not enhance sodium nitroprusside-induced vasodilation. Pretreatment with NG-monomethyl-L-arginine blocked the augmentation of blood flow induced by the angiotensin converting enzyme inhibitor. The effect of enalaprilat was still observed after the administration of acetylsalicylic acid (p < 0.05). These results suggest that angiotensin converting enzyme inhibitors potentiate nonprostanoid endothelium-derived relaxing factor in normal human forearm vasculature.", "contents": "Endothelium-dependent vasodilation is augmented by angiotensin converting enzyme inhibitors in healthy volunteers. We have examined the effects of local intra-arterial infusion of enalaprilat (an angiotensin converting enzyme inhibitor) on responses initiated by concomitantly infused acetylcholine (an endothelium-dependent vasodilator) and sodium nitroprusside (a direct dilator of smooth muscle) in the forearm arterial beds of healthy volunteers. Although the angiotensin converting enzyme inhibitor alone did not affect basal forearm blood flow or vascular resistance, it significantly augmented the increase in blood flow and reduction in vascular resistance induced by acetylcholine (both p < 0.05). Coinfusion of enalaprilat did not enhance sodium nitroprusside-induced vasodilation. Pretreatment with NG-monomethyl-L-arginine blocked the augmentation of blood flow induced by the angiotensin converting enzyme inhibitor. The effect of enalaprilat was still observed after the administration of acetylsalicylic acid (p < 0.05). These results suggest that angiotensin converting enzyme inhibitors potentiate nonprostanoid endothelium-derived relaxing factor in normal human forearm vasculature."} {"id": "PMID:1282599", "title": "Electrophysiologic effects of RS-2135, a new antiarrhythmic compound, on canine Purkinje fibers.", "content": "RS-2135 is the (+) isomer of a novel, fused carbazol derivative. The agent, when administered orally, shows long-lasting antiarrhythmic effects in several models of arrhythmia. We used standard microelectrode techniques to characterize the electrophysiological effects of the agent on canine Purkinje fibers. RS-2135 reduced the maximum upstroke velocity of the action potential (Vmax) and shortened the action potential duration (APD) in a concentration-related manner (0.3-3 microM). RS-2135 decreased Vmax at lower concentrations than disopyramide, flecainide, and mexiletine. RS-2135 shortened the effective refractory period (ERP), but significantly increased the ratio of ERP to APD90. Additionally, the effects of the (-) optical isomer of RS-2135 were compared with those of RS-2135, the (+) enantiomer. The (-) isomer was much less potent than RS-2135 in decreasing Vmax. These data suggest that RS-2135 belongs to the class I or \"local anesthetic\" type of antiarrhythmic agent and that the stereochemistry of the drug molecule is an important determinant of Na channel blocking activity.", "contents": "Electrophysiologic effects of RS-2135, a new antiarrhythmic compound, on canine Purkinje fibers. RS-2135 is the (+) isomer of a novel, fused carbazol derivative. The agent, when administered orally, shows long-lasting antiarrhythmic effects in several models of arrhythmia. We used standard microelectrode techniques to characterize the electrophysiological effects of the agent on canine Purkinje fibers. RS-2135 reduced the maximum upstroke velocity of the action potential (Vmax) and shortened the action potential duration (APD) in a concentration-related manner (0.3-3 microM). RS-2135 decreased Vmax at lower concentrations than disopyramide, flecainide, and mexiletine. RS-2135 shortened the effective refractory period (ERP), but significantly increased the ratio of ERP to APD90. Additionally, the effects of the (-) optical isomer of RS-2135 were compared with those of RS-2135, the (+) enantiomer. The (-) isomer was much less potent than RS-2135 in decreasing Vmax. These data suggest that RS-2135 belongs to the class I or \"local anesthetic\" type of antiarrhythmic agent and that the stereochemistry of the drug molecule is an important determinant of Na channel blocking activity."} {"id": "PMID:1282600", "title": "Cardiac microdialysis measurement of extracellular adenine nucleotide breakdown products during regional ischemia and reperfusion in canine heart: protective effect of propranolol against reperfusion injury.", "content": "Using cardiac microdialysis, we studied release of the adenine nucleotide breakdown products (ANBP) adenosine (ADS), inosine (INS), and hypoxanthine (HYP) into the interstitium of canine myocardium during 20- and 40-min occlusion of the anterior descending coronary artery and reperfusion. Dialysate ANBP concentrations reached maximum values not at the end of ischemia but in the first 10 min of reperfusion. The effect was more pronounced after 20-min ischemia. Further reperfusion led to an ANBP decrease that was more prolonged after 40-min ischemia. Pretreatment with DL-propranolol (0.5 mg/kg, intravenously, i.v.) given 40 min before coronary occlusion had no effect on adenine nucleotide catabolism rate during 20- and 40-min ischemia, but it facilitated washout of ANBP from ischemic zone immediately after the start of reperfusion. A similar effect was elicited by a D-stereoisomer of propranolol with no beta-adrenoceptor blocking activity. Results suggest that the reperfusion injury and probably the no-reflow phenomenon were the cause of enhanced adenine nucleotide catabolism at the beginning of reperfusion and prolonged ANBP washout from the ischemic zone. Reduction of reperfusion injury by propranolol could be related to the membrane stabilizing and antioxidant activity of this agent. Examination of DL-propranolol kinetics in arterial and coronary venous blood plasma showed that drug accumulation in the myocardium was almost maximum at the start of ischemia; therefore, the efficiency of cardio-protection with DL-propranolol was not limited by pharmacokinetic causes. Insertion of an additional microdialysis probe in the myocardium allowed monitoring of extracellular propranolol concentrations.", "contents": "Cardiac microdialysis measurement of extracellular adenine nucleotide breakdown products during regional ischemia and reperfusion in canine heart: protective effect of propranolol against reperfusion injury. Using cardiac microdialysis, we studied release of the adenine nucleotide breakdown products (ANBP) adenosine (ADS), inosine (INS), and hypoxanthine (HYP) into the interstitium of canine myocardium during 20- and 40-min occlusion of the anterior descending coronary artery and reperfusion. Dialysate ANBP concentrations reached maximum values not at the end of ischemia but in the first 10 min of reperfusion. The effect was more pronounced after 20-min ischemia. Further reperfusion led to an ANBP decrease that was more prolonged after 40-min ischemia. Pretreatment with DL-propranolol (0.5 mg/kg, intravenously, i.v.) given 40 min before coronary occlusion had no effect on adenine nucleotide catabolism rate during 20- and 40-min ischemia, but it facilitated washout of ANBP from ischemic zone immediately after the start of reperfusion. A similar effect was elicited by a D-stereoisomer of propranolol with no beta-adrenoceptor blocking activity. Results suggest that the reperfusion injury and probably the no-reflow phenomenon were the cause of enhanced adenine nucleotide catabolism at the beginning of reperfusion and prolonged ANBP washout from the ischemic zone. Reduction of reperfusion injury by propranolol could be related to the membrane stabilizing and antioxidant activity of this agent. Examination of DL-propranolol kinetics in arterial and coronary venous blood plasma showed that drug accumulation in the myocardium was almost maximum at the start of ischemia; therefore, the efficiency of cardio-protection with DL-propranolol was not limited by pharmacokinetic causes. Insertion of an additional microdialysis probe in the myocardium allowed monitoring of extracellular propranolol concentrations."} {"id": "PMID:1282601", "title": "Effect of cloricromene during ischemia and reperfusion of rabbit hindlimb: evidence for an involvement of leukocytes in reperfusion-mediated tissue and vascular injury.", "content": "The involvement of polymorphonuclear leukocytes (PMN) in reperfusion-mediated vascular injury was studied in a model of ischemia and reperfusion in rabbit hindlimb. Ischemia was induced by 4-h occlusion of the left iliac artery followed by 4-h reperfusion. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activities, hindlimb vascular resistance (HVR), and myeloperoxidase (MPO) activity in the postischemic extensor digitorum longus (EDL) muscle were measured to evaluate the extent of vascular and skeletal muscle injury. In addition, the ischemia/reperfusion-induced injury of the hindlimb vasculature was evaluated by electron microscopy. Ischemia and reperfusion (n = 10) was associated with an increase in CK (6,380 +/- 1,346 U/L, p < 0.05) and LDH (552 +/- 76 U/L, p < 0.05) activities which were significantly greater than those observed in sham-operated control animals (CK 1,651 +/- 207 U/L, LDH 246 +/- 14 U/L; n = 6). HVR in sham-operated animals decreased by 20 +/- 3%, but increased in the ischaemic group by 56 +/- 16% (p < 0.05). MPO activity of EDL muscle increased from 7.3 +/- 3.9 U per muscle (sham) to 28.0 +/- 5.9 U per muscle (p < 0.05) after ischemia and reperfusion. Morphologic analysis did not show any alteration in the microvascular bed of the hindlimb. Moreover, 1 mg/kg/h intravenous (i.v.) cloricromene, an antithrombotic drug that inhibits superoxide anion production as well as PMN adhesion to endothelium, reduced the increase in plasma CK and LDH and the increase in MPO and HVR observed in animals subjected to hindlimb ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effect of cloricromene during ischemia and reperfusion of rabbit hindlimb: evidence for an involvement of leukocytes in reperfusion-mediated tissue and vascular injury. The involvement of polymorphonuclear leukocytes (PMN) in reperfusion-mediated vascular injury was studied in a model of ischemia and reperfusion in rabbit hindlimb. Ischemia was induced by 4-h occlusion of the left iliac artery followed by 4-h reperfusion. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activities, hindlimb vascular resistance (HVR), and myeloperoxidase (MPO) activity in the postischemic extensor digitorum longus (EDL) muscle were measured to evaluate the extent of vascular and skeletal muscle injury. In addition, the ischemia/reperfusion-induced injury of the hindlimb vasculature was evaluated by electron microscopy. Ischemia and reperfusion (n = 10) was associated with an increase in CK (6,380 +/- 1,346 U/L, p < 0.05) and LDH (552 +/- 76 U/L, p < 0.05) activities which were significantly greater than those observed in sham-operated control animals (CK 1,651 +/- 207 U/L, LDH 246 +/- 14 U/L; n = 6). HVR in sham-operated animals decreased by 20 +/- 3%, but increased in the ischaemic group by 56 +/- 16% (p < 0.05). MPO activity of EDL muscle increased from 7.3 +/- 3.9 U per muscle (sham) to 28.0 +/- 5.9 U per muscle (p < 0.05) after ischemia and reperfusion. Morphologic analysis did not show any alteration in the microvascular bed of the hindlimb. Moreover, 1 mg/kg/h intravenous (i.v.) cloricromene, an antithrombotic drug that inhibits superoxide anion production as well as PMN adhesion to endothelium, reduced the increase in plasma CK and LDH and the increase in MPO and HVR observed in animals subjected to hindlimb ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282602", "title": "Differential effect of selective beta 1 and nonselective beta-adrenoceptor blockade on epinephrine and atropine response in normal humans.", "content": "Sympathetic stimulation with epinephrine (EPI) combined with parasympathetic blockade with atropine was studied in 10 healthy volunteers premedicated with placebo or three different beta-adrenoceptor blockers: atenolol (62.5 micrograms/kg, beta 1-selective), propranolol (62.5 micrograms/kg, nonselective), and pindolol (7.5 micrograms/kg, nonselective with intrinsic sympathomimetic activity, ISA). EPI infusion (0.06 microgram/kg/min) after placebo increased heart rate (HR) and systolic blood pressure (SBP) and decreased diastolic BP (DBP). Pretreatment with atenolol reduced the HR increase, and caused similar changes in BP. In contrast, pretreatment with propranolol and pindolol decreased HR and increased BP. Combined EPI and atropine (15 micrograms/kg) after placebo increased HR by 40% without causing BP changes. Similar HR changes were observed after administration of all beta-adrenoceptor blockers, but whereas a marked pressor response was observed after propranolol and pindolol a blunted response was observed after atenolol. Propranolol and pindolol reduced myocardial oxygen demand estimated by the HR x BP product after EPI, but this response was abolished by atropine. Serum potassium decreased from 3.9 +/- 0.2 to 3.2 +/- 0.3 mM after EPi and atropine. This effect was less after atenolol, and potassium increased after premedication with propranolol and pindolol. Our results show that nonselective beta-adrenoceptor blockade has a favorable effect on potassium homeostasis and oxygen demand parameters during EPI infusion but causes a marked pressor response, contrary to a beta 1-selective agent, during combined sympathetic stimulation and parasympathetic blockade. They also highlight the importance of the vasodilator cholinergic system as a defense mechanism in such situations.", "contents": "Differential effect of selective beta 1 and nonselective beta-adrenoceptor blockade on epinephrine and atropine response in normal humans. Sympathetic stimulation with epinephrine (EPI) combined with parasympathetic blockade with atropine was studied in 10 healthy volunteers premedicated with placebo or three different beta-adrenoceptor blockers: atenolol (62.5 micrograms/kg, beta 1-selective), propranolol (62.5 micrograms/kg, nonselective), and pindolol (7.5 micrograms/kg, nonselective with intrinsic sympathomimetic activity, ISA). EPI infusion (0.06 microgram/kg/min) after placebo increased heart rate (HR) and systolic blood pressure (SBP) and decreased diastolic BP (DBP). Pretreatment with atenolol reduced the HR increase, and caused similar changes in BP. In contrast, pretreatment with propranolol and pindolol decreased HR and increased BP. Combined EPI and atropine (15 micrograms/kg) after placebo increased HR by 40% without causing BP changes. Similar HR changes were observed after administration of all beta-adrenoceptor blockers, but whereas a marked pressor response was observed after propranolol and pindolol a blunted response was observed after atenolol. Propranolol and pindolol reduced myocardial oxygen demand estimated by the HR x BP product after EPI, but this response was abolished by atropine. Serum potassium decreased from 3.9 +/- 0.2 to 3.2 +/- 0.3 mM after EPi and atropine. This effect was less after atenolol, and potassium increased after premedication with propranolol and pindolol. Our results show that nonselective beta-adrenoceptor blockade has a favorable effect on potassium homeostasis and oxygen demand parameters during EPI infusion but causes a marked pressor response, contrary to a beta 1-selective agent, during combined sympathetic stimulation and parasympathetic blockade. They also highlight the importance of the vasodilator cholinergic system as a defense mechanism in such situations."} {"id": "PMID:1282603", "title": "Prolonged activation of alpha 1 adrenoceptors induces down-regulation of protein kinase C in vascular smooth muscle.", "content": "Sustained exposure of vascular smooth muscle to catecholamines results in desensitization of alpha 1-adrenoreceptor-mediated vascular smooth muscle contraction. The present study was designed to determine the effects of prolonged exposure of blood vessels to catecholamines on protein kinase C (PKC) activity. Incubation of rat aortic smooth muscle with 10 microM norepinephrine (NE) for 4 h resulted in a threefold decrease in sensitivity of the contractile response of rat aortic smooth muscle to the phorbol ester 4 beta-phorbol 12,13-dibutyrate (PDBu); this loss in sensitivity was dependent on the presence of endothelium. NE induced a 45% decrease in enzymatic activity of the soluble and particulate forms of PKC. With [3H]PDBu used to label phorbol ester receptor binding sites in the aorta, there was a 34% decrease in [3H]PDBu binding sites in NE-treated blood vessels without change in binding affinity for the ligand. To determine whether this loss in enzymatic activity and [3H]PDBu binding resulted from a decrease in the quantity of the enzyme, Western blot analyses were performed using a monoclonal antibody (MoAb) against PKC. This approach confirmed the presence of an 80-Kd immunoreactive PKC in the soluble fraction of rat aortic smooth muscle and demonstrated a 44% decrease in the amount of PKC in blood vessels after sustained exposure to catecholamines. Our results demonstrate that prolonged activation of alpha-adrenoceptors in blood vessels leads to down-regulation of PKC which may contribute to desensitization of contraction mediated by vasoconstrictors.", "contents": "Prolonged activation of alpha 1 adrenoceptors induces down-regulation of protein kinase C in vascular smooth muscle. Sustained exposure of vascular smooth muscle to catecholamines results in desensitization of alpha 1-adrenoreceptor-mediated vascular smooth muscle contraction. The present study was designed to determine the effects of prolonged exposure of blood vessels to catecholamines on protein kinase C (PKC) activity. Incubation of rat aortic smooth muscle with 10 microM norepinephrine (NE) for 4 h resulted in a threefold decrease in sensitivity of the contractile response of rat aortic smooth muscle to the phorbol ester 4 beta-phorbol 12,13-dibutyrate (PDBu); this loss in sensitivity was dependent on the presence of endothelium. NE induced a 45% decrease in enzymatic activity of the soluble and particulate forms of PKC. With [3H]PDBu used to label phorbol ester receptor binding sites in the aorta, there was a 34% decrease in [3H]PDBu binding sites in NE-treated blood vessels without change in binding affinity for the ligand. To determine whether this loss in enzymatic activity and [3H]PDBu binding resulted from a decrease in the quantity of the enzyme, Western blot analyses were performed using a monoclonal antibody (MoAb) against PKC. This approach confirmed the presence of an 80-Kd immunoreactive PKC in the soluble fraction of rat aortic smooth muscle and demonstrated a 44% decrease in the amount of PKC in blood vessels after sustained exposure to catecholamines. Our results demonstrate that prolonged activation of alpha-adrenoceptors in blood vessels leads to down-regulation of PKC which may contribute to desensitization of contraction mediated by vasoconstrictors."} {"id": "PMID:1282604", "title": "Effect of beta-adrenergic receptor antagonism on chloralose-induced hemodynamic changes in newborn lambs.", "content": "alpha-Chloralose is an anesthetic commonly used in cardiovascular research. Using a chronically instrumented neonatal lamb model, we previously determined that chloralose has important effects on basal hemodynamics and arterial oxygen tension as compared with those of paired conscious control lambs. We wished to determine whether beta-adrenergic receptor stimulation accounted for chloralose-induced hemodynamic effects and to investigate the influence of chloralose and beta-adrenergic receptor antagonism on oxygen metabolism. In paired studies, five lambs were given chloralose intravenously (30 mg/kg i.v.) after propranolol (1 mg/kg i.v.) or saline control. The group pretreated with propranolol had reduced heart rate (HR 206 +/- 12 vs. 244 +/- 10 beats/min, p = 0.04) and cardiac output (CO 253 +/- 29 vs. 302 +/- 40 ml/min/kg, p = 0.005) 30 min after chloralose as compared with control; pretreatment with propranolol also attenuated the systemic hypertensive response to chloralose (77 +/- 8 vs. 89 +/- 5 mm Hg, p = 0.055). No difference in the response of stroke volume (SV), atrial or pulmonary arterial pressures, or pulmonary and systemic vascular resistances (PVR, SVR) were observed between treatment groups. No differences between propranolol and saline treatment groups were observed in arterial and mixed venous oxygen contents, arteriovenous (A-V) oxygen difference, oxygen extraction, or oxygen consumption; a reduction in oxygen delivery observed after propranolol as compared with saline was not altered by chloralose. We conclude that tachycardia and increase in CO induced by chloralose in lambs probably are mediated by beta-adrenergic receptor stimulation, which may be direct or indirect.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effect of beta-adrenergic receptor antagonism on chloralose-induced hemodynamic changes in newborn lambs. alpha-Chloralose is an anesthetic commonly used in cardiovascular research. Using a chronically instrumented neonatal lamb model, we previously determined that chloralose has important effects on basal hemodynamics and arterial oxygen tension as compared with those of paired conscious control lambs. We wished to determine whether beta-adrenergic receptor stimulation accounted for chloralose-induced hemodynamic effects and to investigate the influence of chloralose and beta-adrenergic receptor antagonism on oxygen metabolism. In paired studies, five lambs were given chloralose intravenously (30 mg/kg i.v.) after propranolol (1 mg/kg i.v.) or saline control. The group pretreated with propranolol had reduced heart rate (HR 206 +/- 12 vs. 244 +/- 10 beats/min, p = 0.04) and cardiac output (CO 253 +/- 29 vs. 302 +/- 40 ml/min/kg, p = 0.005) 30 min after chloralose as compared with control; pretreatment with propranolol also attenuated the systemic hypertensive response to chloralose (77 +/- 8 vs. 89 +/- 5 mm Hg, p = 0.055). No difference in the response of stroke volume (SV), atrial or pulmonary arterial pressures, or pulmonary and systemic vascular resistances (PVR, SVR) were observed between treatment groups. No differences between propranolol and saline treatment groups were observed in arterial and mixed venous oxygen contents, arteriovenous (A-V) oxygen difference, oxygen extraction, or oxygen consumption; a reduction in oxygen delivery observed after propranolol as compared with saline was not altered by chloralose. We conclude that tachycardia and increase in CO induced by chloralose in lambs probably are mediated by beta-adrenergic receptor stimulation, which may be direct or indirect.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282605", "title": "Inhibition of platelet-activating factor fails to limit ischemia and reperfusion-induced myocardial damage.", "content": "To determine the role of platelet-activating factor (1-O-hexa-decyl-2-acetyl-sn-glyceryl-phosphoryl-choline, PAF) in myocardial ischemic and reperfusion-induced injury, the effects of a PAF receptor antagonist (WEB 2086) were studied in an anesthetized canine model of ischemia (90 min) and reperfusion (6 h). Thirty minutes after onset of ischemia, WEB 2086 was administered as a bolus (20 mg/kg intravenously, i.v.) followed by a continuous 6-h infusion (10 mg/kg/h i.v.). Controls received vehicle alone (0.9% saline). Platelet aggregation was studied at baseline and at 1, 2, 4, and 6 h of drug administration and at the end of the reperfusion period. WEB 2086 treatment did not significantly affect platelet aggregation stimulated by ADP or arachidonic acid (AA). After 1 h of drug infusion, the ex vivo aggregatory response to exogenous (200 nM) PAF was ablated in WEB 2086-treated animals. WEB 2086 administration did not affect heart rate (HR) or mean arterial blood pressure (MAP) during the occlusion or reperfusion phases. During reperfusion of the ischemic tissue, left circumflex coronary artery (LCX) blood flow of WEB 2086-treated animals increased (p < 0.05) above control value. The area of the left ventricle at risk of infarct was not different between control and WEB 2086-treated groups. Infarct size was not significantly reduced in WEB 2086-treated animals. The results of our investigation using a 90-min ischemic period followed by 6-h reperfusion show that pharmacologic antagonism of PAF by WEB 2086 does not protect the heart against ischemia and reperfusion-induced injury.", "contents": "Inhibition of platelet-activating factor fails to limit ischemia and reperfusion-induced myocardial damage. To determine the role of platelet-activating factor (1-O-hexa-decyl-2-acetyl-sn-glyceryl-phosphoryl-choline, PAF) in myocardial ischemic and reperfusion-induced injury, the effects of a PAF receptor antagonist (WEB 2086) were studied in an anesthetized canine model of ischemia (90 min) and reperfusion (6 h). Thirty minutes after onset of ischemia, WEB 2086 was administered as a bolus (20 mg/kg intravenously, i.v.) followed by a continuous 6-h infusion (10 mg/kg/h i.v.). Controls received vehicle alone (0.9% saline). Platelet aggregation was studied at baseline and at 1, 2, 4, and 6 h of drug administration and at the end of the reperfusion period. WEB 2086 treatment did not significantly affect platelet aggregation stimulated by ADP or arachidonic acid (AA). After 1 h of drug infusion, the ex vivo aggregatory response to exogenous (200 nM) PAF was ablated in WEB 2086-treated animals. WEB 2086 administration did not affect heart rate (HR) or mean arterial blood pressure (MAP) during the occlusion or reperfusion phases. During reperfusion of the ischemic tissue, left circumflex coronary artery (LCX) blood flow of WEB 2086-treated animals increased (p < 0.05) above control value. The area of the left ventricle at risk of infarct was not different between control and WEB 2086-treated groups. Infarct size was not significantly reduced in WEB 2086-treated animals. The results of our investigation using a 90-min ischemic period followed by 6-h reperfusion show that pharmacologic antagonism of PAF by WEB 2086 does not protect the heart against ischemia and reperfusion-induced injury."} {"id": "PMID:1282606", "title": "Postischemic stunning: the two-phase model for the role of calcium as pathogen.", "content": "The hypothesis proposed is that postischemic stunning occurs in two phases. The first and causative phase occurs very rapidly after the onset of reperfusion and is associated with cytosolic calcium overload with transiently normal mechanical function. If agents enhancing calcium influx are given at this early stage, they worsen subsequent stunning. Conversely, agents inhibiting calcium influx such as nisoldipine may lessen the extent of stunning. In the second phase (established stunning), there is hypocontractility and calcium antagonists given to isolated hearts can further impair mechanical function. Logically, agents enhancing calcium influx improve mechanical function. Unexpectedly, calcium antagonists given to large animal hearts in situ can improve established stunning, through mechanisms that are not well understood. The harmful effects of free radicals are not discounted but can be explained by early membrane damage with a consequent rise in cytosolic calcium during the early first phase of reperfusion.", "contents": "Postischemic stunning: the two-phase model for the role of calcium as pathogen. The hypothesis proposed is that postischemic stunning occurs in two phases. The first and causative phase occurs very rapidly after the onset of reperfusion and is associated with cytosolic calcium overload with transiently normal mechanical function. If agents enhancing calcium influx are given at this early stage, they worsen subsequent stunning. Conversely, agents inhibiting calcium influx such as nisoldipine may lessen the extent of stunning. In the second phase (established stunning), there is hypocontractility and calcium antagonists given to isolated hearts can further impair mechanical function. Logically, agents enhancing calcium influx improve mechanical function. Unexpectedly, calcium antagonists given to large animal hearts in situ can improve established stunning, through mechanisms that are not well understood. The harmful effects of free radicals are not discounted but can be explained by early membrane damage with a consequent rise in cytosolic calcium during the early first phase of reperfusion."} {"id": "PMID:1282608", "title": "The role of oxygen radicals during reperfusion.", "content": "Oxy and hydroxy radicals produced during postischemic reperfusion may contribute to the mechanisms responsible for the sustained contractile dysfunction and ultrastructural injury that occur under these conditions. At the molecular level, the consequent peroxidation of membrane-located lipids (including membranes that delineate the sarcoplasmic reticulum, the mitochondria, and the myocytes) probably contributes to the associated loss of Ca2+ homeostasis. Protection against oxy and hydroxy radical-induced injury can be approached in several ways. Oxy and hydroxy radical formation can be limited, or the radicals \"trapped.\" Alternatively, agents that protect membranes against lipid peroxidation-induced injury can be used. To determine whether the calcium antagonist nisoldipine has such a protective effect, isolated hearts were exposed to 0.9 mM H2O2 for short periods of time, and the functional recovery on removal of the H2O2 was used to assess the protective effect of 5 x 10(-9) M nisoldipine. In addition, further evidence of protection was obtained by exposing hearts to an oxy radical-generating system in the presence and absence of 10(-8) M nisoldipine and using the inhibitory effect of nisoldipine on the oxy radical-induced externalization of the endothelin-1 ETA binding sites to quantify protection.", "contents": "The role of oxygen radicals during reperfusion. Oxy and hydroxy radicals produced during postischemic reperfusion may contribute to the mechanisms responsible for the sustained contractile dysfunction and ultrastructural injury that occur under these conditions. At the molecular level, the consequent peroxidation of membrane-located lipids (including membranes that delineate the sarcoplasmic reticulum, the mitochondria, and the myocytes) probably contributes to the associated loss of Ca2+ homeostasis. Protection against oxy and hydroxy radical-induced injury can be approached in several ways. Oxy and hydroxy radical formation can be limited, or the radicals \"trapped.\" Alternatively, agents that protect membranes against lipid peroxidation-induced injury can be used. To determine whether the calcium antagonist nisoldipine has such a protective effect, isolated hearts were exposed to 0.9 mM H2O2 for short periods of time, and the functional recovery on removal of the H2O2 was used to assess the protective effect of 5 x 10(-9) M nisoldipine. In addition, further evidence of protection was obtained by exposing hearts to an oxy radical-generating system in the presence and absence of 10(-8) M nisoldipine and using the inhibitory effect of nisoldipine on the oxy radical-induced externalization of the endothelin-1 ETA binding sites to quantify protection."} {"id": "PMID:1282609", "title": "Myocardial stunning following coronary angioplasty: protective effects of calcium-channel blockers.", "content": "The beneficial effects of calcium-channel blockers against myocardial stunning have been tested in experimental studies, showing that, when added before or during ischemia, a protective effect against postischemia stunning is achieved. The present study was undertaken to test and compare the protective effect of calcium antagonists [nisoldipine (NIS) and nifedipine (NIF)] and nitrates (NIT) against myocardial stunning in patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) with prolonged inflation as PTCA represents a model of induced acute and severe ischemia for a brief period and might cause myocardial stunning. The study included 30 patients between the ages of 42 and 67 years, all with exercise-induced angina and single-vessel disease, with severe stenosis (80% to subtotal occlusion) localized on the left anterior descending artery and with the absence of collaterals on the coronary angiograms. Moreover, all patients had normal left ventricular (LV) overall function, as well as normal systolic thickening of the anterior wall, supplied by the diseased artery. Patients were randomized to a pre-PTCA treatment with NIT, 80-120 mg/day (10 patients), NIF, 40-60 mg/day (10 patients), and NIS, 10-20 mg/day (10 patients). Pre-PTCA treatment was initiated 7 days before the procedure and continued after. During the PTCA, at the first balloon inflation, an additional dose of 300 micrograms of NIT was injected into the left anterior descending artery through the balloon catheter in the patients in the NIT group, as well as 0.2 mg of NIF in NIF group patients and 0.05 mg of NIS in NIS group patients.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Myocardial stunning following coronary angioplasty: protective effects of calcium-channel blockers. The beneficial effects of calcium-channel blockers against myocardial stunning have been tested in experimental studies, showing that, when added before or during ischemia, a protective effect against postischemia stunning is achieved. The present study was undertaken to test and compare the protective effect of calcium antagonists [nisoldipine (NIS) and nifedipine (NIF)] and nitrates (NIT) against myocardial stunning in patients with coronary artery disease undergoing percutaneous transluminal coronary angioplasty (PTCA) with prolonged inflation as PTCA represents a model of induced acute and severe ischemia for a brief period and might cause myocardial stunning. The study included 30 patients between the ages of 42 and 67 years, all with exercise-induced angina and single-vessel disease, with severe stenosis (80% to subtotal occlusion) localized on the left anterior descending artery and with the absence of collaterals on the coronary angiograms. Moreover, all patients had normal left ventricular (LV) overall function, as well as normal systolic thickening of the anterior wall, supplied by the diseased artery. Patients were randomized to a pre-PTCA treatment with NIT, 80-120 mg/day (10 patients), NIF, 40-60 mg/day (10 patients), and NIS, 10-20 mg/day (10 patients). Pre-PTCA treatment was initiated 7 days before the procedure and continued after. During the PTCA, at the first balloon inflation, an additional dose of 300 micrograms of NIT was injected into the left anterior descending artery through the balloon catheter in the patients in the NIT group, as well as 0.2 mg of NIF in NIF group patients and 0.05 mg of NIS in NIS group patients.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282610", "title": "Characterization of \"hibernating\" and \"stunned\" myocardium with focus on the use of calcium antagonists in \"stunned\" myocardium.", "content": "In the initial seconds after a sudden reduction in coronary blood flow, a temporary mismatch between myocardial energy demand and supply exists. The mechanisms underlying the rapidly ensuing reduction in contractile function in the ischemic myocardium are still unknown. In the presence of some residual blood flow, a state of \"perfusion-contraction matching\" develops. The metabolic status of such hypoperfused myocardium improves, since myocardial lactate production is attenuated and creatine phosphate (CP), after an initial reduction, returns toward control values. The hypoperfused myocardium responds to inotropic stimulation by dobutamine. The recruitment of an inotropic reserve implies increased energy utilization. During inotropic stimulation, after partial normalization, lactate production is again increased, and CP is decreased again. Thus, a supply-demand imbalance that had been at least partially corrected by the ischemia-induced decrease in regional contractile function is precipitated again. A situation of chronic contractile failure in viable myocardium that normalizes upon reperfusion has been termed myocardial \"hibernation.\" Myocardial \"stunning\" is characterized by a reversible postischemic contractile dysfunction despite full restoration of blood flow. The details of the underlying mechanisms are not clear. An inadequate energy supply and impaired sympathetic neurotransmission have been excluded. Potential mechanisms, which are not mutually exclusive, may include (a) damage of membranes by free radicals, (b) an increase in free cytosolic calcium during ischemia and reperfusion, and (c) a decrease in the calcium sensitivity of the myofibrils. The equally pronounced increases in regional contractility in normal and \"stunned\" myocardium during postextrasystolic potentiation and the infusion of calcium or the calcium-sensitizing agent AR-L-57, however, suggest an unchanged calcium sensitivity of reperfused myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Characterization of \"hibernating\" and \"stunned\" myocardium with focus on the use of calcium antagonists in \"stunned\" myocardium. In the initial seconds after a sudden reduction in coronary blood flow, a temporary mismatch between myocardial energy demand and supply exists. The mechanisms underlying the rapidly ensuing reduction in contractile function in the ischemic myocardium are still unknown. In the presence of some residual blood flow, a state of \"perfusion-contraction matching\" develops. The metabolic status of such hypoperfused myocardium improves, since myocardial lactate production is attenuated and creatine phosphate (CP), after an initial reduction, returns toward control values. The hypoperfused myocardium responds to inotropic stimulation by dobutamine. The recruitment of an inotropic reserve implies increased energy utilization. During inotropic stimulation, after partial normalization, lactate production is again increased, and CP is decreased again. Thus, a supply-demand imbalance that had been at least partially corrected by the ischemia-induced decrease in regional contractile function is precipitated again. A situation of chronic contractile failure in viable myocardium that normalizes upon reperfusion has been termed myocardial \"hibernation.\" Myocardial \"stunning\" is characterized by a reversible postischemic contractile dysfunction despite full restoration of blood flow. The details of the underlying mechanisms are not clear. An inadequate energy supply and impaired sympathetic neurotransmission have been excluded. Potential mechanisms, which are not mutually exclusive, may include (a) damage of membranes by free radicals, (b) an increase in free cytosolic calcium during ischemia and reperfusion, and (c) a decrease in the calcium sensitivity of the myofibrils. The equally pronounced increases in regional contractility in normal and \"stunned\" myocardium during postextrasystolic potentiation and the infusion of calcium or the calcium-sensitizing agent AR-L-57, however, suggest an unchanged calcium sensitivity of reperfused myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282611", "title": "Selectivity scale of calcium antagonists in the human cardiovascular system based on in vitro studies.", "content": "The inhibitory effect of calcium antagonists has been studied on the calcium signal and on contractile activity in the human coronary and internal mammary arteries. We observed that rhythmic vasospasms, either spontaneous or evoked by serotonin and endothelin, were highly sensitive to calcium-channel inhibitors. Functional parameters describing the inhibition have been compared to binding parameters estimated in radioligand studies on membranes prepared from human coronary artery and from human heart. Taking the present studies and observations already published together, it was possible to build up a selectivity scale for diltiazem, verapamil, nifedipine, and nisoldipine. This showed that nisoldipine was more selective for coronary artery than the other calcium antagonists so far studied. Such a selectivity observed in functional studies on intact human preparations in vitro could be predicted considering the kinetic parameters of the interaction of nisoldipine with calcium channels.", "contents": "Selectivity scale of calcium antagonists in the human cardiovascular system based on in vitro studies. The inhibitory effect of calcium antagonists has been studied on the calcium signal and on contractile activity in the human coronary and internal mammary arteries. We observed that rhythmic vasospasms, either spontaneous or evoked by serotonin and endothelin, were highly sensitive to calcium-channel inhibitors. Functional parameters describing the inhibition have been compared to binding parameters estimated in radioligand studies on membranes prepared from human coronary artery and from human heart. Taking the present studies and observations already published together, it was possible to build up a selectivity scale for diltiazem, verapamil, nifedipine, and nisoldipine. This showed that nisoldipine was more selective for coronary artery than the other calcium antagonists so far studied. Such a selectivity observed in functional studies on intact human preparations in vitro could be predicted considering the kinetic parameters of the interaction of nisoldipine with calcium channels."} {"id": "PMID:1282612", "title": "Ventricular function and calcium handling during ischemia.", "content": "Ischemia-induced ventricular dysfunction has been shown to be associated with increased diastolic and systolic intracellular concentrations of free, ionized calcium ([CA2+]i). The present study was designed to determine the effects of the calcium antagonist nisoldipine on the relationship between [Ca2+]i and left ventricular contraction and relaxation during ischemia and reperfusion on a beat-to-beat basis. Nine isovolumic coronary-perfused ferret hearts were made globally ischemic for 3 min and reperfused for 10 min. Ischemia and reperfusion were repeated during perfusion with buffer containing 10(-8) M nisoldipine. From the left ventricular developed pressure, the time to peak pressure and time to 50% pressure decline were obtained. [Ca2+]i was determined with the bioluminescent protein aequorin. Global ischemia caused a rapid decline in contractile function and a significant increase in diastolic [Ca2+]i from 0.35 to 0.81 microM and in systolic [Ca2+]i, from 0.61 to 0.96 microM. During reperfusion, [Ca2+]i returned to baseline while ventricular function was still impaired. Relaxation was more affected than systolic contractile function (Fig. 1). Nisoldipine significantly reduced the ischemia-induced rise in diastolic [Ca2+]i to 0.62 microM and in systolic [Ca2+]i to 0.77 microM and lessened the decrease in contractile function. Nisoldipine significantly accelerated the decline in [Ca2+]i during reperfusion and improved recovery of contractility and relaxation. These effects were associated with a significant diminution in ischemic lactate production. Taken together, our results provide direct quantitative evidence on a beat-to-beat basis that the calcium antagonist nisoldipine can ameliorate ischemia-induced abnormalities in [Ca2+]i handling, an effect that was associated with improved myocardial function during early reperfusion.", "contents": "Ventricular function and calcium handling during ischemia. Ischemia-induced ventricular dysfunction has been shown to be associated with increased diastolic and systolic intracellular concentrations of free, ionized calcium ([CA2+]i). The present study was designed to determine the effects of the calcium antagonist nisoldipine on the relationship between [Ca2+]i and left ventricular contraction and relaxation during ischemia and reperfusion on a beat-to-beat basis. Nine isovolumic coronary-perfused ferret hearts were made globally ischemic for 3 min and reperfused for 10 min. Ischemia and reperfusion were repeated during perfusion with buffer containing 10(-8) M nisoldipine. From the left ventricular developed pressure, the time to peak pressure and time to 50% pressure decline were obtained. [Ca2+]i was determined with the bioluminescent protein aequorin. Global ischemia caused a rapid decline in contractile function and a significant increase in diastolic [Ca2+]i from 0.35 to 0.81 microM and in systolic [Ca2+]i, from 0.61 to 0.96 microM. During reperfusion, [Ca2+]i returned to baseline while ventricular function was still impaired. Relaxation was more affected than systolic contractile function (Fig. 1). Nisoldipine significantly reduced the ischemia-induced rise in diastolic [Ca2+]i to 0.62 microM and in systolic [Ca2+]i to 0.77 microM and lessened the decrease in contractile function. Nisoldipine significantly accelerated the decline in [Ca2+]i during reperfusion and improved recovery of contractility and relaxation. These effects were associated with a significant diminution in ischemic lactate production. Taken together, our results provide direct quantitative evidence on a beat-to-beat basis that the calcium antagonist nisoldipine can ameliorate ischemia-induced abnormalities in [Ca2+]i handling, an effect that was associated with improved myocardial function during early reperfusion."} {"id": "PMID:1282613", "title": "Specific coronary hemodynamic effects of nisoldipine and other vasoactive drugs.", "content": "The specific coronary hemodynamic effects of different vasoactive drugs were studied using a randomized, double-blind protocol in the \"normal\" contralateral artery after performing single-vessel coronary angioplasty. The intracoronary administration of 50 micrograms of nisoldipine resulted in an increase in epicardial diameter (+19%; p = 0.0001) and in coronary blood flow (+47%; p = 0.003), but the flow reserve decreased (-20%; p = 0.001). In placebo-treated patients, all parameters proved to be very stable and no significant changes were found. In a second study, 500 micrograms of diltiazem i.c. was administered to 20 patients, who were first randomized to pretreatment with either placebo (n = 10) or isosorbide dinitrate (0.5 micrograms/kg/min infusion; n = 10). There were increases in epicardial diameter (+10%; p = 0.0001) and coronary flow (+30%; p = 0.0001) in all patients. These changes were comparable in patients pretreated with placebo or nitrates but the reduction in coronary flow reserve was only significant in patients pretreated with placebo (+19%; p = 0.0008). In a third study, the hemodynamic effects of the intracoronary application of SIN-1 (500 micrograms), the active metabolite of molsidomine, were studied. There was a consistent increase in epicardial diameter (+26%; p < 0.0001) but the response at the microvascular level was heterogeneous and characterized by a trend to increased blood flow (+25%; p = 0.11) and decreased coronary vascular resistance (-18%; p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Specific coronary hemodynamic effects of nisoldipine and other vasoactive drugs. The specific coronary hemodynamic effects of different vasoactive drugs were studied using a randomized, double-blind protocol in the \"normal\" contralateral artery after performing single-vessel coronary angioplasty. The intracoronary administration of 50 micrograms of nisoldipine resulted in an increase in epicardial diameter (+19%; p = 0.0001) and in coronary blood flow (+47%; p = 0.003), but the flow reserve decreased (-20%; p = 0.001). In placebo-treated patients, all parameters proved to be very stable and no significant changes were found. In a second study, 500 micrograms of diltiazem i.c. was administered to 20 patients, who were first randomized to pretreatment with either placebo (n = 10) or isosorbide dinitrate (0.5 micrograms/kg/min infusion; n = 10). There were increases in epicardial diameter (+10%; p = 0.0001) and coronary flow (+30%; p = 0.0001) in all patients. These changes were comparable in patients pretreated with placebo or nitrates but the reduction in coronary flow reserve was only significant in patients pretreated with placebo (+19%; p = 0.0008). In a third study, the hemodynamic effects of the intracoronary application of SIN-1 (500 micrograms), the active metabolite of molsidomine, were studied. There was a consistent increase in epicardial diameter (+26%; p < 0.0001) but the response at the microvascular level was heterogeneous and characterized by a trend to increased blood flow (+25%; p = 0.11) and decreased coronary vascular resistance (-18%; p = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282614", "title": "Stunned and hibernating myocardium: possibility of intervention.", "content": "There are several potential outcomes of myocardial ischemia. When ischemia is severe and prolonged, irreversible damage occurs and there is no recovery of contractile function. When myocardial ischemia is less severe but still prolonged, myocytes may remain viable but exhibit depressed contractile function. Under these conditions, reperfusion restores complete contractile performance. This type of ischemia, leading to a reversible, chronic left ventricular dysfunction, has been termed hibernating myocardium. The difference between this condition and that described before, i.e., prolonged ischemia, which results in further damage on reperfusion, is, most likely, related to residual coronary flow. In the hibernating myocardium, which is always supplied by a narrow coronary artery, blood flow is not low enough to cause progression toward tissue necrosis, but it is low enough to cause pH changes that, in turn, are responsible for the downregulation of myocardial contractility. The level of underperfusion is sufficient to maintain aerobic metabolism of the quiescient myocardium as demonstrated by the absence of lactate and creatine phosphokinase release. There are no doubts that revascularization is essential for hibernated myocardium, and the clinical goal to achieve is the possibility of accurately distinguishing viable from infarcted tissue. A third possible outcome of myocardial ischemia is a postischemic ventricular dysfunction or myocardial stunning. This term describes a transient mechanical dysfunction that persists on reperfusion after a short period of ischemia, despite the absence of irreversible damage. There are numerous clinical conditions in which stunning might manifest.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Stunned and hibernating myocardium: possibility of intervention. There are several potential outcomes of myocardial ischemia. When ischemia is severe and prolonged, irreversible damage occurs and there is no recovery of contractile function. When myocardial ischemia is less severe but still prolonged, myocytes may remain viable but exhibit depressed contractile function. Under these conditions, reperfusion restores complete contractile performance. This type of ischemia, leading to a reversible, chronic left ventricular dysfunction, has been termed hibernating myocardium. The difference between this condition and that described before, i.e., prolonged ischemia, which results in further damage on reperfusion, is, most likely, related to residual coronary flow. In the hibernating myocardium, which is always supplied by a narrow coronary artery, blood flow is not low enough to cause progression toward tissue necrosis, but it is low enough to cause pH changes that, in turn, are responsible for the downregulation of myocardial contractility. The level of underperfusion is sufficient to maintain aerobic metabolism of the quiescient myocardium as demonstrated by the absence of lactate and creatine phosphokinase release. There are no doubts that revascularization is essential for hibernated myocardium, and the clinical goal to achieve is the possibility of accurately distinguishing viable from infarcted tissue. A third possible outcome of myocardial ischemia is a postischemic ventricular dysfunction or myocardial stunning. This term describes a transient mechanical dysfunction that persists on reperfusion after a short period of ischemia, despite the absence of irreversible damage. There are numerous clinical conditions in which stunning might manifest.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282615", "title": "Effects of calcium antagonists in patients with coronary disease and heart failure: left ventricular function following nisoldipine measured by radionuclide ventriculography.", "content": "Thirty-two patients with chronic heart failure were investigated with radionuclide ventriculography at rest and during exercise. The global ejection fraction (EF), ejection rate, ejection time, and filling rate were measured. The patients were subdivided into three subgroups: patients with extremely (< 25%), moderately (25-33%), and mildly decreased EF (33-40%). All patients were investigated by thallium-201 myocardial scintigraphy and the correlation between ejection parameters and infarct size was investigated. In a random protocol 17 patients (14 men, 3 women, mean age of 54.6 years) received beta-acetyldigoxin at a dose of 0.3 mg daily over 4 weeks, 15 patients (13 men, 2 women, mean age of 58.2 years) received nisoldipine at a dose of 20 mg daily. Patients on digitalis showed a further lowering of the extremely decreased EF (-1%), but in patients with moderately decreased EF, digoxin produced a marked increase in EF of +8% (p < 0.001). In mildly decreased EF, there was no significant change (+0.3%, n.s.). Nisoldipine produced an increase in pump function (+2%) in the group with extremely decreased EF up to 9% in some individual cases. A significant increase (+5%) was achieved in moderately decreased EF, while patients with mildly decreased EF did not respond. Thus, nisoldipine may be indicated in the treatment of heart failure after repeated myocardial infarctions, in particular in patients with severely decreased ejection fraction.", "contents": "Effects of calcium antagonists in patients with coronary disease and heart failure: left ventricular function following nisoldipine measured by radionuclide ventriculography. Thirty-two patients with chronic heart failure were investigated with radionuclide ventriculography at rest and during exercise. The global ejection fraction (EF), ejection rate, ejection time, and filling rate were measured. The patients were subdivided into three subgroups: patients with extremely (< 25%), moderately (25-33%), and mildly decreased EF (33-40%). All patients were investigated by thallium-201 myocardial scintigraphy and the correlation between ejection parameters and infarct size was investigated. In a random protocol 17 patients (14 men, 3 women, mean age of 54.6 years) received beta-acetyldigoxin at a dose of 0.3 mg daily over 4 weeks, 15 patients (13 men, 2 women, mean age of 58.2 years) received nisoldipine at a dose of 20 mg daily. Patients on digitalis showed a further lowering of the extremely decreased EF (-1%), but in patients with moderately decreased EF, digoxin produced a marked increase in EF of +8% (p < 0.001). In mildly decreased EF, there was no significant change (+0.3%, n.s.). Nisoldipine produced an increase in pump function (+2%) in the group with extremely decreased EF up to 9% in some individual cases. A significant increase (+5%) was achieved in moderately decreased EF, while patients with mildly decreased EF did not respond. Thus, nisoldipine may be indicated in the treatment of heart failure after repeated myocardial infarctions, in particular in patients with severely decreased ejection fraction."} {"id": "PMID:1282616", "title": "Effect of calcium antagonists on exercise tests.", "content": "The aim of this study was to investigate the anti-ischemic and antianginal activity and the duration of the new dihydropyridine calcium blocker nisoldipine (NIS) in patients with stable angina pectoris. The research was carried out on 16 patients, all male, 41-68 (mean of 58) years of age, with stable angina pectoris and fixed ischemic threshold (variations < 15%). After a 10-day washout period, patients were randomized to treatment with either 10 mg of nisoldipine or placebo (PL), twice daily for 21 days, according to a double-blind, crossover design. Patients underwent maximal symptom-limited exercise testing at 10 W/min on a bicycle ergometer, twice during the washout period, and once at the end of each treatment period, 3 and 12 h after oral administration of the drugs. In comparison with placebo, nisoldipine increased the ischemic threshold (N, 704 +/- 45 s; PL, 548 +/- 35 s; p < 0.01) and anginal threshold (N, 766 +/- 44 s; PL, 699 +/- 42 s; p < 0.01) for at least 12 h, and the ST-segment depression significantly decreased at maximal work (PL, 2.4 +/- 0.1 mm; N, 1.8 +/- 0.2 mm; p < 0.01) and at maximal common work (PL, 2.4 +/- 0.1 mm; N, 1.15 +/- 0.2 mm; p < 0.01). Similar to placebo the rate-pressure product was not significantly changed at higher submaximal effort after N, but it was significantly increased at the level of ischemic threshold, suggesting an increase in coronary blood flow to ischemic zones. Nisoldipine possesses anti-ischemic and antianginal activity lasting at least 12 h. This activity seems to be due to an increase in coronary blood flow to ischemic zones.", "contents": "Effect of calcium antagonists on exercise tests. The aim of this study was to investigate the anti-ischemic and antianginal activity and the duration of the new dihydropyridine calcium blocker nisoldipine (NIS) in patients with stable angina pectoris. The research was carried out on 16 patients, all male, 41-68 (mean of 58) years of age, with stable angina pectoris and fixed ischemic threshold (variations < 15%). After a 10-day washout period, patients were randomized to treatment with either 10 mg of nisoldipine or placebo (PL), twice daily for 21 days, according to a double-blind, crossover design. Patients underwent maximal symptom-limited exercise testing at 10 W/min on a bicycle ergometer, twice during the washout period, and once at the end of each treatment period, 3 and 12 h after oral administration of the drugs. In comparison with placebo, nisoldipine increased the ischemic threshold (N, 704 +/- 45 s; PL, 548 +/- 35 s; p < 0.01) and anginal threshold (N, 766 +/- 44 s; PL, 699 +/- 42 s; p < 0.01) for at least 12 h, and the ST-segment depression significantly decreased at maximal work (PL, 2.4 +/- 0.1 mm; N, 1.8 +/- 0.2 mm; p < 0.01) and at maximal common work (PL, 2.4 +/- 0.1 mm; N, 1.15 +/- 0.2 mm; p < 0.01). Similar to placebo the rate-pressure product was not significantly changed at higher submaximal effort after N, but it was significantly increased at the level of ischemic threshold, suggesting an increase in coronary blood flow to ischemic zones. Nisoldipine possesses anti-ischemic and antianginal activity lasting at least 12 h. This activity seems to be due to an increase in coronary blood flow to ischemic zones."} {"id": "PMID:1282617", "title": "Effects of nisoldipine in coronary artery disease: a radioisotopic approach.", "content": "The clinical, electrocardiographic, and scintigraphic effects of oral administration of nisoldipine were investigated using two separate study protocols. In the first, the acute effects of nisoldipine were evaluated by means of nuclear ventricolography and demonstrated no deleterious effects on global contractility and an amelioration of several hypokinetic segments. In the second protocol, myocardial perfusion effects were evaluated by means of tomoscintigraphy. An improvement of segmental uptake of thallium was caused by nisoldipine. The addition of atenolol markedly reduced the rate-pressure product and further improved myocardial perfusion.", "contents": "Effects of nisoldipine in coronary artery disease: a radioisotopic approach. The clinical, electrocardiographic, and scintigraphic effects of oral administration of nisoldipine were investigated using two separate study protocols. In the first, the acute effects of nisoldipine were evaluated by means of nuclear ventricolography and demonstrated no deleterious effects on global contractility and an amelioration of several hypokinetic segments. In the second protocol, myocardial perfusion effects were evaluated by means of tomoscintigraphy. An improvement of segmental uptake of thallium was caused by nisoldipine. The addition of atenolol markedly reduced the rate-pressure product and further improved myocardial perfusion."} {"id": "PMID:1282618", "title": "Reversible and irreversible left ventricular dysfunction after acute myocardial infarction.", "content": "Left ventricular function after acute myocardial infarction depends on several mechanisms leading to left ventricular remodeling: (a) infarct size and healing and (b) adaptive changes involving both the dysfunctioning but viable myocardium (hibernating and stunned myocardium) and the nonischemic myocardium. The prognosis after acute myocardial infarction is strongly related to regional and global left ventricular function and the loss of dysfunctioning viable myocardium is a main factor in the worsening in left ventricular function in survivors of the acute phase. Thus, medical strategies should exert their beneficial effect on the \"mechanical instability\" of ventricular myocardium by saving the viable myocardium. beta-Blocker therapy has been shown to be effective in improving the prognosis via anti-ischemic and antiarrhythmic actions. The combination of metoprolol and nisoldipine seems to be able to preserve the contractile function of viable myocardium in the first 6 months after acute myocardial infarction.", "contents": "Reversible and irreversible left ventricular dysfunction after acute myocardial infarction. Left ventricular function after acute myocardial infarction depends on several mechanisms leading to left ventricular remodeling: (a) infarct size and healing and (b) adaptive changes involving both the dysfunctioning but viable myocardium (hibernating and stunned myocardium) and the nonischemic myocardium. The prognosis after acute myocardial infarction is strongly related to regional and global left ventricular function and the loss of dysfunctioning viable myocardium is a main factor in the worsening in left ventricular function in survivors of the acute phase. Thus, medical strategies should exert their beneficial effect on the \"mechanical instability\" of ventricular myocardium by saving the viable myocardium. beta-Blocker therapy has been shown to be effective in improving the prognosis via anti-ischemic and antiarrhythmic actions. The combination of metoprolol and nisoldipine seems to be able to preserve the contractile function of viable myocardium in the first 6 months after acute myocardial infarction."} {"id": "PMID:1282619", "title": "Effects of prolonged nisoldipine administration on the \"hibernating\" myocardium.", "content": "To assess the effects of nisoldipine on chronically underperfused myocardial areas (\"hibernating myocardium\"), the global and regional left ventricular (LV) function was analyzed before and after 2 months of double-blind monotherapy with nisoldipine (10 mg twice daily) or placebo in 17 patients with a previous anterior myocardial infarction. The baseline LV ejection fraction ranged from 34 to 51%, and no patient had heart failure. Compared to placebo, nisoldipine significantly lowered the LV systolic pressure and end-diastolic pressure (-3 vs. +6 mmHg with placebo; p < 0.01) and the LV pressure at the time of mitral valve opening (-2.0 +/- 3.4 vs. +3.5 +/- 3.0 mm Hg; p < 0.01). Despite this reduction in driving pressure, the global LV early peak filling rate improved only with nisoldipine and this improvement was related to a selective increase in the expansion rate of the anterior areas, from 1,010 +/- 360 to 1,339 +/- 496 mm2/s (p < 0.001). The time to regional peak filling rate (-8%; p < 0.01), the asynchrony of diastolic wall motion, and the regional ejection fraction (33 +/- 10 to 38 +/- 12%; p < 0.001) also improved in the anterior areas with nisoldipine but not with placebo. In contrast, in the inferior control zones, the regional ejection fraction and filling rate remained unchanged, both when compared to baseline and to placebo. In conclusion, prolonged nisoldipine therapy had no significant effect on the normal myocardium but improved systolic and diastolic function in hypokinetic areas.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of prolonged nisoldipine administration on the \"hibernating\" myocardium. To assess the effects of nisoldipine on chronically underperfused myocardial areas (\"hibernating myocardium\"), the global and regional left ventricular (LV) function was analyzed before and after 2 months of double-blind monotherapy with nisoldipine (10 mg twice daily) or placebo in 17 patients with a previous anterior myocardial infarction. The baseline LV ejection fraction ranged from 34 to 51%, and no patient had heart failure. Compared to placebo, nisoldipine significantly lowered the LV systolic pressure and end-diastolic pressure (-3 vs. +6 mmHg with placebo; p < 0.01) and the LV pressure at the time of mitral valve opening (-2.0 +/- 3.4 vs. +3.5 +/- 3.0 mm Hg; p < 0.01). Despite this reduction in driving pressure, the global LV early peak filling rate improved only with nisoldipine and this improvement was related to a selective increase in the expansion rate of the anterior areas, from 1,010 +/- 360 to 1,339 +/- 496 mm2/s (p < 0.001). The time to regional peak filling rate (-8%; p < 0.01), the asynchrony of diastolic wall motion, and the regional ejection fraction (33 +/- 10 to 38 +/- 12%; p < 0.001) also improved in the anterior areas with nisoldipine but not with placebo. In contrast, in the inferior control zones, the regional ejection fraction and filling rate remained unchanged, both when compared to baseline and to placebo. In conclusion, prolonged nisoldipine therapy had no significant effect on the normal myocardium but improved systolic and diastolic function in hypokinetic areas.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282621", "title": "Kininogenase of the aortic wall in spontaneously hypertensive rats.", "content": "We determined kinin-generating activity (kininogenase) in the thoracic aorta of spontaneously hypertensive rats (SHRs) at age 5 and 15 weeks and in appropriately age-matched Wistar-Kyoto (WKY) rats. Aorta homogenates were incubated with partially purified dog kininogen, and the resulting kinins were extracted with ethanol. The kinins were determined by a sensitive kinin radioimmunoassay (RIA). Kininogenase activity was expressed as mean +/- SEM, picogram kinin generated/mg x protein/h. Active kininogenase in SHR was approximately one-third in 5-week-old and about one-fifth in 15-week-old rats when compared with their normotensive controls. Total kininogenase activity in SHRs was approximately 80% and 58% of the normotensive controls at ages 5 weeks and 15 weeks, respectively. Active enzyme was 14% of the total in 5-week-old SHRs, and it was only 5% of the total in 15-week-old SHRs. It seems unlikely that the changes in kininogenase are secondary to hypertension because blood pressor is only marginally elevated at 5 weeks according to the literature. We hypothesize that genetic hypertensive rats may suffer from an inherent deficiency in the kininogenase activity of the vascular wall. The deficiency may also be in the mechanism of activation of precursor enzyme.", "contents": "Kininogenase of the aortic wall in spontaneously hypertensive rats. We determined kinin-generating activity (kininogenase) in the thoracic aorta of spontaneously hypertensive rats (SHRs) at age 5 and 15 weeks and in appropriately age-matched Wistar-Kyoto (WKY) rats. Aorta homogenates were incubated with partially purified dog kininogen, and the resulting kinins were extracted with ethanol. The kinins were determined by a sensitive kinin radioimmunoassay (RIA). Kininogenase activity was expressed as mean +/- SEM, picogram kinin generated/mg x protein/h. Active kininogenase in SHR was approximately one-third in 5-week-old and about one-fifth in 15-week-old rats when compared with their normotensive controls. Total kininogenase activity in SHRs was approximately 80% and 58% of the normotensive controls at ages 5 weeks and 15 weeks, respectively. Active enzyme was 14% of the total in 5-week-old SHRs, and it was only 5% of the total in 15-week-old SHRs. It seems unlikely that the changes in kininogenase are secondary to hypertension because blood pressor is only marginally elevated at 5 weeks according to the literature. We hypothesize that genetic hypertensive rats may suffer from an inherent deficiency in the kininogenase activity of the vascular wall. The deficiency may also be in the mechanism of activation of precursor enzyme."} {"id": "PMID:1282623", "title": "The angiotensin I-converting enzyme (kininase II): molecular organization and regulation of its expression in humans.", "content": "Protein sequencing and molecular cloning of human endothelial angiotensin I-converting enzyme (ACE; kininase II), have led to a description of the structure of the enzyme and to several questions concerning the intracellular maturation of ACE and the mechanisms of enzyme action. With the help of recombinant ACE expression in mammalian cells and site-directed mutagenesis, a model for the maturation of ACE in endothelial cells has been proposed. This model comprises transmembrane anchoring of the membrane-bound ACE near its carboxyterminal extremity, and post-translational cleavage of the anchor in the secreted form. The endothelial ACE displays a high degree of internal homology between two large peptidic domains that each bears a consensus sequence for zinc binding and therefore a putative active site. The testicular ACE, however, encoded from the same gene by a shorter mRNA, contains only the carboxyterminal half of endothelial ACE and therefore a single active site. Expression of ACE mutants with only one intact homologous domain, however, indicates that in endothelial ACE both domains are enzymatically active. Further characterization of these two active sites of endothelial ACE is in progress. In humans, population studies have indicated that the large interindividual variability in plasma ACE levels is partly genetically determined and under the influence of a major gene effect. This was later confirmed and extended by the observation of an insertion-deletion polymorphism of the ACE gene that is associated with the level of ACE in plasma. The clinical implications of these observations are discussed.", "contents": "The angiotensin I-converting enzyme (kininase II): molecular organization and regulation of its expression in humans. Protein sequencing and molecular cloning of human endothelial angiotensin I-converting enzyme (ACE; kininase II), have led to a description of the structure of the enzyme and to several questions concerning the intracellular maturation of ACE and the mechanisms of enzyme action. With the help of recombinant ACE expression in mammalian cells and site-directed mutagenesis, a model for the maturation of ACE in endothelial cells has been proposed. This model comprises transmembrane anchoring of the membrane-bound ACE near its carboxyterminal extremity, and post-translational cleavage of the anchor in the secreted form. The endothelial ACE displays a high degree of internal homology between two large peptidic domains that each bears a consensus sequence for zinc binding and therefore a putative active site. The testicular ACE, however, encoded from the same gene by a shorter mRNA, contains only the carboxyterminal half of endothelial ACE and therefore a single active site. Expression of ACE mutants with only one intact homologous domain, however, indicates that in endothelial ACE both domains are enzymatically active. Further characterization of these two active sites of endothelial ACE is in progress. In humans, population studies have indicated that the large interindividual variability in plasma ACE levels is partly genetically determined and under the influence of a major gene effect. This was later confirmed and extended by the observation of an insertion-deletion polymorphism of the ACE gene that is associated with the level of ACE in plasma. The clinical implications of these observations are discussed."} {"id": "PMID:1282624", "title": "Bradykinin degrading activity in cultured human endothelial cells.", "content": "The role of angiotensin-converting enzyme (ACE), neutral endopeptidase 24.11 (NEP), and other peptidases in the endothelial degradation of bradykinin was investigated in cultured human umbilical vein endothelial cells (HUVEC). The major part of the kininase II activity on intact cells was attributed to ACE activity, the minor part to NEP activity. Amastatin, as aminopeptidase inhibitor, and DL-2-mercaptomethyl-3-guanidinoethyl-thiopropionic acid (MGTA), an inhibitor of kininase I, did not affect endothelial kininase activity. The decline of the bradykinin concentrations in the supernatant of intact endothelial monolayer indicated a total kininase activity of 289 +/- 27 fmol/min/dish. The calculated activity of ACE was 223 fmol/min/dish and the neutral endopeptidase activity was 51 fmol/min/dish. Thus, ACE and neutral endopeptidase are the main kininases in the degradation of bradykinin by intact endothelial cells. In contrast to the intact endothelial monolayers, in homogenates additional kininase activity was found which was not affected by either ACE and NEP inhibitors nor by amastatin and MGTA.", "contents": "Bradykinin degrading activity in cultured human endothelial cells. The role of angiotensin-converting enzyme (ACE), neutral endopeptidase 24.11 (NEP), and other peptidases in the endothelial degradation of bradykinin was investigated in cultured human umbilical vein endothelial cells (HUVEC). The major part of the kininase II activity on intact cells was attributed to ACE activity, the minor part to NEP activity. Amastatin, as aminopeptidase inhibitor, and DL-2-mercaptomethyl-3-guanidinoethyl-thiopropionic acid (MGTA), an inhibitor of kininase I, did not affect endothelial kininase activity. The decline of the bradykinin concentrations in the supernatant of intact endothelial monolayer indicated a total kininase activity of 289 +/- 27 fmol/min/dish. The calculated activity of ACE was 223 fmol/min/dish and the neutral endopeptidase activity was 51 fmol/min/dish. Thus, ACE and neutral endopeptidase are the main kininases in the degradation of bradykinin by intact endothelial cells. In contrast to the intact endothelial monolayers, in homogenates additional kininase activity was found which was not affected by either ACE and NEP inhibitors nor by amastatin and MGTA."} {"id": "PMID:1282625", "title": "Effect of bradykinin on arteries and veins in systemic and pulmonary circulation.", "content": "Bradykinin is a potent vasodilating and natriuretic peptide, which is potentiated by angiotensin-converting enzyme (ACE) inhibitors. In our investigations we studied the effect of bradykinin on systemic and pulmonary circulation as well as on dorsal hand vein tone. The effects of bradykinin on systemic and pulmonary circulation were tested by injection of bradykinin into the right atrium. Parameters were determined for blood pressure, cardiac output, ECG and mean pressure in pulmonary artery. Heart rate, total peripheral resistance, pulmonary vascular resistance, and pulmonary arteriolar resistance were calculated by these measured parameters. The data raised in our investigations showed clearly that bradykinin reduced blood pressure by reducing total peripheral vascular resistance in a dose-dependent manner. In pulmonary circulation bradykinin develops a direct effect. All circulatory actions of bradykinin are not mediated by prostaglandins, since inhibition of prostaglandin synthesis by indomethacin (100-150 mg) was without any effect. ACE inhibition by ramipril (5 mg) or captopril (50 mg) potentiated all effects of bradykinin about 20- to 50-fold, whereas it decreased angiotensin I effects only about four- to fivefold. These results suggest, that endogenous kinins, if they will be similarly potentiated by ACE inhibition like the exogenous bradykinin in our experiments, might play an important role in the blood pressure lowering effect of ACE inhibitors. Dorsal hand vein tone was reduced by bradykinin too, indicating that kinins can lower cardiac preload by increasing venous blood pooling.", "contents": "Effect of bradykinin on arteries and veins in systemic and pulmonary circulation. Bradykinin is a potent vasodilating and natriuretic peptide, which is potentiated by angiotensin-converting enzyme (ACE) inhibitors. In our investigations we studied the effect of bradykinin on systemic and pulmonary circulation as well as on dorsal hand vein tone. The effects of bradykinin on systemic and pulmonary circulation were tested by injection of bradykinin into the right atrium. Parameters were determined for blood pressure, cardiac output, ECG and mean pressure in pulmonary artery. Heart rate, total peripheral resistance, pulmonary vascular resistance, and pulmonary arteriolar resistance were calculated by these measured parameters. The data raised in our investigations showed clearly that bradykinin reduced blood pressure by reducing total peripheral vascular resistance in a dose-dependent manner. In pulmonary circulation bradykinin develops a direct effect. All circulatory actions of bradykinin are not mediated by prostaglandins, since inhibition of prostaglandin synthesis by indomethacin (100-150 mg) was without any effect. ACE inhibition by ramipril (5 mg) or captopril (50 mg) potentiated all effects of bradykinin about 20- to 50-fold, whereas it decreased angiotensin I effects only about four- to fivefold. These results suggest, that endogenous kinins, if they will be similarly potentiated by ACE inhibition like the exogenous bradykinin in our experiments, might play an important role in the blood pressure lowering effect of ACE inhibitors. Dorsal hand vein tone was reduced by bradykinin too, indicating that kinins can lower cardiac preload by increasing venous blood pooling."} {"id": "PMID:1282626", "title": "Antagonizing and measurement: approaches to understanding of hemodynamic effects of kinins.", "content": "Hemodynamic effects of the kallikrein-kinin system can be investigated by experimental administration of specific kinin antagonists and by measurement of kinin levels in the circulating blood. In conscious normal rats, the bradykinin analog B4162 blunts the hypotensive effect of exogenous bradykinin. This kinin antagonist has no blood pressure effect in control rats, but it enhances the pressor effect of vasoconstrictor substances such as vasopressin or angiotensin II when they are infused at subpressor doses. Endogenous kinins may therefore participate in blood pressure regulation by antagonizing pressor substances. Plasma levels of endogenous kinins are normally in the low picomolar range. They are rapidly generated and destroyed in biological fluids. Thus, measurement of plasma kinins requires sensitive assays based on high-affinity antibodies and careful sample-handling techniques. Nonpolar solid-phase extraction on phenylsilylsilica provides a rapid, reliable, and easy extraction of kinins from plasma with constant and high recoveries.", "contents": "Antagonizing and measurement: approaches to understanding of hemodynamic effects of kinins. Hemodynamic effects of the kallikrein-kinin system can be investigated by experimental administration of specific kinin antagonists and by measurement of kinin levels in the circulating blood. In conscious normal rats, the bradykinin analog B4162 blunts the hypotensive effect of exogenous bradykinin. This kinin antagonist has no blood pressure effect in control rats, but it enhances the pressor effect of vasoconstrictor substances such as vasopressin or angiotensin II when they are infused at subpressor doses. Endogenous kinins may therefore participate in blood pressure regulation by antagonizing pressor substances. Plasma levels of endogenous kinins are normally in the low picomolar range. They are rapidly generated and destroyed in biological fluids. Thus, measurement of plasma kinins requires sensitive assays based on high-affinity antibodies and careful sample-handling techniques. Nonpolar solid-phase extraction on phenylsilylsilica provides a rapid, reliable, and easy extraction of kinins from plasma with constant and high recoveries."} {"id": "PMID:1282627", "title": "Changes in peripheral sympathetic outflow of pithed spontaneously hypertensive rats after bradykinin and DesArg-bradykinin infusions: influence of converting-enzyme inhibition.", "content": "Because converting enzyme and kininase II are identical enzymes and probably influence both the biosynthesis of angiotensin II and the metabolism of bradykinin, we investigated the effects of bradykinin and desArg-bradykinin on the sympathetic outflow of pithed spontaneously hypertensive rats (SHRs) before and after acute or chronic inhibition of the converting enzyme by ramipril. Sympathetic outflow was induced by preganglionic electrical stimulation of the spinal cord and measured as circulating, stimulation dependent norepinephrine and epinephrine by high-performance liquid chromatography (HPLC) and electrochemical detection. Bradykinin increased dose-dependently norepinephrine and epinephrine release, particularly when converting enzyme was inhibited. DesArg-bradykinin did not influence norepinephrine outflow but caused a dose-dependent increase in epinephrine release only after converting-enzyme inhibition. It is suggested that both bradykinin and desArg-bradykinin could compensate for the lack of effect of angiotensin II on sympathetic outflow.", "contents": "Changes in peripheral sympathetic outflow of pithed spontaneously hypertensive rats after bradykinin and DesArg-bradykinin infusions: influence of converting-enzyme inhibition. Because converting enzyme and kininase II are identical enzymes and probably influence both the biosynthesis of angiotensin II and the metabolism of bradykinin, we investigated the effects of bradykinin and desArg-bradykinin on the sympathetic outflow of pithed spontaneously hypertensive rats (SHRs) before and after acute or chronic inhibition of the converting enzyme by ramipril. Sympathetic outflow was induced by preganglionic electrical stimulation of the spinal cord and measured as circulating, stimulation dependent norepinephrine and epinephrine by high-performance liquid chromatography (HPLC) and electrochemical detection. Bradykinin increased dose-dependently norepinephrine and epinephrine release, particularly when converting enzyme was inhibited. DesArg-bradykinin did not influence norepinephrine outflow but caused a dose-dependent increase in epinephrine release only after converting-enzyme inhibition. It is suggested that both bradykinin and desArg-bradykinin could compensate for the lack of effect of angiotensin II on sympathetic outflow."} {"id": "PMID:1282628", "title": "Influence of angiotensin-converting enzyme inhibition on sympathetic neurotransmission: possible roles of bradykinin and prostaglandins.", "content": "Effects of angiotensin-converting enzyme (ACE) inhibitors on sympathetic neurotransmission have generally been ascribed to their ability to block angiotensin II (Ang II) formation, but they also inhibit the degradation of vasoactive kinins, such as bradykinin. The latter may, in turn, lead to enhanced prostaglandin formation. Prostaglandins have been reported to influence sympathetic neurotransmission at different sites; much less is known about the influence of bradykinin due to the lack (until recently) of specific and effective bradykinin receptor antagonists, and difficulties with measurements of true plasma or tissue levels of bradykinin. Bradykinin may modulate sympathetic activity via a central stimulatory action and via activation of sensory input to the central nervous system; however, the importance of bradykinin for central effects of ACE inhibition remain to be established. At the sympathetic neuro-effector junction, results are more conflicting. Thus, bradykinin has been reported to enhance or reduce peripheral noradrenergic transmission or even lack any effect. Possible explanations for the differing results obtained include species and/or tissue differences in the responses to bradykinin. Also, the effects of bradykinin may be influenced by enhanced formation of prostaglandins and/or endothelium-derived relaxing factor (EDRF), which may contribute to the confusion. As most studies have been performed under in vitro conditions and with high doses of bradykinin, the physiological relevance of the data may be questioned.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Influence of angiotensin-converting enzyme inhibition on sympathetic neurotransmission: possible roles of bradykinin and prostaglandins. Effects of angiotensin-converting enzyme (ACE) inhibitors on sympathetic neurotransmission have generally been ascribed to their ability to block angiotensin II (Ang II) formation, but they also inhibit the degradation of vasoactive kinins, such as bradykinin. The latter may, in turn, lead to enhanced prostaglandin formation. Prostaglandins have been reported to influence sympathetic neurotransmission at different sites; much less is known about the influence of bradykinin due to the lack (until recently) of specific and effective bradykinin receptor antagonists, and difficulties with measurements of true plasma or tissue levels of bradykinin. Bradykinin may modulate sympathetic activity via a central stimulatory action and via activation of sensory input to the central nervous system; however, the importance of bradykinin for central effects of ACE inhibition remain to be established. At the sympathetic neuro-effector junction, results are more conflicting. Thus, bradykinin has been reported to enhance or reduce peripheral noradrenergic transmission or even lack any effect. Possible explanations for the differing results obtained include species and/or tissue differences in the responses to bradykinin. Also, the effects of bradykinin may be influenced by enhanced formation of prostaglandins and/or endothelium-derived relaxing factor (EDRF), which may contribute to the confusion. As most studies have been performed under in vitro conditions and with high doses of bradykinin, the physiological relevance of the data may be questioned.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282629", "title": "Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology.", "content": "Bradykinin is susceptible to degradation by a variety of endo- and exopeptidases. These include aminopeptidase P, meprin, endopeptidase 24.15, prolyl endopeptidase, neutral endopeptidase 24.11, angiotensin I-converting enzyme, carboxypeptidase N, carboxypeptidase M, and deamidase. These peptidases are widely distributed in various tissues and cells in the body, and their subcellular locations vary as well. Because bradykinin is inactivated (for binding the B2 receptor) when any of its peptide bonds are cleaved, all of these enzymes qualify as potential \"kininases\" in vivo; however, the importance of a particular enzyme as a kininase will depend on its localization, access to bradykinin, and the presence of other peptidases. In addition, these peptidases can cleave a variety of other peptide hormone substrates. Determination of the importance of a peptidase in the inactivation of bradykinin during a particular physiological response can be difficult, but specific peptidase inhibitors and kinin receptor antagonists are useful tools in investigating these questions.", "contents": "Bradykinin-degrading enzymes: structure, function, distribution, and potential roles in cardiovascular pharmacology. Bradykinin is susceptible to degradation by a variety of endo- and exopeptidases. These include aminopeptidase P, meprin, endopeptidase 24.15, prolyl endopeptidase, neutral endopeptidase 24.11, angiotensin I-converting enzyme, carboxypeptidase N, carboxypeptidase M, and deamidase. These peptidases are widely distributed in various tissues and cells in the body, and their subcellular locations vary as well. Because bradykinin is inactivated (for binding the B2 receptor) when any of its peptide bonds are cleaved, all of these enzymes qualify as potential \"kininases\" in vivo; however, the importance of a particular enzyme as a kininase will depend on its localization, access to bradykinin, and the presence of other peptidases. In addition, these peptidases can cleave a variety of other peptide hormone substrates. Determination of the importance of a peptidase in the inactivation of bradykinin during a particular physiological response can be difficult, but specific peptidase inhibitors and kinin receptor antagonists are useful tools in investigating these questions."} {"id": "PMID:1282630", "title": "Anti-idiotypic antibodies against the kinin receptor.", "content": "Three sets of monoclonal antibodies against bradykinin (MBK1, MBK2, and MBK3) were generated by somatic cell fusion, characterized by their peptide specificity, and compared with the known ligand specificity of the kinin receptor subtypes. By these criteria, the paratope of MBK3 resembled the B2 receptor binding site, whereas MBK1 shared principal binding characteristics with the B1 receptor. Anti-idiotypic antibodies against MBK1, MBK2, and MBK3 were raised in rabbit and sheep. Specificity of the network components was verified by inhibition experiments on the level of peptide, idiotype, and anti-idiotype. Anti-idiotypic antibodies against MBK3 recognized a conformation-dependent epitope which was binding site-related. Binding studies on human foreskin fibroblasts and guinea pig ileum showed mutual displacement of the anti-idiotypic antibody and bradykinin at the binding site pointing to a specific interaction of the antibody with the receptor from various species. An agonist activity of the antibodies, demonstrated in human (inositolphosphate pathway) and mouse (prostaglandin pathway) fibroblasts indicated that the anti-idiotypes bear an internal image of the ligand epitope. This molecular mimicry, which was further substantiated by the detection of bradykinin-specific anti-anti-idiotypic antibodies, provides the structural basis for the observed cross-reactivity over species borders.", "contents": "Anti-idiotypic antibodies against the kinin receptor. Three sets of monoclonal antibodies against bradykinin (MBK1, MBK2, and MBK3) were generated by somatic cell fusion, characterized by their peptide specificity, and compared with the known ligand specificity of the kinin receptor subtypes. By these criteria, the paratope of MBK3 resembled the B2 receptor binding site, whereas MBK1 shared principal binding characteristics with the B1 receptor. Anti-idiotypic antibodies against MBK1, MBK2, and MBK3 were raised in rabbit and sheep. Specificity of the network components was verified by inhibition experiments on the level of peptide, idiotype, and anti-idiotype. Anti-idiotypic antibodies against MBK3 recognized a conformation-dependent epitope which was binding site-related. Binding studies on human foreskin fibroblasts and guinea pig ileum showed mutual displacement of the anti-idiotypic antibody and bradykinin at the binding site pointing to a specific interaction of the antibody with the receptor from various species. An agonist activity of the antibodies, demonstrated in human (inositolphosphate pathway) and mouse (prostaglandin pathway) fibroblasts indicated that the anti-idiotypes bear an internal image of the ligand epitope. This molecular mimicry, which was further substantiated by the detection of bradykinin-specific anti-anti-idiotypic antibodies, provides the structural basis for the observed cross-reactivity over species borders."} {"id": "PMID:1282631", "title": "Role of endothelium-derived bradykinin in the control of vascular tone.", "content": "We have investigated the effects of angiotensin-converting enzyme (ACE) inhibitors on intracellular Ca2+ levels in human cultured endothelial cells and on endothelial autacoid formation in endothelium-intact bovine coronary arteries and in isolated perfused rabbit and rat hearts. Incubation of cultured endothelial cells with ramiprilat (0.3 microM) caused a maintained increase in resting intracellular Ca2+. This effect was long-lasting, accompanied by an increased formation of both nitric oxide (NO) and prostacyclin (PGI2), and was abolished by the specific B2-kinin receptor antagonist Hoe 140. Ramiprilat also significantly enhanced the increase in intracellular Ca2+ elicited by bradykinin (3 nM). In endothelium-intact bovine coronary arteries, moexiprilat (0.3 microM), like bradykinin (30 nM), caused a nearly twofold increase in the vascular cGMP content which was abolished by both NG-nitro-L-arginine (30 microM) and removal of the endothelium. The functional consequences of this ACE inhibitor-induced increase in vascular cGMP content were reflected by a distinct relaxation of the coronary segments preconstricted with prostaglandin F2 alpha. In the isolated perfused rabbit heart, ramiprilat (0.3 microM) affected neither resting vascular tone nor endothelial autacoid release; however, the vasodilation and release of PGI2 in response to exogenously applied bradykinin (10 nM) were significantly enhanced by ramiprilat. This effect was also seen using moexiprilat (0.1 microM) in the isolated perfused rat heart. Although these findings suggest that endothelium-derived bradykinin is not involved in the control of resting vascular tone in the coronary microcirculation of the rabbit and the rat, there appears to be significant ACE activity to modulate bradykinin-induced endothelial autacoid formation.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Role of endothelium-derived bradykinin in the control of vascular tone. We have investigated the effects of angiotensin-converting enzyme (ACE) inhibitors on intracellular Ca2+ levels in human cultured endothelial cells and on endothelial autacoid formation in endothelium-intact bovine coronary arteries and in isolated perfused rabbit and rat hearts. Incubation of cultured endothelial cells with ramiprilat (0.3 microM) caused a maintained increase in resting intracellular Ca2+. This effect was long-lasting, accompanied by an increased formation of both nitric oxide (NO) and prostacyclin (PGI2), and was abolished by the specific B2-kinin receptor antagonist Hoe 140. Ramiprilat also significantly enhanced the increase in intracellular Ca2+ elicited by bradykinin (3 nM). In endothelium-intact bovine coronary arteries, moexiprilat (0.3 microM), like bradykinin (30 nM), caused a nearly twofold increase in the vascular cGMP content which was abolished by both NG-nitro-L-arginine (30 microM) and removal of the endothelium. The functional consequences of this ACE inhibitor-induced increase in vascular cGMP content were reflected by a distinct relaxation of the coronary segments preconstricted with prostaglandin F2 alpha. In the isolated perfused rabbit heart, ramiprilat (0.3 microM) affected neither resting vascular tone nor endothelial autacoid release; however, the vasodilation and release of PGI2 in response to exogenously applied bradykinin (10 nM) were significantly enhanced by ramiprilat. This effect was also seen using moexiprilat (0.1 microM) in the isolated perfused rat heart. Although these findings suggest that endothelium-derived bradykinin is not involved in the control of resting vascular tone in the coronary microcirculation of the rabbit and the rat, there appears to be significant ACE activity to modulate bradykinin-induced endothelial autacoid formation.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282632", "title": "Local potentiation of bradykinin-induced vasodilation by converting-enzyme inhibition in isolated coronary arteries.", "content": "The interaction of angiotensin-converting enzyme (ACE) inhibitors and bradykinin was investigated in isolated bovine and human coronary arteries. Rings with and without endothelium were mounted in organ chambers for measurement of isometric force. The effects of the ACE inhibitors lisinopril, enalaprilat, fosinoprilat, ramiprilat, and captopril were determined during submaximal stimulation with bradykinin or other vasodilators. Lisinopril and captopril alone did not affect vascular tone; however, in rings with endothelium partially relaxed with bradykinin (> or = 10(-10) M), all ACE inhibitors caused further relaxations. Lisinopril did not affect bradykinin concentrations in the incubation medium. Mechanical removal of the endothelium or incubation with nitro-L-arginine or the bradykinin2-receptor antagonist Hoe 140 prevented the relaxations to bradykinin and lisinopril. Other vasodilators including acetylcholine, adenosine diphosphate, substance P, or SIN-1 did not prime the rings to respond to ACE inhibitors. Endothelium-dependent relaxations to lisinopril were also observed in human coronary arteries treated with bradykinin (> or = 10(-7) M). Thus, ACE inhibitors potentiate endothelium-dependent relaxations to submaximal concentrations of bradykinin in bovine and human coronary arteries. This local mechanism occurs regardless of elevated bradykinin concentrations in the blood and reduced angiotensin II generation.", "contents": "Local potentiation of bradykinin-induced vasodilation by converting-enzyme inhibition in isolated coronary arteries. The interaction of angiotensin-converting enzyme (ACE) inhibitors and bradykinin was investigated in isolated bovine and human coronary arteries. Rings with and without endothelium were mounted in organ chambers for measurement of isometric force. The effects of the ACE inhibitors lisinopril, enalaprilat, fosinoprilat, ramiprilat, and captopril were determined during submaximal stimulation with bradykinin or other vasodilators. Lisinopril and captopril alone did not affect vascular tone; however, in rings with endothelium partially relaxed with bradykinin (> or = 10(-10) M), all ACE inhibitors caused further relaxations. Lisinopril did not affect bradykinin concentrations in the incubation medium. Mechanical removal of the endothelium or incubation with nitro-L-arginine or the bradykinin2-receptor antagonist Hoe 140 prevented the relaxations to bradykinin and lisinopril. Other vasodilators including acetylcholine, adenosine diphosphate, substance P, or SIN-1 did not prime the rings to respond to ACE inhibitors. Endothelium-dependent relaxations to lisinopril were also observed in human coronary arteries treated with bradykinin (> or = 10(-7) M). Thus, ACE inhibitors potentiate endothelium-dependent relaxations to submaximal concentrations of bradykinin in bovine and human coronary arteries. This local mechanism occurs regardless of elevated bradykinin concentrations in the blood and reduced angiotensin II generation."} {"id": "PMID:1282633", "title": "Role of prostaglandins in the cardiovascular effects of bradykinin and angiotensin-converting enzyme inhibitors.", "content": "The cardiovascular effects of bradykinin require additional vasoactive mediators for a fully balanced response. This includes arachidonic acid (eicosatetraenoic acid) and its metabolites, the eicosanoids (prostaglandins, leukotrienes, thromboxanes, and others). Eicosanoid generation by bradykinin is started by binding of the peptide to specific B2 receptors at the plasma membrane. This initiates G-protein coupled stimulation of phospholipase C, IP3-induced increases in cytosolic Ca2+, and stimulation of protein kinase C. Arachidonic acid is liberated from membrane phospholipids primarily via Ca(2+)-induced stimulation of phospholipase A2 and converted into tissue-specific eicosanoids by enzymes in the vicinity. In vascular tissue, most of the available arachidonic acid is converted into vasodilator prostaglandins, i.e., prostacyclin (PGI2) and prostaglandin E2 (PGE2). These prostaglandins are involved in vasodilator actions of the kinins. There is also some evidence for generation of vasoconstrictor eicosanoids, such as thromboxane A2, under certain conditions. The biological significance of kinin-related prostaglandin formation becomes apparent after inhibition of kinin breakdown by ACE inhibitors. These compounds prevent generation of vasoconstrictor angiotensin II and stimulate endothelial eicosanoid formation via local kinin accumulation. There is evidence suggesting that kinin-induced prostaglandin generation contributes to anti-ischemic, inotropic, and blood pressure-lowering effects of the compounds. This also includes inhibition of polymorphonuclear leukocyte (PMN) accumulation in injured myocardial tissue, which is antagonized by PGI2-related pathways, stimulated by ACE inhibition and/or bradykinin.", "contents": "Role of prostaglandins in the cardiovascular effects of bradykinin and angiotensin-converting enzyme inhibitors. The cardiovascular effects of bradykinin require additional vasoactive mediators for a fully balanced response. This includes arachidonic acid (eicosatetraenoic acid) and its metabolites, the eicosanoids (prostaglandins, leukotrienes, thromboxanes, and others). Eicosanoid generation by bradykinin is started by binding of the peptide to specific B2 receptors at the plasma membrane. This initiates G-protein coupled stimulation of phospholipase C, IP3-induced increases in cytosolic Ca2+, and stimulation of protein kinase C. Arachidonic acid is liberated from membrane phospholipids primarily via Ca(2+)-induced stimulation of phospholipase A2 and converted into tissue-specific eicosanoids by enzymes in the vicinity. In vascular tissue, most of the available arachidonic acid is converted into vasodilator prostaglandins, i.e., prostacyclin (PGI2) and prostaglandin E2 (PGE2). These prostaglandins are involved in vasodilator actions of the kinins. There is also some evidence for generation of vasoconstrictor eicosanoids, such as thromboxane A2, under certain conditions. The biological significance of kinin-related prostaglandin formation becomes apparent after inhibition of kinin breakdown by ACE inhibitors. These compounds prevent generation of vasoconstrictor angiotensin II and stimulate endothelial eicosanoid formation via local kinin accumulation. There is evidence suggesting that kinin-induced prostaglandin generation contributes to anti-ischemic, inotropic, and blood pressure-lowering effects of the compounds. This also includes inhibition of polymorphonuclear leukocyte (PMN) accumulation in injured myocardial tissue, which is antagonized by PGI2-related pathways, stimulated by ACE inhibition and/or bradykinin."} {"id": "PMID:1282634", "title": "Heterogeneity of endothelium-dependent vasodilator effects of angiotensin-converting enzyme inhibitors: role of bradykinin generation during ACE inhibition.", "content": "Endothelium-derived mediators are released in response to shear stress and a variety of endogenous substances including bradykinin and angiotensins. They may contribute to the regulation of the renin-angiotensin system in the vascular wall and in the kidney. Bradykinin is a powerful agonist at endothelial cells, and the actions of this peptide, which is generated by components of the vascular wall, during angiotensin-converting enzyme (ACE) inhibition may determine some of the vascular effects of ACE inhibitors. In vitro studies demonstrate that the relaxations to bradykinin are mostly endothelium dependent and are mediated by nitric oxide, endothelium-derived hyperpolarizing factor, and/or vasodilator prostaglandins; however, these endothelium-derived relaxing factors do not always contribute simultaneously to the relaxations in every artery. The contribution of ACE in the termination of bradykinin action, relative to the other inactivation processes (including carboxypeptidases and internalization) also may determine the ability of ACE inhibitors to augment the effects of the kinin. Furthermore, it appears that the level of ACE activity and the potency of bradykinin, respectively, are not uniform in all preparations. In arteries in which bradykinin is very efficacious and in which ACE activity may be relatively low, ACE inhibitors may prolong but not amplify the responses to the peptide. The pharmacologic characteristics of the responses of the different vascular beds to bradykinin, together with the modulation of endothelium-dependent responses to other agonists (including purines), may be of importance in the heterogeneity of the vasodilator actions of ACE inhibitors.", "contents": "Heterogeneity of endothelium-dependent vasodilator effects of angiotensin-converting enzyme inhibitors: role of bradykinin generation during ACE inhibition. Endothelium-derived mediators are released in response to shear stress and a variety of endogenous substances including bradykinin and angiotensins. They may contribute to the regulation of the renin-angiotensin system in the vascular wall and in the kidney. Bradykinin is a powerful agonist at endothelial cells, and the actions of this peptide, which is generated by components of the vascular wall, during angiotensin-converting enzyme (ACE) inhibition may determine some of the vascular effects of ACE inhibitors. In vitro studies demonstrate that the relaxations to bradykinin are mostly endothelium dependent and are mediated by nitric oxide, endothelium-derived hyperpolarizing factor, and/or vasodilator prostaglandins; however, these endothelium-derived relaxing factors do not always contribute simultaneously to the relaxations in every artery. The contribution of ACE in the termination of bradykinin action, relative to the other inactivation processes (including carboxypeptidases and internalization) also may determine the ability of ACE inhibitors to augment the effects of the kinin. Furthermore, it appears that the level of ACE activity and the potency of bradykinin, respectively, are not uniform in all preparations. In arteries in which bradykinin is very efficacious and in which ACE activity may be relatively low, ACE inhibitors may prolong but not amplify the responses to the peptide. The pharmacologic characteristics of the responses of the different vascular beds to bradykinin, together with the modulation of endothelium-dependent responses to other agonists (including purines), may be of importance in the heterogeneity of the vasodilator actions of ACE inhibitors."} {"id": "PMID:1282635", "title": "Role of bradykinin in the cardiac effects of angiotensin-converting enzyme inhibitors.", "content": "Angiotensin-converting enzyme (ACE) inhibitors exert their beneficial effects not only via endocrine mechanisms, but most probably also via interference with autocrine-paracrine actions involving local renin-angiotensin and kallikrein-kinin systems with subsequent autacoid release. Inhibition of ACE (kininase II) results in the reduction of angiotensin II generation and kinin degradation, leading to beneficial cardiovascular effects. Bradykinin and prostacyclin release from isolated rat hearts was increased by local ACE inhibitions with ramiprilat. In different models the bradykinin-mediated effects of ACE inhibition were abolished with the specific B2 kinin-receptor antagonist Hoe 140: The cardioprotective effects of ramiprilat or ramipril such as reduction of postischemic reperfusion injuries in isolated rat hearts or the reduction in infarct size in dogs and rabbits were abolished by coadministration of Hoe 140. Furthermore, left ventricular hypertrophy in rats with aortic banding could be prevented or regression was induced when the ACE inhibitor was given in a non-blood pressure-lowering dose. These beneficial effects were also abolished by Hoe 140. In conclusion, in different experimental models, ACE inhibitors exert cardioprotective effects. An enhancement of endothelial autacoid formation (nitric oxide and prostacyclin) by inhibiting degradation of bradykinin may contribute to these effects.", "contents": "Role of bradykinin in the cardiac effects of angiotensin-converting enzyme inhibitors. Angiotensin-converting enzyme (ACE) inhibitors exert their beneficial effects not only via endocrine mechanisms, but most probably also via interference with autocrine-paracrine actions involving local renin-angiotensin and kallikrein-kinin systems with subsequent autacoid release. Inhibition of ACE (kininase II) results in the reduction of angiotensin II generation and kinin degradation, leading to beneficial cardiovascular effects. Bradykinin and prostacyclin release from isolated rat hearts was increased by local ACE inhibitions with ramiprilat. In different models the bradykinin-mediated effects of ACE inhibition were abolished with the specific B2 kinin-receptor antagonist Hoe 140: The cardioprotective effects of ramiprilat or ramipril such as reduction of postischemic reperfusion injuries in isolated rat hearts or the reduction in infarct size in dogs and rabbits were abolished by coadministration of Hoe 140. Furthermore, left ventricular hypertrophy in rats with aortic banding could be prevented or regression was induced when the ACE inhibitor was given in a non-blood pressure-lowering dose. These beneficial effects were also abolished by Hoe 140. In conclusion, in different experimental models, ACE inhibitors exert cardioprotective effects. An enhancement of endothelial autacoid formation (nitric oxide and prostacyclin) by inhibiting degradation of bradykinin may contribute to these effects."} {"id": "PMID:1282636", "title": "Endothelium-dependent relaxations are augmented in rats chronically treated with the angiotensin-converting enzyme inhibitor enalapril.", "content": "The study was designed to evaluate the effects of chronic inhibition of angiotensin-converting enzyme (ACE) on the reactivity of the endothelium and the smooth muscle to vasoconstrictor and vasodilator stimuli in normal rats. Male rats were treated orally for 6 weeks with enalapril (10 mg/kg/day, n = 10) or with placebo (n = 10). Endothelium-dependent relaxations to acetylcholine and adenosine diphosphate were augmented in aortic rings from rats treated with enalapril compared with controls, whereas the response to the endothelium-independent vasodilator SIN-1 were similar. Contractions induced by phenylephrine and angiotensin II remained unchanged. Thus, the results suggest that chronic ACE inhibition enhances the release of relaxing factors from the endothelium in normotensive rats.", "contents": "Endothelium-dependent relaxations are augmented in rats chronically treated with the angiotensin-converting enzyme inhibitor enalapril. The study was designed to evaluate the effects of chronic inhibition of angiotensin-converting enzyme (ACE) on the reactivity of the endothelium and the smooth muscle to vasoconstrictor and vasodilator stimuli in normal rats. Male rats were treated orally for 6 weeks with enalapril (10 mg/kg/day, n = 10) or with placebo (n = 10). Endothelium-dependent relaxations to acetylcholine and adenosine diphosphate were augmented in aortic rings from rats treated with enalapril compared with controls, whereas the response to the endothelium-independent vasodilator SIN-1 were similar. Contractions induced by phenylephrine and angiotensin II remained unchanged. Thus, the results suggest that chronic ACE inhibition enhances the release of relaxing factors from the endothelium in normotensive rats."} {"id": "PMID:1282637", "title": "Role of bradykinin in chronic antihypertensive actions of ramipril in different hypertension models.", "content": "We investigated the chronic effect of bradykinin B2-receptor blockade on the antihypertensive actions of the angiotensin-converting enzyme (ACE) inhibitor ramipril in three different hypertensive rat models, the two-kidney/one-clip (2K1C) hypertensive Wistar rat, the kinin-deficient 2K1C hypertensive Brown Norway Katholieke (BN-K) rat, and the spontaneously hypertensive rat (SHR). Chronic blockade of bradykinin B2 receptors by subcutaneous infusion of the new bradykinin antagonist HOE 140 (500 micrograms/kg/day) attenuated the antihypertensive effect of ramipril only in 2K1C hypertensive Wistar rats, but not in 2K1C BN-K rats and SHR. Our data demonstrate for the first time that potentiation of endogenous kinins contributes to chronic antihypertensive actions of ACE inhibitors in experimental renal hypertension. Whether this holds also true for other forms of hypertension remains to be answered.", "contents": "Role of bradykinin in chronic antihypertensive actions of ramipril in different hypertension models. We investigated the chronic effect of bradykinin B2-receptor blockade on the antihypertensive actions of the angiotensin-converting enzyme (ACE) inhibitor ramipril in three different hypertensive rat models, the two-kidney/one-clip (2K1C) hypertensive Wistar rat, the kinin-deficient 2K1C hypertensive Brown Norway Katholieke (BN-K) rat, and the spontaneously hypertensive rat (SHR). Chronic blockade of bradykinin B2 receptors by subcutaneous infusion of the new bradykinin antagonist HOE 140 (500 micrograms/kg/day) attenuated the antihypertensive effect of ramipril only in 2K1C hypertensive Wistar rats, but not in 2K1C BN-K rats and SHR. Our data demonstrate for the first time that potentiation of endogenous kinins contributes to chronic antihypertensive actions of ACE inhibitors in experimental renal hypertension. Whether this holds also true for other forms of hypertension remains to be answered."} {"id": "PMID:1282638", "title": "[Economic evaluation of prophylaxis with recombinant granulopoiesis stimulating factor].", "content": "The aim of the study was to economically evaluate the prophylactic use of the recombinant factor of the stimulation of granulocyte colonies (rG-CSF) for the prevention of episodes of febrile neutropenia (EFN) following antineoplasic chemotherapy. The methods of economic evaluation used were those of cost analysis and cost-effectivity analysis. The probability of occurence of EFN was estimated by the application of the Delphi method and the costs were calculated. The costs of EFN for the patients with solid tumors is situated between 236,000-377,000 pesetas according to hospitalary centers. For patients with acute leukemia the value was estimated as between 391,000-667,000 pesetas. The results of the cost analysis indicate that the net cost per patient prophylactically treated is between 4,000-64,000 pesetas. The results of the cost-effectivity analysis indicate that the cost per case of no incidence of EFN is between 20,000-320,000 pesetas. Episodes of febrile neutropenia carry expansive hospital and antibiotic clinical treatment. The prophylactic use of new medication for patients between the first and second cycle of chemotherapy, in agreement with the estimates calculated, does not save health care costs but may improve the quality of life in these patients and permit the continuation of a therapeutic schedule without interruption which may improve the life expectancy of the patient.", "contents": "[Economic evaluation of prophylaxis with recombinant granulopoiesis stimulating factor]. The aim of the study was to economically evaluate the prophylactic use of the recombinant factor of the stimulation of granulocyte colonies (rG-CSF) for the prevention of episodes of febrile neutropenia (EFN) following antineoplasic chemotherapy. The methods of economic evaluation used were those of cost analysis and cost-effectivity analysis. The probability of occurence of EFN was estimated by the application of the Delphi method and the costs were calculated. The costs of EFN for the patients with solid tumors is situated between 236,000-377,000 pesetas according to hospitalary centers. For patients with acute leukemia the value was estimated as between 391,000-667,000 pesetas. The results of the cost analysis indicate that the net cost per patient prophylactically treated is between 4,000-64,000 pesetas. The results of the cost-effectivity analysis indicate that the cost per case of no incidence of EFN is between 20,000-320,000 pesetas. Episodes of febrile neutropenia carry expansive hospital and antibiotic clinical treatment. The prophylactic use of new medication for patients between the first and second cycle of chemotherapy, in agreement with the estimates calculated, does not save health care costs but may improve the quality of life in these patients and permit the continuation of a therapeutic schedule without interruption which may improve the life expectancy of the patient."} {"id": "PMID:1282641", "title": "[Somatostatin in preoperative therapy and postoperative diagnosis of a patient with Verner Morrison syndrome].", "content": "We report the case of a patient with Verner-Morrison syndrome due to a malignant MEN I-associated vipoma. Marked tumor-associated hypercalcemia could be treated successfully with somatostatin analogues prior to surgical therapy of the pancreatic tumor. Sixteen months after extirpation of the primary tumor recurrent tumor growth was diagnosed; at this time the patient was clinically asymptomatic and had no abnormal laboratory test results. Liver metastases and local metastases were identified using somatostatin receptor scintigraphy. We report and discuss the use of somatostatin in the treatment of tumor-associated symptoms in endocrine tumors and the possibility of identifying endocrine tumors by means of somatostatin receptor scintigraphy.", "contents": "[Somatostatin in preoperative therapy and postoperative diagnosis of a patient with Verner Morrison syndrome]. We report the case of a patient with Verner-Morrison syndrome due to a malignant MEN I-associated vipoma. Marked tumor-associated hypercalcemia could be treated successfully with somatostatin analogues prior to surgical therapy of the pancreatic tumor. Sixteen months after extirpation of the primary tumor recurrent tumor growth was diagnosed; at this time the patient was clinically asymptomatic and had no abnormal laboratory test results. Liver metastases and local metastases were identified using somatostatin receptor scintigraphy. We report and discuss the use of somatostatin in the treatment of tumor-associated symptoms in endocrine tumors and the possibility of identifying endocrine tumors by means of somatostatin receptor scintigraphy."} {"id": "PMID:1282642", "title": "The gal locus from Haemophilus influenzae: cloning, sequencing and the use of gal mutants to study lipopolysaccharide.", "content": "The gal locus from Haemophilus influenzae was cloned and sequenced. Four genes were identified by amino acid homology: galT, galK, galM and galR. The coding direction of galT, galK and galM is divergent from that of galR. There are non-coding intergenic regions between galR and galT, galT nd galK, and galK and galM. Deletion-insertion mutations constructed in galK and galE, which is in lic3, were moved into the H. influenzae chromosome generating each of the single mutants as well as the double gal mutant. Even when grown on complex media, the double mutant failed to react with an anti-lipopolysaccharide monoclonal antibody known to react with a digalactoside epitope. Both the galE single and the galE galK double mutants were serum-sensitive and relatively avirulent in infant rats, indicating a critical role for galactose metabolism, and providing evidence to support a central role for lipopolysaccharide, in H. influenzae virulence.", "contents": "The gal locus from Haemophilus influenzae: cloning, sequencing and the use of gal mutants to study lipopolysaccharide. The gal locus from Haemophilus influenzae was cloned and sequenced. Four genes were identified by amino acid homology: galT, galK, galM and galR. The coding direction of galT, galK and galM is divergent from that of galR. There are non-coding intergenic regions between galR and galT, galT nd galK, and galK and galM. Deletion-insertion mutations constructed in galK and galE, which is in lic3, were moved into the H. influenzae chromosome generating each of the single mutants as well as the double gal mutant. Even when grown on complex media, the double mutant failed to react with an anti-lipopolysaccharide monoclonal antibody known to react with a digalactoside epitope. Both the galE single and the galE galK double mutants were serum-sensitive and relatively avirulent in infant rats, indicating a critical role for galactose metabolism, and providing evidence to support a central role for lipopolysaccharide, in H. influenzae virulence."} {"id": "PMID:1282649", "title": "Comparative studies on binding of vitronectin and fibronectin to groups A and C streptococci.", "content": "Binding of 125I-labelled fibronectin and vitronectin to streptococci of group A (S. pyogenes), group B (S. agalactiae) and group C (S. dysgalactiae and S. zooepidemicus) isolated from various human infections and bovine mastitis, and S. uberis bovine isolates, was studied. Binding of vitronectin and fibronectin was common among both human groups A and C, and bovine group C streptococci. S. agalactiae strains of human and bovine origin as well as S. uberis bovine isolates bound low levels of both proteins. The binding of radiolabelled fibronectin and vitronectin to selected groups A and C streptococcal strains was specific, time-dependent and occurred with both live and heat-killed (80 degrees C for 15 min) cells. Binding declined rapidly after treatment of cells with trypsin or proteinase K, while pepsin digestion at pH 5.5 affected vitronectin but not fibronectin binding.", "contents": "Comparative studies on binding of vitronectin and fibronectin to groups A and C streptococci. Binding of 125I-labelled fibronectin and vitronectin to streptococci of group A (S. pyogenes), group B (S. agalactiae) and group C (S. dysgalactiae and S. zooepidemicus) isolated from various human infections and bovine mastitis, and S. uberis bovine isolates, was studied. Binding of vitronectin and fibronectin was common among both human groups A and C, and bovine group C streptococci. S. agalactiae strains of human and bovine origin as well as S. uberis bovine isolates bound low levels of both proteins. The binding of radiolabelled fibronectin and vitronectin to selected groups A and C streptococcal strains was specific, time-dependent and occurred with both live and heat-killed (80 degrees C for 15 min) cells. Binding declined rapidly after treatment of cells with trypsin or proteinase K, while pepsin digestion at pH 5.5 affected vitronectin but not fibronectin binding."} {"id": "PMID:1282650", "title": "Detection and purification of a potential precursor protein or a prohaemolysin produced by Staphylococcus haemolyticus.", "content": "The haemolytic substance H7 produced by Staphylococcus haemolyticus is composed of three peptides out of 44 amino acid residues each having a structure resembling a signal peptide. The cytoplasmic fraction for the presence of a protein precursor containing this signal sequence was investigated. Specific rabbit IgGs to substance H7 were isolated by affinity chromatography on Sepharose-4B-H7. These anti-H7 IgGs recognized mainly a 51 kD protein in the cytoplasmic fraction of S. haemolyticus from 2, 4, 6, 8, 10 and 23 h cultures. These results support the idea that the 51 kD protein could be either a prohaemolysin or else the precursor of a protein of unknown function with a signal sequence showing homology with the haemolytic peptides. After affinity chromatography on Sepharose-4B-anti-H7, the 51 kD protein was shown associated with an RNA-protein complex composed of four or five proteins and an RNA estimated at 300 nt. This complex could be associated with the machinery of protein secretion. The 51 kD protein was finally purified to homogeneity by HPLC on a Protein Pak DEAE-5PW column in the presence of 5 M urea.", "contents": "Detection and purification of a potential precursor protein or a prohaemolysin produced by Staphylococcus haemolyticus. The haemolytic substance H7 produced by Staphylococcus haemolyticus is composed of three peptides out of 44 amino acid residues each having a structure resembling a signal peptide. The cytoplasmic fraction for the presence of a protein precursor containing this signal sequence was investigated. Specific rabbit IgGs to substance H7 were isolated by affinity chromatography on Sepharose-4B-H7. These anti-H7 IgGs recognized mainly a 51 kD protein in the cytoplasmic fraction of S. haemolyticus from 2, 4, 6, 8, 10 and 23 h cultures. These results support the idea that the 51 kD protein could be either a prohaemolysin or else the precursor of a protein of unknown function with a signal sequence showing homology with the haemolytic peptides. After affinity chromatography on Sepharose-4B-anti-H7, the 51 kD protein was shown associated with an RNA-protein complex composed of four or five proteins and an RNA estimated at 300 nt. This complex could be associated with the machinery of protein secretion. The 51 kD protein was finally purified to homogeneity by HPLC on a Protein Pak DEAE-5PW column in the presence of 5 M urea."} {"id": "PMID:1282651", "title": "Epidermal growth factor receptor at endothelial cell and pericyte interdigitation in human granulation tissue.", "content": "Angiogenic immature capillaries in human granulation tissue possess many cytoplasmic interdigitations between endothelial cells and pericytes (CIDEP). Epidermal growth factor (EGF) is a potent mitogenic polypeptide which accelerates angiogenesis in vivo and in vitro. We have recently demonstrated in immature capillaries that EGF is present at the CIDEP and proposed that the CIDEP may be involved in a signaling pathway for EGF (Wakui et al., 1990c. Microvasc. Res. 40, 285-291). This study follows that previous report. In the present study, I have investigated the ultrastructural localization of the EGF receptor (EGF-r) at CIDEP. Immunoreactivity for the EGF-r in immature capillaries was located strictly at the CIDEP in large numbers, at the coated pits and vesicles of endothelial cells, and at some lysosome-like structures of the endothelial cells and the pericytes. On the other hand, immunoreactivity for EGF-r was absent in mature capillaries. At the CIDEP, EGF-r immunoreactivity was present at the cell membrane and a few cytoplasmic elements at the tip of pericyte cytoplasmic projections, but it was completely absent at the corresponding endothelial membrane indentation. The present results support our proposed hypothesis that the CIDEP in immature capillaries act as a pathway for EGF transportation from the endothelial cell to the pericyte by a receptor-mediated process.", "contents": "Epidermal growth factor receptor at endothelial cell and pericyte interdigitation in human granulation tissue. Angiogenic immature capillaries in human granulation tissue possess many cytoplasmic interdigitations between endothelial cells and pericytes (CIDEP). Epidermal growth factor (EGF) is a potent mitogenic polypeptide which accelerates angiogenesis in vivo and in vitro. We have recently demonstrated in immature capillaries that EGF is present at the CIDEP and proposed that the CIDEP may be involved in a signaling pathway for EGF (Wakui et al., 1990c. Microvasc. Res. 40, 285-291). This study follows that previous report. In the present study, I have investigated the ultrastructural localization of the EGF receptor (EGF-r) at CIDEP. Immunoreactivity for the EGF-r in immature capillaries was located strictly at the CIDEP in large numbers, at the coated pits and vesicles of endothelial cells, and at some lysosome-like structures of the endothelial cells and the pericytes. On the other hand, immunoreactivity for EGF-r was absent in mature capillaries. At the CIDEP, EGF-r immunoreactivity was present at the cell membrane and a few cytoplasmic elements at the tip of pericyte cytoplasmic projections, but it was completely absent at the corresponding endothelial membrane indentation. The present results support our proposed hypothesis that the CIDEP in immature capillaries act as a pathway for EGF transportation from the endothelial cell to the pericyte by a receptor-mediated process."} {"id": "PMID:1282652", "title": "Possible mechanism(s) for permeability recovery of venules during histamine application.", "content": "Histamine is known to cause a substantial increase in the permeability of venules to both water and proteins. However, this increase is transient, i.e., the initially elevated permeability returns toward control levels, or \"recovers,\" even during continuous histamine stimulation. In this investigation, we attempted to identify the possible chemical signal(s) initiating the permeability recovery process in single venules of rat mesentery. Specifically, we tested whether histamine's binding to H2 receptors and/or the production of prostacyclin by endothelial cells was involved in this process. To achieve this aim, the time course of endothelial cells was involved in this process. To achieve this aim, the time course of histamine-induced changes in permeability to alpha-lactalbumin was measured in the presence of H2 receptor antagonist (cimetidine) or of prostacyclin synthetase inhibitor (tranylcypromine), respectively. Permeability of individually perfused microvessels was measured using fluorescence microscopy. The results demonstrated that permeability recovery was not affected by the H2 receptor antagonist but was suppressed or even abolished by the prostacyclin synthesis inhibitor. Therefore, these results suggest that the production of prostacyclin by endothelial cells might serve as one chemical signal to initiate the permeability recovery process, whereas histamine's binding to H2 receptors is not involved in this phenomenon.", "contents": "Possible mechanism(s) for permeability recovery of venules during histamine application. Histamine is known to cause a substantial increase in the permeability of venules to both water and proteins. However, this increase is transient, i.e., the initially elevated permeability returns toward control levels, or \"recovers,\" even during continuous histamine stimulation. In this investigation, we attempted to identify the possible chemical signal(s) initiating the permeability recovery process in single venules of rat mesentery. Specifically, we tested whether histamine's binding to H2 receptors and/or the production of prostacyclin by endothelial cells was involved in this process. To achieve this aim, the time course of endothelial cells was involved in this process. To achieve this aim, the time course of histamine-induced changes in permeability to alpha-lactalbumin was measured in the presence of H2 receptor antagonist (cimetidine) or of prostacyclin synthetase inhibitor (tranylcypromine), respectively. Permeability of individually perfused microvessels was measured using fluorescence microscopy. The results demonstrated that permeability recovery was not affected by the H2 receptor antagonist but was suppressed or even abolished by the prostacyclin synthesis inhibitor. Therefore, these results suggest that the production of prostacyclin by endothelial cells might serve as one chemical signal to initiate the permeability recovery process, whereas histamine's binding to H2 receptors is not involved in this phenomenon."} {"id": "PMID:1282653", "title": "Mechanisms of augmented resistance of cyclosporin A-treated mice to influenza virus infection by trehalose-6,6'-dimycolate.", "content": "Cyclosporin A (CsA), which is an immunosuppressive drug of helper T lymphocytes, diminished a resistance of mice to influenza virus infection. Mice inoculated intravenously with trehalose-6,6'-dimycolate (TDM, a glycolipid component of the cell wall of Mycobacterium) in an oil-in-water emulsion (TDM emulsion) recovered the resistance to influenza virus infection impaired by CsA. Number of antibody-producing cells was markedly reduced in CsA- and/or TDM-treated mice. Interferon production in lung of TDM-treated mice was augmented; however, it was extremely reduced not only in CsA-treated mice, but also in CsA- and TDM-treated mice. Activities of natural killer cells of CsA- and/or TDM-treated mice were not different from that of control mice. Numbers of lymphocytes in lung of TDM-treated mice and CsA- and TDM-treated mice were more predominantly increased than that of control mice. Analysis of lung lymphocytes by flow cytometry revealed no difference between the populations of L3T4+ T lymphocytes and Lyt-2.2+ T lymphocytes in CsA- and/or TDM-treated mice and the populations in control mice. However, the population of gamma delta T cell receptor positive (gamma delta TCR+) lymphocytes increased markedly in lung of TDM-treated mice and also CsA- and TDM-treated mice. In vitro experiments showed that macrophage cultures treated with TDM emulsion released a mediator(s) which activates T lymphocytes, but not B lymphocytes. These and our earlier results suggest that the recovered anti-influenza virus resistance of CsA-treated mice by treatment with TDM emulsion was caused by elicitation of macrophages with TDM, then activation of T lymphocytes, especially gamma delta TCR+ lymphocytes.", "contents": "Mechanisms of augmented resistance of cyclosporin A-treated mice to influenza virus infection by trehalose-6,6'-dimycolate. Cyclosporin A (CsA), which is an immunosuppressive drug of helper T lymphocytes, diminished a resistance of mice to influenza virus infection. Mice inoculated intravenously with trehalose-6,6'-dimycolate (TDM, a glycolipid component of the cell wall of Mycobacterium) in an oil-in-water emulsion (TDM emulsion) recovered the resistance to influenza virus infection impaired by CsA. Number of antibody-producing cells was markedly reduced in CsA- and/or TDM-treated mice. Interferon production in lung of TDM-treated mice was augmented; however, it was extremely reduced not only in CsA-treated mice, but also in CsA- and TDM-treated mice. Activities of natural killer cells of CsA- and/or TDM-treated mice were not different from that of control mice. Numbers of lymphocytes in lung of TDM-treated mice and CsA- and TDM-treated mice were more predominantly increased than that of control mice. Analysis of lung lymphocytes by flow cytometry revealed no difference between the populations of L3T4+ T lymphocytes and Lyt-2.2+ T lymphocytes in CsA- and/or TDM-treated mice and the populations in control mice. However, the population of gamma delta T cell receptor positive (gamma delta TCR+) lymphocytes increased markedly in lung of TDM-treated mice and also CsA- and TDM-treated mice. In vitro experiments showed that macrophage cultures treated with TDM emulsion released a mediator(s) which activates T lymphocytes, but not B lymphocytes. These and our earlier results suggest that the recovered anti-influenza virus resistance of CsA-treated mice by treatment with TDM emulsion was caused by elicitation of macrophages with TDM, then activation of T lymphocytes, especially gamma delta TCR+ lymphocytes."} {"id": "PMID:1282654", "title": "Demonstration of low molecular weight polypeptides associated with small, round-structured viruses by western immunoblot analysis.", "content": "Small, round-structured viruses (SRSV) were detected in 14 of 300 fecal specimens obtained from patients with acute gastroenteritis by electron microscopy. These SRSV strains were morphologically indistinguishable from one another. While 11 of these strains had a single usual major structural protein with molecular weight of 63,000 (63K) daltons (p63), interestingly, three strains possessed a single major structural protein with molecular weight of 33K daltons (p33). Treatments of p63-SRSV with proteolytic enzymes or denaturating reagents did not affect the molecular weight of p63, and the p33 was not detectable by Western immunoblot in the ultracentrifugal supernatant of the p63-SRSV suspension. These results suggest that the p33 is neither a definitive subunit of p63 nor disintegrated component derived from the p63-SRSV but a novel polypeptide of SRSV. Immune electron microscopy and Western immunoblot analyses indicated that p63- and p33-SRSVs may share an antigenic determinant(s).", "contents": "Demonstration of low molecular weight polypeptides associated with small, round-structured viruses by western immunoblot analysis. Small, round-structured viruses (SRSV) were detected in 14 of 300 fecal specimens obtained from patients with acute gastroenteritis by electron microscopy. These SRSV strains were morphologically indistinguishable from one another. While 11 of these strains had a single usual major structural protein with molecular weight of 63,000 (63K) daltons (p63), interestingly, three strains possessed a single major structural protein with molecular weight of 33K daltons (p33). Treatments of p63-SRSV with proteolytic enzymes or denaturating reagents did not affect the molecular weight of p63, and the p33 was not detectable by Western immunoblot in the ultracentrifugal supernatant of the p63-SRSV suspension. These results suggest that the p33 is neither a definitive subunit of p63 nor disintegrated component derived from the p63-SRSV but a novel polypeptide of SRSV. Immune electron microscopy and Western immunoblot analyses indicated that p63- and p33-SRSVs may share an antigenic determinant(s)."} {"id": "PMID:1282655", "title": "Outcome of paediatric bacterial meningitis 1979-1989.", "content": "To determine the outcome of all cases of paediatric bacterial meningitis over the 11-year period 1979-1989 and discuss the role of adjunctive therapy with dexamethasone. The study was performed by retrospective case review at Flinders Medical Centre, a general teaching hospital. There were 80 episodes in 79 patients. The age range was 2 days to 15 years (mean, 1.7 years). Haemophilus influenzae type b was the commonest organism (60 of 80 cases; 75%). There were five deaths (6.3%). Sensorineural hearing loss was found in six of 71 children (8.5%) and was bilateral and severe in four (5.6%). Other problems included learning difficulties (12.7%), motor problems (7%), speech delay (7%), hyperactivity (4.2%), blindness (2.8%), obstructive hydrocephalus (2.8%) and recurrent seizures (2.8%). Bacterial meningitis remains a disease with significant morbidity and mortality. Adjunctive therapy with dexamethasone should be considered, and vaccination against Haemophilus influenzae type b should be routine.", "contents": "Outcome of paediatric bacterial meningitis 1979-1989. To determine the outcome of all cases of paediatric bacterial meningitis over the 11-year period 1979-1989 and discuss the role of adjunctive therapy with dexamethasone. The study was performed by retrospective case review at Flinders Medical Centre, a general teaching hospital. There were 80 episodes in 79 patients. The age range was 2 days to 15 years (mean, 1.7 years). Haemophilus influenzae type b was the commonest organism (60 of 80 cases; 75%). There were five deaths (6.3%). Sensorineural hearing loss was found in six of 71 children (8.5%) and was bilateral and severe in four (5.6%). Other problems included learning difficulties (12.7%), motor problems (7%), speech delay (7%), hyperactivity (4.2%), blindness (2.8%), obstructive hydrocephalus (2.8%) and recurrent seizures (2.8%). Bacterial meningitis remains a disease with significant morbidity and mortality. Adjunctive therapy with dexamethasone should be considered, and vaccination against Haemophilus influenzae type b should be routine."} {"id": "PMID:1282656", "title": "High dose chemotherapy and autologous bone marrow transplantation in advanced Hodgkin's disease.", "content": "To present the use of high dose chemotherapy with autologous bone marrow transplantation as salvage therapy for advanced Hodgkin's disease in Australia. A prospective open study for patients whose disease was resistant to conventional treatment. The bone marrow transplantation units of four Australian tertiary hospitals. Seventeen patients (median age 30 years) entered and completed the study. The stage of the disease at initial diagnosis was I or II (seven patients), III (seven patients) and IV (three patients). Histological types were lymphocyte predominant (one), nodular sclerosis (12), mixed cellularity (three) and unknown (one). Therapy before consideration for transplantation included radiotherapy (13), mustine, vincristine, procarbazine and prednisone (MOPP--17 patients) or doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD--13 patients) and other chemotherapy regimens (five). The median interval from diagnosis to transplantation was 29 months (range, 9-178 months). The patient's disease was classified as sensitive (nine) or resistant (eight) to treatment, depending on the response to the most recent course of chemotherapy. Morphologically normal autologous bone marrow was harvested and cryopreserved. The conditioning regimen given was cyclophosphamide, carmustine and etoposide (14) or busulphan and cyclophosphamide (three). The marrow was then infused. Remission (complete or partial), disease-free survival and overall survival. Over all, 10 of 17 patients (59%) entered or remained in complete remission and four of 17 (24%) achieved partial remission. The overall actuarial survival at 30 months was 70%. Eight of the nine patients with treatment-sensitive disease (89%) remain disease-free at a median of 22 months (range, 18-29 months) after transplantation. Two of the eight patients with resistant disease (25%) are disease-free at 20 and 28 months. There was one procedure-related death from haemorrhage and four disease-related deaths at six, seven, eight and 13 months after transplantation. Autologous bone marrow transplantation may provide an effective salvage therapy in advanced Hodgkin's disease, particularly for patients with treatment-sensitive disease and a low tumour burden.", "contents": "High dose chemotherapy and autologous bone marrow transplantation in advanced Hodgkin's disease. To present the use of high dose chemotherapy with autologous bone marrow transplantation as salvage therapy for advanced Hodgkin's disease in Australia. A prospective open study for patients whose disease was resistant to conventional treatment. The bone marrow transplantation units of four Australian tertiary hospitals. Seventeen patients (median age 30 years) entered and completed the study. The stage of the disease at initial diagnosis was I or II (seven patients), III (seven patients) and IV (three patients). Histological types were lymphocyte predominant (one), nodular sclerosis (12), mixed cellularity (three) and unknown (one). Therapy before consideration for transplantation included radiotherapy (13), mustine, vincristine, procarbazine and prednisone (MOPP--17 patients) or doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD--13 patients) and other chemotherapy regimens (five). The median interval from diagnosis to transplantation was 29 months (range, 9-178 months). The patient's disease was classified as sensitive (nine) or resistant (eight) to treatment, depending on the response to the most recent course of chemotherapy. Morphologically normal autologous bone marrow was harvested and cryopreserved. The conditioning regimen given was cyclophosphamide, carmustine and etoposide (14) or busulphan and cyclophosphamide (three). The marrow was then infused. Remission (complete or partial), disease-free survival and overall survival. Over all, 10 of 17 patients (59%) entered or remained in complete remission and four of 17 (24%) achieved partial remission. The overall actuarial survival at 30 months was 70%. Eight of the nine patients with treatment-sensitive disease (89%) remain disease-free at a median of 22 months (range, 18-29 months) after transplantation. Two of the eight patients with resistant disease (25%) are disease-free at 20 and 28 months. There was one procedure-related death from haemorrhage and four disease-related deaths at six, seven, eight and 13 months after transplantation. Autologous bone marrow transplantation may provide an effective salvage therapy in advanced Hodgkin's disease, particularly for patients with treatment-sensitive disease and a low tumour burden."} {"id": "PMID:1282660", "title": "Signal transduction via the fibronectin receptor: do integrins regulate matrix remodeling?", "content": "An appropriate balance of matrix synthesis and degradation is required for normal morphogenesis and maintenance of tissue architecture. Extracellular matrix molecules and their receptors, as well as proteinases and their inhibitors, are all involved in matrix remodeling. This report examines the idea that extracellular matrix receptors can regulate matrix remodeling. Rabbit synovial fibroblasts and human embryonic lung fibroblasts (MRC-5) were cultured under two sets of conditions. First, they were plated in serum and allowed to establish an extracellular matrix over a 48 h period. Rat monoclonal antibody to the alpha 5/beta 1 integrin fibronectin receptor or normal rat IgG was added to the medium and the expression of the metalloproteinases was examined. Cells treated with anti-alpha 5/beta 1 expressed procollagenase and prostromelysin, whereas the control cells did not. In both cases the cells were well spread and maintained a well-organized cytoskeleton. In the second condition, cells were plated in serum-free medium on intact fibronectin, anti-alpha 5/beta 1, or fragments of fibronectin that contained the cell-binding domain. Cells attached and spread on all these substrates in a fibronectin receptor-dependent manner. They expressed collagenase and stromelysin on anti-alpha 5/beta 1 and on several fibronectin fragments, but not on intact fibronectin. These data support the hypothesis that the fibronectin receptor can exist in more than one functional state and that these functional states provide information that influences gene expression. Adhesion and spreading are supported by all states, whereas only a subset permits collagenase and stromelysin expression.", "contents": "Signal transduction via the fibronectin receptor: do integrins regulate matrix remodeling? An appropriate balance of matrix synthesis and degradation is required for normal morphogenesis and maintenance of tissue architecture. Extracellular matrix molecules and their receptors, as well as proteinases and their inhibitors, are all involved in matrix remodeling. This report examines the idea that extracellular matrix receptors can regulate matrix remodeling. Rabbit synovial fibroblasts and human embryonic lung fibroblasts (MRC-5) were cultured under two sets of conditions. First, they were plated in serum and allowed to establish an extracellular matrix over a 48 h period. Rat monoclonal antibody to the alpha 5/beta 1 integrin fibronectin receptor or normal rat IgG was added to the medium and the expression of the metalloproteinases was examined. Cells treated with anti-alpha 5/beta 1 expressed procollagenase and prostromelysin, whereas the control cells did not. In both cases the cells were well spread and maintained a well-organized cytoskeleton. In the second condition, cells were plated in serum-free medium on intact fibronectin, anti-alpha 5/beta 1, or fragments of fibronectin that contained the cell-binding domain. Cells attached and spread on all these substrates in a fibronectin receptor-dependent manner. They expressed collagenase and stromelysin on anti-alpha 5/beta 1 and on several fibronectin fragments, but not on intact fibronectin. These data support the hypothesis that the fibronectin receptor can exist in more than one functional state and that these functional states provide information that influences gene expression. Adhesion and spreading are supported by all states, whereas only a subset permits collagenase and stromelysin expression."} {"id": "PMID:1282661", "title": "Localization of cleavage sites for human fibroblast collagenase in the bait region of five mammalian alpha-macroglobulins.", "content": "The interaction between human fibroblast collagenase and five mammalian alpha-macroglobulins (human alpha 2-macroglobulin and pregnancy zone protein, rat alpha 1- and alpha 2-macroglobulin and rat alpha 1-inhibitor 3) is discussed. Complex formation involves specific limited proteolysis in the alpha-macroglobulin bait regions, activation of the internal beta-cysteinyl-gamma-glutamyl thiol esters, conformational changes and covalent complex formation. For human alpha 2-macroglobulin, and rat alpha 1-macroglobulin and alpha 2-macroglobulin it is estimated that the overall rate constant of complex formation is greater than 1.10(6) M-1s-1, while it is much lower for human pregnancy zone protein and rat alpha 1-inhibitor 3. More than 95% of the complexed collagenase is covalently bound. The identification of the sites of specific limited proteolysis in the bait regions of the five alpha-macroglobulins shows that cleavage may take place in sequences that are not related to those identified earlier in the collagens. These results greatly expand the repertoire of sequences known to be cleaved by fibroblast collagenase, and suggest that this proteinase has a primary substrate specificity resembling that of the microbial proteinase thermolysin as it preferentially cleaves at the NH2-terminal side of large hydrophobic residues. In addition, the results highlight the unique structure of the flexible alpha-macroglobulin bait region in that it can accommodate a conformation required by the highly restrictive fibroblasts collagenase. It is suggested that alpha-macroglobulins may play an important role in locally controlling the activity of collagenases and perhaps other proteinases of the extracellular matrix.", "contents": "Localization of cleavage sites for human fibroblast collagenase in the bait region of five mammalian alpha-macroglobulins. The interaction between human fibroblast collagenase and five mammalian alpha-macroglobulins (human alpha 2-macroglobulin and pregnancy zone protein, rat alpha 1- and alpha 2-macroglobulin and rat alpha 1-inhibitor 3) is discussed. Complex formation involves specific limited proteolysis in the alpha-macroglobulin bait regions, activation of the internal beta-cysteinyl-gamma-glutamyl thiol esters, conformational changes and covalent complex formation. For human alpha 2-macroglobulin, and rat alpha 1-macroglobulin and alpha 2-macroglobulin it is estimated that the overall rate constant of complex formation is greater than 1.10(6) M-1s-1, while it is much lower for human pregnancy zone protein and rat alpha 1-inhibitor 3. More than 95% of the complexed collagenase is covalently bound. The identification of the sites of specific limited proteolysis in the bait regions of the five alpha-macroglobulins shows that cleavage may take place in sequences that are not related to those identified earlier in the collagens. These results greatly expand the repertoire of sequences known to be cleaved by fibroblast collagenase, and suggest that this proteinase has a primary substrate specificity resembling that of the microbial proteinase thermolysin as it preferentially cleaves at the NH2-terminal side of large hydrophobic residues. In addition, the results highlight the unique structure of the flexible alpha-macroglobulin bait region in that it can accommodate a conformation required by the highly restrictive fibroblasts collagenase. It is suggested that alpha-macroglobulins may play an important role in locally controlling the activity of collagenases and perhaps other proteinases of the extracellular matrix."} {"id": "PMID:1282662", "title": "Cytochromes P450 NMa, NMb (2G1), and LM4 (1A2) are differentially expressed during development in rabbit olfactory mucosa and liver.", "content": "Mammalian olfactory mucosa has a high concentration of cytochrome P450 monooxygenases (P450). The major olfactory P450 isoforms in adult rabbits include P450 NMa, which is found in both olfactory and respiratory mucosa, as well as in liver at a low level, P450 NMb (2G1), which is olfactory specific, and P450 form 4 (1A2), which is found only in liver and olfactory mucosa. In the present study, we have found that the developmental expression of olfactory P450 in rabbits is not coordinated with the ontogenesis of hepatic P450. These three P450 isoforms were detected immunochemically and found to be at a relatively high level in olfactory but not hepatic microsomes in the first 2 weeks after birth. In the liver, NMb is not detectable at any age and NMa is not detectable until the fourth week. P450 1A2 is not detectable until the third week, but its level increases rapidly in the fourth week. These P450 isoforms are also detectable in prenatal olfactory tissue at 2 days before birth, indicating that direct exposure to air is not a prerequisite for their early expression in this tissue and that the early appearance of these enzymes may be controlled by both endogenous and environmental factors. In addition, the developmental expression of 2E1, a minor olfactory P450 isoform, also occurs earlier in olfactory mucosa than in liver, and the same conclusion can be made about the expression of NADPH-P450 reductase, which is detectable in olfactory microsomes but not in hepatic microsomes from prenatal rabbits. Thus, the regulatory mechanisms that control basal prenatal expression in the olfactory tissue may be common for multiple P450 isoforms and perhaps also for other biotransformation enzymes. The tissue-specific early onset of expression of multiple forms of P450 in olfactory tissue suggests that these enzymes may play an important role in the neonatal period, when olfactory ability is vital for the survival of the newborn. The presence of relatively high levels of biotransformation enzymes in the olfactory mucosa may also have important implications for neonatal inhalation toxicology.", "contents": "Cytochromes P450 NMa, NMb (2G1), and LM4 (1A2) are differentially expressed during development in rabbit olfactory mucosa and liver. Mammalian olfactory mucosa has a high concentration of cytochrome P450 monooxygenases (P450). The major olfactory P450 isoforms in adult rabbits include P450 NMa, which is found in both olfactory and respiratory mucosa, as well as in liver at a low level, P450 NMb (2G1), which is olfactory specific, and P450 form 4 (1A2), which is found only in liver and olfactory mucosa. In the present study, we have found that the developmental expression of olfactory P450 in rabbits is not coordinated with the ontogenesis of hepatic P450. These three P450 isoforms were detected immunochemically and found to be at a relatively high level in olfactory but not hepatic microsomes in the first 2 weeks after birth. In the liver, NMb is not detectable at any age and NMa is not detectable until the fourth week. P450 1A2 is not detectable until the third week, but its level increases rapidly in the fourth week. These P450 isoforms are also detectable in prenatal olfactory tissue at 2 days before birth, indicating that direct exposure to air is not a prerequisite for their early expression in this tissue and that the early appearance of these enzymes may be controlled by both endogenous and environmental factors. In addition, the developmental expression of 2E1, a minor olfactory P450 isoform, also occurs earlier in olfactory mucosa than in liver, and the same conclusion can be made about the expression of NADPH-P450 reductase, which is detectable in olfactory microsomes but not in hepatic microsomes from prenatal rabbits. Thus, the regulatory mechanisms that control basal prenatal expression in the olfactory tissue may be common for multiple P450 isoforms and perhaps also for other biotransformation enzymes. The tissue-specific early onset of expression of multiple forms of P450 in olfactory tissue suggests that these enzymes may play an important role in the neonatal period, when olfactory ability is vital for the survival of the newborn. The presence of relatively high levels of biotransformation enzymes in the olfactory mucosa may also have important implications for neonatal inhalation toxicology."} {"id": "PMID:1282663", "title": "Binding kinetics of gamma-aminobutyric acidA receptor noncompetitive antagonists: trioxabicyclooctane, dithiane, and cyclodiene insecticide-induced slow transition to blocked chloride channel conformation.", "content": "Binding kinetics and affinities are determined for 25 antagonists interacting with the noncompetitive blocker site of the gamma-aminobutyric acidA receptor complex present in bovine brain membranes. Four radiolabeled noncompetitive antagonists are 4-tert-butylbicyclophosphoro[35S]thionate ([35S]TBPS), 4-tert-butylbicycloortho[3',4'-3H2]benzoate, 4'-cyano-4-sec-[3,4-3H2]butylbicycloorthobenzoate, and the new 4'-ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate. The other 21 antagonists are unlabeled inhibitors of three chemical classes (other trioxabicyclooctane, dithiane, and cyclodiene insecticides). The radioligands bind to a single noninteracting site in the membranes, based on linear Scatchard plots and monophasic association and dissociation kinetics. The kinetics of unlabeled ligands are estimated by their effect on the [35S]TBPS association curve, using the theoretical model of Motulsky and Mahan [Mol. Pharmacol. 25:1-9 (1984)]. The receptor affinities of trioxabicyclooctanes and dithianes correlate with their association rates, whereas those of cyclodienes correlate with their dissociation rates. The low association rate constants for all ligands (< or = 3 x 10(7) M-1 min-1 at 25 degrees) are consistent with a slow transition to a blocked receptor conformation upon binding of these channel blockers. The association rate-controlled affinity for the trioxabicyclooctanes and dithianes is suggestive of an induced-fit model in which binding of the ligand initiates a conformational change in the receptor complex to the blocked state.", "contents": "Binding kinetics of gamma-aminobutyric acidA receptor noncompetitive antagonists: trioxabicyclooctane, dithiane, and cyclodiene insecticide-induced slow transition to blocked chloride channel conformation. Binding kinetics and affinities are determined for 25 antagonists interacting with the noncompetitive blocker site of the gamma-aminobutyric acidA receptor complex present in bovine brain membranes. Four radiolabeled noncompetitive antagonists are 4-tert-butylbicyclophosphoro[35S]thionate ([35S]TBPS), 4-tert-butylbicycloortho[3',4'-3H2]benzoate, 4'-cyano-4-sec-[3,4-3H2]butylbicycloorthobenzoate, and the new 4'-ethynyl-4-n-[2,3-3H2]propylbicycloorthobenzoate. The other 21 antagonists are unlabeled inhibitors of three chemical classes (other trioxabicyclooctane, dithiane, and cyclodiene insecticides). The radioligands bind to a single noninteracting site in the membranes, based on linear Scatchard plots and monophasic association and dissociation kinetics. The kinetics of unlabeled ligands are estimated by their effect on the [35S]TBPS association curve, using the theoretical model of Motulsky and Mahan [Mol. Pharmacol. 25:1-9 (1984)]. The receptor affinities of trioxabicyclooctanes and dithianes correlate with their association rates, whereas those of cyclodienes correlate with their dissociation rates. The low association rate constants for all ligands (< or = 3 x 10(7) M-1 min-1 at 25 degrees) are consistent with a slow transition to a blocked receptor conformation upon binding of these channel blockers. The association rate-controlled affinity for the trioxabicyclooctanes and dithianes is suggestive of an induced-fit model in which binding of the ligand initiates a conformational change in the receptor complex to the blocked state."} {"id": "PMID:1282664", "title": "Mechanism of anti-human immunodeficiency virus action of polyoxometalates, a class of broad-spectrum antiviral agents.", "content": "Various polyoxometalates proved inhibitory to the replication of a number of enveloped DNA and RNA viruses, i.e., herpesviruses (herpes simplex and cytomegalo), togaviruses (Sindbis), paramyxoviruses (respiratory syncytial), rhabdoviruses (vesicular stomatitis), arenaviruses (Junin and Tacaribe), and retroviruses [human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), simian immunodeficiency virus, and murine sarcoma virus]. The most potent compounds, i.e., JM1590 [K13[Ce(SiW11O39)2]. 26H2O] and JM2766 [K6[BGa(H2O)W11O39]. 15H2O], inhibited HIV-1 and simian immunodeficiency virus at concentrations as low as 0.008-0.8 microM. The polyoxometalates also inhibited giant cell formation in co-cultures of HIV-infected HUT-78 cells and uninfected MOLT-4 cells. Studies designed to unravel the mechanism of action of these compounds revealed that they inhibit the reverse transcriptase activity associated with HIV. The polyoxometalates also proved inhibitory to the binding of HIV-1 virions to the cells. From \"time of addition\" experiments, whereby the polyoxometalates were added at different times after virus infection, their mechanism of anti-HIV action could be attributed to inhibition of virus-cell binding. There was a good correlation (r = 0.84) between the inhibitory effects of the compounds on HIV-1-induced cytopathicity and their inhibitory effects on syncytium formation and a close correlation (r = 0.902) between their inhibitory effects on syncytium formation and their interaction with gp120, whereas there was no correlation between their anti-HIV-1 activity and their inhibitory effects on HIV-1 reverse transcriptase. In flow cytometric studies, the compounds did not interfere with the binding of OKT4A/Leu-3a monoclonal antibody to the CD4 receptor of uninfected cells, but they inhibited binding of anti-gp120 monoclonal antibody to HIV-1-infected cells. Thus, the binding of the polyoxometalates to the viral envelope glycoprotein gp120 is responsible for their anti-HIV activity.", "contents": "Mechanism of anti-human immunodeficiency virus action of polyoxometalates, a class of broad-spectrum antiviral agents. Various polyoxometalates proved inhibitory to the replication of a number of enveloped DNA and RNA viruses, i.e., herpesviruses (herpes simplex and cytomegalo), togaviruses (Sindbis), paramyxoviruses (respiratory syncytial), rhabdoviruses (vesicular stomatitis), arenaviruses (Junin and Tacaribe), and retroviruses [human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2), simian immunodeficiency virus, and murine sarcoma virus]. The most potent compounds, i.e., JM1590 [K13[Ce(SiW11O39)2]. 26H2O] and JM2766 [K6[BGa(H2O)W11O39]. 15H2O], inhibited HIV-1 and simian immunodeficiency virus at concentrations as low as 0.008-0.8 microM. The polyoxometalates also inhibited giant cell formation in co-cultures of HIV-infected HUT-78 cells and uninfected MOLT-4 cells. Studies designed to unravel the mechanism of action of these compounds revealed that they inhibit the reverse transcriptase activity associated with HIV. The polyoxometalates also proved inhibitory to the binding of HIV-1 virions to the cells. From \"time of addition\" experiments, whereby the polyoxometalates were added at different times after virus infection, their mechanism of anti-HIV action could be attributed to inhibition of virus-cell binding. There was a good correlation (r = 0.84) between the inhibitory effects of the compounds on HIV-1-induced cytopathicity and their inhibitory effects on syncytium formation and a close correlation (r = 0.902) between their inhibitory effects on syncytium formation and their interaction with gp120, whereas there was no correlation between their anti-HIV-1 activity and their inhibitory effects on HIV-1 reverse transcriptase. In flow cytometric studies, the compounds did not interfere with the binding of OKT4A/Leu-3a monoclonal antibody to the CD4 receptor of uninfected cells, but they inhibited binding of anti-gp120 monoclonal antibody to HIV-1-infected cells. Thus, the binding of the polyoxometalates to the viral envelope glycoprotein gp120 is responsible for their anti-HIV activity."} {"id": "PMID:1282665", "title": "Effects of a benz[e]indene on gamma-aminobutyric acid-gated chloride currents in cultured postnatal rat hippocampal neurons.", "content": "Benz[e]indenes (BIs) are tricyclic molecules that can be envisioned as steroids without an A-ring. Because certain steroids are known to alter gamma-aminobutyric acid (GABA) responses in central neurons, we examined the effects of a substituted BI resembling 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-OH-DHP) on GABA-gated chloride currents in cultured postnatal rat hippocampal neurons. The compound, BI-1, reversibly potentiated GABA currents at concentrations of > 10 nM, with an EC50 value of 0.2 microM. BI-1 increased the apparent affinity of GABA for its receptor, decreasing the GABA EC50 from 9 microM to 3 microM. BI-1 had no effect on the shape of the GABA current-voltage relationship and did not alter the GABA reversal potential. The effects of BI-1 were not altered by benzodiazepine or picrotoxin site antagonists. At concentrations up to 10 microM, where maximal effects on GABA currents were seen, BI-1 did not directly activate a membrane current. This contrasts with the effects of 3 alpha-OH-DHP, which activated chloride currents at concentrations that were subsaturating for GABA potentiation. These results suggest that the BIs may be useful for determining the mechanisms by which steroids potentiate GABA responses and directly gate chloride channels.", "contents": "Effects of a benz[e]indene on gamma-aminobutyric acid-gated chloride currents in cultured postnatal rat hippocampal neurons. Benz[e]indenes (BIs) are tricyclic molecules that can be envisioned as steroids without an A-ring. Because certain steroids are known to alter gamma-aminobutyric acid (GABA) responses in central neurons, we examined the effects of a substituted BI resembling 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha-OH-DHP) on GABA-gated chloride currents in cultured postnatal rat hippocampal neurons. The compound, BI-1, reversibly potentiated GABA currents at concentrations of > 10 nM, with an EC50 value of 0.2 microM. BI-1 increased the apparent affinity of GABA for its receptor, decreasing the GABA EC50 from 9 microM to 3 microM. BI-1 had no effect on the shape of the GABA current-voltage relationship and did not alter the GABA reversal potential. The effects of BI-1 were not altered by benzodiazepine or picrotoxin site antagonists. At concentrations up to 10 microM, where maximal effects on GABA currents were seen, BI-1 did not directly activate a membrane current. This contrasts with the effects of 3 alpha-OH-DHP, which activated chloride currents at concentrations that were subsaturating for GABA potentiation. These results suggest that the BIs may be useful for determining the mechanisms by which steroids potentiate GABA responses and directly gate chloride channels."} {"id": "PMID:1282666", "title": "Myocardial fatty acid oxidation during ischemia and reperfusion.", "content": "Inhibition of fatty acid oxidation is an early event in myocardial ischemia that most likely contributes to tissue injury by the accumulation of potentially toxic intermediates such as acylCoA and acylcarnitine. After reperfusion both myocardial oxygen consumption and fatty acid oxidation may rapidly recover to preischemic levels, even when contractile function remains depressed. The mechanisms underlying the apparent dissociation between contractile function and oxidative metabolism early during reperfusion are still controversial. In isolated rat hearts subjected to 60 min of no-flow ischemia myocardial oxygen consumption and oxidation of palmitate were lowered during reperfusion by 3 mM of NiCl2 and by 6 microM of ruthenium red. The results provide indirect evidence for the hypothesis that intracellular calcium transport may be involved in the mechanisms responsible for the high oxidative metabolic rate early after reperfusion.", "contents": "Myocardial fatty acid oxidation during ischemia and reperfusion. Inhibition of fatty acid oxidation is an early event in myocardial ischemia that most likely contributes to tissue injury by the accumulation of potentially toxic intermediates such as acylCoA and acylcarnitine. After reperfusion both myocardial oxygen consumption and fatty acid oxidation may rapidly recover to preischemic levels, even when contractile function remains depressed. The mechanisms underlying the apparent dissociation between contractile function and oxidative metabolism early during reperfusion are still controversial. In isolated rat hearts subjected to 60 min of no-flow ischemia myocardial oxygen consumption and oxidation of palmitate were lowered during reperfusion by 3 mM of NiCl2 and by 6 microM of ruthenium red. The results provide indirect evidence for the hypothesis that intracellular calcium transport may be involved in the mechanisms responsible for the high oxidative metabolic rate early after reperfusion."} {"id": "PMID:1282667", "title": "Effects of palmitoyl CoA and palmitoyl carnitine on the membrane potential and Mg2+ content of rat heart mitochondria.", "content": "Palmitoyl CoA and palmitoyl carnitine added to rat heart mitochondria in amounts above 20 and 50 nmoles/mg protein, respectively, induced a fall in transmembrane potential and loss of endogenous Mg2+. The dissipation of membrane potential by low concentrations of palmitoyl CoA in the presence of Ca2+, but not that of high concentrations of palmitoyl CoA alone, was prevented by either ruthenium red, Cyclosporin A or Mg2+, but reversed only by Mg2+. The fall of membrane potential induced by palmitoyl carnitine was not prevented by any of these factors. It is suggested that the action of both palmitoyl CoA and palmitoyl carnitine at high concentrations is due to a non specific disruption of membrane architecture, while that of low concentrations of palmitoyl CoA in the presence of Ca2+ is associated specifically with energy dissipation due to Ca2+ cycling.", "contents": "Effects of palmitoyl CoA and palmitoyl carnitine on the membrane potential and Mg2+ content of rat heart mitochondria. Palmitoyl CoA and palmitoyl carnitine added to rat heart mitochondria in amounts above 20 and 50 nmoles/mg protein, respectively, induced a fall in transmembrane potential and loss of endogenous Mg2+. The dissipation of membrane potential by low concentrations of palmitoyl CoA in the presence of Ca2+, but not that of high concentrations of palmitoyl CoA alone, was prevented by either ruthenium red, Cyclosporin A or Mg2+, but reversed only by Mg2+. The fall of membrane potential induced by palmitoyl carnitine was not prevented by any of these factors. It is suggested that the action of both palmitoyl CoA and palmitoyl carnitine at high concentrations is due to a non specific disruption of membrane architecture, while that of low concentrations of palmitoyl CoA in the presence of Ca2+ is associated specifically with energy dissipation due to Ca2+ cycling."} {"id": "PMID:1282668", "title": "Identification of a gonadotropin-releasing hormone-responsive region in the glycoprotein hormone alpha-subunit promoter.", "content": "Transcriptional regulation of the glycoprotein hormone alpha-subunit gene has been studied extensively in placental cells, but much less is known about its regulation in the pituitary gland. In this study, transcriptional control of the human alpha-subunit gene by GnRH was analyzed using transient expression assays in primary cultures of rat pituitary cells using alpha promoter constructs linked to a luciferase reporter gene. Deletion mutants between -846 and -156 basepairs (bp) had little effect on basal expression, but further deletion to -132 bp reduced basal activity by approximately 50%. Deletion of a cAMP response element between -132 and -99 bp caused a marked loss of basal activity, reducing expression to that of background luciferase activity. The same constructs were analyzed for cAMP responsiveness in primary pituitary cells. The degree of stimulation with 1 mM 8-bromo-cAMP (3.6- to 6.0-fold) was relatively unaffected by deletions from -846 to -132 bp, whereas cAMP stimulation was decreased by further deletion to -99 bp, consistent with the presence of previously defined cAMP response elements in this region of the alpha promoter. GnRH stimulation of alpha promoter activity was highly dependent upon the time of hormone addition after transfection, being most effective when added soon after transfection. Under optimal conditions, GnRH stimulated -846 alpha LUC expression by 20-fold. GnRH responsiveness was retained with deletion to -346 bp, but it was decreased by 55% after deletion to -280 bp and by 79% with deletion to -244 bp.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Identification of a gonadotropin-releasing hormone-responsive region in the glycoprotein hormone alpha-subunit promoter. Transcriptional regulation of the glycoprotein hormone alpha-subunit gene has been studied extensively in placental cells, but much less is known about its regulation in the pituitary gland. In this study, transcriptional control of the human alpha-subunit gene by GnRH was analyzed using transient expression assays in primary cultures of rat pituitary cells using alpha promoter constructs linked to a luciferase reporter gene. Deletion mutants between -846 and -156 basepairs (bp) had little effect on basal expression, but further deletion to -132 bp reduced basal activity by approximately 50%. Deletion of a cAMP response element between -132 and -99 bp caused a marked loss of basal activity, reducing expression to that of background luciferase activity. The same constructs were analyzed for cAMP responsiveness in primary pituitary cells. The degree of stimulation with 1 mM 8-bromo-cAMP (3.6- to 6.0-fold) was relatively unaffected by deletions from -846 to -132 bp, whereas cAMP stimulation was decreased by further deletion to -99 bp, consistent with the presence of previously defined cAMP response elements in this region of the alpha promoter. GnRH stimulation of alpha promoter activity was highly dependent upon the time of hormone addition after transfection, being most effective when added soon after transfection. Under optimal conditions, GnRH stimulated -846 alpha LUC expression by 20-fold. GnRH responsiveness was retained with deletion to -346 bp, but it was decreased by 55% after deletion to -280 bp and by 79% with deletion to -244 bp.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282669", "title": "Posttranscriptional regulation of albumin and alpha-fetoprotein messenger RNA by transforming growth factor-beta 1 requires de novo RNA and protein synthesis.", "content": "Transforming growth factor-beta (TGF beta) has been implicated in the regulation of hepatocyte function. We have examined TGF beta 1 regulation of albumin and alpha-fetoprotein (AFP) mRNA levels in a well differentiated mouse hepatoma cell line (BWTG3). TGF beta 1 reversibly decreased steady state mRNA levels of both albumin and AFP. By nuclear run-on assays, we found that TGF beta 1 caused no significant change in transcription rates for albumin or AFP. Pretreatment with actinomycin-D prevented the TGF beta 1-induced decrease in albumin and AFP mRNA levels. Also, if cells were treated with actinomycin-D after a 12-h exposure to TGF beta 1, actinomycin-D abrogated the further decrease in albumin and AFP mRNA levels that occurred after treatment with TGF beta 1 alone. Cycloheximide pretreatment blocked the TGF beta 1-induced decrease in albumin and AFP mRNA levels. TGF beta 1 altered neither the rate of BWTG3 cell growth nor the levels of mRNA for the growth-associated protooncogene c-myc. These data suggest that TGF beta 1 has regulatory effects on specific hepatocyte functions that are independent of growth regulatory effects. The decrease in albumin and AFP mRNAs caused by TGF beta 1 is posttranscriptional and dependent upon de novo RNA and protein synthesis.", "contents": "Posttranscriptional regulation of albumin and alpha-fetoprotein messenger RNA by transforming growth factor-beta 1 requires de novo RNA and protein synthesis. Transforming growth factor-beta (TGF beta) has been implicated in the regulation of hepatocyte function. We have examined TGF beta 1 regulation of albumin and alpha-fetoprotein (AFP) mRNA levels in a well differentiated mouse hepatoma cell line (BWTG3). TGF beta 1 reversibly decreased steady state mRNA levels of both albumin and AFP. By nuclear run-on assays, we found that TGF beta 1 caused no significant change in transcription rates for albumin or AFP. Pretreatment with actinomycin-D prevented the TGF beta 1-induced decrease in albumin and AFP mRNA levels. Also, if cells were treated with actinomycin-D after a 12-h exposure to TGF beta 1, actinomycin-D abrogated the further decrease in albumin and AFP mRNA levels that occurred after treatment with TGF beta 1 alone. Cycloheximide pretreatment blocked the TGF beta 1-induced decrease in albumin and AFP mRNA levels. TGF beta 1 altered neither the rate of BWTG3 cell growth nor the levels of mRNA for the growth-associated protooncogene c-myc. These data suggest that TGF beta 1 has regulatory effects on specific hepatocyte functions that are independent of growth regulatory effects. The decrease in albumin and AFP mRNAs caused by TGF beta 1 is posttranscriptional and dependent upon de novo RNA and protein synthesis."} {"id": "PMID:1282670", "title": "Endothelial cells express insulin-like growth factor-binding proteins 2 to 6.", "content": "Cultured endothelial cells have been shown to produce insulin-like growth factor-binding proteins (IGFBPs); however, the identity of these BPs has not been defined. We now demonstrate that cultured bovine endothelial cells produce IGFBP2, IGFBP3, and IGFBP4 and have mRNA specific for IGFBP2, -3, -4, -5 and -6. DNA probes for bovine IGFBP2-6 were obtained by polymerase chain reaction (PCR) amplification of cDNA from bovine large vessel pulmonary artery and aortic endothelial cells as well as omental and periaortic fat microvessel cells, using oligonucleotide primers whose sequences were based on the reported cDNA sequences of IGFBP2-6. The PCR-derived probes were labeled with 32P and used for Northern blot analysis of RNAs obtained from the four bovine endothelial cell types. Transcripts corresponding to IGFBP2-6 were found in RNA from large vessel endothelial cells (bovine pulmonary artery and bovine aorta) and microvessel cells (periaortic and omental fat). The PCR-derived probe for IGFBP4 was used to screen a bovine pulmonary artery cDNA library for a full-length bovine IGFBP4 cDNA clone. One positive clone, containing a single EcoRI insert of approximately 2.0 kilobases, was selected for further characterization by DNA sequence analysis. This clone contained an open reading frame encoding a 258-amino acid protein that was 97% identical to human IGFBP4, 268 basepairs of 5'-untranslated region, and a longer 1044 basepairs of 3'-untranslated region. IGFBP4 protein was purified from bovine pulmonary artery-conditioned medium, shown to have N-terminal amino acid sequence DEAIHCPPCSEEKLARCR (identical to human IGFBP4) and to be secreted in glycosylated and nonglycosylated forms. Immunoblots further demonstrated that microvessel cells, at early passage, secrete predominantly IGFBP2 and IGFBP3, while large vessel cells, at early and late passages, secrete IGFBP3 and IGFBP4. Thus, cultured bovine endothelial cells synthesize and secrete IGFBP2, IGFBP3, and IGFBP4 and have mRNA encoding IGFBP2-6. The production of specific IGFBPs by endothelial cells raises the interesting possibility that the vascular endothelium contributes to circulating and tissue levels of specific IGFBPs in vivo.", "contents": "Endothelial cells express insulin-like growth factor-binding proteins 2 to 6. Cultured endothelial cells have been shown to produce insulin-like growth factor-binding proteins (IGFBPs); however, the identity of these BPs has not been defined. We now demonstrate that cultured bovine endothelial cells produce IGFBP2, IGFBP3, and IGFBP4 and have mRNA specific for IGFBP2, -3, -4, -5 and -6. DNA probes for bovine IGFBP2-6 were obtained by polymerase chain reaction (PCR) amplification of cDNA from bovine large vessel pulmonary artery and aortic endothelial cells as well as omental and periaortic fat microvessel cells, using oligonucleotide primers whose sequences were based on the reported cDNA sequences of IGFBP2-6. The PCR-derived probes were labeled with 32P and used for Northern blot analysis of RNAs obtained from the four bovine endothelial cell types. Transcripts corresponding to IGFBP2-6 were found in RNA from large vessel endothelial cells (bovine pulmonary artery and bovine aorta) and microvessel cells (periaortic and omental fat). The PCR-derived probe for IGFBP4 was used to screen a bovine pulmonary artery cDNA library for a full-length bovine IGFBP4 cDNA clone. One positive clone, containing a single EcoRI insert of approximately 2.0 kilobases, was selected for further characterization by DNA sequence analysis. This clone contained an open reading frame encoding a 258-amino acid protein that was 97% identical to human IGFBP4, 268 basepairs of 5'-untranslated region, and a longer 1044 basepairs of 3'-untranslated region. IGFBP4 protein was purified from bovine pulmonary artery-conditioned medium, shown to have N-terminal amino acid sequence DEAIHCPPCSEEKLARCR (identical to human IGFBP4) and to be secreted in glycosylated and nonglycosylated forms. Immunoblots further demonstrated that microvessel cells, at early passage, secrete predominantly IGFBP2 and IGFBP3, while large vessel cells, at early and late passages, secrete IGFBP3 and IGFBP4. Thus, cultured bovine endothelial cells synthesize and secrete IGFBP2, IGFBP3, and IGFBP4 and have mRNA encoding IGFBP2-6. The production of specific IGFBPs by endothelial cells raises the interesting possibility that the vascular endothelium contributes to circulating and tissue levels of specific IGFBPs in vivo."} {"id": "PMID:1282671", "title": "Cholera toxin-sensitive 3',5'-cyclic adenosine monophosphate and calcium signals of the human dopamine-D1 receptor: selective potentiation by protein kinase A.", "content": "The signal transduction pathways of the dopamine-D1 receptor were investigated in two cell types stably transfected with the human D1 receptor cDNA, rat pituitary GH4C1 cells (GH4-hD1), and mouse Ltk-fibroblast cells (L-hD1). In both GH4-hD1 and L-hD1 cell lines, stimulation of the dopamine-D1 receptor induced a marked increase in cAMP accumulation. In addition, dopamine potentiated activation of L-type voltage-dependent calcium channels in a cAMP-dependent manner in GH4-hD1 cells. However, in L-hD1 cells, dopamine increased cytosolic free calcium concentrations ([Ca++]i) by mobilization of intracellular calcium rather than by calcium influx. This effect was correlated with a dopamine-induced enhancement of phospholipase C activity in L-hD1 cells. Pretreatment (24 h) with cholera toxin (CTX) was used to maximally activate the GTP-binding protein (G protein) Gs, causing a maximal elevation of cAMP levels and uncoupling the D1 receptor from Gs. The described actions of dopamine in both cell lines were abolished by pretreatment with CTX, indicating that CTX substrates (e.g. Gs) may mediate these actions. The blockade by CTX was not due to CTX-induced elevation of cAMP, since pretreatment with forskolin or 8-bromo-cAMP to activate cAMP-dependent protein kinase did not inhibit dopamine actions nor alter basal [Ca++]i. Pretreatment (1-3 h) of L-hD1 cells with forskolin (10 microM) or 8-bromo-cAMP (5 mM) altered neither the basal activity of phospholipase C nor basal [Ca++]i in L-hD1 cells but greatly enhanced the dopamine-induced increase of phosphatidyl inositol turnover and [Ca++]i. From these results we conclude that: 1) the dopamine-D1 receptor induces multiple and cell-specific signals, including elevation of cAMP levels in both GH and L cells, cAMP-dependent activation and potentiation of opening of L-type voltage-dependent calcium channel in GH cells, and a novel phosphatidyl inositol-linked mobilization of cellular calcium in L cells; 2) coupling of the D1 receptor to these responses involves CTX-sensitive proteins, possibly Gs; and 3) acute preactivation of cAMP-dependent protein kinase can markedly enhance, rather than attenuate, certain pathways of dopamine-D1 transmembrane signaling.", "contents": "Cholera toxin-sensitive 3',5'-cyclic adenosine monophosphate and calcium signals of the human dopamine-D1 receptor: selective potentiation by protein kinase A. The signal transduction pathways of the dopamine-D1 receptor were investigated in two cell types stably transfected with the human D1 receptor cDNA, rat pituitary GH4C1 cells (GH4-hD1), and mouse Ltk-fibroblast cells (L-hD1). In both GH4-hD1 and L-hD1 cell lines, stimulation of the dopamine-D1 receptor induced a marked increase in cAMP accumulation. In addition, dopamine potentiated activation of L-type voltage-dependent calcium channels in a cAMP-dependent manner in GH4-hD1 cells. However, in L-hD1 cells, dopamine increased cytosolic free calcium concentrations ([Ca++]i) by mobilization of intracellular calcium rather than by calcium influx. This effect was correlated with a dopamine-induced enhancement of phospholipase C activity in L-hD1 cells. Pretreatment (24 h) with cholera toxin (CTX) was used to maximally activate the GTP-binding protein (G protein) Gs, causing a maximal elevation of cAMP levels and uncoupling the D1 receptor from Gs. The described actions of dopamine in both cell lines were abolished by pretreatment with CTX, indicating that CTX substrates (e.g. Gs) may mediate these actions. The blockade by CTX was not due to CTX-induced elevation of cAMP, since pretreatment with forskolin or 8-bromo-cAMP to activate cAMP-dependent protein kinase did not inhibit dopamine actions nor alter basal [Ca++]i. Pretreatment (1-3 h) of L-hD1 cells with forskolin (10 microM) or 8-bromo-cAMP (5 mM) altered neither the basal activity of phospholipase C nor basal [Ca++]i in L-hD1 cells but greatly enhanced the dopamine-induced increase of phosphatidyl inositol turnover and [Ca++]i. From these results we conclude that: 1) the dopamine-D1 receptor induces multiple and cell-specific signals, including elevation of cAMP levels in both GH and L cells, cAMP-dependent activation and potentiation of opening of L-type voltage-dependent calcium channel in GH cells, and a novel phosphatidyl inositol-linked mobilization of cellular calcium in L cells; 2) coupling of the D1 receptor to these responses involves CTX-sensitive proteins, possibly Gs; and 3) acute preactivation of cAMP-dependent protein kinase can markedly enhance, rather than attenuate, certain pathways of dopamine-D1 transmembrane signaling."} {"id": "PMID:1282672", "title": "Beta 1 isoform-specific regulation of a triiodothyronine-induced gene during cerebellar development.", "content": "Although tissue-specific expression of the alpha 1 and beta 1 thyroid hormone receptors (TR-alpha 1 and TR-beta 1) suggests isoform-specific function, transfection studies to date have failed to show consistent differences in their ability to regulate gene expression. We here provide evidence that TR-beta 1 but not TR-alpha 1 regulates the expression of the gene coding for PCP-2 in cerebellar Purkinje cells during neonatal rat development and that such regulation appears to be both T3 dependent and T3 independent. Examination of neonatal rats revealed that the levels of three mRNAs expressed in cerebellar Purkinje cells (myoinositol-1,4,5-triphosphate receptor, calbindin, and PCP-2) rise from neonatal day 1 to day 15. This rise is preceded by the previously documented surge in brain T3 and TR-beta 1. Methimazole-induced hypothyroidism sharply reduces, but does not abolish, the rise in these mRNAs. Concomitant T3 administration normalizes the process. In order to establish more directly the role of TR-beta 1 and T3, cotransfection experiments were performed in CHO cells with PCP-2-lacZ construct and TR isoforms. These studies showed that TR-beta 1, even in the absence of T3, regulated the expression of the transfected PCP-2 construct. T3 augments the response to TR-beta 1 alone by 40% (P < .01). TR-alpha 1 had no effect on PCP-2-lacZ expression either in the presence or absence of T3.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Beta 1 isoform-specific regulation of a triiodothyronine-induced gene during cerebellar development. Although tissue-specific expression of the alpha 1 and beta 1 thyroid hormone receptors (TR-alpha 1 and TR-beta 1) suggests isoform-specific function, transfection studies to date have failed to show consistent differences in their ability to regulate gene expression. We here provide evidence that TR-beta 1 but not TR-alpha 1 regulates the expression of the gene coding for PCP-2 in cerebellar Purkinje cells during neonatal rat development and that such regulation appears to be both T3 dependent and T3 independent. Examination of neonatal rats revealed that the levels of three mRNAs expressed in cerebellar Purkinje cells (myoinositol-1,4,5-triphosphate receptor, calbindin, and PCP-2) rise from neonatal day 1 to day 15. This rise is preceded by the previously documented surge in brain T3 and TR-beta 1. Methimazole-induced hypothyroidism sharply reduces, but does not abolish, the rise in these mRNAs. Concomitant T3 administration normalizes the process. In order to establish more directly the role of TR-beta 1 and T3, cotransfection experiments were performed in CHO cells with PCP-2-lacZ construct and TR isoforms. These studies showed that TR-beta 1, even in the absence of T3, regulated the expression of the transfected PCP-2 construct. T3 augments the response to TR-beta 1 alone by 40% (P < .01). TR-alpha 1 had no effect on PCP-2-lacZ expression either in the presence or absence of T3.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282673", "title": "Effect of growth hormone on levels of differentially processed insulin-like growth factor I mRNAs in total and polysomal mRNA populations.", "content": "As a result of multiple transcription initiation sites and differential splicing involving the first exons and alternate exon use, many insulin-like growth factor I (IGF-I) mRNA species are produced. In the present study, we have assessed the effect of GH on transcription start site usage and splicing and have determined the apparent in vivo translatability of IGF-I mRNAs with different 5'-untranslated region (UTR) sequences by comparing their abundance in total and polysomal RNA fractions from control, hypophysectomized, and GH-treated hypophysectomized rats. Hypophysectomy decreased the level of all IGF-I mRNA species, but those initiated at start site 3 in exon 1 and the major start site in exon 2 were preferentially reduced. These same variants were preferentially increased by GH treatment. Under all conditions, exon 1 mRNAs with shorter 5'-UTR sequences were enriched in polysomal RNA at the expense of IGF-I mRNAs with long 5'-UTR sequences, in accordance with the scanning model of translation initiation. Exon 2-derived mRNAs, on the other hand, which have short 5'-UTR sequences, were not enriched on polysomes, suggesting that some aspect of the exon 2-derived 5'-UTR other than length influences translation in vivo. These results demonstrate that transcription within exon 1 and between exons 1 and 2 is differentially regulated by GH status and that the variant IGF-I mRNA species resulting from the complex patterns of transcription initiation and splicing in these leader exons are differentially translated in vivo.", "contents": "Effect of growth hormone on levels of differentially processed insulin-like growth factor I mRNAs in total and polysomal mRNA populations. As a result of multiple transcription initiation sites and differential splicing involving the first exons and alternate exon use, many insulin-like growth factor I (IGF-I) mRNA species are produced. In the present study, we have assessed the effect of GH on transcription start site usage and splicing and have determined the apparent in vivo translatability of IGF-I mRNAs with different 5'-untranslated region (UTR) sequences by comparing their abundance in total and polysomal RNA fractions from control, hypophysectomized, and GH-treated hypophysectomized rats. Hypophysectomy decreased the level of all IGF-I mRNA species, but those initiated at start site 3 in exon 1 and the major start site in exon 2 were preferentially reduced. These same variants were preferentially increased by GH treatment. Under all conditions, exon 1 mRNAs with shorter 5'-UTR sequences were enriched in polysomal RNA at the expense of IGF-I mRNAs with long 5'-UTR sequences, in accordance with the scanning model of translation initiation. Exon 2-derived mRNAs, on the other hand, which have short 5'-UTR sequences, were not enriched on polysomes, suggesting that some aspect of the exon 2-derived 5'-UTR other than length influences translation in vivo. These results demonstrate that transcription within exon 1 and between exons 1 and 2 is differentially regulated by GH status and that the variant IGF-I mRNA species resulting from the complex patterns of transcription initiation and splicing in these leader exons are differentially translated in vivo."} {"id": "PMID:1282674", "title": "Role of nitric oxide in antagonistic effects of transforming growth factor-beta and interleukin-1 beta on the beating rate of cultured cardiac myocytes.", "content": "We have recently shown that transforming growth factor-beta (TGF beta) acts in an autocrine manner to maintain the beating rate of neonatal rat cardiac myocytes cultured in serum-free medium on cardiac fibroblast matrix. Interleukin-1 beta (IL-1 beta) suppresses the myocyte-beating rate, and TGF beta antagonizes this effect. We now show that TGF beta and IL-1 beta also have antagonistic effects on the secretion of nitric oxide (NO) by these myocytes, and that NO secretion, the activity of NO synthase (NOS), and expression of the inducible form of NOS correlate inversely with the effects of these two agents on the beating rate. Western blot analysis shows that treatment of myocytes with TGF beta antagonizes the induction of NOS after treatment with IL-1 beta. Release of NO, induced by IL-1 beta, is dependent upon the availability of the substrate, L-arginine, and is suppressed by a competitive inhibitor, NG-monomethyl-L-arginine. L-Arginine (> 0.25 mM) also suppresses, and NG-monomethyl-L-arginine (> 0.5 mM) enhances the myocyte-beating rate. Treatment with IL-1 beta, but not TGF beta, increases cellular cGMP, presumably by activation of guanylate cyclase by NO. Methylene blue, an inhibitor of guanylate cyclase, reverses the suppression of beating caused by IL-1 beta. Bacterial lipopolysaccharide, present in the serum-free medium, is a coinducer of NO secretion. The suppressive effects of NO on the beating rate can be overcome by altering either the set of cytokines employed to induce NO or the matrix on which the myocytes are cultured, demonstrating that additional parameters are also involved in regulation of the beating rate.", "contents": "Role of nitric oxide in antagonistic effects of transforming growth factor-beta and interleukin-1 beta on the beating rate of cultured cardiac myocytes. We have recently shown that transforming growth factor-beta (TGF beta) acts in an autocrine manner to maintain the beating rate of neonatal rat cardiac myocytes cultured in serum-free medium on cardiac fibroblast matrix. Interleukin-1 beta (IL-1 beta) suppresses the myocyte-beating rate, and TGF beta antagonizes this effect. We now show that TGF beta and IL-1 beta also have antagonistic effects on the secretion of nitric oxide (NO) by these myocytes, and that NO secretion, the activity of NO synthase (NOS), and expression of the inducible form of NOS correlate inversely with the effects of these two agents on the beating rate. Western blot analysis shows that treatment of myocytes with TGF beta antagonizes the induction of NOS after treatment with IL-1 beta. Release of NO, induced by IL-1 beta, is dependent upon the availability of the substrate, L-arginine, and is suppressed by a competitive inhibitor, NG-monomethyl-L-arginine. L-Arginine (> 0.25 mM) also suppresses, and NG-monomethyl-L-arginine (> 0.5 mM) enhances the myocyte-beating rate. Treatment with IL-1 beta, but not TGF beta, increases cellular cGMP, presumably by activation of guanylate cyclase by NO. Methylene blue, an inhibitor of guanylate cyclase, reverses the suppression of beating caused by IL-1 beta. Bacterial lipopolysaccharide, present in the serum-free medium, is a coinducer of NO secretion. The suppressive effects of NO on the beating rate can be overcome by altering either the set of cytokines employed to induce NO or the matrix on which the myocytes are cultured, demonstrating that additional parameters are also involved in regulation of the beating rate."} {"id": "PMID:1282676", "title": "Growth inhibition of glioma cells by liposome-mediated cell transfection with tumor necrosis factor-alpha gene--its enhancement by prior gamma-interferon treatment.", "content": "A new approach to the treatment of malignant glioma is cytokine gene therapy to produce growth inhibitors in cells. Previously, we showed that human glioma cells selectively transfected with the gene of interferon (IFN)-beta and/or IFN-gamma by our novel liposomes tagged with monoclonal antibody against a glioma-associated antigen achieved a remarkable growth inhibition effect. In the present experiment, we demonstrated the effectiveness of gene therapy against glioma cells using liposomes bearing a plasmid containing the gene for tumor necrosis factor (TNF)-alpha. We also found that the effect of endogenous TNF-alpha was enhanced by treatment of IFN-gamma prior to the transfection with the TNF-alpha gene.", "contents": "Growth inhibition of glioma cells by liposome-mediated cell transfection with tumor necrosis factor-alpha gene--its enhancement by prior gamma-interferon treatment. A new approach to the treatment of malignant glioma is cytokine gene therapy to produce growth inhibitors in cells. Previously, we showed that human glioma cells selectively transfected with the gene of interferon (IFN)-beta and/or IFN-gamma by our novel liposomes tagged with monoclonal antibody against a glioma-associated antigen achieved a remarkable growth inhibition effect. In the present experiment, we demonstrated the effectiveness of gene therapy against glioma cells using liposomes bearing a plasmid containing the gene for tumor necrosis factor (TNF)-alpha. We also found that the effect of endogenous TNF-alpha was enhanced by treatment of IFN-gamma prior to the transfection with the TNF-alpha gene."} {"id": "PMID:1282677", "title": "Appearance of collagen fibers in the cerebral vascular wall following subarachnoid hemorrhage.", "content": "Ultrastructural examinations of the cerebral vascular wall following subarachnoid hemorrhage (SAH) demonstrated that collagen fibrils developed in the muscle layer near the adventitia in the early stage of SAH and increased in number and volume with time. These findings suggest that accelerating factors of collagen synthesis in the muscle layer may be released from the adventitial side, and collagen synthesis is induced by extravascular factors. The changes of collagen volume with time suggest collagen to be an important phenomenon of persistent vasospasm after SAH. Histoimmunological studies showed that increased collagen fibers in the tunica media were mainly type III collagen, implying that cerebral vasospasm may be related to chemical inflammation.", "contents": "Appearance of collagen fibers in the cerebral vascular wall following subarachnoid hemorrhage. Ultrastructural examinations of the cerebral vascular wall following subarachnoid hemorrhage (SAH) demonstrated that collagen fibrils developed in the muscle layer near the adventitia in the early stage of SAH and increased in number and volume with time. These findings suggest that accelerating factors of collagen synthesis in the muscle layer may be released from the adventitial side, and collagen synthesis is induced by extravascular factors. The changes of collagen volume with time suggest collagen to be an important phenomenon of persistent vasospasm after SAH. Histoimmunological studies showed that increased collagen fibers in the tunica media were mainly type III collagen, implying that cerebral vasospasm may be related to chemical inflammation."} {"id": "PMID:1282678", "title": "Worldwide distribution of moyamoya disease.", "content": "Many cases of spontaneous occlusion of the circle of Willis (moyamoya disease) have been reported in Japan, but the worldwide distribution is unclear. The total number of cases in each country reported in the literature and complications were evaluated. A total of 1063 cases have occurred worldwide excluding Japan. Cases were observed most frequently in Asia and in people of non-Caucasian origin.", "contents": "Worldwide distribution of moyamoya disease. Many cases of spontaneous occlusion of the circle of Willis (moyamoya disease) have been reported in Japan, but the worldwide distribution is unclear. The total number of cases in each country reported in the literature and complications were evaluated. A total of 1063 cases have occurred worldwide excluding Japan. Cases were observed most frequently in Asia and in people of non-Caucasian origin."} {"id": "PMID:1282679", "title": "Nontraumatic intradiploic arachnoid cysts--report of five cases.", "content": "Five cases of nontraumatic intradiploic arachnoid cysts in elderly patients are reported. All cysts were located in the occipital bone and appeared as well-demarcated radiolucent lesions. The cysts were multiple in three cases. Presenting symptoms included headache or dizziness, but most lesions were asymptomatic and found incidentally. In the most recent three cases, magnetic resonance (MR) imaging revealed intradiploic cysts containing cerebrospinal fluid (CSF) with cerebellar herniation. Operation found the cysts filled with CSF and dural defects through which cerebellar tissue was herniating. In two patients, CSF leakage from the outer table occurred. Intradiploic arachnoid cyst seems to be congenital in origin but commonly found in the elderly. MR imaging is the most useful diagnostic method for differential diagnosis from other osteolytic skull lesions.", "contents": "Nontraumatic intradiploic arachnoid cysts--report of five cases. Five cases of nontraumatic intradiploic arachnoid cysts in elderly patients are reported. All cysts were located in the occipital bone and appeared as well-demarcated radiolucent lesions. The cysts were multiple in three cases. Presenting symptoms included headache or dizziness, but most lesions were asymptomatic and found incidentally. In the most recent three cases, magnetic resonance (MR) imaging revealed intradiploic cysts containing cerebrospinal fluid (CSF) with cerebellar herniation. Operation found the cysts filled with CSF and dural defects through which cerebellar tissue was herniating. In two patients, CSF leakage from the outer table occurred. Intradiploic arachnoid cyst seems to be congenital in origin but commonly found in the elderly. MR imaging is the most useful diagnostic method for differential diagnosis from other osteolytic skull lesions."} {"id": "PMID:1282680", "title": "Recurrent brain abscess associated with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease)--case report.", "content": "A 53-year-old mentally handicapped female with hereditary hemorrhagic telangiectasia complicated by pulmonary arteriovenous fistula developed a recurrent brain abscess in the left frontal region. She responded well to surgical drainage and antibiotic therapy. Previously, she had two brain abscesses of the left parieto-occipital and right parietal regions removed on separate occasions at 38 and 40 years of age. Although pulmonary arteriovenous fistula was eventually confirmed by angiography at age 41 years, surgical removal of the pulmonary lesion was not indicated due to multiplicity and large vascular shunting. Early recognition of pulmonary arteriovenous fistula in patients with hereditary hemorrhagic telangiectasia is emphasized for diagnosis of brain abscess and prevention of recurrence.", "contents": "Recurrent brain abscess associated with hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease)--case report. A 53-year-old mentally handicapped female with hereditary hemorrhagic telangiectasia complicated by pulmonary arteriovenous fistula developed a recurrent brain abscess in the left frontal region. She responded well to surgical drainage and antibiotic therapy. Previously, she had two brain abscesses of the left parieto-occipital and right parietal regions removed on separate occasions at 38 and 40 years of age. Although pulmonary arteriovenous fistula was eventually confirmed by angiography at age 41 years, surgical removal of the pulmonary lesion was not indicated due to multiplicity and large vascular shunting. Early recognition of pulmonary arteriovenous fistula in patients with hereditary hemorrhagic telangiectasia is emphasized for diagnosis of brain abscess and prevention of recurrence."} {"id": "PMID:1282681", "title": "Traumatic internal carotid artery occlusion--case report.", "content": "A 20-year-old male was admitted comatose immediately after a motorcycle accident. Initial computed tomography demonstrated traumatic subarachnoid hemorrhage, and the diagnosis of traumatic internal carotid artery occlusion was established by angiography. Conservative management improved his symptoms, but eventually he died from delayed traumatic apoplexy. Traumatic internal carotid artery occlusion is relatively rare, but is serious and requires early diagnosis and treatment. For patients with severe head trauma and vascular occlusion, anticoagulants are contraindicated, and frequent follow-up angiography is recommended.", "contents": "Traumatic internal carotid artery occlusion--case report. A 20-year-old male was admitted comatose immediately after a motorcycle accident. Initial computed tomography demonstrated traumatic subarachnoid hemorrhage, and the diagnosis of traumatic internal carotid artery occlusion was established by angiography. Conservative management improved his symptoms, but eventually he died from delayed traumatic apoplexy. Traumatic internal carotid artery occlusion is relatively rare, but is serious and requires early diagnosis and treatment. For patients with severe head trauma and vascular occlusion, anticoagulants are contraindicated, and frequent follow-up angiography is recommended."} {"id": "PMID:1282682", "title": "Moyamoya disease progressing from unilateral to bilateral involvement--case report.", "content": "A 2-year-old boy with unilateral moyamoya disease demonstrated progression to the bilateral condition 1 year later. Previous reports of progression from unilateral to bilateral moyamoya disease showed that all patients were children or relatively young, and developed ischemic symptoms as the initial manifestation. These findings suggest that a considerable proportion of unilateral pediatric cases are in the initial stage of moyamoya disease and will progress to the contralateral side in the future.", "contents": "Moyamoya disease progressing from unilateral to bilateral involvement--case report. A 2-year-old boy with unilateral moyamoya disease demonstrated progression to the bilateral condition 1 year later. Previous reports of progression from unilateral to bilateral moyamoya disease showed that all patients were children or relatively young, and developed ischemic symptoms as the initial manifestation. These findings suggest that a considerable proportion of unilateral pediatric cases are in the initial stage of moyamoya disease and will progress to the contralateral side in the future."} {"id": "PMID:1282683", "title": "Intracranial mycotic aneurysm caused by Aspergillus--case report.", "content": "A 75-year-old female with chronic renal failure diagnosed as Wegener's granulomatosis was receiving steroids and immunosuppressive agents when subarachnoid hemorrhage developed. Cerebral angiography showed a fusiform aneurysm arising from an angular branch of the left middle cerebral artery. Hemorrhage occurred and the aneurysm was excised by emergency surgery. Microscopic examination of the aneurysm revealed dense infiltration of hyphae identified as Aspergillus. She died of subsequent hemorrhage. Autopsy showed numerous Aspergillus hyphae in the lung. Fungal mycotic aneurysm should be considered in the differential diagnosis of an immunocompromised patient with subarachnoid hemorrhage.", "contents": "Intracranial mycotic aneurysm caused by Aspergillus--case report. A 75-year-old female with chronic renal failure diagnosed as Wegener's granulomatosis was receiving steroids and immunosuppressive agents when subarachnoid hemorrhage developed. Cerebral angiography showed a fusiform aneurysm arising from an angular branch of the left middle cerebral artery. Hemorrhage occurred and the aneurysm was excised by emergency surgery. Microscopic examination of the aneurysm revealed dense infiltration of hyphae identified as Aspergillus. She died of subsequent hemorrhage. Autopsy showed numerous Aspergillus hyphae in the lung. Fungal mycotic aneurysm should be considered in the differential diagnosis of an immunocompromised patient with subarachnoid hemorrhage."} {"id": "PMID:1282684", "title": "Skull base metastasis from gastric cancer--case report.", "content": "A 48-year-old male presented with a metastatic skull base tumor located on the right of the clivus and the sphenoid sinus, which originated from adenocarcinoma of the stomach. The initial symptom was abducens nerve paralysis and there were no symptoms of upper gastrointestinal tract throughout the course. This gastric cancer, which rarely metastasizes to the central nervous system or osseous system, caused multiple bone metastases which produced the neurological symptoms.", "contents": "Skull base metastasis from gastric cancer--case report. A 48-year-old male presented with a metastatic skull base tumor located on the right of the clivus and the sphenoid sinus, which originated from adenocarcinoma of the stomach. The initial symptom was abducens nerve paralysis and there were no symptoms of upper gastrointestinal tract throughout the course. This gastric cancer, which rarely metastasizes to the central nervous system or osseous system, caused multiple bone metastases which produced the neurological symptoms."} {"id": "PMID:1282685", "title": "Anaplastic astrocytoma of an oncocytic type occurring in the cerebellar vermis in Pierre Robin syndrome--case report.", "content": "A 44-year-old male with Pierre Robin syndrome and funnel chest was diagnosed with a tumor of the cerebellar vermis and spontaneous pneumothorax. He received tube thoracostomy for pneumothorax and ventriculoperitoneal shunt for hydrocephalus, followed by radiological examination, subtotal removal of the tumor, pneumonorrhaphy, and chemoradiotherapy. Light microscopy of the tumor sample revealed marked pleomorphism of the tumor cells and numerous giant cells, without mitotic figures. Microcystic changes due to vasogenic edema were also evident throughout the tumor. Electron microscopy showed more than 50% of all tumor cells to be oncocytes, with numerous mitochondria in the cytoplasm. The tumor was diagnosed as anaplastic astrocytoma of an oncocytic type.", "contents": "Anaplastic astrocytoma of an oncocytic type occurring in the cerebellar vermis in Pierre Robin syndrome--case report. A 44-year-old male with Pierre Robin syndrome and funnel chest was diagnosed with a tumor of the cerebellar vermis and spontaneous pneumothorax. He received tube thoracostomy for pneumothorax and ventriculoperitoneal shunt for hydrocephalus, followed by radiological examination, subtotal removal of the tumor, pneumonorrhaphy, and chemoradiotherapy. Light microscopy of the tumor sample revealed marked pleomorphism of the tumor cells and numerous giant cells, without mitotic figures. Microcystic changes due to vasogenic edema were also evident throughout the tumor. Electron microscopy showed more than 50% of all tumor cells to be oncocytes, with numerous mitochondria in the cytoplasm. The tumor was diagnosed as anaplastic astrocytoma of an oncocytic type."} {"id": "PMID:1282686", "title": "Innervation of the feline eyelids.", "content": "The innervation of the eyelids is incompletely understood. This is a particular problem for those who wish to develop animal models of eyelid dysfunction in humans. Blepharospasm, for example, is a disease of uncontrolled eyelid spasm that is difficult to manage clinically because the aetiology is not understood. The anatomical literature on eyelid innervation is sparse and even conflicting. We attempted to study eyelid innervation, both sensory and motor, with injection of horseradish peroxidase (HRP) into the superior eyelid, inferior eyelid, and bulbar conjunctiva. We used 13 anesthetized weanling cats. Shape and structure of the facial nucleus varied along its rostrocaudal extent, but there was a clear demarcation of lateral and medial division. HRP-filled facial nucleus cells were ipsilateral to the injection site, and label appeared throughout the rostrocaudal length. All injection sites, including bulbar conjunctiva, labelled facial nucleus neurons located with overlapping distribution, predominantly in the dorsal part of the lateral division. Likewise, heavy labelling occurred throughout the entire ipsilateral cranial cervical ganglion and the trigeminal ganglion in all kittens. Injection of upper or lower eyelids caused some labelling in the second through the fourth cervical spinal ganglia.", "contents": "Innervation of the feline eyelids. The innervation of the eyelids is incompletely understood. This is a particular problem for those who wish to develop animal models of eyelid dysfunction in humans. Blepharospasm, for example, is a disease of uncontrolled eyelid spasm that is difficult to manage clinically because the aetiology is not understood. The anatomical literature on eyelid innervation is sparse and even conflicting. We attempted to study eyelid innervation, both sensory and motor, with injection of horseradish peroxidase (HRP) into the superior eyelid, inferior eyelid, and bulbar conjunctiva. We used 13 anesthetized weanling cats. Shape and structure of the facial nucleus varied along its rostrocaudal extent, but there was a clear demarcation of lateral and medial division. HRP-filled facial nucleus cells were ipsilateral to the injection site, and label appeared throughout the rostrocaudal length. All injection sites, including bulbar conjunctiva, labelled facial nucleus neurons located with overlapping distribution, predominantly in the dorsal part of the lateral division. Likewise, heavy labelling occurred throughout the entire ipsilateral cranial cervical ganglion and the trigeminal ganglion in all kittens. Injection of upper or lower eyelids caused some labelling in the second through the fourth cervical spinal ganglia."} {"id": "PMID:1282687", "title": "Isolation of complementary DNAs for heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 genes and the expressions in post-ischaemic gerbil brain.", "content": "A complementary DNA (cDNA) library was constructed with a plasmid vector from cerebral cortices of gerbils at 8 h of reperfusion after 10 min of bilateral common carotid ligation. After the 3rd screening of this cDNA library with a human genomic DNA probe for HSP70 (pH2.3), 4 cDNA clones were isolated (named pGA3' pGB1' pGD3 and pGE4' respectively). Southern and Northern blot analysis, and partial nucleotide sequence analysis indicated that pGA3 and pGE4 were the HSP70 cDNA clones, and that pGB1 and pGD3 were the HSC70 cDNA clones, which selectively recognized HSP70 or HSC70 mRNA, respectively. HSP70 mRNA is present in a very small amount in normal controls, and is greatly induced after the transient ischaemia. HSC70 mRNA is constitutively expressed in a normal gerbil brain, but is still inducible. In situ hybridization study demonstrated that the HSP70 mRNA was present in a very small amount in the hippocampal pyramidal and dentate granule cells in the sham control, and that the mRNA was greatly induced in the cells of hippocampus, dentate gyrus, medial habenula, ventral thalamic nuclei, caudate putamen, ventromedial and arcuate hypothalamic nuclei, amygdaloid nuclei and cerebral cortex after 8 h of reperfusion. HSC70 mRNA was present in almost the same areas of sham control, and was slightly induced after 8 h of reperfusion. Our results indicate that HSP70 and HSC70 cDNA clones were first isolated from post-ischaemic gerbil brain, and selectively recognize HSP70 or HSC70 mRNA, respectively. A regional difference in the induction of the HSP70 and HSC70 mRNA in post-ischaemic gerbil brain was observed by in situ hybridization.", "contents": "Isolation of complementary DNAs for heat shock protein (HSP) 70 and heat shock cognate protein (HSC) 70 genes and the expressions in post-ischaemic gerbil brain. A complementary DNA (cDNA) library was constructed with a plasmid vector from cerebral cortices of gerbils at 8 h of reperfusion after 10 min of bilateral common carotid ligation. After the 3rd screening of this cDNA library with a human genomic DNA probe for HSP70 (pH2.3), 4 cDNA clones were isolated (named pGA3' pGB1' pGD3 and pGE4' respectively). Southern and Northern blot analysis, and partial nucleotide sequence analysis indicated that pGA3 and pGE4 were the HSP70 cDNA clones, and that pGB1 and pGD3 were the HSC70 cDNA clones, which selectively recognized HSP70 or HSC70 mRNA, respectively. HSP70 mRNA is present in a very small amount in normal controls, and is greatly induced after the transient ischaemia. HSC70 mRNA is constitutively expressed in a normal gerbil brain, but is still inducible. In situ hybridization study demonstrated that the HSP70 mRNA was present in a very small amount in the hippocampal pyramidal and dentate granule cells in the sham control, and that the mRNA was greatly induced in the cells of hippocampus, dentate gyrus, medial habenula, ventral thalamic nuclei, caudate putamen, ventromedial and arcuate hypothalamic nuclei, amygdaloid nuclei and cerebral cortex after 8 h of reperfusion. HSC70 mRNA was present in almost the same areas of sham control, and was slightly induced after 8 h of reperfusion. Our results indicate that HSP70 and HSC70 cDNA clones were first isolated from post-ischaemic gerbil brain, and selectively recognize HSP70 or HSC70 mRNA, respectively. A regional difference in the induction of the HSP70 and HSC70 mRNA in post-ischaemic gerbil brain was observed by in situ hybridization."} {"id": "PMID:1282688", "title": "Increased opening of blood-tumour barrier by leukotriene C4 is dependent on size of molecules.", "content": "Intracarotid injections of leukotriene C4 (LTC4) will increase blood-tumour barrier (BTB) permeability for 14C aminoisobutyric acid (AIB) in RG-2 tumours in rats. In this study, rats with RG-2 tumours were given 15 minute intracarotid infusions of LTC4 (5 micrograms total dose). Blood-tumour and BBB permeability were determined by quantitative autoradiography using different sized 14C tracers; AIB (103.1 daltons, radius = 2.8 A), Sucrose (342 daltons, radius = 5 A), Inulin (5000 daltons, radius = 15 A) and Dextran (70,000 daltons, radius = 60 A), respectively (n = 7 in each group). Permeability (Ki) within tumours for AIB, Sucrose and Inulin increased significantly after LTC4 infusion (92.7 +/- 15.0 vs 39.4 +/- 6.5, 47.8 +/- 5.2 vs 29.1 +/- 8.8, and 46.4 +/- 8.4 vs 26.4 +/- 4.8 microliters/gm/min, respectively, p < 0.01) (mean +/- SD). No significant change in Ki for 14C Dextran was observed. Increased permeability within tumours after LTC4 infusion is dependent on molecular size. This suggests that LTC4 opens tight junctions rather than increases vesicular transport through endothelial cells.", "contents": "Increased opening of blood-tumour barrier by leukotriene C4 is dependent on size of molecules. Intracarotid injections of leukotriene C4 (LTC4) will increase blood-tumour barrier (BTB) permeability for 14C aminoisobutyric acid (AIB) in RG-2 tumours in rats. In this study, rats with RG-2 tumours were given 15 minute intracarotid infusions of LTC4 (5 micrograms total dose). Blood-tumour and BBB permeability were determined by quantitative autoradiography using different sized 14C tracers; AIB (103.1 daltons, radius = 2.8 A), Sucrose (342 daltons, radius = 5 A), Inulin (5000 daltons, radius = 15 A) and Dextran (70,000 daltons, radius = 60 A), respectively (n = 7 in each group). Permeability (Ki) within tumours for AIB, Sucrose and Inulin increased significantly after LTC4 infusion (92.7 +/- 15.0 vs 39.4 +/- 6.5, 47.8 +/- 5.2 vs 29.1 +/- 8.8, and 46.4 +/- 8.4 vs 26.4 +/- 4.8 microliters/gm/min, respectively, p < 0.01) (mean +/- SD). No significant change in Ki for 14C Dextran was observed. Increased permeability within tumours after LTC4 infusion is dependent on molecular size. This suggests that LTC4 opens tight junctions rather than increases vesicular transport through endothelial cells."} {"id": "PMID:1282690", "title": "Polymerase chain reaction assay of mRNA using 28S rRNA as internal standard.", "content": "A method is developed for PCR assay of mRNA using 28S rRNA as internal standard and its applicability is reported for 4 types of mRNA. It consists of reverse transcription of total RNA using primers selective for 28S rRNA and the message of interest. Routinely the 28S reaction mix is diluted 20,000-fold and the dilution error is minimized by adding 10 microCi of 3H2O before the dilution and determining the level of 3H before and after the dilution. Aliquots from the diluted 28S mix and the undiluted reverse transcripts are co-amplified by PCR in the presence of 32P-dATP. The samples are analyzed by electrophoresis, bands detected by autoradiography and in each lane the ratio is determined between cpm in the band of interest and cpm in the 28S band. The ratio is a measure of the level of mRNA in the sample and can be used to monitor changes in mRNA during treatments, development and pathogenesis.", "contents": "Polymerase chain reaction assay of mRNA using 28S rRNA as internal standard. A method is developed for PCR assay of mRNA using 28S rRNA as internal standard and its applicability is reported for 4 types of mRNA. It consists of reverse transcription of total RNA using primers selective for 28S rRNA and the message of interest. Routinely the 28S reaction mix is diluted 20,000-fold and the dilution error is minimized by adding 10 microCi of 3H2O before the dilution and determining the level of 3H before and after the dilution. Aliquots from the diluted 28S mix and the undiluted reverse transcripts are co-amplified by PCR in the presence of 32P-dATP. The samples are analyzed by electrophoresis, bands detected by autoradiography and in each lane the ratio is determined between cpm in the band of interest and cpm in the 28S band. The ratio is a measure of the level of mRNA in the sample and can be used to monitor changes in mRNA during treatments, development and pathogenesis."} {"id": "PMID:1282691", "title": "Immunoblot detection of antibodies to myelin basic protein in Alzheimer's disease patients.", "content": "Based on a suspected pathological relationship of autoimmunity in Alzheimer's disease (AD), antibodies to myelin basic protein (MBP) were investigated in the sera of AD patients, healthy controls and disease controls. As detected by the protein-immunoblotting technique at a screening serum dilution of 1:400, sera from 16 of 18 (89%) AD patients were positive for antibodies to MBP. In contrast, sera from only 7 of 90 controls (healthy adults and elderlies, Parkinson's disease patients, mentally-retarded children and Down's syndrome patients) showed a positive reaction. This approximately 11-times higher incidence of antibodies to MBP in AD patients was statistically significant (P < or = 0.0001) and may indicate an autoimmune process in the pathophysiology of the disease.", "contents": "Immunoblot detection of antibodies to myelin basic protein in Alzheimer's disease patients. Based on a suspected pathological relationship of autoimmunity in Alzheimer's disease (AD), antibodies to myelin basic protein (MBP) were investigated in the sera of AD patients, healthy controls and disease controls. As detected by the protein-immunoblotting technique at a screening serum dilution of 1:400, sera from 16 of 18 (89%) AD patients were positive for antibodies to MBP. In contrast, sera from only 7 of 90 controls (healthy adults and elderlies, Parkinson's disease patients, mentally-retarded children and Down's syndrome patients) showed a positive reaction. This approximately 11-times higher incidence of antibodies to MBP in AD patients was statistically significant (P < or = 0.0001) and may indicate an autoimmune process in the pathophysiology of the disease."} {"id": "PMID:1282692", "title": "Origin and distribution of NADPH-diaphorase-positive neurons and fibers innervating the urinary bladder of the rat.", "content": "Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry was utilized to localize nitric oxide synthase (NOS), and thus sites where nitric oxide (NO) can be synthesized, within peripheral nervous system perikarya and fibers. Recent studies suggest that NO relaxes vascular and non-vascular smooth muscle. In this study, the origin and distribution of NADPH-diaphorase perikarya and fibers in the rat urinary bladder were examined. Results suggest that a small number of NADPH-diaphorase-positive perikarya are present within the bladder wall and within adjacent small ganglia. In addition, NADPH-diaphorase-positive nerve fibers were observed in the adventitial and muscular layers, subjacent to the urothelium and as perivascular fibers. After injection of the retrograde tracer fluorogold (FG) into the bladder wall, numerous FG-labeled perikarya in the major pelvic ganglia and the T13-L2, L6 and S1 dorsal root ganglia were NADPH-diaphorase positive. However, none of the FG-labeled perikarya in the inferior mesenteric ganglia were NADPH-diaphorase positive. The prevalence of NADPH-diaphorase-positive perikarya and fibers suggests that NO may serve a role in bladder function.", "contents": "Origin and distribution of NADPH-diaphorase-positive neurons and fibers innervating the urinary bladder of the rat. Nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase histochemistry was utilized to localize nitric oxide synthase (NOS), and thus sites where nitric oxide (NO) can be synthesized, within peripheral nervous system perikarya and fibers. Recent studies suggest that NO relaxes vascular and non-vascular smooth muscle. In this study, the origin and distribution of NADPH-diaphorase perikarya and fibers in the rat urinary bladder were examined. Results suggest that a small number of NADPH-diaphorase-positive perikarya are present within the bladder wall and within adjacent small ganglia. In addition, NADPH-diaphorase-positive nerve fibers were observed in the adventitial and muscular layers, subjacent to the urothelium and as perivascular fibers. After injection of the retrograde tracer fluorogold (FG) into the bladder wall, numerous FG-labeled perikarya in the major pelvic ganglia and the T13-L2, L6 and S1 dorsal root ganglia were NADPH-diaphorase positive. However, none of the FG-labeled perikarya in the inferior mesenteric ganglia were NADPH-diaphorase positive. The prevalence of NADPH-diaphorase-positive perikarya and fibers suggests that NO may serve a role in bladder function."} {"id": "PMID:1282693", "title": "Insect glial cells show differential expression of a glycolipid-derived, glucuronic acid-containing epitope throughout neurogenesis: detection during postembryogenesis and regeneration in the central nervous system of Tenebrio molitor L.", "content": "The monoclonal antibody CAF-1 recognises a glucuronic acid-containing epitope present on insect acidic glycolipids. Immunohistochemical analysis of the CAF-1 epitope has revealed its differential, temporal and spatial expression during postembryogenesis of the midbrain of Tenebrio molitor. Electron microscopic resolution demonstrated, that the CAF-1 epitope is expressed on glial cells that ensheath the glomeruli of the central body. Concomitantly, a differential pattern of expression was observed in the ventral nerve cord, exhibiting a serially homologous display on glial cells that ensheath neuronal somata in the cell body layer of the thoracic ganglia and ventral associative neuropil. Prominent, topologically restricted CAF-1 immunoreactivity was monitored in termination areas of sensory neurons in the ventral associative neuropil and corresponding nerves 6-48 h after extirpation of the respective sensory neuron somata. CAF-1 expression is correlated with structural reorganisation in postembryonic nervous tissue of T. molitor.", "contents": "Insect glial cells show differential expression of a glycolipid-derived, glucuronic acid-containing epitope throughout neurogenesis: detection during postembryogenesis and regeneration in the central nervous system of Tenebrio molitor L. The monoclonal antibody CAF-1 recognises a glucuronic acid-containing epitope present on insect acidic glycolipids. Immunohistochemical analysis of the CAF-1 epitope has revealed its differential, temporal and spatial expression during postembryogenesis of the midbrain of Tenebrio molitor. Electron microscopic resolution demonstrated, that the CAF-1 epitope is expressed on glial cells that ensheath the glomeruli of the central body. Concomitantly, a differential pattern of expression was observed in the ventral nerve cord, exhibiting a serially homologous display on glial cells that ensheath neuronal somata in the cell body layer of the thoracic ganglia and ventral associative neuropil. Prominent, topologically restricted CAF-1 immunoreactivity was monitored in termination areas of sensory neurons in the ventral associative neuropil and corresponding nerves 6-48 h after extirpation of the respective sensory neuron somata. CAF-1 expression is correlated with structural reorganisation in postembryonic nervous tissue of T. molitor."} {"id": "PMID:1282694", "title": "Nitric oxide synthase in rat brain is predominantly located at neuronal endoplasmic reticulum: an electron microscopic demonstration of NADPH-diaphorase activity.", "content": "Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) of the rat brain, apparently identical with nitric oxide (NO) synthase, was demonstrated at the electron microscopic level by means of the tetrazolium salt 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl)tetrazolium chloride (BSPT). BSPT is a non-osmiophilic compound that yields an insoluble, osmiophilic, and lipophobic formazan on reduction. The reaction product was deposited sharply on membranes of the endoplasmic reticulum including the nuclear envelope. Other membrane structures were, as a rule, free of reaction product, likewise mitochondria. Occasionally, however, the outer membrane of mitochondria was labeled, and their contents displayed a homogeneous, medium electron density. The findings suggest that NADPH-d, i.e. neuronal NO synthase, is a predominantly membrane-bound enzyme, which is ubiquitously distributed in cells of brain tissue, but highly concentrated in nerve cells described as 'NADPH-d-positive' at the light microscopic level.", "contents": "Nitric oxide synthase in rat brain is predominantly located at neuronal endoplasmic reticulum: an electron microscopic demonstration of NADPH-diaphorase activity. Nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) of the rat brain, apparently identical with nitric oxide (NO) synthase, was demonstrated at the electron microscopic level by means of the tetrazolium salt 2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl)tetrazolium chloride (BSPT). BSPT is a non-osmiophilic compound that yields an insoluble, osmiophilic, and lipophobic formazan on reduction. The reaction product was deposited sharply on membranes of the endoplasmic reticulum including the nuclear envelope. Other membrane structures were, as a rule, free of reaction product, likewise mitochondria. Occasionally, however, the outer membrane of mitochondria was labeled, and their contents displayed a homogeneous, medium electron density. The findings suggest that NADPH-d, i.e. neuronal NO synthase, is a predominantly membrane-bound enzyme, which is ubiquitously distributed in cells of brain tissue, but highly concentrated in nerve cells described as 'NADPH-d-positive' at the light microscopic level."} {"id": "PMID:1282695", "title": "cAMP-mediated second messenger mechanisms are involved in spinule formation in teleost cone horizontal cells.", "content": "A number of light adaptive changes of teleost horizontal cells are mediated by dopamine D1 receptors coupled positively with the cAMP second messenger system. Spinules, finger-like extensions from horizontal cell dendrites directed towards the cone pedicle cytoplasm, are formed in response to a stimulation of D1 receptors. We studied the second messenger mechanism associated with this process using isolated dark-adapted cyprinid retinae. Increasing intracellular cAMP concentrations by adding a membrane permeable analogue, or by stimulating the adenylate cyclase and simultaneously blocking the degradation of cAMP, resulted in a significant increase of spinule numbers in spite of the absence of light. In contradistinction to using isolated retinae for pharmacological experiments, injection of drugs into the vitreous had inconsistent or negative results.", "contents": "cAMP-mediated second messenger mechanisms are involved in spinule formation in teleost cone horizontal cells. A number of light adaptive changes of teleost horizontal cells are mediated by dopamine D1 receptors coupled positively with the cAMP second messenger system. Spinules, finger-like extensions from horizontal cell dendrites directed towards the cone pedicle cytoplasm, are formed in response to a stimulation of D1 receptors. We studied the second messenger mechanism associated with this process using isolated dark-adapted cyprinid retinae. Increasing intracellular cAMP concentrations by adding a membrane permeable analogue, or by stimulating the adenylate cyclase and simultaneously blocking the degradation of cAMP, resulted in a significant increase of spinule numbers in spite of the absence of light. In contradistinction to using isolated retinae for pharmacological experiments, injection of drugs into the vitreous had inconsistent or negative results."} {"id": "PMID:1282696", "title": "Phakomatous choristoma of the eyelid. Immunohistochemical and electron microscopic observations.", "content": "A 13-month-old Hispanic boy underwent excision of a congenital inferonasal orbital mass arising from the right lower lid. Results of histopathologic examination of the tumor showed a phakomatous choristoma of the eyelid. An immunohistochemical and electron microscopic study of this rare, benign, congenital tumor of lenticular anlage was performed. Immunohistochemistry was performed on 4-microns thick sections from paraffin-embedded tissue. Electron microscopy was performed on thin sections stained with uranyl acetate and lead citrate. The cuboidal epithelial cells that comprise this choristoma showed strongly positive cytoplasmic staining with S-100 protein and vimentin and focally positive staining with a keratin cocktail (AE1/AE3). Electron microscopy showed the presence of numerous 10-nm whorled cytoplasmic microfilaments within degenerating epithelial cells. The immunoreactivity of this tumor to keratin and vimentin are newly described in this detailed clinicopathologic report and, together with its S-100 positivity, support the proposal that this tumor is of lenticular anlage. The authors hypothesize that the intracytoplasmic 10-nm intermediate filaments observed with electron microscopic examination within the epithelial cells that comprise this choristoma represent vimentin as detected by immunohistochemistry.", "contents": "Phakomatous choristoma of the eyelid. Immunohistochemical and electron microscopic observations. A 13-month-old Hispanic boy underwent excision of a congenital inferonasal orbital mass arising from the right lower lid. Results of histopathologic examination of the tumor showed a phakomatous choristoma of the eyelid. An immunohistochemical and electron microscopic study of this rare, benign, congenital tumor of lenticular anlage was performed. Immunohistochemistry was performed on 4-microns thick sections from paraffin-embedded tissue. Electron microscopy was performed on thin sections stained with uranyl acetate and lead citrate. The cuboidal epithelial cells that comprise this choristoma showed strongly positive cytoplasmic staining with S-100 protein and vimentin and focally positive staining with a keratin cocktail (AE1/AE3). Electron microscopy showed the presence of numerous 10-nm whorled cytoplasmic microfilaments within degenerating epithelial cells. The immunoreactivity of this tumor to keratin and vimentin are newly described in this detailed clinicopathologic report and, together with its S-100 positivity, support the proposal that this tumor is of lenticular anlage. The authors hypothesize that the intracytoplasmic 10-nm intermediate filaments observed with electron microscopic examination within the epithelial cells that comprise this choristoma represent vimentin as detected by immunohistochemistry."} {"id": "PMID:1282699", "title": "Quantitative determination of morphometric indices of the total and perfused capillary network of the newborn pig brain.", "content": "The purpose of this study was to determine if the newborn pig brain had a reserve of unperfused capillaries during normoxia. To accomplish this, a method was developed to determine the volume fraction, surface area, and number of both total and perfused capillaries in the newborn pig brain. Newborn pigs of either sex, 2-7 d old, were used. FITC-dextran, molecular weight 147,000, was used as a plasma marker to visualize the perfused capillaries. Alkaline phosphatase staining was used to stain the total capillary bed of the brain. Our results showed that FITC-dextran stayed within the vascular compartment, as it was not seen in areas that were not subsequently visualized with alkaline phosphatase staining. Eighty-four to 86% of the alkaline phosphatase-stained capillaries could be visualized with perfusion markers (india ink or FITC-dextran) in different brain regions. Similar results were obtained in two animals using a basement membrane stain, silver methenamine. The total volume fraction of capillaries (mm3/mm3) was cortex 0.055 +/- 0.012, cerebellum 0.062 +/- 0.011, and medulla 0.039 +/- 0.012. Capillary surface area (mm2/mm3) of different brain regions averaged cortex 23.2 +/- 1.8, cerebellum 24.8 +/- 2.5, and medulla 15.8 +/- 2.9. The total number of capillaries (per mm2) was cortex 375 +/- 37, cerebellum 329 +/- 37, and medulla 216 +/- 32. The time course of filling of the capillaries indicated that approximately 50% were perfused at 6 s, which increased to over 80% at 12 s and remained unchanged thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Quantitative determination of morphometric indices of the total and perfused capillary network of the newborn pig brain. The purpose of this study was to determine if the newborn pig brain had a reserve of unperfused capillaries during normoxia. To accomplish this, a method was developed to determine the volume fraction, surface area, and number of both total and perfused capillaries in the newborn pig brain. Newborn pigs of either sex, 2-7 d old, were used. FITC-dextran, molecular weight 147,000, was used as a plasma marker to visualize the perfused capillaries. Alkaline phosphatase staining was used to stain the total capillary bed of the brain. Our results showed that FITC-dextran stayed within the vascular compartment, as it was not seen in areas that were not subsequently visualized with alkaline phosphatase staining. Eighty-four to 86% of the alkaline phosphatase-stained capillaries could be visualized with perfusion markers (india ink or FITC-dextran) in different brain regions. Similar results were obtained in two animals using a basement membrane stain, silver methenamine. The total volume fraction of capillaries (mm3/mm3) was cortex 0.055 +/- 0.012, cerebellum 0.062 +/- 0.011, and medulla 0.039 +/- 0.012. Capillary surface area (mm2/mm3) of different brain regions averaged cortex 23.2 +/- 1.8, cerebellum 24.8 +/- 2.5, and medulla 15.8 +/- 2.9. The total number of capillaries (per mm2) was cortex 375 +/- 37, cerebellum 329 +/- 37, and medulla 216 +/- 32. The time course of filling of the capillaries indicated that approximately 50% were perfused at 6 s, which increased to over 80% at 12 s and remained unchanged thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282697", "title": "[Influence of the inflammatory reaction on the distribution of alpha1-macroglobulin and pregnancy-associated alpha1-glycoprotein in the rat].", "content": "The authors studied the distribution of proteinase inhibitors in inflammation induced by intramuscular turpentine injection. It was found that it reduces the concentration of the studied proteins in the tissues, which is attended by an increase of their plasma levels. The store of pregnancy-associated alpha 1-glycoprotein in the tissues is rapidly depleted, while the concentration of alpha 1-microglobulin reduces to a relatively stable level. The role of the both proteins in the inflammatory process is discussed.", "contents": "[Influence of the inflammatory reaction on the distribution of alpha1-macroglobulin and pregnancy-associated alpha1-glycoprotein in the rat]. The authors studied the distribution of proteinase inhibitors in inflammation induced by intramuscular turpentine injection. It was found that it reduces the concentration of the studied proteins in the tissues, which is attended by an increase of their plasma levels. The store of pregnancy-associated alpha 1-glycoprotein in the tissues is rapidly depleted, while the concentration of alpha 1-microglobulin reduces to a relatively stable level. The role of the both proteins in the inflammatory process is discussed."} {"id": "PMID:1282698", "title": "[Content of trace elements and steroid hormones in blood and tissues of internal organs in experimental pulmonary fibrosis induced by intratracheal administration of bleomycetin].", "content": "Pulmonary fibrosis was produced in rats by intratracheal administration of bleomycetin. The development of the fibrous process in the lungs was attended by marked reduction of the zinc content in the tissues of the viscera, plasma, and formed elements of the blood, as well as of corticosterone and testosterone in blood plasma. Respiratory insufficiency is a probable cause of the developing zinc-deficiency which leads to disturbed synthesis of steroid hormones. Injection of exogenous testosterone normalizes partly the level of steroid hormones in the blood, improves the general condition of the animals, and facilitates an increase of body weight.", "contents": "[Content of trace elements and steroid hormones in blood and tissues of internal organs in experimental pulmonary fibrosis induced by intratracheal administration of bleomycetin]. Pulmonary fibrosis was produced in rats by intratracheal administration of bleomycetin. The development of the fibrous process in the lungs was attended by marked reduction of the zinc content in the tissues of the viscera, plasma, and formed elements of the blood, as well as of corticosterone and testosterone in blood plasma. Respiratory insufficiency is a probable cause of the developing zinc-deficiency which leads to disturbed synthesis of steroid hormones. Injection of exogenous testosterone normalizes partly the level of steroid hormones in the blood, improves the general condition of the animals, and facilitates an increase of body weight."} {"id": "PMID:1282700", "title": "In vivo study of phytanic acid alpha-oxidation in classic Refsum's disease and chondrodysplasia punctata.", "content": "A series of in vivo experiments is described in which [1-13C]phytanic acid was given as an oral substrate to a healthy subject and two patients showing an impairment in phytanic acid degradation, one with Refsum's disease and one with chondrodysplasia punctata. After intake of the substrate by the control in a dose of 20 mg/kg body weight, the production of 13CO2 was measured in exhaled breath air and the concomitant formation of labeled 2-hydroxyphytanic acid and of pristanic acid was demonstrated by plasma analysis. After application of a substrate dose of 1 mg/kg body weight to the control, no substantial amounts of 13CO2 were measured, whereas time-dependent analysis of labeled 2-hydroxyphytanic acid in plasma yielded a concentration curve superimposed upon the baseline value (0.2 mumol/L) of the unlabeled substance. Phytanic acid accumulated in plasma from the Refsum's disease patient [649 mumol/L, controls > 1 y (n = 100): < 10 mumol/L], whereas the pristanic acid concentration was within the control range [1.4 mumol/L, controls > 1 y (n = 100): < 3 mumol/L]. Low amounts of 2-hydroxyphytanic acid were found normally present [0.04 mumol/L, controls > 1 y (n = 11): < 0.2 mumol/L], and formation of labeled 2-hydroxyphytanic acid could not be demonstrated after ingestion of [1-13C]phytanic acid in a dose of 1 mg/kg body weight. In addition to phytanic acid accumulation (232 mumol/L), the chondrodysplasia punctata patient showed an elevated 2-hydroxyphytanic acid plasma concentration (0.4 mumol/L), whereas the plasma pristanic acid level was in the control range (0.7 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "In vivo study of phytanic acid alpha-oxidation in classic Refsum's disease and chondrodysplasia punctata. A series of in vivo experiments is described in which [1-13C]phytanic acid was given as an oral substrate to a healthy subject and two patients showing an impairment in phytanic acid degradation, one with Refsum's disease and one with chondrodysplasia punctata. After intake of the substrate by the control in a dose of 20 mg/kg body weight, the production of 13CO2 was measured in exhaled breath air and the concomitant formation of labeled 2-hydroxyphytanic acid and of pristanic acid was demonstrated by plasma analysis. After application of a substrate dose of 1 mg/kg body weight to the control, no substantial amounts of 13CO2 were measured, whereas time-dependent analysis of labeled 2-hydroxyphytanic acid in plasma yielded a concentration curve superimposed upon the baseline value (0.2 mumol/L) of the unlabeled substance. Phytanic acid accumulated in plasma from the Refsum's disease patient [649 mumol/L, controls > 1 y (n = 100): < 10 mumol/L], whereas the pristanic acid concentration was within the control range [1.4 mumol/L, controls > 1 y (n = 100): < 3 mumol/L]. Low amounts of 2-hydroxyphytanic acid were found normally present [0.04 mumol/L, controls > 1 y (n = 11): < 0.2 mumol/L], and formation of labeled 2-hydroxyphytanic acid could not be demonstrated after ingestion of [1-13C]phytanic acid in a dose of 1 mg/kg body weight. In addition to phytanic acid accumulation (232 mumol/L), the chondrodysplasia punctata patient showed an elevated 2-hydroxyphytanic acid plasma concentration (0.4 mumol/L), whereas the plasma pristanic acid level was in the control range (0.7 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282701", "title": "hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn.", "content": "We have previously isolated a protein from mouse liver nuclei that specifically binds to single stranded (TTAGGG)n repeats. TTAGGG is the telomeric repeats of mammals and we therefore named the new protein single stranded telomere binding protein (sTBP). Further studies now identify sTBP as heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 on the basis of amino acid sequence determination and antibody reactivity. A2 and B1 form a major part of the protein component of hnRNP particles and are abundant nuclear proteins. Unexpectedly, A2/B1 has a high specificity for binding to the RNA equivalent of TTAGGG, UUAGGG, but under the same conditions does not appear to have a strong affinity for a number of other RNA species.", "contents": "hnRNP A2/B1 binds specifically to single stranded vertebrate telomeric repeat TTAGGGn. We have previously isolated a protein from mouse liver nuclei that specifically binds to single stranded (TTAGGG)n repeats. TTAGGG is the telomeric repeats of mammals and we therefore named the new protein single stranded telomere binding protein (sTBP). Further studies now identify sTBP as heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 on the basis of amino acid sequence determination and antibody reactivity. A2 and B1 form a major part of the protein component of hnRNP particles and are abundant nuclear proteins. Unexpectedly, A2/B1 has a high specificity for binding to the RNA equivalent of TTAGGG, UUAGGG, but under the same conditions does not appear to have a strong affinity for a number of other RNA species."} {"id": "PMID:1282702", "title": "Recognition of the high affinity binding site in rev-response element RNA by the human immunodeficiency virus type-1 rev protein.", "content": "The Human Immunodeficiency Virus type-1 rev protein binds with high affinity to a bubble structure located within the rev-response element (RRE) RNA in stemloop II. After this initial interaction, additional rev molecules bind to the RRE RNA in an ordered assembly process which requires a functional bubble structure, since mutations in the bubble sequence that reduce rev affinity block multiple complex formation. We have used synthetic chemistry to characterize the interaction between rev protein and its high affinity binding site. A minimal synthetic duplex RNA (RBC6) carrying the bubble and 12 flanking base pairs is able to bind rev with 1 to 1 stoichiometry and with high affinity. When the bubble structure is inserted into synthetic RNA molecules carrying longer stretches of flanking double-stranded RNA, rev forms additional complexes resembling the multimers observed with the RRE RNA. The ability of rev to bind to RBC6 analogues containing functional group modifications on base and sugar moieties of nucleoside residues was also examined. The results provide strong evidence that the bubble structure contains specific configurations of non-Watson--Crick G:G and G:A base pairs and suggest that high affinity recognition of RRE RNA by rev requires hydrogen bonding to functional groups in the major groove of a distorted RNA structure.", "contents": "Recognition of the high affinity binding site in rev-response element RNA by the human immunodeficiency virus type-1 rev protein. The Human Immunodeficiency Virus type-1 rev protein binds with high affinity to a bubble structure located within the rev-response element (RRE) RNA in stemloop II. After this initial interaction, additional rev molecules bind to the RRE RNA in an ordered assembly process which requires a functional bubble structure, since mutations in the bubble sequence that reduce rev affinity block multiple complex formation. We have used synthetic chemistry to characterize the interaction between rev protein and its high affinity binding site. A minimal synthetic duplex RNA (RBC6) carrying the bubble and 12 flanking base pairs is able to bind rev with 1 to 1 stoichiometry and with high affinity. When the bubble structure is inserted into synthetic RNA molecules carrying longer stretches of flanking double-stranded RNA, rev forms additional complexes resembling the multimers observed with the RRE RNA. The ability of rev to bind to RBC6 analogues containing functional group modifications on base and sugar moieties of nucleoside residues was also examined. The results provide strong evidence that the bubble structure contains specific configurations of non-Watson--Crick G:G and G:A base pairs and suggest that high affinity recognition of RRE RNA by rev requires hydrogen bonding to functional groups in the major groove of a distorted RNA structure."} {"id": "PMID:1282703", "title": "Generation of viroid conformational isomers that are stable to incubation with magnesium ions and in a nuclear extract from tomato plants.", "content": "We identified conditions for heating and quick cooling viroid RNAs in the presence of salt which lead to the production of conformational isomers stable to incubation for at least 45 minutes at 30 degrees in the presence of magnesium ions. Elution in 0.3 M NaCl allowed the purification of an electrophoretically slow form of an in vitro transcript carrying a complete copy of the potato spindle tuber viroid RNA sequence. Slow forms of this transcript and of kinase-labeled linear viroid RNA persisted for longer than 20 minutes when incubated with a protein-rich extract prepared from the nuclei of uninfected tomato plants, although both were slowly cleaved by a nuclease present in this extract. The fast form of the transcript was highly resistant to this tomato ribonuclease. The slow form of the transcript was much more susceptible to cleavage by RNase T1 than the fast form of this RNA, suggesting that the reduced gel mobility of the slow forms results from their relatively open structure. The ability to purify viroid conformational isomers from polyacrylamide gels will facilitate biochemical studies aimed at identifying host components interacting with RNAs of the viroid replication complex, which may not all be present in the most thermodynamically favored rodlike structure of mature viroids.", "contents": "Generation of viroid conformational isomers that are stable to incubation with magnesium ions and in a nuclear extract from tomato plants. We identified conditions for heating and quick cooling viroid RNAs in the presence of salt which lead to the production of conformational isomers stable to incubation for at least 45 minutes at 30 degrees in the presence of magnesium ions. Elution in 0.3 M NaCl allowed the purification of an electrophoretically slow form of an in vitro transcript carrying a complete copy of the potato spindle tuber viroid RNA sequence. Slow forms of this transcript and of kinase-labeled linear viroid RNA persisted for longer than 20 minutes when incubated with a protein-rich extract prepared from the nuclei of uninfected tomato plants, although both were slowly cleaved by a nuclease present in this extract. The fast form of the transcript was highly resistant to this tomato ribonuclease. The slow form of the transcript was much more susceptible to cleavage by RNase T1 than the fast form of this RNA, suggesting that the reduced gel mobility of the slow forms results from their relatively open structure. The ability to purify viroid conformational isomers from polyacrylamide gels will facilitate biochemical studies aimed at identifying host components interacting with RNAs of the viroid replication complex, which may not all be present in the most thermodynamically favored rodlike structure of mature viroids."} {"id": "PMID:1282704", "title": "Large scale chemical synthesis, purification and crystallization of RNA-DNA chimeras.", "content": "RNA-DNA chimeras, in which both DNA and RNA monomers are site-specifically substituted in the same strand, may be prepared only by chemical synthesis. Biochemical studies have revealed a number of surprising and subtle effects resulting from the insertion of either a ribonucleotide into a DNA strand or a deoxyribonucleotide into an RNA strand. The availability of large quantities of these chimeras allows for their crystallization and subsequent x-ray structure determination. We describe a flexible and efficient method for the large-scale preparation of these compounds, their purification, and their crystallization. The methodology is based on a combination of existing DNA phosphoramidite synthons and those recently introduced for the preparation of biochemically active RNA1. We demonstrate that these two different synthons are compatible, produce large quantities of nucleic acid needed for physical studies, and that high resolution diffraction quality crystals may be grown from these chimeras. Of the duplex chimeras synthesized and crystallized, [r(G)d(CGTATACGC)]2, [d(GCGT)r(A)d(TACGC)]2 and [r(GCG)d(TATACCC) + d(GGGTATACGC)] form A-helices and d(CG)r(CG)d(CG)]2 forms a left-handed Z-helix.", "contents": "Large scale chemical synthesis, purification and crystallization of RNA-DNA chimeras. RNA-DNA chimeras, in which both DNA and RNA monomers are site-specifically substituted in the same strand, may be prepared only by chemical synthesis. Biochemical studies have revealed a number of surprising and subtle effects resulting from the insertion of either a ribonucleotide into a DNA strand or a deoxyribonucleotide into an RNA strand. The availability of large quantities of these chimeras allows for their crystallization and subsequent x-ray structure determination. We describe a flexible and efficient method for the large-scale preparation of these compounds, their purification, and their crystallization. The methodology is based on a combination of existing DNA phosphoramidite synthons and those recently introduced for the preparation of biochemically active RNA1. We demonstrate that these two different synthons are compatible, produce large quantities of nucleic acid needed for physical studies, and that high resolution diffraction quality crystals may be grown from these chimeras. Of the duplex chimeras synthesized and crystallized, [r(G)d(CGTATACGC)]2, [d(GCGT)r(A)d(TACGC)]2 and [r(GCG)d(TATACCC) + d(GGGTATACGC)] form A-helices and d(CG)r(CG)d(CG)]2 forms a left-handed Z-helix."} {"id": "PMID:1282705", "title": "The effect of loop size in antisense and target RNAs on the efficiency of antisense RNA control.", "content": "Most natural antisense RNAs display a high degree of secondary structure with stem-loops as their most prominent feature. Mutations affecting the inhibitory activity of these RNAs most often map in or close to loop regions in both the antisense and target RNAs. The primary recognition loops often contain 5-7 unpaired nucleotides. Nucleotide changes in the loops affect the binding rate and, hence, the inhibitory effect on the activity of the target RNA. Here we address the question whether loop sizes affect binding rates between antisense and target RNAs, using the replication control system of plasmid R1 as a model system. By creating a series of loop size mutants we show that loop size alterations have strong effects on the binding rates between the two reactant RNAs in vitro, and that most of the mutations analyzed display corresponding effects on antisense RNA control in vivo. Our data suggest that the three-dimensional structures of antisense and target RNA stem-loops are crucial for determining binding rates. The implications of these results for the design of efficient artificial antisense RNA control systems are discussed.", "contents": "The effect of loop size in antisense and target RNAs on the efficiency of antisense RNA control. Most natural antisense RNAs display a high degree of secondary structure with stem-loops as their most prominent feature. Mutations affecting the inhibitory activity of these RNAs most often map in or close to loop regions in both the antisense and target RNAs. The primary recognition loops often contain 5-7 unpaired nucleotides. Nucleotide changes in the loops affect the binding rate and, hence, the inhibitory effect on the activity of the target RNA. Here we address the question whether loop sizes affect binding rates between antisense and target RNAs, using the replication control system of plasmid R1 as a model system. By creating a series of loop size mutants we show that loop size alterations have strong effects on the binding rates between the two reactant RNAs in vitro, and that most of the mutations analyzed display corresponding effects on antisense RNA control in vivo. Our data suggest that the three-dimensional structures of antisense and target RNA stem-loops are crucial for determining binding rates. The implications of these results for the design of efficient artificial antisense RNA control systems are discussed."} {"id": "PMID:1282709", "title": "Effects of lordosis-relevant neuropeptides on midbrain periaqueductal gray neuronal activity in vitro.", "content": "Certain neuropeptides can facilitate lordosis by acting on midbrain periaqueductal gray (PAG) in estrogen-primed female rats. Here, we investigated responses of individual PAG neurons in vitro, to five neuropeptides: substance P (SP), luteinizing hormone-releasing hormone (LHRH), prolactin (PRL), oxytocin (OT), and thyrotropin-releasing hormone (TRH). Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way. Oxytocin acted through oxytocin receptors located on the recorded PAG neurons, since excitatory actions of OT were 1) not abolished by synaptic blockade, 2) mimicked by the OT-specific agonist [Thr4, Gly7]OT but not by arginine vasopressin, and 3) blocked by the OT-specific antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin. Although LHRH had no neurotransmitter-like action on spontaneous activity of PAG neurons, it, as well as SP, could modulate responses of some dorsal PAG neurons to GABAA and GABAB agonists or norepinephrine. Neuromodulatory actions of LHRH and SP could help facilitate lordosis through PAG neurons.", "contents": "Effects of lordosis-relevant neuropeptides on midbrain periaqueductal gray neuronal activity in vitro. Certain neuropeptides can facilitate lordosis by acting on midbrain periaqueductal gray (PAG) in estrogen-primed female rats. Here, we investigated responses of individual PAG neurons in vitro, to five neuropeptides: substance P (SP), luteinizing hormone-releasing hormone (LHRH), prolactin (PRL), oxytocin (OT), and thyrotropin-releasing hormone (TRH). Substance P, OT, and TRH excited spontaneous activity of PAG neurons through neurotransmitter-like actions in a dose-dependent manner, whereas LHRH and PRL virtually never affected PAG neurons this way. Oxytocin acted through oxytocin receptors located on the recorded PAG neurons, since excitatory actions of OT were 1) not abolished by synaptic blockade, 2) mimicked by the OT-specific agonist [Thr4, Gly7]OT but not by arginine vasopressin, and 3) blocked by the OT-specific antagonist [d(CH2)5,Tyr(Me)2,Orn8]vasotocin. Although LHRH had no neurotransmitter-like action on spontaneous activity of PAG neurons, it, as well as SP, could modulate responses of some dorsal PAG neurons to GABAA and GABAB agonists or norepinephrine. Neuromodulatory actions of LHRH and SP could help facilitate lordosis through PAG neurons."} {"id": "PMID:1282710", "title": "[Palliative methods of the treatment of prostatic adenoma].", "content": "Semi-conservative therapies in prostatic adenoma are discussed. They may be used in patients with non-operational prostatic adenoma. Besides permanent catheterization, there are the following possibilities: extension of the prostatic tube with a balloon, application of the urologic coil, commissurotomy, therapy with cryosurgery or hyperthermia. ++Palliative therapy markedly prolongs and improves the life of patients with systemic diseases, which make radical surgery impossible.", "contents": "[Palliative methods of the treatment of prostatic adenoma]. Semi-conservative therapies in prostatic adenoma are discussed. They may be used in patients with non-operational prostatic adenoma. Besides permanent catheterization, there are the following possibilities: extension of the prostatic tube with a balloon, application of the urologic coil, commissurotomy, therapy with cryosurgery or hyperthermia. ++Palliative therapy markedly prolongs and improves the life of patients with systemic diseases, which make radical surgery impossible."} {"id": "PMID:1282711", "title": "[Preliminary clinical evaluation of systemic chemotherapy of invasive cancer of the bladder by the CMV protocol].", "content": "The authors discuss the results of preliminary clinical trials with chemotherapy with CMV (cisplatin, methotrexate, vinblastine) in the group of 17 patients with the infiltrating cancer of the bladder. Chemotherapy was used as an element of the radical treatment (in 7 patients, i.e. 41.2%) or as ++palliative treatment (in 10 patients, i.e. 58.8%). Objective response to the treatment was noted in 73.3% of the treated patients, including 13.3% of the complete recovery, and 60.0% of partial improvement. In the remaining 26.7% of patients (including all patients with distant metastases) no response to therapy was achieved. Complications of therapy are discussed. Systemic chemotherapy with CMV regimen proved efficient in the infiltrating cancer of the bladder.", "contents": "[Preliminary clinical evaluation of systemic chemotherapy of invasive cancer of the bladder by the CMV protocol]. The authors discuss the results of preliminary clinical trials with chemotherapy with CMV (cisplatin, methotrexate, vinblastine) in the group of 17 patients with the infiltrating cancer of the bladder. Chemotherapy was used as an element of the radical treatment (in 7 patients, i.e. 41.2%) or as ++palliative treatment (in 10 patients, i.e. 58.8%). Objective response to the treatment was noted in 73.3% of the treated patients, including 13.3% of the complete recovery, and 60.0% of partial improvement. In the remaining 26.7% of patients (including all patients with distant metastases) no response to therapy was achieved. Complications of therapy are discussed. Systemic chemotherapy with CMV regimen proved efficient in the infiltrating cancer of the bladder."} {"id": "PMID:1282712", "title": "[Evaluation of the results of combined treatment of patients with testicular seminoma in the II stage of clinical advancement].", "content": "An attempt to introduce combined therapy for patients with testicular seminoma in the II degree of clinical advancement was undertaken at the Centre of Oncology. Combined therapy consisted of 3 courses of PVB in the following daily doses: DDP 100 mg/m2 i.v. on the first day; VLB 10 mg i.v. on the first and second day; bleomycin 30 mg i.v. on the second, ninth and sixteenth day every 21 days, and 60Co on lymphatic glands area in which metastases were diagnosed prior to chemotherapy. Twenty three patients were treated that way between January 1985 and June 1989. Mean follow-up period after the treatment was 14 months. One patient died for the tumor, metastases to the lungs were diagnosed in one patient 9 months after completion of the treatment which ameliorated after \"second\" chemotherapy, and 22 patients (96%) are still free from the symptoms of active disease.", "contents": "[Evaluation of the results of combined treatment of patients with testicular seminoma in the II stage of clinical advancement]. An attempt to introduce combined therapy for patients with testicular seminoma in the II degree of clinical advancement was undertaken at the Centre of Oncology. Combined therapy consisted of 3 courses of PVB in the following daily doses: DDP 100 mg/m2 i.v. on the first day; VLB 10 mg i.v. on the first and second day; bleomycin 30 mg i.v. on the second, ninth and sixteenth day every 21 days, and 60Co on lymphatic glands area in which metastases were diagnosed prior to chemotherapy. Twenty three patients were treated that way between January 1985 and June 1989. Mean follow-up period after the treatment was 14 months. One patient died for the tumor, metastases to the lungs were diagnosed in one patient 9 months after completion of the treatment which ameliorated after \"second\" chemotherapy, and 22 patients (96%) are still free from the symptoms of active disease."} {"id": "PMID:1282715", "title": "[Methotrexate-induced skin detachment].", "content": "The undesirable effects of high-dose methotrexate on integument and mucosa are well-known, but lesions of the skin proper, characterized by distal erythema with desquamation, are rare. We report the case of a male patient presenting with extensive skin erosions after intravenous infusion of a 5 gram total dose of methotrexate to treat high-grade lymphoma. The skin disease was accompanied by renal, hepatic and mucosal lesions, as well as bone marrow aplasia. The mechanism of cutaneous necrosis is uncertain, but it might be due to direct toxicity of methotrexate to the epidermis. The patient was also treated with G-CSF. He recovered from aplasia within 6 days, without infectious complications. Haematopoietic growth factors might have reduced the risk of infection arising from the skin, by shortening the duration of cytopenia.", "contents": "[Methotrexate-induced skin detachment]. The undesirable effects of high-dose methotrexate on integument and mucosa are well-known, but lesions of the skin proper, characterized by distal erythema with desquamation, are rare. We report the case of a male patient presenting with extensive skin erosions after intravenous infusion of a 5 gram total dose of methotrexate to treat high-grade lymphoma. The skin disease was accompanied by renal, hepatic and mucosal lesions, as well as bone marrow aplasia. The mechanism of cutaneous necrosis is uncertain, but it might be due to direct toxicity of methotrexate to the epidermis. The patient was also treated with G-CSF. He recovered from aplasia within 6 days, without infectious complications. Haematopoietic growth factors might have reduced the risk of infection arising from the skin, by shortening the duration of cytopenia."} {"id": "PMID:1282713", "title": "[Evaluation of the effectiveness of prazosin in conservative treatment of benign prostatic hypertrophy].", "content": "Prazosin--a selective blocker of alpha 1-adrenergic receptors--was administered to 30 patients with benign prostatic hypertrophy. Twenty four patients (80%) reported an improvement in voiding and observed more potent urinary stream after the treatment. Average and maximum flow rates increased in 18 patients (60%). Therapy had to be discontinued in 2 patients because of the adverse reactions (hypotension and syncope in one and exacerbation of the coronary disease symptoms in another patient).", "contents": "[Evaluation of the effectiveness of prazosin in conservative treatment of benign prostatic hypertrophy]. Prazosin--a selective blocker of alpha 1-adrenergic receptors--was administered to 30 patients with benign prostatic hypertrophy. Twenty four patients (80%) reported an improvement in voiding and observed more potent urinary stream after the treatment. Average and maximum flow rates increased in 18 patients (60%). Therapy had to be discontinued in 2 patients because of the adverse reactions (hypotension and syncope in one and exacerbation of the coronary disease symptoms in another patient)."} {"id": "PMID:1282716", "title": "[Monoclonal antibodies in the treatment of rheumatoid arthritis].", "content": "Monoclonal antibodies (MoAb's) make it possible to treat rheumatoid arthritis with selective immunotherapy. These antibodies may be directed against various targets, such as lymphocyte activation antigens, cytokines or subpopulations of lymphocytes (notably TCD4 +), involved in the pathogenesis of the disease. Recent open studies have demonstrated the feasibility and safety of this therapeutic method, but the number of patients who entered the trials is still low, and the clinical, biological and immunological results vary considerably in importance and duration, without remission. No response predictive factor could be elicited from these studies. The murine origin of these MoAb's exposes to the frequent risk of immunization which may interfere with the effectiveness and safety of a second treatment. Some possibilities can already be envisaged, including potentiation of the MoAb by coupling with a cytotoxic agent (anti-CD5 + ricin) and \"humanization\" of murine MoAb's (chimeric anti-CD4) reducing the risk of immunization. Further (controlled) trials therefore are indispensable to evaluate the true rank occupied by this therapeutic method in rheumatoid arthritis.", "contents": "[Monoclonal antibodies in the treatment of rheumatoid arthritis]. Monoclonal antibodies (MoAb's) make it possible to treat rheumatoid arthritis with selective immunotherapy. These antibodies may be directed against various targets, such as lymphocyte activation antigens, cytokines or subpopulations of lymphocytes (notably TCD4 +), involved in the pathogenesis of the disease. Recent open studies have demonstrated the feasibility and safety of this therapeutic method, but the number of patients who entered the trials is still low, and the clinical, biological and immunological results vary considerably in importance and duration, without remission. No response predictive factor could be elicited from these studies. The murine origin of these MoAb's exposes to the frequent risk of immunization which may interfere with the effectiveness and safety of a second treatment. Some possibilities can already be envisaged, including potentiation of the MoAb by coupling with a cytotoxic agent (anti-CD5 + ricin) and \"humanization\" of murine MoAb's (chimeric anti-CD4) reducing the risk of immunization. Further (controlled) trials therefore are indispensable to evaluate the true rank occupied by this therapeutic method in rheumatoid arthritis."} {"id": "PMID:1282717", "title": "Search for the stable state of a short chain in a molecular field.", "content": "A general approach is developed to search for stable structures of short chain fragments (e.g. of loops or bound oligopeptides) in a given molecular field. This molecular field is produced by the remaining part of a globule or by any other surface with a defined spatial structure. The fragment must be short enough to have no pronounced long-range interactions within itself. The method is illustrated by calculation of the 3-D structures of two loops of bovine pancreatic trypsin inhibitor (BPTI). Computations are based on a lattice model of conformational space and on strict and fast algorithms of 1-D statistical mechanics and dynamic programming (which are very similar in essence). This makes a search of oligopeptide structures only several times (and not several orders of magnitude) longer than that of a dipeptide.", "contents": "Search for the stable state of a short chain in a molecular field. A general approach is developed to search for stable structures of short chain fragments (e.g. of loops or bound oligopeptides) in a given molecular field. This molecular field is produced by the remaining part of a globule or by any other surface with a defined spatial structure. The fragment must be short enough to have no pronounced long-range interactions within itself. The method is illustrated by calculation of the 3-D structures of two loops of bovine pancreatic trypsin inhibitor (BPTI). Computations are based on a lattice model of conformational space and on strict and fast algorithms of 1-D statistical mechanics and dynamic programming (which are very similar in essence). This makes a search of oligopeptide structures only several times (and not several orders of magnitude) longer than that of a dipeptide."} {"id": "PMID:1282718", "title": "A new lease of life. Nursing care of elderly surgical patients.", "content": "Advances in surgical techniques have meant more elderly people can now be operated on. Older people are, however, more prone to postoperative complications and require greater preoperative preparation. Forward planning and setting high standards for nursing care are prerequisites in this area of care.", "contents": "A new lease of life. Nursing care of elderly surgical patients. Advances in surgical techniques have meant more elderly people can now be operated on. Older people are, however, more prone to postoperative complications and require greater preoperative preparation. Forward planning and setting high standards for nursing care are prerequisites in this area of care."} {"id": "PMID:1282720", "title": "The molecular biology of human hereditary central diabetes insipidus.", "content": "Molecular biology techniques have begun to shed light on the genetic basis of autosomal dominant central DI, but several very basic questions remain to be answered. The disorder was initially presumed to have a developmental, degenerative, or autoimmune basis based on the autopsy findings in the hypothalamus of a limited number of patients. The molecular cloning of the AVP-NP II gene and the clue from the Brattleboro rat that at least this one form of hereditary DI involved an AVP-NP II gene mutation allowed us to focus on this gene in our study of human hereditary DI. Our initial experiments did not show this gene to have a major structural alteration such as a deletion, insertion, or rearrangement, but the approach was not capable of detecting more suitable defects. The linkage studies provided substantial evidence that one particular OT-NP I haplotype was linked to the disease phenotype in each family, and thus, a mutation in the AVP/OT region of chromosome 20 is responsible for this disease. Ito et al. (1991) then identified a single base change in the AVP-NP II gene in affected members of one Japanese family. This change was not detected in unrelated, unaffected persons and thus is a good candidate for the mutation causing the disease in this family. However, there appears to be diversity in the molecular basis of autosomal dominant central DI as affected members of one of our families did not have this particular base change in either AVP-NP II allele and recently another distinct AVP-NP II gene base change has been associated with this disorder. One interesting question still to be addressed is how a mutation in the NP-II coding region of this gene prevents AVP release from the posterior pituitary in the rat or the human disease. Does the disrupted AVP-NP II coding sequence prevent normal processing of the mRNA so that it can not be properly translated into protein? Does the mutated AVP-NP II glycoprotein precursor protein interfere with normal post-translational processing to prevent release of AVP? Is an altered NP II protein not able to protect the AVP from proteolysis within the magnocellular neuron? An even more puzzling question is how a mutation in the gene encoding a hormone is inherited in an autosomal dominant pattern. The Brattleboro rat model follows the a priori expectation of autosomal recessive inheritance: the animal only exhibits a defect in hormone function if both genes encoding the hormone are defective.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "The molecular biology of human hereditary central diabetes insipidus. Molecular biology techniques have begun to shed light on the genetic basis of autosomal dominant central DI, but several very basic questions remain to be answered. The disorder was initially presumed to have a developmental, degenerative, or autoimmune basis based on the autopsy findings in the hypothalamus of a limited number of patients. The molecular cloning of the AVP-NP II gene and the clue from the Brattleboro rat that at least this one form of hereditary DI involved an AVP-NP II gene mutation allowed us to focus on this gene in our study of human hereditary DI. Our initial experiments did not show this gene to have a major structural alteration such as a deletion, insertion, or rearrangement, but the approach was not capable of detecting more suitable defects. The linkage studies provided substantial evidence that one particular OT-NP I haplotype was linked to the disease phenotype in each family, and thus, a mutation in the AVP/OT region of chromosome 20 is responsible for this disease. Ito et al. (1991) then identified a single base change in the AVP-NP II gene in affected members of one Japanese family. This change was not detected in unrelated, unaffected persons and thus is a good candidate for the mutation causing the disease in this family. However, there appears to be diversity in the molecular basis of autosomal dominant central DI as affected members of one of our families did not have this particular base change in either AVP-NP II allele and recently another distinct AVP-NP II gene base change has been associated with this disorder. One interesting question still to be addressed is how a mutation in the NP-II coding region of this gene prevents AVP release from the posterior pituitary in the rat or the human disease. Does the disrupted AVP-NP II coding sequence prevent normal processing of the mRNA so that it can not be properly translated into protein? Does the mutated AVP-NP II glycoprotein precursor protein interfere with normal post-translational processing to prevent release of AVP? Is an altered NP II protein not able to protect the AVP from proteolysis within the magnocellular neuron? An even more puzzling question is how a mutation in the gene encoding a hormone is inherited in an autosomal dominant pattern. The Brattleboro rat model follows the a priori expectation of autosomal recessive inheritance: the animal only exhibits a defect in hormone function if both genes encoding the hormone are defective.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282721", "title": "Effect of bradykinin on the cytosolic free calcium activity and phosphoinositol turnover in human glomerular epithelial cells.", "content": "The effect of bradykinin (BK) on the intracellular free calcium activity [Ca2+]i and phosphoinositide (PI) turnover was investigated in human glomerular epithelial cells (GEC) in culture. Human GEC exhibited a baseline [Ca2+]i of 114 +/- 3 nmol (n = 81). BK (ED50 10(-9) mol/l) caused a rapid and transient increase in [Ca2+]i, which could also be observed in the absence of extracellular calcium. The effect of BK (10(-8) mol/l) on the [Ca2+]i was inhibited by the BK2 antagonist Hoe 140 (IC50 10(-8) mol/l). BK also induced PI turnover in a time- and dose-dependent manner. A transient increase in (1,4,5)-inositol-triphosphate (InsP3) formation from 1,445 +/- 119 to 4,629 +/- 323 cpm occurred after 5 s. Stimulation of protein kinase C (PKC) by short-term preincubation (15 min) of human GEC with phorbol-12-myristate-13-acetate (PMA) induced a dose-dependent inhibition of the BK-stimulated (10(-7) mol/l) inositol-phosphate formation. Downregulation of PKC by preincubation of human GEC with PMA (24 h, 10(-6) mol/l) or inhibition of PKC by pretreatment with staurosporin (1 h, 10(-6) mol/l) resulted in a slight but significant augmentation of the BK-induced InsP3 stimulation. The data indicate that BK induces stimulation of [Ca2+]i and PI turnover via a BK2 receptor in human GEC. PKC might exert a negative feedback function for the BK-induced PI turnover.", "contents": "Effect of bradykinin on the cytosolic free calcium activity and phosphoinositol turnover in human glomerular epithelial cells. The effect of bradykinin (BK) on the intracellular free calcium activity [Ca2+]i and phosphoinositide (PI) turnover was investigated in human glomerular epithelial cells (GEC) in culture. Human GEC exhibited a baseline [Ca2+]i of 114 +/- 3 nmol (n = 81). BK (ED50 10(-9) mol/l) caused a rapid and transient increase in [Ca2+]i, which could also be observed in the absence of extracellular calcium. The effect of BK (10(-8) mol/l) on the [Ca2+]i was inhibited by the BK2 antagonist Hoe 140 (IC50 10(-8) mol/l). BK also induced PI turnover in a time- and dose-dependent manner. A transient increase in (1,4,5)-inositol-triphosphate (InsP3) formation from 1,445 +/- 119 to 4,629 +/- 323 cpm occurred after 5 s. Stimulation of protein kinase C (PKC) by short-term preincubation (15 min) of human GEC with phorbol-12-myristate-13-acetate (PMA) induced a dose-dependent inhibition of the BK-stimulated (10(-7) mol/l) inositol-phosphate formation. Downregulation of PKC by preincubation of human GEC with PMA (24 h, 10(-6) mol/l) or inhibition of PKC by pretreatment with staurosporin (1 h, 10(-6) mol/l) resulted in a slight but significant augmentation of the BK-induced InsP3 stimulation. The data indicate that BK induces stimulation of [Ca2+]i and PI turnover via a BK2 receptor in human GEC. PKC might exert a negative feedback function for the BK-induced PI turnover."} {"id": "PMID:1282722", "title": "Inhibition of sodium-dependent transport systems in LLC-PK1 cells by metabolites of ifosfamide.", "content": "Ifosfamide (IF) is an alkylating cytostatic derived from nitrogen mustard. In addition to its well-known urotoxic effects (hemorrhagic cystitis), several cases of Fanconi syndrome following IF therapy have been reported. No information is available concerning the pathomechanisms of this tubulotoxicity. We used the permanent renal epithelial cell line LLC-PK1 in order to investigate whether major metabolites of IF (i.e. 4-OH-IF, acrolein and chloracetyldehyde) induced the transport defects most frequently detected after IF therapy in vivo. LLC-PK1 cells of passages 162-177, grown in plastic culture dishes, were used in a confluent state. Sodium-dependent and independent fluxes of l-[3H]alanine and of D-[3H]glucose were determined by standard techniques. Activities of marker enzymes of apical and basolateral membranes, of mitochondria and of endoplasmic reticulum were determined in cell homogenates. IF itself has no detectable effect on fluxes of l-alanine and D-glucose in LLC-PK1 cells. The IF metabolite 4-OOH-IF induces a clear inhibition of sodium-dependent fluxes of both substrates after a 24-hour exposure of cells to 100 mumol/l of 4-OOH-IF. Chloracetaldehyde induces a biphasic response of sodium-dependent fluxes of l-alanine with increased uptake rates at low concentrations (< 200 mumol/l) and with a short incubation time, while higher concentrations and long exposure of the cells leads to a reduction in sodium coupled transport. Glucose transport is affected in a comparable way, however, in contrast to alanine transport, chloracetaldehyde also stimulates sodium-independent fluxes of glucose. Acrolein is the most toxic substance tested. It severely damages cell monolayers at concentrations beyond 75 mumol/l. Sodium-coupled glucose and alanine transport is inhibited by acrolein at concentrations higher than 50 mumol/l. Sodium-coupled glucose transport is more sensitive to all metabolites tested than alanine transport. While acrolein strongly affects both transport systems, marker enzymes of the apical plasma membrane, i.e. alkaline phosphatase and leucine amino-peptidase, are not significantly inhibited, suggesting a specificity of the toxic effect for the transport proteins. We conclude that LLC-PK1 cells represent a good model for further investigation of the pathogenesis of Fanconi syndrome after IF therapy. Sodium-dependent transport systems are more sensitive to acrolein than other cell surface proteins.", "contents": "Inhibition of sodium-dependent transport systems in LLC-PK1 cells by metabolites of ifosfamide. Ifosfamide (IF) is an alkylating cytostatic derived from nitrogen mustard. In addition to its well-known urotoxic effects (hemorrhagic cystitis), several cases of Fanconi syndrome following IF therapy have been reported. No information is available concerning the pathomechanisms of this tubulotoxicity. We used the permanent renal epithelial cell line LLC-PK1 in order to investigate whether major metabolites of IF (i.e. 4-OH-IF, acrolein and chloracetyldehyde) induced the transport defects most frequently detected after IF therapy in vivo. LLC-PK1 cells of passages 162-177, grown in plastic culture dishes, were used in a confluent state. Sodium-dependent and independent fluxes of l-[3H]alanine and of D-[3H]glucose were determined by standard techniques. Activities of marker enzymes of apical and basolateral membranes, of mitochondria and of endoplasmic reticulum were determined in cell homogenates. IF itself has no detectable effect on fluxes of l-alanine and D-glucose in LLC-PK1 cells. The IF metabolite 4-OOH-IF induces a clear inhibition of sodium-dependent fluxes of both substrates after a 24-hour exposure of cells to 100 mumol/l of 4-OOH-IF. Chloracetaldehyde induces a biphasic response of sodium-dependent fluxes of l-alanine with increased uptake rates at low concentrations (< 200 mumol/l) and with a short incubation time, while higher concentrations and long exposure of the cells leads to a reduction in sodium coupled transport. Glucose transport is affected in a comparable way, however, in contrast to alanine transport, chloracetaldehyde also stimulates sodium-independent fluxes of glucose. Acrolein is the most toxic substance tested. It severely damages cell monolayers at concentrations beyond 75 mumol/l. Sodium-coupled glucose and alanine transport is inhibited by acrolein at concentrations higher than 50 mumol/l. Sodium-coupled glucose transport is more sensitive to all metabolites tested than alanine transport. While acrolein strongly affects both transport systems, marker enzymes of the apical plasma membrane, i.e. alkaline phosphatase and leucine amino-peptidase, are not significantly inhibited, suggesting a specificity of the toxic effect for the transport proteins. We conclude that LLC-PK1 cells represent a good model for further investigation of the pathogenesis of Fanconi syndrome after IF therapy. Sodium-dependent transport systems are more sensitive to acrolein than other cell surface proteins."} {"id": "PMID:1282723", "title": "Tumor necrosis factor-alpha- and interleukin-1-stimulated intercellular adhesion molecule-1 expression by murine renal tubular epithelial cells is transcriptionally regulated and involves protein kinase C.", "content": "The regulation of intercellular adhesion molecule-1 (ICAM-1) expression by renal tubular epithelial cells (TEC) has been studied in vitro. ICAM-1 expression in TEC is stimulated with phorbol 12-myristate 13-acetate (PMA), but not with forskolin, suggesting a role for protein kinase C (PKC) but not for protein kinase A (PKA). The tumor necrosis factor-alpha- (TNF-alpha) and interleukin-1 (IL-1)-stimulated ICAM-1 expression in TEC is blocked with the PKC/PKA inhibitor staurosporine, and also with the PKC-selective inhibitor calphostin C. The TNF-alpha-stimulated ICAM-1 expression is resistant however to downregulation of PKC with PMA. The TNF-alpha- and IL-1-stimulated ICAM-1 expression is also inhibited with the transcriptional inhibitor actinomycin D and with the protein synthesis inhibitor cycloheximide. Thus, ICAM-1 expression by TEC may involve a downregulation-resistant PKC which induces ICAM-1 expression at a transcriptional level.", "contents": "Tumor necrosis factor-alpha- and interleukin-1-stimulated intercellular adhesion molecule-1 expression by murine renal tubular epithelial cells is transcriptionally regulated and involves protein kinase C. The regulation of intercellular adhesion molecule-1 (ICAM-1) expression by renal tubular epithelial cells (TEC) has been studied in vitro. ICAM-1 expression in TEC is stimulated with phorbol 12-myristate 13-acetate (PMA), but not with forskolin, suggesting a role for protein kinase C (PKC) but not for protein kinase A (PKA). The tumor necrosis factor-alpha- (TNF-alpha) and interleukin-1 (IL-1)-stimulated ICAM-1 expression in TEC is blocked with the PKC/PKA inhibitor staurosporine, and also with the PKC-selective inhibitor calphostin C. The TNF-alpha-stimulated ICAM-1 expression is resistant however to downregulation of PKC with PMA. The TNF-alpha- and IL-1-stimulated ICAM-1 expression is also inhibited with the transcriptional inhibitor actinomycin D and with the protein synthesis inhibitor cycloheximide. Thus, ICAM-1 expression by TEC may involve a downregulation-resistant PKC which induces ICAM-1 expression at a transcriptional level."} {"id": "PMID:1282724", "title": "Transmembrane signalling of cholinergic-stimulated contraction in isolated rat glomeruli.", "content": "Exposure of isolated rat glomeruli to carbachol (Carb) 1 mM induces glomerular (mesangial cell) contraction which is inhibited by pirenzepine. To identify the cellular signalling mechanism, we analyzed Carb-activated phosphoinositide hydrolysis in myo-[2-3H] inositol preloaded cells of isolated rat glomeruli. Carb evoked a rapid (5 s, 30.4 +/- 8.3% of basal) and sustained (60 s, 157.2 +/- 1.2% of basal) inositol trisphosphate (IP3) response. Acetylcholine 100 microM (Ach) in the presence of eserine also evoked IP3 formation. Mobilization of Ca2+ was monitored by preloading glomerular cells with 45Ca2+ (200 microCi/ml) and analyzing the cellular efflux using a constant perifusion system. Both Carb and Ach induced transient 45Ca2+ efflux, with peak values above baseline of 69.0 +/- 19.9 and 71.5 +/- 7.9%, respectively. Incubation with pirenzepine or prior release of Ca2+ from an IP3-sensitive intracellular pool by Thapsigargin (2 microM) prevented Carb-evoked Ca2+ release (100 and 60%, respectively). Therefore, glomerular cells possess functional cholinergic receptors which stimulate contraction via IP3-mediated intracellular Ca2+ release.", "contents": "Transmembrane signalling of cholinergic-stimulated contraction in isolated rat glomeruli. Exposure of isolated rat glomeruli to carbachol (Carb) 1 mM induces glomerular (mesangial cell) contraction which is inhibited by pirenzepine. To identify the cellular signalling mechanism, we analyzed Carb-activated phosphoinositide hydrolysis in myo-[2-3H] inositol preloaded cells of isolated rat glomeruli. Carb evoked a rapid (5 s, 30.4 +/- 8.3% of basal) and sustained (60 s, 157.2 +/- 1.2% of basal) inositol trisphosphate (IP3) response. Acetylcholine 100 microM (Ach) in the presence of eserine also evoked IP3 formation. Mobilization of Ca2+ was monitored by preloading glomerular cells with 45Ca2+ (200 microCi/ml) and analyzing the cellular efflux using a constant perifusion system. Both Carb and Ach induced transient 45Ca2+ efflux, with peak values above baseline of 69.0 +/- 19.9 and 71.5 +/- 7.9%, respectively. Incubation with pirenzepine or prior release of Ca2+ from an IP3-sensitive intracellular pool by Thapsigargin (2 microM) prevented Carb-evoked Ca2+ release (100 and 60%, respectively). Therefore, glomerular cells possess functional cholinergic receptors which stimulate contraction via IP3-mediated intracellular Ca2+ release."} {"id": "PMID:1282725", "title": "Role of prostacyclin in the renal response to acetylcholine.", "content": "Renal arterial infusion of acetylcholine (ACh; 40 micrograms/min) in control dogs produced a sustained rise in urinary sodium excretion (UNa V) and in renal plasma flow (RPF). When prostaglandin (PG) synthesis was inhibited with indomethacin (5 mg/kg), ACh produced only a transient rise in UNa V and RPF followed by a progressive decline in UNa V and RPF. Renal arterial infusion of PGI2 (0.2 microgram/min) restored the response to ACh to normal in indomethacin-treated dogs. The RPF was 84 +/- 9 ml/min during control and increased to 132 +/- 19 ml/min with the infusion of PGI2 (p < 0.01). RPF increased further to 188 +/- 18 ml/min at 20-min infusion of ACh and was maintained at 189 +/- 14 ml/min at 100-min infusion of ACh (p < 0.01). Our data suggest that the initial rise in RPF by ACh is independent of the PG system, whereas maintenance of the rise in RPF by ACh requires an intact synthesis of PGs, presumably PGI2 synthesized in the vascular tissues.", "contents": "Role of prostacyclin in the renal response to acetylcholine. Renal arterial infusion of acetylcholine (ACh; 40 micrograms/min) in control dogs produced a sustained rise in urinary sodium excretion (UNa V) and in renal plasma flow (RPF). When prostaglandin (PG) synthesis was inhibited with indomethacin (5 mg/kg), ACh produced only a transient rise in UNa V and RPF followed by a progressive decline in UNa V and RPF. Renal arterial infusion of PGI2 (0.2 microgram/min) restored the response to ACh to normal in indomethacin-treated dogs. The RPF was 84 +/- 9 ml/min during control and increased to 132 +/- 19 ml/min with the infusion of PGI2 (p < 0.01). RPF increased further to 188 +/- 18 ml/min at 20-min infusion of ACh and was maintained at 189 +/- 14 ml/min at 100-min infusion of ACh (p < 0.01). Our data suggest that the initial rise in RPF by ACh is independent of the PG system, whereas maintenance of the rise in RPF by ACh requires an intact synthesis of PGs, presumably PGI2 synthesized in the vascular tissues."} {"id": "PMID:1282728", "title": "Effects of galanin on the secretory activity of the rat adrenal cortex: in vivo and in vitro studies.", "content": "Galanin, a 28-amino-acid peptide originally isolated from pig intestine, was found to cause dose-dependent rises in the plasma concentration of corticosterone in hypophysectomized rats and in both basal and submaximally ACTH-stimulated in vitro corticosterone production by adrenal quarters and isolated zona fasciculata/reticularis cells. These findings indicate that galanin exerts a direct glucocorticoid secretagogue effect on the inner adrenocortical zones and suggest that galanin, high concentrations of which are contained in adrenal chromaffin cells, may be included in that group of regulatory peptides, by way of which adrenal zona medullaris is thought to exert a paracrine control on the function of the zona corticalis. Galanin was also found to increase the plasma level of aldosterone in hypophysectomized rats in a dose-dependent manner without inducing changes in natremia, kalemia, plasma renin activity, or ACTH plasma concentration. Galanin did enhance both basal aldosterone output and that following submaximal ACTH or angiotensin II stimulation aldosterone output from adrenal quarters, but not from isolated zona glomerulosa cells. This last, rather unexpected, result suggests that galanin exerts an indirect mineralocorticoid secretagogue action, which seems to require the structural integrity of the adrenal cortex and the presence of the adrenal medulla. The hypothesis is advanced that galanin may control the release of some medullary peptides, which in turn may affect mineralocorticoid secretion of the zona glomerulosa in a paracrine manner.", "contents": "Effects of galanin on the secretory activity of the rat adrenal cortex: in vivo and in vitro studies. Galanin, a 28-amino-acid peptide originally isolated from pig intestine, was found to cause dose-dependent rises in the plasma concentration of corticosterone in hypophysectomized rats and in both basal and submaximally ACTH-stimulated in vitro corticosterone production by adrenal quarters and isolated zona fasciculata/reticularis cells. These findings indicate that galanin exerts a direct glucocorticoid secretagogue effect on the inner adrenocortical zones and suggest that galanin, high concentrations of which are contained in adrenal chromaffin cells, may be included in that group of regulatory peptides, by way of which adrenal zona medullaris is thought to exert a paracrine control on the function of the zona corticalis. Galanin was also found to increase the plasma level of aldosterone in hypophysectomized rats in a dose-dependent manner without inducing changes in natremia, kalemia, plasma renin activity, or ACTH plasma concentration. Galanin did enhance both basal aldosterone output and that following submaximal ACTH or angiotensin II stimulation aldosterone output from adrenal quarters, but not from isolated zona glomerulosa cells. This last, rather unexpected, result suggests that galanin exerts an indirect mineralocorticoid secretagogue action, which seems to require the structural integrity of the adrenal cortex and the presence of the adrenal medulla. The hypothesis is advanced that galanin may control the release of some medullary peptides, which in turn may affect mineralocorticoid secretion of the zona glomerulosa in a paracrine manner."} {"id": "PMID:1282726", "title": "Endothelin-3 modulates glomerular filtration rate in the isolated perfused rat kidney.", "content": "The present study has been performed to evaluate hemodynamic and tubular effects of various endothelin-3 (ET-3) concentrations on the isolated perfused rat kidney. Using this experimental system we observed a profound reduction of renal perfusate flow at all ET-3 concentrations tested (50, 250 and 500 pmol/l), suggesting that the vasoconstrictive potency of ET-3 in the kidney is comparable to that described for endothelin-1 (ET-1). The effects on glomerular filtration rate (GFR) differed depending on the ET-3 dose applied. While 250 pmol/l ET-3 increased GFR by 30%, 500 pmol/l ET-3 markedly reduced GFR. 50 pmol/l ET-3 did not alter GFR although renal vascular resistance significantly increased. Infusion of 1 mumol/l N-nitro-L-arginine, a specific and potent inhibitor of nitric oxide synthesis in endothelial cells, abolished the GFR elevation induced by 250 pmol/l ET-3. In parallel with the changes of GFR we observed an increase in sodium reabsorption at 250 pmol/l and a decrease of this parameter at 500 pmol/l ET-3. Moreover, an ET-3 concentration (500 pmol/l), which induced a dramatic fall in tubular sodium load, led to an increase of fractional sodium excretion and to a decrease of renal oxygen consumption. We conclude that ET-3 is a potent vasoconstrictor in the isolated perfused rat kidney. Furthermore, it modulates GFR in a differentiated mode, depending on the concentration used. The GFR increase at 250 pmol/l ET-3 seems to be mediated by endothelium-derived nitric oxide. In addition to its glomerular action, ET-3 might also affect tubular sodium transport.", "contents": "Endothelin-3 modulates glomerular filtration rate in the isolated perfused rat kidney. The present study has been performed to evaluate hemodynamic and tubular effects of various endothelin-3 (ET-3) concentrations on the isolated perfused rat kidney. Using this experimental system we observed a profound reduction of renal perfusate flow at all ET-3 concentrations tested (50, 250 and 500 pmol/l), suggesting that the vasoconstrictive potency of ET-3 in the kidney is comparable to that described for endothelin-1 (ET-1). The effects on glomerular filtration rate (GFR) differed depending on the ET-3 dose applied. While 250 pmol/l ET-3 increased GFR by 30%, 500 pmol/l ET-3 markedly reduced GFR. 50 pmol/l ET-3 did not alter GFR although renal vascular resistance significantly increased. Infusion of 1 mumol/l N-nitro-L-arginine, a specific and potent inhibitor of nitric oxide synthesis in endothelial cells, abolished the GFR elevation induced by 250 pmol/l ET-3. In parallel with the changes of GFR we observed an increase in sodium reabsorption at 250 pmol/l and a decrease of this parameter at 500 pmol/l ET-3. Moreover, an ET-3 concentration (500 pmol/l), which induced a dramatic fall in tubular sodium load, led to an increase of fractional sodium excretion and to a decrease of renal oxygen consumption. We conclude that ET-3 is a potent vasoconstrictor in the isolated perfused rat kidney. Furthermore, it modulates GFR in a differentiated mode, depending on the concentration used. The GFR increase at 250 pmol/l ET-3 seems to be mediated by endothelium-derived nitric oxide. In addition to its glomerular action, ET-3 might also affect tubular sodium transport."} {"id": "PMID:1282729", "title": "Influence of colloidal bismuth subcitrate on enzyme secretion from isolated rat pancreatic acinar cells.", "content": "Bismuth salts are currently used as monotherapy or in combination with antibiotics for the treatment of Helicobacter pylori-associated peptic ulcer disease. Besides encouraging clinical results with colloidal bismuth subcitrate (CBS), there is an ongoing fear of organ toxicity with the use of bismuth salts. To study potential toxic effects of CBS under short-term exposure, we tested the influence of CBS on amylase secretion from isolated rat pancreatic acinar cells under basal conditions and following carbachol (CCh) and ceruletide (CRT) stimulation. Basal secretion was reduced by 8.9 +/- 9.6% (n = 10) (mean +/- SEM) (P < 0.05), 5.2 +/- 9.2% (P < 0.05), 9.4 +/- 6.4% (P < 0.01), and 6.2 +/- 12.2% (P < 0.05) with 0.001, 0.01, 0.1, and 1 micrograms/ml CBS, respectively. With 10 micrograms/ml and 100 micrograms/ml CBS, basal amylase secretion was increased in a dose-dependent manner, by 13.7 +/- 11.7% (P < 0.05) and 24.5 +/- 12.8% (P < 0.01). CCh (10(-5) M)- and CRT (3 x 10(-10) M)-stimulated secretory responses were not altered significantly by any of the CBS doses used. In concentrations above 1 microgram/ml, CBS increased pancreatic amylase secretion. Amylase secretion in response to secretagogues was not affected by CBS. These findings are unlikely to be associated with a toxic effect of CBS on exocrine pancreatic acinar cell function.", "contents": "Influence of colloidal bismuth subcitrate on enzyme secretion from isolated rat pancreatic acinar cells. Bismuth salts are currently used as monotherapy or in combination with antibiotics for the treatment of Helicobacter pylori-associated peptic ulcer disease. Besides encouraging clinical results with colloidal bismuth subcitrate (CBS), there is an ongoing fear of organ toxicity with the use of bismuth salts. To study potential toxic effects of CBS under short-term exposure, we tested the influence of CBS on amylase secretion from isolated rat pancreatic acinar cells under basal conditions and following carbachol (CCh) and ceruletide (CRT) stimulation. Basal secretion was reduced by 8.9 +/- 9.6% (n = 10) (mean +/- SEM) (P < 0.05), 5.2 +/- 9.2% (P < 0.05), 9.4 +/- 6.4% (P < 0.01), and 6.2 +/- 12.2% (P < 0.05) with 0.001, 0.01, 0.1, and 1 micrograms/ml CBS, respectively. With 10 micrograms/ml and 100 micrograms/ml CBS, basal amylase secretion was increased in a dose-dependent manner, by 13.7 +/- 11.7% (P < 0.05) and 24.5 +/- 12.8% (P < 0.01). CCh (10(-5) M)- and CRT (3 x 10(-10) M)-stimulated secretory responses were not altered significantly by any of the CBS doses used. In concentrations above 1 microgram/ml, CBS increased pancreatic amylase secretion. Amylase secretion in response to secretagogues was not affected by CBS. These findings are unlikely to be associated with a toxic effect of CBS on exocrine pancreatic acinar cell function."} {"id": "PMID:1282727", "title": "Acute lowering of plasma oncotic pressure increases filtration fraction and sodium excretion in conscious sheep.", "content": "We examined the effect of acutely lowering the colloid osmotic pressure by removing plasma (36.2 +/- 3.1 ml/kg) and replacing it with Hartmann's solution (93.0 +/- 8.2 ml/kg) in 6 conscious merino sheep. The colloid osmotic pressure was reduced significantly (p < 0.05) from 20.3 +/- 0.9 to 8.5 +/- 2.5 mm Hg 0 h after plasmapheresis and to 15.2 +/- 0.8 mm Hg 20 h after treatment. The filtration fraction increased from 0.16 +/- 0.02 to 0.27 +/- 0.02 at 0 h (p < 0.05 vs. control) and to 0.20 +/- 0.02 at 20 h after treatment (p < 0.05 vs. control). At 0 h after plasmapheresis, there was an increase in both sodium excretion from 187 +/- 69 to 459 +/- 82 mumol.min-1 (p < 0.05) and in fractional sodium excretion from 1.6 +/- 0.4 to 4.4 +/- 1.0% (p < 0.05). The results are consistent with the hypothesis that acute alteration of Starling forces produce clinically significant effects on both glomerular filtration and tubular reabsorption.", "contents": "Acute lowering of plasma oncotic pressure increases filtration fraction and sodium excretion in conscious sheep. We examined the effect of acutely lowering the colloid osmotic pressure by removing plasma (36.2 +/- 3.1 ml/kg) and replacing it with Hartmann's solution (93.0 +/- 8.2 ml/kg) in 6 conscious merino sheep. The colloid osmotic pressure was reduced significantly (p < 0.05) from 20.3 +/- 0.9 to 8.5 +/- 2.5 mm Hg 0 h after plasmapheresis and to 15.2 +/- 0.8 mm Hg 20 h after treatment. The filtration fraction increased from 0.16 +/- 0.02 to 0.27 +/- 0.02 at 0 h (p < 0.05 vs. control) and to 0.20 +/- 0.02 at 20 h after treatment (p < 0.05 vs. control). At 0 h after plasmapheresis, there was an increase in both sodium excretion from 187 +/- 69 to 459 +/- 82 mumol.min-1 (p < 0.05) and in fractional sodium excretion from 1.6 +/- 0.4 to 4.4 +/- 1.0% (p < 0.05). The results are consistent with the hypothesis that acute alteration of Starling forces produce clinically significant effects on both glomerular filtration and tubular reabsorption."} {"id": "PMID:1282730", "title": "In vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient.", "content": "We have recently isolated an apparently novel retrovirus (LM7) from a patient with multiple sclerosis (MS). We present here results showing that (1) LM7 retrovirus can be transmitted in vitro to a normal human leptomeningeal cell culture and that (2) specific antibody against this retroviral strain can be detected in MS cases. Our results suggest that, if this virus is an endogenous retrovirus, it is different from human endogenous elements already described.", "contents": "In vitro transmission and antigenicity of a retrovirus isolated from a multiple sclerosis patient. We have recently isolated an apparently novel retrovirus (LM7) from a patient with multiple sclerosis (MS). We present here results showing that (1) LM7 retrovirus can be transmitted in vitro to a normal human leptomeningeal cell culture and that (2) specific antibody against this retroviral strain can be detected in MS cases. Our results suggest that, if this virus is an endogenous retrovirus, it is different from human endogenous elements already described."} {"id": "PMID:1282734", "title": "[Benign prostatic hyperplasia--alternative (nonsurgical) possibilities of therapy].", "content": "The authors summarize contemporary possibilities of alternative treatment of benign hyperplasia of the prostate which could at least partially replace surgery. The authors present also the results of the first clinical investigations using different procedures. The list comprises also experience assembled in Czechoslovak departments.", "contents": "[Benign prostatic hyperplasia--alternative (nonsurgical) possibilities of therapy]. The authors summarize contemporary possibilities of alternative treatment of benign hyperplasia of the prostate which could at least partially replace surgery. The authors present also the results of the first clinical investigations using different procedures. The list comprises also experience assembled in Czechoslovak departments."} {"id": "PMID:1282742", "title": "Invertebrate GABA and glutamate receptors: molecular biology reveals predictable structures but some unusual pharmacologies.", "content": "Determination of the sequences of invertebrate gamma-aminobutyric acid (GABA)-gated and glutamate-gated receptor/ion channels, through the application of recombinant DNA methods, is not just an academic exercise to effect evolutionary comparisons with the sequences of the corresponding vertebrate receptors. The isolation of DNA clones would provide the tools to investigate the exact locations and functional properties of these neurotransmitter receptors within simple nervous systems. In addition, since GABA receptors, at least, have been suggested to be the targets of certain pesticides, the availability of invertebrate receptor cDNAs might provide the agrochemical industry with the basis for 'high-throughput' screening methods for novel pesticidal compounds. Recently, the isolation of molluscan and Drosophila GABA receptor and glutamate receptor cDNAs, and the pharmacological properties of a GABA receptor expressed from one of these clones, have been reported. These studies should stimulate further research into the electrophysiology and pharmacology of native invertebrate ion channel proteins.", "contents": "Invertebrate GABA and glutamate receptors: molecular biology reveals predictable structures but some unusual pharmacologies. Determination of the sequences of invertebrate gamma-aminobutyric acid (GABA)-gated and glutamate-gated receptor/ion channels, through the application of recombinant DNA methods, is not just an academic exercise to effect evolutionary comparisons with the sequences of the corresponding vertebrate receptors. The isolation of DNA clones would provide the tools to investigate the exact locations and functional properties of these neurotransmitter receptors within simple nervous systems. In addition, since GABA receptors, at least, have been suggested to be the targets of certain pesticides, the availability of invertebrate receptor cDNAs might provide the agrochemical industry with the basis for 'high-throughput' screening methods for novel pesticidal compounds. Recently, the isolation of molluscan and Drosophila GABA receptor and glutamate receptor cDNAs, and the pharmacological properties of a GABA receptor expressed from one of these clones, have been reported. These studies should stimulate further research into the electrophysiology and pharmacology of native invertebrate ion channel proteins."} {"id": "PMID:1282743", "title": "Characteristics of function-specific pathways in the sympathetic nervous system.", "content": "The autonomic nervous system enables all of our body systems to operate in an external environment that is both physically and emotionally challenging. Despite voluntary and involuntary interventions, the composition of the internal environment is maintained. Autonomic dysfunction, particularly in aging people, reveals the importance of this efferent neural control for the wellbeing of our bodies and minds. Although the sympathetic component of this system has been widely thought to be concerned only with the body's response to stress, we discuss here how a range of neuroscientific techniques has started to reveal the specialized properties of functional pathways in the sympathetic system at molecular, cellular and integrative levels. The diversity observed is not compatible with a simple neuroendocrine role of this system.", "contents": "Characteristics of function-specific pathways in the sympathetic nervous system. The autonomic nervous system enables all of our body systems to operate in an external environment that is both physically and emotionally challenging. Despite voluntary and involuntary interventions, the composition of the internal environment is maintained. Autonomic dysfunction, particularly in aging people, reveals the importance of this efferent neural control for the wellbeing of our bodies and minds. Although the sympathetic component of this system has been widely thought to be concerned only with the body's response to stress, we discuss here how a range of neuroscientific techniques has started to reveal the specialized properties of functional pathways in the sympathetic system at molecular, cellular and integrative levels. The diversity observed is not compatible with a simple neuroendocrine role of this system."} {"id": "PMID:1282748", "title": "Secreted acetylcholinesterase: non-classical aspects of a classical enzyme.", "content": "Recent evidence suggests that termination of cholinergic transmission is just one of the many ways in which acetylcholinesterase (AChE) could influence neuronal function. Neuronal AChE can be secreted from several brain regions, while purified AChE possesses several properties (in addition to its cholinesterase activity) that can affect neuronal function, including the abilities to influence certain membrane conductances, enhance excitatory amino acid transmission and hydrolyse peptides. Loss of AChE and its non-classical actions would have a profound effect on brain function in neurodegenerative diseases such as Alzheimer's disease where there is widespread loss of AChE-containing neurons.", "contents": "Secreted acetylcholinesterase: non-classical aspects of a classical enzyme. Recent evidence suggests that termination of cholinergic transmission is just one of the many ways in which acetylcholinesterase (AChE) could influence neuronal function. Neuronal AChE can be secreted from several brain regions, while purified AChE possesses several properties (in addition to its cholinesterase activity) that can affect neuronal function, including the abilities to influence certain membrane conductances, enhance excitatory amino acid transmission and hydrolyse peptides. Loss of AChE and its non-classical actions would have a profound effect on brain function in neurodegenerative diseases such as Alzheimer's disease where there is widespread loss of AChE-containing neurons."} {"id": "PMID:1282749", "title": "Neurochemical-neuroendocrine systems in the brain controlling macronutrient intake and metabolism.", "content": "Appetite, energy balance and body weight gain are modulated by diverse neurochemical and neuroendocrine signals from different organs in the body and diverse regions in the brain. The hypothalamus plays an important integrative function in this process, acting through a variety of systems that involve a close interaction between nutrients, amines, neuropeptides and hormones. These systems underlie normal nutrient intake and metabolism and are thought to be responsible for shifts in feeding behavior across the circadian cycle and fluctuations relating to gender and age in both rats and humans. Moreover, alterations in these normal neurochemical-neuroendocrine systems may be associated with abnormal eating patterns, such as anorexia nervosa, bulimia and obesity. Understanding the systems that control eating behavior might provide a foundation for the treatment and possible prevention of such disorders.", "contents": "Neurochemical-neuroendocrine systems in the brain controlling macronutrient intake and metabolism. Appetite, energy balance and body weight gain are modulated by diverse neurochemical and neuroendocrine signals from different organs in the body and diverse regions in the brain. The hypothalamus plays an important integrative function in this process, acting through a variety of systems that involve a close interaction between nutrients, amines, neuropeptides and hormones. These systems underlie normal nutrient intake and metabolism and are thought to be responsible for shifts in feeding behavior across the circadian cycle and fluctuations relating to gender and age in both rats and humans. Moreover, alterations in these normal neurochemical-neuroendocrine systems may be associated with abnormal eating patterns, such as anorexia nervosa, bulimia and obesity. Understanding the systems that control eating behavior might provide a foundation for the treatment and possible prevention of such disorders."} {"id": "PMID:1282750", "title": "Itching for an explanation.", "content": "Itch is a distinct sensation arising from the superficial layers of skin and mucous membranes. It is elicited by histamine and probably other endogenous chemicals that excite subpopulations of unmyelinated primary afferents and spinal neurones projecting through the anterolateral quadrant to the brain. The two popular views, which propose either that itch is signalled by a labelled line system of peripheral and central itch-specific neurones or that itch is the subliminal form of pain, both fail to explain convincingly many known features. Alternative theories emphasize central processes that extract the relevant information from afferents with broad sensitivity spectra for pruritogenic and noxious stimuli. Thus, itch presents an irritating challenge for the specificity theory of somatosensation.", "contents": "Itching for an explanation. Itch is a distinct sensation arising from the superficial layers of skin and mucous membranes. It is elicited by histamine and probably other endogenous chemicals that excite subpopulations of unmyelinated primary afferents and spinal neurones projecting through the anterolateral quadrant to the brain. The two popular views, which propose either that itch is signalled by a labelled line system of peripheral and central itch-specific neurones or that itch is the subliminal form of pain, both fail to explain convincingly many known features. Alternative theories emphasize central processes that extract the relevant information from afferents with broad sensitivity spectra for pruritogenic and noxious stimuli. Thus, itch presents an irritating challenge for the specificity theory of somatosensation."} {"id": "PMID:1282751", "title": "Suppression of programmed neuronal death by sustained elevation of cytoplasmic calcium.", "content": "Chronic depolarization greatly increases the survival of many types of neurons in culture. In at least some cases this enhancement of survival consists of the suppression of programmed cell death, a type of death occurring in developing neurons deprived of sufficient neurotrophic factor support. Available evidence suggests that the effect of depolarization on survival is mediated by a sustained rise of cytoplasmic free Ca2+, apparently caused by influx of Ca2+ through voltage-gated channels. This review discusses what is known about the mechanism by which prolonged depolarization and increased intracellular Ca2+ promote survival.", "contents": "Suppression of programmed neuronal death by sustained elevation of cytoplasmic calcium. Chronic depolarization greatly increases the survival of many types of neurons in culture. In at least some cases this enhancement of survival consists of the suppression of programmed cell death, a type of death occurring in developing neurons deprived of sufficient neurotrophic factor support. Available evidence suggests that the effect of depolarization on survival is mediated by a sustained rise of cytoplasmic free Ca2+, apparently caused by influx of Ca2+ through voltage-gated channels. This review discusses what is known about the mechanism by which prolonged depolarization and increased intracellular Ca2+ promote survival."} {"id": "PMID:1282752", "title": "Molecular messengers of olfaction.", "content": "Our knowledge of olfactory signal transduction has been greatly clarified by several recent advances. Molecular cloning has revealed a large family of putative odorant receptors localized to olfactory epithelium that display a seven-transmembrane-domain motif suggesting an association with G proteins. Very potent and rapid enhancement of both adenylyl cyclase and phosphoinositide turnover has been demonstrated in response to odorants both in isolated olfactory cilia and primary olfactory receptor neuronal cultures. A Ca(2+)-calmodulin-dependent phosphodiesterase has been localized to olfactory cilia. A key role for Ca2+ is evident from many investigations. More recently, odorants have also been shown to affect the levels of cGMP in olfactory receptor neurons. The involvement of multiple second messengers may provide mechanisms for both fine-tuning and desensitization of olfaction.", "contents": "Molecular messengers of olfaction. Our knowledge of olfactory signal transduction has been greatly clarified by several recent advances. Molecular cloning has revealed a large family of putative odorant receptors localized to olfactory epithelium that display a seven-transmembrane-domain motif suggesting an association with G proteins. Very potent and rapid enhancement of both adenylyl cyclase and phosphoinositide turnover has been demonstrated in response to odorants both in isolated olfactory cilia and primary olfactory receptor neuronal cultures. A Ca(2+)-calmodulin-dependent phosphodiesterase has been localized to olfactory cilia. A key role for Ca2+ is evident from many investigations. More recently, odorants have also been shown to affect the levels of cGMP in olfactory receptor neurons. The involvement of multiple second messengers may provide mechanisms for both fine-tuning and desensitization of olfaction."} {"id": "PMID:1282753", "title": "[Effect of kontrikal on the course of experimental nonspecific phacogenic uveitis].", "content": "Nonspecific phacogenic uveitis (NPGU) was simulated in 21 chinchilla rabbits to follow the time course of the blood serum proteolytic activity and the principal protease inhibitors (alpha 1 inhibitor and alpha 2 macroglobulin) in various stages of the inflammatory process. Effects of contrykal, a synthetic protease inhibitor, on these parameters and the course of the inflammation was also under study. The results evidence that i.v. and subconjunctival contrykal administration reduced the periods of NPGU treatment 1.5-2 times.", "contents": "[Effect of kontrikal on the course of experimental nonspecific phacogenic uveitis]. Nonspecific phacogenic uveitis (NPGU) was simulated in 21 chinchilla rabbits to follow the time course of the blood serum proteolytic activity and the principal protease inhibitors (alpha 1 inhibitor and alpha 2 macroglobulin) in various stages of the inflammatory process. Effects of contrykal, a synthetic protease inhibitor, on these parameters and the course of the inflammation was also under study. The results evidence that i.v. and subconjunctival contrykal administration reduced the periods of NPGU treatment 1.5-2 times."} {"id": "PMID:1282755", "title": "A preliminary map of epitopes on envelope glycoprotein E1 of HCV strain Brescia.", "content": "Monoclonal antibodies (MAbs) directed against envelope glycoprotein E1 (gp51-54) of hog cholera virus (HCV) strain Brescia have been shown to recognize four different antigenic domains A, B, C and D. Epitopes of within domain A have mainly been found conserved among HCV strains, whereas epitopes within domains B, C and D are not conserved. We used transiently expressed hybrid E1 genes of HCV strains Brescia and \"C\" to map the non-conserved epitopes on E1. Epitopes in domains B and C are located within the ultimate N-terminal 104 amino acids. The non-conserved subdomain A3 is most probably located between domains B/C and a hydrophobic region, which is highly conserved between HCV strains Brescia and \"C\". The conserved subdomains A1 and A2 are probably located in the vicinity and C-terminally of this conserved, hydrophobic region, which is near the centre of the E1 amino acid sequence.", "contents": "A preliminary map of epitopes on envelope glycoprotein E1 of HCV strain Brescia. Monoclonal antibodies (MAbs) directed against envelope glycoprotein E1 (gp51-54) of hog cholera virus (HCV) strain Brescia have been shown to recognize four different antigenic domains A, B, C and D. Epitopes of within domain A have mainly been found conserved among HCV strains, whereas epitopes within domains B, C and D are not conserved. We used transiently expressed hybrid E1 genes of HCV strains Brescia and \"C\" to map the non-conserved epitopes on E1. Epitopes in domains B and C are located within the ultimate N-terminal 104 amino acids. The non-conserved subdomain A3 is most probably located between domains B/C and a hydrophobic region, which is highly conserved between HCV strains Brescia and \"C\". The conserved subdomains A1 and A2 are probably located in the vicinity and C-terminally of this conserved, hydrophobic region, which is near the centre of the E1 amino acid sequence."} {"id": "PMID:1282754", "title": "[Pathogenetic therapy of spontaneous corneal perforation after extracapsular cataract extraction].", "content": "The author presents a case with spontaneous perforation of the cornea after extracapsular cataract extraction in a female patient with rheumatoid arthritis. Systemic disorganization of the connective tissue and elevated collagenase activity essentially contribute to the pathogenesis of corneal perforation. Therefore, besides antibacterial drugs, collagenase inhibitors, 3% aqueous solution of cysteine, antimeasles gamma-globulin, and a regeneration stimulant, 5% ascorbic acid aqueous solution, were used in the treatment. The pathogenetic therapy was conducive to early healing of the corneal defect and helped save the eye and preserve its good function (0.8 s + 10.0 diopters).", "contents": "[Pathogenetic therapy of spontaneous corneal perforation after extracapsular cataract extraction]. The author presents a case with spontaneous perforation of the cornea after extracapsular cataract extraction in a female patient with rheumatoid arthritis. Systemic disorganization of the connective tissue and elevated collagenase activity essentially contribute to the pathogenesis of corneal perforation. Therefore, besides antibacterial drugs, collagenase inhibitors, 3% aqueous solution of cysteine, antimeasles gamma-globulin, and a regeneration stimulant, 5% ascorbic acid aqueous solution, were used in the treatment. The pathogenetic therapy was conducive to early healing of the corneal defect and helped save the eye and preserve its good function (0.8 s + 10.0 diopters)."} {"id": "PMID:1282756", "title": "Antigen selection and presentation to protect against transmissible gastroenteritis coronavirus.", "content": "The antigenic structure of the S glycoprotein of transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) has been determined and correlated with the physical structure. Four antigenic sites have been defined (A, B, C, and D). The sites involved in the neutralization of TGEV are: A, D, and B, sites A and D being antigenically dominant for TGEV neutralization in vitro. These two sites have specific properties of interest: site A is highly conserved and is present in coronaviruses of three animal species, and site D can be represented by synthetic peptides. Both sites might be relevant in protection in vivo. PRCV does not have sites B and C, due to a genomic deletion. Complex antigenic sites, i.e., conformation and glycosylation dependent sites, have been represented by simple mimotopes selected from a library expressing recombinant peptides with random sequences, or by anti-idiotypic internal image monoclonal antibodies. An epidemiological tree relating the TGEVs and PRCVs has been proposed. The estimated mutation fixation rate of 7 +/- 2 x 10(-4) substitutions per nucleotide and year indicates that TGEV related coronaviruses show similar variability to other RNA viruses. In order to induce secretory immunity, different segments of the S gene have been expressed using a virulent forms of Salmonella typhimurium and adenovirus. These vectors, with a tropism for Peyer's patches may be ideal candidates in protection against TGEV.", "contents": "Antigen selection and presentation to protect against transmissible gastroenteritis coronavirus. The antigenic structure of the S glycoprotein of transmissible gastroenteritis virus (TGEV) and porcine respiratory coronavirus (PRCV) has been determined and correlated with the physical structure. Four antigenic sites have been defined (A, B, C, and D). The sites involved in the neutralization of TGEV are: A, D, and B, sites A and D being antigenically dominant for TGEV neutralization in vitro. These two sites have specific properties of interest: site A is highly conserved and is present in coronaviruses of three animal species, and site D can be represented by synthetic peptides. Both sites might be relevant in protection in vivo. PRCV does not have sites B and C, due to a genomic deletion. Complex antigenic sites, i.e., conformation and glycosylation dependent sites, have been represented by simple mimotopes selected from a library expressing recombinant peptides with random sequences, or by anti-idiotypic internal image monoclonal antibodies. An epidemiological tree relating the TGEVs and PRCVs has been proposed. The estimated mutation fixation rate of 7 +/- 2 x 10(-4) substitutions per nucleotide and year indicates that TGEV related coronaviruses show similar variability to other RNA viruses. In order to induce secretory immunity, different segments of the S gene have been expressed using a virulent forms of Salmonella typhimurium and adenovirus. These vectors, with a tropism for Peyer's patches may be ideal candidates in protection against TGEV."} {"id": "PMID:1282757", "title": "Haemorrhagic disease of lagomorphs: evidence for a calicivirus.", "content": "Studies on the aetiological agents of rabbit haemorrhagic disease (RHD) and European brown hare syndrome show that the viruses responsible for these infections can be placed in the family Caliciviridae. Established members of this group are vesicular exanthema virus (prototype), San Miguel sea lion virus and feline calcivirus. The human hepatitis E virus and the Norwalk agent may soon be included. The RHD virus genome consists of a positive stranded RNA molecule composed of 7437 nucleotides. A major subgenomic RNA of 2.2 kb, colinear with the 3' end of the genomic RNA, can also be recovered from infected liver tissue, and both RNAs are enclosed within viral capsids formed by a single major protein of approximately 60 kDa. Electron microscopic examination of organ suspensions from diseased animals shows two types of particle; 35-40 nm complete virions have the regularly arranged cup-shaped depressions typical of calcivirus morphology, and 23-25 nm smooth particles resulting from degradation of the outer surface structures of the complete virions.", "contents": "Haemorrhagic disease of lagomorphs: evidence for a calicivirus. Studies on the aetiological agents of rabbit haemorrhagic disease (RHD) and European brown hare syndrome show that the viruses responsible for these infections can be placed in the family Caliciviridae. Established members of this group are vesicular exanthema virus (prototype), San Miguel sea lion virus and feline calcivirus. The human hepatitis E virus and the Norwalk agent may soon be included. The RHD virus genome consists of a positive stranded RNA molecule composed of 7437 nucleotides. A major subgenomic RNA of 2.2 kb, colinear with the 3' end of the genomic RNA, can also be recovered from infected liver tissue, and both RNAs are enclosed within viral capsids formed by a single major protein of approximately 60 kDa. Electron microscopic examination of organ suspensions from diseased animals shows two types of particle; 35-40 nm complete virions have the regularly arranged cup-shaped depressions typical of calcivirus morphology, and 23-25 nm smooth particles resulting from degradation of the outer surface structures of the complete virions."} {"id": "PMID:1282760", "title": "[Conditions for dextranase formation by Paecilomyces lilacinus].", "content": "Induced formation conditions of dextranase by Paecilomyces lilacinus were investigated. Effect of various carbohydrates on dextranase formation was examined, dextran was the best C-source and as an inducer. The effect of dextran with different molecular weight (from 17.2 to 1000 kD) on dextranase formation was compared, productivity of dextranase increased with increase of dextran molecular weight. When dextran of 1000 kD was used as C-source. The enzyme formation was 40% higher than that 17.2 kD dextran. When other sugars were separately added to the medium with dextran, the enzyme formation was repressed. Besides C-source, the other optimum conditions of dextranase formation were as follows: N-source, beef peptone; medium initial pH, 6.0-7.0; culture temperature, 28 degrees C; inoculum amount about 10%, and the organism was cultivated for 6 days on 200 r/min shaker in 250 ml flasker with 50 ml medium.", "contents": "[Conditions for dextranase formation by Paecilomyces lilacinus]. Induced formation conditions of dextranase by Paecilomyces lilacinus were investigated. Effect of various carbohydrates on dextranase formation was examined, dextran was the best C-source and as an inducer. The effect of dextran with different molecular weight (from 17.2 to 1000 kD) on dextranase formation was compared, productivity of dextranase increased with increase of dextran molecular weight. When dextran of 1000 kD was used as C-source. The enzyme formation was 40% higher than that 17.2 kD dextran. When other sugars were separately added to the medium with dextran, the enzyme formation was repressed. Besides C-source, the other optimum conditions of dextranase formation were as follows: N-source, beef peptone; medium initial pH, 6.0-7.0; culture temperature, 28 degrees C; inoculum amount about 10%, and the organism was cultivated for 6 days on 200 r/min shaker in 250 ml flasker with 50 ml medium."} {"id": "PMID:1282762", "title": "[A unique marker of Pseudomonas from the first group of rRNA homology--selective sensitivity to the bacteriostatic action of barium ions].", "content": "On the basis of the study of the bacteriostatic action of chlorides and nitrates of barium and 24 other metals on 18 Pseudomonas species of all groups of rRNA homology and on 49 bacterial species belonging to 25 other genera, unique selective sensitivity to the bacteriostatic action of Ba2+ ions has been established in Pseudomonas of the first group of rRNA homology. The marker of barium sensitivity is in line with changes in the classification of Pseudomonas and is of interest for their further more precise systematization. The test for barium sensitivity of bacteria helps simplify the identification of Pseudomonas of the first group of rRNA homology and makes the identification more accurate.", "contents": "[A unique marker of Pseudomonas from the first group of rRNA homology--selective sensitivity to the bacteriostatic action of barium ions]. On the basis of the study of the bacteriostatic action of chlorides and nitrates of barium and 24 other metals on 18 Pseudomonas species of all groups of rRNA homology and on 49 bacterial species belonging to 25 other genera, unique selective sensitivity to the bacteriostatic action of Ba2+ ions has been established in Pseudomonas of the first group of rRNA homology. The marker of barium sensitivity is in line with changes in the classification of Pseudomonas and is of interest for their further more precise systematization. The test for barium sensitivity of bacteria helps simplify the identification of Pseudomonas of the first group of rRNA homology and makes the identification more accurate."} {"id": "PMID:1282763", "title": "[The fractional composition of immunoglobulin preparations studied by gel filtration on different carriers and by high-pressure liquid chromatography].", "content": "The fractional composition of immunoglobulin preparations produced by different manufacturing enterprises of this country has been studied by gel chromatography in columns packed with different carriers (Sephadex G-200 and ultragel AcA-34) and by high-performance liquid chromatography (HPLC). This study has revealed the nonstandard character of immunoglobulin preparations produced according to the same technological procedure (modified Cohn's method). The fractionation of immunoglobulins on different carriers with the use of different methods has yielded similar results confirmed by the statistical processing of the data. The results obtained in the study of the fractional composition of immunoglobulin preparations evidence that gel filtration with the use of ultragel and HPLC have greater resolving capacity in comparison with the method of gel filtration on traditionally used Sephadex G-200.", "contents": "[The fractional composition of immunoglobulin preparations studied by gel filtration on different carriers and by high-pressure liquid chromatography]. The fractional composition of immunoglobulin preparations produced by different manufacturing enterprises of this country has been studied by gel chromatography in columns packed with different carriers (Sephadex G-200 and ultragel AcA-34) and by high-performance liquid chromatography (HPLC). This study has revealed the nonstandard character of immunoglobulin preparations produced according to the same technological procedure (modified Cohn's method). The fractionation of immunoglobulins on different carriers with the use of different methods has yielded similar results confirmed by the statistical processing of the data. The results obtained in the study of the fractional composition of immunoglobulin preparations evidence that gel filtration with the use of ultragel and HPLC have greater resolving capacity in comparison with the method of gel filtration on traditionally used Sephadex G-200."} {"id": "PMID:1282764", "title": "Evaluation of stroke rehabilitation by randomized controlled studies: a review.", "content": "In all, 22 reports of 20 randomized, controlled rehabilitation studies were evaluated. In 18 of these, the design of the trial was parallel, with a cross-over format being employed in the remaining 2 instances. Seven studies related to intensive rehabilitation during the early post-acute period. In six others, specific techniques--sometimes associated with traditional physiotherapy procedures--were compared: biofeedback, perceptual retraining, and amphetamine treatment. Eight experiments evaluated speech therapy in aphasia. Frequently, methodological considerations limited the interpretation of the results. The review showed that: 1) as regards activities of daily life and motor function, differences as between rehabilitation in stroke units on the one hand and non-rehabilitation or rehabilitation in medical wards on the other, were detected in relatively few quality studies and remained particularly inconclusive insofar as life in the home environment was concerned; 2) rehabilitation for aphasia and perceptual dysfunction proved effective for at least several months after acute stroke; 3) in general, examination of the reports cited revealed no differences in the effects of biofeedback and perceptual retraining vs conventional physiotherapy; 4) rehabilitation, whether administered by specialists or amateur caregivers purpose-trained by specialists, proved equally effective for aphasia. These conclusions constitute a valuable basis for the development and evaluation of modern rehabilitation programs for stroke patients.", "contents": "Evaluation of stroke rehabilitation by randomized controlled studies: a review. In all, 22 reports of 20 randomized, controlled rehabilitation studies were evaluated. In 18 of these, the design of the trial was parallel, with a cross-over format being employed in the remaining 2 instances. Seven studies related to intensive rehabilitation during the early post-acute period. In six others, specific techniques--sometimes associated with traditional physiotherapy procedures--were compared: biofeedback, perceptual retraining, and amphetamine treatment. Eight experiments evaluated speech therapy in aphasia. Frequently, methodological considerations limited the interpretation of the results. The review showed that: 1) as regards activities of daily life and motor function, differences as between rehabilitation in stroke units on the one hand and non-rehabilitation or rehabilitation in medical wards on the other, were detected in relatively few quality studies and remained particularly inconclusive insofar as life in the home environment was concerned; 2) rehabilitation for aphasia and perceptual dysfunction proved effective for at least several months after acute stroke; 3) in general, examination of the reports cited revealed no differences in the effects of biofeedback and perceptual retraining vs conventional physiotherapy; 4) rehabilitation, whether administered by specialists or amateur caregivers purpose-trained by specialists, proved equally effective for aphasia. These conclusions constitute a valuable basis for the development and evaluation of modern rehabilitation programs for stroke patients."} {"id": "PMID:1282765", "title": "Short-term restraint stress and s.c. saline injection alter the tissue levels of substance P and cholecystokinin in the peri-aqueductal grey and limbic regions of rat brain.", "content": "Rats were exposed to short-term restraint (held by the tail for 1 min), injected s.c. with saline or subjected to the combination of these treatments. Fifteen and 30 min after these treatments the means serum corticosterone level was significantly increased by more than four times, compared to rats taken directly from their home cages, indicating a stress response. In the peri-aqueductal grey, the level of substance P-like immunoreactivity was increased by 45% (P < 0.01) and 65% (P < 0.01) 30 and 60 min after the combined treatment, respectively. Significant increases of the level of substance P-like immunoreactivity in the peri-aqueductal grey were also found after restraint only and after a s.c. saline injection. Similar, but less marked, changes in the level of cholecystokinin-like immunoreactivity in the PAG were also seen. In the accumbens a significantly decreased level of substance P-like immunoreactivity was encountered at 15 and 30 min after treatment, while the levels of cholecystokinin- and neuropeptide Y-like immunoreactivity were not significantly changed. In other regions studied, no effects on peptide levels were seen. The changes in peptide levels had a time course similar to that of the increase in serum corticosterone. Also the successive removal of rats from a common cage was found to increase significantly the serum corticosterone and the substance P-like immunoreactivity in the peri-aqueductal grey in the animals that were taken late in sequence from the cage.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Short-term restraint stress and s.c. saline injection alter the tissue levels of substance P and cholecystokinin in the peri-aqueductal grey and limbic regions of rat brain. Rats were exposed to short-term restraint (held by the tail for 1 min), injected s.c. with saline or subjected to the combination of these treatments. Fifteen and 30 min after these treatments the means serum corticosterone level was significantly increased by more than four times, compared to rats taken directly from their home cages, indicating a stress response. In the peri-aqueductal grey, the level of substance P-like immunoreactivity was increased by 45% (P < 0.01) and 65% (P < 0.01) 30 and 60 min after the combined treatment, respectively. Significant increases of the level of substance P-like immunoreactivity in the peri-aqueductal grey were also found after restraint only and after a s.c. saline injection. Similar, but less marked, changes in the level of cholecystokinin-like immunoreactivity in the PAG were also seen. In the accumbens a significantly decreased level of substance P-like immunoreactivity was encountered at 15 and 30 min after treatment, while the levels of cholecystokinin- and neuropeptide Y-like immunoreactivity were not significantly changed. In other regions studied, no effects on peptide levels were seen. The changes in peptide levels had a time course similar to that of the increase in serum corticosterone. Also the successive removal of rats from a common cage was found to increase significantly the serum corticosterone and the substance P-like immunoreactivity in the peri-aqueductal grey in the animals that were taken late in sequence from the cage.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282766", "title": "[Whipple's disease].", "content": "The authors describe a case of Whipple's disease, characterized by arthralgias, chronic diarrhea and weight loss. The diagnosis was established on clinical, laboratorial and radiological grounds and confirmed histologically, through a duodenal biopsy. Rapid improvement occurred, soon after the beginning of antibiotic therapy.", "contents": "[Whipple's disease]. The authors describe a case of Whipple's disease, characterized by arthralgias, chronic diarrhea and weight loss. The diagnosis was established on clinical, laboratorial and radiological grounds and confirmed histologically, through a duodenal biopsy. Rapid improvement occurred, soon after the beginning of antibiotic therapy."} {"id": "PMID:1282767", "title": "An indirect method of measuring widths suitable for automated bone histomorphometry.", "content": "Orthogonal intercepts from random test lines (OIr), uniformly distributed intercepts (OIu), and areas and lengths (Ar/Le) were measured manually and by computer to determine individual profile and sample widths of artificial profiles and human osteoid seams. Individual widths were equal by Ar/Le and OIu methods. The means of individual profile widths (all methods), of all orthogonal intercepts (OIu and OIr), or of profile widths weighted in proportion to their lengths (Ar/Le) were also equal. Ar/Le and OIu had smaller variance than OIr. Discrepant individual OIu and Ar/Le widths in digitized images were corrected by thresholding and did not significantly affect sample means. Unweighted Ar/Le sample means were 15-44% lower than weighted means. Distributions of osteoid seam widths were not normal, and all but one had more than one mode. We conclude that the Ar/Le method is comparable to direct orthogonal intercept methods and suitable for automated histomorphometry.", "contents": "An indirect method of measuring widths suitable for automated bone histomorphometry. Orthogonal intercepts from random test lines (OIr), uniformly distributed intercepts (OIu), and areas and lengths (Ar/Le) were measured manually and by computer to determine individual profile and sample widths of artificial profiles and human osteoid seams. Individual widths were equal by Ar/Le and OIu methods. The means of individual profile widths (all methods), of all orthogonal intercepts (OIu and OIr), or of profile widths weighted in proportion to their lengths (Ar/Le) were also equal. Ar/Le and OIu had smaller variance than OIr. Discrepant individual OIu and Ar/Le widths in digitized images were corrected by thresholding and did not significantly affect sample means. Unweighted Ar/Le sample means were 15-44% lower than weighted means. Distributions of osteoid seam widths were not normal, and all but one had more than one mode. We conclude that the Ar/Le method is comparable to direct orthogonal intercept methods and suitable for automated histomorphometry."} {"id": "PMID:1282768", "title": "Glycerol injection to the rat trigeminal nerve: histological and immunohistochemical studies.", "content": "The effect of topical glycerol injection into the rat trigeminal nerves was investigated histologically and immunohistochemically. Anhydrous glycerol was injected into the preganglionic portion of the trigeminal nerves via a ventral approach. Extensive myelin swelling and axonolysis were observed in the rats killed 1 and 2 weeks after glycerol injection. Numerous inflammatory cells were seen especially in the animals sacrificed 1 week after surgery. Myelin disintegration continued up to 4 weeks after glycerol injection. In normal and saline injected sham operated nerves, calcitonin gene-related peptide (CGRP)- and substance P(SP)-like immunoreactivities were densely localized in the nerve fibers. A marked decrease in both CGRP- and SP-like immunofluorescence was seen in the nerves after glycerol injection. The remaining nerve fibers often had blunt endings with increased fluorescence. Swollen and winding structures were also found. These immunohistochemical changes were observed in the rats killed 1 and 2 weeks following surgery. A similar change but of lesser degree was seen in the 4-week-animal. The present study suggests that topical glycerol injection into the trigeminal nerve induces degeneration of the nerves immunoreactive to CGRP and SP. These changes emphasize the putative functional implications of the peptides in relieving the pain of trigeminal neuralgia after topical glycerol injection.", "contents": "Glycerol injection to the rat trigeminal nerve: histological and immunohistochemical studies. The effect of topical glycerol injection into the rat trigeminal nerves was investigated histologically and immunohistochemically. Anhydrous glycerol was injected into the preganglionic portion of the trigeminal nerves via a ventral approach. Extensive myelin swelling and axonolysis were observed in the rats killed 1 and 2 weeks after glycerol injection. Numerous inflammatory cells were seen especially in the animals sacrificed 1 week after surgery. Myelin disintegration continued up to 4 weeks after glycerol injection. In normal and saline injected sham operated nerves, calcitonin gene-related peptide (CGRP)- and substance P(SP)-like immunoreactivities were densely localized in the nerve fibers. A marked decrease in both CGRP- and SP-like immunofluorescence was seen in the nerves after glycerol injection. The remaining nerve fibers often had blunt endings with increased fluorescence. Swollen and winding structures were also found. These immunohistochemical changes were observed in the rats killed 1 and 2 weeks following surgery. A similar change but of lesser degree was seen in the 4-week-animal. The present study suggests that topical glycerol injection into the trigeminal nerve induces degeneration of the nerves immunoreactive to CGRP and SP. These changes emphasize the putative functional implications of the peptides in relieving the pain of trigeminal neuralgia after topical glycerol injection."} {"id": "PMID:1282769", "title": "Cerebrovascular effects of substance P after experimental subarachnoid haemorrhage.", "content": "The vasoactive effects of substance P (SP), as well as the content of cyclic guanine monophosphate (cGMP), were determined in the rabbit basilar artery after subarachnoid haemorrhage (SAH). Out of 47 rabbits, 24 were subjected to a SAH, induced by injecting 5 ml of autologous arterial blood into the cisterna magna; 23 were used as controls. In 20 animals (10 SAH and 10 controls), isometric tension recording of isolated rings of the basilar artery--dissected 2 days after SAH--was employed to assess the dose-dependent vasodilatation to SP (10(-10) to 10(-6) M) after precontraction with serotonin (10(-8) to 10(-5) M). In 15 animals (8 SAH and 7 controls), the basal cGMP content was measured in the basilar artery 2 days after SAH. In the other 12 animals (6 SAH and 6 controls), the increase in cGMP content was measured in the basilar artery after a 10-minute incubation with SP (10(-6) M). SP caused significantly less dilatation in animals subjected to SAH than in controls, especially for concentrations between 10(-9) and 10(-6) M (p < 0.001). The cGMP content in the arteries 2 days after SAH was significantly lower than in control arteries (31.5 +/- 7.3 against 57.3 +/- 4.3 pmoles/g tissue). In the preparations incubated with SP, the increase of cGMP was 440 +/- 115% in the control arteries, and only 97 +/- 30% in the arteries after SAH. It is concluded that the vasodilator activity of SP is significantly impaired after SAH.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Cerebrovascular effects of substance P after experimental subarachnoid haemorrhage. The vasoactive effects of substance P (SP), as well as the content of cyclic guanine monophosphate (cGMP), were determined in the rabbit basilar artery after subarachnoid haemorrhage (SAH). Out of 47 rabbits, 24 were subjected to a SAH, induced by injecting 5 ml of autologous arterial blood into the cisterna magna; 23 were used as controls. In 20 animals (10 SAH and 10 controls), isometric tension recording of isolated rings of the basilar artery--dissected 2 days after SAH--was employed to assess the dose-dependent vasodilatation to SP (10(-10) to 10(-6) M) after precontraction with serotonin (10(-8) to 10(-5) M). In 15 animals (8 SAH and 7 controls), the basal cGMP content was measured in the basilar artery 2 days after SAH. In the other 12 animals (6 SAH and 6 controls), the increase in cGMP content was measured in the basilar artery after a 10-minute incubation with SP (10(-6) M). SP caused significantly less dilatation in animals subjected to SAH than in controls, especially for concentrations between 10(-9) and 10(-6) M (p < 0.001). The cGMP content in the arteries 2 days after SAH was significantly lower than in control arteries (31.5 +/- 7.3 against 57.3 +/- 4.3 pmoles/g tissue). In the preparations incubated with SP, the increase of cGMP was 440 +/- 115% in the control arteries, and only 97 +/- 30% in the arteries after SAH. It is concluded that the vasodilator activity of SP is significantly impaired after SAH.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282770", "title": "[Intraarterial COMPA (cis-diammine-dichloroplatinum (II), vincristine, methotrexate, peplomycin, adriamycin) chemotherapy for bladder cancer].", "content": "Seventeen patients with bladder cancer were treated with semiselective intraarterial COMPA chemotherapy. One course of COMPA consisted of 20 mg/m2 cis-diammine-dichloroplatinum (CDDP) on days 4 and 5, 0.6 mg/m2 vincristine (VCR) (Oncovin) on days 1 and 2, 5 mg/m2 methotrexate (MTX) on days 2 and 3, 5 mg/body peplomycin (PEP) on days 1, 2 and 3, and 15 mg/m2 adriamycin (ADM) on day 4. These drugs were injected every 2 or 3 weeks through a polyurethane catheter the tip of which was placed just proximal to the aortic bifurcation and during injection both thighs were tied with a pressure of over 250 mmHg. From 2 to 6 courses (mean, 4.4 courses) were administered. Of the 17 patients, 4 achieved complete remission, 10 achieved partial remission and 3 showed no change. After this COMPA chemotherapy eight patients were able to retain their bladders while seven underwent immediate radical cystectomy. The adjuvant COMPA chemotherapy for two patients with pelvic metastasis after radical cystectomy showed good results. Mild degrees of anorexia, nausea, vomiting, hair loss, numbness of fingers and/or toes, leukopenia and intestinal paralysis were observed. Instrumental troubles were seen in two cases; one involved dislocation of the tip of the catheter, the other was infection of the reservoir. Intraarterial COMPA chemotherapy is effective for neoadjuvant therapy of invasive bladder cancer, bladder-preserving treatment and adjuvant therapy of pelvic metastasis.", "contents": "[Intraarterial COMPA (cis-diammine-dichloroplatinum (II), vincristine, methotrexate, peplomycin, adriamycin) chemotherapy for bladder cancer]. Seventeen patients with bladder cancer were treated with semiselective intraarterial COMPA chemotherapy. One course of COMPA consisted of 20 mg/m2 cis-diammine-dichloroplatinum (CDDP) on days 4 and 5, 0.6 mg/m2 vincristine (VCR) (Oncovin) on days 1 and 2, 5 mg/m2 methotrexate (MTX) on days 2 and 3, 5 mg/body peplomycin (PEP) on days 1, 2 and 3, and 15 mg/m2 adriamycin (ADM) on day 4. These drugs were injected every 2 or 3 weeks through a polyurethane catheter the tip of which was placed just proximal to the aortic bifurcation and during injection both thighs were tied with a pressure of over 250 mmHg. From 2 to 6 courses (mean, 4.4 courses) were administered. Of the 17 patients, 4 achieved complete remission, 10 achieved partial remission and 3 showed no change. After this COMPA chemotherapy eight patients were able to retain their bladders while seven underwent immediate radical cystectomy. The adjuvant COMPA chemotherapy for two patients with pelvic metastasis after radical cystectomy showed good results. Mild degrees of anorexia, nausea, vomiting, hair loss, numbness of fingers and/or toes, leukopenia and intestinal paralysis were observed. Instrumental troubles were seen in two cases; one involved dislocation of the tip of the catheter, the other was infection of the reservoir. Intraarterial COMPA chemotherapy is effective for neoadjuvant therapy of invasive bladder cancer, bladder-preserving treatment and adjuvant therapy of pelvic metastasis."} {"id": "PMID:1282771", "title": "[Transurethral resection of the prostate in the urological management for patients with stroke].", "content": "We discuss the transurethral resection of the prostate (TUR-P) on 40 patients in the chronic stage of stroke, all of whom were refractory to conservative managements of urinary disturbance. All patients, between 35 and 89 years old (mean: 52.6 years), had only one episode of stroke and were diagnosed as benign prostatic hypertrophy or bladder neck contracture that appeared to cause urinary disturbance in these patients. At six months after TUR-P, all except for one patient, who needed an indwelling catheter due to a reinfarction, were catheter free. Of these cases 36 (92%) obtained independent micturition and did not develop urinary incontinence except transiently postoperatively. Two cases with impaired mobility and one case with progressive senile dementia required helpmates and/or a commode and so forth postoperatively. It is concluded that in chronic stroke patients TUR-P is recommended for those with benign prostatic hypertrophy or bladder neck contracture.", "contents": "[Transurethral resection of the prostate in the urological management for patients with stroke]. We discuss the transurethral resection of the prostate (TUR-P) on 40 patients in the chronic stage of stroke, all of whom were refractory to conservative managements of urinary disturbance. All patients, between 35 and 89 years old (mean: 52.6 years), had only one episode of stroke and were diagnosed as benign prostatic hypertrophy or bladder neck contracture that appeared to cause urinary disturbance in these patients. At six months after TUR-P, all except for one patient, who needed an indwelling catheter due to a reinfarction, were catheter free. Of these cases 36 (92%) obtained independent micturition and did not develop urinary incontinence except transiently postoperatively. Two cases with impaired mobility and one case with progressive senile dementia required helpmates and/or a commode and so forth postoperatively. It is concluded that in chronic stroke patients TUR-P is recommended for those with benign prostatic hypertrophy or bladder neck contracture."} {"id": "PMID:1282772", "title": "[Value of prostate-specific antigen measurements with newly developed enzyme immunoassay (MARKIT-M PA)].", "content": "Serum prostate-specific antigen (PSA) levels in patients with prostate cancer and benign prostate hypertrophy (BPH) were investigated with a newly developed enzyme immunoassay (MARKIT-M PA, Dainippon Pharmaceutical Co. Ltd., Osaka, Japan). Sensitivity of the assay system is 0.5 ng/ml and the detection range is 0.5-100 ng/ml. There was a high linear correlation (r = 0.987) between the assay and MARKIT-F PA, and values obtained with the assay were almost equal to those yielded by MARKIT-F PA assay. Using the BPH group as a negative control, the upper cut-off value in BPH patients was determined to be 3.6 ng/ml. Of the 48 patients with untreated prostate cancer, 77% was detectable by means of MARKIT-M PA assay. Using the BPH group as a negative control, specificity and efficiency were 93% and 86%, respectively. In another group of 27 BPH patients whose blood samples were taken immediately after digital prostatic examination, PSA was elevated in 15%. During follow-up of prostate cancer patients, PSA was elevated in 82% at the time of clinically detectable progression. In 15 patients whose disease was clinically well controlled, all levels of PSA were observed to be negative. These findings suggests that detection of serum PSA with this assay is of great use both in the diagnosis and monitoring of prostate cancer patients.", "contents": "[Value of prostate-specific antigen measurements with newly developed enzyme immunoassay (MARKIT-M PA)]. Serum prostate-specific antigen (PSA) levels in patients with prostate cancer and benign prostate hypertrophy (BPH) were investigated with a newly developed enzyme immunoassay (MARKIT-M PA, Dainippon Pharmaceutical Co. Ltd., Osaka, Japan). Sensitivity of the assay system is 0.5 ng/ml and the detection range is 0.5-100 ng/ml. There was a high linear correlation (r = 0.987) between the assay and MARKIT-F PA, and values obtained with the assay were almost equal to those yielded by MARKIT-F PA assay. Using the BPH group as a negative control, the upper cut-off value in BPH patients was determined to be 3.6 ng/ml. Of the 48 patients with untreated prostate cancer, 77% was detectable by means of MARKIT-M PA assay. Using the BPH group as a negative control, specificity and efficiency were 93% and 86%, respectively. In another group of 27 BPH patients whose blood samples were taken immediately after digital prostatic examination, PSA was elevated in 15%. During follow-up of prostate cancer patients, PSA was elevated in 82% at the time of clinically detectable progression. In 15 patients whose disease was clinically well controlled, all levels of PSA were observed to be negative. These findings suggests that detection of serum PSA with this assay is of great use both in the diagnosis and monitoring of prostate cancer patients."} {"id": "PMID:1282773", "title": "[A study of bladder function in benign prostatic hyperplasia].", "content": "A study of bladder function was performed on 106 patients with benign prostatic hyperplasia (BPH), 21 of whom had cerebrovascular disease (CVD). The incidence of overactive bladder in 21 patients with CVD was 57% and was significantly higher than the 25% in 86 patients without CVD. The incidence of cases having residual urine of over 100 ml, was in the order of low compliance bladder, overactive bladder and normal bladder. The mean value of maximum voiding pressure in overactive bladder was higher than that in normal bladder. The high pressure was improved after the operation for BPH. Improvement of overactive bladder after the operation was seen in 9 of 13 patients without CVD while in 2 of 6 patients with CVD.", "contents": "[A study of bladder function in benign prostatic hyperplasia]. A study of bladder function was performed on 106 patients with benign prostatic hyperplasia (BPH), 21 of whom had cerebrovascular disease (CVD). The incidence of overactive bladder in 21 patients with CVD was 57% and was significantly higher than the 25% in 86 patients without CVD. The incidence of cases having residual urine of over 100 ml, was in the order of low compliance bladder, overactive bladder and normal bladder. The mean value of maximum voiding pressure in overactive bladder was higher than that in normal bladder. The high pressure was improved after the operation for BPH. Improvement of overactive bladder after the operation was seen in 9 of 13 patients without CVD while in 2 of 6 patients with CVD."} {"id": "PMID:1282774", "title": "[BEP (bleomycin, etoposide, cisplatin) therapy for testicular tumors].", "content": "We describe our experience with BEP (bleomycin, etoposide, cisplatin) therapy as chemotherapy for testicular tumors in 11 patients. Eight were non-seminomatous testicular cancer patients and 3 were seminoma patients. Three of 8 non-seminomatous testicular cancer patients had no evident metastasis and BEP therapy was performed for prophylaxis of recurrence. Other 5 non-seminomatous testicular cancer patients and 3 seminoma patients had metastatic lesions and BEP therapy was performed to cure these metastatic lesions. Ten of our 11 patients are living and disease-free. One non-seminomatous testicular cancer patient who had brain, lung, eye and bladder metastases and had an extremely elevated human chorionic gonadotropin (hCG) level responded only partially and died later due to disease progression. Side effects in most patients were nausea, vomiting, alopecia and leucopenia and all these side effects were reversible. Neuromuscular toxicity such as paresthesia or abdominal cramp that is sometimes encountered in PVB (cisplatin, vinblastine, bleomycin) therapy was not seen in our patients. Our results support the concept that BEP therapy is better than PVB therapy as an initial chemotherapy for testicular tumors.", "contents": "[BEP (bleomycin, etoposide, cisplatin) therapy for testicular tumors]. We describe our experience with BEP (bleomycin, etoposide, cisplatin) therapy as chemotherapy for testicular tumors in 11 patients. Eight were non-seminomatous testicular cancer patients and 3 were seminoma patients. Three of 8 non-seminomatous testicular cancer patients had no evident metastasis and BEP therapy was performed for prophylaxis of recurrence. Other 5 non-seminomatous testicular cancer patients and 3 seminoma patients had metastatic lesions and BEP therapy was performed to cure these metastatic lesions. Ten of our 11 patients are living and disease-free. One non-seminomatous testicular cancer patient who had brain, lung, eye and bladder metastases and had an extremely elevated human chorionic gonadotropin (hCG) level responded only partially and died later due to disease progression. Side effects in most patients were nausea, vomiting, alopecia and leucopenia and all these side effects were reversible. Neuromuscular toxicity such as paresthesia or abdominal cramp that is sometimes encountered in PVB (cisplatin, vinblastine, bleomycin) therapy was not seen in our patients. Our results support the concept that BEP therapy is better than PVB therapy as an initial chemotherapy for testicular tumors."} {"id": "PMID:1282775", "title": "[Successful management of choriocarcinoma of the testis with brain metastasis: a case report].", "content": "A 32-year-old Japanese male consulted a clinic complaining of gynecomastia. Right painless scrotal swelling was also detected. Right high orchiectomy was performed, then the surgical specimen was histopathologically confirmed as choriocarcinoma and mature teratoma. The imaging revealed cerebral, pulmonary, retroperitoneal metastases. After 3 courses of combination chemotherapy with cisplatin, etoposide and peplomycin (PEP therapy), the brain metastasis completely disappeared and the serum titer of the tumor markers such as beta-HCG became normal. The regression rates of lung and retroperitoneal metastases were 68% and 27%, respectively. Therefore, retroperitoneal lymph node dissection was performed. After the 5th course of PEP therapy, lung metastases disappeared completely. Until the present, no evidence of disease has persisted. The PEP therapy, which is a salvage therapy for refractory testicular cancer, was performed as first-line chemotherapy in this case. It was an excellent modality against choriocarcinoma, along with the surgical treatment.", "contents": "[Successful management of choriocarcinoma of the testis with brain metastasis: a case report]. A 32-year-old Japanese male consulted a clinic complaining of gynecomastia. Right painless scrotal swelling was also detected. Right high orchiectomy was performed, then the surgical specimen was histopathologically confirmed as choriocarcinoma and mature teratoma. The imaging revealed cerebral, pulmonary, retroperitoneal metastases. After 3 courses of combination chemotherapy with cisplatin, etoposide and peplomycin (PEP therapy), the brain metastasis completely disappeared and the serum titer of the tumor markers such as beta-HCG became normal. The regression rates of lung and retroperitoneal metastases were 68% and 27%, respectively. Therefore, retroperitoneal lymph node dissection was performed. After the 5th course of PEP therapy, lung metastases disappeared completely. Until the present, no evidence of disease has persisted. The PEP therapy, which is a salvage therapy for refractory testicular cancer, was performed as first-line chemotherapy in this case. It was an excellent modality against choriocarcinoma, along with the surgical treatment."} {"id": "PMID:1282776", "title": "Bacterially expressed core and envelope proteins of human immunodeficiency virus type-1 (HIV-1): comparative evaluation in detection of type-specific antibodies.", "content": "Recombinant proteins derived from immunodominant conserved domains of HIV-1 env and gag genes were synthesized in E. coli. An immunoblot system using total cell lysates was employed for the analysis of recombinant bacterial clones. Together 427 serum samples obtained from asymptomatic anti-HIV seropositive individuals, AIDS patients, healthy donors and persons suffering from various conditions were comparatively evaluated for the presence of HIV-1 antibodies using recombinant peptides and commercially available western blot (WB) and ELISA assays. The recombinant antigen product of plasmid pEX41 was found to be superior, with respect to sensitivity and specificity, to the viral gp41 which represents a diagnostically important constituent of the WB.", "contents": "Bacterially expressed core and envelope proteins of human immunodeficiency virus type-1 (HIV-1): comparative evaluation in detection of type-specific antibodies. Recombinant proteins derived from immunodominant conserved domains of HIV-1 env and gag genes were synthesized in E. coli. An immunoblot system using total cell lysates was employed for the analysis of recombinant bacterial clones. Together 427 serum samples obtained from asymptomatic anti-HIV seropositive individuals, AIDS patients, healthy donors and persons suffering from various conditions were comparatively evaluated for the presence of HIV-1 antibodies using recombinant peptides and commercially available western blot (WB) and ELISA assays. The recombinant antigen product of plasmid pEX41 was found to be superior, with respect to sensitivity and specificity, to the viral gp41 which represents a diagnostically important constituent of the WB."} {"id": "PMID:1282777", "title": "Identification of a cell membrane receptor for interferon induction by poly rI:rC.", "content": "PR-RK, a cell line derived from rabbit kidney cells (RK-13), was insensitive to the cytotoxic effect and interferon (IFN) inducing activity of the copolymer of riboinosinic and ribocytidylic acid (poly rI:rC). However, PR-RK was sensitive to the cytotoxic effect of the copolymer of riboadenylic and ribouridylic acid (poly rA:rU). Comparison of PR-RK cells and RK-13 cells by cytofluorometric analysis revealed that the binding of poly rI:rC was considerably reduced on PR-RK cells. These results suggested that the receptor for poly rI:rC might be different from the receptor for poly rA:rU, and this difference could provide a basis for the identification of the dsRNA receptor on cell surface. Western blot analysis of the components of cell membrane fraction prepared from RK-13 cells was performed by using a monoclonal antibody, which binds to cell membrane of RK-13 cells but not to PR-RK cells, and which blocks IFN induction by poly rI:rC in RK-13 cells. The 60K protein was identified as one of the poly rI:rC receptor protein.", "contents": "Identification of a cell membrane receptor for interferon induction by poly rI:rC. PR-RK, a cell line derived from rabbit kidney cells (RK-13), was insensitive to the cytotoxic effect and interferon (IFN) inducing activity of the copolymer of riboinosinic and ribocytidylic acid (poly rI:rC). However, PR-RK was sensitive to the cytotoxic effect of the copolymer of riboadenylic and ribouridylic acid (poly rA:rU). Comparison of PR-RK cells and RK-13 cells by cytofluorometric analysis revealed that the binding of poly rI:rC was considerably reduced on PR-RK cells. These results suggested that the receptor for poly rI:rC might be different from the receptor for poly rA:rU, and this difference could provide a basis for the identification of the dsRNA receptor on cell surface. Western blot analysis of the components of cell membrane fraction prepared from RK-13 cells was performed by using a monoclonal antibody, which binds to cell membrane of RK-13 cells but not to PR-RK cells, and which blocks IFN induction by poly rI:rC in RK-13 cells. The 60K protein was identified as one of the poly rI:rC receptor protein."} {"id": "PMID:1282778", "title": "Interferon-neutralizing or enhancing activities in hybridoma cell fluids after in vitro immunization.", "content": "Several hybridomas supernatants capable of interferon beta (IFN-beta) or \"IFN epsilon\" (\"IFN-eps\") neutralizing or enhancing activities were obtained after in vitro immunization of BALB/c and C57 mice spleen cells and their fusion with Sp2/0 plasmacytoma cells. Besides rather low anti-IFN-beta or \"eps\" antibody secretion several cloned hybridoma fluids contained a factor potentiating anti-viral activity of the both IFNs. It is speculated that this activity is due to production by some hybridomas of another lymphokine.", "contents": "Interferon-neutralizing or enhancing activities in hybridoma cell fluids after in vitro immunization. Several hybridomas supernatants capable of interferon beta (IFN-beta) or \"IFN epsilon\" (\"IFN-eps\") neutralizing or enhancing activities were obtained after in vitro immunization of BALB/c and C57 mice spleen cells and their fusion with Sp2/0 plasmacytoma cells. Besides rather low anti-IFN-beta or \"eps\" antibody secretion several cloned hybridoma fluids contained a factor potentiating anti-viral activity of the both IFNs. It is speculated that this activity is due to production by some hybridomas of another lymphokine."} {"id": "PMID:1282780", "title": "Autosomal dominant insulin resistance syndrome due to postbinding defect.", "content": "We investigated a family in which at least 4 men in 3 generations had a syndrome of obesity, mild mental retardation, delayed puberty, macroorchidism, acanthosis nigricans, hyperinsulinemia, and later overt insulin-resistant diabetes mellitus (non-insulin-dependent diabetes mellitus, NIDDM). The patients have markedly curly scalp hair, deficient face and body hair. Their teeth were healthy and normal in size and position. The clinical and biochemical findings and characteristics of the insulin receptors investigated in fibroblasts are reported. There was normal insulin binding to fibroblasts in the 2 brothers and their father. However, insulin-stimulated RNA synthesis was decreased as compared to that of normal control individuals. These findings suggest a postbinding defect of insulin action. The pedigree documents an autosomal dominant mode of inheritance. The diagnosis is of practical importance since it enables medical supervision of gene carriers in a preclinical state of atherosclerotic complications and overt diabetes. The findings in this family have relevance also to the explanation of familial mild mental retardation and to the study of different forms of insulin resistance due to a disturbance in biosignal transfer.", "contents": "Autosomal dominant insulin resistance syndrome due to postbinding defect. We investigated a family in which at least 4 men in 3 generations had a syndrome of obesity, mild mental retardation, delayed puberty, macroorchidism, acanthosis nigricans, hyperinsulinemia, and later overt insulin-resistant diabetes mellitus (non-insulin-dependent diabetes mellitus, NIDDM). The patients have markedly curly scalp hair, deficient face and body hair. Their teeth were healthy and normal in size and position. The clinical and biochemical findings and characteristics of the insulin receptors investigated in fibroblasts are reported. There was normal insulin binding to fibroblasts in the 2 brothers and their father. However, insulin-stimulated RNA synthesis was decreased as compared to that of normal control individuals. These findings suggest a postbinding defect of insulin action. The pedigree documents an autosomal dominant mode of inheritance. The diagnosis is of practical importance since it enables medical supervision of gene carriers in a preclinical state of atherosclerotic complications and overt diabetes. The findings in this family have relevance also to the explanation of familial mild mental retardation and to the study of different forms of insulin resistance due to a disturbance in biosignal transfer."} {"id": "PMID:1282781", "title": "Beta-adrenergic regulation of H+ secretion by cultured outer medullary collecting duct cells.", "content": "The effects of the beta-adrenergic agonist isoproterenol (Iso) on cells of the inner stripe portion of the rabbit outer medullary collecting duct (OMCDi) grown in primary culture were examined using whole cell patch-clamp techniques and measurements of intracellular pH (pHi) and Ca2+. Iso (10(-6) M) increased the cellular Cl- conductance, and this effect was mimicked by treatment of the cells with dibutyryladenosine 3',5'-cyclic monophosphate (cAMP, 10(-5) M) or protein kinase A (PKA, 0.4 U/ml). Iso did not alter the baseline pHi, but it did increase the activity of both the Cl-/HCO3- antiporter and the H(+)-adenosinetriphosphatase (H(+)-ATPase). The increase in Cl-/HCO3- antiporter rate was mimicked by dibutyryl-cAMP plus 3-isobutyl-1-methylxanthine (cAMP + IBMX, 10(-4) M + 10(-5) M). However, the Iso-induced stimulation of the H(+)-ATPase activity was not mimicked by cAMP + IBMX. Measurements of intracellular Ca2+ showed that Iso also increased intracellular Ca2+ levels. This response was not dependent on extracellular Ca2+, nor did cAMP + IBMX appreciably alter intracellular Ca2+. Consequently, we postulate that beta-adrenergic agonists are potential stimulators of OMCDi H+ secretion. These agonists stimulate cellular HCO3- efflux through a signal transduction pathway involving cAMP and PKA. However, a different signal transduction pathway appears to mediate the stimulation of cellular H+ efflux. This second pathway may involve an elevation of intracellular Ca2+.", "contents": "Beta-adrenergic regulation of H+ secretion by cultured outer medullary collecting duct cells. The effects of the beta-adrenergic agonist isoproterenol (Iso) on cells of the inner stripe portion of the rabbit outer medullary collecting duct (OMCDi) grown in primary culture were examined using whole cell patch-clamp techniques and measurements of intracellular pH (pHi) and Ca2+. Iso (10(-6) M) increased the cellular Cl- conductance, and this effect was mimicked by treatment of the cells with dibutyryladenosine 3',5'-cyclic monophosphate (cAMP, 10(-5) M) or protein kinase A (PKA, 0.4 U/ml). Iso did not alter the baseline pHi, but it did increase the activity of both the Cl-/HCO3- antiporter and the H(+)-adenosinetriphosphatase (H(+)-ATPase). The increase in Cl-/HCO3- antiporter rate was mimicked by dibutyryl-cAMP plus 3-isobutyl-1-methylxanthine (cAMP + IBMX, 10(-4) M + 10(-5) M). However, the Iso-induced stimulation of the H(+)-ATPase activity was not mimicked by cAMP + IBMX. Measurements of intracellular Ca2+ showed that Iso also increased intracellular Ca2+ levels. This response was not dependent on extracellular Ca2+, nor did cAMP + IBMX appreciably alter intracellular Ca2+. Consequently, we postulate that beta-adrenergic agonists are potential stimulators of OMCDi H+ secretion. These agonists stimulate cellular HCO3- efflux through a signal transduction pathway involving cAMP and PKA. However, a different signal transduction pathway appears to mediate the stimulation of cellular H+ efflux. This second pathway may involve an elevation of intracellular Ca2+."} {"id": "PMID:1282782", "title": "Extent and course of glomerular injury in human membranous glomerulopathy.", "content": "Glomerular permselectivity and dynamics were evaluated serially in 14 nephrotic patients with membranous glomerulopathy (MG). Analysis of transglomerular dextran sieving, before and again after proteinuria remitted, revealed persistent depression by 60-80% of glomerular pore density and the two-kidney ultrafiltration coefficient, Kf. The glomerular filtration rate was lowered by half on each occasion. Morphometric examination of glomeruli in a second group of 16 nephrotic patients with MG revealed a low prevalence of glomerulosclerosis (5 +/- 3%) and a twofold increase in filtration surface due to marked glomerular hypertrophy. Presumably, widening by threefold of the basement membrane and/or epithelial podocytes accounted for the computed reduction in ultrafiltration capacity. There was no correlation between glomerular structure and the subsequent course of MG over the ensuing 24-96 mo. Rather, a twofold expansion of the interstitial compartment predicted those who went on to exhibit progressive renal insufficiency. We conclude that increasing resistance to water flow by walls of patent and perfused glomerular capillaries is the proximate cause of progressive renal insufficiency in MG.", "contents": "Extent and course of glomerular injury in human membranous glomerulopathy. Glomerular permselectivity and dynamics were evaluated serially in 14 nephrotic patients with membranous glomerulopathy (MG). Analysis of transglomerular dextran sieving, before and again after proteinuria remitted, revealed persistent depression by 60-80% of glomerular pore density and the two-kidney ultrafiltration coefficient, Kf. The glomerular filtration rate was lowered by half on each occasion. Morphometric examination of glomeruli in a second group of 16 nephrotic patients with MG revealed a low prevalence of glomerulosclerosis (5 +/- 3%) and a twofold increase in filtration surface due to marked glomerular hypertrophy. Presumably, widening by threefold of the basement membrane and/or epithelial podocytes accounted for the computed reduction in ultrafiltration capacity. There was no correlation between glomerular structure and the subsequent course of MG over the ensuing 24-96 mo. Rather, a twofold expansion of the interstitial compartment predicted those who went on to exhibit progressive renal insufficiency. We conclude that increasing resistance to water flow by walls of patent and perfused glomerular capillaries is the proximate cause of progressive renal insufficiency in MG."} {"id": "PMID:1282783", "title": "Force-frequency relations and response to ryanodine in failing rabbit hearts.", "content": "Force-frequency relations were studied in an isolated-perfused rabbit heart model. Heart failure was induced by a double volume plus pressure overload. Studies were performed at the early stage of heart failure when basal ventricular function was not decreased. The normal positive staircase induced by pacing in control hearts (CH) was replaced by a negative staircase in failing hearts (FH) with an increase in end-diastolic pressure for increased heart rates in FH. Postpacing potentiation and postextrasystolic potentiation (PESP) were significantly reduced in FH as compared with CH. Ventricular function decreased by 60% in both CH and FH under ryanodine with similar dose-response curves. Postpacing and PESP disappeared under ryanodine in CH and in FH with a reversal of the negative staircase in FH. The abnormal force-frequency relations observed in heart failure are thus attributed to sarcoplasmic reticulum dysfunction. Basal ventricular function during spontaneous heart rate may be normal in the early stage of heart failure, but sarcoplasmic reticulum dysfunction produces abnormalities in ventricular function when heart rate is abruptly modified, particularly during tachycardia.", "contents": "Force-frequency relations and response to ryanodine in failing rabbit hearts. Force-frequency relations were studied in an isolated-perfused rabbit heart model. Heart failure was induced by a double volume plus pressure overload. Studies were performed at the early stage of heart failure when basal ventricular function was not decreased. The normal positive staircase induced by pacing in control hearts (CH) was replaced by a negative staircase in failing hearts (FH) with an increase in end-diastolic pressure for increased heart rates in FH. Postpacing potentiation and postextrasystolic potentiation (PESP) were significantly reduced in FH as compared with CH. Ventricular function decreased by 60% in both CH and FH under ryanodine with similar dose-response curves. Postpacing and PESP disappeared under ryanodine in CH and in FH with a reversal of the negative staircase in FH. The abnormal force-frequency relations observed in heart failure are thus attributed to sarcoplasmic reticulum dysfunction. Basal ventricular function during spontaneous heart rate may be normal in the early stage of heart failure, but sarcoplasmic reticulum dysfunction produces abnormalities in ventricular function when heart rate is abruptly modified, particularly during tachycardia."} {"id": "PMID:1282784", "title": "Ca(2+)-dependent and Ca(2+)-permeable ion channels in aortic endothelial cells.", "content": "We investigated whether osmotic stress would activate specific ion channels in bovine aortic endothelial cells (BAECs). In isotonic medium (290 mosmol/kgH2O), cell-attached patch recordings contained both 165-pS K+ channels activated by depolarization and 40-pS K+ channels activated by 200 nM bradykinin. These inwardly rectifying K+ channels were activated by raising \"cytoplasmic\" Ca2+ in inside-out patches. BAEC exposed to hypotonic bath (220 mosmol/kg) exhibited a 20% decrease in intracellular K+ content within 5 min. Cell-attached patches revealed biphasic K+ channel activation with hypotonic exposure; initial activation of 165- and 40-pS K+ channels (1-3 min) was followed by a delayed but sustained reactivation of both K+ channels (> 5 min). The delayed reactivation phase was dependent on the presence of external Ca2+ and was attenuated by 10 microM gadolinium. A 28-pS nonselective cation channel (NSCC), which conducted inward Ca2+ current, was also detected during hypotonic exposure. This NSCC was stimulated by hyperpolarization and was blocked by 10 microM gadolinium. In BAEC 1) hypotonic exposure activates Ca(2+)-dependent, 165- and 40-pS K+ channels biphasically; 2) the initial phase is independent of external Ca2+, while the delayed phase requires external Ca2+; and 3) Ca(2+)-permeable, 28-pS NSCCs stimulated by membrane hyperpolarization provide a pathway for external Ca2+ influx.", "contents": "Ca(2+)-dependent and Ca(2+)-permeable ion channels in aortic endothelial cells. We investigated whether osmotic stress would activate specific ion channels in bovine aortic endothelial cells (BAECs). In isotonic medium (290 mosmol/kgH2O), cell-attached patch recordings contained both 165-pS K+ channels activated by depolarization and 40-pS K+ channels activated by 200 nM bradykinin. These inwardly rectifying K+ channels were activated by raising \"cytoplasmic\" Ca2+ in inside-out patches. BAEC exposed to hypotonic bath (220 mosmol/kg) exhibited a 20% decrease in intracellular K+ content within 5 min. Cell-attached patches revealed biphasic K+ channel activation with hypotonic exposure; initial activation of 165- and 40-pS K+ channels (1-3 min) was followed by a delayed but sustained reactivation of both K+ channels (> 5 min). The delayed reactivation phase was dependent on the presence of external Ca2+ and was attenuated by 10 microM gadolinium. A 28-pS nonselective cation channel (NSCC), which conducted inward Ca2+ current, was also detected during hypotonic exposure. This NSCC was stimulated by hyperpolarization and was blocked by 10 microM gadolinium. In BAEC 1) hypotonic exposure activates Ca(2+)-dependent, 165- and 40-pS K+ channels biphasically; 2) the initial phase is independent of external Ca2+, while the delayed phase requires external Ca2+; and 3) Ca(2+)-permeable, 28-pS NSCCs stimulated by membrane hyperpolarization provide a pathway for external Ca2+ influx."} {"id": "PMID:1282785", "title": "Microvascular ischemia-reperfusion injury in striated muscle: significance of \"reflow paradox\".", "content": "Ischemia-reperfusion (I/R)-induced microvascular injury is characterized by capillary \"no-reflow\" and reflow-associated events, termed \"reflow paradox,\" including leukocyte-endothelium interaction and increase in microvascular permeability. The major objectives of this study were 1) to elucidate the significance of reflow paradox after 4 h of tourniquet-induced ischemia in striated muscle and 2) to determine the role of reactive oxygen metabolites in the pathogenesis of reflow paradox-dependent microcirculatory alterations. By use of in vivo fluorescence microscopy in a striated muscle preparation of hamsters, leukocyte-endothelium interaction in postcapillary venules and macromolecular extravasation from capillaries and venules were quantified before ischemia and after 30 min, 2 h, and 24 h of reperfusion. I/R elicited marked enhancement (P < 0.01) of leukocyte rolling during initial reperfusion and a 20-fold increase of leukocyte adherence (P < 0.01) lasting for the entire postischemic reperfusion period (n = 7). These phenomena were accompanied by significant leakage (P < 0.01) of macromolecules from capillaries and in particular from postcapillary venules (n = 9). Both superoxide dismutase (SOD, 20 mg/kg body wt, n = 7) and allopurinol (50 mg/kg body wt, n = 7) were effective in attenuating I/R-induced leukocyte rolling and adherence. In addition, microvascular leakage was significantly reduced by allopurinol (n = 9) and completely abolished by SOD (n = 9) (P < 0.01). These results support the concept that reactive oxygen metabolites contribute to I/R-induced reflow paradox, resulting in leukocyte accumulation, adherence, and increase in microvascular permeability.", "contents": "Microvascular ischemia-reperfusion injury in striated muscle: significance of \"reflow paradox\". Ischemia-reperfusion (I/R)-induced microvascular injury is characterized by capillary \"no-reflow\" and reflow-associated events, termed \"reflow paradox,\" including leukocyte-endothelium interaction and increase in microvascular permeability. The major objectives of this study were 1) to elucidate the significance of reflow paradox after 4 h of tourniquet-induced ischemia in striated muscle and 2) to determine the role of reactive oxygen metabolites in the pathogenesis of reflow paradox-dependent microcirculatory alterations. By use of in vivo fluorescence microscopy in a striated muscle preparation of hamsters, leukocyte-endothelium interaction in postcapillary venules and macromolecular extravasation from capillaries and venules were quantified before ischemia and after 30 min, 2 h, and 24 h of reperfusion. I/R elicited marked enhancement (P < 0.01) of leukocyte rolling during initial reperfusion and a 20-fold increase of leukocyte adherence (P < 0.01) lasting for the entire postischemic reperfusion period (n = 7). These phenomena were accompanied by significant leakage (P < 0.01) of macromolecules from capillaries and in particular from postcapillary venules (n = 9). Both superoxide dismutase (SOD, 20 mg/kg body wt, n = 7) and allopurinol (50 mg/kg body wt, n = 7) were effective in attenuating I/R-induced leukocyte rolling and adherence. In addition, microvascular leakage was significantly reduced by allopurinol (n = 9) and completely abolished by SOD (n = 9) (P < 0.01). These results support the concept that reactive oxygen metabolites contribute to I/R-induced reflow paradox, resulting in leukocyte accumulation, adherence, and increase in microvascular permeability."} {"id": "PMID:1282786", "title": "Interferons and central regulation of feeding.", "content": "Interferons (IFNs) are immunomodulators with neuromodulatory activities. To study the effects of IFNs on the central regulation of feeding, rats were subjected to various applications. The results show the following. 1) Intracerebroventricular microinfusion of rat IFN (15-225 IU/rat) decreased short-term (2-h) food intake in rats. Computerized analysis of behavioral patterns demonstrated a reduction of meal size and meal duration, whereas meal frequency slightly increased. Nighttime and total daily food intakes were not significantly affected. 2) Short-term food intake suppression by intracerebroventricular rat IFN was accompanied by a small increase in cerebrospinal fluid and rectal temperatures. 3) Intracerebroventricular microinfusion of heat-treated rat IFN or of recombinant human interferon-alpha (rhIFN-alpha) did not affect food intake. Only one dose of rhIFN-gamma (400 ng/rat) decreased 2-h food intake. These results are consistent with the species specificity to the effects of IFNs. 4) Peripheral administration of rat IFN in doses equivalent to those administered centrally had no effect on food intake. The results suggest that IFN acts directly in the central nervous system to decrease short-term feeding.", "contents": "Interferons and central regulation of feeding. Interferons (IFNs) are immunomodulators with neuromodulatory activities. To study the effects of IFNs on the central regulation of feeding, rats were subjected to various applications. The results show the following. 1) Intracerebroventricular microinfusion of rat IFN (15-225 IU/rat) decreased short-term (2-h) food intake in rats. Computerized analysis of behavioral patterns demonstrated a reduction of meal size and meal duration, whereas meal frequency slightly increased. Nighttime and total daily food intakes were not significantly affected. 2) Short-term food intake suppression by intracerebroventricular rat IFN was accompanied by a small increase in cerebrospinal fluid and rectal temperatures. 3) Intracerebroventricular microinfusion of heat-treated rat IFN or of recombinant human interferon-alpha (rhIFN-alpha) did not affect food intake. Only one dose of rhIFN-gamma (400 ng/rat) decreased 2-h food intake. These results are consistent with the species specificity to the effects of IFNs. 4) Peripheral administration of rat IFN in doses equivalent to those administered centrally had no effect on food intake. The results suggest that IFN acts directly in the central nervous system to decrease short-term feeding."} {"id": "PMID:1282787", "title": "A specific stain for the detection of nonheme iron proteins in polyacrylamide gels.", "content": "Nonheme iron proteins can be visualized as blue bands in native polyacrylamide gels using a staining method that is both simple and rapid. The reaction of potassium ferricyanide with protein-bound iron atoms to form royal blue complexes occurs almost instantaneously and is sensitive enough to detect 1 microgram of analytical-grade ferritin and 2 micrograms of purified ferredoxin from cyanobacteria. No special treatment of reagents or apparatus was necessary. On comparison, this stain was found to be more specific than the Ferene S stain, not detecting bovine serum albumin even when present as a hundredfold excess over ferritin. The method was found to be effective for isoelectric focusing gels as well.", "contents": "A specific stain for the detection of nonheme iron proteins in polyacrylamide gels. Nonheme iron proteins can be visualized as blue bands in native polyacrylamide gels using a staining method that is both simple and rapid. The reaction of potassium ferricyanide with protein-bound iron atoms to form royal blue complexes occurs almost instantaneously and is sensitive enough to detect 1 microgram of analytical-grade ferritin and 2 micrograms of purified ferredoxin from cyanobacteria. No special treatment of reagents or apparatus was necessary. On comparison, this stain was found to be more specific than the Ferene S stain, not detecting bovine serum albumin even when present as a hundredfold excess over ferritin. The method was found to be effective for isoelectric focusing gels as well."} {"id": "PMID:1282790", "title": "Cell type-specific anti-human immunodeficiency virus type 1 activity of the transactivation inhibitor Ro5-3335.", "content": "The drug Ro5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepin-2(H)-one] inhibits human immunodeficiency virus type 1 (HIV-1) gene expression at the transcriptional level through interference with Tat-mediated transactivation (M.-C. Hsu, A. D. Schutt, M. Holly, L. W. Slice, M. I. Sherman, D. D. Richman, M. J. Potash, and D. J. Volsky, Science 254:1799-1802, 1991). We confirmed this specific inhibitory effect in a quantitative bioassay based on transactivation of a chimeric gene comprising the HIV-1 long terminal repeat promoter fused to the lacZ gene of Escherichia coli and transfected in a HeLa cell line expressing Tat. Ro5-3335 was found to inhibit HIV-1 long terminal repeat-driven lacZ gene expression at a 50% inhibitory concentration of 0.5 microM. The in vitro anti-HIV-1 activity of Ro5-3335 was highly dependent on the nature of the host cells. The highest selectivity index, 50, was found in phytohemagglutinin-stimulated peripheral blood lymphocytes. The selectivity index was between 1 and 10 in the CD4+ T-cell lines CEM, MOLT-4 (clone 8), and HUT-78. In MT-4 and MT-2 cells, Ro5-3335 had no inhibitory effect on HIV-1 replication. The absence of anti-HIV-1 activity of Ro5-3335 in MT-4 cells was confirmed by using different parameters of virus replication and different multiplicities of infection. In persistently HIV-1-infected HUT-78/IIIB/LAI cells, Ro5-3335 failed to demonstrate any activity at subtoxic concentrations. The cytotoxicity of Ro5-3335 was significantly lower in peripheral blood lymphocytes than in the CD4+ T-cell lines.", "contents": "Cell type-specific anti-human immunodeficiency virus type 1 activity of the transactivation inhibitor Ro5-3335. The drug Ro5-3335 [7-chloro-5-(2-pyrryl)-3H-1,4-benzodiazepin-2(H)-one] inhibits human immunodeficiency virus type 1 (HIV-1) gene expression at the transcriptional level through interference with Tat-mediated transactivation (M.-C. Hsu, A. D. Schutt, M. Holly, L. W. Slice, M. I. Sherman, D. D. Richman, M. J. Potash, and D. J. Volsky, Science 254:1799-1802, 1991). We confirmed this specific inhibitory effect in a quantitative bioassay based on transactivation of a chimeric gene comprising the HIV-1 long terminal repeat promoter fused to the lacZ gene of Escherichia coli and transfected in a HeLa cell line expressing Tat. Ro5-3335 was found to inhibit HIV-1 long terminal repeat-driven lacZ gene expression at a 50% inhibitory concentration of 0.5 microM. The in vitro anti-HIV-1 activity of Ro5-3335 was highly dependent on the nature of the host cells. The highest selectivity index, 50, was found in phytohemagglutinin-stimulated peripheral blood lymphocytes. The selectivity index was between 1 and 10 in the CD4+ T-cell lines CEM, MOLT-4 (clone 8), and HUT-78. In MT-4 and MT-2 cells, Ro5-3335 had no inhibitory effect on HIV-1 replication. The absence of anti-HIV-1 activity of Ro5-3335 in MT-4 cells was confirmed by using different parameters of virus replication and different multiplicities of infection. In persistently HIV-1-infected HUT-78/IIIB/LAI cells, Ro5-3335 failed to demonstrate any activity at subtoxic concentrations. The cytotoxicity of Ro5-3335 was significantly lower in peripheral blood lymphocytes than in the CD4+ T-cell lines."} {"id": "PMID:1282791", "title": "The role of guanosine-3',5'-bis-pyrophosphate in mediating antimicrobial activity of the antibiotic 3,5-dihydroxy-4-ethyl-trans-stilbene.", "content": "The mode of action of 3,5-dihydroxy-4-ethyl-trans-stilbene (ES), an antibiotic produced by Xenorhabdus luminescens symbiotically associated with an entomopathogenic nematode, was investigated. ES was active against gram-positive and a number of gram-negative bacteria. In susceptible bacteria this antibiotic caused the inhibition of total RNA synthesis and, to a lesser extent, protein synthesis. At or above MICs, ES triggered a substantial accumulation of an intracellular regulatory compound, guanosine-3',5'-bis-pyrophosphate (ppGpp). This response was also noticed in species of bacteria which have previously not been shown to use ppGpp as a regulatory molecule. The involvement of ppGpp in antibiotic action was confirmed by using an isogenic stringent and a relaxed pair of Escherichia coli strains. The fact that the accumulation of ppGpp was correlated with the susceptibility of various gram-positive and gram-negative bacteria to ES suggests that this nucleotide is involved in the regulation of RNA synthesis and growth in all these microorganisms. Thus, inhibition of RNA synthesis via an increase in ppGpp concentrations may represent a mechanism that is prevalent among most bacteria and one that could be exploited for achieving a rapid inhibition of bacterial growth.", "contents": "The role of guanosine-3',5'-bis-pyrophosphate in mediating antimicrobial activity of the antibiotic 3,5-dihydroxy-4-ethyl-trans-stilbene. The mode of action of 3,5-dihydroxy-4-ethyl-trans-stilbene (ES), an antibiotic produced by Xenorhabdus luminescens symbiotically associated with an entomopathogenic nematode, was investigated. ES was active against gram-positive and a number of gram-negative bacteria. In susceptible bacteria this antibiotic caused the inhibition of total RNA synthesis and, to a lesser extent, protein synthesis. At or above MICs, ES triggered a substantial accumulation of an intracellular regulatory compound, guanosine-3',5'-bis-pyrophosphate (ppGpp). This response was also noticed in species of bacteria which have previously not been shown to use ppGpp as a regulatory molecule. The involvement of ppGpp in antibiotic action was confirmed by using an isogenic stringent and a relaxed pair of Escherichia coli strains. The fact that the accumulation of ppGpp was correlated with the susceptibility of various gram-positive and gram-negative bacteria to ES suggests that this nucleotide is involved in the regulation of RNA synthesis and growth in all these microorganisms. Thus, inhibition of RNA synthesis via an increase in ppGpp concentrations may represent a mechanism that is prevalent among most bacteria and one that could be exploited for achieving a rapid inhibition of bacterial growth."} {"id": "PMID:1282792", "title": "3'-Azido-3'-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside reverse transcriptase inhibitors.", "content": "Nonnucleoside reverse transcriptase (NNRT) inhibitors (R82913; (+)-S-4,5,6,7-tetrahydro-9-chloro-5-methyl-6-(3-methyl-2-butenyl)- imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione; Cl-TIBO; and BI-RG-587, nevirapine) were used to select resistant human immunodeficiency virus type 1 (HIV-1) variants by passage in cell cultures of wild-type or 3'-azido-3'-deoxythymidine (zidovudine; AZT)-resistant strains. Similar to other NNRT inhibitors, Cl-TIBO induced a single mutation (Y181 to C) in reverse transcriptase (RT) that accounted for the resistance. BI-RG-587 induced a different mutation (V106-->A) in AZT resistance backgrounds. A series of viable HIV-1 variants was constructed by site-directed mutagenesis of the RT, which harbored multiple drug resistance mutations, including Y181 to C. HIV-1 that was co-resistant to NNRT inhibitors and 2',3'-dideoxyinosine resulted when a 2',3'-dideoxyinosine resistance mutation (L74 to V) was also present in RT. By contrast, however, the Y181 to C mutation in an AZT resistance background significantly suppressed resistance to AZT, while it conferred resistance to NNRT inhibitors. However, the V106-->A substitution did not cause suppression of preexisting AZT resistance. Since certain combinations of nucleoside analogs and NNRT inhibitors might result in the development of co-resistance, careful analysis of clinical isolates obtained during combination therapy will be needed to determine the potential significance of these observations.", "contents": "3'-Azido-3'-deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside reverse transcriptase inhibitors. Nonnucleoside reverse transcriptase (NNRT) inhibitors (R82913; (+)-S-4,5,6,7-tetrahydro-9-chloro-5-methyl-6-(3-methyl-2-butenyl)- imidazo[4,5,1-jk][1,4]-benzodiazepin-2(1H)-thione; Cl-TIBO; and BI-RG-587, nevirapine) were used to select resistant human immunodeficiency virus type 1 (HIV-1) variants by passage in cell cultures of wild-type or 3'-azido-3'-deoxythymidine (zidovudine; AZT)-resistant strains. Similar to other NNRT inhibitors, Cl-TIBO induced a single mutation (Y181 to C) in reverse transcriptase (RT) that accounted for the resistance. BI-RG-587 induced a different mutation (V106-->A) in AZT resistance backgrounds. A series of viable HIV-1 variants was constructed by site-directed mutagenesis of the RT, which harbored multiple drug resistance mutations, including Y181 to C. HIV-1 that was co-resistant to NNRT inhibitors and 2',3'-dideoxyinosine resulted when a 2',3'-dideoxyinosine resistance mutation (L74 to V) was also present in RT. By contrast, however, the Y181 to C mutation in an AZT resistance background significantly suppressed resistance to AZT, while it conferred resistance to NNRT inhibitors. However, the V106-->A substitution did not cause suppression of preexisting AZT resistance. Since certain combinations of nucleoside analogs and NNRT inhibitors might result in the development of co-resistance, careful analysis of clinical isolates obtained during combination therapy will be needed to determine the potential significance of these observations."} {"id": "PMID:1282793", "title": "Cell surface characteristics of environmental and clinical isolates of Vibrio cholerae non-O1.", "content": "The cell surfaces of several toxigenic and nontoxigenic environmental and clinical isolates of Vibrio cholerae non-O1 have been examined. The environmental strains, irrespective of toxigenicity, are significantly more resistant to antibiotics and detergents than are V. cholerae O1 strains. The clinical isolates of non-O1 vibrios are as sensitive to a wide variety of chemicals as the O1 vibrios. The environmental non-O1 strains are also less susceptible to lysis when treated with protein denaturants or neutral and anionic detergents than are O1 vibrios and the clinical non-O1 strains. In contrast to O1 vibrios, the environmental non-O1 vibrios do not have exposed phospholipids in their outer membranes. These features of the cell surfaces of environmental non-O1 vibrios might have a role in the better survival of these organisms under environmental fluctuations.", "contents": "Cell surface characteristics of environmental and clinical isolates of Vibrio cholerae non-O1. The cell surfaces of several toxigenic and nontoxigenic environmental and clinical isolates of Vibrio cholerae non-O1 have been examined. The environmental strains, irrespective of toxigenicity, are significantly more resistant to antibiotics and detergents than are V. cholerae O1 strains. The clinical isolates of non-O1 vibrios are as sensitive to a wide variety of chemicals as the O1 vibrios. The environmental non-O1 strains are also less susceptible to lysis when treated with protein denaturants or neutral and anionic detergents than are O1 vibrios and the clinical non-O1 strains. In contrast to O1 vibrios, the environmental non-O1 vibrios do not have exposed phospholipids in their outer membranes. These features of the cell surfaces of environmental non-O1 vibrios might have a role in the better survival of these organisms under environmental fluctuations."} {"id": "PMID:1282796", "title": "[Sclerosis and carcinogenesis].", "content": "Morphological analysis of the sclerotic changes in peripheral lung carcinoma (PLC) and nephrosclerosis in renal-cell carcinoma (RCC) established a promoting role of sclerosis in carcinoma development. The pneumosclerosis role as a background process in the PLC development is proved by the following facts: high proportion (83%) of the carcinoma in the scar among PLC; identity of the scar collagen composition in PLC and that in metatuberculosis and metapneumonic pneumosclerosis foci; detection of metatuberculosis foci in 75% of PLC; the presence of the precancerous changes in the epithelium entrapped in the pneumosclerotic foci, not only with signs of morphological atypia, but with the disturbance of nuclear DNA and cellular oncogene expression as well. The association of RCC with nephrosclerosis is shown by a high proportion (82.7%) of the RCC development against the background of nephrosclerosis; the dependence of the so-called cortical adenoma development on the degree of nephrosclerosis; epithelial proliferation in the nephrosclerotic foci with the appearance of undifferentiated cells with the altered DNA content and the expression of cytokeratins and vimentine. Carcinoma morphogenesis against the background of sclerosis may be described as follows: development of sclerosis (focal and/or diffuse), the appearance of the focal epithelial hyperplasia in the scar, dysplasia or adenoma and finally carcinoma.", "contents": "[Sclerosis and carcinogenesis]. Morphological analysis of the sclerotic changes in peripheral lung carcinoma (PLC) and nephrosclerosis in renal-cell carcinoma (RCC) established a promoting role of sclerosis in carcinoma development. The pneumosclerosis role as a background process in the PLC development is proved by the following facts: high proportion (83%) of the carcinoma in the scar among PLC; identity of the scar collagen composition in PLC and that in metatuberculosis and metapneumonic pneumosclerosis foci; detection of metatuberculosis foci in 75% of PLC; the presence of the precancerous changes in the epithelium entrapped in the pneumosclerotic foci, not only with signs of morphological atypia, but with the disturbance of nuclear DNA and cellular oncogene expression as well. The association of RCC with nephrosclerosis is shown by a high proportion (82.7%) of the RCC development against the background of nephrosclerosis; the dependence of the so-called cortical adenoma development on the degree of nephrosclerosis; epithelial proliferation in the nephrosclerotic foci with the appearance of undifferentiated cells with the altered DNA content and the expression of cytokeratins and vimentine. Carcinoma morphogenesis against the background of sclerosis may be described as follows: development of sclerosis (focal and/or diffuse), the appearance of the focal epithelial hyperplasia in the scar, dysplasia or adenoma and finally carcinoma."} {"id": "PMID:1282794", "title": "Prostatic specific antigen and immunoglobulin binding factor in human seminal plasma and prostate.", "content": "Antibodies raised against prostatic specific antigen (PSA) and immunoglobulin binding factor (IgBF) of human seminal plasma (SP) were used to localize the antigens in various tissues by Western blot. Both antigens were found only in the prostate, including benign prostatic hypertrophy and prostatic adenocarcinoma. The polyclonal anti-PSA antibodies stained five prostatic protein bands with estimated M(r) values of 10, 14, 22, 25, and 33 kD, whereas anti-IgBF antibodies stained a single 16-kD protein. No cross-reaction occurred between the two antibodies. When anti-PSA antibodies were used an additional protein with an estimated M(r) of 35 kD was detected in the extract of benign prostatic hypertrophy, but not with normal prostate or prostatic cancer. When SP and prostatic proteins were analyzed by SDS-PAGE under nonreducing condition and immunoblot with both antibodies, immunoreactive proteins with estimated M(r) of 125 and 140 kD, respectively, were stained, suggesting that both factors may be produced as an aggregated precursor molecule. Since IgBF was found only in the prostate, this component may be useful as a marker of prostatic tissue.", "contents": "Prostatic specific antigen and immunoglobulin binding factor in human seminal plasma and prostate. Antibodies raised against prostatic specific antigen (PSA) and immunoglobulin binding factor (IgBF) of human seminal plasma (SP) were used to localize the antigens in various tissues by Western blot. Both antigens were found only in the prostate, including benign prostatic hypertrophy and prostatic adenocarcinoma. The polyclonal anti-PSA antibodies stained five prostatic protein bands with estimated M(r) values of 10, 14, 22, 25, and 33 kD, whereas anti-IgBF antibodies stained a single 16-kD protein. No cross-reaction occurred between the two antibodies. When anti-PSA antibodies were used an additional protein with an estimated M(r) of 35 kD was detected in the extract of benign prostatic hypertrophy, but not with normal prostate or prostatic cancer. When SP and prostatic proteins were analyzed by SDS-PAGE under nonreducing condition and immunoblot with both antibodies, immunoreactive proteins with estimated M(r) of 125 and 140 kD, respectively, were stained, suggesting that both factors may be produced as an aggregated precursor molecule. Since IgBF was found only in the prostate, this component may be useful as a marker of prostatic tissue."} {"id": "PMID:1282797", "title": "Insulin-like growth factor binding proteins of equine serum.", "content": "Ligand blotting analysis of serum from the horse using radiolabelled IGF-I revealed a protein at 96 kDa which was not present in serum from goat, cow, sheep, deer or donkey. These latter species all displayed five labelled bands in the range 24 to 41 kDa. Conversely, these were only weakly labelled in serum from the horse. Size exclusion chromatography of horse serum pre-incubated with radiolabelled IGF-I revealed reduced binding in the 130-kDa peak compared with goat plasma, and ligand blotting analysis indicated the 96-kDa protein was present in this peak. The 96-kDa protein from horse serum binds IGF-I and IGF-II specifically and appears to be unique to this species. The nature of this protein is at present unknown.", "contents": "Insulin-like growth factor binding proteins of equine serum. Ligand blotting analysis of serum from the horse using radiolabelled IGF-I revealed a protein at 96 kDa which was not present in serum from goat, cow, sheep, deer or donkey. These latter species all displayed five labelled bands in the range 24 to 41 kDa. Conversely, these were only weakly labelled in serum from the horse. Size exclusion chromatography of horse serum pre-incubated with radiolabelled IGF-I revealed reduced binding in the 130-kDa peak compared with goat plasma, and ligand blotting analysis indicated the 96-kDa protein was present in this peak. The 96-kDa protein from horse serum binds IGF-I and IGF-II specifically and appears to be unique to this species. The nature of this protein is at present unknown."} {"id": "PMID:1282795", "title": "Enzymatic action of basic arginine amidases in human seminal plasma.", "content": "Three basic arginine amidases with different affinities to lima bean trypsin inhibitor (LBTI) and aprotinin affinity columns were separated in the middle molecular weight (MMW) preparation obtained from Cellulofine GCL-2000 gel filtration of CM-cellulose adsorbed human seminal plasma and were tentatively called basic human seminal plasma arginine amidase-L (BHSAA-L, with affinity to LBTI), -A (BHSAA-A, with affinity to aprotinin), and -TH (BHSAA-TH, without affinity to either). Some enzymatic properties were measured, including Ki values of LBTI and human seminal plasma proteinase inhibitor (HSP-PI) toward present enzymes. The Ki values of LBTI toward BHSAA-L and -TH were lower than those of HSP-PI and no Ki values for LBTI toward BHSAA-L were observed. The Km values of BHSAA-L and -A to some tripeptidyl-p-nitroanilide substrates seemed relatively lower than that of BHSAA-TH.", "contents": "Enzymatic action of basic arginine amidases in human seminal plasma. Three basic arginine amidases with different affinities to lima bean trypsin inhibitor (LBTI) and aprotinin affinity columns were separated in the middle molecular weight (MMW) preparation obtained from Cellulofine GCL-2000 gel filtration of CM-cellulose adsorbed human seminal plasma and were tentatively called basic human seminal plasma arginine amidase-L (BHSAA-L, with affinity to LBTI), -A (BHSAA-A, with affinity to aprotinin), and -TH (BHSAA-TH, without affinity to either). Some enzymatic properties were measured, including Ki values of LBTI and human seminal plasma proteinase inhibitor (HSP-PI) toward present enzymes. The Ki values of LBTI toward BHSAA-L and -TH were lower than those of HSP-PI and no Ki values for LBTI toward BHSAA-L were observed. The Km values of BHSAA-L and -A to some tripeptidyl-p-nitroanilide substrates seemed relatively lower than that of BHSAA-TH."} {"id": "PMID:1282798", "title": "Nuclear matrix-associated NMN adenylyltransferase activity in human placenta.", "content": "This paper presents data about the presence of the NMN adenylyltransferase at the nuclear matrix level of human placenta nuclei. It was found that 40-45% of the activity (depending on the extraction procedure) referred to the total nuclear NMN adenylyltransferase was tightly associated with this subnuclear compartment. The matrices purified by two different procedures exhibited DNA, RNA and protein contents comparable with those described in literature. Extensive digestion of human placenta nuclei with DNase I was not able to solubilize the NMN adenylyltransferase activity. Therefore, the data we present are consistent with the conclusion that a part of the total nuclear NMN adenylyltransferase is associated with the nuclear matrix.", "contents": "Nuclear matrix-associated NMN adenylyltransferase activity in human placenta. This paper presents data about the presence of the NMN adenylyltransferase at the nuclear matrix level of human placenta nuclei. It was found that 40-45% of the activity (depending on the extraction procedure) referred to the total nuclear NMN adenylyltransferase was tightly associated with this subnuclear compartment. The matrices purified by two different procedures exhibited DNA, RNA and protein contents comparable with those described in literature. Extensive digestion of human placenta nuclei with DNase I was not able to solubilize the NMN adenylyltransferase activity. Therefore, the data we present are consistent with the conclusion that a part of the total nuclear NMN adenylyltransferase is associated with the nuclear matrix."} {"id": "PMID:1282799", "title": "Expression of scavenger receptors on renal cell carcinoma cells in vitro.", "content": "Messenger RNAs and proteins of scavenger receptor thought to be macrophage specific protein were expressed in renal cell carcinoma (RCC) cells in vitro. Acetyl LDL was taken up into RCC cells and promoted the production of interleukin-6 (IL-6), an in vitro autocrine growth factor to proliferate the cells. These results suggested that RCC cells might have a scavenger pathway which has not yet been demonstrated except for macrophages.", "contents": "Expression of scavenger receptors on renal cell carcinoma cells in vitro. Messenger RNAs and proteins of scavenger receptor thought to be macrophage specific protein were expressed in renal cell carcinoma (RCC) cells in vitro. Acetyl LDL was taken up into RCC cells and promoted the production of interleukin-6 (IL-6), an in vitro autocrine growth factor to proliferate the cells. These results suggested that RCC cells might have a scavenger pathway which has not yet been demonstrated except for macrophages."} {"id": "PMID:1282800", "title": "The level of a transcription factor Sp1 is correlated with the expression of EGF receptor in human gastric carcinomas.", "content": "The expression of the transcription factor Sp1 and EGF receptor (EGFR) was examined on human gastric carcinoma cell lines and gastric carcinoma tissues as well as corresponding normal mucosa in order to clarify the mechanism of overexpression of EGFR gene without gene amplification. All 7 carcinoma cell lines expressed Sp1 mRNA, the levels of which were closely correlated with the expression of EGFR mRNA except for one cell line. The gel retardation analysis revealed that the levels of Sp1 mRNA were parallel to its DNA binding activities. In 18 surgical cases, 12 tumors expressed Sp1 mRNA at higher levels than normal mucosa. The cases with overexpression of Sp1 showed the high level of EGFR mRNA. These results suggest that overexpression of Sp1 in tumor cells may induce overexpression of EGFR without gene amplification in human gastric carcinomas.", "contents": "The level of a transcription factor Sp1 is correlated with the expression of EGF receptor in human gastric carcinomas. The expression of the transcription factor Sp1 and EGF receptor (EGFR) was examined on human gastric carcinoma cell lines and gastric carcinoma tissues as well as corresponding normal mucosa in order to clarify the mechanism of overexpression of EGFR gene without gene amplification. All 7 carcinoma cell lines expressed Sp1 mRNA, the levels of which were closely correlated with the expression of EGFR mRNA except for one cell line. The gel retardation analysis revealed that the levels of Sp1 mRNA were parallel to its DNA binding activities. In 18 surgical cases, 12 tumors expressed Sp1 mRNA at higher levels than normal mucosa. The cases with overexpression of Sp1 showed the high level of EGFR mRNA. These results suggest that overexpression of Sp1 in tumor cells may induce overexpression of EGFR without gene amplification in human gastric carcinomas."} {"id": "PMID:1282801", "title": "Cellular retinoic acid-binding protein type II is expressed in adult human osteoblasts and in adult liver.", "content": "In this study we have used a reverse transcription polymerase chain reaction (RT-PCR) to demonstrate that adult primary human osteoblasts and SaOS-2, a human osteosarcoma-derived cell line with osteoblastic properties, express cellular retinol-binding protein I (CRBP I), cellular retinoic acid-binding protein II (CRABP II), and very low levels of CRABP I. We also show that CRABP II is expressed in the adult liver, which does not express CRABP I. The results suggest that CRABP II is the important isoform in the adult bone as well as in the adult liver. Since the 9-cis retinoic acid receptor (RXR) alpha previously has been shown to be expressed predominantly in the liver, CRABP II might be involved in the transport of 9-cis retinoic acid to its nuclear receptor.", "contents": "Cellular retinoic acid-binding protein type II is expressed in adult human osteoblasts and in adult liver. In this study we have used a reverse transcription polymerase chain reaction (RT-PCR) to demonstrate that adult primary human osteoblasts and SaOS-2, a human osteosarcoma-derived cell line with osteoblastic properties, express cellular retinol-binding protein I (CRBP I), cellular retinoic acid-binding protein II (CRABP II), and very low levels of CRABP I. We also show that CRABP II is expressed in the adult liver, which does not express CRABP I. The results suggest that CRABP II is the important isoform in the adult bone as well as in the adult liver. Since the 9-cis retinoic acid receptor (RXR) alpha previously has been shown to be expressed predominantly in the liver, CRABP II might be involved in the transport of 9-cis retinoic acid to its nuclear receptor."} {"id": "PMID:1282802", "title": "Human 6-pyruvoyltetrahydropterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme.", "content": "6-Pyruvoyl-tetrahydropterin synthase (PTPS) is involved in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for enzymes such as the hepatic phenylalanine hydroxylase. BH4 deficiency causes malignant hyperphenylalaninemia. We cloned the human liver cDNA encoding PTPS. The coding region for PTPS contains 145 amino acids and predicts a polypeptide of 16'387 Da. The human amino acid sequence showed a 82% identity with the rat liver sequence. Expression of the cDNA in E. coli yielded the active enzyme and showed immunoreactivity with antibodies against the rat liver PTPS. This is the basis for the molecular understanding of BH4 deficiency in patients suffering from a defect in PTPS activity.", "contents": "Human 6-pyruvoyltetrahydropterin synthase: cDNA cloning and heterologous expression of the recombinant enzyme. 6-Pyruvoyl-tetrahydropterin synthase (PTPS) is involved in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for enzymes such as the hepatic phenylalanine hydroxylase. BH4 deficiency causes malignant hyperphenylalaninemia. We cloned the human liver cDNA encoding PTPS. The coding region for PTPS contains 145 amino acids and predicts a polypeptide of 16'387 Da. The human amino acid sequence showed a 82% identity with the rat liver sequence. Expression of the cDNA in E. coli yielded the active enzyme and showed immunoreactivity with antibodies against the rat liver PTPS. This is the basis for the molecular understanding of BH4 deficiency in patients suffering from a defect in PTPS activity."} {"id": "PMID:1282803", "title": "Molecular cloning of crustacean pigment dispersing hormone precursor.", "content": "The cDNA encoding the precursor of the pigment dispersing hormone (PDH) of the shore crab, Carcinus maenas, was isolated and sequenced. The precursor consists of a putative 22 amino acid signal peptide, a putative 33 residue peptide of unknown function, and the 18 amino acid mature PDH, followed by a Gly residue which serves as a possible amide donor. The deduced mature PDH amino acid sequence is identical to those of Uca pugilator and Cancer magister, previously determined by Edman degradation.", "contents": "Molecular cloning of crustacean pigment dispersing hormone precursor. The cDNA encoding the precursor of the pigment dispersing hormone (PDH) of the shore crab, Carcinus maenas, was isolated and sequenced. The precursor consists of a putative 22 amino acid signal peptide, a putative 33 residue peptide of unknown function, and the 18 amino acid mature PDH, followed by a Gly residue which serves as a possible amide donor. The deduced mature PDH amino acid sequence is identical to those of Uca pugilator and Cancer magister, previously determined by Edman degradation."} {"id": "PMID:1282804", "title": "Interleukin-4 enhances in vitro mineralization in human osteoblast-like cells.", "content": "The effect of human interleukin-4 (hIL-4) on mineralization in human osteoblast-like cells was investigated. Confluent cells were incubated with hIL-4 for 16 or 30 days in the presence or absence, respectively, of alpha-glycerophosphate (alpha-GP), which accelerates the mineralization process. hIL-4 (0.3 ng/ml) induced mineralization with 1.9-, 26- and 37-fold increases of hydroxyproline, calcium, and osteocalcin content, respectively, in the presence of alpha-GP. Mineralization was not induced with other cytokines, hIL-1, hIL-2, hIL-6, or mIL-4. hIL-4 also induced mineralization in the absence of alpha-GP in a manner different from that of 1 alpha, 25(OH)2 vitaminD3 (1,25(OH)2VD3). These findings suggest that IL-4 may play an important role in bone formation.", "contents": "Interleukin-4 enhances in vitro mineralization in human osteoblast-like cells. The effect of human interleukin-4 (hIL-4) on mineralization in human osteoblast-like cells was investigated. Confluent cells were incubated with hIL-4 for 16 or 30 days in the presence or absence, respectively, of alpha-glycerophosphate (alpha-GP), which accelerates the mineralization process. hIL-4 (0.3 ng/ml) induced mineralization with 1.9-, 26- and 37-fold increases of hydroxyproline, calcium, and osteocalcin content, respectively, in the presence of alpha-GP. Mineralization was not induced with other cytokines, hIL-1, hIL-2, hIL-6, or mIL-4. hIL-4 also induced mineralization in the absence of alpha-GP in a manner different from that of 1 alpha, 25(OH)2 vitaminD3 (1,25(OH)2VD3). These findings suggest that IL-4 may play an important role in bone formation."} {"id": "PMID:1282805", "title": "A Xenopus homologue of the human beta-amyloid precursor protein: developmental regulation of its gene expression.", "content": "Complimentary DNA clones have been isolated from Xenopus larva to delineate a protein highly homologous to the human beta-amyloid precursor protein (APP). Developmental change of Xenopus APP gene expression has been analyzed with molecular probes. From early oogenesis, there is a high accumulation of maternal APP. After fertilization, the mRNA is degraded, reaching a minimum level around the gastrula stage. Then zygotic transcription appears to be initiated, and this continues during the subsequent embryonic and larval stages. Splicing patterns differ between the maternal and zygotic transcripts. The ratio of mRNA including the protease inhibitor domain (PID) sequence is extremely low for the transcript of maternal origin as compared to that for the transcript of zygotic origin. These results suggest some roles for the APP molecule in Xenopus early development.", "contents": "A Xenopus homologue of the human beta-amyloid precursor protein: developmental regulation of its gene expression. Complimentary DNA clones have been isolated from Xenopus larva to delineate a protein highly homologous to the human beta-amyloid precursor protein (APP). Developmental change of Xenopus APP gene expression has been analyzed with molecular probes. From early oogenesis, there is a high accumulation of maternal APP. After fertilization, the mRNA is degraded, reaching a minimum level around the gastrula stage. Then zygotic transcription appears to be initiated, and this continues during the subsequent embryonic and larval stages. Splicing patterns differ between the maternal and zygotic transcripts. The ratio of mRNA including the protease inhibitor domain (PID) sequence is extremely low for the transcript of maternal origin as compared to that for the transcript of zygotic origin. These results suggest some roles for the APP molecule in Xenopus early development."} {"id": "PMID:1282806", "title": "Characterization of the human islet amyloid polypeptide/amylin gene transcripts: identification of a new polyadenylation site.", "content": "Islet amyloid polypeptide (IAPP) or Amylin is synthesized by the pancreatic beta-cells. IAPP is the major component of islet amyloid in the pancreas of patients with non-insulin-dependent diabetes mellitus. We report the composition and complete nucleotide sequence of the two human IAPP mRNAs of 1.6 and 2.1 kb. A new polyadenylation site was identified and shown to be used in generation of the 2.1 kb RNA. A previously identified polyadenylation signal is assigned to the 1.6 kb RNA. We exactly determined the major transcription start site, which is used in generation of these mRNAs. Lower abundance RNAs containing sequences located further upstream in the IAPP gene were also detected.", "contents": "Characterization of the human islet amyloid polypeptide/amylin gene transcripts: identification of a new polyadenylation site. Islet amyloid polypeptide (IAPP) or Amylin is synthesized by the pancreatic beta-cells. IAPP is the major component of islet amyloid in the pancreas of patients with non-insulin-dependent diabetes mellitus. We report the composition and complete nucleotide sequence of the two human IAPP mRNAs of 1.6 and 2.1 kb. A new polyadenylation site was identified and shown to be used in generation of the 2.1 kb RNA. A previously identified polyadenylation signal is assigned to the 1.6 kb RNA. We exactly determined the major transcription start site, which is used in generation of these mRNAs. Lower abundance RNAs containing sequences located further upstream in the IAPP gene were also detected."} {"id": "PMID:1282807", "title": "Rat hepatocyte hyaluronan/glycosaminoglycan binding proteins: evidence for distinct divalent cation-independent and divalent cation-dependent activities.", "content": "We have previously shown (Biochemistry, 29, 10425, 1990) that hepatocytes contain intracellular specific binding sites for hyaluronan (HA). Although HA-binding activity is not dependent on divalent cations, it is increased in the presence of Ca+2. Here we report that a novel photoaffinity HA derivative (ASD-HA) crosslinks specifically to different proteins in permeable cells in the presence or absence of Ca+2. With Ca+2 present, two proteins of approximately 24 kD and 43 kD were labeled. Additionally, a broad zone of specific crosslinking was observed in the region of 40-100 kD. However, in the presence of the chelator EGTA this zone was absent and the 24 and 43 kD proteins were also not cross-linked to the HA photoaffinity derivative. In the absence of Ca+2, only a 54 kD protein was specifically labeled. The results indicate that different intracellular hepatocyte proteins are responsible for the Ca+2-independent and the Ca+2-dependent binding of HA.", "contents": "Rat hepatocyte hyaluronan/glycosaminoglycan binding proteins: evidence for distinct divalent cation-independent and divalent cation-dependent activities. We have previously shown (Biochemistry, 29, 10425, 1990) that hepatocytes contain intracellular specific binding sites for hyaluronan (HA). Although HA-binding activity is not dependent on divalent cations, it is increased in the presence of Ca+2. Here we report that a novel photoaffinity HA derivative (ASD-HA) crosslinks specifically to different proteins in permeable cells in the presence or absence of Ca+2. With Ca+2 present, two proteins of approximately 24 kD and 43 kD were labeled. Additionally, a broad zone of specific crosslinking was observed in the region of 40-100 kD. However, in the presence of the chelator EGTA this zone was absent and the 24 and 43 kD proteins were also not cross-linked to the HA photoaffinity derivative. In the absence of Ca+2, only a 54 kD protein was specifically labeled. The results indicate that different intracellular hepatocyte proteins are responsible for the Ca+2-independent and the Ca+2-dependent binding of HA."} {"id": "PMID:1282808", "title": "Effects of calyculin A on amylase release in streptolysin-O permeabilized acinar cells.", "content": "The effects of the phosphatase inhibitors calyculin A and okadaic acid on amylase release from streptolysin-O permeabilized rat pancreatic acini were investigated. Both agents induced similar biphasic effects with moderate potentiation of calcium-stimulated amylase release at medium and strong inhibition at higher concentrations. Calyculin A was thirty times more potent than okadaic acid and at 100 nM totally inhibited calcium-induced amylase release while 3 microM okadaic acid reduced amylase release by 78%. 100nM calyculin A also completely inhibited GTP gamma S-potentiated amylase release and partially inhibited phorbol ester potentiated secretion. The data indicate that inhibition of a serine/threonine phosphatase, probably a type 1 phosphatase, leads to inhibition of calcium-induced amylase release in permeabilized pancreatic acini.", "contents": "Effects of calyculin A on amylase release in streptolysin-O permeabilized acinar cells. The effects of the phosphatase inhibitors calyculin A and okadaic acid on amylase release from streptolysin-O permeabilized rat pancreatic acini were investigated. Both agents induced similar biphasic effects with moderate potentiation of calcium-stimulated amylase release at medium and strong inhibition at higher concentrations. Calyculin A was thirty times more potent than okadaic acid and at 100 nM totally inhibited calcium-induced amylase release while 3 microM okadaic acid reduced amylase release by 78%. 100nM calyculin A also completely inhibited GTP gamma S-potentiated amylase release and partially inhibited phorbol ester potentiated secretion. The data indicate that inhibition of a serine/threonine phosphatase, probably a type 1 phosphatase, leads to inhibition of calcium-induced amylase release in permeabilized pancreatic acini."} {"id": "PMID:1282809", "title": "Regulation of the expression of lamins A and C is post-transcriptional in P19 embryonal carcinoma cells.", "content": "The polypeptide composition of the nuclear lamina can display important variations: undifferentiated cells express only lamin B and they acquire lamins A and C only after differentiation. We have analyzed the expression of lamins A and C in P19 pluripotent mouse embryonal carcinoma cells. Undifferentiated P19 cells are completely devoid of lamins A and C. We show that undifferentiated P19 cells contain low, but detectable steady-state levels of RNAs for lamins A and C that begin to increase by 24 h of retinoic acid-induced differentiation. However, the rate of transcription of the lamin A and C gene(s), analyzed by run-on transcription assays, remains unchanged during the differentiation process. These results demonstrate that, at least in P19 embryonal carcinoma cells, regulation of the expression of lamins A and C is a post-transcriptional event.", "contents": "Regulation of the expression of lamins A and C is post-transcriptional in P19 embryonal carcinoma cells. The polypeptide composition of the nuclear lamina can display important variations: undifferentiated cells express only lamin B and they acquire lamins A and C only after differentiation. We have analyzed the expression of lamins A and C in P19 pluripotent mouse embryonal carcinoma cells. Undifferentiated P19 cells are completely devoid of lamins A and C. We show that undifferentiated P19 cells contain low, but detectable steady-state levels of RNAs for lamins A and C that begin to increase by 24 h of retinoic acid-induced differentiation. However, the rate of transcription of the lamin A and C gene(s), analyzed by run-on transcription assays, remains unchanged during the differentiation process. These results demonstrate that, at least in P19 embryonal carcinoma cells, regulation of the expression of lamins A and C is a post-transcriptional event."} {"id": "PMID:1282810", "title": "Multi-recognition capability of E-selectin in a dynamic flow system, as evidenced by differential effects of sialidases and anti-carbohydrate antibodies on selectin-mediated cell adhesion at low vs. high wall shear stress: a preliminary note.", "content": "E-selectin has a \"multi-recognition\" capability in terms of epitope binding specificity, depending on adhesion conditions (static vs. low- or high-shear stress dynamic systems). Specifically, (i) adhesion based on expression of alpha 2-->3 sialylated Le(x) (SLe(x)) is prominent under static or low shear stress dynamic conditions; (ii) adhesion under high shear stress dynamic conditions does not depend on the known SLe(x) species, but rather on Lex with an adjacent unidentified sialosyl substitution, which shows different susceptibility to sialidases and antibodies compared to known SLe(x).", "contents": "Multi-recognition capability of E-selectin in a dynamic flow system, as evidenced by differential effects of sialidases and anti-carbohydrate antibodies on selectin-mediated cell adhesion at low vs. high wall shear stress: a preliminary note. E-selectin has a \"multi-recognition\" capability in terms of epitope binding specificity, depending on adhesion conditions (static vs. low- or high-shear stress dynamic systems). Specifically, (i) adhesion based on expression of alpha 2-->3 sialylated Le(x) (SLe(x)) is prominent under static or low shear stress dynamic conditions; (ii) adhesion under high shear stress dynamic conditions does not depend on the known SLe(x) species, but rather on Lex with an adjacent unidentified sialosyl substitution, which shows different susceptibility to sialidases and antibodies compared to known SLe(x)."} {"id": "PMID:1282811", "title": "A novel tyrosine kinase, hyk, expressed in murine embryonic stem cells.", "content": "To identify tyrosine kinases which play roles in mammalian early development, the 3' rapid amplification of cDNA ends (RACE) was performed on mouse embryonic stem (ES) cells. Among eight tyrosine kinases thus identified, we report here a novel tyrosine kinase, hyk (adhesion structures linked tyrosine kinase). The sequences of the 4.7 kb cDNA indicated the presence of RGD motif and three epidermal growth factor-like domains put between two immunoglobulin-like domains and three fibronectin type III domains in its extracellular region. It is strongly expressed in ES cells and later stages of embryos, but at low levels in midgestation embryos. It is also expressed at a low level in neural precursor cells from 10-day embryos, but at high levels in embryonic day 15 and neonatal brains. In adult tissues it is expressed ubiquitously.", "contents": "A novel tyrosine kinase, hyk, expressed in murine embryonic stem cells. To identify tyrosine kinases which play roles in mammalian early development, the 3' rapid amplification of cDNA ends (RACE) was performed on mouse embryonic stem (ES) cells. Among eight tyrosine kinases thus identified, we report here a novel tyrosine kinase, hyk (adhesion structures linked tyrosine kinase). The sequences of the 4.7 kb cDNA indicated the presence of RGD motif and three epidermal growth factor-like domains put between two immunoglobulin-like domains and three fibronectin type III domains in its extracellular region. It is strongly expressed in ES cells and later stages of embryos, but at low levels in midgestation embryos. It is also expressed at a low level in neural precursor cells from 10-day embryos, but at high levels in embryonic day 15 and neonatal brains. In adult tissues it is expressed ubiquitously."} {"id": "PMID:1282812", "title": "Modulation of trichosanthin antigenicity by coupling to dextran.", "content": "Trichosanthin (TCS) is a plant-derived type I ribosome-inactivating protein with a wide spectrum of biological and pharmacological activities. Recently, it was covalently coupled to dextran in order to prolong its half-life in plasma. The major biological activities were generally retained but at lower potency. The immunogenicity of the dextran-trichosanthin (DX-TCS) was compared to that of TCS itself in this study. The results showed that mice immunized with TCS produced 8 times as much TCS-reactive IgE than those immunized with DX-TCS. However, both TCS and DX-TCS immunization produced similar titers of TCS-reactive IgG. A trace of dextran-reactive IgG was detected in mice immunized with DX-TCS. Thus, coupling of TCS to dextran reduced its antigenicity but slightly enhanced that of dextran, and the conjugate elicited less IgE than TCS.", "contents": "Modulation of trichosanthin antigenicity by coupling to dextran. Trichosanthin (TCS) is a plant-derived type I ribosome-inactivating protein with a wide spectrum of biological and pharmacological activities. Recently, it was covalently coupled to dextran in order to prolong its half-life in plasma. The major biological activities were generally retained but at lower potency. The immunogenicity of the dextran-trichosanthin (DX-TCS) was compared to that of TCS itself in this study. The results showed that mice immunized with TCS produced 8 times as much TCS-reactive IgE than those immunized with DX-TCS. However, both TCS and DX-TCS immunization produced similar titers of TCS-reactive IgG. A trace of dextran-reactive IgG was detected in mice immunized with DX-TCS. Thus, coupling of TCS to dextran reduced its antigenicity but slightly enhanced that of dextran, and the conjugate elicited less IgE than TCS."} {"id": "PMID:1282813", "title": "Effect of cytochrome C oxidase and polyanions on the alkaline transition of ferricytochrome C.", "content": "Application of heparin, polyadenylate, polyglutamate and polygalacturonate resulted in changes in the electron absorption spectrum of cytochrome c that resembled those after cytochrome c oxidase application at neutral pH. The formed complexes of cytochrome c with polyanions retain the bond of Met-80 with heme iron. Cytochrome c oxidase and the polyanions increased the apparent pKa of alkaline transition of cytochrome c by an order of magnitude.", "contents": "Effect of cytochrome C oxidase and polyanions on the alkaline transition of ferricytochrome C. Application of heparin, polyadenylate, polyglutamate and polygalacturonate resulted in changes in the electron absorption spectrum of cytochrome c that resembled those after cytochrome c oxidase application at neutral pH. The formed complexes of cytochrome c with polyanions retain the bond of Met-80 with heme iron. Cytochrome c oxidase and the polyanions increased the apparent pKa of alkaline transition of cytochrome c by an order of magnitude."} {"id": "PMID:1282814", "title": "Inhibition of mite protease (Df-protease) with protease inhibitors.", "content": "A protease from house dust mite(Dermatophagoides farinae) having high specificity towards a substrate of blood coagulation factor XIIa catalyzes the activation of kallikrein-kinin system in plasma (Takahashi et al., 1990). To prevent the formation of kinin by the mite-protease, inhibition of the protease with its inhibitors was tested in vitro and in vivo. Its kinetic studies revealed that Ki values are 3.9 x 10(-10) M for aprotinin, 3.0 x 10(-9) M for soybean trypsin inhibitor (Kunitz) and 2.5 x 10(-8) M for gabexate mesylate. Enhancement of blood permeability in guinea pigs caused by the protease was markedly suppressed by these inhibitors.", "contents": "Inhibition of mite protease (Df-protease) with protease inhibitors. A protease from house dust mite(Dermatophagoides farinae) having high specificity towards a substrate of blood coagulation factor XIIa catalyzes the activation of kallikrein-kinin system in plasma (Takahashi et al., 1990). To prevent the formation of kinin by the mite-protease, inhibition of the protease with its inhibitors was tested in vitro and in vivo. Its kinetic studies revealed that Ki values are 3.9 x 10(-10) M for aprotinin, 3.0 x 10(-9) M for soybean trypsin inhibitor (Kunitz) and 2.5 x 10(-8) M for gabexate mesylate. Enhancement of blood permeability in guinea pigs caused by the protease was markedly suppressed by these inhibitors."} {"id": "PMID:1282815", "title": "Inhibition of EGF-induced gastric mucosal calcium channel phosphorylation by ebrotidine.", "content": "A gastric mucosal calcium channel-epidermal growth factor (EGF) receptor complex was isolated from solubilized epithelial cell membranes by means of a wheat germ agglutinin affinity. The complex, following reconstitution into phosphatidylcholine vesicles, exhibited active 45Ca2+ uptake as evidence by concentration-dependent response to the calcium channel activator BAY K8644, and the calcium channel antagonist PN200-110. The complex on the addition of EGF and ATP showed an increase in tyrosine phosphorylation of both a 55 and a 170kDa protein, while the vesicles containing the phosphorylated complex displayed a 48% greater 45Ca2+ uptake. The phosphorylation process was inhibited by an anti-ulcer agent, ebrotidine, which also interfered with the binding of EGF to calcium channel protein. The results suggest that ebrotidine protects the cellular integrity from calcium imbalance by modulating the EGF-stimulated gastric mucosal calcium channel activation.", "contents": "Inhibition of EGF-induced gastric mucosal calcium channel phosphorylation by ebrotidine. A gastric mucosal calcium channel-epidermal growth factor (EGF) receptor complex was isolated from solubilized epithelial cell membranes by means of a wheat germ agglutinin affinity. The complex, following reconstitution into phosphatidylcholine vesicles, exhibited active 45Ca2+ uptake as evidence by concentration-dependent response to the calcium channel activator BAY K8644, and the calcium channel antagonist PN200-110. The complex on the addition of EGF and ATP showed an increase in tyrosine phosphorylation of both a 55 and a 170kDa protein, while the vesicles containing the phosphorylated complex displayed a 48% greater 45Ca2+ uptake. The phosphorylation process was inhibited by an anti-ulcer agent, ebrotidine, which also interfered with the binding of EGF to calcium channel protein. The results suggest that ebrotidine protects the cellular integrity from calcium imbalance by modulating the EGF-stimulated gastric mucosal calcium channel activation."} {"id": "PMID:1282816", "title": "Staurosporine and calphostin-C inhibit the phorbol ester-induced decrease of protein kinase C activity in rat hepatocytes.", "content": "Two main forms of protein kinase C (PKC 1 and PKC 2) are detected in homogenates of rat hepatocytes using DEAE-cellulose column chromatography. The activity of these forms paradoxically, is rapidly decreased by treatment in vivo with phorbol myristate acetate (PMA). The dose-response curves to PMA for decreasing the activities of PKC 1 and 2 were shifted to the right by the potent and selective PKC inhibitors, staurosporine and calphostin-C. The decreases induced by 100 nM PMA were dose-dependently blocked by these inhibitors. It is concluded that activation of PKC is required and precedes such decreases in activity induced by the active phorbol ester.", "contents": "Staurosporine and calphostin-C inhibit the phorbol ester-induced decrease of protein kinase C activity in rat hepatocytes. Two main forms of protein kinase C (PKC 1 and PKC 2) are detected in homogenates of rat hepatocytes using DEAE-cellulose column chromatography. The activity of these forms paradoxically, is rapidly decreased by treatment in vivo with phorbol myristate acetate (PMA). The dose-response curves to PMA for decreasing the activities of PKC 1 and 2 were shifted to the right by the potent and selective PKC inhibitors, staurosporine and calphostin-C. The decreases induced by 100 nM PMA were dose-dependently blocked by these inhibitors. It is concluded that activation of PKC is required and precedes such decreases in activity induced by the active phorbol ester."} {"id": "PMID:1282817", "title": "The effects of p-chlorophenylalanine-induced serotonin synthesis inhibition and muscarinic blockade on the performance of rats in a 5-choice serial reaction time task.", "content": "The effects of serotonergic dysfunction induced by treatment with p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, and cholinergic dysfunction induced by scopolamine on the performance of adult rats in the 5-choice serial reaction time task measuring selective attention were studied. Food-deprived rats were trained to detect and respond to brief flashes of light presented randomly in one of five locations, until they reached a stable level of performance (about 4 months). Scopolamine 0.2 mg/kg produced a marked variation in the performance but did not, however, induce any consistent impairment in the discriminative accuracy. Other doses of scopolamine (0.05 and 0.1 mg/kg) or N-methyl-scopolamine 0.2 mg/kg, a peripheral muscarinic receptor antagonist, did not affect discriminative accuracy. Furthermore, scopolamine as well as N-methyl-scopolamine produced a number of other performance deficits, such as significantly decreased overall probability of responding and significantly increased response latencies. PCPA treatment induced an almost total depletion (> 99%) of frontal cortical serotonin and its major metabolite 5-HIAA and reduced the frontal cortical concentrations of noradrenaline (-30%) and dopamine (-42%). During baseline testing conditions, there was a trend for the discriminative accuracy to be decreased by PCPA, although this effect failed to reach significance (P = 0.07). Presenting the stimuli at unpredictable intervals or reducing the intensity of the visual stimulus impaired discriminative accuracy in both PCPA-treated and control rats. The decrease in discriminative accuracy induced by PCPA reached statistical significance when the stimuli were presented faster than normally or the intensity of the visual stimulus was reduced. PCPA treatment did not make the rats more susceptible to the effects of scopolamine on discriminative accuracy. However, PCPA treatment also induced a number of other performance deficits, resulting in a decreased overall tendency to respond. In summary, there is a statistically non-significant trend for the discriminative accuracy to be decreased by PCPA treatment under normal testing conditions, and as the discrimination task is made more difficult (stimulus intensity reduction, presentation of the stimuli at faster than normal rates), the deficit in discriminative accuracy produced by PCPA treatment is revealed. The results suggest a role for brain serotonin in the general organization of behavior.", "contents": "The effects of p-chlorophenylalanine-induced serotonin synthesis inhibition and muscarinic blockade on the performance of rats in a 5-choice serial reaction time task. The effects of serotonergic dysfunction induced by treatment with p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis, and cholinergic dysfunction induced by scopolamine on the performance of adult rats in the 5-choice serial reaction time task measuring selective attention were studied. Food-deprived rats were trained to detect and respond to brief flashes of light presented randomly in one of five locations, until they reached a stable level of performance (about 4 months). Scopolamine 0.2 mg/kg produced a marked variation in the performance but did not, however, induce any consistent impairment in the discriminative accuracy. Other doses of scopolamine (0.05 and 0.1 mg/kg) or N-methyl-scopolamine 0.2 mg/kg, a peripheral muscarinic receptor antagonist, did not affect discriminative accuracy. Furthermore, scopolamine as well as N-methyl-scopolamine produced a number of other performance deficits, such as significantly decreased overall probability of responding and significantly increased response latencies. PCPA treatment induced an almost total depletion (> 99%) of frontal cortical serotonin and its major metabolite 5-HIAA and reduced the frontal cortical concentrations of noradrenaline (-30%) and dopamine (-42%). During baseline testing conditions, there was a trend for the discriminative accuracy to be decreased by PCPA, although this effect failed to reach significance (P = 0.07). Presenting the stimuli at unpredictable intervals or reducing the intensity of the visual stimulus impaired discriminative accuracy in both PCPA-treated and control rats. The decrease in discriminative accuracy induced by PCPA reached statistical significance when the stimuli were presented faster than normally or the intensity of the visual stimulus was reduced. PCPA treatment did not make the rats more susceptible to the effects of scopolamine on discriminative accuracy. However, PCPA treatment also induced a number of other performance deficits, resulting in a decreased overall tendency to respond. In summary, there is a statistically non-significant trend for the discriminative accuracy to be decreased by PCPA treatment under normal testing conditions, and as the discrimination task is made more difficult (stimulus intensity reduction, presentation of the stimuli at faster than normal rates), the deficit in discriminative accuracy produced by PCPA treatment is revealed. The results suggest a role for brain serotonin in the general organization of behavior."} {"id": "PMID:1282818", "title": "Modulation of the rat mesolimbic dopamine pathway by neurokinins.", "content": "The locomotor activity (LMA) response induced after infusion of selective neurokinin (NK) agonists into the cell body (A10) and a terminal region of the mesolimbic pathway of the rat was investigated. Infusion of the NK1 receptor-selective agonist, GR73632, into the ventral tegmental area (VTA: A10) or the nucleus accumbens (NAS) significantly and dose-dependently increased basal LMA. Agonists selective for the NK2 and NK3 receptors, GR64349 and senktide respectively, had no effect on LMA after intra-NAS infusion. The LMA induced by GR73632 is mediated via dopamine (DA) since the response was abolished by haloperidol. From these studies it would appear that the elevated LMA reported previously after VTA or NAS administration of substance P probably occurs via NK1 receptors. Such data supports the notion that endogenous NKs are likely to be important in modulating the mesolimbic DA pathway and, as a consequence, compounds which antagonise their effects could be useful for the treatment of disorders associated with this system. However, simultaneous infusion of the NK1 agonists, +/- CP-96,345 and its analogue CPQ, into the VTA did not attenuate the LMA induced after intra-VTA infusion of GR73632. Co-infusion of the NK1 antagonist CPQ, but not +/- CP-96,345, attenuated the LMA response induced by GR73632 in the NAS. The apparent poor susceptibility of these responses to blockade by the recently developed non-peptide NK1 antagonists was unexpected but may reflect their poor affinity for the rat variant of the NK1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Modulation of the rat mesolimbic dopamine pathway by neurokinins. The locomotor activity (LMA) response induced after infusion of selective neurokinin (NK) agonists into the cell body (A10) and a terminal region of the mesolimbic pathway of the rat was investigated. Infusion of the NK1 receptor-selective agonist, GR73632, into the ventral tegmental area (VTA: A10) or the nucleus accumbens (NAS) significantly and dose-dependently increased basal LMA. Agonists selective for the NK2 and NK3 receptors, GR64349 and senktide respectively, had no effect on LMA after intra-NAS infusion. The LMA induced by GR73632 is mediated via dopamine (DA) since the response was abolished by haloperidol. From these studies it would appear that the elevated LMA reported previously after VTA or NAS administration of substance P probably occurs via NK1 receptors. Such data supports the notion that endogenous NKs are likely to be important in modulating the mesolimbic DA pathway and, as a consequence, compounds which antagonise their effects could be useful for the treatment of disorders associated with this system. However, simultaneous infusion of the NK1 agonists, +/- CP-96,345 and its analogue CPQ, into the VTA did not attenuate the LMA induced after intra-VTA infusion of GR73632. Co-infusion of the NK1 antagonist CPQ, but not +/- CP-96,345, attenuated the LMA response induced by GR73632 in the NAS. The apparent poor susceptibility of these responses to blockade by the recently developed non-peptide NK1 antagonists was unexpected but may reflect their poor affinity for the rat variant of the NK1 receptor.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282819", "title": "Amylase cis-acting sequences mediate the alleviation of glucose repression by cAMP in Drosophila.", "content": "alpha-Amylase gene expression is highly repressed by dietary glucose in Drosophila melanogaster. This glucose effect can be alleviated by exogenous adenosine 3':5'-cyclic monophosphate (cAMP). Here, we show that the relief of glucose repression by cAMP occurs at the level of amylase mRNA abundance. Furthermore, exogenous cAMP was shown to alleviate glucose repression of the transient expression of an amylase gene construct in transformed Amynull larvae. This construct contains only 109 base pairs of the promoter region; this is the minimal length of upstream sequence which is necessary for wild-type levels of amylase gene expression. These results indicate that cis-acting promoter elements located close to the transcriptional start site of the Drosophila amylase gene mediate both glucose repression and the cAMP-derepression effects.", "contents": "Amylase cis-acting sequences mediate the alleviation of glucose repression by cAMP in Drosophila. alpha-Amylase gene expression is highly repressed by dietary glucose in Drosophila melanogaster. This glucose effect can be alleviated by exogenous adenosine 3':5'-cyclic monophosphate (cAMP). Here, we show that the relief of glucose repression by cAMP occurs at the level of amylase mRNA abundance. Furthermore, exogenous cAMP was shown to alleviate glucose repression of the transient expression of an amylase gene construct in transformed Amynull larvae. This construct contains only 109 base pairs of the promoter region; this is the minimal length of upstream sequence which is necessary for wild-type levels of amylase gene expression. These results indicate that cis-acting promoter elements located close to the transcriptional start site of the Drosophila amylase gene mediate both glucose repression and the cAMP-derepression effects."} {"id": "PMID:1282820", "title": "Translation of poly(A)-binding protein mRNA is regulated by growth conditions.", "content": "Translational efficiency of a minor group of mRNAs is regulated by serum levels in 3T6 fibroblasts. Included within this group is the poly(A)-binding protein (PABP) mRNA. We analyzed the distribution of PABP mRNA in polysome profiles and found a large percentage of this mRNA to be translationally repressed in both actively growing (approximately 60%) and resting cells (approximately 70%). Elevated serum levels induced a distinct bimodal distribution of this mRNA between actively translated and repressed fractions. Similarly, treatment of cells with low doses of cycloheximide also generated a partial shift of repressed PABP mRNA into the actively translated fraction. In an attempt to characterize the factors which regulate PABP mRNA translation we have identified the proteins which bind to this mRNA in vitro. Sequences within the 5' untranslated region were found to be sufficient for binding of all proteins to this mRNA. We suggest that this region and the proteins associated with it may be essential for translation control of PABP mRNA.", "contents": "Translation of poly(A)-binding protein mRNA is regulated by growth conditions. Translational efficiency of a minor group of mRNAs is regulated by serum levels in 3T6 fibroblasts. Included within this group is the poly(A)-binding protein (PABP) mRNA. We analyzed the distribution of PABP mRNA in polysome profiles and found a large percentage of this mRNA to be translationally repressed in both actively growing (approximately 60%) and resting cells (approximately 70%). Elevated serum levels induced a distinct bimodal distribution of this mRNA between actively translated and repressed fractions. Similarly, treatment of cells with low doses of cycloheximide also generated a partial shift of repressed PABP mRNA into the actively translated fraction. In an attempt to characterize the factors which regulate PABP mRNA translation we have identified the proteins which bind to this mRNA in vitro. Sequences within the 5' untranslated region were found to be sufficient for binding of all proteins to this mRNA. We suggest that this region and the proteins associated with it may be essential for translation control of PABP mRNA."} {"id": "PMID:1282821", "title": "Variation of nitrogen oxide contents in the streets of Naples.", "content": "Nitrogen oxides were determined in streets of Naples with different density of vehicular traffic. Ventilation allows a dilution of concentration in windy streets but not in protected ones. Streets with a scanty level of vehicular traffic suffer the pollution of contiguous areas. Observed values suggest measures to reduce air pollution.", "contents": "Variation of nitrogen oxide contents in the streets of Naples. Nitrogen oxides were determined in streets of Naples with different density of vehicular traffic. Ventilation allows a dilution of concentration in windy streets but not in protected ones. Streets with a scanty level of vehicular traffic suffer the pollution of contiguous areas. Observed values suggest measures to reduce air pollution."} {"id": "PMID:1282822", "title": "Some gaseous pollutants in the industrial area at east of Naples.", "content": "Nitrogen oxides, ozone, sulphur dioxide and hydrogen sulphide were determined in the industrial area at east of Naples. Emission from vehicular traffic are added to those from fixed sources, but the breeze effect avoids pollution accumulation. Obtained values are low enough if compared with those of other towns.", "contents": "Some gaseous pollutants in the industrial area at east of Naples. Nitrogen oxides, ozone, sulphur dioxide and hydrogen sulphide were determined in the industrial area at east of Naples. Emission from vehicular traffic are added to those from fixed sources, but the breeze effect avoids pollution accumulation. Obtained values are low enough if compared with those of other towns."} {"id": "PMID:1282823", "title": "Neuronal and myogenic muscarinic effects of McN-A-343 on guinea pig longitudinal smooth muscle-myenteric plexus.", "content": "Among muscarinic agonists, the compound McN-A-343, originally proposed as selective stimulant of M1 cholinergic site, was subsequently questioned as a useful pharmacological tool in the classification of muscarinic receptors. In this work, evidence is presented for a dual response of McN-A-343 on longitudinal muscle-myenteric plexus preparation. On electrically-stimulated preparation, this agonist exhibited a pirenzepine-sensitive inhibition of the twitch contractions due to the involvement of neural M1-muscarinic receptor. On the other hand, a direct myogenic contractile action on the unstimulated tissue was observed using McN-A-343 in the same range of concentrations. This latter response, on the basis of the effects of muscarinic and non-muscarinic antagonists tested, seems to involve effectorial muscarinic sites with an unusual mechanism.", "contents": "Neuronal and myogenic muscarinic effects of McN-A-343 on guinea pig longitudinal smooth muscle-myenteric plexus. Among muscarinic agonists, the compound McN-A-343, originally proposed as selective stimulant of M1 cholinergic site, was subsequently questioned as a useful pharmacological tool in the classification of muscarinic receptors. In this work, evidence is presented for a dual response of McN-A-343 on longitudinal muscle-myenteric plexus preparation. On electrically-stimulated preparation, this agonist exhibited a pirenzepine-sensitive inhibition of the twitch contractions due to the involvement of neural M1-muscarinic receptor. On the other hand, a direct myogenic contractile action on the unstimulated tissue was observed using McN-A-343 in the same range of concentrations. This latter response, on the basis of the effects of muscarinic and non-muscarinic antagonists tested, seems to involve effectorial muscarinic sites with an unusual mechanism."} {"id": "PMID:1282824", "title": "Nitric oxide synthase immunoactivity and NADPH diaphorase enzyme activity in neurons of the gastrointestinal tract of the toad, Bufo marinus.", "content": "The presence of nitric oxide synthase (NOS) was demonstrated immunohistochemically, and NADPH diaphorase was demonstrated by enzyme histochemistry in neurons throughout the gastrointestinal tract of the anuran amphibian, Bufo marinus. Successive staining showed that NOS immunoreactivity and NADPH diaphorase activity occurred in precisely the same subgroup of enteric neurons. Subsequent detailed studies of the distribution of these neurons were made using NADPH diaphorase histochemistry. Numerous reactive nerve cell bodies and fibres were found in the myenteric plexus from the esophagus to the cloaca. A dense innervation of the longitudinal and circular muscle layers occurred throughout the gastrointestinal tract. The lamina muscularis mucosae was only prominent in the stomach, where it was sparsely innervated. Reactive nerve cell bodies were common in the submucosa of the large intestine, less common in the small intestine and extremely rare in the stomach and esophagus. Reactive fibres contributed to subepithelial plexuses in the esophagus, colon, rectum and cloaca. It is concluded that NOS/NADPH diaphorase is conserved amongst vertebrate classes and that NO is a likely neurotransmitter in the toad gastrointestinal tract.", "contents": "Nitric oxide synthase immunoactivity and NADPH diaphorase enzyme activity in neurons of the gastrointestinal tract of the toad, Bufo marinus. The presence of nitric oxide synthase (NOS) was demonstrated immunohistochemically, and NADPH diaphorase was demonstrated by enzyme histochemistry in neurons throughout the gastrointestinal tract of the anuran amphibian, Bufo marinus. Successive staining showed that NOS immunoreactivity and NADPH diaphorase activity occurred in precisely the same subgroup of enteric neurons. Subsequent detailed studies of the distribution of these neurons were made using NADPH diaphorase histochemistry. Numerous reactive nerve cell bodies and fibres were found in the myenteric plexus from the esophagus to the cloaca. A dense innervation of the longitudinal and circular muscle layers occurred throughout the gastrointestinal tract. The lamina muscularis mucosae was only prominent in the stomach, where it was sparsely innervated. Reactive nerve cell bodies were common in the submucosa of the large intestine, less common in the small intestine and extremely rare in the stomach and esophagus. Reactive fibres contributed to subepithelial plexuses in the esophagus, colon, rectum and cloaca. It is concluded that NOS/NADPH diaphorase is conserved amongst vertebrate classes and that NO is a likely neurotransmitter in the toad gastrointestinal tract."} {"id": "PMID:1282825", "title": "Low molecular weight proteins in children with renal disease.", "content": "Low molecular weight proteins are of interest in children because their increased urinary excretion is a sign of renal tubular disease and their increased plasma concentration is inversely related to glomerular filtration rate. These proteins include beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and lysozyme. B2M is unstable in acid urine, in contrast to RBP and A1M which are more stable. Any increase in the urinary excretion of B2M or RBP is highly specific for tubular disease, whereas increased excretion of A1M may be seen with glomerular proteinuria. Areas of clinical application include tubular and glomerular diseases, detection of drug toxicity, reflux nephropathy, birth asphyxia and insulin-dependent diabetes mellitus. Methods of sample collection and analysis of these proteins are discussed.", "contents": "Low molecular weight proteins in children with renal disease. Low molecular weight proteins are of interest in children because their increased urinary excretion is a sign of renal tubular disease and their increased plasma concentration is inversely related to glomerular filtration rate. These proteins include beta 2-microglobulin (B2M), retinol-binding protein (RBP), alpha 1-microglobulin (A1M) and lysozyme. B2M is unstable in acid urine, in contrast to RBP and A1M which are more stable. Any increase in the urinary excretion of B2M or RBP is highly specific for tubular disease, whereas increased excretion of A1M may be seen with glomerular proteinuria. Areas of clinical application include tubular and glomerular diseases, detection of drug toxicity, reflux nephropathy, birth asphyxia and insulin-dependent diabetes mellitus. Methods of sample collection and analysis of these proteins are discussed."} {"id": "PMID:1282826", "title": "Lack of transcription and expression of the alpha IIb integrin in human early haematopoietic stem cells.", "content": "The glycoprotein IIb, the alpha subunit of the platelet integrin GPIIb-IIIa, is a marker of megakaryocyte, but the stage of its expression during haematopoiesis remains controversial. We have examined the expression of GPIIb protein and alpha IIb mRNA in early human normal stem cells. We have purified stem cell expressing the CD34 surface marker (CD34+ fraction) and selected among this population quiescent cells (CD34+ MF(R) fraction). We have failed to detect GPIIb protein and alpha IIb mRNA in the pluripotential (CD34+ MF(R)) cells, even with polymerase chain amplification. Therefore alpha IIb transcription and GPIIb protein expression seemed to follow the commitment of the pluripotential cell in the megakaryocyte lineage.", "contents": "Lack of transcription and expression of the alpha IIb integrin in human early haematopoietic stem cells. The glycoprotein IIb, the alpha subunit of the platelet integrin GPIIb-IIIa, is a marker of megakaryocyte, but the stage of its expression during haematopoiesis remains controversial. We have examined the expression of GPIIb protein and alpha IIb mRNA in early human normal stem cells. We have purified stem cell expressing the CD34 surface marker (CD34+ fraction) and selected among this population quiescent cells (CD34+ MF(R) fraction). We have failed to detect GPIIb protein and alpha IIb mRNA in the pluripotential (CD34+ MF(R)) cells, even with polymerase chain amplification. Therefore alpha IIb transcription and GPIIb protein expression seemed to follow the commitment of the pluripotential cell in the megakaryocyte lineage."} {"id": "PMID:1282827", "title": "The production of steel factor mRNA in Diamond-Blackfan anaemia long-term cultures and interactions of steel factor with erythropoietin and interleukin-3.", "content": "Diamond-Blackfan anaemia (DBA) is a congenital macrocytic anaemia. To investigate whether DBA is due to hyporesponsiveness to or hypoproduction of Steel factor (SF), we compared the in vitro responsiveness of the BFU-E contained in the Ficoll-Hypaque non-adherent cell fraction of six DBA marrows with that of four normal marrows and one transient erythroblastopenia of childhood (TEC) marrow. In addition, we studied the effect of soluble SF on long-term marrow cultures (LTMC) and analysed the stromal cells from these cultures for SF mRNA transcripts. All the patients showed an erythropoietin dose-related increase of small BFU-E. The number and size of BFU-E was increased with the addition to the epo of IL-3 or SF; IL-3+SF was not synergistic. The addition of soluble SF to LTMC of DBA patients was associated with a small but consistent increase in non-adherent cell production and an increase in the number of progenitors. Messenger RNA from immortalized stromal cell lines of three patients and from primary bone marrow stromal cells of one patient showed the presence of expected SF transcripts by PCR analysis. These results demonstrate that this group of DBA patients responds to SF and produces SF mRNA normally, indicating that SF itself is not involved in DBA pathophysiology. The effects observed suggest that, despite the lack of evidence for a causative role, SF may prove to be effective treatment for such patients.", "contents": "The production of steel factor mRNA in Diamond-Blackfan anaemia long-term cultures and interactions of steel factor with erythropoietin and interleukin-3. Diamond-Blackfan anaemia (DBA) is a congenital macrocytic anaemia. To investigate whether DBA is due to hyporesponsiveness to or hypoproduction of Steel factor (SF), we compared the in vitro responsiveness of the BFU-E contained in the Ficoll-Hypaque non-adherent cell fraction of six DBA marrows with that of four normal marrows and one transient erythroblastopenia of childhood (TEC) marrow. In addition, we studied the effect of soluble SF on long-term marrow cultures (LTMC) and analysed the stromal cells from these cultures for SF mRNA transcripts. All the patients showed an erythropoietin dose-related increase of small BFU-E. The number and size of BFU-E was increased with the addition to the epo of IL-3 or SF; IL-3+SF was not synergistic. The addition of soluble SF to LTMC of DBA patients was associated with a small but consistent increase in non-adherent cell production and an increase in the number of progenitors. Messenger RNA from immortalized stromal cell lines of three patients and from primary bone marrow stromal cells of one patient showed the presence of expected SF transcripts by PCR analysis. These results demonstrate that this group of DBA patients responds to SF and produces SF mRNA normally, indicating that SF itself is not involved in DBA pathophysiology. The effects observed suggest that, despite the lack of evidence for a causative role, SF may prove to be effective treatment for such patients."} {"id": "PMID:1282828", "title": "Effects of recombinant human granulocyte colony-stimulating factor on neutrophil functions in aged animals.", "content": "We have studied the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on granulopoiesis and neutrophil functions in aged rats and aged mice. We subcutaneously injected rG-CSF or control vehicle into aged rats (22 months old and 25 months old) for 7 consecutive days, counted the peripheral neutrophils and evaluated the functions of neutrophils isolated from venous blood. The peripheral neutrophil count in aged rats tended to be increased as compared with that in young rats (11 weeks old). However, the neutrophils in aged rats exhibited a decline of superoxide anion (O2-) release and phagocytic activity as compared with young rats. The peripheral neutrophil count in aged rats was significantly increased 5-6-fold as many as the control value by rG-CSF treatment, which was accompanied by a significant enhancement of O2- release and of phagocytic activity being restored to normal levels or better. In another series of experiments, we subcutaneously injected rG-CSF or control vehicle into aged mice (24-28 months old) or young mice (8 weeks old) for 7 consecutive days, and evaluated the functions of neutrophils isolated from peritoneal cavity. The peritoneal exudate neutrophils from the aged mice exhibited a decline of phagocytic and chemotactic activity as compared with the young mice. These functions in both young and aged mice were significantly enhanced by rG-CSF-treatment, and these functions in rG-CSF-treated aged mice were restored to a level higher than the level in control young mice. These findings demonstrate that rG-CSF is capable of enhancing granulopoiesis and restoring the age-related decline of neutrophil functions.", "contents": "Effects of recombinant human granulocyte colony-stimulating factor on neutrophil functions in aged animals. We have studied the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on granulopoiesis and neutrophil functions in aged rats and aged mice. We subcutaneously injected rG-CSF or control vehicle into aged rats (22 months old and 25 months old) for 7 consecutive days, counted the peripheral neutrophils and evaluated the functions of neutrophils isolated from venous blood. The peripheral neutrophil count in aged rats tended to be increased as compared with that in young rats (11 weeks old). However, the neutrophils in aged rats exhibited a decline of superoxide anion (O2-) release and phagocytic activity as compared with young rats. The peripheral neutrophil count in aged rats was significantly increased 5-6-fold as many as the control value by rG-CSF treatment, which was accompanied by a significant enhancement of O2- release and of phagocytic activity being restored to normal levels or better. In another series of experiments, we subcutaneously injected rG-CSF or control vehicle into aged mice (24-28 months old) or young mice (8 weeks old) for 7 consecutive days, and evaluated the functions of neutrophils isolated from peritoneal cavity. The peritoneal exudate neutrophils from the aged mice exhibited a decline of phagocytic and chemotactic activity as compared with the young mice. These functions in both young and aged mice were significantly enhanced by rG-CSF-treatment, and these functions in rG-CSF-treated aged mice were restored to a level higher than the level in control young mice. These findings demonstrate that rG-CSF is capable of enhancing granulopoiesis and restoring the age-related decline of neutrophil functions."} {"id": "PMID:1282829", "title": "Adhesion efficiency, platelet density and size.", "content": "We have previously shown that adhesion of human platelets to immobilized collagen is extremely rapid, with initial rates approaching 3% of single particles adhering per 10 ms. Here, we have investigated adhesion efficiency to collagen as a function of platelet density. Platelet subpopulations: low-density (1.040 < d < 1.065 g/ml), intermediate-density (1.065 < d < 1.070 g/ml) and high-density (1.070 < d < 1.080 g/ml) were separated by Percoll density gradient centrifugation. They constituted 24%, 47% and 29% of the total platelet population and had mean volumes of 6.01, 7.37 and 8.21 fl, respectively. Using a continuous-flow, micro-affinity column, we found that the most dense (large) platelets exhibited initial rate of adhesion 4 times greater than the least dense (small) platelets. They were also less sensitive to inhibition by prostacyclin (PGI2). In contrast, there was no significant difference in aggregation induced by high doses of ADP and collagen, indicating that the most dense platelets were not preferentially involved in aggregation induced by high doses of agonists. These results suggest that normal circulating platelets can be distinctly heterogeneous in their ability to adhere to collagen under arterial-flow conditions. The greater efficiency of high-density platelets may be related to increased content of the glycoprotein Ia/IIa (GPIa/IIa) complex.", "contents": "Adhesion efficiency, platelet density and size. We have previously shown that adhesion of human platelets to immobilized collagen is extremely rapid, with initial rates approaching 3% of single particles adhering per 10 ms. Here, we have investigated adhesion efficiency to collagen as a function of platelet density. Platelet subpopulations: low-density (1.040 < d < 1.065 g/ml), intermediate-density (1.065 < d < 1.070 g/ml) and high-density (1.070 < d < 1.080 g/ml) were separated by Percoll density gradient centrifugation. They constituted 24%, 47% and 29% of the total platelet population and had mean volumes of 6.01, 7.37 and 8.21 fl, respectively. Using a continuous-flow, micro-affinity column, we found that the most dense (large) platelets exhibited initial rate of adhesion 4 times greater than the least dense (small) platelets. They were also less sensitive to inhibition by prostacyclin (PGI2). In contrast, there was no significant difference in aggregation induced by high doses of ADP and collagen, indicating that the most dense platelets were not preferentially involved in aggregation induced by high doses of agonists. These results suggest that normal circulating platelets can be distinctly heterogeneous in their ability to adhere to collagen under arterial-flow conditions. The greater efficiency of high-density platelets may be related to increased content of the glycoprotein Ia/IIa (GPIa/IIa) complex."} {"id": "PMID:1282830", "title": "Molecular cloning of monkey liver cytochrome P-450 cDNAs: similarity of the primary sequences to human cytochromes P-450.", "content": "Three cDNAs coding for monkey cytochrome P-450 (P450) 2C, 2E and 3A (MKmp13, MKj1 and MKnf2, respectively) were isolated from a lambda gt11 cDNA library of a liver from a 3-methylcholanthrene (3MC)-treated crab-eating monkey, using cDNA fragments for human P450 2C, 2E and 3A as respective probes. MKmp13 and MKnf2 were 1901 and 2032 bp long, containing entire coding regions for polypeptides of 490 and 503 residues, respectively. The deduced N-terminal amino acid sequences of MKmp13 and MKnf2 were identical with those of P450-MK1 and P450-MK2, which had been purified from liver microsomes of untreated and polychlorinated biphenyl (PCB)-treated crab-eating monkeys, respectively. MKj1 was 1508 bp long, encoding a polypeptide of 449 residues, which is presumed to lack N-terminal 45 residues as compared with the sequence for human P450 2E1. Northern blot analysis indicated that monkey P450 2C, 2E and 3A mRNAs were expressed constitutively in monkey livers. P450 2E and 3A mRNAs were induced by both 3MC and PCB, while P450 2C mRNA was induced only by PCB. The deduced amino acid sequences of four monkey cytochrome P-450 cDNAs, including P450 1A1 (MKah1) which we isolated previously, were more than 92% identical with those of corresponding human cytochrome P-450 cDNAs.", "contents": "Molecular cloning of monkey liver cytochrome P-450 cDNAs: similarity of the primary sequences to human cytochromes P-450. Three cDNAs coding for monkey cytochrome P-450 (P450) 2C, 2E and 3A (MKmp13, MKj1 and MKnf2, respectively) were isolated from a lambda gt11 cDNA library of a liver from a 3-methylcholanthrene (3MC)-treated crab-eating monkey, using cDNA fragments for human P450 2C, 2E and 3A as respective probes. MKmp13 and MKnf2 were 1901 and 2032 bp long, containing entire coding regions for polypeptides of 490 and 503 residues, respectively. The deduced N-terminal amino acid sequences of MKmp13 and MKnf2 were identical with those of P450-MK1 and P450-MK2, which had been purified from liver microsomes of untreated and polychlorinated biphenyl (PCB)-treated crab-eating monkeys, respectively. MKj1 was 1508 bp long, encoding a polypeptide of 449 residues, which is presumed to lack N-terminal 45 residues as compared with the sequence for human P450 2E1. Northern blot analysis indicated that monkey P450 2C, 2E and 3A mRNAs were expressed constitutively in monkey livers. P450 2E and 3A mRNAs were induced by both 3MC and PCB, while P450 2C mRNA was induced only by PCB. The deduced amino acid sequences of four monkey cytochrome P-450 cDNAs, including P450 1A1 (MKah1) which we isolated previously, were more than 92% identical with those of corresponding human cytochrome P-450 cDNAs."} {"id": "PMID:1282831", "title": "Expression of vascular cell adhesion molecule-1 in human renal allografts.", "content": "The expression of vascular cell adhesion molecule-1 (VCAM-1) in 11 human renal allograft biopsies and 3 normal kidney specimens was investigated by immunocytochemistry. VCAM-1 expression was correlated with the degree of CD3+ T cell infiltration and the clinicopathologic diagnosis of acute rejection. CD3+ infiltrates were seen in all biopsies with rejection, but not in normal biopsies or one with acute tubular necrosis, and were accompanied by CD68+ monocyte/macrophage infiltrates. In normal biopsies, VCAM-1 was present on occasional tubules, where its expression was patchy and restricted to the basolateral surface of cells with slight cytoplasmic staining. The total number of tubules expressing VCAM-1 significantly increased in specimens infiltrated with CD3+ T cells. Moreover, in these infiltrated biopsy specimens, VCAM-1 was present throughout the cytoplasm of tubular cells concentrated on the basolateral surface. VCAM-1 was also observed on vascular endothelial cells where its expression correlated with the degree of CD3+ infiltrate. Mean scores (0 to 3+) for endothelial VCAM-1 expression increased from 0 (CD3+ score, 0) to a mean score of 2.25 in association with CD3+ T cell infiltrates (CD3+ score, 3). Endothelial VCAM-1 was predominantly on vessels in areas of infiltrate, including peritubular capillaries, venules, and arterioles, but was notably absent on glomerular endothelium. VCAM-1 also stained mesangial cells in an occasional CD3+ infiltrated specimen. It was concluded that the expression of VCAM-1 is increased on renal tubules and renovascular endothelium in rejecting renal allografts in association with CD3+ infiltrates.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Expression of vascular cell adhesion molecule-1 in human renal allografts. The expression of vascular cell adhesion molecule-1 (VCAM-1) in 11 human renal allograft biopsies and 3 normal kidney specimens was investigated by immunocytochemistry. VCAM-1 expression was correlated with the degree of CD3+ T cell infiltration and the clinicopathologic diagnosis of acute rejection. CD3+ infiltrates were seen in all biopsies with rejection, but not in normal biopsies or one with acute tubular necrosis, and were accompanied by CD68+ monocyte/macrophage infiltrates. In normal biopsies, VCAM-1 was present on occasional tubules, where its expression was patchy and restricted to the basolateral surface of cells with slight cytoplasmic staining. The total number of tubules expressing VCAM-1 significantly increased in specimens infiltrated with CD3+ T cells. Moreover, in these infiltrated biopsy specimens, VCAM-1 was present throughout the cytoplasm of tubular cells concentrated on the basolateral surface. VCAM-1 was also observed on vascular endothelial cells where its expression correlated with the degree of CD3+ infiltrate. Mean scores (0 to 3+) for endothelial VCAM-1 expression increased from 0 (CD3+ score, 0) to a mean score of 2.25 in association with CD3+ T cell infiltrates (CD3+ score, 3). Endothelial VCAM-1 was predominantly on vessels in areas of infiltrate, including peritubular capillaries, venules, and arterioles, but was notably absent on glomerular endothelium. VCAM-1 also stained mesangial cells in an occasional CD3+ infiltrated specimen. It was concluded that the expression of VCAM-1 is increased on renal tubules and renovascular endothelium in rejecting renal allografts in association with CD3+ infiltrates.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282832", "title": "Stratified organization of the nicotinic acetylcholine receptor channel.", "content": "Mutations of leucine 247 within the M2 channel domain of the alpha 7 neuronal nicotinic receptor, confer electrophysiological and pharmacological properties, which allow one of the desensitized states to become conductive. Here we show that, in Xenopus oocytes, the effects of the mutations were preserved when 1,2-bis(2-aminophenoxy)-ethane N,N,N',N'-tetraacetic acid (BAPTA) was injected in the cytoplasm to block Ca(2+)-dependent chloride currents, and that in agreement with the proposed interpretation, the ionic currents do not desensitize and rise slowly, in the time-scale of seconds, upon agonist application. Interestingly, similar effects were observed when the two rings (T244, V251) neighbouring L247 on the alpha-helix, but not the more distant ones (S240, L254/255), were mutated, thus supporting the proposal of a functional stratification of the channel domain.", "contents": "Stratified organization of the nicotinic acetylcholine receptor channel. Mutations of leucine 247 within the M2 channel domain of the alpha 7 neuronal nicotinic receptor, confer electrophysiological and pharmacological properties, which allow one of the desensitized states to become conductive. Here we show that, in Xenopus oocytes, the effects of the mutations were preserved when 1,2-bis(2-aminophenoxy)-ethane N,N,N',N'-tetraacetic acid (BAPTA) was injected in the cytoplasm to block Ca(2+)-dependent chloride currents, and that in agreement with the proposed interpretation, the ionic currents do not desensitize and rise slowly, in the time-scale of seconds, upon agonist application. Interestingly, similar effects were observed when the two rings (T244, V251) neighbouring L247 on the alpha-helix, but not the more distant ones (S240, L254/255), were mutated, thus supporting the proposal of a functional stratification of the channel domain."} {"id": "PMID:1282833", "title": "Age-related changes in galanin- and calretinin-immunoreactive nerves of guinea-pig gallbladder.", "content": "Age-related changes in the expression of galanin- and calretinin-like immunoreactivity in the ganglionated plexus of 2-4 day, 6 month and 2 year old guinea-pig gallbladder were investigated. The ganglionated plexus was studied using immunohistochemical labelling techniques on whole mount stretch preparations of the gallbladders. Galanin- and calretinin-like immunoreactivity did not differ significantly between age groups of the 2-4 day and 6 month olds except for some reduction of calretinin-immunofluorescent nerves in the 6 month old preparations. However, in the ganglionated plexus of the 2 year old guinea-pig gallbladders, neither galanin- nor calretinin-like immunoreactivity could be detected. The implication of these findings, in relation to the physiological activity of the gallbladder is discussed.", "contents": "Age-related changes in galanin- and calretinin-immunoreactive nerves of guinea-pig gallbladder. Age-related changes in the expression of galanin- and calretinin-like immunoreactivity in the ganglionated plexus of 2-4 day, 6 month and 2 year old guinea-pig gallbladder were investigated. The ganglionated plexus was studied using immunohistochemical labelling techniques on whole mount stretch preparations of the gallbladders. Galanin- and calretinin-like immunoreactivity did not differ significantly between age groups of the 2-4 day and 6 month olds except for some reduction of calretinin-immunofluorescent nerves in the 6 month old preparations. However, in the ganglionated plexus of the 2 year old guinea-pig gallbladders, neither galanin- nor calretinin-like immunoreactivity could be detected. The implication of these findings, in relation to the physiological activity of the gallbladder is discussed."} {"id": "PMID:1282834", "title": "Differential expression of acidic and basic FGF in the rat substantia nigra during development.", "content": "Both acidic (aFGF) and basic (bFGF) fibroblast growth factors have been shown to be present in the adult rat ventral mesencephalon and to exert effects on cultured mesencephalic cells. In the present study we have examined the expression of aFGF and bFGF in the rat ventral mesencephalon at various stages of development. bFGF was present at all ages examined [embryonic day 16 (E16) to postnatal day 90 (P90)]. In contrast, aFGF was not detectable at embryonic and early postnatal ages, but was observed at later (P20, P60, P90) postnatal stages. These data suggest that aFGF and bFGF may have functions in mesencephalic dopamine neurones in different stages of development.", "contents": "Differential expression of acidic and basic FGF in the rat substantia nigra during development. Both acidic (aFGF) and basic (bFGF) fibroblast growth factors have been shown to be present in the adult rat ventral mesencephalon and to exert effects on cultured mesencephalic cells. In the present study we have examined the expression of aFGF and bFGF in the rat ventral mesencephalon at various stages of development. bFGF was present at all ages examined [embryonic day 16 (E16) to postnatal day 90 (P90)]. In contrast, aFGF was not detectable at embryonic and early postnatal ages, but was observed at later (P20, P60, P90) postnatal stages. These data suggest that aFGF and bFGF may have functions in mesencephalic dopamine neurones in different stages of development."} {"id": "PMID:1282837", "title": "Computers in medicine: enhancing medical care for children with developmental disabilities.", "content": "Caring for children with developmental disabilities and their families requires the close monitoring and management of a multitude of complex medical and psychosocial issues. The need for an interdisciplinary team approach to address these concerns presents special logistical problems on how to organize and present the information obtained during a clinic visit, and how to expedite the dissemination of this information to the team members. I am currently utilizing a computerized medical record database in the Developmental Disabilities Clinic at Children's Hospital-Columbus, Ohio and at The Nisonger Center a university affiliated program (UAP). The hardware required for the operation of this system includes a Macintosh PowerBook 170 and FilemakerPro software by Claris. The flexibility of use and the potential future applications of this program provides a practical clinical approach to caring for children with developmental disabilities.", "contents": "Computers in medicine: enhancing medical care for children with developmental disabilities. Caring for children with developmental disabilities and their families requires the close monitoring and management of a multitude of complex medical and psychosocial issues. The need for an interdisciplinary team approach to address these concerns presents special logistical problems on how to organize and present the information obtained during a clinic visit, and how to expedite the dissemination of this information to the team members. I am currently utilizing a computerized medical record database in the Developmental Disabilities Clinic at Children's Hospital-Columbus, Ohio and at The Nisonger Center a university affiliated program (UAP). The hardware required for the operation of this system includes a Macintosh PowerBook 170 and FilemakerPro software by Claris. The flexibility of use and the potential future applications of this program provides a practical clinical approach to caring for children with developmental disabilities."} {"id": "PMID:1282835", "title": "Preretinal neovascularization in diabetic retinopathy: a preliminary investigation using contrast-enhanced magnetic resonance imaging.", "content": "Preretinal neovascularization is a well-described feature of advanced diabetic retinopathy. In this study, contrast-enhanced magnetic resonance imaging was used to examine blood-retinal barrier breakdown associated with preretinal neovascularization in three subjects with proliferative diabetic retinopathy. Using a standard imaging protocol, a varying degree of vitreous enhancement was observed in these eyes. The location and severity of enhancement, judged by visual inspection of the images, corresponded to the fluorescein angiographic and/or clinical appearance of preretinal neovascularization. This result suggests that contrast-enhanced magnetic resonance imaging may prove a reasonable approach to the identification of preretinal neovascularization in eyes with significant media opacities.", "contents": "Preretinal neovascularization in diabetic retinopathy: a preliminary investigation using contrast-enhanced magnetic resonance imaging. Preretinal neovascularization is a well-described feature of advanced diabetic retinopathy. In this study, contrast-enhanced magnetic resonance imaging was used to examine blood-retinal barrier breakdown associated with preretinal neovascularization in three subjects with proliferative diabetic retinopathy. Using a standard imaging protocol, a varying degree of vitreous enhancement was observed in these eyes. The location and severity of enhancement, judged by visual inspection of the images, corresponded to the fluorescein angiographic and/or clinical appearance of preretinal neovascularization. This result suggests that contrast-enhanced magnetic resonance imaging may prove a reasonable approach to the identification of preretinal neovascularization in eyes with significant media opacities."} {"id": "PMID:1282838", "title": "Effects of selenium on ribonucleic acid synthesis and degradation in rat liver.", "content": "Six groups of weanling rats were fed a low-selenium based diet containing less than 0.01 mg/kg of Se in the diet or the basal diet supplemented with five levels of selenium as selenite (0.1, 0.2, 0.3, 0.4 and 0.5 mg/kg) for at least 16 to 18 weeks. For determination of the effect of selenium on ribonucleic acid (RNA) synthesis in rat liver, rats of each dietary group were injected with a single dose of (5-3H)-uridine, and 3 hours later their livers were removed and subjected to cell fractionation. The radioactivities in the nuclear and cytoplasmic RNA were taken as a measure of the RNA synthesis rate. With selenium supplementation between 0.2 and 0.5 mg/kg diet, the radioactivities, amounts of RNA, as well as RNA/DNA ratios in both nuclear and cytoplasmic fractions of rat liver all increased significantly. In addition, at similar levels of selenium supplementation, statistically significant increments of glutathione peroxidase (GSH-Px) activity and reductions in lipid peroxide in liver were also observed. For assessment of RNA degradation, activities of ribonucleases (RNase) and RNase inhibitor in rats fed the low-selenium diet or a selenium-supplemented diet were determined. The activities of acid RNase and both free and latent alkaline RNase in liver homogenate were not affected by selenium deficiency; however, the level of RNase inhibitor present in the supernatant fraction increased significantly with selenium supplementation at 0.2 mg/kg diet.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of selenium on ribonucleic acid synthesis and degradation in rat liver. Six groups of weanling rats were fed a low-selenium based diet containing less than 0.01 mg/kg of Se in the diet or the basal diet supplemented with five levels of selenium as selenite (0.1, 0.2, 0.3, 0.4 and 0.5 mg/kg) for at least 16 to 18 weeks. For determination of the effect of selenium on ribonucleic acid (RNA) synthesis in rat liver, rats of each dietary group were injected with a single dose of (5-3H)-uridine, and 3 hours later their livers were removed and subjected to cell fractionation. The radioactivities in the nuclear and cytoplasmic RNA were taken as a measure of the RNA synthesis rate. With selenium supplementation between 0.2 and 0.5 mg/kg diet, the radioactivities, amounts of RNA, as well as RNA/DNA ratios in both nuclear and cytoplasmic fractions of rat liver all increased significantly. In addition, at similar levels of selenium supplementation, statistically significant increments of glutathione peroxidase (GSH-Px) activity and reductions in lipid peroxide in liver were also observed. For assessment of RNA degradation, activities of ribonucleases (RNase) and RNase inhibitor in rats fed the low-selenium diet or a selenium-supplemented diet were determined. The activities of acid RNase and both free and latent alkaline RNase in liver homogenate were not affected by selenium deficiency; however, the level of RNase inhibitor present in the supernatant fraction increased significantly with selenium supplementation at 0.2 mg/kg diet.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282839", "title": "Changes in zinc metabolism after burns: observations, explanations, clinical implications.", "content": "Zinc in plasma and urine and serum albumin and alpha 2-macroglobulin were measured in 48 patients with burns. Mean total burned surface area amounted to 18%, ranging from 2 to 55%, and mean hospitalization time amounted to 35 days, ranging from 10 to 124 days. All parameters showed a decrease during the first two post-burn days. Minimal values were reached on days 2 and 3 for plasma and urine zinc, and between days 5 and 10 for the proteins. Thereafter, values increased, rapidly for both plasma and urinary zinc, more slowly for albumin and alpha 2-macroglobulin. The ratio R of the total plasma zinc minus the alpha 2-macroglobulin concentration to the albumin concentration is postulated as an indicator for zinc deficiency. From values of R and of the urinary zinc excretion, conclusions can be drawn about various processes of the zinc metabolism that may occur during the acute stage following the thermal accident and during the stages of tissue demarcation and of recovery. These processes are discussed in terms of possible temporary and/or local zinc deficiency. Evidence is presented that zinc administration in only indicated during the final stages of recovery in case of inadequate dietary intake.", "contents": "Changes in zinc metabolism after burns: observations, explanations, clinical implications. Zinc in plasma and urine and serum albumin and alpha 2-macroglobulin were measured in 48 patients with burns. Mean total burned surface area amounted to 18%, ranging from 2 to 55%, and mean hospitalization time amounted to 35 days, ranging from 10 to 124 days. All parameters showed a decrease during the first two post-burn days. Minimal values were reached on days 2 and 3 for plasma and urine zinc, and between days 5 and 10 for the proteins. Thereafter, values increased, rapidly for both plasma and urinary zinc, more slowly for albumin and alpha 2-macroglobulin. The ratio R of the total plasma zinc minus the alpha 2-macroglobulin concentration to the albumin concentration is postulated as an indicator for zinc deficiency. From values of R and of the urinary zinc excretion, conclusions can be drawn about various processes of the zinc metabolism that may occur during the acute stage following the thermal accident and during the stages of tissue demarcation and of recovery. These processes are discussed in terms of possible temporary and/or local zinc deficiency. Evidence is presented that zinc administration in only indicated during the final stages of recovery in case of inadequate dietary intake."} {"id": "PMID:1282840", "title": "Comparison of the antigenic and allergenic properties of three types of bovine epithelial material.", "content": "The antigenic and allergenic characteristics of three bovine epithelial extracts, dander, skin scrapings and whole skin, were compared using IgE-ELISA inhibition and SDS-PAGE with immunoblotting. Cow dander extract was shown to contain more allergenic activity than skin scrapings or whole skin extracts which were needed in about three times higher amounts than cow dander extract to induce the same degree of inhibition in ELISA. Skin scrapings and whole skin extracts contained more high-molecular weight components than dander extract. These components were at least partly serum-derived and reacted often with the IgG but not with the IgE of both the cow-asthmatics and their control subjects. The antigenic characteristics of the low-molecular weight components as well as the allergenic qualities of these three epithelial preparations were generally similar. Using the sera of 49 cow-asthmatic farmers, two major allergens were detected at 20 and 22 kD in all three extracts. Our results show that the highest amount of allergenic material and all the essential allergens are present in cow dander extract. In addition, the normally non-allergenic high molecular weight components are detected in low concentrations in dander extract. Therefore it is concluded that cow dander extract is the best alternative for allergen purification and allergen extract preparation.", "contents": "Comparison of the antigenic and allergenic properties of three types of bovine epithelial material. The antigenic and allergenic characteristics of three bovine epithelial extracts, dander, skin scrapings and whole skin, were compared using IgE-ELISA inhibition and SDS-PAGE with immunoblotting. Cow dander extract was shown to contain more allergenic activity than skin scrapings or whole skin extracts which were needed in about three times higher amounts than cow dander extract to induce the same degree of inhibition in ELISA. Skin scrapings and whole skin extracts contained more high-molecular weight components than dander extract. These components were at least partly serum-derived and reacted often with the IgG but not with the IgE of both the cow-asthmatics and their control subjects. The antigenic characteristics of the low-molecular weight components as well as the allergenic qualities of these three epithelial preparations were generally similar. Using the sera of 49 cow-asthmatic farmers, two major allergens were detected at 20 and 22 kD in all three extracts. Our results show that the highest amount of allergenic material and all the essential allergens are present in cow dander extract. In addition, the normally non-allergenic high molecular weight components are detected in low concentrations in dander extract. Therefore it is concluded that cow dander extract is the best alternative for allergen purification and allergen extract preparation."} {"id": "PMID:1282841", "title": "The effect of mast cell chymase on extracellular matrix: studies in autoimmune thyroiditis and in cultured thyroid cells.", "content": "In the first part of the study we analyzed the morphology of mast cells in autoimmune thyroiditis of BB/W rats. In the early stage of thyroiditis mast cells showed exocytosis of granules into the interstitium; this was associated with disorganization of the extracellular matrix and the appearance of a translucent ground substance in stroma. Mast cells were not seen in the mononuclear infiltrates in the later stages of thyroiditis. In order to further study the effect of mast cells on the extracellular matrix, we evaluated the effect of mast cell lysate and purified chymase on the matrix of cultured thyroid cells. Mast cells were obtained from peritoneal cavity; mast cell chymase was purified by anion exchange chromatography. After exposure to chymase there was a reduction of pericellular fibronectin in cultured thyroid cells, while laminin in matrix remained unchanged. Similarly, as found by gel electrophoresis, soluble fibronectin and vitronectin were digested by chymase in the reaction mixture. Cell attachment on both fibronectin and vitronectin was significantly decreased upon exposure of matrix proteins to chymase. The effects of chymase were abolished by enzyme inhibitor phenylmethane sulfonyl fluoride. These data suggest that mast cells possess proteolytic enzymes capable of digesting different host proteins which may have a role in the thyroid cell interaction with the surrounding matrix.", "contents": "The effect of mast cell chymase on extracellular matrix: studies in autoimmune thyroiditis and in cultured thyroid cells. In the first part of the study we analyzed the morphology of mast cells in autoimmune thyroiditis of BB/W rats. In the early stage of thyroiditis mast cells showed exocytosis of granules into the interstitium; this was associated with disorganization of the extracellular matrix and the appearance of a translucent ground substance in stroma. Mast cells were not seen in the mononuclear infiltrates in the later stages of thyroiditis. In order to further study the effect of mast cells on the extracellular matrix, we evaluated the effect of mast cell lysate and purified chymase on the matrix of cultured thyroid cells. Mast cells were obtained from peritoneal cavity; mast cell chymase was purified by anion exchange chromatography. After exposure to chymase there was a reduction of pericellular fibronectin in cultured thyroid cells, while laminin in matrix remained unchanged. Similarly, as found by gel electrophoresis, soluble fibronectin and vitronectin were digested by chymase in the reaction mixture. Cell attachment on both fibronectin and vitronectin was significantly decreased upon exposure of matrix proteins to chymase. The effects of chymase were abolished by enzyme inhibitor phenylmethane sulfonyl fluoride. These data suggest that mast cells possess proteolytic enzymes capable of digesting different host proteins which may have a role in the thyroid cell interaction with the surrounding matrix."} {"id": "PMID:1282842", "title": "Comparison of methods of production of farmer's lung antigens.", "content": "The extracellular growth products of Micropolyspora faeni, Thermoactinomyces vulgaris and Thermoactinomyces candidus were prepared by three methods; (1) double dialysis; (2) growth in tryptone soya broth (TSB) and (3) synthetic broth (AOAC). It was found that double dialysis was superior to growth in TSB or AOAC for the production of M. faeni antigens, as determined by immunoblot. Double dialysis, TSB and AOAC were similar for antigens of T. vulgaris and T. candidus. Both organisms showed bands of the same mobility on immunoblot and also produced lines of identity on double diffusion.", "contents": "Comparison of methods of production of farmer's lung antigens. The extracellular growth products of Micropolyspora faeni, Thermoactinomyces vulgaris and Thermoactinomyces candidus were prepared by three methods; (1) double dialysis; (2) growth in tryptone soya broth (TSB) and (3) synthetic broth (AOAC). It was found that double dialysis was superior to growth in TSB or AOAC for the production of M. faeni antigens, as determined by immunoblot. Double dialysis, TSB and AOAC were similar for antigens of T. vulgaris and T. candidus. Both organisms showed bands of the same mobility on immunoblot and also produced lines of identity on double diffusion."} {"id": "PMID:1282843", "title": "Structure of the major cat allergen Fel d I in different allergen sources: an immunoblotting analysis with monoclonal antibodies against denatured Fel d I and human IgE.", "content": "In this paper we show the reactivity of monoclonal antibodies (mAbs) and human IgE with Fel d I from different allergen sources in reduced SDS-PAGE immunoblots. By SDS-PAGE analysis of affinity-purified 125I-Fel d I, a 14- to 20-kD band was found, which dissociated under reducing conditions into a 4- to 5-kD chain (chain 1) and a 11- to 15-kD chain (chain 2). In initial immunoblotting experiments with mAbs against Fel d I however, only chain 1 was detected, while the mAbs lost activity upon reduction of Fel d I. Therefore mAbs were raised against reduced and alkylated Fel d I. Two of the four mAbs to 'denatured' Fel d I that were obtained did react with chain 2 on an immunoblot under reducing conditions; the other two reacted with chain 1. The mAbs did not react with native Fel d I. With these mAbs and human IgE, differences between allergen source materials in blot patterns of Fel d I were detected. A variable molecular weight for the protein stained with mAb antichain 2 was found, and occasionally the presence of a 12-kD band stained with mAb antichain 1. Human IgE strongly bound to chain 1 of Fel d I, while only 2 out of 6 sera gave a strong reaction with chain 2. The additional 12-kD band was also recognized by human IgE. In a competitive radioimmunoassay with mAb antichain 1, differences in levels of 'denatured' Fel d I between commercial extracts were quantitated. In vitro 'denatured' Fel d I was generated under high pH conditions. The reactivity of human IgE with this 'denatured' Fel d I was demonstrated in indirect RAST experiments with mAb antichain 1. We conclude that mAb antichain 1 recognizes a form of Fel d I that is not detected by mAb antinative Fel d I, but does react with human IgE.", "contents": "Structure of the major cat allergen Fel d I in different allergen sources: an immunoblotting analysis with monoclonal antibodies against denatured Fel d I and human IgE. In this paper we show the reactivity of monoclonal antibodies (mAbs) and human IgE with Fel d I from different allergen sources in reduced SDS-PAGE immunoblots. By SDS-PAGE analysis of affinity-purified 125I-Fel d I, a 14- to 20-kD band was found, which dissociated under reducing conditions into a 4- to 5-kD chain (chain 1) and a 11- to 15-kD chain (chain 2). In initial immunoblotting experiments with mAbs against Fel d I however, only chain 1 was detected, while the mAbs lost activity upon reduction of Fel d I. Therefore mAbs were raised against reduced and alkylated Fel d I. Two of the four mAbs to 'denatured' Fel d I that were obtained did react with chain 2 on an immunoblot under reducing conditions; the other two reacted with chain 1. The mAbs did not react with native Fel d I. With these mAbs and human IgE, differences between allergen source materials in blot patterns of Fel d I were detected. A variable molecular weight for the protein stained with mAb antichain 2 was found, and occasionally the presence of a 12-kD band stained with mAb antichain 1. Human IgE strongly bound to chain 1 of Fel d I, while only 2 out of 6 sera gave a strong reaction with chain 2. The additional 12-kD band was also recognized by human IgE. In a competitive radioimmunoassay with mAb antichain 1, differences in levels of 'denatured' Fel d I between commercial extracts were quantitated. In vitro 'denatured' Fel d I was generated under high pH conditions. The reactivity of human IgE with this 'denatured' Fel d I was demonstrated in indirect RAST experiments with mAb antichain 1. We conclude that mAb antichain 1 recognizes a form of Fel d I that is not detected by mAb antinative Fel d I, but does react with human IgE."} {"id": "PMID:1282844", "title": "Chondroitin sulfate proteoglycan expression during neuronal development.", "content": "Proteoglycans of developing chick brain were distinguished on the basis of reactivity with four well characterized antibody reagents (S103L, to the CS-rich domain; HNK-1, to 6-sulfated glucuronic acid; 1-C-3, to the HABr region and 5-D-4, to KS chains). One chondroitin sulfate proteoglycan reacted exclusively with S103L and 1-C-3 and not with the other two antibodies, hence is designated the S103L reactive brain CSPG. The other proteoglycan reacted exclusively with HNK-1 and 5-D-4 and not with S103L and 1-C-3, hence it is designated the HNK-1 reactive brain CSPG. In addition to these immunological distinctions, the S103L and HNK-1 CSPGs exhibited significant biochemical differences at both the protein and carbohydrate levels. Most interestingly, both CSPGs were found in all regions of the brain, and were expressed in a developmentally regulated pattern. The S103L CSPG was not detectable prior to embryonic day 7, increased to a maximum at day 13-15 and declined by day 20 in most brain regions examined. In contrast, the HNK-1 CSPG was present as early as embryonic day 4 and remained constant through hatching. Neuronal cultures established from embryonic day 6 (E6) cerebral hemispheres represent an in vitro paradigm that mimics in vivo neuronal development and differentiation. In this culture system we found that the expression of the S103L and HNK-1 CSPG followed a pattern similar to that observed in developing brain and further, that neurons are probably the sole source of S103L CSPG in cerebral cortex during neuroembryogenesis.", "contents": "Chondroitin sulfate proteoglycan expression during neuronal development. Proteoglycans of developing chick brain were distinguished on the basis of reactivity with four well characterized antibody reagents (S103L, to the CS-rich domain; HNK-1, to 6-sulfated glucuronic acid; 1-C-3, to the HABr region and 5-D-4, to KS chains). One chondroitin sulfate proteoglycan reacted exclusively with S103L and 1-C-3 and not with the other two antibodies, hence is designated the S103L reactive brain CSPG. The other proteoglycan reacted exclusively with HNK-1 and 5-D-4 and not with S103L and 1-C-3, hence it is designated the HNK-1 reactive brain CSPG. In addition to these immunological distinctions, the S103L and HNK-1 CSPGs exhibited significant biochemical differences at both the protein and carbohydrate levels. Most interestingly, both CSPGs were found in all regions of the brain, and were expressed in a developmentally regulated pattern. The S103L CSPG was not detectable prior to embryonic day 7, increased to a maximum at day 13-15 and declined by day 20 in most brain regions examined. In contrast, the HNK-1 CSPG was present as early as embryonic day 4 and remained constant through hatching. Neuronal cultures established from embryonic day 6 (E6) cerebral hemispheres represent an in vitro paradigm that mimics in vivo neuronal development and differentiation. In this culture system we found that the expression of the S103L and HNK-1 CSPG followed a pattern similar to that observed in developing brain and further, that neurons are probably the sole source of S103L CSPG in cerebral cortex during neuroembryogenesis."} {"id": "PMID:1282845", "title": "Does a cytoplasmic bridge connect the CNS axon with the inner loop of myelin?", "content": "Sarah Luse (1959) reported over 30 years ago on the presence of a bridge connecting the axon to the myelin sheath in the central nervous system (CNS). This notion has not been accepted in the literature. Wolman (1992) found that the progress of demyelination in some viral diseases affecting the CNS fits the concept of Luse, as the process occurred primarily along the major dense line of myelin, which is in continuity with the cytoplasm of the oligodendroglial cell. Injection of Lucifer yellow (LY) and horseradish peroxidase (HRP) into the vitreous of guinea pigs, with and without iontophoresis, resulted in labeling of the nerve axons and myelin. Labeling of myelin by HRP occurred along the major dense line which indicated that a transient or permanent cytoplasmic bridge connects axons and myelin in the optic nerve.", "contents": "Does a cytoplasmic bridge connect the CNS axon with the inner loop of myelin? Sarah Luse (1959) reported over 30 years ago on the presence of a bridge connecting the axon to the myelin sheath in the central nervous system (CNS). This notion has not been accepted in the literature. Wolman (1992) found that the progress of demyelination in some viral diseases affecting the CNS fits the concept of Luse, as the process occurred primarily along the major dense line of myelin, which is in continuity with the cytoplasm of the oligodendroglial cell. Injection of Lucifer yellow (LY) and horseradish peroxidase (HRP) into the vitreous of guinea pigs, with and without iontophoresis, resulted in labeling of the nerve axons and myelin. Labeling of myelin by HRP occurred along the major dense line which indicated that a transient or permanent cytoplasmic bridge connects axons and myelin in the optic nerve."} {"id": "PMID:1282846", "title": "Subtype of muscarinic receptor coupled to the attenuation of hormone-stimulated cAMP accumulation in NG108-15 neuroblastoma x glioma hybrid cells.", "content": "The subtype of muscarinic receptor which mediates cAMP attenuation is not established. Therefore, several selective muscarinic antagonists were used to characterize the subtype of muscarinic receptor coupled to the inhibition of hormone-stimulated cAMP accumulation using NG108-15 neuroblastoma x glioma hybrid cells. These cells were prelabeled with [2-3H]-adenine, washed, and resuspended in a culture medium containing the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM). The labeled cells were preincubated with the different antagonists 12-15 min. before they were challenged with agonists. The formation of [3H]-cAMP was activated by PGE1 (1 microM) or forskolin (1 microM). In all cases, [3H]-cAMP formed was separated and measured. Carbachol (100 microM) and McN-A343 (10 mM) were used as standard muscarinic agonists. These studies gave the following results: a) McN-A343 (10 mM), an M1 receptor agonist, was only a partial agonist causing 40% inhibition of cAMP accumulation indicating that this effect was not mediated by an M1 receptor; b) The M1-selective antagonist, pirenzepine, exhibited low affinity (pA2 6.2) further suggesting that an M1 receptor was not coupled to the attenuation of cAMP accumulation; c) Two selective M2 antagonists (AF-DX 116 and methoctramine) and M3 antagonist (HHSiD) were used to further characterize these muscarinic receptors. The order of all antagonists based on their affinities (pA2 values) could be arranged in the following order: atropine (9.0) > methoctramine (7.6) > HHSiD (6.9) > AF-DX 116 (6.6) > pirenzepine (6.2). HHSiD exhibits the same degree of affinity to M2 receptors of other tissues as it does to those of NG cells.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Subtype of muscarinic receptor coupled to the attenuation of hormone-stimulated cAMP accumulation in NG108-15 neuroblastoma x glioma hybrid cells. The subtype of muscarinic receptor which mediates cAMP attenuation is not established. Therefore, several selective muscarinic antagonists were used to characterize the subtype of muscarinic receptor coupled to the inhibition of hormone-stimulated cAMP accumulation using NG108-15 neuroblastoma x glioma hybrid cells. These cells were prelabeled with [2-3H]-adenine, washed, and resuspended in a culture medium containing the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.5 mM). The labeled cells were preincubated with the different antagonists 12-15 min. before they were challenged with agonists. The formation of [3H]-cAMP was activated by PGE1 (1 microM) or forskolin (1 microM). In all cases, [3H]-cAMP formed was separated and measured. Carbachol (100 microM) and McN-A343 (10 mM) were used as standard muscarinic agonists. These studies gave the following results: a) McN-A343 (10 mM), an M1 receptor agonist, was only a partial agonist causing 40% inhibition of cAMP accumulation indicating that this effect was not mediated by an M1 receptor; b) The M1-selective antagonist, pirenzepine, exhibited low affinity (pA2 6.2) further suggesting that an M1 receptor was not coupled to the attenuation of cAMP accumulation; c) Two selective M2 antagonists (AF-DX 116 and methoctramine) and M3 antagonist (HHSiD) were used to further characterize these muscarinic receptors. The order of all antagonists based on their affinities (pA2 values) could be arranged in the following order: atropine (9.0) > methoctramine (7.6) > HHSiD (6.9) > AF-DX 116 (6.6) > pirenzepine (6.2). HHSiD exhibits the same degree of affinity to M2 receptors of other tissues as it does to those of NG cells.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282850", "title": "Treating hopelessness: nursing strategies from six countries.", "content": "Strategies to treat hopelessness were described by 188 critical care nurses from Belgium, Canada, Colombia, England, France, and the United States. Data were collected by an open-ended questionnaire distributed by site coordinators to 50 randomly selected critical care nurses in one or more hospitals in each of the six countries. Data were analyzed using content analysis and data reduction techniques. Prior to collapsing data into hope-inspiring categories, discrete words or phrases to treat hopelessness were enumerated for each country. Interrater consensus was reached on each category label. Hope-inspiring strategies included use of interpersonal self (listening, presence, empathy, directing the interaction away from hopelessness themes); involvement and caring for the family; sharing success stories; use of progress reports; empowerment; and referral to experts (psychologists, clinical nurse specialists). Differences were evident among the countries. Providing physical comfort was emphasized by Belgium, Colombia, and Canada but not mentioned by other countries. Nurses from France used strategies labeled \"positive provocation\" to keep patients self-sufficient, autonomous, and able to move beyond dwelling on hopelessness.", "contents": "Treating hopelessness: nursing strategies from six countries. Strategies to treat hopelessness were described by 188 critical care nurses from Belgium, Canada, Colombia, England, France, and the United States. Data were collected by an open-ended questionnaire distributed by site coordinators to 50 randomly selected critical care nurses in one or more hospitals in each of the six countries. Data were analyzed using content analysis and data reduction techniques. Prior to collapsing data into hope-inspiring categories, discrete words or phrases to treat hopelessness were enumerated for each country. Interrater consensus was reached on each category label. Hope-inspiring strategies included use of interpersonal self (listening, presence, empathy, directing the interaction away from hopelessness themes); involvement and caring for the family; sharing success stories; use of progress reports; empowerment; and referral to experts (psychologists, clinical nurse specialists). Differences were evident among the countries. Providing physical comfort was emphasized by Belgium, Colombia, and Canada but not mentioned by other countries. Nurses from France used strategies labeled \"positive provocation\" to keep patients self-sufficient, autonomous, and able to move beyond dwelling on hopelessness."} {"id": "PMID:1282847", "title": "Free L-phosphotyrosine activates human platelets: molecular evidence for a new signal transducer.", "content": "Human platelets, either purified or plasma-enriched, are activated when exposed to free L-phosphotyrosine. Physical aggregation is similar to that induced by collagen, although with distinctive biochemical features. Among these, a mobility shift of a GTP-binding protein specifically recognized by an anti-Ki-v-ras monoclonal antibody and an altered pattern of low molecular weight phosphorylated polypeptides are the most outstanding features. Since free phosphotyrosine is detected in platelets extracts, its role as a new signal transducer as well as its putative modulating action over protein phosphorylation are discussed.", "contents": "Free L-phosphotyrosine activates human platelets: molecular evidence for a new signal transducer. Human platelets, either purified or plasma-enriched, are activated when exposed to free L-phosphotyrosine. Physical aggregation is similar to that induced by collagen, although with distinctive biochemical features. Among these, a mobility shift of a GTP-binding protein specifically recognized by an anti-Ki-v-ras monoclonal antibody and an altered pattern of low molecular weight phosphorylated polypeptides are the most outstanding features. Since free phosphotyrosine is detected in platelets extracts, its role as a new signal transducer as well as its putative modulating action over protein phosphorylation are discussed."} {"id": "PMID:1282848", "title": "Purification and biochemical characterization of squirrel monkey retrovirus-H produced in a human lymphoblastoid cell line.", "content": "We found a type D retrovirus in a human lymphoblastoid cell line of B-cell lineage. Molecular cloning and nucleotide sequencing of the provirus genome revealed that this virus was closely related to squirrel monkey retrovirus (SMRV), and we designated this virus as SMRV-H. To investigate the relationship between these retroviruses, SMRV-H was purified from the virus-producing cells, and its biochemical properties were characterized. The cell-adhesive virus particles were successfully separated from the cell by a brief trypsin treatment and purified by velocity sedimentation. The purification of the virus was confirmed by electron microscopy. Major gag protein of the virus is phosphorylated, and has a molecular weight of 34 kDa. The virion-associated reverse transcriptase prefers Mg2+ to Mn2+. These properties of SMRV-H were almost the same as those of SMRV.", "contents": "Purification and biochemical characterization of squirrel monkey retrovirus-H produced in a human lymphoblastoid cell line. We found a type D retrovirus in a human lymphoblastoid cell line of B-cell lineage. Molecular cloning and nucleotide sequencing of the provirus genome revealed that this virus was closely related to squirrel monkey retrovirus (SMRV), and we designated this virus as SMRV-H. To investigate the relationship between these retroviruses, SMRV-H was purified from the virus-producing cells, and its biochemical properties were characterized. The cell-adhesive virus particles were successfully separated from the cell by a brief trypsin treatment and purified by velocity sedimentation. The purification of the virus was confirmed by electron microscopy. Major gag protein of the virus is phosphorylated, and has a molecular weight of 34 kDa. The virion-associated reverse transcriptase prefers Mg2+ to Mn2+. These properties of SMRV-H were almost the same as those of SMRV."} {"id": "PMID:1282849", "title": "Study on RNA synthesis in the retina and retinal pigment epithelium of mice by light microscopic radioautography.", "content": "With the aim of determining the distribution of the incorporation of 3H-uridine in both retina and retinal pigment epithelium (RPE), the mouse eyes at embryonic day 9.5 (E 9.5), E 12.5, E 14.5, E 16.5, E 18.5 of gestational ages, and postnatal day 1 (P 1), P 3, P 7, P 14 were analyzed by light microscopic radioautography. Small pieces of the ocular tissues were labelled with 3H-uridine in vitro and light microscopic radioautographs were prepared. The average grain numbers per cell of the respective regions of tissues were calculated. In the retina, the grain numbers increased gradually from E 9.5 to P 1 and reached the maximal value at P 1, and then decreased until P 14. However, the grain numbers were more in the vitreal portion than those in the scleral portion at E 16.5 and then became more in the scleral portion from E 18.5 to P 14. It is considered that the ganglion and bipolar cells finish the RNA synthesis earlier, while the photoreceptor cells do it later during the fetal and postnatal development. In the RPE, the grain numbers gradually increased from E 12.5 to P 7 and then decreased until P 14. Considering the same ages, the grain numbers increased in the following order, anterior, equatorial and posterior regions during embryonic stages, but decreased in the same order after birth. Therefore, it is suggested that the activity of RNA synthesis in PE cells is higher in the posterior region than in the anterior region during embryonic stages. But the activity ascends generally and becomes relatively higher in the anterior region, after birth. Comparing the retina and RPE, it was noted that the grain numbers in the RPE were more important than in the retina and that the maximal value was at P 1 in the retina, while it was at P 7 in the RPE. From these results, it can be concluded that the RNA synthesis ceases earlier in the retina than in the RPE.", "contents": "Study on RNA synthesis in the retina and retinal pigment epithelium of mice by light microscopic radioautography. With the aim of determining the distribution of the incorporation of 3H-uridine in both retina and retinal pigment epithelium (RPE), the mouse eyes at embryonic day 9.5 (E 9.5), E 12.5, E 14.5, E 16.5, E 18.5 of gestational ages, and postnatal day 1 (P 1), P 3, P 7, P 14 were analyzed by light microscopic radioautography. Small pieces of the ocular tissues were labelled with 3H-uridine in vitro and light microscopic radioautographs were prepared. The average grain numbers per cell of the respective regions of tissues were calculated. In the retina, the grain numbers increased gradually from E 9.5 to P 1 and reached the maximal value at P 1, and then decreased until P 14. However, the grain numbers were more in the vitreal portion than those in the scleral portion at E 16.5 and then became more in the scleral portion from E 18.5 to P 14. It is considered that the ganglion and bipolar cells finish the RNA synthesis earlier, while the photoreceptor cells do it later during the fetal and postnatal development. In the RPE, the grain numbers gradually increased from E 12.5 to P 7 and then decreased until P 14. Considering the same ages, the grain numbers increased in the following order, anterior, equatorial and posterior regions during embryonic stages, but decreased in the same order after birth. Therefore, it is suggested that the activity of RNA synthesis in PE cells is higher in the posterior region than in the anterior region during embryonic stages. But the activity ascends generally and becomes relatively higher in the anterior region, after birth. Comparing the retina and RPE, it was noted that the grain numbers in the RPE were more important than in the retina and that the maximal value was at P 1 in the retina, while it was at P 7 in the RPE. From these results, it can be concluded that the RNA synthesis ceases earlier in the retina than in the RPE."} {"id": "PMID:1282854", "title": "Effect of aseptic abscesses in protein-deficient rats on the relationship between interleukin-6 and the acute-phase protein, alpha 2-macroglobulin.", "content": "1. Rats established on a normal (20% protein) diet or a protein-deficient (3% protein) diet were given either a subcutaneous injection of turpentine (5 ml/kg), which induces formation of aseptic abscesses, or saline. Plasma samples were obtained at timed intervals (0-14 days) after the injection for determination of albumin, total protein, alpha 2-macroglobulin (a major acute-phase protein in the rat) and interleukin-6 concentrations. The magnitude and pattern of the acute-phase protein response was then compared with the local inflammatory reaction, assessed histologically, and with changes in the circulating concentration of interleukin-6, which is an important mediator of the acute-phase protein response. 2. After turpentine injection there was an early fall in the plasma albumin and total protein concentrations in both normal and protein-deficient rats. After 12 h the total protein concentration increased in both groups of animals reaching a peak at about 48 h, whereas the plasma albumin concentration continued to fall reaching a minimum at 48 h. The main alpha 2-macroglobulin response was delayed and attenuated in the protein-deficient rats (onset 9 versus 24 h, peak concentration 8.95 +/- 0.5 versus 5.33 +/- 0.75 g/l, P < 0.01, and area under the concentration-time curve 18.43 +/- 2.13 versus 7.96 +/- 1.48 g/l-1 days, P < 0.01, in the normal group and protein-deficient group, respectively). 3. The circulating interleukin-6 concentration showed a transient early rise at 1 h, and was followed by a larger more sustained peak at 6-48 h.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effect of aseptic abscesses in protein-deficient rats on the relationship between interleukin-6 and the acute-phase protein, alpha 2-macroglobulin. 1. Rats established on a normal (20% protein) diet or a protein-deficient (3% protein) diet were given either a subcutaneous injection of turpentine (5 ml/kg), which induces formation of aseptic abscesses, or saline. Plasma samples were obtained at timed intervals (0-14 days) after the injection for determination of albumin, total protein, alpha 2-macroglobulin (a major acute-phase protein in the rat) and interleukin-6 concentrations. The magnitude and pattern of the acute-phase protein response was then compared with the local inflammatory reaction, assessed histologically, and with changes in the circulating concentration of interleukin-6, which is an important mediator of the acute-phase protein response. 2. After turpentine injection there was an early fall in the plasma albumin and total protein concentrations in both normal and protein-deficient rats. After 12 h the total protein concentration increased in both groups of animals reaching a peak at about 48 h, whereas the plasma albumin concentration continued to fall reaching a minimum at 48 h. The main alpha 2-macroglobulin response was delayed and attenuated in the protein-deficient rats (onset 9 versus 24 h, peak concentration 8.95 +/- 0.5 versus 5.33 +/- 0.75 g/l, P < 0.01, and area under the concentration-time curve 18.43 +/- 2.13 versus 7.96 +/- 1.48 g/l-1 days, P < 0.01, in the normal group and protein-deficient group, respectively). 3. The circulating interleukin-6 concentration showed a transient early rise at 1 h, and was followed by a larger more sustained peak at 6-48 h.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282855", "title": "Measurement of surgical diathermy current during trans-urethral resection of the prostate gland.", "content": "A system is described that has been developed to measure the surgical diathermy current passing through the patient during each cut of a trans-urethral resection of the prostate gland (TURP), with 1.5% glycine solution as irrigant. The immediate aim was to distinguish capsular tissue of the male prostate gland from the hyperplastic adenomatous tissue within it. The ultimate aim was to prevent resection into the surgical capsule which can easily result in excessive blood loss and absorption of irrigant. The system was used in a conventional theatre setting with a commercial diathermy system (Eschmann TD 411-S) of known output characteristics. Measurements were made in 12 patients during resection with a standard loop, involving typically 75 cuts in each patient (60 in adenoma and 15 in capsule). In 8 of these patients this was followed by roller ball placement on typically 10 sites each of capsule or residual adenoma at very low diathermy settings. The results showed great variability both between patients, and between different cuts in the same patient, with no consistent difference between tissues identified under direct vision as adenoma and surgical capsule. Physical reasons are suggested for the observed variability, and it is concluded that it is not possible to use this technique to guide tissue resection in the prostate.", "contents": "Measurement of surgical diathermy current during trans-urethral resection of the prostate gland. A system is described that has been developed to measure the surgical diathermy current passing through the patient during each cut of a trans-urethral resection of the prostate gland (TURP), with 1.5% glycine solution as irrigant. The immediate aim was to distinguish capsular tissue of the male prostate gland from the hyperplastic adenomatous tissue within it. The ultimate aim was to prevent resection into the surgical capsule which can easily result in excessive blood loss and absorption of irrigant. The system was used in a conventional theatre setting with a commercial diathermy system (Eschmann TD 411-S) of known output characteristics. Measurements were made in 12 patients during resection with a standard loop, involving typically 75 cuts in each patient (60 in adenoma and 15 in capsule). In 8 of these patients this was followed by roller ball placement on typically 10 sites each of capsule or residual adenoma at very low diathermy settings. The results showed great variability both between patients, and between different cuts in the same patient, with no consistent difference between tissues identified under direct vision as adenoma and surgical capsule. Physical reasons are suggested for the observed variability, and it is concluded that it is not possible to use this technique to guide tissue resection in the prostate."} {"id": "PMID:1282853", "title": "Effect of the substitution of critical residues on the allorecognition of HLA-B27.", "content": "The three-dimensional structure of the HLA class I molecules has highlighted the importance of the \"groove\" formed by the helices. We used site-directed mutagenesis to construct a series of HLA-B27 mutants with different substitutions at the sites of the conserved amino acid residues of HLA-B27 subtypes, specifically residue 77 which is thought to be critical to the binding site of the molecule, and a residue at the CD8 binding site. We formed an anti-B27 CTL line and derived six anti-B27 clones. Each of the six clones showed a different pattern of reaction, reflecting the diversity of the epitopes recognized. All nine mutants were effective in altering allorecognition by HLA-B27 specific CTL, although positions 45 and 77 caused the most drastic effect. The residue in position 77 is also the last amino acid of the peptide sequence shared with Klebsiella. Our results highlight the importance of certain epitopes in allorecognition that may have important implications for the immunotherapy of autoimmune diseases.", "contents": "Effect of the substitution of critical residues on the allorecognition of HLA-B27. The three-dimensional structure of the HLA class I molecules has highlighted the importance of the \"groove\" formed by the helices. We used site-directed mutagenesis to construct a series of HLA-B27 mutants with different substitutions at the sites of the conserved amino acid residues of HLA-B27 subtypes, specifically residue 77 which is thought to be critical to the binding site of the molecule, and a residue at the CD8 binding site. We formed an anti-B27 CTL line and derived six anti-B27 clones. Each of the six clones showed a different pattern of reaction, reflecting the diversity of the epitopes recognized. All nine mutants were effective in altering allorecognition by HLA-B27 specific CTL, although positions 45 and 77 caused the most drastic effect. The residue in position 77 is also the last amino acid of the peptide sequence shared with Klebsiella. Our results highlight the importance of certain epitopes in allorecognition that may have important implications for the immunotherapy of autoimmune diseases."} {"id": "PMID:1282856", "title": "Expression of growth factor mRNA in rabbit PVR model systems.", "content": "Proliferative vitreoretinopathy (PVR) involves the formation of intravitreal fibrocellular membranes which may lead to traction retinal detachment and blindness. The cellular component of epiretinal membranes originates from the proliferation and migration of cells within the eye. Several growth factors and other cytokines are plausible candidates for directing the processes leading to membrane formation. A reproducible animal model is needed for experimental studies of cytokine expression during PVR induction or treatment. We found that intravitreal injection of > 10(6) mixed mononuclear leukocytes or adherent monocytes along with a trans-scleral incision through the pars plana leads to the development of PVR-like disease in rabbit eyes. The severity of the disease was related to the number of monocytes injected. Typically, organized membranes extending from the incision toward the optic nerve formed within one week. Progression to extensive traction retinal detachment required 1 to 4 weeks. Injection of up to 5 x 10(6) lymphocytes or freeze-thaw killed monocytes was ineffective, and coinjecting 100 micrograms endotoxin with the monocytes did not result in enhanced disease. The histological appearance of the epiretinal membranes was similar to human PVR membranes. Macrophage, cytokeratin-positive (epithelial), and fibroblast-like cells were present. Northern blot analysis of RNA extracted from the rabbit membranes revealed the presence of mRNA for acidic fibroblast growth factor (aFGF). Acidic FGF mRNA was not expressed by the injected monocytes. A comparable level of aFGF mRNA and also mRNAs for basic FGF, platelet-derived growth factor-B, and transforming growth factor beta were found in epiretinal membranes induced by a scleral incision in association with cryopexy.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Expression of growth factor mRNA in rabbit PVR model systems. Proliferative vitreoretinopathy (PVR) involves the formation of intravitreal fibrocellular membranes which may lead to traction retinal detachment and blindness. The cellular component of epiretinal membranes originates from the proliferation and migration of cells within the eye. Several growth factors and other cytokines are plausible candidates for directing the processes leading to membrane formation. A reproducible animal model is needed for experimental studies of cytokine expression during PVR induction or treatment. We found that intravitreal injection of > 10(6) mixed mononuclear leukocytes or adherent monocytes along with a trans-scleral incision through the pars plana leads to the development of PVR-like disease in rabbit eyes. The severity of the disease was related to the number of monocytes injected. Typically, organized membranes extending from the incision toward the optic nerve formed within one week. Progression to extensive traction retinal detachment required 1 to 4 weeks. Injection of up to 5 x 10(6) lymphocytes or freeze-thaw killed monocytes was ineffective, and coinjecting 100 micrograms endotoxin with the monocytes did not result in enhanced disease. The histological appearance of the epiretinal membranes was similar to human PVR membranes. Macrophage, cytokeratin-positive (epithelial), and fibroblast-like cells were present. Northern blot analysis of RNA extracted from the rabbit membranes revealed the presence of mRNA for acidic fibroblast growth factor (aFGF). Acidic FGF mRNA was not expressed by the injected monocytes. A comparable level of aFGF mRNA and also mRNAs for basic FGF, platelet-derived growth factor-B, and transforming growth factor beta were found in epiretinal membranes induced by a scleral incision in association with cryopexy.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282857", "title": "c-Src and mitosis.", "content": "The transforming potential and by inference the physiological function of the proto-oncoprotein pp60c-src closely correlate with the level of its protein tyrosine kinase activity. We have investigated the cell cycle-dependent regulation of this activity using mouse fibroblasts overexpressing chicken or mouse pp60c-src as a model system. During mitosis pp60c-src becomes phosphorylated at specific serine and threonine residues by p34cdc2. At the same time its tyrosine kinase activity, assayed in vitro, is increased approximately twofold and accessibility of its SH2 domain for binding relevant phosphotyrosine-containing ligands increases by about 15-fold. A kinase-defective mutant of pp60c-src exhibits a substantial (50-70%) decrease in phosphorylation at Tyr527 during mitosis. Phosphorylation of this residue negatively regulates kinase activity. Indirect evidence indicates a lesser decrease in wild-type pp60c-src Tyr527 phosphorylation during mitosis. Coordinate mutation of the mitosis-specific phosphorylation (MSP) sites in kinase-defective pp60c-src greatly reduces, though does not abolish, its mitosis-specific tyrosine dephosphorylation. Similarly, coordinate mutation of the three MSP sites in chicken pp60c-src or the corresponding two sites in mouse pp60c-src does not completely block mitotic stimulation of kinase activity. Thus, additional events beyond p34cdc2-mediated phosphorylation are involved in cell-cycle dependent regulation of pp60c-src activity. This is also suggested by the stimulation of pp60c-src kinase activity and decrease in phosphorylation of Tyr527 observed following treatment of fibroblasts with okadaic acid, a potent inhibitor of types 1 and 2A serine/threonine phosphatases. The potential role of cell cycle-dependent regulation of phosphatases and kinases acting on the regulatory tyrosine residue of pp60c-src is discussed.", "contents": "c-Src and mitosis. The transforming potential and by inference the physiological function of the proto-oncoprotein pp60c-src closely correlate with the level of its protein tyrosine kinase activity. We have investigated the cell cycle-dependent regulation of this activity using mouse fibroblasts overexpressing chicken or mouse pp60c-src as a model system. During mitosis pp60c-src becomes phosphorylated at specific serine and threonine residues by p34cdc2. At the same time its tyrosine kinase activity, assayed in vitro, is increased approximately twofold and accessibility of its SH2 domain for binding relevant phosphotyrosine-containing ligands increases by about 15-fold. A kinase-defective mutant of pp60c-src exhibits a substantial (50-70%) decrease in phosphorylation at Tyr527 during mitosis. Phosphorylation of this residue negatively regulates kinase activity. Indirect evidence indicates a lesser decrease in wild-type pp60c-src Tyr527 phosphorylation during mitosis. Coordinate mutation of the mitosis-specific phosphorylation (MSP) sites in kinase-defective pp60c-src greatly reduces, though does not abolish, its mitosis-specific tyrosine dephosphorylation. Similarly, coordinate mutation of the three MSP sites in chicken pp60c-src or the corresponding two sites in mouse pp60c-src does not completely block mitotic stimulation of kinase activity. Thus, additional events beyond p34cdc2-mediated phosphorylation are involved in cell-cycle dependent regulation of pp60c-src activity. This is also suggested by the stimulation of pp60c-src kinase activity and decrease in phosphorylation of Tyr527 observed following treatment of fibroblasts with okadaic acid, a potent inhibitor of types 1 and 2A serine/threonine phosphatases. The potential role of cell cycle-dependent regulation of phosphatases and kinases acting on the regulatory tyrosine residue of pp60c-src is discussed."} {"id": "PMID:1282858", "title": "Prostacyclin synthesis and stimulation of cyclic AMP production in ovine fetal vasculature: heterogeneity in pulmonary and systemic arteries.", "content": "Prostacyclin (PGI2) is an important local mediator of vasomotor tone in the fetus and newborn, acting via stimulation of cAMP production by vascular smooth muscle (VSM) adenylate cyclase. In this investigation PGI2 and prostaglandin (PG) E2 synthesis and stimulation of cAMP production were compared in vitro in ovine fetal pulmonary versus systemic (mesenteric) arteries. PGI2 synthesis was similar in the pulmonary and systemic arteries (2.4 +/- 0.2 and 2.6 +/- 0.3 ng/mg protein.h, respectively), as was PGE2 synthesis (1.9 +/- 0.2 and 1.5 +/- 0.2 ng/mg protein.h, respectively); synthesis was greater for PGI2 versus PGE2 in both artery types. 65-71% of PGI2 synthesis and 51-59% of PGE2 synthesis occurred in the endothelium. Basal (nonstimulated) cAMP production was fully attenuated by indomethacin, indicating that it is mediated exclusively by endogenous PG. Basal cAMP production was 3.8-fold less in pulmonary versus systemic arteries, and this was related to a 9.7-fold difference in responsiveness to PG. A 14.7-fold difference in the response to forskolin indicates that underlying mechanism may be a disparity in the quantity and/or function of the adenylate cyclase enzyme complex. Thus, prostacyclin and PGE2 synthesis are comparable in ovine fetal pulmonary versus systemic arteries, but the cAMP response to the prostanoids is markedly greater in the latter artery type due to differences in the activation of adenylate cyclase. This heterogeneity in VSM intracellular signalling may contribute to differential vasomotor tone and responses in the fetal pulmonary and systemic circulation.", "contents": "Prostacyclin synthesis and stimulation of cyclic AMP production in ovine fetal vasculature: heterogeneity in pulmonary and systemic arteries. Prostacyclin (PGI2) is an important local mediator of vasomotor tone in the fetus and newborn, acting via stimulation of cAMP production by vascular smooth muscle (VSM) adenylate cyclase. In this investigation PGI2 and prostaglandin (PG) E2 synthesis and stimulation of cAMP production were compared in vitro in ovine fetal pulmonary versus systemic (mesenteric) arteries. PGI2 synthesis was similar in the pulmonary and systemic arteries (2.4 +/- 0.2 and 2.6 +/- 0.3 ng/mg protein.h, respectively), as was PGE2 synthesis (1.9 +/- 0.2 and 1.5 +/- 0.2 ng/mg protein.h, respectively); synthesis was greater for PGI2 versus PGE2 in both artery types. 65-71% of PGI2 synthesis and 51-59% of PGE2 synthesis occurred in the endothelium. Basal (nonstimulated) cAMP production was fully attenuated by indomethacin, indicating that it is mediated exclusively by endogenous PG. Basal cAMP production was 3.8-fold less in pulmonary versus systemic arteries, and this was related to a 9.7-fold difference in responsiveness to PG. A 14.7-fold difference in the response to forskolin indicates that underlying mechanism may be a disparity in the quantity and/or function of the adenylate cyclase enzyme complex. Thus, prostacyclin and PGE2 synthesis are comparable in ovine fetal pulmonary versus systemic arteries, but the cAMP response to the prostanoids is markedly greater in the latter artery type due to differences in the activation of adenylate cyclase. This heterogeneity in VSM intracellular signalling may contribute to differential vasomotor tone and responses in the fetal pulmonary and systemic circulation."} {"id": "PMID:1282859", "title": "Expression of tenascin mRNA in mesoderm during Xenopus laevis embryogenesis: the potential role of mesoderm patterning in tenascin regionalization.", "content": "In Xenopus embryos, the extracellular matrix (ECM) protein tenascin (TN) is expressed dorsally in a very restricted pattern. We have studied the spatial and temporal expression of TN mRNA in tailbud-stage embryos by RNAase protection and in situ hybridization using a cDNA probe for Xenopus TN obtained by PCR amplification. We report that TN transcripts are principally expressed in cells dispersed around the neural tube and notochord as well as in myotome and sclerotome cells. No TN mRNA could be detected in lateral plate mesoderm, but expression was detectable beneath tail fin epidermis. In a second series of experiments, we studied the expression of TN mRNA and protein in combinations between animal and vegetal stage-6 blastomeres and in stage-8 blastula animal caps treated with activin A or basic fibroblastic growth factor (b-FGF). Isolated animal cap tissue cultured alone differentiates into epidermis, which expresses neither TN protein nor TN mRNA. TN expression is, however, elicited in response to isolated dorsal vegetal blastomeres and in response to high concentrations of activin, both of which treatments lead to formation of muscle and/or notochord. Low concentrations of activin, and ventral vegetal blastomeres, treatments that induce mesoderm of ventral character, are poor inducers of TN. However, b-FGF, which also induces ventral mesoderm, elicits strong expression. These results indicate that TN regionalization is a complex process, dependent both on the pattern of differentiation of mesodermal tissues and on the agent with which they are induced. The data further show that \"ventral mesoderm\" induced by low concentrations of activin is distinct from that induced by b-FGF, and imply that activin induces ventral mesoderm of the trunk while b-FGF induces posterior mesoderm of the tailbud.", "contents": "Expression of tenascin mRNA in mesoderm during Xenopus laevis embryogenesis: the potential role of mesoderm patterning in tenascin regionalization. In Xenopus embryos, the extracellular matrix (ECM) protein tenascin (TN) is expressed dorsally in a very restricted pattern. We have studied the spatial and temporal expression of TN mRNA in tailbud-stage embryos by RNAase protection and in situ hybridization using a cDNA probe for Xenopus TN obtained by PCR amplification. We report that TN transcripts are principally expressed in cells dispersed around the neural tube and notochord as well as in myotome and sclerotome cells. No TN mRNA could be detected in lateral plate mesoderm, but expression was detectable beneath tail fin epidermis. In a second series of experiments, we studied the expression of TN mRNA and protein in combinations between animal and vegetal stage-6 blastomeres and in stage-8 blastula animal caps treated with activin A or basic fibroblastic growth factor (b-FGF). Isolated animal cap tissue cultured alone differentiates into epidermis, which expresses neither TN protein nor TN mRNA. TN expression is, however, elicited in response to isolated dorsal vegetal blastomeres and in response to high concentrations of activin, both of which treatments lead to formation of muscle and/or notochord. Low concentrations of activin, and ventral vegetal blastomeres, treatments that induce mesoderm of ventral character, are poor inducers of TN. However, b-FGF, which also induces ventral mesoderm, elicits strong expression. These results indicate that TN regionalization is a complex process, dependent both on the pattern of differentiation of mesodermal tissues and on the agent with which they are induced. The data further show that \"ventral mesoderm\" induced by low concentrations of activin is distinct from that induced by b-FGF, and imply that activin induces ventral mesoderm of the trunk while b-FGF induces posterior mesoderm of the tailbud."} {"id": "PMID:1282860", "title": "Drosophila PS2 integrin mediates RGD-dependent cell-matrix interactions.", "content": "Integrins are a family of transmembrane glycoproteins that mediate cell-matrix and cell-cell interactions. We have transfected cultured Drosophila cells with genes that express the Drosophila PS2 integrin. We demonstrate that this integrin is expressed on the surface of the cells and can mediate cell spreading on an undefined component of fetal calf serum or on the purified vertebrate matrix molecules vitronectin and fibronectin. Additionally, PS2 integrin can cause cell spreading on RGD peptide. The spreading on matrix components or RGD peptide can be inhibited by soluble RGD peptide and is dependent on divalent cations.", "contents": "Drosophila PS2 integrin mediates RGD-dependent cell-matrix interactions. Integrins are a family of transmembrane glycoproteins that mediate cell-matrix and cell-cell interactions. We have transfected cultured Drosophila cells with genes that express the Drosophila PS2 integrin. We demonstrate that this integrin is expressed on the surface of the cells and can mediate cell spreading on an undefined component of fetal calf serum or on the purified vertebrate matrix molecules vitronectin and fibronectin. Additionally, PS2 integrin can cause cell spreading on RGD peptide. The spreading on matrix components or RGD peptide can be inhibited by soluble RGD peptide and is dependent on divalent cations."} {"id": "PMID:1282861", "title": "Synapse-specific expression of acetylcholine receptor genes and their products at original synaptic sites in rat soleus muscle fibres regenerating in the absence of innervation.", "content": "To test the hypothesis that synaptic basal lamina can induce synapse-specific expression of acetylcholine receptor (AChR) genes, we examined the levels mRNA for the alpha- and epsilon-subunits of the AChR in regenerating rat soleus muscles up to 17 days of regeneration. Following destruction of all muscle fibres and their nuclei by exposure to venom of the Australian tiger snake, new fibres regenerated within the original basal lamina sheaths. Northern blots showed that original mRNA was lost during degeneration. Early in regeneration, both alpha- and epsilon-subunit mRNAs were present throughout the muscle fibres but in situ hybridization showed them to be concentrated primarily at original synaptic sites, even when the nerve was absent during regeneration. A similar concentration was seen in denervated regenerating muscles kept active by electrical stimulation and in muscles frozen 41-44 hours after venom injection to destroy all cells in the synaptic region of the muscle. Acetylcholine-gated ion channels with properties similar to those at normal neuromuscular junctions were concentrated at original synaptic sites on denervated stimulated muscles. Taken together, these findings provide strong evidence that factors that induce the synapse-specific expression of AChR genes are stably bound to synaptic basal lamina.", "contents": "Synapse-specific expression of acetylcholine receptor genes and their products at original synaptic sites in rat soleus muscle fibres regenerating in the absence of innervation. To test the hypothesis that synaptic basal lamina can induce synapse-specific expression of acetylcholine receptor (AChR) genes, we examined the levels mRNA for the alpha- and epsilon-subunits of the AChR in regenerating rat soleus muscles up to 17 days of regeneration. Following destruction of all muscle fibres and their nuclei by exposure to venom of the Australian tiger snake, new fibres regenerated within the original basal lamina sheaths. Northern blots showed that original mRNA was lost during degeneration. Early in regeneration, both alpha- and epsilon-subunit mRNAs were present throughout the muscle fibres but in situ hybridization showed them to be concentrated primarily at original synaptic sites, even when the nerve was absent during regeneration. A similar concentration was seen in denervated regenerating muscles kept active by electrical stimulation and in muscles frozen 41-44 hours after venom injection to destroy all cells in the synaptic region of the muscle. Acetylcholine-gated ion channels with properties similar to those at normal neuromuscular junctions were concentrated at original synaptic sites on denervated stimulated muscles. Taken together, these findings provide strong evidence that factors that induce the synapse-specific expression of AChR genes are stably bound to synaptic basal lamina."} {"id": "PMID:1282862", "title": "Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders.", "content": "Hydroxyethylrutosides is a standardised mixture of semisynthetic flavonoids, mainly mono-, di-, tri-, and tetrahydroxyethylrutosides, which acts primarily on the microvascular endothelium to reduce hyperpermeability and oedema. In patients with chronic venous insufficiency or diabetes, hydroxyethylrutosides improves microvascular perfusion and microcirculation, and reduces erythrocyte aggregation. The preparation also has a possible protective effect on the vascular endothelium. In short to medium term placebo-controlled studies (up to 6 months) hydroxyethylrutosides therapy improved signs and symptoms of chronic venous insufficiency, including venous insufficiency associated with pregnancy and lymphoedema, and was well tolerated. However, the long term effects of hydroxyethylrutosides administration have yet to be demonstrated. The preparation also alleviated symptoms in patients with severe haemorrhoids, although there were no corresponding objective improvements. Hydroxyethylrutosides administration has been associated with reductions in retinal vascular permeability in patients with diabetic retinopathy but has no apparent effect on signs of retinal haemorrhage, although a reduction in oedema and haemorrhage has been reported in other patients receiving oral hydroxyethylrutosides in the acute phase of central retinal vein occlusion. There are only limited effective pharmacological treatment options for patients with chronic venous insufficiency or lymphoedema, and hydroxyethylrutosides clearly improves signs and symptoms of these disorders. While its role in diabetic retinopathy and haemorrhoids requires some clarification, hydroxyethylrutosides therapy shows promise as a useful additional option for the management of oedema and other symptoms of chronic venous insufficiency.", "contents": "Hydroxyethylrutosides. A review of its pharmacology, and therapeutic efficacy in venous insufficiency and related disorders. Hydroxyethylrutosides is a standardised mixture of semisynthetic flavonoids, mainly mono-, di-, tri-, and tetrahydroxyethylrutosides, which acts primarily on the microvascular endothelium to reduce hyperpermeability and oedema. In patients with chronic venous insufficiency or diabetes, hydroxyethylrutosides improves microvascular perfusion and microcirculation, and reduces erythrocyte aggregation. The preparation also has a possible protective effect on the vascular endothelium. In short to medium term placebo-controlled studies (up to 6 months) hydroxyethylrutosides therapy improved signs and symptoms of chronic venous insufficiency, including venous insufficiency associated with pregnancy and lymphoedema, and was well tolerated. However, the long term effects of hydroxyethylrutosides administration have yet to be demonstrated. The preparation also alleviated symptoms in patients with severe haemorrhoids, although there were no corresponding objective improvements. Hydroxyethylrutosides administration has been associated with reductions in retinal vascular permeability in patients with diabetic retinopathy but has no apparent effect on signs of retinal haemorrhage, although a reduction in oedema and haemorrhage has been reported in other patients receiving oral hydroxyethylrutosides in the acute phase of central retinal vein occlusion. There are only limited effective pharmacological treatment options for patients with chronic venous insufficiency or lymphoedema, and hydroxyethylrutosides clearly improves signs and symptoms of these disorders. While its role in diabetic retinopathy and haemorrhoids requires some clarification, hydroxyethylrutosides therapy shows promise as a useful additional option for the management of oedema and other symptoms of chronic venous insufficiency."} {"id": "PMID:1282864", "title": "Current status of phosphodiesterase inhibitors in the treatment of congestive heart failure.", "content": "The phosphodiesterase inhibitors have been recognised as potent inotropic and vasodilating drugs. In acute congestive heart failure they increase cardiac output, decrease left pulmonary capillary wedge pressure, and reduce total peripheral resistance with an improvement in loading conditions of the failing heart. Their potency in reversal of symptoms of acute congestive heart failure is quite similar to, or even better than, treatment with intravenous catecholamines and sodium nitroprusside. In chronic congestive heart failure, however, these agents increase mortality and have deleterious effects in the outcome of patients with severe left ventricular dysfunction.", "contents": "Current status of phosphodiesterase inhibitors in the treatment of congestive heart failure. The phosphodiesterase inhibitors have been recognised as potent inotropic and vasodilating drugs. In acute congestive heart failure they increase cardiac output, decrease left pulmonary capillary wedge pressure, and reduce total peripheral resistance with an improvement in loading conditions of the failing heart. Their potency in reversal of symptoms of acute congestive heart failure is quite similar to, or even better than, treatment with intravenous catecholamines and sodium nitroprusside. In chronic congestive heart failure, however, these agents increase mortality and have deleterious effects in the outcome of patients with severe left ventricular dysfunction."} {"id": "PMID:1282865", "title": "Interferons in multiple sclerosis. A review of the evidence.", "content": "Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterised clinically by relapses and remissions, and leading eventually to chronic disability. Despite an enormous amount of research, the cause of MS remains unknown; however, pathological, genetic, and immunological features have been identified that suggest the disease has an autoimmune basis. Accordingly, current therapy of MS includes corticotrophin or corticosteroids for acute exacerbations, and more potent immunosuppressive drugs for severe cases unresponsive to steroids. All of these agents can cause serious adverse reactions. There is an urgent need for immunotherapy that is less toxic, that can be given early and perhaps indefinitely, and that will prevent relapses and progression of the disease. Our current knowledge of the effects of interferons (IFNs) in MS is based on the results of laboratory research and clinical therapeutic trials carried out over the past decade. Existing evidence points to the conclusion that the effects of the IFNs in MS are mediated by immunoregulatory rather than antiviral or nonspecific mechanisms. Administration of IFN gamma increases the exacerbation rate, and IFN gamma as well as other cytokines may be involved in the pathogenesis of MS lesions. In contrast, studies of IFN beta show that it tends to inhibit the activity of IFN gamma and appears to prevent disease activity. Intrathecal administration of IFN beta, although effective, is cumbersome and potentially hazardous. A large multicentre placebo-controlled trial of systemic recombinant IFN beta was recently conducted in the US, and the results of the first 2 years of treatment were considered sufficiently encouraging that an application for licensing was submitted to the Food and Drug Administration in June 1992. If approved, it will be the first new agent licensed for clinical use in MS in over 20 years. The study will continue under double-blind conditions for at least another year, and a second trial of systemic recombinant IFN beta therapy is also in progress. These studies should provide definitive answers to questions about the role of IFNs in the pathogenesis of MS, as well as the place of recombinant IFN beta as an effective therapeutic agent.", "contents": "Interferons in multiple sclerosis. A review of the evidence. Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterised clinically by relapses and remissions, and leading eventually to chronic disability. Despite an enormous amount of research, the cause of MS remains unknown; however, pathological, genetic, and immunological features have been identified that suggest the disease has an autoimmune basis. Accordingly, current therapy of MS includes corticotrophin or corticosteroids for acute exacerbations, and more potent immunosuppressive drugs for severe cases unresponsive to steroids. All of these agents can cause serious adverse reactions. There is an urgent need for immunotherapy that is less toxic, that can be given early and perhaps indefinitely, and that will prevent relapses and progression of the disease. Our current knowledge of the effects of interferons (IFNs) in MS is based on the results of laboratory research and clinical therapeutic trials carried out over the past decade. Existing evidence points to the conclusion that the effects of the IFNs in MS are mediated by immunoregulatory rather than antiviral or nonspecific mechanisms. Administration of IFN gamma increases the exacerbation rate, and IFN gamma as well as other cytokines may be involved in the pathogenesis of MS lesions. In contrast, studies of IFN beta show that it tends to inhibit the activity of IFN gamma and appears to prevent disease activity. Intrathecal administration of IFN beta, although effective, is cumbersome and potentially hazardous. A large multicentre placebo-controlled trial of systemic recombinant IFN beta was recently conducted in the US, and the results of the first 2 years of treatment were considered sufficiently encouraging that an application for licensing was submitted to the Food and Drug Administration in June 1992. If approved, it will be the first new agent licensed for clinical use in MS in over 20 years. The study will continue under double-blind conditions for at least another year, and a second trial of systemic recombinant IFN beta therapy is also in progress. These studies should provide definitive answers to questions about the role of IFNs in the pathogenesis of MS, as well as the place of recombinant IFN beta as an effective therapeutic agent."} {"id": "PMID:1282866", "title": "Disseminated intravascular coagulation. Approach to treatment.", "content": "Disseminated intravascular coagulation (DIC) is a syndrome caused by the systemic generation of thrombin. Most cases are due to pathological activation of the intrinsic coagulation systems (e.g. in sepsis), and/or the extrinsic system (e.g. in malignancy and head trauma). Diagnosis is made by finding abnormalities in at least 3 of 4 laboratory values, namely prothrombin time, platelet count, fibrinogen and fibrinogen/fibrin degradation products. The most common clinical manifestation of DIC is bleeding, with thrombosis in less than 10% of acute cases but more frequently encountered in chronic DIC associated with malignancy. Acute DIC must first be treated by specific therapy of the underlying disease and general support measures. If serial clinical and laboratory monitoring improves, no further treatment is required. If severe or life-threatening haemorrhage occurs or a thrombotic event ensues, heparin anticoagulation followed by aggressive replacement with platelets, fresh plasma and possibly cryoprecipitate is indicated. Heparin doses should be 'therapeutic' (i.e. adequate to overcome the coagulant forces that may have produced a relative heparin-resistant state in the blood). Chronic DIC with haemorrhage, or more usually thrombosis, should also be treated with heparin; warfarin is ineffective. If DIC persists because, for example, a tumour does not regress, long term outpatient subcutaneous heparin therapy may be required.", "contents": "Disseminated intravascular coagulation. Approach to treatment. Disseminated intravascular coagulation (DIC) is a syndrome caused by the systemic generation of thrombin. Most cases are due to pathological activation of the intrinsic coagulation systems (e.g. in sepsis), and/or the extrinsic system (e.g. in malignancy and head trauma). Diagnosis is made by finding abnormalities in at least 3 of 4 laboratory values, namely prothrombin time, platelet count, fibrinogen and fibrinogen/fibrin degradation products. The most common clinical manifestation of DIC is bleeding, with thrombosis in less than 10% of acute cases but more frequently encountered in chronic DIC associated with malignancy. Acute DIC must first be treated by specific therapy of the underlying disease and general support measures. If serial clinical and laboratory monitoring improves, no further treatment is required. If severe or life-threatening haemorrhage occurs or a thrombotic event ensues, heparin anticoagulation followed by aggressive replacement with platelets, fresh plasma and possibly cryoprecipitate is indicated. Heparin doses should be 'therapeutic' (i.e. adequate to overcome the coagulant forces that may have produced a relative heparin-resistant state in the blood). Chronic DIC with haemorrhage, or more usually thrombosis, should also be treated with heparin; warfarin is ineffective. If DIC persists because, for example, a tumour does not regress, long term outpatient subcutaneous heparin therapy may be required."} {"id": "PMID:1282867", "title": "Treatment of bacteriuria in pregnancy.", "content": "The presence of bacteriuria during gestation increases the chance of acute pyelonephritis. Treatment of bacteriuria in pregnancy reduces subsequent development of symptomatic disease. Numerous studies have shown that single-dose therapy for asymptomatic bacteriuria is as effective as longer course of treatment. Single-dose therapy also has the advantages of improved compliance, reduced costs, and less adverse effects resulting from long term therapy. Follow-up cultures following antimicrobial treatment should be used for early detection of recurrence or relapse. If the urine culture yields no growth, a urine culture at a monthly interval will suffice. If on the other hand bacteriuria is present, a repeat course of antimicrobial therapy should be chosen based on antimicrobial susceptibility testing. A longer course of therapy, possibly with a different drug, is recommended for women with a positive follow-up urine culture. Acute cystitis may be treated with the same regimen as asymptomatic bacteriuria. When upper urinary tract infection is suspected, hospitalisation and a longer course of therapy is recommended. If the organism is susceptible to cefalexin or nitrofurantoin, postcoital prophylaxis with either agent for the remainder of the pregnancy may be beneficial.", "contents": "Treatment of bacteriuria in pregnancy. The presence of bacteriuria during gestation increases the chance of acute pyelonephritis. Treatment of bacteriuria in pregnancy reduces subsequent development of symptomatic disease. Numerous studies have shown that single-dose therapy for asymptomatic bacteriuria is as effective as longer course of treatment. Single-dose therapy also has the advantages of improved compliance, reduced costs, and less adverse effects resulting from long term therapy. Follow-up cultures following antimicrobial treatment should be used for early detection of recurrence or relapse. If the urine culture yields no growth, a urine culture at a monthly interval will suffice. If on the other hand bacteriuria is present, a repeat course of antimicrobial therapy should be chosen based on antimicrobial susceptibility testing. A longer course of therapy, possibly with a different drug, is recommended for women with a positive follow-up urine culture. Acute cystitis may be treated with the same regimen as asymptomatic bacteriuria. When upper urinary tract infection is suspected, hospitalisation and a longer course of therapy is recommended. If the organism is susceptible to cefalexin or nitrofurantoin, postcoital prophylaxis with either agent for the remainder of the pregnancy may be beneficial."} {"id": "PMID:1282868", "title": "A clinical guide to antipsychotic drugs.", "content": "Antipsychotic medications have altered the treatment of psychosis. The effect of typical agents is presumed to be associated with dopamine D2-receptor blockade. Response to these drugs can be evaluated by measuring target symptoms. Behavioural symptoms are generally first to respond, followed by affective symptoms, and then symptoms of disturbed cognition and perception. Predictors of response include age of onset, premorbid function, family history, cognitive function, ventricle size, and levels of homovanillic acid. As all conventional antipsychotic medications of comparable dose are generally of equivalent efficacy (with the exception of clozapine), choice is based on past response and the patient's tolerance of adverse effects. When antipsychotic agents are administered in the short term to control agitated dangerous behaviour, they can be given intramuscularly and augmented with benzodiazepines. For the ongoing treatment of psychosis, haloperidol 5 mg/day, or its equivalent, is usually sufficient. Continuation of treatment after an acute episode may be decided on the basis of chronicity of the psychotic illness. Relapse rates are higher when patients do not continue to receive medication. Lower maintenance doses may result in higher relapse rates but fewer adverse effects. Long-acting intramuscular depot preparations may be used to aid compliance in long term therapy. Adverse reactions correlate with potency. High potency drugs (i.e. those with greater D2 postsynaptic receptor affinity) are generally associated with extrapyramidal symptoms, including acute dystonic reactions, akathisia, tardive dyskinesia and Parkinsonism. Neuroleptic malignant syndrome is associated with all neuroleptic drugs. Low potency agents may cause orthostatic hypotension, sedation and anticholinergic effects. Clozapine has been shown to be effective in 30 to 40% of patients resistant to previous treatment. It does not cause extrapyramidal symptoms, but does have side effects similar to those of low potency agents and may cause agranulocytosis; it is therefore reserved for those patients who have not responded to therapy with 2 other agents. Several other atypical drugs are currently being investigated.", "contents": "A clinical guide to antipsychotic drugs. Antipsychotic medications have altered the treatment of psychosis. The effect of typical agents is presumed to be associated with dopamine D2-receptor blockade. Response to these drugs can be evaluated by measuring target symptoms. Behavioural symptoms are generally first to respond, followed by affective symptoms, and then symptoms of disturbed cognition and perception. Predictors of response include age of onset, premorbid function, family history, cognitive function, ventricle size, and levels of homovanillic acid. As all conventional antipsychotic medications of comparable dose are generally of equivalent efficacy (with the exception of clozapine), choice is based on past response and the patient's tolerance of adverse effects. When antipsychotic agents are administered in the short term to control agitated dangerous behaviour, they can be given intramuscularly and augmented with benzodiazepines. For the ongoing treatment of psychosis, haloperidol 5 mg/day, or its equivalent, is usually sufficient. Continuation of treatment after an acute episode may be decided on the basis of chronicity of the psychotic illness. Relapse rates are higher when patients do not continue to receive medication. Lower maintenance doses may result in higher relapse rates but fewer adverse effects. Long-acting intramuscular depot preparations may be used to aid compliance in long term therapy. Adverse reactions correlate with potency. High potency drugs (i.e. those with greater D2 postsynaptic receptor affinity) are generally associated with extrapyramidal symptoms, including acute dystonic reactions, akathisia, tardive dyskinesia and Parkinsonism. Neuroleptic malignant syndrome is associated with all neuroleptic drugs. Low potency agents may cause orthostatic hypotension, sedation and anticholinergic effects. Clozapine has been shown to be effective in 30 to 40% of patients resistant to previous treatment. It does not cause extrapyramidal symptoms, but does have side effects similar to those of low potency agents and may cause agranulocytosis; it is therefore reserved for those patients who have not responded to therapy with 2 other agents. Several other atypical drugs are currently being investigated."} {"id": "PMID:1282869", "title": "Moxonidine. A review of its pharmacology, and therapeutic use in essential hypertension.", "content": "Interest in centrally acting antihypertensive agents has recently been renewed with the development of drugs that are associated with fewer central adverse effects (e.g. sedation, dry mouth) than the older drugs in this class. Moxonidine reduces sympathetic outflow and hence lowers blood pressure through stimulation of central imidazoline receptors. Blood pressure is decreased by 10 to 20% during moxonidine treatment, with about 70% of patients with mild to moderate hypertension achieving a diastolic pressure of < 90mm Hg. The relatively few published comparative studies demonstrate that moxonidine has efficacy comparable with that of clonidine, prazosin, atenolol, nifedipine, captopril and hydrochlorothiazide. It is at least as well tolerated as these agents in trials and, importantly, appears to cause less sedation and dry mouth than clonidine. Compliance may be aided by the once- or twice-daily administration schedule with moxonidine, and dosage adjustment is only necessary in patients with moderate renal impairment. While its published clinical data base needs further expanding, moxonidine thus appears to be a more attractive option than oral clonidine, and may be considered along with the other classes of drug used to treat patients with mild to moderate hypertension.", "contents": "Moxonidine. A review of its pharmacology, and therapeutic use in essential hypertension. Interest in centrally acting antihypertensive agents has recently been renewed with the development of drugs that are associated with fewer central adverse effects (e.g. sedation, dry mouth) than the older drugs in this class. Moxonidine reduces sympathetic outflow and hence lowers blood pressure through stimulation of central imidazoline receptors. Blood pressure is decreased by 10 to 20% during moxonidine treatment, with about 70% of patients with mild to moderate hypertension achieving a diastolic pressure of < 90mm Hg. The relatively few published comparative studies demonstrate that moxonidine has efficacy comparable with that of clonidine, prazosin, atenolol, nifedipine, captopril and hydrochlorothiazide. It is at least as well tolerated as these agents in trials and, importantly, appears to cause less sedation and dry mouth than clonidine. Compliance may be aided by the once- or twice-daily administration schedule with moxonidine, and dosage adjustment is only necessary in patients with moderate renal impairment. While its published clinical data base needs further expanding, moxonidine thus appears to be a more attractive option than oral clonidine, and may be considered along with the other classes of drug used to treat patients with mild to moderate hypertension."} {"id": "PMID:1282870", "title": "Mechanism and prediction of nonspecific toxicity to fish using bioconcentration characteristics.", "content": "A basic theory of nonspecific toxicity has been developed using bioconcentration as a basis and applying kinetic relationships developed in previous work. This approach has involved calculation of the critical volume fraction and critical concentration in lipid tissue of fish for a variety of organic compounds at the lethal level. Corrections to previous data sets for time period of exposure and inclusion of biodegradable compounds did not make a significant improvement in the values obtained. A new data base with compounds containing a wide range of Kow values gave results for critical volume and concentration similar to previous work. The influence of experimental procedures and methods for data development are considered. The basic theoretical derivation developed was found to provide a basis for predicting the approximate nonspecific toxicity of nondegradable lipophilic organic compounds at different exposure time periods. This requires a knowledge of the Kow value and the clearance rate constant (k2) which can be calculated from the Kow value.", "contents": "Mechanism and prediction of nonspecific toxicity to fish using bioconcentration characteristics. A basic theory of nonspecific toxicity has been developed using bioconcentration as a basis and applying kinetic relationships developed in previous work. This approach has involved calculation of the critical volume fraction and critical concentration in lipid tissue of fish for a variety of organic compounds at the lethal level. Corrections to previous data sets for time period of exposure and inclusion of biodegradable compounds did not make a significant improvement in the values obtained. A new data base with compounds containing a wide range of Kow values gave results for critical volume and concentration similar to previous work. The influence of experimental procedures and methods for data development are considered. The basic theoretical derivation developed was found to provide a basis for predicting the approximate nonspecific toxicity of nondegradable lipophilic organic compounds at different exposure time periods. This requires a knowledge of the Kow value and the clearance rate constant (k2) which can be calculated from the Kow value."} {"id": "PMID:1282871", "title": "Protective effect of zinc on heme biosynthesis disturbances in rabbits after administration per os of tin.", "content": "In the present study the lowest p.o. doses of tin affecting heme biosynthesis in rabbits were determined and the protective effect of zinc on these disorders was evaluated. The experiment was performed on female rabbits who received per os single doses of SnCl2 x 2 H2O (10, 100, and 200 mg Sn/kg) and ZnSO4 (50 mg Zn/kg s.c.). The activities of delta-aminolevulinic acid dehydratase (ALA-D) in the whole blood, free erythrocyte propoporhyrins, urine delta-aminolevulinic acid, and coproporphyrins (CP-U) were determined. In animals administered tin at a dose of 100 mg Sn/kg, ALA-D activity decreased by about 80% and two- to threefold increases in the ALA and CP concentrations in urine were observed. A protective effect of zinc with respect to ALA-D activity was noticed in both groups (100 and 200 mg Sn/kg) after combined administration of both metals. Results of an interaction between zinc and tin were also observed to reduce ALA levels in urine, whereas zinc did not protect against an effect of tin on CP excretion.", "contents": "Protective effect of zinc on heme biosynthesis disturbances in rabbits after administration per os of tin. In the present study the lowest p.o. doses of tin affecting heme biosynthesis in rabbits were determined and the protective effect of zinc on these disorders was evaluated. The experiment was performed on female rabbits who received per os single doses of SnCl2 x 2 H2O (10, 100, and 200 mg Sn/kg) and ZnSO4 (50 mg Zn/kg s.c.). The activities of delta-aminolevulinic acid dehydratase (ALA-D) in the whole blood, free erythrocyte propoporhyrins, urine delta-aminolevulinic acid, and coproporphyrins (CP-U) were determined. In animals administered tin at a dose of 100 mg Sn/kg, ALA-D activity decreased by about 80% and two- to threefold increases in the ALA and CP concentrations in urine were observed. A protective effect of zinc with respect to ALA-D activity was noticed in both groups (100 and 200 mg Sn/kg) after combined administration of both metals. Results of an interaction between zinc and tin were also observed to reduce ALA levels in urine, whereas zinc did not protect against an effect of tin on CP excretion."} {"id": "PMID:1282872", "title": "The absorption of hydrophobic chemicals across perfused rainbow trout gills: methodological aspects.", "content": "The absorption rates of 4-bromophenol, 2,4-dibromophenol, 3,4,5-trichloroguaiacol, and tetrachloroveratrol across fish gill epithelium have been measured in a perfused gill preparation from rainbow trout (Oncorhynchus mykiss). In additional experiments the absorption rate of tetrachloroveratrol was measured in free swimming fish. The absorption rates were perfusion limited in gills perfused with a saline containing 2% polyvinylpyrrolidone MW 40,000 (PVP-40) as a plasma protein substitute. Replacement of PVP-40 with 2% bovine serum albumin increased the absorption rates 5-10 times, and in this case rates were not perfusion limited. Furthermore, they were not ventilation limited at ventilatory water flow rates between 0.45 and 1.5 liter/(min 100 g). Our observations suggest that the absorption rates in the presence of albumin are limited by diffusion in the epithelial cell layers. The rates measured in the perfused gills are in close agreement with those measured in vivo. We conclude that the preparation is well suited to investigate the mechanisms behind the absorption of hydrophobic compounds across fish gills and how the absorption rate is related to the physicochemical properties of the compounds, as well as to environmental factors.", "contents": "The absorption of hydrophobic chemicals across perfused rainbow trout gills: methodological aspects. The absorption rates of 4-bromophenol, 2,4-dibromophenol, 3,4,5-trichloroguaiacol, and tetrachloroveratrol across fish gill epithelium have been measured in a perfused gill preparation from rainbow trout (Oncorhynchus mykiss). In additional experiments the absorption rate of tetrachloroveratrol was measured in free swimming fish. The absorption rates were perfusion limited in gills perfused with a saline containing 2% polyvinylpyrrolidone MW 40,000 (PVP-40) as a plasma protein substitute. Replacement of PVP-40 with 2% bovine serum albumin increased the absorption rates 5-10 times, and in this case rates were not perfusion limited. Furthermore, they were not ventilation limited at ventilatory water flow rates between 0.45 and 1.5 liter/(min 100 g). Our observations suggest that the absorption rates in the presence of albumin are limited by diffusion in the epithelial cell layers. The rates measured in the perfused gills are in close agreement with those measured in vivo. We conclude that the preparation is well suited to investigate the mechanisms behind the absorption of hydrophobic compounds across fish gills and how the absorption rate is related to the physicochemical properties of the compounds, as well as to environmental factors."} {"id": "PMID:1282873", "title": "Nephrotoxic and hepatotoxic effects of trivalent and hexavalent chromium in a teleost fish Anabas scandens: enzymological and biochemical changes.", "content": "The effects of trivalent and hexavalent chromium (Cr3+ and Cr6+) compounds on renal and hepatic respiratory enzymes and metabolites of a freshwater fish, Anabas scandens, were studied. In a subchronic exposure of 30 days, both forms of chromium inhibited the activities of lactate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase, whereas the hexavalent form induced greater effects. The levels of pyruvate and lactate are not exactly reflected in lactate dehydrogenase activity.", "contents": "Nephrotoxic and hepatotoxic effects of trivalent and hexavalent chromium in a teleost fish Anabas scandens: enzymological and biochemical changes. The effects of trivalent and hexavalent chromium (Cr3+ and Cr6+) compounds on renal and hepatic respiratory enzymes and metabolites of a freshwater fish, Anabas scandens, were studied. In a subchronic exposure of 30 days, both forms of chromium inhibited the activities of lactate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, and isocitrate dehydrogenase, whereas the hexavalent form induced greater effects. The levels of pyruvate and lactate are not exactly reflected in lactate dehydrogenase activity."} {"id": "PMID:1282874", "title": "Study of the interactions between copper, cadmium, and ferbam using the protozoan Colpidium campylum bioassay.", "content": "The toxicity of a copper-cadmium-ferbam mixture has been studied using the protozoan Colpidium campylum bioassay. The assays were designed according to the factorial experiments method, associated with multiple regression analysis. The results show that, at the concentrations tested, a synergy occurs between cadmium and ferbam, whereas the copper is only oligodynamic.", "contents": "Study of the interactions between copper, cadmium, and ferbam using the protozoan Colpidium campylum bioassay. The toxicity of a copper-cadmium-ferbam mixture has been studied using the protozoan Colpidium campylum bioassay. The assays were designed according to the factorial experiments method, associated with multiple regression analysis. The results show that, at the concentrations tested, a synergy occurs between cadmium and ferbam, whereas the copper is only oligodynamic."} {"id": "PMID:1282875", "title": "Whole-body arsenic concentrations in rainbow trout during acute exposure to arsenate.", "content": "This research explored the influence of temperature and waterborne arsenate exposure level on the whole-body arsenic (As) concentration in rainbow trout (Oncorhynchus mykiss) at loss of equilibrium (LOE), an acute toxicity endpoint. The mean median times (ET50s) to LOE for fish exposed to 120 mg arsenate liter-1 at 5 degrees C, as well as 60 and 120 mg liter-1 at 15 degrees C were 56.8, 210, and 34.8 hr, respectively. Despite the differences in ET50, the fish showed respective mean (SE) whole-body As concentrations of 8.6 (0.3), 8.1 (0.6), and 8.6 (0.4) micrograms As g-1, values which were not significantly different. Fish exposed to 240 mg arsenate liter-1 at 5 degrees C, which had a LOE ET50 of 32.2 hr, were observed to have a mean (SE) whole-body arsenic concentration of 13.5 micrograms g-1, significantly higher than the levels in fish from all other treatments. A 3-hr delay between LOE and sampling did not significantly alter whole-body As concentration. The results are discussed in terms of the utility of using whole-body As concentrations to interpret the impacts of arsenate on fish populations in the field.", "contents": "Whole-body arsenic concentrations in rainbow trout during acute exposure to arsenate. This research explored the influence of temperature and waterborne arsenate exposure level on the whole-body arsenic (As) concentration in rainbow trout (Oncorhynchus mykiss) at loss of equilibrium (LOE), an acute toxicity endpoint. The mean median times (ET50s) to LOE for fish exposed to 120 mg arsenate liter-1 at 5 degrees C, as well as 60 and 120 mg liter-1 at 15 degrees C were 56.8, 210, and 34.8 hr, respectively. Despite the differences in ET50, the fish showed respective mean (SE) whole-body As concentrations of 8.6 (0.3), 8.1 (0.6), and 8.6 (0.4) micrograms As g-1, values which were not significantly different. Fish exposed to 240 mg arsenate liter-1 at 5 degrees C, which had a LOE ET50 of 32.2 hr, were observed to have a mean (SE) whole-body arsenic concentration of 13.5 micrograms g-1, significantly higher than the levels in fish from all other treatments. A 3-hr delay between LOE and sampling did not significantly alter whole-body As concentration. The results are discussed in terms of the utility of using whole-body As concentrations to interpret the impacts of arsenate on fish populations in the field."} {"id": "PMID:1282876", "title": "Toxicokinetics of 2,2',4,4'- and 3,3',4,4'-tetrachlorobiphenyl congeners in the house cricket.", "content": "Recently, investigators have reported bioaccumulation of polychlorinated biphenyls (PCBs) in insects collected at hazardous waste sites. Little is known about differences in bioaccumulation of particular PCB congeners in insects. The authors report on the toxicokinetics of a non-coplanar ortho substituted congener, 2,2',4,4'-tetrachlorobiphenyl (PCB-47) and a coplanar non-ortho substituted PCB, 3,3',4,4'-tetrachlorobiphenyl (PCB-77) in topically treated house crickets. Penetration and excretion were more rapid for PCB-47 than for PCB-77. PCB-47 demonstrated a high affinity for abdomen, gut, and gonads, whereas, PCB-77 had a greater affinity for the head and thorax. Sex differences were observed in excretion and distribution. Females had an increased excretion of PCBs and increased accumulation in gut and gonads compared to males. Differences in lipophilicity can explain differences in distribution between sexes and of compounds within sexes. However, to explain the observed difference in penetration, it is necessary to invoke explanations based on stearic factors associated with coplanarity of the molecules. Differences in excretion are likely related to sex differences in mixed-function oxidase activities. These toxicokinetic data suggest that the more toxic coplanar congener, PCB-77, is likely to be more persistent in crickets compared to PCB-47, despite its lower lipophilicity.", "contents": "Toxicokinetics of 2,2',4,4'- and 3,3',4,4'-tetrachlorobiphenyl congeners in the house cricket. Recently, investigators have reported bioaccumulation of polychlorinated biphenyls (PCBs) in insects collected at hazardous waste sites. Little is known about differences in bioaccumulation of particular PCB congeners in insects. The authors report on the toxicokinetics of a non-coplanar ortho substituted congener, 2,2',4,4'-tetrachlorobiphenyl (PCB-47) and a coplanar non-ortho substituted PCB, 3,3',4,4'-tetrachlorobiphenyl (PCB-77) in topically treated house crickets. Penetration and excretion were more rapid for PCB-47 than for PCB-77. PCB-47 demonstrated a high affinity for abdomen, gut, and gonads, whereas, PCB-77 had a greater affinity for the head and thorax. Sex differences were observed in excretion and distribution. Females had an increased excretion of PCBs and increased accumulation in gut and gonads compared to males. Differences in lipophilicity can explain differences in distribution between sexes and of compounds within sexes. However, to explain the observed difference in penetration, it is necessary to invoke explanations based on stearic factors associated with coplanarity of the molecules. Differences in excretion are likely related to sex differences in mixed-function oxidase activities. These toxicokinetic data suggest that the more toxic coplanar congener, PCB-77, is likely to be more persistent in crickets compared to PCB-47, despite its lower lipophilicity."} {"id": "PMID:1282877", "title": "Simple method to prolong the closed bottle test for the determination of the inherent biodegradability.", "content": "A method to prolong the closed bottle test up to 200 days is described and validated. This prolonged closed bottle test has been used to determine the biodegradability of \"recalcitrant\" and toxic organic compounds. The results obtained in the prolonged closed bottle test are in accordance with those mentioned in the literature on biodegradation of organic compounds in waste water purification plants and on the isolation of microorganisms capable of utilizing these compounds as carbon and energy source. Furthermore, this test may prevent discrepancies and unexplainable results obtained in a 28-day test. The test has the potential to be used as an inherent biodegradability test when recognized by the authorities.", "contents": "Simple method to prolong the closed bottle test for the determination of the inherent biodegradability. A method to prolong the closed bottle test up to 200 days is described and validated. This prolonged closed bottle test has been used to determine the biodegradability of \"recalcitrant\" and toxic organic compounds. The results obtained in the prolonged closed bottle test are in accordance with those mentioned in the literature on biodegradation of organic compounds in waste water purification plants and on the isolation of microorganisms capable of utilizing these compounds as carbon and energy source. Furthermore, this test may prevent discrepancies and unexplainable results obtained in a 28-day test. The test has the potential to be used as an inherent biodegradability test when recognized by the authorities."} {"id": "PMID:1282878", "title": "Individual and combined cytotoxic effects of cadmium, copper, and nickel on brown cells of Mercenaria mercenaria.", "content": "An assay based on the lysosomal incorporation of neutral red dye by brown cells of Mercenaria mercenaria (Bivalvia) was used to measure the cytotoxicity of Cd2+, Cu2+, and Ni2+ singly and in combination. Cytotoxicity was a linear function of Cd2+ concentration 0.1-1.5 mM and Cu2+ concentration between 10 and 100 microM. Nickel was not cytotoxic at concentrations as high as 10 mM. The presence of Cu2+ lessened the cytotoxic effect of Cd2+. Ni2+ did not affect cytotoxicity in combination with either Cu2+ or Cd2+.Ni2+ inflated estimates of cell survival by the neutral red assay in this study. Cells exposed to Ni2+ yielded measured quantities of neutral red dye in excess of those measured in cells from control treatments.", "contents": "Individual and combined cytotoxic effects of cadmium, copper, and nickel on brown cells of Mercenaria mercenaria. An assay based on the lysosomal incorporation of neutral red dye by brown cells of Mercenaria mercenaria (Bivalvia) was used to measure the cytotoxicity of Cd2+, Cu2+, and Ni2+ singly and in combination. Cytotoxicity was a linear function of Cd2+ concentration 0.1-1.5 mM and Cu2+ concentration between 10 and 100 microM. Nickel was not cytotoxic at concentrations as high as 10 mM. The presence of Cu2+ lessened the cytotoxic effect of Cd2+. Ni2+ did not affect cytotoxicity in combination with either Cu2+ or Cd2+.Ni2+ inflated estimates of cell survival by the neutral red assay in this study. Cells exposed to Ni2+ yielded measured quantities of neutral red dye in excess of those measured in cells from control treatments."} {"id": "PMID:1282879", "title": "The effects of agitation, sediment, and competition on the persistence and efficacy of Bacillus thuringiensis var. israelensis (Bti).", "content": "The persistence and efficacy of Bacillus thuringiensis var. israelensis (Bti) were examined in aquatic microcosms under varying conditions of agitation, sediment content, and microbial competition. Agitation was found to be the most important factor in maintaining persistence of Bti cells and the bioavailability of Bti toxin. Sediment acted to decrease efficacy by increasing settling of the toxic particles, but did not decrease the persistence of Bti cells were found, but efficacy of the Bti endotoxin was adversely affected.", "contents": "The effects of agitation, sediment, and competition on the persistence and efficacy of Bacillus thuringiensis var. israelensis (Bti). The persistence and efficacy of Bacillus thuringiensis var. israelensis (Bti) were examined in aquatic microcosms under varying conditions of agitation, sediment content, and microbial competition. Agitation was found to be the most important factor in maintaining persistence of Bti cells and the bioavailability of Bti toxin. Sediment acted to decrease efficacy by increasing settling of the toxic particles, but did not decrease the persistence of Bti cells were found, but efficacy of the Bti endotoxin was adversely affected."} {"id": "PMID:1282880", "title": "Responses of fish populations and communities to pulp mill effluents: a holistic assessment.", "content": "Fish populations residing in a river receiving bleached kraft mill effluents (BKME) and in an uncontaminated river were investigated to evaluate causal relationships between exposure to BKME and various indicators of fish health. The Index of Biotic Integrity demonstrated that species richness and composition were much lower in the contaminated river with an obvious imbalance in the trophic structure of the fish community. Biomolecular and biochemical responses such as DNA damage and elevated activity of detoxification enzymes indicated that fish in the contaminated river had been exposed to toxicants. The status of various condition indices such as the liver and visceral somatic indices suggested metabolic and nutritional imbalances in sunfish as a result of exposure to pulp mill effluents. Fish populations in the contaminated river also demonstrated an abnormal size distribution and age structure. Female redbreast sunfish from the BKME-impacted river contained a large number of atretic oocytes and had lower serum levels of estradiol than fish from the reference site. These observations plus data from previous developmental toxicity studies suggest that the primary mechanism by which BKME may affect fish populations in this river is through reproductive dysfunction and recruitment failure. Decreased recruitment may have caused a reduction in population size and resulted in decreased competition and increased resource availability. With increased food and habitat availability, more energy may have been available for growth and lipid storage of survivors in the contaminated river.", "contents": "Responses of fish populations and communities to pulp mill effluents: a holistic assessment. Fish populations residing in a river receiving bleached kraft mill effluents (BKME) and in an uncontaminated river were investigated to evaluate causal relationships between exposure to BKME and various indicators of fish health. The Index of Biotic Integrity demonstrated that species richness and composition were much lower in the contaminated river with an obvious imbalance in the trophic structure of the fish community. Biomolecular and biochemical responses such as DNA damage and elevated activity of detoxification enzymes indicated that fish in the contaminated river had been exposed to toxicants. The status of various condition indices such as the liver and visceral somatic indices suggested metabolic and nutritional imbalances in sunfish as a result of exposure to pulp mill effluents. Fish populations in the contaminated river also demonstrated an abnormal size distribution and age structure. Female redbreast sunfish from the BKME-impacted river contained a large number of atretic oocytes and had lower serum levels of estradiol than fish from the reference site. These observations plus data from previous developmental toxicity studies suggest that the primary mechanism by which BKME may affect fish populations in this river is through reproductive dysfunction and recruitment failure. Decreased recruitment may have caused a reduction in population size and resulted in decreased competition and increased resource availability. With increased food and habitat availability, more energy may have been available for growth and lipid storage of survivors in the contaminated river."} {"id": "PMID:1282881", "title": "Predictions of the secondary structure and antigenicity of human and bovine tropoelastins.", "content": "Secondary structure and antigenicity predictive methods have been applied to the sequences of human and bovine tropoelastins in order to have some insight into the molecular structure of its insoluble counterpart, i.e., elastin. For both tropoelastins, all the predictions yielded 11 major regions, in which the pleated conformation was predominant, separated by 10 strong helical segments of various lengths located within alanyl rich regions of the chains. The overall conformations of human and bovine tropoelastins were estimated to contain 18 +/- 5% alpha-helices, 63 +/- 17% beta-sheets, 13 +/- 13% beta-turns and 6 +/- 6% random coil. For both tropoelastins, antigenicity predictions indicated the presence of seven synthetic decapeptides corresponding to continuous linear epitopes of the molecule. Some of the predicted epitopes are located in the same regions in both species while others are not. These predictions have allowed us to propose an alpha/beta conformation for tropoelastin. Therefore this extracellular matrix macromolecule might be more structured (10 helical segments for about 18% of the overall structure) than previously suggested.", "contents": "Predictions of the secondary structure and antigenicity of human and bovine tropoelastins. Secondary structure and antigenicity predictive methods have been applied to the sequences of human and bovine tropoelastins in order to have some insight into the molecular structure of its insoluble counterpart, i.e., elastin. For both tropoelastins, all the predictions yielded 11 major regions, in which the pleated conformation was predominant, separated by 10 strong helical segments of various lengths located within alanyl rich regions of the chains. The overall conformations of human and bovine tropoelastins were estimated to contain 18 +/- 5% alpha-helices, 63 +/- 17% beta-sheets, 13 +/- 13% beta-turns and 6 +/- 6% random coil. For both tropoelastins, antigenicity predictions indicated the presence of seven synthetic decapeptides corresponding to continuous linear epitopes of the molecule. Some of the predicted epitopes are located in the same regions in both species while others are not. These predictions have allowed us to propose an alpha/beta conformation for tropoelastin. Therefore this extracellular matrix macromolecule might be more structured (10 helical segments for about 18% of the overall structure) than previously suggested."} {"id": "PMID:1282882", "title": "Genetic polymorphism of apolipoprotein H (beta 2-glycoprotein I) in African blacks from the Ivory Coast.", "content": "The apolipoprotein H (APO H) polymorphism was analyzed in the Negroid population from the Ivory Coast using polyacrylamide gel isoelectric focusing, followed by immunoblotting. The gene frequencies of alleles APO H*1, APO H*2, APO H*3 and APO H*4 were calculated to be 0.012, 0.921, 0.047, and 0.020, respectively. The assumption that APO H*4 represents a Negroid marker allele is supported by this population study.", "contents": "Genetic polymorphism of apolipoprotein H (beta 2-glycoprotein I) in African blacks from the Ivory Coast. The apolipoprotein H (APO H) polymorphism was analyzed in the Negroid population from the Ivory Coast using polyacrylamide gel isoelectric focusing, followed by immunoblotting. The gene frequencies of alleles APO H*1, APO H*2, APO H*3 and APO H*4 were calculated to be 0.012, 0.921, 0.047, and 0.020, respectively. The assumption that APO H*4 represents a Negroid marker allele is supported by this population study."} {"id": "PMID:1282883", "title": "Recovery of protein by coomassie brilliant blue precipitation prior to electrophoresis.", "content": "The interaction of protein with Coomassie Brilliant Blue G-250 results in formation of an insoluble protein-dye complex which can be recovered by centrifugation and redissolved for electrophoretic analysis. The precipitated protein can be washed in acetone to remove excess dye in order to enhance resolution. The residual dye becomes dissociated from the proteins on electrophoresis and can be exploited as a \"dye front\". The method allows simultaneous protein assay and recovery of microgram amounts of protein from dilute solution and could be widely applied for conserving, concentrating and desalting minute amounts of valuable sample prior to electrophoretic analysis.", "contents": "Recovery of protein by coomassie brilliant blue precipitation prior to electrophoresis. The interaction of protein with Coomassie Brilliant Blue G-250 results in formation of an insoluble protein-dye complex which can be recovered by centrifugation and redissolved for electrophoretic analysis. The precipitated protein can be washed in acetone to remove excess dye in order to enhance resolution. The residual dye becomes dissociated from the proteins on electrophoresis and can be exploited as a \"dye front\". The method allows simultaneous protein assay and recovery of microgram amounts of protein from dilute solution and could be widely applied for conserving, concentrating and desalting minute amounts of valuable sample prior to electrophoretic analysis."} {"id": "PMID:1282884", "title": "Fatty-acid-binding protein in locust flight muscle. Developmental changes of expression, concentration and intracellular distribution.", "content": "Fatty-acid-binding protein (FABP) from the flight muscle of the locust, Schistocerca gregaria, is similar to mammalian heart FABP in its primary structure and biochemical characteristics. We have studied developmental changes using enzyme-linked immunosorbent assays, RNA hybridization and electron microscopy of immunogold-labeled sections. Locust muscle FABP is the most abundant soluble muscle protein in fully developed adult locusts, comprising 18% of the total cytosolic protein. At the beginning of the adult stage, however, no FABP is detectable. Its concentration rises during the following 10 days, after which it reaches its maximal value. FABP mRNA is present shortly after adult ecdysis; its concentration increases for 10 days, before it diminishes and reaches a constant, low level, probably needed to maintain the established FABP level. The protein is abundant in cytosol and nuclei, but virtually absent in mitochondria.", "contents": "Fatty-acid-binding protein in locust flight muscle. Developmental changes of expression, concentration and intracellular distribution. Fatty-acid-binding protein (FABP) from the flight muscle of the locust, Schistocerca gregaria, is similar to mammalian heart FABP in its primary structure and biochemical characteristics. We have studied developmental changes using enzyme-linked immunosorbent assays, RNA hybridization and electron microscopy of immunogold-labeled sections. Locust muscle FABP is the most abundant soluble muscle protein in fully developed adult locusts, comprising 18% of the total cytosolic protein. At the beginning of the adult stage, however, no FABP is detectable. Its concentration rises during the following 10 days, after which it reaches its maximal value. FABP mRNA is present shortly after adult ecdysis; its concentration increases for 10 days, before it diminishes and reaches a constant, low level, probably needed to maintain the established FABP level. The protein is abundant in cytosol and nuclei, but virtually absent in mitochondria."} {"id": "PMID:1282885", "title": "Dominant role of glucagon in the initial induction of phosphoenolpyruvate carboxykinase mRNA in cultured hepatocytes from fetal rats.", "content": "The injection of streptozotocin to 18-day-old rat fetuses induced, 2 days later, a 50% fall in plasma insulin and a twofold increase in plasma glucagon concentrations and liver cAMP levels. Phosphoenolpyruvate carboxykinase mRNA that were undetectable in the fetal rat liver, accumulated 48 h after streptozotocin injection, their concentration being 30% of that found in the liver of 1-day-old newborn rats in whom liver phosphoenolpyruvate carboxykinase gene expression is maximal. Physiological concentrations of glucagon (0.7 +/- 0.2 nM) induced, within 2 h, phosphoenolpyruvate carboxykinase mRNA accumulation in cultured hepatocytes from 20-day-old fetuses. The addition of insulin (0.01-100 nM) inhibits, by no more than 30%, the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation. Exposure of fetal hepatocytes to insulin for 24 h did not change the glucagon dose/response curve and did not lead to a more efficient inhibition of the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation, despite a clear stimulatory effect on the rate of lipogenesis. In contrast, when hepatocytes were cultured in the presence of dexamethasone, the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation can be totally inhibited by pharmacological concentrations of insulin (10 nM). From these in-vivo and in-vitro studies, it is concluded that, under physiological conditions, the postnatal rise in plasma glucagon concentration is more important than the fall in the plasma insulin concentration for the primary induction of liver phosphoenolpyruvate carboxykinase gene expression.", "contents": "Dominant role of glucagon in the initial induction of phosphoenolpyruvate carboxykinase mRNA in cultured hepatocytes from fetal rats. The injection of streptozotocin to 18-day-old rat fetuses induced, 2 days later, a 50% fall in plasma insulin and a twofold increase in plasma glucagon concentrations and liver cAMP levels. Phosphoenolpyruvate carboxykinase mRNA that were undetectable in the fetal rat liver, accumulated 48 h after streptozotocin injection, their concentration being 30% of that found in the liver of 1-day-old newborn rats in whom liver phosphoenolpyruvate carboxykinase gene expression is maximal. Physiological concentrations of glucagon (0.7 +/- 0.2 nM) induced, within 2 h, phosphoenolpyruvate carboxykinase mRNA accumulation in cultured hepatocytes from 20-day-old fetuses. The addition of insulin (0.01-100 nM) inhibits, by no more than 30%, the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation. Exposure of fetal hepatocytes to insulin for 24 h did not change the glucagon dose/response curve and did not lead to a more efficient inhibition of the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation, despite a clear stimulatory effect on the rate of lipogenesis. In contrast, when hepatocytes were cultured in the presence of dexamethasone, the glucagon-induced phosphoenolpyruvate carboxykinase mRNA accumulation can be totally inhibited by pharmacological concentrations of insulin (10 nM). From these in-vivo and in-vitro studies, it is concluded that, under physiological conditions, the postnatal rise in plasma glucagon concentration is more important than the fall in the plasma insulin concentration for the primary induction of liver phosphoenolpyruvate carboxykinase gene expression."} {"id": "PMID:1282886", "title": "Differences in the proteinase inhibition mechanism of human alpha 2-macroglobulin and pregnancy zone protein.", "content": "Different conformational states of human alpha 2-macroglobulin (alpha 2M) and pregnancy zone protein (PZP) were investigated following modifications of the functional sites, i.e. the 'bait' regions and the thiol esters, by use of chymotrypsin, methylamine and dinitrophenylthiocyanate. Gel electrophoresis, mAb (7H11D6 and alpha 1:1) and in vivo plasma clearance were used to describe different molecular states in the proteinase inhibitors. In alpha 2M, in which the thiol ester is broken by binding of methylamine and the 'trap' is closed, cyanylation of the liberated thiol group from the thiol ester modulates reopening of the 'trap' and the 'bait' regions become available for cleavage again. The trapping of proteinases in the cyanylated derivative indicates that the trap functions as in native alpha 2M. In contrast, cyanylation has no effect on proteinase-treated alpha 2M. As demonstrated by binding to mAb, the methylamine and dinitrophenylthiocyanate-treated alpha 2M exposes the receptor-recognition site, but the derivative is not cleared from the circulation in mice. The trap is not functional in PZP. In native PZP and PZP treated with methylamine, the conformational states seem similar. The receptor-recognition sites are not exposed and removal from the circulation in vivo is not seen for these as for the PZP-chymotrypsin complex. Tetramers are only formed when proteinases can be covalently bound to the PZP. Conformational changes are not detected in PZP derivatives in which the thiol ester is treated with methylamine and dinitrophenylthiocyanate. The results suggest that the conformational changes in alpha 2M are generated by mechanisms different to these in PZP. The key structure gearing the conformational changes in alpha 2M is the thiol ester, by which the events 'trapping' and exposure of the receptor-recognition site can be separated. In PZP, the crucial step for the conformational changes is the cleavage of the 'bait' region, since cleavage of the thiol ester does not lead to any detectable conformational changes by the methods used.", "contents": "Differences in the proteinase inhibition mechanism of human alpha 2-macroglobulin and pregnancy zone protein. Different conformational states of human alpha 2-macroglobulin (alpha 2M) and pregnancy zone protein (PZP) were investigated following modifications of the functional sites, i.e. the 'bait' regions and the thiol esters, by use of chymotrypsin, methylamine and dinitrophenylthiocyanate. Gel electrophoresis, mAb (7H11D6 and alpha 1:1) and in vivo plasma clearance were used to describe different molecular states in the proteinase inhibitors. In alpha 2M, in which the thiol ester is broken by binding of methylamine and the 'trap' is closed, cyanylation of the liberated thiol group from the thiol ester modulates reopening of the 'trap' and the 'bait' regions become available for cleavage again. The trapping of proteinases in the cyanylated derivative indicates that the trap functions as in native alpha 2M. In contrast, cyanylation has no effect on proteinase-treated alpha 2M. As demonstrated by binding to mAb, the methylamine and dinitrophenylthiocyanate-treated alpha 2M exposes the receptor-recognition site, but the derivative is not cleared from the circulation in mice. The trap is not functional in PZP. In native PZP and PZP treated with methylamine, the conformational states seem similar. The receptor-recognition sites are not exposed and removal from the circulation in vivo is not seen for these as for the PZP-chymotrypsin complex. Tetramers are only formed when proteinases can be covalently bound to the PZP. Conformational changes are not detected in PZP derivatives in which the thiol ester is treated with methylamine and dinitrophenylthiocyanate. The results suggest that the conformational changes in alpha 2M are generated by mechanisms different to these in PZP. The key structure gearing the conformational changes in alpha 2M is the thiol ester, by which the events 'trapping' and exposure of the receptor-recognition site can be separated. In PZP, the crucial step for the conformational changes is the cleavage of the 'bait' region, since cleavage of the thiol ester does not lead to any detectable conformational changes by the methods used."} {"id": "PMID:1282887", "title": "A mutant of human insulin-like growth factor II (IGF II) with the processing sites of proinsulin. Expression and binding studies of processed IGF II.", "content": "A mutant of human insulin-like growth factor II (IGF II) was constructed by site-directed mutagenesis: the nucleotides coding for Ser33 and Ser39 were changed to yield Arg and Lys, respectively, thus creating two pairs of basic residues, Arg-Arg and Lys-Arg, as flanking sequences of the remaining C domain. [Arg33, Lys39]IGF II was expressed in NIH-3T3 cells as a processed two-chain peptide with a deletion of amino acid residues 37-40 and crosslinked by three disulfide bonds. This des(37-40)[Arg33]IGF II showed 3.6-fold and 7.4-fold reduced affinities to the type 1 and type 2 IGF receptor overexpressing cells, respectively, whereas the thymidine incorporation potency was the same as that of wild-type IGF II. We speculate that the discrepancy between the reduced binding to the type 1 IGF receptor and the full thymidine incorporation potency is due to the 6.1-fold reduced affinity of the expressed mutant to the co-expressed IGF binding protein 3 (IGFBP-3). The results suggest that des(37-40)[Arg33]IGF II assumes a conformation very similar to IGF II, and that the entire length of the C domain is not essential for biological activity.", "contents": "A mutant of human insulin-like growth factor II (IGF II) with the processing sites of proinsulin. Expression and binding studies of processed IGF II. A mutant of human insulin-like growth factor II (IGF II) was constructed by site-directed mutagenesis: the nucleotides coding for Ser33 and Ser39 were changed to yield Arg and Lys, respectively, thus creating two pairs of basic residues, Arg-Arg and Lys-Arg, as flanking sequences of the remaining C domain. [Arg33, Lys39]IGF II was expressed in NIH-3T3 cells as a processed two-chain peptide with a deletion of amino acid residues 37-40 and crosslinked by three disulfide bonds. This des(37-40)[Arg33]IGF II showed 3.6-fold and 7.4-fold reduced affinities to the type 1 and type 2 IGF receptor overexpressing cells, respectively, whereas the thymidine incorporation potency was the same as that of wild-type IGF II. We speculate that the discrepancy between the reduced binding to the type 1 IGF receptor and the full thymidine incorporation potency is due to the 6.1-fold reduced affinity of the expressed mutant to the co-expressed IGF binding protein 3 (IGFBP-3). The results suggest that des(37-40)[Arg33]IGF II assumes a conformation very similar to IGF II, and that the entire length of the C domain is not essential for biological activity."} {"id": "PMID:1282888", "title": "A novel calcium-binding protein from Euglena gracilis. Characterisation of a cDNA encoding a 74-kDa acidic-repeat protein targeted across the endoplasmic reticulum.", "content": "We have isolated a novel cDNA from Euglena gracilis that encodes a protein composed of 24.9% aspartate with an estimated pI of 3.56, and a deduced molecular mass of 73,542 Da. The first 20 or so amino acids are hydrophobic and resemble a signal sequence. The rest of the polypeptide is composed of a 23-amino-acid repeat. There are 30 repeats, of which 23 are full length. Part of the consensus sequence derived from the repeats has some similarity to the loop of the EF-hand type calcium-binding motif. Evidence is presented that a fusion protein of this novel protein with beta-galactosidase can bind calcium. Northern blotting indicates a single transcript of 2.3 kb (the same size as the cDNA). In-vitro translation of the cDNA gives a protein that migrates on SDS/PAGE with an apparent molecular mass of 120-125 kDa. The protein is processed into a smaller, protease-protected form (110-120 kDa) when translated in the presence of canine pancreatic microsomal vesicles. This suggests that the protein is targeted across the endoplasmic reticulum membrane in vivo, and is the first report of a signal sequence from E. gracilis. We propose that the cDNA obtained encodes a novel calcium-binding protein that is either secreted or resident in the endomembrane system of E. gracilis, and call it the acidic-repeat protein.", "contents": "A novel calcium-binding protein from Euglena gracilis. Characterisation of a cDNA encoding a 74-kDa acidic-repeat protein targeted across the endoplasmic reticulum. We have isolated a novel cDNA from Euglena gracilis that encodes a protein composed of 24.9% aspartate with an estimated pI of 3.56, and a deduced molecular mass of 73,542 Da. The first 20 or so amino acids are hydrophobic and resemble a signal sequence. The rest of the polypeptide is composed of a 23-amino-acid repeat. There are 30 repeats, of which 23 are full length. Part of the consensus sequence derived from the repeats has some similarity to the loop of the EF-hand type calcium-binding motif. Evidence is presented that a fusion protein of this novel protein with beta-galactosidase can bind calcium. Northern blotting indicates a single transcript of 2.3 kb (the same size as the cDNA). In-vitro translation of the cDNA gives a protein that migrates on SDS/PAGE with an apparent molecular mass of 120-125 kDa. The protein is processed into a smaller, protease-protected form (110-120 kDa) when translated in the presence of canine pancreatic microsomal vesicles. This suggests that the protein is targeted across the endoplasmic reticulum membrane in vivo, and is the first report of a signal sequence from E. gracilis. We propose that the cDNA obtained encodes a novel calcium-binding protein that is either secreted or resident in the endomembrane system of E. gracilis, and call it the acidic-repeat protein."} {"id": "PMID:1282889", "title": "Albumin binding in uraemia: quantitative assessment of inhibition by endogenous ligands and carbamylation of albumin.", "content": "The binding capacity of human serum albumin (HSA) for small acidic molecules is known to be reduced in chronic renal failure (CRF). The contribution of competitive inhibition by accumulated endogenous ligands and of structural changes in HSA has now been evaluated. In a fluorimetric in vitro assay using HSA and two dansylated amino acids the inhibitory properties of various endogenous ligands were determined in concentration-effect studies. The effect of carbamylation of HSA on binding was also examined. The mode of inhibition, including binding parameters n and Ka, was determined. Finally, HSA binding in sera from controls and dialysis patients was compared in a modified assay. Thirty three substances were tested and were placed in 3 groups: strong inhibitors (IC50 < 3*10(-5) mol.l-1, e.g. indolyl acids, furanoic acids), medium inhibitors (IC50 > 3*10(-5), eg. vanillic acid), and no inhibition (e.g. urea, creatinine, guanidino compounds). Complete (> 80%) carbamylation of HSA reduced binding by 67% in a non-competitive mode. There was a significant reduction in the binding capacity of HSA from the dialysis patients (approximately 24%), irrespective of medication. It is concluded that the uraemic binding defect of HSA is caused by competitive inhibition by the many physiological ligands accumulated in CRF and structural modifications of HSA. The assay presented proved useful for the rapid analysis of possible HSA binding inhibitors and for testing large groups of patients, e.g. comparison of dialysis treatments, and pharmacological binding studies.", "contents": "Albumin binding in uraemia: quantitative assessment of inhibition by endogenous ligands and carbamylation of albumin. The binding capacity of human serum albumin (HSA) for small acidic molecules is known to be reduced in chronic renal failure (CRF). The contribution of competitive inhibition by accumulated endogenous ligands and of structural changes in HSA has now been evaluated. In a fluorimetric in vitro assay using HSA and two dansylated amino acids the inhibitory properties of various endogenous ligands were determined in concentration-effect studies. The effect of carbamylation of HSA on binding was also examined. The mode of inhibition, including binding parameters n and Ka, was determined. Finally, HSA binding in sera from controls and dialysis patients was compared in a modified assay. Thirty three substances were tested and were placed in 3 groups: strong inhibitors (IC50 < 3*10(-5) mol.l-1, e.g. indolyl acids, furanoic acids), medium inhibitors (IC50 > 3*10(-5), eg. vanillic acid), and no inhibition (e.g. urea, creatinine, guanidino compounds). Complete (> 80%) carbamylation of HSA reduced binding by 67% in a non-competitive mode. There was a significant reduction in the binding capacity of HSA from the dialysis patients (approximately 24%), irrespective of medication. It is concluded that the uraemic binding defect of HSA is caused by competitive inhibition by the many physiological ligands accumulated in CRF and structural modifications of HSA. The assay presented proved useful for the rapid analysis of possible HSA binding inhibitors and for testing large groups of patients, e.g. comparison of dialysis treatments, and pharmacological binding studies."} {"id": "PMID:1282890", "title": "Corticocortical connections of cat primary somatosensory cortex.", "content": "The organization of corticocortical connections in the representation of the forepaw in cat primary somatosensory cortex (SI) was studied following injections of various tracers into different cortical cytoarchitectonic areas. Small injections of horseradish peroxidase, wheat germ agglutinin-conjugated HRP, Phaseolus vulgaris leukoagglutinin, or fast blue were placed into the representation of the forepaw in areas 3b, 1, or 2. The positions of labeled neurons in SI and the surrounding cortical areas were plotted on flattened surface reconstructions to determine the organization of the corticocortical connections within SI. A strong, reciprocal projection linked the two forepaw representations which have been described in area 3b and the part of area 2 which lies in the anterior bank of the lateral ansate sulcus (see Iwamura and Tanaka 1978a, b). Dense projections also linked these areas with SII, as previously reported (Burton and Kopf 1984a). Additional projections to area 3b arose primarily from areas 3a and 1. Projections to area 2 were more widespread than those to area 3b, and arose from all other areas of SI as well as from areas 4 and 5a. All injections into SI tended to label groups of neurons which lay in mediolateral strips. Corticocortical projection neurons which were most heavily labeled by SI injections were pyramidal cells in layer III. Additional projections from area 2 to 3b, area 5a to 2, and SII to areas 2 and 3b arose from layer VI as well. Although neurons of layers III and VI were always the most densely labeled, large injections into SI labeled neurons in layers II and V as well.", "contents": "Corticocortical connections of cat primary somatosensory cortex. The organization of corticocortical connections in the representation of the forepaw in cat primary somatosensory cortex (SI) was studied following injections of various tracers into different cortical cytoarchitectonic areas. Small injections of horseradish peroxidase, wheat germ agglutinin-conjugated HRP, Phaseolus vulgaris leukoagglutinin, or fast blue were placed into the representation of the forepaw in areas 3b, 1, or 2. The positions of labeled neurons in SI and the surrounding cortical areas were plotted on flattened surface reconstructions to determine the organization of the corticocortical connections within SI. A strong, reciprocal projection linked the two forepaw representations which have been described in area 3b and the part of area 2 which lies in the anterior bank of the lateral ansate sulcus (see Iwamura and Tanaka 1978a, b). Dense projections also linked these areas with SII, as previously reported (Burton and Kopf 1984a). Additional projections to area 3b arose primarily from areas 3a and 1. Projections to area 2 were more widespread than those to area 3b, and arose from all other areas of SI as well as from areas 4 and 5a. All injections into SI tended to label groups of neurons which lay in mediolateral strips. Corticocortical projection neurons which were most heavily labeled by SI injections were pyramidal cells in layer III. Additional projections from area 2 to 3b, area 5a to 2, and SII to areas 2 and 3b arose from layer VI as well. Although neurons of layers III and VI were always the most densely labeled, large injections into SI labeled neurons in layers II and V as well."} {"id": "PMID:1282891", "title": "Excitation of cutaneous afferent nerve endings in vitro by a combination of inflammatory mediators and conditioning effect of substance P.", "content": "A broad mixture of inflammatory mediators (\"inflammatory soup\") was used to investigate the responsiveness of primary afferents from rat hairy skin in an in vitro skin-saphenous nerve preparation. In addition, a conditioning effect of the tachykinin substance P on chemosensitivity of nociceptors was examined. Inflammatory soup (IS) was made up in synthetic interstitial fluid from bradykinin, serotonin, histamin and prostaglandin E2 (all 10(-5) M). In addition, the potassium and the hydrogen ion concentration (7 mM, pH 7.0) and the temperature (39.5 degrees C) were elevated. The latter agents, in a control solution, did not excite nociceptors (n = 5). IS was repeatedly superfused over the receptive fields for 5 min at 10 min intervals; substance P (SP 10(-6) and 10(-5) M) was applied during the last 5 min of the interval and during the subsequent IS stimulation. IS excited more than 80% of the mechano-heat sensitive (\"polymodal\") afferents with slowly conducting nerve fibres (n = 72), but none of the low-threshold mechanoreceptive slow and fast conducting units (n = 17). Slow conducting afferents with high mechanical threshold (n = 35) were weakly, and less frequently (< 20%), driven by IS. A majority, but not all, of the responsive units showed tachyphylaxis upon repeated IS application. None, however, lost its responsiveness completely. Conditioning heat stimulation (32-46.5 degrees C in 20 s) did not enhance the subsequent IS response, which may indicate that sensitizing substances normally released by a noxious heat stimulus were already contained in IS. No sensitization to mechanical (von Frey) or heat stimulation could be established in the period after the IS response had subsided and after the washout was completed, respectively. A short-lived sensitization may have been overlooked under these temporal restrictions. Conditioning SP in 10(-5) M but not in 10(-6) M concentration significantly increased the IS response of polymodal C fibres, by 58% on average (n = 14). SP did not excite the units. Comparing with previous data, we conclude that there is a significant synergism between inflammatory mediators, acting to induce more intense and more sustained discharge via many nociceptors than single mediators alone could achieve. Conditioning substance P can further enhance this algogenic action. Mechanisms of interaction and relative contributions of single substances remain to be elucidated.", "contents": "Excitation of cutaneous afferent nerve endings in vitro by a combination of inflammatory mediators and conditioning effect of substance P. A broad mixture of inflammatory mediators (\"inflammatory soup\") was used to investigate the responsiveness of primary afferents from rat hairy skin in an in vitro skin-saphenous nerve preparation. In addition, a conditioning effect of the tachykinin substance P on chemosensitivity of nociceptors was examined. Inflammatory soup (IS) was made up in synthetic interstitial fluid from bradykinin, serotonin, histamin and prostaglandin E2 (all 10(-5) M). In addition, the potassium and the hydrogen ion concentration (7 mM, pH 7.0) and the temperature (39.5 degrees C) were elevated. The latter agents, in a control solution, did not excite nociceptors (n = 5). IS was repeatedly superfused over the receptive fields for 5 min at 10 min intervals; substance P (SP 10(-6) and 10(-5) M) was applied during the last 5 min of the interval and during the subsequent IS stimulation. IS excited more than 80% of the mechano-heat sensitive (\"polymodal\") afferents with slowly conducting nerve fibres (n = 72), but none of the low-threshold mechanoreceptive slow and fast conducting units (n = 17). Slow conducting afferents with high mechanical threshold (n = 35) were weakly, and less frequently (< 20%), driven by IS. A majority, but not all, of the responsive units showed tachyphylaxis upon repeated IS application. None, however, lost its responsiveness completely. Conditioning heat stimulation (32-46.5 degrees C in 20 s) did not enhance the subsequent IS response, which may indicate that sensitizing substances normally released by a noxious heat stimulus were already contained in IS. No sensitization to mechanical (von Frey) or heat stimulation could be established in the period after the IS response had subsided and after the washout was completed, respectively. A short-lived sensitization may have been overlooked under these temporal restrictions. Conditioning SP in 10(-5) M but not in 10(-6) M concentration significantly increased the IS response of polymodal C fibres, by 58% on average (n = 14). SP did not excite the units. Comparing with previous data, we conclude that there is a significant synergism between inflammatory mediators, acting to induce more intense and more sustained discharge via many nociceptors than single mediators alone could achieve. Conditioning substance P can further enhance this algogenic action. Mechanisms of interaction and relative contributions of single substances remain to be elucidated."} {"id": "PMID:1282894", "title": "[Effect of suplatast tosilate (IPD-1151T) on types I-IV allergic reactions].", "content": "We examined the effect of suplatast tosilate (IPD-1151T), which exhibits a class-specific suppression of IgE antibody production, on types I-IV allergic reactions. 1) Type I reaction: IPD-1151T dose-dependently inhibited 48-hr homologous passive cutaneous anaphylaxis (PCA) when the agent was given p.o. 30 min prior to the antigen challenge. To observe the time course of the inhibitory activity, IPD-1151T in a dose of 50 mg/kg was given orally at various times prior to the antigen challenge. IPD-1151T showed inhibitory activity when it was given at 0.5 to 2 hr prior to the antigen challenge, and the maximum inhibition was found when the IPD-1151T pretreatment was 2-hr before the challenge. IPD-1151T also suppressed the antigen-induced degranulation of mesenteric mast cells and histamine release from peritoneal exudate cells of rats. 2) Type II reaction: Only a high dose of IPD-1151T given orally inhibited reversed cutaneous anaphylaxis in rats, whereas the agent did not affect Forssman shock in guinea pigs. 3) Types III and IV reactions: IPD-1151T neither affected the Arthus reaction in rabbits nor the picryl chloride-induced contact dermatitis and sheep erythrocytes-induced footpad reaction in mice. The results obtained here indicate that IPD-1151T shows a relatively specific suppression of the type I allergic reaction with the inhibition of degranulation and histamine release from mast cells.", "contents": "[Effect of suplatast tosilate (IPD-1151T) on types I-IV allergic reactions]. We examined the effect of suplatast tosilate (IPD-1151T), which exhibits a class-specific suppression of IgE antibody production, on types I-IV allergic reactions. 1) Type I reaction: IPD-1151T dose-dependently inhibited 48-hr homologous passive cutaneous anaphylaxis (PCA) when the agent was given p.o. 30 min prior to the antigen challenge. To observe the time course of the inhibitory activity, IPD-1151T in a dose of 50 mg/kg was given orally at various times prior to the antigen challenge. IPD-1151T showed inhibitory activity when it was given at 0.5 to 2 hr prior to the antigen challenge, and the maximum inhibition was found when the IPD-1151T pretreatment was 2-hr before the challenge. IPD-1151T also suppressed the antigen-induced degranulation of mesenteric mast cells and histamine release from peritoneal exudate cells of rats. 2) Type II reaction: Only a high dose of IPD-1151T given orally inhibited reversed cutaneous anaphylaxis in rats, whereas the agent did not affect Forssman shock in guinea pigs. 3) Types III and IV reactions: IPD-1151T neither affected the Arthus reaction in rabbits nor the picryl chloride-induced contact dermatitis and sheep erythrocytes-induced footpad reaction in mice. The results obtained here indicate that IPD-1151T shows a relatively specific suppression of the type I allergic reaction with the inhibition of degranulation and histamine release from mast cells."} {"id": "PMID:1282895", "title": "Toxic effects of oxygen-derived free radicals on rat pancreatic acini; an in vitro study.", "content": "Isolated pancreatic acini were incubated with either a combination of xanthine and xanthine oxidase which generates superoxide (O2), or hydrogen peroxide (H2O2), and the direct cytotoxic effect of active oxygen species on the pancreatic acini was examined in vitro in the isolated pancreatic acini system of the rat. Both amylase secretion and lactic dehydrogenase discharge were increased dose-dependently by the addition of xanthine and xanthine oxidase, and suppressed by the addition of a superoxide scavenger, superoxide dismutase. In addition, amylase and lectate dehydrogenase discharge was increased dose-dependently by hydrogen peroxide and decreased by catalase. These results suggest that superoxide and hydrogen peroxide directly injure pancreatic acinar cells and that active oxygen species are involved in the pathogenesis of acute pancreatitis.", "contents": "Toxic effects of oxygen-derived free radicals on rat pancreatic acini; an in vitro study. Isolated pancreatic acini were incubated with either a combination of xanthine and xanthine oxidase which generates superoxide (O2), or hydrogen peroxide (H2O2), and the direct cytotoxic effect of active oxygen species on the pancreatic acini was examined in vitro in the isolated pancreatic acini system of the rat. Both amylase secretion and lactic dehydrogenase discharge were increased dose-dependently by the addition of xanthine and xanthine oxidase, and suppressed by the addition of a superoxide scavenger, superoxide dismutase. In addition, amylase and lectate dehydrogenase discharge was increased dose-dependently by hydrogen peroxide and decreased by catalase. These results suggest that superoxide and hydrogen peroxide directly injure pancreatic acinar cells and that active oxygen species are involved in the pathogenesis of acute pancreatitis."} {"id": "PMID:1282896", "title": "Alpha-fetoprotein-producing cancer of the ampulla of Vater.", "content": "A case of cancer of the ampulla of Vater producing alpha-fetoprotein is reported and the literature is reviewed. As far as we know, the literature contains no reports of such a case. The preoperative serum alpha-fetoprotein was remarkably high (7,480 ng/ml), but it fell to normal values (under 5.0 ng/ml) after pancreatoduodenectomy, by means of which the lesion could be radically resected. In this case, the immunohistochemical findings at optical and electron microscopy clearly indicated the production of alpha-fetoprotein by the cancer cells of the ampulla of Vater.", "contents": "Alpha-fetoprotein-producing cancer of the ampulla of Vater. A case of cancer of the ampulla of Vater producing alpha-fetoprotein is reported and the literature is reviewed. As far as we know, the literature contains no reports of such a case. The preoperative serum alpha-fetoprotein was remarkably high (7,480 ng/ml), but it fell to normal values (under 5.0 ng/ml) after pancreatoduodenectomy, by means of which the lesion could be radically resected. In this case, the immunohistochemical findings at optical and electron microscopy clearly indicated the production of alpha-fetoprotein by the cancer cells of the ampulla of Vater."} {"id": "PMID:1282898", "title": "Non-radioactive detection of the most common mutations in the cystic fibrosis transmembrane conductance regulator gene by multiplex allele-specific polymerase chain reaction.", "content": "A rapid, simple, nonradioactive method for detection of four common mutations causing cystic fibrosis (CF) has been developed combining multiplexing with allele-specific polymerase chain reaction amplification. This approach (MASPCR) provides an easy assay for direct genotyping of normal and mutant CF alleles in homozygotes and heterozygotes. The strategy involves multiplex PCR of exons 10, 11, and 21 within the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a single reaction containing three common oligoprimers and either the four normal or four mutant oligos corresponding to the delta F508, G551D, G542X, and N1303K mutations. Primers are chosen so that the size of the four PCR products differ, thereby facilitating detection on agarose gels following amplification in the same reaction. Patient samples are primed with either four normal or four mutant oligo mixtures, and PCR products run in parallel on gels to detect band presence or absence. This approach provides a simple and potentially automated method for cost-effective population screening.", "contents": "Non-radioactive detection of the most common mutations in the cystic fibrosis transmembrane conductance regulator gene by multiplex allele-specific polymerase chain reaction. A rapid, simple, nonradioactive method for detection of four common mutations causing cystic fibrosis (CF) has been developed combining multiplexing with allele-specific polymerase chain reaction amplification. This approach (MASPCR) provides an easy assay for direct genotyping of normal and mutant CF alleles in homozygotes and heterozygotes. The strategy involves multiplex PCR of exons 10, 11, and 21 within the cystic fibrosis transmembrane conductance regulator (CFTR) gene in a single reaction containing three common oligoprimers and either the four normal or four mutant oligos corresponding to the delta F508, G551D, G542X, and N1303K mutations. Primers are chosen so that the size of the four PCR products differ, thereby facilitating detection on agarose gels following amplification in the same reaction. Patient samples are primed with either four normal or four mutant oligo mixtures, and PCR products run in parallel on gels to detect band presence or absence. This approach provides a simple and potentially automated method for cost-effective population screening."} {"id": "PMID:1282899", "title": "A germ line mutation within the coding sequence for the putative 5-phosphoribosyl-1-pyrophosphate binding site of hypoxanthine-guanine phosphoribosyltransferase (HPRT) in a Lesch-Nyhan patient: missense mutations within a functionally important region probably cause disease.", "content": "Lesch-Nyhan syndrome caused by a complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) is the result of a heterogeneous group of germ line mutations. Identification of each mutant gene provides valuable information as to the type of mutation that occurs spontaneously. We report here a newly identified HPRT mutation in a Japanese patient with Lesch-Nyhan syndrome. This gene, designated HPRT Tokyo, had a single nucleotide change from G to A, as identified by sequencing cDNA amplified by the polymerase chain reaction. Allele specific oligonucleotide hybridization analysis using amplified genomic DNA showed that the mutant gene was transmitted from the maternal germ line. This mutation would lead to an amino acid substitution of Asp for Gly at the amino acid position 140 located within the putative 5-phosphoribosyl-1-pyrophosphate (PRPP) binding region. Missense mutations in human HPRT deficient patients thus far reported tend to accumulate in this functionally active region. However, a comparison of the data suggested that both missense and synonymous mutations can occur at any coding sequence of the human germ line HPRT gene, but that a limited percentage of all the missense mutations cause disease. The probability that a mutation will cause disease tends to be higher when the missense mutation is within a functionally important sequence.", "contents": "A germ line mutation within the coding sequence for the putative 5-phosphoribosyl-1-pyrophosphate binding site of hypoxanthine-guanine phosphoribosyltransferase (HPRT) in a Lesch-Nyhan patient: missense mutations within a functionally important region probably cause disease. Lesch-Nyhan syndrome caused by a complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT) is the result of a heterogeneous group of germ line mutations. Identification of each mutant gene provides valuable information as to the type of mutation that occurs spontaneously. We report here a newly identified HPRT mutation in a Japanese patient with Lesch-Nyhan syndrome. This gene, designated HPRT Tokyo, had a single nucleotide change from G to A, as identified by sequencing cDNA amplified by the polymerase chain reaction. Allele specific oligonucleotide hybridization analysis using amplified genomic DNA showed that the mutant gene was transmitted from the maternal germ line. This mutation would lead to an amino acid substitution of Asp for Gly at the amino acid position 140 located within the putative 5-phosphoribosyl-1-pyrophosphate (PRPP) binding region. Missense mutations in human HPRT deficient patients thus far reported tend to accumulate in this functionally active region. However, a comparison of the data suggested that both missense and synonymous mutations can occur at any coding sequence of the human germ line HPRT gene, but that a limited percentage of all the missense mutations cause disease. The probability that a mutation will cause disease tends to be higher when the missense mutation is within a functionally important sequence."} {"id": "PMID:1282901", "title": "S-100 staining for the diagnosis of melanoma of the anal canal.", "content": "Thirty-two cases of anorectal melanoma are presented. These were diagnosed at the Pathology Department of the All India Institute of Medical Sciences, New Delhi, over a period of 18 years from 1970 to 1988. In 13 cases the clinical diagnosis was carcinoma melanoma was suspected clinically in only 9 of the 32 cases. Epithelioid tumours constituted the majority (26/32) 81%, followed by the pleomorphic type (4/32), 12.5% and then the sarcomatoid variant (2/32) 6.2%. Staining for S-100 protein was done on 21 cases and was found positive in 16/21 or 76%.", "contents": "S-100 staining for the diagnosis of melanoma of the anal canal. Thirty-two cases of anorectal melanoma are presented. These were diagnosed at the Pathology Department of the All India Institute of Medical Sciences, New Delhi, over a period of 18 years from 1970 to 1988. In 13 cases the clinical diagnosis was carcinoma melanoma was suspected clinically in only 9 of the 32 cases. Epithelioid tumours constituted the majority (26/32) 81%, followed by the pleomorphic type (4/32), 12.5% and then the sarcomatoid variant (2/32) 6.2%. Staining for S-100 protein was done on 21 cases and was found positive in 16/21 or 76%."} {"id": "PMID:1282903", "title": "Synthesis and biological activity of analogues of the C-terminal hexapeptide of substance P with modifications at glutaminyl and methioninyl residues. Structure-activity studies.", "content": "Analogues of [Orn6]-SP6-11 have been synthesized in which the methionyl residue is replaced by glutamine gamma-carboxamide substituted derivatives. These analogues where tested in three in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types. Substitution of the SCH3 group of the Met11 side chain by CONHCH3, CON(CH3)2, CONHPh and CONCH3Ph groups results in analogues which are full agonists in NK-1 and NK-2 preparations with the exception of the Glu[N(CH3)2]11 and the Glu(NHCH3)11 analogues, which are partial agonists at NK-1 and NK-2 receptors respectively. The Glu(NHCH3)11 analogue shows selectivity for the NK-1 receptor type and is equipotent to the Glu(NCH3Ph)11 analogue in the same receptor type. The latter analogue is 2.84 times more potent than the parent hexapeptide in the NK-2 preparation. The Glu(NHPh)11 analogue is a full agonist in the NK-3 preparation and equipotent to the parent hexapeptide, in contrast to the other analogues in which Met has been replaced by glutamine gamma-carboxamide substituted residues. It is concluded that for NK-1 receptor type the lipophilic character of Met11 side chain is not a determining factor for activity but it is an important factor for activity in the NK-2 receptor type and has a stronger effect when a phenyl group is present, thus leading to analogues which are full agonists and more potent than the parent hexapeptide.", "contents": "Synthesis and biological activity of analogues of the C-terminal hexapeptide of substance P with modifications at glutaminyl and methioninyl residues. Structure-activity studies. Analogues of [Orn6]-SP6-11 have been synthesized in which the methionyl residue is replaced by glutamine gamma-carboxamide substituted derivatives. These analogues where tested in three in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types. Substitution of the SCH3 group of the Met11 side chain by CONHCH3, CON(CH3)2, CONHPh and CONCH3Ph groups results in analogues which are full agonists in NK-1 and NK-2 preparations with the exception of the Glu[N(CH3)2]11 and the Glu(NHCH3)11 analogues, which are partial agonists at NK-1 and NK-2 receptors respectively. The Glu(NHCH3)11 analogue shows selectivity for the NK-1 receptor type and is equipotent to the Glu(NCH3Ph)11 analogue in the same receptor type. The latter analogue is 2.84 times more potent than the parent hexapeptide in the NK-2 preparation. The Glu(NHPh)11 analogue is a full agonist in the NK-3 preparation and equipotent to the parent hexapeptide, in contrast to the other analogues in which Met has been replaced by glutamine gamma-carboxamide substituted residues. It is concluded that for NK-1 receptor type the lipophilic character of Met11 side chain is not a determining factor for activity but it is an important factor for activity in the NK-2 receptor type and has a stronger effect when a phenyl group is present, thus leading to analogues which are full agonists and more potent than the parent hexapeptide."} {"id": "PMID:1282904", "title": "Extracellular Ca2+ sensing in C-cells and parathyroid cells.", "content": "An essential function of C-cells and parathyroid cells is to monitor the extracellular Ca2+ concentration. The Ca(2+)-dependent secretion of calcitonin (CT) and parathyroid hormone is known to be mediated by corresponding changes in the intracellular Ca2+ concentration. To address the question of whether Ca2+ influx through voltage-dependent Ca2+ channels couples the extracellular to the intracellular Ca2+, we applied the patch clamp technique to C-cells of the rMTC 44-2 cell line and to parathyroid cells of the PT-r cell line. The rMTC cells displayed dihydropyridine-sensitive, voltage-dependent, high-threshold Ca2+ channels which allowed ion influx even at the resting potential of about -40 mV. Increases of the concentration of the extracellular divalent cation or adding the Ca2+ channel agonist Bay K 8644 stimulated the steady state ion influx. In contrast, PT-r cells exhibited only fast inactivating, low-threshold Ca2+ channel currents with no steady state conductivity for Ca2+ at the resting potential of around -40 mV. We conclude that dihydropyridine-sensitive Ca2+ channels allow steady state transmembranous Ca2+ influx in C-cells, thereby increasing the cytosolic Ca2+ and CT secretion. Parathyroid cells, however, lack long-lasting Ca2+ channel currents and obviously sense the extracellular Ca2+ concentration by other mechanisms.", "contents": "Extracellular Ca2+ sensing in C-cells and parathyroid cells. An essential function of C-cells and parathyroid cells is to monitor the extracellular Ca2+ concentration. The Ca(2+)-dependent secretion of calcitonin (CT) and parathyroid hormone is known to be mediated by corresponding changes in the intracellular Ca2+ concentration. To address the question of whether Ca2+ influx through voltage-dependent Ca2+ channels couples the extracellular to the intracellular Ca2+, we applied the patch clamp technique to C-cells of the rMTC 44-2 cell line and to parathyroid cells of the PT-r cell line. The rMTC cells displayed dihydropyridine-sensitive, voltage-dependent, high-threshold Ca2+ channels which allowed ion influx even at the resting potential of about -40 mV. Increases of the concentration of the extracellular divalent cation or adding the Ca2+ channel agonist Bay K 8644 stimulated the steady state ion influx. In contrast, PT-r cells exhibited only fast inactivating, low-threshold Ca2+ channel currents with no steady state conductivity for Ca2+ at the resting potential of around -40 mV. We conclude that dihydropyridine-sensitive Ca2+ channels allow steady state transmembranous Ca2+ influx in C-cells, thereby increasing the cytosolic Ca2+ and CT secretion. Parathyroid cells, however, lack long-lasting Ca2+ channel currents and obviously sense the extracellular Ca2+ concentration by other mechanisms."} {"id": "PMID:1282905", "title": "Guidelines for creating effective slides and overhead transparencies used for teaching.", "content": "Slides, 35-mm transparencies, and overhead transparencies are popular teaching tools. This article outlines basic design principles and ways of producing transparencies so that the audience--whether student or professional--will benefit the most from this teaching device.", "contents": "Guidelines for creating effective slides and overhead transparencies used for teaching. Slides, 35-mm transparencies, and overhead transparencies are popular teaching tools. This article outlines basic design principles and ways of producing transparencies so that the audience--whether student or professional--will benefit the most from this teaching device."} {"id": "PMID:1282907", "title": "VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cell surface.", "content": "To elucidate the role of VLA-4 (alpha 4 beta 1 integrin) in tumor metastasis, we have transfected cDNA coding alpha 4 subunit into human fibrosarcoma (HT1080) cells. VLA-4-overexpressing HT-VC1 cells exhibited increased ability to interact with known ligands for VLA-4, such as CS1 peptide and VCAM-1 (vascular cell adhesion molecule-1). In addition, the in vitro invasive ability of HT-VC1 cells was augmented and the mRNA for type IV collagenase was increased in HT-VC1 cells. The induction of VCAM-1 molecules on lung endothelial cells of nude mice by tumor necrosis factor-alpha treatment resulted in augmentation of in vivo HT-VC1 cell adhesion to the lung endothelial cells. Thus, the VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cells, that is important for hematogenous metastasis.", "contents": "VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cell surface. To elucidate the role of VLA-4 (alpha 4 beta 1 integrin) in tumor metastasis, we have transfected cDNA coding alpha 4 subunit into human fibrosarcoma (HT1080) cells. VLA-4-overexpressing HT-VC1 cells exhibited increased ability to interact with known ligands for VLA-4, such as CS1 peptide and VCAM-1 (vascular cell adhesion molecule-1). In addition, the in vitro invasive ability of HT-VC1 cells was augmented and the mRNA for type IV collagenase was increased in HT-VC1 cells. The induction of VCAM-1 molecules on lung endothelial cells of nude mice by tumor necrosis factor-alpha treatment resulted in augmentation of in vivo HT-VC1 cell adhesion to the lung endothelial cells. Thus, the VLA-4 molecules on tumor cells initiate an adhesive interaction with VCAM-1 molecules on endothelial cells, that is important for hematogenous metastasis."} {"id": "PMID:1282908", "title": "Inhibition of cell attachment, invasion and metastasis of human carcinoma cells by anti-integrin beta 1 subunit antibody.", "content": "We investigated the expression of beta 1 integrins in human carcinoma cell lines, and the anti-metastatic and anti-invasive effects of a newly established anti-human beta 1 subunit monoclonal antibody designated NCC-INT-7. All the examined carcinoma cell lines expressed beta 1 integrins upon immunoblot analysis. NCC-INT-7 completely inhibited the adhesion of carcinoma cells to laminin, fibronectin, collagens and acetone-fixed tissues including lung, liver and brain. In an in vitro invasion model, NCC-INT-7 inhibited the invasion of human bladder carcinoma cell line T24 and human gastric carcinoma cell lines TMK-1, MKN-45 and MKN-74 through an artificially reconstructed basement membrane. In an in vivo nude mouse peritoneal dissemination model using MKN-45 and TMK-1, NCC-INT-7 significantly reduced the number of tumor nodules in the mesentery. In an in vivo nude mouse liver metastasis model using a serially transplantable human colonic carcinoma, COL-2-JCK, NCC-INT-7 significantly reduced the number of tumor nodules in liver. These results indicate that beta 1 integrins play an important role in the tissue attachment, migration, invasion and metastasis of human carcinoma cells, and that this new monoclonal antibody is useful for studies aimed at prevention of metastasis.", "contents": "Inhibition of cell attachment, invasion and metastasis of human carcinoma cells by anti-integrin beta 1 subunit antibody. We investigated the expression of beta 1 integrins in human carcinoma cell lines, and the anti-metastatic and anti-invasive effects of a newly established anti-human beta 1 subunit monoclonal antibody designated NCC-INT-7. All the examined carcinoma cell lines expressed beta 1 integrins upon immunoblot analysis. NCC-INT-7 completely inhibited the adhesion of carcinoma cells to laminin, fibronectin, collagens and acetone-fixed tissues including lung, liver and brain. In an in vitro invasion model, NCC-INT-7 inhibited the invasion of human bladder carcinoma cell line T24 and human gastric carcinoma cell lines TMK-1, MKN-45 and MKN-74 through an artificially reconstructed basement membrane. In an in vivo nude mouse peritoneal dissemination model using MKN-45 and TMK-1, NCC-INT-7 significantly reduced the number of tumor nodules in the mesentery. In an in vivo nude mouse liver metastasis model using a serially transplantable human colonic carcinoma, COL-2-JCK, NCC-INT-7 significantly reduced the number of tumor nodules in liver. These results indicate that beta 1 integrins play an important role in the tissue attachment, migration, invasion and metastasis of human carcinoma cells, and that this new monoclonal antibody is useful for studies aimed at prevention of metastasis."} {"id": "PMID:1282909", "title": "Glomeruloid structures as vascular reaction in human gastrointestinal carcinoma.", "content": "Malignant tumors induce angiogenesis and modulation of microvasculature. Based on histologic and immunohistochemical analysis of human surgical material, we describe here the occurrence of glomeruloid structures in gastrointestinal carcinomas, and compare them with the microvasculature in inflammatory granulation tissue. The glomeruloid structures were composed of clusters of mutually fused capillaries with prominent swelling of endothelial cells and pericytes. They were thought to be specific for glioblastoma of the brain. The glomeruloid structures were observed juxtaposed to carcinoma nests in one-third of gastric carcinoma of intestinal type and colorectal carcinoma in the area of invasive growth beyond the muscularis mucosae. They were not observed in gastric carcinoma of diffuse type, intramucosal carcinoma, or inflammatory granulation tissue. The glomeruloid structures can be regarded as an extreme example of endothelial hyperplastic changes observed in cancer stroma. Our results suggested that glomeruloid structures can occur in carcinomas as vascular reaction, a mechanism different from that in inflammatory granulation tissues.", "contents": "Glomeruloid structures as vascular reaction in human gastrointestinal carcinoma. Malignant tumors induce angiogenesis and modulation of microvasculature. Based on histologic and immunohistochemical analysis of human surgical material, we describe here the occurrence of glomeruloid structures in gastrointestinal carcinomas, and compare them with the microvasculature in inflammatory granulation tissue. The glomeruloid structures were composed of clusters of mutually fused capillaries with prominent swelling of endothelial cells and pericytes. They were thought to be specific for glioblastoma of the brain. The glomeruloid structures were observed juxtaposed to carcinoma nests in one-third of gastric carcinoma of intestinal type and colorectal carcinoma in the area of invasive growth beyond the muscularis mucosae. They were not observed in gastric carcinoma of diffuse type, intramucosal carcinoma, or inflammatory granulation tissue. The glomeruloid structures can be regarded as an extreme example of endothelial hyperplastic changes observed in cancer stroma. Our results suggested that glomeruloid structures can occur in carcinomas as vascular reaction, a mechanism different from that in inflammatory granulation tissues."} {"id": "PMID:1282910", "title": "Effect of recombinant human D-factor on the growth of leukemic blast progenitors from acute myeloblastic leukemia patients.", "content": "We studied the effects of D-factor on the growth of leukemic blast progenitors from 15 patients with acute myeloblastic leukemia and two leukemia cell lines in methylcellulose and suspension cultures. When stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor or interleukin-3, leukemic blast progenitors undergo terminal division with limited differentiation in methylcellulose culture, forming blast colonies. Leukemic blast progenitors can renew themselves. The self-renewal can be detected as secondary colony formation after replating primary blast colonies in fresh methylcellulose media and by the growth of clonogenic cells in suspension culture. D-Factor suppressed primary and secondary colony formation in methylcellulose culture. Furthermore, D-factor suppressed clonogenic cell recovery in suspension culture. The suppression by D-factor of the growth of leukemic blast progenitors was not significantly dependent upon the colony-stimulating factors used as growth-stimulating factors. High concentration of G-CSF did not overcome the suppressive effect of D-factor. The results indicate that D-factor is effective in suppressing not only terminal division but also self-renewal of leukemic blast progenitors.", "contents": "Effect of recombinant human D-factor on the growth of leukemic blast progenitors from acute myeloblastic leukemia patients. We studied the effects of D-factor on the growth of leukemic blast progenitors from 15 patients with acute myeloblastic leukemia and two leukemia cell lines in methylcellulose and suspension cultures. When stimulated by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor or interleukin-3, leukemic blast progenitors undergo terminal division with limited differentiation in methylcellulose culture, forming blast colonies. Leukemic blast progenitors can renew themselves. The self-renewal can be detected as secondary colony formation after replating primary blast colonies in fresh methylcellulose media and by the growth of clonogenic cells in suspension culture. D-Factor suppressed primary and secondary colony formation in methylcellulose culture. Furthermore, D-factor suppressed clonogenic cell recovery in suspension culture. The suppression by D-factor of the growth of leukemic blast progenitors was not significantly dependent upon the colony-stimulating factors used as growth-stimulating factors. High concentration of G-CSF did not overcome the suppressive effect of D-factor. The results indicate that D-factor is effective in suppressing not only terminal division but also self-renewal of leukemic blast progenitors."} {"id": "PMID:1282911", "title": "Establishment of an enzyme immunoassay using monoclonal antibody (HG1-219) and its application for the diagnosis of hepatocellular carcinoma.", "content": "A monoclonal antibody (MoAb HG1-219) against a human gastric cancer cell line (HuG-1) and its shedding antigen (HG1-219 Ag) was generated and a solid-phase sandwich enzyme immunoassay (EIA-219) was developed. The mean serum HG1-219 Ag concentration in normal individuals was 30.5 +/- 14.5 U/ml measured by EIA-219. When the mean +3 SD of the antigen concentration in normal individuals was used as a cut-off level, 4.3% (2/47) of patients with chronic hepatitis, 9.1% (4/44) of cirrhotic patients and 37.5% (18/48) of patients with hepatocellular carcinoma (HCC) had HG1-219 Ag above the cut-off value. The positive rates of a-fetoprotein (AFP) (> 400 ng/ml) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC were 26.7% (12/45) and 33.3% (12/36), respectively. There was no significant correlation between HG1-219 Ag and AFP or PIVKA-II in patients with HCC. The combination assay of EIA-219, AFP and PIVKA-II for HCC gave the positive rate of 75% (27/36). The effect of periodic acid on the HG1-219 Ag and the inhibition of EIA-219 by CA 19-9 suggest that the epitope of HG1-219 Ag is a suger chain similar to CA 19-9.", "contents": "Establishment of an enzyme immunoassay using monoclonal antibody (HG1-219) and its application for the diagnosis of hepatocellular carcinoma. A monoclonal antibody (MoAb HG1-219) against a human gastric cancer cell line (HuG-1) and its shedding antigen (HG1-219 Ag) was generated and a solid-phase sandwich enzyme immunoassay (EIA-219) was developed. The mean serum HG1-219 Ag concentration in normal individuals was 30.5 +/- 14.5 U/ml measured by EIA-219. When the mean +3 SD of the antigen concentration in normal individuals was used as a cut-off level, 4.3% (2/47) of patients with chronic hepatitis, 9.1% (4/44) of cirrhotic patients and 37.5% (18/48) of patients with hepatocellular carcinoma (HCC) had HG1-219 Ag above the cut-off value. The positive rates of a-fetoprotein (AFP) (> 400 ng/ml) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) for HCC were 26.7% (12/45) and 33.3% (12/36), respectively. There was no significant correlation between HG1-219 Ag and AFP or PIVKA-II in patients with HCC. The combination assay of EIA-219, AFP and PIVKA-II for HCC gave the positive rate of 75% (27/36). The effect of periodic acid on the HG1-219 Ag and the inhibition of EIA-219 by CA 19-9 suggest that the epitope of HG1-219 Ag is a suger chain similar to CA 19-9."} {"id": "PMID:1282913", "title": "Characterization of normal breast epithelial cells in primary cultures: differentiation and growth factor receptors studies.", "content": "The growth and differentiation of normal human mammary epithelial cells (HMEC) were studied after propagation of serial cultures from breast tissue biopsies from 42 mammoplasty patients. Cells were grown for up to 7 mo. in low calcium medium. HMEC cultures displayed heterogeneous growth patterns, according to the average doubling time of 44 +/- 6 h for 32 generations. Proliferation peaked at Day 30. HMEC maintained a normal karyotype and were organized in ductlike structures when cultured in collagen gel matrix. The cultures retained several phenotype traits of the epithelial lineage, including the expression of cytokeratins 18 and 19, specific mammary gland antigens, as shown by indirect HMEC immunostaining by the monoclonal antibodies DF3, EMA, 7B10, and 1BE12. Estrogen receptors were undetectable, whereas progesterone receptors were present at very low density. High-affinity cell surface receptors for epidermal growth factor (EGF) (Kd = 1.1 x 10(-10) M) were observed at a density of 50,000 to 100,000 sites per cell. Accordingly, [3H]thymidine incorporation in HMEC was optimally stimulated by EGF at concentrations of 10(-11) to 10(-10) M. HMEC were also seen to possess functional VIP receptors linked to the adenylate cyclase system, as we previously observed in seven human breast cancer cell lines. These results show that long-term cultures of HMEC provide useful models for studying the growth and differentiation of the normal human mammary gland, and the role of growth factors and hormones in these functions.", "contents": "Characterization of normal breast epithelial cells in primary cultures: differentiation and growth factor receptors studies. The growth and differentiation of normal human mammary epithelial cells (HMEC) were studied after propagation of serial cultures from breast tissue biopsies from 42 mammoplasty patients. Cells were grown for up to 7 mo. in low calcium medium. HMEC cultures displayed heterogeneous growth patterns, according to the average doubling time of 44 +/- 6 h for 32 generations. Proliferation peaked at Day 30. HMEC maintained a normal karyotype and were organized in ductlike structures when cultured in collagen gel matrix. The cultures retained several phenotype traits of the epithelial lineage, including the expression of cytokeratins 18 and 19, specific mammary gland antigens, as shown by indirect HMEC immunostaining by the monoclonal antibodies DF3, EMA, 7B10, and 1BE12. Estrogen receptors were undetectable, whereas progesterone receptors were present at very low density. High-affinity cell surface receptors for epidermal growth factor (EGF) (Kd = 1.1 x 10(-10) M) were observed at a density of 50,000 to 100,000 sites per cell. Accordingly, [3H]thymidine incorporation in HMEC was optimally stimulated by EGF at concentrations of 10(-11) to 10(-10) M. HMEC were also seen to possess functional VIP receptors linked to the adenylate cyclase system, as we previously observed in seven human breast cancer cell lines. These results show that long-term cultures of HMEC provide useful models for studying the growth and differentiation of the normal human mammary gland, and the role of growth factors and hormones in these functions."} {"id": "PMID:1282916", "title": "Role of QT interval at onset of acute myocardial infarction in predicting early phase ventricular arrhythmia.", "content": "In this study, the QTc interval was determined in 51 patients of acute myocardial infarction and the incidence of ventricular arrhythmias in them was noted. It was found that the QTc interval was prolonged (more than 0.44 sec) in all the 33 patients who developed ventricular arrhythmias, while it was below 0.44 sec in all the 18 patients who did not develop ventricular arrhythmia.", "contents": "Role of QT interval at onset of acute myocardial infarction in predicting early phase ventricular arrhythmia. In this study, the QTc interval was determined in 51 patients of acute myocardial infarction and the incidence of ventricular arrhythmias in them was noted. It was found that the QTc interval was prolonged (more than 0.44 sec) in all the 33 patients who developed ventricular arrhythmias, while it was below 0.44 sec in all the 18 patients who did not develop ventricular arrhythmia."} {"id": "PMID:1282914", "title": "A transformed human epithelial cell line that retains tight junctions post crisis.", "content": "The successful establishment of a postcrisis SV-40 T antigen transformed epithelial cell line, 1HAEo-, which retains tight junctions and vectorial ion transport, is described. Immunocytochemical analysis of 1HAEo- cells shows a defined pattern of cytokeratin staining and a characteristic pericellular localization of the adhesion molecule cellCAM 120/80, indicating the presence of junctional complexes. The presence of both tight junctions and desmosomes has been confirmed by electron microscopy. Cell monolayers have good transepithelial resistance measured in Ussing chambers. Cells increase chloride ion transport in response to addition of agents that raise either intracellular cAMP or calcium, measured either by 36Cl- efflux or whole-cell patch clamp. An increase in short-circuit current, in response to these agents, can be measured in Ussing chambers. The presence of a depolarization-induced outwardly rectifying 45 pS chloride channel has been demonstrated in single cell detached membrane patches. In addition, the cells have been found to express mucin mRNA. These cells therefore demonstrate that it is possible to select transformed cell clones with particular morphologic characteristics, i.e. the presence of tight junctions and cell polarity, which also retain useful epithelial cell-specific functions, including vectorial ion transport. They also provide a major resource for the study of the structure and function of human epithelia.", "contents": "A transformed human epithelial cell line that retains tight junctions post crisis. The successful establishment of a postcrisis SV-40 T antigen transformed epithelial cell line, 1HAEo-, which retains tight junctions and vectorial ion transport, is described. Immunocytochemical analysis of 1HAEo- cells shows a defined pattern of cytokeratin staining and a characteristic pericellular localization of the adhesion molecule cellCAM 120/80, indicating the presence of junctional complexes. The presence of both tight junctions and desmosomes has been confirmed by electron microscopy. Cell monolayers have good transepithelial resistance measured in Ussing chambers. Cells increase chloride ion transport in response to addition of agents that raise either intracellular cAMP or calcium, measured either by 36Cl- efflux or whole-cell patch clamp. An increase in short-circuit current, in response to these agents, can be measured in Ussing chambers. The presence of a depolarization-induced outwardly rectifying 45 pS chloride channel has been demonstrated in single cell detached membrane patches. In addition, the cells have been found to express mucin mRNA. These cells therefore demonstrate that it is possible to select transformed cell clones with particular morphologic characteristics, i.e. the presence of tight junctions and cell polarity, which also retain useful epithelial cell-specific functions, including vectorial ion transport. They also provide a major resource for the study of the structure and function of human epithelia."} {"id": "PMID:1282915", "title": "Cyclic AMP-dependent protein kinase in human embryonic palate mesenchymal cells.", "content": "Growth and differentiation of cells derived from the embryonic palate are critically dependent on the intracellular cAMP-mediated signal transduction pathway. Human embryonic palate mesenchymal (HEPM) cells have been widely used to examine the effect of teratogens on palatal tissue growth and differentiation, as well as a prescreen for environmental teratogens. This study examined responsiveness of HEPM cells to agents known to stimulate adenylate cyclase, characterized cAMP-dependent protein kinases (cAMP-dPK) (EC 2.7.1.37) and investigated to what extent HEPM cells reveal adaptational responses to cAMP at the level of cAMP-dependent protein kinase. HEPM cells exhibited a total cell cycle transit time of approximately 22 h and responded maximally, when confluent, to prostacyclin (PGI2), prostaglandin E2 (PGE2), and isoproterenol with time- and dose-dependent increases in intracellular levels of cAMP. The order of sensitivity to hormonal activation of adenylate cyclase was PGE2 > isoproterenol > PGI2. Basal cAMP-dependent protein kinases activity was 0.184 fmol phosphate transferred from ATP to histone per microgram protein per minute under conditions where endogenous phosphatases did not significantly affect protein phosphorylation. Regulatory subunits of cAMP-dPK in HEPM cells were characterized by the binding of [3H]cAMP to cytosolic fractions. Specific binding was saturable at approximately 50 nM indicating the presence of binding sites that are finite in number. Calculation of half-maximal binding yielded an estimated Kd of 25 nM indicating the presence of high affinity binding sites. Cyclic AMP-dPK regulatory subunits were also photoaffinity labeled with 8-N3-[32P]-cAMP, subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and radiolabeled bands visualized by autoradiography. Photoactivated incorporation of 8-N3-[32P]cAMP was detected into two proteins of molecular weight (M(r)) 45,000 and M(r) 51,000 representing, respectively, the RI alpha and RII beta subunits of cAMP-dPK. Binding of [32P]8-azido cAMP to proteins of M(r) 45,000 (RI alpha) and M(r) 51,000 (RII beta) was increased in response to elevation of intracellular cAMP via inhibition of its breakdown with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, or by direct activation of adenylate cyclase with forskolin. HEPM cells thus revealed adaptational responses to cAMP at the level of cAMP-dependent protein kinase. Characterization of the cAMP signal transduction pathway in HEPM cells, derived from embryonic palatal tissue which is critically dependent on this pathway for normal development, may provide information fundamental to a clear understanding of cellular events involved in palatal ontogeny. These results highlight several important differences between HEPM cells and murine embryonic palate mesenchymal cells.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Cyclic AMP-dependent protein kinase in human embryonic palate mesenchymal cells. Growth and differentiation of cells derived from the embryonic palate are critically dependent on the intracellular cAMP-mediated signal transduction pathway. Human embryonic palate mesenchymal (HEPM) cells have been widely used to examine the effect of teratogens on palatal tissue growth and differentiation, as well as a prescreen for environmental teratogens. This study examined responsiveness of HEPM cells to agents known to stimulate adenylate cyclase, characterized cAMP-dependent protein kinases (cAMP-dPK) (EC 2.7.1.37) and investigated to what extent HEPM cells reveal adaptational responses to cAMP at the level of cAMP-dependent protein kinase. HEPM cells exhibited a total cell cycle transit time of approximately 22 h and responded maximally, when confluent, to prostacyclin (PGI2), prostaglandin E2 (PGE2), and isoproterenol with time- and dose-dependent increases in intracellular levels of cAMP. The order of sensitivity to hormonal activation of adenylate cyclase was PGE2 > isoproterenol > PGI2. Basal cAMP-dependent protein kinases activity was 0.184 fmol phosphate transferred from ATP to histone per microgram protein per minute under conditions where endogenous phosphatases did not significantly affect protein phosphorylation. Regulatory subunits of cAMP-dPK in HEPM cells were characterized by the binding of [3H]cAMP to cytosolic fractions. Specific binding was saturable at approximately 50 nM indicating the presence of binding sites that are finite in number. Calculation of half-maximal binding yielded an estimated Kd of 25 nM indicating the presence of high affinity binding sites. Cyclic AMP-dPK regulatory subunits were also photoaffinity labeled with 8-N3-[32P]-cAMP, subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and radiolabeled bands visualized by autoradiography. Photoactivated incorporation of 8-N3-[32P]cAMP was detected into two proteins of molecular weight (M(r)) 45,000 and M(r) 51,000 representing, respectively, the RI alpha and RII beta subunits of cAMP-dPK. Binding of [32P]8-azido cAMP to proteins of M(r) 45,000 (RI alpha) and M(r) 51,000 (RII beta) was increased in response to elevation of intracellular cAMP via inhibition of its breakdown with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, or by direct activation of adenylate cyclase with forskolin. HEPM cells thus revealed adaptational responses to cAMP at the level of cAMP-dependent protein kinase. Characterization of the cAMP signal transduction pathway in HEPM cells, derived from embryonic palatal tissue which is critically dependent on this pathway for normal development, may provide information fundamental to a clear understanding of cellular events involved in palatal ontogeny. These results highlight several important differences between HEPM cells and murine embryonic palate mesenchymal cells.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282918", "title": "A study of aluminium phosphide poisoning with special reference to its spot diagnosis by silver nitrate test.", "content": "A total of 45 cases of Aluminium phosphide poisoning were studied from December 1989 to November 1990. Silver nitrate (AgNO3) test was positive in gastric aspirate in all cases (100%) who took fresh tablets and negative in those who took exposed tablets. The test was also positive in breath but had a lower sensitivity. Majority of patients revealed ECG abnormalities.", "contents": "A study of aluminium phosphide poisoning with special reference to its spot diagnosis by silver nitrate test. A total of 45 cases of Aluminium phosphide poisoning were studied from December 1989 to November 1990. Silver nitrate (AgNO3) test was positive in gastric aspirate in all cases (100%) who took fresh tablets and negative in those who took exposed tablets. The test was also positive in breath but had a lower sensitivity. Majority of patients revealed ECG abnormalities."} {"id": "PMID:1282919", "title": "Cholinergic innervation of the human thalamus: dual origin and differential nuclear distribution.", "content": "The cholinergic innervation of the human thalamus was studied with antibodies against the enzyme choline acetyltransferase (ChAT) and nerve growth factor receptor (NGFr). Acetylcholinesterase histochemistry was used to delineate nuclear boundaries. All thalamic nuclei displayed ChAT-positive axons and varicosities. Only the medial habenula contained ChAT-positive perikarya. Some intralaminar nuclei (central medial, central lateral, and paracentral), the reticular nucleus, midline nuclei (paraventricular and reuniens), some nuclei associated with the limbic system (anterodorsal nucleus and medially situated patches in the mediodorsal nucleus) and the lateral geniculate nucleus displayed the highest density of ChAT-positive axonal varicosities. The remaining sensory relay nuclei and the nuclei interconnected with the motor and association cortex displayed a lower level of innervation. Immunoreactivity for NGFr was observed in cholinergic neurons of the basal forebrain but not in cholinergic neurons of the upper brainstem. The contribution of basal forebrain afferents to the cholinergic innervation of the human thalamus was therefore studied with the aid of NGFr-immunoreactive axonal staining. The anterior intralaminar nuclei, the reticular nucleus, and medially situated patches in the mediodorsal nucleus displayed a substantial number of NGFr-positive varicose axons, presumably originating in the basal forebrain. Rare NGFr-positive axonal profiles were also seen in many of the other thalamic nuclei. These observations suggest that thalamic nuclei affiliated with limbic structures and with the ascending reticular activating system are likely to be under particularly intense cholinergic influence. While the vast majority of thalamic cholinergic input seems to come from the upper brainstem, the intralaminar and reticular nuclei, and especially medially situated patches within the mediodorsal nucleus also appear to receive substantial cholinergic innervation from the basal forebrain.", "contents": "Cholinergic innervation of the human thalamus: dual origin and differential nuclear distribution. The cholinergic innervation of the human thalamus was studied with antibodies against the enzyme choline acetyltransferase (ChAT) and nerve growth factor receptor (NGFr). Acetylcholinesterase histochemistry was used to delineate nuclear boundaries. All thalamic nuclei displayed ChAT-positive axons and varicosities. Only the medial habenula contained ChAT-positive perikarya. Some intralaminar nuclei (central medial, central lateral, and paracentral), the reticular nucleus, midline nuclei (paraventricular and reuniens), some nuclei associated with the limbic system (anterodorsal nucleus and medially situated patches in the mediodorsal nucleus) and the lateral geniculate nucleus displayed the highest density of ChAT-positive axonal varicosities. The remaining sensory relay nuclei and the nuclei interconnected with the motor and association cortex displayed a lower level of innervation. Immunoreactivity for NGFr was observed in cholinergic neurons of the basal forebrain but not in cholinergic neurons of the upper brainstem. The contribution of basal forebrain afferents to the cholinergic innervation of the human thalamus was therefore studied with the aid of NGFr-immunoreactive axonal staining. The anterior intralaminar nuclei, the reticular nucleus, and medially situated patches in the mediodorsal nucleus displayed a substantial number of NGFr-positive varicose axons, presumably originating in the basal forebrain. Rare NGFr-positive axonal profiles were also seen in many of the other thalamic nuclei. These observations suggest that thalamic nuclei affiliated with limbic structures and with the ascending reticular activating system are likely to be under particularly intense cholinergic influence. While the vast majority of thalamic cholinergic input seems to come from the upper brainstem, the intralaminar and reticular nuclei, and especially medially situated patches within the mediodorsal nucleus also appear to receive substantial cholinergic innervation from the basal forebrain."} {"id": "PMID:1282920", "title": "Differential expression of GABAA/benzodiazepine receptor beta 1, beta 2, and beta 3 subunit mRNAs in the developing mouse cerebellum.", "content": "Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian cerebellum. Cerebellar granule, Purkinje, and deep nuclear neurons are known to receive GABAergic afferents. Since GABA exerts its inhibitory effects via GABA receptors, it is of interest to determine the temporal relationship between the formation of GABAergic synapses and the expression of genes coding for the GABA receptor. In a previous study, we have examined the developmental expression of binding sites for [3H]muscimol, which binds with high affinity to the beta subunits of the GABAA/benzodiazepine (GABAA/BZ) receptor. In the present study, [35S]cRNA probes were used to examine the appearance and distribution of GABAA/BZ beta 1, beta 2, and beta 3 subunit mRNAs in the developing C57BL/6 mouse cerebellum by in situ hybridization. In the adult cerebellum, the distribution of the three subunit mRNAs was clearly different, despite considerable overlap, and their temporal expression differed throughout postnatal development. The beta 1 hybridization signal appeared within the cerebellar cortex during the second postnatal week as a discrete band at the interface of the molecular and granule cell layers. Grains were distributed diffusely over small densely staining cells surrounding the Purkinje cells; relatively few grains were visible over Purkinje cell bodies themselves. This distribution may reflect an association with Bergmann glia or basket cells. The beta 2 and beta 3 hybridization signals were present considerably earlier than that of the beta 1 mRNA. The beta 2 signal was present at birth in the molecular/Purkinje cell layer; as development progressed, the signal became increasingly intense over both granule and Purkinje cells. At birth, the beta 3 subunit mRNA was present in the external germinal and molecular layers, later becoming largely localized within the granule cell layer. Dense beta 2 and beta 3 cRNA probe labeling was present over the adult granule cell layer. Moderate levels of beta 2 signal were seen over Purkinje cell bodies; considerably less labeling was observed with the beta 3 probe. The adult distribution of beta 2 and beta 3 cRNA probes showed good spatial correspondence with the known GABAA receptor beta subunit markers, [3H]-muscimol and the mAb 62-3G1 antibody, each being present within the granule cell layer. Our results indicate that the temporal expression of GABAA/BZ receptor beta subunit messages within a given cell type may be independently regulated, and that acquisition of the beta 2 and beta 3 mRNAs occurs before these cells become integrated into mature synaptic circuits.", "contents": "Differential expression of GABAA/benzodiazepine receptor beta 1, beta 2, and beta 3 subunit mRNAs in the developing mouse cerebellum. Gamma aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian cerebellum. Cerebellar granule, Purkinje, and deep nuclear neurons are known to receive GABAergic afferents. Since GABA exerts its inhibitory effects via GABA receptors, it is of interest to determine the temporal relationship between the formation of GABAergic synapses and the expression of genes coding for the GABA receptor. In a previous study, we have examined the developmental expression of binding sites for [3H]muscimol, which binds with high affinity to the beta subunits of the GABAA/benzodiazepine (GABAA/BZ) receptor. In the present study, [35S]cRNA probes were used to examine the appearance and distribution of GABAA/BZ beta 1, beta 2, and beta 3 subunit mRNAs in the developing C57BL/6 mouse cerebellum by in situ hybridization. In the adult cerebellum, the distribution of the three subunit mRNAs was clearly different, despite considerable overlap, and their temporal expression differed throughout postnatal development. The beta 1 hybridization signal appeared within the cerebellar cortex during the second postnatal week as a discrete band at the interface of the molecular and granule cell layers. Grains were distributed diffusely over small densely staining cells surrounding the Purkinje cells; relatively few grains were visible over Purkinje cell bodies themselves. This distribution may reflect an association with Bergmann glia or basket cells. The beta 2 and beta 3 hybridization signals were present considerably earlier than that of the beta 1 mRNA. The beta 2 signal was present at birth in the molecular/Purkinje cell layer; as development progressed, the signal became increasingly intense over both granule and Purkinje cells. At birth, the beta 3 subunit mRNA was present in the external germinal and molecular layers, later becoming largely localized within the granule cell layer. Dense beta 2 and beta 3 cRNA probe labeling was present over the adult granule cell layer. Moderate levels of beta 2 signal were seen over Purkinje cell bodies; considerably less labeling was observed with the beta 3 probe. The adult distribution of beta 2 and beta 3 cRNA probes showed good spatial correspondence with the known GABAA receptor beta subunit markers, [3H]-muscimol and the mAb 62-3G1 antibody, each being present within the granule cell layer. Our results indicate that the temporal expression of GABAA/BZ receptor beta subunit messages within a given cell type may be independently regulated, and that acquisition of the beta 2 and beta 3 mRNAs occurs before these cells become integrated into mature synaptic circuits."} {"id": "PMID:1282921", "title": "Direct and indirect \"cortico\"-rubral and rubro-cerebellar cortical projections in the pigeon.", "content": "In birds the red nucleus is the most rostral cell group in the brain having projections to all levels of the spinal cord (Cabot et al., Prog. Brain Res., 57:79-108, 1982), but its sources of afferents are incompletely known. In order to determine these, a series retrograde and anterograde tracing experiments was carried out, largely with cholera toxin B-chain conjugated to horseradish peroxidase. The results show that a sparse and diffuse projection to the red nucleus arises from deep regions of the hyperstriatum accessorium (HA) of the anterior Wulst, and that a much more dense projection arises from the caudal part of the nucleus principalis precommissuralis and the medial part of the medial spiriform nucleus (SpMm). These last two sources were themselves shown to receive a substantial projection from HA of the anterior Wulst. The red nucleus was also shown to project upon the cerebellar cortex of lobule VI, and SpM upon the cerebellar cortex of lobules VI through IX (Karten and Finger, Brain Res., 102:335-338, 1976; Clarke, J. Comp. Neurol., 174:535-552, 1977). Double retrograde labelling experiments with fluorescein and rhodamine labelled latex microspheres injected into the cerebellar cortex and spinal cord showed that the rubrocerebellar cortical neurons are a different population from, although intermixed with, the rubrospinal neurons.", "contents": "Direct and indirect \"cortico\"-rubral and rubro-cerebellar cortical projections in the pigeon. In birds the red nucleus is the most rostral cell group in the brain having projections to all levels of the spinal cord (Cabot et al., Prog. Brain Res., 57:79-108, 1982), but its sources of afferents are incompletely known. In order to determine these, a series retrograde and anterograde tracing experiments was carried out, largely with cholera toxin B-chain conjugated to horseradish peroxidase. The results show that a sparse and diffuse projection to the red nucleus arises from deep regions of the hyperstriatum accessorium (HA) of the anterior Wulst, and that a much more dense projection arises from the caudal part of the nucleus principalis precommissuralis and the medial part of the medial spiriform nucleus (SpMm). These last two sources were themselves shown to receive a substantial projection from HA of the anterior Wulst. The red nucleus was also shown to project upon the cerebellar cortex of lobule VI, and SpM upon the cerebellar cortex of lobules VI through IX (Karten and Finger, Brain Res., 102:335-338, 1976; Clarke, J. Comp. Neurol., 174:535-552, 1977). Double retrograde labelling experiments with fluorescein and rhodamine labelled latex microspheres injected into the cerebellar cortex and spinal cord showed that the rubrocerebellar cortical neurons are a different population from, although intermixed with, the rubrospinal neurons."} {"id": "PMID:1282922", "title": "[Cancer of the testis after Hodgkin's disease. Apropos of 2 cases].", "content": "We report about two cases of cancer of the testis occurring 2 and 7 years after Hodgkin's disease treated with combined chemotherapy and radiation therapy. From an etiopathogenic point of view, this association may, of course, be accidental, but it may also have an iatrogenic origin or be caused by contiguous carcinogenesis, or even by an immune deficiency. In addition to orchidectomy, the therapeutic history of these patients requires an adaptation of the treatment of their tumors of the testes.", "contents": "[Cancer of the testis after Hodgkin's disease. Apropos of 2 cases]. We report about two cases of cancer of the testis occurring 2 and 7 years after Hodgkin's disease treated with combined chemotherapy and radiation therapy. From an etiopathogenic point of view, this association may, of course, be accidental, but it may also have an iatrogenic origin or be caused by contiguous carcinogenesis, or even by an immune deficiency. In addition to orchidectomy, the therapeutic history of these patients requires an adaptation of the treatment of their tumors of the testes."} {"id": "PMID:1282923", "title": "Immunohistochemical detection of desmosomes in oral squamous cell carcinomas: correlation with differentiation, mode of invasion, and metastatic potential.", "content": "An expression of desmosomal glycoprotein 1 (DG 1) was immunohistochemically examined in 77 biopsies and 21 metastatic cervical lymph nodes of oral squamous cell carcinomas (SCC). In the primary tumors the DG 1 expression was significantly reduced at the invasive site of poorly differentiated and highly invasive tumors. In cases of metastases in cervical lymph nodes, the DG 1 staining at the invasive site of the primary tumor was significantly less than that of nonmetastatic cases. The DG 1 expression in the metastatic lymph nodes was as weak as that in the primary tumor. Thus, we suggest that immunohistochemical investigation of DG 1 expression in oral SCC is valuable in predicting tumor behavior.", "contents": "Immunohistochemical detection of desmosomes in oral squamous cell carcinomas: correlation with differentiation, mode of invasion, and metastatic potential. An expression of desmosomal glycoprotein 1 (DG 1) was immunohistochemically examined in 77 biopsies and 21 metastatic cervical lymph nodes of oral squamous cell carcinomas (SCC). In the primary tumors the DG 1 expression was significantly reduced at the invasive site of poorly differentiated and highly invasive tumors. In cases of metastases in cervical lymph nodes, the DG 1 staining at the invasive site of the primary tumor was significantly less than that of nonmetastatic cases. The DG 1 expression in the metastatic lymph nodes was as weak as that in the primary tumor. Thus, we suggest that immunohistochemical investigation of DG 1 expression in oral SCC is valuable in predicting tumor behavior."} {"id": "PMID:1282924", "title": "Measurement of proliferating cell nuclear antigen (PCNA) and its clinical application in oral cancers.", "content": "The PCNA score was measured in oral squamous cell carcinoma (SCC), and its relationship to other cell proliferation markers, Ki-67 score, S-phase fraction (SPF), and AgNORs counts was investigated. The PCNA score ranged from 0.4% to 43.5% with an average value of 22.8%, the Ki-67 score ranged from 4.9% to 40% with an average of 24.1%, and the SPF ranged from 0.4% to 32.5% with an average of 12.4%, while AgNORs counts ranged from 2.53/nucleus to 7.03/nucleus with an average of 4.74/nucleus. These four parameters were closely interrelated. There was a significant difference in PCNA score between malignant and nonmalignant lesions, suggesting a difference in growth activity. The mean PCNA score decreased significantly from 20.0% to 8.0% after cancer chemotherapy. The response of cancer cells to anticancer agents may be estimated by consecutive measurement of PCNA, since the PCNA score dropped after treatment in cases showing a favorable prognosis.", "contents": "Measurement of proliferating cell nuclear antigen (PCNA) and its clinical application in oral cancers. The PCNA score was measured in oral squamous cell carcinoma (SCC), and its relationship to other cell proliferation markers, Ki-67 score, S-phase fraction (SPF), and AgNORs counts was investigated. The PCNA score ranged from 0.4% to 43.5% with an average value of 22.8%, the Ki-67 score ranged from 4.9% to 40% with an average of 24.1%, and the SPF ranged from 0.4% to 32.5% with an average of 12.4%, while AgNORs counts ranged from 2.53/nucleus to 7.03/nucleus with an average of 4.74/nucleus. These four parameters were closely interrelated. There was a significant difference in PCNA score between malignant and nonmalignant lesions, suggesting a difference in growth activity. The mean PCNA score decreased significantly from 20.0% to 8.0% after cancer chemotherapy. The response of cancer cells to anticancer agents may be estimated by consecutive measurement of PCNA, since the PCNA score dropped after treatment in cases showing a favorable prognosis."} {"id": "PMID:1282925", "title": "The technical presentation.", "content": "A technical presentation, like any other presentation, requires organization so the audience can follow the speaker's core message smoothly and logically. Remember to incorporate these \"tips\" to make your technical presentation successful: Keep it short and simple (KISS) Using fewer visual aids is better Use large, bold and colorful, and unclutered visual aids Communicate with simplistic language Use vocal variety Use gestures Know your audience.", "contents": "The technical presentation. A technical presentation, like any other presentation, requires organization so the audience can follow the speaker's core message smoothly and logically. Remember to incorporate these \"tips\" to make your technical presentation successful: Keep it short and simple (KISS) Using fewer visual aids is better Use large, bold and colorful, and unclutered visual aids Communicate with simplistic language Use vocal variety Use gestures Know your audience."} {"id": "PMID:1282926", "title": "The human antibody V region repertoire to the type B capsular polysaccharide of Haemophilus influenzae.", "content": "The V region repertoire of the human antibody response to the type b capsular polysaccharide of Haemophilus influenzae (Hib-PS) is being defined at the molecular level using antibodies purified from serum of immunized adults. The VH of this response is restricted to the VHIII subgroup while the VL can be divided into two categories. The most common VL, expressed in > 90% of adults and usually constituting the majority of a subjects anti-Hib-PS antibody response, is restricted to the product of a single V kappa II gene known as A2 that probably lacks somatic mutations. The product of the A2 gene is invariably joined to one of several J kappa products by an inserted arginine at the V kappa-J kappa junction. In contrast to the restricted nature of the dominant VL clonotype, the second category of VL constitutes a heterogeneous group of at least seven different VL gene products that often contain somatic mutations and generally exhibit crossreactivity with a related polysaccharide from E. coli. Elucidation of anti-Hib-PS V regions at the molecular level will permit examination of structure-function relationships among these clinically important antibodies and should make the V region repertoire to Hib-PS a useful model for studying human V gene responses.", "contents": "The human antibody V region repertoire to the type B capsular polysaccharide of Haemophilus influenzae. The V region repertoire of the human antibody response to the type b capsular polysaccharide of Haemophilus influenzae (Hib-PS) is being defined at the molecular level using antibodies purified from serum of immunized adults. The VH of this response is restricted to the VHIII subgroup while the VL can be divided into two categories. The most common VL, expressed in > 90% of adults and usually constituting the majority of a subjects anti-Hib-PS antibody response, is restricted to the product of a single V kappa II gene known as A2 that probably lacks somatic mutations. The product of the A2 gene is invariably joined to one of several J kappa products by an inserted arginine at the V kappa-J kappa junction. In contrast to the restricted nature of the dominant VL clonotype, the second category of VL constitutes a heterogeneous group of at least seven different VL gene products that often contain somatic mutations and generally exhibit crossreactivity with a related polysaccharide from E. coli. Elucidation of anti-Hib-PS V regions at the molecular level will permit examination of structure-function relationships among these clinically important antibodies and should make the V region repertoire to Hib-PS a useful model for studying human V gene responses."} {"id": "PMID:1282927", "title": "Role of K+ channels in the modulation of cholinergic neural responses in guinea-pig and human airways.", "content": "1. Several agonists modulate cholinergic neurotransmission in airways raising the possibility that there may be a common inhibitory mechanism, such as the activation of a common K+ channel in the nerve ending. To test this hypothesis, we examined whether blockers of K+ channels are able to depress the prejunctional inhibitory modulation of cholinergic contractile responses by various agonists in guinea-pig and human airways in vitro. 2. Electrical field stimulation (40 V, 0.5 ms) was applied to guinea-pig (0.5 Hz) or human (1 Hz) tracheal strips every 4 min to elicit cholinergic neural responses. The effects of the K+ channel blockers, charybdotoxin (ChTX, 10 nM), apamin (100 nM) and glibenclamide (1 microM), on the prejunctional inhibition of cholinergic contraction evoked by neuropeptide Y (NPY, 100 nM), an alpha 2-agonist, clonidine (10 nM), a mu-opioid agonist, [D-Ala2, NMePhe4, Gly-ol5]-enkephalin (DAMGO, 100 nM), and a KATP channel opener, lemakalim (300 nM) were tested in guinea-pigs. In human tissues, the effect of ChTX (10 nM) on the mu-opioid (DAMGO, 300 nM)-induced inhibition of cholinergic nerves was examined. 3. In guinea-pigs, ChTX (10 nM) significantly reversed the prejunctional inhibition of cholinergic contraction by NPY (84.2 +/- 16.2%), clonidine (71.9 +/- 22.4%), DAMGO (67.3 +/- 13.1%) and lemakalim (20.9 +/- 9.4%) (n = 5, P < 0.05, respectively), while apamin (100 nM) had no effect. Glibenclamide (10 microM) reduced only the lemakalim-induced inhibitory modulation. ChTX (10 nM) itself potentiated cholinergic contraction (24.6 +/- 9.4%, n = 5, P < 0.05) without affecting exogenously applied acetylcholine dose-response curves. Pretreatment with ChTX (10 nM) significantly reduced the inhibitory modulation of cholinergic nerves by NPY, clonidine and DAMGO, but not by lemakalim. 4. In human tissues, ChTX significantly reduced DAMGO-induced prejunctional inhibition of cholinergic contraction (13.6 +/- 8.5% with and 46.5 +/- 5.5% without ChTX, respectively; n = 5, P < 0.05). 5. These results may support a hypothesis that the activation of ChTX-sensitive K+ channels is involved in the inhibitory modulation of cholinergic neuro-transmission by agonists acting on presynaptic receptors in guinea-pig and human airways.", "contents": "Role of K+ channels in the modulation of cholinergic neural responses in guinea-pig and human airways. 1. Several agonists modulate cholinergic neurotransmission in airways raising the possibility that there may be a common inhibitory mechanism, such as the activation of a common K+ channel in the nerve ending. To test this hypothesis, we examined whether blockers of K+ channels are able to depress the prejunctional inhibitory modulation of cholinergic contractile responses by various agonists in guinea-pig and human airways in vitro. 2. Electrical field stimulation (40 V, 0.5 ms) was applied to guinea-pig (0.5 Hz) or human (1 Hz) tracheal strips every 4 min to elicit cholinergic neural responses. The effects of the K+ channel blockers, charybdotoxin (ChTX, 10 nM), apamin (100 nM) and glibenclamide (1 microM), on the prejunctional inhibition of cholinergic contraction evoked by neuropeptide Y (NPY, 100 nM), an alpha 2-agonist, clonidine (10 nM), a mu-opioid agonist, [D-Ala2, NMePhe4, Gly-ol5]-enkephalin (DAMGO, 100 nM), and a KATP channel opener, lemakalim (300 nM) were tested in guinea-pigs. In human tissues, the effect of ChTX (10 nM) on the mu-opioid (DAMGO, 300 nM)-induced inhibition of cholinergic nerves was examined. 3. In guinea-pigs, ChTX (10 nM) significantly reversed the prejunctional inhibition of cholinergic contraction by NPY (84.2 +/- 16.2%), clonidine (71.9 +/- 22.4%), DAMGO (67.3 +/- 13.1%) and lemakalim (20.9 +/- 9.4%) (n = 5, P < 0.05, respectively), while apamin (100 nM) had no effect. Glibenclamide (10 microM) reduced only the lemakalim-induced inhibitory modulation. ChTX (10 nM) itself potentiated cholinergic contraction (24.6 +/- 9.4%, n = 5, P < 0.05) without affecting exogenously applied acetylcholine dose-response curves. Pretreatment with ChTX (10 nM) significantly reduced the inhibitory modulation of cholinergic nerves by NPY, clonidine and DAMGO, but not by lemakalim. 4. In human tissues, ChTX significantly reduced DAMGO-induced prejunctional inhibition of cholinergic contraction (13.6 +/- 8.5% with and 46.5 +/- 5.5% without ChTX, respectively; n = 5, P < 0.05). 5. These results may support a hypothesis that the activation of ChTX-sensitive K+ channels is involved in the inhibitory modulation of cholinergic neuro-transmission by agonists acting on presynaptic receptors in guinea-pig and human airways."} {"id": "PMID:1282928", "title": "Calcium homeostasis in the outer segments of retinal rods from the tiger salamander.", "content": "1. The processes regulating intracellular calcium in the outer segments of salamander rods have been investigated. The main preparation used was the isolated rod loaded with the Ca(2+)-sensitive photoprotein aequorin, from which outer segment membrane current and free [Ca2+]i could be recorded simultaneously. Two other preparations were also used: outer segment membrane current was recorded from intact, isolated rods using a suction pipette, and from detached outer segments using a whole-cell pipette. 2. Measurements of free intracellular [Ca2+] in Ringer solution were obtained from two aequorin-loaded rods. Mean [Ca2+]i in darkness was 0.41 microM, and after a bright flash [Ca2+]i fell to below detectable levels ( < 0.3 microM). No release of intracellular Ca2+ by a bright flash of light could be detected ( < 0.2 microM). 3. Application of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) caused an increase in the size of the light-sensitive current and a rise in [Ca2+]i, but application of IBMX either when the light-sensitive channels had been closed by a bright light or in the absence of external Ca2+ caused no detectable rise in [Ca2+]i. It is concluded that IBMX increases [Ca2+]i by opening light-sensitive channels, and does not release Ca2+ from stores within the outer segment. 4. Removal of external Na+ caused a rise in [Ca2+]i to around 2 microM and completely suppressed the light-sensitive current. 5. The Na(+)-Ca2+, K+ exchange current in aequorin-loaded rods was activated in first-order manner by internal free calcium, with a mean Michaelis constant, KCa, of 1.6 microM. 6. The KCa of the Na(+)-Ca2+, K+ exchange was increased by elevating internal [Na+]. 7. The Michaelis relation between [Ca2+]i and the activity of the Na(+)-Ca2+, K+ exchange was used to calculate the change in [Ca2+]i occurring during the response to a bright light. In aequorin-loaded rods in Ringer solution the mean change in free [Ca2+]i after a bright flash was 0.34 microM. In these rods 10% of the dark current was carried by Ca2+. 8. Most of the calcium entering the outer segment was taken up rapidly and reversibly by buffer systems. The time constant of equilibration between free and rapidly bound Ca2+ was less than 20 ms. No slow component of calcium uptake was detected. 9. Two components of calcium buffering could be distinguished in the outer segments of aequorin-loaded rods.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Calcium homeostasis in the outer segments of retinal rods from the tiger salamander. 1. The processes regulating intracellular calcium in the outer segments of salamander rods have been investigated. The main preparation used was the isolated rod loaded with the Ca(2+)-sensitive photoprotein aequorin, from which outer segment membrane current and free [Ca2+]i could be recorded simultaneously. Two other preparations were also used: outer segment membrane current was recorded from intact, isolated rods using a suction pipette, and from detached outer segments using a whole-cell pipette. 2. Measurements of free intracellular [Ca2+] in Ringer solution were obtained from two aequorin-loaded rods. Mean [Ca2+]i in darkness was 0.41 microM, and after a bright flash [Ca2+]i fell to below detectable levels ( < 0.3 microM). No release of intracellular Ca2+ by a bright flash of light could be detected ( < 0.2 microM). 3. Application of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) caused an increase in the size of the light-sensitive current and a rise in [Ca2+]i, but application of IBMX either when the light-sensitive channels had been closed by a bright light or in the absence of external Ca2+ caused no detectable rise in [Ca2+]i. It is concluded that IBMX increases [Ca2+]i by opening light-sensitive channels, and does not release Ca2+ from stores within the outer segment. 4. Removal of external Na+ caused a rise in [Ca2+]i to around 2 microM and completely suppressed the light-sensitive current. 5. The Na(+)-Ca2+, K+ exchange current in aequorin-loaded rods was activated in first-order manner by internal free calcium, with a mean Michaelis constant, KCa, of 1.6 microM. 6. The KCa of the Na(+)-Ca2+, K+ exchange was increased by elevating internal [Na+]. 7. The Michaelis relation between [Ca2+]i and the activity of the Na(+)-Ca2+, K+ exchange was used to calculate the change in [Ca2+]i occurring during the response to a bright light. In aequorin-loaded rods in Ringer solution the mean change in free [Ca2+]i after a bright flash was 0.34 microM. In these rods 10% of the dark current was carried by Ca2+. 8. Most of the calcium entering the outer segment was taken up rapidly and reversibly by buffer systems. The time constant of equilibration between free and rapidly bound Ca2+ was less than 20 ms. No slow component of calcium uptake was detected. 9. Two components of calcium buffering could be distinguished in the outer segments of aequorin-loaded rods.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282929", "title": "Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices.", "content": "1. Currents activated by glutamate receptor (GluR) agonists were recorded from outside-out patches isolated from the soma of visually identified pyramidal neurones of the CA3 and CA1 region of rat hippocampal slices. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), L-glutamate (L-Glu), and kainate (KA) were delivered either by bath application through perfusion of the recording chamber or by rapid application via a piezo-driven two-barrelled fast application system. 2. Bath application of each of the three agonists activated inward currents in all patches (n = 134) at holding potentials of -50 or -60 mV. The current amplitude increased in size between 3 to 30 microM-AMPA and 100 microM to 1 mM-KA. With this slow mode of bath application, the responses showed no apparent desensitization even at saturating concentrations of AMPA (30 microM) and KA (1 mM). 3. The ratio of currents activated by 30 microM-AMPA and 300 microM-KA showed a characteristic difference between CA3 and CA1 neurones. The ratio was 0.242 +/- 0.028 (mean +/- S.E.M., n = 16) for CA3 cell patches and 0.097 +/- 0.012 (n = 8) for CA1 cell patches indicating that GluRs in the two cell populations are different. 4. The steady-state current-voltage relations (I-Vs) for AMPA- and KA-activated currents showed pronounced outward rectification for both cell types (when the main cations are Na+ in the bath and Cs+ in the pipette solution). The current reversed close to 0 mV and the ratio of chord conductances 80 mV on either side of the reversal potential was 2.66 for KA-activated currents in CA3 cell patches and 2.60 in CA1 cell patches. AMPA-activated currents showed a time-dependent increase after steps to positive membrane potentials and a decrease after steps to negative voltages, indicating that a gating process is responsible for outward rectification of the steady-state I-V. 5. The permeability (P) of GluR channels was high for Na+ as compared to Cs+ for both cell types (PNa/PCs = 0.88 and 0.84). The permeability was low for N-methyl-D-glucamine+ (PNMG/PCs < or = 0.03) and Ca2+ (PCa/PCs < or = 0.05). 6. The current noise level increased during application of AMPA or KA. Apparent single-channel conductances obtained from fluctuation analysis were higher for AMPA than for KA, but similar for both cell types. In CA3 cell patches, AMPA activated channels with an apparent chord conductance of 7.2 pS, KA of 3.0 pS conductance.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Glutamate receptor channels in isolated patches from CA1 and CA3 pyramidal cells of rat hippocampal slices. 1. Currents activated by glutamate receptor (GluR) agonists were recorded from outside-out patches isolated from the soma of visually identified pyramidal neurones of the CA3 and CA1 region of rat hippocampal slices. alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), L-glutamate (L-Glu), and kainate (KA) were delivered either by bath application through perfusion of the recording chamber or by rapid application via a piezo-driven two-barrelled fast application system. 2. Bath application of each of the three agonists activated inward currents in all patches (n = 134) at holding potentials of -50 or -60 mV. The current amplitude increased in size between 3 to 30 microM-AMPA and 100 microM to 1 mM-KA. With this slow mode of bath application, the responses showed no apparent desensitization even at saturating concentrations of AMPA (30 microM) and KA (1 mM). 3. The ratio of currents activated by 30 microM-AMPA and 300 microM-KA showed a characteristic difference between CA3 and CA1 neurones. The ratio was 0.242 +/- 0.028 (mean +/- S.E.M., n = 16) for CA3 cell patches and 0.097 +/- 0.012 (n = 8) for CA1 cell patches indicating that GluRs in the two cell populations are different. 4. The steady-state current-voltage relations (I-Vs) for AMPA- and KA-activated currents showed pronounced outward rectification for both cell types (when the main cations are Na+ in the bath and Cs+ in the pipette solution). The current reversed close to 0 mV and the ratio of chord conductances 80 mV on either side of the reversal potential was 2.66 for KA-activated currents in CA3 cell patches and 2.60 in CA1 cell patches. AMPA-activated currents showed a time-dependent increase after steps to positive membrane potentials and a decrease after steps to negative voltages, indicating that a gating process is responsible for outward rectification of the steady-state I-V. 5. The permeability (P) of GluR channels was high for Na+ as compared to Cs+ for both cell types (PNa/PCs = 0.88 and 0.84). The permeability was low for N-methyl-D-glucamine+ (PNMG/PCs < or = 0.03) and Ca2+ (PCa/PCs < or = 0.05). 6. The current noise level increased during application of AMPA or KA. Apparent single-channel conductances obtained from fluctuation analysis were higher for AMPA than for KA, but similar for both cell types. In CA3 cell patches, AMPA activated channels with an apparent chord conductance of 7.2 pS, KA of 3.0 pS conductance.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282930", "title": "Dependence of electrical slow waves of canine colonic smooth muscle on calcium gradient.", "content": "1. The ionic dependence of the upstroke and plateau components of slow waves of canine colonic circular muscles was studied. 2. Reduced extracellular Ca2+ caused a decrease in the amplitude of the upstroke and plateau components, a decrease in the depolarization velocity, and a decrease in frequency. The reduction in the upstroke phase per 10-fold reduction in external Ca2+ was close to the value predicted by the Nernst relationship, suggesting that the membrane permeability to Ca2+ increases steeply during this phase. 3. Nifedipine (10(-9)-10(-6)) reduced the plateau component, but concentrations of 10(-6) M did not abolish the upstroke component. The data suggest that a nifedipine-resistant component of Ca2+ current may be involved in the upstroke. 4. Inorganic Ca2+ channel blockers (Mn2+ and Ni2+) blocked spontaneous slow waves at concentrations of 1.0 mM or less. 5. The upstroke component was more sensitive to Ni2+ than to Mn2+; a concentration of 0.040 mM-Ni2+ caused more than a 50% reduction in upstroke velocity. Ni2+ also reduced the plateau phase of slow waves. 6. The results suggest that the upstroke and plateau components of slow waves are dependent upon activation of voltage-dependent Ca2+ currents. The current responsible for the upstroke is partially resistant to dihydropyridines (at least at 10(-6) M). The current responsible for the plateau component is nifedipine-sensitive.", "contents": "Dependence of electrical slow waves of canine colonic smooth muscle on calcium gradient. 1. The ionic dependence of the upstroke and plateau components of slow waves of canine colonic circular muscles was studied. 2. Reduced extracellular Ca2+ caused a decrease in the amplitude of the upstroke and plateau components, a decrease in the depolarization velocity, and a decrease in frequency. The reduction in the upstroke phase per 10-fold reduction in external Ca2+ was close to the value predicted by the Nernst relationship, suggesting that the membrane permeability to Ca2+ increases steeply during this phase. 3. Nifedipine (10(-9)-10(-6)) reduced the plateau component, but concentrations of 10(-6) M did not abolish the upstroke component. The data suggest that a nifedipine-resistant component of Ca2+ current may be involved in the upstroke. 4. Inorganic Ca2+ channel blockers (Mn2+ and Ni2+) blocked spontaneous slow waves at concentrations of 1.0 mM or less. 5. The upstroke component was more sensitive to Ni2+ than to Mn2+; a concentration of 0.040 mM-Ni2+ caused more than a 50% reduction in upstroke velocity. Ni2+ also reduced the plateau phase of slow waves. 6. The results suggest that the upstroke and plateau components of slow waves are dependent upon activation of voltage-dependent Ca2+ currents. The current responsible for the upstroke is partially resistant to dihydropyridines (at least at 10(-6) M). The current responsible for the plateau component is nifedipine-sensitive."} {"id": "PMID:1282931", "title": "Upstroke component of electrical slow waves in canine colonic smooth muscle due to nifedipine-resistant calcium current.", "content": "1. Electrical slow waves of gastrointestinal smooth muscles are not abolished by organic Ca2+ channel blocking drugs, such as nifedipine or D600. These compounds reduce the amplitude and duration of the plateau phase, but the upstroke phase of slow waves persists. 2. Voltage clamp experiments were performed on isolated circular muscle cells from the canine proximal colon to characterize the dihydropyridine-resistant component of inward current. Inward currents were measured at 25 and 35 degrees C. The higher temperature increased the amplitudes of the transient and sustained phases of the inward current. The voltage dependence of activation and inactivation of the inward current was not significantly changed at 35 vs. 25 degrees C. 3. At 35 degrees C the transient phase of the inward current was reduced but not blocked by nifedipine (10(-6) M). The sustained phase was blocked by nifedipine. 4. The block by nifedipine was voltage dependent, increasing with depolarization. At voltages reached during the upstroke depolarization about 35% of the inward current persisted in the presence of nifedipine (10(-6) M). This may be sufficient inward current to sustain the upstroke depolarization in intact muscles. 5. Nifedipine caused a 20 mV negative shift in the voltage dependence of inactivation suggesting that dihydropyridines may preferentially bind to Ca2+ channels in an inactivated state. 6. Ni2+ (< 100 microM) significantly decreased the transient phase of inward current. A combination of Ni2+ (40 microM) and nifedipine (10(-6) M) blocked all of the inward current at 35 degrees C. Combination of nifedipine (10(-6) M) and Ni2+ (40 microM) blocked slow waves in intact muscles. 7. Bay K 8644 (10(-6) M) increased the amplitude of the transient and sustained components of inward current. On a percentage basis the increase in the sustained component was greater than the increase in the transient component with test potentials in the range of -50 to -20 mV. This may explain why Bay K 8644 preferentially increases the plateau component of slow waves vs. the upstroke component. 8. The findings of this study suggest that the nifedipine resistance of the upstroke depolarization could be due to the voltage dependence of the block of Ca2+ channels by dihydropyridines. Thus a single class of voltage-dependent Ca2+ channels could be responsible for the upstroke and plateau phases of slow waves.", "contents": "Upstroke component of electrical slow waves in canine colonic smooth muscle due to nifedipine-resistant calcium current. 1. Electrical slow waves of gastrointestinal smooth muscles are not abolished by organic Ca2+ channel blocking drugs, such as nifedipine or D600. These compounds reduce the amplitude and duration of the plateau phase, but the upstroke phase of slow waves persists. 2. Voltage clamp experiments were performed on isolated circular muscle cells from the canine proximal colon to characterize the dihydropyridine-resistant component of inward current. Inward currents were measured at 25 and 35 degrees C. The higher temperature increased the amplitudes of the transient and sustained phases of the inward current. The voltage dependence of activation and inactivation of the inward current was not significantly changed at 35 vs. 25 degrees C. 3. At 35 degrees C the transient phase of the inward current was reduced but not blocked by nifedipine (10(-6) M). The sustained phase was blocked by nifedipine. 4. The block by nifedipine was voltage dependent, increasing with depolarization. At voltages reached during the upstroke depolarization about 35% of the inward current persisted in the presence of nifedipine (10(-6) M). This may be sufficient inward current to sustain the upstroke depolarization in intact muscles. 5. Nifedipine caused a 20 mV negative shift in the voltage dependence of inactivation suggesting that dihydropyridines may preferentially bind to Ca2+ channels in an inactivated state. 6. Ni2+ (< 100 microM) significantly decreased the transient phase of inward current. A combination of Ni2+ (40 microM) and nifedipine (10(-6) M) blocked all of the inward current at 35 degrees C. Combination of nifedipine (10(-6) M) and Ni2+ (40 microM) blocked slow waves in intact muscles. 7. Bay K 8644 (10(-6) M) increased the amplitude of the transient and sustained components of inward current. On a percentage basis the increase in the sustained component was greater than the increase in the transient component with test potentials in the range of -50 to -20 mV. This may explain why Bay K 8644 preferentially increases the plateau component of slow waves vs. the upstroke component. 8. The findings of this study suggest that the nifedipine resistance of the upstroke depolarization could be due to the voltage dependence of the block of Ca2+ channels by dihydropyridines. Thus a single class of voltage-dependent Ca2+ channels could be responsible for the upstroke and plateau phases of slow waves."} {"id": "PMID:1282932", "title": "A patch clamp study of the nicotinic acetylcholine receptor of bovine adrenomedullary chromaffin cells in culture.", "content": "1. Acetylcholine-induced currents recorded from bovine adrenal medullary chromaffin cells maintained in culture were studied during pressure or ionophoretic applications of ACh, using the 'whole-cell' and 'outside-out' configurations of the patch clamp technique. In standard salines, ACh evoked whole-cell currents of -38 pA to -1 nA at -60 mV, which had a reversal potential (EACh) of -7.1 +/- 0.6 mV. The ACh current-voltage relationship was characteristically linear at negative holding potentials and biphasic at positive holding potentials, displaying a region of almost zero slope conductance between 0 and +40 mV followed by a region of positive slope conductance at more positive potentials. 2. Relative permeation to cations was examined. Substitution of external Na+ by sucrose resulted in a -42 mV shift of EACh for a 10-fold reduction in [Na+]o. Using isotonic substitutions, the permeability ratios (relative to Na+) for monovalent cations were determined to be 1.32 +/- 0.02 for Cs+ (n = 11), 1.03 +/- 0.02 for Li+ (n = 8) and 0.18 +/- 0.02 for Tris+ (n = 7). Elevated external Ca2+ salines were found to shift EACh to more positive potentials, especially in the presence of low external Na+. 3. The nicotinic agonists nicotine, tetramethylammonium and lobeline evoked inward currents in bovine chromaffin cells. In contrast, decamethonium and the muscarinic agonist, methacholine, had no effect. 4. The nicotinic antagonists mecamylamine, trimetaphan, (+)-tubocurarine and hexamethonium caused dose-dependent reductions in the amplitude of ACh-evoked inward currents. The estimated IC50's were 0.25, 0.33, 0.63 and 2.2 microM respectively, for cells voltage clamped at -60 mV. High concentrations (> 2 microM) of the muscarinic antagonist, atropine, also produced a dose-dependent reduction in the amplitude of ACh-induced currents. 5. Inhibition by trimetaphan was voltage independent. With the other drugs the antagonism was voltage sensitive, increasing with membrane hyperpolarization. The voltage sensitivity was most marked for hexamethonium. Neither hexamethonium nor mecamylamine were found to depress ACh-evoked outward currents at concentrations which severely depressed inward currents. In addition to its antagonist actions, (+)-tubocurarine activated unitary currents in these cells and on isolated membrane patches. 6. The results indicate that nicotinic ion channels of bovine chromaffin cells have a similar ionic selectivity to monovalent cations, but that Ca2+ ions permeate the channels to a greater degree than at the motor endplate. The ACh current-voltage relationship resembles that described for other types of 'neuronal' nicotinic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "A patch clamp study of the nicotinic acetylcholine receptor of bovine adrenomedullary chromaffin cells in culture. 1. Acetylcholine-induced currents recorded from bovine adrenal medullary chromaffin cells maintained in culture were studied during pressure or ionophoretic applications of ACh, using the 'whole-cell' and 'outside-out' configurations of the patch clamp technique. In standard salines, ACh evoked whole-cell currents of -38 pA to -1 nA at -60 mV, which had a reversal potential (EACh) of -7.1 +/- 0.6 mV. The ACh current-voltage relationship was characteristically linear at negative holding potentials and biphasic at positive holding potentials, displaying a region of almost zero slope conductance between 0 and +40 mV followed by a region of positive slope conductance at more positive potentials. 2. Relative permeation to cations was examined. Substitution of external Na+ by sucrose resulted in a -42 mV shift of EACh for a 10-fold reduction in [Na+]o. Using isotonic substitutions, the permeability ratios (relative to Na+) for monovalent cations were determined to be 1.32 +/- 0.02 for Cs+ (n = 11), 1.03 +/- 0.02 for Li+ (n = 8) and 0.18 +/- 0.02 for Tris+ (n = 7). Elevated external Ca2+ salines were found to shift EACh to more positive potentials, especially in the presence of low external Na+. 3. The nicotinic agonists nicotine, tetramethylammonium and lobeline evoked inward currents in bovine chromaffin cells. In contrast, decamethonium and the muscarinic agonist, methacholine, had no effect. 4. The nicotinic antagonists mecamylamine, trimetaphan, (+)-tubocurarine and hexamethonium caused dose-dependent reductions in the amplitude of ACh-evoked inward currents. The estimated IC50's were 0.25, 0.33, 0.63 and 2.2 microM respectively, for cells voltage clamped at -60 mV. High concentrations (> 2 microM) of the muscarinic antagonist, atropine, also produced a dose-dependent reduction in the amplitude of ACh-induced currents. 5. Inhibition by trimetaphan was voltage independent. With the other drugs the antagonism was voltage sensitive, increasing with membrane hyperpolarization. The voltage sensitivity was most marked for hexamethonium. Neither hexamethonium nor mecamylamine were found to depress ACh-evoked outward currents at concentrations which severely depressed inward currents. In addition to its antagonist actions, (+)-tubocurarine activated unitary currents in these cells and on isolated membrane patches. 6. The results indicate that nicotinic ion channels of bovine chromaffin cells have a similar ionic selectivity to monovalent cations, but that Ca2+ ions permeate the channels to a greater degree than at the motor endplate. The ACh current-voltage relationship resembles that described for other types of 'neuronal' nicotinic receptors.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1282933", "title": "The gp120 glycoprotein of HIV-1 binds to sulfatide and to the myelin associated glycoprotein.", "content": "We investigated the binding of the gp120 glycoprotein of the human immunodeficiency virus (HIV-1) to neural glycolipids and glycoproteins by ELISA. The gp120 protein bound to sulfatide (GalS), a sulfated glycolipid autoantigen implicated in sensory neuritis, and to the myelin associated glycoprotein (MAG), an autoantigen in demyelinating neuropathy. Binding of gp120 to MAG was inhibited by the HNK-1 antibody, which recognizes a sulfated glucuronic acid epitope, suggesting that the interaction involves carbohydrate determinants. Sulfatide and MAG are potential receptors for gp120 in peripheral nerve and may have a role in the neuropathy associated with HIV-1 infection.", "contents": "The gp120 glycoprotein of HIV-1 binds to sulfatide and to the myelin associated glycoprotein. We investigated the binding of the gp120 glycoprotein of the human immunodeficiency virus (HIV-1) to neural glycolipids and glycoproteins by ELISA. The gp120 protein bound to sulfatide (GalS), a sulfated glycolipid autoantigen implicated in sensory neuritis, and to the myelin associated glycoprotein (MAG), an autoantigen in demyelinating neuropathy. Binding of gp120 to MAG was inhibited by the HNK-1 antibody, which recognizes a sulfated glucuronic acid epitope, suggesting that the interaction involves carbohydrate determinants. Sulfatide and MAG are potential receptors for gp120 in peripheral nerve and may have a role in the neuropathy associated with HIV-1 infection."} {"id": "PMID:1282934", "title": "Specific binding of cytotactin to sulfated glycolipids.", "content": "The binding of the glial glycoprotein, cytotactin, to a variety of purified glycolipids was examined. Clear-cut evidence was found for binding of radiolabeled cytotactin to sulfatides purified from bovine brain, but the molecule did not bind to gangliosides or cerebrosides. The sulfatide binding was sensitive to pH and ionic strength and was dependent on the presence of divalent cations. Binding was inhibited by purified unlabeled cytotactin, by polyclonal antibodies to cytotactin, and by several monosaccharides and polysaccharides. It was not inhibited by fibronectin, a chondroitin sulfate proteoglycan, or the HNK-1 monoclonal antibody, all of which are known to bind to cytotactin. These findings raise the possibilities that sulfated glycolipids may function as cellular receptors for cytotactin and that binding by sulfatides may modulate the varied effects of cytotactin on cellular processes.", "contents": "Specific binding of cytotactin to sulfated glycolipids. The binding of the glial glycoprotein, cytotactin, to a variety of purified glycolipids was examined. Clear-cut evidence was found for binding of radiolabeled cytotactin to sulfatides purified from bovine brain, but the molecule did not bind to gangliosides or cerebrosides. The sulfatide binding was sensitive to pH and ionic strength and was dependent on the presence of divalent cations. Binding was inhibited by purified unlabeled cytotactin, by polyclonal antibodies to cytotactin, and by several monosaccharides and polysaccharides. It was not inhibited by fibronectin, a chondroitin sulfate proteoglycan, or the HNK-1 monoclonal antibody, all of which are known to bind to cytotactin. These findings raise the possibilities that sulfated glycolipids may function as cellular receptors for cytotactin and that binding by sulfatides may modulate the varied effects of cytotactin on cellular processes."} {"id": "PMID:1282935", "title": "L2/HNK-1 carbohydrate and protein-protein interactions mediate the homophilic binding of the neural adhesion molecule P0.", "content": "The neural adhesion molecule P0, the most abundant glycoprotein in peripheral myelin of mammals, is a member of the immunoglobulin superfamily and expresses the L2/HNK-1 and L3 oligosaccharides at a single N-glycosylation site. It acts in both homophilic and heterophilic binding mechanisms. To investigate the molecular requirements for homophilic interaction, we have used P0 from human sciatic nerve and the extracellular domain of P0 expressed in bacteria to determine binding of P0 to P0 in solid phase and bead aggregation assays. The binding of P0 to P0 could be partially inhibited in both assays by antibodies to the L2/HNK-1 epitope and by the L2/HNK-1 carbohydrate, but not by L3 antibodies or other carbohydrates. Inhibition of binding was also seen with polyclonal antibodies reacting with the protein backbone of P0. These observations indicate that both carbohydrate and protein structures are involved in the binding of P0 to P0 and that P0 acts as a presenter of and a receptor for a functionally important carbohydrate.", "contents": "L2/HNK-1 carbohydrate and protein-protein interactions mediate the homophilic binding of the neural adhesion molecule P0. The neural adhesion molecule P0, the most abundant glycoprotein in peripheral myelin of mammals, is a member of the immunoglobulin superfamily and expresses the L2/HNK-1 and L3 oligosaccharides at a single N-glycosylation site. It acts in both homophilic and heterophilic binding mechanisms. To investigate the molecular requirements for homophilic interaction, we have used P0 from human sciatic nerve and the extracellular domain of P0 expressed in bacteria to determine binding of P0 to P0 in solid phase and bead aggregation assays. The binding of P0 to P0 could be partially inhibited in both assays by antibodies to the L2/HNK-1 epitope and by the L2/HNK-1 carbohydrate, but not by L3 antibodies or other carbohydrates. Inhibition of binding was also seen with polyclonal antibodies reacting with the protein backbone of P0. These observations indicate that both carbohydrate and protein structures are involved in the binding of P0 to P0 and that P0 acts as a presenter of and a receptor for a functionally important carbohydrate."} {"id": "PMID:1282936", "title": "[Detection of glycosylated protein of renal tissues using NBT reaction in STZ-induced diabetic rats].", "content": "We are carried out to determine the detection of glycosylated protein of renal tissues using nitroblue tetrazolium (NBT) reaction in streptozotocin (STZ)-induced diabetic rats. The levels of glomerular non-enzymatic glycosylation were measured by thiobarbituric acid (TBA) method. There was no significant difference in the intensity of NBT in renal tissues between the 4-week diabetic rats and the same age control rats. The intensity of NBT in the glomerular mesangial areas and capillary walls was marked in 12-week diabetic rats. The staining of NBT was also observed in the tubular epithelial cells in 4- and 12-week diabetic rats. The levels of glomerular non-enzymatic glycosylated protein in 4- or 12-week diabetic rats were significantly greater than those in the same age control rats. It appears that the non-enzymatic glycosylation of renal tissues increased in the early stage of diabetic nephropathy, i.e. 4- or 12-week diabetic rats. It is concluded that the non-enzymatic glycosylation may play an important role in the initiation of renal injuries in diabetic nephropathy.", "contents": "[Detection of glycosylated protein of renal tissues using NBT reaction in STZ-induced diabetic rats]. We are carried out to determine the detection of glycosylated protein of renal tissues using nitroblue tetrazolium (NBT) reaction in streptozotocin (STZ)-induced diabetic rats. The levels of glomerular non-enzymatic glycosylation were measured by thiobarbituric acid (TBA) method. There was no significant difference in the intensity of NBT in renal tissues between the 4-week diabetic rats and the same age control rats. The intensity of NBT in the glomerular mesangial areas and capillary walls was marked in 12-week diabetic rats. The staining of NBT was also observed in the tubular epithelial cells in 4- and 12-week diabetic rats. The levels of glomerular non-enzymatic glycosylated protein in 4- or 12-week diabetic rats were significantly greater than those in the same age control rats. It appears that the non-enzymatic glycosylation of renal tissues increased in the early stage of diabetic nephropathy, i.e. 4- or 12-week diabetic rats. It is concluded that the non-enzymatic glycosylation may play an important role in the initiation of renal injuries in diabetic nephropathy."} {"id": "PMID:1282938", "title": "Molecular cloning of human endothelin (ET) receptors ETA and ETB.", "content": "Complementary DNAs coding for two different endothelin (ET) receptors were isolated from a human lung cDNA library. DNA sequencing revealed that they corresponded to either the ET-1-selective receptor subtype originally identified in cows (ETA) or the nonselective subtype first found in rats (ETB). An open reading frame coding for a 427 (ETA) or a 442 (ETB) amino acid-long protein, with a transmembrane topology also found in other G protein-coupled receptors, was determined. Whereas the amino acid identity is about 90% between the characterized members of a given receptor subtype, with the best conserved parts being the hydrophobic transmembrane domains, less than 60% identity was found between the human A and B subtypes. Southern blot analysis of human genomic DNA revealed the existence of multiple hybridizing bands when using probes derived from the full-length ETA or ETB cDNAs. However, when shorter fragments were selected as probes, only one band remained detectable, which suggests the existence of a single-copy gene for each subtype of ET receptor.", "contents": "Molecular cloning of human endothelin (ET) receptors ETA and ETB. Complementary DNAs coding for two different endothelin (ET) receptors were isolated from a human lung cDNA library. DNA sequencing revealed that they corresponded to either the ET-1-selective receptor subtype originally identified in cows (ETA) or the nonselective subtype first found in rats (ETB). An open reading frame coding for a 427 (ETA) or a 442 (ETB) amino acid-long protein, with a transmembrane topology also found in other G protein-coupled receptors, was determined. Whereas the amino acid identity is about 90% between the characterized members of a given receptor subtype, with the best conserved parts being the hydrophobic transmembrane domains, less than 60% identity was found between the human A and B subtypes. Southern blot analysis of human genomic DNA revealed the existence of multiple hybridizing bands when using probes derived from the full-length ETA or ETB cDNAs. However, when shorter fragments were selected as probes, only one band remained detectable, which suggests the existence of a single-copy gene for each subtype of ET receptor."} {"id": "PMID:1282939", "title": "Bradykinin-induced, N omega-nitro-L-arginine-insensitive endothelium-dependent relaxation of porcine coronary arteries is not mediated by bioassayable relaxing substances.", "content": "The effect of the arginine analogue, N omega-nitro-L-arginine (L-NNA) was studied on bradykinin-induced relaxation in porcine coronary arteries. In the presence of indomethacin (3 x 10(-6) M) and captopril (10(-6) M), treatment with L-NNA (10(-4) M) had no effect on the bradykinin-induced (10(-10)-10(-7) M) relaxations in strips contracted with U-46619. In contrast to the findings in organ chamber experiments, bradykinin-induced release of endothelium-derived relaxing factor(s) (EDRFs) was abolished after 45 min of treatment of perfused porcine coronary artery segments with L-NNA (10(-4) M) in a superfusion bioassay system. These results show that, in addition to the release of nitric oxide, endothelium-dependent relaxation of porcine coronary arteries to bradykinin involves an alternative mechanism(s), which accounts for the relaxation in the presence of L-NNA. Since the release of a relaxing mediator could not be detected from L-NNA-treated porcine coronary artery segments under bioassay conditions, it is postulated that either no diffusible factor(s) is involved in the L-NNA-insensitive endothelium-dependent relaxation, or it is mediated by an extremely labile endothelium-derived substance(s).", "contents": "Bradykinin-induced, N omega-nitro-L-arginine-insensitive endothelium-dependent relaxation of porcine coronary arteries is not mediated by bioassayable relaxing substances. The effect of the arginine analogue, N omega-nitro-L-arginine (L-NNA) was studied on bradykinin-induced relaxation in porcine coronary arteries. In the presence of indomethacin (3 x 10(-6) M) and captopril (10(-6) M), treatment with L-NNA (10(-4) M) had no effect on the bradykinin-induced (10(-10)-10(-7) M) relaxations in strips contracted with U-46619. In contrast to the findings in organ chamber experiments, bradykinin-induced release of endothelium-derived relaxing factor(s) (EDRFs) was abolished after 45 min of treatment of perfused porcine coronary artery segments with L-NNA (10(-4) M) in a superfusion bioassay system. These results show that, in addition to the release of nitric oxide, endothelium-dependent relaxation of porcine coronary arteries to bradykinin involves an alternative mechanism(s), which accounts for the relaxation in the presence of L-NNA. Since the release of a relaxing mediator could not be detected from L-NNA-treated porcine coronary artery segments under bioassay conditions, it is postulated that either no diffusible factor(s) is involved in the L-NNA-insensitive endothelium-dependent relaxation, or it is mediated by an extremely labile endothelium-derived substance(s)."} {"id": "PMID:1282940", "title": "N omega-nitro-L-arginine blocks the second phase but not the first phase of the endothelium-dependent relaxations induced by substance P in isolated rings of pig carotid artery.", "content": "Endothelium-dependent relaxations can be evoked by a variety of stimuli, among them substance P (SP), which is found in sensory nerve fibers supplying the adventitia-media junction of most muscular arteries. This study determined the role of endothelium-derived nitric oxide as a mediator of endothelium-dependent relaxations to SP in isolated rings of the pig carotid artery suspended in organ chambers for isometric tension recording. SP (10(-12)-10(-7) M) caused concentration-dependent relaxations of arteries precontracted with norepinephrine (10(-7) M). The relaxations were characterized by a partially transient relaxation (phase 1) and a sustained relaxation of the artery (phase 2). The inhibitor of nitric oxide formation, N omega-nitro-L-arginine (L-NNA) methyl ester caused a gradual increase in tension, the phase I response at 3 x 10(-10) to 3 x 10(-7) M SP was shifted to the right, but the maximal relaxation was comparable in the presence of L-NNA. However, the sustained relaxation after addition of substance P (phase II) was lost and tension in the presence of L-NNA returned to a level above that induced by L-NNA and norepinephrine (10(-9) M). These results suggest that the endothelium-dependent relaxations to SP, particularly the prolonged relaxation (phase II), are due to de novo synthesis of nitric oxide and hence fully abolished by a specific inhibitor.", "contents": "N omega-nitro-L-arginine blocks the second phase but not the first phase of the endothelium-dependent relaxations induced by substance P in isolated rings of pig carotid artery. Endothelium-dependent relaxations can be evoked by a variety of stimuli, among them substance P (SP), which is found in sensory nerve fibers supplying the adventitia-media junction of most muscular arteries. This study determined the role of endothelium-derived nitric oxide as a mediator of endothelium-dependent relaxations to SP in isolated rings of the pig carotid artery suspended in organ chambers for isometric tension recording. SP (10(-12)-10(-7) M) caused concentration-dependent relaxations of arteries precontracted with norepinephrine (10(-7) M). The relaxations were characterized by a partially transient relaxation (phase 1) and a sustained relaxation of the artery (phase 2). The inhibitor of nitric oxide formation, N omega-nitro-L-arginine (L-NNA) methyl ester caused a gradual increase in tension, the phase I response at 3 x 10(-10) to 3 x 10(-7) M SP was shifted to the right, but the maximal relaxation was comparable in the presence of L-NNA. However, the sustained relaxation after addition of substance P (phase II) was lost and tension in the presence of L-NNA returned to a level above that induced by L-NNA and norepinephrine (10(-9) M). These results suggest that the endothelium-dependent relaxations to SP, particularly the prolonged relaxation (phase II), are due to de novo synthesis of nitric oxide and hence fully abolished by a specific inhibitor."} {"id": "PMID:1282941", "title": "Biphasic response to substance P in canine basilar arteries.", "content": "The responses to intraluminally applied substance P (SP) were examined in isolated and perfused canine basilar arteries using the stainless-steel cannula inserting method. In control vessels with intact endothelium, this peptide induced a monophasic dilation at lower doses, and a biphasic response, i.e., an initial dilation followed by a secondary constriction at higher doses. After extraluminal treatment with oxyhemoglobin, the dilation was attenuated and the constriction was augmented. After endothelial removal with intraluminal saponin, the dilation was reduced and the constriction was enhanced significantly. This potentiated constriction was significantly depressed by indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane synthetase inhibitor), and nimodipine (a calcium antagonist), but not by AA-861 (a lipoxygenase inhibitor). These results suggest that SP has two distinct effects (an endothelium-dependent dilation and a direct constriction) and that the potentiated constriction in the absence of endothelium may be related to the action of thromboxane A2, linked with calcium influx into the smooth muscle cells of cerebral arteries. This mechanism may be implicated in cerebral vasospasm after subarachnoid hemorrhage.", "contents": "Biphasic response to substance P in canine basilar arteries. The responses to intraluminally applied substance P (SP) were examined in isolated and perfused canine basilar arteries using the stainless-steel cannula inserting method. In control vessels with intact endothelium, this peptide induced a monophasic dilation at lower doses, and a biphasic response, i.e., an initial dilation followed by a secondary constriction at higher doses. After extraluminal treatment with oxyhemoglobin, the dilation was attenuated and the constriction was augmented. After endothelial removal with intraluminal saponin, the dilation was reduced and the constriction was enhanced significantly. This potentiated constriction was significantly depressed by indomethacin (a cyclooxygenase inhibitor), OKY-046 (a thromboxane synthetase inhibitor), and nimodipine (a calcium antagonist), but not by AA-861 (a lipoxygenase inhibitor). These results suggest that SP has two distinct effects (an endothelium-dependent dilation and a direct constriction) and that the potentiated constriction in the absence of endothelium may be related to the action of thromboxane A2, linked with calcium influx into the smooth muscle cells of cerebral arteries. This mechanism may be implicated in cerebral vasospasm after subarachnoid hemorrhage."} {"id": "PMID:1282942", "title": "In vitro biological profile of a highly potent novel endothelin (ET) antagonist BQ-123 selective for the ETA receptor.", "content": "The novel endothelin (ET) receptor antagonists BE-18257A and BE-18257B were isolated from the fermentation products of Streptomyces misakiensis. The above-mentioned compounds inhibited [125I]ET-1 binding to ETA receptors (selective for ET-1) on porcine aortic vascular smooth muscle cells (VSMCs) with IC50 values of 1.4 and 0.47 microM, respectively. [125I]ET-1 binding to ETB receptors (nonselective to ET isopeptides) in cerebellar membranes was not inhibited by either of these compounds even at 100 microM. The synthesized analogue BQ-123 induced extremely potent inhibition of [125I]ET-1 binding to ETA receptors (IC50 of 7.3 nM), but it barely inhibited [125I]ET-1 binding to ETB receptors (IC50 of 18 microM) and binding of various other peptides to their receptors. BQ-123 shifted the concentration-response curve for ET-1 toward the right in porcine isolated coronary arteries, indicative of competitive antagonism for the ETA receptor. However, there was a small amount of BQ-123-insensitive vasoconstriction that paralleled the incomplete inhibition of [125I]ET-1 binding in the membrane of the vascular smooth muscle layer. These data suggest that the artery contracts via both ETA and ETB receptors and that BQ-123 selectively inhibits ETA-mediated contraction. Furthermore, BQ-123 revealed large tissue and species differences in the distribution of ETA receptors. Thus, the potent ETA antagonist BQ-123 should be useful in clarifying the (patho)physiological roles of ETA receptors.", "contents": "In vitro biological profile of a highly potent novel endothelin (ET) antagonist BQ-123 selective for the ETA receptor. The novel endothelin (ET) receptor antagonists BE-18257A and BE-18257B were isolated from the fermentation products of Streptomyces misakiensis. The above-mentioned compounds inhibited [125I]ET-1 binding to ETA receptors (selective for ET-1) on porcine aortic vascular smooth muscle cells (VSMCs) with IC50 values of 1.4 and 0.47 microM, respectively. [125I]ET-1 binding to ETB receptors (nonselective to ET isopeptides) in cerebellar membranes was not inhibited by either of these compounds even at 100 microM. The synthesized analogue BQ-123 induced extremely potent inhibition of [125I]ET-1 binding to ETA receptors (IC50 of 7.3 nM), but it barely inhibited [125I]ET-1 binding to ETB receptors (IC50 of 18 microM) and binding of various other peptides to their receptors. BQ-123 shifted the concentration-response curve for ET-1 toward the right in porcine isolated coronary arteries, indicative of competitive antagonism for the ETA receptor. However, there was a small amount of BQ-123-insensitive vasoconstriction that paralleled the incomplete inhibition of [125I]ET-1 binding in the membrane of the vascular smooth muscle layer. These data suggest that the artery contracts via both ETA and ETB receptors and that BQ-123 selectively inhibits ETA-mediated contraction. Furthermore, BQ-123 revealed large tissue and species differences in the distribution of ETA receptors. Thus, the potent ETA antagonist BQ-123 should be useful in clarifying the (patho)physiological roles of ETA receptors."} {"id": "PMID:1282943", "title": "Endothelium-dependent contraction produced by acetylcholine and relaxation produced by histamine in monkey basilar arteries.", "content": "The present experiments were carried out to investigate the endothelium dependence of the responses to acetylcholine (ACh), arachidonic acid, and histamine in monkey basilar arteries. ACh and arachidonic acid caused endothelium-dependent contraction (EC) in both monkey and canine basilar arteries. The endothelium-derived contracting factor (EDCF) was probably thromboxane A2 (TxA2), as the EDC was attenuated by a cyclooxygenase inhibitor, TxA2 synthetase inhibitors, and TxA2 antagonists. On the other hand, histamine caused endothelium-dependent relaxation (EDR) in monkey and EDC in canine basilar arteries. The EDR in monkey basilar arteries was attenuated by a nitric oxide synthase inhibitor. The EDR and EDC were antagonized by tripelennamine but not by cimetidine, indicating that they are mediated by H1-receptors. From these results, we suggest that in the monkey basilar artery, either there are two types of endothelium (an EDCF type for ACh and arachidonic acid and an EDRF type for histamine) or there is a single type of endothelium with two types of signalling processes (one for EDC and one for EDR).", "contents": "Endothelium-dependent contraction produced by acetylcholine and relaxation produced by histamine in monkey basilar arteries. The present experiments were carried out to investigate the endothelium dependence of the responses to acetylcholine (ACh), arachidonic acid, and histamine in monkey basilar arteries. ACh and arachidonic acid caused endothelium-dependent contraction (EC) in both monkey and canine basilar arteries. The endothelium-derived contracting factor (EDCF) was probably thromboxane A2 (TxA2), as the EDC was attenuated by a cyclooxygenase inhibitor, TxA2 synthetase inhibitors, and TxA2 antagonists. On the other hand, histamine caused endothelium-dependent relaxation (EDR) in monkey and EDC in canine basilar arteries. The EDR in monkey basilar arteries was attenuated by a nitric oxide synthase inhibitor. The EDR and EDC were antagonized by tripelennamine but not by cimetidine, indicating that they are mediated by H1-receptors. From these results, we suggest that in the monkey basilar artery, either there are two types of endothelium (an EDCF type for ACh and arachidonic acid and an EDRF type for histamine) or there is a single type of endothelium with two types of signalling processes (one for EDC and one for EDR)."} {"id": "PMID:1282944", "title": "Different mechanisms of hypoxic relaxation in canine coronary arteries and rat abdominal aortas.", "content": "Hypoxia causes complex changes in vascular tone of isolated blood vessels. This study was performed in rings with and without endothelium of rat abdominal aortas and canine coronary arteries suspended in organ chambers for isometric tension recording. In both aortic and coronary rings with endothelium precontracted with a half-maximal concentration of phenylephrine or prostaglandin F2 alpha, respectively, hypoxia induced transient relaxations (20 +/- 2 and 15 +/- 3%, respectively); removal of the endothelium prevented the response in aortas, but not coronary arteries. The transient hypoxic relaxation was followed in both preparations by endothelium-dependent contractions (EDCs). Hypoxic relaxations were prevented by indomethacin (10 microM) in canine arteries, but not in rat aortas. The inhibitor of nitric oxide (NO) synthase, N omega-nitro-L-arginine (30 microM), inhibited hypoxic relaxations in intact rat aortas, but left those in coronary arteries unchanged. Similar results were obtained with methylene blue and LY 83583. In preparations without endothelium, sodium nitroprusside (30 nM) elicited a reappearance of hypoxic relaxations in the rat but not the dog coronary artery. Thus, hypoxic relaxation is mediated by a prostaglandin in the dog coronary artery, but by endothelium-derived NO in the rat aorta. As the response was dependent on the level of contraction, this suggests that the release or action of NO decreases with increasing tone.", "contents": "Different mechanisms of hypoxic relaxation in canine coronary arteries and rat abdominal aortas. Hypoxia causes complex changes in vascular tone of isolated blood vessels. This study was performed in rings with and without endothelium of rat abdominal aortas and canine coronary arteries suspended in organ chambers for isometric tension recording. In both aortic and coronary rings with endothelium precontracted with a half-maximal concentration of phenylephrine or prostaglandin F2 alpha, respectively, hypoxia induced transient relaxations (20 +/- 2 and 15 +/- 3%, respectively); removal of the endothelium prevented the response in aortas, but not coronary arteries. The transient hypoxic relaxation was followed in both preparations by endothelium-dependent contractions (EDCs). Hypoxic relaxations were prevented by indomethacin (10 microM) in canine arteries, but not in rat aortas. The inhibitor of nitric oxide (NO) synthase, N omega-nitro-L-arginine (30 microM), inhibited hypoxic relaxations in intact rat aortas, but left those in coronary arteries unchanged. Similar results were obtained with methylene blue and LY 83583. In preparations without endothelium, sodium nitroprusside (30 nM) elicited a reappearance of hypoxic relaxations in the rat but not the dog coronary artery. Thus, hypoxic relaxation is mediated by a prostaglandin in the dog coronary artery, but by endothelium-derived NO in the rat aorta. As the response was dependent on the level of contraction, this suggests that the release or action of NO decreases with increasing tone."} {"id": "PMID:1282945", "title": "Calcium activation of hyperpolarization response to acetylcholine in coronary endothelial cells.", "content": "Hyperpolarization response to acetylcholine (ACh) in endothelial cells was studied by intracellular recording of an intact endothelium preparation of guinea pig coronary artery. The hyperpolarization requires the presence of extracellular Ca2+ and the response was progressively blocked by MnCl2 or by removal of extracellular Ca2+. The intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8, 10 microM), was also effective in abolishing the hyperpolarization. Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca2+ pump, potentiated the hyperpolarization to ACh but inhibited caffeine-induced hyperpolarization. These findings suggest that ACh-induced hyperpolarization is mediated by an increase in cytosolic Ca2+ due to influx of extracellular Ca2+ and release of Ca2+ from an internal IP3-sensitive store. The rise in cytosolic Ca2+ level was modulated by a caffeine-sensitive pool that is inhibited by cyclopiazonic acid.", "contents": "Calcium activation of hyperpolarization response to acetylcholine in coronary endothelial cells. Hyperpolarization response to acetylcholine (ACh) in endothelial cells was studied by intracellular recording of an intact endothelium preparation of guinea pig coronary artery. The hyperpolarization requires the presence of extracellular Ca2+ and the response was progressively blocked by MnCl2 or by removal of extracellular Ca2+. The intracellular Ca2+ antagonist, 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester hydrochloride (TMB-8, 10 microM), was also effective in abolishing the hyperpolarization. Cyclopiazonic acid, an inhibitor of the sarcoplasmic reticulum Ca2+ pump, potentiated the hyperpolarization to ACh but inhibited caffeine-induced hyperpolarization. These findings suggest that ACh-induced hyperpolarization is mediated by an increase in cytosolic Ca2+ due to influx of extracellular Ca2+ and release of Ca2+ from an internal IP3-sensitive store. The rise in cytosolic Ca2+ level was modulated by a caffeine-sensitive pool that is inhibited by cyclopiazonic acid."} {"id": "PMID:1282946", "title": "Endothelial modulation of DNA synthesis in isolated arteries of the rat.", "content": "The endothelium can modulate the supply of growth factors to the underlying smooth muscle. In vitro experiments suggest that it may also influence the responsiveness of arterial smooth muscle to mitogens. In these experiments, we measured DNA synthesis in segments of carotid and renal arteries that were isolated from Wistar-Kyoto (WKY) rats and exposed to serum. Nuclear incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdUrd), was visualized by immunocytochemistry and the percentage of labeled nuclei (BrdUrd L%) was determined in the tunica media. In both types of artery isolated from 6- and 20-week-old WKY rats, mechanical removal of endothelium increased the BrdUrd L% in the tunica media. In carotid arteries of 20-week-old WKY rats, gentle denudation increased the incorporation of [3H]thymidine but not [14C]leucine. In denuded renal arteries of adult WKY rats, exogenous prostaglandin E2, iloprost, and transforming growth factor-beta (TGF-beta) reduced media labeling, which was not affected by Na nitroprusside. In renal arteries with endothelium, methylene blue and indomethacin did not affect medial DNA synthesis. These findings demonstrate that in arteries of young and adult rats, the endothelium reduces stimulated DNA synthesis. It is unlikely that basal production of nitric oxide or prostaglandins is involved herein. Endothelial inhibition of DNA synthesis but not protein synthesis in arteries indicates that the endothelium may influence the extent of arterial smooth muscle hypertrophy and hyperplasia.", "contents": "Endothelial modulation of DNA synthesis in isolated arteries of the rat. The endothelium can modulate the supply of growth factors to the underlying smooth muscle. In vitro experiments suggest that it may also influence the responsiveness of arterial smooth muscle to mitogens. In these experiments, we measured DNA synthesis in segments of carotid and renal arteries that were isolated from Wistar-Kyoto (WKY) rats and exposed to serum. Nuclear incorporation of the thymidine analogue, 5-bromo-2'-deoxyuridine (BrdUrd), was visualized by immunocytochemistry and the percentage of labeled nuclei (BrdUrd L%) was determined in the tunica media. In both types of artery isolated from 6- and 20-week-old WKY rats, mechanical removal of endothelium increased the BrdUrd L% in the tunica media. In carotid arteries of 20-week-old WKY rats, gentle denudation increased the incorporation of [3H]thymidine but not [14C]leucine. In denuded renal arteries of adult WKY rats, exogenous prostaglandin E2, iloprost, and transforming growth factor-beta (TGF-beta) reduced media labeling, which was not affected by Na nitroprusside. In renal arteries with endothelium, methylene blue and indomethacin did not affect medial DNA synthesis. These findings demonstrate that in arteries of young and adult rats, the endothelium reduces stimulated DNA synthesis. It is unlikely that basal production of nitric oxide or prostaglandins is involved herein. Endothelial inhibition of DNA synthesis but not protein synthesis in arteries indicates that the endothelium may influence the extent of arterial smooth muscle hypertrophy and hyperplasia."} {"id": "PMID:1282947", "title": "Vascular smooth muscle proliferation in hypertensive transgenic rats.", "content": "In vascular smooth muscle cell (VSMC) cultures from Sprague-Dawley (SD) and hypertensive transgenic rats for the mouse renin gene Ren-2 (TGR), the DNA synthesis, which was analyzed by the uptake of [3H]thymidine, was higher in TGR than SD VSMCs (2.5- to 8-fold, mean of 5.6-fold) under basal conditions. DNA synthesis was increased by fetal calf serum (10%) in SD cells more than in TGR VSMCs, and was decreased by heparin (400 micrograms/ml) and by phorbol-12,13-dibutyrate (10(-7) M) in TGR VSMCs to a higher degree than in SD cells. Neither endothelin (10(-7) M), angiotensinogen (10(-8) M), the renin inhibitor CGP 29,287 (10(-4) M), angiotensin I (10(-7) M), captopril (10(-5) M), angiotensin II (10(-7) M), nor saralasin (10(-6) M) modified DNA synthesis in either type of VSMCs. Sodium nitroprusside (10(-4) and 10(-3) M) increased DNA synthesis in both kinds of VSMCs but in TGR cultures it became toxic at 10(-3) M. 8-Bromocyclic GMP (10(-7) to 10(-5) M) reduced DNA synthesis in SD cells more than in TGR VSMCs. These results suggest that (a) cellular mechanisms of proliferation appear to be more activated in TGR VSMCs, likely involving a protein kinase C-dependent pathway but not the renin-angiotensin system, and (b) in both type of cells, sodium nitroprusside possesses proliferative properties whereas 8-bromocyclic GMP has antiproliferative properties.", "contents": "Vascular smooth muscle proliferation in hypertensive transgenic rats. In vascular smooth muscle cell (VSMC) cultures from Sprague-Dawley (SD) and hypertensive transgenic rats for the mouse renin gene Ren-2 (TGR), the DNA synthesis, which was analyzed by the uptake of [3H]thymidine, was higher in TGR than SD VSMCs (2.5- to 8-fold, mean of 5.6-fold) under basal conditions. DNA synthesis was increased by fetal calf serum (10%) in SD cells more than in TGR VSMCs, and was decreased by heparin (400 micrograms/ml) and by phorbol-12,13-dibutyrate (10(-7) M) in TGR VSMCs to a higher degree than in SD cells. Neither endothelin (10(-7) M), angiotensinogen (10(-8) M), the renin inhibitor CGP 29,287 (10(-4) M), angiotensin I (10(-7) M), captopril (10(-5) M), angiotensin II (10(-7) M), nor saralasin (10(-6) M) modified DNA synthesis in either type of VSMCs. Sodium nitroprusside (10(-4) and 10(-3) M) increased DNA synthesis in both kinds of VSMCs but in TGR cultures it became toxic at 10(-3) M. 8-Bromocyclic GMP (10(-7) to 10(-5) M) reduced DNA synthesis in SD cells more than in TGR VSMCs. These results suggest that (a) cellular mechanisms of proliferation appear to be more activated in TGR VSMCs, likely involving a protein kinase C-dependent pathway but not the renin-angiotensin system, and (b) in both type of cells, sodium nitroprusside possesses proliferative properties whereas 8-bromocyclic GMP has antiproliferative properties."} {"id": "PMID:1282948", "title": "The role of nitric oxide in endotoxic shock: effects of NG-monomethyl-L-arginine.", "content": "The role of nitric oxide (NO) in the changes in blood pressure and plasma levels of nitrate and nitrite (NOx) and alanine aminotransferase (ALT) were determined over a 5-h period in anesthesized rats after intravenous administration of S. typhosa endotoxin (LPS, 4 mg/kg). Rats treated with LPS showed a sustained fall in blood pressure accompanied by an increase in plasma NOx and ALT. Forty percent of these rats died during the experiment. There was no change in blood pressure in rats treated with dexamethasone (1 mg/kg) 1 h before and 2 h after LPS and the increase in NOx and ALT was significantly inhibited. None of the rats in this group died. Administration of 10 mg/kg of NG-monomethyl-L-arginine (L-NMMA) prevented the fall in blood pressure and partially prevented the increase in NOx and ALT. None of the animals in this group died. In contrast, 300 mg/kg of L-NMMA caused an initial increase in blood pressure followed by a rapid fall and enhanced the increase in ALT while abolishing the elevation of NOx. All of these animals died before the end of the experiment. However, when rats treated with high doses of L-NMMA were given a continuous infusion of S-nitroso-N-acetylpenicillamine (SNAP, 300 micrograms/kg/h), the blood pressure was maintained at control levels and no mortality was observed.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "The role of nitric oxide in endotoxic shock: effects of NG-monomethyl-L-arginine. The role of nitric oxide (NO) in the changes in blood pressure and plasma levels of nitrate and nitrite (NOx) and alanine aminotransferase (ALT) were determined over a 5-h period in anesthesized rats after intravenous administration of S. typhosa endotoxin (LPS, 4 mg/kg). Rats treated with LPS showed a sustained fall in blood pressure accompanied by an increase in plasma NOx and ALT. Forty percent of these rats died during the experiment. There was no change in blood pressure in rats treated with dexamethasone (1 mg/kg) 1 h before and 2 h after LPS and the increase in NOx and ALT was significantly inhibited. None of the rats in this group died. Administration of 10 mg/kg of NG-monomethyl-L-arginine (L-NMMA) prevented the fall in blood pressure and partially prevented the increase in NOx and ALT. None of the animals in this group died. In contrast, 300 mg/kg of L-NMMA caused an initial increase in blood pressure followed by a rapid fall and enhanced the increase in ALT while abolishing the elevation of NOx. All of these animals died before the end of the experiment. However, when rats treated with high doses of L-NMMA were given a continuous infusion of S-nitroso-N-acetylpenicillamine (SNAP, 300 micrograms/kg/h), the blood pressure was maintained at control levels and no mortality was observed.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282949", "title": "Endothelium-derived kinins account for the immediate response of endothelial cells to bacterial lipopolysaccharide.", "content": "We have recently shown that cultured endothelial cells produce kinins that can stimulate endothelial nitric oxide (NO) production in an autocrine manner. Because both the kallikrein-kinin system and the L-arginine/NO pathway have been implicated in the pathogenesis of septic shock, we investigated the possible involvement of endothelium-derived kinins in the response of cultured endothelial cells to bacterial lipopolysaccharide (LPS). In primary cultures of human umbilical vein and porcine aortic endothelial cells, LPS (0.3 to 3 micrograms/ml) induced significant concentration-dependent increases in cyclic GMP and 6-keto-PGF1 alpha, both of which were abolished in the presence of the selective bradykinin B2-receptor antagonist HOE 140 (0.1 microM). These LPS-induced increases in cyclic GMP and 6-keto-PGF1 alpha were short lived, being maximal after 5 min but were not apparent after 60 min. In parallel with these effects, LPS (30 micrograms/ml) induced a distinct, HOE 140-sensitive increase in the intracellular calcium concentration of human endothelial cells loaded with indo-1. In summary, these data suggest that the release of endothelium-derived kinin and subsequent stimulation of endothelial cells, followed by the enhanced production of NO and prostacyclin (PGI2), are implicated in the immediate hypotension induced by LPS in vivo.", "contents": "Endothelium-derived kinins account for the immediate response of endothelial cells to bacterial lipopolysaccharide. We have recently shown that cultured endothelial cells produce kinins that can stimulate endothelial nitric oxide (NO) production in an autocrine manner. Because both the kallikrein-kinin system and the L-arginine/NO pathway have been implicated in the pathogenesis of septic shock, we investigated the possible involvement of endothelium-derived kinins in the response of cultured endothelial cells to bacterial lipopolysaccharide (LPS). In primary cultures of human umbilical vein and porcine aortic endothelial cells, LPS (0.3 to 3 micrograms/ml) induced significant concentration-dependent increases in cyclic GMP and 6-keto-PGF1 alpha, both of which were abolished in the presence of the selective bradykinin B2-receptor antagonist HOE 140 (0.1 microM). These LPS-induced increases in cyclic GMP and 6-keto-PGF1 alpha were short lived, being maximal after 5 min but were not apparent after 60 min. In parallel with these effects, LPS (30 micrograms/ml) induced a distinct, HOE 140-sensitive increase in the intracellular calcium concentration of human endothelial cells loaded with indo-1. In summary, these data suggest that the release of endothelium-derived kinin and subsequent stimulation of endothelial cells, followed by the enhanced production of NO and prostacyclin (PGI2), are implicated in the immediate hypotension induced by LPS in vivo."} {"id": "PMID:1282950", "title": "Characterization of a microsomal calcium-dependent nitric oxide synthase in activated J774.2 monocyte/macrophages.", "content": "The nitric oxide (NO) synthase activity present in murine J774.2 monocyte/macrophages was characterized in terms of its intracellular localization, substrate specificity, and Ca2+ dependency. Traces of constitutive NO synthase activity were found in the microsomal fraction from noninduced J774.2 cells, whereas no NO synthase activity was detected in the cytosol. After 24 h in the presence of bacterial lipopolysaccharide and mouse interferon, NO synthase activity was substantially increased in both fractions with 51-60% of the total activity present in the cytosol. These activities, however, were clearly different, for the microsomal enzyme was Ca2+ dependent, whereas the cytosolic NO synthase was not. Moreover, NG-hydroxy-L-arginine (L-HOArg), L-homo-arginine, and several L-arginine (L-Arg)-containing dipeptides could replace L-Arg as substrates for the Ca(2+)-independent NO synthase, whereas the Ca(2+)-dependent enzyme accepted only L-Arg, L-HOArg, or L-Arg-L-Arg as substrates. Thus, a microsomal Ca(2+)-dependent NO synthase is induced in J774.2 monocyte/macrophages with a substrate specificity different from the inducible Ca(2+)-independent NO synthase as well as the constitutive NO synthase in, for example, endothelial cells. Irrespective of their intracellular localization, therefore, at least three isoforms of NO synthase exist, all of which can accommodate substrates different from L-Arg in size, charge, and hydrophobicity.", "contents": "Characterization of a microsomal calcium-dependent nitric oxide synthase in activated J774.2 monocyte/macrophages. The nitric oxide (NO) synthase activity present in murine J774.2 monocyte/macrophages was characterized in terms of its intracellular localization, substrate specificity, and Ca2+ dependency. Traces of constitutive NO synthase activity were found in the microsomal fraction from noninduced J774.2 cells, whereas no NO synthase activity was detected in the cytosol. After 24 h in the presence of bacterial lipopolysaccharide and mouse interferon, NO synthase activity was substantially increased in both fractions with 51-60% of the total activity present in the cytosol. These activities, however, were clearly different, for the microsomal enzyme was Ca2+ dependent, whereas the cytosolic NO synthase was not. Moreover, NG-hydroxy-L-arginine (L-HOArg), L-homo-arginine, and several L-arginine (L-Arg)-containing dipeptides could replace L-Arg as substrates for the Ca(2+)-independent NO synthase, whereas the Ca(2+)-dependent enzyme accepted only L-Arg, L-HOArg, or L-Arg-L-Arg as substrates. Thus, a microsomal Ca(2+)-dependent NO synthase is induced in J774.2 monocyte/macrophages with a substrate specificity different from the inducible Ca(2+)-independent NO synthase as well as the constitutive NO synthase in, for example, endothelial cells. Irrespective of their intracellular localization, therefore, at least three isoforms of NO synthase exist, all of which can accommodate substrates different from L-Arg in size, charge, and hydrophobicity."} {"id": "PMID:1282951", "title": "The inducible nitric oxide synthase is impaired by thrombin in vascular smooth muscle cells.", "content": "The present study investigated whether or not thrombin may affect the induction of nitric oxide (NO) synthase caused by interleukin-1 beta in cultured smooth muscle cells (SMCs) from the rat aorta. The release of nitrite, an oxidation product of NO, from interleukin-1 beta-activated SMCs was inhibited by thrombin. The inhibitory effect of thrombin was prevented by hirudin, a thrombin inhibitor, and required the presence of thrombin during the induction period. Under bioassay conditions, the perfusate from interleukin-1 beta-activated SMCs relaxed endothelium-denuded rat aortic rings precontracted with phenylephrine. The perfusate from untreated SMCs or cells exposed to thrombin alone or to interleukin-1 beta in combination with thrombin relaxed only minimally the detector blood vessel. These observations demonstrate that thrombin inhibits the production of NO by the inducible NO synthase in cultured vascular SMCs.", "contents": "The inducible nitric oxide synthase is impaired by thrombin in vascular smooth muscle cells. The present study investigated whether or not thrombin may affect the induction of nitric oxide (NO) synthase caused by interleukin-1 beta in cultured smooth muscle cells (SMCs) from the rat aorta. The release of nitrite, an oxidation product of NO, from interleukin-1 beta-activated SMCs was inhibited by thrombin. The inhibitory effect of thrombin was prevented by hirudin, a thrombin inhibitor, and required the presence of thrombin during the induction period. Under bioassay conditions, the perfusate from interleukin-1 beta-activated SMCs relaxed endothelium-denuded rat aortic rings precontracted with phenylephrine. The perfusate from untreated SMCs or cells exposed to thrombin alone or to interleukin-1 beta in combination with thrombin relaxed only minimally the detector blood vessel. These observations demonstrate that thrombin inhibits the production of NO by the inducible NO synthase in cultured vascular SMCs."} {"id": "PMID:1282952", "title": "Lipoteichoic acid: a new inducer of nitric oxide synthase.", "content": "Inducible nitric oxide (NO) synthase in vascular smooth muscle cells (SMCs) appears to play a major role for the diminished responsiveness to vasoconstrictors observed in endotoxemia. However, cardiovascular dysfunctions associated with septic shock are also observed in the absence of endotoxin (LPS). Similar hemodynamic changes are produced either by a gram-negative bacteria (Escherichia coli) or by a gram-positive bacteria (Staphylococcus aureus), a microorganism without LPS, suggesting a common pathway leading to cardiovascular abnormalities. In the present study, we describe the induction of NO synthase in vascular SMCs by lipoteichoic acid (LTA), a component of the membrane of gram-positive bacteria. In cultured vascular SMCs, a 24-h incubation with LTA produced an increase in intracellular cyclic GMP. This effect was inhibited by methylene blue (MB), an inhibitor of guanylate cyclase. Incubation with a specific inhibitor of L-arginine, i.e., NG-nitro-L-arginine methyl ester (L-NAME), or depletion of L-arginine attenuated the LTA-induced cGMP production. A 5-h incubation of endothelium-free rings of rat aorta in the presence of LTA induced a loss of tonicity to the contractile response of phenylephrine. The contractions were restored by MB and by L-NAME. The effect of L-NAME was reversed by L-arginine. These results show that LTA, like LPS, expresses NO synthase in vascular SMCs.", "contents": "Lipoteichoic acid: a new inducer of nitric oxide synthase. Inducible nitric oxide (NO) synthase in vascular smooth muscle cells (SMCs) appears to play a major role for the diminished responsiveness to vasoconstrictors observed in endotoxemia. However, cardiovascular dysfunctions associated with septic shock are also observed in the absence of endotoxin (LPS). Similar hemodynamic changes are produced either by a gram-negative bacteria (Escherichia coli) or by a gram-positive bacteria (Staphylococcus aureus), a microorganism without LPS, suggesting a common pathway leading to cardiovascular abnormalities. In the present study, we describe the induction of NO synthase in vascular SMCs by lipoteichoic acid (LTA), a component of the membrane of gram-positive bacteria. In cultured vascular SMCs, a 24-h incubation with LTA produced an increase in intracellular cyclic GMP. This effect was inhibited by methylene blue (MB), an inhibitor of guanylate cyclase. Incubation with a specific inhibitor of L-arginine, i.e., NG-nitro-L-arginine methyl ester (L-NAME), or depletion of L-arginine attenuated the LTA-induced cGMP production. A 5-h incubation of endothelium-free rings of rat aorta in the presence of LTA induced a loss of tonicity to the contractile response of phenylephrine. The contractions were restored by MB and by L-NAME. The effect of L-NAME was reversed by L-arginine. These results show that LTA, like LPS, expresses NO synthase in vascular SMCs."} {"id": "PMID:1282953", "title": "Exogenous nitric oxide stress on endothelial cells and macrophages.", "content": "Bovine endothelial cells (ECs, P1) and lipopolysaccharide/gamma-interferon-induced mouse macrophages (MMs) were incubated in the presence of SIN-1 and C 3754 (1 microM to 1 mM), sydnonimine metabolites of the antianginal predrugs molsidomine and pirsidomine, respectively up to 48 h. No change of the endogenous nitric oxide output from MMs and A23187- or adenosine triphosphate-stimulated ECs was found by means of the methemoglobin method. Data indicate that downregulation of the nitric oxide (NO) synthase is not obvious within the intact cells under exogenous NO stress supplied by high concentrations of the spontaneous NO donors. Cytosolic MM NO synthase extracts, however, revealed reduction in the enzymic [3H]arginine turnover to [3H]citrulline by SIN-1, but not by C 3786, the pharmacologically active metabolite of pirsidomine.", "contents": "Exogenous nitric oxide stress on endothelial cells and macrophages. Bovine endothelial cells (ECs, P1) and lipopolysaccharide/gamma-interferon-induced mouse macrophages (MMs) were incubated in the presence of SIN-1 and C 3754 (1 microM to 1 mM), sydnonimine metabolites of the antianginal predrugs molsidomine and pirsidomine, respectively up to 48 h. No change of the endogenous nitric oxide output from MMs and A23187- or adenosine triphosphate-stimulated ECs was found by means of the methemoglobin method. Data indicate that downregulation of the nitric oxide (NO) synthase is not obvious within the intact cells under exogenous NO stress supplied by high concentrations of the spontaneous NO donors. Cytosolic MM NO synthase extracts, however, revealed reduction in the enzymic [3H]arginine turnover to [3H]citrulline by SIN-1, but not by C 3786, the pharmacologically active metabolite of pirsidomine."} {"id": "PMID:1282954", "title": "Modulation of arterial endothelin-1 receptors following chronic increases in blood flow.", "content": "Experiments were designed to determine whether or not increased contractions to endothelin-1 (ET-1) in arteries chronically exposed to increased blood flow were due to a change in the subtype, number, or affinity of ET receptors on the smooth muscle. A fistula was created between one femoral artery and vein in dogs; contralateral blood vessels were operated as shams. After 6 weeks, the femoral arteries were removed. In both fistula- and sham-operated arteries suspended for the measurement of isometric force in organ chambers, the contractile potency was ET-1 > ET-2 > ET-3. Specific binding of [125I]ET-1 as a function of membrane protein was significantly greater in fistula compared to sham-operated arteries (Bmax = 184.8 +/- 35.9 and 117.4 +/- 25.6 fmol/mg, n = 6, respectively). Affinity of binding was the same in each group of arteries. These results suggest that ETA receptors mediate contraction on canine femoral arterial smooth muscle. These receptors may be upregulated when the artery is exposed chronically to increased blood flow.", "contents": "Modulation of arterial endothelin-1 receptors following chronic increases in blood flow. Experiments were designed to determine whether or not increased contractions to endothelin-1 (ET-1) in arteries chronically exposed to increased blood flow were due to a change in the subtype, number, or affinity of ET receptors on the smooth muscle. A fistula was created between one femoral artery and vein in dogs; contralateral blood vessels were operated as shams. After 6 weeks, the femoral arteries were removed. In both fistula- and sham-operated arteries suspended for the measurement of isometric force in organ chambers, the contractile potency was ET-1 > ET-2 > ET-3. Specific binding of [125I]ET-1 as a function of membrane protein was significantly greater in fistula compared to sham-operated arteries (Bmax = 184.8 +/- 35.9 and 117.4 +/- 25.6 fmol/mg, n = 6, respectively). Affinity of binding was the same in each group of arteries. These results suggest that ETA receptors mediate contraction on canine femoral arterial smooth muscle. These receptors may be upregulated when the artery is exposed chronically to increased blood flow."} {"id": "PMID:1282955", "title": "Balloon injury induces nitric oxide synthase activity in rat carotid arteries.", "content": "Experiments were performed to investigate whether or not balloon injury induces nitric oxide (NO) synthase activity in the arterial wall removed. Contractions to phenylephrine were compared in left carotid arteries of the rat, previously injured by balloon catheterization and collected 24 h after the procedure, and in control right carotid arteries in which the endothelium was removed acutely. Phenylephrine evoked concentration-dependent contractions in balloon-injured and control carotid arteries without endothelium. However, in the balloon-injured carotid arteries, the concentration-contraction curves to phenylephrine were shifted significantly to the right compared to those observed in control carotid arteries without endothelium. In balloon-injured arteries, nitro-L-arginine restored full contractions, whereas superoxide dismutase potentiated the hyporesponsiveness to phenylephrine. The depressed contractions were associated with a concomitant increase in the basal level of guanosine-3',5'-cyclic monophosphate; this production was abolished by nitro-L-arginine. These observations indicate that in vivo endothelial injury of the rat carotid arteries induces the production of nitric oxide from L-arginine in the arterial wall.", "contents": "Balloon injury induces nitric oxide synthase activity in rat carotid arteries. Experiments were performed to investigate whether or not balloon injury induces nitric oxide (NO) synthase activity in the arterial wall removed. Contractions to phenylephrine were compared in left carotid arteries of the rat, previously injured by balloon catheterization and collected 24 h after the procedure, and in control right carotid arteries in which the endothelium was removed acutely. Phenylephrine evoked concentration-dependent contractions in balloon-injured and control carotid arteries without endothelium. However, in the balloon-injured carotid arteries, the concentration-contraction curves to phenylephrine were shifted significantly to the right compared to those observed in control carotid arteries without endothelium. In balloon-injured arteries, nitro-L-arginine restored full contractions, whereas superoxide dismutase potentiated the hyporesponsiveness to phenylephrine. The depressed contractions were associated with a concomitant increase in the basal level of guanosine-3',5'-cyclic monophosphate; this production was abolished by nitro-L-arginine. These observations indicate that in vivo endothelial injury of the rat carotid arteries induces the production of nitric oxide from L-arginine in the arterial wall."} {"id": "PMID:1282956", "title": "Involvement of nitric oxide in tumor cell adhesion to cytokine-activated endothelial cells.", "content": "The aim of the present experiments was to test the possible involvement of nitric oxide (NO) in cytokine-induced enhancement of tumor cell (TC) adhesion to endothelial cells (ECs). Exposure of EA hyb 926 cells to TNF (500 U/ml) plus IFN (100 U/ml) for 24 h significantly enhanced their adhesivity for the 51Cr-labeled GLC1 (small cell lung carcinoma) TCs. Conversely, exposure of TCs to cytokines did not result in an increased adhesion of these cells to ECs. TC-stimulated adhesion to EA hyb 926 was abrogated by the glucocorticoid dexamethasone (Dex, 10(-7) M), the NO synthase inhibitors N omega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) and NG-monomethyl-L-arginine (L-NMMA, 10(-5) M) and the protein synthesis inhibitor cycloheximide (Cex, 10(-6) M). Furthermore, GLC1-stimulated adhesion to EA hyb 926 was reversed following removal of L-arginine from the medium or pretreatment with the guanylate cyclase inhibitor methylene blue. TC-stimulated adhesion was also prevented when TCs were pretreated with the monoclonal antibody CD15 directed against the endothelial-leukocyte adhesion molecule (ELAM-1) ligand or following exposure of ECs to anti-ELAM-1 monoclonal antibody. Although suppressing TC-stimulated adhesion, L-NMMA failed to modify significantly cytokine-induced ELAM-1 expression in EA hyb 926. These results (a) provide evidence for the NO-inducible pathway contributing to cytokine-induced enhancement of tumor cell adhesion to the vascular endothelium and (b) demonstrate the involvement of the ELAM-1/CD15 adhesion system in tumor cell-stimulated adhesion to ECs.", "contents": "Involvement of nitric oxide in tumor cell adhesion to cytokine-activated endothelial cells. The aim of the present experiments was to test the possible involvement of nitric oxide (NO) in cytokine-induced enhancement of tumor cell (TC) adhesion to endothelial cells (ECs). Exposure of EA hyb 926 cells to TNF (500 U/ml) plus IFN (100 U/ml) for 24 h significantly enhanced their adhesivity for the 51Cr-labeled GLC1 (small cell lung carcinoma) TCs. Conversely, exposure of TCs to cytokines did not result in an increased adhesion of these cells to ECs. TC-stimulated adhesion to EA hyb 926 was abrogated by the glucocorticoid dexamethasone (Dex, 10(-7) M), the NO synthase inhibitors N omega-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) and NG-monomethyl-L-arginine (L-NMMA, 10(-5) M) and the protein synthesis inhibitor cycloheximide (Cex, 10(-6) M). Furthermore, GLC1-stimulated adhesion to EA hyb 926 was reversed following removal of L-arginine from the medium or pretreatment with the guanylate cyclase inhibitor methylene blue. TC-stimulated adhesion was also prevented when TCs were pretreated with the monoclonal antibody CD15 directed against the endothelial-leukocyte adhesion molecule (ELAM-1) ligand or following exposure of ECs to anti-ELAM-1 monoclonal antibody. Although suppressing TC-stimulated adhesion, L-NMMA failed to modify significantly cytokine-induced ELAM-1 expression in EA hyb 926. These results (a) provide evidence for the NO-inducible pathway contributing to cytokine-induced enhancement of tumor cell adhesion to the vascular endothelium and (b) demonstrate the involvement of the ELAM-1/CD15 adhesion system in tumor cell-stimulated adhesion to ECs."} {"id": "PMID:1282957", "title": "Control of renal hemodynamics during intrarenal and systemic blockade of nitric oxide synthesis in conscious dogs.", "content": "Systemic blockade of nitric oxide (NO) synthesis results in marked increases in the renal vascular resistance (RVR) and decreases in the glomerular filtration rate (GFR) and renal plasma flow (RPF). The renal hemodynamic effect of systemic NO blockade is most likely due to an integration of direct and indirect renal actions. The quantitative importance of local intrarenal blockade of NO synthesis on renal hemodynamics has not been fully elucidated. Therefore, the purpose of this study was to compare the renal hemodynamic effects of intrarenal vs. systemic NO synthesis blockade on renal hemodynamics. Nitro-L-arginine methyl ester (L-NAME) was infused intrarenally at a rate of 3 micrograms/kg/min for 180 min in conscious chronically instrumented dogs (n = 7). Intrarenal infusion of L-NAME for 180 min resulted in a 12% decrease in RPF, 14% increase in RVR, and no effect on mean arterial pressure (MAP) or GFR. In contrast, infusion of L-NAME intravenously at a rate of 10 micrograms/kg/min for 180 min increased the RVR by 124% and decreased the RPF by 55% and GFR by 45%. The MAP and heart rate both increased in response to intravenous administration of L-NAME. The results of this study suggest that the renal hemodynamic effects of systemic administration of L-NAME may, in large part, be secondary to extrarenal effects of NO synthesis blockade, possibly via activation of the sympathetic nervous system.", "contents": "Control of renal hemodynamics during intrarenal and systemic blockade of nitric oxide synthesis in conscious dogs. Systemic blockade of nitric oxide (NO) synthesis results in marked increases in the renal vascular resistance (RVR) and decreases in the glomerular filtration rate (GFR) and renal plasma flow (RPF). The renal hemodynamic effect of systemic NO blockade is most likely due to an integration of direct and indirect renal actions. The quantitative importance of local intrarenal blockade of NO synthesis on renal hemodynamics has not been fully elucidated. Therefore, the purpose of this study was to compare the renal hemodynamic effects of intrarenal vs. systemic NO synthesis blockade on renal hemodynamics. Nitro-L-arginine methyl ester (L-NAME) was infused intrarenally at a rate of 3 micrograms/kg/min for 180 min in conscious chronically instrumented dogs (n = 7). Intrarenal infusion of L-NAME for 180 min resulted in a 12% decrease in RPF, 14% increase in RVR, and no effect on mean arterial pressure (MAP) or GFR. In contrast, infusion of L-NAME intravenously at a rate of 10 micrograms/kg/min for 180 min increased the RVR by 124% and decreased the RPF by 55% and GFR by 45%. The MAP and heart rate both increased in response to intravenous administration of L-NAME. The results of this study suggest that the renal hemodynamic effects of systemic administration of L-NAME may, in large part, be secondary to extrarenal effects of NO synthesis blockade, possibly via activation of the sympathetic nervous system."} {"id": "PMID:1282958", "title": "Endothelium-derived relaxing factor modulates renal interstitial cyclic GMP.", "content": "The arterial vasodilator activity of endothelium-derived relaxing factor (EDRF) is mediated by activation of the soluble form of guanylate cyclase, causing increased levels of guanosine-3',5'-cyclic monophosphate (cGMP). Because of its extreme lability, the actions of EDRF are local. The ability to monitor changes in renal interstitial fluid cGMP would be of great advantage in clarification of local mechanisms controlling renal function. Utilizing a renal interstitial microdialysis technique, we investigated changes in renal interstitial and urinary cGMP in response to right intrarenal arterial administration of the EDRF inhibitor, NG-monomethyl-L-arginine (L-NMMA), in anesthetized dogs (n = 5) in metabolic balance at a sodium intake of 40 mEq/day. Urine was collected directly from the right and left ureter. L-NMMA at 20-60 micrograms/kg/min significantly decreased right renal interstitial and right urinary cGMP levels (p < 0.01) without changing left renal interstitial and urinary cGMP levels (p < 0.01). L-NMMA at 100 micrograms/kg/min decreased both right and left renal interstitial and urinary cGMP levels (p < 0.01). These data demonstrate the ability to monitor renal interstitial cGMP in vivo. There was a dose-dependent decrease in renal interstitial and urinary cGMP in response to intrarenal EDRF inhibition. Additionally, they suggest that EDRF acts as a renal paracrine substance through the modulation of renal interstitial cGMP.", "contents": "Endothelium-derived relaxing factor modulates renal interstitial cyclic GMP. The arterial vasodilator activity of endothelium-derived relaxing factor (EDRF) is mediated by activation of the soluble form of guanylate cyclase, causing increased levels of guanosine-3',5'-cyclic monophosphate (cGMP). Because of its extreme lability, the actions of EDRF are local. The ability to monitor changes in renal interstitial fluid cGMP would be of great advantage in clarification of local mechanisms controlling renal function. Utilizing a renal interstitial microdialysis technique, we investigated changes in renal interstitial and urinary cGMP in response to right intrarenal arterial administration of the EDRF inhibitor, NG-monomethyl-L-arginine (L-NMMA), in anesthetized dogs (n = 5) in metabolic balance at a sodium intake of 40 mEq/day. Urine was collected directly from the right and left ureter. L-NMMA at 20-60 micrograms/kg/min significantly decreased right renal interstitial and right urinary cGMP levels (p < 0.01) without changing left renal interstitial and urinary cGMP levels (p < 0.01). L-NMMA at 100 micrograms/kg/min decreased both right and left renal interstitial and urinary cGMP levels (p < 0.01). These data demonstrate the ability to monitor renal interstitial cGMP in vivo. There was a dose-dependent decrease in renal interstitial and urinary cGMP in response to intrarenal EDRF inhibition. Additionally, they suggest that EDRF acts as a renal paracrine substance through the modulation of renal interstitial cGMP."} {"id": "PMID:1282959", "title": "Collateral perfusion: the role of endothelium-derived relaxing factor and effects of vasodilators.", "content": "An in vitro rabbit ear model has been used to investigate the role of endothelium-derived relaxing factor (EDRF) in collateral perfusion after acute arterial occlusion and also the effects of vasodilators. Collateral perfusion of an arterial segment isolated between occlusions was assessed by x-ray microangiography and was found to develop in a time-dependent manner. Inhibition of EDRF synthesis with NG-nitro-L-arginine methyl ester (L-NAME) greatly impaired collateral perfusion, indicating that the development of collateral perfusion was dependent on EDRF activity. This inhibitory effect was reversed by an excess of L-arginine. Further studies using vasodilators with different modes of action indicated that BRL 38227 (the active enantiomer of cromakalim, a potassium channel activator) substantially enhanced collateral perfusion, sodium nitroprusside had early beneficial effects, and verapamil had no effect.", "contents": "Collateral perfusion: the role of endothelium-derived relaxing factor and effects of vasodilators. An in vitro rabbit ear model has been used to investigate the role of endothelium-derived relaxing factor (EDRF) in collateral perfusion after acute arterial occlusion and also the effects of vasodilators. Collateral perfusion of an arterial segment isolated between occlusions was assessed by x-ray microangiography and was found to develop in a time-dependent manner. Inhibition of EDRF synthesis with NG-nitro-L-arginine methyl ester (L-NAME) greatly impaired collateral perfusion, indicating that the development of collateral perfusion was dependent on EDRF activity. This inhibitory effect was reversed by an excess of L-arginine. Further studies using vasodilators with different modes of action indicated that BRL 38227 (the active enantiomer of cromakalim, a potassium channel activator) substantially enhanced collateral perfusion, sodium nitroprusside had early beneficial effects, and verapamil had no effect."} {"id": "PMID:1282960", "title": "Functional hyperemia of skeletal muscle: role of endothelium.", "content": "The role of the endothelium and endothelium-derived vasoactive factors in the development of skeletal muscle functional hyperemia was studied. Experiments were performed in anesthetized dogs. Functional hyperemia of isometrically contracted gastrocnemius muscle was produced by direct electric stimulation. Five series of experiments were conducted to investigate the effect of (a) de-endothelialization of gastrocnemius vessels, (b) inhibition of prostanoids biosynthesis by indomethacin, (c) inhibition by gossipol of lipoxygenase, which mediates biosynthesis of endothelium-derived relaxing factor (EDRF), (d) inhibition of cGMP formation by methylene blue, and (e) stimulation of EDRF biosynthesis of L-arginine. The gastrocnemius muscle work was accompanied by an increase in blood flow by 6.8 +/- 0.6 ml/min/N (8 Hz) and by 2.5 +/- 0.2 ml/min/N) (40 Hz). Chemical deendothelialization of gastrocnemius vessels decreased functional hyperemia, and blood flow increased by only 1.2 +/- 0.3 ml/min/N (8 Hz) and by 0.5 +/- 0.1 ml/min/N (40 Hz). Cyclooxygenase inhibition by indomethacin had no significant effect on functional hyperemia, whereas methylene blue and gossipol inhibited functional hyperemia by 4.2- and 6.6-fold, respectively, and L-arginine significantly elevated blood flow by 12.6 +/- 1.4 ml/min/N (8 Hz) and by 3.5 +/- 0.2 ml/min/N (40 Hz) during skeletal muscle work. Thus, it can be concluded that the endothelium plays an important role in functional hyperemia of skeletal muscle, probably through the release of EDRF.", "contents": "Functional hyperemia of skeletal muscle: role of endothelium. The role of the endothelium and endothelium-derived vasoactive factors in the development of skeletal muscle functional hyperemia was studied. Experiments were performed in anesthetized dogs. Functional hyperemia of isometrically contracted gastrocnemius muscle was produced by direct electric stimulation. Five series of experiments were conducted to investigate the effect of (a) de-endothelialization of gastrocnemius vessels, (b) inhibition of prostanoids biosynthesis by indomethacin, (c) inhibition by gossipol of lipoxygenase, which mediates biosynthesis of endothelium-derived relaxing factor (EDRF), (d) inhibition of cGMP formation by methylene blue, and (e) stimulation of EDRF biosynthesis of L-arginine. The gastrocnemius muscle work was accompanied by an increase in blood flow by 6.8 +/- 0.6 ml/min/N (8 Hz) and by 2.5 +/- 0.2 ml/min/N) (40 Hz). Chemical deendothelialization of gastrocnemius vessels decreased functional hyperemia, and blood flow increased by only 1.2 +/- 0.3 ml/min/N (8 Hz) and by 0.5 +/- 0.1 ml/min/N (40 Hz). Cyclooxygenase inhibition by indomethacin had no significant effect on functional hyperemia, whereas methylene blue and gossipol inhibited functional hyperemia by 4.2- and 6.6-fold, respectively, and L-arginine significantly elevated blood flow by 12.6 +/- 1.4 ml/min/N (8 Hz) and by 3.5 +/- 0.2 ml/min/N (40 Hz) during skeletal muscle work. Thus, it can be concluded that the endothelium plays an important role in functional hyperemia of skeletal muscle, probably through the release of EDRF."} {"id": "PMID:1282961", "title": "Effects of endothelin-1 and inhibition of nitric oxide production with NG-monomethyl-L-arginine on arterial pressure and regional blood flow in anesthetized rats.", "content": "Regional hemodynamic responses to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, were compared with those to endothelin (ET) using tracer microspheres with a reference sample method in anesthetized rats. Intravenous injections of these agents (16 and 160 mmol/kg of L-NMMA and 0.1 or 0.5 nmol/kg of ET-1) dose-dependently increased the blood pressure to the similar level. The cardiac index markedly decreased with ET-1, but was not greatly influenced by L-NMMA. Coronary and cerebral blood flow were not affected by these agents. ET-1 increased the bronchial arterial flow, and markedly decreased the flow in the other organs and tissues examined. L-NMMA almost homogeneously increased the regional vascular resistance to the lesser extent compared to ET-1. Although both ET-1 and nitric oxide are produced in the same cells and exhibit interrelationships, the present results indicate that the regional vascular effects of these agents are different: (a) ET-1 preferentially constricts arteries in all organs and tissues except the lung (where it increases flow) and the heart and brain where it has no wasted effects, leading to reduction in cardiac output, and (b) nitric oxide dilates arteries predominantly in the kidneys, muscle, and white adipose tissues.", "contents": "Effects of endothelin-1 and inhibition of nitric oxide production with NG-monomethyl-L-arginine on arterial pressure and regional blood flow in anesthetized rats. Regional hemodynamic responses to NG-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide synthase, were compared with those to endothelin (ET) using tracer microspheres with a reference sample method in anesthetized rats. Intravenous injections of these agents (16 and 160 mmol/kg of L-NMMA and 0.1 or 0.5 nmol/kg of ET-1) dose-dependently increased the blood pressure to the similar level. The cardiac index markedly decreased with ET-1, but was not greatly influenced by L-NMMA. Coronary and cerebral blood flow were not affected by these agents. ET-1 increased the bronchial arterial flow, and markedly decreased the flow in the other organs and tissues examined. L-NMMA almost homogeneously increased the regional vascular resistance to the lesser extent compared to ET-1. Although both ET-1 and nitric oxide are produced in the same cells and exhibit interrelationships, the present results indicate that the regional vascular effects of these agents are different: (a) ET-1 preferentially constricts arteries in all organs and tissues except the lung (where it increases flow) and the heart and brain where it has no wasted effects, leading to reduction in cardiac output, and (b) nitric oxide dilates arteries predominantly in the kidneys, muscle, and white adipose tissues."} {"id": "PMID:1282962", "title": "Role of endocardial endothelium in the positive inotropic effect of cholic acid in isolated myocardium.", "content": "In isolated feline right ventricular papillary muscles, with intact or damaged (exposure to dry air for 30 s) endocardium, the effects of cholic acid were studied. At 35 degrees C and a [Ca2+] of 1.25 mM, isometric twitches and the maximal unloaded velocity of shortening (Vmax) were registered. Endocardial endothelium (EE) and myocardial ultrastructure were evaluated on scanning and transmission electron microscopy. In muscles with intact EE, low concentrations of cholic acid (3 x 10(-9) to 3 x 10(-7) M) or short incubation (30 min) with 3 x 10(-8) M induced a mild positive inotropic response, manifested as an increased peak isometric twitch tension (TT) and shortened twitch duration, without changes in Vmax. This inotropic response was abolished by damaging the EE. It was also absent after the addition of propranolol to muscles with intact EE. Higher concentrations (3 x 10(-6) to 3 x 10(-4) M) or prolonged incubation at 3 x 10(-8) M caused extensive morphologic damage of the EE, without detectable impairment of subjacent myocardium. This was accompanied by a progressive decrease in the TT and further twitch abbreviation, without changes in Vmax, resembling twitches obtained from muscles with experimentally damaged EE. These observations suggest that cholic acid induces an EE-dependent and beta-receptor-mediated positive inotropic effect, while simultaneously causing damage to EE cells.", "contents": "Role of endocardial endothelium in the positive inotropic effect of cholic acid in isolated myocardium. In isolated feline right ventricular papillary muscles, with intact or damaged (exposure to dry air for 30 s) endocardium, the effects of cholic acid were studied. At 35 degrees C and a [Ca2+] of 1.25 mM, isometric twitches and the maximal unloaded velocity of shortening (Vmax) were registered. Endocardial endothelium (EE) and myocardial ultrastructure were evaluated on scanning and transmission electron microscopy. In muscles with intact EE, low concentrations of cholic acid (3 x 10(-9) to 3 x 10(-7) M) or short incubation (30 min) with 3 x 10(-8) M induced a mild positive inotropic response, manifested as an increased peak isometric twitch tension (TT) and shortened twitch duration, without changes in Vmax. This inotropic response was abolished by damaging the EE. It was also absent after the addition of propranolol to muscles with intact EE. Higher concentrations (3 x 10(-6) to 3 x 10(-4) M) or prolonged incubation at 3 x 10(-8) M caused extensive morphologic damage of the EE, without detectable impairment of subjacent myocardium. This was accompanied by a progressive decrease in the TT and further twitch abbreviation, without changes in Vmax, resembling twitches obtained from muscles with experimentally damaged EE. These observations suggest that cholic acid induces an EE-dependent and beta-receptor-mediated positive inotropic effect, while simultaneously causing damage to EE cells."} {"id": "PMID:1282963", "title": "The role of nitric oxide in the regulation of coronary vascular resistance in arterial hypertension: comparison of normotensive and spontaneously hypertensive rats.", "content": "Nitric oxide (NO) plays an important role in the regulation of coronary vascular resistance. The aim of the present study was to evaluate the role of NO in the regulation of coronary vascular resistance in isolated hearts from normo- and hypertensive rats, which served as a model for arterial hypertension and hypertensive heart disease. Isolated hearts from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were perfused at constant flow, whereas the release of NO into the coronary circulation was measured simultaneously by the oxyhemoglobin technique. Bradykinin, an endothelium-dependent vasodilator, concentration-dependently decreased the coronary perfusion pressure in SHRs by 47 +/- 3% and in WKY rats by 35 +/- 6%. In parallel, the basal NO release increased in both groups, maximally by 154 and 118 pmol/min in SHRs and WKY rats, respectively. Amounts of released NO were sufficient to account for the bradykinin-induced coronary vasodilation. These data indicate that coronary resistance vessels in hearts from hypertensive compared to normotensive rats exhibit a higher sensitivity to the endothelium-dependent vasodilator bradykinin, paralleled by a higher release of NO into the coronary circulation. An enhanced endothelial NO synthesis within the coronary circulation may represent a compensatory mechanism aimed at counterregulating distinct changes in vascular reactivity occurring in arterial hypertension.", "contents": "The role of nitric oxide in the regulation of coronary vascular resistance in arterial hypertension: comparison of normotensive and spontaneously hypertensive rats. Nitric oxide (NO) plays an important role in the regulation of coronary vascular resistance. The aim of the present study was to evaluate the role of NO in the regulation of coronary vascular resistance in isolated hearts from normo- and hypertensive rats, which served as a model for arterial hypertension and hypertensive heart disease. Isolated hearts from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) were perfused at constant flow, whereas the release of NO into the coronary circulation was measured simultaneously by the oxyhemoglobin technique. Bradykinin, an endothelium-dependent vasodilator, concentration-dependently decreased the coronary perfusion pressure in SHRs by 47 +/- 3% and in WKY rats by 35 +/- 6%. In parallel, the basal NO release increased in both groups, maximally by 154 and 118 pmol/min in SHRs and WKY rats, respectively. Amounts of released NO were sufficient to account for the bradykinin-induced coronary vasodilation. These data indicate that coronary resistance vessels in hearts from hypertensive compared to normotensive rats exhibit a higher sensitivity to the endothelium-dependent vasodilator bradykinin, paralleled by a higher release of NO into the coronary circulation. An enhanced endothelial NO synthesis within the coronary circulation may represent a compensatory mechanism aimed at counterregulating distinct changes in vascular reactivity occurring in arterial hypertension."} {"id": "PMID:1282964", "title": "Impaired response to acetylcholine despite intact endothelium-derived relaxing factor/nitric oxide in isolated microperfused afferent arterioles of the spontaneously hypertensive rat.", "content": "The major characteristic of renal hemodynamics in hypertension is abnormally high resistance of the preglomerular vessel, most likely the afferent arteriole (Af-Art). Although endothelium-derived relaxing factor (EDRF)/nitric oxide (NO) has been studied extensively in large vessels, little is known about its role in Af-Art reactivity. Using isolated microperfused Af-Arts of 12- to 13-week-old spontaneously hypertensive rats (SHRs) and their normotensive control, Wistar-Kyoto (WKY) rats, we examined the effect of acetylcholine (ACh) or N omega-nitro-L-arginine (L-NAME), which stimulates or blocks endothelium-derived NO, respectively. Af-Arts were preconstricted with norepinephrine to 70 +/- 5 and 62 +/- 4% of the control diameter in SHRs and WKY rats, respectively; the intraluminal pressure was kept at either 100 or 70 mm Hg. In SHRs, ACh (1 nM-0.1 mM) added to the Af-Art perfusate caused no vasodilation but tended to decrease the diameter further to 59 +/- 6% of control (N = 8). In contrast, in WKY rats, ACh reversed the luminal diameter to 90 +/- 4% of control (N = 6, p < 0.01 compared with SHRs). Contrary to the responses to ACh, blockade of endothelium-derived NO with L-NAME decreased the basal diameter by 31 +/- 8 and 14 +/- 5% in SHRs and WKY rats, respectively. We conclude that ACh-induced vasodilation is impaired in SHR Af-Art. The impaired response to ACh may be due to factors other than endothelium-derived NO such as endothelium-derived contracting factor (EDCF).", "contents": "Impaired response to acetylcholine despite intact endothelium-derived relaxing factor/nitric oxide in isolated microperfused afferent arterioles of the spontaneously hypertensive rat. The major characteristic of renal hemodynamics in hypertension is abnormally high resistance of the preglomerular vessel, most likely the afferent arteriole (Af-Art). Although endothelium-derived relaxing factor (EDRF)/nitric oxide (NO) has been studied extensively in large vessels, little is known about its role in Af-Art reactivity. Using isolated microperfused Af-Arts of 12- to 13-week-old spontaneously hypertensive rats (SHRs) and their normotensive control, Wistar-Kyoto (WKY) rats, we examined the effect of acetylcholine (ACh) or N omega-nitro-L-arginine (L-NAME), which stimulates or blocks endothelium-derived NO, respectively. Af-Arts were preconstricted with norepinephrine to 70 +/- 5 and 62 +/- 4% of the control diameter in SHRs and WKY rats, respectively; the intraluminal pressure was kept at either 100 or 70 mm Hg. In SHRs, ACh (1 nM-0.1 mM) added to the Af-Art perfusate caused no vasodilation but tended to decrease the diameter further to 59 +/- 6% of control (N = 8). In contrast, in WKY rats, ACh reversed the luminal diameter to 90 +/- 4% of control (N = 6, p < 0.01 compared with SHRs). Contrary to the responses to ACh, blockade of endothelium-derived NO with L-NAME decreased the basal diameter by 31 +/- 8 and 14 +/- 5% in SHRs and WKY rats, respectively. We conclude that ACh-induced vasodilation is impaired in SHR Af-Art. The impaired response to ACh may be due to factors other than endothelium-derived NO such as endothelium-derived contracting factor (EDCF)."} {"id": "PMID:1282965", "title": "Detection by bioassay and specific enzyme-linked immunosorbent assay of phosphoramidon-inhibitable endothelin-converting activity in brain and endothelium.", "content": "The endothelin-converting enzyme (ECE) activity present in endothelial cells and rat and human brains was characterized using a selective and rapid bioassay for endothelin-1 (ET-1) or endothelin-3 (ET-3) together with a sensitive enzyme-linked immunosorbent assay. We found that ECE activity was predominantly in the membrane fraction of endothelial cells from which it could be extracted by treatment with detergent. In rat brain tissue, the ECE activity was in the membrane fraction and was not solubilized by detergent treatment. Further dissection of the brain revealed that there was a strong localization of ECE activity in the hypothalamus, midbrain, and medulla oblongata in agreement with earlier observations of ET-like immunoreactivity and binding sites. Experiments with human brain tissue also showed the presence of ECE activity. In conclusion, our studies confirmed the presence of ECE activity within endothelial cells, and showed ECE to be localized in brain tissue in sites consistent with the selective distribution of the ET-1 synthetic pathway. In all tissues studied, the ECE activity was significantly inhibited by phosphoramidon or ethylenediaminetetra-acetate.", "contents": "Detection by bioassay and specific enzyme-linked immunosorbent assay of phosphoramidon-inhibitable endothelin-converting activity in brain and endothelium. The endothelin-converting enzyme (ECE) activity present in endothelial cells and rat and human brains was characterized using a selective and rapid bioassay for endothelin-1 (ET-1) or endothelin-3 (ET-3) together with a sensitive enzyme-linked immunosorbent assay. We found that ECE activity was predominantly in the membrane fraction of endothelial cells from which it could be extracted by treatment with detergent. In rat brain tissue, the ECE activity was in the membrane fraction and was not solubilized by detergent treatment. Further dissection of the brain revealed that there was a strong localization of ECE activity in the hypothalamus, midbrain, and medulla oblongata in agreement with earlier observations of ET-like immunoreactivity and binding sites. Experiments with human brain tissue also showed the presence of ECE activity. In conclusion, our studies confirmed the presence of ECE activity within endothelial cells, and showed ECE to be localized in brain tissue in sites consistent with the selective distribution of the ET-1 synthetic pathway. In all tissues studied, the ECE activity was significantly inhibited by phosphoramidon or ethylenediaminetetra-acetate."} {"id": "PMID:1282966", "title": "Endothelial dysfunction of resistance arteries of spontaneously hypertensive rats.", "content": "Vascular relaxations are impaired in adult spontaneously hypertensive rats (SHRs) because of increased production of endothelium-derived, cyclooxygenase-dependent contractile factors. The objectives of the present study were to determine whether alterations in endothelial function precede the development of hypertension in SHRs and to characterize the contractile factor(s) produced by SHR endothelial cells. Mean systolic blood pressures were minimally (6 mm Hg) higher at 4 weeks of age in SHRs than in Wistar-Kyoto (WKY) rats. Endothelium-mediated relaxations of mesenteric and renal resistance arteries from SHRs and WKY rats were compared in myographs and arteriographs in paired experiments. Acetylcholine (ACh, 10(-9) to 10(-7) M) induced endothelium-dependent relaxations in precontracted mesenteric and renal resistance arteries that were similar in SHRs and WKY rats. At higher concentrations of ACh (10(-6) to 10(-5) M), relaxations were replaced by contractile responses in SHR but not in WKY rat resistance arteries. The contractile responses were endothelium dependent and were inhibited by indomethacin in both mesenteric and renal arteries. Thus, endothelial dysfunction precedes and may contribute to the development of accelerated hypertension in SHRs. SQ 29548, a prostaglandin H2 (PGH2)-thromboxane A2 receptor antagonist, blocked the contractile responses in renal but not in mesenteric resistance arteries. The contractile responses in mesenteric arteries were inhibited by 3-amino-1,2,4-triazole (10(-3) M), an inhibitor of superoxide production via the cyclooxygenase pathway. We conclude from these data that the endothelium-derived contracting factor (EDCF) produced in SHR renal arteries is most likely PGH2 whereas the contractile factor produced in mesenteric arteries is superoxide.", "contents": "Endothelial dysfunction of resistance arteries of spontaneously hypertensive rats. Vascular relaxations are impaired in adult spontaneously hypertensive rats (SHRs) because of increased production of endothelium-derived, cyclooxygenase-dependent contractile factors. The objectives of the present study were to determine whether alterations in endothelial function precede the development of hypertension in SHRs and to characterize the contractile factor(s) produced by SHR endothelial cells. Mean systolic blood pressures were minimally (6 mm Hg) higher at 4 weeks of age in SHRs than in Wistar-Kyoto (WKY) rats. Endothelium-mediated relaxations of mesenteric and renal resistance arteries from SHRs and WKY rats were compared in myographs and arteriographs in paired experiments. Acetylcholine (ACh, 10(-9) to 10(-7) M) induced endothelium-dependent relaxations in precontracted mesenteric and renal resistance arteries that were similar in SHRs and WKY rats. At higher concentrations of ACh (10(-6) to 10(-5) M), relaxations were replaced by contractile responses in SHR but not in WKY rat resistance arteries. The contractile responses were endothelium dependent and were inhibited by indomethacin in both mesenteric and renal arteries. Thus, endothelial dysfunction precedes and may contribute to the development of accelerated hypertension in SHRs. SQ 29548, a prostaglandin H2 (PGH2)-thromboxane A2 receptor antagonist, blocked the contractile responses in renal but not in mesenteric resistance arteries. The contractile responses in mesenteric arteries were inhibited by 3-amino-1,2,4-triazole (10(-3) M), an inhibitor of superoxide production via the cyclooxygenase pathway. We conclude from these data that the endothelium-derived contracting factor (EDCF) produced in SHR renal arteries is most likely PGH2 whereas the contractile factor produced in mesenteric arteries is superoxide."} {"id": "PMID:1282967", "title": "Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension.", "content": "Endothelium-dependent vasodilation is reduced in essential hypertensive subjects. To evaluate whether this abnormality is a primary defect or is a consequence of blood pressure increment, in offspring of essential hypertensive and normotensive subjects (n = 13 subjects for each group) matched for age, sex, body weight, and blood pressure, we studied the response of forearm vasculature to acetylcholine (ACh) (an endothelium-dependent vasodilator), sodium nitroprusside (a direct vasodilator of vascular smooth muscle), and forearm ischemia (13 min plus 1 min of exercise) to induce maximal vasodilation. Drugs were infused into the brachial artery at cumulative doses (ACh: 0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 ml of forearm tissue/min; sodium nitroprusside: 1, 3, and 10 micrograms/100 ml of forearm tissue/min) while forearm blood flow was measured by strain-gauge venous plethysmography. The intra-arterial blood pressure and heart rate were continuously monitored. Despite a comparable forearm vascular response to sodium nitroprusside and to forearm ischemia, the effect of ACh was significantly (p < 0.001) reduced in offspring of hypertensive subjects compared to the offspring of normotensive subjects. These data indicate that ACh-mediated forearm vasodilation is reduced in normotensive subjects with a familial history of essential hypertension, a finding that suggests that endothelium dysfunction can precede the appearance of hypertension and that this abnormality might play a role in the pathogenesis of essential hypertension.", "contents": "Endothelium-dependent forearm vasodilation is reduced in normotensive subjects with familial history of hypertension. Endothelium-dependent vasodilation is reduced in essential hypertensive subjects. To evaluate whether this abnormality is a primary defect or is a consequence of blood pressure increment, in offspring of essential hypertensive and normotensive subjects (n = 13 subjects for each group) matched for age, sex, body weight, and blood pressure, we studied the response of forearm vasculature to acetylcholine (ACh) (an endothelium-dependent vasodilator), sodium nitroprusside (a direct vasodilator of vascular smooth muscle), and forearm ischemia (13 min plus 1 min of exercise) to induce maximal vasodilation. Drugs were infused into the brachial artery at cumulative doses (ACh: 0.15, 0.45, 1.5, 4.5, and 15 micrograms/100 ml of forearm tissue/min; sodium nitroprusside: 1, 3, and 10 micrograms/100 ml of forearm tissue/min) while forearm blood flow was measured by strain-gauge venous plethysmography. The intra-arterial blood pressure and heart rate were continuously monitored. Despite a comparable forearm vascular response to sodium nitroprusside and to forearm ischemia, the effect of ACh was significantly (p < 0.001) reduced in offspring of hypertensive subjects compared to the offspring of normotensive subjects. These data indicate that ACh-mediated forearm vasodilation is reduced in normotensive subjects with a familial history of essential hypertension, a finding that suggests that endothelium dysfunction can precede the appearance of hypertension and that this abnormality might play a role in the pathogenesis of essential hypertension."} {"id": "PMID:1282968", "title": "L-arginine as an antihypertensive agent.", "content": "L-Arginine, the precursor of endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), was administered intravenously in five patients with essential hypertension, one with renovascular hypertension, one with primary aldosteronism, and one with Cushing's syndrome. During the administration, the mean arterial pressure decreased concomitantly with an elevation of cardiac output and a fall in total peripheral resistance in all cases. Indicators of NO release in vivo such as plasma concentrations of L-citrulline and urinary excretion of nitrite/nitrate increased simultaneously during the administration. These results suggest that exogenous L-arginine can produce a vasodilatory effect via stimulating NO release in hypertensives.", "contents": "L-arginine as an antihypertensive agent. L-Arginine, the precursor of endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), was administered intravenously in five patients with essential hypertension, one with renovascular hypertension, one with primary aldosteronism, and one with Cushing's syndrome. During the administration, the mean arterial pressure decreased concomitantly with an elevation of cardiac output and a fall in total peripheral resistance in all cases. Indicators of NO release in vivo such as plasma concentrations of L-citrulline and urinary excretion of nitrite/nitrate increased simultaneously during the administration. These results suggest that exogenous L-arginine can produce a vasodilatory effect via stimulating NO release in hypertensives."} {"id": "PMID:1282969", "title": "Endothelium-dependent and -independent vasodilation and reactive hyperemia in healthy smokers.", "content": "Although cigarette smoking elicits a transient increase in peripheral vascular resistance in humans, the basal blood pressure (BP) is usually slightly lower in smokers. We hypothesized that this may be due to a compensatory increase in sensitivity in smokers to endogenous vasodilators. To test this, we studied endothelium-dependent and -independent vasodilator responses, and reactive hyperemia (RH) in the forearm of 25 healthy subjects [11 smokers (S) and 14 nonsmokers (NS)]. Endothelium-dependent vasodilation was induced by infusion into a brachial artery of stepwise increasing dosages of acetylcholine (ACh, 10-60 micrograms/kg/min) and endothelium-independent vasodilation by a similar infusion of nitroprusside (N, 1-6 micrograms/kg/min). RH was induced by release of a 5-min upper arm arterial occlusion. Forearm blood flow (FBF) was recorded by plethysmography. Endothelium-dependent vasodilation was more pronounced in S than in NS (p < 0.01), the maximal FBF during infusion of ACh being 20 +/- 6 and 14 +/- 4 ml/100 ml/min, respectively. Endothelium-independent vasodilation was also larger in S than in NS (p < 0.001), the maximal FBF during infusion of N being 14 +/- 3 and 12 +/- 2 ml/100 ml/min, respectively. ACh-induced vasodilator responses in S and NS were completely blocked by atropine. They were not decreased by trimethaphan, a nicotinic receptor inhibitor. RH was slightly more pronounced in S than in NS (p < 0.02), the postocclusive FBF 15 s after release of the occlusion being 25 +/- 4 and 21 +/- 3 ml/100 ml/min, respectively We propose that cigarette smoking increases the sensitivity of the vascular smooth muscle to vasodilator stimuli.", "contents": "Endothelium-dependent and -independent vasodilation and reactive hyperemia in healthy smokers. Although cigarette smoking elicits a transient increase in peripheral vascular resistance in humans, the basal blood pressure (BP) is usually slightly lower in smokers. We hypothesized that this may be due to a compensatory increase in sensitivity in smokers to endogenous vasodilators. To test this, we studied endothelium-dependent and -independent vasodilator responses, and reactive hyperemia (RH) in the forearm of 25 healthy subjects [11 smokers (S) and 14 nonsmokers (NS)]. Endothelium-dependent vasodilation was induced by infusion into a brachial artery of stepwise increasing dosages of acetylcholine (ACh, 10-60 micrograms/kg/min) and endothelium-independent vasodilation by a similar infusion of nitroprusside (N, 1-6 micrograms/kg/min). RH was induced by release of a 5-min upper arm arterial occlusion. Forearm blood flow (FBF) was recorded by plethysmography. Endothelium-dependent vasodilation was more pronounced in S than in NS (p < 0.01), the maximal FBF during infusion of ACh being 20 +/- 6 and 14 +/- 4 ml/100 ml/min, respectively. Endothelium-independent vasodilation was also larger in S than in NS (p < 0.001), the maximal FBF during infusion of N being 14 +/- 3 and 12 +/- 2 ml/100 ml/min, respectively. ACh-induced vasodilator responses in S and NS were completely blocked by atropine. They were not decreased by trimethaphan, a nicotinic receptor inhibitor. RH was slightly more pronounced in S than in NS (p < 0.02), the postocclusive FBF 15 s after release of the occlusion being 25 +/- 4 and 21 +/- 3 ml/100 ml/min, respectively We propose that cigarette smoking increases the sensitivity of the vascular smooth muscle to vasodilator stimuli."} {"id": "PMID:1282970", "title": "Endothelium-derived relaxing factor modulates the atherothrombogenic effects of homocysteine.", "content": "Hyperhomocysteinemia is a risk factor for atherosclerosis, and is found in the heterozygous form in approximately one-third of all individuals with coronary artery disease. The sulfhydryl group of homocysteine has been viewed as contributing to the atherogenic effects of this low-molecular-weight thiol, largely as a consequence of facilitating the generation of hydrogen peroxide from oxygen. Hydrogen peroxide, in turn, is presumed to induce dysfunction and damage to the endothelial cell, leading to attenuation of its antithrombotic and vasodilatory properties. As we have shown that endothelium-derived relaxing factor (EDRF) and other oxides of nitrogen can form adducts with thiols, we hypothesized that EDRF released from normal endothelium S-nitrosates homocysteine, rendering it nontoxic to the endothelium. We show that EDRF released from endothelial cells in the presence of homocysteine can lead to the formation of S-nitrosohomocysteine; that, like other S-nitrosothiols, S-nitrosohomocysteine induces vasorelaxation and platelet inhibition; and that, in contrast to homocysteine, S-nitrosohomocysteine does not support hydrogen peroxide generation and does not lead to endothelial dysfunction. These data suggest that normal endothelial cells modulate the adverse effects of homocysteine by facilitating the formation of the EDRF adduct, S-nitrosohomocysteine. The toxic effects of homocysteine may, then, result from an inability of the endothelium to sustain adequate production of EDRF in the face of elevated homocysteine concentration.", "contents": "Endothelium-derived relaxing factor modulates the atherothrombogenic effects of homocysteine. Hyperhomocysteinemia is a risk factor for atherosclerosis, and is found in the heterozygous form in approximately one-third of all individuals with coronary artery disease. The sulfhydryl group of homocysteine has been viewed as contributing to the atherogenic effects of this low-molecular-weight thiol, largely as a consequence of facilitating the generation of hydrogen peroxide from oxygen. Hydrogen peroxide, in turn, is presumed to induce dysfunction and damage to the endothelial cell, leading to attenuation of its antithrombotic and vasodilatory properties. As we have shown that endothelium-derived relaxing factor (EDRF) and other oxides of nitrogen can form adducts with thiols, we hypothesized that EDRF released from normal endothelium S-nitrosates homocysteine, rendering it nontoxic to the endothelium. We show that EDRF released from endothelial cells in the presence of homocysteine can lead to the formation of S-nitrosohomocysteine; that, like other S-nitrosothiols, S-nitrosohomocysteine induces vasorelaxation and platelet inhibition; and that, in contrast to homocysteine, S-nitrosohomocysteine does not support hydrogen peroxide generation and does not lead to endothelial dysfunction. These data suggest that normal endothelial cells modulate the adverse effects of homocysteine by facilitating the formation of the EDRF adduct, S-nitrosohomocysteine. The toxic effects of homocysteine may, then, result from an inability of the endothelium to sustain adequate production of EDRF in the face of elevated homocysteine concentration."} {"id": "PMID:1282971", "title": "Selective muscarinic alterations of nitric oxide-mediated relaxations by neointima.", "content": "During neointima formation, which is an early and essential step in the development of atherosclerosis, endothelium-independent relaxations (nitroglycerin, 3-morpholinosydnonimine) are preserved, whereas muscarinic endothelium-dependent relaxation becomes impaired. The present study was undertaken to determine the selectivity of this impairment. The neointima was induced by positioning a nonocclusive, soft silicone collar around the left carotid artery of rabbits. The contralateral artery served as a control. Seven days later, vascular rings were mounted in organ chambers, contracted with phenylephrine (0.35 microM), and cumulative dose-relaxation curves were made. Intima-bearing vessels were less sensitive to acetylcholine, confirming the original observation. In contrast, the dose-relaxation curves for substance P and for the calcium ionophore A23187 were not altered in the presence of neointima. The curve for ATP was even shifted to the left. These results suggest that the nitric oxide synthase: cyclic GMP system remains intact in intima-bearing vessels and that the diminished endothelium-dependent relaxations are due to a selective alteration of the muscarinic receptors.", "contents": "Selective muscarinic alterations of nitric oxide-mediated relaxations by neointima. During neointima formation, which is an early and essential step in the development of atherosclerosis, endothelium-independent relaxations (nitroglycerin, 3-morpholinosydnonimine) are preserved, whereas muscarinic endothelium-dependent relaxation becomes impaired. The present study was undertaken to determine the selectivity of this impairment. The neointima was induced by positioning a nonocclusive, soft silicone collar around the left carotid artery of rabbits. The contralateral artery served as a control. Seven days later, vascular rings were mounted in organ chambers, contracted with phenylephrine (0.35 microM), and cumulative dose-relaxation curves were made. Intima-bearing vessels were less sensitive to acetylcholine, confirming the original observation. In contrast, the dose-relaxation curves for substance P and for the calcium ionophore A23187 were not altered in the presence of neointima. The curve for ATP was even shifted to the left. These results suggest that the nitric oxide synthase: cyclic GMP system remains intact in intima-bearing vessels and that the diminished endothelium-dependent relaxations are due to a selective alteration of the muscarinic receptors."} {"id": "PMID:1282972", "title": "Release of contracting autacoids by aortae of normal and atherosclerotic rabbits.", "content": "The aim of our study was to examine the release of various lipid and peptide contracting autacoids by aortae of normal and atherosclerotic rabbits. Leukotriene (LT) E4, an enzymatic derivative of LTC4, thromboxane (Tx) B2, and endothelin-1 (ET-1) were measured by radioimmunoassay techniques in aortic preparations of normal and cholesterol-fed rabbits. Intact aortae of normal rabbits incubated with the calcium ionophore A23187 for 1 h at 37 degrees C released LTE4 and TxB2 (22 +/- 3.5 and 14.8 +/- 2 pg/mg of tissue, respectively, mean +/- SEM, n = 33). Removal of aortic endothelium was associated with a significant reduction in LTE4 (44%) and TxB2 (58%) release. In aortic preparations from cholesterol-fed rabbits, the release of LTE4 was significantly enhanced (41 +/- 8 pg/mg of tissue, mean +/- SEM, n = 27) whereas TxB2 was not significantly altered. No detectable amounts of ET-1 were measured after 1 h of incubation. However, at 4 h, an endothelium-dependent release of ET-1 from normal aortae was demonstrated. In atherosclerotic aortae, ET-1 release was significantly higher than in controls (10 +/- 1.3 vs. 5 +/- 0.5 pg/cm2, mean +/- SEM, n = 16). We conclude that enhanced formation of vasoconstrictor autacoids may contribute to altered vasomotion of atherosclerotic blood vessels.", "contents": "Release of contracting autacoids by aortae of normal and atherosclerotic rabbits. The aim of our study was to examine the release of various lipid and peptide contracting autacoids by aortae of normal and atherosclerotic rabbits. Leukotriene (LT) E4, an enzymatic derivative of LTC4, thromboxane (Tx) B2, and endothelin-1 (ET-1) were measured by radioimmunoassay techniques in aortic preparations of normal and cholesterol-fed rabbits. Intact aortae of normal rabbits incubated with the calcium ionophore A23187 for 1 h at 37 degrees C released LTE4 and TxB2 (22 +/- 3.5 and 14.8 +/- 2 pg/mg of tissue, respectively, mean +/- SEM, n = 33). Removal of aortic endothelium was associated with a significant reduction in LTE4 (44%) and TxB2 (58%) release. In aortic preparations from cholesterol-fed rabbits, the release of LTE4 was significantly enhanced (41 +/- 8 pg/mg of tissue, mean +/- SEM, n = 27) whereas TxB2 was not significantly altered. No detectable amounts of ET-1 were measured after 1 h of incubation. However, at 4 h, an endothelium-dependent release of ET-1 from normal aortae was demonstrated. In atherosclerotic aortae, ET-1 release was significantly higher than in controls (10 +/- 1.3 vs. 5 +/- 0.5 pg/cm2, mean +/- SEM, n = 16). We conclude that enhanced formation of vasoconstrictor autacoids may contribute to altered vasomotion of atherosclerotic blood vessels."} {"id": "PMID:1282973", "title": "L-arginine improves endothelium-dependent relaxation of conductance and resistance coronary arteries in coronary artery disease.", "content": "To assess the ability of L-arginine to improve endothelium-dependent vasodilation in atheromatous coronary arteries, we determined whether intracoronary infusion of L-arginine could improve coronary vascular reactivity to acetylcholine (ACh) examining both conductance and resistance vessels. Coronary blood flow velocity was assessed by positioning a 3 Fr Doppler catheter into the proximal coronary artery segment (six left anterior descending and one circumflex coronary artery). Computed quantitative angiography allowed the measurement of distal diameters. After baseline measurements, ACh was infused at incremental infusion rates through the Doppler lumen catheter (3 min period each) to obtain the estimated concentrations of 5 x 10(-7), 10(-6), and 5 x 10(-6) M. After returning to baseline, L-arginine was infused at the rate of 25 mg/min (10(-3) M) through the Doppler lumen catheter. Infusion of ACh was then repeated according to the same protocol than in the absence of L-arginine. The heart rate and mean arterial blood pressure did not change at any step of the protocol. Infusion of ACh induced dose-dependent vasoconstriction of coronary distal segments with a reduction in coronary distal segments by 39 +/- 15% at 5 x 10(-6) M (p < 0.01). During infusion of L-arginine, the coronary diameter was reduced by only 16 +/- 10% (p < 0.05) at the highest ACh dose. The coronary blood flow velocity increased by 100 +/- 15% at 5 x 10(-7) M ACh (p < 0.05) but only to 16 +/- 15% at 5 x 10(-6) M ACh (NS).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "L-arginine improves endothelium-dependent relaxation of conductance and resistance coronary arteries in coronary artery disease. To assess the ability of L-arginine to improve endothelium-dependent vasodilation in atheromatous coronary arteries, we determined whether intracoronary infusion of L-arginine could improve coronary vascular reactivity to acetylcholine (ACh) examining both conductance and resistance vessels. Coronary blood flow velocity was assessed by positioning a 3 Fr Doppler catheter into the proximal coronary artery segment (six left anterior descending and one circumflex coronary artery). Computed quantitative angiography allowed the measurement of distal diameters. After baseline measurements, ACh was infused at incremental infusion rates through the Doppler lumen catheter (3 min period each) to obtain the estimated concentrations of 5 x 10(-7), 10(-6), and 5 x 10(-6) M. After returning to baseline, L-arginine was infused at the rate of 25 mg/min (10(-3) M) through the Doppler lumen catheter. Infusion of ACh was then repeated according to the same protocol than in the absence of L-arginine. The heart rate and mean arterial blood pressure did not change at any step of the protocol. Infusion of ACh induced dose-dependent vasoconstriction of coronary distal segments with a reduction in coronary distal segments by 39 +/- 15% at 5 x 10(-6) M (p < 0.01). During infusion of L-arginine, the coronary diameter was reduced by only 16 +/- 10% (p < 0.05) at the highest ACh dose. The coronary blood flow velocity increased by 100 +/- 15% at 5 x 10(-7) M ACh (p < 0.05) but only to 16 +/- 15% at 5 x 10(-6) M ACh (NS).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282974", "title": "Measurements of serum levels of nitrate ions in men and women: implications of endothelium-derived relaxing factor in blood pressure regulation and atherosclerosis.", "content": "As endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitric ions, we measured serum levels of nitrate (NO3-) concentrations as an index of endothelium-derived NO, to assess its role in blood pressure regulation. Because serum NO3- levels in men were significantly elevated compared to those in women, data from these two groups were analyzed separately. In men, multiple regression analysis revealed that NO3- significantly correlated with age, systolic blood pressure, body mass index (BMI), and total cholesterol. Blood pressure correlated with age, BMI, and NO3- with multivariate analysis. In women, NO3- significantly correlated with age, systolic blood pressure, and total cholesterol with a simple correlation. With multiple regression analysis, serum NO3- highly correlated with serum levels of triglyceride and total cholesterol and age. The blood pressure correlated with four parameters, i.e., total cholesterol, age, BMI, and NO3-. In summary, serum NO3- levels seem to relate to serum lipids and glucose levels and blood pressure, which strongly suggests that production of endothelium-derived NO is increased in the atherosclerotic process.", "contents": "Measurements of serum levels of nitrate ions in men and women: implications of endothelium-derived relaxing factor in blood pressure regulation and atherosclerosis. As endothelium-derived nitric oxide (NO) is a potent vasodilator and degraded into nitric ions, we measured serum levels of nitrate (NO3-) concentrations as an index of endothelium-derived NO, to assess its role in blood pressure regulation. Because serum NO3- levels in men were significantly elevated compared to those in women, data from these two groups were analyzed separately. In men, multiple regression analysis revealed that NO3- significantly correlated with age, systolic blood pressure, body mass index (BMI), and total cholesterol. Blood pressure correlated with age, BMI, and NO3- with multivariate analysis. In women, NO3- significantly correlated with age, systolic blood pressure, and total cholesterol with a simple correlation. With multiple regression analysis, serum NO3- highly correlated with serum levels of triglyceride and total cholesterol and age. The blood pressure correlated with four parameters, i.e., total cholesterol, age, BMI, and NO3-. In summary, serum NO3- levels seem to relate to serum lipids and glucose levels and blood pressure, which strongly suggests that production of endothelium-derived NO is increased in the atherosclerotic process."} {"id": "PMID:1282975", "title": "Membrane physiological reactions of human arteriosclerotic coronary arteries to hypoxia.", "content": "Human coronary arteries were taken from heart transplant patients. Arteriosclerotic arteries were more depolarized and constricted over the whole PO2 range between 535 and 0 mm Hg. During oxygen deficiency, control preparations showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. In normal coronary arteries, indomethacin reduced the hypoxic hyperpolarization and dilation at 30 mm Hg PO2 by about 51%. The reduction was 26% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (74%) restriction of dilatory vascular reactivity. The relationship was quite similar for a carbogen Krebs solution. The hyperpolarizing and dilatory contribution by prostacyclin was 32% in normal and 12% in arteriosclerotic coronary arteries. The remainder could be attributed to the basal release of the endothelial dilator endothelium-derived hyperpolarizing factor (EDHF). Thus, it may be concluded that in arteriosclerotic blood vessels, prostacyclin (PGI2) synthesis and release are predominantly diminished. Finally, we found that the ratio PGI2/EDHF in the voltage and tension changes strongly shifted to the PGI2 side with a declining oxygen concentration. This is true for normal and arteriosclerotic vessels. In accordance with the activation curve for vascular smooth muscle, the hyperpolarization leads to relaxation via a closure of Ca2+ channels. Hyperpolarization of 2.5 mV reduces the tension developed by one-half.", "contents": "Membrane physiological reactions of human arteriosclerotic coronary arteries to hypoxia. Human coronary arteries were taken from heart transplant patients. Arteriosclerotic arteries were more depolarized and constricted over the whole PO2 range between 535 and 0 mm Hg. During oxygen deficiency, control preparations showed a maximal hyperpolarization of delta V = 10.9 mV and a maximal relaxation of delta T = 0.466 g. Arteriosclerotic arteries, however, became hyperpolarized by merely delta V = 7.1 mV and relaxed by delta T = 0.258 g. In normal coronary arteries, indomethacin reduced the hypoxic hyperpolarization and dilation at 30 mm Hg PO2 by about 51%. The reduction was 26% in arteriosclerotic vessels. The complete removal of the endothelium caused a 49% (74%) restriction of dilatory vascular reactivity. The relationship was quite similar for a carbogen Krebs solution. The hyperpolarizing and dilatory contribution by prostacyclin was 32% in normal and 12% in arteriosclerotic coronary arteries. The remainder could be attributed to the basal release of the endothelial dilator endothelium-derived hyperpolarizing factor (EDHF). Thus, it may be concluded that in arteriosclerotic blood vessels, prostacyclin (PGI2) synthesis and release are predominantly diminished. Finally, we found that the ratio PGI2/EDHF in the voltage and tension changes strongly shifted to the PGI2 side with a declining oxygen concentration. This is true for normal and arteriosclerotic vessels. In accordance with the activation curve for vascular smooth muscle, the hyperpolarization leads to relaxation via a closure of Ca2+ channels. Hyperpolarization of 2.5 mV reduces the tension developed by one-half."} {"id": "PMID:1282976", "title": "Characterization of serine protease-derived metabolites of big endothelin in the cytosolic fraction from human polymorphonuclear leukocytes.", "content": "We have characterized by bioassay and reversed-phase high-performance liquid chromatography analysis (rp-HPLC) the conversion of human big endothelin-1 (bET-1) to endothelin-1 (ET-1) by the cytosolic fraction from human polymorphonuclear leukocytes (PMNs). Either the general serine protease inhibitor 3,4-dichloroisocoumarin (DCI; 50 microM) or the selective elastase inhibitor ONO-5046 (100 microM) blocked the formation of ET-1 from bET-1. Interestingly, human leukocyte elastase formed some of the same products from bET-1 as the PMN cytosol, but generated negligible amounts of ET-1. However, coincubation of the elastase-derived fragments of bET-1 with the PMN cytosol in the presence of ONO-5046 resulted in a 17-fold increase in the formation of ET-1, indicating that an elastase-derived intermediate of bET-1 was subsequently cleaved by a soluble protease(s) to form mature ET-1. We have identified by electrospray-mass spectrometry (ESMS) analysis this intermediate as bET-1(1-22). Analysis of bET-1 digestion by human leukocyte cathepsin G revealed the formation of a biologically active metabolite chromatographically distinct from ET-1, identified as bET-1(1-31) by ESMS. These findings indicate the presence of complex enzyme systems in human PMNs capable of activating bET-1.", "contents": "Characterization of serine protease-derived metabolites of big endothelin in the cytosolic fraction from human polymorphonuclear leukocytes. We have characterized by bioassay and reversed-phase high-performance liquid chromatography analysis (rp-HPLC) the conversion of human big endothelin-1 (bET-1) to endothelin-1 (ET-1) by the cytosolic fraction from human polymorphonuclear leukocytes (PMNs). Either the general serine protease inhibitor 3,4-dichloroisocoumarin (DCI; 50 microM) or the selective elastase inhibitor ONO-5046 (100 microM) blocked the formation of ET-1 from bET-1. Interestingly, human leukocyte elastase formed some of the same products from bET-1 as the PMN cytosol, but generated negligible amounts of ET-1. However, coincubation of the elastase-derived fragments of bET-1 with the PMN cytosol in the presence of ONO-5046 resulted in a 17-fold increase in the formation of ET-1, indicating that an elastase-derived intermediate of bET-1 was subsequently cleaved by a soluble protease(s) to form mature ET-1. We have identified by electrospray-mass spectrometry (ESMS) analysis this intermediate as bET-1(1-22). Analysis of bET-1 digestion by human leukocyte cathepsin G revealed the formation of a biologically active metabolite chromatographically distinct from ET-1, identified as bET-1(1-31) by ESMS. These findings indicate the presence of complex enzyme systems in human PMNs capable of activating bET-1."} {"id": "PMID:1282977", "title": "Endothelium-dependent forearm vasodilation to acetylcholine but not to substance P is impaired in patients with heart failure.", "content": "It has been shown that endothelium-dependent vasorelaxation in response to muscarinic stimulation is attenuated in patients as well as animals with heart failure. This study aimed to determine if endothelium-dependent forearm vasodilation evoked with substance P (SP) as well as acetylcholine (ACh) was impaired in patients with heart failure. Forearm blood flow was measured using a strain-gauge plethysmograph and forearm vascular responses to intra-arterial infusions of ACh, SP, or sodium nitroprusside (SNP) at graded doses were examined. The drugs caused the dose-dependent increases in forearm blood flow (FBF) and the decreases in forearm vascular resistance (FVR) in patients with heart failure as well as normal subjects. However, the percent decreases in FVR by ACh were less in patients with heart failure than in normal subjects (p < 0.01). In contrast, the percent decreases in FVR by SP or SNP did not differ between the two groups. These results suggest that endothelium-dependent vasodilation of forearm resistance vessels via muscarinic receptors is specifically impaired, whereas via SP receptors, is preserved in patients with heart failure.", "contents": "Endothelium-dependent forearm vasodilation to acetylcholine but not to substance P is impaired in patients with heart failure. It has been shown that endothelium-dependent vasorelaxation in response to muscarinic stimulation is attenuated in patients as well as animals with heart failure. This study aimed to determine if endothelium-dependent forearm vasodilation evoked with substance P (SP) as well as acetylcholine (ACh) was impaired in patients with heart failure. Forearm blood flow was measured using a strain-gauge plethysmograph and forearm vascular responses to intra-arterial infusions of ACh, SP, or sodium nitroprusside (SNP) at graded doses were examined. The drugs caused the dose-dependent increases in forearm blood flow (FBF) and the decreases in forearm vascular resistance (FVR) in patients with heart failure as well as normal subjects. However, the percent decreases in FVR by ACh were less in patients with heart failure than in normal subjects (p < 0.01). In contrast, the percent decreases in FVR by SP or SNP did not differ between the two groups. These results suggest that endothelium-dependent vasodilation of forearm resistance vessels via muscarinic receptors is specifically impaired, whereas via SP receptors, is preserved in patients with heart failure."} {"id": "PMID:1282978", "title": "Endothelin release and shift in prostaglandin balance are involved in the modulation of vascular tone by recombinant erythropoietin.", "content": "Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rhEPO). We investigated the effect of rhEPO on the vascular tone of rabbit aorta. rhEPO had no direct vasoconstrictor effect, but it enhanced norepinephrine (NE)-induced contractions of rabbit aortic rings. Relaxations to acetylcholine (ACh, 1 microM) were unaltered in the presence or absence of rhEPO, indicating that the endothelium-dependent NO pathway was not affected by rhEPO. In rings of human renal artery and rabbit aorta, rhEPO (200 U/ml) increased the synthesis of constrictor prostanoids. The cyclooxygenase inhibitors indomethacin and aspirin abolished the increase in prostanoid production. However, they did not completely suppress the rhEPO-induced enhancement of NE contractions in rabbit aorta. We further investigated the effect of rhEPO on prostanoid and endothelin-1 synthesis in cultured human endothelial cells. Endothelial cells from human umbilical veins (HUVEC) were isolated and cultured. After incubation with rhEPO, the formation of prostaglandin (PG) I2 (analyzed as its stable metabolite 6-keto-PGF1 alpha), PGF2 alpha, PGE2, thromboxane (Tx) B2, and of endothelin-1 (ET-1) was measured by radioimmunoassay (RIA). rhEPO (200 U/ml) increased the formation of PGF2 alpha and TxB2 and decreased the formation of PGI2 in HUVEC. The release of ET-1 was increased by nearly 90% in the presence of rhEPO (200 U/ml). We conclude that a shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET-1 may contribute to the hypertensive side effect of rhEPO therapy. ET-1 may at least in part be responsible for the unexpectedly low inhibitory effect of indomethacin on rhEPO-enhanced contractions of rabbit aorta.", "contents": "Endothelin release and shift in prostaglandin balance are involved in the modulation of vascular tone by recombinant erythropoietin. Hypertension is the main side effect developing in patients suffering from renal anemia who are treated with recombinant human erythropoietin (rhEPO). We investigated the effect of rhEPO on the vascular tone of rabbit aorta. rhEPO had no direct vasoconstrictor effect, but it enhanced norepinephrine (NE)-induced contractions of rabbit aortic rings. Relaxations to acetylcholine (ACh, 1 microM) were unaltered in the presence or absence of rhEPO, indicating that the endothelium-dependent NO pathway was not affected by rhEPO. In rings of human renal artery and rabbit aorta, rhEPO (200 U/ml) increased the synthesis of constrictor prostanoids. The cyclooxygenase inhibitors indomethacin and aspirin abolished the increase in prostanoid production. However, they did not completely suppress the rhEPO-induced enhancement of NE contractions in rabbit aorta. We further investigated the effect of rhEPO on prostanoid and endothelin-1 synthesis in cultured human endothelial cells. Endothelial cells from human umbilical veins (HUVEC) were isolated and cultured. After incubation with rhEPO, the formation of prostaglandin (PG) I2 (analyzed as its stable metabolite 6-keto-PGF1 alpha), PGF2 alpha, PGE2, thromboxane (Tx) B2, and of endothelin-1 (ET-1) was measured by radioimmunoassay (RIA). rhEPO (200 U/ml) increased the formation of PGF2 alpha and TxB2 and decreased the formation of PGI2 in HUVEC. The release of ET-1 was increased by nearly 90% in the presence of rhEPO (200 U/ml). We conclude that a shift in the balance of constrictor and relaxing prostanoids as well as an increased synthesis of ET-1 may contribute to the hypertensive side effect of rhEPO therapy. ET-1 may at least in part be responsible for the unexpectedly low inhibitory effect of indomethacin on rhEPO-enhanced contractions of rabbit aorta."} {"id": "PMID:1282979", "title": "Protein kinase C regulates activation of mitogen-activated protein kinase and induction of proto-oncogene c-fos by endothelin-1.", "content": "Endothelins (ETs) are potent regulatory peptides that cause numerous phenotypic changes in glomerular mesangial cells including differential regulation of gene expression and mitogenesis. Although the second messengers produced by activated ET receptors are well characterized, little is known about pathways of nuclear signaling. In this report, we evaluate the role of a well-characterized effector linked to ET receptor activation, protein kinase C, in the stimulation of mitogen-activated protein kinase (p42-44mapk) and the induction of protooncogene c-fos. Stimulation of protein kinase C by phorbol ester was sufficient to increase p42-44mapk activity and induce c-fos. When ET-1 was added to mesangial cells depleted of protein kinase C, the increase in p42-44mapk was attenuated and the induction of c-fos was abolished. Taken together with previous data, these experiments suggest that protein kinase C, p42-44mapk, and c-fos constitute a pathway by which ET-1 regulates expression of mesangial cell genes. These effectors might have relevance to the role of ET-1 in cell growth and vascular remodeling.", "contents": "Protein kinase C regulates activation of mitogen-activated protein kinase and induction of proto-oncogene c-fos by endothelin-1. Endothelins (ETs) are potent regulatory peptides that cause numerous phenotypic changes in glomerular mesangial cells including differential regulation of gene expression and mitogenesis. Although the second messengers produced by activated ET receptors are well characterized, little is known about pathways of nuclear signaling. In this report, we evaluate the role of a well-characterized effector linked to ET receptor activation, protein kinase C, in the stimulation of mitogen-activated protein kinase (p42-44mapk) and the induction of protooncogene c-fos. Stimulation of protein kinase C by phorbol ester was sufficient to increase p42-44mapk activity and induce c-fos. When ET-1 was added to mesangial cells depleted of protein kinase C, the increase in p42-44mapk was attenuated and the induction of c-fos was abolished. Taken together with previous data, these experiments suggest that protein kinase C, p42-44mapk, and c-fos constitute a pathway by which ET-1 regulates expression of mesangial cell genes. These effectors might have relevance to the role of ET-1 in cell growth and vascular remodeling."} {"id": "PMID:1282980", "title": "Effects of endothelin-1 on vascular smooth muscle cell phenotypic differentiation.", "content": "Endothelin-1 (ET-1) produced by vascular endothelial cells has been proposed to act in a paracrine manner on adjacent smooth muscle cells (SMCs) in vivo, exerting a variety of short- and long-term effects. Although some of the in vitro ET-1-mediated effects are related to growth-promoting events, the physiological significance of these observations remains to be clarified. Reported discrepancies of the mitogenic potential of ET-1 may relate to differences in culturing conditions (submitogenic levels of serum in combination with ET-1). Because ET-1 has been implicated in proliferation of vascular SMCs (VSMCs) at sites of vascular injury, as well as pathological events during atherogenesis, a clarification of the mitogenic effects of ET-1 is important. This study demonstrates the possible autocrine role for ET-1 in the regulation of the vasculature, its influence on VSMC cell cycle, and autocrine and phenotypic regulation of VSMCs. Stimulation of quiescent VSMCs with a variety of peptides resulted in the secretion of biologically active ET-1 by VSMCs. In contrast to previous reports, long-term exposure (12-15 days) of VSMCs to ET-1 in nonmitogenic medium did not promote cycling of cells. On the contrary, ET-1 attenuated the cycling of VSMCs in the S and G2/M phases and interrupted progression through the cell cycle at late G1/early S phase. Subsequent to ET-1 exposure, VSMCs expressed increased levels of smooth muscle-specific alpha-actin. Therefore, autocrine-produced ET-1 may contribute to phenotypic differentiation of VSMCs.", "contents": "Effects of endothelin-1 on vascular smooth muscle cell phenotypic differentiation. Endothelin-1 (ET-1) produced by vascular endothelial cells has been proposed to act in a paracrine manner on adjacent smooth muscle cells (SMCs) in vivo, exerting a variety of short- and long-term effects. Although some of the in vitro ET-1-mediated effects are related to growth-promoting events, the physiological significance of these observations remains to be clarified. Reported discrepancies of the mitogenic potential of ET-1 may relate to differences in culturing conditions (submitogenic levels of serum in combination with ET-1). Because ET-1 has been implicated in proliferation of vascular SMCs (VSMCs) at sites of vascular injury, as well as pathological events during atherogenesis, a clarification of the mitogenic effects of ET-1 is important. This study demonstrates the possible autocrine role for ET-1 in the regulation of the vasculature, its influence on VSMC cell cycle, and autocrine and phenotypic regulation of VSMCs. Stimulation of quiescent VSMCs with a variety of peptides resulted in the secretion of biologically active ET-1 by VSMCs. In contrast to previous reports, long-term exposure (12-15 days) of VSMCs to ET-1 in nonmitogenic medium did not promote cycling of cells. On the contrary, ET-1 attenuated the cycling of VSMCs in the S and G2/M phases and interrupted progression through the cell cycle at late G1/early S phase. Subsequent to ET-1 exposure, VSMCs expressed increased levels of smooth muscle-specific alpha-actin. Therefore, autocrine-produced ET-1 may contribute to phenotypic differentiation of VSMCs."} {"id": "PMID:1282981", "title": "Effects of endothelin-1 and endothelin-3 on the isolated guinea pig ileum: role of Na+ ions and endothelin receptor subtypes.", "content": "Endothelin (ET)-1 and ET-3 induced a biphasic effect (relaxation followed by contraction) in the isolated guinea pig ileum. The contractile but not the relaxant component of the responses was concentration dependent in the dose range studied. Neuronal mechanisms, cyclic guanosine monophosphate (GMP), and adenosine triphosphate (ATP)-dependent K+ channels do not seem to be involved in the relaxing effect of the two isopeptides, since that effect was not affected by either tetrodotoxin, methylene blue, or glibenclamide. Both ET-1 and ET-3 induced tachyphylaxis (homologous desensitization), which was not fully reversed after a 3-h resting period. The responses to both peptides were dependent on the Na+ gradient across the smooth muscle cells, as they were inhibited in low-Na+ medium and after treatment of the preparation with ouabain. Verapamil affected both the relaxant and the contractile components of the responses to the two isopeptides, whereas phorbol-12,13-dibutyrate affected mainly the contractile component. These results suggest that the voltage-operated channels are important for both components of the response induced by ET-1 and ET-3, and that protein kinase C may downregulate Ca2+ signalling. Cross-tachyphylaxis studies between ET-1 and ET-3 suggest the existence of at least two ET receptor subtypes in the guinea pig ileum.", "contents": "Effects of endothelin-1 and endothelin-3 on the isolated guinea pig ileum: role of Na+ ions and endothelin receptor subtypes. Endothelin (ET)-1 and ET-3 induced a biphasic effect (relaxation followed by contraction) in the isolated guinea pig ileum. The contractile but not the relaxant component of the responses was concentration dependent in the dose range studied. Neuronal mechanisms, cyclic guanosine monophosphate (GMP), and adenosine triphosphate (ATP)-dependent K+ channels do not seem to be involved in the relaxing effect of the two isopeptides, since that effect was not affected by either tetrodotoxin, methylene blue, or glibenclamide. Both ET-1 and ET-3 induced tachyphylaxis (homologous desensitization), which was not fully reversed after a 3-h resting period. The responses to both peptides were dependent on the Na+ gradient across the smooth muscle cells, as they were inhibited in low-Na+ medium and after treatment of the preparation with ouabain. Verapamil affected both the relaxant and the contractile components of the responses to the two isopeptides, whereas phorbol-12,13-dibutyrate affected mainly the contractile component. These results suggest that the voltage-operated channels are important for both components of the response induced by ET-1 and ET-3, and that protein kinase C may downregulate Ca2+ signalling. Cross-tachyphylaxis studies between ET-1 and ET-3 suggest the existence of at least two ET receptor subtypes in the guinea pig ileum."} {"id": "PMID:1282982", "title": "Ischemia-induced changes in the immunoreactivity for endothelin and other vasoactive peptides in the brain of the Mongolian gerbil.", "content": "Immunoreactivity for vasoactive peptides [endothelin (ET); calcitonin gene-related peptide (CGRP); atrial natriuretic peptide (ANP); neuropeptide Y (NPY)] was investigated in nervous tissue of Mongolian gerbils in which the common carotid artery (CCA) was temporarily occluded (30 min-4 h) on one side, provoking transient unilateral ischemia at the forebrain level. Observations were carried out in a group of animals that were perfused promptly after CCA reopening, and in a group of animals that were perfused 12 h later. In animals of the first group, darker immunostaining was usually observed for most peptides in the forebrain ipsilateral to the CCA occlusion. Computer-assisted densitometric analysis showed that the asymmetry was relevant for ET, CGRP, and ANP, and almost undetectable for NPY. In animals of the second group, areas of tissue degeneration were observed. In these areas, ET immunoreactivity was markedly denser, whereas immunoreactivity for the remaining peptides was about at the background level. It is concluded that ischemia induces an increase in both vasoconstrictor and vasodilator peptides that in areas of moderate ischemia might maintain a residual tissue perfusion. In areas of severe hypoxia, a predominant ET-induced vasoconstriction would contribute to tissue damage.", "contents": "Ischemia-induced changes in the immunoreactivity for endothelin and other vasoactive peptides in the brain of the Mongolian gerbil. Immunoreactivity for vasoactive peptides [endothelin (ET); calcitonin gene-related peptide (CGRP); atrial natriuretic peptide (ANP); neuropeptide Y (NPY)] was investigated in nervous tissue of Mongolian gerbils in which the common carotid artery (CCA) was temporarily occluded (30 min-4 h) on one side, provoking transient unilateral ischemia at the forebrain level. Observations were carried out in a group of animals that were perfused promptly after CCA reopening, and in a group of animals that were perfused 12 h later. In animals of the first group, darker immunostaining was usually observed for most peptides in the forebrain ipsilateral to the CCA occlusion. Computer-assisted densitometric analysis showed that the asymmetry was relevant for ET, CGRP, and ANP, and almost undetectable for NPY. In animals of the second group, areas of tissue degeneration were observed. In these areas, ET immunoreactivity was markedly denser, whereas immunoreactivity for the remaining peptides was about at the background level. It is concluded that ischemia induces an increase in both vasoconstrictor and vasodilator peptides that in areas of moderate ischemia might maintain a residual tissue perfusion. In areas of severe hypoxia, a predominant ET-induced vasoconstriction would contribute to tissue damage."} {"id": "PMID:1282983", "title": "Molecular cloning of constitutive endothelial nitric oxide synthase: evidence for a family of related genes.", "content": "Nitric oxide (NO) is synthesized in vascular endothelial cells, and appears to play an important role in the control of blood pressure and platelet aggregation. A detailed understanding of the regulation of NO synthesis by endothelial cells has been hampered by the lack of molecular clones for endothelial NO synthase; we now report the isolation and characterization of such clones. The constitutive NO synthases present in endothelial cells and in brain share common biochemical and pharmacologic features. We purified NO synthase from bovine brain, and determined the amino acid sequence of several tryptic peptides. These sequence data were utilized to design PCR-generated NO synthase cDNA probes, which were used to isolate clones encoding NO synthase from a bovine aortic endothelial cell (BAEC) cDNA library. A full-length NO synthase cDNA clone was isolated, representing a protein of 1,205 amino acids with a molecular mass of 133 kDa. The deduced amino acid sequence of the BAEC NO synthase cDNA differs at numerous residues from the sequence determined for the purified bovine brain protein, and shows 50-60% sequence identity with recently isolated molecular clones for murine macrophage and rat brain NO synthase isoforms. Bovine genomic Southern blots probed with bovine brain and BAEC NO synthase cDNA probes identify distinct bands, indicating that these cDNAs are the products of different genes. Prolonged treatment of BAEC with the cytokine TNF alpha, which results in a marked increase in NO synthase activity, is associated with a decrease in the abundance of the 4.8-kb BAEC NO synthase transcript.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Molecular cloning of constitutive endothelial nitric oxide synthase: evidence for a family of related genes. Nitric oxide (NO) is synthesized in vascular endothelial cells, and appears to play an important role in the control of blood pressure and platelet aggregation. A detailed understanding of the regulation of NO synthesis by endothelial cells has been hampered by the lack of molecular clones for endothelial NO synthase; we now report the isolation and characterization of such clones. The constitutive NO synthases present in endothelial cells and in brain share common biochemical and pharmacologic features. We purified NO synthase from bovine brain, and determined the amino acid sequence of several tryptic peptides. These sequence data were utilized to design PCR-generated NO synthase cDNA probes, which were used to isolate clones encoding NO synthase from a bovine aortic endothelial cell (BAEC) cDNA library. A full-length NO synthase cDNA clone was isolated, representing a protein of 1,205 amino acids with a molecular mass of 133 kDa. The deduced amino acid sequence of the BAEC NO synthase cDNA differs at numerous residues from the sequence determined for the purified bovine brain protein, and shows 50-60% sequence identity with recently isolated molecular clones for murine macrophage and rat brain NO synthase isoforms. Bovine genomic Southern blots probed with bovine brain and BAEC NO synthase cDNA probes identify distinct bands, indicating that these cDNAs are the products of different genes. Prolonged treatment of BAEC with the cytokine TNF alpha, which results in a marked increase in NO synthase activity, is associated with a decrease in the abundance of the 4.8-kb BAEC NO synthase transcript.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282984", "title": "Substitution of lysine-181 to aspartic acid in the third transmembrane region of the endothelin (ET) type B receptor selectively reduces its high-affinity binding with ET-3 peptide.", "content": "In the G protein-coupled receptor family, a highly conserved aspartic acid located within the third transmembrane domain has been shown to be involved in ligand binding. Within the endothelin (ET) peptide receptor family, this aspartic acid has been replaced by a lysine. To assess the importance of this residue in ET binding, the lysine (position 181) of rat ET type B receptor was replaced by an aspartic acid. The effects on ligand binding and phosphoinositide turnover of both the wild-type and K181D mutant receptors were examined using transient receptor expression in COS-7 cells. Using [125I]ET-1 as the radioactive peptide ligand in displacement binding studies, the wild-type receptor displayed a typical non-isopeptide-selective binding profile with similar IC50 values (0.2-0.6 nM) for all three ET peptides (ET-1, ET-2, and ET-3). The mutant receptor showed an increase in IC50 values for ET-1 (5 nM), ET-2 (27 nM), and ET-3 (127 nM). The K181D mutant receptor still elicited full inositol phosphate (IP) accumulation responses in the presence of saturating concentrations of ETs (10 nM of ET-1, 100 nM of ET-2, or 1 microM of ET-3), indicating that the mutation did not affect G protein coupling.", "contents": "Substitution of lysine-181 to aspartic acid in the third transmembrane region of the endothelin (ET) type B receptor selectively reduces its high-affinity binding with ET-3 peptide. In the G protein-coupled receptor family, a highly conserved aspartic acid located within the third transmembrane domain has been shown to be involved in ligand binding. Within the endothelin (ET) peptide receptor family, this aspartic acid has been replaced by a lysine. To assess the importance of this residue in ET binding, the lysine (position 181) of rat ET type B receptor was replaced by an aspartic acid. The effects on ligand binding and phosphoinositide turnover of both the wild-type and K181D mutant receptors were examined using transient receptor expression in COS-7 cells. Using [125I]ET-1 as the radioactive peptide ligand in displacement binding studies, the wild-type receptor displayed a typical non-isopeptide-selective binding profile with similar IC50 values (0.2-0.6 nM) for all three ET peptides (ET-1, ET-2, and ET-3). The mutant receptor showed an increase in IC50 values for ET-1 (5 nM), ET-2 (27 nM), and ET-3 (127 nM). The K181D mutant receptor still elicited full inositol phosphate (IP) accumulation responses in the presence of saturating concentrations of ETs (10 nM of ET-1, 100 nM of ET-2, or 1 microM of ET-3), indicating that the mutation did not affect G protein coupling."} {"id": "PMID:1282985", "title": "Particulate and soluble bovine endothelial nitric oxide synthases are structurally similar proteins yet different from soluble brain nitric oxide synthase.", "content": "In cultured bovine aortic endothelial cells (BAECs), 95% of the total endothelial nitric oxide (NO) synthase (type III) activity was found in the particulate fraction and only 5% was found in the soluble fraction. The soluble and particulate endothelial NO synthase activities behaved similarly on anion-exchange and gel filtration chromatography, whereas the soluble brain NO synthase (type I) had chromatographic properties different from the type III endothelial NO synthases. We have purified the particulate endothelial NO synthase from cultured and native BAECs using affinity chromatography on 2',5'-ADP Sepharose followed by Superose 6 gel filtration chromatography. Subsequently, monoclonal antibodies were generated against the purified particulate endothelial NO synthase. In protein immunoblotting analyses, crude and partially purified samples of particulate and soluble type III endothelial NO synthase demonstrated a single band at a molecular mass of 135 kDa with monoclonal antibody (MAb) H32. Purified type I soluble brain NO synthase did not cross-react with MAb H32. These data indicate that the soluble and particulate endothelial NO synthase are structurally similar proteins and represent an isozyme that can be distinguished from the brain NO synthase.", "contents": "Particulate and soluble bovine endothelial nitric oxide synthases are structurally similar proteins yet different from soluble brain nitric oxide synthase. In cultured bovine aortic endothelial cells (BAECs), 95% of the total endothelial nitric oxide (NO) synthase (type III) activity was found in the particulate fraction and only 5% was found in the soluble fraction. The soluble and particulate endothelial NO synthase activities behaved similarly on anion-exchange and gel filtration chromatography, whereas the soluble brain NO synthase (type I) had chromatographic properties different from the type III endothelial NO synthases. We have purified the particulate endothelial NO synthase from cultured and native BAECs using affinity chromatography on 2',5'-ADP Sepharose followed by Superose 6 gel filtration chromatography. Subsequently, monoclonal antibodies were generated against the purified particulate endothelial NO synthase. In protein immunoblotting analyses, crude and partially purified samples of particulate and soluble type III endothelial NO synthase demonstrated a single band at a molecular mass of 135 kDa with monoclonal antibody (MAb) H32. Purified type I soluble brain NO synthase did not cross-react with MAb H32. These data indicate that the soluble and particulate endothelial NO synthase are structurally similar proteins and represent an isozyme that can be distinguished from the brain NO synthase."} {"id": "PMID:1282986", "title": "Nitric oxide synthase-catalyzed activation of oxygen and reduction of cytochromes: reaction mechanisms and possible physiological implications.", "content": "Purified cerebellar nitric oxide (NO) synthase was found to reduce molecular oxygen to hydrogen peroxide at low concentrations of its substrate L-arginine or its cofactor tetrahydrobiopterin. The characteristics of oxygen reduction appeared to be similar to NO synthesis, as both reactions required reduced nicotinamide adenine dinucleotide phosphate (NADPH), were dependent on Ca2+/calmodulin, and showed optimal reaction rates at slightly acidic conditions. The electron transport from NADPH to molecular oxygen is probably mediated by the reduced flavins, flavine adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which are bound in stoichiometrical amounts to the enzyme. NO synthase shows similarities to cytochrome P450 (cytochrome c) reductase, another FAD- and FMN-containing enzyme, and we found that NO synthase reduced cytochromes and artificial, low molecular mass electron acceptors in a superoxide dismutase-insensitive manner. Thus, NO synthase apparently represents a Ca(2+)-regulated, soluble isoform of cytochrome P450 reductase.", "contents": "Nitric oxide synthase-catalyzed activation of oxygen and reduction of cytochromes: reaction mechanisms and possible physiological implications. Purified cerebellar nitric oxide (NO) synthase was found to reduce molecular oxygen to hydrogen peroxide at low concentrations of its substrate L-arginine or its cofactor tetrahydrobiopterin. The characteristics of oxygen reduction appeared to be similar to NO synthesis, as both reactions required reduced nicotinamide adenine dinucleotide phosphate (NADPH), were dependent on Ca2+/calmodulin, and showed optimal reaction rates at slightly acidic conditions. The electron transport from NADPH to molecular oxygen is probably mediated by the reduced flavins, flavine adenine dinucleotide (FAD) and flavin mononucleotide (FMN), which are bound in stoichiometrical amounts to the enzyme. NO synthase shows similarities to cytochrome P450 (cytochrome c) reductase, another FAD- and FMN-containing enzyme, and we found that NO synthase reduced cytochromes and artificial, low molecular mass electron acceptors in a superoxide dismutase-insensitive manner. Thus, NO synthase apparently represents a Ca(2+)-regulated, soluble isoform of cytochrome P450 reductase."} {"id": "PMID:1282987", "title": "Mechanisms of the endothelium-dependent relaxation induced by NG-hydroxy-L-arginine.", "content": "There are three mechanisms by which NG-hydroxy-L-arginine (L-HOArg) induces endothelium-dependent relaxations. L-HOArg is a substrate for the constitutive nitric oxide (NO) synthase present in endothelial cells (ECs). It reacts with NO released from EC to form a potent and more stable vasodilator. Moreover, it induces a relatively stable, EC-dependent relaxation that is not blocked by the inhibitors of NO synthesis. Subsequently, we have investigated the effects of hydroxyguanidine (HOG) on the biological activity of endothelium-derived relaxing factor (EDRF). HOG potentiated the relaxant responses of rabbit aortic strips to EDRF released from EC by adenosine diphosphate (ADP) or bradykinin as well as those induced by authentic NO. Importantly, it was not a substrate for NO synthesis and it did not affect the generation of prostacyclin by ECs. Thus, the effects of HOG were due to the chemical reaction of HOG with NO released from ECs and the formation of a more stable vasodilator. Moreover, HOG augmented not only agonist-triggered, but also flow-induced, EC-dependent relaxation and both effects of HOG were abolished by NG-nitro-L-arginine methyl ester (L-NO2-Arg). In contrast, the EC-dependent relaxation induced by L-HOArg was not inhibited by L-NO2Arg. Moreover, it was not affected by the removal of extracellular Ca2+, but was blocked by oxyhemoglobin and potentiated by superoxide dismutase. These results demonstrate the involvement of the hydroxyguanidino moiety of L-HOArg in its reaction with NO. Moreover, they strongly support the notion that nitrix oxide mediates both the agonist-triggered and flow-induced endothelium-dependent relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Mechanisms of the endothelium-dependent relaxation induced by NG-hydroxy-L-arginine. There are three mechanisms by which NG-hydroxy-L-arginine (L-HOArg) induces endothelium-dependent relaxations. L-HOArg is a substrate for the constitutive nitric oxide (NO) synthase present in endothelial cells (ECs). It reacts with NO released from EC to form a potent and more stable vasodilator. Moreover, it induces a relatively stable, EC-dependent relaxation that is not blocked by the inhibitors of NO synthesis. Subsequently, we have investigated the effects of hydroxyguanidine (HOG) on the biological activity of endothelium-derived relaxing factor (EDRF). HOG potentiated the relaxant responses of rabbit aortic strips to EDRF released from EC by adenosine diphosphate (ADP) or bradykinin as well as those induced by authentic NO. Importantly, it was not a substrate for NO synthesis and it did not affect the generation of prostacyclin by ECs. Thus, the effects of HOG were due to the chemical reaction of HOG with NO released from ECs and the formation of a more stable vasodilator. Moreover, HOG augmented not only agonist-triggered, but also flow-induced, EC-dependent relaxation and both effects of HOG were abolished by NG-nitro-L-arginine methyl ester (L-NO2-Arg). In contrast, the EC-dependent relaxation induced by L-HOArg was not inhibited by L-NO2Arg. Moreover, it was not affected by the removal of extracellular Ca2+, but was blocked by oxyhemoglobin and potentiated by superoxide dismutase. These results demonstrate the involvement of the hydroxyguanidino moiety of L-HOArg in its reaction with NO. Moreover, they strongly support the notion that nitrix oxide mediates both the agonist-triggered and flow-induced endothelium-dependent relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1282988", "title": "Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis.", "content": "Nitric oxide (NO) is a widespread biological mediator with myriad functions. We have demonstrated that methylated arginines capable of inhibiting NO synthesis circulate in the plasma of healthy volunteers and are excreted unchanged in the urine. Up to 10 mg of asymmetric dimethylarginine is excreted in the urine every day, and this compound inhibits NO synthesis in vitro and in vivo, in animals and in humans. This finding raises the possibility that these compounds may act as endogenous regulators of the L-arginine:NO pathway in health and disease.", "contents": "Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. Nitric oxide (NO) is a widespread biological mediator with myriad functions. We have demonstrated that methylated arginines capable of inhibiting NO synthesis circulate in the plasma of healthy volunteers and are excreted unchanged in the urine. Up to 10 mg of asymmetric dimethylarginine is excreted in the urine every day, and this compound inhibits NO synthesis in vitro and in vivo, in animals and in humans. This finding raises the possibility that these compounds may act as endogenous regulators of the L-arginine:NO pathway in health and disease."} {"id": "PMID:1282989", "title": "Ultraviolet-irradiated human endothelial cells elaborate nitric oxide that may evoke vasodilatory response.", "content": "Human skin absorbs solar ultraviolet radiation which evokes vasodilation by a mechanism that is unknown. In this work, we show that ultraviolet (290-320 nm) irradiation of cultured human endothelial cells with doses (60 mJ/cm2) evoked nitric oxide (NO) release that was sustained for more than 60 min. In addition to augmenting NO, cyclic GMP production by human endothelial cells was also increased in a time-dependent manner. Ultraviolet stimulation of NO production was also observed with the enzyme NO synthase purified from the cytosol of human endothelial cells. These results indicate that ultraviolet radiation stimulates NO release, which stimulates cyclic GMP production by vascular smooth muscle, which results in a relaxation response.", "contents": "Ultraviolet-irradiated human endothelial cells elaborate nitric oxide that may evoke vasodilatory response. Human skin absorbs solar ultraviolet radiation which evokes vasodilation by a mechanism that is unknown. In this work, we show that ultraviolet (290-320 nm) irradiation of cultured human endothelial cells with doses (60 mJ/cm2) evoked nitric oxide (NO) release that was sustained for more than 60 min. In addition to augmenting NO, cyclic GMP production by human endothelial cells was also increased in a time-dependent manner. Ultraviolet stimulation of NO production was also observed with the enzyme NO synthase purified from the cytosol of human endothelial cells. These results indicate that ultraviolet radiation stimulates NO release, which stimulates cyclic GMP production by vascular smooth muscle, which results in a relaxation response."} {"id": "PMID:1282990", "title": "New method of investigating functional roles of pressure-sensitive mechanoreceptor in human endothelial cells.", "content": "The role of pressure-sensitive mechanoreceptors (PSMRs) in histamine-stimulated nitric oxide release from cultured human endothelial cells was investigated, using our new method (helium pack method). PSMRs were stimulated by various levels of pressure applied in addition to atmospheric pressure (40, 80, 120, and 160 mm Hg). Histamine-stimulated nitric oxide release was inhibited in a pressure-dependent manner. Our results suggest that PSMRs modulate nitric oxide release from endothelial cells.", "contents": "New method of investigating functional roles of pressure-sensitive mechanoreceptor in human endothelial cells. The role of pressure-sensitive mechanoreceptors (PSMRs) in histamine-stimulated nitric oxide release from cultured human endothelial cells was investigated, using our new method (helium pack method). PSMRs were stimulated by various levels of pressure applied in addition to atmospheric pressure (40, 80, 120, and 160 mm Hg). Histamine-stimulated nitric oxide release was inhibited in a pressure-dependent manner. Our results suggest that PSMRs modulate nitric oxide release from endothelial cells."} {"id": "PMID:1282991", "title": "Endogenous nitric oxide modulates sympathetic neuroeffector transmission in the isolated rabbit lateral saphenous vein.", "content": "The rabbit isolated lateral saphenous vein (RLSV) has a heterogeneous population of alpha-adrenoceptors. Responses to electrical field stimulation, in the presence of cocaine, exhibit both alpha 1- and alpha 2-adrenoceptor-mediated components. The present study examined sympathetic neuroeffector transmission and the response to exogenous catecholamines after inhibition of nitric oxide (NO) synthesis with N omega-nitro-L-arginine methyl ester (L-NAME). A comparison of the response in the presence and absence of a functional endothelium was also carried out. L-NAME potentiated the first and second components of the response to nerve stimulation on the order of 300 and 500%, respectively. L-NAME also significantly potentiated responses to norepinephrine (NE), phenylephrine (PE), and UK 14304. Selective antagonism of the first phase was seen with prazosin (alpha 1-antagonist, 0.1 microM) and the second phase with rauwolscine (alpha 2-antagonist, 1 microM). In the presence of L-NAME, the remaining (uninhibited) components were potentiated. Removal of endothelial function induced by gentle rubbing of the intimal surface abolished potentiation to exogenous NE, PE, and UK14304 by L-NAME. However, a significant degree of potentiation of the neurogenic response was observed in the rubbed tissues in response to L-NAME. This suggests that there may be a nonendothelial source of NO that can modulate the neurogenic response to electrical field stimulation.", "contents": "Endogenous nitric oxide modulates sympathetic neuroeffector transmission in the isolated rabbit lateral saphenous vein. The rabbit isolated lateral saphenous vein (RLSV) has a heterogeneous population of alpha-adrenoceptors. Responses to electrical field stimulation, in the presence of cocaine, exhibit both alpha 1- and alpha 2-adrenoceptor-mediated components. The present study examined sympathetic neuroeffector transmission and the response to exogenous catecholamines after inhibition of nitric oxide (NO) synthesis with N omega-nitro-L-arginine methyl ester (L-NAME). A comparison of the response in the presence and absence of a functional endothelium was also carried out. L-NAME potentiated the first and second components of the response to nerve stimulation on the order of 300 and 500%, respectively. L-NAME also significantly potentiated responses to norepinephrine (NE), phenylephrine (PE), and UK 14304. Selective antagonism of the first phase was seen with prazosin (alpha 1-antagonist, 0.1 microM) and the second phase with rauwolscine (alpha 2-antagonist, 1 microM). In the presence of L-NAME, the remaining (uninhibited) components were potentiated. Removal of endothelial function induced by gentle rubbing of the intimal surface abolished potentiation to exogenous NE, PE, and UK14304 by L-NAME. However, a significant degree of potentiation of the neurogenic response was observed in the rubbed tissues in response to L-NAME. This suggests that there may be a nonendothelial source of NO that can modulate the neurogenic response to electrical field stimulation."} {"id": "PMID:1282992", "title": "Effect of nitric oxide on membrane potential and contraction of rat aorta.", "content": "Influence of nitric oxide (NO) on the membrane potential of rat aorta was assessed by blocking endothelial NO synthase with N omega-nitro-L-arginine (NOArg). Membrane potential was measured by two different methods: intracellular microelectrodes and [3H]tetraphenylphosphonium bromide ([3H]TPP+) uptake. Blocking of NO synthesis with NOArg (10(-4) M) depolarized the membrane by 4-6 mV. The NOArg-induced depolarization was suppressed by the NO donor SIN-1 (10(-5) M). Incubation with NOArg (10(-4) M) decreased the basal level of cGMP, and increased the basal 45Ca2+ influx as well as the sensitivity of contractile response to KCl. Results indicate that NO released by endothelial cells permanently hyperpolarizes the membrane of rat aorta smooth muscle cells and thereby may control the opening of voltage-dependent Ca2+ channels.", "contents": "Effect of nitric oxide on membrane potential and contraction of rat aorta. Influence of nitric oxide (NO) on the membrane potential of rat aorta was assessed by blocking endothelial NO synthase with N omega-nitro-L-arginine (NOArg). Membrane potential was measured by two different methods: intracellular microelectrodes and [3H]tetraphenylphosphonium bromide ([3H]TPP+) uptake. Blocking of NO synthesis with NOArg (10(-4) M) depolarized the membrane by 4-6 mV. The NOArg-induced depolarization was suppressed by the NO donor SIN-1 (10(-5) M). Incubation with NOArg (10(-4) M) decreased the basal level of cGMP, and increased the basal 45Ca2+ influx as well as the sensitivity of contractile response to KCl. Results indicate that NO released by endothelial cells permanently hyperpolarizes the membrane of rat aorta smooth muscle cells and thereby may control the opening of voltage-dependent Ca2+ channels."} {"id": "PMID:1282993", "title": "Histochemistry of guanylate cyclase, phosphodiesterase, and NADPH-diaphorase (nitric oxide synthase) in rat brain vasculature.", "content": "The distribution of guanylate cyclase, phosphodiesterase, and NADPH-diaphorase [nitric oxide (NO) synthase] was studied in rat brain both at the light and electron microscopic level with special emphasis on the vascular system. We showed that the cGMP-generating enzyme is located in cells (glial cells and pericytes) surrounding cerebral vessels, but not in the endothelium. For NO synthase, a dual localization was observed. The enzyme is present in parts of the endothelium and in nerve endings apparently innervating larger brain vessels. We propose, therefore, that NO acts on guanylate cyclase both from a \"synaptic\" and endothelial source.", "contents": "Histochemistry of guanylate cyclase, phosphodiesterase, and NADPH-diaphorase (nitric oxide synthase) in rat brain vasculature. The distribution of guanylate cyclase, phosphodiesterase, and NADPH-diaphorase [nitric oxide (NO) synthase] was studied in rat brain both at the light and electron microscopic level with special emphasis on the vascular system. We showed that the cGMP-generating enzyme is located in cells (glial cells and pericytes) surrounding cerebral vessels, but not in the endothelium. For NO synthase, a dual localization was observed. The enzyme is present in parts of the endothelium and in nerve endings apparently innervating larger brain vessels. We propose, therefore, that NO acts on guanylate cyclase both from a \"synaptic\" and endothelial source."} {"id": "PMID:1282994", "title": "Structure of the bovine endothelin-B receptor gene and its tissue-specific expression revealed by northern analysis.", "content": "We have isolated and characterized the gene encoding the bovine endothelin (ET) receptor ETB with seven putative membrane-spanning domains. The gene exists as a single copy of the bovine genome and extends over 36 kilobases. The coding region is divided into seven exons separated by six introns; the first exon encodes the first and second transmembrane domains and each of the following transmembrane domains is encoded by a separate exon. The 5' region of the transcript was examined by the ribonuclease protection analysis; multiple start sites were deduced with no apparent \"TATA\" box in the expected upstream region. Northern blot analysis demonstrated a widespread but tissue-specific distribution of the ETB receptor in bovine tissues.", "contents": "Structure of the bovine endothelin-B receptor gene and its tissue-specific expression revealed by northern analysis. We have isolated and characterized the gene encoding the bovine endothelin (ET) receptor ETB with seven putative membrane-spanning domains. The gene exists as a single copy of the bovine genome and extends over 36 kilobases. The coding region is divided into seven exons separated by six introns; the first exon encodes the first and second transmembrane domains and each of the following transmembrane domains is encoded by a separate exon. The 5' region of the transcript was examined by the ribonuclease protection analysis; multiple start sites were deduced with no apparent \"TATA\" box in the expected upstream region. Northern blot analysis demonstrated a widespread but tissue-specific distribution of the ETB receptor in bovine tissues."} {"id": "PMID:1282995", "title": "Effects of storage solutions on contraction and relaxation of isolated saphenous veins.", "content": "Saphenous veins are placed frequently in storage solutions before use as coronary bypass grafts. Controversy remains regarding which solution is optimal for the preservation of endothelium and vascular smooth muscle viability. Thus, this study measured the effect of four different storage solutions on saphenous vein smooth muscle and endothelial cell function. Saphenous vein segments from five baboons were stored for 3 h in one of four storage solutions consisting of physiological salt solution (PSS), University of Wisconsin solution (UWS), normal saline solution (NSS), or autologous whole blood (WB). Following storage, veins were suspended for isometric tension recording in tissue baths filled with PSS. Veins stored in PSS, UWS, and NSS showed similar contractile amplitude and agonist sensitivity to norepinephrine (10(-8) -10(-4) M) and KCl (20-100 mM). However, veins stored in WB contracted 31% less to KCl on average than those stored in the other three solutions (p < 0.05). The direct vascular muscle vasodilator, papaverine (10(-7) -10(-4) M), and the endothelium-dependent dilator, A23187 (10(-5) M), relaxed all vein preparations equally well. These results suggest that after storage in PSS, UWS, and NSS, contractile and relaxant vascular responses are similar in isolated saphenous veins. However, although veins stored in WB show comparable relaxation responses, they demonstrate an impaired vascular contraction immediately after storage. We conclude that storage of veins in blood may immediately modify vascular smooth muscle function.", "contents": "Effects of storage solutions on contraction and relaxation of isolated saphenous veins. Saphenous veins are placed frequently in storage solutions before use as coronary bypass grafts. Controversy remains regarding which solution is optimal for the preservation of endothelium and vascular smooth muscle viability. Thus, this study measured the effect of four different storage solutions on saphenous vein smooth muscle and endothelial cell function. Saphenous vein segments from five baboons were stored for 3 h in one of four storage solutions consisting of physiological salt solution (PSS), University of Wisconsin solution (UWS), normal saline solution (NSS), or autologous whole blood (WB). Following storage, veins were suspended for isometric tension recording in tissue baths filled with PSS. Veins stored in PSS, UWS, and NSS showed similar contractile amplitude and agonist sensitivity to norepinephrine (10(-8) -10(-4) M) and KCl (20-100 mM). However, veins stored in WB contracted 31% less to KCl on average than those stored in the other three solutions (p < 0.05). The direct vascular muscle vasodilator, papaverine (10(-7) -10(-4) M), and the endothelium-dependent dilator, A23187 (10(-5) M), relaxed all vein preparations equally well. These results suggest that after storage in PSS, UWS, and NSS, contractile and relaxant vascular responses are similar in isolated saphenous veins. However, although veins stored in WB show comparable relaxation responses, they demonstrate an impaired vascular contraction immediately after storage. We conclude that storage of veins in blood may immediately modify vascular smooth muscle function."} {"id": "PMID:1282996", "title": "Endothelium-dependent effects of platelet-activating factor in the coronary circulation.", "content": "In experiments on anesthetized dogs, the effect of intracoronary administration of different doses of platelet-activating factor (PAF) has been investigated. One of the branches of the left coronary artery was catheterized via the main carotid artery. The coronary artery was autoperfused with blood from the subclavian artery. Intracoronary administration of small doses of PAF (100 and 200 ng/kg) caused a dose-dependent decrease in coronary resistance (CR) and an increase in coronary blood flow (CF). When 200 ng/kg of PAF was used, these changes were 30 and 34% vs. control, respectively. Dose increase to 300 ng/kg led to a biphasic reaction. Intracoronary administration of larger PAF doses produced opposite effects, i.e., increase in CR and decrease in CF. Chemical de-endothelialization by saponin (5 mg/5 ml, 1.5-2 min) transformed coronary dilation to small doses of PAF to constriction. The CR rose from 2.8 +/- 0.3 to 5.6 +/- 0.9 mm Hg/ml/min (p < 0.01) and CF dropped two-fold. The PAF receptor antagonists BN 52021 (6 mg/kg) and WEB 2086 (3 mg/kg) completely abolished PAF-induced coronary reactions. Hence, PAF-induced vasodilation of the canine coronary circulation is endothelium dependent.", "contents": "Endothelium-dependent effects of platelet-activating factor in the coronary circulation. In experiments on anesthetized dogs, the effect of intracoronary administration of different doses of platelet-activating factor (PAF) has been investigated. One of the branches of the left coronary artery was catheterized via the main carotid artery. The coronary artery was autoperfused with blood from the subclavian artery. Intracoronary administration of small doses of PAF (100 and 200 ng/kg) caused a dose-dependent decrease in coronary resistance (CR) and an increase in coronary blood flow (CF). When 200 ng/kg of PAF was used, these changes were 30 and 34% vs. control, respectively. Dose increase to 300 ng/kg led to a biphasic reaction. Intracoronary administration of larger PAF doses produced opposite effects, i.e., increase in CR and decrease in CF. Chemical de-endothelialization by saponin (5 mg/5 ml, 1.5-2 min) transformed coronary dilation to small doses of PAF to constriction. The CR rose from 2.8 +/- 0.3 to 5.6 +/- 0.9 mm Hg/ml/min (p < 0.01) and CF dropped two-fold. The PAF receptor antagonists BN 52021 (6 mg/kg) and WEB 2086 (3 mg/kg) completely abolished PAF-induced coronary reactions. Hence, PAF-induced vasodilation of the canine coronary circulation is endothelium dependent."} {"id": "PMID:1282997", "title": "Involvement of endothelium in vasodilating effects of vintoperol.", "content": "Experiments were performed on vessels of the femoral vascular bed of anesthetized dogs and on isolated rings of the rat pulmonary artery, vena cava, and thoracic aorta. Vintoperol was administered intra-arterially (0.01, 0.1, and 0.3 mg/kg/min for 10 min) or added in vitro (10(-4) M). De-endothelialization by saponin (0.5 mg/ml for 5 min) of intact vascular beds or mechanical endothelium removal in rings decreased vasodilation or relaxation by 50-60% vs. control. In de-endothelialized vascular beds, vintoperol (0.3 mg/kg/min) increased blood flow by 18 +/- 5% but 47 +/- 4% under control conditions (p < 0.05). Methylene blue (10 mg/kg) reduced the increment of blood flow to vintoperol from 47 +/- 4 to 24 +/- 4% (p < 0.05). After de-endothelialization of the isolated pulmonary artery, relaxation of precontracted segments was reduced (21 +/- 4% vs. 56 +/- 5% under control conditions; p < 0.05). Vintoperol-induced relaxation of vascular rings was also inhibited by gossypol (2 x 10(-5) M) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) depended on the duration of exposure to the inhibitors. In conclusion, relaxation to vintoperol must be mediated by the release of endothelium-derived nitric oxide.", "contents": "Involvement of endothelium in vasodilating effects of vintoperol. Experiments were performed on vessels of the femoral vascular bed of anesthetized dogs and on isolated rings of the rat pulmonary artery, vena cava, and thoracic aorta. Vintoperol was administered intra-arterially (0.01, 0.1, and 0.3 mg/kg/min for 10 min) or added in vitro (10(-4) M). De-endothelialization by saponin (0.5 mg/ml for 5 min) of intact vascular beds or mechanical endothelium removal in rings decreased vasodilation or relaxation by 50-60% vs. control. In de-endothelialized vascular beds, vintoperol (0.3 mg/kg/min) increased blood flow by 18 +/- 5% but 47 +/- 4% under control conditions (p < 0.05). Methylene blue (10 mg/kg) reduced the increment of blood flow to vintoperol from 47 +/- 4 to 24 +/- 4% (p < 0.05). After de-endothelialization of the isolated pulmonary artery, relaxation of precontracted segments was reduced (21 +/- 4% vs. 56 +/- 5% under control conditions; p < 0.05). Vintoperol-induced relaxation of vascular rings was also inhibited by gossypol (2 x 10(-5) M) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) or methylene blue (5 x 10(-5) M); the level of inhibition (50-100%) depended on the duration of exposure to the inhibitors. In conclusion, relaxation to vintoperol must be mediated by the release of endothelium-derived nitric oxide."} {"id": "PMID:1282998", "title": "Function of vasoactive factors in the cerebral microcirculation.", "content": "The properties of brain capillary endothelial cells (BCECs) have been analyzed. BCECs express two types of receptor sites for endothelins (ETs), and ETA-like receptor, and an ETB-like receptor that is not coupled to phospholipase C but whose occupancy activates Na+/H+ exchange activity. The ETA receptor is positively coupled to phospholipase C and negatively coupled to adenylate cyclase. BCECs, unlike aortic endothelial cells, express high-affinity receptor sites for C-type natriuretic peptide. They respond to exogenous nitric oxide (NO) and to NO donor molecules by large activations of soluble guanylate cyclase. They produce little cGMP in response to A23187 or to agonists of phospholipase C but do so after an exposure to interleukin-1. The physiological consequence of the high reactivity of BCECs to vasoactive factors is discussed.", "contents": "Function of vasoactive factors in the cerebral microcirculation. The properties of brain capillary endothelial cells (BCECs) have been analyzed. BCECs express two types of receptor sites for endothelins (ETs), and ETA-like receptor, and an ETB-like receptor that is not coupled to phospholipase C but whose occupancy activates Na+/H+ exchange activity. The ETA receptor is positively coupled to phospholipase C and negatively coupled to adenylate cyclase. BCECs, unlike aortic endothelial cells, express high-affinity receptor sites for C-type natriuretic peptide. They respond to exogenous nitric oxide (NO) and to NO donor molecules by large activations of soluble guanylate cyclase. They produce little cGMP in response to A23187 or to agonists of phospholipase C but do so after an exposure to interleukin-1. The physiological consequence of the high reactivity of BCECs to vasoactive factors is discussed."} {"id": "PMID:1282999", "title": "Sustained hyperpolarization of cultured guinea pig coronary endothelial cells induced by adenosine.", "content": "Electrophysiological experiments on cultured monolayers of guinea pig coronary endothelial cells were performed to substantiate the hypothesis that variation of the endothelial membrane potential may be a functionally important mechanism that contributes to the regulation of coronary blood flow. The endothelial cells were loaded with sodium by superfusion with K(+)-free solution at 37 degrees C for 5-30 min. Readmission of external K+ produced a transient hyperpolarization of up to 85 mV, which was due to stimulation of the electrogenic pump current. In most but not all of the monolayers, superfusion with 2 microM adenosine elicited a transient or a sustained hyperpolarization. The transient hyperpolarization had an amplitude of 15 +/- 6 mV. The sustained hyperpolarization had an amplitude of 11 +/- 3 mV. Our results are in line with the hypothesis that the hyperpolarization of the endothelium induced by release of adenosine into the perivascular space of the capillaries may be conducted electronically to the terminal arterioles and may cause vasodilation via current flow through myoendothelial gap junctions.", "contents": "Sustained hyperpolarization of cultured guinea pig coronary endothelial cells induced by adenosine. Electrophysiological experiments on cultured monolayers of guinea pig coronary endothelial cells were performed to substantiate the hypothesis that variation of the endothelial membrane potential may be a functionally important mechanism that contributes to the regulation of coronary blood flow. The endothelial cells were loaded with sodium by superfusion with K(+)-free solution at 37 degrees C for 5-30 min. Readmission of external K+ produced a transient hyperpolarization of up to 85 mV, which was due to stimulation of the electrogenic pump current. In most but not all of the monolayers, superfusion with 2 microM adenosine elicited a transient or a sustained hyperpolarization. The transient hyperpolarization had an amplitude of 15 +/- 6 mV. The sustained hyperpolarization had an amplitude of 11 +/- 3 mV. Our results are in line with the hypothesis that the hyperpolarization of the endothelium induced by release of adenosine into the perivascular space of the capillaries may be conducted electronically to the terminal arterioles and may cause vasodilation via current flow through myoendothelial gap junctions."} {"id": "PMID:1283000", "title": "Purification of Aeromonas hydrophila major outer-membrane proteins: N-terminal sequence analysis and channel-forming properties.", "content": "Four outer-membrane proteins of Aeromonas hydrophila were purified and their N-terminal sequences and channel-forming properties were determined. Three could be matched with proteins from other species. One was a maltoporin, as its level increased when cells were grown in maltose-containing media, and the channel it formed was blocked by maltose. Another was like OmpF and OmpC of Escherichia coli, except that its channel fluctuated much more rapidly. The third protein, which was produced in low-phosphate medium, exhibited several properties of the general anion porin PhoE. The fourth showed no similarity to any known proteins. It had a unique N-terminus and it formed small sharply-defined cation-selective channels. Two other proteins which corresponded to OmpW of Vibrio cholerae and E. coli OmpA were partly characterized.", "contents": "Purification of Aeromonas hydrophila major outer-membrane proteins: N-terminal sequence analysis and channel-forming properties. Four outer-membrane proteins of Aeromonas hydrophila were purified and their N-terminal sequences and channel-forming properties were determined. Three could be matched with proteins from other species. One was a maltoporin, as its level increased when cells were grown in maltose-containing media, and the channel it formed was blocked by maltose. Another was like OmpF and OmpC of Escherichia coli, except that its channel fluctuated much more rapidly. The third protein, which was produced in low-phosphate medium, exhibited several properties of the general anion porin PhoE. The fourth showed no similarity to any known proteins. It had a unique N-terminus and it formed small sharply-defined cation-selective channels. Two other proteins which corresponded to OmpW of Vibrio cholerae and E. coli OmpA were partly characterized."} {"id": "PMID:1283001", "title": "The effect of ribosomal protein S1 from Escherichia coli and Micrococcus luteus on protein synthesis in vitro by E. coli and Bacillus subtilis.", "content": "We have designed a set of nine plasmids containing the Bacillus pumilis cat gene with one of three Shine-Dalgarno (SD) sequences (weak, strong or stronger) and one of three initiation codons (AUG, GUG or UUG). These constructions have been used to determine the effect of ribosomal protein S1, SD and initiation codon sequences and Escherichia coli ribosomal protein S1 on translation in vitro by E. coli and B. subtilis ribosomes. Translation of these nine constructions was determined with three types of ribosomes: E. coli containing ribosomal protein S1, E. coli depleted of S1, and B. subtilis which is naturally free of S1. E. coli ribosomes were able to translate all nine transcripts with variable efficiencies. B. subtilis and S1-depleted E. coli ribosomes were similar to each other and differed from non-depleted E. coli ribosomes in that they required strong or stronger SD sequences and were unable to translate any of the weak transcripts. Addition of S1 from either E. coli or Micrococcus luteus, a Gram-positive bacterium, enabled S1-depleted E. coli ribosomes to translate mRNAs with weak SD sequences but had no effect on B. subtilis ribosomes. AUG was the preferred initiation codon for all ribosome types; however, B. subtilis ribosomes showed greater tolerance for the non-AUG codons than either type of E. coli ribosome. The presence of a strong or stronger SD sequence increased the efficiency by which E. coli ribosomes could utilize non-AUG codons.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "The effect of ribosomal protein S1 from Escherichia coli and Micrococcus luteus on protein synthesis in vitro by E. coli and Bacillus subtilis. We have designed a set of nine plasmids containing the Bacillus pumilis cat gene with one of three Shine-Dalgarno (SD) sequences (weak, strong or stronger) and one of three initiation codons (AUG, GUG or UUG). These constructions have been used to determine the effect of ribosomal protein S1, SD and initiation codon sequences and Escherichia coli ribosomal protein S1 on translation in vitro by E. coli and B. subtilis ribosomes. Translation of these nine constructions was determined with three types of ribosomes: E. coli containing ribosomal protein S1, E. coli depleted of S1, and B. subtilis which is naturally free of S1. E. coli ribosomes were able to translate all nine transcripts with variable efficiencies. B. subtilis and S1-depleted E. coli ribosomes were similar to each other and differed from non-depleted E. coli ribosomes in that they required strong or stronger SD sequences and were unable to translate any of the weak transcripts. Addition of S1 from either E. coli or Micrococcus luteus, a Gram-positive bacterium, enabled S1-depleted E. coli ribosomes to translate mRNAs with weak SD sequences but had no effect on B. subtilis ribosomes. AUG was the preferred initiation codon for all ribosome types; however, B. subtilis ribosomes showed greater tolerance for the non-AUG codons than either type of E. coli ribosome. The presence of a strong or stronger SD sequence increased the efficiency by which E. coli ribosomes could utilize non-AUG codons.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283002", "title": "High copy number of the pUC plasmid results from a Rom/Rop-suppressible point mutation in RNA II.", "content": "The plasmids pUC18 and pUC19 are pBR322 derivatives that replicate at a copy number several fold higher than the parent during growth of Escherichia coli at 37 degrees C. We show here that the high copy number of pUC plasmids results from a single point mutation in the replication primer, RNA II, and that the phenotypic effects of this mutation can be suppressed by the Rom (RNA one modulator)/Rop protein or by lowering the growth temperature to 30 degrees C. The mutation's effects are enhanced by cell growth at 42 degrees C, at which copy number is further increased. During normal cell growth, the pUC mutation does not affect the length or function of RNA I, the antisense repressor of plasmid DNA replication, but may, as computer analysis suggests, alter the secondary structure of pUC RNA II. We suggest that the pUC mutation impedes interactions between the repressor and the primer by producing a temperature-dependent alteration of the RNA II conformation. The Rom/Rop protein may either promote normal folding of the mutated RNA II or, alternatively, may enable the interaction of sub-optimally folded RNA II with the repressor.", "contents": "High copy number of the pUC plasmid results from a Rom/Rop-suppressible point mutation in RNA II. The plasmids pUC18 and pUC19 are pBR322 derivatives that replicate at a copy number several fold higher than the parent during growth of Escherichia coli at 37 degrees C. We show here that the high copy number of pUC plasmids results from a single point mutation in the replication primer, RNA II, and that the phenotypic effects of this mutation can be suppressed by the Rom (RNA one modulator)/Rop protein or by lowering the growth temperature to 30 degrees C. The mutation's effects are enhanced by cell growth at 42 degrees C, at which copy number is further increased. During normal cell growth, the pUC mutation does not affect the length or function of RNA I, the antisense repressor of plasmid DNA replication, but may, as computer analysis suggests, alter the secondary structure of pUC RNA II. We suggest that the pUC mutation impedes interactions between the repressor and the primer by producing a temperature-dependent alteration of the RNA II conformation. The Rom/Rop protein may either promote normal folding of the mutated RNA II or, alternatively, may enable the interaction of sub-optimally folded RNA II with the repressor."} {"id": "PMID:1283003", "title": "An ELISA-like assay for hyaluronidase and hyaluronidase inhibitors.", "content": "Hyaluronic acid (HA) is a prominent molecule in the extracellular matrix and is enriched whenever there is rapid tissue proliferation, regeneration and repair. HA is degraded in part by hyaluronidases (HA'ases) that are not well characterized. We have developed a novel ELISA-like rapid assay for HA'ases and their inhibitors. The assay is based on a high affinity biotinylated HA-binding peptide derived from tryptic digests of proteoglycan core protein of bovine nasal cartilage and the avidin-biotin reaction. HA-coated plates were incubated with serial dilutions of Streptomyces HA'ase, and the undegraded HA was measured. This established a standard curve for HA'ase activity against which all unknown enzyme samples were compared. The assay is easily modified to also serve a measure of HA'ase inhibitors. For detection of inhibitors, aliquots of sample were preincubated with a known activity of HA'ase and inhibition of HA degradation by the mixture was measured. We have used this assay to document the presence of potent HA'ase inhibitors in fetal calf sera. These techniques will aid in the purification and characterization of Ha'ases and their inhibitors.", "contents": "An ELISA-like assay for hyaluronidase and hyaluronidase inhibitors. Hyaluronic acid (HA) is a prominent molecule in the extracellular matrix and is enriched whenever there is rapid tissue proliferation, regeneration and repair. HA is degraded in part by hyaluronidases (HA'ases) that are not well characterized. We have developed a novel ELISA-like rapid assay for HA'ases and their inhibitors. The assay is based on a high affinity biotinylated HA-binding peptide derived from tryptic digests of proteoglycan core protein of bovine nasal cartilage and the avidin-biotin reaction. HA-coated plates were incubated with serial dilutions of Streptomyces HA'ase, and the undegraded HA was measured. This established a standard curve for HA'ase activity against which all unknown enzyme samples were compared. The assay is easily modified to also serve a measure of HA'ase inhibitors. For detection of inhibitors, aliquots of sample were preincubated with a known activity of HA'ase and inhibition of HA degradation by the mixture was measured. We have used this assay to document the presence of potent HA'ase inhibitors in fetal calf sera. These techniques will aid in the purification and characterization of Ha'ases and their inhibitors."} {"id": "PMID:1283004", "title": "Recognition of Entamoeba histolytica lipophosphoglycan by a strain-specific monoclonal antibody and human immune sera.", "content": "Western blot analysis showed that the monoclonal antibody 2D7.10 recognized lipophosphoglycan (LPG) from Entamoeba histolytica HM-1:IMSS. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) pattern of [3H]galactose-labeled LPG and Western blot analysis of total lysate of E. histolytica with 2D7.10 revealed patterns similar to that of LPG with 2D7.10. This antibody could also immunoprecipitate purified LPG from the strain HM-1:IMSS after biosynthetically labeling with [3H]galactose and [32P]orthophosphate. However, no immunoprecipitation was observed when 2D7.10 was incubated with [32P]orthophosphate-labeled purified LPG from strain 200:NIH. Sera from patients suffering from invasive amoebiasis also immunoprecipitated 32P-labeled, purified LPG and could immunostain this molecule in Western blots. The human immune sera recognized carbohydrate epitopes but not the associated polypeptides of LPG, as evidenced by sensitivity to periodate digestion, mild acid hydrolysis but not to pronase treatment. It was earlier shown that 2D7.10 binds a carbohydrate epitope in a subset of axenized pathogenic strains of E. histolytica and that this epitope undergoes changes when cultured along with bacteria. These observations suggest that the E. histolytica LPG contains a strain-specific, variable epitope and that LPG is immunogenic in human.", "contents": "Recognition of Entamoeba histolytica lipophosphoglycan by a strain-specific monoclonal antibody and human immune sera. Western blot analysis showed that the monoclonal antibody 2D7.10 recognized lipophosphoglycan (LPG) from Entamoeba histolytica HM-1:IMSS. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) pattern of [3H]galactose-labeled LPG and Western blot analysis of total lysate of E. histolytica with 2D7.10 revealed patterns similar to that of LPG with 2D7.10. This antibody could also immunoprecipitate purified LPG from the strain HM-1:IMSS after biosynthetically labeling with [3H]galactose and [32P]orthophosphate. However, no immunoprecipitation was observed when 2D7.10 was incubated with [32P]orthophosphate-labeled purified LPG from strain 200:NIH. Sera from patients suffering from invasive amoebiasis also immunoprecipitated 32P-labeled, purified LPG and could immunostain this molecule in Western blots. The human immune sera recognized carbohydrate epitopes but not the associated polypeptides of LPG, as evidenced by sensitivity to periodate digestion, mild acid hydrolysis but not to pronase treatment. It was earlier shown that 2D7.10 binds a carbohydrate epitope in a subset of axenized pathogenic strains of E. histolytica and that this epitope undergoes changes when cultured along with bacteria. These observations suggest that the E. histolytica LPG contains a strain-specific, variable epitope and that LPG is immunogenic in human."} {"id": "PMID:1283007", "title": "Differential effect of right and left hemispheric lesions on two memory tasks: free recall of items and recall of spatial location.", "content": "The effect of lateralized cerebral damage on free recall of items and recall of spatial location, under intentional and incidental learning conditions, was investigated. Eleven right brain-damaged (RBD) patients, 10 left brain-damaged (LBD) patients, 14 young and 11 elderly normal controls, participated in this study. The overall performance of the control groups was better than that of the patient groups. For all groups, free recall was better under intentional than under incidental learning condition. On recall of spatial location the learning condition had a differential effect on the groups. The RBD group performed better than the LBD group under intentional learning condition, while the reverse was found under incidental learning condition. The young-control group showed an advantage over the elderly-control group under intentional but not under incidental learning condition. The results are discussed in regard to different approaches to the distinction between automatic and effortful memory processes and their lateralization in the cerebral hemispheres.", "contents": "Differential effect of right and left hemispheric lesions on two memory tasks: free recall of items and recall of spatial location. The effect of lateralized cerebral damage on free recall of items and recall of spatial location, under intentional and incidental learning conditions, was investigated. Eleven right brain-damaged (RBD) patients, 10 left brain-damaged (LBD) patients, 14 young and 11 elderly normal controls, participated in this study. The overall performance of the control groups was better than that of the patient groups. For all groups, free recall was better under intentional than under incidental learning condition. On recall of spatial location the learning condition had a differential effect on the groups. The RBD group performed better than the LBD group under intentional learning condition, while the reverse was found under incidental learning condition. The young-control group showed an advantage over the elderly-control group under intentional but not under incidental learning condition. The results are discussed in regard to different approaches to the distinction between automatic and effortful memory processes and their lateralization in the cerebral hemispheres."} {"id": "PMID:1283005", "title": "[Subacute leukoencephalopathy after radio- and chemotherapy of lymphoblastic lymphoma].", "content": "In a patient aged 34 with lymphoblastic lymphoma lymphomatous infiltrations developed in the leptomeninges but were controlled with radiotherapy and chemotherapy. Recurrence of neurological signs after 7 months was recognized as relapse of lymphoma in the central nervous system, but in the brain extensive demyelination and necrotic changes were found. The authors relate the development of leucoencephalopathy to the hypersensitivity of the nervous tissue to chemotherapy after previous radiotherapy.", "contents": "[Subacute leukoencephalopathy after radio- and chemotherapy of lymphoblastic lymphoma]. In a patient aged 34 with lymphoblastic lymphoma lymphomatous infiltrations developed in the leptomeninges but were controlled with radiotherapy and chemotherapy. Recurrence of neurological signs after 7 months was recognized as relapse of lymphoma in the central nervous system, but in the brain extensive demyelination and necrotic changes were found. The authors relate the development of leucoencephalopathy to the hypersensitivity of the nervous tissue to chemotherapy after previous radiotherapy."} {"id": "PMID:1283008", "title": "Distribution and origin of extrinsic nerve fibers containing calcitonin gene-related peptide, substance P and galanin in the rat upper rectum.", "content": "The distributions of nerve fibers containing calcitonin gene-related peptide (CGRP), substance P (SP) and galanin (GAL) were examined in the rat rectum of mutants rats, aganglionic rats (AGRs), which completely lack the intramural nerve cells in the large intestine, and of their normal littermates. The origin of extrinsic peptide-containing nerve fibers was examined using retrograde tracing combined with immunohistochemistry in normal rats. In the rectum of normal rats, CGRP-, SP- and GAL-immunoreactive varicose fibers were observed throughout all layers of the rectal wall, and immunoreactive nerve cells were present in the enteric ganglia of colchicine-treated rats. In the aganglionic rectum of AGR, a rich supply of CGRP-immunoreactive fibers was observed in the mucosa, around the blood vessels, and in the submucous and intermuscular spaces. SP- and GAL-immunoreactive fibers in the aganglionic rectum showed a similar distribution to CGRP-immunoreactive fibers but were less dense. These results suggest that most of CGRP-positive fibers in the rectum are extrinsic whereas a large part of SP- or GAL-positive fibers are intrinsic. Fluoro-gold injected into the upper rectum of normal rat labelled nerve cells (less than 10% of total ganglion cells) in the lumbar (L1 and L2) and lumbosacral (L6 and S1) dorsal root ganglia. More than half of nerve cells in the dorsal root ganglia (L6 and S1) projecting to the rectum were immunoreactive for CGRP, and less than 10% were immunoreactive for SP or GAL. Comparison of serial sections of the dorsal root ganglion revealed that about half of the CGRP-immunoreactive cells were also positive for SP or GAL. These results indicate that SP- or GAL-positive neurons projecting to the rectum are scarce in the dorsal root ganglia. The present investigation suggests that CGRP-containing nerves are visceral afferents forming a major component of the sensory innervation of the rat rectum, and SP- and GAL-containing nerves which share their extrinsic origins appear to form a lesser proportion of the sensory innervation.", "contents": "Distribution and origin of extrinsic nerve fibers containing calcitonin gene-related peptide, substance P and galanin in the rat upper rectum. The distributions of nerve fibers containing calcitonin gene-related peptide (CGRP), substance P (SP) and galanin (GAL) were examined in the rat rectum of mutants rats, aganglionic rats (AGRs), which completely lack the intramural nerve cells in the large intestine, and of their normal littermates. The origin of extrinsic peptide-containing nerve fibers was examined using retrograde tracing combined with immunohistochemistry in normal rats. In the rectum of normal rats, CGRP-, SP- and GAL-immunoreactive varicose fibers were observed throughout all layers of the rectal wall, and immunoreactive nerve cells were present in the enteric ganglia of colchicine-treated rats. In the aganglionic rectum of AGR, a rich supply of CGRP-immunoreactive fibers was observed in the mucosa, around the blood vessels, and in the submucous and intermuscular spaces. SP- and GAL-immunoreactive fibers in the aganglionic rectum showed a similar distribution to CGRP-immunoreactive fibers but were less dense. These results suggest that most of CGRP-positive fibers in the rectum are extrinsic whereas a large part of SP- or GAL-positive fibers are intrinsic. Fluoro-gold injected into the upper rectum of normal rat labelled nerve cells (less than 10% of total ganglion cells) in the lumbar (L1 and L2) and lumbosacral (L6 and S1) dorsal root ganglia. More than half of nerve cells in the dorsal root ganglia (L6 and S1) projecting to the rectum were immunoreactive for CGRP, and less than 10% were immunoreactive for SP or GAL. Comparison of serial sections of the dorsal root ganglion revealed that about half of the CGRP-immunoreactive cells were also positive for SP or GAL. These results indicate that SP- or GAL-positive neurons projecting to the rectum are scarce in the dorsal root ganglia. The present investigation suggests that CGRP-containing nerves are visceral afferents forming a major component of the sensory innervation of the rat rectum, and SP- and GAL-containing nerves which share their extrinsic origins appear to form a lesser proportion of the sensory innervation."} {"id": "PMID:1283006", "title": "[A rare case of metastasis of Hodgkin's disease to the spinal cord].", "content": "A rare case of Hodgkin's lymphoma metastasis to the spinal cord is reported. The first signs of the metastasis appeared in the 6th year of cytostatic treatment. Diagnostic difficulties hampered causative treatment.", "contents": "[A rare case of metastasis of Hodgkin's disease to the spinal cord]. A rare case of Hodgkin's lymphoma metastasis to the spinal cord is reported. The first signs of the metastasis appeared in the 6th year of cytostatic treatment. Diagnostic difficulties hampered causative treatment."} {"id": "PMID:1283009", "title": "Description of a mechanistic approach to pain management in advanced cancer. Preliminary report.", "content": "A mechanistic approach to advanced cancer pain management is proposed, based on the clinically perceived anatomical and pathophysiological mechanisms of pain generation. It is an extension of the World Health Organisation (WHO) analgesic ladder in which severity of pain is the principal determinant of analgesic choice. The mechanistic categories are: superficial somatic, deep somatic, visceral and neurogenic (mixed or pure, i.e., nociceptive component present or absent). Allocation of pain to the different categories is based on clinical history, physical findings and investigations to establish the site and extent of active primary or metastatic tumor deposits, and evidence of previous response to medication. Drug choice sequence is determined by the dominant pain mechanism judged to be present and not the severity of the pain. In order to describe this approach, mechanisms of pain, disease distribution and drug treatment have been analysed in the first 20 consecutive patients who consented to enter a longitudinal pain description and evaluation study on admission to an inpatient hospice unit. Despite a high exclusion rate from research standard monitoring due to severity of illness and related factors, the majority of eligible patients approached to enter the study did so, and the pain scoring was well tolerated. The implications of this for future research and clinical practice are discussed. In 6 patients only 1 pain mechanism was identified (visceral 4, deep somatic 2). Two mechanisms were present in 8 patients and 3 mechanisms in 6 patients. The deep somatic mechanism was identified in 15 patients, visceral mechanism in 13, neurogenic in 10 and superficial somatic in 2.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Description of a mechanistic approach to pain management in advanced cancer. Preliminary report. A mechanistic approach to advanced cancer pain management is proposed, based on the clinically perceived anatomical and pathophysiological mechanisms of pain generation. It is an extension of the World Health Organisation (WHO) analgesic ladder in which severity of pain is the principal determinant of analgesic choice. The mechanistic categories are: superficial somatic, deep somatic, visceral and neurogenic (mixed or pure, i.e., nociceptive component present or absent). Allocation of pain to the different categories is based on clinical history, physical findings and investigations to establish the site and extent of active primary or metastatic tumor deposits, and evidence of previous response to medication. Drug choice sequence is determined by the dominant pain mechanism judged to be present and not the severity of the pain. In order to describe this approach, mechanisms of pain, disease distribution and drug treatment have been analysed in the first 20 consecutive patients who consented to enter a longitudinal pain description and evaluation study on admission to an inpatient hospice unit. Despite a high exclusion rate from research standard monitoring due to severity of illness and related factors, the majority of eligible patients approached to enter the study did so, and the pain scoring was well tolerated. The implications of this for future research and clinical practice are discussed. In 6 patients only 1 pain mechanism was identified (visceral 4, deep somatic 2). Two mechanisms were present in 8 patients and 3 mechanisms in 6 patients. The deep somatic mechanism was identified in 15 patients, visceral mechanism in 13, neurogenic in 10 and superficial somatic in 2.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283010", "title": "Intrathecal co-administration of substance P and NMDA augments nociceptive responses in the formalin test.", "content": "The effects of intrathecal administration of substance P and N-methyl-D-aspartate (NMDA) were studied in the formalin test in mice. Both substances were administered 5 min before injection of formalin into the hind paw. Co-administration of substance P and NMDA intensified the response in both the 1st (0-10 min) and the 2nd phase (20-30 min) of the formalin test, and increased the duration of the response. The increase in the response to formalin depended on the formalin concentration and was significant with 1% and 5% concentrations of formalin but not with a 0.05% concentration. No increase in the response was observed when NMDA or substance P was given alone. These findings indicate that concurrent activation of spinal NMDA and substance P receptors induces an enhancement of spinal transmission of nociception, and that this enhancement is dependent on the intensity or the quality of the peripheral stimulus.", "contents": "Intrathecal co-administration of substance P and NMDA augments nociceptive responses in the formalin test. The effects of intrathecal administration of substance P and N-methyl-D-aspartate (NMDA) were studied in the formalin test in mice. Both substances were administered 5 min before injection of formalin into the hind paw. Co-administration of substance P and NMDA intensified the response in both the 1st (0-10 min) and the 2nd phase (20-30 min) of the formalin test, and increased the duration of the response. The increase in the response to formalin depended on the formalin concentration and was significant with 1% and 5% concentrations of formalin but not with a 0.05% concentration. No increase in the response was observed when NMDA or substance P was given alone. These findings indicate that concurrent activation of spinal NMDA and substance P receptors induces an enhancement of spinal transmission of nociception, and that this enhancement is dependent on the intensity or the quality of the peripheral stimulus."} {"id": "PMID:1283012", "title": "[Adhesion and mobility of embryonic and tumoral cells].", "content": "Regulation of a number of adhesion molecules during neural crest cell migration was studied. The neural crest, a transient embryonic neural epithelium structure, undergoes mesenchymal transformation (epithelial-mesenchymal transition). The cells then migrate, giving rise to a variety of elements including the peripheral nervous system and melanocytes. During migration, neural crest cells do not express functional cell Adhesion Molecules but interact specifically with cell-binding domains in fibronectin molecules. A rat bladder carcinoma cell line was used as an in vitro model to study conversion of epithelial cells to a migratory fibroblast-like state. Conversion can be induced by culture on collagen or exposure to acidic Fibroblast Growth Factor (aFGF). Furthermore, constitutive fibroblast-like transformation can be induced by transfection with cDNA encoding aFGF. Growth factor-producing clones exhibit increased invasive and metastatic properties as compared with non-FGF-producing control cells. This model may provide increased understanding of the role of the different adhesion molecules in processes involving cell remodeling, such as tumor spread and development of metastases.", "contents": "[Adhesion and mobility of embryonic and tumoral cells]. Regulation of a number of adhesion molecules during neural crest cell migration was studied. The neural crest, a transient embryonic neural epithelium structure, undergoes mesenchymal transformation (epithelial-mesenchymal transition). The cells then migrate, giving rise to a variety of elements including the peripheral nervous system and melanocytes. During migration, neural crest cells do not express functional cell Adhesion Molecules but interact specifically with cell-binding domains in fibronectin molecules. A rat bladder carcinoma cell line was used as an in vitro model to study conversion of epithelial cells to a migratory fibroblast-like state. Conversion can be induced by culture on collagen or exposure to acidic Fibroblast Growth Factor (aFGF). Furthermore, constitutive fibroblast-like transformation can be induced by transfection with cDNA encoding aFGF. Growth factor-producing clones exhibit increased invasive and metastatic properties as compared with non-FGF-producing control cells. This model may provide increased understanding of the role of the different adhesion molecules in processes involving cell remodeling, such as tumor spread and development of metastases."} {"id": "PMID:1283013", "title": "Exercise training: significance of regional alterations in serotonin metabolism of rat brain in relation to antidepressant effect of exercise.", "content": "Alterations of 5HT and its chief metabolite 5HIAA were studied in four regions of the rat brain following acute 1-h swim exercise and 4 week chronic swim exercise (30 min/day, 6 days per week). Acute exercise significantly increased the synthesis and metabolism of 5HT in brain stem. Hypothalamus also showed increased levels of 5HT. However, no changes were observed in the cerebral cortex and hippocampus. Chronic exercise activated not only the synthesis but also the metabolism of 5HT in the cerebral cortex; this neuronal adaptation was sustained even 1 week after the termination of training. In brain stem, increased 5HT turnover was observed immediately after training. In hypothalamus, decrease in 5HT and 5HIAA levels occurred immediately after training, followed by a rebound increase in their levels after 1 week posttraining rest. In hippocampus, a delayed effect was observed, because 5HT level was unaltered immediately after the training, but its turnover decreased after 1 week rest. These findings have been discussed in an attempt to explain the antidepressant effect of exercise based on the 5HT deficiency theory of endogenous depression.", "contents": "Exercise training: significance of regional alterations in serotonin metabolism of rat brain in relation to antidepressant effect of exercise. Alterations of 5HT and its chief metabolite 5HIAA were studied in four regions of the rat brain following acute 1-h swim exercise and 4 week chronic swim exercise (30 min/day, 6 days per week). Acute exercise significantly increased the synthesis and metabolism of 5HT in brain stem. Hypothalamus also showed increased levels of 5HT. However, no changes were observed in the cerebral cortex and hippocampus. Chronic exercise activated not only the synthesis but also the metabolism of 5HT in the cerebral cortex; this neuronal adaptation was sustained even 1 week after the termination of training. In brain stem, increased 5HT turnover was observed immediately after training. In hypothalamus, decrease in 5HT and 5HIAA levels occurred immediately after training, followed by a rebound increase in their levels after 1 week posttraining rest. In hippocampus, a delayed effect was observed, because 5HT level was unaltered immediately after the training, but its turnover decreased after 1 week rest. These findings have been discussed in an attempt to explain the antidepressant effect of exercise based on the 5HT deficiency theory of endogenous depression."} {"id": "PMID:1283014", "title": "Positron emission tomography with 18F-dopa: interpretation and biological correlates in nonhuman primates.", "content": "Positron emission tomography (PET) was carried out, with 18F-DOPA as a ligand, in normal control monkeys and \"parkinsonian\" monkeys who had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The following approaches were used in data analysis: ratio of 18F accumulation in specific to nonspecific brain areas and 18F-DOPA influx constant obtained using either the actual plasma 18F-DOPA or the 18F activity in a nonspecific brain area as the input function. The results from these analyses were compared to one another and to biological parameters relevant to dopaminergic function. The striatum/cortex ratio and the rate constant calculated from plasma 18F-DOPA appeared to be the most sensitive analytic techniques.", "contents": "Positron emission tomography with 18F-dopa: interpretation and biological correlates in nonhuman primates. Positron emission tomography (PET) was carried out, with 18F-DOPA as a ligand, in normal control monkeys and \"parkinsonian\" monkeys who had been treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. The following approaches were used in data analysis: ratio of 18F accumulation in specific to nonspecific brain areas and 18F-DOPA influx constant obtained using either the actual plasma 18F-DOPA or the 18F activity in a nonspecific brain area as the input function. The results from these analyses were compared to one another and to biological parameters relevant to dopaminergic function. The striatum/cortex ratio and the rate constant calculated from plasma 18F-DOPA appeared to be the most sensitive analytic techniques."} {"id": "PMID:1283020", "title": "Airway epithelial cells enhance eosinophil survival.", "content": "Guinea pig and human eosinophils were co-cultured with or without epithelial cells (controls). Eosinophil survival was enhanced in the presence of the cultured epithelial cells in a number-dependent fashion. Further, supernatants from cultured epithelial cells also enhanced eosinophil survival. Both a monoclonal antibody to GM-CSF and indomethacin inhibited these epithelial-cell-mediated effects, and GM-CSF and PGE2 were shown to prolong eosinophil survival. These findings indicate that airway epithelial cells can enhance eosinophil survival. It is suggested that the mechanism may involve GM-CSF and PGE2 generation.", "contents": "Airway epithelial cells enhance eosinophil survival. Guinea pig and human eosinophils were co-cultured with or without epithelial cells (controls). Eosinophil survival was enhanced in the presence of the cultured epithelial cells in a number-dependent fashion. Further, supernatants from cultured epithelial cells also enhanced eosinophil survival. Both a monoclonal antibody to GM-CSF and indomethacin inhibited these epithelial-cell-mediated effects, and GM-CSF and PGE2 were shown to prolong eosinophil survival. These findings indicate that airway epithelial cells can enhance eosinophil survival. It is suggested that the mechanism may involve GM-CSF and PGE2 generation."} {"id": "PMID:1283021", "title": "Scatter macular photocoagulation for subfoveal neovascular membranes in age-related macular degeneration. A pilot study.", "content": "Forty eyes with age-related macular degeneration and a choroidal neovascular membrane involving the entire foveal avascular zone were enrolled in a pilot study to evaluate an unconventional photocoagulation technique that was postulated to stimulate inhibitors of neovascularization. Eighteen (45%) eyes were treated with extrafoveal scatter macular photocoagulation, and 22 (55%) eyes were treated with this type of photocoagulation and focal extrafoveal ablation of the choroidal neovascular membrane. The eyes were followed for at least 1 year and up to 4 years (average, 2.4 years). One to 7 months after treatment, approximately 45% of the membranes treated with each technique did not leak fluorescein during angiography. The absence of leakage was associated with better visual acuity, but this difference was not statistically significant. At the beginning of the study, the visual acuity was 20/200 or better in 32 eyes (80%) and 20/80 or better in 11 (28%). At the conclusion of the study, the visual acuity was 20/200 or better in 21 eyes (53%) and 20/80 or better in 7 (18%). After treatment, 24 eyes (60%) had the same or better (plus or minus two lines) visual acuities. Compared with eyes in natural history studies, those treated with scatter macular photocoagulation had less visual loss from baseline but did not recover acuity of 20/100 or better more frequently. There was no difference in results between these two methods of treatment.", "contents": "Scatter macular photocoagulation for subfoveal neovascular membranes in age-related macular degeneration. A pilot study. Forty eyes with age-related macular degeneration and a choroidal neovascular membrane involving the entire foveal avascular zone were enrolled in a pilot study to evaluate an unconventional photocoagulation technique that was postulated to stimulate inhibitors of neovascularization. Eighteen (45%) eyes were treated with extrafoveal scatter macular photocoagulation, and 22 (55%) eyes were treated with this type of photocoagulation and focal extrafoveal ablation of the choroidal neovascular membrane. The eyes were followed for at least 1 year and up to 4 years (average, 2.4 years). One to 7 months after treatment, approximately 45% of the membranes treated with each technique did not leak fluorescein during angiography. The absence of leakage was associated with better visual acuity, but this difference was not statistically significant. At the beginning of the study, the visual acuity was 20/200 or better in 32 eyes (80%) and 20/80 or better in 11 (28%). At the conclusion of the study, the visual acuity was 20/200 or better in 21 eyes (53%) and 20/80 or better in 7 (18%). After treatment, 24 eyes (60%) had the same or better (plus or minus two lines) visual acuities. Compared with eyes in natural history studies, those treated with scatter macular photocoagulation had less visual loss from baseline but did not recover acuity of 20/100 or better more frequently. There was no difference in results between these two methods of treatment."} {"id": "PMID:1283022", "title": "Atypical parafoveal telangiectasis with subsequent anterior and posterior segment neovascularization.", "content": "Bilateral parafoveal telangiectasis typically includes the presence of fluorescein staining of outer retinal capillaries, no macular ischemia, right-angled venules, and migration of pigment along these venules. In the bilateral form, atypical parafoveal telangiectasis with macular ischemia but without right-angled venules or migration of pigment along these venules has been reported in only five patients previously. An atypical case is presented of bilateral parafoveal telangiectasis complicated, not only by areas of macular nonperfusion, but also by peripheral ischemia with subsequent anterior and posterior segment neovascularization in the absence of any systemic abnormalities. As in previously reported cases, this patient had no evidence of right-angled venules or pigment migration. Pan-retinal photocoagulation resolved the rubeosis and caused regression of the retinal neovascularization.", "contents": "Atypical parafoveal telangiectasis with subsequent anterior and posterior segment neovascularization. Bilateral parafoveal telangiectasis typically includes the presence of fluorescein staining of outer retinal capillaries, no macular ischemia, right-angled venules, and migration of pigment along these venules. In the bilateral form, atypical parafoveal telangiectasis with macular ischemia but without right-angled venules or migration of pigment along these venules has been reported in only five patients previously. An atypical case is presented of bilateral parafoveal telangiectasis complicated, not only by areas of macular nonperfusion, but also by peripheral ischemia with subsequent anterior and posterior segment neovascularization in the absence of any systemic abnormalities. As in previously reported cases, this patient had no evidence of right-angled venules or pigment migration. Pan-retinal photocoagulation resolved the rubeosis and caused regression of the retinal neovascularization."} {"id": "PMID:1283025", "title": "Transurethral incision of the prostate: a viable alternative to transurethral resection.", "content": "TUIP has been shown to be an effective method of relieving urinary outflow obstruction caused by BPH when prostatic size is 30 g or less. This is the situation for approximately 80% of patients undergoing TURP today. The long-term results of TUIP are quite favorable when compared with those of TURP. It is an easier technique to master than TURP. In addition, TUIP has a reduced operative time, little intraoperative and postoperative hemorrhage, reduced incidence of dilutional hyponatremia (TUR syndrome), and decreased length of hospitalization. TUIP also offers a lower risk of complications, especially with regard to impotence and retrograde ejaculation. This makes TUIP particularly well suited for patients in whom maintenance of sexual function is an important consideration. TUIP is also indicated in chronically ill, debilitated patients in whom the risk of anesthesia-related complications is high. Orandi and Graversen et al have shown that TUIP can be satisfactorily performed using only local anesthesia in high risk patients. However, TUIP is not without disadvantages. It is not effective for patients with a prominent median lobe or those with a markedly enlarged prostate gland (greater than 30 g). Another disadvantage is that no tissue is obtained for pathological analysis. Thus, all patients undergoing TUIP should be evaluated preoperatively with both a serum prostate-specific antigen determination and a meticulous digital rectal examination. As cost containment becomes a key factor for our health care system, it is quite likely that TUIP, as well as other less invasive procedures, will have expanded indications. Although the role of TURP in the management of very large prostates causing bladder outlet obstruction is not in question, smaller glands might be better managed with such a treatment as TUIP. As indicated earlier in this report, 80% of patients undergoing TURP could be effectively treated with TUIP--a less invasive, more cost effective treatment that has fewer associated side effects than TURP. Without question, TUIP is a grossly underutilized procedure in 1992. However, its future appears bright as more urologic surgeons are becoming aware of its many advantages and excellent long-term results.", "contents": "Transurethral incision of the prostate: a viable alternative to transurethral resection. TUIP has been shown to be an effective method of relieving urinary outflow obstruction caused by BPH when prostatic size is 30 g or less. This is the situation for approximately 80% of patients undergoing TURP today. The long-term results of TUIP are quite favorable when compared with those of TURP. It is an easier technique to master than TURP. In addition, TUIP has a reduced operative time, little intraoperative and postoperative hemorrhage, reduced incidence of dilutional hyponatremia (TUR syndrome), and decreased length of hospitalization. TUIP also offers a lower risk of complications, especially with regard to impotence and retrograde ejaculation. This makes TUIP particularly well suited for patients in whom maintenance of sexual function is an important consideration. TUIP is also indicated in chronically ill, debilitated patients in whom the risk of anesthesia-related complications is high. Orandi and Graversen et al have shown that TUIP can be satisfactorily performed using only local anesthesia in high risk patients. However, TUIP is not without disadvantages. It is not effective for patients with a prominent median lobe or those with a markedly enlarged prostate gland (greater than 30 g). Another disadvantage is that no tissue is obtained for pathological analysis. Thus, all patients undergoing TUIP should be evaluated preoperatively with both a serum prostate-specific antigen determination and a meticulous digital rectal examination. As cost containment becomes a key factor for our health care system, it is quite likely that TUIP, as well as other less invasive procedures, will have expanded indications. Although the role of TURP in the management of very large prostates causing bladder outlet obstruction is not in question, smaller glands might be better managed with such a treatment as TUIP. As indicated earlier in this report, 80% of patients undergoing TURP could be effectively treated with TUIP--a less invasive, more cost effective treatment that has fewer associated side effects than TURP. Without question, TUIP is a grossly underutilized procedure in 1992. However, its future appears bright as more urologic surgeons are becoming aware of its many advantages and excellent long-term results."} {"id": "PMID:1283028", "title": "[Suicide in the Ravensburg/Oberschwaben area. Results of a study of 508 suicides based on criminal police records].", "content": "On the basis of criminal police files we studied 508 suicides which happened between 1970 up to 1981 in the Ravensburg area in southern Germany. The police files also included medical records about in- or outpatient psychiatric treatment and also data about former violent behaviour. Mental disease as follows were most frequent: Depression 66% (diagnoses were made according to IDC-0 by two doctors under supervision of two senior psychiatrists; ICD-9: 300.4, 309.0 and 309.1 22%, ICD-9 296.1, 296.3 7.1% of the entire suicide group); neuroses and personality disorders 19%, addition, especially alcoholism, 28%. No psychiatric diagnosis could be made retrospectively in 10.6% (54 suicides). Sign in the presuicidal development like depressive symptoms, hopelessness and feelings of having no future, sleeping disturbances, feelings of guilt and anxiety, inner restlessness, but also changes in the direction of serenity and relaxation, treats of suicidal behaviour and reactions of the family and environment were reported showing a broad span of reactions from lack of perception to wrong interpretation. 15% of the suicides had also criminal activities in their former history. From a psychiatric point of view, improved diagnostic and therapeutic procedures in the treatment of the mentally ill, especially in the field of outpatient medical care of depressive and addictive patients, and better information of the relatives is to be demanded in order to prevent suicides.", "contents": "[Suicide in the Ravensburg/Oberschwaben area. Results of a study of 508 suicides based on criminal police records]. On the basis of criminal police files we studied 508 suicides which happened between 1970 up to 1981 in the Ravensburg area in southern Germany. The police files also included medical records about in- or outpatient psychiatric treatment and also data about former violent behaviour. Mental disease as follows were most frequent: Depression 66% (diagnoses were made according to IDC-0 by two doctors under supervision of two senior psychiatrists; ICD-9: 300.4, 309.0 and 309.1 22%, ICD-9 296.1, 296.3 7.1% of the entire suicide group); neuroses and personality disorders 19%, addition, especially alcoholism, 28%. No psychiatric diagnosis could be made retrospectively in 10.6% (54 suicides). Sign in the presuicidal development like depressive symptoms, hopelessness and feelings of having no future, sleeping disturbances, feelings of guilt and anxiety, inner restlessness, but also changes in the direction of serenity and relaxation, treats of suicidal behaviour and reactions of the family and environment were reported showing a broad span of reactions from lack of perception to wrong interpretation. 15% of the suicides had also criminal activities in their former history. From a psychiatric point of view, improved diagnostic and therapeutic procedures in the treatment of the mentally ill, especially in the field of outpatient medical care of depressive and addictive patients, and better information of the relatives is to be demanded in order to prevent suicides."} {"id": "PMID:1283029", "title": "[Results of percutaneous chemonucleolysis in lumbar disk hernia].", "content": "The percutaneous interventions have gained widespread acceptance for operative treatment of certain lumbar disc herniations. During recent years, percutaneous nucleotomy and laser discolysis replaced more and more the older technique of chemonucleolysis. Reports of anaphylactic shocks and severe neurological complications as well as unsatisfaction with the results of chemonucleolysis were responsible for this change. The basic mechanical concept of reduction of the intradiscal pressure remains the same with the newer methods. At the Inselspital percutaneous nucleotomy replaced chemonucleolysis in 1990. The results of chemonucleolysis were analysed with the aim of quantifying the efficiency of the percutaneous approach among our patient population. A total of 111 patients underwent chemonucleolysis between 1984 and 1989. The indication for the intervention was based on a several month history of lumbosciatica and a correlating radiological finding of disc protrusion or limited herniation. One case of anaphylaxis was the only serious perioperative complication. Upon follow-up examination approximately 2 months later, 54% of the patients were satisfied with the result, 27% reported an unchanged condition, and 19% had more pain than prior to the intervention. These results appear insufficient for an intervention associated with a non-negligible risk. Reduction of the nucleus pulposus appears often not to be an efficient mechanical concept for the treatment of disc protrusions and herniations.", "contents": "[Results of percutaneous chemonucleolysis in lumbar disk hernia]. The percutaneous interventions have gained widespread acceptance for operative treatment of certain lumbar disc herniations. During recent years, percutaneous nucleotomy and laser discolysis replaced more and more the older technique of chemonucleolysis. Reports of anaphylactic shocks and severe neurological complications as well as unsatisfaction with the results of chemonucleolysis were responsible for this change. The basic mechanical concept of reduction of the intradiscal pressure remains the same with the newer methods. At the Inselspital percutaneous nucleotomy replaced chemonucleolysis in 1990. The results of chemonucleolysis were analysed with the aim of quantifying the efficiency of the percutaneous approach among our patient population. A total of 111 patients underwent chemonucleolysis between 1984 and 1989. The indication for the intervention was based on a several month history of lumbosciatica and a correlating radiological finding of disc protrusion or limited herniation. One case of anaphylaxis was the only serious perioperative complication. Upon follow-up examination approximately 2 months later, 54% of the patients were satisfied with the result, 27% reported an unchanged condition, and 19% had more pain than prior to the intervention. These results appear insufficient for an intervention associated with a non-negligible risk. Reduction of the nucleus pulposus appears often not to be an efficient mechanical concept for the treatment of disc protrusions and herniations."} {"id": "PMID:1283030", "title": "[Psychosocial factors and follow-up of depressive disease].", "content": "In a one-year follow-up study 187 inpatients were studied using structured and semistructured interviews (Diagnostic Interview Schedule, M\u00fcnchner Ereignisliste, Social Interview Schedule). In order to predict the course of depression we focused on psychosocial factors and their influence on the course of depression. The severity of depression at discharge and negative life events during the follow-up period could be identified as the main influence factors. Results suggest reciprocal influence between illness and social conditions, especially illness and marital relations. Marital dysfunctioning at follow-up was reported significantly more often by patients with unfavourable outcome, whereas patients who recovered did not differ from the control group in their marital conditions. The results suppose the value of social variables in the prediction of the course of illness. A few implications on these findings for therapeutic process are discussed.", "contents": "[Psychosocial factors and follow-up of depressive disease]. In a one-year follow-up study 187 inpatients were studied using structured and semistructured interviews (Diagnostic Interview Schedule, M\u00fcnchner Ereignisliste, Social Interview Schedule). In order to predict the course of depression we focused on psychosocial factors and their influence on the course of depression. The severity of depression at discharge and negative life events during the follow-up period could be identified as the main influence factors. Results suggest reciprocal influence between illness and social conditions, especially illness and marital relations. Marital dysfunctioning at follow-up was reported significantly more often by patients with unfavourable outcome, whereas patients who recovered did not differ from the control group in their marital conditions. The results suppose the value of social variables in the prediction of the course of illness. A few implications on these findings for therapeutic process are discussed."} {"id": "PMID:1283031", "title": "[Are sex differences in schizophrenia stable on a transnational basis?].", "content": "The ABC-Schizophrenia-Study (H\u00e4fner et al. 1991), investigating a large, representative sample of 267 first admissions, did not find any gender differences in the lifetime morbidity risk for this disorder or in the frequency of nuclear symptoms in male and female schizophrenic patients. Marked gender differences, however, could be detected regarding the age at onset and its distribution and regarding illness behavior and certain secondary symptoms. The transnational stability of these findings was tested with data from the WHO studies \"On Assessment and Reduction of Psychiatric Disability\" (including 510 patients from 7 centres) and on \"Determinants of Outcome of Severe Mental Disorders\" (with 1,292 patients from 11 centres). Studying pooled data sets from the studies minimized centre-specific selection effects on sampling. Major results of the ABC-Schizophrenia-Study were validated: the lack of a gender difference in the morbidity risk (cumulative lifetime incidence rates) for schizophrenia; lower mean age at first admission in males; an early, marked peak in the distribution of the age at onset in males; a later and broader peak in this distribution in females with a second peak after age 40-45; equal frequency of nuclear symptoms in both sexes; gender differences in some specific contents of delusions, secondary affective symptoms, social adjustment and illness behavior.", "contents": "[Are sex differences in schizophrenia stable on a transnational basis?]. The ABC-Schizophrenia-Study (H\u00e4fner et al. 1991), investigating a large, representative sample of 267 first admissions, did not find any gender differences in the lifetime morbidity risk for this disorder or in the frequency of nuclear symptoms in male and female schizophrenic patients. Marked gender differences, however, could be detected regarding the age at onset and its distribution and regarding illness behavior and certain secondary symptoms. The transnational stability of these findings was tested with data from the WHO studies \"On Assessment and Reduction of Psychiatric Disability\" (including 510 patients from 7 centres) and on \"Determinants of Outcome of Severe Mental Disorders\" (with 1,292 patients from 11 centres). Studying pooled data sets from the studies minimized centre-specific selection effects on sampling. Major results of the ABC-Schizophrenia-Study were validated: the lack of a gender difference in the morbidity risk (cumulative lifetime incidence rates) for schizophrenia; lower mean age at first admission in males; an early, marked peak in the distribution of the age at onset in males; a later and broader peak in this distribution in females with a second peak after age 40-45; equal frequency of nuclear symptoms in both sexes; gender differences in some specific contents of delusions, secondary affective symptoms, social adjustment and illness behavior."} {"id": "PMID:1283032", "title": "[Personality of schizophrenic and schizoaffective patients].", "content": "At time of discharge 33 patients with ICD-9 schizophrenia and 16 patients with ICD-9 schizoaffective psychosis were assessed by the Freiburg Personality Inventory (FPI). Psychological profiles were analyzed individually and compared to controls. In addition, a hierarchical cluster analysis was carried out. Psychopathological findings at time of discharge were documented by the AMDP system. Impact of psychopathology on response behavior in the FPI was not evident. There were but few schizophrenic or schizoaffective patients without any abnormal FPI score. For the schizophrenics abnormal (high and low) scores could especially be found on the scales \"Nervousness\", \"Depressiveness\" and \"Masculinity\", for the schizoaffective patients on the scales \"Nervousness\", \"Depressiveness\", \"Excitability\", \"Extraversion\" and \"Neuroticism\". With regard to personality both groups turned out to be heterogenous. The schizophrenics differed significantly from the controls by higher means on the scales \"Nervousness\" and \"Depressiveness\" and a lower mean on the scale \"Masculinity\". The schizoaffective patients differed significantly from the controls by higher means on the scales \"Depressiveness\" and \"Inhibition\". Hierarchical cluster analysis resulted in 3 clusters for the schizophrenics: 1. introverted-schizoid type (42%), 2. extraverted-aggressive type (36%), 3. normal type (22%), and 2 clusters for the schizoaffective patients: 1. emotional labile type (56%), 2 normal type (44%). Results are compared to literature.", "contents": "[Personality of schizophrenic and schizoaffective patients]. At time of discharge 33 patients with ICD-9 schizophrenia and 16 patients with ICD-9 schizoaffective psychosis were assessed by the Freiburg Personality Inventory (FPI). Psychological profiles were analyzed individually and compared to controls. In addition, a hierarchical cluster analysis was carried out. Psychopathological findings at time of discharge were documented by the AMDP system. Impact of psychopathology on response behavior in the FPI was not evident. There were but few schizophrenic or schizoaffective patients without any abnormal FPI score. For the schizophrenics abnormal (high and low) scores could especially be found on the scales \"Nervousness\", \"Depressiveness\" and \"Masculinity\", for the schizoaffective patients on the scales \"Nervousness\", \"Depressiveness\", \"Excitability\", \"Extraversion\" and \"Neuroticism\". With regard to personality both groups turned out to be heterogenous. The schizophrenics differed significantly from the controls by higher means on the scales \"Nervousness\" and \"Depressiveness\" and a lower mean on the scale \"Masculinity\". The schizoaffective patients differed significantly from the controls by higher means on the scales \"Depressiveness\" and \"Inhibition\". Hierarchical cluster analysis resulted in 3 clusters for the schizophrenics: 1. introverted-schizoid type (42%), 2. extraverted-aggressive type (36%), 3. normal type (22%), and 2 clusters for the schizoaffective patients: 1. emotional labile type (56%), 2 normal type (44%). Results are compared to literature."} {"id": "PMID:1283033", "title": "Myopathy associated with monoclonal gammopathy and leukoencephalopathy.", "content": "We report here two patients presenting a myopathy associated with a monoclonal gammopathy (of IgG lambda or IgA kappa type) and, in one case, also with a leukoencephalopathy. Possible etiopathological mechanisms between these neurological diseases and an immune disregulation are discussed.", "contents": "Myopathy associated with monoclonal gammopathy and leukoencephalopathy. We report here two patients presenting a myopathy associated with a monoclonal gammopathy (of IgG lambda or IgA kappa type) and, in one case, also with a leukoencephalopathy. Possible etiopathological mechanisms between these neurological diseases and an immune disregulation are discussed."} {"id": "PMID:1283035", "title": "A study of quality of life in cancer patients receiving palliative chemotherapy.", "content": "Although primary treatment for cancer has been associated with psychosocial distress, less research has focused on patients with advanced disease. Traditionally, the outcomes of treatment have been assessed using biomedical criteria, including tumour regression, progression and survival. It is argued that these data are inadequate to understand the impact of cancer upon the patient. Instead, quality of life considerations are crucial when treatments are aversive, especially when the aims are palliative rather than curative. Fifty-three patients with advanced breast cancer or ovarian cancer were studied prospectively for 6 months to assess whether the site and method of chemotherapy administration influenced their quality of life. Patients received palliative chemotherapy either at home or in hospital. Quality of life was operationalized as measurement of anxiety, depression, self-esteem, health locus of control, physical performance and symptoms. In addition, semi-structured interviews explored social roles, relationships, and perceptions of treatment. Hospital administered chemotherapy was perceived to be most distressing. Regression analysis indicated that anxiety and depression accounted for most of the variance in quality of life. Patients who died during the study 13 (24%) experienced considerable psychological and physical morbidity. Women over 60 years, experienced less psychological and physical distress. Quality of life broadens the criteria by which cancer treatments are evaluated, to include the experience of the patient.", "contents": "A study of quality of life in cancer patients receiving palliative chemotherapy. Although primary treatment for cancer has been associated with psychosocial distress, less research has focused on patients with advanced disease. Traditionally, the outcomes of treatment have been assessed using biomedical criteria, including tumour regression, progression and survival. It is argued that these data are inadequate to understand the impact of cancer upon the patient. Instead, quality of life considerations are crucial when treatments are aversive, especially when the aims are palliative rather than curative. Fifty-three patients with advanced breast cancer or ovarian cancer were studied prospectively for 6 months to assess whether the site and method of chemotherapy administration influenced their quality of life. Patients received palliative chemotherapy either at home or in hospital. Quality of life was operationalized as measurement of anxiety, depression, self-esteem, health locus of control, physical performance and symptoms. In addition, semi-structured interviews explored social roles, relationships, and perceptions of treatment. Hospital administered chemotherapy was perceived to be most distressing. Regression analysis indicated that anxiety and depression accounted for most of the variance in quality of life. Patients who died during the study 13 (24%) experienced considerable psychological and physical morbidity. Women over 60 years, experienced less psychological and physical distress. Quality of life broadens the criteria by which cancer treatments are evaluated, to include the experience of the patient."} {"id": "PMID:1283038", "title": "[Use and abuse of visual aids--presentation technique].", "content": "In today's health service, doctors cannot avoid teaching or lectures. Visual aids are an important part of any successful presentation. Adequate overheads and slides can be easily made using ordinary office equipment and simple cameras. Modern computers and laser printers are also an exciting medium for producing visual aids. Nevertheless, if the talk is to achieve its purpose, good pictures must be presented in the correct way, along with an absorbing commentary. Both these aspects of presentation technique require careful preparation, but are seldom taught to medical students or junior staff as a necessary tool for their future work as doctors.", "contents": "[Use and abuse of visual aids--presentation technique]. In today's health service, doctors cannot avoid teaching or lectures. Visual aids are an important part of any successful presentation. Adequate overheads and slides can be easily made using ordinary office equipment and simple cameras. Modern computers and laser printers are also an exciting medium for producing visual aids. Nevertheless, if the talk is to achieve its purpose, good pictures must be presented in the correct way, along with an absorbing commentary. Both these aspects of presentation technique require careful preparation, but are seldom taught to medical students or junior staff as a necessary tool for their future work as doctors."} {"id": "PMID:1283039", "title": "Neovascularization effect with He-Ne laser in the rat trachea.", "content": "The tracheal tissue of a rat was heterotopically transplanted beneath the abdominal skin of a syngenetic rat, and the transplanted graft was irradiated with a He-Ne laser (2.41 J/cm2). Four or seven days following transplantation, Chinese ink staining was used to ascertain the number of newly generated vessels. Rats sacrificed on day 4 were divided into 3 groups, according to the number of laser irradiation treatments: A0, A2, and A4. Similarly, rats sacrificed on day 7 were divided into groups B0, B2, and B4. Among the A groups, vascular counts were 49.5 +/- 31.1 in group A0 (n = 6), 108.9 +/- 34.7 in group A2 (n = 7), and 90.9 +/- 24.6 in group A4 (n = 4). Neovascularization was significantly more pronounced in the irradiated groups that in the non-irradiated group. In the B groups, vascular counts were 148 +/- 58 in group B0 (n = 6), 146 +/- 56 in group B2 (n = 5), and 147 +/- 49 in group B4 (n = 5). There was no significant difference between the irradiated and non-irradiated B groups. Laser irradiation was determined to stimulate neovascularization, and the possibility of a clinical application for this procedure was suggested.", "contents": "Neovascularization effect with He-Ne laser in the rat trachea. The tracheal tissue of a rat was heterotopically transplanted beneath the abdominal skin of a syngenetic rat, and the transplanted graft was irradiated with a He-Ne laser (2.41 J/cm2). Four or seven days following transplantation, Chinese ink staining was used to ascertain the number of newly generated vessels. Rats sacrificed on day 4 were divided into 3 groups, according to the number of laser irradiation treatments: A0, A2, and A4. Similarly, rats sacrificed on day 7 were divided into groups B0, B2, and B4. Among the A groups, vascular counts were 49.5 +/- 31.1 in group A0 (n = 6), 108.9 +/- 34.7 in group A2 (n = 7), and 90.9 +/- 24.6 in group A4 (n = 4). Neovascularization was significantly more pronounced in the irradiated groups that in the non-irradiated group. In the B groups, vascular counts were 148 +/- 58 in group B0 (n = 6), 146 +/- 56 in group B2 (n = 5), and 147 +/- 49 in group B4 (n = 5). There was no significant difference between the irradiated and non-irradiated B groups. Laser irradiation was determined to stimulate neovascularization, and the possibility of a clinical application for this procedure was suggested."} {"id": "PMID:1283041", "title": "Comparison of staining and concentration techniques for detection of Cryptosporidium oocysts in cat faecal specimens.", "content": "Modified Ziehl-Neelsen (MZN), auramine-phenol (A-P) and fluorescein isothiocyanate-labelled (FITC-labelled) monoclonal antibody (MAb) techniques were compared for detection of Cryptosporidium parvum oocysts in cat faecal specimens inoculated with known numbers of C. parvum oocysts. Of the three techniques, the FITC-labelled MAb technique detected more oocysts than the MZN and A-P techniques (P < 0.05), but A-P was more efficient than MZN (P < 0.05). Comparison of sucrose flotation, zinc sulphate (ZnSO4) flotation and formol-ether (F-E) sedimentation techniques revealed that F-E was the most efficient of the three (P < 0.05) for concentration of C. parvum oocysts from cat faecal specimens. On average, the F-E technique recovered 37% of oocysts from the original sample, whereas the sucrose and ZnSO4 flotation techniques recovered 33% and 11%, respectively. The findings of this study suggest that MZN and A-P staining are both useful for screening C. parvum oocysts in cat faecal materials containing 10(6) oocysts or more, but FITC-labelled MAb should be used when the number of oocysts is low. Also, the F-E sedimentation technique is recommended for concentrating oocysts in cat faecal specimens.", "contents": "Comparison of staining and concentration techniques for detection of Cryptosporidium oocysts in cat faecal specimens. Modified Ziehl-Neelsen (MZN), auramine-phenol (A-P) and fluorescein isothiocyanate-labelled (FITC-labelled) monoclonal antibody (MAb) techniques were compared for detection of Cryptosporidium parvum oocysts in cat faecal specimens inoculated with known numbers of C. parvum oocysts. Of the three techniques, the FITC-labelled MAb technique detected more oocysts than the MZN and A-P techniques (P < 0.05), but A-P was more efficient than MZN (P < 0.05). Comparison of sucrose flotation, zinc sulphate (ZnSO4) flotation and formol-ether (F-E) sedimentation techniques revealed that F-E was the most efficient of the three (P < 0.05) for concentration of C. parvum oocysts from cat faecal specimens. On average, the F-E technique recovered 37% of oocysts from the original sample, whereas the sucrose and ZnSO4 flotation techniques recovered 33% and 11%, respectively. The findings of this study suggest that MZN and A-P staining are both useful for screening C. parvum oocysts in cat faecal materials containing 10(6) oocysts or more, but FITC-labelled MAb should be used when the number of oocysts is low. Also, the F-E sedimentation technique is recommended for concentrating oocysts in cat faecal specimens."} {"id": "PMID:1283042", "title": "D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States.", "content": "If a genetic association between the D2 dopamine receptor genotype and alcoholism is mediated by altered dopamine function, then a stronger association might be found in alcoholics who are deviant in indices of dopamine function and by comparing alcoholics to nonalcoholics matched for ethnic origin. Therefore, we evaluated the D2/TaqI polymorphism in 29 impulsive violent alcoholic Finns, 17 nonimpulsive violent alcoholic Finns and 36 Finnish controls free of mental disorders, alcoholism and substance abuse. In 37 of the alcoholics, we measured cerebrospinal fluid (CSF) homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol. There was no relationship between D2/Taq 1 genotype and concentrations of these monoamine metabolites in this group, which exhibits lower CSF HVA and 5-HIAA as compared to controls. There was also no genotypic difference between Finnish alcoholics and nonalcoholic controls. The lack of relationship between D2/Taq1 genotype and HVA concentration was replicated in 24 Caucasian alcoholics in the United States.", "contents": "D2 dopamine receptor genotype and cerebrospinal fluid homovanillic acid, 5-hydroxyindoleacetic acid and 3-methoxy-4-hydroxyphenylglycol in alcoholics in Finland and the United States. If a genetic association between the D2 dopamine receptor genotype and alcoholism is mediated by altered dopamine function, then a stronger association might be found in alcoholics who are deviant in indices of dopamine function and by comparing alcoholics to nonalcoholics matched for ethnic origin. Therefore, we evaluated the D2/TaqI polymorphism in 29 impulsive violent alcoholic Finns, 17 nonimpulsive violent alcoholic Finns and 36 Finnish controls free of mental disorders, alcoholism and substance abuse. In 37 of the alcoholics, we measured cerebrospinal fluid (CSF) homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylglycol. There was no relationship between D2/Taq 1 genotype and concentrations of these monoamine metabolites in this group, which exhibits lower CSF HVA and 5-HIAA as compared to controls. There was also no genotypic difference between Finnish alcoholics and nonalcoholic controls. The lack of relationship between D2/Taq1 genotype and HVA concentration was replicated in 24 Caucasian alcoholics in the United States."} {"id": "PMID:1283043", "title": "Voltage, calcium, and stretch activated ionic channels and intracellular calcium in bone cells.", "content": "Embryonic chick bone cells express various types of ionic channels in their plasma membranes for as yet unresolved functions. Chick osteoclasts (OCL) have the richest spectrum of channel types. Specific for OCL is a K+ channel, which activates (opens) when the inside negative membrane potential (Vm) becomes more negative (hyperpolarization). This is consistent with findings of others on rat OCL. The membrane conductance constituted by these channels is called the inward rectifying K+ conductance (GKi), or inward rectifier, because the hyperpolarization-activated channels cause cell-inward K+ current to pass more easily through the membrane than outward K+ current. Besides GKi channels, OCL may express two other types of voltage-activated K+ channels. One constitutes the transient outward rectifying K+ conductance (GKto), which is activated upon making the membrane potential less negative (depolarization) but has a transient nature. This conductance favors transient K+ conduction in the cell-outward direction. The GKto also occurs in a small percentage of cells in osteoblast (OBL) and periosteal fibroblast (PFB) cultures. The other OCL K+ conductance, the GKCa, is activated by both membrane depolarization and a rise in [Ca2+]i. GKCa channels are also present in the other chick bone cell types, that is, OBL, osteocytes (OCY), and PFB. Furthermore, in excised patches of all bone cell types, channels have been found that conduct anions, including Cl- and phosphate ions. These channels are only active around Vm = 0 mV. While searching for a membrane mechanism for adaptation of bone to mechanical loading, we found stretch-activated channels in chick osteoclasts; other investigators have found stretch-activated cation channels (K+ or aselective) in rat and human osteogenic cell lines. In contrast to other studies on cell lines or OBL from other species, we have not found any of the classic macroscopic voltage-activated calcium conductances (GCa) in any of the chick bone cells under our experimental conditions. However, our fluorescence measurements of [Ca2+]i in single cells indicate the presence of Ca2+ conductive pathways through the plasma membrane of osteoblastic cells and osteoclasts, consistent with other studies. We discuss possible roles for GKi, GKCa, and anion channels in acid secretion by OCL and for stretch-activated channels in OCL locomotion.", "contents": "Voltage, calcium, and stretch activated ionic channels and intracellular calcium in bone cells. Embryonic chick bone cells express various types of ionic channels in their plasma membranes for as yet unresolved functions. Chick osteoclasts (OCL) have the richest spectrum of channel types. Specific for OCL is a K+ channel, which activates (opens) when the inside negative membrane potential (Vm) becomes more negative (hyperpolarization). This is consistent with findings of others on rat OCL. The membrane conductance constituted by these channels is called the inward rectifying K+ conductance (GKi), or inward rectifier, because the hyperpolarization-activated channels cause cell-inward K+ current to pass more easily through the membrane than outward K+ current. Besides GKi channels, OCL may express two other types of voltage-activated K+ channels. One constitutes the transient outward rectifying K+ conductance (GKto), which is activated upon making the membrane potential less negative (depolarization) but has a transient nature. This conductance favors transient K+ conduction in the cell-outward direction. The GKto also occurs in a small percentage of cells in osteoblast (OBL) and periosteal fibroblast (PFB) cultures. The other OCL K+ conductance, the GKCa, is activated by both membrane depolarization and a rise in [Ca2+]i. GKCa channels are also present in the other chick bone cell types, that is, OBL, osteocytes (OCY), and PFB. Furthermore, in excised patches of all bone cell types, channels have been found that conduct anions, including Cl- and phosphate ions. These channels are only active around Vm = 0 mV. While searching for a membrane mechanism for adaptation of bone to mechanical loading, we found stretch-activated channels in chick osteoclasts; other investigators have found stretch-activated cation channels (K+ or aselective) in rat and human osteogenic cell lines. In contrast to other studies on cell lines or OBL from other species, we have not found any of the classic macroscopic voltage-activated calcium conductances (GCa) in any of the chick bone cells under our experimental conditions. However, our fluorescence measurements of [Ca2+]i in single cells indicate the presence of Ca2+ conductive pathways through the plasma membrane of osteoblastic cells and osteoclasts, consistent with other studies. We discuss possible roles for GKi, GKCa, and anion channels in acid secretion by OCL and for stretch-activated channels in OCL locomotion."} {"id": "PMID:1283044", "title": "A novel microcarrier bead model to investigate bone cell responses to mechanical compression in vitro.", "content": "Periosteal cells grown in macroporous microcarrier bead columns were cyclically loaded with compressive force using a newly developed model. In response to 1/2 h of cyclic compression, RNA synthesis increased significantly by twofold, from 113.4 +/- 19.6 to 260.7 +/- 363 (p < 0.01) after 16 h, whereas DNA synthesis did not increase significantly after 24 h. The microcarrier bead model was calibrated using a linear volume displacement transducer with a range of strain magnitudes applied across the column of 1000-6000 microstrain.", "contents": "A novel microcarrier bead model to investigate bone cell responses to mechanical compression in vitro. Periosteal cells grown in macroporous microcarrier bead columns were cyclically loaded with compressive force using a newly developed model. In response to 1/2 h of cyclic compression, RNA synthesis increased significantly by twofold, from 113.4 +/- 19.6 to 260.7 +/- 363 (p < 0.01) after 16 h, whereas DNA synthesis did not increase significantly after 24 h. The microcarrier bead model was calibrated using a linear volume displacement transducer with a range of strain magnitudes applied across the column of 1000-6000 microstrain."} {"id": "PMID:1283046", "title": "Regulatory cells and cytokines involved in primary B lymphocyte production.", "content": "Based upon the above data, it is now possible to formulate a working model that defines the stages of B cell development on which stromal cells and their products act. During the initial stages of this process, pro-B cells which do not express Ig heavy or light chain protein or other non-Ig B lineage associated molecules develop into B220 and c mu expressing pre-B cells in response to a low (< 10 kD) molecular weight stromal cell derived factor. No defined interleukin or colony stimulating factor, including molecules such as KL and IL-7, can replace stromal cell conditioned medium in mediating this developmental step. There appears to be little cell proliferation associated with the differentiation of pro-B cells into pre-B cells. However, our data indicate that as precursors develop into B220 expressing B cell progenitors, they become sensitive to the proliferation stimulating effects of IL-7 and KL. These results are in accord with findings that progenitor cells that have undergone DJH rearrangements are particularly sensitive to KL and IL-7(18,19). The analysis of pre-B cells present in individual lymphoid colonies indicates that once cells have rearranged and expressed their Ig heavy chain genes, they are no longer sensitive to KL and IL-7. These observations are based on the fact that receptors for these cytokines are not expressed in stromal cell dependent pre-B cells and are consistent with kinetic studies showing that the maturation of pre-B cells into surface Ig expressing B lymphocytes is not dependent upon cell proliferation21.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Regulatory cells and cytokines involved in primary B lymphocyte production. Based upon the above data, it is now possible to formulate a working model that defines the stages of B cell development on which stromal cells and their products act. During the initial stages of this process, pro-B cells which do not express Ig heavy or light chain protein or other non-Ig B lineage associated molecules develop into B220 and c mu expressing pre-B cells in response to a low (< 10 kD) molecular weight stromal cell derived factor. No defined interleukin or colony stimulating factor, including molecules such as KL and IL-7, can replace stromal cell conditioned medium in mediating this developmental step. There appears to be little cell proliferation associated with the differentiation of pro-B cells into pre-B cells. However, our data indicate that as precursors develop into B220 expressing B cell progenitors, they become sensitive to the proliferation stimulating effects of IL-7 and KL. These results are in accord with findings that progenitor cells that have undergone DJH rearrangements are particularly sensitive to KL and IL-7(18,19). The analysis of pre-B cells present in individual lymphoid colonies indicates that once cells have rearranged and expressed their Ig heavy chain genes, they are no longer sensitive to KL and IL-7. These observations are based on the fact that receptors for these cytokines are not expressed in stromal cell dependent pre-B cells and are consistent with kinetic studies showing that the maturation of pre-B cells into surface Ig expressing B lymphocytes is not dependent upon cell proliferation21.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283051", "title": "[The onset mechanism of experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein].", "content": "In order to analyze the onset mechanism of experimental autoimmune uveoretinitis (EAU), two experimental models were used; one was EAU induced by one injection of purified bovine interphotoreceptor retinoid-binding protein (IRBP) with complete Freund's adjuvant in Lewis rat, and the other was an IRBP-induced autoimmune uveoretinitis that occurred spontaneously in nude (nu/nu) mice at 4 weeks of age reconstituted by the grafting of rat embryonic thymus (TG nude mouse). EAU develops when the IRBP-reactive lymphocytes in the regional lymph-nodes are activated. Activation begins when the T lymphocyte recognizes the peptide for the epitope bound to a major histocompatibility complex (MHC) molecule in the antigen-presenting cell by way of the T-cell receptor (TCR). In EAU, ten peptide residues p1182-1191 of the IRBP amino acid sequence, were revealed to be sufficiently capable of lymphocyte activation for EAU, and it was also shown that amino acid positions 1182W (tryptophane), 1185G (glycine), 1186V (valine) and 1188P (proline) of IRBP play important roles as the epitopes or agretopes in developing EAU. On the other hand, two amino acids of IRBP, amino acid positions 1182W (tryptophane) and 1194P (proline) were shown to be the agretopes inducing autoimmune uveoretinitis in the TG nude mouse. A study of the variable region of the TCR with a residual p1182-1194 specific T-cell line from the TG nude mouse revealed that as many as 96% utilized the T-cell receptor V beta 6 gene and that the peptide-MHC molecule complex was recognized by restricted receptors. Adhesion molecules such as ICAM-1 and LFA-1 were also found to play an important role as cofactors in activation of lymphocytes in the antigen-recognition process of EAU. Uveoretinitis seemed to result from an immune reaction in the eye occurring when the T lymphocyte arrives there, activating the immunological process. ICAM-1 and LFA-1 were also found to be involved in the infiltration process of inflammatory cells: our immunohistological examination revealed that ICAM-1 was present in the retinal pigment epithelium and epithelium of the ciliary body composing the blood-ocular barrier. In contrast, LFA-1 was expressed in the infiltrating cells. Finally, the tolerance of IRBP was discussed and it was experimentally demonstrated that the absence of IRBP-induced uveoretinitis in human beings and certain experimental animals resulted from endogenous IRBP serving as a tolerogen; we assumed that the breakdown of this self-tolerance would induce EAU due to thymic dysfunction or IRBP antigen injection.", "contents": "[The onset mechanism of experimental autoimmune uveoretinitis induced by interphotoreceptor retinoid-binding protein]. In order to analyze the onset mechanism of experimental autoimmune uveoretinitis (EAU), two experimental models were used; one was EAU induced by one injection of purified bovine interphotoreceptor retinoid-binding protein (IRBP) with complete Freund's adjuvant in Lewis rat, and the other was an IRBP-induced autoimmune uveoretinitis that occurred spontaneously in nude (nu/nu) mice at 4 weeks of age reconstituted by the grafting of rat embryonic thymus (TG nude mouse). EAU develops when the IRBP-reactive lymphocytes in the regional lymph-nodes are activated. Activation begins when the T lymphocyte recognizes the peptide for the epitope bound to a major histocompatibility complex (MHC) molecule in the antigen-presenting cell by way of the T-cell receptor (TCR). In EAU, ten peptide residues p1182-1191 of the IRBP amino acid sequence, were revealed to be sufficiently capable of lymphocyte activation for EAU, and it was also shown that amino acid positions 1182W (tryptophane), 1185G (glycine), 1186V (valine) and 1188P (proline) of IRBP play important roles as the epitopes or agretopes in developing EAU. On the other hand, two amino acids of IRBP, amino acid positions 1182W (tryptophane) and 1194P (proline) were shown to be the agretopes inducing autoimmune uveoretinitis in the TG nude mouse. A study of the variable region of the TCR with a residual p1182-1194 specific T-cell line from the TG nude mouse revealed that as many as 96% utilized the T-cell receptor V beta 6 gene and that the peptide-MHC molecule complex was recognized by restricted receptors. Adhesion molecules such as ICAM-1 and LFA-1 were also found to play an important role as cofactors in activation of lymphocytes in the antigen-recognition process of EAU. Uveoretinitis seemed to result from an immune reaction in the eye occurring when the T lymphocyte arrives there, activating the immunological process. ICAM-1 and LFA-1 were also found to be involved in the infiltration process of inflammatory cells: our immunohistological examination revealed that ICAM-1 was present in the retinal pigment epithelium and epithelium of the ciliary body composing the blood-ocular barrier. In contrast, LFA-1 was expressed in the infiltrating cells. Finally, the tolerance of IRBP was discussed and it was experimentally demonstrated that the absence of IRBP-induced uveoretinitis in human beings and certain experimental animals resulted from endogenous IRBP serving as a tolerogen; we assumed that the breakdown of this self-tolerance would induce EAU due to thymic dysfunction or IRBP antigen injection."} {"id": "PMID:1283052", "title": "[Immunotherapy in ocular diseases].", "content": "Basic and clinical studies on immunotherapy in immune-mediated ocular disorders, i.e. uveitis, allograft rejection in corneal transplantation and allergic conjunctivitis, were carried out using a variety of immunosuppressants, including immunophilin ligands (FK506 and cyclosporine). 1. In an animal model for uveitis, experimental autoimmune uveitis (EAU), immunophilin ligands were demonstrated in the rat and monkey to have unique immunological activities: (1) intense and prolonged suppression of EAU development, (2) therapeutic effects by treating animals only after disease onset, (3) selective suppression on cellular immune response to S-antigen, (4) induction of immunological tolerance and activation of antigen specific suppressor cells. Combination therapy with low doses of immunophilin ligand and other immunosuppressant was tested to achieve better effects with less side effects. A low dose of cyclosporine (2 mg/kg/day) with bucillamine (20 mg/kg/day) which suppresses antigen-presenting activity by macrophages caused much stronger suppression of EAU than the therapy with either cyclosporine or bucillamine alone. Similarly, a low dose of FK506 (0.1 mg/kg/day) with dexamethasone (0.01 mg/kg/day) caused stronger suppression of EAU. A multi-center clinical open trial of FK506 in refractory uveitis was carried out in Japan. A total of 40 cases of active uveitis in the posterior segment of the eye were treated with FK506 (0.05, 0.1 or 0.2 mg/kg/day) and the mean observation period was 26.2 +/- 12.4 weeks. FK506 therapy improved uveitis in 60% of all cases including 47% of patients resistant to previous therapy with cyclosporine. FK506 significantly suppressed the number of uveitis attacks in patients with Beh\u00e7et's disease. As for the side effects, 22.5% of patients showed abnormal values of renal function on FK506. The trough level of FK506 in whole blood correlated with adverse side effects as well as with therapeutic effect on uveitis, and it should be maintained between 15 and 25 ng/ml. 2. Effects of immunophilin ligands on the allograft rejection in corneal transplantation was examined in the rat. Fisher rat were used as donors and Lewis rats as recipients. This combination caused 100% rejection by 2-3 weeks after surgery as indicated by (1) edema, opacity and neovascularization in the graft, (2) infiltration of a variety of immune cells demonstrated by immunohistological examination and (3) high mixed leukocyte reaction (MLR). Systemic administration of cyclosporine (10 mg/kg/day) or FK506 (0.3, 1, 3 mg/kg/day) suppressed the allograft rejection. In addition, topical instillation of FK506 (0.3%) was effective to prolong the graft survival as long as the topical therapy continued.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "[Immunotherapy in ocular diseases]. Basic and clinical studies on immunotherapy in immune-mediated ocular disorders, i.e. uveitis, allograft rejection in corneal transplantation and allergic conjunctivitis, were carried out using a variety of immunosuppressants, including immunophilin ligands (FK506 and cyclosporine). 1. In an animal model for uveitis, experimental autoimmune uveitis (EAU), immunophilin ligands were demonstrated in the rat and monkey to have unique immunological activities: (1) intense and prolonged suppression of EAU development, (2) therapeutic effects by treating animals only after disease onset, (3) selective suppression on cellular immune response to S-antigen, (4) induction of immunological tolerance and activation of antigen specific suppressor cells. Combination therapy with low doses of immunophilin ligand and other immunosuppressant was tested to achieve better effects with less side effects. A low dose of cyclosporine (2 mg/kg/day) with bucillamine (20 mg/kg/day) which suppresses antigen-presenting activity by macrophages caused much stronger suppression of EAU than the therapy with either cyclosporine or bucillamine alone. Similarly, a low dose of FK506 (0.1 mg/kg/day) with dexamethasone (0.01 mg/kg/day) caused stronger suppression of EAU. A multi-center clinical open trial of FK506 in refractory uveitis was carried out in Japan. A total of 40 cases of active uveitis in the posterior segment of the eye were treated with FK506 (0.05, 0.1 or 0.2 mg/kg/day) and the mean observation period was 26.2 +/- 12.4 weeks. FK506 therapy improved uveitis in 60% of all cases including 47% of patients resistant to previous therapy with cyclosporine. FK506 significantly suppressed the number of uveitis attacks in patients with Beh\u00e7et's disease. As for the side effects, 22.5% of patients showed abnormal values of renal function on FK506. The trough level of FK506 in whole blood correlated with adverse side effects as well as with therapeutic effect on uveitis, and it should be maintained between 15 and 25 ng/ml. 2. Effects of immunophilin ligands on the allograft rejection in corneal transplantation was examined in the rat. Fisher rat were used as donors and Lewis rats as recipients. This combination caused 100% rejection by 2-3 weeks after surgery as indicated by (1) edema, opacity and neovascularization in the graft, (2) infiltration of a variety of immune cells demonstrated by immunohistological examination and (3) high mixed leukocyte reaction (MLR). Systemic administration of cyclosporine (10 mg/kg/day) or FK506 (0.3, 1, 3 mg/kg/day) suppressed the allograft rejection. In addition, topical instillation of FK506 (0.3%) was effective to prolong the graft survival as long as the topical therapy continued.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1283053", "title": "[Prostatic specific antigen (PA) in mass screening for prostate cancer].", "content": "The usefulness of prostatic specific antigen (PA) was compared with that of prostatic acid phosphatase (PAP). PA was determined in the serum of 2,183 patient examined by the mass screening for prostate cancer from 1987 to 1990. The serum samples of these patients were obtained from our serum bank. PA was measured by the E test \"TOSOH\" II (PA). The relationship of PA and PAP to prostate size estimated by digital rectal examination (DRE) and ultrasound tomography (US), and age was investigated. PA and PAP correlated with aging and prostate size estimated by DRE. However PA was more apparently related with these things. The correlation between PA and prostatic size estimated by US was relatively high (r = 0.53), but the correlation between PAP and prostate size estimated by US was low (r = 0.20). When the upper limit of normal range was set at 6.0 ng/ml, the sensitivity, specificity and efficiency was 64%, 97% and 62%, respectively. PA was more sensitive than PAP and could be more useful since none of the patients with prostate cancer was PAP positive and PA negative. We conclude that PA should be a reliable tumor marker in our mass screening system.", "contents": "[Prostatic specific antigen (PA) in mass screening for prostate cancer]. The usefulness of prostatic specific antigen (PA) was compared with that of prostatic acid phosphatase (PAP). PA was determined in the serum of 2,183 patient examined by the mass screening for prostate cancer from 1987 to 1990. The serum samples of these patients were obtained from our serum bank. PA was measured by the E test \"TOSOH\" II (PA). The relationship of PA and PAP to prostate size estimated by digital rectal examination (DRE) and ultrasound tomography (US), and age was investigated. PA and PAP correlated with aging and prostate size estimated by DRE. However PA was more apparently related with these things. The correlation between PA and prostatic size estimated by US was relatively high (r = 0.53), but the correlation between PAP and prostate size estimated by US was low (r = 0.20). When the upper limit of normal range was set at 6.0 ng/ml, the sensitivity, specificity and efficiency was 64%, 97% and 62%, respectively. PA was more sensitive than PAP and could be more useful since none of the patients with prostate cancer was PAP positive and PA negative. We conclude that PA should be a reliable tumor marker in our mass screening system."} {"id": "PMID:1283055", "title": "Papillary cystic tumor of the pancreas. A clinicopathologic study of 20 cases with cytologic, immunohistochemical, ultrastructural, and flow cytometric observations, and a review of the literature.", "content": "Twenty cases of papillary cystic tumor of the pancreas were studied (19 female patients, one male patient; median age, 19.5 years). Most tumors developed in the head or body of the pancreas as well-circumscribed, large masses. Gross examination showed that they were solid, cystic, and hemorrhagic. Preoperative fine-needle aspiration biopsy anticipated the diagnosis in four cases. Histologic examination showed that uniform cells formed solid sheets, and loss of cohesion produced pseudopapillae. Hemorrhage, foam cells, cholesterol granulomas, and entrapped nests of pancreatic parenchyma were often found. Fifteen cases studied immunohistochemically were reactive for vimentin and alpha-1-antitrypsin, 13 expressed neuron-specific enolase, 2 expressed cytokeratin, and 1 expressed S-100 protein. None were reactive for pancreatic hormones, opioid peptides, hormonal receptors, or neuroendocrine markers. Electron microscopic examination in five cases showed oval nuclei, moderate amounts of rough endoplasmic reticulum, and many mitochondria; it also showed that annulate lamellae were common. No diagnostic secretory granules were found. DNA study in nine cases revealed a diploid GO/1 peak in eight and hyperdiploid (diploid index = 1.1) DNA content in one case. Fourteen patients with follow-up were free of disease (mean, 2.6 years). Papillary cystic tumor of the pancreas possibly originates from primordial pancreatic cells and lacks definite evidence of endocrine or exocrine differentiation.", "contents": "Papillary cystic tumor of the pancreas. A clinicopathologic study of 20 cases with cytologic, immunohistochemical, ultrastructural, and flow cytometric observations, and a review of the literature. Twenty cases of papillary cystic tumor of the pancreas were studied (19 female patients, one male patient; median age, 19.5 years). Most tumors developed in the head or body of the pancreas as well-circumscribed, large masses. Gross examination showed that they were solid, cystic, and hemorrhagic. Preoperative fine-needle aspiration biopsy anticipated the diagnosis in four cases. Histologic examination showed that uniform cells formed solid sheets, and loss of cohesion produced pseudopapillae. Hemorrhage, foam cells, cholesterol granulomas, and entrapped nests of pancreatic parenchyma were often found. Fifteen cases studied immunohistochemically were reactive for vimentin and alpha-1-antitrypsin, 13 expressed neuron-specific enolase, 2 expressed cytokeratin, and 1 expressed S-100 protein. None were reactive for pancreatic hormones, opioid peptides, hormonal receptors, or neuroendocrine markers. Electron microscopic examination in five cases showed oval nuclei, moderate amounts of rough endoplasmic reticulum, and many mitochondria; it also showed that annulate lamellae were common. No diagnostic secretory granules were found. DNA study in nine cases revealed a diploid GO/1 peak in eight and hyperdiploid (diploid index = 1.1) DNA content in one case. Fourteen patients with follow-up were free of disease (mean, 2.6 years). Papillary cystic tumor of the pancreas possibly originates from primordial pancreatic cells and lacks definite evidence of endocrine or exocrine differentiation."} {"id": "PMID:1283056", "title": "Study of the major phenotype of large granular T-cell lymphoproliferative disorder.", "content": "Six cases of large granular T-cell lymphoproliferative disorder with a selected immunophenotype (CD3+, CD4-, CD8+, CD16+) were studied to characterize a homogeneous group of patients. It was found that most of these patients did not exhibit the clinical features frequently described in large granular T-cell lymphoproliferative disorder--recurrent infection, rheumatoid arthritis, and splenomegaly. The laboratory tests usually positive in large granular T-cell lymphoproliferative disorder, including rheumatoid factor and anti-nuclear antibodies, also were frequently negative. The pathognomonic features were found to be neutropenia and large granular lymphocytosis with positive killer cell markers. All six cases showed T-cell receptor gene rearrangement that indicated a monoclonal proliferation of lymphoid cells, which were natural killer-like T cells by immunophenotyping. B cells were essentially absent in all cases. It should be emphasized that bone marrow aspirates are as informative as peripheral blood samples for the diagnosis of large granular T-cell lymphoproliferative disorder; indeed, phenotypes of blood and marrow in one case were identical in terms of percentages of markers. In this selected group of patients, the clinical courses were indolent with uncomplicated outcomes. In three patients, chemotherapy did not induce an obvious clinical response, but all patients' conditions remained stable with only supportive care.", "contents": "Study of the major phenotype of large granular T-cell lymphoproliferative disorder. Six cases of large granular T-cell lymphoproliferative disorder with a selected immunophenotype (CD3+, CD4-, CD8+, CD16+) were studied to characterize a homogeneous group of patients. It was found that most of these patients did not exhibit the clinical features frequently described in large granular T-cell lymphoproliferative disorder--recurrent infection, rheumatoid arthritis, and splenomegaly. The laboratory tests usually positive in large granular T-cell lymphoproliferative disorder, including rheumatoid factor and anti-nuclear antibodies, also were frequently negative. The pathognomonic features were found to be neutropenia and large granular lymphocytosis with positive killer cell markers. All six cases showed T-cell receptor gene rearrangement that indicated a monoclonal proliferation of lymphoid cells, which were natural killer-like T cells by immunophenotyping. B cells were essentially absent in all cases. It should be emphasized that bone marrow aspirates are as informative as peripheral blood samples for the diagnosis of large granular T-cell lymphoproliferative disorder; indeed, phenotypes of blood and marrow in one case were identical in terms of percentages of markers. In this selected group of patients, the clinical courses were indolent with uncomplicated outcomes. In three patients, chemotherapy did not induce an obvious clinical response, but all patients' conditions remained stable with only supportive care."} {"id": "PMID:1283054", "title": "Treatment of perennial allergic rhinitis with cetirizine.", "content": "A study was made of 30 patients with perennial extrinsic rhinitis sensitized only to dust mites who were treated with cetirizine for 15 days, at a dose of 10 mg/24 hours. The following parameters were evaluated in each patient on day -1 before initiating treatment and on day 15: histamine 1/100 prick-test, Dermatohophagoides pteronyssinus prick-test, physical examination, assessment of nasal edema and rhinorrhea by anterior rhinoscopy, and of the degree of nasal obstruction by active anterior rhinomanometry. Each patient was given a form for daily clinical self-evaluation of the following subjective symptoms: sneezing, rhinorrhea, nasal obstruction, and nasal itchiness. The occurrence of side effects was evaluated. Cetirizine reduced significantly the area of the histamine and D. pteronyssinus papules elicited by prick-test. Clinical symptoms decreased significantly, with sneezing, nasal itchiness and rhinorrhea being greatly relieved, and nasal obstruction, evaluated by means of active anterior rhinomanometry performed before and after 15 days of treatment, being less alleviated. There was scant incidence of side effects in patients treated with cetirizine.", "contents": "Treatment of perennial allergic rhinitis with cetirizine. A study was made of 30 patients with perennial extrinsic rhinitis sensitized only to dust mites who were treated with cetirizine for 15 days, at a dose of 10 mg/24 hours. The following parameters were evaluated in each patient on day -1 before initiating treatment and on day 15: histamine 1/100 prick-test, Dermatohophagoides pteronyssinus prick-test, physical examination, assessment of nasal edema and rhinorrhea by anterior rhinoscopy, and of the degree of nasal obstruction by active anterior rhinomanometry. Each patient was given a form for daily clinical self-evaluation of the following subjective symptoms: sneezing, rhinorrhea, nasal obstruction, and nasal itchiness. The occurrence of side effects was evaluated. Cetirizine reduced significantly the area of the histamine and D. pteronyssinus papules elicited by prick-test. Clinical symptoms decreased significantly, with sneezing, nasal itchiness and rhinorrhea being greatly relieved, and nasal obstruction, evaluated by means of active anterior rhinomanometry performed before and after 15 days of treatment, being less alleviated. There was scant incidence of side effects in patients treated with cetirizine."} {"id": "PMID:1283057", "title": "Hand mirror variant of adult acute lymphoblastic leukemia. Evidence for a mixed leukemia.", "content": "Blast cells from a female patient with acute lymphoblastic leukemia-hand mirror variant were examined using various techniques, including light and ultrastructural morphologic examination, cytochemical analysis, surface antigen characterization, cytogenetic analysis, and gene rearrangement studies. The blast cells were found to be pre-B cells (CD19+ and Tdt+) that also expressed the myeloid antigens CD13 and CD33 and demonstrated a heavy chain immunoglobulin gene rearrangement. Cytogenetic studies revealed a t(11;19) translocation previously described in biphenotypic leukemias. A subset of acute lymphoblastic leukemia-hand mirror cells has been previously defined and includes predominately female patients with an indolent course. The authors' findings place this case, a mixed leukemia, within that subgroup. The possibility of mixed lineage should be considered in future cases of hand mirror variants of adult acute lymphoblastic leukemia. Furthermore, hand mirror morphologic features in any case of acute leukemia should alert the hematopathologist/hematologist to the possibility of mixed lineage.", "contents": "Hand mirror variant of adult acute lymphoblastic leukemia. Evidence for a mixed leukemia. Blast cells from a female patient with acute lymphoblastic leukemia-hand mirror variant were examined using various techniques, including light and ultrastructural morphologic examination, cytochemical analysis, surface antigen characterization, cytogenetic analysis, and gene rearrangement studies. The blast cells were found to be pre-B cells (CD19+ and Tdt+) that also expressed the myeloid antigens CD13 and CD33 and demonstrated a heavy chain immunoglobulin gene rearrangement. Cytogenetic studies revealed a t(11;19) translocation previously described in biphenotypic leukemias. A subset of acute lymphoblastic leukemia-hand mirror cells has been previously defined and includes predominately female patients with an indolent course. The authors' findings place this case, a mixed leukemia, within that subgroup. The possibility of mixed lineage should be considered in future cases of hand mirror variants of adult acute lymphoblastic leukemia. Furthermore, hand mirror morphologic features in any case of acute leukemia should alert the hematopathologist/hematologist to the possibility of mixed lineage."} {"id": "PMID:1283059", "title": "Assessment of histamine release from basophils in whole blood by benzylpenicilloyl poly-L-lysine in penicillin-sensitized patients.", "content": "Histamine release from basophil granulocytes in whole blood by benzylpenicilloyl poly-L-lysine (PPL) was investigated in 7 patients with penicillin allergy. All patients presented with systemic immediate hypersensitivity reactions after i.v. administration of penicillin G. Total histamine (of 7 patients) ranged from 27.5 ng/ml to 62.1 ng/ml (mean 43.2 ng/ml). The spontaneous histamine release ranged from 0.15% to 5.1% (mean 1.8%) of the total content. Addition of PPL in various concentrations resulted in values between 0.8 and 9.6%. Although PPL is a reliable allergen for prick- and intradermal testing in the diagnosis of penicillin allergy--demonstrating a histamine liberation in the skin--the in vitro experiment using the same allergen showed no histamine release above 10%. Using a threshold of 5% out of 7 patients, 4 (57%) would show a positive histamine release. Therefore it might indicate that in penicillin allergy a threshold of 5% must be used. In addition, basophils in whole blood and skin mast cells may be activated differently.", "contents": "Assessment of histamine release from basophils in whole blood by benzylpenicilloyl poly-L-lysine in penicillin-sensitized patients. Histamine release from basophil granulocytes in whole blood by benzylpenicilloyl poly-L-lysine (PPL) was investigated in 7 patients with penicillin allergy. All patients presented with systemic immediate hypersensitivity reactions after i.v. administration of penicillin G. Total histamine (of 7 patients) ranged from 27.5 ng/ml to 62.1 ng/ml (mean 43.2 ng/ml). The spontaneous histamine release ranged from 0.15% to 5.1% (mean 1.8%) of the total content. Addition of PPL in various concentrations resulted in values between 0.8 and 9.6%. Although PPL is a reliable allergen for prick- and intradermal testing in the diagnosis of penicillin allergy--demonstrating a histamine liberation in the skin--the in vitro experiment using the same allergen showed no histamine release above 10%. Using a threshold of 5% out of 7 patients, 4 (57%) would show a positive histamine release. Therefore it might indicate that in penicillin allergy a threshold of 5% must be used. In addition, basophils in whole blood and skin mast cells may be activated differently."} {"id": "PMID:1283060", "title": "Clinical evaluation of in vitro leukocyte histamine release in allergy to muscle relaxant drugs.", "content": "We have evaluated the in vitro leukocyte histamine release tests for the diagnosis of allergy to muscle relaxant drugs in 40 patients (Group A) and a control group of 44 subjects with negative leukocyte histamine release (Group B). Non-IgE dependent histamine release, expressed as a percentage of the total blood histamine, was 3.94% +/- 0.49 in Group B. The upper limit of positivity was estimated to be 5% (mean + 2 SD). Leukocyte histamine release tests were positive in 65% of the patients from Group A. The concordance between LHR and QAS-RIA was 64%. The maximal histamine release was observed at dilutions of 10(-2)-10(-4) in 20 of the 26 positive cases. The maximal histamine release was 43.8% +/- 23.3. The spontaneous histamine release was as low as 1.7% +/- 1.1. Cross-reactivity among the 5 different muscle relaxant drugs has been investigated and compared by intradermal testing. The muscle relaxant drugs which gave the lower skin reaction (M2) and the drug responsible for shock (M1) were selected for the study of in vitro leukocyte histamine release. Of 20 M2. All of the 10 cases had negative ID tests with M2. Three of these patients subsequently underwent general anesthesia with the muscle relaxant chosen as harmless (M2) without any clinical reaction.", "contents": "Clinical evaluation of in vitro leukocyte histamine release in allergy to muscle relaxant drugs. We have evaluated the in vitro leukocyte histamine release tests for the diagnosis of allergy to muscle relaxant drugs in 40 patients (Group A) and a control group of 44 subjects with negative leukocyte histamine release (Group B). Non-IgE dependent histamine release, expressed as a percentage of the total blood histamine, was 3.94% +/- 0.49 in Group B. The upper limit of positivity was estimated to be 5% (mean + 2 SD). Leukocyte histamine release tests were positive in 65% of the patients from Group A. The concordance between LHR and QAS-RIA was 64%. The maximal histamine release was observed at dilutions of 10(-2)-10(-4) in 20 of the 26 positive cases. The maximal histamine release was 43.8% +/- 23.3. The spontaneous histamine release was as low as 1.7% +/- 1.1. Cross-reactivity among the 5 different muscle relaxant drugs has been investigated and compared by intradermal testing. The muscle relaxant drugs which gave the lower skin reaction (M2) and the drug responsible for shock (M1) were selected for the study of in vitro leukocyte histamine release. Of 20 M2. All of the 10 cases had negative ID tests with M2. Three of these patients subsequently underwent general anesthesia with the muscle relaxant chosen as harmless (M2) without any clinical reaction."} {"id": "PMID:1283061", "title": "Egg and milk allergy in adults. Diagnosis and characterization.", "content": "Nineteen adult patients representing a total of 24 medical histories of immediate adverse reactions to egg or cows' milk underwent 1) standardized questioning about signs/symptoms occurring less than 2 h after ingestion of egg or milk, 2) skin prick test, RAST and histamine release test, and 3) titrated, oral, double-blind, placebo-controlled challenge (DBPCFC) with fresh egg or milk. Eleven medical histories (46%) were confirmed by DBPCFC in 10 patients (53%). All DBPCFC-positive patients experienced gastrointestinal symptoms, and in 80% of the patients, gastrointestinal symptoms were accompanied by respiratory or skin symptoms. Threshold doses varied between 50 mg and 250 g, with 4 patients presenting objective signs following 5 g or less. DBPCFC-positive patients reported significantly more symptoms and had a significantly higher number of positive tests than had DBPCFC-negative patients. None of the tests were in significant concordance with DBPCFC, although RAST showed a sensitivity of 100%. Thus, DBPCFC cannot be substituted in the diagnosis of milk and egg allergy in adults. The use of titrated, fresh foods in DBPCFC proved to be a safe and well-controlled procedure.", "contents": "Egg and milk allergy in adults. Diagnosis and characterization. Nineteen adult patients representing a total of 24 medical histories of immediate adverse reactions to egg or cows' milk underwent 1) standardized questioning about signs/symptoms occurring less than 2 h after ingestion of egg or milk, 2) skin prick test, RAST and histamine release test, and 3) titrated, oral, double-blind, placebo-controlled challenge (DBPCFC) with fresh egg or milk. Eleven medical histories (46%) were confirmed by DBPCFC in 10 patients (53%). All DBPCFC-positive patients experienced gastrointestinal symptoms, and in 80% of the patients, gastrointestinal symptoms were accompanied by respiratory or skin symptoms. Threshold doses varied between 50 mg and 250 g, with 4 patients presenting objective signs following 5 g or less. DBPCFC-positive patients reported significantly more symptoms and had a significantly higher number of positive tests than had DBPCFC-negative patients. None of the tests were in significant concordance with DBPCFC, although RAST showed a sensitivity of 100%. Thus, DBPCFC cannot be substituted in the diagnosis of milk and egg allergy in adults. The use of titrated, fresh foods in DBPCFC proved to be a safe and well-controlled procedure."} {"id": "PMID:1283062", "title": "Analysis of antigenic determinants shared by two different allergens recognized by human T cells: house dust mite (Dermatophagoides pteronyssinus) and chironomid midge (Chironomus yoshimatsui).", "content": "To analyse the cross-reactivity of T-cell-mediated immunity between Dermatophagoides pteronyssinus (Dp) and Chironomus yoshimatsui (Cy), the most common allergens in Japan, we established antigen-specific human T-cell lines and clones. Some but not all of the Cy-induced T-cell lines showed a significant proliferative response not only to Cy, but also to Dp. No T-cell line responded to other unrelated antigens. When we stimulated the Dp-induced T-cell clones with Cy, 3 of the 40 clones (7.5%) showed a significant proliferation, and 2 of the 3 clones produced interleukin-4 and interferon-gamma, indicating their helper function. Cross-reactivity was diminished significantly after the absorption of Dp antigen in an anti-Cy affinity column. The cross-reactive epitopes were thought to be expressed on the Dp molecule of 45-53 kD. The presence of helper T cells reactive to both allergens suggests a possibility that this cross-reactivity might be involved in part in the high incidence of allergy to the 2 major allergens.", "contents": "Analysis of antigenic determinants shared by two different allergens recognized by human T cells: house dust mite (Dermatophagoides pteronyssinus) and chironomid midge (Chironomus yoshimatsui). To analyse the cross-reactivity of T-cell-mediated immunity between Dermatophagoides pteronyssinus (Dp) and Chironomus yoshimatsui (Cy), the most common allergens in Japan, we established antigen-specific human T-cell lines and clones. Some but not all of the Cy-induced T-cell lines showed a significant proliferative response not only to Cy, but also to Dp. No T-cell line responded to other unrelated antigens. When we stimulated the Dp-induced T-cell clones with Cy, 3 of the 40 clones (7.5%) showed a significant proliferation, and 2 of the 3 clones produced interleukin-4 and interferon-gamma, indicating their helper function. Cross-reactivity was diminished significantly after the absorption of Dp antigen in an anti-Cy affinity column. The cross-reactive epitopes were thought to be expressed on the Dp molecule of 45-53 kD. The presence of helper T cells reactive to both allergens suggests a possibility that this cross-reactivity might be involved in part in the high incidence of allergy to the 2 major allergens."} {"id": "PMID:1283064", "title": "Transcriptional inhibition by carcinogenic chromate: relationship to DNA damage.", "content": "Hexavalent chromium compounds are carcinogenic to humans, are potent inducers of tumors in experimental animals, and can neoplastically transform cells in culture. In this study, the effects of sodium chromate on the expression of the 78-kDa glucose-regulated protein (GRP78) gene and on general transcription were investigated with respect to the DNA damage induced by this agent. DNA single-strand breaks, DNA-protein cross-links, and chromium-DNA adducts were present in CHO cells immediately after 2 h of treatment with sodium chromate. Subsequently, these types of damage were repaired at different rates. Single-strand breaks were essentially repaired after 8 h. By 24 h posttreatment, no cross-links remained in cells exposed to 30 or 150 microM chromate, although cells treated with the 300-microM concentration still contained cross-links at that time. DNA-chromium adducts remained unrepaired for at least 32 h. The moderate constitutive level of GRP78 mRNA was not affected by chromate. Chromate did, however, suppress induction of this gene by tunicamycin in a concentration-and time-dependent manner. Thirty micromolar sodium chromate (96% survival), which caused the least DNA damage, had no effect on GRP78 induction, general RNA synthesis, or mRNA synthesis. Induction of GRP78 was suppressed immediately and 12 h after treatment with 150 microM chromate (54% survival), although there was a partial recovery of induction at 24 h after treatment, which correlated with the repair of DNA-protein cross-links. In contrast, both total cytoplasmic RNA and mRNA synthesis were suppressed by approximately 60-75% for at least 32 h by 150 microM chromate. At the 300-microM concentration (8% survival), where DNA-protein cross-links persisted beyond 24 h, GRP78 induction was totally suppressed for at least 24 h, while total RNA and mRNA synthesis were suppressed by 80-90% for at least 32 h. Overall, the effects of chromate on GRP78 induction correlated most closely with the presence of DNA-protein cross-links, but suppression of total RNA and mRNA synthesis correlated with the presence of DNA-chromium adducts. These results indicate that chromate exerts differential effects on the induction of the GRP78 gene and on general transcription.", "contents": "Transcriptional inhibition by carcinogenic chromate: relationship to DNA damage. Hexavalent chromium compounds are carcinogenic to humans, are potent inducers of tumors in experimental animals, and can neoplastically transform cells in culture. In this study, the effects of sodium chromate on the expression of the 78-kDa glucose-regulated protein (GRP78) gene and on general transcription were investigated with respect to the DNA damage induced by this agent. DNA single-strand breaks, DNA-protein cross-links, and chromium-DNA adducts were present in CHO cells immediately after 2 h of treatment with sodium chromate. Subsequently, these types of damage were repaired at different rates. Single-strand breaks were essentially repaired after 8 h. By 24 h posttreatment, no cross-links remained in cells exposed to 30 or 150 microM chromate, although cells treated with the 300-microM concentration still contained cross-links at that time. DNA-chromium adducts remained unrepaired for at least 32 h. The moderate constitutive level of GRP78 mRNA was not affected by chromate. Chromate did, however, suppress induction of this gene by tunicamycin in a concentration-and time-dependent manner. Thirty micromolar sodium chromate (96% survival), which caused the least DNA damage, had no effect on GRP78 induction, general RNA synthesis, or mRNA synthesis. Induction of GRP78 was suppressed immediately and 12 h after treatment with 150 microM chromate (54% survival), although there was a partial recovery of induction at 24 h after treatment, which correlated with the repair of DNA-protein cross-links. In contrast, both total cytoplasmic RNA and mRNA synthesis were suppressed by approximately 60-75% for at least 32 h by 150 microM chromate. At the 300-microM concentration (8% survival), where DNA-protein cross-links persisted beyond 24 h, GRP78 induction was totally suppressed for at least 24 h, while total RNA and mRNA synthesis were suppressed by 80-90% for at least 32 h. Overall, the effects of chromate on GRP78 induction correlated most closely with the presence of DNA-protein cross-links, but suppression of total RNA and mRNA synthesis correlated with the presence of DNA-chromium adducts. These results indicate that chromate exerts differential effects on the induction of the GRP78 gene and on general transcription."} {"id": "PMID:1283065", "title": "Regulatory mutations and human genetic disease.", "content": "Mutations in gene promoter/regulatory regions represent an important class of lesion causing human genetic disease. Such mutations are associated with either increases or decreases in transcriptional activity mediated by the altered binding behaviour of trans-acting protein factors to specific DNA sequences in the promoter region. Although most promoter mutations are individually very infrequent, some occur at polymorphic frequencies. Both categories of lesion are likely to be important in clinical medicine and their study has already led to new insights into the mechanisms underlying the regulation of human genes.", "contents": "Regulatory mutations and human genetic disease. Mutations in gene promoter/regulatory regions represent an important class of lesion causing human genetic disease. Such mutations are associated with either increases or decreases in transcriptional activity mediated by the altered binding behaviour of trans-acting protein factors to specific DNA sequences in the promoter region. Although most promoter mutations are individually very infrequent, some occur at polymorphic frequencies. Both categories of lesion are likely to be important in clinical medicine and their study has already led to new insights into the mechanisms underlying the regulation of human genes."} {"id": "PMID:1283075", "title": "[Treatment of chronic non-A, non-B-C hepatitis].", "content": "Preventive measures, and particularly screening for anti-HCV donors, have diminished the incidence of HCV infections, however, a vaccine against the disease is necessary for an effective prevention. The most active treatment at this time, seems to be alpha-interferon, at the dosage of 3 MU during 6 months. Possibly larger doses during longer periods of time might improve response and recurrence indexes, but not sufficiently as to give indiscriminate treatment to all patients at great cost and with many adverse reactions. While waiting for better predictive factors, the most convenient therapy remains the indicated dosage during 6 months, followed by periodic assessment during 2-3 months of transaminase levels: if they remain normal, the patient should be reassessed later on, if there is a recurrence, another course of treatment should be tried; non-responders should not be treated again with single interferon; other combinations or different treatments should be tried.", "contents": "[Treatment of chronic non-A, non-B-C hepatitis]. Preventive measures, and particularly screening for anti-HCV donors, have diminished the incidence of HCV infections, however, a vaccine against the disease is necessary for an effective prevention. The most active treatment at this time, seems to be alpha-interferon, at the dosage of 3 MU during 6 months. Possibly larger doses during longer periods of time might improve response and recurrence indexes, but not sufficiently as to give indiscriminate treatment to all patients at great cost and with many adverse reactions. While waiting for better predictive factors, the most convenient therapy remains the indicated dosage during 6 months, followed by periodic assessment during 2-3 months of transaminase levels: if they remain normal, the patient should be reassessed later on, if there is a recurrence, another course of treatment should be tried; non-responders should not be treated again with single interferon; other combinations or different treatments should be tried."} {"id": "PMID:1283076", "title": "Simulation of animal cell metabolism.", "content": "A simulation of hybridoma growth and antibody production has been developed. It is capable of simulating all major variables of interest (e.g., specific growth rate, cell yield, sugars and amino acids profile, and antibody yield). This simulation is the most complete reported to date including such factors as cell composition, media composition, substrate and product effects, osmolarity etc. The stimulation of a large range of experimental data for hybridomas illustrates that this simulation is a powerful tool in the rational assessment of factors influencing the growth and metabolism of hybridoma cells.", "contents": "Simulation of animal cell metabolism. A simulation of hybridoma growth and antibody production has been developed. It is capable of simulating all major variables of interest (e.g., specific growth rate, cell yield, sugars and amino acids profile, and antibody yield). This simulation is the most complete reported to date including such factors as cell composition, media composition, substrate and product effects, osmolarity etc. The stimulation of a large range of experimental data for hybridomas illustrates that this simulation is a powerful tool in the rational assessment of factors influencing the growth and metabolism of hybridoma cells."} {"id": "PMID:1283077", "title": "Biological characteristics of CD7 positive acute myelogenous leukaemia.", "content": "We studied the biological characteristics of CD7+ acute myelogenous leukaemia (AML). We diagnosed nine out of 88 consecutive AML cases as CD7+ AML based on myeloperoxidase positivity and surface antigen expression. In eight of these nine cases more than 20% of leukaemic blasts were found to coexpress both CD7 and a myeloid-associated antigen, CD33, by a two-colour flow-cytometric assay, while in the remaining case more than 90% of blasts were positive for CD7 and myeloperoxidase. CD7+ AML was most frequently observed in M1 among AML subtypes according to the FAB classification. An early stage-specific antigen, CD34 was also expressed on leukaemic blasts from eight of these nine cases. Neither the T-cell receptor (TcR)-beta nor the TcR-gamma gene was clonally rearranged in any of the cases. We then studied the proliferative responses to stimulation by various growth factors. Among interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF), IL-3 showed the strongest stimulatory effect on DNA synthesis and leukaemic blast colony formation in 8/9 and 6/8 CD7+ AML cases examined, respectively. On the other hand, the strongest stimulatory effect exerted by IL-3 on blast colony formation was observed in only six out of the 33 CD7- AML cases examined. Furthermore, CD7+ AML blasts could proliferate in response to stem cell factor (SCF); SCF alone showed stimulatory effects on blast colony formation (7/8 cases), and in 5/7 SCF-responding cases, stimulatory effects of SCF were more potent than those of IL-3. In addition, SCF enhanced blast colony formation synergistically with IL-3 in four of these seven cases. These data suggest that progenitor cells of CD7+ AML may possess the biological properties characteristic of immature haematopoietic stem cells.", "contents": "Biological characteristics of CD7 positive acute myelogenous leukaemia. We studied the biological characteristics of CD7+ acute myelogenous leukaemia (AML). We diagnosed nine out of 88 consecutive AML cases as CD7+ AML based on myeloperoxidase positivity and surface antigen expression. In eight of these nine cases more than 20% of leukaemic blasts were found to coexpress both CD7 and a myeloid-associated antigen, CD33, by a two-colour flow-cytometric assay, while in the remaining case more than 90% of blasts were positive for CD7 and myeloperoxidase. CD7+ AML was most frequently observed in M1 among AML subtypes according to the FAB classification. An early stage-specific antigen, CD34 was also expressed on leukaemic blasts from eight of these nine cases. Neither the T-cell receptor (TcR)-beta nor the TcR-gamma gene was clonally rearranged in any of the cases. We then studied the proliferative responses to stimulation by various growth factors. Among interleukin-3 (IL-3), granulocyte/macrophage colony-stimulating factor (GM-CSF), and granulocyte-CSF (G-CSF), IL-3 showed the strongest stimulatory effect on DNA synthesis and leukaemic blast colony formation in 8/9 and 6/8 CD7+ AML cases examined, respectively. On the other hand, the strongest stimulatory effect exerted by IL-3 on blast colony formation was observed in only six out of the 33 CD7- AML cases examined. Furthermore, CD7+ AML blasts could proliferate in response to stem cell factor (SCF); SCF alone showed stimulatory effects on blast colony formation (7/8 cases), and in 5/7 SCF-responding cases, stimulatory effects of SCF were more potent than those of IL-3. In addition, SCF enhanced blast colony formation synergistically with IL-3 in four of these seven cases. These data suggest that progenitor cells of CD7+ AML may possess the biological properties characteristic of immature haematopoietic stem cells."} {"id": "PMID:1283078", "title": "Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases.", "content": "Lymphadenopathy is an uncommon finding in hairy cell leukaemia (HCL). We report 12 HCL patients in whom relapse was associated with massive abdominal lymphadenopathy. All but one had long-standing HCL (range 3-25 years; median 10 years); in one it was discovered at presentation. Nine patients had been splenectomized and seven had previously been treated with 2'deoxycoformycin (DCF) and/or alpha-interferon (alpha IFN): three had achieved complete remission and four a partial response. The computerized tomography (CT) scan appearances were similar in all cases with a primary lymph node mass centred around the coeliac axis and involving upper para-aortic and retropancreatic regions. Histology and/or cytology confirmed nodal involvement by HCL in six patients. Large immature hairy cells were seen in both lymph nodes and bone marrow, suggesting a degree of transformation. Nine patients were treated with DCF: one had complete resolution, six responded with 50-90% reduction of the lymphadenopathy, one did not respond and one is still on treatment; alpha-IFN was used concomitantly or sequentially in two of the responders. One responding patient died of sepsis after four injections of DCF. Three patients received either alpha- or beta-IFN alone with no response. One elderly patient was not treated. Abdominal lymphadenopathy could be part of the natural history of HCL and/or may represent a transformation analogous to that seen in other low-grade lymphoproliferative disorders. Routine abdominal CT scanning should be part of the work up of all patients with HCL.", "contents": "Massive abdominal lymphadenopathy in hairy cell leukaemia: a report of 12 cases. Lymphadenopathy is an uncommon finding in hairy cell leukaemia (HCL). We report 12 HCL patients in whom relapse was associated with massive abdominal lymphadenopathy. All but one had long-standing HCL (range 3-25 years; median 10 years); in one it was discovered at presentation. Nine patients had been splenectomized and seven had previously been treated with 2'deoxycoformycin (DCF) and/or alpha-interferon (alpha IFN): three had achieved complete remission and four a partial response. The computerized tomography (CT) scan appearances were similar in all cases with a primary lymph node mass centred around the coeliac axis and involving upper para-aortic and retropancreatic regions. Histology and/or cytology confirmed nodal involvement by HCL in six patients. Large immature hairy cells were seen in both lymph nodes and bone marrow, suggesting a degree of transformation. Nine patients were treated with DCF: one had complete resolution, six responded with 50-90% reduction of the lymphadenopathy, one did not respond and one is still on treatment; alpha-IFN was used concomitantly or sequentially in two of the responders. One responding patient died of sepsis after four injections of DCF. Three patients received either alpha- or beta-IFN alone with no response. One elderly patient was not treated. Abdominal lymphadenopathy could be part of the natural history of HCL and/or may represent a transformation analogous to that seen in other low-grade lymphoproliferative disorders. Routine abdominal CT scanning should be part of the work up of all patients with HCL."} {"id": "PMID:1283079", "title": "Mouse erythrocyte rosette formation with malignant human B-lymphocytes re-evaluated: still a useful marker for differentiating mature B-cell malignancies.", "content": "We have re-evaluated mouse rosette formation (MRF) as a marker for B-CLL by estimating the fraction of mouse rosette forming B-lymphocytes (identified by CD20 monoclonal antibodies) in normal donors and malignant CD20+ cell proliferations (ALL, AML, B-NHL, B-HCL and B-CLL). Whereas this ratio was increased in B-CLL, all other CD20 positive malignancies showed mean ratios of less than 0.1. As part of a Danish multi-centre study, we furthermore prospectively analysed 86 patients and found that the mouse/CD20 ratio divided the 78 patients with monoclonal B-cell populations suspected of B-CLL in two distinct groups. In the low ratio group, three patients were categorized as leukaemized B-NHL and one as PLL. The remaining three patients with low ratio were clinically and immunologically (by SmIg density and CD5 expression) B-CLL patients suggesting a frequency of MR-negative B-CLLs of approximately 5%. In the high ratio group two of 70 patients were diagnosed as B-NHLs. Thirdly, MRF was a valuable parameter in patients, where transformation of disease is suspected, since it preceded clinical changes by several months. Thus, MRF is still a useful marker in the age of monoclonal antibodies.", "contents": "Mouse erythrocyte rosette formation with malignant human B-lymphocytes re-evaluated: still a useful marker for differentiating mature B-cell malignancies. We have re-evaluated mouse rosette formation (MRF) as a marker for B-CLL by estimating the fraction of mouse rosette forming B-lymphocytes (identified by CD20 monoclonal antibodies) in normal donors and malignant CD20+ cell proliferations (ALL, AML, B-NHL, B-HCL and B-CLL). Whereas this ratio was increased in B-CLL, all other CD20 positive malignancies showed mean ratios of less than 0.1. As part of a Danish multi-centre study, we furthermore prospectively analysed 86 patients and found that the mouse/CD20 ratio divided the 78 patients with monoclonal B-cell populations suspected of B-CLL in two distinct groups. In the low ratio group, three patients were categorized as leukaemized B-NHL and one as PLL. The remaining three patients with low ratio were clinically and immunologically (by SmIg density and CD5 expression) B-CLL patients suggesting a frequency of MR-negative B-CLLs of approximately 5%. In the high ratio group two of 70 patients were diagnosed as B-NHLs. Thirdly, MRF was a valuable parameter in patients, where transformation of disease is suspected, since it preceded clinical changes by several months. Thus, MRF is still a useful marker in the age of monoclonal antibodies."} {"id": "PMID:1283080", "title": "Studies of oral neutrophil levels in patients receiving G-CSF after autologous marrow transplantation.", "content": "Patients are at risk of mucositis and infections in the oral cavity during the neutropenic period after chemotherapy, which are significant causes of morbidity. In phase I/II studies with the haemopoietic growth factor granulocyte colony stimulating factor (G-CSF), a reduction in post-chemotherapy mucositis has been observed in addition to haematologic effects. To understand this phenomenon better in patients receiving G-CSF following high-dose chemotherapy with autologous bone marrow transplantation (ABMT), we studied the effects of G-CSF on levels of neutrophils recoverable from the oral cavity using a quantitative mouthrinse assay. In normal subjects, mouthrinses contained 472 +/- 329 x 10(3) neutrophils/mouthrinse. After chemotherapy followed by ABMT, mouthrinse neutrophil levels decreased to undetectable levels during the neutropenic period, but recovered 1-2 and 3-9 d before circulating neutrophil levels reached 0.1 and 1 x 10(9)/l respectively, whether or not patients received G-CSF. In patients who received G-CSF, the mean cumulative mucositis score was reduced from 35 +/- 9 to 21 +/- 12 (P < 0.05), and the maximum mean daily mucositis score was reduced from 2.8 +/- 0.5 to 1.7 +/- 0.9 (P < 0.01), compared to patients who did not receive G-CSF after ABMT. These studies provide in vivo evidence that neutrophils produced during G-CSF therapy are available to leave the circulation and enter tissues where their function is required for host defence. Since the usual temporal relationship between oral and peripheral blood neutrophil recovery was preserved during G-CSF administration after ABMT, these data support the hypothesis that the reduction in post-ABMT mucositis observed with G-CSF therapy may reflect a beneficial effect of G-CSF on the kinetics of oral mucosal neutrophil recovery in addition to the effect of G-CSF to accelerate peripheral blood neutrophil recovery.", "contents": "Studies of oral neutrophil levels in patients receiving G-CSF after autologous marrow transplantation. Patients are at risk of mucositis and infections in the oral cavity during the neutropenic period after chemotherapy, which are significant causes of morbidity. In phase I/II studies with the haemopoietic growth factor granulocyte colony stimulating factor (G-CSF), a reduction in post-chemotherapy mucositis has been observed in addition to haematologic effects. To understand this phenomenon better in patients receiving G-CSF following high-dose chemotherapy with autologous bone marrow transplantation (ABMT), we studied the effects of G-CSF on levels of neutrophils recoverable from the oral cavity using a quantitative mouthrinse assay. In normal subjects, mouthrinses contained 472 +/- 329 x 10(3) neutrophils/mouthrinse. After chemotherapy followed by ABMT, mouthrinse neutrophil levels decreased to undetectable levels during the neutropenic period, but recovered 1-2 and 3-9 d before circulating neutrophil levels reached 0.1 and 1 x 10(9)/l respectively, whether or not patients received G-CSF. In patients who received G-CSF, the mean cumulative mucositis score was reduced from 35 +/- 9 to 21 +/- 12 (P < 0.05), and the maximum mean daily mucositis score was reduced from 2.8 +/- 0.5 to 1.7 +/- 0.9 (P < 0.01), compared to patients who did not receive G-CSF after ABMT. These studies provide in vivo evidence that neutrophils produced during G-CSF therapy are available to leave the circulation and enter tissues where their function is required for host defence. Since the usual temporal relationship between oral and peripheral blood neutrophil recovery was preserved during G-CSF administration after ABMT, these data support the hypothesis that the reduction in post-ABMT mucositis observed with G-CSF therapy may reflect a beneficial effect of G-CSF on the kinetics of oral mucosal neutrophil recovery in addition to the effect of G-CSF to accelerate peripheral blood neutrophil recovery."} {"id": "PMID:1283081", "title": "Inhibition by heparin and derivatized dextrans of Staphylococcus aureus adhesion to fibronectin-coated biomaterials.", "content": "Recent data on cardiovascular device-centered infections suggest that some plasma and extracellular matrix proteins contribute to bacterial adhesion and colonization on biomaterials. We previously developed an in vitro assay to study the Staphylococcus aureus adhesion-promoting effect of surface-adsorbed fibronectin on flat PMMA coverslips coated with a monolayer amount of fibronectin. We screened the potential anti-adhesive properties of a group of substituted dextrans, previously shown to exhibit potent anticoagulant and anticomplementary activities. In comparison to unsubstituted dextran which showed no significant (< 20%) adhesion inhibition at 1 mg/ml, dextrans increasingly substituted with carboxylic and benzylamide groups (CMBD) exhibited increasing anti-adhesive activities. Three CMBD derivatives showing an increasing proportion (5-14%) of benzylamide groups showed inhibition of bacterial adhesion increasing from 33 to 51% at 1 mg/ml. Another category of substituted dextrans having a variable proportion (2-26%) of sulfonated benzylamide groups (CMBDS) produced active inhibition of S. aureus adhesion. In comparison to these heparin-like dextran derivatives, native heparin produced inhibition values of S. aureus adhesion which were intermediate between those of CMBD and CMBDS compounds. Furthermore, the anti-adhesive activity was still expressed when substituted dextrans were preincubated with fibronectin-coated PMMA but washed away at the time when radiolabeled bacteria were added to the adhesion assay. This indicates that the anti-adhesive effects of CMBDS could be exerted at the level of the S. aureus binding site of fibronectin. In conclusion, S. aureus adhesion on fibronectin-coated biomaterials can be efficiently blocked in vitro by soluble compounds such as dextran derivatives.", "contents": "Inhibition by heparin and derivatized dextrans of Staphylococcus aureus adhesion to fibronectin-coated biomaterials. Recent data on cardiovascular device-centered infections suggest that some plasma and extracellular matrix proteins contribute to bacterial adhesion and colonization on biomaterials. We previously developed an in vitro assay to study the Staphylococcus aureus adhesion-promoting effect of surface-adsorbed fibronectin on flat PMMA coverslips coated with a monolayer amount of fibronectin. We screened the potential anti-adhesive properties of a group of substituted dextrans, previously shown to exhibit potent anticoagulant and anticomplementary activities. In comparison to unsubstituted dextran which showed no significant (< 20%) adhesion inhibition at 1 mg/ml, dextrans increasingly substituted with carboxylic and benzylamide groups (CMBD) exhibited increasing anti-adhesive activities. Three CMBD derivatives showing an increasing proportion (5-14%) of benzylamide groups showed inhibition of bacterial adhesion increasing from 33 to 51% at 1 mg/ml. Another category of substituted dextrans having a variable proportion (2-26%) of sulfonated benzylamide groups (CMBDS) produced active inhibition of S. aureus adhesion. In comparison to these heparin-like dextran derivatives, native heparin produced inhibition values of S. aureus adhesion which were intermediate between those of CMBD and CMBDS compounds. Furthermore, the anti-adhesive activity was still expressed when substituted dextrans were preincubated with fibronectin-coated PMMA but washed away at the time when radiolabeled bacteria were added to the adhesion assay. This indicates that the anti-adhesive effects of CMBDS could be exerted at the level of the S. aureus binding site of fibronectin. In conclusion, S. aureus adhesion on fibronectin-coated biomaterials can be efficiently blocked in vitro by soluble compounds such as dextran derivatives."} {"id": "PMID:1283083", "title": "Structural abnormalities of the cricopharyngeus muscle in patients with pharyngeal (Zenker's) diverticulum.", "content": "Recent manometric and radiological studies suggest that the upper oesophageal sphincter has poor compliance in patients with a pharyngeal (Zenker's) diverticulum. To test the hypothesis that this phenomenon is related to structural changes within the cricopharyngeus muscle we examined, histologically, muscle strips from 14 patients with a Zenker's diverticulum and compared them with control tissue obtained at autopsy from 10 non-dysphagic individuals. The cricopharyngeus muscle from patients and controls differed from inferior constrictor muscle by virtue of type 1 fibre predominance and greater fibre size variability. Ragged red fibres and nemaline bodies are a normal finding in the cricopharyngeus. Marked differences were observed in the cricopharyngeus muscle of Zenker's patients which demonstrated fibro-adipose tissue replacement and fibre degeneration. It is concluded that these structural changes may account for the observed diminished upper oesophageal sphincter opening and dysphagia in patients with Zenker's diverticulum.", "contents": "Structural abnormalities of the cricopharyngeus muscle in patients with pharyngeal (Zenker's) diverticulum. Recent manometric and radiological studies suggest that the upper oesophageal sphincter has poor compliance in patients with a pharyngeal (Zenker's) diverticulum. To test the hypothesis that this phenomenon is related to structural changes within the cricopharyngeus muscle we examined, histologically, muscle strips from 14 patients with a Zenker's diverticulum and compared them with control tissue obtained at autopsy from 10 non-dysphagic individuals. The cricopharyngeus muscle from patients and controls differed from inferior constrictor muscle by virtue of type 1 fibre predominance and greater fibre size variability. Ragged red fibres and nemaline bodies are a normal finding in the cricopharyngeus. Marked differences were observed in the cricopharyngeus muscle of Zenker's patients which demonstrated fibro-adipose tissue replacement and fibre degeneration. It is concluded that these structural changes may account for the observed diminished upper oesophageal sphincter opening and dysphagia in patients with Zenker's diverticulum."} {"id": "PMID:1283087", "title": "Colony-stimulating factors in the clinic.", "content": "Recombinant purified human haemopoietic growth factors are available for clinical trials and some have been licensed for therapeutic use. Some haemopoietic lineages (erythroid, neutrophilic, monocyte-macrophagic) can be selectively stimulated in order to ameliorate the cytopenias that follow cytotoxic treatment, or that characterize some haematological syndromes, and to stimulate mature cell function. Advances in the knowledge of receptor-ligand interactions and of transduction mechanisms, plus the production of synthetic or mutant molecules that may mimic, potentiate or antagonize the effects of the natural growth factors, should make novel therapeutic approaches possible.", "contents": "Colony-stimulating factors in the clinic. Recombinant purified human haemopoietic growth factors are available for clinical trials and some have been licensed for therapeutic use. Some haemopoietic lineages (erythroid, neutrophilic, monocyte-macrophagic) can be selectively stimulated in order to ameliorate the cytopenias that follow cytotoxic treatment, or that characterize some haematological syndromes, and to stimulate mature cell function. Advances in the knowledge of receptor-ligand interactions and of transduction mechanisms, plus the production of synthetic or mutant molecules that may mimic, potentiate or antagonize the effects of the natural growth factors, should make novel therapeutic approaches possible."} {"id": "PMID:1283084", "title": "Clinical evaluation of a newly established anti-HCV assay for the diagnosis of hepatitis C in Japan.", "content": "To develop a more dependable method of diagnosing hepatitis C, serum anti-hepatitis C virus (HCV) was examined by using a new assay (anti-HCV second generation). The results were compared with those of either the conventional assay (anti-HCV first generation) or HCV-RNA analysis. With the first generation assay, anti-HCV was detected in 69% of post-transfusion acute hepatitis (AH), 44% of sporadic AH, 50% of needlestick exposed AH, 72% of chronic hepatitis (CH), 77% of liver cirrhosis (LC) and 86% of hepatocellular carcinoma (HCC). These results were remarkably increased by using the second generation assay (92% in post-transfusion AH, 72% in sporadic AH, 100% in needlestick exposed AH, 96% in CH, 96% in LC and 97% in HCC). Furthermore, in the early stages of AH (from 1-5 weeks after onset), anti-HCV was not detected in all 18 patients by the first generation assay, but was found in 10 of them by using the second generation assay. The failure to detect anti-HCV with the first generation assay was mainly due to a lack of the core region coding peptide (C22-3) in this assay. In the AH-resolving group, anti-HCV second generation did not disappear, but the titre tended to be lower than that in the CH-developing group. Thus, the second generation assay for anti-HCV was considered to be a more useful tool for not only the diagnosis of hepatitis C but also for determining prognosis.", "contents": "Clinical evaluation of a newly established anti-HCV assay for the diagnosis of hepatitis C in Japan. To develop a more dependable method of diagnosing hepatitis C, serum anti-hepatitis C virus (HCV) was examined by using a new assay (anti-HCV second generation). The results were compared with those of either the conventional assay (anti-HCV first generation) or HCV-RNA analysis. With the first generation assay, anti-HCV was detected in 69% of post-transfusion acute hepatitis (AH), 44% of sporadic AH, 50% of needlestick exposed AH, 72% of chronic hepatitis (CH), 77% of liver cirrhosis (LC) and 86% of hepatocellular carcinoma (HCC). These results were remarkably increased by using the second generation assay (92% in post-transfusion AH, 72% in sporadic AH, 100% in needlestick exposed AH, 96% in CH, 96% in LC and 97% in HCC). Furthermore, in the early stages of AH (from 1-5 weeks after onset), anti-HCV was not detected in all 18 patients by the first generation assay, but was found in 10 of them by using the second generation assay. The failure to detect anti-HCV with the first generation assay was mainly due to a lack of the core region coding peptide (C22-3) in this assay. In the AH-resolving group, anti-HCV second generation did not disappear, but the titre tended to be lower than that in the CH-developing group. Thus, the second generation assay for anti-HCV was considered to be a more useful tool for not only the diagnosis of hepatitis C but also for determining prognosis."} {"id": "PMID:1283088", "title": "[Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients].", "content": "From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, surgery was performed, otherwise radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial and in the first one: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. Complete response rate at the end of irradiation correlates with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule.", "contents": "[Role of neoadjuvant chemotherapy in the treatment of advanced head and neck tumors. Results of two randomized therapeutical trials conducted at the Institut Curie on 208 patients]. From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two trials randomizing induction chemotherapy versus no pre-irradiation treatment. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine, mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil (continuous infusion) and vindesine. Local treatment was the same in two trials: 'primary' radiotherapy in all patients. The response was then evaluated at 55 Gy; in the case of poor response, surgery was performed, otherwise radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial and in the first one: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. Complete response rate at the end of irradiation correlates with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval did not significantly differ in the two groups of patients, with or without chemotherapy. The incidence of distant metastasis was significantly reduced (P < 0.03) in the chemotherapy arms. This negative trial encourages the design of new chemotherapy protocols according to new schemes of treatment. For advanced stages of head and neck cancers (T3, T4, N2, N3), we recently launched a pilot study combining platinum and irradiation, but according to a concomitant schedule."} {"id": "PMID:1283085", "title": "Alpha-fetoprotein in patients with hepatocellular carcinoma after transcatheter arterial embolization.", "content": "To assess the usefulness of alpha-fetoprotein (AFP) in monitoring treatment effects of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients, a total of 31 sets of AFP levels after TAE in 21 HCC patients were analysed by linear regression between logarithmic AFP levels and days. Eleven sets of AFP data with poor linear declination were accompanied with poor TAE results except in one patient who had chronic hepatitis with acute exacerbations. Twenty sets of data with good linear declination in the first month after TAE indicated good TAE results. Seven of them showed no evidence of tumour recurrence nor elevated AFP levels within a follow-up of 6 months. The mean, standard deviation and range of half-lives of AFP in the non-recurrent group were 5.0, 1.6 and 2.9-7.2 days, respectively. The others experienced late tumour recurrence that was detected by rebound of AFP levels except one who had another non-AFP-secreting HCC. Thus, the results might be used as a reference in monitoring the treatment effects of TAE and the timing selection of repeated TAE.", "contents": "Alpha-fetoprotein in patients with hepatocellular carcinoma after transcatheter arterial embolization. To assess the usefulness of alpha-fetoprotein (AFP) in monitoring treatment effects of transcatheter arterial embolization (TAE) in hepatocellular carcinoma (HCC) patients, a total of 31 sets of AFP levels after TAE in 21 HCC patients were analysed by linear regression between logarithmic AFP levels and days. Eleven sets of AFP data with poor linear declination were accompanied with poor TAE results except in one patient who had chronic hepatitis with acute exacerbations. Twenty sets of data with good linear declination in the first month after TAE indicated good TAE results. Seven of them showed no evidence of tumour recurrence nor elevated AFP levels within a follow-up of 6 months. The mean, standard deviation and range of half-lives of AFP in the non-recurrent group were 5.0, 1.6 and 2.9-7.2 days, respectively. The others experienced late tumour recurrence that was detected by rebound of AFP levels except one who had another non-AFP-secreting HCC. Thus, the results might be used as a reference in monitoring the treatment effects of TAE and the timing selection of repeated TAE."} {"id": "PMID:1283089", "title": "Immunoblot analysis of the R-form lipopolysaccharide from Salmonella S forms.", "content": "Lipopolysaccharide (LPS) preparations from Salmonella S-form bacteria contain, in addition to S-form LPS, variable amounts of R-form material, lacking the O-specific polysaccharide. In the present study, we investigated the R-form LPS present in 22 LPS preparations derived from different Salmonella S-form strains belonging to 8 serological groups. The R-form part of the LPSs was separated by SDS-polyacrylamide gel electrophoresis and its antigen specificity analyzed by subsequent immunoblotting using Salmonella R-antisera (anti-Ra, -Rb1, -Rb2, -Rc). The results show that different R-determinants were present in one and the same LPS preparation. The pattern of reaction varied considerably among individual strains. This variation was also present among strains of the same serogroup. Approximately one half of the R-form LPSs exhibited a weak or no reaction with Ra antiserum. In contrast, almost all R-form LPSs showed a significant reaction with Rb1 antiserum. The electrophoretic mobility of the R-form material was very similar, exhibiting only minor differences among the different LPS preparations. In most cases, migration was similar to that of authentic Salmonella Ra-LPS; in some cases, the migration was somewhat faster resembling that of Rb1-LPS.", "contents": "Immunoblot analysis of the R-form lipopolysaccharide from Salmonella S forms. Lipopolysaccharide (LPS) preparations from Salmonella S-form bacteria contain, in addition to S-form LPS, variable amounts of R-form material, lacking the O-specific polysaccharide. In the present study, we investigated the R-form LPS present in 22 LPS preparations derived from different Salmonella S-form strains belonging to 8 serological groups. The R-form part of the LPSs was separated by SDS-polyacrylamide gel electrophoresis and its antigen specificity analyzed by subsequent immunoblotting using Salmonella R-antisera (anti-Ra, -Rb1, -Rb2, -Rc). The results show that different R-determinants were present in one and the same LPS preparation. The pattern of reaction varied considerably among individual strains. This variation was also present among strains of the same serogroup. Approximately one half of the R-form LPSs exhibited a weak or no reaction with Ra antiserum. In contrast, almost all R-form LPSs showed a significant reaction with Rb1 antiserum. The electrophoretic mobility of the R-form material was very similar, exhibiting only minor differences among the different LPS preparations. In most cases, migration was similar to that of authentic Salmonella Ra-LPS; in some cases, the migration was somewhat faster resembling that of Rb1-LPS."} {"id": "PMID:1283090", "title": "Species specific monoclonal antibodies to Bacteroides fragilis lipopolysaccharide protect mice from severe infection.", "content": "Four monoclonal antibodies which reacted in a species specific manner with Bacteroides fragilis were isolated. They recognised at least two different epitopes of B. fragilis lipopolysaccharide. The monoclonal antibodies protected non-immune mice from longlasting bacteraemia and abscess formation induced by the intraperitoneal administration of B. fragilis in combination with an infection-potentiating agent. The monoclonal antibodies were as efficient as an anti-B. fragilis hyperimmune serum. Only antibodies administered intraperitoneally or intramuscularly were protective.", "contents": "Species specific monoclonal antibodies to Bacteroides fragilis lipopolysaccharide protect mice from severe infection. Four monoclonal antibodies which reacted in a species specific manner with Bacteroides fragilis were isolated. They recognised at least two different epitopes of B. fragilis lipopolysaccharide. The monoclonal antibodies protected non-immune mice from longlasting bacteraemia and abscess formation induced by the intraperitoneal administration of B. fragilis in combination with an infection-potentiating agent. The monoclonal antibodies were as efficient as an anti-B. fragilis hyperimmune serum. Only antibodies administered intraperitoneally or intramuscularly were protective."} {"id": "PMID:1283091", "title": "Binding of Chlamydia trachomatis serovar L2 to collagen types I and IV, fibronectin, heparan sulphate, laminin and vitronectin.", "content": "Chlamydia trachomatis serovar L2 elementary bodies were tested for binding to 125I-labelled components of the extracellular matrix. C. trachomatis bound high levels of collagen type I and heparan sulphate, whereas the binding to collagen type IV, fibronectin, laminin and vitronectin was substantially less. Preliminary characterization showed that chlamydial surface proteins are essential for binding to occur. Our results suggest that a selective affinity for C. trachomatis to a limited number of components of the extracellular matrix may have important implications mediating attachment to host cell surfaces and localization of chlamydiae in other tissues, such as joints.", "contents": "Binding of Chlamydia trachomatis serovar L2 to collagen types I and IV, fibronectin, heparan sulphate, laminin and vitronectin. Chlamydia trachomatis serovar L2 elementary bodies were tested for binding to 125I-labelled components of the extracellular matrix. C. trachomatis bound high levels of collagen type I and heparan sulphate, whereas the binding to collagen type IV, fibronectin, laminin and vitronectin was substantially less. Preliminary characterization showed that chlamydial surface proteins are essential for binding to occur. Our results suggest that a selective affinity for C. trachomatis to a limited number of components of the extracellular matrix may have important implications mediating attachment to host cell surfaces and localization of chlamydiae in other tissues, such as joints."} {"id": "PMID:1283092", "title": "Monoclonal antibodies directed to the O antigen of Salmonella serogroup E cross-react with lipopolysaccharides of Salmonella serogroups C, F and S.", "content": "Four murine hybridoma clones secreting monoclonal antibodies (mAb) directed against lipopolysaccharide (LPS) antigen of S. newington, serogroup E1, were obtained after a fusion of spleen cells of mice immunized with formaldehyde-killed bacteria and mouse myeloma cells of the X63-Ag8.653 line. Antigen binding properties and specificity of the mAb were studied in bacterial agglutination tests, passive hemolysis and its inhibition, passive hemagglutination tests, passive hemolysis and its inhibition, passive hemagglutination and immunoenzyme tests (ELISA and immunoblotting). Three of the mAb (24E6, 29E1 and 45F6) were agglutinating and were active in all tests used, while mAb 31H12 did not agglutinate bacteria but revealed a high reactivity in the immunoenzyme reactions. It was found that the mAb reacted with LPS and Salmonella strains from serogroup E (E1, E2, E3 and E4) as well as from serogroups C (C1 and C4), F and S thus showing that the O3 antigen possesses more than one epitope, one of which is represented on the LPS antigens of the serovars from the cross-reacting groups mentioned. According to the known chemical the most probable recognized epitope consists of mannose with beta-linkage to the next monosaccharide residue in the LPS chain.", "contents": "Monoclonal antibodies directed to the O antigen of Salmonella serogroup E cross-react with lipopolysaccharides of Salmonella serogroups C, F and S. Four murine hybridoma clones secreting monoclonal antibodies (mAb) directed against lipopolysaccharide (LPS) antigen of S. newington, serogroup E1, were obtained after a fusion of spleen cells of mice immunized with formaldehyde-killed bacteria and mouse myeloma cells of the X63-Ag8.653 line. Antigen binding properties and specificity of the mAb were studied in bacterial agglutination tests, passive hemolysis and its inhibition, passive hemagglutination tests, passive hemolysis and its inhibition, passive hemagglutination and immunoenzyme tests (ELISA and immunoblotting). Three of the mAb (24E6, 29E1 and 45F6) were agglutinating and were active in all tests used, while mAb 31H12 did not agglutinate bacteria but revealed a high reactivity in the immunoenzyme reactions. It was found that the mAb reacted with LPS and Salmonella strains from serogroup E (E1, E2, E3 and E4) as well as from serogroups C (C1 and C4), F and S thus showing that the O3 antigen possesses more than one epitope, one of which is represented on the LPS antigens of the serovars from the cross-reacting groups mentioned. According to the known chemical the most probable recognized epitope consists of mannose with beta-linkage to the next monosaccharide residue in the LPS chain."} {"id": "PMID:1283093", "title": "Expression and purification of a soluble tissue factor fusion protein with an epitope for an unusual calcium-dependent antibody.", "content": "The use of bacterial signal peptides to target recombinant mammalian proteins to the periplasmic space of Escherichia coli (to promote proper disulfide bond formation) has met with variable success. We report the design and use of a bacterial expression vector to direct recombinant fusion proteins to the periplasmic space of E. coli: it contains the signal peptide from the pelB gene of Erwinia carotovora linked to a small peptide epitope for an unusual calcium-dependent antibody (HPC4). HPC4 binds to the epitope in a Ca(2+)-dependent manner, but the epitope itself does not bind Ca2+. We have used this system to express a biologically active, soluble form of tissue factor, the protein responsible for triggering the blood clotting cascade. Soluble tissue factor was secreted into the culture medium at 1-2 mg/liter, from which it could be readily purified using immobilized HPC4 antibody. The HPC4 epitope could be removed by digestion with thrombin or factor Xa, although a free amino terminus was not required for function since soluble tissue factor was equally active with the epitope still in place. This vector/epitope system permits large-scale expression and purification of recombinant soluble tissue factor and should be generally applicable to the isolation of other recombinant proteins. Furthermore, the epitope confers Ca(2+)-dependent binding of the fusion protein to HPC4 antibody while avoiding the creation of a new metal binding site on the fusion protein itself. Tb3+ can bind in this Ca2+ site near Trp, allowing this site to serve as a means of attaching a fluorescent probe to tissue factor.", "contents": "Expression and purification of a soluble tissue factor fusion protein with an epitope for an unusual calcium-dependent antibody. The use of bacterial signal peptides to target recombinant mammalian proteins to the periplasmic space of Escherichia coli (to promote proper disulfide bond formation) has met with variable success. We report the design and use of a bacterial expression vector to direct recombinant fusion proteins to the periplasmic space of E. coli: it contains the signal peptide from the pelB gene of Erwinia carotovora linked to a small peptide epitope for an unusual calcium-dependent antibody (HPC4). HPC4 binds to the epitope in a Ca(2+)-dependent manner, but the epitope itself does not bind Ca2+. We have used this system to express a biologically active, soluble form of tissue factor, the protein responsible for triggering the blood clotting cascade. Soluble tissue factor was secreted into the culture medium at 1-2 mg/liter, from which it could be readily purified using immobilized HPC4 antibody. The HPC4 epitope could be removed by digestion with thrombin or factor Xa, although a free amino terminus was not required for function since soluble tissue factor was equally active with the epitope still in place. This vector/epitope system permits large-scale expression and purification of recombinant soluble tissue factor and should be generally applicable to the isolation of other recombinant proteins. Furthermore, the epitope confers Ca(2+)-dependent binding of the fusion protein to HPC4 antibody while avoiding the creation of a new metal binding site on the fusion protein itself. Tb3+ can bind in this Ca2+ site near Trp, allowing this site to serve as a means of attaching a fluorescent probe to tissue factor."} {"id": "PMID:1283094", "title": "Phosphorylatable and epitope-tagged human erythropoietins: utility and purification of native baculovirus-derived forms.", "content": "The hematopoietic glycopeptide erythropoietin (EPO) is a prime regulator of red cell production in mammals, yet the precise nature of its interaction with specific cell surface receptors is poorly understood. Towards defining domains of EPO that are involved in receptor activation, we have developed (i) conditions for the expression of recombinant human EPO (rhEPO) at high levels in SF9 cells using modified 2- and 5-liter stirred reactors, (ii) a two-step procedure for the purification of this EPO without denaturation, and (iii) forms of EPO tagged with either a hemagglutinin influenza virus epitope or a consensus sequence for in vitro phosphorylation. Compared to EPO expressed in mammalian cells, rhEPO from SF9 cells in N-glycosylated with simple, neutral oligosaccharides of limited size, yet as purified presently using nondenaturing procedures, possesses exceptionally high in vitro activity (> or = 500,000 U/mg). Thus, this form of EPO should prove advantageous for direct physicochemical analyses. Regarding epitope-tagged and phosphorylatable EPOs, forms modified at the amino terminus (Ala1) fully retained receptor binding and in vitro biological activities. In contrast, forms modified at the carboxy terminus (Cys161) were inactive and did not compete for receptor binding, indicating that integrity of this domain is essential for receptor recognition. For active amino-terminal-modified forms, the specific binding of MAb 12CA5 to native HAI-EPO and the utility of 32P-labeled PHOS-EPO in receptor binding and internalization studies also were demonstrated. The development of these unique, highly active forms of human EPO should advance studies of essential interactions between this cytokine and its cell surface receptor.", "contents": "Phosphorylatable and epitope-tagged human erythropoietins: utility and purification of native baculovirus-derived forms. The hematopoietic glycopeptide erythropoietin (EPO) is a prime regulator of red cell production in mammals, yet the precise nature of its interaction with specific cell surface receptors is poorly understood. Towards defining domains of EPO that are involved in receptor activation, we have developed (i) conditions for the expression of recombinant human EPO (rhEPO) at high levels in SF9 cells using modified 2- and 5-liter stirred reactors, (ii) a two-step procedure for the purification of this EPO without denaturation, and (iii) forms of EPO tagged with either a hemagglutinin influenza virus epitope or a consensus sequence for in vitro phosphorylation. Compared to EPO expressed in mammalian cells, rhEPO from SF9 cells in N-glycosylated with simple, neutral oligosaccharides of limited size, yet as purified presently using nondenaturing procedures, possesses exceptionally high in vitro activity (> or = 500,000 U/mg). Thus, this form of EPO should prove advantageous for direct physicochemical analyses. Regarding epitope-tagged and phosphorylatable EPOs, forms modified at the amino terminus (Ala1) fully retained receptor binding and in vitro biological activities. In contrast, forms modified at the carboxy terminus (Cys161) were inactive and did not compete for receptor binding, indicating that integrity of this domain is essential for receptor recognition. For active amino-terminal-modified forms, the specific binding of MAb 12CA5 to native HAI-EPO and the utility of 32P-labeled PHOS-EPO in receptor binding and internalization studies also were demonstrated. The development of these unique, highly active forms of human EPO should advance studies of essential interactions between this cytokine and its cell surface receptor."} {"id": "PMID:1283095", "title": "Comparative purification of recombinant HIV-1 and HIV-2 reverse transcriptase: preparation of heterodimeric enzyme devoid of unprocessed gene product.", "content": "A procedure for producing and purifying recombinant HIV-1 and HIV-2 reverse transcriptase (RT) is described. These enzymes are produced by Escherichia coli-transformed with a plasmid containing the gene encoding for either the human immunodeficiency virus type 1 (HIV-1) or HIV-2 RT protein. Both proteins are partially processed by host cell proteases giving rise to a mixture of heterodimeric and nonheterodimeric products, which are subsequently resolved to near homogeneity by chromatography on phosphocellulose, Q-Sepharose, and hydrophobic interaction HPLC. Both HIV-1 (66/51 kDa) and HIV-2 (68/54 kDa) heterodimeric enzymes devoid of excess unprocessed (p66 or p68) precursors are isolated, enabling comparative enzymatic characterization of the fully active (and biologically relevant) heterodimeric forms. Homogenous HIV-1 and HIV-2 RT purified by this methodology exhibit near equivalent polymerase and RNase H activities.", "contents": "Comparative purification of recombinant HIV-1 and HIV-2 reverse transcriptase: preparation of heterodimeric enzyme devoid of unprocessed gene product. A procedure for producing and purifying recombinant HIV-1 and HIV-2 reverse transcriptase (RT) is described. These enzymes are produced by Escherichia coli-transformed with a plasmid containing the gene encoding for either the human immunodeficiency virus type 1 (HIV-1) or HIV-2 RT protein. Both proteins are partially processed by host cell proteases giving rise to a mixture of heterodimeric and nonheterodimeric products, which are subsequently resolved to near homogeneity by chromatography on phosphocellulose, Q-Sepharose, and hydrophobic interaction HPLC. Both HIV-1 (66/51 kDa) and HIV-2 (68/54 kDa) heterodimeric enzymes devoid of excess unprocessed (p66 or p68) precursors are isolated, enabling comparative enzymatic characterization of the fully active (and biologically relevant) heterodimeric forms. Homogenous HIV-1 and HIV-2 RT purified by this methodology exhibit near equivalent polymerase and RNase H activities."} {"id": "PMID:1283096", "title": "A rapid, two-step method for high-yield purification of recombinant rat acidic and basic fibroblast growth factors.", "content": "We describe the preparation of vectors for T7 polymerase-driven, high-level expression of rat acidic (aFGF) or basic (bFGF) fibroblast growth factors in Escherichia coli. Following isopropyl-beta-D-thiogalactoside induction of T7 polymerase, rat aFGF or bFGF represented a major portion of the proteins synthesized by vector-transformed E. coli. Passage of cell extracts through an Amicon YM-100 membrane provided ultrafiltrates containing either aFGF or bFGF as the principal component. A single heparin-Sepharose chromatography of the ultrafiltrates yielded essentially homogenous, biologically active, recombinant rat aFGF or bFGF. By silanizing vessels and using buffers containing 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid, we could store homogenous aFGF or bFGF preparations without significant loss during repeated freezing and thawing. Previous methods for purifying aFGF or bFGF utilized salt fractionation followed by sequential ion exchange and heparin-Sepharose chromatography. These purified aFGF or bFGF preparations routinely were stored in buffered carrier protein to minimize mitogen loss resulting from adsorption to glass or plastic surfaces. In contrast, the methods that we detail are rapid, require minimal manipulation of preparations, and permit storage of carrier-free, homogenous preparations without loss resulting from surface adsorption. The protocols can be used for preparation of homogenous aFGF or bFGF of other species and may be readily applied to the isolation and characterization of FGF-like mitogens present in cultured cell extracts, conditioned medium, or tissue preparations.", "contents": "A rapid, two-step method for high-yield purification of recombinant rat acidic and basic fibroblast growth factors. We describe the preparation of vectors for T7 polymerase-driven, high-level expression of rat acidic (aFGF) or basic (bFGF) fibroblast growth factors in Escherichia coli. Following isopropyl-beta-D-thiogalactoside induction of T7 polymerase, rat aFGF or bFGF represented a major portion of the proteins synthesized by vector-transformed E. coli. Passage of cell extracts through an Amicon YM-100 membrane provided ultrafiltrates containing either aFGF or bFGF as the principal component. A single heparin-Sepharose chromatography of the ultrafiltrates yielded essentially homogenous, biologically active, recombinant rat aFGF or bFGF. By silanizing vessels and using buffers containing 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonic acid, we could store homogenous aFGF or bFGF preparations without significant loss during repeated freezing and thawing. Previous methods for purifying aFGF or bFGF utilized salt fractionation followed by sequential ion exchange and heparin-Sepharose chromatography. These purified aFGF or bFGF preparations routinely were stored in buffered carrier protein to minimize mitogen loss resulting from adsorption to glass or plastic surfaces. In contrast, the methods that we detail are rapid, require minimal manipulation of preparations, and permit storage of carrier-free, homogenous preparations without loss resulting from surface adsorption. The protocols can be used for preparation of homogenous aFGF or bFGF of other species and may be readily applied to the isolation and characterization of FGF-like mitogens present in cultured cell extracts, conditioned medium, or tissue preparations."} {"id": "PMID:1283097", "title": "Induction of gene expression in muscle by the IGFs.", "content": "The insulin-like growth factors (IGFs) are usually studied with regard to their general effects on cell growth or differentiation, but the latter actions imply that IGFs may also have effects on expression of specific genes in differentiating target tissues. After 15 years of studies on IGF actions on muscle, we have (with the help of an outstanding group of collaborators) found three specific instances in which IGFs induce expression of a well-characterized gene with at least some degree of specificity. Each of the three genes under consideration plays a major role in the tissue that expresses it, and each of the three kinds of muscle is represented. The genes are (1) skeletal muscle myogenin, which plays a central role in terminal myogenic differentiation of muscle cells to form postmitotic myotubes, (2) smooth muscle aortic elastin, which is of major importance in regulation of blood pressure, and (3) cardiac beta-myosin heavy chain, which is the primary component of the contractile apparatus in older rodents and in all humans. For the first two of these, it has been established that the stimulation is largely if not completely at the level of increased mRNA synthesis, and that reporter gene constructs using 5-untranslated regions of the gene exhibit analogous responses to IGFs, offering the possibility that consensus IGF response elements can be elucidated. The importance of IGFs for skeletal myogenic differentiation is underscored by the observation that myoblasts in 'differentiation' medium exhibit substantial expression of IGF-II if IGFs are not added to the medium. Thus the IGFs play major roles in functions of all three kinds of muscle.+", "contents": "Induction of gene expression in muscle by the IGFs. The insulin-like growth factors (IGFs) are usually studied with regard to their general effects on cell growth or differentiation, but the latter actions imply that IGFs may also have effects on expression of specific genes in differentiating target tissues. After 15 years of studies on IGF actions on muscle, we have (with the help of an outstanding group of collaborators) found three specific instances in which IGFs induce expression of a well-characterized gene with at least some degree of specificity. Each of the three genes under consideration plays a major role in the tissue that expresses it, and each of the three kinds of muscle is represented. The genes are (1) skeletal muscle myogenin, which plays a central role in terminal myogenic differentiation of muscle cells to form postmitotic myotubes, (2) smooth muscle aortic elastin, which is of major importance in regulation of blood pressure, and (3) cardiac beta-myosin heavy chain, which is the primary component of the contractile apparatus in older rodents and in all humans. For the first two of these, it has been established that the stimulation is largely if not completely at the level of increased mRNA synthesis, and that reporter gene constructs using 5-untranslated regions of the gene exhibit analogous responses to IGFs, offering the possibility that consensus IGF response elements can be elucidated. The importance of IGFs for skeletal myogenic differentiation is underscored by the observation that myoblasts in 'differentiation' medium exhibit substantial expression of IGF-II if IGFs are not added to the medium. Thus the IGFs play major roles in functions of all three kinds of muscle.+"} {"id": "PMID:1283098", "title": "IGF-I and IGF binding proteins in diabetes-related kidney growth.", "content": "The kidney is a site of insulin-like growth factor I (IGF-I) production and IGF-I mediates effects on kidney growth and function. Diabetes is associated with kidney growth in man and the rat and, in the latter, commences within 48 h of induction of diabetes. Levels of kidney IGF-I are increased during the first 2-3 days of diabetes and this is at least partially due to increased production. Additionally, IGF-I binding is increased in diabetic rat kidney, due to increased binding to the IGF-I receptor and induction of proximal tubular binding protein expression. These changes are attenuated in prepubertal rats suggesting hormonal regulation. Further studies suggest that the changes are partly GH-dependent but independent of direct sex steroid effects. As kidney growth has been implicated in the subsequent development of diabetic nephropathy, further exploration of the close association between diabetes-related kidney growth and IGF-I accumulation may lead to an improved understanding of this complication.", "contents": "IGF-I and IGF binding proteins in diabetes-related kidney growth. The kidney is a site of insulin-like growth factor I (IGF-I) production and IGF-I mediates effects on kidney growth and function. Diabetes is associated with kidney growth in man and the rat and, in the latter, commences within 48 h of induction of diabetes. Levels of kidney IGF-I are increased during the first 2-3 days of diabetes and this is at least partially due to increased production. Additionally, IGF-I binding is increased in diabetic rat kidney, due to increased binding to the IGF-I receptor and induction of proximal tubular binding protein expression. These changes are attenuated in prepubertal rats suggesting hormonal regulation. Further studies suggest that the changes are partly GH-dependent but independent of direct sex steroid effects. As kidney growth has been implicated in the subsequent development of diabetic nephropathy, further exploration of the close association between diabetes-related kidney growth and IGF-I accumulation may lead to an improved understanding of this complication."} {"id": "PMID:1283100", "title": "Structural aspects of the IGFBP family.", "content": "To date six IGF binding proteins (IGFBP) have been characterized. Analysis of the amino acid sequence reveals that the IGFBPs are clearly distinct but are sharing regions with strong homology. Specifically the hydrophobic cysteine rich N-terminal region and to a lesser extend the C-terminal part are preserved. The alignment of the cysteine molecules is strongly conserved across the 6 IGFBPs. The middle one-third region, where no cysteines are present (except for IGFBP-4) is most divergent. IGFBP-3 and -4 are glycosylated, whereas IGFBP-1 and -2 contain an Arg-Gly-Asp sequence near the carboxyl terminus. Determination of the number of free-SH groups of IGFBP-1 and -3 has revealed that most likely all cysteine residues are involved in disulfide bond formation. All members of the IGFBP family bind IGF-I and IGF-II with about equal affinity. Studies involving deletion mutation and site-directed mutagenesis of IGFBP-1 and -3 have suggested that the three-dimensional structure of the protein plays an important role in IGF binding. However at present it is unclear whether the IGFBPs share one or more specific IGF binding domain. The predominant function of the IGFBPs is to allocate IGF in the various body fluid compartments and tissues and to modulate IGF binding to receptors. For this purpose there exists a very sophisticated control of the routing of circulating IGF both from and to the cell. There is mounting evidence that the structure of the IGFBP proteins plays a key role in the regulation of IGF bioavailability, by modulating its molecular size, capillary membrane permeability, target tissue specificity, cell membrane adherence and IGF affinity.", "contents": "Structural aspects of the IGFBP family. To date six IGF binding proteins (IGFBP) have been characterized. Analysis of the amino acid sequence reveals that the IGFBPs are clearly distinct but are sharing regions with strong homology. Specifically the hydrophobic cysteine rich N-terminal region and to a lesser extend the C-terminal part are preserved. The alignment of the cysteine molecules is strongly conserved across the 6 IGFBPs. The middle one-third region, where no cysteines are present (except for IGFBP-4) is most divergent. IGFBP-3 and -4 are glycosylated, whereas IGFBP-1 and -2 contain an Arg-Gly-Asp sequence near the carboxyl terminus. Determination of the number of free-SH groups of IGFBP-1 and -3 has revealed that most likely all cysteine residues are involved in disulfide bond formation. All members of the IGFBP family bind IGF-I and IGF-II with about equal affinity. Studies involving deletion mutation and site-directed mutagenesis of IGFBP-1 and -3 have suggested that the three-dimensional structure of the protein plays an important role in IGF binding. However at present it is unclear whether the IGFBPs share one or more specific IGF binding domain. The predominant function of the IGFBPs is to allocate IGF in the various body fluid compartments and tissues and to modulate IGF binding to receptors. For this purpose there exists a very sophisticated control of the routing of circulating IGF both from and to the cell. There is mounting evidence that the structure of the IGFBP proteins plays a key role in the regulation of IGF bioavailability, by modulating its molecular size, capillary membrane permeability, target tissue specificity, cell membrane adherence and IGF affinity."} {"id": "PMID:1283101", "title": "IGF binding proteins: regulation of cellular actions.", "content": "The recent purification and structural analysis of the six forms of insulin-like growth factor binding proteins has opened up the possibility of studying their mechanism of action at the cellular level. While a great deal of information has been published regarding control of secretion of these proteins by cells, their modulation of the target cell actions of the IGFs remains incompletely studied. Both IGFBP-1 and 3 have been shown to be bipotential regulators. Using one set of culture conditions, both proteins appear to inhibit IGF-mediated growth while if other conditions are used they appear to stimulate growth. IGFBP-2, 5 and 6 have been less well studied in this regard, although several studies showing growth inhibition with IGFBP-2 have been published. IGFBP-4 appears to be consistently inhibitory and no studies showing stimulation have been published to date. Recent research has focused on the reason for these bifunctional effects. Clearly the ability to adhere to cell surfaces appears to be one important property of these proteins that results in their ability to potentiate or inhibit growth. Likewise, phosphorylation of IGFBP-1 on serine residues appears to be a structurally modifying change which results in altered growth regulation. The future will no doubt uncover other post-translational modifications that result in modulation of biologic activity.", "contents": "IGF binding proteins: regulation of cellular actions. The recent purification and structural analysis of the six forms of insulin-like growth factor binding proteins has opened up the possibility of studying their mechanism of action at the cellular level. While a great deal of information has been published regarding control of secretion of these proteins by cells, their modulation of the target cell actions of the IGFs remains incompletely studied. Both IGFBP-1 and 3 have been shown to be bipotential regulators. Using one set of culture conditions, both proteins appear to inhibit IGF-mediated growth while if other conditions are used they appear to stimulate growth. IGFBP-2, 5 and 6 have been less well studied in this regard, although several studies showing growth inhibition with IGFBP-2 have been published. IGFBP-4 appears to be consistently inhibitory and no studies showing stimulation have been published to date. Recent research has focused on the reason for these bifunctional effects. Clearly the ability to adhere to cell surfaces appears to be one important property of these proteins that results in their ability to potentiate or inhibit growth. Likewise, phosphorylation of IGFBP-1 on serine residues appears to be a structurally modifying change which results in altered growth regulation. The future will no doubt uncover other post-translational modifications that result in modulation of biologic activity."} {"id": "PMID:1283104", "title": "Rectal obstruction secondary to carcinoma of the prostate treated by transanal resection of the prostate.", "content": "Rectal obstruction caused by carcinoma of the prostate is uncommon. If the disease does not respond to either hormonal treatment or radiotherapy, the only surgical means of relieving the obstruction has been the formation of a colostomy. We present an alternative treatment, since many of these patients are elderly with a short life expectancy and they may have difficulty coping with a stoma. Seven transanal endoscopic resections of the prostate (TARP) have been performed on 5 patients. The procedure is not without complications, but it does offer simple surgical palliation of the rectal obstruction and obviates the need for a colostomy.", "contents": "Rectal obstruction secondary to carcinoma of the prostate treated by transanal resection of the prostate. Rectal obstruction caused by carcinoma of the prostate is uncommon. If the disease does not respond to either hormonal treatment or radiotherapy, the only surgical means of relieving the obstruction has been the formation of a colostomy. We present an alternative treatment, since many of these patients are elderly with a short life expectancy and they may have difficulty coping with a stoma. Seven transanal endoscopic resections of the prostate (TARP) have been performed on 5 patients. The procedure is not without complications, but it does offer simple surgical palliation of the rectal obstruction and obviates the need for a colostomy."} {"id": "PMID:1283106", "title": "Oesophageal cancer: a population-based study of survival after treatment.", "content": "The survival of patients with oesophageal cancer diagnosed during the period 1982-1985 in Nottingham has been studied. Of 496 patients identified from endoscopy, histopathology and hospital activity analysis records, 268 (171 men) lived in the catchment area and had primary oesophageal cancer. Compared with previous studies the proportion of adenocarcinoma (35 per cent) was twice that expected, although survival was similar (hazard rate ratio at 2 years 1.0 (95 per cent confidence interval (c.i.) 0.8-1.4)) whether a squamous cell carcinoma or adenocarcinoma was present. Based on the original treatment intention, surgery was attempted in 34 per cent of cases and was associated with a median survival from diagnosis of 293 (95 per cent c.i. 232-367) days, with 41, 19 and 11 per cent surviving 1, 2 and 3 years respectively. Radical radiotherapy was attempted in 13 per cent of patients and was associated with a median survival of 190 (95 per cent c.i. 136-253) days, with 14, 6 and 6 per cent surviving 1, 2 and 3 years. Intubation alone was performed in 40 per cent of patients, of whom 44 per cent were aged over 75 years and 29 per cent had evidence of metastases, compared with 13 and 11 per cent respectively of those undergoing surgery or radical radiotherapy. The median survival for intubation alone was 100 (95 per cent c.i. 81-122) days, with 6, 3 and 0 per cent of patients surviving 1, 2 and 3 years respectively. Although patients treated surgically had the longest survival, these data indicate that overall survival after any active intervention is modest. Intubation alone is a reasonable option in those not suitable for surgery; randomized trials are needed to compare intubation with new methods of palliation.", "contents": "Oesophageal cancer: a population-based study of survival after treatment. The survival of patients with oesophageal cancer diagnosed during the period 1982-1985 in Nottingham has been studied. Of 496 patients identified from endoscopy, histopathology and hospital activity analysis records, 268 (171 men) lived in the catchment area and had primary oesophageal cancer. Compared with previous studies the proportion of adenocarcinoma (35 per cent) was twice that expected, although survival was similar (hazard rate ratio at 2 years 1.0 (95 per cent confidence interval (c.i.) 0.8-1.4)) whether a squamous cell carcinoma or adenocarcinoma was present. Based on the original treatment intention, surgery was attempted in 34 per cent of cases and was associated with a median survival from diagnosis of 293 (95 per cent c.i. 232-367) days, with 41, 19 and 11 per cent surviving 1, 2 and 3 years respectively. Radical radiotherapy was attempted in 13 per cent of patients and was associated with a median survival of 190 (95 per cent c.i. 136-253) days, with 14, 6 and 6 per cent surviving 1, 2 and 3 years. Intubation alone was performed in 40 per cent of patients, of whom 44 per cent were aged over 75 years and 29 per cent had evidence of metastases, compared with 13 and 11 per cent respectively of those undergoing surgery or radical radiotherapy. The median survival for intubation alone was 100 (95 per cent c.i. 81-122) days, with 6, 3 and 0 per cent of patients surviving 1, 2 and 3 years respectively. Although patients treated surgically had the longest survival, these data indicate that overall survival after any active intervention is modest. Intubation alone is a reasonable option in those not suitable for surgery; randomized trials are needed to compare intubation with new methods of palliation."} {"id": "PMID:1283109", "title": "The differential staining patterns of two lectins in the accessory olfactory bulb of the rat.", "content": "We examined the binding sites of Bandeiraea simplicifolia lectin I (BSL-I) and Vicia villosa agglutinin (VVA) which bind to the vomeronasal nerve of the rat. BSL-I stained the whole vomeronasal nerve and glomerular layers. VVA strongly stained the posterior 2/3, but weakly stained the anterior 1/3 of the glomerular layer. These results indicate that the glomeruli of the rat AOB have two subdivisions revealed by lectin histochemistry using BSL-I and VVA.", "contents": "The differential staining patterns of two lectins in the accessory olfactory bulb of the rat. We examined the binding sites of Bandeiraea simplicifolia lectin I (BSL-I) and Vicia villosa agglutinin (VVA) which bind to the vomeronasal nerve of the rat. BSL-I stained the whole vomeronasal nerve and glomerular layers. VVA strongly stained the posterior 2/3, but weakly stained the anterior 1/3 of the glomerular layer. These results indicate that the glomeruli of the rat AOB have two subdivisions revealed by lectin histochemistry using BSL-I and VVA."} {"id": "PMID:1283110", "title": "Dust from carpeted and smooth floors. V. Cat (Fel d I) and mite (Der p I and Der f I) allergen levels in school dust. Demonstration of the basophil histamine release induced by dust from classrooms.", "content": "Sixty dust samples from schools in Norway were analysed for major allergens from cat and mite after sampling with the regularly used vacuum cleaners for 5 days and with a new model vacuum cleaner for 10 days, respectively. The major feline allergen Felis domesticus allergen I (Fel d I) was detected in all the classrooms, with ranges from 12 to 16,840 ng/m2 floor area. The mean Fel d I concentration was about 11 times higher per unit area carpeted floors as compared with smooth floors after the 10 days sampling period. Mite allergens Dermatophagoides pteronyssinus allergen I (Der p I) and Dermatophagoides farinae allergen I (Der f I) were detected in very low concentrations, with ranges from < 1 ng to 104 ng/m2 floor area. These findings suggest that the school is a protective environment against mite infestation, while the prevalence of cat allergens in classrooms seems higher than previously assumed. Basophil histamine release was measured after provocation with 20 dust extracts from 10 different schools. In nine of the 10 schools examined, the basophil histamine release caused by challenge with carpet dust was higher than the corresponding release with smooth floor dust. The calculated floor areas in each school in which dust led to 15% histamine release were from 2 to 55 times larger for smooth floors compared with carpeted floors. These results emphasize previous findings regarding higher allergen concentrations in classrooms with carpeted floors.", "contents": "Dust from carpeted and smooth floors. V. Cat (Fel d I) and mite (Der p I and Der f I) allergen levels in school dust. Demonstration of the basophil histamine release induced by dust from classrooms. Sixty dust samples from schools in Norway were analysed for major allergens from cat and mite after sampling with the regularly used vacuum cleaners for 5 days and with a new model vacuum cleaner for 10 days, respectively. The major feline allergen Felis domesticus allergen I (Fel d I) was detected in all the classrooms, with ranges from 12 to 16,840 ng/m2 floor area. The mean Fel d I concentration was about 11 times higher per unit area carpeted floors as compared with smooth floors after the 10 days sampling period. Mite allergens Dermatophagoides pteronyssinus allergen I (Der p I) and Dermatophagoides farinae allergen I (Der f I) were detected in very low concentrations, with ranges from < 1 ng to 104 ng/m2 floor area. These findings suggest that the school is a protective environment against mite infestation, while the prevalence of cat allergens in classrooms seems higher than previously assumed. Basophil histamine release was measured after provocation with 20 dust extracts from 10 different schools. In nine of the 10 schools examined, the basophil histamine release caused by challenge with carpet dust was higher than the corresponding release with smooth floor dust. The calculated floor areas in each school in which dust led to 15% histamine release were from 2 to 55 times larger for smooth floors compared with carpeted floors. These results emphasize previous findings regarding higher allergen concentrations in classrooms with carpeted floors."} {"id": "PMID:1283111", "title": "'Hemorrhagic' and microvascular phenomena within the arterial wall.", "content": "To study microvasculature and hemorrhage within the arterial wall. Human autopsy specimens of the arch of the aorta, the carotid, brachiocephalic, subclavian and coronary arteries perfused with liquid casting material and maintained at physiological pressure until the material had set. Evidence of dense microvasculature and other phenomena which have the morphological appearance of 'hemorrhage' within the arterial wall, coupled with calcified matter and other impressions made on the cast by atherosclerotic plaques. The findings lend support to suggestions in the literature that neovascularization may play a role in the pathogenesis of coronary atherosclerosis and its sequelae, that hemorrhage into the intima may be due to rupture of capillaries which are derived from the coronary lumen, and that an increase in microvasculature occurs in the immediate vicinity of localized atherosclerotic lesions.", "contents": "'Hemorrhagic' and microvascular phenomena within the arterial wall. To study microvasculature and hemorrhage within the arterial wall. Human autopsy specimens of the arch of the aorta, the carotid, brachiocephalic, subclavian and coronary arteries perfused with liquid casting material and maintained at physiological pressure until the material had set. Evidence of dense microvasculature and other phenomena which have the morphological appearance of 'hemorrhage' within the arterial wall, coupled with calcified matter and other impressions made on the cast by atherosclerotic plaques. The findings lend support to suggestions in the literature that neovascularization may play a role in the pathogenesis of coronary atherosclerosis and its sequelae, that hemorrhage into the intima may be due to rupture of capillaries which are derived from the coronary lumen, and that an increase in microvasculature occurs in the immediate vicinity of localized atherosclerotic lesions."} {"id": "PMID:1283112", "title": "Chromosomal sensitivity of human lymphocytes to bleomycin. Influence of antioxidant enzyme activities in whole blood and different blood fractions.", "content": "The activity of the antioxidant enzymes catalase (CAT), peroxidases (POD), and superoxide dismutases (SOD) in whole blood and different blood fractions was analyzed in 20 normal human beings and correlated with the chromosomal sensitivity of lymphocytes to bleomycin (BLM) (measured as frequency of dicentric chromosomes per BLM dose). Our results demonstrate that both the physiologic activities of the enzymes and the chromosomal sensitivity to BLM exhibit an ample and significant interindividual variability. An inverse and linear correlation between chromosomal sensitivity to BLM and the concentration of 1) CAT and POD in plasma and 2) SOD in whole blood, erythrocytes, and plasma was found. On the other hand, the chromosomal sensitivity to BLM showed a direct correlation with the concentration of SOD and POD in mononuclear leukocytes. It is suggested that a determination of antioxidant enzyme (AOE) activities in a given cell population may serve to predict the chromosomal sensitivity to BLM.", "contents": "Chromosomal sensitivity of human lymphocytes to bleomycin. Influence of antioxidant enzyme activities in whole blood and different blood fractions. The activity of the antioxidant enzymes catalase (CAT), peroxidases (POD), and superoxide dismutases (SOD) in whole blood and different blood fractions was analyzed in 20 normal human beings and correlated with the chromosomal sensitivity of lymphocytes to bleomycin (BLM) (measured as frequency of dicentric chromosomes per BLM dose). Our results demonstrate that both the physiologic activities of the enzymes and the chromosomal sensitivity to BLM exhibit an ample and significant interindividual variability. An inverse and linear correlation between chromosomal sensitivity to BLM and the concentration of 1) CAT and POD in plasma and 2) SOD in whole blood, erythrocytes, and plasma was found. On the other hand, the chromosomal sensitivity to BLM showed a direct correlation with the concentration of SOD and POD in mononuclear leukocytes. It is suggested that a determination of antioxidant enzyme (AOE) activities in a given cell population may serve to predict the chromosomal sensitivity to BLM."} {"id": "PMID:1283113", "title": "Pericyte involvement in capillary sprouting during angiogenesis in situ.", "content": "To investigate the participation of microvascular pericytes in the process of capillary sprouting, we examined whole-mount preparations of the rat mesentery by use of a double immunofluorescence approach. Angiogenesis was induced by intraperitoneal injections of either the mast cell-degranulating substance compound 48/80 or tumor cell-conditioned medium. Capillary sprouts were visualized by staining with rhodamine-conjugated phalloidin and pericytes were simultaneously stained by an antibody to the intermediate filament protein desmin. Developing pericytes were negative for the smooth-muscle isoform of alpha-actin, but were clearly reactive for desmin. Pericytes appear to be involved in the earliest stages of capillary sprouting. Pericytes were regularly found lying at and in front of the advancing tips of endothelial sprouts. At many sites pericytes were seen to bridge the gap between the leading edges of opposing endothelial sprouts, which were apparently preparing to merge, suggesting that pericytic processes may serve as guiding structures aiding outgrowth of endothelial cells.", "contents": "Pericyte involvement in capillary sprouting during angiogenesis in situ. To investigate the participation of microvascular pericytes in the process of capillary sprouting, we examined whole-mount preparations of the rat mesentery by use of a double immunofluorescence approach. Angiogenesis was induced by intraperitoneal injections of either the mast cell-degranulating substance compound 48/80 or tumor cell-conditioned medium. Capillary sprouts were visualized by staining with rhodamine-conjugated phalloidin and pericytes were simultaneously stained by an antibody to the intermediate filament protein desmin. Developing pericytes were negative for the smooth-muscle isoform of alpha-actin, but were clearly reactive for desmin. Pericytes appear to be involved in the earliest stages of capillary sprouting. Pericytes were regularly found lying at and in front of the advancing tips of endothelial sprouts. At many sites pericytes were seen to bridge the gap between the leading edges of opposing endothelial sprouts, which were apparently preparing to merge, suggesting that pericytic processes may serve as guiding structures aiding outgrowth of endothelial cells."} {"id": "PMID:1283114", "title": "[Dynamics of vascular changes in neovascular glaucoma. I. Development of rubeosis iridis after cryosurgery].", "content": "The author is evaluating the influence of two cryosurgical methods for the development of the rubeosis of iris in neovascular glaucoma. The cyclocryocoagulation was used as a single method in 12 eyes, the combination of transscleral panretinal cryocoagulation and cyclocryocoagulation in 26 eyes. The results were clearly better if the combination of cryosurgical methods was used. The involution of rubeosis of iris was observed in 6 weeks in all patients after the transscleral panretinal photocoagulation in combination with cyclocryocoagulation. The author thinks that the non-satisfactory regression of the rubeosis in neovascular glaucoma after simple cyclocryocoagulation is caused by the fact, that by this method we affect just one factor in the pathogenesis of rubeosis. The author is suggesting that there are two factors influencing the pathogenesis of the rubeosis of iris: the primary disease, that is causing the development of proliferative retinopathy; and the high intraocular pressure, that is reducing the blood flow in retinal vessels and by this is increasing the hypoxia of the retina.", "contents": "[Dynamics of vascular changes in neovascular glaucoma. I. Development of rubeosis iridis after cryosurgery]. The author is evaluating the influence of two cryosurgical methods for the development of the rubeosis of iris in neovascular glaucoma. The cyclocryocoagulation was used as a single method in 12 eyes, the combination of transscleral panretinal cryocoagulation and cyclocryocoagulation in 26 eyes. The results were clearly better if the combination of cryosurgical methods was used. The involution of rubeosis of iris was observed in 6 weeks in all patients after the transscleral panretinal photocoagulation in combination with cyclocryocoagulation. The author thinks that the non-satisfactory regression of the rubeosis in neovascular glaucoma after simple cyclocryocoagulation is caused by the fact, that by this method we affect just one factor in the pathogenesis of rubeosis. The author is suggesting that there are two factors influencing the pathogenesis of the rubeosis of iris: the primary disease, that is causing the development of proliferative retinopathy; and the high intraocular pressure, that is reducing the blood flow in retinal vessels and by this is increasing the hypoxia of the retina."} {"id": "PMID:1283115", "title": "[Dynamics of vascular changes in neovascular glaucoma. II. Unusual findings after cryosurgery].", "content": "New, yet published findings after the combination of transscleral panretinal cryocoagulation and cyclocryocoagulation are presented. The author describes the difference in regression of small and large neovascularisations of the iris after the cryosurgery; the difference in blood flow in these vessels is shown angiographically. The discordance in the biomicroscopical findings of neovascularisations of the iris and angiographical picture in connection with high intraocular pressure in neovascular glaucoma is shown. The iridoplegia was found only in patients after the transscleral panretinal cryocoagulation, not in patients after simple cyclocryocoagulation. The mortality rate in neovascular glaucoma is 55% in 3 years, but mostly in 2 years.", "contents": "[Dynamics of vascular changes in neovascular glaucoma. II. Unusual findings after cryosurgery]. New, yet published findings after the combination of transscleral panretinal cryocoagulation and cyclocryocoagulation are presented. The author describes the difference in regression of small and large neovascularisations of the iris after the cryosurgery; the difference in blood flow in these vessels is shown angiographically. The discordance in the biomicroscopical findings of neovascularisations of the iris and angiographical picture in connection with high intraocular pressure in neovascular glaucoma is shown. The iridoplegia was found only in patients after the transscleral panretinal cryocoagulation, not in patients after simple cyclocryocoagulation. The mortality rate in neovascular glaucoma is 55% in 3 years, but mostly in 2 years."} {"id": "PMID:1283117", "title": "Prolonged treatment with finasteride (a 5 alpha-reductase inhibitor) does not affect bone density and metabolism.", "content": "Since it is not clear whether testosterone or dihydrotestosterone is the active hormone in bone metabolism, we wished to assess the effect of finasteride, a 5 alpha-reductase inhibitor, or vertebral bone mineral density and parameters of bone and mineral metabolism. Patients were treated in a randomized, double-blind controlled study with either placebo, 1 or 5 mg/day finasteride. Twenty-three men with benign prostatic hyperplasia (BPH) were included in this study; eight received placebo, seven were allocated to treatment with 1 mg/day, and eight to 5 mg/day finasteride for 12 months. Vertebral bone mineral density was measured at the lumbar spine by dual energy X-ray bone densitometry. Serum calcium, phosphorus, parathyroid hormone, osteocalcin and vitamin D metabolites were measured regularly. Urinary calcium and creatinine excretion were monitored as well. Finasteride caused a significant decrease in serum dihydrotestosterone after 6 and 12 months, but no effect on serum testosterone. Vertebral bone mineral density remained unaltered. None of the other parameters monitored were affected except for a small unexplained increase in 1.25-dihydroxyvitamin D in the group receiving 5 mg finasteride/day. Testosterone is probably the active hormone in bone metabolism. However, oestradiol, the product of testosterone aromatization (which remains unaltered under finasteride) may yet be another possible responsible steroid in the maintenance of bone density. We can also not rule out that the small amount of dihydrotestosterone remaining under finasteride administration is sufficient for maintaining normal bone metabolism.", "contents": "Prolonged treatment with finasteride (a 5 alpha-reductase inhibitor) does not affect bone density and metabolism. Since it is not clear whether testosterone or dihydrotestosterone is the active hormone in bone metabolism, we wished to assess the effect of finasteride, a 5 alpha-reductase inhibitor, or vertebral bone mineral density and parameters of bone and mineral metabolism. Patients were treated in a randomized, double-blind controlled study with either placebo, 1 or 5 mg/day finasteride. Twenty-three men with benign prostatic hyperplasia (BPH) were included in this study; eight received placebo, seven were allocated to treatment with 1 mg/day, and eight to 5 mg/day finasteride for 12 months. Vertebral bone mineral density was measured at the lumbar spine by dual energy X-ray bone densitometry. Serum calcium, phosphorus, parathyroid hormone, osteocalcin and vitamin D metabolites were measured regularly. Urinary calcium and creatinine excretion were monitored as well. Finasteride caused a significant decrease in serum dihydrotestosterone after 6 and 12 months, but no effect on serum testosterone. Vertebral bone mineral density remained unaltered. None of the other parameters monitored were affected except for a small unexplained increase in 1.25-dihydroxyvitamin D in the group receiving 5 mg finasteride/day. Testosterone is probably the active hormone in bone metabolism. However, oestradiol, the product of testosterone aromatization (which remains unaltered under finasteride) may yet be another possible responsible steroid in the maintenance of bone density. We can also not rule out that the small amount of dihydrotestosterone remaining under finasteride administration is sufficient for maintaining normal bone metabolism."} {"id": "PMID:1283118", "title": "Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma.", "content": "We describe a case of Cushing's syndrome caused by a phaeochromocytoma secreting corticotrophin-releasing hormone (CRH) and corticotrophin (ACTH). A 49-year-old white woman presented with a 1-month history of lower limb oedema, polydipsia and polyuria. Physical examination revealed a patient with plethoric facies, lanugo-type facial hair, central obesity, red abdominal striae, lower limb oedema, and blood pressure of 210/115 mmHg. Laboratory studies showed high plasma ACTH and markedly elevated urinary cortisol excretion that suppressed more than 50% with high-dose dexamethasone administration. Computed tomographic scan of the abdomen showed a 4-cm left adrenal tumour. Catecholamines and metabolites were markedly increased in a 24-hour urine collection. Results of venous catheterization studies showed that CRH and ACTH were secreted by the tumour. In addition, with ovine CRH administration, inferior petrosal sinus sampling showed pituitary secretion of ACTH. Left adrenalectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohistochemical studies revealed a phaeochromocytoma that produced CRH, ACTH and vasopressin. RNA studies showed that this tumour, in contrast to normal adrenal and other reported phaeochromocytomas, transcribed a lone pituitary-sized (1200 nucleotide) pro-opiomelanocortin mRNA. This is the second reported case of a CRH-secreting phaeochromocytoma.", "contents": "Cushing's syndrome associated with ectopic production of corticotrophin-releasing hormone, corticotrophin and vasopressin by a phaeochromocytoma. We describe a case of Cushing's syndrome caused by a phaeochromocytoma secreting corticotrophin-releasing hormone (CRH) and corticotrophin (ACTH). A 49-year-old white woman presented with a 1-month history of lower limb oedema, polydipsia and polyuria. Physical examination revealed a patient with plethoric facies, lanugo-type facial hair, central obesity, red abdominal striae, lower limb oedema, and blood pressure of 210/115 mmHg. Laboratory studies showed high plasma ACTH and markedly elevated urinary cortisol excretion that suppressed more than 50% with high-dose dexamethasone administration. Computed tomographic scan of the abdomen showed a 4-cm left adrenal tumour. Catecholamines and metabolites were markedly increased in a 24-hour urine collection. Results of venous catheterization studies showed that CRH and ACTH were secreted by the tumour. In addition, with ovine CRH administration, inferior petrosal sinus sampling showed pituitary secretion of ACTH. Left adrenalectomy resulted in complete remission of Cushing's syndrome. Light microscopic and immunohistochemical studies revealed a phaeochromocytoma that produced CRH, ACTH and vasopressin. RNA studies showed that this tumour, in contrast to normal adrenal and other reported phaeochromocytomas, transcribed a lone pituitary-sized (1200 nucleotide) pro-opiomelanocortin mRNA. This is the second reported case of a CRH-secreting phaeochromocytoma."} {"id": "PMID:1283119", "title": "Deciphering the fluorescent variability of human genomic heterochromatin by DA/DAPI technique.", "content": "A number of selective staining techniques have been utilized to decipher the variability of pericentromeric heterochromatin. One such technique is called DA/DAPI and it is believed to be stain specific. However, we demonstrate otherwise and suggest that pericentromeric regions of all human chromosomes stain positive by DA/DAPI-technique. It must be emphasized that the incidence of DA/DAPI positive stained chromosomes, other than 1, 9, 15, 16 and Y, is a rare occurrence and only a small portion of the pericentromeric region is DA/DAPI positive, as reported here using 50 normal individuals.", "contents": "Deciphering the fluorescent variability of human genomic heterochromatin by DA/DAPI technique. A number of selective staining techniques have been utilized to decipher the variability of pericentromeric heterochromatin. One such technique is called DA/DAPI and it is believed to be stain specific. However, we demonstrate otherwise and suggest that pericentromeric regions of all human chromosomes stain positive by DA/DAPI-technique. It must be emphasized that the incidence of DA/DAPI positive stained chromosomes, other than 1, 9, 15, 16 and Y, is a rare occurrence and only a small portion of the pericentromeric region is DA/DAPI positive, as reported here using 50 normal individuals."} {"id": "PMID:1283120", "title": "Granzyme A-immunoreactive cells in synovial fluid in reactive and rheumatoid arthritis.", "content": "Perforin and granzyme A co-localize in the cytotoxic granules of killer cells like cytotoxic T lymphocytes (CTL). Perforin is the cytolytic pore-forming protein, whereas the function of the homodimeric serine protease granzyme A and other members of the granzyme family is still unclear. Granzyme A-immunoreactive cells formed 8 +/- 2% of the resting peripheral blood lymphocytes of healthy individuals. In contrast, granzyme A-positive cells formed 15% of peripheral blood mononuclear cells in patients with reactive or rheumatoid arthritis. However, 29 +/- 4% (p < 0.05 compared to normal peripheral blood) and 25 +/- 4% (p < 0.05) of all lymphocytes in synovial fluid in reactive and rheumatoid arthritis, respectively, were granzyme A-positive. This suggests involvement of cell-mediated cytolytic mechanisms in the articular pathogenic mechanisms. This involvement, however, does not differentiate between reactive and rheumatoid arthritis.", "contents": "Granzyme A-immunoreactive cells in synovial fluid in reactive and rheumatoid arthritis. Perforin and granzyme A co-localize in the cytotoxic granules of killer cells like cytotoxic T lymphocytes (CTL). Perforin is the cytolytic pore-forming protein, whereas the function of the homodimeric serine protease granzyme A and other members of the granzyme family is still unclear. Granzyme A-immunoreactive cells formed 8 +/- 2% of the resting peripheral blood lymphocytes of healthy individuals. In contrast, granzyme A-positive cells formed 15% of peripheral blood mononuclear cells in patients with reactive or rheumatoid arthritis. However, 29 +/- 4% (p < 0.05 compared to normal peripheral blood) and 25 +/- 4% (p < 0.05) of all lymphocytes in synovial fluid in reactive and rheumatoid arthritis, respectively, were granzyme A-positive. This suggests involvement of cell-mediated cytolytic mechanisms in the articular pathogenic mechanisms. This involvement, however, does not differentiate between reactive and rheumatoid arthritis."} {"id": "PMID:1283121", "title": "Complex carbohydrate presence in the gut and Malpighian tubules of Drosophila auraria larvae (Insecta, Diptera): a cytochemical study.", "content": "Cytochemical techniques were used for the qualitative characterization of carbohydrates in the foregut, midgut, hindgut and Malpighian tubules of Drosophila auraria larvae. Periodate-reactive (neutral) polysaccharides were present in the foregut cuticle, peritrophic membrane, cells of the proventriculus which produce the peritrophic membrane, as well as the glycocalyx of the midgut and Malpighian tubule cells. Sulphated and carboxylated complex carbohydrates were detected in the cuticle of both foregut and hindgut, as well as the 'vacuoles with granules' in the Malpighian tubules. Periodate-reactive sulphated and carboxylated polysaccharides were detected in dense bodies appearing in all cells 10-20 h before pupation of larvae. The significance of the presence or absence of complex carbohydrates in D. auraria larval digestive system is discussed and compared with results found in the digestive system of other insects. In addition, the efficiency of the HID-TCH-SP and LID-TCH-SP techniques in staining lysosomes is discussed.", "contents": "Complex carbohydrate presence in the gut and Malpighian tubules of Drosophila auraria larvae (Insecta, Diptera): a cytochemical study. Cytochemical techniques were used for the qualitative characterization of carbohydrates in the foregut, midgut, hindgut and Malpighian tubules of Drosophila auraria larvae. Periodate-reactive (neutral) polysaccharides were present in the foregut cuticle, peritrophic membrane, cells of the proventriculus which produce the peritrophic membrane, as well as the glycocalyx of the midgut and Malpighian tubule cells. Sulphated and carboxylated complex carbohydrates were detected in the cuticle of both foregut and hindgut, as well as the 'vacuoles with granules' in the Malpighian tubules. Periodate-reactive sulphated and carboxylated polysaccharides were detected in dense bodies appearing in all cells 10-20 h before pupation of larvae. The significance of the presence or absence of complex carbohydrates in D. auraria larval digestive system is discussed and compared with results found in the digestive system of other insects. In addition, the efficiency of the HID-TCH-SP and LID-TCH-SP techniques in staining lysosomes is discussed."} {"id": "PMID:1283122", "title": "Regulation of Staphylococcus protease using complement, interferon and immunoglobulin as substrates.", "content": "The effects of various agents on the cleavage of serum albumin, interferon, immunoglobulin and complement component C1q by the extracellular protease from Staphylococcus aureus were analysed by SDS-polyacrylamide gel electrophoresis. Arachidonic acid moderately stimulated the proteolysis of serum albumin, interferon and complement component. Phosphatidic acid effectively enhanced the proteolysis of serum albumin and IgG, whereas it inhibited the cleavage of IgM. The proteolysis of IgG was appreciably enhanced by sphingosine. In contrast, phosphatidyl choline and phosphatidyl glycerol were shown to have an inhibitory effect on the proteolysis of IgG and IgM. Phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine also inhibited the proteolysis of IgG. The failure of any of these agents to exert a persistent effect on the cleavage of all substrates, revealed the complexity of the interactions among the agent, the substrate and the protease.", "contents": "Regulation of Staphylococcus protease using complement, interferon and immunoglobulin as substrates. The effects of various agents on the cleavage of serum albumin, interferon, immunoglobulin and complement component C1q by the extracellular protease from Staphylococcus aureus were analysed by SDS-polyacrylamide gel electrophoresis. Arachidonic acid moderately stimulated the proteolysis of serum albumin, interferon and complement component. Phosphatidic acid effectively enhanced the proteolysis of serum albumin and IgG, whereas it inhibited the cleavage of IgM. The proteolysis of IgG was appreciably enhanced by sphingosine. In contrast, phosphatidyl choline and phosphatidyl glycerol were shown to have an inhibitory effect on the proteolysis of IgG and IgM. Phosphatidyl serine, phosphatidyl inositol and phosphatidyl ethanolamine also inhibited the proteolysis of IgG. The failure of any of these agents to exert a persistent effect on the cleavage of all substrates, revealed the complexity of the interactions among the agent, the substrate and the protease."} {"id": "PMID:1283123", "title": "Aberrant Myc expression in the murine trisomy 15 syndrome is correlated with prolonged proliferation in spongiotrophoblast cells of the placenta.", "content": "In the mouse the protooncogene Myc is localized to Chromosome 15. Embryos with trisomy 15 (Ts15) are severely retarded and die in utero at an early stage. The placenta of these embryos shows enlargement of the fetal spongiotrophoblast. In the spongiotrophoblast and giant cells of the normal euploid placenta, Myc expression declines from day 10.5 of gestation onward whereas Myc expression persists at a high level in Ts15 cells. At the same time these Ts15 cells show prolonged proliferation which consequently leads to the observed enlargement of that tissue layer in Ts15 placentas.", "contents": "Aberrant Myc expression in the murine trisomy 15 syndrome is correlated with prolonged proliferation in spongiotrophoblast cells of the placenta. In the mouse the protooncogene Myc is localized to Chromosome 15. Embryos with trisomy 15 (Ts15) are severely retarded and die in utero at an early stage. The placenta of these embryos shows enlargement of the fetal spongiotrophoblast. In the spongiotrophoblast and giant cells of the normal euploid placenta, Myc expression declines from day 10.5 of gestation onward whereas Myc expression persists at a high level in Ts15 cells. At the same time these Ts15 cells show prolonged proliferation which consequently leads to the observed enlargement of that tissue layer in Ts15 placentas."} {"id": "PMID:1283124", "title": "The thymus: new views of an old gland.", "content": "The existence of the thymus was recognised by ancient scientists and doctors, although its vital role in the development and maintenance of the competent T cell repertoire has been fully appreciated only comparatively recently. Current research is now moving on to explore the role of the thymus in interactions between the brain, the nervous system and the immune response. This is an exciting new field which should lead to advances in the management, treatment and prognosis of disease in man and animals.", "contents": "The thymus: new views of an old gland. The existence of the thymus was recognised by ancient scientists and doctors, although its vital role in the development and maintenance of the competent T cell repertoire has been fully appreciated only comparatively recently. Current research is now moving on to explore the role of the thymus in interactions between the brain, the nervous system and the immune response. This is an exciting new field which should lead to advances in the management, treatment and prognosis of disease in man and animals."} {"id": "PMID:1283125", "title": "The organisation of production of genetically-engineered proteins in yeast.", "content": "The use of a variety of genetic-engineering techniques to introduce foreign DNA into living yeast cells has resulted in the production in these cells of the corresponding proteins. These include enzymes, antibodies, vaccines, anti-viral agents, and hormones. This article discusses the techniques of genetic engineering in yeast and suggests the lines of future progress in the economic production of novel proteins for use in therapy.", "contents": "The organisation of production of genetically-engineered proteins in yeast. The use of a variety of genetic-engineering techniques to introduce foreign DNA into living yeast cells has resulted in the production in these cells of the corresponding proteins. These include enzymes, antibodies, vaccines, anti-viral agents, and hormones. This article discusses the techniques of genetic engineering in yeast and suggests the lines of future progress in the economic production of novel proteins for use in therapy."} {"id": "PMID:1283126", "title": "Serodiagnostic value of the 19 kilodalton antigen of Mycobacterium tuberculosis in Indian patients.", "content": "Previous studies in UK subjects suggested that the 19 kDa protein antigen of Mycobacterium tuberculosis might be valuable in the serodiagnosis of paucibacillary tuberculosis. In this study, antibody titres for the 19 kDa antigen were higher in healthy controls in India than in the UK. Consequently, the diagnostic sensitivity of this antigen and its TB23 epitope was negligible in Indian patients with tuberculosis. However, a diagnostic sensitivity of 50% was achieved in patients with skin tuberculosis on the basis of a high ratio between antibody titres for the whole antigen and its TB23 epitope.", "contents": "Serodiagnostic value of the 19 kilodalton antigen of Mycobacterium tuberculosis in Indian patients. Previous studies in UK subjects suggested that the 19 kDa protein antigen of Mycobacterium tuberculosis might be valuable in the serodiagnosis of paucibacillary tuberculosis. In this study, antibody titres for the 19 kDa antigen were higher in healthy controls in India than in the UK. Consequently, the diagnostic sensitivity of this antigen and its TB23 epitope was negligible in Indian patients with tuberculosis. However, a diagnostic sensitivity of 50% was achieved in patients with skin tuberculosis on the basis of a high ratio between antibody titres for the whole antigen and its TB23 epitope."} {"id": "PMID:1283127", "title": "Histological diagnosis of human papillomavirus (HPV)-related dysplasia: quality control by in situ hybridization (ISH) analysis.", "content": "The Authors studied 54 cervical biopsies using in situ hybridization (ISH) to identify HPV related lesions. 26 biopsies lacked clear cut koilocytotic atypia on histological examination and 28 had a diagnosis of grades 1 and 2 intraepithelial neoplasia. Histological diagnosis of HPV-related dysplasia were studied using ISH with biotinylated probes (Phatogene DNA probe assay Enzo Diagnostics). Probes included HPV types 6/11, 16/18 and 31/35/51. HPV DNA were detected in 18 of 28 (64.3%) cervical biopsies with diagnosis of grade 1 and grade 2 cervical intraepithelial neoplasia with koilocytotic atypia. None of the 26 cervical biopsies equivocal for koilocytotic atypia had detectable HPV DNA with ISH. These results suggest that ISH can be used for the quality control in the histological diagnosis of koilocytotic atypia.", "contents": "Histological diagnosis of human papillomavirus (HPV)-related dysplasia: quality control by in situ hybridization (ISH) analysis. The Authors studied 54 cervical biopsies using in situ hybridization (ISH) to identify HPV related lesions. 26 biopsies lacked clear cut koilocytotic atypia on histological examination and 28 had a diagnosis of grades 1 and 2 intraepithelial neoplasia. Histological diagnosis of HPV-related dysplasia were studied using ISH with biotinylated probes (Phatogene DNA probe assay Enzo Diagnostics). Probes included HPV types 6/11, 16/18 and 31/35/51. HPV DNA were detected in 18 of 28 (64.3%) cervical biopsies with diagnosis of grade 1 and grade 2 cervical intraepithelial neoplasia with koilocytotic atypia. None of the 26 cervical biopsies equivocal for koilocytotic atypia had detectable HPV DNA with ISH. These results suggest that ISH can be used for the quality control in the histological diagnosis of koilocytotic atypia."} {"id": "PMID:1283128", "title": "Effect of phytanic acid on cultured retinal pigment epithelium: an in vitro model for Refsum's disease.", "content": "Refsum's disease (heredopathia atactica polyneuritiformis) is an autosomal recessive retinitis pigmentosa syndrome caused by the excessive deposition of phytanic acid in ocular tissues. It is thought that phytanic acid causes retinal degeneration either by interfering with vitamin A metabolism in the retinal pigment epithelium or by altering photoreceptor cell membrane structure. Efforts to elucidate the molecular mechanism of phytanic acid's retinal toxicity have been hampered by the rarity of human pathological specimens and by the inability to reproduce the disease in living animal models. In this study, an in vitro model for Refsum's disease was established by exposing cultured human and bovine retinal pigment epithelial cells to phytanic acid bound to bovine serum albumin at concentrations comparable to levels found in affected humans. Ultrastructural studies show that these cells exhibit morphological changes consistent with those observed in pathological specimens from patients with Refsum's disease. Biochemical assays of retinoid metabolism by cell membranes from control cells and from cells exposed to 200 microM phytanic acid demonstrate that the ability to esterify retinol and to isomerize all-trans retinoids to 11-cis retinoids remains intact despite the deposition of large amounts of phytanic acid. The work described here is strong evidence against the hypothesis that phytanic acid inhibits vitamin A metabolism in the retinal pigment epithelium, and it demonstrates the potential use of cultured retinal pigment epithelial cells in modeling this and other degenerative diseases of the retina.", "contents": "Effect of phytanic acid on cultured retinal pigment epithelium: an in vitro model for Refsum's disease. Refsum's disease (heredopathia atactica polyneuritiformis) is an autosomal recessive retinitis pigmentosa syndrome caused by the excessive deposition of phytanic acid in ocular tissues. It is thought that phytanic acid causes retinal degeneration either by interfering with vitamin A metabolism in the retinal pigment epithelium or by altering photoreceptor cell membrane structure. Efforts to elucidate the molecular mechanism of phytanic acid's retinal toxicity have been hampered by the rarity of human pathological specimens and by the inability to reproduce the disease in living animal models. In this study, an in vitro model for Refsum's disease was established by exposing cultured human and bovine retinal pigment epithelial cells to phytanic acid bound to bovine serum albumin at concentrations comparable to levels found in affected humans. Ultrastructural studies show that these cells exhibit morphological changes consistent with those observed in pathological specimens from patients with Refsum's disease. Biochemical assays of retinoid metabolism by cell membranes from control cells and from cells exposed to 200 microM phytanic acid demonstrate that the ability to esterify retinol and to isomerize all-trans retinoids to 11-cis retinoids remains intact despite the deposition of large amounts of phytanic acid. The work described here is strong evidence against the hypothesis that phytanic acid inhibits vitamin A metabolism in the retinal pigment epithelium, and it demonstrates the potential use of cultured retinal pigment epithelial cells in modeling this and other degenerative diseases of the retina."} {"id": "PMID:1283129", "title": "Crystallin gene expression in the process of lentoidogenesis in cultures of chicken lens epithelial cells.", "content": "One alpha B- and three different beta-crystallin cDNA clones were isolated from a chicken lens cDNA library by using anti-crystallin antibodies. The sequence of alpha B-crystallin cDNA showed more than 70% homology with exons of alpha B-crystallin genes of the human and hamster. Two beta-crystallin cDNAs showed almost identical sequences with previously reported chicken beta B1- and beta A3/A1-crystallin genes. The remainder showed 80% homology of sequence with bovine beta B2-crystalline cDNA. Using these newly cloned cDNAs, in addition to cDNAs of alpha A- and delta-crystallin, we examined the expression pattern of these crystallins in the process of lentoidogenesis of cultured lens epithelial cells of the chicken. All crystallins except beta-crystallins were expressed through the period of cell culture, but three beta-crystallins were expressed only after the confluent stage. These results suggest that: (1) alpha A-, alpha B- and delta-crystallin cDNAs can be used to detect differentiation of the lens epithelial cell; and (2) beta-crystallin cDNAs are superior in the detection of chicken lens fibre differentiation in vitro to delta-crystallin cDNA, which is ectopically expressed by various non-lenticular tissues.", "contents": "Crystallin gene expression in the process of lentoidogenesis in cultures of chicken lens epithelial cells. One alpha B- and three different beta-crystallin cDNA clones were isolated from a chicken lens cDNA library by using anti-crystallin antibodies. The sequence of alpha B-crystallin cDNA showed more than 70% homology with exons of alpha B-crystallin genes of the human and hamster. Two beta-crystallin cDNAs showed almost identical sequences with previously reported chicken beta B1- and beta A3/A1-crystallin genes. The remainder showed 80% homology of sequence with bovine beta B2-crystalline cDNA. Using these newly cloned cDNAs, in addition to cDNAs of alpha A- and delta-crystallin, we examined the expression pattern of these crystallins in the process of lentoidogenesis of cultured lens epithelial cells of the chicken. All crystallins except beta-crystallins were expressed through the period of cell culture, but three beta-crystallins were expressed only after the confluent stage. These results suggest that: (1) alpha A-, alpha B- and delta-crystallin cDNAs can be used to detect differentiation of the lens epithelial cell; and (2) beta-crystallin cDNAs are superior in the detection of chicken lens fibre differentiation in vitro to delta-crystallin cDNA, which is ectopically expressed by various non-lenticular tissues."} {"id": "PMID:1283137", "title": "Effect of sucralfate on gastric mucosal calcium channels activity.", "content": "1. The effect of anti-ulcer agent, sucralfate, on the activity of the gastric mucosal calcium channel was investigated using calcium channels purified from rat gastric epithelial cell membranes. 2. The channels on reconstitution into phosphatidylcholine vesicles responded in a concentration-dependent manner to a calcium channel activator, BAY K8644, as well as to a calcium channel antagonist, PN200-110. The 45Ca2+ uptake was inhibited by sucralfate. Maximum inhibitory effect was attained at 100 micrograms/ml sucralfate, at which point a 52% decrease in the uptake occurred. 3. EGF-induced channel protein phosphorylation showed an increase in tyrosine phosphorylation of 55 and 170 kDa proteins, and the vesicles containing the phosphorylated channels displayed a 48% greater 45Ca2+ uptake. This phosphorylation process was inhibited by sucralfate. Furthermore, sucralfate also interfered with the binding of EGF to calcium channel protein. 4. The results indicate that sucralfate protects the cellular integrity from calcium imbalance by modulating the EGF-stimulated gastric mucosal calcium channel phosphorylation.", "contents": "Effect of sucralfate on gastric mucosal calcium channels activity. 1. The effect of anti-ulcer agent, sucralfate, on the activity of the gastric mucosal calcium channel was investigated using calcium channels purified from rat gastric epithelial cell membranes. 2. The channels on reconstitution into phosphatidylcholine vesicles responded in a concentration-dependent manner to a calcium channel activator, BAY K8644, as well as to a calcium channel antagonist, PN200-110. The 45Ca2+ uptake was inhibited by sucralfate. Maximum inhibitory effect was attained at 100 micrograms/ml sucralfate, at which point a 52% decrease in the uptake occurred. 3. EGF-induced channel protein phosphorylation showed an increase in tyrosine phosphorylation of 55 and 170 kDa proteins, and the vesicles containing the phosphorylated channels displayed a 48% greater 45Ca2+ uptake. This phosphorylation process was inhibited by sucralfate. Furthermore, sucralfate also interfered with the binding of EGF to calcium channel protein. 4. The results indicate that sucralfate protects the cellular integrity from calcium imbalance by modulating the EGF-stimulated gastric mucosal calcium channel phosphorylation."} {"id": "PMID:1283138", "title": "Effect of vitamin A on hexachlorocyclohexane (HCH) toxicity in the rat.", "content": "1. Technical hexachlorocyclohexane (HCH) depleted hepatic stores of vitamin A in male albino rats to cause secondary vitamin A deficiency. 2. Toxicity of HCH in rats is augmented by dietary vitamin A-deficiency as evidenced by growth retardation, organ hypertrophies and alterations in the serum and liver levels of the marker enzymes of toxicity. 3. Supplementation of dietary vitamin A to the rats either in adequate (2000 IU/kg diet) or in an excess but not hypervitaminotic level (10(5) IU/kg diet) resulted in significant protection against the toxicity of HCH. 4. The activities of the hepatic xenobiotic metabolizing enzymes were generally low (with the exception of glutathione S-transferase) in the vitamin A-deficient rats compared to those of the vitamin A supplemented diet groups. 5. The results indicated that dietary vitamin A influences the response of male albino rats to HCH toxicity possibly by modulating the activities of hepatic xenobiotic metabolizing enzymes.", "contents": "Effect of vitamin A on hexachlorocyclohexane (HCH) toxicity in the rat. 1. Technical hexachlorocyclohexane (HCH) depleted hepatic stores of vitamin A in male albino rats to cause secondary vitamin A deficiency. 2. Toxicity of HCH in rats is augmented by dietary vitamin A-deficiency as evidenced by growth retardation, organ hypertrophies and alterations in the serum and liver levels of the marker enzymes of toxicity. 3. Supplementation of dietary vitamin A to the rats either in adequate (2000 IU/kg diet) or in an excess but not hypervitaminotic level (10(5) IU/kg diet) resulted in significant protection against the toxicity of HCH. 4. The activities of the hepatic xenobiotic metabolizing enzymes were generally low (with the exception of glutathione S-transferase) in the vitamin A-deficient rats compared to those of the vitamin A supplemented diet groups. 5. The results indicated that dietary vitamin A influences the response of male albino rats to HCH toxicity possibly by modulating the activities of hepatic xenobiotic metabolizing enzymes."} {"id": "PMID:1283139", "title": "A pharmacological profile of glycopyrrolate: interactions at the muscarinic acetylcholine receptor.", "content": "1. Glycopyrrolate, a synthetic quaternary ammonium compound had biphasic effects on the contraction of guinea-pig atrium. At concentrations between 0.4 and 20 microM, glycopyrrolate induced a small but consistent increase in the contraction force. 2. Further increase in the concentration of glycopyrrolate produced a concentration-dependent reduction in the force of contraction with a EC50 of 0.24 mM. 3. This negative inotropic effect was opposed by a Ca2+ channel agonist, Bay K 8644. Glycopyrrolate also antagonized potently the depressant effects of carbachol and acetylcholine in guinea-pig atrium. 4. Schild analysis showed a pA2 value of 8.16 against carbachol and 8.39 against acetylcholine. These similar pA2 values suggested that both compounds may have a common interacting site. The interactions however cannot be explained by a simple competition model as the slopes of the Schild plots were larger than unity. 5. The mutual competition between glycopyrrolate and quinuclidinyl benzilate (QNB), gallamine or methoctramine indicated that glycopyrrolate could have multiple action sites in the atrium. Interaction at an allosteric site was implicated. 6. Radioligand binding studies showed that glycopyrrolate displaced pirenzepine (PZ) and AF-DX 384 from their binding to the M1 and M2 muscarinic receptors in guinea-pig brain membranes respectively. 7. The respective binding constants (Kis) were 0.60 and 0.03 nM. The Hill coefficient value (nH) for glycopyrrolate against [3H] PZ was larger than unity, suggesting positive cooperativity at the receptor complex. In contrast, the nH of the agonist [3H] AF-DX 384 was not different from unity, indicating a simple competitive inhibition. 8. Our results confirm the antimuscarinic properties of glycopyrrolate.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "A pharmacological profile of glycopyrrolate: interactions at the muscarinic acetylcholine receptor. 1. Glycopyrrolate, a synthetic quaternary ammonium compound had biphasic effects on the contraction of guinea-pig atrium. At concentrations between 0.4 and 20 microM, glycopyrrolate induced a small but consistent increase in the contraction force. 2. Further increase in the concentration of glycopyrrolate produced a concentration-dependent reduction in the force of contraction with a EC50 of 0.24 mM. 3. This negative inotropic effect was opposed by a Ca2+ channel agonist, Bay K 8644. Glycopyrrolate also antagonized potently the depressant effects of carbachol and acetylcholine in guinea-pig atrium. 4. Schild analysis showed a pA2 value of 8.16 against carbachol and 8.39 against acetylcholine. These similar pA2 values suggested that both compounds may have a common interacting site. The interactions however cannot be explained by a simple competition model as the slopes of the Schild plots were larger than unity. 5. The mutual competition between glycopyrrolate and quinuclidinyl benzilate (QNB), gallamine or methoctramine indicated that glycopyrrolate could have multiple action sites in the atrium. Interaction at an allosteric site was implicated. 6. Radioligand binding studies showed that glycopyrrolate displaced pirenzepine (PZ) and AF-DX 384 from their binding to the M1 and M2 muscarinic receptors in guinea-pig brain membranes respectively. 7. The respective binding constants (Kis) were 0.60 and 0.03 nM. The Hill coefficient value (nH) for glycopyrrolate against [3H] PZ was larger than unity, suggesting positive cooperativity at the receptor complex. In contrast, the nH of the agonist [3H] AF-DX 384 was not different from unity, indicating a simple competitive inhibition. 8. Our results confirm the antimuscarinic properties of glycopyrrolate.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283140", "title": "Effects of antiepileptic drugs, calcium channel blockers and other compounds on seizures induced by activation of voltage-dependent L calcium channel in DBA/2 mice.", "content": "1. The convulsant activity of the calcium voltage L-channel agonist Bay k 8644 was studied in genetically epilepsy prone DBA/2 mice. 2. Seizures were induced by intracerebroventricular injection of Bay k 8644. 3. These seizures were reversed by some calcium channel blockers such as dihydropyridines, some excitatory amino acid antagonists such as 2-amino-7-phosphonoeptanoate and CPPene, 2-chloro-adenosine, some anticonvulsant drugs such as magnesium valproate, diazepam and clonazepam and two kappa opioid agonists (U-50488H and U-54494A). 4. The remaining antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and trimethadione) were ineffective in this respect. Other anticonvulsant compounds such as dizocilpine (MK 801), ketamine and drugs enhancing GABAergic transmission did not significantly affect the clonic phase of the seizures induced by Bay k 8644. 5. These results show that Bay k 8644 seizures are relatively resistant to some anticonvulsant compounds. The role of some neurotransmitters on seizures induced by Bay k 8644 is discussed.", "contents": "Effects of antiepileptic drugs, calcium channel blockers and other compounds on seizures induced by activation of voltage-dependent L calcium channel in DBA/2 mice. 1. The convulsant activity of the calcium voltage L-channel agonist Bay k 8644 was studied in genetically epilepsy prone DBA/2 mice. 2. Seizures were induced by intracerebroventricular injection of Bay k 8644. 3. These seizures were reversed by some calcium channel blockers such as dihydropyridines, some excitatory amino acid antagonists such as 2-amino-7-phosphonoeptanoate and CPPene, 2-chloro-adenosine, some anticonvulsant drugs such as magnesium valproate, diazepam and clonazepam and two kappa opioid agonists (U-50488H and U-54494A). 4. The remaining antiepileptic drugs (carbamazepine, phenytoin, phenobarbital and trimethadione) were ineffective in this respect. Other anticonvulsant compounds such as dizocilpine (MK 801), ketamine and drugs enhancing GABAergic transmission did not significantly affect the clonic phase of the seizures induced by Bay k 8644. 5. These results show that Bay k 8644 seizures are relatively resistant to some anticonvulsant compounds. The role of some neurotransmitters on seizures induced by Bay k 8644 is discussed."} {"id": "PMID:1283141", "title": "The lymphoproliferative disease virus of turkeys represents a distinct class of avian type-C retrovirus.", "content": "The lymphoproliferative disease virus of turkeys (LPDV) is the etiological agent of a rapidly developing lymphoproliferative process in turkeys. To better understand the genetic relationships of LPDV to other retroviruses we determined the nucleotide sequence of its pol gene. Comparative computer analyses of the deduced amino acid sequences of the reverse transcriptase and integrase domains within pol established that LPDV represents a distinct class of avian retroviruses that is most closely related to the avian leukemia-sarcoma viruses.", "contents": "The lymphoproliferative disease virus of turkeys represents a distinct class of avian type-C retrovirus. The lymphoproliferative disease virus of turkeys (LPDV) is the etiological agent of a rapidly developing lymphoproliferative process in turkeys. To better understand the genetic relationships of LPDV to other retroviruses we determined the nucleotide sequence of its pol gene. Comparative computer analyses of the deduced amino acid sequences of the reverse transcriptase and integrase domains within pol established that LPDV represents a distinct class of avian retroviruses that is most closely related to the avian leukemia-sarcoma viruses."} {"id": "PMID:1283142", "title": "Analysis of the gene encoding a 16-kDa proteolipid subunit of the vacuolar H(+)-ATPase from Manduca sexta midgut and tubules.", "content": "Vacuolar ATPases (V-ATPases), originally characterised as components of endomembranes, have also been implicated in epithelial ion transport, both in vertebrates and in insects. The ATPase is particularly noteworthy in lepidopteran larvae, where it generates large transepithelial potential differences and short-circuit currents across the midgut epithelium. A cDNA library from Manduca sexta larval midguts and Malpighian tubules was screened with a Drosophila melanogaster cDNA encoding the 16-kDa proteolipid subunit of the V-ATPase, and a 1.4-kb cDNA sequenced in its entirety. The sequence contains a long open reading frame, encoding a putative peptide of 156 amino acids (aa) and with an M(r) of 15,967, in close agreement with values previously suggested by sodium dodecyl sulfate-polyacrylamide gels of M. sexta midgut proteins. Correspondence of the deduced aa sequence with those of other species, particularly D. melanogaster, was extremely close. Northern blots of M. sexta midgut mRNA at high stringency revealed two transcripts of 1.4 and 1.9 kb, whereas genomic Southern blots suggest that there is only a single copy of the gene in M. sexta. The possibility that members of the 16-kDa gene family might serve multiple roles in transport and membrane communication is discussed.", "contents": "Analysis of the gene encoding a 16-kDa proteolipid subunit of the vacuolar H(+)-ATPase from Manduca sexta midgut and tubules. Vacuolar ATPases (V-ATPases), originally characterised as components of endomembranes, have also been implicated in epithelial ion transport, both in vertebrates and in insects. The ATPase is particularly noteworthy in lepidopteran larvae, where it generates large transepithelial potential differences and short-circuit currents across the midgut epithelium. A cDNA library from Manduca sexta larval midguts and Malpighian tubules was screened with a Drosophila melanogaster cDNA encoding the 16-kDa proteolipid subunit of the V-ATPase, and a 1.4-kb cDNA sequenced in its entirety. The sequence contains a long open reading frame, encoding a putative peptide of 156 amino acids (aa) and with an M(r) of 15,967, in close agreement with values previously suggested by sodium dodecyl sulfate-polyacrylamide gels of M. sexta midgut proteins. Correspondence of the deduced aa sequence with those of other species, particularly D. melanogaster, was extremely close. Northern blots of M. sexta midgut mRNA at high stringency revealed two transcripts of 1.4 and 1.9 kb, whereas genomic Southern blots suggest that there is only a single copy of the gene in M. sexta. The possibility that members of the 16-kDa gene family might serve multiple roles in transport and membrane communication is discussed."} {"id": "PMID:1283143", "title": "Radiation enhancement of laser palliation for malignant dysphagia: a pilot study.", "content": "Laser therapy offers rapid relief of dysphagia for patients with cancers of the oesophagus and gastric cardia but repeat treatments are required approximately every five weeks to maintain good swallowing. To try to prolong the treatment interval, 22 elderly patients were given additional external beam radiotherapy. Nine had squamous cell carcinoma and 13 adenocarcinoma: five had documented metastases. Six received 40 Gy and 16,30 Gy in 10-20 fractions. A 'check' endoscopy was performed three weeks after external beam radiotherapy. Dysphagia was graded from 0-4 (0 = normal; 4 = dysphagia for liquids). The median dysphagia grade improved from 3 to 1 after laser treatment. This improvement was maintained in the 30 Gy group but there was a noticeable deterioration in three of those who had received the higher radiation dose. A lifelong dysphagia grade of 2 or better was enjoyed by 14 of 16 patients in the 30 Gy group but only two of six in the 40 Gy group. The dysphagia controlled interval was 9 weeks (median) after check endoscopy and subsequent endoscopic procedures were required every 13 weeks to maintain good swallowing. There were no endoscopy related complications. Combined treatment is a promising approach for reducing the frequency of endoscopic treatments. The 30 Gy dose seems more appropriate and may prolong survival. A randomised study to test these conclusions is in progress.", "contents": "Radiation enhancement of laser palliation for malignant dysphagia: a pilot study. Laser therapy offers rapid relief of dysphagia for patients with cancers of the oesophagus and gastric cardia but repeat treatments are required approximately every five weeks to maintain good swallowing. To try to prolong the treatment interval, 22 elderly patients were given additional external beam radiotherapy. Nine had squamous cell carcinoma and 13 adenocarcinoma: five had documented metastases. Six received 40 Gy and 16,30 Gy in 10-20 fractions. A 'check' endoscopy was performed three weeks after external beam radiotherapy. Dysphagia was graded from 0-4 (0 = normal; 4 = dysphagia for liquids). The median dysphagia grade improved from 3 to 1 after laser treatment. This improvement was maintained in the 30 Gy group but there was a noticeable deterioration in three of those who had received the higher radiation dose. A lifelong dysphagia grade of 2 or better was enjoyed by 14 of 16 patients in the 30 Gy group but only two of six in the 40 Gy group. The dysphagia controlled interval was 9 weeks (median) after check endoscopy and subsequent endoscopic procedures were required every 13 weeks to maintain good swallowing. There were no endoscopy related complications. Combined treatment is a promising approach for reducing the frequency of endoscopic treatments. The 30 Gy dose seems more appropriate and may prolong survival. A randomised study to test these conclusions is in progress."} {"id": "PMID:1283144", "title": "Endoscopic palliation for inoperable malignant dysphagia: long term follow up.", "content": "This prospective non-randomised trial of 128 selected patients with unresectable oesophageal or gastrooesophageal junction cancers aims to evaluate the initial relief of malignant obstruction by means of bipolar electrocoagulation for both circumferential and submucosal strictures of Nd:YAG laser for the other patients. A limited dilatation was performed initially if a small calibre endoscope was unable to pass through the stricture. Prompt and significant relief of dysphagia without complications was achieved in 83% of patients. Improved patients were retreated monthly during the follow up period. Radiotherapy was recommended when possible. Symptomatic relief of obstruction lasted 4.2 months on average and 76% of patients remained palliated until death. Monthly retreatment using the most appropriate endoscopic procedure for the tumour configuration and radiotherapy after endoscopic relief of obstruction seems to give the best palliation for patients with unresectable cancers of the oesophagus or gastrooesophageal junction.", "contents": "Endoscopic palliation for inoperable malignant dysphagia: long term follow up. This prospective non-randomised trial of 128 selected patients with unresectable oesophageal or gastrooesophageal junction cancers aims to evaluate the initial relief of malignant obstruction by means of bipolar electrocoagulation for both circumferential and submucosal strictures of Nd:YAG laser for the other patients. A limited dilatation was performed initially if a small calibre endoscope was unable to pass through the stricture. Prompt and significant relief of dysphagia without complications was achieved in 83% of patients. Improved patients were retreated monthly during the follow up period. Radiotherapy was recommended when possible. Symptomatic relief of obstruction lasted 4.2 months on average and 76% of patients remained palliated until death. Monthly retreatment using the most appropriate endoscopic procedure for the tumour configuration and radiotherapy after endoscopic relief of obstruction seems to give the best palliation for patients with unresectable cancers of the oesophagus or gastrooesophageal junction."} {"id": "PMID:1283145", "title": "Extraluminal hyperechogenic echo detected by transvaginal ultrasonography as a prognostic factor in recurrent hydatidiform mole.", "content": "Measuring beta hCG titers by either bioassay or radioimmunoassay has become the cornerstone in the management and treatment of hydatidiform mole. It is this very determination which will indicate either spontaneous remission or the need for chemotherapy treatment due to rising or plateauing titers. Herein, we report on the potential assistance of a unique ultrasonographic appearance of a hyperechogenic shadow located in the uterine wall, before and after an attempt for full evacuation of hydatidiform mole. The behavior of this echogenic area was more sensitive in predicting the course of the disease than did the beta hCG titers. Thus, using transvaginal sonography may serve as another predictor and indicator in evaluating the treatment of hydatidiform mole.", "contents": "Extraluminal hyperechogenic echo detected by transvaginal ultrasonography as a prognostic factor in recurrent hydatidiform mole. Measuring beta hCG titers by either bioassay or radioimmunoassay has become the cornerstone in the management and treatment of hydatidiform mole. It is this very determination which will indicate either spontaneous remission or the need for chemotherapy treatment due to rising or plateauing titers. Herein, we report on the potential assistance of a unique ultrasonographic appearance of a hyperechogenic shadow located in the uterine wall, before and after an attempt for full evacuation of hydatidiform mole. The behavior of this echogenic area was more sensitive in predicting the course of the disease than did the beta hCG titers. Thus, using transvaginal sonography may serve as another predictor and indicator in evaluating the treatment of hydatidiform mole."} {"id": "PMID:1283146", "title": "[Effect of aprotinin on fibrosis of nerve sutures].", "content": "Although fibrin-glue has been used in many areas of surgery, it has not become fully established in nerve coaptation. Initially, significant advantages were expected; however, as the fibrin clot dissolved prematurely and gapping occurred, antifibrinolytic substances were added to the glue. Following this procedure, fibroses occurred frequently, which remains a problem. In this study, the influence of aprotinin's fibrosis-inducing effect was investigated. Aprotinin demonstrated no additional fibrosis-promoting effect.", "contents": "[Effect of aprotinin on fibrosis of nerve sutures]. Although fibrin-glue has been used in many areas of surgery, it has not become fully established in nerve coaptation. Initially, significant advantages were expected; however, as the fibrin clot dissolved prematurely and gapping occurred, antifibrinolytic substances were added to the glue. Following this procedure, fibroses occurred frequently, which remains a problem. In this study, the influence of aprotinin's fibrosis-inducing effect was investigated. Aprotinin demonstrated no additional fibrosis-promoting effect."} {"id": "PMID:1283147", "title": "[A severe skin reaction following mexiletene].", "content": "A 70-year-old man was treated with oral mexiletene because of ventricular premature beats due to ischemic heart disease. He developed a severe maculopapular rash which did not respond to antiallergic treatment, but disappeared after discontinuation of the drug. Adverse effects on the central nervous, cardiovascular and gastrointestinal systems have been described. A rash is rare, and in our case was of unusual severity.", "contents": "[A severe skin reaction following mexiletene]. A 70-year-old man was treated with oral mexiletene because of ventricular premature beats due to ischemic heart disease. He developed a severe maculopapular rash which did not respond to antiallergic treatment, but disappeared after discontinuation of the drug. Adverse effects on the central nervous, cardiovascular and gastrointestinal systems have been described. A rash is rare, and in our case was of unusual severity."} {"id": "PMID:1283148", "title": "The spectrum of CFTR mutations in south-west German cystic fibrosis patients.", "content": "The cystic fibrosis transmembrane conductance regulator (CFTR) gene of 110 cystic fibrosis (CF) patients from the south-west of Germany was screened for 12 different mutations. This analysis resulted in an identification of 79% of all CF mutations and a complete genotype in 66% of the families. The most common mutation found was delta F508 (67%). Another 5 mutations accounted for a further 12.5% (4% G542X; 3% R553X; 3% N1303K; 2% 1717-1 G-->A; 0.5% G551D) whereas 6 mutations (R117H, A455E, delta I507, S549I, S549N, and R1162X) were not found. Fifty-four (49%) patients were delta F508 homozygotes and 18 (16.5%) were compound heterozygotes for delta F508 and one of the rarer mutations. These frequencies differ slightly from those found in the north of Germany and considerably from those reported from the south of Europe, which seems to be consistent with a north to south decline of the relative abundance of delta F508. Two patients, age 6 and 25 years, were compound heterozygotes for G542X and N1303K. The clinical features of the 6 year old were characterised by severe gastrointestinal and as yet only mild pulmonary complications whereas the 25 year old manifested severe pulmonary and gastrointestinal symptoms indicating that the N1303K mutation of the C-terminal CFTR nucleotide binding fold significantly impairs protein function in both the pancreas and the lungs.", "contents": "The spectrum of CFTR mutations in south-west German cystic fibrosis patients. The cystic fibrosis transmembrane conductance regulator (CFTR) gene of 110 cystic fibrosis (CF) patients from the south-west of Germany was screened for 12 different mutations. This analysis resulted in an identification of 79% of all CF mutations and a complete genotype in 66% of the families. The most common mutation found was delta F508 (67%). Another 5 mutations accounted for a further 12.5% (4% G542X; 3% R553X; 3% N1303K; 2% 1717-1 G-->A; 0.5% G551D) whereas 6 mutations (R117H, A455E, delta I507, S549I, S549N, and R1162X) were not found. Fifty-four (49%) patients were delta F508 homozygotes and 18 (16.5%) were compound heterozygotes for delta F508 and one of the rarer mutations. These frequencies differ slightly from those found in the north of Germany and considerably from those reported from the south of Europe, which seems to be consistent with a north to south decline of the relative abundance of delta F508. Two patients, age 6 and 25 years, were compound heterozygotes for G542X and N1303K. The clinical features of the 6 year old were characterised by severe gastrointestinal and as yet only mild pulmonary complications whereas the 25 year old manifested severe pulmonary and gastrointestinal symptoms indicating that the N1303K mutation of the C-terminal CFTR nucleotide binding fold significantly impairs protein function in both the pancreas and the lungs."} {"id": "PMID:1283149", "title": "A termination mutation (2143delT) in the CFTR gene of German cystic fibrosis patients.", "content": "German patients with cystic fibrosis (CF) were screened for molecular lesions in exon 13 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by single strand conformation polymorphism (SSCP) and chemical cleavage of mismatch analyses. Direct sequencing of four samples that displayed the same SSCP pattern and that were susceptible to cleavage of hetero-duplexes by osmium tetroxide revealed, in all cases, a deletion of a single T residue at nucleotide position 2143 within codon 671 of the CFTR gene. As a result, leucine codon 671 is changed into a termination codon. In total, the 2143delT mutation was confirmed in 6 out of 271 German non-delta F508 CF chromosomes by artificial restriction fragment length polymorphism analysis, indicating that this frameshift mutation accounts for about 2% of German non-delta F508 mutations. The 6 pancreas insufficient patients who are compound heterozygous for 2143-delT suffer from the typical features of pulmonary and gastrointestinal CF disease. The 2143delT mutation completes the panel of the more frequent CFTR mutations that reside on the \"delta F508 haplotype\" and that contribute to its overpresentation among German non-delta F508 alleles that are associated with severe forms of disease.", "contents": "A termination mutation (2143delT) in the CFTR gene of German cystic fibrosis patients. German patients with cystic fibrosis (CF) were screened for molecular lesions in exon 13 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene by single strand conformation polymorphism (SSCP) and chemical cleavage of mismatch analyses. Direct sequencing of four samples that displayed the same SSCP pattern and that were susceptible to cleavage of hetero-duplexes by osmium tetroxide revealed, in all cases, a deletion of a single T residue at nucleotide position 2143 within codon 671 of the CFTR gene. As a result, leucine codon 671 is changed into a termination codon. In total, the 2143delT mutation was confirmed in 6 out of 271 German non-delta F508 CF chromosomes by artificial restriction fragment length polymorphism analysis, indicating that this frameshift mutation accounts for about 2% of German non-delta F508 mutations. The 6 pancreas insufficient patients who are compound heterozygous for 2143-delT suffer from the typical features of pulmonary and gastrointestinal CF disease. The 2143delT mutation completes the panel of the more frequent CFTR mutations that reside on the \"delta F508 haplotype\" and that contribute to its overpresentation among German non-delta F508 alleles that are associated with severe forms of disease."} {"id": "PMID:1283150", "title": "Assessment of iduronate-2-sulfatase mRNA expression in Hunter syndrome (mucopolysaccharidosis type II).", "content": "Eight unrelated patients with Hunter syndrome were investigated for expression of iduronate-2-sulfatase (IDS) mRNA by reverse transcription (RT) linked to polymerase chain reaction (PCR), or RT-PCR. The entire coding region was studied by amplification of two overlapping segments of 0.7 and 1.1 kb. Seven children with Hunter syndrome had PCR products indistinguishable in size from normal. One patient, with clinically severe disease, did not produce either IDS product although mRNA for a control gene was readily amplified. This method rapidly identifies patients having absent or qualitatively abnormal IDS mRNA and may be useful in investigating genotype-phenotype relationships.", "contents": "Assessment of iduronate-2-sulfatase mRNA expression in Hunter syndrome (mucopolysaccharidosis type II). Eight unrelated patients with Hunter syndrome were investigated for expression of iduronate-2-sulfatase (IDS) mRNA by reverse transcription (RT) linked to polymerase chain reaction (PCR), or RT-PCR. The entire coding region was studied by amplification of two overlapping segments of 0.7 and 1.1 kb. Seven children with Hunter syndrome had PCR products indistinguishable in size from normal. One patient, with clinically severe disease, did not produce either IDS product although mRNA for a control gene was readily amplified. This method rapidly identifies patients having absent or qualitatively abnormal IDS mRNA and may be useful in investigating genotype-phenotype relationships."} {"id": "PMID:1283151", "title": "A novel CFTR mutation, 4035delA, detected by non-radioactive SSCP analysis.", "content": "German cystic fibrosis patients were screened for mutations in exon 21 of the cystic fibrosis transmembrane conductance regulator gene by a non-radioactive variation of the single-strand conformation polymorphism technique. Asymmetric polymerase chain reaction amplification was used to produce single strands of exon-containing genomic sequences that were analyzed on polyacrylamide gels subsequently stained with ethidium bromide. This rapid technique led to the identification of a novel mutation, a 1-bp deletion at position 4035(A) of the cDNA sequence. The patient, who is also heterozygous for the delta F508 mutation, exhibits an intermediate form of the disease.", "contents": "A novel CFTR mutation, 4035delA, detected by non-radioactive SSCP analysis. German cystic fibrosis patients were screened for mutations in exon 21 of the cystic fibrosis transmembrane conductance regulator gene by a non-radioactive variation of the single-strand conformation polymorphism technique. Asymmetric polymerase chain reaction amplification was used to produce single strands of exon-containing genomic sequences that were analyzed on polyacrylamide gels subsequently stained with ethidium bromide. This rapid technique led to the identification of a novel mutation, a 1-bp deletion at position 4035(A) of the cDNA sequence. The patient, who is also heterozygous for the delta F508 mutation, exhibits an intermediate form of the disease."} {"id": "PMID:1283154", "title": "Cultured human cord blood cells spontaneously produce a factor with basophil-promoting activity.", "content": "Cord blood is a source for pluripotential stem cells capable of differentiating into various hemopoietic cell lines in the presence of suitable specific growth factors. Without additional growth factors, cultured cord blood cells give rise to large numbers of basophils. We have recently defined a human basophil growth promoting factor, designated as interleukin-3-like activity (IL-3-LA), produced spontaneously by human monocytes and lymphocytes. In order to explain the phenomenon of spontaneous basophil development in cord blood cultures, we studied the relationship between basophil production and IL-3-LA release in these cultures. IL-3-LA produced by cord blood mononuclear cells increased from day 3 to day 14 and then decreased gradually by day 35. Basophil development was observed from day 14 on (33% +/- 6.4) and peaked on day 21 (51% +/- 7.4). Histamine release followed the same pattern i.e., 10 +/- 3.4 ng/ml on day 14, and 23 +/- 6.5 ng/ml on day 21. It is suggested that IL-3-LA spontaneously released by cord blood mononuclear cells induces basophil development in these cultures.", "contents": "Cultured human cord blood cells spontaneously produce a factor with basophil-promoting activity. Cord blood is a source for pluripotential stem cells capable of differentiating into various hemopoietic cell lines in the presence of suitable specific growth factors. Without additional growth factors, cultured cord blood cells give rise to large numbers of basophils. We have recently defined a human basophil growth promoting factor, designated as interleukin-3-like activity (IL-3-LA), produced spontaneously by human monocytes and lymphocytes. In order to explain the phenomenon of spontaneous basophil development in cord blood cultures, we studied the relationship between basophil production and IL-3-LA release in these cultures. IL-3-LA produced by cord blood mononuclear cells increased from day 3 to day 14 and then decreased gradually by day 35. Basophil development was observed from day 14 on (33% +/- 6.4) and peaked on day 21 (51% +/- 7.4). Histamine release followed the same pattern i.e., 10 +/- 3.4 ng/ml on day 14, and 23 +/- 6.5 ng/ml on day 21. It is suggested that IL-3-LA spontaneously released by cord blood mononuclear cells induces basophil development in these cultures."} {"id": "PMID:1283152", "title": "Cytoplasmic expression of a CD24-related epitope in human PHA activated normal T lymphocytes.", "content": "In this study we have analysed by immunoperoxidase (IPx) and indirect immunofluorescence (IIF) the intracellular and cell surface reactivity of VIB-E3 mAb, previously clustered as anti-CD24 antigen, on resting and activated normal human T lymphocytes. By IPx assay VIB-E3 mAb did not show reactivity with normal resting T cells. In contrast, the analysis of 11 different samples of PHA activated normal mononuclear cells, showed an intracytoplasmic expression of CD24. Kinetic studies showed that CD24 appears 24 to 48 h after PHA stimulation. To our knowledge, this is the first evidence that a CD24-related epitope is expressed in normal activated T lymphocytes.", "contents": "Cytoplasmic expression of a CD24-related epitope in human PHA activated normal T lymphocytes. In this study we have analysed by immunoperoxidase (IPx) and indirect immunofluorescence (IIF) the intracellular and cell surface reactivity of VIB-E3 mAb, previously clustered as anti-CD24 antigen, on resting and activated normal human T lymphocytes. By IPx assay VIB-E3 mAb did not show reactivity with normal resting T cells. In contrast, the analysis of 11 different samples of PHA activated normal mononuclear cells, showed an intracytoplasmic expression of CD24. Kinetic studies showed that CD24 appears 24 to 48 h after PHA stimulation. To our knowledge, this is the first evidence that a CD24-related epitope is expressed in normal activated T lymphocytes."} {"id": "PMID:1283155", "title": "Reactive oxygen species modified DNA fragments of varying size are the preferred antigen for human anti-DNA autoantibodies.", "content": "In vitro studies were carried out to determine if reactive oxygen species modified DNA molecules are the preferred antigen for anti-DNA antibodies found in SLE sera. Reactive oxygen species were generated by 254 nm irradiation of hydrogen peroxide. Single stranded breaks, decrease in Tm and modification of adenine (21.7%) and thymine (48%) were the major effects observed on native DNA fragments of 300 bp in length. The ROS-modified DNA showed increased binding with naturally occurring anti-DNA autoantibodies as compared to unmodified DNA fragments. These results were substantiated by competition ELISA. Measurement of binding with DNA fragments of varying size revealed considerably increased binding as the fragment size increased from 50 bp to 800 bp. The relative affinity of anti-DNA IgG for ROS-modified and native DNA fragments of 300 bp were in the order of 6.26 x 10(-8) M and 4.07 x 10(-8) M, respectively.", "contents": "Reactive oxygen species modified DNA fragments of varying size are the preferred antigen for human anti-DNA autoantibodies. In vitro studies were carried out to determine if reactive oxygen species modified DNA molecules are the preferred antigen for anti-DNA antibodies found in SLE sera. Reactive oxygen species were generated by 254 nm irradiation of hydrogen peroxide. Single stranded breaks, decrease in Tm and modification of adenine (21.7%) and thymine (48%) were the major effects observed on native DNA fragments of 300 bp in length. The ROS-modified DNA showed increased binding with naturally occurring anti-DNA autoantibodies as compared to unmodified DNA fragments. These results were substantiated by competition ELISA. Measurement of binding with DNA fragments of varying size revealed considerably increased binding as the fragment size increased from 50 bp to 800 bp. The relative affinity of anti-DNA IgG for ROS-modified and native DNA fragments of 300 bp were in the order of 6.26 x 10(-8) M and 4.07 x 10(-8) M, respectively."} {"id": "PMID:1283153", "title": "CD5 and immunoglobulin VH gene expression in B-cell lines from patients with autoimmune diseases.", "content": "We studied the CD5 mRNA expression and VH gene family usage in Epstein-Barr virus (EBV)-immortalized B-cell lines derived from the blood of patients with type 1 diabetes (IDDM) of recent onset and of patients with polyneuritis cranialis multiplex (cranial neuritis; CN). After immortalization with EBV, at least 10 cell lines from each subject were tested for surface CD5 and CD20. mRNA expression was studied using cDNA probes for the six VH families as well as for CD5. The EBV lines from the IDDM patients used the VHIV family more frequently and VHI and VHII families less frequently than lines from controls. EBV lines from CN patients expressed the VHI and VHII families more often than those of the controls. When the IDDM and CN lines were compared, the lines derived from IDDM patients were found to use VH families I and II less frequently and VH families IV and V more frequently than lines from CN patients. There were no significant differences in the mean numbers of CD5+ B cells in the cell lines tested. More than half of the lines from each patient expressed CD5 at the mRNA level. No correlation was seen between the expression of surface CD5 and the level of CD5 mRNA expression. There was, however, a positive correlation between the usage of VH families III, V and VI, and the CD5 mRNA expression. In conclusion, the usage of VH families I to VI seemed to differ in patients with IDDM and CN. No differences were seen in the surface CD5 expression, but the lines expressing CD5 mRNA preferentially used the VH families III, V and VI.", "contents": "CD5 and immunoglobulin VH gene expression in B-cell lines from patients with autoimmune diseases. We studied the CD5 mRNA expression and VH gene family usage in Epstein-Barr virus (EBV)-immortalized B-cell lines derived from the blood of patients with type 1 diabetes (IDDM) of recent onset and of patients with polyneuritis cranialis multiplex (cranial neuritis; CN). After immortalization with EBV, at least 10 cell lines from each subject were tested for surface CD5 and CD20. mRNA expression was studied using cDNA probes for the six VH families as well as for CD5. The EBV lines from the IDDM patients used the VHIV family more frequently and VHI and VHII families less frequently than lines from controls. EBV lines from CN patients expressed the VHI and VHII families more often than those of the controls. When the IDDM and CN lines were compared, the lines derived from IDDM patients were found to use VH families I and II less frequently and VH families IV and V more frequently than lines from CN patients. There were no significant differences in the mean numbers of CD5+ B cells in the cell lines tested. More than half of the lines from each patient expressed CD5 at the mRNA level. No correlation was seen between the expression of surface CD5 and the level of CD5 mRNA expression. There was, however, a positive correlation between the usage of VH families III, V and VI, and the CD5 mRNA expression. In conclusion, the usage of VH families I to VI seemed to differ in patients with IDDM and CN. No differences were seen in the surface CD5 expression, but the lines expressing CD5 mRNA preferentially used the VH families III, V and VI."} {"id": "PMID:1283156", "title": "Regulation of human T lymphoblast growth by sensory neuropeptides: augmentation of cholecystokinin-induced inhibition of Molt-4 proliferation by somatostatin and vasoactive intestinal peptide in vitro.", "content": "The effects on proliferation of Molt-4 lymphoblasts of cholecystokinin (CCK-8), somatostatin-14 (SS), vasoactive intestinal peptide (VIP) and substance P (SP) were investigated using different combinations of the peptides, peptide analogs and their antagonists. In vitro proliferation of the cells was measured by a colorimetric assay for cell growth and survival. Results indicate that SP and SP (3-11) stimulated, whereas CCK-8, VIP and SS inhibited, proliferation in a dose-dependent manner (P < 0.05). Unsulfated CCK-8 had no effect on growth of Molt-4 lymphoblasts, and a specific antagonist of CCK, at a concentration 10(-6) M, diminished the inhibitory effect of CCK-8 on Molt lymphoblasts (P < 0.05). This suggests that the inhibitory action of CCK-8 was mediated by peripheral-type CCK receptors. SS and VIP, at equimolar concentrations of 10(-6) M, significantly augmented the CCK-8-induced inhibition of Molt-4 lymphoblast proliferation. However, none of the inhibiting neuropeptides suppressed stimulation of Molt-4 lymphoblast proliferation in response to SP. These data suggest a role of sensory neuropeptides including CCK in modulating human T lymphoblast proliferation during neuroendocrine interactions with the immune system.", "contents": "Regulation of human T lymphoblast growth by sensory neuropeptides: augmentation of cholecystokinin-induced inhibition of Molt-4 proliferation by somatostatin and vasoactive intestinal peptide in vitro. The effects on proliferation of Molt-4 lymphoblasts of cholecystokinin (CCK-8), somatostatin-14 (SS), vasoactive intestinal peptide (VIP) and substance P (SP) were investigated using different combinations of the peptides, peptide analogs and their antagonists. In vitro proliferation of the cells was measured by a colorimetric assay for cell growth and survival. Results indicate that SP and SP (3-11) stimulated, whereas CCK-8, VIP and SS inhibited, proliferation in a dose-dependent manner (P < 0.05). Unsulfated CCK-8 had no effect on growth of Molt-4 lymphoblasts, and a specific antagonist of CCK, at a concentration 10(-6) M, diminished the inhibitory effect of CCK-8 on Molt lymphoblasts (P < 0.05). This suggests that the inhibitory action of CCK-8 was mediated by peripheral-type CCK receptors. SS and VIP, at equimolar concentrations of 10(-6) M, significantly augmented the CCK-8-induced inhibition of Molt-4 lymphoblast proliferation. However, none of the inhibiting neuropeptides suppressed stimulation of Molt-4 lymphoblast proliferation in response to SP. These data suggest a role of sensory neuropeptides including CCK in modulating human T lymphoblast proliferation during neuroendocrine interactions with the immune system."} {"id": "PMID:1283157", "title": "Establishment of a murine pre-B cell clone dependent on interleukin-7 and stem cell factor.", "content": "To identify cytokines required for proliferation of murine pre-B cells, we established a pre-B cell clone MH11 (B220+ MB-1+ sIgM-) on a stromal cell line ST2 from day 13 fetal liver. The growth of MH11 is dependent on ST2. Another stromal cell line PA6, non-secretor of IL-7, could not support MH11 unless IL-7 was added. We investigated the effect of cytokines on proliferation of MH11 with or without stromal cells. IL-7 had a stimulatory effect on proliferation of MH11, but IL-7 alone could not support MH11 growth without ST2. Recombinant stem cell factor (rSCF) also had a positive effect on MH11. rSCF and rIL-7, when added together, could maintain the growth of MH11 in the absence of stromal cells. Moreover, the growth of MH11 on ST2 was inhibited almost completely by anti-c-kit monoclonal antibody (mAb). These results demonstrate that direct SCF/c-kit interaction is involved in the stimulation of pre-B cells.", "contents": "Establishment of a murine pre-B cell clone dependent on interleukin-7 and stem cell factor. To identify cytokines required for proliferation of murine pre-B cells, we established a pre-B cell clone MH11 (B220+ MB-1+ sIgM-) on a stromal cell line ST2 from day 13 fetal liver. The growth of MH11 is dependent on ST2. Another stromal cell line PA6, non-secretor of IL-7, could not support MH11 unless IL-7 was added. We investigated the effect of cytokines on proliferation of MH11 with or without stromal cells. IL-7 had a stimulatory effect on proliferation of MH11, but IL-7 alone could not support MH11 growth without ST2. Recombinant stem cell factor (rSCF) also had a positive effect on MH11. rSCF and rIL-7, when added together, could maintain the growth of MH11 in the absence of stromal cells. Moreover, the growth of MH11 on ST2 was inhibited almost completely by anti-c-kit monoclonal antibody (mAb). These results demonstrate that direct SCF/c-kit interaction is involved in the stimulation of pre-B cells."} {"id": "PMID:1283158", "title": "Continuous ambulatory electrocardiography among workers exposed to methylmethacrylate.", "content": "Methylmethacrylate (MMA), a widely used monomer in the manufacture of acrylic polymers, has been reported to cause cardiac troubles in industrial workers. The effects of MMA on the heart was assessed by continuous ambulatory electrocardiographic records. The study was performed in 22 occupationally exposed workers and in 18 healthy controls. Our study did not support the hypothesis that MMA is responsible for cardiomyodystrophy. However, supraventricular and ventricular ectopic beats were significantly more frequent among exposed workers versus controls (P < 0.01). Moreover, repolarization changes such as large T waves were noted only in exposed workers (eight cases against none in the control group). Although there was no clear connection between MMA exposure and the recorded cardiac changes in the exposed group, the role of MMA cannot be totally excluded.", "contents": "Continuous ambulatory electrocardiography among workers exposed to methylmethacrylate. Methylmethacrylate (MMA), a widely used monomer in the manufacture of acrylic polymers, has been reported to cause cardiac troubles in industrial workers. The effects of MMA on the heart was assessed by continuous ambulatory electrocardiographic records. The study was performed in 22 occupationally exposed workers and in 18 healthy controls. Our study did not support the hypothesis that MMA is responsible for cardiomyodystrophy. However, supraventricular and ventricular ectopic beats were significantly more frequent among exposed workers versus controls (P < 0.01). Moreover, repolarization changes such as large T waves were noted only in exposed workers (eight cases against none in the control group). Although there was no clear connection between MMA exposure and the recorded cardiac changes in the exposed group, the role of MMA cannot be totally excluded."} {"id": "PMID:1283159", "title": "Freeze-drying of bone tissue: immunocytochemistry and enzyme histochemistry on paraffin embedded and low-temperature resin embedded specimens.", "content": "A simple protocol of tissue preparation was sought, which would enable marker enzymes of bone cells and extracellular matrix antigens to be localized in the same tissue section with high optical resolution. For this purpose, snap-frozen samples of rat fetal skeletal tissues were dried in a FDU 010 freeze-drying unit (Balzers) for 8-12 h at -50 to -40 degrees C and 0.02 bar. Freeze-dried tissues were either vacuum-infiltrated at 45 degrees C and embedded undemineralized in Paraplast, or vacuum-infiltrated overnight at 4 degrees C and embedded undemineralized in glycol methacrylate. These procedures enabled enzyme cytochemistry for alkaline phosphatase and tartrate-resistant acid phosphatase, and immunocytochemical staining for collagen types I, III, and laminin to be performed on the same sections. No pretreatment of the sections was necessary to reveal collagen antigenicity. This study reveals the possibility of complementing immunocytochemical studies of extracellular matrix with enzyme cytochemistry and, above all, with the excellent tissue preservation and high resolution afforded by plastic embedding.", "contents": "Freeze-drying of bone tissue: immunocytochemistry and enzyme histochemistry on paraffin embedded and low-temperature resin embedded specimens. A simple protocol of tissue preparation was sought, which would enable marker enzymes of bone cells and extracellular matrix antigens to be localized in the same tissue section with high optical resolution. For this purpose, snap-frozen samples of rat fetal skeletal tissues were dried in a FDU 010 freeze-drying unit (Balzers) for 8-12 h at -50 to -40 degrees C and 0.02 bar. Freeze-dried tissues were either vacuum-infiltrated at 45 degrees C and embedded undemineralized in Paraplast, or vacuum-infiltrated overnight at 4 degrees C and embedded undemineralized in glycol methacrylate. These procedures enabled enzyme cytochemistry for alkaline phosphatase and tartrate-resistant acid phosphatase, and immunocytochemical staining for collagen types I, III, and laminin to be performed on the same sections. No pretreatment of the sections was necessary to reveal collagen antigenicity. This study reveals the possibility of complementing immunocytochemical studies of extracellular matrix with enzyme cytochemistry and, above all, with the excellent tissue preservation and high resolution afforded by plastic embedding."} {"id": "PMID:1283160", "title": "Histochemical characterization of anionic constituents in oocyte-cumulus complex of rats.", "content": "Fertilization is a process that involves the recognition and adhesion of negatively charged spermatozoa to the oocyte investments. It is not known, however, if charge properties of the interacting gametes play a role in fertilization. The present study evaluates the content and distribution of anionic constituents in the oocyte-cumulus complex of rats. Polycationic colloidal gold (PCG), ruthenium red (RR) and wheat germ agglutinin (WGA) were used as cytochemical markers of anionic sites at the light (LM) and electron microscopical (EM) levels. Isolated oocyte-cumulus complexes were fixed with glutaraldehyde (GA) and OsO4 containing RR, or with GA without RR, and embedded in araldite or LR-gold. For LM, deresined, semi-thin, araldite-embedded sections were labelled with PCG intensified by silver, or with biotinylated lectins visualized by avidin-peroxidase. For EM, thin LR-gold sections were labelled with PCG, whereas RR labelling was examined in araldite sections. The zona pellucida (ZP) failed to bind any of the polycationic markers used, but intensely bound neutralized WGA. In contrast, cumulus cell membranes bound PCG but not RR, whereas the oolemma bound RR but not PCG. The results indicate that the ZP is practically devoid of negatively charged constituents, and tends to repel positively charged ligands possibly due to the presence of cationic determinants. The binding of PCG to cumulus cells probably reflects a high content of membrane-bound heparan sulphate, whereas the binding of RR to the oolema indicates the presence of membrane sialoglycoconjugates.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Histochemical characterization of anionic constituents in oocyte-cumulus complex of rats. Fertilization is a process that involves the recognition and adhesion of negatively charged spermatozoa to the oocyte investments. It is not known, however, if charge properties of the interacting gametes play a role in fertilization. The present study evaluates the content and distribution of anionic constituents in the oocyte-cumulus complex of rats. Polycationic colloidal gold (PCG), ruthenium red (RR) and wheat germ agglutinin (WGA) were used as cytochemical markers of anionic sites at the light (LM) and electron microscopical (EM) levels. Isolated oocyte-cumulus complexes were fixed with glutaraldehyde (GA) and OsO4 containing RR, or with GA without RR, and embedded in araldite or LR-gold. For LM, deresined, semi-thin, araldite-embedded sections were labelled with PCG intensified by silver, or with biotinylated lectins visualized by avidin-peroxidase. For EM, thin LR-gold sections were labelled with PCG, whereas RR labelling was examined in araldite sections. The zona pellucida (ZP) failed to bind any of the polycationic markers used, but intensely bound neutralized WGA. In contrast, cumulus cell membranes bound PCG but not RR, whereas the oolemma bound RR but not PCG. The results indicate that the ZP is practically devoid of negatively charged constituents, and tends to repel positively charged ligands possibly due to the presence of cationic determinants. The binding of PCG to cumulus cells probably reflects a high content of membrane-bound heparan sulphate, whereas the binding of RR to the oolema indicates the presence of membrane sialoglycoconjugates.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283161", "title": "The intramucosal distribution of gastric alcohol dehydrogenase and aldehyde dehydrogenase activity in rats.", "content": "Using qualitative and microquantitative histo-chemical techniques, alcohol dehydrogenase and aldehyde dehydrogenase activity was studied in the gastric mucosa of male and female rats. Alcohol dehydrogenase was demonstrated by staining reactions with maximum activity in surface and neck cells and with clearly weaker activity also in parietal cells. Aldehyde dehydrogenase could be detected in surface and neck cells, and also to a comparable degree in the parietal cells. Quantitative analyses of microdissected samples yielded high values for alcohol dehydrogenase activity exclusively in the superficial part of the gastric mucosa, whereas low-Km aldehyde dehydrogenase activity showed a decreasing gradient from the surface to the deeper parts of the mucosa. Sex differences could not be confirmed.", "contents": "The intramucosal distribution of gastric alcohol dehydrogenase and aldehyde dehydrogenase activity in rats. Using qualitative and microquantitative histo-chemical techniques, alcohol dehydrogenase and aldehyde dehydrogenase activity was studied in the gastric mucosa of male and female rats. Alcohol dehydrogenase was demonstrated by staining reactions with maximum activity in surface and neck cells and with clearly weaker activity also in parietal cells. Aldehyde dehydrogenase could be detected in surface and neck cells, and also to a comparable degree in the parietal cells. Quantitative analyses of microdissected samples yielded high values for alcohol dehydrogenase activity exclusively in the superficial part of the gastric mucosa, whereas low-Km aldehyde dehydrogenase activity showed a decreasing gradient from the surface to the deeper parts of the mucosa. Sex differences could not be confirmed."} {"id": "PMID:1283162", "title": "Substance P and neurokinin A immunoreactive nerve fibres in the developing salivary glands of the rat.", "content": "The time of appearance and distribution of substance P (SP) and neurokinin A (NKA) immunoreactive nerve fibres in developing salivary glands of the rat were studied by the use of indirect immunohistochemical methods. The glands were examined at daily intervals from the 15th day in utero (i.u.) until birth, and subsequently on the 2nd, 5th, 7th, 12th, 16th and 30th postnatal day. The findings were compared to samples from adult. The first SP- and NKA-immunoreactive (IR) nerve fibres appeared on the 19th day i.u. in the parotid and submandibular glands and were abundantly distributed around developing ductal branches. In the mesenchyme around the developing ductal branches of the parotid gland the fibres appeared on the 20th day i.u. In the submandibular gland NKA-IR fibres appeared in the mesenchyme surrounding the developing ductal branches on the 19th day i.u. and SP-IR fibres on the 21st day i.u. Around blood vessels of both glands, SP- and NKA-IR fibres made their appearance only much later, on the second postnatal day. The number of SP- and NKA-IR nerve fibres in the developing salivary glands was already high on the 19th day i.u. when they were first detected. From this point up to the 16th postnatal day the glands were richly innervated by the fibres, but later the numbers slowly decreased to adult levels. The abundance of SP- and NKA-IR nerve fibres especially around the ductal branches and secretory structures in the developing salivary glands suggests a role in the functional maturation of salivary glands.", "contents": "Substance P and neurokinin A immunoreactive nerve fibres in the developing salivary glands of the rat. The time of appearance and distribution of substance P (SP) and neurokinin A (NKA) immunoreactive nerve fibres in developing salivary glands of the rat were studied by the use of indirect immunohistochemical methods. The glands were examined at daily intervals from the 15th day in utero (i.u.) until birth, and subsequently on the 2nd, 5th, 7th, 12th, 16th and 30th postnatal day. The findings were compared to samples from adult. The first SP- and NKA-immunoreactive (IR) nerve fibres appeared on the 19th day i.u. in the parotid and submandibular glands and were abundantly distributed around developing ductal branches. In the mesenchyme around the developing ductal branches of the parotid gland the fibres appeared on the 20th day i.u. In the submandibular gland NKA-IR fibres appeared in the mesenchyme surrounding the developing ductal branches on the 19th day i.u. and SP-IR fibres on the 21st day i.u. Around blood vessels of both glands, SP- and NKA-IR fibres made their appearance only much later, on the second postnatal day. The number of SP- and NKA-IR nerve fibres in the developing salivary glands was already high on the 19th day i.u. when they were first detected. From this point up to the 16th postnatal day the glands were richly innervated by the fibres, but later the numbers slowly decreased to adult levels. The abundance of SP- and NKA-IR nerve fibres especially around the ductal branches and secretory structures in the developing salivary glands suggests a role in the functional maturation of salivary glands."} {"id": "PMID:1283163", "title": "Calcitonin gene-related peptide, substance P and GAP-43/B-50 immunoreactivity in the normal and arthrotic knee joint of the mouse.", "content": "The aim of this study was to describe the normal distribution of calcitonin gene-related peptide (CGRP) and substance P (SP) containing fibres in the knee joint of the mouse and to obtain insight into the changes in innervation associated with degenerative processes in the joint. Arthrosis was induced by a single subpatellar intra-articular injection of bacterial collagenase. After decalcification in EDTA solutions, the CGRP and SP fibres were visualized by peroxidase-antiperoxidase pre-embedding immunocytochemistry for light microscopy. Control experiments on the mouse brain as a reference for the effect of EDTA on the immunostaining showed that the decalcification procedure with EDTA had not impaired the immunostaining. A rich innervation of thin varicose CGRP and SP immunoreactive fibres was found in most peri- and intra-articular tissue components. The periosteum, synovial tissues, the joint capsule and the intra-articular fat tissues were richly innervated. Less intense innervations were also found in the subchondral bone plates of the tibio-femoral joint and of the patella. Fibres were also found in the soft tissues between the patellar tendon and the femoral groove. No differences could be found between the location of CGRP and SP fibres with respect to the localization in the joint, but generally more CGRP fibres were found. The collagenase-induced osteoarthrosis was characterized by sclerosis of the subchondral bone, patellar dislocation, osteophyte formation, synovial proliferation and by severe cartilage abrasion, particularly on the medial side of the femoro-tibial joint. The overall distribution of CGRP and SP fibres was the same as in the control joints. However, major differences were found in all studied joints at specific locations around the cruciate ligaments, in the synovium around the patella, in the soft tissues lateral of the patella and in plica tissue between the patella and femoral groove. The CGRP and SP innervation was no longer detectable by immunolabelling with the antibodies. With a polyclonal antibody to the growth associated protein GAP-43/B-50, signs of degenerated axonal profiles were observed in these locations. At other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal. In conclusion, the present study provides detailed information on the localization of CGRP and SP fibres, which may be involved in pain perception. Knowledge of the changes that occur during arthrosis may give more insight into the clinical symptoms.", "contents": "Calcitonin gene-related peptide, substance P and GAP-43/B-50 immunoreactivity in the normal and arthrotic knee joint of the mouse. The aim of this study was to describe the normal distribution of calcitonin gene-related peptide (CGRP) and substance P (SP) containing fibres in the knee joint of the mouse and to obtain insight into the changes in innervation associated with degenerative processes in the joint. Arthrosis was induced by a single subpatellar intra-articular injection of bacterial collagenase. After decalcification in EDTA solutions, the CGRP and SP fibres were visualized by peroxidase-antiperoxidase pre-embedding immunocytochemistry for light microscopy. Control experiments on the mouse brain as a reference for the effect of EDTA on the immunostaining showed that the decalcification procedure with EDTA had not impaired the immunostaining. A rich innervation of thin varicose CGRP and SP immunoreactive fibres was found in most peri- and intra-articular tissue components. The periosteum, synovial tissues, the joint capsule and the intra-articular fat tissues were richly innervated. Less intense innervations were also found in the subchondral bone plates of the tibio-femoral joint and of the patella. Fibres were also found in the soft tissues between the patellar tendon and the femoral groove. No differences could be found between the location of CGRP and SP fibres with respect to the localization in the joint, but generally more CGRP fibres were found. The collagenase-induced osteoarthrosis was characterized by sclerosis of the subchondral bone, patellar dislocation, osteophyte formation, synovial proliferation and by severe cartilage abrasion, particularly on the medial side of the femoro-tibial joint. The overall distribution of CGRP and SP fibres was the same as in the control joints. However, major differences were found in all studied joints at specific locations around the cruciate ligaments, in the synovium around the patella, in the soft tissues lateral of the patella and in plica tissue between the patella and femoral groove. The CGRP and SP innervation was no longer detectable by immunolabelling with the antibodies. With a polyclonal antibody to the growth associated protein GAP-43/B-50, signs of degenerated axonal profiles were observed in these locations. At other peripheral locations, such as the muscles, the GAP-43/B-50 distribution was normal. In conclusion, the present study provides detailed information on the localization of CGRP and SP fibres, which may be involved in pain perception. Knowledge of the changes that occur during arthrosis may give more insight into the clinical symptoms."} {"id": "PMID:1283164", "title": "Co-localization and molecular association of dystrophin with laminin at the surface of mouse and human myotubes.", "content": "In Duchenne muscular dystrophy (DMD), deficiency of the protein dystrophin results in necrosis of muscle myofibres, associated with lesions in the sarcolemma and surrounding basal lamina. Dystrophin has been proposed to be a major component of the sub-sarcolemmal cytoskeleton involved in maintaining the integrity of the myofibre plasma membrane, and is known to associate with a group of sarcolemmal glycoproteins, one of which exhibits high affinity binding to the basal lamina component laminin. However, a direct or indirect transmembrane association of dystrophin in muscle cells with the myofibre basal lamina has not been demonstrated. To address this question we have examined dystrophin immunostaining and immunoprecipitation patterns in cultured mouse and human myotubes in comparison with that of the basal lamina component, laminin. Dual-immunolabelling revealed virtually complete co-localization of dystrophin on the inside surface of the muscle cell sarcolemma with plaques and veined arrays of laminin accumulating on the extracellular face. This pattern of laminin and dystrophin distribution was distinct from that of other cell surface molecules expressed in myotubes such as the neural cell adhesion molecule, NCAM, and the beta 1 integrin receptor, and immunoprecipitation of dystrophin from solubilized myotube extracts resulted in co-purification of laminin B1 chain confirming an association between these two components. The results thus provide the first direct cellular evidence of a transmembrane linkage between dystrophin in the sarcolemmal cytoskeleton with laminin in the overlying basal lamina. While the immunocytochemical distribution of laminin was apparently normal in dystrophin-deficient muscle cells, elevated levels of soluble laminin were present in extracts of mdx compared with normal mouse skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Co-localization and molecular association of dystrophin with laminin at the surface of mouse and human myotubes. In Duchenne muscular dystrophy (DMD), deficiency of the protein dystrophin results in necrosis of muscle myofibres, associated with lesions in the sarcolemma and surrounding basal lamina. Dystrophin has been proposed to be a major component of the sub-sarcolemmal cytoskeleton involved in maintaining the integrity of the myofibre plasma membrane, and is known to associate with a group of sarcolemmal glycoproteins, one of which exhibits high affinity binding to the basal lamina component laminin. However, a direct or indirect transmembrane association of dystrophin in muscle cells with the myofibre basal lamina has not been demonstrated. To address this question we have examined dystrophin immunostaining and immunoprecipitation patterns in cultured mouse and human myotubes in comparison with that of the basal lamina component, laminin. Dual-immunolabelling revealed virtually complete co-localization of dystrophin on the inside surface of the muscle cell sarcolemma with plaques and veined arrays of laminin accumulating on the extracellular face. This pattern of laminin and dystrophin distribution was distinct from that of other cell surface molecules expressed in myotubes such as the neural cell adhesion molecule, NCAM, and the beta 1 integrin receptor, and immunoprecipitation of dystrophin from solubilized myotube extracts resulted in co-purification of laminin B1 chain confirming an association between these two components. The results thus provide the first direct cellular evidence of a transmembrane linkage between dystrophin in the sarcolemmal cytoskeleton with laminin in the overlying basal lamina. While the immunocytochemical distribution of laminin was apparently normal in dystrophin-deficient muscle cells, elevated levels of soluble laminin were present in extracts of mdx compared with normal mouse skeletal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283165", "title": "Localization of ahe alpha 6 and beta 4 integrin subunits in normal human non-lymphoid tissues.", "content": "The alpha 6/beta 4 integrin, of undefined receptor activity, has been shown to be expressed in a variety of murine epithelial cells. To gain information on the role of this heterodimer in tissue architecture as well as in malignant transformation we have performed an extensive immunohistochemical analysis of normal human tissues using monoclonal antibodies to alpha 6 and beta 4 subunits. Because alpha 6 is known to associate also with the beta 1 subunit to form a non-promiscuous receptor for laminin, the expression of beta 1 chain was also evaluated. The results of this study have shown that the alpha 6 chain has a wide distribution in tissues, including small vessels and peripheral nerves. alpha 6 colocalizes with beta 4 and beta 1 in most epithelial cells at the basolateral or basal aspect abutting the basement membrane. In a minority of tissues lacking beta 4, the alpha 6 chain is coexpressed with beta 1. These findings demonstrate that the expression of alpha 6/beta 1 laminin receptor and alpha 6/beta 4 heterodimer is phylogenetically conserved, suggesting that they are likely to play an important role in cellular scaffolding through binding to laminin and to still uncharacterized ligand/s present in basement membranes.", "contents": "Localization of ahe alpha 6 and beta 4 integrin subunits in normal human non-lymphoid tissues. The alpha 6/beta 4 integrin, of undefined receptor activity, has been shown to be expressed in a variety of murine epithelial cells. To gain information on the role of this heterodimer in tissue architecture as well as in malignant transformation we have performed an extensive immunohistochemical analysis of normal human tissues using monoclonal antibodies to alpha 6 and beta 4 subunits. Because alpha 6 is known to associate also with the beta 1 subunit to form a non-promiscuous receptor for laminin, the expression of beta 1 chain was also evaluated. The results of this study have shown that the alpha 6 chain has a wide distribution in tissues, including small vessels and peripheral nerves. alpha 6 colocalizes with beta 4 and beta 1 in most epithelial cells at the basolateral or basal aspect abutting the basement membrane. In a minority of tissues lacking beta 4, the alpha 6 chain is coexpressed with beta 1. These findings demonstrate that the expression of alpha 6/beta 1 laminin receptor and alpha 6/beta 4 heterodimer is phylogenetically conserved, suggesting that they are likely to play an important role in cellular scaffolding through binding to laminin and to still uncharacterized ligand/s present in basement membranes."} {"id": "PMID:1283166", "title": "A chimeric N-cadherin/beta 1-integrin receptor which localizes to both cell-cell and cell-matrix adhesions.", "content": "To study the molecular mechanisms involved in formation of cell contacts, we have transfected cultured cells with a chimeric cDNA encoding the cytoplasmic and transmembrane domains of beta 1 integrin and the extracellular region of N-cadherin and determined the subcellular distribution of the chimeric molecule. We show that the chimeric receptor associates preferentially with cell-matrix focal contacts, suggesting that its distribution is directed by its beta 1 integrin segment, presumably via interactions of the cytoplasmic domain with cytoskeletal elements characteristic of focal contacts. Transfected cells which expressed relatively high levels of the cadherin/integrin chimera underwent an apparent epithelialization and contained the molecule both in cell-matrix and cell-cell contacts. Location in cell-cell contacts indicates competence of the cadherin extracellular domain to participate in formation of cell-cell junctions using a foreign cytoplasmic domain. Labeling of these cultures for talin, which is normally associated only with matrix adhesions, revealed specific labeling along the newly formed intercellular junctions. This suggests that the local association of talin with these sites is induced by the cytoplasmic tail of beta 1 integrin receptor presented by the chimeric protein. These results suggest that the formation of adherens-type junctions is driven by the cooperative interactions of the relevant adhesion molecules (cadherins and integrins) both with the respective extracellular ligands and with the cytoskeleton.", "contents": "A chimeric N-cadherin/beta 1-integrin receptor which localizes to both cell-cell and cell-matrix adhesions. To study the molecular mechanisms involved in formation of cell contacts, we have transfected cultured cells with a chimeric cDNA encoding the cytoplasmic and transmembrane domains of beta 1 integrin and the extracellular region of N-cadherin and determined the subcellular distribution of the chimeric molecule. We show that the chimeric receptor associates preferentially with cell-matrix focal contacts, suggesting that its distribution is directed by its beta 1 integrin segment, presumably via interactions of the cytoplasmic domain with cytoskeletal elements characteristic of focal contacts. Transfected cells which expressed relatively high levels of the cadherin/integrin chimera underwent an apparent epithelialization and contained the molecule both in cell-matrix and cell-cell contacts. Location in cell-cell contacts indicates competence of the cadherin extracellular domain to participate in formation of cell-cell junctions using a foreign cytoplasmic domain. Labeling of these cultures for talin, which is normally associated only with matrix adhesions, revealed specific labeling along the newly formed intercellular junctions. This suggests that the local association of talin with these sites is induced by the cytoplasmic tail of beta 1 integrin receptor presented by the chimeric protein. These results suggest that the formation of adherens-type junctions is driven by the cooperative interactions of the relevant adhesion molecules (cadherins and integrins) both with the respective extracellular ligands and with the cytoskeleton."} {"id": "PMID:1283167", "title": "Behavior of large nucleic acids in reversed-phase high-performance liquid chromatography.", "content": "Large nucleic acids can be separated by reversed-phase high-performance liquid chromatography. Analysis shows that the retention time depends not only on the chain length but also on the base composition and the secondary structure of the molecule. A model is proposed to interpret their behavior. This model, called \"multiple-point interaction theory\" is based on the observation that macromolecules are flexible and very large compared to the hydrophobic phase (octadecylsilane) of the column. It explains the behavior of large nucleic acids in terms of an equilibrium of the macromolecule between the two phases through a multiple-point attachment to the chromatographic matrix, the parameters of the equilibrium being both the hydrophobicity of the base and the number of attachment points. This model fits the experimental data and can be applied to all types of flexible macromolecules, especially proteins and nucleic acids, when they are chromatographed on reversed-phase columns. The model is used to explain the separation of nucleic acids of importance in molecular biology.", "contents": "Behavior of large nucleic acids in reversed-phase high-performance liquid chromatography. Large nucleic acids can be separated by reversed-phase high-performance liquid chromatography. Analysis shows that the retention time depends not only on the chain length but also on the base composition and the secondary structure of the molecule. A model is proposed to interpret their behavior. This model, called \"multiple-point interaction theory\" is based on the observation that macromolecules are flexible and very large compared to the hydrophobic phase (octadecylsilane) of the column. It explains the behavior of large nucleic acids in terms of an equilibrium of the macromolecule between the two phases through a multiple-point attachment to the chromatographic matrix, the parameters of the equilibrium being both the hydrophobicity of the base and the number of attachment points. This model fits the experimental data and can be applied to all types of flexible macromolecules, especially proteins and nucleic acids, when they are chromatographed on reversed-phase columns. The model is used to explain the separation of nucleic acids of importance in molecular biology."} {"id": "PMID:1283168", "title": "Rapid breakthrough measurement of void volume for field-flow fractionation channels.", "content": "A peak breakthrough technique is described and evaluated for measuring the void volume of field-flow fractionation (FFF) channels, particularly those used for flow FFF. This technique uses a high-molecular-mass macromolecular or particulate probe that can be displaced rapidly by flow through the FFF channel with minimal transverse diffusion. The particles that emerge first are those carried through the entire length near the channel centerline at the apex of the parabolic flow profile. These particles generate a sharp breakthrough profile. The measured breakthrough time is two thirds of the void time, thus making it possible to calculate both the void time and the associated void volume. This method, although applicable to all FFF channels (and capable of extension to open tubes), is particularly useful for flow FFF because conventional low-molecular-mass void probes can diffuse into the permeable walls and thus distort void measurements. The theoretical basis of the breakthrough technique and an explanation for the sharpness of the breakthrough front are given. A method for compensating for deviations from perfect sharpness is developed in which the breakthrough time is identified with the time needed to reach 85-88% of the breakthrough peak maximum. Preliminary experimental results are shown using various protein probes in four different FFF channel systems.", "contents": "Rapid breakthrough measurement of void volume for field-flow fractionation channels. A peak breakthrough technique is described and evaluated for measuring the void volume of field-flow fractionation (FFF) channels, particularly those used for flow FFF. This technique uses a high-molecular-mass macromolecular or particulate probe that can be displaced rapidly by flow through the FFF channel with minimal transverse diffusion. The particles that emerge first are those carried through the entire length near the channel centerline at the apex of the parabolic flow profile. These particles generate a sharp breakthrough profile. The measured breakthrough time is two thirds of the void time, thus making it possible to calculate both the void time and the associated void volume. This method, although applicable to all FFF channels (and capable of extension to open tubes), is particularly useful for flow FFF because conventional low-molecular-mass void probes can diffuse into the permeable walls and thus distort void measurements. The theoretical basis of the breakthrough technique and an explanation for the sharpness of the breakthrough front are given. A method for compensating for deviations from perfect sharpness is developed in which the breakthrough time is identified with the time needed to reach 85-88% of the breakthrough peak maximum. Preliminary experimental results are shown using various protein probes in four different FFF channel systems."} {"id": "PMID:1283169", "title": "Treatment of elective mute behavior in two developmentally delayed children using modeling and contingency management.", "content": "Most classification schemes differentiate elective mutism from language problems seen in the developmentally delayed population. Two preschool developmentally delayed children were treated for speech reluctance using modeling and contingency management. Employing a multiple baseline across therapists, it was found that these treatment components were effective in increasing frequency of labeling behavior in both children. Results were maintained at follow-up. Generalization to new words and to spontaneous speech were also noted, and suggest that characteristics of elective mutism in this population may be similar to what is found in the general population.", "contents": "Treatment of elective mute behavior in two developmentally delayed children using modeling and contingency management. Most classification schemes differentiate elective mutism from language problems seen in the developmentally delayed population. Two preschool developmentally delayed children were treated for speech reluctance using modeling and contingency management. Employing a multiple baseline across therapists, it was found that these treatment components were effective in increasing frequency of labeling behavior in both children. Results were maintained at follow-up. Generalization to new words and to spontaneous speech were also noted, and suggest that characteristics of elective mutism in this population may be similar to what is found in the general population."} {"id": "PMID:1283170", "title": "Chordoma involving the skin: an immunohistochemical study of 11 cases.", "content": "Immunohistochemical properties were studied in 16 lesions from 11 patients with chordoma involving the skin. There were nine men and two women ranging from 21 to 62 years old (mean, 42.6). The initial tumor was sacrococcygeal in 10 cases and nasopharyngeal in 1 case. Three lesions represented a direct extension from the primary tumor to the skin, and 13 lesions were examples of local recurrences in the skin. Immunohistochemically, all lesions showed positivity for keratin, whereas 14 lesions were positive for vimentin and 12 for protein S-100. Epithelial membrane antigen was positive in four instances and carcinoembryonic antigen was negative in all studies. No significant difference was observed between the immunoprofile of cases of direct extension and those of local recurrences. Overall, the remarkable triple positivity for keratin, vimentin, and protein S-100 was observed in 11 lesions from eight different cases (73%). This study confirmed the utility of immunohistochemistry in the differential diagnosis of chordoma from tumors with similar histologic characteristics encountered in the skin.", "contents": "Chordoma involving the skin: an immunohistochemical study of 11 cases. Immunohistochemical properties were studied in 16 lesions from 11 patients with chordoma involving the skin. There were nine men and two women ranging from 21 to 62 years old (mean, 42.6). The initial tumor was sacrococcygeal in 10 cases and nasopharyngeal in 1 case. Three lesions represented a direct extension from the primary tumor to the skin, and 13 lesions were examples of local recurrences in the skin. Immunohistochemically, all lesions showed positivity for keratin, whereas 14 lesions were positive for vimentin and 12 for protein S-100. Epithelial membrane antigen was positive in four instances and carcinoembryonic antigen was negative in all studies. No significant difference was observed between the immunoprofile of cases of direct extension and those of local recurrences. Overall, the remarkable triple positivity for keratin, vimentin, and protein S-100 was observed in 11 lesions from eight different cases (73%). This study confirmed the utility of immunohistochemistry in the differential diagnosis of chordoma from tumors with similar histologic characteristics encountered in the skin."} {"id": "PMID:1283171", "title": "Keratin expression in normal skin and epidermal neoplasms demonstrated by a panel of monoclonal antibodies.", "content": "The tissue labelling of a panel of monoclonal antikeratin antibodies (LL001, LL002, LL003, LP2K, BA17, LP34, CAM5.2, and LH1) recognising keratins 1, 5, 8, 10, 14, 18, and 19 were investigated in frozen and formalin-fixed normal skin. Antibodies LL001, LL003, BA17, LP34, CAM5.2, and LH1 were found to be reactive in formalin-fixed material and were used to study 23 basal cell carcinomas, 8 squamous cell carcinomas, 5 keratoacanthomas, 5 Bowen's disease, and 6 clear cell acanthomas. All these tumours demonstrated a loss of keratin 10 expression as demonstrated by loss of labelling with LH1. Keratin 14 expression, as demonstrated by LL001, was reduced but present in all the tumours except squamous cell carcinomas and keratoacanthomas where increased labelling was observed in the more differentiated areas of these tumours. Simple epithelial keratin expression was demonstrated by positive labelling with CAM5.2 and keratin 19 by BA17 in a third of basal cell carcinomas and squamous cell carcinomas. Three of the five keratoacanthomas labelled with BA17, indicating the presence of keratin 19 in these lesions. These results support the concept that keratin expression is a phenotypic marker of the state of differentiation or malignant transformation and that patterns of keratin expression are not specific to any particular premalignant or malignant disorder.", "contents": "Keratin expression in normal skin and epidermal neoplasms demonstrated by a panel of monoclonal antibodies. The tissue labelling of a panel of monoclonal antikeratin antibodies (LL001, LL002, LL003, LP2K, BA17, LP34, CAM5.2, and LH1) recognising keratins 1, 5, 8, 10, 14, 18, and 19 were investigated in frozen and formalin-fixed normal skin. Antibodies LL001, LL003, BA17, LP34, CAM5.2, and LH1 were found to be reactive in formalin-fixed material and were used to study 23 basal cell carcinomas, 8 squamous cell carcinomas, 5 keratoacanthomas, 5 Bowen's disease, and 6 clear cell acanthomas. All these tumours demonstrated a loss of keratin 10 expression as demonstrated by loss of labelling with LH1. Keratin 14 expression, as demonstrated by LL001, was reduced but present in all the tumours except squamous cell carcinomas and keratoacanthomas where increased labelling was observed in the more differentiated areas of these tumours. Simple epithelial keratin expression was demonstrated by positive labelling with CAM5.2 and keratin 19 by BA17 in a third of basal cell carcinomas and squamous cell carcinomas. Three of the five keratoacanthomas labelled with BA17, indicating the presence of keratin 19 in these lesions. These results support the concept that keratin expression is a phenotypic marker of the state of differentiation or malignant transformation and that patterns of keratin expression are not specific to any particular premalignant or malignant disorder."} {"id": "PMID:1283172", "title": "Benign lymphangioendothelioma: report of 2 cases.", "content": "Benign lymphangioendothelioma is an acquired vascular proliferation clinically appearing as well-demarcated, pink to red-brown macules or plaques. Histologically, numerous endothelial-lined channels are found infiltrating throughout the dermis. Recognition and differentiation from malignant vascular tumors is essential. We report 2 cases of benign lymphangioendothelioma. One of these lesions is unique in its presentation as a subcutaneous nodule. The other is also unusual, as it resolved spontaneously.", "contents": "Benign lymphangioendothelioma: report of 2 cases. Benign lymphangioendothelioma is an acquired vascular proliferation clinically appearing as well-demarcated, pink to red-brown macules or plaques. Histologically, numerous endothelial-lined channels are found infiltrating throughout the dermis. Recognition and differentiation from malignant vascular tumors is essential. We report 2 cases of benign lymphangioendothelioma. One of these lesions is unique in its presentation as a subcutaneous nodule. The other is also unusual, as it resolved spontaneously."} {"id": "PMID:1283174", "title": "T cell mapping of one epitope from thyroglobulin inducing experimental autoimmune thyroiditis (EAT).", "content": "These data collect the advance made in the last few years in our laboratory in defining one epitope from the thyroglobulin (Tg) molecule (660 KDa) inducing Experimental Autoimmune thyroiditis (EAT) in CBA/J mice. We achieved the characterization of one EAT-inducer Tg peptide by combining \"in vitro\" biochemical and immunological approaches and \"in vivo\" studies. Since T cells recognize degraded forms of the antigen and since endogenous antigens preferentially activate class I-restricted T cells, we hypothesized that one cytotoxic T cell hybridoma, named HTC2, which prevents further EAT induction in mice injected with Tg would be specific for one EAT inducer peptide. In order to identify one Tg epitope inducing EAT, enzymatic treatment of the protein by trypsin, HPLC purification and sequence analysis were performed. Simultaneously, tryptic digests were used to pulse CBA/J macrophages and tested for their ability to be recognized by HTC2 cells. Lastly, when digests were recognized by HTC2 cells their capacity to induce EAT in CBA/J mice was evaluated. To further assess the pathogenicity of the sequenced Tg peptide, one synthetic peptide was made and its capacity to induce EAT verified. By this procedure we identified for the first time one 40 amino-acid peptide from human thyroglobulin inducing EAT in CBA/J mice.", "contents": "T cell mapping of one epitope from thyroglobulin inducing experimental autoimmune thyroiditis (EAT). These data collect the advance made in the last few years in our laboratory in defining one epitope from the thyroglobulin (Tg) molecule (660 KDa) inducing Experimental Autoimmune thyroiditis (EAT) in CBA/J mice. We achieved the characterization of one EAT-inducer Tg peptide by combining \"in vitro\" biochemical and immunological approaches and \"in vivo\" studies. Since T cells recognize degraded forms of the antigen and since endogenous antigens preferentially activate class I-restricted T cells, we hypothesized that one cytotoxic T cell hybridoma, named HTC2, which prevents further EAT induction in mice injected with Tg would be specific for one EAT inducer peptide. In order to identify one Tg epitope inducing EAT, enzymatic treatment of the protein by trypsin, HPLC purification and sequence analysis were performed. Simultaneously, tryptic digests were used to pulse CBA/J macrophages and tested for their ability to be recognized by HTC2 cells. Lastly, when digests were recognized by HTC2 cells their capacity to induce EAT in CBA/J mice was evaluated. To further assess the pathogenicity of the sequenced Tg peptide, one synthetic peptide was made and its capacity to induce EAT verified. By this procedure we identified for the first time one 40 amino-acid peptide from human thyroglobulin inducing EAT in CBA/J mice."} {"id": "PMID:1283175", "title": "Molecular basis for the autoreactivity against thyroid stimulating hormone receptor.", "content": "The present report identifies an important immunogenic region of the TSH receptor and determinants on the TSH receptor for the two types of autoantibodies seen in hyperthyroid Graves' disease and hypothyroid idiopathic myxedema, TSAbs and TSBAbs, respectively. The immunogenic domain with no important functional determinants, is contained within residues 303-382 and involves residues 352-366 in particular. There are determinants flanking the immunogenic domain on the C-terminal portion of the receptor which are the TSBAb and high affinity TSH binding sites: residues 295-306, 387-395, and tyrosine 385. Determinants on the N-terminal portion of the external domain, centered on residues 38-45, are TSAb interactions linked to low affinity TSH binding important for signal generation: threonine 40 and residues 30-33, 34-37, 42-45, 52-56, and 58-61. These determinants are conserved in human and rat receptors, are not present in gonadotropin receptors, and are each related to separate actions of TSH: binding vs. signal generation. They can, therefore, account for organ specific autoimmunity and the different disease expression effected by TSBAbs vs TSAbs, i.e. hypo- vs. hyperthyroidism, respectively. It is proposed that, in the thyroid, hormonal (TSH, insulin, hydrocortisone, IGF-I) suppression of class I genes might be one means of preserving self-tolerance in the face of the hormone action to increase the expression of tissue specific genes such as thyroglobulin and thyroid peroxidase. Inappropriately high class I expression in the thyroid, i.e. if induced by interferon, viruses, or some as yet unknown agent, would contribute to the generation of autoimmune disease. Thus, it would result in increased antigen presentation to the immune system, particularly those autoantigens increased by TSH and its cAMP signal such as thyroglobulin or thyroid peroxidase, or whose turnover is increased by TSH and its cAMP signal, such as the TSH receptor. In the case of the latter, peptide 352-366, known to be near a protease sensitive site on the receptor [41,49], would now act as a potent self-antigen and induce the formation of receptor autoantibodies. It is further proposed that methimazole and high doses of iodide are therapeutically effective agents in thyroid autoimmune disease because they, in part, decrease MHC class I gene expression. Speculation is presented which suggests that elimination of negative regulation of MHC class I and the TSH receptor is an important factor in the development of autoimmune thyroid disease.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Molecular basis for the autoreactivity against thyroid stimulating hormone receptor. The present report identifies an important immunogenic region of the TSH receptor and determinants on the TSH receptor for the two types of autoantibodies seen in hyperthyroid Graves' disease and hypothyroid idiopathic myxedema, TSAbs and TSBAbs, respectively. The immunogenic domain with no important functional determinants, is contained within residues 303-382 and involves residues 352-366 in particular. There are determinants flanking the immunogenic domain on the C-terminal portion of the receptor which are the TSBAb and high affinity TSH binding sites: residues 295-306, 387-395, and tyrosine 385. Determinants on the N-terminal portion of the external domain, centered on residues 38-45, are TSAb interactions linked to low affinity TSH binding important for signal generation: threonine 40 and residues 30-33, 34-37, 42-45, 52-56, and 58-61. These determinants are conserved in human and rat receptors, are not present in gonadotropin receptors, and are each related to separate actions of TSH: binding vs. signal generation. They can, therefore, account for organ specific autoimmunity and the different disease expression effected by TSBAbs vs TSAbs, i.e. hypo- vs. hyperthyroidism, respectively. It is proposed that, in the thyroid, hormonal (TSH, insulin, hydrocortisone, IGF-I) suppression of class I genes might be one means of preserving self-tolerance in the face of the hormone action to increase the expression of tissue specific genes such as thyroglobulin and thyroid peroxidase. Inappropriately high class I expression in the thyroid, i.e. if induced by interferon, viruses, or some as yet unknown agent, would contribute to the generation of autoimmune disease. Thus, it would result in increased antigen presentation to the immune system, particularly those autoantigens increased by TSH and its cAMP signal such as thyroglobulin or thyroid peroxidase, or whose turnover is increased by TSH and its cAMP signal, such as the TSH receptor. In the case of the latter, peptide 352-366, known to be near a protease sensitive site on the receptor [41,49], would now act as a potent self-antigen and induce the formation of receptor autoantibodies. It is further proposed that methimazole and high doses of iodide are therapeutically effective agents in thyroid autoimmune disease because they, in part, decrease MHC class I gene expression. Speculation is presented which suggests that elimination of negative regulation of MHC class I and the TSH receptor is an important factor in the development of autoimmune thyroid disease.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1283177", "title": "Human chorionic gonadotrophin and subunit composition of maternal serum and coelomic and amniotic fluids in the first trimester of pregnancy.", "content": "Sixteen matched samples of first trimester amniotic fluid (AF), extraembryonic coelomic fluid (EECF) and maternal serum (MS) were assayed for intact human chorionic gonadotrophin (hCG) and free subunits. Total beta-hCG (free beta-subunit and intact hCG) levels in the EECF (median 410 kIU/l) were 61 times greater than levels in AF (median 6.73 kIU/l) and 2.8 times greater than in MS (median 141.5 kIU/l). Levels of intact hCG in the EECF (median 245 kIU/l) were 142 times greater than in AF (median 1.73 kIU/l) and 1.6 times greater than in MS (median 157 kIU/l). Free alpha-subunit levels in EECF (median 17.3 mg/l) were 66 times greater than in AF (median 0.262 mg/l) and 12 times greater than in MS (median 1.3 mg/l). Virtually all of the total beta-hCG immunoreactivity in MS can be attributed to intact hCG, but only 60% of total beta-hCG in the EECF and 20% of that in AF can be accounted for by the intact hormone. In both EECF and AF the free alpha-subunit was a major constituent; on a molar basis the ratio of free alpha:free beta:intact hCG was 1:1.2:0.3 in AF, 1:0.6:0.5 in EECF and 1:0:5 in MS. Chromatography of MS, EECF and AF on Sephadex G-100 confirmed the hCG and subunit composition of the fluids. On the basis of these findings it seems likely that previous studies showing very high levels of hCG in AF during the first trimester may have incorrectly sampled the EECF. In reality, the levels of total hCG (and free subunits) are low in the AF, and only 20% is intact hCG.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Human chorionic gonadotrophin and subunit composition of maternal serum and coelomic and amniotic fluids in the first trimester of pregnancy. Sixteen matched samples of first trimester amniotic fluid (AF), extraembryonic coelomic fluid (EECF) and maternal serum (MS) were assayed for intact human chorionic gonadotrophin (hCG) and free subunits. Total beta-hCG (free beta-subunit and intact hCG) levels in the EECF (median 410 kIU/l) were 61 times greater than levels in AF (median 6.73 kIU/l) and 2.8 times greater than in MS (median 141.5 kIU/l). Levels of intact hCG in the EECF (median 245 kIU/l) were 142 times greater than in AF (median 1.73 kIU/l) and 1.6 times greater than in MS (median 157 kIU/l). Free alpha-subunit levels in EECF (median 17.3 mg/l) were 66 times greater than in AF (median 0.262 mg/l) and 12 times greater than in MS (median 1.3 mg/l). Virtually all of the total beta-hCG immunoreactivity in MS can be attributed to intact hCG, but only 60% of total beta-hCG in the EECF and 20% of that in AF can be accounted for by the intact hormone. In both EECF and AF the free alpha-subunit was a major constituent; on a molar basis the ratio of free alpha:free beta:intact hCG was 1:1.2:0.3 in AF, 1:0.6:0.5 in EECF and 1:0:5 in MS. Chromatography of MS, EECF and AF on Sephadex G-100 confirmed the hCG and subunit composition of the fluids. On the basis of these findings it seems likely that previous studies showing very high levels of hCG in AF during the first trimester may have incorrectly sampled the EECF. In reality, the levels of total hCG (and free subunits) are low in the AF, and only 20% is intact hCG.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283178", "title": "Evidence for lipopolysaccharide binding in human granulosa-luteal cells.", "content": "We investigated whether human granulosa-luteal (GL) cells exhibited lipopolysaccharide (LPS)-binding protein, and the response of follicular aspirate cells to LPS in vitro. Follicular aspirates taken from a human in-vitro fertilization and gamete intra-fallopian-tube transfer programme were subjected to Percoll gradients in order to isolate an enriched population of GL cells. GL cells exhibited specific LPS-binding protein, detected by autoradiography of the cellular lysate on SDS-PAGE after the cells were specifically labelled with a radioiodinated, photoactivable and reducible LPS derivative. LPS binding to the cells was also detected by the appearance of immunofluorescence associated with the cellular membrane when incubated with a fluorescent conjugated LPS receptor antibody. Ninety-four per cent of the cells exhibiting immunofluorescent LPS-binding protein were also positive for the steroidogenic enzyme 3 beta-hydroxysteroid dehydrogenase, as detected by cytochemistry. In order to detect a response to LPS, the enriched population of GL cells were cultured in vitro in the presence or absence of LPS; after 16 h of culture, tumour necrosis factor-alpha (TNF) mRNA was detected by reverse transcription-polymerase chain reaction and Southern blot analysis of the amplified cDNA. The expression of TNF mRNA was enhanced when the cells were cultured in the presence of LPS, which also significantly enhanced TNF secretion into the media during the 16-h period. These results reveal that GL cells exhibit LPS-binding protein and thus increased TNF secretion occurs in response to LPS in follicular aspirate cells. The source of ovarian TNF may be leukocytes, macrophages and/or GL cells.", "contents": "Evidence for lipopolysaccharide binding in human granulosa-luteal cells. We investigated whether human granulosa-luteal (GL) cells exhibited lipopolysaccharide (LPS)-binding protein, and the response of follicular aspirate cells to LPS in vitro. Follicular aspirates taken from a human in-vitro fertilization and gamete intra-fallopian-tube transfer programme were subjected to Percoll gradients in order to isolate an enriched population of GL cells. GL cells exhibited specific LPS-binding protein, detected by autoradiography of the cellular lysate on SDS-PAGE after the cells were specifically labelled with a radioiodinated, photoactivable and reducible LPS derivative. LPS binding to the cells was also detected by the appearance of immunofluorescence associated with the cellular membrane when incubated with a fluorescent conjugated LPS receptor antibody. Ninety-four per cent of the cells exhibiting immunofluorescent LPS-binding protein were also positive for the steroidogenic enzyme 3 beta-hydroxysteroid dehydrogenase, as detected by cytochemistry. In order to detect a response to LPS, the enriched population of GL cells were cultured in vitro in the presence or absence of LPS; after 16 h of culture, tumour necrosis factor-alpha (TNF) mRNA was detected by reverse transcription-polymerase chain reaction and Southern blot analysis of the amplified cDNA. The expression of TNF mRNA was enhanced when the cells were cultured in the presence of LPS, which also significantly enhanced TNF secretion into the media during the 16-h period. These results reveal that GL cells exhibit LPS-binding protein and thus increased TNF secretion occurs in response to LPS in follicular aspirate cells. The source of ovarian TNF may be leukocytes, macrophages and/or GL cells."} {"id": "PMID:1283179", "title": "[The anti-arrhythmic efficacy of sodium valproate].", "content": "The antiarrhythmic efficacy of the anticonvulsant sodium valproate was studied in 22 patients with ventricular premature contraction in the immediate (10-15 days) and late (2-5 months) periods of therapy. The prolong antiarrhythmic effect of the drug was observed in 66% of the patients in whom it was beneficial in the first days of therapy. The results obtained provide strong evidence for the efficacy of sodium valproate in patients with ventricular premature contraction occurring in the presence of neurocirculatory dystonia.", "contents": "[The anti-arrhythmic efficacy of sodium valproate]. The antiarrhythmic efficacy of the anticonvulsant sodium valproate was studied in 22 patients with ventricular premature contraction in the immediate (10-15 days) and late (2-5 months) periods of therapy. The prolong antiarrhythmic effect of the drug was observed in 66% of the patients in whom it was beneficial in the first days of therapy. The results obtained provide strong evidence for the efficacy of sodium valproate in patients with ventricular premature contraction occurring in the presence of neurocirculatory dystonia."} {"id": "PMID:1283180", "title": "[The clinico-hemodynamic effects of the activator of the GABA-ergic stress-limiting system sodium valproate (acediprol) and etatsizin in patients with cardiac arrhythmias].", "content": "Hemodynamic and antiarrhythmic effects of acediprol and ethacizine were examined in 51 patients with premature ventricular contraction concurrent with neurocirculatory dystonia and coronary heart disease. It was ascertained that acediprol exerted a positive inotropic action and ethacizine lowered myocardial contractility. Acediprol therapy prevents or attenuates the hypokinetic and arrhythmogenic effects of stimulated stress in patients with ischemic and non-ischemic arrhythmias. The preventive antiarrhythmic effect of acediprol is the most pronounced in patients with neurocirculatory dystonia. Ethacizine fails to improve hemodynamic supply of the stress test and enhances stress-related hypodynamia in some patients.", "contents": "[The clinico-hemodynamic effects of the activator of the GABA-ergic stress-limiting system sodium valproate (acediprol) and etatsizin in patients with cardiac arrhythmias]. Hemodynamic and antiarrhythmic effects of acediprol and ethacizine were examined in 51 patients with premature ventricular contraction concurrent with neurocirculatory dystonia and coronary heart disease. It was ascertained that acediprol exerted a positive inotropic action and ethacizine lowered myocardial contractility. Acediprol therapy prevents or attenuates the hypokinetic and arrhythmogenic effects of stimulated stress in patients with ischemic and non-ischemic arrhythmias. The preventive antiarrhythmic effect of acediprol is the most pronounced in patients with neurocirculatory dystonia. Ethacizine fails to improve hemodynamic supply of the stress test and enhances stress-related hypodynamia in some patients."} {"id": "PMID:1283182", "title": "Antihypertensive therapy: new strategies beyond blood pressure control.", "content": "Mild-to-moderate essential hypertension is the most common medical problem seen by physicians in Western populations, and pharmacologic antihypertensive therapy is now usually undertaken. Clinical trials have shown that lowering of elevated blood pressure using diuretics and beta-blockers reduces cardiovascular morbidity and mortality. Despite these benefits, the trials have provided no convincing evidence that the incidence of coronary artery disease or its complications is reduced: Treated hypertensive patients remain at increased cardiovascular risk compared with untreated normotensive subjects. Possible explanations for this disappointing outcome are that the drugs used may themselves have negative effects on serum lipids, glucose, and insulin resistance, thereby outweighing their antihypertensive benefits. An equally important role in this respect may be played by the diseases and therapies most commonly found in association with mild-to-moderate hypertension: hyperlipidemia, type II diabetes, coronary artery disease, left ventricular hypertrophy, cardiac arrhythmias, peripheral arterial disease, and nephropathy. Such conditions may be potent determinants of what constitutes the optimal first-line choice of antihypertensive therapy. Furthermore, the negative effects that antihypertensive drugs can have on quality-of-life factors may result in noncompliance and ineffective long-term treatment. Therefore, in a new therapeutic approach to the treatment of high blood pressure, it would be logical to base antihypertensive therapy on strategies that not only lower the blood pressure but that have beneficial impacts on hemodynamics, vascular and cardiac structure, metabolism, and quality-of-life issues.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Antihypertensive therapy: new strategies beyond blood pressure control. Mild-to-moderate essential hypertension is the most common medical problem seen by physicians in Western populations, and pharmacologic antihypertensive therapy is now usually undertaken. Clinical trials have shown that lowering of elevated blood pressure using diuretics and beta-blockers reduces cardiovascular morbidity and mortality. Despite these benefits, the trials have provided no convincing evidence that the incidence of coronary artery disease or its complications is reduced: Treated hypertensive patients remain at increased cardiovascular risk compared with untreated normotensive subjects. Possible explanations for this disappointing outcome are that the drugs used may themselves have negative effects on serum lipids, glucose, and insulin resistance, thereby outweighing their antihypertensive benefits. An equally important role in this respect may be played by the diseases and therapies most commonly found in association with mild-to-moderate hypertension: hyperlipidemia, type II diabetes, coronary artery disease, left ventricular hypertrophy, cardiac arrhythmias, peripheral arterial disease, and nephropathy. Such conditions may be potent determinants of what constitutes the optimal first-line choice of antihypertensive therapy. Furthermore, the negative effects that antihypertensive drugs can have on quality-of-life factors may result in noncompliance and ineffective long-term treatment. Therefore, in a new therapeutic approach to the treatment of high blood pressure, it would be logical to base antihypertensive therapy on strategies that not only lower the blood pressure but that have beneficial impacts on hemodynamics, vascular and cardiac structure, metabolism, and quality-of-life issues.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283184", "title": "Pharmacodynamics of nilvadipine, a new dihydropyridine-type calcium antagonist.", "content": "Nilvadipine is a new calcium antagonist of the dihydropyridine type. It reduces blood pressure by high-affinity blockade of calcium channels in arterial cells, which leads to relaxation of arterial vessels. Nilvadipine has both pharmacokinetic and pharmacodynamic advantages compared to nifedipine (the prototype of the dihydropyridines). The duration of action is longer and it has a 4- to 16-fold higher vasodilatory potency that is accompanied by less cardiodepression and adrenergic counterregulation. The higher vascular selectivity of nilvadipine is documented by its vascular/cardiac potency ratio of 251, which is 9- to 10-fold greater than that of nifedipine. When used therapeutically as an antihypertensive agent, even in patients with heart failure or concomitant beta-blockade, nilvadipine has no negative inotropic, chronotropic, or dromotropic effects. Nilvadipine has been shown to have a more potent antiatherogenic effect than that of nifedipine in vitro and in animal models.", "contents": "Pharmacodynamics of nilvadipine, a new dihydropyridine-type calcium antagonist. Nilvadipine is a new calcium antagonist of the dihydropyridine type. It reduces blood pressure by high-affinity blockade of calcium channels in arterial cells, which leads to relaxation of arterial vessels. Nilvadipine has both pharmacokinetic and pharmacodynamic advantages compared to nifedipine (the prototype of the dihydropyridines). The duration of action is longer and it has a 4- to 16-fold higher vasodilatory potency that is accompanied by less cardiodepression and adrenergic counterregulation. The higher vascular selectivity of nilvadipine is documented by its vascular/cardiac potency ratio of 251, which is 9- to 10-fold greater than that of nifedipine. When used therapeutically as an antihypertensive agent, even in patients with heart failure or concomitant beta-blockade, nilvadipine has no negative inotropic, chronotropic, or dromotropic effects. Nilvadipine has been shown to have a more potent antiatherogenic effect than that of nifedipine in vitro and in animal models."} {"id": "PMID:1283185", "title": "Pharmacokinetics of nilvadipine.", "content": "Nilvadipine is absorbed rapidly and completely and its absolute bioavailability is about 14-19% because of its high first-pass metabolism. Maximum plasma levels and the extent of bioavailability increase proportionally with the dose. Nilvadipine is mainly excreted via the kidney as inactive metabolites. Slow tissue redistribution is probably the reason for the terminal elimination half-life of 15-20 h. There was a good correlation between the estimated tissue concentration and the reduction in blood pressure in patients. The use of the sustained-release pellet formulation can prevent plasma level peaks and thereby lessen the typical side effects of dihydropyridine calcium antagonists. The pharmacokinetics of nilvadipine were not affected by impaired renal function, and although the bioavailability was increased in liver cirrhosis, there was no accumulation after repeated doses. There was no effect on plasma digoxin levels. The plasma concentration of nilvadipine can be affected by either activation or inhibition of the cytochrome P450 system. The use of a sustained-release once-a-day formulation to lower the peaks in plasma levels along with nilvadipine's long terminal half-life means that this well-tolerated pharmaceutical formulation can be employed in clinical trials for the treatment of hypertension and expected to work over 24 h.", "contents": "Pharmacokinetics of nilvadipine. Nilvadipine is absorbed rapidly and completely and its absolute bioavailability is about 14-19% because of its high first-pass metabolism. Maximum plasma levels and the extent of bioavailability increase proportionally with the dose. Nilvadipine is mainly excreted via the kidney as inactive metabolites. Slow tissue redistribution is probably the reason for the terminal elimination half-life of 15-20 h. There was a good correlation between the estimated tissue concentration and the reduction in blood pressure in patients. The use of the sustained-release pellet formulation can prevent plasma level peaks and thereby lessen the typical side effects of dihydropyridine calcium antagonists. The pharmacokinetics of nilvadipine were not affected by impaired renal function, and although the bioavailability was increased in liver cirrhosis, there was no accumulation after repeated doses. There was no effect on plasma digoxin levels. The plasma concentration of nilvadipine can be affected by either activation or inhibition of the cytochrome P450 system. The use of a sustained-release once-a-day formulation to lower the peaks in plasma levels along with nilvadipine's long terminal half-life means that this well-tolerated pharmaceutical formulation can be employed in clinical trials for the treatment of hypertension and expected to work over 24 h."} {"id": "PMID:1283186", "title": "Compliance and the benefit/risk relationship of antihypertensive treatment.", "content": "Compliance is defined as a patient's behavior in terms of taking prescribed medication, following diets, or executing medically recommended lifestyle changes. Furthermore, compliance measures the extent to which a person's behavior coincides with medical or health advice. The measurement of compliance over time is still a problem. The recently developed medication monitors, however, enable precise documentation of the taking of pills out of the container over long time periods. Long-term compliance with antihypertensive treatments is, referring to the literature, about 50%. The causes of partial compliance are not yet well known. Partial compliance is often accompanied by reduced benefit, e.g., poor blood pressure control. There are even strong arguments that partial compliance increases the risks of treatment, especially with beta-blockers. Thus, the traditional physicians' nonperception of patients' partial compliance is no longer acceptable, as partial compliance has a negative impact on the benefit/risk ratio.", "contents": "Compliance and the benefit/risk relationship of antihypertensive treatment. Compliance is defined as a patient's behavior in terms of taking prescribed medication, following diets, or executing medically recommended lifestyle changes. Furthermore, compliance measures the extent to which a person's behavior coincides with medical or health advice. The measurement of compliance over time is still a problem. The recently developed medication monitors, however, enable precise documentation of the taking of pills out of the container over long time periods. Long-term compliance with antihypertensive treatments is, referring to the literature, about 50%. The causes of partial compliance are not yet well known. Partial compliance is often accompanied by reduced benefit, e.g., poor blood pressure control. There are even strong arguments that partial compliance increases the risks of treatment, especially with beta-blockers. Thus, the traditional physicians' nonperception of patients' partial compliance is no longer acceptable, as partial compliance has a negative impact on the benefit/risk ratio."} {"id": "PMID:1283187", "title": "24-hour blood pressure control after single daily doses of nivaldipine in patients with essential hypertension.", "content": "In an open monocentric phase II study, 20 inpatients with hypertension were treated with a single daily dose of nilvadipine for 3 weeks after a 1-week placebo washout phase. The initial dose in all patients was 8 mg/day p.o.; this was doubled to 16 mg once daily if an adequate blood pressure reduction was not achieved after 10 days on 8 mg. The objective of the study was to investigate the effect of this new calcium antagonist on the blood pressure in hypertensive patients. This was done by means of a 24-h blood pressure profile (with measurements at 0.5, 1, 2, 4, 8, 12, and 24 h after administration), and over the complete course of the treatment period (blood pressure measurements each day just before the medication was given). In addition, by determination of the nilvadipine plasma levels on the first, tenth, and last medication day, a possible concentration-efficacy relationship was to be ascertained between plasma concentration of nilvadipine and the observed blood pressure-lowering effect of the drug. Adequate blood pressure reductions were achieved with nilvadipine 8 mg once daily in 13 patients; 7 required a doubling of the dosage to 16 mg/day. Already on the first day of therapy, both the systolic and diastolic blood pressures were significantly reduced compared to those in the placebo phase (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "24-hour blood pressure control after single daily doses of nivaldipine in patients with essential hypertension. In an open monocentric phase II study, 20 inpatients with hypertension were treated with a single daily dose of nilvadipine for 3 weeks after a 1-week placebo washout phase. The initial dose in all patients was 8 mg/day p.o.; this was doubled to 16 mg once daily if an adequate blood pressure reduction was not achieved after 10 days on 8 mg. The objective of the study was to investigate the effect of this new calcium antagonist on the blood pressure in hypertensive patients. This was done by means of a 24-h blood pressure profile (with measurements at 0.5, 1, 2, 4, 8, 12, and 24 h after administration), and over the complete course of the treatment period (blood pressure measurements each day just before the medication was given). In addition, by determination of the nilvadipine plasma levels on the first, tenth, and last medication day, a possible concentration-efficacy relationship was to be ascertained between plasma concentration of nilvadipine and the observed blood pressure-lowering effect of the drug. Adequate blood pressure reductions were achieved with nilvadipine 8 mg once daily in 13 patients; 7 required a doubling of the dosage to 16 mg/day. Already on the first day of therapy, both the systolic and diastolic blood pressures were significantly reduced compared to those in the placebo phase (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283188", "title": "Comparison of the efficacy of nilvadipine and nitrendipine on circadian blood pressure.", "content": "The efficacy of nilvadipine and nitrendipine was compared in two double-blind, placebo-controlled trials. Patients had either mild-to-moderate hypertension (study 1) or moderate hypertension that was difficult to control (study 2). The criterion for efficacy was a mean drop in the median 24-h blood pressure profile after 10 days of medication compared with the placebo washout phase. Nilvadipine tended to be more efficacious than nitrendipine and had a significantly greater effect than placebo. The blood pressure reductions were more marked in the mild and moderate hypertension group than in patients with hypertension that was difficult to control. The hypotensive action of nilvadipine 16 mg lasted longer than that of nitrendipine 20 mg in all groups, especially in the group with difficult-to-control moderate hypertension. The response rate was somewhat higher in the nilvadipine group in both studies, particularly in patients with moderate hypertension that was difficult to control. Both substances were well tolerated, with fewer side effects noted for nilvadipine than for nitrendipine.", "contents": "Comparison of the efficacy of nilvadipine and nitrendipine on circadian blood pressure. The efficacy of nilvadipine and nitrendipine was compared in two double-blind, placebo-controlled trials. Patients had either mild-to-moderate hypertension (study 1) or moderate hypertension that was difficult to control (study 2). The criterion for efficacy was a mean drop in the median 24-h blood pressure profile after 10 days of medication compared with the placebo washout phase. Nilvadipine tended to be more efficacious than nitrendipine and had a significantly greater effect than placebo. The blood pressure reductions were more marked in the mild and moderate hypertension group than in patients with hypertension that was difficult to control. The hypotensive action of nilvadipine 16 mg lasted longer than that of nitrendipine 20 mg in all groups, especially in the group with difficult-to-control moderate hypertension. The response rate was somewhat higher in the nilvadipine group in both studies, particularly in patients with moderate hypertension that was difficult to control. Both substances were well tolerated, with fewer side effects noted for nilvadipine than for nitrendipine."} {"id": "PMID:1283189", "title": "The role of calcium antagonists in the treatment of hypertension.", "content": "Calcium antagonists are of particular importance in the treatment of hypertension because they influence the free cytoplasmic calcium concentration and thereby many pressor mechanisms in the smooth muscle cell. A fall in the peripheral resistance is the main hemodynamic effect, and this is more marked with the second-generation calcium antagonists because they are more vasoselective than the first calcium-channel blockers. Particularly important is their lack of effect on lipid and glucose metabolism, as well as the absence of serious side effects. It has not yet been possible to confirm that the antiatherogenic effect found in some animal models also occurs in humans. Calcium antagonists are effective, safe, and well-tolerated antihypertensive agents that can be combined with all other antihypertensives with the exception of the combination of verapamil and a beta-blocker. They are easy to dose for individualized \"stepped\" therapy. They have a particular role in hypertensive patients with cardiac effects secondary to hypertension, coronary artery disease, obstructive bronchial diseases, diabetes, renal disease, and peripheral arterial occlusive disease.", "contents": "The role of calcium antagonists in the treatment of hypertension. Calcium antagonists are of particular importance in the treatment of hypertension because they influence the free cytoplasmic calcium concentration and thereby many pressor mechanisms in the smooth muscle cell. A fall in the peripheral resistance is the main hemodynamic effect, and this is more marked with the second-generation calcium antagonists because they are more vasoselective than the first calcium-channel blockers. Particularly important is their lack of effect on lipid and glucose metabolism, as well as the absence of serious side effects. It has not yet been possible to confirm that the antiatherogenic effect found in some animal models also occurs in humans. Calcium antagonists are effective, safe, and well-tolerated antihypertensive agents that can be combined with all other antihypertensives with the exception of the combination of verapamil and a beta-blocker. They are easy to dose for individualized \"stepped\" therapy. They have a particular role in hypertensive patients with cardiac effects secondary to hypertension, coronary artery disease, obstructive bronchial diseases, diabetes, renal disease, and peripheral arterial occlusive disease."} {"id": "PMID:1283190", "title": "Hypertensive heart disease--significance of left ventricular hypertrophy.", "content": "One of the earliest structural changes in the heart adapting to hypertension is left ventricular hypertrophy, which can now be exactly measured by echocardiography. Left ventricular hypertrophy increases the incidence of coronary artery disease, heart failure, and sudden death severalfold, independent of the blood pressure levels. Left ventricular hypertrophy requires specific antihypertensive therapy that controls both high blood pressure and increased left ventricular mass. Preliminary data from clinical studies indicate that regression of left ventricular hypertrophy leads to a better cardiovascular prognosis. Sympatholytic substances, angiotensin-converting enzyme (ACE) inhibitors, and calcium antagonists are antihypertensive agents that effected adequate reductions in blood pressure as well as regression of left ventricular hypertrophy.", "contents": "Hypertensive heart disease--significance of left ventricular hypertrophy. One of the earliest structural changes in the heart adapting to hypertension is left ventricular hypertrophy, which can now be exactly measured by echocardiography. Left ventricular hypertrophy increases the incidence of coronary artery disease, heart failure, and sudden death severalfold, independent of the blood pressure levels. Left ventricular hypertrophy requires specific antihypertensive therapy that controls both high blood pressure and increased left ventricular mass. Preliminary data from clinical studies indicate that regression of left ventricular hypertrophy leads to a better cardiovascular prognosis. Sympatholytic substances, angiotensin-converting enzyme (ACE) inhibitors, and calcium antagonists are antihypertensive agents that effected adequate reductions in blood pressure as well as regression of left ventricular hypertrophy."} {"id": "PMID:1283191", "title": "The tolerability of nilvadipine compared to nifedipine in patients with essential hypertension.", "content": "In one multicenter, double-blind study, 659 hypertensive patients were treated for 16 weeks with either nilvadipine (n = 326) or nifedipine (n = 333). The major objective of the study was to compare the compatibility of the two calcium antagonists with regard to hepatic compatibility and side-effect profiles. The dosages were chosen so that the effective blood pressure reduction in both groups was equally good (mean decreases in systolic pressure of 27 +/- 12 mm Hg with nilvadipine and 26 +/- 15 mm Hg with nifedipine, and in diastolic pressure of 18 +/- 6 mm Hg with nilvadipine and 19 +/- 7 mm Hg with nifedipine). The mean heart rate was slightly lowered by about 2 beats/min by both substances. Although there was no effect on lipid or glucose levels, the serum glutamate-pyruvate transaminase (SPGT) levels were more often found to be raised in the nifedipine group than in the nilvadipine group (p < 0.05). The vasodilator effect of both calcium antagonists was responsible for side effects, of which the most common were flushing, edema, headache, and palpitations. The number of complaints was less in the group treated with nilvadipine than with nifedipine, especially flushing and edema. Significantly more patients in the nifedipine group withdrew from treatment due to undesirable side effects (p < 0.05).", "contents": "The tolerability of nilvadipine compared to nifedipine in patients with essential hypertension. In one multicenter, double-blind study, 659 hypertensive patients were treated for 16 weeks with either nilvadipine (n = 326) or nifedipine (n = 333). The major objective of the study was to compare the compatibility of the two calcium antagonists with regard to hepatic compatibility and side-effect profiles. The dosages were chosen so that the effective blood pressure reduction in both groups was equally good (mean decreases in systolic pressure of 27 +/- 12 mm Hg with nilvadipine and 26 +/- 15 mm Hg with nifedipine, and in diastolic pressure of 18 +/- 6 mm Hg with nilvadipine and 19 +/- 7 mm Hg with nifedipine). The mean heart rate was slightly lowered by about 2 beats/min by both substances. Although there was no effect on lipid or glucose levels, the serum glutamate-pyruvate transaminase (SPGT) levels were more often found to be raised in the nifedipine group than in the nilvadipine group (p < 0.05). The vasodilator effect of both calcium antagonists was responsible for side effects, of which the most common were flushing, edema, headache, and palpitations. The number of complaints was less in the group treated with nilvadipine than with nifedipine, especially flushing and edema. Significantly more patients in the nifedipine group withdrew from treatment due to undesirable side effects (p < 0.05)."} {"id": "PMID:1283192", "title": "Comparisons of once-daily nilvadipine with enalapril and diuretic in patients with essential hypertension.", "content": "The antihypertensive efficacy of the new dihydropyridine derivative nilvadipine given once daily was compared in two randomized, double-blind studies with that of hydrochlorothiazide/triamterene (HCT/T) and of enalapril. In the first study, arterial pressures were compared after 4 weeks of therapy with nilvadipine (16 mg q.d.) or HCT/T (25/50 mg q.d.) in patients with mild-to-moderate hypertension in a parallel-group design. The combination of both treatments was administered after 4 weeks if diastolic arterial pressures were > 90 mm Hg. The blood pressure (BP) in the nilvadipine group (n = 125) was 161/102 +/- 17/7 (mean +/- SD) mm Hg after a 2-week placebo period and decreased after 4 weeks by -16/-13 +/- 22/12 mm Hg. The BP decreased in the HCT/T group (n = 124) compared to the nilvadipine group to a similar degree (p = 0.91, n.s.) from 160/103 +/- 17/8 mm Hg by -17/-13 +/- 18/11 mm Hg. A combination therapy was started after 4 weeks in 39 patients in the nilvadipine group and in 34 patients in the HCT/T group. This led independently of the treatment sequence, to a similar decrease in BP in the nilvadipine group (-17/7 +/- 16/10 mm Hg) and in the HCT/T group (-12/9 +/- 16/9 mm Hg). In the second study, the antihypertensive effect of nilvadipine (1 x .8 mg) was compared with that of enalapril (1 x 10 mg) in a randomized, double-blind, crossover design. Sixty-one patients with essential hypertension (WHO I-II) were treated over two 4-week periods following placebo periods of 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Comparisons of once-daily nilvadipine with enalapril and diuretic in patients with essential hypertension. The antihypertensive efficacy of the new dihydropyridine derivative nilvadipine given once daily was compared in two randomized, double-blind studies with that of hydrochlorothiazide/triamterene (HCT/T) and of enalapril. In the first study, arterial pressures were compared after 4 weeks of therapy with nilvadipine (16 mg q.d.) or HCT/T (25/50 mg q.d.) in patients with mild-to-moderate hypertension in a parallel-group design. The combination of both treatments was administered after 4 weeks if diastolic arterial pressures were > 90 mm Hg. The blood pressure (BP) in the nilvadipine group (n = 125) was 161/102 +/- 17/7 (mean +/- SD) mm Hg after a 2-week placebo period and decreased after 4 weeks by -16/-13 +/- 22/12 mm Hg. The BP decreased in the HCT/T group (n = 124) compared to the nilvadipine group to a similar degree (p = 0.91, n.s.) from 160/103 +/- 17/8 mm Hg by -17/-13 +/- 18/11 mm Hg. A combination therapy was started after 4 weeks in 39 patients in the nilvadipine group and in 34 patients in the HCT/T group. This led independently of the treatment sequence, to a similar decrease in BP in the nilvadipine group (-17/7 +/- 16/10 mm Hg) and in the HCT/T group (-12/9 +/- 16/9 mm Hg). In the second study, the antihypertensive effect of nilvadipine (1 x .8 mg) was compared with that of enalapril (1 x 10 mg) in a randomized, double-blind, crossover design. Sixty-one patients with essential hypertension (WHO I-II) were treated over two 4-week periods following placebo periods of 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283193", "title": "The effect of antihypertensive therapy on the course of renal failure.", "content": "The course and prognosis of chronic renal failure are much worse in hypertensive patients than in normotensive patients with otherwise similar basic disease. Therefore, antihypertensive measures with a combination of diuretics, beta-blockers, and vasodilators have clearly been shown to improve the progression of diabetic nephropathy. Treatment of hypertension with angiotensin-converting enzyme (ACE) inhibitors has also been shown to have a favorable effect on the prognosis of chronic renal failure. In the past few years, more knowledge about the pathogenesis of hypertension and the development of hypertension-induced organ damage has been followed by changing attitudes to antihypertensive therapy and the introduction of calcium antagonists for the treatment of hypertension, even in chronic renal failure. ACE inhibitors and calcium antagonists seem to be advantageous in the prognosis of chronic renal failure as they act on the humoral and trophogenic factors now known to be important in antihypertensive therapy.", "contents": "The effect of antihypertensive therapy on the course of renal failure. The course and prognosis of chronic renal failure are much worse in hypertensive patients than in normotensive patients with otherwise similar basic disease. Therefore, antihypertensive measures with a combination of diuretics, beta-blockers, and vasodilators have clearly been shown to improve the progression of diabetic nephropathy. Treatment of hypertension with angiotensin-converting enzyme (ACE) inhibitors has also been shown to have a favorable effect on the prognosis of chronic renal failure. In the past few years, more knowledge about the pathogenesis of hypertension and the development of hypertension-induced organ damage has been followed by changing attitudes to antihypertensive therapy and the introduction of calcium antagonists for the treatment of hypertension, even in chronic renal failure. ACE inhibitors and calcium antagonists seem to be advantageous in the prognosis of chronic renal failure as they act on the humoral and trophogenic factors now known to be important in antihypertensive therapy."} {"id": "PMID:1283194", "title": "Nilvadipine in hypertension with renal dysfunction.", "content": "The pharmacokinetics and pharmacodynamics of nilvadipine, a new dihydropyridine calcium antagonist, were examined in 16 patients divided into two different population groups. The first group of eight patients had arterial hypertension with limited renal function (creatinine clearance of 15-50 ml/min). The second group of eight patients had arterial hypertension with no concomitant renal dysfunction (creatinine clearance over 80 ml/min). Following a 1-week placebo washout period, all patients were given 8 mg of nilvadipine once daily for 10 days. The diastolic blood pressure (24-h postdose) fell in group I from a mean of 100.5 to 91.5 mm Hg and in group II from a mean of 106.7 to 88.2 mm Hg, which was significant in comparison to the placebo period. In neither group was there a significant change in heart rate, renin and aldosterone plasma levels, serum electrolytes, or sodium and potassium excretion. The pharmacokinetics of the unchanged nilvadipine were not significantly different between group I and group II. Neither group showed unchanged nilvadipine in urine. There was a slight increase in plasma levels of the inactive main metabolites M3 and M7; there was correspondingly less M3 found in the urine of group I patients. Nilvadipine appears to be an effective hypotensive agent at single daily doses of 8 mg. This dosage was well tolerated. The findings of this study did not suggest that lower doses need to be given to patients with limited renal function, at least not those with a creatinine clearance between 15 and 50 ml/min.", "contents": "Nilvadipine in hypertension with renal dysfunction. The pharmacokinetics and pharmacodynamics of nilvadipine, a new dihydropyridine calcium antagonist, were examined in 16 patients divided into two different population groups. The first group of eight patients had arterial hypertension with limited renal function (creatinine clearance of 15-50 ml/min). The second group of eight patients had arterial hypertension with no concomitant renal dysfunction (creatinine clearance over 80 ml/min). Following a 1-week placebo washout period, all patients were given 8 mg of nilvadipine once daily for 10 days. The diastolic blood pressure (24-h postdose) fell in group I from a mean of 100.5 to 91.5 mm Hg and in group II from a mean of 106.7 to 88.2 mm Hg, which was significant in comparison to the placebo period. In neither group was there a significant change in heart rate, renin and aldosterone plasma levels, serum electrolytes, or sodium and potassium excretion. The pharmacokinetics of the unchanged nilvadipine were not significantly different between group I and group II. Neither group showed unchanged nilvadipine in urine. There was a slight increase in plasma levels of the inactive main metabolites M3 and M7; there was correspondingly less M3 found in the urine of group I patients. Nilvadipine appears to be an effective hypotensive agent at single daily doses of 8 mg. This dosage was well tolerated. The findings of this study did not suggest that lower doses need to be given to patients with limited renal function, at least not those with a creatinine clearance between 15 and 50 ml/min."} {"id": "PMID:1283195", "title": "In situ hybridisation: a review of methodologies and applications in the biomedical sciences.", "content": "In situ hybridisation methodology is reviewed with particular emphasis on the latest modifications of technique. Methodology is evaluated, with suggestions on how to maximise its successful application. Emphasis is placed upon non-radioactive techniques which can be used by morphologically orientated laboratories, and details of the use of digoxigenin-labelled oligonucleotide probes are given special mention. Recent applications in morphology, and neurobiology, virology, pathology and cytogenetics are detailed. Developments where significant advances have been made in the biomedical sciences are highlighted.", "contents": "In situ hybridisation: a review of methodologies and applications in the biomedical sciences. In situ hybridisation methodology is reviewed with particular emphasis on the latest modifications of technique. Methodology is evaluated, with suggestions on how to maximise its successful application. Emphasis is placed upon non-radioactive techniques which can be used by morphologically orientated laboratories, and details of the use of digoxigenin-labelled oligonucleotide probes are given special mention. Recent applications in morphology, and neurobiology, virology, pathology and cytogenetics are detailed. Developments where significant advances have been made in the biomedical sciences are highlighted."} {"id": "PMID:1283196", "title": "A modified Ziehl-Neelsen stain for mycobacteria.", "content": "For the preliminary detection of mycobacteria in routine pathology specimens heavy reliance is placed on staining methods. Difficulties encountered with a cold-staining method, which had possibly gone un-noticed for several years despite a quality control check programme, are described. An alternative to the 'classical' Ziehl-Neelsen stain is described, which although devised initially as a 'stop-gap' is still in use eight years later.", "contents": "A modified Ziehl-Neelsen stain for mycobacteria. For the preliminary detection of mycobacteria in routine pathology specimens heavy reliance is placed on staining methods. Difficulties encountered with a cold-staining method, which had possibly gone un-noticed for several years despite a quality control check programme, are described. An alternative to the 'classical' Ziehl-Neelsen stain is described, which although devised initially as a 'stop-gap' is still in use eight years later."} {"id": "PMID:1283198", "title": "Spinal versus epidural anesthesia during transurethral resection of the prostate.", "content": "The operative superiority of epidural anesthesia during transurethral resection of the prostate (TURP) stimulated this study. Twenty patients scheduled for TURP were randomly allocated to receive either spinal anesthesia (n = 10) with 8 ml bupivacaine 0.5%+ 5ml lignocaine 2%. During and after the operative procedure, PR, BP, ECG, and pulse oximetry were monitored, and blood Hb and Hct, plasma free Hb, and serum sodium and potassium levels were measured. Both techniques resulted in similar PR and BP changes. TURP with spinal anesthesia resulted in more prolonged period of hyponatremia and more increased duration of raised plasma free Hb.", "contents": "Spinal versus epidural anesthesia during transurethral resection of the prostate. The operative superiority of epidural anesthesia during transurethral resection of the prostate (TURP) stimulated this study. Twenty patients scheduled for TURP were randomly allocated to receive either spinal anesthesia (n = 10) with 8 ml bupivacaine 0.5%+ 5ml lignocaine 2%. During and after the operative procedure, PR, BP, ECG, and pulse oximetry were monitored, and blood Hb and Hct, plasma free Hb, and serum sodium and potassium levels were measured. Both techniques resulted in similar PR and BP changes. TURP with spinal anesthesia resulted in more prolonged period of hyponatremia and more increased duration of raised plasma free Hb."} {"id": "PMID:1283199", "title": "Molecular cloning, nucleotide sequence and expression of a cDNA encoding an intracellular protein tyrosine phosphatase, PTPase-2, from mouse testis and T-cells.", "content": "The PTP-2 cDNA encoding an intracellular protein tyrosine phosphatase (PTPase-2) was isolated and sequenced from mouse testis and T-cell cDNA libraries. This PTP-2 cDNA was found to be homologous to human PTP-TC and rat PTP-S, and contained 1,551 nucleotides, including 1,146 nucleotides encoding 382 amino acids as well as 5' (61 nucleotides) and 3' (344 nucleotides) non-coding regions. Northern blot analysis indicated that PTP-2 mRNA of 1.9 Kb was most abundant in testis and kidney, although it was also present in spleen, muscle, liver, heart and brain.", "contents": "Molecular cloning, nucleotide sequence and expression of a cDNA encoding an intracellular protein tyrosine phosphatase, PTPase-2, from mouse testis and T-cells. The PTP-2 cDNA encoding an intracellular protein tyrosine phosphatase (PTPase-2) was isolated and sequenced from mouse testis and T-cell cDNA libraries. This PTP-2 cDNA was found to be homologous to human PTP-TC and rat PTP-S, and contained 1,551 nucleotides, including 1,146 nucleotides encoding 382 amino acids as well as 5' (61 nucleotides) and 3' (344 nucleotides) non-coding regions. Northern blot analysis indicated that PTP-2 mRNA of 1.9 Kb was most abundant in testis and kidney, although it was also present in spleen, muscle, liver, heart and brain."} {"id": "PMID:1283200", "title": "Development of infants with disabilities and their families: implications for theory and service delivery.", "content": "This Monograph presents the results of a nonexperimental, longitudinal investigation of developmental change in 190 infants and their families after 1 year of early intervention services. The Early Intervention Collaborative Study (EICS), conducted in association with 29 community-based programs in Massachusetts and New Hampshire, was designed to assess correlates of adaptation in young children with disabilities and their families over time, to inform social policy by analyzing the influences of family ecology and formal services on child and family outcomes, and to generate conceptual models to guide further investigation. The study sample (mean age at entry = 10.6 months) includes 54 children with Down syndrome, 77 with motor impairment, and 59 with developmental delays of uncertain etiology. Data were collected during two home visits (within 6 weeks of program entry and 12 months later) and included formal child assessments, observations of mother-child interaction, maternal interviews, and questionnaires completed independently by both parents as well as monthly service data collected from service providers. Child and family functioning varied considerably. Developmental change in the children (psychomotor abilities, adaptive behavior, spontaneous play, and child-mother interaction skills) was influenced to some extent by gestational age and health characteristics, but the strongest predictor of change was the relative severity of the child's psychomotor impairment at study entry. Families demonstrated generally positive and stable adaptation (in terms of the effect of rearing a child with disabilities on the family, parenting stress, and social support), despite persistent challenges with respect to mother-child interaction and differences in reported stress between mothers and fathers. Documentation of services revealed that early intervention is a complex and multidimensional experience that spans multiple public and private systems. Vulnerable and resilient subgroups within the sample were identified, and different correlates of adaptive change were demonstrated. Results of data analyses suggest new perspectives on the study of early childhood disability. The implications of the findings for developmental theory and social policy are discussed.", "contents": "Development of infants with disabilities and their families: implications for theory and service delivery. This Monograph presents the results of a nonexperimental, longitudinal investigation of developmental change in 190 infants and their families after 1 year of early intervention services. The Early Intervention Collaborative Study (EICS), conducted in association with 29 community-based programs in Massachusetts and New Hampshire, was designed to assess correlates of adaptation in young children with disabilities and their families over time, to inform social policy by analyzing the influences of family ecology and formal services on child and family outcomes, and to generate conceptual models to guide further investigation. The study sample (mean age at entry = 10.6 months) includes 54 children with Down syndrome, 77 with motor impairment, and 59 with developmental delays of uncertain etiology. Data were collected during two home visits (within 6 weeks of program entry and 12 months later) and included formal child assessments, observations of mother-child interaction, maternal interviews, and questionnaires completed independently by both parents as well as monthly service data collected from service providers. Child and family functioning varied considerably. Developmental change in the children (psychomotor abilities, adaptive behavior, spontaneous play, and child-mother interaction skills) was influenced to some extent by gestational age and health characteristics, but the strongest predictor of change was the relative severity of the child's psychomotor impairment at study entry. Families demonstrated generally positive and stable adaptation (in terms of the effect of rearing a child with disabilities on the family, parenting stress, and social support), despite persistent challenges with respect to mother-child interaction and differences in reported stress between mothers and fathers. Documentation of services revealed that early intervention is a complex and multidimensional experience that spans multiple public and private systems. Vulnerable and resilient subgroups within the sample were identified, and different correlates of adaptive change were demonstrated. Results of data analyses suggest new perspectives on the study of early childhood disability. The implications of the findings for developmental theory and social policy are discussed."} {"id": "PMID:1283202", "title": "Abnormal distribution of desmin and vimentin in myofibers in adult onset myotubular myopathy.", "content": "We report, for the first time, muscle immunocytochemical studies in sporadic, adult onset myotubular myopathy (SAOMM), which show intramyofibrillar central, perinuclear desmin and vimentin. This pattern was absent in a normal control and in myofibers with increased internal nuclei associated with denervation and myotonic muscular dystrophy (MyD). These findings resemble those reported in 8- to 15-week-old human fetal myotubes and myofibers of infantile MM, implying a possible regression of intermediate filaments of adult myofibers to an early developmental phase in SAOMM.", "contents": "Abnormal distribution of desmin and vimentin in myofibers in adult onset myotubular myopathy. We report, for the first time, muscle immunocytochemical studies in sporadic, adult onset myotubular myopathy (SAOMM), which show intramyofibrillar central, perinuclear desmin and vimentin. This pattern was absent in a normal control and in myofibers with increased internal nuclei associated with denervation and myotonic muscular dystrophy (MyD). These findings resemble those reported in 8- to 15-week-old human fetal myotubes and myofibers of infantile MM, implying a possible regression of intermediate filaments of adult myofibers to an early developmental phase in SAOMM."} {"id": "PMID:1283203", "title": "Expression of glial fibrillary acidic protein (GFAP) by cultured angiofibroma stroma cells from patients with tuberous sclerosis.", "content": "Large dendritic cells were cultured from facial angiofibromas of six patients with tuberous sclerosis. The cells were examined immunocytochemically for expression of selected cytoskeletal and non-structural proteins and the results compared with the staining profiles obtained with normal skin fibroblasts and normal glial cells. In similarity to normal glia, the angiofibroma stroma cells expressed glial fibrillary acidic protein (GFAP). Conversely, by analogy to fibroblasts, the abnormal stroma cells produced fibronectin and did not react with the antibody to S-100 protein. By immunogold labelling it was established that GFAP and vimentin were co-localized in intermediate filaments of the angiofibroma cells.", "contents": "Expression of glial fibrillary acidic protein (GFAP) by cultured angiofibroma stroma cells from patients with tuberous sclerosis. Large dendritic cells were cultured from facial angiofibromas of six patients with tuberous sclerosis. The cells were examined immunocytochemically for expression of selected cytoskeletal and non-structural proteins and the results compared with the staining profiles obtained with normal skin fibroblasts and normal glial cells. In similarity to normal glia, the angiofibroma stroma cells expressed glial fibrillary acidic protein (GFAP). Conversely, by analogy to fibroblasts, the abnormal stroma cells produced fibronectin and did not react with the antibody to S-100 protein. By immunogold labelling it was established that GFAP and vimentin were co-localized in intermediate filaments of the angiofibroma cells."} {"id": "PMID:1283204", "title": "An assessment of the proliferative potential of 'balloon cells' in focal cortical resections performed for childhood epilepsy.", "content": "Cerebral cortical dysplasia is an uncommon pathological substrate of severe intractable childhood epilepsy, sometimes treated by hemispherectomy. Neuropathological findings include abnormal gyrus formation, loss of cortical lamination, unusual giant neurons and 'balloon cells' of indeterminate histogenesis similar in appearance to neoplastic gemistocytic astrocytes. In order to investigate the proliferative potential of 'balloon cells', we used Crocker's silver impregnation technique to demonstrate nucleolar organizer regions (AgNORs) involved in cellular proliferation, together with immunohistochemical evaluation of proliferating cell nuclear antigen (PCNA) expression. Balloon cells (5.56 +/- 0.24) had significantly (P < 0.001) greater AgNOR numbers than reactive astrocytes (3.89 +/- 0.15), neurons (2.30 +/- 0.13) or giant neurons (4.26 +/- 0.20). However, when corrected for nuclear size, results showed that 'balloon cells' (0.093 +/- 0.006) had significantly (P < 0.001) fewer AgNORs/square micrometre of nuclear area than reactive astrocytes (0.225 +/- 0.016) and had significantly (P < 0.001) more AgNORs/square micrometre of nuclear area than normal (0.048 +/- 0.003) or giant neurons (0.054 +/- 0.003). On the assumption that astrocytes are typical interphase cells and that normal neurons are post-mitotic, the results suggest that 'balloon cells' are unlikely to be undergoing proliferative activity and, when adjusted for nuclear size, the number of AgNORs/unit of nuclear area is more reflective of cellular ploidy than of proliferative activity in non-neoplastic neural tissues. The virtual absence of PCNA expression by 'balloon cell' nuclei supports such an interpretation of the AgNOR results.", "contents": "An assessment of the proliferative potential of 'balloon cells' in focal cortical resections performed for childhood epilepsy. Cerebral cortical dysplasia is an uncommon pathological substrate of severe intractable childhood epilepsy, sometimes treated by hemispherectomy. Neuropathological findings include abnormal gyrus formation, loss of cortical lamination, unusual giant neurons and 'balloon cells' of indeterminate histogenesis similar in appearance to neoplastic gemistocytic astrocytes. In order to investigate the proliferative potential of 'balloon cells', we used Crocker's silver impregnation technique to demonstrate nucleolar organizer regions (AgNORs) involved in cellular proliferation, together with immunohistochemical evaluation of proliferating cell nuclear antigen (PCNA) expression. Balloon cells (5.56 +/- 0.24) had significantly (P < 0.001) greater AgNOR numbers than reactive astrocytes (3.89 +/- 0.15), neurons (2.30 +/- 0.13) or giant neurons (4.26 +/- 0.20). However, when corrected for nuclear size, results showed that 'balloon cells' (0.093 +/- 0.006) had significantly (P < 0.001) fewer AgNORs/square micrometre of nuclear area than reactive astrocytes (0.225 +/- 0.016) and had significantly (P < 0.001) more AgNORs/square micrometre of nuclear area than normal (0.048 +/- 0.003) or giant neurons (0.054 +/- 0.003). On the assumption that astrocytes are typical interphase cells and that normal neurons are post-mitotic, the results suggest that 'balloon cells' are unlikely to be undergoing proliferative activity and, when adjusted for nuclear size, the number of AgNORs/unit of nuclear area is more reflective of cellular ploidy than of proliferative activity in non-neoplastic neural tissues. The virtual absence of PCNA expression by 'balloon cell' nuclei supports such an interpretation of the AgNOR results."} {"id": "PMID:1283205", "title": "Comparison of modified Bielschowsky silver impregnation and anti-ubiquitin immunostaining of cortical and nigral Lewy bodies.", "content": "We have compared the sensitivity of a modified Bielschowsky silver impregnation with that of anti-ubiquitin immunostaining for the detection of Lewy bodies in five cases of diffuse Lewy body disease. In two of the cases there were neuritic plaques and neurofibrillary tangles within the neocortex in sufficient numbers to warrant an additional diagnosis of Alzheimer's disease. The modified Bielschowsky technique was as effective as anti-ubiquitin immunohistochemistry at demonstrating cortical Lewy bodies in 7 micron-thick paraffin sections. As might therefore be expected, silver impregnation of 20 micron-thick sections revealed significantly more cortical Lewy bodies than did the immunostaining of 7 micron-thick sections (P = 0.004). The silver impregnation had the further advantage of allowing much better visualization of the Alzheimer-type changes. In contrast to the cortical-type Lewy bodies, the dense-core type present in sections of midbrain were relatively poorly impregnated by the modified Bielschowsky method, possibly reflecting differences in the composition of the two types of inclusion.", "contents": "Comparison of modified Bielschowsky silver impregnation and anti-ubiquitin immunostaining of cortical and nigral Lewy bodies. We have compared the sensitivity of a modified Bielschowsky silver impregnation with that of anti-ubiquitin immunostaining for the detection of Lewy bodies in five cases of diffuse Lewy body disease. In two of the cases there were neuritic plaques and neurofibrillary tangles within the neocortex in sufficient numbers to warrant an additional diagnosis of Alzheimer's disease. The modified Bielschowsky technique was as effective as anti-ubiquitin immunohistochemistry at demonstrating cortical Lewy bodies in 7 micron-thick paraffin sections. As might therefore be expected, silver impregnation of 20 micron-thick sections revealed significantly more cortical Lewy bodies than did the immunostaining of 7 micron-thick sections (P = 0.004). The silver impregnation had the further advantage of allowing much better visualization of the Alzheimer-type changes. In contrast to the cortical-type Lewy bodies, the dense-core type present in sections of midbrain were relatively poorly impregnated by the modified Bielschowsky method, possibly reflecting differences in the composition of the two types of inclusion."} {"id": "PMID:1283206", "title": "Response of hypothalamic peptide mRNAs to thyroidectomy.", "content": "Using in situ hybridization histochemistry, we have investigated the effect of thyroid hormone on the expression of several peptide mRNAs in the hypothalamic paraventricular nucleus (PVN) of adult male rats. Hypothyroidism was induced by surgical ablation of the thyroid gland. The animals (control sham-operated, thyroidectomized, thyroidectomized+T4 replaced rats) were studied 28 and 50 days after surgery. Sections of the PVN were hybridized using synthetic oligonucleotide probes complementary to mRNA for thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), galanin (GAL), enkephalin (ENK), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and vasopressin (VP). GAL mRNA was also analyzed in the anterior paraventricular, arcuate, and dorsomedial nuclei of the hypothalamus. At the PVN level, a feedback effect of thyroid hormone on TRH synthesis was demonstrated by the TRH mRNA increase in hypothyroidism and by its decrease in hyperthyroidism. Hypothyroidism caused a dramatic decrease in GAL mRNA in parvo- and magnocellular PVN neurons both 28 and 50 days after thyroid ablation, whereas no effect was seen in VP mRNA, the main peptide hormone coexisting with GAL. The T4 replacement prevented the GAL mRNA impairment. Hypothyroidism did not influence GAL mRNA in the anterior PVN, perifornical area or in the arcuate nucleus, whereas a decrease in GAL mRNA was observed in the dorsomedial nucleus. VIP mRNA, which is undetectable in the PVN of normal animals, was present in several PVN neurons after thyroidectomy. CRH mRNA was decreased after thyroidectomy, whereas the T4 restitution caused an upregulation. The levels of ENK or NT mRNA were not significantly affected by the thyroid status. The present results show that, in addition to TRH mRNA, other hypothalamic peptide mRNAs are affected by thyroid hormone levels.", "contents": "Response of hypothalamic peptide mRNAs to thyroidectomy. Using in situ hybridization histochemistry, we have investigated the effect of thyroid hormone on the expression of several peptide mRNAs in the hypothalamic paraventricular nucleus (PVN) of adult male rats. Hypothyroidism was induced by surgical ablation of the thyroid gland. The animals (control sham-operated, thyroidectomized, thyroidectomized+T4 replaced rats) were studied 28 and 50 days after surgery. Sections of the PVN were hybridized using synthetic oligonucleotide probes complementary to mRNA for thyrotropin-releasing hormone (TRH), corticotropin-releasing hormone (CRH), galanin (GAL), enkephalin (ENK), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and vasopressin (VP). GAL mRNA was also analyzed in the anterior paraventricular, arcuate, and dorsomedial nuclei of the hypothalamus. At the PVN level, a feedback effect of thyroid hormone on TRH synthesis was demonstrated by the TRH mRNA increase in hypothyroidism and by its decrease in hyperthyroidism. Hypothyroidism caused a dramatic decrease in GAL mRNA in parvo- and magnocellular PVN neurons both 28 and 50 days after thyroid ablation, whereas no effect was seen in VP mRNA, the main peptide hormone coexisting with GAL. The T4 replacement prevented the GAL mRNA impairment. Hypothyroidism did not influence GAL mRNA in the anterior PVN, perifornical area or in the arcuate nucleus, whereas a decrease in GAL mRNA was observed in the dorsomedial nucleus. VIP mRNA, which is undetectable in the PVN of normal animals, was present in several PVN neurons after thyroidectomy. CRH mRNA was decreased after thyroidectomy, whereas the T4 restitution caused an upregulation. The levels of ENK or NT mRNA were not significantly affected by the thyroid status. The present results show that, in addition to TRH mRNA, other hypothalamic peptide mRNAs are affected by thyroid hormone levels."} {"id": "PMID:1283207", "title": "Transient outward currents in cochlear ganglion neurons of the chick embryo.", "content": "Cochlear ganglion neurons were isolated from chick embryos and membrane currents recorded using the patch-clamp technique. Depolarizing voltage steps elicited transient outward currents whose inactivation was best fitted by a double-exponential function with time constants < 30 ms and > 100 ms. The fast inactivating transient outward current (Ito,f) had a threshold for activation of -61 +/- 5.5 mV; steady-state inactivation was voltage-dependent between -90 and -60 mV, with half-inactivation near -75 mV. The slowly inactivating outward current (Ito,s) showed an activation threshold of 34 +/- 4 mV. Half-inactivation was at -67 +/- 3 mV. Ito,f was blocked by 4-aminopyridine which did not affect Ito,s. The effect was concentration- and voltage-dependent. Tetraethylammonium had no effect on either fast or slow transient currents but reduced the amplitude of the non-inactivating outward current in a dose-dependent manner. Ito,f was strongly inhibited by removing Ca2+ from the extracellular bathing solution. Cobalt ions inhibited Ito,f in a dose-dependent manner between 2 and 20 mM. The inhibitory effect of Co2+ was voltage-dependent, displaying a bell-shaped inhibition curve as a function of membrane voltage, maximal inhibition occurring between -20 and 0 mV. Ca2+ removal did not affect Ito,s and partially reduced the amplitude of the steady-state current. These results provide kinetic and pharmacological evidence for the presence of two distinct transient outward currents in cochlear neurons. These currents may play a role in the first synaptic relay of sound transmission.", "contents": "Transient outward currents in cochlear ganglion neurons of the chick embryo. Cochlear ganglion neurons were isolated from chick embryos and membrane currents recorded using the patch-clamp technique. Depolarizing voltage steps elicited transient outward currents whose inactivation was best fitted by a double-exponential function with time constants < 30 ms and > 100 ms. The fast inactivating transient outward current (Ito,f) had a threshold for activation of -61 +/- 5.5 mV; steady-state inactivation was voltage-dependent between -90 and -60 mV, with half-inactivation near -75 mV. The slowly inactivating outward current (Ito,s) showed an activation threshold of 34 +/- 4 mV. Half-inactivation was at -67 +/- 3 mV. Ito,f was blocked by 4-aminopyridine which did not affect Ito,s. The effect was concentration- and voltage-dependent. Tetraethylammonium had no effect on either fast or slow transient currents but reduced the amplitude of the non-inactivating outward current in a dose-dependent manner. Ito,f was strongly inhibited by removing Ca2+ from the extracellular bathing solution. Cobalt ions inhibited Ito,f in a dose-dependent manner between 2 and 20 mM. The inhibitory effect of Co2+ was voltage-dependent, displaying a bell-shaped inhibition curve as a function of membrane voltage, maximal inhibition occurring between -20 and 0 mV. Ca2+ removal did not affect Ito,s and partially reduced the amplitude of the steady-state current. These results provide kinetic and pharmacological evidence for the presence of two distinct transient outward currents in cochlear neurons. These currents may play a role in the first synaptic relay of sound transmission."} {"id": "PMID:1283208", "title": "Spinal substance P and N-methyl-D-aspartate receptors are coactivated in the induction of central sensitization of the nociceptive flexor reflex.", "content": "We have studied the effects and interactions of the neurokinin-1 receptor antagonist CP-96,345 and the N-methyl-D-aspartate receptor/channel blocker MK-801, both applied intravenously, on the flexor reflex and on the facilitation of the flexor reflex by conditioning stimulation of cutaneous C-afferents in decerebrate, spinalized, unanesthetized rats. The flexor reflex was evoked by subcutaneous electrical stimuli applied to the sural nerve innervation area 1/min at an intensity that activated C-fibers and was recorded as electromyogram from the ipsilateral hamstring muscles. The magnitude of the baseline flexor reflex was usually highly stable in the course of the experiments without experimental manipulations. The same stimulus was used as a conditioning train (0.9 Hz, 20 shocks) and caused a brief facilitation of the flexor reflex, which was maximal 0.5 and 1 min after stimulation (255.1 +/- 23.6% over baseline). During the course of the conditioning stimulus train, the reflex magnitude was gradually increased (wind-up). MK-801 (0.1 and 0.5 mg/kg) consistently depressed the polysynaptic flexor reflex. At a dose of 0.5 mg/kg, but not 0.1 mg/kg, MK-801 reduced the wind-up and blocked the facilitation of the flexor reflex induced by the conditioning stimulus by 90%. The facilitatory effect of 7 pmol intrathecal substance P was also partially reduced by MK-801. CP 96,345 (1 and 3 mg/kg) did not depress the flexor reflex, but dose-dependently antagonized reflex facilitation by the conditioning stimulus train, similarly to its antagonism of intrathecally applied 7 pmol substance P-induced facilitation.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Spinal substance P and N-methyl-D-aspartate receptors are coactivated in the induction of central sensitization of the nociceptive flexor reflex. We have studied the effects and interactions of the neurokinin-1 receptor antagonist CP-96,345 and the N-methyl-D-aspartate receptor/channel blocker MK-801, both applied intravenously, on the flexor reflex and on the facilitation of the flexor reflex by conditioning stimulation of cutaneous C-afferents in decerebrate, spinalized, unanesthetized rats. The flexor reflex was evoked by subcutaneous electrical stimuli applied to the sural nerve innervation area 1/min at an intensity that activated C-fibers and was recorded as electromyogram from the ipsilateral hamstring muscles. The magnitude of the baseline flexor reflex was usually highly stable in the course of the experiments without experimental manipulations. The same stimulus was used as a conditioning train (0.9 Hz, 20 shocks) and caused a brief facilitation of the flexor reflex, which was maximal 0.5 and 1 min after stimulation (255.1 +/- 23.6% over baseline). During the course of the conditioning stimulus train, the reflex magnitude was gradually increased (wind-up). MK-801 (0.1 and 0.5 mg/kg) consistently depressed the polysynaptic flexor reflex. At a dose of 0.5 mg/kg, but not 0.1 mg/kg, MK-801 reduced the wind-up and blocked the facilitation of the flexor reflex induced by the conditioning stimulus by 90%. The facilitatory effect of 7 pmol intrathecal substance P was also partially reduced by MK-801. CP 96,345 (1 and 3 mg/kg) did not depress the flexor reflex, but dose-dependently antagonized reflex facilitation by the conditioning stimulus train, similarly to its antagonism of intrathecally applied 7 pmol substance P-induced facilitation.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283209", "title": "Direct projections from the central amygdaloid nucleus to the globus pallidus and substantia nigra in the cat.", "content": "Employing both anterograde and retrograde axonal tracing, we investigated direct projections from the central amygdaloid nucleus to the basal ganglia in the cat. The anterograde axonal tracing of Phaseolus vulgaris-leucoagglutinin revealed that projection fibers from the central amygdaloid nucleus to the basal ganglia ended in the globus pallidus (the feline homolog to the external segment of the globus pallidus of primates) and substantia nigra. The amygdalopallidal fibers terminated chiefly in the medial most part of the globus pallidus at its caudal level. The amygdalonigral fibers terminated densely in the substantia nigra pars lateralis, and moderately in the dorsolateral part of the substantia nigra pars reticulata; none of them were found to end in the substantia nigra pars compacta. Both of the amygdalopallidal and amygdalonigral projections were ipsilateral. These neuronal connections were confirmed by retrograde axonal tracing of cholera toxin B subunit in the second set of the experiments: The cells of origin of the amygdalopallidal and amygdalonigral projections were located predominantly in the lateral part of the central amygdaloid nucleus, and additionally in the intercalated cell islands of the amygdala. Most of them were of small bipolar or multipolar type. The cells projecting to the globus pallidus were preferentially distributed at the rostral levels of the central nucleus and intercalated cell islands of the amygdaloid complex, while those projecting to the substantia nigra were mainly located at the caudal levels of these amygdaloid subdivisions. In the third set of the experiments, sequential double-antigen immunofluorescence histochemistry for transported cholera toxin B subunit and horseradish peroxidase showed that some single neurons in the lateral part of the central amygdaloid nucleus, particularly at its middle level, issued axon collaterals to both the globus pallidus and substantia nigra pars lateralis. The results of the present study indicate that the central amygdaloid nucleus sends projection fibers to the globus pallidus and substantia nigra possibly to exert a limbic influence upon forebrain motor mechanisms.", "contents": "Direct projections from the central amygdaloid nucleus to the globus pallidus and substantia nigra in the cat. Employing both anterograde and retrograde axonal tracing, we investigated direct projections from the central amygdaloid nucleus to the basal ganglia in the cat. The anterograde axonal tracing of Phaseolus vulgaris-leucoagglutinin revealed that projection fibers from the central amygdaloid nucleus to the basal ganglia ended in the globus pallidus (the feline homolog to the external segment of the globus pallidus of primates) and substantia nigra. The amygdalopallidal fibers terminated chiefly in the medial most part of the globus pallidus at its caudal level. The amygdalonigral fibers terminated densely in the substantia nigra pars lateralis, and moderately in the dorsolateral part of the substantia nigra pars reticulata; none of them were found to end in the substantia nigra pars compacta. Both of the amygdalopallidal and amygdalonigral projections were ipsilateral. These neuronal connections were confirmed by retrograde axonal tracing of cholera toxin B subunit in the second set of the experiments: The cells of origin of the amygdalopallidal and amygdalonigral projections were located predominantly in the lateral part of the central amygdaloid nucleus, and additionally in the intercalated cell islands of the amygdala. Most of them were of small bipolar or multipolar type. The cells projecting to the globus pallidus were preferentially distributed at the rostral levels of the central nucleus and intercalated cell islands of the amygdaloid complex, while those projecting to the substantia nigra were mainly located at the caudal levels of these amygdaloid subdivisions. In the third set of the experiments, sequential double-antigen immunofluorescence histochemistry for transported cholera toxin B subunit and horseradish peroxidase showed that some single neurons in the lateral part of the central amygdaloid nucleus, particularly at its middle level, issued axon collaterals to both the globus pallidus and substantia nigra pars lateralis. The results of the present study indicate that the central amygdaloid nucleus sends projection fibers to the globus pallidus and substantia nigra possibly to exert a limbic influence upon forebrain motor mechanisms."} {"id": "PMID:1283210", "title": "Immunohistochemical localization of argininosuccinate synthetase in the rat brain in relation to nitric oxide synthase-containing neurons.", "content": "The distribution of the urea cycle enzyme, argininosuccinate synthetase, in the rat brain was determined using immunohistochemistry. This enzyme participates in the only known metabolic pathway for citrulline, its condensation with aspartate to form argininosuccinate, which can then be cleaved to fumarate and arginine. It may thus provide a mechanism to recycle citrulline, formed in the nervous system via nitric oxide synthase activity, back to the nitric oxide precursor, L-arginine. Argininosuccinate synthetase immunoreactivity was detected in discrete populations of neurons throughout the brain. Double-staining with nicotinamide adenine dinucleotide phosphate (reduced form)-diaphorase histochemistry for the localization of nitric oxide synthase demonstrated that argininosuccinate synthetase coexists with nitric oxide synthase in some brain regions. However, many neurons were found that contained one of these two enzymes, but not the other. Thus some nitric oxide synthase-containing neurons appear able to recycle citrulline via argininosuccinate, while others do not. Additional roles for argininosuccinate synthetase in the brain are discussed.", "contents": "Immunohistochemical localization of argininosuccinate synthetase in the rat brain in relation to nitric oxide synthase-containing neurons. The distribution of the urea cycle enzyme, argininosuccinate synthetase, in the rat brain was determined using immunohistochemistry. This enzyme participates in the only known metabolic pathway for citrulline, its condensation with aspartate to form argininosuccinate, which can then be cleaved to fumarate and arginine. It may thus provide a mechanism to recycle citrulline, formed in the nervous system via nitric oxide synthase activity, back to the nitric oxide precursor, L-arginine. Argininosuccinate synthetase immunoreactivity was detected in discrete populations of neurons throughout the brain. Double-staining with nicotinamide adenine dinucleotide phosphate (reduced form)-diaphorase histochemistry for the localization of nitric oxide synthase demonstrated that argininosuccinate synthetase coexists with nitric oxide synthase in some brain regions. However, many neurons were found that contained one of these two enzymes, but not the other. Thus some nitric oxide synthase-containing neurons appear able to recycle citrulline via argininosuccinate, while others do not. Additional roles for argininosuccinate synthetase in the brain are discussed."} {"id": "PMID:1283211", "title": "Histochemical localization of nitric oxide-synthesizing neurons and vascular sites in the guinea-pig intestine.", "content": "Laminar preparations of fixed segments of the guinea-pig intestine were examined for nitric oxide synthase activity using reduced nicotinamide adenine dinucleotide phosphate and nitroblue tetrazolium salt as substrates. Under conditions specific for detecting nitric oxide synthase-related diaphorase activity, a subpopulation of neural elements in the myenteric plexus, deep muscular plexus and submucosa were intensely stained. Intensely stained nerve fibres were distributed throughout the meshworks of the myenteric plexus and its innervation of the circular muscle, and in the submucosa within Henle's plexus. Intensely stained nerve cells and their processes were evident in most myenteric ganglia but were rare in ganglia of Henle's plexus. Stained ganglion cells comprised types I, II and VI of the morphologically defined enteric nerve cells. Stained neural elements were increasingly prevalent within successively more caudal segments of the intestine. In addition to neuronal staining, arterioles of the submucosal vascular network displayed distinct, punctate patches of staining distributed over their surface. Perivascular nerve fibre staining was absent. These results show nitric oxide synthase activity to be present within neurons and fibres of the major enteric nerve layers and within submucosal blood vessels throughout the guinea-pig small and large intestine.", "contents": "Histochemical localization of nitric oxide-synthesizing neurons and vascular sites in the guinea-pig intestine. Laminar preparations of fixed segments of the guinea-pig intestine were examined for nitric oxide synthase activity using reduced nicotinamide adenine dinucleotide phosphate and nitroblue tetrazolium salt as substrates. Under conditions specific for detecting nitric oxide synthase-related diaphorase activity, a subpopulation of neural elements in the myenteric plexus, deep muscular plexus and submucosa were intensely stained. Intensely stained nerve fibres were distributed throughout the meshworks of the myenteric plexus and its innervation of the circular muscle, and in the submucosa within Henle's plexus. Intensely stained nerve cells and their processes were evident in most myenteric ganglia but were rare in ganglia of Henle's plexus. Stained ganglion cells comprised types I, II and VI of the morphologically defined enteric nerve cells. Stained neural elements were increasingly prevalent within successively more caudal segments of the intestine. In addition to neuronal staining, arterioles of the submucosal vascular network displayed distinct, punctate patches of staining distributed over their surface. Perivascular nerve fibre staining was absent. These results show nitric oxide synthase activity to be present within neurons and fibres of the major enteric nerve layers and within submucosal blood vessels throughout the guinea-pig small and large intestine."} {"id": "PMID:1283212", "title": "Modulation of GABAA receptor-activated current by norepinephrine in cerebellar Purkinje cells.", "content": "Previous studies employing extracellular single-unit recording in the intact cerebellum have demonstrated that norepinephrine can potentiate GABA-induced suppression of Purkinje cell spike activity. However, many issues related to the nature of this modulatory phenomenon remain to be resolved. Using whole-cell patch clamp recording, the present study investigated the effect of norepinephrine on GABA-activated membrane currents (IGABA) in solitary Purkinje cells isolated from neonatal rat cerebella following acute dissociation. Exposure of Purkinje cells to norepinephrine at a concentration which, by itself, had no obvious effect on Purkinje cell membrane conductance, consistently augmented IGABA. The catecholamine also potentiated GABA-gated chloride currents as well as muscimol-induced currents in Purkinje cells. Thus, the facilitating effect of norepinephrine on IGABA was attributed to an interaction between norepinephrine and the GABAA receptor-mediated chloride conductance. The effect of norepinephrine could be mimicked by isoproterenol as well as by 8-bromo cAMP, suggesting that a beta-receptor-mediated, cAMP-dependent cascade may underlie the observed heteroreceptor interaction. Our results establish the existence of a postsynaptic mechanism by which norepinephrine, through activation of the beta-adrenoceptor, may modulate GABAA receptor function in cerebellar Purkinje cells. This study provides the groundwork for a detailed investigation into the cascade of membrane and intracellular events underlying such a synergistic modulatory interaction at the cellular and subcellular levels.", "contents": "Modulation of GABAA receptor-activated current by norepinephrine in cerebellar Purkinje cells. Previous studies employing extracellular single-unit recording in the intact cerebellum have demonstrated that norepinephrine can potentiate GABA-induced suppression of Purkinje cell spike activity. However, many issues related to the nature of this modulatory phenomenon remain to be resolved. Using whole-cell patch clamp recording, the present study investigated the effect of norepinephrine on GABA-activated membrane currents (IGABA) in solitary Purkinje cells isolated from neonatal rat cerebella following acute dissociation. Exposure of Purkinje cells to norepinephrine at a concentration which, by itself, had no obvious effect on Purkinje cell membrane conductance, consistently augmented IGABA. The catecholamine also potentiated GABA-gated chloride currents as well as muscimol-induced currents in Purkinje cells. Thus, the facilitating effect of norepinephrine on IGABA was attributed to an interaction between norepinephrine and the GABAA receptor-mediated chloride conductance. The effect of norepinephrine could be mimicked by isoproterenol as well as by 8-bromo cAMP, suggesting that a beta-receptor-mediated, cAMP-dependent cascade may underlie the observed heteroreceptor interaction. Our results establish the existence of a postsynaptic mechanism by which norepinephrine, through activation of the beta-adrenoceptor, may modulate GABAA receptor function in cerebellar Purkinje cells. This study provides the groundwork for a detailed investigation into the cascade of membrane and intracellular events underlying such a synergistic modulatory interaction at the cellular and subcellular levels."} {"id": "PMID:1283213", "title": "Transmitter diversity in carotid body afferent neurons: dopaminergic and peptidergic phenotypes.", "content": "Hypoxic stimulation of carotid body chemoreceptors is conveyed to the brainstem by primary sensory neurons whose peripheral axons run in the carotid sinus nerve. While considerable attention has focused on defining chemical neuroregulators released by glomus cells in the carotid body, our understanding of the morphology, distribution and transmitter phenotype of these carotid body afferent neurons remains limited. Carotid body afferent neurons were labeled by microinjection of the retrograde tracer, Fluorogold, into the vascularly isolated rat carotid body. In addition, immunoelectron microscopy was used to correlate transmitter phenotype with ultrastructural features of afferent terminals in the carotid body. Our results indicate that 41% of all carotid body afferent neurons express tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, whereas 7% contain substance P. Tyrosine hydroxylase- and substance P-positive neurons constitute separate subpopulations of carotid body afferents, as these two phenotypes were not colocalized. Most of the tyrosine hydroxylase-containing carotid body afferent neurons were small- or medium-sized (mean cell diameter 15-20 microns) and located in the distal petrosal ganglion, whereas the majority of substance P-containing carotid body afferent neurons were medium- to large-sized (mean cell diameter 20-29 microns) and located in the proximal petrosal ganglion and jugular ganglion. These differences strengthen the notion that these catecholaminergic and peptidergic carotid body afferent neurons give rise to functionally distinct subsets of chemoafferent fibers. To further characterize the catecholaminergic phenotype expressed by tyrosine hydroxylase-positive cells in the petrosal ganglion, we examined the colocalization of tyrosine hydroxylase and DOPA decarboxylase, the dopamine-synthesizing enzyme. Eighty-six per cent of tyrosine hydroxylase-positive neurons in the distal petrosal ganglion also contained DOPA decarboxylase; as these cells do not express the norepinephrine-synthesizing enzyme, dopamine beta-hydroxylase, these data indicate that the catecholaminergic carotid body afferent neurons are dopaminergic. Finally, ultrastructural analysis of the peripheral processes of tyrosine hydroxylase-positive afferent terminals in the carotid body demonstrated endings in close opposition to Type I glomus cells, consistent with a role for dopaminergic afferent neurons in carotid body chemoreception. One possibility is that these cells, in addition to their role as afferents, constitute a morphologic substrate for dopaminergic \"efferent\" inhibition in the carotid body.", "contents": "Transmitter diversity in carotid body afferent neurons: dopaminergic and peptidergic phenotypes. Hypoxic stimulation of carotid body chemoreceptors is conveyed to the brainstem by primary sensory neurons whose peripheral axons run in the carotid sinus nerve. While considerable attention has focused on defining chemical neuroregulators released by glomus cells in the carotid body, our understanding of the morphology, distribution and transmitter phenotype of these carotid body afferent neurons remains limited. Carotid body afferent neurons were labeled by microinjection of the retrograde tracer, Fluorogold, into the vascularly isolated rat carotid body. In addition, immunoelectron microscopy was used to correlate transmitter phenotype with ultrastructural features of afferent terminals in the carotid body. Our results indicate that 41% of all carotid body afferent neurons express tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, whereas 7% contain substance P. Tyrosine hydroxylase- and substance P-positive neurons constitute separate subpopulations of carotid body afferents, as these two phenotypes were not colocalized. Most of the tyrosine hydroxylase-containing carotid body afferent neurons were small- or medium-sized (mean cell diameter 15-20 microns) and located in the distal petrosal ganglion, whereas the majority of substance P-containing carotid body afferent neurons were medium- to large-sized (mean cell diameter 20-29 microns) and located in the proximal petrosal ganglion and jugular ganglion. These differences strengthen the notion that these catecholaminergic and peptidergic carotid body afferent neurons give rise to functionally distinct subsets of chemoafferent fibers. To further characterize the catecholaminergic phenotype expressed by tyrosine hydroxylase-positive cells in the petrosal ganglion, we examined the colocalization of tyrosine hydroxylase and DOPA decarboxylase, the dopamine-synthesizing enzyme. Eighty-six per cent of tyrosine hydroxylase-positive neurons in the distal petrosal ganglion also contained DOPA decarboxylase; as these cells do not express the norepinephrine-synthesizing enzyme, dopamine beta-hydroxylase, these data indicate that the catecholaminergic carotid body afferent neurons are dopaminergic. Finally, ultrastructural analysis of the peripheral processes of tyrosine hydroxylase-positive afferent terminals in the carotid body demonstrated endings in close opposition to Type I glomus cells, consistent with a role for dopaminergic afferent neurons in carotid body chemoreception. One possibility is that these cells, in addition to their role as afferents, constitute a morphologic substrate for dopaminergic \"efferent\" inhibition in the carotid body."} {"id": "PMID:1283214", "title": "A calcium-permeable channel in the apical membrane of primary cultures of the rabbit distal bright convoluted tubule.", "content": "Calcium is actively reabsorbed in the distal nephron segments and recent studies have demonstrated the presence of Ca2+ channels in these epithelial cells, which could be involved in transepithelial transport. To test this possibility, single-channel currents were recorded by the patch-clamp technique in the apical membrane of primary cultures of the rabbit distal bright convoluted tubule cells (DCTb). In the cell-attached mode with 100 mmol/l BaCl2 in the pipette and 145 mmol/l NaCl in the bath, inward negative currents, consistent with Ba2+ currents, were recorded. In these conditions, the single-channel conductance was 15 pS. In excised inside-out patches, the single-channel conductance was 13 pS and the current reversal potential of +60 mV was close to the Nernst equilibrium potential for Ba2+ (> +58 mV). Similar experiments conducted with Ca2+ as the main charge carrier showed that this ion was less permeant through the channel than Ba2+ (PBa/PCa approximately 1.4). We also showed that the Ca(2+)-channel blocker, lanthanum (1 mumol/l La3+), added on the cytosolic side of the membrane, reversibly blocked the channel activity. On the other hand, verapamil (0.1 mmol/l) and nifedipine (10 mumol/l), perfused on the cytosolic side of the membrane, abolished the channel activity but this effect was not reversible. Another type of channel was also identified in the apical membrane of cultured DCTb cells. Ion-substitution experiments showed that this 21-pS conductance channel did not discriminate between Na+ and K+ and did not conduct Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "A calcium-permeable channel in the apical membrane of primary cultures of the rabbit distal bright convoluted tubule. Calcium is actively reabsorbed in the distal nephron segments and recent studies have demonstrated the presence of Ca2+ channels in these epithelial cells, which could be involved in transepithelial transport. To test this possibility, single-channel currents were recorded by the patch-clamp technique in the apical membrane of primary cultures of the rabbit distal bright convoluted tubule cells (DCTb). In the cell-attached mode with 100 mmol/l BaCl2 in the pipette and 145 mmol/l NaCl in the bath, inward negative currents, consistent with Ba2+ currents, were recorded. In these conditions, the single-channel conductance was 15 pS. In excised inside-out patches, the single-channel conductance was 13 pS and the current reversal potential of +60 mV was close to the Nernst equilibrium potential for Ba2+ (> +58 mV). Similar experiments conducted with Ca2+ as the main charge carrier showed that this ion was less permeant through the channel than Ba2+ (PBa/PCa approximately 1.4). We also showed that the Ca(2+)-channel blocker, lanthanum (1 mumol/l La3+), added on the cytosolic side of the membrane, reversibly blocked the channel activity. On the other hand, verapamil (0.1 mmol/l) and nifedipine (10 mumol/l), perfused on the cytosolic side of the membrane, abolished the channel activity but this effect was not reversible. Another type of channel was also identified in the apical membrane of cultured DCTb cells. Ion-substitution experiments showed that this 21-pS conductance channel did not discriminate between Na+ and K+ and did not conduct Ba2+.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283215", "title": "Large-conductance chloride channels of new-born rat cardiac myocytes are activated by hypotonic media.", "content": "Large-conductance chloride (LC-type Cl-) channel activity was studied in rat ventricular myocyte membrane during development. In contrast with results previously obtained in cultured ventricular myocytes of the new-born rat, we failed to record single-channel activity in freshly isolated myocytes whatever the age of the animal (from 2 days old to adult) and the recording patch configuration used. However, spontaneous single-channel activity of LC-type Cl- channels was recorded in bleb membranes of myocytes of rats younger than 12 days, with a higher frequency in excised inside-out membrane patches than in cell-attached membrane patches. In intact neonatal myocytes, application of hypotonic media (150 mOsm) also initiated the channel activity, after variable delays (25-200 s). The channel could not be activated by suction applied through the pipette and was not observable in cells from rats older than 15 days. The LC-type Cl- channels showed properties similar to those reported in other preparations and previously observed in cardiac cultured cells: they had a large single-channel conductance of 400 pS in symmetrical 150 mM NaCl, showed multiple subconductance states, a relatively high selectivity to Cl- ions over Na+ ions (PCl/PNa = 24.6), were blocked by 10 microM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) and showed voltage-dependent inactivation. They were not activated by 10 microM colchicine or 3 microM cytochalasin D.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Large-conductance chloride channels of new-born rat cardiac myocytes are activated by hypotonic media. Large-conductance chloride (LC-type Cl-) channel activity was studied in rat ventricular myocyte membrane during development. In contrast with results previously obtained in cultured ventricular myocytes of the new-born rat, we failed to record single-channel activity in freshly isolated myocytes whatever the age of the animal (from 2 days old to adult) and the recording patch configuration used. However, spontaneous single-channel activity of LC-type Cl- channels was recorded in bleb membranes of myocytes of rats younger than 12 days, with a higher frequency in excised inside-out membrane patches than in cell-attached membrane patches. In intact neonatal myocytes, application of hypotonic media (150 mOsm) also initiated the channel activity, after variable delays (25-200 s). The channel could not be activated by suction applied through the pipette and was not observable in cells from rats older than 15 days. The LC-type Cl- channels showed properties similar to those reported in other preparations and previously observed in cardiac cultured cells: they had a large single-channel conductance of 400 pS in symmetrical 150 mM NaCl, showed multiple subconductance states, a relatively high selectivity to Cl- ions over Na+ ions (PCl/PNa = 24.6), were blocked by 10 microM 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulphonic acid (SITS) and showed voltage-dependent inactivation. They were not activated by 10 microM colchicine or 3 microM cytochalasin D.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283216", "title": "Chloride and potassium conductances of cultured human sweat ducts.", "content": "The purpose of this study was to characterize the ion conductances, in particular those for Cl- and K+, of human sweat duct cells grown in primary culture. Sweat duct cells from healthy individuals were grown to confluence on a dialysis membrane, which was then mounted in a mini-Ussing chamber and transepithelial and intracellular potentials were measured under open-circuit conditions. Under control conditions the epithelia developed mucosa-negative transepithelial potentials, Vte, of about -10 mV. The apical membrane potential, Va, was -25 mV to -30 mV (n = 97) in most cells, but several cells had a higher potential of about -55 mV (n = 29). Mucosal amiloride (10 mumol/l) hyperpolarized Va from -31 +/- 1 mV to a new sustained level of -46 +/- 2 mV (n = 36). These changes were accompanied by increase in the fractional resistance of the apical membrane, fRa, and decreases of Vte and the equivalent short-circuit current, Isc. In amiloride-treated tissues an increase in mucosal K+ concentration (5 mmol/l to 25 mmol/l) depolarized Va by 5 +/- 1 mV (n = 8), while the same step on the serosal side depolarized Va by 20 +/- 2 mV (n = 8). A Cl- channel blocker 3',5-dichlorodiphenylamine-2-carboxylate DCl-DPC; 10 mumol/l) depolarized Va by 5 +/- 1 mV (n = 6), an effect that was lost after amiloride application. The blocker had no effect from the serosal side. Reduction of mucosal Cl- (from 120 to 30 or 10 mmol/l) depolarized Va by 9-11 mV (n = 35), an effect that was often followed by a secondary hyperpolarization of 10-30 mV (n = 27).(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Chloride and potassium conductances of cultured human sweat ducts. The purpose of this study was to characterize the ion conductances, in particular those for Cl- and K+, of human sweat duct cells grown in primary culture. Sweat duct cells from healthy individuals were grown to confluence on a dialysis membrane, which was then mounted in a mini-Ussing chamber and transepithelial and intracellular potentials were measured under open-circuit conditions. Under control conditions the epithelia developed mucosa-negative transepithelial potentials, Vte, of about -10 mV. The apical membrane potential, Va, was -25 mV to -30 mV (n = 97) in most cells, but several cells had a higher potential of about -55 mV (n = 29). Mucosal amiloride (10 mumol/l) hyperpolarized Va from -31 +/- 1 mV to a new sustained level of -46 +/- 2 mV (n = 36). These changes were accompanied by increase in the fractional resistance of the apical membrane, fRa, and decreases of Vte and the equivalent short-circuit current, Isc. In amiloride-treated tissues an increase in mucosal K+ concentration (5 mmol/l to 25 mmol/l) depolarized Va by 5 +/- 1 mV (n = 8), while the same step on the serosal side depolarized Va by 20 +/- 2 mV (n = 8). A Cl- channel blocker 3',5-dichlorodiphenylamine-2-carboxylate DCl-DPC; 10 mumol/l) depolarized Va by 5 +/- 1 mV (n = 6), an effect that was lost after amiloride application. The blocker had no effect from the serosal side. Reduction of mucosal Cl- (from 120 to 30 or 10 mmol/l) depolarized Va by 9-11 mV (n = 35), an effect that was often followed by a secondary hyperpolarization of 10-30 mV (n = 27).(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283217", "title": "The outwardly rectifying Cl- channel is not involved in cAMP-mediated Cl- secretion in HT-29 cells: evidence for a very-low-conductance Cl- channel.", "content": "The patch-clamp technique and transepithelial current measurements in conjunction with analysis of transepithelial current noise were employed in order to clarify the role of the outwardly rectifying, depolarization-induced Cl- channel (ORDIC) during cAMP-mediated Cl- secretion in HT-29/B6 cells. Confluent monolayers growing on permeable supports were used in order to ensure the apical location of measured Cl- channels. The ORDIC needed to be activated by excision and/or depolarization, and was found in both cAMP-stimulated and non-stimulated cells. Both 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and 4,4'-dinitro-2,2'-stilbenedisulphonate (DNDS) induced fast flickery-type blocks of the ORDIC at low, micromolar blocker concentrations and were used as a probe for ODIC. However, these substances were ineffective in blocking transepithelial forskolin-induced Cl- secretion of monolayers in Ussing chambers. No inhibitory effect at all was detected for DNDS up to 1 mmol/l. NPPB blocked the ORDIC at low concentrations (IC50 = 0.5 +/- 0.3 mumol/l) by reducing its open probability, but NPPB did not block forskolin-induced Cl- secretion unless high concentrations were used (IC50 = 240 +/- 10 mumol/l). In order to exclude effects of NPPB other than on the apical Cl- channel, transepithelial measurements were performed in basolaterally amphotericin-permeabilized, forskolin-stimulated preparations, and a serosal-to-mucosal Cl- gradient was applied as a driving force. Under these conditions, NPPB's inhibitory effects were also very small. Noise analysis of this gradient-driven Cl- current showed a very-low-frequency Lorentzian noise component (fc = 1.4 +/- 0.2 Hz), which was not compatible with Lorentzians predicted from single-channel gating of ORDIC.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "The outwardly rectifying Cl- channel is not involved in cAMP-mediated Cl- secretion in HT-29 cells: evidence for a very-low-conductance Cl- channel. The patch-clamp technique and transepithelial current measurements in conjunction with analysis of transepithelial current noise were employed in order to clarify the role of the outwardly rectifying, depolarization-induced Cl- channel (ORDIC) during cAMP-mediated Cl- secretion in HT-29/B6 cells. Confluent monolayers growing on permeable supports were used in order to ensure the apical location of measured Cl- channels. The ORDIC needed to be activated by excision and/or depolarization, and was found in both cAMP-stimulated and non-stimulated cells. Both 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) and 4,4'-dinitro-2,2'-stilbenedisulphonate (DNDS) induced fast flickery-type blocks of the ORDIC at low, micromolar blocker concentrations and were used as a probe for ODIC. However, these substances were ineffective in blocking transepithelial forskolin-induced Cl- secretion of monolayers in Ussing chambers. No inhibitory effect at all was detected for DNDS up to 1 mmol/l. NPPB blocked the ORDIC at low concentrations (IC50 = 0.5 +/- 0.3 mumol/l) by reducing its open probability, but NPPB did not block forskolin-induced Cl- secretion unless high concentrations were used (IC50 = 240 +/- 10 mumol/l). In order to exclude effects of NPPB other than on the apical Cl- channel, transepithelial measurements were performed in basolaterally amphotericin-permeabilized, forskolin-stimulated preparations, and a serosal-to-mucosal Cl- gradient was applied as a driving force. Under these conditions, NPPB's inhibitory effects were also very small. Noise analysis of this gradient-driven Cl- current showed a very-low-frequency Lorentzian noise component (fc = 1.4 +/- 0.2 Hz), which was not compatible with Lorentzians predicted from single-channel gating of ORDIC.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283218", "title": "Cardiac gap junctions: three distinct single channel conductances and their modulation by phosphorylating treatments.", "content": "The effects of an increase in intracellular cyclic GMP (cGMP)-concentration on gap junctional current (Ij) were studied in cultured neonatal rat heart cells using both the whole-cell and perforated patch voltage-clamp method. In whole-cell measurements, exposure to 8-bromo-cGMP or carbachol reduced Ij. With the perforated patch technique, on the other hand, Ij was not affected by either 8-bromo-cGMP or carbachol. Addition of alkaline phosphatase prevented the carbachol-induced decrease in Ij in whole-cell measurements. Reduction of Ij in well-coupled cell pairs by application of heptanol allowed us to study the effects of these substances on the single gap junction channel level. We found that cGMP-treatment shifts the single channel conductance (gamma j) from 43 to 21 pS in whole-cell measurements and that intracellular addition of phosphatase prevents this shift. In contrast, intracellular phosphatase-treatment itself shifts gamma j to 70 pS. Our results indicate that Cx43-gap junction channels may exhibit three conductance levels (21 pS, 40-45 pS and 70 pS), depending on the phosphorylation state of the protein.", "contents": "Cardiac gap junctions: three distinct single channel conductances and their modulation by phosphorylating treatments. The effects of an increase in intracellular cyclic GMP (cGMP)-concentration on gap junctional current (Ij) were studied in cultured neonatal rat heart cells using both the whole-cell and perforated patch voltage-clamp method. In whole-cell measurements, exposure to 8-bromo-cGMP or carbachol reduced Ij. With the perforated patch technique, on the other hand, Ij was not affected by either 8-bromo-cGMP or carbachol. Addition of alkaline phosphatase prevented the carbachol-induced decrease in Ij in whole-cell measurements. Reduction of Ij in well-coupled cell pairs by application of heptanol allowed us to study the effects of these substances on the single gap junction channel level. We found that cGMP-treatment shifts the single channel conductance (gamma j) from 43 to 21 pS in whole-cell measurements and that intracellular addition of phosphatase prevents this shift. In contrast, intracellular phosphatase-treatment itself shifts gamma j to 70 pS. Our results indicate that Cx43-gap junction channels may exhibit three conductance levels (21 pS, 40-45 pS and 70 pS), depending on the phosphorylation state of the protein."} {"id": "PMID:1283219", "title": "Heterologous expression of the human potassium channel Kv2.1 in clonal mammalian cells by direct cytoplasmic microinjection of cRNA.", "content": "The cloned human delayed rectifying K+ channel Kv2.1 (drk1) was expressed in clonal mouse fibroblasts (L-cells) and rat basophilic leukemia cells (RBL-1) by direct cytoplasmic microinjection of complementary RNA (cRNA). Within six hours, cells microinjected with Kv2.1 cRNA expressed a large sustained outward current as determined from whole-cell patch-clamp recordings. Nearly 100% of cells injected with cRNA expressed outward current. Current density was 30-70 pA/pF when measured at a potential of +50 mV. Steady-state activation and inactivation parameters for Kv2.1 were similar when expressed in either L-cells or RBL-1 cells. These results are the first to demonstrate that functional ion channel proteins can be expressed in mammalian clonal cell lines by direct cytoplasmic microinjection of cRNA.", "contents": "Heterologous expression of the human potassium channel Kv2.1 in clonal mammalian cells by direct cytoplasmic microinjection of cRNA. The cloned human delayed rectifying K+ channel Kv2.1 (drk1) was expressed in clonal mouse fibroblasts (L-cells) and rat basophilic leukemia cells (RBL-1) by direct cytoplasmic microinjection of complementary RNA (cRNA). Within six hours, cells microinjected with Kv2.1 cRNA expressed a large sustained outward current as determined from whole-cell patch-clamp recordings. Nearly 100% of cells injected with cRNA expressed outward current. Current density was 30-70 pA/pF when measured at a potential of +50 mV. Steady-state activation and inactivation parameters for Kv2.1 were similar when expressed in either L-cells or RBL-1 cells. These results are the first to demonstrate that functional ion channel proteins can be expressed in mammalian clonal cell lines by direct cytoplasmic microinjection of cRNA."} {"id": "PMID:1283221", "title": "Mucoadhesion of copolymers and mixtures containing polyacrylic acid.", "content": "Water-soluble polymers were synthesized from dextran and polyacrylic acid and their ocular mucoadhesion was evaluated. One series had polyacrylic acid grafted onto the polysaccharide backbone of dextran, and another series had dextran grafted onto the polyacrylic acid backbone. Mucoadhesion of these copolymers was investigated using a tensile apparatus and compared with that of polyacrylic acid/dextran mixtures prepared in different proportions. Whatever the copolymer structure, no synergistic effects were seen and mucoadhesion was not markedly increased compared to dextran. The adhesion of copolymers was the same as that of mixtures having a similar polyacrylic acid content and was always less than that of polyacrylic acid alone. Formation of an interpolymer complex occurred at concentrations up to 60% polyacrylic acid, and only above this value did bioadhesion increase above that of dextran. When this complex was dissociated by neutralization of the carboxyl groups of polyacrylic acid, the mucoadhesion of the copolymers and the mixtures was improved. These experiments demonstrated that copolymers and mixtures of dextran and polyacrylic acid did not produce polymers with improved ocular mucoadhesion.", "contents": "Mucoadhesion of copolymers and mixtures containing polyacrylic acid. Water-soluble polymers were synthesized from dextran and polyacrylic acid and their ocular mucoadhesion was evaluated. One series had polyacrylic acid grafted onto the polysaccharide backbone of dextran, and another series had dextran grafted onto the polyacrylic acid backbone. Mucoadhesion of these copolymers was investigated using a tensile apparatus and compared with that of polyacrylic acid/dextran mixtures prepared in different proportions. Whatever the copolymer structure, no synergistic effects were seen and mucoadhesion was not markedly increased compared to dextran. The adhesion of copolymers was the same as that of mixtures having a similar polyacrylic acid content and was always less than that of polyacrylic acid alone. Formation of an interpolymer complex occurred at concentrations up to 60% polyacrylic acid, and only above this value did bioadhesion increase above that of dextran. When this complex was dissociated by neutralization of the carboxyl groups of polyacrylic acid, the mucoadhesion of the copolymers and the mixtures was improved. These experiments demonstrated that copolymers and mixtures of dextran and polyacrylic acid did not produce polymers with improved ocular mucoadhesion."} {"id": "PMID:1283220", "title": "[Endometriosis of the large intestine].", "content": "Two cases of large intestine endometriosis are presented. The disease was diagnosed during histological examination of samples taken during surgery. Clinically one case was diagnosed as Crohn's disease, while the second as cancer of the large intestine. The authors suggest, that an extent of surgery for, tumours of the large intestine should be carefully planned, specially if the tissue specimen was not examined histologically earlier.", "contents": "[Endometriosis of the large intestine]. Two cases of large intestine endometriosis are presented. The disease was diagnosed during histological examination of samples taken during surgery. Clinically one case was diagnosed as Crohn's disease, while the second as cancer of the large intestine. The authors suggest, that an extent of surgery for, tumours of the large intestine should be carefully planned, specially if the tissue specimen was not examined histologically earlier."} {"id": "PMID:1283223", "title": "Folate deficiency, biopterin and monoamine metabolism in depression.", "content": "Seven (21%) of 34 patients with a severe DSM-III diagnosis of major depression had red-cell folate levels below 150 ng/ml. This subgroup with folate deficiency had significantly lower CSF 5-hydroxyindoleacetic acid (5HIAA) compared to neurological controls. For all depressed patients red-cell folate was significantly correlated with CSF 5HIAA and homovanillic acid (HVA). CSF tetrahydrobiopterin (BH4) was significantly correlated with CSF 5HIAA and HVA and red-cell folate. Our observations provide further evidence of the links between folate, biopterin and monoamine metabolism in depression.", "contents": "Folate deficiency, biopterin and monoamine metabolism in depression. Seven (21%) of 34 patients with a severe DSM-III diagnosis of major depression had red-cell folate levels below 150 ng/ml. This subgroup with folate deficiency had significantly lower CSF 5-hydroxyindoleacetic acid (5HIAA) compared to neurological controls. For all depressed patients red-cell folate was significantly correlated with CSF 5HIAA and homovanillic acid (HVA). CSF tetrahydrobiopterin (BH4) was significantly correlated with CSF 5HIAA and HVA and red-cell folate. Our observations provide further evidence of the links between folate, biopterin and monoamine metabolism in depression."} {"id": "PMID:1283224", "title": "Sulfur dioxide-induced bronchoconstriction via ruthenium red-sensitive activation of sensory nerves.", "content": "The mechanism of sulfur dioxide-induced bronchoconstriction was studied using isolated perfused and ventilated guinea-pig lungs. They were exposed to sulfur dioxide after pretreatment with different compounds, either via the pulmonary artery or via the air passages. Neither the cyclooxygenase inhibitor indomethacin (30 microM) nor the H1-receptor antagonist diphenhydramine (15 microM), given via the perfusate, attenuated the sulfur dioxide-induced bronchoconstriction. Furthermore, sulfur dioxide exposure did not cause a release of either thromboxane or histamine into the perfusate. In experiments with atropine equivocal results were obtained with regard to protection against sulfur dioxide-evoked bronchoconstriction. Intratracheal instillation of the local anesthetic agent lidocaine (1 mg/50 microliters) markedly reduced the sulfur dioxide-induced bronchoconstriction. Also, ruthenium red (10 microM), an agent with calcium entry-blocking properties and an inhibitor of capsaicin-induced bronchoconstriction, was able to inhibit the effect of sulfur dioxide. The sulfur dioxide-induced bronchoconstriction was associated with release of calcitonin gene-related peptide, a sensory neuropeptide. The effect of sulfur dioxide was also inhibited by a Ca(2+)-free buffer plus EGTA. These results suggest that sulfur dioxide-induced bronchoconstriction in the guinea-pig lung is the result of a local effect on sensory nerves (C-fiber activation). The mechanism seems to be dependent on the Ca(2+)-dependent release of sensory neuropeptides and to be linked to opening of the cation channel, which is associated with the proposed capsaicin receptor on sensory nerves as revealed by the inhibitory effect of ruthenium red.", "contents": "Sulfur dioxide-induced bronchoconstriction via ruthenium red-sensitive activation of sensory nerves. The mechanism of sulfur dioxide-induced bronchoconstriction was studied using isolated perfused and ventilated guinea-pig lungs. They were exposed to sulfur dioxide after pretreatment with different compounds, either via the pulmonary artery or via the air passages. Neither the cyclooxygenase inhibitor indomethacin (30 microM) nor the H1-receptor antagonist diphenhydramine (15 microM), given via the perfusate, attenuated the sulfur dioxide-induced bronchoconstriction. Furthermore, sulfur dioxide exposure did not cause a release of either thromboxane or histamine into the perfusate. In experiments with atropine equivocal results were obtained with regard to protection against sulfur dioxide-evoked bronchoconstriction. Intratracheal instillation of the local anesthetic agent lidocaine (1 mg/50 microliters) markedly reduced the sulfur dioxide-induced bronchoconstriction. Also, ruthenium red (10 microM), an agent with calcium entry-blocking properties and an inhibitor of capsaicin-induced bronchoconstriction, was able to inhibit the effect of sulfur dioxide. The sulfur dioxide-induced bronchoconstriction was associated with release of calcitonin gene-related peptide, a sensory neuropeptide. The effect of sulfur dioxide was also inhibited by a Ca(2+)-free buffer plus EGTA. These results suggest that sulfur dioxide-induced bronchoconstriction in the guinea-pig lung is the result of a local effect on sensory nerves (C-fiber activation). The mechanism seems to be dependent on the Ca(2+)-dependent release of sensory neuropeptides and to be linked to opening of the cation channel, which is associated with the proposed capsaicin receptor on sensory nerves as revealed by the inhibitory effect of ruthenium red."} {"id": "PMID:1283225", "title": "[The role of radiotherapy in the early stages of Hodgkin's disease].", "content": "The outcome of treatment for a first relapse in early stages (IA and IIA) of Hodgkin's disease after primary radiotherapy was analyzed in 86 patients. They received total nodal radiotherapy (TNR) as the primary treatment. Survival was used as the major endpoint. Median follow-up was 13.1 years. Duration of first complete remission was 60% for patients in stage IA and 39% for patients in stage IIA (p < .01). At 10-years, the survival for patients in stage IA was 78% and only 55% for patients in stage IIA (p < .01). A risk factor analysis showed that the presence of stage IIA and bulky disease (adenopathy > 7 cm) were associated with a worse prognosis. We believe that the use of TNR as initial treatment in early stages of Hodgkin's disease should be considered in patients in stage IA and without bulky disease. Patients in stage IIA and risk factors, such as bulky disease, should be treated with more aggressive therapeutic regimens.", "contents": "[The role of radiotherapy in the early stages of Hodgkin's disease]. The outcome of treatment for a first relapse in early stages (IA and IIA) of Hodgkin's disease after primary radiotherapy was analyzed in 86 patients. They received total nodal radiotherapy (TNR) as the primary treatment. Survival was used as the major endpoint. Median follow-up was 13.1 years. Duration of first complete remission was 60% for patients in stage IA and 39% for patients in stage IIA (p < .01). At 10-years, the survival for patients in stage IA was 78% and only 55% for patients in stage IIA (p < .01). A risk factor analysis showed that the presence of stage IIA and bulky disease (adenopathy > 7 cm) were associated with a worse prognosis. We believe that the use of TNR as initial treatment in early stages of Hodgkin's disease should be considered in patients in stage IA and without bulky disease. Patients in stage IIA and risk factors, such as bulky disease, should be treated with more aggressive therapeutic regimens."} {"id": "PMID:1283226", "title": "Follicular gastritis and its association with Helicobacter pylori infection.", "content": "Fifty endoscopic biopsies with follicular gastritis (FG) were reviewed to define the frequency of association of FG and Helicobacter pylori (H pylori) infection. All biopsies were studied in sections stained with hematoxylin and eosin and no special techniques were employed. In forty-two out of the fifty cases (84%) H pylori was documented and most of the gastritis showed activity. There was no correlation between the quantity of follicles and the number of bacilli; some biopsies with few follicles showed many microorganisms and others with many follicles showed only a few. There was also no correlation between the presence of the follicles and the distribution of Helicobacter: in some biopsies the microorganisms were found in the tissue fragments with hyperplastic follicles but in others, it was observed in fragments without lymphoid follicles. The high frequency of association between FG and H pylori suggests that this microorganism has some antigenic properties that condition lymphoid tissue hyperplasia in gastric mucosa. It is concluded that the diagnosis of follicular gastritis should be considered an important finding and its presence should lead to a careful search for H pylori. In most cases the microorganism can be identified in routine sections using only hematoxylin and eosin stain.", "contents": "Follicular gastritis and its association with Helicobacter pylori infection. Fifty endoscopic biopsies with follicular gastritis (FG) were reviewed to define the frequency of association of FG and Helicobacter pylori (H pylori) infection. All biopsies were studied in sections stained with hematoxylin and eosin and no special techniques were employed. In forty-two out of the fifty cases (84%) H pylori was documented and most of the gastritis showed activity. There was no correlation between the quantity of follicles and the number of bacilli; some biopsies with few follicles showed many microorganisms and others with many follicles showed only a few. There was also no correlation between the presence of the follicles and the distribution of Helicobacter: in some biopsies the microorganisms were found in the tissue fragments with hyperplastic follicles but in others, it was observed in fragments without lymphoid follicles. The high frequency of association between FG and H pylori suggests that this microorganism has some antigenic properties that condition lymphoid tissue hyperplasia in gastric mucosa. It is concluded that the diagnosis of follicular gastritis should be considered an important finding and its presence should lead to a careful search for H pylori. In most cases the microorganism can be identified in routine sections using only hematoxylin and eosin stain."} {"id": "PMID:1283230", "title": "Response of lipoprotein lipase to calorie intake in streptozotocin-induced diabetic rats.", "content": "The mechanism regulating lipoprotein lipase (LPL) expression in adipose tissue was examined in rats in the conditions of different calorie intakes with and without streptozotocin-induced (STZ-) diabetes. The LPL activity released from adipose tissue was greater with the higher calorie intake (20 g of normal chow diet per day) than with the lower calorie intake (13 g of normal chow diet per day), and was greater in normal rats than in STZ-diabetic rats. The LPL activity was proportional to the serum insulin level in all conditions. Dot-blot analysis showed that the amount of LPL mRNA in adipose tissue was increased by the higher calorie diet and that the increase was less in the diabetic state. Expression of mRNA was also nearly parallel with the serum insulin level. LPL activity released from the heart was not affected by either the calorie intake or the diabetic state. These results suggest that the mechanisms of LPL expression in adipose tissue and the heart are different, and that LPL expression in adipose tissue was closely dependent on the insulin level.", "contents": "Response of lipoprotein lipase to calorie intake in streptozotocin-induced diabetic rats. The mechanism regulating lipoprotein lipase (LPL) expression in adipose tissue was examined in rats in the conditions of different calorie intakes with and without streptozotocin-induced (STZ-) diabetes. The LPL activity released from adipose tissue was greater with the higher calorie intake (20 g of normal chow diet per day) than with the lower calorie intake (13 g of normal chow diet per day), and was greater in normal rats than in STZ-diabetic rats. The LPL activity was proportional to the serum insulin level in all conditions. Dot-blot analysis showed that the amount of LPL mRNA in adipose tissue was increased by the higher calorie diet and that the increase was less in the diabetic state. Expression of mRNA was also nearly parallel with the serum insulin level. LPL activity released from the heart was not affected by either the calorie intake or the diabetic state. These results suggest that the mechanisms of LPL expression in adipose tissue and the heart are different, and that LPL expression in adipose tissue was closely dependent on the insulin level."} {"id": "PMID:1283227", "title": "Primary B cell lymphoma of the rectum in a patient coinfected with HIV-1 and HTLV-I.", "content": "This report describes a clinical case of a large cell, immunoblastic plasmacytoid malignant B-cell lymphoma of the rectum in an AIDS patient coinfected with HTLV-I. The malignant cells showed clonal genetic rearrangement of the HC (JH) and LCK genes. Infection by EBV was demonstrated serologically and with slot blots using genomic DNA of the cancer cells. Southern blot analysis with DNA extracted from the lymphoma cells were negative for HTLV-I. The patient received seven cycles of VACO-B which induced complete but transient clinical remission of the tumor. The final outcome of the patient is unknown.", "contents": "Primary B cell lymphoma of the rectum in a patient coinfected with HIV-1 and HTLV-I. This report describes a clinical case of a large cell, immunoblastic plasmacytoid malignant B-cell lymphoma of the rectum in an AIDS patient coinfected with HTLV-I. The malignant cells showed clonal genetic rearrangement of the HC (JH) and LCK genes. Infection by EBV was demonstrated serologically and with slot blots using genomic DNA of the cancer cells. Southern blot analysis with DNA extracted from the lymphoma cells were negative for HTLV-I. The patient received seven cycles of VACO-B which induced complete but transient clinical remission of the tumor. The final outcome of the patient is unknown."} {"id": "PMID:1283228", "title": "[Non-Hodgkin's lymphoma secondary to Hodgkin's disease treated with chemo- and radiotherapy. Report of a case].", "content": "In 18 years of experience in the use of combined chemotherapy in Hodgkin's disease at the Instituto Nacional de la Nutrici\u00f3n Salvador Zubir\u00e1n, the first case of non-Hodgkin's lymphoma secondary to Hodgkin's disease was identified. The patient was a 23 year old male who initially developed a nodular sclerosis type of Hodgkin's disease. Three years later, the biopsies showed lymphocyte predominance type of Hodgkin's disease. Finally, one year later, the patient developed a diffuse small cleaved cell lymphoma. Non-Hodgkin's lymphoma occurring in patients treated with combined chemotherapy and radiotherapy after Hodgkin's disease is a rare complication. We believe that the genesis of a second neoplasm in these cases may be due to both disturbances in the cellular immunity intrinsic to Hodgkin's disease and the treatment with combined chemotherapy and radiotherapy.", "contents": "[Non-Hodgkin's lymphoma secondary to Hodgkin's disease treated with chemo- and radiotherapy. Report of a case]. In 18 years of experience in the use of combined chemotherapy in Hodgkin's disease at the Instituto Nacional de la Nutrici\u00f3n Salvador Zubir\u00e1n, the first case of non-Hodgkin's lymphoma secondary to Hodgkin's disease was identified. The patient was a 23 year old male who initially developed a nodular sclerosis type of Hodgkin's disease. Three years later, the biopsies showed lymphocyte predominance type of Hodgkin's disease. Finally, one year later, the patient developed a diffuse small cleaved cell lymphoma. Non-Hodgkin's lymphoma occurring in patients treated with combined chemotherapy and radiotherapy after Hodgkin's disease is a rare complication. We believe that the genesis of a second neoplasm in these cases may be due to both disturbances in the cellular immunity intrinsic to Hodgkin's disease and the treatment with combined chemotherapy and radiotherapy."} {"id": "PMID:1283232", "title": "Influence of agents affecting monooxygenase activity on taurolithocholic acid-induced cholestasis.", "content": "In rats, pretreatment with certain ketones results in enhanced taurolithocholic acid (TLCA)-induced reduction in bile flow, whereas pretreatment with inhibitors of protein synthesis diminishes the effect on bile flow of cholestatic regimens. In the present study, the possible role of cytochrome P-450 in the ketone potentiation phenomenon was investigated. Male rats were pretreated with inducers or inhibitors of hepatic cytochrome P-450 and the impact of these pretreatments on TLCA-induced cholestasis assessed. Phenobarbital, 3-methylcholanthrene, chlordecone or mirex were used as inducers, and SKF 525-A, piperonyl butoxide, or cobaltous chloride as inhibitors of monooxygenase activity. Phenobarbital and 3-methylcholanthrene pretreatment enhanced TLCA-induced reduction of bile flow, while mirex and chlordecone were without effect. The three inhibitors of monooxygenase activity did not diminish TLCA-induced cholestasis. Instead, piperonyl butoxide and cobaltous chloride appeared to enhance the action of TLCA. Consequently, an increase in cytochrome P-450 (or specific isozymes) as a common denominator in the potentiation phenomenon appears unlikely. While hepatic proteins may play an important role in the potentiation of TLCA-induced cholestasis following pretreatment with ketones, the pattern of potentiation after pretreatment of rats with different inducers or inhibitors of cytochrome P-450 does not appear to implicate this family of proteins.", "contents": "Influence of agents affecting monooxygenase activity on taurolithocholic acid-induced cholestasis. In rats, pretreatment with certain ketones results in enhanced taurolithocholic acid (TLCA)-induced reduction in bile flow, whereas pretreatment with inhibitors of protein synthesis diminishes the effect on bile flow of cholestatic regimens. In the present study, the possible role of cytochrome P-450 in the ketone potentiation phenomenon was investigated. Male rats were pretreated with inducers or inhibitors of hepatic cytochrome P-450 and the impact of these pretreatments on TLCA-induced cholestasis assessed. Phenobarbital, 3-methylcholanthrene, chlordecone or mirex were used as inducers, and SKF 525-A, piperonyl butoxide, or cobaltous chloride as inhibitors of monooxygenase activity. Phenobarbital and 3-methylcholanthrene pretreatment enhanced TLCA-induced reduction of bile flow, while mirex and chlordecone were without effect. The three inhibitors of monooxygenase activity did not diminish TLCA-induced cholestasis. Instead, piperonyl butoxide and cobaltous chloride appeared to enhance the action of TLCA. Consequently, an increase in cytochrome P-450 (or specific isozymes) as a common denominator in the potentiation phenomenon appears unlikely. While hepatic proteins may play an important role in the potentiation of TLCA-induced cholestasis following pretreatment with ketones, the pattern of potentiation after pretreatment of rats with different inducers or inhibitors of cytochrome P-450 does not appear to implicate this family of proteins."} {"id": "PMID:1283233", "title": "Fetal mouse salivary glands and applications for determining teratogenic mechanisms in vitro.", "content": "Culture systems offer advantages for studying the actions of chemicals on mechanisms of development. Growth, [3H]thymidine incorporation, and 14C-amino acid incorporation were measured to determine culture conditions and the response of glands to three chemicals. Eagle's MEM supported the best growth and the best time for double isotope presence was the second 24 h of culture. Cyclamate had no effect on growth or isotope incorporation but cycloheximide disturbed 14C more than 3H. 5-Azacytidine was toxic but the incorporation of both isotopes exhibited the same pattern.", "contents": "Fetal mouse salivary glands and applications for determining teratogenic mechanisms in vitro. Culture systems offer advantages for studying the actions of chemicals on mechanisms of development. Growth, [3H]thymidine incorporation, and 14C-amino acid incorporation were measured to determine culture conditions and the response of glands to three chemicals. Eagle's MEM supported the best growth and the best time for double isotope presence was the second 24 h of culture. Cyclamate had no effect on growth or isotope incorporation but cycloheximide disturbed 14C more than 3H. 5-Azacytidine was toxic but the incorporation of both isotopes exhibited the same pattern."} {"id": "PMID:1283234", "title": "[Diagnostic value of the analysis of alpha fetoprotein levels in malignant neoplasms of the digestive system].", "content": "The concentration of alpha-fetoprotein (AFP) in serum was determined in 58 patients (35 males and 23 females) aged from 38 to 87 years treated surgically for malignant tumours of the digestive tract, including colonic carcinoma in 30, gastric carcinoma in 11, pancreatic carcinoma in 10 and oesophageal carcinoma in 7 cases. In 33 patients the tumour was disseminated (into the liver in 22 cases). On the ground of AFP concentration determinations in 40 patients (19 males and 21 females) aged 22 to 80 years operated on for non-neoplastic abdominal diseases the upper normal range was accepted as 9.42 ng/ml. Raised AFP concentration was found in only patient with advanced pancreatic carcinoma and multiple metastases to the liver and lymph nodes. The study showed that serum AFP level in cases of digestive tract malignancies is of limited diagnostic value.", "contents": "[Diagnostic value of the analysis of alpha fetoprotein levels in malignant neoplasms of the digestive system]. The concentration of alpha-fetoprotein (AFP) in serum was determined in 58 patients (35 males and 23 females) aged from 38 to 87 years treated surgically for malignant tumours of the digestive tract, including colonic carcinoma in 30, gastric carcinoma in 11, pancreatic carcinoma in 10 and oesophageal carcinoma in 7 cases. In 33 patients the tumour was disseminated (into the liver in 22 cases). On the ground of AFP concentration determinations in 40 patients (19 males and 21 females) aged 22 to 80 years operated on for non-neoplastic abdominal diseases the upper normal range was accepted as 9.42 ng/ml. Raised AFP concentration was found in only patient with advanced pancreatic carcinoma and multiple metastases to the liver and lymph nodes. The study showed that serum AFP level in cases of digestive tract malignancies is of limited diagnostic value."} {"id": "PMID:1283235", "title": "[Spontaneous intraperitoneal rupture of asymptomatic hydronephrosis].", "content": "A 63-year-old patient had spontaneous rupture of asymptomatic hydronephrosis+ into the peritoneal cavity as result of cast renal calculus. During the operation similar changes in the right kidney were found and, in view of this, palliative operation was done with removal of concrements and sparing of both pathologically changed kidneys. After the operation the kidneys resumed their function.", "contents": "[Spontaneous intraperitoneal rupture of asymptomatic hydronephrosis]. A 63-year-old patient had spontaneous rupture of asymptomatic hydronephrosis+ into the peritoneal cavity as result of cast renal calculus. During the operation similar changes in the right kidney were found and, in view of this, palliative operation was done with removal of concrements and sparing of both pathologically changed kidneys. After the operation the kidneys resumed their function."} {"id": "PMID:1283238", "title": "[Non-Hodgkin's lymphomas: principles and application of the Kiel classification].", "content": "In the Kiel classification malignant non-Hodgkin's lymphomas (NHL) are defined essentially according to their constituent cells, based on their morphologically and immunologically defined normal equivalents. For pragmatic reasons they are also divided into low and high grade malignant lymphomas. The most important condition for applying the classification is technical excellence, especially in embedding. The usual criteria of malignancy are only partially applicable to the division into reactive and malignant lymph node diseases. There are borderline cases between nonneoplastic and neoplastic lymph node diseases that cannot presently be distinguished with certainty with any method--including immunohistochemistry and molecular and classical genetics. Thus the gold standard of lymphoma diagnostics remains the subtle morphological investigation. In doubtful cases there should be close feedback between pathologists and clinicians.", "contents": "[Non-Hodgkin's lymphomas: principles and application of the Kiel classification]. In the Kiel classification malignant non-Hodgkin's lymphomas (NHL) are defined essentially according to their constituent cells, based on their morphologically and immunologically defined normal equivalents. For pragmatic reasons they are also divided into low and high grade malignant lymphomas. The most important condition for applying the classification is technical excellence, especially in embedding. The usual criteria of malignancy are only partially applicable to the division into reactive and malignant lymph node diseases. There are borderline cases between nonneoplastic and neoplastic lymph node diseases that cannot presently be distinguished with certainty with any method--including immunohistochemistry and molecular and classical genetics. Thus the gold standard of lymphoma diagnostics remains the subtle morphological investigation. In doubtful cases there should be close feedback between pathologists and clinicians."} {"id": "PMID:1283239", "title": "[Histological classification of malignant non-Hodgkin's lymphomas and patient survival: the Kiel classification versus the working formulation].", "content": "In 163 out of 251 histologically classified malignant Non-Hodgkin's lymphomas, a comparison was made of the patient survival with respect to both histological type and malignant grade according to the Kiel Classification (KC) and the three prognostic groups of the Working Formulation (WF). As expected, the survival rate of 94 low-grade malignant lymphoma cases (KC) was significantly better than that of 69 high-grade cases (p < 0.0001). Similar results were found both for 46 low grade cases (WF) in comparison to 50 high grade cases (p < 0.001) and for 67 intermediate grade cases (WF) compared with the 50 high grade cases (p < 0.05). The survival rates of low and intermediate grade cases (WF), however, showed no statistically significant difference. The low- and high-grade malignant lymphoma entities of KC, which together constitute the intermediate grade of WF, differed significantly with respect to patient survival (p < 0.05). Therefore, it appears that an intermediate grade is not essential in the KC.", "contents": "[Histological classification of malignant non-Hodgkin's lymphomas and patient survival: the Kiel classification versus the working formulation]. In 163 out of 251 histologically classified malignant Non-Hodgkin's lymphomas, a comparison was made of the patient survival with respect to both histological type and malignant grade according to the Kiel Classification (KC) and the three prognostic groups of the Working Formulation (WF). As expected, the survival rate of 94 low-grade malignant lymphoma cases (KC) was significantly better than that of 69 high-grade cases (p < 0.0001). Similar results were found both for 46 low grade cases (WF) in comparison to 50 high grade cases (p < 0.001) and for 67 intermediate grade cases (WF) compared with the 50 high grade cases (p < 0.05). The survival rates of low and intermediate grade cases (WF), however, showed no statistically significant difference. The low- and high-grade malignant lymphoma entities of KC, which together constitute the intermediate grade of WF, differed significantly with respect to patient survival (p < 0.05). Therefore, it appears that an intermediate grade is not essential in the KC."} {"id": "PMID:1283240", "title": "[Angioimmunoblastic lymphadenopathy (AILD): histology and survival time].", "content": "In order to identify histological and immunohistochemical criteria of prognostic value in AILD 40 lymph nodes with typical and 15 cases with incomplete features were semiquantitatively analyzed. Their expression were correlated with survival data of all patients. Significant prognostic value could be detected for following parameters: mitoses, immunoblasts, CD 30-positive blasts, multinuclear tumor cells and eosinophilic granulocytes. However residual lymph node structures, venules, PAS-positive material, and reticulum cells did not correlate with survival data. The short median survival time does not justify AILD grouping as low grade malignant lymphoma.", "contents": "[Angioimmunoblastic lymphadenopathy (AILD): histology and survival time]. In order to identify histological and immunohistochemical criteria of prognostic value in AILD 40 lymph nodes with typical and 15 cases with incomplete features were semiquantitatively analyzed. Their expression were correlated with survival data of all patients. Significant prognostic value could be detected for following parameters: mitoses, immunoblasts, CD 30-positive blasts, multinuclear tumor cells and eosinophilic granulocytes. However residual lymph node structures, venules, PAS-positive material, and reticulum cells did not correlate with survival data. The short median survival time does not justify AILD grouping as low grade malignant lymphoma."} {"id": "PMID:1283241", "title": "[T-cell rich B-cell lymphoma associated with hemophagocytic syndrome].", "content": "Report of a T-cell rich B-cell lymphoma (TCRBCL) in a 43 years old man with an associated haemophagocytic syndrome (HS). At presentation the haemophagocytic cells involved the same organs as the lymphoma, i.e. spleen, liver, abdominal lymph nodes and bone marrow. As supportive measure to alleviate chemotherapy-induced granulocytopenia the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was given. After an initial improvement of the blood granulocyte count pancytopenia developed again, resulting in fatal sepsis. Autopsy demonstrated massive proliferation of macrophages in the bone marrow with haemophagocytosis as morphological correlation to the pancytopenia. The observation that exogenous GM-CSF enhanced the preexistent HS primarily reactive to the TCRBCL raises the question if endogenous GM-CSF may play a role in triggering a HS. The observed association of TCRBCL and HS has not been reported so far.", "contents": "[T-cell rich B-cell lymphoma associated with hemophagocytic syndrome]. Report of a T-cell rich B-cell lymphoma (TCRBCL) in a 43 years old man with an associated haemophagocytic syndrome (HS). At presentation the haemophagocytic cells involved the same organs as the lymphoma, i.e. spleen, liver, abdominal lymph nodes and bone marrow. As supportive measure to alleviate chemotherapy-induced granulocytopenia the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) was given. After an initial improvement of the blood granulocyte count pancytopenia developed again, resulting in fatal sepsis. Autopsy demonstrated massive proliferation of macrophages in the bone marrow with haemophagocytosis as morphological correlation to the pancytopenia. The observation that exogenous GM-CSF enhanced the preexistent HS primarily reactive to the TCRBCL raises the question if endogenous GM-CSF may play a role in triggering a HS. The observed association of TCRBCL and HS has not been reported so far."} {"id": "PMID:1283242", "title": "[Lymphoid follicles of the human large bowel mucosa: structure and function].", "content": "Little is known about morphology and function of human solitary lymphoid follicles (LF), a component of the gut-associated lymphoid tissue. We have studied 156 LF in situ from 10 colorectal resection specimens by use of serial frozen sections and immunohistochemistry (APAAP technique) and found 8 to 10 LF per cm2, i.e. 11,000 to 14,000 LF in the whole organ. Two types were identified: (1) One type, located in the colon, displayed a pit-like follicle-associated epithelium (FAE). A large part of this LF extended into the submucosa. (2) The other type was noticed mainly in the tunica mucosa of the rectum and had a flat FAE. All LF exhibited a rather constant structure. The main elements were FAE, dome region, B-lymphocyte region with surrounding T-lymphocyte area including high endothelial venules, and a lymph sinus that delimited the LF against the submucosa. One out of five LF contained a germinal center. Marked differences were found between the immunological effector cell population of the LF and that of the lamina propria. These observations denote (1) a striking compartmentation of these cells in the gut mucosa; (2) a marked similarity of the immunomorphology of LF to that of Peyer patches; (3) a functional analogy: The LF belong to a physically discrete compartment that constitutes the afferent limb of the local immune system, as the Peyer patch does. The lymphomonocytic elements of the lamina propria belong to the efferent limb. Results of in vitro studies, generally based on a mixture of cells from both compartments, may thus not reflect the conditions found in vivo.", "contents": "[Lymphoid follicles of the human large bowel mucosa: structure and function]. Little is known about morphology and function of human solitary lymphoid follicles (LF), a component of the gut-associated lymphoid tissue. We have studied 156 LF in situ from 10 colorectal resection specimens by use of serial frozen sections and immunohistochemistry (APAAP technique) and found 8 to 10 LF per cm2, i.e. 11,000 to 14,000 LF in the whole organ. Two types were identified: (1) One type, located in the colon, displayed a pit-like follicle-associated epithelium (FAE). A large part of this LF extended into the submucosa. (2) The other type was noticed mainly in the tunica mucosa of the rectum and had a flat FAE. All LF exhibited a rather constant structure. The main elements were FAE, dome region, B-lymphocyte region with surrounding T-lymphocyte area including high endothelial venules, and a lymph sinus that delimited the LF against the submucosa. One out of five LF contained a germinal center. Marked differences were found between the immunological effector cell population of the LF and that of the lamina propria. These observations denote (1) a striking compartmentation of these cells in the gut mucosa; (2) a marked similarity of the immunomorphology of LF to that of Peyer patches; (3) a functional analogy: The LF belong to a physically discrete compartment that constitutes the afferent limb of the local immune system, as the Peyer patch does. The lymphomonocytic elements of the lamina propria belong to the efferent limb. Results of in vitro studies, generally based on a mixture of cells from both compartments, may thus not reflect the conditions found in vivo."} {"id": "PMID:1283243", "title": "[Morphological changes in the lymphatic system of children with hereditary immunologic deficiency syndromes].", "content": "The morphology of lymphatic tissues in 43 autopsy cases of children with inherited immunodeficiency states were analysed. Among the more common diseases, such as Di-George-syndrome, CID-patients, congenital agammaglobulinemia Bruton, CVID, selective IG-A deficiency, Wiskott-Aldrich-syndrome, tissue sections of very rare conditions associated with immunodeficiency, e.g. fetopathia diabetica and leprechaunismus, were investigated by routine and immunohistochemical stainings. Clinical history and laboratory data, augmented by the characteristic pathomorphology of lymphatic tissue sections, will establish or at least suggest a definite diagnosis. Since true thymic dysplasia is very rare (or even non-existent) in the human, this term should be abandoned. Severe thymic tissue alterations in SCID-patients, occur secondary to enzyme defects in lymphatic cells. If patients are successfully treated by bone marrow transplantation, the thymus will subsequently develop into a functionally normal organ.", "contents": "[Morphological changes in the lymphatic system of children with hereditary immunologic deficiency syndromes]. The morphology of lymphatic tissues in 43 autopsy cases of children with inherited immunodeficiency states were analysed. Among the more common diseases, such as Di-George-syndrome, CID-patients, congenital agammaglobulinemia Bruton, CVID, selective IG-A deficiency, Wiskott-Aldrich-syndrome, tissue sections of very rare conditions associated with immunodeficiency, e.g. fetopathia diabetica and leprechaunismus, were investigated by routine and immunohistochemical stainings. Clinical history and laboratory data, augmented by the characteristic pathomorphology of lymphatic tissue sections, will establish or at least suggest a definite diagnosis. Since true thymic dysplasia is very rare (or even non-existent) in the human, this term should be abandoned. Severe thymic tissue alterations in SCID-patients, occur secondary to enzyme defects in lymphatic cells. If patients are successfully treated by bone marrow transplantation, the thymus will subsequently develop into a functionally normal organ."} {"id": "PMID:1283244", "title": "[Value of \"non-specific\" lymphoid infiltrates in bone marrow in high grade malignant peripheral non-Hodgkin's lymphomas].", "content": "We studied iliac crest biopsies of 120 patients with extramedullary high-grade Non-Hodgkin's lymphomas (NHL). The bone marrow of 69 patients contained foci of small lymphoid cells, which cytologically differed significantly from the extramedullary NHL and which we termed abnormal lymphoid infiltrates (ALI). The ALIs in 14 out of 25 cases immunohistochemically investigated in more detail were made up of small CD3+ cells optionally intermingled with a minority of CD20+ cells of small to intermediate size. In 10 patients, however, the ALIs satisfied the criteria of a low-grade NHL. In the vicinity of the extramedullary high-grade lymphoma, residues of the corresponding low-grade NHL were identified in up to 7 of 10 cases. We conclude that bone marrow ALIs associated with extramedullary high-grade NHL exhibit at least in part the criteria of a systemic clonal expansion of premalignant lymphoid cells or low-grade NHLs respectively, which gives rise to the final evolution of the extramedullary high-grade NHL.", "contents": "[Value of \"non-specific\" lymphoid infiltrates in bone marrow in high grade malignant peripheral non-Hodgkin's lymphomas]. We studied iliac crest biopsies of 120 patients with extramedullary high-grade Non-Hodgkin's lymphomas (NHL). The bone marrow of 69 patients contained foci of small lymphoid cells, which cytologically differed significantly from the extramedullary NHL and which we termed abnormal lymphoid infiltrates (ALI). The ALIs in 14 out of 25 cases immunohistochemically investigated in more detail were made up of small CD3+ cells optionally intermingled with a minority of CD20+ cells of small to intermediate size. In 10 patients, however, the ALIs satisfied the criteria of a low-grade NHL. In the vicinity of the extramedullary high-grade lymphoma, residues of the corresponding low-grade NHL were identified in up to 7 of 10 cases. We conclude that bone marrow ALIs associated with extramedullary high-grade NHL exhibit at least in part the criteria of a systemic clonal expansion of premalignant lymphoid cells or low-grade NHLs respectively, which gives rise to the final evolution of the extramedullary high-grade NHL."} {"id": "PMID:1283245", "title": "Extranodal lymphomas: the MALT concept.", "content": "Extranodal lymphomas account for as many as 40% of non-Hodgkin's lymphomas and most arise in the gastro-intestinal tract which is a major lymphoid organ in its own right. Gastrointestinal (gut) associated lymphoid tissue (GALT) and that of other mucosae (MALT), differs both structurally and functionally from nodal lymphoid tissue and low grade B cell lymphomas arising in the gastrointestinal tract and other mucosae have been found to recapitulate the structure and cytological features of MALT. Moreover, these lymphomas are clinically indolent which could be explained by the restricted homing patterns of MALT. Curiously, however, most MALT lymphomas arise in sites, such as the stomach, where MALT is not normally present. Several chronic inflammatory conditions, most of which have an autoimmune component, result in the acquisition of MALT-like lymphoid tissue, and have been identified as necessary precursors for the development of MALT lymphoma. These include Helicobacter pylori induced chronic gastritis, Sj\u00f6gren's syndrome and Hashimoto's thyroiditis. Histologically, low grade MALT lymphomas are characterized by centrocyte-like (CCL) B cells which surround reactive follicles and form characteristic lympho-epithelial lesions with adjacent epithelium; they frequently show plasma cell differentiation. Specific colonization of reactive follicles by CCL cells often occurs and transformation into a high grade lymphoma may occur. The phenotype of MALT lymphoma CCL-cells is similar to that of marginal zone B cells; no characteristic genotypic features have yet been identified. When lymph nodes are involved by MALT lymphoma their appearance may be indistinguishable from those of so-called monocytid B cell lymphoma, a primary lymph node tumour which, unlike MALT lymphoma, shares the clinical features of other low grade nodal B cell lymphomas.", "contents": "Extranodal lymphomas: the MALT concept. Extranodal lymphomas account for as many as 40% of non-Hodgkin's lymphomas and most arise in the gastro-intestinal tract which is a major lymphoid organ in its own right. Gastrointestinal (gut) associated lymphoid tissue (GALT) and that of other mucosae (MALT), differs both structurally and functionally from nodal lymphoid tissue and low grade B cell lymphomas arising in the gastrointestinal tract and other mucosae have been found to recapitulate the structure and cytological features of MALT. Moreover, these lymphomas are clinically indolent which could be explained by the restricted homing patterns of MALT. Curiously, however, most MALT lymphomas arise in sites, such as the stomach, where MALT is not normally present. Several chronic inflammatory conditions, most of which have an autoimmune component, result in the acquisition of MALT-like lymphoid tissue, and have been identified as necessary precursors for the development of MALT lymphoma. These include Helicobacter pylori induced chronic gastritis, Sj\u00f6gren's syndrome and Hashimoto's thyroiditis. Histologically, low grade MALT lymphomas are characterized by centrocyte-like (CCL) B cells which surround reactive follicles and form characteristic lympho-epithelial lesions with adjacent epithelium; they frequently show plasma cell differentiation. Specific colonization of reactive follicles by CCL cells often occurs and transformation into a high grade lymphoma may occur. The phenotype of MALT lymphoma CCL-cells is similar to that of marginal zone B cells; no characteristic genotypic features have yet been identified. When lymph nodes are involved by MALT lymphoma their appearance may be indistinguishable from those of so-called monocytid B cell lymphoma, a primary lymph node tumour which, unlike MALT lymphoma, shares the clinical features of other low grade nodal B cell lymphomas."} {"id": "PMID:1283246", "title": "[Malignant lymphomas of soft tissues].", "content": "Among annually 1000 consultation cases of soft tissue tumors, minimally 1.2% to maximally 2% malignant lymphomas could be identified, which presented as (primary) soft tissues tumor. Thus malignant lymphoma as soft tissue tumor is rare, however, it has to be considered in differential diagnosis not only of cellular round cell sarcoma, but also with undifferentiated carcinomas (large cell Ki-1 lymphomas) and various myxoid spindle cell sarcomas (sarcomatoid lymphoma). Decisive in differential diagnosis were decorations with pan-leucocyte antibody, as well as, B- and T-cell markers. All cases turned out to be non-Hodgkin lymphomas, the majority of B-cell type, with large cells which qualified as centroblasts (according to Kiel classification). Similar findings, predominance of B-cell non-Hodgkin lymphomas with large cells, were reported in the few series published of malignant lymphomas as soft tissue tumors. Remarkable were relatively good prognosis with \"highly malignant\" morphology and preference for involvement of soft tissue even after dissemination. Future studies are requested to shed light on possible specific cellular findings as to phenotype and genotype in malignant lymphoma presenting as soft tissue tumors, as already had been done with subcutaneous T-cell lymphoma and primary lymphoma of the bone.", "contents": "[Malignant lymphomas of soft tissues]. Among annually 1000 consultation cases of soft tissue tumors, minimally 1.2% to maximally 2% malignant lymphomas could be identified, which presented as (primary) soft tissues tumor. Thus malignant lymphoma as soft tissue tumor is rare, however, it has to be considered in differential diagnosis not only of cellular round cell sarcoma, but also with undifferentiated carcinomas (large cell Ki-1 lymphomas) and various myxoid spindle cell sarcomas (sarcomatoid lymphoma). Decisive in differential diagnosis were decorations with pan-leucocyte antibody, as well as, B- and T-cell markers. All cases turned out to be non-Hodgkin lymphomas, the majority of B-cell type, with large cells which qualified as centroblasts (according to Kiel classification). Similar findings, predominance of B-cell non-Hodgkin lymphomas with large cells, were reported in the few series published of malignant lymphomas as soft tissue tumors. Remarkable were relatively good prognosis with \"highly malignant\" morphology and preference for involvement of soft tissue even after dissemination. Future studies are requested to shed light on possible specific cellular findings as to phenotype and genotype in malignant lymphoma presenting as soft tissue tumors, as already had been done with subcutaneous T-cell lymphoma and primary lymphoma of the bone."} {"id": "PMID:1283247", "title": "[Non-Hodgkin's lymphoma with primary osseous manifestation, from the files of the Bone Tumor Registry of Westphalia].", "content": "30 cases of non-Hodgkin-lymphoma with primary bone manifestation were selected from the files of the Bone Tumor Registry of Westfalia from 1975 until 1992. Clinical data and radiologic aspects were evaluated. 60% of the lesions were localized within the long bones (femur 10, humerus 6, tibia 2). The lymphomas were classified based on paraffin-embedded material in combination with immunohistochemical findings according to the updated Kiel-classification. 29 B-cell lymphomas and one T-cell lymphoma of medium-sized pleomorphic type were found. 5 B-cell lymphomas were of low and 23 of high malignancy. Almost 50% of the tumors were of centroblastic type. The Kiel-classification was not applicable for one lymphoma, 3 others could not be subclassified because of shrinking artefacts. Prognosis in patients with localized disease (9 cases) was favorable, whereas only 25% of patients with generalized disease (12/cases) survived for 3 years or longer.", "contents": "[Non-Hodgkin's lymphoma with primary osseous manifestation, from the files of the Bone Tumor Registry of Westphalia]. 30 cases of non-Hodgkin-lymphoma with primary bone manifestation were selected from the files of the Bone Tumor Registry of Westfalia from 1975 until 1992. Clinical data and radiologic aspects were evaluated. 60% of the lesions were localized within the long bones (femur 10, humerus 6, tibia 2). The lymphomas were classified based on paraffin-embedded material in combination with immunohistochemical findings according to the updated Kiel-classification. 29 B-cell lymphomas and one T-cell lymphoma of medium-sized pleomorphic type were found. 5 B-cell lymphomas were of low and 23 of high malignancy. Almost 50% of the tumors were of centroblastic type. The Kiel-classification was not applicable for one lymphoma, 3 others could not be subclassified because of shrinking artefacts. Prognosis in patients with localized disease (9 cases) was favorable, whereas only 25% of patients with generalized disease (12/cases) survived for 3 years or longer."} {"id": "PMID:1283248", "title": "[Proliferating cells in Hodgkin's disease].", "content": "We have studied the proliferation fraction of Hodgkin- and Reed-Sternberg (HRS) cells and L&H cells in paraffin sections of 15 cases of classical Hodgkin's disease (HD) (12 nodular sclerosis [NS], 3 mixed cellularity [MC]) and 8 cases of nodular lymphocyte predominant Hodgkin's disease (NLPHD) using an antibody to proliferating cell nuclear antigen (PCNA). By double staining with anti-PCNA and antibodies to B- and T-cells we also determined the growth fraction and immunophenotype of the background lymphocytes in each case. In classical HD 45.3% of HRS cells, and in NLPHD 76.9% of L&H cells were in cycle. In both classical HD and NLPHD the majority of proliferating cells in the background were T-cells with 57.8% respectively 68.5%, whereas only a few B-cells were proliferating in each type of HD.", "contents": "[Proliferating cells in Hodgkin's disease]. We have studied the proliferation fraction of Hodgkin- and Reed-Sternberg (HRS) cells and L&H cells in paraffin sections of 15 cases of classical Hodgkin's disease (HD) (12 nodular sclerosis [NS], 3 mixed cellularity [MC]) and 8 cases of nodular lymphocyte predominant Hodgkin's disease (NLPHD) using an antibody to proliferating cell nuclear antigen (PCNA). By double staining with anti-PCNA and antibodies to B- and T-cells we also determined the growth fraction and immunophenotype of the background lymphocytes in each case. In classical HD 45.3% of HRS cells, and in NLPHD 76.9% of L&H cells were in cycle. In both classical HD and NLPHD the majority of proliferating cells in the background were T-cells with 57.8% respectively 68.5%, whereas only a few B-cells were proliferating in each type of HD."} {"id": "PMID:1283249", "title": "[Which are the proliferating cells in Hodgkin's disease?].", "content": "This investigation characterizes the proliferating cells in Hodgkin's disease. We used the antibody PC 10 which reacts with the proliferating cell nuclear antigen (PCNA) and works on paraffin sections in combination with B- and T-cell markers in a double-staining technique. In all 38 cases of Hodgkin's disease (lymphocyte predominant type n = 10, nodular sclerosis type n = 10, mixed cellularity type n = 10, lymphocyte depletion type n = 8) a high percentage of the Hodgkin and Sternberg-Reed cells (95%-97%) expressed PCNA. There was no statistical significance between the different types. In contrast, only a small amount of the reactive lymphocytes (2.8%-3.4%) demonstrated positivity for PCNA in the four types of Hodgkin's disease. Nearly all of these lymphocytes were T-lymphocytes.", "contents": "[Which are the proliferating cells in Hodgkin's disease?]. This investigation characterizes the proliferating cells in Hodgkin's disease. We used the antibody PC 10 which reacts with the proliferating cell nuclear antigen (PCNA) and works on paraffin sections in combination with B- and T-cell markers in a double-staining technique. In all 38 cases of Hodgkin's disease (lymphocyte predominant type n = 10, nodular sclerosis type n = 10, mixed cellularity type n = 10, lymphocyte depletion type n = 8) a high percentage of the Hodgkin and Sternberg-Reed cells (95%-97%) expressed PCNA. There was no statistical significance between the different types. In contrast, only a small amount of the reactive lymphocytes (2.8%-3.4%) demonstrated positivity for PCNA in the four types of Hodgkin's disease. Nearly all of these lymphocytes were T-lymphocytes."} {"id": "PMID:1283250", "title": "[Borderline between Hodgkin and non-Hodgkin lymphomas with unfavorable clinical course: a clinical, histological and immunohistochemical analysis of 33 cases within the German Hodgkin Lymphoma Study].", "content": "Reevaluation of diagnostic biopsies from 502 patients who entered the German Hodgkin Therapy trial was performed by a panel of four pathologists. Classification revealed 90% of unambiguous Hodgkin-lymphomas (HL), 1.6% of Non-Hodgkin-lymphomas (NHL) and 8.4% of cases difficult to evaluate, reflecting to the well-known problem of the border between these 2 groups of lymphoma. As these cases had the worst prognosis, a second attempt of reclassification, including immunohistochemical studies, was made, resulting in final classifying of 25% of these cases as NHL, 50% as HL, and 25% as further unclassifiable. The most common differential diagnostic problem was separating pleomorphic nodular sclerosing HL from large cell NHL's and HL with rather few Hodgkin- or Reed-Sternberg-cells from Lennerts lymphoma or angioimmunoblastic lymphadenopathy. Immunohistochemistry was helpful for the differential diagnostic decisions in these individual cases. A very high percentage of these problem cases had initially entered the trial as lymphocyte depleted HL, and the large majority of deaths came from the large cell NHL group.", "contents": "[Borderline between Hodgkin and non-Hodgkin lymphomas with unfavorable clinical course: a clinical, histological and immunohistochemical analysis of 33 cases within the German Hodgkin Lymphoma Study]. Reevaluation of diagnostic biopsies from 502 patients who entered the German Hodgkin Therapy trial was performed by a panel of four pathologists. Classification revealed 90% of unambiguous Hodgkin-lymphomas (HL), 1.6% of Non-Hodgkin-lymphomas (NHL) and 8.4% of cases difficult to evaluate, reflecting to the well-known problem of the border between these 2 groups of lymphoma. As these cases had the worst prognosis, a second attempt of reclassification, including immunohistochemical studies, was made, resulting in final classifying of 25% of these cases as NHL, 50% as HL, and 25% as further unclassifiable. The most common differential diagnostic problem was separating pleomorphic nodular sclerosing HL from large cell NHL's and HL with rather few Hodgkin- or Reed-Sternberg-cells from Lennerts lymphoma or angioimmunoblastic lymphadenopathy. Immunohistochemistry was helpful for the differential diagnostic decisions in these individual cases. A very high percentage of these problem cases had initially entered the trial as lymphocyte depleted HL, and the large majority of deaths came from the large cell NHL group."} {"id": "PMID:1283251", "title": "[Immunohistochemical in situ demonstration of cytokines in Hodgkin and non-Hodgkin lymphoma].", "content": "Primary biopsies from 149 patients with malignant lymphomas were examined by histological and immunohistochemical techniques. Twenty eight cases were classified as Hodgkin's disease and 121 as non-Hodgkin's lymphomas. The immunohistochemical distribution of cytokine expression (Il-1 alpha, Il-1 beta, Il-6 and TNF-alpha) was demonstrated in neoplastic cells and in tumor-associated macrophages (TAM). Neoplastic cells showed mostly weak positivity for TNF-alpha in 40% of Hodgkin's disease and in 20% of T cell lymphoma cases. Two groups of malignant lymphomas were established which differed in the numbers of cytokine expressing TAM. The first group consisted of malignant lymphomas which contained large quantities of cytokine-possessing TAM. In the second group significantly lower frequencies of cytokine expressing TAM were found. In both groups high and low grade malignant lymphomas were encountered. There was a significantly positive correlation between the number of Il-6 possessing TAM and the proliferation of lymphoma cells in only the non-Hodgkin's lymphomas. Our results suggest a paracrine tumor growth stimulating mechanism which is created by a self perpetuating cytokine production loop. A supposed cytokine produced by neoplastic cells dependent from their proliferative activity may induce Il-6 secretion by TAM. Il-6 in turn may stimulate the proliferation of the lymphoma cells without maturation thus leading to a self-sustaining growth.", "contents": "[Immunohistochemical in situ demonstration of cytokines in Hodgkin and non-Hodgkin lymphoma]. Primary biopsies from 149 patients with malignant lymphomas were examined by histological and immunohistochemical techniques. Twenty eight cases were classified as Hodgkin's disease and 121 as non-Hodgkin's lymphomas. The immunohistochemical distribution of cytokine expression (Il-1 alpha, Il-1 beta, Il-6 and TNF-alpha) was demonstrated in neoplastic cells and in tumor-associated macrophages (TAM). Neoplastic cells showed mostly weak positivity for TNF-alpha in 40% of Hodgkin's disease and in 20% of T cell lymphoma cases. Two groups of malignant lymphomas were established which differed in the numbers of cytokine expressing TAM. The first group consisted of malignant lymphomas which contained large quantities of cytokine-possessing TAM. In the second group significantly lower frequencies of cytokine expressing TAM were found. In both groups high and low grade malignant lymphomas were encountered. There was a significantly positive correlation between the number of Il-6 possessing TAM and the proliferation of lymphoma cells in only the non-Hodgkin's lymphomas. Our results suggest a paracrine tumor growth stimulating mechanism which is created by a self perpetuating cytokine production loop. A supposed cytokine produced by neoplastic cells dependent from their proliferative activity may induce Il-6 secretion by TAM. Il-6 in turn may stimulate the proliferation of the lymphoma cells without maturation thus leading to a self-sustaining growth."} {"id": "PMID:1283252", "title": "[Bcl-2 in potentials precursors of nodular paragranuloma and its dedifferentiated variant (large cell B-lymphoma)].", "content": "We have investigated seven cases of large cell lymphomas (LCL) developing simultaneously or metachronously to nodular lymphocyte-predominant Hodgkin's disease (nodular paragranuloma, NP) for the presence of EBV and the chromosomal translocation t(14;18) by use of the polymerase chain reaction (PCR). The expression of the bcl-2 oncogene product in these cases and in five cases of progressive transformation of germinal centres as a potential precursor of NP was detected immunohistochemically with the monoclonal antibodies bcl-2-100 and bcl-2-124. All cases investigated were negative for EBV genomic material. The chromosomal translocation t(14;18) was also absent. Expression of the bcl-2 oncogene could be detected only in one case of nodular paragranuloma and in an unrelated case of LCL. Hence, LCL developing out of NP differ from other germinal center derived high-grade lymphomas.", "contents": "[Bcl-2 in potentials precursors of nodular paragranuloma and its dedifferentiated variant (large cell B-lymphoma)]. We have investigated seven cases of large cell lymphomas (LCL) developing simultaneously or metachronously to nodular lymphocyte-predominant Hodgkin's disease (nodular paragranuloma, NP) for the presence of EBV and the chromosomal translocation t(14;18) by use of the polymerase chain reaction (PCR). The expression of the bcl-2 oncogene product in these cases and in five cases of progressive transformation of germinal centres as a potential precursor of NP was detected immunohistochemically with the monoclonal antibodies bcl-2-100 and bcl-2-124. All cases investigated were negative for EBV genomic material. The chromosomal translocation t(14;18) was also absent. Expression of the bcl-2 oncogene could be detected only in one case of nodular paragranuloma and in an unrelated case of LCL. Hence, LCL developing out of NP differ from other germinal center derived high-grade lymphomas."} {"id": "PMID:1283253", "title": "[Influence of Epstein-Barr virus genome on patient survival in Hodgkin's disease].", "content": "In the literature EBV is considered a possible etiologic factor for Hodgkin's disease (HD). We investigated 187 cases of HD for the presence of Epstein Barr virus using the polymerase chain reaction (PCR) technique on formalin fixed, paraffin embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. The 187 cases included all subtypes. 66 cases (35.2%) were positive for EBV DNA. The statistical analysis of follow-up data from 130 patients revealed no influence of EBV DNA on survival time. In our investigation detection of EBV DNA by PCR showed no prognostic relevance for patients with HD.", "contents": "[Influence of Epstein-Barr virus genome on patient survival in Hodgkin's disease]. In the literature EBV is considered a possible etiologic factor for Hodgkin's disease (HD). We investigated 187 cases of HD for the presence of Epstein Barr virus using the polymerase chain reaction (PCR) technique on formalin fixed, paraffin embedded lymph node tissue to clarify the clinical importance of the incidence of this genome. The 187 cases included all subtypes. 66 cases (35.2%) were positive for EBV DNA. The statistical analysis of follow-up data from 130 patients revealed no influence of EBV DNA on survival time. In our investigation detection of EBV DNA by PCR showed no prognostic relevance for patients with HD."} {"id": "PMID:1283254", "title": "[Nodular paragranuloma and Epstein-Barr virus: frequency of EBV DNA and clinical relevance].", "content": "Studies demonstrating Epstein-Barr virus (EBV) DNA in Hodgkin's disease (HD) provide little information about the EBV-status in the lymphocyte predominant subtype (nodular paragranuloma) which is due to the small number of cases investigated. Therefore we studied 99 typical cases of nodular paragranuloma for the presence of EBV-DNA using the polymerase chain reaction (PCR) technique. Genomic DNA was amplifiable in 71 cases; 29 cases (= 40%) were positive for EBV-DNA (EBNA-1). In situ hybridization revealed EBV-RNA (EBER-1) in L&H cells and in a few lymphocytes. PCR results were correlated to clinical follow-up data and did not show any statistically significant relationship between EBV positivity and survival of the patients.", "contents": "[Nodular paragranuloma and Epstein-Barr virus: frequency of EBV DNA and clinical relevance]. Studies demonstrating Epstein-Barr virus (EBV) DNA in Hodgkin's disease (HD) provide little information about the EBV-status in the lymphocyte predominant subtype (nodular paragranuloma) which is due to the small number of cases investigated. Therefore we studied 99 typical cases of nodular paragranuloma for the presence of EBV-DNA using the polymerase chain reaction (PCR) technique. Genomic DNA was amplifiable in 71 cases; 29 cases (= 40%) were positive for EBV-DNA (EBNA-1). In situ hybridization revealed EBV-RNA (EBER-1) in L&H cells and in a few lymphocytes. PCR results were correlated to clinical follow-up data and did not show any statistically significant relationship between EBV positivity and survival of the patients."} {"id": "PMID:1283255", "title": "[Demonstration of Epstein-Barr virus DNA and determination of immunoglobulin and T-cell receptor gene rearrangerments in diagnostic lymph node biopsies from patients with Hodgkin's disease].", "content": "Lymph node biopsies of 52 patients with Hodgkin's disease were analyzed by Southern blot hybridization for the presence of monoclonal rearrangements of immunoglobulin and T cell receptor genes. The same tissues were tested for Epstein-Barr virus DNA by the polymerase chain reaction using four different sets of primers. Monoclonal rearrangements were identified in only four tumors, whereas Epstein-Barr virus was present in 79% of biopsies. A correlation between the degree of infiltration by Reed-Sterberg cells, clonality and the presence of Epstein-Barr virus could not be found. These results are in agreement with similar studies reported in the literature. The nature of the malignant cell in Hodgkin's disease and the role of Epstein-Barr virus in the etiology of this tumor remains to be established.", "contents": "[Demonstration of Epstein-Barr virus DNA and determination of immunoglobulin and T-cell receptor gene rearrangerments in diagnostic lymph node biopsies from patients with Hodgkin's disease]. Lymph node biopsies of 52 patients with Hodgkin's disease were analyzed by Southern blot hybridization for the presence of monoclonal rearrangements of immunoglobulin and T cell receptor genes. The same tissues were tested for Epstein-Barr virus DNA by the polymerase chain reaction using four different sets of primers. Monoclonal rearrangements were identified in only four tumors, whereas Epstein-Barr virus was present in 79% of biopsies. A correlation between the degree of infiltration by Reed-Sterberg cells, clonality and the presence of Epstein-Barr virus could not be found. These results are in agreement with similar studies reported in the literature. The nature of the malignant cell in Hodgkin's disease and the role of Epstein-Barr virus in the etiology of this tumor remains to be established."} {"id": "PMID:1283256", "title": "[Opportunistic malignant lymphomas in SIV infected primates--a model for Epstein-Barr virus associated lymphomas in AIDS].", "content": "In a series of 33 cynomolgus monkeys (Macaca fascicularis) experimentally infected with Simian Immunodeficiency virus (SIV), strain smm3, 13 animals developed malignant Non-Hodgkin lymphomas. These lymphomas presented with unusual primary manifestations like in the orbita, testes, and brain. The morphological features and immunophenotyping identified the tumors as high malignant B-cell lymphomas. In all tumors as well as in tumor-derived cell lines a cynomolgus B-lymphotropic herpes virus (CBLV) with structural homogeneity to the Epstein-Barr virus (EBV) could be demonstrated by Southern blotting with EBV-specific probes. The lymphoma cells also expressed CBLV-associated nuclear antigens involved in B-cell transformation crossreacting with EBNA-specific human sera and monoclonal antibodies. Ig-gene rearrangement studies revealed clonal populations, however, no translocations of the c-myc oncogene could be detected. The lymphomas developing with high frequency in SIV-induced immunodeficiency resemble a major subtype of human EBV-associated AIDS lymphomas. This animal model can therefore be used to further elucidate interactions of HIV and EBV in AIDS-related lymphomagenesis.", "contents": "[Opportunistic malignant lymphomas in SIV infected primates--a model for Epstein-Barr virus associated lymphomas in AIDS]. In a series of 33 cynomolgus monkeys (Macaca fascicularis) experimentally infected with Simian Immunodeficiency virus (SIV), strain smm3, 13 animals developed malignant Non-Hodgkin lymphomas. These lymphomas presented with unusual primary manifestations like in the orbita, testes, and brain. The morphological features and immunophenotyping identified the tumors as high malignant B-cell lymphomas. In all tumors as well as in tumor-derived cell lines a cynomolgus B-lymphotropic herpes virus (CBLV) with structural homogeneity to the Epstein-Barr virus (EBV) could be demonstrated by Southern blotting with EBV-specific probes. The lymphoma cells also expressed CBLV-associated nuclear antigens involved in B-cell transformation crossreacting with EBNA-specific human sera and monoclonal antibodies. Ig-gene rearrangement studies revealed clonal populations, however, no translocations of the c-myc oncogene could be detected. The lymphomas developing with high frequency in SIV-induced immunodeficiency resemble a major subtype of human EBV-associated AIDS lymphomas. This animal model can therefore be used to further elucidate interactions of HIV and EBV in AIDS-related lymphomagenesis."} {"id": "PMID:1283257", "title": "[EBV in malignant lymphomas].", "content": "PCR and in-situ-Hybridization were used to detect EBV-DNA within Hodgkin- and Non-Hodgkin-Lymphomas. By the use of primers for the Bam H1 W fragment we could show EBV-DNA to be associated with 45% Hodgkin- and 25% T-Lymphomas, whereas we could not find EBV-DNA within B-Lymphomas. In about one third of the PCR-positive cases we could localize EBV-DNA mostly in the tumor cell nuclei by in-situ-hybridization.", "contents": "[EBV in malignant lymphomas]. PCR and in-situ-Hybridization were used to detect EBV-DNA within Hodgkin- and Non-Hodgkin-Lymphomas. By the use of primers for the Bam H1 W fragment we could show EBV-DNA to be associated with 45% Hodgkin- and 25% T-Lymphomas, whereas we could not find EBV-DNA within B-Lymphomas. In about one third of the PCR-positive cases we could localize EBV-DNA mostly in the tumor cell nuclei by in-situ-hybridization."} {"id": "PMID:1283258", "title": "[Detection of Epstein-Barr virus genomes in various entities of low and high grade T-cell lymphomas].", "content": "72 T-cell lymphomas were analyzed for the presence of Epstein-Barr virus DNA using Southern or dot blot hybridization. EBV DNA was found in 25 peripheral T-cell lymphomas and in none of 6 T-lymphoblastic tumors. A high prevalence of EBV was detected in AILD type, Lennert's, pleomorphic medium and large cell nodal lymphomas and in upper aerodigestive tract lymphoma biopsies. Clonotypic analysis revealed monoclonal as well as oligoclonal viral populations. The possible influence of EBV in lymphomagenesis, the impact of virus-mediated interactions in the B- and T-cell system and factors involving site of tumor development are discussed.", "contents": "[Detection of Epstein-Barr virus genomes in various entities of low and high grade T-cell lymphomas]. 72 T-cell lymphomas were analyzed for the presence of Epstein-Barr virus DNA using Southern or dot blot hybridization. EBV DNA was found in 25 peripheral T-cell lymphomas and in none of 6 T-lymphoblastic tumors. A high prevalence of EBV was detected in AILD type, Lennert's, pleomorphic medium and large cell nodal lymphomas and in upper aerodigestive tract lymphoma biopsies. Clonotypic analysis revealed monoclonal as well as oligoclonal viral populations. The possible influence of EBV in lymphomagenesis, the impact of virus-mediated interactions in the B- and T-cell system and factors involving site of tumor development are discussed."} {"id": "PMID:1283259", "title": "[Heterogeneous Epstein-Barr virus infection patterns in peripheral T cell lymphoma of the angioimmunoblastic lymphadenopathy type].", "content": "32 cases of T cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for their association with Epstein-Barr virus (EBV). Polymerase chain reaction (PCR) for detection of EBV-DNA and in situ hybridization for EBV-encoded small nuclear RNAs (EBER) produced almost identical results, showing that all but one of AILD-TCL cases contained EBV genomes. Three distinctive patterns of EBV infection were observed after immunophenotypical characterization of EBER positive cells: 1. predominant infection of B-immunoblasts (26% of the cases), 2. predominant infection of neoplastic T cells (42% of the cases) and 3. infection of few small lymphocytes (32% of the cases). EBV-encoded latent membrane protein was frequently detectable in cases exhibiting patterns 1 and 2. These findings suggest that, in AILD-TCL patients B cells and especially T cells are highly susceptible to a persistent EBV infection which may lead to a growth advantage of infected cells.", "contents": "[Heterogeneous Epstein-Barr virus infection patterns in peripheral T cell lymphoma of the angioimmunoblastic lymphadenopathy type]. 32 cases of T cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for their association with Epstein-Barr virus (EBV). Polymerase chain reaction (PCR) for detection of EBV-DNA and in situ hybridization for EBV-encoded small nuclear RNAs (EBER) produced almost identical results, showing that all but one of AILD-TCL cases contained EBV genomes. Three distinctive patterns of EBV infection were observed after immunophenotypical characterization of EBER positive cells: 1. predominant infection of B-immunoblasts (26% of the cases), 2. predominant infection of neoplastic T cells (42% of the cases) and 3. infection of few small lymphocytes (32% of the cases). EBV-encoded latent membrane protein was frequently detectable in cases exhibiting patterns 1 and 2. These findings suggest that, in AILD-TCL patients B cells and especially T cells are highly susceptible to a persistent EBV infection which may lead to a growth advantage of infected cells."} {"id": "PMID:1283260", "title": "[Classification and virus expression of primary cerebral lymphomas].", "content": "Fourty-three primary cerebral lymphomas (PCL) were histologically classified and examined for genome expression of Epstein Barr Virus (EBV) and human herpes virus 6 (HHV6) using dot blotting, polymerase chain reaction, and Southern blotting. Only 20 tumors (16 high grade and 4 low grade lymphomas) could be suitably placed into a category of the Updated Kiel Classification, whereas the non-classified 23 tumors were highly malignant B-lymphomas and referred to as small-cell (SC) or large-cell (LC) blastic PCL. Most of the LC PCL showed a tumor-like infiltration pattern with high cellular density and little remaining parenchyma, whereas the SC PCL more often showed an inflammation-like pattern characterized by loose arrangement of tumor cells and marked astrocytic, microglial and T-lymphocytic reaction. EBV genome was found in 3/3 AIDS cases, but in none of 40 immunocompetent cases, while HHV6 was detected in 2 tumors of immunocompetent patients. We conclude that (1) the Updated Kiel Classification is not applicable to a majority of PCL, and (2) EBV and HHV6 do not appear to play a major role in the pathogenesis of PCL in immunocompetent subjects.", "contents": "[Classification and virus expression of primary cerebral lymphomas]. Fourty-three primary cerebral lymphomas (PCL) were histologically classified and examined for genome expression of Epstein Barr Virus (EBV) and human herpes virus 6 (HHV6) using dot blotting, polymerase chain reaction, and Southern blotting. Only 20 tumors (16 high grade and 4 low grade lymphomas) could be suitably placed into a category of the Updated Kiel Classification, whereas the non-classified 23 tumors were highly malignant B-lymphomas and referred to as small-cell (SC) or large-cell (LC) blastic PCL. Most of the LC PCL showed a tumor-like infiltration pattern with high cellular density and little remaining parenchyma, whereas the SC PCL more often showed an inflammation-like pattern characterized by loose arrangement of tumor cells and marked astrocytic, microglial and T-lymphocytic reaction. EBV genome was found in 3/3 AIDS cases, but in none of 40 immunocompetent cases, while HHV6 was detected in 2 tumors of immunocompetent patients. We conclude that (1) the Updated Kiel Classification is not applicable to a majority of PCL, and (2) EBV and HHV6 do not appear to play a major role in the pathogenesis of PCL in immunocompetent subjects."} {"id": "PMID:1283261", "title": "[EBV-lymphadenitis: diagnostic possibilities using immunohistochemistry and in situ hybridization].", "content": "EBV infections were studied in paraffin embedded lymph node specimens (n = 20) on DNA, protein, and histological level. The lymph nodes were obtained from 20 patients all testing positive for EBV serologically. The EBV DNA was detected by non radioactive in-situ-hybridisation using the BamHI W fragment of the virus. The EBV latent membrane protein was detected immunohistochemically using the LMP antibody (DAKO). Infected cells were characterized by monoclonal B cell antibodies. By in-situ-hybridization we found positive signals for EBV in all specimens. In contrast, no LMP was detectable immunohistochemically in 2/20 lymph nodes.", "contents": "[EBV-lymphadenitis: diagnostic possibilities using immunohistochemistry and in situ hybridization]. EBV infections were studied in paraffin embedded lymph node specimens (n = 20) on DNA, protein, and histological level. The lymph nodes were obtained from 20 patients all testing positive for EBV serologically. The EBV DNA was detected by non radioactive in-situ-hybridisation using the BamHI W fragment of the virus. The EBV latent membrane protein was detected immunohistochemically using the LMP antibody (DAKO). Infected cells were characterized by monoclonal B cell antibodies. By in-situ-hybridization we found positive signals for EBV in all specimens. In contrast, no LMP was detectable immunohistochemically in 2/20 lymph nodes."} {"id": "PMID:1283262", "title": "[Follicular dendritic cells in extranodal non-Hodgkin's lymphomas].", "content": "Extranodal lymphomas of the thyroid (n = 19), kidney (n = 15) and testis (n = 30) were investigated histologically and immunohistochemically using the monoclonal antibody Ki-FDC1P, which recognizes follicular dendritic cells on paraffin sections. Only lymphomas of the thyroid were of MALT-lymphoma type and contained tumor associated abortive follicles of follicular dendritic cells. In kidney and testis, no MALT-Lymphomas were found. Lymphoepithelial lesions, a hallmark of MALT-Lymphomas, occurred not only in thyroid MALT-lymphomas, but also in testicular centroblastic lymphomas (lacking other features of MALT-lymphomas). Therefore, lymphoepithelial lesions are not specific for MALT-lymphomas.", "contents": "[Follicular dendritic cells in extranodal non-Hodgkin's lymphomas]. Extranodal lymphomas of the thyroid (n = 19), kidney (n = 15) and testis (n = 30) were investigated histologically and immunohistochemically using the monoclonal antibody Ki-FDC1P, which recognizes follicular dendritic cells on paraffin sections. Only lymphomas of the thyroid were of MALT-lymphoma type and contained tumor associated abortive follicles of follicular dendritic cells. In kidney and testis, no MALT-Lymphomas were found. Lymphoepithelial lesions, a hallmark of MALT-Lymphomas, occurred not only in thyroid MALT-lymphomas, but also in testicular centroblastic lymphomas (lacking other features of MALT-lymphomas). Therefore, lymphoepithelial lesions are not specific for MALT-lymphomas."} {"id": "PMID:1283263", "title": "[Sinus lining cells:morphology, function and neoplasia].", "content": "Lymph node sinuses consist mainly of sinus lining cells with clear dendritic morphology. Enzyme cytochemical and immune phenotypical analysis classify sinus lining cells as an intermediate cell type linking monocyte/macrophage to follicular dendritic cells, which are accepted immune accessory cells to humoral immune response. Labeling studies indicate sinus lining cells to hematogenous and possible monocytogenous in origin. In functional term sinus lining cells bind and present soluble antigen as the first cell type following antigen pulse. In addition sinus lining cells bind carcinoma cells and may play a role in metastasis. Sinus lining cells give rise to a well defined entity of neoplasia which is proposed to be termed sinus lining cell reticulosarcoma. In this presentation a case report exemplifies such a new entity.", "contents": "[Sinus lining cells:morphology, function and neoplasia]. Lymph node sinuses consist mainly of sinus lining cells with clear dendritic morphology. Enzyme cytochemical and immune phenotypical analysis classify sinus lining cells as an intermediate cell type linking monocyte/macrophage to follicular dendritic cells, which are accepted immune accessory cells to humoral immune response. Labeling studies indicate sinus lining cells to hematogenous and possible monocytogenous in origin. In functional term sinus lining cells bind and present soluble antigen as the first cell type following antigen pulse. In addition sinus lining cells bind carcinoma cells and may play a role in metastasis. Sinus lining cells give rise to a well defined entity of neoplasia which is proposed to be termed sinus lining cell reticulosarcoma. In this presentation a case report exemplifies such a new entity."} {"id": "PMID:1283264", "title": "[Morphological and immunohistochemical findings on the frequency of intranuclear immunoglobulin inclusions (Dutcher bodies) in malignant B-cell lymphomas].", "content": "318 cases of 682 malignant B-cell lymphomas reacted positive for cIg. 66 of them showed Dutcher bodies (DB). DB were found in about 22% of plasmacytomas, 17% of immunocytomas, and in 7.5% of follicular lymphomas and polymorphic centroblastomas, respectively. Regarding only the cIg-positive cases, DB occurred in about 27% of immunocytomas, 20% of follicular lymphomas and 18% of polymorphic centroblastomas. A single case of prolymphocytic leukaemia, centrocytoma, monomorphic centroblastoma, and immunoblastoma each showed also DB. Usually, DB-positive plasmacytomas showed kappa, alpha, and J-chains. The remaining lymphomas mostly expressed kappa, my, and J-chains. In conclusion Dutcher bodies can occur with any cIg-producing B-cell lymphoma. They are not limited to immunocytomas.", "contents": "[Morphological and immunohistochemical findings on the frequency of intranuclear immunoglobulin inclusions (Dutcher bodies) in malignant B-cell lymphomas]. 318 cases of 682 malignant B-cell lymphomas reacted positive for cIg. 66 of them showed Dutcher bodies (DB). DB were found in about 22% of plasmacytomas, 17% of immunocytomas, and in 7.5% of follicular lymphomas and polymorphic centroblastomas, respectively. Regarding only the cIg-positive cases, DB occurred in about 27% of immunocytomas, 20% of follicular lymphomas and 18% of polymorphic centroblastomas. A single case of prolymphocytic leukaemia, centrocytoma, monomorphic centroblastoma, and immunoblastoma each showed also DB. Usually, DB-positive plasmacytomas showed kappa, alpha, and J-chains. The remaining lymphomas mostly expressed kappa, my, and J-chains. In conclusion Dutcher bodies can occur with any cIg-producing B-cell lymphoma. They are not limited to immunocytomas."} {"id": "PMID:1283265", "title": "[Expression of beta 1 integrins in normal B lymphocytes at different stages of development and in B cell neoplasias].", "content": "VLA-1 to -6 are cell surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. In addition, VLA-4 binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion prerogative for lymphocyte extravasation or \"homing\". Using frozen tissue of normal lymphoid organs and of 100 morphologically and immunologically typed B cell neoplasias, monoclonal antibodies to all six VLA-alpha subunits and to the common beta 1-chain were applied to serial sections. VLAs were found differentially expressed in cytologically and microtopographically defined B cell subsets [follicular mantle zone cells (MZ), follicular center cells (FC), extrafollicular cells (EF), and plasma cells (PC)] of normal spleen, lymph node, and thymic medulla (which contains an EF compartment). Thus, these cell types, which correspond to discrete stages of B cell development, can also be defined by their VLA status. Acute B lymphoblastic leukemia (ALL) was VLA-1-, 2-, 3 +/-, 4 +/-, 5 +/-, 6-. The VLA-1-, -2 +/-, -3+, -4+, -5+, -6- phenotype of chronic B lymphocytic leukemia (CLL) resembled that of MZ. Hairy cell leukemia (HCL) differed from CLL in its tendency to lack VLA-2, in its consistent lack of VLA-3, and altogether resembled splenic EF in its VLA profile. Mantle zone lymphoma (MZL) consistently expressed VLA-3 and -4 and frequently VLA-5. Nodal follicular center cell lymphomas (FCCL) were VLA-1- and -2- and very rarely expressed VLA-5 and -6. Thus, FCCL although roughly corresponding to FC, tended to aberrantly express VLA-3 and/or VLA-4. Burkitt's lymphoma resembled FCCL but expressed VLA-4 more frequently and at higher levels.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "[Expression of beta 1 integrins in normal B lymphocytes at different stages of development and in B cell neoplasias]. VLA-1 to -6 are cell surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. In addition, VLA-4 binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion prerogative for lymphocyte extravasation or \"homing\". Using frozen tissue of normal lymphoid organs and of 100 morphologically and immunologically typed B cell neoplasias, monoclonal antibodies to all six VLA-alpha subunits and to the common beta 1-chain were applied to serial sections. VLAs were found differentially expressed in cytologically and microtopographically defined B cell subsets [follicular mantle zone cells (MZ), follicular center cells (FC), extrafollicular cells (EF), and plasma cells (PC)] of normal spleen, lymph node, and thymic medulla (which contains an EF compartment). Thus, these cell types, which correspond to discrete stages of B cell development, can also be defined by their VLA status. Acute B lymphoblastic leukemia (ALL) was VLA-1-, 2-, 3 +/-, 4 +/-, 5 +/-, 6-. The VLA-1-, -2 +/-, -3+, -4+, -5+, -6- phenotype of chronic B lymphocytic leukemia (CLL) resembled that of MZ. Hairy cell leukemia (HCL) differed from CLL in its tendency to lack VLA-2, in its consistent lack of VLA-3, and altogether resembled splenic EF in its VLA profile. Mantle zone lymphoma (MZL) consistently expressed VLA-3 and -4 and frequently VLA-5. Nodal follicular center cell lymphomas (FCCL) were VLA-1- and -2- and very rarely expressed VLA-5 and -6. Thus, FCCL although roughly corresponding to FC, tended to aberrantly express VLA-3 and/or VLA-4. Burkitt's lymphoma resembled FCCL but expressed VLA-4 more frequently and at higher levels.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283266", "title": "[Expression of APO-1, a cell surface molecule mediating apoptosis, during normal B cell ontogeny and in B cell tumors. Co-expression and coregulation of APO-1 and ICAM-1 (CD54) in germinal central cells].", "content": "APO-1 is a 48kDa transmembrane glycoprotein and belongs to the NGF/TNF receptor family of surface molecules. Cross-linking of APO-1 induces apoptotic cell death in sensitive cells. Here we show that APO-1 is an activation molecule on B cells. It could be induced/enhanced on dense and buoyant tonsillar B cells, respectively, through surface immunoglobulin cross-linking in combination with interleukin-2 or by interferon-gamma together with tumor necrosis factor-alpha. These conditions also increased the amount of intercellular adhesion molecule-1 (ICAM-1; CD54) on these cells. Epstein-Barr virus transformants of peripheral B cells co-expressed APO-1 and CD54 at very high levels. Immunohistologically, APO-1 was detectable at low levels in a subpopulation of follicular center B blasts and, at higher levels, in sinusoidal B cells. APO-1 was undetectable in follicular mantle B cells and plasma cells. Neoplastic B cell essentially mimicked their reactive counterpart with regard to APO-1 and CD54 expression.", "contents": "[Expression of APO-1, a cell surface molecule mediating apoptosis, during normal B cell ontogeny and in B cell tumors. Co-expression and coregulation of APO-1 and ICAM-1 (CD54) in germinal central cells]. APO-1 is a 48kDa transmembrane glycoprotein and belongs to the NGF/TNF receptor family of surface molecules. Cross-linking of APO-1 induces apoptotic cell death in sensitive cells. Here we show that APO-1 is an activation molecule on B cells. It could be induced/enhanced on dense and buoyant tonsillar B cells, respectively, through surface immunoglobulin cross-linking in combination with interleukin-2 or by interferon-gamma together with tumor necrosis factor-alpha. These conditions also increased the amount of intercellular adhesion molecule-1 (ICAM-1; CD54) on these cells. Epstein-Barr virus transformants of peripheral B cells co-expressed APO-1 and CD54 at very high levels. Immunohistologically, APO-1 was detectable at low levels in a subpopulation of follicular center B blasts and, at higher levels, in sinusoidal B cells. APO-1 was undetectable in follicular mantle B cells and plasma cells. Neoplastic B cell essentially mimicked their reactive counterpart with regard to APO-1 and CD54 expression."} {"id": "PMID:1283267", "title": "[Hodgkin's disease--an entity?].", "content": "Since 26 years Hodgkins disease is classified according to the Rye classification into 4 types. This classification is based on morphology and has turned out to be clinically relevant. However, sometimes the classification on morphological and immunohistochemical ground can be difficult to put a special case in a defined category of the 4 types. In addition, there seems to be no sharp, or well defined borders between Hodgkin's disease and Non-Hodgkin's lymphomas, especially T-cell lymphomas. Immunophenotyping of small lymphocytes and detection of follicular dendritic cells can demonstrate typical patterns in different types of Hodgkin's disease. In all types of Hodgkin's disease there is the same amount of proliferating small T-cells present. Hodgkin cells are lymphoid cells with B- or T-cell markers. Hodgkin cells of nodular para-granuloma (lymphocyte predominant type of Hodgkin's disease) show m-RNA for one light chain in the cytoplasm which can be visualized by in situ-hybridization. A new technique called \"molecular histology\" is applied to Hodgkin's disease. This is a single cell PCR of immunostained cells extracted from tissue sections by a micromanipulator. This technique enables us for the first time to demonstrate light chain and heavy chain gene rearrangements in Hodgkin cells of nodular sclerosis and mixed cellularity type. Hodgkin's disease seems to be no single entity but a heterogenous group of B- and possibly T-cell lymphomas. In the B-cell types Hodgkin cells are probably pre-B and B-cells.", "contents": "[Hodgkin's disease--an entity?]. Since 26 years Hodgkins disease is classified according to the Rye classification into 4 types. This classification is based on morphology and has turned out to be clinically relevant. However, sometimes the classification on morphological and immunohistochemical ground can be difficult to put a special case in a defined category of the 4 types. In addition, there seems to be no sharp, or well defined borders between Hodgkin's disease and Non-Hodgkin's lymphomas, especially T-cell lymphomas. Immunophenotyping of small lymphocytes and detection of follicular dendritic cells can demonstrate typical patterns in different types of Hodgkin's disease. In all types of Hodgkin's disease there is the same amount of proliferating small T-cells present. Hodgkin cells are lymphoid cells with B- or T-cell markers. Hodgkin cells of nodular para-granuloma (lymphocyte predominant type of Hodgkin's disease) show m-RNA for one light chain in the cytoplasm which can be visualized by in situ-hybridization. A new technique called \"molecular histology\" is applied to Hodgkin's disease. This is a single cell PCR of immunostained cells extracted from tissue sections by a micromanipulator. This technique enables us for the first time to demonstrate light chain and heavy chain gene rearrangements in Hodgkin cells of nodular sclerosis and mixed cellularity type. Hodgkin's disease seems to be no single entity but a heterogenous group of B- and possibly T-cell lymphomas. In the B-cell types Hodgkin cells are probably pre-B and B-cells."} {"id": "PMID:1283268", "title": "[Detection of clonal immunoglobulin rearrangements in paraffin embedded tissues by PCR].", "content": "A polymerase chain reaction based method was established using immunoglobulin VH and VK gene rearrangements as markers to detect clonal B cell populations in paraffin embedded sections. Family specific VH and VK primers are used in separate reactions together with the corresponding J primers to amplify rearranged VH and VK genes from genomic DNA. This allows to distinguish clonal from polyclonal B cell populations in most of the cases. The method may be helpful in routine diagnosis of B cell NHL and some morphological and immunohistochemical difficult cases.", "contents": "[Detection of clonal immunoglobulin rearrangements in paraffin embedded tissues by PCR]. A polymerase chain reaction based method was established using immunoglobulin VH and VK gene rearrangements as markers to detect clonal B cell populations in paraffin embedded sections. Family specific VH and VK primers are used in separate reactions together with the corresponding J primers to amplify rearranged VH and VK genes from genomic DNA. This allows to distinguish clonal from polyclonal B cell populations in most of the cases. The method may be helpful in routine diagnosis of B cell NHL and some morphological and immunohistochemical difficult cases."} {"id": "PMID:1283269", "title": "[Tumor proliferation, MDR phenotype and tumor associated t-lymphocytes in non-Hodgkin's lymphomas].", "content": "In this study we examined the P170-expression (mdr-phenotype) in 42 non-Hodgkin's Lymphomas with variant entities immunohistochemically with the mab JSB1. The mdr-phenotype was related to the tumor proliferation as measured by Ki67-expression and AgNOR numbers. Furthermore the mdr-phenotype was related to the tumor associated T-lymphocytes. The mdr-phenotype showed no relation to histological type and the proliferation of the tumor. There was a positive correlation between the mdr-phenotype and CD2-reactive lymphocytes. There was also a significant positive correlation between CD4-reactive lymphocytes and the mean number of AgNOR's. Possibly P170-expression and proliferation of the tumor cells have a lymphotactic effect on T-lymphocytes. The latter could promote tumor progression by means of paracrine mechanisms.", "contents": "[Tumor proliferation, MDR phenotype and tumor associated t-lymphocytes in non-Hodgkin's lymphomas]. In this study we examined the P170-expression (mdr-phenotype) in 42 non-Hodgkin's Lymphomas with variant entities immunohistochemically with the mab JSB1. The mdr-phenotype was related to the tumor proliferation as measured by Ki67-expression and AgNOR numbers. Furthermore the mdr-phenotype was related to the tumor associated T-lymphocytes. The mdr-phenotype showed no relation to histological type and the proliferation of the tumor. There was a positive correlation between the mdr-phenotype and CD2-reactive lymphocytes. There was also a significant positive correlation between CD4-reactive lymphocytes and the mean number of AgNOR's. Possibly P170-expression and proliferation of the tumor cells have a lymphotactic effect on T-lymphocytes. The latter could promote tumor progression by means of paracrine mechanisms."} {"id": "PMID:1283270", "title": "[B-cells in thymic epithelial tumors: phenotype, distribution and relation to the intramedullary B-cell population of the normal thymus].", "content": "Immunohistochemical analysis of 26 thymomas and thymic carcinomas revealed the occurrence of two different intratumoral B-cell populations. High numbers of B-lymphocytes with formation of lymphoid follicles were found in the extra-epithelial perivascular spaces of cortical thymomas and well differentiated thymic carcinomas associated with myasthenia gravis. On the other hand, B-cells within the epithelial meshwork frequently occurred in organoid medullary islands of predominantly cortical and cortical thymomas. In their distribution and phenotype, these cells correspond to the intramedullary B-cell population of the normal thymus, reflecting a specific intratumoral B-cell homing dependent on medullary epithelial differentiation.", "contents": "[B-cells in thymic epithelial tumors: phenotype, distribution and relation to the intramedullary B-cell population of the normal thymus]. Immunohistochemical analysis of 26 thymomas and thymic carcinomas revealed the occurrence of two different intratumoral B-cell populations. High numbers of B-lymphocytes with formation of lymphoid follicles were found in the extra-epithelial perivascular spaces of cortical thymomas and well differentiated thymic carcinomas associated with myasthenia gravis. On the other hand, B-cells within the epithelial meshwork frequently occurred in organoid medullary islands of predominantly cortical and cortical thymomas. In their distribution and phenotype, these cells correspond to the intramedullary B-cell population of the normal thymus, reflecting a specific intratumoral B-cell homing dependent on medullary epithelial differentiation."} {"id": "PMID:1283271", "title": "[Neurofilament expression in thymic epithelial tumors and anti-axonal autoantibodies in myasthenia gravis: a model for autoimmunity by abnormal T cell selection].", "content": "Thymic epithelial tumors from myasthenia gravis (MG) patients and non-neoplastic thymuses were investigated by immunohistochemistry for the expression of neurofilament (NF) epitopes. There was little immunoreactivity confined to the medulla in non-neoplastic thymuses and a faint staining only for a 200 kD NF epitope in medullary and mixed thymomas. In contrast, cortical thymomas and well-differentiated thymic carcinomas expressed epitopes of the 68 kD and 160 kD NF. Demonstrating anti-axonal and anti-NF autoantibodies in thymoma patients we conclude that \"false-positive T cell selection\" is a mechanism of autoimmunity in paraneoplastic MG.", "contents": "[Neurofilament expression in thymic epithelial tumors and anti-axonal autoantibodies in myasthenia gravis: a model for autoimmunity by abnormal T cell selection]. Thymic epithelial tumors from myasthenia gravis (MG) patients and non-neoplastic thymuses were investigated by immunohistochemistry for the expression of neurofilament (NF) epitopes. There was little immunoreactivity confined to the medulla in non-neoplastic thymuses and a faint staining only for a 200 kD NF epitope in medullary and mixed thymomas. In contrast, cortical thymomas and well-differentiated thymic carcinomas expressed epitopes of the 68 kD and 160 kD NF. Demonstrating anti-axonal and anti-NF autoantibodies in thymoma patients we conclude that \"false-positive T cell selection\" is a mechanism of autoimmunity in paraneoplastic MG."} {"id": "PMID:1283272", "title": "[Cysts and tumors of the jaw bone].", "content": "The new entities of cysts and odontogenic tumors of the second edition of WHO \"Histological Typing of Odontogenic Tumors\" (Kramer et al., 1992) are presented. The classification is based on tumor behavior. The benign epithelial odontogenic tumors are classified in relation to tooth development. The malignant odontogenic tumors are subdivided in carcinomas, sarcomas and carcinosarcomas, which are very rare. This international classification has the purpose to make rare cases comparable, so that more detailed knowledge of their characteristics can be achieved. Types of bone tumor that also occur in other parts of the skeleton are not discussed here.", "contents": "[Cysts and tumors of the jaw bone]. The new entities of cysts and odontogenic tumors of the second edition of WHO \"Histological Typing of Odontogenic Tumors\" (Kramer et al., 1992) are presented. The classification is based on tumor behavior. The benign epithelial odontogenic tumors are classified in relation to tooth development. The malignant odontogenic tumors are subdivided in carcinomas, sarcomas and carcinosarcomas, which are very rare. This international classification has the purpose to make rare cases comparable, so that more detailed knowledge of their characteristics can be achieved. Types of bone tumor that also occur in other parts of the skeleton are not discussed here."} {"id": "PMID:1283273", "title": "[Clinical and prognosis relevance of the Kiel classification of non-Hodgkin lymphomas].", "content": "The Kiel classification of non-Hodgkin lymphomas (NHL) identifies distinct entities by morphological and immunological criteria, subdivided into those of low and high grade malignancy and of B- or T-cell subtype. Numerous clinical studies have proven the clinical and prognostic relevance of this classification scheme although the degree of malignancy alone cannot be automatically equated with prognosis. Thus, histological low grade malignancy correlates with favorable response to therapy in all, but with long term survival only in some clearly defined low grade NHL and final cure is achieved in none of them so far. High grade malignancy corresponds to the aggressive spontaneous course of these NHL but is contrasted with the mostly favorable response to therapy and the chance of cure. The immunological T-cell subtype is clearly associated with an inferior prognosis. Additional biological features of NHL, namely chromosomal aberrations and the status of clonality will contribute to a more differentiated view of NHL and will possibly prove to bear prognostic potential.", "contents": "[Clinical and prognosis relevance of the Kiel classification of non-Hodgkin lymphomas]. The Kiel classification of non-Hodgkin lymphomas (NHL) identifies distinct entities by morphological and immunological criteria, subdivided into those of low and high grade malignancy and of B- or T-cell subtype. Numerous clinical studies have proven the clinical and prognostic relevance of this classification scheme although the degree of malignancy alone cannot be automatically equated with prognosis. Thus, histological low grade malignancy correlates with favorable response to therapy in all, but with long term survival only in some clearly defined low grade NHL and final cure is achieved in none of them so far. High grade malignancy corresponds to the aggressive spontaneous course of these NHL but is contrasted with the mostly favorable response to therapy and the chance of cure. The immunological T-cell subtype is clearly associated with an inferior prognosis. Additional biological features of NHL, namely chromosomal aberrations and the status of clonality will contribute to a more differentiated view of NHL and will possibly prove to bear prognostic potential."} {"id": "PMID:1283274", "title": "Homing receptors and lymphocyte migration.", "content": "Lymphocyte migration and recirculation of lymphocytes between the lymphoid organs and other tissues is thought to be essential for effective immunologic surveillance and dissemination of the immune response. In addition, lymphocyte recirculation may also be important in the segregation of lymphocytes with particular functions in the different lymphoid tissues. Furthermore, insight in the molecular basis of these processes may help us to understand lymphoma spreading and metastatic invasion of carcinoma cells.", "contents": "Homing receptors and lymphocyte migration. Lymphocyte migration and recirculation of lymphocytes between the lymphoid organs and other tissues is thought to be essential for effective immunologic surveillance and dissemination of the immune response. In addition, lymphocyte recirculation may also be important in the segregation of lymphocytes with particular functions in the different lymphoid tissues. Furthermore, insight in the molecular basis of these processes may help us to understand lymphoma spreading and metastatic invasion of carcinoma cells."} {"id": "PMID:1283275", "title": "[Malignant lymphomas in spleen--morphology and microenvironment].", "content": "The different entities of malignant lymphomas in the spleen exhibit characteristic stage-dependent infiltration patterns which, in conjunction with cytologic findings, may be employed for diagnostic purposes. These infiltration patterns result from complex interactions between neoplastic and non-neoplastic splenic cell populations which are only incompletely understood. These interactions are governed by intrinsic properties of the involved cell populations, e.g. surface receptors, proliferation activity, cytokine production, immunocompetence etc., as well as by extrinsic factors, e.g. splenic microanatomy and the behavior of splenic immunocompetent and accessory cells which are responsible for the highly organized splenic microenvironments.", "contents": "[Malignant lymphomas in spleen--morphology and microenvironment]. The different entities of malignant lymphomas in the spleen exhibit characteristic stage-dependent infiltration patterns which, in conjunction with cytologic findings, may be employed for diagnostic purposes. These infiltration patterns result from complex interactions between neoplastic and non-neoplastic splenic cell populations which are only incompletely understood. These interactions are governed by intrinsic properties of the involved cell populations, e.g. surface receptors, proliferation activity, cytokine production, immunocompetence etc., as well as by extrinsic factors, e.g. splenic microanatomy and the behavior of splenic immunocompetent and accessory cells which are responsible for the highly organized splenic microenvironments."} {"id": "PMID:1283277", "title": "[Cytogenetics of malignant lymphomas].", "content": "Cytogenetic findings contribute not only to a detailed classification of malignant lymphomas, but also to better prediction of prognosis. Therefore cytogenetic findings gain increasing importance in lymphoma diagnosis. Here, the characteristic chromosome abnormalities t(8;14)(q24;q32), t(2;8)(p12;q24), t(8;22)(q24;q11), t(14;18)(q32;q21), t(11;14)(q13;q32), + 12, + 3 and t(2;5)(p23;q35) and their molecular consequences are described.", "contents": "[Cytogenetics of malignant lymphomas]. Cytogenetic findings contribute not only to a detailed classification of malignant lymphomas, but also to better prediction of prognosis. Therefore cytogenetic findings gain increasing importance in lymphoma diagnosis. Here, the characteristic chromosome abnormalities t(8;14)(q24;q32), t(2;8)(p12;q24), t(8;22)(q24;q11), t(14;18)(q32;q21), t(11;14)(q13;q32), + 12, + 3 and t(2;5)(p23;q35) and their molecular consequences are described."} {"id": "PMID:1283278", "title": "[Molecular genetics of malignant non-Hodgkin's lymphoma].", "content": "Molecular genetical analyses are a valuable adjunct in the diagnosis and biological characterization of malignant lymphomas. They help to define clonality, lymphocyte lineage, and stage of differentiation of the lymphocyte clone. Investigations on the immune receptor gene rearrangement status can now be carried out by the fast and robust polymerase chain reaction (PCR) technique. However, this approach has its drawbacks and cannot completely substitute for Southern Blot experiments. Oncogene rearrangements are used not only to define clonality, but also give an idea about the origin of a lymphocyte clone in malignant lymphoma from a morphologically defined lymph node compartment. One has to be aware of the fact that gene rearrangement studies can only provide reliable results on the basis of a sound morphological evaluation of the lymphoid tumour tissue and that clonality of a lymphoproliferative disease does not necessarily imply a malignant course of disease for the patient.", "contents": "[Molecular genetics of malignant non-Hodgkin's lymphoma]. Molecular genetical analyses are a valuable adjunct in the diagnosis and biological characterization of malignant lymphomas. They help to define clonality, lymphocyte lineage, and stage of differentiation of the lymphocyte clone. Investigations on the immune receptor gene rearrangement status can now be carried out by the fast and robust polymerase chain reaction (PCR) technique. However, this approach has its drawbacks and cannot completely substitute for Southern Blot experiments. Oncogene rearrangements are used not only to define clonality, but also give an idea about the origin of a lymphocyte clone in malignant lymphoma from a morphologically defined lymph node compartment. One has to be aware of the fact that gene rearrangement studies can only provide reliable results on the basis of a sound morphological evaluation of the lymphoid tumour tissue and that clonality of a lymphoproliferative disease does not necessarily imply a malignant course of disease for the patient."} {"id": "PMID:1283279", "title": "[Cytokines and malignant lymphomas].", "content": "Cytokines are potent modulators of the physiological immune response. A number of reactive processes are associated with a deregulation of this cytokine expression. Animal models with transgenic mice or transfection experiments have shown that an autocrine or paracrine pathway might be involved in tumor progression and/or tumorigenesis. The study of cytokine expression in malignant lymphomas showed a heterogeneous expression pattern with a number of cases which quantitatively show indications for a marked deregulation of the cytokine expression. The expression od IL-7 and IL-9 seem to be special features of Hodgkin's disease and large cell anaplastic lymphomas. Transfection experiment with IL-9 into mouse T cells results in an autocrine loop and tumorigenesis of the transfected cells. These tumors share a number of similarities to Hodgkin's disease and large cell anaplastic lymphomas in human.", "contents": "[Cytokines and malignant lymphomas]. Cytokines are potent modulators of the physiological immune response. A number of reactive processes are associated with a deregulation of this cytokine expression. Animal models with transgenic mice or transfection experiments have shown that an autocrine or paracrine pathway might be involved in tumor progression and/or tumorigenesis. The study of cytokine expression in malignant lymphomas showed a heterogeneous expression pattern with a number of cases which quantitatively show indications for a marked deregulation of the cytokine expression. The expression od IL-7 and IL-9 seem to be special features of Hodgkin's disease and large cell anaplastic lymphomas. Transfection experiment with IL-9 into mouse T cells results in an autocrine loop and tumorigenesis of the transfected cells. These tumors share a number of similarities to Hodgkin's disease and large cell anaplastic lymphomas in human."} {"id": "PMID:1283280", "title": "[Epstein-Barr virus associated lymphocyte proliferation].", "content": "In recent years, techniques, probes, and reagents became available to reliably visualize individual Epstein-Barr virus (EBV)-infected cells, to assess EBV gene expression, and to analyze the clonal composition of EBV genomes in human tissues. Application of these techniques to more than 1000 lymphoid tissue specimens revealed (1) characteristic cellular and compartmental distribution patterns of EBV-infected cells in normal lymph nodes, reflecting the interference of EBV with physiologic B cell differentiation pathways, (2) an association of EBV with various mono- and oligoclonal lymphoproliferations ranging from benign conditions to overtly malignant lymphomas, and (3) characteristic patterns of EBV gene expression among EBV-associated lymphoproliferations. In the context of the established immortalizing and transforming properties of EBV, the findings support the concept of an etiologic role of EBV for cases of certain lymphomas such as Burkitt's lymphoma, anaplastic large cell lymphoma, Hodgkin's disease, and lymphomas arising in immunocompromised individuals. In contrast, lymphomas harboring EBV in only proportions of the tumor cells (such as cases of peripheral T cell lymphoma and some B cell lymphoma types) argue against an etiologic role in the primary process of malignant transformation for the virus in these instances. Since in many of these cases a proportion of the EBV infected tumor cells express the EBV oncoprotein LMP (latent membrane protein) the virus may influence, however, the proliferative properties as well as the morphological and molecular phenotype of the neoplastic cells.", "contents": "[Epstein-Barr virus associated lymphocyte proliferation]. In recent years, techniques, probes, and reagents became available to reliably visualize individual Epstein-Barr virus (EBV)-infected cells, to assess EBV gene expression, and to analyze the clonal composition of EBV genomes in human tissues. Application of these techniques to more than 1000 lymphoid tissue specimens revealed (1) characteristic cellular and compartmental distribution patterns of EBV-infected cells in normal lymph nodes, reflecting the interference of EBV with physiologic B cell differentiation pathways, (2) an association of EBV with various mono- and oligoclonal lymphoproliferations ranging from benign conditions to overtly malignant lymphomas, and (3) characteristic patterns of EBV gene expression among EBV-associated lymphoproliferations. In the context of the established immortalizing and transforming properties of EBV, the findings support the concept of an etiologic role of EBV for cases of certain lymphomas such as Burkitt's lymphoma, anaplastic large cell lymphoma, Hodgkin's disease, and lymphomas arising in immunocompromised individuals. In contrast, lymphomas harboring EBV in only proportions of the tumor cells (such as cases of peripheral T cell lymphoma and some B cell lymphoma types) argue against an etiologic role in the primary process of malignant transformation for the virus in these instances. Since in many of these cases a proportion of the EBV infected tumor cells express the EBV oncoprotein LMP (latent membrane protein) the virus may influence, however, the proliferative properties as well as the morphological and molecular phenotype of the neoplastic cells."} {"id": "PMID:1283281", "title": "[Autoimmune diseases and malignant lymphoma].", "content": "During the recent decade evidence accumulated, that autoantibodies exist with a high frequency in the normal B-cell repertoire. The autoreactive B-cell repertoire may undergo malignant transformation through the continuous challenge by autoantigen. Previous work on human paraproteins of plasmocytoma and immunocytoma has shown that a high proportion of paraproteins bind to self determinants. B-cell lymphoma may mimic the lesions in organotropic autoimmune disease, eg. Sj\u00f6gren's disease, Hashimoto's thyroiditis and coeliac disease by the neoplastic expansion of autoimmune receptors. Considerable evidence has been obtained, that the specific receptor interactions of the lymphoma with the autoantigen may be of functional significance. More precise knowledge on receptor specificities would permit new approaches to the understanding and manipulation of autoimmune disease and lymphoma.", "contents": "[Autoimmune diseases and malignant lymphoma]. During the recent decade evidence accumulated, that autoantibodies exist with a high frequency in the normal B-cell repertoire. The autoreactive B-cell repertoire may undergo malignant transformation through the continuous challenge by autoantigen. Previous work on human paraproteins of plasmocytoma and immunocytoma has shown that a high proportion of paraproteins bind to self determinants. B-cell lymphoma may mimic the lesions in organotropic autoimmune disease, eg. Sj\u00f6gren's disease, Hashimoto's thyroiditis and coeliac disease by the neoplastic expansion of autoimmune receptors. Considerable evidence has been obtained, that the specific receptor interactions of the lymphoma with the autoantigen may be of functional significance. More precise knowledge on receptor specificities would permit new approaches to the understanding and manipulation of autoimmune disease and lymphoma."} {"id": "PMID:1283282", "title": "Impairment of peripheral nervous system in patients with non-Hodgkin's lymphomas treated with CBVPM/AVBP and CHOP schedules.", "content": "Clinical examination and conduction velocity measurements in peripheral nerves have been done on 56 patients with non-Hodgkin's lymphomas of high malignancy (NHL). It is suggested that: the evaluation of the influence of chemotherapy on peripheral nervous system (PNS) is possible by means of systematic neurological and electroneurographic studies; electroneurographic assessment is most important in the diagnosis of early subclinical stages of peripheral neuropathy; toxic influence of CBVPM/AVBP protocol on PNS is greater than CHOP schedule; impairment of PNS due to chemotherapy is reversible in patients during complete remission (CR).", "contents": "Impairment of peripheral nervous system in patients with non-Hodgkin's lymphomas treated with CBVPM/AVBP and CHOP schedules. Clinical examination and conduction velocity measurements in peripheral nerves have been done on 56 patients with non-Hodgkin's lymphomas of high malignancy (NHL). It is suggested that: the evaluation of the influence of chemotherapy on peripheral nervous system (PNS) is possible by means of systematic neurological and electroneurographic studies; electroneurographic assessment is most important in the diagnosis of early subclinical stages of peripheral neuropathy; toxic influence of CBVPM/AVBP protocol on PNS is greater than CHOP schedule; impairment of PNS due to chemotherapy is reversible in patients during complete remission (CR)."} {"id": "PMID:1283283", "title": "Unusual case of granular lymphocytes (GL) proliferation: simultaneous reactive and neoplastic proliferation.", "content": "We report a case of a 55-year-old male with lymphoproliferative disease of granular lymphocytes. In the first year of follow-up reactive expansion of granular lymphocytes was observed during infectious episodes additionally to malignant proliferation. Histopathological studies revealed malignant lymphocytic infiltrations of the liver and gallbladder walls. The number of GL varied from 1.1 G/l to 17.8 G/l. Immunophenotyping studies showed surface phenotype CD3+, CD8+. There was markedly reduced NK cell function. The patient exhibited lack of severe parenchymal involvement, moderately increased white cell count (up to 21.0 G/l), severe neutropenia (0.06 G/l - 0.8 G/l) and recurrent infectious episodes.", "contents": "Unusual case of granular lymphocytes (GL) proliferation: simultaneous reactive and neoplastic proliferation. We report a case of a 55-year-old male with lymphoproliferative disease of granular lymphocytes. In the first year of follow-up reactive expansion of granular lymphocytes was observed during infectious episodes additionally to malignant proliferation. Histopathological studies revealed malignant lymphocytic infiltrations of the liver and gallbladder walls. The number of GL varied from 1.1 G/l to 17.8 G/l. Immunophenotyping studies showed surface phenotype CD3+, CD8+. There was markedly reduced NK cell function. The patient exhibited lack of severe parenchymal involvement, moderately increased white cell count (up to 21.0 G/l), severe neutropenia (0.06 G/l - 0.8 G/l) and recurrent infectious episodes."} {"id": "PMID:1283286", "title": "[Clinical course of hormone refractory cancer of the prostate].", "content": "Analysis of the clinical progression of 61 patients with prostate cancer undergoing hormone therapy. PSA allowed early detection in 86.9% cases. In 25 patients no rescue treatment was instituted, and 36 patients were treated with estramustine phosphate resulting in decreased PSA levels in 58% and objective response in 36%. Of these, 82% showed decreased PSA levels for over six months. Survival rate was higher in respondent, treated patients and comparable in non-respondents, treated versus non treated patients.", "contents": "[Clinical course of hormone refractory cancer of the prostate]. Analysis of the clinical progression of 61 patients with prostate cancer undergoing hormone therapy. PSA allowed early detection in 86.9% cases. In 25 patients no rescue treatment was instituted, and 36 patients were treated with estramustine phosphate resulting in decreased PSA levels in 58% and objective response in 36%. Of these, 82% showed decreased PSA levels for over six months. Survival rate was higher in respondent, treated patients and comparable in non-respondents, treated versus non treated patients."} {"id": "PMID:1283287", "title": "Familial occurrence of renal and M\u00fcllerian duct hypoplasia, craniofacial anomalies, severe growth and developmental delay.", "content": "Absence of the kidneys and of the M\u00fcllerian structures has been reported in many patients. We report on a brother and sister, born to nonconsanguineous parents, with renal hypoplasia, M\u00fcllerian duct hypoplasia, and strikingly similar facial abnormalities. Both sibs have severe growth and developmental retardation. We think that the unique clinical findings in these sibs represent a new syndrome. The embryological and genetic implications of this condition are discussed.", "contents": "Familial occurrence of renal and M\u00fcllerian duct hypoplasia, craniofacial anomalies, severe growth and developmental delay. Absence of the kidneys and of the M\u00fcllerian structures has been reported in many patients. We report on a brother and sister, born to nonconsanguineous parents, with renal hypoplasia, M\u00fcllerian duct hypoplasia, and strikingly similar facial abnormalities. Both sibs have severe growth and developmental retardation. We think that the unique clinical findings in these sibs represent a new syndrome. The embryological and genetic implications of this condition are discussed."} {"id": "PMID:1283288", "title": "Abnormal regulation of insulin-like growth factor gene expression in peripheral blood mononuclear cells from patients with IgA nephropathy.", "content": "We investigated insulin-like growth factor (IGF)-I and -II mRNA expression in peripheral blood mononuclear cells (PBMC) and T cells obtained from 31 patients with IgA nephropathy (IgAN), 43 patients with other types of glomerulonephritis and 16 health age-matched controls. The majority of patients with IgAN showed elevated IGF-I and -II mRNA expression in PBMC, while no IGF-I and -II mRNA expression was detected in PBMC obtained from patients with other types of glomerulonephritis or normal controls. In T cells obtained from IgAN, other types of glomerulonephritis and normal controls, however, IGF-I and -II mRNA expression was not detected. A positive correlation was noted between IGF-I and -II mRNA levels and urinary protein excretion. IGF-I and -II mRNA expression also correlated with the histopathological findings in the renal tissue of patients with IgAN. Sixty-nine percent of patients with more than 1.0 g/day proteinuria showed strong [more than (++)] IGF-I and -II mRNA expression in their PBMC. Eighty-one and 76% of patients with grade III and IV histopathological findings, respectively, showed strong IGF-I and -II gene expression in their PBMC. We also studied the clinical course of 11 patients with IgAN during hospitalization. The IGF-I and -II mRNA levels in these patients decreased gradually, as did proteinuria, after treatment. These studies suggest that abnormal regulation of IGF-I and -II gene expression in PBMC may be associated with the progression of IgAN and may be useful as an indicator of disease activity.", "contents": "Abnormal regulation of insulin-like growth factor gene expression in peripheral blood mononuclear cells from patients with IgA nephropathy. We investigated insulin-like growth factor (IGF)-I and -II mRNA expression in peripheral blood mononuclear cells (PBMC) and T cells obtained from 31 patients with IgA nephropathy (IgAN), 43 patients with other types of glomerulonephritis and 16 health age-matched controls. The majority of patients with IgAN showed elevated IGF-I and -II mRNA expression in PBMC, while no IGF-I and -II mRNA expression was detected in PBMC obtained from patients with other types of glomerulonephritis or normal controls. In T cells obtained from IgAN, other types of glomerulonephritis and normal controls, however, IGF-I and -II mRNA expression was not detected. A positive correlation was noted between IGF-I and -II mRNA levels and urinary protein excretion. IGF-I and -II mRNA expression also correlated with the histopathological findings in the renal tissue of patients with IgAN. Sixty-nine percent of patients with more than 1.0 g/day proteinuria showed strong [more than (++)] IGF-I and -II mRNA expression in their PBMC. Eighty-one and 76% of patients with grade III and IV histopathological findings, respectively, showed strong IGF-I and -II gene expression in their PBMC. We also studied the clinical course of 11 patients with IgAN during hospitalization. The IGF-I and -II mRNA levels in these patients decreased gradually, as did proteinuria, after treatment. These studies suggest that abnormal regulation of IGF-I and -II gene expression in PBMC may be associated with the progression of IgAN and may be useful as an indicator of disease activity."} {"id": "PMID:1283290", "title": "Method for the detection of glycopeptides at the picomole level in HPLC peptide maps.", "content": "Glycopeptide-containing fractions in HPLC peptide maps can be detected by a simple application of the microtiter plate-bound streptavidin-biotinylated glycopeptide-lectin method (M.-C. Shao, 1992, Anal. Biochem., 205, 77-82). To illustrate this application, the glycoproteins, ovalbumin and asialofetuin, reduced and S-alkylated with vinylpyridine, were digested with trypsin-L-1-p-tosylamino-2-phenylethylchloromethyl ketone and the tryptic peptides were fractionated by reverse-phase HPLC, monitoring for absorbance at 230 nm. Aliquots of the HPLC fractions (typically 0.2-0.5% of the total volume) were biotinylated and complexed with streptavidin in the wells of a microtiter plate, allowing the streptavidin-glycopeptide complex to adhere to the plate. Suitable lectins, such as concanavalin A, Datura stramonium agglutinin, and peanut agglutinin, all of which had been coupled to horse radish peroxidase, were added, and after thorough washing, only the wells containing streptavidin-bound glycopeptides retained the complementary lectin and gave a positive peroxidase reaction. Less than 1 pmol of glycopeptide can be detected. The demonstration that the glycopeptide detection could be inhibited either by addition of an excess of the appropriate sugar inhibitor to the different lectins or by digestion of the biotinylated glycopeptides with N-glycosidase F or O-glycosidase shows that the glycopeptide-lectin interaction is the basis for the reaction.", "contents": "Method for the detection of glycopeptides at the picomole level in HPLC peptide maps. Glycopeptide-containing fractions in HPLC peptide maps can be detected by a simple application of the microtiter plate-bound streptavidin-biotinylated glycopeptide-lectin method (M.-C. Shao, 1992, Anal. Biochem., 205, 77-82). To illustrate this application, the glycoproteins, ovalbumin and asialofetuin, reduced and S-alkylated with vinylpyridine, were digested with trypsin-L-1-p-tosylamino-2-phenylethylchloromethyl ketone and the tryptic peptides were fractionated by reverse-phase HPLC, monitoring for absorbance at 230 nm. Aliquots of the HPLC fractions (typically 0.2-0.5% of the total volume) were biotinylated and complexed with streptavidin in the wells of a microtiter plate, allowing the streptavidin-glycopeptide complex to adhere to the plate. Suitable lectins, such as concanavalin A, Datura stramonium agglutinin, and peanut agglutinin, all of which had been coupled to horse radish peroxidase, were added, and after thorough washing, only the wells containing streptavidin-bound glycopeptides retained the complementary lectin and gave a positive peroxidase reaction. Less than 1 pmol of glycopeptide can be detected. The demonstration that the glycopeptide detection could be inhibited either by addition of an excess of the appropriate sugar inhibitor to the different lectins or by digestion of the biotinylated glycopeptides with N-glycosidase F or O-glycosidase shows that the glycopeptide-lectin interaction is the basis for the reaction."} {"id": "PMID:1283291", "title": "Colorimetric quantitation of trace amounts of sodium lauryl sulfate in the presence of nucleic acids and proteins.", "content": "A fast and sensitive procedure for the colorimetric detection of sodium lauryl sulfate (SDS) is presented. The assay is based upon the formation of a chloroform-extractable ion pair between lauryl sulfate and methylene blue that is quantified spectrophotometrically with an estimated detection limit of 150 ng of SDS. The method is suitable for the monitoring of contaminating traces of SDS in protein or nucleic acid samples that have the potential to interfere with enzymatic manipulations such as proteolytic digest, restriction analysis, or reverse transcription. Since the procedure is extremely simple and no special equipment is required it is accessible to every researcher concerned with SDS contamination.", "contents": "Colorimetric quantitation of trace amounts of sodium lauryl sulfate in the presence of nucleic acids and proteins. A fast and sensitive procedure for the colorimetric detection of sodium lauryl sulfate (SDS) is presented. The assay is based upon the formation of a chloroform-extractable ion pair between lauryl sulfate and methylene blue that is quantified spectrophotometrically with an estimated detection limit of 150 ng of SDS. The method is suitable for the monitoring of contaminating traces of SDS in protein or nucleic acid samples that have the potential to interfere with enzymatic manipulations such as proteolytic digest, restriction analysis, or reverse transcription. Since the procedure is extremely simple and no special equipment is required it is accessible to every researcher concerned with SDS contamination."} {"id": "PMID:1283292", "title": "The active site titration of proteinases by using alpha 2-macroglobulin and high-performance liquid chromatography.", "content": "The active site titration for various proteinases relies on the development of optimal enzyme titrants for each proteinase, but these titrants are only available for a limited number of proteinases. We have described a new active site titration method applicable to various kinds of endoproteinases using small quantities of the enzymes. This method was carried out by using alpha 2-macroglobulin (alpha 2M) as a titrant and a high-performance liquid chromatography (HPLC) system. When the proteinase solution was treated with alpha 2M, the active proteinase was trapped by alpha 2M. In this reaction alpha 2M does not usually complex with inactive proteinase. After the reaction of proteinase with an excess of alpha 2M, the reaction mixture is applied to an HPLC gel column to separate the uncomplexed enzyme from the one complexed with alpha 2M. The active proteinase is complexed and eluted with alpha 2M, but the inactive proteinase is eluted at the original elution volume. The same amount of the enzyme was also applied to the column. From the decrease of the peak height at the elution position of the uncomplexed proteinase, we can estimate the ratio between enzymatically active proteinases and total proteinases. To test the usefulness of this method, we applied this method to chymotrypsin and trypsin whose activities were predetermined by conventional active site titration, and there was good agreement between both results. With this new method, we can estimate a proteinase activity with as little as 200 ng of the enzyme, a very small amount compared with those required in conventional methods.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "The active site titration of proteinases by using alpha 2-macroglobulin and high-performance liquid chromatography. The active site titration for various proteinases relies on the development of optimal enzyme titrants for each proteinase, but these titrants are only available for a limited number of proteinases. We have described a new active site titration method applicable to various kinds of endoproteinases using small quantities of the enzymes. This method was carried out by using alpha 2-macroglobulin (alpha 2M) as a titrant and a high-performance liquid chromatography (HPLC) system. When the proteinase solution was treated with alpha 2M, the active proteinase was trapped by alpha 2M. In this reaction alpha 2M does not usually complex with inactive proteinase. After the reaction of proteinase with an excess of alpha 2M, the reaction mixture is applied to an HPLC gel column to separate the uncomplexed enzyme from the one complexed with alpha 2M. The active proteinase is complexed and eluted with alpha 2M, but the inactive proteinase is eluted at the original elution volume. The same amount of the enzyme was also applied to the column. From the decrease of the peak height at the elution position of the uncomplexed proteinase, we can estimate the ratio between enzymatically active proteinases and total proteinases. To test the usefulness of this method, we applied this method to chymotrypsin and trypsin whose activities were predetermined by conventional active site titration, and there was good agreement between both results. With this new method, we can estimate a proteinase activity with as little as 200 ng of the enzyme, a very small amount compared with those required in conventional methods.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283293", "title": "Characterization of the glutamine synthetase amplifiable eukaryotic expression system applied to an integral membrane protein--the human thyrotropin receptor.", "content": "An amplifiable eukaryotic expression system, based upon glutamine synthetase, has been applied to the production of a complex integral membrane glycoprotein, the human receptor for the polypeptide hormone thyrotropin (TSH). Production of recombinant protein was achieved in chinese hamster ovary (CHO) cells at levels at least 10-fold higher than has been achieved in any other system. After amplification of the inserted gene, the gene copy number was found to be increased in most (but not all) subclones in the range of 3- to 50-fold; mRNA levels of the individual cell lines broadly followed their gene copy number. The level of protein production (measured both functionally and structurally, by radioligand binding and cytofluorimetry, respectively) also reflected these increases in DNA and RNA, but appeared to be limited to a maximum value which we conclude is the maximum that the cells can tolerate without impairing their viability. The receptor is efficiently coupled to adenylate cyclase (22-45 pM TSH producing a 50% response), although the coupling mechanism appeared to be saturated at higher receptor numbers. The high level of expression has allowed, for the first time, the detection of recombinant TSH receptor by immunochemical means. This expression system should prove very useful, not only in facilitating characterization of the TSH receptor, but also for the production of many other integral membrane proteins in their native form.", "contents": "Characterization of the glutamine synthetase amplifiable eukaryotic expression system applied to an integral membrane protein--the human thyrotropin receptor. An amplifiable eukaryotic expression system, based upon glutamine synthetase, has been applied to the production of a complex integral membrane glycoprotein, the human receptor for the polypeptide hormone thyrotropin (TSH). Production of recombinant protein was achieved in chinese hamster ovary (CHO) cells at levels at least 10-fold higher than has been achieved in any other system. After amplification of the inserted gene, the gene copy number was found to be increased in most (but not all) subclones in the range of 3- to 50-fold; mRNA levels of the individual cell lines broadly followed their gene copy number. The level of protein production (measured both functionally and structurally, by radioligand binding and cytofluorimetry, respectively) also reflected these increases in DNA and RNA, but appeared to be limited to a maximum value which we conclude is the maximum that the cells can tolerate without impairing their viability. The receptor is efficiently coupled to adenylate cyclase (22-45 pM TSH producing a 50% response), although the coupling mechanism appeared to be saturated at higher receptor numbers. The high level of expression has allowed, for the first time, the detection of recombinant TSH receptor by immunochemical means. This expression system should prove very useful, not only in facilitating characterization of the TSH receptor, but also for the production of many other integral membrane proteins in their native form."} {"id": "PMID:1283294", "title": "Effect of in vitro nitrogen dioxide exposure on human bronchial smooth muscle response.", "content": "The aim of this study was to develop an in vitro system in which an isolated bronchus from human lung was exposed, during 30 min, to a constant flow of either air or nitrogen dioxide (NO2), and to examine subsequently the contractile response of airway smooth muscle rings to carbachol, histamine, and substance P. Two proximal bronchi were mounted in an organ bath, perfused externally with Krebs-Henseleit solution and ventilated with clean air, 1.0 or 2.0 ppm NO2. The exposed bronchi were then cut into rings and mounted in a computerized organ bath system. Contractile responses to agonists were measured isometrically. In each ring, a cumulative concentration response curve was obtained to the desired agonist. We found that in vitro exposure of human lumen bronchus to a constant flow of air did not alter the contractility of the smooth muscle. Whereas in vitro exposure of the bronchus to 1.0 ppm NO2 did not significantly increase the efficacy or the potency of carbachol, exposure to 2.0 ppm NO2 increased airway smooth muscle contractions in response to carbachol, histamine, and substance P. These results indicate that our experimental preparation is well suited to study the respiratory toxicity of inhaled pollutants in order to understand further the mechanisms underlying toxicant-induced airway hyperresponsiveness.", "contents": "Effect of in vitro nitrogen dioxide exposure on human bronchial smooth muscle response. The aim of this study was to develop an in vitro system in which an isolated bronchus from human lung was exposed, during 30 min, to a constant flow of either air or nitrogen dioxide (NO2), and to examine subsequently the contractile response of airway smooth muscle rings to carbachol, histamine, and substance P. Two proximal bronchi were mounted in an organ bath, perfused externally with Krebs-Henseleit solution and ventilated with clean air, 1.0 or 2.0 ppm NO2. The exposed bronchi were then cut into rings and mounted in a computerized organ bath system. Contractile responses to agonists were measured isometrically. In each ring, a cumulative concentration response curve was obtained to the desired agonist. We found that in vitro exposure of human lumen bronchus to a constant flow of air did not alter the contractility of the smooth muscle. Whereas in vitro exposure of the bronchus to 1.0 ppm NO2 did not significantly increase the efficacy or the potency of carbachol, exposure to 2.0 ppm NO2 increased airway smooth muscle contractions in response to carbachol, histamine, and substance P. These results indicate that our experimental preparation is well suited to study the respiratory toxicity of inhaled pollutants in order to understand further the mechanisms underlying toxicant-induced airway hyperresponsiveness."} {"id": "PMID:1283295", "title": "Susceptibility of an emetine-resistant mutant of Entamoeba histolytica to multiple drugs and to channel blockers.", "content": "Previously a cloned emetine-resistant mutant of the protozoal parasite Entamoeba histolytica was shown to overexpress a gene for an ameba homolog of the mammalian P-glycoprotein, a plasma membrane pump that removes hydrophobic drugs from multidrug-resistant tumor cells. Three sets of experiments were performed to better characterize the multidrug-resistant phenotype of the emetine-resistant amebae. First, the emetine resistance of the mutant amebae was reversed by concentrations of calcium and sodium channel blockers effective in reversing drug resistance by multidrug-resistant tumor cells, but it was reversed only in the presence of very high concentrations of the tricyclic antidepressants. Second, the mutant amebae showed cross-resistance to antiamebic drugs used to treat luminal infection (iodoquinol and diloxanide) but were not cross-resistant to drugs used to treat invasive disease (chloroquine and metronidazole). Third, when amebae were loaded with radiolabeled emetine, the mutant parasites released the drug at approximately 1.6 times the rate of the wild-type organisms. We conclude that the emetine-resistant E. histolytica parasites have some but not all the features of the multidrug-resistant phenotype.", "contents": "Susceptibility of an emetine-resistant mutant of Entamoeba histolytica to multiple drugs and to channel blockers. Previously a cloned emetine-resistant mutant of the protozoal parasite Entamoeba histolytica was shown to overexpress a gene for an ameba homolog of the mammalian P-glycoprotein, a plasma membrane pump that removes hydrophobic drugs from multidrug-resistant tumor cells. Three sets of experiments were performed to better characterize the multidrug-resistant phenotype of the emetine-resistant amebae. First, the emetine resistance of the mutant amebae was reversed by concentrations of calcium and sodium channel blockers effective in reversing drug resistance by multidrug-resistant tumor cells, but it was reversed only in the presence of very high concentrations of the tricyclic antidepressants. Second, the mutant amebae showed cross-resistance to antiamebic drugs used to treat luminal infection (iodoquinol and diloxanide) but were not cross-resistant to drugs used to treat invasive disease (chloroquine and metronidazole). Third, when amebae were loaded with radiolabeled emetine, the mutant parasites released the drug at approximately 1.6 times the rate of the wild-type organisms. We conclude that the emetine-resistant E. histolytica parasites have some but not all the features of the multidrug-resistant phenotype."} {"id": "PMID:1283296", "title": "Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine.", "content": "2',3'-Dideoxy-5-fluoro-3'-thiacytidine (FTC) has been shown to be a potent and selective compound against human immunodeficiency virus type 1 in acutely infected primary human lymphocytes. FTC is also active against human immunodeficiency virus type 2, simian immunodeficiency virus, and feline immunodeficiency virus in various cell culture systems, including human monocytes. The antiviral activity can be prevented by 2'-deoxycytidine, but not by other natural nucleosides, suggesting that FTC must be phosphorylated to be active and 2'-deoxycytidine kinase is responsible for the phosphorylation. By using chiral columns or enzymatic techniques, the two enantiomers of FTC were separated. The (-)-beta-enantiomer of FTC was about 20-fold more potent than the (+)-beta-enantiomer against human immunodeficiency virus type 1 in peripheral blood mononuclear cells and was also effective in thymidine kinase-deficient CEM cells. Racemic FTC and its enantiomers were nontoxic to human lymphocytes and other cell lines at concentrations of up to 100 microM. Studies with human bone marrow cells indicated that racemic FTC and its (-)-enantiomer had a median inhibitory concentration of > 30 microM. The (+)-enantiomer was significantly more toxic than the (-)-enantiomer to myeloid progenitor cells. The susceptibilities to FTC of pretherapy isolates in comparison with those of posttherapy 3'-azido-3'-deoxythymidine-resistant viruses in human lymphocytes were not substantially different. Similar results were obtained with well-defined 2',3'-dideoxyinosine- and nevirapine-resistant viruses. (-)-FTC-5'-triphosphate competitively inhibited human immunodeficiency virus type 1 reverse transcriptase, with an inhibition constant of 2.9 microM, when a poly(I)n.oligo(dC)19-24 template primer was used. These results suggest that further development of the (-)-Beta-enantiomer of FTC is warranted as an antiviral agent for infections caused by human immunodeficiency viruses.", "contents": "Selective inhibition of human immunodeficiency viruses by racemates and enantiomers of cis-5-fluoro-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine. 2',3'-Dideoxy-5-fluoro-3'-thiacytidine (FTC) has been shown to be a potent and selective compound against human immunodeficiency virus type 1 in acutely infected primary human lymphocytes. FTC is also active against human immunodeficiency virus type 2, simian immunodeficiency virus, and feline immunodeficiency virus in various cell culture systems, including human monocytes. The antiviral activity can be prevented by 2'-deoxycytidine, but not by other natural nucleosides, suggesting that FTC must be phosphorylated to be active and 2'-deoxycytidine kinase is responsible for the phosphorylation. By using chiral columns or enzymatic techniques, the two enantiomers of FTC were separated. The (-)-beta-enantiomer of FTC was about 20-fold more potent than the (+)-beta-enantiomer against human immunodeficiency virus type 1 in peripheral blood mononuclear cells and was also effective in thymidine kinase-deficient CEM cells. Racemic FTC and its enantiomers were nontoxic to human lymphocytes and other cell lines at concentrations of up to 100 microM. Studies with human bone marrow cells indicated that racemic FTC and its (-)-enantiomer had a median inhibitory concentration of > 30 microM. The (+)-enantiomer was significantly more toxic than the (-)-enantiomer to myeloid progenitor cells. The susceptibilities to FTC of pretherapy isolates in comparison with those of posttherapy 3'-azido-3'-deoxythymidine-resistant viruses in human lymphocytes were not substantially different. Similar results were obtained with well-defined 2',3'-dideoxyinosine- and nevirapine-resistant viruses. (-)-FTC-5'-triphosphate competitively inhibited human immunodeficiency virus type 1 reverse transcriptase, with an inhibition constant of 2.9 microM, when a poly(I)n.oligo(dC)19-24 template primer was used. These results suggest that further development of the (-)-Beta-enantiomer of FTC is warranted as an antiviral agent for infections caused by human immunodeficiency viruses."} {"id": "PMID:1283297", "title": "Lesions and preferential initial localization of [S-methyl-3H]bleomycin A2 on Saccharomyces cerevisiae cell walls and membranes.", "content": "Extensive lesions were produced in cell walls of Saccharomyces cerevisiae by the bleomycin family of anticancer antibiotics (30 min to 4 h). Electron micrographs revealed that the alterations were most frequently large breaks and small interruptions or holes in cell walls, which sometimes extended into cell membranes. Large portions of cell walls were sometimes lost. Cell walls were frequently ruptured in one or more positions. More than 75% of bud scar regions in single-plane sections and all bud scars in serial sections exhibited many interruptions and breaks after 3 or 4 h of treatment. The discovery of extensive damage to cell walls was consistent with the preferential (approximately 70%) association of radiolabeled bleomycin with cell walls and perimeters of bud scar regions after short exposures (30 min). After longer exposures, the distribution of silver grains changed from a predominant association with cell walls (30 min) to an increased association with the cell cytoplasm (1 to 4 h). This correlated with increased ultrastructural damage, since damage to cell walls was generally more frequent and more severe with increasing length of treatment (30 min to 4 h) or dose (25 to 100 micrograms/ml). Although DNA lesions are believed to be the lethal properties of bleomycins, the lesions produced in cell walls are also lethal properties of the antibiotics. The distributions of lesions on cell walls suggested a generalized interaction of the antibiotic with a cell wall component. These results led us to hypothesize a mechanism of effective antifungal action for the bleomycin family of antibiotics.", "contents": "Lesions and preferential initial localization of [S-methyl-3H]bleomycin A2 on Saccharomyces cerevisiae cell walls and membranes. Extensive lesions were produced in cell walls of Saccharomyces cerevisiae by the bleomycin family of anticancer antibiotics (30 min to 4 h). Electron micrographs revealed that the alterations were most frequently large breaks and small interruptions or holes in cell walls, which sometimes extended into cell membranes. Large portions of cell walls were sometimes lost. Cell walls were frequently ruptured in one or more positions. More than 75% of bud scar regions in single-plane sections and all bud scars in serial sections exhibited many interruptions and breaks after 3 or 4 h of treatment. The discovery of extensive damage to cell walls was consistent with the preferential (approximately 70%) association of radiolabeled bleomycin with cell walls and perimeters of bud scar regions after short exposures (30 min). After longer exposures, the distribution of silver grains changed from a predominant association with cell walls (30 min) to an increased association with the cell cytoplasm (1 to 4 h). This correlated with increased ultrastructural damage, since damage to cell walls was generally more frequent and more severe with increasing length of treatment (30 min to 4 h) or dose (25 to 100 micrograms/ml). Although DNA lesions are believed to be the lethal properties of bleomycins, the lesions produced in cell walls are also lethal properties of the antibiotics. The distributions of lesions on cell walls suggested a generalized interaction of the antibiotic with a cell wall component. These results led us to hypothesize a mechanism of effective antifungal action for the bleomycin family of antibiotics."} {"id": "PMID:1283298", "title": "Familial pancreatic enzyme insufficiency.", "content": "A father and son with profound reduction of exocrine pancreatic activity and little visible pancreatic tissue on ultrasound or computed tomography are described. Both have some degree of liver disease, which is more marked in the son. The disorder, apparently familial, does not correspond to any reported previously.", "contents": "Familial pancreatic enzyme insufficiency. A father and son with profound reduction of exocrine pancreatic activity and little visible pancreatic tissue on ultrasound or computed tomography are described. Both have some degree of liver disease, which is more marked in the son. The disorder, apparently familial, does not correspond to any reported previously."} {"id": "PMID:1283299", "title": "[Tissue reactions in children treated with hemodynamic dextran and detoxication polyvinylpyrrolidone plasma substitutes].", "content": "By means of light and electron microscopy tissue reactions produced by repeated use of polyvinylpyrrolidone (PVP) and dextran plasma substitutes are studied on the material of 20 autopsies and 4 biopsies as well as in 65 experimental cases. Delayed type of PVP accumulation in tissues after the hemodes administration is determined as well as its dependence on the dose, time, kidney function and the presence of inflammatory foci. The differences in tissue reactions after administration of dextran and PVP substitutes are established. The results indicate that medicinal thesaurismosis may develop only after repeated infusions of PVP substitutes, while dextran accumulation is of a transitory type and results in characteristic morphological changes in the renal epithelium only.", "contents": "[Tissue reactions in children treated with hemodynamic dextran and detoxication polyvinylpyrrolidone plasma substitutes]. By means of light and electron microscopy tissue reactions produced by repeated use of polyvinylpyrrolidone (PVP) and dextran plasma substitutes are studied on the material of 20 autopsies and 4 biopsies as well as in 65 experimental cases. Delayed type of PVP accumulation in tissues after the hemodes administration is determined as well as its dependence on the dose, time, kidney function and the presence of inflammatory foci. The differences in tissue reactions after administration of dextran and PVP substitutes are established. The results indicate that medicinal thesaurismosis may develop only after repeated infusions of PVP substitutes, while dextran accumulation is of a transitory type and results in characteristic morphological changes in the renal epithelium only."} {"id": "PMID:1283300", "title": "Characterization and epitope mapping of human monoclonal antibodies to PDC-E2, the immunodominant autoantigen of primary biliary cirrhosis.", "content": "Further to define the epitopes of PDC-E2, the major autoantigen in primary biliary cirrhosis (PBC), we have developed and characterized five human monoclonal antibodies. These antibodies were derived by fusing a regional hepatic lymph node from a patient with PBC with the mouse human heterohybrid cell line F3B6. Previous studies of epitope mapping of PDC-E2 have relied on whole sera and have suggested that the immunodominant epitope lies within the inner lipoyl domain of the molecule. However, selective absorption studies using whole sera and a series of overlapping recombinant peptides of PDC-E2 have suggested that the epitope may also include a large conformational component. Moreover, several laboratories have suggested that autoantibodies against the 2-oxo acids dehydrogenase autoantigens are cross-reactive. The five monoclonal antibodies generated included three IgG2a and two IgM antibodies and were studied for antigen specificity using recombinant PDC-E2, recombinant BCKD-E2, histone, dsDNA, IgG (Fc), collagen and a recombinant irrelevant liver specific control, the F alloantigen. The antibodies were also used to probe blots of human, bovine, mouse and rat mitochondria. Finally, fine specificity was studied by selective ELISA and absorption against overlapping expressing fragments of PDC-E2. All five monoclonals, but none of the other mitochondrial autoantigens were specific for PDC-E2. In fact, although affinity purified antibodies to PDC-E2 from patients with PBC cross-reacted with protein X, the human monoclonals did not, suggesting that protein X contains an epitope distinct from that found on PDC-E2. Additionally, all three IgG2 monoclonals recognized distinct epitopes within the inner lipoyl domain of PDC-E2.", "contents": "Characterization and epitope mapping of human monoclonal antibodies to PDC-E2, the immunodominant autoantigen of primary biliary cirrhosis. Further to define the epitopes of PDC-E2, the major autoantigen in primary biliary cirrhosis (PBC), we have developed and characterized five human monoclonal antibodies. These antibodies were derived by fusing a regional hepatic lymph node from a patient with PBC with the mouse human heterohybrid cell line F3B6. Previous studies of epitope mapping of PDC-E2 have relied on whole sera and have suggested that the immunodominant epitope lies within the inner lipoyl domain of the molecule. However, selective absorption studies using whole sera and a series of overlapping recombinant peptides of PDC-E2 have suggested that the epitope may also include a large conformational component. Moreover, several laboratories have suggested that autoantibodies against the 2-oxo acids dehydrogenase autoantigens are cross-reactive. The five monoclonal antibodies generated included three IgG2a and two IgM antibodies and were studied for antigen specificity using recombinant PDC-E2, recombinant BCKD-E2, histone, dsDNA, IgG (Fc), collagen and a recombinant irrelevant liver specific control, the F alloantigen. The antibodies were also used to probe blots of human, bovine, mouse and rat mitochondria. Finally, fine specificity was studied by selective ELISA and absorption against overlapping expressing fragments of PDC-E2. All five monoclonals, but none of the other mitochondrial autoantigens were specific for PDC-E2. In fact, although affinity purified antibodies to PDC-E2 from patients with PBC cross-reacted with protein X, the human monoclonals did not, suggesting that protein X contains an epitope distinct from that found on PDC-E2. Additionally, all three IgG2 monoclonals recognized distinct epitopes within the inner lipoyl domain of PDC-E2."} {"id": "PMID:1283301", "title": "Anti-peripheral nerve antibodies in leprosy patients recognize an epitope shared by the M. leprae 65 kDa heat shock protein.", "content": "Binding of leprosy sera to peripheral nerve from different species (mouse, guinea pig and rabbit) was evaluated by ELISA. A majority of sera, whatever the clinical form of leprosy, bind to these antigens. Absorption with Mycobacterium bovis BCG demonstrated that these antibodies recognize cross-reactive epitopes between peripheral nerve and mycobacteria. In immunoblot analysis, both leprosy patient sera and a monoclonal antibody directed at the 65 kDa heat shock protein of M. leprae were shown to react with a heat-shock 67-68 kDa sciatic nerve protein. Binding of the monoclonal antibody to this sciatic nerve antigen was prevented by incubation with lepromatous patient sera, showing that some peripheral nerve epitopes recognized by patient antibodies are shared by the 65 kDa heat shock protein of M. leprae.", "contents": "Anti-peripheral nerve antibodies in leprosy patients recognize an epitope shared by the M. leprae 65 kDa heat shock protein. Binding of leprosy sera to peripheral nerve from different species (mouse, guinea pig and rabbit) was evaluated by ELISA. A majority of sera, whatever the clinical form of leprosy, bind to these antigens. Absorption with Mycobacterium bovis BCG demonstrated that these antibodies recognize cross-reactive epitopes between peripheral nerve and mycobacteria. In immunoblot analysis, both leprosy patient sera and a monoclonal antibody directed at the 65 kDa heat shock protein of M. leprae were shown to react with a heat-shock 67-68 kDa sciatic nerve protein. Binding of the monoclonal antibody to this sciatic nerve antigen was prevented by incubation with lepromatous patient sera, showing that some peripheral nerve epitopes recognized by patient antibodies are shared by the 65 kDa heat shock protein of M. leprae."} {"id": "PMID:1283302", "title": "Assaying glycoprotein hormones--the influence of glycosylation on immunoreactivity.", "content": "The epitopes of the human glycoprotein hormones (follicle-stimulating hormone [hFSH], luteinizing hormone [hLH], chorionic gonadotrophin [hCG], thyroid-stimulating hormone [hTSH] and erythropoietin [hEPO]) appear to consist only of peptide components. Their interactions with antibodies, however, are influenced by their bulky and often highly charged carbohydrate moieties. Thus, isoforms of these hormones (the majority of which are glycoforms) differ in their specific immunoreactivities as well as in their specific in vivo and in vitro bioactivities. This can create difficulties for the standardization of immunoassays as the isoform composition of a hormone depends both on its source and method of isolation.", "contents": "Assaying glycoprotein hormones--the influence of glycosylation on immunoreactivity. The epitopes of the human glycoprotein hormones (follicle-stimulating hormone [hFSH], luteinizing hormone [hLH], chorionic gonadotrophin [hCG], thyroid-stimulating hormone [hTSH] and erythropoietin [hEPO]) appear to consist only of peptide components. Their interactions with antibodies, however, are influenced by their bulky and often highly charged carbohydrate moieties. Thus, isoforms of these hormones (the majority of which are glycoforms) differ in their specific immunoreactivities as well as in their specific in vivo and in vitro bioactivities. This can create difficulties for the standardization of immunoassays as the isoform composition of a hormone depends both on its source and method of isolation."} {"id": "PMID:1283303", "title": "Neurite regeneration in the cat recurrent laryngeal nerve: an immunohistochemical study.", "content": "The recurrent laryngeal nerve (RLN) consists of various motor, sensory and autonomic nerve fibers, although it has not been established whether different neuronal types exhibit a similar ability to regenerate. To address this question, freezing was used to injure the cat RLN fibers and the presence or absence of immunoreactivity for neuropeptides or transmitter-synthesizing enzymes was then examined as a marker to classify the fibers. In the control RLN, calcitonin gene-related peptide-immunoreactive (CGRP-IR) fibers were the highest in number and were distributed throughout the nerve fascicles. The number of substance P-immunoreactive (SP-IR) fibers was about 40% that of CGRP-IR fibers, while a portion of CGRP-IR fibers was found to contain SP immunoreactivity. Relatively low numbers of tyrosine hydroxylase-immunoreactive (TH-IR) and neuropeptide Y (NPY-IR) nerve fibers were seen which tended to form clusters. The distribution pattern of NPY-IR fibers was very similar to that of TH-IR fibers. In the regenerating RLN 1 week after the freezing injury, the fastest growing axons were CGRP-IR, while the regenerating rates of SP-IR, TH-IR and NPY-IR fibers were slower than that of CGRP-IR fibers. These results suggest that the ability for neurite regeneration varies among neuron types and that CGRP-IR fibers possess the most rapid ability to regenerate.", "contents": "Neurite regeneration in the cat recurrent laryngeal nerve: an immunohistochemical study. The recurrent laryngeal nerve (RLN) consists of various motor, sensory and autonomic nerve fibers, although it has not been established whether different neuronal types exhibit a similar ability to regenerate. To address this question, freezing was used to injure the cat RLN fibers and the presence or absence of immunoreactivity for neuropeptides or transmitter-synthesizing enzymes was then examined as a marker to classify the fibers. In the control RLN, calcitonin gene-related peptide-immunoreactive (CGRP-IR) fibers were the highest in number and were distributed throughout the nerve fascicles. The number of substance P-immunoreactive (SP-IR) fibers was about 40% that of CGRP-IR fibers, while a portion of CGRP-IR fibers was found to contain SP immunoreactivity. Relatively low numbers of tyrosine hydroxylase-immunoreactive (TH-IR) and neuropeptide Y (NPY-IR) nerve fibers were seen which tended to form clusters. The distribution pattern of NPY-IR fibers was very similar to that of TH-IR fibers. In the regenerating RLN 1 week after the freezing injury, the fastest growing axons were CGRP-IR, while the regenerating rates of SP-IR, TH-IR and NPY-IR fibers were slower than that of CGRP-IR fibers. These results suggest that the ability for neurite regeneration varies among neuron types and that CGRP-IR fibers possess the most rapid ability to regenerate."} {"id": "PMID:1283304", "title": "A re-evaluation of the classification of olfactory epithelia in patients with olfactory disorders.", "content": "We have previously demonstrated that human olfactory epithelia can be classified into five grades according to the degree of degeneration present in patients with various kinds of olfactory disorders. In practice, however, the occurrence of additional types of cell changes in other kinds of olfactory disorders and findings with immunohistochemical techniques have led us to re-evaluate our previous classification. In the present study, changes in olfactory epithelia from ten patients with various kinds of olfactory disorders are discussed and a revised classification is proposed. Microvillar and differentiating cells were also evaluated in the epithelium studied.", "contents": "A re-evaluation of the classification of olfactory epithelia in patients with olfactory disorders. We have previously demonstrated that human olfactory epithelia can be classified into five grades according to the degree of degeneration present in patients with various kinds of olfactory disorders. In practice, however, the occurrence of additional types of cell changes in other kinds of olfactory disorders and findings with immunohistochemical techniques have led us to re-evaluate our previous classification. In the present study, changes in olfactory epithelia from ten patients with various kinds of olfactory disorders are discussed and a revised classification is proposed. Microvillar and differentiating cells were also evaluated in the epithelium studied."} {"id": "PMID:1283305", "title": "Chemosensitivity of head and neck cancer with the rapid thymidine incorporation assay and its clinical application.", "content": "The chemosensitivity of various head and neck cancers was investigated with the 5-day rapid thymidine incorporation assay in soft agar culture. The evaluability rate was 56%. Head and neck cancers were sensitive in vitro, in decreasing order, to peplomycin, cisplatin, bleomycin, 5-fluorouracil, mitomycin C, and doxorubicin. Primary tumors and neck metastases exhibited the same sensitivity, with 21% of all specimens tested responding. In vitro chemosensitivities were similar among patients younger than 69 years of age and those older than 70. The predictive accuracy for sensitivity tested prospectively in five cases was 80% and that for resistance in four was 75%.", "contents": "Chemosensitivity of head and neck cancer with the rapid thymidine incorporation assay and its clinical application. The chemosensitivity of various head and neck cancers was investigated with the 5-day rapid thymidine incorporation assay in soft agar culture. The evaluability rate was 56%. Head and neck cancers were sensitive in vitro, in decreasing order, to peplomycin, cisplatin, bleomycin, 5-fluorouracil, mitomycin C, and doxorubicin. Primary tumors and neck metastases exhibited the same sensitivity, with 21% of all specimens tested responding. In vitro chemosensitivities were similar among patients younger than 69 years of age and those older than 70. The predictive accuracy for sensitivity tested prospectively in five cases was 80% and that for resistance in four was 75%."} {"id": "PMID:1283306", "title": "Cytoplasmic bridges and gap junctions in an insect cell line (Aedes albopictus).", "content": "Cell pairs of an insect cell line (Aedes albopictus, clone C6/36) were used study simultaneously the diffusional and electrical properties of intercellular junctions. Diffusion studies involved injection of fluorescent molecules into one cell of a cell pair and visual inspection of their intercellular redistribution. Electrical measurements involved a dual voltage clamp method and whole-cell recording with patch pipette. The voltage clamp protocol was aimed at examining the dependency of the junctional conductance, gj, on membrane potential, Vm. Cell pairs exhibiting a voltage-dependent gj were found to allow intercellular diffusion of Lucifer Yellow CH (molecular mass, 443 Da), but not of FITC-dextran (molecular mass, 4,400 Da). This response pattern is consistent with the presence of gap junctions in the intercellular junctions. Cell pairs showing no voltage dependence of gj were found to permit intercellular diffusion of both Lucifer Yellow CH and FITC-dextran (dextran labelled with fluorescein isothiocyanate). This behaviour is compatible with the presence of cytoplasmic bridges connecting the two adjacent cells. Hence, in culture the cells investigated express two kinds of intercellular structures, gap junctions and cytoplasmic bridges.", "contents": "Cytoplasmic bridges and gap junctions in an insect cell line (Aedes albopictus). Cell pairs of an insect cell line (Aedes albopictus, clone C6/36) were used study simultaneously the diffusional and electrical properties of intercellular junctions. Diffusion studies involved injection of fluorescent molecules into one cell of a cell pair and visual inspection of their intercellular redistribution. Electrical measurements involved a dual voltage clamp method and whole-cell recording with patch pipette. The voltage clamp protocol was aimed at examining the dependency of the junctional conductance, gj, on membrane potential, Vm. Cell pairs exhibiting a voltage-dependent gj were found to allow intercellular diffusion of Lucifer Yellow CH (molecular mass, 443 Da), but not of FITC-dextran (molecular mass, 4,400 Da). This response pattern is consistent with the presence of gap junctions in the intercellular junctions. Cell pairs showing no voltage dependence of gj were found to permit intercellular diffusion of both Lucifer Yellow CH and FITC-dextran (dextran labelled with fluorescein isothiocyanate). This behaviour is compatible with the presence of cytoplasmic bridges connecting the two adjacent cells. Hence, in culture the cells investigated express two kinds of intercellular structures, gap junctions and cytoplasmic bridges."} {"id": "PMID:1283307", "title": "Failure of c-myc gene expression in B cells of some patients with common variable immunodeficiencies.", "content": "Many reports have shown that expression of the c-myc protooncogene represents an early event of lymphocyte activation. Calcium influx and activation of protein kinase C synergistically bypass the early signal transduction of lymphocyte activation. In this study, the c-myc message of B cells or B cell lines stimulated by 12-o-tetradecanoylphorbol-13-acetate (TPA), A23187, Staphylococcus aureus Cowan I (SAC), or anti-mu was not expressed or was poorly expressed in common variable immunodeficiency (CVID) patients whose B cells did not differentiate or only poorly differentiated to SAC plus recombinant interleukin 2, whereas the c-myc message of 1 CVID patient's B cells that differentiated well in IgM secretion to SAC plus recombinant interleukin 2 was well expressed when stimulated by TPA, A23187, SAC, or anti-mu. These results suggest that an abnormality exists in the early signal transduction process on some CVID patients' B cells and that it may be in the bypass by calcium influx and direct activation of protein kinase C.", "contents": "Failure of c-myc gene expression in B cells of some patients with common variable immunodeficiencies. Many reports have shown that expression of the c-myc protooncogene represents an early event of lymphocyte activation. Calcium influx and activation of protein kinase C synergistically bypass the early signal transduction of lymphocyte activation. In this study, the c-myc message of B cells or B cell lines stimulated by 12-o-tetradecanoylphorbol-13-acetate (TPA), A23187, Staphylococcus aureus Cowan I (SAC), or anti-mu was not expressed or was poorly expressed in common variable immunodeficiency (CVID) patients whose B cells did not differentiate or only poorly differentiated to SAC plus recombinant interleukin 2, whereas the c-myc message of 1 CVID patient's B cells that differentiated well in IgM secretion to SAC plus recombinant interleukin 2 was well expressed when stimulated by TPA, A23187, SAC, or anti-mu. These results suggest that an abnormality exists in the early signal transduction process on some CVID patients' B cells and that it may be in the bypass by calcium influx and direct activation of protein kinase C."} {"id": "PMID:1283308", "title": "Monoclonal antibodies to the extracellular domain of HIV-1IIIB gp160 that neutralize infectivity, block binding to CD4, and react with diverse isolates.", "content": "Ten monoclonal antibodies prepared against a soluble, recombinant form of gp160, derived from the IIIB isolate of HIV-1, were characterized. Four of the antibodies neutralized HIV-1IIIB infectivity in vitro, three blocked the binding of recombinant gp120 to CD4, three were reactive with gp41, and one preferentially reacted with an epitope on gp120 within the gp160 precursor. All three CD4 blocking antibodies bound to distinct epitopes, with one mapping to the C1 domain, one mapping to the C4 domain, and one reactive with a conformation-dependent, discontinuous epitope. Of these, the antibody reactive with the discontinuous epitope exhibited neutralizing activity against homologous and heterologous strains of HIV-1. The binding of these monoclonal antibodies to a panel of seven recombinant gp120s prepared from diverse isolates of HIV-1 was measured, and monoclonal antibodies with broad cross reactivity were identified. The epitopes recognized by 7 of the 10 monoclonal antibodies studied were localized by their reactivity with synthetic peptides and with fragments of gp120 expressed as fusion proteins in a lambda gt-11 gp160 epitope library.", "contents": "Monoclonal antibodies to the extracellular domain of HIV-1IIIB gp160 that neutralize infectivity, block binding to CD4, and react with diverse isolates. Ten monoclonal antibodies prepared against a soluble, recombinant form of gp160, derived from the IIIB isolate of HIV-1, were characterized. Four of the antibodies neutralized HIV-1IIIB infectivity in vitro, three blocked the binding of recombinant gp120 to CD4, three were reactive with gp41, and one preferentially reacted with an epitope on gp120 within the gp160 precursor. All three CD4 blocking antibodies bound to distinct epitopes, with one mapping to the C1 domain, one mapping to the C4 domain, and one reactive with a conformation-dependent, discontinuous epitope. Of these, the antibody reactive with the discontinuous epitope exhibited neutralizing activity against homologous and heterologous strains of HIV-1. The binding of these monoclonal antibodies to a panel of seven recombinant gp120s prepared from diverse isolates of HIV-1 was measured, and monoclonal antibodies with broad cross reactivity were identified. The epitopes recognized by 7 of the 10 monoclonal antibodies studied were localized by their reactivity with synthetic peptides and with fragments of gp120 expressed as fusion proteins in a lambda gt-11 gp160 epitope library."} {"id": "PMID:1283309", "title": "Inactivation of the human immunodeficiency virus by hypericin: evidence for photochemical alterations of p24 and a block in uncoating.", "content": "Following attachment and entry of human immunodeficiency virus (HIV) into a host cell, the HIV genomic RNA is reverse transcribed to cDNA. This step may be inhibited by hypericin, a compound that induces alterations of the retroviral capsid. Incubation of HIV with hypericin rendered the virus noninfectious. The replication of HIV was blocked early; HIV cDNA could not be detected in cells challenged with hypericin-treated HIV. Hypericin did not inhibit the binding of recombinant gp120 to CD4+ cells, nor did hypericin inhibit syncytium formation. However, reverse transcriptase activity could not be released from hypericin-treated virions. Western blot analysis revealed altered mobility of the HIV major capsid protein (p24) following hypericin treatment. Hypericin-treated recombinant HIV p24 exhibited similar altered mobility. The inactivation of HIV infectivity and the alterations in p24 mobility required hypericin incubations in the presence of visible light. Collectively, these data suggest that photochemical alterations of the HIV capsid may contribute to the hypericin-mediated inactivation of HIV. Such alterations may inhibit the release of RT activity from treated HIV, and prevent uncoating and subsequent reverse transcription of the HIV genome within a target cell.", "contents": "Inactivation of the human immunodeficiency virus by hypericin: evidence for photochemical alterations of p24 and a block in uncoating. Following attachment and entry of human immunodeficiency virus (HIV) into a host cell, the HIV genomic RNA is reverse transcribed to cDNA. This step may be inhibited by hypericin, a compound that induces alterations of the retroviral capsid. Incubation of HIV with hypericin rendered the virus noninfectious. The replication of HIV was blocked early; HIV cDNA could not be detected in cells challenged with hypericin-treated HIV. Hypericin did not inhibit the binding of recombinant gp120 to CD4+ cells, nor did hypericin inhibit syncytium formation. However, reverse transcriptase activity could not be released from hypericin-treated virions. Western blot analysis revealed altered mobility of the HIV major capsid protein (p24) following hypericin treatment. Hypericin-treated recombinant HIV p24 exhibited similar altered mobility. The inactivation of HIV infectivity and the alterations in p24 mobility required hypericin incubations in the presence of visible light. Collectively, these data suggest that photochemical alterations of the HIV capsid may contribute to the hypericin-mediated inactivation of HIV. Such alterations may inhibit the release of RT activity from treated HIV, and prevent uncoating and subsequent reverse transcription of the HIV genome within a target cell."} {"id": "PMID:1283310", "title": "HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri.", "content": "An aqueous extract of Phyllanthus niruri (Euphorbiaceae) inhibited human immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT). The inhibitor against HIV-1-RT in this plant was purified by combination of three column chromatographies, Sephadex LH-20, cellulose, and reverse-phase high-performance liquid chromatography. The inhibitor was then identified by nuclear magnetic resonance (NMR) spectra as repandusinic acid A monosodium salt (RA) which was originally isolated from Mallotus repandus. The 50% inhibitory doses (ID50) of RA on HIV-1-RT and DNA polymerase alpha (from HeLa cells) were 0.05 microM and 0.6 microM, respectively, representing approximately a 10-fold more sensitivity of HIV-1-RT compared with DNA polymerase alpha. RA was shown to be a competitive inhibitor with respect to the template-primer while it was a noncompetitive inhibitor with respect to the substrate. RA as low as 10.1 microM inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In addition, 4.5 microM of RA inhibited HIV-1-induced giant cell formation of SUP-T1 approximately 50%. RA (2.5 microM) inhibited up to 90% of HIV-1 specific p24 antigen production in a Clone H9 cell system.", "contents": "HIV-1 reverse transcriptase inhibitor from Phyllanthus niruri. An aqueous extract of Phyllanthus niruri (Euphorbiaceae) inhibited human immunodeficiency virus type-1 reverse transcriptase (HIV-1-RT). The inhibitor against HIV-1-RT in this plant was purified by combination of three column chromatographies, Sephadex LH-20, cellulose, and reverse-phase high-performance liquid chromatography. The inhibitor was then identified by nuclear magnetic resonance (NMR) spectra as repandusinic acid A monosodium salt (RA) which was originally isolated from Mallotus repandus. The 50% inhibitory doses (ID50) of RA on HIV-1-RT and DNA polymerase alpha (from HeLa cells) were 0.05 microM and 0.6 microM, respectively, representing approximately a 10-fold more sensitivity of HIV-1-RT compared with DNA polymerase alpha. RA was shown to be a competitive inhibitor with respect to the template-primer while it was a noncompetitive inhibitor with respect to the substrate. RA as low as 10.1 microM inhibited HIV-1-induced cytopathogenicity in MT-4 cells. In addition, 4.5 microM of RA inhibited HIV-1-induced giant cell formation of SUP-T1 approximately 50%. RA (2.5 microM) inhibited up to 90% of HIV-1 specific p24 antigen production in a Clone H9 cell system."} {"id": "PMID:1283311", "title": "Dissociation between early loss of actin fibres and subsequent cell death in serum-deprived quiescent Balb/c-3T3 cells.", "content": "Serum withdrawal from either growing or quiescent Balb/c-3T3 murine fibroblasts causes a loss of F-actin fibres and focal adhesions within 30 min. Cells that are growing survive serum deprivation, whereas the great majority of density-arrested quiescent cells die during a period of up to 5 h from serum withdrawal. During this time an approximately constant fraction of the quiescent cell population dies per unit time. The population half-life is 60-70 min during this time. Addition of an appropriate cell growth factor or second messenger agonist at the time of serum withdrawal or within 2 h after serum withdrawal protects a similar fraction of viable cells. These findings suggest a model according to which withdrawal of serum (i.e. growth factors) initiates the death process in cells of the population with kinetics that approximate first-order kinetics. We postulate that appropriate growth factors or second messenger agonists block the initiating event that starts the cell death process.", "contents": "Dissociation between early loss of actin fibres and subsequent cell death in serum-deprived quiescent Balb/c-3T3 cells. Serum withdrawal from either growing or quiescent Balb/c-3T3 murine fibroblasts causes a loss of F-actin fibres and focal adhesions within 30 min. Cells that are growing survive serum deprivation, whereas the great majority of density-arrested quiescent cells die during a period of up to 5 h from serum withdrawal. During this time an approximately constant fraction of the quiescent cell population dies per unit time. The population half-life is 60-70 min during this time. Addition of an appropriate cell growth factor or second messenger agonist at the time of serum withdrawal or within 2 h after serum withdrawal protects a similar fraction of viable cells. These findings suggest a model according to which withdrawal of serum (i.e. growth factors) initiates the death process in cells of the population with kinetics that approximate first-order kinetics. We postulate that appropriate growth factors or second messenger agonists block the initiating event that starts the cell death process."} {"id": "PMID:1283312", "title": "Differential phosphorylation of CK8 and CK18 by 12-O-tetradecanoyl-phorbol-13-acetate in primary cultures of mouse hepatocytes.", "content": "The phosphorylation of cytokeratin was investigated in primary cultures of hepatocytes. The two hepatocyte cytokeratins CK8 and CK18 (55,000 and 49,000 M(r) respectively) were phosphorylated, CK8 being more phosphorylated than CK18. Treatment of the hepatocytes with 150 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) an activator of protein kinase C induced a transient increase in the level of phosphorylation of CK8 but not CK18. This effect was maximal after 15 min of TPA treatment and was maintained for up to 3 h. After 22 h of treatment with TPA, which down-regulates protein kinase C, CK8 phosphorylation was returned to the basal level. Further addition of TPA to the 22-h treated cells did not cause an increase in CK8 phosphorylation. Indirect immunofluorescence microscopy with a monoclonal antibody to CK8 indicated that while the addition of TPA induced the formation of granular cytokeratin aggregates in some hepatocytes, in most hepatocytes no major changes in the intermediate filament network were observed. Staining for actin showed that actin microfilaments were rapidly reorganized after the treatment and a loss of stress fibres were observed. We propose that CK8 is an in vivo substrate for protein kinase C and that the specific phosphorylation of CK8 plays a role in protein kinase C signal transduction.", "contents": "Differential phosphorylation of CK8 and CK18 by 12-O-tetradecanoyl-phorbol-13-acetate in primary cultures of mouse hepatocytes. The phosphorylation of cytokeratin was investigated in primary cultures of hepatocytes. The two hepatocyte cytokeratins CK8 and CK18 (55,000 and 49,000 M(r) respectively) were phosphorylated, CK8 being more phosphorylated than CK18. Treatment of the hepatocytes with 150 nM 12-O-tetradecanoyl-phorbol-13-acetate (TPA) an activator of protein kinase C induced a transient increase in the level of phosphorylation of CK8 but not CK18. This effect was maximal after 15 min of TPA treatment and was maintained for up to 3 h. After 22 h of treatment with TPA, which down-regulates protein kinase C, CK8 phosphorylation was returned to the basal level. Further addition of TPA to the 22-h treated cells did not cause an increase in CK8 phosphorylation. Indirect immunofluorescence microscopy with a monoclonal antibody to CK8 indicated that while the addition of TPA induced the formation of granular cytokeratin aggregates in some hepatocytes, in most hepatocytes no major changes in the intermediate filament network were observed. Staining for actin showed that actin microfilaments were rapidly reorganized after the treatment and a loss of stress fibres were observed. We propose that CK8 is an in vivo substrate for protein kinase C and that the specific phosphorylation of CK8 plays a role in protein kinase C signal transduction."} {"id": "PMID:1283313", "title": "Pax-5 is expressed at the midbrain-hindbrain boundary during mouse development.", "content": "The murine paired-box-containing gene 5, Pax-5, is highly homologous to two other Pax genes, Pax-2 and Pax-8. The expression pattern of Pax-5 during mouse embryogenesis was examined by in situ RNA hybridization and compared to those of Pax-2 and Pax-8. Beginning at day 9.5 postcoitum (p.c.), Pax-5 was expressed in the developing brain, predominantly at the midbrain-hindbrain boundary, and in the neural tube. While the neural tube expression pattern overlapped completely with Pax-2 and Pax-8, the expression pattern in the brain was only partially overlapping. Unlike Pax-2 and Pax-8, Pax-5 was not expressed in the developing excretory system, thyroid, eye or ear. Our data suggest that Pax-5 has a role in the development of the central nervous system.", "contents": "Pax-5 is expressed at the midbrain-hindbrain boundary during mouse development. The murine paired-box-containing gene 5, Pax-5, is highly homologous to two other Pax genes, Pax-2 and Pax-8. The expression pattern of Pax-5 during mouse embryogenesis was examined by in situ RNA hybridization and compared to those of Pax-2 and Pax-8. Beginning at day 9.5 postcoitum (p.c.), Pax-5 was expressed in the developing brain, predominantly at the midbrain-hindbrain boundary, and in the neural tube. While the neural tube expression pattern overlapped completely with Pax-2 and Pax-8, the expression pattern in the brain was only partially overlapping. Unlike Pax-2 and Pax-8, Pax-5 was not expressed in the developing excretory system, thyroid, eye or ear. Our data suggest that Pax-5 has a role in the development of the central nervous system."} {"id": "PMID:1283314", "title": "Enhancer trap integrations in mouse embryonic stem cells give rise to staining patterns in chimaeric embryos with a high frequency and detect endogenous genes.", "content": "We have generated mouse embryonic stem cell lines that carry lacZ enhancer trap constructs integrated in their genome. Fifty-nine cell lines were analysed for lacZ expression in undifferentiated stem cells and at day 7.5, 8.5 and 12.5 of development in chimaeric embryos obtained after blastocyst injection. In 13 cell lines the lacZ reporter gene was expressed in undifferentiated stem cells ('blue', lines) as monitored by beta-galactosidase activity; 46 cell lines did not show detectable beta-galactosidase activity ('white', lines). In chimaeric embryos one-third of the analysed 59 embryonic stem cell lines gave rise to a variety of patterns. Six out of the 13 'blue' lines and 14 out of the 46 'white' lines showed spatially and temporally regulated patterns of beta-galactosidase expression and were additionally analysed on day 9.5. The majority of patterns showed staining exclusively or predominantly in structures of the developing nervous system, three patterns were observed only or predominantly in non-neuronal structures and five patterns were found exclusively in extraembryonic tissues. The analysis of DNA from cell lines that gave rise to staining patterns in chimaeric embryos showed that in 11 out of 15 cases simple integrations had occurred at a single site while in the remaining four cell lines multiple copies had integrated either at a single or at multiple sites. Flanking sequences from five reporter gene integrations have been cloned. At present, three integration sites have been analysed further and in all three cases we have identified transcribed sequences in the flanking DNA and isolated corresponding cDNA clones. The expression patterns of two of these genes were analysed by RNA in situ hybridisation. In both cases, expression of the endogenous genes was more widespread than the corresponding beta-galactosidase staining, suggesting that the reporter gene responded to only a subset of the regulatory elements of the endogenous gene. Our results demonstrate that enhancer trap integrations in embryonic stem cells can be used to efficiently identify transcriptional activation patterns during mouse embryogenesis and to isolate endogenous genes expressed in spatially and temporally regulated patterns.", "contents": "Enhancer trap integrations in mouse embryonic stem cells give rise to staining patterns in chimaeric embryos with a high frequency and detect endogenous genes. We have generated mouse embryonic stem cell lines that carry lacZ enhancer trap constructs integrated in their genome. Fifty-nine cell lines were analysed for lacZ expression in undifferentiated stem cells and at day 7.5, 8.5 and 12.5 of development in chimaeric embryos obtained after blastocyst injection. In 13 cell lines the lacZ reporter gene was expressed in undifferentiated stem cells ('blue', lines) as monitored by beta-galactosidase activity; 46 cell lines did not show detectable beta-galactosidase activity ('white', lines). In chimaeric embryos one-third of the analysed 59 embryonic stem cell lines gave rise to a variety of patterns. Six out of the 13 'blue' lines and 14 out of the 46 'white' lines showed spatially and temporally regulated patterns of beta-galactosidase expression and were additionally analysed on day 9.5. The majority of patterns showed staining exclusively or predominantly in structures of the developing nervous system, three patterns were observed only or predominantly in non-neuronal structures and five patterns were found exclusively in extraembryonic tissues. The analysis of DNA from cell lines that gave rise to staining patterns in chimaeric embryos showed that in 11 out of 15 cases simple integrations had occurred at a single site while in the remaining four cell lines multiple copies had integrated either at a single or at multiple sites. Flanking sequences from five reporter gene integrations have been cloned. At present, three integration sites have been analysed further and in all three cases we have identified transcribed sequences in the flanking DNA and isolated corresponding cDNA clones. The expression patterns of two of these genes were analysed by RNA in situ hybridisation. In both cases, expression of the endogenous genes was more widespread than the corresponding beta-galactosidase staining, suggesting that the reporter gene responded to only a subset of the regulatory elements of the endogenous gene. Our results demonstrate that enhancer trap integrations in embryonic stem cells can be used to efficiently identify transcriptional activation patterns during mouse embryogenesis and to isolate endogenous genes expressed in spatially and temporally regulated patterns."} {"id": "PMID:1283315", "title": "Cloning and characterization of the Ewing's sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints.", "content": "Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12). The cos5 locus, previously identified in the vicinity of the chromosome 22 breakpoint of this translocation, was shown by in situ hybridization on interphase nuclei to lie between VIIIF2 and LIF, two loci located on either side of the breakpoint and at a distance of less than 2,000 kb. The progressive expansion of this locus by chromosome walking led to the construction of a 300 kb contig, which finally crossed the breakpoint. The subsequent cloning of the two translocation junction fragments of a PN, followed by the molecular characterization of the translocation breakpoints of 20 ES and PN, showed that most chromosome 22 breakpoints are clustered within a small, 2 kb region. In contrast, the chromosome 11 breakpoints are scattered over a region of at least 40 kb. The translocation leads to the synthesis of chimeric transcript that links sequences from chromosomes 22 and 11. Finally, no evidence was found of any specific difference in the position of ES and PN translocation breakpoints.", "contents": "Cloning and characterization of the Ewing's sarcoma and peripheral neuroepithelioma t(11;22) translocation breakpoints. Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12). The cos5 locus, previously identified in the vicinity of the chromosome 22 breakpoint of this translocation, was shown by in situ hybridization on interphase nuclei to lie between VIIIF2 and LIF, two loci located on either side of the breakpoint and at a distance of less than 2,000 kb. The progressive expansion of this locus by chromosome walking led to the construction of a 300 kb contig, which finally crossed the breakpoint. The subsequent cloning of the two translocation junction fragments of a PN, followed by the molecular characterization of the translocation breakpoints of 20 ES and PN, showed that most chromosome 22 breakpoints are clustered within a small, 2 kb region. In contrast, the chromosome 11 breakpoints are scattered over a region of at least 40 kb. The translocation leads to the synthesis of chimeric transcript that links sequences from chromosomes 22 and 11. Finally, no evidence was found of any specific difference in the position of ES and PN translocation breakpoints."} {"id": "PMID:1283316", "title": "Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).", "content": "Most myxoid liposarcomas (MLS) are characterized cytogenetically by a t(12;16)(q13;p11). It is reasonable to assume that this translocation corresponds to the consistent rearrangement of one or two genes in 12q13 and/or 16p11, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation. We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps to 12q13 and is assumed to be involved in adipocyte differentiation, could be the 12q gene in question. Using a cDNA probe that spans the CHOP coding region, we detected one rearranged and one wild type allele in nine of nine MLS with t(12;16). Using PCR generated, site-specific probes corresponding to the non-coding exons 1 and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 2.4 and 1.6 kbp PstI fragments that contain the first two exons and introns of the gene and the upstream promoter region. In contrast to the findings in MLS, no tumor without a t(12;16) exhibited aberrant CHOP restriction digest patterns. These tumors included one highly differentiated liposarcoma with abnormal karyotype but no involvement of 12q13, seven lipomas with various cytogenetic aberrations of 12q13-15, two uterine leiomyomas with t(12;14) (q14-15;q23-24), and one hemangiopericytoma and one chondroma, both of which also had 12q13 changes.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11). Most myxoid liposarcomas (MLS) are characterized cytogenetically by a t(12;16)(q13;p11). It is reasonable to assume that this translocation corresponds to the consistent rearrangement of one or two genes in 12q13 and/or 16p11, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation. We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps to 12q13 and is assumed to be involved in adipocyte differentiation, could be the 12q gene in question. Using a cDNA probe that spans the CHOP coding region, we detected one rearranged and one wild type allele in nine of nine MLS with t(12;16). Using PCR generated, site-specific probes corresponding to the non-coding exons 1 and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 2.4 and 1.6 kbp PstI fragments that contain the first two exons and introns of the gene and the upstream promoter region. In contrast to the findings in MLS, no tumor without a t(12;16) exhibited aberrant CHOP restriction digest patterns. These tumors included one highly differentiated liposarcoma with abnormal karyotype but no involvement of 12q13, seven lipomas with various cytogenetic aberrations of 12q13-15, two uterine leiomyomas with t(12;14) (q14-15;q23-24), and one hemangiopericytoma and one chondroma, both of which also had 12q13 changes.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283317", "title": "Tumor-associated karyotypic lesions coselected with in vitro macrophage differentiation.", "content": "Several cytogenetic lesions in chromosomes 2, 5, 12, and 16 have been repeatedly coselected with in vitro macrophage differentiation in a clonal murine thymic tumor cell line. Parental-type subclones, which show an extremely immature hemopoietic phenotype, do not carry the aberrations. The frequency of the stable differentiated variants is elevated by 5-azacytidine and bromodeoxyuridine, consistent with chromosome breakage being responsible for the phenotype. The frequency is also raised by dexamethasone. Since variants are 300-3,000-fold more resistant to dexamethasone than parental clones, we interpret this to be largely due to selection. Three of the lesions, on chromosome 2, match those previously described as associated specifically with in vivo-generated murine myeloid tumors, induced by X irradiation and corticosteroid treatment. Several implications follow from these observations. (1) In vitro differentiation in clonal tumor cell lines can be used to select for tumor-associated lesions. This should allow genetic and molecular analysis of the chromosome 2 lesions and of others that may pinpoint genes critical to macrophage differentiation and transformation. (2) Myeloid and lymphoid tumors that occur in response to X irradiation may diverge from a common initiating tumor. (3) The hemopoietic lineage switch phenomenon, previously described by several authors, may be caused by similar or identical chromosome aberrations.", "contents": "Tumor-associated karyotypic lesions coselected with in vitro macrophage differentiation. Several cytogenetic lesions in chromosomes 2, 5, 12, and 16 have been repeatedly coselected with in vitro macrophage differentiation in a clonal murine thymic tumor cell line. Parental-type subclones, which show an extremely immature hemopoietic phenotype, do not carry the aberrations. The frequency of the stable differentiated variants is elevated by 5-azacytidine and bromodeoxyuridine, consistent with chromosome breakage being responsible for the phenotype. The frequency is also raised by dexamethasone. Since variants are 300-3,000-fold more resistant to dexamethasone than parental clones, we interpret this to be largely due to selection. Three of the lesions, on chromosome 2, match those previously described as associated specifically with in vivo-generated murine myeloid tumors, induced by X irradiation and corticosteroid treatment. Several implications follow from these observations. (1) In vitro differentiation in clonal tumor cell lines can be used to select for tumor-associated lesions. This should allow genetic and molecular analysis of the chromosome 2 lesions and of others that may pinpoint genes critical to macrophage differentiation and transformation. (2) Myeloid and lymphoid tumors that occur in response to X irradiation may diverge from a common initiating tumor. (3) The hemopoietic lineage switch phenomenon, previously described by several authors, may be caused by similar or identical chromosome aberrations."} {"id": "PMID:1283318", "title": "Cytogenetic studies in subgroups of rhabdomyosarcoma.", "content": "Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and accounts for 10% of all solid tumors in children. There are three different histologic forms of this tumor: embryonal (RMS-E), alveolar (RMS-A), and primitive (RMS-P). Among these, the embryonal form has responded well to chemotherapy. Identification of the correct subtype is important for both the management and treatment of this malignancy. However, the histopathologic classification of RMS is sometimes difficult and distinguishing between the embryonic and primitive forms can present a diagnostic dilemma. Chromosomal abnormalities have been observed in all subtypes. We present the cytogenetic findings in six cases of RMS or related sarcoma. All four cases with RMS-A had both numerical and structural abnormalities in the tumor and involved bone marrow specimens. Three patients had a common marker, t(2;13)(q37;q14), and one patient had a variant marker involving 13q14, t(1;13) (p36;q14), and double minutes (dmin). The single embryonal RMS patient had modal chromosome numbers in the hypertriploid range and extensive structural abnormalities; the t(2;13) was not present, but translocation of 13q to both 1q and 2p was observed, der(1)t(1;13)(q21;q14) and der(2)t(2;13)(p25;q14). The patient with primitive type RMS had a hypodiploid line with several markers, including a complex translocation involving chromosomes 5 and 13 with a breakpoint at 13q14, and t(11;12)(q24;q12), a chromosome marker heretofore found only in Ewing's sarcoma and related tumors. This patient had atypical RMS with mixed neural and myogenic elements. The significance of these chromosomal markers and their importance in the characterization of childhood tumors are discussed, along with a review of the literature.", "contents": "Cytogenetic studies in subgroups of rhabdomyosarcoma. Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma of childhood and accounts for 10% of all solid tumors in children. There are three different histologic forms of this tumor: embryonal (RMS-E), alveolar (RMS-A), and primitive (RMS-P). Among these, the embryonal form has responded well to chemotherapy. Identification of the correct subtype is important for both the management and treatment of this malignancy. However, the histopathologic classification of RMS is sometimes difficult and distinguishing between the embryonic and primitive forms can present a diagnostic dilemma. Chromosomal abnormalities have been observed in all subtypes. We present the cytogenetic findings in six cases of RMS or related sarcoma. All four cases with RMS-A had both numerical and structural abnormalities in the tumor and involved bone marrow specimens. Three patients had a common marker, t(2;13)(q37;q14), and one patient had a variant marker involving 13q14, t(1;13) (p36;q14), and double minutes (dmin). The single embryonal RMS patient had modal chromosome numbers in the hypertriploid range and extensive structural abnormalities; the t(2;13) was not present, but translocation of 13q to both 1q and 2p was observed, der(1)t(1;13)(q21;q14) and der(2)t(2;13)(p25;q14). The patient with primitive type RMS had a hypodiploid line with several markers, including a complex translocation involving chromosomes 5 and 13 with a breakpoint at 13q14, and t(11;12)(q24;q12), a chromosome marker heretofore found only in Ewing's sarcoma and related tumors. This patient had atypical RMS with mixed neural and myogenic elements. The significance of these chromosomal markers and their importance in the characterization of childhood tumors are discussed, along with a review of the literature."} {"id": "PMID:1283319", "title": "Chromosome 1 alterations in breast cancer: allelic loss on 1p and 1q is related to lymphogenic metastases and poor prognosis.", "content": "The development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome 1. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA to determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin (PEM or MUCI) gene at 1q21 was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in the PEM gene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors. DNA ploidy, S phase fraction, protooncogene amplification, histological type, or patient age. However, LOH in the PEM gene was significantly correlated with early disease recurrence (P = 0.006). LOH on 1p was found in 27% of 117 informative cases, using probes for either D1S57 or D1Z2 located at 1p33-p35 and 1p36, respectively. Somatic allelic imbalance on 1p and 1q seemed to be independent events and not the effect of loss of a whole chromosome 1. LOH on 1p was significantly correlated to the presence of lymph node metastasis, to larger tumor size, and to DNA nondiploidy, but not correlation was found to disease outcome at this limited duration of follow-up (median 29 months).", "contents": "Chromosome 1 alterations in breast cancer: allelic loss on 1p and 1q is related to lymphogenic metastases and poor prognosis. The development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome 1. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA to determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin (PEM or MUCI) gene at 1q21 was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in the PEM gene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors. DNA ploidy, S phase fraction, protooncogene amplification, histological type, or patient age. However, LOH in the PEM gene was significantly correlated with early disease recurrence (P = 0.006). LOH on 1p was found in 27% of 117 informative cases, using probes for either D1S57 or D1Z2 located at 1p33-p35 and 1p36, respectively. Somatic allelic imbalance on 1p and 1q seemed to be independent events and not the effect of loss of a whole chromosome 1. LOH on 1p was significantly correlated to the presence of lymph node metastasis, to larger tumor size, and to DNA nondiploidy, but not correlation was found to disease outcome at this limited duration of follow-up (median 29 months)."} {"id": "PMID:1283320", "title": "Molecular analysis of a new translocation, t(X;14)(q28;q11), in premalignancy and in leukaemia associated with ataxia telangiectasia.", "content": "The disease ataxia telangiectasia (A-T) is a multifaceted disorder in which patients have an increased chance of developing a T-cell leukaemia, often with abnormalities of chromosome 14, but sometimes with rare translocations, like t(X;14)(q28;q11). We describe the cloning of the breakpoint of one such novel t(X;14) from an A-T patient. The translocation breaks within the T cell receptor alpha chain gene on chromosome 14 at band q11 and in a region of the X chromosome, within about 1 Mb of the telomere of the long arm. The patient subsequently developed T-cell prolymphocytic leukaemia (T-PLL), and molecular examination showed that the tumour cells carried the same t(X;14) breakpoint as that cloned from the premalignant cells. The same breakpoint could be detected in blood samples taken as much as 5 years prior to diagnosis of T-PLL. This suggests a role for the abnormality in the tumour development in this patient but implies that other mutational events were necessary for overt disease to become manifest.", "contents": "Molecular analysis of a new translocation, t(X;14)(q28;q11), in premalignancy and in leukaemia associated with ataxia telangiectasia. The disease ataxia telangiectasia (A-T) is a multifaceted disorder in which patients have an increased chance of developing a T-cell leukaemia, often with abnormalities of chromosome 14, but sometimes with rare translocations, like t(X;14)(q28;q11). We describe the cloning of the breakpoint of one such novel t(X;14) from an A-T patient. The translocation breaks within the T cell receptor alpha chain gene on chromosome 14 at band q11 and in a region of the X chromosome, within about 1 Mb of the telomere of the long arm. The patient subsequently developed T-cell prolymphocytic leukaemia (T-PLL), and molecular examination showed that the tumour cells carried the same t(X;14) breakpoint as that cloned from the premalignant cells. The same breakpoint could be detected in blood samples taken as much as 5 years prior to diagnosis of T-PLL. This suggests a role for the abnormality in the tumour development in this patient but implies that other mutational events were necessary for overt disease to become manifest."} {"id": "PMID:1283321", "title": "Loss of heterozygosity mapping in Wilms tumor indicates the involvement of three distinct regions and a limited role for nondisjunction or mitotic recombination.", "content": "Loss of heterozygosity (LOH) for polymorphic markers is a frequently occurring event in some tumors, reflecting the role of allele loss in the development of these tumors. We have determined LOH in 38 cases of Wilms tumor for the 2 known loci on chromosome arm 11p and for a newly detected locus on chromosome arm 16q. Only 7 of the 38 tumors studied showed reduction to homozygosity of 11p13 markers. In 4 of these tumors, reduced expression of WT1 and WIT1, genes located at 11p13 and implicated in Wilms tumorigenesis, was noted. However, this was also found in 2 of 7 tumors showing LOH exclusively of 11p15 markers and in 15 of the remaining 24 tumors in which there was no LOH for 11p markers. This suggests that events not involving mitotic recombination or chromosome nondisjunction are the most common mechanisms for mutations at the 11p Wilms tumor locus. We also noted that mitotic recombination involving 11p15 loci occurred in addition to reduced expression of the 11p13 locus genes in 2 tumors, suggesting a possible interaction between these 2 loci. In addition, LOH for 16q markers was observed in 6 tumors. In one case this was coincident with reduction of WT1 and WIT1 gene expression, and in 3 other cases it occurred in addition to 11p LOH. This indicates that an additional locus on 16q is likely to be involved in Wilms tumorigenesis.", "contents": "Loss of heterozygosity mapping in Wilms tumor indicates the involvement of three distinct regions and a limited role for nondisjunction or mitotic recombination. Loss of heterozygosity (LOH) for polymorphic markers is a frequently occurring event in some tumors, reflecting the role of allele loss in the development of these tumors. We have determined LOH in 38 cases of Wilms tumor for the 2 known loci on chromosome arm 11p and for a newly detected locus on chromosome arm 16q. Only 7 of the 38 tumors studied showed reduction to homozygosity of 11p13 markers. In 4 of these tumors, reduced expression of WT1 and WIT1, genes located at 11p13 and implicated in Wilms tumorigenesis, was noted. However, this was also found in 2 of 7 tumors showing LOH exclusively of 11p15 markers and in 15 of the remaining 24 tumors in which there was no LOH for 11p markers. This suggests that events not involving mitotic recombination or chromosome nondisjunction are the most common mechanisms for mutations at the 11p Wilms tumor locus. We also noted that mitotic recombination involving 11p15 loci occurred in addition to reduced expression of the 11p13 locus genes in 2 tumors, suggesting a possible interaction between these 2 loci. In addition, LOH for 16q markers was observed in 6 tumors. In one case this was coincident with reduction of WT1 and WIT1 gene expression, and in 3 other cases it occurred in addition to 11p LOH. This indicates that an additional locus on 16q is likely to be involved in Wilms tumorigenesis."} {"id": "PMID:1283322", "title": "Characterization of a complex chromosomal rearrangement maps the locus for in vitro complementation of xeroderma pigmentosum group D to human chromosome band 19q13.", "content": "Microcell-mediated chromosome transfer (MMCT) is a powerful genetic technique that permits the transfer of a single chromosome from one mammalian cell to another. The utility of MMCT for gene mapping strategies is critically dependent on the careful characterization of the chromosomes being transferred. We have recently reported the identification of a single rearranged human chromosome, designated Tneo, which corrects the UV sensitivity and excision repair defect of cells of xeroderma pigmentosum genetic complementation group D (XP-D) in culture (Flejter WL et al., Proc Natl Acad Sci USA 89:261-265, 1992). Additionally, those studies demonstrated a role for the excision repair cross-complementing 2 (ERCC2) gene in the observed phenotypic correction. We now report the results of detailed conventional and molecular cytogenetic characterization of the complementing Tneo chromosome. This analysis revealed a complex rearrangement involving material from human chromosomes 16, 17, and 19. Characterization of deletions of Tneo which retained or lost XP-D complementing ability mapped the gene responsible for phenotypic correction to a small region of the terminal q-arm of this chromosome. This region includes the previously described human DNA repair gene cluster located in the region 19q13.2-q13.3, a result consistent with the notion that the in vitro correction of XP-D cells by the Tneo chromosome is rendered by the ERCC2 locus. The data illustrate the potential value of detailed cytogenetic characterization of a human chromosome present in a somatic cell hybrid, even when that material involves complex rearrangements.", "contents": "Characterization of a complex chromosomal rearrangement maps the locus for in vitro complementation of xeroderma pigmentosum group D to human chromosome band 19q13. Microcell-mediated chromosome transfer (MMCT) is a powerful genetic technique that permits the transfer of a single chromosome from one mammalian cell to another. The utility of MMCT for gene mapping strategies is critically dependent on the careful characterization of the chromosomes being transferred. We have recently reported the identification of a single rearranged human chromosome, designated Tneo, which corrects the UV sensitivity and excision repair defect of cells of xeroderma pigmentosum genetic complementation group D (XP-D) in culture (Flejter WL et al., Proc Natl Acad Sci USA 89:261-265, 1992). Additionally, those studies demonstrated a role for the excision repair cross-complementing 2 (ERCC2) gene in the observed phenotypic correction. We now report the results of detailed conventional and molecular cytogenetic characterization of the complementing Tneo chromosome. This analysis revealed a complex rearrangement involving material from human chromosomes 16, 17, and 19. Characterization of deletions of Tneo which retained or lost XP-D complementing ability mapped the gene responsible for phenotypic correction to a small region of the terminal q-arm of this chromosome. This region includes the previously described human DNA repair gene cluster located in the region 19q13.2-q13.3, a result consistent with the notion that the in vitro correction of XP-D cells by the Tneo chromosome is rendered by the ERCC2 locus. The data illustrate the potential value of detailed cytogenetic characterization of a human chromosome present in a somatic cell hybrid, even when that material involves complex rearrangements."} {"id": "PMID:1283323", "title": "Two diverged human homeobox genes involved in the differentiation of human hematopoietic progenitors map to chromosome 1, bands q41-42.1.", "content": "Proteins encoded by homeobox containing genes are sequence-specific DNA binding proteins implicated in the control of gene expression in both developing and adult tissues. Two recently characterized human homeobox genes, HB9 and HB24, are highly expressed in CD34-positive marrow cells but not in CD34-depleted marrow cells. Their expression is readily down-regulated during the differentiation of hematopoietic progenitors to specific cell lineages. In this study, genomic DNA fragments isolated with HB9 (3 kb) and HB24 (6 kb) cDNAs were used to map their chromosomal location by fluorescence in situ hybridization. Both HB9 and HB24 DNA probes gave specific hybridization signals on chromosome 1. The hybridization loci were identified by combining fluorescence images of the probe signals with fluorescence banding patterns generated by cohybridization in situ with an Alu probe (R-like banding) and by DAPI staining (G-like). The results demonstrate that the loci of the HB24 and HB9 genes are within bands 1q41-q42.1. A cohybridization experiment utilizing both probes with two-color fluorescence imaging could not resolve separate loci for the two genes.", "contents": "Two diverged human homeobox genes involved in the differentiation of human hematopoietic progenitors map to chromosome 1, bands q41-42.1. Proteins encoded by homeobox containing genes are sequence-specific DNA binding proteins implicated in the control of gene expression in both developing and adult tissues. Two recently characterized human homeobox genes, HB9 and HB24, are highly expressed in CD34-positive marrow cells but not in CD34-depleted marrow cells. Their expression is readily down-regulated during the differentiation of hematopoietic progenitors to specific cell lineages. In this study, genomic DNA fragments isolated with HB9 (3 kb) and HB24 (6 kb) cDNAs were used to map their chromosomal location by fluorescence in situ hybridization. Both HB9 and HB24 DNA probes gave specific hybridization signals on chromosome 1. The hybridization loci were identified by combining fluorescence images of the probe signals with fluorescence banding patterns generated by cohybridization in situ with an Alu probe (R-like banding) and by DAPI staining (G-like). The results demonstrate that the loci of the HB24 and HB9 genes are within bands 1q41-q42.1. A cohybridization experiment utilizing both probes with two-color fluorescence imaging could not resolve separate loci for the two genes."} {"id": "PMID:1283324", "title": "Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomas.", "content": "Cytogenetic and/or loss of heterozygosity studies were performed on 13 ependymomas, 11 pilocytic astrocytomas, and 18 oligodendrogliomas. Loss of chromosome 22 was the most frequent genetic abnormality among the ependymomas. We found no consistent genetic abnormality in pilocytic astrocytomas. The most common genetic abnormality in oligodendrogliomas was loss of a portion of chromosome 19. Each informative oligodendroglioma had loss of alleles mapped to the long arm (q) of chromosome 19. One oligodendroglioma had an apparent homozygous deletion of the D19S8 locus. Our results, when combined with those in the literature, indicate that chromosomes 9, 11, and 22 may harbor genes important for the pathogenesis of ependymomas and that 19q probably harbors a gene important for the pathogenesis of oligodendrogliomas.", "contents": "Cytogenetic and loss of heterozygosity studies in ependymomas, pilocytic astrocytomas, and oligodendrogliomas. Cytogenetic and/or loss of heterozygosity studies were performed on 13 ependymomas, 11 pilocytic astrocytomas, and 18 oligodendrogliomas. Loss of chromosome 22 was the most frequent genetic abnormality among the ependymomas. We found no consistent genetic abnormality in pilocytic astrocytomas. The most common genetic abnormality in oligodendrogliomas was loss of a portion of chromosome 19. Each informative oligodendroglioma had loss of alleles mapped to the long arm (q) of chromosome 19. One oligodendroglioma had an apparent homozygous deletion of the D19S8 locus. Our results, when combined with those in the literature, indicate that chromosomes 9, 11, and 22 may harbor genes important for the pathogenesis of ependymomas and that 19q probably harbors a gene important for the pathogenesis of oligodendrogliomas."} {"id": "PMID:1283325", "title": "Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo-astrocytomas.", "content": "The aims of this study were to correlate cytogenetic studies and molecular genetic loss of heterozygosity (LOH) analyses in human astrocytomas and mixed oligo-astrocytomas, and to locate putative tumor suppressor genes on chromosome 10. Paired blood and tumor samples from 53 patients were analyzed. The tumors included 45 diffuse astrocytomas (39 grade 4, 4 grade 3, and 2 grade 2), 1 astroblastoma, and 7 mixed oligo-astrocytomas (2 grade 4, 4 grade 3, and 1 grade 2). By cytogenetic analyses the most common numeric chromosome abnormalities were +7, -10, -13, -14, -17, +19, -22, and -Y. The most common structural abnormalities involved chromosome arms 1p, 1q, 5p, and 9p. By LOH and dosage analysis the most common molecular genetic abnormalities were of chromosome arms 5p, 6p, 7q, 9p, 10p, 10q, 13q, 14q, 17p, and 19p. When the results of all methods were combined, the most commonly abnormal chromosomes were, in descending frequency, 10, Y, 17, 7, 13, and 9. In 80 percent of cases the cytogenetic and molecular genetic studies were concordant. LOH studies were more sensitive in detecting loss of genetic material than cytogenetic analyses and accounted for 60% of the discordant results. When there were structural abnormalities, such as translocations or inversions, cytogenetic analysis was more sensitive in detecting an abnormality than molecular genetic studies. In addition to the 24 tumors which appeared to lose an entire copy of chromosome 10, there were 10 tumors with molecular genetic or cytogenetic evidence of loss of only a portion of chromosome 10. The genetic analyses of these tumors suggest that there are 2 regions on chromosome 10 that may contain potential tumor suppressor genes. One lies distal to locus D10S22 from 10q22 to 10qter, and the other lies proximal to locus TST1 on the 10q arm near the centromere or on the 10p arm.", "contents": "Correlation of cytogenetic analysis and loss of heterozygosity studies in human diffuse astrocytomas and mixed oligo-astrocytomas. The aims of this study were to correlate cytogenetic studies and molecular genetic loss of heterozygosity (LOH) analyses in human astrocytomas and mixed oligo-astrocytomas, and to locate putative tumor suppressor genes on chromosome 10. Paired blood and tumor samples from 53 patients were analyzed. The tumors included 45 diffuse astrocytomas (39 grade 4, 4 grade 3, and 2 grade 2), 1 astroblastoma, and 7 mixed oligo-astrocytomas (2 grade 4, 4 grade 3, and 1 grade 2). By cytogenetic analyses the most common numeric chromosome abnormalities were +7, -10, -13, -14, -17, +19, -22, and -Y. The most common structural abnormalities involved chromosome arms 1p, 1q, 5p, and 9p. By LOH and dosage analysis the most common molecular genetic abnormalities were of chromosome arms 5p, 6p, 7q, 9p, 10p, 10q, 13q, 14q, 17p, and 19p. When the results of all methods were combined, the most commonly abnormal chromosomes were, in descending frequency, 10, Y, 17, 7, 13, and 9. In 80 percent of cases the cytogenetic and molecular genetic studies were concordant. LOH studies were more sensitive in detecting loss of genetic material than cytogenetic analyses and accounted for 60% of the discordant results. When there were structural abnormalities, such as translocations or inversions, cytogenetic analysis was more sensitive in detecting an abnormality than molecular genetic studies. In addition to the 24 tumors which appeared to lose an entire copy of chromosome 10, there were 10 tumors with molecular genetic or cytogenetic evidence of loss of only a portion of chromosome 10. The genetic analyses of these tumors suggest that there are 2 regions on chromosome 10 that may contain potential tumor suppressor genes. One lies distal to locus D10S22 from 10q22 to 10qter, and the other lies proximal to locus TST1 on the 10q arm near the centromere or on the 10p arm."} {"id": "PMID:1283326", "title": "Detection of recurrent chromosome abnormalities in Ewing's sarcoma and peripheral neuroectodermal tumor cells using bivariate flow karyotyping.", "content": "Bivariate flow karyotyping can be used for the detection of recurrent chromosome abnormalities in tumor cells. For this purpose 2 cell lines originally derived from Ewing's sarcomas and 4 cell lines from peripheral neuroectodermal tumors were used. The characteristic t(11;22) was known to be present in 5 cell lines. The remaining cell line was known to have a variant t(2;11;22;21) translocation. Metaphase chromosomes were stained with the fluorescent dyes Hoechst 33258 and Chromomycin A3 and analyzed subsequently using bivariate flow cytometry. The resulting bivariate flow karyotypes of the tumor cells were normalized by a standardized procedure using a computerized method and compared with a reference flow karyotype of normal chromosomes. In 5 cell lines two recurring abnormal chromosome peaks were identified at positions expected for the der(11) and der(22) chromosomes characteristic for the reciprocal t(11;22)(q24;q12). In the remaining cell line with the variant t(2;11;22;21), only the peak representing the der(22) was identifiable. It is concluded that bivariate flow karyotyping can be used for the semiautomated detection of recurrent translocations and the assessment of their variability among different tumors.", "contents": "Detection of recurrent chromosome abnormalities in Ewing's sarcoma and peripheral neuroectodermal tumor cells using bivariate flow karyotyping. Bivariate flow karyotyping can be used for the detection of recurrent chromosome abnormalities in tumor cells. For this purpose 2 cell lines originally derived from Ewing's sarcomas and 4 cell lines from peripheral neuroectodermal tumors were used. The characteristic t(11;22) was known to be present in 5 cell lines. The remaining cell line was known to have a variant t(2;11;22;21) translocation. Metaphase chromosomes were stained with the fluorescent dyes Hoechst 33258 and Chromomycin A3 and analyzed subsequently using bivariate flow cytometry. The resulting bivariate flow karyotypes of the tumor cells were normalized by a standardized procedure using a computerized method and compared with a reference flow karyotype of normal chromosomes. In 5 cell lines two recurring abnormal chromosome peaks were identified at positions expected for the der(11) and der(22) chromosomes characteristic for the reciprocal t(11;22)(q24;q12). In the remaining cell line with the variant t(2;11;22;21), only the peak representing the der(22) was identifiable. It is concluded that bivariate flow karyotyping can be used for the semiautomated detection of recurrent translocations and the assessment of their variability among different tumors."} {"id": "PMID:1283327", "title": "Sublocalization of the chromosome 5 breakpoint of the 3;5 translocation in myelodysplastic syndromes and acute myeloid leukemia.", "content": "A t(3;5)(q25.1;q34) reciprocal translocation identifies a subset of cases of myelodysplastic syndrome or acute myeloid leukemia (AML) that are characterized by increased numbers of megakaryocytes and severe trilineage dysplasia. As a first step in characterizing the t(3;5) breakpoints, we asked whether the translocation involves the CSFIR/PDGFRB locus at 5q33-q35. Pulsed-field gel electrophoretic analysis of a region extending 580 kb 5' to the PDGFRB gene and 120 kb 3' to the CSFIR gene did not reveal aberrant restriction fragments in leukemic cell DNA, confirming that the breakpoint does not occur in the vicinity of these genes. To sublocalize the breakpoint, we performed Southern blot hybridizations using DNA from human x hamster somatic cell hybrids containing the normal 3, the normal 5, the derivative 3, or the derivative 5 human chromosome. Using a series of polymorphic DNA probes from the long arm of chromosome 5, which have been linked by genetic recombination, we bracketed the breakpoint to within a region that spans approximately 13 centimorgans (sex average) and is flanked by the q34-qter markers cKK5.19 and L1200 (D5S62). This analysis places the chromosome 5 breakpoint of the t(3;5) considerably telomeric to the CSFIR/PDGFRB locus, confirming our studies with pulsed-field electrophoresis. Future efforts to identify the genes affected by the t(3;5) should focus on the 5q segment described in this study.", "contents": "Sublocalization of the chromosome 5 breakpoint of the 3;5 translocation in myelodysplastic syndromes and acute myeloid leukemia. A t(3;5)(q25.1;q34) reciprocal translocation identifies a subset of cases of myelodysplastic syndrome or acute myeloid leukemia (AML) that are characterized by increased numbers of megakaryocytes and severe trilineage dysplasia. As a first step in characterizing the t(3;5) breakpoints, we asked whether the translocation involves the CSFIR/PDGFRB locus at 5q33-q35. Pulsed-field gel electrophoretic analysis of a region extending 580 kb 5' to the PDGFRB gene and 120 kb 3' to the CSFIR gene did not reveal aberrant restriction fragments in leukemic cell DNA, confirming that the breakpoint does not occur in the vicinity of these genes. To sublocalize the breakpoint, we performed Southern blot hybridizations using DNA from human x hamster somatic cell hybrids containing the normal 3, the normal 5, the derivative 3, or the derivative 5 human chromosome. Using a series of polymorphic DNA probes from the long arm of chromosome 5, which have been linked by genetic recombination, we bracketed the breakpoint to within a region that spans approximately 13 centimorgans (sex average) and is flanked by the q34-qter markers cKK5.19 and L1200 (D5S62). This analysis places the chromosome 5 breakpoint of the t(3;5) considerably telomeric to the CSFIR/PDGFRB locus, confirming our studies with pulsed-field electrophoresis. Future efforts to identify the genes affected by the t(3;5) should focus on the 5q segment described in this study."} {"id": "PMID:1283328", "title": "Recurring chromosome abnormalities in Hodgkin's disease.", "content": "Cytogenetic analysis was performed on lymph nodes or other tumor masses from 33 patients with Hodgkin's disease. Metaphase cells were obtained in 25 of the 33 cases. Analyzable abnormal clones were found in nine cases. Characteristic abnormalities included polyploidy and complex structural rearrangements nonrandomly involving certain chromosomal regions. Chromosomes most commonly gained were 2, 9, 11, 19, and 20, and those most often lost were 10, 13, 15, 16, 21, and Y. Translocation breakpoints clustered in bands 1p11-1p13, 1p36, 4q35, 14q11, and 15p11. In five patients, breakpoints were in bands to which T-cell receptor genes have been mapped. No specific, recurring translocation was identified. There was, however, recurring loss of chromosomal material from 1q, 4q, 6q, and 17p. Loss or deletions of chromosomes 4 and 6 were found in five and six patients, respectively. Deletions overlapped; the smallest overlapping segments included bands 4q25-4q27 and 6q21-6q23. The data suggest that loss of specific chromosomal regions may be important in the pathogenesis of Hodgkin's disease. With respect to tumor specificity, deletions of 4q are of particular interest because these have not been previously reported to occur nonrandomly in other human malignancies.", "contents": "Recurring chromosome abnormalities in Hodgkin's disease. Cytogenetic analysis was performed on lymph nodes or other tumor masses from 33 patients with Hodgkin's disease. Metaphase cells were obtained in 25 of the 33 cases. Analyzable abnormal clones were found in nine cases. Characteristic abnormalities included polyploidy and complex structural rearrangements nonrandomly involving certain chromosomal regions. Chromosomes most commonly gained were 2, 9, 11, 19, and 20, and those most often lost were 10, 13, 15, 16, 21, and Y. Translocation breakpoints clustered in bands 1p11-1p13, 1p36, 4q35, 14q11, and 15p11. In five patients, breakpoints were in bands to which T-cell receptor genes have been mapped. No specific, recurring translocation was identified. There was, however, recurring loss of chromosomal material from 1q, 4q, 6q, and 17p. Loss or deletions of chromosomes 4 and 6 were found in five and six patients, respectively. Deletions overlapped; the smallest overlapping segments included bands 4q25-4q27 and 6q21-6q23. The data suggest that loss of specific chromosomal regions may be important in the pathogenesis of Hodgkin's disease. With respect to tumor specificity, deletions of 4q are of particular interest because these have not been previously reported to occur nonrandomly in other human malignancies."} {"id": "PMID:1283329", "title": "Loss of heterozygosity on the long arm of chromosome 22 in pheochromocytoma.", "content": "To identify the putative common deleted region on the long arm of chromosome 22 in pheochromocytoma, restriction fragment length polymorphism analysis was performed in 17 pheochromocytomas. All cases were heterozygous for at least one of the eight marker loci on 22q. Loss of heterozygosity (LOH) was observed in nine pheochromocytomas, of which eight were hereditary and one nonhereditary. Three pheochromocytomas had interstitial deletions that enabled us to localize the commonly deleted region as distal to D22S10 and proximal to D22S22. Hereditary pheochromocytoma frequently occurs in association with medullary thyroid carcinoma (MTC). Therefore, we also studied allelic loss on 22q in 23 hereditary MTCs. Only one of the MTCs showed LOH on 22q. Recent studies have mapped tumor suppressor loci associated with meningioma and neurofibromatosis type 2 (NF2) to 22q. The commonly deleted region in pheochromocytoma found by us encompasses the regions to which tumor suppressor genes associated with NF2 and meningioma have been mapped. The exact role of the pheochromocytoma tumor suppressor gene on 22q and its relationship to the suppressor genes involved in NF2 and meningioma remain unknown.", "contents": "Loss of heterozygosity on the long arm of chromosome 22 in pheochromocytoma. To identify the putative common deleted region on the long arm of chromosome 22 in pheochromocytoma, restriction fragment length polymorphism analysis was performed in 17 pheochromocytomas. All cases were heterozygous for at least one of the eight marker loci on 22q. Loss of heterozygosity (LOH) was observed in nine pheochromocytomas, of which eight were hereditary and one nonhereditary. Three pheochromocytomas had interstitial deletions that enabled us to localize the commonly deleted region as distal to D22S10 and proximal to D22S22. Hereditary pheochromocytoma frequently occurs in association with medullary thyroid carcinoma (MTC). Therefore, we also studied allelic loss on 22q in 23 hereditary MTCs. Only one of the MTCs showed LOH on 22q. Recent studies have mapped tumor suppressor loci associated with meningioma and neurofibromatosis type 2 (NF2) to 22q. The commonly deleted region in pheochromocytoma found by us encompasses the regions to which tumor suppressor genes associated with NF2 and meningioma have been mapped. The exact role of the pheochromocytoma tumor suppressor gene on 22q and its relationship to the suppressor genes involved in NF2 and meningioma remain unknown."} {"id": "PMID:1283330", "title": "Human RAG2, like RAG1, is on chromosome 11 band p13 and therefore not linked to ataxia telangiectasia complementation groups.", "content": "Ataxia telangiectasia (A-T) is an inherited, recessive, cancer-prone disease with associated immunodeficiency and chromosome abnormalities involving TCR loci. The latter phenomena implicate errors of the enzyme(s) responsible for assembly of antigen receptor genes (recombinase) in disease pathogenesis. Here we report the location of a human recombination activating gene (RAG2), in addition to RAG1, on chromosome 11, band p13, thereby formally demonstrating linkage of these genes in humans and showing that they are not linked to the known locus responsible for the A-T syndrome.", "contents": "Human RAG2, like RAG1, is on chromosome 11 band p13 and therefore not linked to ataxia telangiectasia complementation groups. Ataxia telangiectasia (A-T) is an inherited, recessive, cancer-prone disease with associated immunodeficiency and chromosome abnormalities involving TCR loci. The latter phenomena implicate errors of the enzyme(s) responsible for assembly of antigen receptor genes (recombinase) in disease pathogenesis. Here we report the location of a human recombination activating gene (RAG2), in addition to RAG1, on chromosome 11, band p13, thereby formally demonstrating linkage of these genes in humans and showing that they are not linked to the known locus responsible for the A-T syndrome."} {"id": "PMID:1283331", "title": "Clonal cytogenetic abnormalities and telomeric associations in a fibroxanthoma of the stomach.", "content": "A cytogenetic study of a fibroxanthoma (fibrous histiocytoma) of the stomach revealed a clonal structural abnormality involving chromosome 12 and frequent telomeric associations between the short arm of chromosome 12 and different chromosomes. A marker chromosome possibly derived from chromosome 11 was also present. This is the second reported case of gastric fibroxanthoma and the first studied cytogenetically.", "contents": "Clonal cytogenetic abnormalities and telomeric associations in a fibroxanthoma of the stomach. A cytogenetic study of a fibroxanthoma (fibrous histiocytoma) of the stomach revealed a clonal structural abnormality involving chromosome 12 and frequent telomeric associations between the short arm of chromosome 12 and different chromosomes. A marker chromosome possibly derived from chromosome 11 was also present. This is the second reported case of gastric fibroxanthoma and the first studied cytogenetically."} {"id": "PMID:1283332", "title": "Identification and quantification of a naturally presented peptide as recognized by cytotoxic T lymphocytes specific for an immunogenic tumor variant.", "content": "The target antigen recognized by H-2Kd-restricted cytotoxic T lymphocytes (CTLs) specific for a mutagen-induced antigen on DBA/2-derived tumor P815 was identified as the product of a normal cellular gene encompassing a point mutation. Using synthetic peptides, the epitope recognized by these CTLs was narrowed down to be contained within the undecamer KYQAVTTTLEE, incorporating the point mutation. The allele-specific peptide motif for H-2Kd molecules allowed us to predict the peptide naturally presented by the tumor cells to be the nonamer KYQAVTTTL. Isolation of the natural tum(-)-specific peptide from P198.3 tumor cells and biochemical comparison with the synthetic nonamer confirmed the prediction. This natural nonapeptide is represented by approximately 100 copies per tumor cell.", "contents": "Identification and quantification of a naturally presented peptide as recognized by cytotoxic T lymphocytes specific for an immunogenic tumor variant. The target antigen recognized by H-2Kd-restricted cytotoxic T lymphocytes (CTLs) specific for a mutagen-induced antigen on DBA/2-derived tumor P815 was identified as the product of a normal cellular gene encompassing a point mutation. Using synthetic peptides, the epitope recognized by these CTLs was narrowed down to be contained within the undecamer KYQAVTTTLEE, incorporating the point mutation. The allele-specific peptide motif for H-2Kd molecules allowed us to predict the peptide naturally presented by the tumor cells to be the nonamer KYQAVTTTL. Isolation of the natural tum(-)-specific peptide from P198.3 tumor cells and biochemical comparison with the synthetic nonamer confirmed the prediction. This natural nonapeptide is represented by approximately 100 copies per tumor cell."} {"id": "PMID:1283333", "title": "Novel cell junctions induced by activating Thy-1-specific antibodies.", "content": "KT16, like other anti-Thy-1 antibodies, induces T cell aggregation. Protein A-gold labelling shows the antibody to be concentrated along areas of intercellular contacts. Electron micrographs of KT16 treated T cells reveal a consistent type of junction between the cells. We demonstrate that this type of cell junction is Thy-1 specific, is predominantly the property of antibodies directed against a particular epitope, and is distinct from cellular aggregation caused by concanavalin A or anti-CD3 antibodies. The degree of adhesiveness induced by different anti-Thy-1 antibodies is related to their mitogenic capacity.", "contents": "Novel cell junctions induced by activating Thy-1-specific antibodies. KT16, like other anti-Thy-1 antibodies, induces T cell aggregation. Protein A-gold labelling shows the antibody to be concentrated along areas of intercellular contacts. Electron micrographs of KT16 treated T cells reveal a consistent type of junction between the cells. We demonstrate that this type of cell junction is Thy-1 specific, is predominantly the property of antibodies directed against a particular epitope, and is distinct from cellular aggregation caused by concanavalin A or anti-CD3 antibodies. The degree of adhesiveness induced by different anti-Thy-1 antibodies is related to their mitogenic capacity."} {"id": "PMID:1283334", "title": "On the origin of natural IgM in immunoglobulin transgenic mice.", "content": "Surface transgenic IgM was expressed by > 95% of small resting splenic B cells but only by 50% of CD5+ and CD5- peritoneal B cells from the mu-transgenic mouse line M54. Transgenic male M54 were crossed with female CBA/N mice carrying the Xid defect. Offspring F1 animals carrying the transgene were analysed for the presence of transgenic and endogenous IgM expressed both in the serum as well as on the surface of splenic and peritoneal B cells. We found that the levels of serum IgM coded for by the transgene were similar in both F1 male, which lack CD5 B cells, and female transgenic mice, which have CD5 B cells. Thus, the Xid defect does not influence the expression of the transgene at the level of naturally activated plasma cells, a finding substantiated by the fact that both male and female naturally activated splenic plasma cells express the transgene at the same frequency. F1 hybrid mice, like transgenic C57BI/6 M54 mice, have naturally activated splenic plasma cells that overexpress endogenous IgM coded for by the VH gene family Q52. The data indicate that normal serum IgM is not derived from CD5+ B cells and that the serum IgM coded for by the mu-transgene from M54 is produced at normal levels even in the male F1 mouse which lacks CD5+ B cells.", "contents": "On the origin of natural IgM in immunoglobulin transgenic mice. Surface transgenic IgM was expressed by > 95% of small resting splenic B cells but only by 50% of CD5+ and CD5- peritoneal B cells from the mu-transgenic mouse line M54. Transgenic male M54 were crossed with female CBA/N mice carrying the Xid defect. Offspring F1 animals carrying the transgene were analysed for the presence of transgenic and endogenous IgM expressed both in the serum as well as on the surface of splenic and peritoneal B cells. We found that the levels of serum IgM coded for by the transgene were similar in both F1 male, which lack CD5 B cells, and female transgenic mice, which have CD5 B cells. Thus, the Xid defect does not influence the expression of the transgene at the level of naturally activated plasma cells, a finding substantiated by the fact that both male and female naturally activated splenic plasma cells express the transgene at the same frequency. F1 hybrid mice, like transgenic C57BI/6 M54 mice, have naturally activated splenic plasma cells that overexpress endogenous IgM coded for by the VH gene family Q52. The data indicate that normal serum IgM is not derived from CD5+ B cells and that the serum IgM coded for by the mu-transgene from M54 is produced at normal levels even in the male F1 mouse which lacks CD5+ B cells."} {"id": "PMID:1283335", "title": "Processing and presentation of insulin. III. Insulin degrading enzyme: a neutral metalloendoproteinase that is non-homologous to classical endoproteinases mediates the processing of insulin epitopes for helper T cells.", "content": "Presentation of a protein antigen to T cells generally requires that the antigen be enzymatically processed into an immunogenic peptide(s). The identification of a protease(s) and its mechanism of action in the proteolysis of such an antigen is therefore a primary goal in the study of antigen processing. We show here that insulin degrading enzyme (IDE), a neutral thiol metalloendoproteinase that is structurally non-homologous to the classical metallo, thiol, acid, or serine proteinases, is relatively specific in its proteolytic activity for insulin and digests human insulin (H(I)) into peptides that are presented by murine TA3 B cell antigen presenting cells (APCs) to HI/I-Ad-reactive T cells. These peptides are, however, not presented by fixed TA3 APCs. Anti-IDE mAbs, after their internalization by TA3 cells, significantly inhibit the presentation of H(I) by these APCs. Immunoblotting experiments demonstrate that this inhibition is mediated by the reactivity of these mAbs with a 110 kDa protein, the known M(r) of IDE. These data show that IDE is an endoproteinase that is involved in the processing of insulin and that this IDE-mediated proteolysis is necessary but not sufficient for the recognition of insulin by T cells. Furthermore, we demonstrate that reduction of the disulfide bonds of a pre-processed A-loop containing heterodimeric insulin peptide is required to further process insulin into a T cell epitope.", "contents": "Processing and presentation of insulin. III. Insulin degrading enzyme: a neutral metalloendoproteinase that is non-homologous to classical endoproteinases mediates the processing of insulin epitopes for helper T cells. Presentation of a protein antigen to T cells generally requires that the antigen be enzymatically processed into an immunogenic peptide(s). The identification of a protease(s) and its mechanism of action in the proteolysis of such an antigen is therefore a primary goal in the study of antigen processing. We show here that insulin degrading enzyme (IDE), a neutral thiol metalloendoproteinase that is structurally non-homologous to the classical metallo, thiol, acid, or serine proteinases, is relatively specific in its proteolytic activity for insulin and digests human insulin (H(I)) into peptides that are presented by murine TA3 B cell antigen presenting cells (APCs) to HI/I-Ad-reactive T cells. These peptides are, however, not presented by fixed TA3 APCs. Anti-IDE mAbs, after their internalization by TA3 cells, significantly inhibit the presentation of H(I) by these APCs. Immunoblotting experiments demonstrate that this inhibition is mediated by the reactivity of these mAbs with a 110 kDa protein, the known M(r) of IDE. These data show that IDE is an endoproteinase that is involved in the processing of insulin and that this IDE-mediated proteolysis is necessary but not sufficient for the recognition of insulin by T cells. Furthermore, we demonstrate that reduction of the disulfide bonds of a pre-processed A-loop containing heterodimeric insulin peptide is required to further process insulin into a T cell epitope."} {"id": "PMID:1283336", "title": "A report of children with spinal dysraphism managed conservatively.", "content": "This investigation is a retrospective study of 12 patients with spinal dysraphism. There were 5 males and 7 females in the cohort. Their ages ranged from 4 to 13 years at the time of their last assessment. Initial presentation included one or more of the following--a blemish on the back in the midline (lump, hairy patch, sinus and/or angioma), abnormal neurological signs and symptoms in one or both legs, and in one case dribbling of urine. Investigations performed included plain X-rays of the spine, CT scans alone or in combination with a myelogram and MR scans. Findings included thickened filum terminale, low lying cord, lipoma, syringomyelia, diastematomyelia, spina bifida occulta and sacral agenesis. The children were followed up for between 2 and 10 years. During the period of observation, none developed new symptoms or signs, and there was no progression of existing neurological deficits. This preliminary report suggests that there is no justification for prophylactic surgery in this group of patients.", "contents": "A report of children with spinal dysraphism managed conservatively. This investigation is a retrospective study of 12 patients with spinal dysraphism. There were 5 males and 7 females in the cohort. Their ages ranged from 4 to 13 years at the time of their last assessment. Initial presentation included one or more of the following--a blemish on the back in the midline (lump, hairy patch, sinus and/or angioma), abnormal neurological signs and symptoms in one or both legs, and in one case dribbling of urine. Investigations performed included plain X-rays of the spine, CT scans alone or in combination with a myelogram and MR scans. Findings included thickened filum terminale, low lying cord, lipoma, syringomyelia, diastematomyelia, spina bifida occulta and sacral agenesis. The children were followed up for between 2 and 10 years. During the period of observation, none developed new symptoms or signs, and there was no progression of existing neurological deficits. This preliminary report suggests that there is no justification for prophylactic surgery in this group of patients."} {"id": "PMID:1283337", "title": "[The effect of calcium antagonists on cholesterol metabolism in human aortal intima cells and macrophage lines].", "content": "Effects of two Ca-antagonists, verapamil and nifedipine, on the total cellular cholesterol content and accumulation, as well as on the synthesis and hydrolysis of cholesteryl esters in human aortic intimal smooth muscle cells and P388D1 cell line have been studied. Verapamil and nifedipine used at 10(-6) M and higher concentrations decreased the total cellular cholesterol content (by 25-40%) in intimal cells isolated from atherosclerotic lesions without any effect on the cholesterol content in normal intimal cells or P388D1 cells. At 2 x 10(-5) M verapamil and nifedipine prevented the accumulation of cholesterol induced by atherogenic blood serum or atherogenic low density lipoproteins in both types of cells. At 10(-5) M and higher concentrations verapamil and nifedipine inhibited (2-3-fold) cholesteryl ester synthesis in intimal cells and, used at 10(-6) M and higher doses, in P388D1 cells as well. Verapamil and nifedipine (2 x 10(-5) M) enhanced the hydrolysis of cholesteryl esters in both types of cells. The Ca-channel agonist Bay K8644 had no effect on cholesteryl ester synthesis, nor did it suppress its inhibition by Ca-antagonist. The beta-receptor blocker propranolol induced the accumulation of cholesterol in intimal cells and inhibited the synthesis and hydrolysis of cholesterol esters in these cells. The data obtained suggest that the antiatherosclerotic action of Ca-blockers is determined by their ability to reduce the cellular cholesterol content which is suggested to be the result of enhanced hydrolysis of cellular cholesteryl esters.", "contents": "[The effect of calcium antagonists on cholesterol metabolism in human aortal intima cells and macrophage lines]. Effects of two Ca-antagonists, verapamil and nifedipine, on the total cellular cholesterol content and accumulation, as well as on the synthesis and hydrolysis of cholesteryl esters in human aortic intimal smooth muscle cells and P388D1 cell line have been studied. Verapamil and nifedipine used at 10(-6) M and higher concentrations decreased the total cellular cholesterol content (by 25-40%) in intimal cells isolated from atherosclerotic lesions without any effect on the cholesterol content in normal intimal cells or P388D1 cells. At 2 x 10(-5) M verapamil and nifedipine prevented the accumulation of cholesterol induced by atherogenic blood serum or atherogenic low density lipoproteins in both types of cells. At 10(-5) M and higher concentrations verapamil and nifedipine inhibited (2-3-fold) cholesteryl ester synthesis in intimal cells and, used at 10(-6) M and higher doses, in P388D1 cells as well. Verapamil and nifedipine (2 x 10(-5) M) enhanced the hydrolysis of cholesteryl esters in both types of cells. The Ca-channel agonist Bay K8644 had no effect on cholesteryl ester synthesis, nor did it suppress its inhibition by Ca-antagonist. The beta-receptor blocker propranolol induced the accumulation of cholesterol in intimal cells and inhibited the synthesis and hydrolysis of cholesterol esters in these cells. The data obtained suggest that the antiatherosclerotic action of Ca-blockers is determined by their ability to reduce the cellular cholesterol content which is suggested to be the result of enhanced hydrolysis of cellular cholesteryl esters."} {"id": "PMID:1283338", "title": "[Energizing plasmalemma of yeasts is necessary for activation of its H+-ATPase by glucose].", "content": "ATPase of yeast plasmalemma is known to be activated during incubation of cells or protoplasts with glucose. It has been shown that the level of ATPase activation is sharply decreased after pretreatment of cells or protoplasts with mercaptoethanol, dinitrophenol, gramicidin D, nigericin, or monensin. It is suggested that deenergization of yeast plasmalemma by monensin, nigericin, and mercaptoethanol as uncoupler plays a crucial role in the prevention of in vivo activation of plasma membrane ATPase by glucose. It is concluded that energization of yeast plasmalemma is necessary for activation of ATPase by glucose.", "contents": "[Energizing plasmalemma of yeasts is necessary for activation of its H+-ATPase by glucose]. ATPase of yeast plasmalemma is known to be activated during incubation of cells or protoplasts with glucose. It has been shown that the level of ATPase activation is sharply decreased after pretreatment of cells or protoplasts with mercaptoethanol, dinitrophenol, gramicidin D, nigericin, or monensin. It is suggested that deenergization of yeast plasmalemma by monensin, nigericin, and mercaptoethanol as uncoupler plays a crucial role in the prevention of in vivo activation of plasma membrane ATPase by glucose. It is concluded that energization of yeast plasmalemma is necessary for activation of ATPase by glucose."} {"id": "PMID:1283339", "title": "[Phosphatidylinositides as biochemical modulators of the process of receptor domain formation].", "content": "A detailed description of the dynamic aspect of the previously proposed concept concerning the domain organization of receptor molecules in biological membranes is presented. Within the framework of this model, receptor molecules are considered as structural elements of the cyclic process of receptor domain (RD) formation and decay. It is assumed that receptor molecules may form a molecular basis of various physiological cyclic processes. Different pathways of biochemical control over RD formation and their putative functional roles in various receptor systems are discussed. It is suggested that phosphatidylinositol metabolism in the cell may be coupled to biochemical control over RD formation. Two probable pathways of such control, one chemical (ligand-mediated) and one autonomous, are proposed. The molecular origin of carcinogenesis is postulated.", "contents": "[Phosphatidylinositides as biochemical modulators of the process of receptor domain formation]. A detailed description of the dynamic aspect of the previously proposed concept concerning the domain organization of receptor molecules in biological membranes is presented. Within the framework of this model, receptor molecules are considered as structural elements of the cyclic process of receptor domain (RD) formation and decay. It is assumed that receptor molecules may form a molecular basis of various physiological cyclic processes. Different pathways of biochemical control over RD formation and their putative functional roles in various receptor systems are discussed. It is suggested that phosphatidylinositol metabolism in the cell may be coupled to biochemical control over RD formation. Two probable pathways of such control, one chemical (ligand-mediated) and one autonomous, are proposed. The molecular origin of carcinogenesis is postulated."} {"id": "PMID:1283340", "title": "Modified tetrachrome method for osteoid and defectively mineralized bone in paraffin sections.", "content": "A new modification of the tetrachrome method for bone osteoid in paraffin sections has been designed. The modified tetrachrome method suitable for routine use in any histology laboratory retains the simplicity of the original method and gives good results on the freshly fixed, decalcified, paraffin embedded material. Osteoid tissue is stained deep blue and normally mineralized bone is stained red. Defectively mineralized bone stains pale blue or pink and the cellular population is clearly identifiable. The ability to distinguish the osteoid tissue from mineralized bone and connective tissue and cartilage makes diagnosis of osteomalacia or osteoid producing tumors or assessment of ossification process straightforward, without the need for undecalcified sections. By displaying simultaneously irregularities in the mineralized matrix and morphology of bone cells, the method also permits the diagnosis of conditions recently described in patients with osteoporotic fractures, such as osteocytic degeneration and bone tissue defects.", "contents": "Modified tetrachrome method for osteoid and defectively mineralized bone in paraffin sections. A new modification of the tetrachrome method for bone osteoid in paraffin sections has been designed. The modified tetrachrome method suitable for routine use in any histology laboratory retains the simplicity of the original method and gives good results on the freshly fixed, decalcified, paraffin embedded material. Osteoid tissue is stained deep blue and normally mineralized bone is stained red. Defectively mineralized bone stains pale blue or pink and the cellular population is clearly identifiable. The ability to distinguish the osteoid tissue from mineralized bone and connective tissue and cartilage makes diagnosis of osteomalacia or osteoid producing tumors or assessment of ossification process straightforward, without the need for undecalcified sections. By displaying simultaneously irregularities in the mineralized matrix and morphology of bone cells, the method also permits the diagnosis of conditions recently described in patients with osteoporotic fractures, such as osteocytic degeneration and bone tissue defects."} {"id": "PMID:1283341", "title": "Improved detection of hepatitis C virus RNA by reverse transcription and polymerase chain reaction.", "content": "The polymerase chain reaction with prior reverse transcription of RNA into cDNA was applied to hepatitis C virus RNA detection in human serum samples of different origin. In order to eliminate false negative results, the following steps were optimized: RNA extraction, reverse transcription, and oligonucleotide primer selection. We compared different RNA extraction methods using guanidinium salt/detergent and proteinase K digestion/phenol extraction, and tested virus particle enrichment with polyethylene glycol precipitation and ultracentrifugation. RNA extraction with guanidinium salt/detergent was the most efficient method. Ultracentrifugation of single samples did not improve hepatitis C virus RNA detection. Polyethylene glycol precipitation performed poorly. Recombinant thermostable reverse transcriptase produced cDNA from fewer samples than did Moloney murine leukaemia virus reverse transcriptase. Nested oligonucleotide primers from the 5'-terminal non-coding region of the hepatitis C virus genome amplified cDNA from more samples than did primers from the coding regions. Thirty six anti-hepatitis C virus antibody positive samples were tested; nested primers (nucleotides 6 to 327 and 15 to 288) yielded 21 amplificates, whereas primers from the coding region produced 16 amplificates (nucleotides 4684-5276) and 5 amplificates (nucleotides 5166-5270), respectively. The most efficient combination of steps was RNA extraction with guanidinium salt solution, reverse transcription with Moloney murine leukaemia virus reverse transcriptase and nested polymerase chain reaction primed with primers from the 5'-terminal non-coding region of the hepatitis C virus genome. Other combinations produced more false negative results. Three different groups of anti-hepatitis C virus antibody positive individuals had markedly different viraemia patterns: Hepatitis C virus RNA was detected in the sera of only 10% of anti-hepatitis C virus antibody positive blood donors, but in 90% of anti-hepatitis C virus antibody positive patients with clinically manifest hepatitis C, and 90% of anti-hepatitis C virus antibody positive haemophiliacs who had received plasma products in the past which had not been virus-inactivated. No hepatitis C virus RNA could be detected in the sera of 450 anti-hepatitis C virus antibody negative blood donors with elevated serum alanine aminotransferase catalytic concentrations.", "contents": "Improved detection of hepatitis C virus RNA by reverse transcription and polymerase chain reaction. The polymerase chain reaction with prior reverse transcription of RNA into cDNA was applied to hepatitis C virus RNA detection in human serum samples of different origin. In order to eliminate false negative results, the following steps were optimized: RNA extraction, reverse transcription, and oligonucleotide primer selection. We compared different RNA extraction methods using guanidinium salt/detergent and proteinase K digestion/phenol extraction, and tested virus particle enrichment with polyethylene glycol precipitation and ultracentrifugation. RNA extraction with guanidinium salt/detergent was the most efficient method. Ultracentrifugation of single samples did not improve hepatitis C virus RNA detection. Polyethylene glycol precipitation performed poorly. Recombinant thermostable reverse transcriptase produced cDNA from fewer samples than did Moloney murine leukaemia virus reverse transcriptase. Nested oligonucleotide primers from the 5'-terminal non-coding region of the hepatitis C virus genome amplified cDNA from more samples than did primers from the coding regions. Thirty six anti-hepatitis C virus antibody positive samples were tested; nested primers (nucleotides 6 to 327 and 15 to 288) yielded 21 amplificates, whereas primers from the coding region produced 16 amplificates (nucleotides 4684-5276) and 5 amplificates (nucleotides 5166-5270), respectively. The most efficient combination of steps was RNA extraction with guanidinium salt solution, reverse transcription with Moloney murine leukaemia virus reverse transcriptase and nested polymerase chain reaction primed with primers from the 5'-terminal non-coding region of the hepatitis C virus genome. Other combinations produced more false negative results. Three different groups of anti-hepatitis C virus antibody positive individuals had markedly different viraemia patterns: Hepatitis C virus RNA was detected in the sera of only 10% of anti-hepatitis C virus antibody positive blood donors, but in 90% of anti-hepatitis C virus antibody positive patients with clinically manifest hepatitis C, and 90% of anti-hepatitis C virus antibody positive haemophiliacs who had received plasma products in the past which had not been virus-inactivated. No hepatitis C virus RNA could be detected in the sera of 450 anti-hepatitis C virus antibody negative blood donors with elevated serum alanine aminotransferase catalytic concentrations."} {"id": "PMID:1283342", "title": "Epitope mapping of human factor VIII inhibitor antibodies by site-directed mutagenesis of a factor VIII polypeptide.", "content": "Previous epitope mapping studies of human factor VIII (FVIII) inhibitor antibodies with heavy chain specificity localized epitopes to the amino-terminal half of the FVIII A2 domain. In this report we have used unidirectional deletion analysis and site-directed mutagenesis to identify a minimum length polypeptide and amino acid residues that contribute to the FVIII conformation recognized by these antibodies. Bacterial expression plasmids were exploited to demonstrate that a FVIII polypeptide of approximately 150 residues is required to generate a common heavy chain epitope(s). Another series of plasmids were constructed that synthesize: a FVIII polypeptide containing an internal deletion; four polypeptides with single residue substitutions; two polypeptides with triple residue changes; and a quadruple amino acid replacement within one polypeptide. The relative reactivities of the wild-type and mutant FVIII polypeptides were tested by immunoblotting, inhibitor neutralization assays and ELISA with a variety of human FVIII inhibitor auto- and alloantibodies. These techniques illustrate that the internal deletion mutant and one of the relatively conservative amino acid substitution triple mutants, mutant 389, resulted in significantly decreased immunoreactivity. The data identify FVIII Glu389,390,391 as three critical components of an epitope for human FVIII inhibitor antibodies and identify a major inhibitory epitope involved in the immune response to FVIII.", "contents": "Epitope mapping of human factor VIII inhibitor antibodies by site-directed mutagenesis of a factor VIII polypeptide. Previous epitope mapping studies of human factor VIII (FVIII) inhibitor antibodies with heavy chain specificity localized epitopes to the amino-terminal half of the FVIII A2 domain. In this report we have used unidirectional deletion analysis and site-directed mutagenesis to identify a minimum length polypeptide and amino acid residues that contribute to the FVIII conformation recognized by these antibodies. Bacterial expression plasmids were exploited to demonstrate that a FVIII polypeptide of approximately 150 residues is required to generate a common heavy chain epitope(s). Another series of plasmids were constructed that synthesize: a FVIII polypeptide containing an internal deletion; four polypeptides with single residue substitutions; two polypeptides with triple residue changes; and a quadruple amino acid replacement within one polypeptide. The relative reactivities of the wild-type and mutant FVIII polypeptides were tested by immunoblotting, inhibitor neutralization assays and ELISA with a variety of human FVIII inhibitor auto- and alloantibodies. These techniques illustrate that the internal deletion mutant and one of the relatively conservative amino acid substitution triple mutants, mutant 389, resulted in significantly decreased immunoreactivity. The data identify FVIII Glu389,390,391 as three critical components of an epitope for human FVIII inhibitor antibodies and identify a major inhibitory epitope involved in the immune response to FVIII."} {"id": "PMID:1283343", "title": "Aprotinin inhibits platelet adhesion to endothelial cells.", "content": "Studies were conducted to assess the effect of the serine protease inhibitor aprotinin on platelet adherence to both thrombin-stimulated and unstimulated human umbilical vein endothelial cells. Aprotinin treatment reduced significantly the adherence of platelets to endothelium pretreated or not with thrombin. In addition, aprotinin similarly reduced the adherence of platelets to plastic or collagen-coated tissue culture wells suggesting that the main site of action of the drug in this system is on the platelets. The role of endothelium-derived relaxing factor (EDRF; nitric oxide) in these platelet-endothelium reactions was investigated by prior incubation of both platelets and endothelial cells with NG-monomethyl-L-arginine (L-NMMA) which prevents the production of nitric oxide. The results demonstrated that nitric oxide was a significant inhibitor of the thrombin-induced platelet adherence in this assay system. Treatment with aprotinin in the presence or absence of L-NMMA reduced adherence of platelets to equivalent levels suggesting that aprotinin acts directly on the platelets via a mechanism that is EDRF-independent, to inhibit adherence.", "contents": "Aprotinin inhibits platelet adhesion to endothelial cells. Studies were conducted to assess the effect of the serine protease inhibitor aprotinin on platelet adherence to both thrombin-stimulated and unstimulated human umbilical vein endothelial cells. Aprotinin treatment reduced significantly the adherence of platelets to endothelium pretreated or not with thrombin. In addition, aprotinin similarly reduced the adherence of platelets to plastic or collagen-coated tissue culture wells suggesting that the main site of action of the drug in this system is on the platelets. The role of endothelium-derived relaxing factor (EDRF; nitric oxide) in these platelet-endothelium reactions was investigated by prior incubation of both platelets and endothelial cells with NG-monomethyl-L-arginine (L-NMMA) which prevents the production of nitric oxide. The results demonstrated that nitric oxide was a significant inhibitor of the thrombin-induced platelet adherence in this assay system. Treatment with aprotinin in the presence or absence of L-NMMA reduced adherence of platelets to equivalent levels suggesting that aprotinin acts directly on the platelets via a mechanism that is EDRF-independent, to inhibit adherence."} {"id": "PMID:1283345", "title": "Ion channels on synaptic vesicle membranes studied by planar lipid bilayer method.", "content": "An anion selective channel and three types of cation selective channels were found in planar lipid bilayers incorporating synaptic vesicles from rat brains. In asymmetric KCl solutions (cis: 300 mM/trans: 150 mM), the anion selective channel showed a single-channel conductance of 94 pS and was inactivated by negative voltages and by 4-acetoamido-4'-isothiocyanostilbene-2,2'-disulfonic acid disodium salt (SITS). In the same solution, single-channel conductances of three types of cation selective channels were 250 pS (Type 1), 248 pS (Type 2), and 213 pS (Type 3), respectively. These channels resembled one another in single-channel conductances but were different in gating behaviors. Type 1 channel, which was most frequently observed, had a remarkable subconducting state (175 pS). Type 2 channel had a flickering state that increased as the potential became more positive, and a long inactive state that increased as the potentials were more negative. Type 3 channel, which was also sensitive to the potentials, had the open-channel probability increased as the potential became more positive.", "contents": "Ion channels on synaptic vesicle membranes studied by planar lipid bilayer method. An anion selective channel and three types of cation selective channels were found in planar lipid bilayers incorporating synaptic vesicles from rat brains. In asymmetric KCl solutions (cis: 300 mM/trans: 150 mM), the anion selective channel showed a single-channel conductance of 94 pS and was inactivated by negative voltages and by 4-acetoamido-4'-isothiocyanostilbene-2,2'-disulfonic acid disodium salt (SITS). In the same solution, single-channel conductances of three types of cation selective channels were 250 pS (Type 1), 248 pS (Type 2), and 213 pS (Type 3), respectively. These channels resembled one another in single-channel conductances but were different in gating behaviors. Type 1 channel, which was most frequently observed, had a remarkable subconducting state (175 pS). Type 2 channel had a flickering state that increased as the potential became more positive, and a long inactive state that increased as the potentials were more negative. Type 3 channel, which was also sensitive to the potentials, had the open-channel probability increased as the potential became more positive."} {"id": "PMID:1283346", "title": "Statistical properties predicted by the ball and chain model of channel inactivation.", "content": "It has been proposed that part of a voltage gated channel is a tethered ball and that inactivation occurs when this wandering ball binds to a site in the channel. In order to be able to quantitatively test this model by comparison to experiments we developed analytical solutions and numerical simulations of the distribution of times it takes the ball to reach the binding site when the motion of the ball is random and when it is also influenced by a directed force. If the motion of the ball is one-dimensional, at long times this distribution is a single exponential with a rate constant that is inversely proportional to the square of the length of the chain and does not depend on the starting position of the ball. This dependence on the chain length is not significantly altered if there are short range electrical forces between the ball and its binding site. These predictions suggest that to confirm the validity of this model additional experiments should be done to more precisely determine the form of this distribution and its dependence on the length of the chain.", "contents": "Statistical properties predicted by the ball and chain model of channel inactivation. It has been proposed that part of a voltage gated channel is a tethered ball and that inactivation occurs when this wandering ball binds to a site in the channel. In order to be able to quantitatively test this model by comparison to experiments we developed analytical solutions and numerical simulations of the distribution of times it takes the ball to reach the binding site when the motion of the ball is random and when it is also influenced by a directed force. If the motion of the ball is one-dimensional, at long times this distribution is a single exponential with a rate constant that is inversely proportional to the square of the length of the chain and does not depend on the starting position of the ball. This dependence on the chain length is not significantly altered if there are short range electrical forces between the ball and its binding site. These predictions suggest that to confirm the validity of this model additional experiments should be done to more precisely determine the form of this distribution and its dependence on the length of the chain."} {"id": "PMID:1283347", "title": "Modeling the ion channel structure of cecropin.", "content": "Atomic-scale computer models were developed for how cecropin peptides may assemble in membranes to form two types of ion channels. The models are based on experimental data and physiochemical principles. Initially, cecropin peptides, in a helix-bend-helix motif, were arranged as antiparallel dimers to position conserved residues of adjacent monomers in contact. The dimers were postulated to bind to the membrane with the NH2-terminal helices sunken into the head-group layer and the COOH-terminal helices spanning the hydrophobic core. This causes a thinning of the top lipid layer of the membrane. A collection of the membrane bound dimers were then used to form the type I channel structure, with the pore formed by the transmembrane COOH-terminal helices. Type I channels were then assembled into a hexagonal lattice to explain the large number of peptides that bind to the bacterium. A concerted conformational change of a type I channel leads to the larger type II channel, in which the pore is formed by the NH2-terminal helices. By having the dimers move together, the NH2-terminal helices are inserted into the hydrophobic core without having to desolvate the charged residues. It is also shown how this could bring lipid head-groups into the pore lining.", "contents": "Modeling the ion channel structure of cecropin. Atomic-scale computer models were developed for how cecropin peptides may assemble in membranes to form two types of ion channels. The models are based on experimental data and physiochemical principles. Initially, cecropin peptides, in a helix-bend-helix motif, were arranged as antiparallel dimers to position conserved residues of adjacent monomers in contact. The dimers were postulated to bind to the membrane with the NH2-terminal helices sunken into the head-group layer and the COOH-terminal helices spanning the hydrophobic core. This causes a thinning of the top lipid layer of the membrane. A collection of the membrane bound dimers were then used to form the type I channel structure, with the pore formed by the transmembrane COOH-terminal helices. Type I channels were then assembled into a hexagonal lattice to explain the large number of peptides that bind to the bacterium. A concerted conformational change of a type I channel leads to the larger type II channel, in which the pore is formed by the NH2-terminal helices. By having the dimers move together, the NH2-terminal helices are inserted into the hydrophobic core without having to desolvate the charged residues. It is also shown how this could bring lipid head-groups into the pore lining."} {"id": "PMID:1283349", "title": "Laparoscopic cholecysto-jejunostomy for obstructing pancreatic cancer: technique and report of two cases.", "content": "Laparoscopic cholecysto-jejunostomy was performed on two patients with obstructive jaundice due to a mass in the head of the pancreas. Diagnostic studies included CT scan, ERCP, arteriogram, and percutaneous needle aspiration cytology. Both patients recovered without event and were discharged after 4 days.", "contents": "Laparoscopic cholecysto-jejunostomy for obstructing pancreatic cancer: technique and report of two cases. Laparoscopic cholecysto-jejunostomy was performed on two patients with obstructive jaundice due to a mass in the head of the pancreas. Diagnostic studies included CT scan, ERCP, arteriogram, and percutaneous needle aspiration cytology. Both patients recovered without event and were discharged after 4 days."} {"id": "PMID:1283350", "title": "Stochastic models for ion channels: introduction and bibliography.", "content": "This paper provides an introduction to and overview of the use of stochastic models and statistical analysis in the study of ion channels in cell membranes. An extensive bibliography is included.", "contents": "Stochastic models for ion channels: introduction and bibliography. This paper provides an introduction to and overview of the use of stochastic models and statistical analysis in the study of ion channels in cell membranes. An extensive bibliography is included."} {"id": "PMID:1283348", "title": "Coexistence of hyperthyroidism and ulcerative colitis: report of 4 cases and a review of the literature.", "content": "Four cases of coexisting hyperthyroidism and ulcerative colitis are presented. In two patients the diseases appeared simultaneously, in one the diagnosis of ulcerative colitis preceded the diagnosis of hyperthyroidism, while in the fourth the diagnosis of hyperthyroidism preceded the diagnosis of ulcerative colitis. Hyperthyroidism intensifies the symptoms of ulcerative colitis and impairs response to therapy. Treatment of both diseases should be conservative. There is no clear explanation for the concurrent existence of the two diseases, although immunological mechanisms seem to play the most significant role. The clinician must bear in mind that coexistence of hyperthyroidism and ulcerative colitis in some patients, although infrequent, nevertheless is a reality, which obviously is very important for the patient's outcome.", "contents": "Coexistence of hyperthyroidism and ulcerative colitis: report of 4 cases and a review of the literature. Four cases of coexisting hyperthyroidism and ulcerative colitis are presented. In two patients the diseases appeared simultaneously, in one the diagnosis of ulcerative colitis preceded the diagnosis of hyperthyroidism, while in the fourth the diagnosis of hyperthyroidism preceded the diagnosis of ulcerative colitis. Hyperthyroidism intensifies the symptoms of ulcerative colitis and impairs response to therapy. Treatment of both diseases should be conservative. There is no clear explanation for the concurrent existence of the two diseases, although immunological mechanisms seem to play the most significant role. The clinician must bear in mind that coexistence of hyperthyroidism and ulcerative colitis in some patients, although infrequent, nevertheless is a reality, which obviously is very important for the patient's outcome."} {"id": "PMID:1283351", "title": "Sequence-specific cleavage of single-stranded DNA by oligonucleotides conjugated to bleomycin.", "content": "Cleavage of a single-stranded DNA fragment by complementary oligonucleotides conjugated to bleomycin A5 has been investigated. The conjugates efficiently cleave the DNA at the GT sequences near the oligonucleotide binding site. The temperature dependence of the reaction and the composition of the degradation products indicate that the oligonucleotide-linked bleomycin attacks the available double-stranded DNA regions within the oligonucleotide-DNA duplex and in the hairpin DNA region in the vicinity of the carrier oligonucleotide binding site.", "contents": "Sequence-specific cleavage of single-stranded DNA by oligonucleotides conjugated to bleomycin. Cleavage of a single-stranded DNA fragment by complementary oligonucleotides conjugated to bleomycin A5 has been investigated. The conjugates efficiently cleave the DNA at the GT sequences near the oligonucleotide binding site. The temperature dependence of the reaction and the composition of the degradation products indicate that the oligonucleotide-linked bleomycin attacks the available double-stranded DNA regions within the oligonucleotide-DNA duplex and in the hairpin DNA region in the vicinity of the carrier oligonucleotide binding site."} {"id": "PMID:1283353", "title": "A 4D HCCH-TOCSY experiment for assigning the side chain 1H and 13C resonances of proteins.", "content": "A 4D HCCH-TOCSY experiment is described for correlating and assigning the 1H and 13C resonances of protein amino acid side chains that has several advantages over 3D versions of the experiment. In many cases, both the 1H and 13C chemical shifts can be obtained in the 4D experiment from a simple inspection of the 13C(omega 3), 1H(omega 4) planes extracted at the 1H alpha(omega 1)/13C alpha(omega 2) chemical shifts. Together with the 3D and 4D triple resonance experiments, this allows sequence-specific assignments to be obtained. In addition, the increased resolution of the 4D experiment compared to its 3D counterpart allows automation of resonance assignments.", "contents": "A 4D HCCH-TOCSY experiment for assigning the side chain 1H and 13C resonances of proteins. A 4D HCCH-TOCSY experiment is described for correlating and assigning the 1H and 13C resonances of protein amino acid side chains that has several advantages over 3D versions of the experiment. In many cases, both the 1H and 13C chemical shifts can be obtained in the 4D experiment from a simple inspection of the 13C(omega 3), 1H(omega 4) planes extracted at the 1H alpha(omega 1)/13C alpha(omega 2) chemical shifts. Together with the 3D and 4D triple resonance experiments, this allows sequence-specific assignments to be obtained. In addition, the increased resolution of the 4D experiment compared to its 3D counterpart allows automation of resonance assignments."} {"id": "PMID:1283354", "title": "Differential induction and suppression of potato 3-hydroxy-3-methylglutaryl coenzyme A reductase genes in response to Phytophthora infestans and to its elicitor arachidonic acid.", "content": "Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is essential for the biosynthesis of sesquiterpenoid phytoalexins and steroid derivatives in Solanaceous plants following stresses imposed by wounding and pathogen infection. To better understand this complex step in stress-responsive isoprenoid synthesis, we isolated three classes of cDNAS encoding HMGR (hmg1, hmg2, and hmg3) from a potato tuber library using a probe derived from an Arabidopsis HMGR cDNA. The potato cDNAs had extensive homology in portions of the protein coding regions but had low homology in the 3' untranslated regions. RNA gel blot analyses using gene-specific probes showed that hmg1 was strongly induced in tuber tissue by wounding, but the wound induction was strongly suppressed by treatment of the tissue with the fungal elicitor arachidonic acid or by inoculation with an incompatible or compatible race of the fungal pathogen Phytophtora infestans. The hmg2 and hmg3 mRNAs also accumulated in response to wounding, but in contrast to hmg1, these mRNAs were strongly enhanced by arachidonic acid or inoculation. Inoculation with a compatible race of P. infestans resulted in similar patterns in HMGR gene expression of hmg2 and hmg3 except that the magnitude and rate of the changes in mRNA levels were reduced relative to the incompatible interaction. The differential regulation of members of the HMGR gene family may explain in part the previously reported changes in HMGR enzyme activities following wounding and elicitor treatment. The suppression of hmg1 and the enhancement of hmg2 and hmg3 transcript levels following elicitor treatment or inoculation with the incompatible race parallel the suppression in steroid and stimulation of sesquiterpenoid accumulations observed in earlier investigations. The results are discussed in relation to the hypothesis that there are discrete organizational channels for sterol and sesquiterpene biosynthesis in potato and other Solanaceous species.", "contents": "Differential induction and suppression of potato 3-hydroxy-3-methylglutaryl coenzyme A reductase genes in response to Phytophthora infestans and to its elicitor arachidonic acid. Induction of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) is essential for the biosynthesis of sesquiterpenoid phytoalexins and steroid derivatives in Solanaceous plants following stresses imposed by wounding and pathogen infection. To better understand this complex step in stress-responsive isoprenoid synthesis, we isolated three classes of cDNAS encoding HMGR (hmg1, hmg2, and hmg3) from a potato tuber library using a probe derived from an Arabidopsis HMGR cDNA. The potato cDNAs had extensive homology in portions of the protein coding regions but had low homology in the 3' untranslated regions. RNA gel blot analyses using gene-specific probes showed that hmg1 was strongly induced in tuber tissue by wounding, but the wound induction was strongly suppressed by treatment of the tissue with the fungal elicitor arachidonic acid or by inoculation with an incompatible or compatible race of the fungal pathogen Phytophtora infestans. The hmg2 and hmg3 mRNAs also accumulated in response to wounding, but in contrast to hmg1, these mRNAs were strongly enhanced by arachidonic acid or inoculation. Inoculation with a compatible race of P. infestans resulted in similar patterns in HMGR gene expression of hmg2 and hmg3 except that the magnitude and rate of the changes in mRNA levels were reduced relative to the incompatible interaction. The differential regulation of members of the HMGR gene family may explain in part the previously reported changes in HMGR enzyme activities following wounding and elicitor treatment. The suppression of hmg1 and the enhancement of hmg2 and hmg3 transcript levels following elicitor treatment or inoculation with the incompatible race parallel the suppression in steroid and stimulation of sesquiterpenoid accumulations observed in earlier investigations. The results are discussed in relation to the hypothesis that there are discrete organizational channels for sterol and sesquiterpene biosynthesis in potato and other Solanaceous species."} {"id": "PMID:1283352", "title": "Transillumination guided cyclocryotherapy in the treatment of secondary glaucoma.", "content": "A consecutive series of 38 eyes of 35 glaucoma patients treated with transillumination guided cyclocryotherapy (CCT) either to obtain pain relief or to achieve IOP control was studied at Helsinki University Eye Hospital. Transillumination was used to guide the applications to the correct site. The follow-up range was 1-43 months (mean 9 months). Pretreatment IOP was 39 +/- 13 mm Hg and postoperative 26 +/- 16 mm Hg (mean +/- SD). Twenty-three eyes underwent one and 15 eyes 2-5 procedures. IOP control (IOP 9-23 mm Hg) was achieved in 50%. The response was more favorable in eyes without iris neovascularisation (59% achieved IOP control) than in eyes with neovascular glaucoma (38% achieved IOP control). The best response was achieved in eyes with chronic uveitis (5/7 eyes achieved IOP control). Repeated procedures improved the IOP control rate. Hypotony (IOP < 9 mm Hg) without clinical signs of phthisis occurred in three eyes (8%). Thirteen eyes needed primarily pain relief and 92% achieved it. Postoperatively vision was better in 8%, unchanged in 37% and worse in 55%. Visual acuity was 0.05 or better in nine eyes pretreatment and in eight eyes after treatment.", "contents": "Transillumination guided cyclocryotherapy in the treatment of secondary glaucoma. A consecutive series of 38 eyes of 35 glaucoma patients treated with transillumination guided cyclocryotherapy (CCT) either to obtain pain relief or to achieve IOP control was studied at Helsinki University Eye Hospital. Transillumination was used to guide the applications to the correct site. The follow-up range was 1-43 months (mean 9 months). Pretreatment IOP was 39 +/- 13 mm Hg and postoperative 26 +/- 16 mm Hg (mean +/- SD). Twenty-three eyes underwent one and 15 eyes 2-5 procedures. IOP control (IOP 9-23 mm Hg) was achieved in 50%. The response was more favorable in eyes without iris neovascularisation (59% achieved IOP control) than in eyes with neovascular glaucoma (38% achieved IOP control). The best response was achieved in eyes with chronic uveitis (5/7 eyes achieved IOP control). Repeated procedures improved the IOP control rate. Hypotony (IOP < 9 mm Hg) without clinical signs of phthisis occurred in three eyes (8%). Thirteen eyes needed primarily pain relief and 92% achieved it. Postoperatively vision was better in 8%, unchanged in 37% and worse in 55%. Visual acuity was 0.05 or better in nine eyes pretreatment and in eight eyes after treatment."} {"id": "PMID:1283355", "title": "Acute onset of rubeosis iridis after diabetic vitrectomy can indicate peripheral traction retinal detachment.", "content": "Acute onset or exacerbation of rubeosis iridis associated with peripheral retinal detachment after vitrectomy represents a rare but serious complication of advanced diabetic retinopathy that indicates a poor prognosis. The clinical features, surgical procedures, and anatomical and functional results for a series of 13 eyes presenting with this complication are reported. In addition to rubeosis iridis and peripheral retinal detachment, anterior hyaloidal fibrovascular proliferation (APH) was also present in 10 eyes. All eyes had undergone one or more previous vitrectomies for diabetic complications such as nonclearing vitreous hemorrhage and traction retinal detachment. Treatment modalities for iris neovascularization and peripheral retinal detachment included reattachment procedures with an encircling band, peripheral membrane peeling, and, if necessary, peripheral retinectomy. Peripheral coagulation therapy was performed in all eyes. Eight eyes received an intraocular silicone-oil tamponade. Early results (4 weeks post-surgery) showed regression or stabilization of rubeosis iridis in all eyes. Later results (mean, 9 months post-surgery) revealed nine eyes with stabilized anterior ocular neovascularization and reattachment of the retina. Four eyes were anatomic failures due to recurrent rubeosis iridis/AHP or traction retinal detachment, and three of them also developed ocular hypotony. None of the eyes has thus far been lost as a result of neovascular glaucoma or painful phthisis. Ambulatory vision was retained in ten eyes, but function was limited to a low level as a result of the underlying ischemic disease. Immediate reattachment surgery in combination with anterior/peripheral coagulation therapy was shown to be an effective measure for controlling iris neovascular activity in eyes afflicted with acute anterior ocular neovascularization.", "contents": "Acute onset of rubeosis iridis after diabetic vitrectomy can indicate peripheral traction retinal detachment. Acute onset or exacerbation of rubeosis iridis associated with peripheral retinal detachment after vitrectomy represents a rare but serious complication of advanced diabetic retinopathy that indicates a poor prognosis. The clinical features, surgical procedures, and anatomical and functional results for a series of 13 eyes presenting with this complication are reported. In addition to rubeosis iridis and peripheral retinal detachment, anterior hyaloidal fibrovascular proliferation (APH) was also present in 10 eyes. All eyes had undergone one or more previous vitrectomies for diabetic complications such as nonclearing vitreous hemorrhage and traction retinal detachment. Treatment modalities for iris neovascularization and peripheral retinal detachment included reattachment procedures with an encircling band, peripheral membrane peeling, and, if necessary, peripheral retinectomy. Peripheral coagulation therapy was performed in all eyes. Eight eyes received an intraocular silicone-oil tamponade. Early results (4 weeks post-surgery) showed regression or stabilization of rubeosis iridis in all eyes. Later results (mean, 9 months post-surgery) revealed nine eyes with stabilized anterior ocular neovascularization and reattachment of the retina. Four eyes were anatomic failures due to recurrent rubeosis iridis/AHP or traction retinal detachment, and three of them also developed ocular hypotony. None of the eyes has thus far been lost as a result of neovascular glaucoma or painful phthisis. Ambulatory vision was retained in ten eyes, but function was limited to a low level as a result of the underlying ischemic disease. Immediate reattachment surgery in combination with anterior/peripheral coagulation therapy was shown to be an effective measure for controlling iris neovascular activity in eyes afflicted with acute anterior ocular neovascularization."} {"id": "PMID:1283356", "title": "Treatment of AIDS-related non-Hodgkin's lymphoma with a twelve week chemotherapy program.", "content": "Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL.", "contents": "Treatment of AIDS-related non-Hodgkin's lymphoma with a twelve week chemotherapy program. Current treatment options for acquired-immunodeficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) are unsatisfactory because of excessive toxicity rates and frequent recurrence of lymphoma. In this phase II study, we evaluated a novel 12 week chemotherapy program with respect to feasibility, toxicity and therapeutic results. Thirty HIV-seropositive patients with intermediate grade or small non-cleaved cell NHL received a 12 week program of weekly intravenous and oral chemotherapy consisting of etoposide, adriamycin, cyclophosphamide, bleomycin, vincristine, methotrexate and prednisone as well as biweekly intrathecal cytosine arabinoside. Prophylaxis against Pneumocystis carinii pneumonia (PCP) and candida were given routinely. The overall objective response rate was 73% with 33% complete responders. The time to progression for those stable or responding was 9.4 months. Five of 10 complete responders are well and free of disease 13.2 to 24.5 months from diagnosis. Median survival for the 30 patients was 8.1 months. NHL was the most common cause of death (13/22); opportunistic infection caused only one death (cryptococcal meningitis). Only 1 case of PCP occurred. The major toxicity was neutropenia. In conclusion this regimen resulted in response rates similar to other reports with acceptable toxicity and a very low incidence of PCP. Relapse of NHL remains a major challenge, however, and further studies are needed. Routine PCP prophylaxis should be incorporated into new trials of therapy for AIDS-related NHL."} {"id": "PMID:1283357", "title": "Systemic lupus erythematosus and chronic lymphocytic leukemia: rare coexistence in three patients, with comments on pathogenesis.", "content": "We describe three patients with coexistent chronic lymphatic leukemia (CLL) and systemic lupus erythematosus (SLE). In two patients, the CLL was present before or coexistent with the SLE when the SLE was diagnosed, while in the third, the CLL developed 5 years after the diagnosis of SLE was first made. Although the association of autoimmune diseases and lymphoproliferative disorders is well established, only a few patients with coexistent CLL and concomitant SLE have been reported. The possible pathogenesis of this rare association is discussed.", "contents": "Systemic lupus erythematosus and chronic lymphocytic leukemia: rare coexistence in three patients, with comments on pathogenesis. We describe three patients with coexistent chronic lymphatic leukemia (CLL) and systemic lupus erythematosus (SLE). In two patients, the CLL was present before or coexistent with the SLE when the SLE was diagnosed, while in the third, the CLL developed 5 years after the diagnosis of SLE was first made. Although the association of autoimmune diseases and lymphoproliferative disorders is well established, only a few patients with coexistent CLL and concomitant SLE have been reported. The possible pathogenesis of this rare association is discussed."} {"id": "PMID:1283358", "title": "Rapid quantitation by PCR of endomycorrhizal fungi colonizing roots.", "content": "The VANS1/NS21 primer pair is useful for specifically amplifying a 550-bp ribosomal (r) DNA fragment from arbuscular endomycorrhizal fungi, directly from colonized root extracts. A procedure to quantitate these obligatory biotrophs rapidly, based on competitive PCR, was developed by constructing a suitable internal standard to be used with these primers. A 130-bp deletion in the Glomus mossae VANS1/NS21 amplified rDNA fragment was produced by amplifying separately external portions of that fragment, followed by ligation and amplification using the original external primers. When this deleted fragment was added to G. mossae rDNA, amplification using VANS1/NS21 primers yielded the two expected products of 430 bp and 550 bp, respectively, resolved by agarose electrophoresis. This fragment was cloned into the pCL1920 plasmid, a low-copy-number vector (five copies per cell), and mixed with the roots to be analyzed. This provides for a rapid quantitative assay because both steps--extraction of DNA from colonized roots and PCR amplification--are taken into account by the same internal standard. Using this procedure, a sample of colonized leek roots (Allium porum x Glomus vesiculiferum) was shown to contain 5 x 10(4) copies of arbuscular endomycorrhizal fungi rDNA genes per milligram of fresh weight.", "contents": "Rapid quantitation by PCR of endomycorrhizal fungi colonizing roots. The VANS1/NS21 primer pair is useful for specifically amplifying a 550-bp ribosomal (r) DNA fragment from arbuscular endomycorrhizal fungi, directly from colonized root extracts. A procedure to quantitate these obligatory biotrophs rapidly, based on competitive PCR, was developed by constructing a suitable internal standard to be used with these primers. A 130-bp deletion in the Glomus mossae VANS1/NS21 amplified rDNA fragment was produced by amplifying separately external portions of that fragment, followed by ligation and amplification using the original external primers. When this deleted fragment was added to G. mossae rDNA, amplification using VANS1/NS21 primers yielded the two expected products of 430 bp and 550 bp, respectively, resolved by agarose electrophoresis. This fragment was cloned into the pCL1920 plasmid, a low-copy-number vector (five copies per cell), and mixed with the roots to be analyzed. This provides for a rapid quantitative assay because both steps--extraction of DNA from colonized roots and PCR amplification--are taken into account by the same internal standard. Using this procedure, a sample of colonized leek roots (Allium porum x Glomus vesiculiferum) was shown to contain 5 x 10(4) copies of arbuscular endomycorrhizal fungi rDNA genes per milligram of fresh weight."} {"id": "PMID:1283360", "title": "Effects of radiation and 4-hydroperoxycyclophosphamide on production of G- and GM-CSF by stromal cells.", "content": "The effects of in vitro radiation and exposure to 4-hydroperoxycyclophosphamide (4-HC) on the production of G- and GM-CSF by different components of the human hematopoietic microenvironment are described. The marrow microenvironment is composed of fibroblasts, endothelial cells, macrophages, and adipocytes. To study the effects of radiation/4-HC on colony-stimulating factor (CSF) production by stromal cells, confluent layers of umbilical cord endothelial cells (EC), marrow fibroblasts (MF), and heterogeneous adherent layers (HAL) derived from long-term marrow cultures were established. These layers were exposed to radiation up to 3000 cGy and/or 100 mumol/ml of 4-HC and subsequently stimulated with IL-1 beta on day 0, 7, or 14 after radiation/4-HC. Following IL-1 exposure conditioned medium (CM) was collected and G- and GM-CSF levels were measured by ELISA and their ability to support colony formation was assessed. G- and GM-CSF levels after exposure to 4-HC and radiation were 12,460 +/- 172 pg/ml and 2268 +/- 160 pg/ml for EC, 2214 +/- 94 pg/ml and 263 +/- pg/ml for MF, and 3168 +/- 316 pg/ml and 356 +/- 34 pg/ml for HALs, respectively. For each cell group there was no significant difference between levels obtained without exposure and levels after exposure to 4-HC and/or radiation (p > 0.6). Comparison of levels obtained from different cell groups showed significant differences with EC media being the highest (p < 0.0001). To test the activity of these measured factors, CM of different sources was used in colony assays of CD 34+ cord blood progenitors.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Effects of radiation and 4-hydroperoxycyclophosphamide on production of G- and GM-CSF by stromal cells. The effects of in vitro radiation and exposure to 4-hydroperoxycyclophosphamide (4-HC) on the production of G- and GM-CSF by different components of the human hematopoietic microenvironment are described. The marrow microenvironment is composed of fibroblasts, endothelial cells, macrophages, and adipocytes. To study the effects of radiation/4-HC on colony-stimulating factor (CSF) production by stromal cells, confluent layers of umbilical cord endothelial cells (EC), marrow fibroblasts (MF), and heterogeneous adherent layers (HAL) derived from long-term marrow cultures were established. These layers were exposed to radiation up to 3000 cGy and/or 100 mumol/ml of 4-HC and subsequently stimulated with IL-1 beta on day 0, 7, or 14 after radiation/4-HC. Following IL-1 exposure conditioned medium (CM) was collected and G- and GM-CSF levels were measured by ELISA and their ability to support colony formation was assessed. G- and GM-CSF levels after exposure to 4-HC and radiation were 12,460 +/- 172 pg/ml and 2268 +/- 160 pg/ml for EC, 2214 +/- 94 pg/ml and 263 +/- pg/ml for MF, and 3168 +/- 316 pg/ml and 356 +/- 34 pg/ml for HALs, respectively. For each cell group there was no significant difference between levels obtained without exposure and levels after exposure to 4-HC and/or radiation (p > 0.6). Comparison of levels obtained from different cell groups showed significant differences with EC media being the highest (p < 0.0001). To test the activity of these measured factors, CM of different sources was used in colony assays of CD 34+ cord blood progenitors.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283362", "title": "Antibodies to the rat substance P receptor: production and characterization.", "content": "1. A protein A-rat substance P receptor (SPR) fusion protein was genetically engineered and used as an immunogen to raise a polyclonal antiserum to the SPR. The fusion protein was expressed in Escherichia coli driven by the heat-inducible lambda promoter (lambda Pr). 2. The fusion protein was purified using an IgG-Sepharose column, which specifically binds proteins containing the protein A moiety. The IgG fraction obtained after the immunization was cleaved to produce Fab fragments, which were subsequently purified using a fusion protein affinity column. The serum (anti-SPR Fab serum) was analyzed by fluorescence-activated cell sorting (FACS) and immunohistochemistry on both a constitutive cell line for the SPR (AR42J) and a cell line transfected with the SPR (KNRKSPR). 3. Specificity of the antiserum for SPR was confirmed by immunohistochemistry on cells using antiserum that had been preincubated with the protein A fusion protein (blocked). 4. The Ca2+ signal normally observed on stimulation of SPR with SP in AR42J cells and SP binding to KNRKSPR cells was shown to be diminished in the presence of anti-SPR Fab serum. SPR from both cell lines was immunoprecipitated using the anti-SPR Fab serum. The antiserum itself did not induce intracellular Ca2+ mobilization normally observed when cells were incubated with SP. 5. This specific SPR antiserum will be a useful tool to investigate further the mechanisms of SP/SPR interactions.", "contents": "Antibodies to the rat substance P receptor: production and characterization. 1. A protein A-rat substance P receptor (SPR) fusion protein was genetically engineered and used as an immunogen to raise a polyclonal antiserum to the SPR. The fusion protein was expressed in Escherichia coli driven by the heat-inducible lambda promoter (lambda Pr). 2. The fusion protein was purified using an IgG-Sepharose column, which specifically binds proteins containing the protein A moiety. The IgG fraction obtained after the immunization was cleaved to produce Fab fragments, which were subsequently purified using a fusion protein affinity column. The serum (anti-SPR Fab serum) was analyzed by fluorescence-activated cell sorting (FACS) and immunohistochemistry on both a constitutive cell line for the SPR (AR42J) and a cell line transfected with the SPR (KNRKSPR). 3. Specificity of the antiserum for SPR was confirmed by immunohistochemistry on cells using antiserum that had been preincubated with the protein A fusion protein (blocked). 4. The Ca2+ signal normally observed on stimulation of SPR with SP in AR42J cells and SP binding to KNRKSPR cells was shown to be diminished in the presence of anti-SPR Fab serum. SPR from both cell lines was immunoprecipitated using the anti-SPR Fab serum. The antiserum itself did not induce intracellular Ca2+ mobilization normally observed when cells were incubated with SP. 5. This specific SPR antiserum will be a useful tool to investigate further the mechanisms of SP/SPR interactions."} {"id": "PMID:1283363", "title": "Monoamine neurotransmitters and their metabolites in brain regions in Alzheimer's disease: a postmortem study.", "content": "1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD.", "contents": "Monoamine neurotransmitters and their metabolites in brain regions in Alzheimer's disease: a postmortem study. 1. Concentrations of the neurotransmitter amines noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) and the acid metabolites homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were determined in four regions of postmortem brains of demented patients with or without Alzheimer's disease (AD). 2. NA was deficient in the temporal cortex (BA 21) of AD, but not of non-AD, patients. 3. Caudate, in particular, had an impaired dopaminergic system in AD patients, with low HVA levels. 4. In all regions investigated [amygdala, caudate, putamen, temporal cortex (BA 21)] 5-HT was significantly depleted in AD patients, and 5-HIAA was also depleted in amygdala and caudate. 5. These results indicate that neurotransmitter systems other than cholinergic systems are also widely affected in AD and suggest that these deficits may also play an important role in determining the symptomatology of AD."} {"id": "PMID:1283364", "title": "Mapping of monoclonal antibody epitopes in the nucleolar protein fibrillarin (B-36) of Physarum polycephalum.", "content": "We have mapped the epitopes for nine monoclonal antibodies raised against the nucleolar protein fibrillarin of the slime mold Physarum polycephalum. This has been done using a combination of specific chemical and enzymatic cleavage, Western blotting and partial sequencing of fragments. Cleavage with cyanogen bromide reveals four prominent methionine cleavage sites within the protein. Western blotting shows that none of the monoclonal antibody epitopes are dependent on long range interactions. Eight highly-conserved epitopes are clustered in the carboxy terminal half of the protein, while a single less-conserved epitope (for monoclonal antibody P1G12) is located at the amino terminus and appears to lie within the Gly/DMA/Phe domain.", "contents": "Mapping of monoclonal antibody epitopes in the nucleolar protein fibrillarin (B-36) of Physarum polycephalum. We have mapped the epitopes for nine monoclonal antibodies raised against the nucleolar protein fibrillarin of the slime mold Physarum polycephalum. This has been done using a combination of specific chemical and enzymatic cleavage, Western blotting and partial sequencing of fragments. Cleavage with cyanogen bromide reveals four prominent methionine cleavage sites within the protein. Western blotting shows that none of the monoclonal antibody epitopes are dependent on long range interactions. Eight highly-conserved epitopes are clustered in the carboxy terminal half of the protein, while a single less-conserved epitope (for monoclonal antibody P1G12) is located at the amino terminus and appears to lie within the Gly/DMA/Phe domain."} {"id": "PMID:1283365", "title": "Distinctive distribution of HLA class II presenting and bone marrow derived cells in the anterior segment of human eyes.", "content": "Cells of bone marrow origin that normally occupy the stroma of the murine iris and ciliary body have been implicated in the immune phenomenon, anterior chamber associated immune deviation (ACAID). Following injection of antigen into the anterior chamber, cells of this type deliver an ACAID inducing signal into the systemic circulation, presumably through the outflow tract. In an effort to identify such cells in man, anterior chambers of 34 human donor eyes of different age groups were stained immunocytochemically with monoclonal antibodies directed at HLA class II molecules, CD 45 (a molecular marker of bone marrow-derived cells) and macrophage-associated membrane molecules (CD 68, CD 14). Within the outflow tissue, the cells of the filtering trabecular meshwork stained with none of those reagents. However, infrequent single, dispersed, dendritic cells were positively stained in the intertrabecular spaces. More numerous labelled cells were found in the anterior- and posterior-most portions of the non-filtering part of the trabecular meshwork. These cells were continuous with stained cells adjacent to the outer wall of Schlemm's canal and to the collector channels. Numerous labelled cells were seen in the vicinity of the intra- and episcleral vessels, the ciliary meshwork, the stroma of the ciliary muscle and epithelial processes, and the iris stroma. With advancing age, increasing numbers of CD 45+, HLA class II expressing cells appeared to accumulate in the so-called uveoscleral pathway. These results indicate that bone marrow-derived cells with the potential to function of ACAID induction reside within human eyes, and that cells of this type are located not only in the stroma of iris and ciliary body, but within the non-filtering portions of the trabecular meshwork and the uveoscleral pathway. The appearance of rare CD 45+ cells \"in transit\" in the filtering trabecular meshwork is compatible with the view that cells carrying ACAID-inducing signals to the systemic immune apparatus escape from the eye by this route.", "contents": "Distinctive distribution of HLA class II presenting and bone marrow derived cells in the anterior segment of human eyes. Cells of bone marrow origin that normally occupy the stroma of the murine iris and ciliary body have been implicated in the immune phenomenon, anterior chamber associated immune deviation (ACAID). Following injection of antigen into the anterior chamber, cells of this type deliver an ACAID inducing signal into the systemic circulation, presumably through the outflow tract. In an effort to identify such cells in man, anterior chambers of 34 human donor eyes of different age groups were stained immunocytochemically with monoclonal antibodies directed at HLA class II molecules, CD 45 (a molecular marker of bone marrow-derived cells) and macrophage-associated membrane molecules (CD 68, CD 14). Within the outflow tissue, the cells of the filtering trabecular meshwork stained with none of those reagents. However, infrequent single, dispersed, dendritic cells were positively stained in the intertrabecular spaces. More numerous labelled cells were found in the anterior- and posterior-most portions of the non-filtering part of the trabecular meshwork. These cells were continuous with stained cells adjacent to the outer wall of Schlemm's canal and to the collector channels. Numerous labelled cells were seen in the vicinity of the intra- and episcleral vessels, the ciliary meshwork, the stroma of the ciliary muscle and epithelial processes, and the iris stroma. With advancing age, increasing numbers of CD 45+, HLA class II expressing cells appeared to accumulate in the so-called uveoscleral pathway. These results indicate that bone marrow-derived cells with the potential to function of ACAID induction reside within human eyes, and that cells of this type are located not only in the stroma of iris and ciliary body, but within the non-filtering portions of the trabecular meshwork and the uveoscleral pathway. The appearance of rare CD 45+ cells \"in transit\" in the filtering trabecular meshwork is compatible with the view that cells carrying ACAID-inducing signals to the systemic immune apparatus escape from the eye by this route."} {"id": "PMID:1283369", "title": "In vitro growth and maturation of human B-cell precursors.", "content": "Purified B cell precursors (BCP) (CD10+ CD19+ surface-membrane (s)Ig-cells) isolated from human fetal bone marrow (BM) were cultured with various cytokines, in the presence or absence of a fibroblastic stromal cell layer derived from adult human BM. We demonstrated that IL-7, IL-3, and stem-cell factor (SCF) participate in inducing low magnitude BCP proliferation in the absence of stroma. Addition of either IL-4, IFN (alpha and gamma), or TGF beta, resulted in significant inhibition of proliferation. Strikingly, BCP proliferated at remarkably higher levels when cultured on BM stromal cells, and this effect was further enhanced by exogenously supplied IL-7. Proliferating cells were mostly CD20+, and included both c mu- and c mu+ cells. Furthermore, BCP proliferated in response to anti CD40 antibody presented by Fc gamma RII-transfected murine fibroblastic Ltk- cells (CD40 system) (Banchereau et al. 1991), demonstrating a functional role for CD40 in B cell ontogeny. However, this effect was shown to require a second signal, which could be specifically provided by IL-3 among a panel of cytokines examined. Finally, although suggestive of BCP maturation, the culture systems examined did not permit the transition to mature B cells (sIgM+ sIgD+).", "contents": "In vitro growth and maturation of human B-cell precursors. Purified B cell precursors (BCP) (CD10+ CD19+ surface-membrane (s)Ig-cells) isolated from human fetal bone marrow (BM) were cultured with various cytokines, in the presence or absence of a fibroblastic stromal cell layer derived from adult human BM. We demonstrated that IL-7, IL-3, and stem-cell factor (SCF) participate in inducing low magnitude BCP proliferation in the absence of stroma. Addition of either IL-4, IFN (alpha and gamma), or TGF beta, resulted in significant inhibition of proliferation. Strikingly, BCP proliferated at remarkably higher levels when cultured on BM stromal cells, and this effect was further enhanced by exogenously supplied IL-7. Proliferating cells were mostly CD20+, and included both c mu- and c mu+ cells. Furthermore, BCP proliferated in response to anti CD40 antibody presented by Fc gamma RII-transfected murine fibroblastic Ltk- cells (CD40 system) (Banchereau et al. 1991), demonstrating a functional role for CD40 in B cell ontogeny. However, this effect was shown to require a second signal, which could be specifically provided by IL-3 among a panel of cytokines examined. Finally, although suggestive of BCP maturation, the culture systems examined did not permit the transition to mature B cells (sIgM+ sIgD+)."} {"id": "PMID:1283370", "title": "Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia.", "content": "The effects of finasteride, a potent 5 alpha-reductase inhibitor, were assessed in patients with benign prostatic hyperplasia. Patients were treated with finasteride or placebo for 24 weeks in a double-blind multicenter study followed by a 12-month open-extension period. After 24 weeks, finasteride-treated patients, when compared to placebo-treated patients, showed a significant reduction in prostate volume (22.5% median decrease) and prostate significant antigen (32.4% median decrease), a significant increase in maximum urinary flow (1.6 ml/s mean increase from baseline) and a significant improvement in their obstructive symptom scores (two-point decrease from baseline). Finasteride was well tolerated, and the improvements in prostate volume, maximum urinary flow rate and obstructive symptom scores observed in the controlled study were maintained throughout the extension study.", "contents": "Scandinavian clinical study of finasteride in the treatment of benign prostatic hyperplasia. The effects of finasteride, a potent 5 alpha-reductase inhibitor, were assessed in patients with benign prostatic hyperplasia. Patients were treated with finasteride or placebo for 24 weeks in a double-blind multicenter study followed by a 12-month open-extension period. After 24 weeks, finasteride-treated patients, when compared to placebo-treated patients, showed a significant reduction in prostate volume (22.5% median decrease) and prostate significant antigen (32.4% median decrease), a significant increase in maximum urinary flow (1.6 ml/s mean increase from baseline) and a significant improvement in their obstructive symptom scores (two-point decrease from baseline). Finasteride was well tolerated, and the improvements in prostate volume, maximum urinary flow rate and obstructive symptom scores observed in the controlled study were maintained throughout the extension study."} {"id": "PMID:1283371", "title": "Treatment of benign prostatic hyperplasia causing complete urinary retention through local transurethral hyperthermia.", "content": "A new technique is described for the treatment of benign prostatic hyperplasia with local hyperthermia applied transurethrally by an electromagnetic wave generator. A series of 72 treatment sessions given to 16 patients sustaining an indwelling catheter is reported. The patients were divided into two groups. Group 1 consisted of 10 patients who received 60 treatment sessions (six 60-min sessions each with 43 degrees C during 3 weeks). In group 2 there were 6 patients who received a total of 12 treatment sessions (two 120-min sessions each with a temperature of up to 44.5 degrees C for 1 week). Five of the 10 patients from group 1 (50%) and 4 of 6 patients from group 2 (67%) were relieved of the catheter and have been able to void satisfactorily during the 7- to 14-month (mean 10.1 +/- 2.8) follow-up period. The overall success rate in this series of 16 patients was 56.3%.", "contents": "Treatment of benign prostatic hyperplasia causing complete urinary retention through local transurethral hyperthermia. A new technique is described for the treatment of benign prostatic hyperplasia with local hyperthermia applied transurethrally by an electromagnetic wave generator. A series of 72 treatment sessions given to 16 patients sustaining an indwelling catheter is reported. The patients were divided into two groups. Group 1 consisted of 10 patients who received 60 treatment sessions (six 60-min sessions each with 43 degrees C during 3 weeks). In group 2 there were 6 patients who received a total of 12 treatment sessions (two 120-min sessions each with a temperature of up to 44.5 degrees C for 1 week). Five of the 10 patients from group 1 (50%) and 4 of 6 patients from group 2 (67%) were relieved of the catheter and have been able to void satisfactorily during the 7- to 14-month (mean 10.1 +/- 2.8) follow-up period. The overall success rate in this series of 16 patients was 56.3%."} {"id": "PMID:1283372", "title": "Digital rectal examination, imaging, and systematic-sextant biopsy in identifying operable lymph node-negative prostatic carcinoma.", "content": "The value of digital rectal examination, computerized tomography, magnetic resonance imaging, prostate-specific antigen, transrectal ultrasonography, and systematic-sextant biopsy in the identification of lymph node-positive patients before radical prostatectomy was analyzed in 103 men who had pelvic lymph node dissection, CT had a sensitivity of only 7% and a specificity of 96% in detecting lymph nodes, whereas magnetic resonance imaging had a sensitivity of 50% and a specificity of 100%. To evaluate the use of tumor volume in predicting lymph node metastasis, we counted the number of positive core biopsies and compared the results with the incidence of positive lymph nodes. If fewer than 5 positive core biopsies were considered negative for predicting lymph node metastasis, the sensitivity would be 67% (12 of 18), and the specificity 94% (50 of 53). To investigate tumor volume more precisely, we measured the extent of tumor volume in every biopsy as a percentage of the total biopsy core and added the percentage for the 6 biopsies. The lowest score was 10% (10% prostatic cancer in 1 of 6 cores), the highest score 580% (4 cores with 100% each and 2 with 90% each). The score was analyzed for sensitivity and specificity in predicting lymph node metastasis. If a score of 280% was used as a cutoff point, the sensitivity was 71% (10 of 14) and the specificity 91% (52 of 57). When we include the grading system by multiplying the percentage of tumor volume with tumor grade, the difference between the lymph node-positive state and lymph node-negative state becomes even more readily apparent.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Digital rectal examination, imaging, and systematic-sextant biopsy in identifying operable lymph node-negative prostatic carcinoma. The value of digital rectal examination, computerized tomography, magnetic resonance imaging, prostate-specific antigen, transrectal ultrasonography, and systematic-sextant biopsy in the identification of lymph node-positive patients before radical prostatectomy was analyzed in 103 men who had pelvic lymph node dissection, CT had a sensitivity of only 7% and a specificity of 96% in detecting lymph nodes, whereas magnetic resonance imaging had a sensitivity of 50% and a specificity of 100%. To evaluate the use of tumor volume in predicting lymph node metastasis, we counted the number of positive core biopsies and compared the results with the incidence of positive lymph nodes. If fewer than 5 positive core biopsies were considered negative for predicting lymph node metastasis, the sensitivity would be 67% (12 of 18), and the specificity 94% (50 of 53). To investigate tumor volume more precisely, we measured the extent of tumor volume in every biopsy as a percentage of the total biopsy core and added the percentage for the 6 biopsies. The lowest score was 10% (10% prostatic cancer in 1 of 6 cores), the highest score 580% (4 cores with 100% each and 2 with 90% each). The score was analyzed for sensitivity and specificity in predicting lymph node metastasis. If a score of 280% was used as a cutoff point, the sensitivity was 71% (10 of 14) and the specificity 91% (52 of 57). When we include the grading system by multiplying the percentage of tumor volume with tumor grade, the difference between the lymph node-positive state and lymph node-negative state becomes even more readily apparent.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283373", "title": "Neurochemical effects of 5-HT1 receptor ligands in pigeons.", "content": "Pigeon cerebrospinal fluid was assayed for 5-HT (5-hydroxytryptamine) and catecholamine metabolites after systemic drug injection. The 5-HT1-like receptor agonists 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969), 1-(m-trifluoromethylphenyl)piperazine (TFMPP), and 1-(3-chlorphenyl)piperazine (mCPP) decreased levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) without altering other metabolites. 5-HIAA decreases occurred at doses of 8-OH-DPAT and RU 24969 that have anti-conflict effects in pigeons, whereas TFMPP and mCPP decreased 5-HIAA only at behaviorally disruptive doses. The novel compound 1-(2-methoxyphenyl)-1-(4-(2-phthalimido)butyl)piperazine (NAN-190), a putative 5-HT1A receptor antagonist, did not affect 5-HIAA, but attenuated the decreases produced by the agonists. NAN-190 and the alpha 1-adrenoceptor antagonist prazosin increased levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol and had additive effects when co-administered. The rank order of potency in inhibiting [3H]8-OH-DPAT binding in pigeon cerebrum was 8-OH-DPAT = RU 24969 > NAN-190 >> mCPP > TFMPP. The results support suggestions that decreased 5-HT neurotransmission underlies the anxiolytic-like effects of 5-HT1A receptor agonists in pigeons.", "contents": "Neurochemical effects of 5-HT1 receptor ligands in pigeons. Pigeon cerebrospinal fluid was assayed for 5-HT (5-hydroxytryptamine) and catecholamine metabolites after systemic drug injection. The 5-HT1-like receptor agonists 8-hydroxy-(di-n-propylamino)tetralin (8-OH-DPAT), 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole (RU 24969), 1-(m-trifluoromethylphenyl)piperazine (TFMPP), and 1-(3-chlorphenyl)piperazine (mCPP) decreased levels of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) without altering other metabolites. 5-HIAA decreases occurred at doses of 8-OH-DPAT and RU 24969 that have anti-conflict effects in pigeons, whereas TFMPP and mCPP decreased 5-HIAA only at behaviorally disruptive doses. The novel compound 1-(2-methoxyphenyl)-1-(4-(2-phthalimido)butyl)piperazine (NAN-190), a putative 5-HT1A receptor antagonist, did not affect 5-HIAA, but attenuated the decreases produced by the agonists. NAN-190 and the alpha 1-adrenoceptor antagonist prazosin increased levels of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol and had additive effects when co-administered. The rank order of potency in inhibiting [3H]8-OH-DPAT binding in pigeon cerebrum was 8-OH-DPAT = RU 24969 > NAN-190 >> mCPP > TFMPP. The results support suggestions that decreased 5-HT neurotransmission underlies the anxiolytic-like effects of 5-HT1A receptor agonists in pigeons."} {"id": "PMID:1283374", "title": "Endothelium-derived relaxing factor inhibits platelet adhesion to cultured porcine endocardial endothelium.", "content": "By using a simple platelet binding assay, we investigated whether endothelium-derived relaxing factor (EDRF) released from endocardial endothelium influences the adhesion of unstimulated platelets to these cells. Under basal conditions 8.0 +/- 0.32% of total platelets added adhered. The nitric oxide (NO) synthase inhibitor, i.e. NG-nitro L-arginine methyl ester (L-NAME), and the EDRF inhibitor haemoglobin (Hb) increased this adhesion, but another NO synthase inhibitor, NG-monomethyl L-arginine (L-NMMA), did not. The EDRF releasing agent substance P (SP) decreased adhesion, L-NMMA reversed this inhibition, whereas L-NAME and Hb did so only partially. Superoxide dismutase (SOD) caused a marked decrease in adhesion which was fully reversed by L-NMMA, L-NAME and Hb. SOD and SP together showed a cumulative effect on platelet adhesion; this inhibition was significantly reversed by all the EDRF inhibitors, although the levels of adhesion did not return to those seen under basal conditions. These results indicate that EDRF release can inhibit the adhesion of unstimulated platelets to cultured porcine endocardium and that NO synthase inhibitors have differential effects on basal and stimulated EDRF release by these cells.", "contents": "Endothelium-derived relaxing factor inhibits platelet adhesion to cultured porcine endocardial endothelium. By using a simple platelet binding assay, we investigated whether endothelium-derived relaxing factor (EDRF) released from endocardial endothelium influences the adhesion of unstimulated platelets to these cells. Under basal conditions 8.0 +/- 0.32% of total platelets added adhered. The nitric oxide (NO) synthase inhibitor, i.e. NG-nitro L-arginine methyl ester (L-NAME), and the EDRF inhibitor haemoglobin (Hb) increased this adhesion, but another NO synthase inhibitor, NG-monomethyl L-arginine (L-NMMA), did not. The EDRF releasing agent substance P (SP) decreased adhesion, L-NMMA reversed this inhibition, whereas L-NAME and Hb did so only partially. Superoxide dismutase (SOD) caused a marked decrease in adhesion which was fully reversed by L-NMMA, L-NAME and Hb. SOD and SP together showed a cumulative effect on platelet adhesion; this inhibition was significantly reversed by all the EDRF inhibitors, although the levels of adhesion did not return to those seen under basal conditions. These results indicate that EDRF release can inhibit the adhesion of unstimulated platelets to cultured porcine endocardium and that NO synthase inhibitors have differential effects on basal and stimulated EDRF release by these cells."} {"id": "PMID:1283375", "title": "Inhibition of islet nitric oxide synthase increases arginine-induced insulin release.", "content": "NG-Nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase, markedly (+50%) increased the L-arginine-induced insulin release from isolated mouse islets but did not itself influence insulin secretion. An abundance of mouse islet cells were positively stained for the enzyme NADPH diaphorase, which reportedly is a marker for NO synthase. The data suggest that the NO synthase activity in mouse islet tissue may inhibit insulin secreting processes and that L-arginine has a dual action on insulin release.", "contents": "Inhibition of islet nitric oxide synthase increases arginine-induced insulin release. NG-Nitro-L-arginine, an inhibitor of nitric oxide (NO) synthase, markedly (+50%) increased the L-arginine-induced insulin release from isolated mouse islets but did not itself influence insulin secretion. An abundance of mouse islet cells were positively stained for the enzyme NADPH diaphorase, which reportedly is a marker for NO synthase. The data suggest that the NO synthase activity in mouse islet tissue may inhibit insulin secreting processes and that L-arginine has a dual action on insulin release."} {"id": "PMID:1283377", "title": "Neurotensin, substance P, gastrin/cholecystokinin, and bombesin in the intestine of the tilapia (Oreochromis mossambicus) and the goldfish (Carassius auratus): immunochemical detection and effects on electrophysiological characteristics.", "content": "The distribution of neurotensin-, substance P-, gastrin/cholecystokinin/carerulein- and bombesin-like immunoreactivities has been studied in the gut of the tilapia (Oreochromis mossambicus) and the goldfish (Carassius auratus) using immunohistochemistry and radioimmunoassay; the electrophysiological effects of these peptides on the intestinal epithelium were also examined with the Ussing-type chamber technique. Neurotensin- and gastrin/cholecystokinin/caerulein-like immunoreactivities were present in endocrine cells in both species. Substance P- and bombesin-like immunoreactive endocrine cells were present in the intestine of the tilapia. Neurotensin-like immunoreactivity was observed in varicose fibers and nerve cell bodies in the muscle layers and myenteric plexus of both species, whereas nerve fibers showing substance P-like immunoreactivity were found in the goldfish only. Using radioimmunoassays, neurotensin- and gastrin/cholecystokinin/caerulein-like immunoreactive materials were detected in intestinal extracts of both species. The amounts of substance P- and bombesin-like material were below detection level. The ion selectivity of the intestinal epithelium of both species was modulated by exogenously applied neurotensin. This effect was blocked by tetrodotoxin in the tilapia but not in the goldfish. In the tilapia, neurotensin may act via stimulation of a cAMP-dependent increase of the Cl- conductance of the tight junctions, whereas in the goldfish, neurotensin induced, via an unknown messenger, a transient decrease of the cation selectivity without a decrease in the resistance. Substance P, cholecystokinin, and bombesin were without effect on the electrophysiological characteristics of the epithelium.", "contents": "Neurotensin, substance P, gastrin/cholecystokinin, and bombesin in the intestine of the tilapia (Oreochromis mossambicus) and the goldfish (Carassius auratus): immunochemical detection and effects on electrophysiological characteristics. The distribution of neurotensin-, substance P-, gastrin/cholecystokinin/carerulein- and bombesin-like immunoreactivities has been studied in the gut of the tilapia (Oreochromis mossambicus) and the goldfish (Carassius auratus) using immunohistochemistry and radioimmunoassay; the electrophysiological effects of these peptides on the intestinal epithelium were also examined with the Ussing-type chamber technique. Neurotensin- and gastrin/cholecystokinin/caerulein-like immunoreactivities were present in endocrine cells in both species. Substance P- and bombesin-like immunoreactive endocrine cells were present in the intestine of the tilapia. Neurotensin-like immunoreactivity was observed in varicose fibers and nerve cell bodies in the muscle layers and myenteric plexus of both species, whereas nerve fibers showing substance P-like immunoreactivity were found in the goldfish only. Using radioimmunoassays, neurotensin- and gastrin/cholecystokinin/caerulein-like immunoreactive materials were detected in intestinal extracts of both species. The amounts of substance P- and bombesin-like material were below detection level. The ion selectivity of the intestinal epithelium of both species was modulated by exogenously applied neurotensin. This effect was blocked by tetrodotoxin in the tilapia but not in the goldfish. In the tilapia, neurotensin may act via stimulation of a cAMP-dependent increase of the Cl- conductance of the tight junctions, whereas in the goldfish, neurotensin induced, via an unknown messenger, a transient decrease of the cation selectivity without a decrease in the resistance. Substance P, cholecystokinin, and bombesin were without effect on the electrophysiological characteristics of the epithelium."} {"id": "PMID:1283378", "title": "Occurrence of alginate gene sequences among members of the pseudomonad rRNA homology groups I-IV.", "content": "Total genomic DNA of 13 pseudomonads representing rRNA homology groups I-IV were screened for sequences homologous to four Pseudomonas aeruginosa alginate (alg) genes by Southern hybridization. Biotinylated probes for three structural genes (algA, algC and algD) and one regulatory gene (algR1) were prepared. Genomic DNA of strains representing group I (P. syringae pv. glycinea, P. viridiflava and P. corrugata) hybridized with all four gene probes. Hybridizing fragments were of differing sizes, indicating that evolutionary divergence among group I members has occurred. P. corrugata has not been reported to synthesize alginate. Genomic DNA from representatives of groups II-IV gave no or very weak hybridization with the probes except for algC. This study indicates that the ability to produce alginic acid as an exopolysaccharide among the pseudomonads is restricted to members of rRNA homology group I in agreement with earlier physiological studies.", "contents": "Occurrence of alginate gene sequences among members of the pseudomonad rRNA homology groups I-IV. Total genomic DNA of 13 pseudomonads representing rRNA homology groups I-IV were screened for sequences homologous to four Pseudomonas aeruginosa alginate (alg) genes by Southern hybridization. Biotinylated probes for three structural genes (algA, algC and algD) and one regulatory gene (algR1) were prepared. Genomic DNA of strains representing group I (P. syringae pv. glycinea, P. viridiflava and P. corrugata) hybridized with all four gene probes. Hybridizing fragments were of differing sizes, indicating that evolutionary divergence among group I members has occurred. P. corrugata has not been reported to synthesize alginate. Genomic DNA from representatives of groups II-IV gave no or very weak hybridization with the probes except for algC. This study indicates that the ability to produce alginic acid as an exopolysaccharide among the pseudomonads is restricted to members of rRNA homology group I in agreement with earlier physiological studies."} {"id": "PMID:1283379", "title": "Structure of a neutral glycan from the lipopolysaccharides of reference strains for Serratia marcescens serogroups O2 and O3.", "content": "Serogroups O2 and O3 of Serratia marcescens are differentiated by acidic glycans present in the aqueous phase when lipopolysaccharides are extracted from the reference strains by the aqueous-phenol method. The phenolic phases of these extracts from both strains also contain lipopolysaccharides, from which the same neutral glycan is released on milk acid hydrolysis. The neutral glycan has the disaccharide repeating-unit shown, and accounts for the cross-reactions between the two serogroups and also with serogroup O21: --> 4)-alpha-D-GlcpNAc-(1-->4)-beta-D-ManpNAc-(1--.", "contents": "Structure of a neutral glycan from the lipopolysaccharides of reference strains for Serratia marcescens serogroups O2 and O3. Serogroups O2 and O3 of Serratia marcescens are differentiated by acidic glycans present in the aqueous phase when lipopolysaccharides are extracted from the reference strains by the aqueous-phenol method. The phenolic phases of these extracts from both strains also contain lipopolysaccharides, from which the same neutral glycan is released on milk acid hydrolysis. The neutral glycan has the disaccharide repeating-unit shown, and accounts for the cross-reactions between the two serogroups and also with serogroup O21: --> 4)-alpha-D-GlcpNAc-(1-->4)-beta-D-ManpNAc-(1--."} {"id": "PMID:1283380", "title": "Atopic dermatitis and food hypersensitivity in children.", "content": "Atopic dermatitis is a common condition of early childhood. The association of atopic dermatitis and allergy has been studied for several years. Recent work has shown that food hypersensitivity does play a role as an exacerbating factor in some children with atopic dermatitis. This hypersensitivity will be limited typically to one or two food antigens. Children placed on appropriate elimination diets can be expected to have significant improvement in their clinical course.", "contents": "Atopic dermatitis and food hypersensitivity in children. Atopic dermatitis is a common condition of early childhood. The association of atopic dermatitis and allergy has been studied for several years. Recent work has shown that food hypersensitivity does play a role as an exacerbating factor in some children with atopic dermatitis. This hypersensitivity will be limited typically to one or two food antigens. Children placed on appropriate elimination diets can be expected to have significant improvement in their clinical course."} {"id": "PMID:1283383", "title": "Comparative effect of galanin and pyridostigmine on the growth hormone response to growth hormone-releasing hormone in normal aged subjects.", "content": "The aim of our study was to investigate the effects of aging on the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) alone and in combination with either the neuropeptide galanin or the acetylcholinesterase inhibitor pyridostigmine (PD) in normal subjects. In protocol 1 (GHRH/galanin), 9 old healthy volunteers, ranging in age from 68 to 97 years, and 6 young subjects, ranging in age from 25 to 31 years, received: (a) human GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) porcine galanin, 500 micrograms in 100 ml saline, as an intravenous infusion from -10 to 30 min combined with GHRH, 100 micrograms i.v. at time 0. In protocol 2 (GHRH/PD), 14 old healthy volunteers, ranging in age from 65 to 91 years, and 11 young subjects, ranging in age from 19 to 34 years, received: (a) GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) PD, 120 mg administered per os 60 min before GHRH, 100 micrograms as an intravenous bolus. Blood samples for GH were drawn at -75, -60 (time of PD administration), -45, -30, -15, -10 (time of beginning of galanin infusion), 0 (time of GHRH injection), 15, 30, 45, 60, 90, and 120 min. The GH response to GHRH was significantly (< 0.05) enhanced either by galanin or PD pretreatment both in young and old subjects. However, the GH response to GHRH alone or combined with either galanin or PD was significantly greater in the young subjects as compared to the old subjects.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Comparative effect of galanin and pyridostigmine on the growth hormone response to growth hormone-releasing hormone in normal aged subjects. The aim of our study was to investigate the effects of aging on the growth hormone (GH) response to growth hormone-releasing hormone (GHRH) alone and in combination with either the neuropeptide galanin or the acetylcholinesterase inhibitor pyridostigmine (PD) in normal subjects. In protocol 1 (GHRH/galanin), 9 old healthy volunteers, ranging in age from 68 to 97 years, and 6 young subjects, ranging in age from 25 to 31 years, received: (a) human GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) porcine galanin, 500 micrograms in 100 ml saline, as an intravenous infusion from -10 to 30 min combined with GHRH, 100 micrograms i.v. at time 0. In protocol 2 (GHRH/PD), 14 old healthy volunteers, ranging in age from 65 to 91 years, and 11 young subjects, ranging in age from 19 to 34 years, received: (a) GHRH (1-29)NH2, 100 micrograms in 1 ml saline, as an intravenous bolus, and (b) PD, 120 mg administered per os 60 min before GHRH, 100 micrograms as an intravenous bolus. Blood samples for GH were drawn at -75, -60 (time of PD administration), -45, -30, -15, -10 (time of beginning of galanin infusion), 0 (time of GHRH injection), 15, 30, 45, 60, 90, and 120 min. The GH response to GHRH was significantly (< 0.05) enhanced either by galanin or PD pretreatment both in young and old subjects. However, the GH response to GHRH alone or combined with either galanin or PD was significantly greater in the young subjects as compared to the old subjects.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283381", "title": "New World plants; New World drugs.", "content": "The \"discovery\" and eventual colonization and exploitation of the New World by Europeans created the opportunity for the development of medicines from numerous plants native to the Western Hemisphere. Many of these plants had been employed by native cultures for centuries or millenia. The plants and, eventually, isolated drugs derived from them were incorporated into the materia media of the Europeans both in Europe and in the new colonies. Many became official in the United States Pharmacopeia (USP); a few still remain today. In all, 30 plants and/or their derivatives are briefly profiled. The subjects of plant-based medicines is becoming more timely as millions of Europeans and Americans begin to seek \"natural\" remedies for self-medication. Unfortunately, lack of patentability and high new-drug approval costs keep many traditional plant medicines from obtaining proper recognition.", "contents": "New World plants; New World drugs. The \"discovery\" and eventual colonization and exploitation of the New World by Europeans created the opportunity for the development of medicines from numerous plants native to the Western Hemisphere. Many of these plants had been employed by native cultures for centuries or millenia. The plants and, eventually, isolated drugs derived from them were incorporated into the materia media of the Europeans both in Europe and in the new colonies. Many became official in the United States Pharmacopeia (USP); a few still remain today. In all, 30 plants and/or their derivatives are briefly profiled. The subjects of plant-based medicines is becoming more timely as millions of Europeans and Americans begin to seek \"natural\" remedies for self-medication. Unfortunately, lack of patentability and high new-drug approval costs keep many traditional plant medicines from obtaining proper recognition."} {"id": "PMID:1283384", "title": "Endogenous interferon plasma levels and antipyrine pharmacokinetics in patients with viral infections.", "content": "We investigated the pharmacokinetics of antipyrine and the endogenous plasma levels of interferon alpha (IFN alpha), interferon beta (IFN beta) and interferon gamma (IFN gamma) in 10 otherwise healthy volunteers before outbreak (baseline) and in the symptomatic interval of an acute viral respiratory infection, and also in HIV-1 infected homosexual patients in stadium WR 2-3 (n = 11) and WR 5-6 (n = 11) before and one day after application of the antiretroviral agent zidovudine 800 mg day-1 for 14 days. Interferons were measured by RIA or ELISA, respectively. The concentrations of antipyrine and its metabolites in serum and urine were measured by HPLC. Antipyrine is a pharmacokinetic model substance to estimate the cytochrome P 450 enzyme activity. The plasma levels of IFN alpha and IFN gamma in the symptomatic interval of an acute viral respiratory infection were elevated from 4.7 U ml-1 to 12.6 U ml-1 and from 0.3 U ml-1 to 3.4 U ml-1, respectively. The antipyrine clearance showed a significant decrease from 57.9 ml min-1 to 45.0 ml min-1. In the HIV-1 infected patients in stadium WR 2-3 no alterations in plasma levels of interferons or in the pharmacokinetics of antipyrine were observed after treatment with zidovudine. In contrast to these results, in patients in stadium WR 5-6 we found a significant decrease of IFN alpha and an elevation of the clearance and the clearances to metabolite of antipyrine by about 20 percent.", "contents": "Endogenous interferon plasma levels and antipyrine pharmacokinetics in patients with viral infections. We investigated the pharmacokinetics of antipyrine and the endogenous plasma levels of interferon alpha (IFN alpha), interferon beta (IFN beta) and interferon gamma (IFN gamma) in 10 otherwise healthy volunteers before outbreak (baseline) and in the symptomatic interval of an acute viral respiratory infection, and also in HIV-1 infected homosexual patients in stadium WR 2-3 (n = 11) and WR 5-6 (n = 11) before and one day after application of the antiretroviral agent zidovudine 800 mg day-1 for 14 days. Interferons were measured by RIA or ELISA, respectively. The concentrations of antipyrine and its metabolites in serum and urine were measured by HPLC. Antipyrine is a pharmacokinetic model substance to estimate the cytochrome P 450 enzyme activity. The plasma levels of IFN alpha and IFN gamma in the symptomatic interval of an acute viral respiratory infection were elevated from 4.7 U ml-1 to 12.6 U ml-1 and from 0.3 U ml-1 to 3.4 U ml-1, respectively. The antipyrine clearance showed a significant decrease from 57.9 ml min-1 to 45.0 ml min-1. In the HIV-1 infected patients in stadium WR 2-3 no alterations in plasma levels of interferons or in the pharmacokinetics of antipyrine were observed after treatment with zidovudine. In contrast to these results, in patients in stadium WR 5-6 we found a significant decrease of IFN alpha and an elevation of the clearance and the clearances to metabolite of antipyrine by about 20 percent."} {"id": "PMID:1283382", "title": "European animal diseases brought to the New World.", "content": "Beginning with Columbus' second voyage to the New World in 1493, domesticated animals have been imported to establish herds and flocks for the development of animal agriculture and as mounts for the early explorers. Some of these imports harbored agents of disease that were transmitted to healthy animals during their ocean voyage or to their offspring born in the New World. Some of these diseases were eradicated, others have persisted to the present.", "contents": "European animal diseases brought to the New World. Beginning with Columbus' second voyage to the New World in 1493, domesticated animals have been imported to establish herds and flocks for the development of animal agriculture and as mounts for the early explorers. Some of these imports harbored agents of disease that were transmitted to healthy animals during their ocean voyage or to their offspring born in the New World. Some of these diseases were eradicated, others have persisted to the present."} {"id": "PMID:1283385", "title": "The effect of the new immunosuppressive drug FK506 on the formation of secondary metabolites of cyclosporin A.", "content": "Interactions of FK506 with the cyclosporin A (CsA) metabolism are described. These interactions were not differentiated between the primary and secondary part of metabolism. The combination-therapy with cyclosporin A and diltiazem has shown, that not only the blood levels of CsA were increased, but also the blood levels of the primary CsA-metabolite M17. In the presented in in-vitro-investigations 1.7 microM tritium-labelled CsA was incubated for 90 min with human liver microsomes. The inhibitory effect of FK506 (6 microM) was observed with coincubation under the same conditions. The metabolites were quantified by detection of radioactivity of the elution-fractions after HPLC. The results showed strong inhibition on the formation of both, the primary and secondary CsA-metabolites by FK506. With the same concentration diltiazem and erythromycin exhibited only an inhibition of the formation of secondary CsA-metabolites. In clinical investigations with FK506 in combination with CsA it is necessary to control blood levels of CsA and also its primary metabolites.", "contents": "The effect of the new immunosuppressive drug FK506 on the formation of secondary metabolites of cyclosporin A. Interactions of FK506 with the cyclosporin A (CsA) metabolism are described. These interactions were not differentiated between the primary and secondary part of metabolism. The combination-therapy with cyclosporin A and diltiazem has shown, that not only the blood levels of CsA were increased, but also the blood levels of the primary CsA-metabolite M17. In the presented in in-vitro-investigations 1.7 microM tritium-labelled CsA was incubated for 90 min with human liver microsomes. The inhibitory effect of FK506 (6 microM) was observed with coincubation under the same conditions. The metabolites were quantified by detection of radioactivity of the elution-fractions after HPLC. The results showed strong inhibition on the formation of both, the primary and secondary CsA-metabolites by FK506. With the same concentration diltiazem and erythromycin exhibited only an inhibition of the formation of secondary CsA-metabolites. In clinical investigations with FK506 in combination with CsA it is necessary to control blood levels of CsA and also its primary metabolites."} {"id": "PMID:1283386", "title": "Calcium localization in the shell-forming tissue of the freshwater snail, Biomphalaria glabrata: a comparative study of various methods for localizing calcium.", "content": "The routes calcium might take across the mantle to the shell have been investigated with various electron-microscopical techniques in the freshwater snail Biomphalaria glabrata (Planorbidae, Basommatophora). In chemically-fixed tissue, calcium was precipitated with a tannic acid-antimonate technique in predominantly the intercellular spaces of the outer mantle epithelium and the interstitium below it. Some vacuoles of the outer mantle epithelium and one type of mucus cell in the inner mantle epithelium also contained precipitate. The presence of calcium in the precipitates was proved by electron energy loss spectroscopy combined with electron spectroscopic imaging. Incubation with lead acetate and uranyl acetate revealed binding-sites for calcium in the intercellular spaces of the epithelia interstitium and the mucus cells of the inner mantle epithelium. Precipitates were also seen after all incubations in the calcium spherites of the connective tissue. The concentrations of calcium and other elements were analysed in freeze-dried ultrathin sections of cryofixed mantle tissue by means of energy-dispersive X-ray microanalysis. Only in mitochondria of the musculature could high amounts of calcium and phosphorous be detected.", "contents": "Calcium localization in the shell-forming tissue of the freshwater snail, Biomphalaria glabrata: a comparative study of various methods for localizing calcium. The routes calcium might take across the mantle to the shell have been investigated with various electron-microscopical techniques in the freshwater snail Biomphalaria glabrata (Planorbidae, Basommatophora). In chemically-fixed tissue, calcium was precipitated with a tannic acid-antimonate technique in predominantly the intercellular spaces of the outer mantle epithelium and the interstitium below it. Some vacuoles of the outer mantle epithelium and one type of mucus cell in the inner mantle epithelium also contained precipitate. The presence of calcium in the precipitates was proved by electron energy loss spectroscopy combined with electron spectroscopic imaging. Incubation with lead acetate and uranyl acetate revealed binding-sites for calcium in the intercellular spaces of the epithelia interstitium and the mucus cells of the inner mantle epithelium. Precipitates were also seen after all incubations in the calcium spherites of the connective tissue. The concentrations of calcium and other elements were analysed in freeze-dried ultrathin sections of cryofixed mantle tissue by means of energy-dispersive X-ray microanalysis. Only in mitochondria of the musculature could high amounts of calcium and phosphorous be detected."} {"id": "PMID:1283387", "title": "Relationship between interphase AgNOR distribution and nucleolar size in cancer cells.", "content": "We have studied the relationship between interphase nucleolar organizer region (NOR) distribution and nucleolar size in cancer cells at light-microscopical level. Thirteen cases of formalin-fixed bladder cancer and fifteen cases of methacarn-fixed tumours of different origin were used. Nucleoli of the former cases were stained by Phloxine B and of the latter by Toluidine Blue. Selective visualization of interphase NORs was obtained by carrying out the one-step silver staining reaction for AgNOR proteins (Ploton et al., 1986). The area occupied by Phloxine B- or Toluidine Blue-stained nucleoli and interphase silver-stained NORs was measured by means of an automated image analyser. Both in bladder cancers and in the other tumour lesions nucleolar and interphase AgNOR areas were linearly related (r = 0.95 and r = 0.96, respectively, P < 0.001). The close relationship between the area of nucleoli and that of silver-stained nucleolar structures was maintained even if the silver-staining procedure was prolonged beyond the optimal time length for selective interphase NOR staining. In the latter case, however, single interphase AgNORs were no longer visible within the nucleolar body which was, in fact, homogeneously stained. These data indicate that evaluation of the interphase AgNOR area has the same relevance, in tumour pathology, as whole nucleolar size measurement.", "contents": "Relationship between interphase AgNOR distribution and nucleolar size in cancer cells. We have studied the relationship between interphase nucleolar organizer region (NOR) distribution and nucleolar size in cancer cells at light-microscopical level. Thirteen cases of formalin-fixed bladder cancer and fifteen cases of methacarn-fixed tumours of different origin were used. Nucleoli of the former cases were stained by Phloxine B and of the latter by Toluidine Blue. Selective visualization of interphase NORs was obtained by carrying out the one-step silver staining reaction for AgNOR proteins (Ploton et al., 1986). The area occupied by Phloxine B- or Toluidine Blue-stained nucleoli and interphase silver-stained NORs was measured by means of an automated image analyser. Both in bladder cancers and in the other tumour lesions nucleolar and interphase AgNOR areas were linearly related (r = 0.95 and r = 0.96, respectively, P < 0.001). The close relationship between the area of nucleoli and that of silver-stained nucleolar structures was maintained even if the silver-staining procedure was prolonged beyond the optimal time length for selective interphase NOR staining. In the latter case, however, single interphase AgNORs were no longer visible within the nucleolar body which was, in fact, homogeneously stained. These data indicate that evaluation of the interphase AgNOR area has the same relevance, in tumour pathology, as whole nucleolar size measurement."} {"id": "PMID:1283388", "title": "Inhibitory effects of organotin compounds on histamine release from rat serosal mast cells.", "content": "Tributyltin inhibited compound 48/80-induced histamine release from rat serosal mast cells in a dose-related manner. Triphenyltin and tripropyltin also showed a strong inhibitory effect on the histamine release and the degree of the inhibition was the same as that of tributyltin. The inhibitory effects of other organometals were much smaller than those of the organotins. Tributyltin and triphenyltin also showed a tendency to inhibit histamine release induced by concanavalin A + phosphatidylserine and calcium ionophore A 23187. The present results suggest that certain triorganotin compounds may have a specific inhibitory effect on histamine release by acting on the same process in each of the three stimulus responses.", "contents": "Inhibitory effects of organotin compounds on histamine release from rat serosal mast cells. Tributyltin inhibited compound 48/80-induced histamine release from rat serosal mast cells in a dose-related manner. Triphenyltin and tripropyltin also showed a strong inhibitory effect on the histamine release and the degree of the inhibition was the same as that of tributyltin. The inhibitory effects of other organometals were much smaller than those of the organotins. Tributyltin and triphenyltin also showed a tendency to inhibit histamine release induced by concanavalin A + phosphatidylserine and calcium ionophore A 23187. The present results suggest that certain triorganotin compounds may have a specific inhibitory effect on histamine release by acting on the same process in each of the three stimulus responses."} {"id": "PMID:1283390", "title": "Effect of polysaccharide interactions on antibiotic susceptibility of Pseudomonas aeruginosa.", "content": "The relative viscosity of Pseudomonas aeruginosa alginate was shown to increase markedly when combined with mucin, Ca2+ ions and the exopolysaccharide from Pseudomonas cepacia. The presence of such a heterodisperse polysaccharide solution significantly reduced the diffusion and hence antimicrobial activity of tobramycin and to a lesser extent ciprofloxacin against Ps. aeruginosa by factors of 90 and 2.5-fold respectively over a 5 h incubation period. The clinical implications of these results are discussed in relation to cystic fibrosis.", "contents": "Effect of polysaccharide interactions on antibiotic susceptibility of Pseudomonas aeruginosa. The relative viscosity of Pseudomonas aeruginosa alginate was shown to increase markedly when combined with mucin, Ca2+ ions and the exopolysaccharide from Pseudomonas cepacia. The presence of such a heterodisperse polysaccharide solution significantly reduced the diffusion and hence antimicrobial activity of tobramycin and to a lesser extent ciprofloxacin against Ps. aeruginosa by factors of 90 and 2.5-fold respectively over a 5 h incubation period. The clinical implications of these results are discussed in relation to cystic fibrosis."} {"id": "PMID:1283392", "title": "Preparation and properties of monoclonal antibodies against lipopolysaccharide-sensitive serine protease zymogen, factor C, from horseshoe crab (Tachypleus tridentatus) hemocytes.", "content": "Seventeen murine monoclonal antibodies (mAbs) against horseshoe crab clotting factor, factor C, were prepared and characterized. When the binding sites of these mAbs were analyzed by immunoblotting, ten mAbs recognized nonreduced factor C, five mAbs were directed against the heavy chain, and two mAbs were directed against the B chain. Three mAbs, 1H4, 2C12, and 2A7, one selected from each group, were used for further study. The mAb 1H4, which recognized only nonreduced factor C molecule, inhibited the factor C activity in a dose-dependent manner. It also inhibited lipopolysaccharide (LPS)- and alpha-chymotrypsin-mediated activations of the zymogen factor C, suggesting that 1H4 binds close to the active site and/or the substrate-binding site located in the serine protease domain (B chain) of factor C. On the other hand, 2C12 and 2A7 recognized, respectively, an epitope located in the heavy and the B chains, and inhibited LPS-mediated activation of factor C, but not alpha-chymotrypsin-mediated activation of factor C or factor C activity. Both F(ab')2 and Fab' fragments derived from 2C12 inhibited LPS-mediated activation in the same manner. These three mAbs did not bind with LPS, although a factor C-mAb complex was able to bind LPS, suggesting that the LPS-mediated activation of the zymogen factor C was induced through intermolecular interaction between the LPS-bound factor C molecules. The dissociation constants (Kd) for 1H4, 2C12, and 2A7 binding to factor C were determined as 1.9 x 10(-9), 0.6 x 10(-10), and 1.8 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Preparation and properties of monoclonal antibodies against lipopolysaccharide-sensitive serine protease zymogen, factor C, from horseshoe crab (Tachypleus tridentatus) hemocytes. Seventeen murine monoclonal antibodies (mAbs) against horseshoe crab clotting factor, factor C, were prepared and characterized. When the binding sites of these mAbs were analyzed by immunoblotting, ten mAbs recognized nonreduced factor C, five mAbs were directed against the heavy chain, and two mAbs were directed against the B chain. Three mAbs, 1H4, 2C12, and 2A7, one selected from each group, were used for further study. The mAb 1H4, which recognized only nonreduced factor C molecule, inhibited the factor C activity in a dose-dependent manner. It also inhibited lipopolysaccharide (LPS)- and alpha-chymotrypsin-mediated activations of the zymogen factor C, suggesting that 1H4 binds close to the active site and/or the substrate-binding site located in the serine protease domain (B chain) of factor C. On the other hand, 2C12 and 2A7 recognized, respectively, an epitope located in the heavy and the B chains, and inhibited LPS-mediated activation of factor C, but not alpha-chymotrypsin-mediated activation of factor C or factor C activity. Both F(ab')2 and Fab' fragments derived from 2C12 inhibited LPS-mediated activation in the same manner. These three mAbs did not bind with LPS, although a factor C-mAb complex was able to bind LPS, suggesting that the LPS-mediated activation of the zymogen factor C was induced through intermolecular interaction between the LPS-bound factor C molecules. The dissociation constants (Kd) for 1H4, 2C12, and 2A7 binding to factor C were determined as 1.9 x 10(-9), 0.6 x 10(-10), and 1.8 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283393", "title": "Engineering of artificial cell adhesion proteins by grafting the Arg-Gly-Asp cell adhesive signal to a calpastatin segment.", "content": "A new artificial cell adhesive protein was engineered by grafting the Arg-Gly-Asp (RGD) sequence, the minimal recognition signal of fibronectin for interaction with integrins, to a calpastatin segment by in vitro mutagenesis. The mutagenized protein showed cell adhesive activity in addition to calpain inhibitory activity. The RGD signal grafted to the calpastatin segment was recognized by the vitronectin receptor but not by the fibronectin receptor.", "contents": "Engineering of artificial cell adhesion proteins by grafting the Arg-Gly-Asp cell adhesive signal to a calpastatin segment. A new artificial cell adhesive protein was engineered by grafting the Arg-Gly-Asp (RGD) sequence, the minimal recognition signal of fibronectin for interaction with integrins, to a calpastatin segment by in vitro mutagenesis. The mutagenized protein showed cell adhesive activity in addition to calpain inhibitory activity. The RGD signal grafted to the calpastatin segment was recognized by the vitronectin receptor but not by the fibronectin receptor."} {"id": "PMID:1283394", "title": "Microbore liquid chromatography with dual electrochemical detection for the determination of serotonin and 5-hydroxyindoleacetic acid in rat brain dialysates.", "content": "A microbore liquid chromatographic assay with dual electrochemical detection is described for the determination of serotonin and its metabolite 5-hydroxyindoleacetic acid in rat brain dialysates. The concentration of serotonin in these samples is usually in the low nanomolar range (fmol per 20 microliters range). To optimize separation and detection, several adaptations were made to the system with respect to the injection valve, flow-rate of the pump, connections between injector, column and detector, and cell volume of the detector. These aspects are discussed, as well as the procedure developed for optimal peak identification of serotonin and correct estimation of 5-hydroxyindoleacetic acid. The assay allows the measurement of basal serotonin release without the use of a re-uptake inhibitor added to the perfusion fluid.", "contents": "Microbore liquid chromatography with dual electrochemical detection for the determination of serotonin and 5-hydroxyindoleacetic acid in rat brain dialysates. A microbore liquid chromatographic assay with dual electrochemical detection is described for the determination of serotonin and its metabolite 5-hydroxyindoleacetic acid in rat brain dialysates. The concentration of serotonin in these samples is usually in the low nanomolar range (fmol per 20 microliters range). To optimize separation and detection, several adaptations were made to the system with respect to the injection valve, flow-rate of the pump, connections between injector, column and detector, and cell volume of the detector. These aspects are discussed, as well as the procedure developed for optimal peak identification of serotonin and correct estimation of 5-hydroxyindoleacetic acid. The assay allows the measurement of basal serotonin release without the use of a re-uptake inhibitor added to the perfusion fluid."} {"id": "PMID:1283395", "title": "Ultrastructure of sarcoballs on the surface of skinned amphibian skeletal muscle fibres.", "content": "The formation of sarcoballs on the surface of skinned fibres from semitendinosus muscles of Xenopus laevis, and the sarcoplasmic reticulum content of the structures, have been studied using conventional electron microscopic techniques and immunoelectron microscopy. Examination of the fibres showed many membrane-bound blebs projecting from the surface in areas where vesicles of internal membranes (including sarcoplasmic reticulum, T-tubules and mitochondria) were clustered in interfilament spaces. The blebs varied in size from 1 micron to 150 microns and those with diameters > 10 microns are referred to as sarcoballs. Small blebs were often seen in close association with each other and might have fused during sarcoball formation. The interior of the sarcoball was filled with foam-like material made up of vesicles with diameters of 100 nm to 1.0 microns. The sarcoplasmic reticulum membrane content of the sarcoballs was evaluated using two monoclonal antibodies, one to the Ca2+ ATPase of the sarcoplasmic reticulum and the second to ryanodine receptor calcium release channels in the junctional-face membrane. The antibodies bound to some components of the surface and interior of the sarcoball, but not to mitochondrial-like structures and tubular vesicles. The results show that a large component of the sarcoball and its surface is derived from sarcoplasmic reticulum and suggest that mitochondria and T-tubules might also contribute membranes to the structures. Our hypothesis is that (a) blebs bud out from the surface of the skinned fibre following fusion of internal vesicles that are extruded along interfilament channels during unrestrained contractures, (b) blebs grow into sarcoballs by additional fusion of internal membrane vesicles and fusion of adjacent blebs, and (c) the sarcoball is a foam-like structure composed of bathing medium and membrane lipid (containing membrane proteins).", "contents": "Ultrastructure of sarcoballs on the surface of skinned amphibian skeletal muscle fibres. The formation of sarcoballs on the surface of skinned fibres from semitendinosus muscles of Xenopus laevis, and the sarcoplasmic reticulum content of the structures, have been studied using conventional electron microscopic techniques and immunoelectron microscopy. Examination of the fibres showed many membrane-bound blebs projecting from the surface in areas where vesicles of internal membranes (including sarcoplasmic reticulum, T-tubules and mitochondria) were clustered in interfilament spaces. The blebs varied in size from 1 micron to 150 microns and those with diameters > 10 microns are referred to as sarcoballs. Small blebs were often seen in close association with each other and might have fused during sarcoball formation. The interior of the sarcoball was filled with foam-like material made up of vesicles with diameters of 100 nm to 1.0 microns. The sarcoplasmic reticulum membrane content of the sarcoballs was evaluated using two monoclonal antibodies, one to the Ca2+ ATPase of the sarcoplasmic reticulum and the second to ryanodine receptor calcium release channels in the junctional-face membrane. The antibodies bound to some components of the surface and interior of the sarcoball, but not to mitochondrial-like structures and tubular vesicles. The results show that a large component of the sarcoball and its surface is derived from sarcoplasmic reticulum and suggest that mitochondria and T-tubules might also contribute membranes to the structures. Our hypothesis is that (a) blebs bud out from the surface of the skinned fibre following fusion of internal vesicles that are extruded along interfilament channels during unrestrained contractures, (b) blebs grow into sarcoballs by additional fusion of internal membrane vesicles and fusion of adjacent blebs, and (c) the sarcoball is a foam-like structure composed of bathing medium and membrane lipid (containing membrane proteins)."} {"id": "PMID:1283396", "title": "The clinical expression in anticentromere antibody-positive patients is not specified by the epitope recognition of CENP-B antigen.", "content": "Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often with scleroderma). From our previous analysis of the reactivity of anticentromere sera, four independent epitopes were identified on recombinant CENP-B. The anticentromere sera displayed heterogeneity in their patterns of reactivity to the four epitopes. We have investigated to what extent this heterogeneity of the target autoepitope on CENP-B accounts for the clinical diversity of anticentromere antibody (ACA)-positive patients. A major autoepitope, epitope I, was recognized by all 40 ACA-positive sera; however, the other three epitopes were recognized differently from case to case. We could not find any significant correlation between the reactivity to CENP-B autoepitopes and the clinical presentation of ACA-positive patients. There was considerable clinical diversity, even among the nine patients showing specificity for the single major autoepitope. In conclusion, we found that, although ACA-positive patients were both clinically and immunologically heterogeneous, in most respects the clinical expression appeared to be independent of the reactivity to the CENP-B autoepitope, a finding which suggests that identification of the target epitope of CENP-B is unlikely to assist in the clinical classification of the disease in ACA-positive patients. The identification of multiple B cell epitopes on CENP-B is consistent with the concept that the self-antigen drives the antibody response. However, factors other than CENP-B autoepitope specificity must determine the clinical expression of ACA responses.", "contents": "The clinical expression in anticentromere antibody-positive patients is not specified by the epitope recognition of CENP-B antigen. Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often with scleroderma). From our previous analysis of the reactivity of anticentromere sera, four independent epitopes were identified on recombinant CENP-B. The anticentromere sera displayed heterogeneity in their patterns of reactivity to the four epitopes. We have investigated to what extent this heterogeneity of the target autoepitope on CENP-B accounts for the clinical diversity of anticentromere antibody (ACA)-positive patients. A major autoepitope, epitope I, was recognized by all 40 ACA-positive sera; however, the other three epitopes were recognized differently from case to case. We could not find any significant correlation between the reactivity to CENP-B autoepitopes and the clinical presentation of ACA-positive patients. There was considerable clinical diversity, even among the nine patients showing specificity for the single major autoepitope. In conclusion, we found that, although ACA-positive patients were both clinically and immunologically heterogeneous, in most respects the clinical expression appeared to be independent of the reactivity to the CENP-B autoepitope, a finding which suggests that identification of the target epitope of CENP-B is unlikely to assist in the clinical classification of the disease in ACA-positive patients. The identification of multiple B cell epitopes on CENP-B is consistent with the concept that the self-antigen drives the antibody response. However, factors other than CENP-B autoepitope specificity must determine the clinical expression of ACA responses."} {"id": "PMID:1283397", "title": "[Fetal growth retardation: prevention. Review of the literature].", "content": "The principle underlying preventive treatment of fetal intrauterine growth retardation can only be considered after defining various groups that are at risk and early screening based on the obstetric history, biological tests, and recently using flow rates with Doppler techniques. The use of aspirin in preventive treatment of growth retardation originates in the pharmacological properties of its molecule which allow the re-establishment of a balance of the prostoglandins. Numerous authors have studied clinical effects, its harmlessness as well as the true indications for its use. As there have been no control studies the theoretical possibilities of using Beta-Mimetic drugs has not been tested. The use of ultrasound has made it possible to try to see whether there is an improvement in the fetal state of well-being when oxygen therapy is used by the mother as it is in certain extremes to see what effect it has on placental function. Its use as an effective prophylactic has not yet been demonstrated. Promising lines of research could be assessing the effects of immunological treatments that have already been suggested (especially gammaglobulin transfusions). They have been used prophylactically with success but the series are small for well defined immunological indications.", "contents": "[Fetal growth retardation: prevention. Review of the literature]. The principle underlying preventive treatment of fetal intrauterine growth retardation can only be considered after defining various groups that are at risk and early screening based on the obstetric history, biological tests, and recently using flow rates with Doppler techniques. The use of aspirin in preventive treatment of growth retardation originates in the pharmacological properties of its molecule which allow the re-establishment of a balance of the prostoglandins. Numerous authors have studied clinical effects, its harmlessness as well as the true indications for its use. As there have been no control studies the theoretical possibilities of using Beta-Mimetic drugs has not been tested. The use of ultrasound has made it possible to try to see whether there is an improvement in the fetal state of well-being when oxygen therapy is used by the mother as it is in certain extremes to see what effect it has on placental function. Its use as an effective prophylactic has not yet been demonstrated. Promising lines of research could be assessing the effects of immunological treatments that have already been suggested (especially gammaglobulin transfusions). They have been used prophylactically with success but the series are small for well defined immunological indications."} {"id": "PMID:1283398", "title": "Assessment of airborne bacterial contamination of clean wounds: results in a tissue model.", "content": "Ovine skeletal muscle was used as a model wound and inoculated with airborne bacteria collected from a busy communal room. A specialized counting technique involving agar overlay and post-incubation tetrazolium staining was developed to allow accurate counting of small numbers of bacteria on the surfaces of muscle and membrane filters coated with substantial quantities of muscle and fat debris. Two techniques of recovering the inoculated airborne bacteria from the model wound were compared. Pulsed jet lavage with membrane filtration of the recovered fluid showed substantially better recovery, less variability and correlated more closely with controls than a tetrazolium stained 5 microns membrane filter imprint technique. Pulsed jet lavage with membrane filtration is likely to be the more appropriate technique in the assessment of contamination of wounds created in ultraclean air.", "contents": "Assessment of airborne bacterial contamination of clean wounds: results in a tissue model. Ovine skeletal muscle was used as a model wound and inoculated with airborne bacteria collected from a busy communal room. A specialized counting technique involving agar overlay and post-incubation tetrazolium staining was developed to allow accurate counting of small numbers of bacteria on the surfaces of muscle and membrane filters coated with substantial quantities of muscle and fat debris. Two techniques of recovering the inoculated airborne bacteria from the model wound were compared. Pulsed jet lavage with membrane filtration of the recovered fluid showed substantially better recovery, less variability and correlated more closely with controls than a tetrazolium stained 5 microns membrane filter imprint technique. Pulsed jet lavage with membrane filtration is likely to be the more appropriate technique in the assessment of contamination of wounds created in ultraclean air."} {"id": "PMID:1283399", "title": "Ki-67 antibody immunostaining in benign and malignant human prostatic disease.", "content": "Indices of mitotic potential may improve prognostic discrimination in patients with malignant disease. Ki-67 is a monoclonal antibody directed against an unknown proliferation antigen which has been shown to be a measure of mitotic potential. Sixty-four benign and eighty malignant prostatic biopsies were stained with the Ki-67 antibody. Nuclear and cytoplasmic staining was identified in benign and malignant biopsies using immunoalkaline phosphatase and immunoperoxidase staining reactions. Nuclear staining was identified in 14 benign and 44 malignant biopsies. Nuclear staining for Ki-67 was seen in 36% of biopsies with Gleason histological score (GHS) 2-4, 71% with GHS 5-7 and 62% with GHS 8-10. Nuclear staining was associated with advanced local disease stage, but not with metastatic disease stage. Clinical follow-up is required to establish the value of Ki-67 immunostaining as a prognostic determinant in prostatic cancer.", "contents": "Ki-67 antibody immunostaining in benign and malignant human prostatic disease. Indices of mitotic potential may improve prognostic discrimination in patients with malignant disease. Ki-67 is a monoclonal antibody directed against an unknown proliferation antigen which has been shown to be a measure of mitotic potential. Sixty-four benign and eighty malignant prostatic biopsies were stained with the Ki-67 antibody. Nuclear and cytoplasmic staining was identified in benign and malignant biopsies using immunoalkaline phosphatase and immunoperoxidase staining reactions. Nuclear staining was identified in 14 benign and 44 malignant biopsies. Nuclear staining for Ki-67 was seen in 36% of biopsies with Gleason histological score (GHS) 2-4, 71% with GHS 5-7 and 62% with GHS 8-10. Nuclear staining was associated with advanced local disease stage, but not with metastatic disease stage. Clinical follow-up is required to establish the value of Ki-67 immunostaining as a prognostic determinant in prostatic cancer."} {"id": "PMID:1283402", "title": "Complex modulation of cation channels in the tonoplast and plasma membrane of Saccharomyces cerevisiae: single-channel studies.", "content": "Detailed patch-clamp studies have been made of ion channels in the plasma membrane and tonoplast of the yeast Saccharomyces cerevisiae. The predominant tonoplast channel is a high-conductance cation-selective inward rectifier (passing ions easily into the cytoplasm from the vacuole), with its open probability (Po) peaking at about -80 mV (cytoplasm negative) and falling to near zero at +80 mV. It has a maximal slope conductance of approximately 150 pS in 100 mmol l-1 KCl, and conducts Na+, K+ and Ca2+. Elevated cytoplasmic Ca2+ concentration, alkaline pH and reducing agents can activate the channel, its likely physiological function being to adjust cytoplasmic Ca2+ concentration from the vacuolar reservoir. The predominant plasma-membrane channel is a strongly outward rectifying K+ channel (passing K+ easily out of the cytoplasm to the extracellular medium), which is activated by positive-going membrane voltages as well as by elevated cytoplasmic Ca2+ concentration and alkaline pH. Interaction between membrane voltage and [Ca2+]cyt is complex and defines three parallel closed states for the channel: a Ca(2+)-independent brief closure (I), a calcium-inhibited long closure (G) and, at large positive voltages, a calcium-induced brief blockade (B). This channel is likely to function in steady-state turgor regulation and in charge balancing during proton-coupled substrate uptake.", "contents": "Complex modulation of cation channels in the tonoplast and plasma membrane of Saccharomyces cerevisiae: single-channel studies. Detailed patch-clamp studies have been made of ion channels in the plasma membrane and tonoplast of the yeast Saccharomyces cerevisiae. The predominant tonoplast channel is a high-conductance cation-selective inward rectifier (passing ions easily into the cytoplasm from the vacuole), with its open probability (Po) peaking at about -80 mV (cytoplasm negative) and falling to near zero at +80 mV. It has a maximal slope conductance of approximately 150 pS in 100 mmol l-1 KCl, and conducts Na+, K+ and Ca2+. Elevated cytoplasmic Ca2+ concentration, alkaline pH and reducing agents can activate the channel, its likely physiological function being to adjust cytoplasmic Ca2+ concentration from the vacuolar reservoir. The predominant plasma-membrane channel is a strongly outward rectifying K+ channel (passing K+ easily out of the cytoplasm to the extracellular medium), which is activated by positive-going membrane voltages as well as by elevated cytoplasmic Ca2+ concentration and alkaline pH. Interaction between membrane voltage and [Ca2+]cyt is complex and defines three parallel closed states for the channel: a Ca(2+)-independent brief closure (I), a calcium-inhibited long closure (G) and, at large positive voltages, a calcium-induced brief blockade (B). This channel is likely to function in steady-state turgor regulation and in charge balancing during proton-coupled substrate uptake."} {"id": "PMID:1283403", "title": "Therapy of Morbus Parkinson and radical-induced neurotoxicity in the rat--in vivo voltammetric studies.", "content": "In vivo pulse voltammetry was used to study the effect of anti-parkinsonian drugs and of neurotoxins in rat striatum. It could be demonstrated that besides the well-known changes of total dopamine (DA) concentrations the applied drugs affected also the extraneuronal DA metabolism in the living rat. In addition, neurotoxin-treated rats can be used as a model to study some aspects of the Parkinson syndrome.", "contents": "Therapy of Morbus Parkinson and radical-induced neurotoxicity in the rat--in vivo voltammetric studies. In vivo pulse voltammetry was used to study the effect of anti-parkinsonian drugs and of neurotoxins in rat striatum. It could be demonstrated that besides the well-known changes of total dopamine (DA) concentrations the applied drugs affected also the extraneuronal DA metabolism in the living rat. In addition, neurotoxin-treated rats can be used as a model to study some aspects of the Parkinson syndrome."} {"id": "PMID:1283404", "title": "Blockade of ionotropic quisqualate receptor desensitization by wheat germ agglutinin in cultured postnatal rat hippocampal neurons.", "content": "1. The effects of the lectin wheat germ agglutinin (WGA) on quisqualate-gated currents were examined in postnatal rat hippocampal neurons using recordings from whole cells and outside-out membrane patches. 2. Rapid applications of quisqualate to whole cells and outside-out patches evoked a current that desensitized to a steady-state level. WGA blocked desensitization by increasing the steady-state current amplitude without altering the current-voltage (I-V) relationship or pharmacology of the current. 3. In outside-out patches quisqualate (2.5-1,000 microM) elicited bursts of channel openings having conductances of 2.7, 6.3, and 13 pS. The mean burst length for all conductances was 8.6 +/- 0.6 ms (mean +/- SE) and exhibited little voltage (-110 to +80 mV) or concentration (2.5-1,000 microM) dependence. Treating patches with 580 nM WGA produced no change in conductance, but the mean burst length for 100 microM quisqualate increased from 9.0 +/- 1.1 to 16 +/- 3.2 ms. 4. Fluctuation analysis of whole cell currents evoked by 1 microM quisqualate at -80 mV revealed an increase in the time constant from 8.7 +/- 0.5 to 13 +/- 1.0 ms after treatment with 580 nM WGA. This treatment produced no change in the estimated single-channel conductance. 5. These findings suggest that an increase in channel burst length, rather than an increase in single-channel conductance, contributes to the WGA-induced augmentation of the steady-state quisqualate current.", "contents": "Blockade of ionotropic quisqualate receptor desensitization by wheat germ agglutinin in cultured postnatal rat hippocampal neurons. 1. The effects of the lectin wheat germ agglutinin (WGA) on quisqualate-gated currents were examined in postnatal rat hippocampal neurons using recordings from whole cells and outside-out membrane patches. 2. Rapid applications of quisqualate to whole cells and outside-out patches evoked a current that desensitized to a steady-state level. WGA blocked desensitization by increasing the steady-state current amplitude without altering the current-voltage (I-V) relationship or pharmacology of the current. 3. In outside-out patches quisqualate (2.5-1,000 microM) elicited bursts of channel openings having conductances of 2.7, 6.3, and 13 pS. The mean burst length for all conductances was 8.6 +/- 0.6 ms (mean +/- SE) and exhibited little voltage (-110 to +80 mV) or concentration (2.5-1,000 microM) dependence. Treating patches with 580 nM WGA produced no change in conductance, but the mean burst length for 100 microM quisqualate increased from 9.0 +/- 1.1 to 16 +/- 3.2 ms. 4. Fluctuation analysis of whole cell currents evoked by 1 microM quisqualate at -80 mV revealed an increase in the time constant from 8.7 +/- 0.5 to 13 +/- 1.0 ms after treatment with 580 nM WGA. This treatment produced no change in the estimated single-channel conductance. 5. These findings suggest that an increase in channel burst length, rather than an increase in single-channel conductance, contributes to the WGA-induced augmentation of the steady-state quisqualate current."} {"id": "PMID:1283405", "title": "Wheat germ agglutinin enhances EPSCs in cultured postnatal rat hippocampal neurons by blocking ionotropic quisqualate receptor desensitization.", "content": "1. The effect of the lectin wheat germ agglutinin (WGA), an inhibitor of ionotropic quisqualate receptor desensitization, on both evoked and spontaneous fast excitatory postsynaptic events was examined in cultured postnatal rat hippocampal neurons with the use of whole cell recordings. 2. WGA, at 580 nM, potentiated evoked fast excitatory postsynaptic currents (EPSCs) by increasing the amplitudes by 100 +/- 27% (mean +/- SE) and the time constant of decay from 5.8 +/- 0.6 to 7.9 +/- 0.5 ms. The increases in these parameters were not accompanied by changes in the current-voltage (I-V) relationship or pharmacological profile of the fast EPSCs. 3. WGA did not alter the amplitude or time course of decay of inhibitory postsynaptic currents (IPSCs), and it did not alter neuronal input resistance or action potentials. 4. WGA increased the amplitude of spontaneous fast miniature EPSCs (MEPSCs), defined as spontaneous EPSCs recorded in the presence of tetrodotoxin, by 53 +/- 11% and increased the time required to decay to 50% of the peak amplitude by 48 +/- 23%. These changes were not associated with a change in the rate of MEPSC occurrence. 5. These results suggest that WGA augments hippocampal excitatory postsynaptic events via a postsynaptic mechanism. The results further imply that ionotropic quisqualate receptor desensitization can modulate the amplitude and time course of decay of fast excitatory synaptic events. Thus desensitization may be one factor that regulates fast excitatory synaptic transmission.", "contents": "Wheat germ agglutinin enhances EPSCs in cultured postnatal rat hippocampal neurons by blocking ionotropic quisqualate receptor desensitization. 1. The effect of the lectin wheat germ agglutinin (WGA), an inhibitor of ionotropic quisqualate receptor desensitization, on both evoked and spontaneous fast excitatory postsynaptic events was examined in cultured postnatal rat hippocampal neurons with the use of whole cell recordings. 2. WGA, at 580 nM, potentiated evoked fast excitatory postsynaptic currents (EPSCs) by increasing the amplitudes by 100 +/- 27% (mean +/- SE) and the time constant of decay from 5.8 +/- 0.6 to 7.9 +/- 0.5 ms. The increases in these parameters were not accompanied by changes in the current-voltage (I-V) relationship or pharmacological profile of the fast EPSCs. 3. WGA did not alter the amplitude or time course of decay of inhibitory postsynaptic currents (IPSCs), and it did not alter neuronal input resistance or action potentials. 4. WGA increased the amplitude of spontaneous fast miniature EPSCs (MEPSCs), defined as spontaneous EPSCs recorded in the presence of tetrodotoxin, by 53 +/- 11% and increased the time required to decay to 50% of the peak amplitude by 48 +/- 23%. These changes were not associated with a change in the rate of MEPSC occurrence. 5. These results suggest that WGA augments hippocampal excitatory postsynaptic events via a postsynaptic mechanism. The results further imply that ionotropic quisqualate receptor desensitization can modulate the amplitude and time course of decay of fast excitatory synaptic events. Thus desensitization may be one factor that regulates fast excitatory synaptic transmission."} {"id": "PMID:1283406", "title": "A computer-based model for realistic simulations of neural networks. II. The segmental network generating locomotor rhythmicity in the lamprey.", "content": "1. To analyze the function of the spinal interneuronal network generating locomotion in the lamprey CNS, a vertebrate model system, we performed computer simulations with realistic model neurons possessing the essential properties of their biological counterparts. 2. The segmental network has been simulated by modeling experimentally established types of neurons with their specific membrane properties and synaptic interconnections. Fictive locomotor activity, which can be experimentally induced by elevating the background excitability by bath application of excitatory amino acids, was simulated by opening membrane conductances for kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors. Kainate/AMPA receptor activation induced a rhythm in the middle and upper part of the physiological burst frequency range, whereas NMDA receptor activation evoked bursting in the lower part of the range, which corresponds well to earlier experimental findings. 3. Several factors contributing to the termination of the burst were studied and their interaction was assessed in simulations of the network. 1) The summation of spike afterhyperpolarizations (late AHPs), leading to adaptation of the discharge, acts as a primary burst-terminating factor at lower rates of kainate/AMPA-induced bursting, and it also interacts with the NMDA-induced oscillatory membrane properties during slow rhythmicity. 2) The termination of the depolarized NMDA plateau is another important factor during NMDA-evoked rhythmicity. 3) The synaptic inhibition from lateral interneurons to the interneurons mediating reciprocal inhibition is important at higher rates of kainate/AMPA-induced bursting. 4. The mechanism of action of 5-hydroxytryptamine (5-HT) on the lamprey segmental network was further investigated by simulation. 5-HT is known to lower the burst frequency during fictive locomotion and also to decrease the conductance through the Ca(2+)-dependent K+ channels, and thereby the size of the late AHP that follows the action potential. Decreasing this conductance in the network simulations resulted in a lesser amount of AHP summation and thereby less frequency adaptation during the burst, longer bursts, and a lower locomotor frequency. Thus the selective action of 5-HT on the Ca(2+)-dependent K+ channels, and hence on the AHP, can account for the modulatory effect on the fictive locomotor rhythm seen experimentally. 5. The results demonstrate that the present simulation of the segmental network can account for essential features of the motor pattern seen experimentally during lamprey locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "A computer-based model for realistic simulations of neural networks. II. The segmental network generating locomotor rhythmicity in the lamprey. 1. To analyze the function of the spinal interneuronal network generating locomotion in the lamprey CNS, a vertebrate model system, we performed computer simulations with realistic model neurons possessing the essential properties of their biological counterparts. 2. The segmental network has been simulated by modeling experimentally established types of neurons with their specific membrane properties and synaptic interconnections. Fictive locomotor activity, which can be experimentally induced by elevating the background excitability by bath application of excitatory amino acids, was simulated by opening membrane conductances for kainate/alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors. Kainate/AMPA receptor activation induced a rhythm in the middle and upper part of the physiological burst frequency range, whereas NMDA receptor activation evoked bursting in the lower part of the range, which corresponds well to earlier experimental findings. 3. Several factors contributing to the termination of the burst were studied and their interaction was assessed in simulations of the network. 1) The summation of spike afterhyperpolarizations (late AHPs), leading to adaptation of the discharge, acts as a primary burst-terminating factor at lower rates of kainate/AMPA-induced bursting, and it also interacts with the NMDA-induced oscillatory membrane properties during slow rhythmicity. 2) The termination of the depolarized NMDA plateau is another important factor during NMDA-evoked rhythmicity. 3) The synaptic inhibition from lateral interneurons to the interneurons mediating reciprocal inhibition is important at higher rates of kainate/AMPA-induced bursting. 4. The mechanism of action of 5-hydroxytryptamine (5-HT) on the lamprey segmental network was further investigated by simulation. 5-HT is known to lower the burst frequency during fictive locomotion and also to decrease the conductance through the Ca(2+)-dependent K+ channels, and thereby the size of the late AHP that follows the action potential. Decreasing this conductance in the network simulations resulted in a lesser amount of AHP summation and thereby less frequency adaptation during the burst, longer bursts, and a lower locomotor frequency. Thus the selective action of 5-HT on the Ca(2+)-dependent K+ channels, and hence on the AHP, can account for the modulatory effect on the fictive locomotor rhythm seen experimentally. 5. The results demonstrate that the present simulation of the segmental network can account for essential features of the motor pattern seen experimentally during lamprey locomotion.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1283407", "title": "Calcium-activated chloride channels in cultured embryonic Xenopus spinal neurons.", "content": "1. Single-channel currents were recorded from Xenopus spinal neurons developing in vitro using the patch-clamp technique, to identify the channels underlying the large and small macroscopic Ca(2+)-activated Cl- currents (ICl(Ca)) present in these cells. 2. Channels of large (maxi-channels; 310 pS) and smaller conductance (mini-channels; 50-60 pS) are activated by elevation of cytoplasmic Ca2+ concentration. Channel activity is not altered by subsequent removal of Ca2+ from the bath, arguing against a direct ligand-type Ca2+ dependence. The much higher incidence of channel activation in cell-attached patches from cells permeabilized with the Ca2+ ionophore A23187 than in excised patches also suggests the involvement of some unidentified intracellular factor. 3. The reversal potential of maxi-Cl- channels is not altered by changes in Na+ concentration, but is shifted in the negative direction by the substitution of Cl- by methanesulfonate on the intracellular side of the patch, indicating their anionic selectivity. 4. Maxi-Cl- channels exhibited the presence of multiple probable subconductance states and showed marked voltage-dependent inactivation above and below +/- 20 mV. 5. Examination of maxi-Cl- channels at early times in culture (6-9 h) and 24 h later did not reveal any developmental change in the characteristics described above. However, the mean open duration of the channel was found to increase twofold during this period of time. 6. The simultaneous presence of maxi- and mini-Cl- channels prevented detailed characterization of the latter. The anionic selectivity of mini-Cl- channels is suggested by their reversal potential that lies close to the Cl- equilibrium potential.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Calcium-activated chloride channels in cultured embryonic Xenopus spinal neurons. 1. Single-channel currents were recorded from Xenopus spinal neurons developing in vitro using the patch-clamp technique, to identify the channels underlying the large and small macroscopic Ca(2+)-activated Cl- currents (ICl(Ca)) present in these cells. 2. Channels of large (maxi-channels; 310 pS) and smaller conductance (mini-channels; 50-60 pS) are activated by elevation of cytoplasmic Ca2+ concentration. Channel activity is not altered by subsequent removal of Ca2+ from the bath, arguing against a direct ligand-type Ca2+ dependence. The much higher incidence of channel activation in cell-attached patches from cells permeabilized with the Ca2+ ionophore A23187 than in excised patches also suggests the involvement of some unidentified intracellular factor. 3. The reversal potential of maxi-Cl- channels is not altered by changes in Na+ concentration, but is shifted in the negative direction by the substitution of Cl- by methanesulfonate on the intracellular side of the patch, indicating their anionic selectivity. 4. Maxi-Cl- channels exhibited the presence of multiple probable subconductance states and showed marked voltage-dependent inactivation above and below +/- 20 mV. 5. Examination of maxi-Cl- channels at early times in culture (6-9 h) and 24 h later did not reveal any developmental change in the characteristics described above. However, the mean open duration of the channel was found to increase twofold during this period of time. 6. The simultaneous presence of maxi- and mini-Cl- channels prevented detailed characterization of the latter. The anionic selectivity of mini-Cl- channels is suggested by their reversal potential that lies close to the Cl- equilibrium potential.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283408", "title": "[An immunohistological study of normal parotid gland].", "content": "Cytoskeletal proteins from each epithelial component of the parotid gland were studied immunohistologically using monospecific monoclonal antibodies, and we obtained several interesting results: 1) The expression of vimentin, S-100 protein and GFAP were essentially unrecognizable. 2) The expression of alpha-actin was recognized only in myoepithelial cells, and was negative in other tissues. 3) The expression of CK-3, CK-6, CK-7, CK-8 and CK-18 was commonly recognized in both acinal and ductal cells. 4) The expression of CK-13 and CK-19 was recognized in ductal cells, but was negative in acinal cells. 5) We propose that the characteristic cell be referred to as a \"duct satellite cell\", as it comprises part of the intercalated duct and is sporadically localized around striated and layer ducts. 6) These duct satellite cells express all subclasses of cytokeratin observed in myoepithelial, acinal and ductal cells. 7) The duct satellite cells observed in this study are most likely to correspond to the undifferentiated reserve cells described in \"bicellular theory\", and we speculate that all epithelial tissues of the parotid gland originate from these cells.", "contents": "[An immunohistological study of normal parotid gland]. Cytoskeletal proteins from each epithelial component of the parotid gland were studied immunohistologically using monospecific monoclonal antibodies, and we obtained several interesting results: 1) The expression of vimentin, S-100 protein and GFAP were essentially unrecognizable. 2) The expression of alpha-actin was recognized only in myoepithelial cells, and was negative in other tissues. 3) The expression of CK-3, CK-6, CK-7, CK-8 and CK-18 was commonly recognized in both acinal and ductal cells. 4) The expression of CK-13 and CK-19 was recognized in ductal cells, but was negative in acinal cells. 5) We propose that the characteristic cell be referred to as a \"duct satellite cell\", as it comprises part of the intercalated duct and is sporadically localized around striated and layer ducts. 6) These duct satellite cells express all subclasses of cytokeratin observed in myoepithelial, acinal and ductal cells. 7) The duct satellite cells observed in this study are most likely to correspond to the undifferentiated reserve cells described in \"bicellular theory\", and we speculate that all epithelial tissues of the parotid gland originate from these cells."} {"id": "PMID:1283410", "title": "Abdominal pain as a cause of acute admission to hospital.", "content": "Between 1 January 1988 and 31 December 1989, 525 patients were admitted to one hospital with a diagnosis of acute abdominal pain. Of these, 182 (34.7%) underwent an emergency operation and 14 (7.7%) of these patients subsequently died within 30 days. Death was due to intestinal obstruction in 69%, and there was a 28% mortality rate for emergency colonic resection. Non-specific abdominal pain (NSAP) was the most common diagnosis (36.0%), followed by appendicitis (14.9%) and urological causes (12.8%). There was an unnecessary appendicectomy rate of 25.0%. Admission with pain because of urological causes was over twice that of previous reports. Duration of stay increased greatly with age. Results from this study confirm the high mortality rate in the elderly from emergency colonic resection. Greater care in diagnosis and a conservative approach to appendicitis, with laparoscopy in females of reproductive age, may produce a lower unnecessary appendicectomy rate without an increase in morbidity. If the diagnosis of NSAP could be made earlier and patients discharged sooner, a large saving in resources would result. This early diagnosis is not yet possible.", "contents": "Abdominal pain as a cause of acute admission to hospital. Between 1 January 1988 and 31 December 1989, 525 patients were admitted to one hospital with a diagnosis of acute abdominal pain. Of these, 182 (34.7%) underwent an emergency operation and 14 (7.7%) of these patients subsequently died within 30 days. Death was due to intestinal obstruction in 69%, and there was a 28% mortality rate for emergency colonic resection. Non-specific abdominal pain (NSAP) was the most common diagnosis (36.0%), followed by appendicitis (14.9%) and urological causes (12.8%). There was an unnecessary appendicectomy rate of 25.0%. Admission with pain because of urological causes was over twice that of previous reports. Duration of stay increased greatly with age. Results from this study confirm the high mortality rate in the elderly from emergency colonic resection. Greater care in diagnosis and a conservative approach to appendicitis, with laparoscopy in females of reproductive age, may produce a lower unnecessary appendicectomy rate without an increase in morbidity. If the diagnosis of NSAP could be made earlier and patients discharged sooner, a large saving in resources would result. This early diagnosis is not yet possible."} {"id": "PMID:1283411", "title": "Preoperative shaving: patient and surgeon preferences and complications for the Gillies incision.", "content": "A modified technique for the Gillies temporal approach without previous hair removal is described. A randomized prospective study of two groups of patients requiring elevation of fractures of the zygomaticomalar complex via this approach with and without hair removal was performed with respect to patients' attitudes and surgeons' assessment.", "contents": "Preoperative shaving: patient and surgeon preferences and complications for the Gillies incision. A modified technique for the Gillies temporal approach without previous hair removal is described. A randomized prospective study of two groups of patients requiring elevation of fractures of the zygomaticomalar complex via this approach with and without hair removal was performed with respect to patients' attitudes and surgeons' assessment."} {"id": "PMID:1283412", "title": "Antiphospholipid antibodies: new perspectives on antigenic specificity.", "content": "Antiphospholipid antibodies (aPL) are found in up to 60% of patients with systemic lupus erythematosus (SLE), and appear to predispose to a number of complications of the disease. We purified IgG from patients with SLE and the antiphospholipid antibody syndrome (APS) who have high levels of aPL and used this IgG in a modified ELISA where we excluded any source of cofactor in the assay. We showed that for 10 of the 11 patients, IgG bound strongly to cardiolipin only in the presence of the cofactor, which was present in fetal calf serum, normal human serum (NHS), and in the infranatant lipoprotein fractions obtained by flotation ultracentrifugation of NHS. We then purified beta 2 glycoprotein I (beta 2GPI) from NHS and showed that for 9 of the 11 samples of IgG, beta 2GPI was as effective, or more effective, than NHS as a source of cofactor. When beta 2GPI was coated on ELISA plate and used as an antigen we found little or no reactivity of patient sera or IgG, suggesting that beta 2GPI alone is not antigenic in our system. Three possible explanations could be put forward to explain the behavior of cardiolipin and beta 2GPI, neither of which is antigenic alone.", "contents": "Antiphospholipid antibodies: new perspectives on antigenic specificity. Antiphospholipid antibodies (aPL) are found in up to 60% of patients with systemic lupus erythematosus (SLE), and appear to predispose to a number of complications of the disease. We purified IgG from patients with SLE and the antiphospholipid antibody syndrome (APS) who have high levels of aPL and used this IgG in a modified ELISA where we excluded any source of cofactor in the assay. We showed that for 10 of the 11 patients, IgG bound strongly to cardiolipin only in the presence of the cofactor, which was present in fetal calf serum, normal human serum (NHS), and in the infranatant lipoprotein fractions obtained by flotation ultracentrifugation of NHS. We then purified beta 2 glycoprotein I (beta 2GPI) from NHS and showed that for 9 of the 11 samples of IgG, beta 2GPI was as effective, or more effective, than NHS as a source of cofactor. When beta 2GPI was coated on ELISA plate and used as an antigen we found little or no reactivity of patient sera or IgG, suggesting that beta 2GPI alone is not antigenic in our system. Three possible explanations could be put forward to explain the behavior of cardiolipin and beta 2GPI, neither of which is antigenic alone."} {"id": "PMID:1283413", "title": "Apical and basolateral Na/H exchange in cultured murine proximal tubule cells (MCT): effect of parathyroid hormone (PTH).", "content": "Kidney proximal tubule Na/H exchange is inhibited by PTH. To analyze further the cellular mechanisms involved in this regulation we have used MCT cells (a culture of SV-40 immortalized mouse cortical tubule cells) grown on permeant filter supports. Na/H exchange was measured using single cell fluorescence microscopy (BCECF) and phosphate transport (measured for comparisons) by tracer techniques. MCT cells express apical and basolateral Na/H exchangers which respond differently to inhibition by ethylisopropylamiloride and by dimethylamiloride, the basolateral membrane transporter being more sensitive. Apical membrane Na/H exchange was inhibited by PTH (10(-8) M; by an average of 25%); similar degrees of inhibition were observed when cells were exposed either to forskolin, 8-bromo-cAMP or phorbol ester. Basolateral membrane Na/H exchange was stimulated either by incubation with PTH (to 129% above control levels) or by addition of phorbol ester (to 120% above control levels); it was inhibited after exposure to either forskolin or 8-bromo-cAMP. The above effects of PTH and phorbol ester (apical and basolateral) were prevented by preincubation of cells with protein kinase C antagonists, staurosporine and calphostin C; both compounds did not affect forskolin or 8-bromo-cAMP induced effects. PTH also inhibited apical Na-dependent phosphate influx (29% inhibition at 10(-8) M); it had no effect on basolateral phosphate fluxes (Na-dependent and Na-independent). Incubation with PTH (10(-8) M) resulted in a rapid and transient increase in [Ca2+]i (measured with the fluorescent indicator, fura-2), due to stimulation of a Ca2+ release from intracellular stores. Exposure of MCT cells to PTH did not elevate cellular levels of cAMP. Taken together, these results suggest that PTH utilizes in MCT cells the phospholipase C/protein kinase C pathway to differently control Na/H exchangers (apical vs. basolateral) and to inhibit apical Na/Pi cotransport.", "contents": "Apical and basolateral Na/H exchange in cultured murine proximal tubule cells (MCT): effect of parathyroid hormone (PTH). Kidney proximal tubule Na/H exchange is inhibited by PTH. To analyze further the cellular mechanisms involved in this regulation we have used MCT cells (a culture of SV-40 immortalized mouse cortical tubule cells) grown on permeant filter supports. Na/H exchange was measured using single cell fluorescence microscopy (BCECF) and phosphate transport (measured for comparisons) by tracer techniques. MCT cells express apical and basolateral Na/H exchangers which respond differently to inhibition by ethylisopropylamiloride and by dimethylamiloride, the basolateral membrane transporter being more sensitive. Apical membrane Na/H exchange was inhibited by PTH (10(-8) M; by an average of 25%); similar degrees of inhibition were observed when cells were exposed either to forskolin, 8-bromo-cAMP or phorbol ester. Basolateral membrane Na/H exchange was stimulated either by incubation with PTH (to 129% above control levels) or by addition of phorbol ester (to 120% above control levels); it was inhibited after exposure to either forskolin or 8-bromo-cAMP. The above effects of PTH and phorbol ester (apical and basolateral) were prevented by preincubation of cells with protein kinase C antagonists, staurosporine and calphostin C; both compounds did not affect forskolin or 8-bromo-cAMP induced effects. PTH also inhibited apical Na-dependent phosphate influx (29% inhibition at 10(-8) M); it had no effect on basolateral phosphate fluxes (Na-dependent and Na-independent). Incubation with PTH (10(-8) M) resulted in a rapid and transient increase in [Ca2+]i (measured with the fluorescent indicator, fura-2), due to stimulation of a Ca2+ release from intracellular stores. Exposure of MCT cells to PTH did not elevate cellular levels of cAMP. Taken together, these results suggest that PTH utilizes in MCT cells the phospholipase C/protein kinase C pathway to differently control Na/H exchangers (apical vs. basolateral) and to inhibit apical Na/Pi cotransport."} {"id": "PMID:1283414", "title": "Anion and cation permeability of a large conductance anion channel in the T84 human colonic cell line.", "content": "A large conductance multi-state channel was identified and characterized in single channel recordings from cell-attached and excised patches of the human colonic tumor cell line, T84. The channel activity was dependent on the presence of both permeable cations and anions. In Na(+)-free symmetrical Cl- solutions or Cl(-)-free symmetrical Na+ solutions the channel was inactive. Addition of 5 mM NaCl (NaI or KCl) induced channel activity. The selectivity sequence obtained from the shift in reversal potential was I- (1.9) > Cl- (1) > Na+ (0.5) > K+ (0.3). SO2-(4), SCN- (thiocyanate) and NMDG+ were impermeant. Multiple subconductance states were identified at all voltages explored (+/- 90 mV). The minimum conductance encountered in symmetrical 100 mM NaCl was a 15 pS substrate, the maximum, 210 pS. The channel appeared to be composed of multiples of the 15 pS subunits which were reversibly blocked by the loop diuretic bumetanide (5 microM).", "contents": "Anion and cation permeability of a large conductance anion channel in the T84 human colonic cell line. A large conductance multi-state channel was identified and characterized in single channel recordings from cell-attached and excised patches of the human colonic tumor cell line, T84. The channel activity was dependent on the presence of both permeable cations and anions. In Na(+)-free symmetrical Cl- solutions or Cl(-)-free symmetrical Na+ solutions the channel was inactive. Addition of 5 mM NaCl (NaI or KCl) induced channel activity. The selectivity sequence obtained from the shift in reversal potential was I- (1.9) > Cl- (1) > Na+ (0.5) > K+ (0.3). SO2-(4), SCN- (thiocyanate) and NMDG+ were impermeant. Multiple subconductance states were identified at all voltages explored (+/- 90 mV). The minimum conductance encountered in symmetrical 100 mM NaCl was a 15 pS substrate, the maximum, 210 pS. The channel appeared to be composed of multiples of the 15 pS subunits which were reversibly blocked by the loop diuretic bumetanide (5 microM)."} {"id": "PMID:1283415", "title": "Sonographic scoring index for prenatal detection of chromosomal abnormalities.", "content": "Current indications for cytogenetic evaluation leave the majority of Down syndrome fetuses undetected. Using advanced maternal age and low maternal serum alpha-fetoprotein (AFP) levels as criteria, only 40% of fetuses with Down syndrome (trisomy 21) are identified (positive predictive value, 0.4% to 1%). We evaluate the sonographically detectable physical features of second trimester fetuses to determine whether these features are more sensitive and specific than maternal age for detecting fetuses with abnormal karyotypes. From March 1, 1990, to September 1, 1991, more than 5,000 fetuses between 14 and 20 weeks of development were referred for genetic amniocentesis because of advanced maternal age or abnormal AFP levels. Forty-three of these 5,000 fetuses were later found to have autosomal trisomies by karyotype (32 with trisomy 21, nine with trisomy 18, and two with trisomy 13). A sample of 588 consecutive normal fetuses from the total of more than 5,000 amniocenteses performed during this period of time was used as our control group for statistical analysis. The sonographic features of these 588 normal second trimester fetuses and the 43 trisomic fetuses recorded prospectively prior to knowledge of the karyotype were evaluated statistically. The femur and humerus lengths, nuchal fold, renal pelvic dimension, and major structural defects were compared in the normal and trisomic fetuses. On the basis of our results, a weighted sonographic score was developed to optimize the detection of fetuses at risk for aneuploidy. Using our previously published formulas and criteria for a short femur and humerus, 17/32 (53%) fetuses with Down syndrome and 23/588 (3.9%) of the normal fetuses were identified. Twenty two of 32 Down syndrome fetuses (69%) and 2/588 (0.34%) of normals had a nuchal fold > or = 6 mm, and 11 of 32 Down syndrome fetuses and all those with trisomies 18 and 13 had a major anomaly detected sonographically. The following scoring system was developed for the detection of aneuploidy: nuchal fold = 2, major structural defect = 2, and short femur, short humerus, and pyelectasis = 1 each. Selecting fetuses with a score of > or = 2 would identify 26/32 (81%) Down syndrome fetuses, and 9/9 (100%) and 2/2 (100%) fetuses with trisomies 18 and 13 respectively, but only 26/588 (4.4%) of the normal fetuses. Using the sonographic score of 2 results in a positive predictive value for a 1/250 risk group of 6.87% for identifying Down syndrome fetuses and 7.25% for all three trisomies.(ABSTRACT TRUNCATED AT 400 WORDS)", "contents": "Sonographic scoring index for prenatal detection of chromosomal abnormalities. Current indications for cytogenetic evaluation leave the majority of Down syndrome fetuses undetected. Using advanced maternal age and low maternal serum alpha-fetoprotein (AFP) levels as criteria, only 40% of fetuses with Down syndrome (trisomy 21) are identified (positive predictive value, 0.4% to 1%). We evaluate the sonographically detectable physical features of second trimester fetuses to determine whether these features are more sensitive and specific than maternal age for detecting fetuses with abnormal karyotypes. From March 1, 1990, to September 1, 1991, more than 5,000 fetuses between 14 and 20 weeks of development were referred for genetic amniocentesis because of advanced maternal age or abnormal AFP levels. Forty-three of these 5,000 fetuses were later found to have autosomal trisomies by karyotype (32 with trisomy 21, nine with trisomy 18, and two with trisomy 13). A sample of 588 consecutive normal fetuses from the total of more than 5,000 amniocenteses performed during this period of time was used as our control group for statistical analysis. The sonographic features of these 588 normal second trimester fetuses and the 43 trisomic fetuses recorded prospectively prior to knowledge of the karyotype were evaluated statistically. The femur and humerus lengths, nuchal fold, renal pelvic dimension, and major structural defects were compared in the normal and trisomic fetuses. On the basis of our results, a weighted sonographic score was developed to optimize the detection of fetuses at risk for aneuploidy. Using our previously published formulas and criteria for a short femur and humerus, 17/32 (53%) fetuses with Down syndrome and 23/588 (3.9%) of the normal fetuses were identified. Twenty two of 32 Down syndrome fetuses (69%) and 2/588 (0.34%) of normals had a nuchal fold > or = 6 mm, and 11 of 32 Down syndrome fetuses and all those with trisomies 18 and 13 had a major anomaly detected sonographically. The following scoring system was developed for the detection of aneuploidy: nuchal fold = 2, major structural defect = 2, and short femur, short humerus, and pyelectasis = 1 each. Selecting fetuses with a score of > or = 2 would identify 26/32 (81%) Down syndrome fetuses, and 9/9 (100%) and 2/2 (100%) fetuses with trisomies 18 and 13 respectively, but only 26/588 (4.4%) of the normal fetuses. Using the sonographic score of 2 results in a positive predictive value for a 1/250 risk group of 6.87% for identifying Down syndrome fetuses and 7.25% for all three trisomies.(ABSTRACT TRUNCATED AT 400 WORDS)"} {"id": "PMID:1283416", "title": "[Application of PCR and RT-PCR method to molecular biology study in nephrology].", "content": "Recent advance in molecular biology and genetic engineering has made a profound influence on basic and clinical medicine. Development of PCR (polymerase chain reaction) has transformed our trend of thought in molecular biology. Applications of PCR method has extended to nephrology study. RT (reverse transcription)-PCR method was elaborated to identify mRNA even in a small number of cells. It is also important and advantageous that PCR facilitates the utilization of a non-radioisotopic detection system. Newly developed chemiluminescent procedure yields as high sensitivity just as radioactive probes. Further applications are now being investigated including in situ PCR. PCR and RT-PCR methods are of great value for studying a molecular biological background of intricate kidney functions and diverse renal disorders.", "contents": "[Application of PCR and RT-PCR method to molecular biology study in nephrology]. Recent advance in molecular biology and genetic engineering has made a profound influence on basic and clinical medicine. Development of PCR (polymerase chain reaction) has transformed our trend of thought in molecular biology. Applications of PCR method has extended to nephrology study. RT (reverse transcription)-PCR method was elaborated to identify mRNA even in a small number of cells. It is also important and advantageous that PCR facilitates the utilization of a non-radioisotopic detection system. Newly developed chemiluminescent procedure yields as high sensitivity just as radioactive probes. Further applications are now being investigated including in situ PCR. PCR and RT-PCR methods are of great value for studying a molecular biological background of intricate kidney functions and diverse renal disorders."} {"id": "PMID:1283417", "title": "[Endothelin, EDRF, CGRP].", "content": "Endothelin-1 is now known to synthesized in the kidney and influence the renal function. ET-1 mRNA was detected in glomerulus and inner medullary collecting ducts using RT-PCR technique. ETA receptor mRNA was detected only in glomerulus, vasa recta bundle, and arcuate artery. ETB receptor mRNA distributed mainly in glomerulus and collecting ducts. Endothelium derived relaxing factor (EDRF) was believed to be nitric oxide, was synthesized by nitric oxide (NO) synthase from L-arginine. NO stimulates soluble guanylate cyclase and increases cGMP level. NO synthase mRNA was detected in glomerulus and inner medulla. Soluble guanylate cyclase mRNA distributed widely along the nephron segments. NO and cGMP system seems to play some roles in modulating renal functions.", "contents": "[Endothelin, EDRF, CGRP]. Endothelin-1 is now known to synthesized in the kidney and influence the renal function. ET-1 mRNA was detected in glomerulus and inner medullary collecting ducts using RT-PCR technique. ETA receptor mRNA was detected only in glomerulus, vasa recta bundle, and arcuate artery. ETB receptor mRNA distributed mainly in glomerulus and collecting ducts. Endothelium derived relaxing factor (EDRF) was believed to be nitric oxide, was synthesized by nitric oxide (NO) synthase from L-arginine. NO stimulates soluble guanylate cyclase and increases cGMP level. NO synthase mRNA was detected in glomerulus and inner medulla. Soluble guanylate cyclase mRNA distributed widely along the nephron segments. NO and cGMP system seems to play some roles in modulating renal functions."} {"id": "PMID:1283418", "title": "[Ion channels in the kidney: molecular biological aspects].", "content": "Ion channels in renal tubules are involved in maintenance of the volume and ion composition of the body. In the kidney these channels are expressed at the apical and/or basolateral cell membranes and are responsible for vectorial ion transport. Structure and function of the renal ion channels differs from those of previous channels which were cloned in excitable tissues. In this review I outline the various types of ion channels in renal and non-renal cells and give examples that emphasize the physiological roles of these channels in the nephron.", "contents": "[Ion channels in the kidney: molecular biological aspects]. Ion channels in renal tubules are involved in maintenance of the volume and ion composition of the body. In the kidney these channels are expressed at the apical and/or basolateral cell membranes and are responsible for vectorial ion transport. Structure and function of the renal ion channels differs from those of previous channels which were cloned in excitable tissues. In this review I outline the various types of ion channels in renal and non-renal cells and give examples that emphasize the physiological roles of these channels in the nephron."} {"id": "PMID:1283419", "title": "[DNA typing of HLA-class II genes in idiopathic nephropathy].", "content": "The association between idiopathic nephropathy and HLA-class II antigen has been reported in many ethnic groups. We attempted to ascertain the HLA regions more specifically, associated with Japanese idiopathic membranous nephropathy (IMN), IgA nephropathy (IgAN) and minimal change nephrotic syndrome (MCNS), by examining HLA-class II genes. DNA typing of HLA-class II genes showed that IMN was associated with HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602, IgA with HLA-DQA1*0301, and MCNS with DQB1*0302. We also found a common epitope of HLA-class II (at 38th amino acid position of HLA-DR beta in IMN, at 55th of HLA-DQ beta in MCNS) in Japanese and Caucasian patients. These particular epitopes seem to be important for the susceptibility to IMN or MCNS.", "contents": "[DNA typing of HLA-class II genes in idiopathic nephropathy]. The association between idiopathic nephropathy and HLA-class II antigen has been reported in many ethnic groups. We attempted to ascertain the HLA regions more specifically, associated with Japanese idiopathic membranous nephropathy (IMN), IgA nephropathy (IgAN) and minimal change nephrotic syndrome (MCNS), by examining HLA-class II genes. DNA typing of HLA-class II genes showed that IMN was associated with HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602, IgA with HLA-DQA1*0301, and MCNS with DQB1*0302. We also found a common epitope of HLA-class II (at 38th amino acid position of HLA-DR beta in IMN, at 55th of HLA-DQ beta in MCNS) in Japanese and Caucasian patients. These particular epitopes seem to be important for the susceptibility to IMN or MCNS."} {"id": "PMID:1283420", "title": "[The molecular genetic analysis of polycystic kidney disease].", "content": "Autosomal dominant polycystic kidney disease (ADPKD) is one of common single gene disorders. The development of molecular genetic techniques has shown that mutant PKD1 gene assigned to ADPKD was closely linked to alpha-globin on the short arm of chromosome 16. This location was established when genetic linkage was found between ADPKD and a highly polymorphic region at the 3' end of the alpha-globin cluster (3' HVR). The discover of genetic linkage markers such as 3' HVR probe has provided a diagnostic test in presymptomatic stage. We performed this diagnostic test using DNA probes in 3 patients with ADPKD of one Japanese family. They also showed PKD1 gene linkage as previously described by Reeders et al. Linkage analysis of the PKD1 gene might be available to diagnostic test of ADPKD. DNA diagnosis of ADPKD however has to be performed carefully because of an ethical standpoint.", "contents": "[The molecular genetic analysis of polycystic kidney disease]. Autosomal dominant polycystic kidney disease (ADPKD) is one of common single gene disorders. The development of molecular genetic techniques has shown that mutant PKD1 gene assigned to ADPKD was closely linked to alpha-globin on the short arm of chromosome 16. This location was established when genetic linkage was found between ADPKD and a highly polymorphic region at the 3' end of the alpha-globin cluster (3' HVR). The discover of genetic linkage markers such as 3' HVR probe has provided a diagnostic test in presymptomatic stage. We performed this diagnostic test using DNA probes in 3 patients with ADPKD of one Japanese family. They also showed PKD1 gene linkage as previously described by Reeders et al. Linkage analysis of the PKD1 gene might be available to diagnostic test of ADPKD. DNA diagnosis of ADPKD however has to be performed carefully because of an ethical standpoint."} {"id": "PMID:1283421", "title": "Histamine-induced depolarization and the cyclic AMP--protein kinase A system in isolated guinea pig adipocytes.", "content": "The relationship between histamine (Hi)-induced depolarization and the cyclic AMP system in adipocytes was studied in guinea pigs, which seem to be more sensitive than rats to Hi. Hi caused a dose-dependent depolarization in guinea pig mesenterial and epididymal adipocytes with EC50 values of 1.69 x 10(-7) M and 1.19 x 10(-7) M, respectively. Guinea pig adipocytes were 280-750 times more sensitive than rat adipocytes to Hi. Isoproterenol, forskolin and 3-isobutyl-1-methylxanthine (IBMX) also caused a depolarization, and the slopes of the concentration response lines for these drugs were almost the same as that for Hi. Furthermore, pretreatment with these drugs resulted in a potentiation of Hi-induced depolarization at lower concentrations which are not effective when each drug is used alone. In addition, Hi-induced depolarization was inhibited by pretreatment with prostaglandin E1 (PGE1) and insulin dose-dependently. The content of cyclic AMP in adipocytes was increased by Hi (10(-7) M) in association with a decrease in membrane potential. KT5720, a protein kinase A inhibitor, which provides no significant effect even at a concentration of 10(-6) M, showed an antagonistic effect on Hi-induced depolarization.", "contents": "Histamine-induced depolarization and the cyclic AMP--protein kinase A system in isolated guinea pig adipocytes. The relationship between histamine (Hi)-induced depolarization and the cyclic AMP system in adipocytes was studied in guinea pigs, which seem to be more sensitive than rats to Hi. Hi caused a dose-dependent depolarization in guinea pig mesenterial and epididymal adipocytes with EC50 values of 1.69 x 10(-7) M and 1.19 x 10(-7) M, respectively. Guinea pig adipocytes were 280-750 times more sensitive than rat adipocytes to Hi. Isoproterenol, forskolin and 3-isobutyl-1-methylxanthine (IBMX) also caused a depolarization, and the slopes of the concentration response lines for these drugs were almost the same as that for Hi. Furthermore, pretreatment with these drugs resulted in a potentiation of Hi-induced depolarization at lower concentrations which are not effective when each drug is used alone. In addition, Hi-induced depolarization was inhibited by pretreatment with prostaglandin E1 (PGE1) and insulin dose-dependently. The content of cyclic AMP in adipocytes was increased by Hi (10(-7) M) in association with a decrease in membrane potential. KT5720, a protein kinase A inhibitor, which provides no significant effect even at a concentration of 10(-6) M, showed an antagonistic effect on Hi-induced depolarization."} {"id": "PMID:1283422", "title": "Significant role of peptide leukotrienes (p-LTs) in the antigen-induced contractions of human and guinea pig lung parenchymas and bronchi or tracheas in vitro.", "content": "Chemical mediators responsible for the antigen-induced contractions of isolated, passively sensitized human and guinea pig lung parenchymas and bronchi or tracheas were evaluated by several antagonists and enzyme inhibitors, with emphasis on the effects of the potent and selective peptide leukotriene (p-LT) antagonist MCI-826. All of these preparations showed long-lasting contractions in response to an antigen challenge which lasted for more than 60 min. In either the human lung parenchyma and brochus or guinea pig lung parenchyma, pretreatment with 10(6) g/ml (2.4 x 10)-6) M) MCI-826 significantly inhibited the late phase at 10 to 60 min after the challenge of the contraction following slight suppression of the early phase. The early phase contractions of these preparations were moderately antagonized by 10(-6) g/ml mepyramine, but the late phases were not influenced or even rather enhanced. The combination treatment of MCI-826 with mepyramine additionally and markedly inhibited both phases of these preparations. On the other hand, although mepyramine apparently inhibited the early phase of the guinea pig tracheal contraction but not the late phase, no synergistic inhibitions of the contraction were observed when it was combined with MCI-826. The p-LT antagonist FPL 55712, atropine and indomethacin at 10(-6) g/ml either slightly inhibited or enhanced the contractions of human lung parenchymas, guinea pig tracheas and lung parenchymas, but the effects were not significant. From these results, it should be emphasized that p-LTs largely contribute to induction of the anaphylactic contractions of human lung parenchymas as well as human bronchi and guinea pig lung parenchymas but not guinea pig tracheas.", "contents": "Significant role of peptide leukotrienes (p-LTs) in the antigen-induced contractions of human and guinea pig lung parenchymas and bronchi or tracheas in vitro. Chemical mediators responsible for the antigen-induced contractions of isolated, passively sensitized human and guinea pig lung parenchymas and bronchi or tracheas were evaluated by several antagonists and enzyme inhibitors, with emphasis on the effects of the potent and selective peptide leukotriene (p-LT) antagonist MCI-826. All of these preparations showed long-lasting contractions in response to an antigen challenge which lasted for more than 60 min. In either the human lung parenchyma and brochus or guinea pig lung parenchyma, pretreatment with 10(6) g/ml (2.4 x 10)-6) M) MCI-826 significantly inhibited the late phase at 10 to 60 min after the challenge of the contraction following slight suppression of the early phase. The early phase contractions of these preparations were moderately antagonized by 10(-6) g/ml mepyramine, but the late phases were not influenced or even rather enhanced. The combination treatment of MCI-826 with mepyramine additionally and markedly inhibited both phases of these preparations. On the other hand, although mepyramine apparently inhibited the early phase of the guinea pig tracheal contraction but not the late phase, no synergistic inhibitions of the contraction were observed when it was combined with MCI-826. The p-LT antagonist FPL 55712, atropine and indomethacin at 10(-6) g/ml either slightly inhibited or enhanced the contractions of human lung parenchymas, guinea pig tracheas and lung parenchymas, but the effects were not significant. From these results, it should be emphasized that p-LTs largely contribute to induction of the anaphylactic contractions of human lung parenchymas as well as human bronchi and guinea pig lung parenchymas but not guinea pig tracheas."} {"id": "PMID:1283423", "title": "Calcium channel blocker-like action of reserpine in smooth muscle.", "content": "The effect of reserpine on vascular and intestinal smooth muscles was examined. In these muscles, reserpine inhibited the high K(+)-induced contraction, and this inhibitory effect was antagonized by the increase in external Ca2+ concentration and also by a Ca2+ channel activator, Bay k8644. In rabbit aorta, increases in cytosolic Ca2+ level and muscle tension due to high K+ were inhibited in parallel by reserpine. These results suggest that reserpine inhibits L-type Ca2+ channels to inhibit smooth muscle contraction.", "contents": "Calcium channel blocker-like action of reserpine in smooth muscle. The effect of reserpine on vascular and intestinal smooth muscles was examined. In these muscles, reserpine inhibited the high K(+)-induced contraction, and this inhibitory effect was antagonized by the increase in external Ca2+ concentration and also by a Ca2+ channel activator, Bay k8644. In rabbit aorta, increases in cytosolic Ca2+ level and muscle tension due to high K+ were inhibited in parallel by reserpine. These results suggest that reserpine inhibits L-type Ca2+ channels to inhibit smooth muscle contraction."} {"id": "PMID:1283424", "title": "Effects of nitric oxide synthase inhibitors on gastric alkaline secretion in rats.", "content": "The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis.", "contents": "Effects of nitric oxide synthase inhibitors on gastric alkaline secretion in rats. The effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on gastric HCO3- secretion were examined in anesthetized rats. Intravenous administration of L-NAME (1, 2.5, 5 mg/kg) increased HCO3- secretion in a dose-related manner. This effect of L-NAME was mimicked by NG-mono-methyl-L-arginine (50 mg/kg, i.v.) and was antagonized significantly by concurrent administration of L-arginine but not D-arginine (200 mg/kg, i.v.). These results indicate that gastric HCO3- secretion is stimulated by inhibition of NO biosynthesis."} {"id": "PMID:1283425", "title": "End-organ disease in hypertension: what have we learned?", "content": "The major target organs that suffer from sustained hypertension are the heart, kidneys, and brain. Cardiac adaptation to arterial hypertension consists of left ventricular hypertrophy (LVH) of the concentric type, that is, an increase in wall thickness at the expense of chamber volume. However, LVH can no longer be considered a simple adaptive myocardial process serving to compensate for the increase in afterload and bring left ventricular wall stress back to normal. Data from the Framingham cohort have shown that the occurrence of LVH drastically increases the risk of sudden death and other cardiovascular morbidity and mortality irrespective of the levels of arterial pressure. Renal adaptation to arterial hypertension consists of a decrease in renal blood flow with elevations in filtration fraction and renal vascular resistance. With progressive hypertensive cardiovascular disease, glomerular filtration rate will fall as well. Recent data in patients with mild-to-moderate hypertension demonstrate that despite \"efficacious\" antihypertensive therapy, one-third to one-half of hypertensive patients may experience a significant decline in renal function. Cerebrovascular adaptation to hypertension consists of micro- and macrovascular disease leading to vascular dementia, or ischemic or hemorrhagic stroke. Cerebrovascular autoregulation, the mechanism by which cerebral blood flow is maintained, despite changes in arterial pressure, may be altered in hypertension.", "contents": "End-organ disease in hypertension: what have we learned? The major target organs that suffer from sustained hypertension are the heart, kidneys, and brain. Cardiac adaptation to arterial hypertension consists of left ventricular hypertrophy (LVH) of the concentric type, that is, an increase in wall thickness at the expense of chamber volume. However, LVH can no longer be considered a simple adaptive myocardial process serving to compensate for the increase in afterload and bring left ventricular wall stress back to normal. Data from the Framingham cohort have shown that the occurrence of LVH drastically increases the risk of sudden death and other cardiovascular morbidity and mortality irrespective of the levels of arterial pressure. Renal adaptation to arterial hypertension consists of a decrease in renal blood flow with elevations in filtration fraction and renal vascular resistance. With progressive hypertensive cardiovascular disease, glomerular filtration rate will fall as well. Recent data in patients with mild-to-moderate hypertension demonstrate that despite \"efficacious\" antihypertensive therapy, one-third to one-half of hypertensive patients may experience a significant decline in renal function. Cerebrovascular adaptation to hypertension consists of micro- and macrovascular disease leading to vascular dementia, or ischemic or hemorrhagic stroke. Cerebrovascular autoregulation, the mechanism by which cerebral blood flow is maintained, despite changes in arterial pressure, may be altered in hypertension."} {"id": "PMID:1283426", "title": "Kinetics of angiotensin-converting enzyme inhibitors in renal failure.", "content": "Although there is impressive documentation linking severe hypertension to renal insufficiency, corresponding data for mild-to-moderate hypertension are only now starting to emerge. As a result, it is only now becoming evident that a much larger portion of the hypertensive population could be susceptible to drug accumulation owing to renal insufficiency. Angiotensin-converting enzyme (ACE) inhibitor therapy routinely requires dosage adjustment in the instance of renal insufficiency, as all currently marketed ACE inhibitors are renally eliminated. Such dosage adjustments are usually considered a way to minimize side effects and to limit the duration of any induced hypotension. Dosage adjustment is usually considered at creatinine clearance levels between 30 and 60 ml/min. This is somewhat problematic, as physicians generally rely on serum creatinine determinations to assess renal function, and serum creatinine values are notoriously poor predictors of actual creatinine clearance. This is particularly true in the elderly population, where a greater disparity between the serum creatinine and creatinine clearance commonly exists, with moderate renal insufficiency frequently going unrecognized. Thus, the development of other ACE inhibitors eliminated via renal/hepatic routes may prove to be advantageous in that dosage adjustments might not be required in the setting of declining renal function, whether age-related or not. Fosinopril, a new phosphorus-containing ACE inhibitor, is administered as a prodrug and is hydrolyzed to the pharmacologically active diacid, fosinoprilat.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Kinetics of angiotensin-converting enzyme inhibitors in renal failure. Although there is impressive documentation linking severe hypertension to renal insufficiency, corresponding data for mild-to-moderate hypertension are only now starting to emerge. As a result, it is only now becoming evident that a much larger portion of the hypertensive population could be susceptible to drug accumulation owing to renal insufficiency. Angiotensin-converting enzyme (ACE) inhibitor therapy routinely requires dosage adjustment in the instance of renal insufficiency, as all currently marketed ACE inhibitors are renally eliminated. Such dosage adjustments are usually considered a way to minimize side effects and to limit the duration of any induced hypotension. Dosage adjustment is usually considered at creatinine clearance levels between 30 and 60 ml/min. This is somewhat problematic, as physicians generally rely on serum creatinine determinations to assess renal function, and serum creatinine values are notoriously poor predictors of actual creatinine clearance. This is particularly true in the elderly population, where a greater disparity between the serum creatinine and creatinine clearance commonly exists, with moderate renal insufficiency frequently going unrecognized. Thus, the development of other ACE inhibitors eliminated via renal/hepatic routes may prove to be advantageous in that dosage adjustments might not be required in the setting of declining renal function, whether age-related or not. Fosinopril, a new phosphorus-containing ACE inhibitor, is administered as a prodrug and is hydrolyzed to the pharmacologically active diacid, fosinoprilat.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283427", "title": "Left ventricular hypertrophy and performance: therapeutic options among the angiotensin-converting enzyme inhibitors.", "content": "The goal of antihypertensive therapy is the reduction in morbidity and mortality associated with high blood pressure. Despite our ability to reduce blood pressure, \"standard\" antihypertensive therapy has not produced a general decrease in coronary heart disease. This failure might be related to the adverse metabolic consequences of diuretics and beta-adrenergic receptor-blocking agents used in most clinical trials. In the hypertensive patient population, however, the principal physiologic abnormality is increased systemic vascular resistance. This increase in vascular tone leads to compensatory changes in cardiac function that result in left ventricular hypertrophy and diastolic filling abnormalities. Diastolic ventricular dysfunction is present in approximately 50% of asymptomatic hypertensive patients and might be a precursor of the syndrome of congestive heart failure with normal systolic ventricular function. In view of the prevalence of diastolic filling abnormalities in the hypertensive patient population, one should consider the effect of an antihypertensive drug on left ventricular function. In a comparison of the angiotensin-converting enzyme (ACE) inhibitors, captopril, lisinopril, and fosinopril, only fosinopril increased stroke volume, peak ejection rate, and peak filling rate, and decreased time to peak ejection rate. These favorable inotropic and lusitropic responses to fosinopril may reflect an effect on the myocardial renin-angiotensin cascade which is dependent upon the unique chemical structure of the fosinopril molecule.", "contents": "Left ventricular hypertrophy and performance: therapeutic options among the angiotensin-converting enzyme inhibitors. The goal of antihypertensive therapy is the reduction in morbidity and mortality associated with high blood pressure. Despite our ability to reduce blood pressure, \"standard\" antihypertensive therapy has not produced a general decrease in coronary heart disease. This failure might be related to the adverse metabolic consequences of diuretics and beta-adrenergic receptor-blocking agents used in most clinical trials. In the hypertensive patient population, however, the principal physiologic abnormality is increased systemic vascular resistance. This increase in vascular tone leads to compensatory changes in cardiac function that result in left ventricular hypertrophy and diastolic filling abnormalities. Diastolic ventricular dysfunction is present in approximately 50% of asymptomatic hypertensive patients and might be a precursor of the syndrome of congestive heart failure with normal systolic ventricular function. In view of the prevalence of diastolic filling abnormalities in the hypertensive patient population, one should consider the effect of an antihypertensive drug on left ventricular function. In a comparison of the angiotensin-converting enzyme (ACE) inhibitors, captopril, lisinopril, and fosinopril, only fosinopril increased stroke volume, peak ejection rate, and peak filling rate, and decreased time to peak ejection rate. These favorable inotropic and lusitropic responses to fosinopril may reflect an effect on the myocardial renin-angiotensin cascade which is dependent upon the unique chemical structure of the fosinopril molecule."} {"id": "PMID:1283428", "title": "Treatment of hypertension: the place of angiotensin-converting enzyme inhibitors in the nineties.", "content": "The past decade has seen a shift in the strategy for hypertension treatment from stepped therapy--a highly structured monolithic series of steps--to recommendations for a more individualized selection of treatment. Severe hypertension is a clear indicator to bypass traditional steps. Demographic factors, such as age, gender, and race, are often cited, but have proved to be less helpful. Concomitant medical conditions and problems are very common and are more often the crucial determinants in the selection of antihypertensive therapy. Coronary artery disease, diabetes mellitus, heart failure, azotemia, asthma, and chronic obstructive pulmonary artery disease, anxiety, and depression are all common, and each has implications for the selection of antihypertensive therapy. Blood pressure reduction is a surrogate for reduction of cardiovascular risk, and therefore, consideration of concomitant medical problems has extended to left ventricular hypertrophy, obesity, mild hyperlipidemia, and insulin resistance, as additional risk factors in hypertension. Consideration of all these factors makes it possible to individualize antihypertensive therapy in most patients today.", "contents": "Treatment of hypertension: the place of angiotensin-converting enzyme inhibitors in the nineties. The past decade has seen a shift in the strategy for hypertension treatment from stepped therapy--a highly structured monolithic series of steps--to recommendations for a more individualized selection of treatment. Severe hypertension is a clear indicator to bypass traditional steps. Demographic factors, such as age, gender, and race, are often cited, but have proved to be less helpful. Concomitant medical conditions and problems are very common and are more often the crucial determinants in the selection of antihypertensive therapy. Coronary artery disease, diabetes mellitus, heart failure, azotemia, asthma, and chronic obstructive pulmonary artery disease, anxiety, and depression are all common, and each has implications for the selection of antihypertensive therapy. Blood pressure reduction is a surrogate for reduction of cardiovascular risk, and therefore, consideration of concomitant medical problems has extended to left ventricular hypertrophy, obesity, mild hyperlipidemia, and insulin resistance, as additional risk factors in hypertension. Consideration of all these factors makes it possible to individualize antihypertensive therapy in most patients today."} {"id": "PMID:1283429", "title": "Fosinopril: a new generation of angiotensin-converting enzyme inhibitors.", "content": "Fosinopril, the first agent in a new chemical class of phosphorus-containing angiotensin-converting enzyme (ACE) inhibitors, has unique pharmacologic properties. Fosinopril administration leads to complete inhibition of plasma ACE activity for 12-24 h. In patients with normal renal function, approximately equal amounts of the drug are eliminated via the hepatic and renal routes. With worsening renal function, increasing amounts of fosinopril are eliminated hepatically. This dual elimination allows for the administration of fosinopril using the same starting dosage to any patient, regardless of renal function. Fosinopril may provide end-organ protection against the effects of hypertension and antihypertensive therapy; this drug potentially protects the kidney by increasing renal functional reserve, while maintaining cardiac left ventricular performance. Moreover, despite marked blood reductions, cerebral blood flow is maintained. Controlled trials show that fosinopril in single daily doses of 10-40 mg is efficacious and safe for the long-term treatment of hypertension. At these doses, favorable responses were seen in up to 80% of patients. Fosinopril is equally effective in elderly as well as younger patients and works in black as well as in nonblack patients. The incidence of adverse events does not differ significantly between fosinopril- and placebo-treated patients. Fosinopril represents a clinically useful agent for the treatment of hypertension.", "contents": "Fosinopril: a new generation of angiotensin-converting enzyme inhibitors. Fosinopril, the first agent in a new chemical class of phosphorus-containing angiotensin-converting enzyme (ACE) inhibitors, has unique pharmacologic properties. Fosinopril administration leads to complete inhibition of plasma ACE activity for 12-24 h. In patients with normal renal function, approximately equal amounts of the drug are eliminated via the hepatic and renal routes. With worsening renal function, increasing amounts of fosinopril are eliminated hepatically. This dual elimination allows for the administration of fosinopril using the same starting dosage to any patient, regardless of renal function. Fosinopril may provide end-organ protection against the effects of hypertension and antihypertensive therapy; this drug potentially protects the kidney by increasing renal functional reserve, while maintaining cardiac left ventricular performance. Moreover, despite marked blood reductions, cerebral blood flow is maintained. Controlled trials show that fosinopril in single daily doses of 10-40 mg is efficacious and safe for the long-term treatment of hypertension. At these doses, favorable responses were seen in up to 80% of patients. Fosinopril is equally effective in elderly as well as younger patients and works in black as well as in nonblack patients. The incidence of adverse events does not differ significantly between fosinopril- and placebo-treated patients. Fosinopril represents a clinically useful agent for the treatment of hypertension."} {"id": "PMID:1283430", "title": "Quadruple labeling of brain-stem neurons: a multiple retrograde fluorescent tracer study of axonal collateralization.", "content": "Four different fluorochromes were injected into adjacent cervical spinal cord segments, 1 unique tracer per segment. Each tracer, Fluoro-Gold, Fast Blue, Diamidino Yellow dihydrochloride and Propidium Iodide, was taken up by axonal terminals and transported intra-axonally in a retrograde direction to the cell bodies. Some, though by no means all, of these axons were stem axons with terminals in 2, 3 or 4 of the injected spinal segments. Hence as many as 4 different fluorescent tracers could be discerned simultaneously within individual neuronal somata of origin using fluorescent microscopy. These results extend the possibilities for multiple interconnection determinations within the central nervous system. Specifically, the potential for individual neurons of a nucleus to project collateral branches of a stem axon to as many as 4 different central nervous system nuclei now can be studied simultaneously using these 4 fluorescent tracers.", "contents": "Quadruple labeling of brain-stem neurons: a multiple retrograde fluorescent tracer study of axonal collateralization. Four different fluorochromes were injected into adjacent cervical spinal cord segments, 1 unique tracer per segment. Each tracer, Fluoro-Gold, Fast Blue, Diamidino Yellow dihydrochloride and Propidium Iodide, was taken up by axonal terminals and transported intra-axonally in a retrograde direction to the cell bodies. Some, though by no means all, of these axons were stem axons with terminals in 2, 3 or 4 of the injected spinal segments. Hence as many as 4 different fluorescent tracers could be discerned simultaneously within individual neuronal somata of origin using fluorescent microscopy. These results extend the possibilities for multiple interconnection determinations within the central nervous system. Specifically, the potential for individual neurons of a nucleus to project collateral branches of a stem axon to as many as 4 different central nervous system nuclei now can be studied simultaneously using these 4 fluorescent tracers."} {"id": "PMID:1283431", "title": "Notes on a light and electron microscopic double-labeling method combining anterograde tracing with Phaseolus vulgaris leucoagglutinin and retrograde tracing with cholera toxin subunit B.", "content": "Investigations of monosynaptic connections in the central nervous system have been hindered by the lack of compatible markers that can be used at both light and electron microscopic levels. In attempts to determine synaptic contacts between fibers originating in the substantia nigra and neurons projecting to the spinal cord, we have developed a double immunolabeling technique using anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde transport of unconjugated cholera toxin subunit B (CTB). In this report, we describe technical modifications which consistently produced superior labeling together with adequate ultrastructural preservation of the tissue and discuss the advantages of the two tracers.", "contents": "Notes on a light and electron microscopic double-labeling method combining anterograde tracing with Phaseolus vulgaris leucoagglutinin and retrograde tracing with cholera toxin subunit B. Investigations of monosynaptic connections in the central nervous system have been hindered by the lack of compatible markers that can be used at both light and electron microscopic levels. In attempts to determine synaptic contacts between fibers originating in the substantia nigra and neurons projecting to the spinal cord, we have developed a double immunolabeling technique using anterograde transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde transport of unconjugated cholera toxin subunit B (CTB). In this report, we describe technical modifications which consistently produced superior labeling together with adequate ultrastructural preservation of the tissue and discuss the advantages of the two tracers."} {"id": "PMID:1283432", "title": "Biotin-dextran: a sensitive anterograde tracer for neuroanatomic studies in rat and monkey.", "content": "The properties of a new anterograde tracer, biotin-dextran (BD), are reported. Iontophoretic or pressure injections of BD in the spinal cord of rats and monkeys revealed terminal-like BD label in many regions of the brain. The BD label was visualized by an avidin-biotin reaction combined with diaminobenzidine, with and without nickel enhancement. This reaction resulted in permanent label and revealed the fine morphology of terminal boutons and en-passant endings. Biotin-dextran is an excellent anterograde tracer that can also be visualized at the electron microscopic level, used in combination with other retrograde and anterograde tracers and with immunohistochemical labeling of neurotransmitters.", "contents": "Biotin-dextran: a sensitive anterograde tracer for neuroanatomic studies in rat and monkey. The properties of a new anterograde tracer, biotin-dextran (BD), are reported. Iontophoretic or pressure injections of BD in the spinal cord of rats and monkeys revealed terminal-like BD label in many regions of the brain. The BD label was visualized by an avidin-biotin reaction combined with diaminobenzidine, with and without nickel enhancement. This reaction resulted in permanent label and revealed the fine morphology of terminal boutons and en-passant endings. Biotin-dextran is an excellent anterograde tracer that can also be visualized at the electron microscopic level, used in combination with other retrograde and anterograde tracers and with immunohistochemical labeling of neurotransmitters."} {"id": "PMID:1283433", "title": "Ca2+ currents of fast blue-labeled superior cervical ganglion neurons.", "content": "To investigate if Ca2+ currents of acutely isolated superior cervical ganglion (SCG) neurons are altered after dye labeling or ultraviolet (UV) exposure, SCG neurons were labeled by multiple injections of 2% fast blue (FB) (5-microliters total) into the submaxillary gland. Ca2+ currents of both labeled and unlabeled neurons were significantly depressed by 2-min exposure to UV, compared to labeled and unlabeled neurons not exposed to UV. The I-V curve of labeled neurons was shifted hyperpolarized after UV exposure. Tail-current activation curves of both labeled and unlabeled neurons were fitted to a double Boltzmann equation. In labeled neurons, 2-min exposure to UV produced a significant reduction of the amplitude of the more depolarized component as well as a hyperpolarizing shift of the half activation potential of both components of the activation curve. However, the short time (< 10 s) required to identify a target-specific neuron had no significant effect on the biophysical properties of Ca2+ currents of FB-labeled SCG neurons. Thus, use of this label in combination with the patch-clamp technique comprises a powerful approach to study membrane currents of target-specific neurons.", "contents": "Ca2+ currents of fast blue-labeled superior cervical ganglion neurons. To investigate if Ca2+ currents of acutely isolated superior cervical ganglion (SCG) neurons are altered after dye labeling or ultraviolet (UV) exposure, SCG neurons were labeled by multiple injections of 2% fast blue (FB) (5-microliters total) into the submaxillary gland. Ca2+ currents of both labeled and unlabeled neurons were significantly depressed by 2-min exposure to UV, compared to labeled and unlabeled neurons not exposed to UV. The I-V curve of labeled neurons was shifted hyperpolarized after UV exposure. Tail-current activation curves of both labeled and unlabeled neurons were fitted to a double Boltzmann equation. In labeled neurons, 2-min exposure to UV produced a significant reduction of the amplitude of the more depolarized component as well as a hyperpolarizing shift of the half activation potential of both components of the activation curve. However, the short time (< 10 s) required to identify a target-specific neuron had no significant effect on the biophysical properties of Ca2+ currents of FB-labeled SCG neurons. Thus, use of this label in combination with the patch-clamp technique comprises a powerful approach to study membrane currents of target-specific neurons."} {"id": "PMID:1283434", "title": "Intra-axonal Neurobiotin injection rapidly stains the long-range projections of identified trigeminal primary afferents in vivo: comparisons with HRP and PHA-L.", "content": "Currently available methods for studying the morphology of physiologically characterized primary afferents are limited by difficulties inherent in impaling thin fibers and by the limited distances over which conventional tracers move during the course of a recording session. We have encountered an alternative method that overcomes these limitations. Neurobiotin (NB; Vector) injections into rat trigeminal (V) primary afferents in the brain stem or V ganglion provided rapid, long-range staining with recording and electrophoretic parameters that are commonly used to eject horseradish peroxidase (HRP) or Phaseolus vulgaris leucoagglutinin (PHA-L). When NB was injected into brain stem fibers responsive to vibrissal deflection with A-beta conduction velocities, collaterals were darkly stained in each of the 4 V subnuclei, as well as the cervical dorsal horn. Labeled fibers were also seen in the V root and peripherally in the infra-orbital nerve for a distance up to 15 mm from the injection site (30 mm total). Cell bodies in the ganglion were never labeled. When NB was injected into V ganglion cells with low- or high-threshold receptive fields and A-beta or A-delta conduction velocities, parent axons were stained in the V spinal tract to the level of the obex, and collaterals were visible in each of the 4 V subnuclei. Such long-range staining occurred within 4 h of tracer injection. HRP never stained brain stem fibers following ganglion cell injections and, when injected centrally with the same survival intervals used with NB, dark staining was limited to within 4 mm of the injection site. Unlike NB or HRP, PHA-L injections rarely produced useful data, either because of the high mortality accompanying attempts to achieve a 1-2 week survival period or because injected neurons were not recovered. Due to its rapid and robust transport, NB is a more convenient and reliable tracer than PHA-L for producing long-range staining of the projections of identified ganglion cells. Intracellular injection of NB also produces rapid Golgi-like staining of fibers over much greater distances than HRP under equivalent staining parameters.", "contents": "Intra-axonal Neurobiotin injection rapidly stains the long-range projections of identified trigeminal primary afferents in vivo: comparisons with HRP and PHA-L. Currently available methods for studying the morphology of physiologically characterized primary afferents are limited by difficulties inherent in impaling thin fibers and by the limited distances over which conventional tracers move during the course of a recording session. We have encountered an alternative method that overcomes these limitations. Neurobiotin (NB; Vector) injections into rat trigeminal (V) primary afferents in the brain stem or V ganglion provided rapid, long-range staining with recording and electrophoretic parameters that are commonly used to eject horseradish peroxidase (HRP) or Phaseolus vulgaris leucoagglutinin (PHA-L). When NB was injected into brain stem fibers responsive to vibrissal deflection with A-beta conduction velocities, collaterals were darkly stained in each of the 4 V subnuclei, as well as the cervical dorsal horn. Labeled fibers were also seen in the V root and peripherally in the infra-orbital nerve for a distance up to 15 mm from the injection site (30 mm total). Cell bodies in the ganglion were never labeled. When NB was injected into V ganglion cells with low- or high-threshold receptive fields and A-beta or A-delta conduction velocities, parent axons were stained in the V spinal tract to the level of the obex, and collaterals were visible in each of the 4 V subnuclei. Such long-range staining occurred within 4 h of tracer injection. HRP never stained brain stem fibers following ganglion cell injections and, when injected centrally with the same survival intervals used with NB, dark staining was limited to within 4 mm of the injection site. Unlike NB or HRP, PHA-L injections rarely produced useful data, either because of the high mortality accompanying attempts to achieve a 1-2 week survival period or because injected neurons were not recovered. Due to its rapid and robust transport, NB is a more convenient and reliable tracer than PHA-L for producing long-range staining of the projections of identified ganglion cells. Intracellular injection of NB also produces rapid Golgi-like staining of fibers over much greater distances than HRP under equivalent staining parameters."} {"id": "PMID:1283437", "title": "Comparison of Borrelia burgdorferi isolated from humans and ixodid ticks in Hokkaido, Japan.", "content": "Four spirochetal isolates (JEM1 to JEM4) were obtained from cutaneous lesions of patients manifesting erythema chronicum migrans in Hokkaido, Japan. In the protein profiles by SDS-PAGE and the reactivities with monoclonal antibodies (H5332 and H9724) by immunoblotting, all the human isolates were identical with the tick isolates from Ixodes persulcatus. These data indicate that I. persulcatus is an important vector of Lyme disease for humans in Japan.", "contents": "Comparison of Borrelia burgdorferi isolated from humans and ixodid ticks in Hokkaido, Japan. Four spirochetal isolates (JEM1 to JEM4) were obtained from cutaneous lesions of patients manifesting erythema chronicum migrans in Hokkaido, Japan. In the protein profiles by SDS-PAGE and the reactivities with monoclonal antibodies (H5332 and H9724) by immunoblotting, all the human isolates were identical with the tick isolates from Ixodes persulcatus. These data indicate that I. persulcatus is an important vector of Lyme disease for humans in Japan."} {"id": "PMID:1283435", "title": "Electron microscopic analysis of fluorescent neuronal labeling after photoconversion.", "content": "Ultrastructural visualization of non-electron-dense fluorescent retrograde neuronal labeling was attempted by means of photo-oxidation. This procedure was used to convert the fluorescence of neurons labeled by the tracers propidium iodide, rhodamine latex microspheres and fluorogold into a stable diaminobenzidine reaction product. The ultrastructural study revealed an accumulation of electron-dense material in these cells both within lysosomes and scattered in the cytoplasmic matrix. Comparison with several different sets of control samples indicated that this material, on the basis of its amount, electron density and appearance, specifically represents the photoconversion reaction product. The effects of the intensity of the fluorescent labeling and of a prolonged photoconversion on the fine structural features of the reaction product are also described and discussed. The present findings indicate that photoconversion can be effectively applied to ultrastructural study of fluorescent retrogradely labeled neurons. The specificity of the photoconversion reaction product should be tested routinely for each fluorochrome and tissue sample.", "contents": "Electron microscopic analysis of fluorescent neuronal labeling after photoconversion. Ultrastructural visualization of non-electron-dense fluorescent retrograde neuronal labeling was attempted by means of photo-oxidation. This procedure was used to convert the fluorescence of neurons labeled by the tracers propidium iodide, rhodamine latex microspheres and fluorogold into a stable diaminobenzidine reaction product. The ultrastructural study revealed an accumulation of electron-dense material in these cells both within lysosomes and scattered in the cytoplasmic matrix. Comparison with several different sets of control samples indicated that this material, on the basis of its amount, electron density and appearance, specifically represents the photoconversion reaction product. The effects of the intensity of the fluorescent labeling and of a prolonged photoconversion on the fine structural features of the reaction product are also described and discussed. The present findings indicate that photoconversion can be effectively applied to ultrastructural study of fluorescent retrogradely labeled neurons. The specificity of the photoconversion reaction product should be tested routinely for each fluorochrome and tissue sample."} {"id": "PMID:1283438", "title": "Serological cross-reaction between intact and chemically modified lipopolysaccharides of O1 Vibrio cholerae Inaba and non-O1 V. cholerae bio-serogroup Hakata.", "content": "Serological cross-reaction of intact as well as chemically modified LPS from O1 Vibrio cholerae 569B (Inaba) with non-O1 V. cholerae Hakata LPS, which contain alpha(1-->2)-linked N-acetyl perosamine-homopolymer constituting their O polysaccharide chain, was studied by passive hemolysis test by using their LPS as antigen for sensitizing sheep red blood cells (SRBC). The N-deacylation of the alpha(1-->2)-linked linear 3-deoxy-tetronyl perosamine-homopolymer constituting the O polysaccharide chain in 569B LPS resulted in virtual elimination of their serological reactivity with both homologous Inaba and heterologous Hakata antisera. Furthermore, when the resultant NH2 groups of the N-deacylated perosamine-homopolymers in 569B LPS were N-acylated with acetyl, propionyl or butanoyl groups, they markedly recovered the serological reactivity to a marked extent, in particular, their pronounced cross-serological reactivity with heterologous Hakata antiserum. These results are believed to be compatible with the interpretation that the Inaba antigen factor C possessed by the two bacteria studied is related to the common occurrence of the N-acyl groups, regardless of what the acyl groups are, residing in the perosamine residues of the perosamine-homopolymers constituting the O polysaccharide chain of their LPS.", "contents": "Serological cross-reaction between intact and chemically modified lipopolysaccharides of O1 Vibrio cholerae Inaba and non-O1 V. cholerae bio-serogroup Hakata. Serological cross-reaction of intact as well as chemically modified LPS from O1 Vibrio cholerae 569B (Inaba) with non-O1 V. cholerae Hakata LPS, which contain alpha(1-->2)-linked N-acetyl perosamine-homopolymer constituting their O polysaccharide chain, was studied by passive hemolysis test by using their LPS as antigen for sensitizing sheep red blood cells (SRBC). The N-deacylation of the alpha(1-->2)-linked linear 3-deoxy-tetronyl perosamine-homopolymer constituting the O polysaccharide chain in 569B LPS resulted in virtual elimination of their serological reactivity with both homologous Inaba and heterologous Hakata antisera. Furthermore, when the resultant NH2 groups of the N-deacylated perosamine-homopolymers in 569B LPS were N-acylated with acetyl, propionyl or butanoyl groups, they markedly recovered the serological reactivity to a marked extent, in particular, their pronounced cross-serological reactivity with heterologous Hakata antiserum. These results are believed to be compatible with the interpretation that the Inaba antigen factor C possessed by the two bacteria studied is related to the common occurrence of the N-acyl groups, regardless of what the acyl groups are, residing in the perosamine residues of the perosamine-homopolymers constituting the O polysaccharide chain of their LPS."} {"id": "PMID:1283436", "title": "Staining myelin and myelin-like degradation products in the spinal cords of chronic experimental allergic encephalomyelitis (Cr-EAE) rats using Sudan black B staining of glycol methacrylate-embedded material.", "content": "A high-resolution light-microscopical (HRLM) technique is described to visualize myelin, and macrophages containing degradation products of myelin, in the spinal cords of chronic relapsing experimental allergic encephalomyelitis (Cr-EAE) rats. This HRLM technique was developed to optimalize the correlation between nuclear magnetic resonance (NMR) characteristics and histopathological images in this well-established animal model for multiple sclerosis (MS). Spinal cords were fixed by perfusion with a combination of cacodylate-buffered glutaraldehyde and formaldehyde, post-fixed in Dalton's fixative (containing osmium tetroxide), rinsed in water, processed in ethanol, acetone, and embedded in glycol methacrylate resin (Technovit 7100/HistoResin). Semi-thin sections were stained with Sudan Black B and counterstained with Cresyl Fast Violet, resulting in black staining of myelin and its degradation products, with blue/violet staining of demyelinated axons and other tissue elements. These dyes were selected with the aid of a numerical model of staining, which took both access and lipophilicity into account. The staining procedure is simple and highly reproducible. The resulting images are contrast rich, and combine excellent morphology with a high degree of lipid retention.", "contents": "Staining myelin and myelin-like degradation products in the spinal cords of chronic experimental allergic encephalomyelitis (Cr-EAE) rats using Sudan black B staining of glycol methacrylate-embedded material. A high-resolution light-microscopical (HRLM) technique is described to visualize myelin, and macrophages containing degradation products of myelin, in the spinal cords of chronic relapsing experimental allergic encephalomyelitis (Cr-EAE) rats. This HRLM technique was developed to optimalize the correlation between nuclear magnetic resonance (NMR) characteristics and histopathological images in this well-established animal model for multiple sclerosis (MS). Spinal cords were fixed by perfusion with a combination of cacodylate-buffered glutaraldehyde and formaldehyde, post-fixed in Dalton's fixative (containing osmium tetroxide), rinsed in water, processed in ethanol, acetone, and embedded in glycol methacrylate resin (Technovit 7100/HistoResin). Semi-thin sections were stained with Sudan Black B and counterstained with Cresyl Fast Violet, resulting in black staining of myelin and its degradation products, with blue/violet staining of demyelinated axons and other tissue elements. These dyes were selected with the aid of a numerical model of staining, which took both access and lipophilicity into account. The staining procedure is simple and highly reproducible. The resulting images are contrast rich, and combine excellent morphology with a high degree of lipid retention."} {"id": "PMID:1283440", "title": "Hepatitis C: an update.", "content": "The identification of the Hepatitis C virus using molecular cloning techniques, besides making the term Non-A Non-B Hepatitis obsolete, enables the development of specific assays for the detection of antibodies in HCV-infected individuals, thus making it possible to obtain sero-epidemiological data of the disease. The carriage of Hepatitis C antibody varies worldwide. The disease is most prevalent in intravenous drug abusers or haemophiliacs. Parenteral transmission is the most important route of transmission. Sexual, intra-familial and perinatal transmissions are uncommon. About 40% could be community-acquired (sporadic). Diagnostic tests include enzyme-linked immunosorbant (ELISA) anti-HCV assay, recombinant immunoblot assay, HCV-RNA by polymerase chain reaction and HCV-Ag. More than 50% of acute cases becomes chronic and runs a benign and indolent course. About 20% progress to cirrhosis and some of these develop hepatocellular carcinoma. Several published trials have consistently shown that treatment with interferon in some patients is useful. There is however a relapse rate of 50%. Further trials with interferon and other anti-viral agents like ribavirin are awaited for more effective treatment.", "contents": "Hepatitis C: an update. The identification of the Hepatitis C virus using molecular cloning techniques, besides making the term Non-A Non-B Hepatitis obsolete, enables the development of specific assays for the detection of antibodies in HCV-infected individuals, thus making it possible to obtain sero-epidemiological data of the disease. The carriage of Hepatitis C antibody varies worldwide. The disease is most prevalent in intravenous drug abusers or haemophiliacs. Parenteral transmission is the most important route of transmission. Sexual, intra-familial and perinatal transmissions are uncommon. About 40% could be community-acquired (sporadic). Diagnostic tests include enzyme-linked immunosorbant (ELISA) anti-HCV assay, recombinant immunoblot assay, HCV-RNA by polymerase chain reaction and HCV-Ag. More than 50% of acute cases becomes chronic and runs a benign and indolent course. About 20% progress to cirrhosis and some of these develop hepatocellular carcinoma. Several published trials have consistently shown that treatment with interferon in some patients is useful. There is however a relapse rate of 50%. Further trials with interferon and other anti-viral agents like ribavirin are awaited for more effective treatment."} {"id": "PMID:1283441", "title": "Retinoic acid receptor-beta: immunodetection and phosphorylation on tyrosine residues.", "content": "Polyclonal (RP) and monoclonal (Ab) antibodies were raised against synthetic peptides (or fusion proteins) corresponding to amino acid sequences unique to human and mouse retinoic acid receptor-beta (RAR beta) isoforms. Antibodies directed against the A2 region [Ab6 beta 2(A2), Ab7 beta 2(A2), and RP beta 2(A2)], the D2 region [RP beta(D2)], or the F region [Ab8 beta(F)2, RP beta(F)1, and RP beta(F)2] were selected. The monoclonal and polyclonal antibodies directed against the D2 and F regions specifically immunoprecipitated and recognized by Western blotting all human and mouse RAR beta isoforms (mRAR beta 1, -beta 2, -beta 3, and -beta 4), produced in COS-1 cells transfected with expression vectors containing the corresponding RAR beta cDNA. Furthermore, in gel retardation assays, the monoclonal antibodies supershifted RAR beta protein-RA response element oligonucleotide complexes. Antibodies directed against the A2 region were specific for the RAR beta 2 isoform. The above antibodies allowed us to detect the presence of mRAR beta 2 proteins in mouse embryos and to show that their presence in embryonal carcinoma cells (F9 and P19 cell lines) is dependent upon RA treatment. The antibodies were also used to demonstrate that RAR beta proteins produced by transfection in COS-1 cells are phosphorylated. RAR beta 2 phosphorylation was not affected by RA treatment, whereas the phosphorylation of RAR beta 1 and RAR beta 3 isoforms was greatly enhanced by RA. We also show that, in contrast to RAR alpha 1 and RAR gamma 1, RAR beta 2 proteins contain phosphotyrosine residues and are only weakly phosphorylated in vitro by cAMP-dependent protein kinase. These results support our previous proposal that the various receptors have distinct functions in the RA-signaling pathway.", "contents": "Retinoic acid receptor-beta: immunodetection and phosphorylation on tyrosine residues. Polyclonal (RP) and monoclonal (Ab) antibodies were raised against synthetic peptides (or fusion proteins) corresponding to amino acid sequences unique to human and mouse retinoic acid receptor-beta (RAR beta) isoforms. Antibodies directed against the A2 region [Ab6 beta 2(A2), Ab7 beta 2(A2), and RP beta 2(A2)], the D2 region [RP beta(D2)], or the F region [Ab8 beta(F)2, RP beta(F)1, and RP beta(F)2] were selected. The monoclonal and polyclonal antibodies directed against the D2 and F regions specifically immunoprecipitated and recognized by Western blotting all human and mouse RAR beta isoforms (mRAR beta 1, -beta 2, -beta 3, and -beta 4), produced in COS-1 cells transfected with expression vectors containing the corresponding RAR beta cDNA. Furthermore, in gel retardation assays, the monoclonal antibodies supershifted RAR beta protein-RA response element oligonucleotide complexes. Antibodies directed against the A2 region were specific for the RAR beta 2 isoform. The above antibodies allowed us to detect the presence of mRAR beta 2 proteins in mouse embryos and to show that their presence in embryonal carcinoma cells (F9 and P19 cell lines) is dependent upon RA treatment. The antibodies were also used to demonstrate that RAR beta proteins produced by transfection in COS-1 cells are phosphorylated. RAR beta 2 phosphorylation was not affected by RA treatment, whereas the phosphorylation of RAR beta 1 and RAR beta 3 isoforms was greatly enhanced by RA. We also show that, in contrast to RAR alpha 1 and RAR gamma 1, RAR beta 2 proteins contain phosphotyrosine residues and are only weakly phosphorylated in vitro by cAMP-dependent protein kinase. These results support our previous proposal that the various receptors have distinct functions in the RA-signaling pathway."} {"id": "PMID:1283442", "title": "Insulin rapidly decreases insulin-like growth factor-binding protein-1 gene transcription in streptozotocin-diabetic rats.", "content": "Insulin-like growth factor-binding protein-1 (IGFBP-1) can inhibit or potentiate IGF action. The biological activity of IGFBP-1 is determined by many factors, including its abundance in tissues and plasma, posttranslational modifications, and localization. IGFBP-1 levels in human plasma are highly regulated. They are increased after acute fasting and in diabetes, and are rapidly reversed by refeeding and insulin treatment, respectively. Similarly, IGFBP-1 mRNA is increased in the liver of severely diabetic and ketotic rats and decreased after 4 days of insulin treatment. Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells. The present study asks whether the increase in IGFBP-1 mRNA in diabetic rat liver reflects increased gene transcription, whether insulin decreases IGFBP-1 mRNA through a transcriptional or posttranscriptional mechanism, and whether this decrease is sufficiently rapid to account for the dynamic fluctuations in plasma IGFBP-1. Rats were injected ip with 100 mg/kg streptozotocin and used 7 days later when they were hyperglycemic and failed to gain weight, but were not ketotic. Hepatic IGFBP-1 mRNA levels were 13.6 +/- 5.3-fold greater in diabetic than control liver and decreased to the low levels in nondiabetic controls within 1 h after insulin treatment. In run-on transcription assays, IGFBP-1 transcription was 12.6 +/- 1.5-fold greater in nuclei from diabetic than control liver and decreased to low control levels by 1 h after insulin injection. Normalization of hepatic IGFBP-1 mRNA in insulin-treated diabetic animals did not require restoration of euglycemia. IGFBP-1 mRNA and IGFBP-1 gene transcription also were increased in the kidney of diabetic ketotic rats. We propose that the dynamic regulation of IGFBP-1 gene transcription in diabetes and after insulin treatment, by determining the availability of IGFBP-1 in tissues and plasma, may be a critical factor in the modulation of IGF action.", "contents": "Insulin rapidly decreases insulin-like growth factor-binding protein-1 gene transcription in streptozotocin-diabetic rats. Insulin-like growth factor-binding protein-1 (IGFBP-1) can inhibit or potentiate IGF action. The biological activity of IGFBP-1 is determined by many factors, including its abundance in tissues and plasma, posttranslational modifications, and localization. IGFBP-1 levels in human plasma are highly regulated. They are increased after acute fasting and in diabetes, and are rapidly reversed by refeeding and insulin treatment, respectively. Similarly, IGFBP-1 mRNA is increased in the liver of severely diabetic and ketotic rats and decreased after 4 days of insulin treatment. Insulin rapidly decreases IGFBP-1 mRNA and IGFBP-1 transcription in rat hepatoma cells. The present study asks whether the increase in IGFBP-1 mRNA in diabetic rat liver reflects increased gene transcription, whether insulin decreases IGFBP-1 mRNA through a transcriptional or posttranscriptional mechanism, and whether this decrease is sufficiently rapid to account for the dynamic fluctuations in plasma IGFBP-1. Rats were injected ip with 100 mg/kg streptozotocin and used 7 days later when they were hyperglycemic and failed to gain weight, but were not ketotic. Hepatic IGFBP-1 mRNA levels were 13.6 +/- 5.3-fold greater in diabetic than control liver and decreased to the low levels in nondiabetic controls within 1 h after insulin treatment. In run-on transcription assays, IGFBP-1 transcription was 12.6 +/- 1.5-fold greater in nuclei from diabetic than control liver and decreased to low control levels by 1 h after insulin injection. Normalization of hepatic IGFBP-1 mRNA in insulin-treated diabetic animals did not require restoration of euglycemia. IGFBP-1 mRNA and IGFBP-1 gene transcription also were increased in the kidney of diabetic ketotic rats. We propose that the dynamic regulation of IGFBP-1 gene transcription in diabetes and after insulin treatment, by determining the availability of IGFBP-1 in tissues and plasma, may be a critical factor in the modulation of IGF action."} {"id": "PMID:1283443", "title": "Monoclonal antibodies to two adhesive cell surface antigens (CD43 and CD59) with different distribution on hematopoietic and non-hematopoietic tumor cell lines.", "content": "Two new murine monoclonal antibodies were prepared by hybridoma technique after immunization with the immature pluripotent leukemia cell line K562. The monoclonal antibody Bra10G (IgG2b) reacted in a non-lineage pattern with all examined hematopoietic neoplastic cell lines and peripheral blood cells (granulocytes, lymphocytes, erythrocytes) of healthy donors, with the exception of monoblastoid cell line U-937 and B lymphoma cell line Daudi. This monoclonal antibody immunoprecipitated an 18-20 kDa cell surface protein expressed also on the cell surface of examined non-hematopoietic (malignant glioma, melanoma and breast carcinoma) cell lines. These properties and the efficient inhibition of Bra10G binding to the cell surface of K562 cells by the reference CD59 monoclonal antibody (MEM-43) indicated that Bra10G belongs to the CD59 cluster of monoclonal antibodies which identify the human protectin molecule. The monoclonal antibody Bra7G (IgM) reacted with a 95 kDa cell surface protein expressed on hematopoietic cells (with the exception of erythrocytes) and was absent on the examined non-hematopoietic neoplastic cell lines. These data together with a partial inhibition of Bra7G binding by the reference CD-43 monoclonal antibody suggested the CD43 (leukosialin, sialophorin) specificity of this monoclonal antibody.", "contents": "Monoclonal antibodies to two adhesive cell surface antigens (CD43 and CD59) with different distribution on hematopoietic and non-hematopoietic tumor cell lines. Two new murine monoclonal antibodies were prepared by hybridoma technique after immunization with the immature pluripotent leukemia cell line K562. The monoclonal antibody Bra10G (IgG2b) reacted in a non-lineage pattern with all examined hematopoietic neoplastic cell lines and peripheral blood cells (granulocytes, lymphocytes, erythrocytes) of healthy donors, with the exception of monoblastoid cell line U-937 and B lymphoma cell line Daudi. This monoclonal antibody immunoprecipitated an 18-20 kDa cell surface protein expressed also on the cell surface of examined non-hematopoietic (malignant glioma, melanoma and breast carcinoma) cell lines. These properties and the efficient inhibition of Bra10G binding to the cell surface of K562 cells by the reference CD59 monoclonal antibody (MEM-43) indicated that Bra10G belongs to the CD59 cluster of monoclonal antibodies which identify the human protectin molecule. The monoclonal antibody Bra7G (IgM) reacted with a 95 kDa cell surface protein expressed on hematopoietic cells (with the exception of erythrocytes) and was absent on the examined non-hematopoietic neoplastic cell lines. These data together with a partial inhibition of Bra7G binding by the reference CD-43 monoclonal antibody suggested the CD43 (leukosialin, sialophorin) specificity of this monoclonal antibody."} {"id": "PMID:1283444", "title": "Monitoring of patients with non-seminomatous germ cell tumors of the testis by determination of alpha-fetoprotein and beta-human chorionic gonadotropin levels and by computed tomography.", "content": "The results of a 7-year monitoring of 230 patients with non-seminomatous testicular tumors are reported with respect to the employment of radioimmunoanalysis of alpha-fetoprotein and beta-human chorionic gonadotropin levels and CT examinations of retroperitoneum and lungs. Prior to orchiectomy, elevated levels of at least one of these markers were found in 79% of patients. After orchiectomy, tumor marker levels were in 70.4% of patients in agreement with the results of CT examinations. After the completion of chemotherapy, in more than a half of patients normal tumor marker levels and positive CT findings were observed. These results were most often due to the presence of mature teratoma. In Stage I patients the advantages of tumor marker determinations and CT examinations in the early detection of tumor progression have fully been confirmed.", "contents": "Monitoring of patients with non-seminomatous germ cell tumors of the testis by determination of alpha-fetoprotein and beta-human chorionic gonadotropin levels and by computed tomography. The results of a 7-year monitoring of 230 patients with non-seminomatous testicular tumors are reported with respect to the employment of radioimmunoanalysis of alpha-fetoprotein and beta-human chorionic gonadotropin levels and CT examinations of retroperitoneum and lungs. Prior to orchiectomy, elevated levels of at least one of these markers were found in 79% of patients. After orchiectomy, tumor marker levels were in 70.4% of patients in agreement with the results of CT examinations. After the completion of chemotherapy, in more than a half of patients normal tumor marker levels and positive CT findings were observed. These results were most often due to the presence of mature teratoma. In Stage I patients the advantages of tumor marker determinations and CT examinations in the early detection of tumor progression have fully been confirmed."} {"id": "PMID:1283446", "title": "[Lactic acidosis, hyperamylasemia, and phenformin].", "content": "Phenformin is still used in the therapy of non-insulin dependent diabetes in association with sulphonylureas. The controindications to the use of this drug often are not kept in due consideration. It is therefore often possible to observe cases of irreversible lactic acidosis with lethal outcome. In this paper, three cases of lactic acidosis from phenformin administration are reported. Some characteristics of this clinical picture are underscored: accompanying ketoacidosis, hyperamylasemia. On the basis of their observation, the Authors conclude that those diabetic patients who can be treated with diet alone or with diet and sulphonylureas must not be treated with phenformin. Metformin is then proposed as a more flexible and safer drug.", "contents": "[Lactic acidosis, hyperamylasemia, and phenformin]. Phenformin is still used in the therapy of non-insulin dependent diabetes in association with sulphonylureas. The controindications to the use of this drug often are not kept in due consideration. It is therefore often possible to observe cases of irreversible lactic acidosis with lethal outcome. In this paper, three cases of lactic acidosis from phenformin administration are reported. Some characteristics of this clinical picture are underscored: accompanying ketoacidosis, hyperamylasemia. On the basis of their observation, the Authors conclude that those diabetic patients who can be treated with diet alone or with diet and sulphonylureas must not be treated with phenformin. Metformin is then proposed as a more flexible and safer drug."} {"id": "PMID:1283447", "title": "Prevalence of antibodies to hepatitis C in dialysis patients and transplant recipients with possible routes of transmission.", "content": "The prevalence of hepatitis C infection and possible predisposing factors was assessed in a renal unit. Of 343 patients at our renal dialysis centre, 37 (10.8%) were anti-HCV positive by a 1st-generation assay (ELISA, Ortho/Chiron) and confirmed positive in 35 (10.2%) with a 2nd-generation test (UBI, New York). Anti-HCV positivity was significantly associated with: duration of renal replacement therapy (P < 0.0001); quantity of blood transfused (P < 0.002); duration of hospital haemodialysis (P = 0.0001); duration with a functional renal transplant (P = 0.039); and aspartate aminotransferase (P < 0.0001). Logistic regression determined the following variables to be independent risk factors: duration of renal replacement therapy with a relative risk of 34.3 for 5-9 years and 87.4 when the duration was in excess of 10 years; renal transplant for less than 1 year (relative risk of 5.0); transfusion in excess of 50 units of blood (relative risk of 11.6). Clinical assessment of anti-HCV-positive patients revealed peripheral signs of chronic liver disease in 40%, hepatomegaly in 34%, and splenomegaly in 9%. This prevalence of hepatitis C infection is similar to other European and North American centres, but contrasts with low prevalence rates reported from dialysis populations in the UK. It adds further support for routine screening of blood and possibly organ donors and implementation of further infection control measures in dialysis centres.", "contents": "Prevalence of antibodies to hepatitis C in dialysis patients and transplant recipients with possible routes of transmission. The prevalence of hepatitis C infection and possible predisposing factors was assessed in a renal unit. Of 343 patients at our renal dialysis centre, 37 (10.8%) were anti-HCV positive by a 1st-generation assay (ELISA, Ortho/Chiron) and confirmed positive in 35 (10.2%) with a 2nd-generation test (UBI, New York). Anti-HCV positivity was significantly associated with: duration of renal replacement therapy (P < 0.0001); quantity of blood transfused (P < 0.002); duration of hospital haemodialysis (P = 0.0001); duration with a functional renal transplant (P = 0.039); and aspartate aminotransferase (P < 0.0001). Logistic regression determined the following variables to be independent risk factors: duration of renal replacement therapy with a relative risk of 34.3 for 5-9 years and 87.4 when the duration was in excess of 10 years; renal transplant for less than 1 year (relative risk of 5.0); transfusion in excess of 50 units of blood (relative risk of 11.6). Clinical assessment of anti-HCV-positive patients revealed peripheral signs of chronic liver disease in 40%, hepatomegaly in 34%, and splenomegaly in 9%. This prevalence of hepatitis C infection is similar to other European and North American centres, but contrasts with low prevalence rates reported from dialysis populations in the UK. It adds further support for routine screening of blood and possibly organ donors and implementation of further infection control measures in dialysis centres."} {"id": "PMID:1283445", "title": "Reduced GAP-43 message levels are associated with increased neurofibrillary tangle density in the frontal association cortex (area 9) in Alzheimer's disease.", "content": "We previously suggested the hypothesis that defective neuronal plasticity is a major neurobiological deficit causing the dementia of Alzheimer's disease (AD). We used message levels of the growth-associated protein, GAP-43, as a marker of axonal plasticity to examine the hypothesis of defective neuronal plasticity in AD. When all AD cases are combined, the average level of GAP-43 message in area 9 of the AD frontal association cortex was not significantly different from the level in the comparably aged control cortex. Differentiation of AD cases on the basis of neurofibrillary tangle (NFT) density revealed that in AD cases with high tangle density average GAP-43 message level was reduced fivefold relative to levels in AD cases with low NFT density. AD cases with low neurofibrillary tangle density had levels of GAP-43 message that were not significantly different from the levels of normal controls. Differentiation of AD cases on the basis of neuritic plaque density did not indicate as strong a relationship to GAP-43 message level. The association between neurofibrillary tangle density and GAP-43 message level suggests the hypothesis that neurofibrillary tangles may reduce GAP-43 expression. Data of others show a relationship between high NFT density and reduced levels of synaptophysin-like immunoreactivity and reduced cerebral glucose metabolism. These data combine to suggest a set of AD cases with high NFT density, reduced axonal plasticity, reduced synaptic density, and reduced cerebral glucose metabolism--all variables that may be directly related to the functioning of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)", "contents": "Reduced GAP-43 message levels are associated with increased neurofibrillary tangle density in the frontal association cortex (area 9) in Alzheimer's disease. We previously suggested the hypothesis that defective neuronal plasticity is a major neurobiological deficit causing the dementia of Alzheimer's disease (AD). We used message levels of the growth-associated protein, GAP-43, as a marker of axonal plasticity to examine the hypothesis of defective neuronal plasticity in AD. When all AD cases are combined, the average level of GAP-43 message in area 9 of the AD frontal association cortex was not significantly different from the level in the comparably aged control cortex. Differentiation of AD cases on the basis of neurofibrillary tangle (NFT) density revealed that in AD cases with high tangle density average GAP-43 message level was reduced fivefold relative to levels in AD cases with low NFT density. AD cases with low neurofibrillary tangle density had levels of GAP-43 message that were not significantly different from the levels of normal controls. Differentiation of AD cases on the basis of neuritic plaque density did not indicate as strong a relationship to GAP-43 message level. The association between neurofibrillary tangle density and GAP-43 message level suggests the hypothesis that neurofibrillary tangles may reduce GAP-43 expression. Data of others show a relationship between high NFT density and reduced levels of synaptophysin-like immunoreactivity and reduced cerebral glucose metabolism. These data combine to suggest a set of AD cases with high NFT density, reduced axonal plasticity, reduced synaptic density, and reduced cerebral glucose metabolism--all variables that may be directly related to the functioning of the brain.(ABSTRACT TRUNCATED AT 250 WORDS)"} {"id": "PMID:1283450", "title": "Localization of preprogalanin mRNA in the monkey hippocampal formation.", "content": "The existence of neurons expressing preprogalanin mRNA in the monkey hippocampal formation was demonstrated using in situ hybridization of a radio-labelled cRNA probe transcribed from human preprogalanin cDNA. Specific hybridization occurred in neurons of the hilus of the dentate gyrus, fields CA1-3 in Ammon's horn, subiculum, presubiculum, parasubiculum and occasionally in neurons of the entorhinal cortex. These findings suggest that galanin is synthesized by neurons intrinsic to the monkey hippocampal formation.", "contents": "Localization of preprogalanin mRNA in the monkey hippocampal formation. The existence of neurons expressing preprogalanin mRNA in the monkey hippocampal formation was demonstrated using in situ hybridization of a radio-labelled cRNA probe transcribed from human preprogalanin cDNA. Specific hybridization occurred in neurons of the hilus of the dentate gyrus, fields CA1-3 in Ammon's horn, subiculum, presubiculum, parasubiculum and occasionally in neurons of the entorhinal cortex. These findings suggest that galanin is synthesized by neurons intrinsic to the monkey hippocampal formation."} {"id": "PMID:1283451", "title": "Phase shifting of the circadian rhythm in the eye of Bulla by inhibition of chloride conductance.", "content": "Inhibition of Cl- conductance has been previously found to shorten the free-running period of the circadian eye rhythm of the marine snail Bulla gouldiana. In this study, we describe a phase-response curve for 6-h pulses of Cl(-)-free seawater, consisting only of phase advances with the largest in the late subjective night (1.5 h) and smaller phase shifts in the late subjective day. Intracellular recordings revealed that at both circadian times retinal pacemaker neurons hyperpolarized in response to the removal of extracellular chloride. Since previous studies indicate that membrane potential generates both phase advances and delays it seems unlikely that the action of chloride removal is mediated exclusively by the change in membrane potential.", "contents": "Phase shifting of the circadian rhythm in the eye of Bulla by inhibition of chloride conductance. Inhibition of Cl- conductance has been previously found to shorten the free-running period of the circadian eye rhythm of the marine snail Bulla gouldiana. In this study, we describe a phase-response curve for 6-h pulses of Cl(-)-free seawater, consisting only of phase advances with the largest in the late subjective night (1.5 h) and smaller phase shifts in the late subjective day. Intracellular recordings revealed that at both circadian times retinal pacemaker neurons hyperpolarized in response to the removal of extracellular chloride. Since previous studies indicate that membrane potential generates both phase advances and delays it seems unlikely that the action of chloride removal is mediated exclusively by the change in membrane potential."} {"id": "PMID:1283452", "title": "Activation of a metabotropic excitatory amino acid receptor potentiates A2b adenosine receptor-stimulated cyclic AMP accumulation.", "content": "Incubation of guinea-pig cerebral cortical slices with the excitatory amino acid agonists DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) or N-methyl-D-aspartate (NMDA) failed to significantly alter either basal or 5'-N-ethylcarboxamidoadenosine- (NECA-)stimulated cAMP levels. Quisqualate, L-glutamate and DL-1-aminocyclopentane-trans-1,3- dicarboxylate (t-ACPD) were also without effect on basal levels of cAMP but increased NECA-stimulated levels of cAMP to approximately 190, 220 and 290% of control levels, respectively. Analysis of t-ACPD concentration-response data for the potentiation of NECA-stimulated cAMP elevations and the stimulation of phosphoinositide turnover gave EC50 values of 51 and 107 microM, respectively. The enhancing effect of t-ACPD on cAMP levels was maintained for up to 40 minutes as was the stimulation of phosphoinositide turnover. We conclude that the cAMP response to A2b adenosine receptor stimulation is augmented by the rigid glutamate analogue t-ACPD, possibly through the action of products of phosphoinositide turnover.", "contents": "Activation of a metabotropic excitatory amino acid receptor potentiates A2b adenosine receptor-stimulated cyclic AMP accumulation. Incubation of guinea-pig cerebral cortical slices with the excitatory amino acid agonists DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) or N-methyl-D-aspartate (NMDA) failed to significantly alter either basal or 5'-N-ethylcarboxamidoadenosine- (NECA-)stimulated cAMP levels. Quisqualate, L-glutamate and DL-1-aminocyclopentane-trans-1,3- dicarboxylate (t-ACPD) were also without effect on basal levels of cAMP but increased NECA-stimulated levels of cAMP to approximately 190, 220 and 290% of control levels, respectively. Analysis of t-ACPD concentration-response data for the potentiation of NECA-stimulated cAMP elevations and the stimulation of phosphoinositide turnover gave EC50 values of 51 and 107 microM, respectively. The enhancing effect of t-ACPD on cAMP levels was maintained for up to 40 minutes as was the stimulation of phosphoinositide turnover. We conclude that the cAMP response to A2b adenosine receptor stimulation is augmented by the rigid glutamate analogue t-ACPD, possibly through the action of products of phosphoinositide turnover."} {"id": "PMID:1283453", "title": "m4 muscarinic receptor subtype activates an inwardly rectifying potassium conductance in AtT20 cells.", "content": "The modulation of an inwardly rectifying potassium conductance by muscarinic receptor stimulation was studied in the AtT-20 pituitary cell line, using the whole-cell patch-clamp technique. Only m4 mRNA was detected in these cells, thus, it is assumed that the actions of muscarinic receptor stimulation are mediated by the m4 receptor. AtT-20 cells express a slowly activating inwardly rectifying potassium conductance. Application of acetylcholine (ACh), resulted in an atropine sensitive, reversible increase in inwardly rectifying current. The ACh-induced current differed from the current recorded in control, in that it was fast activating, while the control current was slowly activating. Inclusion of GTP gamma S in the patch pipette activated an inward current with characteristics similar to the ACh-induced current, and the ACh-induced current response could be inhibited by pre-incubation with pertussis toxin (PTX). It is concluded that the m4 muscarinic receptor is coupled to an inwardly rectifying potassium conductance via a PTX sensitive G-protein.", "contents": "m4 muscarinic receptor subtype activates an inwardly rectifying potassium conductance in AtT20 cells. The modulation of an inwardly rectifying potassium conductance by muscarinic receptor stimulation was studied in the AtT-20 pituitary cell line, using the whole-cell patch-clamp technique. Only m4 mRNA was detected in these cells, thus, it is assumed that the actions of muscarinic receptor stimulation are mediated by the m4 receptor. AtT-20 cells express a slowly activating inwardly rectifying potassium conductance. Application of acetylcholine (ACh), resulted in an atropine sensitive, reversible increase in inwardly rectifying current. The ACh-induced current differed from the current recorded in control, in that it was fast activating, while the control current was slowly activating. Inclusion of GTP gamma S in the patch pipette activated an inward current with characteristics similar to the ACh-induced current, and the ACh-induced current response could be inhibited by pre-incubation with pertussis toxin (PTX). It is concluded that the m4 muscarinic receptor is coupled to an inwardly rectifying potassium conductance via a PTX sensitive G-protein."} {"id": "PMID:1283454", "title": "Suppression of a calcium current by CNQX and kynurenate.", "content": "During our investigation of a sustained high voltage-activated (HVA) calcium current in retinal horizontal cells, we found that the glutamate receptor antagonists CNQX and kynurenate but not AP7 reversibly reduced the peak amplitude of the HVA current. Changes in the HVA current kinetics or activation voltage were not apparent; there was only a reduction in the peak current. The novel effects of these antagonists on HVA calcium currents reported here could have an impact on many studies involving glutamatergic synaptic transmission.", "contents": "Suppression of a calcium current by CNQX and kynurenate. During our investigation of a sustained high voltage-activated (HVA) calcium current in retinal horizontal cells, we found that the glutamate receptor antagonists CNQX and kynurenate but not AP7 reversibly reduced the peak amplitude of the HVA current. Changes in the HVA current kinetics or activation voltage were not apparent; there was only a reduction in the peak current. The novel effects of these antagonists on HVA calcium currents reported here could have an impact on many studies involving glutamatergic synaptic transmission."} {"id": "PMID:1283455", "title": "Suppression of a ligand operated membrane current by the epileptogenic agent pentylenetetrazol in oocytes of Xenopus laevis after injection of rat brain RNA.", "content": "The effects of the epileptogenic substance pentylenetetrazol (PTZ) on ligand operated membrane channels were studied. For this purpose serotonin (5-HT) sensitive channels were expressed in RNA injected oocytes of Xenopus laevis. With simultaneous application of both substances, the response to 5-HT was reduced and eventually abolished by PTZ with increasing concentrations (5-100 mM). A reduction of the 5-HT response also appeared when PTZ was applied in various intervals (15 and 240 s) before 5-HT. It may be assumed that PTZ produces a component of its epileptogenic effect by acting on ligand operated membrane channels.", "contents": "Suppression of a ligand operated membrane current by the epileptogenic agent pentylenetetrazol in oocytes of Xenopus laevis after injection of rat brain RNA. The effects of the epileptogenic substance pentylenetetrazol (PTZ) on ligand operated membrane channels were studied. For this purpose serotonin (5-HT) sensitive channels were expressed in RNA injected oocytes of Xenopus laevis. With simultaneous application of both substances, the response to 5-HT was reduced and eventually abolished by PTZ with increasing concentrations (5-100 mM). A reduction of the 5-HT response also appeared when PTZ was applied in various intervals (15 and 240 s) before 5-HT. It may be assumed that PTZ produces a component of its epileptogenic effect by acting on ligand operated membrane channels."} {"id": "PMID:1283456", "title": "Tunicamycin-induced inhibition of functional expression of glutamate receptors in Xenopus oocytes.", "content": "The effects of tunicamycin, a specific inhibitor of N-linked glycosylation, on functional expression of glutamate receptor subtypes were investigated in RNA-injected oocytes. In the presence of tunicamycin the expression of ligand-operated receptors sensitive to kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate were completely blocked. The inhibitory effect was reversible after removal of tunicamycin from the culture medium.", "contents": "Tunicamycin-induced inhibition of functional expression of glutamate receptors in Xenopus oocytes. The effects of tunicamycin, a specific inhibitor of N-linked glycosylation, on functional expression of glutamate receptor subtypes were investigated in RNA-injected oocytes. In the presence of tunicamycin the expression of ligand-operated receptors sensitive to kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate were completely blocked. The inhibitory effect was reversible after removal of tunicamycin from the culture medium."} {"id": "PMID:1283457", "title": "Aminooxyacetic acid causes selective neuronal loss in layer III of the rat medial entorhinal cortex.", "content": "Aminooxyacetic acid (AOAA) was used to produce a selective lesion in the rat entorhinal cortex (EC). As assessed 7 days following the injection of AOAA (75 micrograms/0.75 microliter) into the EC, neuronal loss in layer III of the medial EC, particularly in its ventral portion, was consistently observed in Nissl-stained horizontal sections. This selective neurodegeneration was seen even when AOAA was injected laterally or in deeper layers. Behavioral seizures occurred between 2 and 4 h after the AOAA injection. AOAA-induced EC lesions may provide experimental models for the study of human diseases in which the EC, particularly layer III neurons, is involved.", "contents": "Aminooxyacetic acid causes selective neuronal loss in layer III of the rat medial entorhinal cortex. Aminooxyacetic acid (AOAA) was used to produce a selective lesion in the rat entorhinal cortex (EC). As assessed 7 days following the injection of AOAA (75 micrograms/0.75 microliter) into the EC, neuronal loss in layer III of the medial EC, particularly in its ventral portion, was consistently observed in Nissl-stained horizontal sections. This selective neurodegeneration was seen even when AOAA was injected laterally or in deeper layers. Behavioral seizures occurred between 2 and 4 h after the AOAA injection. AOAA-induced EC lesions may provide experimental models for the study of human diseases in which the EC, particularly layer III neurons, is involved."} {"id": "PMID:1283458", "title": "1,10-Diaminodecane and 1,12-diaminododecane block NMDA receptor currents by an open channel mechanism.", "content": "In whole-cell recordings from cultured rat hippocampal neurons (VH = -60 mV), 1,10-diaminodecane (DA10) and 1,12-diaminododecane (DA12) produced a concentration-dependent block of NMDA-induced current (IC50 = 30 and 7 microM, resp.). In contrast, the diamines failed to affect AMPA and kainate currents. The inhibition of NMDA currents was highly voltage-dependent and was substantially relieved at positive holding potentials. In outside-out patches, DA10 and DA12 produced a voltage-dependent flickery block of NMDA-activated single-channel currents. These results indicate that DA10 and DA12 antagonize NMDA responses via an open channel mechanism. DA10 and DA12 have been proposed to be inverse agonists at the spermine facilitatory site on the NMDA receptor. However, the channel blocking effects of the diamines complicate the interpretation of their actions at this site.", "contents": "1,10-Diaminodecane and 1,12-diaminododecane block NMDA receptor currents by an open channel mechanism. In whole-cell recordings from cultured rat hippocampal neurons (VH = -60 mV), 1,10-diaminodecane (DA10) and 1,12-diaminododecane (DA12) produced a concentration-dependent block of NMDA-induced current (IC50 = 30 and 7 microM, resp.). In contrast, the diamines failed to affect AMPA and kainate currents. The inhibition of NMDA currents was highly voltage-dependent and was substantially relieved at positive holding potentials. In outside-out patches, DA10 and DA12 produced a voltage-dependent flickery block of NMDA-activated single-channel currents. These results indicate that DA10 and DA12 antagonize NMDA responses via an open channel mechanism. DA10 and DA12 have been proposed to be inverse agonists at the spermine facilitatory site on the NMDA receptor. However, the channel blocking effects of the diamines complicate the interpretation of their actions at this site."} {"id": "PMID:1283459", "title": "Nitric oxide synthase immunoreactivity in rat spinal cord.", "content": "Immunoreactivity to nitric oxide synthase (NOS-IR) and choline acetyltransferase (ChAT-IR) was detected in the adult rat spinal cord using the avidin-biotin-peroxidase technique. Intensely stained NOS-positive neurons with cell processes were observed in the intermediolateral cell column of the thoracic and sacral segments and around the central canal of all segments. These areas also contained ChAT-IR neurons. A number of small- to medium-sized NOS-IR cells were noted in the superficial and deeper laminae throughout the entire cord. NOS-IR was not detected in the ventral horn motoneurons, which were, however, ChAT-IR. The results indicate that NOS-IR is present in autonomic preganglionic neurons and in selected neurons in the dorsal horn and lamina X, but appears to be absent in motoneurons.", "contents": "Nitric oxide synthase immunoreactivity in rat spinal cord. Immunoreactivity to nitric oxide synthase (NOS-IR) and choline acetyltransferase (ChAT-IR) was detected in the adult rat spinal cord using the avidin-biotin-peroxidase technique. Intensely stained NOS-positive neurons with cell processes were observed in the intermediolateral cell column of the thoracic and sacral segments and around the central canal of all segments. These areas also contained ChAT-IR neurons. A number of small- to medium-sized NOS-IR cells were noted in the superficial and deeper laminae throughout the entire cord. NOS-IR was not detected in the ventral horn motoneurons, which were, however, ChAT-IR. The results indicate that NOS-IR is present in autonomic preganglionic neurons and in selected neurons in the dorsal horn and lamina X, but appears to be absent in motoneurons."} {"id": "PMID:1283460", "title": "Evidence that CHP100 neuroblastoma cell death induced by N-methyl-D-aspartate involves L-arginine-nitric oxide pathway activation.", "content": "Evidence suggests that nitric oxide (NO) may mediate, at least in part, excitotoxic effects of excessive N-methyl-D-aspartate (NMDA) receptor activation both in vivo and in vitro. In the present experiments, NMDA-induced excitotoxicity has been studied in CHP100 neuroblastoma cell cultures. Application of NMDA (0.25-1.5 mM) produced concentration-dependent cell death. These effects were antagonized by co-application of dizocilpine (MK801), a selective and non-competitive NMDA receptor complex antagonist. Protection from NMDA-induced lethal effects was also afforded by N omega-nitro-L-arginine methyl ester, a potent NO-synthase inhibitor, and by hemoglobin, a NO-trapping agent. In addition, substitution of L-arginine, normally present in the exposure solution with its D-isomer, abolished the cell death induced by the excitotoxin. In conclusion, the present experiments support the suggestion that excitotoxic effects induced by NMDA receptor stimulation involve L-arginine-NO pathway activation.", "contents": "Evidence that CHP100 neuroblastoma cell death induced by N-methyl-D-aspartate involves L-arginine-nitric oxide pathway activation. Evidence suggests that nitric oxide (NO) may mediate, at least in part, excitotoxic effects of excessive N-methyl-D-aspartate (NMDA) receptor activation both in vivo and in vitro. In the present experiments, NMDA-induced excitotoxicity has been studied in CHP100 neuroblastoma cell cultures. Application of NMDA (0.25-1.5 mM) produced concentration-dependent cell death. These effects were antagonized by co-application of dizocilpine (MK801), a selective and non-competitive NMDA receptor complex antagonist. Protection from NMDA-induced lethal effects was also afforded by N omega-nitro-L-arginine methyl ester, a potent NO-synthase inhibitor, and by hemoglobin, a NO-trapping agent. In addition, substitution of L-arginine, normally present in the exposure solution with its D-isomer, abolished the cell death induced by the excitotoxin. In conclusion, the present experiments support the suggestion that excitotoxic effects induced by NMDA receptor stimulation involve L-arginine-NO pathway activation."} {"id": "PMID:1283461", "title": "Distribution of NADPH-diaphorase-positive nerves in the uterine cervix and neurons in dorsal root and paracervical ganglia of the female rat.", "content": "Nitric oxide synthase (NOS) was selectively stained in nerve fibers of the uterine cervix and neurons of the paracervical (PG) and dorsal root ganglia (DRG) by NADPH diaphorase histochemistry. In the cervix, numerous NADPH-diaphorase-positive nerve fibers were observed in the myometrium, endometrium and around arteries. In addition, a subpopulation of neurons within ganglia that innervate the cervix, i.e., the PG and DRG, were NADPH-diaphorase positive; thus the fibers in the cervix could be sensory and/or autonomic. NADPH-diaphorase/NOS localization identifies sites where nitric oxide (NO) can be synthesized. Since NO relaxes vascular and nonvascular smooth muscle, the prevalence and anatomical localization of NADPH-diaphorase-positive fibers suggest that they could influence functions of the uterine cervix.", "contents": "Distribution of NADPH-diaphorase-positive nerves in the uterine cervix and neurons in dorsal root and paracervical ganglia of the female rat. Nitric oxide synthase (NOS) was selectively stained in nerve fibers of the uterine cervix and neurons of the paracervical (PG) and dorsal root ganglia (DRG) by NADPH diaphorase histochemistry. In the cervix, numerous NADPH-diaphorase-positive nerve fibers were observed in the myometrium, endometrium and around arteries. In addition, a subpopulation of neurons within ganglia that innervate the cervix, i.e., the PG and DRG, were NADPH-diaphorase positive; thus the fibers in the cervix could be sensory and/or autonomic. NADPH-diaphorase/NOS localization identifies sites where nitric oxide (NO) can be synthesized. Since NO relaxes vascular and nonvascular smooth muscle, the prevalence and anatomical localization of NADPH-diaphorase-positive fibers suggest that they could influence functions of the uterine cervix."} {"id": "PMID:1283462", "title": "Neonatal capsaicin treatment prevents the development of the thermal hyperalgesia produced in a model of neuropathic pain in the rat.", "content": "Loose ligation of the sciatic nerve with 4-0 chromic gut sutures in rats produces behavioral evidence of neuropathic pain. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating the thermal hyperalgesia produced by this model. Male Sprague-Dawley rats, treated as neonates (within 48 h of birth) with capsaicin (50 mg/kg, s.c.) or vehicle, were used at 16-18 weeks of age. Chromic gut sutures (4-0) were tied around the left sciatic nerve and withdrawal latencies of both hind paws to radiant heat were determined on postoperative days 3, 5, 10 and 20. Whereas there was a pronounced thermal hyperalgesia which lasted for up to 20 days in vehicle-treated rats, there was no evidence of thermal hyperalgesia in capsaicin-treated rats. There was no difference in baseline (pre-surgery) withdrawal latencies between the two groups. Radioimmunoassay revealed that there was a significant depletion of substance P (43.8%) and calcitonin-gene-related peptide (72.6%) in the lumbar spinal cord of neonatal capsaicin-treated rats compared to vehicle-treated rats. These results demonstrate that the chromic gut-induced thermal hyperalgesia is mediated by capsaicin-sensitive afferents and suggest that central mechanisms which process and control the reflex response to heat are different than mechanisms involved in thermal hyperalgesia.", "contents": "Neonatal capsaicin treatment prevents the development of the thermal hyperalgesia produced in a model of neuropathic pain in the rat. Loose ligation of the sciatic nerve with 4-0 chromic gut sutures in rats produces behavioral evidence of neuropathic pain. In the present experiments we examined the involvement of capsaicin-sensitive afferents in mediating the thermal hyperalgesia produced by this model. Male Sprague-Dawley rats, treated as neonates (within 48 h of birth) with capsaicin (50 mg/kg, s.c.) or vehicle, were used at 16-18 weeks of age. Chromic gut sutures (4-0) were tied around the left sciatic nerve and withdrawal latencies of both hind paws to radiant heat were determined on postoperative days 3, 5, 10 and 20. Whereas there was a pronounced thermal hyperalgesia which lasted for up to 20 days in vehicle-treated rats, there was no evidence of thermal hyperalgesia in capsaicin-treated rats. There was no difference in baseline (pre-surgery) withdrawal latencies between the two groups. Radioimmunoassay revealed that there was a significant depletion of substance P (43.8%) and calcitonin-gene-related peptide (72.6%) in the lumbar spinal cord of neonatal capsaicin-treated rats compared to vehicle-treated rats. These results demonstrate that the chromic gut-induced thermal hyperalgesia is mediated by capsaicin-sensitive afferents and suggest that central mechanisms which process and control the reflex response to heat are different than mechanisms involved in thermal hyperalgesia."} {"id": "PMID:1283464", "title": "Purification and characterization of the major cationic kallikrein inhibitor in bovine pituitary gland.", "content": "The presence of two types of kallikrein inhibitor (cationic and anionic inhibitors) was demonstrated in bovine pituitary gland. These kallikrein inhibitors were separated from the homogenate of bovine posterior pituitary by successive CM-Sephadex chromatography. The major cationic inhibitor was further purified to homogeneity by affinity chromatography using porcine pancreatic beta-kallikrein immobilized on Sepharose 4B and gel filtration. The complete amino acid sequence of this inhibitor was first determined, and it was shown to be a peptide of 58 residues with a calculated molecular weight of 6,511. The Ki value against bovine pituitary kallikrein was 6 x 10(-9) M. The cationic inhibitor was found to be identical with basic pancreatic trypsin inhibitor.", "contents": "Purification and characterization of the major cationic kallikrein inhibitor in bovine pituitary gland. The presence of two types of kallikrein inhibitor (cationic and anionic inhibitors) was demonstrated in bovine pituitary gland. These kallikrein inhibitors were separated from the homogenate of bovine posterior pituitary by successive CM-Sephadex chromatography. The major cationic inhibitor was further purified to homogeneity by affinity chromatography using porcine pancreatic beta-kallikrein immobilized on Sepharose 4B and gel filtration. The complete amino acid sequence of this inhibitor was first determined, and it was shown to be a peptide of 58 residues with a calculated molecular weight of 6,511. The Ki value against bovine pituitary kallikrein was 6 x 10(-9) M. The cationic inhibitor was found to be identical with basic pancreatic trypsin inhibitor."} {"id": "PMID:1283465", "title": "Immunohistochemical localization of PGF2 alpha receptor in the mouse testis.", "content": "As a step towards understanding the role of prostaglandin F2 alpha (PGF2 alpha) in male reproductive tract physiology, a rabbit polyclonal antiserum reactive with purified PGF2 alpha receptor (PGF2 alpha-R) was produced. Here we describe the use of this anti-PGF2 alpha-R antiserum in immunohistochemical staining of mouse testis to ascertain which cell types, in vivo, possess immunoreactive PGF2 alpha-R. As an initial control Western blot analysis was performed to show that the anti-PGF2 alpha-R antiserum recognizes only one antigen in the testis, and that this molecule is similar in molecular mass (by PAGE) to the previously described, purified PGF2 alpha-R molecule. Immunohistochemical staining demonstrates that adult mouse testis contains a single subpopulation of cells with PGF2 alpha-R and that subpopulation is the interstitial or Leydig cell subpopulation. Cell and tissue types negative for immunoreactive PGF2 alpha-R include: the capsule (tunica albuginea) and subcapsular stroma, all histologic layers of the vasculature (both venules and arterioles), peritubular stroma, peritubular boundary tissue, spermatogonia, primary and secondary spermatocytes, spermatids, Sertoli cells, and spermatozoa. While the above described localization of PGF2 alpha-R is also seen in rat, there are fewer rat Leydig cells and this subpopulation appears to atrophy and stain less intensely with increasing age of the animal. Preabsorption of the PGF2 alpha-R antiserum with a corpora lutea homogenate acetone powder eliminated immunohistochemical staining of the Leydig cell subpopulation further suggesting that the antigenic determinant detected here is related to that in the ovary (PGF2 alpha-R).", "contents": "Immunohistochemical localization of PGF2 alpha receptor in the mouse testis. As a step towards understanding the role of prostaglandin F2 alpha (PGF2 alpha) in male reproductive tract physiology, a rabbit polyclonal antiserum reactive with purified PGF2 alpha receptor (PGF2 alpha-R) was produced. Here we describe the use of this anti-PGF2 alpha-R antiserum in immunohistochemical staining of mouse testis to ascertain which cell types, in vivo, possess immunoreactive PGF2 alpha-R. As an initial control Western blot analysis was performed to show that the anti-PGF2 alpha-R antiserum recognizes only one antigen in the testis, and that this molecule is similar in molecular mass (by PAGE) to the previously described, purified PGF2 alpha-R molecule. Immunohistochemical staining demonstrates that adult mouse testis contains a single subpopulation of cells with PGF2 alpha-R and that subpopulation is the interstitial or Leydig cell subpopulation. Cell and tissue types negative for immunoreactive PGF2 alpha-R include: the capsule (tunica albuginea) and subcapsular stroma, all histologic layers of the vasculature (both venules and arterioles), peritubular stroma, peritubular boundary tissue, spermatogonia, primary and secondary spermatocytes, spermatids, Sertoli cells, and spermatozoa. While the above described localization of PGF2 alpha-R is also seen in rat, there are fewer rat Leydig cells and this subpopulation appears to atrophy and stain less intensely with increasing age of the animal. Preabsorption of the PGF2 alpha-R antiserum with a corpora lutea homogenate acetone powder eliminated immunohistochemical staining of the Leydig cell subpopulation further suggesting that the antigenic determinant detected here is related to that in the ovary (PGF2 alpha-R)."} {"id": "PMID:1283466", "title": "The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver.", "content": "In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect.", "contents": "The effect of iloprost and NDGA in ischemia reperfusion injury in rat liver. In this study, the effects of iloprost (ZK 36374) and NDGA on warm ischemia and reperfusion injury in rat liver were investigated. Rats were given isotonic saline (control group), iloprost 25 micrograms/kg i.v. (group II) just before warm ischemia or NDGA 10 micrograms/kg i.v. (group III) 5 min before reperfusion or the same drugs were given together (group IV). Serum SGOT, SGPT, and LDH values and tissue malondialdehyde (MDA), glutathione (GSH), prostaglandin (PG)E2, and leukotriene (LT)C4 levels were determined after ischemia-reperfusion injury. Histopathologic examination of the liver was carried out under the light microscope. The serum SGOT, SGPT and LDH levels improved significantly in groups II, III, and IV when compared with the control group (p < 0.05). There was a significant decrease (p < 0.05) in tissue MDA levels and significant increase (p < 0.05) in tissue GSH levels in group I, when compared with group IV and the control groups. The values did not differ significantly in group IV when compared to controls. The LTC4/PGE2 ratio was low and histologic findings were worse in group III. In conclusion, iloprost was found to be beneficial in preventing the ischemia-reperfusion injury in the rat livers. NDGA, either by direct toxic effect or by shifting the arachidonic acid metabolism to the cyclooxygenase route, was not found to be as effective. Iloprost and NDGA did not exert a synergist effect."} {"id": "PMID:1283467", "title": "Recent National Cancer Institute lymphoma trials of etoposide-containing combination chemotherapy.", "content": "Short-course prednisone/doxorubicin/cyclophospha- mide/etoposide-cytarabine/bleomycin/vincristine/methotrexate (ProMACE-CytaBOM) contains the same drugs as standard ProMACE-CytaBOM but is delivered weekly for 16 weeks rather than 2 weeks out of 3 for 18 weeks. This results in a significant increase in dose intensity, ranging from 27% to 65% for all drugs. A total of 46 patients have been treated with short-course ProMACE-CytaBOM. The overall complete response rate of 91% and relapse rate of 17% compares favorably with results obtained using standard ProMACE-CytaBOM (86% and 27%, respectively). Toxicity was slightly greater with short-course therapy, but in general the regimen was well tolerated. Further dose intensification is possible in eligible patients by dose escalating myelotoxic drugs. A second strategy for augmenting the dose intensity is to deliver the drugs by continuous intravenous infusion. Infusional chemotherapy with doxorubicin/etoposide/vincristine/oral prednisone/bolus cyclophosphamide (EPOCH) results in significant antitumor activity in heavily pretreated patients with chemotherapy-resistant Hodgkin's disease and non-Hodgkin's lymphomas. Complete responses or partial responses were seen in 91% of 21 evaluable patients.", "contents": "Recent National Cancer Institute lymphoma trials of etoposide-containing combination chemotherapy. Short-course prednisone/doxorubicin/cyclophospha- mide/etoposide-cytarabine/bleomycin/vincristine/methotrexate (ProMACE-CytaBOM) contains the same drugs as standard ProMACE-CytaBOM but is delivered weekly for 16 weeks rather than 2 weeks out of 3 for 18 weeks. This results in a significant increase in dose intensity, ranging from 27% to 65% for all drugs. A total of 46 patients have been treated with short-course ProMACE-CytaBOM. The overall complete response rate of 91% and relapse rate of 17% compares favorably with results obtained using standard ProMACE-CytaBOM (86% and 27%, respectively). Toxicity was slightly greater with short-course therapy, but in general the regimen was well tolerated. Further dose intensification is possible in eligible patients by dose escalating myelotoxic drugs. A second strategy for augmenting the dose intensity is to deliver the drugs by continuous intravenous infusion. Infusional chemotherapy with doxorubicin/etoposide/vincristine/oral prednisone/bolus cyclophosphamide (EPOCH) results in significant antitumor activity in heavily pretreated patients with chemotherapy-resistant Hodgkin's disease and non-Hodgkin's lymphomas. Complete responses or partial responses were seen in 91% of 21 evaluable patients."}